D. Bassi

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.

Second hepatic resection for recurrent hepatocellular cancer: a Western experience.

BACKGROUND & AIMS Recurrence of hepatocellular cancer after resection is a significant problem. The optimal treatment of patients with intrahepatic recurrence after resection and well-preserved liver function is not clear. We analyzed the outcomes of patients undergoing a second hepatic resection for recurrent hepatocellular cancer at a single Western center. METHODS The records of all patients undergoing primary hepatic resection for hepatocellular cancer between January 1994 and January 2009 were reviewed. Patients with a single intrahepatic recurrence, Childs A liver function, and platelet count>100,000/μl underwent a second hepatic resection. Clinical data was recorded and analyzed. RESULTS Of the 487 patients undergoing primary resection, 221 developed recurrence, and 35 underwent a second hepatic resection. There were no perioperative mortalities. There were 10 deaths during the study period; 5-year overall survival was 67% from second resection. Time to recurrence from primary resection<1 year and gross vascular invasion at second resection were predictors of survival and recurrence. Patients with recurrence>1 year from primary resection and without gross vascular invasion had a 5-year survival of 81%. There were 17 recurrences with a 3-year recurrence rate of 55%. CONCLUSIONS Second hepatic resection for recurrent hepatocellular cancer is applicable in about 15% of patient with recurrence. The procedure is safe and can achieve excellent results in well-selected patients. Recurrence continues to be a significant problem.

Use of N‐acetylcysteine during liver procurement: A prospective randomized controlled study

Antioxidant agents have the potential to reduce ischemia/reperfusion damage to organs for liver transplantation (LT). In this prospective, randomized study, we tested the impact of an infusion of N‐acetylcysteine (NAC) during liver procurement on post‐LT outcomes. Between December 2006 and July 2009, 140 grafts were transplanted into adult candidates with chronic liver disease who were listed for first LT, and according to a sequential, closed‐envelope, single‐blinded procedure, these patients were randomly assigned in a 1/1 ratio to an NAC protocol (69 patients) or to the standard protocol without NAC [71 patients (the control group)]. The NAC protocol included a systemic NAC infusion (30 mg/kg) 1 hour before the beginning of liver procurement and a locoregional NAC infusion (300 mg through the portal vein) just before cross‐clamping. The primary endpoint was graft survival. The graft survival rates at 3 and 12 months were 93% and 90%, respectively, in the NAC group and 82% and 70%, respectively, in the control group (P = 0.02). An adjusted Cox analysis showed a significant NAC effect on graft survival at both 3 months [hazard ratio = 1.65, 95% confidence interval (CI) = 1.01‐2.93, P = 0.04] and 12 months (hazard ratio = 1.73, 95% CI = 1.14‐2.76, P ≤ 0.01). The incidence of postoperative complications was lower in the NAC group (23%) versus the control group (51%, P < 0.01). In the subgroup of 61 patients (44%) receiving suboptimal grafts (donor risk index > 1.8), the incidence of primary dysfunction of the liver was lower (P = 0.09) for the NAC group (15%) versus the control group (32%). In conclusion, the NAC harvesting protocol significantly improves graft survival. The effect of NAC on early graft function and survival seems higher when suboptimal grafts are used. Liver Transpl 19:135–144, 2013.

Subnormothermic Machine Perfusion for Non–Heart-Beating Donor Liver Grafts Preservation in a Swine Model: A New Strategy to Increase the Donor Pool?

We previously reported that subnormothermic machine perfusion (sMP; 20°C) is able to improve the preservation of livers obtained from non-heart-beating donors (NHBDs) in rats. We have compared sMP and standard cold storage (CS) to preserve pig livers after 60 minutes of cardiac arrest. In the sMP group livers were perfused for 6 hours with Celsior at 20°C. In the CS group they were stored in Celsior at 4°C for 6 hours as usual. To simulate liver transplantation, both sMP- and CS-preserved livers were reperfused using a mechanical continuous perfusion system with autologus blood for 2 hours at 37°C. At 120 min after reperfusion aspartate aminotransferase levels in sMP versus CS were 499 ± 198 versus 7648 ± 2806 U/L (P < .01); lactate dehydrogenase 1685 ± 418 versus 12998 ± 3039 U/L (P < .01); and lactic acid 4.78 ± 3.02 versus 10.46 ± 1.79 mmol/L (P < .01) respectively. The sMP group showed better histopathologic results with significantly less hepatic damage. This study confirmed that sMP was able to resuscitate liver grafts from large NHBD animals.

Intestinal Surgery for Crohn’s Disease: Predictors of Recovery, Quality of Life, and Costs

IntroductionThe aim of this prospective study was to analyze the impact of different surgical techniques on patients undergoing intestinal surgery for Crohn’s disease (CD) in terms of recovery, quality of life, and direct and indirect costs.Patients and methodsForty-seven consecutive patients admitted for intestinal surgery for CD were enrolled in this prospective study. Surgical procedures were evaluated as possible predictors of outcome in terms of disability status (Barthel’s Index), quality of life (Cleveland Global Quality of Life score), body image, disease activity (Harvey–Bradshaw Activity Index), and costs (calculated in 2008 Euros). Univariate and multivariate analyses were performed.ResultsSignificant predictors of a long postoperative hospital stay were the creation of a stoma, postoperative complications, disability status on the third post-operative day, and surgical access (R2 = 0.59, p < 0.01). Barthel’s index at discharge was independently predicted by laparoscopic-assisted approach, ileal CD, and colonic CD (R2 = 0.53, p < 0.01). The disability status at admission showed to be an independent predictor of quality of life score at follow-up. The overall cost for intestinal surgery for CD was 12,037 (10,117–15,795) euro per patient and stoma creation revealed to be its only predictor (p = 0.006).ConclusionsLaparoscopy was associated with a shorter postoperative length of stay; stoma creation was associated with a long and expensive postoperative hospital stay, and stricturoplasty was associated with a slower recovery of bowel function.

A New Liver Autotransplantation Technique Using Subnormothermic Machine Perfusion for Organ Preservation in a Porcine Model

BACKGROUND Hepatic resection is the gold standard of therapy for primary and secondary liver tumors, but few patients are eligible for this procedure because of the extent of their neoplasms. Improvements in surgical experience of liver transplantation (OLT), hepatic resection and preservation with sub-normothermic machine perfusion (MP) have prompted the development of a new model of large animal autotransplantation. METHODS Landrace pigs were used in this experiment. After intubation, hepatectomy was performed according to the classic technique. The intrahepatic caval vein was replaced with a homologous tract of porcine thoracic aorta. The liver was perfused with hypothermic Celsior solution followed by MP at 20 °C with oxygenated Krebs solution. An hepatectomy was performed during the period of preservation, which lasted 120 minutes, then the liver was reimplanted into the same animal in a 90° counterclockwise rotated position. The anastomoses were performed in the classic sequence. Samples of intravascular fluid, blood and liver biopsies were obtained at the end of the period of preservation in MP and again at 1 and 3 hours after liver reperfusion to evaluate graft function and microscopic damage. RESULTS All animals survived the procedure. The peak of aspartate aminotransferase was recorded 60 minutes after reperfusion and the peak of alanine aminotransferase and lactate dehydrogenase after 180 minutes. Histopathologic examination under the light microscope identified no necrosis or congestion. Intraoperative echo-color Doppler documented good patency of the anastomosis and normal venous drainage. CONCLUSION This system made it possible to perform hepatic resections and vascular reconstructions ex situ while preserving the organ with mechanical perfusion (ex vivo, ex situ surgery). Improving surgical techniques regarding autotransplantation and our understanding of ischemia-reperfusion damage may enable the development of interesting scenarios for aggressive surgical treatment or radiochemotherapy options to treat primary and secondary liver tumors unsuitable for conventional in situ surgery.

Prognostic Evaluation of the Donor Risk Index Among a Prospective Cohort of Italian Patients Undergoing Liver Transplantation

BACKGROUND/AIM The definition of an extended criteria donor for orthotopic liver transplantation (OLT) remains controversial. The donor risk index (DRI) has become the main tool to define the marginality of hepatic grafts in the United States. The aim of this study was to prospectively evaluate the prognostic ability of DRI among a cohort of Italian patients undergoing OLT. METHODS From December 2006 to March 2008, we prospectively calculated DRI in all consecutive cadaveric grafts. Recipient inclusion criteria were: adult patients with chronic liver disease enlisted for primary OLT. The primary end point was the incidence of primary graft dysfunction (PDF), namely, aspartate aminotransferase (AST) >2000 U/mL and prothrombin time <40% on postoperative days 2-7. RESULTS We enrolled 74 donor-recipient pairs fulfilling the inclusion criteria. Donor characteristics included DRI 1.7 (range, 0.9-3.0); age 57 years (range, 18-81); ultrasound signs of steatosis in 22 donors (30%); and ischemia time was 536 minutes (range, 290-690). Recipient characteristics are: age 55 years (range, 27-68); hepatocellular carcinoma in 36 subjects (49%); MELD was 16 (range, 7-39); and Child-Pugh score was 8 (range, 6-14). In terms of the primary end points, the DRI did not provide a significant PDF predictor (P = .84). Among all evaluated donor and recipient variables, the following were related to the incidence of graft PDF: donor age (P = .07), ultrasound signs of steatosis (P = .02), donor AST (P = .05), cell saver infusion (P = .07), and warm (P = .04) and cold ischemia (P = .07) times. CONCLUSION The preliminary data of this study showed a poor correlation between DRI and PDF incidence after OLT.

Liver Autotransplantation for the Treatment of Unresectable Hepatic Metastasis: An Uncommon Indication—A Case Report

Ex situ ex vivo liver surgery represents a method to expand the surgical indications to treat otherwise unresectable liver tumors. We report the case of a 38-year old woman with hepatic metastasis from a pancreatoblastoma that was judged to be unresectable due to the involvement of the three hepatic veins. To treat the primary tumor, she underwent a pancreaticoduodenectomy, adjuvant chemotherapy, and thermal ablation of a liver metastasis. After appropriate preoperative study and with the permission of the ethics committee, she underwent ex situ ex vivo liver resection. The hepatectomy was performed by removing the whole liver en bloc with the retrohepatic vena cava. The inferior vena cava was reconstructed by interposition of a prosthetic graft. The ex situ ex vivo hepatic resection, a left hepatic lobectomy included the lesion in segments 1-5-7-8. The two hepatic veins were reconstructed using patches of saphenous vein. The organ was preserved continuously for 6 hours using hypothermic perfusion with 4°C Celsior solution. The liver was then reimplanted performing an anastomosis between the reconstructed hepatic veins and the caval prostheses. The patient was discharged at postoperative day 22 and is currently disease-free at 8 months after surgery and 44 months after the initial diagnosis. Ex situ, ex vivo liver surgery offers an additional option for patients with both primary and secondary liver tumors considered to be unresectable using traditional surgical approaches.

Inflammatory fibroid polyp causing intestinal obstruction following restorative proctocolectomy for ulcerative colitis.

the abdomen ( fig. 1 ) demonstrated some fluid levels with evidence of a mass (arrow) in the pelvic region. A CT scan of the abdomen ( fig. 2 ) showed a 4-cm roundish mass occupying three-quarters of the intestinal loop proximal to the ileal pouch (arrow). An enteroscopy confirmed the presence of a polypoid sessile lesion with mucosal edema and hyperemia. A 44-year-old woman was admitted to our department for intestinal obstruction. Two years earlier the patient had undergone laparoscopic restorative proctocolectomy for steroid-resistant ulcerative colitis with a normal follow-up. At admission she presented with a 3day history of vomiting, cramping abdominal pain and rectal bleeding. The plain supine and erect radiograph of Published online: July 8, 2009

Survival benefit of transplantation for recurrence of hepatocellular carcinoma after liver resection.

BACKGROUND Liver transplantation (LT) for hepatocellular carcinoma (HCC) can be used for tumor recurrence after liver resection (LR) both for initially transplant-eligible patients as conventional salvage therapy (ST) and for non-transplant-eligible patients (beyond Milan criteria) with a goal of downstaging (DW). The aim of this study was to compare the intention-to-treat (ITT) survival rates of patients who are listed for LT, according to these two strategies. METHODS We analyzed a prospective database of 399 consecutive patients who underwent hepatic resection for HCC from 2002 to 2011 to identify patients included in the waiting list for tumor recurrence. Intention-to-treat (ITT) survivals were compared with those of patients resected for HCC within and beyond Milan criteria in the same period and not included in the LT waiting list. RESULTS The study group consisted of 42 patients, 28 in the ST group (within Milan) and 14 in the DW group (beyond Milan). The 5-year ITT survival rate was similar between the 2 groups, being 64% for ST and 60% for DW (P=.84). Twenty-five patients (15 ST and 10 DW) underwent LT, 13 (10 ST and 3 DW) were still awaiting LT, 4 (3 ST and 1 DW) dropped out of the waiting list because of tumor progression, and 7 (5 ST [33%] and 2 DW [20%]) had tumor recurrence. The 5-year ITT survival of ST patients was similar to that of 252 in-Milan HCC patients resected only (P=.3), whereas 5-year ITT survival of DW patients was significantly higher (P<.01) than that of 105 beyond-Milan HCC patients resected only. CONCLUSIONS LR seems to be a safe and effective therapy both as alternative to transplantation and as downstaging strategy for intermediate-advanced HCC. The survival benefit of salvage LT, however, seems to be higher in the 2nd than in the 1st group.