Repeat hepatectomy for colorectal liver metastases

This study includes 16 patients (9 men, 7 women; mean age 64 years) who underwent a total of 19 repeat hepatectomies for metastasis after colon (n=7) or rectal (n=9) carcinoma. All patients were reoperated for recurrent liver metastasis after the first resection (mean, 21 months; range, 7-40 months), and three had a third hepatectomy 13, 24, or 65 months after the second. Perioperative mortality was 0% and morbidity was 37%. The 3- and 5-year survival rates after the second resection were 56.8% and 28.4%, respectively, with a median survival of 42.3 months. Seven patients died (mean survival, 25.7 months; range, 9-58 months) before the end of the study. Six patients were alive with one or more recurrences, and three (24, 51, and 173 months of follow-up) were alive without known recurrence. Survival rates for repeat resections of colorectal liver metastases in selected patients were comparable with those obtained after resection of a first liver metastasis.     

Critical appraisal of the clinical and pathologic predictors of survival after resection of large hepatocellular carcinoma

HYPOTHESIS: A subset of patients with hepatocellular carcinoma (HCC) with a diameter of 10 cm or larger may benefit from hepatic resection. DESIGN: Retrospective study of a multi-institutional database. SETTING: Five major hepatobiliary centers. PATIENTS: We identified 300 patients who underwent hepatic resection for HCC 10 cm or larger. MAIN OUTCOME MEASURES: Clinical and pathologic data were collected, and prognostic factors were evaluated by univariate and multivariate analyses. Patient survival was stratified according to a clinical scoring system and pathologic T classification. RESULTS: The perioperative mortality rate was 5%. At a median follow-up of 32 months, the median survival was 20.3 months, and the 5-year actuarial survival rate was 27%. Four clinical factors-alpha-fetoprotein of 1000 ng/mL or higher, multiple tumor nodules, the presence of major vascular invasion, and the presence of severe fibrosis-were significant predictors of poor survival (all P<.05). Patients were assigned a clinical score according to the following risk factors: 1, no factor; 2, one or two factors; or 3, three or four factors. On the basis of the clinical score, patients could be stratified into only 2 distinct prognostic groups: no factor (score of 1) vs 1 or more factors (score of 2 or 3) (P<.001). In contrast, when patients were stratified according to pathologic T classification, 3 distinct groups were identified: T1 vs T2 vs T3 and T4 combined (P<.001). Fifty-six percent of the patients with a clinical score of 2 and 20% of patients with a clinical score of 3 actually had T1 or T2 disease on pathologic examination. CONCLUSIONS: Patients with large HCCs should be considered for liver resection as this treatment is associated with a 5-year survival rate exceeding 25%. Clinical predictors should not be used to exclude patients from surgical resection because these factors do not reliably predict outcome.     

Local recurrence after hepatic radiofrequency coagulation: multivariate meta-analysis and review of contributing factors

OBJECTIVE: The purpose of this study was to analyze the factors that influence local recurrence after radiofrequency coagulation of liver tumors. SUMMARY BACKGROUND DATA: Local recurrence rate varies widely between 2% and 60%. Apart from tumor size as an important risk factor for local recurrence, little is known about the impact of other factors. METHODS: An exhaustive literature search was carried out for the period from January 1, 1990 to January 1, 2004. Only series with a minimal follow-up of 6 months and/or mean follow-up of 12 months were included. Univariate and multivariate meta-analyses were carried out. RESULTS: Ninety-five independent series were included, allowing the analysis of the local recurrence rate of 5224 treated liver tumors. In a univariate analysis, tumor-dependent factors with significantly less local recurrences were: smaller size, neuroendocrine metastases, nonsubcapsular location, and location away from large vessels. Physician-dependent favorable factors were: surgical (open or laparoscopic) approach, vascular occlusion, general anesthesia, a 1-cm intentional margin, and a greater physician experience. In a multivariate analysis, significantly less local recurrences were observed for small size (P < 0.001) and a surgical (versus percutaneous) approach (P < 0.001). CONCLUSIONS: Radiofrequency coagulation by laparoscopy or laparotomy results in superior local control, independent of tumor size. The percutaneous route should mainly be reserved for patients who cannot tolerate a laparoscopy or laparotomy. The short-term benefits of less invasiveness for the percutaneous route do not outweigh the longer-term higher risk of local recurrence.     

Inhibitory and stimulatory effects of cyclosporine A on the development of regulatory T cells in vivo

BACKGROUND: Regulatory T cells (Tregs) are increasingly recognized as playing a major role in nondeletional tolerance. To avoid rejection before tolerance is established, clinical trials of tolerance induction include immunosuppressive drugs early posttransplant. It is therefore essential that immunosuppressive protocols do not block Tregs generation. Tregs function has been shown to depend upon interleukin-2 signaling, but there are limited data available on how calcineurin inhibitors influence Tregs development and function in vivo. METHODS: To study this, we used a previously established rat cardiac allograft model where donor-specific Tregs and tolerance are induced by pretransplant donor-specific blood transfusion (DSBT). RESULTS: In this model, we found that adjunction of 50 mg/kg cyclosporine (CsA) (not a lower dose, 10 mg/kg) at the time of DSBT (not at the time of transplantation) abrogates Tregs development and causes rejection. Interestingly, 10 mg/kg CsA given posttransplant (day 0-11) in the absence of pretransplant DSBT induced the development of Tregs and provoked a state of tolerance indistinguishable from the one induced by DSBT. Finally, DSBT given the day of transplantation did not promote tolerance, unless recipients also received a delayed short course (day 5-9) of 10 mg/kg CsA. CONCLUSIONS: Adjunction of high-dose CsA to pretransplant DSBT abrogates Tregs generation. On the contrary, a lower dose (10 mg/kg) of CsA promotes Tregs development either in synergy with perioperative DSBT (providing that a drug-free interval is respected) or by its own effect. These data provide new guidelines for a more tolerogenic use of calcineurin inhibitors in the clinic, particularly when immunomodulatory strategies aimed at inducing Tregs are applied.     

Anti-CD2 monoclonal antibody and tacrolimus in adult liver transplantation

BACKGROUND: Blockade of costimulation and adhesion signaling is an attractive approach to interfere with graft rejection METHODS: Between January 1997 and May 1999, forty adults having benign liver diseases were included in a prospective, randomized study comparing tacrolimus plus low-dose short-term steroids without (n=20, TAC group) or with a 10-day course of antihuman CD2 monoclonal antibody (n=20, BTI group). RESULTS: At day 7, histological rejection expressed by mean Banff scores (2.3+/-1.6 vs. 5.4+/-1.6 in the TAC group; P<0.0001) and incidence of moderate to severe rejection (score>or=6) (0 vs. 10 [50%] in the TAC group; P<0.001) were significantly lower in the BTI group. Rejection was treated in 10% (two patients) of BTI patients during the first 3 months and in 15% during the whole follow-up and in 25% (five patients) of TAC patients (P=NS). None of the BTI-patients presented with an adverse event. Three-month, 1-year, and 5-year actual patient survival rates were 100%, 95%, and 95% in the BTI group and 100%, 100%, and 85% in the TAC group. Graft survival rates were 100%, 90%, and 90% in the BTI group and 95%, 95%, and 80% in the TAC group (P=NS). The mAb had no negative impact on infectious or tumor events. CONCLUSIONS: Antihuman CD2 monoclonal antibody is a safe immunosuppressive drug which has a favorable impact on early immunological follow-up of liver transplanted patients. The antibody had no impact on late patient and graft survival.     

Sirolimus and tacrolimus trough concentrations and dose requirements after kidney transplantation in relation to CYP3A5 and MDR1 polymorphisms and steroids

BACKGROUND: CYP3A5 and MDR1 polymorphisms have been shown to influence tacrolimus blood concentrations and dose requirements. The aim is to determine whether these polymorphisms also affect sirolimus trough concentrations and dose requirements after kidney transplantation. METHODS: Eighty-five renal transplant recipients receiving sirolimus were included. Twenty-four were treated with a combined sirolimus-tacrolimus regimen. Eighty-one patients received steroids. Sirolimus and tacrolimus were adjusted to a target therapeutic window. CYP3A5 (intron 3) and MDR1 (exons 12, 21, 26) genotypes were correlated to the adjusted trough concentrations and dose requirements for both sirolimus and tacrolimus. RESULTS: There were no significant correlation between adjusted sirolimus trough concentrations or dose requirements and genetic polymorphisms. In a multiple regression model, adjusted-prednisone dose was involved with a positive or negative effect when considering sirolimus dose requirements or adjusted concentrations, respectively. In the subgroup of patients treated by tacrolimus and sirolimus, adjusted tacrolimus doses were higher in patients carrying at least one CYP3A5 *1 allele (median 0.083 vs. 0.035 mg/kg for CYP3A5*3/*3 patients, P<0.05). Adjusted-prednisolone dose and CYP3A5 polymorphism explained up to 61% of the variability in tacrolimus dose requirements. CONCLUSIONS: Unlike tacrolimus, sirolimus adjusted trough concentrations and dose requirements seem not affected by CYP3A5 and MDR1 polymorphisms. Adjusted-prednisone dose has a significant impact on tacrolimus and sirolimus dose requirements.     

Fast-track coronary artery bypass grafting surgery under general anesthesia with remifentanil and spinal analgesia with morphine and clonidine

OBJECTIVE: Effective postoperative analgesia is a critical part of fast-track cardiac surgery. This study compared the postoperative analgesic effect of fast-track anesthesia with remifentanil and spinal morphine and clonidine with that of sufentanil anesthesia followed by patient-controlled administration of intravenous morphine. DESIGN: Prospective, blinded, randomized study. SETTING: Single private institution. PARTICIPANTS: Forty patients selected for coronary artery bypass graft surgery allocated randomly into 2 groups. INTERVENTIONS: General anesthesia was performed with etomidate, isoflurane, cisatracurium, and either remifentanil (0.10-0.25 microg/kg/min) or sufentanil (up to 3.5 microg/kg). In the remifentanil group, patients received spinal morphine (4 microg/kg) and clonidine (1 microg/kg) before induction. Postoperatively, patients in both groups were connected to an intravenous patient-controlled analgesia (PCA) morphine pump that delivered a 1-g bolus with a 7-minute lockout interval. MEASUREMENTS AND MAIN RESULTS: Patients were evaluated for pain on a visual analog scale (VAS), at rest and on deep breathing, and for intravenous PCA morphine consumption during 24 hours. The intravenous PCA morphine 24-hour cumulative dose was lower in the fast-track than in the control group (15.8+/-12.6 v 32.7+/-22.3 mg, p<0.05). Before extubation, VAS scores were higher in the fast-track group, but after they were lower both at rest and during deep breathing. Extubation delay was shorter in the fast-track group (156.5+/-46.1 v 272+/-116.4 minutes, p<0.05). CONCLUSION: The combination of anesthesia with remifentanil and spinal analgesia with morphine and clonidine produces effective analgesia after coronary artery surgery and a rapid extubation time.