WELLINGTON ANDRAUS
Projetos de Pesquisa
Unidades Organizacionais
Instituto Central, Hospital das Clínicas, Faculdade de Medicina
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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- Liver transplantation in gastroenteropancreatic neuroendocrine tumors(2023) FERNANDES, Eduardo de Souza M.; KYT, Camila V. Garcia; MELLO, Felipe Pedreira Tavares de; PIMENTEL, Leandro Savattone; ANDRADE, Ronaldo de Oliveira; GIRAO, Camila; CESAR, Camilla; SIQUEIRA, Munique; MONACHESI, Maria Eduarda; BRITO, Anderson; SOUSA, Claudia Cristina Tavares de; ANDRAUS, Wellington; TORRES, Orlando Jorge M.Neuroendocrine tumors are part of a heterogeneous group of tumors located in organs such as the gastrointestinal tract (GIT), lungs, thymus, thyroid, and adrenal glands. The most prevalent sites are the small intestine, cecal appendix, and pancreas. More than 50% of these tumors are associated with metastases at the time of diagnosis. Neuroendocrine tumors are classified according to the degree of cell differentiation and the histopathological proliferation index of the lesion. Neuroendocrine tumors can be well differentiated or poorly differentiated. G3 tumors are characterized by Ki-67 expression greater than 20% and can be either well differentiated (G3 NET) or poorly differentiated (G3 NEC). Neuroendocrine carcinoma (NEC G3) is subdivided into small-cell and large-cell types. When neuroendocrine tumors present clinical and compressive symptoms, carcinoid syndrome is evident. Carcinoid syndrome occurs when the tumor produces neuroendocrine mediators that cannot be metabolized by the liver due to either the size of the tumor or their secretion by the liver itself. Several therapeutic strategies have been described for the treatment of metastatic neuroendocrine tumors, including curative or palliative surgical approaches, peptide receptor radionuclide therapy, percutaneous therapy, systemic chemotherapy, and radiotherapy. Liver surgery is the only approach that can offer a cure for metastatic patients. Liver metastases must be completely resected, and in this context, orthotopic liver transplantation has gained prominence for yielding very promising outcomes in selected cases. The aim of this study is to review the literature on OLT as a form of treatment with curative intent for patients with gastroenteropancreatic neuroendocrine tumors with liver metastasis.
- 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.
- Registry of the International Society of Uterus Transplantation: First Report(2023) BRANNSTROM, Mats; TULLIUS, Stefan G.; BRUCKER, Sara; DAHM-KAHLER, Pernilla; FLYCKT, Rebecca; KISU, Iori; ANDRAUS, Wellington; WEI, Li; CARMONA, Francisco; AYOUBI, Jean-Marc; SCOLLO, Paolo; WEYERS, Steven; FRONEK, JiriBackground.Uterus transplantation (UTx) is a novel type of transplantation to treat infertility in women with an absent or nonfunctioning uterus. The International Society of Uterus Transplantation (ISUTx) has developed a registry to monitor worldwide UTx activities while serving as a repository for specific research questions. Methods.The web-based registry has separate data fields for donor, recipient, surgeries, immunosuppression, rejections, pregnancies with live birth(s), and transplant hysterectomies. Data are prospectively registered. Results.A total of 45 UTx procedures have been registered; the majority (78%) of those procedures were live donor (LD) transplants. Median age of the LDs, deceased donors, and recipients were 50 y (range 32-62), 38.5 y (19-57), and 29 y (22-38), respectively. The duration of LD surgery was approximately twice as long as the recipient surgery. Postoperative complications of any Clavien-Dindo grade were registered in 20% of LDs and 24% of recipients. Rejection episodes were more frequent (33%) early after transplantation (months 1-5) compared with later time points (months 6-10; 21%). Healthy neonates were delivered by 16 recipients, with 3 women giving birth twice. The total live birth rate per embryo transfer was 35.8%. Median length of pregnancy was 35 gestational weeks. Twelve uteri were removed without childbirth, with 9 transplant hysterectomies occurring during the initial 7 mo post-UTx. Conclusions.A mandatory registry is critical to determine quality and process improvement for any novel transplantation. This registry provides a detailed analysis of 45 UTx procedures performed worldwide with a thorough analysis of outcomes and complications.
conferenceObject PER ORAL CHOLANGIOSCOPY (POCS) IN LIVER TRANSPLANT PATIENTS: A PROSPECTIVE, INTERNATIONAL SERIES(2022) FRANZINI, Tomazo; MOURA, Eduardo G. De; CARDENAS, Andres; SLIVKA, Adam; WERNER-POLEY, Jan; PAPACHRISTOU, Georgios; RABINOVITZ, Mordechai; BRUNO, Marco J.; PEETERMANS, Joyce A.; ROUSSEAU, Matthew; YIN, Srey; ANDRAUS, Wellington; EMOND, Jean; SETHI, Amrita- Cirrhosis and hernia repair in a cohort of 6352 patients in a tertiary hospital Risk assessment and survival analysis(2022) PIPEK, Leonardo Zumerkorn; CORTEZ, Vitor Santos; TABA, Joao Victor; SUZUKI, Milena Oliveira; NASCIMENTO, Fernanda Sayuri do; MATTOS, Vitoria Carneiro de; MORAES, Walter Augusto; IUAMOTO, Leandro Ryuchi; HSING, Wu Tu; CARNEIRO-D'ALBUQUERQUE, Luiz Augusto; MEYER, Alberto; ANDRAUS, WellingtonThe prevalence of hernias in patient with cirrhosis can reach up to 40%. The pathophysiology of cirrhosis is closely linked to that of the umbilical hernia, but other types are also common in this population. The aim of this study is to evaluate factors that influence in the prognosis after hernia repair in patients with cirrhosis. A historical cohort of 6419 patients submitted to hernia repair was gathered. Clinical, epidemiological data and hernia characteristics were obtained. For patient with cirrhosis, data from exams, surgery and follow-up outcomes were also analyzed. Survival curves were constructed to assess the impact of clinical and surgical variables on survival. 342 of the 6352 herniated patients were cirrhotic. Patient with cirrhosis had a higher prevalence of umbilical hernia (67.5% x 24.2%, P<.001) and a lower prevalence of epigastric (1.8% x 9.0%, P<.001) and lumbar (0% x 0.18%, P=.022). There were no significant differences in relation to inguinal hernia (P=.609). Ascites was present in 70.1% of patient with cirrhosis and its prevalence was different in relation to the type of hernia (P<.001). The survival curve showed higher mortality for emergency surgery, MELD>14 and ascites (HR 12.6 [3.79-41.65], 4.5 [2.00-10.34], and 6.1 [1.15-20.70], respectively, P<.05). Hernia correction surgery in patient with cirrhosis has a high mortality, especially when performed under urgent conditions associated with more severe clinical conditions of patients, such as the presence of ascites and elevated MELD.
- Immunomodulatory response in an experimental model of brain death(2023) SANTANA, Alexandre Chagas; ANDRAUS, Wellington; OBERMAN, Dan Zimelewicz; RABELO, Nicollas Nunes; SILVA, Filipe Miranda Oliveira; DELLE, Humberto; PEPINELI, Rafael; MORAES, Edvaldo Leal de; SCAVONE, Cristoforo; LIMA, Larissa de Sa; DEGASPARI, Sabrina; BRASIL, Sergio; SOLLA, Davi Jorge Fontoura; RUIZ, Liliane Moreira; OLIVEIRA-BRAGA, Karina Andrighetti de; NEPOMUCENO, Natalia Aparecida; PEGO-FERNANDES, Paulo Manuel; TULLIUS, Stefan Gunther; FIGUEIREDO, Eberval GadelhaLiver transplantation has come a long way and is now regarded as the gold standard treatment for end-stage liver failure. The great majority of livers utilized in transplantation come from brain-dead donors. A broad inflammatory response characterizes BD, resulting in multiorgan damage. This process is primarily mediated by cytokines, which increase the immunogenicity of the graft. In male Lewis rats, we evaluated the immune response in a BD liver donor and compared it to that of a control group. We studied two groups: Control and BD (rats subjected to BD by increasing intracranial pressure). After the induction of BD, there was an intense rise in blood pressure followed by a fall. There were no significant differences observed between the groups. Blood tissue and hepatic tissue analyzes showed an increase in plasma concentrations of liver enzymes (AST, ALT, LDH and ALP), in addition to pro-inflammatory cytokines and macrophages in liver tissue in animals submitted to BD. The current study found that BD is a multifaceted process that elicits both a systemic immune response and a local inflammatory response in liver tissue. Our findings strongly suggested that the immunogenicity of plasma and liver increased with time following BD.
- Cholangioscopy-guided steroid injection for refractory post liver transplant anastomotic strictures: a rescue case series(2019) FRANZINI, Tomazo; SAGAE, Vitor M. T.; GUEDES, Hugo G.; SAKAI, Paulo; WAISBERG, Daniel R.; ANDRAUS, Wellington; D'ALBUQUERQUE, Luiz A. C.; SETHI, Amrita; MOURA, Eduardo G. H. deBackground and aims: Post liver transplant biliary anastomotic strictures have traditionally been treated with balloon dilation and multiple plastic stents. Fully covered self-expandable metallic stents may be used as an initial alternative or after multiple plastic stents failure. Refractory strictures can occur in 10-22% and require revisional surgery. Alternatively, cholangioscopy allows direct visualization and therapeutic approaches. We aimed to assess the feasibility, safety, and efficacy of balloon dilation combined with cholangioscopy-guided steroid injection for the treatment of refractory anastomotic biliary strictures. Methods: Three post-orthotopic liver transplant patients who failed standard treatment of their biliary anastomotic strictures underwent endoscopic retrograde cholangiopancreatography with balloon dilation followed by cholangioscopy-guided steroid injection at a tertiary care center. Patients had follow-up with images and laboratorial tests to evaluate for residual stricture. Results: Technical success of balloon dilation+cholangioscopy-guided steroid injection was achieved in all patients. Cholangioscopy permitted accurate evaluation of bile ducts and precise localization for steroid injection. No adverse events occurred. Mean follow-up was 26 months. Two patients are stent free and remain well in follow-up, with no signs of biliary obstruction. No further therapeutic endoscopic procedures or revisional surgery were required. One patient did not respond to balloon dilation+cholangioscopy-guided steroid injection after 11 months of follow-up and required repeat balloon dilation of new strictures above the anastomosis. Conclusion: Cholangioscopy-guided steroid injection combined with balloon dilation in the treatment of refractory post liver transplant strictures is feasible and safe. This method may be used as a rescue alternative before surgical approach. Randomized controlled trials comparing balloon dilation+cholangioscopy-guided steroid injection to fully covered self-expandable metallic stents are needed to determine the role of this treatment for anastomotic biliary strictures.
- ACUTE CHOLECYSTITIS IN HIGH-RISK PATIENTS. SURGICAL, RADIOLOGICAL, OR ENDOSCOPIC TREATMENT? BRAZILIAN COLLEGE OF DIGESTIVE SURGERY POSITION PAPER(2023) COELHO, Julio Cezar Uili; COSTA, Marco Aurelio Raeder da; ENNE, Marcelo; TORRES, Orlando Jorge Martins; ANDRAUS, Wellington; CAMPOS, Antonio Carlos LigockiAcute 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.
- 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.
- Thalidomide modulates renal inflammation induced by brain death experimental model(2022) SANTANA, Alexandre Chagas; ANDRAUS, Wellington; SILVA, Filipe Miranda Oliveira; SALA, Ana Clara Garcia; SCHUST, Amanda Souza; NERI, Luis Henrique Metelmann; FELICIANO, Regiane; PEPINELI, Rafael; DELLE, Humberto; RUIZ, Liliane Moreira; OLIVEIRA-BRAGA, Karina Andrighetti De; NEPOMUCENO, Natalia Aparecida; PEGO-FERNANDES, Paulo Manuel; SANTOS, Marcelo Jose dos; MORAES, Edvaldo Leal de; BRASIL, Sergio; FIGUEIREDO, Eberval GadelhaBackground: Brain death (BD) is characterized by a complex inflammatory response, resulting in dysfunction of potentially transplantable organs. This process is modulated by cytokines, which amplify graft immunogenicity. We have investigated the inflammatory response in an animal model of BD and analyzed the effects of thalidomide, a drug with powerful immunomodulatory properties. Methods: BD was induced in male Lewis rats. We studied three groups: Control (sham-operated rats) (n = 6), BD (rats subjected to brain death) (n = 6) and BD + Thalid (BD rats treated with one dose of thalidomide (200 mg/ Kg), administered by gavage) (n = 6). Six hours after BD, serum levels of urea and creatinine, as well as systemic and renal tissue protein levels of TNF-alpha and IL-6, were analyzed. We also determined the mRNA expression of ET-1, and macrophage infiltration by immunohistochemistry. Results: BD induced a striking inflammatory status, demonstrated by a significant increase of plasma cytokines: TNF-alpha (2.8 +/- 4.3 pg/mL [BD] vs. 9.4 +/- 2.8 pg/mL [Control]), and IL-6 (6219.5 +/- 1380.6 pg/mL [BD] vs. 1854.7 +/- 822.6 pg/mL [Control]), and in the renal tissue: TNF-alpha (2.5 +/- 0.3 relative expression [BD] vs. 1.0 +/- 0.4 relative expression [Control]; p < 0.05), and IL-6 (4.0 +/- 0.4 relative expression [BD] vs. 1.0 +/- 0.3 relative expression [Control]; p < 0.05). Moreover, BD increased macrophages infiltration (2.47 +/- 0.07 cells/field [BD] vs. 1.20 +/- 0.05 cells/field [Control]; p < 0.05), and ET-1 gene expression (2.5 +/- 0.3 relative expression [BD] vs. 1.0 +/- 0.2 relative expression [Control]; p < 0.05). In addition, we have observed deterioration in renal function, characterized by an increase of urea (194.7 +/- 25.0 mg/dL [BD] vs. 108.0 +/- 14.2 mg/dL [Control]; p < 0.05) and creatinine (1.4 +/- 0.04 mg/dL [BD] vs. 1.0 +/- 0.07 mg/dL [Control]; p < 0.05) levels. Thalidomide administration significantly reduced plasma cytokines: TNF-alpha (5.1 +/- 1.4 pg/mL [BD + Thalid] vs. BD; p < 0.05), and IL-6 (1056.5 +/- 488.3 pg/mL [BD + Thalid] vs. BD; p < 0.05), as well as in the renal tissue: TNF-alpha (1.5 +/- 0.2 relative expression [BD + Thalid] vs. BD; p < 0.05), and IL-6 (2.1 +/- 0.3 relative expression [BD + Thalid] vs. BD; p < 0.05). Thalidomide treatment also induced a significant decrease in the expression of ET-1 (1.4 +/- 0.3 relative expression [BD + Thalid] vs. BD; p < 0.05), and macrophages infiltration (1.17 +/- 0.06 cells/field [BD + Thalid] vs. BD; p < 0.05). Also thalidomide prevented kidney function failure by reduced urea (148.3 +/- 4.4 mg/dL [BD + Thalid] vs. BD; p < 0.05), and creatinine (1.1 +/- 0.14 mg/dL [BD + Thalid] vs. BD; p < 0.05). Conclusions: The immunomodulatory properties of thalidomide were effective in decreasing systemic and local immunologic response, leading to diminished renal damage, as reflected in the decrease of urea and creatinine levels. These results suggest that use of thalidomide may represent a potential strategy for treating in BD kidney organ donors.