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ADENOCARCINOMA • mutation of APC (adenomatous polyposis gene). The protein encoded by APC is important in activation of oncogene c-myc and cyclin D1, which drives the progression to malignant phenotype. • abnormal DNA methylation can cause silencing of tumor suppressor genes or activation of oncogenes, compromising the genetic balance and ultimately leading to malignant transformation. • Other important genes KRAS oncogene , chromosome 18 loss of heterozygosity (LOH) leading to inactivation of SMAD4 (DPC4), and DCC (deleted in colon cancer) tumor suppression genes. Chromosome arm 17p deletion and mutations affecting p53 tumor suppressor gene confer resistance to programmed cell death (apoptosis) and are thought to be late events in colon carcinogenesis. ADENOCARCINOMA •Hematochezia or blood-streaked stool •Change in bowel habits (severe constipation due to obstruction) •Abdominal discomfort or pain due to mass •Narrow stools •Feeling of unfinished bowel movement •Weight loss due to cachexia • Annular lesions – irregular, circumferential masses that severely constrict the bowel lumen – margins of the carcinoma show overhanging edges, the tumor shelf or shoulder (termed "APPLE-CORE or NAPKIN RING" lesion). – mucosal folds in the narrowed segment are destroyed; ulceration may be present LATERAL VIEW: Prominent Apple Core Deformity and Irregular Mucosa DIFFERENTIAL DIAGNOSIS: INFLAMMATORY BOWEL DISEASE • an idiopathic disease, probably involving an immune reaction of the body to its own intestinal tract. • The 2 major types of IBD are ulcerative colitis and crohn’s disease INFLAMMATORY BOWEL DISEASE • The pathophysiology is under active investigation. • The common end pathway is inflammation of the mucosal lining of the intestinal tract, causing ulceration, edema, bleeding, and fluid and electrolyte loss. • Possible factors related to this event include: 1. pathogenic organism (as yet unidentified) 2. immune response to an intraluminal antigen 3. an autoimmune process ULCERATIVE COLITIS Clinical Manifestations: Blood streaked stool Abdominal pain or cramps Urgency and tenesmus Weight loss in severe cases Extracolonic manifestations Radiologic Findings – Continuous lesion – lead pipe appearance of the colon because of the loss of normal haustral markings. – granular mucosal pattern CROHN’S DISEASE • involve any segment of the gastrointestinal tract from the mouth to the anus. Manifestations include the ff: • Diarrhea due to malabsoprtion, and abdominal pain • Fever due to infection • fatigability due to anemia • weight loss • blood streaked stool in colonic involvement • May also present with intestinal obstruction ie borborygmi, abdominal distention • bloating, crampy pain CROHN’S DISEASE • discontinuous (skip) lesions • Aphthae appear as 1 to 2 mm barium-filled craters surrounded by a lucent halo enlarge, they coalesce forming a lattice work of confluent ulcers resulting in the so called "COBBLESTONE" appearance COLON DIVERTICULITIS • inflammation of one or more diverticula • pathogenesis : -Fecal material/undigested food particles may collect in a diverticulum obstruction distension of the diverticula Vascular compromise microperforation /macroperforation then ensue. COLON DIVERTICULITIS Clinical Manifestations: Abdominal pain, hematochezia Fever, leukocytosis, nausea, vomiting, flatulence, palpable masses, muscle guarding, and partial obstruction constipation, diarrhea, and bloating • Soft-tissue densities suggestive of abscesses • Narrowing, deformity, or displacement of the bowel lumen