Data From a One-Stop-Shop Comprehensive Cancer Screening Center.

PURPOSE: Cancer is the second leading cause of death globally. However, by implementing evidence-based prevention strategies, 30%-50% of cancers can be detected early with improved outcomes. At the integrated cancer prevention center (ICPC), we aimed to increase early detection by screening for multiple cancers during one visit. METHODS: Self-referred asymptomatic individuals, age 20-80 years, were included prospectively. Clinical, laboratory, and epidemiological data were obtained by multiple specialists, and further testing was obtained based on symptoms, family history, individual risk factors, and abnormalities identified during the visit. Follow-up recommendations and diagnoses were given as appropriate. RESULTS: Between January 1, 2006, and December 31, 2019, 8,618 men and 8,486 women, average age 47.11 ± 11.71 years, were screened. Of 259 cancers detected through the ICPC, 49 (19.8%) were stage 0, 113 (45.6%) stage I, 30 (12.1%) stage II, 25 (10.1%) stage III, and 31(12.5%) stage IV. Seventeen cancers were missed, six of which were within the scope of the ICPC. Compared with the Israeli registry, at the ICPC, less cancers were diagnosed at a metastatic stage for breast (none v 3.7%), lung (6.7% v 11.4%), colon (20.0% v 46.2%), prostate (5.6% v 10.5%), and cervical/uterine (none v 8.5%) cancers. When compared with the average stage of detection in the United States, detection was earlier for breast, lung, prostate, and female reproductive cancers. Patient satisfaction rate was 8.35 ± 1.85 (scale 1-10). CONCLUSION: We present a proof of concept study for a one-stop-shop approach to cancer screening in a multidisciplinary outpatient clinic. We successfully detected cancers at an early stage, which has the potential to reduce morbidity and mortality as well as offer substantial cost savings.[Media: see text].

G-EYE colonoscopy is superior to standard colonoscopy for increasing adenoma detection rate: an international randomized controlled trial (with videos).

BACKGROUND AND AIMS: Colorectal cancer (CRC) is largely preventable with routine screening and surveillance colonoscopy; however, interval cancers arising from precancerous lesions missed by standard colonoscopy still occur. An increased adenoma detection rate (ADR) has been found to be inversely associated with interval cancers. The G-EYE device includes a reusable balloon integrated at the distal tip of a standard colonoscope, which flattens haustral folds, centralizes the colonoscope's optics, and reduces bowel slippage. The insufflated balloon also aims to enhance visualization of the colon during withdrawal, thereby increasing the ADR. METHODS: In this randomized, controlled, international, multicenter study (11 centers), patients (aged ≥50 years) referred to colonoscopy for screening, surveillance, or changes in bowel habits were randomized to undergo either balloon-assisted colonoscopy by using an insufflated balloon during withdrawal or standard high-definition colonoscopy. The primary endpoint was the ADR. RESULTS: One thousand patients were enrolled between May 2014 and September 2016 to undergo colonoscopy by experienced endoscopists; 803 were finally analyzed (standard colonoscopy n = 396; balloon-assisted colonoscopy n = 407). Baseline parameters were similar in both groups. Balloon-assisted colonoscopy provided a 48.0% ADR compared with 37.5% in the standard colonoscopy group (28% increase; P = .0027). Additionally, balloon-assisted colonoscopy provided for a significant increase in detection of advanced (P = .0033) flat adenomas (P < .0001) and sessile serrated adenomas/polyps (P = .0026). CONCLUSION: Balloon-assisted colonoscopy yielded a higher ADR and increased the detection of advanced, flat, and sessile serrated adenomas/polyps when compared with standard colonoscopy. Improved detection by the G-EYE device could impact the quality of CRC screening by reducing miss rates and consequently reducing interval cancer incidence. (Clinical trial registration number: NCT01917513.).

Of mice and men: a novel dietary supplement for the treatment of ulcerative colitis.

BACKGROUND: Curcumin, green tea polyphenols and selenium possess anti-inflammatory and anti-oxidant properties. Individually they have demonstrated some efficacy in animal models and human subjects with inflammatory bowel disease (IBD). To evaluate the efficacy and safety of Coltect [Curcumin (500 mg), green tea (250 mg) and selenium (100 µg)] in vivo and in patients with ulcerative colitis (UC). METHODS: Each component was compared to placebo in a DSS mice colitis model. The efficacy was validated in a 2,4,6-trinitrobenzenesulfonic acid (TNBS) rat colitis model. Twenty patients with mild-to-moderate UC received two Coltect tablets twice daily for 8 weeks. Enrollees underwent sigmoidoscopy at study entrance and closure, and physical and laboratory evaluation at baseline, 4 and 8 weeks. RESULTS: Coltect showed a synergistic therapeutic effect in the DSS and TNBS models. Disease activity was significantly higher in the placebo versus the treated group (p < 0.05). Selenium was the more active component. The contribution of green tea was minor. In the TNBS model, the Wallace scores for macroscopic lesions were 4.8 ± 1.5 (treatment) and 8.2 ± 0.5 (placebo) (p = 0.01). In humans, Coltect was well tolerated and effective. Fourteen subjects (70%) improved: nine (45%) went into complete remission, four (20%) experienced marked improvement and one (5%) experienced moderate improvement at the end of the trial. Clinical activity index decreased significantly at 4 and 8 weeks (p < 0.001). Two patients had no change in their symptoms, and one withdrew after 4 weeks. Flare-up in four subjects caused three to withdraw from the study after less than 4 weeks. Endoscopic improvement was observed in 11 (69%) patients, and four patients (25%) achieved complete remission. CONCLUSIONS: Coltect may serve as a first-line or add-on therapy in patients with mild-to-moderate UC.

Prevalence of colorectal neoplasms in young, average risk individuals: A turning tide between East and West.

AIM: To determine the prevalence of colorectal neoplasia in average risk persons 40-59 years of age in Israel and to compare the results with other populations. METHODS: We reviewed the results of asymptomatic average-risk subjects, aged 40 to 59 years, undergoing their first screening colonoscopy between April 1994 and January 2014. The detection rates of adenoma, advanced adenoma (AA) and colorectal cancer (CRC) were determined in the 40's and 50's age groups by gender. The prevalence of lesions was compared between age groups. After meticulous review of the literature, these results were compared to published studies addressing the prevalence of colorectal neoplasia in similar patient groups, in a variety of geographical locations. RESULTS: We included first screening colonoscopy results of 1750 individuals. The prevalence of adenomas, AA and CRC was 8.3%, 1.0% and 0.2% in the 40-49 age group and 13.7%, 2.4% and 0.2% in the 50-59 age group, respectively. Age-dependent differences in adenoma and AA rates were significant only among men (P < 0.005). Literature review disclosed 17 relevant studies. As expected, in both Asian and Western populations, the risks for overall adenoma and advanced adenoma was significantly higher in the 50's age group as compared to the 40's age group in a similar fashion. The result of the current study were similar to previous studies on Western populations. A substantially higher rate of adenoma, was observed in studies conducted among Asian populations in both age groups. CONCLUSION: The higher rate of colorectal neoplasia in Asian populations requires further investigation and reconsideration as to the starting age of screening in that population.

Feasibility study of minimal prepared hydroflush screening colonoscopy.

BACKGROUND: Although screening colonoscopy is effective for early detection of colorectal cancer (CRC), screening rates remain low. Multiple factors are thought to be responsible for the low rates of screening colonoscopy, but bowel preparation appears to be a key deterrent. Tolerability issues with bowel preparations may lead to poor patient compliance, inadequate colon cleansing, and reduced detection of colonic polyps. AIM: The aim of this article is to evaluate the feasibility, safety, and outcomes of minimally prepared intra-procedural hydroflush technique as an alternative to traditional bowel preparation in screening colonoscopy. DESIGN: We conducted a prospective feasibility study of intraprocedural hydroflush technique aided by water-jet pumps and a mechanical suction novel device following minimal bowel preparation for CRC screening. PATIENTS AND METHODS: Nine procedures were performed in nine healthy individuals scheduled for routine screening colonoscopy. Preparation included mild diet restriction, laxative tablets two to three days prior to the procedure and two Fleet enemas one to two hours before the colonoscopy. The cleanliness of the colon was assessed by using the Boston bowel preparation scale. Insertion and withdrawal times were recorded. RESULTS: Complete colonoscopy to the cecum was performed in all patients (100%). Mean time to the cecum was 5.78 ± 2.68 minutes, and mean withdrawal time was 15.33 ± 3.94 minutes. Endoscopic visualization of the entire mucosa was achieved in all cases with no colonoscopy repeated because of inadequate preparation. Four polyps have been detected and removed in three patients. Mild mucosal erosions were seen in some areas where the suction was used extensively, similar to those that can be seen during conventional colonoscopy. Mild stiffness of the shaft of the scope was noted. LIMITATIONS: This was an uncontrolled feasibility study of selected patients. CONCLUSIONS: Minimally prepared colonoscopy with the intra-procedural hydroflush technique for colorectal screening is feasible. The water exchange technology compensates for the mild stiffness of the scope. This technique might increase patients' compliance for CRC screening.

The APC I1307K allele conveys a significant increased risk for cancer.

This study is the first attempt to evaluate the association between the APC I1307K variant and overall cancer risk. It is unique in both its large sample size and in the reliability of data in the control group. The findings described in this article have major implications in terms of identifying asymptomatic individuals who are at increased risk to harbor cancer and therefore targeted to be enrolled in specific early detection and prevention programs. The prevalence of the APC I1307K missense mutation among Ashkenazi Jews is ∼ 6%. Carriers are at an increased risk for colorectal neoplasia. In this study, we examined the association of this variant with non-colorectal cancers. Consecutive 13,013 healthy subjects who underwent screening at the Integrated Cancer Prevention Center between 2006 and 2014 were enrolled. This population was supplemented with 1,611 cancer patients from the same institution. Demographics, medical history, and pathological data were recorded. Mortality data were obtained from the Ministry of Health's registry. The prevalence of APC I1307K in cancer patients and healthy subjects was compared. The APC I1307K variant was detected in 189 (11.8%) cancer patients compared to 614 (4.7%) healthy subjects, reflecting an adjusted age and sex odds ratio (OR) of 2.53 (p < 0.0001). History of two or more cancer types was associated with a positive carrier prevalence (OR = 4.38 p < 0.0001). Males had significantly increased carrier prevalence in lung, urologic, pancreatic, and skin cancers. The carrier prevalence among females was significantly higher only in breast and skin cancers. Female carriers developed cancer at a significantly older age compared to non-carriers (average 62.7 years vs. 57.8, respectively, p = 0.027), had better survival rates (HR = 0.58, p = 0.022) and overall increased longevity (average age of death 78.8 vs. 70.4 years, respectively, p = 0.003). In conclusion, the APC I1307K variant is a reliable marker for overall cancer risk (OR 2.53). Further studies are needed to evaluate its use for specific cancer types-particularly in males. Female carriers have better prognosis and increased lifespan.

Association of CD24 and the adenomatous polyposis coli gene polymorphisms with oral lichen planus.

OBJECTIVE: CD24 and the adenomatous polyposis coli (APC) gene polymorphisms are known to predispose to malignant disease. We aimed to investigate their association with risk and susceptibility of oral lichen planus (OLP) in an Israeli Jewish population. STUDY DESIGN: The study included 54 patients, of which 41 were females (75.9%) and 13 males (24.1%); of the 533 controls, 224 were females (42.0%) and 309 males (57.9%). Genotyping was performed. Two APC (I1307 K, E1317 Q) and four CD24 variants--C170 T (rs52812045), TG1527 del (rs3838646), A1626 G (rs1058881), and A1056 G (rs1058818)--were assessed. Frequencies were analyzed using the Chi-square test. Two-sided P < .05 values were considered significant. Odds ratios and 95% confidence intervals were obtained by logistic regression analyses. RESULTS: CD24 A1056 G carriers have a significantly lower risk of OLP compared with individuals with the wild-type variant (P = .001). A significantly lower risk was found for heterozygote (P = .008) and homozygote carriers (P = .002). Homozygote CD24 A1626 G carriers had a significant higher risk for OLP compared with nonhomozygote carriers (P = .040). CD24 C170 T, TG1527 del, and APC polymorphisms did not show significant associations with OLP risk. CONCLUSIONS: CD24 A1626 G is more frequent in OLP patients, contributes to disease risk, and could play a role in OLP susceptibility. A significant association between CD24 A1056 G and a lower OLP incidence was found, suggesting that it may confer protection against OLP risk and progression.

Predictive Levels of CD24 in Peripheral Blood Leukocytes for the Early Detection of Colorectal Adenomas and Adenocarcinomas.

CD24 is expressed in 90% of colorectal adenomas and adenocarcinomas. Colorectal cancer (CRC) can be mostly prevented but average risk population screening by stool testing or colonoscopy faces many hurdles. Blood testing is clinically needed. We aimed to evaluate the utility of CD24 expression in peripheral blood leukocytes (PBLs). Two independent case studies were conducted in eligible individuals undergoing colonoscopy. Protein extracted from PBLs was subjected to immunoblotting using anti-CD24 monoclonal antibodies. CD24 sensitivity and specificity were determined using receiver operating characteristic (ROC) analysis. Initially, 150 subjects were examined: 63 had CRC, 19 had adenomas, and 68 had normal colonoscopies. The sensitivity and specificity of CD24 for distinguishing CRC from normal subjects were 70.5% (95% CI, 54.8-83.2%) and 83.8% (95% CI, 74.6-92.7%) and for adenomas 84.2% (95% CI, 60.4-96.4%) and 73.5% (95% CI, 61.4-83.5%), respectively. In the second trial (n = 149), a similar specificity but higher sensitivity was achieved: 80.0% (95% CI, 63.1-91.6%) for CRC and 89.2% (95% CI, 74.6-97%) for adenomas. A simple noninvasive blood test evaluating CD24 levels has high sensitivity and specificity for detecting colorectal adenomas and cancer in patients undergoing colonoscopy at an urban medical center. Larger multicenter studies are warranted to establish the potential of this promising test.

Comparison of adenoma detection and miss rates between a novel balloon colonoscope and standard colonoscopy: a randomized tandem study.

BACKGROUND AND STUDY AIMS: Although colonoscopy is the "gold standard" for colorectal cancer screening, a significant number of adenomas are still missed during standard colonoscopy, often because they are hidden behind colonic folds and flexures. The aim of this study was to assess the ability of a novel balloon colonoscope (G-EYE endoscope; Smart Medical Systems, Ra'anana, Israel) to increase adenoma detection and reduce the miss rate compared with standard colonoscopy. PATIENTS AND METHODS: This was a multicenter, randomized, prospective, controlled study in patients (age ≥ 40 years) undergoing colonoscopy for screening or diagnostic work-up (including surveillance). Patients underwent same-day, back-to-back tandem colonoscopy. Patients in Group A underwent standard colonoscopy followed by balloon colonoscopy, and patients in Group B underwent balloon colonoscopy followed by the standard technique. The adenoma detection and miss rates were compared between the two colonoscopy procedures. RESULTS: A total of 126 patients were enrolled and randomized into Group A (n = 60) or Group B (n = 66). The adenoma miss rate of balloon colonoscopy was significantly lower than that of standard colonoscopy (7.5 % vs. 44.7 %; P = 0.0002). The detection of additional adenomas by balloon colonoscopy was significant (81.0 %; P = 0.0002), in particular, the relative amount of adenomas detected in the ascending colon by balloon colonoscopy was 41 % versus 14 % for standard colonoscopy. CONCLUSIONS: A novel balloon colonoscopy technique detected significantly more adenomas than standard colonoscopy, and missed fewer adenomas. Balloon colonoscopy has the potential to increase the effectiveness of colorectal cancer screening and surveillance colonoscopy.

Incidence of colorectal neoplasms among male pilots.

AIM: To assess the prevalence of colorectal neoplasms (adenomas, advanced adenomas and colorectal cancers) among Israeli military and commercial airline pilots. METHODS: Initial screening colonoscopy was performed on average-risk (no symptoms and no family history) airline pilots at the Integrated Cancer Prevention Center (ICPC) in the Tel-Aviv Medical Center. Visualized polyps were excised and sent for pathological examination. Advanced adenoma was defined as a lesion >10 mm in diameter, with high-grade dysplasia or villous histology. The results were compared with those of an age- and gender-matched random sample of healthy adults undergoing routine screening at the ICPC. RESULTS: There were 270 pilots (mean age 55.2 ± 7.4 years) and 1150 controls (mean age 55.7 ± 7.8 years). The prevalence of colorectal neoplasms was 15.9% among the pilots and 20.6% among the controls (P = 0.097, χ (2) test). There were significantly more hyperplastic polyps among pilots (15.5% vs 9.4%, P = 0.004) and a trend towards fewer adenomas (14.8% vs 20.3% P = 0.06). The prevalence of advanced lesions among pilots and control groups was 5.9% and 4.7%, respectively (P = 0.49), and the prevalence of cancer was 0.7% and 0.69%, respectively (P = 0.93). CONCLUSION: There tends to be a lower colorectal adenoma, advanced adenoma and cancer prevalence but a higher hyperplastic polyp prevalence among pilots than the general population.

Role of CD24 polymorphisms in the susceptibility to inflammatory bowel disease.

BACKGROUND: Inflammatory bowel disease (IBD) results from an inappropriate inflammatory response in which genetic, immune, and environmental factors all play important roles. Recently, single nucleotide polymorphisms (SNPs) in the CD24 gene have been associated with the development of several autoimmune diseases. AIM: To evaluate whether CD24 SNPs, are associated with risk of ulcerative colitis (UC) and Crohn's disease (CD). METHODS: The CD24 polymorphisms C170T (rs8734), TG1527del (rs3838646), A1626G (rs1058881), and A1056G (rs1058818) were assessed in a case-control study of an Israeli cohort comprising 117 IBD patients and 105 age and gender-matched healthy controls. Restriction fragment length polymorphism (RFLP) analysis was performed using BstX1, Bsr1, Mfe1, and BstU1 restriction enzymes. Odds ratios (OR) and 95% confidence intervals (CI) were estimated by logistic regression models. RESULTS: Carriers of the C170T SNP were at increased risk of IBD (OR=3.022, 95% CI: 1.748-5.223, p=0.001), UC (OR=3.002, 95% CI: 1.661-5.427, p=0.001) and CD (OR=3.077, 95% CI: 1.334-7.095, p=0.008). Carrying the A1626G and A1056G SNPs was found to be a risk factor for IBD (OR=2.460, 95% CI: 1.420-4.259, p=0.001 and OR=1.856, 95% CI: 1.011-3.405, p=0.01), UC (OR=2.218, 95% CI: 1.207-4.075, p=0.01 and OR=1.944, 95% CI: 0.995-3.798, p=0.01) but not for CD (p=0.086 and p=0.299). The A1626G and TG1527del were found to be associated with younger age of IBD onset (p=0.022 and p=0.027, respectively). CONCLUSIONS: The CD24 C170T polymorphism is associated with IBD risk. The A1626G and A1056G SNPs might be associated only with UC risk. These findings suggest CD24 as a new genetic susceptibility factor, with clinical implications in the prediction of IBD prognosis and therapy.

One stop screening for multiple cancers: the experience of an integrated cancer prevention center.

BACKGROUND: Cancer is a leading cause of mortality worldwide. Screening is a key strategy for reducing cancer morbidity and mortality. METHODS: We aimed to describe the experience of an integrated cancer prevention center in screening an asymptomatic population for the presence of neoplasia. One-thousand consecutive asymptomatic, apparently healthy adults, aged 20-80 years, were screened for early detection of 11 common cancers that account for 70-80% of cancer mortality. RESULTS: Malignant and benign lesions were found in 2.4% and 7.1% of the screenees, respectively. The most common malignant lesions were in the gastrointestinal tract and breast followed by gynecological and skin. The compliance rate for the different screening procedures was considerably higher than the actual screening rate in the general Israeli population - 78% compared to 60% for mammography (p<0.001) and 39% compared to 16% for colonoscopy (p<0.001). Advanced age, family history of cancer and certain lifestyle parameters were associated with increased risk. Moreover, polymorphisms in the APC and CD24 genes indicated high cancer risk. When two of the polymorphisms existed in an individual, the risk for a neoplastic lesion was extremely high (OR 2.3 [95% CI 0.94-5.9]). CONCLUSIONS: One stop shop screening for 11 common cancers in the setting of a multidisciplinary outpatient clinic is feasible and can detect cancer at an early stage.

Gender-associated differences in urea breath test for Helicobacter pylori infection referrals and results among dyspeptic patients.

AIM: To verify whether there is a gender difference in the (13)C-urea breath test results in a large cohort. METHODS: The test results of dyspeptic patients referred for (13)C-urea breath testing between January and December, 2007 were evaluated. Testing was carried out at the health insurance organization branches and evaluated at a central laboratory in Israel. RESULTS: Of a total of 28 746 test results, 18 122 (63.04%) were from females and 10 624 (36.95%) from males. Overall, 10 188 (35.4%) results [expressed as delta over baseline (DOB)] were positive (DOB (13)C > 5), 18,326 (63.7%) were negative (DOB (13)C < 3.5) and 232 (0.8%) were borderline (DOB (13)C 3.5-5). There was a significant difference between the total positive rate among females and males (34.8% vs 37.2%, respectively, P = 0.0003). The mean test value was increased by approximately 10 units for females compared to males (P < 0.01) and this difference was consistent for all age groups (i.e., between 10-80 years of age, P < 0.01). CONCLUSION: More females were referred to (13)C-urea breath testing. More males had positive results. The mean test values were significantly higher among females of all age groups, possibly representing an increased bacterial load among females and suggesting gender-associated differences in Helicobacter pylori host interactions.

The role of low-dose aspirin in the prevention of colorectal cancer.

INTRODUCTION: Colorectal cancer (CRC) is a prevalent disease that is associated with considerable morbidity and mortality. The progression of normal mucosa through adenomatous polyps to overt cancer can span for 10 - 15 years, making early detection, as well as the use of chemopreventive agents such as aspirin, an attractive option. The effects of aspirin in reducing CRC incidence and mortality have consistently been demonstrated in a number of studies. However, a greater understanding of how aspirin exerts its anti-cancer effects is warranted. AREAS COVERED: The aim of this non-systematic review, which was developed using published randomized and epidemiological studies, as well as key references known to the authors, was to consider the role of aspirin in CRC prevention. Areas covered include the effects of aspirin on cardiovascular disease, CRC and colorectal adenoma (CRA) prevention, mode of action of aspirin and the benefit-to-risk of aspirin in disease prevention. EXPERT OPINION: Incorporating CRC and CRA benefits into coronary heart disease (CHD) risk scores would be particularly useful for determining the benefit-to-risk ratio for aspirin use in borderline cases. For instance, patients with an annual CHD risk around 0.7 - 1.4%, but with a high risk of colorectal neoplasm may benefit from aspirin. The strong association between CRC and age may also be useful for re-examining the benefit-to-risk ratio for aspirin use in older patients. However, it has to be noted that a cancer prevention indication for aspirin is not approved regulatory-wise anywhere.

[Surveillance of patients with Barrett's esophagus].

Barret's esophagus (BE) is defined as a situation in which the distal esophageal squamous epithelium was replaced by columnar epithelium, with or without goblet cells. BE is considered a significant risk factor for the development of esophageal cancer, however, screening is recommended only for high risk patients. The new guidelines determine the proper terminology of the endoscopic appearance of BE and the way that biopsies should be taken. After BE is confirmed, surveillance is extremely important as its performance has been shown to prevent cancer and death. The surveillance is based on the endoscopic and pathological findings, highlighting the importance of advanced endoscopy and specialized pathology expertise. The guidelines determine the place of the endoscopic ablative technology and specialized surgery in these patients.

[Surveillance of patients with inflammatory bowel diseases].

This position paper of the Section of Gastrointestinal Oncology of the Israeli Gastroenterological Association recommends specific guidelines for colorectal cancer surveillance in patients with inflammatory bowel disease. Colorectal cancer (CRC) is a severe complication of inflammatory bowel disease (IBD), generally developing into a longstanding disease. The Lifetime prevalence of CRC in ulcerative colitis (UC) patients is estimated to be 2% after 10 years, 8% after 20 years, and even 18% after 30 years of extensive disease. Screening colonoscopy should be initiated 8-10 years after onset of symptoms in extensive UC patients (pancolitis), and after 15 years in patients with left-sided colitis (UC or Crohn's). Surveillance should continue periodically at an interval of every 1 to 2 years. Surveillance colonoscopies should be performed in combination with an extensive biopsy protocol. High-grade dysplasia (HGD) in flat mucosa or a dysplasia associated Lesion or mass (DALM) is considered an indication for colectomy when the pathological findings are confirmed by a second experienced pathologist. Further research is directed toward improving detection of dysplasia during colonoscopy through the use of novel endoscopic imaging techniques which are hoped to impact the approach to cancer prevention in patients with IBD.

[Management of hereditary non-polyposis syndrome (Lynch syndrome)].

Genetic background is suspected in about 20% of colorectal cancer (CRC) cases, in which either genetic polymorphisms or Mendelian heritable factors are involved. Currently known CRC syndromes include various polyposis syndromes (<1% of total CRC cases) and Lynch syndrome (LS), previously termed hereditary nonpolyposis colorectal cancer (HNPCC, comprises 3-5% of all CRC cases). LS is caused by dominantly inherited mutations in the mismatch repair genes MLH1, MSH2, MSH6 or PMS2, and results in a very high lifetime risk (approximately 80%) for CRC and significantly increased risk for extracolonic tumors in regions such as the endometrium, ovary, urinary tract, lymphoma, stomach, pancreas small bowel and brain. Carriers are advised to undergo specific medical and intense endoscopic surveillance. Diagnosis of carriers is mandatory for providing appropriate recommendations for surveillance, which was shown to decrease morbidity, mortality and health costs. Diagnosis of LS dictates preventive surgical procedures for the colon endometrium and ovaries, and assists in decisions regarding CRC chemotherapy. Family members' screening and surveillance is determined by mutation testing. Diagnosis is performed, based on the clinical selection criteria of Amsterdam and Bethesda and according to typical histology of tumor tissue. Initially, tumor testing is performed by either microsatellite instability (MSI), immunohistochemistry (IHC) or both. Certain Jewish ethnical subgroups may undergo founder mutation testing. Ultimate identification of the mutation by sequencing and MLPA is performed according to the IHC results. In families with hereditary CRC criteria, in which workup for LS is negative, the surveillance protocol will be determined by an experienced multidisciplinary team, including a formal genetic consultation.