Vincenzo Scuderi

Bridging a patient with acute liver failure to liver transplantation by the AMC-bioartificial liver

Recently a phase I clinical trial has been started in Italy to bridge patients with acute liver failure (ALF) to orthotopic liver transplantation (OLT) by the AMC-bioartificial liver (AMC-BAL). The AMC-BAL is charged with 10 × 109 viable primary porcine hepatocytes isolated from a specified pathogen-free (SPF) pig. Here we report a patient with ALF due to acute HBV infection. This patient was treated for 35 h by two AMC-BAL treatments and was bridged to OLT. There was improvement of biochemical and clinical parameters during the treatment. No severe adverse events were observed during treatment and follow-up of 15 months after hospital discharge. Possible porcine endogenous retrovirus (PERV) activity could not be detected in the patients blood or blood cells up to 12 months after treatment.

Long‐term absence of porcine endogenous retrovirus infection in chronically immunosuppressed patients after treatment with the porcine cell–based Academic Medical Center bioartificial liver

Di Nicuolo G, D’Alessandro A, Andria B, Scuderi V, Scognamiglio M, Tammaro A, Mancini A, Cozzolino S, Di Florio E, Bracco A, Calise F, Chamuleau RAFM. Long‐term absence of porcine endogenous retrovirus infection in chronically immunosuppressed patients after treatment with the porcine cell–based Academic Medical Center bioartificial liver. Xenotransplantation 2010; 17: 431–439.

Liver Resection for Hepatocellular Carcinoma ≤3 cm: Results of an Italian Multicenter Study on 588 Patients

BACKGROUND The best treatment for patients with small hepatocellular carcinoma (S-HCC) is still controversial. The aim of this study was to evaluate operative and long-term results after liver resection (LR) for S-HCC, defined as tumor ≤3 cm. STUDY DESIGN Retrospective multicenter study of 588 LRs for S-HCC from 8 Italian hepatobiliary surgery units (years 1992 to 2008). Primary outcomes included operative risk. Logistic regression analysis was used to evaluate risk factors for postoperative mortality. Secondary outcomes were overall survival (OS) and disease-free survival (DFS), estimated by the Kaplan-Meier method. RESULTS Postoperative mortality was 1.9%, morbidity was 35.7% (major morbidity 7.3%), and blood transfusion rate was 13.8%. Child-Pugh class B and blood transfusions were associated with higher postoperative mortality. Rates of microvascular invasion and microsatellite nodules were 37.0% and 23.1%. After a median follow-up of 38.4 months, 5- and 10-year OS rates were 52.8% and 20.3%, with DFS of 32.4% and 21.7%. Local recurrence rate was 1.4%. Between the years 2000 and 2008, 5-year OS was significantly higher than that between the years 1992 and 1999 (61.9% vs 42.6%; p < 0.001). In multivariable analysis, Child-Pugh class B, portal hypertension, and microsatellite lesions were independently associated with poor OS. Microsatellite lesion was the only variable independently associated with poor DFS. CONCLUSIONS Liver resection for S-HCC has improved over the years, with decreased operative risk. Long-term survival after LR has increased. Despite small tumor size, rates of microsatellite nodules and microvascular invasion are not negligible. Presence of microsatellite lesions was the only variable identified as being associated with poor both OS and DFS.

Safety and efficacy of subcutaneous hepatitis B immunoglobulin after liver transplantation: an open single-arm prospective study.

Life‐long hepatitis B immunoglobulin (HBIG) administration is a main component of prophylactic strategy to prevent hepatitis B virus (HBV) reinfection after liver transplantation (LT). Long‐term effects of HBIG treatment are known only for intravenous (IV) and intramuscular formulations. To evaluate safety and efficacy of self‐administered SC HBIG, 135 LT patients receiving a 48‐week treatment were analyzed. The dose of HBIG was 500 IU or 1000 IU if body weight was <75 kg or ≥75 kg, respectively. Patients were switched from the monthly IV HBIG treatment to weekly SC HBIG 2–3 weeks after the last IV dosage. All patients were able to SC self‐injection after a single training. The treatment was effective in maintaining trough anti‐HBs levels >100 IU/L. No severe drug‐related side effects occurred. Fifteen injection‐site small hematomas and four cases of mild itch occurred. At the end of the study, anti‐HBs median titer was 232 IU/L (115–566 IU/L) and 97.8% of patients had an anti‐HBs level >150 IU/L. Due to high mean level of anti‐HBs titers observed during this study, individualized treatment schedules should be further investigated. In conclusion, SC HBIG for long‐term prophylaxis of post‐LT HBV reinfection resulted safe, well accepted, and effective in maintaining adequate anti‐HBs levels.

The single surgeon learning curve of laparoscopic liver resection: A continuous evolving process through stepwise difficulties

Abstract The aim of the study was to evaluate the single-surgeon learning curve (SSLC) in laparoscopic liver surgery over an 11-year period with risk-adjusted (RA) cumulative sum control chart analysis. Laparoscopic liver resection (LLR) is a challenging and highly demanding procedure. No specific data are available for defining the feasibility and reproducibility of the SSLC regarding a consistent and consecutive caseload volume over a specified time period. A total of 319 LLR performed by a single surgeon between June 2003 and May 2014 were retrospectively analyzed. A difficulty scale (DS) ranging from 1 to 10 was created to rate the technical difficulty of each LLR. The risk-adjusted cumulative sum control chart (RA-CUSUM) analysis evaluated conversion rate (CR), operative time (OT) and blood loss (BL). Perioperative morbidity and mortality were also analyzed. The RA-CUSUM analysis of the DS identified 3 different periods: P1 (n = 91 cases), with a mean DS of 3.8; P2 (cases 92–159), with a mean DS of 5.3; and P3 (cases 160–319), with a mean DS of 4.7. P2 presented the highest conversion and morbidity rates with a longer OT, whereas P3 showed the best results (P < 0.001). Fifty cases were needed to achieve a significant decrease in BL. The overall morbidity rate was 13.8%; no perioperative mortality was observed. According to our analysis, at least 160 cases (P3) are needed to complete the SSLC performing safely different types of LLR. A minimum of 50 cases can provide a significant decrease in BL. Based on these findings, a longer learning curve should be anticipated to broaden the indications for LLR.

Liver transplantation for adenomatosis: European experience

The aim of this study was to collect data from patients who underwent liver transplantation (LT) for adenomatosis; to analyze the symptoms, the characteristics of the disease, and the recipient outcomes; and to better define the role of LT in this rare indication. This retrospective multicenter study, based on data from the European Liver Transplant Registry, encompassed patients who underwent LT for adenomatosis between January 1, 1986, and July 15, 2013, in Europe. Patients with glycogen storage disease (GSD) type IA were not excluded. This study included 49 patients. Sixteen patients had GSD, and 7 had liver vascular abnormalities. The main indications for transplantation were either a suspicion of hepatocellular carcinoma (HCC; 15 patients) or a histologically proven HCC (16 patients), but only 17 had actual malignant transformation (MT) of adenomas. GSD status was similar for the 2 groups, except for age and the presence of HCC on explants (P = 0.030). Three patients with HCC on explant developed recurrence after transplantation. We obtained and studied the pathomolecular characteristics for 23 patients. In conclusion, LT should remain an extremely rare treatment for adenomatosis. Indications for transplantation primarily concern the MT of adenomas. The decision should rely on morphological data and histological evidence of MT. Additional indications should be discussed on a case‐by‐case basis. In this report, we propose a simplified approach to this decision‐making process.

Outcome after laparoscopic and open resections of posterosuperior segments of the liver

Laparoscopic resection of posterosuperior (PS) segments of the liver is hindered by limited visualization and curvilinear resection planes. The aim of this study was to compare outcomes after open and laparoscopic liver resections of PS segments.

Biliverdin Protects against Liver Ischemia Reperfusion Injury in Swine

Ischemia reperfusion injury (IRI) in organ transplantation remains a serious and unsolved problem. Organs that undergo significant damage during IRI, function less well immediately after reperfusion and tend to have more problems at later times when rejection can occur. Biliverdin has emerged as an agent that potently suppress IRI in rodent models. Since the use of biliverdin is being developed as a potential therapeutic modality for humans, we tested the efficacy for its effects on IRI of the liver in swine, an accepted and relevant pre-clinical animal model. Administration of biliverdin resulted in rapid appearance of bilirubin in the serum and significantly suppressed IRI-induced liver dysfunction as measured by multiple parameters including urea and ammonia clearance, neutrophil infiltration and tissue histopathology including hepatocyte cell death. Taken together, our findings, in a large animal model, provide strong support for the continued evaluation of biliverdin as a potential therapeutic in the clinical setting of transplantation of the liver and perhaps other organs.

Development and validation of a questionnaire evaluating the impact of hepatitis B immune globulin prophylaxis on the quality of life of liver transplant recipients.

To date, there is still a lack of instruments for specifically assessing the impact of anti–hepatitis B virus prophylaxis after liver transplantation (LT) on health‐related quality of life (HRQOL) and treatment satisfaction. Focusing on the use of hepatitis B immune globulin (HBIG), we developed and validated the Immunoglobulin Therapy After Liver Transplantation Questionnaire (ITaLi‐Q), which includes 41 items and covers 5 domains (side effects, positive and negative feelings, impact on the flexibility of daily activities, support, and satisfaction). The questionnaire was tested by 177 consecutive LT patients [71.8% were male, 38.4% were more than 60 years old, 58.8% were on intramuscular (IM) HBIG, and 41.2% were on intravenous (IV) HBIG]. A factor analysis confirmed the hypothesized structure, and a multitrait, multi‐item analysis showed favorable psychometric characteristics for ITaLi‐Q: item‐scale correlations > 0.40 for all items but 1, high scaling success rates (>90% for all scales but 1), excellent internal consistency (Cronbachs α ≥ 0.8 for all scales), and good reproducibility (test‐retest coefficient > 0.70 for all scales but 2). ITaLi‐Q was able to discriminate between subgroups of patients according to their clinical and sociodemographic characteristics. In comparison with patients on IV HBIG, patients on IM HBIG reported significantly better HRQOL scores on the Flexibility (81.5 ± 21.4 versus 73.1 ± 24.2, P = 0.01) and Negative Feelings scales (90.1 ± 17.3 versus 85.4 ± 20.7, P = 0.04), but they reported worse HRQOL scores on the Side Effects scale (81.8 ± 22.8 versus 95.6 ± 7.4, P < 0.001). No differences were found between the route of HBIG administration and the Satisfaction, Positive Feelings, Impact, and Support scales. In conclusion, ITaLi‐Q showed adequate psychometric characteristics and revealed that the route of HBIG administration has a significant impact on specific HRQOL domains beyond a patients satisfaction. Liver Transpl 18:332–339, 2012.

Simultaneous Parenchyma-Preserving Liver Resection, Cytoreductive Surgery and Intraperitoneal Chemotherapy for Stage IV Colorectal Cancer.

Background : The outcome of stage IV colorectal cancer (CRC) has improved with modern systemic therapy. However, the concomitant presence of liver metastases (LM) and peritoneal carcinomatosis (PC) remains associated with a dismal prognosis and surgery in this context remains exceptional. Methods : Stage IV CRC patients with LM and PC undergoing simultaneous cytoreductive surgery, intraperitoneal chemotherapy (IPC) and liver resection/ablation were identified from prospectively collected databases. We assessed response to neoadjuvant chemotherapy (NACT), postoperative complications, progression free survival (PFS), and overall survival (OS). Results : Twenty-one patients with resectable disease were treated between 2007 and 2014. In 16 patients (76%), NACT was administered and tumour response defined their selection. The remaining 5 (24%) were selected according to the pattern of recurrence. Median peritoneal cancer index was 5 (range : 3-10.5). Liver surgery included 34 wedge resections, 5 ablations and one bisectionectomy to treat a total of 45 hepatic lesions with a median of 2 per patient (range : 1-2) and a median size of 1.35 cm (range : 0.8-2). Tumour regression grade 4 (fibrosis but residual cancer cells predominate) was seen in 50% of the resected metastases after NACT. Median hospital stay was 17 days (range : 14-24); severe morbidity (Clavien-Dindo grade 3-4) occurred in 24% and no perioperative mortality (0-90 days) was recorded. The median OS was 44 months (range : 31-57) while the median PFS was 10 months (range : 8-12). Conclusion : Combined parenchyma-preserving liver resection, cytoreductive surgery and IPC in patients with LM and PC from CRC can be performed safely and results in promising mid-term overall survival.