Tumuors of the SI and LI – January 9, 2007

Tumours of SI and LI
~ epithelial tumours of the intestine
~ primary neoplasms – colon and rectum
~ adenocarcinomas – main colorectal CA
~ SI – uncommon site for tumours (benign or malignant)

SI and LI Tumours
~ polyp – mass that protrudes into lumen of gut
~ can be pedunculated (has stalk) or sessile (no stalk)
~ form due to epithelial proliferation and dysplasia = adenomatous polyps or adenomas
~ true neoplastic lesions and precursor to carcinoma
~ oma – benign EXCEPT melanoma, meyloma, lymphoma
~ sarcoma – spread thru blood and is tissue in nature
~ carcinoma – spread thru lymph and is epithelial in nature

Non-neoplastic (Benign) Polyps

~ Juvenile, Peutz Jeghers
~ most are hyperplastic polyps
~ no malignant potential
~ usually on right side of colon
~ Juvenile polyps – hamartomatous proliferations
~ if in adults, called retention polyps
~ a mass resembling a tumor that represents anomalous development of tissue natural
to a part or organ rather than a true tumor
~ generally occur singly in rectum, usually no malignant potential

Adenomas (Neoplastic)
~ epithelial proliferation and dysplasia
~ neoplastic polyps
~ 3 subtypes:
~ 1) tubular adenomas – confined to the mucosa (intramucosal carcinoma) or
extending into submucosa (invasive carcinoma)
~ 2) villous adenomas – larger and more ominous
~ 3) tubulovillous adenomas – intermediate
~ maximum diameter is chief determinant of risk of adenoma  carcinoma

Familial Polyposis Syndromes

~ uncommon autosomal dominant disorder
~ familial adenomatous polyposis
~ risk of colonic cancer is almost 100% by midlife unless colectomy
~ Peutz-Jeghers polyps – uncommon hamartomatous
~ rare autosomal dominant
~ lots of melanin in mucosal and cutaneous areas
~ Cowden syndrome – hamartomatous polyps in GIT
~ increase risk of neoplasms of thyroid, breast, uterus, and skin

Colorectal Carcinoma
~ mainly adenocarcinomas
~ environmental factors, especially dietary practices
~ decreased fiber leads to decreased stool bulk, therefore increased bowel feces retention
and intestinal dysbiosis
~ potentially toxic oxidative byproducts of bacterial carb degradation
~ high fat intake enhances synthesis of cholesterol and bile acids by liver which is then
converted potential carcinogens by intestinal bacteria
~ potential pathogenesis: induction of apoptosis in tumour cells and inhibition of
angiogenesis, maybe inhibition of cyclooxygenase-2

Adeno-Carcinoma Sequence
~ 1) increased adenoma = increased colorectal CA
~ 2) adenoma and colorectal CA have similar distribution
~ 3) in biopsy carcinoma, see adenomatous tissue
~ 4) CA risk related to # of adenoma

Colorectal Carcinogenesis
~ 2 pathogenetically distinct pathways
~ 1) APC/β-catenin pathway – chromosome unstable and get accumulation of mutation of
oncogene or tumour suppressor gene
~ 2) DNA mismatch repair genes – lose ability to repair DNA-mismatch and the mutation
accumulates

Adenoma-Carcinoma Pathway
~ 1) loss of APC tumour suppressor
~ 2) mutate K-RAS – which prevents apoptosis
~ 3) 18q21 deletion – loss of CA suppressor gene
~ 4) loss of TP54 – loss of suppressor gene

SI Neoplasms
~ m/c benign tumours – stromal tumours
~ GIT stromal tumours have mutation affecting KIT (tyrosine kinase receptor)

Adenocarcinoma of SI
~ most in duodenum including ampulla of Vater
~ most metastasized to LV by the time of diagnosis

Carcinoid Tumours
~ cells making bioactive compounds causing overactive production of hormones
~ usually seen in older people
~ can cause a clinical syndrome
~ appendix is m/c site of gut
~ rarely metastasize, yellow tan in appearance

Gastrointestinal Lymphoma
~ MALT and H. pylori (chronic gastritis)  increase T and B cells  polyclonal B cell
hyperplasia  monoclonal B cell neoplasm
~ secondary involvement by systemic dissemination of non-Hodgkin lymphoma
~ gut is the most common extranodal location

Acute Appendicitis
~ obstruction with fecalith
~ mucinous fluid  increase pressure  collapse veins  ischemia  exudation

Tumours of the Appendix

~ carcinoids: m/c form of neoplasia in appendix
~ 1) mucocele – dilation of appendix lumen, fecalith accumulation
~ 2) mucinous neoplasms – benign mucinous cystademoa to mucinous
cystadenocarcinoma (invades wall, and can lead to intraperitoneal cancer =
pseudomyxoma peritonei)
~ 3) cystadenoma – like tumours in ovary, cystadenocarcinomas invade wall, tumor goes
into peritoneal cavity and is filled with mucin (pseudomyxoma peritonei)

Hepatic Injury:
~ 5 responses: inflammation  degeneration  cell death  fibrosis  cirrhosis
~ degeneration can be ballooning or foamy
~ can remove 75% of the liver and get minimal hepatic impairment and within a few
weeks, the LV mass can regenerate itself

Jaundice and Cholestasis

~ 2 reasons for bile:
~ 1) bile is an elimination pathway for ex cholesterol
~ 2) bile promotes emulsification of fats
~ Jaundice: yellos skin and sclerae
~ Cholestasis: retention of bilirubin and other solutes

Bilirubin and Bile Acids

~ bilirubin = end product of heme degradation
~ usually from breakdown of erythrocytes, and premature destruction of newly formed
erythrocytes in bone marrow
~ heme  biliverdin  bilirubin (by biliverdin reductase)
~ bilirubin glucuronides  colorless urobilinogens (by bacterial beta-glucuronidases)
and excreted in feces
~ bile acids – steroid molecules
~ primary human bile acids – cholic acid and chenodeoxycholic acid
~ almost all conjugated and deconjugated bile acids are reabsorbed (esp ileum) and
returned to liver for uptake, reconjugation, and resecretion
~ fecal loss of bile acids is remade
Pathophysiology of Jaundice
~ accumulation of unconjugated bilirubin and bilirubin glucuronides in the liver
~ icterus = yellowing of sclerae
~ 2 differences between two forms of bilirubin:
~ 1) unconjugated bilirubin is tightly bound to serum albumin and is insoluble in water at
physiological pH
~ kernicterus = accumulation of unconjugated bilirubin in brain
~ 2) conjugated biliruin is water soluble and excess is excreted in urine
~ jaundice occurs when one or more of these happens:
~ xs production of bilirubin
~ reduced hepatic uptake
~ impaired conjugation
~ decreased hepatocellular excretion
~ impaired bile flow
~ m/c causes of jaundice:
~ hemolytic anemias, hepatitis, and obstruction to flow of bile
~ most newborns have neonatal jaundice
~ breast-fed may be more jaundiced because of beta-glucuronidase in maternal milk

Cholestasis
~ can also present as jaundice
~ pruritus – symptom related to increased plasma bile acids
~ skin xhanthomas – local cholesterol accumulation
~ usually see elevated level of serum alkaline phosphatase
~ reduced bile flow can also be related to intestinal malabsorption
~ if it’s extrahepatic biliary obstruction it can be surgically fixed
~ if intrahepatic or hepatocellular secretory failure = intrahepatic cholestasis  can’t be
fixed by surgery

Hepatic Failure
~ most sever clinical consequence of liver disease
~ 3 categories:
~ 1) massive hepatic necrosis
~ 2) chronic liver disease
~ 3) hepatic dysfunction without overt necrosis

Cirrhosis
~ usually alcohol abuse, and chronic hepatitis, biliary disease, and iron overload
~ end stage chronic liver disease:
~ 1) bridging fibrous septa
~ 2) parenchymal nodules
~ 3) disrupt architecture of entire liver
~ diffuse fibrosis
~ 3 major pathologic mechanisms:
~ 1) hepatocellular death
 ~ 2) regeneration
~ 3) progressive fibrosis
~ get extra collagen in cirrhosis from perisinusoidal stellate cells (store fat and Vit A)
~ these get activated and transform into myofibroblast-like cells
~ excess collagen synthesis and deposition d/t:
~ 1) chronic inflammation
~ 2) cytokine production
~ 3) disruption of extracellular matrix
~ 4) stimulation of stellate cells by toxins

Portal HTN
~ increase resistance to portal blood flow
~ prehepatic, posthepatic, and intrahepatic causes
~ dominant intrahepatic cause – cirrhosis

Ascites
~ xs fluid in peritoneal cavity
~ pathogenesis involves:
~ 1) sinusoidal HTN
~ 2) hepatic lymph  peritoneal cavity
~ 3) renal retention of sodium and water b/c of secondary hyperaldosteronism

Portosystemic Shunts
~ increased portal pressure and bypasses systemic and portal circulation beds
~ common sites: rectum, cardio-esophageal junction, retroperitoneum, falciform ligament
of liver
~ caput medusae – dilated subcutaneous veins extending from umbilicus towards ribs

Splenomegaly
~ long-standing congestion
~ not necessarily correlated with other features of portal hypertension

Inflammatory Disorders
~ liver is involved with all bloodborne infections
~ primary hepatic infections – viral
~ 1) EBV – infectious mononucleosis
~ 2) cytomegalovirus or herpes virus - immunocompromised
~ 3) yellow fever – tropical
~ but viral usually refers to hepatitis viruses