Baseline Features and Reasons for Nonparticipation in the Colonoscopy Versus Fecal Immunochemical Test in Reducing Mortality From Colorectal Cancer (CONFIRM) Study, a Colorectal Cancer Screening Trial.

Importance: The Colonoscopy Versus Fecal Immunochemical Test in Reducing Mortality From Colorectal Cancer (CONFIRM) randomized clinical trial sought to recruit 50 000 adults into a study comparing colorectal cancer (CRC) mortality outcomes after randomization to either an annual fecal immunochemical test (FIT) or colonoscopy. Objective: To (1) describe study participant characteristics and (2) examine who declined participation because of a preference for colonoscopy or stool testing (ie, fecal occult blood test [FOBT]/FIT) and assess that preference's association with geographic and temporal factors. Design, Setting, and Participants: This cross-sectional study within CONFIRM, which completed enrollment through 46 Department of Veterans Affairs medical centers between May 22, 2012, and December 1, 2017, with follow-up planned through 2028, comprised veterans aged 50 to 75 years with an average CRC risk and due for screening. Data were analyzed between March 7 and December 5, 2022. Exposure: Case report forms were used to capture enrolled participant data and reasons for declining participation among otherwise eligible individuals. Main Outcomes and Measures: Descriptive statistics were used to characterize the cohort overall and by intervention. Among individuals declining participation, logistic regression was used to compare preference for FOBT/FIT or colonoscopy by recruitment region and year. Results: A total of 50 126 participants were recruited (mean [SD] age, 59.1 [6.9] years; 46 618 [93.0%] male and 3508 [7.0%] female). The cohort was racially and ethnically diverse, with 748 (1.5%) identifying as Asian, 12 021 (24.0%) as Black, 415 (0.8%) as Native American or Alaska Native, 34 629 (69.1%) as White, and 1877 (3.7%) as other race, including multiracial; and 5734 (11.4%) as having Hispanic ethnicity. Of the 11 109 eligible individuals who declined participation (18.0%), 4824 (43.4%) declined due to a stated preference for a specific screening test, with FOBT/FIT being the most preferred method (2820 [58.5%]) vs colonoscopy (1958 [40.6%]; P < .001) or other screening tests (46 [1.0%] P < .001). Preference for FOBT/FIT was strongest in the West (963 of 1472 [65.4%]) and modest elsewhere, ranging from 199 of 371 (53.6%) in the Northeast to 884 of 1543 (57.3%) in the Midwest (P = .001). Adjusting for region, the preference for FOBT/FIT increased by 19% per recruitment year (odds ratio, 1.19; 95% CI, 1.14-1.25). Conclusions and Relevance: In this cross-sectional analysis of veterans choosing nonenrollment in the CONFIRM study, those who declined participation more often preferred FOBT or FIT over colonoscopy. This preference increased over time and was strongest in the western US and may provide insight into trends in CRC screening preferences.

Association of trainee participation with adenoma and polyp detection rates.

AIM: To investigate whether adenoma and polyp detection rates (ADR and PDR, respectively) in screening colonoscopies performed in the presence of fellows differ from those performed by attending physicians alone. METHODS: We performed a retrospective review of all patients who underwent a screening colonoscopy at Grady Memorial Hospital between July 1, 2009 and June 30, 2015. Patients with a history of colon polyps or cancer and those with poor colon preparation or failed cecal intubation were excluded from the analysis. Associations of fellowship training level with the ADR and PDR relative to attendings alone were assessed using unconditional multivariable logistic regression. Models were adjusted for sex, age, race, and colon preparation quality. RESULTS: A total of 7503 colonoscopies met the inclusion criteria and were included in the analysis. The mean age of the study patients was 58.2 years; 63.1% were women and 88.2% were African American. The ADR was higher in the fellow participation group overall compared to that in the attending group: 34.5% vs 30.7% (P = 0.001), and for third year fellows it was 35.4% vs 30.7% (aOR = 1.23, 95%CI: 1.09-1.39). The higher ADR in the fellow participation group was evident for both the right and left side of the colon. For the PDR the corresponding figures were 44.5% vs 40.1% (P = 0.0003) and 45.7% vs 40.1% (aOR = 1.25, 95%CI: 1.12-1.41). The ADR and PDR increased with increasing fellow training level (P for trend < 0.05). CONCLUSION: There is a stepwise increase in ADR and PDR across the years of gastroenterology training. Fellow participation is associated with higher adenoma and polyp detection.

Recurrent hematochezia secondary to gastrointestinal stromal tumors (GISTs) in neurofibromatosis type one.

BACKGROUND: Patients with neurofibromatosis type 1 (NF1) suffer from cutaneous, neurological and intestinal complications due to the mutation of the neurofibromin gene and abnormal protein product. Gastrointestinal stromal tumors (GISTs) are relatively rare primary tumors of the stomach and small intestine. Patients with NF1 are prone to developing GISTs. We present a case of recurrent gastrointestinal (GI) bleeding from multiple GISTs in a patient with NF1. CASE: A 42 year-old male with NF1 presented with significant GI bleeding; endoscopies failed to identify the source. Multiple lesions involving the small bowel were seen on laparotomy; he underwent reparative small bowel resection. Pathology showed a well circumscribed spindle cell proliferation with minimal atypia and rare mitoses; immunostaining was positive for CD117 (KIT) and CD34; KIT mutations in exons 9, 11, 13 and 17 were negative. DISCUSSION: Up to 25% of patients with NF1 develop GISTs with non-specific presentations; however they may be a source of significant GI bleeding. The pathology, course and molecular composition of these tumors are different from sporadic GISTs. In NF1, GISTs are usually multiple, located in the small bowel (as opposed to the stomach as in sporadic cases) and occur at a younger age. Their clinical scenario is not unlike other hereditary tumor syndromes-multiple tumors with a 10-20% malignant potential. NF1-associated GISTs almost uniformly do not exhibit gain-of-function activation of KIT or PDGFA (pathogenesis is suggested to be from the loss of heterozygosity of the NF1 gene) and are not likely to respond to imatinib. Multiple means of localizing GISTs exist and capsule endoscopy should be recommended to all NF1 patients as it provides a non-invasive approach to localizing the tumors for further surgical management.

Endoscopic approach to capsule endoscope retention.

In recent years, wireless capsule endoscopy has become increasingly indicated and utilized in the diagnosis and management of small bowel disorders. As such, its most common complication, capsule retention, has become a more frequently encountered clinical entity. Historically, when medical management of capsule retention has failed, patients have been sent directly to surgery. However, recent advances in small bowel enteroscopy have demonstrated a high success rate and safety profile in retrieving retained capsules. These approaches appear to be a viable alternative to surgery in many clinical scenarios. This article discusses both standard and advanced endoscopic approaches to capsule retention, and presents an algorithmic approach to their utilization.

Correlation between MRCP and ERCP findings at a tertiary care hospital.

BACKGROUND: It is common clinical practice to obtain Magnetic Resonance Cholangiopancreatography (MRCP) prior to Endoscopic Retrograde Cholangiopancreatography (ERCP) to evaluate the biliary system. With recent improvements of MRCP, it is important to correlate the findings of these two studies. AIM: To examine the correlation between MRCP and ERCP findings in patients at a tertiary care hospital. METHODS: A total of 165 patients were identified who underwent MRCP prior to ERCP at West Virginia University between July 1, 2004 and June 30, 2006 (98 females and 67 males). Patients' demographic information and their laboratory values and diagnostic study outcomes prior to procedure were collected, entered into MS Access, and analyzed using SAS 10.0. Sensitivity, specificity, positive predictive value and negative predictive value were calculated. Two-tailed p-values of <= 0.05 were considered statistically significant. RESULTS: Baseline demographic characteristics were comparable between male and female patients. Hepatobiliary and pancreatic duct results were grouped together. MRCP was 74.6% sensitive and 83.5% specific for choledocholithiasis, 85.4% sensitive and 87.4% specific for strictures, 85.9% sensitive and 91.2% specific for obstruction, 92.4% sensitive and 93.5% specific for ductal dilatation, and 90.8% sensitive and 92.6% specific for detection of periductal masses. MRCP appeared to have more false negative results for choledocholithiasis and strictures and more false positive results for ductal dilatation and periductal mass detection compared with ERCP. CONCLUSIONS: In patients with presentations suggestive of hepatobiliary and pancreatic disease, despite recent improvements in MRCP technique, the sensitivity and specificity of MRCP is still not close enough to that of ERCP for detection of choledocholithiasis, hepatobiliary and pancreatic ductal dilatation, periductal masses, or obstruction to be used as a substitute. Thus, ERCP remains the gold standard for visualization of the hepatobiliary and pancreatic tree.

Utility of upper endoscopy and colonoscopy in evaluating gastrointestinal luminal wall thickening found on computed tomography.

BACKGROUND: Abdominal computed tomography (CT) scans are frequently performed for a variety of abdominal complaints. Not infrequently, bowel wall thickening noted on these radiographic studies of the gastrointestinal (GI) tract prompt further endoscopic evaluation. It is unclear whether the costs and risks of endoscopy are justified given the subsequent yield on endoscopic examination of this radiological finding. MATERIALS AND METHODS: A retrospective study was done on patients referred to the Digestive Diseases section of a tertiary level hospital for abnormal findings seen on CT during the study period. These patients were seen over one year and their charts reviewed. The items reviewed in the charts were: age, gender, chief complaint, physical findings, ordering location, CT scan indication, CT scan abnormality, endoscopic findings, and the time interval between CT scan and endoscopic procedure. RESULTS: A total of 169 patients with bowel wall thickening that proceeded to an endoscopy were identified. The average age for the patients was 18 to 89 with a mean of 55 years. Females comprised 59% of the patients. The mean period from the time of the CT scan to endoscopy was 32 days. In the upper GI tract, 39 patients had bowel wall thickening. Of these, 25 had abnormal pathology on subsequent endoscopy correlating with the radiological findings. In the lower GI tract, 109 patients had bowel wall thickening. Of these, 36 had abnormal findings on the subsequent endoscopy. In this group, 10% was found to be of neoplastic origin upon further work-up. The positive predictive value (PPV) for bowel wall thickening in the UGI tract was 64%. In the lower GI tract, the PPV was 33%. CONCLUSION: Thickening of the gastrointestinal tract is not uncommonly noted on abdominal CT scans. The resultant endoscopic evaluations of these findings appear to yield more when these changes are seen in the upper GI tract as compared to the lower GI tract. Luminal wall thickening in the upper GI tract seen on CT is a very useful predictor of pathology (PPV = 64%). For colonic wall thickening seen on CT, the PPV was only 33%. Nevertheless, we recommend direct visualization as 10% of these findings were found to be malignancies on follow-up.

Overexpression of epidermal growth factor and hepatocyte growth factor receptors in a proportion of gastrinomas correlates with aggressive growth and lower curability.

PURPOSE: Growth factor receptor expression and activation, particularly for epidermal growth factor (EGF) and hepatocyte growth factor (HGF), in many endocrine and nonendocrine tumors is important in determining tumor recurrence, growth, and aggressiveness. Whether this is true of neuroendocrine tumors such as gastrinomas is unclear. EXPERIMENTAL DESIGN: To address this question, we analyzed the extent of EGFR and HGFR expression in gastrinomas from 38 patients with Zollinger-Ellison syndrome and correlated it with clinical and tumor characteristics. EGFR (n = 38) and HGFR (n = 22) mRNA levels were determined by competitive PCR, and immunohistochemistry was performed on a subset. RESULTS: In each of the gastrinomas studied, detectable levels of EGFR and HGFR mRNA were present. Low levels of EGFR protein expression were detected in 40% of gastrinomas and HGFR protein expression in 90%. EGFR mRNA expression varied by 1050-fold and HGFR by 375-fold. Eighteen percent of gastrinomas overexpressed EGFR mRNA and 14% overexpressed HGFR mRNA, compared with normal pancreas. Maximal EGFR and HGFR mRNA levels were 4- and 1.2-fold increased and correlated with the presence of liver metastases (P = 0.034) and decreased long-term curability (P = 0.027) but not tumor location, size, or tumor functional characteristics. CONCLUSIONS: These above results indicate that EGFR and HGFR mRNA are universally expressed in gastrinomas. Furthermore, each is overexpressed in a minority (15-20%) of the gastrinomas, and the overexpression correlates with aggressive growth and lower curability.

Her-2/neu expression and gene amplification in gastrinomas: correlations with tumor biology, growth, and aggressiveness.

A proportion of gastrointestinal neuroendocrine tumors are aggressive; however, little is known of molecular determinants of their growth, and molecular studies have identified no useful prognostic factors. Overexpression of HER-2/neu is common in some nonendocrine tumors, frequently correlates with increased tumor aggressiveness, and can be used as a basis of treatment with trastuzumab. Little is known of its expression in malignant pancreatic endocrine tumors. In the present study HER-2/neu gene amplification and expression was determined in 43 gastrinomas from different patients. Results were correlated with clinical, laboratory, and tumor characteristics including tumor growth. HER-2/neu gene amplification was assessed by differential PCR, mRNA levels assessed by quantitative PCR, and protein by immunohistochemistry. Fourteen percent of patients had HER-2/neu gene amplification in tumors compared with levels in their WBCs. HER-2/neu mRNA varied over a 700-fold range. However, only 3% exceeded levels seen in normal pancreas, and immunohistochemistry did not show protein overexpression in any tumor (n = 10). HER-2/neu mRNA levels were significantly higher (P = 0.032) in tumors associated with liver metastases but not with tumor location or size. These results show that HER-2/neu amplification/overexpression does not seem to play a role in the molecular pathogenesis of most gastrinomas, as suggested in a previous study involving small numbers of cases. However, mild gene amplification occurs in a subset, and overexpression is associated with aggressiveness. Therefore, HER-2/neu levels could have prognostic significance as well as identify a patient subset with gastrinomas who might benefit from trastuzumab treatment.