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BACKGROUND: Minimally invasive surgery has gained momentum for left pancreatic resections. However, debate remains about whether it has any advantage over open surgery for distal pancreatectomy for pancreatic neuroendocrine tumors. METHODS: This retrospective review examined pancreatectomies performed for resectable pancreatic neuroendocrine tumors at 21 centers in France between January 2014 and December 2018. Short and long-term outcomes were compared before and after propensity score matching based on tumor size, sex, age, body mass index, center, and method of pancreatic transection. RESULTS: During the period study, 274 patients underwent left pancreatic resection for pancreatic neuroendocrine tumors [109 underwent distal splenopancreatectomy, and 165 underwent spleen-preserving distal pancreatectomy [(splenic vessel preservation (n = 97; 58.7%)/splenic vessel resection (n = 68; 41.3%)]. Before propensity score matching, minimally invasive surgery was associated with a lower rate of major morbidity (P = .004), lower rate of postoperative delayed gastric emptying (P = .04), and higher rate of "textbook" outcomes (P = .04). After propensity score matching, there were 2 groups of 54 patients (n = 30 distal splenopancreatectomy; n = 78 spleen-preserving distal pancreatectomy). Minimally invasive surgery was associated with less blood loss (P = .05), decreased rate of major morbidity (6% vs. 24%; P = .02), less delayed gastric emptying (P = .05) despite similar rates of postoperative fistula, hemorrhage, and reoperation (P > .05). The 5-year overall survival (79% vs. 75%; P = .74) and recurrence-free survival (10% vs 17%; P = .39) were similar. CONCLUSION: Minimally invasive surgery for left pancreatic resection can be safely proposed for patients with resectable left pancreatic neuroendocrine tumors. Minimally invasive surgery decreases the rate of major complications while providing comparable long-term oncologic outcomes.
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Procedimentos Cirúrgicos Minimamente Invasivos , Tumores Neuroendócrinos , Pancreatectomia , Neoplasias Pancreáticas , Pontuação de Propensão , Humanos , Pancreatectomia/métodos , Pancreatectomia/efeitos adversos , Neoplasias Pancreáticas/cirurgia , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/mortalidade , Feminino , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , França/epidemiologia , Tumores Neuroendócrinos/cirurgia , Tumores Neuroendócrinos/patologia , Tumores Neuroendócrinos/mortalidade , Idoso , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Resultado do Tratamento , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Esplenectomia/métodos , AdultoRESUMO
BACKGROUND: The impact of cirrhosis on the postoperative outcomes of distal pancreatectomy is yet to be reported. We aimed to evaluate the outcomes of distal pancreatectomy in patients with cirrhosis. METHODS: We conducted a retrospective, multicentric study patients with cirrhosis who underwent planned distal pancreatectomy between 2008 and 2020 in French high volume centers. Patients with cirrhosis were matched 1:4 for demographic, surgical, and histologic criteria with patients without cirrhosis. The primary endpoint was severe morbidity (Clavien-Dindo grade ≥III). The secondary endpoints were postoperative complications, specifically related to cirrhosis and pancreatic surgery, and survival for patients with pancreatic adenocarcinoma. RESULTS: Overall, 32 patients with cirrhosis were matched with 128 patients without cirrhosis. Most patients (93.5%) had Child-Pugh A cirrhosis. The severe morbidity rate after distal pancreatectomy was higher in patients with cirrhosis than in those without cirrhosis (28.13% vs 25.75%, P = .11. The operative time was significantly longer in the cirrhotic group compared with controls (P = .01). However, patients with and without cirrhosis had comparable blood loss and conversion rates. Postoperatively, the two groups had similar rates of pancreatic fistula, hemorrhage, reoperation, postoperative mortality, and survival rates at 1, 3, and 5 years. CONCLUSION: The current study suggests that distal pancreatectomy in high-volume centers is feasible for patients with compensated cirrhosis.
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Cirrose Hepática , Pancreatectomia , Neoplasias Pancreáticas , Complicações Pós-Operatórias , Humanos , Pancreatectomia/efeitos adversos , Masculino , Feminino , Estudos Retrospectivos , Pessoa de Meia-Idade , Idoso , Cirrose Hepática/complicações , Cirrose Hepática/cirurgia , Cirrose Hepática/mortalidade , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Neoplasias Pancreáticas/cirurgia , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/complicações , Resultado do Tratamento , Duração da Cirurgia , Taxa de Sobrevida , Adenocarcinoma/cirurgia , Adenocarcinoma/mortalidade , Adenocarcinoma/complicaçõesRESUMO
(1) Background: Understanding uterine innervation, an essential aspect of female reproductive biology, has often been overlooked. Nevertheless, the complex architecture of uterine innervation plays a significant role in conditions such as endometriosis. Recently, advances in histological techniques have provided unprecedented details about uterine innervation, highlighting its intricate structure, distribution, and density. The intricate nature of uterine innervation and its influence on pathologies such as endometriosis has garnered increasing attention. (2) Objectives: This review aims to compile, analyze, and summarize the existing research on uterine innervation, and investigate its implications for the pathogenesis of endometriosis and associated pain. (3) Methods: A systematic review was conducted in line with PRISMA guidelines. Using the PubMed database, we searched relevant keywords such as "uterine innervation", "endometriosis", and "pain association". (4) Results: The initial literature search yielded a total of 3300 potential studies. Of these, 45 studies met our inclusion criteria and were included in the final review. The analyzed studies consistently demonstrated that the majority of studies focused on macroscopic dissection of uterine innervation for surgical purposes. Fewer studies focused on micro-innervation for uterine innervation. For endometriosis, few studies focused on neural pain pathways whereas many studies underlined an increase in nerve fiber density within ectopic endometrial tissue. This heightened innervation is suggested as a key contributor to the chronic pain experienced by endometriosis patients. (5) Conclusions: The understanding of uterine innervation, and its alterations in endometriosis, offer promising avenues for research and potential treatment.
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PURPOSE: Pelvic gynecological surgeries, whether for malignant or benign conditions, frequently result in functional complications due to injuries to the autonomic nervous system. Recognizing the deep uterine vein (DUV) as an essential anatomical reference can aid in preserving these structures. Despite its significance, the DUV is infrequently studied and lacks comprehensive documentation in Terminologia Anatomica. This research endeavors to elucidate a detailed characterization of the DUV. METHODS: We undertook a systematic literature review aligning with the "PRISMA" guidelines, sourcing from PUBMED and EMBASE. Our comprehensive anatomical examination encompassed cadaveric dissections and radio-anatomical evaluations utilizing the Anatomage® Table. RESULTS: The literary exploration revealed a consensus on the DUV's description based on both anatomical and surgical observations. It arises from the merger of cervical, vesical, and vaginal veins, coursing through the paracervix in a descending and rearward direction before culminating in the internal iliac vein. The hands-on anatomical study further delineated the DUV's associations throughout its course, highlighting its role in bifurcating the uterus's lateral aspect into two distinct zones: a superior vascular zone housing the uterine artery and ureter and an inferior nervous segment below the DUV representing the autonomic nerve pathway. CONCLUSION: A profound understanding of the subperitoneal space anatomy is paramount for pelvic surgeons to mitigate postoperative complications. The DUV's intricate neurovascular interplays underscore its significance as an indispensable surgical guide for safeguarding nerves and the ureter.
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Útero , Humanos , Feminino , Útero/irrigação sanguínea , Útero/anatomia & histologia , Pelve/inervação , Pelve/irrigação sanguínea , Pelve/anatomia & histologia , Cadáver , Veias/anatomia & histologia , Procedimentos Cirúrgicos em Ginecologia/métodosRESUMO
OBJECTIVE: The aim of this study was to evaluate the efficacy of yttrium-90 transarterial radioembolization (TARE) to convert to resection initially unresectable, single, large (≥5 cm) hepatocellular carcinoma (HCC). BACKGROUND: TARE can downsize cholangiocarcinoma to resection but its role in HCC resectability remains debatable. METHODS: All consecutive patients with a single large HCC treated between 2015 and 2020 in a single tertiary center were reviewed. When indicated, patients were either readily resected (upfront surgery) or underwent TARE. TARE patients were converted to resection (TARE surgery) or not (TARE-only). To further assess the effect of TARE on the long-term and short-term outcomes, a propensity score matching analysis was performed. RESULTS: Among 216 patients, 144 (66.7%) underwent upfront surgery. Among 72 TARE patients, 20 (27.7%) were converted to resection. TARE-surgery patients received a higher mean yttrium-90 dose that the 52 remaining TARE-only patients (211.89±107.98 vs 128.7±36.52 Gy, P <0.001). Postoperative outcomes between upfront-surgery and TARE-surgery patients were similar. In the unmatched population, overall survival at 1, 3, and 5 years was similar between upfront-surgery and TARE-surgery patients (83.0%, 60.0%, 47% vs 94.0%, 86.0%, 55.0%, P =0.43) and compared favorably with TARE-only patients (61.0%, 16.0% and 9.0%, P <0.0001). After propensity score matching, TARE-surgery patients had significantly better overall survival than upfront-surgery patients ( P =0.021), while disease-free survival was similar ( P =0.29). CONCLUSION: TARE may be a useful downstaging treatment for unresectable localized single large HCC providing comparable short-term and long-term outcomes with readily resectable tumors.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/radioterapia , Carcinoma Hepatocelular/cirurgia , Neoplasias Hepáticas/radioterapia , Neoplasias Hepáticas/cirurgia , Estudos Retrospectivos , Radioisótopos de Ítrio/uso terapêuticoRESUMO
BACKGROUND: Given the scarce donor supply, an increasing number of so-called marginal or extended criteria donor (ECD) organs are used for liver transplantation. These ECD liver grafts are however known to be associated with a higher rate of early allograft dysfunction and primary non-function because of a greater vulnerability to ischemia-reperfusion injury. The end-ischemic hypothermic oxygenated machine perfusion (HOPE) technique may improve outcomes of liver transplantation with ECD grafts by decreasing reperfusion injury. METHODS: HOPExt trial is a comparative open-label, multicenter, national, prospective, randomized, controlled study, in two parallel groups, using static cold storage, the gold standard procedure, as control. The trial will enroll adult patients on the transplant waiting list for liver failure or liver cirrhosis and/or liver malignancy requiring liver transplantation and receiving an ECD liver graft from a brain-dead donor. In the experimental group, ECD liver grafts will first undergo a classical static cold (4 °C) storage followed by a hypothermic oxygenated perfusion (HOPE) for a period of 1 to 4 h. The control group will consist of the classic static cold storage which is the gold standard procedure in liver transplantation. The primary objective of this trial is to study the efficacy of HOPE used before transplantation of ECD liver grafts from brain-dead donors in reducing postoperative early allograft dysfunction within the first 7 postoperative days compared to simple cold static storage. DISCUSSION: We present in this protocol all study procedures in regard to the achievement of the HOPExt trial, to prevent biased analysis of trial outcomes and improve the transparency of the trial results. Enrollment of patients in the HOPExt trial has started on September 10, 2019, and is ongoing. TRIAL REGISTRATION: ClinicalTrials.gov NCT03929523. Registered on April 29, 2019, before the start of inclusion.
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Transplante de Fígado , Traumatismo por Reperfusão , Adulto , Humanos , Transplante de Fígado/efeitos adversos , Transplante de Fígado/métodos , Estudos Prospectivos , Preservação de Órgãos/efeitos adversos , Doadores de Tecidos , Fígado/patologia , Traumatismo por Reperfusão/etiologia , Traumatismo por Reperfusão/prevenção & controle , Perfusão/efeitos adversos , Perfusão/métodos , Sobrevivência de EnxertoRESUMO
BACKGROUND: With a mortality rate of up to 30%, post-pancreatectomy hemorrhage (PPH) remains a serious complication after pancreatoduodenectomy (PD) for cancer. Little is known about the long-term survival of patients after PPH. This retrospective study aimed to evaluate the impact of PPH on long-term survival after PD. METHODS: The study included 830 patients (PPH, n = 101; non-PPH, n = 729) from two centers, who underwent PD for oncological indications. PPH was defined as any bleeding event occurring within 90 days after surgery. A flexible parametric survival model was used to determine the evolution of the risk of death over time. RESULTS: At postoperative day 90, PPH significantly increased the mortality rate (PPH vs. non-PPH: 19.8% vs. 3.7%, p < 0.0001) and severe postoperative complication rate (85.1% vs. 14.1%, p < 0.0001), and decreased median survival (18.6 months vs. 30.1 months, p = 0.0001). PPH was associated with an increased mortality risk until the sixth postoperative month. After this 6-month period, PPH had no more influence on mortality. CONCLUSIONS: PPH had a negative impact on the short-term overall survival beyond postoperative day 90 and up to six months after PD. However, compared to non-PPH patients, this adverse event had no impact on mortality after a 6-month period.
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BACKGROUND: It is unclear whether preoperative biliary drainage (PBD) by endoscopic retrograde cholangiopancreatography (ERCP) is equivalent to electrocautery-enhanced lumen-apposing metal stent (ECE-LAMS) before pancreatoduodenectomy (PD). METHODS: Patients who underwent PBD for distal malignant biliary obstruction (DMBO) followed by PD were retrospectively included in nine expert centers between 2015 and 2022. ERCP or endoscopic ultrasound-guided choledochoduodenostomy with ECE-LAMS were performed. In intent-to-treat analysis, patients drained with ECE-LAMS were considered the study group (first-LAMS group) and those drained with conventional transpapillary stent the control group (first-cannulation group). The rates of technical success, clinical success, drainage-related complications, surgical complications, and oncological outcomes were analyzed. RESULTS: Among 156 patients, 128 underwent ERCP and 28 ECE-LAMS in first intent. The technical and clinical success rates were 83.5% and 70.2% in the first-cannulation group versus 100% and 89.3% in the first-LAMS group (p = 0.02 and p = 0.05, respectively). The overall complication rate over the entire patient journey was 93.7% in first-cannulation group versus 92.0% in first-LAMS group (p = 0.04). The overall endoscopic complication rate was 30.5% in first-cannulation group versus 17.9% in first-LAMS group (p = 0.25). The overall complication rate after PD was higher in the first-cannulation group than in the first-LAMS group (92.2% versus 75.0%, p = 0.016). Overall survival and progression-free survival did not differ between the groups. CONCLUSIONS: PBD with ECE-LAMS is easier to deploy and more efficient than ERCP in patients with DMBO. It is associated with less surgical complications after pancreatoduodenectomy without compromising the oncological outcome.
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Coledocostomia , Colestase , Humanos , Coledocostomia/efeitos adversos , Pancreaticoduodenectomia/efeitos adversos , Estudos de Coortes , Estudos Retrospectivos , Colestase/etiologia , Colestase/cirurgia , Stents/efeitos adversos , Endossonografia , Colangiopancreatografia Retrógrada Endoscópica/efeitos adversos , Drenagem/efeitos adversos , Ultrassonografia de IntervençãoRESUMO
BACKGROUND: Factors excluding postoperative pancreatic fistula (POPF), facilitating early drain removal and hospital discharge represent a novel approach in patients undergoing enhanced recovery after pancreatic surgery. This study aimed to establish the relevance of neutrophil-to-lymphocyte ratio (NLR) in excluding POPF after pancreatoduodenectomy (PD). METHODS: A prospectively maintained database of patients who underwent PD at two high-volume centres was used. Patients were divided into three cohorts (training, internal, and external validation). The primary endpoints of this study were accuracy, optimal timing, and cutoff values of NLR for excluding POPF after PD. RESULTS: From 2012 to 2020, in a 2:1 ratio, 451 consecutive patients were randomly sampled as training (n = 301) and validation (n = 150) cohorts. Additionally, the external validation cohort included 197 patients between 2018 and 2020. POPF was diagnosed in 135 (20.8 per cent) patients. The 90-day mortality rate was 4.1 per cent. NLR less than 8.5 on postoperative day 3 (OR, 95 per cent c.i.) was significantly associated with the absence of POPF in the training (2.41, 1.19 to 4.88; P = 0.015), internal validation (5.59, 2.02 to 15.43; P = 0.001), and external validation (5.13, 1.67 to 15.76; P = 0.004) cohorts when adjusted for relevant clinical factors. Postoperative outcomes significantly differed using this threshold. CONCLUSION: NLR less than 8.5 on postoperative day 3 may be a simple, independent, cost-effective, and easy-to-use criterion for excluding POPF.
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Fístula Pancreática , Pancreaticoduodenectomia , Complicações Pós-Operatórias , Humanos , Neutrófilos , Pâncreas/cirurgia , Fístula Pancreática/diagnóstico , Fístula Pancreática/etiologia , Pancreaticoduodenectomia/efeitos adversos , Complicações Pós-Operatórias/prevenção & controleRESUMO
BACKGROUND: In the current setting of organ shortage, brain-dead liver donors with recent liver trauma (RLT) represent a potential pool of donors. Yet, data on feasibility and safety of liver transplantation (LT) using grafts with RLT are lacking. METHODS: All liver grafts from brain-dead donors with RLT proposed for LT between 2010 and 2018 were identified from the nationwide CRISTAL registry of the Biomedicine Agency. The current study aimed at evaluating 1-y survival as the primary endpoint. RESULTS: Among 11 073 LTs, 142 LTs (1.3%) using grafts with RLT were performed. These 142 LTs, including 23 split LTs, were performed from 131 donors (46.1%) of 284 donors with RLT proposed for LT. Transplanted grafts were procured from donors with lower liver enzymes levels ( P < 0.001) and less advanced liver trauma according to the American Association for the Surgery of Trauma liver grading system ( P < 0.001) compared with not transplanted grafts. Before allocation procedures, 20 (7%) of 284 donors underwent damage control intervention. During transplantation, specific liver trauma management was needed in 19 patients (13%), consisting of local hemostatic control (n = 15), partial hepatic resection on back-table (n = 3), or perihepatic packing (n = 1). Ninety-day mortality and severe morbidity rates were 8.5% (n = 12) and 29.5% (n = 42), respectively. One-year overall and graft survival rates were 85% and 81%, and corresponding 5-y rates were 77% and 72%, respectively. CONCLUSIONS: Using liver grafts from donors with RLT seems safe with acceptable long-term outcomes. All brain-dead patients with multiorgan trauma, including liver injury, should be considered for organ allocation.
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Transplante de Fígado , Obtenção de Tecidos e Órgãos , Ferimentos não Penetrantes , Humanos , Transplante de Fígado/efeitos adversos , Fígado , Doadores de Tecidos , Ferimentos não Penetrantes/etiologia , Aloenxertos , Sobrevivência de Enxerto , Estudos RetrospectivosRESUMO
BACKGROUND: Bacteriobilia may increase the rate of deep infectious complications (DIC) after pancreaticoduodenectomy. To better adjust prophylactic and empirical antibacterial treatment, we aimed to characterize bacteriobilia in patients with preoperative endoprosthesis, and its association with postoperative DIC. METHODS: All patients who underwent pancreaticoduodenectomy in our center between 2010 and 2019 were included. The association between microbiological findings from bile samples, and postoperative DIC was analyzed, and we compared microbiology data between 2010-2014 and 2015-2019 periods. RESULTS: We enrolled 578 patients (median age 67 years [59-72], 58.7% males), of whom 220 (38.1%) had preoperative biliary endoprosthesis, with 197 (89.5%) positive preoperative bile samples pathogens were Enterobacterales, enterococci, and Candida albicans. The incidence of DIC was similar in patients with or without endoprosthesis (20.4% vs 17.8%, P = .352). Bacterial isolates collected during 2015-2019 were more resistant to cefotaxime than those recovered from 2010-2014 (45.5% vs 25.5%, P = .009). The only independent risk factor for DIC in patients with endoprosthesis was cefotaxime resistance in bile (hazard ratio 3.027 [1.115-8.216], P = .03). CONCLUSIONS: The incidence of DIC is high after pancreaticoduodenectomy, with or without endoprosthesis, despite routine postoperative treatment. Cefotaxime resistance, the only independent predictor of DIC in patients with endoprosthesis, has increased over time. Hence, cefotaxime may no longer be an appropriate empirical treatment.
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Bile , Pancreaticoduodenectomia , Masculino , Humanos , Idoso , Feminino , Pancreaticoduodenectomia/efeitos adversos , Bile/microbiologia , Cefotaxima , Cuidados Pré-Operatórios , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/prevenção & controle , Próteses e Implantes , Estudos Retrospectivos , DrenagemRESUMO
OBJECTIVE: Defining robust and standardized outcome references for distal pancreatectomy (DP) by using Benchmark analysis. BACKGROUND: Outcomes after DP are recorded in medium or small-sized studies without standardized analysis. Therefore, the best results remain uncertain. METHODS: This multicenter study included all patients undergoing DP for resectable benign or malignant tumors in 21 French expert centers in pancreas surgery from 2014 to 2018. A low-risk cohort defined by no significant comorbidities was analyzed to establish 18 outcome benchmarks for DP. These values were tested in high risk, minimally invasive and benign tumor cohorts. RESULTS: A total of 1188 patients were identified and 749 low-risk patients were screened to establish Benchmark cut-offs. Therefore, Benchmark rate for mini-invasive approach was ≥36.8%. Benchmark cut-offs for postoperative mortality, major morbidity grade ≥3a and clinically significant pancreatic fistula rates were 0%, ≤27%, and ≤28%, respectively. The benchmark rate for readmission was ≤16%. For patients with pancreatic adenocarcinoma, cut-offs were ≥75%, ≥69.5%, and ≥66% for free resection margins (R0), 1-year disease-free survival and 3-year overall survival, respectively. The rate of mini-invasive approach in high-risk cohort was lower than the Benchmark cut-off (34.1% vs ≥36.8%). All Benchmark cut-offs were respected for benign tumor group. The proportion of benchmark cases was correlated to outcomes of DP. Centers with a majority of low-risk patients had worse results than those operating complex cases. CONCLUSION: This large-scale study is the first benchmark analysis of DP outcomes and provides robust and standardized data. This may allow for comparisons between surgeons, centers, studies, and surgical techniques.
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Adenocarcinoma , Neoplasias Pancreáticas , Humanos , Pancreatectomia/métodos , Benchmarking , Adenocarcinoma/cirurgia , Pâncreas/cirurgia , Estudos Retrospectivos , Complicações Pós-Operatórias/etiologia , Resultado do TratamentoRESUMO
Background: to date, long-term outcomes of R1 vascular (R1vasc) and R1 parenchymal (R1par) resections in the setting of intrahepatic cholangiocarcinoma (iCCA) have been examined in only one study which did not find significant difference. Patients and Methods: we analyzed consecutive patients who underwent iCCA resection between 2000 and 2019 in two tertiary French medical centers. We report overall survival (OS) and disease-free-survival (DFS). Univariate and multivariate analyses were performed to determine associated factors. Results: 195 patients were analyzed. The number of R0, R1par and R1vasc patients was 128 (65.7%), 57 (29.2%) and 10 (5.1%), respectively. The 1- and 2-year OS rates in the R0, R1par and R1vasc groups were 83%, 87%, 57% and 69%, 75%, 45%, respectively (p = 0.30). The 1- and 2-year DFS rates in the R0, R1par and R1vasc groups were 58%, 50%, 30% and 43%, 28%, 10%, respectively (p = 0.019). Resection classification (HR 1.56; p = 0.003) was one of the independent predictors of DFS in multivariate analysis. Conclusions: the survival outcomes after R1par resection are intermediate to those after R0 or R1vasc resection. R1vasc resection should be avoided in patients with iCCA as it does not provide satisfactory oncological outcomes.
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Because of a narrow therapeutic index and a wide inter- and intra-patient variability, therapeutic drug monitoring of the immunosuppressant drug tacrolimus (TAC) based on whole-blood concentrations (Cblood) is mandatory in solid organ transplant recipients. Using peripheral blood mononuclear cells concentrations (CPBMC) could improve patient outcomes. The poor correlation between Cblood and CPBMC makes hypothesize that drug transporters are implicated in the intracellular accumulation of TAC. The aim of this work was therefore to clinically study: i) the role of genetic variants and ii) the effect of mRNA and protein expression of 4 drug transporters on the TAC CPBMC/blood ratio. In addition, functional in vitro experiments were performed to mechanistically validate the clinical observations. Genetic variants of ABCB1/P-gp and SLC28A3/CNT3 did not influence TAC CPBMC in liver transplant recipients (LTR). ABCC2/MRP2 at the mRNA level; ABCB1/P-gp, SLC28A3/CNT3 and SLC29A1/ENT1 at the protein level; correlated with the CPBMC/blood in kidney and LTR. In vitro results suing transporter-expressing cells confirmed that TAC is substrate of P-gp but not MRP2, whereas experiments remained inconclusive for CNT3 and ENT1. In conclusion, the genetic-transcription-protein-functional approach presented in this work provides new insights in the understanding of TAC transport at the T lymphocyte plasma membrane.
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Transplante de Fígado , Tacrolimo , Humanos , Leucócitos Mononucleares/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Citocromo P-450 CYP3A/metabolismo , Linfócitos T , Imunossupressores , RimRESUMO
OBJECTIVE: The aim of the study was to evaluate the impact of the use of a reinforced stapler (RS) during distal pancreatectomy (DP) on postoperative outcomes. BACKGROUND: DP remains associated with significant postoperative morbidity owing to pancreatic fistula (PF). To date, there is no consensus on the management of the pancreatic stump. The use of an RS potentially represents a simple way to decrease the rate of PF. METHODS: The REPLAY study (NCT03030170) is a prospective, multicenter, randomized study. Patients who underwent DP were randomized (1:1 ratio) in 2 groups for the use of a standard stapler (SS) or an RS to close remnant pancreatic parenchyma. The primary endpoint was the rate of overall PF. Secondary endpoints included severity of PF, length of hospital stay, overall morbidity, and rate of readmission for a PF within 90 days. Participants were blinded to the procedure actually carried out. RESULTS: A total of 199 were analyzed (SS, n=99; RS, n=100). One patient who did not undergo surgery was excluded. Baseline characteristics were comparable in both groups. The rate of overall PF was higher in RS group (SS: 67.7%, RS: 83%, P =0.0121), but the rate of clinically relevant PF was similar (SS: 11.1%, RS: 14%, P =0.5387). Mean length of total hospital stay, readmission for PF, postoperative morbidity, and mortality at 90 days were similar. CONCLUSION: The results of this randomized clinical trial did not favor the use of RS during DP to reduce the rate of PF.
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Pancreatectomia , Fístula Pancreática , Humanos , Pâncreas/cirurgia , Pancreatectomia/métodos , Fístula Pancreática/epidemiologia , Fístula Pancreática/etiologia , Fístula Pancreática/prevenção & controle , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/cirurgia , Estudos Prospectivos , Fatores de RiscoRESUMO
OBJECTIVE: To define benchmark cutoffs for redo liver transplantation (redo-LT). BACKGROUND: In the era of organ shortage, redo-LT is frequently discussed in terms of expected poor outcome and wasteful resources. However, there is a lack of benchmark data to reliably evaluate outcomes after redo-LT. METHODS: We collected data on redo-LT between January 2010 and December 2018 from 22 high-volume transplant centers. Benchmark cases were defined as recipients with model of end stage liver disease (MELD) score ≤25, absence of portal vein thrombosis, no mechanical ventilation at the time of surgery, receiving a graft from a donor after brain death. Also, high-urgent priority and early redo-LT including those for primary nonfunction (PNF) or hepatic artery thrombosis were excluded. Benchmark cutoffs were derived from the 75th percentile of the medians of all benchmark centers. RESULTS: Of 1110 redo-LT, 373 (34%) cases qualified as benchmark cases. Among these cases, the rate of postoperative complications until discharge was 76%, and increased up to 87% at 1-year, respectively. One-year overall survival rate was excellent with 90%. Benchmark cutoffs included Comprehensive Complication Index CCI ® at 1-year of ≤72, and in-hospital and 1-year mortality rates of ≤13% and ≤15%, respectively. In contrast, patients who received a redo-LT for PNF showed worse outcomes with some values dramatically outside the redo-LT benchmarks. CONCLUSION: This study shows that redo-LT achieves good outcome when looking at benchmark scenarios. However, this figure changes in high-risk redo-LT, as for example in PNF. This analysis objectifies for the first-time results and efforts for redo-LT and can serve as a basis for discussion about the use of scarce resources.
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Doença Hepática Terminal , Transplante de Fígado , Obtenção de Tecidos e Órgãos , Benchmarking , Doença Hepática Terminal/cirurgia , Sobrevivência de Enxerto , Humanos , Estudos Retrospectivos , Resultado do TratamentoRESUMO
In situ normothermic regional perfusion (NRP) and ex situ normothermic machine perfusion (NMP) aim to improve the outcomes of liver transplantation (LT) using controlled donation after circulatory death (cDCD). NRP and NMP have not yet been compared directly. In this international observational study, outcomes of LT performed between 2015 and 2019 for organs procured from cDCD donors subjected to NRP or NMP commenced at the donor center were compared using propensity score matching (PSM). Of the 224 cDCD donations in the NRP cohort that proceeded to asystole, 193 livers were procured, resulting in 157 transplants. In the NMP cohort, perfusion was commenced in all 40 cases and resulted in 34 transplants (use rates: 70% vs. 85% [p = 0.052], respectively). After PSM, 34 NMP liver recipients were matched with 68 NRP liver recipients. The two cohorts were similar for donor functional warm ischemia time (21 min after NRP vs. 20 min after NMP; p = 0.17), UK-Donation After Circulatory Death risk score (5 vs. 5 points; p = 0.38), and laboratory Model for End-Stage Liver Disease scores (12 vs. 12 points; p = 0.83). The incidence of nonanastomotic biliary strictures (1.5% vs. 2.9%; p > 0.99), early allograft dysfunction (20.6% vs. 8.8%; p = 0.13), and 30-day graft loss (4.4% vs. 8.8%; p = 0.40) were similar, although peak posttransplant aspartate aminotransferase levels were higher in the NRP cohort (872 vs. 344 IU/L; p < 0.001). NRP livers were more frequently allocated to recipients suffering from hepatocellular carcinoma (HCC; 60.3% vs. 20.6%; p < 0.001). HCC-censored 2-year graft and patient survival rates were 91.5% versus 88.2% (p = 0.52) and 97.9% versus 94.1% (p = 0.25) after NRP and NMP, respectively. Both perfusion techniques achieved similar outcomes and appeared to match benchmarks expected for donation after brain death livers. This study may inform the design of a definitive trial.