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Background: Bevacizumab (BEV) + Paclitaxel (PTX) and Eribulin represent the most frequently agents for the treatment of HER2-negative metastatic breast cancer (MBC). Eribulin has improved overall survival (OS) in EMBRACE trials. On the other hand, BEV has improved progression free survival (PFS) in several clinical studies, but not revealed prolongation of OS in them. There are difficult situations in making a clinical decision of when to choose which treatment option.Purpose: The purpose of this study is to compare two treatment strategies, Eribulin followed by BEV + PTX versus BEV + PTX followed by Eribulin. We evaluated whether sequential order of treatment affects survival benefit in patients who have been treated with both BEV + PTX and Eribulin in the real world. Methods: All patients who started BEV + PTX and Eribulin treatment for MBC from Aug-2011 to Jun-2018 were selected. Among 264 patients recorded in the TBCRG (14 institutions of Research Group) database, 180 patients had HER2-negative MBC. Of these, 84 patients were treated with both BEV + PTX and Eribulin sequentially regardless of treatment line. To evaluate the influence of sequential order, we compared the efficacy of Eribulin followed by BEV + PTX (arm E-B) to treatment with the reverse sequence (arm B-E). We used the two different analytical approaches to rubstify the findings from this study. Results: 38 patients were treated with E-B and 46 patients with the B-E sequence. We analyzed 60 cases within 3rd-line. In the entire cohort, the median time to failure of strategy (TFS) was 9.9 and 16.8 months in arm E-B and arm B-E, respectively (HR = 0.503, 95%CI 0.298-0.889, p=0.017). The respective median OS was 17.2 and 28.0 months (HR = 0.663, 95%CI 0.349-1.261. p=0.21). Similar HRs were derived from the PSMA and IPTWA cohort in TFS. Using PSMA, TFS was 9.0 and 14.1 months in arm E-B and arm B-E, respectively (HR = 0.406, 95%CI 0.172-0.955, p=0.039). The respective median OS was 12.8 and 24.0 months (HR = 0.61, 95%CI 0.232-1.6, p=0.315). Using IPTWA, TFS was 10.2 and 14.8 months in arm E-B and arm B-E, respectively (HR = 0.621, 95%CI 0.423-0.913, p=0.015). The respective median OS was 17.5 and 24.0 months (HR = 0.86, 95%CI 0.547-1.352, p=0.513).Conclusion: These results suggest that when patients with HER2-negative MBC are treated with both BEV + PTX and Eribulin, patients with prior BEV + PTX treatment is more likely to show more significant difference in results benefit than patients who are treated with prior Eribulin treatment. Citation Format: Koshi Matsui, Mitsuharu Earashi, Takuya Nagata, Akemi Yoshikawa, Wataru Fukushima, Zensei Nozaki, Yasuko Tanada, Kaeko Oyama, Katsuo Shimada, Kaoru Kiyohara, Tetsuro Shimizu, Keiko Iwata, Toru Yoshida, Kiichi Maeda, Akiyoshi Nakakura, Satoshi Morita, Tsutomu Fujii. Effect of Bevacizumab and Eribulin for metastatic breast cancer in the real world evaluated using the propensity score matching analysis (PSMA) and inverse probability of treatment weighting analysis (IPTWA) [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P2-15-12.

Background Median arcuate ligament syndrome (MALS), which results from compression of the median arcuate ligament (MAL), is a rare cause of abdominal pain and weight loss. Treatment is dissection of the MAL; however, the laparoscopic procedure is not yet established and it involves the risk of major vascular injury, especially in cases with an anomaly. Case presentation A 47-year-old man was evaluated at the hospital for epigastric pain. Contrast computed tomography scan revealed stenosis of the celiac artery origin due to the MAL. An Adachi V type vascular anomaly was also observed. Laparoscopic treatment was performed to release pressure on the celiac artery. Laparoscopic ultrasonography was used to less invasively confirm the release of the MAL. Despite a concomitant Adachi V type vascular anomaly, surgery was safely performed using the laparoscopic magnification view and intraoperative ultrasonography. Follow-up ultrasonography confirmed the celiac artery stenosis has not recurred. Conclusions A rare case of MALS with an Adachi V type vascular anomaly is presented and the laparoscopic treatment is detailed.

Objective The use of laparoscopic surgery for rectal disease is expected to provide good cosmetic benefits for patients postoperatively. However, this expectation is significantly reduced when a diverting ileostomy is created. We present a new technique that reduces the size of the skin wound by constructing a diverting ileostomy in the umbilicus. This procedure, diverting umbilical ileostomy (umbistoma) does not require special tools for its construction and closure. Methods Twenty-nine patients underwent treatment with umbilical diverting stoma, including five women and 24 men, with a mean age of 70 years (range: 40-88 years). At the time of ostomy closure, a new umbilicus was formed by subcutaneously suturing the wound to the fascia. In addition, we did not close the new umbilical upper and lower spaces, so as to allow open drainage of the healing wound. Results All procedures were completed successfully without any perioperative complications. Conclusions Our findings suggest that the umbilical diverting stoma could provide improved safety and cosmetic advantages in laparoscopic rectal resection.

Objectives This study aimed to compare open stoma (OS) creation with laparoscopic stoma (LS) creation considering the operation time, blood loss, time of oral intake, and complications. We also compared multiport LS and single-incision laparoscopic stoma (SILS) creation. Methods We reviewed the demographic data, diagnosis, indications, operation time, blood loss, time of oral intake, operative procedure, and complications of 50 patients who underwent stoma creation between April 2014 and April 2016. Results The mean blood loss was significantly lower in the LS group (7.85±18.4 ml) than in the OS group (38.1±73.2 ml; P=0.02). There were no statistical differences between the groups in terms of the operation time (LS, 72.1±32.7 min; OS, 61.2±31.2 min; P=0.23) or time of oral intake (LS, 1.0±0 days; OS, 1.91±2.71 days; P=0.17). Peristomal skin problems occurred in 11 patients (47.8%) in the OS group and 5 patients (18.5%) in the LS group. There were no statistically significant differences between the SILS and multiport LS groups, considering the operation time, amount of bleeding, and time of oral intake. Conclusions LS is comparable with OS in terms of operation time and time of oral intake and may cause lesser blood loss. Considering its advantages, LS is a useful approach for patients requiring biopsies or intra-abdominal inspection. SILS is a minimally invasive technique, suitable for patients in whom the stoma site is preoperatively decided.

We report a case of a mucin-producing intraductal papillary neoplasm of the intrahepatic bile duct (M-IPNB) diagnosed over a period of 6 years. A 64-year-old man underwent follow-up evaluations for an abdominal aortic aneurysm at our hospital. In 2009, a computed tomography (CT) scan revealed a simple hepatic cyst in segment 3 of the liver. Annual CT scans initially showed almost no change in the size or shape of the cyst. The cystic lesion, which measured 5 cm in 2014, had increased to 11 cm by 2015, and a solid component was detected within the cyst. A biliary cystic tumor was suspected and we performed a left lateral hepatectomy. Pathological examination showed that the papillary lesion in the cyst included adenocarcinoma and adenoma components. We diagnosed M-IPNB in 2015. Identification of the solid component of the cyst, as well as an increase in cyst diameter in the image analyses, was critical for diagnosis of M-IPNB.

A 39 year-old woman with malignant foot melanoma underwent wide excision of the primary tumor with a safety margin and sentinel lymph node biopsy (SLNB) for the right inguinal lymph node. SLNB was positive and a computed tomography (CT) scan revealed right iliac lymph node swelling. Positron emission tomography computed tomography (PET-CT) scan of the lymph nodes revealed abnormal uptake of fluorodeoxyglucose (FDG). We performed a laparoscopic pelvic lymph node obturator, iliac lymph node) dissection. During the operation, several black lymph nodes were observed in the iliac lymph node. Pathologically, the iliac lymph node consisted of metastasized atypical melanocytes. This surgical method for pelvic lymph node dissection is not a standard procedure among institutions. There have been no reported cases of malignant melanoma with pelvic lymph node metastasis treated by laparoscopic surgery. However, due to the minimally invasive technique, this method is worth considering to be used for pelvic lymph node dissection in malignant melanoma as well as other cancers in the field of urology or gynecology.

Background Thrombotic microangiopathy (TMA) pathogenesis after living donor liver transplantation (LDLT) is thought to be caused by release of unusually large von Willebrand factor multimers (UL-vWFMs) resulting from sinusoidal endothelial cell damage and induction of platelet adhesion and aggregation. A decrease in a disintegrin-like and metalloproteinase with thrombospondin type 1 motifs-13 (ADAMTS-13) that cleave UL-vWFMs might cause excessive UL-vWFMs activity and result in platelet thrombus formation. However, this phenomenon has not undergone a full pathologic assessment. Procedures A 60-year-old man was diagnosed with hepatitis C-related end-stage cirrhosis. His son was the donor, and he underwent LDLT. On postoperative day 44, his laboratory findings met most TMA diagnostic criteria, and he was diagnosed with TMA-like disorder (TMALD). Localization of CD42b as a platelet marker, vWF, and ADAMTS-13 in allograft tissue of this patient were evaluated using immunohistochemistry. Results CD42b expression was observed as platelet aggregates attached to hepatocytes or within the hepatocyte cytoplasm, a morphology called extravasated platelet aggregation (EPA). vWF expression was observed mainly as deposited compact clusters, and ADAMTS-13 expression resembled distinct dots throughout the liver tissue. Conclusion These findings suggest that EPA indicated sinusoidal endothelial cell damage followed by detachment, and vWF deposition resulted from UL-vWFM oversynthesis. ADAMTS-13 might be consumed in the allograft tissue to cleave UL-vWFMs, but ADAMTS-13 levels might be insufficient to cleave all the deposited UL-vWFMs. We present the case of an LDLT recipient diagnosed with TMALD using blood tests, which showed the presence of TMA pathogenesis in the allograft.

A 59-year-old man presenting with fecal occult blood visited our hospital. He was diagnosed with advanced lower rectal cancer, which was contiguous with the prostate and the left seminal vesicle. There were no metastatic lesions with lymph nodes or other organs. We performed laparoscopic total pelvic exenteration (LTPE) using transanal minimal invasive surgery technique with bilateral en bloc lateral lymph node dissection for advanced primary rectal cancer after neoadjuvant chemoradiotherapy. The total operative time was 760 min, and the estimated blood loss was 200 ml. LTPE is not well established technically, but it has many advantages including good visibility of the surgical field, less blood loss, and smaller wounds. A laparoscopic approach may be an appropriate choice for treating locally advanced lower rectal cancer, which requires TPE.

症例は61歳，女性．下腹部膨隆，下腿浮腫を自覚し，当院を受診した．血液検査で重度の鉄欠乏性貧血と低蛋白血症を認めた．上部消化管内視鏡検査では，胃全体に発赤を伴う大小多彩な浮腫状のポリープが多発しており，胃前庭部前壁ではポリープが密集して大きな集合体を形成していた．胃体下部小彎のポリープは生検でGroupIVと判定された．消化管シンチグラフィーでは，胃からの蛋白漏出を確認した．胃限局性のポリポーシスと，それに伴う鉄欠乏性貧血，蛋白漏出性胃腸症と診断した．また，一部のポリープは癌が強く疑われており，低蛋白血症や貧血は保存的治療に抵抗性であったため，胃全摘術の適応と判断した．術後の経過は良好で，貧血や低蛋白血症は速やかな改善を認めた．切除胃の病理組織学的診断で胃過形成性ポリポーシス，早期胃癌と診断した．

Sivelestat sodium hydrate (Ono Pharmaceutical Co., Osaka, Japan) is a selective inhibitor of neutrophil elastase (NE) and is effective in reducing acute lung injury associated with systemic inflammatory response syndrome (SIRS). We conducted a prospective randomized controlled study to investigate the efficacy of perioperative administration of sivelestat sodium hydrate to prevent postoperative acute lung injury in patients undergoing thoracoscopic esophagectomy and radical lymphadenectomy. Twenty-two patients with thoracic esophageal cancer underwent video-assisted thoracoscopic esophagectomy with extended lymph node dissection in our institution between April 2007 and November 2008. Using a double-blinded method, these patients were randomly assigned to one of two groups preoperatively. The active treatment group received sivelestat sodium hydrate intravenously for 72 hours starting at the beginning of surgery (sivelestat-treated group; n= 11), while the other group received saline (control group; n= 11). All patients were given methylprednisolone immediately before surgery. Postoperative clinical course was compared between the two groups. Two patients (one in each group) were discontinued from the study during the postoperative period because of surgery-related complications. Of the remaining 20 patients, 2 patients who developed pneumonia within a week after surgery were excluded from some laboratory analyses, so data from 18 patients (9 patients in each group) were analyzed based on the arterial oxygen pressure/fraction of inspired oxygen ratio, white blood cell count, serum C-reactive protein level, plasma cytokine levels, plasma NE level, and markers of alveolar type II epithelial cells. In the current study, the incidence of postoperative morbidity did not differ between the two groups. The median duration of SIRS in the sivelestat-treated group was significantly shorter than that in the control group: 17 (range 9-36) hours versus 49 (15-60) hours, respectively (P= 0.009). Concerning the parameters used for the diagnosis of SIRS, the median heart rates on postoperative day (POD) 2 were significantly lower in the sivelestat-treated group than in the control group (P= 0.007). The median arterial oxygen pressure/fraction of inspired oxygen ratio of the sivelestat-treated group were significantly higher than those of the control group on POD 1 and POD 7 (POD 1: 372.0 [range 284.0-475.0] vs 322.5 [243.5-380.0], respectively, P= 0.040; POD 7: 377.2 [339.5-430.0] vs 357.6 [240.0-392.8], P= 0.031). Postoperative white blood cell counts, serum C-reactive protein levels, plasma interleukin-1beta, tumor necrosis factor-alpha levels, and plasma NE levels did not differ significantly between the two groups at any point during the postoperative course, nor did serum Krebs von den Lungen 6, surfactant protein-A, or surfactant protein-D levels, which were used as markers of alveolar type II epithelial cells to evaluate the severity of lung injury. Plasma interleukin-8 levels were significantly lower in the sivelestat-treated group than in the control group on POD 3 (P= 0.040). In conclusion, perioperative administration of sivelestat sodium hydrate (starting at the beginning of surgery) mitigated postoperative hypoxia, partially suppressed postoperative hypercytokinemia, shortened the duration of SIRS, and stabilized postoperative circulatory status after thoracoscopic esophagectomy.

患者は70代後半の男性．飲酒中に酸性洗剤を誤飲した．10日後，心窩部痛および吐血にて救急外来を受診，上部消化管内視鏡検査で胃体上部後壁の潰瘍から出血を認め，止血処置を行い入院となった．翌日の内視鏡検査では，噴門直下から胃体下部にかけて全周性の糜爛を形成していた．しかし食道および幽門部には粘膜傷害を認めなかった．その後噴門部および胃体部で瘢痕性の狭窄を生じ，経口摂取不能となった．そのため，入院43日目に胃全摘術，R-Y再建術を施行した．病理組織診断は，粘膜下層に高度の線維化を伴う腐食性胃炎であった．腐食性胃炎は酸・アルカリ性薬剤など組織傷害性の強い薬物飲用により生じ，その程度はさまざまである．腐食性食道炎の併発が多く，また瘢痕性狭窄は幽門部に多い．本症例のように食道および幽門部に器質性変化を認めず，噴門部および胃体部で狭窄をきたした症例は稀である．

胃切除術後に発症した多発胃石による腸閉塞の1例を経験した.症例は82歳の女性. 58歳時に十二指腸潰瘍に対して広範囲胃切除術が施行されている.突然の腹痛と嘔吐が出現し,腸閉塞の診断で当科入院となった.胃内視鏡検査で,胃内に約4cm大の黒色楕円形異物を認め破砕除去を行った.症状が継続するため施行した腹部CT検査で,拡張腸管の末端部に内部不均一な腫瘤を認めたため,胃石の腸管移行による腸閉塞と診断し手術を施行した. Treitz靱帯より200cmの空腸に胃石を認めたため,腸壁を切開し胃石の摘出を行った.胃石は大きさ3.Ocm大で黒色楕円形を呈していた.成分は98%以上がタンニン酸で柿胃石と診断された. 胃石症は柿の過剰摂取や胃内容物排泄遅延が原因とされており,特に胃切除後症例などでは,食生活の指導や消化管運動調節剤の投与などを考慮すべきと思われる.診断は困難とされるが,食生活などの詳しい聴取が極めて重要である.

原発性虫垂癌症例に関して手術成績を検討した.対象は過去18年間に当科で手術施行した原発性虫垂癌症例の12例で,男女比3:9,平均年齢56.8歳(33～74歳),同期間の全大腸癌手術症例中0.69%の頻度であった.症状は右下腹部痛,右下腹部腫瘤,発熱などで,貧血にて精査後発見された無症状例は2例であった.術前に注腸造影検査,腹部CT,大腸内視鏡検査が施行され,虫垂癌の術前診断を得た症例は3例のみ,他は盲腸癌3例,癌性腹膜炎3例,回盲部膿瘍1例などであった.術式は結腸右半切除6例,回盲部切除4例,虫垂切除1例などであった.組織学的臨床病期はstage IIが3例,stage IIIaが1例,stage IVが8例で,stage IV症例では6例に腹膜播種を,3例に肝転移をともなっていた.術後遠隔成績は,4例が無再発生存中,8例は術後短期間に癌死,1生率66.7%,3生率,5生率ともに25%であった.特徴的な画像所見に乏しいため術前診断は困難で,手術時には進行した症例が多かったが,下腹部痛や腫瘤の鑑別診断のひとつとして念頭に置くべきと考えられた.

グリセリン浣腸によると考えられた直腸穿孔に起因する骨盤直腸窩膿瘍の1例を経験し,救命し得たので報告する.症例は90歳女性.平成11年3月13日より便秘,腹痛あり,近医からグリセリン浣腸を処方されていた.3月20日,腹痛,発熱を主訴に来院.ショック状態のため緊急入院となる.骨盤CT,下部消化管内視鏡検査より,グリセリン浣腸による外傷性直腸穿孔を疑い,便流遮断を目的に人工肛門造設術を施行した.3日後のCTで直腸周囲,骨盤直腸窩に多量の膿の貯留を認めた.坐骨直腸窩には膿瘍を認めなかったため,皮膚からの切開排膿は行わず,直腸潰瘍部からドレナージチューブを挿入し排膿した.約1カ月後にドレーン抜去し,その後の経過は良好であった,グリセリン浣腸は日常的に行われている治療であるが,穿孔等の危険があることに留意して,医療機関以外での使用には特に注意が必要と考えられた.

Veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) occurring after liver transplantation is a relatively rare complication but it often takes a life-threatening course. However, the detailed etiology and mechanism of VOD/SOS after liver transplantation (LT) remains unclear. We report two cases with rapidly progressive VOD/SOS after ABO-identical LT resistant to various therapies. In case 1, in which the patient underwent deceased-donor LT, the first episode of acute allograft rejection was triggered VOD/SOS, and the presence of donor non-specific anti-HLA antibodies was confirmed. The recipient died with graft failure on day 46 after transplantation. Case 2, in which the patient underwent living-donor LT from the mother, had neither rejection nor mechanical venous obstruction, but condition of the patient rapidly worsened and he died on day 13 after transplantation. This recipient's direct cross-match test for the donor's B lymphocyte was strongly positive, but that for T lymphocyte was negative. In both cases, neither stenosis of hepatic vein outflow tract nor C4d deposition in post-transplantation liver biopsy specimens and autopsy specimen was found. On the other hand, in both cases, the patient was transfusion unresponsive thrombocytopenia and hyperbilirubinemia persisted postoperatively, and glycoprotein Ⅰ bα was strongly stained in the neighboring centrilobular area (zone 3), especially in the space of Disse, and platelet phagocytosis was observed in Kupffer cells and hepatocytes around zone 3 such as clinical xenotransplantation of the liver in post-transplantation liver biopsy specimens. From the viewpoint of graft injury, VOD/SOS was considered that sustained sinusoidal endothelial cells injury resulted in bleeding in the space of Disse and led to around centrilobular hemorrhagic necrosis, and the fundamental cause was damage around centrilobular area including sinusoid by acute cellular rejection, antibody-mediated rejection or ischemic reperfusion injury. The extrasinusoidal platelet activation, aggregation, and phagocytosis of platelets were some of the main reasons for VOD/SOS and transfusion-resistant thrombocytopenia.

近年,固形癌細胞に発現しているFas-ligandの免疫回避能が注目されている.しかし,固形癌細胞におけるFas-ligand発現の臨床的意義に関する検討は少ない.そこで今回,大腸癌組織におけるFas-ligandの発現程度と臨床病理学的諸因子との関連について検討を行った.外科的治療の対象となった進行大腸癌77例を対象に抗ヒトFas-ligandウサギポリクローナル抗体を用い,免疫染色を行い評価した.Fas-ligandの発現は77例中33例(42.9%)に認められた.またFas-ligandの発現と肝転移(p

肺癌の小腸転移は稀である.小腸転移巣切除によりQOLの改善をみた2例を報告する 症例1は56歳,男性.脳転移を伴う右肺大細胞癌の診断で内科に入院した.持続する下血を認め,胃,大腸内視鏡検査を行ったが異常を認めず,小腸出血疑いにて手術を施行した.腫瘤は空腸壁と大網に散在し,腫瘤を含めた小腸部分切除,大網切除を施行した.肺大細胞癌の小腸転移であった.術後7カ月で死亡したが,その間経口摂取は良好であった.症例2は54歳,男性.脳転移を伴う左肺扁平上皮癌の診断で内科にて放射線・化学療法施行中に下血を認めた.胃,大腸内視鏡検査にて異常を認めず,小腸出血疑いにて手術を施行した.転移巣は回腸中ほどでS状結腸へ浸潤しており,ハルトマン手術,回腸部分切除を施行した.肺扁平上皮癌の小腸転移であった.術後6カ月で死亡したが,その間経口摂取は良好であった.肺癌の小腸転移巣の積極的な切除は患者のQOLの改善に有効である.

左腋窩副乳癌の1例を経験したので報告する.症例は65歳の女性. 10年前から自覚していた左腋窩の腫瘤が増大してきたため平成16年11月11日当科受診した.左腋窩に直径10mm大の皮下腫瘤を触れ,マンモグラフィーでは左腋窩にカテゴリー4の腫瘤影を認めた.吸引細胞診は陰性であったため局所麻酔下に切除生検を施行した.病理学的検索で副乳癌と診断し,全身麻酔下に局所の広範囲切除と腋窩リンパ節郭清 (level I) を施行した.切除標本に癌の遺残はなく,腋窩リンパ節転移も認めなかった.現在外来にてexemestane内服し経過観察中である.

p16(INK4a) is a tumor suppressor gene frequently inactivated by aberrant promoter hypermethylation. In the present study, p16(INK4a) methylation was evaluated in non-small cell lung cancer (NSCLC) using a quantitative assay and the clinical significance of the methylation was explored.A total of 244 tumor samples from formalin-fixed paraffin-embedded archives were examined in this study. p16(INK4a) methylation was analyzed by the fluorescence-based, real-time methylation-specific PCR assay, MethyLight. The quantitative methylation value was expressed as the percentage of methylated reference (PMR).The median level of p16(INK4) methylation was 0.55 PMR (range 0.00-503.4). The p16(INK4) methylation value was significantly higher in males (p = 0.005) and in squamous cell carcinoma (p = 0.018). Prognostic analysis using the Cox proportional hazard model showed that the p16(INK4a) methylation value was a significant prognostic factor (odds ratio, 1.005; 95% CI, 1.003 to 1.008; p0.0001). The p16(INK4a) methylation value remained a significant prognostic factor (p = 0.0004) in multivariate analysis including age, gender, histological type and clinical stage. Specimens were then classified into hypermethylated or non-hypermethylated groups based on the p16(INK4a) methylation value using various cut-offs from 1 to 100 PMR. There was no significant difference in prognosis between the two groups using a cut-off value of 1 PMR. On the other hand, there was a significant difference using 6 PMR or more as the cut-off value (p0.01).These results provide clear evidence for the prognostic significance of p16(INK4a) methylation in NSCLC using quantitative DNA methylation analysis. Careful assessment of DNA methylation is needed because qualitative methylation analysis may overestimate low levels of methylation, which have less clinical significance.

We report a case of surgically proved left-sided torsion of the greater omentum that caused secondary by untreated inguinal hernia. Case A 36-year-old man presented to our hospital with abdominal pain. He had been diagnosed with a left inguinal hernia, but he had not received any treatments. Contrast-enhanced computed tomography (CT) of the abdomen showed a large fat density mass below the Sigmoid colon and left inguinal hernia with incarcerated fat. Exploratory laparotomy revealed torsion of the greater omentum with small bloody ascites. The greater omentum was twisted into one and a half circles and entered into a left inguinal hernia. An omentectomy with a repair of left inguinal hernia was performed. A resected omentum was submitted for pathological examination, which showed hemorrhagic infarction. Omental torsion is a rare cause of acute abdominal pain but should be included in the differential diagnoses of acute abdomen, especially in patients with untreated inguinal hernia.

Thymidylate synthase (TS) and methylenetetrahydrofolate reductase (MTHFR) play important roles in folate metabolism. Previous studies have suggested that TS expression is a prognostic factor in non-small cell lung cancer (NSCLC). The TS gene has a variable number of tandem repeats (VNTR) and single nucleotide polymorphism (SNP) in the 5'-untranslated region, which are associated with TS expression. This association suggests that the TS polymorphism is a novel prognostic factor in NSCLC. In the present study, multiple genetic polymorphisms, TS VNTR, TS SNP and MTHFR C677T, were analyzed in NSCLC and compared with clinicopathological features and patients' prognoses.Genomic DNA was isolated from 294 surgically resected NSCLC tissues. The genotypes were determined by PCR and PCR-RFLP. The TS VNTR and SNP were combined, followed by functional stratification of H/H (3G/3G), H/L (2R/3G, 3G/3C) and L/L (2R/2R, 2R/3C, 3C/3C). Patients' prognoses were compared with TS and/or MTHFR genotype groups. TS was divided into the H- (H/H, H/L) and L-groups (L/L) according to functional stratification and MTHFR C677T was divided into C- (C/C) and T-groups (C/T, T/T).TS VNTR, the SNP and the TS functional type, along with MTHFR C677T, showed no significant association with clinicopathological factors. There were no differences in prognosis between each genotype or functional group when the TS and MTHFR groups were considered separately. However, we found a unique association between prognosis and the TS functional group in stage I NSCLC, taking both TS and MTHFR groups into consideration. The patients in the TS L-group survived longer than those in the H-group when limited to stage I and MTHFR C-group (p = 0.086). This relationship between the TS genotype group and prognosis was statistically significant in the subgroup of stage IB and MTHFR C-group (p = 0.030). In contrast, the patients in the TS H-group survived longer than those in the L-group when limited to stage I and MTHFR T-group (p = 0.052).The TS and MTHFR genotypes can be prognostic factors in NSCLC, where gene-gene interactions between the genotypes may occur. Further validation and investigation of the involvement of genotypes of folate metabolizing enzymes in the prognosis of NSCLC patients are required.

A 48-year-old man underwent subtotal esophagectomy for pStage III (pT 3 pN 3) thoracic esophageal carcinoma on June 20, 2002, in combination with chemotherapy (5-FU 500 mg/day day 1-14, CDDP 10 mg/day day 1-14, VDS 3 mg on days 1 and 8) before and after the operation. Recurrence was seen 7 months after the operation in right pleura and lower mediastinum. Chemo (same regimen)-radiotherapy (50 Gy) was then performed but without effect. Thereafter, lung and upper mediastinal metastases were found, and weekly administration of paclitaxel (70 mg/m2, day 1, 8, 15, q 4w) was initiated in combination with radiotherapy (40 Gy). Two cycles of treatment resulted in PR, and CR was achieved after the 8th cycle was completed. Although treatment was terminated after the 12 th cycle due to development of peripheral neuropathy (grade 2), CR was still maintained 8 months after the completion of treatment. These results suggested the effectiveness of the treatment in cases that show resistance to conventional 5-FU-based chemotherapy.

Methylenetetrahydrofolate reductase (MTHFR) plays a critical role in folate metabolism, which is an important pathway of the methyl donor for DNA methylation. The MTHFR gene has genetic variants (C667T and A1298C), which cause reduced enzyme activity. Impaired folate metabolism by these genetic variants of MTHFR could change the methylation pattern of DNA including promoter hypermethylation, which has been frequently observed in cancer. In this study, we compared the MTHFR genotypes and haplotype to the features of colorectal cancer focusing on the promoter methylation of tumor DNA.Genomic DNA was isolated from 194 colorectal cancer tissues and subjected to MTHFR genotyping by PCR-based restriction fragment length polymorphism analysis. The MTHFR haplotype was determined by combination of C667T and A1298C genotype and classified into 2 groups, high (H-haplotype) or low (L-haplotype) enzymatic activity of MTHFR. The methylation level of tumor suppressor genes (CDKN2A, hMLH1, ARF and TIMP3) was measured by a fluorescence-based, real-time methylation specific PCR method.There was no significant association of the clinicopathological features with either C667T genotype, A1298C genotype or haplotype of MTHFR. The methylation level of CDKN2A was higher in cancer with the L-haplotype of MTHFR than in that with the H-haplotype when cancers of proximal origin were considered (p=0.029). hMLH1 methylation also tended to be higher in proximal colon cancers of MTHFR L-haplotype (p=0.059). In addition, the proximal colon cancers showing CpG island methylator phenotype (CIMP) were significantly more frequent in L-haplotype than in H-haplotype.These results suggest that the haplotype with low enzymatic activity of MTHFR is linked with promoter hypermethylation and consequently modifies the risk of CIMP(+) proximal colon cancer development in the Japanese people. The relationship between MTHFR polymorphism and DNA methylation in the Japanese is contrary to the previous results in Caucasians. Further study is needed focusing on ethnic variations in the relationships among MTHFR polymorphism, DNA methylation and the development of CIMP(+) colorectal cancer.

MYOD1 promoter methylation occurs in various malignancies including colorectal cancer. We analyzed MYOD1 methylation in 80 colorectal cancer and 74 adjacent normal tissues using MethyLight, which enabled quantitative DNA methylation analysis. The measured methylation value was expressed as a percentage of methylated reference (PMR). The results were compared with clinicopathological features and patient prognosis in order to investigate whether MYOD1 methylation may serve as an independent prognostic factor of colorectal cancer. MYOD1 promoter methylation was detectable in all samples and was significantly higher in tumor compared to normal mucosa, where the median level of methylation was 5.3 PMR (range 0.03-133.4) in normal mucosa and 42.3 PMR (range 0.44-742.9) in tumor. The methylation value of MYOD1 was higher with elder patients both in normal colonic mucosa (p=0.034) and in cancer tissues (p=0.0012). Patients without MYOD1 hypermethylation showed significantly longer survival than those with hypermethylation (p=0.0077). In multivariate analysis of prognostic factors, MYOD1 hypermethylation was a significant prognostic factor (p=0.015) independent to patients' age. These results suggest that MYOD1 hypermethylation plays an important role in colorectal cancer and may be a novel prognostic factor. In addition, quantitative methylation analysis by MethyLight is encouraged for other genes showing age-related and non-cancer-specific methylation.

The purpose of this study was to evaluate the trypsinogen expression in human colorectal cancers. We observed the trypsinogen-1 mRNA expression in five of ten human colorectal cancer cell lines by reverse transcriptase-polymerase chain reaction (RT-PCR), and gelatinolytic activity in conditioned medium of cancer cells at acidic pH by gelatin zymography. Furthermore, trypsinogen protein expression was observed in 68 out of 154 (44.2%) surgical specimens of colorectal cancer immunohistochemically. However, there was no statistically significant relationship between the trypsinogen expression and the clinicopathological findings. These findings suggest that trypsinogen might be involved in cancer invasion and metastasis throughout the cancer progression.