ABSTRACT Objective: To explain the rationale and protocol of the methods and analyses to be used in the LIVER-PAM randomized clinical trial, which seeks to understand whether a higher mean arterial pressure is capable of reducing the incidence of renal dysfunction postoperatively after liver transplantation. Methods: LIVER-PAM is an open-label, randomized, controlled, singlecenter clinical trial. Patients randomized to the intervention group will have a mean arterial pressure of 85 - 90mmHg in the initial 24 hours of postoperative management, while patients in the control group will have a mean arterial pressure of 65 - 70mmHg in the same period. A sample of 174 patients will be required to demonstrate a 20% reduction in the absolute incidence of renal dysfunction, with a power of 80% and an alpha of 0.05. Conclusion: If a 20% reduction in the absolute incidence of renal dysfunction in the postoperative period of liver transplantation is achieved with higher target mean arterial pressure in the first 24 hours, this would represent an inexpensive and simple therapy for improving current outcomes in the management of liver transplant patients. ClinicalTrials.gov Registry:NCT05068713

RESUMO Objetivo: Explicitar o racional e o protocolo de métodos e análises a serem utilizadas no ensaio clínico randomizado LIVER-PAM, que busca entender se um nível mais alto de pressão arterial média é capaz de reduzir a incidência de disfunção renal no pós-operatório de transplante hepático. Métodos: O LIVER-PAM é um estudo clínico randomizado, controlado, unicêntrico e aberto. Pacientes randomizados para o grupo intervenção terão como alvo de pressão arterial média 85 - 90mmHg nas 24 horas iniciais do manejo pós-operatório, enquanto pacientes do grupo controle terão como alvo de pressão arterial média 65 - 70mmHg no mesmo período. Uma amostra de 174 pacientes será necessária para demonstrar redução de 20% na incidência absoluta de disfunção renal, com poder de 80% e alfa de 0,05. Conclusão: Se a redução de 20% da incidência absoluta de disfunção renal no pós-operatório de transplante hepático for obtida com alvos maiores de pressão arterial média nas primeiras 24 horas, o manejo do paciente nesse cenário encontraria uma terapia barata e simples para a melhoria dos desfechos atuais. Registro Cliniclatrials.gov:NCT05068713

RESUMO A colecistite aguda (CA) é um processo inflamatório agudo da vesícula biliar que pode estar associado a complicações potencialmente graves, como empiema, gangrena, perfuração da vesícula biliar e sepse. O tratamento padrão para a CA é a colecistectomia laparoscópica. No entanto, para um pequeno grupo de pacientes com CA, o risco de colecistectomia laparoscópica pode ser muito alto, principalmente em idosos com doenças graves associadas. Nestes pacientes críticos, a colecistectomia percutânea ou a drenagem endoscópica da vesícula biliar guiada por ultrassom podem ser uma opção terapêutica temporária, como ponte para a colecistectomia. O objetivo deste artigo de posicionamento do Colégio Brasileiro de Cirurgia Digestiva é apresentar novos avanços no tratamento da CA em pacientes cirúrgicos de alto risco, para auxiliar cirurgiões, endoscopistas e clínicos a selecionar o melhor tratamento para os seus pacientes. A eficácia, segurança, vantagens, desvantagens e resultados de cada procedimento são discutidos. As principais conclusões são: a) Pacientes com CA e risco cirúrgico elevado devem ser tratados preferencialmente em hospitais terciários onde a experiência e os recursos cirúrgicos, radiológicos e endoscópicos estão disponíveis. b) A modalidade de tratamento ideal para pacientes com elevado risco cirúrgico, deve ser individualizada, com base nas condições clínicas e na experiência disponível. c) A colecistectomia laparoscópica continua sendo uma excelente opção de tratamento, principalmente em hospitais em que a drenagem da vesícula biliar percutânea ou endoscópica não está disponível. d) A colecistostomia percutânea e a drenagem endoscópica da vesícula biliar devem ser realizadas apenas em hospitais bem equipados e com radiologista intervencionista e/ou endoscopista experientes. e) O cateter de colecistostomia deve ser removido após a resolução da CA. No entanto, em pacientes que não têm condição clínica para realizar colecistectomia, o cateter pode ser mantido por um período prolongado ou mesmo definitivamente. f) Se o cateter de colecistostomia for mantido por longo período de tempo podem ocorrer várias complicações, como sangramento, fístula biliar, obstrução, dor no local de inserção, remoção acidental do cateter e CA recorrente. g) O tempo de espera ideal entre a colecistostomia e a colecistectomia ainda não foi estabelecido, e vai desde imediatamente após a melhoria clínica, até meses após. h) Longos períodos de espera entre colecistostomia e colecistectomia podem estar associados a novos episódios de CA, múltiplas readmissões hospitalares e aumento dos custos. Finalmente, ao selecionar a melhor opção de tratamento, outros aspectos também devem ser considerados, como custos, disponibilidade dos procedimentos no centro médico e o desejo do paciente. O paciente e sua família devem ser completamente informados sobre todas as opções de tratamento, para que possam ajudar a tomar a decisão final. (CA empiema gangrena sepse entanto associadas críticos temporária cirurgiões eficácia segurança vantagens discutidos disponíveis b individualizada disponível c d eou experientes definitivamente f sangramento obstrução inserção recorrente g estabelecido h custos Finalmente considerados final

ABSTRACT Acute cholecystitis (AC) is an acute inflammatory process of the gallbladder that may be associated with potentially severe complications, such as empyema, gangrene, perforation of the gallbladder, and sepsis. The gold standard treatment for AC is laparoscopic cholecystectomy. However, for a small group of AC patients, the risk of laparoscopic cholecystectomy can be very high, mainly in the elderly with associated severe diseases. In these critically ill patients, percutaneous cholecystostomy or endoscopic ultrasound gallbladder drainage may be a temporary therapeutic option, a bridge to cholecystectomy. The objective of this Brazilian College of Digestive Surgery Position Paper is to present new advances in AC treatment in high-risk surgical patients to help surgeons, endoscopists, and physicians select the best treatment for their patients. The effectiveness, safety, advantages, disadvantages, and outcomes of each procedure are discussed. The main conclusions are: a) AC patients with elevated surgical risk must be preferably treated in tertiary hospitals where surgical, radiological, and endoscopic expertise and resources are available; b) The optimal treatment modality for high-surgical-risk patients should be individualized based on clinical conditions and available expertise; c) Laparoscopic cholecystectomy remains an excellent option of treatment, mainly in hospitals in which percutaneous or endoscopic gallbladder drainage is not available; d) Percutaneous cholecystostomy and endoscopic gallbladder drainage should be performed only in well-equipped hospitals with experienced interventional radiologist and/or endoscopist; e) Cholecystostomy catheter should be removed after resolution of AC. However, in patients who have no clinical condition to undergo cholecystectomy, the catheter may be maintained for a prolonged period or even definitively; f) If the cholecystostomy catheter is maintained for a long period of time several complications may occur, such as bleeding, bile leakage, obstruction, pain at the insertion site, accidental removal of the catheter, and recurrent AC; g) The ideal waiting time between cholecystostomy and cholecystectomy has not yet been established and ranges from immediately after clinical improvement to months. h) Long waiting periods between cholecystostomy and cholecystectomy may be associated with new episodes of acute cholecystitis, multiple hospital readmissions, and increased costs. Finally, when selecting the best treatment option other aspects should also be considered, such as costs, procedures available at the medical center, and the patient’s desire. The patient and his family should be fully informed about all treatment options, so they can help making the final decision. (AC empyema gangrene sepsis However high diseases highrisk surgeons endoscopists effectiveness safety advantages disadvantages discussed radiological b highsurgicalrisk c d wellequipped well equipped andor endoscopist e definitively f occur bleeding leakage obstruction site g months h readmissions costs Finally considered center s desire options decision

ABSTRACT This study aimed to report the first case of a patient with hepatosplenic schistosomiasis mansoni, refractory ascites and portal vein thrombosis treated with a transjugular intrahepatic portosystemic shunt (TIPS), at the Instituto de Radiologia, Hospital das Clinicas, Faculdade de Medicina, Universidade de Sao Paulo, Brazil. After the procedure, the patient recovered favorably and progressed with portal pressure reduction and no deterioration of the liver function. Endovascular shunt modification is a conservative medical approach that often helps in reducing symptoms significantly, making it a less invasive and a safer alternative to liver transplantation for the treatment of schistosomiasis with portal hypertension.

Abstract Background: The Coronavirus 19 (COVID-19) pandemic has dramatically impacted liver organ transplantation. The American Society of Transplantation recommends a minimum of 28 days after symptom resolution for organ donation. However, the exact time for transplantation for recipients is unknown. Considering that mortality on the waiting list for patients with MELD >25 or fulminant hepatitis is higher than that of COVID-19, the best time for surgery after SARS-CoV-2 infection remains undetermined. This study aims to expand the current knowledge regarding the Liver Transplantation (LT) time for patients after COVID-19 and to provide transplant physicians with essential decision-making tools to manage these critically ill patients during the pandemic. Methods: Systematic review of patients who underwent liver transplantation after diagnosis of COVID-19. The MEDLINE, PubMed, Cochrane, Lilacs, Embase, and Scielo databases were searched until June 20, 2021. The MESH terms used were “COVID-19” and “Liver transplantation”. Results: 558 articles were found; of these 13 articles and a total of 18 cases of COVID-19 prior to liver transplantation were reported. The mean age was 38.7±14.6, with male prevalence. Most had mild symptoms of COVID. Five patients have specific treatment for COVID-19 with convalescent plasm or remdesivir/oseltamivir, just one patient received hydroxychloroquine, and 12 patients received only symptomatic treatment. The median time between COVID-19 to LT was 19 days (13.5-44.5). Deceased donor liver transplantation accounted for 61% of cases, while living donor transplantation was 39%. Conclusion: Despite the concerns regarding the postoperative evolution, the mortality of patients with high MELD or fulminant hepatitis transplanted shortly after COVID-19 diagnosis does not seem to be higher. (PROSPERO, registration number = CRD42021261790)

Abstract Introduction: The increase in the incidence of pancreatic and biliary cancers has attracted the search for methods of early detection of diseases and biomarkers. The authors propose to analyze new findings on the association between microbiota and Pancreatic Ductal Adenocarcinoma (PDAC) or Cholangiocarcinoma (CCA). Methods: This systematic review was carried out according to the items of Preferred Reports for Systematic Reviews and Protocol Meta-Analysis (PRISMA-P). This study was registered by the Prospective Register of Systematic Reviews (PROSPERO), identification code CRD42020192748 before the review was carried out. Articles were selected from the PUBMED, EMBASE, and Cochrane databases. Results: Most studies (86.67%) used 16s rRNA as a sequencing method. The main comorbidities found were diabetes mellitus, systemic arterial hypertension, and dyslipidemia. Many studies were limited by the small number of participants, but the biases were mostly low. There was very little concordance about the composition of the microbiome of different sites, for both case and control groups when compared to other studies’ results. Bile sample analysis was the one with a greater agreement between studies, as three out of four studies found Escherichia in cases of CCA. Conclusion: There was great disagreement in the characterization of both the microbiota of cases and control groups. Studies are still scarce, making it difficult to adequately assess the data in this regard. It was not possible to specify any marker or to associate any genus of microbiota bacteria with PDAC or CCA.

RESUMO - RACIONAL: O câncer colorretal é a terceira neoplasia mais frequente e metade dos pacientes desenvolvem metástase hepática. O melhor fator prognóstico na metástase hepática de câncer colorretal (MHCCR) é a possibilidade de ressecção com margens livres, porém a maioria permanece irressecável. O racional em realizar transplante hepático (TH) em pacientes portadores de MHCCR está na ampliação do número de pacientes ressecáveis através de uma hepatectomia total. OBJETIVO: Apresentar protocolo brasileiro para realização de transplante hepático em pacientes com MHCCR irressecável. MÉTODO: O protocolo foi realizado por duas instituições com grande volume de ressecções e transplantes hepáticos no Brasil, baseado no trabalho realizado pela Universidade de Oslo. A elaboração foi dividida em 4 etapas. RESULTADO: É apresentada proposta de protocolo para esta doença a ser validada na aplicação clínica. CONCLUSÃO: Foi possível elaborar protocolo de transplante hepático para MHCCR irressecável a fim de uniformizar o tratamento e melhor avaliar os resultados cirúrgicos.

ABSTRACT - BACKGROUND: Colorectal cancer (CRC) is the third most common neoplasm, and half of the patients with CRC develop liver metastasis. The best prognostic factor for colorectal liver metastasis (CRLM) is the possibility of performing a resection with free margins; however, most of them remain unresectable. The justification for performing liver transplantation (LT) in patients with CRLM regards an increase in the number of resectable patients by performing total hepatectomy. AIM: The aim of this study was to provide a Brazilian protocol for LT in patients with unresectable CRLM. METHOD: The protocol was carried out by two Brazilian institutions, which perform a large volume of resections and LTs, based on the study carried out at the University of Oslo. The elaboration of the protocol was conducted in four stages. RESULT: A protocol proposal for this disease is presented, which needs to be validated for clinical use. CONCLUSION: The development of an LT protocol for unresectable CRLM aims to standardize the treatment and to enable a better evaluation of surgical results.

Non-tumoral portal vein thrombosis (PVT) is associated with higher morbidity and mortality in liver transplantation (LT). In this study, we aimed to evaluate the impact of PVT in LT outcomes and analyze the types of surgical techniques used for dealing with PVT during LT. A systematic review was conducted in Cochrane, MEDLINE, and EMBASE databases, selecting articles from January 1990 to December 2019. The MESH-terms used were (“Portal Vein”[Mesh] AND “Thrombosis”[Mesh] NOT “Neoplasms”[Mesh]) AND (“Liver Transplantation”[Mesh]). The Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) recommendation was used, and meta-analysis was performed with Review Manager Version 5.3 software. A total of 1,638 articles were initially found: 488 in PubMed, 289 in Cochrane Library, and 861 in EMBASE, from which 27 were eventually selected for the meta-analysis. Surgery time of LT in patients with PVT was longer than in patients without LT (p<0.0001). Intraoperative red blood cell (p<0.00001), fresh frozen plasma (p=0.01), and platelets (p=0.03) transfusions during LT were higher in patients with PVT. One-year (odds ratio [OR] 1.17; p=0.002) and 5-year (OR 1.12; p=0.01) patient survival after LT was worse in the PVT group. Total occlusive PVT presented higher mortality (OR 3.70; p=0.00009) and rethrombosis rates (OR 3.47 [1.18-10.21]; p=0.02). PVT Yerdel III/IV classification exhibited worse 1-year [2.04 (1.21-3.42); p=0.007] and 5-year [0.98 (0.59-1.62); p=0.93] patient survival. Thrombectomy with primary anastomosis was associated with better outcomes. LT in patients with non-tumoral PVT demands more surgical time, needs more intraoperative transfusion, and presents worse 1- and 5-year patient survival. Total occlusive PVT and Yerdel III/IV PVT classification were associated with higher mortality. (PROSPERO, registration number: CRD42020132915).

A combination of immunosuppressants may improve outcomes due to the synergistic effect of their different action mechanisms. Currently, there is no consensus regarding the best immunosuppressive protocol after liver transplantation. This review aimed to evaluate the effectiveness and safety of tacrolimus associated with mycophenolate mofetil (MMF) in patients undergoing liver transplantation. We performed a systematic review and meta-analysis of randomized clinical trials. Eight randomized trials were included. The proportion of patients with at least one adverse event related to the immunosuppression scheme with tacrolimus associated with MMF was 39.9%. The tacrolimus with MMF immunosuppression regimen was superior in preventing acute cellular rejection compared with that of tacrolimus alone (risk difference [RD]=-0.11; p =0.001). The tacrolimus plus MMF regimen showed no difference in the risk of adverse events compared to that of tacrolimus alone (RD=0.7; p=0.66) and cyclosporine plus MMF (RD=-0.7; p=0.37). Patients undergoing liver transplantation who received tacrolimus plus MMF had similar adverse events when compared to patients receiving other evaluated immunosuppressive regimens and had a lower risk of acute rejection than those receiving in the monodrug tacrolimus regimen.

RESUMO Racional: A incidência de hérnia abdominal em pacientes cirróticos é elevada, em torno de 20%. Em casos de ascite volumosa, a incidência atinge valores até 40%. Uma das principais e mais graves complicações no pós-operatório de correção de hérnias de pacientes cirróticos é a insuficiência renal aguda (IRA). Objetivo: Analisar a função renal de pacientes cirróticos submetidos a herniorrafias, comparando aqueles que apresentavam IRA pós-operatório com os demais, para determinar os fatores relacionados à sua ocorrência. Método: Seguimento de pacientes cirróticos submetidos à cirurgia de hérnia entre 2001 e 2014 no Serviço de Transplante de Fígado. Foram coletados exames laboratoriais para avaliar a função renal no pós-operatório rotineiramente. A IRA foi definida com base no consenso do clube da ascite em 2015. Resultados: Dos 174 pacientes incluídos, ocorreu IRA em 58 pacientes (34,9%). Houve diferença entre grupos para as seguintes variáveis: MELD inicial, creatinina basal e creatinina, o grupo com IRA apresentou medias superiores ao grupo que não apresentou IRA. No grupo IRA PO, 74,1% das cirurgias, foram realizadas em caráter de emergência, enquanto que no grupo sem IRA no pós-operatório, 34,6%. No grupo IRA, 90,4% dos indivíduos apresentaram complicações no pós-operatório, enquanto no grupo sem IRA, 29,9%. As variáveis idade, MELD inicial, creatinina basal e creatinina no pós-operatório inicial foram estatisticamente significantes na análise de sobrevida. Conclusões: Existe uma associação entre IRA pós-operatória e cirurgia de emergência e IRA pós-operatóri e complicações pós-operatórias. Os fatores relacionados à maior ocorrência de IRA em pacientes cirróticos submetidos à cirurgia de hérnia são o MELD inicial, creatinina basal, creatinina pós-operatória inicial. O preparo de pacientes cirróticos com hérnia abdominal antes de procedimentos cirúrgicos deve ocorrer sistematicamente, pois apresentam alta incidência de IRA pós-operatória.

ABSTRACT Background: The incidence of abdominal hernia in cirrhotic patients is as higher as 20%; in cases of major ascites the incidence may increase up to 40%. One of the main and most serious complications in cirrhotic postoperative period (PO) is acute kidney injury (AKI). Aim: To analyze the renal function of cirrhotic patients undergoing to hernia surgery and evaluate the factors related to AKI. Methods: Follow-up of 174 cirrhotic patients who underwent hernia surgery. Laboratory tests including the renal function were collected in the PO.AKI was defined based on the consensus of the ascite´s club. They were divided into two groups: with (AKI PO) and without AKI . Results: All 174 patients were enrolled and AKI occurred in 58 (34.9%). In the AKI PO group, 74.1% had emergency surgery, whereas in the group without AKI PO it was only 34.6%.In the group with AKI PO, 90.4% presented complications, whereas in the group without AKI PO they occurred only in 29.9%. Variables age, baseline MELD, baseline creatinine, creatinine in immediate postoperative (POI), AKI and the presence of ascites were statistically significant for survival. Conclusions: There is association between AKI PO and emergency surgery and, also, between AKI PO and complications after surgery. The factors related to higher occurrence were initial MELD, basal Cr, Cr POI. The patients with postoperative AKI had a higher rate of complications and higher mortality.

RESUMO Racional: O colangiocarcinoma hilar representa mais da metade de todos os casos de colangiocarcinoma; tem prognóstico reservado e sobrevida global mediana de 12- 24 meses após o diagnóstico. A proposta de realizar transplante hepático surgiu para ampliar a possibilidade de margens livres através de hepatectomia total nos portadores de tumoresirressecáveis com melhor prognóstico. Objetivo: Apresentar protocolo brasileiro para realização de transplante hepático em pacientes com colangiocarcinoma hilar. Método: O protocolo foi realizado por duas instituições com grande volume de ressecções e transplantes hepáticos no Brasil, baseado no trabalho realizado pela MayoClinic. A elaboração foi dividida em quatro etapas. Resultado: É apresentada proposta de protocolo para esta doença a ser validada na aplicação clínica. Conclusão: Foi possível elaborar protocolo de transplante hepático para colangiocarcinoma a fim de uniformizar o tratamento e melhor avaliar os resultados cirúrgicos.

ABSTRACT Background: Hilar cholangiocarcinoma represents more than half of all cholangiocarcinoma cases, having poor prognosis and presenting a median overall survival after diagnosis of 12-24 months. In patients who have unresectable tumors with a better prognosis, the proposal to perform liver transplantation emerged for expanding the possibility of free margins by performing total hepatectomy. Aim: To provide a Brazilian protocol for liver transplantation in patients with hilar cholangiocarcinoma. Method: The protocol was carried out by two Brazilian institutions which perform a large volume of resections and liver transplantations, based on the study carried out at the Mayo Clinic. The elaboration of the protocol was conducted in four stages. Result: A protocol proposal for this disease is presented, which needs to be validated for clinical use. Conclusion: The development of a liver transplantation protocol for cholangiocarcinoma aims not only to standardize the treatment, but also enable a better assessment of the surgical results in the future.

More than 18 million people in 188 countries have been diagnosed as having coronavirus disease (COVID-19), and COVID-19 has been responsible for more than 600,000 deaths worldwide. Brazil is now the second most affected country globally. Faced with this scenario, various public health measures and changes in the daily routines of hospitals were implemented to stop the pandemic. Patients with hepatocellular carcinoma (HCC) are at an increased risk for severe COVID-19 as they present with two major diseases: cancer and concomitant chronic liver disease. The COVID-19 pandemic can significantly impact the management of HCC patients from diagnosis to treatment strategies. These patients need special attention and assistance at this time, especially since treatment for tumors cannot be delayed in most cases. The aim of this guideline was to standardize the management of HCC patients during the COVID-19 pandemic. This document was developed, on the basis of the best evidence available, by a multidisciplinary team from Instituto do Câncer do Estado de São Paulo (ICESP), and Instituto Central of the Hospital das Clínicas da Universidade de São Paulo (HC-FMUSP), which are members of the São Paulo Clínicas Liver Cancer Group.

Coronavirus disease (COVID-19) rapidly progresses to severe acute respiratory syndrome. This review aimed at collating available data on COVID-19 infection in solid organ transplantation (SOT) patients. We performed a systematic review of SOT patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The MEDLINE and PubMed databases were electronically searched and updated until April 20, 2020. The MeSH terms used were “COVID-19” AND “Transplant.” Thirty-nine COVID-19 cases were reported among SOT patients. The median interval for developing SARS-CoV-2 infection was 4 years since transplantation, and the fatality rate was 25.64% (10/39). Sixteen cases were described in liver transplant (LT) patients, and the median interval since transplantation was 5 years. The fatality rate among LT patients was 37.5% (6/16), with death occurring more than 3 years after LT. The youngest patient who died was 59 years old; there were no deaths among children. Twenty-three cases were described in kidney transplant (KT) patients. The median interval since transplantation was 4 years, and the fatality rate was 17.4% (4/23). The youngest patient who died was 71 years old. Among all transplant patients, COVID-19 had the highest fatality rate in patients older than 60 years : LT, 62.5% vs 12.5% (p=0.006); KT 44.44% vs 0 (p=0.039); and SOT, 52.94% vs 4.54% (p=0.001). This study presents a novel description of COVID-19 in abdominal SOT recipients. Furthermore, we alert medical professionals to the higher fatality risk in patients older than 60 years. (PROSPERO, registration number=CRD42020181299)