Outcome after curative resection for a huge (≥10 cm) hepatocellular carcinoma and prognostic significance of gross tumor classification

Background and objectives

The purpose of this study was to investigate the surgical outcomes in patients with huge (≥10 cm) hepatocellular carcinoma (HCC).

Methods

Clinicopathological features and surgical outcomes of 50 patients with huge HCC who underwent curative resection (group A) were compared with 447 patients with smaller tumors (group B). In group A, we investigated prognostic factors.

Results

Group A patients had a higher incidence of α-fetoprotein at more than 1,000 IU/mL, microscopic vascular invasion, and advanced stage tumors. The disease-free survival of group A was significantly worse than group B. The rates of initial extrahepatic recurrence and early recurrence were higher in group A. The 5 year-overall survival of group A was 40.2%, significantly lower than that of group B (65.9% at 5 years). In group A, multivariate analysis revealed that the presence of single nodular type tumors was the only good prognostic factor for survival.

Conclusions

Huge HCCs exhibit a more aggressive clinical behavior and worse survival. However, because the outcome of surgical treatment is far better than that of nonsurgical treatment, resection should be actively considered for patients with huge HCC. A single nodular type tumor is the best candidate for surgical resection.     

Late recurrence of hepatocellular carcinoma after liver transplantation: is an active surveillance for recurrence needed?

Introduction

Liver transplantation (OLT) is considered the most efficient therapeutic option for patients with liver cirrhosis and early stage hepatocellular carcinoma (HCC) in terms of overall survival and recurrence rates, when restrictive selection criteria are applied. Nevertheless, tumor recurrence may occur in 3.5% to 21% of recipients. It usually occurs within 2 years following OLT, having a major negative impact on prognosis. The efficacy of active posttransplantation surveillance for recurrence has not been demonstrated, due to the poor prognosis of recipients with recurrences.

Aim

To analyze the clinical, pathological, and prognostic consequences of late recurrence (>5 years after OLT).

Method

We analyzed the clinical records of 165 HCC patients including 142 males of overall mean age of 58 ± 6.9 years who underwent OLT between July 1994 and August 2011.

Results

Overall survival was 84%, 76%, 66.8%, and 57% at 1, 3, 5, and 10 years, respectively. Tumor recurrence, which was observed in 18 (10.9%) recipients, was a major predictive factor for survival: its rates were 72.2%, 53.3%, 26.7%, and 10% at 1, 3, 5, and 10 years, respectively. HCC recurrence was detected in 77.8% of patients within the first 3 years after OLT. Three recipients (100% males, aged 54-60 years) showed late recurrences after 7, 9, and 10 years. In only one case were Milan criteria surpassed after the examination of explanted liver; no vascular invasion was detected in any case. Recurrence sites were peritoneal, intrahepatic, and subcutaneous abdominal wall tissue. In all cases, immunosuppression was switched from a calcineurin-inhibitor to a mammalian target of rapamycin inhibitor. We surgically resected the extrahepatic recurrences. The remaining recipient was treated with transarterial chemoembolization with doxorubicin-eluting beads and sorafenib. Prognosis after diagnosis of recurrence was poor with median a survival of 278 days (range, 114-704).

Conclusions

Global survival, recurrence rate, and pattern of recurrence were similar to previously reported data. Nevertheless, in three patients recurrence was diagnosed >5 years after OLT. Although recurrence was limited and surgically removed in two cases, disease-free survival was poor. Thus, prolonged active surveillance for HCC recurrence beyond 5 years after OLT may be not useful to provide a survival benefit for these patients.     

Effectiveness of locoregional therapy before living donor liver transplantation in patients with hepatocellular carcinoma who meet the Milan criteria

Background

Many patients are diagnosed with hepatocellular carcinoma (HCC) within the Milan criteria. In Korea, these patients are preferentially treated with locoregional therapy (LRT) instead of living donor liver transplantation. We investigated the effectiveness of LRT in liver transplant recipients who met the Milan criteria at the time of HCC diagnosis and investigated risk factors for HCC recurrence.

Methods

We retrospectively reviewed the medical records of patients diagnosed with HCC who met the Milan criteria between 2002 and 2008.

Results

We performed 101 liver transplants for HCC during the study period. Seventy-one patients (70%) underwent pretransplant LRT. The disease-free survival rates at 1, 3, and 5 years in patients who received LRT were 96.6%, 93.1%, and 93.1%, and in those who did not receive LRT, 94.2%, 83.4%, and 83.4%, respectively. There were no differences between the 2 groups. Multivariate analysis showed that a low Model for End-Stage Liver Disease (MELD) score and microvascular invasion were independent predictors of HCC recurrence after transplantation. The MELD scores and rate of microvascular invasion were not statistically different in patients with or without previous LRT.

Conclusion

Pretransplant LRT for patients with HCC who met the Milan criteria at the time of diagnosis did not provide a clear benefit with respect to HCC recurrence after transplantation. If patients have suitable living donors, those who meet the Milan criteria should undergo a liver transplantation as soon as possible.     

Sirolimus-Based Immunosuppression Therapy in Liver Transplantation for Patients With Hepatocellular Carcinoma Exceeding the Milan Criteria

Aim

Sirolimus (SRL) acts as a primary immunosuppressant or antitumor agent. The aim of the present study was to evaluate the influence of SRL on the recurrence rate and survival of patients after orthotopic liver transplantation (OLT) for hepatocellular carcinoma (HCC) exceeding the Milan criteria.

Materials and Methods

We retrospectively examined 73 consecutive patients who underwent OLT for HCC exceeding the Milan criteria from March 2004 through December 2005. Among them, 27 patients were treated with SRL-based immunosuppressive protocols after OLT, and 46 patients by an FK506-based protocol. Statistical analysis was based on the intent-to-treat method.

Results

The 2 groups were comparable in all clinicopathologic parameters. The mean overall survival was 594 ± 35 days in the SRL group and 480 ± 42 days in the FK506 group (P = .011); the mean disease-free survival period was 519 ± 43 days in the SRL group and 477 ± 48 days in the FK506 group (P = .234). Multivariate analysis revealed Child's status (P = .004) and immunosuppressive protocol (P = .015) were the significant factors affecting overall survival. Only microvascular invasion (P = .004) was significantly associated with disease-free survival. Among 24 surviving patient in the SRL group, 2 patients had SRL discontinued for toxicity; 10 had SRL monotherapy immunosuppression.

Conclusion

The SRL-based immunosuppressive protocol improved the overall survival of patients after OLT for HCC exceeding the Milan criteria, probably by postponing recurrence and with better tolerability.     

Hepatocellular Carcinoma and Liver Transplantation: A 12-Year Experience

Background

Orthotopic liver transplantation (OLT) for patients with cirrhosis and concomitant hepatocellular carcinoma (HCC) in early stages is the treatment of choice, with an acceptable recurrence rate and excellent survival.

Aim

We sought to evaluate (1) the accuracy of preoperative imaging; (2) the impact of pre-OLT treatments on survival and recurrence; and (3) the influence of beyond Milan criteria selection on global outcomes.

Methods

We studied a cohort of 65 patients with HCC among 300 consecutive OLTs over a single 12-year experience. We analyzed the overall outcomes of survival and recurrence, the accuracy of preoperative diagnosis and staging the influence of neoadjuvant treatment prior to OLT, and the effect on overall outcomes beyond the Milan criteria in our series.

Results

The 65 transplants were performed for HCC, mostly in association with hepatitis C virus and alcoholic cirrhosis with HTP. At a mean follow-up of 40.32 months, the recurrence rate was 5.7% among the 61 HCC confirmed by histopathology. The overall survival was 30.07. Actuarial survivals at 1, 5, and 10 years were 82%, 77%, and 62%, respectively. Six retransplants occurred among the seven graft losses albeit with poor survival after the second graft. Most explants showed low pTNM stages with favorable microscopic features. Preoperative imaging tests failed to achieve an accurate diagnosis in 15.38% of the series. The role of alpha-fetoprotein (AFP) and hepatic biopsy was irrelevant. Unfavorable histopathologic factors predicted a greater recurrence rate, but had no influence on survival. Neither recurrence nor survival were modified by pre-OLT therapy.

Conclusions

In our series, AFP, hepatic biopsy, and pre-OLT treatment had limited roles. Radiological imaging techniques underestimated HCC staging and lead to a misdiagnosis to an expected degree. Despite these findings, this single institution experience with OLT for HCC showed excellent survivals with a low recurrence rate including cases of patients beyond the Milan criteria.     

Treatment of Hepatocellular Carcinoma With Liver Transplantation: A Single-Center Experience From Brazil

Introduction

Orthotopic liver transplantation (OLT) is the treatment of choice of hepatocellular carcinoma (HCC) for patients with cirrhosis, mainly those with early HCC. Herein we have present the clinical characteristics and outcomes of cirrhotic patients with HCC who underwent OLT from cadaveric donors in our institution.

Methods

From May 2001 to May 2009, we performed 121 OLT including 24 patients (19.8%) with cirrhosis and HCC within the Milan criteria. In 4 cases, HCC was an incidental finding in the explants.

Results

The patients' average age was 55 ± 10 years, including 82% men. Fifty percent of patients were Child class B or C. The average Model for End Stage Liver Disease for Child A, B, and C categories were 11, 15, and 18, respectively. The HCC diagnosis was made by 2 dynamic images in 16 cases; 1 dynamic image plus alphafetoprotein >400 ng/mL in 4; and 4 by histologic confirmation. Twenty patients received a locoregional treatment before OLT: 6 percutaneous ethanol injection, 9 transarterial chemoembolization, 1 transarterial embolization, and 4 a combination of these modalities. The median follow-up after OLT was 19.7 months (range, 1-51). A vascular invasion was observed in the explant of 1 patient, who developed an HCC recurrence and succumbed at 8 months after OLT. Two further patients, without vascular invasion or satellite tumor displayed tumor recurrences at 7 and 3 months after OLT, and death at 2 and 1 month after the diagnosis. The remaining 25 patients have not shown a tumor recurrence.

Conclusion

In the present evaluation, OLT patients with early HCC and no vascular invasion showed satisfactory results and good disease-free survival. Strictly following the Milan criteria for liver transplantation in patients with HCC greatly reduces but does not completely avoid, the chances of tumor recurrence.     

Hepatocellular Carcinoma in Unrelated Viral Cirrhosis: Long-Term Results After Liver Transplantation

Introduction

Chronic viral hepatitis is considered to be the most significant risk factor for development of hepatocellular carcinoma (HCC). Nevertheless, about 5%-15% of HCC occur in noncirrhotic or virus-unrelated cirrhotic patients. The natural history of HCC in terms of incidence, clinical features, and tumor progression differs according to the underlying cancerogenic factors and differences in hepatocarcinogenetic pathways. Little is know about the relationship between HCC outcomes after liver transplantation (OLT) and the primary liver disease. We retrospectively analyzed the outcomes of patients transplanted due to HCC in settings of either virus—related or virus-unrelated cirrhosis.

Patients and Methods

From January 2000 to December 2007, 179 patients underwent OLT due to HCC: 157 (87.8%) affected by virus-related (group A) and 22 (12.2%) virus-unrelated cirrhosis (group B). We analyzed patient characteristics including demographics, tumor features, downstaging treatments, and recurrences.

Results

At a mean follow-up of 41.2 months, the 3- and 5-year overall long-term survivals between group A versus group B were 81% versus 75% and 85% versus 78.4% respectively (P = NS). The 3- and 5-year disease-free survivals between group A versus group B were 90.8% versus 89.6% and 85.6% versus 85.6%, respectively (P = NS). After OLT, HCC recurrences occurred in 14 group A (14/157, 8.9%) and 4 patients (4/22, 18.1%) group B subjects.

Discussion

Our data demonstrated that after OLT, HCC outcomes were not different between patients with virus-related or -unrelated cirrhosis. The direct oncogenetic role played by hepatitis B and C appear to not be associated with a greater risk to develop HCC recurrence.     

Extended criteria for living donor liver transplantation in patients with advanced hepatocellular carcinoma

Background

The purpose of this study was to evaluate the possibility of expanding the selection criteria in living donor liver transplantation (LDLT) to treat hepatocellular carcinoma (HCC).

Methods

From October 2000 to December 2010, we retrospectively analyzed 71 patients who had undergone LDLT beyond the Milan criteria (MC), among the entire cohort of 199 HCC patients. We evaluated the tumor biology as well as overall and disease-free survival (DFS), seeking to identify risk factors for recurrence. The median follow-up was 37 months (range 5-124).

Results

Among the 71 patients beyond the MC were 18 recurrences and 30 deaths. Their 5-year overall and DFS rates were 52.3% and 67.7%, respectively. On multivariate analysis, tumor diameter, tumor number, and E-S grade significantly influenced overall and DFS. According to our new criteria (size ≤7 cm, number ≤7), 86% of our patients would be included compared with 64% using MC. Five-year DFS and overall survival rates according to our criteria were comparable with the MC: 86.8% and 72.3% versus 86.8% and 73.4%, respectively.

Conclusion

Our criteria appear to achieve useful cut-off values beyond the MC.     

Adjuvant transcatheter arterial chemoembolization improves efficacy of hepatectomy for patients with hepatocellular carcinoma and portal vein tumor thrombus

Purpose

To study the value of postoperative transcatheter arterial chemoembolization (TACE) to improve the efficacy of hepatectomy and tumor thrombus removal for patients with hepatocellular carcinoma (HCC) and portal vein tumor thrombus (PVTT).

Experimental design

From January 1996 to December 2004, 126 patients with HCC and PVTT were randomly assigned into 2 groups: a control group and a TACE group. The control group underwent liver resection combined with PVTT removal, and the TACE group underwent liver resection combined with adjuvant TACE after surgery. Survival time in the 2 groups was studied.

Results

The 2 groups were comparable with regard to all clinicopathologic data. The median survival time was 13 months (95% confidence interval [CI] 6.25 to 19.75 months) for the TACE group and 9 months (95% CI 6.90 to 11.10 months) for the control group. Estimated survival rates for 1, 3 and 5 years were better in the TACE group (50.9%, 33.8%, 21.5%; respectively) than the control group (33.3%, 17.0%, 8.5%, respectively; log rank P = .0094).

Conclusions

Postoperative TACE enhances the effect of liver resection combined with PVTT removal for HCC patients with PVTT.     

Liver transplantation is an alternative treatment of hepatocellular carcinoma beyond the Milan criteria

Background

The decision to perform liver transplantation (LT) or liver resection (LR) for patients with hepatocellular carcinoma (HCC) who are beyond the Milan criteria remains controversial.

Methods

We retrospectively analyzed outcome data for 179 patients with HCC beyond the Milan criteria who were treated with LR (n = 135) or LT (n = 44). Univariate and multivariate Cox proportional hazard models were established. Kaplan-Meier survival curves were generated, and a log-rank test was performed to compare group survival status.

Results

Patients who underwent LR group were significantly older, had a lower TNM stage, and were more likely to have unilateral disease and noncirrhotic liver. Significantly more patients in the LR group had recurrence (53.3% vs 29.5%) or died (61.5% vs 43.2%) than patients in the LT group. Recurrence-free survival rates were 11.9% for the LR group and 61.5% for the LT group. The median overall survival duration showed no statistically difference between the LR group (28.0 months) and the LT group (50.0 months).

Conclusions

LT may be the better choice for patients with HCC beyond the Milan criteria.     

The relationship between recurrences and immunosuppression on living donor liver transplantation for hepatocellular carcinoma

Objectives

Living donor liver transplantation (LDLT) offers timely transplantation for patients with hepatocellular carcinoma (HCC). If ABO-incompatible LDLT is feasible, the needs for pretransplantation treatments may be eliminated. It is known that negative impacts of immunosuppression are limited among LDLT for HCC, however, we believe that excessive immunosuppression is one of the risk factors for recurrence. We compared the impacts of immunosuppression for LDLT with hepatectomy outcomes for HCC.

Methods

From 1991 to 2010, we performed 144 LDLTs including 14 patients with HCC. Seven met the Milan criteria. Immunosuppressive therapies were based on tacrolimus plus methylprednisolone plus CD25 antibody. For ABO-incompatible cases, we also used mycophenolate mofetil and rituximab. Five cases underwent strong imunosuppressive therapy (steroid pulse or rituximab) within 180 days. In addition, we performed hepatectomy for 180 HCC cases from 1997 to 2010.

Results

Overall survival rates of the LDLT cohort and hepatectomy groups were similar, but disease-free 5-year survival rates (DFS) of the LDLT cohort were significantly better than those of the hepatectomy group (total = 54.4% versus 27.4%, within the Milan criteria cases, 71.4% versus 33.8%). Thus, the negative impact of immunosuppression on recurrence was less than the benefit of a whole liver resection. Among strongly immunosuppressed cases, 5-years DFS rates were significantly worse than among other immunosuppressed cases (20.0% versus 76.2%). Upon univariate analysis, the factors associated with HCC recurrence were alpha-fetoprotein levels and steroid doses within 180 days, but multivariate analysis did not show a predictor for recurrence.

Conclusion

Patients who are strongly immunosuppressed may have several negative impacts for recurrences. More careful indications must be selected for ABO-incompatible cases.     

Multicenter prospective randomized trial comparing modified Limberg flap transposition and Karydakis flap reconstruction in patients with sacrococcygeal pilonidal disease

Background

There is still no consensus as to the optimal treatment for sacrococcygeal pilonidal disease (SPD). Many recommend off-midline closure, if any excisional procedure is to be selected.

Methods

The authors prospectively studied 145 patients with SPD who presented at 3 hospitals. Patients were randomly assigned to undergo either modified Limberg flap (MLF) transposition (n = 72) or Karydakis flap reconstruction (n = 73). Surgical findings, complications, recurrence rates, and degree of patient satisfaction, evaluated via a standardized telephone interview, were compared.

Results

Operation time was longer in the MLF group. There were no significant differences between the two groups in terms of complication rate, length of stay, or recurrence rate. Patients in the Karydakis group reported feeling completely healed more quickly postoperatively. The two groups reported similar rates of satisfaction. Mandatory patient withdrawal from a given study arm because of the orifice straying from the midline occurred more frequently in the Karydakis group.

Conclusions

The MLF technique and the Karydakis procedure appear to generate comparable outcomes. With laterally situated orifices, however, the applicability of the Karydakis method may be limited.     

Clinicopathologic characteristics and prognosis of young patients with breast cancer

Background

The aim was to describe the clinicopathological features and prognosis of young patients with breast cancer.

Patients and Methods

We reviewed the records of 1478 consecutive patients aged ≤50 years with first diagnosis of invasive breast cancer referred to surgery from January 1999 to March 2005. A total of 174 patients were aged <35 years (group I) and 1304 were aged 35-50 years (group II).

Results

Compared with patients of group II, patients of group I had a higher percentage of tumors classified as estrogen receptors (ER) negative, progesterone receptors (PR) negative, with a Ki-67 labeling index ≥20% of the cells. The 5-year survival of group I was 78.3% as compared with 84.2% for group II (P = 0.006).

Conclusion

Compared with patients aged between 35 and 50 years, patients aged <35 years have a greater chance of having an endocrine-unresponsive tumor and a significantly poor prognosis.     

Living donor liver transplantation for hepatocellular carcinoma

Background

Liver transplantation is a widely accepted modality in the treatment of hepatocellular carcinoma (HCC). In our center, patients with HCC limited to the liver without macrovascular invasion are accepted as candidates for living donor liver transplantation (LDLT). The aim of this study was to describe the patient characteristics and outcomes at a single institution to analyze the impact of our criteria on the survival of HCC patients.

Patients and Methods

We reviewed the medical records of all HCC (n = 105) patients who underwent liver transplantation in our institution. We excluded deaths in the early postoperative period and deceased donor liver transplantation (DDLT) patients, leaving 74 subjects (65 males and 9 female). Their median age was 53 years (range, 19-69). Univariate Kaplan-Meier and multivariate Cox proportional hazards models were used to analyze overall and disease-free survivals.

Results

Thirty-two (43%) patients were within the Milan criteria, and 42 (57%) exceeded them. One- and 2-year overall survival rates for patients within versus exceeding the Milan criteria were 72% versus 68% and 61% versus 58%, respectively. One- and 2-year disease-free survival rates for patients within versus exceeding the Milan criteria were 72% versus 68% and 60% versus 55%, respectively (P > .05). Tumor recurrence rates for patients within versus exceeding the Milan criteria were 0% versus 36%, respectively (P = .0002). Alpha-fetoprotein level was the only predictor of overall survival; alpha-fetoprotein level and tumor differentiation were predictors of disease-free survival.

Conclusion

Although higher recurrence rates have been observed among patients exceeding the Milan criteria, LDLT is the only treatment option for the patients in countries with limited sources of cadaveric organs. As a general principle, we believe that the use of cadaveric donor liver grafts is not suitable for patients who exceed these criteria.     

Selective Transarterial Chemoembolization of Advanced Hepatocellular Carcinomas: A Reasonable Palliative Option

Background

The purpose of this study was to provide information concerning the performance of selective transarterial chemoembolization (TACE) as a palliative treatment in patients with hepatocellular carcinoma (HCC), also in the case of multifocal lesions.

Patients and methods

We reviewed prospectively collected data on 43 patients with cirrhosis and HCC who underwent selective TACE as a palliative treatment. Patients were assigned to one of two groups: (1) those with one to three HCC lesions, and (2) those with four or more HCC lesions.

Results

One hundred and two TACE sessions were applied in 43 patients. There were 39 men and 4 women with a mean age of 65.5 ± 8.273 years. Alpha fetoprotein levels were elevated to a median value of 73.8 U/mL prior to first TACE (range, 1.5-25615 U/mL). Fourteen patients underwent one session, and 29 patients from two to eight TACE sessions. Bilobar HCC distribution prior to initial TACE was evident in 40% of the patients. Solitary HCC was radiologically diagnosed in 14 patients. Twenty-seven patients were assigned to group 1 and 16 patients to group 2. No significant differences were found between the two groups concerning the number of TACE sessions and the severity of liver cirrhosis. Currently 12 patients are alive after a median follow-up of 25 months (range, 3-84 months). Three- and 5-year survival rates according to patient groups were 45% and 19%, and 42% and 11% for the patients' groups 1 and 2, respectively (P = .87).

Conclusions

HCC patients without a curative therapy option may benefit from palliative TACE, also in the case of multifocal lesions.     

Primary versus salvage living donor liver transplantation for patients with hepatocellular carcinoma: impact of microvascular invasion on survival

Objective

Salvage liver transplantation (LT) has been proposed for patients with a small hepatocellular carcinoma (HCC) and preserved liver function. Few reports have been issued on salvage LT in a living-donor (LD) LT setting. Therefore, we performed this study to evaluate differences in tumor invasiveness and other risk factors on survival after salvage versus primary LDLT.

Methods

Between September 1996 and December 2008, 324 patients with HCC underwent LT. We excluded 138 patient from the analysis, leaving 186 HCC patients for analysis, including 17 (9.1%) who had undergone earlier resection, the salvage LDLT cohort. The other 169 patients underwent primary LDLT.

Results

Intrahepatic metastasis, Edmonson-Steiner histologic grade, microscopic vascular invasion, and preoperative serum alpha-fetoprotein levels significantly influenced tumor recurrence. Microscopic vascular invasion, intrahepatic metastasis, Edmonson-Steiner histologic grade, and treatment by salvage LDLT were significantly associated with poor patient survival univariate analysis. However, only microscopic vascular invasion was significant on multivariate analysis. The treatment modality (primary or salvage LDLT) was not observed to affect overall or disease-free survival significantly on multivariate analysis. Disease-free survival was significantly better in the primary than in the salvage LDLT group. Furthermore, patients in the primary LDLT group tended to show better survival. However, when stratified by the presence or absence of microscopic vascular invasion, no significant group difference was found for overall or disease-free survival among those without versus with microscopic vascular invasion.

Conclusions

Five-year overall survival after primary versus salvage LDLT were similar when differences in tumor pathologic features, such as microscopic vascular invasion, were taken into account. Multivariate analysis showed that the treatment itself was not a significant prognostic factor for survival.     

Effect of Low-Dose Rapamycin on Tumor Growth in Two Human Hepatocellular Cancer Cell Lines

Aim

Liver transplantation is the best treatment for patients with early hepatocellular carcinoma (HCC) and cirrhosis. A limiting factor for long-term survival remains posttransplant tumor recurrence. Thus, there is widespread discussion about the role of various immunosuppressive agents. The newly developed immunosuppressive drug rapamycin may aid to lower recurrence rates. We investigated the efficiency of rapamycin as compared with previous immunosuppressants in a tumor cell model.

Methods

We studied two HCC cell lines for cell-cycle and proliferation analyses after treatment with rapamycin or other immunosuppressants. To elucidate the underlying molecular signaling pathway, we performed Western blotting for phosphorylated p70 S6 kinase protein expression.

Results

Low-dose rapamycin inhibited tumor cell growth at doses of 1, 5, and 10 ng/mL, while standard immunosuppressants stimulated growth. A rapamycin dose of 20 ng/mL showed a marked decrease in the growth inhibition of both HCC cell lines compared to low-dose administration.

Conclusion

Rapamycin in low doses inhibited the growth of two HCC cell lines in vitro. Inhibition of tumor cell growth was observed with a high dose of rapamycin (20 ng/mL), which appears to be the dividing line between growth and inhibition. We postulated that at higher doses the immunosuppressive effect of rapamycin is overrode by its antitumor effects.     

New onset arrhythmias after the extracardiac conduit Fontan operation compared with the intraatrial lateral tunnel procedure: early and midterm results

Background

Arrhythmias are one of the main causes of postoperative morbidity superseding Fontan operations. Comparative data on the incidence of sinus node dysfunction after the extracardiac Fontan operation (ECFO) and the intraatrial lateral tunnel Fontan operation (LTFO) are very limited and controversial. The aim of this study was to evaluate whether ECFO decreases the risk of postoperative arrhythmias compared with LTFO.

Methods

Seventy-four consecutive patients received either an LTFO (n = 29, 5 recordings in 1992 to 9 recordings in 1997) or an ECFO (n = 45, 11 recordings in 1995 to 5 recordings in 2001). The rhythm was documented preoperatively and postoperatively with standard electrocardiogram (ECG) recording and ECG monitoring. During follow-up all patients had 2-8 (median 3) standard ECG recordings per year. Additionally 45 patients (65%) had a Holter ECG at least once a year.

Results

Median follow-up post-ECFO was 4.4 years (1.6-7.2) and post-LTFO it was 7.9 years (5.4-11.1). There were 5 early deaths (3 LTFO, 2 ECFO) and 1 late death (LTFO) (total mortality 8%). Sinus rhythm persisted in 37 ECFO patients (86%) as compared with 13 LTFO patients (50%) (p < 0.001). The incidence of new onset supraventricular tachyarrhythmias (SVTs) post-ECFO compared with LTFO was lower: 5 patients (11%) versus 11 patients (38%) early postoperatively (p < 0.001) and none versus 7 patients (27%) during follow-up (p < 0.001), respectively. Early postoperatively 10 LTFO patients (34%) and another 3 patients during follow-up required permanent pacemaker implantation due to bradyarrhythmias, but none of the ECFO patients required this.

Conclusions

Our data suggest that ECFO decreases the incidence of postoperative new onset arrhythmias during early and midterm follow-up compared with LTFO.     

Living Donor Liver Transplantation for Hepatocellular Carcinoma: Long-Term Results Compared With Deceased Donor Liver Transplantation

Objective

Living donor liver transplantation (LDLT) may represent a valid therapeutic option allowing several advantages for patients affected by hepatocellular carcinoma (HCC) awaiting orthotopic liver transplantation (OLT). However, some reports in the literature have demonstrated worse long-term and disease-free survivals among patients treated by LDLT than deceased donor liver transplantation (DDLT) for HCC. Herein we have reported our long-term results comparing LDLT with DDLT for HCC.

Patients and Methods

Among 179 patients who underwent OLT from January 2000 to December 2007, 25 (13.9%) received LDLT with HCC 154 (86.1%) received DDLT. Patients were selected based on the Milan criteria. Transarterial chemoembolization, radiofrequency ablation, percutaneous alcoholization, or liver resection was applied as a downstaging procedure while on the waiting list. Patients with stage II HCC were proposed for LDLT.

Results

The overall 3- and 5-year survival rates were 77.3% and 68.7% versus 82.8% and 76.7% for LDLT and DDLT recipients, respectively, with no significant difference by the log-rank test. Moreover, the 3- and 5-year recurrence-free survival rates were 95.5% and 95.5% (LDLT) versus 90.5% and 89.4% (DDLT; P = NS).

Conclusions

LDLT guarantees the same long-term results as DDLT where there are analogous selection criteria for candidates. The Milan criteria remain a valid tool to select candidates for LDLT to achieve optimal long-term results.     

Long-term results after surgical treatment of nonparasitic hepatic cysts

Background

Studies evaluating surgical success in patients with benign liver cysts focus on cyst recurrence. The aim of this study was to evaluate the efficacy of surgical treatment with regard to clinical complaints.

Materials and methods

Between 1995 and 2007, 99 patients (M:F 1:7.25) with symptomatic, benign, nonparasitic liver cysts (77 simple liver cysts [SLCs], 22 polycystic liver disease [PCLD]) underwent surgical treatment (77% laparoscopic surgery, 23% open surgery). Perioperative parameters (including morbidity) were evaluated. Moreover, a questionnaire was completed by 65 patients monitoring subjective complaints focusing on abdominal pain, vegetative symptoms, and dyspnea pre- and postoperatively (mean follow-up 76 months).

Results

Severe complications occurred in 7 patients. Abdominal pain, vegetative symptoms, and dyspnea were significantly improved in SLC patients. In PCLD patients abdominal pain and dyspnea were significantly decreased, whereas vegetative symptoms were unaffected by surgery. The symptom recurrence rate for SLC patients was significantly lower compared with PCLD patients (41% vs 66.6%).

Conclusion

Indications for surgical treatment of PCLD should be well considered and limited to a selected group of patients.