GIT 4th 2015 CRC.

Colorectal neoplasia:

Dr.Mohamed AlshekhaniProfessor in Medicine

MBChB-CABM-FRCP-EBGH2015

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CRC: Epidemiology

• Incidence higher for men (F/M 1.4:1), with considerable geographic variation; the majority (60%) from developed regions.

• Blacks have higher incidence & mortality.

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Predisposing factors: IBD

• Increased risk depending on:

• Duration of IBD; progressively increases after 10 years (2%), 20 years (8%)& 30 years (18%).

• The extent & location: Pancolitis& distal colitis confer high& intermediate colorectal cancer risks, respectively,proctitis has minimal (if any) increased risk.

• A concomitant diagnosis of primary sclerosing cholangitis& family history of CRC (especially <50 years).

• Age of onset of disease: not important.

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Predisposing factors: T2DM

• 30% higher risk due to higher concentrations of circulating insulin and/or insulin-like growth factors related to obesity.

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Predisposing factors: Ureterosigmoidostomy

• Associated with a markedly elevated risk (100-500 times higher than general population), with a prolonged latency period that can exceed 50 years.

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Predisposing factors:Cholecystectomy

• Associated with modesty increased risk, BZ of altered fecal bile acid composition.

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Predisposing factors : Non-syndromic Family History

• Influenced by:

• The degree of relationship

• Number of relatives affected

• Age at diagnosis of family member.

• First-degree relative or two second-degree relatives at any age: lifetime risk is elevated *2-3.

• When 2 first-degree relatives are affected, increased by *3-4.

• Diagnosis of CRC in a first-degree relative at age 50 years or younger increase risk by *3-4.

• A family history of CR adenoma appears to confer similarly increased CRC risks.

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Predisposing factors : Hereditary Colorectal Cancer Syndromes

• 1. Hereditary Nonpolyposis Colorectal Cancer:

• The most common type of hereditary CRC (2-3% of all cases).

• Autosomal dominant.

• Colorectal adenomas develop at a relatively young age ( 20- 30 years) &progress to CRC more quickly than sporadic adenomas. Lifetime risk is 80%, with a mean age at diagnosis of 44 ys.

• Clinicopathologic features include proximal colon location (up to 2/3), poorly differentiated histology& MSI high phenotype.

• Endometrial AC is the 2ND most common ca in HNPCC,30-60%.

• Additional HNPCC-related malignancies are gastric, biliary tract, urinary tract, ovarian &small-bowel cancer.

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Predisposing factors : 2.Familial Adenomatous Polyposis

• Incidence is 1/6000-13,000 live birdis, <1% of CRC.

• Germline mutations in APC gene,Autosomal dominant.

• Characterized by hundreds-thousands of adenomatous polyps distributed throughout the colorectum.

• Mean age at polyp diagnosis of 16 years.

• Without intervention, nearly all patients will develop colorectal cancer, with a mean age at cancer diagnosis of 39 years.

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Predisposing factors : 2.Familial Adenomatous Polyposis

• Duodenal adenomas, particularly in the periampullary region, found in 50-90% & a lifetime risk for duodenal cancer of 4- 12%.

• Other malignancies: papillary thyroid cancer, childhood hepatoblastoma, gastric adenocarcinoma.

• Benign: gastric fundic gland polyps, small-bowel adenomas, osteomas, desmoid tumors, supernumerary teeth, congenital hypertrophy of the retinal pigment epithelium.

• APC mutational analysis can be used to confirm the diagnosis.

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Predisposing factors : 3.Attenuated FAP

• AFAP is a subset of FAP.

• Affected individuals develop fewer (<100), often more proximally distributed, colorectal adenomas.

• Clinical presentation may be delayed until 4th or 5th decade of life.

• The cumulative CRC risk appears to be slightly lower for AFAP (70%) than for classic FAP (100%).

• Extracolonic features include UGIT polyps but less prominent than in classic FAP.

• Germline mutations are typically found in the extreme distal or proximal ends of the APC gene.

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Predisposing factors : 4.MTH-Associated Polyposis

• Characterized by heterozygous & homozygous mutations in MTH gene (involved in DNA base-excision repair).

• These mutations may be found in 1% (heterozygous) & 0.5- 1% (homozygous) of general population.

• It is autosomal recessive, with biallelic MTH mutations predisposing to somatic alterations in APC and/or other key growth-regulating genes.

• The clinical spectrum of MAP often resembles AFAP.

• Genetic testing for MTH mutations is not yet routinely performed.

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Predisposing factors : 5.Peutz-Jeghcrs Syndrome

• The estimated incidence is 1/8300- 280,000 live birdis.

• Mutations in STK11/LKBI gene inherited with AD pattern.

• Clinical manifestations consist of mucocutaneous melanocytic macules (particularly in perioral region& over buccal mucosa) & GIT hamartomatous polyps, which may present during adolescence or early adulthood with symptoms of abdominal pain, bleeding,obstruction, or intussusception.

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• PJS-associated hamartomatous polyps are most commonly located in SI (60- 90%) but in the colorectum, biliary tract, resp tract, or GIT.

• Colorectal adenomas can also be observed.

• Cancer risk markedly increased, with 50-90% of affected individuals developing at least one malignancy over life time: colorectal cancer, 40%; gastric, 30- 60%; pancreas, 35%; small intestine, 15- 30%; esophagus, 0.5-33%; breast, 54%; ovary, 21%;lung, 15%; cervix, 10%; uterus, 9%; testes, 9%.

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• Proposed diagnostic criteria require a combination of:

• Histologically confirmed hamartomatous polyp(s) with distinctive PJS features (arborizing smooth muscle fibers)

• Mucocutaneous melanocytic macules

• &/or a Known family history of PJS.

• STK11/LKB1 mutational analysis can also be performed to confirm a suspected PJS diagnosis.

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Predisposing factors : 7.Juvenile Polyposis Syndrome

• The incidence is 1/16,000 -100,000 live births.

• Mutations in BMPRIA, SMAD4,PTEN genes.

• Benign juvenile hamartomatous polyps are relatively common, occurring as solitary, sporadic lesions in up to 2% of children <10 ys.

• In contrast, patients with JPS have multiple polyps that are distributed throughout the GIT.

• Abdominal pain, diarrhea, bleeding, obstruction, or intussusception may occur during childhood or adolescence, with an average age at JPS diagnosis of 18.5 years.

• 2/3 of untreated patients with JPS develop CRC at 60 years.

• Other Cans: gastric, duodenal,pancreatic cancer.

• Some may also have hereditary hemorrhagic telangiectasia, which can present with digital clubbing.

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Predisposing factors : Juvenile Polyposis Syndrome

• Clinical diagnosis of JPS can be made based on any of:

• (1) Three or more juvenile polyps in the colorectum

• (2) Multiple juvenile polyps throughout the GIT, or 3 or any number of juvenile polyps coupled with a family history of JPS.

• Genetic testing is not yet routinely performed in clinical practice.

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Predisposing factors : 8.Hyperplastic Polyposis

• A familial predisposition to multiple and/or large hyperplastic polyps in the colorectum.

• CRC risk is increased to an unknown degree.

• Diagnosis made if any of the following criteria are met:

• (1) 5 or more histologically confirmed hyperplastic polyps located proximal to the sigmoid colon, of which two or more are larger than 1 cm in diameter.

• (2) Any number of hyperplastic polyps located proximal to the sigmoid colon in a person who has one or more first-degree relatives with documented HPP.

• (3) >30 hyperplastic polyps distributed throughout the colorectum.

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CRC Screening: Average Risk

• ¾ of all CRCs are diagnosed in average-risk persons (persons without previously identified CRC risk factors).

• 90% occur during the sixth decade of life or later.

• Clinicians should perform an individualized assessment of risk for CRC in all adults.

• Those with average risk should begin screening at age 50 years (age 40 years for black or DCs)& continue at intervals based on the method of screening chosen &the results of screening until age 75 years or until there is a life expectancy of <10 years.

• Multiple test options are used.

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• The tests include:

• (1) tests that detect premalignant adenomas & CRC

• (flexible sigmoidoscopy,colonoscopy, double-contrast barium enema, CT colonography)

• (2) tests that primarily detect colorectal cancer (stool assays).

• Existing data are insufficient to support CT colonography or stool DNA testing for average-risk CRC screening.

• The ACP guidance statement recommends using a stool-based test, flexible sigmoidoscopy,or optical colonoscopy for screening in patients at average risk.

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• 1.Guaiac Fecal Occult Blood Test:

• Uses a reagent that changes color in presence of peroxidase, which is found in human blood, animal blood& other dietary sources.

• Requires collection of two samples from three consecutive stools (six samples total).

• Samples can be obtained at home & mailed in to a clinical laboratory for processing & analysis.

• Results in statistically significant reductions in CRC incidence 17-20% & mortality 15-33% with regular screening.

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• Limitations of gFOBT screening are:

• Low sensitivity for advanced adenomas (11- 41%)

• Diet & medication interactions that may produce false-positive or false-negative results.

• The need for annual testing if negative

• The need for appropriate diagnostic follow-up (ideally by colonoscopy) if testing is positive to achieve maximum benefit.

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• 2.Fecal Immunochemical Test:

• Incorporate antibodies directed against the human globin protein, improving its specificity over gFOBT.

• FIT sensitivity 60- 85% for CRC&25-50% for advanced adenomas.

• Sample collection can be completed at home& pretest dietary restrictions arc not necessary.

• As with gFOBT screening, FIT screening requires annual testing for negative results & appropriate diagnostic follow-up for a positive result.

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• 3.Stool DNA Test:

• Stool DNA (sDNA) assays tar get molecular alterations that originate directly from lesion of interest.

• Currendy, an entire stool specimen (30 g minimum) must be submitted for evaluation.

• It demonstrated moderate sensitivity for CRC (25-58%) & lower sensitivity for adenomas 1 cm or larger (8-45%).

• At present, sDNA testing is not routinely available for colorectal cancer screening.

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• 4.Flexible Sigmoidoscopy

• Endoscopic evaluation of the lower colorectum (up to 60 cm).

• Performed after limited bowel preparation (two enemas) without conscious sedation.

• Adenomas of any size or polyps larger than 5 mm should undergo full colonoscopy.

• Reduces mortality by 60%.

• Proximal neoplasia is more common in blacks & older women, proceeding directly to colonoscopy for screening may be more prudent in these patients.

• A potential complication is bowel perforation, which occurs in<1/ 20,000.

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• 5.CT Colonography

• Evaluates entire colorectum,&limited extracolonic structures in the abdomen &pelvis.

• Dietary restrictions, full cathartic preparation, oral contrast ingestion, air insufflation are required.

• It has estimated sensitivities of > 90% for CRC & 85-93% for polyps 1 cm or larger.

• Diagnostic and/or therapeutic colonoscopy is recommended for one or more polyps 1 cm or larger, or three or more polyps 6 mm or larger.

• Bowel perforation can occur from CT colonography, but extremely low (<1/10,000).

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• 6.Colonoscopy:

• Evaluates entire colorectum.

• Dietary restrictions , full cathartic preparation are required prior to the procedure&conscious sedation is needed.

• Therapeutic polypectomy can be completed during the baseline procedure.

• Results in substantial reductions in CRC incidence (53- 72%) & mortality (31%).

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• If no polyps are detected during a high-quality baseline colonoscopy (cecal intubation accomplished, mucosa well visualized with minimal fecal debris,withdrawal time >6 minutes), the next colonoscopy can be performed in 10 years.

• Miss rates:5% for CRC, 2-12% for polyps 1 cm or larger, >20% for polyps 6 mm or larger.

• Risks: significant bleeding (2-6/1000) bowel perforation (1/1000).

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Surveillance: Postpolypectomy

• Patients with one or > adenomas detected during CRC screening are at increased risk for developing subsequent advanced CR neoplasia.

• The strongest predictors of future risk depends on:

• Multiplicity

• Size

• Morphology

• histology.

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• Low-risk patients (1-2 adenomas,<1 cm, tubular morphology & low-grade dysplasia), surveillance colonoscopy repeated in 5-10 ys.

• High-risk patients (>3 adenomas, >1 cm, villous morphology, or high-grade dysplasia), surveillance colonoscopy repeated in 3 years, assuming complete removal of the index lesion(s).

• If >10 adenomas are detected during a single evaluation, the next colonoscopy should be repeated in < 3 years &possibility of an underlying hereditary cancer syndrome should be considered.

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• Patients with large, sessile adenomas removed piecemeal should undergo repeat colonoscopy at a relatively short interval (2-6 mondis) to ensure complete resection.

• Patients with small, hyperplastic,rectal polyps only (not meeting criteria for hyperplastic polyposis syndrome) should undergo surveillance according to average-risk screening guidelines.

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Surveillance: Post CRC treatment

• Patients with CRC who receive potentially curative treatment (such as surgery, chemotherapy, radiation therapy, or a combination of these) should be monitored aggressively to detect early recurrence & perform surveillance for metachronous CR neoplasia( in the remaining colorectal segment).

• Preoperative clearing colonoscopy (or CT colonography for obstructing tumors) is recommended to identify synchronous malignancies, which occur in 2-7% of all patients with CRC.

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Surveillance: Post CRC treatment

• Following treatment,surveillance colonoscopy should be repeated 1 year after the clearing examination.

• If normal findings are observed, subsequent surveillance colonoscopies can be performed at 3 years& 5 years after the clearing examination, respectively. If adenomas are detected, surveillance intervals can be tailored according to postpolypectomyguidelines.

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CRC: Clinical presentations

• Symptoms are often related to anatomic location& tumor size.

• For tumors originating in the Proximal colon (cecum to splenic flexure): common symptoms include nonspecific abdominal pain, unintentional weight loss& occult GIB.

• Tumors in distal colon (descending & sigmoid) or rectum: can present with increased stool frequency (small caliber), incomplete evacuation, constipation, or hematochezia.

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CRC: Clinical presentations

• Clinical signs that may be related to CRC are anemia, fistula, mass lesion, or unexplained abscess.

• At presentation, 40% have localized disease, 36% have regional metastases, 19% have distant metastases& 5% are unstaged.

• Relatively frequent sites for distant metastases are the liver, peritoneal cavity, lungs; adrenal glands, ovaries, and skeletal system are less commonly involved.

• Metastases to the brain or central nervous system are rare.

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CRC: Diagnosis & Staging

• Colonoscopy is the initial test of choice for evaluating symptoms suggestive of CRC because biopsies can be obtained.

• Staging is determined by depth of tumor invasion, extent of nodal involvement,&presence or absence of distant metastases.

• For CRC, the clinical (or preoperative) stage is generally based on physical exam, abdomino-pelvic CT & chest radiography findings.

• The rectal cancer staging usually includes EUS or pelvic MRI in addition to the tests for colon cancers.

• The final pathologic stage is determined following surgery.

• The 5-year relative survival rate is 65%, with estimates of 90%, 70%, & 12% for localized, regional& distant stages of disease, respectively.

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BO5 1:

• Most of the CRCs occur in:

• Average risk persons.

• Those with HNPCC.

• FAB.

• AFAP.

• PJS.

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BO5 2:

• The highest risk for developing CRC is among:

• Post cholecystectomy patients.

• Post ureterosigmoidostmy patients.

• FAB.

• AFAP.

• PJS.

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BO5 3:

• All are reasons not to do cholecystectomy in asymptomatic gall stones, except:

• Associated morbidity.

• Associated mortality.

• Risk of CRC.

• Weight gain.

• Missing other diagnoses.

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BO5 4:

• The 2nd most common cancer in FAB after CRC is:

• Fundal gastric caner.

• Periampullary cancer.

• Ovarian cancer.

• Breast cancer.

• Uninary bladder cancer.

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BO5 5 :

• The ideal method for CRC screening is:

• Sigmoidoscopy.

• Fecal occult blood test.

• CT colonogarphy.

• Colonoscopy.

• Barium enema.

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BO5 6 :

• Screening for CRC in average risk persons should start earlier than 50 years in:

• Women.

• Men.

• Black.

• All.

• None.

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BO5 7 :

• All are risk for CRC except:

• FAP.

• AFAP.

• PJS.

• Family history of colorectal adneoma.

• Family history of CRC.

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BO5 8 :

• The following are advised to prevent CRC in average risk persons:

• Increase fruit intake.

• Increase vegetables.

• Avoid smoking.

• NSAIDs use.

• Physical activity.

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BO5 9 :

• FAP & AFAP differ from each other in all of these features except:

• Number of polyps.

• Risk of CRC.

• Age at diagnosis of CRC.

• Mutant gene.

• Extra colonic features.

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BO5 10 :

• The strongest predictors of future CRC risk depends on all the following except:

• Multiplicity.

• Size.

• Morphology.

• Histology.

• None of the above.

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Thanks for attention

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GIT 4th 2015 CRC.

Health & Medicine

Transcript of GIT 4th 2015 CRC.