Prospective validation of a new priority allocation model for liver transplant candidates: an interim analysis.

BACKGROUND: The system that controls the waiting list (WL) and organ allocation for liver transplantation (OLT) seeks to achieve 3 main goals: objectivity, low dropout risks and good post-OLT results. We sought to prospectively validate a priority allocation model that is believed to achieve objectivity without penalizing dropout risk and post-OLT results. METHODS: We evaluated a study group of 272 patients enrolled in 2006-2007. WL candidates were divided into 2 categories: cirrhotic patients classified according to Model for End-Stage Liver Disease (MELD) score (MELD list and patients with hepatocellular carcinoma (HCC) organized according to a specific score (non-MELD list). The allocation algorithm for donor-recipient match assigned an optimal graft to the first MELD candidate with a MELD score of >or=20; a suboptimal graft, to the first non-MELD patient. A respective control group of 327 patients transplanted from 2003-2006 was characterized by a unique WL with a free allocation policy. We performed an interim analysis of this prospectively controlled study. RESULTS: Although the study group showed a lower percentage of OLT (P < .05) than the control group (37% vs 45%), it selected patients for OLT based on a higher MELD score (P < .05), thus obtaining similar dropout, post-OLT survivals, and intention-to-treat (ITT) survival probabilities as the controls. Among MELD patients, we observed a significantly reduced dropout and better ITT survival profiles than those of the control group (P = .02), whereas the similar results were delivered among non-MELD patients (P > .05). Among patients with a MELD score of >or=20, the prevalences of suboptimal grafts (0% vs 48%) and of early graft losses (0% vs 21%) were lower in the study than in the control group (P < .05). CONCLUSIONS: We prospectively validated a priority allocation model based on objective criteria that achieved high ITT survival rates.

Validation of the BCLC prognostic system in surgical hepatocellular cancer patients.

BACKGROUND/AIM: Prognosis assessment in surgical patients with hepatocellular carcinoma (HCC) remains controversial. The most widely used HCC prognostic tool is the Barcelona Clinic Liver Cancer (BCLC) classification, but its prognostic ability in surgical patients has not been yet validated. The aim of this study was to investigate the value of known prognostic systems in 400 Italian HCC patients treated with radical surgical therapies. METHODS: We analyzed a prospective database collection (400 surgical, 315 nonsurgical patients) observed at a single institution from 2000 and 2007. By using survival times as the only outcome measure (Kaplan-Meier method and Cox regression), the performance of the BCLC classification was compared with that of Okuda, Cancer of the Liver Italian Program, United Network for Organ sharing TNM, and Japan Integrated Staging Score staging systems. RESULTS: Two hundred twenty-five patients underwent laparotomy resection; 55, laparoscopic procedures (ablation and/or resection); and 120, liver transplantations. In the surgical group, BCLC proved the best HCC prognostic system. Three-year survival rates of patients in BCLC Stages A, B, and C were 81%, 56%, and 44% respectively, (P < .01); whereas all other tested staging systems did not show significant stratification ability. When all 715 HCC patients were considered, surgery proved to be a significant survival predictor in each BCLC stage (A, B, and C). CONCLUSIONS: BCLC staging showed the best interpretation of the survival distribution in a surgical HCC population. The BCLC treatment algorithm should consider the role of surgery also for intermediate-advanced stages of liver disease.

Gastrointestinal telangiectasia: a study by EGD, colonoscopy, and capsule endoscopy in 75 patients.

BACKGROUND: The distribution of lesions in the gastrointestinal tract in patients with sporadic telangiectasia is at present unknown. PATIENTS AND METHODS: 75 patients with sporadic telangiectasia underwent esophagogastroduodenoscopy (EGD), capsule endoscopy, and colonoscopy. Endoscopic diagnosis of telangiectasia and gastrointestinal bleeding were required for enrollment in the study. Hemorrhagic diathesis, co-morbidity, number of blood transfusions, and subsequent management were also noted. RESULTS: 35 of the patients presented with gastroduodenal vascular lesions, 51 with small-bowel lesions, and 28 with colonic lesions. 67 % of patients in whom EGD found telangiectasia also presented small-bowel vascular lesions at capsule endoscopy and 43 % colonic lesions at colonoscopy. 54 % percent of patients with positive colonoscopy also presented gastroduodenal lesions and 48 % small-bowel lesions. Patients with known duodenal lesions were more likely to have small-bowel lesions at capsule endoscopy (odds ratio [OR] 10.19, 95 % CI 2.1 - 49.33, P = 0.003). Patients with associated diseases, such as liver cirrhosis, chronic renal failure, or heart valvulopathy, presented more severe disease requiring blood transfusions (OR 6.37, 95 % CI 1.39 - 29.2, P = 0.015). The number of blood transfusions correlated with the number of sites affected ( R = 0.35, P = 0.002). The detection of new lesions at capsule endoscopy allowed new treatment in 46 % of patients. Mean follow-up was 18 months. CONCLUSIONS: Sporadic telangiectasia is a multifocal disease potentially involving the whole digestive tract. Patients with duodenal telangiectasia show a higher risk of jejunal or ileal lesions. Capsule endoscopy is a useful diagnostic tool for the detection of such small-bowel vascular lesions, indicating a more specific prognosis and treatment strategy.

Long-term results of liver transplantation for hepatocellular carcinoma: an update of the University of Padova experience.

BACKGROUND: Hepatocellular carcinoma (HCC) competes with benign liver disease as indication for liver transplantation (OLT). The aim of this study was to determine long-term results of OLT for HCC. METHODS: We retrospectively analyzed the prognostic role of HCC diagnosis at pathological exam in adult OLT. In the HCC group, we evaluated the prognostic role of the time of diagnosis (incidental versus nonincidental) and of pathological tumor TNM staging. The primary endpoint was 1-, 3-, and 10-year patient survivals. RESULTS: From 1991 to 2006, among 550 adults who underwent first OLT, HCC was found in 120 patients at pathological exam. In 26 cases (22%), the diagnosis of HCC was incidental. There were 59 cases (49%) of pathological T1 to T2 tumor (one nodule < 5 cm, or two to three nodules < 3 cm, without metastases and/or vascular invasion), and 61 cases (51%) of pathologic T3-T4a tumor. HCC diagnosis did not show a significant prognostic impact by Cox survival analysis. After a median follow-up of 31 months, 1-, 5-, and 10-year survivals were 91%, 81%, and 73% in the HCC group, and 84%, 76%, and 67% in the non-HCC group. Time of HCC diagnosis (incidental versus nonincidental) and pathological TNM staging (T1 to T2 vs T3 to T4a) did not result significant survival predictors upon Cox analysis. CONCLUSION: In our experience, the long-term results of OLT for HCC overlapped those of OLT for benign disease, although 51% of tumors were T3 to T4a at pathological exam.

Hepatitis C virus-related cirrhosis as a significant mortality factor in intention-to-treat analysis in liver transplantation.

INTRODUCTION: Liver transplantation represents the gold standard for the treatment of chronic liver disease. The whole transplantation process was assessed using an intention-to-treat analysis and considering patients from the time of their inclusion on the list and throughout lengthy follow-up. MATERIALS AND METHODS: From January 1, 1999 to June 1, 2004, 373 adults joined the waiting list for liver transplantation at our institution. The main variables analyzed were: age, gender, etiology, Model for End-stage Liver Disease score, Child-Pugh class, United Network for Organ Sharing (UNOS) status. Global survival was evaluated using intention-to-treat analysis from the time of patient inclusion in the list to the end of their late follow-up. RESULTS: The median waiting time was 20 months (range 0.1 to 70.2). By univariate analysis, the variables significantly influencing survival when patients joined the waiting list were: encephalopathy; ascites, poor nutritional status, Child-Pugh class C, UNOS 2, hepatitis C virus (HCV) and bilirubin > 2 mg/dL. By multivariate analysis, only HCV-related cirrhosis emerged as having an independent prognostic value. By intention-to-treat analysis, the 5-year survival rate was 67% and 79% for HCV-positive and HCV-negative patients, respectively (P = .0003). CONCLUSIONS: HCV-related cirrhosis is an independent prognostic factor for survival according to an intention-to-treat analysis. Different inclusion criteria or treatments while on the waiting list and after transplantation need to be considered in the future for HCV-positive patients.

Prognostic impact of model for end-stage liver disease score in patients undergoing liver transplantation with suboptimal livers.

BACKGROUND/AIMS: The aim of this retrospective study is to analyze the prognostic impact of Model for End-Stage Liver Disease (MELD) score in patients undergoing liver transplantation (OLT) with suboptimal livers. METHODS: Between January 2002 and January 2006, 160 adult patients with liver cirrhosis received a whole liver for primary OLT at our institution including 81 with a suboptimal liver (SOL group) versus 79 with an optimal liver (group OL). The definition of suboptimal liver was: one major criterion (age >60 years, steatosis >20%) or at least two minor criteria: sodium >155 mEq/L, Intensive Care Unit stay >7 days, dopamine >10 microg/kg/min, abnormal liver tests, and relevant hemodynamic instability. RESULTS: Baseline recipients characteristics were comparable in the two study groups. The SOL group had a significantly greater number of early graft deaths (<30 days) than the OL group, while the 3-year Kaplan-Meier patient survivals were similar. Using logistic regression, MELD score was significantly related to patient death only in the SOL group (P = .01), and the receiver operator characteristics curve method identified 17 as the best MELD cutoff with the 3-year survival of 93% versus 85% for MELD < or =7 versus >17, respectively (P > 05). In comparison, it was 94% and 72% in the SOL group (P < .05). Similarly, MELD >17 was significantly associated with early graft death rates only in the SOL group. CONCLUSION: This study advised surgeons to not use suboptimal livers for patients with advanced MELD scores, thus supporting a donor-recipient matching policy.

Combined liver and kidney transplantation: analysis of Padova experience.

BACKGROUND/AIM: The main indications for combined liver and kidney transplantation (CLKT) are as follows: (1) cirrhosis with renal damage dependent or not upon liver disease, (2) renal failure with dialysis and concomitant liver end-stage disease, (3) congenital diseases, and (4) enzymatic liver deficiency with concomitant renal failure. The aim of this study was to evaluate our results with CLKT both in adult and pediatric patients. METHODS: From September 1995 to September 2006, 15 CLKT (2.8%) among 541 liver transplantations included 4 pediatric patients (27%). The main indications for CLKT were hepatitis C virus (HCV) and polycystic diseases in adult patients, and primary hyperoxaluria in pediatric patients. RESULTS: The double transplantation was performed from the same donor in all cases. All adult patients received whole liver grafts, whereas 3 split transplants and 1 whole liver graft were transplanted in the pediatric patients. Median liver and kidney cold ischemia times were 468 and 675 minutes, respectively. After a median follow-up of 36 months (range, 1-125), the overall survival rate was 80%. Five-year patient and graft survival rates were 100% for adult CLKT, whereas they were 50% for pediatric patients. We observed only 2 cases (18%) of delayed renal function, requiring temporary hemodialysis with progressive graft improvement. There was only 1 case of kidney retransplantation due to early graft nonfunction in a pediatric patient. CONCLUSION: Although CLKT is related to major surgical risks, results after transplantation are satisfactory with an evident immunological advantage.

Pediatric liver transplantation: the University of Padua experience.

OBJECTIVE: The objective of this study was to analyze experience on pediatric liver transplantation (LT) between June 1993 and September 2006, including split liver transplantation (SLT), living donor liver transplantation (LDLT), and auxiliary partial orthotopic liver transplantation (APOLT). Furthermore, hepatocyte transplantation (HT) had a role in one patient with metabolic disease. METHODS: From November 1990 to September 2006, 657 LTs were performed including 63 pediatric LTs (9.6%) in 57 patients (32 boys and 25 girls). Six were retransplantations (9.5%). Thirty-two patients (57%) were younger than 5 years. The types of graft included the following: 26 whole organs (41%), 32 in situ split organs (51%), 4 reduced-size organs (6%), and 1 graft from a living donor (2%). Two patients received an APOLT, 4 patients received a combined kidney-liver transplantation (CKLT), and 1 patient received HT. Of the 63 pediatric LTs, 16 were behaved to be highly urgent (25%). RESULTS: Overall 1-, 3-, 5-, and 10-year patient survival rates were 82%, 82%, 78%, and 78%, respectively. Overall 1-, 3-, 5-, and 10-year graft survival rates were 76%, 76%, 72%, and 72%, respectively. In patients younger than 1 year, the 5-year survival rate was 100%. Perioperative mortality was 8.8%. Vascular complications occurred in 4 patients (6.3%). Six children required retransplantation due to primary nonfunction (PNF) in 4 cases (7%) and vascular thrombosis in 2 cases (3.5%). CONCLUSIONS: Cholestatic liver disease and age younger than 1 year were the best prognostic factors for excellent survival.

Endoscopic treatment of bile duct complications after orthotopic liver transplantation.

AIM: To assess the indications and results of endoscopic retrograde cholangio-pancreatography (ERCP) in patients who have undergone ortotopic liver transplantation (OLT). METHODS: We reviewed data from 42 consecutive patients who underwent ERCP for biliary complications after OLT over an 8-year period, in particular recording indications and success of the treatment after a mean of 17 months follow-up. RESULTS: Cholangiograms performed in 33/42 patients (79%) displayed anastomotic strictures in 17 patients (52%), bile duct stones in 8 (24%), both bile duct stones and an anastomotic stricture in 2 (6%), papillary stenosis in 1 (3%), and anastomotic biliary leakage in 1 (3%). In contrast, the contrastogram was normal in four patients (12%). Stone extraction was completed in 9/10 patients (90%) with a mean of 1.2 sessions, while stricture dilation was achieved in 12/19 patients (63%) after a mean of 1.7 sessions, by stent positioning (n = 7), balloon dilation (n = 4), or Soehendra dilator (n = 1). Both biliary leakage and papillary stenosis were cured by ERCP. Only one procedure-related complication -- severe pancreatitis (2.4%) -- was observed and no mortality. CONCLUSION: ERCP is a safe and effective mode of management of bile duct complications after OLT. It should be attempted before a surgical approach. Better results are obtained for treatment of biliary stones than of anastomotic strictures.

A new experimental model of isolated perfused pig liver to support acute hepatic failure.

Liver transplantation still represents the only effective treatment for patients with liver failure, but many patients die while awaiting transplantation, even though many attempts have been made to increase the organ procurement rates and to partially support hepatic function in recent years. Our aim was to design an "open" ex vivo perfused liver model to simplify liver support using an isolated porcine liver perfused with arterial and portal blood from the recipient pig, while monitoring the metabolic capacity of the supporting graft. It was possible to perfuse the isolated liver for 6 hours as a bridging procedure with satisfactory hemodynamic homeostasis controlled by software biofeedbacks.

Intention-to-treat analysis of liver transplantation in selected, aggressively treated HCC patients exceeding the Milan criteria.

This prospective study analyzed the dropout probability and intention-to-treat survival rates of patients with hepatocellular carcinoma (HCC) selected and treated according to our policy before liver transplantation (LT), with particular attention to those exceeding the Milan criteria. Exclusion criteria for LT were macroscopic vascular invasion, metastases, and poorly differentiated disease at percutaneous biopsy. A specific multi-modal adjuvant algorithm was used to treat HCC before LT. A total of 100 HCC patients were listed for LT: 40 exceeded the Milan criteria in terms of nodule size and number (MILAN OUT) either at listing or in list, while 60 patients continued to meet the criteria (MILAN IN). The Milan criteria did not prove to be a significant predictor of dropout probability or survival rates using Cox's analysis. Cumulative dropout probability at 6 and 12 months was 0% and 4% for MILAN OUT, and 6% and 11% for MILAN IN. The intention-to-treat survival rates at 1 and 3 years were 95% and 85% in MILAN OUT, and 84% and 69% in MILAN IN. None of the 68 transplanted patients had recurrent HCC after a median 16-month follow-up (0-69 months). In conclusion, LT may be effective for selected, aggressively-treated HCC patients exceeding the Milan criteria.

Cystadenoma and laparoscopic surgery for hepatic cystic disease: a need for laparotomy?

BACKGROUND: This study aimed to evaluate the incidence of cystadenoma diagnosis in a series of laparoscopic treatments for nonparasitic liver cysts, as well as its management. METHODS: From 1996 to 2004, 26 patients with a nonparasitic cyst of the liver were selected for laparoscopic liver surgery. Solitary nonparasitic liver cysts were, whenever feasible, completely enucleated. RESULTS: In four patients, the histopathologic examination showed a cystadenoma. Three patients with 13, 9, and 12-cm cysts, respectively, had undergone complete enucleation of the lesion, with no evidence of recurrence in the follow-up visit. One patient with multicystic liver experienced a recurrence and required an open hepatic resection. CONCLUSIONS: When a complete laparoscopic enucleation of the cyst can be ensured, a strict follow-up assessment should be considered as the definitive treatment, with surgical intervention demanded only in the case of recurrence or high suspicion for malignancy.

Laser photoablation of colorectal adenomas: a 12-year experience.

BACKGROUND: We analyze laser photoablation as an alternative treatment of large sessile polyps in inoperable patients. METHODS: Ninety-four colorectal polyps (mean diameter 3.09 +/- 2.7 cm, range 1-15 cm) were treated using high-energy lasers (Nd:YAG and diode). Grade of dysplasia was low in 51, high in 35, with focally invasive cancer in eight. RESULTS: After 405 laser sessions (4.3 per polyp) five procedure-related complications were observed: two strictures, two bleedings, and one perforation. The last needed a surgical resection; the others were successfully treated by endoscopic therapy. Fifty-seven polyps (61%) were completely eradicated and the growth was controlled in all but two (98%). No degeneration was found after 28-month follow-up of treated adenomas with low- or high-grade dysplasia. Outcome of treatment was dependent on the dimension and grade of the dysplasia (p < 0.05), but not on the polyps' position (rectum or colon). Relief of rectal bleeding was obtained in 90%, of mucus discharge in 77%, and of tenesmus in 100% of cases. CONCLUSIONS: Laser photoablation of colonic adenomas can be considered a valid procedure not only to relieve symptoms, but also to control the risk of degeneration in patients unfit for surgery or when surgical treatment is considered excessively invalidating.

The radical treatment of gastric carcinoma.

AIM: The aim of this paper is to review and assess the selective principles for a radical treatment of gastric carcinoma with respect to resection type as well as the role of lymphadenectomy. METHODS: From 1994 to 1999, we operated 222 patients affected by gastric adenocarcinoma at the 1st Surgical Clinic Institute in Padua. Out of the whole group, 138 patients (62.1%) underwent radical surgical treatment (75 patients with total gastrectomy, extended in 30 cases, and 63 patients by means of gastric resection). RESULTS: The overall survival rate at a median follow-up of 4 years was 58% for the patients treated with total gastrectomy, and 77% in case of distal gastric resection; 97% of patients with early gastric cancer are alive at a median follow-up of 3 years. CONCLUSION: Whenever it is feasible, subtotal gastrectomy could ensure a radical treatment of gastric carcinoma with low morbidity and mortality rate. The survival rate of such patients was 77%. Prognosis of early gastric cancer is excellent. Patients with IV stage tumors surgically treated had a poor outcome, and they should be susceptible of a multidisciplinary palliative approach.

An experimental swine model of small bowel cross transplantation.

AIM: In this study we evaluated the possibility of performing a cross small bowel transplantation (CrSBTx) in which, at the same time, 2 pigs were both donors and later recipients of intestinal grafts. The hemodynamic and metabolic impact of this original transplantation model on the animals was determined. METHODS: Ten large White adult female pigs underwent a 2 stage procedure. The principal intraoperative hemodynamic and metabolic parameters were measured at different times during the operation. In the 3 days that followed the operation, renal function, liver and pancreatic damage were investigated. RESULTS: Our surgical model permits us to keep excellent hemodynamic and metabolic stability with low mortality. CONCLUSION: The need of half of animals with respect to conventional models represents an ethical and economic advantage of CrSBTx and we propose it for intestinal transplant studies in large animals.

Psoas abscess: a rare complication of Crohn's disease.

UNLABELLED: Psoas abscess is a rare complication of Crohn's disease. METHODS AND MATERIALS: We evaluated the incidence of psoas abscess on 312 patients with Crohn's disease, seen at our institution between 1992-2001. RESULTS: We encountered three cases of psoas abscess (0.9%). One patient was managed with ileocolic resection and immediate anastomosis, while in two patients a percutaneous drainage was first performed and then, after 12 days of total parenteral nutrition, a resection of the diseased bowel with immediate reconstruction was carried out. CONCLUSIONS: A correction of the nutritional deficiencies is mandatory. Percutaneous computed-tomography guided drainage of the abscess with intestinal resection with immediate anastomosis, performed after a parenteral hyperalimentation, should be the method of choice in the management of such patients.

Liver transplantation for the management of hepatoblastoma.

INTRODUCTION: Hepatoblastoma (HEP) is the most frequent liver malignancy occurring in childhood. Surgical resection currently represents the gold standard for treatment. In patients with initially unresectable tumors, chemotherapy may induce remarkable reductions in size. In nonresponder patients, liver transplantation (OLTx) may offer a chance of cure. MATERIALS AND METHODS: From 1990 to 2003, a total of 400 OLTx (31 pediatric transplants) have been performed at Padua University. Seven patients (4 males and 3 females) underwent OLTx for hepatoblastoma. All patients presented with bilobar liver involvement and had received chemotherapy according to the SIOPEL-1. In all patients preoperative staging was negative for extrahepatic involvement. RESULTS: The mean age of the pts was 8.2 years (range 6.4 months to 34 years). Mean follow-up after OLTx was 41.4 months (median 36, range 3 to 108 months). Actuarial patient survival rates after OLTx for hepatoblastoma are 83.3%, 83.3%, and 56% at 1, 3, and 5 years, respectively. Five of seven subjects with HEP are alive after transplant at 3, 12, 36, 65, and 108 months. Two patients died owing to recurrent disease after 6 and 60 months, respectively, from transplantation. Another subject, primarily treated with surgical resection, shows HEP recurrence at 40 months after OLTx. The remaining 4 patients are alive and well at a mean follow-up of 28 months (median 24, range 3 to 65 months). CONCLUSIONS: Liver transplantation may represent a valid therapeutic option for patients with unresectable HEP, but it is contraindicated in cases of recurrence following previous resection surgery. Neo-adjuvant chemotherapy is of paramount importance to obtain good long-term results.

Bioartificial liver support. Review and personal experience.

End-stage liver disease is treated successfully by liver transplantation. In spite of the recent advances in transplantation techniques, donor organ shortage remains a serious problem. Conditions such as fulminant hepatic failure are still burdened by a high mortality rate. This has prompted the design of an extracorporeal liver assist device, to "bridge" patients over until they either recover or receive a liver transplant. In these devices, various types of liver cells are inserted and different device designs have been proposed. The paper will review different models of bioartificial liver and will describe ongoing clinical trials. At the end we will report our experimental experience with a newly designed bioartificial liver, evaluating its beneficial effect on acute liver failure.