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BACKGROUND The prognosis of advanced hepatocellular carcinoma (HCC) that is not indicated for curative hepatectomy remains poor, despite advances in the treatment of HCC, including the development of tyrosine kinase inhibitors (TKIs). The outcomes of reduction hepatectomy and multidisciplinary postoperative treatment for advanced HCC that is not indicated for curative hepatectomy, including those of recently treated cases, should be investigated. AIM To examine the outcomes of combination treatment with reduction hepatectomy and multidisciplinary postoperative treatment for advanced HCC that is not indicated for curative hepatectomy. METHODS Thirty cases of advanced HCC that were not indicated for curative hepatectomy, in which reduction hepatectomy was performed between 2000 and 2018 at the Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, were divided into postoperative complete remission (POCR) (+) and POCR (-) groups, depending on whether POCR of all evaluable lesions was achieved through postoperative treatment. The cases in the POCR (-) group were subdivided into POCR (-) TKI (+) and POCR (-) TKI (-) groups, depending on whether TKIs were administered postoperatively. RESULTS The 5-year overall survival rate and mean survival time (MST) after reduction hepatectomy were 15.7% and 28.40 mo, respectively, for all cases; 37.5% and 56.55 mo, respectively, in the POCR (+) group; and 6.3% and 14.84 mo, respectively, in the POCR (-) group (P = 0.0041). Tumor size, major vascular invasion, and the number of tumors in the remnant liver after the reduction hepatectomy were also found to be related to survival outcomes. The number of tumors in the remnant liver was the only factor that differed significantly between the POCR (+) and POCR (-) groups, and POCR was achieved significantly more frequently when & LE; 3 tumors remained in the remnant liver (P = 0.0025). The MST was 33.52 mo in the POCR (-) TKI (+) group, which was superior to the MST of 10.74 mo seen in the POCR (-) TKI (-) group (P = 0.0473). CONCLUSION Reduction hepatectomy combined with multidisciplinary postoperative treatment for unresectable advanced HCC that was not indicated for curative hepatectomy was effective when POCR was achieved via multidisciplinary postoperative therapy. To achieve POCR, reduction hepatectomy should aim to ensure that & LE; 3 tumors remain in the remnant liver. Even in cases in which POCR is not achieved, combined treatment with reduction hepatectomy and multidisciplinary therapy can improve survival outcomes when TKIs are administered.

The N‑glycoforms of glycoproteins modify protein function and control a number of biological pathways. The aim of the present study was to investigate the correlation between alterations in N‑glycans and cancer aggressiveness in terms of cancer cell invasion ability. The expression of urokinase‑type plasminogen activator (uPA) and N‑acetylglucosaminyltransferase V (GnT‑V) in liver cancer cell lines was analyzed by western blotting. Cell invasiveness was analyzed by Matrigel invasion assays. uPA and GnT‑V expression in liver cancer cell lines was knocked down by RNA interference. Furthermore, uPA was overexpressed in liver cancer cells using lentiviral vectors, and a mutant strain of HepG2 cells overexpressing uPA deficient in N‑glycans was established. A glycoblotting‑assisted matrix‑assisted laser desorption/ionization‑time‑of‑flight/mass spectrometry‑based quantitative analysis of liver cancer cell lines was performed, in which invasiveness was altered by modifying the expression of uPA and GnT‑V. N‑glycan profiles were found to differ between the highly invasive liver cancer cell line HLE and the less invasive cell line HepG2. The expression of several N‑glycans, including a form with m/z=1892, was changed according to invasiveness controlled by knockdown and overexpression of uPA. The invasiveness of HepG2 cells with mutant uPA did not increase regardless of the level of expression of uPA. Following GnT‑V knockdown and N‑glycan alteration, uPA expression did not change, whereas cell invasiveness decreased. One N‑glycan (m/z=1892) was common among N‑glycans in the comparative analysis between HLE and HepG2, HLE and uPA knockdown HLE, HepG2 and uPA‑overexpressing HepG2, and HLE and GnT‑V knockdown HLE cells and among N‑glycan profiles in human uPA. Therefore, N‑glycosylation is an important factor controlling invasiveness of liver cancer cells, and a specific N‑glycan (m/z=1892) associated with the invasion of liver cancer cells via uPA was identified in the present study.

A single hepatocellular carcinoma (HCC) is a good indication for hepatic resection regardless of tumor size, but the surgical indications for cases with multiple HCCs remain unclear.We retrospectively reviewed the outcomes of hepatectomies for Barcelona Clinic Liver Cancer (BCLC) stage 0, A, and B HCCs. We further subclassified stage A and B into A1 (single nodule5 cm, or three or fewer nodules ≤3 cm), A2 (single nodule 5-10 cm), A3 (single nodule ≥10 cm), B1 (two to three nodules3 cm), and B2 (four or more nodules).A total of 1088 patients were enrolled, comprising 88 stage 0, 750 stage A (A1: 485; A2: 190; A3: 75), and 250 stage B (B1: 166; B2: 84) cases. The 5-year overall survival (OS) rates for stage 0, A1, A2, A3, B1, and B2 patients were 70.4%, 74.2%, 63.8%, 47.7%, 47.5%, and 31.9%, respectively (p 0.0001). Significant differences in OS were found between stages A1 and A2 (p = 0.0118), A2 and A3 (p = 0.0013), and B1 and B2 (p = 0.0050), but not between stages A3 and B1 (p = 0.4742). In stage B1 patients, multivariate analysis indicated that Child-Pugh B cirrhosis was the only independent prognostic factor for the OS outcome.A hepatectomy should be considered for multiple HCCs if the number of tumors is three or fewer, especially in patients with no cirrhosis or in Child-Pugh A cases, because the long-term results are equivalent to those for a single HCC.

This study was performed to determine the clinical significance of adenomatous polyposis coli (APC)-binding protein end-binding 1 (EB1) in hepatocellular carcinoma (HCC) and to characterize its biochemical role in comparison with previous reports. We performed immunohistochemical staining to detect EB1 expression in tissues from 235 patients with HCC and investigated its correlations with clinicopathological features and prognosis. We also investigated the roles of EB1 in cell proliferation, migration, and tumorigenesis in vitro and in vivo by siRNA- and CRISPR/Cas9-mediated modulation of EB1 expression in human HCC cell lines. The results showed that EB1 expression was significantly correlated with several important factors associated with tumor malignancy, including histological differentiation, portal vein invasion status, and intrahepatic metastasis. Patients with high EB1 expression in HCC tissue had poorer overall survival and higher recurrence rates than patients with low EB1 expression. EB1 knockdown and knockout in HCC cells reduced cell proliferation, migration, and invasion in vitro and inhibited tumor growth in vivo. Further, genes encoding Dlk1, HAMP, and SLCO1B3 that were differentially expressed in association with EB1 were identified using RNA microarray analysis. In conclusion, elevated expression of EB1 promotes tumor growth and metastasis of HCC. EB1 may serve as a new biomarker for HCC, and genes coexpressed with EB1 may represent potential targets for therapy.

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 beta-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.

症例は59歳，女性．1983年10月右顎下部の疼痛を主訴に近医を受診し，右顎下腺癌の診断で1984年3月右顎下腺摘出術を施行した．病理組織診断は腺様嚢胞癌であった．以後，再発なく経過したが，2006年2月左頭頂部に腫瘤を認めた．顎下腺癌骨転移が疑われ，脳神経外科専門病院にて転移巣を切除した．病理組織診断は顎下腺癌の頭頂骨転移であった．2008年4月18F-fluorodeoxy glucose-positron emission tomographyにて肝に複数の集積像を認め，5月当科を紹介受診した．右葉を中心とした顎下腺癌の両葉多発肝転移と診断し，Percutaneous transhepatic portal vein embolization後7月17日に拡大肝右葉切除+尾状葉切除+肝部分切除（S3），また，残肝深部にあったS2/3転移巣は超音波ガイド下Microwave coagulation therapyを施行し，すべての転移巣を処理した．病理組織診断は顎下腺腺様嚢胞癌の肝転移であった．20年以上の長期無再発経過の後，多発肝転移をきたした顎下腺癌の1例を経験したので，文献的考察を加えて報告する．

We report a rare case of clear cell sarcoma of the esophagus and review the literature regarding clear cell sarcomas of the gastrointestinal tract. A 57-year-old male was admitted with dysphagia during swallowing. Preoperative imaging studies, including upper gastrointestinal endoscopy and endoscopic ultrasonography, showed that the tumor was located between the mucosa and the muscularis propria of the lower esophagus. We performed subtotal esophagectomy with gastric tube reconstruction. Pathological findings of the tumor showed mixed spindle cells and oval cells. Immunohistochemical staining showed that the tumor cells were positive for S-100, vimentin and neuron-specific enolase and negative for α-smooth muscle actin, myoglobin and c-kit. Fluorescence in situ hybridization using a Ewing sarcoma breakpoint region 1 probe showed split signals in a small percentage of cells. We finally diagnosed the patient with clear cell sarcoma of the esophagus.

For aging, people having malignant disease are increasing. And surgical resection is an important part in the treatment of pulmonary metastasis from colorectal cancer. We analyzed the treatment outcome and prognostic factors affecting survival in our subset of patients. We have experienced 64 operations of metastatic lung tumors from colorectal cancer for 23 years since January 1988. Various factors affecting prognosis are studied based on 5-year survival in this report. Overall 5-year survival rate was 38.7%. The disease-free intervals more than 2 years, a solitary metastatic pulmonary lesion and the serum level of prethoracotomy carcinoembryonic antigen (CEA) were significantly affecting factors on the prognosis. Furthermore, sequential study for 23 years couldn't demonstrate the prognostic improvement by the advance of the thoracoscopic technology or the development of the new anti-cancer drugs, though the treatment of patients with pulmonary metastases from colorectal cancer continues to evolve. The role of pulmonary metastasectomy is very important to reduce the volume of metastatic lesions for the better prognosis.

Pleomorphic carcinoma is rare in the primary lung cancer with a poor prognosis. We reported a resected case of pleomorphic carcinoma of the lung with rapid progression. A 62-year-old male with a tumor shadow in the right lung which had not been noted 9 months before was referred to our hospital. The abnormal shadow was not noted 9 months ago. The tumor located in the right lower lobe and rapidly enlarged from 7.5 cm to 9.5 cm in a month. Right pneumonectomy was necessary, because of the intrapulmonary metastasis in the right upper lobe. Pathological findings showing spindle cells with massive necrosis, were consistent with a diagnosis of pleomorphic carcinoma. Only by 45 days after operation, local recurrence and metastases to the brain, right adrenal gland and small intestine were found, resulting in death at 67 days after operation.

Circumportal pancreas (CP) is an extremely rare pancreatic fusion anomaly which is usually asymptomatic. This report presents the case of a patient with a tumor in the head of a CP and the retroportal accessory pancreatic duct in the pancreatic tissue behind the portal vein. A 53-year-old male was diagnosed with a nonfunctioning neuroendocrine tumor of the pancreas and resection of the tumor was scheduled. The patient was revealed to have CP on preoperative computed tomography and endoscopic retrograde cholangiopancreatography, which showed the pancreatic tissue encircling the portal vein and the retroportal accessory pancreatic duct. The patient safely underwent pylorus-preserving pancreatoduodenectomy reconstructed with pancreaticogastrostomy.

We report two cases of neuroendocrine carcinoma of the rectum. CASE 1: A 50s woman was diagnosed as rectal cancer and underwent anterior resection of the rectum and lymphnode dissection. The histological diagnosis was neuroendocrine carcinoma with peritoneal dissemination. She was treated with chemotherapy as an outpatient. One year later from the operation, multiple liver metastases were revealed and she died eight months later. CASE 2: A 50s man underwent endoscopic mucosal resection (EMR) of the rectum as rectal tumor and histological diagnosis was an early well-moderate deferenciated carcinoma and its cut-tend was unclear. He received a careful follow-up. One year later, a follow-up colonoscopy revealed a submucosal tumor in the lower rectum. He was diagnosised with local reccurence of rectal cancer, and then underwent an abdominoperineal resection of the rectum and lymphnode dissection. The histological diagnosis was poorly differenciated neuroendocrine carcinoma with lymphnode metastasis. Two months later from the operation, a local reccurence was revealed and he was treated with octreotide and irradiation.

A 60s male was admitted to our hospital for a diagnosis of gastric tumor sized 20 mm in diameter at the fornix of the stomach. Endoscopic mucosal resection (EMR) was performed, and the resected tumor was pap, m, ly0, v0, HMX, VM0, pathologically. One month after the EMR, the local recurrence was confirmed and a partial gastrectomy was performed. Pathological findings were tub1, sm2, ly1, v1, HM0, VM0. Total gastrectomy was added because of the possibility of the lymph node metastasis. Pathological findings revealed no residual cancers. The final pathological diagnosis was T1b(sm2) N0H0P0M0, Stage IA, based on the Japanese classification of gastric cancer. Three months thereafter, CT showed multiple liver metastases. Immunohistochemical study of the operated tumor revealed AFP-producing gastric cancer. Chemotherapy was performed, but he died of the gastric cancer. Endoscopic treatment is a minimally invasive therapeutic strategy, but it requires a considerable care in application.

Treatment for hepatocellular carcinoma (HCC) with advanced cirrhosis, especially with hypersplenic thrombocytopenia, will be very difficult. Then we evaluated usefulness of concomitant splenectomy with treatment for patients with HCC, severe cirrhosis and huge splenomegaly. The preoperative mean platelet (Plt) count was 4.6 × 10(4)/µL and the mean longest diameter of spleen on CT was 143.0 mm. The mean Plt count on postoperative days 14 and 28 was 23.1 × 10(4)/µL (p=0.005) and 16.1 × 10(4)/µL (p=0.01), respectively and improved significantly compared with preoperative one. A white blood cell count and serum albumin also improved significantly on postoperative days 14 and 28, respectively. Treatment for recurrent HCC after splenectomy was preformed 2.4 times per patient (transarterial chemoembolization 13 times and radiofrequency ablation 4 times/7 patients). Now 5 patients are alive and the mean survival period was 17.3 months (range 8-38 months). It maybe said that concomitant splenectomy for cirrhotic patients with HCC and huge splenomegaly who need to receive a treatment for HCC was useful in our study, because those patients could receive a treatment for recurrent HCC repeatedly, and that probably contributes to the improvement of prognosis.

310 Background: Hepatocellular carcinoma (HCC) is one of the cancer types with poor prognosis. The high expression of Fatty Acid Binding Protein 5 (FABP5) has been reported its malignant potential in several cancers. However, the function of FABP5 in HCC remains unknown. We analyzed the correlation between the expression of FABP5 and malignant behavior of HCC using HCC tissues and human HCC cell lines. Methods: A total of 231 HCC samples were obtained through our institute and subjected to immunohistochemical analysis. In vitro, protein expression of FABP5 in HCC cell lines was assessed by Western blot analysis. To the higher FABP5 expression cell lines, we performed proliferation assay, migration assay and invasion assay with or without genetic down-regulation of FABP5 by short hairpin RNA (shRNA). Results: The intensity of immunostaining in HCC tissues was determined comparing to immunoreactivity of Kupffer cells, and the patients were divided into a strong staining group (n=127) and a weak staining group (n=104) according to the intensity of immunostaining. In the strong staining group, 5-year overall survival rate was 58.3%, compared with 90.5% in the weak staining group (p