• Academician General Victor Voicu at the anniversary
• Effect of the selective serotonin re-uptake inhibitors over coagulation in patients with depressive disorders – a systematic review and
retrospective analysis
• Improved methodology of using simulators develops better practical skills in laparoscopy of future residents
• Current review of surgical management options for rotational alignment of the femoral and tibial component in total knee replacement
• The risk of bioterrorist and biocrime attack in the contemporary world
• The concept of biological warfare and real biological attacks
• Morphological characteristics of the celiac-mesenteric trunk
• Local treatment options for management of loco-regional esophageal squamous cell carcinoma
• Methods of assessing stable coronary artery disease by non-invasive imaging techniques
• Endoscopic eradication of nodular gastric vascular antral ectasia by using band ligation after argon plasma coagulation
• Death due to a rare posttraumatic complication: fat embolism
• Papillary thyroid carcinoma arising on a hypertrofic pyramidal lobe
• Atypical Cogan syndrome; case report
• Patient-physician communication, an essential condition for an effective medical act
• The tree we generally throw stones at
www.revistamedicinamilitara.ro
Founded 1897 • New Series
Vol. CXXII • No. 2/2019 • August
REVISTA DE MEDICINĂ MILITARĂ
Military Medicine
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Editorial Board of Romanian Journal of Military Medicine
Under the patronage Romanian Association of Military Physicians and Pharmacists Carol Davila University of Medicine and Pharmacy, Bucharest, Romania
Honorary Editor Acad. Victor Voicu MD, PhD
Editors-in-Chief Florentina Ioniță Radu MD, PhD, MBA Dan Mischianu MD, PhD
Executive Editors Daniel O. Costache MD, PhD, MBA Victor L. Purcărea PhD, MBA
Associate Editor Mariana Jinga MD, PhD, MBA
Redactors Raluca S. Costache MD, PhD, MBA – Bucharest Mihail S. Tudosie MD, PhD – Bucharest
Editorial Assistants Ioana Bratu MD Cristina Solea
Technical Secretary Oana Ciobanu Ionuț M. Olteanu
Publisher Carol Davila University of Medicine and Pharmacy Publishing House
International Editorial Board
Natan Børnstein (Israel) Silviu Brill (Israel)
Cris S. Constantinescu (UK) Daniel Dănilă (USA)
Stergios Ganatsios (Greece)
Mihai Moldovan (Denmark) Ioan Opriș (USA)
Gerard Roul (France) Erwin Santo (Israel)
Adrian Săftoiu (Denmark) Ioanel Sinescu (Romania)
C. Ionescu Târgovişte (Romania) Radu Ţuţuian (Switzerland) Shyam Varadarajulu (USA) Peter Vilmann (Denmark)
Victor Voicu (Romania)
Scientific Publishing Committee
Adrian Barbilian (Bucharest) Anda Băicuş (Bucharest)
Cristian Băicuş (Bucharest) Andra R. Bălănescu (Bucharest)
Mircea Beuran (Bucharest) Ovidiu Bratu (Bucharest)
Daciana Brănișteanu (Iași) Dragoș Bumbăcea (Bucharest)
Marian Burcea (Bucharest) Sofia Colesca (Bucharest)
Gabriel Constantinescu (Bucharest) Silviu Constantinoiu (Bucharest)
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Romanian Journal of Military Medicine, New Series, vol. CXXII, No 2/2019, August
ISSN-L 1222-5126; eISSN 2501-2312; pISSN 1222-5126
1
Founded 1897 • New Series
Vol. CXXII • No. 2/2019 • August
Edited by the Romanian Association of Military Physicians and Pharmacists.
Contents
EDITORIAL
*** ● Academician General Victor Voicu at the anniversary 5
SYSTEMATIC REVIEW
Octavian Vasiliu ● Effect of the selective serotonin reuptake inhibitors over coagulation in patients with depressive disorders – a systematic review and retrospective analysis 7
REVIEW ARTICLE
Cristian V. Toma, Cristian S. Sima, Daniel G. Radavoi, Traian Constantin, Daniel L. Bădescu, Viorel Jinga ● Improved methodology of using simulators develops better practical skills in laparoscopy of future residents 12
Bogdan Crețu, Cătălin Cîrstoiu, Ștefan Cristea ● Current review of surgical management options for rotational alignment of the femoral and tibial component in total knee replacement 16
ORIGINAL ARTICLES
Ioana A. Gal, Teodora B. Eremia, Mihail S. Tudosie, Viorel Ordeanu ● The risk of bioterrorist and biocrime attack in the contemporary world 21
Teodora B. Eremia, Ioana A. Gal, Iulia M. Staicu, Mihail S. Tudosie, Viorel Ordeanu ● The concept of biological warfare and real biological attacks 26
P. Bordei, R. Baz, V. Rusali, Cristian R. Jecan, V. Ardeleanu ● Morphological characteristics of the celiac-mesenteric trunk 31
Tülay Eren ● Local treatment options for management of loco-regional esophageal squamous cell carcinoma 36
Carmen M. Voicu, Tiberiu Nanea ● Methods of assessing stable coronary artery disease by non-invasive imaging techniques 43
CLINICAL PRACTICE
Săndica Bucurică, Mihaela Ailenei, Mariana Jinga, Florentina Ioniță Radu ● Endoscopic eradication of nodular gastric vascular antral ectasia by using band ligation after argon plasma coagulation 51
RJMM Romanian Journal of Military Medicine
2
Cristina Podilă, Mihaela C. Șomlea, Bogdan A. Buhaș, Adrian S. Judea, Andreea A. Hleșcu, Nicolae Nicoară, Flavia Săndoiu, Paula Marian, Bianca Hanganu, Irina S. Manoilescu ● Death due to a rare posttraumatic complication: fat embolism 56
Rodica Petriș, Ionuț B. Sandu, Adina Dragomir, Dumitru Ioachim, Cristina Iosif, Ruxandra Dănciulescu-Miulescu, Alexandra Mirică, Diana Păun ● Papillary thyroid carcinoma arising on a hypertrofic pyramidal lobe 62
Gabriela C. Mușat, Roxana E. Decusară, Ovidiu Mușat ● Atypical Cogan syndrome; case report 66
VARIA
Carmen M. Voicu, Consuela M. Gheorghe ● Patient-physician communication, an essential condition for an effective medical act 73
Mihail Mihailide ● The tree we generally throw stones at 77
Guidelines for authors 85
Vol. CXXII • No. 2/2019 • August • Romanian Journal of Military Medicine
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4
Vol. CXXII • No. 2/2019 • August • Romanian Journal of Military Medicine
5
EDITORIAL
Academician General Victor Voicu at the anniversary
An anniversary is rather meant to reflect on the past, present
and future, being at the same time, and a reason for
celebration.
On Wednesday, June 26, 2019, the book of Academician
Victor Voicu – "Under the sign of Hippocrates" was released
in the Auditorium of the Romanian Academy – a book
recently published by the prestigious European Idea
Publishing House. It was a moment of great and wonderful
celebration.
We will only remind you the essential things about
Academician General Victor Voicu – a distinguished and
emblematic personality of civil and military medicine (in the
context in which the assertion of civilian physician – military
physician is increasingly obsolete) from our country.
Born June 29, 1939 in the village of Bolovani, Dambovita
county, student of "St. Sava" National College in Bucharest,
transferred in the last year to "Ştefan cel Mare" Military
Highschool in Iaşi (currently in Câmpulung Moldovenesc) –
the moment when he put on the military coat, selected from
the best for the Medical-Military Institute, the Faculty of
Medicine – Medical Pharmace-utical Institute in Bucharest,
which he graduated in 1962, apparently we would not have
too much to say... and yet!
He chooses pharmacology and clinical pharmacology and the
intuition of his master, Alfred Teitel, imposes the future cre-
ator of the School of Pharma-cology, Toxicology and Psycho-
pharmacology from our country.
University Assistant, starting from 1966 Scientific Researcher
at the Radiobiology and Molecular Biology Center, since
1972 Associate Professor and Head of the Pharmacology
Department of the recently established Faculty of Medicine
from Craiova, since 1990 Professor of Pharmacology,
Toxicology and Psychopharmacology at the University of
Medicine and Pharmacy "Carol Davila", Head of the Medical
Department of the Ministry of National Defense between
1990-1995, Commander of the Medical-Military Scientific
Research Center for 26 years (1987-2013), Corresponding
Member (1991) and Full member (2001) of the Romanian
Academy, Secretary-General in two legislatures and Vice-
President of this High Authority from April 2018.
6
The life, work, efforts and achievements of a MAN cannot be
reduced only to the previous sentence. Those who want to
learn more about the frankness and the visionary spirit of
Academician Victor Voicu, can do that by making use of
"search engines", as they say nowadays.
Academician Nicolae Breban enlightened the thoughts of the
audience when he pronounced the word "energetic", adding
it to the joy felt by those present at the release of the book I
previously mentioned.
General Academician Victor Voicu, a descendent in time of
our common ancestor - General physician and pharmacist
Academician p.m. (2003) Carol Davila is not only an
"energetic" man, but also an "energetic" spirit for those
around him, for all of us, when through his vision, calm and
analytical spirit, he manages to clarify things and "indicate"
the right direction to follow.
The release of the book, "Under the Sign of Hippocrates,"
was for all participants, as well as for future readers, a
celebration of the spirit.
The editorial staff of the
Romanian Journal of Military Medicine
Wishes
Happy Birthday!
To
Academician Victor Voicu
Honorary Editor
Vol. CXXII • No. 2/2019 • August • Romanian Journal of Military Medicine
7
Article received on February 21, 2019 and accepted for publishing on June 11, 2019.
SYSTEMATIC REVIEW
Effect of the selective serotonin reuptake inhibitors over coagulation in patients with depressive disorders – a systematic review and retrospective analysis
Octavian Vasiliu1
Abstract: Several problems related to coagulation dysfunctions induced by selective serotonin reuptake inhibitors (SSRIs) were reported in literature, as serotonin is widely distributed in the human organism and it has significant contribution in various vascular and hematologic regulatory mechanisms. First, a systematic review has integrated main results from the field of SSRIs and anticoagulants pharmacologic interactions. Secondly, a retrospective analysis was performed, based on the medical charts of hospitalized patients diagnosed with SSRI-treated depressive disorders, who also received concomitant anticoagulant treatment with acenocoumarol. Platelet count, prothrombin time, activated partial thromboplastin time, and bleeding time were monitored during hospitalization and their values before and after SSRI initiation treatment were compared.
Keywords: major depressive disorder, antidepressants, anticoagulants, serotonin
CURRENT STAGE OF RESEARCH IN THE FIELD OF SSRIs-
ANTICOAGULANTS INTERACTIONS AND SSRIs-INDUCED
COAGULATION DYSFUNCTIONS
Data in the literature regarding selective serotonin reuptake
inhibitors (SSRI) treatment in patients diagnosed with
depressive disorders and cardiovascular pathology for which
they receive anticoagulants contain contradictions regarding
the magnitude of antidepressants’ effect over coagulation
parameters.
Currently available informations suggest the existence of a
decrease in platelets serotonin due to serotoninergic
antidepressants action, and this phenomenon appears to be
explained by a pharmacogenetic mechanism, through
serotonin transporter promotor gene (5-HTTLPR) poly-
morphism [1, 2]. Also, it has been observed that serotonin-
nergic antidepressants could mitigate the depression- and
anxiety-related procoagulant action [3], while yet another
studies reveal the lack of significant effect of sertraline over
coagulation in patients after an acute myocardial infarction
[4].
An independent analysis of clinical trials published in the
main electronic databases (PubMed, Cochrane, Medscape,
and EMBASE), using keywords “anti-depressant”, “serotonin
selective reuptake inhibitors”, “major depressive disorder
(MDD)”, “coagulation”, “anticoagulants”, “paroxetine”, ”ser-
traline”, “escitalopram”, “citalopram”, “fluoxetine”, “fluvo-
xamine”, “warfarine”, and “acenocoumarol” was performed.
Only articles published between 1996 and 2018 have been
selected.
Specific inclusion and exclusion criteria had been formulated
according to Table 1.
1 Dr. Carol Davila University Central Emergency Military Hospital, Bucharest, Romania
Corresponding author: Octavian Vasiliu MD
8
Table 1. Selection criteria for literature research
Operationalized criteria Inclusion criteria Exclusion criteria
Population Inferior age limit is 18, no superior limit had been esta-blished. Diagnoses of MDD, dysthymia, adjustment disorder with depressive features, bipolar depression, mixed depressive and anxious disorder. Diagnoses according to DSM, ICD criteria, or compatible with these classifications. Lack of substance related comorbidities.
Children and adolescents. Heterogenous populations, where statis-tical procedures didn’t allow a separate conclusion for patients aged over 18. Other disorders than those with a signi-ficant depressive component
Intervention Any agent from the SSRI class. Monitored anticoagulant treatment.
Other, non-SSRIs-antidepressants. SSRIs in combination with other anti-depressants. Concomitant use of CYP450 iso-enzymes inductors or inhibitors. Supra-therapeutic doses of SSRI agents.
Environment In-patient or out-patient. In vitro or in vivo analysis of coagulation variables.
Unspecified environment.
Primary and secondary variables
Any coagulation-related indicator, like platelet count, bleeding time, prothrombin time etc. Discontinuation of treatment due to severe adverse events from the hematological domain, like gastro-intestinal bleeding, hemorrhagic stroke etc.
Any trial without coagulation related parameters as primary variables was excluded
Design Randomized clinical trials, open-label, single-blind or double-blind, placebo-controlled or not, prospective or retrospective trials, case control studies, case reports or case series.
Unspecified design. Lack of a specific method for coagulation monitoring
Language English, French, German, Romanian Other language except for those mentioned
A number of 9 trials corresponded to these criteria and were
included in analysis. A synthetic overview of the selected
studies is presented in Table 2.
Table 2. Synthetic indicators for selected trials
Overall number of subjects
Mean duration of interaction
Age at inclusion
n=391 43.4
SD=70.9 Minimum=1
Maximum=225
n=2 7.5 weeks
SD=6.3 Minimum=3
Maximum=12
n=3 68 years old
SD=19.9 Minimum=45 Maximum=80
Due to the fact that not all of the papers published contain
complete data, synthetic indicators were calculated using
only those studies which included specified variables, like
the number of participants, mean duration of treatment or
the patients’ age at inclusion.
The most relevant research data are presented in Table 3.
SSRIs as a pharmacologic class induced lower serotonin
levels in the patients’ platelets [1] and had a significant effect
over several indicators of coagulation [3].
Fluoxetine increased significantly the bleeding time,
although not above the normal values [5]. Another trial
showed no significant influence of fluoxetine over mean
prothrombine time during warfarin treatment [6].
Escitalopram had no effect on coagulation according to one
trial [5].
Fluvoxamine could induced an over-anticoagulation status
during acenocoumarol maintenance treatment, unlike other
SSRIs used as controls [7]. Fluvoxamine effect over
coagulation is supported also by two cases treated with
warfarine [8, 9].
Sertraline is relatively safe in patients after acute MI, as it
induced no changes in bleeding time [4]. Sertraline could
interfere with warfarine at circulating binding proteins and
displaced the anticoagulant, increasing its free fraction [10].
In conclusion, escitalopram, sertraline and fluoxetine seem
to be quite safe during anticoagulant treatment, while
fluvoxamine has a tendency for inducing an over-
anticoagulation status. Not enough data have been found to
formulate a conclusion regarding paroxetine and citalopram,
but these agents seem safer than fluvoxamine, in trials who
compared various serotoninergic agents. SSRIs, as a
pharmacological class, doesn’t induce significant effects over
Vol. CXXII • No. 2/2019 • August • Romanian Journal of Military Medicine
9
coagulation from a clinical point of view.
Table 3. Studies included in the systematic review
AUTHORS DESIGN RESULTS AND OBSERVATIONS
Reikvam AG, Hustad S, Reikvam H, et al., 2012 [1]
Case-control pilot study. In vitro measurements of platelet function. N=18. Blood donors using SSRIs vs. blood donors without treatment
Donors with SSRIs had significantly lower serotonin in their thrombocytes. Coagulation could be altered in patients using SSRIs based on lower serotonin platelet concentration.
Siddiqui R, Gawande S, Shende T, et al., 2011 [5]
Prospective, open-label, diagnosis of MDD. Bleeding time, clotting time, platelet count, prothrombin time, partial thromboplastin kaolin time – all were monitored for 12 weeks. N=40. Treatment with fluoxetine or escitalopram
At week 12 a significant increase in bleeding time was detected for fluoxetine, while escitalopram had no effect on coagulation variables. Fluoxetine is more powerful inhibitor of SERT than escitalopram. Fluoxetine increased significantly the bleeding time, but not beyond the normal values
Geiser F, Conrad R, Imbierowicz K, et al., 2011 [3]
Case-control study. Anxiety and comorbid depression. APTT, fibrinogen, factor VII, factor VIII, von Willebrand factor, von Willebrand ristocetin cofactor activity, prothrombin fragment 1 and 2, thrombin-antithrombin complex, d-dimer, alpha2-antiplasmin, PAP, tissue plasminogen activator and plasminogen activator inhibitor. N=62.
Fibrinogen, plasminogen activator inhibitor, PAP differentiated SSRIs treated patients from their matched controls. After controlling for smoke status and BMI, differences between groups were significant for PAP, von Willebrand ristocetin cofactor activity and APTT. Several coagulation indicators may be affected at significant levels (p<0.05) in anxious-depressive patients treated with SSRIs
Teichert M, Visser LE, Uitterlinden AG, et al., 2011 [7]
Prospective, populational-based cohort study. INR≥6 was the event monitored in patients treated with SSRIs during acenocumarol maintenance treatment. N=225 Age ≥ 45
The risk for over-anticoagulation during acenocoumarol maintenance treatment was increased in patients treated with fluvoxamine, but not with other SSRIs. Prothrombine time in users of acenocoumarol was increased by fluvoxamine above a critical value associated with bleeding risk. Number of exposed patients to other SSRIs except for fluvoxamine was low.
Limke KK, Shelton AR, Elliott ES, 2002 [8]
Case report. Warfarin+fluvoxamine 79 year old woman
Increased values of INR that persisted for 7 days. Fluvoxamine inhibits CYP1A2, 2C9, 2C19 and 3A4, while the metabolism of warfarine involves the same isoenzimes of CYP450.
Yap KB, Low ST, 1999 [9]
Case report. Warfarin + fluvoxamine. 80 year old woman
The interaction between fluvoxamine and warfarin could persist for up to 2 weeks after stopping the antidepressant
Shapiro PA, Lesperance F, Frasure-Smith N et al., 1999 [4]
Multicenter, open-label, pilot study. MDD patients identified 5 to 30 days after admission for acute MI. Serial bleeding time determinations. N=26
Bleeding time increased in 12 patients, decreased in 4 patients, was unchanged in 2 patients, 3 patients withdraw prematurely. No significant changes in coagulation measures. Sertraline seems to be relatively safe in patients after acute MI.
Ford MA, Anderson ML, Rindone JP, Jaskar DW, 1997 [6]
Open label. Stable dose of warfarin + fluoxetine. Prothrombine time was measured during the 22 days of the trial. N=6
No significant differences in mean prothrombine time before and during fluoxetine administration were detected. Fluoxetine at 20 mg/day doesn’t influence the hypopro-thrombinemic response of warfarin.
Apseloff G, Wilner KD, Gerber N, Tremaine LM, 1997 [10]
Non-blinded, randomised, placebo-controlled. Healthy male volunteer. Warfarin+sertraline or placebo. N=12
Increased prothrombine time significantly during sertraline versus placebo (p=0.02). After 22 days a significant increase (p=0.02) in unbound warfarine was observed in sertraline vs. placebo group. Differences between groups were statistically, but not clinically significant. Sertraline has minimal effect on the CYP2C9/10 isoenzyme, while warfarin is principally mediated by this enzyme.
SERT = serotonin transporter, BMI = body mass index, APTT = activated partial thromboplastin time, PAP = plasmin-alpha2-antiplasmin complex, INR = International
Normalised Ratio, MI = myocardial infarction
10
Nevertheless, pharmacokinetic interactions between SSRIs
and anticoagulants are possible, at the plasma protein
binding level and at the CYP450 isoenzymes level, therefore
monitoring of the main coagulation parameters is
recommended in patients who undergo serotoninergic
antidepressant and anticoagulant treatment.
RETROSPECTIVE ANALYSIS IN PATIENTS USING SSRIs AND
ANTICOAGULANTS
Patients diagnosed with depressive disorders admitted in
the hospital who received an SSRI agent, and who also were
diagnosed with various cardio-vascular or hematologic
diseases for which they received anticoagulant treatment,
were analysed from coagulation parameters perspective.
Objective
To detect if significant statistical and/or clinical variation of
coagulation variables are detected during combined, SSRIs
and anticoagulant treatment.
Methods
We analyzed retrospectively charts of all patients evaluated
for depressive disorders during one year in our department
(01 January 2017 – 31 December 2017), which had anti-
coagulant treatment with acenocoumarol and also received
treatment with escitalopram, citalopram, fluoxetine,
paroxetine, fluvoxamine or sertraline. Platelet count,
prothrombin time as reflected in the INR values, APTT, and
bleeding time were analyzed in all cases which were
monitored during hospitalization and their values before and
after SSRI initiation treatment were compared.
All included patients were over 18 years old, without
previous treatment with an SSRI agent and were stabilized
on acenocoumarol at time of the admission. Depressive
disorders diagnoses were formulated according to ICD-10
criteria and included MDD, either first episode or recurrent,
bipolar depression, dysthymia, adjustment disorder with
depressive manifestations, mixed anxious-depressive
disorder.
Patients diagnosed with comorbid substance related
disorders were excluded from this analysis, and also those
with mentioned history of non-adherence to their
anticoagulation treatment.
Results
A number of 42 patients, mean age 56.6, 30 female and 12
male, diagnosed with MDD (n=23), mixed anxious-
depressive disorder (n=10), bipolar depression (n=4),
dysthymia and MDD (n=2) and adjustment disorder with
depressive manifestations (n=3) were included in the
statistical analysis. These patients had at least two
determinations of INR and platelet count in their charts and
most of them (62%) had at least 3 coagulation indicators
recorded.
Figure 1: Treatment used during anticoagulation therapy
Patients received escitalopram (n=11), citalopram (n=2),
paroxetine (n=10), sertraline (n=8), fluoxetine (n=8) or
fluvoxamine (n=3).
Figure 2: SSRIs treatment influence over coagulation indicators
(% of score variation)
No significant differences (at p<0.05) were detected in any
coagulation indicator for SSRIs as a pharmacologic class, as
reflected by t test for dependent samples, when platelet
count (p=0.166), INR (p=0.098), APTT (p=0.110), and
bleeding time (p=0.102) were analyzed pre-SSRIs
administration and after at least 7 days (mean duration of
SSRIs treatment before hospital discharge was 8.4 days).
When translated in percentage of absolute values variation,
all SSRIs changes ranged from 5 to 10% in all the monitored
parameters.
ANOVA univariate test resulted in F values ranging between
1.67 and 1.28, lower than Fcrit, at p<0.05, and η2 varied
between 0.025 and 0.069, which signifies an influence of 2.5-
6.9% of the SSRIs agent over INR, APTT, bleeding time, and
platelet count variation during acenocoumarol treatment. A
Vol. CXXII • No. 2/2019 • August • Romanian Journal of Military Medicine
11
post-hoc analysis showed a superior effect over bleeding
time for fluvoxamine over escitalopram and sertraline
(p=0.043 and 0.46), although the clinical impact of this
difference wasn’t relevant.
No significant adverse event in the hematologic area was
recorded during hospitalization period and mixed (SSRI and
anticoagulant) treatment.
Two cases (one treated with fluvoxamine 150 mg/day and
one who received paroxetine 40 mg/day) registered values
of INR above therapeutic value (5.2 and 6.1, respectively)
after 8 days of treatment, and acenocumarol doses were
adjusted.
CONCLUSIONS
SSRIs had a minor influence over main coagulation
parameters (INR, APTT, platelet count, and bleeding time)
during acenocoumarol treatment in patients with depressive
disorder and comorbid cardio-vascular or hematologic
diseases.
Fluvoxamine has been associated statistically with a lesser
safe profile than escitalopram and sertraline, although
differences in the clinical domain are not detectable.
Disclaimer
Octavian Vasiliu was speaker for Servier and Bristol-Myers, and
participated in clinical trials funded by Janssen Cilag, Astra Zeneca,
Otsuka Pharmaceuticals, Sanofi-Aventis, Sunovion Pharmaceuticals.
Ethical considerations
All the analyzed medical charts included patients’ informed consent
for processing of their personal data for research and educational
purposes.
List of abbreviations
5-HTTLPR= Serotonin-transporter-linked polymorphic region
APTT= Activated partial thromboplastin time
APTT= activated partial thromboplastin time,
BMI= body mass index
DSM= Diagnostic and Statistical Manual of mental Disorders
ICD= International Classification of Diseases
INR= International normalized ratio
MDD= major depressive disorder
MI= myocardial infarction
PAP= plasmin-alpha2-antiplasmin complex
SERT= serotonin transporter
SSRI= Selective serotonin reuptake inhibitor
References:
1. Reikvam AG, Hustad S, Reikvam H, et al., The effects of selective serotonin reuptake inhibitors on platelet function in whole blood and platelet concnetrates. Platelets 2012;23(4):299-308.
2. Abdelmalik N, Ruhe HG, Barwari K, et al., Effect of the selective serotonin reuptake inhibitor paroxetine on platelet function is modified by a SLC6A4 serotonin transporter polymorphism. J Thromb Haemost 2008;6(12):2168-74.
3. Geiser F, Conrad R, Imbierowicz K, et al., Coagulation activation and fibrinolysis impairment are reduced in patients with anxiety and depression when medicated with serotoninergic antidepressants. Psychiatry Clin Neurosci 2011;65(5):518-25.
4. Shapiro PA, Lesperance F, Frasure-Smith N, et al., An open-label preliminary trial of sertraline for treatment of major depression after acute myocardial infarction (the SADHAT Trial). Sertraline Anti-Depressant Heart Attack Trial. Am Heart J 1999;137(6):1100-6.
5. Siddiqui R, Gawande S, Shende T, et al., SSRI-induced coagulopathy: is it really? Ther Adv Psychopharmacol 2011;1(6):169-
74.
6. Ford MA, Anderson ML, Rindone JP, Jaskar DW, Lack of effect of fluoxetine on the hypoprothrombinemic response of warfarin. J Clin Psychopharmacol 1997;17(2):110-2.
7. Teichert M, Visser LE, Uitterlinden AG et al. Selective serotonin re-uptake inhibiting antidepressants and the risk of overanticoagulation during acenocoumarol maintenance treatment. Br J Pharmacol 2011;72(5):798-805.
8. Limke KK, Shelton AR, Elliott ES, Fluvoxamine interaction with warfarin. Ann Pharmacother 2002;36(12):1890-2.
9. Yap KB, Low ST, Interaction of fluvoxamine with warfarin in an elderly woman. Singapore Med J 1999;40(7):480-2.
10. Apseloff G, Wilner KD, Gerber N, Tremaine LM, Effect of sertraline on protein binding of warfarin. Clin Pharmacokinet 1997;32(Suppl.1):37-42.
12
Article received on May 20, 2019 and accepted for publishing on June 21, 2019.
REVIEW ARTICLE
Improved methodology of using simulators develops better practical skills in laparoscopy of future residents
Cristian V. Toma1,2, Cristian S. Sima1,2, Daniel G. Radavoi1,2, Traian Constantin1,2, Daniel L. Bădescu1,2, Viorel Jinga1,2
Abstract: Background and aim: Minimally invasive surgery represents the actual tendency in many medical domains including urology. Gaining practical skills for these procedures becomes essential when preparing the future resident physicians in urology. The purpose of this study is to demonstrate that using medical simulation as an education tool improves the practical skills of the urology house officers in laparoscopy by using an accessible tool such as a box trainer.
Methods: The study includes the objective and subjective evaluation of the practical skills of 54 students with no experience in laparoscopy. Each participant was evaluated before doing the practical activity on the simulator both in a subjective manner by filling a self-evaluation form and also objectively by timing the duration of doing laparoscopic basic tasks, knot tying and realizing a continuous suture. The participants were divided in two groups (A-28 participants, B-26 participants). Each group executed the same procedures with the same instruments, but with a different teaching technique.
Results and conclusions: Medical education with the help of a laparoscopic box trainer simulator is a useful tool for improving practical abilities and the time of execution of general procedures.
Keywords: medical education, laparoscopy, box trainer simulator, students, methodology
INTRODUCTION
On a continuous way to become an overall gold standard
laparascopy and minimally invasive surgery in general shows
better results in terms of patient recovery, hospitalization
period, and fewer complications such as blood loss or side
effects due to less required analgesia when compared to
large open incisions [1]. Minimally invasive surgery also gives
the advantage of smaller wound infection rates [2], fewer
dehiscence rate and incisional hernia [1]. Key whole surgery
requires more time, energy and financial resources. For
example, the learning curve for laparoscopic radical
prostatectomy was slower than the previously reported
learning curves for open surgery [3]. All of these are due to
less tactile real feel, loss of depth understanding, fulcrum
effect and also due to manipulation: hand-eye coordination.
Young urologists, especially residents, should be better
prepared before performing their first interventions and this
can be done in a safe, repeatable environment with the help
of medical simulation.
Basic and essential skills such as camera manipulation,
moving objects, manipulating intracorporeal materials (i.e.
gauzes, tissue), knotting and suturing, tissue manipulation
can be trained using medical simulation. In laparoscopy
medical simulation can be trained with the help of basic
pelvic trainers, virtual simulators which can also help
improve procedural steps and live surgery on animal tissue
such as porcine models.
The most reproducible, accessible and economic way of 1 “Prof. Dr. Theodor Burghele” Clinical Hospital, Bucharest, Romania 2 “Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania
Corresponding author: Cristian V. Toma MD
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teaching laparoscopy to beginners is with pelvic trainers/box
trainers. Unlike open surgery where one can encounter
more learning possibilities, laparoscopic training for young
surgeons is a challenge in their formation.
Training with the help of medical simulation has the purpose
to transfer the acquired skills in the operating room [4]. In
order to establish a minimum standard of training the
European Society of Urology established a model called E-
BLUS European Basic Laparoscopic Urologic Skills.
This model has a set of validated exercises which are
applicable in urologic laparoscopic procedures. In addition to
repeating the video showed skills one can improve the
learning curves by identifying possible factors without taking
into account the native ability of the surgeon or his previous
surgical experience. [5] “And therefore I find that being a
surgeon is a vocational profession, such as the athletes and
airplane pilots” [6] thus meaning that the surgeon should
also exercise before passing to real life scenarios, exactly
how pilots train on advanced simulators in order to perfect
their skills.
OBJECTIVE
To assess the better methodology of learning basic urologic
laparoscopic skills by medical students using a box trainer.
METHODS
A study was realized with 54 medical students from all years
of study from the University of Medicine and Pharmacy
“Carol Davila” from Bucharest through from January 2017 to
November 2018. The participants signed an informed
consent and completed forms requiring basic demographic
data such as age, year of study, gender, will to pursuit
surgical careers and dominant hand.
The participants were divided in two groups. Group A had 28
students who were trained within 3 separate workshops (10,
9, 9) following one simple metho-dology; group B contained
26 participants who were divided in 3 separate workshops
(10, 8, 8) and followed a more explicit and didactic
technique.
All of the participants had to do the E-BLUS exercises. The
first time they realized each exercise they were timed and
after 15 minutes of practice they repeated the same
measurement. The selected time was 15 minutes in order to
have enough time, energy and concentration for the
students to perform the tasks.
The instructors were represented by either urologists or
general surgeons with laparoscopic experience. Pedagogical
skills of the instructors were a criteria for inclusion in the
study. All of the instructors who were part of the project had
to train other senior students or residents with the aim of
forming bench side instructors who would facilitate the
communication between participants and main instructor
and also give technical and logistic aid to the participants.
Tasks
The European training in Basic Laparoscopic Urological Skills
consists of an online theoretical course which is followed by
realizing 4 tasks in a specific amount of time. The tasks and
their demo version can be found on the uroweb.org website.
[7]
The tasks that were shown to GROUP A were similar to the
ones from the E-BLUS. Peg transfer and circle cutting were
identical. Needle guidance was observed in previous
workshops to discourage students due to its difficulty and
high energy consumption so we decided to take a thicker
thread/suture without a needle so it would be easier to
manipulate, but maintain the same rotation, piston like and
hand eye coordination requirement. The laparoscopic
suturing exercise was divided in two sub-tasks. The first one
was to make a laparoscopic intracorporeal surgical knot,
while the second one required for the volunteers to realize a
surgical knot, make 3 sutures and then close with a second
knot on a silicon model [8].
The methodology for group A was the following: instructor
delivered two 15 minutes presentations on laparoscopy in
general and laparoscopic instruments, after these all of the
procedures were shown one by one by the main instructor
at the demo pelvic trainer and immediately after the
participants repeated each procedure with measuring the
initial time and the after 15 minutes training timing.
Group B on the other hand repeated the same exercises,
received the same live demonstration and video support. In
addition to these, each of the exercise except circle cutting
had a 3 minute training session with different exercises. Peg
transfer exercise was preceded by lifting 6 pin board pins one
by one, passing them from one instrument to the other and
placing them in a plastic recipient. The thread passing
exercise was preceded by a 3 minutes exercise which
required passing of an articulated metal piece through a
fixed orifice.
The breakthrough of this project besides improving the
laparoscopic skills of all students was the significant
improvement in time for the knot and suturing part of the
workshop for Group B. The participants from Group B were
made to repeat the intra-corporeal knot with the
laparoscopic instruments under direct vision after the initial
timing was measured.
14
This was done by disconnecting the monitor and changing
the “abdominal wall” from the pelvic trainer with a
transparent plastic sheet. In this way the movements were
maintained restrained by the trocars, but the conversion
from 2D to 3D natural view was present.
As a result the students at a cognitive level saw the
procedure under 3D circumstances and when conversion to
conventional 2D laparoscopic conditions was made the
overall final improvement was significant as it will be shown
in the results section.
RESULTS
The average year of study was 3.58, the male-female ratio
was 1:1.4, and none of them had previous laparscopic
surgery experience. All of the presented times are median
scores over the same sector. All of the 28 scores of Peg
Transfer Before section were summed and then divided by
28. The same principle was applied to all sections. The Time
Difference column shows the performance in time before
the Group B and Group A.
Figure 1: Comparison between groups
As one can see in Table 1 there is no significant difference in
the before timing of the majority of exercises besides
knotting and suturing which was enhanced in Group B
probably due to the technique of showing the tasks under
natural view and than reproduce the gestures and steps
combining 3D cognitive perception with 2D laparoscopic
vision.
Table 1: Overall timing in both groups A and B
Task Group A Group B Time Diference Significant3
1. Peg Transfer Before 5:24 5:45 -0:21 No
Peg Transfer After 3:22 2:11 1:11 Yes
2. Thread Passing B1 5:31 5:32 -0:01 No
Thread Passing A2 3:07 2:07 1:00 Yes
3. Knot B 12:55 10:58 1:57 Yes
Knot A 9:14 4:47 4:27 Yes
4 Suture B 21:59 13:26 8:33 Yes
Suture A 16:03 8:49 7:14 Yes
5 Circle Cutting B 5:28 5:14 0:14 No
Circle Cutting A 3:26 3:24 0:02 No
1B – before 2A – after 3Significant – more than 59 seconds difference
There was no significant difference in the Circle cutting
group due to the fact that no extra exercise or technique was
used in the Group B in order to enhance the performance.
In group B there was significant difference even in the
“before” timing of knots and sutures probably due to the
enhanced abilities given by the two extra exercises.
The overall extension of the Group B training time given by
the three extra exercises of three minutes each was of nine
minutes in practical extra activity and 21 minutes required
to change the materials within the pelvic trainer.
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Figure 2: Comparison – linear interpretation
DISCUSSION
The timings could have been improved if the participants
would have had more ergonomic instruments. All of the
instruments had finger rings – Mayo Hegar laparoscopic
needle holder.
Due to technical possibilities the table on which we placed
the pelvic trainers had the same height which was
inappropriate for short or tall students. Step stools were
given to short students, but not offering them the best
conditions. Tall students had the same problem.
The three speakers who took part in this project had two
presences- one for group A and one for Group B. The sub-
instructors were the same along the entire project.
CONCLUSION
It is well known that medical simulation in laparoscopy has
its role in reducing the necessary time to acquire basic
urologic skills in a safe and repeatable environment without
the stress and pressure felt in operating room. This study
demonstrates that even simple methodology can enhance
the beginner’s basic laparoscopic skills. In addition, due to
experience, medical professional who teach these type of
procedures can accelerate the process with tips and tricks
which precede the proposed measuring tools. In this way the
time from transferring the skills from laboratory to the
operating room can be shortened and overall confidence of
the surgeon can be enhanced.
Disclaimer
Nothing to declare. No financial grants or other funding were used.
Aknowledgements: Medical Simulation Center “LifeSim”, Bucharest
for offering the box trainers and space.
References:
1. Henry MM, Thompson JN. Clinical Surgery. London: W B Saunders, 2001
2. Daniar K.Osmonov et al, Turk J Urol. 2018 Jul; 44(4): 303–310.
3. Andrew J Vickers et al, Lancet Oncol. 2009 May; 10(5): 475–480
4. Bonrath EM, Weber BK, Fritz M, Mees ST, Wolters HH, Senninger N, Rijcken E Surgery. 2012 Jul; 152(1):12-20.
5. Feldman LS, Cao J, Andalib A, Fraser S, Fried GM Surgery. 2009
Aug; 146(2):381-6.
6. Mischianu D - Being a surgeon - a terrible and fascinating job – RJMM, 2018 April, 25(4):3-4
7. http://uroweb.org/education/online-education/surgical-education/laparoscopy/
8. https://www.simulab.com/products/tissue-suture-pad-
package-0
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Article received on May 6, 2019 and accepted for publishing on June 23, 2019.
REVIEW ARTICLE
Current review of surgical management options for rotational alignment of the femoral and tibial component in total knee replacement
Bogdan Crețu1,2, Cătălin Cîrstoiu1,2, Ștefan Cristea1,3
Abstract: Rotational malalignment complication following TKA, is common but can be avoided with proper surgical technique. This paper reviews the literature regarding rotational alignment during TKA, femoral and tibial rotation, and highlights the techniques prior in obtaining proper rotational positioning, nevertheless correct positioning in all three planes is important.
Proper femoral component positioning in the axial plane is done using as landmarks the posterior condylar line (PCL), surgical transepicondylar axis (sTEA), anatomical transepicondylar axis and the trochlear anteroposterior (AP) axis. The paper describes the angular relationships between these landmarks and the distal femur. Axial tibial positioning is done when using intraarticular landmarks, the combination of more than one landmark could be a solution for solving this problem.
The consensus is that femoral component should be positioned according to TEA but the interobserver variability of this land mark is very high. The rotation of the tibial component remains an open subject, most studies suggesting a point between half of the distance of patellar ligament and 1/3 of the internal tuberosity as optimal landmark.
Keywords: total knee arthroplasty; femoral component rotation; tibial component rotation
INTRODUCTION
Total knee arthroplasty (TKA) is an intervention whose
efficacy in the treatment of gonarthrosis is well known and
documented [1]. The results of this intervention depend on
the correct positioning of the prosthetic components in all
three planes: frontal, sagittal, and axial [2]. The axial plane
within TKA is represented by the alignment of the prosthetic
components in the rotational plane. In 1979, Mochizuki and
Schurman, who have shown that a lateral force produces the
sprain of the patella when the tibial component is positioned
according to the posterior plateau, described the
importance of rotational positioning. They recommended
that the tibial component should be aligned with the tibial
tuberosity and the femoral component in a relative external
rotation to the tibia at the time of a complete extension [3].
Femoral component positioning errors in the axial plane lead
to complications in the femuropatellar joint, ligament
instability and changes in normal kinematics [4]. The
positioning of the tibial component from a rotational point
of view has not been as studied, but its importance is equally
large. The malposition of the tibial component is indirectly
responsible for the femuropatellar complications that are
often the cause of postoperative knee pain, reduced mobility
and early revision [5]. Although current instrumentation
methods have greatly reduced the malposition rate of
1 “Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania 2 Department of Orthopedics and Traumatology, University Emergency Hospital, Bucharest, Romania 3 Department of Orthopedics and Traumatology, Pantelimon Emergency Hospital, Bucharest, Romania
Corresponding author: Bogdan Cretu, MD
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components, the subject of rotation is not a closed one, and
there is no consensus for the perfect positioning.
In this paper, we will try to present a review of recent
literature on the correct rotational positioning of the
femoral and tibial component, to describe the different axes
guiding the rotational alignment, and to compare the known
techniques.
ROTATION OF FEMORAL COMPONENT
The correct positioning of the femoral component from a
rotational point of view is an important step for the success
of TKA. The positioning of the femoral component in axial
plane has repercussions on stability in flexion, knee
kinematics, flexion alignment and femuropatellar joint [6, 7].
Berger demonstrated the relationship between the internal
rotation of the femoral component and the patellar
maltracking [8]. He was the first to use the CT to evaluate the
rotation of prosthetic components. He showed that a low
internal rotation, between 1 and 4o would lead to patellar
maltracking and tilting, an average internal rotation,
between 5 and 8o would lead to subluxation and a severe
internal rotation of 7-17o, would lead to the sprain of the
patella. For the analysis of both femoral and tibial rotation,
Berger used the transepicondylar axis (TEA) and tibial
tuberosity as anatomical landmark.
The external rotation of the femoral component also has
negative repercussions on the TKA. Olcott et al. have shown
that with the increase of external rotation of the femoral
component, the medial flexion space increases, the result
being a flexion instability symptomatology [9]. Another
study led by Hanada et al. has shown that the excessive
external rotation of the femur leads to varus flexion, the
result being an excessive loading of the external
compartment [10].
The consequences of external femoral rotation are well
known; the best landmark for a good rotation is a topic yet
debated. Many landmarks and axes have been described at
the level of distal femur: posterior condylar line (PCL),
transepicondylar axis (TEA), surgical transepicondylar axis
(sTEA), anteroposterior axis (AP) or Whiteside line anterior
femoral axis [11, 12].
“Tension gap” technique
The purpose of this technique is that after creating the gaps,
the flexion space should be rectangular and equal to the
extension space [13]. The soft parts of the knee are first
balanced in complete extension by ligament rebalancing and
subsequently at 90o flexion, either manually or with a
laminar spreader. The aim is to obtain equal ligament
tension both internally and externally and, after creating the
posterior femoral cuts, the posterior femur should be
parallel to the tibial surface after proximal tibial resection so
that this space is rectangular. To support this theory, Laskin
compared two groups of patients, in one group, the size of
posterior femoral cuts was equal, and in the second group,
the resection plane of posterior condyles was externally
rotated to obtain a rectangular space. He noted that for this,
it is necessary that the posterior medial femoral cut is larger
than the lateral one, with a relative increase of this
difference in the valgus knees due to lateral femoral
condylar hypoplasia. The average external rotation for
flexion space rectangulation was 3.20 to the posterior
condylar line [14].
Correct valgus or varus extension positioning is a problem
solved by current instrumentation systems but varus or
valgus flexion alignment is often forgotten. This problem was
investigated in a cadaver study, in which they compared the
“tension gap” technique with the anteroposterior axis
(Whiteside’s Line). Using the “tension gap” technique, they
noted that they had good stability in extension and flexion,
but the knees had varus deviations at flexion with an average
of 8.2 , increasing pressure in the internal compartment.
This phenomenon is largely due to the lateral collateral
ligament, which in a normal knee is slightly laxer than the
medial, this allowing the tibia to be pushed into varus
(allowing the internal rotation of the femur against the tibia)
when using the tensioning methods of equalizing the
tensions between the two ligaments [15]. In the group in
which the antero-posterior axis was used, the results were
better in terms of stability and alignment.
Transepicondylar axis (TEA)
It is defined as a line crossing the two epicondyles, medial
and lateral. This approximates the flexion-extension axis of
the knee [16]. The positioning of the femoral component in
the axial plane according to this line leads to an optimal
patellar tracking, decreases the shearing forces at the
beginning of flexion, and decreases the use of polyethylene
insert. Internal or external rotations to this axis will result in
changes in the patellar tracking [17]. The defect of this axis
is that it cannot be located accurately intraoperatively.
Berger et al. examined the knees of 75 cadavers and came to
the following conclusions: surgical TEA is the axis between
the lateral epicondyle and the medial sulcus, a channel
below the medial epicondyle [18]. They concluded that the
medial sulcus was an easily identifiable anatomical landmark
and measured the difference between surgical TEA and the
posterior condylar line as being 3.5○ in males and 0.3○ in
females. After studying 32 cadavers, Yoshioka et al.
concluded that there is a “condylar twist angle” of 5○ in
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males and of 6○ in females [19]. Although TEA is an axis
difficult to highlight during surgery, especially in cases of
significant destructive changes or in revisions, it could be the
most accurate landmark for determining the rotation of the
femoral component.
Posterior condylar line (PCL)
Using the posterior condylar line as a landmark for
determining the femoral rotation is a well-known and
generally accepted technique. PCL is on average 3-5○ in
internal rotation than TEA [20]. Most of the TKA instruments
kits have additional pieces for external rotation attached to
the instrument that palpates the posterior condyles, which
try to position the two pins of the femoral cutting block
parallel to TEA. In examination, PCL is identified by
digitization and the desired external rotation is added to it.
Different studies highlighted that optimal patellar tracking
was obtained with external rotation of the femoral
component. Patients with the femoral component in
external rotation do not need a rebalance of the extensor
retinaculum and have better postoperative patellar tracking.
This classic technique of positioning the femoral component
in external rotation is easy to use but has the disadvantage
that posterior condyles have to be perfectly palpated. This is
not always possible due to the size differences of posterior
condyles especially in cases of genu valgus with lateral
femoral condylar hypoplasia in which there is a risk of
internal rotation of the femoral component.
Trochlear anteroposterior (AP) axis
Also called the Whiteside line, the trochlear anteroposterior
(AP) axis was originally described as a landmark in
unicompartmental arthroplasty [21]. It was later used as a
landmark for the positioning of the femoral component in
axial plane in valgus deviation knees. It is defined as a line
that joins the deepest point of femoral trochlea with the
center of the deep lateral femoral notch. The perpendicular
line on the AP axis is about 4○ of external rotation compared
to PCL. TEA has an average of 4.4○ of external rotation
compared with AP axis. The AP axis has the advantage of
being easy to use and it can be identified during basic TKA.
TIBIAL COMPONENT ROTATION
The tibial component rotation is at least as important as the
rotation of femoral component. The positioning of the tibial
component in axial plane is responsible for optimal patellar
tracking. An internal rotation will lead to a lateralization of
tibial tuberosity and an increase of Q angle that will
predispose to the subluxation of the patella [22]. The
optimal tibial component position is not known exactly but
we know that higher revision rates occur, and the clinical
results are weaker at the time of malposition of the tibial
component [23]. Many intra- and extra-articular landmarks
are known. Intra-articular landmarks are tibial tuberosity,
patellar ligament, and posterior tibial axis. There is also an
option of alignment with the femoral component implanted
according to TEA in extension [24]. Another option is to place
the tibial component so that we have maximum tibial
coverage [25]. The extra-articular landmarks are the
transmalleolar axis of the ankle and the metatarsal II axis.
The decision regarding what type of landmark to use for the
axial alignment of the tibia is a difficult one and is influenced
by other intraoperative factors. The external rotation of the
plateau increases when an external parapatellar approach is
used and an incomplete tibial plateau exposure resulting in
internal rotation of the plateau [26].
Finding the optimal rotation of the tibial plateau requires a
deep understanding of knee kinematics. In a normal knee,
the tibia makes an internal rotation motion at the time the
knee is in flexion and an external rotation motion at the end
of the extension. This mechanism of external rotation at the
end of the extension is called “screw home mechanism”, due
to the geometry of the joint surfaces combined with the
cruciate ligaments [27].
This physiological movement occurs between 0 and 15○ of
flexion. Often, this mechanism sometimes disappears, is low
or paradoxically appears after TKA [28]. To reduce
polyethylene use, we need to obtain a better axing of the
two components in axial plane after TKA. The aim is to have
a neutral rotation between the two components during the
entire flexion, the rotational gap leading to femorotibial
subluxation and early destruction of the polyethylene
insertion.
Extra-articular landmarks
The most known extra-articular anatomic landmarks for
rotation positioning of the tibial component are the
transmalleolar axis of the ankle and the metatarsal II axis.
Both axes have a significant variability in their knee
orientation in different individuals [29]. In conclusion, these
landmarks should not be the only ones used to determine
the rotation. Extra-articular deformities secondary to
trauma or arthrosis may result in alteration of these
landmarks relative to the knee [30].
Intra-articular landmarks
Anterior tibial tuberosity is the most commonly used
anatomical landmark for the proper determination of tibial
plateau rotation. It is a landmark easy to identify and is not
modified by gonarthrosis. This anatomical structure was split
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to increase the efficiency of its identification and its use. To
determine the rotation, the internal edge of the tuberosity
and 1/3 of the internal tuberosity are used [30].
In a study using the CT, the medial edge of the tuberosity was
used in a lot of patients and in the second lot of patients, 1/3
of the internal tuberosity was used for the positioning of the
tibial plateau in axial plane. The femoral component in all
patients was positioned according to TEA. In the lot of
patients in which 1/3 of the internal tuberosity was used as
landmark, the femorotibial gap was lower, 67.5% of the
patients between ±5○, 85% between ±10○ and 97.5%
between ±20○, compared to the lot of patients in which the
medial edge of tuberosity was used, 3.8% of the patients
between ±5○, 15% between ±10○ and 68.8% between ±20○.
In conclusion, the authors support the use of 1/3 of the
internal tuberosity as landmark for the positioning of the
tibial plateau [31].
Another study evaluated the relationship between TEA, the
patellar ligament, and the posterior tibial axis in 30 healthy
patients by MRI [32]. They found that the perpendicular line
on TEA intersects the middle of the patellar ligament, the
intersection being at about 41% of the width of the tendon
measured from its internal edge. In order to have a smaller
gap between the femur and the tibia, the anteroposterior
axis of the tibial component must intersect the patellar
ligament and the femoral component aligned with the TEA.
This technique will finally result in a lack of coverage of the
posteromedial tibia of about 5 mm with a variation between
2 and 10 mm. The patellar ligament is not modified by
gonarthrosis, but its width is variable depending on the
surgical approach. When the tibial plateau is positioned
depending on the posterior cortex, it will enlarge the tibia
coverage, but will also greatly raise the rate of the internal
rotation of the tibial plateau. The authors of the study
concluded that the optimal landmark is an immediate point
located medial to the patellar ligament. The normal
anteroposterior diameter of the tibial plateaus is different,
and this will lead to the highlighting of the posteromedial
bone at the time the tibial plateau is positioned correctly.
“Self-seeking” method
This method involves introducing trial components and
performing full flexion and complete extension. The trial
tibial plateau will be rotationally positioned according to the
femoral component. The center of the trial tibial component
is marked with the electrocautery and the final implantation
is made using this point as landmark. This technique depends
on the correct positioning of the femoral component, in
femoral malrotation, the tibial component will also be
affected. There is a risk that, when the femoral component
is positioned in internal rotation and the tibial plateau is
internally rotated, major problems of patellar tracking occur
together with an increased instability. In order to overcome
this problem and at the same time to use it, it is
recommended to use a mobile plateau that will rebalance
the tibiofemoral gap.
The mobile tibial plateau or “mobile-bearing” was built so
that the polyethylene insertion follows the femoral
component in rotation and the tibial component in flexion-
extension. “Mobile-bearing” TKA reduces the need for tibial
component placing in a perfect rotation and reduces the gap
between the tibia and the femur. The disadvantage is that a
second joint surface is created between the insertion and
the tibial plateau and the destruction of polyethylene can
occur at both interfaces.
CONCLUSIONS
TKA function and survival depend on an optimal rotation of
the femoral component but also of the tibial component.
The positioning of the femoral and tibial component is well
known in the sagittal and frontal plane, but it is not very clear
in the axial plane. There is a consensus that the femur should
be positioned according to TEA but the methods this would
be possible are not optimal. The combination of different
techniques and the use of many landmarks could be a
solution. The rotation of the tibial component remains an
open subject, most studies suggesting a point between half
of the distance of patellar ligament and 1/3 of the internal
tuberosity as optimal landmark.
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7. Churchill JL, Khlopas A, Sultan AA, Harwin SF, Mont MA. Gap-Balancing versus Measured Resection Technique in Total Knee Arthroplasty: A Comparison Study. J Knee Surg. 2018 Jan;31(1):13-16. doi: 10.1055/s-0037-1608820. Epub 2017 Nov 27.
8. Berger RA, Rubash HE, Seel MU, et al. Determining the rotational alignment of the femoral component in total knee arthroplasty using the epicondylar axis. Clin Orthop. 1993;286:40-7.
9. Olcott CW, Scott RD. Femoral component rotation during total knee arthroplasty. Clin Orthop Relat Res. 1999;367
10. Hanada H, Whiteside LA, Steiger J, et al. Bone landmarks are more reliable than tensioned gaps in TKA component alignment. Clin Orthop. 2007;462:137-42.
11. Chon JG, Sun DH, Jung JY, Kim TI, Jang SW. Rotational alignment of femoral component for minimal medial collateral ligament release in total knee arthroplasty. Knee Surg Relat Res. 2011 Sep;23(3):153-8. doi: 10.5792/ksrr.2011.23.3.153. Epub 2011 Sep 26.
12. Yoshii I1, Whiteside LA, White SE, Milliano MT. Influence of prosthetic joint line position on knee kinematics and patellar position. J Arthroplasty. 1991 Jun;6(2):169-77.
13. Hommel H1, Perka C2. Gap-balancing technique combined with patient-specific instrumentation in TKA. Arch Orthop Trauma Surg. 2015 Nov;135(11):1603-8. doi: 10.1007/s00402-015-2315-6. Epub 2015 Aug 28.
14. Laskin RS. Flexion space configuration in total knee arthroplasty. J Arthroplasty. 1995;10:657-60.
15. Whiteside LA, Arima J. The anteroposterior axis for femoral rotational alignment in valgus total knee arthroplasty. Clin Orthop Relat Res. 1995;321:168-72.
16. Franceschini V1, Nodzo SR1, Gonzalez Della Valle A1. Femoral Component Rotation in Total Knee Arthroplasty: A Comparison Between Transepicondylar Axis and Posterior Condylar Line Referencing. J Arthroplasty. 2016 Dec;31(12):2917-2921. doi: 10.1016/j.arth.2016.05.032. Epub 2016 May 27.
17. Victor J1. Rotational alignment of the distal femur: a literature review. Orthop Traumatol Surg Res. 2009 Sep;95(5):365-72. doi: 10.1016/j.otsr.2009.04.011. Epub 2009 Jul 9.
18. Berger RA, Crossett LS, Jacobs JJ, et al. Malrotation causing patellofemoral complications after total knee arthroplasty. Clin Orthop. 1998;356:144-53.
19. Yoshioka Y, Siu D, Cooke TD.The anatomy and functional axes of the femur. J Bone Joint Surg. 1987;69:873-80.
20. Park A, Duncan ST, Nunley RM, Keeney JA, Barrack RL, Nam D. Relationship of the posterior femoral axis of the "kinematically
aligned" total knee arthroplasty to the posterior condylar, transepicondylar, and anteroposterior femoral axes. Knee. 2014 Dec;21(6):1120-3. doi: 10.1016/j.knee.2014.07.025. Epub 2014 Jul 25.
21. Whiteside LA, Kasselt MR, Haynes DW. Varus-valgus and rotational stability in rotationally unconstrained total knee arthroplasty. Clin Orthop Relat Res. 1987.219: 147-57
22. Nedopil AJ, Howell SM, Hull ML. Does Malrotation of the Tibial and Femoral Components Compromise Function in Kinematically Aligned Total Knee Arthroplasty? Orthop Clin North Am. 2016 Jan;47(1):41-50. doi: 10.1016/j.ocl.2015.08.006.
23. Panni AS, Ascione F, Rossini M, Braile A, Corona K, Vasso M, Hirschmann MT. Tibial internal rotation negatively affects clinical outcomes in total knee arthroplasty: a systematic review. Knee Surg Sports Traumatol Arthrosc. 2018 Jun;26(6):1636-1644. doi: 10.1007/s00167-017-4823-0. Epub 2017 Dec 15.
24. Eckhoff DG, Piatt BE, Gnadinger CA, et al. Assessing rotational alignment in total knee arthroplasty. Clin Orthop. 1995;318:176.
25. Martin S, Saurez A, Ismaily S, Ashfaq K, Noble P, Incavo SJ. Maximizing tibial coverage is detrimental to proper rotational alignment. Clin Orthop Relat Res. 2014 Jan;472(1):121-5. doi: 10.1007/s11999-013-3047-y.
26. Passeron D, Gaudot F, Boisrenoult P, et al. Does lateral versus medial exposure influence total knee tibial compo nent final external rotation? A CT based study. Orthop Traumatol Surg Res. 2009;95:420-4.
27. Collins DJ1, Khatib YH2, Parker DA3, Jenkin DE4, Molnar RB5. Tibial rotation kinematics subsequent to knee arthroplasty. J Orthop. 2015 Jan 30;12(1):7-10. doi: 10.1016/j.jor.2015.01.012. eCollection 2015 Mar.
28. Stiehl JB, Dennis DA, Komistek RD, et al. In vivo deter- mination of condylar lift-off and screw-home in a mobile- bearing total knee arthroplasty. J Arthroplasty. 1999,14 293
29. Miyanishi K, Nagamine R, Murayama S, et al. Tibial tubercle malposition in patellar joint instability: A computed tomography study in full extension and at 30 degree flexion. Acta Orthop Scand. 2000;71:286-91
30. Akagi M, Mori S, Nishimura S, et al. Variability of extraarticular tibial rotation references for total knee arthroplasty. Clin Orthop Relat Res. 2005;436:172-6.
31. Lutzner et al. Rotational alignment of the tibial component in total knee arthroplasty is better at the medial third of tibial tuberosity than at the medial border. BMC Musculoskeletal Disorders. 2010. 11:57
32. Incavo SJ, Coughlin KM, Pappas C, et al Anatomic rotational relationships of the proximal tibia, distal femur and patella: implications for rotational alignment in total knee arthroplasty. J Arthroplasty. 2003;18:643-8.
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Article received on February 19, 2019 and accepted for publishing on March 23, 2019.
ORIGINAL ARTICLES
The risk of bioterrorist and biocrime attack in the contemporary world
Ioana A. Gal1, Teodora B. Eremia1, Mihail S. Tudosie1,2, Viorel Ordeanu1,3,4
Abstract: The biological attack is the artificial spread by various means of pathogens that can cause serious infectious and contagious diseases as well as the spread of germ toxins that can be used by an aggressor as a means of fighting in order to reduce the troops’ fighting force, by causing serious disease outbreaks or by killing people, animals and/or plants.
Biological agents are microorganisms and/or microbial, animal or plant toxins, used as specific ammunition for biological weapons or used by terrorists in "bio-chem" attacks.
The risks of bioterrorism and biocrime attack in the contemporary world are real, and the history of the 20th century and the beginning of the 21st century confirms this.
It is necessary for preventive measures to be implemented on the unlawful use of biological agents. Early medical and non-medical countermeasures must be prepared for the prophylaxis, treatment and cessation of the consequences of any biological attack.
Keywords: biological attack, bioterrorism, biocrime, medical protection
INTRODUCTION
The biological attack is the artificial spread by various means
of pathogens that can cause serious infectious and
contagious diseases as well as the spread of germ toxins that
can be used by an aggressor as a means of fighting in order
to reduce the troops’ fighting force, by causing serious
disease outbreaks or by killing people, animals and/or plants.
Biological agents are microorganisms and/or microbial,
animal or plant toxins, used as specific ammunition for
biological weapons or used by terrorists in "bio-chem"
attacks.
Terrorism, according to the League of Nations (1937), can be
defined as the totality of criminal acts directed against a
state or made or planned in order to create a state of terror
in the minds of certain individuals, a group of people or the
general public.
The objectives of terrorism can be grouped as follows:
a) Achieving political goals.
b) Attracting the attention of domestic and international
public opinion to the "noble goal" pursued.
c) Undermining the authority of political regimes in some
countries by creating a state of inner strain, insecurity and
uncertainty, economic and social chaos.
d) Forcing authorities to meet certain requests.
g) Revenge on some officials.
h) Achieving military goals: management disruption at a
strategic or operational level, diminishing or partially
destroying the opponent's military potential, the disruption
of the logistics system, paralyzing communications and
telecommunication systems.
1 The Military-Medical Institute, Bucharest, Romania 2 “Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania 3 Military Medical Research Center, Bucharest, Romania 4 “Titu Maiorescu” University, Bucharest, Romania
22
i) Religious fanaticism.
Bioterrorism consists in using or threatening to use the
weapon of mass destruction for claims, with the declared
intent of affecting the public health and/or the environment.
Currently, the following means are known for dispersing
biological agents:
- Using saboteurs;
- Using vectors of microorganisms such as insects, mites,
rodents or other infected animals;
- Incorporation of biological agents into explosive ammuni-
tion;
- Aerosolization – through aerosols released from the
ground, air or sea – is considered the most effective means
of contaminating large areas of territory within the shortest
feasible time interval.
With regard to the production of biological weapons, both
ordinary and resistant biological agents can be used, the
latter being preferred, because they cause a form of the
disease that can not be treated with the usual drugs, causing
a disease outbreak of greater magnitude and severity.
In general, biological attacks are masked by natural
epidemics, epizooties and epiphytosis, the latter two being
generally considered to be economic attacks, with the aim of
decreasing trade, implicitly, causing the decline of the
standard of living in the affected area.
Biological attacks can also be manifested in the form of
zooanthroponoses, affecting both animals and humans alike.
[1, 2].
BRIEF HISTORY
"Read the history and, thus, discover what will be" Nicolae
Iorga rightly said. The first "chemical weapons" - "toxic
smoke" were used around 424 BC in the Peloponnesian War.
The first users of the "biological weapon" (around 400 BC)
can be considered the Scythians, who used arrows soaked in
decomposing bodies or mixed with manure. The Spartans
used to cast sieves of sulfur-moistened wood on sieged
fortresses. Greek, Persian, and Roman literatures describe
how dead animals were used for fountain-contaminate.
The Mongols, in the siege of the Kaffa fortress in Crimea,
during the war waged between 1346 and 1347, used the
corpses of those killed by the plague in order to infect or
create a breach among the fortress defenders.
In the fifteenth century, the Spanish infested the French
wine with blood from those infected with the pests. Also, at
that time, Pizzaro distributed to the Americans in South
America garments contaminated with smallpox. In the
sixteenth century, the same virus was used by the English to
impregnate the blankets distributed to the ameridian tribes
that helped the French. In the war against Sweden in 1710,
the Russian troops used the same method as the Tartar army
did 400 years prior – namely, the use of the corpses of those
killed by the plague.
Table 1. Cases of illicit activity with biological agents around the world, confirmed by the judicial system, 20th century (W.S. Carus)
No Objectives Category TOTAL
cases Comments
Terrorist Criminal Others/not specified
1 Killing 4 17 0 21
2 Terror 6 9 22 37
3 Extortion 0 13 3 16
4 Losses 0 5 0 5
5 Anti-animal or cultures 1 2 0 3
6 Mass murder 4 0 0 4
7 Revenge 0 3 0 3
8 Disability 2 0 0 2
9 Political 1 0 0 1 The fewest
10 Unknown 9 7 72 88 The most
TOTAL 27 56 97 180
Comments The
fewest The most
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Table 2. The objectives of using biological agents in the 20th century (W. S. Carus) [α]
No Activity Category TOTAL
cases Comments
Terrorist Criminal Others/not specified
1 Acquisition and use 5 16 0 21
2 Acquisition (possession) 3 7 2 12
3 Interest (attempt) 6 4 0 10 The fewest
4 Threat or false attack 13 29 95 137 The most
TOTAL 27 56 97 180
Comments The
fewest The most
During the Vietnam War, Americans used defoliant,
desiccant and sterilizing herbicides. These substances did
not fall under the Geneva Protocol of 1925 nor in the
Convention on the Prohibition of Chemical Weapons. In the
1970s, ricin was used to assassinate Bulgarian dissidents
Gheorghe Markov and Vladimir Kostov.
In 1976, the mayors of several US cities were the recipients
of letters that were delivered in envelopes on which had
been used an adhesive impregnated with lethal germs.
In 1979, among people working in a military microbiology
unit, was recorded an epidemic of lung anthrax, resulting in
over 60 deaths.
In 1984, in the US, members of the Bhagwan Shree Rajneesh
sect have contaminated the food in Oregon restaurants with
Salmonella Tiphi, causing 750 cases of major disease
outbreaks.
In 1988, Iraq was spreading toxic and biological substances
in Halabja, causing victims among the civilian population,
predominantly children and women. Also in 1995, Iraq
admitted to having in its posession Bacillus anthracis,
botulinum toxin and aflatoxins, declaring to be ready to use
them. All this demonstrates that, although the Convention
on the Prohibition of Chemical Weapons was signed in 1972,
the biological weapons research continued.
Since the end of 1992, there have been many more complex
epidemics in the US, Milwaukee area, with wide-ranging
effects: 400,000 cases of crypto-sporidium outbreaks from
water consumption; in the spring of 1993, a respiratory
epidemic with unidentified causes; during the fall of 1994,
250,000 cases of salmonella food poisoning.
On October 5th, 2001, in the US, Florida area, after having
inhaled the anthrax bacillus, a tabloid’s editor passed away.
On October 20th, 2001, three letters containing anthrax
spores were delivered to Washington DC, USA, having been
received by Tom Daschle, a member of the Senate, and by
Tom Brokaw from NBC News, as well as by the newspaper
"The New York Post ". On November 2nd, 2001, a letter
containing anthrax spores was found in Karachi, Pakistan,
which was addressed to the newspaper "Daily Jang". In
Santiago, a similar postal mailing resulted in disease
outbreaks of thirteen people.
Figure 1. Frequency of the illicit use of biological agents in the
20th century, on decades (W. S. Carus) [α]
After September 11, 2001, the danger of massive terrorist
attacks on the population of any part of the world is no
longer just a working hypothesis. Chemical, biological or
nuclear terrorism is, at present, one of the most serious
threats to all states. Given the trend of interethnic and
religious violence, as well as the number of cases of human
rights violations in certain "high-risk" areas around the
globe, analysts have warned against accentuating the risk of
using these types of weapons in terrorist actions, underlining
the imperative nature of urgently establishing non-
proliferation measures.
Table 3. Type of biological agent used (W.S. Carus) [α]
1 Living agents 136 cases
2 Toxins 26 cases
3 Unknown 6 cases
TOTAL 168 cases
24
COUNTERMEASURES
Combating bioterrorist attacks involves, first of all, the
intervention of the secret services, the police and the judicial
system. Also, the intervention of the National Health System,
the National Defense System, local communities and non-
governmental organizations is crucial in the fight against
these attacks. These non-medical contermeasures have an
active, prophylactic role, preparing the population in the
event of an attack. [3, 4, 5]
Table 4. Dissemination technique (W. S. Carus) [α]
No Dissemination Category TOTAL
cases Comments
Terrorist Criminal Others/not specified
1 Aerosolization 2 0 0 2 The fewest
2 Injection/topic 6 10 0 16
3 Food 1 20 1 22
4 Water 4 0 2 6
5 Natural vectors 0 1 1 2 The fewest
6 Not specified 10 13 79 102 The most
7 Unknown 5 10 2 17
TOTAL 28 54 85 167
Comments The
fewest The most
The responsibility for coordinating actions in these situations
lies with the government of the country holding the EU
Presidency, with the government of the country under
attack and/or with the European Center for Infectious
Disease Control.
The specific capabilities of the Medical Department of the
Ministry of Defense are important for the medical protection
against weapons of mass destruction and, in particular, for
the fight against biological attacks. The Center for Military
Medical Scientific Research has a Laboratory of Anti-
infective Medical Protection and Epidemiological
Emergencies, which functions as a specialized medical
protection unit against biological weapons. It conducts
military medical scientific research to protect troops and the
civilian population against biological weapons and/or toxins,
for biological warfare, bioterrorist attacks, or biological
accidents.
Table 5. The mortality rate in the attack with biological agents
(W.S. Carus) [α]
Purpose Cases Deaths
1 Bioterrorism 751 0
2 Biocrime 130 10
TOTAL 881 10
Source: Carus W. S. „Bioterrorism and Biocrimes. The illicit use of biological agents since 1990”, Center for Counterproliferation Research, National
Defense University, Washington DC, 2001. [6]
If we make a retrospective of the 20th century, the most
warrior of all, it is noticed that the practical use of
weapons/biological agents was a reality. [6]
It is noted that in the last decade of the 20th century there
were more cases than in the rest of the century.
OBSERVATION
An important component in the fight against biological
attacks is represented by medical espionage, a constantly
updated data base of new agents and existing diseases, thus,
becoming the key to finding the most effective treatment.
With regard to the measures required for the imminence of
a biological attack, individual protection means are used
such as the gas mask - which is not 100% effective, but it
decreases the amount of inhaled substance, having a
protective role, because for most substances in order for
harmfull effects to hapen it is necessary for large quantities
to be inhaled.
Chemotherapics present much wider benefits in regards to
the protection against biological weapons, acting switftly,
having a broad spectrum and being easily administered in
large communities.
Also, a very impressive step after a biological attack is the
decontamination by appropriate physical and chemical
means for the equipment, rooms, clothes, water sources,
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25
soil, etc. [7, 8, 9, 10]
CONCLUSIONS
The risks of bioterrorism and biocrime attacks in the
contemporary world are real, and the history of the 20th
century and the beginning of the 21st century confirms this.
It is necessary to implement preventive measures on the
unlawful use of biological agents. Early medical and non-
medical countermeasures must be prepared for the
prophylaxis, treatment and cessation of the consequences of
any biological attack.
References:
1. Ordeanu V., Andrieș A., Hîncu L., Microbiologie și protecție medicală contra armelor biologice, Editura Universitară „Carol Davila” București, 2008.
2. Păun, Ludovic, Bioterorismul şi armele biologice, Editura Amaltea, 2003;
3. *** S.R.I., Centrul de informare pentru Cultura de Securitate, Centrul de Cooperare Operativă Antiterorista, Inamicul invizibil. Bioterorismul și armele biologice în lume, www.sri.ro
4. Chiş, Ioan, Popa, Cristina, Terorismul contemporan –fenomen şi infracţiune, Editura A.N.I, Bucureşti, 2007
5. Tun-Comşa, Cristian, Consideraţii privind terorismul contemporan, www.actrus.ro
6. Carus W. S. „Bioterorism and Biocrimes. The illicit use of biological agents since 1990”, Center for Conterproliferation Research, National Defense University, Washington DC, 2001.
7. Ioana-Alexandra GAL, Teodora Bianca EREMIA, Mihail Silviu
TUDOSIE, Colonel (r.) Viorel ORDEANU „Riscul de atatc bioterorist și de biocrimă în lumea contemporană”, comunicare Conferința anuală SUUMC București, sept. 2018
8. Ionescu LE, Ordeanu V, Dogaru M, Necsulescu M, Popescu DM, Bicheru SM, Dumitrescu GV. „Research for the development of logistics planning information support in health protection against biological agents”, Romaniam Journal of Military Medicine, vol. 121, no. 1/2018, p. 36-39
9. Ordeanu V, Necsulescu M, Popescu DM, Ionescu LE, Bicheru SM, Dumitrescu GV., Corlan G. „The concept of operationalization of an integrated platform for scientific research and expertise of war end bioterrorism biological agents” Romaniam Journal of Military Medicine, vol. 120, no. 2/2018, p.9-15
10. Popescu DM, Necsulescu M, Popescu DM, Ionescu LE, Bicheru SM, Dumitrescu GV., Ordeanu V. „Capabilities for identification and confirmation of baterial biological agents” Romaniam Journal of Military Medicine, vol. 119, no. 3/2016, p. 5-9
26
Article received on December 4, 2018 and accepted for publishing on March 30, 2019.
ORIGINAL ARTICLES
The concept of biological warfare and real biological attacks
Teodora B. Eremia1, Ioana A. Gal1, Iulia M. Staicu1, Mihail S. Tudosie1,2, Viorel Ordeanu1,3,4
Abstract: In the current military-political context, with the Cold War having ended, we find ourselves in full anti-terror war, in which Romania is a direct participant, as a member of N.A.T.O. and the E.U., and the issue of biological warfare and bioterrorism is again highly topical but bearing other valences.
There is information that there are still laboratories and plants specializing in the research and manufacture of biological weapons. Most of the results of such research are not intended to be published; however, a number of research guidelines that testify to the trends in the improvement of biological weapons and their means of use can be deduced from the data published by researchers from several research institutes.
We believe that the threats posed by bioterrorism are real and that it is mandatory to be prepared at any time to prevent, combat and liquidate the consequences of "bio-chem" attacks, respectively the management of the consequences.
Keywords: biological attack, biological warfare, biological agents, international legislation, medical protection
INTRODUCTION
In the current military-political context, with the Cold War
having ended (1947-1990), we find ourselves in full anti-
terror war (since 2001), in which Romania is a direct
participant, as a member of NATO and the EU, and the issue
of biological warfare and bioterrorism is again highly topical
but bearing other valences.
DEFINITIONS
War is a short or lasting conflict (whether military or not,
declared or not), between two or more groups, social
categories or countries, aiming to achieve financial, ethnic,
territorial, economic and political interests.
The biological warfare is the artificial spread by various
means of pathogens that can cause serious infectious and
contagious diseases as well as the spread of germ toxins that
can be used by an aggressor as a means of fighting in order
to reduce the troops’ fighting force, by causing serious
disease outbreaks or by killing people, animals and/or plants.
Weapons of mass destruction (WMD) are those weapons,
which, used by the aggressor, cause extensive material
damage (destruction of buildings, constructions, machinery,
installations, means of transport, etc.) as well as a large
number of victims among employees and unprotected
animals.
Chemical, biological, radiological and nuclear defence (CBRN
defence) represents the protection measures taken during
times of war or terrorist attacks, in the event of a chemical,
biological or nuclear attack.
The biological weapon is a system of unconventional
weapons of mass destruction, whose ammunition carries
biological agents and contaminates the enemy in order to
cause disease outbreaks for the latter.
Biological agents are microorganisms and/or microbial,
1 The Military-Medical Institute, Bucharest, Romania 2 “Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania 3 Military Medical Research Center, Bucharest, Romania 4 “Titu Maiorescu” University, Bucharest, Romania
Vol. CXXII • No. 2/2019 • August • Romanian Journal of Military Medicine
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animal or plant toxins, used as specific ammunition for
biological weapons or used by terrorists in "bio-chem"
attacks.
Total war is a large-scale conflict in which policy makers
mobilize all available resources to ensure the destruction of
the rivals' ability to defend itself. During times of total war,
there are no actual non-combatants, meaning that all people
in a particular country - civilians and military alike – are
considered targets.
The hybrid war represents undeclared wars by those
participating states, where the military component is not
explicitly assumed and is by no means singular (they are
executed in concert as part of a flexible strategy with long-
term goals).
THE BIOLOGICAL ATTACK
Under the conditions of modern warfare, the effects of using
the biological weapon can be amplified by successive or
concurrent use with other WMDs. In a concrete battlefield,
the biological attack can occur with:
a) The enemy on the offensive – can use the biological
weapon to weaken the opponent's defence power. The most
likely objectives to be attacked with biological agents would
be:
1. Concentration of troops, resistance points
2. Reserve and support units
3. Air and sea troops found at bridge ends, traffic routes
clogs, operational reserves, etc.
In the tactical and operative space, pathogens of diseases of
short and virulent incubation, but non-transmissible from
human to human, will be used. Infected animals or insects
will not be used, as they would be dangerous for own troops.
In the strategic space, the aggressor will spread biological
agents that cause many types of diseases to disrupt the
battlefield, cause panic and aggravate material insurance.
b) The enemy on defence – could use the biological weapon
against opposing troop concentrations to reduce their force
of attack. Can be attacked with biological agents, the units in
the offensive, those in the second line or the back-ups, the
foreign military bases, etc.
In the operative space, infected insects and animals may also
be used to target troop concentrations; the passes, roads,
and crossing points may be contaminated to hinder the
pursuit.
Living organisms are the sole targets of these attacks, thus
buildings (for e.g.) being left intact, these being able to be
decontaminated and further used. The biological agent is
massively released into the area by the enemy and can
contaminate a large number of humans and/or animals
(anthroposoonosis) turning them into secondary sources of
infection by releasing in their turn pathogens in the external
environment. Except for those destined exclusively for
humans and for those common to both humans and animals,
there are also those biological agents destined exclusively
for the destruction of domestic animals and cultivated
plants.
THE PROVISIONS OF INTERNATIONAL LAW
From the point of view of International Law, biological
weapons are expressely prohibited because they fall under
the mass destruction weapons category, and their effect
cannot be limited in time and space, with medium-term
effects not always predictable. Moreover, the military use of
biological weapons is currently considered to be tactically
and operationally inefficient, being tactically difficult and
risky from a medical point of view, because an outbreak once
released can get out of hand.
Exceptions on using WMD
An important issue in controlling the Convention’s
implementation is the existence of certain exceptions
because the Convention cannot completely ban the use of
living agents and their toxins. So far, no convention banning
the use of a certain type of weapon against the enemy has
explicitly prohibited its use on its own population.
First of all, biological agents and some toxins can be used in
vaccine manufacturing, for diagnostic and treatment
purposes. For example, biological agents may be used in the
treatment of inflammatory bowel diseases such as Crohn's
disease inflammatory form with moderate or severe activity
that have not responded to conventional immune-
suppressive therapy or where immunosuppressant therapy
is contraindicated. They may also be used in patients with
moderate/severe RCUH who have not responded to
corticosteroid and immunosuppressive therapy or severe/
fulminant colitis. These patients are required to undergo
treatment with drugs such as Infliximab or Adalimumab
containing a chimeric anti-TNFα agent consisting of IgG1
monoclonal antibodies, 25% murine and 75% human,
respectively a fully humanized anti-TNFα agent, IgG1 type.
At the same time, the emergence of vaccines has greatly
revolutionized medical science since they carry an important
prophylactic role.
The vaccine is a biological product containing suspensions
(antigens) of attenuated, inactivated (killed) viruses or living
bacteria, or fractions thereof, which are administered in
28
order to induce a specific immune response. Depending on
the type of vaccine, fragments of pathogen agents were used
differently:
1. Viral vaccines – corpuscular vaccines with living
attenuated viruses (oral polio vaccine, rotavirus vaccine,
measles, rubella, varicella, amaryllis) or inactivated viruses
(inactivated polio vaccine, rabies, Hep A) and antigenic
fragments or viral subunits (Hep B, influenza vaccine)
2. Bacterial-corpuscular vaccines with living attenua-ted
germs (BCG) or killed (germs), (cholera vaccine, pertussis),
polysaccharide subunits (meningococcal, pneumococcal,
Hib, typhoid vaccine) or purified (pertussis acelular)
3. Anatoxin – diphtheria, tetanus
Thus, the BTWC allows all signatory countries to possess and
use reasonably small (grams) quantities of BWA for
defensive scientific research to obtain new means of
diagnosis, prophylaxis and treatment. But a real problem is
that these living biological agents can be multiplied on
demand and in any quantity or can synthesize toxins as
specific ammunition for biological weapons.
Secondly, one of the BTWC articles states that in case of
force majeure, when a state itself is threatened, it may notify
the UN three months before resuming the production of
biological weapons to deter the enemy. This also explains
why Israel, "an island in a sea of hostile Arabs", has not
signed and ratified the convention.
And Romania, which joined since 1972, ratified it only in
1979, in order to have an extra advantage in the face of a
possible assault of the USSR in the context after 1968. It
should be underlined that in fact Romania has not
researched, manufactured, stored, and has never used
biological or toxin weapons, nor did it have such an
intention, but it was indeed, the target of covert biological
attacks in the 20th century and, we must continue to take
preventive measures.
In this complex situation, effective legal measures for the
application of the BTWC need to be implemented
worldwide, but concrete actions are difficult to apply in
practice. The UN is in a position, as an international forum,
to impose and control compliance with the Convention,
being helped by the Security Council, the World Health
Organization as a specialized body.
STANAG are NATO standards for different areas that set
technical or operational standards in certain situations,
including in the field of biological warfare, and which need
to be adapted and implemented by Allied countries for
interoperability.
PREVENTION OF BIOTERRORISM ATTACKS
Preventing bioterrorist attacks is mainly a political and social
problem, which is primarily achieved through the
intervention of the secret services, police and the justice
system. Combating bioterrorist attacks also involves the
intervention of the National Health System, the National
Defence System, etc. The specific capacities of the Medical
Department of the Ministry of Defence are important for the
medical protection against the weapons of mass destruction
and especially for fighting against biological attacks,
permanently having the forces and means necessary for the
medical protection against the C.B.R.N agents.
The Center for Military Medicine Scientific Research
(CCSMM) has a Laboratory of Anti-infective Medical
Protection and Epidemiological Emergencies, which
functions as a specialized medical protection unit against
biological weapons. It conducts military medical scientific
research to protect troops and the civilian population
against biological weapons and/or toxins, for biological
warfare events, bioterrorist attacks, or biological accidents
targeting primarily: bacteria, viruses, fungi, etc. and their
toxins, to establish medical protection procedures, through
cooperation between different medical specialties:
microbiology, epidemiology, etc.
A first stage subsequent to the occurrence of a biological
attack is the identification of the causal agent, being
performed solely in a microbiology laboratory, starting from
correctly harvested samples (from the air, soil, water,
pathological products from the sick, etc.). The identification
operation must be quick and specific.
In the event of an immediate biological attack, the problem
at hand is the immediate decontamination by appropriate
physical and chemical means of the staff’s equipment, of the
rooms, the water sources and the food, etc. The appropriate
anti-epidemic measures to limit the spread of the infection
are, along with the above, another important stage in the
post-attack protocol, in which we will: isolate the sick and
the suspects, take care of individual and collective hygiene,
qarantine the D.D.D. actions and so on. If the agent has been
identified, we can perform emergency immunoprophylaxis
by using vaccines, by administering prophylactic or
therapeutic antibiotics, etc.
The protection against biological attacks depends on the
moment when the attack is detected, thus, when the media
shall signal the imminence of an attack, the possibility to
benefit from individual protection (ex-gas mask) and
collective protective means (shelters) should be available.
The biological means of protection and the emergency
prophylaxis with appropriate substances (serums, vaccines,
Vol. CXXII • No. 2/2019 • August • Romanian Journal of Military Medicine
29
etc.) can be of good efficacy. Immunostimulators and
chemo-therapeutic agents (wide-spectrum antimicrobials)
can also be associated with these.
THE BIOLOGICAL WARFARE – A HISTORICAL REVIEW
There are very few data from the Prehistory and Antiquity
that testify to the use of biological weapons during warfare.
However, the latest research attests to the fact that the
Hittites were the pioneers of bioterrorism. The Hittite people
lived on a territory that today belongs mostly to Turkey.
Three thousand years ago, they used infected sheep aiming
at conquering enemy people. According to the study
performed by the Italian microbiologist Siro Trevisanato, the
bacterium considered the first weapon of mass destruction
in history was Francisella Tularensis, responsible for
tularemia, an infectious and contagious rodent disease,
caused by a bacterium and transmitted to domestic animals
and humans, manifesting itself by fever, chills, vomiting, etc.
The disease still exists nowadays and, if not treated properly,
can lead to death. Studying ancient papers, researchers have
proven that tularemia first appeared in a Phoenician city
(located on the border between Lebanon and Syria today) in
the Middle East in the 14th century BC. The Hittites
plundered this city in 1325, bringing with them infected
animals, which may have spread the disease – also referred
to as the "Hittite Plague" - throughout its territory, as
explained by the researcher. Trevisanato points out that
there are several papers attesting the epidemic. At the time
of tularemia’s utter virulence, the Hittites came to the
attention of a neighboring population of the city of Arzawa
(Western Anatolia), who took advantage of their weakness
to invade their territory.
During the Middle Age as a Mongol saw his comrades die of
plague in the three years of the siege of Caffa's Black Sea city,
founded by the Genovese, he had the brilliant idea of
throwing corpses over the city walls. The Genoese left the
city, but the plague spread across Europe.
In the Modern Age – the First World War brought a more
sophisticated biological warfare, with the development of
microbiology, many pathogens causing diseases could be
identified that could then be cultivated in the laboratory.
There are suspicions about the use of plague against Russian
troops at St. Petersburg. Petersburg in 1915, about horses
being infected in US ports for British and French armies.
In the Contemporary Age – extraordinary intelligence has
been invested in the development and modernization of all
categories of weapons. Each country classified biological
programs at the highest level of secrecy; there is little
evidence today about the details of the programs being
carried out, with only little evidence on the existence of such
programs in the current media. Specific anti-human, anti-
animal and anti-plant programs have been developed,
agents have been standardized for use as weapons, and
insects have been studied for use as natural dispersion
vectors.
PERSPECTIVES
The range of pathogens used as biological weapons is very
wide, which gives rise to particular difficulties in the
elaboration of the protection and treatment measures.
Types of agents:
1. Bacteria: anthrax, plague, cholera etc;
2. Viruses: yellow fever, tick-borne encephalitis (TBE),
smallpox, etc;
3. Rickettsia: Q fever, exanthema of typhus etc;
4. Pathogenic fungi: coccidioidoreo etiological agents, etc;
5. Toxins: bacterial (Botulinum, staphylococcal, etc.), fungal,
of animals or plants (ricinotoxin).
These are only the pathogens found in nature. But new
genetic techniques now allow us to obtain germs with new
qualities, not naturally occurring (modified or hybridized)
and which can be considered more dangerous by their
pathogenic effect and increased resistance in the external
environment.
Some agents have a lethal effect, while others have an
incapacitating effect, leaving man out for a period of time
ranging from a few hours to a few weeks.
They can be joined by immunosuppressive substances,
which disrupt the mechanisms of the body's anti-infectious
resistance, exposing it to current infections or to those
deliberately disseminated.
In the case of a biological attack, it should be stressed that
the possibility of using two or more biological agents
simultaneously, whose effects combine or potentiate, or can
be used with other weapons of mass destruction, is
estimated.
We can also mention the existence of biological agents
destined exclusively for destroying domestic animals and
cultivated plants (e.g. avian influenza, barberry rust for
plants) that can lead to large losses or can be used to destroy
the economy of a competing country etc.
CONCLUSIONS
There is information that there are still laboratories and
plants specializing in the research and manufacture of
biological weapons. Most of the results of such research are
not intended to be published; however, a number of
30
research guidelines that testify to the trends in the
improvement of biological weapons and their means of use
can be deduced from the data published by researchers from
several research institutes (e.g. the study of some of the
most dangerous communicable diseases in humans and
animals that currently have a very narrow spreading area).
Another evidence of concern in the field of biological
weapons is that the military personnel of some states are
regularly exposed to prophylactic vaccines against some
infectious diseases that are not circulating in the respective
country.
We believe that the threats posed by bioterrorism are real
and that it is mandatory to be prepared at any time to
prevent, combat and liquidate the consequences of "bio-
chem" attacks, respectively the management of the
consequences.
References:
1. Mihail-Silviu Tudosie, Teodora Bianca Eremia, Ioana Alexandra Gal, Iulia Madalina Staicu, Viorel Ordeanu - Conceptul de razboi biologic si atacurile biologice reale, Comunicare Conferinţa Anuală a Spitalului Universitar de Urgenţă Militar Central “Dr. Carol Davila” Bucuresti 10-13 octombrie 2018
2. Ordeanu V. et all. Microbiologie si protectie medicala contra armelor biologice, Editura Universitara Carol Davila, Bucuresti, 2008
3. https://en.wikipedia.org/wiki/CBRN_defense
4. https://ro.wikipedia.org/wiki/R%C4%83zboi_biologic
5. http://www.ccpb.ro/despre-bioterorism/scurt-istoric-al-armei-si-razboiului-biologic
6. „Convenţia privind interzicerea perfecţionării, producţiei şi stocării armelor bacteriologice (biologice) şi cu toxine şi la distrugerea lor (BTWC)” http://www.ancex.ro/? pag=69
7. Convenţia pentru Arme Biologice, http://www.ccpb.ro/ despre-bioterorism/conventia-pentru-arme-biologice
Vol. CXXII • No. 2/2019 • August • Romanian Journal of Military Medicine
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Article received on April 15, 2019 and accepted for publishing on June 3, 2019.
ORIGINAL ARTICLES
Morphological characteristics of the celiac-mesenteric trunk
P. Bordei1, R. Baz1, V. Rusali1, Cristian R. Jecan2,3, V. Ardeleanu1,4,5,6
Abstract: The present paper describes the morphological characteristics of 12 celiac-mesenteric trunk cases highlighted by angiography-computed tomography (CT), characteristics met only in male cases (1.82% of the cases). In relation to the vertebral column, the origin of the trunk was found in the the upper half of the L1 vertebra – intervertebral disk between L1 and L2 vertebrae. At the level of its origin from the aorta, the celiac-mesenteric trunk had an external diameter with values ranging from 8.7-13.4 mm, the aortic ostium of the celiac-mesenteric had a vertical diameter ranging from 8.8 to 13.1mm, the horizontal diameter values ranging from 8.8 to 11.2mm. At the level of its origin, the celiac-mesenteric trunk and the aortic wall had an angle with values ranging from 30.0o to 90.2o. The length of the celiac-mesenteric trunk had values ranging from 21.8 to 42.5 mm, most frequently met values were ranging from 30.7 to 33.5mm. At the level of its bifurcation, the celiac-mesenteric trunk had an angle with values ranging from 82.2 to 120,7, most frequently met values were over 90o. The celiac trunk resulted from the celiac-mesenteric bifurcation had an exterior diameter of 6.2 – 10.2 mm, values that in relation to exterior diameter the celiac-mesenteric originated, it represented 65.57 – 92.47% of its external diameter. The celiac trunk up to the end of its ramification had a length with values ranging from 6.3 to 16.8 mm. In all cases being a hepatosplenic trunk, the left gastric aorta originated in the abdominal aorta in 10 cases (83,3% of the cases) and in the other 2 cases, the left gastric aorta originated in one case under the end bifurcation of the celiac trunk whereas the other case in the celiac-mesenteric trunk, before its end bifurcation. The superior mesenteric artery resulting from the ramification of the celiac-mesenteric trunk had an external diameter with values ranging from 4.4 to 8.5 mm that represented 44.44 – 85.06% of the external diameter of the celiac-mesenteric trunk.
Keywords: celiac-mesenteric trunk – morphological characteristics
INTRODUCTION
The celiac trunk and the superior mesenteric aorta are
collateral branches of the abdominal aorta that are
originating independently from its trunk, assuring the
vascularization of the biggest part of the digestive tube and
its annexed glands as well as the vascularization of the
spleen. There have been cases where both arteries
originated from the aorta through a common trunk, the
celiac-mesenteric trunk, with frequencies of [1] and 3% [2, 3]
– most authors pointing a percentage between 1.0 and 2.5%
of the cases. According to [4], during the embryonal
development, out of the 4 roots of the omphalomesenteric
artery, roots 2 and 3 will disappear and the persistent root
will unite by longitudinal anastomosis resulting into left
gastric artery. The persistent root will give birth to the celiac
trunk and the other one will issue the superior mesenteric
artery. In the case where the first and the fourth root
disappear, then the celiac-mesenteric trunk will originate.
MATERIAL AND METHODS
The material for this study comprised of 16 angiography-
computed tomography (CT), performed with GE LightSpeed
VCT high image resolution 64-slice CT system and GE
LightSpeed 16- slice CT system, both systems within the
1 “Ovidius” University of Medicine and Pharmacy, Constanţa 2 ‘’Agripa Ionescu’’ Hospital, Bucharest 3 ‘’Carol Davila’’ University of Medicine and Pharmacy Bucharest 4 Arestetic Clinic Galati 5 ’’Dunarea de Jos’’ University from Galati 6 General Hospital CFR Galati
32
premises of the Clinical Emergency County Hospital “Sf.
Andrei” in Constanta. The above-mentioned 12 cases were
studied out of 2220 patients that presented for a specialist
consult for various medical reasons, during the period
between July 2012 and June 2016, in Dobrogea area of the
country, south - eastern part of Romania. From the total
number of patients, 830 were females (37.39%) and 1390
were males (62.61%). The study was conducted with respect
to the following parameters: the level of origin of the celiac-
mesenteric trunk from the aorta in relation to the vertebral
column, the trajectory and the angle formed from the origin
of the celiac-mesenteric trunk with the aortic wall, the
exterior diameter as well as the endovascular diameter of
the celiac-mesenteric trunk at the level of its aortic origin, its
length up to its bifurcation, the angle formed between its
two terminal branches as well as the diameter and the
trajectory.
RESULTS
In the present study, we met 12 cases with celiac-mesenteric
trunk (0.54% of the total cases), all male cases (0.86% of the
male cases). In relation to the vertebral column, the origin of
the trunk was located in the upper half of the L1 vertebra –
intervertebral disk between L1 and L2 vertebrae. In 7 cases
(58.33% of the cases) the origin was located at the level of
the upper half of the L1 vertebra, most frequently near the
upper margin of the vertebral body. In 3 cases (25% of the
cases), the celiac-mesenteric trunk originated in the lower
half of the L1 vertebra, whereas in 2 cases (16.67% of the
cases) it originated at the level of the intervertebral disk L1
– L2.
The celiac- mesenteric trunks originating from the aorta was
located higher than the origin of the renal arteries, at a
distance of 8.9 – 20 mm from the right renal artery,
respectively 9.2 – 22.8 mm from the left renal artery. This
indicates that the right renal artery originates most
frequently from the aorta than the left renal artery.
The celiac-mesenteric trunk originating from the aorta had
an external diameter with values ranging between 8.7 to
13.4 mm, in 8 cases (66.67% of the cases) with a diameter
ranging between 11.4 and 13.4 mm. By comparing the
external diameter of the celiac-mesenteric trunk with the
external diameter of the abdominal aorta at the level of its
origin, we have discovered differences in values, ranging
from 9.3 to 13.8 mm between the two diameters,
representing 40.09 – 58.01% of the external aortic diameter.
The aortic ostium of the celiac-mesenteric trunk had a
vertical diameter with values ranging from 8.8 to 13.1 mm –
the horizontal diameter ranged between 8.4 to 11.2 mm. In
all cases the aortic ostium had an oval shape. In 8 cases
(66.67% of the cases) the long axis was horizontal and in 4
cases (33.33% of the cases), the axis was vertical. By
comparing the vertical diameter of the aorta, the ostium
trunk had a vertical diameter with values ranging between
34.92 to 55.26% of the aortic one, whereas in the case of the
horizontal diameter it presented with values ranging
between 41.79 to 54.37% of the horizontal aortic diameter.
At the level of its origin, the celiac-mesenteric trunk created
and angle with the aortin wall, with values ranging between
30○ to 90.2○ – extreme values had been found in one for each
value, most frequent value for the angle being of 60○. This
explains the trajectory of the celiac-mesenteric trunk, most
frequently position being transverse anterolateral to the
right, an aspect met in 10 cases (83.33% of the cases) and
only 2 cases having a horizontal trajectory (transversal)
presenting with an angle of 90,2○ respectively 90,3○.
The length of the celiac-mesenteric trunk had values ranging
between 21.8 to 42.5 mm, most frequently met values
ranging from 30.7 to 33.5 mm.
The bifurcation of the celiac-mesenteric trunk into the two
arteries had an angle with values ranging from 82.2○ to
120.7○, most frequently met values being over 90○ (83.33%
of the cases). In the case that, after the bifurcation, the
superior mesenteric artery had a transverse anterolateral to
the right trajectory, the celiac trunk would always be
ascending to the right, sometimes close to a vertical position.
The celiac trunk resulting from the celiac-mesenteric
bifurcation had an external diameter with values ranging
from 6.2 to 10.2 mm, extreme values have been met in only
one case for each value; the rest of the cases with values
ranging between 8.0 to 9.2 mm. In relation to the external
diameter of the celiac-mesenteric trunk from which it
originated, the celiac trunk had an external diameter with
smaller values by 0.7 to 4.2 mm, representing 65.57 –
92.47% of its external diameter.
The length of the celiac trunk up to its ending ramification
had values ranging between 6.3 to 16.8 mm – extreme
measures were found in only one for each case. All cases
presented with a hepatosplenic trunk with the left gastric
artery originating from the abdominal aorta in 10 cases
(83.33% of the cases), at a distance of 15.1 – 18 mm above
the origin of the celiac-mesenteric trunk. In one case, the left
gastric aorta originated from the terminal bifurcation of the
celiac trunk whereas in the other case it originated from the
celiac-mesenteric trunk before its ending ramification.
The endovascular ostium of the celiac trunk had a vertical
diameter with values ranging from 7.1 to 8.6 mm, with a
Vol. CXXII • No. 2/2019 • August • Romanian Journal of Military Medicine
33
horizontal diameter of 6.6 to 8.6 mm. In 11 cases (91.67% of
the cases) the horizontal diameter was bigger than the
vertical diameter by 0.5 – 1.3 mm, thus having an oval-
shaped horizontal long axis. In only one case (8.33% of the
cases) the diameter of the ostium was bigger vertically than
horizontally, with a difference of 0.5 mm thus having an oval
shape with a vertical long axis.
The superior mesenteric artery resulted by the ramification
of the celiac-mesenteric trunk had an external diameter with
values ranging between 4.4 to 8.5 mm, smaller by 1.3 – 5.9
mm, representing 44.44 – 85.06% of the external diameter
of the celiac-mesenteric trunk.
Table: Percentage frequency of the celiac-mesenteric trunk
Author CMT frequency Differences
Adachi 2.4 % - 1.86 %
Babu 2.79 % - 2.25 %
Chen 0.7 % - 0.16 %
Eaton 0.54 % 0
Ferrari 1.7 % - 1.16 %
Jones 1.7 % - 1.16 %
Kornafel 1.5 % - 0.96 %
Lippert 3 % - 2.46 %
Lipshutz 2.4 % - 1.86 %
Matusz 0.68 % - 0.14 %
Michels 2.5 % - 1.96 %
Mu CG 0.98 % - 0.44 %
Natsume 0.60 % - 0.06 %
Nelson 2.0 % - 1.46 %
Panagouli 0.76 % - 0.22 %
Piquand 2.0 % - 1.46 %
Rio Branco 3.0 % - 2.46 %
Song 1.06 % - 0.52 %
Yadov 2.5 % - 1.96 %
Our study 0.54 % of the total cases
0.86 % male cases
The endovascular ostium of the superior mesenteric artery
had a vertical diameter with values ranging from 6.8 to 8.5
mm, with a horizontal diameter of 6.2 to 8.5 mm. In 11 cases
(91.67% of the cases) the horizontal diameter was bigger
than the vertical diameter by 0.3 – 1.1 mm, having an oval
shape with a horizontal long axis. In only one case (8.33% of
the cases) the diameters of the ostium were equal, thus
having a round shape.
By comparing the external diameters of the celiac trunk and
the superior mesenteric aorta, we have discovered that in 11
cases, the superior mesenteric aorta had a smaller diameter
than the celiac trunk, representing 47.83 – 83.33% of the
diameter of the celiac trunk and only in one case the
diameter of the celiac trunk was smaller than the one of the
superior mesenteric artery, representing 83.73% of its
diameter.
DISCUSSIONS
Analyzing the results, we had and comparing them to the
data in the existing literature referring to the morphological
characteristics of the celiac-mesenteric trunk, we have
discovered there is no thorough description of these, most
authors mentioning only the frequency as a vascular
variation.
By comparing the results of the study with the data existing
in the literature we had the possibility to consult, we
discovered that our results were the same with the results
of [1], whereas in the rest of the cases we found differences
with values ranging from 0.06 to 2.46%. Compared with the
statistics of [5, 6, 7, 8, 9, 10] our results were smaller with
values ranging between 0.06% [5] and 0.52% [10]. Compared
with [11] the results we had were smaller by 0.96% and
values ranging from 1 to 2.25% we most frequently met
[Adachi, cited by 8, 12, 13, 14, 15, 16, 17, 18, 19]. Babu [19]
is the only author mentioning the frequency of the celiac-
mesenteric trunk in both genders – our results on male cases
being smaller by 0.46%. Unlike our study where the presence
of the celiac-mesenteric trunk was met only in male cases,
Babu [19] discovers the presence of celiac-mesenteric trunk
having a wider spread within female cases (1.47% of the
cases). In relation to the statistics of [2, 3], the results are
lower, the difference being by 2.46%. Lippert [3] discovers
the presence of the gastro-hepato-spleno-mesenteric trunk
in 2% of the cases, a difference of 1.95% from our study, and
the hepato-spleno-mesenteric trunk with the origin of the
left gastric aorta from the aorta in 1% of the cases, a
difference of 0.55% from our study. Babu [19] finds that in 3
cases (15.79% of the met celiac-mesenteric trunks), the
origin of the left gastric aorta was in the celiac trunk resulted
from the celiac-mesenteric bifurcation at the level of the
abdominal aorta. In a case described by Anupama [20], from
the celiac trunk resulted the hepatic artery, the splenic
artery, the left gastric artery and a branch that participated
in formation of the gastro-duodenal artery. In the specialist
literature, we have not met celiac-mesenteric trunk cases
where the left gastric artery originated anteriorly to the
ending ramification of the celiac-mesenteric trunk, closer to
its origin.
34
The length of the celiac-mesenteric trunk given by Anupama
[20] is of 13.00 mm, Tugrul [21] specifics a length of 13.42
mm, both values being smaller than the ones we found in
our study by 8.80mm, respectively 8.38 mm smaller than the
minimum length and 29.5 mm, respectively 29.08 mm
smaller than the length we have measured in our study.
With regards to the diameter of the celiac-mesenteric trunk,
Tugrul [21] finds an external diameter of 13.98 mm, a
diameter bigger by 0.58 mm than what we have measured
for the maximum value and with 5.28mm bugger than the
minimum diameter. Compared to our results Tugrul [21]
finds the celiac trunk resulting from the celiac-mesenteric
bifurcation with a diameter (7.09 mm) bigger by 0.89 mm
from the minimum diameter and smaller by 3.11 mm from
the maximum value of the diameter we have measured. At
the level of the superior mesenteric artery Tugrul [21] finds
a diameter of 5.25 mm, bigger by 0.86 mm from the
minimum diameter and smaller by 3.25 mm than the values
of the maximum diameter we have measured in the study.
Hemanth [22] finds an external diameter of 8.7 mm for the
superior mesenteric artery, bigger by 4.3 mm than the
minimum diameter, respectively by 0.2mm than the
maximum value within our study.
CONCLUSION
There is a relatively low frequency of celiac-mesenteric trunk
cases described in the literature, our case having the lowest
frequency. The differences between different authors is
related to the number of cases they have studied and due to
the fact that cases where the hepatic artery was the only one
originating from the trunk weren’t taken into consideration
as well as the methods used for the research. There is a
difference between the classical methods (dissections,
intramuscular injections) in relation to the modern methods,
especially MDCD that has better results than the
conventional angiography [17, 23]. With modern exploration
methods, it has been noted that a greater number of
vascular variants and malformations have been observed
than those reported in the specialist literature involving
other methods. We could add as a cause to the differences
and the probable existence of some peculiarities related to
the geographical area, which exist between authors who
carried out their research on different meridians of the
world.
We consider the name of vascular malformation used by
some authors when talking about the celiac trunk is not the
correct name, whereas vascular variant seems a more
appropriate name since all vascular branches of the two
arteries are present, having the same morphological
characteristics as in the case where they originated
independently from the aorta, also because they don’t affect
the vascular territories they serve.
The present study is interesting not only for a morphologist
but also, knowing the different types of anatomical variants
is fundamental for the planning of abdominal surgical
procedure and is important to the radiologist as well, as
specified by [10, 23].
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3. Lippert H, Pabst R (1985) Arterial variations in man. Classification and frequency Ed. Bergmann Verlag, Muenchen, 46-51
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14. Michels NA (1942) The variational anatomy of the spleen and the splenic artery. Am J Anat, 70: 21–72
15. Nelson TM, Pollak R, Jonasson O, Abcraian H (1988) Anatomic
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variants of the celiac, superior mesenteric, and inferior mesenteric arteries and their clinical relevance. Clin Anat, 1: 75–91
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Article received on April 3, 2019 and accepted for publishing on June 3, 2019.
ORIGINAL ARTICLES
Local treatment options for management of loco-regional esophageal squamous cell carcinoma
Tülay Eren1, Gökşen İ. İmamoğlu1, Fatih Yildiz2, Süheyla A. Arslan3, Sultan A. Kocacan1, Salih Z. Çakar4, Ozan Yazici4, Doğan Yazılıtaş1, Nuriye Özdemir3, Berna Öksüzoğlu2
Abstract: Aim: Surgical treatment is the main treatment method for esophageal cancer. The prognosis is poor due to high local recurrence and distant metastasis rates. Study aims to evaluate the most effective local treatment modality esophageal squamous cell carcinoma (SCC) according to real life data.
Method: 136 patients were studied retrospectively. All patients were middle or lower esophageal cancer and had the SCC histology. Patients were divided into the surgical resection, definitive CRT (dCRT), and multimodal treatment groups according to curative local treatment they received.
Result: 32.4% were in the surgical, 36% were in the dCRT, and 31.6% were in the multimodal group. Median disease-free survival was 21 months (95% CI 14-27) in the surgical group, 8 months (95% CI 4-11) in the dCRT group, and 18 months (95% CI 0-39) in the multimodal group (p=0.059). The median overall survival was found to be 40 months (95% CI 0-92) in the surgical group, 19 months (95% CI 15-22) in the dCRT group, and 54 months (95% CI 11-96) in the multimodal group (p=0.012). In multimodal group, the number of patients receiving preoperative CRT was 25, and postoperative CRT was 18. Median OS was 47 months (95% CI 0-99) in the preoperative CRT group, and 64 months (NA) in the postoperative CRT group (p=0.302).
Conclusion: DFS and OS contributions of multimodal treatment in esophageal SCC have been shown in the present study. The addition of CRT to surgery in the preoperative or postoperative period has a contribution independently of the treatment sequence.
Keywords: multimodal treatment, surgery, definitive chemoradiotherapy, squamous cell, esophagus cancer
INTRODUCTION
Esophageal cancer is the seventh most common cause of
cancer-related deaths worldwide. In 2012, 455,800 people
were diagnosed with, and 400,200 people died from
esophageal cancer [1].
Surgical resection has traditionally been the primary
treatment for esophageal cancer in order to maintain local
disease control and prolong life expectancy. The median
survival is 15-18 months, and the 5-year survival rates are
20-25% after esophagectomy [2].
Failure in the treatment is generally due to recurrence and
metastases. Developments in standard therapy are ongoing.
Radiotherapy can provide locoregional control in esophageal
cancer, while chemotherapy has both local and systemic
antineoplastic effects. With the development of
multidisciplinary treatment approaches, the use of
1 Dışkapı Yıldırım Beyazıt Research and Education Hospital, Ankara, Turkey 2 Ankara Onkoloji Research and Education Hospital, Ankara, Turkey 3 Yıldırım Beyazıt University, Ankara, Turkey 4 Numune Research and Education Hospital, Ankara, Turkey
Corresponding author: Tülay Eren
Vol. CXXII • No. 2/2019 • August • Romanian Journal of Military Medicine
37
chemoradiotherapy (CRT) in addition to surgery has become
the most frequently used treatment method [3].
In esophageal cancer treatment, the results obtained from
surgical treatment alone are not satisfactory in terms of
locoregional recurrence or distant metastasis rates. This has
paved the way for multimodal treatment approaches.
Together with the multimodal treatment,
chemoradiotherapy (CRT) added to surgery in the
preoperative or postoperative period, aims to provide
disease-free survival and an increase in life expectancy.
Preoperative chemoradiotherapy has begun to be used to
increase the R0 resection rates by reducing the tumor stage
before surgery, thereby contributing to survival [4-10]. The
application of surgery after preoperative
chemoradiotherapy is now a well understood and effective
treatment [11, 12]. In the ChemoRadiotherapy for
Oesophageal cancer followed by Surgery Study (CROSS), a
pilot study related to preoperative chemoradiotherapy, the
preoperative chemoradiotherapy was reported to increase
the median OS approximately 2-fold when compared to
surgical treatment alone (49.4 vs 24.0 months) [4].
In the literature, there are data about the postoperative
(adjuvant) activity of chemo-radiotherapy in addition to its
preoperative activity. In the past, the major problem in
applying chemoradiotherapy in the postoperative period
was the inability of patients to complete the scheduled
treatment due to poor performance of the patients after
surgery, but currently developing surgical and radiotherapy
techniques have partly removed this problem. Studies by
Rice et al. [13] and Bedard et al. [14] have demonstrated the
survival advantage of postoperative CRT. In the
retrospective study by Rice, the median survival was stated
to be 28 months with surgical postoperative CRT, and 15
months with surgery alone (p<0.05). In the study by Bedard,
the median overall survival was reported to be 47.5 months
with postoperative CRT and 14.1 months with surgery alone
(p=0.001) [14].
Following the studies showing the benefits of preoperative
and postoperative chemoradiotherapy, studies about
treatment sequence emerged. Current data on the
prognostic effect of local treatment sequence in esophageal
cancer remain controversial [15, 16]. In a study based on the
SEER data, it was determined that preoperative CRT ensured
better survival compared to postoperative CRT [15], while a
prospective study reported no difference in survival
between taking the CRT in the preoperative or postoperative
period [16].
In the light of this information, the prognostic implications
of optimal multimodal treatment, surgery and chemo-
radiotherapy sequence in the treatment of esophageal
cancer are still controversial. No standard guideline has been
created in this particular. The main aim of this study was to
evaluate the most effective local treatment modality in non-
metastatic, middle and lower esophageal squamous cell
carcinoma (SCC) according to real-life data.
METHODS
A total of 136 patients diagnosed between the years 2005-
2016 in 3 different oncology clinics were included in the
study. The patient data were reviewed retrospectively.
Patients aged 18-70 years, without distant metastasis,
treated for curative purposes, with ECOG performance
status 0-2, with appropriate liver/renal reserve, middle and
lower esophagus involvement, and with SCC histology were
included in the study. Patients with adenocarcinoma
histopathology, with cervical esophagus involvement, and
those who only received RT as a local treatment were not
included in the study.
All the patients were applied with thorax and entire
abdomen computed tomography (CT) or positron emission
tomography (PET-CT) or endoscopic ultrasonography (EUS)
examinations for the purpose of staging prior to local
treatment. The patients were divided into 2 groups as local
and local advanced disease according to the radiological
results at the time of diagnosis. Radiologically, patients with
T4 tumors or lymph node positivity were considered to have
locally advanced disease, while non-T4 patients with lymph
node-negativity were considered to have local disease.
The patients were divided into 3 groups as those who
underwent only surgical resection, only definitive CRT
(dCRT), and multimodal treatment (preoperative CRT or
postoperative CRT) according to the curative local treat-
ments they received and were evaluated comparatively.
Platinum-based combination therapies (fluorouracil or
taxane) were administered concomitantly with the chemo-
therapy regimen in patients receiving chemoradiotherapy.
In CRT planning, a 3 mm interslice distance CT scan was
performed on all patients in the supine position. In patients
undergoing definitive and preoperative chemoradiotherapy,
the gross tumor volume (GTV) was determined for primary
mass and involved lymph nodes using thoraco-abdominal
CT, PET-CT, endoscopy and EUS information, if available. The
clinical target volume (CTV) was established by giving a
margin of 4 cm in the superior-inferior direction and 1 cm in
the radial direction to the primary mass. The planning
volume was obtained by allowing 1 cm extra margin to this.
The spinal cord, lungs, and organs at risk, such as the heart,
remaining within the area were contoured. In postoperative
38
therapy, bilateral supraclavicular or celiac lymph nodes were
included in the area in the location of all mediastinum and
primary masses.
The gastroesophageal intersection and proximal stomach
were included in the area in distal localized tumors.
The radiotherapy (RT) plans were made by applying the 3-
dimensional conformal technique. Patients undergoing
definitive CRT (dCRT) received a total of 50.4 Gy
radiotherapy, and those undergoing pre-operative or
postoperative CRT received a total of 45 Gy radiotherapy,
which was applied as 1.8 Gy daily for 5 days a week.
All patient records were reviewed clinically, pathologically
and in terms of treatment characteristics. The long-term
survival data of patients were obtained from the patient files
and from the data of the Turkish civil registry office.
Approval for the study was granted by the Ethics committee
of Sağlık Bilimleri University Dışkapı Yıldırım Beyazıt Training
and Research Hospital.
The data were analyzed using SPSS 18.0 for Windows
software. Descriptive statistics were expressed as mean ±
standard deviation or median (minimum-maximum) for non-
continuous numerical variables, and as number (n) and
percentage (%) for categorical variables.
The progression and overall survival rates of all cases were
investigated using Kaplan-Meier survival analysis. The 2-year
and 3-year cumulative progression and overall survival rates
together with mean lifespan and 95% confidence intervals
for these terms were calculated. The demographic
characteristics of the patients were assessed using
descriptive statistical methods. Parameters that were
significant in univariate analysis were assessed using Cox
regression multivariate analysis. A value of p<0.05 was
accepted as statistically significant.
RESULTS
A total of 136 patients were evaluated comprising 32.4%
(n=44) in the surgical group, 36% (n=49) in the definitive CRT
(dCRT) group, and 31.6% (n=43) in the multimodal treatment
group. Of the total patients, 52.2% were female and 47.8%
were male.
The demographic characteristics of the patients are shown
in Table 1.
Table 1: Demographic characteristics of the patients
Surgery (n=44)
dCRT (n=49)
Multimodal Treatment
(n=43) p Value
Age (years) Median (min-max) 52 (32-76) 58 (25-77) 50 (32-70) 0.001
Gender Female 26 (59.1%) 21 (42.9%) 24 (55.8%)
0.249 Male 18 (40.9%) 28 (57.1%) 19 (44.2%)
Smoking Smokers 20 (45.5%) 26 (53.1%) 12 (39.5%)
0.426 Non-smokers 24 (54.5%) 23 (46.9%) 26 (60.5%)
Alcohol Use Users 15 (34.1%) 14 (28.6%) 19 (44.2%)
0.288 Non-users 29 (65.9%) 35 (71.4%) 24 (55.8%)
Comorbid disease Present 15 (34.1%) 16 (32.7%) 8 (18.6%)
0.208 Absent 29 (65.9%) 33 (67.3%) 35 (81.4%)
Cancer history in family
Present 9 (20.5%) 14 (28.6%) 9 (20.9%) 0.581
Absent 35 (79.5%) 35 (71.4%) 34 (79.1%)
Tumor Grade
Well 2 (4.5%) 5 (10.2%) 4 (9.3%)
0.240 Moderate 8 (18.2%) 6 (12.2%) 5 (11.6%)
Poor 3 (6.8%) 12 (24.5%) 4 (9.3%)
Location of tumor
Mid-esophagus 18 (40.9%) 25 (51.0%) 25 (58.1%) 0.271
Lower esophagus 26 (59.1%) 24 (49%) 18 (41.9%)
Pre-clinical stage Early 26 (59.1%) 11 (22.4%) 20 (46.5%)
0.001 Locally advanced 18 (40.9%) 38 (77.6%) 23 (53.5%)
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39
When the postoperative stages of 44 patients treated with
surgery alone were evaluated, it was seen that 15.9% (n=7)
of these patients were stage 1, 40.9% (n=18) were stage 2,
and 43.2% (n=19) were stage 3. Adjuvant chemotherapy
with cisplatin/fluorouracil combination was administered to
27.3% (n=12) of the patients in this group.
One patient died in the intensive care unit due to surgical
complications in the postoperative period.
In the group of patients receiving definitive CRT, 1 patient
died due to complications during treatment.
The number of patients receiving preoperative CRT was 25
and the number of patients receiving postoperative CRT was
18 in the multimodal treatment group. In the multimodal
treatment group, a pathological complete response was
determined in 64% (n=16) preoperative CRT group. In this
group, 4 patients died in the postoperative period due to
complication. In postoperative CRT group, 11.1% (n=2) of the
patients were stage 1, 16.7% (n=3) were stage 2, and 72.2%
(n=13) were stage 3 after surgery.
The median follow-up time was 31 months (2-142) in the
surgical group, 11 months (2-106) in the definitive CRT
group, and 20 months (4-140) in the multimodal treatment
group.
The median disease-free survival was 21 months (95% CI 14-
27) in the surgical group, 8 months (95% CI 4-11) in the
definitive CRT group and 18 months (95% CI 0-39) in the
multimodal treatment group (p=0.059). DFS curve shown in
Figure 1.
Figure 1: Disease Free Survival
The 2-year disease-free survival (DFS) was 43% in the surgical
group, 33% in the definitive CRT group, and 47% in the
multimodal treatment group (p=0.05).
The median overall survival (OS) was 40 months (95% CI 0-
92) in the surgical group, 19 months (95% CI 15-22) in the
definitive CRT group and 54 months (95% CI 11-96) in the
multimodal treatment group. The difference between the
groups was statistically significant (p=0.012). Cumulative OS
curve shown in Figure 2.
The 2-year OS was 68% in the surgical group, 40% in the
definitive CRT group and 59% in the multimodal treatment
group (p=0.01).
In the multimodal treatment group, the median OS was
found to be 47 months (95% CI 0-99) in the preoperative CRT
group, and 64 months (NA) in the postoperative CRT group.
The difference between the groups was not statistically
significant (p=0.302). OS curve when the multimodal group
was divided into two as preoperative and postoperative CRT
shown in Figure 3.
DISCUSSION
Surgical resection is the basic method that is conventionally
effective in providing local disease control in non-metastatic
esophageal cancer treatment. However, due to high
locoregional recurrence and distant metastasis rates,
surgical resection alone is insufficient. The median overall
40
survival after esophagectomy is 15-18 months and the 5-
year survival rate is 20-25% [2].
Figure 2: Overall Survival
Figure 3: Overall survival in definitive chemoradiotherapy group
In a study by Orringer et al. conducted on 800 patients, the
5-year survival rates after esophagectomy were reported
23% [17]. In another study in which the surgery was
compared with surgery after preoperative CRT, and patients
were evaluated in the early stage, the median OS was
reported as 18.6 months in the patients who underwent
surgery [9].
In the present study, the disease-free survival was 21
months and the overall survival was 40 months in the group
of patients who underwent surgery alone. In the surgical
group, 27.3% of the patients (n=12) received adjuvant
chemotherapy with Cisplatin/Fluorouracil combination.
Compared to general literature data, the patients included
in the current study had longer DFS and OS. Possible reasons
Vol. CXXII • No. 2/2019 • August • Romanian Journal of Military Medicine
41
for this may be the exclusion of upper esophageal tumors,
which are known to have a worse prognosis, and the fact
that approximately 25% of the patients who underwent
surgery were administered adjuvant chemotherapy.
Although surgical resection is still the basic standard
approach in non-metastatic esophageal tumors, definitive
chemoradiotherapy is still an effective local treatment
alternative for patients not suitable for curative surgery [18].
In one of the largest studies in which a direct comparison
was made between definitive chemoradiotherapy and
surgery, the two-year survival rates were 45.4% in the
definitive CRT group and 56.2% in the surgical group [19].
This study supports the idea that all patients who cannot
undergo surgery due to high risk may be recommended
definitive chemoradiotherapy independent of the histology.
In the present study, the definitive CRT group showed a
disease-free survival of 8 months, an overall survival of 19
months, and a 2-year survival rate of 43%. These results are
consistent with the literature.
Although surgical resection is the curative treatment
approach for esophageal cancer, the poor long-term survival
outcomes have encouraged multimodal treatment
approaches in this patient group. With preoperative
chemoradiotherapy as one of the multimodal treatment
methods, the treatment of micro metastases and regression
of the tumor stage contribute positively to the overall
survival rates of patients by increasing the rate of curative
resection [4-10].
In the CALGB 9781 study, the median survival was 4.4 years
vs. 1.7 years (p=0.002) and 5-year survival rates were
reported to be 39% vs 16% in favor of multimodal treatment
in esophagectomy after preoperative CRT, where the
cisplatin/fluorouracil combination was used compared with
esophagectomy only [10]. In the CROSS trial, patients who
underwent surgery after preoperative chemoradiotherapy
and patients who underwent surgery only were compared.
The concomitant paclitaxel-carboplatin combination was
used in this study. It was reported that the preoperative CRT
improved the survival times compared to the surgery group
(OS 49.4 months vs 24.0 months, HR for survival, 0.657; 95%
CI, 0.495-0.871; p=0.003) [4]. The long-term results of the
CROSS trial also showed that the contribution to overall
survival continued [12].
Another multimodal treatment approach is postoperative
adjuvant CRT. Many studies have shown the contribution to
survival of postoperative chemoradiotherapy in patients
who have undergone esophagectomy [13, 14, 20, 21, 22, 23].
In a study by Hwang et al., the 3-year OS rates in squamous
cell esophageal cancer were 44.9% in patients who
underwent postoperative CRT after esophagectomy, and
28.1% in patients who underwent surgery alone [20].
Following studies showing the contribution of preoperative
and postoperative CRT in esophageal cancer, questions were
asked about the prognostic contribution of surgery and the
sequence of chemoradiotherapy and what should be the
optimal treatment sequence. In a prospective study by Lv et
al., where preoperative CRT, postoperative CRT, and surgery
were compared, both 5-year OS (43.5% vs 42.3%) and 5-year
DFS (37.5% vs 37.2%) were found to be similar between the
preoperative CRT and postoperative CRT groups (p>0.05)
[16]. Chen et al. emphasized that CRT together with surgery
extended the overall survival independently of the
treatment sequence [24].
In a retrospective study in which Hsu et al. evaluated the
optimal treatment sequence for locally advanced
esophageal cancer in 2017, the preoperative CRT and
postoperative CRT groups were found to have similar
median OS (26 vs 23 months, p=0.31) [25]. A statistically
insignificant but clinically significant difference was found in
disease-free survival (16.7 months vs 10.4 months, p=0.061).
However, in that study, the rate of stage 3 patients was
higher in the group receiving postoperative CRT.
Based on this information, in the present study, the
multimodal treatment group was found to be superior to
patients who underwent surgery only or definitive CRT in
terms of both overall survival and disease-free survival. The
treatment sequence in the multimodal group was not found
to affect the overall survival and disease-free survival and
these results are consistent with the current literature.
Since the present study was retrospective, it has some
limitations. As patients from three different oncology clinics
were included, it was not possible to obtain information on
which criteria the patients were directed to different
treatment groups when the initial treatment plan was made.
No information could be obtained about why the patients
with local disease could not be operated on. The fact that
patients undergoing surgery were operated on by different
surgical clinics was another limitation. Not all toxicity data
could be obtained due to the retrospective nature of the
study.
In conclusion, it was determined that the multimodal
treatment of squamous cell medium and lower esophageal
tumors increased the disease-free survival and overall
survival, but the treatment sequence had no effect in this
particular. However, there are questions that still need to be
answered for operable esophageal tumors, such as what the
ideal local treatment modalities and combinations are,
whether it is preferable to apply the chemotherapy scheme
42
synchronously with CRT, and the location of postoperative
adjuvant chemotherapy. There is a need for further
randomized phase studies on these subjects.
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Article received on April 10, 2019 and accepted for publishing on June 23, 2019.
ORIGINAL ARTICLES
Methods of assessing stable coronary artery disease by non-invasive imaging techniques
Carmen M. Voicu1, Tiberiu Nanea2
Abstract: Diagnosis of stable coronary artery disease is vital for prognosis, classification and early treatment. Current guidelines show that patients with stable angina who are suspected of CAD need to undergo a certain protocol for classification and further analysis. This review’s aim is to present the most used non-invasive techniques for identification of CAD and to underline the current development of imaging technology and the possible reduction of invasive measures due to non-invasive techniques.
Currently, non-invasive techniques used to diagnose stable coronary artery disease have a very high accuracy and newer methods seem to be comparable to the gold-standard. The majority of the methods discussed have an optimal performance for patients with PTP between 15-85%, and the future of diagnosis for these patients seem to involve less invasive measures and less radiation by improving the current devices and by usage of machine-learning algorithms.
Keywords: coronary artery disease, PTP, stress echocardiography, SPECT, CMR, CCT
INTRODUCTION
Diagnosis of stable coronary artery disease is vital for
prognosis, classification and early treatment. Failure in doing
so, might determine secondary events such as: disease
progress, myocardial infarction or even death.
Current guidelines show that patients with stable angina
who are suspected of CAD need to undergo a certain
protocol for classification and further analysis.
This review’s aim is to present the most used non-invasive
techniques for identification of CAD and to underline the
current development of imaging technology and the possible
reduction of invasive measures due to non-invasive
techniques.
METHODS
A PubMed review was performed, analyzing all publications
from 1968 to 2019 concerning the topic “stable coronary
artery disease” (keywords: coronary artery disease, PTP,
stress echocardiography, SPECT, CMR, CCT). Human studies
and meta-analyses, published in English, were cited in this
review.
RESULTS AND DISCUSSION
Diagnosis and management
According to current guidelines, patients with suspected
SCAD will follow a step-by-step approach for confirmation.
After the clinical examination and basic tests applied (ECG,
bio-chemistry indicators, resting echocardiography), if the
cause of chest pain is none other than CAD and the left
ventricle ejection fraction is higher than 50%, the evaluation
of suspected SCAD commences (patients with LVEF<50%
have a high risk for cardiovascular events and they should
have ICA without further testing). [1]
First step is to determine the pre-test probability of SCAD
1 Clinical Emergency Hospital Bucharest, Romania 2 Prof. Dr. Th. Burghele” Hospital, Bucharest, Romania
44
(PTP). This indicator is evaluated by the age, gender and the
nature of symptoms for the suspected patient, and evaluates
the probability of having a coronary artery disease before
realizing any tests.
Non-invasive imaging techniques that assess coronary artery
disease usually have sensitivities and specificities around the
value of 85% (coronary computed tomography angiography
– coronary CTA has the highest sensitivity (95%) [2] while
stress echocardiography has the highest specificity (94.6%)
[3]). This is why for 15% of the patients, most imaging
techniques will be false positive and therefore, for these
patients (with PTP < 15%) performing no non-invasive
imaging tests will bring less incorrect results. Therefore:
patients with PTP < 15% will not do any further
investigations;
patients with PTP between 15-65% are recommended to
have an exercise ECG as the initial test and afterwards if
necessary, perform imaging tests;
patients with PTP between 66-85% must have a non-
invasive imaging test for confirmation;
patients with PTP over 85% are assumed to have SCAD, so
they don’t need further investigations. [1]
As such, patients with PTP between 15%-85% are required
to be assessed with non-invasive techniques for risk
stratification and selection for invasive measures
(revascularization or ICA). [4]
Electrocardiogram exercise testing
As described above, for patients with PTP within 15-65% for
suspected SCAD, an exercise electrocardiogram will be the
first and best option.
According to the Bruce protocol, this test involves using a
treadmill or an exercise bicycle in which patients are
monitored using a continuous 12-lead ECG and their blood
pressure measured, when they are exercising. The level of
difficulty increases incrementally every 3-minutes until a
certain target is reached (the predicted heart rate for the age
of the patient) or the patient cannot continue the test. [5]
If ST-depression is present with a value of ≥ 0.1mV or 1 mm,
in one or more ECG leads, which persist at least 0.06-0.08
seconds after the J-point, the test detects a possible CAD. [1]
Data shows that the usefulness of the test might come for its
higher specificity, one study shows a sensitivity of 45%, and
specificity of 85% [6] while another study shows higher
values for men (sensitivity – 40%, specificity – 96%) than for
women (sensitivity – 33%, specificity – 89%). [7]
Also, in a meta-analysis which compared the efficacy of
exercise stress testing between 34 studies, results also
showed that for men a positive exercise test results in a 89%
probability of CAD, and for women results in a 69%
probability of CAD. Whereas, a negative exercise test leads
for men to a 37% probability of CAD and for women to an
18%. These values show that a large share of patients may
be undetected after performing an exercise stress test. [8]
This method is useful only for patients that don’t have ECG
abnormalities at baseline. For example, patients with Wolff-
Parkinson-White syndrome, paced ventricular rhythm, LBBB,
use of digitalis, atrial fibrillation, left ventricular hypertrophy
with repolarization changes or digoxin use, have a higher
likelihood that the observed ST-segment depressions would
happen because of the baseline pathology and not the CAD.
Therefore, in these patients the ECG results aren’t
interpretable and exercise ECG testing should not be
performed. [9]
Despite all the results, for low-risk patients, for example
women, the standard ECG exercise treadmill test should be
the first diagnostic strategy, because of its availability and
lower costs of usage. Additional imaging techniques, like
myocardial perfusion imaging (MPI) does not add any
substantial benefit to the exercise treadmill test, but
increases diagnostic costs significantly [10].
Also, it is safe to say that during exercise testing, the risk of
having myocardial infarction because of the increase in the
pro-coagulant activity, doesn’t increase for patients with
CAD (objectified angiographically) in comparison to those
who don’t have CAD, meaning that the method is in general
safe. [11]
Although this method is accessible for diagnosis of CAD, in
the near future it will probably be replaced with other more
accessible, non-invasive imaging techniques. Cardio-
goniometry (3D-ECG) was demonstrated to have a higher
performance in diagnosis (sensitivity 75% vs sensitivity
68.1% - exercise ECG and specificity 74.4% vs specificity
38.1% - exercise ECG) of CAD in women, and being able to
have this efficacy without having to undergo stress-testing
and being practically free-of-risk, surely proves an
improvement in easiness and performance in the diagnosis
of CAD for the near future. [12]
Stress echocardiography
Another imaging technique for the assessment of stable CAD
is stress echocardiography. This method usually involves a
mechanical stressor (exercise performed on a treadmill or a
bicycle) or a pharmacological agent.
The principle of stress echocardiography is the identification
of functionality for all cardiac walls and further classification
into normal, ischaemic, viable or necrotic myocardium:
Vol. CXXII • No. 2/2019 • August • Romanian Journal of Military Medicine
45
- normal myocardium responds with normokinetic function
at rest and during stress it may have a normokinetic or
hyperkinetic function;
- ischaemic myocardium may have a normal function at rest,
but during stress its response worsens, having a
hypokinetic/akinetic/dyskinetic function;
- viable myocardium testing in dysfunctional myocardium at
rest shows a improvement during stress response because it
would indicate a region of hibernating myocardium that
improves its function after revascularization;
- necrotic myocardium doesn’t improve its function during
stress, a region of dysfunctional myocardium at rest has its
function fixed. [13]
Stress echocardiography using exercise stress is preferable
because it provides additional data like exercise time,
workload, heart rate and blood pressure variability.
Pharmacological stress using dobutamine can be used for
patients who are unable to exercise. [1]
Also using dobutamine bring the advantage of assessment of
viability more accurately than exercise stress
echocardiography. Ischaemic but viable myocardium at low
doses of dobutamine (10-20 μg/kg/min) improves its
function, but at high doses (40 μg/kg/min) its function
worsens. This effect is due to the initial inotropic function of
dobutamine at low doses, whereas in high doses its function
changes to chronotropic and especially vasodilatory. [14]
Using additional contrast to the method (by using
microbubbles of encapsulated gas) can bring enhancement
of the images viewed, by improving image quality, accuracy
of detection of CAD and reader confidence, especially when
certain segments cannot be visualized at rest. [15]. Newer
data show data coronary microvascular dysfunction (a
potential cause for chest pain) can be observed using
myocardial contrast echocardiography, a marker for possible
CAD, patients with this issue having lower hyperemic
perfusion and microvascular flux rate than patients with
normal microvascular function. [16]
Diagnosis of CAD using stress echocardiography is quite
efficient. Exercise stress echo, dobutamine and dipyridamole
stress echo show sensitivities of 85%/80%/78% and
specificities of 77%/86%/91% for detection of CAD, which
are significantly better than electrocardiogram exercise
testing, and similar to SPECT [17]
Also, using strain-rate imaging and tissue Dopple imaging
can improve the quality of detection for CAD. Because the
interpretation of images in most echocardiographies are
subjective and prone to errors, measuring strain-rate can
determine an objective view on the diagnosis. Voigt et al
showed that ischemic segments had significantly higher peak
systolic strain-rates and strains during ejection time during
dobutamine stress than nonischemic segments [18] and
Gupta et al., recently showed in a meta-analysis similar
results, analysis of longitudinal strain imaging having higher
AUC-ROC prediction of CAD (0.92) than assessment of wall
motion (0.83). [19]
The newest advancement in echocardiography for detecting
CAD markers is the 3D-speckle tracking echocardiography
(3D-STE). One of the most used scoring systems to objectify
CAD severity is the Gensini score. In one study, using 3D-STE
to measure 4 parameters of CAD (global longitudinal strain –
GLS, global circumferential strain – GCS, global radial strain
– GRS and global area strain – GAS) it had been found that
patients found with critical CAD after coronary angiography
had significantly worse values of GLS,GCS,GRS,GAS than
patients with noncritical CAD. Also the Gensini score had a
significant positive linear correlation with GLS and GAD,
meaning that 3D-STE was a very good method do identify the
grade of severity of CAD. [20]
SPECT (Single photon emission computed tomography) –
Myocardial perfusion scintigraphy
One of the most used imaging techniques, uses similar
principles like the previously described methods. It uses
either exercise stress or pharmacological stress (e.g.
adenosine, dipyridamole, dobutamine, regadenoson) and
measures the level of uptake of radioactive tracers at rest
level and stress level from the myocardium. In ischemic
tissue, due to the lower blood flow in stress response, the
uptake of the tracer is reduced, meaning a positive test for
diagnosis of CAD. [4]
Standard radiotracers are Technetium-99m (99mTc) or
Thallium 201 (201Tl), although the latter has a higher
radiation dose. New developments in this technology
(cadmium-zinc-telluride – CZT) show a significantly higher
performance than conventional SPECT and a lower dose of
radiation. [21] Also another radiotracer (for PET) that is
frequently used is Rubidium 82 (82Rb) that is associated with
lower radiation exposure and high sensitivity (82%) and
specificity (90%) for detecting ischaemia. [22]
The method also compares ischaemic areas of myocardium
to normal areas. Some patients (with triple vessel disease)
whom hearts have a widespread ischemia, will be detected
false-negative for CAD because of the lack of inducing
ischemia in the underperfused myocardium, proving a
limitation of the method. [23]
Another limitation of the method would be diagnosis of CAD
in patients with left bundle branch block (LBBB). In those
patients, the intraventricular septum has a delay in
46
contraction (being dyskinetic), and in the moment of image
acquisition may have a lower thickness, indicating a LAD
territory ischaemia, and thus a false-positive result. [24]
Also, for asthmatic patients that are undergoing SPECT, using
adenosine is a contraindication because of the possible
precipitation of bronchospasm due to activation of all
adenosine receptors (especially A1, A2B and A3).
Regadenoson, a selective A2A agonist (for producing
hyperaemia) is currently used for these patients, because of
its sufficient hyperaemic response, less side effects, and
comparable efficacy to adenosine. [25]
The REASSESS study, in which in a prospective manner was
assessed the diagnostic performance of coronary computed
tomography angiography (CTA) vs. SPECT, showed that
although many cases of stable CAD wouldn’t have been
diagnosed by SPECT if invasive measures (angiography)
wouldn’t have been taken, the overall performance of both
of the methods (CTA and SPECT) was similar, in objectifying
hemodynamically significant stenosis, having a similar
accuracy (70% - CTA vs. 68% SPECT). [26]
The issue of false-negative results in SPECT, although
present, is indicated to have a low prevalence and thus, a
low impact. For example, in 133 patients with normal SPECT
results, only 16% had anatomically and functionally
significant stenoses, and from 180 vessels analyzed with
normal SPECT results, only 8.33% had stenoses. As such, the
prevalence of false-negative cases in normal SPECT remains
low and a normal result stays important in diagnosis and
follow-up. [27]
SPECT also predicts efficiently long-term outcomes. Patients
with ischaemia burden, who had SPECT and also underwent
early coronary revascularization had significantly lower all-
cause mortality and cardiac mortality in comparison to
patients who received only pharmacological therapy,
indicating a significant diagnostic value for the severity of
CAD by using SPECT. [28]
Usage of myocardial perfusion scintigraphy combined with
positron emission tomography is more accurate in
comparison to SPECT, having higher sensitivities (90% - PET,
85% - SPECT) and higher specificities (88% - PET, 85% -
SPECT), also AUC-ROC prediction was higher for PET (0.95) in
comparison to SPECT (0.90), according to Mc Ardle et al. [29]
A similar study showed better image quality and diagnostic
accuracy of CAD for PET in comparison to SPECT (showing a
percentage of 78%/79% excellent image quality of
rest/stress PET scans vs. 62%/62% excellent image quality of
rest/stress SPECT scans). [30]
Data also shows that using PET-MPI to determine myocardial
blood flow is excellent and superior to the relative
measurement of tracer uptake, being more efficient for the
detection of CAD and eliminating false-negative patients
with balanced ischaemia (triple vessel disease). [31]
New technology in PET-MPI for diagnosis of CAD show
similar results as described above, for usage of flurpiridaz 18F
in comparison to SPECT, bringing more advantages for PET-
MPI (higher quality images, diagnostic certainty of
interpretation, and sensibility of detection of CAD). [32]
Cardiac magnetic resonance
One of the most advantageous methods of imaging
techniques, because of the high-detail images, non-
invasivity and lack of any ionizing radiation, cardiac magnetic
resonance can identify CAD, even better than the previous
methods discussed. Similar to all CAD detection methods, is
uses a stress agent, exercise or pharmacological.
Stress cardiac magnetic resonance using both a bicycle [33]
and a treadmill [34] seems feasible for detection of CAD.
Recently, the EXACT study, which used stress CMR with a
treadmill, showed a sensitivity of 79% and a specificity of
99% for detection of CAD after using a SPECT, also showed
higher agreement of diagnosis with angiography (k=0.82)
than SPECT (k=0.46), demonstrating as such excellent
diagnostic value. [35]
Pharmacological stress uses a vasodilator (adenosine or
regadenoson) or dobutamine. Added in the vasodilator
method is the administration of i.v. gadolinium contrast, to
enhance the perfusion defects that can be seen in ischaemic
walls. Using dobutamine requires a similar method like in
stress echocardiography, by viewing wall motion
abnormalities in ischaemia response. [36]
In CMR the assessment of CAD can be either qualitative (by
visual assessment of presence and degree of ischaemia) or
quantitative by measuring absolute blood flow. A recent
study showed that quantitative analysis had similar
diagnostic accuracy (83%) as qualitative (80%) and observers
considered a better approach to diagnose CAD using
quantitative CMR. [37]
Recent data showed that CMR stress with perfusion in
comparison with SPECT and PET showed good diagnostic
accuracies, having a sensitivity of 89% (in comparison to
SPECT – 88%, and PET – 84%) and a specificity of 76% (in
comparison to SPECT – 61% and PET – 81%). Authors also
considered that CMR could be a good alternative to PET,
having a similar diagnostic accuracy. [38]
Nevertheless, current data shows that perfusion CMR has a
better diagnostic performance value than SPECT, as shown
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47
in the MR-IMPACT trial [39]. Also, the CE-MARC study
showed that CMR had better sensitivities than SPECT (88.7%
for men vs. 50.9% for men – SPECT and 85.6% for women vs.
70.8% for women – SPECT) and similar specificities, and
better diagnostic accuracies. [40]
The CE-MARC 2 study compared the efficacy of CMR, NICE
guidelines and SPECT in reducing the percentage of
unnecessary angiographies in patients with suspected
angina. The results showed that the CMR strategy
determined a lower probability of unnecessary
angiographies within 12 months than the NICE guidelines
strategy, CMR and SPECT reducing significantly the number
of angiographies in comparison to NICE guidelines. [41]
The adverse effects for gadolinium-based contrast agents
used in CMR have a low frequency (0.36%), the severe are
even less (0.033%), and these adverse effects are more
physiological than allergic (most frequently were dyspnea,
hypersensitive reactions and emesis). [42].
Similar to SPECT, it had been shown that CMR can have long-
term prediction values. Newer technology in CMR measures
GLS (global longitudinal strain), this marker can be an
independent predictor for long-term major adverse cardiac
events (MACE): heart failure hospitalization, myocardial
infarction, sustained ventricular tachycardia or death, in
pacients with known or suspected coronary artery disease.
That means CMR can identify patients with high risk of
having dangerous adverse events in the near future because
of CAD. [43]
Also, the newest data shows that CMR with quantitative
myocardial perfusion mapping can detect coronary
microvascular dysfunction separately from CAD, with high
AUC-ROC prediction values (0.95 on vessels with MVD) with
high sensitivity (90%) and specificity (89%), almost
comparable with invasive procedures. [44]
More powerful magnets (3.0 Tesla), although not so widely
available, used on CMR machines, have a net superiority
over 1.5 Tesla CMR, having a far greater AUC-ROC prediction
value (0.963 vs 0.645), sensitivity (90.5% vs. 61.9%) and
specificity (100% vs. 61.9%). [45]
Computed tomography
Multidetector row CT systems used in cardiac CT are
sufficient enough to visualize coronary anomalies, although
this last method is preferable for measuring coronary
anatomy and pathology occurring in this matter. There are
two methods of using CT in the benefit of diagnosis for CAD:
calcium scoring and CTCA (coronary computed tomography
angiography).
Calcium scoring uses the principle of identifying coronary
calcification, without use of contrast. Any pixel above 130
Hounsfield units is defined as coronary calcification and can
be quantified using the Agatston score, which is dependent
by the size of the plaque and the radiographic density. [46]
However, there can be identified obstructive coronary
lesions which may be not calcified and vice-versa, critically
calcified coronary arteries which aren’t yet obstructed.
Because of this matter, the preferable way to diagnose CAD
is CTCA.
The North American Society for Cardiovascular Imaging
(NASCI) agreed in their guidelines that patient selection is
needed before usage of CTCA. As such:
- because of contrast usage, any patients with known
history of severe anaphylactic reactions to contrast, have
contraindication to this method;
- patients with history of acute myocardial infarction, severe
hypotension, decompensated heart failure or renal
impairment have also contraindication to this method;
- pregnant women or patients who are unable to cooperate
to the breath-hold instructions are not able to have CTCA.
[47]
The method involves usage of a bolus of contrast injected
i.v., and after that realizing a coronary angiogram with
complementary ECG gating. The ACCURACY trial showed
that CTCA in comparison to ICA (invasive coronary
angiography) had similar performances in measurements
(CTCA sensitivity – 95% vs. 94%, CTCA specificity 83% vs.
83%, CTCA positive predictive value – 64% vs. 48% and CTCA
negative predictive value 99% vs. 99%) for diagnosis of CAD
with 50%/70% stenosis. [2]
Although the main issue in this non-invasive technique is
usage of radiation and scan preparation, another problem is
that presence of heavy calcification (objectively measured
by an Agatston score > 400) in case of patients with severe
CAD lowers the specificity, by creating beam hardening
artefacts and excessive image noise. [48]
Analysis of outcome data, such as in the PROMISE trial,
showed that patients with suspected CAD who did CTCA had
in long-term observation, fewer catheterizations than
patients who were functionally tested (using exercise
electrocardiography, stress echocardiography or nuclear
stress testing) although these patients hadn’t any
improvement in clinical outcome. [49], and also the SCOT-
HEART trial showed that usage of CTCA reduced fatal and
non-fatal myocardial infarction but not significantly in
patients with suspected CAD. [50]
Improving the current performance in CTCA is possible. One
48
method is measuring tthe fractional flow reserve (CTFFR).
Although it is highly time-consuming and requires computer
modeling, data shows that usage of CTFFR in CTCA is
beneficial, increasing the diagnostic accuracy in comparison
to standard CTCA. [51]
Additional usage of β-blockade and nitroglycerin before the
exam seem to increase the diagnostic performance [52] and
newer data show that CTFFR-CTCA is a safe alternative to ICA
with a significantly lower rate of ICA in comparison to
functional testing (61% cancelling rate), therefore lowering
the clinical cost and having the same clinical outcomes. [53]
Machine-learning (based on a deep learning model) in
CTFFR-CTCA seems to also make better the standard
procedure, by reclassifying patients with nonsignificant
stenosis and raising overall diagnostic accuracy (from 71% to
85%). [54]
CONCLUSION
Currently, non-invasive techniques used to diagnose stable
coronary artery disease have a very high accuracy and newer
methods seem to be comparable to the gold-standard. The
majority of the methods discussed have an optimal
performance for patients with PTP between 15-85%, and the
future of diagnosis for these patients seem to involve less
invasive measures and less radiation by improving the
current devices and by usage of machine-learning
algorithms.
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Article received on April 3, 2019 and accepted for publishing on June 23, 2019.
CLINICAL PRACTICE
Endoscopic eradication of nodular gastric vascular antral ectasia by using band ligation after argon plasma coagulation
Sandica Bucurica1,2, Mihaela Ailenei1, Mariana Jinga1,2, Florentina Ioniță Radu1,3
Abstract: Gastric antral vascular ectasia (GAVE) is an important cause of gastro-intestinal bleeding. The most common clinical presentation of GAVE is chronic occult bleeding that leads to symptomatic iron deficiency anemia, but some cases could present with acute massive bleeding. Frequently, patients are dependent by iron suplimentation, or in severe cases even blood transfusions. Endoscopic therapy is frequently necessary in acute or chronic blood loss. Over the past several years, treatment for GAVE has continued to evolve as the number of available effective therapeutic interventions has increased. These included: YAG laser, argon plasma coagulation (APC), endoscopic band ligation, cryotherapy and surgical anterectomy. Argon plasma coagulation is the most commonly used technique, but has been associated with several complications like sepsis, post-APC bleeding, gastric outlet obstruction and increased incidence of hyperplastic polyps. Endoscopic band ligation (EBL), a mechanical procedure, has been reported in the past years as an effective salvage therapy for GAVE that is refractory to other approaches, or even as the first line treatment. We present a case of nodular GAVE treated succesfully with endoscopic band ligation after unsuccesufull sessions with argon plasma coagulation.
Keywords: gastric antral vascular ectasia, endoscopic band ligation, Argon plasma coagulation, gastro-intestinal bleeding
INTRODUCTION
Gastric antral vascular ectasia (GAVE) or “watermelon
stomach” is a relatively rare cause of gastrointestinal (GI)
bleeding that mainly affects women aged 70 years and older.
The incidence is estimated to be aproximately 4% of upper
GI bleeding [1]. The term "watermelon stomach" is derived
from the characteristic endoscopic appearance of
longitudinal rows of flat, reddish stripes radiating from the
pylorus into the antrum that resemble the stripes on a
watermelon [2].
It usually presents as occult bleeding with chronic iron
deficiency anemia. Even though GAVE was first diagnosed
about six decades ago, its etiopathogenesis has not been
fully established yet, with many hypotheses proposed such
as mechanical stress, hormonal factors, and autoimmune
factors. It is associated with liver cirrhosis, autoimmune
disease, connective tissue disorders and collagen vascular
disorders (eg, systemic sclerosis, Sjogren syndrome), chronic
renal failure, bone marrow transplantation, acute myeloid
leukemia and heart disease.
Frequently GAVE patients have chronic GI bleeding, but
sometimes it can cause severe acute life-threatening
bleeding especially in elderly with multiple chronic medical
illnesses [2].
GAVE is typically located in the gastric antrum; however, it
may be also found rarely in other areas of the GI tract,
including cardia, duodenum, jejunum, and rectum. The
1 Carol Davila University Emergency Central Military Hospital, Bucharest, Romania 2 Carol Davila university of Medicine and Pharmacy, Faculty of General Medicine, Bucharest, Romania 3 Titu Maiorescu University, Bucharest, Romania
Corresponding author: Ailenei Mihaela
52
involvement of the proximal part of the stomach is very rare
and commonly located within a diaphragmatic hernia.
At endoscopy, GAVE may appear as 2 types. First type is the
diffuse punctuate lesions in the antrum typically seen in
male patients with cirrhosis and commonly accompanied by
acute bleeding. Second one is the red lesions organized in
stripes radially departing from the pylorus, known as
“watermelon stomach”, mostly common in females with
connective tissue diseases and usually present with occult
bleeding [1].
Histopathologically, GAVE is characterized by vascular
ectasia, spindle cell proliferation, and fibrohyalinosis.
Immunohistochemical staining for CD61, a platelet marker,
further confirms a diagnosis of GAVE [3].
Over the years, treatment for gastric antral vascular ectasia
(GAVE) has continued to evolve and the number of available
treatments has continued to increase, including surgical,
medical and endoscopic therapies
Medical therapy has not clearly shown satisfactory results.
Multiple drugs, such as hormonal (estrogen-progesterone)
therapy, steroids, octreotide and tranexamic acid, have been
tried to control GAVE-related bleeding. After all, no one has
clearly shown satisfactory results in order to consider
medical therapy as a valid alternative to an invasive
approach.
Endoscopic therapies have rapidly become the first line
therapy with argon plasma coagulation (APC) as the most
common used method and more recently with
radiofrequency ablation system (RFA) using Halo90 catheter
and endoscopic band ligation (EBL). Both of them have been
shown to be safe and effective for GAVE treatment. The
latter two have been utilized in treatment of severe, diffuse,
APC refractory GAVE. The clinical outcomes of ablative
therapy such as APC treatment or HALO90 system were
reported as 80%-100% success rate.
Other therapies include Nd:YAG (neodymium:yttrium-
aluminum-garnet) laser coagulation, but with a higher risk of
perforation given the deeper thermal effect. Endoscopic
sclerotherapy, heater probe, cryotherapy have also been
described in the literature. For unresponsive cases to
endoscopic therapy, surgery with antrectomy can be
considered but carries a high surgical risk, especially in the
cirrhotic patients.
APC is most commonly used method, but has been
associated with sepsis, post-APC bleeding, gastric outlet
obstruction and increased incidence of hyperplastic polyps’
formation. It is needed multiple sessions of APC to reduce
bleeding episodes and/or decrease transfusion dependence.
APC has been found to be equally effective in the treatment
of GAVE and is superior to ND:YAG laser in cost, convenience
and complication rates(4).
The non-ablative treatment options is the endoscopic band
ligation. EBL was firstly reported as the treatment for
refractory GAVE in the patients who failed other treatment
modalities such as APC or hormonal therapy by Sinha et al.
[5]
Endoscopic band ligation has been reported as an alternative
effective endoscopic therapy and the rate of complication is
low in comparison with those reported for APC in
retrospective studies [6].
A case series of 9 patients reported by Wells et al also
showed superiority of EBL over endoscopic thermal therapy,
which were APC and bipolar thermal probe therapy, for the
rate of re-bleeding, duration of hospitalization and post
procedure transfusion. The complications reported for this
procedure were very small. Band ligation was prefered as
the first line treatment regarding of the extensive
involvement of the lesion in the patients. According to the
result of the treatment mentioned above, endoscopic band
ligation could be considered as first line treatment options
for the GAVE patients especially for extensive area of
involvement. [7]
A recent prospective study showed endoscopic
improvement with the use of endoscopic band ligation in
91% of the patients, with a significant improvement in the
hemoglobin and ferritin levels. Band ligation in GAVE has
been associated with transient abdominal pain in a minority
of the patients, but no major complications have been
reported in the literature. [9]
Some studies suggest that the number of sessions required
for GAVE eradication is inferior when using EBL compared to
APC, resulting in inferior health care costs. However,
randomized controlled trials are lacking to determine
whether EBL is more cost effective than APC as the primary
endoscopic therapy for GAVE. [9, 10]
Although initial reports of these endoscopic modalities are
encouraging, well-performed, larger, prospective studies are
needed before providing any definitive conclusion.
CASE PRESENTATION
Clinical data
We present a case of a 57-year-old female, diabetic with
multiple microvascular complications – diabetic polineuro-
pathy and chronic renal disease, hypertensive, with
moderate hypochromic microcytic anaemia and a positive
Vol. CXXII • No. 2/2019 • August • Romanian Journal of Military Medicine
53
fecal occult blood test (FOBT), already in treatment with iron
therapy who presented for abdominal pain, fatigability,
phisical astenia and arthralgias. She denied no change in
weight, bowel pattern, or stool color. The physical
examination revealed paleness of the skin and mucosa and
otherwise unremarkable.
Laboratory data
Labs indicates a moderate hypochromic microcytic anaemia
(hemoglobine level – 9.4 g/dL, mean corpuscular volume –
70.2 fL, hematocrit – 31.1%, mean corpuscular hemoglobin
– 21.2 picog and sideremia – 26 microg/L.
Endoscopy
Superior digestive endoscopy showed hypertrofic gastric
antral vascular ectasia with mucosal eryhema, friability and
visible small vessels extending radially in linear rows
throughout the antrum and a duodeno-gastric reflux. She
underwent serial argon plasma coagulation treatments and
a second gastroscopy was performed next day which
showed post argon plasma coagulation ulcers which were
biopsied.
Histopathology data
Ulcer post argon plasma coagulation biopsy performed
showed modifications of chronic inactive gastritis, but GAVE
was not confirmed on biopsy.
Evolution
After two months and with iron therapy, the hemoglobin
level was normalised (12.7 g/dL) with low mean corpuscular
volume and mean corpuscular hemoglobin. At the
endoscopic examination the macroscopic appearance
persisted with multiple friable hypertrofic and nodular antral
vascular ectasia and duodeno-gastric reflux.
At 3 months follow-up, hemoglobin level mantained in the
normal interval (13.5 g/dL), but the endoscopic appearing
was worst, with larger, friable, with edema and hypertrofic
gastric atral vascular ectasia (Figure 1). We decided to apply
6 elastic bands on the biggest lesions with success (Figure 2).
No complications of the procedure were reported, and the
patient was discharged after 24h.
Figure 1: Endoscopic appearance from the index endoscopy, demonstrating multiple erythematous friable antral hypertrophic and
nodular lesions, representing nodular gastric antral vascular ectasia (GAVE)
Figure 2: Endoscopic image from the band ligation of GAVE
Two months later, hemoglobin level was stable (13.4g/dL).
The upper endoscopy revelead small hyperemic antral
circumferential disposed lesions with no signs of bleeding
and no hypertrophy, with almost complete eradication of
GAVE (Figure 3).
DISCUSSION
GAVE is a poorly understood entity, of unknown etiology,
and an increasingly identifiable cause of chronic iron
deficiency anemia. The pharmacological management of
54
GAVE had only poor results, so the mainstay of GAVE
management remains endoscopic therapy.
Figure 3. Endoscopic appearance 2 months after endoscopic band
ligation
Figure 4. Suggested flow chart for treatment algorithm [14].
GAVE: Gastric antral vascular ectasia; APC: Argon plasma
coagulation; RFA: Radiofrequency ablation; EBL: Endoscopic band
ligation.
APC is a modality of non-contact electrocoagulation that
applies high-frequency energy into tissue to cause thermal
effects, which has been used successfully to treat GAVE with
an effective transient response, but primary failure rates of
therapy of up to 14% have been reported. Some authors
suggest that this endoscopic method is insufficient in order
to achieve medium and long-term treatment success, as it
has been associated with a high recurrence rate (40–100%)
[11].
In addition, APC might have complications, such as sepsis,
pyloric stenosis and gastric outlet obstruction syndrome, in
20–33% of the patients [12].
EBL has been reported to be a relatively easy technique for
GAVE therapy, has been shown to be safe and effective with
lower complication rates in comparison with APC. Both Sato
et al. [6] in 2012 and Prachayakul er al. [13] in 2013 conclude
that EBL may be useful in the treatment of GAVE, to avoid
the high recurrence rate after APC.
In this case, the patient was initially treated with APC after
being diagnosed with GAVE as the cause of iron deficiency
anemia, but this strategy was not successful. APC treatment
might not be effective in some cases, especially in the case
of hypertrofic and nodular type of GAVE, and this could be
explained by the limited depth of thermal injury.
Since the histological changes are present in the mucosa and
submucosal layer, EBL may be more effective for GAVE
because of its ability to obliterate the submucosal vascular
plexus like for esophageal varices. In this patient, the
presence of extensive areas of the antrum affected with a
high-density of both mucosal and submucosal vascular
malformations is a likely explanation for the primary failure
of the APC treatment.
It is becoming apparent that patients with severe, diffuse or
refractory disease require multimodal therapy. Our case not
only shows that, but also that patients specifically with
nodular variant GAVE require and respond well to
multimodal therapy.
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argon plasma coagulation for gastric antral vascular ectasia
associated with liver diseases. Dig Endosc 2012; 24: 237-242
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7. Wells CD, Harrison ME, Gurudu SR, Crowell MD, Byrne TJ,
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56
Article received on May 28, 2019 and accepted for publishing on June 23, 2019.
CLINICAL PRACTICE
Death due to a rare posttraumatic complication: fat embolism
Cristina Podilă1, Mihaela C. Șomlea2, Bogdan A. Buhaș3, Adrian S. Judea4, Andreea A. Hleșcu5, Nicolae Nicoară4, Flavia Săndoiu1, Paula Marian6, Bianca Hanganu5, Irina S. Manoilescu5,7
Abstract: Fat embolism is a rare complication of high or medium intensity trauma. It is caused by the formation of fat particles in the territories of small terminal circulation, especially at pulmonary, tegumentary and cerebral levels. The mechanism underlying the fat embolism is described by several different theories in literature. In legal medicine, fat embolism raises many controversies upon the diagnostic certainty of the thanatogenerator mechanism leading to death. The occurrence of fat embolism syndrome followed by death must be properly explained so that the fatality can be adequately framed from a legal point of view. In this paper the authors present three cases in which victims of trauma died due to clinically undiagnosed fat embolism, the diagnosis being established only by postmortem histopathological examination. The authors underline the fact that the diagnosis of fat embolism syndrome, although it is a clinical one, it is often established only during autopsy.
Keywords: fat embolism, trauma, death, autopsy, diagnosis
INTRODUCTION
Embolism represents the motion through circulatory blood
flow of a material which is not present in blood in normal
conditions and its subsequent lodging inside the blood
vessels. In the case of fat embolism, the material carried
through the blood is represented by fat particles that reach
the level of microcirculation. Fat embolism syndrome
represents the systemic manifestation of the fat particles
being present inside the microcirculation.
Fat embolism was first described by Zenker in 1862 in the
case of a railroad worker who died of crushing injuries. In
1873 Bergmann diagnosed fat embolism in a living patient
who had suffered a fracture of the femoral bone [1, 2].
The causes of fat emboli formation are multiple, both
traumatic and non-traumatic. The most frequent traumatic
causes are: long bone fractures, orthopedic procedures, soft
tissue trauma (fat tissue laceration), liposuction and
mastectomy, neurosurgical interventions. Non-traumatic
causes include: acute pancreatitis, extensive burns,
diabetes, fatty liver due to diets rich in extrinsic fats and oils
[2, 3]. Exceptionally, fat embolism has been observed in
cases of hepatic steatosis (in alcoholics and diabetic patients
with hepatic damage) due to the destruction of hepatocytes
and subsequent release of fat particles [4, 5].
1 Bihor County Forensic Service, Oradea, Bihor, Romania 2 County Clinical Emergency Hospital Cluj-Napoca, Clinical Department of Dermatovenerology 3 County Emergency Hospital of Oradea, Department of Urology, Oradea, Romania 4 University of Oradea, Faculty of Medicine and Pharmacy, Department of Morphological Disciplines, Oradea, Romania 5 Grigore T. Popa University of Medicine and Pharmacy of Iasi, Romania, Department of Legal Medicine 6 University of Oradea, Faculty of Medicine and Pharmacy, Department of Medical Disciplines 7 Institute of Legal Medicine of Iași, Romania
Corresponding author: Andreea A. Hleșcu
Vol. CXXII • No. 2/2019 • August • Romanian Journal of Military Medicine
57
Fat embolism occurs in 90% of patients who have suffered a
trauma, but only 2-5% of them develop the fat embolism
syndrome; particularly at risk are those with fractures of the
long bones. It is difficult to estimate the duration of this
syndrome because the symptoms are often subacute or
masked by other symptoms of trauma [2, 3].
Post-mortem studies have shown a different but a very high
incidence of fat embolism. Thus, a study by Behn C. et al. on
527 autopsies demonstrated the presence of fat embolism
in 92 of these [6]. Another study conducted by Hiss et al. in
1996, on 53 victims of aggression followed by death, showed
a high incidence of fat embolism. All the subjects studied
were young, male, victims of aggressions, suffering severe
trauma 24 hours before death. In thirty two cases the
presence of fat embolism was observed in the main organs,
with no other obvious cause of death. The authors of the
study hypothesized that the source of fat embolism was the
mechanical disintegration of the subcutaneous adipose
tissue [7].
In cases of fat embolism there is a poor correlation between
post-mortem and clinical findings. This discrepancy
ultimately gave rise to the concept of "iceberg effect of fat
embolism" [8- 12]. This justifies, as well as cases with a
insufficiently outlined clinical picture for a particular
pathology, or a clinical picture that cannot explain the
occurrence of death, the importance of forensic autopsy and
postmortem laboratory investigations (histopathological
and toxicological) in order to establish the thanatogenerator
mechanism and the causal link between trauma / illness and
death, and ultimately the legal nature of the case, i.e.
suicide, accident or homicide [13- 19].
MATERIALS AND METHODS
We present three cases of trauma in which the cause of
death was the fat embolism syndrome. All the cases are
characterized by a rapid clinical deterioration leading to
death, so that a clinical diagnosis of fat embolism syndrome
could not be established antemortem.
Case no. 1
Male, 72 years old, chronic alcohol consumer, with past
medical history of left femoral fracture and right sided
craniotomy, is admitted to hospital for head trauma. At the
time of admission physical examination revealed multiple
ecchymoses, pain at the pelvic level, lower limbs and
abdomen. Clinical and paraclinical investigations established
the following diagnosis: minor craniocerebral trauma, facial
trauma, posttraumatic subarachnoid hemorrhage, dura
mater hygroma, abdominal contusion, pelvic contusion.
Surgical intervention was performed to evacuate the dura
mater hygroma 6 days after the admission. Evolution was
initially favorable. On the 4th postoperative day, the patient
developed a febrile syndrome. Laboratory analysis
highlighted: elevated leucocyte count (13.390 of which
11.270 neutrofils); elevated serum amylase (225 U/L);
lowered erythrocyte count (3.83 milion); hematocrit levels
as low as 40.08 %; low thrombocytes count (137.700);
increased level of the liver enzyme AST to 48 U/L; low
creatinine serum levels (0.69 mg/dl) and reduced glomerular
filtration rate to 85 mil/min/1.73 m2. The next day the
patient suffered cardiorespiratory arrest that did not
respond to resuscitation maneuvers, followed by death. The
forensic autopsy was performed. The external examination
of the body showed: multiple injuries denoting violence such
as ecchymoses and abrasions; signs of medical treatment at
the level of the skull, i.e. recent surgical incision and an old
whitish scar. The internal examination showed: on the head,
2 craniotomy areas, one of them being recent, subarachnoid
hemorrhage, areas of flaccid cerebral structure, small
petechial hemorrhagic areas disseminated throughout the
brain. The examination of the lungs showed: pulmonary
stasis and edema, and areas of pulmonary condensation.
Fragments of brain and lungs were harvested during autopsy
and subsequently examined by optic microscopy using the
Sudan III staining. The microscopic examination revealed fat
emboli in the brain and lungs. Following the postmortem
macroscopic and microscopic examination we established
that the cause of death was the fat embolism syndrome.
Case no. 2
Male, 54 years old, was admitted to the hospital with the
diagnosis of: head trauma (subarachnoid hemorrhage,
fracture of the left temporal bone with extension to the
mastoid bone), face trauma (fracture of right jaw,
comminuted fracture of the nose) and chest trauma (left
pneumothorax, multiple rib fractures).
The patient was hospitalized for 35 days, during which
multiple pleurotomies and bronchoscopies were performed.
Laboratory examinations showed: increased leucocyte count
(25.170 of which 21.100 neutrofils); low red blood cell count
(2.612 milions); low hematocrit (21.240 %); low hemoglobin
level (7.793 g/dl); normal thrombocyte count; increased
level of AST (103 U/L); increased serum creatinine (4.28
mg/dl); increased GGT levels (93 U/L) and reduced
glomerular filtration rate (10.8 mil/min/1.73 m2). Clinical
evolution was initially favorable. On day 34 after admission
the patient developed a feverish syndrome. The next day he
suddenly suffered cardiorespiratory arrest, followed by
death. A forensic autopsy was performed. The external
examination of the cadaver revealed bruises and signs of
58
recent medical treatment. The internal examination
showed: linear head fracture, subdural hematoma under
partial resorption, small petechial hemorrhagic areas in the
brain, pulmonary edema, and areas of pulmonary
condensation. Fragments of organs were harvested (brain,
lung) and examined by optic microscopy using Sudan III
staining. Following the macroscopic and microscopic
examinations we concluded that the cause of death was the
fat embolism syndrome.
Case no. 3
Male, 20 years old, victim of a traffic accident, was admitted
to the hospital with the diagnosis of: polytrauma due to road
traffic accident, major craniocerebral trauma with diffused
cerebral edema, multiple rib fractures, fracture of the left
iliac wing and left ischial bones, fracture of the left femoral
neck, and type III A fracture of the femoral diafisis. Patient
was admitted in the hospital for 7 days and underwent a
surgical intervention for the femoral fracture. During the
first days after the surgery the patient was hemodynamically
stable. On day 4 the patient showed tachypnea, tachycardia,
and fever and his clinical condition suddenly worsen. The
laboratory examinations showed: low leucocyte count (1.56
of which 1.37 neutrofils); reduced numbers of erythrocytes
(2.31 milions); low hematocrit (23.3%); low hemoglobin
(6.77 g/dl); reduced number of thrombocytes (58.600/
mmc); increase in liver enzyme AST (272 U/L) and ALT (250
U/L); increased serum creatinine (2.43 mg/dl); increased
serum urea (94.16 mg/dl) and reduction of glomerular
filtration rate to 27.21 mil/min/1.73 m2. Death occurred on
the same day. At autopsy, the external examination of the
corpse revealed: multiple ecchymoses, abrasions,
hematomas, signs of medical treatment. The internal
examination showed: brain contusion; multiple rib fractures;
pulmonary edema, pulmonary condensation areas,
pulmonary infarction; fractures of the pelvis and of the left
femor. The microscopic examination of the fragments of
brain and lungs collected during the autopsy and stained
with Sudan III showed fat embolism. Therefore, based on
macroscopic autopsy findings and histo-pathological
examination of the brain and lung fragments, we established
that the cause of death was the fat embolism syndrome.
RESULTS
In all the three cases the victims suffered various trauma: in
the first case the victim suffered soft tissues and head
injuries, in the second case the victim suffered a polytrauma
with multiple fractures and soft tissue injuries and in the
third case the victim suffered craniocerebral trauma, soft
tissue injuries and long bone fractures. Therefore, in all the
cases, the etiological conditions for the fat embolism
occurrence were met. However, in none of the cases the
diagnosis was clinically established antemortem. The
examination by optic microscopy of the fragments of brain
and lungs collected during autopsy and stained with Sudan
III showed in all the cases the fat microemboli in the form of
orange globes disseminated throughout the fields examined
microscopically (figures 1-4) and allowed the postmortem
diagnosis of fat embolism. Therefore, in all three cases
presented, the results of the histopathological examination
of the fragments harvested from the brain and the lungs
during the autopsy were essential for determining the cause
of death.
Figure 1: Microscopic aspect of brain tissue
Sudan III stain x 40 (ice exam)
Figure 2: Microscopic aspect of lung tissue
Sudan III stain x 20 (ice exam)
Figure 3: Microscopic aspect of lung tissue
Sudan III stain x 40 (ice exam)
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59
Figure 4: Microscopic aspect of lung tissue
Sudan III stain x 10 (ice exam)
DISCUSSION
Fat embolism occurs due to the mobilization of fat cells or
fat released by them, followed by their direct penetration
into open blood vessels or lymphatic channels. Most emboli
have a diameter of 15 to 40 μ; the fat emboli in the lungs are
generally larger than those in the large arteries of the
systemic circulation [11].
Several theories are mentioned in the literature to explain
the pathogenesis of the fat embolism [20].
The mechanical theory shows that mobilization of fat
particles occurs due to trauma to the bones or soft tissues.
As a consequence, the fat particles released by the trauma
enter the venous circulation from where they reach the
lungs, where the majority remains, but some of them can
also pass into the systemic circulation, reaching other
organs.
The biochemical theory, also known as the emulsion
instability theory, is mostly useful in explaining the non
traumatic fat embolism.
The intravascular coagulation theory holds that in stressing
conditions, substances that activate disseminated intra-
vascular coagulation and aggregation of fat particles are
released.
The toxic trauma theory claims that small blood vessels are
affected by high concentrations of fatty acids in the plasma
leading to increased vascular permeability.
The mechanical theory is based on the concept of the
mobilization of fatty bone marrow from the long bones
diaphysis. In the cases presented by us, only one patient
suffered a recent fracture of the femur. In the other two
cases we have to consider the trauma of soft tissues
(hypodermic tissue) as the cause of the fat embolism, by
noting that in both cases multiple ecchymoses were
observed on the skin.
From a clinical point of view, Gurd and Wilson have
developed the major and minor criteria which allow which
allow for the diagnosis of fat embolism. The major criteria
are: axillary or subconjunctival petechiae; hypoxaemia
(PaO2 <60 mm Hg, FIO2 = 0); central nervous system
depression disproportionate to hypoxaemia; pulmonary
oedema; radiological signs and symptoms of respiratory
insufficiency; cerebral changes unrelated to a cranial trauma
or other illness; rash. The minor criteria are: tachycardia
more than 110 bpm; pyrexia more than 38.5°C; fat globules
present in urine; changes in renal function (reduced urine
output); drop in haemoglobin level (more than 20% of the
value upon admission); drop in haematocrit values; drop in
platelet values (more than 50% of the value upon
admission); increased erythrocyte sedimentation rate
(greater than 71 mm per hour); fat globules present in the
sputum; emboli present in the retina; tachicardia; fever;
renal insufficiency; sudden thrombocytopenia. According to
Gurd and Wilson the diagnosis of fat embolism can be
established if either one major criterion and 4 minor criteria
or 2 major criteria are met [21].
Lindeque suggested that the criteria of Gurd and Wilson may
under-diagnose the syndrome, and proposed the following
criteria based on respiratory parameters: Pao2 kPa of less
than 8Fio2 0.21; Paco2 kPa or pH of less than 7.3 or more
than 7.3; respiratory rate greater than 35 breaths/min−1
even after adequate sedation; increased breathing efforts
showed by: dyspnea, use of accessory muscles, tachycardia
and anxiety [22]. Any patient with a fractured femur and/or
tibia, presenting one or more of these criteria, was
diagnosed with fat embolism syndrome. These criteria led to
the diagnosis of fat embolism syndrome in 29% of patients
in a series of 55, which is higher than other series, especially
since this study excludes patients with thoracic lesions,
where some of Lindeque's clinical signs may appear in the
absence of fat embolism [22].
Petechial eruption is considered a pathognomonic clinical
sign for fat embolism syndrome. It may occur in about 60%
of patients, usually on the conjunctiva, on the oral mucous
membrane and on the skin of the neck and shoulders. This
distribution can be explained by the drops of fat that
accumulate in the aortic arch before the independent
embolization at skin level through the subclavian and carotid
vessels [20, 23-25]. The factors contributing to the petechial
eruption are: stagnation of blood, loss of coagulation factors
and platelets, and damage to the endothelial walls due to
free fatty acids (FFA) leading to rupture of capillaries [25].
In the vast majority of cases, the fat embolism remains
asymptomatic, and the fat emboli are dispersed into small
cells and phagocyted by macrophages or embedded in
60
hepatic cells [26, 27]. Thus, many cases remain undiagnosed
before death.
In the three cases presented, the symptomatology before
death was poor and unspecific (febrile syndrome,
tachycardia, tachypnea), and remained undiagnosed. The
diagnosis of fat embolism syndrome was established only
after performing the autopsy, and the histopathological
examination of the brain and lung fragments stained
specifically with Sudan III. Therefore, for post mortem
diagnosis of fat embolism syndrome, it is essential to
perform a histopathological examination with special stains
that highlight the presence of fat emboli in the tissues and
organs.
In the cases presented in this paper, fat embolism at the
pulmonary and cerebral level was observed. According to
literature, brain and lung localizations are the most
important, although in most cases pulmonary fat embolism
remains clinically asymptomatic. In order to be able to certify
fat embolism as the cause of death, it is necessary for
histopathological examinations to find fat emboli on a large
part of the examination fields. The gravity of the
consequences of pulmonary embolism also depends on the
size and amount of fat emboli, as well as whether or not they
pass into the systemic circulation to the lung.
In the brain, emboli produce small petechial hemorrhages,
areas of ischemic necrosis and hemorrhage or necrosis and
demyelination. Cerebral embolism is considered in literature
as a paradoxical event, because it requires the presence of
cardiac atrial septal defects in order to be explained. In the
presented cases, there was no autopsy finding that showed
neither atrial or ventricular septal defects nor patent arterial
canal that could explain the cerebral fat embolism. An
explanation of the pathophysiological mechanism which
determined the cerebral embolism could not be found in this
study.
The cause of death in all the three cases presented in this
paper was the fat embolism. The diagnosis was established
with certainty only after autopsy, by a histopathological
examination which revealed the presence of fat emboli in
the lung and brain tissues. Of the cases presented only one
suffered a recent fracture of the femur; another presented
in addition to trauma paraclinical changes suggestive of
acute pancreatitis as a contributing factor; none had cardiac
malformations that could explain the paradoxical fat
embolism in the brain; all of the cases showed multiple
lesions of the subcutaneous tissue and death occurred
shortly after the initial trauma or after surgical interventions.
Death due to fat embolism can fall into the category of
violent or non-violent deaths. Regardless of the cause of fat
embolism, from forensic point of view the fat embolism is
considered a complication that leads to a secondary causal
relationship; in other words between the trauma/ initial
pathology and death an intermediate link is inserted
represented by a complication (the fat embolism) which is
connected to a greater or lesser extent to the initial trauma/
pathology [28-30].
CONCLUSION
From forensic point of view, the diagnostic certainty in
posttraumatic lesions is a priority objective. From the
diagnosis it is possible to reconstruct the thanatogenerator
mechanism and finally it can be useful to respond to the legal
aspects of the case, i.e. the causal relationship between
trauma and death.
In the case of trauma with reduced thanatogenerator
potential, which usually evolve without complications, the
occurrence of fat embolism syndrome followed by death
must be appropriately explained so that the case can be
properly framed from a legal point of view. It is important to
emphasize that the histopathological examination using
specific stainings, such as Sudan III, has a fundamental and
incontestable role in the diagnosis of fat embolism and in
estimating its gravity, and therefore, its implication in the
occurence of death.
Conflict of interest: The authors declare that there is no conflict of
interest.
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5. Popa AR, Vesa CM, Uivarosan D, Jurca CM, Isvoranu G, Socea B,
Stanescu AM, Iancu MA, Scarneciu I, Zaha DC. Cross Sectional Study
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Regarding the Association between Sweetened Beverages Intake,
Fast-food Products, Body Mass Index, Fasting Blood Glucose and
Blood Pressure in the Young Adults from North-western Romania.
Rev Chim-Bucharest. 2019; 70(1):156-160.
6. Behn C, Höpker WW, Püschel K. Fat embolism-a too
infrequently determined pathoanatomic diagnosis.
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Trauma Acute Care Surg. 1996; 40(1):27-30.
8. Ioan B, Alexa T, Alexa ID. Do we still need the autopsy? Clinical
diagnosis versus autopsy diagnosis. Rom J Leg Med. 2012; 20(4):307-
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9. Roman G, Bala C, Creteanu G, Graur M, Morosanu M, Popa AR,
Pircalaboiu, L, Radulian G, Timar R, Cadariu AA. Obesity and health-
related lifestyle factors in the general population in Romania: a cross
sectional study. Acta Endo (Buc). 2015; 11(1):64-71.
10. Juncar M, Popa AR, Baciut MF, Juncar RI, Onisor-Gligor F, Bran
S, Baciut G. Evolution assessment of head and neck infections in
diabetic patients - A case control study. J Craniomaxillofac Surg.
2014; 42(5):498-502.
11. Chan KM, Tham KT, Chiu HS, Chow YN, Leung PC. Post-traumatic
fat embolism-its clinical and subclinical presentations. J Trauma.
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12. Velnic AA, Hanganu B, Petre-Ciudin V, Ioan BG. Clinical diagnosis
versus autopsy diagnosis in head trauma. Forensic Science
International. 2017; 277 (Suppl. 1): 209
13. Judea-Pusta CT, Muțiu G, Pașcalău AV, Buhaș CL, Ciursaș AN,
Nistor-Cseppento CD, Bodea A, Judea AS, Vicaș RM, Dobjanschi L,
Pop OL. The importance of the histopathological examination in
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14. Pusta CT, Mihalache G, Buhas C, Pop O. A rare case of cardiac
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Article received on May 13, 2019 and accepted for publishing on June 23, 2019.
CLINICAL PRACTICE
Papillary thyroid carcinoma arising on a hypertrofic pyramidal lobe
Rodica Petris1, Ionut B. Sandu1, Adina Dragomir1, Dumitru Ioachim1, Cristina Iosif2, Ruxandra Dănciulescu-Miulescu3, Alexandra Mirica3, Diana Paun3
INTRODUCTION
Development of thyroid gland starts by the pharyngeal
epithelium thickening floor which later forms a diverticulum
which, in its development is pushed caudally. The descent
path is usually anterior to hyoid bone but it can also be
posterior or through the hyoid bone and ends on the
anterior surface of the first few tracheal rings.
This primitive steam that connects primordium with
pharyngeal floor becomes thyroglossal duct. Until the
second month of gestation thyroglossal duct devolve,
leaving at its place a small lump – the foramen cecum, at the
unification of third medium with posterior third of the
tongue, but portions of the duct associated with thyroid
tissue can persist at any site between tongue and thyroid [1,
2].
Cells in the lowest portion of the thyroglossal duct which
comprises normal thyroid tissue differentiates in forming
pyramidal lobe of the thyroid gland. Pyramidal lobe often
comes out from the thyroid isthmus, but can also come from
the medial side of one or both thyroid lobes [1]. The
pyramidal lobe is thought to be present in 15-75% of the
general population [1, 3]. Thyroglossal duct fails to involute
in approximately 7% of the population [4].
Many remnants of thyroglossal duct are never detected
clinically (2) and malignant transformation is uncommon [5].
CASE REPORT
We present the case of a 50 years old female patient with
chronic renal failure of unknown etiology (probably
secondary to hyper blood pressure), with Graves Disease (in
treatment with antithyroid drugs for about 1 year) who was
admitted in our department after she has initially presented
in an ENT department (Otolaryngology) for the investigation
of a tumoral mass located in the midline upper neck. At that
moment physical exam revealed a 2/3 cm mass between the
hyoid bone and the thyroid cartilage, mobile on swallowing,
painless spontaneously and on palpation, covered by normal
skin. IRM exam revealed a bilobate lesion 2.9/1.1 cm, very
well encountered, in close relationship with the adjacent
muscles and the hyoid bone, without any other pathological
changes on the structures of the anterior neck: no enlarged
lymph nodes. There were no reference about thyroid gland
on the IRM report. The IRM conclusion was: expansive
anterior cervical soft tissues tumoral mass. Surgical excision
of the tumoral mass and simultaneous removal of the central
portion of the hyoid bone (Sistrunk procedure) was
performed and the pathology report showed papillary
thyroid carcinoma arising from thyroglossal duct. In our
department, three months later, thyroid ultrasound showed
hypoechoic, inhomogeneous echotexture suggestive for
chronic autoimmune process, hypoechoic nodule with
discrete Doppler flow, without hypoechoic halo located at
the connection of the right thyroid lobe with isthmus and
two micro lymph nodes with intense Doppler flow, without
hilum of 0.5/0.4 cm and 0.7/0.4 cm located anterior of the
larynx. Tumoral mass previously removed in the ENT
department was reviewed and the pathology report showed
tumoral multilobulated pyramidal thyroid lobe with pattern
1 C.I. Parhon National Institute of Endocrinology, Bucharest, Romania 2 St Maria General Hospital, Bucharest, Romania 3 Carol Davila University of Medicine and Pharmacy, Bucharest, Romania
Vol. CXXII • No. 2/2019 • August • Romanian Journal of Military Medicine
63
of solid and sclerosant variant of papillary carcinoma,
infiltrative into fibro conjunctive, adipose and muscular
adjacent tissue (Figure 1 and Figure 2) and areas of micro
angioinvasion of the capsule (Figure 3).
Figure 1: Papillary carcinoma infiltrative into fibroconjunctive,
adipos and muscular adjacent tissue (x20 HE)
Figure 2: Papillary carcinoma infiltrative into fibroconjunctive
adipose and muscular adjacent tissue (x40 HE)
Figure 3: Micro invasion of the capsule (x200 HE)
In this context, we decided total thyroidectomy (also as a
treatment for Graves Disease) with dissection of central
lymph nodes compartment. Histopathology report revealed
embedded thyroid isthmus focus of papillary thyroid
carcinoma 0.7/0.6 cm with tumoral pattern similar to that of
tumoral pyramidal lobe previously removed (Figure 4), with
areas of marginal invasion of the capsule (Figure 5) and
micro angioinvasion of the capsule (Figure 6). The pathology
report also showed reactive lymphadenopathy and post
surgery staging was pT3N0.
Figure 4: Embedded thyroid isthmus focus of papillary thyroid
carcinoma (x20 HE)
Figure 5: Marginal invasion of the capsule (x100 HE)
Figure 6: Microangioinvasion of the capsule (x100 HE)
Radioactive iodine therapy was decided. Postsurgery,
thyroglobulin level after Levothyroxine withdrawal is 0.2
ng/ml with unmeasurable thyroglobulin antibodies and 50
mCi 131I was administered. Post ablation thyroid scan
showed no uptake of 131I in the thyroid bed or elsewhere in
the body. Because of the association of BRAF mutation with
papillary carcinoma of the pyramidal thyroid lobe, genetic
testing of BRAF gene were performed and they were
negative for somatic mutations in the 600 codon.
DISCUSSION
The detection of a pyramidal lobe or a thyroglossal duct in
patients with hyperthyroidism is indicative of autoimmune
64
hyperthyroidism. The vestiges of thyroglossal tract are more
often seen in patients with Graves Disease compared with
patients with autonomously functioning thyroid nodules and
this is related with the presence of stimulating thyrotropin
receptor antibodies [6, 7]. Pyramidal lobe can be the primary
or secondary site of thyroid malignancy and during
thyroidectomy, total excision of the pyramidal lobe is
essential for patients with thyroid cancers who undergo
radioactive iodine treatment (RAI) because the presence of
pyramidal lobe prevents the increase in TSH and absorbs a
large amount of the isotope and thus decrease the possibility
to benefit from the treatment [8-10]. Residual pyramidal
lobe can harbor cancer cells and from this point of view its
total excision is indicated in thyroid cancers. In case of
probable recurrence of malignant diseases due to pyramidal
remnants, scintigraphy, ultrasound of the neck, computed
tomography are indicated [11-13]
Thyroid pyramidal lobe can be the origin or recurrent site of
papillary thyroid carcinoma. Malignant tumors arising from
pyramidal lobe are rare and are associated with a high rate
of concurrent thyroid cancer and it must be differentiated
from thyroglossal papillary cancers because pyramidal
cancer requires orthostatic thyroid surgery which is not
always necessary in papillary thyroglossal cancers [14, 15].
Pyramidal lobe tumors are associated with poor prognostic
factors such as: extra thyroidal extension, advanced T-stage,
cervical lymph node metastasis, advanced AJCC stage (III, IV),
BRAF mutation, multifocal thyroid cancer [16, 17]. In our
patient there was one single embedded thyroid focus, no
local lymph nodes metastasis and no distant metastasis.
BRAF mutation was negative.
Malignant tumors arising from thyroglossal duct are also
rare [18]. The majority are papillary carcinomas (about 94%)
and less than 5% are squamous carcinoma [19]. The Sistrunk
procedure that implies the simultaneous removal of the
central portion of the hyoid bone to ensure the complete
removal of the thyroglossal tract is enough for thyroglossal
squamous carcinoma although they have a poor prognosis
and a mortality rate of 30-40% [20]. On the other hand,
papillary thyroglossal carcinomas are multicentric and
multifocal and total thyroidectomy followed by 131I ablation
and thyroid-stimulating hormone suppression is often
required. There are still controversy regarding the need for
total thyroidectomy, central or lateral compartment neck
dissection and I131 ablation therapy in cases of papillary
carcinoma of thyroglossal duct [21]. The decision depends
on: tumor size (tumors larger than 1 cm require total
thyroidectomy), abnormal findings of thyroid (multinodular
goiter, cold nodule in a thyroid iodine uptake), histopa-
thological findings, and the presence of enlarged lymph
nodes or a history of neck irradiation [22].
In conclusion: in this report we have described a papillary
thyroid carcinoma arising from a multilobulated pyramidal
lobe including from a nodular peri-isthmic remnant of the
pyramidal lobe (secondary to incompletely resected anterior
tumor of the isthmus), in a patient with Graves Disease. The
rest of the thyroid parenchyma is non tumoral. The complete
resection of the thyroid is necessary because of tumor
aggressiveness and the necessity of radioiodine ablation
therapy.
References:
1. Braun, E.M., et al., The pyramidal lobe: clinical anatomy and its
importance in thyroid surgery. Surg Radiol Anat, 2007. 29(1): p. 21-
27.
2. Allard, R.H., The thyroglossal cyst. Head Neck Surg, 1982. 5(2):
p. 134-146.
3. Geraci, G., et al., The importance of pyramidal lobe in thyroid
surgery. G Chir, 2008. 29(11-12): p. 479-482.
4. Ellis, P.D. and A.W. van Nostrand, The applied anatomy of
thyroglossal tract remnants. Laryngoscope, 1977. 87(5 Pt 1): p. 765-
770.
5. Heshmati, H.M., et al., Thyroglossal duct carcinoma: report of
12 cases. Mayo Clin Proc, 1997. 72(4): p. 315-319.
6. Kallee, R.W.U.M.E., Hyperthyroidism with or without pyramidal
lobe: Graves‘ disease or Disseminated Autonomously Functioning
Thyroid Tissue? Clinical Nuclear Medicine, 1997. 22(7): p. 451-458.
7. Cigrovski-Berkovic, M., D. Solter, and M. Solter, Why does the
patient with Graves' disease remain euthyroid/mildly hyperthyroid
following total thyroidectomy--the role of thyrotropin receptor
antibodies (TRAb) and vestigial remnants of the thyroglossal tract.
Acta Clin Croat, 2008. 47(3): p. 171-174.
8. Attie, J.N., et al., Feasibility of total thyroidectomy in the
treatment of thyroid carcinoma: postoperative radioactive iodine
evaluation of 140 cases. Am J Surg, 1979. 138(4): p. 555-560.
9. Zeuren, R., et al., RAI thyroid bed uptake after total
thyroidectomy: A novel SPECT-CT anatomic classification system.
Laryngoscope, 2015. 125(10): p. 2417-2424.
10. Pacini, F., et al., Post-surgical use of radioiodine (131I) in
patients with papillary and follicular thyroid cancer and the issue of
remnant ablation: a consensus report. Eur J Endocrinol, 2005.
153(5): p. 651-659.
11. Ryu, J.H., D.W. Kim, and T. Kang, Pre-operative detection of
thyroid pyramidal lobes by ultrasound and computed tomography.
Ultrasound Med Biol, 2014. 40(7): p. 1442-1446.
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12. Cengiz, A., H. Saki, and Y. Yurekli, Scintigraphic evaluation of
thyroid pyramidal lobe. Mol Imaging Radionucl Ther, 2013. 22(2): p.
32-35.
13. Zivic, R., et al., Surgical anatomy of the pyramidal lobe and its
significance in thyroid surgery. S Afr J Surg, 2011. 49(3): p. 110, 112,
114 passim.
14. Machens, A., H.J. Holzhausen, and H. Dralle, The prognostic
value of primary tumor size in papillary and follicular thyroid
carcinoma. Cancer, 2005. 103(11): p. 2269-2273.
15. Witt, R.L., Initial surgical management of thyroid cancer. Surg
Oncol Clin N Am, 2008. 17(1): p. 71-91, viii.
16. Ogawa, C., et al., Follicular carcinoma arising from the pyramidal
lobe of the thyroid. J Nippon Med Sch, 2009. 76(3): p. 169-172.
17. Lee, Y.S., et al., Recurrence of papillary thyroid carcinoma in a
remnant pyramidal lobe. ANZ J Surg, 2011. 81(4): p. 304.
18. Weiss, S.D. and C.C. Orlich, Primary papillary carcinoma of a
thyroglossal duct cyst: report of a case and literature review. Br J
Surg, 1991. 78(1): p. 87-89.
19. Wexler, M.J., Surgical management of thyroglossal duct
carcinoma: is an aggressive approach justified? Can J Surg, 1996.
39(4): p. 263-264.
20. Boswell, W.C., et al., Thyroglossal duct carcinoma. Am Surg,
1994. 60(9): p. 650-655.
21. Dedivitis, R.A. and A.V. Guimaraes, Papillary thyroid carcinoma
in thyroglossal duct cyst. Int Surg, 2000. 85(3): p. 198-201.
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duct cyst. Hell J Nucl Med, 2006. 9(1): p. 39-40.
66
Article received on March 11, 2019 and accepted for publishing on May 13, 2019.
CLINICAL PRACTICE
Atypical Cogan syndrome; case report
Gabriela C. Musat1,2, Roxana E. Decusara2, Ovidiu Musat3
Abstract: Cogan syndrome is a rare disease characterized by the concomitance of non-syphilitic interstitial keratitis with Meniere-like vestibulo-auditory symptoms. There are criteria for the diagnosis of both typical and atypical Cogan syndrome. We present the case of a 40 years old woman with sudden onset of hearing loss, tinnitus, intense vertigo, instability associated with kerato-conjunctivitis. The concomitance of the symptoms, the onset, and the evolution under treatment are consistent with the diagnosis of atypical Cogan syndrome.
Keywords: Cogan syndrome, atypical Cogan syndrome; vertigo; hearing loss
INTRODUCTION
Cogan syndrome is a disorder characterized by the
association between the Meniere-like vestibulo-auditory
symptoms and ocular symptoms (interstitial keratitis).
Although the first to describe a disorder associating ocular
and inner ear symptoms were Morgan RF, Baumgartner in
1934 [1], the name of the disease comes from Dr. David
Cogan who published in 1945 a series of 4 cases of patients
with non syphilitic interstitial keratitis and vestibulo-
auditory symptoms [2]. In 1980 Haynes et al proposed the
enlargement of the criteria for the diagnosis, defining typical
and atypical Cogan syndrome. They proposed that other
ophthalmologic inflammatory manifestations such as
episcleritis, uveitis, conjunctivitis, can be considered as
disease criteria for atypical syndrome. [3]
For a disease described such a long time ago there is very
little knowledge about the etiology of the disorder. Until
now, approximately 250 cases have been published but we
still don’t understand the etiopathogeny of the disease. It is
considered an autoimmune disorder. This disease seems to
affect young Caucasian adults with ages ranging between 25
to 35 years old, in most of the cases. [5]
CLINICAL FEATURES
Ocular manifestations: The main characteristic of the
disease is the ocular involvement. Usually patients have red
eye, eye pain and photophobia. The typical Cogan syndrome
is defined by the presence of the non syphilitic interstitial
keratitis. The examiner might notice granular and irregular
infiltrate on the posterior part of the cornea.
Neovascularization is also a possibility. Blindness and
amaurisis can happen but usually the lesion regresses and
the loss of visual acuity is moderate. In the majority of the
cases both eyes are affected, the unilateral disease is
infrequent [6]. In the atypical Cogan syndrome the vestibulo-
cochlear manifestations can be associated with scleritis,
episceritis, uveitis, optic neuritis, conjunctivitis or glaucoma.
[7]
Vestibulo-cochlear symptoms: Cogan syndrome is classically
characterized by sensory-neural hearing loss, vertigo and
1 St Maria General Hospital, Bucharest, Romania 2 Carol Davila University of Medicine and Pharmacy, Bucharest, Romania 3 Carol Davila University Emergency Central Military Hospital, Bucharest, Romania
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67
tinnitus in an association that resembles to Meniere’s
disease. The hearing loss might be profound, leading to
cophosis in almost 52% of cases and usually it is bilateral. The
auditory deficit is installed in days, months, too slow for a
sudden nerosensorial hearing loss and too quick for a
presbyacusys. The speech discrimination scores are poor.
The hearing loss is associated with tinnitus. [4]
The vertigo can be important causing marked instability,
ataxia, sometimes associated with nausea and vomiting. The
nystagmus can be observed at the ocular examination. In
most of the cases, complains are similar to Meniere’s
disease.
Other signs and symptoms
General manifestations of the disease are not rare, fever has
been reported in many cases, weight loss and extreme
asthenia can be found in patients with Cogan’s.
Cardiac involvement, especially aortic insufficiency is
present in as much as 15% of cases. Large vessels can also be
affected causing heart murmur, abdominal pain,
claudication of the members.
Musculo-scheletal involvement manifests as myalgia or
arthritis (mono, oligo or polyarthritis).
Neurological signs appear in ¼ of cases [8], patients might
have paresis, hemiplegia, aphasia, cerebellar syndrome,
pyramidal syndrome, spinal cord disorders, epilepsy, and
vigilance disorders. MRI can sometimes detect lesions of the
white matter consistent with cerebral vasculitis.
Cutaneous lesions might appear during attacks taking the
form of urticarial rash, vascular purpura, ulcerations or
nodules.
Some patients might have gastro-intestinal or pulmonary
symptoms.
Laboratory investigations
Biologic parameters can be modified in Cogan syndrome,
especially during the attacks, but no laboratory test in
pathognomonic for the disease. Leukocytosis, elevated ESR,
anemia, hyperfibrinemia may appear. Several immune-
logical modifications also can be noticed: rheumatoid factor,
antinuclear antibodies, cryoglobulins, lupus anticoagulant
but none of these are specific or relevant for the disease. [9]
In small series of patients, some authors determined the
presence of specific antibodies for the inner ear or cornea
but these studies were not relevant and could not be
reproduced by other authors so cannot be used to support
the diagnosis of Cogan.
Differential diagnosis
The first differential diagnosis one should bear in mind when
facing a rapid onset hearing loss with vestibular symptoms
and interstitial keratitis is syphilis. Another important
differential diagnosis is Meniere’s disease but in this case the
ocular manifestations are absent.
Another diagnosis to be differentiated from Cogan is Susac
syndrome, a retino-cochleo-cerebral vasculopathy involving
the arterioles, manifested by central neurological disorders,
visual acuity loss, and hearing loss.[10] Vogt- Koyanagi-
Harada syndrome is characterized by uveitis, alopecia,
vitiligo and audio-vestibular symptoms.[11] . Other systemic
diseases such as Wegener granulomatosis, PAN, relapsing
polychondritis, Behcet disease, and Sjogren syndrome can
associate vestibulo-auditory symptoms with ocular
involvement.
Evolution, prognosis
In some cases, the onset of the disease is preceded by upper
respiratory tract viral infection.
The vestibular and auditory symptoms can be the first
manifestations of the disease in 41% of cases. in 43 % of
cases the Cogan syndrome debuts with the ocular
symptoms. The involvement of the two organs is usually
done in approximately 3 months [8]. In cases of atypical
Cogan syndrome the complete symptomatology might be
installed in a long period, even years.
Usually, after the first attack the disease enters a phase of
remission without evident symptomatology. There is a
possibility that there are recurrent episodes that repeat at
variable intervals. Once installed the hearing loss is not
remissible. The vestibular symptoms diminish as a result of
the compensation mechanisms. The ocular symptoms have
a variable evolution, but usually respond favorably to
treatment.
Treatment
As the etiology and the pathogenic mechanisms are not
known, there is not yet available a codified treatment for
Cogan’s syndrome.
Usually the first line of treatment is represented by
corticosteroids. [12] In cases where the corticodependence
is installed or in cases of corticoresistance there is the
possibility of using other therapeutic agents such as
immunosupressants (cyclophosphamide, azathioprine, and
methotrexate). [13] The corticotherapy should be prescribed
in high dosage (1-1.5 mg prednisone or equivalent) and
interrupted in two weeks in cases where it is ineffective.
Studies show that the vestibulo-cochlear symptoms respond
68
to treatment only in one third of the cases (orphanet). Once
the deafness is installed, it is usually non-reversible.
In the last years there were attempts to treat Cogan
syndrome with TNF alfa blockers but there are not enough
evidence based results [14, 15]
CASE REPORT
We present the case of a 40 years old woman with no
remarkable medical history who presented at the
emergency department of our hospital accusing sudden
onset intense vertigo and dizziness, tinnitus and hearing loss
in the right ear. The patient was admitted in the ENT
department.
The physical examination of the patient yielded no relevant
data, the ENT exam was within normal limits.
The vestibular examination pointed out to an important
instability, the patient was unable to maintain orthostatic
position or walk without support, no spontaneous
nystagmus.
The cerebral IRM examination did not reveal any vascular or
tumoral lesions. The neurologic examination did not
discover any motor or sensorial deficit, no signs of
localization.
The audiogram performed initially can be visualized in Figure
1. We diagnosed a profound sensoryneural hearing loss for
the right ear and a medium sensory-neural hearing loss for
the left ear.
Figure 1: Initial audiogram
The rheumatologic examination revealed no remarkable
findings: no arthritis, no cutaneous lesions, and no ocular
symptoms.
The blood hematological and biochemical parameters were
modified showing a slight leukocytosis with a white blood
count of 11000/mm3, the ESR also slightly elevated 25
mm/hour and the CRP had the value of 5. The modifications
were interpreted as a reaction to an acute dental infection
the patient had at that moment.
All the immunologic tests we performed were in normal
limits, IgA, IgG, IgM, ANA, antibodies anti beta 2
glycoprotein, antibodies antiphospholipid were tested and
the values were normal. Antibodies Ig M and Ig G for Epstein
Bar virus, Toxoplasma, HIV, herpes virus, cytomegalovirus
were all negative.
The ophthalmologic examination did not find any
modifications of the anterior ocular pole at that initial
moment.
The computerized posturography we performed at
admission showed a severe vestibular deficiency pattern
(Figure 2).
The videonystagmography with caloric testing evidenced a
total right areflexia and an extremely important left
hyporeflexia (Figure 3).
We started a treatment with high dose corticotherapy (solu-
medrol), antiemetic (osetron), vestibular suppressant
(diazepam), vasoactive agent (pentoxyphilin), vitamin (B1
and B6), plasma expander(dextran 40).
During the treatment, the patient presented a fluctuating
evolution. The hearing level fluctuated especially on the left
ear with PTA between 30 and 60 and on the right ear with
PTA between 60 to 90.
In Figure 4 it can be noticed the aspect of two audiograms
we performed during the treatment in which we could
observe the fluctuant hypoaccusis in both ears.
The dizziness also fluctuated with episodes of severe vertigo.
In these episodes, the direction of the nystagmus varied. We
recorded horizontal rotatory nystagmus beating to the left
but also to the right (Figure 5) alternating with periods of lack
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69
of nystagmus.
Figure 2: Computerized posturography
Figure 3: Videonystagmography
Figure 4: Audiograms during the treatment
70
Figure 5: Horizontal rotatory nystagmus beating to the left but also to the right, alternating with periods of lack of nystagmus
After 10 days of treatment in the hospital, the patient was
discharged with an improvement of the hearing loss in the
left ear, no vertigo and only a mild dizziness.
One month after this episode, the patient presented once
again at the emergency department accusing intense
vertigo, nausea, vomiting, tinnitus and aural fullness in the
left ear. The audiogram evidenced a bilateral severe hearing
loss (Figure 6).
Figure 6: Bilateral severe hearing loss
The rheumatologic examination did not reveal any
modifications. The second day of hospitalization the patient
suddenly presented eye pain with intense redness of the
conjunctive. The ophthalmologic examination established
the diagnosis of kerato-conjunctivitis (Figure 7).
In this moment, we were able to diagnose an atypical Cogan
syndrome taking into account the association between the
audio-vestibular symptoms with an inflammatory ocular
disease.
We repeated the same treatment as in the first episode
associating local eye topical corticosteroids and artificial tear
solution with a major improvement of the hearing loss for
the left ear PTA 10 (Figure 8).
The patient was discharged with a prescription of
prednisone in low dose for a period of three months.
One year later, in the follow up, we noticed that the hearing
in the right ear did not improve at all but the instability
improved a lot so the patient was able to continue with
everyday life. In this year she did not have any attack, no
audiovestibular or ocular symptoms.
DISCUSSION
Haynes et al described atypical Cogan syndrome for the first
time in 1980. The typical Cogan syndrome was described as
an association between Meniere–like audio-vestibulary
symptoms and non-syphilitic interstitial keratitis with an
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71
interval between the onsets of the symptoms of less than
two years.
Figure 7: Kerato-conjunctivitis
The atypical Cogan syndrome consists in an association of
symptoms in which the disease criteria are grouped as
follows:
• Inflammatory ocular manifestations with or without
interstitial keratitis
• Typical ocular manifestations associated with audio-
vestibular symptoms different from Meniere’s
• A delay of more than 2 years between the onset of typical
ocular and audio-vestibular manifestations.
The atypical Cogan syndrome with ocular manifestations
other than interstitial keratitis tends to have a higher rate of
systemic involvement with aortitis and has a worse
prognosis. [3, 16]
It is the case of a 40-year-old woman with acute onset of
intense audio-vestibulary symptoms with no remarkable
medical history and no other general manifestations. At the
first presentation the diagnosis of presumption was Meniere
disease but there were characteristics of the evolution that
did not entirely correspond. The disease was rapidly onset
with bilateral and unequal involvement. The right ear had a
profound hearing loss from the very beginning and
practically did not respond to treatment. The left ear had a
minor amelioration in the first episode and quite a good
response in the second episode of the disease although the
treatment was similar. During the admission we performed
multiple audiograms evidencing the fact that the thresholds
at both ears were in a continuous modification, not
respecting the classical pattern of Meniere’s. The
videonystagmography with calorics showing bilateral
vestibular lesion from the beginning of the disease, was also
atypical for Meniere.
Figure 8: Major improvement of the hearing loss for the left ear
The onset and evolution of the disease made us believe that
there is a autoimmune disorder of the inner ear but we did
not have any disease criteria to classify. The laboratory tests
were within normal limits, the minor leukocytosis and the
slight elevated ESR were not noticeable. No other
immunologic tests were modified or virus infections
detected.
At the second episode of disease, the concomitance with the
kerato-conjunctivitis was consistent with the diagnosis of
atypical Cogan syndrome. We consider that this is the only
disorder that can be taken into account for the diagnosis of
this patient. Another remark is the fact that the patient is
over the age of typical onset of the disease, but there are
many reports of atypical Cogan with patients in the same age
group. [17, 18]
The response to corticotherapy, was partial as the right ear
did not recover, but the final result was considered
satisfactory by the patient who could continue her daily
activities.
72
CONCLUSION
Although Cogan syndrome is a rare disease, we must bear in
mind that there is always a possibility of diagnosing it in the
case of a patient with both vestibule-auditory symptoms and
ocular manifestations.
Typical and atypical Cogan syndrome are diagnosed mainly
based on clinical criteria as there are no laboratory tests able
to evidentiate the disease.
The treatment consists mainly in corticotherapy. Immuno-
suppressants are an option in cases where corticotherapy is
inefficient.
References:
1. Morgan RF, Baumgartner CJ. Ménière’s disease complicated by
recurrent interstitial keratitis: excellent result following cervical
ganglionectomy. West J Surg 1934;42:628-31.
2. Cogan DG. Syndrome of nonsyphilitic interstitial keratitis and
vestibule-auditory symptoms. Arch Ophthalmol 1945;33:144-9.
3. Haynes BF, Kaiser-Kupfer MI, mason P, Fauci AS. Cogan
syndrome studies in thirteen patients, long term follow-up, and
review of the literature Medicine.1980 69426-41
4. M. B. Gluth, K. H. Baratz, E. L. Matteson, and C. L. W. Driscoll,
“Cogan syndrome: a retrospective review of 60 patients throughout
a half century,” Mayo Clinic Proceedings, vol. 81, no. 4, pp. 483–488,
2006
5. J. Cundiff, S. Kansal, A. Kumar, D. A. Goldstein, and H. H. Tessler,
“Cogan's syndrome: a cause of progressive hearing deafness,” The
American Journal of Otolaryngology, vol. 27, no. 1, pp. 68–70, 2006
6. R. M. McCallum and B. F. Haynes, “Cogan's syndrome,” in Ocular
Infection & Immunity, J. S. Pepose, G. N. Holland, and K. R.
Wilhelmus, Eds., p. 446, Mosby, St. Louis, Miss, USA, 1st edition,
1996
7. A. Grasland, J. Pouchot, E. Hachulla, O. Bletry, T. Papo, and P.
Vinceneux, “Typical and atypical Cogan’s syndrome: 32 cases and
review of literature,” Rheumatology, vol. 43, pp. 1007–1015, 2004
8. P. Vinceneux, Cogan Syndrome, Orphanet Encyclopedia, 2005
9. R. S. Vollertsen, T. J. McDonald, B. R. Younge et al., “Cogan's
syndrome: 18 cases and a review of the literature,” Mayo Clinic
Proceedings, vol. 61, no. 5, pp. 344–361, 1986.
10. Kleffner I, Dörr J, Ringelstein M for the European Susac
Consortium (EuSaC), et al Diagnostic criteria for Susac syndromeJ
Neurol Neurosurg Psychiatry;87:1287-129. 2016
11. Andreoli CM, Foster CS. Vogt-Koyanagi-Harada disease. Int
Ophthalmol Clin. Spring. 46(2):111-22. 2006
12. E. W. St. Clair and R. M. McCallum, “Cogan's syndrome,” Current
Opinion in Rheumatology, vol. 11, no. 1, pp. 47–52, 1999
13. L. Riente, E. Taglione, and S. Berrettini, “Efficacy of
methotrexate in Cogan's syndrome,” Journal of Rheumatology, vol.
23, no. 10, pp. 1830–1831, 1996
14. Z. Touma, R. Nawwar, U. Hadi, M. Hourani, and T. Arayssi, “The
use of TNF-α blockers in Cogan's syndrome,” Rheumatology
International, vol. 27, no. 10, pp. 995–996, 2007.
15. M. Fricker, A. Baumann, F. Wermelinger, P. M. Villiger, and A.
Helbling, “A novel therapeutic option in Cogan diseases? TNF-α
blockers,” Rheumatology International, vol. 27, no. 5, pp. 493–495,
2007.
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Araújo, and Angelina Meireles, “Atypical Cogan's Syndrome,” Case
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JOtolaryngol. Jul-Aug;31(4):279-82. 2010
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Article received on May 3, 2019 and accepted for publishing on June 30, 2019.
VARIA
Patient-physician communication, an essential condition for an effective medical act
Carmen M. Voicu1, Consuela M. Gheorghe1
An inconceivable reality for the medical world today is to
consider the patient an active factor in his own healing
process. Placement of the patient in the center of healthcare
services aims at his loyalty, which means creating and
maintaining correct and long-lasting relationships with him.
In addition, in order to create such relationships with
patients, both loyalty and stability, performance, and
profitability strategies of the medical team must be thought
on long-term.
Healthcare marketing situations differ, and medical units
concerned with the essence of success must strive for a
strategic alignment of relationships between all
stakeholders (decision-makers, medical staff, patients, etc.)
and the power of these relationships to improve their
mutual value and even the relational context as a whole,
turning patients into true brand promoters, thus enhancing
marketing efforts [1].
The patient reaches to attitudes, judgements, and
preferences about certain brands through a procedure of
evaluating the features of these brands, developing a set of
beliefs about the features that correspond to each brand [2].
Recognition of the strategic relationship that a patient
desires is a medical marketing reality and involves greater
commitment to accepting the challenge of creative thinking
in often difficult situations, progressing through knowledge
and understanding to mutual trust, converting emotions into
balanced normality and the relationship thus created into an
emotional-connected and loyal one for a certain period of
time. This means concentrating efforts on patients,
attention, and receptiveness to his wishes, but
professionalism and rigor in such a way that his personal
health expectations are not in vain. Moreover, it is very
important to pay a close attention to communicating with
him; it is even said that this type of communication is the
broker of the relationship developed in a sensitive and
dynamic environment like the healthcare field.
The complexity of providing healthcare services, on the one
hand, and the wishes and expectations of patients, on the
other hand, have as result special patient-physician
communication valences and turn it into an essential
condition. Permanent and effective communication with
patients has become a condition of the existence of a
qualitative medical act.
Given the continuous increase and diversification of health
services, communication issues are becoming increasingly
difficult and require much more laborious information
efforts.
Due to the information explosion, patients tend to
appreciate the quality of a product or service based on
perceptions rather than on reality.
That is why efforts to optimize the technological and
informational processes of communication between
patients and medical staff, of exploring patients’ behaviors
regarding interpersonal communication in electronic
environments in health services, of modeling negative
emotions, of ways of transforming the healthcare
infrastructure so that it offers an integrated insight of
information through the optimized clinical and business
processes, of welfare and health management, of patient-
centered networks, of investigating the influence of virtual
communities on the reputations of health organizations in
Romania, has become a permanent necessity [3].
74
The relationship between the two sides, medical staff-
patient, in the healthcare field, is much more complex,
addressing social, psychological, and cultural aspects, which
besides the base of the therapeutic level also implies a
superior level of existential communication. The latter is
found in medical communication because the medical act
interferes with the destiny of the patient, linked in turn with
elements of uncertainty and individual instability [4].
Interpersonal communication was the first spiritual
instrument of the human being in the process of socializing,
and is defined as the communication that occurs between
two people in the context of their relationship and which, as
it evolves, helps them negotiate and define the relationship
[5].
Communication within the health organization takes place in
a complex environment, where continuously modifying
favorable and unfavorable factors coexist. Communication
can take many forms and can be seen in different situations,
but the most important of these is undoubtedly between
patient and physician, which provide much of the data
needed to establish the diagnosis and therapeutic attitude.
Interpersonal communication is formed by the combination
of verbal forms (oral and written), nonverbal forms
(gestures, mimics, posture, movement, aspect) and
paraverbal forms (by voice attributes accompanying the
word, such as intonation, rhythm, verbal flow), but,
considering the importance of the information content of
patient-physician communication (the diagnosis and
treatment process), in the medical system, the emphasis is
more on verbal communication. Non-verbal and paraverbal
forms are important from the point of view of their
emotional effect and the formation of sympathy.
In the health system, the relationship between the two sides,
the medical staff-patient, is much more complex, involving a
higher-level therapeutic type of existential communication.
This type of communication [4] is involved in medical
communication, because the medical act interferes with the
destiny and evolution of the patient, being in turn linked to
elements of uncertainty and individual instability.
On the other hand, the position of the two entities, namely
the medical staff-patient, is different and unequal [6]. This
relationship is established between members of two distinct
social groups in terms of their prestige, power, and
orientations. Thus, the physician has an extremely high
status, given the level of information held and the
specialized guidance through which he exercises his full
authority.
The social role of the patient demonstrates his vulnerability,
being forced to seek support whenever he needs. Thus, the
patient is the most disadvantaged person, being influenced
by physical and mental suffering, feeling the disease as a
source of uncertainty and insecurity, while the physician is
regarded as a person with multiple qualities, full of energy
and sometimes with magical powers.
Gaining a high communicative competency needed by the
specialist to create a real therapeutic alliance requires not
only solid medical knowledge to diagnose and treat the
disease but also the ability to obtain as much information as
possible from the patient and interpersonal skills to respond
to feelings and patient concerns and the ability to create and
maintain the therapeutic relationship as a concrete offer of
information and medical education [7].
Health communication is “the study and use of
communication strategies to inform and influence the
choices people make regarding their health”, and health
information technology includes “digital instruments and
services used to enhance self-care of patients, assisting
patient-provider communication, informing about health
behaviors, preventing health complications and promoting
equity in health” [8].
A major concern of health services and primarily of hospitals
has become communicating with patients, the quality of
information provided to patients by physicians and the rest
of the medical team. An essential component is the
transmission of information, which has become increasingly
important in medical deontology. This development is
primarily driven by wishes of patients, more trained in health
issues, and more cautious about the quality of the
explanations they are given.
In the hospital environment, where the patient is subject to
the attention of medical teams, the coherence of “what is
said and what is not” becomes a permanent goal for patients
and their relatives. Because, beyond anything “...there is an
informational asymmetry between the physician and the
patient: when they find themselves in the hospital (...), they
feel ill, they do not feel what is going on with them, they do
not know the possibilities of medical science, so they
empower the physician with the freedom of choice” [9]. A
good professional behavior is to state exactly how we are
feeling and to write what we are saying. However, each
physician is the supreme judge of how he or she does and
can enrich his or her oral information by using information
charts and, if considered necessary, by other documents or
video support.
In healthcare services, access to online information has
made patients more aware of their needs and desires so the
result has materialized in a rigorous selection of service
Vol. CXXII • No. 2/2019 • August • Romanian Journal of Military Medicine
75
providers.
Therefore, healthcare managers and providers need to
understand the stages a potential patient is going through in
an online buying process or when expressing an intention to
buy an online health product or service.
The winners will be those who build trust from the patient’s
perspective, with three progressive complex components in
the relationship between the brand and him: credibility,
care, and congruence. Certainly, what is very important is
the amount of money spent by the patient for the recovery
of health.
Nowadays, in health systems, the widened marketing mix
enjoys considerable attention. It provides a simple
organizational mechanism to understand the problems
arising from the concerns of medical service providers. The
widened mix has also developed as a partial solution to some
of the most important problems faced by managers in terms
of quality control of healthcare services provided and the
relationship with patients in the process of providing these
services. The widened mix explicitly recognizes the role of
the staff and patients in the service delivery process,
highlighting the role of marketing played by both sides.
The inclusion of Physical Evidence, Participants, and Process
as distinct (contextual) elements underlines their
importance and impact on marketing of health services. In
addition, the key objectives are to increase patient
satisfaction, quality of medical services offered and long-
term patient gaining, which means that the widened
marketing mix management is directly related to these
objectives.
Due to the immaterial nature of healthcare service and the
fact that, usually, they cannot be checked beforehand,
patients are looking for tangible evidence of what they are
about to experience in a particular immediate confrontation
with the medical service. Even if a patient has a high
experience with such a healthcare provider, variations, and
contextual elements will affect patient’s expectations
related to the immediate confrontation with a medical
service.
Elements of “Physical Evidence”, such as noise level, smell,
temperature, time, comfort, and even nutrition, will
influence the perceptions of confronting with the healthcare
service requested. Similarly, the attitudes and behavior of
healthcare participants will influence the perceptions of
current performance. Contextual elements can also
influence satisfaction in the confrontation with the medical
service, through their effects on attributions (of causes) for
invalidation. Theory of attribution asserts that when results
are not in line with expectations, people tend to look for
reasons. The importance they give to “why”, will influence
the final evaluation of the outcome.
The communication process is very important within the
medical unit; it is a process that affects the quality of the
other processes. Through the positive impact on
communication within the medical unit, the style oriented
towards maintaining socio-emotional aspects and the
leadership style oriented towards relationships is beneficial
to the processes within the medical unit and to the
emergence of positive socio-emotional states. This
leadership style is associated with the existence of high
quality communication relationships, which leads to the
improvement of the quality of the other processes [10].
In the new context of health, development processes will
need to focus not only on solving current problems, but also
on anticipating future problems, not just on certain types of
processes, but as many as possible, not just on technical
resources, but more on human ones. Organizational-
managerial excellence seeks not just the adaptation to
circumstances, but also the becoming and the power to
create the circumstances [11].
The depth of the process of change in health, its size, and its
dynamics depend not only on the political will and on the
subjective aspirations, but also on the existence and
sufficiency of the necessary objective conditions, the
managerial ones being the first.
In the context of today’s healthcare problems, the special
role of the manager is imposed by the need to create a
general capacity for innovation, flexibility, stability, and
ensuring success even in extreme situations. In this context,
the theoretical but especially the methodological approach
of the marketing of the medical system has special practical
valences, requiring a change in the mental attitude of health
managers towards an innovative strategic hospital
marketing oriented towards and for the benefit of patients
[12].
References:
1. Batterley R. Leading Through Relationship Marketing. 2004,
McGraw-Hill Australia Pty Ltd.
2. Kotler P, Shalowitz J, Stevens RJ. Strategic marketing for Health
Care Organizations - Building a Customer – Driven Health System.
2008, Jossey Bass A Wiley Imprint.
76
3. Purcarea VL. Impactul tehnologiilor informationale asupra
sistemului de sanatate. Teza de abilitare, 2013.
4. Cosman D. Psihologie medicală. 2010, Iaşi, Editura Polirom.
5. Floyd K. Comunicarea interpersonală. 2013, Iaşi, Editura
Polirom.
6. Chichirez CM, Purcărea VL. Interpersonal Communication in
Healthcare. Journal of Medicine and Life. April-June 2018;
11(2):119-122.
7. Servellen van GM. Communication skills for the health care
professional: Concepts, practice, and evidence. 2009, Canada, Jones
& Barrlett Publishers.
8. https://www.healthypeople.gov/2020/topics-objectives/
topic/health-communication-and-health-information-technology.
9. de Kervasdoné J. La generalité de soin on France. 2000, 46.
10. Curşeu PL, Schalk MJD, Wessel I. How do virtual teams process
information?. A literature review and implications for management.
Journal of Managerial Psychology. 2008; 23,6,628-652.
11. Ciurea AV, Ciubotaru VG, Avram E. Dezvoltarea
managementului în organizaţiile sănătăţii. Excelenţa în serviciile de
neurochirurgie. 2007, Bucureşti, Editura Universitară.
12. Popa F, Purcarea Th, Purcarea VL, Ratiu M. Marketingul
serviciilor de ingrijire a sanatatii. 2007, Bucuresti, Ed. Universitara
”Carol Davila”.
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Article received on May 12, 2019 and accepted for publishing on June 30, 2019.
VARIA
The tree we throw stones at
Mihail Mihailide
I stop to catch my breath on the crest of a hill in Predeluţ.
It's late autumn with a blue-diamond sky. Nevertheless,
there is fresh snow fallen on the rugged tops of the
mountains and on the hedges of dark fir trees at the foot of
the Bucegi mountains – looking as if they were mounted
lancers. The snow is glistening.
I feel the tall grass, dried by the season, under my feet. On
the twisted and black branches of the old apple trees, red
fruit swing in the scented wind. Around the roots of the
some apple trees – there are spots of royal purple perennial
irises. Although poisonous flowers, I can’t resist their calling
beauty and I lift a few threads.
Back on track, I turn my bicycle towards Bran, I descend by
the Castel, pass by Vama Medievală, and ride along Turcu
River to the place where it sweeps in Șimon stream. Then I
turn left and head towards the Brandeberg guesthouse. Here
I securely park my "Pegas". My destination is not the hotel
but the building across the street, Parascheva Holy Church,
on 340, Iancu Gonţea Street, whose frescoes were painted
about three centuries ago by Nicolae Zugravu from Turcheş
– Săcele. It is believed that he also put his talent at work at
the Three Holy Hierarchs Monastery in Iași.
My objective as a traveller is not the church but the "cultural
and medico-historical heritage" provided by the resting
places around this holy edifice. Many important Romanian
intellectuals – several of them physicians – were born in the
village of Bran, today a tourist attraction, but also in the
nearby villages; many sleep their eternal sleep in the
cemetery of Şimon village, under crosses with their names
engraved on them. I intend to leave the bunch of irises on
Iancu Gonţea’s grave… The surrounding mountains and the
forests that reached the yard of my house when I was a child
were like the lords of the land for me... It is at Şimon that I
built a vault in order to make sure that I would not sleep my
eternal sleep anywhere else. "Today, a commemorative
plaque and the name of a street in Bran remind us of this son
of the region”, noted Emil Stoian, the brave chronicler of this
beautiful mountain village, to whom the inhabitants owe a
major contribution for preserving the image of those who
really meant something for the Romanian people. Such
people are numerous, in Bran: historians, philologists,
lawyers, physicians, actors, officers, priests, professors and
academicians; participants in the Great Union of 1918;
heroes of the two World Wars. I have met some of the
physicians…
78
Found at the location, I feel disappointed: where is the
tomb? I am told to go two kilometers uphill on the right side
of the road. This time I decide to walk. Indeed, after passing
the Primary School, on the yellowish wall of which a thin
marble plaque reminds that the scholar attended his first
classes "here", I pass by the house and the yard where he
was born and spent his childhood, its gate always locked, and
arrive at the church dedicated to St. Nicholas, standing a few
meters retreated from the main street. Here, behind the
building is a small cemetery. At its end, close to the hill, I
finally find the vault: "Fam. Prof. Dr. Doc. Iancu Gonţea" with
two rows of vertical crypts! It looks rather like a bunker. In
the crypt by the side of the teacher lies his wife, Dr. Lucia L.
Gonţea (1907-1998, born Popescu) buried 22 years after the
professor.
From an oval photograph, embedded in the austere concrete
wall, the professor gives me a harsh look. Where should I put
the irises brought as a modest homage? It's difficult to find
your way between the graves...
I have synthesized ergo-biographical data regarding Prof.
Iancu Gonţea in a book [2], using sources coming mainly
from the archives of the medical-historical documentation
library of the National Public Health Institute of Bucharest,
an institution whose enrichment with new information
(manuscripts, photos, video tapes, books, magazines, etc.)
and modern digitization was stopped for various reasons...
Iancu Gonţea was one of my professors in my fourth year at
the Bucharest Faculty of General Medicine. Decades have
gone by. Before proceeding to "serious things", I ask the
reader's permission to reproduce a few paragraphs, surely
forgotten by the reader, perhaps funny, from the notes
about the professor of the Food Hygiene Department, who
was born in Şimon and returned there at the end of his life.
"We were two groups of fourth-year students of General
Medicine, huddled in front of the laboratories of the
Institute of Hygiene in Bucharest, where we were to take an
oral exam in Food Hygiene. The professor – an unforgettable
person... tall, slim, with penetrating eyes and a Hemingway-
style beard, wearing an impeccable white gown – was sitting
at the teacher’s desk, on a podium, with the assistant group
on his right, and us, the wretched students (oh, how we cried
out for mercy knowing his exigency!), one step down, in
front of the examiners, at a tiled table full of Erlenmeyer
balloons, pipettes, tripods, test tubes and dropping bottles.
Usually, this type of final exam was the responsibility of the
associate professors. It was only exceptionally that the
professor would waste his time with us. Well, there we were,
living... the exception! Each of us picked from a jar the ticket
with the subjects written on it, thought of them for a few
minutes and answered the three questions, in the order in
which they were typed.
After ending our monologues (rather scanty, more often
than not), followed a dialogue with the professor, Iancu
Gonţea himself. At the end, he wrote down the grade that
each of us deserved in our grade-books and we tiptoed out
of the lab. In the hall, we were approached by our classmates
who, browsing through their notebooks, were trying to learn
everything they hadn’t learnt until then, before entering the
lab room „to have their heads cut off".
– What subject did you pick? Does he also ask questions from
«the practical experiments»? Is he harsh, is he kind? What
grade did you get? Many of the questions were difficult to
answer promptly... At a certain moment, one of the best
Vol. CXXII • No. 2/2019 • August • Romanian Journal of Military Medicine
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students of our class came out of the lab, almost bursting
into tears, obviously confused.
– What happened? What subject did you get?
– The third question, she explained us, as she started to feel
better, was about the trophic content of the main foods. I
explained how many proteins, lipids, fats and calories can be
found in cow's milk, eggs, fish, chicken and I don’t know what
else I mentioned... I couldn’t realize whether he was satisfied
or whether I had gotten it all wrong. I finished what I had to
say, but then he asked me additional questions, looking at
me over his glasses:
– «What about ordinary vegetables, which of them have a
higher vitamin content?» I gave the wrong answers, I
stammered and then I said: carrots, spinach, tomatoes...
Whatever!
– «What a-bout-par-sley?» he asked. I was as quiet as a fish.
Total silence. He gave me the right answer and explained
why his question was so important. Then he added:
– «Veronica, Veronica! You didn’t really like Food Hygiene…»
And then I saw him write 5 (five) in my grade-book and sign
it. «You should come in the autumn to get a higher grade! he
said, probably thinking that I would otherwise lose my
scholarship…
The professor's question was not tricky, he had indeed told
us in his lectures that parsley contains more vitamin C than
lemon, orange or cabbage and, in addition to that, it also
contains vitamins A, B1, B2, B6, K and E, as well as all the
minerals useful to the body. Parsley is an antioxidant,
antiallergic, antitumoral, which stimulates the gallbladder
secretion, maintains elasticity of the vessels, and I can no
longer remember now, more than half a century later, what
other wonders we owe to this herb, commonly used for
flavoring and adorning dishes!
Veronica had only remembered what the professor’s
assistant had told us at a seminar, smiling, about the
qualities of this ancient vegetable: «It also ensures the good
functioning of the genitals and even has a powerful
aphrodisiac effect! »”[3]
Writing about himself in a curriculum vitae requested by the
Academy of Medical Sciences (AMS), whose member he
became, professor Iancu Gonţea believed that he had set a
"new trend in the science he practiced, which was seen not
only as food hygiene, studied separately from the man (in a
narrow technical-sanitary concept), but as the science of
biomedical, psycho-social, and economic relations between
man and food"[4]. He has the merit of having contributed to
determining the nutritional requirements in relation to one's
occupational and environmental conditions, «for the first
time demonstrating that physical activity increases protein
and calcium needs, as well as vitamin C consumption, [and
that] exposure to chemical noxae heightens the metabolism
of thioamide acids and of ascorbic acid, increasing the needs
of the body.»
In the same CV requested by the Academy of Medical
Sciences, the professor listed the procedures he had devised
for the biochemical control of vitamin nutrition status, as
well as the methodology for studying the biological value of
food, both highly appreciated by international scientific
bodies.
The professor was to be awarded an important international
prize (Maurel) as well as the silver medal in food science for
his contribution regarding natural anti-nutritional
substances in food and animal feed. I. Gonţea also
demonstrated that no food is complete and set up an
original classification of foods (by groups), embraced by
experts of his time, in keeping with the benefits and the
deficiencies of various food categories."[5]
Given their originality and practical value, based on rigorous
laboratory and field research, many of his writings have been
translated into widely-circulated foreign languages. They
cover the fields of effort physiology, pathophysiology, and
medical clinic, but most of them include research on human
nutritional needs under different physiological, occupational
and environmental conditions: "Food Control" (1956), "Food
Ration" (1956), "Rational Nutrition of Women during
Maternity and Its Importance for Mother and Child Health"
(1958) can be considered as major landmarks in medical
literature, at least in the Romanian one. The last of the books
mentioned were updated by the author, translated into
German, and published by the prestigious publishing house
80
Gustav Fischer of Jena in 1965. Having received excellent
reviews, this monograph was requested, from the German
publishing house, by Dai-lichi Co. Ltd. Publishing House in
Tokyo and became the first book by a Romanian scientist
published in Japan, in 1974.
In 1963, the Medical Publishing House (Bucharest) released
"The Bases of Nutrition". Three years later, another book
was published: "Natural Anti-Nutritional Substances in Food
and Animal Feed" (in association with Paraschiva Şuţescu,
Ph.D.), subsequently translated into French and published by
Vigot Frères Publishing House, in association with prof.
Raymond Ferrando PhD (Paris, 1967), as well as into English,
and published by Karger Publishers in Basel (Switzerland) [6]
as well as in New York (1968). The Academy of the Socialist
Republic of Romania awarded professor Gonţea the "Victor
Babeş” prize for this book. Among the books that were
published, almost every year, two titles still stand out,
several decades later:" A Genetic Leap in the Nutritional
Value of Corn – the Past and Present of this Cereal” (Ceres
Publishing House) and "Alcoholism" (Medical Publishing
House, 1976), an insight from the point of view of preventive
medicine into the use and over consumption of alcoholic
drinks – "considered to be a serious problem on a national
level".
Professor Iancu Gonţea won high recognition in the scientific
events he was invited to — international congresses and
symposiums (Dresden, Moscow, where he accompanied the
Romanian delegation as an expert in nutritional issues at
C.A.E.R. meeting, 1969), at New Castle ("Women’s Nutrition
during the Reproductive Cycle", 1971), Mexico (where he
presented a paper titled "Nutrition and Anti-Infectious
Defense in Humans" ), Austria ("The Effects of Sugar Abuse")
etc. He received national and international awards and
diplomas.
Under a Decree of the State Council of the Socialist Republic
of Romania (153/1971), the professor was awarded the
"Sanitary Merit”, alongside other scientists rewarded "for
the contribution to the Party's policy in the field of public
health in our country". The chairman of the Council at the
time was N. Ceauşescu, while the minister of health – Prof.
Dr. Dan Enăchescu.
The fact that the romanian scholar did not also become a
member of the Academy is rather amazing, since, forgive my
insolence, many others were comfortably sitting in the
"immortals"' seats of the Academy of the Socialist Republic
for (scientific!) achievements, which, compared to his own,
were a lot less significant...
*
Who would have thought that professor Iancu I. Gonţea – a
former military physician (promoted major in 1948), hence
a person whose past and family had been under the close
scrutiny of the army's newly set-up personnel department
and who had a "healthy" origin (being the son of a shepherd,
born in the village of Şimon, on February 10, 1907), and
therefore, seeming to be imbued with socialist "principles"
and "ethics" – was to be placed under surveillance by the
Securitate (being the subject of two files, "I. 498910")? [7]
He maintained correspondence with scientists from all over
the world; often travelled to Western countries but also to
the Soviet Union; he attended medical conferences; worked
in the field of food hygiene, this having a great social impact.
He represented the Socialist Republic of Romania in the
World Health Organization. All this supposed that his loyalty
to the "party and to the socialist homeland" were to be
continuously tested by the "state bodies"...
The "vigilance" of the Securitate also translated into an
internal decision issued on November 18, 1969, regarding
the preservation of his "informative" file in the Operational
Fund, under no. I. 715753, coming from the 3rd Directorate
of the feared institution…
What was pursued Iancu Ion Gonţea accused of?
That "he was a member of the Iron Guard, working in the
Sanitary Department of its Documentary Studies Center."
That, "he was a major in the bourgeois army" (a member of
the contingent of officers who took the military oath before
the King). Later on that "he maintained correspondence with
people from abroad, such as Prof. R. Ferrando (France) and
foreign publishing houses." In an informative ("strictly
secret") note obtained by major I. Ion, at agent "Gabriel"
home and dated April 17, 1967, he declared that he met the
person under surveillance during his studies at the Andrei
Şaguna High School (1924-1927) and added that Iancu
Gonţea (I.G.) "was a very good student, who graduated at
the top of his class".
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The note provided biographical data, generally consistent
with that provided by Gonţea in his résumés. I.G. seems to
been the son of poor peasants from Bran; he was not
perform any legionary activities, although his uncle, a history
teacher, dr. [Ioan] Moşoiu, "who was also the manager of
the high school (the Andrei Șaguna Romanian Orthodox high
school in Braşov) was known for his involvement in the
legionary activity (he was the Commander of one of its local
branches). After graduating from high school, I.G. joined the
Medico-Military Institute (Bucharest) and "Gabriel" went to
Prague. After 1948, they met again in Bucharest, on a daily
basis, since I.G. taught at the Institute of Hygiene.
Despite being rather ill (suffering from diabetes), I.G. was
very active, becoming a professor and the head of the Food
Hygiene Department (Bucharest Institute of Hygiene). He
was highly valued as a specialist, "Gabriel" convincingly using
the communist jargon of the time: he "combines theory with
practice and links laboratory research with practical
activities, such as supervising in bakeries, canteens, etc." He
had a vast journalistic activity, "Gabriel" citing in I.G.'s
defense his contributions to Scânteia and Economic Life
newspapers, ahead of the papers published in specialized
magazines…
Next came a significant detail: although generally he did not
have an active social life, I.G. celebrated his 60th birthday by
organizing a "comradely lunch at the Faculty of Military
Medicine". Among the guests featured professor [Nicolae]
Nestorescu, a microbiologist and immunologist (who also
was a former military physician) and lecturer Coman
Petrescu, PhD (a pediatrician dealing with rational child
nutrition). In "Gabriel"’s opinion, allegations that I.G. had
been involved in the legionary movement activities as a
student were simply "unfounded rumors."
However, in his Note, major I. Ion seemed keen to show his
superiors how cautious he was: "Since I.G. is known by the
Third Department (of the Securitate) as a former member of
the Iron Guard, the agent will have to inform us of any data
backing this assumption. In addition to that, the
correspondence with foreigners will be kept under
observation." Next came a list of names – French and
German researchers and professors from (Paris) and
(Heidelberg).
Here is what agent "Titi", who "kept him under observation
during his teaching activities”, wrote: "Always punctual,
having a commanding attitude, he teaches the students
notions of food hygiene during his two-hour lecture. During
his lectures he seems to speak with passion, having a
dignified attitude. From talking to other students, the source
found out that professor Gonţea is very demanding during
exams, asking the students to reproduce all the details, or
better said the whole lecture, word by word. He does not
hesitate to turn students out over the slightest mistake. His
behavior gives the impression of a modest man, deeply
involved in his profession."
Elly – a professional informer
In Iancu Ion Gonţea's file, there is a note received by
captainV. Ovidiu, on April 19, 1957, from agent "Elly",
reeking of antipathy towards I.G., a text in which one can
hardly tell the truth from "pure" lies. It is difficult, if not
downright impossible, to check these allegations because
the informer, hiding under the pseudonym given her by the
Securitate, seems to be a professional of delation, citing
people (giving their full names and the position held in the
Institute) who could allegedly back her allegations, but who
today, 60 years later, are most certainly dead...
"I inform you", wrote Elly, "that Dr. I.G., associate professor
of nutrition at the Faculty of Medicine, living at 244,
Dorobanti Street, phone 7.66.29, claims to be
«untouchable» because he is backed by Acad. Ștefan Milcu
and Acad. N. Lupu, who are «indebted» to him.
I.G. is the author of numerous fake public documents and
characterizations (within the IMF – Institute of Medicine and
Pharmacy), helped by former head of the personnel
department At.). All these facts are known by the
management. Dr. I. Per. from the Hygiene Institute,
Laboratory of Food Chemistry, 1, Leonte Street, can provide
82
references in this respect."
After this "introduction," "Elly" wrote that she knew I.G.
since November 1954. "I know that he was a legionary,
working in the cabinet of another Iron Guard physician, Dr.
Ru, within the Legionary Ethics Committee – at the time, the
steering committee of the Faculty of Medicine (?). At that
time he worked wearing a green, Iron Guard shirt; at Iron
Guard rallies he carried banners reading Nu merus nullus
(sic!) and Nu merus claus (sic!). prof.dr. I.I.N., manager of the
Institute of Physiology of the R.P.R. Academy, phone 4.20.59
(home) and Dr. Eug. D.), phone 7.31.16 (home) can give
references about his activity at the time. Among the acts of
hooliganism, I can mention the ones I heard about from Dr.
Eug. D., namely that Assoc. Prof. Dr. I.G., under the legionary
régime, tried to devastate the Cantacuzino Institute, kicking
the doors when he entered the rooms, destroying laboratory
equipment, etc. In the Military Sanitary Institute where he
worked for some time, the whole institute knew him as a
"passionate Iron Guard member" (Dr. Iac., Assistant at the
physiology department, tel. 3.27. 90 ,home, can give
references about this). In the bourgeois army, he was highly
regarded because of the wealth he still holds, to a great
extent:
- Mansion in Călimanesti
- Estate and mansion in Bran
- Houses in Bucharest
- Car etc.
Later on, Assoc. Prof. I.G. proved to be a hostile element,
pleading in favor of Antonescu's criminal actions against the
USSR. References: Dr. Eug. D. and Dr. P.
Thus, Assoc. Prof. Gonţea maintained ties with his former
collaborators from the Legionary Nest, Assoc. Prof. Pr. Gh.,
from the Physiology Department, with Tudor G., also from
the Physiology Department, with G. Maria from the same
department, about whom I will tell you in detail further
down. Assoc. Prof. I.G. has remained the same reactionary
person, nurturing sympathy for the Iron Guard, and still
indulging in hooliganism. Here are some facts:
1) He encourages the personnel not to apply for higher
positions since exams are "based on the Russian model and
have a temporary character". References can be given by C.
Adrian, assistant at the Physics Faculty, phone 2. 68.09
2) Assoc .prof. I.G. sent two articles for publication to the
Institute of Physiology of the Academy of the R.P.R. (People's
Republic of Romania), registered with no. 36 / 6.III.1957 of
the Nutrition Department:
- The bibliography of the first article includes 13 works, none
of them Soviet.
- The bibliography of the second article includes ten works,
all of them English and American.
- This amounts to hostile behavior towards Soviet science,
and within the department, which contrary to the ideological
orientation of the scientific research in the R.P.R.
3) He considers himself a "great patriot and a great
Romanian". Under this mask, Assoc. Prof. I.G. hides his
ferocious anti-semitism and hatred against elements
dedicated to the working class. References: 1. Gabriela from
Caritas, phone 2.90.40 who was an assistant at the
Department of Nutrition, Dr. D. Eugen, phone 7.31.16; M.
Maria. St. Constintin Street, No… Petre P. from the Cotroceni
Hygiene Institute.
4) Assoc. Prof. Gonţea Iancu (hereafter names were blacked
out by the CNSAS) – nurse G. Maria swore to me, in the
autumn of 1955, on the health of her child, that, as head of
the Nutrition Department, he had given her extra paid hours,
the equivalent of a part-time job, [but] from the date of
January 1, 1955 to September 1, 1955, he obliged her to give
him 1/2 of her part-time wage. G. Maria told me this out of
despair because (redacted by the CNSAS) his fabulous wealth
helped him back the interests of the Iron Guard. [And] after
she gave him this money, "which he literally grabbed from
her and which were part of her due", as a reward, assoc.prof.
Gonţea gave her the sack. The reason was another
subordinate, dr. Şuţescu Paraschiva (anonymized words by
the CNSAS) who [becoming a favorite] continued to work
with I.G. G.Maria told me all this on the way between
Ardealul Avenue and Plevnei Street, as she was going
towards Progresului to the Rectorate of the Institute of
Medicine and Pharmacy.
5) At the Nutrition Department, Assoc. Prof. Gonţea sells
overpriced wool and veal meat from his estate in Bran to the
staff, whom he obliges to buy, threatening to treat them
badly if they don't. Assist. A. C. can give references, phone
3.11.10.
6) (Anonymised paragraph by the CNSAS) G. Maria was a
notorious Iron Guard member, the daughter of the richest
merchant in Constanța who lived in the countryside in
Bulgaria until 1956, when she brought him back to Bucharest
for good since "rich people are no longer oppressed as they
used to be", according to her own words. G. Maria worked
with the Legionnaires, being... (redacted). Thus she helped
them set up camps in the V. Roaită resort and her father
helped by providing food and transportation.
7) As far as his behavior towards students is concerned, I can
mention that several of them have lodged complaints about
his demagogic manifestations with the Dean’s Office of the
Vol. CXXII • No. 2/2019 • August • Romanian Journal of Military Medicine
83
Faculty of Medicine, but to no avail. References can be given
by student P. Aurel from the sixth year. His attitude towards
the young employees of the Institute of Medicine and
Pharmacy has remained fierily reactionary and he is doing
his best to exclude those who had worked in ministries
representing our régime. I am attaching the original
statements by Prof. N., whom Assoc. Prof. Gonţea Iancu told
that he would do his best so that Dr. Maria Mih. and her
husband, C. Adrian, who had worked at the MAI [Ministry of
Internal Affairs ] would be sacked. C. Adrian was summoned
to the C.C. of the P.M.R. for a mission, which Gonţea branded
as a dangerous element for the reactionary clique he is a
member of. (I should mention that the summons took place
a few months after the appointment of assistant C. within
the Medicine Faculty).
8) About Assoc. Prof. Gonţea Iancu's son, whose name is
Gonţea Liviu, a fourth-year student at the Faculty of
Medicine, I know that he was under investigation by the
Ministry of Internal Affairs over hooliganism when he was a
high-school student. I mention that Gonţea Iancu was
connected to Lupaş Tudor, who provided him with articles
translated from Hungarian, which had been broadcasted on
the radio, which Gonţea Liviu handed to the students in his
group. In a conversation with Tudor Geor., Lupas's uncle,
who worked in the physiology laboratory, told me that «the
guilty people are free while his nephew is in prison.»
When I asked him if Gonţea’s son had been involved, he did
not give a straight answer, but made me understand that he
had."
(signed) Elly
We find ourselves in 1957, a few months after the Hungarian
revolution (called "counter-revolution" by the Communists),
when the vigilance and coercive measures of the Securitate
got a new "boost", stimulating the activity of informants.
Moreover, on October 27, 1956, in university cities, students
were out in the streets demanding an improvement in living
conditions, the removal of the Russian language from the
educational curricula, and the liberalization of social life,
demands which were followed by reprisals and arrests.
Students and professors thus becoming a target of the newly
established Ministry of State Security, an institution distinct
from the Ministry of Internal Affairs, at the time led by
Alexandru Draghici.
A year later, in June, a plenary session of the C.C. took place,
announcing a return to the struggle against bourgeois
ideology, criticism of intellectuals accused of snobbery,
cosmopolitanism, apoliticism, negativity etc. Thus, the
departure of the Soviet troops who had been stationed on
Romanian territory for 14 years, did not seem to be
auspicious to acts of dissent, especially from those who had
had certain political views in the past, even if they had let
themselves be carried away; on the contrary, it meant
increased vigilance8.
Ellyˊs denunciations were obviously not based on
"proletarian intransigence" or "ethical" reasons, but rather
on personal, vindictive motives, which, after so many years,
cannot be properly weighed. It is possible, however, that the
"witnesses" mentioned by the informer may have
considered themselves, for various reasons, harmed by the
teacher (possibly by the exigencies that he imposed) or
"stopped" in their desire for rapid ascension in the
professional field or on the social ladder. In that period, the
"weapon" at hand chosen by an informant in ensuring his
success was invoking an alleged Iron Guard activity, or at
least sympathy, on the part of the "target".
One of the graduates of the Faculty of Cluj (whose name was
blacked out), was "promoted", as early as his student years,
to a party activist, to the "Central Committee structure”!
Starting in 1949, he held important positions in the state
hierarchy: adviser to the minister of Health, then Sanitary
General Inspector. He became pro-rector of the Institute of
Medicine and Pharmacy in Bucharest (IMF) then, based on
this rapid ascension and, of course, "being a valuable
person", was named associate professor. (This rapid fast-
lane promotion took barely six years).Since 1955 he engaged
in research as head of department at the Hygiene and Public
Health Institute in Bucharest. How could "Elly” not cite his
name and indicate him as a credible witness in order to
assess professor Gonţea's activity and behavior?
And what about another rival, born in 1884? The latter
hoped that, thanks to the protection of his administrative
superiors and by "revealing" I.G.'s alleged "Legionnary
activity" and backing Elly's allegations, he could indefinitely
extend his teaching term, in no matter what department, if
Gonţea could be forced to give up the position he held
«based on merit».
Nevertheless, we should mention that Ellyˊs detailed
statements found in this file were not backed by any "notes"
or testimonies given by the witnesses she cited.
After August 23, 1944, the issue of the legionnaires had
become a major concern for the new power. In 1945, former
legionnaire’s members who were deemed as dangerous
were arrested and sent to labour camps. Others were to be
determined to become – and truly became – collaborators
of the Communist Party, following Ana Pauker's
intervention. On December 10, 1945, the Ministry of Internal
Affairs issued an order "legalizing" some of the former Iron
Guard members, who no longer posed a threat to the State
84
and who had offered their services to the new régime. It was
a bluff: the trio made up of Ana Pauker, Teohari Georgescu
(minister of Internal Affairs) and KGB general Nicolski were
later accused of having facilitated the infiltration of former
Iron Guard members into the Communist Party. As a
consequence, the three former Communist dignitaries were
ousted.
At that time, however, the Legionnary Movement ghost had
reappeared and informant "Elly" seized this opportunity to
accuse Iancu Gonţea. It is true that many intellectuals,
particularly younger ones, had sympathized with the
Legionnary Movement in the 1930s, even though they later
disavowed this affinity (see the notorious cases of Mircea
Eliade, Eugen Ionesco, Emil Cioran.) Many intellectuals from
the area of Braşov – Bran (eg, the great philologist Sextil
Puşcariu), shared rightist, or even Iron Guard sympathies, an
ideological confusion which they later regretted; among
them there were also many physicians who had acquired
some notoriety in their profession.
**
I once asked an older friend: why is there so much hatred
towards a man who, through his knowledge and hard work,
dedicated his life to medicine for the public welfare?
– "The he lazy man will throw stones only at the tree full of
fruit, so that he can collect the fallen fruit effortlessly", my
friend replied. "And then, we know from the Gospel that 'no
good tree will bear bad fruit, nor will a bad tree bear good
fruit.'"
References:
1. Stoian, Emil, „Portrete din Bran”, Dealul Medicilor Publishing
House, Braşov, 2002
2. Mihailide, Mihail, „Insolitul ospăț al unui devorator de arhive”,
Viaţa Medicală Românească Publishing House, 2017
3. Ibidem
4. Medicine History Documentary Library, National Institute for
Public Health, Bucharest, Iancu Gonţea File.
5. Ibidem
6. Ib. id. Reper 2
7. National Council for the Study of Security Structure Archives
(CNSAS), Central Archives Department, Operative file Gonţea Ion-
Iancu, cote 498910, vol.I and vol.II * The files were studied by 10
other people between April 5, 1969 and March 3, 1976).
8. Collective, coordinator Valentina Bilcea, „Istoria românilor.
Date Fapte. Oarneni”; Foreword: Professor Adrian Cioroianu Ph.D.,
Meronia Publishing House, Bucharest, 2018
Vol. CXXII • No. 2/2019 • August • Romanian Journal of Military Medicine
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ADMINISTRATIVE ISSUES
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Thank you for your interest in Romanian Journal of Military Medicine. Please read the complete Author Guidelines carefully prior to submission, including the section on copyright. To ensure fast peer review and publication, manuscripts that do not adhere to the following instructions will be returned to the corresponding author for technical revision before undergoing peer review. Note that submission implies that the content has not been published or submitted for publication elsewhere except as a brief abstract in the proceedings of a scientific meeting or symposium. Once you have prepared your submission in accordance with the Guidelines, manuscripts should be submitted online at [email protected]. We look forward to your submission.
EDITORIAL AND CONTENT CONSIDERATIONS Aims and Scope Romanian Journal of Military Medicine (RJMM) is the official journal of the Romanian Association of Military Physicians and Pharmacists. The Journal publishes peer-reviewed original papers, reviews, meta-analyses and systematic reviews, and editorials concerned with clinical practice and research in the fields of medicine. Papers cover the medical, surgical, radiological, pathological, biochemical, physiological, ethical and historical aspects of the subject areas. Clinical trials are afforded expedited publication if deemed suitable. RJMM also deals with the basic sciences and experimental work, particularly that with a clear relevance to disease mechanisms and new therapies. Case reports and letters to the Editor will not be considered for publication.
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86
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Romanian Journal of Military Medicine
New Series, Vol. CXXII, No 2/2019, August
ISSN-L 1222-5126; eISSN 2501-2312; pISSN 1222-5126