Small Intestine Tumours

8/6/2019 Small Intestine Tumours

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SMALL INTESTINE TUMOURS

MANAGEMENT


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INVESTIGATIONS

PATHOLOGICAL CLASSIFICATION

STAGING TREATEMENT OPTIONS


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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


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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%


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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


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Small bowel endoscopy

push enteroscopy

intraoperative or laparoscopically assisted

enteroscopy double-balloon enteroscopy


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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


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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


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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


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Double ballon enteroscopy


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capsule endoscopy


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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).


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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


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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


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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


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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


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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


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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%


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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


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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


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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


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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.


19971997

66%66% 30%30% 77 2323

Talamonti et al.Talamonti et al.

Archives of SurgeryArchives of Surgery

2002200262%62% 37%37% 99 4040


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Prognosis

Poor prognosis correlated with:

Mural penetration

Nodal involvement

Distant metastasis

Perineural involvement

Large tumor size

Poor histologic grade


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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


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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


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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


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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)


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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


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GISTs of the small intestine


DuodenumDuodenum





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%


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GISTs of the small intestine


DuodenumDuodenum





19971997

75%75% 25%25% 25%25% 12.5%12.5% 0%0% 63.5%63.5%


2002200280%80% 20%20% 12%12% 20%20% 48%48% 20%20%


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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


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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


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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


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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


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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


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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


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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


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Carcinoid tumors of the small intestine


DuodenumDuodenum





19971997

28%28% 72%72% 11%11% 0%0% 22%22% 66%66%


2002200222%22% 78%78% 8%8% 24%24% 38%38% 30%30%


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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


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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


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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


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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

Small Intestine Tumours

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