Colorectal cancer screening at age 45 years in Israel: Cost-effectiveness and global implications.

BACKGROUND: Colorectal cancer (CRC) incidence at ages <50 years is increasing worldwide. Screening initiation was lowered to 45 years in the United States. The cost-effectiveness of initiating CRC screening at 45 years in Israel was assessed with the aim of informing national policy and addressing internationally relevant questions. METHODS: A validated CRC screening model was calibrated to Israeli data and examined annual fecal immunochemical testing (FIT) or colonoscopy every 10 years from 45 to 74 years (FIT45-74 or Colo45-74) versus from 50 to 74 years (FIT50-74 or Colo50-74). The addition of a fourth colonoscopy at 75 years was explored, subanalyses were performed by sex/ethnicity, and resource demands were estimated. RESULTS: FIT50-74 and Colo50-74 reduced CRC incidence by 57% and 70% and mortality by 70% and 77%, respectively, versus no screening, with greater absolute impact in Jews/Other versus Arabs but comparable relative impact. FIT45-74 further reduced CRC incidence and mortality by an absolute 3% and 2%, respectively. With Colo45-74 versus Colo50-74, CRC cases and deaths increased slightly as three colonoscopies per lifetime shifted to 5 years earlier but mean quality-adjusted life-years gained (QALYGs) per person increased. FIT45-74 and Colo45-74 cost 23,800-53,900 new Israeli shekels (NIS)/QALYG and 110,600-162,700 NIS/QALYG, with the lowest and highest values among Jewish/Other men and Arab women, respectively. A fourth lifetime colonoscopy cost 48,700 NIS/QALYG. Lowering FIT initiation to 45 years with modest participation required 19,300 additional colonoscopies in the first 3 years. CONCLUSIONS: Beginning CRC screening at 45 years in Israel is projected to yield modest clinical benefits at acceptable costs per QALYG. Despite different estimates by sex/ethnicity, a uniform national policy is favored. These findings can inform Israeli guidelines and serve as a case study internationally.

Genetic testing for assessment of lynch syndrome in young patients with polyps.

BACKGROUND: Routine screening for establishing Lynch syndrome (LS) in young individuals diagnosed with adenomas is not recommended due to its low yield, and limited sensitivity of the employment of immunohistochemistry for DNA mismatch-repair proteins on polyps. Hence we aimed to evaluate the yield of germline mutational analysis in diagnosis of LS in a young Israeli cohort with colorectal adenomatous polyps. METHODS: Data were retrospectively collected on consecutive patients, age ≤ 45 years, who underwent colonoscopy with removal of at least one adenoma during 2015-2020, and subsequently genetic testing by multigene panel or LS-Jewish founder mutation panel. RESULTS: Overall, 92 patients were included (median age 35 years, range 23-45 years), of whom 79 (85.8%) underwent multigene panel genotyping, and 13 (14.2%) analysis for Jewish founder LS gene mutations. Altogether, 18 patients were identified with pathogenic mutations in actionable genes, including LS-associated genes in 6 (6.5%), BRCA2 in 2 (2.5%), GREM1 in 1(1.2%), and low-penetrance genes- APC I1307K and CHEK2- in 9 (11.4%) patients. Compared with non-LS patients, LS-carriers had a significantly higher median PREMM5 score (2.6 vs. 1.3; P = 0.04). CONCLUSIONS: Young individuals diagnosed with adenomatous polyps should be offered genetic testing when fulfilling clinical guidelines for LS, but weight should also be given to adenoma characteristics in the PREMM5 score.

Establishing an integrated gastroenterology service between a medical center and the community.

AIM: To combine community and hospital services in order to enable improvements in patient management, an integrated gastroenterology service (IGS) was established. METHODS: Referral patterns to specialist clinics were optimized; open access route for endoscopic procedures (including esophago-gastro-duodenoscopy, sigmoidoscopy and colonoscopy) was established; family physicians' knowledge and confidence were enhanced; direct communication lines between experts and primary care physicians were opened. Continuing education, guidelines and agreed instructions for referral were promoted by the IGS. Six quality indicators were developed by the Delphi method, rigorously designed and regularly monitored. Improvement was assessed by comparing 2010, 2011 and 2012 indicators. RESULTS: An integrated delivery system in a specific medical field may provide a solution to a fragmented healthcare system impaired by a lack of coordination. In this paper we describe a new integrated gastroenterology service established in April 2010. Waiting time for procedures decreased: 3 mo in April 30th 2010 to 3 wk in April 30th 2011 and stayed between 1-3 wk till December 30th 2012. Average cost for patient's visit decreased from 691 to 638 NIS (a decrease of 7.6%). Six health indicators were improved significantly comparing 2010 to 2012, 2.5% to 67.5%: Bone densitometry for patients with inflammatory bowel disease, preventive medications for high risk patients on aspirin/NSAIDs, colonoscopy following positive fecal occult blood test, gastroscopy in Barrett's esophagus, documentation of family history of colorectal cancer, and colonoscopy in patients with a family history of colorectal cancer. CONCLUSION: Establishment of an IGS was found to effectively improve quality of care, while being cost-effective.

Body mass index and socioeconomic status measured in adolescence, country of origin, and the incidence of gastroesophageal adenocarcinoma in a cohort of 1 million men.

BACKGROUND: To the authors' knowledge, little work has been done concerning adolescent precursors for gastroesophageal cancer. In the current study, the association of adolescent overweight as well as socioeconomic status (SES) with the incidence of esophageal adenocarcinoma (EAC), gastroesophageal junction adenocarcinoma (GEJAC), and noncardia gastric cancer (NCGC) was evaluated. METHODS: Body mass index (BMI) was measured in 1 million Israeli adolescent males who underwent a general health examination at a mean age of 17.3 ± 0.5 years from 1967 to 2005. Overweight was defined as a BMI ≥ 85th percentile of the standard US distribution in adolescence. Incident cancer was identified by linkage with the Israeli National Cancer Registry. RESULTS: A total of 182 incident cancer cases were documented (52 combined EAC and GEJAC cases and 130 NCGC cases). Adolescent overweight at baseline (BMI ≥ 85th percentile) was associated with an increased risk in the combined group of cases of EAC and GEJAC (multivariable hazards ratio [HR], 2.1; 95% confidence interval [95% CI], 1.1-4.3 [P = .032]). Low SES (the lowest category vs the highest) as well as low number of years of education (≤ 9 years) were associated with an increased risk of intestinal-type NCGC (multivariable HR, 2.2; 95% CI, 1.0-4.8 [P = .041] and multivariable HR, 1.9; 95% CI, 1.1-3.19 [P = .020], respectively). The adjusted risk of NCGC was higher in immigrants born in Asian countries and the former Soviet Union. CONCLUSIONS: Overweight during adolescence was found to be substantially associated with the subsequent development of EAC and GEJAC. In addition, although potential confounding by Helicobacter pylori infection status or lifestyle factors was not fully accounted for in the analyses, lower SES as well as immigration from higher-risk countries are important determinants of NCGC.

Factors affecting compliance in faecal occult blood testing: a cluster randomized study of the faecal immunochemical test versus the guaiac faecal occult test.

OBJECTIVE: To compare the uptake of faecal immunochemical occult blood test (FIT) with guaiac faecal occult blood test (gFOBT) in a screening programme, with specific attention to the demographic and socioeconomic factors that might affect test uptake. SETTING: The Clalit Health Service screening programme, Israel. METHODS: Average-risk individuals aged 50-75 years were randomized into a FIT arm or gFOBT arm using a programme based on the socioeconomic status (SES) of their primary care clinics. G-FOBT was performed with Hemoccult SENSA™ (3 evacuations) and FIT with the OC- MICRO(TM) (3 evacuations, refrigerating mandated). The GLIMMIX model was used. RESULTS: There were 5,464 and 10,668 eligible participants in the FIT and gFOBT arms respectively. Compliance in taking the kits was better (but not statistically significantly better) with gFOBT (37.8% vs. 29.3%; odds ratio [OR] 1.43 [95% CI 0.73-2.80]; P = 0.227). Kit return was higher in the FIT arm (65.0% vs. 78.9%; OR 0.45 [95% CI 0.24-0.83], P = 0.021). Overall test uptake was affected by age, gender, being immigrant and SES (determined by whether or not the participant paid national insurance tax, and the SES of the primary care clinic). The overall uptake of gFOBT and FIT was comparable (OR 0.996 [95% CI 0.46-2.17], P = 0.99). CONCLUSIONS: Overall compliance for test uptake was comparable between the two methods despite the more demanding procedure in the FIT arm. Sociodemographic parameters were the major determinants of compliance. An educational programme, with emphasis on the sociodemographic characteristics of the target population, should be instigated.

Assessment and validation of the new capsule endoscopy Crohn's disease activity index (CECDAI).

BACKGROUND: Capsule endoscopy is a relatively new imaging tool for the detection of small bowel pathology. The assessment of the severity of Crohn's disease by capsule endoscopy is not standardized and is limited by interobserver variations in interpreting the findings. AIM: To develop, assess and validate a new, simple capsule endoscopy Crohn's disease activity index (CECDAI) in order to grade the severity of small bowel capsule endoscopy findings. METHODS: The system involves dividing the small bowel into proximal and distal segments according to transit time and then rating each segment on the basis of three parameters: inflammation (A), extent of disease (B) and presence of strictures (C). The segmental score is calculated by multiplying the inflammation subscore by the disease-subextent score and adding the stricture subscore (A x B + C); the final score is calculated by adding the two segmental scores: CECDAI = (A1 x B1 + C1) + (A2 x B2 + C2). In the present study, four senior endoscopists (two with experience in capsule endoscopy interpretation) independently reviewed coded capsule endoscopy videos of 20 patients with Crohn's disease and rated them according to the CECDAI. Interobserver variability was analyzed by Spearman's correlation test. RESULTS: The CECDAI total scores for the 20 patients ranged from 0 to 26. The correlation for the total score assigned between every two observers was 0.867 (0.700-1.000 = strong degree association; WHO classification; P < 0.0001). The Kappa statistics for agreement among all observers for the subscores and total scores were as follows: A1, 0.31 +/- 0.05; B1, 0.25 +/- 0.05; C1 (no cases); A2, 0.51 +/- 0.05; B2, 0.57 +/- 0.05; C2, 0.27 +/- 0.07. All examiners reported that the system was simple to learn and apply. CONCLUSIONS: The CECDAI score may serve as a convenient, reliable and reproducible diagnostic and follow-up tool for use by experienced endoscopists in the evaluation of patients with Crohn's disease of the small bowel.