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BACKGROUND AND AIMS: Many patients undergoing total pancreatectomy with islet autotransplant (TPIAT) for severe, refractory chronic pancreatitis or recurrent acute pancreatitis have a history of endoscopic retrograde cholangiopancreatography (ERCP). Using data from the multicenter POST (Prospective Observational Study of TPIAT) cohort, we aimed to determine clinical characteristics associated with ERCP and the effect of ERCP on islet yield. METHODS: Using data from 230 participants (11 centers), demographics, pancreatitis history, and imaging features were tested for association with ERCP procedures. Logistic and linear regression were used to assess association of islet yield measures with having any pre-operative ERCPs and with the number of ERCPs, adjusting for confounders. RESULTS: 175 (76%) underwent ERCPs [median number of ERCPs (IQR) 2 (1–4)]. ERCP was more common in those with obstructed pancreatic duct (p=0.0009), pancreas divisum (p=0.0009), prior pancreatic surgery (p=0.005), and longer disease duration (p=0.004). A greater number of ERCPs was associated with disease duration (p

Gastroparesis, which can be viewed as a syndrome featuring nausea, vomiting, and abdominal pain, and associated other symptoms and findings, is increasingly seen by surgeons. Gastroparesis is associated with a number of gastrointestinal anatomic and physiologic findings. This article reviews the use of bioelectric therapy of neuromodulation, via gastric electrical stimulation, for patients with drug refractory gastroparesis syndromes including surgical aspects of device placement and subsequent management. In addition to an overall approach to the placement and subsequent management of gastric electrical stimulation devices, several newer concepts are discussed. The role of pyloric dysfunction in gastroparesis is also discussed including how stimulation devices and pyloric therapies may be used in concert. The additions of full-thickness gastrointestinal biopsies along with other physiologic, including GI electrophysiology, as well as some serologic measures, are also discussed. In addition, evolving approaches and emerging technologies for bioelectric neuromodulation of the gastrointestinal tract are introduced. Gastroparesis syndromes can be approached in a systematic manner based on known pathophysiology and when indicated can be helped with surgical therapies including neuromodulation.

Artificial intelligence (AI) is emerging as a key component in diagnostic medical imaging, including echocardiography. AI with deep learning has already been used with automated view labeling, measurements, and interpretation. As the development and use of AI in echocardiography increase, potential concerns may be raised by cardiac sonographers and the profession. This report, from a sonographer's perspective, focuses on defining AI, the basics of the technology, identifying some current applications of AI, and how the use of AI may improve patient care in the future., Highlights • AI will have a strong role in echocardiography. • AI will guide image acquisition and optimization. • AI for image analysis may aid in interpretation. • AI is a tool that will not replace sonographers but will help them be more efficient.

Background: The International Study Group for Pancreatic Surgery provides globally accepted definitions for reporting of complications after pancreatic surgery. This International Study Group for Pancreatic Surgery project aims to provide a standardized framework for reporting of the results of operative treatment for chronic pancreatitis. Methods: An International Study Group for Pancreatic Surgery project circulation list was created with pre-existing and new members and including gastroenterologists in addition to surgeons. A computerized search of the literature was undertaken for articles reporting the operative treatment of chronic pancreatitis. The results of the literature search were presented at the first face-to-face meeting of this International Study Group for Pancreatic Surgery project group. A document outlining proposed reporting standards was produced by discussion during an initial meeting of the International Study Group for Pancreatic Surgery. An electronic questionnaire was then sent to all current members of the International Study Group for Pancreatic Surgery. Responses were collated and further discussed at international meetings in North America, Europe, and at the International Association of Pancreatology World Congress in 2019. A final consensus document was produced by integration of multiple iterations. Results: The International Study Group for Pancreatic Surgery consensus standards for reporting of surgery in chronic pancreatitis recommends 4 core domains and the necessary variables needed for reporting of results: clinical baseline before operation; the morphology of the diseased gland; a new, standardized, operative terminology; and a minimum outcome dataset. The 4 domains combine to give a comprehensive framework for reports. Conclusion: Adoption of the 4 domains of the International Study Group for Pancreatic Surgery reporting standards for surgery for chronic pancreatitis will facilitate comparison of results between centers and help to improve the care for patients with this debilitating disease.

Observations on strain behaviour and direct demonstrations of natural selection establish that the scrapie agent and prions in general are able to evolve. Accordingly, it is conceivable that atypical non-contagious scrapie in sheep and goats can transform to classical contagious scrapie under particular circumstances. In consequence, atypical scrapie can be regarded as a latent hazard that warrants comprehensive risk assessment and biosecurity preparedness planning. Evidence for this proposition comes from differences in the expression of atypical and classical scrapie that may make scrapie contagious, historical records of scrapie in Western Europe, and contemporary accounts of the epidemiology of atypical scrapie. Biosecurity preparedness can be based on current knowledge of pathophysiology and epidemiology and can be built around a three-stage model for the endogenous emergence of a propagating epidemic of scrapie. The first stage concerns the occurrence of atypical scrapie. The second stage concerns the acquisition of communicability in prion populations provided by atypical scrapie and the third stage concerns circumstances allowing disease transmission and the initiation of a propagating epidemic. The range of component causes envisaged for possible outbreaks of endogenous classical scrapie is broad. However, exposure of sheep and goats to cyanobacterial toxins qualifies for special attention.

Background Program directors use United States Medical Licensing Exam (USMLE) scores as criteria for ranking applicants. First-time pass rates of the American Board of Surgery (ABS) Qualifying (QE) and Certifying (CE) Examinations have become important measures of residency program quality. USMLE Step 1 will become pass/fail in 2022. Study design American Board of Surgery QE and CE success rates were assessed considering multiple characteristics of highly ranked (top 20) applicants to 22 general surgery programs in 2011. Chi-square, t-test, Wilcoxon Rank sum, linear and logistic regression were used, as appropriate. Results The QE and CE first attempt pass rates were 96% (235/244) and 86% (190/221), respectively. QE/CE success was not significantly associated with sex, race, research experience, or publications. Alpha Omega Alpha (AΩA) status was associated with success on the index CE (98% vs 83%; p = 0.008). Step 1 and Step 2 Clinical Knowledge (CK) scores of surgeons who passed QE on their first attempt were higher than scores of those who failed (Step 1: 233 vs 218; p = 0.016); (Step 2CK: 244 vs 228, p = 0.009). For every 10-point increase in Step 1 and 2CK scores, the odds of passing CE on the first attempt increased 1.5 times (95% CI 1.12, 2.0; p = 0.006) and 1.5 times (95% CI 1.11, 2.02, p = 0.008), respectively. For every 10-point increase in Steps 1 and 2CK scores, the odds of passing the QE on the first attempt increased 1.85 times (95% CI 1.11, 3.09; p = 0.018) and 1.86 times (95% CI 1.14, 3.06, p = 0.013), respectively. Conclusions USMLE Step 1 and Step 2 CK examination scores correlate with American Board of Surgery QE and CE performance and success. The USMLE decision to transition Step 1 to a pass/fail examination will require program directors to identify other factors that predict ABS performance for ranking applicants.

Circulating microRNAs (miRNAs) can be biomarkers for diagnosis and progression of several pathophysiological conditions. In a cohort undergoing total pancreatectomy with islet autotransplantation (TPIAT) from the multicenter Prospective Observational Study of TPIAT (POST), we investigated associations between a panel of circulating miRNAs (hsa-miR-375, hsa-miR-29b-3p, hsa-miR-148a-3p, hsa-miR-216a-5p, hsa-miR-320d, hsa-miR-200c, hsa-miR-125b, hsa-miR-7-5p, hsa-miR-221-3p, hsa-miR-122-5p) and patient, disease and islet-isolation characteristics. Plasma samples ( n = 139) were collected before TPIAT and miRNA levels were measured by RTPCR. Disease duration, prior surgery, and pre-surgical diabetes were not associated with circulating miRNAs. Levels of hsa-miR-29b-3p ( P = 0.03), hsa-miR-148a-3p ( P = 0.04) and hsa-miR-221-3p ( P = 0.01) were lower in those with genetic risk factors. Levels of hsa-miR-148a-3p ( P = 0.04) and hsa-miR-7-5p ( P = 0.04) were elevated in toxic/metabolic disease. Participants with exocrine insufficiency had lower hsa-miR-29b-3p, hsa-miR-148a-3p, hsa-miR-320d, hsa-miR-221-3p ( P < 0.01) and hsa-miR-375, hsa-miR-200c-3p, and hsa-miR-125b-5p ( P < 0.05). Four miRNAs were associated with fasting C-peptide before TPIAT (hsa-miR-29b-3p, r = 0.18; hsa-miR-148a-3p, r = 0.21; hsa-miR-320d, r = 0.19; and hsa-miR-221-3p, r = 0.21; all P < 0.05), while hsa-miR-29b-3p was inversely associated with post-isolation islet equivalents/kg and islet number/kg ( r = −0.20, P = 0.02). Also, hsa-miR-200c ( r = 0.18, P = 0.03) and hsa-miR-221-3p ( r = 0.19, P = 0.03) were associated with islet graft tissue volume. Further investigation is needed to determine the predictive potential of these miRNAs for assessing islet autotransplant outcomes.

Mesenchymal stem cells (MSCs) are proven to be beneficial in islet transplantation, suggesting a potential therapeutic role of them in total pancreatectomy with islet autotransplantation (TP-IAT) for chronic pancreatitis (CP) patients. We investigated whether MSCs derived from CP patients are suitable for use in autologous cell therapy. MSCs from healthy donors (H-MSCs) and CP patients (CP-MSCs) were studied for phenotype, colony formation potential, multilineage differentiation ability, proliferation, senescence, secretory characters, and immunosuppressive functions. The potential protective effect of CP-MSCs was evaluated on hypoxia-induced islet cell death. Cell surface markers were similar between H-MSCs and CP-MSCs, as well as the ability of colony formation, multilineage differentiation, secretion of vascular endothelial growth factor and transforming growth factor (TGF-β), senescence, and inhibition of T cells proliferation in vitro. We found that growth differentiation factor 6 and hepatocyte growth factor (HGF) were significantly downregulated, whereas TGFβ and matrix metalloproteinase-2 were significantly upregulated in CP-MSCs compared with H-MSCs, among 84 MSC-related genes investigated in this study. MSCs from CP patients secreted less HGF, compared with the H-MSCs. A higher interferon-γ-induced indoleamine 2,3-dioxygenase expression was observed in CP-MSCs compared to H-MSCs. Moreover, CP-MSCs prevented hypoxia-induced β cell deaths to a similar extent as H-MSCs. Regardless of moderate difference in gene expression, CP-MSCs possess similar immunomodulatory and prosurvival functions to H-MSCs, and may be suitable for autologous cell therapy in CP patients undergoing TP-IAT. Stem Cells Translational Medicine 2019;8:418–429

Background Best practice to select patients with chronic pancreatitis for surgical management with total pancreatectomy with islet autotransplantation (TPIAT) is in evolution as new discoveries are made in the pathogenesis of chronic pancreatitis. Study Design A prospectively maintained database of patients undergoing TPIAT was reviewed. Islet function was inferred from daily insulin requirement. Pain relief was evaluated by healthcare use and narcotic use. Quality of life (QOL) was measured with the RAND 12-Item Short Form Survey. Results One hundred and ninety-five patients (141 women, aged 40.3 years, BMI 26.5 kg/m 2 ) underwent TPIAT. Mean duration of disease before operation was 8.1 years. Fifty-six (29%) patients had pancreatic operations before TPIAT, 37 (19%) patients were diabetic preoperatively, and 52 (27%) patients were smokers. A mean of 3,253 islet equivalents transplanted/kg were harvested. Insulin independence was achieved in 29%, 28%, and 23% of patients at 1, 2, and 5 years postoperative. Nonsmokers with a shorter duration of chronic pancreatitis and no earlier pancreas operation were more likely to be insulin free. Median number of preoperative emergency department visits and hospitalizations were 6.6 and 4.3 annually, respectively, compared with 0 at 1, 2, and 5 years postoperative. Median oral morphine equivalents were 214 mg/kg preoperation and 60, 64, 69, at 1, 2, 5 years postoperative. Preoperative, 1, 2, 5 years postoperative QOL scores were 29, 36, 34, and 33 (physical; p Conclusions Total pancreatectomy with islet autotransplantation is a durable operation, with islet function, pain relief, and QOL improvements persisting to 5 years postoperative. Patients with genetic pancreatitis, short duration of disease, and nonsmokers have superior outcomes.

Islet engraftment after transplantation is impaired by high rates of islet/β cell death caused by cellular stressors and poor graft vascularization. We studied whether cotransplantation of ex vivo expanded autologous bone marrow‐derived mesenchymal stem cells (MSCs) with islets is safe and beneficial in chronic pancreatitis patients undergoing total pancreatectomy with islet autotransplantation. MSCs were harvested from the bone marrow of three islet autotransplantation patients and expanded at our current Good Manufacturing Practices (cGMP) facility. On the day of islet transplantation, an average dose of 20.0 ± 2.6 ×106 MSCs was infused with islets via the portal vein. Adverse events and glycemic control at baseline, 6, and 12 months after transplantation were compared with data from 101 historical control patients. No adverse events directly related to the MSC infusions were observed. MSC patients required lower amounts of insulin during the peritransplantation period (p = .02 vs. controls) and had lower 12‐month fasting blood glucose levels (p = .02 vs. controls), smaller C‐peptide declines over 6 months (p = .01 vs. controls), and better quality of life compared with controls. In conclusion, our pilot study demonstrates that autologous MSC and islet cotransplantation may be a safe and potential strategy to improve islet engraftment after transplantation. (Clinicaltrials.gov registration number: {"type":"clinical-trial","attrs":{"text":"NCT02384018","term_id":"NCT02384018"}}NCT02384018). stem cells translational medicine 2018;7:11–19

Stresses encountered during human islet isolation lead to unavoidable β-cell death after transplantation. This reduces the chance of insulin independence in chronic pancreatitis patients undergoing total pancreatectomy and islet autotransplantation. We tested whether harvesting islets in carbon monoxide-saturated solutions is safe and can enhance islet survival and insulin independence after total pancreatectomy and islet autotransplantation. Chronic pancreatitis patients who consented to the study were randomized into carbon monoxide (islets harvested in a carbon monoxide-saturated medium) or control (islets harvested in a normal medium) groups. Islet yield, viability, oxygen consumption rate, β-cell death (measured by unmethylated insulin DNA), and serum cytokine levels were measured during the peri-transplantation period. Adverse events, metabolic phenotypes, and islet function were measured prior and at 6 months post-transplantation. No adverse events directly related to the infusion of carbon monoxide islets were observed. Carbon monoxide islets showed significantly higher viability before transplantation. Subjects receiving carbon monoxide islets had less β-cell death, decreased CCL23, and increased CXCL12 levels at 1 or 3 days post transplantation compared with controls. Three in 10 (30%) of the carbon monoxide subjects and none of the control subjects were insulin independent. This pilot trial showed for the first time that harvesting human islets in carbon monoxide-saturated solutions is safe for total pancreatectomy and islet autotransplantation patients.

Objectives A selective therapy for pancreatitis is total pancreatectomy and islet autotransplantation. Outcomes and geographical variability of patients who had total pancreatectomy (TP) alone or total pancreatectomy with islet autotransplantation (TPIAT) were assessed. Methods Data were obtained from the Healthcare Cost and Utilization Project National Inpatient Sample database. Weighed univariate and multivariate analyses were performed to determine the effect of measured variables on outcomes. Results Between 2002 and 2013, there were 1006 TP and 825 TPIAT in patients with a diagnosis of chronic pancreatitis, and 1705 TP and 830 TPIAT for any diagnosis of pancreatitis. The majority of the TP and TPIAT were performed in larger urban hospitals. Costs were similar for TP and TPIAT for chronic pancreatitis but were lower for TPIAT compared with TP for any type of pancreatitis. The trend for TP and TPIAT was significant in all geographical areas during the study period. Conclusions There is an increasing trend of both TP and TPIAT. Certain groups are more likely to be offered TPIAT compared with TP alone. More data are needed to understand disparities and barriers to TPIAT, and long-term outcomes of TPIAT such as pain control and glucose intolerance need further study.

Gastroparesis is a condition characterized by impaired gastric motility that may result in weight loss and malnutrition. There have been promising studies demonstrating improvement in symptoms after gastric electrical stimulation (GES) implantation for medically refractory gastroparetics [1-10]. With the heterogeneous population of gastroparetics, the aim of this study was to assess if etiology correlated with response to GES.A retrospective review and analysis was performed on patients who underwent GES over a 10-year period at a single institution. Each patient was stratified into an etiological subset (diabetes, idiopathic, post-surgical). Patients were compared by demographics, medical and surgical history, subsequent GES explantation vs continued therapy, need for supplemental nutrition postoperatively, weight gain, weight loss or weight maintenance, and readmission rates.183 patients underwent GES from 2005 to 2015. 50% were diabetic (n = 91), 42% idiopathic (n = 76), and 9% post-surgical (n = 16). Diabetic patients (DM) demonstrated the highest likelihood of continued therapy compared to post-surgical (PS) and idiopathic patients (ID) (54.7% vs 9.5% vs 35.8%, respectively, p 0.05). DM patients saw a greater incidence of weight gain 4 kg, compared to PS and IS patients (67.6% vs 8.1% vs. 24.3%, respectively, p 0.05). ID patients were most likely to have it removed compared to DM and PS patients (65.7% vs 28.6% vs 5.7%, respectively, p = 0.05). PS patients were least likely to have their GES removed. They were also least likely to utilize supplemental nutrition compared to DM and ID (9.4% vs 49.1% vs 41.51%, respectively, p 0.05).Patients with gastroparesis had different clinical outcomes after GES therapy based on underlying etiology. By gaining a better understanding of the effects of GES, it can be offered to the appropriate patient.

Islet cell transplantation has limited effectiveness because of an instant blood-mediated inflammatory reaction (IBMIR) that occurs immediately after cell infusion and leads to dramatic β-cell death. In intraportal islet transplantation models using mouse and human islets, we demonstrated that α-1 antitrypsin (AAT; Prolastin-C), a serine protease inhibitor used for the treatment of AAT deficiency, inhibits IBMIR and cytokine-induced inflammation in islets. In mice, more diabetic recipients reached normoglycemia after intraportal islet transplantation when they were treated with AAT compared with mice treated with saline. AAT suppressed blood-mediated coagulation pathways by diminishing tissue factor production, reducing plasma thrombin-antithrombin complex levels and fibrinogen deposition on islet grafts, which correlated with less graft damage and apoptosis. AAT-treated mice showed reduced serum tumor necrosis factor-α levels, decreased lymphocytic infiltration, and decreased nuclear factor (NF)-κB activation compared with controls. The potent anti-inflammatory effect of AAT is possibly mediated by suppression of c-Jun N-terminal kinase (JNK) phosphorylation. Blocking JNK activation failed to further reduce cytokine-induced apoptosis in β-cells. Taken together, AAT significantly improves islet graft survival after intraportal islet transplantation by mitigation of coagulation in IBMIR and suppression of cytokine-induced JNK and NF-κB activation. AAT-based therapy has the potential to improve graft survival in human islet transplantation and other cellular therapies on the horizon.

The impact of lymph node (LN) status and lymphadenectomy (LA) on survival in pancreatic neuroendocrine tumors (pNETs) remains controversial. We evaluated the impact of tumor extension and grade on nodal metastasis and survival. Surgical pNET patients were queried in the Surveillance Epidemiology and End Results (SEER) database (1998–2012, N = 981). Factors associated with LN status were analyzed by logistic regression and by Cox analyses. For T1–T2 tumors, N status was associated only with tumor size. N status (p = 0.001), grade (p

Many patients with recurrent acute and chronic pancreatitis who are candidates for total pancreatectomy and islet cell autotransplantation (TPIAT) undergo endoscopic retrograde cholangiopancreatography (ERCP). However, little is known on the impact of ERCP on TPIAT outcomes. We aimed to explore the effect of antecedent ERCP on islet yield and postoperative insulin requirement after TPIAT.Through a prospectively maintained database, we identified patients who underwent TPIAT at our institution between 2009 and 2016. After adjusting for confounders, islet cell yield and postoperative insulin requirement were compared between subjects who did and did not undergo ERCP within 2 years prior to TPIAT.Data were available on 167 TPIAT patients during the study period; 105 (62.9%) had undergone ERCP within 2 years prior. Prior ERCP was not associated with a reduction in islet equivalents per patient kilogram (odds ratio, 1.37; 95% confidence interval, 0.75-2.5; P = 0.31). Antecedent ERCP was not associated with increased postoperative insulin requirement among patients with no diabetes undergoing TPIAT (odds ratio, 0.85; 95% confidence interval, 0.39-1.83; P = 0.67).Antecedent ERCP does not appear to have a deleterious impact on islet cell yield during TPIAT. Additional multicenter data are needed to more clearly determine the impact of ERCP in this context.

BACKGROUND: Chronic opiate use leads to a sensitized behavioral response to acute pain, which in turn, leads to escalating doses of opiates. This study was designed to test the hypothesis that chronic opiate usage is also associated with a sensitized neurobiological response to acute pain in individuals that have used prescription opiates for 6 or more months. METHODS: Fourteen patients with non-alcoholic chronic pancreatitis that have been taking prescription opiates for 6 or more months and 14 gender matched, non-opiate using controls were enrolled. Functional neuroimaging data was acquired while participants received blocks of thermal stimulation to their wrist (individually-tailored to their pain threshold). RESULTS: Self-reported pain was significantly greater in opiate using patients (3.4±3.4) than controls (0.2±0.8: Brief Pain Inventory p

Infiltrating macrophages can induce inflammation by secretion of proinflammatory cytokines and contribute to islet graft loss shortly after islet transplantation. In this study, we tested the mechanistic effects of AAT in mitigating macrophage mediated inflammation in an intrahepatic islet transplantation model in which human islets (2500 islet equivalent numbers) were transplanted into NOD-SCID mice that had been rendered diabetic (blood glucose >350mg/dl) by streptozotocin treatment. AAT (Prolastin-C, Grifols) was given to recipients intraperitoneally at 4 mg/mouse, every two days for 14 days, beginning before transplantation. In those recipients receiving AAT (n=29), 69.0% reached normoglycemia, compared to 35.7% in controls (n=28, p=0.002, logrank test) at 30 days post transplantation. Compared to mice treated with vehicle, AAT-treated mice had lower serum levels of interleukin 1 β (IL-1β), interferon- γ (IFN-γ) and interleukin 6 (IL-6), at day 1 post transplantation. To explore potential cell target(s) of AAT action, we analyzed activation of macrophages infiltrated into the liver after transplantation. Fewer M1 macrophages were observed in AAT-treated mice than in controls. To measure the effects of AAT on macrophage activation, we added AAT to Raw264.7 cells stimulated with IFN-γ in vitro. Expressions of M1 markers (iNOS, CD11c, TNFα, and IL-6) were dramatically decreased in AAT-treated cells compared to vehicle-treated controls. Co-culture of IFN-γ activated macrophages with islets led to islet cell apoptosis. Addition of AAT in the co-culture system reduced macrophage activation and protected islet cells from apoptosis. In summary, AAT treatment significantly enhances human islet graft survival and function after transplantation into the liver of NOD-SCID mice, in part by suppression of macrophage activation and pro-inflammatory cytokine production. Disclosure W. Gou: None. J. Wang: None. D. Kim: None. L. Song: None. C. Strange: Research Support; Self; Grifols, CSL Behring, Shire. Consultant; Self; Shire. Stock/Shareholder; Self; Abeona. Consultant; Self; CSL Behring. Research Support; Self; Adverum. Consultant; Self; Adverum. Research Support; Self; MatRx. D. Adams: None. K. Morgan: None. H. Wang: None.

The objective of this study was to assess the capacity of adipose-derived mesenchymal stem cells (ASCs) to mitigate disease progression in an experimental chronic pancreatitis mouse model. Chronic pancreatitis (CP) was induced in C57BL/6 mice by repeated ethanol and cerulein injection, and mice were then infused with 4 × 105 or 1 × 106 GFP+ ASCs. Pancreas morphology, fibrosis, inflammation, and presence of GFP+ ASCs in pancreases were assessed 2 weeks after treatment. We found that ASC infusion attenuated pancreatic damage, preserved pancreas morphology, and reduced pancreatic fibrosis and cell death. GFP+ ASCs migrated to pancreas and differentiated into amylase+ cells. In further confirmation of the plasticity of ASCs, ASCs co-cultured with acinar cells in a Transwell system differentiated into amylase+ cells with increased expression of acinar cell-specific genes including amylase and chymoB1. Furthermore, culture of acinar or pancreatic stellate cell lines in ASC-conditioned medium attenuated ethanol and cerulein-induced pro-inflammatory cytokine production in vitro. Our data show that a single intravenous injection of ASCs ameliorated CP progression, likely by directly differentiating into acinar-like cells and by suppressing inflammation, fibrosis, and pancreatic tissue damage. These results suggest that ASC cell therapy has the potential to be a valuable treatment for patients with pancreatitis.

The objective of this study was to test the hypothesis that distal pancreatectomy (DP) without intraperitoneal drainage does not affect the frequency of grade 2 or higher grade complications.The use of routine intraperitoneal drains during DP is controversial. Prior to this study, no prospective trial focusing on DP without intraperitoneal drainage has been reported.Patients undergoing DP for all causes at 14 high-volume pancreas centers were preoperatively randomized to placement of a drain or no drain. Complications and their severity were tracked for 60 days and mortality for 90 days. The study was powered to detect a 15% positive or negative difference in the rate of grade 2 or higher grade complications. All data were collected prospectively and source documents were reviewed at the coordinating center to confirm completeness and accuracy.A total of 344 patients underwent DP with (N = 174) and without (N = 170) the use of intraperitoneal drainage. There were no differences between cohorts in demographics, comorbidities, pathology, pancreatic duct size, pancreas texture, or operative technique. There was no difference in the rate of grade 2 or higher grade complications (44% vs. 42%, P = 0.80). There was no difference in clinically relevant postoperative pancreatic fistula (18% vs 12%, P = 0.11) or mortality (0% vs 1%, P = 0.24). DP without routine intraperitoneal drainage was associated with a higher incidence of intra-abdominal fluid collection (9% vs 22%, P = 0.0004). There was no difference in the frequency of postoperative imaging, percutaneous drain placement, reoperation, readmission, or quality of life scores.This prospective randomized multicenter trial provides evidence that clinical outcomes are comparable in DP with or without intraperitoneal drainage.

Cholecystectomy after endoscopic sphincterotomy (ES) is associated with improved outcomes compared to ES alone, however randomized trials have included mainly fit surgical candidates. Our objective was to assess the impact of cholecystectomy after ES among elderly patients, in whom the perceived risks of surgery may be increased and the prevailing bias may be to defer cholecystectomy.We performed adjusted analyses comparing clinical outcomes in patients ≥65 years of age who did and did not undergo follow-up cholecystectomy after endoscopic sphincterotomy for choledocholithiasis, ascending cholangitis, or gallstone pancreatitis. We also compared adverse events between the two groups.In the ES alone group, 39.3% of patients experienced a recurrent complication compared with 18.0% in the ES and cholecystectomy group. After adjusting for comorbidities using multivariable regression, cholecystectomy in addition to ES was associated with a reduced risk of recurrent choledocholithiasis (OR 0.38, 95%CI 0.34-0.42, P0.001), ascending cholangitis (OR 0.28, 95%CI 0.23-0.34, P0.001), and gallstone pancreatitis (OR 0.35, 95%CI 0.24-0.49, P0.001) compared to ES alone. This benefit was preserved after propensity score adjustment, in patients ≥75 years of age, and in those with major comorbidities including cancer, heart failure, and liver disease. Serious post-operative complications such as myocardial infarction, pulmonary embolism, and pneumonia were not more common in the cholecystectomy group.Among older patients, including those with serious comorbidities, cholecystectomy after endoscopic sphincterotomy was associated with a significant and clinically important reduction in recurrent complications compared to sphincterotomy alone. This benefit did not appear to be outweighed by surgical complications, highlighting the importance of cholecystectomy, even in elderly patients whose lifespans may be limited by unrelated conditions.

Objective The objective of this study is to assess clinical variables that may be associated with risk for opioid misuse in individuals with chronic pancreatitis. Design This study utilized a descriptive, quasi-experimental, cross sectional design. Setting and Patients Three hundred seven individuals with nonalcoholic chronic pancreatitis engaged in chronic opioid therapy for pain presented to an outpatient specialty clinic at an academic medical center. Measures Participants completed the Current Opioid Misuse Measure (COMM), Brief Pain Inventory (BPI), Short Form (SF)-12 Quality of Life Measure, Center for Epidemiological Studies 10-item Depression Scale (CESD), and a single item asking about current alcohol use. Mean scores on the CESD, COMM, BPI, SF-12, and factors associated with opioid misuse measures from regression analyses were the outcome measures. Results Mean scores on the CESD, COMM, BPI pain-on-average item, and the SF-12 physical and psychological quality of life factors (t scores) were 11.2 (standard deviation [SD] = 6.7), 8.5 (SD = 7.3), 4.8 (SD = 2.8), 39.7 (SD = 7.0), and 45 (SD = 9.0), respectively. Descriptive analyses revealed that 55% of participants scored above the clinical cutoff for depression on the CESD, and 39% scored above the cutoff for opioid misuse concerns on the COMM. Regression analyses identified several factors associated with higher opioid misuse measure scores, including increased depressive symptoms from the CESD (β = 0.38, P

Obesity-induced endoplasmic reticulum (ER) stress causes chronic inflammation in adipose tissue and steatosis in the liver, and eventually leads to insulin resistance and type 2 diabetes (T2D). The goal of this study was to understand the mechanisms by which administration of bilirubin, a powerful antioxidant, reduces hyperglycemia and ameliorates obesity in leptin-receptor-deficient (db/db) and diet-induced obese (DIO) mouse models. db/db or DIO mice were injected with bilirubin or vehicle ip. Blood glucose and body weight were measured. Activation of insulin-signaling pathways, expression of inflammatory cytokines, and ER stress markers were measured in skeletal muscle, adipose tissue, and liver of mice. Bilirubin administration significantly reduced hyperglycemia and increased insulin sensitivity in db/db mice. Bilirubin treatment increased protein kinase B (PKB/Akt) phosphorylation in skeletal muscle and suppressed expression of ER stress markers, including the 78-kDa glucose-regulated protein (GRP78), CCAAT/enhancer-binding protein (C/EBP) homologous protein, X box binding protein (XBP-1), and activating transcription factor 4 in db/db mice. In DIO mice, bilirubin treatment significantly reduced body weight and increased insulin sensitivity. Moreover, bilirubin suppressed macrophage infiltration and proinflammatory cytokine expression, including TNF-α, IL-1β, and monocyte chemoattractant protein-1, in adipose tissue. In liver and adipose tissue of DIO mice, bilirubin ameliorated hepatic steatosis and reduced expression of GRP78 and C/EBP homologous protein. These results demonstrate that bilirubin administration improves hyperglycemia and obesity by increasing insulin sensitivity in both genetically engineered and DIO mice models. Bilirubin or bilirubin-increasing drugs might be useful as an insulin sensitizer for the treatment of obesity-induced insulin resistance and type 2 diabetes based on its profound anti-ER stress and antiinflammatory properties.

The Culture of Peace News Network, an internet news service, is analyzed in the framework of a general approach to education for a culture of peace. Its format reflects the eight program areas for a culture of peace as adopted by the UN General Assembly. Among its other operating principles are universality of news with all cultures and regions of the world given equal priority, requirement that reflection be accompanied by action and that news should be positive and open to debate, that ‘slow news’ is as important as ‘fast news,’ and that readers should participate by writing as well as reading. The Network has yet to achieve its goal of forcing commercial media to consider actions for a culture of peace as newsworthy, but it is suggested that this will depend on the growth of the global movement for a culture of peace which remains rather small at the present time.

Previous studies have shown that total pancreatectomy with islet cell autotransplantation improves quality of life in chronic pancreatitis. A significant number of these patients develop postoperative hyperglycemia and daily insulin requirements or increase in daily insulin requirements. Our study investigates whether increased insulin requirements postoperatively have a negative impact on quality of life. A prospectively collected database of 74 patients undergoing extensive pancreatectomy with islet autotransplantation for pancreatitis was reviewed. Data pertaining to daily requirements and quality of life (QOL), as measured by the SF-12 questionnaire, in the preoperative and postoperative period were reviewed. Approval from the Institutional Review Board for the evaluation of human subjects was obtained. Seventy-four patients underwent extensive pancreatectomy with islet autotransplantation for pancreatitis. The majority of these patients required new daily insulin or an increase in daily insulin requirements post-operatively. Mean preoperative HA1c in this group was 5.6 with an increase to 7.3 at 6 months postoperatively ( P < 0.001), a mean of 8.1 at 12 months, and 8.9 at 2 years. Mean preoperative daily insulin requirements for this group were five units/day with average increase to 19 units/day at 6 months, 21 units/day at 12 months, and 26 units/day at 2 years. Preoperative QOL scores were a mean of 26 for the physical component and 36 for the mental health component. Postoperatively, physical component scores averaged 33 at 6 months (p < 0.001), 36 at 12 months, and 36 at 2 years; the mental health component scores averaged 42 at 6 months (p = 0.007), 41 at 12 months, and 41 at 2 years. There is no correlation between physical component score or mental component score QOL scores and daily insulin requirements ( r = -0.016 and r = 0.039, respectively). Total pancreatectomy with islet cell autotransplantation is an effective surgery for end-stage chronic pancreatitis. Quality of life significantly improves in physical and mental health components regardless of a postoperative increase in daily insulin requirements.

Toll-like receptor 4 (TLR4) activation in pancreatic β cells activates aberrant islet graft cellular pathways and contributes to immune rejection in allogeneic islet transplantation. As an approach to overcoming this problem, we determined the capacity of a 33-amino acid peptide consisting of a protein transduction domain (PTD) from the Hph-1 virus and a fragment of the intracellular domain of TLR4 from the C3H mice (PTD-dnTLR4) to block TLR4 signaling and improve allogeneic islet survival in vitro and after transplantation. The efficacy of PTD-dnTLR4 in blocking TLR4 signaling was assessed in the Raw264.7 macrophage line, in the islets, and the βTC3 cell line. In Raw264.7 cells, preculture with the peptide reduced LPS-induced NF-κB activation and production of proinflammatory cytokines (IL-1β, TNF-α, iNOS, and IL-6). In islets and β cells, preincubation with PTD-dnTLR4 suppressed LPS-induced TNF-α expression via inhibition of NF-κB activation and protected them from stress-induced cell death. In vivo, preincubation of BALB/c (H-2d) islets with PTD-dnTLR4 resulted in significantly longer survival than control islets in a streptozotocin-induced diabetes model (two of seven grafts survived long term >100 days). PTD-dnTLR4-treated grafts exhibited reduced expression of TNF-α and iNOS and reduced macrophage infiltration posttransplant. The data indicate that PTD-dnTLR4 blocked TLR4 signaling in both macrophages and β cells, and prolonged allograft survival at least in part by suppressing inflammation and macrophage infiltration. This strategy for blocking TLR4 activity has potential utilization in the treatment of diseases where excessive TLR4 activation contributes to the pathologic cellular pathways such as islet transplantation.

The Puestow procedure, also called lateral pancreaticojejunostomy, has been the mainstay of surgical therapy for dilated duct chronic pancreatitis for decades. Principles that Puestow and Gillesby described in 1958 are pertinent to the modern conduct of this operation that is described with current practice guidelines.

Total pancreatectomy with immediate islet autotransplantation (IAT) can be an effective therapy in patients with chronic pancreatitis. Patient selection criteria for radical resection are not well defined. The impact of prior pancreatic surgery on quality of life outcomes in patients undergoing IAT is evaluated. A retrospective review of a prospectively collected database of patients undergoing pancreatectomy with islet autotransplantation was undertaken. Patients having undergone prior pancreatic resection and/or drainage procedures were compared with those without prior pancreatic operative history. Sixty-one patients underwent pancreatectomy with IAT for pancreatitis. Twenty-three patients had a prior history of pancreatic surgery (Group S); 38 had no prior history of pancreatic surgery (Group NS). Demographics between the groups were similar. Patients in Group S took more daily oral morphine equivalents and had a lower psychological quality of life preoperatively. Operative times and blood loss were similar between the patient groups. Islet yields were lower for patients in Group S. Postoperatively, daily insulin requirements at 6 months and 1 year trended higher in Group S. Postoperative quality of life scores at 6 months were improved and similar between the groups. Quality of life metrics continued to improve beyond 1 year of follow-up, with a trend toward greater improvement in the NS Group. Total pancreatectomy for chronic pancreatitis improves quality of life in patients with and without a prior history of pancreatic surgery. This study demonstrates that IAT without preceding pancreatic surgery may enhance outcomes measured by long term insulin requirements and quality of life.

In selected patients with chronic pancreatitis, total pancreatectomy with islet autotransplantation can be effective for the treatment of intractable pain while ameliorating postoperative diabetes. Improved quality of life scores and decreased daily narcotic use, as indicators of successful pain relief, are expected after total pancreatectomy. These outcomes and their relationship have not been well examined in this patient group. A prospectively collected database of patients undergoing extensive pancreatectomy with islet autotransplantation for pancreatitis was reviewed. Data pertaining to daily oral morphine equivalents (MEs) and quality of life (QOL), as measured by the SF-12 questionnaire, in the preoperative and postoperative period were reviewed. Approval from the IRB for the evaluation of human subjects was obtained. Over a 20-month period, 33 patients (25 women, median age 42) underwent extensive pancreatectomy with islet autotransplantation for pancreatitis. Mean follow-up was 9 months with a range of 6–12 months. Postoperative complications occurred in 16 patients (48%). Preoperative QOL scores were a mean 25 for physical component and 32 for mental health component. Postoperatively, physical component scores averaged 33 at 6 months (p = 0.025) and 36 at 12 months (mean increase of 11); the mental health component scores averaged 43 at 6 months (p = 0.007) and 44 at 12 months (mean increase of 12). Preoperative MEs averaged 357 mg daily. At discharge from the hospital, this number increased to 536 mg average MEs daily, a 50% increase, as expected after major surgery in the chronic pain patient. At 6 months, 15 out of 31 patients (48%) required less daily MEs than preoperatively and averaged 161 mg daily (−55%). By 12 months, 11 out of 17 patients (65%) required less daily MEs than preoperatively and averaged 128 mg daily (−64%); four were narcotic-free (23%). Of the six patients who did not decrease their analgesic requirements at 1 year, five (83%) still had an improved physical QOL score (one patient was unchanged) and all six had an improved mental health QOL. Total pancreatectomy with islet autotransplant is an effective surgery for end-stage chronic pancreatitis. Quality of life improves early postoperatively while decreased narcotic analgesia requirements occur later. Both improved quality of life and decreased narcotic analgesia requirements continue to occur at least up to 1 year postoperatively. Further investigation is needed to assess the durability of total pancreatectomy with islet autotransplantation for severe chronic pancreatitis with respect to pain relief and improved quality of life.

Laparoscopic cholecystectomy (LC) has served as the igniting spark in the laparoscopic surgery explosion; however, it is unclear who created the spark. The question remains: Who did the first LC?

Background and Aims ERCP has largely replaced common bile duct exploration for therapy of common bile duct pathology, yet its use as a purely diagnostic test has declined. Among inpatients, we hypothesized that timing between ERCP and cholecystectomy (CCY) has changed. The objectives were to measure temporal trends in the timing between inpatient ERCP and CCY and to examine factors associated with delays. Methods We used the National Inpatient Sample between 1998 and 2013 to classify admissions for gallstone-related diagnoses undergoing inpatient CCY and ERCP by timing relative to CCY: within (±) 1 day, ≥2 days before, and ≥2 days after. Logistic regression and Poisson regression were used to determine pattern utilization and association of ERCP timing on hospital length of stay. Results Between 1998 and 2013, the proportion of admissions for CCY associated with same-stay ERCP increased (14.5% in 1998 to 17.3% in 2013, P Conclusions Use of inpatient ERCP in conjunction with CCY has increased minimally between 1998 and 2013, whereas length of stay has decreased. ERCPs performed within 1 day of CCY were associated with shorter hospital length of stay, suggesting delays between inpatient procedures should be minimized unless medical comorbidities preclude it.

Cystic lesions of the pancreas are identified with increasing frequency by modern imaging. The mucinous cystic neoplasm (MCN) is treated with resection for its malignant potential. How much preoperative evaluation is needed before undertaking operation is frequently a diagnostic dilemma. A retrospective review of 32 patients who underwent resection of a MCN between 1994 and 2007 was performed to define the preoperative evaluation and operative treatment of MCN patients. Thirty-two patients (30 women; mean age 49) had histology-proven MCN. Twenty-seven patients had symptomatic cysts (84%). Five had a history of gallstones and/or acute pancreatitis. All patients were worked up with CT and/or MRI. Endoscopic ultrasound was performed in 14 (44%) and endoscopic retrograde cholangiopancreatography in six (18%). Cytology was obtained in 13 (40%). Pathology revealed 22 benign MCNs (68%), five malignant MCNs (16%), and five MCNs with borderline pathology. Preoperative workup including CT or MRI imaging and cytology suggested MCN as the lesion in 15 patients (46%). CT features by itself predicted MCN in three patients (9%). Cytology revealed another six patients (19%) with possible MCN. In this series, preoperative workup did not identify three of five patients with MCN malignancy. A preoperative diagnosis cannot be made in most patients with MCN. Operative treatment can be based on clinical presentation and CT imaging because endoscopic ultrasound and fine needle aspiration for evaluation may be misleading. Middle-aged women with cystic lesions in the tail of the pancreas without prior gallstone or pancreatitis history most typically fit the profile of the MCN patient.

Pancreatic pseudocysts represent the majority of cystic lesions, and can usually be differentiated from cystic neoplasms, which have malignant potential. Endoscopic retrograde cholangiopancreatography (ERCP) can help in solving diagnostic dilemmas. When ERCP demonstrates cyst communication with the pancreatic duct, the diagnosis of pseudocyst is usually secure. There are exceptions, however, as reported in these two case reports. A retrospective chart review was conducted of two patients undergoing distal pancreatectomy in 2008 to 2009 for cystic lesions communicating with the main pancreatic duct on ERCP. Both patients were women (ages 37 and 42) with a history of chronic abdominal pain and pancreatitis. Radiologic imaging showed cystic lesions in the pancreatic tail. ERCP demonstrated main pancreatic duct communication. When endoscopic management failed, surgical therapy was undertaken. Both patients underwent distal pancreatectomy with splenectomy. Pathologic findings were mucinous cystadenoma. The conventional wisdom that a pancreatic cyst communicating with the main pancreatic duct is a benign pseudocyst is not always wise. As seen in this series, mucinous cystadenomas can erode into the main pancreatic duct. Women in the fourth and fifth decade with symptomatic cysts in the pancreatic tail with a history of pancreatitis should undergo distal pancreatectomy, regardless of ductal communication on ERCP.