Pancreatic ductal adenocarcinoma is associated with a unique endocrinopathy distinct from type 2 diabetes mellitus.

INTRODUCTION: The majority of patients with pancreatic ductal adenocarcinoma (PC) display either impaired fasting glucose/glucose intolerance or overt diabetes. However, the pathophysiologic basis of this association remains largely unexplained. METHODS: In this case-control study we aimed to study the morphological changes in the islets of patients with PC, compared to control patients with and without type 2 diabetes mellitus (T2DM). T2DM controls and PC cases had a lower ß-cell area and average islet size and density compared to non-T2DM controls (p < 0.05). RESULTS: Compared to both T2DM and non-T2DM controls, mean α-cell area was significantly lower and ß/α-ratio was higher in PC cases (p < 0.05). Furthermore, whereas islets in T2DM controls were characterized by disrupted islet architecture and presence of islet amyloid aggregates, islet composition in PC islets was not significantly different compared to non-T2DM controls (p > 0.05 vs. Control). CONCLUSIONS: Our data shows that PC is associated with a unique pattern of islet pathology characterized by preserved architecture, absence of amyloid aggregates, and relative α-cell loss indicating that distinct mechanisms are likely involved in the pathophysiology of islet failure in PC-induced DM. Insights into the mechanisms mediating ß-cell failure in PC can be important for our understanding of pathophysiology of PC.

Epidemiology, Tumor Characteristics, and Survival in Patients With Primary Pancreatic Lymphoma: A Large Population-based Study Using the SEER Database.

INTRODUCTION: Primary pancreatic lymphoma (PPL) is an extranodal manifestation of non-Hodgkin lymphoma originating in the pancreas, which constitutes <1% of all pancreatic neoplasms. Because of the rarity of the disease, most data on PPL are derived from case reports and small case series. To provide better insight into the epidemiology, treatment, and outcomes of these patients, we conducted an analysis of patients with PPL from the Surveillance, Epidemiology and End Results (SEER) database, which is presented in this study. METHODS: Patients with PPL were identified using the International Classification of Disease for Oncology, third edition histology codes for lymphoma (9590/3-9734/3), with pancreas (C25.0-C25.9) listed as the primary disease site. We collected data on patient demographics, year of diagnosis, primary tumor site, histology, first line of treatment received, and survival until death or last follow-up for the period 1973-2014. RESULTS: Overall, 835 patients were included. The median (range) age of the study population was 67 (2 to 98) years. The median (95% confidence interval) overall survival for the cohort was 53 (37 to 73) months. On univariable analyses, age, stage, and use of chemotherapy were statistically associated with improved overall survival. Besides these factors, white race was associated with improved cause-specific survival on multivariable analysis. CONCLUSIONS: This large population-based series describes PPL in detail. Younger age, white race, early stage, and initial treatment with chemotherapy are associated with improved survival in patients with PPL.

Clinical spectrum of adult patients with annular pancreas: Findings from a large single institution cohort.

BACKGROUND AND AIMS: Annular pancreas (AnnP) is a rare congenital abnormality that results from the presence of a complete or partial ring of pancreatic tissue surrounding the descending portion of the duodenum. While the clinical presentation and management of AnnP in neonates and infants has been well described, the complete spectrum of clinical presentation of AP in adults is not very clear. We aimed to describe the clinical spectrum of presentation and management of adult patients with AnnP. METHODS: Using the electronic medical record, we identified 198 patients with radiologically and/or surgically confirmed AnnP evaluated at Mayo Clinic between 1995 and 2017. RESULTS: The mean age of the study population at diagnosis was 55.1 (±18.3) years (60% female). 60% of patients did not have symptoms attributable to pancreatic disease at the time of diagnosis and were diagnosed incidentally. Computed tomography (CT) was the most common modality (64%) of diagnosis. Among symptomatic patients, abdominal pain (50%), duodenal obstruction (31%) and acute pancreatitis (16%) were the most common symptoms (non-exclusive). While most patients with duodenal obstruction required surgery, all patients with acute pancreatitis could be managed conservatively in the absence of competing indications for intervention. CONCLUSION: AnnP may remain asymptomatic well into adulthood and be incidentally detected on abdominal imaging done for other indications. While surgery remains the mainstay of treatment in patients presenting with duodenal obstruction, a majority of these adult symptomatic patients with AnnP, including those with acute pancreatitis require no further treatment.

Autoimmune Pancreatitis.

Over the course of the last 2 decades our knowledge of autoimmune pancreatitis has increased exponentially. In this review, we summarize the clinical presentation, diagnosis and treatment of AIP, to better allow general gastroenterologists and primary care providers to consider AIP as a as a rare but important cause of painless obstructive jaundice and recurrent acute pancreatitis. While steroids remain the mainstay of first line therapy, a number of patients with type 1 AIP require immunomodulators or rituximab to maintain remission; recommendations on the management of relapses continue to evolve.

Comparison of Fasting Human Pancreatic Polypeptide Levels Among Patients With Pancreatic Ductal Adenocarcinoma, Chronic Pancreatitis, and Type 2 Diabetes Mellitus.

OBJECTIVES: Human pancreatic polypeptide (HPP) is a hormone secreted by the ventral pancreas. While postprandial HPP levels have been studied in chronic pancreatitis (CP) and pancreatic ductal adenocarcinoma (PDAC), there are limited data on fasting HPP in these diseases. METHODS: Fasting serum HPP was measured in the following groups of patients: CP with diabetes mellitus (DM) (n = 16), CP without DM (n = 34), PDAC with new-onset DM (n = 50), PDAC without DM (n = 49), new-onset type 2 DM (n = 50), and controls without DM (n = 49). Sixty-six had type 3c DM (CP with DM, n = 16; PDAC with new-onset DM, n = 50). RESULTS: Median fasting HPP levels (in picograms per milliliter) were similar among all groups. Median (interquartile range) HPP levels in new-onset type 2 DM (n = 50; 288.3 [80.1-1072.1]) were similar to those in type 3c DM (n = 66; 242.3 [64.9-890.9]) (P = 0.71). In PDAC (n = 99), HPP values were similar in pancreatic head (n = 75) versus body/tail (n = 24) tumors (245.3 [64.3-1091.3] vs 334.7 [136.1-841.5]; P = 0.95), regardless of DM. CONCLUSIONS: Fasting HPP levels are similar in CP, PDAC, and controls regardless of glycemic status.

Model to Determine Risk of Pancreatic Cancer in Patients With New-Onset Diabetes.

BACKGROUND & AIMS: Of patients with new-onset diabetes (NOD; based on glycemic status) older than 50 years, approximately 1% are diagnosed with pancreatic cancer (PC) within 3 years. We aimed to develop and validate a model to determine risk of PC in patients with NOD. METHODS: We retrospectively collected data from 4 independent and nonoverlapping cohorts of patients (N = 1,561) with NOD (based on glycemic status; data collected at date of diagnosis and 12 months previously) in the Rochester Epidemiology Project from January 1, 2000 through December 31, 2015 to create our model. The model weighed scores for 3 factors identified in the discovery cohort to be most strongly associated with PC (64 patients with PC and 192 with type 2 diabetes): change in weight, change in blood glucose, and age at onset of diabetes. We called our model Enriching New-Onset Diabetes for Pancreatic Cancer (ENDPAC). We validated the locked-down model and cutoff score in an independent population-based cohort of 1,096 patients with diabetes; of these, 9 patients (82%) had PC within 3 years of meeting the criteria for NOD. RESULTS: In the discovery cohort, the END-PAC model identified patients who developed PC within 3 years of diabetes onset (area under receiver operating characteristic curve 0.87); a score of at least 3 identified patients who developed PC with 80% sensitivity and specificity. In the validation cohort, a score of at least 3 identified 7 of 9 patients with PC (78%) with 85% specificity; the prevalence of PC in patients with a score of at least 3 (3.6%) was 4.4-fold greater than in patients with NOD. A high END-PAC score in patients who did not have PC (false positives) was often due to such factors as recent steroid use or different malignancy. An ENDPAC score no higher than 0 (in 49% of patients) meant that patients had an extremely low risk for PC. An END-PAC score of at least 3 identified 75% of patients in the discovery cohort more than 6 months before a diagnosis of PC. CONCLUSIONS: Based on change in weight, change in blood glucose, and age at onset of diabetes, we developed and validated a model to determine risk of PC in patients with NOD based on glycemic status (END-PAC model). An independent prospective study is needed to further validate this model, which could contribute to early detection of PC.

Metachronous colon polyps in younger versus older adults: a case-control study.

BACKGROUND AND AIMS: The incidence of colorectal cancer in the United States has decreased substantially in individuals aged 50 and older. In contrast, it is increasing in young adults. The polyp characteristics on baseline and follow-up colonoscopy in young adults are not well characterized. We describe the polyp characteristics on baseline and follow-up colonoscopy in adults <40 years and determined factors associated with the occurrence of metachronous, advanced neoplasia or high-risk (HR) polyp features. We compared the occurrence of metachronous advanced neoplasia in young adults with those 50 years and older to assess whether postpolypectomy surveillance guidelines seem appropriate for polyp-bearing adults less than age 40 years. METHODS: Patients <40 years of age with >1 polyp removed on colonoscopy followed by a postpolypectomy colonoscopy were eligible. The primary outcome was the occurrence of advanced neoplasia or HR polyp features on follow-up colonoscopy. Secondary endpoints included factors associated with metachronous advanced neoplasia in young adults. The occurrence of metachronous advanced neoplasia in young adults was compared with a cohort of patients aged 50 years and older. RESULTS: Included were 128 patients with a mean age of 34.9 years; 124 patients (97%) had adenomas and 7% had sessile serrated polyps (SSPs). Advanced neoplasia was seen in 35% of patients at baseline. The median follow-up time was 33.6 months. Metachronous advanced neoplasia was identified in 7% of patients on follow-up colonoscopy. Baseline factors associated with metachronous advanced neoplasia included the presence of an SSP (hazard ratio, 7.8; 95% CI, 1.09-56.3; P = .041) with a trend in those with advanced neoplasia (hazard ratio, 3.4; 95% confidence interval, .89-12.8; P = .072). The occurrence of metachronous advanced neoplasia did not differ between the young and older cohorts (7% vs 12.2%, P = .58); however, young adults were less likely to have HR polyp features on follow-up (8.6% vs 20.3%, P = .008). CONCLUSIONS: More than 1 in 3 adults <40 years old undergoing colonoscopy had advanced neoplasia on baseline colonoscopy. The occurrence of metachronous advanced neoplasia in young adults is similar to older adults and appears to be associated with the size, pathology, and number of baseline polyps. Our data suggest young polyp-bearing adults may undergo postpolypectomy colonoscopy at intervals currently recommended by national guidelines. Confirmation in larger studies is warranted.

Portal Hypertension Complications Are Frequently the First Presentation of NAFLD in Patients Undergoing Liver Transplantation Evaluation.

INTRODUCTION: Nonalcoholic fatty liver disease (NAFLD) is likely to replace Hepatitis C as the leading cause of cirrhosis resulting in liver transplantation (LT) within a few years. Unfortunately, due to the lack of established guidelines for the screening of NAFLD in high-risk populations, many patients present with portal hypertension complications as their first manifestation of NAFLD require a LT evaluation. We aimed to investigate what proportion of patients who underwent LT for NAFLD-cirrhosis had knowledge of their liver disease prior to presenting with portal hypertension complications and to identify differences in clinical parameters between those with and without knowledge of preexisting NAFLD. METHODS: Consecutive patients who underwent LT for NAFLD-cirrhosis at a tertiary referral center were included in the study. Demographic and clinical data at the time of the first LT evaluation visit were collected, and patient knowledge of previous NAFLD was documented. Ascites, variceal bleeding, hepatic encephalopathy, and thrombocytopenia leading to diagnosis of underlying cirrhosis were considered as the presenting symptoms of portal hypertension. A p < 0.05 was considered statistically significant. RESULTS: A total of 124 subjects who received LT for NAFLD-cirrhosis were included, 58 % (n = 72) were male. At the time of the first LT evaluation visit, 60 % had diabetes, the mean body mass index was 33.2 [28.6, 37.6] kg/m(2), and the mean Model for End-Stage Liver Disease (MELD) score was 14.0 [11.0, 19.0]. More importantly, 85/124 patients (68.5 %) had no knowledge of preexisting NAFLD prior to presentation with symptoms of portal hypertension. The presenting symptoms were new-onset ascites in 61 %, hepatic encephalopathy in 25 %, variceal bleeding in 18 %, thrombocytopenia in 9 %, and other in 9 % (non-exclusive). Patients with no prior knowledge of NAFLD were less likely to have a diagnosis of hypercholesterolemia (30 vs. 50 %, p = 0.035) and had a trend toward having higher MELD scores at the time of the first LT evaluation visit (15 vs. 13.5, p = 0.05) and presenting with encephalopathy (25 vs. 10 %, p = 0.06) compared to those with previous knowledge of NAFLD diagnosis. CONCLUSION: The majority of patients undergoing liver transplant evaluation for NAFLD-cirrhosis are not aware of underlying NAFLD until they present with features of portal hypertension. New guidelines should consider screening for NAFLD in certain high-risk groups as more effective treatments for NAFLD are emerging.

YouTube videos as a source of medical information during the Ebola hemorrhagic fever epidemic.

The content and quality of medical information available on video sharing websites such as YouTube is not known. We analyzed the source and quality of medical information about Ebola hemorrhagic fever (EHF) disseminated on YouTube and the video characteristics that influence viewer behavior. An inquiry for the search term 'Ebola' was made on YouTube. The first 100 results were arranged in decreasing order of "relevance" using the default YouTube algorithm. Videos 1-50 and 51-100 were allocated to a high relevance (HR), and a low relevance (LR) video group, respectively. Multivariable logistic regression models were used to assess the predictors of a video being included in the HR vs. LR groups. Fourteen videos were excluded because they were parodies, songs or stand-up comedies (n = 11), not in English (n = 2) or a remaining part of a previous video (n = 1). Two scales, the video information and quality and index and the medical information and content index (MICI) assessed the overall quality, and the medical content of the videos, respectively. There were no videos from hospitals or academic medical centers. Videos in the HR group had a higher median number of views (186,705 vs. 43,796, p < 0.001), more 'likes' (1119 vs. 224, p < 0.001), channel subscriptions (208 vs. 32, p < 0.001), and 'shares' (519 vs. 98, p < 0.001). Multivariable logistic regression showed that only the 'clinical symptoms' component of the MICI scale was associated with a higher likelihood of a video being included in the HR vs. LR group.(OR 1.86, 95 % CI 1.06-3.28, p = 0.03). YouTube videos presenting clinical symptoms of infectious diseases during epidemics are more likely to be included in the HR group and influence viewers behavior.

Gastric Polyposis: A Rare Cause of Iron Deficiency Anemia in a Patient With Portal Hypertension.

Portal hypertension leading to gastric polyposis has rarely been reported. More common gastric manifestations of portal hypertension are portal hypertensive gastropathy and gastric antral vascular ectasia (GAVE). We report a case of a patient in whom portal hypertension manifested as bleeding gastric polyps leading to transfusion-dependent iron deficiency anemia.

Fusobacterium nucleatum: a rare cause of pyogenic liver abscess.

While pyogenic liver abscesses are uncommon, they are associated with significant mortality and morbidity. Most pyogenic liver abscesses are polymicrobial and are caused by enteric bacteria and anaerobes. Rarely, mono-microbial infections may occur, typically in immunocompromised individuals. We report the unusual case of a 69 year-old immunocompetent female who developed a pyogenic liver abscess due to Fusobacterium nucleatum infection, likely from a dental source. Poor oropharyngeal hygiene seems to have a major role in infection from this organism and therefore F. nucleatum should be considered as a differential for causes of pyogenic liver abscess in such patients. Drainage of the abscess and antibiotic therapy are the mainstays of therapy.