Does T Stage Affect Prognosis in Patients With Stage Iv B Differentiated Thyroid Cancer

Objective: Differentiated thyroid cancer (DTC), the most common subtype of thyroid cancer, has a relatively good prognosis. The 8^th edition of the American Joint Committee on Cancer (AJCC) pathologic tumor-node-metastasis (T [primary tumor size], N [regional lymph nodes], M [distant metastasis]) staging system did not take the T stage into consideration in stage IV B DTC patients. We evaluated the prognostic value of the T stage for advanced DTC survival.Methods: DTC cases that were considered stage IV B in the AJCC 8^th edition were extracted from the Surveillance, Epidemiology, and End Results database. T stage (AJCC 6^th standard) was categorized into T0–2, T3 and T4. We analyzed overall survival (OS) and cancer specific survival (CSS) in the overall group as well as in pathologic subgroups. We used the Kaplan-Meier method and log-rank test for univariate analysis and the Cox regression model for multivariate analysis.Results: A total of 519 cases were extracted. Patients with earlier T stages showed significantly better OS and CSS in univariate analysis. T stage was an independent prognostic factor for both OS and CSS in multivariate analysis. Subgroup analysis in papillary and follicular thyroid cancer showed that T4 was an independent prognostic factor for both OS and CSS.Conclusion: AJCC 8 stage IV B DTC patients could be further stratified by T stage. Further studies with larger samples and AJCC 8 T stage information are necessary.Abbreviations: AJCC = American Joint Committee on Cancer; CI = confidence interval; CSS = cancer specific survival; DTC = differentiated thyroid cancer; FTC = follicular thyroid cancer; FVPTC = follicular variant of papillary thyroid carcinoma; HR = hazard ratio; OS = overall survival; PTC = papillary thyroid cancer; SEER = surveillance, epidemiology, and end results database     

不同体质量指数对腹腔镜结直肠癌切除术患者临床疗效和远期预后的影响

摘要 目的：研究不同体质量指数（BMI）对腹腔镜结直肠癌切除术患者临床疗效和远期预后的影响。方法：将从2014年1月～2016年1月于我院接受腹腔镜结直肠癌切除术治疗的110例患者纳入研究。将所有受试者根据BMI的差异分作正常组（18.6 kg/m²≦BMI<23.0 kg/m²）35例、超重组（23.0 kg/m²≦BMI<25.0 kg/m²）53例、肥胖组（BMI≧25.0 kg/m²）22例。分析三组患者各项基线资料,临床疗效,术后并发症发生情况,远期预后等方面的差异。结果：三组患者各项基线资料比较差异均不明显（均P＞0.05）。肥胖组手术时长为（268.01±36.14）min,均明显高于正常组、超重组的（211.73±30.56）min、（224.12±34.87）min（均P＜0.05）;三组术中失血量、肛门排气时间以及住院康复时间对比均不明显（均P＞0.05）。三组患者术后肺部感染、下肢静脉血栓、切口感染以及吻合口出血发生率对比均不明显（均P＞0.05）。正常组5年生存率为45.71%（16/35）,超重组5年生存率为47.17%（25/53）,肥胖组5年生存率为45.45%（10/22）,三组比较差异无统计学意义（均P＞0.05）。结论：不同BMI对腹腔镜结直肠癌切除术患者的手术时长具有一定影响,但和远期预后无关,值得临床重点关注。     

Cdkl在浆液性卵巢癌中的表达及其与化疗耐药及预后的相关性

目的：卵巢癌是女性生殖致死率最高的恶性肿瘤。Cdkl作为细胞周期依赖性激酶中的核心分子,对肿瘤细胞的发生发展具有重要作用。本文旨在探讨Cdkl蛋白在上皮性浆液性卵巢癌中的表达情况,并分析其表达水平与患者临床病理特征、化疗反应及预后之间的关系。方法：采用免疫组化法检测68例浆液性卵巢癌中Cdkl蛋白的表达情况,并结合临床资料分析Cdkl蛋白的表达水平在浆液性卵巢癌患者中的意义。结果：Cdkl在浆液性卵巢癌患者中具有不同程度的阳性表达,其表达水平和患者的年龄、病理分化程度、淋巴结转移情况及临床分期无明显相关性（P〉0．05）,但是其高表达与化疗耐药明显相关（P=0．040）。化疗耐药的卵巢癌患者中Cdkl的蛋白表达明显高于化疗敏感组,并且生存分析发现,高表达Cdkl的患者预后较差。结论：本研究证明Cdkl在浆液性卵巢癌中有较高表达,并且Cdkl的表达与卵巢癌化疗后复发有关,高的Cdkl表达预示着较差的预后。Cdkl可能是晚期浆液性卵巢癌治疗的新靶点。     

体质指数与直肠癌的关系探讨

目的：探讨体质指数（bodymassindex,BMI）与我国直肠癌发病的关系,为直肠癌的预防提供参考。方法：用病例．对照研究方法分析353例首次确诊的直肠癌患者和354名健康人的BMI,比较两组人群BMI的情况。结果：首次确诊的直肠癌患者平均BMI为（24．54±4．48）kg／m^2,健康对照人群平均BMI为（23．58±3．12）kg／m^2,直肠癌患者的BMI明显高于健康对照人群,其差别具有统计学意义（P〈0．001）。根据性别的不同进行分组后,可以看出不同性别直肠癌患者的BMI均比健康对照组高。logistic回归分析,BMI的升高是直肠癌发生的危险因素,OR值为1．056（95％CI,1．027±1．089）。结论：直肠癌的发生与BMI有关。     

Association between Body Mass Index and Prognosis of Colorectal Cancer: A Meta-Analysis of Prospective Cohort Studies

Studies have reported conflicting results on the association between body mass index (BMI) and prognosis of colorectal cancer. Therefore, we have conducted a meta-analysis of prospective studies, which examined the association of pre- and post-diagnostic BMI with colorectal cancer-specific mortality and all-cause mortality in patients with colorectal cancer. We searched Medline and EMBASE database published between 1970 and September 2014. A total of 508 articles were identified, of which 16 prospective cohort studies were included for the current meta-analysis. The analysis included 58,917 patients who were followed up over a period ranging from 4.9 to 20 years (median: 9.9 years). We found that being underweight before cancer diagnosis was associated with increased all-cause mortality (Relative risk [RR]: 1.63, 95% CI: 1.18–2.23, p < 0.01) and being obese (BMI ≥ 30 kg/m²) before cancer diagnosis was associated with increased colorectal cancer-specific mortality (RR: 1.22, 95% CI: 1.003–1.35, p < 0.01) and all-cause mortality (RR: 1.25, 95% CI: 1.14–1.36, p < 0.01). On the other hand, being underweight (RR: 1.33, 95% CI: 1.20–1.47, p < 0.01), obese (RR: 1.08, 95% CI: 1.03–1.3, p < 0.01), and class II/III obese (BMI ≥ 35 kg/m²; RR: 1.13, 95% CI: 1.04–1.23, p < 0.01) after diagnosis were associated with significantly increased all-cause mortality. Being obese prior to diagnosis of colorectal cancer was associated with increased colorectal cancer-specific mortality and all-cause mortality, whereas being obese after diagnosis was associated with increased all-cause mortality. The associations with being underweight may reflect reverse causation. Maintaining a healthy body weight should be discussed with colorectal cancer survivors.     

YAP Promotes Ovarian Cancer Cell Tumorigenesis and Is Indicative of a Poor Prognosis for Ovarian Cancer Patients

YAP is a key component of the Hippo signaling pathway and plays a critical role in the development and progression of multiple cancer types, including ovarian cancer. However, the effects of YAP on ovarian cancer development in vivo and its downstream effectors remain uncertain. In this study we found that strong YAP expression was associated with poor ovarian cancer patient survival. Specifically, we showed for the first time that high YAP expression levels were positively correlated with TEAD4 gene expression, and their co-expression was a prognostic marker for poor ovarian cancer survival. Hyperactivation of YAP by mutating its five inhibitory phosphorylation sites (YAP-5SA) increased ovarian cancer cell proliferation, resistance to chemotherapeutic drugs, cell migration, and anchorage-independent growth. In contrast, expression of a dominant negative YAP mutant reversed these phenotypes in ovarian cancer cells both in vitro and in vivo. Our results suggested that YAP caused these effects by promoting an epithelial-to-mesenchymal transition. Thus, YAP promotes ovarian cancer cell growth and tumorigenesis both in vitro and in vivo. Further, high YAP and TEAD4 expression is a prognostic marker for ovarian cancer progression and a potential target for ovarian cancer treatment.     

Survivin和COX-2的表达及与胰腺癌预后的关系

目的:评价Survivin和COX-2在胰腺癌中的表达与预后的关系.方法:采用免疫组化二步法检测63例手术切除的原发性胰腺癌组织及11例癌旁非肿瘤胰腺组织中Survivin和COX-2的表达情况.应用spearman相关分析Survivin与COX-2表达的相关性.用Kaplan-Meier法分析生存曲线,多变量Cox比例风险回归模型筛选影响患者生存的独立预后因素.结果:Survivin、COX-2蛋白在胰腺腺癌中的表达呈正相关(r=0.613,P=0.000).Survivin阻性表达患者中位生存时间(9个月)明显小于阴性表达者中位生存时间(21个月),P=0.000; COX-2阳性表达患者中位生存时间(10个月)也明显小于阴性表达者生存时间(大于36个月),P=0.000; Survivin阴性/COX-2阴性组患者(9例)中位生存时间(大于36个月)及1年累计生存率为88.9％,均明显高于单一阳性表达或均阳性表达组.多因素分析(Cox模型)显示分化程度(P=0.002)、临床分期(P=0.000)及Survivin过表达(P=0.005)为影响胰腺癌预后的独立因素.结论:Survivin、COX-2蛋白在胰腺癌组织中表达上调且呈正相关,二者在胰腺癌的发生发展中可能具有协同作用,有望作为靶点用于胰腺癌的靶向治疗.患者的分化程度、临床分期及Survivin的表达水平是胰腺癌患者手术后生存的独立危险因素.     

Cdk1在浆液性卵巢癌中的表达及其与化疗耐药及预后的相关性

目的:卵巢癌是女性生殖致死率最高的恶性肿瘤。Cdk1作为细胞周期依赖性激酶中的核心分子,对肿瘤细胞的发生发展具有重要作用。本文旨在探讨Cdk1蛋白在上皮性浆液性卵巢癌中的表达情况,并分析其表达水平与患者临床病理特征、化疗反应及预后之间的关系。方法:采用免疫组化法检测68例浆液性卵巢癌中Cdk1蛋白的表达情况,并结合临床资料分析Cdk1蛋白的表达水平在浆液性卵巢癌患者中的意义。结果:Cdk1在浆液性卵巢癌患者中具有不同程度的阳性表达,其表达水平和患者的年龄、病理分化程度、淋巴结转移情况及临床分期无明显相关性(P0.05),但是其高表达与化疗耐药明显相关(P=0.040)。化疗耐药的卵巢癌患者中Cdk1的蛋白表达明显高于化疗敏感组,并且生存分析发现,高表达Cdk1的患者预后较差。结论:本研究证明Cdk1在浆液性卵巢癌中有较高表达,并且Cdk1的表达与卵巢癌化疗后复发有关,高的Cdk1表达预示着较差的预后。Cdk1可能是晚期浆液性卵巢癌治疗的新靶点。     

Body Mass Index Genetic Risk Score and Endometrial Cancer Risk

Genome-wide association studies (GWAS) have identified common variants that predispose individuals to a higher body mass index (BMI), an independent risk factor for endometrial cancer. Composite genotype risk scores (GRS) based on the joint effect of published BMI risk loci were used to explore whether endometrial cancer shares a genetic background with obesity. Genotype and risk factor data were available on 3,376 endometrial cancer case and 3,867 control participants of European ancestry from the Epidemiology of Endometrial Cancer Consortium GWAS. A BMI GRS was calculated by summing the number of BMI risk alleles at 97 independent loci. For exploratory analyses, additional GRSs were based on subsets of risk loci within putative etiologic BMI pathways. The BMI GRS was statistically significantly associated with endometrial cancer risk (P = 0.002). For every 10 BMI risk alleles a woman had a 13% increased endometrial cancer risk (95% CI: 4%, 22%). However, after adjusting for BMI, the BMI GRS was no longer associated with risk (per 10 BMI risk alleles OR = 0.99, 95% CI: 0.91, 1.07; P = 0.78). Heterogeneity by BMI did not reach statistical significance (P = 0.06), and no effect modification was noted by age, GWAS Stage, study design or between studies (P≥0.58). In exploratory analyses, the GRS defined by variants at loci containing monogenic obesity syndrome genes was associated with reduced endometrial cancer risk independent of BMI (per BMI risk allele OR = 0.92, 95% CI: 0.88, 0.96; P = 2.1 x 10⁻⁵). Possessing a large number of BMI risk alleles does not increase endometrial cancer risk above that conferred by excess body weight among women of European descent. Thus, the GRS based on all current established BMI loci does not provide added value independent of BMI. Future studies are required to validate the unexpected observed relation between monogenic obesity syndrome genetic variants and endometrial cancer risk.     

Estrogen Receptors alpha and beta in Ovarian Cancer: Expression Level and Prognosis

The quantitative immunofluorescence assay of serous ovarian cancer tissue for the expression of estrogen receptors (ERα and ERβ) revealed a higher expression level of ERβ in comparison with ERα in all surgical tumor samples investigated. Significant differences in the expression level of the markers were detected “from tumor to tumor.” A high expression level of both ERα (≥ 25%) and ERβ (≥ 44%) in the tumor predicts a significantly longer progression-free survival time (p < 0.01) in the patients after the first line of platinum and taxane-based adjuvant chemotherapy.     

Stem Cell-Like Gene Expression in Ovarian Cancer Predicts Type II Subtype and Prognosis

Although ovarian cancer is often initially chemotherapy-sensitive, the vast majority of tumors eventually relapse and patients die of increasingly aggressive disease. Cancer stem cells are believed to have properties that allow them to survive therapy and may drive recurrent tumor growth. Cancer stem cells or cancer-initiating cells are a rare cell population and difficult to isolate experimentally. Genes that are expressed by stem cells may characterize a subset of less differentiated tumors and aid in prognostic classification of ovarian cancer. The purpose of this study was the genomic identification and characterization of a subtype of ovarian cancer that has stem cell-like gene expression. Using human and mouse gene signatures of embryonic, adult, or cancer stem cells, we performed an unsupervised bipartition class discovery on expression profiles from 145 serous ovarian tumors to identify a stem-like and more differentiated subgroup. Subtypes were reproducible and were further characterized in four independent, heterogeneous ovarian cancer datasets. We identified a stem-like subtype characterized by a 51-gene signature, which is significantly enriched in tumors with properties of Type II ovarian cancer; high grade, serous tumors, and poor survival. Conversely, the differentiated tumors share properties with Type I, including lower grade and mixed histological subtypes. The stem cell-like signature was prognostic within high-stage serous ovarian cancer, classifying a small subset of high-stage tumors with better prognosis, in the differentiated subtype. In multivariate models that adjusted for common clinical factors (including grade, stage, age), the subtype classification was still a significant predictor of relapse. The prognostic stem-like gene signature yields new insights into prognostic differences in ovarian cancer, provides a genomic context for defining Type I/II subtypes, and potential gene targets which following further validation may be valuable in the clinical management or treatment of ovarian cancer.     

Body Mass Index and Risk of Pancreatic Cancer in a Chinese Population

Few studies have examined the association between body mass index (BMI: kg/m²) and pancreatic cancer risk in Asian populations. We examined this relationship in 51,251 Chinese men and women aged 45–74 who enrolled between 1993 and 1998 in the population based, prospective Singapore Chinese Health Study. Data were collected through in-person interviews. By December 31, 2011, 194 cohort participants had developed pancreatic cancer. A Cox proportional hazards model was used to estimate hazard ratios (HR) and their 95% confidence intervals (95% CI). We hypothesized the association between BMI and pancreatic cancer risk may vary by smoking status (ever v. never) and there was evidence for this as the interaction between BMI and smoking status was significant (p = 0.018). Among ever smokers, being classified as underweight (BMI <18.5 kg/m²), was associated with a significantly elevated risk of pancreatic cancer relative to smokers with a BMI of 21.5–24.4 kg/m² (HR = 1.99, 95% CI  =  1.03–3.84). This association was strengthened after exclusion of the first three years of follow-up time. Among never smokers, there was no association between BMI and pancreatic cancer risk. However, after excluding pancreatic cancer cases and person-years in the first three years of follow-up, never smokers with a BMI ≥ 27.5 kg/m² showed a suggestive increased risk of pancreatic cancer relative to never smokers with a BMI of 21.5–24.4 kg/m² (HR  =  1.75, 95% CI  =  0.93–3.3). In conclusion, Singaporean Chinese who were underweight with a history of smoking had an increased risk of developing pancreatic cancer, whereas there was no significant association between BMI and pancreatic cancer in never smokers.     

Relationships Between the Body Mass Index and Body Composition

The aims of this study were to evaluate the Body Mass Index (BMI) (weight/stature²) as a proxy for percent body fat (%BF) and to determine its association with fat-free mass (FFM). Multivariate analysis of variance and partial correlations were used to examine relationships between BMI and %BF and FFM from densitometry for 504 men and 511 women, aged 20 to 45 years. Sensitivity/specificity analyses used cut offs of 28 kg/m² in men and 26 kg/m² in women for BMI, and 25% in men and 33% in women for %BF. Significantly higher associations existed in each gender between BMI and %BF in the upper BMI tertile than in the lower BMI tertiles. In the lower BMI tertiles, correlations between BMI and FFM were approximately twice as large as those between BMI and %BF. The BMI correctly identified about 44% of obese men, and 52% of obese women when obesity was determined from %BF. BMI is an uncertain diagnostic index of obesity. Results of Receiver Operator Characteristic (ROC) analyses using %BF and total body fat, both provided a BMI of 25 kg/m² in men and 23 kg/m² in women as diagnostic screening cut offs for obesity.     

The Relationship of Body Mass Index to Reproductive Factors in Pre- and Postmenopausal African-American Women With and Without Breast Cancer

To date, there are virtually no existing data on the relationship between obesity, menopausal status, and breast cancer in African-Americans. Therefore, the present study was designed to test the following hypotheses in an African-American population: (1) there exists a positive association between BMI and breast cancer among postmenopausal women; (2) there exists an inverse association between BMI and breast cancer among premenopausal women; and (3) similar associations between BMI and reproductive factors exist for both pre- and postmenopausal breast cancer cases. The study population comprised 357 African-American women (n=193 breast cancer cases; n=164 controls). No significant differences were observed between premenopausal cases and controls for BMI, obesity categories, and reproductive factors. Among the postmenopausal women, the cases had significantly lower weight and BMI levels than the controls. Age at first pregnancy and parity were significantly lower among postmenopausal cases than their controls. No significant associations were revealed between body mass index and breast cancer for pre- and postmenopausal women. In the present study, early age at menarche was the only reproductive factor that was an independent predictor of BMI for both pre- and postmenopausal women, irrespective of breast cancer status. Also, these findings strongly suggest the need to consider reproductive factors, particularly age at menarche, as a covariate of BMI and other obesity-related diseases.     

Body Mass Index and the Risk of Dementia among Louisiana Low Income Diabetic Patients

BackgroundThe association between obesity and dementia risk remains debatable and no studies have assessed this association among diabetic patients. The aim of our study was to investigate the association between body mass index (BMI) and dementia risk among middle and low income diabetic patients.Conclusions/SignificanceHigher baseline BMI was associated with a lower risk of dementia among diabetic patients, and this association was stronger among white than among African American diabetic patients.     

The Association between Body Mass Index and Mortality in Incident Dialysis Patients

Objectives

To study the body mass index (BMI) trajectory in patients with incident end-stage kidney disease and its association with all-cause mortality.

Methods

This longitudinal cohort study included 17022 adult patients commencing hemodialysis [HD] (n = 10860) or peritoneal dialysis [PD] (n = 6162) between 2001 and 2008 and had ≥6-month follow-up and ≥2 weight measurements, using the Australia and New Zealand Dialysis and Transplant Registry data. The association of time-varying BMI with all-cause mortality was explored using multivariate Cox regression models.

Results

The median follow-up was 2.3 years. There was a non-linear change in the mean BMI (kg/m²) over time, with an initial decrease from 27.6 (95% confidence interval [CI]: 27.5, 27.7) to 26.7 (95% CI: 26.6, 26.9) at 3-month, followed by increments to 27.1 (95% CI: 27, 27.2) at 1-year and 27.2 (95% CI: 26.8, 27.1) at 3-year, and a gradual decrease subsequently. The BMI trajectory was significantly lower in HD patients who died than those who survived, although this pattern was not observed in PD patients. Compared to the reference time-varying BMI category of 25.1–28 kg/m², the mortality risks of both HD and PD patients were greater in all categories of time-varying BMI <25 kg/m². The mortality risks were significantly lower in all categories of time-varying BMI >28.1 kg/m² among HD patients, but only in the category 28.1–31 kg/m² among PD patients.

Conclusions

BMI changed over time in a non-linear fashion in incident dialysis patients. Time-varying measures of BMI were significantly associated with mortality risk in both HD and PD patients.     

Let-7 Prevents Early Cancer Progression by Suppressing Expression of the Embryonic Gene HMGA2

The microRNA let-7 regulates late embryonic development by suppressing expression of a number of genes such as c-myc and RAS as well as the embryonic gene high mobility group, A2 (HMGA2). We now demonstrate that HMGA2 is more efficiently targeted by let-7 than RAS. Its expression inversely correlates with the expression of let-7 in the NCI60 cells lines, and the expression of RAS does not change when amounts of let-7 that efficiently silence expression of HMGA2 are introduced into tumor cells. We did not find a difference in the expression of HMGA2 between primary ovarian cancer samples and matching metastases, suggesting that the expression of HMGA2 represents an early event during cancer progression. The late repression of HMGA2 by let-7 during embryonic development, and the early reexpression of HMGA2 during cancer development, is in line with the hypothesis that cancer development represents a case of reverse embryogenesis.     

Expression of Sirtuin 1 and 2 Is Associated with Poor Prognosis in Non-Small Cell Lung Cancer Patients

Background

Sirtuin 1 (SIRT1) and sirtuin 2 (SIRT2) are NAD+-dependent protein deacetylases involved in the regulation of key cancer-associated genes. In this study we evaluated the relevance of these deacetylases in lung cancer biology.

Material and Methods

Protein levels of SIRT1 and SIRT2 were determined in non-small cell lung cancer (NSCLC) cell lines and primary tumors from 105 patients. Changes in proliferation were assessed after SIRT1 and SIRT2 downregulation in lung cancer cell lines using siRNA-mediated technology or tenovin-1, a SIRT1 and SIRT2 inhibitor.

Results

High SIRT1 and SIRT2 protein levels were found in NSCLC cell lines compared with non-tumor lung epithelial cells. The expression of SIRT1 and SIRT2 proteins was also significantly higher in lung primary tumors than in normal tissue (P<0.001 for both sirtuins). Stronger nuclear SIRT1 staining was observed in adenocarcinomas than in squamous cell carcinomas (P=0.033). Interestingly, in NSCLC patients, high SIRT1 and SIRT2 expression levels were associated with shorter recurrence-free survival (P=0.04 and P=0.007, respectively). Moreover, the combination of high SIRT1 and SIRT2 expression was an independent prognostic factor for shorter recurrence-free survival (P=0.002) and overall survival (P=0.022). In vitro studies showed that SIRT1 and/or SIRT2 downregulation significantly decreased proliferation of NSCLC.

Conclusions

Our results support the hypothesis that SIRT1 and SIRT2 have a protumorigenic role in lung cancer, promoting cell proliferation. Moreover, the expression of these proteins is associated with poor prognosis in NSCLC patients and may help to identify those NSCLC patients with high risk of recurrence that could benefit from adjuvant therapy after resection.