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ObjectiveSeveral factors have been suggested to mediate pain in patients with chronic pancreatitis. However, it is unknown whether these factors are overlapping and if they have cumulative effects on patient-reported outcomes (PROs).DesignWe performed a multicentre cross-sectional study of 201 prospectively enrolled subjects with definitive chronic pancreatitis. All subjects underwent evaluation for pancreatic duct obstruction, abnormalities in pain processing using quantitative sensory testing, and screening for psychological distress (anxiety, depression and pain catastrophising) based on validated questionnaires. Abnormality was defined by normal reference values. PROs included pain symptom severity (Brief Pain Inventory short form) and quality of life (EORTC-QLQ-C30 questionnaire). Associations between pain-related factors and PROs were investigated by linear trend analyses, multiple regression models and mediation analyses.ResultsClinical evaluation suggestive of pancreatic duct obstruction was observed in 29%, abnormal pain processing in 23%, anxiety in 47%, depression in 39% and pain catastrophising in 28%; each of these factors was associated with severity of at least one PRO. Two or more factors were present in 51% of subjects. With an increasing number of factors, there was an increase in pain severity scores (pConclusionPain-related factors in chronic pancreatitis are often present in an overlapping manner and have a cumulative detrimental effect on PROs. These findings support a multidisciplinary strategy for pain management.Trial registration numberThe study was registered with ClinicalTrials.gov (NCT03434392).

Introduction Acute pancreatitis (AP) occurs among patients with pancreas-sufficient cystic fibrosis (PS-CF) but is reportedly less common among patients with pancreas-insufficient cystic fibrosis (PI-CF). The incidence of AP may be influenced by cystic fibrosis transmembrane conductance regulator (CFTR) modulator use. We hypothesized that CFTR modulators would reduce AP hospitalizations, with the greatest benefit in PS-CF. Methods MarketScan (2012-2018) was queried for AP hospitalizations and CFTR modulator use among patients with CF. Multivariable Poisson models that enabled crossover between CFTR modulator treatment groups were used to analyze the rate of AP hospitalizations on and off therapy. Pancreas insufficiency was defined by the use of pancreas enzyme replacement therapy. Results A total of 10,417 patients with CF were identified, including 1,795 who received a CFTR modulator. AP was more common in PS-CF than PI-CF (2.9% vs 0.9%, P = 0.007). Overall, the observed rate ratio of AP during CFTR modulator use was 0.33 (95% confidence interval [CI] 0.10, 1.11, P = 0.07) for PS-CF and 0.38 (95% CI 0.16, 0.89, P = 0.03) for PI-CF, indicating a 67% and 62% relative reduction in AP hospitalizations, respectively. In a subset analysis of 1,795 patients who all had some CFTR modulator use, the rate ratio of AP during CFTR modulator use was 0.36 (95% CI 0.13, 1.01, P = 0.05) for PS-CF and 0.53 (95% CI 0.18, 1.58, P = 0.26) for PI-CF. Discussion CFTR modulator use is associated with a reduction in AP hospitalizations among patients with CF. These observational data support the prospective study of CFTR modulators to reduce AP hospitalizations among patients with CF.

BACKGROUND Symptomatic biliary and gallbladder disorders are common in adults with cystic fibrosis (CF) and the prevalence may rise with increasing CF transmembrane conductance regulator modulator use. Cholecystectomy may be considered, but the outcomes of cholecystectomy are not well described among modern patients with CF. AIM To determine the risk profile of inpatient cholecystectomy in patients with CF. METHODS The Nationwide Inpatient Sample was queried from 2002 until 2014 to investigate outcomes of cholecystectomy among hospitalized adults with CF compared to controls without CF. A propensity weighted sample was selected that closely matched patient demographics, patient's individual comorbidities, and hospital characteristics. The propensity weighted sample was used to compare outcomes among patients who underwent laparoscopic cholecystectomy. Hospital outcomes of open and laparoscopic cholecystectomy were compared among adults with CF. RESULTS A total of 1239 inpatient cholecystectomies were performed in patients with CF, of which 78.6% were performed laparoscopically. Mortality was < 0.81%, similar to those without CF (P = 0.719). In the propensity weighted analysis of laparoscopic cholecystectomy, there was no difference in mortality, or pulmonary or surgical complications between patients with CF and controls. After adjusting for significant covariates among patients with CF, open cholecystectomy was independently associated with a 4.8 d longer length of stay (P = 0.018) and an $18449 increase in hospital costs (P = 0.005) compared to laparoscopic cholecystectomy. CONCLUSION Patients with CF have a very low mortality after cholecystectomy that is similar to the general population. Among patients with CF, laparoscopic approach reduces resource utilization and minimizes post-operative complications.

The coronavirus disease 2019 pandemic led to changes in individuals' behaviors and healthcare delivery. We examined the impact of these changes on the rates and clinical course of acute pancreatitis (AP).Hospitalizations for AP from March 1 through August 31 in 2019 (baseline group) and the same period in 2020 (pandemic group) were retrospectively reviewed. Univariate and multivariate analyses were used for demographics and outcomes.Two hundred eighty subjects (315 admissions) were identified in 2019 and 237 subjects (264 admissions) in 2020. Subjects in the pandemic group were more likely to have systemic inflammatory response syndrome (40% vs 25%, P0.01), pancreatic necrosis (14% vs 10%, P = 0.03), and persistent organ failure (17% vs 9%, P = 0.01) compared with prepandemic. There was no difference in etiology of AP. A multivariable model indicates that increased comorbidities, prior pancreatitis, pancreatic necrosis, and prescription of opiates at discharge were associated with 30-day readmissions during the pandemic.Fewer patients were admitted for AP during the pandemic, suggesting that patients with milder symptoms avoided hospital interaction. Practices followed during the pandemic, especially avoidance of hospitalization and improved efficiency of hospital management, may reduce the burden of pancreatitis care in the future.

Background EUS-guided needle-based confocal laser endomicroscopy (nCLE) has not been widely adopted for the differentiation of pancreatic cystic lesions (PCLs), perhaps due to a perceived difficulty in learning novel CLE image patterns. Hence, we sought to investigate the optimal teaching modality for interpretation of nCLE imaging from PCLs. Methods Sixteen nCLE-naive observers blinded to clinical data were randomized into didactic (classroom-based) versus self-directed (computer-based) teaching groups to review nCLE videos and differentiate mucinous and non-mucinous PCLs. The study was conducted concurrently for both groups in 3 phases. Phase-1-Teaching: both groups received an overview of EUS-nCLE of PCLs. Phase-2-Training: assessment of 20 EUS-nCLE subject-videos; the didactic group had a feedback session with an nCLE expert while the self-directed group received this information via pre-recorded presentation. Phase-3-Testing: assessment of 50 EUS-nCLE subject-videos. Results For all observers (n = 16), the diagnostic accuracy for nCLE-based differentiation of mucinous from non-mucinous PCLs was higher (p=0.005) in the Phase-3-Testing (94.6%, 95%CI: 92-96%) than in Phase-2-Training (89.9%, 95%CI: 85-93%). During Phase-3-Testing, both the didactic and self-directed teaching groups achieved a comparable (p=0.48) diagnostic accuracy of 93.9% and 95.4%, respectively. The interobserver agreement (kappa, standard error) for the differentiation of mucinous from non-mucinous PCLs improved from Phase-2-Training to Phase-3-Testing stage, and was “substantial” for both the didactic (k=0.81, 0.03) and self-directed (k=0.79, 0.03) training groups. Conclusion Notwithstanding didactic and self-directed teaching, a ‘training’ and ‘test’ strategy accomplished high diagnostic accuracies and considerable interobserver agreement among naive observers for EUS-nCLE image differentiation of PCLs; Clinical trial NCT02516488 ( https://clinicaltrials.gov/ct2/show/NCT02516488 )

Cystic fibrosis transmembrane conductance regulator (CFTR) modulators improve pulmonary outcomes in subjects with cystic fibrosis (CF); however, the effects on pancreatic manifestations are not well characterized. We hypothesized that CFTR modulators would improve measures of exocrine pancreatic function and outcomes.We performed a systematic search to identify studies reporting measures of the exocrine pancreas in humans treated with CFTR modulators. Only studies reporting baseline and on-treatment assessments were included.Of 630 identified studies, 41 met inclusion criteria. CFTR modulators reduced acute pancreatitis events by 85% overall (rate ratio 0.15, 95% confidence interval (CI) 0.04, 0.52), with a greater effect seen in the subgroup with pancreas sufficient CF (PS-CF) (rate ratio 0.13 (95% CI 0.03, 0.53). Among 293 subjects with baseline and on-treatment evaluation of pancreas sufficiency, 253 were pancreas insufficient at baseline and 54 (21.3%) converted to pancreas sufficiency. Of 32 subjects with baseline FE-1 values200 mcg/g, 16 (50%) increased to ≥200 mcg/g. Serum trypsin decreased by a mean of 565.9 ng/mL (standard deviation (SD) 311.8), amylase decreased by 38.2 U/L (SD 57.6), and lipase decreased by 232.3 U/L (SD 247.7).CFTR modulator use reduces acute pancreatitis frequency and improves indirect measures of exocrine pancreas function. Future interventional studies that evaluate the mechanism and impact of CFTR modulators on acute pancreatitis and pancreas sufficiency in patients with CFTR dysfunction are warranted.

BACKGROUND AND AIM Esophageal variceal bleeding is a dangerous complication of end-stage liver disease. There is limited information evaluating the hypothesis that medical procedures, specifically electroconvulsive therapy (ECT), may lead to variceal bleeding. The current study aims to determine the risk of variceal bleeding among subjects with cirrhosis who undergo ECT compared with other short medical procedures. METHODS The Nationwide Inpatient Sample (2002-2013) and Nationwide Readmissions Database (2010-2014) were queried using International Classification of Disease, Ninth Revision, codes to evaluate all patients 18 years or older with cirrhosis who underwent ECT, bronchoscopy, or cystoscopy, or who experienced in-hospital seizures. Rates of variceal bleeding and hospital outcomes were compared. Multivariable analysis for readmission rate was performed. RESULTS From the Nationwide Inpatient Sample, a total of 5,442,306 patients with cirrhosis were studied, including 840 (0.02%) patients who underwent ECT. Patients who underwent ECT were more likely to have compensated cirrhosis (P < 0.001). Among patients without ECT, 6.8% had variceal bleeding during admission compared with 0% who underwent ECT. From the Nationwide Readmissions Database, 1,383,853 patients were included, including 357 patients (0.03%) who underwent ECT during index admission. Electroconvulsive therapy did not increase the risk of 30- or 90-day readmission for variceal bleeding or mortality compared with other short medical procedures. CONCLUSIONS Electroconvulsive therapy does not increase the risk of variceal bleeding in subjects with compensated and decompensated cirrhosis. Preoperative optimization of these patients should take the risk of bleeding into account based on current guidelines for variceal surveillance.

Germline genetic testing is recommended for all patients with pancreatic cancer (PC) but uptake rates are low. We implemented a mainstreaming program in oncology clinics to increase testing for PC patients. Genetic counselors trained oncology providers to offer a standardized multigene panel and obtain informed consent using an educational video. Pre-test genetic counseling was available upon request. Otherwise, patients with identified pathogenic variants, strong family history, or questions regarding their results were referred for post-test genetic counseling. We measured rates of testing and genetic counseling visits. From September 2019 to April 2021, 245 patients with PC underwent genetic testing. This represents a 6.5-fold increase in germline testing volume (95% confidence interval 5.2-8.1) compared to previous years. At least one pathogenic or likely pathogenic variant (PV/LPV) was found in 34 (13.9%) patients, including 17 (6.9%) PV/LPVs in high or moderate risk genes and 18 (7.3%) in low risk or recessive genes. Five (2.0%) PVs had implications on treatment selection. 22 of the positive patients (64.7%) and an additional 8 PC patients (1 negative, 3 VUS, and 4 pre-test) underwent genetic counseling during the study period. Genetic counselors saw 2.0 PC patients/month prior to this project, 1.6 PC patients/month during this project, and would have seen 2.2 PC patients/month if all patients with pathogenic variants attended post-test counseling. Conclusions Mainstreaming genetic testing expands access for PC patients without overwhelming genetic counseling resources.

Background/objectives While pain is the predominant symptom of chronic pancreatitis (CP), a subset of patients may experience a painless course. This systematic review aimed to determine the prevalence of primary painless CP. Methods MEDLINE (PubMed), EMBASE and Web of Science Core Collection databases were searched for published studies through September 15, 2020 that included at least 10 consecutive patients with CP and which reported the number with painless CP. The presence of a history of recurrent acute pancreatitis (RAP), exocrine pancreatic insufficiency (EPI), diabetes mellitus (DM) and pancreatic adenocarcinoma (PA) in the painless CP patients was also recorded. A random effects model was used to determine pooled prevalence estimates with 95% confidence intervals (95% CI). Results Among the 5057 studies identified and screened, 42 full-text articles were included in the final analysis. There were a total of 14,277 patients with CP among whom 1569 had painless CP. The pooled prevalence of painless CP was 12% (95% CI 10–15%). Among a subset of studies that reported on calcifications (n = 11), DM (n = 12), EPI (n = 8) and history of RAP (n = 14), the pooled prevalence estimates were 96% (95% CI 73–100%), 51% (95% CI 32–70%), and 47% (95% CI 15–81%), respectively. Alcohol, idiopathic/genetic and other etiologies were attributed to be the cause of painless CP in 32.4%, 56.9% and 8.9% patients, respectively. Conclusion Approximately one in ten patients with CP have primary painless disease with the majority being attributable to an idiopathic/genetic etiology. Further research is needed to determine the optimal management of these patients.

Cystic fibrosis transmembrane conductance regulator (CFTR) modulators significantly improve pulmonary function in patients with cystic fibrosis (CF) but the effect on hepatobiliary outcomes remains unknown. We hypothesized that CF patients on CFTR modulators would have a decreased incidence of cirrhosis compared to patients not on CFTR modulators or on ursodiol.To investigate the effect of CFTR modulators on the development of cirrhosis in patients with CF.A retrospective analysis was performed using Truven MarketScan from January 2012 through December 2017 including all patients with a diagnosis of CF. Patients were excluded if they underwent a liver transplantation or if they had other etiologies of liver disease including viral hepatitis or alcohol use. Subjects were grouped by use of CFTR modulators, ursodiol, dual therapy, or no therapy. The primary outcome was development of cirrhosis. Kaplan-Meier curves estimated the incidence of cirrhosis and log-rank tests compared incidence curves between treatment groups.A total of 7201 patients were included, of which 955 (12.6%) used a CFTR modulator, 529 (7.0%) used ursodiol, 105 (1.4%) used combination therapy, and 5612 (74.3%) used neither therapy. The incidence of cirrhosis was 0.1% at 1 year and 0.7% at 4 years in untreated patients, 5.9% and 10.1% in the Ursodiol group, and 1.0% and 1.0% in patients who received both therapies. No patient treated with CFTR modulators alone developed cirrhosis. Patients on CFTR modulators alone had lower cirrhosis incidence than untreated patients (CFTR modulators are associated with a reduction in the incidence of cirrhosis compared to other therapies in patients with CF.

OBJECTIVES: Abdominal pain is the primary symptom of chronic pancreatitis (CP), but pain is difficult to assess, and objective methods for pain assessment are lacking. The characterization of the sensory component of pain as a surrogate for nociception can be achieved by sensory testing using standardized stimuli. Herein, we describe the rationale for and development of an international consortium to better understand and characterize CP pain.METHODS: A collaboration was initially formed between the University of Aalborg, Johns Hopkins University, and the University of Pittsburgh. This group refined the protocol for pancreatic quantitative sensory testing (P-QST) and then expanded the collaboration with plans for incorporating P-QST into prospective studies.RESULTS: The collaboration has successfully developed a P-QST nomogram. Chronic pancreatitis patients identified with P-QST as having widespread hyperalgesia had higher pain intensity scores, higher prevalence of constant pain, and decreased quality of life. Psychiatric comorbidities were independent of pain phenotypes. Multiple studies are underway to validate these findings and evaluate their utility in clinical trials.CONCLUSIONS: Development of the P-QST Consortium will facilitate collaborative efforts to use P-QST as a means for evaluation and characterization of pain in CP patients, and optimize methods to guide individualized pain management approaches.

Background Esophageal varices are a result of progressive liver disease and portal hypertension. Treatment can be performed with band ligation versus non-selective beta blockers depending on the size of varices, ability to tolerate medications and history of variceal bleeding. Band ligation is an effective intervention with rare but serious complications including bleeding, ulcers and rarely obstruction. Few cases of esophageal obstruction and necrosis caused by banding have been reported, each with varied management from conservative treatment to band removal. Case summary An 89 years old woman with a past medical history of nonalcoholic steatohepatitis cirrhosis presented to the hospital with an inability to swallow one day after screening esophagogastroduodenoscopy where band ligation of esophageal varices was performed for primary prophylaxis. The patient was not able to tolerate her oral secretions. Initial blood work revealed a Model of End Organ Liver Disease score of 7. She was treated with sublingual nitroglycerin for esophageal spasm, a known complication after esophageal banding. When she failed to improve, esophagogastroduodenoscopy was performed and revealed the mucosa surrounding the banded varix was necrosed and blocking the lumen of the esophagus. The band was purposefully dislodged, revealing distal ulceration and stricturing. Within 72 h after band removal, she was tolerating an oral diet. Endoscopy performed 2 wk later revealed an intrinsic stenosis, measuring 8 mm in diameter by 1 cm in length, which was dilated. Conclusion Esophageal obstruction is a complication of variceal banding that should be considered in patients with inability to tolerate oral diet after banding.

BACKGROUND: Cachexia is a wasting syndrome characterized by involuntary loss of >5% body weight due to depletion of adipose and skeletal muscle mass. In cancer, the pro-inflammatory cytokine interleukin-6 (IL-6) is considered a mediator of cachexia and a potential biomarker, but the relationship between IL-6, weight loss, and cancer stage is unknown. In this study we sought to evaluate IL-6 as a biomarker of cancer cachexia while accounting for disease progression. METHODS: We retrospectively studied 136 subjects with biopsy-proven pancreatic ductal adenocarcinoma (PDAC), considering the high prevalence of cachexia is this population. Clinical data were abstracted from subjects in all cancer stages, and plasma IL-6 levels were measured using a multiplex array and a more sensitive ELISA. Data were evaluated with univariate comparisons, including Kaplan-Meier survival curves, and multivariate Cox survival models. RESULTS: On multiplex, a total of 43 (31.4%) subjects had detectable levels of plasma IL-6, while by ELISA all subjects had detectable IL-6 levels. We found that increased plasma IL-6 levels, defined as detectable for multiplex and greater than median for ELISA, were not associated with weight loss at diagnosis, but rather with the presence of metastasis (p5% weight loss was not associated with worse survival, increased plasma IL-6 by either methodology was. CONCLUSION: Circulating IL-6 levels do not correlate with weight loss (i.e., cachexia), but rather with advanced cancer stage. This suggests that IL-6 may mediate wasting, but should not be considered a diagnostic biomarker for PDAC-induced cachexia.

OBJECTIVES We hypothesized that hospitalizations in cystic fibrosis (CF) would reflect the development of age-related comorbidities. METHODS A retrospective analysis was performed using the Nationwide Inpatient Sample (2002-2017). Hospitalizations for which the principal diagnosis was CF were analyzed regarding age at discharge and presence of comorbidities. Trends were assessed for significance using the Cochran-Armitage test. RESULTS The mean age of patients hospitalized for CF increased from 19.7 years in 2002 to 23.0 years in 2017 (P = 0.017). Several comorbidities are more than 10 times more prevalent among adults as compared with children, including congestive heart failure, substance abuse, and chronic kidney disease (P < 0.001). In addition, diabetes with chronic complications was more prevalent in adults than children (10.0% vs 3.9%; P < 0.001), as was hypertension (7.2% vs 1.3%; P < 0.001) and osteoporosis (10.2% vs 1.9%; P < 0.001). More than 65% of CF hospitalizations in 2017 were in individuals older than 18 years. CONCLUSIONS Hospitalizations for adults with CF are increasing, and individuals with CF are developing age-related comorbidities. Providers equipped to manage the health care needs of adults need to be ready and able to care for this unique and growing patient population.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel coronavirus that causes coronavirus disease 2019 (COVID-19) in human beings, has caused a serious public health issue.

Introduction Chronic pancreatitis is a chronic inflammatory disease, which progresses to fibrosis. Currently there are no interventions to delay or stop the progression to irreversible organ damage. In this study, we assessed the tolerability and feasibility of administering soy bread to reduce circulating inflammatory mediators. Methods Subjects with chronic pancreatitis diagnosed using the American Pancreatic Association diagnostic guidelines were enrolled. During the dose escalation (DE) phase, subjects received one week of soy bread based using a 3 + 3 dose-escalation design, which was then followed by a maximally tolerated dose (MTD) phase with four weeks of intervention. Dose-limiting toxicities (DLTs) were monitored. Plasma cytokine levels were measured using a Meso Scale Discovery multiplex assay kit. Isoflavonoid excretion in 24-h urine collection was used to measure soy bread compliance. Results Nine subjects completed the DE phase, and one subject completed the MTD phase without any DLTs at a maximum dosage of three slices (99 mg of isoflavones) per day. Reported compliance to soy bread intervention was 98%, and this was confirmed with urinary isoflavones and their metabolites detected in all subjects. There was a significant decline in the TNF-α level during the DE phase (2.667 vs 2.382 pg/mL, p = 0.039); other levels were similar. Conclusions In this feasibility study, there was excellent compliance with a short-term intervention using soy bread in chronic pancreatitis. Reduction was seen in at least one pro-inflammatory cytokine with short-term intervention. Larger cohorts and longer interventions with soy are warranted to assess the efficacy of reducing pro-inflammatory mediators of disease.

Insulin resistance (IR) increases the risk of index colorectal cancer (CRC) development. Limited data exist on IR values, lifestyle, and anthropometric alterations of patients after CRC diagnosis, a population at high risk for CRC recurrence.This is a retrospective cohort study using the National Health and Nutrition Examination Survey (NHANES), 1999-2010. We identified patients with and without prior CRC above age 50. Our outcomes were lifestyle, anthropometric measures, and IR measured using the triglyceride to high-density lipoprotein ratio and the homeostasis model assessment IR.There were 146,841 patients with prior CRC and 26,979,507 without prior cancer (controls) in our cohort. Prior patients with CRC were significantly older than controls (75.8 vs 62.3, P0.01), however, there were no significant differences in gender, ethnicity, income, caloric intake, tobacco use or alcohol consumption between both groups. Multivariate analysis revealed no difference between prior patients with CRC and controls in triglyceride to high-density lipoprotein ratio (adjusted percentage change = -2.17; 95% CI: -27.96 to 18.43) or homeostasis model assessment IR (adjusted percentage change = -6.85; 95% CI: -35.74 to 15.90). Despite similar weight at age 25, prior CRC subjects had lower weights compared to controls (at time of NHANES survey, one and 10 years before survey and greatest weight). Furthermore prior CRC subjects gained less weight in the 10 years before survey.Patients with prior CRC above age 50 have no conclusive evidence of increased IR compared to non-CRC controls. This is possibly due to lesser weight gain in the peri-CRC diagnosis or treatment period. Future efforts should focus on alternate etiologies for the increased CRC recurrence in this high-risk group.

Cachexia is a multifactorial syndrome characterized by weight loss and tissue wasting, which is associated with reduced quality of life, responsiveness to chemotherapy, and decreased survival. We aim to determine whether changes in plasma fatty acid content in pancreatic ductal adenocarcinoma (PDAC): 1) are predictive of developing cachexia, and 2) whether these changes are influenced by other clinical parameters, like diabetes, that could contribute to malnutrition. Treatment-naïve metastatic PDAC subjects (n=51) were enrolled in NCT01280058 in which plasma samples and clinical data were collected prior to treatment. Subjects were assigned to either weight stable ( Citation Format: Kristyn Gumpper, Phil A. Hart, Martha Belury, Olivia Crowe, Rachel M. Cole, Niharika Badi, Alice Hinton, Mitchell L. Ramsey, Anne Noonan, Darwin L. Conwell, Zobeida Cruz-Monserrate. Plasma fatty acid levels in treatment-naïve metastatic pancreatic cancer patients are associated with clinical indicators of cachexia [abstract]. In: Proceedings of the AACR Virtual Special Conference on Pancreatic Cancer; 2020 Sep 29-30. Philadelphia (PA): AACR; Cancer Res 2020;80(22 Suppl):Abstract nr PO-022.

Chronic pancreatitis is a disease that leads to irreversible changes in the pancreatic morphology and function. The loss of function can lead to diabetes mellitus and exocrine pancreatic insufficiency. The inflammation and fibrosis can also lead to other complications including a chronic abdominal pain syndrome, metabolic bone disease, and pancretic cancer. This article reviews our current understanding of the mechanisms and management of these complications of chronic pancreatitis.

Positive surgical margins (PSMs) may reflect incomplete surgical resection, while extraprostatic extension (EPE) could suggest that complete tumor resection is more difficult. This study evaluated cases with both EPE and PSMs in robotic-assisted radical prostatectomy (RARP) specimens to determine the respective locations of each. A single institutional retrospective review of RARP performed between 2007 and 2009 was conducted to identify cases with both EPE and PSM. Prostates were entirely submitted and processed in whole mount format. All locations of EPE and PSM were recorded as was the size of the largest focus of EPE and PSM. About 8.5 % (112/1,315) of RARP had both EPE and PSM. Analysis of cases with concurrent EPE and PSM revealed that EPE occurred most commonly in the mid-gland, particularly in the posterolateral mid-prostate. In contrast, PSM was most frequent at the base (bladder neck), specifically the anterior base. 51.8 % of the cases had EPE and PSM in discordant locations, 19.6 % had EPE and PSM in the same location, and 28.6 % had areas of EPE and PSM both in the same location as well as in different locations. Cases with both concordant and discordant locations of EPE and PSM had significantly more high-risk features including higher tumor volume, more frequent positive nodes, and more frequent Gleason score ≥ 8 compared to concordant or discordant subgroups. PSMs frequently did not occur in the same location as EPE. A better understanding of where EPE and PSMs occur may help guide surgical technique to decrease residual tumor.

High immunohistochemical expression of carbonic anhydrase IX (CAIX) is found in clear cell renal cell carcinoma (ccRCC), but no studies have assessed CAIX in metastatic ccRCC (mccRCC) of the lung. As 75% of patients with mccRCC show lung involvement, characterization of protein expression in these lesions is warranted. This investigation analyzed CAIX immunohistochemical expression in pulmonary/pleural tumors including mccRCC (n = 22), mesothelioma (n = 19), squamous cell carcinoma (n = 27), small cell carcinoma (n = 9), and adenocarcinoma (n = 49), as well as other mesothelial lesions (n = 4). Membranous immunoreactivity was semiquantitatively evaluated for percent of cells stained and intensity. All cases of mccRCC (1+, 4.5%; 3+, 95.5%) and mesothelioma (2+, 10.5%; 3+, 89.5%) expressed CAIX. Most cases of lung squamous cell carcinoma (0, 11.1%; 1+, 25.9%; 2+, 22.2%; 3+, 40.7%) and small cell carcinoma were reactive (0, 11.1%; 1+, 22.2%; 2+, 33.3%; 3+, 33.3%), while CAIX was detected less frequently in pulmonary adenocarcinoma (0, 61.2%; 1+, 16.3%; 2+, 12.2%; 3+, 10.2%). In addition, CAIX was positive in adenomatoid tumor (3+, 100%) and mesothelial hyperplasia (3+, 100%). We demonstrate that CAIX is sensitive for mccRCC within the lung and a novel immunohistochemical marker for mesothelial proliferations, notably mesothelioma. Variable immunoreactivity is present among primary pulmonary epithelial tumors. Knowledge of expression overlap between these entities may prevent an incorrect interpretation of immunohistochemical results, particularly when limited tissue is available. As new carbonic anhydrase inhibitors are being evaluated, testing additional tumors for CAIX may lead to novel treatment options.

Objectives Inflammatory bowel disease (IBD) is associated with an increased risk of colorectal cancer (CRC) compared to patients without IBD. There is a lack of population-based data evaluating the in-patient surgical outcomes of CRC in IBD patients. We sought to compare the hospital outcomes of CRC surgery between patients with and without IBD. Methods We used the National Inpatient Sample (2008-2012) and Nationwide Readmissions Database (NRD, 2013) and selected all adult patients (age ≥18 years) with ulcerative colitis (UC) or Crohn's disease (CD) who underwent CRC surgery. Multivariate analysis for in-patient outcomes of postoperative complications, health-care resource utilization, readmission rate, and mortality were performed. Results A total of 397,847 patients underwent CRC surgery from 2008 to 2012, of which 0.8% (3,242) had IBD. Compared to CRC in non-IBD patients, CRC in IBD patients had longer length of stay (adjusted coefficient (AC) 0.86 days, 95% confidence interval (CI): 0.42, 1.30), more likely developed postoperative complications (adjusted odds ratio (AOR) 1.26, 95% CI: 1.06, 1.50), including postoperative infection (AOR 1.69, 95% CI: 1.20, 2.38) and deep vein thrombosis (AOR 2.42, 95% CI: 1.36, 4.28), and more frequently required blood transfusion (AOR 1.59, 95% CI: 1.30, 1.94). CRC in IBD patients was more likely to be readmitted within 30 days (AOR 1.44, 95% CI: 1.01, 2.04). Conclusion At a population level, IBD adversely impacts outcomes at the time of CRC surgery.