Everolimus vs Mycophenolate Mofetil in Combination With Tacrolimus: A Propensity Score-matched Analysis in Liver Transplantation.

BACKGROUND: No trial has investigated the long-term outcome of everolimus (EVR)-incorporating immunosuppression vs tacrolimus (TAC) and mycophenolate mofetil (MMF) after liver transplantation. MATERIALS AND METHODS: With a propensity score methodology, 178 recipients on TAC and MMF were compared to 178 patients on TAC and EVR. RESULTS: At a median (interquartile range) follow-up of 45 (46.3) months, the probability of treated biopsy-proven acute rejection, graft loss, and death was 36.6% for MMF and 28.1% for EVR (P = .0891). Treated biopsy-proven acute rejection was numerically lower for EVR (3.3% vs 7.3%, P = .09), while adverse events (70.2% vs 58.9%, P = .02) and drug discontinuations (21.3% vs 11.8%, P = .01) were significantly higher with regard to hypercholesterolemia (P = .001), thrombocytopenia (P = .0062), and edema (P = .0107). Patients on MMF showed more hypertension (P = .0315), tremor (P = .0006), cytomegalovirus infection (P = .0165), and malignancies (P = .0175). EVR was associated with lesser deterioration in mean (SD) renal function at the latest follow-up (-2.2 (1.8) vs -5.1 (3.2) mL/min/1.73 m2, t = 3.6, P = .005). CONCLUSIONS: The efficacy of the combination of TAC and EVR is comparable to that of TAC and MMF. Drug discontinuations and adverse events were higher for patients on EVR, but these latter showed less hypertension, cytomegalovirus infection, and renal dysfunction. The observed reduction in posttransplant malignancies for EVR requires longer follow-up to be confirmed.

Salvage of an Octogenarian Liver Graft Using Normothermic Perfusion: A Case Report.

Liver transplantation with very old donors is safe, but is associated with an increased incidence of ischemic-type biliary lesions and delayed graft function. Normothermic machine perfusion (NMP) is a novel technique for preservation of liver grafts and has the potential to reduce ischemia-reperfusion injury. A case is reported here of a liver transplantation (LT) with a graft from an 83-year-old brain-dead donor. Procurement was with dual perfusion and en bloc, modified fast technique. Donor kidneys were not transplanted due to severe atherosclerosis and poor perfusion. The liver was shipped to the transplantation center and underwent NMP with a blood-based perfusate. During machine perfusion lactates decreased, vascular flow was stable, and bile production restored, and the graft was considered suitable for transplantation. The postoperative course was uneventful and 4 months after surgery the patient is in good clinical condition with normal liver function. To date, few LTs have been performed with NMP in humans, but its preliminary results are promising. NMP allows functional evaluation of the graft and possibly reduction of post-transplantation complications when extended-criteria donor grafts are used.

Use of octogenarian donors for liver transplantation: a survival analysis.

Use of very old donors in liver transplantation (LT) is controversial because advanced donor age is associated with a higher risk for graft dysfunction and worse long-term results, especially for hepatitis C virus (HCV)-positive recipients. This was a retrospective, single-center review of primary, ABO-compatible LT performed between 2001 and 2010. Recipients were stratified in four groups based on donor age (<60 years; 60-69 years; 70-79 years and ≥80 years) and their outcomes were compared. A total of 842 patients were included: 348 (41.3%) with donors <60 years; 176 (20.9%) with donors 60-69 years; 233 (27.7%) with donors 70-79 years and 85 (10.1%) with donors ≥80 years. There was no difference across groups in terms of early (≤30 days) graft loss, and graft survival at 1 and 5 years was 90.5% and 78.6% for grafts <60 years; 88.6% and 81.3% for grafts 60-69 years; 87.6% and 75.1% for grafts 70-79 years and 84.7% and 77.1% for grafts ≥80 years (p = 0.065). In the group ≥80 years, the 5-year graft survival was lower for HCV-positive versus HCV-negative recipients (62.4% vs. 85.6%, p = 0.034). Based on our experience, grafts from donors ≥80 years may provide favorable results but require appropriate selection and allocation policies.

Efficacy and safety of combination therapy with everolimus and sorafenib for recurrence of hepatocellular carcinoma after liver transplantation.

BACKGROUND: Recurrence of hepatocellular carcinoma (HCC) after liver transplantation (LT) is still associated with a dismal outcome. Combination therapy with everolimus (EVL) and vascular endothelial growth factor inhibitor sorafenib (SORA) is based on the role of both b-Raf and mammalian target of rapamycin/protein kinase B pathways in the pathogenesis of HCC and is being investigated in clinical practice. METHODS: This was a single-center retrospective analysis on LT recipients with unresectable HCC recurrence and undergoing combination therapy with EVL and SORA. Patients were included if they were switched to EVL+SORA at any time after surgery. Primary endpoint was overall survival (OS) after both LT and recurrence, and response to treatment based on the modified Response Evaluation Criteria in Solid Tumors (mRECIST) in the intention-to-treat (ITT) population. Secondary analysis was safety of combination therapy with EVL and SORA in the population of patients who received ≥1 dose of the study drug. RESULTS: Seven patients (100% male; median age 53 years [interquartile range (IQR) 9 years]) were considered for analysis. HCC recurrence was diagnosed at a median (IQR) interval since LT of 9 (126) months, and patients were administered EVL+SORA at a median interval since LT of 11 (126) months. Baseline immunosuppression was with tacrolimus (TAC) in 2 patients (28.6%), cyclosporine (CsA) in 2 (28.6%), and EVL monotherapy in 3 (42.8%). At a median (IQR) follow-up of 6.5 (14) months, 5 patients (71.4%) were alive, 4 of them (57.1%) with tumor progression according to the mRECIST criteria. Median (IQR) time to progression was 3.5 (12) months. Two patients died at a median (IQR) follow-up of 5 (1) months owing to tumor progression in 1 patient (14.3%) and sepsis in the other (14.3%). EVL monotherapy was achieved in 6 patients (85.7%), whereas 1patient (14.3%) could not withdraw from calcineurin inhibitor owing to acute rejection. Treatment complications were: hand-foot syndrome in 5 patients (71.4%), hypertension in 1 (14.3%), alopecia in 1 (14.3%), hypothyroidism in 1 (14.3%), diarrhea in 2 (28.6%), pruritus in 1 (14.3%), abdominal pain in 1 (14.3%), rash in 1 (14.3%), asthenia in 3 (42.8%), anorexia in 3 (42.8%), and hoarseness in 2 (28.6%). Adverse events led to temporary SORA discontinuation in 2 patients (28.6%) and to SORA dose reduction in 3 (42.8%). CONCLUSIONS: Treatment of HCC recurrence after LT with a combination regimen of EVL+ SORA is challenging because of SORA-related complications. Longer follow-up periods and larger series are needed to better capture the impact of such combination treatment on tumor progression and patient survival.

Organ sharing in the management of acute liver failure.

BACKGROUND: Liver transplantation (OLT) for acute liver failure (ALF) is associated with high morbidity and mortality rates in the early posttransplant course. An efficient organ-sharing organization may grant favorable results. METHODS: This is a retrospective analysis of prospectively collected data on patients wait listed for ALF at a single center. Patients were listed for OLT when matching King's College Criteria. Based on patients' clinical status, ABO-incompatible grafts were used. RESULTS: From January 2001 to December 2010, 37 patients were wait listed for ALF. Two patients were de-listed (5.4%) for improvement of their clinical conditions; two patients (5.4%) died on the list and 33 (89.2%) underwent OLT. Among these latter, 21 (63.6%) were Italian and 12 (36.4%) were foreign citizens, with four referred from their home country on the basis of international agreements on ALF management. Donors were procured in our region in 10 cases (30.3%), nationally in 22 (66.6%), and outside Italy in 1 (3.1%). Mean time from wait listing to OLT was 1 day (range 0-6), and seven patients received an ABO-incompatible graft. Graft and patient survivals at 1 month, 1 year, and 3 years were 78.8%, 72.7%, 66.5%, and 81.8%, 75.8%, and 72.7%, respectively. Five patients underwent retransplantation: two on postoperative day (POD) 2 for primary nonfunction of the liver graft, two on POD 8 and 95 for hepatic artery thrombosis, and one at 18 months for nonanastomotic biliary stenosis. CONCLUSIONS: Prompt referral to a OLT center and efficient organ-sharing system play a fundamental role in optimizing the outcome of the patient with ALF. Development of international organ exchange programs might further improve the results for this category of patients. In very selected cases, ABO-incompatible grafts may be a valuable resource.

Analysis of patients' needs after liver transplantation in Tuscany: a prevalence study.

BACKGROUND: The reorganization of the healthcare system in Tuscany aims at characterizing the hospitals as a place for the treatment of acute patients. This event, together with the improvement of long-term survival after orthotopic liver transplantation (OLT), calls for a management network able to ensure effective continuity of care for patient needs in the posttransplantation period. MATERIALS AND METHODS: An observational study of prevalence has been carried out with the primary objective to evaluate patients' needs and criticalities both in routine daily life and in urgency in the posttransplantation period and the capacity of the regional health system to support them. A survey, using a semi-structured questionnaire consisting of 27 questions, was administered to all patients resident in Tuscany who underwent transplantation from 2000 to 2010. The survey tool assessed the following: socio-demographic data, personal, family and social difficulties, problems emerged in the clinical routine and urgency, resolution modality, relationships with the general practitioner and the referral specialist, and services the patients would appreciate receiving in their province of residence. RESULTS: In the study, 346 patients matched the inclusion criteria of the study, 324 gave telephone consent to participate in the survey, and 225 responded (69.4%). The most frequent difficulties were as follows: depression (39.5%), difficulty in returning to work (29.3%), low income (22.6%), lack of self-sufficiency (22.6%), addictions (19.1%) (cigarette smoking 16.4%), 12.4% eating disorders, and 18.9% other difficulties (social isolation, absence of a family network, and so on). The main reasons for dissatisfaction were as follows: difficulty to obtain the required laboratory tests and lack of a reference structure at the local health facility. Few patients have a referral specialists in their area and most of them primarily refer to the Transplant Center even late after the procedure. DISCUSSION: Early diagnosis of specific conditions (depression, addiction, and eating disorders) should be implemented in the follow-up period and services such as counselling, dietary support, rehabilitation, and social services should be provided locally. An integrated management system between the transplantation center and the local facilities (hospitals, general practitioners, primary care, and laboratories) should be implemented and referral specialized centers should be identified locally.

Alcohol abstinence and orthotopic liver transplantation in alcoholic liver cirrhosis.

Patients diagnosed with acute alcoholic hepatitis (AAH) are routinely managed medically and not considered suitable for orthotopic liver transplantation (OLT). The eligibility for OLT in these patients has been questioned due to the social stigma associated with alcohol abuse, based on the fact that AAH is "self-induced" with an unacceptably high recidivism rate. Many centers in Europe and the United States require abstinence periods between 6 and 12 months before OLT listing. AAH outcomes in the literature are poor, in particular due to patient noncompliance during the immediate 3 months preceeding OLT. Between January 1997 and December 2007, 246 patients were evaluated in our center for alcoholic liver disease: 133 (54%) were listed for OLT (I-OLT), including 110 (83%) who underwent transplantation and 8 (6%) still listed as well as 15 (11%) removed from consideration. One hundred thirteen (46%) patients had no indication for OLT (NO I-OLT), including 18 (16%) who died, 81 (71%) still monitored, and 14 (12%) lost to follow-up. Patient survival rates post-OLT were 79%, 74%, 68%, and 64% at 1, 3, 5, and 10 years, respectively. Explant (native liver) pathologic examination revealed AAH in 8 (7.2%) patients who underwent OLT. In this group, patient survival and the post-OLT recidivism rate were statistically identical to the overall group of transplant recipients.

Renal transplant compartment syndrome: a case report.

An unusual case of early double kidney transplant dysfunction due to abdominal compartment syndrome is herein reported. A 62-year-old woman on peritoneal dialysis underwent dual kidney transplantation. The grafts were positioned extraperitoneally in both iliac possae using standard techniques. Surgical procedures and immediate postoperative period were uneventful. The urine output was immediate and the creatinine decreased, but in a few days she developed severe ascites with reduced urine output, increased creatinine, and progressive changes on Doppler ultrasound. The patient underwent paracentesis: the kidney function recovered as well as the Doppler ultrasound. Kidney biopsy was negative for rejection or renal pathology. Graft dysfunction was related to the presence of ascites. A catheter inserted in the abdomen measured intra-abdominal pressure (IAP) of 14 mm Hg. IAP correlated with renal function showing that IAP probably explained renal flow modifications.

Dopamine "renal dose" versus fenoldopam mesylate to prevent ischemia-reperfusion injury in renal transplantation.

Low dose of dopamine is commonly used after kidney transplantation as a reno-protective agent, although its benefits are controversial. Dopamine may increase renal blood flow, decrease resistive index (RI), and induce urine output in normal kidneys. Many authors hypothesized that the vasculature of a denervated renal transplant may not respond to dopamine in the same fashion as healthy native kidneys, which led us to find other drugs to attenuate the ischemia-reperfusion (I/R) injury. Fenoldopam is a selective dopamine1 (DA1) receptor agonist, most of the activity of which resides in the R-enantiomer, which also shows weaker alpha 2-adrenoceptor antagonist activities. Fenoldopam produces a vasidilatory effect in vascular beds that are rich in vascular DA1 receptors, producing increased renal blood flow at doses that do not affect blood pressure. In addition to its renal vasodilator activity, fenoldopam is natriuretic, possibly resulting from a direct effect of DA1 receptors on the proximal convoluted tubule. In animals with spontaneous or drug-induced renal failure, fenoldopam improves renal function. The aim of this study was to investigate the possible effects of fenoldopan mesylate in recent kidney transplants. Creatinine, blood urea nitrogen, urine output, and renal vascular resistive index (IR) were measured using Doppler ultrasound. Two groups of patients with no statistical differences in demographic data were treated with dopamine or fenoldopan, showing no significant difference but a trend favoring the fenoldopan group.

[Cystic lymphangioma of the adult: our experience and review of literature]. / Linfangioma cistico dell'adulto: nostra esperienza e revisione della letteratura.

Cystic lymphangioma is an uncommon benign pathology, usually reported in children, rarely in adult. Its embryopathogenesis is still controversial: it seems to arise from the lymphatic vessels, mainly in the cervico-cranial district. It is macroscopically characterised by multiple cystic non-communicating concamerations. Definitive diagnosis used to be intraoperative and was usually an unexpected finding. Nowadays, with modern imaging technologies, CT and MRI, diagnosis can be assumed before intervention even though certain diagnosis can still be reached only with histological examination. Imaging techniques can help for a precise mapping of the lesion and definition of its limits with the other structures, improving therapeutic success. Various therapeutical options are reported in literature, but complete surgical excision is still considered the best approach and the most successful. The Authors report their experience and review the literature on cystic lymphangioma in adult.

Simultaneous liver-kidney transplantation for glycogen storage disease type IA (von Gierke's disease).

INTRODUCTION: Glycogen storage disease type Ia (GSDIa) is due to the deficiency of glucose-6-phosphatase activity in the liver, kidney, and intestine. Although significant progress has been achieved in the management of patients with GSDIa, complications still emerge. The potential for development of liver adenomatosis and kidney failure makes these patients candidates for simultaneous liver-kidney transplantation (SLKT). Herein, we describe such a transplantation in a patient affected by this rare storage disease. METHODS: A 25-year-old female patient with GSDIa developed hepatic adenoma and kidney failure despite dietary therapy. The patient underwent an SLKT from a cadaveric donor. RESULTS: The operative time was 8 hours without hemotransfusion. Only a transitory lactic acidosis was observed. Laboratory results normalized on postoperative day 7. The patient was discharged on postoperative day 9. After 4 months, the patient is in good condition with well-functioning kidney and liver allografts. CONCLUSION: Patients with end-stage renal disease secondary to GSDIa should be considered for SLKT, especially when the disease is in an early stage.

Preliminary report on impact of pretransplant dialysis on early graft function: peritoneal versus hemodialysis.

Delayed graft function and acute renal failure after kidney transplant negatively influence graft outcome. It has been reported that pretransplantation peritoneal dialysis (PD) instead of hemodialysis (HD) correlated with better short-term graft outcome in adult kidney recipients. In this study the impact of PD versus HD was evaluated among pediatric kidney recipients. This study suggested that different forms of dialysis pretransplantation did not affect early graft function among pediatric kidney recipients.

Severe rhabdomyolysis and acute renal failure in a kidney transplant patient treated with tacrolimus and chimaeric CD25 monoclonal antibody.

Recently observations of rhabdomyolysis in patients treated with tacrolimus have been reported. The authors present a kidney transplant patient who had an epileptic seizures, severe rhabdomyolysis, and acute renal failure. The patient was initially immunosuppressed with tacrolimus and chimeric CD25 monoclonal antibody. After intensive therapy with plasmapheresis, CVVH, and dialysis, the patient completely recovered at 11/2 year his serum creatinine is 1.2 mg/dL.

[Total splenectomy for a recurrent giant splenic cyst]. / Splenectomia totale per voluminosa cisti splenica recidiva.

Primary splenic cysts are a rare finding. Some are large and require surgical removal. The Authors report a case of a recurrent huge splenic cyst in a 41-year-old female patient. A marsupialization was performed at another hospital 6 years before. Ultrasonography and computed tomography imaging revealed a cystic lesion in the spleen measuring approximately 20 cm in diameter. A total open splenectomy was performed. Postoperative course was uneventful. The histologic diagnosis was an epithelial cyst of the spleen with no atypical cells in the cyst wall, as previously found at the first operation. The epidermoid cysts have an epidermal lining, and prevention of recurrence is dependent on complete resection of the cyst wall preserving, whenever possible, the splenic tissue. Recurrence can be avoided with partial splenectomy in polar localization of the cyst, or complete removal of the cyst by "peeling" it off the splenic parenchyma. Marsupialization of the cyst, either via a laparoscopic or an open approach, is often ineffective.

[Deep venous thrombosis after leg amputation. Review of the argument]. / La trombosi venosa profonda dopo amputazione degli arti inferiori. Review sull'argomento.

Patients undergoing lower extremity amputation are perceived to be at high risk for deep vein thrombosis (DVT). DVT can cause micro or macro pulmonary embolism and often the post-thrombophlebitic syndrome. The chronic condition can affect patient quality of life and his residual working capacity. Usually the echo-Doppler or the color-Doppler is used as a prevention and diagnostic method, identifying patients at high risk. Following the Authors examine and report the Literature opinion about the topics.