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Background: Overexpression of Galectin-3 (Gal-3), a β-galactoside binding protein, has been noted in many tumour types but its functional significance and clinical utility in gastric adenocarcinoma (GAC) are not well known. Methods: We studied 184 GAC patients characterised by histologic grade, sub-phenotypes (diffuse vs intestinal), and ethnicity (Asians vs North Americans). Immunohistochemistry was performed to assess the expression of Gal-3 in human GACs and we correlated it to the clinical outcomes. Cell proliferation, invasion, co-immunoprecipitation and kinase activity assays were done in genetically stable Gal-3 overexpressing GC cell lines and the parental counterparts to delineate the mechanisms of action and activity of inhibitors. Results: Most patients were men, Asian, and had a poorly differentiated GAC. Gal-3 was over-expressed in poorly differentiated (P=0.002) tumours and also in diffuse sub-phenotype (P=0.02). Gal-3 overexpression was associated with shorter overall survival (OS; P=0.026) in all patients. Although, Gal-3 over-expression was not prognostic in the Asian cohort (P=0.337), it was highly prognostic in the North American cohort (P=0.001). In a multivariate analysis, Gal-3 (P=0.001) and N-stage (P=

Programmed death ligand 1 (PD-L1) is a key protein upregulated by tumor cells to suppress immune responses. Tumor-associated macrophages (TAMs) play a major role in this immunosuppression, but the relationship between PD-L1 expression and TAMs remains unclear in gastric adenocarcinoma (GAC). We simultaneously examined expression of PD-L1 and TAMs in GAC. We performed immunohistochemical staining for PD-L1, CD68 (pan-macrophage), and CD163 (M2-like macrophage) in 217 GAC samples using a tissue microarray. Expression of PD-L1 and CD68- and CD163-positive cells was evaluated using the Cytoplasmic V2.0 algorithm in Aperio ImageScope software, and logistic regression analysis was used to compare expression patterns between groups. Thirty-one samples (14%) were positive for PD-L1 expression. The mean (± standard error) rates of infiltration were 6.83 ± 0.38% for CD68-positive cells and 6.16 ± 0.29% for CD163-positive cells. The mean rate of CD163-positive cell infiltration was significantly higher in diffuse GAC than in intestinal GAC (diffuse n = 111, 6.91%; intestinal n = 91, 5.26%; p = 0.006), but the mean rate of CD68-positive cell infiltration was similar between these types (p = 0.38). The mean infiltration rates of CD68- and CD163-positive cells in PD-L1-positive GAC were significantly higher than in PD-L1-negative GAC (CD68 p = 0.0002; CD163 p

New molecular biology-based methods of bacterial identification are expected to help elucidate the relationship between colorectal cancer (CRC) and intestinal microbiota. Although there is increasing evidence revealing the potential role of microbiota in CRC, it remains unclear whether microbial dysbiosis is the cause or the result of CRC onset. We investigated the changes of intestinal environments in CRC or adenoma. We analyzed 13 groups of microbiota, 8 types of organic acids, and pH in feces obtained from the following 3 groups: individuals with CRC, adenoma, and non-adenoma. Ninety-three patients with CRC and 49 healthy individuals (22 with adenoma and 27 without adenoma) were enrolled. The counts of total bacteria (10.3 ± 0.7 vs. 10.8 ± 0.3 log10 cells/g of feces; p

Background In some recently updated clinical guidelines, the fully humanized monoclonal antibody panitumumab, combined with irinotecan, has been recommended as an optional third-line chemotherapy for KRAS wild-type metastatic colorectal cancer (mCRC). The present prospective, multicenter phase II study evaluated the effectiveness and safety of short 15-minute panitumumab infusions. Patients and Methods From January 2011 to December 2011, patients with KRAS wild-type mCRC were enrolled at 8 centers. The key eligibility criteria were age ≥ 20 years and resistance or intolerance to irinotecan, fluoropyrimidine, and oxaliplatin. All patients received 6 mg/kg of panitumumab and 150 mg/m 2 or the previous tolerated dose of irinotecan, biweekly, until disease progression or unacceptable toxicity. The initial panitumumab infusion was 60 minutes, followed by a 30-minute infusion and then 15-minute infusions. The primary endpoint was the confirmed response rate using Response Evaluation Criteria In Solid Tumors, version 1.0. The secondary endpoints were progression-free survival, overall survival, and toxicity. The trial is registered in the University Hospital Medical Information Network Clinical Trials Registry (UMIN no. 000004647). Results Of the 43 patients, the median age was 62 years (range, 32-75 years), 58% were male, and the Eastern Cooperative Oncology Group performance status was 0 to 1. The total response rate was 37.2% (95% confidence interval [CI], 23.0-53.3), and the confirmed response rate was 18.6% (95% CI, 8.4-33.4). The median progression-free and overall survival were 5.8 months (95% CI, 3.3-8.4 months) and 13.6 months (95% CI, 10.8-16.5 months), respectively. The most frequent grade 3/4 toxicities were anorexia (12%), leukopenia (9%), and neutropenia (9%). Nine patients did not reach the 15-minute infusion, primarily because of disease progression. No infusion-related reactions were observed. Conclusion The short 15-minute panitumumab infusion regimen was well tolerated, without compromising safety or efficacy in patients with KRAS wild-type, oxaliplatin- and irinotecan-refractory mCRC.

Summary Immunological responses in human intestinal allografts are poorly understood and accurate diagnosis of acute cellular rejection remains difficult. Here, human intestinal allografts were analyzed by multi-color quantitative fluorescent immunohistochemical morphometry in order to monitor the clinical course of rejection. Morphometry gave two-dimensional plots based on size and circularity, and identified phenotypes of individual cells infiltrating the allograft by fluorescent staining. Using this method, invariant TCRVα24+ NKT (iNKT) cells were observed in the intestinal allograft during rejection. Because these were not identified in the normal donor intestine before surgery, this finding was considered to be a signature of acute cellular rejection of the intestinal allograft. Infiltrating iNKT cells released IL-4 and IL-5, Th2-related cytokines that antagonize the Th1 responses that induce acute cellular rejection. Histological observation suggested eosinophilic enteritis in the mucosa with elevation of IL-4 and IL-5. In conclusion, iNKT cells were recruited to the intestine; however, because higher levels of IL-4 and IL-5 may contribute to eosinophilic enteritis, timely steroid administration is recommended for allograft injury due to enteritis, as well as acute cellular rejection.

We have characterized the electrical and optical activities of small grain boundaries (SA-GBs) by using electron-beam-induced current (EBIC) and cathodoluminescence (CL). EBIC observation at room temperature indicates that the SA-GBs are grouped into two categories. SA-GBs with misorientation angle lower than 1° shows lower EBIC contrast like

症例は78歳，女性．大腸癌術後2週間目に腹部膨満を主訴として来院．腸閉塞を疑って施行した腹部CTで大腸の壁肥厚および脾彎曲から下行結腸にかけての著明な拡張を認め，中毒性巨大結腸症と診断．さらに大腸内視鏡で偽膜形成を認め，Clostridium difficile（CD）毒素陽性であったため劇症型CD腸炎が原因と判断した．全身状態も安定していたため初期には保存的加療を選択したが，入院後4日目にDICを併発し緊急で結腸全摘術および回腸瘻造設を施行した．術後経過は良好で特に合併症なく術後28日目に退院となった．劇症型CD腸炎は手術を考慮する必要があるが，下痢症状を伴わない場合は早期診断が困難な場合もある．今回は迅速に診断し救命しえた劇症型CD腸炎を経験したため文献的考察を含め報告する．

完全内臓逆位症を伴った胆石症に対する腹腔鏡下胆嚢摘出術を経験した．症例は65歳，男性．心窩部痛を主訴に発症し，胆嚢内には多数の結石を認めた．肝・胆嚢は左側にあり，通常位とは完全に左右対称の鏡面する部位に位置していた．胆道3D-CTでは胆嚢管から胆嚢内への造影剤の流入はないものの，胆道系の走行に変位は認めなかった．手術は臍直下に腹腔鏡用ポート，ワーキングポートは3本で，左中鎖骨線上では肋弓下から7cm足側に離して留置した．胆嚢を厚く覆っていた大網を慎重に剥離したのちcritical viewを露出，確認したうえで胆嚢動脈，胆嚢管をそれぞれクリップ後に切離した．両手を用いるdouble hand法で行ったが，左手での剥離操作を必要とする場面が多かった．経過は順調で術後2日目に退院された．今回，完全内臓逆位での腹腔鏡下胆嚢摘出術を経験したが，右手操作のみならず左手操作にも習熟しておくことが手術を安全に完遂するうえで重要であると思われた．

Background Among patients with adhesive small bowel obstruction (ASBO) initially managed with a conservative strategy, predicting risk of operation is difficult. Methods We investigated ASBO patients at 2 different periods to derive and validate a clinical prediction model for risk of operation. Results One hundred fifty-four patients were enrolled into the derivation cohort and 96 into the validation cohort. Based on the derived scoring, including age ≥65 years, presence of ascites, and gastrointestinal drainage volume >500 mL on day 3, each patient was classified into 1 of 4 risk classes from low risk to high risk. When applied to the validation cohort, the positive predictive value (PPV) for operation in the high-risk class was 72%, while the negative predictive value (NPV) in the low-risk class was 100% with high sensitivity (100%) and specificity (96%). Conclusions The prediction model performs well for risk stratification of need for surgical intervention following conservative strategy among ASBO patients.

症例は59歳の男性で，既往に直腸癌，ベーチェット病，ホジキンリンパ腫，上行結腸癌がある．胃癌に対して胃切除術を施行した際に，横行結腸に3 cm大の腫瘤性病変を認めたため合併切除を行った．病理組織学的検査結果は筋線維芽細胞性腫瘍であった．術後7か月目より右季肋部痛が出現し，腹部CTにて肝臓に多発低吸収域が認められた．肝生検の結果，筋線維芽細胞性腫瘍の肝転移と考えられた．肝転移巣の進行抑制を目的に，Mitomycin CとDegradable starch microspheresを用いた肝動注療法を週1回7コース施行したが，術後14か月目に肝不全にて死亡した．

目的: 大腸癌術後症例に対するProbioticsの薬剤効果について検討．対象と方法: 再発，重篤な併存疾患を除く大腸癌術後201例に対してProbiotics服用の意思確認を行い，希望者80名を対象．ザ·ガード（納豆菌，乳酸菌含有）を3カ月間提供し，服用前後でアンケート調査を施行．QOLスコアとしてSF-36, EORTC QLQ-C30および排便機能に関する質問項目を使用．成績: 66名からアンケート回収．内訳は右側結腸癌18例，左側結腸癌23例，直腸癌22例．排便習慣の改善は63.5%，服用継続希望も61.9%と高かった．Probiotics服用後では排便回数，残便感の改善が見られ，QOLに関してもSF-36の社会生活機能，日常役割機能の2項目およびQLQ-C30のGlobal QOL, Constipation, Diarrheaの3項目で改善がみられた．結論: 大腸癌術後ではProbiotics服用により排便習慣の改善，QOLの向上が期待できる.

目的:末梢穿刺中心静脈カテーテル（以下PICC）は穿刺時の重篤な合併症が少なく，安全かつ簡便な静脈輸液路として有用と言われている．今回われわれは中心静脈カテーテル挿入に際しPICCを使用し，従来の中心静脈カテーテル（以下CVC）と比較し，挿入時および長期留置に伴う合併症について検討した．方法:2004年１月～12月に当科入院中，中心静脈カテーテル留置を必要とした160例（PICC 73例，CVC 87例）について挿入時および留置期間における合併症等をretrospectiveに解析した．結果:挿入時の合併症として気胸は両者ともなく，カテーテル留置平均日数およびカテーテル敗血症の発生に有意差はなかったが，カテーテル先端の位置異常（PICC 12.3％，CVC 1.1％）に有意差を認めた．考察:PICCは留置期間，感染に関してCVCと差はなく安全性は確認できたが，カテーテル先端の位置異常が多く，先端位置異常の改善につき今後の検討を要する．

Survival benefit of radical surgery for locally recurrent rectal cancer depends on whether disease is cured rather than whether death is delayed. Cured patients gain decades of life and are spared from sufferings with recurrence. Unfortunately, the majority of patients undergoing surgery, particularly those with extrarectal pelvic recurrence, have poor outcomes with occult disseminated disease. This study was designed to identify which of these patients are curable. Of 61 patients with pelvic recurrence treated by radical reexcision more than nine years before, 36 patients whose initial surgery was abdominoperineal resection were examined retrospectively. We used the logistic regression and Gamel-Boag regression models to estimate curability and identify predictors of cure. Ten patients survived five years and seven survived ten years. The cumulative disease-specific mortality curve leveled off 6.5 years after reexcision and remained at 74 percent (95 percent confidence interval, 60–89), indicating that the remaining 26 percent are curable. This value is comparable with the 23 percent curability estimated by the Gamel-Boag model, which also found that the disease-free interval from the initial surgery to the first recurrence is the best predictor of cure (P = 0.005). Of 11 patients with disease-free interval three years or more, 6 survived ten years, whereas 8 of 9 patients with disease-free interval less than one year died of second recurrence within three years of reexcision. Even patients with extrarectal pelvic recurrence may have isolated disease that is amenable to complete eradication. As a biologic marker, the disease-free interval serves to predict curability and may distinguish isolated disease from occult disseminated disease.

目的 : 鼠径ヘルニアに対するtension free repairは合併症・再発率とも低いことが報告されているが, 両側同時手術症例の検討は少ない. 今回両側ヘルニアの特徴および同時手術の安全性について検討した. 方法 : 1993年1月～2003年9月に治療された成人鼠径ヘルニア患者899症例 (A群 : 両側153例, B群 : 片側746例) を対象とし, 両群の特徴, 術後合併症, 再発率をretrospectiveに比較検討した. 結果 : 片側を主訴に来院した症例の10%に両側ヘルニアを認めた. ヘルニアのタイプはB群で外鼠径76%, A群で両側内鼠径45%, 両側外鼠径30%, 両側異なるタイプ25%であった. 術後入院期間 (A群 : 3.6日, B群 : 3.2日), 術後合併症 (1.9% vs 1.8%), 再発率 (メッシュ不使用例6.5% vs 3.9%, 使用例は両群とも0%) はいずれも両群に差を認めなかった. 結論 : 鼠径ヘルニアの診察では対側の有無の確認が重要で, 両側同時に手術することは安全である.

症例は78歳, 女性. 心窩部不快と悪心を認め他院受診し, 腹部CT検査にて膵頭部腫瘍疑われ当科受診となった. 主訴は心窩部不快と悪心. 身体所見にて臍右側に境界明瞭で可動性良好な腫瘤を触知した. 腹部超音波検査では膵頭部外側に後方エコーの増強を伴う68×43mm大の境界明瞭な充実性腫瘤を認めた. 腹部CT検査では膵頭部外側に辺縁および内部に不均一な造影効果を伴う径6.5cm大の境界明瞭な充実性腫瘤を認め, MRI検査ではT2強調像で不均一な高信号を示す腫瘤を認めた. 以上の所見より膵漿液性嚢胞腺腫, 十二指腸GISTを想定し手術施行した. 術中所見にて膵頭部に6cm大の弾性軟腫瘤を認めたため, 幽門輪温存膵頭十二指腸切除術施行し, 術後病理組織学的検索で漿液性嚢胞腺腫と診断された. 膵外へ発育し, 可動性のある腫瘤として認められた漿液性嚢胞腺腫は非常に珍しいと考えられたので文献的考察を加えて報告する.

症例は81歳, 男性. 主訴は黄疸, 褐色尿. 腹部超音波検査, 造影CT検査で膵頭部に径6cm大の多房性嚢胞様病変を認めた. 十二指腸への直接浸潤, 総胆管の拡張も疑われたが, 主膵管に拡張を認めなかった. 上部消化管内視鏡検査では十二指腸球部内腔に腫瘍が露出し, 多量の粘液を認めた. PTCDでは下部胆管に先細り状の狭窄を認め, 胆汁細胞診で腺癌と診断された. 以上の所見より, 膵粘液癌, 分枝型膵管内乳頭状粘液性腫瘍 (以下, 分枝型IPMT) 由来の浸潤癌などを想定し手術施行した. 術後病理組織学的検査で粘液結節の中に腺癌の胞巣を認め, 膵粘液癌と診断された. しかし, 術前検査では膵頭部から十二指腸に浸潤する造影効果の乏しい多房性腫瘍を認め, 腫瘍部の生検で多量の粘液と高円柱状, 粘液上皮様の細胞を認めており, 粘液癌と分枝型IPMT由来の浸潤癌の鑑別は困難であった.

Various transporters such as H+/peptide cotransporter PEPT1 are expressed in the intestine, and play important physiological and pharmacological roles in the body. Present study was performed to examine the expression profile of 20 kinds of transporters (PEPT1 and 2, P-glycoprotein, amino acid transporters and organic ion transporters) along the human digestive tract, especially focusing on PEPT1. Using normal mucosal specimens, real-time polymerase chain reactions were carried out. Immunoblot analyses were also performed for PEPT1 expression. PEPT1 mRNA was highly expressed in the small intestine (duodenum>jejunum>ileum) compared to other tissues, and some patients showed a significant level of expression in the stomach. The expressional pattern of PEPT1 in the stomach and histological diagnosis indicated that gastric PEPT1 originated from the intestinal metaplasia. The amino acid transporters showed unique mRNA expression levels and distributions in the digestive tract. For example, the expression levels of B(0)AT1, a Na+-dependent and chloride-independent neutral amino acid transporter, were increased from the duodenum to ileum, which pattern is completely inverted to that for PEPT1. There is little expression of organic ion transporters except for organic cation/carnitine transporter OCTN2. In conclusion, PEPT1 was abundantly expressed in the small intestine, and the reciprocal expression of PEPT1 and B(0)AT1 may serve for the efficient absorption of protein digestive products.

Purpose: Human invariant natural killer T (NKT) cells are novel, distinct lymphocyte populations with a restricted T-cell receptor repertoire (Vα24-Vβ11). They play a pivotal role in immunoregulation and in antitumor activities. This study focused on Vα24+ NKT cells in colorectal carcinomas and their clinicopathologic significance.Experimental Design: Vα24+ NKT-cell infiltration immunohistochemistry was studied in a total of 103 colorectal carcinoma cases. The degree of NKT-cell infiltration in tumors was evaluated as low (Results: A small number of Vα24+ NKT cells were found in the normal colorectal mucosa (2.6 ± 3.7 cells/5 HPF); however, their number increased remarkably in colorectal carcinomas (15.2 ± 16.3 cells/5 HPF; P = 0.0003) and a majority showed phenotype of activation. Higher NKT-cell infiltration was more frequent in women than in men (P = 0.034) and correlated with fewer lymph node metastases (P = 0.042). Patients with high NKT-cell infiltration showed higher overall (P = 0.018) as well as disease-free (P = 0.0006) survival rates. Intratumor NKT-cell infiltration was an independent prognostic factor for the overall (P = 0.033) and disease-free (P = 0.0064) survival rates.Conclusions: Increased infiltration of Vα24+ NKT cells was observed in colorectal carcinomas. Higher Vα24+ NKT-cell infiltration in colorectal carcinomas was an independent prognostic factor for favorable prognosis.

Although radiation enteritis is a well-recognized sequel of therapeutic irradiation, the standard surgical method is not universally agreed upon. Not only the short-term effect but also the long-term effect after a surgical intervention has been fairly well reported. To reassess the surgical therapy for radiation enteritis, we retrospectively analyzed 48 patients (5 males and 43 females, mean age 58.6 years) who had been operated on in our department. These patients were divided into two types according to the time of surgery or the clinical manifestation, and operative methods were analyzed. Patient's status such as bowel movement, body weight, and serum albumin value after surgery were analyzed, together with the patients survival. Our surgical methods were small intestinal resection for the intestinal obstruction, and pull-through reconstruction for proctitis. Two patients died of multiple organ failure caused by perforated peritonitis irrespective of emergent operation. Although the overall morbidity was 21.7%, there was no leakage when bowels were anastomosed. Overall survival after radiation-related complication in patients without previous neoplastic disease recurrence was 89%, 79%, and 69%, at 1, 3, and 5 years after surgery, respectively. Bowel motility, serum albumin level, and body weight recovered gradually soon after the operation and reached satisfactory levels within 6 months. Our analysis showed that small bowel injury should be treated by generous resection of the affected bowel followed by careful anastomosis of the disease-free ends, while rectal resection is best dealt with by restorative proctectomy. This may provide a good quality of life and minimize major postoperative complications such as leakage.

Objectives: Immature microvessels, which are not covered by pericytes, are irregular and leaky. We hypothesized that tumor cells can penetrate immature microvessels more easily than mature microvessels. In this study, we investigated the maturation of angiogenesis by the immunohistochemical staining of colorectal cancer specimens and determined the correlation between the microvessel count or the maturity of microvessels and clinicopathological variables. Methods: Ninety-two surgical specimens from our department were used. Double immunostaining of endothelial cells with anti-CD34 antibody and pericytes with anti-α-smooth muscle actin antibody was performed. The microvessel density (MVD) and microvessel pericyte coverage index (MPI) as an index of microvessel maturation were evaluated. Results: The MVD showed a significant positive correlation with tumor size, depth of invasion and Dukes’ stage. The MPI showed a significant positive correlation with the histological differentiation of the tumor tissues and distant metastasis at the time of operation. The high MVD group (≧26.0, n = 50) tended to have a poorer prognosis than the low MVD group (Conclusions: These findings demonstrate that immature neovascularization was observed in poorly differentiated tumors and was correlated with metastasis, resulting in a poorer prognosis. Taken together, not only microvessel density but also vascular maturation were crucial factors for colorectal cancer patients.

大腸全摘術を行った家族性大腸腺腫症 (FAP) 患者の経過観察で注意する点は, 十二指腸ポリープ, 特に発生率の高いVater乳頭部周辺のポリープの癌化である. 癌化に対して膵頭十二指腸切除を余儀なくされることもあるため, 予防的処置が必要とされる. 今回, 我々はFAPの大腸全摘術後, 残存する十二指腸ポリポーシスに対して膵温存十二指腸切除術 (PPTD) を施行した1例を経験した. 症例は40歳の男性で, FAPおよび併発した直腸癌に対して大腸全摘術を行った. 約4か月後に明らかとなった肝転移および密生する十二指腸ポリポーシス (管状腺腫) に対し, 肝右葉切除およびPPTD (B-I再建) を施行した. 術後, 縫合不全, 膵液漏, 胆汁漏などの合併症はなく, 食事摂取も良好で通常の日常生活に復帰できた. 根治性や機能予後につき長期の観察と評価が必要だが, PPTDはFAP の十二指腸ポリポーシスに対して有効な治療法であると考えられた.

Vascular endothelial growth factor (VEGF) plays a central role in tumour angiogenesis. In a mouse intramuscular tumour model using VEGF-transfected HT1080 human fibrosarcoma, we investigated the morphological features and patterns of remodelling in size-matched tumours. Compared with the control tumours (C group), the VEGF-transfected tumours (V group) showed vigorous neovascularization with larger vessels. Fenestrations and disruptions of endothelia were specific to the V group. Three types of vascular remodelling, i.e. sprouting, luminal division and intussusceptive microvascular growth, were present in both groups. Morphometric analyses revealed that mural cell coverage of the endothelial cells was significantly smaller in the V group compared with that in the C group (V group, 28.2 +/- 18.6%; C group, 41.6 +/- 21.1%; P < 0.0001). To determine the prevalence of remodelling patterns, the occurrences of abluminal and luminal processes on endothelial cell surfaces were quantified. Abluminal processes are defined as cytoplasmic protrusions of the abluminal membrane of endothelial cells, which can vary from tiny spurs to solid sprouts of the cell. On the other hand, luminal processes are defined as intraluminal protrusions of the endothelial cell membrane, including various membranous changes from filiform processes to rather thick cytoplasmic bulges. An abluminal process is thought to represent an initial morphological change in sprouting type angiogenesis, and a luminal process to be a sign of implementation of luminal division. The frequency of abluminal processes was significantly higher in the V group than in the C group (V group, 0.243 +/- 0.138/microm; C group, 0.114 +/- 0.101/microm; P < 0.0001). In contrast, the number of luminal processes on the endothelial cells per micrometre was statistically comparable between the groups (V group, 0.285 +/- 0.252/microm; C group, 0.309 +/- 0.236/microm, P = 0.381). These results indicate that sprouting is the main mode of VEGF-induced tumour angiogenesis.

The mechanism of brain metastasis is not well understood, but the affinity between cancer cells and neural tissues may be involved in the process. The aim of our study is to elucidate the involvement of neural cell adhesion molecule (NCAM) and therapeutic parameters in patients with brain metastasis from colorectal cancer.We retrospectively identified 17 patients with brain metastasis from colorectal cancer. Data were collected with regard to patients' characteristics, location, and stage of primary tumor, and extent and location of metastatic disease. NCAM histochemical staining was undertaken using a paraffin block, and compared with 56 Dukes C patients and 13 Dukes D patients.Neural cell adhesion molecule expression was significantly higher in the primary tumors of the brain metastasis patients than in the lesions of the Dukes C and Dukes D control groups (p = 0.0004). Patients whose tumor was managed by radiosurgery survived longer than patients who had had whole brain radiation or those who had been left untreated.The fact that NCAM expression was high in the primary tumors of brain metastasis patients suggests that the affinity of cancer cells to a particular organ is important for circulation-mediated metastasis. Controlling local tumors using radiosurgery is certainly going to play an important role in extending survival and improving the patient's quality of life (QOL).

Intraportal transplantation of islets is usually performed by a percutaneous, transhepatic catheterization technique for type 1 diabetic patients. We show here an easier method of islet implantation into the liver. An islet film was made using rat islet and was simply placed on the liver of a diabetic recipient rat. Histologic examinations revealed that the islets passed through the liver capsule within a week after the implantation, entered the liver parenchyma within 3 weeks, and were encircled with hepatocytes by day 222. Recipient rats were cured of diabetes; however nonimplanted control rats had high levels of blood glucose. The film-transplanted islets could provide adequate insulin to maintain stable blood glucose levels. This novel method requires little skill and no special instruments. This islet film approach may prove suitable for simple islet transplantation in clinical cases.

症例は78歳女性.主訴は右季肋部痛で,画像検査で肝門部に手拳大の腫瘍を認め,肝への直接浸潤を伴った胆嚢癌と術前診断された.血液検査では白血球が高値を示した.肝部分切除を伴う胆嚢摘出術が施行され,扁平上皮癌と病理診断された.術後9カ月目に肝転移をきたしたのと同時に白血球が再上昇したため, G-CSF産生腫瘍を疑い血中G-CSF値測定,および抗G-CSF抗体による腫瘍組織の免疫染色を行った.血中G-CSF値は正常の約3倍と高値で,かつ腫瘍細胞の細胞質に陽性所見を認めたことからG-CSF産生胆嚢癌と診断した.経過中白血球数, G-CSF値は病状進行とともに上昇した.追加した化学療法が奏効せず術後12カ月で死亡した.胆嚢G-CSF産生扁平上皮癌は稀であり,文献的考察を加え報告した.

Paraesophageal type or mixed type esophageal hiatal hernia causes intrathoracic prolapse or torsion of the greater portion of the stomach; the greater curvature comprises the highest position. The condition is called upsidedown stomach or intrathoracic stomach. To treat intrathoracic stomach, the hernia gate should be closed and the stomach should be fixed after it is placed in the abdominal cavity. The procedure requires laparotomy under general anesthesia or laparoscopic surgery. Recently, several studies have reported that percutaneous endoscopic gastrostomy (PEG) is useful for treating intrathoracic stomach. It is relatively difficult to endoscopically place the intrathoracic stomach in the abdominal cavity. We created a new method to place intrathoracic stomach in the abdominal cavity by inserting a gastric balloon, then move forward to the PEG procedure. The method is simple and the result is very satisfactory.

We created a novel surgical repair for intractable rectovaginal fistula and treated four patients who had previously undergone unsuccessful surgery. An X-shaped skin incision was made on the perineum, and then the rectum was carefully divided from the vagina. Defects of both the rectum and the vagina were closed with vertical mattress sutures. The external sphincter muscle also was approximated. The gluteus muscle was identified through another skin incision to the buttock, and cut at the attachment to the femur. Bilateral gluteus muscles were approximated at the midline of the perineum so that the vagina was sufficiently separated from the rectum. Established anorectal angle was 92.5 degrees (SD=6.4 degrees ). Mean resting pressure was 101.3 cm H2O (SD=13.1). All patients retained complete anal function without soiling. The unusual problem of erosion of the posterior vaginal wall with fistulation in a sexually active woman justifies greater efforts, and this surgical technique offers good prospects in this small group of patients.

A newly improved method for controlling blood glucose was compared with the standard model predictive controller under continuous glucose infusion. Continuous intravenous glucose infusion at rates of 50 or 100 mg/kg/hour was conducted on pancreatectomized dogs. An improved blood glucose control method using a combination of the proportional controller in the initial stage and the model predictive controller in the later stage was compared with the simple model predictive controller. The parameters of the controller were determined by identifying individual responses to the infused insulin during the first 60 minutes. The parameters of the proportional controller were changed at 60, 90, and 120 minutes to reflect the response to the infused insulin. The simple model predictive controller was able to reach the target level in the usual manner under the low infusion rate of glucose. However, under glucose infusion rates of 100 mg/kg/hour and more, it was difficult to reach the target level within 8 hours. In contrast, the improved system could reach the target level within 5 to 8 hours even under continuous glucose challenge. Addition of the modified proportional controller to the model predictive controller can stabilize the blood glucose control even under continuous glucose infusion.

症例は31歳の男性で, 平成9年頃からアルコール性膵炎の加療歴があり, 腹部CT検査では膵仮性嚢胞が指摘されていた. 平成12年2月3日に左上腹部痛のため入院. 腹部CT検査では, 膵尾部に直径約5cmの膵仮性嚢胞を認め, 嚢胞内脾門部寄りに造影効果のある径5mm大の腫瘤を認めた. 保存的治療により軽快したが, 3か月後に腹部CT検査を行ったところ, 膵仮性嚢胞の増大と嚢胞内に突出する脾仮性動脈瘤が疑われ, さらに嚢胞内への出血も疑われた. 5日後の腹部CT検査で動脈瘤の増大を認めたため, 血管撮影を行い, 脾仮性動脈瘤を確認した後, 同部の血管塞栓術を行った. 2週間後, 待期的に膵仮性嚢胞の根治術として動脈瘤を含めた膵体尾脾合併切除術を行い良好な結果を得ている.

We present here a case of chronic perianal pyoderma (CPP), who was treated with a novel skin graft. The patient was a 28-year-old male who had suffered from painful abscesses and nodules on his buttocks for over 10 years. Although the abscesses and nodules were initially restricted to one buttock, they gradually spread over both buttocks. He visited our hospital in July of 2000. He was clinically diagnosed as CPP and treated with oral doses of antibiotics. When admitted to our hospital in September of 2000, an anal fistula was also found. The operations for CPP and anal fistula were simultaneously performed. After the anal fistula treatment, the lesions of CPP were totally resected. In this procedure, we removed the epidermis and upper dermis from the excised CPP lesions and grafted them on the defects of the excised lesion. There has been no recurrence of the CPP. This operation procedure, which we call the "recycled skin graft method" is less invasive, because a donor site for the skin graft is unnecessary. We considered it to be as one of the effective treatments for CPP.

Functional genetic variants of DNA repair genes may alter the host DNA repair capacity, and thus influence efficiency of therapies. We genotyped eight potentially functional single nucleotide polymorphisms (SNPs) in genes (i.e. ERCC1, XPA, XPC, XPD and XPG) involved in the nucleotide excision repair (NER) pathway in 496 Japanese gastric cancer patients, and assessed overall survival and recurrence-free survival. The combined effects of risk genotypes of these eight SNPs in Japanese patients were further replicated in 356 North-American gastric cancer patients. In Japanese patients, we found that the XPC rs2228000 TT genotype was associated with shorter overall survival [hazards ratio (HR) = 1.75, 95% confidence interval (95% CI) = 1.07-2.86] and recurrence-free survival (HR = 2.17, 95% CI = 1.19-3.95), compared with CC/CT genotypes, and the XPG rs17655 CC genotype was associated with shorter overall survival (HR = 1.60, 95% CI = 1.08-2.36), compared with GG/CG genotypes. The number of observed risk genotypes in the combined analysis was associated with shorter overall survival and recurrence-free survival in a dose-response manner (P(trend) = 0.006 and P(trend) < 0.000) in Japanese patients; specifically, compared with those with ≤1 risk genotypes, those with ≥2 risk genotypes showed markedly shorter overall survival (HR = 1.79, 95% CI = 1.18-2.70) and recurrence-free survival (HR = 2.80, 95% CI = 1.66-4.73). The association between ≥2 risk genotypes and shorter overall survival was not significant (HR = 1.26, 95% CI = 0.82-1.94) in North-American patients, but the trends were similar in these two groups of patients. These data show that functional SNPs in NER core genes may impact survival in Japanese gastric cancer patients.

The MO-CVD method as a deposition process corresponding to the mass production of the high-quality ZnO film that can be used as an active layer in the thin film transistor is paid to attention. Bis(acetylacetonato) zinc(II) (Zn(acac)2) which has chemical stability and low toxicity is promising as the inexpensive raw material for CVD. The problem includes (1) pollution with water in process by character to easily take water of crystallization, and (2) the supply of the gas-phase raw material by sublimation should be not able to be controlled easily because it is a fine particle. In this study, Zn(acac)2 anhydrate fiber was prepared from Zn(acac)2 monohydrate powder by the sublimation process. Melting point of this fiber was almost same (∼134 °C) as the monohydrate powder in N2 atmosphere. ZnO film was deposited on r-face sapphire substrate by MO-CVD process using Zn(acac)2 anhydrate fiber, successfully. RMS of the film flatness was 0.48 nm. This film had resistivity of 4.6 × 10–1 Ω·cm, carrier electron density of 9.1 × 1017 cm–3 and Hall mobility of 15 cm2·V–1·s–1. (© 2010 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim)

PURPOSE: It has recently been demonstrated that the tumor growth rate is a stronger determinant of survival than the extent of the growth in local recurrence of rectal cancer. We studied which factors controlled the tumor growth rate using modern immunohistochemical methods. METHODS: In 51 patients who underwent extended resection for this condition, paraffin-embedded specimens were examined for 1) tumor angiogenesis by CD31 staining and microvessel counting, 2) apoptosis by terminal deoxynucleotide transferase-mediated deoxyuridine triphosphate-biotin nick end-labeling staining, and 3) cellular proliferative activity using anti-proliferative cell nuclear antigen antibody. The results were compared with carcinoembryonic antigen doubling time and survival. RESULTS: The five-year survival rate was 20 percent. The postoperative carcinoembryonic antigen doubling time, which was the strongest predictor of survival, correlated highly with proliferative cell nuclear antigen labeling index, but did not correlate with the apoptotic index or microvessel counts. CONCLUSION: Our study shows that cancer cell proliferation rather than apoptosis or angiogenesis is a major determinant of tumor growth rate and survival in patients with locally recurrent rectal cancer.

BACKGROUND It still is unclear when angiogenic potential, which is believed to be a prerequisite for tumor development, is acquired. The current study was designed 1) to clarify when the phenotypic change of angiogenicity occurs during the development of colon carcinoma and 2) to investigate the possible roles of vascular endothelial growth factor (VEGF) and p53 in angiogenesis. METHODS Colon carcinomas were classified according to the following criteria: m carcinomas were tumors in which carcinoma cells were observed within the mucosa (excluding adenomas with severe atypia) according to the World Health Organization criteria. sm carcinomas were defined by invasion into the submucosa but not into the muscularis propria. Using 27 adenomas, 26 m carcinomas, and 20 sm carcinomas, VEGF expression was analyzed with reverse transcriptase-polymerase chain reaction and immunohistochemistry. Microvessel density, VEGF, and p53 status were evaluated by immunohistochemistry. RESULTS Neither VEGF mRNA nor VEGF protein was detected in any of the mild-to-moderate dysplastic adenomas, whereas 16 of 26 m carcinomas (62%) and all sm carcinomas exhibited VEGF protein. The microvessel density in adenomas, m carcinomas, and sm carcinomas was 3 ± 0.55, 6.1 ± 1.12, and 12 ± 1.35 (0.739 mm2 per field), respectively. In m carcinomas, positive VEGF expression was coincident with the expression of p53, and stainability for both VEGF and p53 was similar with regard to spatial distribution in tumor tissues. In m and sm carcinomas, there was a statistically significant correlation between the intensity of VEGF expression and microvessel density. CONCLUSIONS The results of the current study demonstrated that angiogenesis develops in association with tumor progression from adenoma to noninvasive colorectal carcinoma, at least in part due to VEGF, and suggested that VEGF in m carcinomas is induced by mutant p53, although alternative mechanisms of VEGF up-regulation may exist in sm carcinomas. Cancer 2000;88:1820–7. © 2000 American Cancer Society.

BACKGROUND It has been suggested that tissue factor (TF) plays an important role in tumor metastasis. Its expression in sarcoma cells was reported to up-regulate the vascular endothelial growth factor (VEGF) gene and thereby enhance tumor angiogenesis, which is essential to tumor metastasis. Although many malignant tumors have been reported to express this protein constitutively, recent clinical studies have focused mainly on the correlations among TF expression, tumor progression, and histologic grade. Therefore, to address the role of TF and the underlying mechanism of hematogenous metastasis of colorectal carcinoma, the authors analyzed the correlations among TF expression, hepatic metastasis, and VEGF gene expression in surgical specimens. Furthermore, they analyzed the prognostic significance of TF expression with respect to overall patient survival. METHODS Expression of TF and VEGF genes in 67 advanced colorectal carcinoma specimens was studied by immunohistochemistry and Northern blot analysis, respectively. The correlations among TF expression, hepatic metastasis, and other factors were analyzed with univariate and multivariate statistics. Survival rates were calculated using the Kaplan–Meier method. RESULTS Univariate and multivariate analyses showed TF expression to be a significant (P = 0.0001) and independent risk factor for hepatic metastasis, whereas a weak but insignificant correlation was observed between TF and VEGF gene expression. The outcomes in the TF positive group were significantly worse in all cases (P = 0.0001) and in the cases without synchronous hepatic metastasis (P = 0.0156). CONCLUSIONS Although the precise mechanisms are unknown, TF expression is a suitable indicator of both hepatic metastasis and prognosis for colorectal carcinoma patients. Cancer 2000;88:295–301. © 2000 American Cancer Society.

Few studies have been conducted focusing on a potential role of reactive oxygen species in tumor cell metabolism. Here we studied human colorectal adenocarcinomas and adenomas to determine whether oxidative stress is imposed on cancer cells in vivo and used specific antibodies against 8-hydroxy-2'-deoxyguanosine (8-OHdG), 4-hydroxy-2-nonenal (HNE)-modified proteins, and 3-nitro-L-tyrosine (3-NT) to determine whether there is an association between oxidative stress and cellular proliferation. Higher levels of oxidative modifications in DNA and proteins were observed in carcinoma cells, but not in adenoma cells, than in the corresponding nontumorous epithelial cells by immunohistochemistry as well as high-performance liquid chromatography (HPLC)-based 8-OHdG determination. The fraction of proliferating cell nuclear antigen-positive cells was proportionally associated in adenocarcinomas with the staining intensities of 8-OHdG and 3-NT. Furthermore, Western blot analysis of the proteins extracted from carcinoma cells revealed several specific proteins modified by HNE or peroxynitrite. Thus we concluded that colorectal carcinoma, but not adenoma cells, are exposed to more oxidative stress than their corresponding nontumorous epithelial cells, regardless of clinical stage and histology, and further that the oxidative stress in carcinoma cells might stimulate cellular proliferation.