GIT

Exam questions:

Lesions of the oral cavity
Salivary gland diseases
Esophageal lesions
Gastric lesions - review
Gastritis
Peptic ulcer
Small bowel lesions - review
Crohn's disease
Malabsorption syndrome
Small bowel obstruction
Large bowel lesions - review
Hirschprung's disease
Enterocolitis
Lesions of the appendix
Lesions of the peritoneum - review
Herniae
Tumors of the oral cavity and nasopharynx
Salivary gland tumors
Esophageal tumors
Gastric tumors
Small intestine tumors
Large intestine tumors


Lesions of the oral cavity:
affecting:
	soft tissues
	teeth
Ulcerative and inflammatory lesions:
Aphtous ulcers (Canker sores) - common, small, painful, shallow ulcers. Singly or in groups. Soft palate, buccolabial mucosa, floor of the mouth, lateral borders of the tongue. First two decades of life. Triggered - stress, fever, certain foods. Self-limited,  recurs!

Herpesvirus - common, HSV-1, person-to-person, kissing. Virus persists within ganglia (trigeminal), solitary or multiple. Localization - lips. Cold sores, fever blisters. After blister rupture - painful ulcers, heals, recurrences common. Infected cells ballooned, containing viral inclusions. Tzanck test for HSV infection (scraping of the sore, staining, microscopy).
HSV-1 in prepubescent or immunocompromised adult - multiple lesions, herpetic gingivostomatitis, viremia, encephalitis, keratoconjunctivitis, esophagitis.
HSV-2 - herpes genitalis, sexually transmitted

Fungal infections - Candida albicans, disease only if: diabetes mellitus, anemia, ATBs, glucocorticoids, immunodeficiency. Circumscribed plaques. It may spread into the esophagus (nasogastric tube), disseminated candidiasis (bloodstream).

AIDS:
Oral infections common - candidiasis, herpes, microbial infections. 
Kaposi's sarcoma - in 20% of patients - homo- or bisexual males.
Hairy leukoplakia - uncommon, only in HIV positive persons, "hairy" surface, epithelial thickening. Cause - Epstein-Barr virus

Leukoplakia:
Whitish, well defined patch or plaque - epidermal thickening or hyperkeratosis.
Older men - vermilion border of the lower lip, buccal mucosa, palates, floor of the mouth. Localized or multifocal. Hyperkeratosis, atypia, dysplasia, Ca in situ.
Tobacco - pipe smoking, alcohol abuse, irritant foods.
5-10% - malignant transformation to squamous cell carcinoma (common to less common: lip, tongue, floor of the mouth).
Diff. dg.:
Hairy leukoplakia - AIDS, does not turn to carcinoma.
Erythroplasia - red, velvety, granular, irregular borders, marked dysplasia, turns to Ca in 50%.

Oral cancers:
Squamous cell carcinomas in majority. Older age, risk factors - leukoplakia, erythroplasia, alcohol, tobacco, human papilloma viruses 16, 18, 11, irritation (weakly), Plummer-Vinson (?).
Three sites of origin:
1/vermilion border of the lateral margin of the lower lip
2/floor of the mouth
3/lateral borders of the tongue
Gross appearance - white to gray, circumscribed thickening, growing in an exophytic or endophytic (invasive) fashion. Moderately to well differentiated keratinizing tumor.
Spread to regional lymph nodes - rarely in lip Ca, 50% in tongue Ca, 60% Ca of the floor of the mouth. Remote metastases - thorax or abdomen - less common.
Symptoms - local pain, sometimes asymptomatic, 5-years survival - 90% lip Ca, 30% base of the tongue, floor of the mouth, pharynx.

Salivary glands:
Diseases mainly within parotid gland.
Sialoadenitis:
Viral, bacterial, autoimmune.
Mumps (viral) - edema of the parotid (or other major gland), self-limited, complication - orchitis, sterility.
Autoimmune sialoadenitis - bilateral - Sjoegren's syndrome - all salivary glands - xerostomia (dry mouth), dry eyes (keratokonjunctivitis sicca). Combination: salivary+lacrimal gland - eponym Mikulicz's syndrome.
Bacterial sialoadenitis - sialolithisis. (intersticial or abscesses, necrosis)

Salivary gland tumors:
80% within parotid gland, male:female ratio 1:1, 6th or 7th decade
70-80% parotid tumors are benign
only 50% other gland tumors benign!!!
Most common within parotid - pleomorphic adenoma, less frequent cystadenoma lymphomatosum (Warthin's tumor) - these two represent 3/4 of all parotid tumors.
Malignant tumors: 	malignant pleomorphic adenoma (de novo or in preexisting tumor)
			mucoepidermoid carcinoma
Pleomorphic adenoma (mixed tumor, myxochondroepithelioma) - most common, well demarcated, encapsulated. Up to 6 cm in diameter. Painless swelling, multiple projections through the capsule - recurrences (in 10%).
	Histology - heterogenity - epithelial islands, interstitial - myxoid, chondroid, rarely bone. Malignancy less common in the parotid (15%), submandibular (40%)
Warthin's tumor - only in the parotid gland. Small, encapsulated, cystic spaces lined by epithelium (two layers), adjacent lymphoid tissue with germinal centers. Recurrences in 10%. Malignant transformation does not exist (probably).


Esophagus:
From highly lethal Ca to bland esophagitis.
Dysphagia, heartburn, hematemesis, melena.

Anatomic and motor disorders:
Stenosis - adults, dysphagia, lower esophagus narrowing due to reflux and inflammation
Atresia and fistula - newborn with aspiration (absence of lumen), tracheoesophageal fistula (may be together) 
Mucosal webs - acquired mucosal membrane occluding the lumen
Diverticula - nocturnal regurgitation, acquired outpouching of the wall

Hiatal hernia:
Separation of the diaphragmatic crura and widening of the space between the muscular crura.
Two patterns:
	1/axial (sliding) hernia - 95 % of cases, protrusion of stomach through the diaphragm, bell-shaped
	2/paraesophageal (rolling) - separate portion of stomach, cause obscure
Heartburn, regurgitation of food, incompetence of sphincter. Obesity!
Complications - ulceration, bleeding, perforation.

Achalasia:
"Failure to relax" of lower esophageal sphincter in swallowing.
Manometric changes:
	1/aperistalsis
	2/partial or incomplete relaxation of the lower sphincter
	3/increased resting tone of the lower sphincter
Impaired arrangement of innervation.
Secondary - destruction of the myenteric plexus - Chagas' disease (Trypanosoma cruzi)
Progressive dilatation of proximal esophagus, inflammation, thickening, nocturnal regurgitation, young adults, childhood, risk of squamous Ca.

Laceration (Mallory-Weiss Syndrome):
Longitudinal tears - chronic alcoholics - inadequate relaxation of the musculature of lower sfincter during vomiting. Mucosal tear - bleeding, wall tear - ulcer, mediastinitis.

Varices:
Communication between intra-abdominal splanchnic circulation and the systemic venous circulation through the esophagus. Liver cirrhosis - portal hypertension. 2/3 of all cirrhotic patients. Massive hemorrhage, 40% die during first episode, one half occurs within one year, survival the same like first attack.

Esophagitis:
Prolonged gastric intubation, uremia, irritant foods, alcohol, smoking, radiation, chemotherapy. Higher incidence in northern Iran and China. Mild - hyperemia, severe - ulceration.
Reflux esophagitis:
	1/eosinophils
	2/basal zone hyperplasia
	3/elongation of lamina propria papillae
Heartburn, regurgitation, sour brash, chest pain (mimicking MI), bleeding, Barrett.

Barrett's esophagus:
Long-lasting reflux, replacement of the normal distal squamous mucosa by abnormal metaplastic columnar epithelium with goblet cells (healing from stem cells). Low pH - ulcers, 30-40 fold increased risk of adenoCa.
Red, velvety mucosa extending up from gastroesophageal junction or isolated islands in the distal esophagus.



Esophageal carcinoma:
Benign tumors - papilloma, leiomyoma, etc.

Malignant tumors - squamous cell Ca
Risk factors:
esophagitis, achalasia, Plummer-Vinson sy (esophageal webs, microcytic hypochromic anemia, atrophic glossitis)
Life style - alcohol, tobacco
Dietary - vitamin deficiency, trace metals, fungal contamination, nitrits/nitrosamines
Genetic - tylosis (hyperkeratosis of palms and soles) - northern Iran
Barrett - adenoCa

Long prodromes, dysplastic changes.
Grossly:
1/polypoid protrusions
2/ulcerative lesions
3/diffuse rigidity of the wall

AdenoCa:
Barrett - distal esophagus (Barrett arises from multipotential cells)


Weight loss, anorexia, fatigue, pain related to swallowing. 
Biopsy, surgery


Stomach:
From bland gastritis to carcinoma.
Congenital . pyloric stenosis, diaphragmatic hernia, gastric heterotopia (esophagus, small intestine - Meckel).
Heartburn, vague pain, hematemesis, melena.

Gastritis:
Inflammation of gastric mucosa.
Acute or chronic.

Chronic gastritis:
More frequent than acute, leads to atrophy or metaplasia.
Main cause - Helicobacter pylori, probably acquired in childhood, persists for decades.
3,5 x 0,5 micromm. Bacterial enzymes+toxins+noxious chemicals from recruited neutrophils.Intestinal metaplasia - dysplasia. Proliferation of lymphoid tissue - ML.
Never achlorhydria, only hypochlorhydria.

Autoimmune gastritis - antibodies against gastric gland paretal cells - gland destruction, atrophy - loss of acids+intrinsic factor - pernicious anemia. Very common in Scandinavia. Hypo- or achlorhydria + hypergastrinemia.

 
Acute gastritis:
Mucosal inflammatory process of transient nature (usually).
Causes - aspirin, alcohol, smoking, chemotherapy, uremia, infections (salmonellosis), stress, ischemia - shock, suicide (acids or alkali), trauma (intubation), distal gastrectomy (biliary reflux).
Broad spectrum of severity. 
Acute erosive gastritis. Nausea, vomiting, hematemesis (alcoholics).

Gastric ulceration:
Deeper than muscularis mucosae - contrast to erosions.

Peptic ulcers:
Usually chronic, more in duodenum than in stomach (4:1).
Middle age or older. Duodenal - alcoholic cirrhosis, right heart failure, chronic renal failure.
Helicobacter pylori - 70% gastric ulcers, 100%.
Only 10-20% patients with Helicobacter pylori develop peptic ulcer. Unknown interactions.
Zollinger-Ellison sy - hypergastrinemia. Cigarette smoking, alcohol. corticosteroids, stress.
Chronic ulcers - several cm in diameter. Elevated walls - "U" shaped, radial mucosal walls. Anterior or posterior wall of first portion of duodenum, lesser curvature of stomach. Gastritis is almost always associated.
Complications - penetration - to omentum, liver, pancreas. Perforation - peritonitis, Bleeding - melena, exsanguination.
Microscopy - 4 leyers - debris, active inflammation, granulation tissue, fibrous scar.
Symptoms - burning and boring pain, weight loss, hemorrhage. Pain is worse at night, relived by alakalis or food.
Untreated ulcer require 15 years for healing. Therapy - alkalic substances, ATB (Helicobacter), vagotomy, surgical resection (nowadays rarer).

Acute ulcers:
Stress!!! Mainly in stomach, rerely in duodenum.
Causes - trauma, stress, surgical injury of CNS, extensive burns, gastric irritant drugs.
Small - up to 1 cm, anywhere in the stomach, usually multiple. Adjacent mucosa without inflammation.


Tumors:
Epithelial tumors predominate.
Polyps:
1/hyperplastic - 80 - 85% - are not true neoplasms 
2/fundic gland polyps - 10% - dilated glands
3/adenomatous - 5% - true neoplasms
All in chronic gastritis.

Gastric carcinoma:
AdenoCa (90-95%), carcinoids (3-4%), and mesenchymal tumors (2%).
Geographical incidence - most common in Japan, Hungary.
AdenoCa - two forms- 	1/intestinal type - from intestinal metaplasia - chronic gastritis - male predominance - nitrites, smoked foods, pickled vegetables, salt intake, Helicobacter pylori, pernicious anemia.
				2/diffuse form - in younger, directly from gastric glands - risk factors unknown.

Localization- pylorus, antrum, cardia, remainder of the body and fundus.
Early cancer - mucosa, submucosa.
Morphology:
1/exophytic
2/flat or depressed
3/excavated - ulcerative lesions
Leather bottle stomach - scirhous carcinoma (linitis plastica).
Histology:
1/intestinal type
2/diffuse - "signet ring" cells.
Metastasis - regional lymph nodes, supraclavicular node (Virchow's). Krukenberg tumor.
Symptoms - abdominal discomfort, weight loss, pain.
Therapy - surgical removal.


Small and large intestines:
Small intestines developmental anomalies:
Atresia - non-developed lumen - segmental
Stenosis - narrowing - segmental 
Duplication - saccular or tubular structures
Meckel's diverticulum - failure of involution of omphalomesenteric duct, 3-4 cm long, distal ileum, asymptomatic, sometimes bacterial overgrowth that depletes vitamin B12 - pernicious anemia, gastric metaplasia, islands of pancreatic tissue
Omphalocele - defect of the periumbilical abdominal wall - membranous sac

Large intestines anomalies:
Malrotation - cecum in left upper abdomen (confusing appendicitis), Hirschprung disease - megacolon

Hirschprung disease - congenital megacolon:
Congenital distention of the lumen (5-6 cm), impaired migration of neural crest-derived cells, cells are arrested before reaching the anus - functional obstruction - proximal dilatation. Segment of rectum and sigmoideum are usually aganglionic. 1/5 of cases - longer segment, rarely - the whole colon. Males predominate (4:1). Sometimes extreme dilatation (15-20 cm in diam.) - ulcers, stercoral peritonitis.
Symptoms -  vomiting in 48 to 72 hours. Surgical resection of aganglionic segment (frozens).
Acquired megacolon:
1/Chagas's disease - trypanosomes destroy the plexus
2/obstruction by the tumor
3/toxic megacolon
4/functional psychosomatic disorder

Vascular disorders:
Ischemic bowel disease:
Acute occlusion - infarction (celiac, superior, and inferior artery). Block of end-arteries - transmural necrosis (the whole thickeness), mural (mucosa+submucosa), mucosal (not deeper than muscularis mucosae).
Sometimes venous obstruction (thrombosis) - hemorrhagic infarsation.
Conditions - 1/arterial thrombosis - AS, vasculitis, surgical accidents, oral contraceptives.
		2/arterial embolism
		3/venous thrombosis
		4/non-occlusive ischemia - shock, dehydration, cardiac failure
Transmural infarction - dark red hemorrhagic, gangrene (bacteria), perforation
Mural and mucosal - multifocal, usually AS, ulcerations, inflammation, pseudomembrane (inflammatory fibrin-containing exsudate)
Symptoms - usually in older patients, transmural - severe pain, bloody diarrhea, may progress to shock, high mortality
Mural and mucosal - abdominal distention, bleeding, pain, may be fatal but may heal

Angiodysplasia:
Tortuous dilatation of mucosal and submucosal vessels - cecum, 6th decade, bleeding. Sometimes as part of hereditary hemorrhagic teleangiectasia (Osler-Weber-Rendu sy). More often - isolated lesions, cause - mechanical factors.

Hemorrhoids:
Venous dilatation - rectum and anus, after the age of 50, pregnancy, obstipation, liver cirrhosis.
Internal h. - above anorectal line, rectal mucosa, external h. - below, lined by anal mucosa.
Complications - bleeding, prolaps, thrombosis.

Diarrheal diseases:
Diarrhea and dysentery:
Diarrhea - definition difficult, stool fluidity! Extreme - 14 litres. Pain, urgency, incontinence, perianal discomfort.
Dysentery - low-volume, painful, bloody diarrhea.
Secretory diarrhea - fluid isotonic with plasma, persists during fasting
Osmotic d. - excessive osmotic tonus, abate during fasting
Exsudative diseases - purulent, bloody stools, persists during fasting
Malabsorption - voluminous stool, unabsorbed nutritients, usually abates during fasting
Deranged motility - other causes of diarrhea must be excluded
Major causes:
Secretory diarrhea - infectious (rotavirus, Norwalk virus, enteric adenoviruses), enterotoxin-mediated Vibrio cholerae, Escherichia coli, Clostridium perfringens, neoplastic (serotonin production - carcinoid), excesive saxative use.
Osmotic diarrhea - lactulose therapy, antacids.
Exsudative diseases - infection - destruction of the epithelium - Shigella, Salmonella, Campylobacter, Entamoeba histolytica. 
Malabsorption - defective intraluminal digestion, defective mucosal cell absorption, reduced small intestinal surface.

Viral gastroenteritis (gastritis less pronounced in a case of all gastroenteric cases):
Rotavirus - fecal-oral, children, Norwalk virus - older children, adults, other viruses (adenovirus, calcivirus, astrovirus)

Bacterial enterocolitis:
Toxins (Staphylococcus aureus, Vibrio, Clostridium perfringens,, Clostridium botulinum), infection by organisms which proliferate within the gut, infection by enteroinvasive organisms which destroy epithelium. Table 15-7, page 495 (Robbins, 6th ed.). Damage of surface epithelium, edema, hyperemia, neutrophilic infiltration.
Salmonella (typhi, enteritidis) - typhi - typhoid fever - bacteremia, splenomegaly (may rupture), focal liver necrosis, ulceration of Peyer's patches, shock. Gallbladder colonization.
Shigella - distal colon.
Campylobacter jejuni - superficial ulcers.Yersinia enterocolitica - lymph node granulomas (lymphadentis mesenterialis).
Vibrio cholerae - small intestine, mucus depleted crypts.
Clostridium difficile - pseudomembranous colitis.
Clostrdium perfringens - severe necritizing enterocolitis with perforation (pigbel)
Symptoms - ingestion of toxins - matter of hours - explosive diarrhea, C. botulinum - fatal. Infection with enteric pathogen - hours to days - diarrhea, dehydration (traveler's diarrhea, Montezuma's revenge)
Neonates - necrotizing enterocolitis - functional immaturity of the neonatal gut.

Protozoal infection:
Entamoeba histolytica - fecal-oral spread, flask-shaped ulcers, little infiltrate, penetration to portal vessels, liver abscesses (more than 10 cm in diam.)
Giardia lamblia (Dušan Lambl) - contamined water, does not invade, villous blunting (otupění), malabsorption diarrhea.

Malabsorption syndromes:
Impaired absorption of fats, fat-soluble vitamins, protein, carbohydrates, electrolytes, minerals, and water due to:
1/intraluminal digestion - mouth (saliva), stomach (peptic), small intestine (pancreatic)
2/terminal digestion - hydrolysis - brush border
3/trasepithelial transport
Most common - due to pancreatitis, celiac sprue, and Crohn's disease.
Table 15-8, page 497

Pancreatic insufficiency:
Chronic pancreatitis, cystic fibrosis. Bacterial overgrowth - osmotic diarrhea, steatorrhea.

Lactose intolerance - inherited disaccharidase deficiency - milk intolerance.
Abetalipoproteinemia - unable to transport lipids.
Gluten-sensitive enteropathy:
= celiac sprue, non-infectious, reduction of absorptive surface, sensitivity to gluten (grains of wheat, oat, barley, rye) containing gliandin. Accumulation of B-cells within mucosa, epithelial damage.
Gliandin cross-reacts with adenovirus. Long-term risk of ML, GIT and breast Ca.

Tropical sprue - infection (unknown), diffuse enteritis, ATB treatment, villus flattening.
Whipple's disease - intestine, CNS, joints. Macrophages laden by Gram+ actinomycete Tropheryma whippelii. ATB treatment, males, 4-5th decade.

Idiopathic inflammatory bowel disease:
Crohn's disease - sharply segmental transmural fibrosis and thickening, usually terminal ileum, sometimes "skips", anywhere in GIT (systemic disease - accompanied by iritis, uveitis, sacroilitis, polyarthritis, sclerosing cholangoitis).
Any age but 2nd - 3rd decade preferred.
Sharply delimited, transmural, mucosal damage, granulomas, fissuring and fistulae. Aphtous ulcers in mucosa, longitudinal, mucosal inflammation, granulomas, extension of serosal fat (creeping fat), dysplastic changes, higher risk of Ca.
Symptoms - non-characteristic - pain, fever, sometimes bleeding, remissions, relapses.
Complications - fistulae to other bowel loops, urinary bladder, vagina, skin, abdominal abscesses, intestinal strictures.

Ulcerative colitis - limited to the mucosa and submucosa. Starts in rectum, extends proximally, sometimes the whole colon. Systemic disease - migratory polyarthritis, uveitis, sclerosing cholangoitis.
Granulomas are absent, skip lesions absent, little fibrosis, greater risk of Ca than Crohn.
Any age, peak 20-25 years.
Rectum+rectosigmoideum - 80%, entire colon 10%. Bleeding, edema, inflammatory pseudopolyps, ulcers - longitudinal, sometimes gangrene, mucosal atrophy. Diffuse inflammatory infiltrate, crypt abscesses. After ulcer healing - submucosal fibrosis. Dysplastic changes, high risk of Ca (duration of disease, extent of disease play a role).
Symptoms - pain, bloody mucosal diarrhea, than asymptomatic for months to decades. Cramps, tenesmus, weight loss. Extraintestinal manifestations - migratory polyarthritis. Dg - endoscopy, biopsy. Carcinoma!!!

Colonic diverticulosis (blind pouch leading off the alimentary tract):
Congenital - all three layers - Meckel.
Most - acquired - anywhere in GIT, mostly in colon. Teniae, where nerves and vessels penetrate internal (circular) muscular layer - defects are created.
Older age, Western countries. Low fiber diet!
Two factors:
1/peristaltic contractions - elevation of pressure
2/focal defects of muscular wall
Appearance - up to 1 cm, usually sigmoid, adjacent to teniae, thin-walled.
Complications - inflammation - diverticulitis, perforation - peritonitis, adhesions.
Symptoms - asymptomatic, cramping, discomfort, diverticulitis - pain, abscess formation. Treatment - high-fiber diet, diverticulitis - surgery.

Bowel obstruction:
Table 15-10, page 504, Robbins.
Hernias - protrusion of pouchlike, serosa-lined sac of peritoneum - hernial sac. Inguinal, femoral, umbilical canal, surgical scars. Retroperitoneal hernia - Treitz ligament. Segments of viscera trapped, incarceration, ileus, strangulation. 
Intussusception - proximal segment to distal.
Volvulus - twisting of the loops or other structures (ovary) - small bowel usually - obstruction, infarction.

Tumors:
Highest incidence of colorectal Ca in the Czech Republic.
Mainly large intestine. Table 15-11, Robbins page 505
Polyp - typical, sessile, pedunculated; non-neoplastic - inflammatory (hyperplastic), adenomatous polyps.

Non-neoplastic polyps - increase with age, 90% of all polyps, hyperplastic - small (up to 5 mm), singly or multiple, no malignant potential!
Juvenile polyps - hamartomatous, cystic glands, children younger than 5 years. In adults - retention polyps - long stalk, occur in rectum.
Peutz-Jeghers polyps - hamartomatous - smooth muscle within mucosal stroma.

Adenomas:
Small to large, large intestine, dysplastic changes, all adenoCa arise from adenomas.
Three types:
1/tubular
2/villous
3/tubulovillous
Tubular - most common, sometimes pedunculated, branching glands, level of dysplasia must be determined from biopsy, sometimes intramucosal Ca, invasive - ingrowth into the stalk. Villous - large, sessile - older persons, colorectal, rectal, up to 10 cm in diam., more dangerous (40% from villous a. larger than 4 cm). Tubulovillous - admixture.
Risk of Ca - size, histology,severity of dysplasia.
Symptoms - asymtomatic, occult bleeding, bleeding, anemia. Polyp in Vater's ampulla - biliary obstruction. All adenomas potentially malignant.

Familial polyposis syndromes:
Autosomal dominant, familial adenomatous polyposis (FAP) - Gardner sy - more than 100 (it is the must). Most of them are tubullar adenomas. Risk of Ca - 100% by mid life.
Hereditary nonpolyposis colorectal cancer (HNPCC) - autosomal dominant (Lynch's sy) - high ris of colorectal Ca and endometrial Ca.

Colorectal carcinoma:
Large intestine (98%), 6 - 7th decade. Higher risk - adenomas, ulcerative colitis. Males 20% more than females. High in USA and Europe, low in India, South America, Africa. Japan - icreasing, mainly gastric.
Dietary causes:
1/low-fiber
2/high content of refined carbohydrates
3/high content of fat (from meat) - suspected synthesis of cholesterol and bile acids by the liver
4/low vitamin A, C, and E
Colorectal carcinogenesis - Gardner's sy - study of chromosome 5q21 - tumor supressor gene identified. HNPCC (hereditary nonpolyposis colorectal cancer) - chromososmes 2p22, 3p21, 2q31-33, 7p22 - human mismatch repair genes studied. Methylation abnormalities - loss of methyl groups in DNA. K-ras gene - activated oncogene in adenomas and Ca - mutated in 50% of Ca. Multi-hit concept of colon cancer carcinogenesis, cumulation of risk factors.

Distribution of Ca - proximal colon - polypoid, fungating mass. Colorectal - circular, stenosing. Both penetrate the wall into the serosal surface. Well to poor differentiation. Mucin production.
Symptoms - for long time silent, fatigue, iron deficiency anemia. Left sided - bleeding, cramping. Colorectal - stenosis. Metastasizing - regional lymph nodes, liver, lungs, bones. 
Detection - occult bleeding test, colonoscopy, biopsy, CT - spread (metastases), elevated CEA - little diagnostic value - tumor must be large (and positive in liver cirrhosis, etc.). Therapy - surgery.

Small intestinal tumors:
Only 3-6% of GIT tumors.
AdenoCa - unusual, circular growth - duodenum (ampula), lymph nodes spread.
Carcinoid - producing hormons, serotonin, derived from neuroendocrine cells. Potentially malignant, local infiltrative growth, metastases rare. Small bowel, appendix, rectum.
Within the mucosa, yellow-tan, desmoplasia. Mitoses almost absent. Asympthomatic, hormones metabolized in liver. Carcionid sy - (cutaneous flushes, diarrhea, asthma, systemic fibrosis - pulmonic+tricuspid valve) - primary hepatic carcionid or hepatic metastases.
GIT malignant lymphoma - usually non-Hodgkin, MALToma, H. pylori!

Appendix:
Acute appenicitis - acute abdomen. oxyuris vermicularis.
Mucocele - dilatation of the lumen by mucus - non-tumorous obstruction (fecalith) - mucosal atrophy. Rarely mucocele ruptures.

Appendical tumors:
Carcinoids. 
Mucinous cystadenoma, cystadenoCa. Pseudomyxoma peritonei - mucus+tumorous cells, implantation metastasis.