1. PATHOLOGY OF SMALL & LARGE INTESTINE DIVERTICULAR DISEASE
Diverticulum= blind pouch leading off the alimentary tract, lined by mucosa, communicating with gut lumen
Acquired >> congenital (e.g. Meckel’s)
May arise anywhere in GIT; colon is the most common site
Two main factors:
1) Weakness in the wall: defects at site of bv entry; congenital weakness (e.g. Marfan’s syndrome)
2) Increased peristalsis and intra-luminal pressure: hard stools due to low-fiber diet results in exaggerated peristaltic contractions

3. PATHOLOGY OF COLONIC DIVERTICULOSIS
Colonic diverticulosis is common in the West (50% of adults >60 yrs); associated with low-fiber diet
Multiple small cm
Sigmoid colon is involved in 95% of patients
Gross examination: Prominent taeniae coli & circular muscle bundles due to muscular hypertrophy; outpouching may be visible from serosal surface
Histology: sacs with thin wall made of mucosa & submucosa surrounded by fat or intact peritoneum

4. CLINICAL FEATURES OF COLONIC DIVERTICULOSIS
Usually asymptomatic
Intermittent cramping or continuous LLQ discomfort, sensation of incomplete emptying of rectum
Complications:
Diverticulitis: accentuates symptoms, tenderness, fever
Peridiverticulitis, perforation, abscess or fistula
Fistula formation
Bleeding
Rx: High-fiber diet; surgery

5. PATHOLOGY OF SMALL & LARGE INTESTINE BOWEL OBSTRUCTION
May occur at any level, but is more frequent in small intestine
May be acute or chronic
Clinical features: abdominal distension (+/- pain) , followed by vomiting, then constipation
May present at birth, during infancy, childhood or adulthood
Obstruction may be in the lumen, wall or extramural
Tumors and infarction account for 10-15% of small bowel obstruction
Hernias, intestinal adhesions, intussusception, and volvulus account for 80% of cases

7. CLASSIFICATION OF BOWEL OBSTRUCTION
Mechanical:
Congenital: strictures, atresias, bands, imperforate anus, meconium in cystic fibrosis
Infants: hernias, intussusception
Adults: hernias, adhesions, tumors, inflammatory strictures, obstructive gallstones, fecaliths, foreign bodies, volvulus
Functional:
Paralytic ileus: electrolyte imbalance, neural injury, or reflex atony secondary to peritonitis
bowel infarction,
myopathies & neuropathathies (e.g. Hirschsprung’s)

8. BOWEL OBSTRUCTION HERNIAS
Weakness or defect in wall of peritoneal cavity with protrusion of a serosa-lined sac of peritoneum
Inguinal & femoral canals, umbilicus & surgical scars
Segments of viscera may protrude & become entrapped, mostly in inguinal hernias
If small bowel is involved, partial or complete obstruction of its lumen may follow
Incarceration: permenant trapping of hernial sac contents due to venous stasis & edema
Strangulation: Venous & arterial supply to entrapped viscus is compromised leading to infarction or gangrene

9. BOWEL OBSTRUCTION INTESTINAL ADHESIONS
Due to localized or generalized peritonitis secondary to:
Surgical procedures
Infection
Endometriosis
Rarely due to congenital fibrous bands
May result in intestinal obstruction, incarceration and strangulation
Fibrous bridges which develop between bowel segments creating closed loops through which viscera may slide & become entrapped (internal hernias)

10. BOWEL OBSTRUCTION INTUSSESCEPTION
Uncommon disorder where a segment of small intestine, constricted by a a wave of peristalsis, suddenly becomes telescoped into the immediately distal segment of bowel
Intussusceptum: trapped bowel segment
Intussuscipiens: bowel segment which envelops it
Mostly in infants & children of unknown pathogenesis
In adults, an intraluminal tumor may act as point of traction, pulling along a segment of bowel
Intestinal obstruction
Intestinal infarction due to trapping of mesenteric blood vessels

11. INTUSSESCEPTION

12. BOWEL OBSTRUCTION VOLVULUS
Complete twisting of a loop of bowel about its mesenteric base of attachment
Mostly in small intestine; large intestine especially sigmoid & cecum, and other structures (e.g. ovary) may be involved
Constriction of venous outflow &/or arterial supply
Intestinal obstruction and infarction
Uncommon disorder, occuring in all ages when an intestinal segment becomes longer & the mesentary narrower
May be caused by colon malrotation & peritoneal bands

13. SMALL & LARGE INTESTINE TUMORS
Colonic tumors are much more common than small intestinal tumors
May arise from any layer of GIT wall (mucosa, submucosa, muscularis or serosa); most are of epithelial origin
The majority are benign; however, colonic cancers are a major cause of morbidity & mortality
Clinical presentation:
Asymptomatic; incidental finding
Blood per rectum; anemia
Bowel obstruction

14. INTESTINAL TUMORS Benign: Malignant: Stromal tumors
Hyperplastic & adenomatous polyps
Lipomas
Malignant:
Adenocarcinoma
Carcinoid tumors
Lymphoma
Sarcoma

15. PATHOLOGY OF SMALL & LARGE INTESTINE CARCINOID TUMORS
Tumors of neuroendocrine cells, which are widely distributed cells of epithelial stem cell origin capable of producing a variety of bioactive compounds
Tumors may produce multiple compounds or a predominant product, causing a clinical syndrome such as gastrinoma, insulinoma ...
Tumors arrise in GIT, lung, biliary tree & pancreas
50% of small intestinal & 2% of colonic tumors
Any age, peak incidence in 6th decade
Carcinoids are well differentiated tumors that are potentially malignant tumors and may metastasize

16. CLINICAL FEATURES OF CARCINOID TUMORS
Sites: appendix>small intestine (ileum)>rectum> stomach>colon
Most are asymptomatic (particularly appendix)
May cause local symptoms (angulation or obstrcution of small intestine)
Secretory products may produce a variety of endocrinopathies, e.g. Zollinger-Ellison syndrome, Cushing’s syndrome, hyperinsulinism
Carcinoid syndrome: 1% of patients & 20% of those with widespread metastasis; due to serotonin secretion; vasomotor disturbances, intestinal hypermotility, hepatomegaly and systemic fibrosis

17. PATHOLOGY OF CARCINOID TUMORS
Gross: usually small tumors, rarely >3 cm, forming an intramural or submucosal yellow-tan firm elevation or polypoid lesion
Histology: monomorphous population of cells with scant granular cytoplasm & round nuclei. Neoplastic cells form islands, nests, strands or glands. Intact or ulcerated overlying mucosa.
May be multicentric (stomach, ileum)
May be localized or have local spread &/or metastasis to lymph nodes or more distant sites, particularly liver

21. CLINICAL BEHAVIOUR OF CARCINOID TUMORS
Clinical behaviour is difficult to predict from histologic features
Behaviour but generally depends on:
1) Size: >2 cm and those invading >1/2 wall thickness
2) Site: appendiceal & rectal carcinoids almost never metastasize
5 years survival rate is excellent: 90%
5 years survival rate for small intestinal tumors with liver metastasis: 50%
Widespread disease usually causes death

22. SMALL INTESTINAL ADENOCARCINOMA
Most arise in duodenum, including ampulla of Vater
Polypoid fungating tumor growing in a napkin-ring encircling pattern
Early on, tumor is asymptomatic
Signs & symptoms usually appear late, when tumor has already penetrated bowel wall into mesentery, other bowel segments or spread to LN, or metastasize to liver or more widely
c/o symptoms of abdominal obstruction (pain, nausea, vomiting, and weight loss)
5 yrs survival with wide en bloc excision: 70%

24. SMALL & LARGE INTESTINE POLYPS
Polyp= a tumorous mass protruding into the lumen of the gut; may be pedunculated or sessile
Major types:
Non-neoplastic polyps: about 90% of polyps; formed as a result of abnormal mucosal maturation, inflammation or architecture
Hyperplastic polyps
Hamartomatous polyps
Inflammatory polyps
Neoplastic polyps: formed as a result of epithelial proliferation and dysplasia, i.e. pre-cancerous
Adenomatous polyps

26. INTESTINAL POLYPS HYPERPLASTIC POLYPS
Majority of polyps
Site: mostly in colon, >50% in rectosigmoid
Patients: increase in frequency with age
Appearance: Most are small <5 mm, nipple-like protrusion; multiple or single
Pathology: histologically consist of abundant crypts lined by well-differentiated goblet or absorptive epithelial cells, seperated by scant lamina propria
Asymptomatic or blood &/or mucus per rectum
No malignant potential

28. INTESTINAL POLYPS HAMA‏RTOMATOUS POLYPS
Juvenile polyps:
Hamartomatous proliferation of lamina propria surrounding cystically dilated glands
Patients: usually <5 yrs; in adults called “retention polyp”
Appearance:1-3 cm in children; smaller in adults
Single rounded or lobulated, +/- stalk
Bleeding per rectum; stalk may twist and undergo painful infarction
No malignant potential

29. INTESTINAL POLYPS HAMA‏RTOMATOUS POLYPS
Peutz-Jeghers polyps:
Rare autosomal dominant syndrome, characterized by GIT polyps, melanotic mucosal and cutaneous pigmentation around lips, oral mucosa, face, genitalia & palmar surfaces of hands
Site: polyps may occur in stomach (25%), colon (30%) and small intestine (100%)
Appearance: large peduculated lobulated polyps
Pathology: branching framework of connective tissue & smooth muscle
Polyps have no malignant potential, but PJS patients have increased risk of developing carcinoma of pancreas, breast, lung, ovary & uterus

31. INTESTINAL POLYPS A‏DENOMATOUS POLYPS
Vast majority of adenomas arise in colon
Variable in size; pedunculated or sessile
Results from epithelial proliferation and dysplasia, which may range from mild to carcinoma in situ
Three architectural types:
1) Tubular adenoma
2) Villous adenoma
3) Tubulovillous adenoma
Risk of malignant transformation depends on:
Polyp size: <1 cm (v. rare); 1-2 cm (10%); >2 cm (45%)
Histologic architecture: proportion of villous component
Severity of dysplasia

36. INTESTINAL POLYPS A‏DENOMATOUS POLYPS
Tubulovillous adenoma: 5-10% of adenomatous polyps; mixture of tubular & villous (20-50%) areas; intermediate in frequency of having a stalk, size, degree of dysplasia & risk of carcinoma
Clinical features: 20-30% are <40 yrs; 50% after 60
Small polyps: asymptomatic
Occult bleeding, anemia, hypoproteinemia & hypokalemia
Intestinal obstruction or biliary obstruction
Rx: Most are cured by adequate endoscopic excision
Px: Annual endoscopic follow-up

37. ADENOMATOUS POLYPS TUBULAR ADENOMA VILLOUS ADENOMA
>85% of adenomas
Majority in distal colon; 50% in rectosigmoid
Most are small (few mm-2 cm) with a stalk (-2 cm)
Histology shows neoplastic epithelium forming glands & tubules
Variable degrees of dysplasia to CIS
Invasive carcinoma rare
1% of adenomas
Rectum & rectosigmoid 75%, followed by cecum & ascending colon
Sessile ranging from cm (most are 1-3 cm)
Histology shows neoplastic cells forming villi (>50% villous)
Carcinoma in situ 10%
Invasive carcinoma 30%

38. INTESTINAL POLYPS FAMILIAL POLYPOSIS SYNDROMES
Familial adenomatous polyposis (FAP):
Rare autosomal dominant trait
Dx: at least 100 polyps (average 1000)
Most are tubular adenomatous polyps
Genetic defect of APC gene localized to chromosome 5q21
Risk of colon cancer: 100% at 30 years
Rx: Prophylactic colectomy
Gardner’s syndrome:
+ osteomas, epidermal cysts, fibromatosis, thyroid Ca..
Turcot’s syndrome:
+ CNS tumors (gliomas)

40. INTESTINAL POLYPS FAMILIAL POLYPOSIS SYNDROMES
Lynch’s syndrome:
aka: Hereditary nopolyposis colorectal cancer (HNPCC)
Autosomal dominant syndrome characterized by an increased risk of colorectal cancer and extra-intestinal cancer, particularly endometrial carcinoma
Multiple recurrent colorectal adenomatous polyps which present ar an early age
Mutations in any of 4 genes (MSH2, MLH1, PMS1 & PMS2) involved in DNA repair, located in chromo-somes 2, 3 & 7, resulting in microsatellite instability
Colonic carcinoma is typically located proximal to splenic flexure, often multiple, and not arising in preexisting adenomas

41. TUMORS OF LARGE INTESTINE COLORE‏CTAL ADENOCARCINOMA
More than 98% of colonic malignancies
Second most common cancer
Peak incidence yrs; <20% before age of 50 yrs
Wide geographic variation in incidence; more frequent in Western industrialized nations
Environmental dietary factors have been implicated:
Low unabsorbable vegetable fiber content
High refined crabohydrate content
High fat content
Low protective micronutrients content (vit. A, C & E)
Almost always arise in adenomatous polyps

42. COLORECTAL ADENOCARCINOMA THE ADENOMA-CARCINOMA SEQUENCE
Cumulative alterations in the genome lead to progressive increase size, dysplasia & invasive potential
“Multi-hit” concept for colon cancer carcniognesis:
First hit: germline or somatic mutations of cancer suppressor genes i.e. APC & mismatch repair genes
Second hit: Methylation abnormalities & inactivation of of normal alleles of APC & mismatch repair genes
Protooncogene mutation, e.g. K-ras at 12p12
Homozygous loss of addtional cancer suppressor genes, e.g. DCC at 18q21 and p53 at 17p13
Additional mutations of many genes will occur in carcinoma

44. PATHOLOGY & CLINICAL FEATURES OF COLORECTAL ADENOCARCINOMA
Majority are sporadic; 1-3% in patients with FAP or IBD
Mostly single; location is shifting to the right colon
Proximal colon: fungating polypoid tumors
Distal colon: annular encircling tumors (napkin-ring)
Tumors penetrate colonic wall layer into serosal surface
Histology range from well differentiated to undifferentiated; may be mucin-secreting
Asymptomatic for year
Right: fatigue, weakness, iron-deficiency anemia
Left: occult bleeding, change in bowel habit, discomfort
Dx: PE, lab, X-ray, endoscopy and biopsy

49. COLORECTAL ADENOCARCINOMA Modified Dukes’ (Astler-Coller) Staging System

50. TUMORS OF SMALL & LARGE INTESTINE INTESTINAL LYMPHOMA
The GIT is the most common extranodal location of lymphomas
May be primary or secondary
Primary GI lymphoma: no evidence of liver, spleen or bone marrow involvement at diagnosis
Adults, M=F, stomach>small intestine>colon
Classification similar to nodal lymphomas: MALTomas, large cell lymphoma, … etc.
Nonspecific symptoms
Rx: surgery, chemo- and radiotherapy
Px: better than nodal lymphomas