Repeat hepatic resection versus radiofrequency ablation for recurrent hepatocellular carcinoma: retrospective multicentre study.

BACKGROUND: The therapeutic value of repeat hepatic resection (rHR) or radiofrequency ablation (RFA) for recurrent hepatocellular carcinoma (HCC) is unknown. This study aimed to investigate the safety and efficacy of rHR or RFA. METHODS: This was a retrospective multicentre study of patients with recurrent HCC within the Milan criteria who underwent rHR or RFA at nine university hospitals in China and Italy between January 2003 and January 2018. Survival after rHR or RFA was examined in unadjusted analyses and after propensity score matching (1 : 1). RESULTS: Of 847 patients included, 307 and 540 underwent rHR and RFA respectively. Median overall survival was 73.5 and 67.0 months after rHR and RFA respectively (hazard ratio 1.01 (95 per cent c.i. 0.81 to 1.26)). Median recurrence-free survival was longer after rHR versus RFA (23.6 versus 15.2 months; hazard ratio 0.76 (95 per cent c.i. 0.65 to 0.89)). These results were confirmed after propensity score matching. RFA was associated with lower morbidity of grade 3 and above (0.6 versus 6.2 per cent; P < 0.001) and shorter hospital stay (8.0 versus 3.0 days, P < 0.001) than rHR. CONCLUSION: rHR was associated with longer recurrence-free survival but not overall survival compared with RFA.

The impact of carbapenemase-producing Enterobacteriaceae colonization on infection risk after liver transplantation: a prospective observational cohort study.

OBJECTIVE: To investigate the impact of colonization with carbapenemase-producing Enterobacteriaceae (CPE) on the CPE infection risk after liver transplantation (LT). METHODS: Prospective cohort study of all adult patients undergoing LT at our centre over an 8-year period (2010-2017). Individuals were screened for CPE colonization by rectal swabs at inclusion onto the waiting list, immediately before LT and weekly after LT until hospital discharge. Asymptomatic carriers did not receive decolonization, anti-CPE prophylaxis or pre-emptive antibiotic therapy. Participants were followed up for 1 year after LT. RESULTS: We analysed 553 individuals who underwent a first LT, 38 were colonized with CPE at LT and 104 acquired colonization after LT. CPE colonization rates at LT and acquired after LT increased significantly over the study period: incidence rate ratios (IRR) 1.21 (95% CI 1.05-1.39) and 1.17 (95% CI 1.07-1.27), respectively. Overall, 57 patients developed CPE infection within a median of 31 (interquartile range 11-115) days after LT, with an incidence of 3.05 cases per 10 000 LT-recipient-days and a non-significant increase over the study period (IRR 1.11, 95% CI 0.98-1.26). In multivariable analysis, CPE colonization at LT (hazard ratio (HR) 18.50, 95% CI 6.76-50.54) and CPE colonization acquired after LT (HR 16.89, 95% CI 6.95-41.00) were the strongest risk factors for CPE infection, along with combined transplant (HR 2.60, 95% CI 1.20-5.59), higher Model for End-Stage Liver Disease at the time of LT (HR 1.03, 95% CI 1.00-1.07), prolonged mechanical ventilation (HR 2.63, 95% CI 1.48-4.67), re-intervention (HR 2.16, 95% CI 1.21-3.84) and rejection (HR 2.81, 95% CI 1.52-5.21). CONCLUSIONS: CPE colonization at LT or acquired after LT were the strongest predictors of CPE infection. Prevention strategies focused on LT candidates and recipients colonized with CPE should be investigated.

Impact of primary cancer features on behaviour of colorectal liver metastases and survival after hepatectomy.

Background: Markers of tumour biology may be valuable prognostic indicators after hepatic resection of colorectal cancer liver metastases (CRLMs). Identification of the aggressiveness of these metastases might inform the appropriateness of hepatic surgery. Methods: Patients undergoing liver resection for CRLMs between January 2001 and July 2013 in four tertiary hospitals were reviewed. A mathematical model to estimate CRLM doubling times was constructed for patients with metachronous metastases. Tumour doubling time was investigated in relation to the features of colorectal cancer, including KRAS status. The hazard rate for recurrence and death following hepatectomy was explored through the Kernel-smoothed estimator. Results: Of 1063 patients undergoing liver resection for CRLMs, 361 with metachronous metastases undergoing single-stage hepatectomy were analysed. The mean doubling time in patients not receiving chemotherapy between surgery for colorectal cancer and CRLM was 71·4 days. Tumour doubling time was shorter in patients with more advanced primary tumour stages, with mutant KRAS and in those who did not receive chemotherapy. For fast-growing CRLMs (doubling time less than 48 days), the risk of recurrence was highest within the first postoperative year, and was about 7 per cent per month. Conclusion: Primary features of colorectal cancer were linked to aggressiveness of CRLMs as measured by doubling time.

Hepatobiliary Scintigraphy in the Preoperative Evaluation of Potential Living Liver Donors.

BACKGROUND: Graft selection strategy in living donor liver transplantation (LDLT) is usually multifactorial, but special attention is paid to the determination of donor liver volumes to minimize any risk of posthepatectomy liver failure (PHLF). Hepatobiliary scintigraphy (HBS) with single-photon-emission computed tomography allows for the measurement of total and future liver remnant function (FLR-F) and has been shown to predict the risk of PHLF more accurately than liver volumetry. METHODS: Since November 2016, HBS has been performed at our Institution in every candidate to major hepatectomy, including potential living liver donors. RESULTS: Thirty-seven consecutive patients were submitted to HBS, of whom 7 were potential living liver donors. After completed hepatectomy (n = 27), the median FLR-F of patients who developed PHLF (n = 9) was 1.72%/min/m2 (range 1.40-2.78) compared to that of patients who did not (n = 18), which was 4.02%/min/m2 (range 1.15-12.08). Three donors underwent operations (1 right hepatectomy and 2 left hepatectomies). In the only donor who developed PHLF, the FLR accounted for the 37% of the total liver volume, whereas the FLR represented only the 31% of the total liver function (TL-F = 11.29%/min) with a resulting FLR-F of 2.05%/min/m2. CONCLUSIONS: The present study suggests that a non-invasive low-cost exam such as HBS may be a promising tool to predict PHLF not only in neoplastic patients but also to evaluate potential living donors. Larger studies are needed to draw any conclusion regarding the benefits of HBS in the living liver donor workup.

Membrane human equilibrative nucleoside transporter 1 is associated with a high proliferation rate and worse survival in resected intrahepatic cholangiocarcinoma patients not receiving adjuvant treatments.

Human equilibrative nucleoside transporter 1 (hENT-1) is a membrane nucleoside transporter mediating the intracellular uptake of nucleosides and their analogues. hENT-1 was recently reported to have a predictive role in intrahepatic cholangiocarcinoma (iCC) patients receiving adjuvant gemcitabine-based chemotherapy, but its biological and clinical significance in iCC remains unsettled. This study investigated the role of hENT-1 in regulating tumour growth and predicting the survival of 40 resected iCC patients not receiving adjuvant treatments. hENT-1 expression was found to be significantly higher in iCC than in the matched non-tumoural liver. Patients harbouring hENT-1 localised on the tumour cell membrane had a worse overall survival than membrane hENT-1-negative patients (median 21.2 months vs 30.3 months, p = 0.031), with an adjusted hazard ratio of 2.8 (95% confidence interval 1.01-7.76). Moreover, membrane hENT-1-positive patients had a higher percentage of Ki67-positive cells in tumour tissue than membrane hENT-1-negative patients (median 23% vs 5%, p < 0.0001). Functional analyses in iCC cell lines revealed that hENT-1 silencing inhibited cell proliferation and induced apoptosis in HUH-28 cells expressing hENT-1 on the cell membrane, but not in SNU-1079 cells expressing the transporter only in the cytoplasm. Overall, these findings suggest that membrane hENT-1 is involved in iCC proliferation and associated with worse survival in resected iCC patients. Further prospective studies on larger cohorts are required to confirm these results and better define the potential prognostic role of membrane hENT-1 in this setting of patients.

Average treatment effect of hepatic resection versus locoregional therapies for hepatocellular carcinoma.

BACKGROUND: When comparing the efficacy of surgical and non-surgical therapies for hepatocellular carcinoma (HCC), a major limitation is the causal inference problem. This concerns the impossibility of seeing both outcomes of two different treatments for the same individual at the same time because one is inevitably missing. This aspect can be addressed methodologically by estimating the so-called average treatment effect (ATE). METHODS: To estimate the ATE of hepatic resection over locoregional therapies for HCC, data from patients treated in two tertiary care settings between August 2000 and December 2014 were used to obtain counterfactual outcomes using an inverse probability weight survival adjustment. RESULTS: A total of 1585 patients were enrolled: 815 underwent hepatic resection, 337 radiofrequency ablation (RFA) and 433 transarterial chemoembolization (TACE). The option of operating on all patients who had tumour ablation returned an ATE of +9·8 months for resection (effect size 0·111; adjusted P = 0·064). The option of operating on all patients who had TACE returned an ATE of +27·9 months (effect size 0·383; adjusted P < 0·001). The ATE of surgery was negligible in patients undergoing ablation for very early HCCs (effect size 0·027; adjusted P = 0·627), independently of albumin-bilirubin (ALBI) grade; or in patients with ALBI liver function grade 2 (effect size 0·083; adjusted P = 0·213), independently of tumour stage. In all other instances, the ATE of surgery was notably greater. Operating on patients who had TACE with multinodular HCC beyond the Milan criteria resulted in a mild ATE (effect size 0·140; adjusted P = 0·037). CONCLUSION: ATE estimation suggests that hepatic resection is a better treatment option than ablation and TACE in patients with HCC.

Impact of preoperative infection on outcome after liver transplantation.

BACKGROUND: Bacterial infection in patients with liver failure can lead to a dramatic clinical deterioration. The indications for liver transplantation and outcome in these patients is still controversial. METHODS: All adult patients who underwent liver transplantation between 1 January 2010 and 31 December 2015 were selected from an institutional database. Characteristics of the donors and recipients, and clinical, biochemical and surgical parameters were retrieved from the database. Post-transplant survival rates and complications, including grade III-IV complications according to the Dindo-Clavien classification, were compared between patients with an infection 1 month before transplantation and patients without an infection. RESULTS: Eighty-four patients with an infection had statistically significant higher Model for End-stage Liver Disease (MELD), D-MELD and Balance of Risk (BAR) scores and a higher rate of acute-on-chronic liver failure compared with findings in 343 patients with no infection. The rate of infection after liver transplantation was higher in patients who had an infection before the operation: 48 per cent versus 30·6 per cent in those with no infection before transplantation (P = 0·003). The percentage of patients with a postoperative complication (42 versus 40·5 per cent respectively; P = 0·849) and the 90-day mortality rate (8 versus 6·4 per cent; P = 0·531) was no different between the groups. Multivariable analysis showed that a BAR score greater than 18 and acute-on-chronic liver failure were independent predictors of 90-day mortality. CONCLUSION: Bacterial infection 1 month before liver transplantation is related to a higher rate of infection after transplantation, but does not lead to a worse outcome.

Effect of age on survival in patients undergoing resection of hepatocellular carcinoma.

BACKGROUND: The benefit of surgical intervention for cancer should be estimated in relation to the life expectancy of the general population. The aim of this study was to provide a measure of relative survival after hepatectomy for hepatocellular carcinoma (HCC). METHODS: Consecutive patients with liver cirrhosis and HCC who underwent hepatectomy were divided into age quartiles for analysis. Short- and mid-term survival rates were used to estimate survival until death for all patients, in relation to age and other co-variables. Years of life lost (YLL) were estimated using a reference cohort, derived from the general population matched for sex, age and year of diagnosis. RESULTS: Some 919 patients were included in the study. The following age quartiles were identified: less than 60 years (229 patients), 60-66 years (230), 67-70 years (231) and over 70 years (229). Postoperative mortality rates were similar between age quartiles, as were survival rates up to 3 years (P = 0·404). A statistically significant reduction in 5-10-year survival rates was observed with ageing (P = 0·001). Relative survival calculation showed that the youngest age quartile (less than 60 years) experienced the longest entire postoperative lifespan (15·6 years) but also the greatest number of YLL (11·0 years). Patients aged over 70 years had the shortest entire postoperative lifespan (6·4 years) but also the smallest number of YLL (3·7 years). CONCLUSION: Although survival after liver resection for HCC is shortest in elderly patients, relative survival estimates suggest that hepatectomy can be of benefit in these patients, with a small loss of the entire individual lifespan.

Effect of age on native kidney function after adult intestinal transplants on long-term follow-up.

BACKGROUND: Kidney function usually deteriorates after intestinal transplant, with prevalence of renal failure almost 20% after 5 years. We report our results on adults from single institution over >10 years. METHODS: Forty-six patients were transplanted with 22 survivors; we divided them in 2 groups: Group 1, recipients with creatinine>1.2 mg/dL (normal, 0.50-1.2) and Group 2, normal creatinine. Group 1 included 12 patients (9 males) with a mean age of 42.8 years; all lived at home, with normal creatinine at transplant (apart from 1 patient with a creatinine of 1.6 mg/dL), and were mainly transplanted for short bowel syndrome. One underwent retransplantation. Immunosuppression was based on alemtuzumab (8 recipients) plus tacrolimus (FK). Group 2 included 10 patients (6 males) with a mean age of 34.7 years; all lived at home, had normal creatinine at transplantation, and were mainly transplanted for short bowel syndrome. Immunosuppression was mainly based on alemtuzumab (8 recipients) plus FK. RESULTS: There were no relevant differences between the 2 groups regarding number of recipients, sex, baseline creatinine at transplant, reason for transplantation, retransplantation, immunosuppression, antifungal or antiviral therapy, hospitalization, total parenteral nutrition (or fluids), or stoma. The only relevant difference was age (P=.04); patients with deteriorated kidney function or altered creatinine were found to be older.

Is resectable hepatocellular carcinoma a contraindication to liver transplantation? A novel decision model based on "number of patients needed to transplant" as measure of transplant benefit.

BACKGROUND & AIMS: Number-needed-to-treat is used in assessing the effectiveness of a health-care intervention, and reports the number of patients who need to be treated to prevent one additional bad outcome. Although largely used in medical literature, there are no studies measuring the benefit of liver transplantation (LT) over hepatic resection (HR) for hepatocellular carcinoma (HCC) in terms of "Number of patients needed to transplant (NTT)." EXCLUSION CRITERIA: Child-Turcotte-Pugh (CTP) Classes B-C, very large (>10 cm) and multi-nodular (>2 nodules) tumours, macroscopic vascular invasion and extra-hepatic metastases. STUDY POPULATION: 1028 HCC cirrhotic patients from one Eastern (n=441) and two Western (n=587) surgical units. Patient survival observed after HR by proportional hazard regression model was compared to that predicted after LT by the Metroticket calculator. The benefit obtainable from LT compared to resection was analysed in relationship with number of nodules (modelled as ordinal variable: single vs. oligonodular), size of largest nodule (modelled as a continuous variable), presence of microscopic vascular invasion (MVI), and time horizon from surgery (5-year vs. 10-year). RESULTS: 330 patients were beyond the Milan criteria (32%) and 597 (58%) had MVI. The prevalence of MVI was 52% in patients within Milan criteria and 71% in those beyond (p<0.0001). In the 5-year transplant benefit analysis, nodule size and HCC number were positive predictors of transplant benefit, while MVI had a strong negative impact on NTT. Transplantation performed as an effective therapy (NTT <5) only in oligonodular HCC with largest diameter >3cm (beyond conventional LT criteria) when MVI was absent. The 10-year scenario increased drastically the transplant benefit in all subgroups of resectable patients, and LT became an effective therapy (NTT <5) for all patients without MVI whenever tumor extension and for oligonodular HCC with MVI within conventional LT criteria. CONCLUSIONS: Based on NTT analysis, the adopted time horizon (5-year vs. 10-year scenario) is the main factor influencing the benefit of LT in patients with resectable HCC and Child A cirrhosis.

Assessment of perioperative transfusion requirement for cirrhotic patients undergoing elective hepatectomy.

BACKGROUND: The possibility of outlining a risk profile for perioperative blood transfusion of cirrhotic patients submitted to hepatic resection can help to rationalize transfusion policy. METHODS: Data from 323 hepatic resections, performed in cirrhotic patients, were reviewed. Bootstrap and a leave-one-out logistic regressions were applied to test the accuracy of available risk scores for peri-operative transfusion identified from PubMed search of the last 20 years, to refine them, and to provide internal validation for present results. RESULTS: One-hundred-six patients (32.8%) required blood transfusions during either intra- and/or postoperative. The predictive accuracy of three identified risk scores was poor with the area under receiver operating characteristics (AUROC) curves <0.70 in all cases. Tumor diameter, hemoglobin and presence of coronary artery disease were confirmed, in the present cohort, as predictors of blood transfusion together with serum albumin and bilirubin. The leave-one-out logistic regression results in an AUROC of 0.80, and of 0.79 for internal validation, significantly higher than that of the three scores tested (P<0.001). A Maximal Surgical Blood Order Schedule stratification was proposed. CONCLUSION: The risk profile for transfusion of cirrhotic patients undergoing hepatectomy can be better assessed with a model that combines already known clinical factors and hepatic function indexes.

Isolated intestinal transplant for chronic intestinal pseudo-obstruction in adults: long-term outcome.

BACKGROUND: Chronic intestinal pseudo-obstruction (CIPO) has been treated in adults by total parenteral nutrition (TPN) or, if complications arise, by multivisceral transplantation because the stomach is often involved. Eleven adults with CIPO were transplanted by intestinal graft in our center from 2000 to 2011. METHODS: Nine patients underwent isolated intestinal transplant and 2 patients had multivisceral transplant. Immunosuppression was represented by FK and steroids plus induction with alemtuzumab, daclizumab, or thymoglobulin. Average age at transplant was 33.5 years. We reported 1 graftectomy, followed by retransplantation. RESULTS: Seven patients are currently alive with working small bowel; cause of death was infection in the 4 remaining cases. In 9 isolated intestinal transplants, we performed different digestive reconstructions to allow gastric emptying. In 2 cases we were forced, after transplant, to perform ileostomy to improve intestinal motility. Graft and patient survival after 5 years are 60% and 70%, respectively, while after 10 years, 45% and 56%, respectively. CONCLUSIONS: Adults with CIPO and irreversible TPN complications benefit from isolated intestinal transplant with different surgical techniques to empty the native stomach: this strategy achieves good gastric emptying, with effective establishment of oral feeding and graft and patient survivals comparable to isolated intestinal transplant for short bowel syndrome.

Induction therapy in adult intestinal transplantation: reduced incidence of rejection with "2-dose" alemtuzumab protocol.

The incidence of early rejection after intestinal transplantation correlates with heightened risk of graft loss and mortality. Many different induction or pre-conditioning protocols have been reported in the last 10 yr to improve outcomes; however, sepsis remains prevalent and diminishes long-term results. We recently began a "2-dose" alemtuzumab trial protocol - 15 mg at day 0 and 15 mg repeated on day 7 - with the hope of reducing our infection rate. We compared three different protocols used at our institution (daclizumab, conventional "4-dose" alemtuzumab, and "2-dose" alemtuzumab). There was a significantly lower rate of early rejection with the "2-dose" alemtuzumab protocol in our study group of mainly (88%) intestinal grafts without accompanying liver engraftment with its protective immunologic effect. Sepsis remained low. Longer follow-up will be required to evaluate the effects of this new protocol on longer-term outcomes.

Induction therapy with alemtuzumab (campath) in combined liver-kidney transplantation: University of Bologna experience.

BACKGROUND: Combined liver-kidney transplantation (LKT) is considered to be a safe procedure, but the appropriate immunosuppressive regimen is unclear. PATIENTS AND METHODS: Between January 1997 and October 2011, 55 patients were listed for LKT: 45 (82%) were effectively transplanted, 5 (9.2%) died whereon here the waiting list, 3 (5.5%) temporarily out of waiting list, 1 (1.8%) was on waiting list and 1 (1.8%) refused LKT. Five LKTs treated with cyclosporine (CyA) were excluded from the analysis. Mean recipient age was 50.32 ± 10.32 years (14-65), MELD score at time of LKT was 19.22 ± 4.69 (8-29), mean waiting list time was 8.14 ± 9.50 months (0.1-35.76), and follow-up, 4.09 ± 3.02 years (0.01-10.41). Main indications for LKT were policystic disease (n = 15; 37%), hepatitis virus C (HCV)-related cirrhosis (n = 9; 22%) metabolic disease (n = 5; 13%), hepatitis virus B (HBV) cirrhosis (n = 4; 10%), alcoholic cirrhosis (n = 4; 10%), and cholestatic disease (n = 3; 8%). Immunosuppressive regimen was based on tacrolimus and steroids in 40 cases with induction therapy with alemtuzumab (Campath; 0.3 mg/kg) in 13 of 40 instances cases administered on day 0 and day 7. RESULTS: Postoperative mortality was 2.5%. Acute cellular rejection episodes were biopsy-proven in 2 (5%) cases, post-LKT infections developed in 17 cases (42.5%), and de novo cancer developed in 3 (7.5%) cases. Similar 5-year overall survivals were obtained irrespective of the LKT indication: 100% in cholestatic and alcoholic cirrhosis patients, 86% in policystic disease, 75% in metabolic disease and HBV patients, and 66% in HCV cirrhosis. Overall survivals for the alemtuzumab vs without-induction therapy groups at 1, 3, and 5-years were 100%, 85.7%, and 85.7% vs 76%, 76%, and 70%, respectively (P = .04). CONCLUSION: An immunosuppressive regimen based on tacrolimus and steroids with induction therapy with alemtuzumab was safe, with excellent long-term results for combined LKT.

The use of social networking to explore knowledge and attitudes toward organ donation in Italy.

BACKGROUND: Currently, online social media have become increasingly popular and can provide the opportunity to provide and acquire information regarding knowledge and attitudes toward organ donation and transplantation. To evaluate participants' knowledge about organ donation, information sources and donation principles, an on-line survey was distributed through social network in Italy. METHODS: 10584 persons were invited to respond to the questionnaire, the response rate was 22.8% and a total of 2258 complete responses were analyzed. RESULTS: The majority of participants were in favour of organ donation (94.9%), but this proportion decreased when asking for consent to donation of a family member's organs (75.2%; P<0.001). Internet represented a considerable proportion of information sources (37.2%), that were much less frequently represented by family doctors (5.6%) and school education (18.6%). Conversely, 68.5% of participants think that family doctors should provide information regarding donation and 81.9% think schools should also provide such education (P<0.001). A good knowledge about donation principles was the main factor associated with a positive attitude toward donation (P<0.001). CONCLUSION: Efforts must be aimed at involving schools and family doctors in education about donation; the use of social networks can represent a way of improving such knowledge.

Can the dropout risk of candidates with hepatocellular carcinoma predict survival after liver transplantation?

In the last US national conference on liver transplantation for hepatocellular carcinoma (HCC), a continuous priority score, that incorporates model for end-stage liver disease (MELD), alpha-fetoprotein and tumor size, was recommended to ensure a more equitable liver allocation. However, prioritizing highest alpha-fetoprotein levels or largest tumors may select lesions at a higher risk for recurrence; similarly, patients with higher degree of liver failure could have lower postoperative survival. Data from 300 adult HCC recipients were reviewed and the proposed HCC-MELD equation was applied to verify if it can predict post-transplantation survival. The 5-year survival and recurrence rates after transplantation were 72.8 and 13.5%, respectively. Cox regression analysis confirmed HCC-MELD as predictive of both postoperative survival and recurrence (p < 0.001). The 5-year predicted survival and recurrence rates were plotted against the HCC-MELD-based dropout probability: the higher the dropout probability while on waiting list, the lower the predicted survival after transplantation, that is worsened by hepatitis C positivity; similarly, the higher the predicted HCC recurrence rate after transplantation. The HCC priority score could predict the postoperative survival of HCC recipients and could be useful in selecting patients with greater possibilities of survival, resulting in higher post-transplantation survival rates of HCC populations.

Safety of hepatic resection in overweight and obese patients with cirrhosis.

BACKGROUND: The simultaneous incremental increase in incidence of both obesity and hepatocellular carcinoma (HCC) will soon lead to more overweight and obese patients with cirrhosis needing surgery. At present, little is known about postoperative mortality and morbidity in such patients. This study investigated outcomes after hepatectomy in relation to obesity in a homogeneous cohort of patients with cirrhosis. METHODS: Perioperative data from 235 patients with cirrhosis who had hepatectomy for HCC were related to the presence of normal bodyweight (body mass index (BMI) 18.5-24.9 kg/m(2)), overweight (BMI 25.0-29.9 kg/m(2)) and obesity (BMI at least 30 kg/m(2)). Complications after surgery were graded according to the expanded Accordion Severity Classification of Postoperative Complications (T92). RESULTS: One hundred and one patients (43.0 per cent) were of normal bodyweight, 88 (37.4 per cent) were overweight and 46 (19.6 per cent) were obese; none was underweight. Overweight and obese groups showed a male preponderance (P = 0.024), and metabolic disorders were frequently the cause of cirrhosis in these patients (P < 0.001 and P = 0.014 for non-B non-C hepatitis and alcoholic cirrhosis respectively). Liver function tests, tumour stage and extent of hepatectomy did not significantly differ between BMI groups. The intraoperative course and postoperative mortality were unaffected by BMI. Overweight and obese patients had significantly more mild respiratory complications (P = 0.044). Severe complications and organ system (including liver) failure were not significantly affected by BMI. CONCLUSION: Hepatic resection can be performed safely in overweight and obese patients with cirrhosis, although morbidity is increased in these patients.

Sirolimus in liver transplant recipients: a large single-center experience.

Sirolimus (SRL) is a newer immunosuppressant whose possible benefits and side effects in comparison to calcineurin inhibitors (CNIs) still have to be addressed in the liver transplantation setting. We report the results of the use of SRL in 86 liver transplant recipients, 38 of whom received SRL as the main immunosuppressant in a CNI-sparing regimen. Indications for the use of SRL were: impaired renal function (n = 32), CNI neurotoxicity (n = 16), hepatocellular carcinoma (HCC) at high risk of recurrence (n = 21), recurrence of HCC (n = 6), de novo malignancies (n = 4), cholangiocarcinoma (n = 1), and the need to reinforce immunosuppression (n = 6). Among patients on SRL-based treatment, four episodes of acute rejection were observed, three of which occurred during the first postoperative month. Renal function significantly improved when sirolimus was introduced within the third postoperative month, while no change was observed when it was introduced later. Neurological symptoms resolved completely in 14/16 patients. The 3-year recurrence-free survival of patients with HCC on SRL was 84%. Sixty-two patients developed side effects that required drug withdrawal in seven cases. There was a reduced prevalence of hypertension and new-onset diabetes among patients under SRL. In conclusion, SRL was an effective immunosuppressant even when used in a CNI-sparing regimen. It was beneficial for patients with recently developed renal dysfunction or neurological disorders.

Harm and benefits of primary liver resection and salvage transplantation for hepatocellular carcinoma.

Primary transplantation offers longer life-expectancy in comparison to hepatic resection (HR) for hepatocellular carcinoma (HCC) followed by salvage transplantation; however, livers not used for primary transplantation can be reallocated to the remaining waiting-list patients, thus, the harm caused to resected patients could be balanced, or outweighed, by the benefit obtained from reallocation of livers originating from HCC patients first being resected. A Markov model was developed to investigate this issue based on literature data or estimated from the United Network for Organ Sharing database. Markov model shows that primary transplantation offers longer life-expectancy in comparison to HR and salvage transplantation if 5-year posttransplant survival remains higher than 60%. The balance between the harm for resected patients and the benefit for the remaining waiting list depends on (a) the proportion of HCC candidates, (b) the percentage shifted to HR and (c) the median expected time-to-transplant. Faced with a low proportion of HCC candidates, the harm caused to resected patients was higher than the benefit that could be obtained for the waiting-list population from re-allocation of extra livers. An increased proportion of HCC candidates and/or an increased median time-to-transplant could lead to a benefit for waiting-list patients that outweighs this harm.