Liver transplantation for hepatocellular carcinoma: results of a multicenter study with common priorization criteria.

OBJECTIVE: To evaluate the results of liver transplantation (OLT) performed for hepatocellular carcinoma (HCC) among a multicenter cohort of patients with predefined common inclusion and priorization criteria. PATIENTS AND METHODS: Over a 5-year period (January 2002-December 2006), 199 HCC patients underwent OLT in four centers in Andalusia. The morphological (Milan) inclusion criteria were priorized in two consecutive periods, according to the Model for End-stage Liver Disease score: group I, 53 patients (HCC < 2 cm = 24 points; > or = 2 cm or multinodular = 29 points) and group II, 146 cases (HCC < 3 cm without priorization; HCC > or = 3 cm or multinodular = 18 points). RESULTS: Among the 199 HCCs, 186 (93.5%) subjects were transplanted and 13 (6.5%) were excluded. There were 18 cases (9.7%) where the diagnosis was incidental and 168 were known HCC cases; 144 (85.7%) complied with the Milan criteria (Milan+); 24 (14.3%) exceeded there criteria (Milan-). According to preoperative imaging, the number of nodules and tumor mean sizes among the excluded-Milan+ and Milan- groups-were 1.8/5.3 cm, 1.4/3.5 cm, and 2.3/6.7 cm, respectively (P < .001). Percutaneous treatment during listing was delivered to 55% of the excluded cases: 49% of Milan+ and 96% of Milan-. The median time on the list was 88 days for known HCC (53 days for group I, and 97 days for group II), and 172 days for the incidental HCCs. Staging (pTNM) was correct in 64% of cases: 23% were understaged and 13% were overstaged. Overall mortality within the first 90 days was 9%, and transplant patient survival at 5 years was 61%. No differences were observed in survival rates between both study periods, although there were differences between the Milan+ (65%) and Milan- (23%) groups (P < .04). In addition, the difference in the recurrence rates was also significant between the Milan+ (7%), Milan- (24%), and the incidental (25%) groups (P < .02). CONCLUSIONS: A common priorization policy of HCC for OLT based on morphological criteria results in a low exclusion rate on the waiting lists (6.5%). The Milan criteria are still a good cutoff to stratify the risk of recurrence, despite preoperative tumor staging being correct in only two-thirds of cases.

Gallbladder tuberculosis: false-positive PET diagnosis of gallbladder cancer.

Gallbladder tuberculosis (GT) is an extremely rare disease, and very few cases have been reported in the literature. The first case of GT was described in 1870 by Gaucher. A correct preoperative diagnosis of GT is unusual, and it is frequently confused with various gallbladder diseases. We present a new case of a patient who underwent surgery with the preoperative diagnosis of gallbladder cancer after a false positive positron emission tomography scan in the diagnostic work-up.

Early postoperative response of cytokines in liver transplant recipients.

We evaluated the early postoperative response of several cytokines (IL-2, IL-4, IL-6, IL-10, TNF-alpha, IFN-gamma) prior to liver transplantation (T(0)) as well as 1, 6, and 12 hours and 1, 2, 3, 5, and 7 days afterward. Cytokine concentrations were correlated with serum levels of bilirubin as a predictor of postoperative complications. Cytokine levels were determined in plasma samples from 16 liver transplant recipients (13 men, 3 women) aged 43 to 61 years. IL-6 and IL-10 reached their maximum concentrations 1 hour after transplantation. Each increase in IL-6 correlated to a rise in IL-10. IL-2, IL-4, TNF-alpha, and IFN-gamma had a particular time-course for each patient studied. Bilirubin fell to almost normal values but not in cases of postoperative complications, where IL-6 showed values four times higher compared to those of liver transplant recipients who did not show postoperative complications. IL-6 and IL-10 plasma concentrations and serum bilirubin level might be useful as a predictive factor of postoperative complications in liver transplant recipients.

Time course of intraoperative cytokine levels in liver transplant recipients.

We evaluated the levels of several cytokines (interleukin [IL]-2, IL-4, IL-6, IL-10, tumor necrosis factor [TNF]-alpha, and interferon [IFN]-gamma) in plasma samples obtained before surgical intervention (T0) and during intraoperative liver transplantation: after induction of anesthesia (I-1), 15 minutes of anhepatic phase (I-2), 5 minutes before reperfusion (I-3), 10 minutes after reperfusion (I-4), 20 minutes after reperfusion (I-5), 60 minutes after reperfusion (I-6), and 1 hour after liver transplantation (I-7). Cytokine levels were determined using a technique which combines ELISA technique and flow cytometry. The study was approved by the local clinical research (ethics) committee. Written informed consent was obtained from patients' relatives. Twenty patients (14 men, 6 women) aged 23 to 61 years, recipients of a liver transplantation were studied. The cytokine IL-2 plasma values were maintained during the whole study period, with a slight increase at 15 minutes of anhepatic phase (I-2). IL-4 showed a peak value 20 minutes after reperfusion (I-5). IL-6 increased its plasma value starting at 15 minutes of anhepatic phase (I-2), maintaining high concentrations during the whole intraoperative period. IL-10 increased progressively, reaching a maximum 1 hour after transplantation (I-7). TNF-alpha reached maximum plasma levels 20 minutes after reperfusion (I-5), whereas IFN-gamma showed a peak at 15 minutes of anhepatic phase (I-2). Our results indicate that the anhepatic phase (I-2) is the earliest phase during which proinflammatory and anti-inflammatory cytokines, such as IL-6 and IL-10, respectively, are involved during liver transplantation. We conclude that IL-6 is the first cytokine involved in the inflammatory response during liver transplantation.

Indications and therapeutical options in hepatolithiasis.

OBJECTIVE: to present our experience with the treatment of hepatolithiasis. EXPERIMENTAL DESIGN: a retrospective study. Every patient operated on during 2002-2004. RESULTS: mean age was 68.2 years. All patients were male. Two patients had been operated on before. The other three suffered from: monolobar Caroli s disease (1), cholangiocarcinoma (1), and hepatolihtiasis without clear etiologic factors (1). All of them had intrahepatic and extrahepatic litihiasis. Clinical signs included: pain in RUQ, fever, and jaundice. Bilirubin was 3.5 mg/dl (min: 1.7, max: 5.9), GGT: 676.2 IU/l (min: 29, max: 2039), and alkaline phosphatase: 400 IU/l (min: 100, max: 1136). Abdominal ultrasounds always correctly diagnosed HL. CT (3 patients) only diagnosed one case. ERCP (3 patients) and cholangio-MRI (2 patients) always diagnosed HL correctly. Surgical procedures were: hepatojejunostomy with lavage of bile duct (2 cases) and hepatectomy (3 cases) -both right (1) and left (2). We always performed an intraoperative ultrasonography and choledoscopy. Morbidity was: biliary fistula (1 case) treated by percutaneous drainage. No mortality occurred. Median stay was 8.8 days. Mean follow-up is 12 months (min: 11, max: 20). No relapse has been observed. CONCLUSIONS: HL is infrequent in Spain. Surgical treatment, usually liver resection, obtains good results with low morbidity and mortality.

Time course of antioxidant enzyme activities in liver transplant recipients.

Reactive oxygen species (ROS) play a central role in ischemia-reperfusion injury after organ transplantation. They are degraded by endogenous radical scavengers such as antioxidant enzymes. The purpose of this study was to evaluate the temporal variations of antioxidant enzyme activities in liver transplant recipients. The study was performed in 13 liver transplant patients (11 men and 2 women). Blood samples were obtained pre- and postsurgical intervention: before transplant (T(0)), and 1, 6, 12, 24, 48, and 72 hours, as well as 5 and 7 days thereafter. We determined total and specific superoxide dismutase (SOD) activity, catalase (CAT), glutathione peroxidase (GPX), and glutathione reductase (GR) activities as well as malondialdehyde (MDA) and low-density lipoproteins (LDL). The results showed increased SOD and mainly GPX activities after liver transplantation, which correlated with MDA levels. Total SOD activity was mainly represented by Mn-SOD (75%) and Cu,Zn-SOD (25%), whereas Fe-SOD was not detected. In conclusion, the enhanced antioxidant enzyme activities reported in this study indicated a control of oxidative stress generated in liver transplantation. In this sense, although MDA levels showed an enormeous increase at 1 hour after transplantation, the lipid peroxidation was compensated for by GPX activity.

Postlaparoscopic cholecystectomy bile leak secondary to an accessory duct of Luschka.

Complications produced by the sectioning of a nonvisualized duct of Luschka are uncommon during laparoscopic cholecystectomy. From 1999 through 2003, we performed 1351 laparoscopic cholecystectomies in our department and observed 2 cases (0.15%) of bile leakage due to duct of Luschka injury. Injury during laparoscopic cholecystectomy is usually produced by an excessively deep plane of dissection and by the anatomical localization of this accessory duct. Clinical symptoms are scarce after duct of Luschka injury. Numerous diagnostic methods have been used to detect these injuries. Nevertheless, careful clinical examination is still of the utmost importance. Noninvasive treatments are usually effective. In patients who present with acute abdomen, as in our cases, or who are not cured by noninvasive treatments, exploratory laparotomy is the best approach. The surgical treatment consists of a lavage of the abdominal cavity, closure of the duct of Luschka, and intraoperative cholangiography to confirm that the biliary tree is intact.

Role of Transarterial Chemoembolization to Downstage Hepatocellular Carcinoma Within the Milan Criteria.

The practice of treating candidates for liver transplantation (LT) for hepatocellular carcinoma (HCC), with locoregional therapies, is common in most transplantation centers. We present our results using transarterial chemoembolization (TACE) as a neo-adjuvant treatment in our center between 2002 and 2013 to determine its effectiveness in downstaging (DS) HCC within the Milan criteria (MC). Clinical variables were recorded of both donors and recipients, such as diagnosis and treatment, variables related to its etiology, the use of TACE as a neo-adjuvant treatment, immunosuppressive therapy, toxicity, recurrence of disease, exitus, and others. Sixty-four patients were analyzed. Median age was 57 (range, 51-64) years. In this study, 84% (54) were male and 16% (10) were women. Etiology of HCC was viral in 47% (30), alcoholic in 25% (16), and other in 28% (18). TACE was conducted in 45 patients (70%). Every patient included in our study presented a T2 stage (of tumor-nodes-metastasis [TNM]) before surgery, thus within the MC. However, DS protocol was performed in 5 patients (7.8%). We performed a bivariate analysis, having assessed that the use of TACE decreases T2 stage into T1-T0 stage (P < .05). We have also calculated the recurrence-free survival, which reaches up to 80% to 125 months. Furthermore, even though the statistical differences are not consistent due to the simple size presented, we conclude that TACE is a safe and effective therapy to control HCC progression during the waiting list time.

Complications Associated With Liver Transplantation in Recipients With Body Mass Index >35 kg/m(2): Would It Be a Poor Prognosis Predictive Factor?

BACKGROUND: Obesity is a global epidemic that continues to increase in a great number of countries, and it has become a major public health problem in Spain. Unfortunately, the impact of obesity on survival in liver transplantation (LT) recipients is underestimated and controversial. The aim of this study was to determine if obesity is a risk factor for morbidity and mortality after LT. METHODS: In a retrospective cohort study of the records of 180 consecutive patients who had undergone to LT from 2007 to 2013, 11 obese patients with body mass index (BMI) >35 kg/m(2) were identified. Their data have been compared with recipients with BMI 20-25 kg/m(2). RESULTS: There were no differences in demographic data, Child-Pugh score, Model for End-Stage Liver Disease score, or cause of liver failure. BMI >35 kg/m(2) recipients had a significantly higher rate of portal vein thrombosis before LT, compared with the BMI 20-25 kg/m(2) group (36.5% vs 13.9%; P = .041). There were also no differences in development of post-reperfusion syndrome. The groups were also comparable concerning morbidity rate after LT, stay in the intensive care unit, and global hospital stay. However, the mortality rate was significantly higher in the obese group compared with the nonobese group (72.7% vs 38.9%; P = .032). CONCLUSIONS: The results of the study clearly demonstrate higher mortality rates in obese patients undergoing LT; thus, it is fair to consider obesity as a poor prognosis predictive factor concerning mortality rate.

Immunosuppression Strategies in the Treatment of Hepatocellular Carcinoma in Virgen de las Nieves University Hospital.

BACKGROUND: We describe an observational, retrospective study that included patients who underwent a liver transplantation (LT) for hepatocellular carcinoma (HCC) in our center between 2004 and 2012. METHODS: Clinical variables were recorded for donors and recipients as diagnosis and treatment, immunosuppressive therapy, toxicity, graft dysfunction, recurrence, and exitus. Fifty-eight patients were analyzed. The mean age was 57 ± 8 years. The viral etiology of HCC was 50% (n = 29), alcoholic 26% (n = 15), and others, 24% (n = 14). Regarding initial immunosuppressive strategy (IS), 51 patients (87.9%) were treated with standard regimen with corticosteroids (CS) and tacrolimus (TA), compared with 7 patients with impaired renal function (12.1%) who underwent a delayed therapy with calcineurin inhibitors (CNI) + mycophenolate mophetil (MMF) + CS. Concomitant use of anti-CD25 monoclonal antibodies was less than 10%. Regarding maintenance, 43 patients (74.1%) were treated with MMF + CNI versus 15 treated only with TA (25.9%). RESULTS: Recurrence of HCC was approximately 12%: 7 patients (2 hepatic only, 5 also extra-hepatic). Exitus was established in 19 patients (32.75%); only 3 patients (5.17%) were attributable to HCC. Bivariate studies were conducted according to the initial IS (standard regimen versus delayed therapy) and maintenance therapy (MMF + TA versus TA alone), with no differences in any of them in recurrence, treatment toxicity, graft rejection, and dysfunction. CONCLUSIONS: In our experience with the IS, we found no differences in the development of recurrent disease, treatment toxicity, development of graft dysfunction, or rejection. We believe that individualized immunosuppressive therapy in these patients is safe and effective.

Retroperitoneal actinomycosis due to dropped gallstones.

Dropped bile and gallstones after accidental perforation of the biliary gallbladder is a frequent event during laparoscopic cholecystectomy and is generally of no clinical importance. However, calculi left in the abdominal cavity can produce a series of severe late complications. We present a patient with retroperitoneal actinomycosis produced by dropped gallstones after a laparoscopic cholecystectomy.

Experience of the transplant unit from Virgen de las Nieves Hospital in using liver grafts from asystolic donors.

Given the shortage of donors, it has become increasingly necessary to use alternative sources to meet the growing demand for organs, and evolution in the use of asystolic donors is proving to be an important resource in helping to meet those needs. The goal of this study is to describe the initial results of our experience with Type II asystolic donation. An observational retrospective study was conducted to analyze the variables of four cases in this type of donation. After the analysis we conclude that, despite the limited number of cases in our series, the results are compatible with larger series and permit us to continue to value this method as a resource for broadening the donor pool.

Liver transplantation using low-weight recipients from a graft split program.

We present our experience with a split liver (SL) program shared with the children's liver transplantation (LT) program from 2 different hospitals in the use of partial grafts from cadaver donors in brain death. We describe an observational, retrospective study, which included patients who underwent a SL transplantation in our center between January 2006 and December 2012. Clinical variables were recorded of both donors and recipients and their data were analyzed using SPSS 19.0 software. Of a total of 204 LT, 4 (2%) patients were treated with a SL. The causes of LT were alcoholic cirrhosis in 2 cases, cryptogenic cirrhosis, and primary biliary cirrhosis (PBC). In all cases there was a temporary portocaval shunt. The confluence of the hepatic veins of the recipient was anastomosed to the donor vena cava and arterial anastomosis was performed. The reconstruction was hepato-choledochal in all cases. There were no cases of postreperfusion syndrome or vascular thrombosis and no retransplantation was necessary. Currently, 3 of the 4 cases are still alive. Death in the other patient was due to mesenteric ischemia. Our center has participated in the development of a protocol that considers the indication of this technique provided expert groups are involved in its development, regardless of hospital level. This will expand the pool of donors and partially solve the current problems with available grafting.

Indicaciones y opciones terapéuticas en la hepatolitiasis / Indications and therapeutical options in hepatolithiasis

Objetivo: presentar nuestra experiencia en el tratamiento dela hepatolitiasis (HL).Pacientes y métodos: diseño experimental: estudio retrospectivode casos. Se han incluido todos los pacientes intervenidosde hepatolitiasis entre 2002 a 2004.Resultados: la edad media fue 68,2 años, todos ellos varones.Dos pacientes habían sido intervenidos previamente. Losotros tres presentaban: enfermedad de Caroli monolobar (1), colangiocarcinoma(1) y hepatolitiasis sin factores etiológicos asociados.Todos los pacientes presentaban litiasis de localización intrahepáticay extrahepática. La clínica habitual fue: dolor enhipocondrio derecho, fiebre e ictericia. La bilirribuna media fue:3,5 mg/dl (mínimo: 1,7, máximo: 5,9), GGT: 676,2 UI/l (mínimo:29, máximo: 2039), y fosfatasa alcalina: 400 UI/l (mínimo:100, máximo: 1136). La ecografía detectó siempre la HL. Se realizóTAC en 3 pacientes, que sólo observó la HL en uno. LaCPRE, realizada en 3 pacientes, diagnosticó correctamente la HL.La colangioRMN, efectuada en dos ocasiones, fue siempre diagnóstica.Las intervenciones fueron: hepaticoyeyunostomía y lavadode la vía biliar (2 pacientes) y hepatectomía (3 casos): derecha(1) e izquierda (2). Se practicó siempre ecografía y coledoscopiaintraoperatoria. La morbilidad fue: fístula biliar tratada mediantedrenaje percutáneo. No se produjo mortalidad. La estancia mediafue 8,8 días. El seguimiento medio es de 12 meses (mínimo: 11,máximo: 20) y no hemos observado recidiva de HL.Conclusiones: la HL es infrecuente en España. El tratamientoquirúrgico, frecuentemente hepatectomía, obtiene buenos resultadoscon baja morbimortalidad

Objective: to present our experience with the treatment ofhepatolithiasis.Patients and methods: experimental design: a retrospectivestudy. Every patient operated on during 2002-2004.Results: mean age was 68.2 years. All patients were male.Two patients had been operated on before. The other three sufferedfrom: monolobar Caroli's disease (1), cholangiocarcinoma(1), and hepatolihtiasis without clear etiologic factors (1). All ofthem had intrahepatic and extrahepatic litihiasis. Clinical signs included:pain in RUQ, fever, and jaundice. Bilirubin was 3.5 mg/dl(min: 1.7, max: 5.9), GGT: 676.2 IU/l (min: 29, max: 2039),and alkaline phosphatase: 400 IU/l (min: 100, max: 1136). Abdominalultrasounds always correctly diagnosed HL. CT (3 patients)only diagnosed one case. ERCP (3 patients) and cholangio-MRI (2 patients) always diagnosed HL correctly. Surgicalprocedures were: hepatojejunostomy with lavage of bile duct (2cases) and hepatectomy (3 cases) –both right (1) and left (2). Wealways performed an intraoperative ultrasonography and choledoscopy.Morbidity was: biliary fistula (1 case) treated by percutaneousdrainage. No mortality occurred. Median stay was 8.8 days.Mean follow-up is 12 months (min: 11, max: 20). No relapse hasbeen observed.Conclusions: HL is infrequent in Spain. Surgical treatment,usually liver resection, obtains good results with low morbidity andmortality

Tumor mesenquimal de vesícula biliar / Gastrointestinal stromal tumor of the gallbladder

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