powerpoint: lecture 10, the small bowel and appendix

THE SMALL BOWEL AND THE SMALL BOWEL AND APPENDIXAPPENDIX

ANATOMY SMALL BOWELANATOMY SMALL BOWEL

Three regions: duodenum, jejunum and Three regions: duodenum, jejunum and ileumileum

Duodenum- deeply placed ,C-shaped, Duodenum- deeply placed ,C-shaped, receives bile and pancreatic juice through receives bile and pancreatic juice through Vater ampulla- D2Vater ampulla- D2

Jejunum- upper left part of the abdo. cavityJejunum- upper left part of the abdo. cavity

Ileum- lower right part of the abdominal Ileum- lower right part of the abdominal and pelvic cavityand pelvic cavity

6 m small bowel6 m small bowel2/5 jejunum, 3/5 ileum2/5 jejunum, 3/5 ileum

ANATOMY SMALL BOWELANATOMY SMALL BOWEL

Jejunum is larger in diameter, thicker Jejunum is larger in diameter, thicker walled, more prominent mucosal foldswalled, more prominent mucosal folds

Arterial supply – branches of the SMAArterial supply – branches of the SMA

Absorbtion area of the nutrients- 500 m2Absorbtion area of the nutrients- 500 m2

Submucosa is the strongest layer, Submucosa is the strongest layer, provides strength to an intestinal provides strength to an intestinal anastomosisanastomosis

PHYSIOLOGY SMALL BOWELPHYSIOLOGY SMALL BOWEL

The primary functions: digestion and The primary functions: digestion and absorbtionabsorbtion

All ingested food and fluid and secretions All ingested food and fluid and secretions from the stomach, liver, pancreas reach from the stomach, liver, pancreas reach the small bowel- total volume- 9 l /day and the small bowel- total volume- 9 l /day and all but 1-2l will be absorbedall but 1-2l will be absorbed

PHYSIOLOGY SMALL BOWELPHYSIOLOGY SMALL BOWEL

Motility- two types of contractions Motility- two types of contractions

To-and-froTo-and-fro motion mixes chyme with motion mixes chyme with digestive juices for prolonged exposure to digestive juices for prolonged exposure to the absorbative mucosathe absorbative mucosa

PeristalticPeristaltic contractions move food distally contractions move food distally

PNS- contractions, SNS- relaxationPNS- contractions, SNS- relaxation

Absorbtion: vit., proteins, carbohydrates, Absorbtion: vit., proteins, carbohydrates, water, electrolytes are all absorbed water, electrolytes are all absorbed

INVESTIGATIONSINVESTIGATIONSSMALL BOWEL DISORDERSSMALL BOWEL DISORDERS

Radiology- plain erect film- obstruction and Radiology- plain erect film- obstruction and perforationperforationSmall bowel follow-through- the established Small bowel follow-through- the established investigation to outline the small bowel- investigation to outline the small boweltumors, Crohn’s disease, fistulas, polyps.tumors, Crohn’s disease, fistulas, polyps.EnteroclysisEnteroclysisRadiological criteria for malabsorbtion: Radiological criteria for malabsorbtion: flocculation of barium, thickening of the flocculation of barium, thickening of the mucosal folds, loop dilatation mucosal folds, loop dilatation

SBFTSBFT(small bowel follow through)(small bowel follow through)

The esophagus, stomach, and duodenum are easily The esophagus, stomach, and duodenum are easily evaluated in detail. evaluated in detail.

The small bowel is then radiographed at periodic The small bowel is then radiographed at periodic intervals and fluoroscopically spotted by the attending intervals and fluoroscopically spotted by the attending Radiologist. Radiologist.

This type of SBFT can take hours to complete and detail This type of SBFT can take hours to complete and detail of the lumen cannot be assessed as the loops of small of the lumen cannot be assessed as the loops of small intestine overlap as the barium progresses. intestine overlap as the barium progresses.

A better diagnostic tool would be an enteroclysis small A better diagnostic tool would be an enteroclysis small bowel exam. "Entero" is Greek for intestine. bowel exam. "Entero" is Greek for intestine.

"Clysis" is Greek for washing out. "Clysis" is Greek for washing out. Thus, enteroclysis is washing out of the intestine.Thus, enteroclysis is washing out of the intestine.

EnteroclysisEnteroclysis

It is a minimally invasive radiographic procedure of the It is a minimally invasive radiographic procedure of the small intestine, which requires the introduction of a small intestine, which requires the introduction of a catheter into the small intestine followed by the injection catheter into the small intestine followed by the injection of barium and methylcellulose. of barium and methylcellulose.

The barium coats the intestine and the methylcellulose The barium coats the intestine and the methylcellulose distends the lumen to give a double contrast exam that distends the lumen to give a double contrast exam that allows for fluoroscopic visualization of the entire small allows for fluoroscopic visualization of the entire small bowel. bowel.

The enteroclysis study may be helpful in diagnosing almost The enteroclysis study may be helpful in diagnosing almost all diseases that affect the small bowel.all diseases that affect the small bowel.

It may also be helpful in ruling out diseases in patients with It may also be helpful in ruling out diseases in patients with unexplained abdominal complaints.unexplained abdominal complaints.

Indications:Indications:

Suspected or known small bowel obstruction Suspected or known small bowel obstruction

Neoplasms (cancers) Neoplasms (cancers)

Inflammatory bowel disease Inflammatory bowel disease

Unexplained gastrointestinal bleeding Unexplained gastrointestinal bleeding

Malabsorption Malabsorption

Polyps Polyps

Adhesive bands Adhesive bands

Post surgical changes Post surgical changes

DisadvantagesDisadvantages

There are two drawbacks:There are two drawbacks:

The placement of the enteroclysis catheter is the largest The placement of the enteroclysis catheter is the largest disadvantage. It can be uncomfortable for the patient, even disadvantage. It can be uncomfortable for the patient, even with the use of anesthetic spray and Xylocaine jelly or a with the use of anesthetic spray and Xylocaine jelly or a similar lidocaine product. similar lidocaine product.

The patient will receive higher doses of radiation in The patient will receive higher doses of radiation in comparison to the traditional small bowel follow through comparison to the traditional small bowel follow through exam during this exam. exam during this exam.

AdvantagesAdvantages

This examination is much quicker than a routine single This examination is much quicker than a routine single contrast Small Bowel Follow Through exam. contrast Small Bowel Follow Through exam.

There is an increase in the distention of the lumen, which There is an increase in the distention of the lumen, which is very important; the distention straightens the circular is very important; the distention straightens the circular folds and will help to determine: fold thickness, folds and will help to determine: fold thickness, ulceration, polyps, constrictions, and adhesive bands are ulceration, polyps, constrictions, and adhesive bands are more readily identified. more readily identified.

Distention of the small bowel makes it possible to display Distention of the small bowel makes it possible to display all dilated bowel loops simultaneously at the end of the all dilated bowel loops simultaneously at the end of the exam. exam.

The catheter is being held up at the pylorus. The catheter is being held up at the pylorus. When this occurs, rolling the patient to the left will When this occurs, rolling the patient to the left will widen the bulb, allowing the catheter to advance widen the bulb, allowing the catheter to advance

into the duodenum.into the duodenum.

JejunumJejunum

MethylcelluloseMethylcelluloseMethylcellulose has a natural tendency to retain water in the lumen, Methylcellulose has a natural tendency to retain water in the lumen,

which promotes peristalsis and prevents lumen collapse. When used in which promotes peristalsis and prevents lumen collapse. When used in an Enteroclysis study, this product mixes with the barium and produces an Enteroclysis study, this product mixes with the barium and produces

the desired air contrast effect.the desired air contrast effect.

Enteroclysis parametersEnteroclysis parameters

Fold shapeFold shape Fold thicknessFold thickness


Fold heightFold height Number of folders/inchNumber of folders/inch


Wall thicknessWall thickness Lumen diameterLumen diameter

INVESTIGATIONSINVESTIGATIONSSMALL BOWELSMALL BOWEL

Selective splanhnic angiography- reliable Selective splanhnic angiography- reliable method for detection of angioplastic method for detection of angioplastic lesionslesions

The bleeding site can be located if the The bleeding site can be located if the patient is bleeding actively at the time of patient is bleeding actively at the time of investigationinvestigation


USS of the abdomenUSS of the abdomen

Can differentiate fluid-filled dilated small Can differentiate fluid-filled dilated small bowel loop from abdominal cystic bowel loop from abdominal cystic structuresstructures

Can assess free fluid within peritoneal Can assess free fluid within peritoneal cavitycavity

Can assess a solid mass belonging to the Can assess a solid mass belonging to the small bowel if large enoughsmall bowel if large enough


Isotope scintigraphyIsotope scintigraphyIsotope-labelled red cells- occult GI Isotope-labelled red cells- occult GI bleedingbleedingIsotope-labelled white cells- suspected Isotope-labelled white cells- suspected intraabdominal inflammation/abscess intraabdominal inflammation/abscess formation, inflammed bowel (Crohn’s formation, inflammed bowel (Crohn’s disease)disease)Isotope labelled meal- intestinal transit Isotope labelled meal- intestinal transit timetime


Estimation of fecal fat- the quantitative Estimation of fecal fat- the quantitative estimation of fecal fat remains the most estimation of fecal fat remains the most sensitive test of disorders of digestion and sensitive test of disorders of digestion and absorbtionabsorbtion

On a standard diet of 100g. of fat, the fecal On a standard diet of 100g. of fat, the fecal fat output normally is less than 6g./dayfat output normally is less than 6g./day


Jejunal mucosal biopsyJejunal mucosal biopsy

Celiac disease- subtotal villous atrophyCeliac disease- subtotal villous atrophy

Whipple’s- abnormal mucosal pathogensWhipple’s- abnormal mucosal pathogens


Breath Tests- detection of bacterial Breath Tests- detection of bacterial overgrowth, carbohydrate malabsorbtion overgrowth, carbohydrate malabsorbtion and small bowel transitand small bowel transit

Hydrogen Breath Test- small bowel transit Hydrogen Breath Test- small bowel transit time and bacterial overgrowthtime and bacterial overgrowth

Consists of repeated measurements of the Consists of repeated measurements of the H2 in the end-expiratory air taken every H2 in the end-expiratory air taken every few minutes after ingestion of a meal few minutes after ingestion of a meal

HYDROGEN BREATH TESTHYDROGEN BREATH TEST

When the radiolabelled meal reaches the When the radiolabelled meal reaches the cecum, the resulting bacterial fermentation cecum, the resulting bacterial fermentation induces a sustained rise in the breath H2 induces a sustained rise in the breath H2 concentrationconcentrationThe test measures the oral- cecal transit The test measures the oral- cecal transit time which includes gastric emptying timetime which includes gastric emptying timeIn pts. with bacterial overgrowth, the In pts. with bacterial overgrowth, the fasting H2 level in the expired breath is fasting H2 level in the expired breath is elevatedelevated

BACTERIAL OVERGROWTHBACTERIAL OVERGROWTH

The small bowel becomes colonized by The small bowel becomes colonized by bacteriabacteriaThere is an increase in the concentration There is an increase in the concentration organisms which are normally confined to organisms which are normally confined to the lower small bowel and colonthe lower small bowel and colonThe affected intestine becomes inflammed The affected intestine becomes inflammed and dilatedand dilatedSymptoms and signs- colicky pain, Symptoms and signs- colicky pain, meteorism, diarrhea, anemiameteorism, diarrhea, anemia


Causes of bacterial overgrowth:Causes of bacterial overgrowth:

1. Excessive entry of bacteria into the 1. Excessive entry of bacteria into the small bowelsmall bowel

2. Intestinal stasis2. Intestinal stasis


1. Excessive entry of bacteria1. Excessive entry of bacteria– AchlorhydriaAchlorhydria– Gastro-jejunostomyGastro-jejunostomy– GastrectomyGastrectomy– Enterocolic fistulasEnterocolic fistulas– CholangitisCholangitis– Loss of ileocecal valve following RHCLoss of ileocecal valve following RHC


2. Intestinal stasis:2. Intestinal stasis:– Stenotic Crohn’s diseaseStenotic Crohn’s disease– Stenotic intestinal stasisStenotic intestinal stasis– Small bowel diverticulosisSmall bowel diverticulosis– Afferent loop stasisAfferent loop stasis– Entero- enteric anastomosisEntero- enteric anastomosis– Diabetis mellitus- autonomic neuropathyDiabetis mellitus- autonomic neuropathy– Radiation enteritis- stenosisRadiation enteritis- stenosis– Scleroderma- impaired intestinal motilityScleroderma- impaired intestinal motility


Clinical features:Clinical features:– Abdominal colicky painAbdominal colicky pain– Asthenia, nausea, vomitingAsthenia, nausea, vomiting– Weight loss, excessive bowel soundsWeight loss, excessive bowel sounds– DiarrheaDiarrhea– Anemia, hypoproteinemiaAnemia, hypoproteinemia– Paresthesia, peripheral neuropathy- B12 Paresthesia, peripheral neuropathy- B12

deficiency deficiency


TreatmentTreatment– Surgical treatment of the underlying condition Surgical treatment of the underlying condition

whenever possiblewhenever possible

– Jejunal diverticulosis, scleroderma- Jejunal diverticulosis, scleroderma- tetracycline and metronidazol for 10-14 daystetracycline and metronidazol for 10-14 days

SHORT-GUT SYNDROMESHORT-GUT SYNDROME

Encountered after massive resection of Encountered after massive resection of the small bowelthe small bowel

Encountered in pts. with jejuno-ileal by-Encountered in pts. with jejuno-ileal by-pass for morbid obesitypass for morbid obesity


Conditions necessitating extensive Conditions necessitating extensive resection of the small bowel:resection of the small bowel:– Crohn’s diseaseCrohn’s disease– Mesenteric infarctionMesenteric infarction– Radiation enteritisRadiation enteritis– Multiple fistulasMultiple fistulas– Small bowel tumorsSmall bowel tumors

SHORT GUT SYNDROMESHORT GUT SYNDROME

Resections of more than half of the small Resections of more than half of the small bowel length- serious malabsorbtionbowel length- serious malabsorbtionPts.with residual small bowel length of less Pts.with residual small bowel length of less 2m.- diminished work capacity2m.- diminished work capacityPts. with residual small bowel length of Pts. with residual small bowel length of less 1m. require home parenteral nutrition less 1m. require home parenteral nutrition on an indefinite basison an indefinite basisIleal resections are less well tolerated than Ileal resections are less well tolerated than jejunal resectionsjejunal resections


Clinical outcome following small bowel Clinical outcome following small bowel resection depending on:resection depending on:

– Extent and site of resectionExtent and site of resection– Age of the patientAge of the patient– Physical and mental conditionPhysical and mental condition


Treatment:Treatment:– Massive small bowel resection- TPNMassive small bowel resection- TPN– The regimen must provide 40 Kcal/Kg. body The regimen must provide 40 Kcal/Kg. body

weightweight– Pts. with about 1m. of small bowel, TPN Pts. with about 1m. of small bowel, TPN

discontinued with time- small bowel will discontinued with time- small bowel will hypertrophy hypertrophy

– Oral nutrition is based on an elemental dietOral nutrition is based on an elemental diet– antiperistaltic agents should be given, antiperistaltic agents should be given,

vitamins, B12 parenteralvitamins, B12 parenteral

PROTEIN-LOSING PROTEIN-LOSING ENTEROPATHYENTEROPATHY

Loss of plasma proteins- low plasma Loss of plasma proteins- low plasma proteins- secondary hyperaldosteronism proteins- secondary hyperaldosteronism with water and salt retention- edemawith water and salt retention- edema

Causes:- mucasal disease- Whipple’s,Causes:- mucasal disease- Whipple’s,

- ulcerating lesions- villous tumors- ulcerating lesions- villous tumors

- lymphatic obstruction- - lymphatic obstruction- lymphomalymphoma

Treat the underlying diseaseTreat the underlying disease

SMALL BOWEL TUMORSSMALL BOWEL TUMORS

10% of all GI tumors (benign or malignant)10% of all GI tumors (benign or malignant)

Benign small bowel tumors:Benign small bowel tumors:– Adenomatous polypsAdenomatous polyps– Hamartomatous polyps- Peutz-Jagers sdr.Hamartomatous polyps- Peutz-Jagers sdr.– Leiomyomas, lipomas, fibromasLeiomyomas, lipomas, fibromas– Hemangiomas, neurofibromas Hemangiomas, neurofibromas

BENIGN SMALL BOWEL BENIGN SMALL BOWEL TUMORSTUMORS

Clinical presentations:Clinical presentations:– Bowel obstruction due to intussusceptionBowel obstruction due to intussusception– Chronic blood loss- chronic anemia- fecal ocult blood Chronic blood loss- chronic anemia- fecal ocult blood

test+test+– Melena- acute anemiaMelena- acute anemiaDIAGNOSIS- barium follow-throughDIAGNOSIS- barium follow-through

- abdominal CT- abdominal CT - endoscopic videocapsule for - endoscopic videocapsule for nonobstructing lesions nonobstructing lesions

TREATMENT- bowel resection with end to end TREATMENT- bowel resection with end to end anastomosis anastomosis

MALIGNANT SMALL BOWEL MALIGNANT SMALL BOWEL TUMORSTUMORS

ADENOCARCINOMASADENOCARCINOMAS

MALIGNANT CARCINOIDMALIGNANT CARCINOID

LYMPHOMALYMPHOMA

METASTASES FROM DISTANT TU.METASTASES FROM DISTANT TU.

MALIGNANT SMALL BOWEL MALIGNANT SMALL BOWEL TUMORSTUMORS

Clinical presentations:Clinical presentations:– Lower GI bleeding- ocult or melenaLower GI bleeding- ocult or melena– DiarrheaDiarrhea– Perforation- peritonitisPerforation- peritonitis– Bowel obstructionBowel obstruction

DIAGNOSIS- contrast follow-through, CT for DIAGNOSIS- contrast follow-through, CT for elective cases, plain abdo X ray- acute caseselective cases, plain abdo X ray- acute cases

TREATMENT- segmental bowel resection TREATMENT- segmental bowel resection

SMALL BOWEL SMALL BOWEL ADENOCARCINOMAADENOCARCINOMA

Commonly- well-differentiated mucus-Commonly- well-differentiated mucus-secreting tumorssecreting tumors

Usually located in the proximal intestineUsually located in the proximal intestine

Spreading to lymph nodes, liver, peritoneal Spreading to lymph nodes, liver, peritoneal serosaserosa

Pts. with resectable tumors, 25%- 5 year-Pts. with resectable tumors, 25%- 5 year-survival rate survival rate

CARCINOID TUMORSCARCINOID TUMORS

Derived from enterochromaffin cellsDerived from enterochromaffin cells

ApudomasApudomas

Common places: appendix, ileum, rectumCommon places: appendix, ileum, rectum

Clinical features: flushing, diarrhea, Clinical features: flushing, diarrhea, bronchoconstriction caused by serotonin bronchoconstriction caused by serotonin and other vasoactive substances secreted and other vasoactive substances secreted by the tumorby the tumor

CARCINOID TUMORCARCINOID TUMOR

Diagnosis- elevated levels of 5 HIAA-Diagnosis- elevated levels of 5 HIAA-

5 hydroxyindolacetic acid- the breakdown 5 hydroxyindolacetic acid- the breakdown product of serotonin in the urineproduct of serotonin in the urine

TREATMENT- resection of the primary TREATMENT- resection of the primary tumor and resection of the metastasestumor and resection of the metastases

GIST- GI STROMAL TUMORSGIST- GI STROMAL TUMORS

• Most common gastrointestinal (GI) sarcoma– A tumor of mesenchymal (connective tissue) origin– 0.2% of all GI tumors, but 80% of GI sarcomas

• Highest incidence in the 40-60 year age group– Similar male/female incidence, although some reports suggest a

slightly higher incidence in men• Recently identified as a distinct clinical and histopathologic entity

– Previously misclassified as leiomyosarcoma/other spindle cell cancers• GIST have an incidence of 14.5 per million annually (comparable

with chronic myeloid leukemia) and a prevalence of 129 per million

GIST-CLINICAL PRESENTATIONGIST-CLINICAL PRESENTATION

• Often asymptomatic, especially when small– May be symptomatic if large

• Symptomatic: signs/symptoms related to location and size of tumor– Vague GI pain or discomfort

– GI hemorrhage

– Anemia

– Anorexia, weight loss, nausea, fatigue, and additional GI complaints

– Acute intraperitoneal bleeding or perforation

GIST- SITES OF GROWTHGIST- SITES OF GROWTH

50%Stomach

25%Small

intestine

10% 15%

Colon Other (rectum, esophagus, mesentery, retroperitoneum)

50%Stomach

25%Small

intestine

10% 15%

Colon Other (rectum, esophagus, mesentery, retroperitoneum)

GISTGIST

• GIST have 2 major histologic patterns, which overlap with many non-GIST sarcomas and other malignancies

– Spindle cell

– Epithelioid

• In the past, GIST were usually classified as

– Leiomyoma

– Leiomyoblastoma

– Leiomyosarcoma

• Many patients previously diagnosed with one of these tumors actually had a GIST

GIST-IMMUNOPHENOTYPEGIST-IMMUNOPHENOTYPE

• ~95% of reported cases of GIST are positive for KIT (CD117)

• Other markers often positive in GIST– CD34 (mesenchymal/hematopoietic

precursor cell marker)• Positive in 60%-70%

– Smooth-muscle actin• Positive in 15%-60%

– S-100• Positive in 10%

• GIST rarely express desmin

GIST-ASSESSMENT MALIGNANT GIST-ASSESSMENT MALIGNANT POTENTIALPOTENTIAL

Risk Size Mitotic Rate

High Any size >10/50 HPF

>10 cm Any rate

>5 cm >5/50 HPF

Intermediate 5-10 cm <5/50 HPF

<5 cm 6-10/50 HPF

Low 2-5 cm <5/50 HPF

Very low <2 cm <5/50 HPF

GIST OVERVIEWGIST OVERVIEW

• GIST is the most common sarcoma of the GI tract – May arise from the same stem cells as ICC of the myenteric

plexus

• Pathologic characteristics of GIST are now well defined, but diagnosis remains challenging in some cases

• Clinical presentation is variable– Tumors are often asymptomatic

– Patients may have common, nonspecific symptoms, resulting in underdiagnosis or misdiagnosis

• All GIST have the potential to become malignant– Risk is based on size and mitotic index at presentation

NORMAL BIOLOGIC FUNCTION OF NORMAL BIOLOGIC FUNCTION OF KIT RECEPTOR TYROZINE KINASEKIT RECEPTOR TYROZINE KINASE

• KIT is essential for– Hematopoiesis – Skin pigment– Fertility– Gut motility (pacemaker cells)

• KIT plays a role in different cell functions– Proliferation – Differentiation – Apoptosis/survival – Adhesion/chemotaxis

• Familial gain-of-function KIT mutations result in high incidence of GIST, melanocytic dysfunction, and cutaneous mastocytosis

GIST DIAGNOSISGIST DIAGNOSIS

• Initial GIST patient workup should include imaging– CT of abdomen and pelvis with oral/IV contrast

– Consider 18FDG-PET

– Endoscopic ultrasound

• Liver function tests

• Complete blood counts

• Surgical assessment – Resectable vs nonresectable

– Primary tumor only vs metastatic

GIST METHODS OF DETECTIONGIST METHODS OF DETECTION

• Endoscopic ultrasound (EUS)

• MRI

• CT

• 18FDG-PET

ENDOSCOPY AND EUSENDOSCOPY AND EUS

ULCERATED GASTRIC GISTULCERATED GASTRIC GIST

EUS- Homogenous submucosal EUS- Homogenous submucosal massmass

CT- Massive stromal gastric tumorCT- Massive stromal gastric tumorEndobiopsy negativeEndobiopsy negative

Positron Emission TomographyPositron Emission Tomography

• Diagnosis– 18FDG-PET is highly sensitive, but not

specific, for metabolically active GIST

• Staging workup– Evaluate the extent of the disease

– Assess for metastatic disease

FDG - PETFDG - PET

Fluorodeoxyglucose- positron emission Fluorodeoxyglucose- positron emission tomography:tomography:

– Provides the status of glucose metabolism in Provides the status of glucose metabolism in tumorstumors

– GIST are highly metabolically activeGIST are highly metabolically active– Easily detected with FDG-PETEasily detected with FDG-PET

GIST FDG-PET ImagingGIST FDG-PET ImagingHepatic, abdominal and pelvic Hepatic, abdominal and pelvic

metastasesmetastases

CT AND FGD-PETCT AND FGD-PET

• Patients with suspected GIST should be evaluated using CT and possibly 18FDG-PET

• CT provides anatomic detail of tumor(s) for possible surgical resection and may suggest diagnosis

• 18FDG-PET may detect small tumors and can be used as an indicator of early response to treatment

GIST- TREATMENTGIST- TREATMENT

• Standard sarcoma chemotherapy is ineffective– Limited response rate ~5%

– Median time to progression 3-4 months

– No impact on survival

• Comorbidity due to tumor localization limits effectiveness of radiation therapy– Possible role in treatment of rectal tumors

• Surgery remains the principal treatment for resectable primary GIST

GIST- SURGERY FOR PRIMARY GIST- SURGERY FOR PRIMARY TUMORSTUMORS

• Complete gross resection of tumor with pseudocapsule

• Fragility of tumor risks rupture– Bleeding

– Dissemination

• Abdomen should be examined for metastases– Peritoneal surfaces

– Liver

• GIST can often be lifted off surrounding organs

SURGICAL SURGICAL CONSIDERATIONSCONSIDERATIONS

• Complete gross resection with the intact pseudocapsule is the goal of resection– Careful tumor handling is critical

– Rupturing of the pseudocapsule can cause tumor bleeding and/or dissemination

• Unlike adenocarcinomas, GIST tend to displace, not invade, surrounding organs

• Negative microscopic margins are desirable

• Lymphadenectomy is unnecessary, as GIST rarely metastasize to the regional lymph nodes

RECURRENCE AFTER SURGERYRECURRENCE AFTER SURGERY

• After surgery, recurrence is common– Majority of high-risk patients have recurrence of GIST

following surgery

– Median time to recurrence is 7 months to 2 years

– Only 10% of patients remain disease-free after extended follow-up

– Investigational protocols are indicated to reduce the rate of recurrence after resection

– Recurrent disease should be treated as metastatic disease

NEOADJUVANT IMATINIB NEOADJUVANT IMATINIB MESYLATE THERAPY FOR GISTMESYLATE THERAPY FOR GIST

• Few complete responses with imatinib mesylate therapy – Most responding lesions have viable cells

• Cytoreduction may improve surgical outcomes

• Potential to increase resectability or reduce the extent of surgery

GIST TREATMENT OPTIONSGIST TREATMENT OPTIONS

• Intermediate and high-risk GIST have a high rate of recurrence

– Recurrent disease should be treated as metastatic disease

• Traditional chemotherapy and radiation therapy are ineffective for GIST

• Patient follow-up is necessary

• Neoadjuvant therapy may enhance resectability

• Adjuvant therapy may reduce recurrence

MECHANISM OF ACTIONMECHANISM OF ACTION

• Imatinib mesylate occupies the ATP binding pocket of the KIT kinase domain

• This prevents substrate phosphorylation and signaling

• A lack of signaling inhibits proliferation and survival

TYROSINE KINASE INHIBITORSTYROSINE KINASE INHIBITORSMOLECULARLY TARGETED MOLECULARLY TARGETED

THERAPYTHERAPY• ~90% of GIST have an oncogenic mutation of KIT or

PDGFRA • Mutations occur early in GIST development

– KIT mutations are detectable in incidental tumors 1cm– Patients with germline KIT mutations develop multiple GIST– KIT mutations precede cytogenetic changes in GIST development

• Imatinib mesylate is a specific inhibitor of KIT tyrosine kinase activity and blocks KIT-mediated downstream signaling

SCIENTIFIC RATIONALE FOR SCIENTIFIC RATIONALE FOR IMATINIB MESYLATE IN THE IMATINIB MESYLATE IN THE

TREATMENT OF GISTTREATMENT OF GIST

• Imatinib mesylate is an ATP-mimetic TKI of the KIT, Bcr-Abl, and PDGFRA/B receptors

• In cell culture experiments, imatinib mesylate effectively inhibits activated KIT, resulting in death of GIST cells in culture

JEJUNAL STROMAL TUMOR JEJUNAL STROMAL TUMOR WITH MUCOSAL ULCERATIONWITH MUCOSAL ULCERATION

INTRAOPERATIVE VIEW- INTRAOPERATIVE VIEW- JEJUNAL STROMAL TUMORJEJUNAL STROMAL TUMOR

RESECTED SPECIMENRESECTED SPECIMENTUMOR WITH A SEGMENT OF JEJUNUMTUMOR WITH A SEGMENT OF JEJUNUM

RESECTED SPECIMENRESECTED SPECIMEN

MACROSCOPIC TUMORAL MACROSCOPIC TUMORAL ASPECTASPECT

ENDOSCOPIC VIEW TAKEN BY ENDOSCOPIC VIEW TAKEN BY SWOLLEN VIDEOCAPSULESWOLLEN VIDEOCAPSULE

PROTRUSIVE ENDOLUMINAL TUMOR OF THE PROTRUSIVE ENDOLUMINAL TUMOR OF THE JEJUNAL WALLJEJUNAL WALL

SMALL MUCOSAL LACERATION RESPONSIBLE SMALL MUCOSAL LACERATION RESPONSIBLE FOR HDIFOR HDI

DOUBLE CONTRASTDOUBLE CONTRAST FOLLOW-THROUGH FOLLOW-THROUGH

DOUBLE CONTRASTDOUBLE CONTRASTFOLLOW- THROUGHFOLLOW- THROUGH

USS of the UPPER ABDOMENUSS of the UPPER ABDOMEN

SMALL BOWEL DIVERTICULOSISSMALL BOWEL DIVERTICULOSIS

Duodenal diverticula- 90% are asymptomaticDuodenal diverticula- 90% are asymptomatic70% -periampullary region- cholangitis, 70% -periampullary region- cholangitis, pancreatitis, CBD stonespancreatitis, CBD stonesJejunal diverticula-rare, may cause obstruction, Jejunal diverticula-rare, may cause obstruction, bleeding, perforation, bacterial overgrowth within bleeding, perforation, bacterial overgrowth within the diverticulumthe diverticulumMeckel’s diverticulum- within 40 cm. of the Meckel’s diverticulum- within 40 cm. of the ileocecal valveileocecal valveMeckel’s diverticulum may cause bleeding, Meckel’s diverticulum may cause bleeding, obstruction, acute inflammationobstruction, acute inflammation

TREATMENT- resection with enteroraphyTREATMENT- resection with enteroraphy

ACUTE APPENCITISACUTE APPENCITIS

Commonest condition requiring acute Commonest condition requiring acute abdominal surgeryabdominal surgeryThe peak incidence in the 2The peak incidence in the 2ndnd-3-3rdrd decades decadesEtiology:Etiology:– Obstruction of the lumen (fecaliths, worms, Obstruction of the lumen (fecaliths, worms,

cecal cancer)cecal cancer)– Persistent appendiceal secretions, distention Persistent appendiceal secretions, distention

with inflammation, bacterial overgrowth, with inflammation, bacterial overgrowth, ischemia, gangrene, perforationischemia, gangrene, perforation

ACUTE APPENDICITISACUTE APPENDICITISDIAGNOSISDIAGNOSIS

History 1-12 h. of digestive symptomsHistory 1-12 h. of digestive symptoms

Symptoms: RIF pain, anorexia, nausea, Symptoms: RIF pain, anorexia, nausea, vomitingvomiting

Physical signs: fever, tachycardia, RIF Physical signs: fever, tachycardia, RIF guarding, rebound tenderness, Rowsig’s guarding, rebound tenderness, Rowsig’s sign, psoas signsign, psoas sign

Lab.tests: WBC elevated, predominance Lab.tests: WBC elevated, predominance of neutrophilsof neutrophils

ACUTE APPENDICITISACUTE APPENDICITISCOMPLICATIONS IF LEFT UNTREATEDCOMPLICATIONS IF LEFT UNTREATED

Perforation with localized peritonitisPerforation with localized peritonitis

Appendiceal inflammatory massAppendiceal inflammatory mass

Appendiceal abscess +/- diffuse peritonitisAppendiceal abscess +/- diffuse peritonitis

SepticemiaSepticemia

Multiple Systemic Organ FailureMultiple Systemic Organ Failure

ACUTE APPENDICITISACUTE APPENDICITISDIFFERENTIAL DIAGNOSISDIFFERENTIAL DIAGNOSIS

Mesenteric lymphadenitisMesenteric lymphadenitis

Chrohn’s disease- flare upChrohn’s disease- flare up

Pelvic inflammatory diseasePelvic inflammatory disease

Ruptures ovarian cystRuptures ovarian cyst

Ureteric calculi, UTIUreteric calculi, UTI

Sigmoid diverticulitisSigmoid diverticulitis

ACUTE APPENDICITISACUTE APPENDICITISTREATMENTTREATMENT

Broad-spectrum antibioticsBroad-spectrum antibiotics

Iv. fluids, nil by mouth more than 6 h. Iv. fluids, nil by mouth more than 6 h. preoperatively.preoperatively.

Laparoscopic / open appendicectomyLaparoscopic / open appendicectomyDrainage depending on the severity of the Drainage depending on the severity of the

lesionlesion

powerpoint: lecture 10, the small bowel and appendix

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