Qidong: a crucible for studies on liver cancer etiology and prevention

Qidong(Jiangsu, China) has been of interest to cancer epidemiologists and biologists because, until recently, it was an endemic area for liver cancer, having amongst the highest incidence rates in the world. The establishment of the Qidong Cancer Registry together with the Qidong Liver Cancer Institute in 1972 has charted the patterns of liver cancer incidence and mortality in a stable population throughout a period of enormous economic, social, and environmental changes as well as of improvements in health care delivery. Updated incidence trends in Qidong are described. Notably, the China age-standardized incidence rate for liver cancer has dropped by over 50% in the past several decades. Molecular epidemiologic and genomic deep sequencing studies have affirmed that infection with hepatitis B virus as well as dietary exposure to aflatoxins through contamination of dietary staples such as corn, and to microcystins–blue-green algal toxins found in ditch and pond water – were likely important etiologic factors that account for the high incidence of liver cancer in this region. Public health initiatives to facilitate universal vaccination of newborns against HBV and to improve drinking water sources in this rural area, as well as economic and social mandates serendipitously facilitating dietary diversity, have led to precipitous declines in exposures to these etiologic factors, concomitantly driving substantive declines in the liver cancer incidence seen now in Qidong. In this regard, Qidong serves as a template for the global impact that a package of intervention strategies may exert on cancer burden.

Non-steroidal anti-inflammatory drugs and statins in relation to colorectal cancer risk

AIM： To investigate the association between individual or combined use of non-steroidal anti-inflammatory drugs （NSAIDs） or statins and colorectal cancer risk.METHODS： In a population-based case-control study in women, we examined the association between NSAIDs and statin use and the risk of colorectal cancers. We further investigated whether the use of statins modifies the protective effect of NSAIDs. Female cases （n = 669）of colorectal cancer aged 50-74 years were identified from a storewide registry in Wisconsin during 1999-2001. Community control women （n = 1375） were randomly selected from lists of licensed drivers and Medicare beneficiaries. Medication use and risk factor information were gathered during a structured telephone interview. A multivariable logistic regression model was used to calculate odds ratio （OR） and 95% confidence interval （CI）.RESULTS： Overall, NSAIDs users had a 30% reduction in risk of colorectal cancer （95% CI： 0.56-0.88）. Statin use was not associated with colorectal cancer risk （OR = 1.17, 95% CI： 0.74-1.85）, regardless of structural type （lipophilic or hydrophilic）, duration of use, or recency. There was no evidence of an interaction between NSAIDs and statins and colorectal cancer risk （P-interaction = 0.28）.CONCLUSION： Although our results confirm the inverse association between NSAIDs use and colorectal cancer risk, they do not support a risk reduction in statin users, or an interaction effect of combined NSAIDs and statin use.

Glucocorticoids and prostate cancer treatment： friend or foe？

Glucocorticoids have been used in the treatment of prostate cancer to slow disease progression, improve pain control and offset side effects of chemo- and hormonal therapy. However, they may also have the potential to drive prostate cancer growth via mutated androgen receptors or glucocorticoid receptors （GRs）. In this review we examine historical and contemporary use of glucocorticoids in the treatment of prostate cancer, review potential mechanisms by which they may inhibit or drive prostate cancer growth, and describe potential means of defining their contribution to the biology of prostate cancer.

Evaluation of the colorectal cancer risk conferred by rare UNC5C alleles

AIM: To evaluate the risk associated with variants of the UNC5C gene recently suspected to predispose to familial colorectal cancer (CRC).

Survival after inflammatory bowel disease-associated colorectal cancer in the Colon Cancer Family Registry

AIM: To investigate the survival of individuals with colorectal cancer (CRC) with inflammatory bowel disease (IBD-associated CRC) compared to that of individuals without IBD diagnosed with CRC. METHODS: Epidemiologic, clinical, and follow-up data were obtained from the Colon Cancer Family Registry (Colon CFR). IBD-associated cases were identified from self-report of physician diagnosis. For a subset of participants, medical records were examined to confirm self-report of IBD. Cox proportional hazards regression was applied to estimate adjusted hazard ratios (aHR) and 95%CI of mortality, comparing IBD-associated to non-IBD-associated CRC, adjusted for age at CRC diagnosis, sex, Colon CFR phase, and number of prior endoscopies. Following imputation to complete CRC stage information, adjustment for CRC stage was examined. RESULTS: A total of 7202 CRC cases, including 250 cases of IBD-associated CRC, were analyzed. Over a twelve year follow-up period following CRC diagnosis, 2013 and 74 deaths occurred among non-IBD associated CRC and IBD-associated CRC patients, respectively. The difference in survival between IBD-associated and non-IBD CRC cases was not statistically significant (aHR = 1.08; 95%CI: 0.85-1.36). However, the assumption of proportional hazards necessary for valid inference from Cox regression was not met over the entire follow-up period, and we therefore limited analyses to within five years after CRC diagnosis when the assumption of proportional hazards was met. Over this period, there was evidence of worse prognosis for IBD-associated CRC (aHR = 1.36; 95%CI: 1.05-1.76). Results were similar when adjusted for CRC stage, or restricted to IBD confirmed in medical records. CONCLUSION: These results support the hypothesis that IBD-associated CRC has a worse prognosis than non-IBD-associated CRC.

Application of Proteomics to Cancer Molecular Diagnostics

Strategies to achieve personalized medicine and improve public health encompass assessment of an individual's risk for disease,

Mismatch repair enzyme expression in primary and castrate resistant prostate cancer

Objective:Although the utility of immunohistochemistry(IHC)for assessing mismatch repair(MMR)protein expression has been demonstrated in solid tumors including primary prostate cancer(PCa),its utility has not been assessed in castration-resistant PCa(CRPC).Methods:Tissue microarrays were constructed from 127 radical prostatectomies and 155 CRPC metastases from 50 patients.MMR(MLH1,MSH2,MSH6,and PMS2)expression was assessed by IHC and gene expression arrays.Associations between MMR protein expression in PCa and CRPC and biochemical recurrence(BCR)or time from diagnosis to death respectively were determined.Results:There was no correlation between levels of MMR protein and BCR.Absence of MSH2 and MSH6 was the most pronounced at 15%and 22%in PCa and 17.8%and 16%in CRPC patients,respectively.MSH2 and MSH6 protein were absent in 9.4%and 8%of PCa and CRPC respectively.Absence of individual MMR proteins did not correlate with BCR or time from diagnosis to death.However absent MSH2/MSH6 in CRPC was associated with shorter time to death(pZ0.0006).Loss of MSH2 was verified at the gene expression level.This finding correlated with microsatellite instability previously reported in this CRPC cohort.

Blood and urine biomarkers in prostate cancer:Are we ready for reflex testing in men with an elevated prostate-specific antigen?

Objective:There is no consensus on the role of biomarkers in determining the utility of prostate biopsy in men with elevated prostate-specific antigen(PSA).There are numerous biomarkers such as prostate health index,4Kscore,prostate cancer antigen 3,ExoDX,SelectMDx,and Mi-Prostate Score that may be useful in this decision-making process.However,it is unclear whether any of these tests are accurate and cost-effective enough to warrant being a widespread reflex test following an elevated PSA.Our goal was to report on the clinical utility of these blood and urine biomarkers in prostate cancer screening.Methods:We performed a systematic review of studies published between January 2000 and October 2020 to report the available parameters and cost-effectiveness of the aforementioned diagnostic tests.We focus on the negative predictive value,the area under the curve,and the decision curve analysis in comparing reflexive tests due to their relevance in evaluating diagnostic screening tests.Results:Overall,the biomarkers are roughly equivalent in predictive accuracy.Each test has additional clinical utility to the current diagnostic standard of care,but the added benefit is not substantial to justify using the test reflexively after an elevated PSA.Conclusions:Our findings suggest these biomarkers should not be used in binary fashion and should be understood in the context of pre-existing risk predictors,patient’s ethnicity,cost of the test,patient life-expectancy,and patient goals.There are more recent diagnostic tools such as multi-parametric magnetic resonance imaging,polygenic single-nucleotide panels,IsoPSA,and miR Sentinel tests that are promising in the realm of prostate cancer screening and need to be investigated further to be considered a consensus reflexive test in the setting of prostate cancer screening.

Taking Care of Her: A Pilot Feasibility Study of a Caregiver Intervention for Women with Advanced Stage Ovarian Cancer

The purpose of this study is to examine the feasibility and short-term impact of a fully manualized, telephone-delivered intervention for spouse caregivers, Taking Care of Her (TCH). A total of 12 study participants from the Pacific NW were enrolled whose wife was diagnosed with Stage III ovarian cancer within 8 months. Feasibility was confirmed by rates of recruitment and retention;the quality of delivery of the intervention by telephone;and through data obtained on program acceptability during follow up exit interviews. Outcomes from the within-group analysis revealed improvements on standardized measures of spouses’ and patients’ depressed mood and anxiety;marital communication about the cancer;caregivers’ skills and confidence to manage the emotional toll of the illness on themselves and wives;and wives’ positive appraisal of spousal support. Study results suggest that the TCH Program has the potential to positively affect both spouse caregiver and patients’ adjustment to recently diagnosed advanced ovarian cancer. Telephone delivery holds promise for sustainability. A future clinical trial with a larger study sample is warranted.

Updates in endocrine therapy for metastatic breast cancer

Endocrine therapy(ET)remains the mainstay of treatment for steroid hormone receptor-positive,human epidermal growth factor 2(HER2)-negative metastatic breast cancer(MBC).Tumor resistance to hormone therapy has led to the development of novel endocrine drug combinations,transforming the landscape of MBC management.The options for ET are expanding,with promising agents in the pipeline.Although MBC remains incurable,many patients can enjoy years of survival with good quality of life by cycling through the many available agents.With the plethora of available agents and rapid approvals,clinicians look to evidencebased guidelines to assist in treatment selection to maximize patient well-being.In this review,we provide a contemporary review of the advances in ET and a suggested algorithm to guide clinicians in daily management of patients with hormone receptor-positive,HER2-negative MBC.We will discuss landmark trials and highlight their impact in reshaping treatment approaches.Finally,we will provide a glimpse into advances on the horizon and the promise they bring to improve outcomes in patients with advanced breast cancer.

Assessing Colorectal Cancer Screening Behaviors and Knowledge among At-Risk Hispanics in Southern New Mexico

Purpose: Colorectal cancer (CRC) mortality rates in New Mexico (NM) continue to be higher than national rates. Hispanic CRC mortality rates in NM surpass those of overall Hispanics in the US. This study was designed to characterize and understand factors contributing to low CRC screening rates in this border region. Methods: A CRC Knowledge Assessment Survey (KAS) was administered in either English or Spanish to 247 individuals attending community events throughout southern NM. A subset of these individuals completed an online CRC risk assessment survey managed by the National Cancer Institute (NCI). Data analysis tested for significant differences in knowledge, physician-patient CRC interactions, CRC risk level perception, and screening rates across diverse ethnic and age groups. Results: Both CRC knowledge and physician-patient CRC interactions were positively associated with participant screening history. Significant age and ethnic differences for CRC knowledge, physician-patient CRC interactions, and screening history in the NM border sample were also seen. Age-eligible Hispanics (50+) as well as those less than 50 years of age had lower CRC knowledge and were less likely to engage in physician-patient CRC interactions than non-Hispanic Whites (NHWs). The age-eligible Hispanics also reported lower CRC screening rates than their NHW counterparts. Conclusions: Low CRC knowledge and limited physician-patient CRC interactions appear to contribute to low screening rates in this NM population. Expanding education and outreach efforts for this border population are essential to promote early CRC detection and thereby decrease overall CRC mortality rates.

Development of an instrument to identify symptoms potentially indicative of ovarian cancer in a primary care clinic setting

Background: Several recently published studies suggest that screening for symptoms could improve the early diagnosis of ovarian cancer. This report describes the development of a simple and reliable method of collecting symptom information in a primary care clinic. Methods: 1200 women, ages 40 - 87, completed several versions of a draft symptom index (SI) assessment form during their visits to a primary care clinic. Factors associated with a positive SI result were examined. Providers were surveyed about acceptability of the symptom screening procedures. Findings: Variation in the instructions provided to women influenced the rate at which women indicated having symptoms indicative of a positive SI, 5% had positive results when written instructions emphasized listing only current symptoms. Women coming to the clinic because of a current medical concern or problem did have higher rates of positive SI results, as did non-white women (p < 0.05). Acceptability by providers was high. Patients could independently complete the SI in under 5 minutes. One patient with a positive SI was diagnosed with ovarian cancer and none with a negative SI developed cancer. Interpretation: A quick paper and pencil form can be used to identify women with symptoms potentially indicative of ovarian cancer. Use of such a form for ovarian cancer screening purposes is acceptable to most women and providers in a primary care clinic setting.

基质细胞衍生因子在不同的急性髓系白血病细胞系的迁移、黏附和细胞凋亡中的生物学作用

本研究探讨基质细胞衍生因子(stromal cell derived factor 1,SDF-1)在急性髓系白血病(AML)细胞的迁移、黏附和细胞凋亡中的生物学作用及有关的信号转导。采用流式细胞术检测AML的细胞系KG1a、ML1、U937细胞表面标记物的表达;以免疫荧光技术检测SDF-1对肿瘤细胞膜表面分子的影响;通过微孔细胞转移实验检测SDF-1对AML细胞的趋化作用及磷脂酰肌醇3激酶(PI3K)在趋化过程中的作用;用蛋白免疫印记技术检测PI3K信号途径有关的细胞凋亡分子BCL-XL在SDF-1活化此途径后的变化。结果表明:3种AML细胞系不同程度表达CD34(KG1a=95.6%、ML1=4.6%、U937=4.8%)、CD45(KG1a=98.3%、U937=97.5%、ML1=17.8%)、CXCR4(ML1=85.4%、U937=43.6%、KG1a=3.8%)、ICAM(KG1a=75.8%、U937=41.8%、ML1=46.3%)。SDF-1能促进CXCR4高表达的ML1和U937细胞在基质细胞的黏附并能够诱导此类细胞的迁移,上述作用被G蛋白抑制剂pertussis toxin(PTX)、PI3K抑制剂渥曼青霉素(wortmannin)明显抑制;而对CXCR4低表达的KG1a细胞则无上述作用。SDF通过此途径还促进肿瘤细胞存活;此作用同样可被PI3K抑制剂明显抑制,加用wortman-nin后促肿瘤细胞调亡显著增加。蛋白免疫印记检测phospho-AKT、BCL-XL显示,在SDF组明显增强,加用PTX、wortmannin组则减弱。结论:SDF-1能触发CXCR4高表达的ML1和U937细胞的极化形态的建立及诱导黏附分子的重新分布,从而通过PI3K信号途径促进此类AML细胞的迁移,减少肿瘤细胞的调亡,而对CXCR4低表达的KG1a细胞则无上述作用。上述作用可以被PI3K信号途径阻断剂和G蛋白抑制剂所阻断。

核技术应用研究中的蒙特卡罗计算问题

本文简单介绍了蒙特卡罗方法及其特点;重点叙述了蒙特卡罗方法在几个核技术领域中的应用;讲述了所使用的蒙特卡罗模拟方法;介绍了几个常用的蒙特卡罗方法的软件;给出了一个应用实例。

三氧化二砷和肿瘤坏死因子相关凋亡诱导配体诱导的髓系恶性细胞系P15^(ink4b)表达

目的:观察骨髓增生异常综合征(MDS)髓系原始细胞系MDS-L及髓系白血病细胞系ML1经不同剂量和不同时间的三氧化二砷(As2O3)和肿瘤坏死因子相关凋亡诱导配体(TRAIL)处理后的抑癌基因P15ink4b变化。并研究DNA甲基化转移酶DNMT1在P15ink4b变化中的可能作用。方法:体外培养的MDS-L和ML1细胞经9种不同浓度的药物处理(As2O31 mmol/L;2 mmol/L;5 mmol/L;TRAIL 100μg/L;300μg/L;500μg/L;As2O31 mmol/L加Trail 100μg/L;As2O32 mmol/L加TRAIL 300μg/L;As2O35 mmol/L加TRAIL 500μg/L),在24 h、48 h和72 h后收获细胞。未经药物处理的细胞和药物处理后收获的细胞均提取总RNA,经半定量RT-PCR检测P15ink4bmRNA表达。对MDS-L细胞还同时检测DNMT1表达;正常人和5例MDS病例的P15ink4b和DNMT1检测作为对照。结果:未经处理的MDS-L和ML1细胞基本不表达P15ink4b,药物处理后P15ink4b表达增强;药物诱导MDS-L细胞表达P15ink4b的作用强于ML1细胞;未经处理的MDS-L和ML1细胞高表达DNMT1,药物处理24 h后DNMT1不同程度下降,但DNMT1表达状况与P15ink4b表达增强不显示相关性。结论:As2O3和(或)TRAIL处理能促进髓系恶性细胞抑癌基因P15ink4b表达,但并非主要通过抑制DNMT1功能而起作用。

基于住院病案首页数据的全国部分医院心血管临床专科评估探索

目的运用“基于住院病案首页数据的心血管临床专科评估框架”,对全国部分医院的心血管临床专科进行评估。方法梳理112所医院心血管专科重点疾病和重点手术操作的编码情况,计算评估框架中的各个指标,根据医院纳入标准,运用基于数据的多指标综合评价方法,对医院进行打分排序。结果112所医院2010—2012年心血管疾病患者出院人次、重点疾病和重点手术/操作缺失数量均呈偏态分布。按照综合评价医院的纳入标准共56所医院纳入排序,前十位是YN05、SD04、BJ14、SH02、ZJ01、HN01、SX09、YN08、SD01、SX08。重点疾病和重点手术操作均完整的医院共12所,其排序是:BJ14、SH02、HN02、BJ01、TJ01、SH05、SC01、NA03、GD02、SH08、YN03、HL01。本研究综合评价的56所医院中,有30所在国家公布的名单之内,26所不在国家公布的名单之内。结论运用“基于住院病案首页数据的心血管临床专科评估框架”进行心血管临床专科评估是科学、可行的,为专科评估方法提供了新的思路,为专科对口支援建设提供了数据支持。

数字X射线骨密度检测系统前臂桡骨测量结果的评估

目的对比研究数字X射线骨密度检测系统和双能X线吸收检测法(dual-energy X-ray absorptiometry,DXA)检测桡骨骨密度(bone mineral density,BMD)两种不同测量方法的精确性和准确性。方法在浙江省人民医院用数字X射线骨密度检测系统及DXA对34名受试者的桡骨远端1/3处各测量2次,并对两种不同测量方法的精确性、准确性进行统计学分析。结果本研究中的34名受试者年龄31～81岁,平均年龄(55. 0±13. 3)岁,采用数字X射线骨密度检测系统测量的均方误差及均方变异系数分别为(0. 015 g/cm^2及1. 7%),均小于DXA的测量结果 (0. 019 g/cm^2及2. 1%)。两种检测方法检测的BMD值之间差异无统计学意义(P>0. 05)。结论数字X射线骨密度检测系统测量同DXA测量结果相似,可用于临床前臂桡骨骨密度测量和评估。

疾病经济负担研究综述

随着经济和科技的不断发展以及医疗卫生费用占GDP比重的不断增大,各国政府及学者们将越来越重视疾病经济负担研究,以合理配置医疗卫生资源及科学控制医疗费用和疾病经济负担。本文对不同时期的疾病经济负担研究的主要内容、方法、特点及局限性进行综述并对未来疾病负担研究进行展望。

Colostomy is a simple and effective procedure for severe chronic radiation proctitis

AIM: To assess the efficacy and safety of diverting colostomy in treating severe hemorrhagic chronic radiation proctitis(CRP). METHODS: Patients with severe hemorrhagic CRP who were admitted from 2008 to 2014 were enrolled into this study. All CRP patients were diagnosed by a combination of pelvic radiation history, clinical rectal bleeding, and endoscopic findings. Inclusion criteria were CRP patients with refractory bleeding with moderate to severe anemia with a hemoglobin level < 90 g/L. The study group included patients who were treated by diverting colostomy, while the control group included patients who received conservative treatment. The remission of bleeding was defined as complete cessation or only occasional bleeding that needed no further treatment. The primary outcome was bleeding remission at 6 mo after treatment. Quality of life beforetreatment and at follow-up was evaluated according to EORTC QLQ C30. Severe CRP complications were recorded during follow-up.RESULTS: Forty-seven consecutive patients were enrolled, including 22 in the colostomy group and 27 in the conservative treatment group. When compared to conservative treatment, colostomy obtained a higher rate of bleeding remission(94% vs 12%), especially in control of transfusion-dependent bleeding(100% vs 0%), and offered a better control of refractory perianal pain(100% vs 0%), and a lower score of bleeding(P < 0.001) at 6 mo after treatment. At 1 year after treatment, colostomy achieved better remission of both moderate bleeding(100% vs 21.5%, P = 0.002) and severe bleeding(100% vs 0%, P < 0.001), obtained a lower score of bleeding(0.8 vs 2.0, P < 0.001), and achieved obvious elevated hemoglobin levels(P = 0.003), when compared to the conservative treatment group. The quality of life dramatically improved after colostomy, which included global health, function, and symptoms, but it was not improved in the control group. Pathological evaluation after colostomy found diffused chronic inflammation cells, and massive fibrosis collagen depositions under the rectal wall, which revealed potential fibrosis formation. CONCLUSION: Diverting colostomy is a simple, effective and safe procedure for severe hemorrhagic CRP. Colostomy can improve quality of life and reduce serious complications secondary to radiotherapy.

劳埃晶体学时代的到来

近年来 ,人们对古老的劳埃衍射技术重新产生了浓厚的兴趣。这主要是因为世界各地新的同步辐射光源的建成;各种先进的插入件,诸如波形器(wiggler)、波荡器(undulator)的飞速发展 ;以及利用这类光源通过时间分辨晶体学来研究分子结构动态变化的前景。在过去的十年中 ,理论研究已经阐明了多波长衍射几何学的特征 ,在很大程度上加深了我们对劳埃法的认识。劳埃数据处理方法及其软件开发也因此有所创新。曾在相当长的时间内限制这项技术应用的劳埃数据处理中的大部分问题现在已经得到解决 ;同步辐射光源 ,束线光学器件及X射线探测器等方面也都取得了显著的进步。静态劳埃实验得到的结构因子振幅在质量上已同单波长数据相当。晶体中反应易于启动的时间分辨劳埃实验已经开始在一系列生物分子体系中得到成功的实践。由此得到的关于结构动力学的信息是任何其它传统的衍射方法所无能为力的。这些静态的及时间分辨的实验说明了劳埃法已经开始走向成熟 ,并指明了今后发展的方向 ,即对晶体的镶嵌度和劳埃衍射点的相应能量宽度的正确处理、扩散散射的考虑、时间分辨实验中低浓度瞬态中间物结构的测定等等。