Nutritional impact of active hexose-correlated compound for patients with resectable or borderline-resectable pancreatic cancer treated with neoadjuvant therapy.

Active hexose-correlated compound (AHCC) is a standardized extract from cultured Lentinula edodes mycelia, used as a potent biological response modifier in cancer treatment. We evaluated the nutritional effect of AHCC, given during neoadjuvant therapy, to patients with pancreatic ductal adenocarcinoma (PDAC). Thirty patients with resectable or borderline-resectable PDAC received neoadjuvant therapy with gemcitabine plus S-1. We compared, retrospectively, the outcomes of 15 patients who received AHCC combined with neoadjuvant therapy with those of 15 patients who did not receive AHCC combined with neoadjuvant therapy. The median changes of the neutrophil-to-lymphocyte ratio (NLR) and prognostic nutrition index (PNI) were significantly better in the AHCC group. The relative dose intensity of neoadjuvant therapy was also significantly higher in the AHCC group. Thus, AHCC may improve the nutritional status during neoadjuvant therapy of patients with pancreatic ductal adenocarcinoma. To validate these results and examine the long-term impact of AHCC, a prospective phase II study for PDAC is ongoing.

Hepatic Resection Followed by Hepatic Arterial Infusion Chemotherapy for Hepatocellular Carcinoma with Intrahepatic Dissemination.

BACKGROUND/AIM: To investigate the utility of adjuvant hepatic arterial infusion chemotherapy (HAIC) following hepatectomy for patients with hepatocellular carcinoma (HCC) with intrahepatic dissemination (IHD) after local ablation therapy. PATIENTS AND METHODS: Twelve patients with HCC with IHD were divided into two groups: HAIC group (n=6) underwent hepatectomy followed by HAIC; and the non-HAIC group (n=6) underwent hepatectomy alone. HAIC with cisplatin and 5-fluorouracil was started within a month and was continued for a month: Results: At the first local ablation, tumors close to the major portal vein and insufficient ablation were recognized in eight (67.7%) and six (58.3%) of the patients, respectively. In the HAIC group, the 1-, 3-, and 5-year disease-free and overall survival rates were 50.0%, 16.7%, and 16.7%, and 83.3%, 83.3% and 62.5%, respectively. Three patients in the HAIC group remain alive after 10 years of follow-up. CONCLUSION: Hepatic resection with short-term postoperative HAIC may provide excellent outcomes in patients with HCC and IHD.

Impact of surgical treatment after sorafenib therapy for advanced hepatocellular carcinoma.

BACKGROUND: For advanced hepatocellular carcinoma (HCC), surgical treatment after sorafenib induction has rarely been reported. We examined the survival benefit of additional surgical treatment in sorafenib-treated patients. METHODS: Thirty-two advanced HCC patients were given sorafenib from July 2009 to July 2012, and we statistically analyzed the relevant predictive factors of the long-term survival. The institutional review board of Kumamoto University Hospital approved this study (Approval number 1038). RESULTS: The median duration of sorafenib administration was 56.5 days (range 5-945). The cumulative overall survival rate was 44.6, 33.4, 26.0 and 17.8% at 1, 2, 3 and 5 years, respectively. The median survival time was 11.2 months. A survival of more than 3 years after the initiation of sorafenib induction was observed in seven patients, five of whom were subjected to additional surgical intervention. Additional surgery was the most significant factor predicting a survival exceeding 3 years (P < 0.0001) and represents an independent prognostic factor [hazard ratio (HR) 0.07; P = 0.01], followed by the total dose of sorafenib. The surgical interventions comprised two hepatic resections ± radiofrequency ablation, two radiofrequency ablations and one lung resection. CONCLUSIONS: A long-term survival might be obtained for select HCC patients given adequate additional surgical treatment, even after sorafenib induction.

A long-term survivor of hilar cholangiocarcinoma with resection of recurrent peritoneal dissemination after R0 surgery: a case report.

BACKGROUND: Although hilar cholangiocarcinoma (HCCA) has a very poor prognosis, there are cases in which long-term survival is rarely obtained by multidisciplinary treatment. CASE PRESENTATION: A 61-year-old man diagnosed with HCCA was referred to our hospital. We performed an extended left hemi-hepatectomy and caudate lobectomy with extrahepatic bile duct resection. The tumor stage was T2aN0M0, stage II, based on the TNM classification, seventh edition. R0 resection was successfully performed. Adjuvant chemotherapy was not administered. After 38 months, computed tomography revealed peritoneal dissemination. The patient received chemotherapy with tegafur-gimeracil-oteracil-potassium (S-1) and gemcitabine. The peritoneal dissemination was successfully controlled for more than 50 months. During the treatment, levels of CEA and CA19-9 kept rising slowly, which was followed by bowel obstruction due to peritoneal dissemination of HCCA. The patient underwent resection of transverse colon with tumor nodules, and the tumor was pathologically diagnosed as metastasis of HCCA. Tumor markers decreased to normal levels, and the patient has been free from tumor relapse for 6 months. CONCLUSIONS: We here report a rare case of HCCA patient with recurrent peritoneal dissemination 3 years after R0 surgery which was sensitive to chemotherapy. The patient successfully received resection of peritoneal dissemination 50 months after the induction of chemotherapy and survived for 10 years.

Statin attenuates cell proliferative ability via TAZ (WWTR1) in hepatocellular carcinoma.

Diabetes and obesity are associated with non-alcoholic steatohepatitis and an increased incidence of hepatocellular carcinoma (HCC). TAZ and YAP are equivalently placed downstream effectors of the Hippo pathway with oncogenic roles in human cancers. Statins are commonly used to patients with metabolic problems as hypercholesterolemia. Statins also have anti-cancer properties, and the cross-talk between mevalonate pathway and Hippo pathway was known. The aim of this study is to confirm the statin's anti-cancer effects on HCC cells and its survival benefits in HCC patients with curative surgery. TAZ expression level in HCC cell lines was analyzed by western blot. Two cell lines (HLF and HuH1) were used in this study. Then the mechanism of statin's anti-proliferative effect was examined in HLF and HuH1 cells. In clinical setting, overall survival and recurrence-free survival (RFS) rate were examined in comparison between statin intake and statin non-intake group. The proliferation assay using four different statins (atorvastatin, pravastatin, fluvastatin, simvastatin). Simvastatin and fluvastatin showed very strong growth suppressive effects, and induced apoptosis in HLF cells, but not HuH1 cells. TAZ expression was suppressed in HLF cells by fluvastatin and simvastatin treatment. The similar change pattern was confirmed in p-ERK1/2 and ERK. In HuH1 cells, such expression change was not confirmed. In clinical setting, statin intake was significantly associated with longer RFS in the HCC patients with hepatectomy (P = 0.038). The statin had the anti-proliferative effects and induced apoptosis in HCC cells and improved the prognosis of HCC patients.

Effect of branched-chain amino acid supplementation on functional liver regeneration in patients undergoing portal vein embolization and sequential hepatectomy: a randomized controlled trial.

BACKGROUND: Portal vein embolization (PVE) can decrease the resection ratio for major hepatectomy. (99m)Tc-galactosyl human serum albumin (GSA) scintigraphy is useful for evaluating quantitative functional liver volume. Branched chain amino acids (BCAAs) modulate liver function and regeneration. We analyzed the effects of BCAAs, in terms of liver function and regeneration after PVE, in combination with major hepatectomy. METHODS: This randomized controlled trial was conducted for patients receiving PVE through to complete hepatectomy from September, 2011 to June, 2013. BCAA granules were added two times a day to a conventional diet in the BCAA administration group (BCAA group). The primary end point was functional liver regeneration of the future remnant liver after PVE followed by hepatic resection. Functional liver regeneration was assessed by the liver uptake value obtained from (99m)Tc-GSA scintigraphy single-photon-emission computed tomography/computed tomography fusion images. The secondary end points were volumetric liver regeneration and changes in liver function and laboratory data. RESULTS: A BCAA group (n = 13) and a non-BCAA group (control group; n = 15) were included. The primary end point was partially met: the liver uptake value significantly increased in the BCAA group compared with the control group 6 months after hepatic resection (266.7% vs 77.6%, P = 0.04) and marginally increased after PVE (43.8% vs 17.4%, P = 0.079). Following PVE, the increment of the uptake ratio of the liver to the liver plus heart at 15 min was significantly less in the BCAA group than in the control group (0.0 and 0.01, P = 0.023). CONCLUSIONS: BCAA supplementation improved functional liver regeneration and function in patients undergoing PVE followed by major hepatic resection.