Impact of a Multidisciplinary Team on Alcohol Recidivism and Survival After Liver Transplant for Alcoholic Disease.

BACKGROUND: Alcohol use disorders have a prevalence of 10% among the population of the United States and Europe and are one of the most frequent causes of liver cirrhosis in the Western world. Currently, alcohol-related liver cirrhosis represents one of the most frequent indications to liver transplant (LT), both as independent cause or associated with hepatitis C virus or hepatitis B virus infections. Starting from 2014, a multidisciplinary team involving surgeons, gastroenterologists, clinical toxicologists, psychiatrists, and psychologists was developed within the Modena Liver Transplant Center. METHODS: We retrospectively reviewed our prospectively maintained institutional database of liver transplants in order to identify cirrhotic patients eligible for LT with a diagnosis of alcohol use disorder. RESULTS: A total of 756 liver transplants were performed at Policlinico University Hospital, University of Modena, and Reggio Emilia, MO, Italy, between November 2000 and November 2017; 102 patients who underwent LT were considered eligible for inclusion in the study. CONCLUSIONS: The multidisciplinary approach, together with blood, urinary, and hair tests, allows identification of early recurrences and improves survival. Further studies are necessary to understand how multidisciplinary teams can change the 6-month rule in patient selection.

Gastric Mucormycosis in a Liver and Kidney Transplant Recipient: Case Report and Concise Review of Literature.

Mucormycosis is an uncommonly encountered fungal infection in solid organ transplantation. The infection is severe and often results in a fatal outcome. The most common presentations are rhino-sino-orbital and pulmonary disease. We describe a rare case of gastric mucormycosis in a patient with a combined liver-kidney transplant affected by glycogen storage disease type Ia. A 42-year-old female patient presented with gastric pain and melena 26 days after transplantation. Evaluation with upper endoscopy showed two bleeding gastric ulcers. Histological examination of gastric specimens revealed fungal hyphae with evidence of Mucormycetes at subsequent molecular analysis. Immunosuppressive therapy was reduced and antifungal therapy consisting of liposomal amphotericin B and posaconazole was promptly introduced. Gastrointestinal side effects of posaconazole and acute T-cell rejection of renal graft complicated management of the case. A prolonged course of daily injections of amphotericin B together with a slight increase of immunosuppression favored successful treatment of mucormycosis as well as of graft rejection. At 2-year follow-up, the woman was found to have maintained normal renal and liver function. We conclude that judicious personalization of antimicrobial and antirejection therapy should be considered to resolve every life-threatening case of mucormycosis in solid organ transplantation.

Multimodal oncological approach in patients affected by recurrent hepatocellular carcinoma after liver transplantation.

OBJECTIVE: Hepatocellular Carcinoma (HCC) represents the fifth most common malignancy and the third cancer-related cause of death worldwide. Liver transplantation (LT) is an excellent treatment for patients with small HCC associated with cirrhosis. The purpose of this review is to investigate the possible strategies for the treatment of HCC recurrence after LT based on current clinical evidence. MATERIALS AND METHODS: A systematic literature search was performed independently by two of the authors using PubMed, EMBASE, Scopus and the Cochrane Library Central. The search was limited to studies in humans and to those reported in the English language. RESULTS: Thanks to the introduction of strict selection criteria, LT for HCC has achieved a survival rate of 85% at five years. However, the recurrence of HCC after transplantation remains a serious problem that affects about 20% of post-transplant cases. While most recurrences occur within the first 2 years, late recurrences have been described. The prognosis of recurrence is poor despite numerous proposals of the therapeutic option. Lower levels of immunosuppressive therapy and use of mammalian targets of rapamycin (mTORs) is a potential preventive strategy to reduce HCC recurrence post-Lt. Surgical resection and locoregional therapies (mainly TACE and RFA) play a very important role and are associated with improved survival. Conversely, multikinase inhibitors such as Sorafenib and their association with mTOR inhibitors play a role in cases of advanced HCC recurrence not suitable for the surgical or ablative approach. CONCLUSIONS: Treating HCC recurrence is a multidisciplinary workup involving hepatologists, surgeons, oncologists and radiologists in order to offer a patient-tailored therapy.

Vacuum-Assisted Closure Therapy in Patients Undergoing Liver Transplantation With Necessity to Maintain Open Abdomen.

BACKGROUND: Negative-pressure wound therapy (NPWT) has been recognized as a valid method of temporary abdominal closure. The role of open abdomen (OA) in the management of abdominal sepsis has been a controversial issue. Recent experimental and clinical studies have indicated that vacuum-assisted closure (VAC) is associated with superior outcomes in the treatment of OA conditions, but sufficient proof of efficacy and effectiveness is lacking. METHODS: We enrolled in this observational study all patients who had undergone liver transplantation (LT) for all causes between 2007 and 2014 in whom we needed to use VAC therapy, describing the pathology that led to the complication, length of hospitalization, graft survival, microbial identifications, and causes of death. RESULTS: We enrolled 11 patients-6 men (55%) and 5 women (45%), from 41.92 to 64.96 years old (mean, 57.62 ± 6.56 years) -who went to LT for different pathologies. The mean hospital stay was 56.72 ± 36.40 days (range, 8-133 days). Graft survival was 35.65 ± 31.61 months (range, 1.51-89.19 months). Six of 11 patients died (55%) of different causes; in particular, 4 patients died 1 to 3 months after the procedures that led to the condition of OA for septic shock and subsequent multi-organ failure. CONCLUSIONS: Complications related to the use of NPWT, such as painful management and bleeding, are rare and mild when the device is used properly. Although studies are needed to verify the real cost/benefit ratio in this application of VAC therapy, we consider it a useful means to treat the OA condition.

Incidental Intra-Hepatic Cholangiocarcinoma and Hepatocholangiocarcinoma in Liver Transplantation: A Single-Center Experience.

BACKGROUND: Cholangiocarcinoma (CCA) is an aggressive malignancy of the biliary tract that is a challenging issue for the medical community, with increasing incidence. Risk factors for CCA are similar to those known for hepatocellular carcinoma (HCC), such as cirrhosis, chronic hepatitis B and C, obesity, diabetes, and alcohol. We describe the outcome and the management of patients who underwent liver transplantation (LT) with an incidental diagnosis of intrahepatic (iCCA) or hepatocholangiocarcinoma (CHC). METHODS: From 2000 to May 2015, 655 LT were performed LT at the Liver Transplant Center in Modena, Italy. We retrospectively reviewed the pathological data of the explanted livers, finding 5 cases of iCCA or CHC. The pathological examination of the explanted livers showed 1 case of iCCA; 1 case of multifocal HCC associated with a nodule of iCCA; 2 cases of CHC associated with nodules of HCC; and 1 case of CHC associated with iCCA. Mean disease-free survival (DFS) was 15.49 months (1.55-42.04) and mean overall survival (OS) was 24.76 months (3.91-75.49). All patients died of recurrent tumor progression. RESULTS: iCCA incidental finding after LT affects patient outcomes, massively causing OS and DFS reduction. We stress the necessity of a more accurate selection of the candidates whenever an augmented risk of iCCA or CHC is present. CONCLUSIONS: Further investigations are required to better understand the role of LT in these patients and to define the best management for them once they have been transplanted and the histological examination reveals the presence of iCCA or CHC.

Multiple ways to manage portal thrombosis during liver transplantation: surgical techniques and outcomes.

BACKGROUND: Portal vein thrombosis (PVT) is a well-recognized complication of chronic liver disease with a prevalence ranging from 1% to 16%. MATERIALS AND METHODS: We performed a retrospective review of 447 consecutive patients who underwent liver transplantation (OLT) between October 2000 and December 2011 comparing 51 recipients with PVT (study group) with 399 without PVT (control group). The aim of this study was to determine the impact of pre-existent PVT on the surgical procedure, to identify specific preventable perioperative complications, and based on our studies and other works, to determine whether this group of patients are acceptable candidates for OLT. RESULTS: Among the 51 patients with PVT, 44 showed partial and 7 complete thrombosis. In 47 cases, we performed a thromboendovenectomy. There were six anastomoses at the confluence of the superior mesenteric vein (SMV) and one, with a venous graft interposition. In four complete thrombosis recipients we performed an extra-anatomic by pass between the main trunk of the SMV and the donor portal vein. Compared with the control group, regarding preoperative characteristics, PVT patients were older at the time of transplantation (P = .001) and had a higher use of TIPS (P = .02). The operative characteristics showed a longer warm ischemia time in the PVT group (46.9 ± 22.5 vs 39.3 ± 15 min; P = .004). There were significant differences in postoperative evaluations, nor in the complication rates. Overall survivals at 10 years were similar: 61.7% versus 65.3%; (P = .9). CONCLUSION: Although PVT was associated with greater operative complexity, it had no influence on postoperative complications or overall survival.

University of Modena experience in HIV-positive patients undergoing liver transplantation.

INTRODUCTION: Highly effective antiretroviral therapy in the last decade has increased the survival rates of HIV-positive patients, yielding a greater number of HIV patients suffering from liver-related disease. Liver transplantation (LT) is the only curative treatment for end-stage liver disease (ESLD) associated or not with hepatocellular carcinoma (HCC). PATIENTS AND METHODS: From June 2003 to September 2010, 23 patients underwent cadaveric donor LT for ESLD at our institution. Inclusion criteria followed the Italian Protocol for LT in HIV-positive patients. Immunosuppressive regimens were based on cyclosporine or tacrolimus, eventually switched to Rapamycin. RESULTS: The median CD4 T-cell count was 275/mmc (range=119-924). All patients were affected by ESLD, which was associated with HCC in 14 cases. Ten patients were within the Milan criteria and four patients exceeded them but were within the San Francisco criteria. Conversion from calcineurin inhibitors (CNI) to rapamycin occurred in ten cases. Hepatitis C virus (HCV) recurrence occurred in 13/21 HCV-positive patients. Acute cellular rejection occurred in eight patients with one developing chronic cellular rejection. Overall patient and graft survivals at 80 months were 50% and 45% respectively. DISCUSSION: LT in HIV-positive patients is a feasible procedure, even if in our experience was burdened by a greater incidence of complications including HCV recurrence and infection compared with HIV-negative patients.

Combined liver-kidney transplantation in patients infected with human immunodeficiency virus.

Although human immunodeficiency virus (HIV) infection has been a major global health problem for almost 3 decades, with the introduction of highly active antiretroviral therapy in 1996 and effective prophylaxis and management of opportunistic infections, mortality from acquired immunodeficiency syndrome has decreased markedly. In developed countries, this condition is now being treated as a chronic condition. As a result, rates of morbidity and mortality from other medical conditions leading to end-stage liver, kidney, and heart disease are steadily increasing in individuals with HIV. Because the definitive treatment for end-stage organ failure is transplantation, the demand for it has increased among HIV-infected patients. For these reasons, many transplant centers have eliminated HIV infection as a contraindication to transplantation, as a result of better patient management and demand.

Novel genetic mutation in apolipoprotein E2 homozygosis and its implication in organ donation: a case report.

Disorders in lipoprotein metabolism do not contraindicate liver procurement and transplantation (LT). In this circumstance, LT provides an intriguing opportunity to assess the in vivo contribution of the liver to the synthesis and degradation of genetically polymorphic plasma proteins. Apolipoprotein (APO) E exists with several common phenotypic differences due to gene polymorphism. Some authors have shown that the APOE phenotype of the recipient was virtually completely converted to that of the donor, providing evidence that >90% of plasma APOE arises from the liver. Homozygosis for APOE2 (E2-E2) is related to an increased incidence of type III hyperlipoproteinemia (HLP). Recently, some authors have identified 4 new APOE mutations that are strongly linked to a unique entity of renal lipidosis called lipoprotein glomerulopathy (LPG). At present, 65 cases of LPG have been reported worldwide, although most patients have been discovered in Japan and other East Asian countries. We have herein reported a case of LT in a patient with advanced hepatocarcinoma who received a liver from a caucasian donor affected by type III HLP due to homozygous E2-E2. The LPG was due to a novel genetic mutation in APOE. After the LT, the recipient, developed de novo severe lipid abnormalities despite good graft function. To our knowledge this is the first report of an LT using a graft from a non Asian donor with homozygous E2-E2 with the presence of a novel APOE mutation.

Liver transplantation due to iatrogenic injuries: two case reports.

The transjugular intrahepatic portosystemic shunt (TIPS) is an acceptable procedure that has proven benefits in the treatment of patients who have complications from portal hypertension due to liver cirrhosis. In the literature few reports have described complications after TIPS placement. Initial surgery and local hemostasis have been needed to manage abdominal bleeding: if this treatment is insufficient, it may be necessary to perform a liver transplantation. This report describes the role of liver transplantation to manage dangerous complications in 2 patients after TIPS placement, when surgical procedures and hemostasis were unable to stop the bleeding.

Liver transplantation in patients aged 65 and over: a case-control study.

INTRODUCTION: The average age of patients undergoing liver transplantation (LT) is consistently increasing. The aim of this case-control study is to evaluate survival and outcome of patients ≥65 yr compared to younger patients undergoing LT. MATERIALS AND METHODS: From 10/00 to 4/08 we performed 330 primary LT, 31 (9.4%) of these were in patients aged 65-70. Following a case-control approach, we compared these patients with 31 patients aged between 41 and 64 yr and matched according to sex, LT indication, viral status, cadaveric/living donor, LT timing, and Model for End-Stage Liver Disease (MELD) score. RESULTS: There were no statistically significant differences in demographic and surgical donor characteristics. The mean MELD score was under 18 in both groups. Post-LT complications occurred with a similar incidence in the two groups. one-, three-, and five-yr survival was 83.9%, 80.6%, and 80.6%, respectively, for the elderly group, and 80.6%, 73.8%, and 73.8%, respectively, for the young group (p = 0.61). DISCUSSION: Patients aged between 65 and 70 with low MELD score who undergo LT have the same short- and middle-term survival expectancy, morbidity, and outcome quality as younger patients with the same indication and same pre-LT pathology severity, whatever they might be. Thus, chronological age alone should not deter LT workup in patients >65 and <70.

[Is there an age limit for radical surgery in case of tumors infiltrating the duodenum?]. / Per le neoplasie infiltranti il duodeno esiste un limite di età per una chirurgia radicale?

AIM: Radical resection is the only potential cure for pancreatic malignancies and a useful treatment for other benign diseases, such as pancreatitis. Over the last two decades, medical and surgical improvements have drastically changed the postoperative outcome of elderly patients undergoing pancreatic resection, and appropriate treatment for elderly potential candidates for pancreatic resection has become an important issue. METHODS: A hundred and five consecutive patients undergoing radical pancreatic resection between 2003 and 2007 at the Surgery Unit of the University of Modena, Italy, were considered and divided into two groups according to their age, i.e., over 75-year olds (group 1, 25 patients) and under 75-year-olds (group 2, 80 patients). The two groups were compared as regards to demographic features, American Society of Anesthesiologists scores, comorbidities, previous major surgery, surgical procedure, postoperative mortality, and morbidity. RESULTS: There were no significant differences between the two groups concerning postoperative mortality, and the duration of hospital stay and days in the postoperative Intensive Care Unit were also similar. Complications such as pancreatic fistulas, wound infections, and pneumonia were more frequent in the older group, but the differences were not statistically significant. CONCLUSION: In the light of these findings and as reported for other series, old age is probably not directly related with any increase in the rate of postoperative complications, but comorbidities (which are naturally related to the patients' previous life) may have a key role in the postoperative course.

Liver transplantation utilizing grafts from donors with genitourinary cancer detected prior to liver implantation.

Expansion of the donor pool has led to reconsideration of selection criteria to obtain the largest number of grafts without compromising recipient outcomes. This reconsideration concerns the utilization of donors with malignancies. Herein we have analyzed the outcomes, survivals, and risks of cancer transmission among patients who received a liver transplant from a donor with a genitourinary malignancy. Six of 363 patients (1.5%) who underwent transplantation at our center received an organ from a donor with a genitourinary cancer which was detected prior to the surgical harvest. Donors affected by low-grade renal cell carcinoma (Fuhrman grade 1 or 2) or low-grade intraprostatic prostate carcinoma (Gleason score

Immunosuppressive switch to sirolimus in renal dysfunction after liver transplantation.

OBJECTIVE: Nephrotoxicity is a serious adverse effect after liver transplantation often related to calcineurin inhibitors (CNI) with a incidence of 18.1% at 5 years. Sirolimus (SRL) is a new immunosuppressive drug that was introduced into solid organ transplant management in 1999. Herein we have performed a retrospective review of patients who developed renal insufficiency owing to CNI therapy after orthotopic liver transplantation (OLT). MATERIALS AND METHODS: Thirty-one patients were switched to SRL monotherapy because of nephrotoxicity as evidenced by serum creatinine levels (SCr) > 1.8 mg/dL and estimated glomerular filtration rates (eGFR) < 45 mL/min/1.73 m(2). The dosage was adjusted to achieve trough levels between 8 and 10 ng/mL. RESULTS: The patients were followed for a mean of 52 months (range 2-88 months) after OLT. Mean follow-up after the switch was 27.5 months (range, 2-71.2 months). Immunosuppression was switched after a mean of 35.2 months (range, 0.2-43.4 months). Renal function was significantly improved, as shown by the improved SCr, urea, and eGFR after the switch. CONCLUSIONS: CNIs may be associated with significant nephrotoxicity and chronic kidney damage. Patients who develop renal dysfunction after OLT may be successfully treated by an early switch from CNIs to SRL, stopping the progression toward chronic renal damage and preserving allograft survival.

Model for End-Stage Liver Disease (MELD) system to allocate and to share livers: experience of two Italian centers.

BACKGROUND: The use of the Model for End-stage Liver Disease (MELD) score to prioritize patients on liver waiting lists and to share organs among centers was effective according to US data, but few reports are available in Europe. MATERIALS AND METHODS: We evaluated the outcome of 887 patients listed between April 2004 and July 2006 in a common list by two transplant centers (University of Bologna [BO] and University of Modena [MO] ordered according to the MELD system. Patients with hepatocellular carcinoma had a score calculated according to their real MELD, tumor stage, and waiting time. RESULTS: Five hundred eighty-six (67%) patients were listed from BO and 291 (33%) from MO. The clinical features of recipients (sex, age, blood group, and real MELD) were comparable between centers. The number of liver transplantations performed was 307, and 273 (89%) recipients had a calculated MELD >or=20. Liver transplantations were equally distributed according to the number of patients listed: 215 out of 586 (36.7%) for BO and 92 out of 291 (31.6%) for MO. The median real MELD of patients transplanted was 20, and 246 out of 307 (80.1%) grafts transplanted were functioning. The dropouts from the list were 124 (14%), and 87 (70%) of these patients had a calculated MELD >or=20. CONCLUSION: The MELD system was effective to share livers among the two Italian centers. According to this policy, livers were allocated to the recipients with the highest probability of dropout and who had a satisfactory survival after liver transplantation.

Temporary porto-caval shunt utility during orthotopic liver transplantation.

INTRODUCTION: In liver transplantation (OLT) a porto-caval shunt is a well-defined technique practiced by many surgeons in several centers. METHODS: We considered 186 cadaveric OLT patients who underwent a cavo-cavostomy-type reconstruction; they were divided into two groups: those in whom we performed a porto-caval shunt (group A) and those in whose we did not (group B). We evaluated several variables: warm and total ischemia time, intraoperative blood and fresh frozen plasma transfusions, crystalloid and colloid requirements, blood loss, operative duration, hemodynamic intraoperative changes and diuresis, length of hospital stay, and creatinine values at days 1 and 2, and at discharge day. RESULTS: Total and warm ischemic time differed significantly between the two groups. Infusion of blood, fresh frozen plasma, colloid, and crystalloid did not significantly differ. Blood loss was lower, and intraoperative diuresis was not significantly increased in group A subjects. Postoperative hospitalizations were 16.5 and 17.8 days and operative times, 504 and 611 minutes in the two groups. Both cardiac index and ejection fraction values during the anhepatic phase were significantly greater among group A than group B patients. PAD at the two phases was greater in group B. The PAS was significantly different only at reperfusion time. Creatinine values were significantly different at discharge. Better survival was shown for group A patients over group B subjects. CONCLUSION: The results presented herein confirmed that a porto-caval shunt during OLT was a safe, useful expedient contributing to an improved hemodynamic status and a better time distribution in the various phases of liver transplantation.