Abstract Purpose: Establishment of a reliable method of predicting the efficacy of chemotherapy and radiotherapy is necessary to provide the most suitable treatment for each cancer patient. We investigated whether proteomic profiles of serum samples obtained from untreated patients were capable of being used to predict the efficacy of combined preoperative chemoradiotherapy against esophageal cancer. Experimental Design: Proteomic spectra were obtained from a training set of 27 serum samples (15 pathologically diagnosed responders to preoperative chemoradiotherapy and 12 nonresponders) by surface-enhanced laser desorption and ionization coupled with hybrid quadrupole time-of-flight mass spectrometry. A proteomic pattern prediction model was constructed from the training set by machine learning algorithms, and it was then tested with an independent validation set consisting of serum samples from 15 esophageal cancer patients in a blinded manner. Results: We selected a set of four mass peaks, at 7,420, 9,112, 17,123, and 12,867 m/z, from a total of 859 protein peaks, as perfectly distinguishing responders from nonresponders in the training set with a support vector machine algorithm. This set of peaks (i.e., the classifier) correctly diagnosed chemoradiosensitivity in 93.3% (14 of 15) of the cases in the validation set. Conclusions: Recent mass spectrometric approaches have revealed that serum contains a large volume of information that reflects the microenvironment of diseased organs. Although a multi-institutional large-scale study will be necessary to confirm each component of the classifier, there is a subtle but definite difference in serum proteomic profile between responders and nonresponders to chemoradiotherapy.

Supplementary Data from Expression and Gene Amplification of Actinin-4 in Invasive Ductal Carcinoma of the Pancreas

The role of tumor–stroma interactions in tumor immune microenvironment (TME) is attracting attention. We have previously reported that cancer-associated fibroblasts (CAFs) contribute to the progression of peritoneal metastasis (PM) in gastric cancer (GC), and M2 macrophages and mast cells also contribute to TME of PM. To elucidate the role of CAFs in TME, we established an immunocompetent mouse PM model with fibrosis, which reflects clinical features of TME. However, the involvement of CAFs in the immunosuppressive microenvironment remains unclear. In this study, we investigated the efficacy of Tranilast at modifying this immune tolerance by suppressing CAFs. The interaction between mouse myofibroblast cell line LmcMF and mouse GC cell line YTN16 on M2 macrophage migration was investigated, and the inhibitory effect of Tranilast was examined in vitro. Using C57BL/6J mouse PM model established using YTN16 with co-inoculation of LmcMF, TME of resected PM treated with or without Tranilast was analyzed by immunohistochemistry. The addition of YTN16 cell-conditioned medium to LmcMF cells enhanced CXCL12 expression and stimulated M2 macrophage migration, whereas Tranilast inhibited the migration ability of M2 macrophages by suppressing CXCL12 secretion from LmcMF. In PM model, Tranilast inhibited tumor growth and fibrosis, M2 macrophage, and mast cell infiltration and significantly promoted CD8 + lymphocyte infiltration into the tumor, leading to apoptosis of cancer cells by an immune response. Tranilast improved the immunosuppressive microenvironment by inhibiting CAF function in a mouse PM model. Tranilast is thus a promising candidate for the treatment of PM.

BACKGROUND:The lipid scavenger receptor cluster of differentiation 36 (CD36) has been shown to have a pro-metastatic function in several cancers. Adipose tissue, a favorable site for peritoneal metastasis (PM) from gastric cancer (GC), promotes this process by providing free fatty acids (FFAs); however, the role of CD36 in PM progression from GC remains to be elucidated.MATERIALS AND METHODS:We evaluated CD36 expression in the GC cells under various conditions. CD36 overexpressing (CD36OE) MKN45 cells were prepared and their migration and invasive properties were assessed. A PM mouse model was used to investigate the biological effects of palmitic acid (PA) and CD36. Furthermore, we examined the clinical role of CD36 expression in 82 human PM samples by immunohistochemical staining.RESULTS:Hypoxia markedly increased CD36 expression in GC cells. In normoxia, only CD36OE MKN45 cells treated with PA showed an increase in migration and invasion abilities. An increased expression of active Rac1 and Cdc42 was observed, which decreased following etomoxir treatment. Conversely, hypoxia increased those capacities of both vector and CD36OE MKN45 cells. In a mouse model transplanted with CD36OE MKN45 cells, more peritoneal tumors were observed in the high-fat diet group than those in the normal diet group. In clinical samples, 80% of PM lesions expressed CD36, consistent with hypoxic regions, indicating a significant association with prognosis.CONCLUSION:Our findings indicate that a hypoxia in the peritoneal cavity induces CD36 expression in GC cells, which contributes to PM through the uptake of FFAs.

症例は神経線維腫症1型（NF1）の57歳，女性．55歳時に子宮筋腫・空腸gastrointestinal stromal tumor（GIST）に対し，腹式子宮全摘・両側付属器摘出および空腸楔状切除術が施行された．術後2年5カ月目に十二指腸下行脚にGISTを認めたため，切除する方針とした．十二指腸局所切除を行ったが，壁欠損部が大きく一次縫合閉鎖では変形・狭窄をきたす可能性が高いため，有茎空腸を作成し空腸粘膜パッチによる再建を行った．術後透視で再建部位に変形・狭窄は認めず，経過良好であった．NF1患者の7％にGISTが合併し，多発しやすく低悪性と報告されている．その多くは小腸に発生すると報告されているが，病変が十二指腸の場合はその術式や再建法が問題となる．今回われわれはNF1に合併した十二指腸GISTに対し，局所切除および有茎空腸粘膜パッチを用いた再建を行い，良好な結果が得られたので報告する．

ispresentwithinthemesentery,thepossibilityofpseudoaneurysmformationmustbeborneinminddur-ingtreatment.

A gastrointestinal–airway fistula (GAF) after esophagectomy is a very serious postoperative complication that can cause severe respiratory complications due to digestive juice inflow. Generally, GAF is managed by invasive surgical treatment; less-invasive treatment has yet to be established. We performed esophageal stent placement (ESP) in three cases of GAF after esophagectomy. We assessed the usefulness of ESP through our clinical experience. All GAFs were successfully managed by ESP procedures. After the procedure, the stent positioning and expansion were appropriately evaluated by radiological assessments over time. The stent was removed after endoscopic confirmation of fistula closure on days 8, 23, and 71. Only one patient with a long-term indwelling stent developed a manageable secondary gastrobronchial fistula as a procedure-related complication. In conclusion, ESP was shown to be a less-invasive and effective therapeutic modality for the treatment of GAF.

We present a case in which we used a thoracoscopic approach for resection of multiple esophageal carcinomas diagnosed 33 years after surgery for esophageal achalasia. A 68-year-old Japanese man had been diagnosed with esophageal achalasia and underwent surgical treatment 33 years earlier. He was examined at our hospital for annual routine checkup in which upper gastrointestinal endoscopy showed a "0-IIb+IIa" lesion in the middle esophagus. Iodine staining revealed multiple irregularly shaped iodine-unstained areas, the diagnosis of which was esophageal carcinoma. Thoracoscopic subtotal esophagectomy was performed. Esophageal carcinoma may occur many years after surgery for esophageal achalasia, even if the passage symptoms have improved. So, long-term periodic follow-up is necessary for detection of carcinoma at an earlier stage.

The case was a 47-year-old man. He was admitted for Mallory-Weiss syndrome. He was administered a total of 900 mg diclofenac sodium for fever and abdominal pain for 9 days. On day 10, colonoscopy was performed for colon obstruction diaphragm-like stenosis, and endoscopic expansion was performed for splenic flexure obstruction. Recurrence of ileus ap-peared and so colonoscopy was performed again. The splenic flex part was only slightly enlarged, but stenosis on the ileum end was detected. We tried to perform endoscopic expansion but it was difficult because the stenosis area was in the ileocecum region. Therefore, ileocecum resection was performed on day 32 after onset. Although dimple-shaped scarring was observed in the serosa of the area of stricture of the terminal ileum and pathological findings showed the formation of an ulcer in the muscle layer, there were only non-specific findings without vasculitis or the formation of granuloma was noted. Based on the clinical course and the non-specific pathological findings, NSAID enteropathy was diagnosed.

In addition to the use of chemotherapeutic agents for the prevention of multiple liver metastases from colorectal cancer, the anti-vascular endothelial growth factor (VEGF) antibody, bevacizumab, is often used, and its effectiveness has been established. By contrast, it has been reported that the use of bevacizumab prior to or following surgery delays wound healing or liver regeneration. In this study, we investigated whether the administration of bevacizumab following hepatectomy inhibits remnant liver regeneration or the growth of remnant metastases. Mice were partially hepatectomized (31% of the liver was removed), transplanted with the murine colorectal cancer cell line, CT26, in the remnant lobe, and intraperitoneally injected with bevacizumab (4 mg/kg) for a total of 6 times. Serum VEGF levels were measured on day 1 following surgery, and each lobe of the liver was weighed on day 14. Serum VEGF levels in non-hepatectomized, tumor-bearing mice exceeded those in their non-tumor-bearing counterparts; however, the administration of bevacizumab did not reduce the serum VEGF levels. The volume of the liver lobe of the hepatectomized, CT26-transplanted and non-CT26-transplanted mice was 1,349.6 and 735.5 mg, respectively, indicating rapid growth of the CT26 transplant (p=0.023). The volume of the CT26-transplanted lobe of the bevacizumab-administered mice was 1,379.0 mg, which was not significantly different from that (1,349.6 mg) of the non-bevacizumab-administered mice. The volume of the remnant lobe of the bevacizumab-administered mice was 1,051.0 mg, which did not significantly differ from that (957.3 mg) of the non-bevacizumab-administered mice. The administration of bevacizumab following hepatectomy did not delay remnant liver regeneration, and did not suppress the growth of metastases in the remnant lobes or remnant liver regeneration.

症例は35歳女性．主訴は発熱および腹痛．整形外科にて手術予定のため入院中，突然に38度以上の発熱認め徐々に下腹部痛と全身状態悪化を認めた．体温38.5℃，血圧82/44mmhg，下腹部に限局する反跳痛伴う強い圧痛を認めた．検査所見では血小板7.7万個/mm3，CRP25.8 mg/dlと著名な炎症反応を認め，骨盤腹膜炎によるDICショックの治療を先行した．治療開始48時間後，ショック状態から回復したが腹痛と発熱を認め，膣培養からS.pyogenesを検出された．また，腹部超音波およびMRIにて腹水の増大を認めたため腹腔ドレナージを施行した．その後，第98病日にて軽快退院となった．今回われわれは，急激に進行するA群溶連菌感染症に対しDICの治療を先行し，ショック状態からの離脱後，A群溶連菌による骨盤腹膜炎に対し腹腔穿刺によるドレナージを行い救命しえたため若干の文献的考察を加え報告する．

PURPOSE: Colorectal cancer operations are semi-pollution operation, have risk with which the synthetic graft are infected. Colorectal cancer operation case with the abdominal aortic aneurysm was examined. METHODS: Colorectal cancer operation cases in 15 years of 1996-2010 years, about 1800 cases, with abdominal aortic aneurysm was examined. RESULTS: Colorectal cancer operation cases with the abdominal aortic aneurysm were 13 cases. Ten men cases, three female cases, and the mean ages are 78.1 +- 7.7 years old. The colorectal cancer are one case in the appendix, one case in the cecum, three cases in the ascending colon, one case in the transverse colon, six cases in the sigmoid colon. and one case in the rectum. Seven cases previously operated on colorectal cancer from aorta. Five cases previously operated on abdominal aortic aneurysm from colorectal cancer. One case operated on the abdominal aortic aneurysm and the large intestine cancer at the same time. In five cases that previously operate on the abdominal aortic aneurysm, One case is arrhythmia. Two cases got pneumonia. One case became an ileus with an anastomotic stenosis. In seven samples that previously operate on colorectal cancer, Two cases became ileuse. (One case was operated eight years later.) Pneumonia and ileus were prolonged to the case that operated at the same time. CONCLUSIONS: Colorectal cancer operation with abdominal aortic Aneurysm becomes postoperative ileus easily from other colorectal cancer operations. The case not open the abdomen and follow-up, for the aneurysm of aorta becomes postoperative ileus easily. Because the case not open the abdomen become ileus, our think that the cause of the ileus is not adhesion but an ischemic.

BACKGROUND/AIMS Anticancer drugs are essential to pancreatic cancer therapy. The multidrug-resistance 1 (MDR1) gene codes for one of the ATP binding cassette (ABC) transporters. The neutralizing antibody of MDR1 reduces the activity of MDR1 and may add to the sensitivity of anti-cancer drugs. We investigated the relationship of the single nucleotide polymorphisms (SNPs), 2677G and 3435C, in the MDR1 gene and the effect of the anti-MDR1 single chain antibody (scAb) using pancreatic cancer cell lines. METHODOLOGY We exposed the pancreatic cancer cell lines, AsCP-1, Panc-1, BxPC-3, MIAPaCa-2 and QGP-1 to 0.1-1,000µ g/mL of 5-FU for 72h and calculated the cytotoxic reactions. Combined therapy with an established anti-MDR1 neutralizing scAb and 10µg/mL of 5-FU was also performed. RESULTS AsCP-1 contained wild types of MDR1 2677G and 3435C, and showed the most 5-FU resistance. The anticancer effect of AsPC-1 increased with anti-MDR1 scAb, but the effect was not significant compared with other cell lines. CONCLUSIONS The cells with the wild type SNPs of MDR1 showed drug resistance, but we were not able to confirm a remarkable effect of the anti-MDR1 antibody.

症例は57歳男性． 殿部の違和感および腫瘤触知にて外来受診された． 骨盤CTでは，内部均一な造影効果に乏しい腫瘤性病変として描出された． 骨盤MRIにおいて腫瘍内部はT1強調画像で低信号，T2強調画像では高信号に層構造状の低信号として描出された．また，腫瘤は前立腺，直腸右側壁に接するように存在し，肛門挙筋を圧排する長径10cm大の腫瘤を認めた．骨盤MRIで侵襲性血管粘液囊腫（aggressive angiomyxoma）（以下AAM）に特徴的な所見を認めたため超音波ガイド下にて経皮的組織診を行いAAMと診断した． 手術は経会陰的に施行し，経皮的組織診を行った皮下組織を含めまた肛門挙筋と尿管を温存し腫瘍切除術を行った．術後18カ月局所再発の所見なく経過観察中である． AAMは良性軟部腫瘍と位置づけられているものの局所浸潤性で再発をきたしやすいため術前診断の重要性が示唆された．

We previously reported that the administration of bevacizumab for pancreatic neuroendocrine tumors inhibited angiogenesis in the host, resulting in tumor growth inhibition. In light of these results, we compared the effect of bevacizumab/gemcitabine/S-1 combination therapy vs. bevacizumab monotherapy. The QGP-1 pancreatic neuroendocrine carcinoma cell line and the BxPC-3 ductal cell carcinoma cell line were transplanted into the subcutaneous tissue of mice, and the mice were treated for 3 weeks with bevacizumab [50 mg/kg intraperitoneally (i.p.) twice weekly], gemcitabine (240 mg/kg i.p. once weekly) and S-1 (10 mg/kg orally five times weekly). The antitumor effect and side effects were evaluated by measuring the tumor volume and weight and by changes in body weight, respectively. The tumor volume became smaller (from the maximum volume) in the group treated with bevacizumab, gemcitabine and S-1 (BGS) and the group treated with bevacizumab and gemcitabine (BG). A significant difference was noted in the tumor weight between the BG group and the group treated with bevacizumab alone. A relatively significant decrease in the body weight was observed in the BGS and BG groups. We conclude that gemcitabine is appropriate as a drug used in combination with bevacizumab for pancreatic neuroendocrine tumors.

33 Background: In this study, we measured the mRNA expression level of cancer-critical genes from the gastric/colorectal cancer tissues obtained through endoscopic biopsy before treatments and compared its consistency with the sample tissues surgically resected from identical cases. Methods: The study was made on 13 gastric and 19 colorectal cancer cases with patients’ consent. We picked identical cases and measured mRNA expression levels from the tissues endoscopically taken before treatment and the surgically resected ones. For the measurement, DNP (DanenbergTumorProfile) method was used. Examination items are as follows: TS, DPD, TP, FPGS, GGH, DHFR, ERCC1, Topo-I, EGFR, and VEGF. Results: Upon comparing the consistency between endoscopically sampled biopsy tissues and surgically taken tissues from identical cases, it was found that eight out of ten items showed strong correlations in colorectal cancer cases. The results are as follows: FPGS(r=0.91, p<0.001); GGH(r=0.87, p<0.001); EGFR(r=0.86, p<0.001); Topo I (r=0.81, p<0.001); TS(r=0.79, p<0.001); DHFR(r=0.70, p<0.01); VEGF(r=0.67, p<0.01); and TP(r=0.62, p<0.05). In case of gastric cancers, strong correlations were found in three out of ten items with the following results: EGFR (r=0.98, p<0.001); TS (r=0.91, p<0.001; and DPD (r=0.74, p<0.05). Conclusions: Today’s progresses of preoperative chemotherapy and radiotherapy and developments of endoscopic and surgical treatments allow diverse options for treatments. In such circumstances, the significance of knowing the expression of cancer-critical genes between individuals before treatment in conducting custom-made treatment is profound. There are two issues in applying the expression of cancer-critical genes found through endoscopic biopsy: one is whether enough cancer cells can be obtained through biopsy, and the other is whether the sampled cancer cells reflect the characteristics of primary focus. While there remain issues to be addressed, certain results were achieved in this study. Currently, we are working on accumulating cases to compare them and find out whether the results can be applied to custom-made treatments.

胃切除術後30年経過して発症した腸重積症を経験した.症例は70歳の男性.30年前に胃潰瘍により幽門側胃切除術を施行されている.上腹部痛,吐血を主訴に当院初診となった.入院時腹部単純X線検査などにて腸閉塞と診断された.保存的加療を行ったが改善しないため手術を施行した.手術所見はBillrothⅡ法再建後で,Braun吻合部の約20cm肛側の輸出脚に逆行性の小腸重積を認めた.用手的整復は困難であり,かつ循環障害を認めていた.小腸を約15cm切除し端々吻合した.術後経過は比較的良好であり,第18病日に退院となった.術後2年経過しているが再発はない.胃切除後腸重積は稀な疾患であるが,手術の既往のある腸閉塞の鑑別診断には,本疾患も念頭において精査加療することが重要であると考えられる.

Type IV-A choledochal cysts (CCs) are a congenital biliary anomaly which involve dilatation of the extrahepatic and intrahepatic bile ducts. We present the case of a 30-year-old woman with type IV-A CC, on whom three-dimensional computed tomography (3D CT) and virtual endoscopy were performed. 3D CT revealed partial dilatation in the posterior branch of the intrahepatic bile duct and a relative stricture between it and the extrahepatic bile duct. Virtual endoscopy showed that this stricture was membrane-like and separated from the surrounding blood vessels. Based on these image findings, complete cyst resection, bile duct plasty for the stricture, and hepaticojejunostomy were safely performed. To the best of our knowledge, there are no reports of imaging by virtual endoscopy of the biliary tract which show the surrounding blood vessels running along the bile duct.

A 49-year-old man was admitted to another hospital with the complaint of difficulty in defecating. He underwent laparotomy, and investigation of the biopsy revealed a huge intraperitoneal tumor. He began to take imatinib in April 2008 following a diagnosis of gastrointestinal stromal tumor (GIST), but the tumor increased in size. He was referred to our hospital for oral administration of sunitinib to reduce the tumor size. The tumor was 30 cm in diameter, and there were several peritoneal metastases around the liver. He began to take sunitinib in February 2009. The tumor increased in size from August 2010 but a partial remission was noted. We performed cytoreductive surgery in April 2011 as palliative care, but the tumor size increased again in October. We performed cytoreductive surgery again, but he died in December 2011. Although cytoreductive surgery for GIST is a potential treatment option, we suggest supportive care.

The patient was a 30-year-old primipara. She delivered her first child by normal delivery accompanied with episiotomy. At the time of delivery, it was confirmed that the upper limbs of the child were protruding from the mother's anus, therefore consultation with the concerned department was requested. A vaginal examination revealed a laceration of about 5 cm in the posterior wall of the vagina, and there was an episiotomy wound of about 2 cm on the right rear side from the vulva. Normal skin lay between the episiotomy wound and the anus, and no continuity was observed. Rectal examination showed a laceration in the rectal mucosa, and the anal side was immediately adjacent to the oral side of the dentate line. Suspecting a recto-vaginal perforation, an emergency operation was performed. Laceration of the anterior rectal wall extended to about 4 cm, and an invasive examination confirmed a passage of about 1.5 cm between the walls. After placing full-thickness sutures on the vaginal walls, vertical mattress sutures were placed on the rectal walls. Thereafter her clinical course was satisfactory. Recto-vaginal perforation not resulting in perineal laceration associated with childbirth is a rare condition; several bibliographic considerations are included in this report.