A review to honor the historical contributions of pauline gross, aldred warthin, and henry lynch in the description and recognition of inheritance in colorectal cancer / Uma revisão para honrar as contribuições históricas de pauline gross, aldred warthin e henry lynch na descrição e reconhecimento da hereditariedade no câncer colorretal

ABSTRACT The present manuscript aimed to review the historical development and most important contributions regarding Lynch Syndrome since its first description, more than a century ago. In 1895, a reputed pathologist from Michigan University, Dr. Aldred Scott Warthin, got intrigued by the family history of a local seamstress called Pauline Gross. According to her prevision, she would present an early death due to cancer, which actually happened (from the uterus). Historically, her family was designated "Family G", comprising a group recognized as the longest and most detailed cancer genealogy that has ever been studied. Warthin concluded that its members had genetic susceptibility for cancer, and they are, nowadays, considered the first reported Lynch Syndrome family. At that time, however, the medical cancer community was far less receptive to the association between heredity and cancer, despite the description of other families with similar heredograms. Unfortunately, this historical fact remained somewhat dormant until another investigator inaugurated a new era in the understanding of family cancer clusters. After reports and studies from this family and many others, the condition initially called Cancer Family Syndrome was changed to the eponym Lynch Syndrome. This was a recognition of the extensive and dedicated work developed by Dr. Henry Lynch in describing various characteristics of the disease, and his efforts to establish the correct recommendations for its diagnosis and treatment. Although the future announces there is still far to go for a complete understanding of Lynch Syndrome, the remarkable contributions of Pauline's intuition, Warthin's perseverance, and Lynch's work consistency must never be forgotten by those who already have or will still benefit from this knowledge.

RESUMO O objetivo do presente manuscrito foi fazer uma revisão histórica do desenvolvimento e das mais importantes contribuições em relação à Síndrome de Lynch, desde sua primeira descrição há mais de um século atrás. Em 1895, o reputado patologista Dr. Aldred Scott Warthin ficou intrigado com a história familiar de uma costureira local, chamada Pauline Gross. De acordo com a sua previsão, ela morreria precocemente devido a um câncer, o que realmente aconteceu (do útero). Historicamente, sua família foi designada como Família "G", caracterizando um grupo reconhecido como a maior e mais longa árvore genealógica relacionada ao câncer familiar jamais estudada. Warthin concluiu que os membros dessa família tinham susceptibilidade genética para câncer, e ainda hoje são considerados a primeira família com Síndrome de Lynch reportada na literatura. Entretanto, naquela época a comunidade médica oncológica não era receptiva à associação entre hereditariedade e câncer, a despeito da descrição de outras famílias com heredogramas similares. Infelizmente, esse fato histórico permaneceu esquecido até que outro investigador inaugurou uma nova era para a melhor compreensão da agregação familiar do câncer. Após diversas descrições dessa mesma agregação de casos de câncer em outras famílias, essa condição inicialmente denominada Síndrome de Câncer Familial foi mudada para o epônimo Síndrome de Lynch. Esse foi um reconhecimento ao extenso e dedicado trabalho desenvolvido pelo Dr. Henry Lynch na descrição de diversas características da doença e seus esforços para estabelecer as recomendações corretas para o seu diagnóstico e tratamento. Embora o futuro anuncie que ainda teremos um longo caminho a percorrer para a completa compreensão da Síndrome de Lynch, as contribuições extraordinárias da intuição de Pauline, da perseverança de Warthin e da consistência do trabalho de Lynch nunca devem ser esquecidas por àqueles que já se beneficiaram, bem como os que ainda irão se beneficiar de todo esse conhecimento.

Modelos pré-clínicos de câncer hepático / Preclinical models of liver câncer

ABSTRACT Background: This manuscript provides an overview of liver carcinogenesis in murine models of hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA). Objective: A review through MEDLINE and EMBASE was performed to assess articles until August 2022. Methods: Search was conducted of the entire electronic databases and the keywords used was HCC, CCA, carcinogenesis, animal models and liver. Articles exclusion was based on the lack of close relation to the subject. Carcinogenesis models of HCC include HCC induced by senescence in transgenic animals, HCC diet-induced, HCC induced by chemotoxicagents, xenograft, oncogenes, and HCC in transgenic animals inoculated with B and C virus. The models of CCA include the use of dimethylnitrosamine (DMN), diethylnitrosamine (DEN), thioacetamide (TAA), and carbon tetrachloride (CCl4). CCA murine models may also be induced by: CCA cells, genetic manipulation, Smad4, PTEN and p53 knockout, xenograft, and DEN-left median bile duct ligation. Results: In this review, we described different murine models of carcinogenesis that reproduce the key points for HCC and CCA genesis allowing a better understanding of its genetic, physiopathological, and environmental abnormalities. Conclusion: Each model has its advantages, disadvantages, similarities, and differences with the corresponding human disease and should be chosen according to the specificity of the study. Ultimately, those models can also be used for testing new anticancer therapeutic approaches.

RESUMO Contexto: Este manuscrito fornece uma visão geral da carcinogênese hepática em modelos murinos de carcinoma hepatocelular (CHC) e colangiocarcinoma (CCA). Objetivo: Realizar uma revisão de artigos científicos até agosto de 2022 utilizando as bases de dados MEDLINE e EMBASE. Métodos: A busca foi realizada em todas as bases de dados eletrônicas e as palavras-chave usadas foram CHC, CCA, carcinogenesis, modelos animais e fígado. A exclusão dos artigos baseou-se na falta de estreita relação com o assunto. Os modelos de carcinogênese do CHC incluíram: CHC induzido por senescência em animais transgênicos, CHC induzido por dieta, CHC induzido por agentes quimiotóxicos, xenoenxerto, oncogenes e CHC em animais transgênicos inoculados com vírus B e C. Os modelos de CCA incluíram: o uso de dimetilnitrosamina (DMN), dietilnitrosamina (DEN), tioacetamida (TAA) e tetracloreto de carbono (CCl4). Os modelos murinos de CCA induzidos por incluir: células de CCA, manipulação genética, animais nocaute para Smad4, PTEN e p53, xenoenxerto e ligadura do ducto biliar mediano esquerdo. Resultados: Nesta revisão, descrevemos diferentes modelos murinos de carcinogênese que reproduzem os pontos-chave para a gênese do CHC e do CCA, permitindo uma melhor compreensão de suas anormalidades genéticas, fisiopatológicas e ambientais. Conclusão: Cada modelo tem suas vantagens, desvantagens, semelhanças e diferenças com a doença humana correspondente e deve ser escolhido de acordo com a especificidade do estudo. Em última análise, esses modelos também podem ser utilizados para testar novas abordagens terapêuticas anticancerígenas.

The optimum level of meld to minimize the mortality on liver transplantation waiting list, and liver transplanted patient in são paulo state, brazil / Melhor nível do meld para minimizar a mortalidade em lista de transplante de fígado no estado de são paulo, brasil

ABSTRACT BACKGROUND: After validation in multiple types of liver disease patients, the MELD score was adopted as a standard by which liver transplant candidates with end-stage liver disease were prioritized for organ allocation in the United States since 2002, and in Brazil, since 2006. AIMS: To analyze the mortality profile of patients on the liver transplant waiting list correlated to MELD score at the moment of transplantation. METHODS: This study used the data from the Secretary of Health of the São Paulo State, Brazil, which listed 22,522 patients, from 2006 (when MELD score was introduced in Brazil) until June 2009. Patients with acute hepatic failure and tumors were included as well. We also considered the mortality of both non-transplanted and transplanted patients as a function of the MELD score at presentation. RESULTS: Our model showed that the best MELD score for patients on the liver transplant waiting list associated to better results after liver transplantation was 26. CONCLUSIONS: We found that the best score for applying to liver transplant waiting list in the State of São Paulo was 26. This is the score that minimizes the mortality in both non-transplanted and liver transplanted patients.

RESUMO RACIONAL: Desde 2002, após validação em múltiplos tipos de hepatopatias, o escore MELD foi adotado como padrão pelo qual os candidatos a transplante de fígado com doença hepática terminal têm sido priorizados para alocação de órgãos nos Estados Unidos, e em 2006 no Brasil. OBJETIVOS: Analisar a mortalidade de pacientes em lista de espera para transplante de fígado correlacionando com o MELD, no momento do transplante. MÉTODOS: Foram utilizados os dados da Secretaria de Saúde do Estado de São Paulo, Brasil, onde foram listados 22.522 pacientes, desde 2006 (quando o escore MELD foi introduzido no Brasil) até junho de 2009. Foram incluídos pacientes com falência hepática e tumores. A mortalidade de pacientes não transplantados e transplantados também foi considerada em função do escore MELD. RESULTADOS: Nosso modelo mostrou que o melhor valor do MELD, em pacientes em lista de espera para transplante e com melhores resultados, foi de 26. Este valor minimiza mortalidade em pacientes não transplantados bem comem pacientes na lista de espera para transplante de fígado. CONCLUSÕES: O escore MELD ótimo para entrar na lista de espera para transplante de fígado, no estado de São Paulo, é em torno de 26. Esse é o valor que minimiza a mortalidade tanto dos pacientes não transplantados em lista de espera, quanto dos submetidos à transplante de fígado.

Preoperative chemotherapy versus upfront surgery for advanced gastric cancer: a propensity score matching analysis / Quimioterapia pré-operatória versus cirurgia de princípio para câncer gástrico avançado: análise por escore de propensão

ABSTRACT BACKGROUND: Surgical resection remains the main curative therapeutic modality for advanced gastric cancer. Recently, the association of preoperative chemotherapy has allowed the improvement of results without increasing surgical complications. AIMS: To evaluate the surgical and oncological outcomes of preoperative chemotherapy in a real-world setting. METHODS: A retrospective review of gastric cancer patients who underwent gastrectomy was performed. Patients were divided into two groups for analysis: upfront surgery and preoperative chemotherapy. The propensity score matching analysis, including 9 variables, was applied to adjust for potential confounding factors. RESULTS: Of the 536 patients included, 112 (20.9%) were referred for preoperative chemotherapy. Before the propensity score matching analysis, the groups were different in terms of age, hemoglobin level, node metastasis at clinical stage- status, and extent of gastrectomy. After the analysis, 112 patients were stratified for each group. Both were similar for all variables assigned in the score. Patients in the preoperative chemotherapy group had less advanced postoperative p staging (p=0.010), postoperative n staging (p<0.001), and pTNM stage (p<0.001). Postoperative complications, 30- and 90-days mortality were similar between both groups. Before the propensity score matching analysis, there was no difference in survival between the groups. After the analysis, patients in the preoperative chemotherapy group had better overall survival compared to upfront surgery group (p=0.012). Multivariate analyses demonstrated that American Society of Anesthesiologists III/IV category and the presence of lymph node metastasis were factors significantly associated with worse overall survival. CONCLUSIONS: Preoperative chemotherapy was associated with increased survival in gastric cancer. There was no difference in the postoperative complication rate and mortality compared to upfront surgery.

RESUMO RACIONAL: A ressecção cirúrgica continua sendo a principal modalidade terapêutica curativa para o câncer gástrico avançado. Recentemente, a associação de quimioterapia pré-operatória tem permitido a melhora dos resultados sem aumentar as complicações cirúrgicas. OBJETIVOS: Avaliar os resultados cirúrgicos e oncológicos da quimioterapia pré-operatória em um cenário do mundo real. MÉTODOS: Realizou-se uma revisão retrospectiva de pacientes com câncer gástrico submetidos à gastrectomia. Os pacientes foram divididos em dois grupos para análise: cirurgia inicial e quimioterapia pré-operatória. A análise por escore de propensão, incluindo 9 variáveis, foi aplicada para ajustar possíveis fatores de confusão. RESULTADOS: Dos 536 pacientes incluídos, 112 (20,9%) foram encaminhados para quimioterapia pré-operatória. Antes da análise por escore de propensão, os grupos eram diferentes em termos de idade, nível de hemoglobina, status de node metastasis at clinical stage e extensão da gastrectomia. Após a análise, 112 pacientes foram estratificados para cada grupo. Ambos foram semelhantes para todas as variáveis atribuídas no escore. O grupo da quimioterapia pré-operatória apresentou estágios postoperative p staging (p=0,010), postoperative n staging (p<0,001) e pTNM menos avançados (p<0,001). As complicações pós-operatórias e a mortalidade em 30 e 90 dias foram semelhantes entre os grupos. Antes da análise por escore de propensão, não houve diferença na sobrevida entre os dois grupos. Após a análise, o grupo da quimioterapia pré-operatória apresentou melhor sobrevida global em comparação ao grupo da cirurgia inicial (p=0,012). As análises multivariadas demostraram que a categoria American Society of Anesthesiologists III/IV e a metástase linfonodal foram fatores significativamente associados à pior sobrevida global. CONCLUSÕES: A quimioterapia pré-operatória foi associada à maior sobrevida no câncer gástrico. Não houve diferença na taxa de complicações pós-operatórias e mortalidade em comparação com a cirurgia inicial.

Palliative gastrectomy versus gastric bypass for symptomatic clinical stage iv gastric cancer: a propensity score matching analysis / Gastrectomia paliativa versus derivação gástrica no câncer gástrico sintomático estadio clínico iv: uma análise empregando escore de propensão

ABSTRACT BACKGROUND: Patients with clinical stage IV gastric cancer may require palliative procedures to manage complications such as obstruction. However, there is no consensus on whether performing palliative gastrectomy compared to gastric bypass brings benefits in terms of survival. AIMS: To compare the overall survival of patients with distal obstructive gastric cancer undergoing palliative surgical treatment, using propensity score matching analysis. METHODS: Patients who underwent palliative bypass surgery (gastrojejunostomy or partitioning) and resection between the years 2009 and 2023 were retrospectively selected. Initial and postoperative clinicopathological variables were collected. RESULTS: 150 patients were initially included. The derived group (n=91) presented more locally invasive disease (p<0.01), greater degree of obstruction (p<0.01), and worse clinical status (p<0.01), while the resected ones (n= 59) presented more distant metastasis (p<0.01). After matching, 35 patients remained in each group. There was no difference in the incidence of postoperative complications, but the derived group had higher 90-day mortality (p<0.01). Overall survival was 16.9 and 4.5 months for the resected and derived groups, respectively (p<0.01). After multivariate analysis, hypoalbuminemia (hazard ratio — HR=2.02, 95% confidence interval — 95%CI 1.17-3.48; p=0.01), absence of adjuvant chemotherapy (HR=5.97; 95%CI 3.03-11.7; p<0.01), and gastric bypass (HR=3,28; 95%CI 1.8-5.95; p<0.01) were associated with worse survival. CONCLUSIONS: Palliative gastrectomy was associated with greater survival and lower postoperative morbidity compared to gastric bypass. This may be due to better local control of the disease, with lower risks of complications and better effectiveness of chemotherapy.

RESUMO RACIONAL: Pacientes com câncer gástrico estádio clínico IV podem necessitar de procedimentos paliativos para o manejo de complicações como a obstrução. Contudo, não há consenso se a realização de gastrectomia paliativa em comparação à derivação gástrica traz benefícios em termos de sobrevida. OBJETIVOS: Comparar a sobrevida global de pacientes com câncer gástrico obstrutivo distal submetidos a tratamento cirúrgico paliativo, empregando a análise com pareamento por escore de propensão. MÉTODOS: Foram selecionados retrospectivamente pacientes submetidos à cirurgia paliativa de derivação (gastrojejunostomia ou partição) e ressecção entre os anos de 2009 e 2023. Variáveis clínico-patológicas iniciais e pós-operatórias foram coletadas. RESULTADOS: Foram inicialmente incluídos 150 pacientes. O grupo derivado (n=91) apresentou mais doença localmente invasiva (p<0,01), maior garu de obstrução (p<0,01) e pior status clínico (p<0,01), enquanto os gastrectomizados (n=59) mais metástase à distância (p<0,01). Após o pareamento, restaram 35 pacientes em cada grupo. Não houve diferença na incidência de complicações pós-operatórias, mas o grupo derivado apresentou maior mortalidade em 90 dias (p<0,01). A sobrevida global foi de 16,9 e 4,5 meses para o grupo ressecado e derivado, respectivamente (p<0,01). Após análise multivariada, hipoalbuminemia (HR=2,02; IC95% 1,17-3,48; p=0,01), ausência de quimioterapia adjuvante (HR=5,97; IC95% 3,03-11,7; p<0,01) e bypass gástrico (HR =3,28; IC95% 1,8-5,95; p<0,01) foram associados a pior sobrevida. CONCLUSÕES: A gastrectomia paliativa esteve associada a maior sobrevida e menor morbidade pós-operatória quando comparada à derivação gástrica. Isto pode se dever a um melhor controle local da doença, com menores riscos de complicações e melhor efetividade da quimioterapia.

What is the role of heat shock protein in abdominal organ transplantation?

ABSTRACT Ischemia-reperfusion injury is a pathophysiological event occuring after abdominal organ transplantation, and has a significant influence on prognosis and survival of the graft. It is involved in delaying the primary function or non-functioning of the graft. The objective of this study was to provide information on heat shock protein mechanisms in ischemia-reperfusion injuries in abdominal organ transplantations, and to indicate the possible factors involved that may influence the graft outcome. Several classes of heat shock proteins are part of the ischemia and reperfusion process, both as inflammatory agonists and in protecting the process. Studies involving heat shock proteins enhance knowledge on ischemia-reperfusion injury mitigation processes and the mechanisms involved in the survival of abdominal grafts, and open space to support therapeutic future clinical studies, minimizing ischemia and reperfusion injuries in abdominal organ transplantations. Expression of heat shock proteins is associated with inflammatory manifestations and ischemia-reperfusion injuries in abdominal organ transplantations and may influence graft outcomes.

Hepatocellular carcinoma (HCC) in patients with Non-Alcoholic Fatty Liver Disease (NAFLD): screening, treatment and survival analysis in a Brazilian series

Abstract Objective: The aim of the present study was to evaluate the clinical features, Hepatocellular Carcinoma (HCC) screening, treatment modalities, and Overall Survival (OS) in a series of Non-Alcoholic Fatty Liver Disease-Related Hepatocellular Carcinoma (NAFLD-HCC) Brazilian patients. Methods: This was a cross-sectional study at the Instituto do Cancer do Estado de São Paulo, at the Faculdade de Medicina da Universidade de São Paulo with the approval of the local research ethics committee. NAFLD patients with HCC diagnosed, from May 2010 to May 2019, were included. Results: A total of 131 patients were included. Risk factors for NAFLD were present in 94.7% of the patients. Only 29% of patients were in the HCC screening program before diagnosis. HCC treatment was performed in 84.7% of patients. Cumulative survival at the end of the first year was 72%, second-year 52%, and fifth-year 32%. HCC screening before diagnosis was not significantly associated with higher cumulative survival. The independent factors associated with shorter general survival were BCLC C-D, p < 0.001, and the size of the largest nodule > 42 mm, p = 0.039. Conclusions: Although the efficacy of screening in our population regarding overall survival was hampered due to the sample size (29% had screening), BCLC stages C‒D and the size of the largest nodule larger than 42 mm were identified as independent factors of worse prognosis.

Two decades of liver resection with a multidisciplinary approach in a single institution: What has changed? Analysis of 1409 cases

Abstract Objectives: To evaluate results of patients undergoing liver resection in a single center over the past two decades with a particular look at Colorectal Liver Metastasis (CRLM) and Hepatocellular Carcinoma (HCC). Method: Patients were divided into two eras, from 2000 to 2010 (Era 1) and 2011 to 2020 (Era 2). The most frequent diagnosis was CRLM and HCC, with 738 (52.4%) and 227 (16.1%) cases respectively. An evaluation of all liver resection cases and a subgroup analysis of both CRLM and HCC were performed. Preoperative and per operative variables and long-term outcomes were evaluated. Results: 1409 liver resections were performed. In Era 2 the authors observed higher BMI, more: minimally invasive surgeries, Pringle maneuvers, and minor liver resections; and less transfusion, less ICU necessity, and shorter length of hospital stay. Severe complications were observed in 14.7% of patients, and 90-day mortality was 4.2%. Morbidity and mortality between eras were not different. From 738 CRLM resections, in Era 2 there were significantly more patients submitted to neoadjuvant chemotherapy, bilateral metastases, and smaller sizes with significantly less transfusion, the necessity of ICU, and shorter length of hospital stay. More pedicle clamping, minimally invasive surgeries, and minor resections were also observed. From 227 HCC resections, in Era 2 significantly more minimally invasive surgeries, fewer transfusions, less necessity of ICU, and shorter length of hospital stay were observed. OS was not different between eras for CRLM and HCC. Conclusions: Surgical resection in a multidisciplinary environment remains the cornerstone for the curative treatment of primary and metastatic liver tumors.

The impact of hepatitis E infection on hepatic fibrosis in liver transplanted patients for hepatitis C infection

ABSTRACT Hepatitis E Virus (HEV) is an infection known worldwide for its asymptomatic and self-limited course in most cases. Some cases progressing to chronicity have been described in immunosuppressed patients, especially in recipients of solid organ transplants. We evaluated laboratory parameters of HEV infection (HEV RNA, anti-HEV IgM and anti-HEV IgG) through enzyme-linked immunosorbent assay (Elisa), confirmed by immunoblotting, in a cohort of 294 patients who received liver transplants at the HCFMUSP (Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo). Laboratory and demographic data were collected from the entirety of the transplanted population. Hepatic biopsies of 122 patients transplanted due liver failure secondary to hepatitis C (HCV), with or without serological or molecular markers of HEV, were analyzed according to METAVIR score. Out of 24 (8.2%) patients tested positive for anti-HEV IgG, six (2%) were positive for anti-HEV IgM and 17 (5.8%) for HEV RNA. Of the patients transplanted because of HCV infection, 95 (77.8%) had received treatment including ribavirin for at least six months before blood sample collection. Among patients transplanted due to HCV cirrhosis who tested positive for anti-HEV IgG, only three (37.5%) showed fibrosis beyond stage 2, while five (41.7%) of the HEV RNA-positive patients had liver fibrosis beyond stage 2. Overall, the prevalence of HEV in the post-hepatic transplant scenario appears to be low, and, at least histologically, seemingly not harmful. We conclude that, although some studies reported a risk of HEV chronification, patients who had their livers transplanted due to HCV and showed serological or molecular markers of HEV did not have higher levels of fibrosis compared to patients who showed no indications of HEV infection at the time of the analysis.

COVID-19-related hospital cost-outcome analysis: The impact of clinical and demographic factors

ABSTRACT Introduction: Although patients' clinical conditions have been shown to be associated with coronavirus disease (COVID-19) severity and outcome, their impact on hospital costs are not known. This economic evaluation of COVID-19 admissions aimed to assess direct and fixed hospital costs and describe their particularities in different clinical and demographic conditions and outcomes in the largest public hospital in Latin America, located in São Paulo, Brazil, where a whole institute was exclusively dedicated to COVID-19 patients in response to the pandemic. Methods: This is a partial economic evaluation performed from the hospitaĺs perspective and is a prospective, observational cohort study to assess hospitalization costs of suspected and confirmed COVID-19 patients admitted between March 30 and June 30, 2020, to Hospital das Clínicas of the University of São Paulo Medical School (HCFMUSP) and followed until discharge, death, or external transfer. Microand macro-costing methodologies were used to describe and analyze the total cost associated with each patient's underlying medical conditions, itinerary and outcomes as well as the cost components of different hospital sectors. Results: The average cost of the 3254 admissions (51.7% of which involved intensive care unit stays) was US$12,637.42. The overhead cost was its main component. Sex, age and underlying hypertension (US$14,746.77), diabetes (US$15,002.12), obesity (US$18,941.55), chronic renal failure (US$15,377.84), and rheumatic (US$17,764.61), hematologic (US $15,908.25) and neurologic (US$15,257.95) diseases were associated with higher costs. Age strata >69 years, reverse transcription polymerase chain reaction (RT-PCR)-confirmed COVID-19, comorbidities, use of mechanical ventilation or dialysis, surgery and outcomes remained associated with higher costs. Conclusion: Knowledge of COVID-19 hospital costs can aid in the development of a comprehensive approach for decision-making and planning for future risk management.

Management of hepatocellular carcinoma during the COVID-19 pandemic - São Paulo Clínicas liver cancer group multidisciplinary consensus statement

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.

Evaluation of the therapeutic effect of methylene blue on the liver of rats submitted to ischemia and reperfusion

Purpose:To analyze the effect of methylene blue (MB) therapy during the liver ischemia-reperfusion injury (I/R) process.Methods:Thirty-five male Wistar rats were used, (70%) submitted to partial ischemia (IR) or not (NIR) (30%) were obtained from the same animal. These animals were divided into six groups: 1) Sham (SH), 2) Sham with MB (SH-MB); 3) I/R, submitted to 60 minutes of partial ischemia and 15 minutes of reperfusion; 4) NI/R, without I/R obtained from the same animal of group I/R; 5) I/R-MB submitted to I/R and MB and 6) NI/R-MB, without I/R. Mitochondrial function was evaluated. Osmotic swelling of mitochondria as well as the determination of malondialdehyde (MDA) was evaluated. Serum (ALT/AST) dosages were also performed. MB was used at the concentration of 15mg/kg, 15 minutes before hepatic reperfusion. Statistical analysis was done by the Mann Whitney test at 5%.Results:State 3 shows inhibition in all ischemic groups. State 4 was increased in all groups, except the I/R-MB and NI/R-MB groups. RCR showed a decrease in all I/R and NI/R groups. Mitochondrial osmotic swelling showed an increase in all I/R NI/R groups in the presence or absence of MB. About MDA, there was a decrease in SH values in the presence of MB and this decrease was maintained in the I/R group. AST levels were increased in all ischemic with or without MB.Conclusions:The methylene blue was not able to restore the mitochondrial parameters studied. Also, it was able to decrease lipid peroxidation, preventing the formation of reactive oxygen species.(AU)

Continence changes following transanal endoscopic microsurgery result from the impact on rectal capacity: clinical and functional evaluation before and after surgical treatment / Alterações da continência após microcirurgia endoscópica transanal resultam do impacto sobre a capacidade retal: avaliação clínica e funcional antes e após tratamento cirúrgico

ABSTRACT Introduction: Described in 1983 and with a stable clinical application, the impact of Transanal Endoscopic Microsurgery on anorectal function remains unknown. The objectives of the present study were to evaluate the impact of Transanal Endoscopic Microsurgery on anorectal function according to clinical (Wexner score) and functional (anorectal manometry) evaluations before and after surgery. Method: Prospectively, 23 consecutive patients with rectal lesions were operated using TEO® equipment (Karl Storz, Tuttlingen, Germany). For all patients, the value of Wexner score was obtained before and after surgery (7, 30 and 90 days) and anorectal electromanometry was performed before surgery, and also postoperatively (30 and 90 days). Results: Fourteen patients were men. The mean age was 53.7 (24-81) years. The mean distance from the lesion to the pectineal line was 7 (2-15) cm. The histopathologic analysis revealed adenoma in 14 (61%); neuroendocrine tumor in 5 (21.7%); invasive carcinoma in 3 (13%); and hyperplastic polyp in 1 (4.3%) case. The mean duration of postoperative follow-up was 5 (3-7) months. Wexner score was significantly lower at 30 days compared to 7 days (Wilcoxon; p = 0.03). Rectal capacity was significantly lower 30 days after surgery and recovered at 90 days of surgery (ANOVA; p = 0.04). Conclusions: After Transanal Endoscopic Microsurgery, a modest impact on anorectal function can be observed. The transient impairment results from loss of rectal capacity and not from impairment of the anal sphincters, being completely resolved 90 days after surgery.

RESUMO Introdução: Descrita em 1983 e de sólida aplicação clínica, o impacto da Microcirurgia Endoscópica Transanal sobre a função anorretal permanece pouco conhecido. Os objetivos do presente estudo foram avaliar o impacto da Microcirurgia Endoscópica Transanal na função anorretal conforme avaliações clínica (Wexner score) e funcional (manometria anorretal) antes e após a cirurgia. Método: Prospectivamente, 23 pacientes consecutivos com lesões retais foram operados com o uso do equipamento TEO® (Karl Storz, Tuttlingen, Alemanha). Para todos os pacientes, o valor do escore de Wexner foi obtido antes e após a cirurgia (7, 30 e 90 dias) e a eletromanometria anorretal foi realizada antes da cirurgia e também no pós-operatório (30 e 90 dias). Resultados: Quatorze pacientes eram homens. A idade média foi 53,7 (24-81) anos. A distância média da lesão à linha pectínea foi de 7 (2-15) cm. A histopatológica revelou adenoma em 14 (61%), tumor neuroendócrino em 5 (21,7%); carcinoma invasivo em 3 (13%) e pólipo hiperplásico em 1 (4,3%) caso. A duração média do seguimento pós-operatório foi de 5 (3-7) meses. O escore de Wexner foi significativamente menor aos 30 dias em comparação com 7 dias (Wilcoxon; p = 0,03). A capacidade retal foi significativamente menor aos 30 dias após a cirurgia e recuperada aos 90 dias após a cirurgia (ANOVA; p = 0,04). Conclusões: Após Microcirurgia Endoscópica Transanal, um impacto modesto na função anorretal pode ser observado. O comprometimento transitório resulta de perda de capacidade retal e não por comprometimento dos esfíncteres anais cessando completamente 90 dias após a cirurgia.