French policymakers recently chose to regulate high-risk digestive cancer surgery (DCS). A minimum of five cases per year should be performed for each of the following types of curative cancer surgery: esophagus/esogastric junction (ECS), stomach (GCS), liver (LCS, metastasis included), pancreas (PCS), and rectum (RCS). This study aimed to evaluate the hypothetical beneficial effects of the new legal minimal volume thresholds on the rates of 90-day postoperative mortality (90POM) for each high-risk DCS. This nationwide observational population-based cohort study used data extracted from the French National Health Insurance Database from 1 January 2015-31 December 2017. Mixed-effects logistic regression models were performed to estimate the independent effect of hospital volume. During the study period, 61,169 patients (57.1 % male, age 69.7 ±12.2 years) underwent high-risk DCS including ECS (n = 4060), GCS (n = 5572), PCS (n = 8598), LCS (n = 10,988), and RCS (n = 31,951), with 90POM of 6.6 %, 6.9 %, 6.0 %, 5.2 %, and 2.9 %, respectively. For hospitals fulfilling the new criteria, 90POM was lower after adjustment only for LCS (odds ratio [OR],15.2; 95 % confidence interval [CI], 9.5-23.2) vs OR, 7.6; 95 % CI, 5.2-11.0; p < 0.0001) and PCS (OR, 3.6; 95 % CI, 1.7-7.6 vs OR, 2.1; 95 % CI, 1.0-4.4; p<0.0001). With higher thresholds, all DCSs showed a lower adjusted risk of 90POM (e.g., OR, 0.38; 95 % CI, 0.28-0.51) for PCS of 40 or higher. Based on retrospective data, thresholds higher than those promulgated would better improve the safety of high-risk DCS. New policies aiming to further centralize high-risk DCS should be considered, associated with a clear clinical pathway of care for patients to improve accessibility to complex health care in France.

Impact of removing donation service area and region from pancreas allocation

Uganda has until recently mostly referred patients for complex hepato-pancreato-biliary (HPB) surgery abroad due to lack of local expertize. We report indications and a spectrum of surgeries performed in the first 4years following the establishment of a routine HPB service at Lubaga Hospital (LH), Kampala, Uganda. We also detailed the challenges encountered in setting up this service. Demographic, clinical parameters, surgery indications, procedures performed, and outcomes of consecutive patients that underwent HPB surgeries at LH from December 2018 to October 2022 were analyzed. Majority were females 72 (57.6%) with a median age of 50 (6-88) years. Forty-one (32.8%) underwent surgery on the pancreas (PS), 34 (27.2%) on the liver (LS), and 50 (40.0%) on the bile ducts (CBS). The most common symptom was abdominal pain. Benign disease was present in 37 patients (29.6%) while 88 (70.4%) had malignancy. A total of 34 patients (27.2%) had unresectable pancreatic head cancer and distal cholangiocarcinoma missed at preoperative imaging and discovered intraoperatively thus underwent palliative hepaticojejunostomy. Only 34 (27.2%) patients received postoperative ICU care. In-hospital mortality for this heterogenous group of patients was 6 (4.8%) for PS, 3 (2.4%) for LS, and 8 (6.4%) for CBS. Despite many challenges like limited access to ERCP accessories, lack of endoscopic ultrasound scans and PET-CT scans in the whole country, late presentation, and low quality imaging especially in preoperative determination of resectability of hepato-pancreato-biliary cancers, we managed to establish a functional HPB service. Patient results achieved were good in spite of these limitations.

Abstract Disclosure: S. rafiqi: None. Z. Zahid: None. R. Lamendella: None. O. aghogho: None. E. Gionfriddo: None. Y. Tao: None. J.C. Jaume: None. S. Imam: None. The infant gut microbiome essentially shifts to a diverse and complex microbial system during weaning on separation from the mother and any perturbations lead to pathological imprinting with lifelong implications. Apart from breast milk, the microbiota of the skin and the intimate niche between mother and offspring contribute to gut microbial composition. Gut microbiome dysbiosis has been ascribed in the initiation and/or perpetuation of type 1 diabetes (T1D) in human and animal models. The gut microbial diversification is manifested as change in microbial metabolites particularly short-chain fatty acids (SCFAs) that have direct and indirect roles in immune regulation and epithelial barrier integrity. In this study, we try to decipher the role of prolonged nursing of newborn mice (upto 45 days) in the amelioration of type 1 diabetes in the context of changes in the gut microbiome and microbial metabolites. The humanized T1D mice used in the study spontaneously develop T1D at 3-4 weeks of age and are normally weaned at 21 days. Our results revealed mice subjected to prolonged nursing had consistent increments in levels of butyric acid from 60 to 150 days of age as compared to normal weaned mice, owing to a stable population of SCFA-producing bacteria developed during prolonged nursing with the mother. The normal weaned mice had a transient increase of butyric acid at 60 days but it didn’t sustain till the 150th day. The steady levels of butyrate in prolonged nursed mice exerted immunoregulatory roles which manifested in the enrichment of regulatory T cells (Tregs) in the intestinal mesenteric epithelium, payer’s patches, peri pancreatic lymph nodes (PLN), pancreas (PN) and spleen. The enrichment of Tregs leads to the regulation of diabetogenic Th1, Th17, and interferon gamma-producing CD8 T cells (cytotoxic lymphocytes, CTLs) at PLN, PN, and spleen. This increased immune tolerance was mirrored by improved glucose homeostasis and fasting blood glucose levels in the prolonged nursing group. Prolonged nursing preserved the pancreatic islet architecture and significantly maintained the increased number of islets per pancreas as observed in H&amp;E sections. Also, it could be inferred from the results that SCFA’s promoted intestinal integrity with increased submucosal thickening, longer villi, and shallower crypts in the intestine of prolonged nursed mice. In conclusion, prolonged nursing accounts for gradual and steady gut microbiota succession in infants that augments SCFA production leading to enrichment of T regulatory cells and less aggressive diabetes. Presentation: Saturday, June 17, 2023

IntroductionResveratrol and related polyphenols have therapeutic effects ranging from treatment of depression, Alzheimer's and Parkinson's disease, obesity, diabetes, neurodegeneration and ageing. TRH and TRH‐like peptides, with the structure pGlu‐X‐Pro‐NH2, where ‘X can be any amino acid reside, have reproductive, caloric‐restriction‐like, anti‐ageing, pancreatic‐β cell‐enhancing, cardiovascular and neuroprotective effects. We hypothesize that TRH and TRH‐like peptides are mediators of the therapeutic actions of the resveratrol derivative pterostilbene (PT).MethodsSixteen young adult male Sprague–Dawley rats were divided into four groups. Control group remained on ad libitum chow and water for 10 days. Acute group received ad libitum chow and water for 9 days and then 0.9 g PT/250 g rat chow for 24 h. Chronic animals received PT in chow for 10 days. Withdrawal rats received PT chow for 8 days and then normal chow for 2 days. TRH and TRH‐like peptide levels were measured in medulla oblongata (MED), frontal cortex (FCX), hypothalamus (HY), amygdala (AY), hippocampus (HC), piriform cortex (PIR), nucleus accumbens (NA), entorhinal cortex (ENT), striatum (STR), cerebellum (CBL), anterior cingulate (ACNG), posterior cingulate (PCNG), prostate (PR), liver (L), testis (T), heart (H), pancreas (PAN), adrenals (AD) and epididymis (EP).ResultsSignificant changes in the levels of TRH and TRH‐like peptides occurred throughout the brain and peripheral tissues in response to PT treatment.ConclusionThe high responsiveness of PIR, CBL, HY, STR, PCNG, MED, FCX, NA, ACNG and AY in brain and EP and PR is consistent with TRH and TRH‐like peptides participating in the therapeutic effects of PT.

563 Background: RUB is an oral PARP1,2,3 inhibitor that demonstrated efficacy in patients (pts) with ovarian and prostate cancers harboring deleterious BRCA mutations. RUB exerts synergistic anti-tumor effect with IRI preclinically though the combination has overlapping toxicities. We previously published on the population PK of nal-IRI (Adiwijaya, Ma et al, Clin Pharm Ther 2017). We conducted a phase I study to evaluate a novel sequential dosing of RUB with nal-IRI/5FU in mGI cancer pts. Methods: Eligible pts had incurable mGI cancer previously received &gt; 1 line of therapy (rx), ECOG PS 0-1, had RECIST measurable disease, adequate organ reserves and not received IRI for metastatic disease. Previous PARPi rx was excluded. The endpoints included dose limiting toxicity (DLT), maximum tolerated dose (MTD) and toxicity profile. The dose escalation utilized the 3+3 design. RUB was given oral bid on Day 4 to 13 and 18 to 27 with nal-IRI i.v. and 5FU i.v. 2400 mg/m2 over 46 hr on Day 1 and 15, every 28 day. Planned dose levels were RUB 400 mg/nal-IRI 50 mg/m2 (DL1), 400 mg/70 mg/m2 (DL2) and 600 mg/70 mg/m2 (DL3). Adverse events (AEs) were scored per CTCAE v4.03. Molecular profile was evaluated by CLIA-certified NGS testing. Results: Eighteen pts including 11 colorectal (CRC), 6 PANC, 1 gastroesophageal (GE) were enrolled and 12 were evaluable for DLTs. DL2 was not tolerable (DLT: G3 diarrhea, nausea and vomiting) and DL2A was added (RUB 600 mg/nal-IRI 50 mg/m2). DL2A enrolled 6 pts with no DLT and was determined as the MTD. Of DLT-evaluable pts, G3 and worse treatment-related AEs from all cycles were diarrhea (33%), fatigue (25%), leukopenia (25%), neutropenia (25%), anemia (8%) and nausea (8%). Four of 12 response evaluable pts had partial response: 2 CRC (1 had ATM mut), 1 PANC ( ATM mut), 1 GE ( BRCA2 mut) whilst 3 responders previously had platinum (PLA). Five pts had stable disease beyond 16 weeks (range 18.9 to 100.7 weeks), and all had prior PLA. Conclusions: The study successfully determined the MTD of RUB in combination with nal-IRI and 5FU. Encouraging efficacy was observed in PLA-treated mGI cancers including responses in those harboring ATM and BRCA alterations. The study is proceeding to evaluate the efficacy of the combination in metastatic pancreas cancer pts with and without BRCA1/2 or PALB2 alterations. Clinical trial information: NCT03337087.

Introduction: Pancreatic Transplant (PTX) is a safe surgical procedure offered to diabetic patients with or without chronic kidney disease. With the new allocation system in the US, more pancreas offers are coming from beyond one’s donor service area (DSA), and region. Whether transplanting grafts from beyond one’s DSA or region is a safe practice is unknown. In this study, we analyzed our experience with importing pancreata according to DSA and UNOS region source and distance from the donor hospital to the transplant center, resembling the newest changes mandated by UNOS allocation policies. Methods: We analyzed primary PTXs performed between January 2000 and December 2018. Recipients of simultaneous pancreas and kidney (SPK), primary solitary pancreas (PAN) including pancreas after kidney (PAK) and pancreas transplant alone (PTA) transplants were analyzed. Two separate analyses were performed: i) based on graft origin (local, regional and national) and ii) based on nautical mile (NM) distances form the (< 250 NM, 250 and 750 NM and > 750 NM) which were retrospectively determined. Primary outcome was DC-graft survival (DC-GS), overall and stratified by transplant type and geographical source. DC-GS survival was analyzed using Kaplan-Meier analyses. All grafts were enterically drained with systemic venous drainage. Results: There were 884 PTXs; 676 underwent SPK and 208 PAN. Of these, 152 underwent PTA and 56 PAK. Donor PDRI and recipient baseline characteristics were similar between groups. Evaluating all PTX together, we observed no statistical differences in the DC-GS based on local, regional or national organ source; nor did we see a difference based on NM distance. Analyzing by graft origin (local vs regional vs national): the 5-year DC-GS rates for SPK were similar at 83% vs 83% vs 85% (p=0.50) and the 5-year DC-GS rates for PAN were 82% vs 64% vs 75% (p=0.17). The 5-year DC-GS rates were also similar across locales for both PTA (83% vs 60% vs 77%; p=0.14) and PAK (78% vs 73% vs 69%; p=0.55). Based on the NM distance from donor to transplant hospital (<250NM, 250-750NM and >750NM): the 5-year DC-GS rates for SPK were similar across distances at 83% vs 84% vs 89% (p=0.69). The 5-year DC-GS rates for PAN were not different from one another at 73% vs 72% vs 78% (p=0.96). The 5-year DC-GS rates across distances for PTA (71% vs 73% vs 81%; p=0.79) and PAK (76% vs 70% vs 67%; p=0.65) were not statistically different from one another. Conclusions: With greater sharing mandated by new UNOS allocation policies, we aim to demonstrate the utility of importing selected pancreata from non-local regions and DSAs and from > 250NM from the transplant center. This experience emphasizes the possibility of importing pancreatic grafts to increase organ utilization, increase center transplant rates and reduce waiting times for patients.

Актуальність. Неалкогольна жирова хвороба печінки (НАЖХП) є самостійною нозологічною одиницею, характеризується накопиченням жиру в гепатоцитах, не пов’язаним зі зловживанням алкоголем, і включає широкий спектр порушень — від жирової дистрофії печінки, неалкогольного стеатогепатиту до фіброзу з можливим переходом у цироз печінки. З огляду на поширеність цієї патології, погіршення якості життя хворих, збільшення смертності від ускладнень зростає інтерес до розробки методів для точної й своєчасної оцінки фіброзу. Мета: порівняльна характеристика результатів транзієнтної еластометрії (FibroScan) і неінвазивних лабораторних індексів у визначенні фіброзної трансформації печінки у хворих із неалкогольною жировою хворобою печінки. Матеріали та методи. У дослідження включені пацієнти з НАЖХП, які проходили обстеження й лікування у відділенні захворювань печінки та підшлункової залози ДУ «Інститут гастроентерології НАМН України». Обстежені 42 пацієнти з НАЖХП, серед яких 18 (45 %) чоловіків і 24 (55 %) жінки. Усім пацієнтам було виконано розрахунок неінвазивних маркерів фіброзу печінки: APRI, FIB­4, співвідношення аланінамінотрансферази/аспартатамінотрансферази, проведено вимірювання жорсткості печінки за допомогою апарату FibroScan. Результати нашої роботи узгоджуються з більшістю досліджень, згідно з якими найбільш ефективним з малоінвазивних індексів є APRI. Висновки. Поєднання транзієнтної еластометрії (FibroScan) з індексом APRI може забезпечити більш ефективний підхід до діагностики фіброзу печінки у хворих з НАЖХП.

Background: The current study aimed to determine the trends in esophageal cancer (EC) patients and examine the impact of the type and anatomical location of the tumor and the site of metastasis on their survival. Method: In this retrospective cohort study, we investigated 305 patients with a definitediagnoses of EC, who had been hospitalized at the Mahdie Hospital of Hamadan, Iran, during ten years from 2005-2015. EC-related survival considering different types and locations of the tumor, as well as the sites of metastasis, was evaluated. Survival was calculated using Kaplan-Meier curves and a multivariable Cox regression analysis (MVA) was performed. Results: Squamous cell carcinoma was found in 76.6% of the patients, and 23.4% had adenocarcinoma (AC). There was a significant relationship between the location and pathological type of tumor; 87% of ACs happened in the lower part of the esophagus (P=0.015). The 1 to 5-year relative survival of the patients was 46%, 25%, 22%, 12%, and 7%, respectively. The rate of death in liver, lung, brain, pancreas, abdomen, and lymph nodes metastasis were respectively 42.9%, 21.4%, 14.3%, 7.1%, 7.1%, and 7.1%. No significant relationships were observed between the tumor type and metastasis (P=0.14) or between the tumor type and the location of metastasis (P=0.7). Conclusion: Similar to other reports, the rate of survival was higher in AC type, yet the rate of total survival in Iran was much lower than that in developed countries. There were no differences in the survival rate concerning the location of the tumor. The obrained results did not show any relationships among the tumor type, the location of metastasis, and the total survival.

An antibody joins forces with the pancreas to delay diabetes

Immunoglobulin G4 related-disease (IgG4-RD) is a multisystemic immune-mediated fibroinflammatory disease, with a strong predilection for salivary and lacrimal glands, pancreas, biliary tree, lungs, kidneys, aorta, and retroperitoneum. In the case of pancreatic involvement, it manifests as autoimmune pancreatitis. Patients with IgG4-RD usually have mild to moderate eosinophilia in the peripheral blood, however, they may present a secondary hypereosinophilic syndrome (HES). Although there are cases described with severe eosinophilia (> 5,000/µL), the 2019 American College of Rheumatology/European League Against Rheumatism classification criteria for IgG4-RD considers peripheral eosinophilia above 3,000/µL as an exclusion criterion, although stating that assessment for the presence of exclusion criteria should be individualized depending on a patient’s clinical scenario. Here, we describe the clinical case of a 30-year-old woman who presented with chronic diarrhea and abdominal pain. The diagnostic workup revealed eosinophilic ascites, severe peripheral blood eosinophilia (> 5,000/µL), IgG4 elevation (> 2 × upper normal limit), and also diffuse swelling in the body and pancreatic tail (computed tomography (CT) scan). There was a prompt response to corticosteroid therapy with clinical resolution and continued remission under therapy. The patient was diagnosed with IgG4-RD with secondary HES, explaining the gastrointestinal tract and peritoneum damage in the form of enterocolitis and ascites. Exclusion of alternative diagnosis was made. J Med Cases. 2021;12(3):107-111 doi: https://doi.org/10.14740/jmc3634

Workers of the Commissariat for Atomic Energy and Alternative Energy (CEA) may be potentially exposed to tritium over long periods. We aimed to assess the effect of tritium exposure on mortality in a cohort of employees followed by radiotoxicological monitoring. A total of 1,746 employees who worked for at least six months at one of three CEA centers were included between 1962 and 2011 (median follow-up 29.6 years). The cumulative dose of tritium was based on the quantification of tritium present from urinary excretion monitoring data from the beginning of occupational exposure to the end of such exposure or December 2011. Mortality was first compared to that in the French population using the standardized mortality ratio (SMR). Then, mortality risk ratios (RRs) per category of cumulative dose of tritium were estimated using categorical Poisson models adjusted for age at the onset of exposure, age, calendar period, sex, smoking, employment status, CEA center, and taking into account the number of person-years. The main causes of mortality were tumors (48%) and cardiovascular diseases (20%). The comparison of mortality within the cohort to that in the French population highlighted a lower rate for all-cause mortality and that due to cancer, related to the healthy worker effect bias. The regression model showed no effect of cumulative dose on all-cause mortality. The risk of death for most malignancies was positive, but not significant for the higher classes of doses relative to the reference class. The highest risk (not significant) was present for the class of higher doses for tumors of the larynx, trachea, bronchi and lung. The risk was significant for the higher doses for tumors of the pancreas and bladder (based on a limited number of cases: five and six deaths, respectively). Significantly more smokers died from tumors of the respiratory system than non-smokers, as expected. We were unable to show an effect of cumulative tritium dose due to the small size of the cohort and the low exposure level. However, our study underlines the need to continue following tritium-exposed workers and conducting multicenter studies.

Background: Methamphetamine (METH) is a widely addictive and abused psychostimulant drug that affects organs of body. In this study, the effects of METH administration for 7, 14, and 28 days on the histological and functional changes of the liver and pancreas of adult male rats were investigated. Methods: In this experimental study, 58 adult male Wistar rats were randomly divided into seven groups including control (received no treatment), vehicle (received saline for 7, 14, and 28 days), and METH (received METH with a dose of 5 ml/kg, IP for 7, 14 or 28 days). Sampling from the liver and pancreas tissues was done after the above-mentioned times for each group, then, tissue samples were stained by H&E technique and evaluated for structural changes, as well as the evaluation of biochemical factors including SGPT, SGOT, and amylase enzymes. Data were analyzed by one-way ANOVA, using SPSS software version 20. Statistical significant level was considered at p <0.05. Results: In this study, METH caused a significant structural change in the liver and pancreas in the METH-treated groups compared with the control group. Functional changes depended on the length of treatment, with the 7-day treatment group having less damage than the 14- and 28-day periods. Conclusion: According to the results of the present study, methamphetamine administration for 7, 14, and 28 days had adverse effects on the rats liver and pancreas structure and their enzymes (SGPT, SGOT, and amylase). Therefore, underlying mechanism need further investigation.

Several medicinal plants have anti-diabetic properties and can be considered as an alternative therapy because of their actions which are like those of conventional antidiabetic drugs. In this study, we investigated Myrothamnus flabellifolius (MF) ethanol: water (70:30) extract for its possible anti-diabetic potential in streptozotocin-high energy diet (STZ-HED) induced type 2 diabetes mellitus (T2DM) rats and its possible mechanisms of action. Diabetic rats were divided into MF-50, MF-100, MF200, MF-300, MF-400, and Metformin (MET)-500 groups, where the numbers represent doses in mg.kg.bw that were administered to the groups. Normal (NC) and diabetic (DC) controls were administered distilled water. The animals had their fasting blood glucose levels and body weights determined weekly for 21 days. Blood samples, liver, pancreas, and muscle were collected and used for biochemical and histological examination. Our study showed that MF extract lowered glucose levels, body weight, glycated hemoglobin, thiobarbituric acid reactive substances, serum glutamate pyruvate transaminase, serum glutamate oxaloacetate transaminase, Homeostatic model assessment of insulin resistance, and alkaline phosphatase (p<0.05; p<0.01) in T2DM. While adiponectin, catalase, leptin, lipid profile, insulin Homeostatic model of assessment of β cell function, and superoxide dismutase levels were elevated (p<0.05; p<0.01). Furthermore, MF extract preserved both the liver and the islets structure of T2DM rats and enhanced muscle glucose transporter 4 (GLUT 4) expression. M. flabellifolius extract normalized blood glucose and body weight in T2DM. Further investigations are needed to explore other possible mechanisms of action and clinical potential of MF extracts. Key words: Myrothamnus flabellifolius, T2DM, Lipid profile, blood glucose, oxidative stress, streptozotocin-high energy diet, Sprague dawley rats.

Amaç: Çalışmada bisfenol A (BPA)'ya maruz bırakılan sıçanların pankreasındaki değişikliklerin belirlenmesi ve bu değişiklikler üzerine koenzim Q10 (KoQ10)'un etkilerinin ortaya çıkarılması amaçlandı.Materyal ve metod: Sıçanlar kontrol, sham, KoQ10, BPA ve KoQ10+BPA olmak üzere rastgele beş gruba ayrıldı. KoQ10 ve BPA uygulamaları on dört gün boyunca devam etti. Histopatolojik ve histomorfolojik incelemeler için pankreas kesitlerine Crossmon’un üçlü boyama yöntemi uygulandı. Ayrıca pankreas dokusunda immünohistokimyasal olarak östrojen reseptör α (ERα) immünoreaktivitesi incelendi.Bulgular: Pankreasın endokrin bölümündeki histopatolojik değişiklikler ile pankreatik beta hücrelerindeki ERα immünoreaktivitesinin kontrol grubuna göre BPA grubunda anlamlı bir şekilde arttığı tespit edildi. Ancak histomorfolojik bulgular açısından gruplar arasında anlamlı bir fark bulunmadı. Diğer taraftan, çalışmada incelenen parametreler üzerinde KoQ10'un anlamlı bir etkisi gözlenmedi.Sonuç: BPA, pankreasta yapısal ve fonksiyonel bozukluklara neden olabilir. Ayrıca ERα immünoreaktivitesini de değiştirebilir. Bununla birlikte, KoQ10'un BPA'ya maruz kalan sıçanların pankreasındaki muhtemel koruyucu etkilerini ortaya çıkarmak için daha ileri çalışmalar gereklidir.

An erratum was issued for:Detergent-Free Decellularization of the Human Pancreas for Soluble Extracellular Matrix (ECM) Production. The author list was updated. The author list was updated from: Riccardo Tamburrini1,2,3, Deborah Chaimov1,3, Amish Asthana1,3,Kevin Enck3, Sean M. Muir4, Justine Mariam Aziz5, Sandrine Lablanche6, Emily Tubbs6, Alice A. Tomei7,8, Mark Van Dyke9, Shay Soker3, Emmanuel C. Opara3, Giuseppe Orlando1,3 1Department of Surgery, Wake Forest Baptist Medical Center, 2Department of General Surgery, PhD Program in Experimental Medicine, University of Pavia, 3Wake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine, 4Wake Forest University College of Arts and Science, 5Wake Forest University School of Medicine, 6Laboratory of Fundamental and Applied Bioenergetics (LBFA), and Environmental and System Biology (BEeSy), Grenoble Alps University, 7Department of Biomedical Engineering, University of Miami, 8Diabetes Research Institute, University of Miami Miller School of Medicine, 9Department of Biomedical Engineering and Mechanics, School of Biomedical Engineering and Sciences, Virginia Polytechnic Institute and State University to: Riccardo Tamburrini1,2,3, Deborah Chaimov1,3, Amish Asthana1,3,Carlo Gazia3,4,Kevin Enck3, Sean M. Muir5, Justine Mariam Aziz6, Sandrine Lablanche7, Emily Tubbs7, Alice A. Tomei8,9, Mark Van Dyke10, Shay Soker3, Emmanuel C. Opara3, Giuseppe Orlando1,3 1Department of Surgery, Wake Forest Baptist Medical Center, 2Department of General Surgery, PhD Program in Experimental Medicine, University of Pavia, 3Wake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine, 4Department of Surgery, Tor Vergata University of Rome 5Wake Forest University College of Arts and Science, 6Wake Forest University School of Medicine, 7Laboratory of Fundamental and Applied Bioenergetics (LBFA), and Environmental and System Biology (BEeSy), Grenoble Alps University, 8Department of Biomedical Engineering, University of Miami, 9Diabetes Research Institute, University of Miami Miller School of Medicine, ​10Department of Biomedical Engineering and Mechanics, School of Biomedical Engineering and Sciences, Virginia Polytechnic Institute and State University.

Introduction: Paragangliomas and pheochromocytomas are rare neuroendocrine tumors, indistinguishable at the cellular level, from chromaffin cells derived from the neural crest. The term paraganglioma refers to extra-adrenal tumors and pheochromocytoma to intra-adrenal tumors. Parasympathetic paragangliomas are located along the glossopharyngeal and vagal nerves of the neck and at the basis of the skull and generally do not secrete catecholamines. Sympathetic tumors, on the other hand, are located in the sympathetic paravertebral ganglia of the chest, abdomen and pelvis, and produce excess catecholamines, which induce a clinical history of severe hypertension, headache and tachycardia. Most sympathetic paragangliomas are familial, associated with mutations in the SDHD and SDHB genes, which the last one have a higher risk of malignancy, being necessary to search for metastatic lesions as part of the preoperative evaluation. Malignant paragangliomas are a rarer form of presentation and patients should be followed up on an outpatient basis for a long term due to the risk of metastases, which usually affect bones, lungs and liver. Objective: To report a case of a patient diagnosed with malignant paraganglioma who presented metastases 4 years after the diagnosis and surgical removal of his tumors. Case report: VM, male, a 59-year-old man comes to the health unit with a previous diagnosis of hypertension, using beta-blocker, angiotensine receptor antagonist and diuretic, complaining of difficulty in control disease and recurrent headache. Dyslipidemic, using simvastatin, social drinker, denies smoking and other pathologies. Tests were requested to investigate secondary causes, including abdominal ultrasound showing mass in retroperitoneum. Imaging investigation proceeded with abdominal computed tomography (CT) indicating a heterogeneous mass of regular contours measuring 10.9 x 9.9 x 8.3 cm with areas of cystic degeneration and contrast enhancement, in the topography of the head/uncinate process of the pancreas exerting slight compression on the inferior vena cava. The anatomopathological study after attempting surgical resection showed paraganglioma. He started alpha and beta-blockers due to a hypertensive peak in the first approach undergoing a new surgery after 21 days for complete resection of the tumor and histopathology that found malignant pheochromocytoma. He followed an outpatient follow-up showing improvement of symptoms. After 4 years without signs of recurrence, he had a CT scan of the liver showing at least 6 nodular images with characteristics of secondary involvement. He returned to oncology to investigate the new injuries and is awaiting liver biopsy and/or metastasectomy. Keywords: Malignant paraganglioma; Neuroendocrine tumors; Paraganglioma.

Gestational diabetes mellitus (GDM) used to be defined as any degree of glucose intolerance with onset or first recognition during pregnancy. Gestational Diabetes Mellitus (GDM) is the most common metabolic disorder during pregnancy. It is associated with maternal and fetal complications. Screening for GDM and its risk factors is essential for the early diagnosis and management. Recently, the definition has evolved to distinguish women whose condition is a transient manifestation of pregnancy-related insulin resistance from those with probable preexisting diabetes that is first recognized during pregnancy. The physiological and hormonal change during pregnancy can lead to increase insulin resistance and production of glucose, if pancreas cannot secrete sufficient insulin to maintain blood glucose can cause impaired glucose tolerance or gestational diabetes. Aim of the study: This study aimed to evaluate the prevalence of GDM among pregnant women's in the obstetric clinics in MCH at Makkah city. Methodology: analytic cross sectional study was conducted among (147) pregnant women who attend obstetric clinics in the one-month using the simple has been random technique using random table generator. Maternal and children's hospital is the biggest hospital in Makkah and has 3 clinic per day. Results: A total of (170) participated in the study. Regarding age of these Only(46.5%)of the participated were(>35)years, the weight(current) the data ranged from(40to136)by mean +SD(72.905±16.167). While the weight before pregnancy the data ranged from (39to1727)by mean +SD(67.985±15.082). The age a significant relation between diabetic mellitus and age were P-value=0.001and X2(8.860) increase in >35years answer YES were(71.4%). Gravida show a significant relation between diabetic mellitus were P-value=0.036 and X2(10.255) increase in more than 4 answer YES were (57.1%). the gravida/para/abortus (GPA) results show a significant relation between diabetic mellitus and GPA were P-value=0.026 and X2(11.008) increase in zero answer NO were (64.7%). Conclusion: The prevalence of of GDM among pregnant women's in obstetric clinics at MCH Makkah city 2019 was high. Previous history of GDM, antenatal family history of diabetes, low physical activity, overweight and/or obesity and inadequate dietary diversity were significantly associated with GDM. Routine screening of pregnant women and healthy lifestyle are strongly recommended.

Background Pancreatic neuroendocrine tumors (PNETs) are rare pancreas tumors, which represent less than 2% of all pancreatic tumors. The purpose of this study was to determine the incidence, clinicopathological characteristics, and prognostic factors for PNET survival predictions. Patients and methods This study included patients with PNETs treated at our center during the period from January 2007 until December 2017. For patients with PNETs, preoperative data, operative, postoperative data, and records of survival were analyzed. Results In our center, 720 patients underwent pancreatic surgery, including 71 patients (9.86%) with pathologically confirmed PNETs. There were 43 women (60.6%) and 28 men (39.4%), with a median age of 35 years, range 12–74 years. The PNETs were solitary in 65 (91.5%) patients, and the median diameter was 7 cm (range 1–18 cm). The tumors were located in the pancreatic head in 35 (49.3%) patients, body in six (8.5%) patients, and tail in 30 (42.2%) patients. Abdominal pain was the commonest presentation in 57 (80.3%) patients. Nonfunctioning PANETs presented in 65 (91.5%) patients. The overall recurrence rate was seven (9.9%) patients. The overall survival at 1, 3, and 5 years for all cases was 96, 85, and 72%, respectively, with a median survival of 85 months. Grade of tumor was the only independent factor for survival. Conclusion PNETs are rare pancreatic neoplasm more common in female sex. Nonfunctioning PNETS presented in most cases. Surgical resection was based on the site, size, and extension of the tumor. Grade of tumor was the only independent factor for survival.

Aim Pancreatic pseudocyst is the commonest cystic lesion of the pancreas. It usually develops on a background of pancreatitis. Cyst recurrence is the most feared complication following surgical management of pancreatic pseudocyst. Patients and methods The authors reviewed the data of 48 patients who were managed surgically during the period between 2010 and 2019. Results Biliary pancreatitis was the commonest cause (24 cases − 50%). The mean cyst size was 13.5±6.4 cm (6–42 cm). Most lesions were located in the body and tail of the pancreas (32 cases − 66.7%). Open approach was performed in 45 (93.8%) cases whereas the remaining cases were performed laparoscopically. Cases were managed by cystogastrostomy (39 cases − 81.3%), cyst-jejunostomy (seven cases − 14.6%), combined procedures (one case − 2.1%), or central pancreatectomy (one case − 2.1%). Cholecystectomy was performed in 17 (35.4%) cases. Early postoperative morbidity was encountered in nine (18.8%) cases. After a median follow-up of 68 months, no recurrence was detected. One (2.1%) case developed incisional hernia, and another one (2.1%) had adhesive intestinal obstruction. Conclusion Surgical intervention for pancreatic pseudocysts is a safe and feasible approach. It offers the ability to deal with the primary cause during operation and excellent long-term outcome regarding pseudocyst recurrence.