症例は70歳，男性．腹痛，嘔吐を主訴に当院受診．腹部CT検査でS状結腸にhigh densityな残渣を認め，周囲にフリーエアーを認めた．食事内容と摂取状況より餅によるS状結腸穿孔と診断し，緊急開腹手術を施行した．手術所見ではS状結腸に穿孔を認め，穿孔部直下に硬い餅を触知した．全身状態が安定していたため，S状結腸を部分切除し，吻合術を行った．切除標本では硬化した餅が穿孔部には陥入し，餅の圧迫による潰瘍形成も認めた．餅によりS状結腸穿孔をきたした稀な症例を経験したので報告する．

The Hippo pathway significantly correlates with organ size control and tumorigenesis. The activity of YAP/TAZ, a transducer of the Hippo pathway, is required to sustain self-renewal and tumor-initiation capacities in cancer stem cells (CSCs). But, upstream signals that control the mammalian Hippo pathway have not been well understood. Here, we reveal a connection between the Protease-activated receptor 1 (PAR1) signaling pathway and the Hippo-YAP pathway in gastric cancer stem-like cells. The selective PAR1 agonist TFLLR-NH2 induces an increase in the fraction of side population cells which is enriched in CSCs, and promotes tumorigenesis, multi cancer drug resistance, cell morphological change, and cell invasion which are characteristics of CSCs. In addition, PAR1 activation inhibits the Hippo-YAP pathway kinase Lats via Rho GTPase. Lats kinase inhibition in turn results in increased nuclear localization of dephosphorylated YAP. Furthermore, PAR1 activation confers CSCs related traits via the Hippo-YAP pathway, and the Hippo-YAP pathway correlates with epithelial mesenchymal transition which is induced by PAR1 activation. Our research suggests that the PAR1 signaling deeply participates in the ability of multi drug resistance and tumorigenesis through interactions with the Hippo-YAP pathway signaling in gastric cancer stem-like cells. We presume that inhibited YAP is a new therapeutic target in the treatment human gastric cancer invasion and metastasis by dysregulated PAR1 or its agonists. The Hippo pathway significantly correlates with organ size control and tumorigenesis. The activity of YAP/TAZ, a transducer of the Hippo pathway, is required to sustain self-renewal and tumor-initiation capacities in cancer stem cells (CSCs). But, upstream signals that control the mammalian Hippo pathway have not been well understood. Here, we reveal a connection between the Protease-activated receptor 1 (PAR1) signaling pathway and the Hippo-YAP pathway in gastric cancer stem-like cells. The selective PAR1 agonist TFLLR-NH2 induces an increase in the fraction of side population cells which is enriched in CSCs, and promotes tumorigenesis, multi cancer drug resistance, cell morphological change, and cell invasion which are characteristics of CSCs. In addition, PAR1 activation inhibits the Hippo-YAP pathway kinase Lats via Rho GTPase. Lats kinase inhibition in turn results in increased nuclear localization of Dephosphorylated YAP. Furthermore, PAR1 activation confers CSCs related traits via the Hippo-YAP pathway, and the Hippo-YAP pathway correlates with epithelial mesenchymal transition which is induced by PAR1 activation. Our research suggests that the PAR1 signaling deeply participates in the ability of multi drug resistance and tumorigenesis through interactions with the Hippo-YAP pathway signaling in gastric cancer stem-like cells. We presume that inhibited YAP is a new therapeutic target in the treatment human gastric cancer invasion and metastasis by dysregulated PAR1 or its agonists.

症例は77歳の男性で，1990年に膀胱癌に対して膀胱全摘+Indiana pouch造設術を施行した．2012年7月に血尿を認め，CTでIndiana pouch内に隆起性病変，リンパ節転移，多発肝転移を認めた．Indiana pouch内の腫瘍からの生検で大腸高分化腺癌と診断された．遠隔転移を伴う大腸癌であり，まずmFOLFOX6+bevacizumab療法を6クール施行した．化学療法後に原発巣およびリンパ節転移，肝転移の縮小を認め，Indiana pouch摘出術+尿管皮膚瘻造設を施行した．以降，化学療法を継続中である．Indiana pouch内に発生した大腸癌の報告は現在までに自験例を含めて11例のみであり，非常にまれである．若干の文献的考察を含めて報告する．

205 Background: Intractable ascites associated with cancerous ascites causes severe abdominal distention, loss of appetite, poor nutritional condition and reduce the quality of life. We treat patients suffering from cancerous ascites by Cell-free and Concentrated Ascites Reinfusion Therapy (CART). But, cancerous ascites contains a lot of cellular components, and it easily cause filter obstruction. So we applied new method of CART: KM-CART in cancerous ascites patients. This CART system has a filter cleaning function, so the system has less incidence of filter obstruction. We report on our experience on CART for patients with cancerous ascites. Methods: Since November 2009 to August 2014, we applied CART in 31 cases of cancerous ascites (gastric cancer, 13; colorectal cancer, 6; pancreatic cancer, 10; others, 2). Results: On average, 3.8kg (range 1.2-7.5kg) of ascites were filtrated and concentrated to 440g (70-1110g). In all cases abdominal distention disappeared and abdominal girth decreased. Side effect was only mild fever on 11 cases. Conclusions: CART is safe and effective treatment for patients with cancerous ascites. This treatment may be able to improve quality of life with peritoneal dissemination.

BACKGROUND/AIM The expression of the CD44 variant exon 9 (CD44v9) was investigated in order to elucidate its significance for cancer stem cells in circulating human colorectal cancer cells (CTCs). MATERIALS AND METHODS After peripheral blood was drawn from patients with colorectal cancer, CTCs were collected. Using the reverse transcription-polymerase chain reaction method, we examined the relationship between expression of CD44v9 mRNA and prognosis. RESULTS In 60 out of 150 patients with colorectal cancer, expression of CD44v9 mRNA was positive in CTCs. In patients with stage III disease, the 5-year survival rate was 89% for patients with negative CD44v9 expression, whereas it was 52.4% in patients with positive expression (p<0.05). In patients with stage IV unresectable cancer, the 2-year survival rate was 70.1% in cases with CD44v9-negative expression and 33.3% in cases of positive expression (p<0.05). CONCLUSION CD44v9 mRNA in the CTCs of colorectal cancer is useful as a factor predicting recurrence, prognosis, and treatment efficacy.

The increased invasiveness of colorectal cancer cells is important for progression and metastasis to the surrounding organs. According to recent molecular biological studies, signaling through transmembrane Prokineticin-Receptor2(PK-R2) is likely involved in the ability of tumor cell to invade. However, no studies have evaluated the relationship between PK-R2 expression, ability of cancer to invade/metastasize, and patient prognosis in cases of resected colorectal cancer. Accordingly, we have examined these factors in the present study.Immunohistochemical staining was performed to detect PK-R2 in the primary lesion and adjacent normal large intestine mucosa of 324 colorectal cancer patients who underwent resection surgery at our department. Additionally, we conducted clinicopathologic examinations and analyzed patient prognoses with the Kaplan-Meier method. Further, multivariate analysis was conducted using a cox-proportional hazard model.PK-R2 expression was observed on the cellular membrane of the primary lesion in 147 of 324 cases (45.3%) of human colorectal cancer. PK-R2 expression was associated with a higher incidence of vascular invasion, lymph node metastasis, hepatic metastasis, and hematogenous metastasis. Further, prevalence of PK-R2 expression increased as tumor stage increased. In stage III curative resection cases, where recurrence is the most serious problem, cases that expressed PK-R2 had a significantly lower 5-year survival rate (82.1% versus 66.8%) and higher recurrence compared to those cases with no PK-R2 expression. In the multivariate analysis for prognosis, PK-R2 expression was found to be an independent factor(ratio2.621).PK-R2 expression could be one of the new prognostic factors in human colorectal cancer.

94 Background: Side Population (SP) is a FCM term to define cell clusters with strong ability to efflux DNA dye Hoechst 33342 by ABC transporters. In some cases, cancer stem-like cells (CSLCs) were identified using the FCM-based SP technique and SP cells had ability of drug resistance because SP cells were expressed ABC transporter. CSLCs may generate tumors through the stem cell processes of self-renewal and differentiation into multiple cell types. Such cells are proposed to persist in tumors as a distinct population and cause relapse and metastasis by giving rise to new tumors. We had showed PAR1 had an intimate involved in gastric cancer metastasis. And PAR1 contributed to leukemic stem cell maintenance. So we studied PAR1 induced SP cells acquired the ability of drug resistance in gastric cancer. Methods: MKN45 cells stably expressing PAR1 (45-PAR1) were generated in our laboratory. siRNA against PAR1 was synthesized. We studied the change in fraction of SP cell, when PAR1-expressing cell (45-PAR1 and MKN74), PAR1-null expressing cell MKN45 and inhibited PAR1-expressing MKN74 by PAR1 siRNA (74-PAR1siRNA) were treated with PAR1 agonist TFLLR-NH2 or TFLLR-NH2 plus PAR1 selective antagonist SCH79797. And, we compared the drug resistance using paclitaxel, cisplatin and 5-FU and researched ABC transporter expression in MKN45, 45-PAR1 and MKN74 with TFLLR-NH2 or SCH79797 or PAR1 siRNA. Results: We showed the fraction of SP cells in 45-PAR1 and MKN74 achieved dramatic increases by TFLLR-NH2. But, the fraction of SP cells in MKN45 and 74-PAR1siRNA remained about the same by TFLLR-NH2. When treated with SCH79797, the fraction of SP cells remained about the same, too. As for drug resistance assay, 45-PAR1 and MKN74 achieved the same strong resistance of the SP cells by TFLLR-NH2. But, MKN45 and 74-PAR1siRNA were not able to obtain the drug resistance. When treated with TFLLR-NH2, 45-PAR1 and MKN74 showed the high expression of ABCG1 and MRP1, that proteins are ABC transporters, compared to MKN45 and 74-PAR1siRNA. These expression levels in 45-PAR1 and MKN74 with TFLLR-NH2 were equal to the SP cells. Conclusions: PAR1 is closely-involved in that gastric cancer cells achieved the drug resistance and were led to SP enriched in CSLCs.

In addition to the general surgical-site infection prevention measures in colorectal cancer surgery, we performed a simple subcutaneous scrubbing procedure with gauze at the time of abdominal closure, which reduced the incidence of wound infections. There are 289 patients whose primary colon cancer lesions were removed by elective surgeries. They were divided into Group A (74 patients with no wound infection prevention measures who were treated from 2002 to 2003), Group B (76 patients with wound infection prevention measures who were treated from 2007 to 2008), and Group C (139 patients with subcutaneous scrubbing with gauze plus the measures in Group B who were treated from 2009 to 2012). The incidence in Group A was 23%, while the corresponding values in Group B and Group C were 14.5% and 2.9%, respectively. The incidence of wound infections was substantially reduced by additional subcutaneous scrubbing with a saline solution and gauze during closure of a surgical incision. This very simple procedure was considered useful for surgical site infection prevention.

We report a case of a splenic inflammatory myofibroblastic tumor (IMT). A 40-year-old man presented with left back pain and was found to have a 4 cm splenic mass by ultrasonography. Abdominal enhanced CT and MRI revealed no definitive diagnosis. Since fluorine-18-FDG-PET showed high FDG accumulation in the spleen, we performed laparoscopic splenectomy for suspected malignant tumor. It was histopathologically diagnosed as primary splenic IMT. The postoperative course was uneventful, without recurrence. We suggest that laparoscopic splenectomy is useful in treating splenic tumor, when determining a specific pathological diagnosis.