Single HCC in Cirrhotic Patients: Liver Resection or Liver Transplantation? Long-term Outcome According to an Intention-to-treat Basis

Background

Compensated cirrhotic patients with single hepatocellular carcinoma (HCC) ≤5 cm may benefit from both liver resection (LR) and liver transplantation (LT); however, the better 10-year actuarial survival of the two treatments remains unclear. We aimed to assess the long-term outcome of cirrhotic patients with single HCC ≤5 cm treated either with LR or LT on an intention-to-treat basis.

Methods

A total of 217 cirrhotic patients with single HCC ≤5 cm were evaluated at our department: 95 were treated with LR (LR group), and 122 were included on the waiting list for LT (LT group). Patients in the LR group were divided into very early HCC (tumor size ≤2 cm) and early HCC (tumor size >2 cm). Median follow-up was 5.3 (range 0.1–18) years.

Results

Tumor recurrence was 72 % in the LR group versus 16 % in the LT group (p < 0.001). 1-, 5-, and 10-year cumulative risk of recurrence was 18, 69, and 83 % in the LR group versus 4, 18, and 20 % in the LT group (p < 0.001). Ten-year actuarial survival was 33 % in the LR group versus 49 % in the LT group (p = 0.002). At HCC recurrence, 27.3 % were included on the waiting list for salvage transplantation (very early HCC group) versus 15.1 % (early HCC group) (p = 0.2). After salvage transplantation, HCC recurrence was 0 % (very early HCC group) versus 40 % (early HCC group) (p = 0.2). No significant differences were observed in 1-, 5-, and 10-year actuarial survival between the very early HCC group and the LT group (95, 55, and 50 % vs. 82, 62, and 50 %).

Conclusions

LR should be the treatment of choice for cirrhotic patients with very early HCC.     

Impact of Spontaneous Hepatocellular Carcinoma Rupture on Recurrence Pattern and Long-term Surgical Outcomes after Partial Hepatectomy

Background

The clinical significance of spontaneous hepatocellular carcinoma (HCC) rupture association with recurrence pattern and long-term surgical outcomes remains under debate. We investigated the impact of spontaneous HCC rupture on recurrence pattern and long-term surgical outcomes after partial hepatectomy.

Methods

From 2000 to 2012, 119 patients with diagnosed ruptured HCC were reviewed. To compare outcomes between staged hepatectomy in spontaneously ruptured HCC and hepatectomy in non-ruptured HCC, we performed propensity score-matching to adjust for significant differences in patient characteristics. Overall survival, disease-free survival, and recurrence pattern were compared between the matched groups.

Results

Forty-four patients with newly diagnosed ruptured HCC and Child A class were initially treated with transcatheter arterial embolization for hemostasis. Three patients underwent emergency laparotomy, 18 underwent staged hepatectomy, and 23 received transarterial chemoembolization (TACE) alone after transcatheter arterial embolization. Among the 23 patients treated with TACE alone, 10 had resectable tumors. The staged hepatectomy group shows significantly higher overall survival with TACE alone than the resectable tumor group (P < 0.001). After propensity score-matching, overall survival, disease-free survival, and recurrence pattern were not significantly different between the ruptured HCC with staged hepatectomy group and the non-ruptured HCC with hepatectomy group. Peritoneal recurrence rates were similar at 14.3 % versus 10.0 %, respectively (P = 0.632).

Conclusions

Patients with spontaneously ruptured HCC with staged hepatectomy show comparable long-term survival and recurrence pattern as patients with non-ruptured HCC having similar tumor characteristics and liver functional status. Thus, spontaneous HCC rupture may not increase peritoneal recurrence and decrease long-term survival after partial hepatectomy.     

Complete Necrosis After Transarterial Chemoembolization Could Predict Prolonged Survival in Patients with Recurrent Intrahepatic Hepatocellular Carcinoma After Curative Resection

Background

We explored the predictors of response to transarterial chemoembolization (TACE) in patients with recurrent intrahepatic hepatocellular carcinoma (HCC) after hepatectomy and investigated the survival of these patients according to the response to TACE.

Methods

We analyzed data from 199 consecutive HCC patients who underwent curative liver resection and who later received repeat TACE for intrahepatic HCC recurrence.

Results

Of 199 patients, 139 (69.8%) achieved complete necrosis (CN) of HCC after repeated TACE (mean TACE session number, 1.3) and the other 60 (30.2%) (non-CN group) did not achieve CN. At hepatectomy, the CN group showed significantly smaller proportions of tumor capsular invasion, microvascular invasion, and pathologic tumor–node–metastasis stage III or IV HCCs. At first TACE, the CN group showed a significantly greater proportion of patients with time to recurrence ≥ 1 year, Child–Pugh class A, serum alpha-fetoprotein (AFP) levels < 200 ng/mL, tumor size < 3 cm, solitary tumors, and nodular tumor types; portal vein invasion were less common than seen in the non-CN group. After multivariate analysis, tumor size < 3 cm and a single tumor at first TACE were independently related to attainment of CN after TACE. Median survival after first TACE was significantly longer in the CN group (48.9 versus 17.0 months). In a Cox regression model, CN after TACE was an independent predictor of favorable survival outcome after first TACE.

Conclusions

CN after repeat TACE for postresection intrahepatic recurrence was attained more commonly in patients with smaller tumor size and lower tumor number at first TACE and favored longer survival in recurrent patients.     

Milan Criteria, Multi-nodularity, and Microvascular Invasion Predict the Recurrence Patterns of Hepatocellular Carcinoma After Resection

Aims

This study aims to evaluate the risk factors for tumor recurrence beyond the Milan criteria (MC) for patients with hepatocellular carcinoma (HCC) after surgical resection (SR) in which salvage liver transplantation is relatively contraindicated.

Methods

A total of 447 patients who underwent SR for HCC were enrolled consecutively. Among them, 248 and 199 patients were within the Milan criteria and beyond the Milan criteria (BMC group), respectively. Overall survival, recurrence, and disease-free survival were analyzed by multivariate analysis.

Results

After a median follow-up of 34.4 months, 130 patients died. Microvascular invasion, higher Edmondson stage of tumor cell differentiation, BMC group, and no anti-viral therapy were associated with poor overall survival. Multi-nodularity, higher Edmondson stage, BMC group, and no anti-viral therapy were independent risk factors for tumor recurrence, while BMC group and no anti-viral therapy were independent risk factors for disease-free survival. The Milan criteria, multi-nodularity, and microvascular invasion were used to stratify the patients into low-, medium-, and high-risk groups for tumor recurrence outside the MC and showed statistical significance (low vs. medium, p?=?0.011; low vs. high, p?<?0.001; medium vs. high, p?=?0.009).

Conclusions

The combination of the MC, multi-nodularity, and microvascular invasion predict the post-operative recurrence of HCC and may provide a roadmap for further treatment.     

The Postresection Alpha-Fetoprotein in Cirrhotic Patients with Hepatocellular Carcinoma. An Independent Predictor of Outcome

Background

The postresection alpha-fetoprotein (AFP) in cirrhotic patients with hepatocellular carcinoma (HCC) may predict overall survival (OS) and recurrence beyond Milan criteria (MC) among the subgroup of initially transplantable patients.

Methods

All patients with cirrhosis resected for HCC between January 1990 and December 2010 in a single institution and presenting a serum AFP value?>?15 ng/ml at diagnosis were included. The postresection AFP was analyzed as a dichotomized variable: normalization (norm + group) or not (norm ? group) within the 90-day postresection period.

Results

Among 271 resected patients, 141 patients (52 %) had a level of serum AFP?≥?15 ng/ml at diagnosis. Five-year OS and median survival were 42 % and 52 months in group norm + versus 20 % and 23 months in the group norm ? (P?=?0.009). On multivariate analysis, the absence of AFP normalization was an independent factor of poor OS as well as microvascular invasion, and satellites nodules. Among theoretically transplantable patients, independent predictors of recurrence beyond MC were the absence of AFP normalization (risk ratio (RR) 5.02 [1.53–16.34]) and microvascular invasion (RR 4.76 [1.42–15.34]).

Conclusion

The postresection AFP has an independent prognostic value. Transplantable patients resected for HCC without 90-day AFP normalization should be discussed for early liver transplantation.     

Outcomes of lymphadenectomy for lymph node recurrence after esophagectomy or definitive chemoradiotherapy for squamous cell carcinoma of the esophagus

Objective

The aim of this study was to determine the significance of lymphadenectomy for recurrence after treatment for esophageal squamous cell carcinoma.

Methods

Short- and long-term outcomes of 24 patients who underwent lymphadenectomy for recurrence in 3 hospitals between April 2004 and March 2013 were retrospectively analyzed. There were 17 cases with lymph node recurrence after esophagectomy (11 cervical, 4 mediastinal, and 2 abdominal node recurrences) and 7 cases with remnant or recurrent lymphatic diseases after definitive chemoradiotherapy (3 cervical, 1 mediastinal, and 3 abdominal node recurrences).

Results

Three minor complications were observed among 24 patients and the median postoperative hospital stay was 7 days. The 3-year progression-free and overall survivals of patients who underwent secondary lymphadenectomy for recurrence after esophagectomy were 51.5 and 75.5 %, respectively. The overall survival of patients with cervical node recurrence was significantly better than that of patients with mediastinal or abdominal node recurrence in this group (P = 0.0097). The median progression-free and overall survivals of patients who underwent salvage lymphadenectomy after definitive chemoradiotherapy were 2 and 15 months, respectively. Although only 1 patient experienced local recurrence after secondary lymphadenectomy, locoregional failures occurred in 6 of 7 patients who underwent salvage lymphadenectomy after definitive chemoradiotherapy.

Conclusion

Secondary or salvage lymphadenectomy can be performed safely in the selected patients. Secondary lymphadenectomy achieves locoregional disease control and results in a favorable long-term outcome, particularly for cervical node recurrence. Further large-scale cohort studies are needed to determine the prognostic significance of salvage lymphadenectomy after definitive chemoradiotherapy.     

High risk of lung metastasis after resection of hepatocellular carcinoma more than 7 cm in diameter

Purpose

The relationship between the tumor size and organs of recurrence was analyzed to identify a high-risk group for the extrahepatic recurrence of hepatocellular carcinoma (HCC) after resection.

Methods

A total of 544 patients with HCC underwent primary surgical resection for HCC between 2001 and 2010. Of these, 293 patients had a solitary tumor but no macroscopic vascular invasion. The prognostic factors for the overall survival and relapse-free survival were analyzed among these 293 patients. The recurrent organs and frequency of recurrence were also examined.

Results

The analysis of the 293 patients showed that both the overall and relapse-free survival rates of the patients with a large tumor (>7 cm in diameter) were significantly worse than those of the patients with a tumor <7 cm. The incidence of lung metastasis was remarkably high in the group of patients with tumors more than 7 cm (24.0 %), in comparison to those with tumors <7 cm. A multivariate analysis revealed that the tumor size was the only independent risk factor for lung metastasis.

Conclusions

The patients with large HCC tumors more than 7 cm in diameter were at high-risk for a poor prognosis due to a high percentage of lung metastasis, even if there was no macroscopic vascular invasion.     

Infection with Hepatitis C Virus is an Adverse Prognostic Factor after Liver Resection for Early-stage Hepatocellular Carcinoma

Introduction

Recent data support liver resection (LR) as first-line approach in patients with preserved liver function who have resectable/transplantable hepatocellular carcinoma (HCC). This study was designed to evaluate the outcome of LR in patients with transplantable HCC.

Methods

Between 1998 and 2009, 75 patients (65 men, mean age 61 ± 11 years) with HCC eligible for liver transplantation (LT) underwent LR. The underlying hepatic disease was related to hepatitis C (HCV) in 30 (40 %) patients, hepatitis B (HBV) in 15 (20 %) patients, alcohol abuse in 26 patients (36 %) and other in 10 patients (13 %). Fifty-five (73 %) patients had cirrhosis. Intermittent clamping of the hepatic pedicle was used in 41 (55 %) patients. Treatment of recurrence by salvage LT was performed in 6 (8 %) patients.

Results

Operative morbidity and mortality rates were 37 and 5  % respectively. At 1, 3, and 5 years, overall (OS) and disease-free (DFS) survival rates were 81, 69,55 and 56, 31, and 21 %, respectively. On multivariate analysis, HCV infection was the only independent factor associated with decreased OS (p = 0.02). On multivariate analysis, HCV infection (p = 0.05) and intermittent hepatic pedicle clamping (p = 0.003) were associated with decreased DFS. The 1-, 3-, and 5-year OS and DFS rates in patients with HCV-related HCC were 69, 53, 38 and 50, 18, and 9% respectively.

Conclusions

Overall and disease-free survival after liver resection in patients with HCV-related HCC and preserved liver function is poor. Primary LT should be offered to these patients.     

Sorafenib treatment is save and may affect survival of recurrent hepatocellular carcinoma after liver transplantation

Introduction

Recurrent hepatocellular carcinoma (HCC) after liver transplantation (LT) is a rare but challenging condition. In most cases, the recurrent tumor is presented with extrahepatic spread. Therefore, systemic treatment with sorafenib has to be assessed. Because of a plethora of possible drug interactions, e.g., with immunosuppressant or anti-infective therapy, safety and feasibility of sorafenib treatment requires special attention.

Materials and methods

We retrospectively analyzed 18 patients who suffered from recurrent advanced HCC after LT between January 2002 and December 2010 at the University Hospital Heidelberg regarding safety of sorafenib treatment and survival.

Results

Results showed that 8 patients were eligible for treatment with sorafenib showing a median time to progression (TTP) of 4.5 months and an overall survival of 9 months. Most common side effects were grades I and II diarrhea and hand–foot syndrome (HFS) which could be managed by sorafenib dose reduction. No grade III or IV adverse events (AEs) were noticed. No patient had to discontinue treatment due to AEs. The ten patients not amenable for sorafenib treatment, due to initial poor performance status or its deterioration after first line treatment, were treated with surgical resection (n?=?3), locoregional therapies (n?=?1), or palliative radiation therapy (n?=?1). They showed a median overall survival of 2.3 months.

Conclusion

Sorafenib may represent a therapeutic option for recurrent HCC after LT with manageable side effects. The clinical benefit of sorafenib in this setting is promising but needs to be confirmed in a prospective randomized trial.     

Locoregional Therapy-Induced Tumor Necrosis as a Predictor of Recurrence after Liver Transplant in Patients with Hepatocellular Carcinoma

Background

Patients with hepatocellular carcinoma (HCC) often undergo locoregional therapy before liver transplant either to downstage the tumor or as bridge therapy. Our goal was to assess the risk factors for posttransplant tumor recurrence, specifically the extent of necrosis induced by locoregional therapy.

Methods

We conducted a hospital-based retrospective analysis of 100 patients with HCC who received a liver transplant, 86 of whom had received pretransplant locoregional therapy. We evaluated various patient- and tumor-related parameters to determine the risk factors for recurrence. Furthermore, we grouped patients by the degree of tumor necrosis after locoregional therapy and identified the factors that were associated with a favorable tumor response.

Results

Initial tumor extent beyond the University of San Francisco (UCSF) criteria, microvascular invasion, and attainment of less than 90% tumor necrosis after locoregional therapy were independent risk factors for tumor recurrence. In addition, there was a significant correlation between the tumor necrosis percentage and disease-specific survival rate. Among patients whose tumors initially exceeded the UCSF criteria, those with extensive locoregional therapy-induced tumor necrosis had lower recurrence rates. All recurrences after transplant occurred within 3 years, and recurrence rates in patients with extensive tumor necrosis at 1, 2, and 3 years were 3%, 6%, and 10%, respectively. Female gender and a solitary tumor were independently associated with extensive tumor necrosis.

Conclusions

In HCC patients who are transplant candidates and undergo pretransplant locoregional therapy, the degree of induced tumor necrosis affects both tumor recurrence and survival rate.     

Response to Therapy as a Criterion for Awarding Priority to Patients With Hepatocellular Carcinoma Awaiting Liver Transplantation

Background

How to prioritize patients with hepatocellular carcinoma (HCC) for liver transplantation (LT) remains controversial. This study was designed to assess the effectiveness of a policy for prioritizing HCC patients according to their response to pre-LT therapy.

Methods

The study period was from 2000 to 2008. Dropout criteria included macroscopic vascular invasion, metastases, and poorly differentiated grade at pre-LT biopsy. A specific treatment algorithm was adopted to treat HCC before LT, and the effect of treatment was evaluated 3 months after listing or after the diagnosis of HCC for patients diagnosed while already on the waiting list. Patients were divided into two groups: group 1, patients with disease that completely or partially responded to therapy; and group 2, patients with stable, progressive, or untreatable disease. Group 2 patients were prioritized for LT unless full restaging and repeat biopsy identified dropout criteria.

Results

At the 3-month visit, 62 HCC patients (42%) were assigned to group 2 and 85 (58%) to group 1. Eleven of 12 dropouts due to tumor progression came from group 2 (P < 0.01). Response to therapy was the sole predictor of dropout probability, independent of tumor stage (competing risk analysis). The 42 patients in group 2 who were transplanted had much the same 3-year post-LT survival rate as the 57 transplanted patients in group 1 (with survival rates of 82% and 83%, respectively; P > 0.05), but a slightly higher risk of post-LT HCC recurrence (13% and 2%, respectively; P = 0.04).

Conclusions

Response to therapy is a potentially effective tool for prioritizing HCC patients for LT.     

Lens Culinaris Agglutinin-Reactive Fraction of Alpha-Fetoprotein as a Marker of Prognosis and a Monitor of Recurrence of Hepatocellular Carcinoma After Curative Liver Resection

Background

The aim of this study was to determine the role of Lens culinaris agglutinin-reactive fraction of alpha-fetoprotein (AFP-L3) as a prognostic marker and a monitor marker of recurrence after curative resection of hepatocellular carcinoma (HCC).

Methods

From December 2002 to May 2004, 395 consecutive patients with HCC who underwent curative partial hepatectomy were included in the study. The tumor characteristics and clinical outcomes of patients with positive preoperative and postoperative AFP-L3 were compared with those with negative results.

Results

A high ratio of AFP-L3 to total AFP was an indicator of pathologic aggressiveness. Patients with positive preoperative AFP-L3 had significantly earlier recurrence (median time to recurrence 22.0 ± 2.4 months vs 45.0 ± 6.9 months, P < .001) when compared with those with negative preoperative results. Significantly more patients with continuously positive or negative-turn-positive AFP-L3 results after surgery developed recurrence, particularly distant metastases, when compared with patients with continuously negative AFP-L3 results. The overall and disease-free survivals were significantly shorter in the positive than the negative preoperative AFP-L3 group. The overall and disease-free survivals were significantly shorter in the continuously positive and the negative-turn-positive than the continuously negative postoperative AFP-L3 group.

Conclusion

Positive preoperative AFP-L3 and continuously positive or negative-turn-positive AFP-L3 results after surgery predicted a more aggressive tumor behavior, higher tumor recurrence, and poorer clinical outcomes. HCC patients with an increased proportion of AFP-L3 to total AFP should be more aggressively treated and closely followed-up.     

Protein Induced by Vitamin K Antagonist-II (PIVKA-II) Is a Reliable Prognostic Factor in Small Hepatocellular Carcinoma

Background

Hepatocellular carcinoma (HCC) <2 cm in diameter has a favorable prognosis. Therefore surgical resection of small HCC is associated with good outcomes. However, the predisposing factors of prognosis following resection of HCC remain ill-defined. The aims of the present study were to identify the clinicopathologic characteristics and outcomes of patients with small HCC and analyze the predisposing factors for tumor recurrence after surgery.

Methods

We retrospectively reviewed 180 patients with small HCC who underwent hepatectomy between 2006 and 2010. Independent predictors of tumor recurrence were identified with Cox regression analysis.

Results

The 1-year, 3-year, and 5-year disease-free survival rates and overall survival rates were 83.7, 68.0, 65.3, and 98.9, 96.5, 92.7 %, respectively. Multivariate analysis reported that protein induced by the vitamin K antagonist-II (PIVKA-II) ≥200 mAU/mL, alkaline phosphatase (ALP) ≥80 IU/mL, and microvascular invasion were important predisposing factors for tumor recurrence. Elevated serum PIVKA-II level was associated with microvascular invasion in small HCC, which was a powerful predisposing factor.

Conclusions

Although small HCC is generally associated with a good prognosis, serum PIVKA-II level ≥200 mAU/mL, ALP ≥ 80 IU/L, and microvascular invasion were predisposing factors for tumor recurrence. These factors can be used to stratify patients with respect to recurrence after resection. Elevated PIVKA-II was closely associated with microvascular invasion in small HCC. These data emphasize the importance of PIVKA-II in small HCC.     

Laparoscopic left hepatectomy with tumor thrombectomy in patients with hepatocellular carcinoma concomitant with advanced portal vein tumor thrombus

Background

Although laparoscopic hepato-biliary-pancreatic surgery has been widely adopted, use of laparoscopic resection for hepatocellular carcinoma (HCC) with advanced portal vein tumor thrombus (PVTT) is uncommon because of the complications involved.

Methods

From June 2010 through November 2013, 200 laparoscopic hepatectomies were performed. We report the short-term outcome of laparoscopic hepatectomy for HCC with advanced PVTT in 3 patients. Video presentation is a demonstration of the operative procedures employed in Case 3. In this case, the left hepatic artery and left hepatic duct were divided before tumor thrombectomy, and the bifurcation of the portal vein was clearly visible.

Results

Three female patients with HCC concomitant with PVTT in the portal trunk or the opposite branch underwent laparoscopic left hepatectomy with tumor thrombectomy using a laparoscopy-assisted technique (1 patient) or pure laparoscopic technique (2 patients). The median operative time was 592 min (range, 555–891 min), and median estimated blood loss was 1182 ml (range, minimal amount–4800 ml). The median length of hospital stay was 19 days (range, 9–22 days), and there was no postoperative mortality. In Case 1, recurrent tumors developed in the residual lobe after curative resection, and the patient died 10 months after the surgery despite treatment with sorafenib and transcatheter arterial chemoembolization. In Case 2, the patient survived for 10 months after curative resection without tumor recurrence. In Case 3, the patient was treated with sorafenib 1 month after palliative resection; she survived for 4 postoperative months, during which decreased tumor marker levels were observed.

Conclusions

Laparoscopic hepatectomy for HCC with advanced PVTT is a safe and feasible procedure in selected patients, when performed by surgeons with expertise in hepatic surgery and minimally invasive techniques. Although these patients cannot be cured by surgery alone, early adjuvant therapy followed by laparoscopic surgery might contribute to a good outcome.     

R1 Hepatectomy With Exposure of Tumor Surface for Centrally Located Hepatocellular Carcinoma

Background

Hepatectomy with exposure of tumor surface (a special type of R1 resection) provides a chance of cure for selected patients with centrally located hepatocellular carcinoma (HCC) that is adherent to or compresses major vessels. However, the operative indications, safety, and patient outcomes are not well defined.

Methods

We performed hepatectomy for removal of complex centrally located HCC using a selective and dynamic region-specific vascular occlusion technique. Between May 2006 and March 2012, a total of 118 patients underwent resection with exposure of tumor surface (exposure group) and 169 underwent conventional hepatectomy (without exposure of the tumor and vascular surface). The short- and long-term outcomes of patients were evaluated and compared.

Results

The postoperative recovery of liver function was comparable between the two groups. Bile leakage occurred in five patients, all in the exposure group. The 1-, 3-, and 5-year recurrence-free survival rates were 74.4, 45.6, and 30.1 % in the exposure group and 80.9, 57.2, and 31.7 % in the control group (p = 0.041). Corresponding overall survival rates were 92.3, 70.3, and 44.9 % in the exposure group and 97.8, 81.4, and 53.1 % in the control group (p = 0.094).

Conclusions

Hepatectomy with exposure of tumor surface is technically demanding, but can be performed safely. It is also associated with a risk of tumor recurrence. Multidisciplinary combined therapy would be the solution and can contribute to improve overall survival.     

Feasibility of Laparoscopic Re-resection for Patients with Recurrent Hepatocellular Carcinoma

Background

Repeated resection via an open approach is an effective treatment for post-operative recurrent hepatocellular carcinoma (HCC). However, there are limited data on the application of laparoscopic approach for recurrent HCC in patients with prior liver resections. The aim of this study was to review our experience of laparoscopic re-resection in patients with postoperative tumor recurrence.

Materials and methods

A total of 11 patients received laparoscopic re-resections for postoperative tumor recurrence in our center. Data were reviewed for demographics, tumor characteristics, and perioperative outcomes. Case-match analysis with the open approach was performed in a 1:2 ratio.

Results

Six patients had their first liver resection carried out via the open approach and the remaining five patients received the laparoscopic approach. The recurrent tumor size was 20 mm (12–50 mm) and ten patients had a solitary recurrence. Two patients had laparoscopic left lateral sectionectomy and the remaining nine patients had sub-segmentectomies. There was no significant difference in patient characteristics, preoperative liver function, and tumor features between the laparoscopic and open groups. Perioperative blood loss was significantly reduced in the laparoscopic group (100 vs. 314 mL; p = 0.014) but the morbidity rate (18.2 vs. 4.5 %; p = 0.199) and length of hospitalization were comparable (6 vs. 5 days; p = 0.831). The 3-year overall survival rates for the laparoscopic and open groups were 60.0 and 89.3 %, respectively (p = 0.279).

Conclusion

Our study showed that laparoscopic re-resection for recurrent HCC was feasible with satisfactory postoperative and oncological outcomes, even in patients with previous major liver resections.     

Liver Transplantation in Patients with Hepatitis B Virus-Related Hepatocellular Carcinoma: The Influence of Viral Characteristics on Clinical Outcome

Background

Hepatitis B virus (HBV) relapse and/or hepatocellular carcinoma (HCC) recurrence remains a major concern for patients who undergo liver transplantation (LT) because of HBV-related HCC. This study investigates the correlation between HBV relapse and HCC recurrence and it explores factors that affect patient outcomes after LT.

Methods

Between September 2002 and August 2009, 78 consecutive patients who underwent LT because of HBV-related HCC were enrolled in this study. Serum samples obtained before LT were assayed both for virological factors associated with HBV DNA and for genotypic characteristics of the virus. All patient clinicopathological features and virological factors were assessed further by univariate and multivariate analyses to determine prognostic factors.

Results

During a median follow-up period of 29.4 months, 13 (16.6 %) patients experienced HCC recurrence and 18 (23.1 %) patients experienced HBV relapse. HBV relapse exhibited a close association with HCC recurrence (p = 0.004) and led to unfavorable overall survival after LT. Multivariate analysis of prognostic factors showed that the basal core promoter (BCP) mutation independently predicted a shorter survival period free from HBV relapse (p = 0.036). Moreover, with the exception of unfavorable tumor characteristics, the BCP mutation was found to be an important prognostic factor that affected HCC recurrence after LT (p = 0.042).

Conclusions

In this study, the HBV–BCP mutation was identified as an important predictor of post-LT clinical outcomes in patients with HBV-related HCC. Therefore, we recommend that aggressive antiviral treatment may be considered for patients associated with this risk factor.     

Analysis of the Risk Factors of Untransplantable Recurrence After Primary Curative Resection for Patients with Hepatocellular Carcinoma

Purpose

To determine the prognostic factors that predict recurrence of hepatocellular carcinoma (HCC) exceeding the University of California at San Francisco (UCSF) criteria after primary resection.

Methods

HCC patients who underwent curative liver resections between 2001 and 2007 and who were within the UCSF criteria (n = 716) were examined. Independent prognostic factors were examined by the Cox proportional hazard model.

Results

A total of 285 patients (39.8 %) developed recurrences. Of the patients who developed recurrences, 180 had HCC still within the UCSF criteria (63.2 %), and 105 developed HCC beyond this criteria (36.8 %). Among the population with primary transplantable HCC, patients with larger primary tumor sizes, serum α-fetoprotein (AFP) levels over 400 ng/mL, satellite nodules, vascular invasion, or undifferentiated HCC had a risk of untransplantable recurrence, as shown by univariate analysis. In multivariate analysis, undifferentiated HCC and vascular invasion were identified as the significant predictors with adjusted hazard ratios of 9.25 [95 % confidence interval (CI) 2.13–40.21] and 2.19 (95 % CI 1.34–3.58), respectively. When only preoperative factors were considered in multivariate analysis, primary tumor size and serum AFP levels over 400 ng/mL were identified as significant predictors with adjusted hazard ratios of 1.24 (95 % CI 1.07–1.45) and 1.72 (95 % CI 1.05–2.82), respectively.

Conclusions

For primary HCC patients within the UCSF criteria, larger tumor sizes and AFP levels over 400 ng/mL were associated with postresection recurrence of HCC exceeding the UCSF criteria. Because these are clearly markers for aggressive tumor biology, whether early primary transplant will alter the aggressive tumor behaviors warrant further investigation.     

Improved Diagnostic Imaging and Interventional Therapies Prolong Survival After Resection for Hepatocellular Carcinoma in Cirrhosis: The University of Bologna Experience Over 10 Years

Background

With substantial improvements in perioperative care and surgical technique, both mortality and morbidity after liver resection have progressively decreased; however, long-term prognosis is greatly affected by tumor recurrence, which represents the most frequent cause of death. The aim of this study is to analyze the outcome after hepatic resection in the present clinical scenario, where great improvements in diagnostic techniques, surveillance schedules, in other active treatments will potentially have a positive impact on survival.

Methods

Data from 300 consecutive hepatic resections performed on cirrhotic patients in a tertiary-care referral hospital from 1997 and 2008 were reviewed, and survival was calculated for the two periods considered. The first group of patients underwent hepatectomy between 1997 and 2002 (n = 126) and the second group of patients between 2003 and 2008 (n = 174).

Results

In the more recent period, tumor selection criteria for resectability included more patients with multinodular tumors so that solitary tumors decreased from 89.7 to 78.7% (P = 0.019); however, the tumor, node, metastasis (TNM) system stage remained unaffected. The 5-year recurrence rate remained similar (67.4 vs. 65.8%; P = 0.836). Despite these features, the 5-year patient survival increased from 52.6 to 65.8% (P = 0.023). This end result was related to a larger proportion of patients with tumor recurrence undergoing repeat resection or salvage transplantation that increased from 22.2 to 36.9% (P = 0.039).

Conclusions

The increased survival is most likely the result of more stringent follow-up as well as increased accuracy in detecting recurrence at earlier stages, and consequently of more chances for potential cure when treating recurrent tumor.     

Predictor for Histological Microvascular Invasion of Hepatocellular Carcinoma: A Lesson from 229 Consecutive Cases of Curative Liver Resection

Background

Microscopic vascular invasion is an important risk factor for recurrent hepatocellular carcinoma (HCC), even after curative liver resection or orthotopic liver transplantation. To predict microscopic portal venous invasion, the following two questions were examined retrospectively: Is it possible to detect microvascular invasion preoperatively? What are the characteristics of a group of early HCC recurrences even with no microvascular invasion?

Methods

Study 1 included 229 patients with HCC who underwent curative liver resection between 1991 and 2008; 127 had HCC without microscopic portal venous invasion, and 52 had HCC with microscopic portal venous invasion (MPVI). These two distinct groups were analyzed with regard to various clinicopathologic factors. Subsequently, we specifically investigated if HCCs <5 cm with vascular invasion (n = 32) have some characteristics that would allow detection of latent microvascular invasion. Study 2 included 127 HCC patients without MVPI; 42 had a recurrence within 2 years, and 85 patients were recurrence-free for at least 2 years. These two distinct groups were analyzed with regard to various clinicopathologic factors.

Results

HCC diameter of >5 cm, the macroscopic appearance of HCC, and high levels of preoperative des-γ-carboxyprothrombin are significant prognostic factors in identifying microvascular invasion of HCC. The strongest predictor of early recurrence (within 2 years) was the serum α-fetoprotein level in patients without clear microvascular invasion.

Conclusions

Tumor size, macroscopic appearance, and high tumor marker levels are important elements in identifying the group of patients with a low HCC recurrence rate after curative liver resection.