Low Colorectal Cancer Risk After Resection of High-Risk Pedunculated Polyps.

BACKGROUND: Post-fecal immunochemical test (FIT) colonoscopy represents a setting with an enriched prevalence of advanced adenomas. Due to an expected higher risk of colorectal cancer (CRC), postpolypectomy surveillance is recommended, generating a substantially increased load on endoscopy services. The aim of our study was to investigate postpolypectomy CRC risk in a screening population of FIT+ subjects after resection of low-risk adenomas (LRAs) or high-risk adenomas (HRAs). METHODS: We retrieved data from a cohort of patients undergoing postpolypectomy surveillance within a FIT-based CRC screening program in Italy between 2002 and 2017 and followed-up to December 2021. Main outcomes were postpolypectomy CRC incidence and mortality risks according to type of adenoma (LRA/HRA) removed at colonoscopy as well as morphology, size, dysplasia, and location of the index lesion. We adopted as comparators FIT+/colonoscopy-negative and FIT- patients. The absolute risk was calculated as the number of incident CRCs per 100,000 person-years of follow-up. We used Cox multivariable regression models to identify associations between CRC risks and patient- and polyp-related variables. RESULTS: Overall, we included 87,248 post-FIT+ colonoscopies (133 endoscopists). Of these, 42,899 (49.2%) were negative, 21,650 (24.8%) had an LRA, and 22,709 (26.0%) an HRA. After a median follow-up of 7.25 years, a total of 635 CRCs were observed. For patients with LRAs, CRC incidence (hazard ratio [HR], 1.18; 95% confidence interval [CI], 0.92-1.53) was not increased compared with the FIT+/colonoscopy-negative group, while for HRAs a significant increase in CRC incidence (HR, 1.53; 95% CI, 1.14-2.04) was found. The presence of 1 or more risk factors among proximal location, nonpedunculated morphology, and high-grade dysplasia explained most of this excess CRC risk in the HRA group (HR, 1.85; 95% CI, 1.36-2.52). Patients with only distal pedunculated polyps without high-grade dysplasia, representing 39.2% of HRA, did not have increased risk compared with the FIT- group (HR, 0.87; 95% CI, 0.59-1.28). CONCLUSIONS: CRC incidence is significantly higher in patients with HRAs diagnosed at colonoscopy. However, such excess risk does not appear to apply to patients with only distal pedunculated polyps without high-grade dysplasia, an observation that could potentially reduce the burden of surveillance in FIT programs.

Adenoma Detection Rate and Colorectal Cancer Risk in Fecal Immunochemical Test Screening Programs : An Observational Cohort Study.

BACKGROUND: Colorectal cancer (CRC) screening programs based on fecal immunochemical tests (FITs) represent the standard of care for population-based interventions. Their benefit depends on the identification of neoplasia at colonoscopy after FIT positivity. Colonoscopy quality measured by adenoma detection rate (ADR) may affect screening program effectiveness. OBJECTIVE: To examine the association between ADR and postcolonoscopy CRC (PCCRC) risk in a FIT-based screening program. DESIGN: Retrospective population-based cohort study. SETTING: Fecal immunochemical test-based CRC screening program between 2003 and 2021 in northeastern Italy. PATIENTS: All patients with a positive FIT result who had a colonoscopy were included. MEASUREMENTS: The regional cancer registry supplied information on any PCCRC diagnosed between 6 months and 10 years after colonoscopy. Endoscopists' ADR was categorized into 5 groups (20% to 39.9%, 40% to 44.9%, 45% to 49.9%, 50% to 54.9%, and 55% to 70%). To examine the association of ADR with PCCRC incidence risk, Cox regression models were fitted to estimate hazard ratios (HRs) and 95% CIs. RESULTS: Of the 110 109 initial colonoscopies, 49 626 colonoscopies done by 113 endoscopists between 2012 and 2017 were included. After 328 778 person-years follow-up, 277 cases of PCCRC were diagnosed. Mean ADR was 48.3% (range, 23% and 70%). Incidence rates of PCCRC from lowest to highest ADR group were 13.13, 10.61, 7.60, 6.01, and 5.78 per 10 000 person-years. There was a significant inverse association between ADR and PCCRC incidence risk, with a 2.35-fold risk increase (95% CI, 1.63 to 3.38) in the lowest group compared with the highest. The adjusted HR for PCCRC associated with 1% increase in ADR was 0.96 (CI, 0.95 to 0.98). LIMITATION: Adenoma detection rate is partly determined by FIT positivity cutoff; exact values may vary in different settings. CONCLUSION: In a FIT-based screening program, ADR is inversely associated with PCCRC incidence risk, mandating appropriate colonoscopy quality monitoring in this setting. Increasing endoscopists' ADR may significantly reduce PCCRC risk. PRIMARY FUNDING SOURCE: None.

Adenoma detection by Endocuff-assisted versus standard colonoscopy in an organized screening program: the "ItaVision" randomized controlled trial.

BACKGROUND: The Endocuff Vision device (Arc Medical Design Ltd., Leeds, UK) has been shown to increase mucosal exposure, and consequently adenoma detection rate (ADR), during colonoscopy. This nationwide multicenter study assessed possible benefits and harms of using Endocuff Vision in a fecal immunochemical test (FIT)-based screening program. METHODS: Patients undergoing colonoscopy after a FIT-positive test were randomized 1:1 to undergo Endocuff-assisted colonoscopy or standard colonoscopy, stratified by sex, age, and screening history. Primary outcome was ADR. Secondary outcomes were ADR stratified by endoscopists' ADR, advanced ADR (AADR), adenomas per colonoscopy (APC), withdrawal time, and adverse events. RESULTS: 1866 patients were enrolled across 13 centers. After exclusions, 1813 (mean age 60.1 years; male 53.8 %) were randomized (908 Endocuff Vision, 905 standard colonoscopy). ADR was significantly higher in the Endocuff Vision arm (47.8 % vs. 40.8 %; relative risk [RR] 1.17, 95 % confidence interval [CI] 1.06-1.30), with no differences between arms regarding size or morphology. When stratifying for endoscopists' ADR, only low detectors (ADR < 33.3 %) showed a statistically significant ADR increase (Endocuff Vision 41.1 % [95 %CI 35.7-46.7] vs. standard colonoscopy 26.0 % [95 %CI 21.3-31.4]). AADR (24.8 % vs. 20.5 %, RR 1.21, 95 %CI 1.02-1.43) and APC (0.94 vs. 0.77; P  = 0.001) were higher in the Endocuff Vision arm. Withdrawal time and adverse events were similar between arms. CONCLUSION: Endocuff Vision increased ADR in a FIT-based screening program by improving examination of the whole colonic mucosa. Utility was highest among endoscopists with a low ADR.

Recalling pain experienced during a colonoscopy: pain expectation and variability.

OBJECTIVES: This study investigated the relationship between participants' expected levels of pain intensity before a colonoscopy, pain intensity experienced while they were undergoing this medical procedure (real-time pain), and their retrospective evaluation of this experience. DESIGN: Correlational design. Regression analyses were performed and mediational models were tested. METHODS: Ninety patients who were about to undergo a colonoscopy were asked to report the pain intensity on a scale ranging from 0 (no pain) to 10 (extreme pain). They reported the expected intensity of pain before the examination, their real-time intensity of pain every 60 s during the colonoscopy, and their global retrospective evaluation of the pain experienced when the procedure was over. RESULTS: Results confirmed that, regardless of participants' gender, the variability of the real-time pain distribution was a significant predictor of the accuracy of recall (i.e. the discrepancy between recalled pain and mean real-time pain). Moreover, participants' pain expectations preceding the examination were a significant predictor of the accuracy of recall. It was further demonstrated that the effect of patients' expectations on the discrepancy was mediated by the real-time pain variability. CONCLUSIONS: The results of the present study provide useful indications about what the target of interventions aimed at reducing the bias in pain recall should be.

C-JUN and CPP32 (CASPASE 3) in human pancreatic cancer: relation to cell proliferation and death.

INTRODUCTION: There is strong evidence that tumor growth is not only a result of uncontrolled cell proliferation but also of decreased apoptosis. AIMS: To ascertain the expression of c-Jun in specimens of pancreatic duct cancer and to evaluate its correlation with CPP32, apoptotic index, and proliferation index (MIB-1). METHODS: Tissue samples were collected from 23 patients with pancreatic duct cancer who had not received chemotherapy nor radiation therapy before surgery. In these specimens we determined the expression of c-Jun protein, CPP32, and MIB-1 by immunohistochemical method. Apoptosis was studied by the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end labeling method. RESULTS: CPP32/caspase3 was expressed in 83% and c-Jun in 87% of primary lesions. Three of 23 samples were completely negative for c-Jun, and 4 of 23 were negative for CPP32. Three of 4 specimens negative for CPP32 showed low or negative c-Jun. A significant correlation was found between CPP32/caspase3 and c-Jun (r = 0.51; p < 0.01) and between c-Jun and MIB-1 (r = 0.57; p < 0.004). No correlation was found between CPP32, c-Jun, MIB-1, and apoptotic index. CONCLUSIONS: The positive correlation between the expression of c-Jun and CPP32 and the absence of both in the same specimens suggest that a common factor or common factors induce the expression of both genes. Pancreatic cancer tissue with an increased percentage of proliferating tumor cells showed also a strong expression of c-Jun, which supports the hypothesis that this oncogene may be involved in the growth of pancreatic cancer. We hypothesize that under different extracellular stimuli both death and proliferation are activated in neoplastic cell, probably under the control of transcription factor AP-1.

The Effect of Omeprazole on Serum Concentrations of Theophylline, Pepsinogens A and C, and Gastrin in Elderly Duodenal Ulcer Patients.

With the aim of verifying the effect of omeprazole treatment on theophyline serum concentration in elderly peptic ulcer patients, we studied 10 male subjects aged >65 years (mean age = 75.2, range = 67--86) with chronic obstructive bronchopneumonia and endoscopically diagnosed duodenal ulcer in acute phase. All subjects were treated with a slow-release formulation of theophylline 200 mg b.i.d. plus omeprazole 20 mg daily for 4 weeks. In all subjects serum concentrations of azote, creatinine, theophylline were determined at the beginning and after 1 and 4 weeks; at the beginning and end of the study, pepsinogen group A (PGA), pepsinogen group C(PGC) and gastrin were measured. Statistical analysis was performed with the Student's t-test for paired data. The results showed no statistically significant differences after 1 and 4 weeks of omeprazole treatment in serum concentrations of theophylline (T(0) = 7.4, T(1 week) = 7.5, T(4 weeks) = 6.0, p = ns), azote (T(0) = 45.2, T(1 week) = 30.5, T(4 weeks) = 36.1, p = ns), creatinine (T(0) = 1.27, T(1 week) = 1.02, T(4 weeks) = 1.16, p = ns), PGA (T(0) = 99.5, T(4 weeks) = 126.2, p = ns), and PGC (T(0) = 10.6, T(4 weeks) = 12.1, p = ns); however serum gastrin increased from T(0) = 70.2 plus minus 13.2 to T(4 weeks) = 130.3 plus minus 18.3 (p < 0.0001). It was concluded that (1) serum concentration of theophylline is not affected by the concomitant omeprazole treatment lasting 1 month in elderly patients suffering from chronic obstructive bronchopneumonia and peptic ulcer, (2) modifications of dosages of theophylline and/or omeprazole are not necessary in the elderly with normal renal function, (3) the increase in fasting serum gastrin after 4 weeks of treatment may indicate that omeprazole 20 mg daily is efficacious in inhibiting gastric acid secretion in the elderly people.