small intestine tumours
TRANSCRIPT
-
8/6/2019 Small Intestine Tumours
1/48
SMALL INTESTINE TUMOURS
MANAGEMENT
-
8/6/2019 Small Intestine Tumours
2/48
INVESTIGATIONS
PATHOLOGICAL CLASSIFICATION
STAGING TREATEMENT OPTIONS
-
8/6/2019 Small Intestine Tumours
3/48
PLAIN X RAY ABDOMEN
1. Plain X ray Abdomen : useful for
demonstration of obstructions and
displacement of bowel by mass. more useful only in advanced cases
Not much use in early stage diseases
-
8/6/2019 Small Intestine Tumours
4/48
Small bowel follow-through
Noninvasive and relatively inexpensive
Often insensitive
Small bowel follow-through is still the mostcommonly used method in most institutions in
the evaluation of small bowel disease
sensitivity for small bowel tumours only 33%
-
8/6/2019 Small Intestine Tumours
5/48
Enteroclysis
more sensitive procedure is the double-contrastmodality of enteroclysis
which involves placing a nasogastric tube intothe descending duodenum and infusing bariumand methylcellulose under pressure.
enables better visualization of the intestinal
lumen and mucosal surface, and has a 90%sensitivity for small bowel tumours
-
8/6/2019 Small Intestine Tumours
6/48
-
8/6/2019 Small Intestine Tumours
7/48
Small bowel endoscopy
push enteroscopy
intraoperative or laparoscopically assisted
enteroscopy double-balloon enteroscopy
-
8/6/2019 Small Intestine Tumours
8/48
Push enteroscopy
Push enteroscopy involves an intestinal
intubation of a 220- to 250-cm instrument,
usually with fluoroscopic assistance, and can
be used to examine the jejunum for mean
lengths of 120 cm beyond the ligament of
Treitz
-
8/6/2019 Small Intestine Tumours
9/48
Intra operative endoscopy
During intraoperative endoscopy, the surgeon manuallymanipulates through the small bowel wall with either apush endoscope (anterograde) or a colonoscope
(retrograde) to examine the entire small bowel. The surgeon can mark the lesions of interest, usually by
suture, and resect at the completion of the enteroscopy.
This invasive diagnostic and therapeutic technique isuseful in cases of multiple lesions, such as in PJsyndrome and when other modalities have failed indiagnosis
-
8/6/2019 Small Intestine Tumours
10/48
Double ballon enteroscopy
In double-balloon enteroscopy, an endoscope anda soft flexible overtube, each of which has aninflatable balloon attached to its distal end, areemployed together.
The two tubes are advanced over one anotherrepeatedly using alternating inflation of theballoons to hold position, allowing deepadvancement into the small intestine.
The entire small intestine can be examined usingthis method with less discomfort than experiencedwith the push method
-
8/6/2019 Small Intestine Tumours
11/48
Double ballon enteroscopy
-
8/6/2019 Small Intestine Tumours
12/48
capsule endoscopy
-
8/6/2019 Small Intestine Tumours
13/48
capsule endoscopy was more effective in detecting
small tumors in the small intestine than traditional
modalities
lack of forward and backward movement to examine
an area of interest, inability to use instruments to
carry out biopsy or treatment, reliance on a good
bowel prep and inadequate image resolution
The main indication for capsule endoscopy remains
occult gastrointestinal bleeding (OGIB).
-
8/6/2019 Small Intestine Tumours
14/48
Endoscopic ultrasonography (EUS)
used to detect and stage small bowel tumors
and allows real-time interventional diagnostic
procedures
mainly in the periampullary region
EUS has been shown to be superior to CT and
magnetic resonance imaging (MRI) in
predicting vascular invasion and overall
assessment of T stage of ampullary neoplasms
-
8/6/2019 Small Intestine Tumours
15/48
Computed Tomography Enteroclysis
it utilizes water rather than oral hypaque-basedcontrast,
it utilizes the thinner collimation possible with
modern 64 and 128 multidetector CT scannersto quickly image large sections of the
mesenteric small bowel
The overall sensitivity and specificity in
identifying patients with small bowel lesions
were 84.7% and 96.9%, respectively
-
8/6/2019 Small Intestine Tumours
16/48
-
8/6/2019 Small Intestine Tumours
17/48
PRIMARYTUMOR (T)
TX Primary tumor cannot be assessed
T0 No evidence of primary tumor
TIS Carcinoma in situ
T1 Tumor invades lamina propria or submucosa
T2 Tumor invades muscularis propria
T3 Tumor invades through the muscularis propria into the subserosa or into thenonperitonealized perimuscular tissue (mesentery or retroperitoneum) withextension 2 cm or less
T4 Tumor perforates the visceral peritoneum or directly invades other organs orstructures (includes other loops of small intestine, mesentery, or retroperitoneummore than 2 cm, and abdominal wall by way of serosa; for duodenum only,invasion of pancreas)
REGIONAL LYMPHNODES (N)
NX Regional lymph nodes cannot be assessed
N0 No regional lymph node metastasis
N1 Regional lymph node metastasis
DISTANT METASTASIS (M)
MX Distant metastasis cannot be assessed
M0 No distant metastasis
Ml Distant metastasis
-
8/6/2019 Small Intestine Tumours
18/48
Stage Criteria
I Involvement of a single nodal group (1) or a single extralymphatic
organ or site (IE)
II Involvement of more than one nodal group on the same side of
the diaphragm (II) or a single extralymphatic site with one or
more nodal groups on the same side of the diaphragm (IIE)
III Involvement of nodes on both sides of the diaphragm (III) with or
without involvement of extralymphatic sites (IIIE), spleen (IIIS), or
both (IIIES)
IV Diffuse involvement of viscera or bone marrow
Ann Arbor Staging System for Small Bowel Lymphoma
-
8/6/2019 Small Intestine Tumours
19/48
familial polyposis, chemoprevention with sulindacor cyclo-oxygenase-2 inhibitors may be beneficial
30-50% are adenocarcinomas
25-30% are carcinoids
15-20% are lymphomas
10-20% are gastrointestinal stromal tumors
-
8/6/2019 Small Intestine Tumours
20/48
Adenocarcinoma of the small intestine
StudyStudy LocationLocation Stage at presentationStage at presentation
DuodenumDuodenum
and jejunumand jejunum
IleumIleum II IIII IIIIII IVIV
Cunningham etCunningham etal.al.
Annals of SurgeryAnnals of Surgery
19971997
79%79% 21%21% 6.9%6.9% 24%24% 24%24% 45%45%
Talamonti etTalamonti etal.al.
Archives of SurgeryArchives of Surgery
20022002
76%76% 24%24% 4.8%4.8% 19%19% 38%38% 38%38%
-
8/6/2019 Small Intestine Tumours
21/48
Adenocarcinoma and therapy
Surgery is the treatment of choice Procedure of choice is determined by location of tumor:
1st and 2ndportion of the duodenum
pancreaticoduodenectomy
Distal duodenum resection and duodenojejunostomy
Jejunum and ileum segmental resection includingwide mesentery resection (6 inches)
Terminal ileum right hemicolectomy
-
8/6/2019 Small Intestine Tumours
22/48
Surgical pearls
Resection of adequate mesentery is often limited byproximity of nodes or tumor to the SMA
Margin-status must be confirmed by frozen-section ifin question
Patients with metastatic disease should undergo
resection in most cases to prevent later complications
-
8/6/2019 Small Intestine Tumours
23/48
Adjuvant therapy
Patients who undergo radical surgery often later diefrom distant disease recurrence
No proven survival benefit
No prospective studies
5-fluorouracil has shown the most promise
-
8/6/2019 Small Intestine Tumours
24/48
-
8/6/2019 Small Intestine Tumours
25/48
Prognosis
StudyStudy CurativeCurative
resectionresection
raterate
Overall 5Overall 5
yearyear
survivalsurvival
Median survival timeMedian survival time
(months)(months)
NoncurativeNoncurative
resectionresection
CurativeCurative
resectionresectionCunningham etCunningham et
al.al.
Annals of SurgeryAnnals of Surgery
19971997
66%66% 30%30% 77 2323
Talamonti et al.Talamonti et al.
Archives of SurgeryArchives of Surgery
2002200262%62% 37%37% 99 4040
-
8/6/2019 Small Intestine Tumours
26/48
Prognosis
Poor prognosis correlated with:
Mural penetration
Nodal involvement
Distant metastasis
Perineural involvement
Large tumor size
Poor histologic grade
-
8/6/2019 Small Intestine Tumours
27/48
Metastatic disease involving small bowel
Secondary neoplastic involvement of small intestine
is more frequent than primary small bowel neoplasia
Primary tumors of the colon, ovary, uterus, and
stomach typically involve the colon by direct
invasion or intraperitoneal spread
Primary tumors from breast, lung, and melanoma
metastasize to small bowel hematogenously
-
8/6/2019 Small Intestine Tumours
28/48
Metastatic disease involving small bowel
Treatment is palliative
Limited resection
Intestinal bypass
Palliative Rt for bleeding and obstruction
Melanoma
Metastatic focus may further disseminate to small
bowel mesentery and draining lymph nodes Aggressive resection may improve disease-free
survival
-
8/6/2019 Small Intestine Tumours
29/48
Gastrointestinal stromal tumors
Visceral sarcomas, previously classified asleiyomyomas and leiyomyosarcomas
Now classified as GISTs with a range of biological
behaviors from low grade to high grade malignancies
Traditionally, microscopic findings were used todefine malignancy including:
Increased cell size Increased cell irregularity
Lack of cell differentiation
Presence of cells with hyperchromic and multiple nuclei
-
8/6/2019 Small Intestine Tumours
30/48
-
8/6/2019 Small Intestine Tumours
31/48
GISTs Tumor biology
Proposed to arise from the interstitial cell of Cajal, anintestinal pacemaker cell of mesodermal origin
Similar cell markers to those of normal Cajal cells
1) myeloid stem cell antigen CD34
2) KIT receptor tyrosine kinase3) variably positive for smooth-muscle actin
4) usually negative for desmin
Previously thought to be smooth muscle neoplasms but now
accepted to have:1) myogenic features (smooth muscle GIST)
2) neural features (GI autonomic nerve tumor)
3) myogenic and neural features (mixed GIST)
-
8/6/2019 Small Intestine Tumours
32/48
Clinical features of GISTs
Most commonly present with pain and weight loss
Most commonly present in the 6th and 7th decades butmay occur at any age
Distribution of occurrence is proportional to thelength of the segments of the small bowel
Lesions occur in extraluminal, subserosal locations
Often develop central ischemia and necrosis thatleads to bleeding
-
8/6/2019 Small Intestine Tumours
33/48
GISTs of the small intestine
StudyStudy LocationLocation Stage at presentationStage at presentation
DuodenumDuodenum
and jejunumand jejunum
IleumIleum II IIII IIIIII IVIV
Cunningham etCunningham etal.al.
Annals of SurgeryAnnals of Surgery
19971997
75%75% 25%25% 25%25% 12.5%12.5% 0%0% 63.5%63.5%
Talamonti et al.Talamonti et al.Archives of SurgeryArchives of Surgery
2002200280%80% 20%20% 12%12% 20%20% 48%48% 20%20%
-
8/6/2019 Small Intestine Tumours
34/48
GISTs of the small intestine
StudyStudy LocationLocation Stage at presentationStage at presentation
DuodenumDuodenum
and jejunumand jejunum
IleumIleum II IIII IIIIII IVIV
Cunningham etCunningham etal.al.
Annals of SurgeryAnnals of Surgery
19971997
75%75% 25%25% 25%25% 12.5%12.5% 0%0% 63.5%63.5%
Talamonti et al.Talamonti et al.Archives of SurgeryArchives of Surgery
2002200280%80% 20%20% 12%12% 20%20% 48%48% 20%20%
-
8/6/2019 Small Intestine Tumours
35/48
Prognostic factors and therapy of GISTs
Only complete resection has been found to be asignificant favorable prognostic factor
Surgical resection is therefore the mainstay of therapyand should include any involved adjacent organs Complete resection results in 3 and 5-year survival rates of 54% and
42% compared to 13% and 9% after incomplete resection
No added benefit to wide resections or extensivelymphadenectomies
-
8/6/2019 Small Intestine Tumours
36/48
Prognostic factors and therapy of GISTs
Poor prognostic factors include tumors greater than 5cm, non-smooth muscle cell differentiation, and those
classified as high grade
Metastases present in 30%; most commonly hepatic
Recurrence rates of 25-50% reported
No demonstrable benefit of adjuvant therapy
-
8/6/2019 Small Intestine Tumours
37/48
GISTs and STI-571 Molecular therapeutic options
Most GISTs (52-85%) have a gain-of-functionmutation in the c-kit proto-oncogene
Results in ligand-independent activation of the KITreceptor tyrosine kinase
Unopposed stimulus for cell growth
STI-571
molecule which inhibits:
Enzymatic activity of the KIT tyrosine kinases,
Platelet-derived growth factor receptor
BCR-ABL fusion protein
-
8/6/2019 Small Intestine Tumours
38/48
GISTs and STI-571 Molecular therapeutic options
Initial phase II trial of STI-571 in patients with metastatic
GISTs (follow-up of three months)
Partial response rate in 59%
Stable disease in 27%
Progression of disease in 13%
86% had a mutation in c-kit and were more likely to respond
EORTC study showed similar results
Partial response rate in 69%
Stable disease in 19%
Progression of disease in 11%
Dematteo et al. Human Pathology. May 2002
-
8/6/2019 Small Intestine Tumours
39/48
-
8/6/2019 Small Intestine Tumours
40/48
Clinical features of carcinoid tumors
Most commonly present in the 7th decade
Often present with nonspecific complaints
Up to 50% of patients present with obstruction
Carcinoid syndrome, marked by flushing and diarrhea, is rareand occurs in only 5-7% of patients
Right sided valvular fibrosis occurs late in the disease
Increasing frequency from the duodenum to the ileum
-
8/6/2019 Small Intestine Tumours
41/48
Pathological features of carcinoid tumors
Carcinoid invasion into the mesentery leads to
fibrosis and often kinking of the small intestine
Thickening of the vessel wall is also present and maylead to ischemic changes in the gut
Serotonin is postulated to be responsible for these
features
-
8/6/2019 Small Intestine Tumours
42/48
Diagnosis of Carcinoid Tumors
Traditional studies may fail to demonstrate theprimary tumor
Indium-labeled octreotide scan is the most accurate(sensitivity of 90%) means of localizing a carcinoidtumor Tumor cells express somatostatin receptors which take up
octreotide
24-hour urine levels of 5-hydroxyindoleacetic acid(5-HIAA) may alone be diagnostic Serotonin is metabolized in the liver to 5-HIAA and
excreted in the urine
-
8/6/2019 Small Intestine Tumours
43/48
Carcinoid tumors of the small intestine
StudyStudy LocationLocation Stage at presentationStage at presentation
DuodenumDuodenum
and jejunumand jejunum
IleumIleum II IIII IIIIII IVIV
Cunningham etCunningham etal.al.
Annals of SurgeryAnnals of Surgery
19971997
28%28% 72%72% 11%11% 0%0% 22%22% 66%66%
Talamonti et al.Talamonti et al.Archives of SurgeryArchives of Surgery
2002200222%22% 78%78% 8%8% 24%24% 38%38% 30%30%
-
8/6/2019 Small Intestine Tumours
44/48
-
8/6/2019 Small Intestine Tumours
45/48
Surgical therapy of carcinoid tumors
Surgical excision is the mainstay of therapy
Isolated disease is widely resected
Synchronous tumors are found in 33-40% of patients
and should all be excised if feasible
Noncarcinoid synchronous tumors are found in up to
25% of patients Typically tumors of the breast, lung, stomach, or colon
-
8/6/2019 Small Intestine Tumours
46/48
Surgical therapy of carcinoid tumors
Tumor size is an unreliable predictor of metastaticdisease
Aggressive attempts should be made to resectmetastatic disease
Decreases the need for medical therapy Prolongs survival
Hepatic metastases
Surgical resection Hepatic artery embolization
Cryosugery
Radiofrequency ablation
Transplantation
-
8/6/2019 Small Intestine Tumours
47/48
Medical therapy of small bowel carcinoid tumors
Octreotide inhibits tumor secretion of hormones
May have a direct tumor control effect on carcinoid tumors
Relieves flushing in 76% of patients
Improves diarrhea in 83%
Decreases the urinary 5-HIAA levels in 80%
Interferes with endo-and exocrine pancreas function
-
8/6/2019 Small Intestine Tumours
48/48
Medical therapy of small bowel carcinoid tumors
Interferon-alpha has shown improvement in
symptoms in 68% and a biochemical response in 42%
Use limited by high incidence of side effects
Response to chemotherapy has been variable and
short lived
Combination of streptozocin and 5-fluorouracil has shown
a 20-30% response rate
No proven benefit of radiotherapy