Powerpoint: Lecture 10, The Small Bowel And Appendix

THE SMALL BOWEL AND APPENDIX

ANATOMY SMALL BOWEL Three regions: duodenum, jejunum and ileum Duodenum- deeply placed ,C-shaped, receives bile and pancreatic juice through Vater ampulla- D2 Jejunum- upper left part of the abdo. cavity Ileum- lower right part of the abdominal and pelvic cavity

6 m small bowel 2/5 jejunum, 3/5 ileum

ANATOMY SMALL BOWEL Jejunum is larger in diameter, thicker walled, more prominent mucosal folds Arterial supply – branches of the SMA Absorbtion area of the nutrients- 500 m2 Submucosa is the strongest layer, provides strength to an intestinal anastomosis

PHYSIOLOGY SMALL BOWEL The primary functions: digestion and absorbtion All ingested food and fluid and secretions from the stomach, liver, pancreas reach the small bowel- total volume- 9 l /day and all but 1-2l will be absorbed

PHYSIOLOGY SMALL BOWEL Motility- two types of contractions To-and-fro motion mixes chyme with digestive juices for prolonged exposure to the absorbative mucosa Peristaltic contractions move food distally PNS- contractions, SNS- relaxation Absorbtion: vit., proteins, carbohydrates, water, electrolytes are all absorbed

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

SBFT (small bowel follow through) The esophagus, stomach, and duodenum are easily evaluated in detail. The small bowel is then radiographed at periodic intervals and fluoroscopically spotted by the attending Radiologist. This type of SBFT can take hours to complete and detail of the lumen cannot be assessed as the loops of small intestine overlap as the barium progresses.

A better diagnostic tool would be an enteroclysis small bowel exam. "Entero" is Greek for intestine. "Clysis" is Greek for washing out. Thus, enteroclysis is washing out of the intestine.

Enteroclysis It is a minimally invasive radiographic procedure of the small intestine, which requires the introduction of a catheter into the small intestine followed by the injection of barium and methylcellulose. The barium coats the intestine and the methylcellulose distends the lumen to give a double contrast exam that allows for fluoroscopic visualization of the entire small bowel.

The enteroclysis study may be helpful in diagnosing almost all diseases that affect the small bowel. It may also be helpful in ruling out diseases in patients with unexplained abdominal complaints. Indications: Suspected or known small bowel obstruction Neoplasms (cancers) Inflammatory bowel disease Unexplained gastrointestinal bleeding Malabsorption Polyps Adhesive bands Post surgical changes

Disadvantages There are two drawbacks: The placement of the enteroclysis catheter is the largest disadvantage. It can be uncomfortable for the patient, even with the use of anesthetic spray and Xylocaine jelly or a similar lidocaine product. The patient will receive higher doses of radiation in comparison to the traditional small bowel follow through exam during this exam.

Advantages This examination is much quicker than a routine single contrast Small Bowel Follow Through exam. There is an increase in the distention of the lumen, which is very important; the distention straightens the circular folds and will help to determine: fold thickness, ulceration, polyps, constrictions, and adhesive bands are more readily identified. Distention of the small bowel makes it possible to display all dilated bowel loops simultaneously at the end of the exam.

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

Jejunum

Methylcellulose Methylcellulose has a natural tendency to retain water in the lumen, which promotes peristalsis and prevents lumen collapse. When used in an Enteroclysis study, this product mixes with the barium and produces the desired air contrast effect.

Enteroclysis parameters Fold shape

Fold thickness

Enteroclysis parameters Fold height

Number of folders/inch

Enteroclysis parameters Wall thickness

Lumen diameter

INVESTIGATIONS SMALL BOWEL Selective splanhnic angiography- reliable method for detection of angioplastic lesions The bleeding site can be located if the patient is bleeding actively at the time of investigation

INVESTIGATIONS SMALL BOWEL USS of the abdomen Can differentiate fluid-filled dilated small bowel loop from abdominal cystic structures Can assess free fluid within peritoneal cavity Can assess a solid mass belonging to the small bowel if large enough

INVESTIGATIONS SMALL BOWEL Isotope scintigraphy Isotope-labelled red cells- occult GI bleeding Isotope-labelled white cells- suspected intraabdominal inflammation/abscess formation, inflammed bowel (Crohn’s disease) Isotope labelled meal- intestinal transit time

INVESTIGATIONS SMALL BOWEL Estimation of fecal fat- the quantitative estimation of fecal fat remains the most sensitive test of disorders of digestion and absorbtion On a standard diet of 100g. of fat, the fecal fat output normally is less than 6g./day

INVESTIGATIONS SMALL BOWEL Jejunal mucosal biopsy Celiac disease- subtotal villous atrophy Whipple’s- abnormal mucosal pathogens

INVESTIGATIONS SMALL BOWEL Breath Tests- detection of bacterial overgrowth, carbohydrate malabsorbtion and small bowel transit Hydrogen Breath Test- small bowel transit time and bacterial overgrowth Consists of repeated measurements of the H2 in the end-expiratory air taken every few minutes after ingestion of a meal

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

BACTERIAL OVERGROWTH The small bowel becomes colonized by bacteria There is an increase in the concentration organisms which are normally confined to the lower small bowel and colon The affected intestine becomes inflammed and dilated Symptoms and signs- colicky pain, meteorism, diarrhea, anemia

BACTERIAL OVERGROWTH Causes of bacterial overgrowth: 1. Excessive entry of bacteria into the small bowel 2. Intestinal stasis

BACTERIAL OVERGROWTH 1. Excessive entry of bacteria – Achlorhydria – Gastro-jejunostomy – Gastrectomy – Enterocolic fistulas – Cholangitis – Loss of ileocecal valve following RHC

BACTERIAL OVERGROWTH 2. Intestinal stasis: – Stenotic Crohn’s disease – Stenotic intestinal stasis – Small bowel diverticulosis – Afferent loop stasis – Entero- enteric anastomosis – Diabetis mellitus- autonomic neuropathy – Radiation enteritis- stenosis – Scleroderma- impaired intestinal motility

BACTERIAL OVERGROWTH Clinical features: – – – – – –

Abdominal colicky pain Asthenia, nausea, vomiting Weight loss, excessive bowel sounds Diarrhea Anemia, hypoproteinemia Paresthesia, peripheral neuropathy- B12 deficiency

BACTERIAL OVERGROWTH Treatment – Surgical treatment of the underlying condition whenever possible – Jejunal diverticulosis, sclerodermatetracycline and metronidazol for 10-14 days

SHORT-GUT SYNDROME Encountered after massive resection of the small bowel

Encountered in pts. with jejuno-ileal bypass for morbid obesity

SHORT-GUT SYNDROME Conditions necessitating extensive resection of the small bowel: – Crohn’s disease – Mesenteric infarction – Radiation enteritis – Multiple fistulas – Small bowel tumors

SHORT GUT SYNDROME Resections of more than half of the small bowel length- serious malabsorbtion Pts.with residual small bowel length of less 2m.- diminished work capacity Pts. with residual small bowel length of less 1m. require home parenteral nutrition on an indefinite basis Ileal resections are less well tolerated than jejunal resections

SHORT-GUT SYNDROME Clinical outcome following small bowel resection depending on: – Extent and site of resection – Age of the patient – Physical and mental condition

SHORT-GUT SYNDROME Treatment: – Massive small bowel resection- TPN – The regimen must provide 40 Kcal/Kg. body weight – Pts. with about 1m. of small bowel, TPN discontinued with time- small bowel will hypertrophy – Oral nutrition is based on an elemental diet – antiperistaltic agents should be given, vitamins, B12 parenteral

PROTEIN-LOSING ENTEROPATHY Loss of plasma proteins- low plasma proteins- secondary hyperaldosteronism with water and salt retention- edema Causes:- mucasal disease- Whipple’s, - ulcerating lesions- villous tumors - lymphatic obstruction- lymphoma Treat the underlying disease

SMALL BOWEL TUMORS 10% of all GI tumors (benign or malignant) Benign small bowel tumors: – Adenomatous polyps – Hamartomatous polyps- Peutz-Jagers sdr. – Leiomyomas, lipomas, fibromas – Hemangiomas, neurofibromas

BENIGN SMALL BOWEL TUMORS Clinical presentations: – Bowel obstruction due to intussusception – Chronic blood loss- chronic anemia- fecal ocult blood test+ – Melena- acute anemia DIAGNOSIS- barium follow-through - abdominal CT - endoscopic videocapsule for nonobstructing lesions TREATMENT- bowel resection with end to end anastomosis

MALIGNANT SMALL BOWEL TUMORS ADENOCARCINOMAS MALIGNANT CARCINOID LYMPHOMA METASTASES FROM DISTANT TU.

MALIGNANT SMALL BOWEL TUMORS Clinical presentations: – Lower GI bleeding- ocult or melena – Diarrhea – Perforation- peritonitis – Bowel obstruction

DIAGNOSIS- contrast follow-through, CT for elective cases, plain abdo X ray- acute cases TREATMENT- segmental bowel resection

SMALL BOWEL ADENOCARCINOMA Commonly- well-differentiated mucussecreting tumors Usually located in the proximal intestine Spreading to lymph nodes, liver, peritoneal serosa Pts. with resectable tumors, 25%- 5 yearsurvival rate

CARCINOID TUMORS Derived from enterochromaffin cells Apudomas Common places: appendix, ileum, rectum Clinical features: flushing, diarrhea, bronchoconstriction caused by serotonin and other vasoactive substances secreted by the tumor

CARCINOID TUMOR

Diagnosis- elevated levels of 5 HIAA5 hydroxyindolacetic acid- the breakdown product of serotonin in the urine TREATMENT- resection of the primary tumor and resection of the metastases

GIST- GI STROMAL TUMORS • M o s t c o m m o n g a s tr o in t e s tin a l ( G I) s a r c o m a – A t u m o r o f m e s e n c h y m a l (c o n n e c t iv e t is s u e ) o r ig in – 0 . 2 % o f a ll G I t u m o rs , b u t 8 0 % o f G I s a rc o m a s

• H ig h e s t in c id e n c e in-6 0th yee 4a 0r a g e g r o u p

– S im ila r m a le / fe m a le in c id e n c e , a lt h o u g h s o m e r e p o r ts s u g g e s t s lig h t ly h ig h e r in c id e n c e in m e n

• R e c e n tl y id e n tifie d a s a d is tin c t c lin ic a l a n dn tith isy to p a t h o lo g ic e

– P r e v io u s ly m is c la s s ifie d a s le io m y o s a rc o m a /no ct he ersr s p in d le c e ll c

• G IS T h a v e a n in c id e n c e o f 1 4 .5 p e r m illio n a n n u a ll y ( c o m p a w ith c h r o n ic m y e lo id le u k e m ia ) a n d a p r e v a leonnc e o f 1 2 9 p e r

GIST-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 GROWTH Colon

10%

Other (rectum, esophagus, mesentery, retroperitoneum)

15%

50% Stomach

25% Small intestine

GIST • 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-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 POTENTIAL Risk High

Size Any size >10 cm

Mitotic Rate >10/50 HPF Any rate

>5 cm

>5/50 HPF

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

Intermediate

GIST 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 KIT RECEPTOR TYROZINE KINASE • KIT is ess ential for – – – –

H em atopoiesis S k in pigm ent F ertility G ut m otility (pac em ak er c ells)

– – – –

Proliferation D ifferentiation A poptosis/s urvival A dhes ion/c hem otaxis

• KIT plays a role in different cell functions

• F am ilial gain -of-function KIT m utations result in high incidence of G IST, m elan oc ytic dysfunction, and cutaneous m astoc ytos is

GIST 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 DETECTION • Endoscopic ultrasound (EUS) • MRI • CT • 18FDG-PET

ENDOSCOPY AND EUS

ULCERATED GASTRIC GIST

EUS- Homogenous submucosal mass

CT- Massive stromal gastric tumor Endobiopsy negative

Positron 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 - PET Fluorodeoxyglucose- positron emission tomography: – Provides the status of glucose metabolism in tumors – GIST are highly metabolically active – Easily detected with FDG-PET

GIST FDG-PET Imaging Hepatic, abdominal and pelvic metastases

CT 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- 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 TUMORS

• 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 CONSIDERATIONS • 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 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 MESYLATE 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 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

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MECHANISM OF ACTION Im a tin ibm e sy la te o c c u p ie sth eA T P b in d in gp o c ke to f th eK ITk in a s e d o m a in T h isp re v e n ts s u b s tra te p h o sp h o ry la tio n s ig n a lin g Ala c ko fs ig n a lin g in h ib itsp ro life ra tio n a n ds u rv iv a l

a n d

•

TYROSINE KINASE INHIBITORS MOLECULARLY TARGETED THERAPY ~ 9 0 % o f G IS T h a v e a n o n c o g e n ic m u ta tio n o f K IT o r

PDGFRA • M u ta tio n s o c c u r e a rly in G IS T d e v e lo p m e n t

– K IT m utatio ns a re d ete cta b le in inc id e≤n1tac m l tu m o rs – P a tie n ts w ith g e rm lin e K IT m utatio ns de v e lo p m u ltip le G IS T – K IT m utatio ns p rec e d e c yto g e ne tic c ha n g es in G IS T d e v e lo p m e nt

• Im a tin ib m e s y la t e is a s p e c ific in h ib it o r o f K IT tyr o s in e k in a s e a c tivit y a n d b lo c-m k se Kd ia I Tte d d o w n s tre a m s ig n a lin g

SCIENTIFIC RATIONALE FOR IMATINIB MESYLATE IN THE TREATMENT OF GIST

• Im a tinib m es yla te is an-mA im TPe tic TK I

of the K IT, B-Ac rbl, a n d P D G F R A /B re c ep to rs • In ce ll c u ltu re e xp e rim e nts , im a tin ib m es yla te effe ctiv ely inh ibits ac tiv a te d K IT , re s ultin g in d e a th of G IS T c ells in c ultu re

JEJUNAL STROMAL TUMOR WITH MUCOSAL ULCERATION

INTRAOPERATIVE VIEWJEJUNAL STROMAL TUMOR

RESECTED SPECIMEN TUMOR WITH A SEGMENT OF JEJUNUM

RESECTED SPECIMEN

MACROSCOPIC TUMORAL ASPECT

ENDOSCOPIC VIEW TAKEN BY SWOLLEN VIDEOCAPSULE

PROTRUSIVE ENDOLUMINAL TUMOR OF THE JEJUNAL WALL SMALL MUCOSAL LACERATION RESPONSIBLE FOR HDI

DOUBLE CONTRAST FOLLOW-THROUGH

DOUBLE CONTRAST FOLLOW- THROUGH

USS of the UPPER ABDOMEN

SMALL BOWEL DIVERTICULOSIS Duodenal diverticula- 90% are asymptomatic 70% -periampullary region- cholangitis, pancreatitis, CBD stones Jejunal diverticula-rare, may cause obstruction, bleeding, perforation, bacterial overgrowth within the diverticulum Meckel’s diverticulum- within 40 cm. of the ileocecal valve Meckel’s diverticulum may cause bleeding, obstruction, acute inflammation TREATMENT- resection with enteroraphy

ACUTE APPENCITIS Commonest condition requiring acute abdominal surgery The peak incidence in the 2nd-3rd decades Etiology: – Obstruction of the lumen (fecaliths, worms, cecal cancer) – Persistent appendiceal secretions, distention with inflammation, bacterial overgrowth, ischemia, gangrene, perforation

ACUTE APPENDICITIS DIAGNOSIS History 1-12 h. of digestive symptoms Symptoms: RIF pain, anorexia, nausea, vomiting Physical signs: fever, tachycardia, RIF guarding, rebound tenderness, Rowsig’s sign, psoas sign Lab.tests: WBC elevated, predominance of neutrophils

ACUTE APPENDICITIS COMPLICATIONS IF LEFT UNTREATED

Perforation with localized peritonitis Appendiceal inflammatory mass Appendiceal abscess +/- diffuse peritonitis Septicemia Multiple Systemic Organ Failure

ACUTE APPENDICITIS DIFFERENTIAL DIAGNOSIS

Mesenteric lymphadenitis Chrohn’s disease- flare up Pelvic inflammatory disease Ruptures ovarian cyst Ureteric calculi, UTI Sigmoid diverticulitis

ACUTE APPENDICITIS TREATMENT Broad-spectrum antibiotics Iv. fluids, nil by mouth more than 6 h. preoperatively. Laparoscopic / open appendicectomy Drainage depending on the severity of the lesion