Gian Luigi Adani

Portal vein thrombosis after intraportal hepatocytes transplantation in a liver transplant recipient

Hepatocytes transplantation is viewed as a possible alternative or as a bridge therapy to liver transplantation for patients affected by acute or chronic liver disorders. Very few data regarding complications of hepatocytes transplantation is available from the literature. Herein we report for the first time a case of portal vein thrombosis after intraportal hepatocytes transplantation in a liver transplant recipient. A patient affected by acute graft dysfunction, not eligible for retransplantation, underwent intraportal infusion of 2 billion viable cryopreserved ABO identical human allogenic hepatocytes over a period of 5 h. Hepatocytes were transplanted at a concentration of 14 million/ml for a total infused volume of 280 ml. Doppler portal vein ultrasound and intraportal pressure were monitored during cell infusion. The procedure was complicated, 8 h after termination, by the development of portal vein thrombosis with liver failure and death of the patient. Autopsy showed occlusive thrombosis of the intrahepatic portal vein branches; cells or large aggregates of epithelial elements (polyclonal CEA positive), suggestive for transplanted hepatocytes, were co‐localized inside the thrombus.

Comparison of de novo tumours after liver transplantation with incidence rates from Italian cancer registries

AIM The purpose of this study is to describe de novo post-liver transplant malignancies and compare their frequency with incidence rates from Italian cancer registries. PATIENTS AND METHODS Four hundred and seventeen patients subjected to liver transplantation, from 1991 to 2005, surviving for at least 30 days and without a previous diagnosis of cancer (including hepatocellular carcinoma), were evaluated for the development of de novo malignancies excluding non-melanoma skin cancers. RESULTS During a total follow-up time of 2856 person-years, 43 de novo malignancies were diagnosed in 43 liver transplantation recipients (10.3%). The most common cancers were non-Hodgkin lymphoma (9 cases), cancer of the head and neck (8 cases), Kaposis sarcoma (6 cases) and esophageal carcinoma (5 cases). The 1, 3, 5 and 10 years estimated survival rates were 69%, 57%, 53% and 42%. Patients with de novo cancers had a lower 10-year survival rate than patients without cancers (58% versus 76%, p=0.005). The risk of cancer after liver transplantation was nearly 3-fold higher than that of the general population of the same age and sex (95% CI: 1.9-3.6). De novo tumour sites or types with significantly elevated SIR included Kaposis sarcoma (SIR=144), non-Hodgkin lymphoma (SIR=13.8), esophagus (SIR=23.4), head and neck cancers (SIR=7) and cervix uteri (SIR=30.7). CONCLUSIONS Tumours after liver transplantation are associated with lower long-term survival, confirming that cancer is a major cause of late mortality in liver transplantation.

Superiority of transplantation versus resection for the treatment of small hepatocellular carcinoma

The best therapy for hepatocellular carcinoma (HCC) is still debated. Hepatic resection (HR) is the treatment of choice for single HCC in Child A patients, whereas liver transplantation (LT) is usually reserved for Child B and C patients with single or multiple nodules. The aim of this study was to compare HR and LT for HCC within the Milan criteria on an intention‐to‐treat basis. Forty‐eight patients were treated by LT and 38 by HR. The median time on the waiting list for transplantation was 118 days. The estimated overall survival was significantly higher (P = 0.005) in the LT group than in the HR one. The estimated freedom from recurrence was also significantly higher (P < 0.0001) for LT patients than for HR ones. Indeed, the probability of HCC recurrence after resection was higher than after transplantation achieving 31% and 76% for HR and 2% and 2% for LT at 3 and 5 years after surgery. Multivariate analysis confirmed that transplantation was superior to resection in terms of patient’s survival and risk of HCC recurrence. We conclude that LT is superior to HR for small HCC in cirrhotic patients assuming that LT should be performed within 6–10 months after listing to reduce the dropouts for reasons of tumor progression.

STEATOSIS OF THE HEPATIC GRAFT AS A RISK FACTOR FOR POST-TRANSPLANT BILIARY COMPLICATIONS

Baccarani U, Isola M, Adani GL, Avellini C, Lorenzin D, Rossetto A, Currò G, Comuzzi C, Toniutto P, Risaliti A, Soldano F, Bresadola V, De Anna D, Bresadola F. Steatosis of the hepatic graft as a risk factor for post‐transplant biliary complications.
Clin Transplant 2009 DOI: 10.1111/j.1399‐0012.2009.01128.x.
© 2009 John Wiley & Sons A/S.

Percutaneous mechanical fragmentation and stent placement for the treatment of early posttransplantation portal vein thrombosis

BACKGROUND Early portal vein thrombosis is a rare but severe complication of liver transplantation requiring retransplantation or at least surgical thrombectomy, both hampered by high morbidity and mortality. METHODS We describe of a case of successful long-term recanalization of early posttransplantation portal vein thrombosis by a minimally invasive percutaneous transhepatic angiographic approach using both mechanical fragmentation and pharmacological lysis of the thrombus followed by stent placement. RESULTS Mechanical fragmentation and contemporaneous local urokinase administration resulted in complete removal of the clot; the use of a vascular stent after balloon dilatation allowed restoration of normal blood flow to the liver after 9 months of follow-up. CONCLUSIONS This case report confirms the possibility of successful recanalization of the portal vein after early posttransplantation thrombosis by a minimally invasive angiographic approach. Balloon dilatation and placement of a vascular stent could help to decrease the risk of recurrent thrombosis.

Percutaneous Transhepatic Portography for the Treatment of Early Portal Vein Thrombosis After Surgery

We treated three cases of early portal vein thrombosis (PVT) by minimally invasive percutaneous transhepatic portography. All patients developed PVT within 30 days of major hepatic surgery (one case each of orthotopic liver transplantation, splenectomy in a previous liver transplant recipient, and right extended hepatectomy with resection and reconstruction of the left branch of the portal vein for tumor infiltration). In all cases minimally invasive percutaneous transhepatic portography was adopted to treat this complication by mechanical fragmentation and pharmacological lysis of the thrombus. A vascular stent was also positioned in the two cases in which the thrombosis was related to a surgical technical problem. Mechanical fragmentation of the thrombus with contemporaneous local urokinase administration resulted in complete removal of the clot and allowed restoration of normal blood flow to the liver after a median follow-up of 37 months. PVT is an uncommon but severe complication after major surgery or liver transplantation. Surgical thrombectomy, with or without reconstruction of the portal vein, and retransplantation are characterized by important surgical morbidity and mortality. Based on our experience, minimally invasive percutaneous transhepatic portography should be considered an option toward successful recanalization of early PVT after major liver surgery including transplantation. Balloon dilatation and placement of a vascular stent could help to decrease the risk of recurrent thrombosis when a defective surgical technique is the reason for the thrombosis.

De Novo Tumors Are a Major Cause of Late Mortality After Orthotopic Liver Transplantation

The purpose of this study was to describe de novo post-orthotopic liver transplantation (OLT) malignancies for comparison with incidence rates in Italian cancer registries. Three hundred thirteen OLT patients engrafted from 1991 to 2006 and surviving 12 months without a previous diagnosis of cancer were evaluated for the development of de novo malignancies excluding nonmelanoma skin cancers. During a total follow-up time of 1753 PYs, 40 (12.8%) de novo malignancies were diagnosed in 40 recipients. The most common cancers were non-Hodgkin lymphoma (NHL; 20%), cancer of the head and neck (17%), Kaposi sarcoma (KS; 17%), and esophageal tumors (12%). The 1-, 3-, 5-, and 10-year estimated survival rates were 70%, 56%, 48%, and 39%. Patients with de novo cancers showed a lower 10-years survival rate (P = .0047) than patients without (39% vs 75%). The risk of cancer after OLT was 3-fold higher than that of the general population of the same age and gender (95% confidence interval [CI], 2.0-4.3). De novo tumor sites or types with significantly elevated standardized incidence ratios (SIRs) included KS (SIRs = 212), NHL (SIRs = 13.7), oesophagus (SIRs = 18.7), melanoma (SIRs = 10.1), and head and neck cancers (SIRs = 4.6). Tumors after OLT were associated with lower long-term survival, confirming that cancer is a major cause of late mortality.

Multicenter Italian Experience in Liver Transplantation for Hepatocellular Carcinoma in HIV-Infected Patients

BACKGROUND The aim of our work is to assess the clinical outcomes of liver transplantation (LT) for hepatocellular carcinoma (HCC) in HIV-coinfected patients. This is a multicenter study involving three Italian transplant centers in northern Italy: University of Modena, University of Bologna, and University of Udine. PATIENTS AND METHODS We compared 30 HIV-positive patients affected by HCC who underwent LT with 125 HIV-uninfected patients who received the same treatment from September 2004 to June 2009. At listing, there were no differences between HIV-infected and -uninfected patients regarding HCC features. Patients outside the University of California, San Francisco criteria (UCSF) were considered eligible for LT if a down-staging program permitted a reduction of tumor burden. RESULTS HIV-infected patients were younger, they were more frequently anti-HCV positive, and a higher number of HIV-infected patients presented a coinfection HBV-HCV. Pre-LT treatments (liver resection and or locoregional treatments) were similar between the two groups. Histological characteristics of the tumor were similar in patients with and without HIV infection. No differences were observed in terms of overall survival and HCC recurrence rates. CONCLUSION LT for HCC is a feasible procedure and the presence of HIV does not particularly affect the post-LT outcome.

Graft Loss Due to Percutaneous Sclerotherapy of a Lymphocele Using Acetic Acid After Renal Transplantation

Development of lymphoceles after renal transplantation is a well-described complication that occurs in up to 40% of recipients. The gold standard approach for the treatment of symptomatic cases is not well defined yet. Management options include simple aspiration, marsupialization by a laparotomy or laparoscopy, and percutaneous sclerotherapy using different chemical agents. Those approaches can be associated, and they depend on type, dimension, and localization of the lymphocele. Percutaneous sclerotherapy is considered to be less invasive than the surgical approach; it can be used safely and effectively, with low morbidity, in huge, rapidly accumulating lymphoceles. Moreover, this approach is highly successful, and the complication rate is acceptable; the major drawback is a recurrence rate close to 20%. We herewith report a renal transplant case in which the patient developed a symptomatic lymphocele that was initially treated by ultrasound-guided percutaneous sclerotherapy with ethanol and thereafter using acetic acid for early recurrence. A few hours after injection of acetic acid in the lymphatic cavity, the patient started to complain of acute pain localized to the renal graft and fever. An ultrasound of the abdomen revealed thrombosis of the renal vein and artery. The patient was immediately taken to the operating room, where the diagnosis of vascular thrombosis was confirmed and the graft was urgently explanted. In conclusion, we strongly suggest avoiding the use of acetic acid as a slerosating agent for the percutaneous treatment of post-renal transplant lymphocele because, based on our experience, it could be complicated by vascular thrombosis of the kidney, ending in graft loss.

Pharmacokinetic Interaction Between Everolimus and Antifungal Triazoles in a Liver Transplant Patient

Objective: TO describe the management of a pharmacokinetic interaction between azole antifungals (fluconazole and voriconazole) and everolimus in a patient who underwent an orthotopic liver transplant. Case Summary: A 65-year-old male who received an orthotopic liver transplant experienced an iatrogenic retroperitoneal duodenal perforation on postoperative day 55. His condition was subsequently complicated by severe sepsis and acute renal failure. Intravenous fluconazole 400 mg, followed by 100 mg every 24 hours according to impaired renal function, was immediately started; to avoid further nephrotoxicity, immunosuppressant therapy was switched from cyclosporine plus mycophenolate mofetil to oral everolimus 0.75 mg every 12 hours. Satisfactory steady-state minimum concentration (Cmin) of everolimus was achieved (∼5 ng/mL). On day 72 posttransplant, because of invasive aspergillosis, antifungal therapy was switched to intravenous voriconazole 400 mg every 12 hours on the first day, followed by 200 mg every 12 hours; to prevent drug toxicity, the everolimus dosage was promptly lowered to 0.25 mg every 24 hours. At that time, the everolimus Cmin averaged approximately 3 ng/mL. The concentration/dose ratio of everolimus (ie, Cmin reached at steady-state for each milligram per kilogram of drug administered) was markedly lower during fluconazole versus voriconazole cotreatment (mean ± SD, 3.49 ± 0.29 vs 11.05 ± 0.81 ng/mL per mg/kg/daily; p < 0.001). Despite intensive care, the patients condition continued to deteriorate and he died on day 84 posttransplant Discussion: Both azole antifungals were considered probable causative agents of an interaction with everolimus according to the Drug Interaction Probability Scale. The Interaction is due to the inhibition of CYP3A4–mediated everolimus clearance. Of note, prompt reduction of the everolimus dosage since the first azole coadministration, coupled with intensive therapeutic drug monitoring, represented a useful strategy to prevent drug overexposure. Conclusions: Our data suggest that during everolimus-azole cotreatment, a dose reduction of everolimus is needed to avoid overexposure. According to the different inhibitory potency of CYP3A4 activity, the reduction should be lower during fluconazole than during voriconazole cotreatment.