[Outcomes of Bridge to Surgery for Obstructive Colorectal Cancer after Metallic Stent Placement in Our Hospital].

Recently, the endoscopic placement of self-expanding metallicstents (SEMSs)has become widespread for the treatment of acute malignant colorectal obstruction. This study was designed to evaluate the clinical outcomes of 22 patients with obstructive colorectal cancer who underwent SEMS placement as a bridge to surgery(BTS)from January 2012 to December 2015. The subjects comprised 15 men and 7 women with a mean age of 68.1 years. Placement and decompression were successfully achieved in all cases. No serious complications arose from the placement. After excluding 3 patients for whom preoperative chemotherapy or treatment for another disease was prioritized, the mean interval to surgery for the remaining 19 patients was 18.2 days. Operative anastomosis was performed in all patients except those who had tandem lesions. Although postoperative complications including minor leakage(n=1), surgical site infection(n=1), and ileus(n=1)were observed, the course was effective in most patients. Bridge to surgery is a relatively easy, safe, and effective method for the treatment of obstructive colorectal cancer that enables preoperative intestinal decompression and one-stage resection, preventing stoma creation.

CD83(+) dendritic cells and Foxp3(+) regulatory T cells in primary lesions and regional lymph nodes are inversely correlated with prognosis of gastric cancer.

BACKGROUND: Dendritic cells (DCs) are potent antigen-presenting cells that are central to the regulation, maturation, and maintenance of the cellular immune response against cancer. In contrast, CD4(+)CD25(+) regulatory T cells (Tregs) play a central role in self-tolerance and suppress antitumor immunity. In this study, we investigated the clinical significance of mature CD83(+) DCs and Foxp3(+) Tregs in the primary tumor and regional lymph nodes from the viewpoint of the two opposing players in the immune responses. METHODS: We investigated, immunohistochemically, the density of CD83(+) DCs and Foxp3(+) Tregs in primary lesions of gastric cancer (n = 123), as well as in regional lymph nodes with (n = 40) or without metastasis (n = 40). RESULTS: Decreased density of CD83(+) DCs and increased density of Foxp3(+) Tregs were observed in the primary tumor and metastatic lymph nodes. Density was significantly correlated with certain clinicopathological features. Poor prognosis was observed in patients with a low density of CD83(+) DCs and a high density of Foxp3(+) Tregs in primary lesions. For patients with metastatic lymph nodes, the density of CD83(+) DCs in negative lymph nodes was found to be an independent prognostic factor by multivariate analysis. CONCLUSION: The density of CD83(+) DCs and Foxp3(+) Tregs was inversely correlated with tumor progression and reflected the prognosis of gastric cancer.

Ornithine decarboxylase activity as a prognostic marker for colorectal cancer.

Ornithine decarboxylase (ODC) is a key enzyme in the biosynthesis of polyamines, which are essential for cell proliferation. ODC activity was measured in 47 colorectal cancer patients, 5 patients with adenoma of colorectum and 4 healthy volunteers. Mean ODC activities of cancer tissue, non-cancerous mucosa from cancer-bearing colorectum, adenoma tissue, and normal mucosa from healthy volunteers were 435+/-392, 154+/-173, 295+/-202, 103+/-60 pmol CO2/h/mg protein, respectively. ODC activity of cancer tissue or adenoma tissue was significantly higher than that of the others. Among colorectal cancer patients, ODC activity in cancer tissue was correlated with T factors, lymph node metastasis and stages. Patients with tumors that had high ODC activity (> or =350 pmol CO2/h/mg protein) showed a poor 10-year survival rate. These results suggest that ODC activity may be a useful marker for patients' prognosis after surgery.

[A case of advanced gastric cancer responding remarkably to neo-adjuvant combination chemotherapy using CPT-11 plus S-1].

Adjuvant chemotherapy for advanced gastric cancer has not yet been established. We report a patient with advanced gastric cancer responding remarkably to neo-adjuvant combination chemotherapy consisting of CPT-11 and S-1. The patient was a 69-year-old woman diagnosed with large type 3 advanced gastric cancer with esophageal invasion and having No.3 lymph node metastasis (cT3, cN1, cM0, cStage IIIA), treated with 2 courses of CPT-11 plus S-1 as neo-adjuvant chemotherapy. Computed tomography after neo-adjuvant chemotherapy showed improvement of gastric wall thickness and reduction of lymph node metastasis. Subsequently, she underwent an operation. There was no lymph node swelling,so we performed curative surgery consisting of total gastrectomy, splenectomy, cholecystectomy, and D 2 lymph node dissection. Histological diagnosis was pT2 (MP), pN1, pStage II, and estimation of the histological change by chemotherapy was Grade 2. The course after surgery was good, and she was treated by S-1 after discharge. To date, 8 months after surgery, there is no evidence of recurrence. Combination chemotherapy consisting of CPT-11 plus S-1 can be performed safely as a neo-adjuvant treatment, and may be an effective treatment modality for advanced gastric cancer.

Understanding the response of dendritic cells to activation by streptococcal preparation OK-432.

BACKGROUND: The streptococcal preparation OK-432 induces maturation of T cells and dendritic cells (DCs). However, the mechanisms by which OK-432 induces DC maturation are not well understood. MATERIALS AND METHODS: The effects of OK-432 and TNF-alpha on peripheral blood mononuclear cells (PBMCs) were compared. Antibody-based approaches were used to detect proteins characteristic of antigen-presenting cells and cytokines. Cytotoxicity was evaluated by measuring the release of LDH after incubation of effector and target cells. The TLR-4 levels were measured by real-time quantitative PCR. RESULTS: Changes in cell surface marker levels were detected in both treatment groups but OK-432 had a greater effect on induction of Th-1-type cytokines. Furthermore, TLR-4 mRNA was up-regulated in cells from two out of five patients in response to OK-432, but not in response to TNF-alpha. CONCLUSION: OK-432 has a more profound effect on human DCs than TNF-alpha and may act through multiple signaling pathways.

[Experimental study for a combination chemo-immunotherapy using dendritic cells].

This study was designed to seek for the optimal anticancer agents for a combination of chemotherapy and specific immunotherapy using dendritic cells (DC) in gastric cancer. We investigated the immuno-suppressive activity of anticancer agents on human peripheral blood mononuclear cells (PBMC), apoptosis inducing activity on gastric cancer cells and expression of Toll-like receptor (TLR)-4 mRNA on immatureDCs (iDCs) by paclitaxel (TXL) and docetaxel (TXT). We further compared the cytotoxicity of cytotixic T lymphocytes (CTLs) induced by DCs pulsed with tumor cell lysate and apoptotic cells induced by TXT. Although most of the anticancer agents demonstrated the suppression activity on proliferation of PBMC in a dose dependent manner, TXT, doxifluridine and irinotecan did not show the suppressive activity on PBMC even in the highest drug concentration. About 60% of gastric cancer cells demonstrated apoptosis after a 24-48 hour treatment with both TXL and TXT. Expression of TLR-4 mRNA in iDCs was up-regulated by TXT, not by TXL, and peaked at 2 hours after the treatment. CTLs induced by DCs pulsed with tumor cell lysate and apoptotic cells showed a similar killing activity to target cells. These results suggest that TXT appears to be an optimal anticancer agent for a combination therapy with chemotherapy and tumor specific immunotherapy using dendritic cells in gastric cancer.

Expression of tight-junction-associated proteins in human gastric cancer: downregulation of claudin-4 correlates with tumor aggressiveness and survival.

BACKGROUND: Claudin, occludin, and zonula occludens (ZO)-1 are known as tight-junction-associated proteins. The aim of this study was to examine the expression of these proteins in gastric carcinoma. METHODS: Gastric cancer tissues (n = 124) were obtained from 124 patients who underwent gastrectomy at our hospital between January 2000 and December 2004. The expression of the above tight-junction-associated proteins in carcinoma, normal mucosa, and metaplastic epithelium was examined using immunohistochemistry. In addition, the expression of claudin-4 mRNA was examined in fresh frozen tissue obtained from 34 patients. RESULTS: Significant correlations were seen between the expression of claudin-4, occludin, and ZO-1. In regard to claudin-4, significant correlations were seen between the expression of claudin-4 evaluated by immunohistochemistry and the expression of claudin-4 mRNA. Claudin-4 expression was significantly decreased in tumors with undifferentiated-type adenocarcinoma, advanced T stage, lymph node metastasis, and peritoneal metastasis. Occludin and ZO-1 expression was significantly decreased in tumors with undifferentiated-type adenocarcinoma. Overall survival was significantly shorter in patients with low claudin-4 expression. Cox multivariate analysis revealed that low claudin-4 expression was independently associated with significantly decreased overall survival. CONCLUSION: Tight-junction-associated proteins, particularly claudin-4, may play important roles in determining invasiveness, metastatic potential, and survival in gastric cancer.

Detection of cancer cells disseminated in bone marrow using real-time quantitative RT-PCR of CEA, CK19, and CK20 mRNA in patients with gastric cancer.

BACKGROUND: To determine the significance of bone marrow disseminated tumor cells in gastric cancer, we investigated the mRNA expression levels of carcinoembryonic antigen (CEA), cytokeratin 19 (CK19), and cytokeratin 20 (CK20) using the real-time quantitative reverse-transcription polymerase chain reaction (RQ-PCR). METHODS: Bone marrow samples were aspirated from the sternum at the time of surgery in 65 patients with resectable gastric cancer. Total RNA was extracted from bone marrow; and the expression levels of CEA, CK19, and CK20 mRNA were determined by RQ-PCR using an ABI PRISM 7000 and quantified against the GAPDH mRNA level. RESULTS: The detection limits of these genes were determined in the gastric cancer cell line MKN-45 and the colon cancer cell line C-1, which had been serially diluted in peripheral blood mononuclear cells (PBMCs). A rate of 1 cancer cell/million PBMCs was obtained by detecting CEA and CK19 mRNA in MKN-45 and by detecting CK20 mRNA in C-1. In the clinical samples, only 1 of the 65 gastric cancer patients (1.5%) who had stage IV disease was positive for CEA, CK19, and CK20 mRNA; none of CEA, CK19, or CK20 mRNA was positive in the remaining 64 patients. No significant correlation was observed between disseminated cancer cells in bone marrow and clinicopathological features, including simultaneous or metachronous hepatic metastasis and patient survival. CONCLUSION: The incidence of disseminated cancer cells in bone marrow in our study appears low, unlike that in previous reports. The significance of disseminated cancer cells in bone marrow may also be quite low in gastric cancer.