Assessment of ISGLS Definition of Posthepatectomy Liver Failure and Its Effect on Outcome in Patients with Hepatocellular Carcinoma

Background

Posthepatectomy liver failure (PHLF) is a major complication after hepatectomy. As there was no standardized definition, the International Study Group of Liver Surgery (ISGLS) defined PHLF as increased international normalized ratio and hyperbilirubinemia on or after postoperative day 5 in 2010. We evaluated the impact of the ISGLS definition of PHLF on hepatocellular carcinoma (HCC) patients.

Methods

We retrospectively analyzed 210 consecutive HCC patients who underwent curative hepatectomy at our facility from 2005 to 2010. The median follow-up period after hepatectomy was 35.2 months.

Results

Thirty-nine (18.6 %) patients fulfilled the ISGLS definition of PHLF. Overall survival (OS) rates at 1, 3, and 5 years in patients with/without PHLF were 69.1/93.5, 45.1/72.5, and 45.1/57.8 %, respectively (P?=?0.002). Recurrence-free survival (RFS) rates at 1, 3, and 5 years in patients with/without PHLF were 40.9/65.9, 15.7/38.3, and 15.7/20.3 %, respectively (P?=?0.003). Multivariate analysis revealed that PHLF was significantly associated with both OS (P?=?0.047) and RFS (P?=?0.019). Extent of resection (P?<?0.001), intraoperative blood loss (P?=?0.002), and fibrosis stage (P?=?0.040) were identified as independent risk factors for developing PHLF.

Conclusion

The ISGLS definition of PHLF was associated with OS and RFS in HCC patients, and long-term survival will be improved by reducing the incidence of PHLF.     

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.     

Volume–Outcome Associations after Major Hepatectomy for Hepatocellular Carcinoma: a Nationwide Taiwan Study

Objective

The objective of this study was to explore volume–outcome associations after major hepatectomy for hepatocellular carcinoma (HCC).

Methods

This population-based cohort study retrospectively analyzed 23,107 major hepatectomies for HCC patients from 1998 to 2009. Relationships between hospital/surgeon volume and patient outcome were analyzed by propensity score matching (PSM). Five-year overall survival (OS) was estimated by Kaplan–Meier method, and differences were compared by log-rank test.

Results

The mean length of stay (LOS) after major hepatectomy was 18.1 days, and the mean hospital cost was US$5,088.2. After PSM, the mean OS in high- and low-volume hospitals was 71.1 months (standard deviation (SD) 0.7 months) and 68.6 months (SD 0.6 months), respectively; the mean OS in high- and low-volume surgeons was 78.5 months (SD 0.7 months) and 66.9 months (SD 0.7 months), respectively. The PSM analysis showed that treatment by high-volume hospitals and treatment by high-volume surgeons were both associated with significantly shorter LOS, lower hospital cost, and longer survival compared to their low-volume counterparts (P?<?0.001).

Conclusions

The results of this nationwide study support the regionalization of HCC treatment by hospital volume and by surgeon volume. High surgeon volume revealed both short- and long-term benefits. The applicability of PSM in volume–outcome analysis may also be confirmed.     

Response to Preoperative Chemotherapy Predicts Survival in Patients Undergoing Hepatectomy for Liver Metastases from Gastric and Esophageal Cancer

Background

The role of hepatectomy for patients with liver metastases from gastric and esophageal cancer (GELM) is not well defined. The present study examined the morbidity, mortality, and long-term survivals after liver resection for GELM.

Methods

Clinicopathological data of patients who underwent hepatectomy for GELM between 1995 and 2012 at two European high-volume hepatobiliary centers were assessed, and predictors of overall survival (OS) were identified. In addition, the impact of preoperative chemotherapy for GELM on OS was evaluated.

Results

Forty-seven patients underwent hepatectomy for GELM. The primary tumor was located in the stomach, cardia, and distal esophagus in 27, 16, and 4 cases, respectively. Twenty patients received preoperative chemotherapy before hepatectomy. After a median follow-up time of 76 months, 1-, 3-, and 5-year OS rates were 70, 37, and 24 %, respectively. Postoperative morbidity and mortality rates were 32 and 4 %, respectively. Outcomes were comparable between the two centers. Preoperative chemotherapy for GELM (5-year OS: 45 vs 9 %, P?=?.005) and the lack of posthepatectomy complications (5-year OS: 34 vs 0 %, P?P?=?.045).

Conclusion

For selected patients with GELM, liver resection is safe and should be regarded as a potentially curative approach. A multimodal treatment strategy including systemic therapy may provide better patient selection resulting in prolonged survival in patients with GELM undergoing hepatectomy.     

Hepatectomy based on the tumor hemodynamics for hepatocellular carcinoma: a comparison among the hybrid and pure laparoscopic procedures and open surgery

Purpose

This study was designed to evaluate the surgical parameters and treatment outcomes of tumor hemodynamics-based pure laparoscopic (PURE) and laparoscopy-assisted (HYBRID) hepatectomy for small hepatocellular carcinoma (HCC) compared with those of open hepatectomy.

Methods

Using a prospectively collected database from 1997 to 2011, we analyzed the data of 56 consecutive cases of laparoscopic hepatectomy for HCC (PURE, n = 24; HYBRID, n = 29; HALS, n = 3) from among 102 cases undergoing laparoscopic hepatectomy. We employed 27 cases treated by open hepatectomy during the same period as controls.

Results

PURE was associated with lesser blood loss, lower weight of the resected liver, and a shorter skin incision than HYBRID and open hepatectomy [median blood loss (mL): PURE 7, HYBRID 380, Open 450; P < 0.05]. On the other hand, HYBRID hepatectomy was associated with a longer operation time [operation time (min): HYBRID 232, Open 185; P = 0.0226]. The length of hospitalization in the cases treated by PURE and HYBRID hepatectomy was shorter than that in the cases treated by open hepatectomy [length of hospitalization (days): PURE 11, HYBRID 12, Open 17; P < 0.05]. One case each of transfusion and morbidity was recorded in this series. There was no significant difference of the overall (OS) or disease-free survival (DFS) between the patients treated by laparoscopic and open hepatectomy (3-year OS: 100 vs. 100 %; DFS 50 vs. 62 %, respectively).

Conclusions

Neither the surgical parameters nor the treatment outcomes of hemodynamics-based laparoscopic hepatectomy were inferior to those of open hepatectomy.     

Treatment Strategy to Improve Long-Term Survival for Hepatocellular Carcinoma Smaller than 5 cm: Major Hepatectomy vs Minor Hepatectomy

Background

The extent of hepatectomy for solitary hepatocellular carcinoma (HCC) <5 cm is controversial.

Methods

This is a retrospective review of patients with solitary HCC <5 cm, who underwent liver resection in a tertiary referral centre in Hong Kong between January 1989 and December 2009. Baseline demographics, liver function, peri-operative outcomes, and overall survival were compared.

Results

A total of 348 cirrhotic patients with a solitary HCC <5 cm underwent either major hepatectomy (n = 93) or minor hepatectomy (n = 255). Child-Pugh status did not differ, 98.9 vs. 96.1 % (p = 0.319); all patients who underwent major and minor hepatectomy were classified as Child-Pugh status A. Patients who underwent major hepatectomy had a larger median tumor size (4.0 vs. 2.5 cm, p < 0.001) and they also had more advanced stage of disease (stage I/II/IIIa: 10.8/55.9/33.3 vs. 26.7/52.9/20.4 %, p = 0.002). Median operative time for major hepatectomy was significantly longer (415 vs. 248 min, p < 0.001) and entailed greater blood loss (0.9 vs. 0.5 l, p < 0.001). Despite larger tumor size and more advanced stage of disease in the major hepatectomy group, hospital mortality (5.4 vs. 2.0 %, p = 0.185), complication rates (30.1 vs. 23.1 %, p = 0.234), and transfusion rate (10.8 vs. 11.4 %, p = 0.862) were the same between the two groups. Overall survival was significantly better for those who underwent major hepatectomy, with a median survival of 147.5 vs. 92.1 months (p = 0.043), and they had a better 5- and 10-year disease-free survival rate (57.3 vs. 40.2, 38.1 vs. 18.9 %, p = 0.003). In subgroup analysis, the 10-year survival for patients with stage II HCC and tumor <5 cm was 68.6 vs. 36.6 % in those who received minor hepatectomy alone (p = 0.027).

Conclusions

Major hepatectomy provided better long-term survival benefit in patients with HCC <5 cm, particularly in those with stage II disease.     

New macroscopic classification and back-flow thrombectomy for advanced hepatocellular carcinoma with portal vein tumor thrombus invading the contralateral second portal branch

Purpose

Patients with hepatocellular carcinoma (HCC) and portal vein tumor thrombus (PVTT) invading the portal trunk (Vp4) are poor surgical candidates because of the technical difficulties involved. To overcome the limitations, we developed a technique of back-flow thrombectomy (BFT) based on the inherent portal hemodynamics and the macroscopic form of PVTT.

Methods

Forty-six patients with multiple HCC and Vp4 PVTT underwent hepatectomy with tumor thrombectomy. We used the BFT to treat 24 patients, 18 of whom had PVTT in the contralateral second portal branch. The form of PVTT was classified macroscopically into the floating and expansive types.

Results

The rate of complete removal by BFT of PVTT in the contralateral second portal branch was 89%. The patency rates at the thrombectomy site in all 46 patients and in the 24 BFT patients, 3 months after hepatectomy were 93 and 90%, respectively. The median OS of all 46 patients was 15 months, with 1- and 3-year OS rates of 58.5 and 17.1%, respectively. The median OS of the 24 patients treated with BFT vs. the 22 not treated with BFT was 14 and 15 months, respectively.

Conclusions

BFT can expand the therapeutic time window for patients with HCC and deep-seated PVTT and may improve their survival.

     

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.     

High Survival in Patients Operated for Small Isolated Liver Metastases from Gastric Cancer: A Multi-institutional Study

Background

Although several studies have reported the outcomes of surgery for the treatment of liver metastases of gastric cancer (GLM), indications for liver resection for gastric metastases remain controversial. This study was designed to identify prognostic determinants that identify operable hepatic metastases from gastric cancer and to evaluate the actual targets of surgical therapy.

Methods

Retrospective analysis was performed on outcomes for 24 consecutive patients at five institutions who underwent gastrectomy for gastric cancer followed by curative hepatectomy for GLM between 2000 and June 2012.

Results

Overall 5-year survival and median survival were 40.1 % and 22.3 months, respectively. Uni- and multivariate analyses showed that liver metastatic tumour size less than 5 cm was the most important predictor of overall survival (OS, p = 0.03). Four patients survived >5 years. Repeat hepatectomy was performed in three patients. Two of these patients have remained disease-free since the repeat hepatectomy.

Conclusions

GLM patients with metastatic tumour diameter less than 5 cm maximum are the best candidates for hepatectomy. Hepatic resection should be considered as an option for gastric cancer patients with liver metastases.     

Prognosis After Resection of Hepatitis B Virus-Related Hepatocellular Carcinoma Originating from Non-cirrhotic Liver

Background

Long-term prognosis after resection of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) originating from non-cirrhotic liver is not fully clarified.

Methods

A total of 183 patients who underwent curative hepatectomy for HCC without cirrhosis were classified into two groups: HBV infection group (n = 124) and non-HBV infection group (n = 59). Long-term postoperative outcomes were compared between the two groups.

Results

The 5-year postoperative overall survival (OS) and disease-free survival (DFS) were 42.6 and 39.0 %, respectively, in the HBV infection group versus 52.3 and 46.5 % in the non-HBV infection group (both p > 0.05). When patients were subdivided according to TNM stages, OS in stages II or III HCC patients was similar between the two groups. In contrast, OS and DFS were significantly worse in stage I patients with HBV infection than those in stage I patients without HBV infection (p = 0.041 and 0.038, respectively). Preoperative serum HBV DNA >4 log₁₀ copies/mL and vascular invasion were independent factors associated with poor prognosis (p = 0.034 and 0.017, respectively) for patients with HBV infection.

Conclusions

After hepatic resection for HCC in non-cirrhotic liver, patients with HBV infection with early-stage tumors had worse prognosis than patients without HBV infection, possibly due to the carcinogenetic potential of viral hepatitis in the remnant liver. Antiviral therapy should be considered after hepatectomy in patients with high HBV DNA levels.     

Role of Operative Therapy in Non-cirrhotic Patients with Metastatic Hepatocellular Carcinoma

Introduction

We investigated the role of operative therapy in non-cirrhotic patients who developed metastatic hepatocellular carcinoma (HCC).

Methods

This retrospective cohort study included consecutive non-cirrhotic patients with metastatic HCC after a prior hepatectomy treated between 1990 and 2009. Patients were stratified by operative therapy (resection, ablation, transcatheter therapy). Kaplan?CMeier analyses with log-rank comparisons tested effects of operative therapy on overall survival (OS) and progression-free survival (PFS).

Results

Of 195 non-cirrhotic patients treated for HCC during the study period, 98 [median age 65, interquartile range (IQR) 53?C71; 55?% male] subsequently developed metastatic HCC (55 intrahepatic only). Median time to development of metastases after the index operation was 10?months (IQR 5?C20?months); median number of metastases was 3 (IQR 2?C7). Half of these patients (n?=?50) underwent operative treatment of metastases; 20 (40?%) underwent metastasectomy, 18 (36?%) ablation, and 12 (24?%) transcatheter therapy. Operative therapy was associated with improved OS (p?p????0.006). Nine patients (seven resection, two ablation) are disease free at a median of 50?months (IQR 24?C80?months) posttreatment.

Conclusions

Resection and ablation are associated with an improved PFS and long-term OS and should be considered in select patients with metastatic 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.     

Number of Nodules,Child-Pugh Status,Margin Positivity,and Microvascular Invasion,but not Tumor Size,are Prognostic Factors of Survival after Liver Resection for Multifocal Hepatocellular Carcinoma

Background

Presently, the role of liver resection (LR) for multifocal hepatocellular carcinoma (HCC) remains controversial. However, in many regions worldwide, LR remains the only treatment modality available to such patients which offers the possibility of long-term cure. The aim of this study is to determine the outcomes and prognostic factors of patients with multifocal HCC after LR.

Methods

This is a retrospective analysis of 110 patients who underwent potentially curative LR for pathologically proven multifocal HCC between 2000 and 2011.

Results

The median age was 64 (range, 18–84)?years, and there were 88 males (80.0 %). Sixty-one patients underwent a major hepatectomy, and the overall postoperative mortality was 1.8 %. Sixty-eight patients had liver cirrhosis, of which, 58 were child’s A and 10 were child’s B. The 1- and 5-year overall survival (OS) was 82 and 44 %, respectively. The corresponding 1- and 5-year recurrence-free survival (RFS) was 57 and 19 %, respectively. Multivariate analysis demonstrated that the number of nodules (>3) and presence of microvascular invasion were associated with RFS. Number of nodules (>3), margin positivity, Child-Pugh status, and presence of microvascular invasion were independent prognostic factors of OS.

Conclusions

LR followed by treatment of recurrences may result in reasonable long-term survival and should be considered in a selected group of patients with multifocal HCC. Number of nodules (>3), margin positivity, Child-Pugh status, and presence of microvascular invasion, but not tumor size, were independent negative predictors of OS. These findings have potential implications on the AJCC staging for multifocal HCC.     

Adjuvant Hepatic Intra-arterial Iodine-131-Lipiodol Following Curative Resection of Hepatocellular Carcinoma: A Prospective Randomized Trial

Background

The purpose of the present study was to determine whether intrahepatic injection of ¹³¹I-lipiodol (Lipiodol) is effective against recurrence of surgically resected hepatocellular carcinoma (HCC).

Methods

From June 2001 through March 2007, this nationwide multi-center prospective randomized controlled trial enrolled 103 patients 4–6 weeks after curative resection of HCC with complete recovery (52: Lipiodol, 51: Control). Follow-up was every 3 months for 1 year, then every 6 months. Primary and secondary endpoints were recurrence-free survival (RFS) and overall survival (OS), respectively, both of which were evaluated by the Kaplan–Meier technique and summarized by the hazard ratio (HR). The design was based on information obtained from a similar trial that had been conducted in Hong Kong.

Results

The Lipiodol group showed a small, and nonsignificant, improvement over control in RFS (HR = 0.75; 95 % confidence interval [95 % CI] 0.46–1.23; p = 0.25) and OS (HR = 0.88; 95 % CI 0.51–1.51; p = 0.64). Only two serious adverse events were reported, both with hypothyroidism caused by ¹³¹I-lipiodol and hepatic artery dissection during angiography.

Conclusions

The randomized trial provides insufficient evidence to recommend the routine use of ¹³¹I-lipiodol in these patients.     

A Systematic Review of the Predictive Value of 18FDG-PET in Esophageal and Esophagogastric Junction Cancer After Neoadjuvant Chemoradiation on the Survival Outcome Stratification

Purpose

We studied the predictive value of [¹⁸?F]fluorodeoxyglucose-positron emission tomography (¹⁸FDG-PET) for assessing disease-free (DFS) and overall survival (OS) in esophageal and esophagogastric junction cancer.

Materials and methods

A literature search (PUBMED/MEDLINE, EMBASE, Cochrane) was performed to identify full papers with ¹⁸FDG-PET and survival data, using indexing terms and free text words. Studies with >10 patients with locally advanced esophageal cancer, presenting sequential or at least one post-adjuvant treatment ¹⁸FDG-PET data and Kaplan–Meier survival curves with >6 months median follow-up period were included. We performed a meta-analysis for DFS and OS using the hazard ratio (HRs) as outcome measure. Sources of heterogeneity study were also explored.

Results

We identified 26 eligible studies including a total of 1,544 patients (average age 62 years, 82 % males). The TNM distribution was as follows: stage I 7 %, II 24 %, III 53 % and IV 15 %. The pooled HRs for complete metabolic response versus no response were 0.51 for OS (95 % CI, 0.4–0.64; P?<?0.00001) and 0.47 for DFS (95 % CI, 0.38–0.57; P?<?0.00001), respectively. No statistical heterogeneity was present. To explore sources of clinical heterogeneity, we also realised subgroup and regression analyses. Taken into account the moderate correlation between OS and DFS (ρ?=?0.54), we used joint bivariate random regression model. These analyses did not show a statistically significant impact of study characteristics and PET modalities on the pooled outcome estimates.

Conclusion

Despite methodological and clinical heterogeneity, metabolic response on ¹⁸FDG-PET is a significant predictor of long-term survival data.     

Adjuvant Hepatic Arterial Infusion Chemotherapy after Hepatic Resection of Hepatocellular Carcinoma With Macroscopic Vascular Invasion

Background

The prognosis of hepatocellular carcinoma (HCC) with macroscopic vascular invasion is extremely poor even after hepatic resection. We aimed to clarify the efficacy of adjuvant hepatic arterial infusion chemotherapy (HAI) for HCC with vascular invasion.

Methods

A total of 73 HCC patients with macroscopic vascular invasion were divided into two groups: 38 with hepatectomy with HAI (HAI group) and 35 with hepatectomy alone (non-HAI group). From 1997 to 2007, HAI was performed via an implanted injection port. The treatment comprised three courses of weekly infusion of HAI, which comprised cisplatin (10 mg daily on days 1–5) followed by 5-fluorouracil (5-FU; 250 mg daily on days 1–5) infusion. From 2007, cisplatin (60 mg/m²), 5-FU (600 mg/m²), and a mixture of mitomycin C (3 mg/m²) and degradable starch microspheres were administered for two courses.

Results

Overall, 92 % of patients completed adjuvant HAI. In the HAI and non-HAI groups, the 5-year disease-free survival (DFS) rates were 33.1 % and 11.8 %, respectively (p = 0.029), and the 5-year overall survival (OS) rates were 46.7 % and 32.7 %, respectively (p = 0.318). Among the patients with Vp3/4 or Vv3 (n = 32) in the HAI group, the 3-year DFS and OS rates were 33.7 % and 56.8 %, respectively (p = 0.049). Those in the non-HAI group were 8.3 % and 12.0 %, respectively (p = 0.023). Cox proportional multivariate analysis for DFS revealed that HAI was an independent favorable prognostic factor in all 73 patients (hazard ratio 0.536; p = 0.029).

Conclusions

Adjuvant HAI for HCC patients with vascular invasion might reduce the risk of recurrence.     

Survival Benefit of Surgical Treatment for Hepatocellular Carcinoma with Inferior Vena Cava/Right Atrium Tumor Thrombus: Results of a Retrospective Cohort Study

Background

The significance of surgery in the treatment of hepatocellular carcinoma (HCC) extending into the inferior vena cava (IVC)/right atrium (RA) is currently unclear. We sought to clarify whether surgical treatment can improve survival in such patients.

Methods

A retrospective review was undertaken of patients with HCC and IVC/RA tumor thrombus who were potential candidates for surgery but who were finally treated surgically and nonsurgically between September 2000 and October 2010. The patients were subdivided according to therapeutic modalities, and the results for each group were compared.

Results

A total of 56 patients were included in this study. They were divided into three groups. Twenty-five patients underwent hepatectomy plus thrombectomy (surgical group), with minor morbidity and no mortality; the patients in this group had 1-, 3-, and 5-year survival rates of 68.0, 22.5, and 13.5 %, respectively, with a median survival of 19 months. Twenty patients were treated with transcatheter arterial chemoembolization, with 1- and 3-year survival rates of 15.0 and 5.0 %, respectively (median survival 4.5 months). Eleven patients received symptomatic treatment only, and no one in this group survived longer than 1 year (median survival 5 months). The patients in surgical group survived significantly longer than the patients in the other two groups (p < 0.001).

Conclusions

Although technically challenging, surgery for HCC with IVC/RA tumor thrombus can be safely performed and should be considered in patients with resectable primary tumor and sufficient hepatic reservoir because compared with transcatheter arterial chemoembolization or symptomatic treatment, it significantly improved patient survival.     

Unresectable Colorectal Liver Metastases: The Safety and Efficacy of Conversion Therapy Using Hepatic Arterial Infusion Immunochemotherapy with 5-Fluorouracil and Polyethylene Glycol-Interferon α-2a

Background

Hepatic arterial infusion (HAI) or systemic chemotherapy has been used to treat unresectable colorectal liver metastases. The prognosis of the disease in recent years has been improved because chemotherapy is performed before hepatectomy to reduce tumor size (conversion therapy). The purpose of this study was to investigate the safety and efficacy of conversion therapy following HAI immunochemotherapy.

Methods

Hepatic arterial infusion of 5-fluorouracil (5-FU)/polyethylene glycol (PEG)-IFNα-2a was performed in 21 patients. The primary endpoint was the safety of HAI and hepatectomy. The secondary endpoints were response rate, rate of conversion to hepatectomy, survival rate, and prognostic factors.

Results

With regard to side effects, drugs were discontinued temporarily in one patient because of a decrease in white blood cell count; however, other patients continued chemotherapy. The response rate with HAI was 61.9 %, and the conversion rate was 38.1 %. Hepatectomy was completed successfully without mortality. Median progression-free survival (PFS) was 11.5 months (with and without conversion, 16.7 and 4.8 months, respectively; p = 0.021). Median overall survival was 34.6 months (with and without conversion, 48.4 and 26.6 months, respectively; p = 0.003). Prognosis was poor when the number of metastatic tumors was ≥10 [PFS: hazard ratio (HR) 32.21, p = 0.003; overall survival (OS): HR 9.13, p = 0.07], but prognosis improved after hepatectomy (OS: HR 0.08, p = 0.09).

Conclusions

Hepatic arterial infusion immunochemotherapy with 5-FU/PEG-IFNα-2a was performed safely without major side effects. Prognosis is expected to improve after successful conversion to hepatectomy.     

Predictors for Early Recurrence After Hepatectomy for Initially Unresectable Colorectal Liver Metastasis

Background

Early recurrence correlates with poor survival following various cancer surgeries and puts considerable stress on patients both physically and mentally. This retrospective study investigated the predictive factors for early recurrence after surgical resection for initially unresectable colorectal liver metastasis to elucidate indications for conversion strategies.

Methods

We retrospectively studied 46 patients who underwent hepatectomy after chemotherapy for initially unresectable colorectal liver metastasis from 1997 to 2010.

Results

Recurrences occurred within 6 months after hepatectomy in 13 patients (37 %). The median survival time of 21.2 months and the 5-year survival rate of 0 % after hepatectomy in patients with recurrence within 6 months were significantly worse than those in patients with recurrence more than 6 months after hepatectomy. Recurrence in less than 6 months was significantly correlated with impossibility of anticancer therapy for recurrence after hepatectomy (p?=?0.01). Eight or more hepatic tumors after chemotherapy were the only predictor of recurrence within 6 months (p?=?0.01; odds ratio 9.6; 95 % confidence interval 1.5–60.6).

Conclusion

Recurrence within 6 months was significantly correlated with a poorer outcome following surgery for initially unresectable colorectal liver metastasis. Surgical indication for initially unresectable colorectal liver metastasis with eight or more hepatic tumors after chemotherapy should be considered carefully in the light of mental and physical status, co-morbidity, and alternative treatment plans.     

Surgical Resection After Down-Staging of Locally Advanced Hepatocellular Carcinoma by Localized Concurrent Chemoradiotherapy

Background

This study evaluated the down-staging efficacy and impact on resectability of concurrent chemoradiotherapy (CCRT) followed by hepatic arterial infusion chemotherapy (HAIC) in locally advanced hepatocellular carcinoma, and identified prognostic factors of disease-free survival (DFS) and overall survival (OS) after curative resection.

Methods

DFS and OS were investigated using clinicopathologic variables. Functional residual liver volume (FRLV) was assessed before CCRT and again before surgery in patients with major hepatectomy. Tumor marker response was defined as elevated tumor marker levels at diagnosis but levels below cutoff values before surgery (α-fetoprotein < 20 ng/mL, protein induced by vitamin K absence or antagonist-II < 40 mAU/mL).

Results

Of 243 patients who received CCRT followed by HAIC between 2005 and 2011, 41 (16.9 %) underwent curative resection. Tumor down-staging was demonstrated in 32 (78 %) of the resected patients. FRLV significantly increased from 47.5 to 69.9 % before surgery in patients who underwent major hepatectomy. In addition, the OS of the curative resection group was significantly higher than the OS of the CCRT followed by HAIC alone group (49.6 vs. 9.8 % at 5-year survival; p < 0.001). By multivariate analysis, the poor prognostic factors for DFS after curative resection were tumor marker non-response and the presence of a satellite nodule; however, tumor marker non-response was the only independent poor prognostic factor of OS.

Conclusions

CCRT followed by HAIC increased resectability by down-staging tumors and increasing FRLV. Curative resection may provide good long-term survival in tumor marker responders who undergo CCRT followed by HAIC.