conservative treatment of the acute and complicated ... · pathophysiologie. kessler:...

Klinik und Poliklinik für Kinderchirurgie

Universitätsklinik für Kinderchirurgie

Conservative treatment of the acute and

complicated appendicitis

U. Kessler

Kessler: Blinddarmentzündung 2




«The history of appendicitis is an excellent

anecdote for the history of surgery itself»

https://upload.wikimedia.org/wikipedia/commons/4/49/Wachstumsmodelle.png

Streck and Maxwell, Ann Surg 2014



Paleopathology

www.theboltonnews.co.uk

‘…a thick band of old

adhesion springs from the

appendix near its tip and

passes over to be attached to

the other side of the pelvis. It

seems to be clear evidence of

old appendicitis.’

Smith GE. Anatomical report. The archæological survey of

Nubia. Cairo: National Printing Department, 1908



Ägypten - Mittelalter



Mittelalter: Die « Seitenkrankheit »

11. Jahrhundert … Rob ist besessen davon, die menschliche Anatomie präziser zu

studieren. Ein Konflikt entzündet sich an der ethischen Beurteilung der Obduktion

am menschlichen Leichnam, da sie von den Religionen streng verboten ist. Von

einem an der Seitenkrankheit dahinscheidenden Zoroastrier erfährt Rob, dass in

dessen Religion der verstorbene Körper nicht intakt bleiben müsse. Heimlich führt

Rob bei ihm eine Obduktion durch, wobei er den entzündeten Wurmfortsatz als

Todesursache entdeckt. Allerdings werden seine Forschungen entdeckt, er und

sein Meister verraten und vor dem Gericht der Mullahs zum Tode verurteilt. Später

kann er beim Schah eine Blinddarmoperation unter Betäubung durchführen: Die

Seitenkrankheit wird besiegt.

…

Zum Dank für die gelungene Operation verhilft der Schah vielen Juden unter Robs

Führung zur Flucht aus der Stadt. Er und Rebecca, die …….

Der Medicus, Roman Noah Gordon, Film- Regie Philip Stölzl 2013 in Babelsberg

?



Erste Darstellungen

Wiliams and Wilkins, Baltimore

Leonardo da Vinci 1492

«Caecum», Berengario

da Carpi, Andreas

Vesalius 1543

De Humanis Corporis Fabrica, History of Science

Collections, University of Oklahoma Libraries

«Wurm»,

Fallopius 1561

Hall of Faculty of Medicine

and Surgery in Palazzo Bo, University of Padua



Krankheitsbild:

Verwirrung im rechten Unterbauch

«Perforation durch

Fremdkörper»

Heister 1709

Mestivier 1759

Amyand 1735

«Dünndarm-

Pathologie»

Boerhaave 1709

«Caecum- Pathologie:

Perityphlitis»

Dupuytren/ Goldbeck

1830

τυφλος, typhlos, blind



Maximale Therapie bis Mitte des 19. JH

In 1876 I broke down with a serious illness, which was diagnosed as perityphlitis, but which I

now know was appendicitis. Dr. Reginald Fitz had not opened the eyes of the profession to

this disease with his classical paper, nor had Dr. Simon Baruch, a leader in medicine, yet laid

mankind under never-ending obligation by his recognition of and insistence upon the

necessity of immediate operation. The only operation in my case was the insertion of an

exploring needle through the abdominal wall deeply into the indurated mass, a procedure

more dangerous than operation, and by no means painless. No suppuration was discovered,

and at the end of two weeks the abscess discharged into the cæcum. Here followed a slow

convalescence, …

New York Polyclinic Graduate Medical

School and Hospital

http://www.encyclopediaofalabama.org/article/m-8186



Synthese von klinischem Krankheitsbild

und der zugrunde liegenden Pathologie

• Parkinson 1812

Med Chir Trans. 1812;3:57-8.

Case of diseased Appendix Vermiformis.

• Fitz 1886



19. JH: Fortschritte in der Medizin:

Anästhesie und Asepsie

William T.G. Morton 1846: Aether, NO



19. JH: Asepsie: Louis Pasteur 1878

La théorie des germes et ses applications à la médecine et à la

chirurgie », Bulletin de l'Académie de médecine, 2e série, t. 7, 1878



19. JH: Asepsie: Lister 1867, Semmelweis



19. JH: Asepsie: Semmelweis

Der « Semmelweis – Reflex »

J Hist Med Allied Sci (1979) XXXIV (3): 255-272



Synthese von Klinik, Pathologie und

«modernen Mitteln» -> Therapie

Treves 1886, Morton 1887, McBurney 1889

Ann SurgAnn Surg



20. JH: Fortschritte in der Medizin

Antibiotika

Intravenöse

Zugänge

Labor &

Bildgebung:

Epidemiologie,

«evidence based

medicine»

Chirurgische

Technik

Pathophysiologie



Gründe von Bauchschmerz

(Notfallvorstellung im Spital, 2-16 Jahre)

Diagnose n %

« Bauchschmerzen » 135 36

Gastroenteritis 62 16

Appendizitis 29 8

Verstopfung 27 7

Harnwegsinfektion 22 6

Viraler Infekt 11 3

Streptokokken

Pharyngitis

10 3

Sonst. Pharyngitis 10 3

Pneumonie 6 2

Otitis 6 2

Reynolds, Pediatr Emerg Care, 1992



Häufigkeit je nach Alter

Al-Omran et al, Can J Surg 2003



Papandria et al, J Surg Res 2013

Perforation je nach Alter

30%

20%

10%

0%



•Subjektiv : douleur en FID

douleur migrante

•Objektiv: défense abdominale

douleur à la détente

•Assessment: Labor: Leucocytose

CRP

Urin

• Bildgebung: US

CT / IRM

( -> PROCEDERE)

Diagnosestellung: SOAP

http://www.google.ch/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&cad=rja&uact=8&docid=HXg-SaIx8JBwkM&tbnid=sW2dvBpMJqwRMM:&ved=0CAcQjRw&url=http%3A%2F%2Fwww.bigg.hu%2Fbabamama%2Ftag%2Fbetegsegek%2F&ei=Sww4VIKlMuTV7gaEyIDICg&bvm=bv.77161500,d.ZGU&psig=AFQjCNHaHiR0wzGCWMlF8ng_i9MvhXdxPw&ust=1413045674436840



Samuel, J Pediatr Surg 2002

Diagnostik- Schema bei Kindern (uptodate)



Diagnostik bei Kindern

Ultraschall

• 1. Wahl, hoher PPV, Untersucher- abhängig

• Bei unklarem/ negativem und nicht mit klinischem Befund

übereinstimmenden Befund:

–Beobachten und oder US Wiederholen

–CT oder MRT anschliessen

Garcia Pena, JAMA 1999

US



CTErstellung einer alternativen Diagnose

bei 62/ 199 Kindern mit negativem

Resultat für Appendizitis

Mullins et al, AJR 2001 Brenner et al, NEJM 2007



CT versus US

Bachur et al Ann Emerg Med 2012



Therapie: Gold-standard Appendektomie



Laparoskopische Appendektomie

• Less wound infections (OR 0.20)

• Less pain

• Reduction in hospital stay (1d)

• Longer operation time (6 to 16min)

Sauerland et al Cochrane Analysis 2010



20. JH: Antibiotika

The Nobel Prize in Physiology or Medicine 1945 was awarded jointly to Sir

Alexander Fleming, Ernst Boris Chain and Sir Howard Walter Florey "for

the discovery of penicillin and its curative effect in various infectious

diseases".



1956, Eric Coldrey, first

publication in the British

Medical Journal:

1908, Alfred Stengel: “Treated in a

purely medical or tentative

manner, the great majority of

patients with appendicitis recover”

20. JH: Antibiotika



< 30 d

> 30 d

McCutcheon et al, Journal of the American College of Surgeons, 2014

Retrospective analysis of outcome in adults with

non-complicated appendicitis



Randomised trials comparing antibiotics with

appendicectomy in adults (non-complicated)Eriksson, Br J Surg 1995 Styrud, World J Surg 2006 Hansson, Br J Surg 2009 Vons, Lancet 2011 Salminen, JAMA 2015

Appendicitis Non-complicated Non-complicated Non-complicated Non-complicated (CT)Non-complicated, no

appenicolith (CT)

Antibiotic

2j iv: Cefotaxim 2x2g/d &

Tinidazol 0.8g/d,

8j p.os: Ofloxacin 2x 200mg/d

& Tinidazole 2x400mg/d

2j iv: Cefotaxim 2x2g/d &

Tinidazol 0.8g/d,

10j p.os: Ofloxacin 2x 200mg/d

& Tinidazole 2x400mg/d

1-2j: Cefotaxim 2x1g/d &

Metronidazole 1x1.5g/d,

10j p.os: Ciprofloxacin 2x

500mg/d & Metronidazole 3x

400mg/d

0-2j iv: CoAmoxi 3x1g

8-15j p.os: CoAmoxi 3x1g

3d iv: Ertapeneme 1g/d

7d p.os: Levofloxacin 500mg

1x/d & Metronidazole

3x500mg/d

Number of patients in

antibiotic group20 128 202 120 256

Failure If symptoms persist> 24h Surgeons/ patients decisionIf symptoms persist> 48h,

or present at d 8, 15, or 30

Surgery for appendicitis

within 1 year

Antibiotic failure

needing

appendicectomy

1 (5%) 15 (12%) 105 (52%) 14 (12%) 15 (6%)

Normal appendix ,

failure0 1 3 1 0

Follow- up 1 year 1 year 1 year 1 year 1 year

Recurrence requiring

appendicectomy7 (35%) 16 (13%) 11 (5%) 30 (25%) 55 (21%)

Normal appendix,

recurrence0 0 0 4 5

Did not need

appendicectomy13/20 (65%) 98/128 (77%) 89/202 (44%) 81/120 (68%) 186/ 256 (73%)



Trials comparing antibiotics with appendectomy

in children (non- complicated)

Koike, J Pediatr Surg 2014 Minneci, J Am Coll Surg 2014 Svensson, Ann Surg 2015 Hartwich, J Pediatr Surg 2015

Appendicitis Non-complicated (US or CT)Non-complicated (US or CT), no

fecolithNon-complicated (US or CT) Non-complicated (US or MRI)

Antibiotic2d iv: Cefoperazone 3x20mg/kg/d

3d p.os: Cefcabene Pivoxil (dose?)

1d-.. iv: Piperacilline/ Tazobactame or

Ciprofloxacine/ Metronidazole,

..- 10j (total) p.os: Amoxicilline/

clavulanic acid or Ciprofloxacine/

Metronidazole

2d- …iv: Meronem 3x10mg/kg/d &

Metronidazole 1x20mg/kg/d,

8d p.os: Ciprofloxacin 2x 20mg/kg/d

& Metronidazole 1x 20mg/kg/d

1d: 1d-.. iv: Piperacilline/

Tazobactame 2x 100mg/kg

2d-…: Amoxicilline/ clavulanic acid

50mg/kg/d

Setting Retrospective ProspectiveProspective randomized

controlled

Age 1- 15y 7- 17 5- 15 5- 18

Number of patients in

antibiotic group130 30 24 24

Failure ?Lack of clinical improvement within

24h

Lack of improvement and

surgeons/ parents decision

Lack of clinical improvement

within 8h

Antibiotic failure needing

appendectomy5 (4%) 2 (7%) 2 (10%) 3 (12.5%)

Normal appendix , failure ? ? 1 [and 1 perf] 1

Follow- up 1.5- 3 years 30d 1 year 14 mo

Recurrence requiring

appendicectomy24/125 (19%) 1 (3%) 1 (5%) [but 6 parental wish] 2 (9.5%) [but 2 parental wish]

Normal appendix,

recurrence? 0 6 2

Did not need

appendicectomy101/130 (78%) 27/30 (90%) 15/24 (62%) 17/24 (71%)



Kessler U et al Arch Dis Child 2017

Trials comparing antibiotics with appendectomy in

children (non- complicated) (n=424)

Complications



Kessler U et al Arch Dis Child 2017

Trials comparing antibiotics with appendectomy in

children (non- complicated) (n=424)

Efficacy



Treatment for complicated appendicitis in

children (n=1243)

Vaos et al J Pediatr Surg 2018

Complications



Treatment for complicated appendicitis in

children (n=1243)

Vaos et al J Pediatr Surg 2018

Length of stay



• Surgery remains the gold standard

• There might be a place for conservative treatment in

both complicated and uncomplicated appendicitis

• ? Interval appendectomy

• ? Do we need the appendix

• ? Pathophysiological mechanisms of inflammation of

the appendix

• ? Reason for non- response to antibiotics

Conclusion on the treatment of

acute appendicits



Physiologie:

«Sinnloses entwicklungsgeschichtliches Ueberbleibsel»

Ch. Darwin 1871



Physiologie

• «Delayed accumulation of IgA+ cells in the large intestine

in appendectomized mice»

Masahata et al, Nature Communications 2014

• «2.5fold increased risk of recurrent C. difficile colitis in

appendectomized patients»

Im et al, Clin Gastroenterol Hepatol 2011

• «The appendix is a potential source of autologous neural

stem cells for the Gitract»

Zakhem et al, Stemm Cells Translational Medicine 2015



Physiologie

• «1.6 fold increased risk of developing Crohn’s disease

after appendectomy»

Kaplan et al, Am J Gastroenterol 2008

• «Appendectomy ameliorates intestinal inflammation in

IBD»

Krieglstein et al, J Surg Res 2001

Mizoguchi et al, J Exp Med 1996

• «1.5 fold increased risk of developing new DM II after

appendectomy»

Wei et al, BJS 2015



Physiologie



«The safe house for bacteria»

World Journal Gastroenterology

2013



Genetischer «Background» der Appendizitis



Livingston et al, Ann Surg 2007

Perforation der Appendix – unterschiedliche

Pathologie?

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