Beyond the Milan criteria: what risks for patients with hepatocellular carcinoma progression before liver transplantation?

BACKGROUND: To date the selection of the best candidates for liver transplantation (LT) owing to hepatocellular carcinoma (HCC) has been mainly based on tumor morphological characteristics (nodule diameter and number), which have resulted to be independent risk factors for short long-term survival and a high rate of tumor recurrence. METHODS: The study cohort included 118 patients among the 166 with HCC transplanted at our unit from January 2000 to December 2007. Patients were classified according to response to locoregional treatments before LT: progressive Group A; complete Group B; partial Group C; stable Group D. RESULTS: The 3-year and 5-year overall survival rates were 65.5% and 48.9% for Group A versus 84.8% and 74.6% for Group BCD (P = 0.01). The 3-year and 5-year disease-free survival rates were 74% and 74% for Group A and 95.7% and 93% for Group BCD (P = 0.007). HCC progression was the only independent risk factor according to Cox regression P = 0.014--odds ratio 4.4 (1.35-14.3). CONCLUSION: After aggressive HCC treatment before LT, imaging progression while on the waiting list was a strong predictor of high HCC recurrence rate also in patients who met the Milan criteria. Lack of imaging progression can contribute toward the selection of good transplant candidates for HCC together with the Milan criteria.

Laparoscopic versus open liver surgery: a single center analysis of post-operative in-hospital and post-discharge results.

PURPOSE: Laparoscopic hepatectomy (LH) is established as a safe and feasible surgical procedure for benign and malignant liver lesions showing many benefits in terms of short-term post-operative outcomes. Nevertheless, it remains unclear if these benefits extend beyond the hospital stay. The aim of this study was to compare in-hospital and post-discharge outcomes between two groups of patients who have undergone either laparoscopic or open hepatectomy (OH). METHODS: Forty-six patients who have undergone LH from September 2008 to September 2011 were compared to 46 matched-pair control patients who have undergone OH. The two groups were compared in terms of in-hospital and 6-month outcomes. Post-discharge outcomes were analyzed in terms of the number of outpatient clinic appointments (OCAs) and readmissions (RAs). Analyses were performed excluding and including conversion cases. RESULTS: The two groups resulted in homogeneous patients' and lesions' characteristics. Patients who underwent LH showed statistically lower intra-operative blood loss, less total and major morbidity and shorter hospital stay. Regarding post-discharge outcomes, significantly less patients of LH group compared to patients of OH group required more than two post-discharge OCAs (in the intention to treat analysis, 28.3 versus 63%, respectively; P = 0.006) or RA (4.3 versus 15.2%, respectively; P = 0.008). The benefits of LH appeared to be maximized in cirrhotic patients; those represented the large part of patients readmitted after hepatectomy regardless of the type of surgical approach (77.8%). CONCLUSIONS: Advantages related to LH extend over the post-discharge period suggesting potential better patient's satisfaction and lower hospital cost.

Living donor liver transplantation for hepatocellular carcinoma: the impact of neo-adjuvant treatments on the long term results.

BACKGROUND/AIMS: LDLT may represent a valid therapeutic option allowing several advantages for patients affected by HCC and waiting for liver transplantation (LT). However, some reports show a worse long term survival and disease free survival among patients treated by LDLT for HCC than deceased donor liver transplantation (DDLT) recipients. METHODOLOGY: Among 1145 LT patients, 63 received LDLT. From January 2000 to December 2008, 179 patients underwent LT due to HCC, 30 (16.7%) received LDLT and 154 (86.0%) received DDLT. Patients were selected based on the Milan criteria. TACE, radiofrequency ablation, percutaneous alcoholization, or liver resection were applied as downstaging procedures, while on the waiting list. RESULTS: Overall 3- and 5-year survival rate was 77.3% and 68.7% vs. 82.8% and 76.7%, respectively for LDLT and DDLT recipient with not significant differences. Moreover, 3- and 5- years of recurrence free survival rate was 95.5% (LDLT) vs. 90.5% and 89.4% (DDLT) and resulted not significantly different. CONCLUSIONS: LDLT guarantees same long term results than DDLT if the selection criteria of candidates are analogues. Milan criteria remains a valid candidate selection tool to obtain optimal long term results in LDLT. An aggressive downstaging policy seems to improve the long-term results in LDLT, thus LRT may be considered useful to prevent tumor progression waiting for transplantation as well as a neoadjuvant therapy for HCC. A literature detailed meta-analysis could definitely clarify if LDLT is an independent risk factor for HCC recurrence.

Biliary complications after liver transplantation--523 consecutive cases in two centers.

BACKGROUND/AIMS: Despite various surgical techniques, biliary tract complications (BC) remain a major source of morbidity after liver transplantation (LT). METHODOLOGY: Between April 2000 and November 2008, 523 LTs in 487 recipients (36 re transplantations) were performed as follows: 402 whole deceased donor graft LTs, and 121 partial liver transplantation: 75 living donor liver transplantation, 42 split liver transplantation, and 4 reduced size liver transplantation. RESULTS: Mean follow-up period was 935 days (range 1-3174), 1, 3 and 5-year survival rates were 78.7% 74.2% and 74.2%, respectively. One hundred twenty seven patients--from 487 (26%), developed (after 135 LT) 150 singular BC (in total were 181 BC). Sixty four (of 85) bile leaks (75.29%) were early BC, while 53 (of 63) stenosis (84.1%) were late BC. BC does not influenced significantly patients and graft survival (p > 0.6). From 102 deaths, 8 were due to BC (1.6%) and in only 14 (2.67%) graft loss of 523 LT BC had the main role. Multiple ducts, multiple biliary anastomosis and RYHJ determine BC if compared to a single duct graft. Moreover, ductoplasty, graft type and HAT were independent risk factors. CONCLUSION: Biliary complications are common after LT but are rarely an isolated cause of death.

Surgical Management of Hepatic Benign Disease: Have the Number of Liver Resections Increased in the Era of Minimally Invasive Approach? Analysis from the I Go MILS (Italian Group of Minimally Invasive Liver Surgery) Registry.

BACKGROUND: Increased expertise with minimally invasive liver surgery (MILS) could cause an unjustified extension of indications to resect liver benign disease (BD). The aim of this study was to evaluate the operative risk of MILS for BD and if implementation and diffusion of MILS have widened indications for BD resection. METHODS: A prospective study including centers with > 6 MILS for BD, enrolled in the I Go MILS registry from January 2015 to October 2016. Cysts fenestrations were excluded. RESULTS: Eight hundred eighteen MILS were performed in 15 centers. One hundred seventy-three of these (21.1%) were for BD: conversion rate was 6.9%, postoperative mortality and morbidity rates were 0 and 13.9%. During the same period, 3713 liver resections (open + MILS) were performed and 407 (11.0%) were for BD. A time-trend analysis showed that the total number of MILS and the number of MILS for malignant disease significantly increased, but this increasing trend was not documented for the number of MILS for BD, which remained stable during the study period of time. This trend was confirmed for the overall rate of resected BD (open + MILS) that remained stable. DISCUSSION: BD represents a valid indication for MILS. For BD, 21.1% of MILS was performed, rate significantly lower than that previously reported in Italy. Although an evident growth of the use of MILS was observed during the time period analysis in Italy, this trend did not correspond to an increased number of MILS for BD, and the overall rate of resected BD was comparable to that reported in previous large open series.

Should we still offer split-liver transplantation for two adult recipients? A retrospective study of our experience.

The role of split-liver transplantation (SLT) for two adult recipients is still a matter of debate, and no agreement exists on indications, surgical techniques, and results. The aim of this study was to retrospectively analyze the outcome of our series of SLT. From May 1999 to December 2006, 16 patients underwent SLT at our unit. We used 9 full right grafts (segments 5-8) and 7 full left grafts (segments 1-4). The splitting procedure was always carried out in situ with a fully perfused liver. Postoperative complications were recorded in 8 (50%) patients: 5 (55%) in full right grafts and 3 (43%) in full left grafts. No one was retransplanted. After a median follow-up of 55.82 months (range, 0.4-91.2), 5 (31%) patients died, and the 1-, 3-, and 5-year overall survival rate for patients and grafts was 69%. We considered as a control group for the global outcome 232 whole liver transplantations performed at our unit in the same period of time. Postoperative complications were recorded in 53 (23%) patients, and after a median follow-up of 57.37 months (mean, 55.11; range, 1-102.83), the 1-, 3-, and 5-year overall patient survival was 87%, 82%, and 80%, respectively. In conclusion, SLT for two adult recipients is a technically demanding procedure that requires complex logistics and surgical teams experienced in both liver resection and transplantation. Although the reported rate of survival might be adequate for such a procedure, more efforts have to be made to improve the short-term outcome, which is inadequate in our opinion. The true feasibility of SLT for two adults has to be considered as still under investigation.

Life-saving super-urgent liver transplantation with replacement of retrohepatic vena cava by dacron graft.

We describe a modified technique of side-to-side cavo-cavostomy by Dacron interposition prosthesis during a super urgent liver transplantation. A liver graft from a deceased donor was immediately requested on a top priority basis as a consequence of massive bleeding during extended left hepatectomy for a huge hepatic haemangioma arising from the caudate lobe. Veno-venous bypass was employed during anhepatic phase but it was disconnected due to severe fibrinolysis and hypothermia. A porto-caval shunt was performed and the inferior vena cava outflow was restored by a Dacron interposition prosthesis. A liver graft from a deceased donor was available 16 hours later. Due to the shortness of the vena cava of the donor liver graft, the removal of the Dacron graft was impossible and a modified side-to-side cavo-cavostomy between the Dacron interposition graft and the vena cava of the donor liver was than performed. Liver transplantation was uneventful and the patient is doing well 25 months after the surgical procedure. Although the use of synthetic vascular prosthesis should usually be discouraged during organ transplantation, its exceptional use during liver transplantation is possible with long-term good results.

Percutaneous Transhepatic Bile Duct Ablation with n-Butyl Cyanoacrylate in the Treatment of a Biliary Complication after Split Liver Transplantation.

Biliary complications continue to be a major cause of morbidity after split-liver transplantation (SLT). In this report we describe an uncommon late biliary complication. One year after SLT the patient showed an intrahepatic bile dicy dilatation with severe cholangitis episodes. The segmentary bile duct of hepatic segment VI-VII draining in the left duct was unidentified and tied at the time of the in situ split-liver procedure. We perform a permanent obliteration of the dilated intrahepatic ducts by a percutaneous embolization using an n-butyl cyanoacrylate (NABC). The management of biliary complications after SLT requires a multidisciplinary approach. The use of NBCA in obliteration of a dilated bile duct seems to be a safe procedure with good results providing a less invasive option than hepatic resection and decreasing the morbidity associated with chronic external biliary drainage. Further studies are needed to determine whether this approach is effective and safe and whether it could reduce hospital stay and cost.

Biliary complications after living donor adult liver transplantation.

The highest rate of complications characterizing the adult living donor liver transplantation (ALDLT) are due to biliary problems with a reported negative incidence of 22-64%. We performed 23 ALDLT grafting segments V-VIII without the middle hepatic vein from March 2001 to September 2005. Biliary anatomy was investigated using intraoperative cholangiography alone in the first five cases and magnetic resonance cholangiography in the remaining 18 cases. In 13 cases we found a single right biliary duct (56.5%) and in 10 we found multiple biliary ducts (43.7%). We performed single biliary anastomosis in 17 cases (73.91%) and double anastomosis in the remaining six (26%) cases. With a mean follow up of 644 days (8-1598 days), patient and graft survivals are 86.95% and 78.26%, respectively. The following biliary complications were observed: biliary leak from the cutting surface: three, anastomotic leak: two, late anastomotic strictures: five, early kinking of the choledochus: one. These 11 biliary complications (47.82%) occurred in eight patients (34.78%). Three of these patients developed two consecutive and different biliary complications. Biliary complications affected our series of ALDLT with a high percentage, but none of the grafts transplanted was lost because of biliary problems. Multiple biliary reconstructions are strongly related with a high risk of complication.

Predictors of long-term survival after liver transplantation for hepatocellular carcinoma.

AIMS: The aim of this study was to identify predictors of both survival and tumor-free survival of a cohort of 155 patients, with hepatocellular carcinoma (HCC) and cirrhosis, who were treated by orthotopic liver transplantation (OLT). METHODS: From January 1989 to December 2002, 603 OLTs were performed in 549 patients. HCC was diagnosed in 116 patients before OLT and in 39 at histological examination of the explanted livers. Eighty-four percent of the patients met "Milan" criteria at histology. Ninety-four patients received anticancer therapies preoperatively. RESULTS: The median follow-up was 49 months (range, 0-178). Overall, 1-, 3-, 5-, and 10-yr survival were 84%, 75%, 72%, and 62%, respectively. Survival was not affected by the patient's age or sex, etiology of liver disease, Child score at transplantation, rejection episodes, tumor number, total tumor burden, bilobar tumor, and pathologic Tumor, Nodes, Metastasis (pTNM) stages. There was no statistically significant difference in survival when patients were grouped according to the recently proposed simplified pTNM staging (5-yr survival, 80% in stage I, 69% in stage II, 50% in stage III, p= 0.3) or the United Network for Organ Sharing (UNOS) staging system for HCC. Encapsulation of the tumor and alpha-fetoprotein levels significantly affect patient survival. Five-year survival of patients with poorly differentiated (G3) HCC was significantly worse than that of patients with moderately (G2) or well-differentiated (G1) HCC (respectively, G3 44%, G2 67%, and G1 97%, p= 0.0015). Patients with micro- or macro-vascular invasion had a worse 5-yr survival than patients without vascular invasion (49%vs 77%, p= 0.04). Multivariate analysis showed that histological grade of differentiation and macroscopic vascular invasion are independent predictors of survival (HR 2.4, 95% CI 1.4-4.1, p= 0.0009 and HR 2.8, 95% CI 1.2-6.8, p= 0.022). CONCLUSION: Histological grade of differentiation and macroscopic vascular invasion, as assessed on the explanted livers, are strong predictors of both survival and tumor recurrence in patients with cirrhosis who received transplants for HCC.

Liver transplantation for hepatocellular cancer: should the current indication criteria be changed?

Liver transplantation (LTx) is the best treatment for hepatocellular carcinoma (HCC), but should be offered only to selected patients. The usual procedure is to transplant only for small and unilobular tumors. The aim of this paper is to verify whether the actual indication criteria are still justified. The details of 121 patients with HCC who were submitted to LTx from 1985 to 2000 were analyzed. Age, gender, liver disease, Child class, alpha-fetoprotein (AFP) level, presence of tumor capsule, vascular invasion, size and number of nodules, histological grade, and pTNM were considered. The 5- and 10-year actuarial survival rates were 61.7% and 53.1%. Freedom from recurrence was 85.9% and 85.9%, respectively. At univariate analysis, size, presence of capsule, AFP levels, vascular invasion, grade, pTNM, transarterial chemoembolization (TACE), Child class, and age were all significantly related to survival and/or cancer recurrence. Presence of capsule, AFP levels, and viral cirrhosis were independent variables in Cox's analysis for survival, whereas histological grade, AFP levels, and vascular invasion were significant independent variables for recurrence. In conclusion, a strict selection should be made to optimize graft allocation while size and multifocality should probably no longer be considered a contraindication for LTx. Histological grade, AFP levels, and vascular invasion, as indicator of tumor behavior, more likely reflect the risk of recurrence.