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Ido Zamberg,1,2 Julien Maillard,1,* Benjamin Assouline,1,* Simon Tomala,1 Gleicy Keli-Barcelos,1 Florence Aldenkortt,1 Thomas Mavrakanas,2,3 Axel Andres,2,4 Eduardo Schiffer1,2 1Division of Anesthesiology, Department of Anesthesiology, Clinical Pharmacology, Intensive Care and Emergency Medicine, Geneva University Hospitals, Geneva, Switzerland; 2Faculty of Medicine University of Geneva, Geneva, Switzerland; 3Department of Medicine, McGill University Health Centre, Montreal, QC, Canada; 4Division of Transplantation, Department of Surgery, University Hospitals of Geneva, Geneva, Switzerland*These authors contributed equally to this workCorrespondence: Eduardo SchifferDivision of Anesthesiology, Department of Anesthesiology, Clinical Pharmacology, Intensive Care and Emergency Medicine, Geneva University Hospitals, Rue Gabrielle-Perret-Gentil 4, Geneva, CH-1205, SwitzerlandTel +41 22 372 30 60Fax +41 22 372 76 90Email eduardo.schiffer@hcuge.chBackground & Aims: Hyponatremia is an important predictor of early death among cirrhotic patients in the orthotopic liver transplantation (OLT) waiting list. Evidence exists that prioritizing OLT waiting list according to the MELD score combined with plasma sodium concentration might prevent pre transplantation death. However, the evolution of plasma sodium concentrations during the perioperative period of OLT is not well known. We aimed to describe the evolution of perioperative sodium concentration during OLT and its relation to perioperative neurohormonal responses.Methods: Twenty-seven consecutive cirrhotic patients who underwent OLT were prospectively included in the study over a period of 27 months. We studied the evolution of plasma sodium levels, the hemodynamics, the neurohormonal response and other biological markers during the perioperative period of OLT.Results: Among study’s population, four patients had hyponatremia before OLT, all with Child cirrhosis. In patients with hyponatremia, plasmatic sodium reached normal levels during surgery, and sodium levels remained within normal ranges 1 day, 7 days, as well as 6 months after surgery for all patients. Creatinine clearance was decreased significantly during the perioperative period, while creatinine and cystatin C levels increased significantly. Neutrophil gelatinase-associated lipocalin (NGAL) and vasopressin levels did not change significantly in this period. Plasma renin activity, concentrations of norepinephrine and brain natriuretic peptide varied significantly during the perioperative period.Conclusion: In our study, plasmatic sodium concentrations among hyponatremic cirrhotic patients undergoing OLT seem to reach normal levels after OLT and remain stable six months after surgery providing more evidence for the importance of sodium levels in prioritization of liver transplant candidates. Further investigation of rapid correction and stabilization of sodium levels after OLT, as observed in our study, would be of interest in order to fully understand the mechanisms involved in cirrhosis-related hyponatremia, its prognostic value and clinical implications.Keywords: liver, transplantation, hyponatremia, cirrhosis, MELD score

Context The Igls criteria were developed to provide a consensus definition for outcomes of β-cell replacement therapy in the treatment of diabetes during a January 2017 workshop sponsored by the International Pancreas & Islet Transplant Association (IPITA) and the European Pancreas & Islet Transplant Association. In July 2019, a symposium at the 17th IPITA World Congress was held to examine the Igls criteria after 2 years in clinical practice, including validation against continuous glucose monitoring (CGM)-derived glucose targets, and to propose future refinements that would allow for comparison of outcomes with artificial pancreas system approaches. Evidence acquisition Utilization of the criteria in various clinical and research settings was illustrated by population as well as individual outcome data of 4 islet and/or pancreas transplant centers. Validation against CGM metrics was conducted in 55 islet transplant recipients followed-up to 10 years from a fifth center. Evidence synthesis The Igls criteria provided meaningful clinical assessment on an individual patient and treatment group level, allowing for comparison both within and between different β-cell replacement modalities. Important limitations include the need to account for changes in insulin requirements and C-peptide levels relative to baseline. In islet transplant recipients, CGM glucose time in range improved with each category of increasing β-cell graft function. Conclusions Future Igls 2.0 criteria should consider absolute rather than relative levels of insulin use and C-peptide as qualifiers with treatment success based on glucose assessment using CGM metrics on par with assessment of glycated hemoglobin and severe hypoglycemia events.

Purpose of Review β cell replacement via whole pancreas or islet transplantation has greatly evolved for the cure of type 1 diabetes. Both these strategies are however still affected by several limitations. Pancreas bioengineering holds the potential to overcome these hurdles aiming to repair and regenerate β cell compartment. In this review, we detail the state-of-the-art and recent progress in the bioengineering field applied to diabetes research. Recent Findings The primary target of pancreatic bioengineering is to manufacture a construct supporting insulin activity in vivo. Scaffold-base technique, 3D bioprinting, macro-devices, insulin-secreting organoids, and pancreas-on-chip represent the most promising technologies for pancreatic bioengineering. Summary There are several factors affecting the clinical application of these technologies, and studies reported so far are encouraging but need to be optimized. Nevertheless pancreas bioengineering is evolving very quickly and its combination with stem cell research developments can only accelerate this trend.

Highlights • Nasogastric tube decompression if the first-step treatment of gastric volvulus, which can be placed blindly or under endoscopic guidance. • Prompt endoscopic or surgical assessment should be conducted when signs of sepsis, perforation, or ischemia are present. • Definitive treatment for secondary volvulus is best achieved with hernia reduction, closing of the anatomical defect, and fundoplication. • Primary volvulus can be treated with gastropexy alone., Introduction Gastric volvulus are rare. Complications can be life threatening, including necrosis and perforation. Assessment of mucosal viability is essential, and urgent surgical intervention is mandatory in case of vascular compromise. Presentation of case An 72-year-old female known for a paraesophageal hiatal hernia was admitted at our emergency department with acute abdominal pain. Blood count demonstrated leukocytosis and increased C-reactive protein. Abdominal computed tomography showed a mesenteroaxial gastric volvulus. Urgent upper endoscopy revealed mucosal ischemia, which prompted immediate laparotomy with partial gastrectomy, cruroplasty, and Dor fundoplication. Postoperative course was uneventful. Discussion Gastric volvulus is initially treated with nasogastric tube decompression, but definitive treatment is achieved surgically. When there is an associated hernia, closing the anatomical defect and fundoplication should be performed. Complication such as necrosis is associated with a high mortality, and requires urgent surgical repair. Conclusion Gastric volvulus can be life-threatening. Urgent endoscopic or surgical assessment should be conducted to assess mucosal viability.

Therapeutically guided multidrug optimization (TGMO) technology, composed of experimental testing and in silico modelling, allowed identification of synergistic and selective low‐dose optimized drug combinations (ODCs) active in multiple colorectal carcinoma models. The mechanisms of action of the ODCs was established using transcriptome sequencing and phosphoproteomic analyses. Our results indicate that simultaneous multitarget inhibition of important deregulated pathways has strong therapeutic potential and translational value between tumor types., The current standard of care for colorectal cancer (CRC) is a combination of chemotherapeutics, often supplemented with targeted biological drugs. An urgent need exists for improved drug efficacy and minimized side effects, especially at late‐stage disease. We employed the phenotypically driven therapeutically guided multidrug optimization (TGMO) technology to identify optimized drug combinations (ODCs) in CRC. We identified low‐dose synergistic and selective ODCs for a panel of six human CRC cell lines also active in heterotypic 3D co‐culture models. Transcriptome sequencing and phosphoproteome analyses showed that the mechanisms of action of these ODCs converged toward MAP kinase signaling and cell cycle inhibition. Two cell‐specific ODCs were translated to in vivo mouse models. The ODCs reduced tumor growth by ~80%, outperforming standard chemotherapy (FOLFOX). No toxicity was observed for the ODCs, while significant side effects were induced in the group treated with FOLFOX therapy. Identified ODCs demonstrated significantly enhanced bioavailability of the individual components. Finally, ODCs were also active in primary cells from CRC patient tumor tissues. Taken together, we show that the TGMO technology efficiently identifies selective and potent low‐dose drug combinations, optimized regardless of tumor mutation status, outperforming conventional chemotherapy.

The success of pancreas islet isolation largely depends on donor characteristics, including extracellular matrix composition of which collagen is the main element. We hypothesized that isolation yields are proportional to collagen digestion percentage, and aimed to determine a threshold that predicts isolation success. The amount of pancreas collagen (I-V) was determined using colorimetry prior to and after the digestion process in 52 human islet isolations. Collagen I-V and VI were also assessed histologically. We identified a collagen digestion threshold of ≥ 60% as an independent factor beyond which an islet preparation has a ninefold increased odds of yielding ≥ 250 000 islet equivalents (IEQ) (P = 0.009) and a sixfold increased odds of being transplanted (P = 0.015). Preparations with ≥ 60% collagen digestion (n = 35) yielded 283 017 ± 164 214 IEQ versus 180 142 ± 85 397 in the < 60% collagen digestion group (n = 17) (P = 0.016); respectively 62.9% versus 29.4% of those were transplanted (P = 0.024). Common donor characteristics, initial collagen content, enzyme blend, and digestion times were not associated with collagen digestion percentage variations. Donor age positively correlated with the amount of collagen VI (P = 0.013). There was no difference in islet graft survival between high and low digestion groups. We determined that a 60% pancreas collagen digestion is the threshold beyond which an islet isolation is likely to be successful and transplanted.

Macrovascular invasion is considered a contraindication to liver transplantation for hepatocellular carcinoma (HCC) due to a high risk of recurrence. The aim of the present multicenter study was to explore the outcome of HCC patients transplanted after a complete radiological regression of the vascular invasion by locoregional therapies and define sub-groups with better outcomes. Medical records of 45 patients were retrospectively reviewed, and imaging was centrally assessed by an expert liver radiologist. In the 30 patients with validated diagnosis of macrovascular invasion, overall survival was 60% at 5 years. Pretransplant alpha-fetoprotein (AFP) value was significantly different between patients with and without recurrence (P = 0.019), and the optimal AFP cutoff was 10ng/ml (area under curve = 0.78). Recurrence rate was 11% in patients with pretransplant AFP < 10ng/ml. The number of viable nodules (P = 0.008), the presence of residual HCC (P = 0.036), and satellite nodules (P = 0.001) on the explant were also significantly different between patients with and without recurrence. Selected HCC patients with radiological signs of vascular invasion could be considered for transplantation, provided that they previously underwent successful treatment of the macrovascular invasion resulting in a pretransplant AFP < 10 ng/ml. Their expected risk of post-transplant HCC recurrence is 11%, and further prospective validation is needed.

Lack of rapid revascularization and inflammatory attacks at the site of transplantation contribute to impaired islet engraftment and suboptimal metabolic control after clinical islet transplantation. In order to overcome these limitations and enhance engraftment and revascularization, we have generated and transplanted pre-vascularized insulin-secreting organoids composed of rat islet cells, human amniotic epithelial cells (hAECs), and human umbilical vein endothelial cells (HUVECs). Our study demonstrates that pre-vascularized islet organoids exhibit enhanced in vitro function compared to native islets, and, most importantly, better engraftment and improved vascularization in vivo in a murine model. This is mainly due to cross-talk between hAECs, HUVECs and islet cells, mediated by the upregulation of genes promoting angiogenesis (vegf-a) and β cell function (glp-1r, pdx1). The possibility of adding a selected source of endothelial cells for the neo-vascularization of insulin-scereting grafts may also allow implementation of β cell replacement therapies in more favourable transplantation sites than the liver.

Evidence suggests that liver graft quality impacts on posttransplant recurrence of hepatocellular carcinoma (HCC). As of today, selection criteria only use variables related to tumor characteristics. Within the Scientific Registry of Transplant Recipients, we identified patients with HCC who underwent liver transplantation between 2004 and 2016 (development cohort, n = 10 887). Based on tumor recurrence rates, we fitted a competing-risk regression incorporating tumor- and donor-related factors, and we developed a prognostic score. Results were validated both internally and externally in the Australia and New Zealand Liver Transplant Registry. Total tumor diameter (subhazard ratio [sub-HR] 1.52 [1.28-1.81]), alpha-feto protein (sub-HR 1.27 [1.23-1.32], recipient male gender (sub-HR 1.43 [1.18-1.74]), elevated donor body mass index (sub-HR 1.26 [1.01-1.58]), and shared graft allocation policy (sub-HR 1.20 [1.01-1.43]) were independently associated with tumor recurrence. We next developed the Darlica score (sub-HR 2.72 [2.41-3.08] P 0.001) that allows identifying risky combinations between a given donor and a given recipient. Results were validated internally (n = 3 629) and externally in the Australia and New Zealand Liver Transplant Registry (n = 370). The current score is based on variables that are readily available at the time of graft offer. It allows identifying hazardous donor-recipient combinations in terms of risk of tumor recurrence and overall survival.

Transplant oncology is a field of growing interest, with increasing number of patients transplanted for cancer [1]. Among such indications, colorectal liver metastasis is under intense scrutiny considering the high number of potential new recipients. The important article by the Oslo group published in the current issue of Transplant International brings more light on their post-transplant fate [2]. Comment on: Dueland S, Smedman TM, Røsok B, Grut H, Syversveen T, Jørgensen LH, Line PD. Treatment of relapse and survival outcomes after liver transplantation in patients with colorectal liver metastases. Transpl Int. 2021 Nov;34(11):2205-2213. doi: 10.1111/tri.13995. PMID: 34792825.

Total pancreatectomy is a procedure primarily performed for chronic pancreatitis refractory to conservative therapy. It may nevertheless be indicated in the event of a malignant tumor, either as a treatment for a surgical complication or as a prevention of anastomotic leakage. If possible, islet auto-transplantation should be combined with total pancreatectomy for benign disease, in order to prevent a severe diabetes. Until recently, malignant disease was considered an absolute contraindication to islet auto-transplantation. A recent series from Milan showed promising oncological results in auto-transplantation for malignant disease, opening up new perspectives for total pancreatectomy for cancer.La pancréatectomie totale est une procédure principalement effectuée pour une pancréatite chronique réfractaire au traitement conservateur. Elle peut néanmoins être indiquée en cas de tumeur maligne, soit comme traitement d’une complication chirurgicale, soit en prévention de fuite anastomotique. Dans la mesure du possible, une autogreffe d’îlots de Langerhans devrait être associée à une pancréatectomie totale pour maladie bénigne, dans le but de prévenir un diabète pancréatoprive. Jusqu’à récemment, une pathologie maligne était considérée comme une contre-indication absolue à une autogreffe d’îlots. Une série récente de Milan a montré des résultats oncologiques prometteurs en cas d’autogreffe pour pathologies malignes, ouvrant de nouvelles perspectives à la pancréatectomie totale pour cancer.

Objective Teaching in the operating room represents the cornerstone of surgical education. Residents need to perform a sufficient number of basic procedures in order to gain independence. However, it is still debated what impact surgical teaching has on outcomes. With this study, we provide recent data of a large national cohort and identify new factors that are associated with increased teaching. Methods We studied common procedures that are essential for surgical training: Laparoscopic Appendectomy (LA), Laparoscopic Cholecystectomy (LC), ostomy closure (OC), laparoscopic (LH) and Open Inguinal Hernia Repair (OH). The national database of the Swiss association for quality management in surgery was screened, and 72072 patients were identified from 2009 to 2019. Teaching was defined as a procedure mainly performed by a surgeon in training under supervision. Results A minority of basic surgical procedures were used for teaching (LA 28.1%, LC 22.3%, OC 21.5%, OH 31.8%, LH 6.3%), even in teaching hospitals of > 200 beds (LA 33.0%, LC 32.9%, OC 27%, OH 51.5%, LH 6.5%). During the study period, there was also generally a trend towards less teaching, exemplified by the two most frequent procedures: LA 35.6 to 26.7% (-25.0%, p = Conclusion The teaching of basic surgical procedures appears safe. Even if associated with longer operating times, it should be promoted as teaching is currently only performed in a minority of procedures (10-33%).

BackgroundHypertension (HT) is associated with adverse outcomes in kidney transplant (KTX) recipients. Blunting of physiological decrease in nighttime compared to daytime blood pressure (non-dipping status) is frequent in this setting. However, weather non-dipping is independently associated with renal function decline in KTX patients is unknown.MethodsWe retrospectively screened KTX outpatients attending for a routine ambulatory blood pressure monitoring (ABPM) (T1) at a single tertiary hospital. Patients had two successive follow-up visits, 1 (T2) and 2 (T3) years later respectively. Routine clinical and laboratory data were collected at each visit. Mixed linear regression models were used with estimated glomerular filtration rate (eGFR) as the dependent variable.ResultsA total of 123 patients were included with a mean follow-up of 2.12 ± 0.45 years after ABPM. Mean age and eGFR at T1 were 56.0 ± 15.1 and 54.9 ± 20.0 mL/min/1.73m2respectively. 61 patients (50.4%) had sustained HT and 81 (65.8%) were non-dippers. In multivariate analysis, systolic dipping status was positively associated with eGFR (p = 0.009) and compared to non-dippers, dippers had a 10.4 mL/min/1.73m2higher eGFR. HT was negatively associated with eGFR (p = 0.003).ConclusionsWe confirm a high prevalence of non-dippers in KTX recipients. We suggest that preserved systolic dipping is associated with improved renal function in this setting independently of potential confounders, including HT and proteinuria. Whether modification of dipping status by chronotherapy would preserve renal function remains to be tested in clinical trials.

This study aimed to assess the global mapping risk of human islet isolation, using a failure mode and effect analysis (FMEA), and highlight the impact of quality assurance procedures on the risk level of criticality. Risks were scored using the risk priority number (RPN) scoring method. The risk level of criticality was made based on RPN and led to risk classification (low to critical). A raw risk analysis and a risk control analysis (with control means and quality assurance performance) were undertaken. The process of human islet isolation was divided into 11 steps, and 230 risks were identified. Analysis of the highest RPN of each of the 11 steps showed that the 4 highest risks were related to the pancreas digestion and islet purification stages. After implementation of reduction measures and controls, critical and severe risks were reduced by 3-fold and by 2-fold, respectively, so that 90% of risks could be considered as low to moderate. FMEA has proven to be a powerful approach for the identification of weaknesses in the islet isolation processes. The results demonstrated the importance of staff qualification and continuous training and supported the contribution of the quality assurance system to risk reduction.

Funder: Fondazione Pisa, Pisa, Italy; Id: http://dx.doi.org/10.13039/100007368, Funder: Tuscany Region, Italy; Id: http://dx.doi.org/10.13039/501100009888, Funder: Pisa University Hospital, Pisa, Italy, Funder: University of Pisa, Pisa, Italy; Id: http://dx.doi.org/10.13039/501100007514, The First World Consensus Conference on Pancreas Transplantation provided 49 jury deliberations regarding the impact of pancreas transplantation on the treatment of diabetic patients, and 110 experts' recommendations for the practice of pancreas transplantation. The main message from this consensus conference is that both simultaneous pancreas-kidney transplantation (SPK) and pancreas transplantation alone can improve long-term patient survival, and all types of pancreas transplantation dramatically improve the quality of life of recipients. Pancreas transplantation may also improve the course of chronic complications of diabetes, depending on their severity. Therefore, the advantages of pancreas transplantation appear to clearly surpass potential disadvantages. Pancreas after kidney transplantation increases the risk of mortality only in the early period after transplantation, but is associated with improved life expectancy thereafter. Additionally, preemptive SPK, when compared to SPK performed in patients undergoing dialysis, appears to be associated with improved outcomes. Time on dialysis has negative prognostic implications in SPK recipients. Increased long-term survival, improvement in the course of diabetic complications, and amelioration of quality of life justify preferential allocation of kidney grafts to SPK recipients. Audience discussions and live voting are available online at the following URL address: http://mediaeventi.unipi.it/category/1st-world-consensus-conference-of-pancreas-transplantation/246.

Background Anemia is a recognized risk factor for perioperative related morbidity and mortality and is frequently reported in liver surgeries with an estimated incidence of 32%. We aim to assess the impact of intravenous iron administration in the immediate postoperative period on anemia and iron status as well as to determine the kinetics of hepcidin after liver surgery. Methods The HepciFer trial, a randomized controlled trial, included 50 patients undergoing liver surgery. In accordance with the randomization process, patients received either ferric carboxymaltose (15 mg/kg, maximum 1 g) or placebo 4 hours after surgery. Results The mean hemoglobin level, 7 days after surgery, did not differ significantly between the intervention and control group (11.1 ± 1.8 g/dL and 10.4 ± 1.6 g/dL, respectively) with a mean difference of +0.7 g/dL ([95% confidence interval, −0.3 to +1.7], P = .173). Within patients receiving intravenous iron supplementation, none presented biological signs of functional iron deficiency. Hepcidin levels remained significantly higher during the observation period in the intervention group. Inflammatory biomarkers, red blood cells transfusion rate and hospital duration of stay were similar between groups. Conclusion Intravenous ferric carboxymaltose administration did not result in a significant increase of hemoglobin levels 7 days after surgery. However, this study suggests that intravenous iron supplementation in the immediate postoperative settings prevents functional iron deficiency. Intravenous iron supplementation overcame the hepcidin-mediated blockade of iron absorption and should be considered as the preferred route of administration in the postoperative period.

Pyogenic-liver abscess is a relatively rare entity in Europe. Due to unspecific clinical and biological findings, the diagnosis can be difficult. Imaging by ultrasound, CT-scan or MRI is important to confirm the diagnosis and to determine further investigations and treatment. According to the characteristics of the abscess, a surgical intervention may be necessary, particularly is the abscess diameter is bigger than 5 cm. This can be done either by surgery or by percutaneous drainage (needle aspiration versus catheter drainage). Obtaining adequate microbiologic cultures is important to identify the responsible pathogens and their resistance profile before starting broad spectrum antibiotics. Antibiotic treatment should be adapted to microbiologic results. The recommended treatment duration is usually between 4 and 6 weeks according to clinical evolution.L’abcès hépatique pyogène (AHP)est un abcès causé par des bactéries. Le diagnostic peut être difficile à poser en raison d’un tableau clinique et biologique aspécifique. L’examen radiologique qu’il soit par échographie, scanner ou IRM a un rôle clé afin d’asseoir le diagnostic. Les caractéristiques morphologiques de l’AHP permettent de déterminer le traitement, qu’il soit conservateur par antibiothérapie seule ou invasif par voie percutanée ou chirurgical. Les examens bactériologiques ont un rôle clé afin d’identifier les bactéries responsables ainsi que leur profil de résistance. Une antibiothérapie empirique doit être introduite dès que les prélèvements bactériologiques ont été effectués, puis être par la suite adapté aux résultats microbiologiques. La durée de traitement est de 4 à 6 semaines selon l’évolution clinique.

Background & Aims: Hyponatremia is an important predictor of early death among cirrhotic patients in the orthotopic liver transplantation (OLT) waiting list. Evidence exists that prioritizing OLT waiting list according to the MELD score combined with plasma sodium concentration might prevent pretransplantation death. However, the evolution of plasma sodium concentrations during the perioperative period of OLT is not well known. We aimed to describe the evolution of perioperative sodium concentration during OLT and its relation to perioperative neurohormonal responses.Methods: Twenty-seven consecutive cirrhotic patients who underwent OLT were prospectively included in the study over a period of 27 months. We studied the evolution of plasma sodium levels, the hemodynamics, the neurohormonal response and other biological markers during the perioperative period of OLT.Results: All patients with a hyponatremia before OLT were in the Child C group. None of the patients had acute or chronic renal impairment. Interestingly, in patients with hyponatremia, plasmatic sodium reached normal levels as soon as the injured livers were removed during surgery and the plasma sodium concentration remained within normal ranges 1 day, 7 days, as well as 6 months after surgery.Conclusions: Further investigation of rapid correction and stabilization of sodium levels after OLT, as observed in our study, would be of interest in order to fully understand the mecanisms involved in cirrhosis related hyponatremia, its prognostic value and clinical implications.

Islet transplantation has experienced significant progress over the past decades, transforming an experimental procedure into an established option for selected patients with type 1 diabetes. Compared to solid organ transplantation, the mandatory multistep conditioning of the pancreas prior to islet transplantation, and the technological infrastructure and know-how it implies, have encouraged the creation of multicenter networks early in the development of islet transplantation programs. The first islet transplantation network created was GRAGIL. It is an example of successful collaboration across national borders, and has contributed and adapted its practices to the successive advances in the field. This chapter describes the rationale for an islet transplantation network, the logistics involved, and the different challenges faced and addressed by the network. These points are illustrated by the several clinical trials completed by GRAGIL and discussed from the network point of view and in perspective with concurrent advances in the field.

Islet transplantation is currently primarily performed as islet transplantation alone (ITA). This is especially the case in North America, less so in the rest of the world, since the turn of the millennium and the publication of the Edmonton protocol. The main indication for ITA is “problematic hypoglycemia,” a term describing patients experiencing repeated episodes of severe hypoglycemia, mostly due to hypoglycemia unawareness. Candidates usually have normal kidney function. The risks and benefits of exposure to long-term immunosuppression should therefore be carefully balanced before selecting patients for ITA, a concern that is not present in uremic patients who are also candidates for a kidney transplant. The different parameters to take into account for selecting patients for ITA are reviewed in this chapter, as well as the tools for assessment at baseline and during posttransplant follow-up. Criteria for directing patients with problematic hypoglycemia toward pancreas or islet transplant alone are also discussed.

Six years after publishing their first results on liver transplantation for colorectal liver metastases (SECA-I) (1), Dueland et al . present a new trial on the same topic gathering 15 transplanted patients (SECA-II). They now use more restricted selection criteria, including at least 1 year between cancer diagnosis and transplantation, a documented partial (>10%) response to chemotherapy, and the absence of extra-hepatic metastasis.

Robotic surgery has emerged as a promising minimally invasive surgical technique, with the ability to perform complex hepatobiliary surgeries and achieve outcomes similar to open surgery, but with the advantages of a minimally invasive approach. Recent advances in computer-assisted image-guided surgery are proposed to overcome some of the associated limitations of robotic surgery by preoperatively planning the surgical strategy with a patient-specific virtual resection plan, which can be directly transferred to the operating room in an augmented reality setup. Using new technologies, we could theoretically improve the preoperative planning, enhance the surgeon’s skill, and simplify complex procedures. Specifically, using an optical tracking system, calibrated on the patient, we used images-overlay navigation for the location of the lesions during robotic liver resections. Based on our experience, we suggest that robotic image guidance can improve the surgeon’s orientation during the operation, increasing the accuracy of tumor resection. The indications for robotic-assisted liver resection will increase in the coming years. This chapter reviews the recent development of robotic hepatic surgery, discussing its advantages and disadvantages in daily practice. The most common surgical procedures are described and, finally, the evolution of robotic surgery, one of the hottest fields in medical technology, is detailed.

The population of liver transplant recipients has increased in Switzerland over the last few years. Morbidity and mortality after liver transplantation are due, in the early post-transplant period, to surgical and infectious complications as well as to rejection, whereas cardiovascular, metabolic, renal and oncologic complications are the most frequent complications in the late post-transplant period. The role of the general practitioner in the long-term follow-up of liver transplant recipients is of the highest importance and can represent the first-line care of these patients as soon as 6 to 12 months post-transplantation, while maintaining a close and regular collaboration with the transplant center. Multidisciplinary and structured follow-up, along with some specific screening tests, is warranted in order to refine patient management in a timely manner and to optimize outcomes.Les patients greffés hépatiques représentent une population croissante en Suisse. La morbidité et la mortalité après cette procédure sont liées

Abdominal surgery is sometimes needed in patients with portal hypertension. The indication may be related to the underlying liver disease, including liver resection for liver cancer and parietal surgery. Surgery may also be performed for another indication, unrelated to the liver disease. Portal hypertension increases both morbidity and mortality after abdominal surgery, and it should be taken into account when planning surgery timing and surgical strategy. This article provides an overview of the main etiologies of portal hypertension, and the post-operative outcomes after liver resection and non-hepatic abdominal surgery, underlining the importance of a multidisciplinary approach.Une chirurgie abdominale est parfois nécessaire chez les patients atteints d’hypertension portale. Son indication peut être en lien avec une complication de la maladie du foie, comme une résection de tumeur hépatique ou une chirurgie pariétale, ou avec une affection non liée à la pathologie hépatique. L’hypertension portale augmente la morbidité et la mortalité de cette chirurgie, et l’indication ainsi que la stratégie doivent être définies avec soin. Cet article décrit les causes d’hypertension portale, les risques associés à sa présence lors d’une résection hépatique ou d’une chirurgie abdominale non hépatique. Enfin, il propose une approche multidisciplinaire, associant les chirurgiens, les hépatologues, les anatomopathologistes et les anesthésistes-réanimateurs.

While either pancreas or pancreatic islet transplantation can restore endogenous insulin secretion in patients with diabetes, no beta-cell replacement strategies are recommended in the literature. For this reason, the aim of this national expert panel statement is to provide information on the different kinds of beta-cell replacement, their benefit-risk ratios and indications for each type of transplantation, according to type of diabetes, its control and association with end-stage renal disease. Allotransplantation requires immunosuppression, a risk that should be weighed against the risks of poor glycaemic control, diabetic lability and severe hypoglycaemia, especially in cases of unawareness. Pancreas transplantation is associated with improvement in diabetic micro- and macro-angiopathy, but has the associated morbidity of major surgery. Islet transplantation is a minimally invasive radiological or mini-surgical procedure involving infusion of purified islets via the hepatic portal vein, but needs to be repeated two or three times to achieve insulin independence and long-term functionality. Simultaneous pancreas-kidney and pancreas after kidney transplantations should be proposed for kidney recipients with type 1 diabetes with no surgical, especially cardiovascular, contraindications. In cases of high surgical risk, islet after or simultaneously with kidney transplantation may be proposed. Pancreas, or more often islet, transplantation alone is appropriate for non-uraemic patients with labile diabetes. Various factors influencing the therapeutic strategy are also detailed in this report.

Background. We report the histopathological results of a novel ‘‘inversed’’ strategy designed to manage patients with colorectal cancer (CRC) who have synchronous liver metastases by using chemotherapy first, liver surgery second, and resection of the primary tumor as a final step. This study was designed to compare the response to chemotherapy in liver metastases, primary tumors, and locoregional lymph nodes. Methods. Twenty-nine patients with stage IV CRC received a combination of oxaliplatin, irinotecan, 5-fluorouracil, and leucovorin (OCFL) for 3–4 months. Histological response to chemotherapy was assessed by using a tumor regression grading (TRG) score based on presence of residual tumor cells and extent of fibrosis. Results. Median age of patients was 56 (range, 37–69) years. Primary tumor location was right colon ( n= 5), left colon ( n= 7), and rectum ( n= 17 patients). TRG scores correlated across disease sites (Spearman correlation coefficients for TRG in the primary tumor and lymph nodes was 0.59 [ P= 0.005]; for the primary tumor and metastases 0.44 [ P= 0.021]; and for lymph nodes and metastases 0.58 [ P= 0.006]). Complete absence or poor tumor response (TRG4/5) was significantly more frequent in primary tumors (35.7%) and locoregional lymph nodes (38%) than in liver metastases (6.9%; McNemar test, P= 0.02). Two patients had a complete pathologic response (pT0N0M0). Conclusions. In patients with stage IV colorectal cancer, liver metastases exhibit a better histological response than primary tumors to OCFL neoadjuvant chemotherapy.

The use of downstaging prior to liver transplantation for hepatocellular carcinoma (HCC) still needs refinement. This study included patients with HCC listed for transplantation according to the Total Tumour Volume (TTV) ≤115 cm3 and alpha fetoprotein (AFP) ≤400 ng/ml criteria, with and without previous downstaging. Overall, 455 patients were listed, and 286 transplanted. Post-transplant follow-up was 38.5 ± 1.7 months. Patients downstaged to TTV115/AFP400 (n = 29) demonstrated similar disease-free survivals (DFS, 74% vs. 80% at 5 years, P = 0.949), but a trend to more recurrences (14% vs. 5.8%, P = 0.10) than those always within TTV115/AFP400 (n = 257). Similarly, patients downstaged to Milan criteria (n = 80) demonstrated similar DFS (76% vs. 86% at 5 years, P = 0.258), but more recurrences (11% vs. 1.7%, P = 0.001) than those always within Milan (n = 177). Among patients downstaged to Milan, those originally beyond TTV115/AFP400 (n = 27) had similar outcomes as those originally beyond Milan, but within TTV115/AFP400 (n = 53). However, the likelihood of being within Milan at transplant was lower for patients with more advanced original HCCs (P < 0.0001). Overall, despite an expected increase in post-transplant HCC recurrence, similar survivals can be achieved with and without downstaging, using the TTV115/AFP400 transplantation criteria, and including patients with advanced original HCCs. Downstaging should continue to be performed.

Allogeneic islet of Langerhans transplantation is a recognized beta-cell replacement therapy for patients affected by type 1 diabetes mellitus. Type 1 diabetes mellitus is a condition associated with an increased risk of adverse outcomes for pregnant women and fetuses We report the case of a 29 year-old woman with type 1 diabetes mellitus, who underwent successful allogeneic islet transplantation with simultaneous kidney transplantation. She achieved durable insulin independence after two islet infusions. Pregnancy was desired and planned 2 years after last islet infusion. Multidisciplinary monitoring of pregnancy was carried out and immunosuppressive regimen was adapted. Euglycemia was maintained throughout pregnancy without the need for exogenous insulin. After an uneventful pregnancy, she delivered on term an otherwise healthy male child with imperforate anus that was immediately surgically corrected. In conclusion, allogeneic islet transplantation is a suitable treatment for women of childbearing age with complicated type 1 diabetes mellitus, allowing physiologic glycemic control during pregnancy with a low risk of graft loss. This target can only be achieved by a tight multidisciplinary follow-up, including immunosuppressive therapy adaptation and adequate diabetes and obstetrical monitoring. This article is protected by copyright. All rights reserved.

The article by Parajuli et al published in this issue of Transplant International is the latest, and perhaps the most convincing in a relatively small body of literature, to suggest that in a situation of simultaneous pancreas-kidney transplantation (SPK), in which both organs are from the same donor, one organ may be undergoing acute rejection independently from the other (1). The organ hierarchy in immunogeneicity and susceptibility to rejection is a long known biological phenomenon, with the liver at one end of the spectrum and the intestine the other. It was originally thought that such a hierarchy between kidney and pancreas was in disfavor of the latter (2). This article is protected by copyright. All rights reserved.

Background The role of intraoperative cholangiogram (IOC) during cholecystectomy is debated. The aim of the present study was to evaluate the feasibility, benefit and risk of performing systematic IOC in patients undergoing cholecystectomy for acute gallstone-related disease. Methods Between July 2013 and January 2015, all patients admitted for an acute gallstone-related condition and undergoing same-hospital-stay cholecystectomy were prospectively followed. IOC was systematically attempted and predictors of IOC failure were analyzed. Results Among the 581 enrolled patients, IOC was deliberately not performed in 3 cases. IOC was successful in 509/578 patients (88.1%). The main predictors of IOC failure were age, body mass index, male gender and associated acute cholecystitis. Thirty-two patients with suspected common bile duct stone on IOC underwent 38 unnecessary negative postoperative common bile duct investigations (32/509, 6.3%). There was one IOC-related adverse outcome (mild pancreatitis, 1/578, 0.2%). Conclusions IOC can be successfully and safely performed in the majority of patients undergoing cholecystectomy for acute gallstone-related disease. Although its positive predictive value is suboptimal and results in a number of unnecessary postoperative common bile duct investigations, IOC accurately rules out common bile duct stones in patients with acute gallstone-related conditions.

Deciding who should receive a liver transplant (LT) depends on both urgency and utility. Most survival scores are validated through discriminative tests, which compare predicted outcomes between patients. Assessing post-transplant survival utility is not discriminate, but should be “calibrated” to be effective. There are currently no such calibrated models. We developed and validated a novel calibrated model to predict individual survival after LT for Primary Sclerosing Cholangitis (PSC). We applied a software tool, PSSP, to adult patients in the Scientific Registry of Transplant Recipients (n = 2769) who received a LT for PSC between 2002 and 2013; this produced a model for predicting individual survival distributions for novel patients. We also developed an appropriate evaluation measure, D-calibration, to validate this model. The learned PSSP model showed an excellent D-calibration (p = 1.0), and passed the single-time calibration test (Hosmer-Lemeshow p-value of over 0.05) at 0.25, 1, 5 and 10 years. In contrast, the model based on traditional Cox regression showed worse calibration on long-term survival and failed at 10 years (Hosmer-Lemeshow p value = 0.027). The calculator and visualizer are available at: http://pssp.srv.ualberta.ca/calculator/liver_transplant_2002. In conclusion we present a new tool that accurately estimates individual post liver transplantation survival.

Clustering, an unsupervised learning method, can be very useful in detecting hidden patterns in complex and/or high-dimensional data. Persistent homology, a recently developed branch of computational topology, studies the evolution of topological features under a varying filtration parameter. At a fixed filtration parameter value, one can find different topological features in a dataset, such as connected components (zero-dimensional topological features), loops (one-dimensional topological features), and more generally, k-dimensional holes (k-dimensional topological features). In the classical sense, clusters correspond to zero-dimensional topological features. We explore whether higher dimensional homology can contribute to detecting hidden patterns in data. We observe that some loops formed in survival data seem to be able to detect outliers that other clustering techniques do not detect. We analyze patterns of patients in terms of their covariates and survival time, and determine the most important predictor variables in predicting survival times of liver transplant patients by applying a random survival forest.