Renal cell carcinoma (RCC) is a common urological malignancy. Patients with low stage RCC have a good prognosis by radical operation. On the other hand, advanced RCC do not respond to most treatment and survival is poor in such patients. Some immuno-therapies were performed to patients with advanced RCC, but the patients who obtained clinically meaningful benefit were very limited. To identify promising targets for novel therapeutic agents, numerous investigations have been carried out regarding the molecular mechanisms of tumor growth and progression. Recently, some molecular-targeting therapies, including anti-vascular endothelial growth factor agent, have demonstrated to prolong survival in phase II and III trials. However, such treatments also showed limited anti-tumoral effects and various severe side effects beyond expectation. These results necessitate more extensive and profound knowledge of pathological features to discuss the treatment strategies for RCC. We have been investigating the molecular mechanism of cancer cell invasion and metastasis in patients with RCC for last few years, and we have obtained several new findings and information about them. In this article, we will describe clinical and pathological significance of several invasion-related and/or angiogenesis-related factors, such as matrix metalloproteinases, thrombospondin, and hepatocyte growth factor/c-Met. These factors are well known to regulate invasive function, angiogenesis, and cancer cell proliferation in various malignant tumors, and animal experiments demonstrated that some selective molecular inhibitors of them could inhibit tumorigenicity and tumor development. Our studies show that some molecular inhibitors may provide a novel therapeutic approach to RCC.

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Although volunteering has attracted attention in Japan as a useful measure for evaluating the level of senior citizens'self-rated health and satisfaction, no study has focused on the benefits of volunteering by Japanese senior citizens. To elucidate the effects of volunteering by Japanese women on their own well-being, we collected data from 106 volunteers and 60 non-volunteers aged 60 years or over using a self-administered questionnaire that included questions about sociodemographic characteristics, physical conditions, self-rated health, meaning and satisfaction in life, and emotional support network. Significant differences were observed between the volunteer group and the non-volunteer group in "self-rated health," "frequency of consulting doctors," and "frequency of communicating with friends." Also, total score of "source of meaning and satisfaction in life" and total score of "emotional support network" were significantly higher in the volunteer group than in the non-volunteer group. After adjusting for the effects of other factors, "frequency of consulting doctors" and "emotional support network" remained significantly associated with the frequency of being a voluntary worker. The present study suggests that volunteering might partially contribute to improving the well-being of senior citizens. Further studies are needed to clarify the effects of volunteering on the well-being of senior citizens in an aging society.

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Although the prognosis of differentiated thyroid cancer is generally favorable, some patients develop progressive disease resulting in a life-threatening condition and occasionally fatal outcome. CD44v6 is known to be a marker linked to distant metastasis in several types of human malignancy. In the present study, we analyzed the expression of CD44v6 in primary tumors and recurrent disease in the regional lymph node and evaluated its correlation with clinical variables and prognostic factors in patients with differentiated thyroid cancer. CD44v6 expression in the primary tumor was immunohistochemically detected in 58 of 79 patients (73%). Among parameters investigated, none except patient age showed a correlation with CD44v6 expression; the rate of positivity for CD44v6 was significantly higher (p=0.023) in patients aged 50 years or less than in those aged over 50 years. During the follow-up period, 14 patients were found to have recurrent cancer in regional lymph nodes, and among these, distant metastases were later detected in bones and/or lungs in 6 patients. Although an overall correlation between the expression of CD44v6 in the regional recurrent site and in distant metastasis was not statistically significant, there was a tendency that patients with positive CD44v6 in the regional lymph nodes subsequently developed distant matastases. CD44v6 appears to play an important role in tumor progression in patients with differentiated thyroid cancer, particularly in terms of recurrent disease in regional lymph nodes.

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We herein describe a 71-year-old female case of cholangiocarcinoma. Computed tomography of the abdomen showed an infiltrating lesion with low attenuation and a dilatation of the intrahepatic bile duct in the lateral segment of the liver. Positron emission tomography and computed tomography (PET/CT) revealed that the area of increased metabolic activity was detected in the lateral segment and regional lymph nodes. The tumor was diagnosed to be intrahepatic cholangiocarcinoma with lymph node metastasis. The patient underwent a left hepatectomy, and segment 1 and a lymph node dissection. A histopathological examination showed a well differentiated adenocarcinoma which had metastasized to the dissected lymph nodes. The histopathological findings of the involved lymph nodes were same as those of the hepatic tumor. PET/CT imaging study would be useful in preoperative staging of cholangiocarcinoma.

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Epidermoid cysts of the spleen are relatively rare. Usually occurring in children and young adults, they are most often asymptomatic, though large cysts can cause symptoms. A 9-year-old Japanese girl was found to have proteinuria and microscopic hematuria by routine school urine testing. She was incidentally found to have an abdominal mass. On abdominal magnetic resonance imaging, a cyst measuring 12.7 cm × 12.6 cm × 14.7 cm was found in her left upper abdomen. The cyst was too large for nonoperative treatment. Given the patient's age, concerns over the risk of septicemia after splenectomy led to laparoscopic marsupialization surgery. On pathology, the lumen of the cyst was found to be lined with stratified squamous epithelium. A small area of epithelium was positive for Alcian blue and HBME-1, indicating its mesothelial origin. Markers that were present in a high concentration, such as CA125 in the serum and cystic fluid, and CEA in the cystic fluid, stained positively in the epithelium. This supported the idea that these markers were produced by the lining epithelium. Six months since the operation, the cyst has gradually increased in size to 11.9 cm × 8 cm. However, since the cyst is asymptomatic, the patient is under outpatient-follow-up without further treatment.

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A 48-year-old woman was admitted to our hospital with abdominal fullness and pain. A barium enema and endoscopy revealed a Borrmann type II-like tumor of the sigmoid colon. Biopsy specimens showed poorly differentiated adenocarcinoma. Sigmoidectomy with lymph nodes dissection was performed. The tumor histologically consisted of proliferation of large and polygonal cells showing an organoid, trabecular or rosette-like pattern. Many mitotic figures were also observed. The tumor cells were immunohistochemically positive for chromogranin A. These findings led us to a diagnosis of large cell neuroendocrine carcinoma (LCNEC). Six months after surgery, liver metastases, para-aortic lymph node metastases and local recurrence were identified, and we commenced to administer FOLFOX, a combination of l-leucovorin and 5-fluorouracil with oxaliplatin. After six courses, a partial response was observed. This entity of the colon is not clearly recognized at present. The clinicopathological characteristics of LCNEC of the colon must be defined so that an appropriate treatment can be developed. Since LCNEC of the lung has been reported to be of high-grade malignancy, LCNEC of the colon must be treated as potentially highly malignant. In addition, the present case suggested that FOLFOX is a promising treatment for LCNEC of the colon.

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