Pancreatic Cancer Screening for At-Risk Individuals (Pancreas Scan Study): Yield, Harms, and Outcomes From a Prospective Multicenter Study.

INTRODUCTION: Guidelines endorse pancreatic cancer screening in genetically susceptible individuals. We conducted a prospective, multicenter study to determine yield, harms, and outcomes of pancreatic cancer screening. METHODS: All high-risk individuals undergoing pancreatic cancer screening at 5 centers from 2020 to 2022 were prospectively enrolled. Pancreas findings were designated as low-risk (fatty or chronic pancreatitis-like changes), intermediate-risk (neuroendocrine tumor [NET] <2 cm or branch-duct intraductal papillary mucinous neoplasm [IPMN]), or high-risk lesions (high-grade pancreatic intraepithelial neoplasia/dysplasia, main-duct IPMN, NET >2 cm, or pancreatic cancer). Harms from screening included adverse events during screening or undergoing low-yield pancreatic surgery. Annual screening was performed using endoscopic ultrasound and or magnetic resonance cholangiopancreatography. Annual screening for new-onset diabetes using fasting blood sugar was also performed ( ClinicalTrials.gov : NCT05006131). RESULTS: During the study period, 252 patients underwent pancreatic cancer screening. Mean age was 59.9 years, 69% were female, and 79.4% were White. Common indications were BRCA 1/2 (36.9%), familial pancreatic cancer syndrome kindred (31.7%), ataxia telangiectasia mutated (3.5%), Lynch syndrome (6.7%), Peutz-Jeghers (4.3%), and familial atypical multiple mole melanoma (3.5%). Low-risk lesions were noted in 23.4% and intermediate-risk lesions in 31.7%, almost all of which were branch-duct IPMN without worrisome features. High-risk lesions were noted in 2 patients (0.8%), who were diagnosed with pancreas cancer at stages T2N1M0 and T2N1M1. Prediabetes was noted in 18.2% and new-onset diabetes in 1.7%. Abnormal fasting blood sugar was not associated with pancreatic lesions. There were no adverse events from screening tests, and no patient underwent low-yield pancreatic surgery. DISCUSSION: Pancreatic cancer screening detected high-risk lesions with lower frequency than previously reported. No harms from screening were noted.

Incidence and Prevalence of Intraductal Papillary Mucinous Neoplasms in Individuals With BRCA1 and BRCA2 Pathogenic Variant.

BACKGROUND: The natural history of branch-duct intraductal papillary neoplasm (BD-IPMN) in BRCA1/2 patients is unknown. Our goal was to estimate the incidence and prevalence of BD-IPMN and other pancreatic lesions in BRCA1/2 patients and compare it to that for average-risk individuals. METHODS: We identified a cohort of BRCA1/2 patients followed at our institution between 1995 and 2020. Medical records and imaging results were reviewed to determine prevalence of pancreatic lesions. We then identified those who had undergone follow-up imaging and determined the incidence of new pancreatic lesions. We categorized pancreatic lesions as low, intermediate, or high-risk based on their malignant potential. RESULTS: During the study period, 359 eligible BRCA1/2 patients were identified. Average patient age was 56.8 years, 88.3% were women, and 51.5% had BRCA1 . The prevalence of low-risk pancreatic lesions was 14.4%, intermediate-risk 13.9%, and high-risk 3.3%. The prevalence of BD-IPMN was 13.6% with mean cyst size 7.7 mm (range: 2 to 34 mm). The prevalence of pancreatic cancer was 3.1%. Subsequent imaging was performed in 169 patents with mean follow-up interval of 5.3 years (range: 0 to 19.7 y). The incidence of BD-IPMN was 20.1%, with median cyst size 5.5 mm (range: 2 to 30 mm). The incidence of pancreatic cancer was 2.9%. BRCA2 patients were almost 4-times more likely to develop pancreatic cancer than BRCA1 patients, however, there was no difference in incidence or prevalence of BD-IPMN. CONCLUSIONS: Incidence and prevalence of BD-IPMNs in BRCA1/2 patients was similar to that reported for average-risk individuals. BRCA2 patients were more likely than BRCA1 patients to develop pancreatic cancer but had similar rates of BD-IPMN.

Association Between Family History and Risk of Pancreatic Cancer in Patients With BRCA1 and BRCA2 Pathogenic Variants.

OBJECTIVES: Current guidelines limit pancreatic cancer screening to those BRCA1/2 patients who have a family history of pancreatic cancer. We aimed to assess the association between family history and risk of pancreatic neoplasms in BRCA1/2 patients. METHODS: We reviewed medical records of BRCA1/2 patients followed at our institution between 1995 and 2020. Family history was defined as those with a first-degree relative with pancreatic cancer. We compared the incidence and prevalence of pancreatic neoplasms between patients with and without family history of pancreatic cancer. RESULTS: We identified 56 BRCA1/2 patients with family history and 238 without family history of pancreatic cancer. No difference between these groups was noted in age, race, or sex. Mean follow-up interval for BRCA1/2 patients was 4.6 years (range, 0-19.7 years). There was no significant difference in prevalence (19.6% vs 12.6; P = 0.3) or incidence (29% vs 14.1%; P = 0.08) of branch-duct intraductal papillary mucinous neoplasm between the 2 groups. No association between family history and pancreatic cancer risk was noted. Only 1 of 10 BRCA1/2 patients with pancreatic cancer had a family history. CONCLUSIONS: Our results do not support using family history to determine eligibility for pancreatic cancer screening.

Comparison of Assays for Therapeutic Monitoring of Infliximab and Adalimumab in Patients With Inflammatory Bowel Diseases.

Comparison data regarding anti-tumor necrosis factor drug concentrations in inflammatory bowel disease (IBD) between the enzyme-linked immunosorbent assay (ELISA) and the homogenous mobility shift assay (HMSA) are scarce.1-3 As decisions in clinical practice depend on the thresholds that define a therapeutic drug concentration, it is important to determine if this varies based on the type of assay used for therapeutic drug monitoring.4 We recently showed a discrepancy between a commercially available ELISA and the HMSA for both infliximab and adalimumab concentrations in patients with IBD.5 Based on the results of the study, Prometheus Laboratories (San Diego, CA) initiated a comprehensive review of their HMSA assays and found that there was an upward drift for both infliximab (from December 2017 to May 2019) and adalimumab (from August 2017 to May 2019), including when our study was performed. Prometheus Laboratories corrected the errant values and reported the revised drug concentrations to physicians (Supplementary Methods). We aimed to compare the corrected infliximab and adalimumab concentrations with the original ELISA values.

Clinical Impact of Corrections to Infliximab and Adalimumab Monitoring Results with the Homogeneous Mobility Shift Assay.

An upward drift for both infliximab and adalimumab concentrations measured by the homogenous mobility shift assay (HMSA) was previously reported. We aimed to investigate the impact of this drift on clinical care of patients with inflammatory bowel disease. This was a retrospective, multicenter study. Providers reviewed the individual patient data and drug concentrations before and after the laboratory corrections and then documented whether a different clinical decision would have been made had the corrected drug concentration been originally reported. A multivariable Cox proportional hazards regression analysis was performed to investigate the association of a documented treatment change with treatment failure, defined as drug discontinuation for primary nonresponse, loss of response, or serious adverse event, adjusting for confounding factors. The study population consisted of 479 patients (infliximab, n = 219; adalimumab, n = 260). Upon review, 14.9% (71/479) patients would have had a different treatment decision made had the corrected drug concentration been initially reported. After a median follow-up of 10.6 months, 25.7% of patients (123/479) had treatment failure. A theoretical different clinical decision based on the corrected drug concentrations was not associated with treatment failure (adjusted hazard ratio (HR): 1.452; 95% confidence interval (CI): 0.805-2.618; p = 0.216), which was consistent for both infliximab (adjusted HR: 1.977; 95% CI: 0.695-5.627; p = 0.201) and adalimumab (adjusted HR: 1.484; 95% CI: 0.721-3.054; p = 0.284). The drift in infliximab and adalimumab concentrations in the HMSA assay affected treatment decisions in 15% of cases. However, this discrepancy was not associated with a higher cumulative probability for treatment failure.

Advances in Hereditary Colorectal and Pancreatic Cancers.

PURPOSE: Innovations in genetic medicine have led to improvements in the early detection, prevention, and treatment of cancer for patients with inherited risks of gastrointestinal cancer, particularly hereditary colorectal cancer and hereditary pancreatic cancer. METHODS: This review provides an update on recent data and key advances that have improved the identification, understanding, and management of patients with hereditary colorectal cancer and hereditary pancreatic cancer. FINDINGS: This review details recent and emerging data that highlight the developing landscape of genetics in hereditary colorectal and pancreatic cancer risk. A summary is provided of the current state-of-the-art practices for identifying, evaluating, and managing patients with suspected hereditary colorectal cancer and pancreatic cancer risk. The impact of next-generation sequencing technologies in the clinical diagnosis of hereditary gastrointestinal cancer and also in discovery efforts of new genes linked to familial cancer risk are discussed. Emerging targeted therapies that may play a particularly important role in the treatment of patients with hereditary forms of colorectal cancer and pancreatic cancer are also reviewed. Current approaches for pancreatic cancer screening and the psychosocial impact of such procedures are also detailed. IMPLICATIONS: Given the availability of new diagnostic, risk-reducing, and therapeutic strategies that exist for patients with hereditary risk of colorectal or pancreatic cancer, it is imperative that clinicians be vigilant about evaluating patients for hereditary cancer syndromes. Continuing to advance genetics research in hereditary gastrointestinal cancers will allow for more progress to be made in personalized medicine and prevention.

Efficacy and safety of natalizumab in Crohn's disease patients treated at 6 Boston academic hospitals.

BACKGROUND: Despite trials demonstrating its efficacy, many physicians harbor concerns regarding the use of natalizumab in the treatment of patients with refractory Crohn's disease (CD). The purpose of this study was to perform a descriptive analysis of a series of CD patients not currently enrolled in a clinical trial. METHODS: A retrospective case review of patients treated with natalizumab at 6 sites in Massachusetts: Boston Medical Center, Beth Israel Deaconess Medical Center, Brigham & Women's Hospital, Lahey Clinic, Massachusetts General Hospital, and UMass Medical Center. RESULTS: Data on 69 CD patients on natalizumab were collected. At the start of treatment, patients' disease duration was 12 years. A high proportion of patients were women (68%), presented with perianal disease (65%) and upper gastrointestinal tract involvement (14%). Prior nonbiologic therapies were steroids (96%), thiopurines (94%), antibiotics (74%), methotrexate (58%), and at least two anti-tumor necrosis factor agent failures (81%). Sixty-nine percent (44 of 64 patients) with available medical evaluation had a partial or complete clinical response. Loss of response was 13% after an average of 1 year of treatment. Adverse events were infusion reactions, headaches, fever, and infections. No case of progressive multifocal leukoencephalopathy was observed. CONCLUSIONS: In our clinical experience outside the context of a clinical trial, natalizumab is largely reserved for CD patients with extensive ileocolonic disease who have failed conventional immunosuppressants and of at least 2 anti-tumor necrosis factor agents. This drug is, however, well tolerated and offers significant clinical improvement for more than a year in one-third of these difficult-to-treat CD patients.

Development of quality measures for monitoring and improving care in gastroenterology.

Over the past decade, most quality assurance (QA) efforts in gastroenterology have been aimed at endoscopy. Endoscopic quality improvement was the rational area to begin QA work in gastroenterology due to the relatively acute nature of complications and the high volume of procedures performed. While endoscopy is currently the focus of most quality assurance (QA) measures in gastroenterology, more recent efforts have begun to address clinical gastroenterology practices both in the outpatient and inpatient settings. Clinical outpatient and inpatient gastroenterology is laden with areas where standardization could benefit patient care. While data and experience in clinical gastroenterology QA is relatively limited, it is clear that inconsistent use of guidelines and practice variations in gastroenterology can lead to lower quality care. In this review, we review a variety of areas in clinical gastroenterology where existing guidelines and published data suggest both the need and practicality of active QA measures.