Juan Carlos García-Valdecasas

Laparoscopy-assisted colectomy versus open colectomy for treatment of non-metastatic colon cancer: a randomised trial

BACKGROUND Although early reports on laparoscopy-assisted colectomy (LAC) in patients with colon cancer suggested that it reduces perioperative morbidity, its influence on long-term results is unknown. Our study aimed to compare efficacy of LAC and open colectomy (OC) for treatment of non-metastatic colon cancer in terms of tumour recurrence and survival. METHODS From November, 1993, to July, 1998, all patients with adenocarcinoma of the colon were assessed for entry in this randomised trial. Adjuvant therapy and postoperative follow-up were the same in both groups. The main endpoint was cancer-related survival. Data were analysed according to the intention-to-treat principle. FINDINGS 219 patients took part in the study (111 LAC group, 108 OC group). Patients in the LAC group recovered faster than those in the OC group, with shorter peristalsis-detection (p=0.001) and oral-intake times (p=0.001), and shorter hospital stays (p=0.005). Morbidity was lower in the LAC group (p=0.001), although LAC did not influence perioperative mortality. Probability of cancer-related survival was higher in the LAC group (p=0.02). The Cox model showed that LAC was independently associated with reduced risk of tumour relapse (hazard ratio 0.39, 95% CI 0.19-0.82), death from any cause (0.48, 0.23-1.01), and death from a cancer-related cause (0.38, 0.16-0.91) compared with OC. This superiority of LAC was due to differences in patients with stage III tumours (p=0.04, p=0.02, and p=0.006, respectively). INTERPRETATION LAC is more effective than OC for treatment of colon cancer in terms of morbidity, hospital stay, tumour recurrence, and cancer-related survival.

Benefit of adjuvant chemotherapy for resectable gastric cancer: A meta-analysis

CONTEXT Despite potentially curative resection of stomach cancer, 50% to 90% of patients die of disease relapse. Numerous randomized clinical trials (RCTs) have compared surgery alone with adjuvant chemotherapy, but definitive evidence is lacking. OBJECTIVES To perform an individual patient-level meta-analysis of all RCTs to quantify the potential benefit of chemotherapy after complete resection over surgery alone in terms of overall survival and disease-free survival, and to further study the role of regimens, including monochemotherapy; combined chemotherapy with fluorouracil derivatives, mitomycin C, and other therapies but no anthracyclines; combined chemotherapy with fluorouracil derivatives, mitomycin C, and anthracyclines; and other treatments. DATA SOURCES Data from all RCTs comparing adjuvant chemotherapy with surgery alone in patients with resectable gastric cancer. We searched MEDLINE (up to 2009), the Cochrane Central Register of Controlled Trials, the National Institutes of Health trial registry, and published proceedings from major oncologic and gastrointestinal cancer meetings. STUDY SELECTION All RCTs closed to patient recruitment before 2004 were eligible. Trials testing radiotherapy; neoadjuvant, perioperative, or intraperitoneal chemotherapy; or immunotherapy were excluded. Thirty-one eligible trials (6390 patients) were identified. DATA EXTRACTION As of 2010, individual patient data were available from 17 trials (3838 patients representing 60% of the targeted data) with a median follow-up exceeding 7 years. RESULTS There were 1000 deaths among 1924 patients assigned to chemotherapy groups and 1067 deaths among 1857 patients assigned to surgery-only groups. Adjuvant chemotherapy was associated with a statistically significant benefit in terms of overall survival (hazard ratio [HR], 0.82; 95% confidence interval [CI], 0.76-0.90; P < .001) and disease-free survival (HR, 0.82; 95% CI, 0.75-0.90; P < .001). There was no significant heterogeneity for overall survival across RCTs (P = .52) or the 4 regimen groups (P = .13). Five-year overall survival increased from 49.6% to 55.3% with chemotherapy. CONCLUSION Among the RCTs included, postoperative adjuvant chemotherapy based on fluorouracil regimens was associated with reduced risk of death in gastric cancer compared with surgery alone.

Evolution of indications and results of liver transplantation in Europe. A report from the European Liver Transplant Registry (ELTR).

Royal Free Hospital, London, UKIntroductionBackground of the European Liver Transplant RegistrySince 1968 the European Liver Transplant Registry (ELTR) collectsprospectively the data of liver transplantation (LT) in 145 centersall over Europe. It represents more than 95% of the overallEuropean data compared to the published official figures [1]. Thiscollectionismadeprospectivelythroughastandardizedquestion-naire. The first part of the questionnaire includes items regardingdate andindicationfor LT,donor andrecipientdata, surgical tech-niqueofLT,andtheimmediatepostoperativeimmunosuppressiontherapy. The second part concerns graft and patient outcome, andimmunosuppressive regimen follow-up. Participation in the ELTRis voluntary and a standard computerized database is provided tocontributing centers with detailed instructions for the collectionof accurate and uniform information [2].Along with reports concerning LT for specific hepatic diseases[3–12],ELTRhasallowedthedevelopmentofriskmodelsforliver-transplantation mortality according to the characteristics of thedonor and recipient, and of the transplant procedure [13,14].Qualityofthedataisassessedroutinely.Aregularauditingpro-cessisconductedeachyeartoensurethereliabilityofthescientificanalysis of the data, a control of the good adequacy between ELTRquestionnaire and patient charts is performed by randomly con-ductedauditvisits.ResultsoftheseauditvisitshaveindicatedthatELTR data were reliable and the scientific results of ELTR can beconsidered credible and representative of LT in Europe [15–18].In addition, a control quality program has been developed inter-nally. The data are subjected to checks for completeness, consis-tency, and range. Comprehensive logical intra- and inter-updatesare performed. Moreover, the ELTR has established agreementswith the European Organ Sharing Organizations (OSO): UnitedKingdom Transplant Service Support Authority (UKTransplant),Spanish Organizacion Nacional de Transplantes (ONT), Scandina-vian Scanditransplant (SKT), Dutch Transplant Foundation (NTS),Eurotransplant (ET), French Agence de la Biomedecine (ABM) toexchangedatacollectedfromEuropeanCentersandtocrosscheckcommon data between OSO and ELTR.Patients and methodsWe have first considered all data since 1968 to show the evolu-tion of results of LT in Europe since its initial development. Therest of the analysis has been undertaken during two differentperiods: (a) from January 1988 to December 2009 (89,865 LT –80,347 patients), where the date from January 1988 was chosenJournal of Hepatology 2012 vol. 57

Short-term outcome analysis of a randomized study comparing laparoscopic vs open colectomy for colon cancer

The authors examined the impact of the laparoscopic approach on the early outcome of resected colon carcinomas. The role of laparoscopic techniques in the treatment of colon carcinomas is questionable. Previous studies have suggested technical feasibility of surgical resections of these cancers by laparoscopic means and have implied a benefit to laparoscopic technique for patients undergoing colorectal resections. A prospective, randomized study was conducted comparing laparoscopic assisted colectomy (LAC) open colectomy (OC) for colon cancer. We present the preliminary results in relation to the short-term outcome and judge the feasibility of the laparoscopic procedure to as a way of performing accurate oncologic resection and staging. Benefit has been demonstrated with LAC in this setting. Passing flatus, oral intake, and discharge from hospital occurred earlier in LAC- than OC-treated patients The mean operative time was significantly longer in the LAC group than in the OC group. The overall morbidity was significantly lower in the LAC group. No significant differences were observed between both groups in the number of lymph nodes removed or the pathological stage following the Astler-Coller modification of the Dukes classification. The laparoscopic approach improves the short-term outcome of segmental colectomies for colon cancer. However, the further follow-up of these patients will allow us to answer in the near future whether or not the LAC may influence the long-term outcome.

Bacterial translocation of enteric organisms in patients with cirrhosis

BACKGROUND/AIMS The aim of the study was to investigate the prevalence and associated risk factors for bacterial translocation in patients with cirrhosis, a mechanism involved in the pathogenesis of bacterial infections in experimental cirrhosis. METHODS Mesenteric lymph nodes were obtained for microbiological culture from 101 patients with cirrhosis and from 35 non-cirrhotic patients. RESULTS Enteric organisms were grown from mesenteric lymph nodes in 8.6% of non-cirrhotic patients. In the 79 cirrhotic patients without selective intestinal decontamination, the prevalence of bacterial translocation significantly increased according to the Child-Pugh classification: 3.4% in Child A, 8.1% in Child B and 30.8% in Child C patients (chi2 = 6.106, P < 0.05). However, translocation by Enterobacteriaceae, the organisms commonly responsible for spontaneous bacteremia and peritonitis in cirrhosis, was only observed in 25% of the cases. The prevalence of bacterial translocation in the 22 cirrhotic patients undergoing selective intestinal decontamination, all Child-Pugh class B and C, was 4.5%. The Child-Pugh score was the only independent predictive factor for bacterial translocation (odds ratio 2.22, P = 0.02). CONCLUSIONS Translocation of enteric organisms to mesenteric lymph nodes is increased in patients with advanced cirrhosis and is reduced to the level found in non-cirrhotic patients by selective intestinal decontamination.

Antiviral therapy of patients with decompensated cirrhosis to prevent recurrence of hepatitis C after liver transplantation

BACKGROUND/AIMS After liver transplantation (LT) infection of the graft with the hepatitis C virus (HCV) is almost universal and chronic hepatitis and cirrhosis develop in a significant proportion of patients. One of the possible strategies to prevent HCV infection recurrence is to eradicate HCV before LT. METHODS We evaluated the efficacy and safety of antiviral therapy to prevent HCV recurrence in 30 HCV-cirrhotic patients awaiting LT. At the time of inclusion 15 patients were Child-Pugh A and 15 Child-Pugh B/C. The infecting genotype was 1b in 25 patients. Treatment with interferon alpha-2b 3 MU/day and ribavirin 800 mg/day was initiated when the expected time for LT was less than 4 months and continued until LT. The median duration of treatment was 12 weeks. RESULTS Nine patients (30%) achieved a virological response and 21 did not respond to therapy. In nine (43%) of the 21 non-responders viral load decreased > or =2 log10 during treatment. A viral load decrease > or = 2 log10 at week 4 of treatment was the strongest predictor of virological response. All nine virological responders have already undergone LT; six patients remain free of infection after a median follow-up of 46 weeks and HCV infection recurred in three patients after LT. In one of these patients HCV-RNA was still detectable in the explanted liver. Side effects were frequent and dose reduction was necessary in 19 (63%) of the 30 patients; no patient died while on therapy. CONCLUSIONS Our data support the utilization of antiviral therapy in HCV-infected patients awaiting LT as one of the strategies to prevent hepatitis C recurrence after transplantation.

High pathological risk of recurrence after surgical resection for hepatocellular carcinoma: An indication for salvage liver transplantation

Surgical resection and liver transplantation offer a 5‐year survival greater than 70% in patients with hepatocellular carcinoma, but the high recurrence rate impairs long‐term outcome after resection. Pathological data such as vascular invasion and detection of additional nodules predict recurrence and divide patients into high and low risk profile. Based on this, we proposed salvage liver transplant to resected patients in whom pathology evidenced high recurrence risk even in the absence of proven residual disease. From January 1995 to August 2003 we have evaluated 1,638 patients. Resection was indicated in 77 patients, but only 17 (22%) (all cirrhotics, 14 hepatitis C virus+) were optimal candidates for both resection and transplantation. Of them, 8 exhibited a high risk profile at pathology and were offered transplantation. Among the 8 high risk patients, 7 presented recurrence, compared with only 2 of the 9 at low risk (P = .012). Two of the high risk patients refused transplant and developed multifocal disease during follow‐up. The other 6 were enlisted and all but 1 had tumor foci in the explant. Only 1 presented extrahepatic dissemination early after transplant and died 4 months later. The others are free of disease after a median follow‐up of 45 months. Two recurrences were detected in low risk patients, 1 of them being transplanted 18 months after surgery. These data in a small series of patients confirm that pathological parameters identify patients at higher risk of recurrence, which allow them to be listed for liver transplantation without proven malignant disease. In conclusion, this policy is clinically effective and could further improve the outcome of resected patients. (Liver Transpl 2004;10:1294–1300.)

Hepatocellular carcinoma and cirrhosis. Results of surgical treatment in a European series.

OBJECTIVE The authors analyze the outcomes of patients with hepatocellular carcinoma (HCC) and cirrhosis who underwent liver resections. BACKGROUND Liver resection is the best option for HCC arising from hepatic cirrhosis. The experience of Western centers with these patients is shorter than the Asian series. METHODS Forty-eight consecutive patients with cirrhosis and HCC who underwent liver resections were studied after a similar diagnostic and therapeutic process. Survival and cumulative recurrence were calculated according to pathologic findings. RESULTS Factors influencing survival at 3 years were as follows: type of resection, absence of vascular invasion, size of the tumor, absence of satellite nodules, and the number of nodules. Factors influencing the rate of recurrence at 3 years were the presence of vascular invasion and the presence of satellite nodules. Patients with favorable prognostic factors have a good survival rate with an acceptable recurrence rate. CONCLUSIONS Identification of prognostic factors may help in the selection of the appropriate treatment for these patients with HCC and cirrhosis.

Efficacy and safety of repeated perioperative doses of recombinant factor VIIa in liver transplantation

Patients undergoing orthotopic liver transplantation (OLT) have excessive blood loss during surgery that requires blood transfusions, leading to increased postoperative morbidity and mortality. We studied the efficacy and safety of activated recombinant factor VII (rFVIIa) in reducing transfusion requirements in OLT. This multicenter, randomized, double‐blind, placebo‐controlled trial enrolled patients undergoing OLT because of cirrhosis (Child‐Turcotte‐Pugh class B or C). Patients received a repeated intravenous bolus regimen of rFVIIa 60 or 120 μg/kg or placebo. The primary efficacy endpoint was the total number of red blood cell (RBC) units transfused during the perioperative period. A total of 182 patients were analyzed for efficacy and 183 for safety. No significant effect of rFVIIa was observed on the number of RBC units transfused or intraoperative blood loss compared with the placebo group. A significantly higher number of patients in the rFVIIa study groups avoided RBC transfusion. Administration of rFVIIa but not placebo restored the preoperative prolonged prothrombin time to normal value during surgery. Patients receiving rFVIIa and placebo did not experience a significant difference in rate of thromboembolic events. Additionally, there was no statistically significant effect of rFVIIa treatment on hospitalization rate, total surgery time, and the proportion of patients undergoing retransplantation. In conclusion, use of rFVIIa during OLT significantly reduced the number of patients requiring RBC transfusion. There was no increase in thromboembolic events with rFVIIa administration compared with placebo. (Liver Transpl 2005;11:973–979.)

Hepatitis C recurrence is more severe after living donor compared to cadaveric liver transplantation

Preliminary reports suggested that hepatitis C virus (HCV) infection has a more aggressive course following living donor liver transplantation (LDLT) compared to cadaveric liver transplantation (CLT). The aim of this prospective study was to establish if HCV disease recurrence differs between LDLT and CLT. A cohort of 116 consecutive HCV‐infected patients undergoing 117 LTs in a single center from March 2000 to August 2003 were followed‐up, including systematic liver biopsies. Severe recurrence (SR) was defined as biopsy‐proven cirrhosis and/or the occurrence of clinical decompensation. After a median follow‐up of 22 months (2.6–44 months), 26 (22%) patients developed SR (decompensation in 12), involving 17 (18%) of 95 patients undergoing CLT and 9 (41%) of 22 undergoing LDLT. The 2‐year probability of presenting SR was significantly higher in LDLT compared to CLT (45% vs. 22%, P = .019). By univariate analysis LDLT (P = .019) and an ALT higher than 80 IU/L 3 months after LT (P = .022) were predictors of SR. In 93 patients from whom a liver biopsy was available 3 months after LT, a lobular necroinflammatory score >1 (P < .01), LDLT (P < .01), and biliary complications (P = .046) were associated with SR. However, the only variables independently associated with SR were LDLT (odds ratio [OR], = 2.8; 95% CI,1.19‐6.6; P = .024) and a lobular necroinflammatory score >1 (OR, 3.1; 95% CI, 1.2‐8; P = .013). In conclusion, HCV recurrence is more severe in LDLT compared to CLT. Although our results were based on a single‐center experience, they should be considered in the decision‐making process of transplant programs, since severe HCV recurrence may ultimately compromise graft and patient survival. (HEPATOLOGY 2004; 40:699–707.)