Preventing Recurrence of Hepatocellular Carcinoma After Curative Hepatectomy With Active Hexose-correlated Compound Derived From Lentinula edodes Mycelia.

PURPOSE: Active hexose-correlated compound (AHCC), a standardized extract of cultured Lentinula edodes mycelia, exerts antitumor effects through anti-inflammatory and immune-modulatory functions. Adjuvant therapy for patients with hepatocellular carcinoma (HCC) who have undergone curative hepatectomy has not been established. The purpose of this study was to evaluate the efficacy and safety of AHCC as adjuvant therapy in patients with advanced HCC after curative hepatectomy. PATIENTS AND METHODS: The study design was single-armed, non-randomized, open (no one was blinded), and uncontrolled. Patients with HCC who underwent curative hepatectomy were treated with AHCC (1 g) 3 times daily orally for 2 years. The inclusion criteria were HCC diagnosed preoperatively as stages A and B of the Barcelona clinic liver cancer (BCLC) classification and alpha-fetoprotein × protein induced by vitamin K absence or antagonist II (PIVKA-II) ≥ 105 for stage A. RESULTS: A total of 29 patients were treated with AHCC, of which 25 (4 patients discontinued) were followed up. The 2-year recurrence-free survival rate after resection was 48% for those without discontinuations and 55.2% for all patients with a history of treatment. Serum albumin levels decreased to a minimum in the first postoperative month and gradually recovered to the preoperative level at 6 months. Almost no change in lymphocyte percentage was observed during follow-up. Inflammation-based prognostic scores were maintained at favorable levels after hepatectomy. Toxicity and adverse events were not observed in any patient. CONCLUSION: AHCC may be safe and effective in preventing HCC recurrence after curative hepatectomy, and further randomized trials of AHCC for its use in this setting are warranted.This clinical trial was registered in UMIN Clinical Trials Registry (ID UMIN000024396).

Combined treatment of an aortosplenic bypass followed by coil embolization in the treatment of pancreaticoduodenal artery aneurysms caused by median arcuate ligament compression: a report of two cases.

BACKGROUND: Pancreaticoduodenal artery aneurysms (PDAAs) are rare visceral aneurysms, and prompt intervention/treatment of all PDAAs is recommended at the time of diagnosis to avoid rupture of aneurysms. Herein, we report two cases of PDAA caused by the median arcuate ligament syndrome, treated with surgical revascularization by aortosplenic bypass followed by coil embolization. CASE PRESENTATION: Case 1 A 54-year-old woman presented with a chief complaint of severe epigastralgia and was diagnosed with two large fusiform inferior PDAAs and celiac axis occlusion. To preserve the blood flow of the pancreatic head, duodenum, liver, and spleen, we performed elective surgery to release the MAL along with aortosplenic bypass. At 6 days postoperatively, transcatheter arterial embolization was performed. At the 8-year 6-month follow-up observation, no recurrent perfusion of the embolized PDAAs or rupture had occurred, including the non-embolized small PDAA, and the bypass graft had excellent patency. Case 2 A 39-year-old man who had been in good health was found to have a PDAA with celiac stenosis during a medical checkup. Computed tomography and superior mesenteric arteriography showed severe celiac axis stenosis and a markedly dilated pancreatic arcade with a large saccular PDAA. To preserve the blood flow of the pancreatic arcade, we performed elective surgery to release the MAL along with aortosplenic bypass. At 9 days postoperatively, transcatheter arterial embolization was performed. At the 6-year 7-month follow-up observation, no recurrent perfusion or rupture of the PDAA had occurred, and the bypass graft had excellent patency. CONCLUSION: Combined treatment with bypass surgery and coil embolization can be an effective option for the treatment of PDAAs associated with celiac axis occlusion or severe stenosis.

Portal Annular Pancreas With Common Hepatic Artery Trajectory Abnormality: A Case Report and Review of the Literature.

ABSTRACT: Portal annular pancreas (PAP) is a rare congenital pancreatic anomaly, in which the uncinate process of the pancreas fuses to the body of pancreas behind the portal vein. Here, we report a case of PAP with common hepatic arterial anomaly, which was identified during surgery. A 57-year-old man who had branch type intraductal papillary mucinous neoplasm in the head of the pancreas developed a nodule in the cystic lesion. We planned pylorus preserving pancreaticoduodenectomy. The common hepatic artery from the celiac artery passing behind the portal vein was revealed in preoperative examinations. During surgery, we discovered that the uncinate process of the pancreas was fused with the body of the pancreas behind the portal vein. We divided the pancreas at the anterior and posterior of the portal vein. The main pancreatic duct was present in the anterior pancreatic stump. We performed pancreaticojejunostomy in the anterior stump and closed the posterior stump by interrupted suture. Forty-four surgical cases of PAP have been reported in the English medical literature. There are few previous reports of PAP which involved an arterial anomaly. Clinicians should consider PAP preoperatively to ensure that the surgeon can appropriately plan pancreatic resection to avoid postoperative complications.

Role of Wnt5a in suppressing invasiveness of hepatocellular carcinoma via epithelial-mesenchymal transition.

Inappropriate activation of the canonical Wnt signaling pathway is associated with progression of hepatocellular carcinoma (HCC). However, the association between the non-canonical pathway activated by Wnt5a and HCC is not well known. The present study investigated the significance of Wnt5a expression in HCC. Immunohistochemical staining of Wnt5a was performed on specimens from 243 patients who underwent hepatic resection for HCC. The present study investigated whether Wnt5a expression was associated with clinical and pathological factors and prognosis. Wnt5a expression in human HCC cell lines was investigated using western blotting. The effects of overexpression or knockdown of Wnt5a were evaluated using proliferation and invasion assays. Changes in epithelial-mesenchymal transition (EMT)-related molecules were investigated using western blotting. Wnt5a negativity was significantly associated with poor tumor differentiation and positive vascular invasion. In univariate analysis, Wnt5a negativity was identified as a significant prognostic factor for overall survival (OS). Multivariate analysis of OS demonstrated that Wnt5a negativity was an independent prognostic factor. Wnt5a expression was lower in HLE and HLF cells than in HepG2 and Huh7 cells. Knockdown of Wnt5a by short hairpin RNA transfection increased the proliferation and invasiveness of Huh7 cells, and decreased the expression levels of E-cadherin. In HLF cells, overexpression of Wnt5a inhibited invasiveness and decreased the expression levels of vimentin. Wnt5a negativity was associated with poor tumor differentiation and positive vascular invasion, and was an independent poor prognostic factor in patients with HCC. Wnt5a may be a tumor suppressor involved in EMT-mediated changes in invasiveness.

Imaging Mass Spectrometry Reveals the Changes in the Taurine Conjugates of Dihydroxycholanoic Acid During Hepatic Warm Ischemia and Reperfusion in a Rat Model.

Warm ischemia and reperfusion injury (IRI) is a prognostic factor in donation after cardiac death donor transplantation. However, a reliable method to predict IRI before transplantation has not been established. The aim of this study was to identify predictive markers of hepatic IRI by simultaneous measurement of endogenous molecules using matrix-assisted laser desorption/ionization-imaging mass spectrometry (MALDI-IMS). Rats were subjected to hepatic warm ischemia (70%) for 30 or 90 minutes and subsequent reperfusion. The livers were collected at the end of ischemia and 1 hour, 6 hours, and 24 hours after reperfusion. The liver tissue sections were applied to IMS (m/z 200-2000). Candidate molecules were identified by tandem mass spectrometry. Imaging mass spectrometry (IMS) revealed a significant increase in the taurine conjugates of dihydroxycholanoic acid (TDHCA) during ischemia and a tendency to return to the basal level after reperfusion. Notably, high-resolution measurements revealed focal accumulation of TDHCA in the intrahepatic bile duct with ischemic time. In conclusion, IMS is a useful method to detect minute changes provoked by ischemia, which are barely detectable in assays involving homogenization. Accordingly, focal accumulation of TDHCA during ischemia may be a candidate marker for predicting later IRI.

Multi-omics analysis on an agroecosystem reveals the significant role of organic nitrogen to increase agricultural crop yield.

Both inorganic fertilizer inputs and crop yields have increased globally, with the concurrent increase in the pollution of water bodies due to nitrogen leaching from soils. Designing agroecosystems that are environmentally friendly is urgently required. Since agroecosystems are highly complex and consist of entangled webs of interactions between plants, microbes, and soils, identifying critical components in crop production remain elusive. To understand the network structure in agroecosystems engineered by several farming methods, including environmentally friendly soil solarization, we utilized a multiomics approach on a field planted with Brassica rapa We found that the soil solarization increased plant shoot biomass irrespective of the type of fertilizer applied. Our multiomics and integrated informatics revealed complex interactions in the agroecosystem showing multiple network modules represented by plant traits heterogeneously associated with soil metabolites, minerals, and microbes. Unexpectedly, we identified soil organic nitrogen induced by soil solarization as one of the key components to increase crop yield. A germ-free plant in vitro assay and a pot experiment using arable soils confirmed that specific organic nitrogen, namely alanine and choline, directly increased plant biomass by acting as a nitrogen source and a biologically active compound. Thus, our study provides evidence at the agroecosystem level that organic nitrogen plays a key role in plant growth.

Hepatectomy Combined with Diaphragmatic Resection for Hepatocellular Carcinoma with Diaphragmatic Involvement: A Propensity Score-Matched Analysis.

PURPOSE: We evaluated the short- and long-term surgical outcomes of hepatectomy combined with diaphragmatic resection for hepatocellular carcinoma (HCC) with diaphragmatic involvement. METHODS: We retrospectively reviewed the surgical outcomes of HCC patients with diaphragmatic resection (DR group) and HCC patients without diaphragmatic resection (non-DR group). We applied 1:1 propensity score matching (PSM) to these subjects. RESULTS: The study included 46 patients in DR group and 828 patients in non-DR group. The DR group cases were pathologically more advanced, and both overall and relapse-free survival among the patients in this group with pathological diaphragmatic invasion were similar to cases with pathological diaphragmatic fibrous adhesion. There were 40 patients from each group subjected to PSM. In these matched cohorts, there was no statistically significant difference between the two groups regarding perioperative outcomes, overall survival, and relapse-free survival. Multivariate analyses of our matched HCC patients revealed that alpha-fetoprotein expression and tumor size were independent prognostic factors for overall survival and poor differentiation for relapse-free survival, whereas neither diaphragmatic invasion nor diaphragmatic resection were prognostic indicators. The most frequent site of recurrence in non-DR group was the liver, whereas the most frequent site of recurrence in DR group was the lung before and after PSM. CONCLUSIONS: The short- and long-term surgical outcomes of DR HCC cases are equivalent to their non-DR counterparts under a matched clinicopathological background. Hepatectomy combined with DR is an acceptable treatment for HCC with either diaphragmatic fibrous adhesion or diaphragmatic invasion.

Heavy Water (D2O) Containing Preservation Solution Reduces Hepatic Cold Preservation and Reperfusion Injury in an Isolated Perfused Rat Liver (IPRL) Model.

BACKGROUND: Heavy water (D2O) has many biological effects due to the isotope effect of deuterium. We previously reported the efficacy of D2O containing solution (Dsol) in the cold preservation of rat hearts. Here, we evaluated whether Dsol reduced hepatic cold preservation and reperfusion injury. METHODS: Rat livers were subjected to 48-hour cold storage in University of Wisconsin (UW) solution or Dsol, and subsequently reperfused on an isolated perfused rat liver. Graft function, injury, perfusion kinetics, oxidative stress, and cytoskeletal integrity were assessed. RESULTS: In the UW group, severe ischemia and reperfusion injury (IRI) was shown by histopathology, higher liver enzymes leakage, portal resistance, and apoptotic index, oxygen consumption, less bile production, energy charge, and reduced glutathione (GSH)/oxidized glutathione (GSSG) ratio (versus control). The Dsol group showed that these injuries were significantly ameliorated (versus the UW group). Furthermore, cytoskeletal derangement was progressed in the UW group, as shown by less degradation of α-Fodrin and by the inactivation of the actin depolymerization pathway, whereas these changes were significantly suppressed in the Dsol group. CONCLUSION: Dsol reduced hepatic IRI after extended cold preservation and subsequent reperfusion. The protection was primarily due to the maintenance of mitochondrial function, cytoskeletal integrity, leading to limiting oxidative stress, apoptosis, and necrosis pathways.

Hepatocellular carcinoma producing granulocyte colony-stimulating factor: diagnosis and treatment.

Granulocyte colony-stimulating factor (G-CSF) is a naturally occurring glycoprotein that is synthesized by stromal cells in bone marrow. Several cases of G-CSF-producing malignant tumors in various organs have been reported, but it is extremely rare in hepatocellular carcinoma (HCC). Here, we report a rare case of HCC producing G-CSF. The patient presented with a continuous fever and had a huge liver mass in the right lobe with portal vein tumor thrombus (PVTT) in the right first branch. He had marked granulocytosis, and his serum level of G-CSF was elevated. A complete curative liver resection was performed after preoperative radiotherapy to PVTT. The pathological findings of the resected specimen revealed poorly/moderately differentiated HCC, and immunohistochemical staining of G-CSF was negative the first time it was tested, but the second time, it was positive in the cytoplasm of other tumor cells of HCC. Only a few cases of G-CSF-producing HCC have been reported, and they resulted in rapid tumor growth, metastases, and poor prognosis. In our case with PVTT, there was no liver recurrence, although multiple lung metastases occurred at 8 months after curative resection. We should consider G-CSF-producing HCC and diagnose promptly when encountering liver tumor patients with leukocytosis, and we should perform multimodal treatment including radiation, radical surgery, and chemotherapy.

Hepatic hypertrophy and hemodynamics of portal venous flow after percutaneous transhepatic portal embolization.

BACKGROUND: Percutaneous transhepatic portal embolization (PTPE) is useful for safe major hepatectomy. This study investigated the correlation between hepatic hypertrophy and hemodynamics of portal venous flow by ultrasound sonography after PTPE. METHODS: We analyzed 58 patients with PTPE, excluding those who underwent recanalization (n = 10). Using CT volumetry results 2 weeks after PTPE, the patients were stratified into a considerable hypertrophy group (CH; n = 15) with an increase rate of remnant liver volume (IR-RLV) ≥ 40% and a minimal hypertrophy group (MH; n = 33) with an IR-RLV < 40%. We investigated the hemodynamics of portal venous flow after PTPE and the favorable factors for hepatic hypertrophy. RESULTS: Univariate and multivariate analysis identified the indocyanine green retention rate at 15 min (ICGR15) and increase rate of portal venous flow volume (IR-pFV) at the non-embolized lobe on day 3 after PTPE as independent favorable factors of IR-RLV. Patients with IR-pFV on day 3 after PTPE ≥100% and ICGR15 ≤ 15% (n = 13) exhibited significantly increased IR-RLV compared with others (n = 35). CONCLUSIONS: Cases with high IR-pFV on day 3 after PTPE exhibited better hepatic hypertrophy. Preserved liver function and increased portal venous flow on day 3 were important.

Optimal resection area for superior mesenteric artery nerve plexuses after neoadjuvant chemoradiotherapy for locally advanced pancreatic carcinoma.

Recently, several reports demonstrated the efficacy of neoadjuvant chemotherapy (NAC) or chemoradiotherapy (NACRT) for patients with borderline resectable (BRPC) and locally advanced unresectable pancreatic carcinoma (LAPC). The aim of this study was to evaluate the treatment response after NACRT, especially for nerve plexuses, and the optimal resection area for superior mesenteric artery nerve plexuses in BRPC and LAPC patients after NACRT.A total of 17 patients with BRPC and LAPC received preoperative gemcitabine-based NACRT. The numbers of BRPC and LAPC patients were 13 and 4, respectively. We evaluated nerve plexus invasion by CT before and after NACRT, decided on the resection area of plexus invasion in SMA before NACRT, and compared the preoperative evaluation and clinicopathological findings.In the plexus of the supra-mesenteric artery (pl-SMA), arterial nerve plexus invasion, in cases <90°, all patients showed the absence of residual cancer in the resected specimen after NACRT. In cases between 90° and 180°, 1 of 2 patients (50%) showed nerve plexus invasion. In cases over 180°, all patients showed nerve plexus invasion. We could perform R0 resection in all 10 cases, and pl-SMA invasion disappeared in 6 of 7 BRPC patients.We demonstrated the relationship between the angle of nerve plexus tumor invasion and treatment effect after NACRT. We could perform R0 resection in all pl-SMA invasion cases, deciding on the resection area of pl-SMA based on CT before NACRT.

R0 Resection for Locally Advanced Pancreatic Cancer with Low-dose Gemcitabine with Wide Irradiation Area as Neoadjuvant Chemoradiotherapy.

BACKGROUND: Local antitumor efficacy and the outcome of neoadjuvant chemoradiotherapy (NACRT) with low-dose gemcitabine and wide irradiation area for borderline resectable and unresectable pancreatic cancer were evaluated. PATIENTS AND METHODS: Thirty-four cases of borderline resectable and unresectable pancreatic cancer were recruited. Three-dimensional conformal radiotherapy to the pancreatic bed and the region scheduled for lymph node dissection was performed to a total dose of 50.4 Gy28 fractions with gemcitabine at a dose of 150 mg/m2 weekly. Clinical and pathological results were examined. RESULTS: Twenty-seven patients (79.4%) completed the protocol. Grade 3/4 leucopenia (n=10), and grade 3 anorexia (n=1) occurred. Seven cases were excluded (two refused treatment; five had progressive disease), 20 underwent laparotomy, and 16 resected (47.1%) cases achieved R0 resection. Median survival time, and 3-year and 5-year survival rates were 39.0 months, and 56.3% and 28.1% in resected cases, respectively. CONCLUSION: NACRT with low-dose gemcitabine and wide irradiation area achieved 100% R0 resection and acceptable prognosis.

Impact of tumor localization on the outcomes of surgery for an intrahepatic cholangiocarcinoma.

BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) shows differing clinical outcomes depending on its localization. METHODS: We reviewed the surgical outcomes of 104 ICC patients who underwent liver resection at our institution. We divided ICC into hilar type (HICC) and peripheral type (PICC) depending on positive contact with the hepatic hilum on preoperative computed tomography (CT). RESULTS: The survival outcomes were significantly poorer in HICC patients. HICCs showed a larger tumor size and more frequent bile duct invasion, lymph node metastasis, and non-curative resection than PICC. Resections for HICC had greater blood loss and required a longer operation time, larger hepatectomy, and more frequent extrahepatic bile duct resection. HICCs, even if small in size, also showed a greater tendency to metastasize to the lymph nodes of the hepatoduodenal ligament. Univariate analysis of the ICCs in our current cohort revealed that tumor size, multiple tumors, bile duct invasion, lymph node metastasis, non-curative resection, and HICC are associated with a poorer overall survival outcome. Multivariate analysis indicated that multiple tumors and non-curative resection were independent prognostic factors for survival. Among the curative resection cases, however, survival did not differ significantly between HICC and PICC. The accuracy rate of our CT-based classification for the pathological classification was 81.7%. CONCLUSIONS: HICC shows more frequent bile duct invasion and lymph node metastasis, requires more extensive surgery, and has a higher rate of non-curative resection than PICC. However, if curative resection is achieved, the survival outcomes are expected to be equivalent between HICC and PICC.

Pancreaticoduodenectomy with Preservation of Collateral Circulation or Revascularization for Biliary Pancreatic Cancer with Celiac Axis Occlusion: A Report of 2 Cases.

BACKGROUND In cases of celiac axis occlusion requiring pancreaticoduodenectomy for malignancy, both oncologic curability and control of hepatic arterial flow must be considered, but the operative strategy is undeveloped. CASE REPORT Case 1: A 74-year-old man was diagnosed with hilar cholangiocarcinoma with celiac axis stenosis. The collateral from the superior mesenteric artery ran through the pancreas head but no invasion was observed in preoperative imaging. Hepatopancreatoduodenectomy with preservation of a collateral was performed. Case 2: A 69-year-old woman was diagnosed with pancreas head cancer with celiac axis occlusion. The collateral from the superior mesenteric artery ran through pancreas head and tumor invasion was observed. Pancreaticoduodenectomy with bypass revascularization using a vein graft was performed. Both operations were performed safely oncologically under preoperative planning that was based on computed tomographic angiography. The operative procedure was ultimately determined by evaluation of perioperative blood flow under Doppler ultrasonography after clamping the gastroduodenal artery. CONCLUSIONS Preoperative simulations of arterial revascularization and perioperative evaluation of blood flow are necessary for the success of this procedure.

[A Case of Locally Advanced Intrahepatic Cholangiocarcinoma Successfully Treated by Conversion Surgery after Hepatic Arterial Infusion Chemotherapy and Radiation Therapy].

The patient was a 63-year-old man. Computed tomography(CT)showed a 99mm in diameter low-density mass in hepatic segments 4 and 8 as the main locus. This tumor was diagnosed as intrahepatic cholangiocarcinoma and was suspected to invade to left and right Gleason's sheath, and radical cure was judged impossible. After hepatic arterial chemotherapy and radiotherapy were performed, tumor shrinkage was confirmed, and tumor markers also became negative. So he was referred to our hospital for surgical indication. CT revealed that the tumor did not invade to the left Gleason's sheath. After percutaneous transhepatic portal embolization, hepatic right trisectionectomy was performed. He was administered gemcitabine as an adjuvant chemotherapy for 1 year. One year 5 months after surgery, the patient is alive without relapse. Preoperative hepatic arterial chemotherapy and radiotherapy could be an effective treatment for unresectable locally advanced intrahepatic cholangiocarcinoma.

Curative resection of pancreatic ductal adenocarcinoma developing in the remnant pancreas 13 years after distal pancreatectomy for intraductal papillary mucinous neoplasms: A case report.

Intraductal papillary mucinous neoplasms (IPMNs) are characterized by the papillary proliferation of atypical mucinous epithelial cells in the pancreatic ductal system. There are two recurrence patterns following resection of IPMNs: Metachronous multifocal occurrence of IPMNs, and distinct pancreatic ductal adenocarcinoma (PDAC) in the remnant pancreas. Several recent studies investigated the development of distinct PDAC during follow-up evaluation of IPMNs and the incidence rate ranged from 4.5 to 8%. Thus, IMPNs may be a good predictor for the early detection of PDAC during observation or after the resection of IPMNs. We herein report the rare case of a patient who underwent resection of PDAC that developed in the remnant pancreas 13 years after distal pancreatectomy with splenectomy for IPMNs. PDAC may develop in the remnant pancreas after pancreatectomy for IPMNs; thus, careful long-term follow-up with periodic surveillance, at least every 6 months, is warranted.

Transparenchymal glissonean approach: a novel surgical technique for advanced perihilar bile duct cancer.

PURPOSE: To increase the surgical opportunities for locally advanced perihilar bile duct cancers that require left-sided hepatectomies, we developed the transparenchymal glissonean approach (TGA); it comprises intra-hepatic exposure and dissection of the Glisson's sheath to gain access to the hepatic artery and portal vein for reconstruction. METHODS: Following skeletonization of the hepatoduodenal ligament, the proximal portions of invaded vessels are exposed. If extra-hepatic attempts to access the distal portions of the invaded vessels fail, TGA can be used. The distal portion of the invaded right or right posterior Glisson's sheath is exposed following liver transection. The anterior portion of the wall of bile duct is cut and transected circumferentially including the fibrous plate tissue. The non-invaded portal vein and hepatic artery are isolated and dissected towards the hepatic hilum until the invaded distal portion of the vessels, and vascular reconstructions are performed. RESULTS: TGA was performed in 9 patients; 5 patients underwent left hemihepatectomy and 4 underwent left tri-sectionectomy. Eight patients needed vascular reconstruction. Clavien-Dindo classification (CDC) grades IIIa and IIIb were recorded in 6 and 1 patients, respectively. No patients had CDC grades IV and V disease. Pathologically, all cases were pT4; 3 cases were R0, 5 were R1 with microscopic positive margin, and 2 were R1 with microscopic metastasis. The overall median survival time was 25.0 months. CONCLUSIONS: TGA is feasible with acceptable prognosis and expands the surgical opportunities.

Salvage Hepatectomy for Recurrent Hepatocellular Carcinoma after Radiofrequency Ablation and/or Transcatheter Arterial Chemoembolization: A Propensity Score-Matched Analysis.

AIM: We aimed to evaluate the short- and long-term surgical outcomes of salvage hepatectomy for recurrent hepatocellular carcinoma (HCC) after radiofrequency ablation (RFA) and/or transcatheter arterial chemoembolization (TACE). METHODS: We reviewed the surgical outcomes of 90 recurrent HCC patients after RFA and/or TACE (salvage group) and 490 HCC patients without preoperative treatment (primary group). We performed 1:1 propensity score matching (PSM) between the 2 groups and matched 87 patients in each group. RESULTS: Before PSM, the salvage group was pathologically more advanced than the primary group. After PSM, there were no significant differences in the clinicopathological features between the groups. The outcomes of propensity score-matched groups were compared and there was no statistically significant difference between the 2 groups regarding perioperative outcomes and survival. Univariate and multivariate analyses of propensity score-matched HCC patients revealed that stage, tumor size, differentiation, and portal vein invasion were independent prognostic factors for survival. Preoperative RFA and/or TACE was not a prognostic factor in a propensity score-matched cohort. CONCLUSIONS: The short- and long-term surgical outcomes of the primary and salvage groups were similar under the matched clinicopathological background. Salvage hepatectomy might be an acceptable treatment for recurrent HCC patients after RFA and/or TACE.

Survival outcomes of hepatectomy for stage B Hepatocellular carcinoma in the BCLC classification.

BACKGROUND: Because hepatectomy is not recommended in patients with stage B hepatocellular carcinoma (HCC) of the Barcelona Clinic Liver Cancer (BCLC) staging, we evaluated the survival outcomes of hepatectomy for stage B in the BCLC system. METHODS: Data were collected from 297 consecutive adult stage B patients who underwent curative hepatectomy for HCC between 1996 and 2014 in Hokkaido University Hospital. Overall survival (OS), disease-free survival (DFS), and risk factors were analyzed using the Kaplan-Meier method. Independent prognostic factors were evaluated using a Cox proportional hazards regression model. AP-factor (alpha-fetoprotein [AFP] × protein induced by vitamin K absence or antagonism factor II [PIVKA-II]) was categorized according to the serum concentrations of AFP and PIVKA-II: AP1 (AFP < 200 ng/ml and PIVKA-II < 100 mAU/ml), AP2 (AFP × PIVKA-II < 105), and AP3 (AFP × PIVKA-II ≥ 105). RESULTS: There were 130 deaths among our 297 stage B patients (43.8%). The causes of death in these cases were HCC recurrence (n = 106; 81.5%), liver failure (n = 7; 5.4%), and other causes (n = 17; 16.1%). The operative mortality rate was 0.34% (1/297). The 5-year OS and DFS rates for the stage B cases were 54.3 and 21.9%, respectively. By multivariate analysis, tumor number and AP-factor were risk factors for both survival and recurrence that were tumor related and could be evaluated preoperatively. The study patients with stage B HCC were classified into three groups by tumor number (B1, 1; B23, 2 or 3; B4over: ≥4) and into three groups stratified by AP-factor (AP1, AP2, and AP3). The 5-year OS rates of B1, B23, and B4over were 63.6, 52.3, and 29.0%. The 5-year OS rates of AP1, AP2, and AP3 were 67.6, 65.2, and 39.1%. Stratified by the 5-year OS rate, stage B HCC patients were classified into three subgroups (A-C).The 5-year OS rates of groups A (B1 or B23 and AP-1 or AP-2), B (B1 or B23 and AP-3, or B4over and AP-1 or AP-2), and C (B4over and AP-3) were 69.5, 43.7, and 21.3%. CONCLUSION: Stage B HCC patients with a tumor number ≤ 3 and/or AP-factor < 1 × 105 show acceptable 5-year OS rates and could be treated by hepatectomy.

Fatty acid-binding protein 5 function in hepatocellular carcinoma through induction of epithelial-mesenchymal transition.

Hepatocellular carcinoma (HCC) is a highly prevalent cancer with poor prognosis. The correlation between overexpression of fatty acid-binding protein 5 (FABP5) and malignant potential of tumor growth and metastasis in several cancers has been previously reported. However, the correlation between FABP5 expression and HCC malignant behavior remains unknown. We compared FABP5 expression and patient characteristics in paired HCC and adjacent noncancerous liver tissues from 243 patients who underwent surgical resection of primary HCC. Cell proliferation, invasion, and migration assays were performed in HCC cell lines overexpressing FABP5 or downregulated for FABP5. Tumor growths were monitored in xenograft model, and liver and lung metastasis models were established. In the 243 HCC patients, FABP5-positive staining (n = 139/243, 57.2%) was associated with poor prognosis and recurrence (P < 0.0001) and showed positive correlation with distant metastasis, tumor size and vascular invasion (P < 0.05). Cell proliferation, invasion, and migration in vitro were enhanced by upregulation of FABP5 and decreased by downregulation of FABP5 in HCC cell lines. Similar results in tumor formation and metastasis were obtained through in vivo analyses. PCR array results revealed upregulation of SNAI1 in FABP5-overexpressing HepG2 cells. Western blot analysis showed significantly increased expression of E-cadherin and ZO-1 and decreased SNAI1 expression and nuclear translocation of ß-catenin by knockdown of FABP5. We revealed a significant role for FABP5 in HCC progression and metastasis through the induction of epithelial-to-mesenchymal transition. FABP5 may be a potential novel prognostic biomarker and new therapeutic target for HCC.