Although highly refined endoscopes have made it possible to detect not only early gastric cancers with morphological changes, but also flat-type tumors (type IIb) on the basis of the color changes observed in them, the factors responsible for color changes in type IIb carcinomas have not been fully elucidated. The aim of this study was to analyze the potential mechanisms underlying these color changes.Thirteen type IIb cancers were selected from a total of 589 resected gastric cancers detected preoperatively using endoscopic examination. All of the tumors showed color changes alone, without surface changes, and the color changes included redness, discoloration, and spotty bleeding. Detailed histological examination of the resected stomachs revealed twelve more II b lesions that had not been identified at endoscopy. The endoscopic appearance of the IIb cancers were correlated with the degree of tumor differentiation, the extent of wall infiltration, and the number of capillaries.In cases that were detectable by endoscopy, the endoscopic color appearance correlated significantly with both tumor size (P < 0.02) and with the extent of mucosal cancer infiltration (P < 0.02). Histological examination of the IIb lesions revealed that redness and discoloration were significantly more frequent in the differentiated and undifferentiated cancer types, respectively (P < 0.01). There was a significant difference in the number of capillaries between type IIb carcinoma and the adjacent normal mucosa, but not between cancers. The numbers for differences in redness and discoloration were 7.0 +/- 5.6 and -14.0 +/- 8.8, respectively.These results suggest that the main factor underlying color change in type IIb early gastric cancers may be the number of capillaries in the lesions, in comparison with the adjacent mucosa. Whether the lesion is visible on endoscopy, however, depends more on its size than on the number of capillaries.
4065 Background: For assessments of tumor response in upper gastrointestinal cancers, Japanese criteria (JPN), which needs X-ray or endoscopic findings for primary lesion, has been generally used in Japan instead of international RECIST or WHO criteria. To compare the inter-criteria reproducibility of these radiological assessments, we analyzed the datasets of tumor responses from two phase III trials. Methods: A total of 115 gastric cancer patients in two treatment arms of JCOG9205, 5-FU and 5-FU plus cisplatin, and 103 esophageal cancer patients in a neoadjuvant 5-FU plus cisplatin arm of JCOG9907 were eligible for this analysis. Overall response rates (ORR) were calculated according to each of three criteria. The tumor responses, furthermore, were divided into four categories (CR, PR, SD, PD), following estimation of kappa statistics between two criteria as agreement measure. Results: As shown in the Table , ORR according to RECIST and WHO were very similar in both cancers. JPN tended to estimate higher ORR comparing to RECIST or WHO, particularly in esophageal cancer. In gastric cancer, kappa for concordance to RECIST were 0.92 for WHO and 0.86 for JPN. While in esophageal cancer, kappa were 0.72 for WHO and 0.40 for JPN. Conclusions: In these trials for gastric cancer and esophageal cancer, there was fairly consistent reproducibility between unidimensional RECIST and bidimensional WHO criteria. JPN criteria, depending on assessment of primary lesion, may give higher ORR particularly in esophageal cancer, and cautious interpretation may be necessary when evaluating ORR from Japanese trials using JPN criteria (Table). Overall response rates of respective treatment arms calculated according to RECIST, WHO and JPN criteria. [Table: see text] No significant financial relationships to disclose.
In this study, we aimed to develop a histological grading system for ovarian clear cell adenocarcinoma (CCA), based on the tumor growth architectures. Cases were defined as Group A if ≥90% of a tumor examined was composed of well-differentiated tubulocystic and/or papillary architectures; Group C if at least 10% of the tumor was composed of very poorly differentiated histology (i.e. solid masses or individual infiltrating tumor cells with no or little glandular/papillary differentiation); and tumors not corresponding to the first 2 descriptions were defined as Group B. The interobserver reproducibility and prognostic value of the assigned groups were analyzed for 159 CCAs from 5 institutions. The level of agreement in assigning the groups between 2 pathologists was 88.7% (=0.82). After consensus was reached, 46 (29%), 79 (50%), and 34 (21%) tumors were classified in Groups A, B, and C, respectively. In early-stage cases [International Federation of Gynecology and Obstetrics (FIGO) stage I–II], Group A tumors had significantly better outcomes (100% 5-yr survival) than Group B tumors (82% 5-yr survival, P=0.024 by log-rank test) or Group C tumors (56% 5-yr survival, P=0.00054 by log-rank test). Moreover, early-stage Group B tumors had significantly better outcomes than Group C tumors (P<0.001 by a generalized Wilcoxon test). In advanced cases (FIGO stage III–IV), Group A tumors had significantly better outcomes than Group C tumors (52% vs. 16% 5-yr survival, respectively, P=0.043). Group A and C tumors defined with our system were identified to have favorable and unfavorable prognostic factors, respectively, independent of the clinical stage of the disease and presence of residual tumors after the initial surgery. The proposed grouping system could divide patients with CCA into 3 subgroups with distinct prognostic indications, providing a 3-tier histological grading system for ovarian CCA.
Progression-free survival is an often-used endpoint in clinical trials comparing preoperative therapy and surgery-first therapy. Because the surgery date is always later in the preoperative arm than in the surgery-first arm, it is difficult to define progression-free survival optimally. We evaluated three progression-free survival definitions that used different methods to handle incomplete resection. The three definitions specify the event date of incomplete resection (IR) as follows: ‘IR = event’ method, date of surgery; ‘IR not event’ method, date of radiological or clinical progression after incomplete resection; landmark method, landmark time. According to these definitions, the theoretical strengths and weaknesses of the three definitions are investigated. Three patterns of progression-free survival and overall survival were estimated using the data of the Japan Clinical Oncology Group studies. Theoretically, ‘IR = event’ inflates alpha error while ‘IR not event’ method and landmark method reduce the statistical power under the alternative hypothesis. In JCOG9907, hazard ratios for the three definitions were: ‘IR = event’, 0.80 (95% confidence interval, 0.59–1.07; P = 0.13); ‘IR not event’, 0.81 (95% confidence interval, 0.60–1.09; P = 0.16); landmark, 0.80 (95% confidence interval, 0.59–1.07; P = 0.15). No P value of any methods corresponded with the positive result for overall survival (P = 0.03). In the preoperative arms of the four studies, maximum differences in median and percentage of 1 year progression-free survival among the three definitions were 0–6.4 months and 1.2–5.2%. Progression-free survival sometimes fails as a surrogate of overall survival, and differences among results obtained with various progression-free survival definitions can be large. Overall survival should be used as primary endpoint in studies evaluating preoperative therapy.
