前列腺癌根治标本的大体检查和处理一直是病理医师的一个巨大挑战。由于离体后的前列腺癌的肿块与前列腺增生症的背景在外观形状上相差不明显，肿瘤常为多灶性，且大部分根治性切除的前列腺标本曾行1～2个疗程的内分泌治疗，肿瘤组织有...前列腺癌根治标本的大体检查和处理一直是病理医师的一个巨大挑战。由于离体后的前列腺癌的肿块与前列腺增生症的背景在外观形状上相差不明显，肿瘤常为多灶性，且大部分根治性切除的前列腺标本曾行1～2个疗程的内分泌治疗，肿瘤组织有一定程度退变，大体上很难辨认。此外为判断外科手术边缘是否切除干净和防止遗漏，病理医师通常将整个前列腺标本全部取材，但因受传统的包埋盒大小及厚度的限制，前列腺常被切割成40～80块左右的组织，这样不仅破坏了前列腺的完整性，更给后续的制片和阅片带来十分繁琐的工作。作者参考国外的经验［1-3］，尝试前列腺癌根治标本的大切片（4 cm ×3 cm或7 cm ×5 cm）制作，对前列腺整个切面进行分层取材，并对后续的组织固定、脱水、切片和染色等各个工作环节不断摸索和改进，成功地完成了352例前列腺癌大切片，为病理医师更准确和全面地观察前列腺癌病灶及综合性评价提供了极大的便利，也为临床治疗提供了很大的帮助。展开更多
AIM： Prostaglandin G/H synthase 2 （PTGS2 or COX2） is one of the key factors in the cellular response to inflammation. PTGS2 is expressed in the affected intestinal segments of patients with inflammatory bowel disea...AIM： Prostaglandin G/H synthase 2 （PTGS2 or COX2） is one of the key factors in the cellular response to inflammation. PTGS2 is expressed in the affected intestinal segments of patients with inflammatory bowel diseases （IBD）. In IBD patients, non-steroidal anti-inflammatory drugs, which have been shown to reduce both the production and activity of PTGS2, may activate IBD and aggravate the symptoms. We aimed at examining genetic variants of PTGS2 that may be risk factors for IBD. METHODS： We genotyped 291 individuals diagnosed with IBD and 367 controls from the Dutch population for the five most frequent polymorphisms of the PTG52 gene. Clinical data were collected on all patients. DNA was extracted via normal laboratory methods. Genotyping was carried out using multiplex PCR followed by the Invader Assay and the 5＇ exonuclease assay （TaqMan）. New polymorphism screening was performed by pre-screening with denaturing high-performance liquid chromatography, followed by fluorescent sequencing. RESULTS： Allele 5209G was weakly associated with Crohn＇s disease （odds ratio [OR] 1.63, 95% confidence interval [CI] 1.03-2.57）, and allele 8473T with ulcerativecolitis （OR 1.50, 95%CI 1.00-2.27）. The haplotype including both alleles showed a strong association with IBD （OR 13.15, 95%CI 3.17-116.15）. This haplotype, while rare （-0.3%） in the general population, is found more frequently in patients （3.5%）. CONCLUSION： Our data suggest that this haplotype of PTGS2 contributes to the susceptibility of IBD.展开更多
The generalized linear model is an indispensable tool for analyzing non-Gaussian response data, with both canonical and non-canonical link functions comprehensively used. When missing values are present, many existing...The generalized linear model is an indispensable tool for analyzing non-Gaussian response data, with both canonical and non-canonical link functions comprehensively used. When missing values are present, many existing methods in the literature heavily depend on an unverifiable assumption of the missing data mechanism, and they fail when the assumption is violated. This paper proposes a missing data mechanism that is as generally applicable as possible, which includes both ignorable and nonignorable missing data cases, as well as both scenarios of missing values in response and covariate.Under this general missing data mechanism, the authors adopt an approximate conditional likelihood method to estimate unknown parameters. The authors rigorously establish the regularity conditions under which the unknown parameters are identifiable under the approximate conditional likelihood approach. For parameters that are identifiable, the authors prove the asymptotic normality of the estimators obtained by maximizing the approximate conditional likelihood. Some simulation studies are conducted to evaluate finite sample performance of the proposed estimators as well as estimators from some existing methods. Finally, the authors present a biomarker analysis in prostate cancer study to illustrate the proposed method.展开更多
文摘前列腺癌根治标本的大体检查和处理一直是病理医师的一个巨大挑战。由于离体后的前列腺癌的肿块与前列腺增生症的背景在外观形状上相差不明显，肿瘤常为多灶性，且大部分根治性切除的前列腺标本曾行1～2个疗程的内分泌治疗，肿瘤组织有一定程度退变，大体上很难辨认。此外为判断外科手术边缘是否切除干净和防止遗漏，病理医师通常将整个前列腺标本全部取材，但因受传统的包埋盒大小及厚度的限制，前列腺常被切割成40～80块左右的组织，这样不仅破坏了前列腺的完整性，更给后续的制片和阅片带来十分繁琐的工作。作者参考国外的经验［1-3］，尝试前列腺癌根治标本的大切片（4 cm ×3 cm或7 cm ×5 cm）制作，对前列腺整个切面进行分层取材，并对后续的组织固定、脱水、切片和染色等各个工作环节不断摸索和改进，成功地完成了352例前列腺癌大切片，为病理医师更准确和全面地观察前列腺癌病灶及综合性评价提供了极大的便利，也为临床治疗提供了很大的帮助。
基金Supported by The Grants from the International Agency for Research on Cancer (Special Training Award to DGC)the French Association for Research on Cancer (grant #7478)the Crohn's and Colitis Foundation of America (to ASP)
文摘AIM： Prostaglandin G/H synthase 2 （PTGS2 or COX2） is one of the key factors in the cellular response to inflammation. PTGS2 is expressed in the affected intestinal segments of patients with inflammatory bowel diseases （IBD）. In IBD patients, non-steroidal anti-inflammatory drugs, which have been shown to reduce both the production and activity of PTGS2, may activate IBD and aggravate the symptoms. We aimed at examining genetic variants of PTGS2 that may be risk factors for IBD. METHODS： We genotyped 291 individuals diagnosed with IBD and 367 controls from the Dutch population for the five most frequent polymorphisms of the PTG52 gene. Clinical data were collected on all patients. DNA was extracted via normal laboratory methods. Genotyping was carried out using multiplex PCR followed by the Invader Assay and the 5＇ exonuclease assay （TaqMan）. New polymorphism screening was performed by pre-screening with denaturing high-performance liquid chromatography, followed by fluorescent sequencing. RESULTS： Allele 5209G was weakly associated with Crohn＇s disease （odds ratio [OR] 1.63, 95% confidence interval [CI] 1.03-2.57）, and allele 8473T with ulcerativecolitis （OR 1.50, 95%CI 1.00-2.27）. The haplotype including both alleles showed a strong association with IBD （OR 13.15, 95%CI 3.17-116.15）. This haplotype, while rare （-0.3%） in the general population, is found more frequently in patients （3.5%）. CONCLUSION： Our data suggest that this haplotype of PTGS2 contributes to the susceptibility of IBD.
基金supported by the Chinese 111 Project B14019the US National Science Foundation under Grant Nos.DMS-1305474 and DMS-1612873the US National Institutes of Health Award UL1TR001412
文摘The generalized linear model is an indispensable tool for analyzing non-Gaussian response data, with both canonical and non-canonical link functions comprehensively used. When missing values are present, many existing methods in the literature heavily depend on an unverifiable assumption of the missing data mechanism, and they fail when the assumption is violated. This paper proposes a missing data mechanism that is as generally applicable as possible, which includes both ignorable and nonignorable missing data cases, as well as both scenarios of missing values in response and covariate.Under this general missing data mechanism, the authors adopt an approximate conditional likelihood method to estimate unknown parameters. The authors rigorously establish the regularity conditions under which the unknown parameters are identifiable under the approximate conditional likelihood approach. For parameters that are identifiable, the authors prove the asymptotic normality of the estimators obtained by maximizing the approximate conditional likelihood. Some simulation studies are conducted to evaluate finite sample performance of the proposed estimators as well as estimators from some existing methods. Finally, the authors present a biomarker analysis in prostate cancer study to illustrate the proposed method.
