RAFAEL SOARES NUNES PINHEIRO
Projetos de Pesquisa
Unidades Organizacionais
Instituto Central, Hospital das Clínicas, Faculdade de Medicina - Médico
LIM/37 - Laboratório de Transplante e Cirurgia de Fígado, Hospital das Clínicas, Faculdade de Medicina
LIM/37 - Laboratório de Transplante e Cirurgia de Fígado, Hospital das Clínicas, Faculdade de Medicina
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- Translational medical research and liver transplantation: systematic review(2018) NACIF, Lucas Souto; KIM, Vera; GALVAO, Flavio; ONO, Suzane Kioko; PINHEIRO, Rafael Soares; CARRILHO, Flair Jose; D'ALBUQUERQUE, Luiz CarneiroTranslational medicine has become a priority, but there is still a big difference between the arrival of new treatments and investment. Basic science should not be neglected because the translation from basic research is not sustained in the absence of basic research. The purpose of this literature review was to analyze the translational medicine in the liver transplant field: liver ischemia-reperfusion injury (IRI), immunosuppression, clinical and surgical complications, small-for-size syndrome (SFSS), rejection, and ongoing innovations (liver machine, liver preservation, artificial livers, and regenerative medicine). We performed a systematic literature review that were updated in October 2016. The searches were performed in the Cochrane Central Register of Controlled Trials and Review, PubMed/Medline, Embase, and LILACS databases. All the selected studies on the management of translational medical research in liver transplantation (LT) were analyzed. Initially the search found 773 articles. Methodological viewing and analysis of the articles, followed by the application of scientific models, including translational medicine in the liver transplant field. In conclusions, this review demonstrates the application of scientific research with translation medical benefits regarding the LT. The literature has a great tendency, improvements and investments in the study of translational medicine in LT. Innovative studies and technologies from basic science help to clarify clinical doubts. Moreover, evidence increases the importance of scientific research in quality of clinical practice care.
- Living-donor liver transplantation in Budd-Chiari syndrome with inferior vena cava complete thrombosis: A case report and review of the literature(2021) ROCHA-SANTOS, Vinicius; WAISBERG, Daniel Reis; PINHEIRO, Rafael Soares; NACIF, Lucas Souto; ARANTES, Rubens Macedo; DUCATTI, Liliana; MARTINO, Rodrigo Bronze; HADDAD, Luciana Bertocco; GALVAO, Flavio Henrique; ANDRAUS, Wellington; CARNEIRO-D'ALBURQUERQUE, Luiz AugustoBACKGROUND Budd-Chiari syndrome (BCS) is a challenging indication for liver transplantation (LT) due to a combination of massive liver, increased bleeding, retroperitoneal fibrosis and frequently presents with stenosis of the inferior vena cava (IVC). Occasionally, it may be totally thrombosed, increasing the complexity of the procedure, as it should also be resected. The challenge is even greater when performing living-donor LT as the graft does not contain the retrohepatic IVC; thus, it may be necessary to reconstruct it. CASE SUMMARY A 35-year-old male patient with liver cirrhosis due to BCS and hepatocellular carcinoma beyond the Milan criteria underwent living-donor LT with IVC reconstruction. It was necessary to remove the IVC as its retrohepatic portion was completely thrombosed, up to almost the right atrium. A right-lobe graft was retrieved from his sister, with outflow reconstruction including the right hepatic vein and the branches of segment V and VIII to the middle hepatic vein. Owing to massive subcutaneous collaterals in the abdominal wall, venovenous bypass was implemented before incising the skin. The right atrium was reached via a transdiaphragramatic approach. Hepatectomy was performed en bloc with the retrohepatic vena cava. It was reconstructed with an infra-hepatic vena cava graft obtained from a deceased donor. The patient remains well on outpatient clinic follow-up 25 mo after the procedure, under an anticoagulation protocol with warfarin. CONCLUSION Living-donor LT in BCS with IVC thrombosis is feasible using a meticulous surgical technique and tailored strategies.
- Prevalence of chronic venous insufficiency and deep vein thrombosis in cirrhotic patients(2023) RENO, Leonardo da Cruz; TUSTUMI, Francisco; WAISBERG, Daniel Reis; SANTOS, Vinicious Rocha; PINHEIRO, Rafael Soares; MACEDO, Rubens Arantes; NACIF, Lucas Souto; DUCATTI, Liliana; MARTINO, Rodrigo Bronze De; TREVISAN, Alexandre Maximiniano; D'ALBUQUERQUE, Luiz Carneiro; ANDRAUS, WellingtonPeople with cirrhosis of the liver are at risk for complications that can worsen their quality of life and increase morbidity and mortality. Contrary to previous beliefs, cirrhosis does not protect against the development of thromboembolic events, and cirrhotic patients may have higher rates of deep vein thrombosis (DVT).Background and aims: The study of chronic venous disease and its impact on patients with cirrhosis is unknown in the literature and may be an important fact since this condition also had impact on quality of life and morbidity. The aim of this study is to evaluate the prevalence of DVT (Deep Venous thrombosis) in outpatients with cirrhosis and the degree of chronic venous insufficiency, evaluating possible correlations between clinical and laboratory aspects of cirrhotic patients with these pathologies.Methods: Patients with cirrhosis were evaluated in the outpatient clinic of the Liver Transplantation and Hepatology Service of HC-FMUSP from November 2018 to November 2022, with clinical evaluation, venous disease questionnaires, data collection of imaging and laboratory tests, and venous color Doppler ultrasound. The information was analyzed by the University of Sao Paulo (USP) Statistics Department.Results: There was a prevalence of 7.6% of DVT in studied patients, VCSS score 6.73 and severe CEAP classification (C4-6) 32.1%. There was no association of DVT with qualitative variables by the Fisher test such as Child Turcotte Pugh Scale (CTP) (p = 0.890), dichotomized INR values (p = 0.804), etiology of cirrhosis (p = 0.650) and chronic kidney disease (p > 0.999), nor with quantitative variables by t-student's such as age (p = 0.974), Body Mass Index (BMI) (p = 0.997), MELD score (p = 0.555), Albumin (p = 0.150) and Platelets (p = 0.403). We found that as the severity of ascites increases, there is an increase in the proportion of patients classified in the category indicating more severe clinical manifestations of chronic venous disease (C4 to C6). The mean age (54 years) was higher in patients with DVT than in those without. The mean BMI of patients without DVT (25.7 kg/m(2)) is lower than that of patients with DVT (27.0 kg/m(2)). The prevalence of DVT is higher in patients with thrombophilia (20.0%) than in those without (7.0%). This suggests an association between the two variables. The descriptive measures of the MELD score, the cirrhosis scale used for liver transplant waiting lists, did not indicate an association of this scale with the occurrence of DVT.Conclusion: The incidence of VTE (Venous Thromboembolic Events) and CVD (Chronic Venous Disease) within the sample surpassed that of the general population; nevertheless, more studies are required to validate these results. Concerning venous thromboembolism, no correlation was observed between the variables within the sample and the augmented risk of VTE. Regarding chronic venous disease, studies have shown that edema and orthostatism are correlated with increased severity of CVD on the VCSS scales. Statistical dispersion methods suggest that patients with higher BMI and more severe liver disease (according to the Child-Pugh score) are more likely to experience worsening of CVD. About chronic venous disease, studies have shown that edema and orthostatism are correlated with increased severity of CVD on the VCSS scales.
- Abdominal hernias in cirrhotic patients: Surgery or conservative treatment? Results of a prospective cohort study in a high volume center: Cohort study(2020) PINHEIRO, Rafael Soares; ANDRAUS, Wellington; WAISBERG, Daniel Reis; NACIF, Lucas Souto; DUCATTI, Liliana; ROCHA-SANTOS, Vinicius; DINIZ, Marcio A.; ARANTES, Rubens Macedo; LERUT, Jan; D'ALBUQUERQUE, Luiz Augusto CarneiroBackground: Surgical treatment of abdominal hernias in cirrhotics is often delayed due to the higher morbidity and mortality associated with the underlying liver disease. Some patients are followed conservatively and only operated on when complications occur (""wait and see"" approach). The aim of this study is to compare outcomes of cirrhotic patients undergoing conservative non-operative care or elective hernia repair. Methods: A prospective observational study including 246 cirrhotic patients with abdominal hernia was carried out. Patients were given the option to select their treatment: elective hernia repair or conservative non-operative care. Demographics, characteristics of underlying liver disease, type of hernia, complications and mortality were analyzed. During follow-up of patients who opted for the ""wait and see"" approach, emergency hernia repair was performed in case of hernia complications. Results: Elective hernia repair was performed in 57 patients and 189 patients were kept in conservative care, of which 43 (22.7%) developed complications that required emergency hernia repair. Elective surgery provided better five-years survival than conservative care (80% vs. 62%; p = 0.012). Multivariate analysis identified multiples hernias [Hazards Ratio (HR):6.7, p < 0.001] and clinical follow-up group (HR 3.62, p = 0.005) as risk factors for mortality. Among patients undergoing surgical treatment, multivariate analysis revealed MELD> 11 (HR 7.8; p = 0.011) and emergency hernia repair (HR 5.35; p = 0.005) as independent risk factors for 30-day mortality. Conclusions: Elective hernia repair offers an acceptable morbidity and ensures longer survival. ""Wait and see"" approach jeopardizes cirrhotic patients and should be avoided, given the higher incidence of emergency surgery due to hernia complications.
- Laparoscopic cholecystectomy and cirrhosis: patient selection and technical considerations(2017) PINHEIRO, Rafael S.; WAISBERG, Daniel R.; LAI, Quirino; ANDRAUS, Wellington; NACIF, Lucas S.; ROCHA-SANTOS, Vinicius; D'ALBUQUERQUE, Luiz A. C.The incidence of cholelithiasis in cirrhotic patients is higher than in general population. In the past, open cholecystectomy (OC) was the standard approach for patients requiring cholecystectomy. However, laparoscopic cholecystectomy (LC) was introduced in 1980's and gradually became the preferred technique even to cirrhotic patients. The performance of gastrointestinal surgery procedures in cirrhotics patients is well-known to be associated with higher technical difficulty and increased morbidity-mortality. Cirrhosis is a major key intraoperative finding that contributes to surgical difficulty in LC. Model of End Stage Liver Disease (MELD) score and Child-Pugh Classification are the best devices to evaluate the underlying liver disease and to predict morbidity-mortality. Acute cholecystitis has higher incidence in patients with cirrhosis, emergency procedures in cirrhotics patients are associated with higher morbidity, longer postoperative hospitalization and a seven-fold higher mortality in comparison to elective surgery. LC in cirrhotics has a higher conversion rate to open procedure; however, LC demonstrated substantial advantage over OC providing shorter convalescence period and hospital stay.
- Venous thromboembolism in in-hospital cirrhotic patients: A systematic review(2022) RENO, Leonardo da Cruz; TUSTUMI, Francisco; WAISBERG, Daniel Reis; ROCHA-SANTOS, Vinicius; PINHEIRO, Rafael Soares; MACEDO, Rubens Arantes; NACIF, Lucas Souto; DUCATTI, Liliana; MARTINO, Rodrigo Bronze De; TREVISAN, Alexandre Maximiliano; CARNEIRO-D'ALBUQUERQUE, Luiz; ANDRAUS, WellingtonIntroduction: Patients with liver cirrhosis are at a higher risk of hospitalization. The present review aimed to assess the risk of thromboembolism and its burden on hospitalized cirrhotic patients. Materials and methods: A systematic review (PROSPERO: CRD42021256869) was conducted in PubMed, Embase, Cochrane, Lilacs, and a manual search of references. It evaluated studies that compare cirrhotic patients with venous thromboembolism (VTE) with cirrhotic patients without VTE or studies that compare cirrhotic patients with non-cirrhotic patients. No restrictions were set for the date of publication or language. The last search was conducted in June 2021. Results: After selection, 17 studies were included from an initial search of 5,323 articles. The chronic liver disease etiologies comprise viral, alcohol, autoimmune, NASH (non-alcoholic steatohepatitis), cryptogenic, hemochromatosis, cholestasis, and drug-related. The included studies were conflicted regarding the outcomes of VTE, pulmonary embolism, or bleeding. Patients with cirrhosis associated with VTE had prolonged length of hospital stay, and patients with cirrhosis were at higher risk of portal thrombosis. Conclusion: In-hospital cirrhotic patients are a heterogeneous group of patients that may present both thrombosis and bleeding risk. Clinicians should take extra caution to apply both prophylactic and therapeutic anticoagulation strategies.
- Liver transplantation after DRESS syndrome: A case report and review of the literature(2020) CALIL, Igor Lepski; TUSTUMI, Francisco; PINHEIRO, Rafael Soares Nunes; TANIGAWA, Ryan Yukimatsu; CRUZ JUNIOR, Ruy Jorge; SOUSA, Jorge Henrique Bento de; PECORA, Rafael Antonio Arruda; D'ALBUQUERQUE, Luiz Augusto CarneiroThis study reports a patient with DRESS syndrome, associated with liver failure, treated with orthotopic liver transplantation.
- Living donor liver transplantation for hepatocellular cancer: An (almost) exclusive Eastern procedure?(2017) PINHEIRO, R. S.; WAISBERG, D. R.; NACIF, L. S.; ROCHA-SANTOS, V.; ARANTES, R. M.; DUCATTI, L.; MARTINO, R. B.; LAI, Q.; ANDRAUS, W.; DALBUQUERQUE, L. A. C.Hepatocellular carcinoma (HCC) is the fifth most prevalent cancer and it is linked with chronic liver disease. Liver transplantation (LT) is the best curative treatment modality, since it can cure simultaneously the underlying liver disease and HCC. Milan criteria (MC) are the benchmark for selecting patients with HCC for LT, achieving up to 91% 1-year survival post transplantation. However, when considering intention-to-treat (ITT) rates are substantially lower, mainly due dropout. Additionally, Milan criteria (MC) are too restrictive and more inclusive criteria have been reported with good outcomes. Mainly, in Eastern countries, deceased donors are scarce, therefore Asian centers have developed living-donor liver transplantation (LDLT) to a state-of-art status. There are many eastern centers reporting huge numbers of LDLT with outstanding results. Regarding HCC patients, they have reported many criteria including more advanced tumors achieving reasonable outcomes. Western countries have well-established deceased-donor liver transplantation (DDLT) programs. However, organ shortage and restrictive criteria for listing patients with HCC endorses LDLT as a good option to offer curative treatment to more HCC patients. However, there are some controversial reports claiming higher rates of HCC recurrence after LDLT than DDLT. An extensive review included 30 studies with cohorts of HCC patients who underwent LDLT in both East and West countries. We reported also the results of our Institution, in Brazil, where it was performed the first LDLT. This review also addresses the eligibility criteria for transplanting patients with HCC developed in Western and Eastern countries. © Translational Gastroenterology and Hepatology. All rights reserved.
- Resection for intrahepatic cholangiocellular cancer: new advances(2018) WAISBERG, Daniel R.; PINHEIRO, Rafael S.; NACIF, Lucas S.; ROCHA-SANTOS, Vinicius; MARTINO, Rodrigo B.; ARANTES, Rubens M.; DUCATTI, Liliana; LAI, Quirino; ANDRAUS, Wellington; D'ALBUQUERQUE, Luiz C.Intrahepatic cholangiocarcinoma (ICC) is the second most prevalent primary liver neoplasm after hepatocellular carcinoma (HCC), corresponding to 10% to 15% of cases. Pathologies that cause chronic biliary inflammation and bile stasis are known predisposing factors for development of ICC. The incidence and cancer-related mortality of ICC is increasing worldwide. Most patients remain asymptomatic until advance stage, commonly presenting with a liver mass incidentally diagnosed. The only potentially curative treatment available for ICC is surgical resection. The prognosis is dismal for unresectable cases. The principle of the surgical approach is a margin negative hepatic resection with preservation of adequate liver remnant. Regional lymphadenectomy is recommended at time of hepatectomy due to the massive impact on outcomes caused by lymph node (LN) metastasis. Multicentric disease, tumor size, margin status and tumor differentiation are also important prognostic factors. Staging laparoscopy is warranted in high-risk patients to avoid unnecessary laparotomy. Exceedingly complex surgical procedures, such as major vascular, extrahepatic bile ducts and visceral resections, ex vivo hepatectomy and autotransplantation, should be implemented in properly selected patients to achieve negative margins. Neoadjuvant therapy may be used in initially unresectable lesions in order to downstage and allow resection. Despite optimal surgical management, recurrence is frustratingly high. Adjuvant chemotherapy with radiation associated with locoregional treatments should be considered in cases with unfavorable prognostic factors. Selected patients may undergo re-resection of tumor recurrence. Despite the historically poor outcomes of liver transplantation for ICC, highly selected patients with unresectable disease, especially those with adequate response to neoadjuvant therapy, may be offered transplant. In this article, we reviewed the current literature in order to highlight the most recent advances and recommendations for the surgical treatment of this aggressive malignancy.
- Molecular Profile of Intrahepatic Cholangiocarcinoma(2024) ANDRAUS, Wellington; TUSTUMI, Francisco; MEIRA JUNIOR, Jose Donizeti de; PINHEIRO, Rafael Soares Nunes; WAISBERG, Daniel Reis; LOPES, Liliana Ducatti; ARANTES, Rubens Macedo; SANTOS, Vinicius Rocha; MARTINO, Rodrigo Bronze de; D'ALBUQUERQUE, Luiz Augusto CarneiroIntrahepatic cholangiocarcinoma (ICC) is a relatively uncommon but highly aggressive primary liver cancer that originates within the liver. The aim of this study is to review the molecular profile of intrahepatic cholangiocarcinoma and its implications for prognostication and decision-making. This comprehensive characterization of ICC tumors sheds light on the disease's underlying biology and offers a foundation for more personalized treatment strategies. This is a narrative review of the prognostic and therapeutic role of the molecular profile of ICC. Knowing the molecular profile of tumors helps determine prognosis and support certain target therapies. The molecular panel in ICC helps to select patients for specific therapies, predict treatment responses, and monitor treatment responses. Precision medicine in ICC can promote improvement in prognosis and reduce unnecessary toxicity and might have a significant role in the management of ICC in the following years. The main mutations in ICC are in tumor protein p53 (TP53), Kirsten rat sarcoma virus (KRAS), isocitrate dehydrogenase 1 (IDH1), and AT-rich interactive domain-containing protein 1A (ARID1A). The rate of mutations varies significantly for each population. Targeting TP53 and KRAS is challenging due to the natural characteristics of these genes. Different stages of clinical studies have shown encouraging results with inhibitors of mutated IDH1 and target therapy for ARID1A downstream effectors. Fibroblast growth factor receptor 2 (FGFR2) fusions are an important target in patients with ICC. Immune checkpoint blockade can be applied to a small percentage of ICC patients. Molecular profiling in ICC represents a groundbreaking approach to understanding and managing this complex liver cancer. As our comprehension of ICC's molecular intricacies continues to expand, so does the potential for offering patients more precise and effective treatments. The integration of molecular profiling into clinical practice signifies the dawn of a new era in ICC care, emphasizing personalized medicine in the ongoing battle against this malignancy.