The Importance of Multiorgan Procurement in the Improvement of Residents' Open Surgical Skills.

INTRODUCTION: The multiorgan procurement (MOP) represents a chance for the general surgery resident to learn the fundamental steps of open abdominal surgery. The objective of this study was to evaluate the impact of MOP on the residents' open surgical skills. METHODS: Residents' surgical skills were assessed during a 6-month transplant rotation (October 2020-March 2021) using a modified Objective Structured Assessment of Technical Skills with the global rating scale. The surgeries were self-assessed by residents and tutors based on 9 specific steps (SS) and 4 general skills (GS). Each item was rated from 1 (poor) to 5 (excellent) with a maximum score of 45 points for SS and 20 for GS. A crossed-effects linear regression analysis was performed both to evaluate any associations between GS/SS scores and some prespecified covariates, and to study differences in the assessments performed by residents and tutors. RESULTS: Residents actively participated in a total of 59 procurements. In general, there were no significant differences in SS/GS mean scorings between residents (n = 15) and tutors (n = 5). There was a significantly positive association between mean GS/SS scorings and the number of donor surgeries performed (at least 5). Comparing the evaluations of the tutors with the residents, this significance was retained only when scorings were assigned by the tutors. CONCLUSIONS: MOP was shown to improve basic open surgical skills among residents. Awareness of the utility of a clinical rotation in transplant surgery should be raised also on an institutional level.

The role of cold ischemia time and hypothermic perfusion in predicting early hepatocellular carcinoma recurrences after liver transplantation.

AIM: The aim of the study was to identify predictors of early tumor recurrence in patients with hepatocellular carcinoma (HCC) after liver transplantation (LT). METHODS: Retrospective cohort study in 237 consecutive liver recipients with HCC between 2016 and 2021. Multivariate logistic analysis was performed to identify predictors of early HCC recurrences. The impact of hypothermic-oxygenated perfusion (HOPE) on outcome was analyzed after propensity score weighting. RESULTS: Early recurrences were observed in 15 cases. Microvascular invasion (OR 3.737, 95% CI 1.246-11.206, p = 0.019) and cold ischemia time (OR 1.155, 95% CI 1.001-1.333, p = 0.049) were independently associated with a lower risk of HCC recurrences. After balancing for relevant variables, patients in the HOPE group had lower rates of tumor recurrence (weighted OR 0.126, 95% CI 0.016-0.989, p = 0.049) and higher recurrence free survival (weighted HR 0.132, 95% CI 0.017-0.999, p = 0.050). CONCLUSION: Reducing cold ischemia time and graft perfusion with HOPE can lead to lower rates of early HCC recurrences and higher recurrence-free survival.

Genetic determinants of type 1 diabetes in individuals with weak evidence of islet autoimmunity at disease onset.

AIMS/HYPOTHESIS: Islet autoantibodies (AAbs) are detected in >90% of individuals with clinically suspected type 1 diabetes at disease onset. A single AAb, sometimes at low titre, is often detected in some individuals, making their diagnosis uncertain. Type 1 diabetes genetic risk scores (GRS) are a useful tool for discriminating polygenic autoimmune type 1 diabetes from other types of diabetes, particularly the monogenic forms, but testing is not routinely performed in the clinic. Here, we used a type 1 diabetes GRS to screen for monogenic diabetes in individuals with weak evidence of autoimmunity, i.e. with a single AAb at disease onset. METHODS: In a pilot study, we genetically screened 142 individuals with suspected type 1 diabetes, 42 of whom were AAb-negative, 27 of whom had a single AAb (single AAb-positive) and 73 of whom had multiple AAbs (multiple AAb-positive) at disease onset. Next-generation sequencing (NGS) was performed in 41 AAb-negative participants, 26 single AAb-positive participants and 60 multiple AAb-positive participants using an analysis pipeline of more than 200 diabetes-associated genes. RESULTS: The type 1 diabetes GRS was significantly lower in AAb-negative individuals than in those with a single and multiple AAbs. Pathogenetic class 4/5 variants in MODY or monogenic diabetes genes were identified in 15/41 (36.6%) AAb-negative individuals, while class 3 variants of unknown significance were identified in 17/41 (41.5%). Residual C-peptide levels at diagnosis were higher in individuals with mutations compared to those without pathogenetic variants. Class 3 variants of unknown significance were found in 11/26 (42.3%) single AAb-positive individuals, and pathogenetic class 4/5 variants were present in 2/26 (7.7%) single AAb-positive individuals. No pathogenetic class 4/5 variants were identified in multiple AAb-positive individuals, but class 3 variants of unknown significance were identified in 19/60 (31.7%) patients. Several patients across the three groups had more than one class 3 variant. CONCLUSIONS/INTERPRETATION: These findings provide insights into the genetic makeup of patients who show weak evidence of autoimmunity at disease onset. Absence of islet AAbs or the presence of a single AAb together with a low type 1 diabetes GRS may be indicative of a monogenic form of diabetes, and use of NGS may improve the accuracy of diagnosis.

Follicular helper T cell signature of replicative exhaustion, apoptosis, and senescence in common variable immunodeficiency.

Common variable immunodeficiency (CVID) is the most frequent primary antibody deficiency whereby follicular helper T (Tfh) cells fail to establish productive responses with B cells in germinal centers. Here, we analyzed the frequency, phenotype, transcriptome, and function of circulating Tfh (cTfh) cells in CVID patients displaying autoimmunity as an additional phenotype. A group of patients showed a high frequency of cTfh1 cells and a prominent expression of PD-1 and ICOS as well as a cTfh mRNA signature consistent with highly activated, but exhausted, senescent, and apoptotic cells. Plasmatic CXCL13 levels were elevated in this group and positively correlated with cTfh1 cell frequency and PD-1 levels. Monoallelic variants in RTEL1, a telomere length- and DNA repair-related gene, were identified in four patients belonging to this group. Their blood lymphocytes showed shortened telomeres, while their cTfh were more prone to apoptosis. These data point toward a novel pathogenetic mechanism in CVID, whereby alterations in DNA repair and telomere elongation might predispose to antibody deficiency. A Th1, highly activated but exhausted and apoptotic cTfh phenotype was associated with this form of CVID.

Can repeated surgical resection offer a chance of cure for recurrent cholangiocarcinoma?

INTRODUCTION: The incidence of cholangiocarinoma (CCA), as well as the related mortality rate, has progressively increased over the last decades. Nevertheless improvement in patient management, diagnosis and therapies, recurrence rate remains high (50-70%) with a low 5-year survival (7-20%). Palliative chemotherapy and best supportive care are the treatment of choice in case of recurrence. In recent years, some reports have been published on repeated resection suggesting a survival benefit. The aim of this study was to evaluate the long-term outcome of all repeated resections for recurrent CCA in our institution. MATERIALS AND METHODS: We performed a retrospective analysis of all data recorded in our prospective maintained database of all patients who underwent repeated resection for recurrence of any type of CCA (intrahepatic, perihilar, distal, and gallbladder) with curative intent in our institution. RESULTS: Between 1997 and 2017, twenty-six patients underwent repeated surgical resection for recurrent CCA. Median time to first recurrence was 20 months. Site of recurrence was liver in 18 patients (70%), lymph nodes in 6 (23%), and lungs in 2 (7%). Twenty-five patients (96%) underwent upfront surgical resection of the recurrence, while one received preoperative chemotherapy. Median overall and disease-free survival from repeated surgical resection was 21 and 18 months with a 1-, 3-, and 5-year survival of 87, 41, 29% and 75%, 27%, and 17% respectively. Five patients (21%) did not experience recurrence after repeated surgical resection after a median follow-up of 73 months. CONCLUSIONS: Repeated surgical resection of recurrent CCAs is feasible with good postoperative results and can lead to an increase in survival.

Hypothermic oxygenated perfusion in extended criteria donor liver transplantation-A randomized clinical trial.

Hypothermic Oxygenated Perfusion (HOPE) of the liver can reduce the incidence of early allograft dysfunction (EAD) and failure in extended criteria donors (ECD) grafts, although data from prospective studies are very limited. In this monocentric, open-label study, from December 2018 to January 2021, 110 patients undergoing transplantation of an ECD liver graft were randomized to receive a liver after HOPE or after static cold storage (SCS) alone. The primary endpoint was the incidence of EAD. The secondary endpoints included graft and patient survival, the EASE risk score, and the rate of graft or other graft-related complications. Patients in the HOPE group had a significantly lower rate of EAD (13% vs. 35%, p = .007) and were more frequently allocated to the intermediate or higher risk group according to the EASE score (2% vs. 11%, p = .05). The survival analysis confirmed that patients in the HOPE group were associated with higher graft survival one year after LT (p = .03, log-rank test). In addition, patients in the SCS group had a higher re-admission and overall complication rate at six months, in particular cardio-vascular adverse events (p = .04 and p = .03, respectively). HOPE of ECD grafts compared to the traditional SCS preservation method is associated with lower dysfunction rates and better graft survival.

Health care organization and use of technological devices in people with diabetes in Italy: Results from a survey of the Working Group on Diabetes and Technology.

BACKGROUND AND AIM: The use of technology offers recognized benefits to persons with diabetes. The aim of this study was to evaluate the organization of healthcare facilities, the composition of the diabetes team, and the use of Continuous Subcutaneous Insulin Infusion (CSII) and Continuous Glucose Monitoring (CGM) in Italy. METHODS AND RESULTS: Diabetes care centers were asked to complete a web survey based on information collected in 2018. Sixty-one pediatric and 243 adult centers participated in the survey, accounting for 507,386 patients, mostly with type 2 diabetes (86.4%). Fifty-three percent of pediatric centers and 11% of adult centers reported a team composed of diabetologists, nurses, and psychologists. Overall, 13,204 patients (2.6%) were using CSII (95% with type 1 diabetes), and 28,936 (5.7%), were using CGM (74% with type 1 diabetes). When stratifying for the type of diabetes, 24% and 40.8% of patients with type 1 were using CSII and CGM, respectively, whereas low use of technology was reported for patients with type 2 and women with gestational diabetes. The percentage of adult and pediatric patients with type 1 diabetes on CSII and CGM was respectively 21% and 32%, and 35% and 57%. CONCLUSIONS: The spread of CGM and CSII increased in Italy between 2013 and 2018. However, the percentage of users is still lower than what is expected based on clinical indications for use of technology. The inadequate number of professionals in the diabetes care team and insufficient economic resources are relevant barriers to disseminating technology for diabetes management.

Antibody response to multiple antigens of SARS-CoV-2 in patients with diabetes: an observational cohort study.

AIMS/HYPOTHESIS: The aim of the study was to characterise the humoral response against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in patients with diabetes. Demonstrating the ability to mount an appropriate antibody response in the presence of hyperglycaemia is relevant for the comprehension of mechanisms related to the observed worse clinical outcome of coronavirus disease 2019 (COVID-19) pneumonia in patients with diabetes and for the development of any future vaccination campaign to prevent SARS-CoV-2 infection. METHODS: Using a highly specific and sensitive measurement of antibodies by fluid-phase luciferase immunoprecipitation assays, we characterised the IgG, IgM and IgA response against multiple antigens of SARS-CoV-2 in a cohort of 509 patients with documented diagnosis of COVID-19, prospectively followed at our institution. We analysed clinical outcomes and antibody titres according to the presence of hyperglycaemia, i.e., either diagnosed or undiagnosed diabetes, at the time of, or during, hospitalisation. RESULTS: Among patients with confirmed COVID-19, 139 (27.3%) had diabetes: 90 (17.7%) had diabetes diagnosed prior to the hospital admission (comorbid diabetes) while 49 (9.6%) had diabetes diagnosed at the time of admission (newly diagnosed). Diabetes was associated with increased levels of inflammatory biomarkers and hypercoagulopathy, as well as leucocytosis and neutrophilia. Diabetes was independently associated with risk of death (HR 2.32 [95% CI 1.44, 3.75], p = 0.001), even after adjustment for age, sex and other relevant comorbidities. Moreover, a strong association between higher glucose levels and risk of death was documented irrespective of diabetes diagnosis (HR 1.14 × 1.1 mmol/l [95% CI 1.08, 1.21], p < 0.001). The humoral response against SARS-CoV-2 in patients with diabetes was present and superimposable, as for timing and antibody titres, to that of non-diabetic patients, with marginal differences, and was not influenced by glucose levels. Of the measured antibody responses, positivity for IgG against the SARS-CoV-2 spike receptor-binding domain (RBD) was predictive of survival rate, both in the presence or absence of diabetes. CONCLUSIONS/INTERPRETATION: The observed increased severity and mortality risk of COVID-19 pneumonia in patients with hyperglycaemia was not the result of an impaired humoral response against SARS-CoV-2. RBD IgG positivity was associated with a remarkable protective effect, allowing for a cautious optimism about the efficacy of future vaccines against SARs-COV-2 in people with diabetes. Graphical abstract.

Reduced PD-1 expression on circulating follicular and conventional FOXP3+ Treg cells in children with new onset type 1 diabetes and autoantibody-positive at-risk children.

Autoantibodies (AAbs) are a hallmark of Type 1 diabetes (T1D). Alterations in the frequency and phenotype of follicular helper (Tfh) T cells have been previously documented in patients with type 1 diabetes (T1D), but the contribution of follicular regulatory T (Treg) cells, which are responsible for suppressing AAb development, is less clear. Here, we investigated the frequency and activation status of follicular (CXCR5+) and conventional (CXCR5-) Treg cells in the blood of children with new-onset T1D, and children with risk for developing T1D (AAb-positive) and compared them to AAb-negative controls. Blood follicular and conventional Treg cells were higher in frequency in children with new onset T1D, but expressed reduced amounts of PD-1 as compared to AAb-negative children. Interestingly, the proportion of circulating FOXP3+ Tregs expressing PD-1 was also reduced in AAb-positive at-risk children as compared to AAb-negative controls, suggesting its potential use as a biomarker of disease progression. Follicular Treg cells were reduced in frequency in the spleens of prediabetic NOD mice as they became older and turned diabetic. Interestingly, PD-1 expression declined also on circulating follicular and conventional Treg cells in prediabetic NOD mice as they aged. Together, these findings show that the frequency of circulating follicular and conventional Treg cells and their levels of PD-1 change with disease progression in children at-risk for developing T1D and in NOD mice.

Delivery of hepato-pancreato-biliary surgery during the COVID-19 pandemic: an European-African Hepato-Pancreato-Biliary Association (E-AHPBA) cross-sectional survey.

BACKGROUND: The extent of the COVID-19 pandemic and the resulting response has varied globally. The European and African Hepato-Pancreato-Biliary Association (E-AHPBA), the premier representative body for practicing HPB surgeons in Europe and Africa, conducted this survey to assess the impact of COVID-19 on HPB surgery. METHODS: An online survey was disseminated to all E-AHPBA members to assess the effects of the pandemic on unit capacity, management of HPB cancers, use of COVID-19 screening and other aspects of service delivery. RESULTS: Overall, 145 (25%) members responded. Most units, particularly in COVID-high countries (>100,000 cases) reported insufficient critical care capacity and reduced HPB operating sessions compared to COVID-low countries. Delayed access to cancer surgery necessitated alternatives including increased neoadjuvant chemotherapy for pancreatic cancer and colorectal liver metastases, and locoregional treatments for hepatocellular carcinoma. Other aspects of service delivery including COVID-19 screening and personal protective equipment varied between units and countries. CONCLUSION: This study demonstrates that the COVID-19 pandemic has had a profound adverse impact on the delivery of HPB cancer care across the continents of Europe and Africa. The findings illustrate the need for safe resumption of cancer surgery in a "new" normal world with screening of patients and staff for COVID-19.

Evaluation of a micro-spectrometer for the real-time assessment of liver graft with mild-to-moderate macrosteatosis: A proof of concept study.

BACKGROUND & AIMS: Liver macrosteatosis (MS) is a major predictor of graft dysfunction after transplantation. However, frozen section techniques to quantify steatosis are often unavailable in the context of procurements, and the findings of preoperative imaging techniques correlate poorly with those of permanent sections, so that the surgeon is ultimately responsible for the decision. Our aim was to assess the accuracy of a non-invasive pocket-sized micro-spectrometer (PSM) for the real-time estimation of MS. METHODS: We prospectively evaluated a commercial PSM by scanning the liver capsule. A double pathological quantification of MS was performed on permanent sections. Initial calibration (training cohort) was performed on 35 livers (MS ≤60%) and an algorithm was created to correlate the estimated (PSM) and known (pathological) MS values. A second assessment (validation cohort) was then performed on 154 grafts. RESULTS: Our algorithm achieved a coefficient of determination R2 = 0.81. Its validation on the second cohort demonstrated a Lin's concordance coefficient of 0.78. Accuracy reached 0.91%, with reproducibility of 86.3%. The sensitivity, specificity, positive and negative predictive values for MS ≥30% were 66.7%, 100%, 100% and 98%, respectively. The PSM could predict the absence (<30%)/presence (≥30%) of MS with a kappa coefficient of 0.79. Neither graft weight nor height, donor body mass index nor the CT-scan liver-to-spleen attenuation ratio could accurately predict MS. CONCLUSION: We demonstrated that a PSM can reliably and reproducibly assess mild-to-moderate MS. Its low cost and the immediacy of results may offer considerable added-value decision support for surgeons. This tool could avoid the detrimental and prolonged ischaemia caused by the pathological examination of (potentially) marginal grafts. This device now needs to be assessed in the context of a large-scale multicentre study. LAY SUMMARY: Macro-vacuolar liver steatosis is a major prognostic factor for outcomes after liver transplantation. However, it is often difficult for logistical reasons to get this estimation during procurement. Therefore, we developed an algorithm for a commercial, portable and affordable spectrometer to accurately estimate this content in a real-time fashion. This device could be of great interest for clinical decision-making to accept or discard a potential human liver graft.

Perihilar Glissonian Approach for Anatomical Parenchymal Sparing Liver Resections: Technical Aspects: The Taping Game.

OBJECTIVE: To present technical details for central hepatectomy and right anterior and posterior sectionectomies using perihilar Glissonian approach for anatomical delineation and selective inflow occlusion. BACKGROUND: Central tumors and those deeply located in the right liver may require extensive resections because of their proximity to major vascular structures. In such cases, anatomical more limited resections such as central hepatectomy or sectionectomies may provide an alternative to extensive surgery by assuring both parenchymal sparing and suitable oncologic resection. METHODS: We present the global concept for performing a perihilar Glissonian approach and its application to each individual anatomical procedure. This includes detailed descriptions, illustrations, and videos demonstrating the technique. RESULTS: This technique was applied since 1991 for anatomical parenchymal resections including central hepatectomy (resection of segments 4, 5, and 8), right anterior sectionectomy (resection of segments 5 and 8), and right posterior sectionectomy (resection of segments 6 and 7). The feasibility rate of the Glissonian approach was 88%. CONCLUSIONS: Perihilar Glissonian approach is a safe and reproducible technique that enables anatomical parenchymal preserving liver resections for selected central and right-sided deeply located tumors.

Open Liver Resection, Laparoscopic Liver Resection, and Percutaneous Thermal Ablation for Patients with Solitary Small Hepatocellular Carcinoma (≤30 mm): Review of the Literature and Proposal for a Therapeutic Strategy.

BACKGROUND: Patients with a single hepatocellular carcinoma (HCC) ≤3 cm and preserved liver function have the highest likelihood to be cured if treated. The most adequate treatment methods are yet a matter that is debated. METHODS: We reviewed the literature about open anatomic resection (AR), laparoscopic liver resection (LLR), and percutaneous thermal ablation (PTA). RESULTS: PTA is effective as resection for HCC < 2 cm, when they are neither subcapsular nor perivascular. PTA in HCC of 2-3 cm is under evaluation. AR with the removal of the tumor-bearing portal territory is recommended for HCC > 2 cm, except for subcapsular ones. In comparison with open surgery, LRR has better short-term outcomes and non-inferior long-term outcomes. LLR is standardized for superficial limited resections and for left-sided AR. CONCLUSIONS: According to the available evidences, the following therapeutic proposal can be advanced. Laparoscopic limited resection is the standard for any subcapsular HCC. PTA is the first-line treatment for deep-located HCC < 2 cm, except for those in contact with Glissonean pedicles. Laparoscopic AR is the standard for deep-located HCC of 2-3 cm of the left liver, while open AR is the standard for deep-located HCC of 2-3 cm in the right liver. HCC in contact with Glissonean pedicles should be scheduled for resection (open or laparoscopic) independent of their size. Liver transplantation is reserved to otherwise untreatable patients or as a salvage procedure at recurrence.

Totally intra-corporeal Pringle maneuver during laparoscopic liver resection.

INTRODUCTION: Laparoscopic resection has gained a significant place in liver surgery. As in open liver resection, bleeding control during hepatic transection remains a major issue and it represents the main reason for conversion to laparotomy. Pringle maneuver (PM) remains the standard inflow occlusion technique and a specific step-by-step description of totally intracorporeal laparoscopic PM is described. METHODS: The technique includes placement of a tape around the hepatoduodenal which is then passed through a plastic drain. This creates a tourniquet that is locked with a heavy duty clip to allow intermittent use. RESULTS: This technique has been used in over 400 cases over the past 15 years and has proved safe and efficient with no specific complications encountered. It has been used in in 97 of 170 cases (57%) in the past 4 years and its feasibility has been 97%. Its intracorporeal position does not require an additional trocar and does not interfere with the surgeons' view and operating technique. Cycles of clamping and unclamping can be performed in few seconds including in the emergency setting. CONCLUSIONS: Totally laparoscopic PM is a simple, reproducible and inexpensive method of inflow occlusion during laparoscopic liver resection.

Yttrium-90 Radioembolization for Hepatocellular Carcinoma Prior to Liver Transplantation.

BACKGROUND: Liver transplantation (LT) is a well-established procedure for hepatocellular carcinoma (HCC) within the Milan criteria. Yttrium-90 microspheres radioembolization (Y90-RE) has shown to be an effective and safe treatment of primary liver tumors. We retrospectively evaluate the efficacy of the Y90-RE in patients with HCC prior to LT. METHODS: From January 2002 to December 2015, 365 patients were transplanted at the San Camillo Hospital Center. One hundred forty-three patients were transplanted for HCC, and in 22 cases the patients were treated with Y90-RE before LT. RESULTS: Three patients were treated with Y90-RE within the Milan criteria, and 19 patients were out of criteria before Y90-RE. Four patients had an increasing MELD score between Y90-RE and LT. On the other hand, alpha-fetoprotein decreases after Y90-RE treatment in all cases. No patient death was observed in Y90-RE procedure or at LT. In 78.9 % of cases, a successful downstaging was observed, and in 100 % of cases bridging was achieved. From Y90-RE treatment overall survival was 43.9 months. From LT, overall mean survival was 30.2 months with a free survival of 29.6 months. The overall survival after LT analysis between the patients treated with Y90-RE and patients without was not significant (p = 0.113). Free survival analysis was not significant (p = 0.897) between the two populations. CONCLUSIONS: We successfully performed LT in patients after Y90-RE treatment both as bridging and downstaging for HCC and obtained a similar overall and free survival of LT for HCC within Milan criteria. Y90-RE becomes a real option to provide curative therapy for patients who traditionally are not considered eligible for surgery.

Defining Benchmarks for Major Liver Surgery: A multicenter Analysis of 5202 Living Liver Donors.

OBJECTIVE: To measure and define the best achievable outcome after major hepatectomy. BACKGROUND: No reference values are available on outcomes after major hepatectomies. Analysis in living liver donors, with safety as the highest priority, offers the opportunity to define outcome benchmarks as the best possible results. METHODS: Outcome analyses of 5202 hemi-hepatectomies from living donors (LDs) from 12 high-volume centers worldwide were performed for a 10-year period. Endpoints, calculated at discharge, 3 and 6 months postoperatively, included postoperative morbidity measured by the Clavien-Dindo classification, the Comprehensive Complication Index (CCI), and liver failure according to different definitions. Benchmark values were defined as the 75th percentile of median morbidity values to represent the best achievable results at 3 month postoperatively. RESULTS: Patients were young (34 ± [9] years), predominantly male (65%) and healthy. Surgery lasted 7 ± [2] hours; 2% needed blood transfusions. Mean hospital stay was 11.7± [5] days. 12% of patients developed at least 1 complication, of which 3.8% were major events (≥grade III, including 1 death), mostly related to biliary/bleeding events, and were twice higher after right hepatectomy. The incidence of postoperative liver failure was low. Within 3-month follow-up, benchmark values for overall complication were ≤31 %, for minor/major complications ≤23% and ≤9%, respectively, and a CCI ≤33 in LDs with complications. Centers having performed ≥100 hepatectomies had significantly lower rates for overall (10.2% vs 35.9%, P < 0.001) and major (3% vs 12.1%, P < 0.001) complications and overall CCI (2.1 vs 8.5, P < 0.001). CONCLUSIONS: The thorough outcome analysis of healthy LDs may serve as a reference for evaluating surgical performance in patients undergoing major liver resection across centers and different patient populations. Further benchmark studies are needed to develop risk-adjusted comparisons of surgical outcomes.

Repeat liver retransplantation: rationale and outcomes.

BACKGROUND: Liver retransplantation remains the only option for recurrent graft failure. The aim of our study is to identify predictive factors involved in patients and graft survival for patients undergoing repeat retransplantation (RRT). METHODOLOGY: From January 1985 to December 2012, 2940 liver transplantations were performed in 2477 patients at Paul Brousse Hospital, Villejuif, France. All patients who underwent third, fourth, and fifth transplantation were included in the study and retrospectively analyzed. RESULTS: In the univariate analysis, the factors that were associated with 90-d patient post-operative survival were pre-operative vasopressors support, pre-operative extra hepatic sepsis, primary non-function (PNF) as indication of RRT, recipient's model of end stage liver disease (MELD), urgent RRT, creatinine value at RRT, and prothrombin ratio. The multivariate logistic regression confirmed the role of systemic septic status (OR = 12.8, p = 0.01) and vasopressor drug support (OR = 4.7, p = 0.05) as predictors of post-operative mortality. In the univariate analysis, the factors that were associated with patient 10 yr long-term survival (were vasopressor support, systemic septic patient, PNF as indication of RRT, RRT occurred between 1985 and 1999, recipient's MELD, creatinine value at RRT, and prothrombin ratio. The multivariate logistic regression confirmed the role of systemic septic patient (OR = 6.4, p = 0.03) and the RRT between 1985 and 1999 (OR = 3.6, p = 0.05) as predictors of long-term mortality. CONCLUSION: RRT represent a valid alternative in selected patients. Selection should be oriented on patients needing third transplant without extra hepatic sepsis and vasoactive drug support at moment of RRT. If necessary, fourth and fifth RRT could be performed with a decision made on case-by-case basis, despite a high post-operative mortality.

Laparoscopic Pancreaticoduodenectomy: Right Posterior Superior Mesenteric Artery "First" Approach.

Pancreaticoduodenectomy (PD) is considered one of the most challenging abdominal operations for several reasons, including the anatomy, which is surrounded by vital vascular structures and also because of the serious complications that are possible in the postoperative period. Nowadays, thanks to the development of minimally invasive surgery and improvement of patients' selection, laparoscopic pancreatic resections have been proven to be technically feasible and safe especially in the case of left pancreatectomies. More recently, many series of laparoscopic PD for adenocarcinoma have been published demonstrating the feasibility of this technique. In pancreatic cancer, the advantage of superior mesenteric artery "first approach" is already known to achieve an oncological resection. The purpose of this video is to describe the different technical aspects of the laparoscopic superior mesenteric artery first approach in the right posterior fashion.

Perioperative outcomes of laparoscopic and robot-assisted major hepatectomies: an Italian multi-institutional comparative study.

BACKGROUND: Laparoscopic major hepatectomy (LMH), although safely feasible in experienced hands and in selected patients, is a formidable challenge because of the technical demands of controlling hemorrhage, sealing bile ducts, avoiding gas embolism, and maintaining oncologic surgical principles. The enhanced surgical dexterity offered by robotic assistance could improve feasibility and/or safety of minimally invasive major hepatectomy. The aim of this study was to compare perioperative outcomes of LMH and robotic-assisted major hepatectomy (RMH). METHODS: Pooled data from four Italian hepatobiliary centers were analyzed retrospectively. Demographic data, operative, and postoperative outcomes were collected from prospectively maintained databases and compared. RESULTS: Between January 2009 and December 2012, 25 patients underwent LMH and 25 RMH. The two groups were comparable for all baseline characteristics including type of resection and underlying pathology. Conversion to open surgery was required in one patient in each group (4%). No difference was noted in operative time, estimated blood, and need for allogenic blood transfusions. Intermittent pedicle occlusion was required only in LMH (32% vs. 0; p = 0.004). Length of hospital stay, including time spent in intensive care unit, was similar between the two groups, but patients undergoing LMH showed quicker recovery of bowel activity, with shorter time to first flatus (1 vs. 3 days; p = 0.023) and earlier tolerance to oral liquid diet (1 vs. 2 days; p = 0.001). No difference was noted in complication rate, 90-day mortality, and readmission rate. CONCLUSIONS: This retrospective multi-institution study confirms that selected patients can safely undergo minimally invasive major hepatectomy, either LMH or RMH. The fact that intermittent pedicle occlusion could be avoided in RMH suggests improved surgical ability to deal with bleeding during liver transection, but further studies are needed before any final conclusion can be drawn.

The ALPPS procedure: a surgical option for hepatocellular carcinoma with major vascular invasion.

BACKGROUND: Hepatocellular carcinoma (HCC) tends to have a particular invasiveness toward the portal vein (PV) branches and hepatic veins. This situation can hamper major surgical resection with a risk of postoperative liver failure due to the small future liver remnant (FLR) in cirrhotic livers. These patients are then usually directed to palliative treatments with poor results. The associating liver partition and PV ligation (PVL) in staged hepatectomy (ALPPS) strategy is one of the main surgical innovations in recent years in the field of liver surgical oncology. The ALPPS approach could allow surgical resection in patients with HCC and associated major vascular invasion. METHODS: Among 1,143 liver resection performed in our center, the ALPPS approach was employed in order to induce rapid hypertrophy of the left FLR in patients with HCC and associated major vascular invasion. This strategy consists of combining the in situ splitting of the liver along the main portal scissura or on the right side of the falciform ligament and PVL in a strategy of staged hepatectomy. RESULTS: In our experience the ALPPS approach allowed us to achieve a sufficient FLR in two cases of HCC with major vascular invasion, in which the classic two-stage strategy could not be applied. In both cases the patients could undergo major hepatectomies without mortality. CONCLUSIONS: This novel strategy could expand the number of patients undergoing major liver resections that were previously considered non-resectable because of the risk of liver decompensation for an insufficient FLR.