Rafael S. Pinheiro

Alpha-Fetoprotein and Novel Tumor Biomarkers as Predictors of Hepatocellular Carcinoma Recurrence after Surgery: A Brilliant Star Raises Again

Alpha-fetoprotein (AFP), des-γ-carboxy prothrombin (DCP), and lens culinaris agglutinin-reactive fraction of AFP (AFP-L3) have been developed with the intent to detect hepatocellular carcinoma (HCC) and for the surveillance of at-risk patients. However, at present, none of these tests can be recommended to survey cirrhotic patients at risk for HCC development because of their suboptimal ability for routine clinical practice in HCC diagnosis. Starting from these considerations, these markers have been therefore routinely and successfully used as predictors of survival and HCC recurrence in patients treated with curative intent. All these markers have been largely used as predictors in patients treated with hepatic resection or locoregional therapies, mainly in Eastern countries. In recent studies, AFP has been proposed as predictor of recurrence after liver transplantation and as selector of patients in the waiting list. Use of AFP modification during the waiting list for LT is still under investigation, potentially representing a very interesting tool for patient selection. The development of a new predictive model combining radiological and biological features based on biological markers is strongly required. New genetic markers are continuously discovered, but they are not already fully available in the clinical practice.

Tumor growth pattern as predictor of colorectal liver metastasis recurrence

BACKGROUND Surgical resection is the gold standard therapy for the treatment of colorectal liver metastases (CRM). The aim of this study was to investigate the impact of tumor growth patterns on disease recurrence. METHODS We enrolled 91 patients who underwent CRM resection. Pathological specimens were prospectively evaluated, with particular attention given to tumor growth patterns (infiltrative vs pushing). RESULTS Tumor recurrence was observed in 65 patients (71.4%). According to multivariate analysis, 3 or more lesions (P = .05) and the infiltrative tumor margin type (P = .05) were unique independent risk factors for recurrence. Patients with infiltrative margins had a 5-year disease-free survival rate significantly inferior to patients with pushing margins (20.2% vs 40.5%, P = .05). CONCLUSIONS CRM patients with pushing margins presented superior disease-free survival rates compared with patients with infiltrative margins. Thus, the adoption of the margin pattern can represent a tool for improved selection of patients for adjuvant treatment.

Is minimal, [almost] steroid-free immunosuppression a safe approach in adult liver transplantation? Long-term outcome of a prospective, double blind, placebo-controlled, randomized, investigator-driven study

Objective:To investigate the safety of minimal immunosuppression (IS) in liver transplantation (LT). Background:The lack of long-term follow-up studies, including pathologic data, has led to a protean handling of IS in LT. Methods:Between February 2000 and September 2004, 156 adults were enrolled in a prospective, randomized, double-blind, placebo-controlled minimization trial comparing tacrolimus placebo (TAC-PLAC) and TAC short-term steroid (TAC-STER) IS. All patients had a minimum clinical, biochemical, and histological follow-up of 5 years. Results:Five-year actual patient and graft survival rates in TAC-PLAC and TAC-STER groups were 78.1% and 82.1% (P = 0.89) and 74.2% and 76.9% (P = 0.90), respectively. Five-year biopsies were available in 112 (89.6%) of 125 survivors. Twelve patients refused a biopsy because of their excellent evolution; tissue material was insufficient in 1 patient; 11 had normal liver tests; and 2 patients had developed alcoholic and secondary biliary cirrhosis. Histology was normal in 44 (39.3%) patients; 35 (31.3%) had disease recurrence. The remaining biopsies showed nonspecific chronic hepatitis (14.3%), mild inflammatory infiltrates (10.7%), and steatosis (3.5%). All findings were equally distributed between both groups. In each group, 3 patients (4.8%) presented with acute cellular rejection after the first year and only 1 (0.9%) TAC-PLAC patient developed chronic rejection after IS withdrawal because of pneumonitis. Arterial hypertension, diabetes mellitus, renal insufficiency, hypercholesterolemia, gout, and obesity were equally low in both groups. Conclusions:Excellent long-term results can be obtained under minimal IS and absence of steroids. TAC-based monotherapy is feasible in most adult liver recipients until 5 years of follow-up.

From portal to splanchnic venous thrombosis: What surgeons should bear in mind

The present study aims to review the evolution of surgical management of portal (PVT) and splanchnic venous thrombosis (SVT) in the context of liver transplantation over the last 5 decades. PVT is more commonly managed by endovenous thrombectomy, while SVT requires more complex technical expedients. Several surgical techniques have been proposed, such as extensive eversion thrombectomy, anastomosis to collateral veins, reno-portal anastomosis, cavo-portal hemi-transposition, portal arterialization and combined liver-intestinal transplantation. In order to achieve satisfactory outcomes, careful planning of the surgical strategy is mandatory. The excellent results that are obtained nowadays confirm that, even extended, splanchnic thrombosis is no longer an absolute contraindication for liver transplantation. Patients with advanced portal thrombosis may preferentially be referred to specialized centres, in which complex vascular approaches and even multivisceral transplantation are performed.

Adoption of MELD score increases the number of liver transplant

Background Liver transplantation is performed at large transplant centers worldwide as a therapeutic intervention for patients with end-stage liver diseases. Aim To analyze the outcomes and incidence of liver transplantation performed at the University of São Paulo and to compare those with the State of São Paulo before and after adoption of the Model for End-Stage Liver Disease (MELD) score. Method Evaluation of the number of liver transplantations before and after adoption of the MELD score. Mean values and standard deviations were used to analyze normally distributed variables. The incidence results were compared with those of the State of São Paulo. Results There was a high prevalence of male patients, with a predominance of middle-aged. The main indication for liver transplantation was hepatitis C cirrhosis. The mean and median survival rates and overall survival over ten and five years were similar between the groups (p>0.05). The MELD score increased over the course of the study period for patients who underwent liver transplantation (p>0.05). There were an increased number of liver transplants after adoption of the MELD score at this institution and in the State of São Paulo (p<0.001). Conclusion The adoption of the MELD score led to increase the number of liver transplants performed in São Paulo.

Abdominal wall hernia in cirrhotic patients: emergency surgery results in higher morbidity and mortality

BackgroundPatients with cirrhosis have a high incidence of abdominal wall hernias and carry an elevated perioperative morbidity and mortality. The optimal surgical management strategy as well as timing of abdominal hernia repair remains controversial.MethodsA cohort study of 67 cirrhotic patients who underwent hernia repair during the period of January 1998-December 2009 at the University Hospital of Sao Paulo were included. After meeting study criteria, a total of 56 patients who underwent 61 surgeries were included in the final analysis. Patient characteristics, morbidity (Clavien score), mortality, Child-Turcotte-Pugh score, MELD score, use of prosthetic material, and elective or emergency surgery have been analysed with regards to morbidity and 30-day mortality.ResultsThe median MELD score of the patient population was 14 (range: 6 to 24). Emergency surgery was performed in 34 patients because of ruptured hernia (n = 13), incarceration (n = 10), strangulation (n = 4), and skin necrosis or ulceration (n = 7). Elective surgery was performed in 27 cases. After a multivariable analysis, emergency surgery (OR 7.31; p 0.017) and Child-Pugh C (OR 4.54; p 0.037) were risk factors for major complications. Moreover, emergency surgery was a unique independent risk factor for 30-day mortality (OR 10.83; p 0.028).ConclusionsHigher morbidity and mortality are associated with emergency surgery in advanced cirrhotic patients. Therefore, using cirrhosis as a contraindication for hernia repair in all patients may be reconsidered in the future, especially after controlling ascites and in those patients with hernias that are becoming symptomatic or show signs of possible skin necrosis and rupture. Future prospective randomized studies are needed to confirm this surgical strategy.

LATE ACUTE REJECTION IN LIVER TRANSPLANT: A SYSTEMATIC REVIEW

Introduction: Late acute rejection leads to worse patient and graft survival after liver transplantation. Aim: To analyze the reported results published in recent years by leading transplant centers in evaluating late acute rejection and update the clinical manifestations, diagnosis and treatment of liver transplantation. Method: Systematic literature review through Medline-PubMed database with headings related to late acute rejection in articles published until November 2013 was done. Were analyzed demographics, immunosuppression, rejection, infection and graft and patient survival rates. Results: Late acute rejection in liver transplantation showed poor results mainly regarding patient and graft survival. Almost all of these cohort studies were retrospective and descriptive. The incidence of late acute rejection varied from 7-40% in these studies. Late acute rejection was one cause for graft loss and resulted in different outcomes with worse patient and graft survival after liver transplant. Late acute rejection has been variably defined and may be a cause of chronic rejection with worse prognosis. Late acute rejection occurs during a period in which the goal is to maintain lower immunosuppression after liver transplantation. Conclusion: The current articles show the importance of late acute rejection. The real benefit is based on early diagnosis and adequate treatment at the onset until late follow up after liver transplantation.

Laparoscopy in Liver Transplantation: The Future Has Arrived

In the last two decades, laparoscopy has revolutionized the field of surgery. Many procedures previously performed with an open access are now routinely carried out with the laparoscopic approach. Several advantages are associated with laparoscopic surgery compared to open procedures: reduced pain due to smaller incisions and hemorrhaging, shorter hospital length of stay, and a lower incidence of wound infections. Liver transplantation (LT) brought a radical change in life expectancy of patients with hepatic end-stage disease. Today, LT represents the standard of care for more than fifty hepatic pathologies, with excellent results in terms of survival. Surely, with laparoscopy and LT being one of the most continuously evolving challenges in medicine, their recent combination has represented an astonishing scientific progress. The intent of the present paper is to underline the current role of diagnostic and therapeutic laparoscopy in patients waiting for LT, in the living donor LT and in LT recipients.

Prognostic implication of mucinous histology in resected colorectal cancer liver metastases.

BACKGROUND Colorectal mucinous adenocarcinoma (MAC) is a subtype of colorectal adenocarcinoma with prominent mucin production associated with proximal location of tumor, advanced stage at diagnosis, microsatellite instability, and BRAF mutation. The prognostic implication of MAC in colorectal cancer liver metastases (CRCLM) is unknown. The purpose of our study was to determine the frequency and elucidate the prognostic implication of mucinous histology in CRCLM. METHODS The medical records of 118 patients who underwent CRCLM resection between 2000 and 2010 were reviewed. Clinicopathologic variables and outcome parameters were examined. Resected specimens were submitted to routine histologic evaluation. Patients were grouped according to the metastasis mucinous content: >50%, MAC; <50%, adenocarcinoma with intermediated mucinous component (AIM); and without any mucinous component, non-MAC (NMA). RESULTS Mean follow-up after resection was 37 months. Tumor recurrence was observed in 75% of patients. Overall survival and disease-free survival rates after hepatectomy were 61%, 56%, and 26%, 24% at 3 and 5 years, respectively. Tumors with mucinous component (AIM and MAC) were related to proximal location of the primary tumor and were more frequently observed in females. Multivariate analysis revealed that MAC was an independent negative prognostic factor (hazard ratio, 3.13; 95% CI, 1.30-6.68; P = .011) compared with non-MAC (NMA and AIM). CONCLUSION MAC has an adverse prognostic impact compared with NMA, which may influence therapeutic strategy raising an important subject for discussion and future investigation.

The hepatopulmonary syndrome

Hepatopulmonary Syndrome is an uncommon clinical situation of unknown cause. It remains the focus of intense investigation and ongoing debate. The authors present a case of a 77 year old man with chronic liver disease known for 5 years, who developed central cyanoses, digital clubbing and hypoxemia. On searching for the cause of these clinical features, the diagnosis of Hepatopulmonary Syndrome was admitted and confirmed by contrast enhanced echocardiography using agitated saline, and also by technetium 99m-labelled macroaggregated albumin scanning.