[Retrospective analysis of Charlson comorbidity index (CCI)].

Owing to the advance of supportive care and the development of molecular targeted therapies, the elderlies or patients who have comorbidities have been treated more than before. The assessment of the comorbidity is indispensable to select the appropriate treatment or the control of following therapy. Some indices to determine them have been developed in western countries but not in Japan. The index which is used most is the Charlson comorbidity index (CCI). This index has never been evaluated in Japan. So we investigated the utility of the index for Japanese population. We surveyed retrospectively 498 patients aged 65 or more patients with colon cancer, breast cancer, lung cancer that have been treated in our hospital during 2002-2007. According to CCI, patients are classified into three groups and verified 1-year and 3-year survival rate. 1-year survival rate was 76.9% in groups of 0 points, 83.5% in groups of1 -5 points, 75.0% in the group of six or more points respectively (p=0.19). 3-year survival rate were 59.0%, 63.1%, 75.0%, respectively (p=0.46). Multivariate analysis identified age (≥ 50), Sex (man), stage (III and IV) as significant predictors for worse OS at 3-year. However, there was no significant difference in CCI. There are some items which frequency is zero, so the items of CCI may not match to Japanese population. Presence of existing disease is an important factor for the cancer therapy, and it should be evaluated accurately. It is urgently necessary to develop an evaluation method and establish the scale.

[Are the Japanese guidelines for the management of hepatitis B virus reactivation being properly implemented ?].

Hepatitis B virus(HBV)reactivation has been reported as a fatal complication following systemic chemotherapy or other immunosuppressive therapies. The Japanese Guidelines for HBV reactivation were published in 2009. Despite the publication of these guidelines, there have been some reports of fulminant hepatitis B. Therefore, it was suggested that the guidelines were not yet been widely implemented. We investigated whether the guidelines had been implemented in our hospital. After the evaluation, it was determined that 89%of HBV cases were screened for the HBV surface antigen(HBs-Ag). Additionally, the screening for HBV surface antibody(HBs-Ab)and HBV core antibody(HBc-Ab)should be performed in cases negative for HBs-Ag, which was performed in only 17% of HBs-Ag-negative cases. It was concluded that the guidelines had not been implemented in our hospital. Therefore, we conducted educational activities to promote the implementation of the guidelines. Screening tests were performed in all 270 HBV cases between January and June 2013. Two antigen-positive carriers were identified. The rate of HBs-Ag-negative and/or HBc antibody -positive cases was 20.3%. Of these, 76.4%were tested using a DNA quantitative test, but DNA quantification did not increase in any case. HBV reactivation is expected to increase due to the development of new drugs and the use of diverse regimens. All physicians who perform immunotherapy and chemotherapy should immediately participate in educational activities.

Clinicopathological analysis for recurrence of stage Ib gastric cancer (according to the second English edition of the Japanese classification of gastric carcinoma).

BACKGROUND: The prognosis for patients with stage Ib (second English edition of the Japanese classification of gastric carcinoma) gastric cancer is promising, with an expected 5-year survival of 90%. Despite this relatively high survival rate, the outcome for patients who experience recurrence is poor. To date, however, prognostic and recurrence factors for stage Ib gastric cancer are poorly understood, and appropriate adjuvant chemotherapy protocols have not been developed. METHODS: We retrospectively analyzed data from 86 stage Ib gastric cancer patients who underwent curative gastrectomy to determine the rates and predictive factors of recurrence. RESULTS: Eleven patients showed recurrence, with a 12.8% 5-year cumulative recurrence rate. Nearly all of these patients were initially histologically diagnosed with poorly differentiated adenocarcinoma. Based on univariate analyses, recurrence was associated with gender and histological type. Multivariate analyses revealed that the only independent risk factor for recurrence was histologically undifferentiated-type adenocarcinoma. The 5-year survival rate of patients with undifferentiated-type adenocarcinoma was 84%. The predominant recurrence pattern was peritoneal dissemination, and was typically observed 1-3 years post-resection. CONCLUSION: This retrospective study identified undifferentiated-type adenocarcinoma as the only risk factor for recurrence in stage Ib gastric cancer patients. Although randomized controlled studies are necessary, stage Ib gastric cancer patients with this identified recurrence risk factor would be candidates for adjuvant chemotherapy.

A clinical and immunohistochemical study on gastrointestinal mesenchymal tumor (GIMT): RCAS1 as a predictor for recurrence of GIMT.

Gastrointestinal mesenchymal tumors (GIMTs) are the most common mesenchymal tumors of the gastrointestinal tract. RCAS1 (receptor-binding cancer antigen expressed on SiSo cells) is a cancer cell-surface antigen and has been identified as a prognostic factor in several cancer types. It is thought that tumor cells escape immune attack by expressing RCAS1, which induces apoptosis in receptor-positive immune cells. The current study was designed to elucidate the histogenesis of these tumors by using various immunohistochemical markers, and identify parameters that will help to establish the criteria of malignancy in the GIMT. We also discuss the clinicopathological significance of RCAS1 expression in the diagnosis and prognosis of GIMTs. A total of 70 cases of GIMTs were reviewed. Immunohistochemistry was performed between 1990 and 2000, with the avidin-biotin-peroxidase complex method on 3 microm-thick sections of formalin-fixed paraffin-embedded specimens of GIMTs. Antibodies to the following antigens were used: KIT (CD117), CD34 alpha-SMA, Desmin, cytokeratin, S-100 protein, p53, and RCAS1. Recurrence-free survival analysis was done with Stat View-J 5.0 statistical packages. Univariate analysis for a recurrence-free prognosis demonstrated that antibody detection of p53 expression (p=0.0333) and expression of RCAS1 (p=0.0008) is correlated with a significantly higher potential of recurrence. On multivariate analysis, tumor size and RCAS1 expression were independently and inversely correlated with recurrence-free survival. The expression of RCAS1 has not previously been reported in GIMT; indeed, our study suggests that the expression of RCAS1 is correlated with recurrence not only in carcinomas, but also in mesenchymal tumors.

Amplification/overexpression of Aurora-A in human gastric carcinoma: potential role in differentiated type gastric carcinogenesis.

Aurora-A encodes a cell cycle regulated serine/threonine kinase that has essential functions for centrosome maturation and chromosome segregation. Aurora-A is amplified and overexpressed in various human carcinomas and is suggested to be a potential oncogene. To clarify the potential role of Aurora-A in human gastric carcinoma, we examined the amplification and expression in both tumor cell lines and primary carcinoma. We examined the amplification and overexpression of Aurora-A in 9 gastric carcinoma cell lines and 88 primary gastric carcinomas using Southern and Northern blot analysis, and confirmed a protein expression by immunohistochemical staining. We also investigated the relationship between Aurora-A overexpression and clinicopathological features of the tumors. Aurora-A amplification and overexpression was observed in 29% and 44.4% of cell lines and 12.5% and 41% of primary carcinomas, respectively. There was discordance between gene amplification and transcript expression, since in a previous study DNA amplification was the main mechanism for Aurora-A activation. Aurora-A overexpression exhibited significant association with increasing age and differentiated type gastric carcinoma. It was also detected in early stage gastric cancer as well as in gastric intestinal metaplasia, which is considered as a common precursor lesion for the differentiated type gastric carcinoma, and severe dysplastic cells showed stronger protein expression. We concluded that Aurora-A overexpression may well be involved in differentiated type gastric carcinogenesis. Further evaluation of the possible roles of Aurora-A and the regulation of Aurora-A expression in malignant cells will be critically important for the development of new strategies aimed at controlling the growth of malignant cells.

Tumor suppression effect using NK4, a molecule acting as an antagonist of HGF, on human gastric carcinomas.

Hepatocyte growth factor (HGF) is involved in malignant behavior of cancers as a mediator of tumor-stromal interactions, facilitating tumor invasion and metastasis. We have investigated whether a blockade of HGF using recombinant NK4, an HGF antagonist, would lead to growth inhibition of the human gastric carcinoma cell line, TMK1. To evaluate the function of endogenous NK4 and investigate its potential inhibitory effect, TMK1 cells were transfected with NK4 plasmid. After selection, NK4-expressing cells (T11) were obtained, and cell growth was evaluated. Significant growth inhibition was observed in the T11-group compared to the control both in vitro and in vivo. Moreover, we investigated the effect of exogenous NK4 transferred by an adenovirus vector (AdCMV.NK4). Cell proliferation of AdCMV.NK4 infected TMK1 cells was significantly inhibited compared with the control group. We also assessed the in vivo tumor suppression effect of AdCMV.NK4. The tumor volume following treatment with AdCMV.NK4 was significantly inhibited compared to that of the control group. These findings indicate that NK4 gene expression has a potential role in controlling proliferation of cancer cells. In conclusion, NK4 is a promising therapeutic agent and its gene delivery may be a new approach to treating patients with advanced gastric cancer.