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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.

One of the major factors for successful DCs immunotherapy is thought to be the maintenance of the migratory activity of matured DCs. We evaluated the effectiveness of PSK on OK432-activated DCs, in terms of maturation, migration and induction of CTLs. When DCs were treated with both OK432 and PSK, migration ability of the DCs were significantly high as compared to OK432 alone preserving the beneficial effect of OK432 treatment. BRM cocktail treatment with OK432 and PSK induced high level of migration activity in activated DCs, suggesting a potential protocol for more effective DCs immunotherapy for cancer.

SUMMARY. Immunosuppressive acidic protein (IAP) suppresses several immune responses in vivo and in vitro , and high preoperative IAP levels could predict the impairment of the host's immunity. In this study prognostic significance of preoperative IAP levels was investigated in 68 esophageal cancer patients with curative resection and eight with non-curative resection. The curative group had significantly lower levels than the non-curative group (432 ± 183 mg/mL vs. 739 ± 235 mg/mL, P < 0.0001). The IAP levels were associated with T-status (P < 0.0001), lymphatic invasion (P < 0.05), and p-stages (P < 0.0001). When 5-year survival rate of patients with curative resection was compared by setting various cutoff values of IAP between high and low IAP groups, several cutoff points (400-580 mg/mL) were revealed to be significantly associated with survival. Setting cutoff value of IAP to 560 mg/mL resulted in a most significant difference of 5-year survival rate of patients between the high and low IAP groups (13.9% and 61.5%, P < 0.0001). These data indicate that pre-operative IAP level is a useful parameter to predict the prognosis of esophageal cancer patients after curative resection.

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.

症例は59歳の女性で, 健康診断の上部消化管内視鏡検査にて胃体中部大彎に約10mmの隆起性病変を指摘され, 生検にて胃カルチノイドと診断された. 血液検査では血清ガストリン値が2,069pg/mlと高値であった. 超音波内視鏡検査では粘膜下層までの浸潤が認められた. 胃カルチノイドの診断で手術を施行. 術中色素法によるセンチネルリンパ節 (sentinel node; 以下, SNと略記) 生検にて, SNがNo4dに2個同定され, 1個に転移が認められた. 幽門側胃切除術およびD2リンパ節郭清を施行した. 病理組織検査にて腫瘍は長径9mmで深達度がSM2であり, SNとして同定されたリンパ節以外にリンパ節転移は認めなかった. 胃粘膜に慢性萎縮像は認めなかった. 術後血清ガストリン値は正常化した. sm胃カルチノイドではsm胃癌と同等のリンパ節転移が認められることから, SN生検は術中の正確なリンパ節転移診断法として有用であると思われる.

症例は49歳,女性.下腹部痛を主訴に来院.虫垂炎,胆石症にて2度の開腹歴を有した.入院の上鎮痛剤にて経過観察するも腹痛は次第に増強し, 6時間後には右側腹部の膨隆と右下腹部の筋性防御を認めた.腹部CT検査では右側の後腹膜腔に集積したイレウス腸管と腹水を認めた.絞扼性イレウスの診断にて緊急手術を施行した. Treitz靱帯をヘルニア門として小腸のほとんどが右側の後腹膜腔に嵌入し絞扼されていた.輸出脚の回腸には強い鬱血と色調変化を認めたが,還納後に温生食に浸すと色調が回復した.腸切除をせずにヘルニア門を縫合閉鎖し手術を終了した.術後経過は良好であった. 傍十二指腸ヘルニアは検索しえた範囲では自験例を含め87例と稀な疾患で術前の確定診断は困難と思われた.本症例では画像上特徴的な所見も呈していたと考えられたが,手術既往歴もあり癒着によるイレウスとの鑑別は困難であった.

症例は19歳の女性, 学校検診にて胸部X線写真上, 左中肺野の径約9mmの腫瘤影を指摘された.経過観察にて腫瘤影の増大を認めたため胸腔鏡にて肺部分切除施行.術後の組織診にて胞巣状軟部肉腫との診断を得た.転移と考え全身検索を行ったが, 明らかな原発巣を指摘できなかった.現時点では原発か転移かは明らかでないが, 再発, 転移の兆候なく外来経過観察中である.

Thoracoscopic microwave coagulonecrotic therapy (TMCT) has been reported to be one of the useful approaches in the management of hepatocellular carcinoma (HCC) that is located in the subphrenic area of the liver.In the present study, TMCT was performed on a 75-year-old woman with HCCs and liver cirrhosis. On admission, computed tomography revealed low density areas [exceeding 3 cm in Couinaud's segment 8 (S8) and 1 cm in segment 2 (S2)]. TMCT was selected for the HCC in S8 because percutaneous ethanol injection therapy (PEIT) and transcatheter arterial embolization (TAE) were not effective and surgical resection was not possible due to hepatic dysfunction and multicentric carcinogenesis. A thoracoscope was introduced into the thoracic cavity through the 5 th intercostal space on the midaxillary line, and two other trocars were placed in the appropriate intercostal spaces along the anterior and posterior axillary lines. We treated the HCC in S8 with TMCT across the diaphragma using laparoscopic ultrasonography and in S2 with intraoperative PEIT to avoid complications due to its location near Glisson's sheath. The efficiency of the coagulation and ethanol injection was proven by employing postoperative enhanced computed tomography.It was suggested that multimodal minimally invasive treatment such as TMCT is effective when combined with interstinal therapy for multiple HCCs with liver cirrhosis.

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.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).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.The density of CD83(+) DCs and Foxp3(+) Tregs was inversely correlated with tumor progression and reflected the prognosis of gastric cancer.

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. 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. 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. Tight-junction-associated proteins, particularly claudin-4, may play important roles in determining invasiveness, metastatic potential, and survival in gastric cancer.

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.

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.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.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.OK-432 has a more profound effect on human DCs than TNF-alpha and may act through multiple signaling pathways.

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.

15000 Background: A tight junction is one of components of intercellular junctional complexes and play an important role in maintaining barrier function and cellular porlarity. Claudin, occluding, and ZO-1 are known as trans-membrane proteins which compose tight junction. Roles of these tight junction-associated proteins of gastric cancer is not yet determined. In this study, we investigated expression levels of these proteins in gastric cancer immunohistochemically and compared the results with clinicopathological features of the tumors and patient prognosis. Methods: One hundred and twenty-four gastric cancer patients underwent gastrectomy between 2000 and 2004 were included in this study. Formalin fixed and parafine embedded tissues were sliced into 4-μm sections and immunohistchemistry was performed using anti-claudin-4, anti-occluding and anti-ZO-1 antibodies. Stained slides were investigated and the incidence of positive cells was graded as: 0, negative; 1, < 20 %; 2, 20–80 %; 3, >80 %. Results: The expression of claudin-4, occludin, and ZO-1 was observed at the membrane, and the positivity rates in cancer tissues were 87.1%, 95.2% and 100%, respectively. In concerning with correlation between protein expression and clinicopathologic features, claudin-4 expression was significantly decreased in tumors with undifferentiated type adenocarcinoma (p No significant financial relationships to disclose.

13034 Background: We have previously reported that tumors with high orotate phosphoribosil transferase (OPRT) and low dihydropyrimidine dehydrogenase (DPD) mRNA expression levels showed remarkable sensitivity to 5-fluorouracil (5-FU) by real-time RT-PCR using fresh frozen (FF) tumor samples. However, the use of fresh frozen samples has some limitations. The use of formalin fixed parafine embedded (FFPE) samples has great advantage to apply these technologies for clinical settings. In order to investigate the feasibility of real-time RT-PCR from FFPE samples to predict sensitivitiy to 5-fluorouracil (5-FU), we investigated the gene expression levels of 5-FU metabolism-relating enzymes by real-time RT-PCR from FFPE samples and compared the results from FF samples in gastric and colorectal cancer. Methods: FFPE samples and FF samples were obtained from 46 patients with gastric cancer and 29 patients with colorectal cancer. Gene expression levels of tymidylate synthase (TS), OPRT, thymidine phosphorylase (TP) and DPD were determined by quantitative real-time RT-PCR. In FFPE samples tumor tissue was obtained using laser captured microdissection (LCM). Tumor sensitivity to 5-FU was evaluated by in vitro ATP assay. Results: Gene expression levels of TS, TP, DPD determined from FFPE samples significantly correlated with those from FF samples. Although respective gene expression levels alone failed to show signifcianct correlation with the in vitro 5-FU sensitivity, statistically significant correlation was noted either from the samples of FF or FFPE in both gastric (FF: r = 0.660, FFPE: r = 0.780) and colorectal cancer (FF: r = 0.780, FFPE: r = 0.660), when OPRT/DPD mRNA ratio was applied for comparison with the results of 5-FU sensitivity. Thus, high OPRT/DPD ratio determined from FFPE samples resulted in high sensitivity to 5-FU. Conclusions: From these results, it is suggested that sensitivity to 5-FU is predictable by quantitative RT-PCR using FFPE samples. Measurement of 5-FU metabolism-relating enzyme gene expression level from FFPE samples appeared to be feasible for predicting 5-FU sensitivity and to have great advantage to apply the molecular predicting assay in clinical settings. [Table: see text]

4143 Background: Five-fluorouracil (5-FU) is still one of the key-drug for chemotherapy in gastric and colorectal cancer. Therefore, prediction of 5-FU sensitivity is of great importance for chemot...

4200 Background: We had previously reported that peritoneal micrometastasis determined by CEA mRNA level in peritoneal washings using real-time quantitative RT-PCR (RQ-PCR) is a good predictor for ...