Luciana Bertocco de Paiva Haddad

Lymph Node Involvement and Not the Histophatologic Subtype Is Correlated with Outcome After Resection of Adenocarcinoma of the Ampulla of Vater

BackgroundIntestinal and pancreaticobiliary types of Vater’s ampulla adenocarcinoma have been considered as having different biologic behavior and prognosis. The aim of the present study was to determine the best immunohistochemical panel for tumor classification and to analyze the survival of patients having these histological types of adenocarcinoma.MethodNinety-seven resected ampullary adenocarcinomas were histologically classified, and the prognosis factors were analyzed. The expression of MUC1, MUC2, MUC5AC, MUC6, CK7, CK17, CK20, CD10, and CDX2 was evaluated by using immunohistochemistry.ResultsForty-three Vater’s ampulla carcinomas were histologically classified as intestinal type, 47 as pancreaticobiliary, and seven as other types. The intestinal type had a significantly higher expression of MUC2 (74.4% vs. 23.4%), CK20 (76.7% vs. 29.8%), CDX2 (86% vs. 21.3%), and CD10 (81.4% vs. 51.1%), while MUC1 (53.5% vs. 82.9%) and CK7 (79.1% vs. 95.7%) were higher in pancreatobiliary adenocarcinomas. The most accurate markers for immunohistochemical classification were CDX2, MUC1, and MUC2. Survival was significantly affected by pancreaticobiliary type (p = 0.021), but only lymph node metastasis, lymphatic invasion, and stage were independent risk factors for survival in a multivariate analysis.ConclusionThe immunohistochemical expression of CDX2, MUC1, and MUC2 allows a reproducible classification of ampullary carcinomas. Although carcinomas of the intestinal type showed better survival in the univariate analysis, neither histological classification nor immunohistochemistry were independent predictors of poor prognosis.

Pancreatic fistula after pancreaticoduodenectomy: the conservative treatment of choice

BACKGROUND A pancreatic fistula (PF) is the most common complication after pancreaticoduodenectomy (PD), and its reported incidence varies from 2% to 28%. The aim of the present study was to analyse the treatment of a complicated PF comparing the surgical approach with conservative techniques. METHODS From January 2000 through to August 2006, 121 patients were submitted for PD. The study consisted of 70 men and 47 women, with a median age of 60 years (SD +/- 12). The main indications for PD were pancreatic duct carcinoma in 52 patients (44.5%), ampullary carcinoma or adenoma in 18 (15.4%) and islet cell tumour in 11 (9.4%). Reconstruction by pancreatogastrostomy was performed in 65 patients (55.6%), and pancreatojejunostomy in 52 patients (44%). RESULTS Thirty-five patients (30%) developed a PF. Amongst these, 20 were managed conservatively and 14 were reoperated. These two groups of patients were compared with patients without a PF for analysis. There was no significant difference in the mean age, the gender ratio, American Society of Anesthesiologists (ASA) classification, surgical time and blood replacement, number of associated procedures, vascular resection and type of reconstruction between the three groups. There were five post-operative deaths (4.2%), three patients (21.4%) in the surgical treatment group (P < 0.01). Mean total number of complications (P= 0.02) and mean length of hospital stay (P < 0.001) were greater in the surgical group. The medium delay between the pancreatic resection and reoperation was 10 days (range, 3-32 days). Completion splenopancreatectomy was required in five patients whereas conservative treatment including debridement and drainage was applied in nine patients. CONCLUSION The surgical approach for a PF is associated with a higher mortality and morbidity. There is no advantage in performing completion pancreatectomy (CP) instead of extensive drainage as a result of the same mortality and morbidity rates and the risk of endocrine insufficiency. In cases of complicated PF, radiological or surgical conservative treatment is recommended.

Lessons Learned from the First 100 Laparoscopic Liver Resections: Not Delaying Conversion May Allow Reduced Blood Loss and Operative Time

BACKGROUND The laparoscopic approach to liver resective surgery is slowly spreading to specialized centers. Little is known about factors influencing the immediate postoperative outcome. STUDY DESIGN The purpose of the study was to evaluate the immediate outcome of laparoscopic liver resection (LLR), with particular emphasis on intraoperative bleeding and conversion. A retrospective analysis of demographic, clinical, and surgical data, including conversion, morbidity/mortality, and hospital stay, of the first 100 patients at our institution undergoing LLR from February 1997 through March 2007 was performed. RESULTS Indication for LLR was benign lesion in 28 patients, malignancy in 33, and living donation in 39. Seventy-five resections involved two or more segments. Mean blood loss was 120 ± 127.6 mL. One patient (1%) required transfusion. Mean operative time was 253 ± 91.6 minutes. No patient died. Postoperative complications occurred in 21 patients. The conversion rate was 17%. Variables related to conversion were American Society of Anesthesiologists Class II, body mass index, cirrhosis, necessity for the Pringle maneuver, and intraoperative blood loss. Conversion did not influence the operative time. Patients with conversion had more complications and a longer hospital stay. CONCLUSIONS Liver resection by laparoscopy is feasible and safe, implying low intraoperative blood loss. Not perfect physical conditions, cirrhosis, high body mass index, and, intraoperatively, blood loss and the necessity of a Pringle maneuver should be considered risk factors for conversion. A meticulous dissection by bipolar coagulation, Harmonic(®) (Ethicon) scalpel, and ultrasound dissector, other than the attitude not to delay conversion in difficult cases, may allow for low blood loss without prolongation of operative time, with a possible, slight increase of the conversion rate.

Factors Associated with Mortality and Graft Failure in Liver Transplants: A Hierarchical Approach

Background Liver transplantation has received increased attention in the medical field since the 1980s following the introduction of new immunosuppressants and improved surgical techniques. Currently, transplantation is the treatment of choice for patients with end-stage liver disease, and it has been expanded for other indications. Liver transplantation outcomes depend on donor factors, operating conditions, and the disease stage of the recipient. A retrospective cohort was studied to identify mortality and graft failure rates and their associated factors. All adult liver transplants performed in the state of São Paulo, Brazil, between 2006 and 2012 were studied. Methods and Findings A hierarchical Poisson multiple regression model was used to analyze factors related to mortality and graft failure in liver transplants. A total of 2,666 patients, 18 years or older, (1,482 males; 1,184 females) were investigated. Outcome variables included mortality and graft failure rates, which were grouped into a single binary variable called negative outcome rate. Additionally, donor clinical, laboratory, intensive care, and organ characteristics and recipient clinical data were analyzed. The mortality rate was 16.2 per 100 person-years (py) (95% CI: 15.1–17.3), and the graft failure rate was 1.8 per 100 py (95% CI: 1.5–2.2). Thus, the negative outcome rate was 18.0 per 100 py (95% CI: 16.9–19.2). The best risk model demonstrated that recipient creatinine ≥ 2.11 mg/dl [RR = 1.80 (95% CI: 1.56–2.08)], total bilirubin ≥ 2.11 mg/dl [RR = 1.48 (95% CI: 1.27–1.72)], Na+ ≥ 141.01 mg/dl [RR = 1.70 (95% CI: 1.47–1.97)], RNI ≥ 2.71 [RR = 1.64 (95% CI: 1.41–1.90)], body surface ≥ 1.98 [RR = 0.81 (95% CI: 0.68–0.97)] and donor age ≥ 54 years [RR = 1.28 (95% CI: 1.11–1.48)], male gender [RR = 1.19(95% CI: 1.03–1.37)], dobutamine use [RR = 0.54 (95% CI: 0.36–0.82)] and intubation ≥ 6 days [RR = 1.16 (95% CI: 1.10–1.34)] affected the negative outcome rate. Conclusions The current study confirms that both donor and recipient characteristics must be considered in post-transplant outcomes and prognostic scores. Our data demonstrated that recipient characteristics have a greater impact on post-transplant outcomes than donor characteristics. This new concept makes liver transplant teams to rethink about the limits in a MELD allocation system, with many teams competing with each other. The results suggest that although we have some concerns about the donors features, the recipient factors were heaviest predictors for bad outcomes.

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.

Does autologous blood transfusion during liver transplantation for hepatocellular carcinoma increase risk of recurrence

AIM To analyze outcomes in patients who underwent liver transplantation (LT) for hepatocellular carcinoma (HCC) and received autologous intraoperative blood salvage (IBS). METHODS Consecutive HCC patients who underwent LT were studied retrospectively and analyzed according to the use of IBS or not. Demographic and surgical data were collected from a departmental prospective maintained database. Statistical analyses were performed using the Fishers exact test and the Wilcoxon rank sum test to examine covariate differences between patients who underwent IBS and those who did not. Univariate and multivariate Cox regression models were developed to evaluate recurrence and death, and survival probabilities were estimated using the Kaplan-Meier method and compared by the log-rank test. RESULTS Between 2002 and 2012, 158 consecutive patients who underwent LT in the same medical center and by the same surgical team were identified. Among these patients, 122 (77.2%) were in the IBS group and 36 (22.8%) in the non-IBS group. The overall survival (OS) and recurrence free survival (RFS) at 5 years were 59.7% and 83.3%, respectively. No differences in OS (P = 0.51) or RFS (P = 0.953) were detected between the IBS and non-IBS groups. On multivariate analysis for OS, degree of tumor differentiation remained as the only independent predictor. Regarding patients who received IBS, no differences were detected in OS or RFS (P = 0.055 and P = 0.512, respectively) according to the volume infused, even when outcomes at 90 d or longer were analyzed separately (P = 0.518 for both outcomes). CONCLUSION No differences in RFS or OS were detected according to IBS use. Trials addressing this question are justified and should be designed to detect small differences in long-term outcomes.

S-Nitroso-N-Acetylcysteine Ameliorates Ischemia-Reperfusion Injury In The Steatotic Liver

BACKGROUND: Steatosis is currently the most common chronic liver disease and it can aggravate ischemia-reperfusion (IR) lesions. We hypothesized that S-nitroso-N-acetylcysteine (SNAC), an NO donor component, can ameliorate cell damage from IR injury. In this paper, we report the effect of SNAC on liver IR in rats with normal livers compared to those with steatotic livers. METHODS: Thirty-four rats were divided into five groups: I (n=8), IR in normal liver; II (n=8), IR in normal liver with SNAC; III (n=9), IR in steatotic liver; IV (n=9), IR in steatotic liver with SNAC; and V (n=10), SHAN. Liver steatosis was achieved by administration of a protein-free diet. A SNAC solution was infused intraperitoneally for one hour, beginning 30 min. after partial (70%) liver ischemia. The volume of solution infused was 1 ml/100 g body weight. The animals were sacrificed four hours after reperfusion, and the liver and lung were removed for analysis. We assessed hepatic histology, mitochondrial respiration, oxidative stress (MDA), and pulmonary myeloperoxidase. RESULTS: All groups showed significant alterations compared with the group that received SHAN. The results from the steatotic SNAC group revealed a significant improvement in liver mitochondrial respiration and oxidative stress compared to the steatotic group without SNAC. No difference in myeloperoxidase was observed. Histological analysis revealed no difference between the non-steatotic groups. However, the SNAC groups showed less intraparenchymal hemorrhage than groups without SNAC (p=0.02). CONCLUSION: This study suggests that SNAC effectively protects against IR injury in the steatotic liver but not in the normal liver.

Utilization of the lower inflection point of the pressure-volume curve results in protective conventional ventilation comparable to high frequency oscillatory ventilation in an animal model of acute respiratory distress syndrome.

INTRODUCTION Studies comparing high frequency oscillatory and conventional ventilation in acute respiratory distress syndrome have used low values of positive end-expiratory pressure and identified a need for better recruitment and pulmonary stability with high frequency. OBJECTIVE To compare conventional and high frequency ventilation using the lower inflection point of the pressure-volume curve as the determinant of positive end-expiratory pressure to obtain similar levels of recruitment and alveolar stability. METHODS After lung lavage of adult rabbits and lower inflection point determination, two groups were randomized: conventional (positive end-expiratory pressure = lower inflection point; tidal volume=6 ml/kg) and high frequency ventilation (mean airway pressures= lower inflection point +4 cmH2O). Blood gas and hemodynamic data were recorded over 4 h. After sacrifice, protein analysis from lung lavage and histologic evaluation were performed. RESULTS The oxygenation parameters, protein and histological data were similar, except for the fact that significantly more normal alveoli were observed upon protective ventilation. High frequency ventilation led to lower PaCO2 levels. DISCUSSION Determination of the lower inflection point of the pressure-volume curve is important for setting the minimum end expiratory pressure needed to keep the airways opened. This is useful when comparing different strategies to treat severe respiratory insufficiency, optimizing conventional ventilation, improving oxygenation and reducing lung injury. CONCLUSIONS Utilization of the lower inflection point of the pressure-volume curve in the ventilation strategies considered in this study resulted in comparable efficacy with regards to oxygenation and hemodynamics, a high PaCO2 level and a lower pH. In addition, a greater number of normal alveoli were found after protective conventional ventilation in an animal model of acute respiratory distress syndrome.

Uterine transplantation: a systematic review

Up to 15% of the reproductive population is infertile, and 3 to 5% of these cases are caused by uterine dysfunction. This abnormality generally leads women to consider surrogacy or adoption. Uterine transplantation, although still experimental, may be an option in these cases. This systematic review will outline the recommendations, surgical aspects, immunosuppressive drugs and reproductive aspects related to experimental uterine transplantation in women.

MELD Era Increases the Number of Combined Liver and Kidney Transplantations

Introduction: Combined Liver and Kidney Transplantation (CKLT) procedure is performed in large transplant centers worldwide as a therapeutic option for patients with disease in both organs and is currently the procedure of choice in many centers. The objective of this study was the evaluation of the number of combined transplantations before and after adoption of the MELD score in the Liver and Gastrointestinal Transplant Division of the University of Sao Paulo (Brazil) and comparison with the State of Sao Paulo. Method: Clinical data from 705 transplantations performed from January 2002 to July 2012 were studied. Overall patient survival was analyzed by the Kaplan-Meier method for patients who underwent either combined liver and kidney transplantation or liver transplantation alone. Evaluation of the number of combined transplantations before and after adoption of the MELD score. The mean values and standard deviations were used to examine normally distributed variables. Comparison the incidence results with the CLKT and LT on State of Sao Paulo. Results: There was a high prevalence of male patients referred to both modalities of transplantation. The mean age of patients was also similar in both groups, with a predominance of middle-aged males. The predominant reason for transplantation was hepatitis C cirrhosis (25.8%) in the CLKT group. The mean and median survival rates and survival over 10 years were similar between the groups (p= 0.620). The MELD score increases over the course of the period analyzed for patients who underwent both modalities of transplantation (p=0.46). There was an increase in the number of CLKTs after adoption of the MELD score in our institution and in State of Sao Paulo (p<0.001). Conclusion: The adoption of the MELD score increase the number of combined transplants performed. The survival rate for Combined Liver and Kidney Transplantation is similar to that of Liver Transplantation alone.