BACKGROUND To identify the role of survivin, a novel inhibitor of apoptosis (IAP) in colorectal tumorigenesis, the authors investigated tissue expression of survivin in human colorectal tumors including 43 hyperplastic polyps, 171 adenomas with low dysplasia, 42 adenomas with high dysplasia, and 60 carcinomas in adenoma, and examined whether the expression of survivin correlated with tumor cell apoptosis, proliferation, and angiogenesis, which is known to initiate the imbalance between cell proliferation and apoptosis. METHODS Immunohistochemical staining for the paraffin sections by using the monoclonal antibodies, survivin, p53, bcl‐2, Ki‐67, and CD34, was performed by the standard avidin‐biotin‐peroxidase technique. The apoptotic cells were detected by terminal deoxynucleotidyl transferase–mediated dUTP‐biotin nick end labeling method, using an Apop Tag in situ detection kit. RESULTS The immunoreactivity of survivin significantly increased in the transition from adenoma with low dysplasia to high dysplasia/carcinoma (P < 0.001). Similar changes in protein expression were observed for p53 but not for bcl‐2, which was expressed throughout the colorectal tumorigenesis. This transition was associated with a significant decrease in the apoptotic index (AI) and significant increases in the Ki‐67 labeling index (LI) and microvessel density (MVD; P < 0.001 for both). The expression of survivin inversely correlated with AI and was positively correlated with Ki‐67 LI and MVD (P < 0.001 for both). CONCLUSIONS These results suggest that, like p53, survivin plays an important role in transition from adenoma with low dysplasia to high dysplasia during human colorectal tumorigenesis. Cancer 2001;91:2026–32. © 2001 American Cancer Society.

DCs are the most potent antigen-presenting cells that play a major role in initiating the antitumor immune response. Although the clinical significance of TIDCs has been investigated in a variety of human cancers, few studies have focused on the in situ maturation status of DCs. We have analyzed the maturation-specific significance of TIDCs in the prognosis of patients with breast carcinoma. We evaluated 130 breast carcinomas for the presence of TIDCs using immunohistochemistry with an anti-CD1a antibody for immature DCs and an anti-CD83 antibody for mature DCs. Intratumoral expression of immunosuppressive cytokines was also examined. All samples contained CD1a ؉ TIDCs, and 82 (63.1%) samples contained CD83 ؉ TIDCs. The number of CD83 ؉ TIDCs was inversely correlated with lymph node metastasis and with tissue expression of VEGF and TGF-␤, whereas the number of CD1a ؉ TIDCs was not. Kaplan-Meier analysis (log rank statistics) revealed a significant association of increasing number of CD83 ؉ TIDCs with longer relapsefree (p ‫؍‬ 0.002) and overall (p < 0.001) survival. Furthermore, among patients with lymph node metastasis, the survival rate of those with larger numbers of CD83 ؉ TIDCs was significantly better than that of patients with fewer CD83 ؉ TIDCs. Multivariate analysis revealed that CD83 ؉ TIDCs had independent prognostic relevance in breast carcinomas. The infiltration of tumors by mature DCs expressing CD83 may be of great importance in initiating the primary antitumor immune response and is confirmed as an independent, immunologic prognostic parameter for survival in patients with breast cancer.

We determined the molecular mechanisms that regulate the pathogenesis of malignant pleural effusion (PE) associated with advanced stage of human, non-small-cell lung cancer. Intravenous injection of human PC14 and PC14PE6 (adenocarcinoma) or H226 (squamous cell carcinoma) cells into nude mice yielded numerous lung lesions. PC14 and PC14PE6 lung lesions invaded the pleura and produced PE containing a high level of vascular endothelial growth factor (VEGF)-localized vascular hyperpermeability. Lung lesions produced by H226 cells were confined to the lung parenchyma with no PE. The level of expression of VEGF mRNA and protein by the cell lines directly correlated with extent of PE formation. Transfection of PC14PE6 cells with antisense VEGF165 gene did not inhibit invasion into the pleural space but reduced PE formation. H226 cells transfected with either sense VEGF 165 or sense VEGF 121 genes induced localized vascular hyperpermeability and produced PE only after direct implantation into the thoracic cavity. The production of PE was thus associated with the ability of tumor cells to invade the pleura, a property associated with expression of high levels of urokinase-type plasminogen activator and low levels of TIMP-2. Collectively, the data demonstrate that the production of malignant PE requires tumor cells to invade the pleura and express high levels of VEGF/VPF.

Proximal gastrectomy for early upper-third gastric cancer can be performed safely with an excellent cure rate. This procedure deserves further clinical evaluation to assess patients' quality of life.

Our investigation clearly shows the effectiveness and importance of wide range lymph node dissection defined as D3 according to the Japanese N-grouping system for thoracic esophageal cancer. The three-field lymphadenectomy is regarded as a standard procedure for upper and middle thoracic esophageal cancer.

We have developed a new technique to resect hepatic parenchyma without inflow occlusion by using the Cavitron Ultrasonic Surgical Aspirator (CUSA) and bipolar cautery with a saline irrigation system. The significance of this method in hepatectomy was analyzed in comparison with historical control of hepatectomy using Pringle's maneuver. An ordinary bipolar cautery was remodeled with an infusion line to bring saline droplets down the inner surface of one arm of the tweezers through an opening about 1.5 cm proximal to its tip. The optimal flow rate of saline was approximately one drop per second. The power of bipolar cautery was adjusted to 50 watts. When the tweezer blades were approximated to 1 or 2 mm, saline droplets were directed to the tip of tweezers and could be immediately evaporated. After sonicating parenchymal cells, the tissue of small branches of Glisson's tree or small tributaries of the hepatic vein were coagulated by bipolar cautery. The coagulated cords were then easily cut by scissors. The impact of this technique on ordinary liver resections was evaluated by analyzing the postoperative clinical course in relation to the hepatic functional reserve necessary for major hepatectomy, duration of hepatectomy, and intraoperative blood loss. Hepatic resection without vascular occlusion using this technique could decrease the morbidity in patients who have less hepatic functional reserve. It could also decrease intraoperative blood loss. This new technique effectively decreased the surgical load of the remnant liver during parenchymal resection by avoiding ischemic stress. Consequently it extends the safety limits of major hepatectomy.

Rebamipide increased mucin-like substances on the cornea and conjunctiva of N-acetylcysteine-treated eyes. In accordance with the mucin-increasing effects, rebamipide improved the rose Bengal scores for the cornea and conjunctiva of N-acetylcysteine-treated eyes. However, the relevance of these findings to dry eyes is unclear because it is not known whether the change in mucus expression in the N-acetylcysteine model is similar to what occurs in aqueous tear deficiency. Consequently, it may be worth trying on an animal model of keratoconjunctivitis sicca.

Sarcopenic obesity is an independent risk factor for the development of SSI after LTG.