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Aim: Sorafenib was previously considered a first-line treatment for hepatocellular carcinoma (HCC) patients with macroscopic portal vein tumor thrombus (PVTT). This case-matched analysis was performed to evaluate the best first-line treatment for HCC in patients with macroscopic PVTT., Methods: The HCC patients with Vp2 (PVTT invaded into a second-order portal branch), Vp3 (first-order portal branch), and Vp4 (main trunk or contralateral portal vein) PVTT who underwent hepatectomy and those treated with sorafenib were included. Treatment results were compared between the two modalities for each PVTT category, and a propensity analysis was performed for patients with Vp3 and Vp4 (Vp3/4)., Results: The median survival times (MSTs) of patients with Vp2, Vp3, and Vp4 PVTT who underwent hepatectomy were 21.4, 13.6, and 14.9 months, respectively; the MSTs for those with Vp2, Vp3, and Vp4 PVTT who received sorafenib treatment were 6.9, 5.5, and 3.6 months, respectively, with a significant difference. In a propensity-matched cohort of patients with Vp3/4 PVTT (36 patients in each), the MST of patients who underwent hepatectomy (15.1 months) was significantly better than the patients treated with sorafenib (4.5 months)., Conclusion: Hepatectomy can be associated with prolonged survival in HCC patients with macroscopic PVTT., (© 2022 Japanese Society of Hepato-Biliary-Pancreatic Surgery.)

A 68-year-old woman underwent Miles' surgery with a diagnosis of a rectalgastrointestinalstromaltumor (GIST)in 2004. In 2005 and 2006, she developed liver metastases that were surgically removed, but once again in June 2006, she presented with liver metastasis, and imatinib therapy(400mg/day)was administered. In October 2016, she was diagnosed with progression of liver metastasis, and a tumor in the pancreatic body was identified on a CT scan. The patient was referred to our institution for treatment. We performed right hepatectomy and distalpancreatectomy in January 2017. Immunohistochemically, the recurrent tumor was positive for c-kit and CD34, and the diagnosis of GIST was confirmed. The pathological diagno- sis was a high-risk GIST showing 43mitoses per 50 high-power fields. Imatinib therapy(400mg/day)was administered after surgery. She is currently alive without recurrence.

Background and Aims: Small hypovascular hepatocellular carcinoma (HCC) ≤2 cm is biologically less aggressive than hypervascular one, however, the optimal treatment is still undetermined. The efficacy of surgical resection (SR), radiofrequency ablation (RFA) and percutaneous ethanol injection (PEI) was evaluated., Methods: The 853 (SR, 176; RFA, 491; PEI, 186) patients were enrolled who met Child-Pugh A/B, single hypovascular HCC ≤2 cm pathologically proven, available tumour differentiation and absence of macrovascular invasion and extrahepatic metastasis. Overall and recurrence-free survivals were compared in original and a propensity score weighted pseudo-population with 732 patients., Results: The median follow-up time and tumour size were 2.8 years and 1.47 cm respectively. In original population, multivariate Cox regression showed no significant difference for overall survival among three groups. In pseudo-population, Cox regression also revealed no significant difference for overall survival among them, although SR (HR, 0.56; 95% CI, 0.36-0.86) and RFA (HR, 0.75; 95% CI, 0.57-1.00) groups had significantly lower recurrence than PEI group. The overall survival rates at 3 and 5 years for the SR, RFA and PEI groups were 94%/70%, 90%/75% and 94%/73% respectively. Corresponding recurrence-free survival rates were 64%/54%, 59%/41% 48%/33% respectively. Subgroup analysis revealed no significant survival benefit of SR compared with non-SR. No treatment-related death occurred., Conclusions: For patients with single hypovascular HCC ≤2 cm, no significant difference for overall survival was first identified among 3 treatment groups. The SR or RFA could be recommended, and PEI would be alternative to RFA., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Two serology-based scoring models for prognostication of patients with hepatocellular carcinoma (HCC), the BALAD and BALAD-2 models, were applied to a Japanese cohort of a nationwide follow-up survey of HCC. The ability of these models to predict the progression of HCC and the deterioration of liver function and to assess prognosis was evaluated., Methods: BALAD and BALAD-2 scores were calculated in 24,029 patients from a cohort of Japanese nationwide survey based on the serum levels of five markers (bilirubin, albumin, lens culinaris agglutinin-reactive alpha-fetoprotein, alpha-fetoprotein, and des-gamma-carboxy prothrombin) measured at the time of HCC diagnosis. The associations of these scores with the progression of HCC and liver function and with survival rates were analyzed., Results: There were good correlations between BALAD and BALAD-2 scores and the progression of HCC and Child-Pugh class. Both scores accurately categorized patients into risk groups with different survival rates. BALAD-2 showed superior discrimination of patient survival compared with the original BALAD., Conclusions: Serology-based scoring models for prognostication, especially the BALAD-2 model, were useful for staging and prognostication of survival in a cohort of Japanese patients with HCC from a nationwide survey.

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.

Purpose: We assessed the predictive value of the preoperative neutrophil-to-lymphocyte ratio (NLR) in patients who underwent a two-stage treatment combining reductive surgery and percutaneous isolated hepatic perfusion for multiple hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT)., Methods: Forty-two patients underwent the two-stage treatment between January 2000 and December 2014 at Kobe University Hospital (Hyogo, Japan). The NLR was calculated from lymphocyte and neutrophil counts in the preoperative routine blood test. Clinical data and overall survival were compared statistically and multivariate analysis was done to identify prognostic factors., Results: The median survival of patients with a preoperative NLR > 2.3 was 14.9 months (n = 13), whereas that of patients with a preoperative NLR ≤ 2.3 was 26.1 months (n = 29; P = 0.022). A preoperative NLR > 2.3 was an independent prognostic factor in patients with multiple HCC with PVTT [hazard ratio (HR) 2.329; 95 % confidence interval (CI) 1.058-5.667; P = 0.036]., Conclusion: Based on the results of this study, an elevated preoperative NLR is an independent predictive risk factor for patients undergoing two-stage treatment for multiple HCC with PVTT.

Background: In the present study, we conducted a multicenter nationwide survey to investigate the effects of preoperative fluorine-18-fluorodeoxyglucose (FDG) positron emission tomography (PET) on the prediction of hepatocellular carcinoma (HCC) recurrence after liver transplantation (LT)., Methods: From 16 Japanese LT centers, data were collected on 182 recipients with HCC who underwent living donor liver transplantation (LDLT) between February 2005 and November 2013. PET-positive status was defined as increased uptake of FDG in the tumor compared to the surrounding non-tumor liver tissue. The median follow-up after LDLT was 54.5 months (range 1-125 months)., Results: Postoperative HCC recurrence occurred in 23 patients. Multivariate analysis revealed that exceeding the Milan criteria (MC), alpha-fetoprotein (AFP) level ≥115 ng/ml, and PET-positive status were significant and independent risk factors for recurrence. In the over-MC group, a subgroup of patients with AFP level <115 ng/ml and PET-negative status (n = 22) had a significantly lower 5-year recurrence rate than the other patients (n = 27, 19% vs. 53%, P = 0.019)., Conclusions: These results suggest that preoperative FDG-PET status offers additional information on HCC recurrence risk after LT. Over-MC patients with PET-negative status and lower AFP level may achieve successful outcome comparable to that of within-MC patients., (© 2016 Japanese Society of Hepato-Biliary-Pancreatic Surgery.)

Background & Aims: The presence of portal vein tumor thrombosis (PVTT) in patients with hepatocellular carcinoma (HCC) is regarded as indicating an advanced stage, and liver resection (LR) is not recommended. The aim of this study was to evaluate the survival benefit of LR for HCC patients with PVTT through the analysis of the data from a Japanese nationwide survey., Methods: We analyzed data for 6474 HCC patients with PVTT registered between 2000 and 2007. Of these patients, 2093 patients who underwent LR and 4381 patients who received other treatments were compared. The propensity scores were calculated and we successfully matched 1058 patients (66.1% of the LR group)., Results: In the Child-Pugh A patients, the median survival time (MST) in the LR group was 1.77years longer than that in the non-LR group (2.87years vs. 1.10years; p<0.001) and 0.88years longer than that in the non-LR group (2.45years vs. 1.57years; p<0.001) in a propensity score-matched cohort. A subgroup analysis revealed that LR provides a survival benefit regardless of age, etiology of HCC, tumor marker elevation, and tumor number. The survival benefit was not statistically significant only in patients with PVTT invading the main trunk or contralateral branch. In the LR group, the postoperative 90-day mortality rate was 3.7% (68 patients)., Conclusions: As long as the PVTT is limited to the first-order branch, LR is associated with a longer survival outcome than non-surgical treatment., Lay Summary: The presence of portal vein tumor thrombosis in patients with hepatocellular carcinoma is regarded as indicating an advanced stage, and liver resection is not recommended. We performed a multicenter, nationwide study to assess the survival benefit of liver resection in hepatocellular carcinoma patients with portal vein tumor thrombosis using propensity score-based matching. As long as the portal vein tumor thrombosis is limited to the first-order branch, liver resection is associated with a longer survival outcome than non-surgical treatment., (Copyright © 2016 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

This study aimed to evaluate the efficacy of stereotactic body radiotherapy (SBRT) compared with three-dimensional conformal radiotherapy (3DCRT). Forty-three patients with portal vein tumor thrombosis (PVTT)/inferior vena cava tumor thrombosis (IVCTT) treated with SBRT (27 with CyberKnife (CK) and 16 with TrueBeam (TB)) from April 2013 to December 2014, and 54 treated with 3DCRT from June 2008 to March 2013 were evaluated. Dosimetric parameters, response to radiotherapy (RT) and survival outcomes were compared in total SBRT vs. 3DCRT, CK vs. 3DCRT and TB vs. 3DCRT, respectively. The median biologically effective dose 10 (BED 10 ) values in total SBRT, CK, TB and 3DCRT were 73.4 Gy 10 , 75.0 Gy 10 , 60.5 Gy 10 and 58.5 Gy 10 , respectively (P < 0.001 in total SBRT vs. 3DCRT, P < 0.001 in CK vs. 3DCRT, P = 0.004 in TB vs. 3DCRT). The tumor response rates were 67%, 70%, 62% and 46%, respectively (P = 0.04, P = 0.04, P = 0.25). The 1-year overall survival rates were 49.3%, 56.7%, 38.1% and 29.3%, respectively (P = 0.02, P = 0.02, P = 0.30), and the 1-year local progression rates were 20.4%, 21.9%, 18.8% and 43.6%, respectively (P = 0.01, P = 0.04, P = 0.10). The use of SBRT made it possible to achieve a higher BED 10 compared with the use of 3DCRT. Improvements in local control and survival were achieved in the CK group and the total SBRT group. Our results suggest that SBRT may have the potential to be the standard RT technique for the treatment of PVTT/IVCTT., (© The Author 2016. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.)

We herein examined the immunohistochemical expression of 2 hepatocyte-specific transporters (bile salt export pump [BSEP] and multidrug-resistance protein 3 [MDR3]) in hepatocellular carcinomas (HCCs, n=54), intrahepatic cholangiocarcinomas (n=34), combined hepatocellular and cholangiocarcinomas (n=23), and hepatoid carcinomas originated from extrahepatic organs (n=27) to compare their diagnostic values with those of arginase-1 (ARG1) and hepatocyte paraffin-1 (HepPar-1). BSEP was expressed in 91% of HCCs and MDR3 in 83%. Although their sensitivities were slightly lower than those of ARG1 (96%) and HepPar-1 (93%), the 2 transporters appeared to be more specific for HCCs. ARG1 and HepPar-1 were expressed in intrahepatic cholangiocarcinomas (9% and 6%) and hepatoid carcinomas (22% and 44%, respectively), whereas BSEP and MDR3 were entirely negative in these neoplasms, except for 1 case of BSEP-positive hepatoid carcinoma of the esophagus. The highly specific expression of BSEP and MDR3 in hepatocytes was recapitulated in additional examinations of combined hepatocellular and cholangiocarcinomas, in which the expression of the transporters was restricted to morphologically hepatocellular areas. In contrast, ARG1 and HepPar-1 were also variably positive in areas of biliary or indeterminate differentiation. We also applied BSEP and MDR3 immunohistochemistry to 8 biopsy cases of poorly differentiated primary liver cancer, in which the original diagnosis was not conclusive. The diagnosis of HCC was retrospectively suggested in 2 cases expressing both BSEP and MDR3. In conclusion, given the highly specific expression of BSEP and MDR3 in HCCs, immunohistochemistry for these transporters will be useful not only for determining hepatocellular differentiation in primary liver cancers but also for discriminating HCCs from hepatoid carcinomas.

A 61-year-old woman was referred to our hospital for surgery for gallstones. She was diagnosed as having gallbladder cancer after a detailed radiologic examination. At the first laparotomy, gallbladder cancer with bulky invasion to the liver and multiple liver metastases were observed. Gemcitabine plus cisplatin (GC) administration was chosen. After 7 administration of GC, we changed GC to gemcitabine alone due to blood toxicity. After 7 months of chemotherapy, although CT findings showed regression of the liver invasion and the liver metastases, the serum CA19-9 level gradually increased. Because there were no obvious distant metastases on detailed radiologic examination, we performed surgery for the primary lesion after obtaining informed consent. Pathological examination demonstrated fibrosis without viable cancer cells in the metastatic liver tumor. Gemcitabine was administered as post-operative adjuvant chemotherapy. Twelve months after surgery, there was no sign of recurrence.

A 38-year-old man underwent right hepatectomy for a huge hepatocellular carcinoma(HCC)in the right hepatic lobe. Four months later, recurrent and metastatic disease were observed in the remnant liver and right lung, respectively. We performed a hepatectomy for the recurrent lesion because transcatheter arterial chemoembolization (TACE) was not effective. After surgery, we initiated sorafenib treatment for the lung metastases. One year later, the lung metastases worsened and metastases were observed in the mediastinal lymph nodes, and both metastatic lesions were resected. Seven months later, para-aortic lymph nodal metastasis was observed and dissected. Three months later, metastasis to the supraclavicular lymph node was observed. We performed particle radiation therapy and a complete response was achieved. One year later, metastases in both lungs were observed and resected. Despite continued sorafenib administration throughout the clinical course, a metastasis to the left adrenal gland was observed. This lesion was extirpated because no other recurrent lesions were detected. At 4 years and 6 months after the first operation, no other recurrences have occurred. Currently, sorafenib is the initial drug of choice for HCC with extrahepatic metastases. It is possible to improve the prognosis of patients with HCC and extrahepatic metastases by applying surgical treatment during the course of sorafenib administration.

Alpha-fetoprotein (AFP) and des-γ-carboxy prothrombin (DCP) are frequently used as tumor markers in hepatocellular carcinoma (HCC). The authors hypothesized different patient populations with varying tumor sizes would influence the predictive power of tumor markers for survival in HCC patients. The authors investigated the influence of tumor size on predictive powers of AFP and DCP. 181 patients underwent hepatectomy for HCC from 2003 to 2008 at Kobe University Hospital. Tumor markers were measured before and at 1 month post-hepatectomy. The Cox proportional-hazards model revealed that preoperative serum AFP was associated with survival; its effects depended on tumor size. Hazard ratios (HRs) for preoperative AFP were maximum for medium-sized HCC, and for DCP, HRs were maximum in small-sized tumors. Post-hepatectomy, both tumor markers were associated with survival, revealing significant interactions with tumor size. HRs for postoperative AFP were greater than 1 for relatively wide range tumors (3-11 cm). HRs for postoperative DCP increased with tumor size, with a strong prognostic predictive power for tumors >5 cm. The predictive power of serum tumor markers varied by tumor size in HCC patients. By selecting the appropriate tumor marker, its predictive power can be improved.

Objective: To compare the prognostic factors and outcomes after hepatic resection among patients with hepatitis B virus (HBV)-positive, hepatitis C virus (HCV)-positive, and negative for hepatitis B surface antigen and hepatitis C antibody, so-called "NBNC"-hepatocellular carcinoma (HCC) using the data from a nationwide survey., Background: The incidence of NBNC-HCC is rapidly increasing in Japan., Methods: A total of 11,950 patients with HBV-HCC (n = 2194), HCV-HCC (n = 7018), or NBNC-HCC (n = 2738) who underwent a curative hepatic resection were enrolled in this study. The clinicopathological features were compared among the groups. The significant prognostic variables determined by univariate analysis were subjected to a multivariate analysis using a Cox proportional hazard regression model., Results: Liver function in the HCV-HCC group was significantly worse than that in the HBV-HCC and NBNC-HCC groups. The NBNC-HCC group had significantly more advanced HCC than the HCV-HCC group. The 5-year overall survival rates after hepatectomy in the HBV-HCC, HCV-HCC, and NBNC-HCC groups were 65%, 59%, and 68%, respectively. The 5-year recurrence-free survival (RFS) rates in these 3 groups were 41%, 31%, and 47%, respectively. Stratifying the RFS rates according to the TNM stage showed that the NBNC-HCC group had a significantly better prognosis than the HBV-HCC group in stages II, III, and IVA, and a significantly better prognosis than the HCV-HCC group in stages I and II. Multivariate analysis revealed a significantly better RFS rate in the NBNC-HCC group., Conclusions: The findings of this nationwide survey indicated that patients with NBNC-HCC had a significantly lower risk of HCC recurrence than those with HBV-HCC and HCV-HCC.

Recently, the indications for particle beam therapy have been expanded to include metastatic liver tumors. However, its adverse effects on the treated liver are unclear, and the possibility of local recurrence after treatment should not be ignored. A 65-year-old man with advanced rectal carcinoma underwent low anterior resection. Resectable metastatic liver tumors were detected after adjuvant chemotherapy; however, he opted to undergo particle beam therapy. Nine months after treatment, a local recurrence was detected around the treated area, and central bisegmentectomy of the liver was performed as a salvage operation. The operation was technically complicated owing to severe adhesions and inflammatory changes in the liver parenchyma around the treated area. Pathological examination revealed advanced liver fibrosis at the treated area, in contrast with normal parenchyma in the untreated area. Although the procedure requires advanced surgical techniques, salvage surgery is a feasible option for recurrent liver tumors after particle beam therapy.

The patient was a 79-year-old man diagnosed with a single 9.3-cm hepatocellular carcinoma (HCC) in the medial segment of the liver, and left iliac bone metastasis. Initially, the patient was treated with a hepatic arterial infusion of low-dose FP (cisplatin/5-fluorouracil) at another hospital. Here, the patient received particle therapy for the left iliac bone metastasis at a total dose of 52.8 Gy in 4 fractions. Subsequently, he underwent medial segmentectomy of the liver to treat the primary HCC. Eleven months later, the first intrahepatic recurrence occurred, and the tumor was treated with percutaneous radiofrequency ablation (RFA). A second intrahepatic recurrence was detected 39 months later, which was also treated with percutaneous RFA. The patient remains well, with no evidence of tumor recurrence.

Hepatic epithelioid hemangioendothelioma (HEH) is a rare neoplasm of vascular origin with variable malignant potential. Because most patients with this condition have multiple bilobar lesions, liver transplantation is the standard treatment, and hepatectomy is much less frequently indicated. We describe a case of a 35-year-old woman with unresectable multiple bilobar HEH successfully treated by combination treatment with hepatectomy and carbon-ion radiotherapy. This case is very meaningful since it demonstrated the effectiveness of carbon-ion radiotherapy for HEH and the possibility of expanding the curative treatment options for multiple bilobar hepatic tumors.

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.

Objective: The aim of the present study was to investigate the background characteriscs of ruptured hepatocellular carcinoma (HCC) and to clarify the true impact of tumor rupture on patient prognosis in a large patient cohort., Background: Spontaneous tumor rupture of HCC has been associated with a very poor patient prognosis and the current TNM staging systems classify ruptured HCC as T4 based on insufficient evidence., Methods: In total, 1106 patients with ruptured HCC were extracted from the database of a nationwide survey conducted in Japan from 2000 to 2005. The clinicopathological parameters associated with HCC rupture were investigated using univariate and multivariate logistic regression models. The survival curves for ruptured and nonruptured HCC were generated and compared to evaluate the impact of the event (rupture) itself on patient prognosis and the TNM staging systems., Results: The multivariate analyses showed that tumor rupture was associated with both a poor liver functional reserve and an advanced tumor status. Analyses of the survival curves stratified according to the baseline TNM staging showed that tumor rupture had an additional impact on the baseline survival curves without rupture, and the impact corresponded to the addition of 0.5 to 2 stages to the baseline tumor staging., Conclusions: The present study suggested that tumor rupture itself had a negative impact on patient survival. However, its impact was not strong enough to cancel the effects of the other tumor-related parameters. Therefore, it may be appropriate to give additional stages to the baseline tumor staging in cases of ruptured HCC.

Background: Sorafenib is currently recommended as first-line therapy for patients with intermediate or advanced hepatocellular carcinoma (HCC) per Barcelona Clinic Liver Cancer staging. However, the median overall survival (OS) with sorafenib in these patients is 10.7 months with an overall response rate of 2 %. We retrospectively investigated the long-term outcomes and prognostic factors with reductive hepatectomy and sequential percutaneous isolated hepatic perfusion (PIHP) for refractory intermediate or advanced HCC., Methods: A total of 68 patients who had intermediate or advanced stage HCC without extrahepatic metastases were scheduled for reductive hepatectomy plus PIHP. All patients underwent reductive hepatectomy and PIHP with mitomycin C 20-40 mg/m(2) and/or doxorubicin 60-120 mg/m(2) 1-3 months after surgery (mean, 1.51 times/patient)., Results: The objective response rate of PIHP was 70.6 % (complete plus partial response). The median OS of all 68 patients was 25 months, and the 5-year OS rate was 27.6 %. Univariate and multivariate analyses indicated that tumor response to PIHP and normalization of serum des-γ-carboxy prothrombin concentrations after PIHP were independent prognostic factors for OS., Conclusions: The median OS of the study population treated by reductive hepatectomy and sequential PIHP was 25 months. This treatment strategy can offer a possible curative treatment to patients with refractory intermediate and advanced HCC.

Objective: To examine the prognostic factors and outcomes after several types of treatments in patients with hepatocellular carcinoma (HCC) negative for hepatitis B surface antigen and hepatitis C antibody, so-called "non-B non-C HCC" using the data of a nationwide survey., Background: The proportion of non-B non-C HCC is rapidly increasing in Japan., Methods: A total of 4741 patients with non-B non-C HCC, who underwent hepatic resection (HR, n = 2872), radiofrequency ablation (RFA, n = 432), and transcatheter arterial chemoembolization (TACE, n = 1437) as the initial treatment, were enrolled in this study. The exclusion criteria included extrahepatic metastases and/or Child-Pugh C. Significant prognostic variables determined by a univariate analysis were subjected to a multivariate analysis using a Cox proportional hazard regression model., Results: The degree of liver damage in the HR group was significantly lower than that in the RFA and TACE groups. The HR and TACE groups had significantly more advanced HCC than the RFA group. The 5-year survival rates after HR, RFA, and TACE were 66%, 49%, and 32%, respectively. Stratifying the survival rates, according to the TNM stage and the Japan Integrated Staging (JIS) score, showed the HR group to have a significantly better prognosis than the RFA group in the stage II and in the JIS scores "1" and "2." The multivariate analysis showed 12 independent prognostic factors. HR offers significant prognostic advantages over TACE and RFA., Conclusions: The findings of this large prospective cohort study indicated that HR may be recommended, especially in patients with TNM stage II and JIS scores "1" and "2" of non-B non-C HCC.

Objective: To clarify the clinical significance of resection of lymph node metastases in patients' hepatocellular carcinoma (HCC)., Background: Although the presence of lymph node metastasis form HCC has been considered as a systemic disease, prognosis after resection of them remains unknown., Methods: From the database of a Japanese nationwide survey, 14,872 patients of HCC treated by surgical resection between 2000 and 2005 were enrolled. We modified the current Japanese staging system for HCC, by further dividing stage IVA into stage IVAnon-n1 and stage n1, according to the absence or presence of pathologically proven lymph node metastasis. Thus, the patients classified into 6 disease stages, that is, I (n=1494), II (n=8056), III (n=4243), IVAnon-n1 (n=701), n1 (n=112), and IVB (n=266), and their long-term outcomes were compared., Results: The median follow-up period was 20.6 months. The 3-year overall survival rates of the patients with stage IVAnon-n1, stage n1, and stage IVB were 51.6%, 38.9% and 27.2%, respectively. A multivariate analysis showed that stage IVAnon-n1 would have a similar impact on the survival as stage n1 (hazard ratio: 0.88, 95% confidence interval: 0.59-1.33, P=0.555), and that stage n1 still represented one class less advanced than stage IVB (hazard ratio: 0.52, 95% confidence interval: 0.34-0.80, P=0.003)., Conclusions: The prognosis of patients with histologically node-positive HCC was similar to that of patients with locally advanced HCC (stage IVA), which supports the validity of the current Japanese staging system and also partially validates the system proposed by the UICC/AJCC.

Objective: Clinical staging is very important for optimal therapeutic strategy and prognostic prediction in patients with hepatocellular carcinoma (HCC). The Barcelona Clinic Liver Cancer (BCLC) staging system is the most widely used and best-validated method for HCC. Similarly, the conventional Japan Integrated Staging (c-JIS) score and the biomarker-combined JIS (bm-JIS) score have also been reported to effectively stratify HCC patients. The aim of this study was to evaluate the performance of these three staging systems for prognostic prediction., Methods: A total of 4,649 HCC patients were included in this study. A multivariate analysis identified the independent risk factors associated with overall survival. The stratification ability and the suitability as a prognostic model of the three staging systems were compared., Results: Multivariate analysis revealed that male sex, higher Child-Pugh score, tumor size >2.0 cm, multiple tumors, vascular invasion, higher alpha-fetoprotein (AFP) level, higher des-gamma-carboxyprothrombin level, higher Lens culinaris agglutinin-reactive AFP level, and a performance status of 3-4 were independent risk factors in HCC. The independent homogenizing ability and stratification value of the bm-JIS score were higher than those of the c-JIS score and the BCLC system (χ(2) = 972.7581, 758.1041 and 679.6832, respectively). Moreover, the bm-JIS score had the lowest Akaike Information Criteria value, followed by the c-JIS score and the BCLC system (9,844.278, 10,054.93 and 10,131.35, respectively)., Conclusions: Our results suggest that the bm-JIS score offers good stratification ability and is a better prognostic predictor than the c-JIS score and the BCLC system.

Background/aims: This study assessed the results of preoperative evaluation of ductal invasion by perihilar cholangiocarcinoma, imaged using 3-dimensional (3D) CT cholangiography compared to conventional endoscopic retrograde cholangiography (ERC) and magnetic resonance cholangiopancreatography (MRCP)., Methodology: ERC, MRCP and 3D-CT cholangiography were planned in 24 patients with preoperatively diagnosed perihilar cholangiocarcinoma. Evaluations of bile duct images using each of 3 modalities were classified into 2 groups (the Visualization uncertain (VU) group and the Visualization certain and clear (VCC) group) according to the quality of biliary images. The results of pathological assessments and preoperative radiological evaluations were compared., Results: In the bile duct evaluation, the rates between the 2 groups were not significantly different across the three modalities. 3D-CT cholangiography evaluated tumour involvement most clearly in patients with obstructive jaundice (p = 0.044), and ERC evaluated biliary tree more clearly compared to MRCP or 3D-CT cholangiography in patients without obstructive jaundice (p = 0.051). For evaluation of pathological tumor invasion in the VCC group, 3D-CT cholangiography enabled a correct diagnosis in 7 of 11 patients, and R0 resection was achieved in 8 of 11 patients., Conclusions: 3D-CT cholangiography offers accurate preoperative assessment of bile duct invasion by perihilar cholangiocarcinoma, especially in patients with obstructive jaundice.

We report a case of multiple bilobar hepatocellular carcinoma( HCC) that was successfully treated with a multidisciplinary treatment including preoperative percutaneous isolated hepatic perfusion and hepatectomy. The patient was a 61- year-old man who was detected as having HCC mainly in segment 4 and 8 of the liver and multiple bilobar intrahepatic metastasis during follow-up evaluation for chronic hepatitis B. Curative resection was difficult because the patient had insufficient liver function and because of the location of the tumor. Hence, we performed preoperative percutaneous isolated hepatic perfusion (PIHP) to control the multiple HCC. Seven weeks after the PIHP, the tumor size had reduced, and therefore we performed an extended left hepatic lobectomy. In addition to these treatment modalities, we performed transcatheter arterial chemoembolization (TACE) 3 times owing to recurrent HCC in the right liver lobe. Considering that HCC in segment 8 can be treated with TACE, we performed partial hepatectomy. As of the last follow-up visit, the patient was alive without disease recurrence. Thus, preoperative PIHP may improve the resectability rate in patients with multiple bilobar HCC for which curative resection is difficult to perform.

Background: The efficacy of hepatic arterial infusion chemotherapy for the treatment of advanced hepatocellular carcinoma (HCC) remains unclear., Methods: The outcome of 476 patients with HCC who underwent hepatic arterial infusion chemotherapy with 5-fluorouracil and cisplatin (HAIC) were compared with 1466 patients who did not receive active therapy., Results: A survival benefit of the therapy after adjusting for known risk factors was observed (hazard ratio, 0.48; 95% CI, 0.41-0.56; P<0.0001). In propensity score-matched analysis (n=682), median survival time was longer for patients who underwent chemotherapy (14.0 months) than for patients who did not receive active treatment (5.2 months, P<0.0001)., Conclusion: For advanced HCC, HAIC is considered to be an effective treatment.

Background & Aims: To clarify the biological behaviour of small hypovascular hepatocellular carcinoma (HCC) because of insufficient evidence even though frequently encountered., Methods: The study covered naïve 4,474 patients who met solitary HCC ≤ 3 cm (mean, 2.1 cm), histopathologically proven and Child Pugh A or B. Macroscopic vascular invasion and distant metastasis were excluded. The hypovascularity of tumour was defined as hypo- or iso-enhancement in arterial phase of multiple dynamic imaging techniques., Results: Of them, 802 (18%) were hypovascular. The ratio of hypovascular HCC decreased as tumour size increased (P < 0.001) and most of them developed to hypervascular type when they grew over 1.5 cm. Hypovascular group showed a significantly higher ratio of well differentiated grade (P < 0.001) and marginally less incidence of microvascular invasion and metastases compared with hypervascular group. The histologic dedifferentiation (less differentiation) developed step-by-step as tumour size increased in hyper- and even hypovascular group. The des-γ-carboxy prothrombin (DCP) value ≥ 300 mAU/ml was closely correlated with increase of tumour size in both groups. Logistic regression analysis revealed five variables were independent predictors for hypovascular HCC; tumour size ≤ 1.5 cm, alpha-fetoprotein < 200 ng/ml, DCP < 40 mAU/ml, well differentiated grade, and positivity for hepatitis C virus antibody., Conclusions: Hypovascular HCC was biologically less aggressive and developed with stepwise dedifferentiation and transformation to hypervascular appearance along with tumour growth. These results will help in leading correct diagnosis of small hypovascular tumour and assessing optimal treatment for hypovascular HCC ≤ 3 cm., (© 2013 John Wiley & Sons A/S.)

Lymphadenectomy of lymph node metastasis (LNM) from hepatocellular carcinoma (HCC) may potentially improve survival of patients with intrahepatic tumors controllable by means of locolegional treatment. However, the treatment strategy has not gained wide clinical acceptance, especially in patients with multiple advanced HCC. Thus, the purpose of this study is to evaluate the role of lymphadenectomy combined with locoregional treatment for the management of multiple advanced HCC with LNM. Between January 1998 and August 2012, 15 patients underwent a selective lymphadenectomy either concurrently or sequentially after hepatectomy. Seven of 15 patients underwent reductive hepatectomy while the remaining 8 patients had hepatectomy at curative intent. In patients with reductive hepatectomy, lymphadenectomy was concurrently performed and the residual intrahepatic tumors were treated thereafter with additional locoregional treatments consisting of transcatheter arterial chemoembolization, radiofrequency ablation, and percutaneous isolated hepatic perfusion. Only 4 patients (26.6%) of 15 patients developed lymph node recurrence. However, intrahepateic recurrence was encountered in 13 of 15 patients. The median survival time after lymphadenectomy was 25.2 months with the overall survival rates at 1, 2, and 3 years being 76.9%, 52.7%, and 26.4%, respectively. Selective lymphadenectomy and multimodal locoregional treatment in patients with multiple residual tumors exhibited a similar overall survival to complete resection of LNM and intrahepatic tumors (P=0.78). Lymphadenectomy combined with an additional aggressive locoregional treatments may be justified in selected patients with multiple advanced HCC with LNM.

Background & Aims: The treatment of choice for early or moderately advanced hepatocellular carcinoma (HCC) with good liver function remains controversial. We evaluated the therapeutic impacts of surgical resection (SR), percutaneous ethanol injection (PEI), and radiofrequency ablation (RFA) on long-term outcomes in patients with HCC., Methods: A database constructed on the basis of a Japanese nationwide survey of 28,510 patients with HCC treated by SR, PEI, or RFA between 2000 and 2005 was used to identify 12,968 patients who had no more than 3 tumors (≤ 3 cm) and liver damage of class A or B. The patients were divided into SR (n=5361), RFA (n=5548), and PEI groups (n=2059). Overall survival and time to recurrence were compared among them., Results: Median follow-up was 2.16 years. Overall survival at 3 and 5 years was respectively 85.3%/71.1% in the SR group, 81.0%/61.1% in the RFA, and 78.9%/56.3% in the PEI. Time to recurrence at 3 and 5 years was 43.3%/63.8%, 57.2%/71.7%, and 64.3%/76.9%, respectively. On multivariate analysis, the hazard ratio for death was significantly lower in the SR group than in the RFA (SR vs. RFA:0.84, 95% confidence interval, 0.74-0.95; p=0.006) and PEI groups (SR vs. PEI:0.75, 0.64-0.86; p=0.0001). The hazard ratios for recurrence were also lower in the SR group than in the RFA (SR vs. RFA:0.74, 0.68-0.79; p=0.0001) and PEI groups (SR vs. PEI:0.59, 0.54-0.65; p=0.0001)., Conclusions: Our findings suggest that surgical resection results in longer overall survival and time to recurrence than either RFA or PEIin patients with HCC [corrected]., (Copyright © 2012. Published by Elsevier B.V.)

The purpose of this study was to assess the efficacy of arterial-dominant phase images of gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (EOB)-enhanced magnetic resonance imaging (MRI) for evaluation of arterial blood supply in hepatocellular carcinoma (HCC) in comparison with that of multiphasic dynamic computed tomography (CT). This study comprised 30 patients (22 men and 8 women, mean age: 68.0 years) with 40 pathologically proven HCCs (well differentiated: 3, moderately differentiated: 30, poorly differentiated: 7, mean diameter: 45.1 mm), all of whom underwent EOB-enhanced MRI and dynamic CT preoperative assessment. Regions of interest were placed over HCCs and the adjacent normal liver, and signal intensities or CT values were measured by two experienced abdominal radiologists on the arterial-dominant phase images of EOB-enhanced MRI and dynamic CT images. HCC-to-liver contrasts [Michelson's contrast: C(M)=(S(HCC)-S(Liver))/(S(HCC)+S(Liver))] were calculated and compared among the modalities. HCC-to-liver contrasts were also visually scored on a 5-point scale and compared. The mean C(M) and visual score for dynamic CT were significantly higher than those for EOB-enhanced MRI. Good agreements were obtained among the two observers. Dynamic CT is a more suitable modality than EOB-enhanced MRI for evaluation of arterial blood supply in HCC. This should be taken into account for diagnosis and management of HCC., (Copyright © 2013 Elsevier Inc. All rights reserved.)

We report a case of bilobar multiple hepatocellular carcinoma (HCC) successfully treated by preoperative percutaneous isolated hepatic perfusion(PIHP) and subsequent hepatectomy. A 77-year-old man with elevated serum PIVKA-II level and hepatomas was referred to our hospital. Abdominal dynamic computed tomography and gadoxetate disodium-enhanced magnetic resonance imaging demonstrated advanced HCCs: 11 tumors with a maximum tumor size of 4.8 cm diameter in the right lobe, and 1 tumor of 3.6 cm diameter in the left lobe. Curative resection was impossible due to insufficient liver function and due to the locations of the tumors. Therefore, we performed preoperative PIHP in order to control the multiple HCCs in the right lobe. This resulted in normalization of serum PIVKA-II level and complete necrosis of all tumors in the right lobe, as observed on dynamic computed tomography after 4 weeks of PIHP. Then, at 7 weeks after PIHP, we performed extended left lobectomy for residual tumor in the left lobe. Finally, complete remission was thought to have been achieved. The patient is alive 6 months after PIHP, without recurrence.

We report a case of postoperative liver metastasis arising from pancreatic carcinoma treated with a novel procedure that we developed-percutaneous isolated hepatic perfusion (PIHP). A 69-year-old man diagnosed with pancreatic body cancer(pT3, pN0, pStage III) was treated using distal pancreatectomy and adjuvant therapy with gemcitabine(GEM). Six months later, a metastasis to the medial segment of the liver was found using computer tomography(CT). The patient was treated by chemotherapy with S-1, but the liver metastasis grew, and we therefore employed PIHP as the third-line therapy, using 80 mg doxorubicin (DXR) and 62 mg mitomycin C (MMC). Six weeks after PIHP, the tumor marker carbohydrate antigen 19-9( CA19-9) had decreased from 44,469 to 4,268 U/mL, and the carcinoembryonic antigen(CEA) level decreased from 28.8 to 5.4 U/mL. Although the size of the carcinoma remained the same on CT, some cells had liquefied as a result of necrosis. However, the patient died about 1 year after PIHP due to the growth of liver metastasis, peritoneal metastasis, and local recurrence, reflected by a progressively increasing level of tumor marker. In this case, PIHP seemed to be ineffective due to local recurrence and peritoneal metastasis as well as early enlargement of liver metastasis. However, the reduction in tumor marker levels and the observed tumor necrosis, suggest that PIHP is a potentially effective and promising treatment for liver metastasis arising from pancreatic carcinoma.

Background & Aims: Transcatheter arterial chemoembolization with lipiodol (TACE) is widely performed in patients with hepatocellular carcinoma (HCC) unsuitable for curative treatment. It has recently been recommended for patients with 2 or 3 tumors >3 cm or ≥4 tumors in a treatment algorithm proposed by Japanese guidelines. However, the best indication and appropriateness of the algorithm for TACE are still unclear., Methods: In 4966 HCC patients who underwent TACE, survival was evaluated based on tumor number, size and liver function; and the adequacy of the algorithm for TACE was validated. Exclusion criteria were: vascular invasion, extrahepatic metastasis, and prior treatment. The mean follow up period was 1.6 years., Results: The overall median and 5-year survivals were 3.3 years and 34%, respectively. Multivariate analysis revealed that Child-Pugh class, tumor number, size, alpha-fetoprotein, and des-gamma carboxy-prothrombin were independent predictors. The survival rate decreased as the tumor number (p=0.0001) and size increased (p=0.04 to p=0.0001) in all but one subgroup in both Child-Pugh-A and -B. The stratification of these patients to four treatments in the algorithm showed potential ability to discriminate survivals of the resection and ablation (non-TACE) groups from those of the TACE group in Child-Pugh-B and partially in A., Conclusions: TACE showed higher survival rates in patients with fewer tumor numbers, smaller tumor size, and better liver function. The treatment algorithm proposed by the Japanese guidelines might be appropriate to discriminate the survival of patients with non-TACE from TACE therapy., (Copyright © 2011 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

We have developed a novel insertion method, a non-trocar technique (NTT), for laparoscopic radiofrequency ablation, whereby an ablation needle, guided by a 14.8-mm echo probe (PVM-787LA; Toshiba, Tokyo, Japan), accurately and easily punctures the target tumor in the liver. By existing methods, an ablation needle is inserted into the abdominal cavity through a puncture hole away from the echo probe because of the presence of a 15-mm trocar. Under such circumstances, fitting and sliding an ablation needle along the groove of the probe into the abdominal cavity is difficult because of the longitudinal dissociation between the needle and the probe. To avoid this dissociation, an echo probe is inserted directly through the small incision from which the 12-mm trocar is withdrawn and an ablation needle is introduced directly into the abdominal cavity through a puncture hole adjacent to and slid along the groove of the probe., (Copyright © 2012 S. Karger AG, Basel.)

Background: The objective of this study was to evaluate the clinical outcome of proton and carbon ion therapy for hepatocellular carcinoma (HCC)., Methods: In total, 343 consecutive patients with 386 tumors, including 242 patients (with 278 tumors) who received proton therapy and 101 patients (with 108 tumors) who received carbon ion therapy, were treated on 8 different protocols of proton therapy (52.8-84.0 gray equivalents [GyE] in 4-38 fractions) and on 4 different protocols of carbon ion therapy (52.8-76.0 GyE in 4-20 fractions)., Results: The 5-year local control and overall survival rates for all patients were 90.8% and 38.2%, respectively. Regarding proton and carbon ion therapy, the 5-year local control rates were 90.2% and 93%, respectively, and the 5-year overall survival rates were 38% and 36.3%, respectively. These rates did not differ significantly between the 2 therapies. Univariate analysis identified tumor size as an independent risk factor for local recurrence in proton therapy, carbon ion therapy, and in all patients. Multivariate analysis identified tumor size as the only independent risk factor for local recurrence in proton therapy and in all patients. Child-Pugh classification was the only independent risk factor for overall survival in proton therapy, in carbon ion therapy, and in all patients according to both univariate and multivariate analyses. No patients died of treatment-related toxicities., Conclusions: Proton and carbon ion therapies for HCC were comparable in terms of local control and overall survival rates. These therapies may represent innovative alternatives to conventional local therapies for HCC., (Copyright © 2011 American Cancer Society.)

We report a case of multiple advanced hepatocellular carcinomas (HCC) with bilobar distribution treated by combination therapy of hepatectomy and particle therapy (carbon ion therapy). A 73-year-old man who had been pointed out hepatic tumors on abdominal CT was referred to our hospital in February 2010. Advanced HCCs; 8 cm Vp3 and 6 cm in the left lobe, 4 cm in the posterior segment, and 1 .5 cm in the S8 area, were detected by abdominal dynamic CT and EOB-MRI etc. Curative resection was not applied due to insufficiency of liver function and unfavorable anatomical tumor locations. Accordingly we have developed a novel combination therapy of hepatectomy and particle therapy. First we performed left lobectomy in March 2010, followed by administration of particle therapy to the posterior segment for local control in May. Then, transcatheter arterial chemoembolization was administered 4 times for residual tumors. The patient survives for 15 months after the initial therapy with good local control.

In December 2008, a 43-year-old male who had been pointed out a nodular shadow in the right upper field on a chest radiography was admitted to hospital. A 35 mm mass infiltrating to superior vena cava in the right upper lobe of the lung, and 32 mm mass in the liver at S7 were detected by CT. Pathological diagnosis of the liver tumor was adenocarcinoma. Under the diagnosis of lung carcinoma and liver metastasis, systemic chemotherapy was started from January 2009. Radiofrequency ablation (RFA) therapy was added for liver S7 mass in February, and radiation therapy was performed for lung mass in December. The lung lesion has markedly reduced, but the liver lesion recurred in October 2009, which continued to grow up to 80 mm until August 2010. He presented to our hospital with the diagnosis of liver metastasis of controlled primary lung cancer. In October, we performed right hepatectomy with diaphragma and right lung resection. The pathological diagnosis was intrahepatic cholangiocarcinoma. Multiple recurrences in remnant liver, lung and peritoneal metastasis were detected in January 2011. For intrahepatic cholangiocarcinoma, hepatectomy is the only established treatment, and RFA treatment remains controversial. Clinical diagnosis of multiple cancers should be decided with caution.

Background: The prognosis of patients who have hepatocellular carcinoma (HCC) associated with inferior vena cava tumor thrombus (IVCTT) is very poor, and effective treatment modalities are extremely limited. The objective of this study was to determine the therapeutic efficacy of particle radiotherapy for HCC with IVCTT., Methods: Between June 2001 and January 2009, 16 evaluable patients who had HCC with IVCTT were treated with particle radiotherapy. They were divided into 2 groups: 6 were treated with curative intent; 10 with palliative intent. The local tumor control rates, overall survival rates, and toxicities were evaluated., Results: All tumors treated with particle radiotherapy remained controlled without local recurrence at the last follow-up. The overall survival rates for the 16 patients at 1 and 3 years were 61.1 and 36.7%, respectively. We observed a significant difference in the survival rates according to treatment policy. The median survival time was 25.4 months for patients treated with curative intent and 7.7 months for those treated with palliative intent. The one-year survival rates were 100.0 and 33.3%, respectively. No Grade 3 or higher treatment-related toxicities were observed., Conclusions: Particle radiotherapy is thought to be potentially effective and safe for HCC with IVCTT. Considering the current lack of effective and less-invasive local therapy for HCC with IVCTT, particle radiotherapy may therefore be an attractive new therapeutic approach for this type of HCC.

Background: Particle radiotherapy is a novel treatment for malignant tumours. The present study aimed to evaluate risk factors for overall survival and local control after particle radiotherapy of single small hepatocellular carcinoma (HCC), and to identify suitable candidates for this treatment., Methods: All patients with a single HCC smaller than 5 cm in diameter treated by particle radiotherapy between 2001 and 2008 were identified retrospectively from a prospectively collected database. Clinical outcomes and prognostic factors were analysed., Results: A total of 150 patients were included. Five-year overall survival and local control rates were 50.9 and 92.3 per cent respectively. Multivariable analysis revealed that several factors, including age and Child-Pugh classification, significantly influenced overall survival. Proximity to the digestive tract and Child-Pugh classification were independent risk factors for local recurrence. Other tumour factors including size, gross classification, previous treatment, macroscopic vascular invasion, and tumour location in relation to the diaphragm and large vessels did not influence local control rate., Conclusion: Particle radiotherapy seems safe and effective, and may be a novel treatment for small HCC. Recurrences are more frequent when the tumour is located close to the gut., (Copyright © 2011 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.)

A 45-year-old man was admitted to our hospital with a chief complaint of anal bleeding. Colonoscopy revealed a lower rectal tumor diagnosed as rectal carcinoid on biopsy. Multiple metastatic liver tumors were found on abdominal CT scan. We performed an abdomino-perineal resection, a partial hepatectomy, and TACE. There seemed to be no apparent residues of a carcinoid tumor on abdominal CT. About one year after the first therapy, CT scan had revealed multiple metastases to the liver, lymph nodes and bones. Therefore, we started an octreotide LAR, which remarkably reduced the size of metastatic tumors. The treatment of an octreotide LAR had controlled the progression of metastatic tumors for two and half years. In this case, the effect of an octreotide LAR for recurrence of rectal carcinoid after local therapies brought good controls of symptoms and an inhibition of tumor growth for long-term.

We report a long-term survival case of hepatocellular carcinoma (HCC) with recurrence in the liver and multiple lymph nodes treated with lymph node dissection and percutaneous isolated hepatic perfusion (PIHP). The patient was a 70-year-old man with HCC. In 1999, transcatheter arterial chemoembolozation (TACE) was performed for HCCs. In 2000, partial hepatectomy was achieved for a recurrence in the liver. In 2002, CT scan disclosed multiple lymph node metastases around the hepatic artery and the recurrence in the liver. We performed a lymph node dissection and radio-frequency ablation for the hepatic tumor. After the operation, PIHP was performed for residual lymph node metastases. Then, a recurrence in the liver occurred 3 times, but was treated successfully with local therapy. The patient survives for 10 years after the initial therapy, and 8 years after a lymph node dissection.

We herein report a case of advanced hepatocellular carcinoma (HCC) with Vp4 portal vein thrombosis (PVTT). All of the hepatic tumors have completely disappeared for more than two years by a dual treatment with reductive surgery plus percutaneous isolated hepatic perfusion (PIHP). A 68-year-old man was referred to our institution in May 2009. The abdominal CT scan demonstrated massive HCC in the right robe of the liver with PVTT reaching the portal trunk (Vp4). We semi-electively performed a right hepatectomy together with thrombectomy of the PVTT. Subsequently, we underwent a PIHP (doxorubicin 90 mg/m2). This resulted in normalization of serum AFP and PIVKA-II levels. Dual treatment is considered to be the strongest therapeutic modality for multiple advanced HCC with severe PVTT.

Few potentially curative treatment options exist apart from hepatic resection for patients with huge hepatocellular carcinoma (HCC). Proton radiotherapy is a promising new modality which has an inherent anti-tumor effect against HCC. However, the application of proton radiotherapy for tumors adjacent to the gastrointestinal tract is restricted because the tolerance dose of the intestine is extremely low. A novel two-step treatment was developed with surgical spacer placement and subsequent proton radiotherapy to administer proton radiotherapy with curative intent. This report presents a case of a patient with a huge unresectable HCC treated by this method who achieved disease-free survival of more than 2 years. This new strategy may potentially be an innovative and standard therapy for unresectable HCC in the near future.

We report a case of hemangioma with an atypical vascular enhancement pattern. The hemangioma showed peripheral rim enhancement at the arterial phase during dynamic magnetic resonance imaging, and the peripheral enhanced zone was still apparent during the delayed phase, as shown on double-phase computed tomography hepatic arteriography. The rim enhancement pattern of this case, mimicking that of hepatocellular carcinoma, may be due to the surrounding liver parenchymal fibrotic change caused by an active hepatitis C viral infection.

A 69-year-old man diagnosed as having gallbladder cancer with liver invasion and metastasis to Couinaud's hepatic segment 8 (S8) was referred to our hospital. Because of the presence of liver metastasis, gemcitabine administration was chosen. Although gemcitabine was effective for the liver metastasis, his serum carcinoembryonic antigen (CEA) level had gradually increased after 12 cycles of gemcitabine administration. There was no distant metastasis other than the liver metastasis (manageable with gemcitabine) on detailed radiological examination. Therefore, we performed surgery for the primary lesion, after obtaining informed consent. Pathological examination demonstrated viable cancer cells with necrosis and fibrosis in the gallbladder, and fibrosis without viable cancer cells in the induration in liver S8. Gemcitabine was re-administered as postoperative adjuvant chemotherapy. Twenty months after the surgery, there was no sign of recurrence. In selected patients, gemcitabine treatment may be effective against gallbladder cancer with metastasis.

A 61-year-old male was admitted for advanced hepatocellular carcinoma (HCC) with multiple lung metastases and tumor thrombus in the portal vein and superior vena cava. At first, we planned to perform transcatheter arterial embolization (TAE) to avoid the rupture of the liver tumor. But, due to the severe liver dysfunction, ie Child-Pugh C and 36% ICG R15, hepatic arterial infusion (HAI) of epirubicin 40 mg was performed. After that, the patient was followed at the outpatient ward and his general condition has gradually improved without a special treatment. At the present, one year and ten month after HAI, the serum alpha-fetoprotein (AFP) is almost within normal limits and CT scans show that HCC with multiple lung metastases, and tumor thrombus in the portal vein and superior vena cava almost disappeared. Although, spontaneous regression of HCC was a rare phenomenon, it might have played a major role in the good anticancer efficacy of this patient as well as high anti-cancer agent sensitivity of his liver tumor.

For patients with multiple bilobar hepatocellular carcinoma (m-HCC) and/or advanced portal venous tumor thrombus (Vp3, 4), there has been no effective therapy, and the survival of more than 6 months was exceptional. Under these circumstances, we have developed a dual treatment (dual Tx) that combines reductive hepatectomy with percutaneous isolated hepatic perfusion (PIHP) for such patients. This dual Tx offers the high-rate of mid- and long-term survival in a subset of patients who had previously a dismal prognosis. Herein, we report a patient with Vp4 m-HCC who was successfully treated with dual Tx and survived for more than 2 years with a complete remission of hepatic tumors. A 53-year-old man had main tumors in the right lobe liver and multiple bilobar intrahepatic metastases (IM) with portal venous tumor thrombus reaching the portal trunk. He underwent an extended right hepatectomy with portal venous tumor thrombectomy, and subsequently PIHP twice in a 3-month period after reductive hepatectomy. After dual Tx, he had sustained complete remission for more than 2 years. He died because of obstruction of the superior vena cava by recurrent tumors in the mediastinum. His clinical course after treatment strongly indicates that the dual Tx should become a major treatment option for patients with Vp3, 4 m-HCC.

We herein report a case of multiple advanced hepatocellular carcinoma (HCC) with rapidly progressing portal vein tumor thrombosis (PVTT). All of the hepatic tumors have completely disappeared for more than two years by a dual treatment with reductive surgery plus percutaneous isolated hepatic perfusion (PIHP). A 55-year-old man was referred to our institution on June 30, 2003. The abdominal CT scan demonstrated multiple massive HCC in the entire liver with PVTT reaching the portal trunk (Vp4). Two weeks later, the PVTT rapidly progressed to the umbilical portion of the left portal vein, and to the confluence of the superior mesenteric vein and to the splenic vein. Thus, we semi electively performed an extended right hepatectomy together with thrombectomy of the PVTT. Subsequently, he underwent a repeated PIHP (1st; doxorubicin 90 mg/m2, 2nd doxorubicin 65 mg/m2). This treatment produced complete tumor clearance of all of the residual tumors in the left liver. In March 2005, he underwent partial pneumonectomy for a metastatic lung. This again resulted in normalization of serum AFP and PIVKA-II levels. Dual treatment is considered to be the strongest therapeutic modality for multiple advanced HCC with severe PVTT. In addition, a close follow-up is required because in such far advanced cases, metastatic lesions most likely recur in the liver but also in the distant organs.

Objective: To evaluate the efficacy of a novel 2-stage treatment with reductive surgery plus percutaneous isolated hepatic perfusion (PIHP) for multiple hepatocellular carcinoma (HCC), which was previously unresectable., Summary Background Data: Surgical resection is the treatment of choice for HCC, but the majority of patients with advanced HCC are not suitable candidates. PIHP is a minimally invasive surgery that allows high-dose regional chemotherapy of the liver, and our phase II studies have shown its profound efficacy for the local control of advanced HCC., Methods: Twenty-five patients with multiple advanced HCC were enrolled in this prospective study. In the first stage, all patients underwent reductive hepatectomy: major hepatectomy in 13 patients and segmentectomy or less in 12. In 2 patients with subsegmentectomy, the retropancreatic and periportal metastatic lymph nodes were synchronously resected. Regardless of the type of hepatectomy, all patients routinely underwent cholecystectomy, and ligations of the right gastric artery and arterial collaterals of the remnant liver to increase the safety and efficacy of PIHP. In the second stage, PIHP with doxorubicin 60-120 mg/m2/treatment was planned for a period of 1 to 3 months after surgery., Results: Of 25 enrolled patients, 22 successfully underwent PIHP an average of 1.8 times for the local control of residual liver tumors. In the remaining 3 patients, PIHP was abandoned because 2 had rapid disease progression and 1 had liver failure after surgery. In 22 patients with the 2-stage treatment, 19 (86%) had objective local tumor control (10 complete remissions and 9 partial responses with a median response duration of 16 months). The actuarial survival rate of all 25 patients was 42% at 5 years., Conclusions: Reductive surgery plus PIHP produced a strong antitumoral effect on multiple advanced HCC, when liver function allows this concentrated treatment approach, and offers long-term survival in a subset of patients who were previously deemed to have unresectable disease.