Hiroaki Nagano

Background and Aim: To dissect the high rate of non‐curative resection associated with biliary tract caner, we compared the outcome of non‐curative resection with that of inoperable cancer in patients referred for surgery.Methods: We retrospectively analyzed 447 patients with biliary tract cancer who were referred to our hospital between 1970 and 2008. We compared the background and overall survival (OS) rates accordingly to surgery (curative resection, non‐curative resection, or no surgery “inoperable”) and alternative therapies (chemotherapy and/or radiotherapy).Results: The 3‐year OS rate was 19% for the non‐curative resection group (n = 72) and 2% for the inoperable group (n = 135, P < 0.0001). Among the inoperable cases, the 3‐year OS rate for patient who received chemotherapy, including gemcitabine (GEM), was 18% (n = 18), which was similar to that of patients of the non‐curative resection who were treated with GEM (P = 0.7379). There were no significant differences in survival between non‐curative resection without GEM and inoperable cases with GEM‐based chemotherapy.Conclusion: Our results indicate that the prognosis of patients who undergo non‐curative surgery is better than those with inoperable cancer, but similar to those who receive chemotherapy including GEM. J. Surg. Oncol. 2011; 104:499–503.

Insulin‐like growth factor‐binding protein 7 (IGFBP7) functions in several cellular processes including proliferation, senescence and apoptosis. This study analyzed IGFBP7 function in hepatocellular carcinoma (HCC) cells by gene manipulation and investigated the prognostic significance of IGFBP7 expression in clinical HCC samples. In this study, we investigated changes in malignant potential such as cell growth and invasiveness in an HCC cell line, PLC/PRF/5, after transfection with shRNA against IGFBP7. The extent of apoptosis and cell cycle progression were examined after the transfection. The correlation between immunohistochemically determined IGFBP7 expression and long‐term postoperative prognosis after curative resection was also investigated in clinical HCC specimens obtained from 104 patients. PLC/PRF/5 cells transfected with shRNA against IGFBP7 showed significantly more rapid growth and stronger invasiveness than control cells. Annexin V assays showed that the IGFBP7‐depleted cells were significantly more resistant to apoptosis than the control cells, and showed decreased expression of cleaved caspase‐3 and PARP. Cell cycle progression was more rapid in the IGFBP7‐suppressed cells. In clinical HCC specimens, IGFBP7 expression was judged as positive in 67 patients (64.4%) and negative in the remaining 37 patients (35.6%). The IGFBP7 downregulation correlated significantly with poor postoperative prognosis, and IGFBP7 status was identified as an independent significant prognostic factor. Our results indicated that IGFBP7 expression correlated significantly with the malignant potential in HCC cells, suggesting that the expression could be a useful prognostic marker for HCC.

Background and Objectives: Histopathologically confirmed lymph node metastasis is a prognostic factor in the surgical treatment of biliary tract cancer, however, preoperative diagnosis is still difficult even with computed tomography. FDG‐PET has been used for the diagnosis of cancer and metastatic lesions. Herein, we retrospectively evaluated the utility of FDG‐PET for detection of lymph node metastasis in biliary tract cancer.Methods: We measured SUV_max at each 190 surgically dissected lymph node area in 36 patients, and compared the values with histopathological diagnosis. The cutoff values for SUV_max were defined from the ROC curve and the mean plus two standard deviations then used for detection of metastatic lymph node and prognostic value, compared with CT diagnosis.Results: The sensitivity, specificity, and positive predictive value of FDG‐PET were better than CT diagnosis (86%, 74%, 43% for SUV_max ≥ 2.0, and 37%, 97%, 72% for SUV_max ≥ 2.8, respectively). There was no relationship between SUV_max and CT‐determined lymph node dimensions. The presence of SUV_max ≥ 2.8 lymph nodes was an independent determinant of prognosis after surgical treatment.Conclusion: The detection of metastatic lymph nodes by FDG‐PET is limited, but better than CT. SUV_max for lymph nodes seems useful for clinical decision‐making regarding treatment strategy including surgery. J. Surg. Oncol. 2011; 103:223–229.

Background and Objectives Interferon (IFN) can eradicate hepatitis C virus (HCV)‐RNA from serum and hepatic tissue, and suppress the development of hepatocellular carcinoma (HCC). Despite such effectiveness, HCC develops even in HCV patients successfully treated with IFN therapy. Methods HCV‐related HCC patients who underwent curative hepatectomy for HCC were divided into three groups according to preceding IFN for HCV infection therapy and the therapeutic effect: responders group (n = 23), non‐responders group (n = 46), and no‐IFN group (n = 215). Postoperative outcome was retrospectively examined in the three groups. Results AST and ALT were significantly lower in responders group than non‐responders group (P < 0.001, P = 0.001) and no‐IFN group (P = 0.001, P = 0.002). Platelet count was significantly higher in responders group than other groups (P = 0.008, P = 0.001). The percentage of cirrhotic patients in responders group was significantly lower than other groups (P = 0.017, P = 0.014). Multivariate analysis identified preceding IFN therapy to be associated with disease‐free survival at marginal significance (P = 0.086), and as a significant independent factor for overall survival (P = 0.042). Conclusions Preceding IFN therapy for HCV infection improves postoperative outcome in HCV‐related HCC patients treated successfully with IFN. J. Surg. Oncol. 2010;102:308–314.

Previously, we reported guanylate-binding protein 2 (GBP2) and interferon regulatory factor 1 (IRF1) elevated in the rat peripheral blood during acute cellular rejection (ACR), which are identified from transcriptome analysis of liver graft, as leukocyte-related gene in liver. In this study, we investigated whether these two genes could differentially diagnose ACR from other types of liver dysfunction (LD) clinically. The mRNAs from leukocytes of 19 patients with ACR and 27 with LD, as well as from liver biopsies of 12 patients with ACR and 12 with LD, were analysed by real-time PCR for GBP2 and IRF1 expression. Sensitivity and specificity were calculated using receiver operator characteristic (ROC) curves. Guanylate-binding protein 2 (GBP2) and interferon regulatory factor 1 (IRF1) gene expression levels in ACR samples were higher than that in controls, and GBP2 expression in blood was higher than that in LD (26.4 +/- 3.1 and 15.6 +/- 1.9, P = 0.0203). Multivariate analysis showed that the ratio GBP2/glyceraldehyde-3-phosphate dehydrogenase (GAPDH) was independent of ACR-related factors (OR = 0.911, P = 0.035). GBP2 expression levels in ACR were also higher than that in liver transplantation patients with hepatitis C or no LD. Using a cut-off value of 20, the sensitivity and specificity of GBP2/GAPDH based on ROC curve analysis were 63% and 85% respectively. GBP2 in the patients with LD may be useful for diagnosis of ACR.

Background: Preoperative prognostic information to select a treatment strategy is important especially in patients who need highly aggressive surgery, such as those with biliary cancer. We evaluated various prognostic factors and non‐curative surgical factors using multidetector computed tomography (MDCT).Methods: We retrospectively analyzed 71 patients who underwent MDCT preoperatively and were scheduled for surgical resection of biliary cancer. For MDCT diagnosis, we used MDCT‐based classification equivalent to the surgical and pathological classification of the Japanese Society of Biliary Surgery. We evaluated MDCT‐related prognostic factors and non‐curative surgical factors and compared these factors with pathological results.Results: MDCT‐diagnosed category T (primary tumor invasion) included both prognostic factors and non‐curative surgical factors but not category N (lymph node metastasis). Multivariate analysis identified MDCT‐based suspected arterial invasion as an independent prognostic factor. In patients suspected of arterial invasion by MDCT, the 3‐year overall survival rate was only 39% and the curative resection ratio was only 33%, because of the high positive surgical dissected margin.Conclusion: MDCT‐based suspected arterial invasion is a predictor of poor prognosis after surgery for biliary cancer and represents a non‐curative surgical factor associated with positive dissected margin. J. Surg. Oncol. 2010; 101:376–383.

Background The aim of this retrospective study was to determine the effect of surgical margin on the outcome of postoperative radiotherapy (RT) in patients with resected hilar biliary cancer. Methods The study subjects were 87 patients with hilar biliary cancer resected surgically before 2008. Based on the Japanese Society of Biliary Surgery (JSBS) criteria for diagnosis of biliary cancer, the surgical margin status was categorized as margin 1 (histopathologically margin negative, but cancer cells identified within 5 mm from the margin), margin 2 (histopathologically margin positive), and margin 0 (other margin status). Results The surgical margin was 1 or 2 in 44 patients and 21 of these patients underwent RT. The 3‐year overall survival and progression‐free survival rates of the RT and non‐RT groups were 47% and 23% (P = 0.0392), and 49% and 19% (P = 0.0197), respectively. Univariate and multivariate analyses identified RT as the only factor that influenced survival. Subgroup analysis showed that the effect of RT was dependent on pathologically negative lymph node metastasis and positive margin (margin 2). Conclusion Postoperative RT is beneficial for patients with margins 1 and 2, especially those who are lymph node metastasis negative and have histopathologically positive margin. J. Surg. Oncol. 2009;100:657–662.