The Pancreatic Cancer Early Detection (PRECEDE) Study is a Global Effort to Drive Early Detection: Baseline Imaging Findings in High-Risk Individuals.

BACKGROUND: Pancreatic adenocarcinoma (PC) is a highly lethal malignancy with a survival rate of only 12%. Surveillance is recommended for high-risk individuals (HRIs), but it is not widely adopted. To address this unmet clinical need and drive early diagnosis research, we established the Pancreatic Cancer Early Detection (PRECEDE) Consortium. METHODS: PRECEDE is a multi-institutional international collaboration that has undertaken an observational prospective cohort study. Individuals (aged 18-90 years) are enrolled into 1 of 7 cohorts based on family history and pathogenic germline variant (PGV) status. From April 1, 2020, to November 21, 2022, a total of 3,402 participants were enrolled in 1 of 7 study cohorts, with 1,759 (51.7%) meeting criteria for the highest-risk cohort (Cohort 1). Cohort 1 HRIs underwent germline testing and pancreas imaging by MRI/MR-cholangiopancreatography or endoscopic ultrasound. RESULTS: A total of 1,400 participants in Cohort 1 (79.6%) had completed baseline imaging and were subclassified into 3 groups based on familial PC (FPC; n=670), a PGV and FPC (PGV+/FPC+; n=115), and a PGV with a pedigree that does not meet FPC criteria (PGV+/FPC-; n=615). One HRI was diagnosed with stage IIB PC on study entry, and 35.1% of HRIs harbored pancreatic cysts. Increasing age (odds ratio, 1.05; P<.001) and FPC group assignment (odds ratio, 1.57; P<.001; relative to PGV+/FPC-) were independent predictors of harboring a pancreatic cyst. CONCLUSIONS: PRECEDE provides infrastructure support to increase access to clinical surveillance for HRIs worldwide, while aiming to drive early PC detection advancements through longitudinal standardized clinical data, imaging, and biospecimen captures. Increased cyst prevalence in HRIs with FPC suggests that FPC may infer distinct biological processes. To enable the development of PC surveillance approaches better tailored to risk category, we recommend adoption of subclassification of HRIs into FPC, PGV+/FPC+, and PGV+/FPC- risk groups by surveillance protocols.

See Something, Say Something: Global Positioning System Tracker Foreign Body Ingestion as a Unique Presentation of Human Trafficking.

In 2021, there were about 17,000 victims of human trafficking in the United States. We present a case of a 28-year-old sex trafficking victim who was forced to swallow 2 global positioning system trackers by her perpetrator. The gastroenterology team performed an upper endoscopy and retrieved 2 global positioning system devices from her antrum. Most of these victims do not disclose any history of abuse because of fear of their perpetrators. Further training and research can help to allow for recognition of these victims and potentially help them.

Demographics, distance to gastrointestinal specialists, and social deprivation are associated with advanced stage of gastrointestinal cancer diagnosis.

Background: Gastrointestinal (GI) luminal cancers can be detected at early stages by endoscopic procedures. Place-based factors, such as social deprivation and distance to specialist care, are under-investigated with regard to the stage of diagnosis. Methods: This was a retrospective cohort study among persons ≥18 years of age in the Florida Cancer Data System, a population-based cancer incidence registry. We included persons diagnosed with esophageal cancer, gastric canceror colorectal cancer, with at least 1 measure of geographic location during the period January 1, 1981, to December 31, 2016. Multivariate multinomial logistic regression was used to identify factors associated with the stage of diagnosis, including social deprivation and proximity to GI care. Results: Among 379,054 persons, the median age was 71 years, and 54% were male. Distant stage disease was significantly less likely than local stage in those of non-Hispanic/Latino ethnicity (odds ratio [OR] 0.92, 95% confidence interval [CI] 0.89-0.94, P<0.001). Distant disease was more likely in African Americans (OR 1.30, 95%CI 1.26-1.34) and Asians (OR 1.41, 95%CI 1.27-1.56, P<0.001), with each 5-min increase in travel time to specialists, (OR 1.02, 95%CI 1.01-1.02, P<0.001), and with each 10-point increase in Social Deprivation Index (OR 1.01, 95%CI 1.01-1.02, P<0.001). Conclusions: A greater distance from care and living in areas with increased deprivation are associated with an advanced stage of diagnosis and should be recipients of policy-driven efforts to improve access to care. That the strongest risk factors include minority race and ethnicity underlines the complexity of healthcare disparities.

Triple Primary Cancers: An Analysis of Genetic and Environmental Factors.

The occurrence of multiple primary cancers (MPC) is thought to reflect increased cancer susceptibility in patients due to a combination of genetic and environmental factors. Here we conducted a retrospective review of 2,894 consecutive patients evaluated at a single institution and identified 31 (1.14%) individuals with a history of three or more primary cancers, then analyzed the genetic and environmental influences associated with their propensity for developing malignancies. We found that 35.5% of patients had a hereditary cancer syndrome (HCS), with high penetrance HCS in 72.7% of cases, suggesting that monogenic causes underly a significant proportion of triple primary cancer risk. Analysis of cancer frequencies found that the diagnosis of breast cancer was associated with a significantly lower likelihood of HCS, while the diagnosis of colorectal, prostate, and pancreas cancer was associated with a significantly higher likelihood of HCS. Comparison of HCS-positive and HCS-negative patients revealed similar demographic characteristics, mean age at first diagnosis, and family history of cancer. Moreover, no significant differences in lifestyle behaviors, occupational exposures, chronic health conditions, or treatment with chemotherapy and radiation were observed between HCS-positive and -negative groups, though outliers in tobacco smoking, as well as systemic treatment after both first and second primary cancers were observed. These findings indicate a robust contribution of HCS to cancer susceptibility among patients with triple primary cancers while environmental influences were less evident. This emphasizes the need for larger MPC cohorts incorporating additional genetic and environmental factors to more comprehensively characterize drivers of cancer risk. PREVENTION RELEVANCE: In patients with three or more primary cancers, genetic predisposition explained a significant proportion of cases; however, treatment history, lifestyle habits, and other exposures appeared to play a less significant role. This highlights the value of early genetic screening and the need to develop more sensitive markers of cancer susceptibility. See related Spotlight, p. 193.

Racial, Ethnic, and Sex-based Disparities among High-risk Individuals Undergoing Pancreatic Cancer Surveillance.

Since its inception two years ago, the international, multicenter Pancreatic Cancer Early Detection (PRECEDE) Consortium has enrolled high-risk individuals (HRI) undergoing pancreatic ductal adenocarcinoma (PDAC) surveillance. Herein we aim to evaluate enrollment disparities in PRECEDE. Data on HRIs enrolled between May 2020 and March 2022 were collected, with HRIs defined as participants enrolled in PRECEDE meeting guideline-based criteria for PDAC surveillance. Of 1,273 HRIs enrolled, 1,113 were eligible for inclusion, with 47.2% meeting familial pancreatic cancer criteria without a known pathogenic variant (PV) and the remainder having a pathogenic variant in a PDAC-risk gene (CDKN2A, STK11, PRSS1, BRCA1, BRCA2, PALB2, ATM, MLH1, MSH2, MSH6, PMS2, or EPCAM). Study participants were predominantly from the United States (82.7%), the most common age range at enrollment was 60-69 years (37.4%), and a non-PDAC cancer was present in 32.4%. There were racial/ethnic- and sex-based disparities among enrolled subjects, as the majority of participants were female (65.9%) and self-reported white (87.7%), with only 2.9% having Hispanic ethnicity. While more than 97% of participants consented to utilize imaging data and biosamples for research, there was no difference in rate of consent based on race/ethnicity, sex, or age, thereby demonstrating uniform participation in research activities among all subgroups after enrollment. Ensuring that diversity of HRIs in PDAC surveillance programs mirrors the communities served by participating centers is important. Substantial racial/ethnic- and sex-based disparities persist among recently enrolled HRIs undergoing PDAC surveillance, and therefore reducing these disparities will be a major focus of the PRECEDE Consortium moving forward. PREVENTION RELEVANCE: Pancreatic cancer surveillance is critical to decreasing pancreatic cancer mortality; therefore, it is important that pancreatic cancer surveillance studies enroll diverse patients. We demonstrate that substantial racial/ethnic- and sex-based disparities exist amongst enrollment in the international PRECEDE consortium, highlighting the dire need for future efforts to reduce these disparities. See related Spotlight, p. 305.

Two unique BAP1 pathogenic variants identified in the same family by panel cascade testing.

Germline pathogenic variants in the tumor suppressor gene BAP1 are associated with the hereditary tumor predisposition syndrome with susceptibility to uveal melanoma, mesothelioma, cutaneous melanoma, renal cell carcinoma, and other cancers. Germline BAP1 pathogenic variants are rare in the non-cancer general population with an estimated carrier frequency of 1:19,898 but more common in cancer patients with a carrier frequency of 1:1299. In the following we present the first report of a family with two unique BAP1 pathogenic variants. Retrospective case report of a family with two unique pathogenic variants in BAP1. A male (proband) was referred to our ocular oncology clinic for second opinion for his multiple independent uveal melanomas at ages 65, 68 and 71. Given his personal history of squamous cell carcinoma at age 61, renal cell carcinoma at age 63, and family history of atypical meningioma, basal cell carcinoma, pancreatic and prostate cancers he was assessed for germline pathogenic variants in BAP1 through our ongoing research study. Sanger sequencing identified the American founder pathogenic variant, c.1717delC, pL573Wfs*3, that was confirmed in a clinical laboratory. Both the proband's brother and nephew tested negative for the familial variant through single site cascade genetic testing. However, based on the personal history of multiple basal cell carcinoma in the nephew and family history of pancreatic and laryngeal cancers (both not known to be associated with BAP1-TPDS), a large cancer panel testing was recommended for the nephew. His panel testing revealed a different BAP1 pathogenic variant, c.605G>A, p. Trp202*. This variant was not detected in the proband or the proband's brother. Based on the frequency of germline BAP1 variants in the cancer population, the chance of occurrence of two different BAP1 variants in a family with cancer history is 5.9 × 10-7. This case report provides support for the importance of offering large panel cascade genetic testing, rather than single site testing for only the family pathogenic variant, for all at risk family members especially when the family variant cannot explain all the cancers in the family.

Outcomes of upper endoscopy screening in Lynch syndrome: a meta-analysis.

BACKGROUND AND AIMS: Lynch syndrome (LS) predisposes affected individuals to a high lifetime risk of malignancies, including colorectal, endometrial, gastric, and duodenal cancers. The role of upper GI (UGI) cancer screening in LS has been uncertain, but recent studies have evaluated its utility. METHODS: Databases were queried through December 2021 to identify studies that examined upper endoscopy screening in LS using EGD. Mantel-Haenszel pooled odds ratios and 95% confidence intervals (CIs) for outcomes were constructed using a random-effects model to identify pooled odds of endoscopic findings in persons with LS. Event rates for detection of gastric and duodenal cancers, high-risk lesions, and clinically actionable findings were calculated. Statistical heterogeneity was assessed using the I2 statistic. RESULTS: Nine studies were identified with 2356 LS patients undergoing approximately 7838 EGDs. In total, 47 LS-associated UGI cancers (18 gastric and 29 duodenal cancers), 237 high-risk lesions, and 335 clinically actionable findings were identified. The pooled event rate for detection of any UGI cancer, high-risk lesions, and clinically actionable findings during screening were .9% (95% CI, .3-2.1; I2 = 89%), 4.2% (95% CI, 1.6-10.9; I2 = 98%), and 6.2% (95% CI, 2.2-16.5; I2 = 99%), respectively. There was no difference between LS-associated gene and gastric or duodenal cancer detection. CONCLUSIONS: In LS, there is evidence that endoscopic screening detects UGI cancers, precancerous lesions, and other clinically actionable findings that favor its use as a part of cancer risk management in LS.

Combining Pentoxifylline With Vedolizumab for Crohn's Disease: Results of a Randomised, Placebo-controlled Pilot Study.

BACKGROUND AND AIMS: The efficacy of current biologics may be limited by targeting only one pathway. Pentoxifylline [PTX] interferes with tumour necrosis factor [TNF] gene expression. We performed a randomised, placebo-controlled pilot study to determine if PTX plus vedolizumab [VDZ] in patients with Crohn's disease [CD] is safe and improves response compared with VDZ monotherapy. METHODS: Thirty adult patients with active CD were randomised to VDZ/PTX or VDZ/placebo and followed for 24 weeks. Endoscopic activity and inflammatory cytokines were measured at baseline and Week 24. Descriptive statistics were used to determine estimates of effect. RESULTS: Demographics were similar but baseline disease activity was higher in the VDZ/PTX group. There was no difference in clinical remission at Week 14 (60.0% vs 66.67%, odds ratio [OR] 0.76, 95% confidence interval [CI] 0.16, 3.51) or steroid-free clinical remission at Week 24 in patients receiving VDZ/PTX. Improved clinical response was noted in the VDZ/PTX group at Weeks 6, 14, and 24 [Week 6: 20% vs 6.67%, Week 14: 26.67% vs 6.67%, Week 24: 40% vs 20%]. The rate of endoscopic remission was similar between the groups [40% vs 33.33%], with a greater mean decrease in Simple Endoscopic Score-CD [SES-CD] and C-reactive protein [CRP] with VDZ/PTX [SES-CD -3.17 vs -0.15, CRP -5.56 vs 0.46]. An increase in serum TNF-α concentration was observed with VDZ/placebo group; PTX mitigated this effect. No serious adverse events occurred. CONCLUSIONS: VDZ/PTX did not provide benefit over VDZ monotherapy in clinical or endoscopic remission but appeared to improve clinical response and was safe. These data should inform a fully powered study.

Factors Associated With Geographic Disparities in Gastrointestinal Cancer Mortality in the United States.

BACKGROUND & AIMS: Significant geographic variability in gastrointestinal (GI) cancer-related death has been reported in the United States. We aimed to evaluate both modifiable and nonmodifiable factors associated with intercounty differences in mortality due to GI cancer. METHODS: Data from the Centers for Disease Control and Prevention's Wide-ranging Online Data for Epidemiologic Research platform were used to calculate county-level mortality from esophageal, gastric, pancreatic, and colorectal cancers. Multivariable linear regression models were fit to adjust for county-level covariables, considering both patient (eg, sex, race, obesity, diabetes, alcohol, and smoking) and structural factors (eg, specialist density, poverty, insurance prevalence, and colon cancer screening prevalence). Intercounty variability in GI cancer-related mortality explained by these covariables was expressed as the multivariable model R2. RESULTS: There were significant geographic disparities in GI cancer-related county-level mortality across the US from 2010-2019 with the ratio of mortality between 90th and 10th percentile counties ranging from 1.5 (pancreatic) to 2.1 (gastric cancer). Counties with the highest 5% mortality rates for gastric, pancreatic, and colorectal cancer were primarily in the Southeastern United States. Multivariable models explained 43%, 61%, 14%, and 39% of the intercounty variability in mortality rates for esophageal, gastric, pancreatic, and colorectal cancer, respectively. Cigarette smoking and rural residence (independent of specialist density) were most strongly associated with GI cancer-related mortality. CONCLUSIONS: Both patient and structural factors contribute to significant geographic differences in mortality from GI cancers. Our findings support continued public health efforts to reduce smoking use and improve care for rural patients, which may contribute to a reduction in disparities in GI cancer-related death.

Association Between Immunosuppressive Therapy and Outcome of Clostridioides difficile Infection: Systematic Review and Meta-Analysis.

BACKGROUND: Patients with Clostridioides difficile infection (CDI) often have coexisting medical problems requiring immunosuppressive therapy. However, limited data are available on the association between immunosuppressive therapy and CDI outcomes. AIM: To determine the association between immunosuppressive therapy and CDI outcomes. METHODS: PubMed, Embase, and Cochrane Library were searched through February 2021. Two reviewers independently reviewed and included studies that compared adult CDI patients who received immunosuppressive therapy to those who did not. The primary outcome was complicated CDl, including death, surgery, shock, or ICU admission. Raw data or unadjusted odds ratios (ORs) were used to calculate pooled ORs with 95% confidence intervals (CIs). RESULTS: Twenty-two studies with a total of 5759 CDI patients were selected. Immunosuppressive therapy was significantly associated with both primary outcome and death, with pooled ORs of 1.61 (95% CI 1.33-1.96) and 1.73 (95% CI 1.39-2.15) separately. The association between corticosteroids and primary outcome was also significant with OR of 1.73 (95% CI 1.41, 2.12). In subgroup analysis, the factors explaining differences in study results included study quality, patient age, and whether individual studies had adjusted for potential confounders. In a systematic review, most studies suggested a positive association between immunosuppressive therapy and complicated outcomes of CDI in patients comorbid for IBD. CONCLUSIONS: Our systematic review and meta-analysis demonstrate that immunosuppressive therapy is a risk factor for complicated outcomes of CDI.

Marginal zone lymphoma of the colon: case series from a single center and SEER data review.

Colon extranodal marginal zone lymphoma (EMZL) is poorly characterized in the literature. We performed a retrospective review of patients with colon EMZL at our institution and from the Surveillance Epidemiology and End Results (SEER) database. Eight patients were identified in our institution with majority (88%) presenting with stage-I disease. Initial management included active surveillance, polypectomy followed by surveillance, and surgical resection followed by chemotherapy. One patient with concurrent prostate carcinoma received radiation to the rectum. Initial therapy led to complete remission in five out of six treated patients with four of them maintaining remission at 88 months. SEER database identified 361 patients with stage-I colon EMZL. Overall survival for this cohort was 73.9% at 10 years with no significant difference in outcomes between treatment groups. Our single institution experience and the SEER data analysis emphasize indolent nature of colon EMZL and need for non-aggressive therapeutic approaches.

Increasing uptake of colon cancer screening in a medically underserved population with the addition of blood-based testing.

BACKGROUND: Adherence to colorectal cancer screening in the United States is suboptimal, particularly in medically underserved populations due to significant barriers to care. Unique accessible, low-cost, and non-invasive screening tests for this population could greatly benefit current rates. In this article, we assess patient preference and the impact of offering a blood-based test on screening rates in a cost-free health fair setting from April 2017 to April 2019. METHODS: Participants who met colorectal cancer screening eligibility criteria set forth by the United States Preventive Services Task Force were recommended to attend the colon cancer screening station. Those participants who elected to attend were offered various, accepted screening methods, and if they declined, were offered alternative blood-based testing. Screening rates, test outcomes, and the rate of follow up completion of colonoscopy were measured and compared with historic screening outcomes. RESULTS: Of 1401 participants who were recommended to attend, 640 (45.7%) participants were evaluated at the colon cancer screening station, of whom 460 were eligible for testing. Amongst these, none selected colonoscopy, 30 (6.5%) selected fecal immunochemical testing, and 430 (93.5%) selected blood-based testing. Only 2 participants returned the fecal immunochemical tests. In the blood test cohort, 88 were positive and 20 received a follow up colonoscopy. CONCLUSIONS: Based on this assessment, blood-based testing is an effective method to increase screening rates in medically underserved populations, though efforts to further improve access to follow up colonoscopy are necessary.

Impact of the COVID-19 Pandemic on Clinical Schedules and Physical and Mental Well-Being of Gastroenterology Nonphysician Healthcare Workers: A Nationwide Survey.

COVID-19 was declared a pandemic in March 2020 by the World Health Organization. To minimize exposure and because of limited personal protective equipment resources, most gastroenterology practices were curtailed/modified during the surge, with slow reopening to a normal/semi-normal schedule. Gastroenterology healthcare workers have been impacted greatly by COVID-19, resulting in job and wage insecurity. The aim of our study was to understand the impact of COVID-19 on gastroenterology healthcare workers across the United States. A web-based survey, consisting of 40 questions, was disseminated among gastroenterology practices across the United States via en masse e-mails and direct contact by authors. In total, 223 gastroenterology healthcare workers completed the survey; 56.1% were from academic settings. COVID-19 impacted the work schedule of 85.2% of participants, with reduced weekly work hours (38.1%), duty reassignment (22.4%), and furlough (13.9%). Uncertainty about job and/or future wages/benefits after reopening was noted in 41%, which was significantly associated with the presence of physical (p = .021) and mental/emotional symptoms (p = .045). Worsening of pre-existing physical and/or mental/emotional conditions was observed in 53%. Inadequate personal protective equipment availability, lack of temporary housing and/or childcare facilities, as well as job insecurity appear to be the important factors leading to worsening physical/mental/emotional conditions among gastroenterology healthcare workers.

Disadvantages for non-Hispanic whites in gastric carcinoma survival in Florida.

PURPOSE: The prognosis for gastric carcinoma (GC) remains challenging with less than 35% of patients surviving 5 years. GC survival varies greatly by anatomical site, cardia and non-cardia. However, these important differences have not been thoroughly studied in relation to the increasing diversity in US populations such as Florida. In this study we examined, for the first time, the effect of race-ethnicity on risk of death from GC controlling for potential risk factors separately for cardia and non-cardia GCs. METHODS: Data on GCs diagnosed in Florida from 2005-2016 were obtained from the statewide cancer registry. Age-standardized GC-specific 5-year survival was computed by anatomical site and race-ethnicity. In addition, a competing risk analysis was performed to assess prognostic factors and to estimate subdistribution hazard ratios of death from GC. RESULTS: Whites had high proportions of cardia GC (43.9%) compared to all racial/ethnic minorities (10.9%, 19.6%, and 13.8% in Blacks, Hispanics, and Asians, respectively; p < .0001). Among 12,302 cases included, there were 7534 deaths from GC and 1179 from other causes. Age standardized GC-specific 5-year survival was significantly lower for Whites (28.0%) compared to Blacks (31.6%), Hispanics (37.6%), and Asians, (39.6%) and significantly lower for cardia GC (25.0%, 95% CI 23.4-26.6) compared to non-cardia GC (37.0%, 95% CI 35.5-38.4). Multivariable competing risk analysis in patients with non-cardia GC showed that Asians (sHR: 0.64, 95% CI 0.51-0.80), Hispanics (sHR 0.71, 95% CI 0.64-0.78), and Blacks (sHR 0.83, 95% CI 0.75-0.92) all had lower risks of death from GC compared to Whites. In patients with cardia GC, only Hispanics had statistically significant lower risk of death from GC than Whites (sHR 0.84, 95% CI 0.74-0.95, p = 0.005). CONCLUSIONS: The study of racial/ethnic survival disparities in patients with GC in Florida reveals Whites as the most disadvantaged group. Whites are more afflicted by cardia GC, which is associated with higher risk of death than non-cardia GC. However, even within non-cardia GC, Whites had higher risk of death than the other racial-ethnic groups. Commonly assessed survival determinants do not adequately explain these unusual disparities; thus, further investigation is warranted.

The Fallacy of Teaching and the Illusion of Learning: Improving Articulation of Basic Science in the Medical School Curriculum.

Despite calls from educators to re-engineer how faculty deliver medical student curricula with integrated basic science concepts, this content is still frequently disarticulated from other curricular components. We renewed our curriculum using evidence-based pedagogical and cognitive learning strategies to interleave basic science across the 4-year curriculum.