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Introduction Recently, there has been increasing interest in the preoperative prediction and prevention of post-hepatectomy liver failure (PHLF). This is a particular concern in colorectal liver metastases (CRLM), when surgery follows potentially hepatotoxic chemotherapy. Platelet-based liver scores (PBLS) such as APRI and FIB-4 are predictive of chemotherapy-associated liver injury (CALI) and PHLF. Estimation of the future liver remnant function (eFLRF) by combining 99m Tc-Mebrofenin Hepatobiliary Scintigraphy (HBS BSA ) with future liver remnant volume ratio (FLRV%), is predictive of PHLF and related mortality. We hypothesized that a HBS BSA based formula was a better predictor for PHLF than PBLS in chemotherapy-pretreated CRLM. Methods Between 2012 and 2016, 140 patients underwent liver resection for CRLM following systemic therapy. HBS BSA , FLRV%, eFLRF and PBLS were calculated and compared for their value in predicting PHLF. Results eFLRF and FLRV% had a better predictive value for PHLF than HBS BSA alone and APRI and FIB-4 (AUC = 0.800, 0.843 versus 0.652, 0.635 and 0.658 respectively). In a subgroup analysis (Oxaliplatin all, Oxaliplatin ≥ 6 cycles, Irinotecan all and Irinotecan ≥ 6 cycles), eFLRF was the only factor predictive for PHLF in all subgroups (all: p ≤ 0.05). Prediction of HBS BSA for chemotherapy associated steato-hepatitis (CASH) reached almost significance (p = 0.06). FIB-4 was predictive for sinusoidal obstruction syndrome (SOS) (p = 0.011). Only weak correlation was found between HBS BSA and PBLS. Conclusion eFLRF is a better predictor of PHLF than PBLS or HBS BSA alone. PBLS seem to measure other aspects of liver function or damage than HBS BSA . [ABSTRACT FROM AUTHOR]

Analyzes the infrared and Raman spectra of 2,3-diketopiperazine molecule in the solid state. Minimum energy conformer of 2,3-diketopiperazine; Vibrational spectra in solution and in the solid state; Differences in the molecular geometry in the gas phase and crystalline state.

Analyzes the solid structure of 2,3-diketopiperazine, a cyclic oxamide, on the basis of X-ray diffraction. Variations in the measuring strategy; Relation between the size of the background error and the nearby Bragg intensity; Strategy to decrease the error margins typical for larger intensities.

Background Donor-related malignancy is a rare complication of organ transplantation. Methods In this case series, we discuss three cases of donor-related cancers in kidney transplant recipients who were registered in our center between 1979 and 2015. They account for an incidence of 0.29% of donor-related malignancies of a total of 1015 transplanted kidney grafts (deceased and living donors). The three cases that we describe presented in different ways and with different severity, although the response to the initiated treatment was comparable. Results All three patients not only survived their cancer episode but also had a complete oncological remission and underwent successful second kidney transplantation, accounting for a 100% survival rate in our small cohort. Conclusions Despite the very low incidence of this complication, transplant clinicians must be aware of the occurrence of donor-related malignancies when selecting a donor and should be able to diagnose and treat a case of donor-related cancer. [ABSTRACT FROM AUTHOR]

Estimation of the future liver remnant function (eFLRF) in a formula combining 99mTc-Mebrofenin Hepatobiliary Scintigraphy (HBS) and FLRV% liver volumetry has been shown to predict PHLF. B Methods: b Estimation of the future liver remnant function (eFLRF) was performed in 140 patients prior to liver resection for colorectal liver metastasis after preoperative systemic therapy. [Extracted from the article]

Background: For many patients with resected epidermal growth factor receptor mutation-positive (EGFRm) non-small cell lung cancer (NSCLC), current standard of care (SoC) is adjuvant chemotherapy; however, disease recurrence remains high. Based on positive results from ADAURA (NCT02511106), adjuvant osimertinib was approved for treatment of resected stage IB‒IIIA EGFRm NSCLC., Objective: The aim was to assess the cost-effectiveness of adjuvant osimertinib in patients with resected EGFRm NSCLC., Methods: A five-health-state, state-transition model with time dependency was developed to estimate lifetime (38 years) costs and survival of resected EGFRm patients treated with adjuvant osimertinib or placebo (active surveillance), with/without prior adjuvant chemotherapy, using a Canadian Public Healthcare perspective. Transitions between health states were modeled using ADAURA and FLAURA (NCT02296125) data, Canadian life tables, and real-world data (CancerLinQ Discovery ® ). The model used a 'cure' assumption: patients remaining disease free for 5 years after treatment completion for resectable disease were deemed 'cured.' Health state utility values and healthcare resource usage estimates were derived from Canadian real-world evidence., Results: In the reference case, adjuvant osimertinib treatment led to a mean 3.20 additional quality-adjusted life-years (QALYs; (11.77 vs 8.57) per patient, versus active surveillance. The modeled median percentage of patients alive at 10 years was 62.5% versus 39.3%, respectively. Osimertinib was associated with mean added costs of Canadian dollars (C$)114,513 per patient and a cost/QALY (incremental cost-effectiveness ratio) of C$35,811 versus active surveillance. Model robustness was demonstrated by scenario analyses., Conclusions: In this cost-effectiveness assessment, adjuvant osimertinib was cost-effective compared with active surveillance for patients with completely resected stage IB‒IIIA EGFRm NSCLC after SoC., (© 2023. The Author(s).)

Background: Hepatectomy remains the most important treatment modality for most malignant liver tumors. Vascular involvement stays a reason for unresectability or major parenchymal resection. A possible way to avoid this is parenchymal-sparing hepatectomy (PSHX) with vascular resection and reconstruction (HVRR). In this article, we aim to demonstrate the specific role of this technique in avoiding post-hepatectomy liver failure (PHLF)., Methods: A retrospective analysis of 10 patients who underwent HVRR was conducted. 99m Technetium-mebrofenin hepatobiliary scintigraphy (HBS) was used to predict the future liver remnant function (FLRF). Calculations were made for each patient to compare HVRR and major hepatectomy (with or without portal vein embolization)., Results: In our cohort, there was no perioperative mortality. Two patients suffered a Clavien-Dindo grade 3a complication and none had clinically significant PHLF. Estimated FLRF was significantly higher in HVRR compared to major hepatectomy after portal vein embolization ( p  < .005)., Conclusions: Instead of focusing on inducing liver remnant hypertrophy, preserving parenchyma through HVRR can be an interesting treatment strategy. It can be performed with an acceptable operative risk. Calculations of FLRF (using HBS) suggest that this approach is able to reduce the risk for PHLF and related morbidity or mortality.

Purpose: Mixed reality (MR) for image-guided surgery may enable unobtrusive solutions for precision surgery. To display preoperative treatment plans at the correct physical position, it is essential to spatially align it with the patient intra-operatively. Accurate alignment is safety critical because it will guide treatment, but cannot always be achieved for varied reasons. Effective visualization mechanisms that reveal misalignment are crucial to prevent adverse surgical outcomes to ensure safe execution., Methods: We test the effectiveness of three MR visualization paradigms in revealing spatial misalignment: wireframe, silhouette, and heatmap, which encodes residual registration error. We conduct a user study among 12 participants and use an anthropomorphic phantom mimicking total shoulder arthroplasty. Participants wearing Microsoft HoloLens 2 are presented with 36 randomly ordered spatial (mis)alignments of a virtual glenoid model overlaid on the phantom, each rendered using one of the three methods. Users choose whether to accept or reject the spatial alignment at every trial. Upon completion, participants report their perceived difficulty while using the visualization paradigms., Results: Across all visualization paradigms, the ability of participants to reliably judge the accuracy of spatial alignment was moderate (58.33%).The three visualization paradigms showed comparable performance. However, the heatmap-based visualization resulted in significantly better detectability than random chance ([Formula: see text]). Despite heatmap enabling the most accurate decisions according to our measurements, wireframe was the most liked paradigm (50 %), followed by silhouette (41.7 %) and heatmap (8.3 %)., Conclusion: Our findings suggest that conventional mixed reality visualization paradigms are not sufficiently effective in enabling users to differentiate between accurate and inaccurate spatial alignment of virtual content to the environment., (© 2022. CARS.)

Background: Information about the impact of respiratory syncytial virus (RSV) on quality of life in older adults is limited. This study characterized the patient experience of RSV illness in USA older adults and assessed the content validity of the InFLUenza Patient Reported Outcome (FLU-PRO) in this population., Methods: This qualitative, non-interventional, cross-sectional study included hybrid concept elicitation and cognitive debriefing interviews with 30 individuals (age ≥50 years) with polymerase chain reaction-confirmed RSV diagnosed within 6 months of screening. Targeted literature review was first conducted to inform the development of interview materials. Webcam or telephone interviews were conducted by qualitative researchers using a semistructured interview guide. Interview transcripts were coded and analyzed using Excel and NVivo software., Results: All participants reported impacts on daily activities, social activities, and relationships during RSV disease. Physical functioning was impaired in 25 (83%) participants, and 18 (60%) reported not engaging in leisure activities/hobbies. All nine participants who were working reported major impacts on work. Most (n = 28; 93%) described emotional impacts. A majority (n = 19; 63%) reported symptoms lasting beyond the acute disease stage from a week to >1 month. Symptom concepts reported generally matched FLU-PRO items and domains. Cognitive debriefing indicated that FLU-PRO was easy to understand and captured participants' experiences of RSV illness., Conclusions: This study indicates that RSV disease in adults aged ≥50 years in the USA has substantial impacts on daily life and that the concepts included in FLU-PRO are appropriate and fit for purpose as a measure of RSV symptoms in this population., (© 2021 GlaxoSmithKline Pharmaceuticals S.A. Influenza and Other Respiratory Viruses published by John Wiley & Sons Ltd.)

Background: Since patient survival after kidney transplantation is significantly improved with a shorter time on dialysis, it is recommended to start the transplant workup in a timely fashion., Methods: This retrospective study analyses the chronology of actions taken during the care for patients with chronic kidney disease (CKD) stage 5 who were waitlisted for a first kidney transplant at the Antwerp University Hospital between 2016 and 2019. We aimed to identify risk factors for a delayed start of the transplant workup (i.e. after dialysis initiation) and factors that prolong its duration., Results: Of the 161 patients included, only 43% started the transplant workup before starting dialysis. We identified the number of hospitalization days {odds ratio [OR] 0.79 [95% confidence interval (CI) 0.69-0.89]; P < 0.001}, language barriers [OR 0.20 (95% CI 0.06-0.61); P = 0.005] and a shorter nephrology follow-up before CKD stage 5 [OR 0.99 (95% CI 1.0-0.98); P = 0.034] as factors having a significant negative impact on the probability of starting the transplant screening before dialysis. The workup took a median of 8.6 months (interquartile range 5-14) to complete. The number of hospitalization days significantly prolonged its duration., Conclusion: The transplant workup was often started too late and the time needed to complete it was surprisingly long. By starting the transplant workup in a timely fashion and reducing the time spent on the screening examinations, we should be able to register patients on the waiting list before or at least at the start of dialysis. We believe that such an internal audit could be of value for every transplant centre., (© The Author(s) 2022. Published by Oxford University Press on behalf of the ERA.)

Background: Delayed graft function (DGF) remains a clinically relevant problem in the post-transplant period, especially in patients with a renal graft from a "donation after cardiac death" (DCD) donor. Controversy exists around the optimal perioperative fluid therapy in such patients. These patients may benefit from a perioperative saline loading fluid protocol, which may reduce the risk of DGF., Methods: We compared 2 cohorts of patients who underwent a renal transplantation with a graft from a DCD donor. From January 2003 until December 2012, patients (N = 46) were hemodynamically managed at the discretion of the care-giving physician, without a preoperative fluid administration protocol (first study period). From January 2015 until March 2019 (N = 26), patients received saline loading before, during, and after kidney transplantation according to a well-defined saline loading fluid protocol (second study period). The relationship between the use of this perioperative fluid protocol and DGF was analyzed using univariable and multivariable logistic regression models., Results: DGF occurred in 11 of 46 (24%) patients in the first study period and in 1 of 26 (4%) in the second study period (P < .05). In a multivariable model, correcting for cold ischemia time and Kidney Donor Risk Index, the use of a saline loading fluid protocol in the perioperative phase was nearly significantly associated with a decrease in DGF (P = .07)., Conclusion: In our DCD transplant population, DGF rates were low. Our data further strongly suggest that implementation of a perioperative saline loading fluid protocol was independently associated with a lower risk of DGF., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Hemodialysis-related portosystemic encephalopathy (HRPSE) is a clinical phenomenon where portosystemic encephalopathy (PSE) develops without liver dysfunction, usually caused by changes in the portosystemic blood flow related to hemodialysis. We describe the case of a 22-year old patient with a transjugular intrahepatic portosystemic shunt (TIPS) who developed HRPSE several months after initiation of hemodialysis. Despite initial therapy with laxatives and neomycin symptoms recurred. It was only after relocation of the hemodialysis catheter from the superior caval vein to the femoral vein that symptoms completely resolved.

Aim: Pancreaticopleural fistula (PPF) is a rare complication of acute or chronic pancreatitis. When the pancreatic duct disrupts, pancreatic fluid may leak into the retroperitoneum and fistulate into the pleural cavity. Patients usually present with thoracic complaints, making it hard to suspect an abdominal etiology. Although PPF is uncommon, one must consider this diagnosis in patients with thoracic complaints and a history of alcohol abuse or pancreatitis. Methods: We present an illustrative case and review of the literature on PPF. Results: A 47-year old man was presented with recurrent PPF due to pancreas divisum, pancreatic stones and chronic exudative pancreatitis, resulting in unilateral empyema. After initial conservative treatment, operative measures were needed. We report omentoplasty against the diaphragmatic hiatus in combination with VATS (video-assisted thoracoscopic surgery) thoracotomy with decortication and debridement as a feasible operative option for resolving PPF. Conclusion: PPF is a rare complication of pancreatitis. The diagnosis is difficult to make and can be confirmed by thoracocentesis and proper imaging, preferably MRCP. Treatment options include conservative, endoscopic (ERCP) or surgical measures. Omentoplasty positioned against the diaphragmatic hiatus is a feasible technique for closure of PPF.

Introduction: The incidence of herpes zoster (HZ) rises steeply after the age of 50 years and the number of HZ cases and complications such as postherpetic neuralgia (PHN) is predicted to increase because of the ageing population. The objective of this study was to estimate the cost-effectiveness of recombinant zoster vaccine (RZV) compared with no vaccine for the Japanese population aged ≥ 65 years., Methods: A multi-cohort static Markov model with a cycle length of 1 year was used to follow a hypothetical cohort of 1 million people aged ≥ 65 years over their remaining lifetime. Vaccination at ≥ 65 years was used in alignment with the influenza and pneumococcal vaccines recommended from 65 years. Japan-specific data inputs for the model were obtained from local data sources. Age-stratified vaccine efficacy and waning rates were based on published clinical trial data. In the base-case analysis, vaccine coverage was assumed to be 40% with a second dose compliance of 95%. Costs and outcomes were discounted at 2% annually and the incremental cost-effectiveness ratio (ICER) was calculated from both a payer's and the societal perspective. Sensitivity analyses were carried out to explore the overall uncertainty in the model., Results: Vaccination with RZV was projected to prevent 48,943 HZ cases and 12,136 PHN cases per million people aged ≥ 65 years compared with no vaccination. The incremental costs and quality-adjusted life years (QALYs) gained were ¥9.99 billion and 2314 QALYs from a payer's perspective and ¥9.34 billion and 2314 QALYs from a societal perspective. The resulting ICERs were approximately ¥4,320,000 and ¥4,040,000 per QALY gained from a payer's and the societal perspective, respectively. The ICER remained below a willingness-to-pay threshold of ¥5,000,000 for most sensitivity analyses carried out., Conclusion: Vaccination against HZ with RZV would be cost-effective compared with no vaccination for the Japanese population aged ≥ 65 years., Trial Registration: GSK study identifier: HO-16-17837., Funding: GlaxoSmithKline Biologicals SA.

Objectives: In 2013, the herpes zoster (HZ) immunisation programme was introduced in the UK, recommending vaccination of adults 70 years of age (YOA) with the zoster vaccine live (ZVL), the only vaccine available at the time. The recently approved adjuvanted recombinant zoster vaccine (RZV) has a substantially different clinical profile that may offer additional benefits.This study aimed to 1) assess the public health impact (PHI) of introducing RZV in the UK compared with the current vaccination strategy and 2) explore via scenario analyses the optimal age group of vaccination in terms of PHI., Design: A previously developed health economic model was adapted to the UK setting., Setting: Calculations were based on efficacy data from pivotal clinical trials, HZ incidence and postherpetic neuralgia (PHN) probability from a UK study and HZ-associated complication rates from published literature., Population: The base-case population considered a 2018-projected UK vaccination cohort of individuals 70 YOA., Interventions: Vaccination with ZVL or RZV, assuming a first-dose coverage of 48.3% for both vaccines and 70% compliance for the second dose of RZV., Outcome Measures: Outcomes included reduction of HZ and PHN cases, complications and the use of healthcare resources over a life-time horizon. The impact of coverage and second-dose compliance was also explored., Results: Compared with no vaccination, RZV would lead to a reduction of 30 262 HZ and 5409 PHN cases while ZVL would lead to a reduction of 7909 HZ and 3567 PHN cases. The number needed to vaccinate to prevent 1 HZ case is 12 with RZV and 45 with ZVL. The highest PHI with RZV could be achieved in individuals 60 or 65 YOA., Conclusion: Under the model assumptions, RZV is predicted to avert more HZ and PHN cases compared with ZVL. Results were robust under different scenario and sensitivity analyses., Competing Interests: Competing interests: DVO, MH, BB, DC and HSC are employees of the GSK group of companies. MH, DC and HSC hold shares in the GSK group of companies. SL is a freelance consultant working on behalf of the GSK group of companies., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background/objectives: Studies reporting on function after pancreatic surgery are frequently based on diabetes history, fasting glycemia or random glycemia. The aim of this study was to investigate prospectively the evolution of pancreatic function in patients undergoing pancreaticoduodenectomy based on proper pre- and postoperative function tests. It was hypothesised that pancreatic function deteriorates after pancreaticoduodenectomy., Methods: Between 2013 and 2016, 78 patients undergoing pancreaticoduodenectomy for oncologic indications had a prospective evaluation of their endocrine and exocrine pancreatic function. Endocrine function was evaluated with the 75 g oral glucose tolerance test (OGTT) and the 1 mg intravenous glucagon test. Exocrine function was evaluated with a 13C-labelled mixed-triglyceride breath test. Tests were performed pre- and postoperatively., Results: In 90.5% (19/21) of patients with preoperatively known diabetes, no change in endocrine function was observed. In contrast, endocrine function improved in 68.1% (15/22) of patients with newly diagnosed diabetes. 40% (14/35) of patients with a preoperative normal OGTT or prediabetes experienced deterioration in function. In multivariate analysis, improvement of newly diagnosed diabetes was correlated with preoperative bilirubin levels (p = 0.045), while progression towards diabetes was correlated with preoperative C-peptidogenic index T 30 (p = 0.037). A total of 20.5% (16/78) of patients had pancreatic exocrine insufficiency preoperatively. Another 51.3% (40/78) of patients deteriorated on exocrine level. In total, 64.1% (50/78) of patients required pancreatic enzyme-replacement therapy postoperatively., Conclusions: Although deterioration of endocrine function was expected after pancreatic resection, improvement is frequently observed in patients with newly diagnosed diabetes. Exocrine function deteriorates after pancreaticoduodenectomy., (Copyright © 2017 IAP and EPC. Published by Elsevier B.V. All rights reserved.)

Background: The Kidney Donor Risk Index (KDRI) is a quantitative evaluation of the quality of donor organs and is implemented in the US allocation system. This single-centre study investigates whether the implementation of the KDRI in our decision-making process to accept or decline an offered deceased donor kidney, increases our acceptance rate., Methods: From April 2015 until December 2016, we prospectively calculated the KDRI for all deceased donor kidney offers allocated by Eurotransplant to our centre. The number of the transplanted versus declined kidney offers during the study period were compared to a historical set of donor kidney offers., Results: After implementation of the KDRI, 26.1% (75/288) of all offered donor kidneys were transplanted, compared with 20.7% (136/657) in the previous period (P < 0.001). The median KDRI of all transplanted donor kidneys during the second period was 0.97 [Kidney Donor Profile Index (KDPI) 47%], a value significantly higher than the median KDRI of 0.85 (KDPI 34%) during the first period (P = 0.047). A total of 68% of patients for whom a first-offered donor kidney was declined during this period were transplanted after a median waiting time of 386 days, mostly with a lower KDRI donor kidney., Conclusions: Implementing the KDRI in our decision-making process increased the transplantation rate by 26%. The KDRI can be a supportive tool when considering whether to accept or decline a deceased donor kidney offer. More data are needed to validate this score in other European centres., (© The Author 2017. Published by Oxford University Press on behalf of ERA-EDTA.)

Aim: To compare the performance of 3 published delayed graft function (DGF) calculators that compute the theoretical risk of DGF for each patient., Methods: This single-center, retrospective study included 247 consecutive kidney transplants from a deceased donor. These kidney transplantations were performed at our institution between January 2003 and December 2012. We compared the occurrence of observed DGF in our cohort with the predicted DGF according to three different published calculators. The accuracy of the calculators was evaluated by means of the c-index (receiver operating characteristic curve)., Results: DGF occurred in 15.3% of the transplants under study. The c index of the Irish calculator provided an area under the curve (AUC) of 0.69 indicating an acceptable level of prediction, in contrast to the poor performance of the Jeldres nomogram (AUC = 0.54) and the Chapal nomogram (AUC = 0.51). With the Irish algorithm the predicted DGF risk and the observed DGF probabilities were close. The mean calculated DGF risk was significantly different between DGF-positive and DGF-negative subjects ( P < 0.0001). However, at the level of the individual patient the calculated risk of DGF overlapped very widely with ranges from 10% to 51% for recipients with DGF and from 4% to 56% for those without DGF. The sensitivity, specificity and positive predictive value of a calculated DGF risk ≥ 30% with the Irish nomogram were 32%, 91% and 38%., Conclusion: Predictive models for DGF after kidney transplantation are performant in the population in which they were derived, but less so in external validations., Competing Interests: Conflict-of-interest statement: This project was an investigator driven study without any support from external organizations. The authors have no conflict of interest.

Background and Aims: Due to the shortage of donor livers, minor ABO-incompatible liver transplantations are commonly performed. Together with the allograft, immunocompetent B-lymphocytes, called passenger lymphocytes, are transplanted. In case of minor ABO-incompatibility, these passenger lymphocytes produce antibodies directed towards the recipient's red blood cells, which causes immune-mediated hemolysis, also known as the passenger lymphocyte syndrome (PLS). Although this is a self-limiting disorder, serious complications can occur, including graft failure. Retrospectively, we evaluated the role of PLS in minor ABO-incompatible liver transplantations performed at our center. Methods: A retrospective analysis was conducted for all minor ABO-incompatible liver transplantations performed at the Antwerp University Hospital between 2003 and 2015. All patient files were inspected for clinical and laboratory findings. In cases of PLS diagnosis, the applied treatment was also studied. Results: In total, 10 patients underwent a minor ABO-incompatible liver transplantation and 4 showed signs of PLS. All 4 PLS patients were treated with different therapeutic strategy, corresponding to the severity of hemolysis. In all 4 cases, PLS resolved following treatment. Conclusion: When performing minor ABO-incompatible liver transplantations, knowledge of PLS is elemental. Next to a high index of clinical suspicion, we suggest routine screening for markers of hemolysis, with emphasis on haptoglobin level and direct antiglobulin test, weekly in the first 4 weeks post-transplantation as well as in case of a sudden hemoglobin drop within the first 3 months after transplantation. Peri- and postoperative transfusion support using donor-compatible blood has been suggested to prevent the occurrence or limit the extent of hemolysis., Competing Interests: The authors have no conflict of interests related to this publication.

Background: Estimation of the future liver remnant function (eFLRF) can avoid post-hepatectomy liver failure (PHLF). In a previous study, a cutoff value of 2.3%/min/m 2 for eFLRF was a better predictor of PHLF than future liver remnant volume (FLRV%). In this prospective interventional study, investigating a management strategy aimed at avoiding PHLF, this cutoff value was the sole criterion assessing eligibility for hepatectomy, with or without portal vein occlusion (PVO)., Methods: In 100 consecutive patients, eFLRF was determined using the formula: eFLRF = FLRV% × total liver function (TLF). Group 1 (eFLRF >2.3%/min/m 2 ) underwent hepatectomy without preoperative intervention. Group 2 (eFLRF <2.3%/min/m 2 ) underwent PVO and re-evaluation of eFLRF at 4-6 weeks. Hepatectomy was performed if eFLRF had increased to >2.3%/min/m 2 , but was considered contraindicated if the value remained lower., Results: In group 1 (n = 93), 1 patient developed grade B PHLF. In group 2 (n = 7) no PHLF was recorded. Postoperative recovery of TLF in patients with preoperative eFLRF <2.3%/min/m 2 occurred more rapidly when PVO had been performed., Conclusion: A predefined cutoff for preoperatively calculated eFLRF can be used as a tool for selecting patients prior to hepatectomy, with or without PVO, thus avoiding PHLF and PHLF-related mortality., (Copyright © 2016 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Objective: Recently, pancreaticogastrostomy (PG) has attracted renewed interest as a reconstruction technique after pancreaticoduodenectomy (PD), as it may imply a lower risk of clinical pancreatic fistula than reconstruction by pancreaticojejunostomy (PJ). We hypothesise that pancreatic exocrine insufficiency (PEI) is more common during clinical follow-up after PG than it is after PJ., Research Design and Methods: This study compares the prevalence of PEI in patients undergoing PD for malignancy with reconstruction by PG versus reconstruction by PJ. PEI during the first year of follow-up was defined as the intake of pancreatic enzyme replacement therapy (PERT) within one year postoperatively and/or an abnormal exocrine function test., Results: A total of 186 patients, having undergone surgery at two university hospitals, were included in the study. PEI during the first year postoperatively was present in 75.0% of the patients with PG, compared to 45.7% with PJ (p < 0.001). Intake of PERT within one year after surgery was found to be more prevalent in the PG group, i.e. 75.8% versus 38.5% (p < 0.001). There was a trend towards more disturbed exocrine function tests after PG (p = 0.061)., Conclusions: PEI is more common with PG reconstruction than with PJ reconstruction after pancreaticoduodenectomy for malignancy., (Copyright © 2016 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Objective: Previous reports on the prevalence of diabetes in pancreatic cancer and chronic pancreatitis patients are based on inconsistent and equivocal criteria. The objective of this study is to prospectively assess with conclusive methods the preoperative glycaemic status of patients undergoing pancreatic surgery. We hypothesise that most of those patients are unaware of these disturbances in glycaemic status and that the prevalence is underestimated., Methods: During the last 2 years, patients referred for pancreatic surgery and without history of diabetes underwent a prospective preoperative screening with an oral glucose tolerance test (OGTT) and determination of the glycated haemoglobin level (HbA1c). The American Diabetes Association's criteria for diabetes and pre-diabetes were used. Beta-cell function and insulin sensitivity were calculated using HOMA2 indices. Impact on surgical policy has been scored., Results: 99 patients were screened, 25 had a history of diabetes. The other 74 underwent an OGTT and HbA1c determination. Only 29.7% (22/74) had a normal glucose metabolism, while 8.1% (6/74) had impaired fasting glucose, 21.6% (16/74) had impaired glucose tolerance, 6.7% (5/74) had a combination of both, and 33.8% (25/74) had undiagnosed diabetes. In 15.2% (15/99) of the patients, this preoperative assessment had an impact on surgical policy., Conclusions: 77.7% of patients referred for pancreatic surgery had some degree of (pre-)diabetes. In 70.3% of patients without a history of diabetes, these disturbances in glucose metabolism are a new finding. Physicians involved in pancreatic surgery should be aware of the frequently undiagnosed (pre-)diabetes and actively check for it. This prevalence is underestimated., (Copyright © 2016 IAP and EPC. Published by Elsevier B.V. All rights reserved.)

The murine, gonadotropic LbetaT2 cell line was assessed as a potential in vitro model to analyze estrogen receptor (ER)-mediated regulation of luteinizing hormone (LH) synthesis and secretion. In agreement with limited literature data, repeated exposure to (sub) physiological concentrations of gonadotropin-releasing hormone enhanced LHbeta-subunit gene expression, being the rate-limiting step of LH synthesis, and the corresponding LH secretory response. However, in the same subclone of the LbetaT2 cell line, we observed that LH production was not affected following exposure to E(2), which is in contrast to previously reported weak or modest effects. One explanation may be the absence of measurable ERalpha protein expression on the one hand and impaired ER signal transduction on the other. Furthermore, an alternative ERalpha mRNA splicing variant was detected in the LbetaT2 cell line, which (theoretically) encodes for a protein that may alter ERalpha transcriptional activity, depending on the cellular context. The studied LbetaT2 subclone did not show a generalized impairment of nuclear receptor function, as we observed androgen- and glucocorticoid-induced gene transcription, together with enhanced LH secretory response following dexamethasone treatment. Since its development, the gonadotropic LbetaT2 cell line served as a reference model to study gonadotroph-specific effects because of its mature properties. Nevertheless, this cell line does not seem to be a suitable in vitro model for the study of estrogenic regulatory effects at the level of the pituitary gonadotrophs in view of the unstable nature of ER signaling in LbetaT2 cells.

Signal transducer and activator of transcription (STAT) 3 is overexpressed or activated in most types of human tumors and has been classified as an oncogene. In the present study, we investigated the contribution of the STAT3s to the proinvasive activity of trefoil factors (TFF) and vascular endothelial growth factor (VEGF) in human colorectal cancer cells HCT8/S11 expressing VEGF receptors. Both intestinal trefoil peptide (TFF3) and VEGF, but not pS2 (TFF1), activate STAT3 signaling through Tyr(705) phosphorylation of both STAT3alpha and STAT3beta isoforms. Blockade of STAT3 signaling by STAT3beta, depletion of the STAT3alpha/beta isoforms by RNA interference, and pharmacologic inhibition of STAT3alpha/beta phosphorylation by cucurbitacin or STAT3 inhibitory peptide abrogates TFF- and VEGF-induced cellular invasion and reduces the growth of HCT8/S11 tumor xenografts in athymic mice. Differential gene expression analysis using DNA microarrays revealed that overexpression of STAT3beta down-regulates the VEGF receptors Flt-1, neuropilins 1 and 2, and the inhibitor of DNA binding/differentiation (Id-2) gene product involved in the neoplastic transformation. Taken together, our data suggest that TFF3 and the essential tumor angiogenesis regulator VEGF(165) exert potent proinvasive activity through STAT3 signaling in human colorectal cancer cells. We also validate new therapeutic strategies targeting STAT3 signaling by pharmacologic inhibitors and RNA interference for the treatment of colorectal cancer patients.