Discarded livers tested by normothermic machine perfusion in the VITTAL trial: Secondary end points and 5-year outcomes.

Normothermic machine perfusion (NMP) enables pretransplant assessment of high-risk donor livers. The VITTAL trial demonstrated that 71% of the currently discarded organs could be transplanted with 100% 90-day patient and graft survivals. Here, we report secondary end points and 5-year outcomes of this prospective, open-label, phase 2 adaptive single-arm study. The patient and graft survivals at 60 months were 82% and 72%, respectively. Four patients lost their graft due to nonanastomotic biliary strictures, one caused by hepatic artery thrombosis in a liver donated following brain death, and 3 in elderly livers donated after circulatory death (DCD), which all clinically manifested within 6 months after transplantation. There were no late graft losses for other reasons. All the 4 patients who died during the study follow-up had functioning grafts. Nonanastomotic biliary strictures developed in donated after circulatory death livers that failed to produce bile with pH >7.65 and bicarbonate levels >25 mmol/L. Histological assessment in these livers revealed high bile duct injury scores characterized by arterial medial necrosis. The quality of life at 6 months significantly improved in all but 4 patients suffering from nonanastomotic biliary strictures. This first report of long-term outcomes of high-risk livers assessed by normothermic machine perfusion demonstrated excellent 5-year survival without adverse effects in all organs functioning beyond 1 year (ClinicalTrials.gov number NCT02740608).

Introduction of the Concept of Diagnostic Sensitivity and Specificity of Normothermic Perfusion Protocols to Assess High-Risk Donor Livers.

Normothermic machine perfusion (NMP) allows objective assessment of donor liver transplantability. Several viability evaluation protocols have been established, consisting of parameters such as perfusate lactate clearance, pH, transaminase levels, and the production and composition of bile. The aims of this study were to assess 3 such protocols, namely, those introduced by the teams from Birmingham (BP), Cambridge (CP), and Groningen (GP), using a cohort of high-risk marginal livers that had initially been deemed unsuitable for transplantation and to introduce the concept of the viability assessment sensitivity and specificity. To demonstrate and quantify the diagnostic accuracy of these protocols, we used a composite outcome of organ use and 24-month graft survival as a surrogate endpoint. The effects of assessment modifications, including the removal of the most stringent components of the protocols, were also assessed. Of the 31 organs, 22 were transplanted after a period of NMP, of which 18 achieved the outcome of 24-month graft survival. The BP yielded 94% sensitivity and 50% specificity when predicting this outcome. The GP and CP both seemed overly conservative, with 1 and 0 organs, respectively, meeting these protocols. Modification of the GP and CP to exclude their most stringent components increased this to 11 and 8 organs, respectively, and resulted in moderate sensitivity (56% and 44%) but high specificity (92% and 100%, respectively) with respect to the composite outcome. This study shows that the normothermic assessment protocols can be useful in identifying potentially viable organs but that the balance of risk of underuse and overuse varies by protocol.

Impact of an enhanced recovery after surgery protocol on short-term outcomes in elderly patients undergoing pancreaticoduodenectomy.

BACKGROUND: To determine whether the short-term benefits associated with an enhanced recovery after surgery programme (ERAS) following pancreaticoduodenectomy (PD) vary with age. METHODS: 830 consecutive patients who underwent PD between January 2009 and March 2019 were divided according to age: elderly (≥75 years) vs. non-elderly patients (<75 years). Within each age group, cohort characteristics and outcomes were compared between patients treated pre- and post-ERAS (ERAS was systematically introduced in December 2012). Univariable and multivariable analysis were then performed, to assess whether ERAS was independently associated with length of hospital stay (LOS). RESULTS: Of the entire cohort, 577 of 830 patients (69.5%) were managed according to an ERAS protocol, and 170 patients (20.5%) were aged ≥75 years old. Patients treated post-ERAS were significantly more comorbid than those pre-ERAS, with a mean Charlson Comorbidity Index of 4.6 vs. 4.1 (p < 0.001) and 6.0 vs. 5.7 (p = 0.039) for the non-elderly and elderly subgroups, respectively. There were significantly fewer medical complications in non-elderly patients treated post-ERAS compared to pre-ERAS (12.4% vs. 22.4%; p = 0.002), but not in elderly patients (23.6% vs. 14.0%; p = 0.203). On multivariable analysis, ERAS was independently associated with reduced LOS in both elderly (14.8% reduction, 95% CI: 0.7-27.0%, p = 0.041) and non-elderly patients (15.6% reduction, 95% CI: 9.2-21.6%, p < 0.001), with the effect size being similar in each group. CONCLUSION: ERAS protocols can be safely applied to patients undergoing pancreaticoduodenectomy irrespective of age. Implementation of an ERAS protocol was associated with a significant reduction in postoperative LOS in both elderly and non-elderly patients, despite higher comorbidity in the post-ERAS period.

Recurrence patterns of pancreatic cancer after pancreatoduodenectomy: systematic review and a single-centre retrospective study.

BACKGROUND: Positive margins in pancreatoduodenectomy (PD) for pancreatic cancer, specifically the superior mesenteric artery (SMA) margin, are associated with worse outcomes. Local therapies targeting these margins could impact on recurrence. This study analysed recurrence-patterns to identify whether strategies to control local disease could have a meaningful impact. METHODS: (I) Systematic review to define recurrence patterns and resection margin status. (II) Additional retrospective study of PD performed at our centre. RESULTS: In the systematic review, 23/617 evaluated studies were included (n = 3815). Local recurrence was observed in 7-69%. SMA margin (6 studies) was positive in 15-35%. In the retrospective study (n = 204), local recurrence was more frequently observed with a positive SMA margin (66 vs.45%; p = 0.005). Furthermore, in a multivariate cox-proportional hazard model, only a positive SMA margin was associated with disease recurrence (HR 1.615; 95%CI 1.127-2.315; p = 0.009). Interestingly, median overall survival was 20 months and similar for patients who developed local only, metastases only or simultaneous recurrence (p = 0.124). CONCLUSION: Local recurrence of pancreatic cancer is common and associated with similar mortality rates as those who present with simultaneous or metastatic recurrence. Involvement of the SMA margin is an independent predictor for disease progression and should be the target of future adjuvant local therapies.

Risk adjusted assessment of individual surgeon's pancreatic fistula outcomes.

BACKGROUND: Post-operative pancreatic fistula (POPF) is a major cause of morbidity following pancreatoduodenectomy. The risk of POPF varies between individuals and thus assessment without risk adjustment is crude. However, despite the availability of numerous scores to determine risk, no study has provided a risk adjusted assessment of POPF outcomes. METHODS: The observed and risk adjusted occurrence of POPF from consecutive patients operated upon by eight surgeons were recorded. Surgeons varied in experience from newly appointed (n = 5) to established (n = 3). CUSUM (cumulative sum) analysis was used to assess performance. RESULTS: 104 POPF occurred among 519 patients (20.0%). The occurrence of POPF was significantly lower among experienced surgeons (20/186, 10.7% vs 84/333, 25.2%; p < 0.001). Following risk adjustment surgeons observed 16.6 fewer to 6.5 excess POPF per 100 patients than predicted. Analysis of the CUSUM plots demonstrated the experienced surgeons performed steadily with a gradual reduction in observed POPF compared to what was predicted. The new surgeon's performance was less consistent and evidence of a learning curve was observed with steady improvement occurring after 50-70 patients. CONCLUSIONS: Risk adjusted assessment of POPF demonstrates differences between experienced and less experienced surgeons. This method could be used to audit practice and observe effects of changes to technique.

Development and validation of a risk score to predict the overall survival following surgical resection of hepatocellular carcinoma in non-cirrhotic liver.

BACKGROUND: The aim of this study was to develop and validate a risk score to predict overall survival (OS) in patients undergoing surgical resection for hepatocellular carcinoma in non-cirrhotic liver (NC-HCC). METHODS: Patients who underwent resection for NC-HCC between 2004 and 2013 were identified from the SEER database. A derivation set of 75% of this cohort was used to develop a risk score. This was then internally validated on the remaining patients, and externally validated using a cohort of patients from The HPB Unit, Birmingham, UK. RESULTS: A total of 3897 patients were included from the SEER database, with a median post-diagnosis survival of 59 months. In the derivation set, multivariable analyses identified male sex, increasing tumour size, the presence of multiple tumours, bilobar tumours and major vascular invasion as adverse prognostic factors. A risk score generated from these factors was significantly predictive of OS, and was used to classify patients into low, medium and high-risk groups. These groups had a five-year OS of 69%, 51% and 19% in the internal, and 73%, 50% and 45% in the external validation sets. CONCLUSION: The proposed risk score is useful in the selection, pre-operative consenting and counselling of patients for surgery and to allow patients to make an informed decision regarding treatment.

Retrieval Practice or Overall Donor and Recipient Risk: What Impacts on Outcomes After Donation After Circulatory Death Liver Transplantation in the United Kingdom?

Parameters of retrieval surgery are meticulously documented in the United Kingdom, where up to 40% of livers are donation after circulatory death (DCD) donations. This retrospective analysis focuses on outcomes after transplantation of DCD livers, retrieved by different UK centers between 2011 and 2016. Donor and recipient risk factors and the donor retrieval technique were assessed. A total of 236 DCD livers from 9 retrieval centers with a median UK DCD risk score of 5 (low risk) to 7 points (high risk) were compared. The majority used University of Wisconsin solution for aortic flush with a median hepatectomy time of 27-44 minutes. The overall liver injury rate appeared relatively high (27.1%) with an observed tendency toward more retrieval injuries from centers performing a quicker hepatectomy. Among all included risk factors, the UK DCD risk score remained the best predictor for overall graft loss in the multivariate analysis (P < 0.001). In high-risk and futile donor-recipient combinations, the occurrence of liver retrieval injuries had negative impact on graft survival (P = 0.023). Expectedly, more ischemic cholangiopathies (P = 0.003) were found in livers transplanted with a higher cumulative donor-recipient risk. Although more biliary complications with subsequent graft loss were found in high-risk donor-recipient combinations, the impact of the standardized national retrieval practice on outcomes after DCD liver transplantation was minimal.

Developing and validating a preoperative risk score to predict 90-day mortality after liver resection.

BACKGROUND: Hepatobiliary surgeons continue to expand the pool of patients undergoing liver resection using combinations of surgical and interventional procedures with chemotherapy. Improved perioperative care allows for operation on higher risk surgical patients. Postoperative outcomes, including 90-day mortality that improved over the past decade but still varies across cohorts. This study developed a preoperative risk score, on the basis significant clinical and laboratory variables, to predict 90-day mortality after hepatectomy. METHODS: All patients who underwent hepatectomy between 2011 and 2016 were included. Univariable and multivariable analyses were performed to identify the predictors of postoperative mortality and a risk score was derived and validated. RESULTS: The overall 90-day mortality rate in the derivation cohort (n = 1269 patients) was 4.0% (N = 51). Increasing patient age (P < 0.001), extent of resection (P = 0.001), diabetes mellitus (P = 0.006), and low preoperative sodium (P = 0.012) were predictors of the increased 90-day mortality in the multivariable analysis. The risk model developed based on these factors had an AUROC of 0.778 (P < 0.001) and remained significant in a validation cohort of 788 patients (AUROC: 0.703, P < 0.001). CONCLUSION: The proposed preoperative risk score to predict 90-day mortality after liver resection could be useful for appropriate counseling, optimization, and risk-adjusted assessment of surgical outcomes.

Human immunodeficiency virus-infected liver transplant recipients with incidental hepatocellular carcinoma: A prospective multicenter nationwide cohort study.

There is a lack of data on incidental hepatocellular carcinoma (iHCC) in the setting of liver transplantation (LT) in human immunodeficiency virus (HIV)-infected patients. This study aims to describe the frequency, histopathological characteristics, and outcomes of HIV+ LT recipients with iHCC from a Spanish multicenter cohort in comparison with a matched cohort of LT patients without HIV infection. A total of 15 (6%) out of 271 patients with HIV infection who received LT in Spain from 2002 to 2012 and 38 (5%) out of the 811 HIV- counterparts presented iHCC in liver explants (P = 0.58). Patients with iHCC constitute the present study population. All patients also had hepatitis C virus (HCV)-related cirrhosis. There were no significant differences in histopathological features of iHCC between the 2 groups. Most patients showed a small number and size of tumoral nodules, and few patients had satellite nodules, microvascular invasion, or poorly differentiated tumors. After a median follow-up of 49 months, no patient developed hepatocellular carcinoma (HCC) recurrence after LT. HIV+ LT recipients tended to have lower survival than their HIV- counterparts at 1 (73% versus 92%), 3 (67% versus 84%), and 5 years (50% versus 80%; P = 0.06). There was also a trend to a higher frequency of HCV recurrence as a cause of death in the former (33% versus 10%; P = 0.097). In conclusion, among LT recipients for HCV-related cirrhosis, the incidence and histopathological features of iHCC in HIV+ and HIV- patients were similar. However, post-LT survival was lower in HIV+ patients probably because of a more aggressive HCV recurrence. Liver Transplantation 23 645-651 2017 AASLD.

Human immunodeficiency virus infection does not worsen prognosis of liver transplantation for hepatocellular carcinoma.

UNLABELLED: The impact of human immunodeficiency virus (HIV) infection on patients undergoing liver transplantation (LT) for hepatocellular carcinoma (HCC) is uncertain. This study aimed to assess the outcome of a prospective Spanish nationwide cohort of HIV-infected patients undergoing LT for HCC (2002-2014). These patients were matched (age, gender, year of LT, center, and hepatitis C virus (HCV) or hepatitis B virus infection) with non-HIV-infected controls (1:3 ratio). Patients with incidental HCC were excluded. Seventy-four HIV-infected patients and 222 non-HIV-infected patients were included. All patients had cirrhosis, mostly due to HCV infection (92%). HIV-infected patients were younger (47 versus 51 years) and had undetectable HCV RNA at LT (19% versus 9%) more frequently than non-HIV-infected patients. No significant differences were detected between HIV-infected and non-HIV-infected recipients in the radiological characteristics of HCC at enlisting or in the histopathological findings for HCC in the explanted liver. Survival at 1, 3, and 5 years for HIV-infected versus non-HIV-infected patients was 88% versus 90%, 78% versus 78%, and 67% versus 73% (P = 0.779), respectively. HCV infection (hazard ratio = 7.90, 95% confidence interval 1.07-56.82) and maximum nodule diameter >3 cm in the explanted liver (hazard ratio = 1.72, 95% confidence interval 1.02-2.89) were independently associated with mortality in the whole series. HCC recurred in 12 HIV-infected patients (16%) and 32 non-HIV-infected patients (14%), with a probability of 4% versus 5% at 1 year, 18% versus 12% at 3 years, and 20% versus 19% at 5 years (P = 0.904). Microscopic vascular invasion (hazard ratio = 3.40, 95% confidence interval 1.34-8.64) was the only factor independently associated with HCC recurrence. CONCLUSIONS: HIV infection had no impact on recurrence of HCC or survival after LT. Our results support the indication of LT in HIV-infected patients with HCC.

A reduced time to surgery within a 'fast track' pathway for periampullary malignancy is associated with an increased rate of pancreatoduodenectomy.

INTRODUCTION: Pancreatoduodenectomy (PD) typically follows preoperative biliary drainage (PBD) despite PBD being potentially harmful. This study evaluated a pathway to avoid PBD within the framework of the UK's NHS. METHOD: A prospective observational study of jaundiced patients undergoing PD for periampullary cancer. A pathway to provide early surgery without PBD was introduced at the start of the study period. RESULTS: Over 12 months 61 and 32 patients underwent surgery with and without PBD respectively; 95% of patients in the PBD group had been stented before referral. The time from CT scan to surgery was shorter in the no PBD group (16 vs 65 days, p < 0.0001). Significantly more patients underwent PD in the no PBD group (31/32 vs 46/61, p = 0.009) and venous resection (10/31 vs 4/46, p = 0.014). The sensitivity of initial CT scan to define borderline resectable disease was worse in the PBD group (91 vs 50%, p = 0.042). CONCLUSIONS: Early surgery to avoid PBD is possible within the NHS. By reducing the time to surgery it appears that more patients undergo potentially curative resection. It is desirable to understand why surgery without PBD is not performed routinely as are the development of strategies to support its more widespread practice.

Pegylated interferon plus ribavirin in HIV-infected patients with recurrent hepatitis C after liver transplantation: a prospective cohort study.

BACKGROUND & AIMS: The aim of this study was to evaluate the results of treatment with pegylated interferon and ribavirin for the recurrence of hepatitis C after liver transplantation in HCV/HIV-coinfected patients. METHODS: This was a prospective, multicentre cohort study, including 78 HCV/HIV-coinfected liver transplant patients who received treatment for recurrent hepatitis C. For comparison, we included 176 matched HCV-monoinfected patients who underwent liver transplantation during the same period of time at the same centres and were treated for recurrent hepatitis C. RESULTS: Antiviral therapy was discontinued prematurely in 56% and 39% (p = 0.016), mainly because of toxicity (22% and 11%, respectively; p=0.034). Sustained virological response (SVR) was achieved in 21% of the coinfected patients and in 36% of monoinfected patients (p = 0.013). For genotype 1, SVR rates were 10% and 33% (p = 0.002), respectively; no significant differences were observed for the other genotypes. A multivariate analysis based on the whole series identified HIV-coinfection as an independent predictor of lack of SVR (OR, 0.17; 95% CI, 0.06-0.42). Other predictors of SVR were donor age, pretreatment HCV viral load, HCV genotype, and early virological response. SVR was associated with a significant improvement in survival: 5-year survival after antiviral treatment was 79% for HCV/HIV-coinfected patients with SVR vs. 43% for those without (p = 0.02) and 92% vs. 60% in HCV-monoinfected patients (p < 0.001), respectively. CONCLUSIONS: The response to pegylated interferon and ribavirin was poorer in HCV/HIV-coinfected liver recipients, particularly those with genotype 1. However, when SVR was achieved, survival of coinfected patients increased significantly.

[IV Consensus meeting of the Spanish Society of Liver Transplantation (SETH) 2012. Liver transplant with non-conventional grafts: Split liver transplantation and non-heart beating donors]. / IV Reunión de consenso de la Sociedad Española de Trasplante Hepático (SETH) 2012. Trasplante hepático con injertos no convencionales: bipartición hepática (split) y donante en asistolia.

The disbalance between the number of candidates to liver transplant and the number of liver grafts leads to waiting list mortality. Two potential ways of increasing the number of liver grafts are split liver transplantation and the transplantation of grafts from non-heart beating donors. Both of them were discussed in a consensus meeting of the Spanish Society of Liver Transplantation in October 2012. This paper outlines the conclusions of that meeting.

Potential clinical utility of intraoperative fluid amylase measurement during pancreaticoduodenectomy.

Backgrounds/Aims: Postoperative pancreatic fistula (POPF) after pancreaticoduodenectomy (PD) is a source of major morbidity and mortality. Early diagnosis and treatment of POPF is mandatory to improve patient outcomes and clinical risk scores may be ombined with postoperative drain fluid amylase (DFA) values to stratify patients. The aim of this pilot study was to etermine if intraoperative fluid amylase (IFA) values correlate with DFA1 and POPF. Methods: In patients undergoing PD from February to November 2020, intraoperative samples of intra-abdominal fluid adjacent to the pancreatic anastomosis were taken and sent for fluid amylase measurement prior to abdominal closure. Data regarding patient demographics, postoperative DFA values, complications, and mortality were prospectively collected. Results: Data were obtained for 52 patients with a median alternative Fistula Risk Score (aFRS) of 9.9. Postoperative complications occurred in 20 (38.5%) patients (five Clavien grade ≥ 3). There were eight POPFs and two patients died (pneumonia/sepsis). There was a significant correlation between IFA and DFA1 (R2 = 0.713; p < 0.001) and DFA3 (p < 0.001), and the median IFA was higher in patients with POPF than patients without (1,232.5 vs. 122; p = 0.0003). IFA > 260 U/L predicted POPF with sensitivity, specificity, positive and negative predictive values of 88.0%, 75.0%, 39.0%, and 97.0%, respectively. The incidence of POPF was 43.0% in high-risk (high aFRS/IFA) and 0% in lowrisk patients (low aFRS/IFA). Conclusions: IFA correlated with POPF and may be a useful adjunct to clinical risk scores to stratify patients during PD. Larger, prospective studies are needed to determine whether IFA has clinical utility.

Epidemiology and outcome of infections in human immunodeficiency virus/hepatitis C virus-coinfected liver transplant recipients: a FIPSE/GESIDA prospective cohort study.

Information about infections unrelated to acquired immunodeficiency syndrome (AIDS) in human immunodeficiency virus (HIV)-infected liver recipients is scarce. The aims of this study were to describe the prevalence, clinical characteristics, time of onset, and outcomes of bacterial, viral, and fungal infections in HIV/hepatitis C virus (HCV)-coinfected orthotopic liver transplant recipients and to identify risk factors for developing severe infections. We studied 84 consecutive HIV/HCV-coinfected patients who underwent liver transplantation at 17 sites in Spain between 2002 and 2006 and were followed until December 2009. The median age was 42 years, and 76% were men. The median follow-up was 2.6 years (interquartile range = 1.25-3.53 years), and 54 recipients (64%) developed at least 1 infection. Thirty-eight (45%) patients had bacterial infections, 21 (25%) had cytomegalovirus (CMV) infections (2 had CMV disease), 13 (15%) had herpes simplex virus infections, and 16 (19%) had fungal infections (7 cases were invasive). Nine patients (11%) developed 10 opportunistic infections with a 44% mortality rate. Forty-three of 119 infectious episodes (36%) occurred in the first month after transplantation, and 53 (45%) occurred after the sixth month. Thirty-six patients (43%) had severe infections. Overall, 36 patients (43%) died, and the deaths were related to severe infections in 7 cases (19%). Severe infections increased the mortality rate almost 3-fold [hazard ratio (HR) = 2.9, 95% confidence interval (CI) = 1.5-5.8]. Independent factors for severe infections included a pretransplant Model for End-Stage Liver Disease (MELD) score >15 (HR = 3.5, 95% CI = 1.70-7.1), a history of AIDS-defining events before transplantation (HR = 4.0, 95% CI = 1.9-8.6), and non-tacrolimus-based immunosuppression (HR = 2.5, 95% CI = 1.3-4.8). In conclusion, the rates of severe and opportunistic infections are high in HIV/HCV-coinfected liver recipients and especially in those with a history of AIDS, a high MELD score, or non-tacrolimus-based immunosuppression.

Incidental gallbladder cancer diagnosis confers survival advantage irrespective of tumour stage and characteristics.

BACKGROUND: Incidental gallbladder cancer (IGBC) represents 50%-60% of gallbladder cancer cases. Data are conflicting on the role of IGBC diagnosis in oncological outcomes. Some studies suggest that IGBC diagnosis does not affect outcomes, while others that overall survival (OS) is longer in these cases compared to non-incidental diagnosis (NIGBC). Furthermore, some studies reported early tumour stages and histopathologic characteristics as possible confounders, while others not. AIM: To investigate the role of IGBC diagnosis on patients' overall survival, especially after surgical treatment with curative intent. METHODS: Retrospective analysis of all patient referrals with gallbladder cancer between 2008 and 2020 in a tertiary hepatobiliary centre. Statistical comparison of patient and tumour characteristics between IGBC and NIGBC subgroups was performed. Survival analysis for the whole cohort, surgical and non-surgical subgroups was done with the Kaplan-Meier method and the use of log rank test. Risk analysis was performed with univariable and multivariable Cox regression analysis. RESULTS: The cohort included 261 patients with gallbladder cancer. 65% of cases had NIGBC and 35% had IGBC. A total of 90 patients received surgical treatment (66% of IGBC cases and 19% of NIGBC cases). NIGBC patients had more advanced T stage and required more extensive resections than IGBC ones. OS was longer in patients with IGBC in the whole cohort (29 vs 4 mo, P < 0.001), as well as in the non-surgical (14 vs 2 mo, P < 0.001) and surgical subgroups (29 vs 16.5 mo, P = 0.001). Disease free survival (DFS) after surgery was longer in patients with IGBC (21.5 mo vs 8.5 mo, P = 0.007). N stage and resection margin status were identified as independent predictors of OS and DFS. NIGBC diagnosis was identified as an independent predictor of OS. CONCLUSION: IGBC diagnosis may confer a survival advantage independently of the pathological stage and tumour characteristics. Prospective studies are required to further investigate this, including detailed pathological analysis and molecular gene expression.

Management of Ascites Following Deceased Donor Liver Transplantation: A Case Series.

Background: Persistent ascites after orthotropic liver transplantation has numerous causes and can be challenging to manage. This study aimed to determine the outcomes associated with conservative and endovascular intervention of posttransplant ascites after deceased donor liver transplantation. Methods: Adult (≥18 y) liver transplant recipients (between 2006 and 2019) who underwent hepatic venous pressure studies to investigate posttransplant ascites were included in this retrospective study. Comparisons were made between those who were managed with conservative therapy versus endovascular intervention and were also based on hepatic venous wedge pressure gradient (normal [≤10 mm Hg] versus elevated [>10 mm Hg]). Results: A total of 30 patients underwent hepatic venography to investigate ascites during the study period. The median time from transplant to venography was 70 d. At least 1 endovascular intervention was performed in 18 of 30 patients (62%), and 12 of 30 patients (38%) were managed conservatively. Endovascular interventions included angioplasty (n = 4), hepatic vein stenting (n = 9), or a transjugular intrahepatic portosystemic shunt (n = 7). The mean (range) hepatic venous wedge pressure gradient for the conservative and endovascular intervention groups was 12 mm Hg (3-23) and14 mm Hg (2-35), respectively. At a 6-mo follow-up, ascites resolved in 6 of 12 patients (50%) and 11 of 18 patients (61%) in the medical management and endovascular groups, respectively. The graft survival rates at 6 and 12 mo were (7/12 [58%] versus 17/18 [94%], P = 0.02) and (7/12 [58%] versus 14/18 [78%], P = 0.25), respectively. Conclusions: Despite medical or endovascular intervention, resolution of ascites is achieved in <60% of patients with persistent ascites. Biopsy findings and venographic pressure studies should be carefully integrated into the management of posttransplant ascites.

Switching to sirolimus monotherapy for de novo tumors after liver transplantation. A preliminary experience.

BACKGROUND/AIMS: Alcoholic cirrhosis, smoking, and use of calcineurin inhibitors (CNI) are associated with the development of de novo tumors in liver transplant (LT) recipients. Sirolimus is an immunosuppressor with antitumoral properties. METHODOLOGY: Between April 1986 and April 2007, we performed 1231 liver transplants in 1084 recipients. A total of 128 de novo tumors were observed in 116 recipients from a sample of 850 adult recipients who survived more than 2 months. This study comprises 16 LT recipients (13 male and 3 female; mean age, 45.1 +/- 11.1 years) who were switched to sirolimus monotherapy who developed de novo tumors and were switched from CNI or mycophenolate mofetil to sirolimus monotherapy. RESULTS: De novo tumors location: 2 lymphomas, 9 upper aerodigestive, 1 skin, 1 parotid, 1 lung, 1 breast, and 1 rectum. Time from LT to sirolimus monotherapy was 86 months; time taking to switching from CNI to sirolimus monotherapy was 48 days, and mean follow-up of patients on sirolimus monotherapy was 15.7 months. Thirteen patients underwent tumor resection, 5 received chemotherapy, and 5 received radiotherapy. Five patients died during the follow-up, and patient survival after diagnosis was 42.8 months. Mean dose of sirolimus was 2.7 mg/day and the mean trough level was 8.9 ng/mL. Total cholesterol and triglycerides values increased after switching. Mean serum creatinine, glucose, AST and ALT values, and haematological parameters were similar before and after switching. No patients developed acute rejection, and adverse effects were observed in 8 patients. CONCLUSIONS: Sirolimus monotherapy can be used safely to improve survival in LT recipients with de novo tumors.