Patterns of Medical Care Cost by Service Type for Patients With Recurrent and De Novo Advanced Cancer

ObjectivesThere is limited knowledge about the cost patterns of patients who receive a diagnosis of de novo and recurrent advanced cancers in the United States.MethodsData on patients who received a diagnosis of de novo stage IV or recurrent breast, colorectal, or lung cancer between 2000 and 2012 from 3 integrated health systems were used to estimate average annual costs for total, ambulatory, inpatient, medication, and other services during (1) 12 months preceding de novo or recurrent diagnosis (preindex) and (2) diagnosis month through 11 months after (postindex), from the payer perspective. Generalized linear regression models estimated costs adjusting for patient and clinical factors.ResultsPatients who developed a recurrence <1 year after their initial cancer diagnosis had significantly higher total costs in the preindex period than those with recurrence ≥1 year after initial diagnosis and those with de novo stage IV disease across all cancers (all P < .05). Patients with de novo stage IV breast and colorectal cancer had significantly higher total costs in the postindex period than patients with cancer recurrent in <1 year and ≥1 year (all P < .05), respectively. Patients in de novo stage IV and those with recurrence in ≥1 year experienced significantly higher postindex costs than the preindex period (all P < .001).ConclusionsOur findings reveal distinct cost patterns between patients with de novo stage IV, recurrent <1-year, and recurrent ≥1-year cancer, suggesting unique care trajectories that may influence resource use and planning. Future cost studies among patients with advanced cancer should account for de novo versus recurrent diagnoses and timing of recurrence to obtain estimates that accurately reflect these care pattern complexities.     

地鳖纤溶蛋白口服时间/pH依赖结肠靶向微囊的开发及评价＊

地鳖中的纤溶活性蛋白是从地鳖中提取的具有抗栓及抗肿瘤作用的有效成分，其口服易被上消化道酶分解从而限制了应用。采用恒流泵滴制法开发地鳖纤溶活性蛋白时间/pH依赖口服结肠靶向微囊（EnpolypHaga fibrinolytic protein oral colon targeting microcapsules， CTM-EFP）。采用单因素实验和正交实验相结合的方法寻找到包封率为60.17 % ± 2.72 %、载药量为15.50 % ± 0.44 % 的最佳配方。扫描电子显微镜（SEM）显示微囊呈球形、表面光滑，在人工肠液中24 h的累积释放度为99.53 % ± 0.69 %，在人工胃液中24 h累积释放度为7.43 ± 1.04 %，通过时间/pH依赖达到结肠靶向作用。CTM-EFP在人工肠液中的体外释放曲线符合Korsmeyer方程，提示地鳖纤溶活性蛋白（EnpolypHaga fibrinolytic protein， EFP）是通过扩散和侵蚀机制结合释放的。CTM-EFP为EFP的口服给药提供了一种新的剂型，为EFP应用于临床提供参考。     

Current guidelines in the surgical management of hereditary colorectal cancers

Incidence of colorectal cancer (CRC) is on rise. While approximately 70% of all CRC cases are sporadic in nature, 20%-25% have familial aggregation and only < 5% is hereditary in origin. Identification of individuals with hereditary predilection for CRC is critical, as it has an impact on their overall surgical management including surgical timing, approach & technique and determines the role of prophylactic surgery and outcome. This review highlights the concept of hereditary CRC, provides insight into its molecular basis, possibility of its application into clinical practice and emphasizes the current treatment strategies with surgical management, based on the available international guidelines.     

利用酵母双杂交系统筛选NKD1结合蛋白质北大核心

目的:酵母双杂交技术筛选结肠癌细胞中与裸角质层同源蛋白1(naked cuticle homolog 1,NKD1)相互结合的蛋白质,从而进一步了解NKD1。方法:以结肠癌细胞SW480的cDNA为模板,克隆NKD1基因,并将其成功构建在pGBKT7诱饵载体上。利用酵母双杂交技术从结肠癌SW480细胞文库进行筛选。结果:初步筛选获得13个阳性克隆菌株。经测序,在数据库中BLAST比对后,共确定为8种不同基因编码的蛋白片段。回转实验进一步验证了这8种不同基因编码的蛋白均能够激活酵母双杂交系统中的His3、Ade2和LacZ报告基因。这8种不同基因中的4种基因编码的蛋白片段为YWHA蛋白家族成员,其中2种都是编码YWHAE蛋白片段。在结肠癌HCT116细胞中通过免疫共沉淀实验进一步验证,NKD1与YWHAE在结肠癌细胞中可以相互结合。结论:结肠癌细胞中,证实YWHAE是NKD1结合蛋白质,通过调控胰岛素的敏感性,进而调控结肠癌细胞对葡萄糖的摄入。     

Colon Cancer Tumor Location Defined by Gene Expression May Disagree With Anatomic Tumor Location

BackgroundCancers of the right colon have been shown to differ from left-side colon cancers in prognosis, response to epithelial growth factor receptor inhibitors, microsatellite instability and BRAF mutation status, and other molecular characteristics. Clinical application of these differences will benefit from a deeper understanding of how tumor location defines and is defined by gene expression.Materials and MethodsThis study was carried out using Affymetrix microarray datasets (Cohort A: training set, n = 352; validation set, n = 519) and samples from The Cancer Genome Atlas Colon Adenocarcinoma database (Cohort B: n = 408), in which tumor location was reported. Gene expression patterns characteristic of tumor side were identified in a manner unbiased by statistical classification method.ResultsIn the Cohort A validation set, the anatomic locations of 75% of tumors agree with the locations predicted by gene expression (so-called genomic location), whereas 8% of tumors had genomic locations discordant with their anatomic locations, and 17% of tumors had ambiguous genomic locations. Genomic location was a better predictor of microsatellite instability, CpG island methylator phenotype status, and BRAF mutation status than anatomic location. Tumors with ambiguous genomic location were significantly (P = 1.3 × 10⁻⁷) more likely to have the mesenchymal consensus molecular subtype (40%) than those with a specific genomic location (18%). A genomic signature to predict genomic location was defined.ConclusionTumor location is increasingly considered in deciding treatment of a colon tumor. We showed that genomic location was superior to anatomic location as a predictor of molecular characteristics, suggesting that it may be a more accurate predictor of response.     

左、右半结肠癌肝转移患者射频消融治疗疗效及生存的对比分析

目的:探讨原发部位分别位于左、右半结肠的结肠癌肝转移患者行超声引导下肝转移瘤射频消融术后的生存差异及预后影响因素分析。方法:回顾性分析2010年1月至2015年12月于我科行射频消融治疗的结肠癌肝转移患者100例，其中左半结肠癌62例，右半结肠癌38例，分析原发部位不同的结肠癌肝转移患者在进行超声引导下射频消融治疗后的生存情况。结果:左半结肠癌肝转移患者射频消融术后1、3、5年总体生存率及中位生存期均高于右半结肠癌肝转移患者（88.71% vs 73.68%、62.90% vs 30.02%、49.72% vs 26.33%、55个月 vs 23个月），且二者生存曲线差异具有统计学意义（P＜0.05）。经Log-rank检验及COX多因素分析，左、右半结肠癌肝转移患者射频消融治疗术后的生存情况存在差异。此外，原发灶淋巴结转移情况、患者术前CA199水平及原发灶分化程度是患者射频消融治疗术后生存情况的影响因素。结论:左半结肠癌肝转移患者射频消融术后整体生存率明显高于右半结肠癌肝转移患者，左半结肠癌与右半结肠癌肝转移患者在射频消融治疗术后生存状况存在明显差异。     

多学科会诊模式在结肠癌手术患者中的应用效果

目的分析多学科会诊(MDT)模式对结肠癌患者术后胃肠功能恢复及并发症的效果评价。方法将2017年1月至12月收治的50例结肠癌患者作为对照组,给予常规干预措施;将2018年1月至12月收治的50例结肠癌患者为观察组,采取MDT模式干预。比较两组患者的胃肠功能恢复情况及一般围手术期指标;干预前和干预后2周,采用世界卫生组织生存质量评估量表(WHOQOL-BREF)评估两组患者的生活质量;术后3天,采用视觉模拟评分法(VAS)评估两组患者腹胀发生情况;比较两组患者术后并发症发生情况。结果观察组患者肛门排气时间、首次排便时间、肠鸣音恢复时间、禁食时间、伤口愈合时间、住院时间、术后下床时间均短于对照组患者,差异均有统计学意义(P﹤0.05)。干预后2周,两组患者环境领域、社会领域、心理领域、生理领域及总体健康评分均高于本组干预前,且观察组患者环境领域、社会领域、心理领域、生理领域及总体健康评分均明显高于对照组患者,差异均有统计学意义(P﹤0.05)。术后3天,观察组患者的腹胀程度低于对照组患者,差异有统计学意义(P﹤0.05)。观察组患者术后并发症总发生率为6.0%,低于对照组患者的20.0%,差异有统计学意义(P﹤0.05)。结论MDT模式干预可促进患者术后胃肠功能恢复情况,缩短伤口愈合时间及住院时间,降低术后并发症发生率,并改善了患者的生活质量。     

miR-21的功能分析及其在结肠癌中的临床意义

目的:分析miR-21的功能及其在结肠癌中的临床意义。方法:采用miRWalk在线工具预测和筛选miR-21的靶基因，并使用DAVID分析靶基因的功能和信号通路；检测结肠癌患者和健康对照人群血清以及癌组织和癌旁组织标本的miR-21的表达水平；使用TCGA数据库中结肠癌的数据，分析miR-21表达水平与临床病理参数的关系以及与患者预后的关系。结果:共筛选出429个miR-21的靶基因，靶基因功能分析提示这些基因主要参与了正性调节代谢过程、蛋白结合等。结肠癌患者血清miR-21表达水平显著高于健康对照人群，差异有统计学意义（P<0.05）。TCGA数据显示，结肠癌组织中的miR-21表达水平与肿瘤的临床分期、肿瘤侵袭程度、淋巴结转移分期、远处转移分期无显著差异（P>0.05）。生存分析显示组织中高表达miR-21的患者其生存时间较低表达者短（P<0.05）。结论:miR-21调控多个肿瘤发生相关的基因，在结肠癌发生过程中具有重要的调控作用。结肠癌患者miR-21表达水平显著高于健康人群，且miR-21高表达的患者预后差。