食道扁平上皮癌におきてエンドセリンB受容体の高発現は腫瘍の血管新生と予後に関与する

BACKGROUND:The endothelin axis has been shown to have a pivotal role in several human malignancies. The aim of this study was to clarify the clinical importance of endothelin receptor type B (ETBR) in human oesophageal squamous cell carcinoma (OSCC). METHODS:We evaluated ETBR expression in 107 patients with OSCC by immunohistochemistry. Microvessel density (MVD) and lymphatic vessel density were assessed by CD31 and D2-40 immunostaining, respectively. Furthermore, CD4, CD8, and CD45RO+ tumour-infiltrating lymphocytes (TILs) were immunohistochemically analysed.RESULTS:Sixty-one (57%) cases showed high expression of ETBR. Endothelin receptor type B expression was correlated with several clinicopathological factors including tumour differentiation, tumour depth, and lymph node metastasis. The overall and disease-specific survival rates were significantly lower in patients with high ETBR expression than patients with low expression. Furthermore, multivariate analysis revealed that ETBR status was an independent prognostic factor for patient survival. Mechanistic analysis indicated that MVD was significantly higher in tumour tissues with high ETBR expression compared with those with low expression, suggesting that angiogenesis may be a key mechanism in tumour progression and metastasis of OSCC mediated by ETBR expression. By contrast, there were no significant correlations between TILs and ETBR expression.CONCLUSION: Endothelin receptor type B has a pivotal role in oesophageal cancer and may be therapeutic target for this intractable malignancy.博士（医学）・乙第1336号・平成26年5月28

The prognostic significance of tumour-stroma ratio in endometrial carcinoma.

Background: High tumour stromal content has been found to predict adverse clinical outcome in a range of epithelial tumours. The aim of this study was to assess the prognostic significance of tumour-stroma ratio (TSR) in endometrial adenocarcinomas and investigate its relationship with other clinicopathological parameters. Methods: Clinicopathological and 5-year follow-up data were obtained for a retrospective series of endometrial adenocarcinoma patients (n = 400). TSR was measured using a morphometric approach (point counting) on digitised histologic hysterectomy specimens. Inter-observer agreement was determined using Cohen’s Kappa statistic. TSR cut-offs were optimised using log-rank functions and prognostic significance of TSR on overall survival (OS) and disease-free survival (DFS) were determined using Cox Proportional Hazards regression analysis and Kaplan-Meier curves generated. Associations of TSR with other clinicopathological parameters were determined using non-parametric tests followed by Holm-Bonferroni correction for multiple comparisons. Results: TSR as a continuous variable associated with worse OS (P = 0.034) in univariable Cox-regression analysis. Using the optimal cut-off TSR value of 1.3, TSR-high (i.e. low stroma) was associated with worse OS (HR = 2.51; 95 % CI = 1.22–5.12; P = 0.021) and DFS (HR = 2.19; 95 % CI = 1.15–4.17; P = 0.017) in univariable analysis. However, TSR did not have independent prognostic significance in multivariable analysis, when adjusted for known prognostic variables. A highly significant association was found between TSR and tumour grade (P < 0.001) and lymphovascular space invasion (P < 0.001), both of which had independent prognostic significance in this study population. Conclusions: Low tumour stromal content associates with both poor outcome and with other adverse prognostic indicators in endometrial cancer, although it is not independently prognostic. These findings contrast with studies on many - although not all - cancers and suggest that the biology of tumour-stroma interactions may differ amongst cancer types

Improvement of the multimodality treatment of oesophageal cancer

Ewout Courrech Staal beschrijft diverse onderzoeken gericht op het verbeteren van de multidisciplinaire behandeling van slokdarmkanker. In het eerste deel van zijn proefschrift staan chemoradiotherapie en chirurgie centraal. In deel twee richt Courrech Staal zich op het gebruik van biomarkers in de behandeling van slokdarmkanker. In het derde en laatste deel komen kwaliteitsaspecten in de behandeling van slokdarmkanker aan de orde

In reply to Hynes et al

Surgical oncolog

Health-related quality of life in long-term esophageal cancer survivors after potentially curative treatment

ObjectiveClinical outcomes have been investigated extensively in studies of esophageal cancer treatment. Less is known about long-term health-related quality of life outcomes. The aim of this study was to assess a range of health-related quality of life outcomes in patients with esophageal cancer treated with potentially curative intent at least 1 year earlier.MethodsBetween January 1995 and December 2007, 163 consecutive patients with cancer of the esophagus underwent a potentially curative treatment. All patients with a minimal follow-up of 1 year and without tumor recurrence were eligible. Questionnaires included the European Organization for Research and Treatment of Cancer core questionnaire (QLQ-C30), the European Organization for Research and Treatment of Cancer esophageal cancer-specific questionnaire (QLQ-OES18), and additional questions concerning survivorship issues.ResultsThirty-seven patients met the inclusion criteria, of whom 36 completed the questionnaires. Twenty-one patients had received neoadjuvant therapy followed by surgery, 9 patients had undergone surgery only, and 6 patients had chemoradiation only. Median survival was 54 (range, 16–162) months. In general, patients reported better health-related quality of life than a reference sample of patients with esophageal cancer, but somewhat compromised health-related quality of life compared with a reference sample of individuals from the general population. Although some symptoms continued to persist, patients' overall evaluation on their treatment, employment status and finances, body weight and image, and survivorship issues was positive.ConclusionsPatients who survive 1 year or more after potentially curative treatment for esophageal cancer can lead satisfactory lives. The results of this study can be used when informing patients with esophageal cancer about the long-term effects of treatment