choledocotomy was performed in 7 patients (25%). Primary or T-Tube choledocorraphy was performed ... more choledocotomy was performed in 7 patients (25%). Primary or T-Tube choledocorraphy was performed in 5 (18%) and 2 patients (0,07%) respectively. The procedure was successful in 27 patients (96%). Due to hemodynamic instability, the procedure was finished prematurely in 1 patient leaving one stone and placing a T-Tube for further percutaneous clearance (0,05%). Major morbidity appeared in one patient consisting in biliary leakage and requiring reintervention (0,05%). Other major morbidity did not appear. 4 patients presented minor morbidity (14%). Median postoperative stay was 3 days. 11 patients were discharged before 24 hours (39%). No retained stones were documented. We used laser lithotripsy in 5 patients (18%). Conclusions: LCBDE is a safe and reproducible procedure, even in initial experience. Laser lithotripsy and a 3 mm choledoscope increase the global success rate allowing the trans-cystic approach in a considerable proportion of patients.
Wilson's disease (WD) is an autosomal recessive disorder characterized by copper overload. In thi... more Wilson's disease (WD) is an autosomal recessive disorder characterized by copper overload. In this disease, inadequate hepatic excretion leads to copper accumulation in the liver, brain, kidney, and cornea. Severe neurological symptoms can develop in patients with WD, often in the absence of relevant liver damage: it is unclear whether liver transplantation (LT) could reverse neurological symptoms, and at present LT is not recommended in this setting. We report a case of regression of neurological symptoms in a patient affected by WD with prevalent neurological involvement. A 19-year-old man with disabling neuropsychiatric symptoms from WD that included frontal ataxia, akinesia, dystonia, tremors, and behavioral disorders in the presence of preserved liver function (Model for End-Stage Liver Disease score ¼ 7; Child-Turcotte-Pugh score ¼ A5) underwent LT in November 2009. At the time of LT, encephalic magnetic resonance imaging (MRI) indicated diffuse neurodegenerative alterations involving subtentorial and supratentorial structures; bilateral Kayser-Fleischer ring was present. Four years after LT, laboratory tests show normalized copper metabolism and excellent liver function test results. Encephalic MRI shows a substantial improvement of already-known signal alterations at nuclei thalamus and putamen, mesencephalon, and pons. Kayser-Fleischer ring disappeared from the right eye, but a little remnant is still visible in the left eye. At neurological examination, all of the previous symptoms and signs are no longer present and behavioral disorders are no longer present; psychosocial functions are completely restored. The present case provides some evidence that LT may be a valid therapeutic option for WD patients with marked neurological impairment, particularly in those no longer responsive to chelation therapy.
There are no literature data on surgical problems that can be encountered during harvesting of gr... more There are no literature data on surgical problems that can be encountered during harvesting of grafts from elderly donors. The aim of our study was to report our experience during liver harvesting from donors over 70 years old and during transplantations of these grafts. From April 1986 to December 2001, 686 OLT in 599 patients were performed at the Liver Transplant Unit of the S. Orsola Hospital in Bologna. In particular we harvested 68 livers from donors with mean age of 75.4+/-4.5 years (range 70-87). The cause of brain death was a spontaneous cerebral haemorrhage in 58 cases and trauma in 10 cases. Thirteen donors were previously submitted to cardiovascular surgery. Three subjects had an abdominal aorta aneurysm 5, 6 and 7 cm large respectively, involving the iliac arteries, not diagnosed before the harvesting procedure. In 60 donors atherosclerosis was present. Out of 68 transplanted patients with donor over 70 years of age we observed 13 arterial complications (19.1%): 7 hepat...
Introduction. We aimed to analyze the influence of intraoperative blood transfusion on postoperat... more Introduction. We aimed to analyze the influence of intraoperative blood transfusion on postoperative complications and survival and to identify the preoperative variables associated with greater intraoperative bleeding. Materials and Methods. Thirty-one elective liver transplantations (OLT) without blood transfusion performed between 1986 and 2002 (group 1) were compared with 62 patients (group 2) who underwent elective OLT with intraoperative transfusion after matching for gender, disease severity, and chronology. Results. The hemoglobin and hematocrit values were significantly greater in group 1 compared to group 2. No significant differences were reported for the other parameters. In particular, the type of surgical technique had no influence on the blood requirement. As expected the nontransfused patients received less autologous packed red blood cells compared with the transfused patients. No differences were observed in either group for mean CIT, ICU and hospital stay, or acute rejection. A significant difference was observed in the number of postoperative infectious episodes, which was higher in group 2 (28 vs 5, P ϭ .01). Graft and patient survivals at 3 months and 5 years did not differ significantly between groups. Conclusions. OLT without blood transfusion may be achieved in the presence of good recipient conditions. Lower preoperative hemoglobin and hematocrit values were associated with greater intraoperative transfusions.
Although octogenarian livers have been transplanted successfully in elective settings, their safe... more Although octogenarian livers have been transplanted successfully in elective settings, their safety in the case of fulminant hepatic failure has not yet been reported. From November 1998 to June 2003, we transplanted 3 livers from 80-, 82-, and 86-year-old donors. The donors were hemodynamically stable with an intensive care unit stay ranging from 24-48 hours. Cold ischemia time was from 260 minutes to 526 minutes. Mild macrosteatosis was present in 2 donors. Donor and recipient characteristics as well as posttransplantation evolution were evaluated. Two cases had uneventful courses and all recipients are well at 39, 21, and 5 months, respectively. The second recipient underwent retransplantation at 15 days due to technical complications. Livers from octogenarian donors may be safely used in an emergency to save patients. Age does not represent a limit for individually assessed and highly selected donors.
Aim. The aim of present study was to assess the effect of Celsior as compared with University of ... more Aim. The aim of present study was to assess the effect of Celsior as compared with University of Wisconsin (UW) solution on immediate and long-term function of kidney transplants harvested from elderly donors. Methods. A prospective multicenter randomized study was designed to evaluate the efficacy of Celsior versus UW solution for the clinical preservation of the kidney. Fifty renal transplants were performed from donors over 60 years old. Twenty-five kidneys were stored in Celsior and 25 in UW solution. The groups were comparable with regard to donor and recipient characteristics. Renal function outcomes were compared by evaluating delayed graft function rates, daily urinary output, as well as the evolution of mean serum creatinine at 1, 3, 5, 7, and 15 days. Results. The warm ischemia time was 42.4 Ϯ 11 minutes among Celsior vs 46.9 Ϯ 17.9 minutes in the UW cohort (P ϭ NS). The cold ischemia time was 18 Ϯ 4.5 hours in Celsior and 19 Ϯ 6.5 hours in UW (P ϭ NS). Delayed graft function occurred in 48% of the Celsior group and in 52% of the UW group (P ϭ NS). Mean serum creatinine levels and mean daily urinary output were also similar. One-and 5-year graft survivals of kidneys preserved with Celsior were 91.8% and 79.3% compared with 96% and 87.4% for UW without any significant statistical difference. Conclusions. Our data show that the preservation of kidneys from elderly donors in Celsior solution is equivalent to that of UW solution.
There are few reports of combined heart and liver transplantation (CHLT) for familial amyloidotic... more There are few reports of combined heart and liver transplantation (CHLT) for familial amyloidotic polyneuropathy (FAP). The technique for the operation remains to be defined. Four CHLTs were performed for amyloidogenic transthyretin-related (variant Glu89Gln-ATTR Glu89Gln) cardiomyopathy in our center. Patients 1 and 4 had no serious involvement of other organs, whereas patients 2 and 3 had evident peripheral neuropathy and gastrointestinal motility alterations. Patient 3 also had high-grade orthostatic hypotension. All four patients underwent cardiac and sequential hepatic transplantation with organs procured from the same donor. Venovenous bypass was used in patients 1 and 4 who experienced uncomplicated procedures. The amyloidotic liver of patient 4 was successfully utilized for a domino procedure to treat a patient with hepatocellular carcinoma on cirrhosis. The cardiac performance of patients 1 and 4 remains normal; there has been no progression of amyloidosis at 42 and 1 months after transplantation. Patient 2 had no intraoperative complications but experienced postoperative bleeding, renal failure, sepsis, and heart failure, and finally died of multiorgan failure 2 months after transplant. In patient 3, right hemicolectomy was required intraoperatively due to intestinal ischemia, without significant hemodynamic instability, while extracardiac symptoms of amyloidosis gradually worsened postoperatively. In conclusion, CHLT for ATTR Glu89Gln may be performed even in patients with advanced disease. However, the most compromised patients are more likely to display intraoperative risks, postoperative complications, and worsening of extracardiac, extrahepatic symptoms.
Introduction. The shortage of donors has made it necessary to consider older subjects, those with... more Introduction. The shortage of donors has made it necessary to consider older subjects, those with mild or moderate steatosis, and those who are HBcAb-or hepatitis C virus (HCV)-positive as marginal donors. Materials and Methods. From April 1986 to January 2002, 690 orthotopic liver transplantations (OLTs) were performed in 603 patients. In this series we used 68 donors older than 70 years, 51 with steatosis (38 mild, 12 moderate, and 1 severe), 44 were HBcAb-positive and 6 were HCV-positive. Results. Of 68 grafts from donors older than 70 years, 65 were used as a first OLT. These grafts showed 3 PNF, 11 arterial complications, 12 re-OLTs, and 14 deaths with graft survival of 72.3% and 61.34% at 1 and 3 years, respectively. All patients who received the other 3 grafts, which were used for re-OLT, died between postoperative day 21 and 720. Among the 51 grafts with steatosis, we observed 2 PNF of those within the mild steatosis group and graft survival rates of 76.8% and 70.9% at 1 and 3 years, respectively. Forty-four grafts from HBcAb-positive subjects were used in 18 HBsAgnegative and 26 HBsAg-positive recipients. Among the untreated patient group, 1 patient demonstrated hepatitis B virus (HBV) reinfection and 1 patient had de-novo HBV. No reinfection or de novo infections were observed in the 13 patients treated with immunoglobulin or in the 19 patients treated with lamivudine plus immunoglobulin, or in the only patient treated with lamivudine. Graft survival rates were 64.1% and 54.7% at 1 and 3 years, respectively. Among who received 6 patients transplants from HCV-positive donors, we observed 1 recurrence of chronic hepatitis, 1 re-OLT for hepatic vein stenosis, and 1 PNF. Conclusion. Old donors, those with moderate steatosis, or those who are HBcAb-and HCV-positive can be safely used in selected recipients to reduce waiting list mortality.
The transjugular intrahepatic portosystemic shunt (TIPS) is an acceptable procedure that has prov... more 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.
The current therapy for hepatitis C recurrence after liver transplantation OLT is based on interf... more The current therapy for hepatitis C recurrence after liver transplantation OLT is based on interferon (IFN) and ribavirin (RBV) in monotherapy or combination. The rate of sustained virological response (SVR) varies between 10% and 45%. We have retrospectively analyzed factors that could predict SVR after antiviral therapy. We analyzed 42 patients who completed a cycle of therapy with natural or pegylated IFN plus RBV. There were 15 (35.7%) patients who obtained an SVR. The following factors were significantly associated with a lack of SVR: donor age >or=50 years (P = .046); donor body mass index (BMI) > 27 (P = .016); genotype 1 versus 2 to 3 (P = 0.010), aspartate transferase (AST) before therapy >or= 140 U/L (P = .046), alanine transferase before therapy >or= 280 U/L (P = .055), use of natural IFN versus pegylated IFN (P = .016). The only factors remaining after multivariate analysis were: donor BMI, AST before therapy and genotype. Our data confirmed that genotype 1 was associated with poorer outcomes; other additional parameters can influence the response to antiviral therapy.
Hemophilia B is a congenital recessive disorder caused by deficiency of coagulation factor IX (FI... more Hemophilia B is a congenital recessive disorder caused by deficiency of coagulation factor IX (FIX). Surgical procedures can be performed in patients with hemophilia using high-purity and/or recombinant FIX, which has been shown to be safe and effective in surgical hemostasis. Liver transplantation is the only potentially curative treatment available for these patients, providing a long-term phenotypic cure for hemophilia. End-stage liver disease together with hemophilia exposes patients to greater risks of bleeding complications during the perioperative period with consequent difficulties in managing coagulopathy. The limited experiences reported by different investigators and the various strategies for clotting factor replacement make it difficult to define a single approach with respect to the optimal dose and method of administering FIX to achieve perioperative hemostasis. The limits of plasma-based coagulation tests-prothrombin time, activated partial thromboplastin time-have made thromboelastography a valid alternative in this kind of surgery. It has been demonstrated to be a useful tool for real-time analysis of clot formation using a whole-blood assay format. Further, it accurately illustrates the clinical effects of procoagulant or anticoagulant interventions. In this article, we have described the usefulness of thromboelastography to monitor the ability of high-purity FIX supplementation to restore a normal coagulation state and to guide the perioperative administration of blood products in a successful orthotopic liver transplantation in a hemophilic patient with deficiencies of factors IX and X, presenting with hepatitis C virus-related cirrhosis and hepatocellular carcinoma.
P OSTOPERATIVE arterial and biliary complications contribute significantly to morbidity and morta... more P OSTOPERATIVE arterial and biliary complications contribute significantly to morbidity and mortality of liver transplant recipients. 1-3 Surgery remains the mainstay of therapy, however, the management of these complications requires a multidisciplinary approach in which interventional radiological techniques have made important progress. 4-8 The aim of the present study was to evaluate the role of mini-invasive treatment of hepatic artery stenosis (HAS) and biliary strictures (BS) in our over 13-year experience. MATERIALS AND METHODS From April 1986 to October 1999, 508 OLT were performed in 452 patients. Arterial complications were 38 of 508 (7.4%). A conventional arterial anastomosis was performed in 28 patients, an iliac artery graft was used in nine cases, and a vascular prosthesis was used in one patient. In the arterial complications group, HAS occurred in three patients (18.4%). The HAS was diagnosed by routine Doppler ultrasound within 1 month after OLT. Management was by percutaneous transluminal angioplasty (PTA) in two patients and PTA plus stent in one patient. A choledochocholedochostomy was performed in all patients. Biliary complications were 35 of 508 (6.8%). Biliary strictures occurred in 22 patients, with more anastomotic strictures (16 patients) than nonanastomotic strictures (six patients). Twelve liver transplant patients with BS underwent mini-invasive treatments: balloon dilation (n ϭ 4) and stent implantation (n ϭ 8).
Aims: Chronic renal failure (CRF) is a recognized complication of organ transplantation and sever... more Aims: Chronic renal failure (CRF) is a recognized complication of organ transplantation and several risk factors there exist, linked both to patients and the procedure, which can favor its development. The aim of this study was to assess the incidence of post-transplantation CRF in a population of liver transplanted patients and to investigate the presence of possible risk factors for developing renal dysfunction. Methods: We performed a retrospective study on the liver-transplanted patients referring to liver transplantation ambulatory of "Tor Vergata" University of Rome and investigated the incidence of CRF and eventual need for renal replacement therapy (RRT). Furthermore, we searched for some possible risk factors for CRF development, such as systemic hypertension (SH), dyslipidemia, Diabetes Mellitus (DM), HBV and HCV status and calcyneurin inhibitors therapy. Results: From 1992 to today, 261 ortotopic liver transplantation have been performed at our Centre. In the post-transplantation period, 22 patients (8,4 %) developed chronic renal failure and were treated with standard intermittent hemodialysis (for a men time of 3 weeks). Among these, four male patients and one female subject have developed end stage renal disease (ESRD) and at present need chronic RRT. Further data about ESRD patients are reported in the Table below. One of them has died for cardiovascular complications during dialytic session. Among the remaining 17 patients, 5 subjects (29,5%) were HCV positive, 9/17 (52,9%) showed SH, 2/17 (11,8%) showed DM and 10/17 (58,8%) were treated with CsA. They partially recovered their renal function and are at present under conservative therapy. Conclusions: CRF proved to be a relatively common complication in our liver transplanted patients, confirming data reported in literature. Risk factors for developing renal dysfunction present in our patients are also cardiovascular risk factors and this could lead to an increase in mortality for cardiovascular pathology, particularly incident in uremic patients. It could be useful to pay attention to pretransplant renal dysfunction, modifiable cardiovascular risk factors and immunosuppressant protocol in order to avoid CRF onset in liver transplanted patients, thus obtaining a reduction of morbidity and mortality and of the costs for the National Sanitary System.
Background. Optimization of the conditions for regeneration is a major goal in the management of ... more Background. Optimization of the conditions for regeneration is a major goal in the management of patients with acute liver failure (ALF). Previous observations suggested that hyperoxygenation of the liver may improve its regenerative capacity. Thus, this study aimed to determine whether an additional supply of oxygenated blood achieved by portal vein arterialization (PVA) is protective in rat ALF caused by toxin administration or hepatectomy. Methods. Sprague-Dawley rats were subjected or not to PVA after CCl 4 intoxication or extended hepatectomy. PVA was performed by interposing a stent between the left renal artery and splenic vein after left nephrectomy and splenectomy. Liver injury was evaluated by the serum ALT level and necrotic cell count. Hepatocyte regeneration was assessed by calculating the mitotic index and bromodeoxyuridine (BrdU) staining. The 10-day survival was assessed in separate experimental groups. Results. The pO 2 in portal blood increased significantly following PVA. In the CCl 4-induced ALF, serum ALT levels and necrosis were significantly reduced in arterialized than non-arterialized rats. PVA greatly promotes liver regeneration in both models. Finally, PVA significantly improved survival compared to controls (CCl 4 : 100 versus 40%; 90% hepatectomy: 90 versus 30%). Interestingly, in the CCl 4-induced ALF, survival was 100% even when the shunt was closed after 48 h. Conclusion. These data indicate that the additional supply of arterial oxygenated blood through PVA promotes a rapid regeneration leading to the resolution of toxic-induced massive liver necrosis and a faster restoration of liver mass after partial hepatectomy in rats. Thus, PVA may represent a novel tool for optimizing hepatocyte regeneration.
Background and aim: The role of oral. supplementation with branchedchain amino acids (BCAA) in pa... more Background and aim: The role of oral. supplementation with branchedchain amino acids (BCAA) in patients with advanced cirrhosis is not settled. Nutritional approach might prevent progressive liver cell failure, improve nntritional parameters and quality of life of cirrhotic patients. Materials and methods: A multicenter, double-blind study comparing 1-year BCAA supplements (14.4 g/day, 59 cases) with equinitrogenousequicaloric lactoalbumin (L-ALB, n = 56) or simply equicaloric maltodextrins (M-DXT, n = 59) was carried out in advanced cirrhosis. Primary outcomes were prevention of liver cell failure (death or deterioration to exclusion criteria), need for hospital admission and duration of hospital stay. Secondary outcomes were nutritional parameters, laboratory data and Child-Pugh score, anorexia and healthrelated quality of life, and need for therapy. Results: 43 events were recorded in 1809 patieot/months (657 on BCAA, 551 on L-ALB and 601 on M-DXT). BCAA treatment significantly reduced the event rate compared with L-ALB: (OR, 0.43; 95% Confidence Interval, 0.19-0.96; Logrank Mantel-Cox, P = 0.039) and non-significantly compared with M-DXT (OR, 0.52; 95% CI, 0.23-1.17; P = 0.108). The average admission rate was 0.6-2_ SE 0.2 patient/year in the BCAA arm, 2.1-+ 0.5 in L-ALB, and 1.9 ± 0.4 in M-DXT (P vs. BCAA: = 0.006 and = 0.003, respectivuly). While in the study, BCAA-treated patients spent 195 days in hospital, patients on L-ALB 327 days, and patients on M-DXT 520 days (P = 0.038, Kruskal-Wallis test). In patients who remained in the study there was a general trend towards improved nutritional parameters with BCAA. The Child-Pugh score decreased in the BCAA arm ((from 9.1 +_ 0,3 to 7.9-+ 0.3, P < 0.0001), and the time course was different from that observed in the 2 control arms (Repeated measures ANOVA, P = 0.013). Also anorexia and health-related quality of life (Short Form-36 questionnaire) improved. A poor compliance to BCAA was observed in the long-term. Conclusion: In advanced cirrhosis BCAA supplements are better than equicaloric, equinitrogenous supplements with regard to prevention of liver cell failure and death, hospital admission rates and secondary outcomes, including oerceived health status.
Survival rates of patients with acute liver failure (ALF) without transplantation are poor. Howev... more Survival rates of patients with acute liver failure (ALF) without transplantation are poor. However, many of them die awaiting a transplant because of the donor organ shortage. Supporting these patients until an organ becomes available or until their own liver is able to regenerate itself thus avoiding transplantation is a major goal in their multidisciplinary treatment. Animal experimental studies have shown that portal vein arterialization (PVA) enhances the regenerative capacity of hepatocytes by increasing the oxygen supply to the liver after extended hepatectomy or in toxin-induced ALF models. Furthermore, we have reported the application of PVA in patients with ALF. We herein have described the technical aspects of the PVA procedure both in preclinical models and in man.
Background Laparoscopic liver resection for hepatocellular carcinoma (HCC) in Child–Pugh A cirrho... more Background Laparoscopic liver resection for hepatocellular carcinoma (HCC) in Child–Pugh A cirrhosis has been demonstrated as beneficial. However, the role of laparoscopy in Child–Pugh B cirrhosis is undetermined. The aim of this retrospective cohort study was to compare open and laparoscopic resection for HCC with Child–Pugh B cirrhosis. Methods Data on liver resections were gathered from 17 centres. A 1 : 1 propensity score matching was performed according to 17 predefined variables. Results Of 382 available liver resections, 100 laparoscopic and 100 open resections were matched and analysed. The 90-day postoperative mortality rate was similar in open and laparoscopic groups (4.0 versus 2.0 per cent respectively; P = 0.687). Laparoscopy was associated with lower blood loss (median 110 ml versus 400 ml in the open group; P = 0.004), less morbidity (38.0 versus 51.0 per cent respectively; P = 0.041) and fewer major complications (7.0 versus 21.0 per cent; P = 0.010), and ascites was...
Background: Hepatoblastoma (HB) is the most common malignant liver tumour in children; it account... more Background: Hepatoblastoma (HB) is the most common malignant liver tumour in children; it accounts for 50% of liver tumours and 1.3% of malignant tumours in childhood. Surgical resection remains the cornerstone of curative therapy. Methods: Retrospective review of patients diagnosed of HB in the last 15 years in our centre and review of literature. Results: 5 patients were identified. Male: 100%. Mean age: 3.15 years-old. Low birth weight: 0. Tumour biopsy: 100%. a-fetoprotein (a FP) < 100 ng/mL: 20%; the same patient was initially diagnosed of metastases (lungs, bilateral) and finally died. Chemotherapy regimens: SIOPEL 3 (PLADO): 60%, SIOPEL 4: 20%, SIOPEL 6: 20%. Mean time diagnostic-surgery: 96.26 days. Staging CT post neoadjuvant chemotherapy: 100%. Types of surgery performed: right hepatectomy 60%, left hepatectomy 20%, transverse hepatectomy 20%. Postoperative complications: Clavien-Dindo grade II: 80%, grade III: 20%. Free surgical margins: 80%. Histology: epithelial 60%; mixed epithelialsarcomatous 20%; mixed epithelial-mesenchymal 20%. Portal, suprahepatic or extrahepatic intraabdominal disease were not observed. Mean disease free survival: 9.19 years. Mortality: 20%. Conclusion: HB is the most frequent malignant liver tumour in children. Low a FP (< 100 ng/mL) and the presence of metastases initially diagnosed worsen prognosis. Neoadjuvant chemotherapy may lead to downstage tumour size and ease surgery, even though surgery is the only curative therapy.
choledocotomy was performed in 7 patients (25%). Primary or T-Tube choledocorraphy was performed ... more choledocotomy was performed in 7 patients (25%). Primary or T-Tube choledocorraphy was performed in 5 (18%) and 2 patients (0,07%) respectively. The procedure was successful in 27 patients (96%). Due to hemodynamic instability, the procedure was finished prematurely in 1 patient leaving one stone and placing a T-Tube for further percutaneous clearance (0,05%). Major morbidity appeared in one patient consisting in biliary leakage and requiring reintervention (0,05%). Other major morbidity did not appear. 4 patients presented minor morbidity (14%). Median postoperative stay was 3 days. 11 patients were discharged before 24 hours (39%). No retained stones were documented. We used laser lithotripsy in 5 patients (18%). Conclusions: LCBDE is a safe and reproducible procedure, even in initial experience. Laser lithotripsy and a 3 mm choledoscope increase the global success rate allowing the trans-cystic approach in a considerable proportion of patients.
Wilson's disease (WD) is an autosomal recessive disorder characterized by copper overload. In thi... more Wilson's disease (WD) is an autosomal recessive disorder characterized by copper overload. In this disease, inadequate hepatic excretion leads to copper accumulation in the liver, brain, kidney, and cornea. Severe neurological symptoms can develop in patients with WD, often in the absence of relevant liver damage: it is unclear whether liver transplantation (LT) could reverse neurological symptoms, and at present LT is not recommended in this setting. We report a case of regression of neurological symptoms in a patient affected by WD with prevalent neurological involvement. A 19-year-old man with disabling neuropsychiatric symptoms from WD that included frontal ataxia, akinesia, dystonia, tremors, and behavioral disorders in the presence of preserved liver function (Model for End-Stage Liver Disease score ¼ 7; Child-Turcotte-Pugh score ¼ A5) underwent LT in November 2009. At the time of LT, encephalic magnetic resonance imaging (MRI) indicated diffuse neurodegenerative alterations involving subtentorial and supratentorial structures; bilateral Kayser-Fleischer ring was present. Four years after LT, laboratory tests show normalized copper metabolism and excellent liver function test results. Encephalic MRI shows a substantial improvement of already-known signal alterations at nuclei thalamus and putamen, mesencephalon, and pons. Kayser-Fleischer ring disappeared from the right eye, but a little remnant is still visible in the left eye. At neurological examination, all of the previous symptoms and signs are no longer present and behavioral disorders are no longer present; psychosocial functions are completely restored. The present case provides some evidence that LT may be a valid therapeutic option for WD patients with marked neurological impairment, particularly in those no longer responsive to chelation therapy.
There are no literature data on surgical problems that can be encountered during harvesting of gr... more There are no literature data on surgical problems that can be encountered during harvesting of grafts from elderly donors. The aim of our study was to report our experience during liver harvesting from donors over 70 years old and during transplantations of these grafts. From April 1986 to December 2001, 686 OLT in 599 patients were performed at the Liver Transplant Unit of the S. Orsola Hospital in Bologna. In particular we harvested 68 livers from donors with mean age of 75.4+/-4.5 years (range 70-87). The cause of brain death was a spontaneous cerebral haemorrhage in 58 cases and trauma in 10 cases. Thirteen donors were previously submitted to cardiovascular surgery. Three subjects had an abdominal aorta aneurysm 5, 6 and 7 cm large respectively, involving the iliac arteries, not diagnosed before the harvesting procedure. In 60 donors atherosclerosis was present. Out of 68 transplanted patients with donor over 70 years of age we observed 13 arterial complications (19.1%): 7 hepat...
Introduction. We aimed to analyze the influence of intraoperative blood transfusion on postoperat... more Introduction. We aimed to analyze the influence of intraoperative blood transfusion on postoperative complications and survival and to identify the preoperative variables associated with greater intraoperative bleeding. Materials and Methods. Thirty-one elective liver transplantations (OLT) without blood transfusion performed between 1986 and 2002 (group 1) were compared with 62 patients (group 2) who underwent elective OLT with intraoperative transfusion after matching for gender, disease severity, and chronology. Results. The hemoglobin and hematocrit values were significantly greater in group 1 compared to group 2. No significant differences were reported for the other parameters. In particular, the type of surgical technique had no influence on the blood requirement. As expected the nontransfused patients received less autologous packed red blood cells compared with the transfused patients. No differences were observed in either group for mean CIT, ICU and hospital stay, or acute rejection. A significant difference was observed in the number of postoperative infectious episodes, which was higher in group 2 (28 vs 5, P ϭ .01). Graft and patient survivals at 3 months and 5 years did not differ significantly between groups. Conclusions. OLT without blood transfusion may be achieved in the presence of good recipient conditions. Lower preoperative hemoglobin and hematocrit values were associated with greater intraoperative transfusions.
Although octogenarian livers have been transplanted successfully in elective settings, their safe... more Although octogenarian livers have been transplanted successfully in elective settings, their safety in the case of fulminant hepatic failure has not yet been reported. From November 1998 to June 2003, we transplanted 3 livers from 80-, 82-, and 86-year-old donors. The donors were hemodynamically stable with an intensive care unit stay ranging from 24-48 hours. Cold ischemia time was from 260 minutes to 526 minutes. Mild macrosteatosis was present in 2 donors. Donor and recipient characteristics as well as posttransplantation evolution were evaluated. Two cases had uneventful courses and all recipients are well at 39, 21, and 5 months, respectively. The second recipient underwent retransplantation at 15 days due to technical complications. Livers from octogenarian donors may be safely used in an emergency to save patients. Age does not represent a limit for individually assessed and highly selected donors.
Aim. The aim of present study was to assess the effect of Celsior as compared with University of ... more Aim. The aim of present study was to assess the effect of Celsior as compared with University of Wisconsin (UW) solution on immediate and long-term function of kidney transplants harvested from elderly donors. Methods. A prospective multicenter randomized study was designed to evaluate the efficacy of Celsior versus UW solution for the clinical preservation of the kidney. Fifty renal transplants were performed from donors over 60 years old. Twenty-five kidneys were stored in Celsior and 25 in UW solution. The groups were comparable with regard to donor and recipient characteristics. Renal function outcomes were compared by evaluating delayed graft function rates, daily urinary output, as well as the evolution of mean serum creatinine at 1, 3, 5, 7, and 15 days. Results. The warm ischemia time was 42.4 Ϯ 11 minutes among Celsior vs 46.9 Ϯ 17.9 minutes in the UW cohort (P ϭ NS). The cold ischemia time was 18 Ϯ 4.5 hours in Celsior and 19 Ϯ 6.5 hours in UW (P ϭ NS). Delayed graft function occurred in 48% of the Celsior group and in 52% of the UW group (P ϭ NS). Mean serum creatinine levels and mean daily urinary output were also similar. One-and 5-year graft survivals of kidneys preserved with Celsior were 91.8% and 79.3% compared with 96% and 87.4% for UW without any significant statistical difference. Conclusions. Our data show that the preservation of kidneys from elderly donors in Celsior solution is equivalent to that of UW solution.
There are few reports of combined heart and liver transplantation (CHLT) for familial amyloidotic... more There are few reports of combined heart and liver transplantation (CHLT) for familial amyloidotic polyneuropathy (FAP). The technique for the operation remains to be defined. Four CHLTs were performed for amyloidogenic transthyretin-related (variant Glu89Gln-ATTR Glu89Gln) cardiomyopathy in our center. Patients 1 and 4 had no serious involvement of other organs, whereas patients 2 and 3 had evident peripheral neuropathy and gastrointestinal motility alterations. Patient 3 also had high-grade orthostatic hypotension. All four patients underwent cardiac and sequential hepatic transplantation with organs procured from the same donor. Venovenous bypass was used in patients 1 and 4 who experienced uncomplicated procedures. The amyloidotic liver of patient 4 was successfully utilized for a domino procedure to treat a patient with hepatocellular carcinoma on cirrhosis. The cardiac performance of patients 1 and 4 remains normal; there has been no progression of amyloidosis at 42 and 1 months after transplantation. Patient 2 had no intraoperative complications but experienced postoperative bleeding, renal failure, sepsis, and heart failure, and finally died of multiorgan failure 2 months after transplant. In patient 3, right hemicolectomy was required intraoperatively due to intestinal ischemia, without significant hemodynamic instability, while extracardiac symptoms of amyloidosis gradually worsened postoperatively. In conclusion, CHLT for ATTR Glu89Gln may be performed even in patients with advanced disease. However, the most compromised patients are more likely to display intraoperative risks, postoperative complications, and worsening of extracardiac, extrahepatic symptoms.
Introduction. The shortage of donors has made it necessary to consider older subjects, those with... more Introduction. The shortage of donors has made it necessary to consider older subjects, those with mild or moderate steatosis, and those who are HBcAb-or hepatitis C virus (HCV)-positive as marginal donors. Materials and Methods. From April 1986 to January 2002, 690 orthotopic liver transplantations (OLTs) were performed in 603 patients. In this series we used 68 donors older than 70 years, 51 with steatosis (38 mild, 12 moderate, and 1 severe), 44 were HBcAb-positive and 6 were HCV-positive. Results. Of 68 grafts from donors older than 70 years, 65 were used as a first OLT. These grafts showed 3 PNF, 11 arterial complications, 12 re-OLTs, and 14 deaths with graft survival of 72.3% and 61.34% at 1 and 3 years, respectively. All patients who received the other 3 grafts, which were used for re-OLT, died between postoperative day 21 and 720. Among the 51 grafts with steatosis, we observed 2 PNF of those within the mild steatosis group and graft survival rates of 76.8% and 70.9% at 1 and 3 years, respectively. Forty-four grafts from HBcAb-positive subjects were used in 18 HBsAgnegative and 26 HBsAg-positive recipients. Among the untreated patient group, 1 patient demonstrated hepatitis B virus (HBV) reinfection and 1 patient had de-novo HBV. No reinfection or de novo infections were observed in the 13 patients treated with immunoglobulin or in the 19 patients treated with lamivudine plus immunoglobulin, or in the only patient treated with lamivudine. Graft survival rates were 64.1% and 54.7% at 1 and 3 years, respectively. Among who received 6 patients transplants from HCV-positive donors, we observed 1 recurrence of chronic hepatitis, 1 re-OLT for hepatic vein stenosis, and 1 PNF. Conclusion. Old donors, those with moderate steatosis, or those who are HBcAb-and HCV-positive can be safely used in selected recipients to reduce waiting list mortality.
The transjugular intrahepatic portosystemic shunt (TIPS) is an acceptable procedure that has prov... more 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.
The current therapy for hepatitis C recurrence after liver transplantation OLT is based on interf... more The current therapy for hepatitis C recurrence after liver transplantation OLT is based on interferon (IFN) and ribavirin (RBV) in monotherapy or combination. The rate of sustained virological response (SVR) varies between 10% and 45%. We have retrospectively analyzed factors that could predict SVR after antiviral therapy. We analyzed 42 patients who completed a cycle of therapy with natural or pegylated IFN plus RBV. There were 15 (35.7%) patients who obtained an SVR. The following factors were significantly associated with a lack of SVR: donor age &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;or=50 years (P = .046); donor body mass index (BMI) &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; 27 (P = .016); genotype 1 versus 2 to 3 (P = 0.010), aspartate transferase (AST) before therapy &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;or= 140 U/L (P = .046), alanine transferase before therapy &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;or= 280 U/L (P = .055), use of natural IFN versus pegylated IFN (P = .016). The only factors remaining after multivariate analysis were: donor BMI, AST before therapy and genotype. Our data confirmed that genotype 1 was associated with poorer outcomes; other additional parameters can influence the response to antiviral therapy.
Hemophilia B is a congenital recessive disorder caused by deficiency of coagulation factor IX (FI... more Hemophilia B is a congenital recessive disorder caused by deficiency of coagulation factor IX (FIX). Surgical procedures can be performed in patients with hemophilia using high-purity and/or recombinant FIX, which has been shown to be safe and effective in surgical hemostasis. Liver transplantation is the only potentially curative treatment available for these patients, providing a long-term phenotypic cure for hemophilia. End-stage liver disease together with hemophilia exposes patients to greater risks of bleeding complications during the perioperative period with consequent difficulties in managing coagulopathy. The limited experiences reported by different investigators and the various strategies for clotting factor replacement make it difficult to define a single approach with respect to the optimal dose and method of administering FIX to achieve perioperative hemostasis. The limits of plasma-based coagulation tests-prothrombin time, activated partial thromboplastin time-have made thromboelastography a valid alternative in this kind of surgery. It has been demonstrated to be a useful tool for real-time analysis of clot formation using a whole-blood assay format. Further, it accurately illustrates the clinical effects of procoagulant or anticoagulant interventions. In this article, we have described the usefulness of thromboelastography to monitor the ability of high-purity FIX supplementation to restore a normal coagulation state and to guide the perioperative administration of blood products in a successful orthotopic liver transplantation in a hemophilic patient with deficiencies of factors IX and X, presenting with hepatitis C virus-related cirrhosis and hepatocellular carcinoma.
P OSTOPERATIVE arterial and biliary complications contribute significantly to morbidity and morta... more P OSTOPERATIVE arterial and biliary complications contribute significantly to morbidity and mortality of liver transplant recipients. 1-3 Surgery remains the mainstay of therapy, however, the management of these complications requires a multidisciplinary approach in which interventional radiological techniques have made important progress. 4-8 The aim of the present study was to evaluate the role of mini-invasive treatment of hepatic artery stenosis (HAS) and biliary strictures (BS) in our over 13-year experience. MATERIALS AND METHODS From April 1986 to October 1999, 508 OLT were performed in 452 patients. Arterial complications were 38 of 508 (7.4%). A conventional arterial anastomosis was performed in 28 patients, an iliac artery graft was used in nine cases, and a vascular prosthesis was used in one patient. In the arterial complications group, HAS occurred in three patients (18.4%). The HAS was diagnosed by routine Doppler ultrasound within 1 month after OLT. Management was by percutaneous transluminal angioplasty (PTA) in two patients and PTA plus stent in one patient. A choledochocholedochostomy was performed in all patients. Biliary complications were 35 of 508 (6.8%). Biliary strictures occurred in 22 patients, with more anastomotic strictures (16 patients) than nonanastomotic strictures (six patients). Twelve liver transplant patients with BS underwent mini-invasive treatments: balloon dilation (n ϭ 4) and stent implantation (n ϭ 8).
Aims: Chronic renal failure (CRF) is a recognized complication of organ transplantation and sever... more Aims: Chronic renal failure (CRF) is a recognized complication of organ transplantation and several risk factors there exist, linked both to patients and the procedure, which can favor its development. The aim of this study was to assess the incidence of post-transplantation CRF in a population of liver transplanted patients and to investigate the presence of possible risk factors for developing renal dysfunction. Methods: We performed a retrospective study on the liver-transplanted patients referring to liver transplantation ambulatory of "Tor Vergata" University of Rome and investigated the incidence of CRF and eventual need for renal replacement therapy (RRT). Furthermore, we searched for some possible risk factors for CRF development, such as systemic hypertension (SH), dyslipidemia, Diabetes Mellitus (DM), HBV and HCV status and calcyneurin inhibitors therapy. Results: From 1992 to today, 261 ortotopic liver transplantation have been performed at our Centre. In the post-transplantation period, 22 patients (8,4 %) developed chronic renal failure and were treated with standard intermittent hemodialysis (for a men time of 3 weeks). Among these, four male patients and one female subject have developed end stage renal disease (ESRD) and at present need chronic RRT. Further data about ESRD patients are reported in the Table below. One of them has died for cardiovascular complications during dialytic session. Among the remaining 17 patients, 5 subjects (29,5%) were HCV positive, 9/17 (52,9%) showed SH, 2/17 (11,8%) showed DM and 10/17 (58,8%) were treated with CsA. They partially recovered their renal function and are at present under conservative therapy. Conclusions: CRF proved to be a relatively common complication in our liver transplanted patients, confirming data reported in literature. Risk factors for developing renal dysfunction present in our patients are also cardiovascular risk factors and this could lead to an increase in mortality for cardiovascular pathology, particularly incident in uremic patients. It could be useful to pay attention to pretransplant renal dysfunction, modifiable cardiovascular risk factors and immunosuppressant protocol in order to avoid CRF onset in liver transplanted patients, thus obtaining a reduction of morbidity and mortality and of the costs for the National Sanitary System.
Background. Optimization of the conditions for regeneration is a major goal in the management of ... more Background. Optimization of the conditions for regeneration is a major goal in the management of patients with acute liver failure (ALF). Previous observations suggested that hyperoxygenation of the liver may improve its regenerative capacity. Thus, this study aimed to determine whether an additional supply of oxygenated blood achieved by portal vein arterialization (PVA) is protective in rat ALF caused by toxin administration or hepatectomy. Methods. Sprague-Dawley rats were subjected or not to PVA after CCl 4 intoxication or extended hepatectomy. PVA was performed by interposing a stent between the left renal artery and splenic vein after left nephrectomy and splenectomy. Liver injury was evaluated by the serum ALT level and necrotic cell count. Hepatocyte regeneration was assessed by calculating the mitotic index and bromodeoxyuridine (BrdU) staining. The 10-day survival was assessed in separate experimental groups. Results. The pO 2 in portal blood increased significantly following PVA. In the CCl 4-induced ALF, serum ALT levels and necrosis were significantly reduced in arterialized than non-arterialized rats. PVA greatly promotes liver regeneration in both models. Finally, PVA significantly improved survival compared to controls (CCl 4 : 100 versus 40%; 90% hepatectomy: 90 versus 30%). Interestingly, in the CCl 4-induced ALF, survival was 100% even when the shunt was closed after 48 h. Conclusion. These data indicate that the additional supply of arterial oxygenated blood through PVA promotes a rapid regeneration leading to the resolution of toxic-induced massive liver necrosis and a faster restoration of liver mass after partial hepatectomy in rats. Thus, PVA may represent a novel tool for optimizing hepatocyte regeneration.
Background and aim: The role of oral. supplementation with branchedchain amino acids (BCAA) in pa... more Background and aim: The role of oral. supplementation with branchedchain amino acids (BCAA) in patients with advanced cirrhosis is not settled. Nutritional approach might prevent progressive liver cell failure, improve nntritional parameters and quality of life of cirrhotic patients. Materials and methods: A multicenter, double-blind study comparing 1-year BCAA supplements (14.4 g/day, 59 cases) with equinitrogenousequicaloric lactoalbumin (L-ALB, n = 56) or simply equicaloric maltodextrins (M-DXT, n = 59) was carried out in advanced cirrhosis. Primary outcomes were prevention of liver cell failure (death or deterioration to exclusion criteria), need for hospital admission and duration of hospital stay. Secondary outcomes were nutritional parameters, laboratory data and Child-Pugh score, anorexia and healthrelated quality of life, and need for therapy. Results: 43 events were recorded in 1809 patieot/months (657 on BCAA, 551 on L-ALB and 601 on M-DXT). BCAA treatment significantly reduced the event rate compared with L-ALB: (OR, 0.43; 95% Confidence Interval, 0.19-0.96; Logrank Mantel-Cox, P = 0.039) and non-significantly compared with M-DXT (OR, 0.52; 95% CI, 0.23-1.17; P = 0.108). The average admission rate was 0.6-2_ SE 0.2 patient/year in the BCAA arm, 2.1-+ 0.5 in L-ALB, and 1.9 ± 0.4 in M-DXT (P vs. BCAA: = 0.006 and = 0.003, respectivuly). While in the study, BCAA-treated patients spent 195 days in hospital, patients on L-ALB 327 days, and patients on M-DXT 520 days (P = 0.038, Kruskal-Wallis test). In patients who remained in the study there was a general trend towards improved nutritional parameters with BCAA. The Child-Pugh score decreased in the BCAA arm ((from 9.1 +_ 0,3 to 7.9-+ 0.3, P < 0.0001), and the time course was different from that observed in the 2 control arms (Repeated measures ANOVA, P = 0.013). Also anorexia and health-related quality of life (Short Form-36 questionnaire) improved. A poor compliance to BCAA was observed in the long-term. Conclusion: In advanced cirrhosis BCAA supplements are better than equicaloric, equinitrogenous supplements with regard to prevention of liver cell failure and death, hospital admission rates and secondary outcomes, including oerceived health status.
Survival rates of patients with acute liver failure (ALF) without transplantation are poor. Howev... more Survival rates of patients with acute liver failure (ALF) without transplantation are poor. However, many of them die awaiting a transplant because of the donor organ shortage. Supporting these patients until an organ becomes available or until their own liver is able to regenerate itself thus avoiding transplantation is a major goal in their multidisciplinary treatment. Animal experimental studies have shown that portal vein arterialization (PVA) enhances the regenerative capacity of hepatocytes by increasing the oxygen supply to the liver after extended hepatectomy or in toxin-induced ALF models. Furthermore, we have reported the application of PVA in patients with ALF. We herein have described the technical aspects of the PVA procedure both in preclinical models and in man.
Background Laparoscopic liver resection for hepatocellular carcinoma (HCC) in Child–Pugh A cirrho... more Background Laparoscopic liver resection for hepatocellular carcinoma (HCC) in Child–Pugh A cirrhosis has been demonstrated as beneficial. However, the role of laparoscopy in Child–Pugh B cirrhosis is undetermined. The aim of this retrospective cohort study was to compare open and laparoscopic resection for HCC with Child–Pugh B cirrhosis. Methods Data on liver resections were gathered from 17 centres. A 1 : 1 propensity score matching was performed according to 17 predefined variables. Results Of 382 available liver resections, 100 laparoscopic and 100 open resections were matched and analysed. The 90-day postoperative mortality rate was similar in open and laparoscopic groups (4.0 versus 2.0 per cent respectively; P = 0.687). Laparoscopy was associated with lower blood loss (median 110 ml versus 400 ml in the open group; P = 0.004), less morbidity (38.0 versus 51.0 per cent respectively; P = 0.041) and fewer major complications (7.0 versus 21.0 per cent; P = 0.010), and ascites was...
Background: Hepatoblastoma (HB) is the most common malignant liver tumour in children; it account... more Background: Hepatoblastoma (HB) is the most common malignant liver tumour in children; it accounts for 50% of liver tumours and 1.3% of malignant tumours in childhood. Surgical resection remains the cornerstone of curative therapy. Methods: Retrospective review of patients diagnosed of HB in the last 15 years in our centre and review of literature. Results: 5 patients were identified. Male: 100%. Mean age: 3.15 years-old. Low birth weight: 0. Tumour biopsy: 100%. a-fetoprotein (a FP) < 100 ng/mL: 20%; the same patient was initially diagnosed of metastases (lungs, bilateral) and finally died. Chemotherapy regimens: SIOPEL 3 (PLADO): 60%, SIOPEL 4: 20%, SIOPEL 6: 20%. Mean time diagnostic-surgery: 96.26 days. Staging CT post neoadjuvant chemotherapy: 100%. Types of surgery performed: right hepatectomy 60%, left hepatectomy 20%, transverse hepatectomy 20%. Postoperative complications: Clavien-Dindo grade II: 80%, grade III: 20%. Free surgical margins: 80%. Histology: epithelial 60%; mixed epithelialsarcomatous 20%; mixed epithelial-mesenchymal 20%. Portal, suprahepatic or extrahepatic intraabdominal disease were not observed. Mean disease free survival: 9.19 years. Mortality: 20%. Conclusion: HB is the most frequent malignant liver tumour in children. Low a FP (< 100 ng/mL) and the presence of metastases initially diagnosed worsen prognosis. Neoadjuvant chemotherapy may lead to downstage tumour size and ease surgery, even though surgery is the only curative therapy.
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Papers by R. Montalti