To elucidate the mechanisms of rapid progression of serous ovarian cancer, gene expression profiles from 43 ovarian cancer tissues comprising eight early stage and 35 advanced stage tissues were carried out using oligonucleotide microarrays of 18 716 genes. By non-negative matrix factorization analysis using 178 genes, which were extracted as stage-specific genes, 35 advanced stage cases were classified into two subclasses with superior (n = 17) and poor (n = 18) outcome evaluated by progression-free survival (log rank test, P = 0.03). Of the 178 stagespecific genes, 112 genes were identified as showing different expression between the two subclasses. Of the 48 genes selected for biological function by gene ontology analysis or Ingenuity Pathway Analysis, five genes (ZEB2, CDH1, LTBP2, COL16A1, and ACTA2) were extracted as candidates for prognostic factors associated with progression-free survival. The relationship between high ZEB2 or low CDH1 expression and shorter progression-free survival was validated by real-time RT-PCR experiments of 37 independent advanced stage cancer samples. ZEB2 expression was negatively correlated with CDH1 expression in advanced stage samples, whereas ZEB2 knockdown in ovarian adenocarcinoma SKOV3 cells resulted in an increase in CDH1 expression. Multivariate analysis showed that high ZEB2 expression was independently associated with poor prognosis. Furthermore, the prognostic effect of E-cadherin encoded by CDH1 was verified using immunohistochemical analysis of an independent advanced stage cancer samples set (n = 74). These findings suggest that the expression of epithelial-mesenchymal transition-related genes such as ZEB2 and CDH1 may play important roles in the invasion process of advanced stage serous ovarian cancer. (Cancer Sci 2009; 100: 1421-1428) T he serous type, comprising approximately 50% of ovarian cancers, is the most aggressive histology and has a tendency to be detected as advanced stage at the time of diagnosis. (1,2) Patients with advanced stage serous ovarian cancer are managed with surgical cytoreduction followed by platinum and taxane-based chemotherapy. Serous ovarian cancer is moderately chemosensitive and initially responds to postoperative chemotherapy, but the survival of patients with advanced stage remains poor. Because the majority of early stage ovarian cancers are asymptomatic and there is as yet no reliable screening test, it is difficult to diagnose early stage serous ovarian cancer. Therefore, the molecular mechanisms of progression in serous ovarian cancer should provide valuable clues for early detection and improved prognosis.The development of microarray technology permits analysis of the expression levels of thousands of genes in cancer cells, and several studies have shown that microarrays can be used to identify gene expression profiles associated with surgery outcome, response to chemotherapy, grade, and survival in ovarian cancers.(3-17) However, there are limited reports of microarray analysis on tumor progression. (18)(19)(20) Serous o...

BackgroundAdvanced-stage ovarian cancer patients are generally treated with platinum/taxane-based chemotherapy after primary debulking surgery. However, there is a wide range of outcomes for individual patients. Therefore, the clinicopathological factors alone are insufficient for predicting prognosis. Our aim is to identify a progression-free survival (PFS)-related molecular profile for predicting survival of patients with advanced-stage serous ovarian cancer.Methodology/Principal FindingsAdvanced-stage serous ovarian cancer tissues from 110 Japanese patients who underwent primary surgery and platinum/taxane-based chemotherapy were profiled using oligonucleotide microarrays. We selected 88 PFS-related genes by a univariate Cox model (p<0.01) and generated the prognostic index based on 88 PFS-related genes after adjustment of regression coefficients of the respective genes by ridge regression Cox model using 10-fold cross-validation. The prognostic index was independently associated with PFS time compared to other clinical factors in multivariate analysis [hazard ratio (HR), 3.72; 95% confidence interval (CI), 2.66–5.43; p<0.0001]. In an external dataset, multivariate analysis revealed that this prognostic index was significantly correlated with PFS time (HR, 1.54; 95% CI, 1.20–1.98; p = 0.0008). Furthermore, the correlation between the prognostic index and overall survival time was confirmed in the two independent external datasets (log rank test, p = 0.0010 and 0.0008).Conclusions/SignificanceThe prognostic ability of our index based on the 88-gene expression profile in ridge regression Cox hazard model was shown to be independent of other clinical factors in predicting cancer prognosis across two distinct datasets. Further study will be necessary to improve predictive accuracy of the prognostic index toward clinical application for evaluation of the risk of recurrence in patients with advanced-stage serous ovarian cancer.

OBJECTIVES In this study, we investigated the early and midterm outcomes of initial watch-and-wait strategy for Stanford type A intramural haematoma and acute aortic dissection with thrombosed false lumen of the ascending aorta in patients with a maximum aortic diameter of ≤50 mm, pain score of ≤3/10 and no ulcer-like projection in the ascending aorta. METHODS Inpatient and outpatient records were retrospectively reviewed. RESULTS Of the 81 patients with type A intramural haematoma and acute aortic dissection with the thrombosed false lumen of the ascending aorta between April 2011 and April 2019, a watch-and-wait strategy was selected in 46 patients. The mean age of the patients was 68 years, and 22 (48%) patients were female. Ten patients underwent emergency pericardial drainage for cardiac tamponade at the time of presentation and 8 patients underwent aortic repair during hospitalization for new ulcer-like projection, re-dissection or rupture. In-hospital mortality occurred in 2 (4%) patients. During follow-up, survival at 1 and 2 years was 95% and 92%, respectively. There was no significant difference in survival or aortic events between patients in whom the watch-and-wait strategy and emergency surgical treatment were indicated. CONCLUSIONS The early and midterm outcomes of the initial watch-and-wait strategy were favourable for type A intramural haematoma and acute aortic dissection with the thrombosed false lumen of the ascending aorta in Japanese patients with a maximum aortic diameter of ≤50 mm, pain score of ≤3/10 and no ulcer-like projection. Further study is required to show the safety of this strategy.

Background: Given the exponential growth in cardiac device implantations, the need for less invasive lead extraction is increasing. The Excimer laser was approved for lead removal in Japan in 2010. The present study reports the initial experience using this novel technique to extract chronically implanted pacemaker and implantable cardioverter defibrillator (ICD) leads from Japanese patients. Methods and results: We performed a retrospective study of consecutive patients undergoing lead extraction using the laser sheath at a single Japanese center. Patient and lead characteristics, indications, and outcomes were analyzed. From August 2010 to September 2012, a total of 70 leads, including 14 ICD leads, were removed using the laser sheath from 40 patients (26 male, 14 female; age 65.5 ± 18.3 [mean ± SD] years; body mass index 21.8 ± 3.5 kg/m 2). The median implant duration was 87 months (range 13-328 months). Indications were infection (n = 35), venous occlusion (n = 4), and pain (n = 1). The femoral approach was used in combination with the laser technique in five cases. Complete procedural success was achieved with 68 leads (97.1%). Although the electrode tip was left behind in the remaining two leads, the desired clinical outcomes could be achieved; which were defined as clinical success. No cases resulted in failure. There were no major complications, including death and bleeding requiring open-chest surgery. Conclusions: Laser sheaths appear to provide a feasible and effective means of extracting chronically implanted pacemaker and ICD leads in Japanese patients.

Sclerosing encapsulating peritonitis (SEP) is characterized by the diffuse appearance of marked sclerotic thickening of the peritoneal membrane. We experienced a case with SEP accompanied by regional changes of peritoneum. A 37-year-old woman with end-stage renal failure was started on continuous ambulatory peritoneal dialysis in 1985 and was transferred to hemodialysis in 1997. She was admitted because of ileus in 1998 with SEP and died of septicemia. The diagnosis of SEP was confirmed via the autopsy. The root of the mesentery was retracted and shortened. Since the peritoneal change was marked in the regions with free margin of mesentery and was less apparent in the regions not adhered to mesentery, it is indicated that mechanical stress also contributes to the occurrence of SEP. Since calcification and ossification were only seen in a free margin of small bowel from mesentery, it is suggested that there is a close relationship between calcification and ossification. Since fibrosis invaded into the muscle layer, dysfunction of bowel movement as well as bowel obstruction contributed to the appearance of ileus. It is suggested that mechanical stress by the root of mesentery which is retracted and shortened also contributes to the appearance of SEP.