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Liver regeneration following resection is a complex process relying on coordinated pathways and cell types in the remnant organ. Myeloid-Derived Suppressor Cells (MDSCs) have a role in liver regeneration-related angiogenesis but other roles they may play in this process remain to be elucidated. In this study, we sought to examine the effect of G-MDSCs on hepatocytes proliferation and immune modulation during liver regeneration. Global gene expression profiling of regenerating hepatocytes in mice with CD11b + Ly6G + MDSCs (G-MDSCs) depletion revealed disrupted transcriptional progression from day one to day two after major liver resection. Key genes and pathways related to hepatocyte proliferation and immune response were differentially expressed upon MDSC depletion. Hepatocytes cellularity increased when co-cultured with G-MDSCs, or treated with amphiregulin, which G-MDSCs upregulate during regeneration. Cytometry by time-of-flight (CyTOF) analysis of the intra-liver immune milieu upon MDSC depletion during regeneration demonstrated increased natural killer cell proportions, alongside changes in other immune cell populations. Taken together, these results provide evidence that MDSCs contribute to early liver regeneration by promoting hepatocyte proliferation and modulating the intra-liver immune response, and illuminate the multifaceted role of MDSCs in liver regeneration., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Objective: Semaglutide, a glucagon-like peptide-1 receptor agonist is approved for weight loss and diabetes treatment, but limited literature exists regarding semaglutide use in patients with advanced chronic kidney disease (CKD). Therefore, this project assessed the safety and efficacy of semaglutide among patients with estimated glomerular filtration rate (eGFR) 15-29 mL/min/1.73 m 2 (CKD stage 4), eGFR<15 mL/min/1.73 m 2 (CKD stage 5) or on dialysis., Methods: This is a retrospective electronic medical record based analysis of consecutive patients with advanced CKD (defined as CKD 4 or greater) who were started on semaglutide (injectable or oral). Data was collected between January 2018 and January 2023. Investigators verified CKD diagnosis and manually extracted data. Data were analyzed using Fisher's exact test, paired t test, linear mixed effects models and Wilcoxon signed rank test., Results: Seventy-six patients with CKD 4 or greater who initiated semaglutide were included. Most patients had a history of type 2 diabetes mellitus (96.0%), and most were males (53.9%). The mean age was 66.8 y (SD 11.5) with the mean body mass index was 36.2 (SD 7.5). The initial doses were 3 mg orally and 0.25 mg by injection. Maximum prescribed dose was 1 mg (injectable) in 28 (45.2%) patients and 14 mg (orally) in 2 (14.2%) patients. Patients received semaglutide for a median duration of 17.4 (IQR 0.43, 48.8) months. Forty-eight (63.1%) patients reported no adverse effects associated with the therapy. Mean weight decreased from 106.2 (SD 24.2) to 101.3 (SD 27.3) kg (P < .001). Eight patients (16%) with type 2 diabetes mellitus T2DM discontinued insulin after starting semaglutide. Mean hemoglobin A1c (HbA1c) decreased from 8.0% (SD 1.7) to 7.1% (SD 1.3) (P < .001). Adverse effects were the primary reason for semaglutide discontinuation (37.0%), with nausea, vomiting, and abdominal pain being the most common complaints., Conclusions: Based on this retrospective study semaglutide appears to be tolerated by most individuals with CKD 4 or greater despite associated gastrointestinal side effects similar to those observed in patients with better kidney function and leads to an improvement of glycemic control and insulin discontinuation in patients with T2DM. Modest weight loss (approximately 4.6% of the total body weight) was observed on the prescribed doses. Larger prospective randomized studies are needed to comprehensively assess the risks and benefits of semaglutide in patients with CKD 4 or greater and obesity., Competing Interests: Disclosure Dr Aleksandra Kukla participated in NovoNordisk Advisory Board in 2020 but recieved no personal compensation. Dr Matthew M. Clark, Associate Editor, Obesity. Intellectual Property, Phenomix Science, Inc, Pheno-Diet: Individualized Lifestyle Intervention for Obesity Management Based on Obesity Phenotypes., (Copyright © 2024 AACE. Published by Elsevier Inc. All rights reserved.)

Background: Individualizing induction therapy based on immunological risk is crucial for optimizing outcomes in kidney transplantation., Methods: A retrospective analysis included 157 first live-donor non-sensitized kidney transplant recipients (KTRs). Within this cohort, 96 individuals exhibited low human leukocyte antigen (HLA) matching (5-6 HLA mismatches). The low HLA match subgroup was categorized into 52 KTRs receiving basiliximab alone and 44 recipients treated with a combined single ATG dose of 1.5 mg/kg and basiliximab. The primary endpoint was early acute cellular rejection (ACR) within 6 months post-transplant while secondary outcomes encompassed infection rates, renal allograft function, length of stay (LOS) and readmissions post-transplant., Results: The incidence of early ACR was decreased for low HLA match KTRs, who received ATG-basiliximab, when compared with low HLA-matched KTRs who received basiliximab alone (9.1% vs 23.9%, P  = .067). Age was a predictor for rejection, and subgroup analysis showed consistent rejection reduction across age groups. No significant differences were observed in admission for transplant LOS or in peri-operative complications, nor in infections rate including BK and cytomegalovirus viremia, allograft function and number of readmissions post-transplant up to 6 months post-transplant., Conclusion: In non-sensitized first live-donor KTRs with low HLA matching, a dual ATG-basiliximab induction approach significantly reduced early ACR without compromising safety., Competing Interests: The authors declare no conflicts of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of the ERA.)

Background: Predicting long-term mortality postkidney transplantation (KT) using baseline clinical data presents significant challenges. This study aims to evaluate the predictive power of artificial intelligence (AI)-enabled analysis of preoperative electrocardiograms (ECGs) in forecasting long-term mortality following KT., Methods: We analyzed preoperative ECGs from KT recipients at three Mayo Clinic sites (Minnesota, Florida, and Arizona) between January 1, 2006, and July 30, 2021. The study involved 6 validated AI algorithms, each trained to predict future development of atrial fibrillation, aortic stenosis, low ejection fraction, hypertrophic cardiomyopathy, amyloid heart disease, and biological age. These algorithms' outputs based on a single preoperative ECG were correlated with patient mortality data., Results: Among 6504 KT recipients included in the study, 1764 (27.1%) died within a median follow-up of 5.7 y (interquartile range: 3.00-9.29 y). All AI-ECG algorithms were independently associated with long-term all-cause mortality ( P < 0.001). Notably, few patients had a clinical cardiac diagnosis at the time of transplant, indicating that AI-ECG scores were predictive even in asymptomatic patients. When adjusted for multiple clinical factors such as recipient age, diabetes, and pretransplant dialysis, AI algorithms for atrial fibrillation and aortic stenosis remained independently associated with long-term mortality. These algorithms also improved the C-statistic for predicting overall (C = 0.74) and cardiac-related deaths (C = 0.751)., Conclusions: The findings suggest that AI-enabled preoperative ECG analysis can be a valuable tool in predicting long-term mortality following KT and could aid in identifying patients who may benefit from enhanced cardiac monitoring because of increased risk., Competing Interests: The authors declare no funding or conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

The mouse small intestine shows profound variability in gene expression along the crypt-villus axis 1,2 . Whether similar spatial heterogeneity exists in the adult human gut remains unclear. Here we use spatial transcriptomics, spatial proteomics and single-molecule fluorescence in situ hybridization to reconstruct a comprehensive spatial expression atlas of the adult human proximal small intestine. We describe zonated expression and cell type representation for epithelial, mesenchymal and immune cell types. We find that migrating enterocytes switch from lipid droplet assembly and iron uptake at the villus bottom to chylomicron biosynthesis and iron release at the tip. Villus tip cells are pro-immunogenic, recruiting γδ T cells and macrophages to the tip, in contrast to their immunosuppressive roles in mouse. We also show that the human small intestine contains abundant serrated and branched villi that are enriched at the tops of circular folds. Our study presents a detailed resource for understanding the biology of the adult human small intestine., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Incisional hernias (IH) are a significant postoperative complication with profound implications for patient morbidity and healthcare costs. The relationship between IH and perioperative factors in pancreatic surgery, with particular attention to preoperative biliary stents and pancreatic fistulas requires further exploration., Methods: This retrospective observational study examined adult patients who underwent open pancreatic surgeries via midline incision at a high-volume tertiary hepatopancreatobiliary center from January 2008 to December 2021. The study focused on IH incidence and associated risk factors, with particular attention to preoperative biliary stents and pancreatic fistulas., Results: In a cohort of 620 individuals undergoing pancreatic surgery, 351 had open surgery with at least one-year follow-up. Within a median follow-up of 794 days (IQR 1694-537), the overall incidence of IH was 17.38%. The highest frequency of IH was observed among patients who had a Pancreaticoduodenectomy (PD). Significant predictors for the development of IH within the entire study population in a multivariable analysis included perioperative biliary stenting (OR 2.05; 95% CI 1.06-3.96; p = 0.03), increased age at diagnosis (OR 2.05; 95% CI 1.06-3.96; p = 0.01), and BMI (OR 1.08; 95% CI 1.01-1.15; p = 0.01). In the subset of patients who underwent Pancreaticoduodenectomy (PD), although the presence of biliary stents was associated with a heightened occurrence of SSIs, it did not demonstrate a direct correlation with an increased incidence of incisional hernias (IH). The development of pancreatic fistulas did not show a significant correlation with IH in either the Distal Pancreatectomy with Splenectomy (DPS) or the PD patient groups., Conclusions: The study underscores a notable association between biliary stent placement and increased IH risk after PD, mediated by elevated SSI incidence. Pancreatic fistulas were not directly correlated with IH in the studied cohorts. Further research is necessary to validate these findings and guide clinical practice., (© 2024. The Author(s).)

Introduction: In select clinical scenarios, advanced techniques for volume manipulation and vascular reconstruction are needed for complete hepatic tumor removal. These highly complex liver resections (HCLRs) entail a heightened risk of severe complications. Here, we describe the results of HCLR performed in a 3-year time period., Materials and Methods: We conducted a retrospective analysis encompassing patients who underwent hepatic resections between June 15, 2020, and June 15, 2023. HCLR was defined according to previously established criteria, and included associating liver partition and portal vein ligation for staged hepatectomy. The outcomes of HCLR were compared to all non-HCLR performed within the same time frame., Results: Among 167 hepatic resections, 26 were considered HCLR, and all were major resections. Five utilized total vascular exclusion, with venovenous bypass in three, and hypothermic liver perfusion in three. Five resections included vascular reconstructions, and one included hypothermic circulatory arrest for extraction of a tumor extending to the right atrium. Of the non-HCLR, 38 (26.9%) were major, and 49 (34.7%) were performed laparoscopically. The rates of overall major postoperative complications were comparable between those who underwent HCLR versus non-HCLR. HCLR was associated with increased rates of biliary complications, readmissions, and reoperation. However, no postoperative 90-day mortality was documented within patients that underwent HCLR compared to two in the non-HCLR group., Conclusions: In expert hands, HCLR can be performed with acceptable complication profile, akin to that of major non-HCLR. Those with questionable resectability should be referred to tertiary hepato-pancreato-biliary centers., (© 2024 Wiley Periodicals LLC.)

Background: The value of platelet characteristics as a prognostic factor in patients with pancreatic adenocarcinoma (PDAC) remains unclear., Methods: We assessed the prognostic ability of post-splenectomy thrombocytosis in patients who underwent left pancreatectomy for PDAC. Perioperative platelet count ratio (PPR), defined as the ratio between the maximum platelet count during the first five days following surgery and the preoperative level, was assessed in relation to long-term outcomes in patients who underwent left pancreatectomy for PDAC between November 2008 and October 2022., Results: A comparative cohort of 245 patients who underwent pancreaticoduodenectomy for PDAC was also evaluated. The median PPR among 106 patients who underwent left pancreatectomy was 1.4 (IQR1.1, 1.8). Forty-six had a PPR ≥ 1.5 (median 1.9, IQR1.7, 2.4) and 60 had a PPR < 1.5 (median 1.2, IQR1.0, 1.3). Patients with a PPR ≥ 1.5 had increased median overall survival (OS) compared to patients with a PPR < 1.5 (40 months vs. 20 months, p < 0.001). In multivariate analysis, PPR < 1.5 remained a strong predictor of worse OS (HR 2.24, p = 0.008). Among patients who underwent pancreaticoduodenectomy, the median PPR was 1.1 (IQR1.0, 1.3), which was significantly lower compared to patients who underwent left pancreatectomy ( p > 0.001) and did not predict OS., Conclusion: PPR is a biomarker for OS after left pancreatectomy for PDAC. Further studies are warranted to consolidate these findings.

The impact of bariatric surgery (BS) on kidney transplantation (KT) outcomes in patients with obesity remains controversial. We systematically searched MEDLINE, EMBASE, Scopus, Web of Science, and Cochrane Central Register of Controlled Trials for studies reporting outcomes of KT recipients that underwent prior BS. Common/random effects meta-analyses were performed to obtain summary ratios of the postoperative outcomes. Eighteen eligible studies involving 315 patients were identified. Sleeve gastrectomy was the most common BS type (65.7%) followed by Roux-en-Y gastric bypass (27.6%) and gastric banding (4.4%). Across studies that provided the data, the %excess weight loss from BS to KT was 62.79% (95% confidence interval [CI], 52.01-73.56; range, 46.2%-80.3%). The rates of delayed graft function and acute rejection were 16% (95% CI, 7%-28%) and 16% (95% CI, 11%-23%) in 14 and 11 studies that provided this data, respectively. The rates of wound, urinary, and vascular complications following KT were 5% (95% CI, 0%-13%),19% (95% CI, 2%-42%), and 2% (95% CI, 0%-5%), in 12, 9, and 11 studies that provided this data, respectively. Follow-up time after KT was reported in 11 studies (61.1%) and ranged from 16 mo to >5 y. Graft loss was reported in 14 studies with an average of 3% (95% CI, 1%-6%). Four studies that included a comparator group of patients with obesity who did not undergo BS before KT showed comparable outcomes between the groups. We conclude that currently there is a paucity of robust evidence to suggest that pretransplant BS has a major effect on post-KT outcomes. High-quality studies are needed to fully evaluate the impact of BS on KT outcomes., Competing Interests: The authors declare no funding or conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Major abdominal wall defects remain a highly morbid complication. Occasionally a fascial defect is encountered, that despite all surgical efforts, is unable to completely approximate at the midline. Here we describe our method and outcomes of using a bridging mesh when the posterior fascia was unable to be approximated during the repair of large postoperative ventral hernias using the modified Rives-Stoppa technique., Methods: A retrospective review was conducted looking at all the open abdominal wall hernia repairs between 2014 and 2020. The cohort of patients who had a bridge placed in addition to the traditional open modified Rives-Stoppa repair were used for this study., Results: Nineteen patients had a mesh inlay bridge placed in addition to a modified Rives-Stoppa repair with a sublay (retrorectus) Ultrapro mesh. For the inlay mesh 13 Symbotex composite meshes were placed and 6 Vicryl meshes used. The average surface area of the defect was 358.1 cm^2. The average length of hospitalization was 8.8 days with a range of 3-24 days. During the immediate postoperative course there were 6 minor complications. During the follow-up period there were 2 recurrences., Discussion: The use of inlay mesh bridge as an adjuvant to a modified Rives-Stoppa repair with a sublay ultrapro mesh is an effective technique for difficult abdominal wall repairs where the posterior fascia is unable to be approximated without tension., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

BACKGROUND Bariatric surgeries, such as one anastomosis gastric bypass (OAGB), has become a popular treatment option for managing obesity and associated comorbidities, including type-2 diabetes mellitus (T2DM). However, severe starvation ketoacidosis is a rare but potentially life-threatening complication that can occur postoperatively in patients with T2DM. Despite the increasing prevalence of these surgeries, the existing literature has limited information on severe starvation ketoacidosis as a postoperative complication. It is essential for healthcare professionals to be aware of this complication, its manifestations, and risk factors to ensure patient safety and improve outcomes. Therefore, this article aims to address the current gap in the literature and provide a comprehensive review of severe starvation ketoacidosis as a postoperative complication of bariatric surgeries, specifically OAGB, and its associated risk factors and manifestations. CASE REPORT A 38-year-old man with severe obesity and inadequately managed T2DM underwent OAGB surgery. On the second postoperative day, the patient experienced severe starvation ketoacidosis, exhibiting symptoms such as drowsiness, fatigue, weakness, and Kussmaul breathing. Blood gas analysis indicated significant metabolic acidosis. He was quickly transferred to the Intensive Care Unit (ICU) and given intravenous glucose and insulin therapy. Following this intervention, he showed rapid recovery and normalization of blood gases. He was discharged 6 days after surgery with normal clinical examination results and laboratory indices. CONCLUSIONS This case study emphasizes the significance of thorough preoperative glycemic control, comprehensive perioperative multidisciplinary management, and close postoperative monitoring for diabetic patients undergoing metabolic and bariatric surgeries. By implementing these strategies, healthcare professionals can reduce the risk of complications such as hypoglycemia or hyperglycemia/diabetic ketoacidosis (DKA) and enhance patient outcomes. The case also highlights the need for continuous education and training for healthcare providers to identify and manage such rare complications effectively.

Background: Data regarding laparoscopic liver resections(LLRs) for Gallbladder cancer(GBC) and Intrahepatic Cholangiocarcinoma(iCCA) are sparse. This study compared LLRs with open liver resections(OLRs) in a high-volume center., Methods: Data of patients who underwent LLR or OLR for GBC or iCCA at Mayo-Clinic between 01/2016 and 04/2021 were retrospectively compared. Proportional hazards models were used to compare the approach on survival., Results: 32 and 52 patients underwent LLR and OLR during the study period, respectively. 64 and 20 patients had iCCA and GBC, respectively. LLR had lower median blood loss (250 mL vs. 475 mL, p = 0.001) and shorter median length of stay compared to OLR (3.0 days vs. 6.0 days, p = 0.001). LLR and OLR did not differ in post-operative major complication (25% vs. 32.7%, p = 0.62), negative margin (100% vs. 90.4%, p = 0.15) and completeness of lymphadenectomy rates (36.8% vs. 45.5%, p = 0.59). The median number of harvested lymph node was 4.0 and 5.0 for LLR and OLR, respectively (p = 0.347). There were no associations between approach and 3-year overall and disease-free survival between LLR and OLR (49.8% vs. 63.2% and 39.6% vs. 21.5%, p = 0.66 and p = 0.69)., Discussion: With appropriate patient selection and when compared to OLRs, LLRs for GBC and iCCA are feasible, safe and offer potential short-term benefits without compromising on oncological resection principals and long-term outcomes., (Copyright © 2023 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Purpose: Ileostomy is associated with various complications, often necessitating rehospitalization. High-output ileostomy is common and may lead to acute kidney injury (AKI). Here we describe the temporal pattern of readmission with AKI following ileostomy formation and identify risk factors., Methods: Patients that underwent formation of ileostomy between 2008 and 2021 were included in this study. Readmission with AKI with high output ileostomy was defined as readmission with serum creatinine > 1.5-fold compared to the level at discharge or latest baseline (at least stage-1 AKI according to Kidney Disease: Improving Global Outcome (KDIGO) criteria), accompanied by ileostomy output > 1000 ml in 24 h. Patient characteristics and perioperative course were assessed to identify predictors for readmission with AKI., Results: Of 1191 patients who underwent ileostomy, 198 (16.6%) were readmitted with a high output stoma and AKI. The mean time to readmission with AKI was 98.97 ± 156.36 days. Eighty-six patients (43.4%) had early readmission (within 30 days), and 66 (33%) were readmitted after more than 90 days. Over 90% of patients had more than one readmission, and 110 patients (55%) had 5 or more. Patient-related predictors for readmission with AKI were age > 65, body mass index > 30 kg/m 2 , and hypertension. Factors related to the postoperative course were AKI with creatinine > 2 mg/dl, postoperative hemoglobin < 8 g/dl or blood transfusion, albumin < 20 g/dl, high output stoma and need for loperamide, and length of hospital stay > 20 days. Factors related to early versus late readmissions and multiple readmissions were also analyzed., Conclusions: Readmission with AKI following ileostomy formation is a consequential event with distinct risk factors. Acknowledging these risk factors is the foundation for designing interventions aiming to reduce frequency of AKI readmissions in predisposed patient populations., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: Intraoperative ultrasonography (IOUS) of the liver is a crucial adjunct in every liver resection and may significantly impact intraoperative surgical decisions. However, IOUS is highly operator dependent and has a steep learning curve. We describe the design and assessment of an artificial intelligence (AI) system to identify focal liver lesions in IOUS., Methods: IOUS images were collected during liver resections performed between November 2020 and November 2021. The images were labeled by radiologists and surgeons as normal liver tissue versus images that contain liver lesions. A convolutional neural network (CNN) was trained and tested to classify images based on the labeling. Algorithm performance was tested in terms of area under the curves (AUCs), accuracy, sensitivity, specificity, F1 score, positive predictive value, and negative predictive value., Results: Overall, the dataset included 5043 IOUS images from 16 patients. Of these, 2576 were labeled as normal liver tissue and 2467 as containing focal liver lesions. Training and testing image sets were taken from different patients. Network performance area under the curve (AUC) was 80.2 ± 2.9%, and the overall classification accuracy was 74.6% ± 3.1%. For maximal sensitivity of 99%, the classification specificity is 36.4 ± 9.4%., Conclusions: This study provides for the first time a proof of concept for the use of AI in IOUS and show that high accuracy can be achieved. Further studies using high volume data are warranted to increase accuracy and differentiate between lesion types., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Endoscopic retrograde cholangiopancreatography (ERCP) is the first line treatment for choledocholithiasis. In many occasions, several attempts of ERCP are performed until failure is declared and surgical treatment is applied, in many times following procedure-related complications. We present the results of surgical management of patients with choledocholithiasis following repeated failures of ERCP due to impaction of multiple large stones., Methods: Patients that underwent surgical treatment for choledocholithiasis following repeated ERCP attempts between January 2006 and December 2018 were retrospectively assessed. Post-ERCP complications were evaluated and the surgical approach, technique, and outcomes were assessed., Results: One hundred and two patients were operated on for choledocholithiasis following repeated failed ERCP. All the patients had at least 2 failed attempts (mean = 3.2 ± 1.7), and 25 (23.5%) suffered major ERCP-related complications. Following choledochotomy and stone extraction, bilioenteric anastomosis was done in the vast majority of patients (90.2%), most commonly choledochoduodenostomy (62%). Thirty-eight (37%) patients had minimally invasive procedure (laparoscopic n = 26, robotic assisted n = 12). Major post-operative complications (Clavien-Dindo ≥ 3) occurred in 24 patients (23.5%). Nine patients (8.8%) were re-operated and 10 (9.8%) were readmitted within 30 days from surgery. Three patients died within 30 days from surgery. Older patients had significantly more ERCP attempts and suffered higher post-operative mortality. During a median follow-up of 70 months, the only biliary complication was an anastomotic stricture in one patient., Conclusion: Surgery for CBDS after failure of ERCP is safe and provides a highly effective long-term solution., (© 2022. The Society for Surgery of the Alimentary Tract.)

Background: Histologic confirmation before pancreaticoduodenectomy (PD) for suspected pancreatic cancer is often performed. We assessed the yield of preoperative biopsy in these patients considering the associated complications., Methods: We retrospectively evaluated 216 patients that underwent PD for suspected carcinoma (CA) between 2012 and 2018. Post procedure complications and delay in surgery were assessed, as well as the postoperative diagnosis in relation to preoperative parameters., Results: Preoperative biopsy was performed in 142 patients (65.7%). Pathologic findings suggestive of CA were found in 106 (74.6%), while benign histology was found in 23 (16.1%), and non-diagnostic findings in 12 (8.4%). Seventy-four patients (34.3%) were operated without a preoperative biopsy. The time from diagnosis to surgery was significantly prolonged in those that underwent biopsy compared to patients that were taken straight to surgery (40±14 versus 18±15 days, P<0.001), and 18 patients (12.6%) suffered from clinically significant post procedure complications. Patients with a preoperative biopsy suggestive of CA, and those that were operated without a preoperative histologic confirmation had comparable rates of CA as a final pathological diagnosis (95.2% and 94.5%, respectively). Nevertheless, in patients with a benign or a non-diagnostic biopsy, the rates of pathologic diagnosis of CA were 69.6% and 73.6% respectively. Elevated levels of CA19-9 and a positive preoperative biopsy were associated with a final pathology of CA., Conclusions: Preoperative histology is not uniformly required in patients with suspected pancreatic cancer. If preoperative biopsy is performed, benign histology does not rule out cancer but warrants additional evaluation prior to surgery.

Tumor-treating fields (TTFields) are a localized, antitumoral therapy using alternating electric fields, which impair cell proliferation. Combining TTFields with tumor immunotherapy constitutes a rational approach; however, it is currently unknown whether TTFields' locoregional effects are compatible with T cell functionality. Healthy donor PBMCs and viably dissociated human glioblastoma samples were cultured under either standard or TTFields conditions. Select pivotal T cell functions were measured by multiparametric flow cytometry. Cytotoxicity was evaluated using a chimeric Ag receptor (CAR)-T-based assay. Glioblastoma patient samples were acquired before and after standard chemoradiation or standard chemoradiation + TTFields treatment and examined by immunohistochemistry and by RNA sequencing. TTFields reduced the viability of proliferating T cells, but had little or no effect on the viability of nonproliferating T cells. The functionality of T cells cultured under TTFields was retained: they exhibited similar IFN-γ secretion, cytotoxic degranulation, and PD1 upregulation as controls with similar polyfunctional patterns. Glioblastoma Ag-specific T cells exhibited unaltered viability and functionality under TTFields. CAR-T cells cultured under TTFields exhibited similar cytotoxicity as controls toward their CAR target. Transcriptomic analysis of patients' glioblastoma samples revealed a significant shift in the TTFields-treated versus the standard-treated samples, from a protumoral to an antitumoral immune signature. Immunohistochemistry of samples before and after TTFields treatment showed no reduction in T cell infiltration. T cells were found to retain key antitumoral functions under TTFields settings. Our data provide a mechanistic insight and a rationale for ongoing and future clinical trials that combine TTFields with immunotherapy., (Copyright © 2021 by The American Association of Immunologists, Inc.)

Negative endoscopic retrograde cholangiopancreatography (ERCP) for suspected common bile duct stones (CBDS) may be associated with significant morbidity and should be avoided. Between 2010 and 2018, 85 patients who have undergone negative ERCP for suspected CBDS were retrospectively evaluated and compared with 318 patients with positive findings. Predictors for negative ERCP were assessed. Patients with negative ERCP were younger; had increased levels of serum amylase, alanine transaminase, and lactate dehydrogenase; and increased hemoglobin. Even though preprocedure computed tomography (CT) or ultrasonography demonstrating CBDS were highly predictive of positive findings on ERCP, of the 212 patients with CBDS on computed tomography or ultrasonography, 17 (8%) eventually had a negative ERCP, suggesting spontaneous stone passage. An increased serum amylase level was the only predictor for negative ERCP in multivariate analysis, including in patients with preprocedure CBDS on imaging. The data suggest that assessing serum amylase may assist in avoiding unnecessary examinations., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Accumulation of plasma mitochondrial DNA (mtDNA) following severe trauma has been shown to correlate with the development of systemic inflammatory response syndrome (SIRS) and may predict mortality. Our objective was to investigate the relationship between levels of circulatory mtDNA following pancreaticoduodenectomy (PD) and the postoperative course., Methods: Levels of plasma mtDNA were assessed by real-time PCR of the mitochondrial genes ND1 and COX3 in 23 consecutive patients who underwent PD 1 day prior to surgery, within 8 h after surgery, and on postoperative day (POD)1 and POD5. The abundance of mtDNA was assessed relative to preoperative levels and in relation to parameters reflecting the postoperative clinical course., Results: When pooled for all patients, the circulating mtDNA levels were significantly increased after surgery. However, while a significant (at least >2-fold and up to >20-fold) rise was noted in 11 patients, no change in mtDNA levels was noted in the other 12 following surgery. Postoperative rise in circulating mtDNA was associated with an increased rate of postoperative fever until day 5, decreased hemoglobin and albumin levels, and increased white blood cell counts. These patients also suffered from increased rates of delayed gastric emptying. No significant differences were demonstrated in other postoperative parameters., Conclusion: Circulating mtDNA surge is associated with an inflammatory response following PD and may potentially be used as an early marker for postoperative course. Studies of larger patient cohorts are warranted., (© 2021 The Author(s) Published by S. Karger AG, Basel.)

Background: Recent data demonstrates that laparoscopic adjustable gastric banding (LAGB) is found to be associated with high rates of weight loss failure and long-term complications. Therefore, the search for the optimal revisional bariatric procedure is ongoing., Objective: We aim to assess the safety and efficacy of converting a failed LAGB to laparoscopic one anastomosis gastric bypass (OAGB) as a revisional procedure., Setting: Large, metropolitan, tertiary, university hospital., Methods: Retrospective review of patients who underwent OAGB after LAGB.Demographics, comorbidities, BMI before and after the procedure, complications, and length of stay were documented., Results: Fifty-seven patients underwent OAGB after LAGB. For 41 patients, the band was removed, and an OAGB was performed in a single procedure (71.9%), and 96.5% of the cases were completed laparoscopically. Postoperative complications occurred in 9 patients (15.7%), including one mortality. Average BMI decreased from 42.8 ± 7.0 to 31.3 ± 5.2 kg/m 2 at least 1 year after surgery, representing a mean %EWL of 64.5%. There was no statistical difference in complication rates between the 1-stage and 2-stage approach., Conclusions: Conversion of a failed LAGB to OAGB is effective but carries higher complication rates. Randomized controlled studies comparing different procedures are necessary to further clarify the optimal revisional bariatric operation.

Background: As advances in oncological treatment continue to prolong the survival of patients with non-resectable pancreatic ductal adenocarcinoma (PDAC), decision-making regarding palliative surgical bypass in patients with a heavy disease burden turns challenging. Here we present the results of a pancreatic surgery referral center., Methods: Patients that underwent palliative gastrojejunostomy and/or hepaticojejunostomy for advanced, non-resectable PDAC between January 2010 and November 2018 were retrospectively assessed. All patients were taken to a purely palliative surgery with no curative intent. The postoperative course as well as short and long-term outcomes was evaluated in relation to preoperative parameters., Results: Forty-two patients (19 females) underwent palliative bypass. Thirty-one underwent only gastrojejunostomy (22 laparoscopic) and 11 underwent both gastrojejunostomy and hepaticojejunostomy (all by an open approach). Although 34 patients (80.9%) were able to return temporarily to oral intake during the index admission, 15 (35.7%) suffered from a major postoperative complication. Seven patients (16.6%) died from surgery and another seven within the following month. Nine patients (21.4%) never left the hospital following the surgery. Mean length of hospital stay was 18 ± 17 days (range 3-88 days). Mean overall survival was 172.8 ± 179.2 and median survival was 94.5 days. Age, preoperative hypoalbuminemia, sarcopenia, and disseminated disease were associated with palliation failure, defined as inability to regain oral intake, leave the hospital, or early mortality., Conclusions: Although palliative gastrojejunostomy and hepaticojejunostomy may be beneficial for specific patients, severe postoperative morbidity and high mortality rates are still common. Patient selection remains crucial for achieving acceptable outcomes.

Myeloid derived suppressor cells (MDSCs) play key roles in cancer development. Accumulation of peripheral-blood MDSCs (PB-MDSCs) corresponds to the progression of various cancers, but provides only a crude indicator. We aimed toward identifying changes in the transcriptional profile of PB-MDSCs in response to tumor growth. CT26 colon cancer cells and B16 melanoma cells (10 6 ) were inoculated into peritoneal cavities of BALB/c mice and subcutaneously to C57-black mice, respectively. The circulating levels and global transcriptional patterns of PB CD11b + Ly6g + MDSCs were assessed in control mice, and 4, 8, and 11 days following tumor cell inoculation. Although a significant accumulation of PB-MDSCs was demonstrated only 11 days following tumor induction, a pronounced transcriptional response was identified already on day 4 while the tumor was ~1 mm in size. Further transcriptional changes correlated with different stages of tumor growth. Key MDSC genes and canonical signaling pathways were activated along tumor progression. This phenomenon was demonstrated in both cancer models, and a consensus set of 817 genes, involved in myeloid cell recruitment and angiogenesis, was identified. The data suggest that the transcriptional signatures of PB-MDSC may serve as markers for tumor progression, as well as providing potential targets for future therapies.

Liver regeneration depends on sequential activation of pathways and cells involving the remaining organ in recovery of mass. Proliferation of parenchyma is dependent on angiogenesis. Understanding liver regeneration-associated neovascularization may be useful for development of clinical interventions. Myeloid-derived suppressor cells (MDSCs) promote tumor angiogenesis and play a role in developmental processes that necessitate rapid vascularization. We therefore hypothesized that the MDSCs could play a role in liver regeneration. Following partial hepatectomy, MDSCs were enriched within regenerating livers, and their depletion led to increased liver injury and postoperative mortality, reduced liver weights, decreased hepatic vascularization, reduced hepatocyte hypertrophy and proliferation, and aberrant liver function. Gene expression profiling of regenerating liver-derived MDSCs demonstrated a large-scale transcriptional response involving key pathways related to angiogenesis. Functionally, enhanced reactive oxygen species production and angiogenic capacities of regenerating liver-derived MDSCs were confirmed. A comparative analysis revealed that the transcriptional response of MDSCs during liver regeneration resembled that of peripheral blood MDSCs during progression of abdominal tumors, suggesting a common MDSC gene expression profile promoting angiogenesis. In summary, our study shows that MDSCs contribute to early stages of liver regeneration possibly by exerting proangiogenic functions using a unique transcriptional program.-Nachmany, I., Bogoch, Y., Sivan, A., Amar, O., Bondar, E., Zohar, N., Yakubovsky, O., Fainaru, O., Klausner, J. M., Pencovich, N. CD11b + Ly6G + myeloid-derived suppressor cells promote liver regeneration in a murine model of major hepatectomy.

Background and Objectives: The impact of resection margins on the outcome of patients with colorectal liver metastasis (CRLM) remains controversial. We evaluated the short and long-term results of R1 resection., Methods: Between 2006 and 2016, 202 patients underwent liver resection for CRLM. R1 resection was defined as a distance of less than 1 mm between tumor cells and the transection plain. Patient and tumor characteristics, perioperative, and long-term outcomes were assessed., Results: In 161 (79.7%) and 41 (20.3%) patients, an R0 and R1 resections were achieved, respectively. Patients that underwent an R1 resection had higher rates of disease progression while on chemotherapy (12.1% vs 5.5%, P = 0.001), need for second-line chemotherapy (17% vs 6.2%, P < 0.001), increased use of preoperative volume manipulation (14.6% vs 5.5%, P = 0.001), and inferior vena-cava involvement (21.9% vs 8.7%, P < 0.001). These patients had higher rates of major postoperative complications (19.5% vs 6.8%, P < 0.001) and reoperations (7.3% vs 2.4%, P < 0.001). Multivariate analysis demonstrated that R1 resections were not associated with decreased recurrence-free survival or overall survival., Conclusions: Although R1 resection is associated with worse disease behavior and postoperative complications, the long-term outcome of patients following an R1 resection is non-inferior to those who underwent an R0 resection., (© 2018 Wiley Periodicals, Inc.)

Introduction: immature-myeloid cells (IMCs) are proangiogenic bone marrow (BM)-derived cells that normally differentiate into inflammatory cells such as neutrophils, monocytes and dendritic cells (DCs). We characterized placental IMCs comparing their gene expression and subpopulations to tumor IMCs, and tested our hypothesis that progesterone that inhibits preterm labor, may affect their abundance and differentiation., Methods: differences between IMC-subpopulations in subcutaneous tumors versus placentas in C57BL/6 or ICR (CD-1) mice were analyzed by flow cytometry and gene expression was detected by microarrays. BM- and placental cells were incubated with or without progesterone and IMC subpopulations were analyzed. For preterm labor induction pregnant mice pretreated or not with progesterone were or were not treated with Lipopolysaccharide (LPS)., Results: we detected enrichment of granulocytic-IMCs in placentas compared to tumors, paralleled by a decrease in monocytic-IMCs. mRNA expression of placenta- versus tumor IMCs revealed profound transcriptional alterations. Progesterone treated BM-CD11b + cells ex-vivo induced enrichment of granulocytic-IMCs and a decrease in monocytic-IMCs and DCs. LPS treatment in-vivo led to an increase in BM-IMCs in both progesterone pretreated or non-pretreated mice. In the placenta LPS decreased the IMC population while progesterone led to complete abrogation of this effect., Discussion: placental IMCs differ from tumor-IMCs in both subpopulations and gene expression. Progesterone enhances the proliferation of placenta-specific granulocytic IMCs ex-vivo and LPS induced labor is accompanied by a decrease in placental IMCs only in progesterone non-pretreated mice. We thus speculate that the protective effect of progesterone in preventing preterm labor may be explained at least in part by this specific anti-inflammatory effect., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Reoperation following PD is a surrogate marker for a complex post-operative course and may lead to devastating consequences. We evaluate the indications for early reoperation following PD and analyze its effect on short- and long-term outcome., Methods: Four hundred and thirty-three patients that underwent PD between August 2006 and June 2016 were retrospectively analyzed., Results: Forty-eight patients (11%; ROp group) underwent 60 reoperations within 60 days from PD. Forty-two patients underwent 1 reoperation, and 6 had up to 6 reoperations. The average time to first reoperation was 10.1 ± 13.4 days. The most common indications were anastomotic leaks (22 operations in 18 patients; 37.5% of ROp), followed by post-pancreatectomy hemorrhage (PPH) (14 reoperations in 12 patients; 25%), and wound complications in 10 (20.8%). Patients with cholangiocarcinoma had the highest reoperation rate (25%) followed by ductal adenocarcinoma (12.3%). Reoperation was associated with increased length of hospital stay and a high post-operative mortality of 18.7%, compared to 2.6% for the non-reoperated group. For those who survived the post-operative period, the overall and disease-free survival were not affected by reoperation., Conclusions: Early reoperations following PD carries a dramatically increased mortality rate, but has no impact on long-term survival.

Background: Major liver resection during pregnancy is extremely rare. When required, the associated physiologic and anatomic changes pose specific challenges and greater risk for both mother and fetus Materials and methods: Three cases of major liver resection during pregnancy due to different etiologies are presented. The relevant literature is reviewed and discussed., Results: We present three cases of major liver resection due to giant liver hemangioma with Kasabach-Merrit syndrome, giant hydatid cyst, and intrahepatic cholangiocarcinoma, at gestational week (GW) 17, 19, and 30, respectively. All patients had an uneventful postoperative course, continued the pregnancy and gave birth at GW 38., Conclusion: Major liver resection can be performed safely during pregnancy. A multidisciplinary team of surgeons, anesthesiologists and gynecologists, in a highly experienced tertiary hepatobiliary center, should be involved.

Background: Diabetes and other obesity-related diseases are a worldwide pandemic that transcends geographic borders as well as socioeconomic levels. Currently, it is well known that medical treatment alone is insufficient to ensure adequate and sustainable weight loss and co-morbidity resolution. It has been well proven that bariatric surgery can produce almost immediate resolution of diabetes and other co-morbidities as well as long-term weight loss., Objectives: Here, we present our experience with the one anastomosis gastric bypass (OAGB) in terms of weight loss and diabetes resolution with 1 year of follow-up., Setting: Large, metropolitan, tertiary, university hospital., Methods: A retrospective analysis of all patients who underwent OAGB between March 2015 and March 2016 was performed. Patient demographic characteristics, co-morbidities, operative and postoperative data, as well as first year outcomes were collected and analyzed., Results: There were 407 patients who underwent OAGB (254 females, average age 41.8 ± 12.05 yr, body mass index = 41.7 ± 5.77 kg/m 2 ). Of patients, 102 (25.1%) had diabetes with average glycosylated hemoglobin of 8.64 ± 1.94 g%, 93 (22.8%) had hypertension, 123 (28.8%) had hyperlipidemia, and 35 patients (8.6%) had obstructive sleep apnea. The average length of hospital stay was 2.2 ± .84 days (range, 2-10 d). The average excess weight loss 1 year after surgery was 88.9 ± 27.3. After 1 year, follow-up data were available for more than 85% of the study's general population. Of 102 diabetic patients, only 8 (7.8%) were still considered diabetic and taking antidiabetic medication, with an average glycosylated hemoglobin of 5.4 ± 0.6., Conclusions: OAGB may be performed safely and with promising efficacy as both a primary and a revisional bariatric surgery, and it offers excellent resolution of diabetes., (Copyright © 2018 American Society for Bariatric Surgery. Published by Elsevier Inc. All rights reserved.)

Objective: Although the laparoscopic sleeve gastrectomy (SG) is increasingly performed for morbid obesity, gastric bypass is still considered by many to be the gold standard procedure for obese diabetic patients. The aim of this study was to assess the long-term results of SG in morbidly obese patients with type 2 diabetes., Methods: Diabetic patients who underwent SG at a single center between 2009 and 2011 were included. Outcomes assessed included postoperative complications, weight loss, and resolution or improvement in co-morbidities with an emphasis on diabetes, including glycated hemoglobin (HbA1C) and medication status., Results: Fifty-one diabetic patients underwent SG, 35 females and 16 males, with a collective mean age of 49 years and a mean body mass index of 43.2 kg/m 2 . On average, patients had had diabetes for 5.4 ± 7.3 years before surgery. Mean HbA1C and fasting glucose levels were 7.9 ± 1.6% and 166.9 ± 63 mg/dL, respectively. Eleven patients (22%) were insulin dependent at the time of surgery. Average body mass index at a mean follow-up of 5 years after surgery was 34.4 ± 5.8 kg/m 2 , with an average HbA1C of 6.6 ± 1% and an average fasting glucose of 123 ± 60 mg/dL. Only 3 patients remained insulin dependent., Conclusion: SG offers retainable weight loss results, accompanied by longstanding resolution or improvement of diabetes. Prospective, randomized controlled studies are warranted to better compare long-term outcomes between SG and gastric bypass., (Copyright © 2017 American Society for Bariatric Surgery. Published by Elsevier Inc. All rights reserved.)

Background: One-anastomosis gastric bypass (OAGB) is a promising laparoscopic procedure with various benefits including shorter operating times and less operative complications. That said, it is yet to gain widespread acceptance. Here, we describe our first-year experience with OAGB in our department, in particular the safety and efficacy of this procedure., Methods: This study is a retrospective analysis of all patients who underwent OAGB between March 2015 and March 2016 by our bariatric surgery unit. Patient demographics, comorbidities, operative and postoperative data were collected and analyzed as well as outcomes during the first year., Results: Four hundred and seven patients underwent OAGB (254 females, average age 41.8 ± 12.05, BMI = 41.7 ± 5.77 kg/m 2 ). Ninety-eight patients (24%) had prior bariatric surgery. Ninety-four patients (23%) had diabetes, 93 patients (22.8%) had hypertension, 123 (28.8%) had hyperlipidemia, and 35 patients (8.6%) suffered from obstructive sleep apnea. Eight patients (1.96%) had early minor complications (Clavien-Dindo 1-3a), and 10 patients (2.45%) suffered early major complications (Clavien-Dindo ≥3b). The average length of hospital stay was 2.2 ± 0.84 days (range 2-10 days). Twenty patients (4.8%) were readmitted, and 10 patients underwent reoperation. Patients who had had previous bariatric surgery had higher rates of complications, a prolonged hospital admission, higher rates of readmission, and early reoperations. The average excess weight loss (%EWL) 1 year following surgery was 88.9 ± 27.3 and 72.8 ± 43.5% in patients that underwent primary and revision OAGB, respectively., Conclusions: OAGB is both safe and effective as a primary as well as a revision bariatric surgery.

Background: Although considered a common bariatric procedure, laparoscopic adjustable gastric banding (LAGB) is associated with high rates of weight loss failure and long-term complications., Purpose: The purpose of this study was to re-assess the safety and outcome of conversion of failed LAGB to laparoscopic sleeve gastrectomy (LSG)., Materials and Methods: One hundred and nine patients underwent conversion from LAGB to LSG (78 females, mean age 43 ± 11.3 years, mean BMI 42.4 ± 7.4 kg/m 2 ). Patient demographics, obesity-related co-morbidities, BMI before and after the procedure, post-operative complications, and length of hospital stay were documented., Results: All cases were completed laproscopically, with 88% (n = 96) performed in a single stage. Fourteen patients developed early post-operative complications (12.8%), including two leaks and three post-operative bleeding. There were no mortalities in this series. Average BMI at least 1-year following surgery was 33 ± 5.3 kg/m 2 (excess weight loss (EWL) = 53.7%)., Conclusions: Our data suggests that conversion of failed LAGB to LSG is both safe and effective. Randomized controlled studies comparing conversion of a failed LAGB to sleeve gastrectomy versus other bariatric operations are necessary to clarify the optimal conversion procedure.

Glioblastoma multiforme is the most common and aggressive primary brain tumor in adults. A mesenchymal phenotype was associated with tumor aggressiveness and poor prognosis in glioblastoma multiforme patients. Recently, the transcription factor RUNX1 was suggested as a driver of the glioblastoma multiforme mesenchymal gene expression signature; however, its independent role in this process is yet to be described. Here, we assessed the role of RUNX1 in U87 glioblastoma multiforme cells in correspondence to its mediated transcriptome and genome-wide occupancy pattern. Overexpression of RUNX1 led to diminished tumor growth in nude and severe combined immunodeficiency mouse xenograft tumor model. At the molecular level, RUNX1 occupied thousands of genomic regions and regulated the expression of hundreds of target genes, both directly and indirectly. RUNX1 occupied genomic regions that corresponded to genes that were shown to play a role in brain tumor progression and angiogenesis and upon overexpression led to a substantial down-regulation of their expression level. When overexpressed in U87 glioblastoma multiforme cells, RUNX1 down-regulated key pathways in glioblastoma multiforme progression including epithelial to mesenchymal transition, MTORC1 signaling, hypoxia-induced signaling, and TNFa signaling via NFkB. Moreover, master regulators of the glioblastoma multiforme mesenchymal phenotype including CEBPb, ZNF238, and FOSL2 were directly regulated by RUNX1. The data suggest a central role for RUNX1 as master regulator of gene expression in the U87 glioblastoma multiforme cell line and mark RUNX1 as a potential target for novel future therapies for glioblastoma multiforme.

Background: Endoscopic retrograde cholangiopancreatography-induced perforation (EP) is a rare but severe complication. We describe the risk factors, management, and outcome of ERCP-induced perforations in a tertiary center., Methods: This is a case-control study. All EP cases between March 2004 and February 2015 were compared to a control group without perforation. Data on patients, procedures, presentation, perforation type, radiologic findings, management, and outcome were assessed., Results: Of 6,934 endoscopic retrograde cholangiopancreatographies, 37 patients (0.53%) had EP. Independent risk factors included failure of cannulation, a procedure described as "difficult," performing a precut and resection of a periampullary adenoma. Perforation was diagnosed during the procedure in 7 patients (19%). Median interval for diagnosis was 11 hours (range: 0-201 hours), with 84% diagnosed within 30 hours. The periampullary region was the most common EP site (51%). Twenty-nine patients (78%) were managed conservatively and 8 (22%) were operated. Three patients failed conservative management and required delayed operation. Failure of conservative management had a detrimental effect on morbidity and duration of stay. All patients who required operative intervention had perforation of either the duodenal free wall or the periampullary region., Conclusion: Clear risk factors can be used to raise suspicion of EP. Early diagnosis and management are critical for better outcome. This is especially important when operative intervention is indicated. Nonetheless, the majority of patients may be managed conservatively., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Although laparoscopic distal pancreatectomy (LDP) is gradually recognized as a safe and effective alternative to open distal pancreatectomy (ODP), it is not yet widely accepted., Objective: We describe our experience, with emphasis on the learning curve of LDP., Methods: Patients who underwent distal pancreatectomy (DP) between January 2011 and August 2014 were included. Operative and postoperative parameters, as well as pathology reports were evaluated., Results: Thirty-nine and 41 patients underwent LDP and ODP, respectively. The mean age and gender distribution were comparable between groups. In six patients (15.4%), a conversion to open surgery was indicated. Operating time and intraoperative blood transfusion rates were comparable between groups. One patient of the LDP group died postoperatively. Postoperative complications were comparable with similar Dindo-Clavien (DC) score. Length of stay (LOS) was shorter following LDP (8.15 ± 4.68 versus 11.3 ± 6.3 days, P = .014). Patients selected to have LDP had larger lesions compared to those who underwent ODP (4.59 ± 4.23 versus 3 ± 2.52 cm, respectively, P = .048). R0 resection rates between the groups were comparable (92.3% in LDP versus 97.5% in ODP) as well as lymph node (LN) harvest (6.4 ± 6.4 LN in LDP versus 7.6 ± 6.6 LN in ODP). Following the 17th patient, LDP operative time decreased by more than 35 minutes, no conversions were done, no blood transfusion was needed, and the LOS was shortened by over 2 days., Conclusions: Short learning curve, shorter LOS, and satisfactory short-term oncological outcome place LDP as an attractive alternative for selected patients requiring DP.

Background and Objectives: Liver resection of colorectal liver metastasis (CRLM) may necessitate large metabolic and physiologic reserve. As the population ages, resection of CRLM is increasingly required in the elderly. We assessed the safety and efficacy of these operations., Methods: Between February 2010 and 2015, 174 patients underwent liver resection of CRLM. Fifty-four and 120 patients were over and under the age of 70 at the time of surgery, respectively (mean ages: 76 ± 4 and 56.5 ± 9 years). Patient and tumor characteristics, perioperative, and long-term outcomes were compared., Results: Elderly patients had increased rates of IHD (18.5% versus 6.6%, P = 0.0002), COPD (9.2% versus 4.1%, P = 0.01), and DM (30% versus 14%, P = 0.02). Operative time was shorter in elderly patients (222 ± 109 versus 261 ± 110 min; P = 0.04). Intraoperative blood loss was comparable. The rate of minor postoperative complications was similar between groups, but elderly patients had higher rate of major complications (11.1% versus 2.5%, P < 0.0001). One elderly patient died following surgery (1.8%). Length of hospital stay was similar between groups. No difference in 3-year survival was demonstrated., Conclusions: Although associated with a small increase in postoperative morbidity and mortality, liver resection may be performed safely and effectively in carefully selected elderly patients. J. Surg. Oncol. 2016;113:485-488. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

Background: Ependymomas are the most common glial neoplasms in the spinal cord. However, spinal cord ependymomas presenting with regional dissemination along the neuroaxis are rare, with a yet undetermined standard of care. We retrospectively evaluated the management and outcomes of patients who were diagnosed with spinal ependymoma with regional metastases at presentation (SERMP)., Methods: Between 2002 and 2012, 16 patients with regionally metastatic spinal ependymomas were diagnosed and treated. The patients were retrospectively divided into two groups according to tumor grading and histological features. Nine patients were diagnosed with myxopapillary ependymomas (MPE), and seven patients were diagnosed with other low-grade ependymomas., Results: With a median follow-up of 46.4 months, 13 out of 16 patients had no postsurgical recurrence/progression of the disease. In three patients, the disease recurred/progressed, leading to death in one patient. There was no correlation between gross total removal (GTR) of the main tumor, or resection of the main lesion and the metastatic foci and increased progression free survival in patients of the MPE group. There was an advantage for patients diagnosed with other low-grade ependymomas. Adjuvant radiotherapy did not prove beneficial., Conclusions: SERMP has a relatively benign course. Achieving GTR of both the main lesion and the metastases is preferable, but should not be achieved at any cost, especially in MPE interfering with the conus medullaris. The benefit of adjuvant radiotherapy remains unproven.

Endometriosis is a common condition associated with pelvic pain and infertility. This study group has previously shown that supplementation of dendritic cells led to enhancement of endometriosis lesion growth and angiogenesis. This study determined whether endometriosis is dependent on the presence of endogenous dendritic cells. Surgical induction of endometriosis was performed in CD11c⁺ DTR/GFP transgenic (Tg) female mice in which dendritic cells were ablated upon injection of diphtheria toxin (DT). Mice were allocated into four groups (n=5 each): group I, wild-type mice treated with vehicle; group II, wild-type mice treated with DT; group III, Tg mice treated with DT; and group IV, Tg mice treated with vehicle. After 10 days, mice were killed and endometriosis lesions were analysed by flow cytometry. DT treatment led to ablation of dendritic cells in spleens and endometriosis lesions in Tg mice while no ablation was observed in controls. Corresponding to dendritic cell ablation, endometriosis lesions in group III were ∼5-fold smaller than in the control groups (ANOVA P<0.0001). This study suggests that endometriosis development is dependent on the presence of endogenous dendritic cells. Therapies designed to inhibit dendritic cell infiltration as possible treatments for endometriosis warrant further study., (Copyright © 2014 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)