Shoji Nakamori

MUC1 mucin expression as a marker of progression and metastasis of human colorectal carcinoma.

BACKGROUND/AIMS The MUC1 mucin distributes among a variety of epithelial tissues (except the intestinal epithelia) and is often detectable in colorectal carcinoma tissues and cell lines. This study aimed to elucidate whether MUC1 mucin expression correlated to the progression of colorectal carcinomas. METHODS We collected 113 tissue specimens, including primary colorectal carcinoma, normal mucosa, liver metastases, lymph node metastases, and normal livers from 58 patients with colorectal carcinoma. Immunohistochemical staining and Western blotting analysis with mature MUC1 mucin-specific monoclonal antibodies were performed. RESULTS The levels of mature MUC1 mucins were significantly higher in carcinoma tissues than those in normal colonic mucosa (P < 0.001). Furthermore, the levels of mature MUC1 mucins were significantly higher in primary tumors from patients having metastasis or metastatic tumors than in primary tumors from patients without metastasis (P < 0.001). In the primary sites, mature MUC1 mucin levels apparently increased according to progression of the stages (P < 0.001). CONCLUSIONS These results strongly suggest that mature MUC1 mucins become ectopically expressed in colorectal carcinoma progressed to the metastatic stages and that mature MUC1 mucins may be a useful marker for advanced colorectal carcinoma.

Human colon carcinoma cells with increased invasive capacity obtained by selection for sialyl-dimeric Lex antigen

Sialyl-dimeric LeX antigen (NeuAc alpha 2-3Gal beta 1-4[Fuc-alpha 1-3] GlcNAc beta 1-3Gal beta 1-4[Fuc alpha 1-3]GlcNAc beta 1-R; SLX) is an oncodevelopmental carbohydrate antigen expressed both on glycolipids and on mucin-like glycoproteins in human colorectal carcinomas. The levels are higher in primary tumors at advanced stages than in tumors at early stages, and metastatic lesions contain a greater quantity of this antigen than corresponding primary tumors. To study whether this antigen influences the metastatic behavior of tumor cells, we selected SLX variant cells from the human colon carcinoma cell line KM12C using the specific monoclonal antibody FH6. We obtained two stable cell lines: a high expresser (KM12-HX) and a low expresser (KM12-LX) of this antigen. The growth rate of these cells are similar. A mucin-like glycoprotein reactive with monoclonal antibody FH6 was detected after electrophoretic separation of KM12-HX cell lysates but not of KM12-LX lysates. The degree of invasion was compared in assays in vitro using matrigel-coated filter membranes. The number of KM12-HX cells that invaded the membranes was significantly higher than KM12-LX cells.

Risk factors for bleeding in patients receiving fondaparinux after colorectal cancer surgery

Objective: The aim of this study was to identify risk factors for bleeding complications in patients who receive Venous thromboembolism (VTE) prophylaxis with fondaparinux (FPX) after colorectal cancer surgery. Methods: Records of 546 patients who underwent VTE prophylaxis with intermittent pneumatic compression and FPX after colorectal cancer surgery between January 2009 and May 2014 were reviewed. Patient characteristics, surgical procedures, and patient laboratory data were examined to identify risk factors for bleeding complications using univariate and multivariate logistic regression. Results: We reviewed the records of 324 males and 222 females. Median age and BMI were 68.5 years and 22.7 kg/m2, respectively. The number of laparoscopic surgeries was 366. Median operative time and blood loss were 188.5 min and 20 ml, respectively. The incidence (%) of bleeding events was 5.3%. In univariate analysis, age ≥80 years, BMI ≥25.0 kg/m2, hypertension, and antithrombotic therapy were associated with a significantly higher incidence of bleeding events. Multivariate analysis identified age ≥80 years (odds ratio 5.814; 95% confidence interval 2.502-13.278) as an independent risk factor. Conclusion: Age ≥80 is a risk factor for bleeding in patients who receive FPX for VTE prophylaxis after colorectal cancer surgery.

Extended Pancreatoduodenectomy for Adenocarcinoma of the Pancreatic Head

This chapter reviews the role of extended pancreatectomy in resection of adenocarcinoma of the pancreatic head. Because cancer cells are likely to spread into the lymph nodes and neighboring connective tissues, locoregional recurrence had been common in traditional or conventional pancreatectomy. Differing from the techniques in the conventional Whipple’s procedure, our extended pancreatectomy is characterized by skeletonizing the major vessels to clear a wide range of lymphatic and connective tissues. By this procedure, a significant improvement has been obtained in the long-term survival rates and the locoregional control. However, such a beneficial effect is limited to the less advanced tumors: these are less than 4 cm in diameter, nodal involvement is absent or limited in the n1 group, and cancer invasion to the portal vein is either absent or less than 2 cm in length and hemilateral. For more advanced cancers, this procedure seems to be of no use at present. In the future, however, we can expect to increase the long-term survival rate after an extended pancreatectomy and thereby widen its indication, when we combine more effective adjuvant therapy that can reduce both locoregional recurrence and liver metastasis.

Genetic Detection of Circulating Cancer Cells and Micrometastasis in the Lymph Node.

大腸癌細胞の分子生物学的特性を利用し, 血液中やリンパ節内の微小癌病巣の検出が遺伝子レベルで可能であるか検討した. 血液中癌細胞の検出は, 末梢血および腫瘍部位からの流出静脈血中でのサイトケラチン19および20遺伝子発現を指標として行い, リンパ節内の微小癌病巣の検出は, パラフィン包埋材料を用い, 原発巣と同一のK-ras, p53遺伝子変異がリンパ節において認められるかを検討した. その結果, 22例中4例の大腸癌患者で血液中癌細胞の存在が認められた.サイトケラチン免疫染色による細胞診は, 全例陰性であった. また, 病理組織学的にn (-) と診断された109例の大腸癌中20例のリンパ節に原発巣と同一遺伝子変異が検出され, うち13例に再発が認められた. 以上より, 分子生物学的手法を用いることにより, 従来の方法では検出されなかった微小癌細胞が証明され, その臨床応用の可能性が示された.

The State of the Art and Perspective in Treatment of Gastric Carcinoma with Reference to Depth of Invasion.

胃癌が漿膜に露出すると, リンパ節転移陽性率が80%を超え, 腹膜播種の危険性が高まり, 肉眼型4型では後腹膜への浸潤も出現する. 大動脈周囲リンパ節転移陽性例は予後不良で, 5年生存率は17.7%であった.積極的に郭清を行った症例でも予後改善はなく, 適応例の決定が必要である. 腹膜再発の予防として漿膜露出胃癌の手術時にmitomycin C 40mgを生理食塩水1,000mlに溶解し, 60分間閉鎖腹腔内に投与した. これはinvitroではInhibition Concentration 90 (IC90) を満足する投与法であるが, 臨床的には延命効果は認めたものの, 腹膜播種を抑制することはできず, より有効な治療法の開発が必要である. 4型胃癌は, 肉眼的に他臓器に癌浸潤を認めなくても18%に組織学的癌浸潤が陽性で, 局所を十分に摘除しうる超拡大手術法が必要で, Appleby法を伴った左上腹部内臓全摘術により, 浸潤硬化型腹膜再発を抑制し, 良好な遠隔成績が得られた.

Relationship Between Gastrin Receptor Values in Colorectal Cancer Tissues and Clinical Stage

We have measured gastrin receptor (GR) in cancer tissue and adjacent normal mucosa of the colon and rectum from 12 patients. GR was detectable in all cancer tissues, and in 11 of 12 normal mucosa. GR levels were higher in the colorectal cancer tissues (mean±SD; 7.7±7.7) than in colorectal mucosa (mean±SD; 3.6±3.3) (p<0.05). Negative relationship was implicated by the observation that the mean GR content in cancer tissue in Dukes’ stage C (6.8±3.0) was significantly (p<0.05) higher than that in stage D (2.4±0.8). However, no other significant correlation was found between GR content and other clinicopathologic factors (age, sex, serum levels of gastrin and carcinoembryonic antigen (CEA), macroscopic appearance, histologic differentiation, and serosal invasion in primary cancer lesions).

Sialyl Lewis-X Antigen Expression in Human Colorectal Carcinomas: Relationship Between Expression Level and Prognosis

Levels of sialyl Lewis-X antigen (SLX) in 132 human colorectal carcinomas were immuno-histochemically examined. The positive SLX staining for the primary tumors was significantly correlated with the depth of tumor invasion (p<0.05), the presence of lymphatic invasion (p<0.005) and lymph node metastasis (p<0.001), and tumor stage(p<0.001). Patients with colorectal carcinoma showing positive SLX staining had higher relapse rate (p<0.001) and poorer survival rate (p<0.001) after surgery. Multivariate analysis suggested that SLX expression was an independent prognostic factor in the patients with colorectal carcinomas. Careful follow-up and intensive postoperative therapy are required for the patients with an SLX-positive colorectal carcinoma.

Adjuvant Intraperitoneal High-Dose Chemotherpay with Mitomycin C in Patients with Primary Advanced Gastric Cancer

Gastric cancer patients (n=53) with peritoneal dissemination defined macroscopically or microscopically underwent resection of the stomach (n=29) or resection plus intraperitoneal chemotherapy using mitomycin C (MMC) (n=24). Forty mg MMC dissolved in 1000 ml saline was intraperitoneally administered and withdrawn 60 min later. This treatment schedule was found to be relevant in terms of attaining an intraperitoneal MMC concentration over IC50, 7.6 μg/ml for 60 min, which was determined from the in vitro colony formation assay using human gastric cancer cells. Two year overall survival of the patients treated with intraperitoneal chemotherapy (25 %) was significantly (p=0.03) higher than that of those without it (14 %). These results suggest that intraperitoneal chemotherapy is a useful adjuvant treatment for gastric cancer patients with peritoneal dissemination.