Recommendations for a step-wise comparative approach to the evaluation of new screening tests for colorectal cancer.

Background: New screening tests for colorectal cancer continue to emerge, but the evidence needed to justify their adoption in screening programs remains uncertain.

Methods: A review of the literature and a consensus approach by experts was undertaken to provide practical guidance on how to compare new screening tests with proven screening tests.

Results: Findings and recommendations from the review included the following: Adoption of a new screening test requires evidence of effectiveness relative to a proven comparator test.

Changing epidemiology of colorectal cancer makes screening sigmoidoscopy less useful for identifying carriers of colorectal neoplasms.

Background: There is renewed interest in flexible sigmoidoscopy (FS) colorectal cancer (CRC) screening following trials showing significantly reduced CRC incidence and mortality.

Aims: To evaluate the potential usefulness of FS screening in our population.

Methods: We examined rectosigmoid (RS) cancer epidemiology in our Jewish population using Israel National Cancer Registry data, computed by CRC site, age groups, and gender.

Can a gastrointestinal pathologist identify microsatellite instability in colorectal cancer with reproducibility and a high degree of specificity?

Clinical features usually initiate evaluation for Lynch Syndrome (LS) but some colorectal cancer (CRC) histopathology findings are compatible with high microsatellite instability (MSI-H) that also occurs in LS. This led to the suggestion that pathologists request MSI analysis, which is an expensive addition to routine histology. We aimed to see if a Gastrointestinal Pathologist could identify MSI-H features with reproducibility and high (95%) specificity (MSI-H 95%).

Follow-up of patients undergoing both semiquantitated immunochemical fecal occult blood and colonoscopy examinations.

The semiquantitated immunochemical fecal occult blood test (I-FOBT) used for colorectal cancer (CRC) screening has had its long-term performance characteristics determined by clinical follow-up or sometimes by colonoscopy as the 'gold standard'. We reanalyzed a file of total colonoscopy patients who also prepared three I-FOBTs, processed by the OC-MICRO instrument, using at least 50 ng Hb/ml buffer threshold to determine a positive test. The performance of both tests was evaluated by the National Cancer Registry follow-up to identify new CRCs and by determining the effects of the number of tests prepared and their thresholds for analysis, sex, and age on results.

Risk for colorectal cancer in elderly persons and possible methodologies for their screening.

Objectives: Most colorectal cancer (CRC) screening guidelines recommend average-risk screening up to the age of 75 years. However, increasing life span and incidence of proximal CRC could require changes to the age guidelines and adapting screening methodology for the elderly persons. Therefore, we reviewed our CRC epidemiology, international screening age-guidelines, and screening tests for the elderly persons and presented our long-term results of colonoscopy and semi-quantitated immunochemical fecal occult blood tests (I-FOBTs) in individuals that are 75 years or more.

A protocol for genetic evaluation of patients with multiple colorectal adenomas and without evidence of APC gene mutation.

Background: Patients with multiple (< 100) colorectal adenomatous polyps are at increased risk for colorectal cancer. Genetic evaluation of those patients who test negative forAPCgene mutation is both a clinical and economic burden but is critical for counseling and surveillance. In Israel, this is confounded by the fact that national health insurance does not fully cover genetic evaluation of APC gene exon 16.

The changing epidemiology of colorectal cancer and its relevance for adapting screening guidelines and methods.

In many countries at risk for colorectal cancer (CRC), screening guidelines provide average-risk screening for patients aged between the ages of 50 and 75 years. However, an earlier onset of CRC, an increasing life span and an incidence of right-sided CRC have been noted, which could require changes in age guidelines and screening methodology, especially for the elderly. We examined this in our Jewish populations using Israel Cancer Registry data, 1980-2008, computed by age groups, sex, ethnic groups, cancer site, and cancer stage.

Cumulative evaluation of a quantitative immunochemical fecal occult blood test to determine its optimal clinical use.

Background: Quantified, human hemoglobin (Hb)-specific, immunochemical fecal occult blood test (IFOBT) measurements are now used for colorectal cancer (CRC) screening. The objective was to evaluate sensitivity and specificity for CRC and advanced adenomatous polyps (APs) by the fecal Hb threshold used to determine a positive test and the number of IFOBTs prepared per test, so as to determine the least number of colonoscopies required to detect a neoplasm.

Methods: Cumulative data were analyzed from a prospective cross-sectional double-blind study of 1682 consecutive, ambulatory, nonbleeding colonoscopy patients who volunteered for IFOBTs, most of above average risk, from 3 ambulatory-endoscopy centers.

Pancreatic cancer in Israel: the epidemiology, possibilities of prevention, early detection and screening.

Pancreatic cancer is not a common malignancy in Israel, but it is the third most common cause of cancer mortality, attributable to a lack of screening tests, inaccessibility of the pancreas, and late cancer stage at diagnosis. We reviewed the epidemiology, known risk factors and screening methods available in Israel and describe the Israeli national consortium that was established to identify persons at risk and decide on screening methods to detect and treat their early-stage pancreatic cancer. In collaboration with the Israel National Cancer Registry, we evaluated the incidence and trends of the disease in the Jewish and non-Jewish populations.

Familial adenomatous polyposis.

Familial adenomatous polyposis (FAP) is characterized by the development of many tens to thousands of adenomas in the rectum and colon during the second decade of life. FAP has an incidence at birth of about 1/8,300, it manifests equally in both sexes, and accounts for less than 1% of colorectal cancer (CRC) cases. In the European Union, prevalence has been estimated at 1/11,300-37,600.

Sensitivity, but not specificity, of a quantitative immunochemical fecal occult blood test for neoplasia is slightly increased by the use of low-dose aspirin, NSAIDs, and anticoagulants.

Objectives: We evaluated the effect of the use of aspirin, nonsteroidal anti-inflammatory drugs (NSAIDS), and anticoagulants on the performance of immunochemical fecal occult blood test (I-FOBT).

Methods: A prospective, cross-sectional study of 1,221 ambulatory patients having total colonoscopy after preparing three I-FOBTs. Information regarding the use of medications was collected from the health medical organization (HMO) database.

The changing epidemiology of upper gastrointestinal cancers in Israel: clinical and screening implications.

Western countries and now developing countries have noted a decreasing incidence of upper gastrointestinal (UGI) (esophageal and gastric) cancers, but increasing distal esophageal adenocarcinoma and a shift to fundal-sited gastric cancer. We examined these trends in Israeli Jewish and non-Jewish populations, drawing conclusions on the need to promote prevention and/or screening. Israel Cancer Registry UGI cancer data were computed by ethnicity, immigration after 1990, sex, sites and histology, examining age-standardized rates (ASR)/10 for 2000-2005 and incidence trends during 1980-2005.

A familial gastrointestinal cancer clinic: organization, aims and activities, 2004-2007.

Background: Dedicated, organ-specific screening clinics have been shown to significantly reduce cancer morbidity and mortality.

Objectives: To establish a dedicated clinic for Clalit Health Service patients at high risk for hereditary gastrointestinal cancer and to provide them with clinical and genetic counseling, diagnostic screening and follow-up.

Results: During the 3 years of the clinic's activity, 634 high risk families, including 3804 at-risk relatives, were evaluated.

A quantitative immunochemical fecal occult blood test for colorectal neoplasia.

Background: Guaiac-based fecal occult blood tests (FOBTs) for colorectal cancer screening are not specific for human hemoglobin and have low sensitivity. Automated-development, immunochemical FOBT is quality-controlled, is specific for human hemoglobin, and does not require diet restriction.

Objectives: To measure the sensitivity and specificity of quantitative immunochemical fecal hemoglobin measurements for detection of cancer and advanced adenoma in patients undergoing colonoscopy, to determine fecal hemoglobin thresholds that give the highest posttest probability for neoplasia, and to determine the number of immunochemical FOBTs needed.

Changing sites of colorectal cancer in the Israeli Jewish ethnic populations and its clinical implications.

Countries at risk for colorectal cancer noted an increase in right-sided colorectal cancer. We examined this in the Israeli Jewish populations. Israel Cancer Registry data, 1982-2001, were computed by sex, age, ethnic group and colorectal cancer site: 'rectal cancer' included the recto-sigmoid junction, 'right-sided' colorectal cancer included proximal colon up to and including the splenic flexure.

The changing incidence and sites of colorectal cancer in the Israeli Arab population and their clinical implications.

Israeli Arabs have been at low risk for colorectal cancer (CRC) and had mainly proximal cancer, but increasing CRC is now noted. We examined this trend and CRC site and compared them to the total Jewish population and to the low-risk Jews of Asian-African origin. Israel Cancer Registry CRC data, 1982-2002, for Arabs and Jews was computed by gender, age and site: rectal cancer included recto-sigmoid junction; "right-sided" CRC included the proximal colon up to and also the splenic flexure.

Familial adenomatous polyposis: The practical applications of clinical and molecular screening.

Familial adenomatous polyposis (FAP) is an autosomal dominant condition mostly due to a mutation of the APC gene on the chromosome 5q. Carriers have an almost 100% chance of developing colorectal cancer after having multiple (typically 100s to 1000s) of adenomatous polyps. It is usually readily identified through this phenotype of multiple adenomas.

Germ line mutations of mismatch repair genes in hereditary nonpolyposis colorectal cancer patients with small bowel cancer: International Society for Gastrointestinal Hereditary Tumours Collaborative Study.

Purpose: The aim of study was to determine the clinical characteristics and mutational profiles of the mismatch repair genes in hereditary nonpolyposis colorectal cancer (HNPCC) patients with small bowel cancer (SBC).

Experimental Design: A questionnaire was mailed to 55 members of the International Society for Gastrointestinal Hereditary Tumours, requesting information regarding patients with HNPCC-associated SBC and germ line mismatch repair gene mutations.

Results: The study population consisted of 85 HNPCC patients with identified mismatch repair gene mutations and SBCs.

Evaluation of a desk top instrument for the automated development and immunochemical quantification of fecal occult blood.

Background: The guaiac fecal occult blood test (FOBT) for colorectal cancer (CRC) screening is user dependent and not specific for human hemoglobin (Hb). The automated-developed, quantitative, immunochemical human Hb FOBT (I-FOBT) is specific, allows for quality control and selection of a suitable Hb level, with optimal sensitivity and specificity, for colonoscopy.

Material/methods: We evaluated a desktop instrument, OC-MICRO (Eiken, Japan), which automatically develops and quantifies 50 fecal tests/hr for Hb; for ease of use, test reproducibility and stability and intra-patient daily I-FOBT variation; clinical evaluation included sensitivity and specificity for neoplasia in patients undergoing colonoscopy.

Performance characteristics and evaluation of an automated-developed and quantitative, immunochemical, fecal occult blood screening test.

Objectives: Guaiac fecal occult blood colorectal cancer (CRC) screening tests (FOBT) are faulted for low sensitivity and nonspecificity for human hemoglobin (Hb). Automated-developed, immunochemical, human Hb FOBT (I-FOBT) is specific, eliminates diet restrictions, and Hb quantification allows selection of a threshold for colonoscopy. Aims were to determine 1) test reproducibility; 2) test stability; 3) intrapatient daily I-FOBT variation; 4) test sensitivity and specificity for neoplasia in 500 symptomatic/high-risk patients undergoing colonoscopy; and 5) to correlate fecal Hb measurements with findings.

Characteristics of familial juvenile polyps expressing cyclooxygenase-2.

Objectives: Familial juvenile polyposis (FJP) is a dominant genetic disorder characterized by colorectal, gastric, and small bowel juvenile polyps, and high risk for gastrointestinal cancer. Patients are treated by repeated endoscopic polypectomies and elective surgery. We determined the characteristics of FJP polyps expressing cyclooxygenase-2 (COX-2).

Cyclooxygenase-2 expression in the hereditary mixed polyposis syndrome.

Hereditary mixed polyposis syndrome (HMPS), characterized by hyperplastic, juvenile, admixed, serrated adenomas and eventually colorectal cancer, is managed by repeated polypectomy and surgery. We determined if HMPS polyps express cyclooxygenase-2 (COX-2). Nineteen recent HMPS polyps, from five family members, were stained for COX-2.

Trends in colorectal cancer incidence and mortality in the Israeli Jewish ethnic populations.

Background: Ashkenazi Jews, as compared to non-European Jews and non-Jews, are at increased risk for colorectal cancer (CRC), this is attributed to genetic susceptibility and/or lifestyle.

Aims: To follow Israeli long-term trends in CRC incidence and mortality and their associations with ethnicity.

Methods: All Israeli CRC data accumulated 1970-2001 was used, age standardized rates (adjusted to world standard population) was computed by cancer site, US Surveillance, Epidemiology and End Results Program (SEER) Stage and ethnic group (continent of birth: Europe-America, Asia, Africa, Israel).