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BACKGROUND The persisting organ shortage in the field of transplantation recommends the use of marginal kidneys which poorly tolerate ischemic damage. Adenosine triphosphate (ATP) depletion during cold ischemia time (CIT) is considered crucial for graft function. We tested different strategies of kidney perfusion before transplantation in the attempt to improve the technique. MATERIAL AND METHODS Twenty human discarded kidneys from donors after brain death and with at least 20 hours of CIT were randomized to the following experimental groups (treatment time three-hours at 4°C): a) static cold storage (CS); b) static cold hyperbaric oxygenation (Hyp); c) hypothermic perfusion (PE); d) hypothermic perfusion in hyperbaric oxygenation (PE-Hyp); and e) hypothermic oxygenated perfusion (PE-O2). RESULTS Histological results showed that perfusion with or without oxygen did not produce any endothelial damage. A depletion of ATP content following the preservation procedure was observed in CS, PE, and Hyp, while PE-Hyp and PE-O2 were associated with a net increase of ATP content with respect to baseline level. In addition, PE-Hyp was associated with a significant downregulation of endothelial isoform of nitric oxide synthase (eNOS) gene expression and of hypoxia inducible factor-1α (HIF-1α). CONCLUSIONS Hyperbaric or normobaric oxygenation with perfusion improves organ metabolic preservation compared to other methods. This approach may prevent the onset of delayed graft function, but clinical trials are needed to confirm this.

Background: Increased expertise with minimally invasive liver surgery (MILS) could cause an unjustified extension of indications to resect liver benign disease (BD). The aim of this study was to evaluate the operative risk of MILS for BD and if implementation and diffusion of MILS have widened indications for BD resection. Methods: A prospective study including centers with > 6 MILS for BD, enrolled in the I Go MILS registry from January 2015 to October 2016. Cysts fenestrations were excluded. Results: Eight hundred eighteen MILS were performed in 15 centers. One hundred seventy-three of these (21.1%) were for BD: conversion rate was 6.9%, postoperative mortality and morbidity rates were 0 and 13.9%. During the same period, 3713 liver resections (open + MILS) were performed and 407 (11.0%) were for BD. A time-trend analysis showed that the total number of MILS and the number of MILS for malignant disease significantly increased, but this increasing trend was not documented for the number of MILS for BD, which remained stable during the study period of time. This trend was confirmed for the overall rate of resected BD (open + MILS) that remained stable. Discussion: BD represents a valid indication for MILS. For BD, 21.1% of MILS was performed, rate significantly lower than that previously reported in Italy. Although an evident growth of the use of MILS was observed during the time period analysis in Italy, this trend did not correspond to an increased number of MILS for BD, and the overall rate of resected BD was comparable to that reported in previous large open series.

Liver transplantation (LT) represents the only chance of long-term survival for patients with end-stage liver disease. When the mortality rate for transplant patients returns to the same level as that for the general population, they can be considered statistically cured. However, cure models in the setting of LT have never been applied. Data from 1371 adult patients undergoing LT for the first time between January 1999 and December 2012 at 2 Italian centers were reviewed in order to establish probabilities of being cured by LT. A parametric Weibull model was applied to compare the mortality rate after LT to the rate expected for the general population (matched by sex and age). The observed 3-, 5-, and 10-year overall survival rates after LT were 77.8%, 73.3%, and 65.6%, respectively, and they did not differ between the 2 centers (P = 0.37). The cure fraction for the entire study population was 63.4% (95% confidence interval = 52.6%-72.0%), and the time to cure was 10 years with a 90% confidence level. The best cure fraction was observed for younger recipients without hepatitis C virus (HCV) who had favorable donor-recipient matches, that is, low Donor Model for End-Stage Liver Disease (D-MELD) scores (90.1%); conversely, the lowest probability was observed for elderly HCV recipients with high D-MELD scores (34.6%). The time to cure was 6.22 years for non-HCV patients and 14.78 years for HCV patients. The median survival time for uncured patients was 2.29 years. Among uncured recipients, the longest survival time was observed for younger patients (7.31 years). In conclusion, we provide here a new clinical measure for LT suggesting that survival after transplantation can approximate that of the general population and provide a statistical cure.

INTRODUCTION: Hepatocellular carcinoma (HCC) is an established indication for liver transplantation (LT), but the selection criteria and priority are still debated. AIMS: To ascertain the number and features of patients with HCC who undergo transplantation in a Western country, the number of patients eligible for LT according to the American Association for the Study of Liver Diseases (AASLD) guidelines, the number of patients who actually undergo transplantation and whether adherence affects survival. METHODS: This is a retrospective analysis from a multicentre Italian database of 2042 cases of HCC, recruited prospectively and consecutively. Kaplan-Meier (log rank) and Cox multivariate analysis estimated survival. RESULTS: Patients who had undergone transplantation (50, 2.5%, with no change over time) had a median survival of 133 months, significantly influenced by the number of lesions and alpha-fetoprotein levels, which were found to be independent predictors of survival on multivariate analysis. Milan criteria were fulfilled in 68%, impacting on survival, whereas 48% fulfilled AASLD guidelines, without such an impact. Two hundred and twenty-eight (11%) patients were eligible for LT according to AASLD; in this group, alpha-fetoprotein levels and Child-Pugh class were independent predictors of survival. CONCLUSION: Among patients with HCC, those undergoing LT represent a small minority; even fewer (1%) are those who undergo transplantation according to AASLD guidelines, adherence to which only marginally affects survival. Overall, LT impact on HCC patients' treatment is very limited

Post-reperfusion syndrome (PRS) during isolated intestinal Background: transplantation (ITx) is characterized by decreased systemic blood pressure, systemic vascular resistance, and cardiac output and by a moderate increased pulmonary arterial pressure. We hypothesize that the more severe PRS causes a poorer long-term outcome. The primary aim of this study was to determine the independent clinical predictors of intra-operative PRS, as well as to investigate the link between the severity of PRS and the intra-operative profiles and to examine the post-operative complications and their relationship This observational study was conducted on 27 with transplant outcome. Methods: patients undergoing isolated ITx in a single adult liver and multivisceral transplantation center. PRS was considered when the mean arterial blood pressure min was 30% lower than the pre-unclamping value and lasted for at least one The main results of min after unclamping. Results and conclusions: within 10 this study can be summarized in two findings: in patients undergoing ITx, the duration of cold ischemia and the pre-operative glomerular filtration rate were independent predictors of PRS and the occurrence of intra-operative PRS was associated with significantly more frequent post-operative renal failure and early post-operative death.

The efficacy and safety of dual-therapy regimens of twice-daily tacrolimus (BID; Prograf) and once-daily tacrolimus (QD; Advagraf) administered with steroids, without antibody induction, were compared in a multicenter, 1:1-randomized, two-arm, parallel-group study in 475 primary liver transplant recipients. A double-blind, double-dummy 24-week period was followed by an open extension to 12 months posttransplant. The primary endpoint, event rate of biopsy-proven acute rejection (BPAR) at 24 weeks, was 33.7% for tacrolimus BID versus 36.3% for tacrolimus QD (Per-protocol set; p = 0.512; treatment difference 2.6%, 95% confidence interval -7.3%, 12.4%), falling within the predefined 15% noninferiority margin. At 12 months, BPAR episodes requiring treatment were similar for tacrolimus BID and QD (28.1% and 24.7%). Twelve-month patient and graft survival was 90.8% and 85.6% for tacrolimus BID and 89.2% and 85.3% for tacrolimus QD. Adverse event (AE) profiles were similar for both tacrolimus BID and QD with comparable incidences of AEs and serious AEs. Tacrolimus QD was well tolerated with similar efficacy and safety profiles to tacrolimus BID.

Infections continue to be one of the leading causes of morbidity and mortality in liver transplant recipients. We retrospectively reviewed the symptomatic infectious episodes that occurred during the first year post-transplant to determine time of onset, causative pathogens and cell-mediated immunity response patterns. Ninety-eight of the 202 (48.5%) recipients enrolled developed at least one infectious episode. The total number of infectious episodes was 135: 77 (57.1%) bacterial, 45 (33.3%) viral and 13 (9.6%) fungal. The most frequently isolated bacteria were Escherichia coli (21 isolates) and Klebsiella pneumoniae (19 isolates). Overall, extended-spectrum beta lactamase-producing and methicillin-resistant organisms were responsible for 29 (29/77; 37.7%) infectious episodes. Members of the herpes virus group, in particular cytomegalovirus (34/45 viral infections, 75.5%), were detected. Candida species (9 isolates) followed by Aspergillus species (4 isolates) were isolated. The majority of infections (63%) occurred during the early post-transplant phase (

Objective: Laparoscopic liver resection (LLR) for Hepatocellular Carcinoma (HCC) is one of the most important indications for the minimally invasive approach. Our study aims to analyze the experience of the Italian Group of Minimally Invasive Liver Surgery with laparoscopic surgical treatment of HCC, with a focus on tumor location and how it affects morbidity and mortality. Methods: 38 centers participated in this study; 372 cases of LLR for HCC were prospectively enrolled. Patients were divided into two groups according to the HCC nodule location. Group 1 favorable location and group 2 unfavorable location. Perioperative outcomes were compared between the two groups before and after a propensity score match (PS) 1:1. Results: Before PS in group 2 surgical time was longer; conversion rate was higher; postoperative transfusion and comprehensive complication index were also higher. PS was performed with a cohort of 298 patients (from 18 centers), with 66 and 232 patients with HCC in unfavorable and favorable locations, respectively. After PS matching, 62 patients from group 1 and group 2 each were compared. Operative and postoperative course were similar in patients with HCC in favorable and unfavorable LLR locations. Surgical margins were found to be identical before and after PS. Conclusions: These results show that LLR in patients with HCC can be safely performed in all segments because of the extensive experience of all surgeons from multiple centers in performing traditional open liver surgery as well as laparoscopic surgery.

Liver transplantation is the ideal treatment for patients affected by early stage hepatocellular carcinoma and chronic liver disease. Considering organs shortage, alternative treatments have to be adopted to minimize the waitlist drop-out, and in case of recurrence within the accepted criteria, salvage transplantation can be considered. Surgical resection is one of the most effective treatments, with the possibility of oncological radicality and pathological analysis of the specimen. Although these theoretical advantages, surgical strategy cannot be applied to all patients because of the impaired liver function as well as the amount of parenchyma to be resected does not allow a sufficient future liver remnant. Furthermore, resection by laparotomy may lead to strong intra-abdominal adhesions in a contest of portal hypertension and, as potential consequence, increase transplantation difficulty raising morbidity. Laparoscopic liver resection is now performed as a routine procedure in tertiary referral centers, with increasing evidence of long-term results comparable to traditional surgery together with the advantages of a minimally invasive approach. In addition, with a salvage transplantation strategy that has been shown to be comparable to primary transplantation, the patient can live with his native liver avoiding an invasive procedure and long-term immunosuppression, allowing the use of liver grafts for the community. We present the results of an Italian multicenter experience of salvage liver transplantation following the recurrence of HCC initially treated by laparoscopic resection in 31 patients, performed by four referral centers. Mean operative transplantation time was 450min, morbidity was 41.9%, 90-days mortality was 3.2%, and median post-operative length of stay was 17.9days. Salvage liver transplantation after laparoscopic liver resection for HCC is comparable to open surgery in terms of operative time, oncologic radicality, morbidity and mortality, with the advantages of laparoscopic surgery.

Background Data about the optimal management of immunosuppressive therapy in liver transplant (LT) recipients with bloodstream infection (BSI) are missing. We aimed to describe the management of immunosuppressive therapy at diagnosis of BSI in LT recipients and to assess its impact on 28-day mortality. Methods We performed a single-center retrospective study of all LT recipients diagnosed with BSI, over 10-year period. Multivariate Cox regression analysis of risk factors for all cause 28-day mortality was adjusted for the propensity score of being managed with "any reduction" in immunosuppressive therapy at the diagnosis of BSI. Results We identified 209 episodes of BSI in 157 LT recipients: 107 (68%) male, median age 54 (IQR 48-63) years. "Any reduction" was made in 90 (43%) cases including: dosage reduction of ≥1 immunosuppressive drug in 31 (15%), discontinuation of ≥1 immunosuppressive drug in 28 (13%), both dosage reduction and discontinuation in 13 (6%), complete withdrawal of immunosuppressive therapy in 18 (9%) cases. All-cause 28-day mortality rate was 13.4%, varying from 22% to 7% (P = .002) in cases with and without "any reduction". Cox regression showed septic shock (aHR 3.15, P = .007) and "any reduction" (aHR 2.50, P = .02) as independent risk factors for all-cause 28-day mortality, while Escherichia coli (aHR 0.38, P = .03) and source control (aHR 0.43, P = .04) were protective factors. The final model did not change after the introduction of the propensity score for "any reduction". Conclusions Any reduction in the immunosuppressive therapy was common and was associated with worse outcome in LT recipients developing BSI.

Background We performed serological and molecular pretransplant screening in solid organ transplant (SOT) donors and recipients in north central Italy and a surveillance program for human herpesvirus 8 (HHV8) infection after transplant, aiming to establish an optimal management of HHV8 infection in SOT recipients. Methods For pretransplant HHV8 screening in both donors and recipients, 6 serological (4 indirect immunofluorescent assays [IFA] and 2 enzyme-linked immunosorbent assays-both HHV8 lytic and latent antigen based) and 2 molecular assays were used. A reference standard to identify HHV8-positive patients was defined by at least 2 positive assays. All transplant patients at risk to develop HHV8-related disease underwent virological posttransplant monitoring by quantitative real-time polymerase chain reaction (PCR) assay. Results Human herpesvirus 8 seroprevalence was 4% (10/249) in donors and 18% (93/517) in organ recipients. The best performance was obtained by 2 lytic antigen-based IFAs that showed almost perfect agreement to the reference standard (0.943 and 0.931 Cohen kappa). Human herpesvirus 8-DNA was detected in 6.8% and 2.9% of HHV8-seropositive donor samples by in-house nested PCR and quantitative real-time PCR assays, respectively. After transplant, 3 (25%) of 12 HHV8-mismatch patients (seropositive donor/seronegative recipient) developed a primary infection, one of whom developed a lethal nonmalignant illness. Two of 93 HHV8-seropositive recipients (2.1%) had viral replication in posttransplant period, one of whom developed Kaposi sarcoma. Conclusions Serological assays, specifically lytic IFAs, were the best methodological approach to identify HHV8-infected SOT donors and recipients. A very low incidence (1.9%) of posttransplant HHV8-related disease was observed.

One of the main problems in transplant surgery is the preservation of the organ during the cold ischemic time. The interrupted blood supply triggers a cascade of biological modifications resulting in cell death, which predisposes to discharge of a large quantity of toxic metabolites at the moment of organ reperfusion. Many approaches have been studied to prevent the toxic processes. Immediately after procurement, kidneys are flushed with these solutions. Two main: techniques of organ preservation are cold static storage and hypothermic machine perfusion (HMP). Based on age and comorbidities, individuals can be generally divided into 2 groups: ideal and marginal donors. Characteristics of organs from marginal donors are associated with an increased rate of delayed graft function and primary graft nonfunction (PNF), which reduce transplant survival and increase the acute rejection risk. In the last 20 years, the United Network of Organ Sharing has reported a 170% increase in deceased donors older than 50 years of age. Techniques of perfusion have been demonstrated to play a pivotal role in graft function after transplantation. Some studies suggest that HMP may improve outcomes after transplantation.

BACKGROUND & AIMS: Both hepatic resection and radiofrequency ablation (RFA) are considered curative treatments for hepatocellular carcinoma (HCC), but their economic impact still remains not determined. Aim of the present study was to analyze the cost-effectiveness (CE) of these two strategies in early stage HCC (Milan criteria). METHODS: As first step, a meta-analysis of the pertinent literature of the last decade was performed. Seventeen studies fulfilled the inclusion criteria: 3,996 patients underwent resection and 4,424 underwent RFA for early HCC. Data obtained from the meta-analysis were used to construct a Markov model. Costs were assessed from the health care providers perspective. A Monte-Carlo probabilistic sensitivity analysis was used to estimate outcomes with distribution samples of 1,000 patients for each treatment arm. RESULTS: In a 10 year perspective, for very early HCC (single nodule

Background/Aims: The shortage in organ supply has required the use of expanded criteria donors (ECD) for kidney transplantation. Current pre-transplant evaluations of ECD organs are based on histological, clinical or mixed criteria. This monocentric study investigates the predictivity of Karpinski’s histological score on 3-year graft function in renal transplant. Ex-post classification using Nyberg’s score was carried out to assess the reliability of a purely clinical score and its applicability for organ allocation. Methods: We evaluated 407 deceased donors (251 optimal and 156 ECD) for renal transplants performed between 2001 and 2006. The differences in creatinine levels and MDRD-GFR at transplant and 1, 2 and 3 years post-transplant between optimal donors and ECD were recorded. Amongst ECD organs, the effect of different Karpinski score classes (0–1, 2, 3, 4, double transplants) on 3-year graft outcomes was analyzed. We then compared renal function over time across the Nyberg grades (A, B, C, and D). Results: Karpinski scores 0–1 and 2 and double transplants were associated with improved graft function compared to scores 3 and 4. Nyberg’s clinical score shows a good fit with medium-term outcome and Karpinski’s score, but among the donors with a high Nyberg grade (C and D), it fails to differentiate between allocable or non-allocable organs (due to Karpinski’s score ≥7). Conclusions: Our data demonstrate a correlation of histological damage at the time of transplant with 3-year graft function, but at present we are unable to provide any supposition on the possible outcome of the discarded kidneys.

Importance The prognostic value of lymph node (LN) assessment after liver resection for hilar cholangiocarcinoma (HC) is still controversial, and the number of LNs required to be removed to obtain adequate staging is not well defined. Objectives To evaluate the LN status in patients after liver resection for HC and to clarify which prognostic factor (the number of positive LNs or the LN ratio [LNR]) was most accurate for staging and what minimum number of retrieved LNs was required for adequate staging. Design, Setting, and Participants Retrospective multicenter study of patients who underwent resection for HC between January 1, 1992, and December 31, 2007, at 8 hepatobiliary Italian centers. The last follow-up was assessed in July 2014. Main Outcome and Measures Differences in overall survival (OS) according to the LN status were analyzed. The OS results were defined as actual because all included patients completed a 5-year follow-up. Results One-hundred seventy-five patients with 1133 retrieved LNs were analyzed. The mean (SD) age of the cohort was 63 (10) years, and 42.9% (75 of 175) were female. The median number of LNs examined per patient was 6.5. Forty percent (70 of 175) had LN metastasis. An LNR exceeding 0.20 was associated with significantly lower 5-year OS than an LNR of 0.20 or less (10.6% vs 24.4%; odds ratio, 2.434; 95% CI, 1.020-5.810; P = .04). On multivariable analysis, the LNR was the only independent prognostic factor for OS but was influenced by the total number of retrieved LNs. The LNR was greater than 0.20 in all patients (30 of 30) with 1 to 4 retrieved LNs and in 52.5% (21 of 40) of patients with at least 5 retrieved LNs. Five-year OS in patients with 1 to 5 retrieved LNs was significantly lower than that in those with 6 to 7 retrieved LNs and those with at least 8 retrieved LNs (34.2%, 64.5%, and 62.7%, respectively; P = .047). Five-year OS did not significantly improve when the number of retrieved LNs was greater than 6. These results were confirmed in a receiver operating characteristic curve analysis performed among N0R0 patients, in whom 5 retrieved LNs was the most accurate cutoff to predict 5-year actual OS (area under the curve, 0.624; P = .004). Conclusions and Relevance An LNR exceeding 0.20 was the only independent prognostic factor for OS in N1 patients after liver resection for HC. However, the LNR was influenced by the total number of retrieved LNs, and removal of more than 5 LNs was the minimum number of LNs required for adequate staging.

Splitting the liver for two adults to increase the donor pool is still a debated issue, especially for combined organ transplantation. We described a case of liver-splitting procedure for two adults, which was successful even in the presence of combined organ transplantation. Three adult combined organ transplantations from one deceased donor were performed, with, use of split liver grafts in two patients: a combined heart-right split liver, a left kidney-left split liver, and a right kidney-pancreas transplantation. Despite a not perfect match between the graft type and recipient, the prevention of small-for-size syndrome by ligature of the splenic artery, and/or hemiportocaval shunt in the patient receiving the left split liver, and the maximal reduction of ischemia time were the main factors contributing to the success of the procedure. This is the first report of combined heart and split liver in two adults which may suggest new strategies for organ transplantations.

OBJECTIVE: To evaluate the results of surgical therapy for intrahepatic cholangiocarcinoma (ICC), the incidence and the management of recurrence, and to analyze the change in approach during 2 different periods. DESIGN: Retrospective study. PATIENTS AND METHODS: Patient and tumor characteristics, and overall and disease-free survival were analyzed in a series of 72 consecutive patients who underwent hepatic resection for ICC. Several factors likely to influence survival after resection were evaluated. Patients were divided into 2 groups according to the year of operation (before and after 1999). Management of recurrence and survival after recurrence were also analyzed. RESULTS: The 3- and 5-year overall survival rates were 62% and 48%, whereas the 3- and 5-year disease-free survival rates were 30% and 25%, respectively. The median survival time was 57.1 months. Patient and histologic characteristics before and after 1999 were similar. Survival was significantly better among patients operated after 1999, who were node-negative, did not receive blood transfusion, and underwent adjuvant chemotherapy. The overall recurrence rates before and after 1999 were comparable (66.6% and 50%, P = 0.49). The most frequent site of recurrence was the liver. A significantly large number of patients received treatment for recurrence after 1999 (81.5%) compared with the first period (8.3%). The overall 3-year survival rate after recurrence was 46%. After 1999, there was a significant improvement in 3-year survival after recurrence (56%) compared with patients operated before 1999 (0%, P = 0.004); the median survival time from the diagnosis of recurrence increased from 20 months to 66 months in the second group. CONCLUSIONS: Although recurrence rate represents a frequent problem in ICC, an aggressive approach to recurrence can significantly prolong survival.

BACKGROUND AND AIMS: The outcome of hepatic resection in cirrhotic patients has improved remarkably in recent years with improved surgical techniques and perioperative care; however, the role of portal hypertension is still uncertain. The aim of this study was to elucidate surgical outcomes of hepatectomy in patients with portal hypertension. METHODS: Data from 241 cirrhotic patients who underwent resection for hepatocellular carcinoma were retrospectively collected and analyzed: patients were divided into 2 groups according to the presence (n = 89) or absence (n = 152) of portal hypertension at the time of surgery. To overcome biases owing to the different distribution of covariates throughout the 2 groups, a one-to-one match was created using propensity score analysis: after match, intraoperative, and postoperative course and survival rates were analyzed. RESULTS: Patients with portal hypertension experienced worse preoperative liver function (mean model for end-stage liver disease [MELD] score, 9.5 +/- 7.8 vs. 8.4 +/- 1.3; P = 0.001) and survival rates (P = 0.008) in comparison to those without portal hypertension: after one-to-one matching, patients with (n = 78) and without portal hypertension (n = 78) had the same preoperative characteristics and showed the same intraoperative course, postoperative occurrence of liver failure, morbidity, length of in-hospital stay and survival rates (P = ns in all cases). The only predictors of postoperative liver failure were MELD score (P = 0.001) and extent of hepatectomy (P = 0.005). CONCLUSIONS: Faced with the same MELD score and extent of hepatectomy planning, presence of portal hypertension should not be considered as a contraindication for hepatic resection in cirrhotic patients.

The application of intestinal transplantation is limited by the high rate of infectious complications that can occur; the migration of enteric microorganisms to extraintestinal sites (bacterial translocation) has been suggested to be responsible for this event. We reviewed 95 intestinal biopsies performed on 28 transplanted patients to identify histologic features predictive of isolation of enteric microorganisms in extraintestinal sites within the first month after transplantation. At least 1 isolation of enteric microorganisms in the peritoneal cavity and/or in blood samples was obtained in 13 patients (46.4%); this event led to higher 1-year mortality (38.5% vs. 6.7%; P = .041). Of the 95 biopsies, 38 were followed by positive cultures (40.0%), showing higher degrees of mucosal vascular alterations (Ruiz grade) and ischemia/reperfusion injuries (Park/Chiu grade) compared with the negative cases (P < .05). We also observed an higher prevalence of positive cultures in relation to acute cellular rejection episodes (P = .091). Neither clinical or surgical factors nor immunosuppressive therapy were observed to be significantly related to positive cultures. Histologic alterations of the small bowel allograft are related to isolation of enteric microorganisms in extraintestinal sites. The degree of these histologic features can identify patients at high risk of potentially life-threatening infectious complications and death.

In this study we compared the content of muscle free [Mg2+] assessed by 31P MRS to that of serum total Mg assessed by routine colorimetric assays in 15 patients affected by Chronic Intestinal Failure (CIF) on long-term Home Parenteral Nutrition (HPN) or who had undergone isolated intestinal transplantation. We also investigated in the same cohort of patients the relationship of muscle free [Mg2+] and serum total Mg with parathyroid hormone (PTH) serum content. All patients showed a normal cytosolic free [Mg2+] in the calf muscle despite about half of them having a content of total serum [Mg] below or at the lower edge of the boundary limits. Muscle free Mg2+ and serum total Mg displayed an opposite correlation versus serum PTH, showing that the intracellular free form possesses a different functional metabolic meaning in the regulation of PTH secretion.

Background/Aims Orthotopic liver transplantation (OLT) is an important therapeutic option for HBV-related end-stage-liver disease, yet it is often hampered by a scarcity of organ availability. One option to increase organ availability is the use of virologically compromised organs from HBV-infected donors. Transplantation of anti-HBcore positive grafts has been associated with a low risk of HBV recurrence if adequately treated with nucleoside analogs, irrespective of concomitant HBV-specific immunoglobulin therapy. Experience using HBsAg positive grafts is, however, very limited. Methods Here, the analysis of the cellular and humoral HBV-specific immunity of a subject with past HBV infection (anti-HBs and anti-HBc positive) receiving an HBsAg positive liver graft is reported. Results Nine months post-OLT, the patient experienced a spontaneous anti-HBs re-seroconversion allowing the discontinuation of HBIG. The data show a concurrent increase in the cellular and humoral immunity at times of reduced viral antigenemia, demonstrating effective immune control of HBV post-OLT. Conclusions These data support the use of marginal organs in this setting, providing a potential strategy to further alleviate organ shortage.

Conventional criteria for liver transplantation for patients with hepatocellular carcinoma are single HCC

Advanced donor age is a risk factor for poor outcome in liver transplantation (LT). We reviewed 553 consecutive transplants according to donor age categories [group 1 (n = 173): or =80 years]. Clinical parameters were comparable between groups. Group 5 had the highest proportion of pretransplant liver biopsy (85%), with only 1 graft showing macrovesicular steatosis > 30%, and the lowest ischemia time. Five-year graft survival was significantly higher in group 1 (75%) versus groups 3 (60%) and 4 (62%; P = 0.01 and P = 0.001, respectively) and in group 5 (81%) versus groups 3 and 4 (P = 0.04 and P = 0.01, respectively). Donor age of 60-79 years, recipient hepatitis C virus-positive status, Model for End-Stage Liver Disease score > or = 25, and emergency LT were predictors of poor survival. In hepatitis C virus-positive patients, 5-year graft survival was 72% in group 1, 85% in group 2, 52% in group 3, 65% in group 4, and 71% in group 5 (group 1 versus group 3, P = 0.04; group 2 versus group 3, P = 0.03). In conclusion, older donor grafts managed with routine graft biopsy and short ischemia time may work effectively, regardless of the severity of the recipient's liver disease.

BACKGROUND.: The use of the Model for End-Stage Liver Disease (MELD) score to prioritize patients on liver waiting lists must take the bias of different laboratories into account. METHODS.: We evaluated the outcome of 418 patients listed during 1 year whose MELD score was computed by two laboratories (lab 1 and lab 2). The two labs had different normality ranges for bilirubin (maximal normal value [Vmax]: 1.1 for lab 1 and 1.2 for lab 2) and creatinine (Vmax: 1.2 for lab 1 and 1.4 for lab 2). The outcome during the waiting time was evaluated by considering the liver transplantations and the dropouts, which included deaths on the list, tumor progression, and patients who were too sick. RESULTS.: Although the clinical features of patients were similar between the two laboratories, 36 (13.1%) out of 275 were dropped from the list in lab 1, compared to 5 (3.5%) out of 143 in lab 2 (P

The best prioritization of patients with hepatocellular carcinoma (HCC) waiting for liver transplantation under the model for end-stage liver disease (MELD) allocation system is still being debated. We analyzed the impact of a MELD adjustment for HCC, which consisted of the addition of an extra score (based on the HCC stage and waiting time) to the native MELD score. The outcome was analyzed for 301 patients with chronic liver disease listed for liver transplantation between March 1, 2001 and February 28, 2003 [United Network for Organ Sharing (UNOS)-Child-Turcotte-Pugh (CTP) era, 163 patients, 28.8% with HCC] and between March 1, 2003 and February 28, 2004 (HCC-MELD era, 138 patients, 29.7% with HCC). In the HCC-MELD era, the cumulative dropout risk at 6 months was 17.6% for patients with HCC versus 22.3% for those patients without HCC (P = NS), similar to that in the UNOS-CTP era. The cumulative probability of transplantation at 6 months was 70.3% versus 39.0% (P = 0.005), being higher than that in the UNOS-CTP era for patients with HCC (P = 0.02). At the end of the HCC-MELD era, 12 patients with HCC (29.3%) versus 57 without HCC (58.8%) were still on the list (P = 0.001). Both native and adjusted MELD scores were higher (P < 0.05) and progressed more in patients with HCC who dropped out than in those who underwent transplantation or remained on the list (the initial-final native MELD scores were 17.3-23.1, 15.5-15.6, and 12.8-14.1, respectively). The patients without HCC remaining on the list showed stable MELD scores (initial-final: 15.1-15.4). In conclusion, the present data support the strategy of including the native MELD scores in the allocation system for HCC. This model allows the timely transplantation of patients with HCC without severely affecting the outcome of patients without HCC. Liver Transpl 13:857–866, 2007. © 2007 AASLD.

Background Pancreatic cancer represents a fatal malignancy leading to premature death and loss of life expectancy. The aim of the present study was to assess how many years of life are lost due to this cancer, in relationship with surgery and ageing. Methods Data from 716 consecutive patients discharged from a tertiary referral hospital (2002–2012) with a diagnosis of pancreatic cancer and with complete clinical and follow-up data were used to estimate the number of years of life-lost (YLL) through a semi-parametric extrapolation having an age-, sex- and year-of-onset- matched population derived from national life tables as reference. Results The mean entire lifespan estimated for the 716 patients was 1.4 years (95% C.I.:0.8–1.9) resulting in a number of YLL after diagnosis of 12 years (95% C.I.:11.5–12.6) per person. Surgical patients (147 cases; 20.5%) were younger and experienced higher post-diagnostic lifespan (3.5 years) than non-surgical older individuals (0.8 years; p < 0.001). These figures were reflected on the number of expected YLL (EYLL) that remained substantially unaffected by surgery (p = 0.821). Patients aged ≤68 years experienced the highest number of EYLL (20.8 years); whereas elderly patients had a loss of life that corresponded to only 6% of the entire life they had already lived. Conclusions In a typical pancreatic cancer cohort, surgery was not able to modify population-based statistics because of a different age at tumor onset which nullifies any benefit from a “lifespan from birth” perspective. Pancreatic cancer in younger individuals must be ranked within the very first causes of EYLL due to malignancy.

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.

Purpose We sought to evaluate liver function recovery after isolated intestinal transplantation in adults with irreversible intestinal failure. Patients and Methods Over a 5-year period, we transplanted 34 adult patients, 25 of whom received an isolated intestinal graft, 4 a multivisceral graft without a liver, and 5, a multivisceral graft with a liver. Among the group of patients transplanted with the isolated graft we selected 14 recipients with pretransplant liver dysfunction, namely, a serum bilirubin >2 mg/dL (normal value: 1.2) and/or transaminases >100 IU/mL (NV, 37/40). Other inclusion criteria were total parenteral nutrition, period > 3 months, no diagnosis of portal hypertension or cirrhosis. Two patients had biopsy-proven liver fibrosis. Results At discharge, all patients recovered liver function to normal values: mean bilirubin blood level was 0.9 ± 0.96 mg/dL (range: 0.3–1.6) and mean transaminases were 26 ± 9 and 31 ± 18 IU/mL (range: 10–44/27–65). After a mean follow-up of 2 years, only one patient has an elevated alanine aminotransferase level without clinical signs of liver disease. Type of pretransplant liver disease did not impact on survival rates. Conclusion In selected cases, an isolated intestinal or a multivisceral graft without a liver can represent a “liver salvage therapy” for an early failing liver in patients with irreversible intestinal failure. Pretransplant liver disease is not a negative prognostic factor.

The effect of ischemic preconditioning (IPC) in orthotopic liver transplantation (OLT) has not yet been clarified. We performed a pilot study to evaluate the effects of IPC in OLT by comparing the outcomes of recipients of grafts from deceased donors randomly assigned to receive (IPC+ group, n = 23) or not (IPC- group, n = 24) IPC (10-min ischemia + 15-min reperfusion). In 10 cases in the IPC+ group and in 12 in the IPC- group, the expression of inducible nitric oxide synthase (iNOS), neutrophil infiltration, and hepatocellular apoptosis were tested by immunohistochemistry in prereperfusion and postreperfusion biopsies. Median aspartate aminotransferase (AST) levels were lower in the IPC+ group vs. the IPC- group on postoperative days 1 and 2 (398 vs. 1,234 U/L, P = 0.002; and 283 vs. 685 U/L, P = 0.009). Alanine aminotransferases were lower in the IPC+ vs. the IPC- group on postoperative days 1, 2, and 3 (333 vs. 934 U/L, P = 0.016; 492 vs. 1,040 U/L, P = 0.008; and 386 vs. 735 U/L, P = 0.022). Bilirubin levels and prothrombin activity throughout the first 3 postoperative weeks, incidence of graft nonfunction and graft and patient survival rates were similar between groups. Prereperfusion and postreperfusion immunohistochemical parameters did not differ between groups. iNOS was higher postreperfusion vs. prereperfusion in the IPC- group (P = 0.008). Neutrophil infiltration was higher postreperfusion vs. prereperfusion in both groups (IPC+, P = 0.007; IPC-, P = 0.003). Prereperfusion and postreperfusion apoptosis was minimal in both groups. In conclusion, IPC reduced ischemia/reperfusion injury through a decrease of hepatocellular necrosis, but it showed no clinical benefits.

The complications concerning liver and intestinal transplant surgery have relevance for the field of intensive care because they share some characteristics with those following complex long-term surgery. Thus, in this article we shall try to describe complications that are specific to liver and multivisceral transplants. A review of the existing literature on this topic reveals a large number of studies dedicated to early as well as late surgical complications, and immunosuppressive treatment, while there are far fewer contributions describing complications exclusively concerning intensive care. We shall thus attempt to focus on certain aspects where, besides the literature data, we have personal experience. In particular we want to underline the implications of failure in the functional recovery of the graft; alterations in water, electrolyte, and glycemic balance; as well as neurological, respiratory, renal, nutritional, and infective complications.

BACKGROUND: To evaluate the role of liver resection for noncolorectal, nonneuroendocrine metastases, indications and results were retrospectively reviewed in 142 observed patients. METHODS: A curative liver resection was performed in 83 cases (58.5%), and the remaining 59 patients received palliative treatments. The primary tumor site was gastrointestinal in 18, breast in 21, genitourinary in 15, leiomyosarcoma in 10, and other in 19. The mean number of metastases was 1.4. The mean diameter of the nodules was 5.7 cm. Liver metastases were synchronous in 11 (13.3%) cases and metachronous in the remaining 72 (86.7%). RESULTS: There was no operative mortality. Postoperative morbidity was 20.5%. The median postoperative stay was 9.5 days. The 3- and 5-year actuarial survival rate was 49.5% and 34.3% in resected cases, respectively, whereas there were almost no survivors 3 years after diagnosis in unresected cases (P < .05). The 3- and 5-year disease-free survival was 41.4% and 23.8%, respectively. Among the 83 resected cases, the 3- and 5-year actuarial survival was 17.3% and 8.6% for metastases from gastrointestinal tumors, 53.9% and 24.6% from breast cancer, 63.7% and 36.4% from leiomyosarcoma, 50.4% and 37.8% from genitourinary neoplasms, and 55.6% and 42.4% from other sites, respectively. Fifteen patients (18.1%) survived longer than 5 years. CONCLUSIONS: Liver resection is an effective treatment for noncolorectal, nonneuroendocrine metastases; it allows satisfactory long-term survival with an acceptable operative risk in selected patients. Hepatic metastases from gastrointestinal carcinoma have the worst prognosis; those from genitourinary tumors show a better outcome. Patient selection is the key to achieving encouraging results.

The urea cycle is the final pathway for nitrogen metabolism. Urea cycle disorders (UCDs) include a variety of genetic defects, which lead to inefficient urea synthesis. Elevated blood ammonium level is usually dominant in the clinical pattern and the primary manifestations affect the central nervous system. Herein, we report the case of a 17-year-old girl who was diagnosed with UCD at the age of 3. Despite a controlled diet, she was hospitalized several times for acute attacks with recurrent life risk. She came to our attention for a hyperammonemic episode. We proposed an orthotopic liver transplant (OLT) as a treatment; the patient and her family were in complete agreement. On February 28, 2007, she successfully received a transplant. Following the surgery, she has remained well, and she is currently leading a normal life. Usually for UCDs diet plays the primary therapeutic role, while OLT is often considered as a last resort. Our case report and the recent literature data on the quality of life and prognosis of traditionally treated patients vs OLT patients, support OLT as a primary intervention to prevent life-threatening acute episodes and chronic mental impairment.

BACKGROUND & AIMS: Data on the safety of bevacizumab-based therapies for patients carrying a self-expandable metallic stent (SEMS) for occlusive colon cancer are lacking. We report 2 cases of colon perforation observed in our case series of patients with SEMS for occlusive colon cancer. METHODS: Patients with occlusive symptoms caused by colon cancer received a colonic stent under endoscopic and radiologic guidance. RESULTS: Over a 10-month period, 28 patients with occlusive colon cancer were treated with stent placement. The stent was placed as a bridge to surgery in 12 patients who were treated surgically within 4 to 78 days after the endoscopic procedures, without any stent-related complications. Seven patients did not receive any other antitumor treatment as a result of concomitant comorbidities. Nine patients with both primary tumor and metastatic lesions were treated with medical therapy. Over a median follow-up period of 131 days colonic perforation occurred in the 2 patients treated with a combination of capecitabine and oxaliplatin plus bevacizumab. CONCLUSIONS: Further studies are needed to clarify whether SEMS placement increases the risk of perforation caused by bevacizumab-based therapies.

The model for end-stage liver disease (MELD) is used to determine organ allocation priorities for orthotopic liver transplantation (OLT), although its value to predict posttransplantation mortality and morbility is controversial. The aim of this study was to analyze postoperative courses and (to evaluate the relationships between MELD score and postoperative) complications. We retrospectively examined the courses of 242 patients including 186 males and 56 females of overall mean age of 53 +/- 10 years who underwent primary liver transplantation. The classification of Dindo-characterized 5 grades of severity to evaluate postoperative events. The data showed that 171 patients (70.7%) experienced complications, while 71 (29.3%) had none. We observed that MELD score and complications were related (P < .05). Patients with complicated courses post-OLT displayed a 22.80 mean value of the MELD score, while those without complications showed a 17.64 mean value. The MELD score was also significantly associated with the time of intensive care unit stay and in hospital. Finally, we noted that MELD score and mortality were significantly correlated (P < .05). In conclusion, MELD score can be considered to be an objective system to predict the prevalence and severity of postoperative complications after liver transplantation.

INTRODUCTION: In our clinical context, there are two groups that practice blood purification treatments on acute or chronic liver failure (AoCLF) patients: one group used MARS (molecular adsorbent recirculating system) and the other Prometheus. MATERIALS AND METHODS: The MARS group used the lack of response to standard medical treatment after 72 hours of observation as the access criterion. The Prometheus group used the access criteria of the multicenter Helios protocol for patients in AoCLF, as well as those with primary nonfunction (PNF) and secondary liver insufficiency. Both groups performed treatment sessions of at least 6 hours, which were repeated at least every 24 to 36 hours. RESULTS: The 56 treated AoCLF patients underwent 278 treatment sessions; 41 out of 191 procedures with MARS and 16 out of 87 procedures with prometheus, which was also applied in two cases in PNF and four in secondary liver insufficiency. The results showed that both systems accomplished a good purification efficiency and that application to patients enabled reinstatement on the transplant list and grafts in 70% of the cases with either method. CONCLUSION: Treatment led to recovery in dysfunction among patients not destined for transplantation, achieved with a 48.5% 3-month survival in the MARS group and 33.5% in the Prometheus groups. The treatment results were inversely proportional to the MELD at the time of entry; The treatment appeared to be pointless. Among PNF and secondary liver insufficiency cases.

The analysis of intraoperative hemodynamic, metabolic, and coagulation disorders of the recipients in relation to the newly reperfused organ during intestinal transplantation is necessary for an optimal patient management during small bowel transplantation (SBT). The interaction may be minor or may lead to postreperfusion syndrome, producing intense hemodynamic instability, important metabolic changes, and coagulation disorders. This research is based upon experience with 27 patients who underwent SBT. We observed significant decreases in PAM and IRVS after reperfusion in accordance with minor changes of mean pulmonary artery pressure, central venous pressure, and pulmonary capillary wedge pressure. The fall in pH upon revascularization was associated with a concomitant rise in partial carbon dioxide pressure probably due to the increased metabolic activity of the new organ. We found a significant increase in K levels, a rise that may be due to the output of metabolic products by the donor intestine. Patients displayed an hypocoagulative pattern, a derangement that did not seem to depend on ischemia time. It is possible that the same factors supporting the initial TEG pattern endure throughout the surgical procedure. The important and significant maximum amplitude indicator variation between the initial value and that after reperfusion may relate to the release of hypocoagulative factors superimposed on background abnormalities. These interesting metabolic disorders presumably reflected graft function and may provide predictive indices for a good outcome.

Lead-time is the time by which diagnosis is anticipated by screening/surveillance with respect to the symptomatic detection of a disease. Any screening program, including surveillance for hepatocellular carcinoma (HCC), is subject to lead-time bias. Data regarding lead-time for HCC are lacking. Aims of the present study were to calculate lead-time and to assess its impact on the benefit obtainable from the surveillance of cirrhotic patients. Background & Aims: Lead-time is the time by which diagnosis is anticipated by screening/surveillance with respect to the symptomatic detection of a disease. Any screening program, including surveillance for hepatocellular carcinoma (HCC), is subject to lead-time bias. Data regarding lead-time for HCC are lacking. Aims of the present study were to calculate lead-time and to assess its impact on the benefit obtainable from the surveillance of cirrhotic patients. Methods: One-thousand three-hundred and eighty Child–Pugh class A/B patients from the ITA.LI.CA database, in whom HCC was detected during semiannual surveillance (n = 850), annual surveillance (n = 234) or when patients came when symptomatic (n = 296), were selected. Lead-time was estimated by means of appropriate formulas and Monte Carlo simulation, including 1000 patients for each arm. Results: The 5-year overall survival after HCC diagnosis was 32.7% in semiannually surveilled patients, 25.2% in annually surveilled patients, and 12.2% in symptomatic patients (p

Abdominal wall closure after intestinal transplantation in adult patients can be a difficult procedure. The main possibility offered by international experience is the use of myocutaneous flaps and abdominal wall transplantation. We report our experience in intestinal/multivisceral transplantation, including four difficult cases among 27 adult transplant recipients. Three patients underwent prosthetic mesh alone and one, a myocutaneous flap for abdominal closure after primary mesh positioning. We selected a mesh with a structure that allowed us to close the abdomen without creating adhesions and, at the same time, stimulating tissue repair. Two patients experienced local mesh infection, which has been kept under clinical control by antibiotics and daily medications till neoabdominal wall formation. The mesh was then removed. Another patient underwent mesh substitution for a suspicious fever. The last patient had mesh as a bridge for a subsequent myocutaneous flap from the thigh. All patients are in good health with well-functioning grafts and no need for parenteral nutrition. No enterocutaneous fistulae were detected.

Doppler ultrasonography (US) provides an accurate assessment of the hepatic vasculature in liver transplantation (LT). It can be performed perioperatively or at the bedside. The evaluation of the hepatic vessels includes color and spectral Doppler analysis. ColorDoppler provides information regarding the presence and direction of flow, as well as the location of turbulent flow in a post-stenotic segment. Spectral analysis describes the direction, velocity, and phasicity of flow.

BACKGROUND: Whether anatomic resection (AR) for hepatocellular carcinoma (HCC) can really confer a survival advantage over non-AR (NAR), especially for cirrhotic patients, remains unclear. METHODS: Prospectively collected data of 543 cirrhotic patients in Child-Pugh class A submitted to AR (n = 228) versus NAR (n = 315) for early HCC in an Eastern (n = 269) and a Western (n = 274) surgical unit, were reviewed. To control for confounding variable distributions, a 1-to-1 propensity score match was applied to compare AR and NAR outcomes (n = 298). RESULTS: The 5-year recurrence-free and overall survivals of the 543 patients were 32.3% and 60.0%, respectively, without differences between the 2 centers (P = .635 and .479, respectively). AR conferred better overall and recurrence-free survival than NAR (P = .009 and .041, respectively), but NAR patients suffered from significantly worse hepatic dysfunction. After 1-to-1 match, AR (n = 149) and NAR (n = 149) patients had similar covariate distributions. In this matched sample, AR still conferred better recurrence-free survival over NAR (P = .044) but the beneficial effect of AR was limited to the reduction of early recurrence (

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.