New perspectives on robotic pancreaticoduodenectomy:An analysis of the National Cancer Database

BACKGROUND Pancreatic ductal adenocarcinoma is a common malignancy.Despite all advancements,the prognosis remains,poor with an overall 5-year survival of only 10.8%.Recently,a robotic platform has become an attractive tool for treating pancreatic cancer(PC).While recent studies indicated improved lymph node(LN)harvest during robotic pancreaticoduodenectomy(PD),data on long-term outcomes are insufficient.AIM To evaluate absolute LN harvest during PD.Secondary outcomes included evaluating the association between LN harvest and short-and long-term oncological outcomes for three different surgical approaches.METHODS We conducted an analysis of the National Cancer Database,including patients diagnosed with PC who underwent open,laparoscopic,or robotic PD in 2010-2018.One-way analysis of variance was used to compare continuous variables,chi-square test-for categorical.Overall survival was defined as the time between surgery and death.Median survival time was estimated with the Kaplan-Meier method,and groups were compared with the Wilcoxon test.A Cox proportional hazards model was used to assess the association of covariates with survival after controlling for patient characteristics and procedure type.RESULTS 17169 patients were included,8859(52%)males;mean age 65;14509(85%)white.13816(80.5%)patients had an open PD,2677(15.6%)and 676(3.9%)-laparoscopic and robotic PD respectively.Mean comorbidity index(Charlson-Deyo Score)0.50.On average,18.84 LNs were harvested.Mean LN harvest during open,laparoscopic and robotic PD was 18.59,19.65 and 20.70 respectively(P<0.001).On average 2.49 LNs were positive for cancer and did not differ by the procedure type(P=0.26).Vascular invasion was noted in 42.6%of LNs and did differ by the approach:42.1%for open,44.0%for laparoscopic and 47.2%for robotic PD(P=0.015).Median survival for open PD was 26.1 mo,laparoscopic-27.2 mo,robotic-29.1 mo(P=0.064).Survival was associated with higher LN harvest,while higher number of positive LNs was associated with higher mortality.CONCLUSION Our study suggests that robotic PD is associated with increased intraoperative LN harvest and has comparable short-term oncological outcomes and survival compared to open and laparoscopic approaches.

Comparative effectiveness of immunotherapy and chemotherapy in patients with metastatic colorectal cancer stratified by microsatellite instability status

BACKGROUND Immunotherapy have demonstrated promising outcomes in patients with high microsatellite instability(MSI)(MSI-H)metastatic colorectal cancer.However,the comparative effectiveness of Immunotherapy and chemotherapy for patients with low MSI(MSI-L),and microsatellite stable(MSS)metastatic colorectal cancer remains unclear.AIM To investigate immunotherapy vs chemotherapy for treatment of MSI-L/MSS metastatic colorectal cancer,and to evaluate the success of immunotherapy against chemotherapy in managing MSI-H metastatic colorectal cancer during a follow-up of 50 months.METHODS We conducted a retrospective cohort study using the National Cancer Database(NCDB)to evaluate the overall survival(OS)of patients with metastatic colorectal cancer treated with immunotherapy or chemotherapy.The study population was stratified by MSI status(MSI-H,MSI-L,and MSS).Multivariable Cox proportional hazard models were used to assess the association between treatment modality and OS,adjusting for potential confounders.RESULTS A total of 21951 patients with metastatic colorectal cancer were included in the analysis,of which 2358 were MSI-H,and 19593 were MSI-L/MSS.In the MSI-H cohort,immunotherapy treatment(n=142)was associated with a significantly improved median OS compared to chemotherapy(n=860).After adjusting for potential confounders,immunotherapy treatment remained significantly associated with better OS in the MSI-H cohort[adjusted hazard ratio(aHR):0.57,95%confidence interval(95%CI):0.43-0.77,P<0.001].In the MSS cohort,no significant difference in median OS was observed between immunotherapy treatment and chemotherapy(aHR:0.94,95%CI:0.69-1.29,P=0.715).CONCLUSION In this population-based study using the NCDB,immunotherapy treatment was associated with significantly improved OS compared to chemotherapy in patients with MSI-H metastatic colorectal cancer,but not in those with MSI-L/MSS metastatic colorectal cancer.Further studies are warranted to determine the optimal therapeutic approach for patients with MSI-L/MSS metastatic colorectal cancer.

LipoCol Forte capsules reduce the risk of liver cancer:A propensity score-matched,nationwide,population-based cohort study

BACKGROUND Liver cancer is among the top five most common cancers globally. Lipid-lowering drugs such as statins can lower the risk of liver cancer, but may also cause liver damage. LipoCol Forte capsules(LFC), a red yeast rice product, have demonstrated significant antihypercholesterolemic effects and a good safety profile in clinical studies.AIM To evaluate whether LFC lowers the risk of liver cancer in adults in this propensity score-matched, nationwide, population-based cohort study.METHODS We used data from Taiwan’s National Health Insurance Research Database, which includes electronic medical records for up to 99.99% of Taiwan’s population. LFC users and LFC non-users were matched 1:1 by propensity scores between January 2010 and December 2017. All had followup data for at least 1 year. Statistical analyses compared demographic distributions including sex, age, comorbidities, and prescribed medications. Cox regression analyses estimated adjusted hazard ratios(aHRs) after adjusting for potential confounders.RESULTS We enrolled 33231 LFC users and 33231 non-LFC users(controls). No significant differences between the study cohorts were identified regarding comorbidities and medications [standardized mean difference(SMD) < 0.05]. At follow-up, the overall incidence of liver cancer was significantly lower in the LFC cohort compared with controls [aHR 0.91;95% confidence interval(CI): 0.86-0.95;P < 0.001]. The risk of liver cancer was significantly reduced in both females(aHR 0.87;95%CI: 0.8-0.94;P < 0.001) and males(aHR 0.93;95%CI: 0.87-0.98;P < 0.01) in the LFC cohort compared with their counterparts in the non-LFC cohort. The antitumor protective effects applied to patients with comorbidities(including hypertension, ischemic stroke, diabetes mellitus, hyperlipidemia, hepatitis B infection and hepatitis C infection). Those using LFC for more than 84 drug days had a 0.64-fold lower risk of liver cancer compared with controls(P < 0.001). Compared with controls, the risk of developing liver cancer in the LFC cohort progressively decreased over time;the lowest incidence of liver cancer occurred in LFC users followed-up for more than 6 years(27.44 vs 31.49 per 1,000 person-years;aHR 0.75;95%CI: 0.68-0.82;P < 0.001).CONCLUSION This retrospective cohort study indicates that LFC has a significantly protective effect on lowering the risk of liver cancer, in a dose-dependent and time-dependent manner.

Carcinosarcoma of the nasal cavity and paranasal sinuses:Review of the national cancer database

Background:Carcinosarcomas are rare,aggressive malignancies that can arise in the nasal cavity and paranasal sinuses.There are limited outcome data available.Accordingly,we sought to use the National Cancer Database(NCDB)to characterize patient demographics and outcomes.Method:A retrospective analysis of the NCDB from 2004 to 2016 for patients with sinonasal carcinosarcoma was conducted.Results:Thirty patients were included.The patients were predominantly male(n=20),white(n=23),and privately insured(n=15),with an average age of 62.4 years.The nasal cavity was the most common subsite(n=14),followed by the maxillary sinus(n=8).Most patient were treated with surgery followed by radiation(n=23),with the remaining undergoing surgery alone(n=4),radiation alone(n=2),or no treatment(n=1).One-third(n=10)received adjuvant chemotherapy.The 1-and 5-year overall survival(OS)in the cohort were 79.2%and 43.3%,respectively.Univariate log-rank testing showed OS varied based on intervention(P<0.029),sex(P<0.042),and age(P<0.025),while on multivariate analysis none of these factors independently predicted OS.Conclusions:We describe the demographics and presenting features of a national cohort of sinonasal carcinosarcoma patients.Future research is needed to identify predictors of overall survival,and to assess the optimal roles for radiation and systemic chemotherapy.

Data mining in clinical big data:the frequently used databases,steps,and methodological models

Many high quality studies have emerged from public databases,such as Surveillance,Epidemiology,and End Results(SEER),National Health and Nutrition Examination Survey(NHANES),The Cancer Genome Atlas(TCGA),and Medical Information Mart for Intensive Care(MIMIC);however,these data are often characterized by a high degree of dimensional heterogeneity,timeliness,scarcity,irregularity,and other characteristics,resulting in the value of these data not being fully utilized.Data-mining technology has been a frontier field in medical research,as it demonstrates excellent performance in evaluating patient risks and assisting clinical decision-making in building disease-prediction models.Therefore,data mining has unique advantages in clinical big-data research,especially in large-scale medical public databases.This article introduced the main medical public database and described the steps,tasks,and models of data mining in simple language.Additionally,we described data-mining methods along with their practical applications.The goal of this work was to aid clinical researchers in gaining a clear and intuitive understanding of the application of data-mining technology on clinical big-data in order to promote the production of research results that are beneficial to doctors and patients.

Extent of lymphadenectomy has no impact on postoperative complications after gastric cancer surgery in Sweden

Objective： Curative gastric cancer surgery entails removal of the primary tumor with adequate margins including regional lymph nodes. European randomized controlled trials with recruitment in the 1990＇s reported increased morbidity and mortality for D2 compared to D 1. Here, we examined the extent of lymphadenectomy during gastric cancer surgery and the associated risk for postoperative complications and mortality using the strengths of a population-based study. Methods： A prospective nationwide study conducted within the National Register of Esophageal and Gastric Cancer. All patients in Sweden from 2006 to 2013 who underwent gastric cancer resections with curative intent were included. Patients were categorized into DO, D I, or D I ＋/D2, and analyzed regarding postoperative morbidity and mortality using multivariable logistic regression. Results： In total, 349 （31.7%） patients had a DO, 494 （44.9%） DI, and 258 （23.4%） DI＋/D2 lymphadenectomy. The 30-d postoperative complication rates were 25.5%, 25.1% and 32.2 % （DO, D I and D1 ＋/D2, respectively）, and 90-d mortality rates were 8.3%, 4.3 % and 5.8%. After adjustment for confounders, in mukivariable analysis, there were no significant differences in risk for postoperative complications between the lymphadenectomy groups. For 90-d mortality, there was a lower risk for D1 vs. DO. Conclusions： The majority of gastric cancer resections in Sweden have included only a limited lymphadenectomy （DO and DI）. More extensive lymphadenectomy （DI＋/D2） seemed to have no impact on postoperative morbidity or mortality.

Impact of Diabetes Mellitus on the Treatment Outcomes of Chemotherapy in Women with Breast Cancer——A Population-Based Prospective Cohort Study

There are few population-based data in investigating the impact of diabetes on chemotherapy adverse effects and treatment outcomes of non-metastatic breast cancer. The purpose of this study is to evaluate whether diabetes affects the patterns of use in chemotherapy, toxic effects of chemotherapy, and treatment outcomes for non-metastatic breast cancer in Taiwan. The study results can provide physicians for making a decision whether or not to use chemotherapy based on the individual patients＇ condition.

Predictors of nodal metastasis in sinonasal squamous cell carcinoma:A national cancer database analysis

Objective:We present the largest population based study of sinonasal squamous cell carcinoma(SCC)to identify risk factors for presentation with nodal metastasis.Methods:The National Cancer Database(NCDB)was used for this study.Location codes corresponding to the nasal cavity and paranasal sinuses and histology codes representing SCC malignancy were queried.Logistic regression analysis was performed to identify factors associated with presentation with nodal metastasis.Results:6448 cases met inclusion criteria.Nodal metastasis at presentation was seen in 13.2%of patients,with the sinus subsite(19.3%)being a significant risk factor for nodal metastasis at presentation when compared to the nasal cavity(7.9%).Logistic regression analysis showed black,uninsured and Medicaid patients were more likely than white and privately insured patients,respectively,to present with nodal metastasis.Conclusions:In sinonasal SCC,the sinus subsite has a significantly increased risk of nodal metastasis compared to the nasal cavity.Black race,uninsured and Medicaid patients are more likely to have nodal metastasis at presentation.

基于监测、流行病学和结果数据库分析管腔A型乳腺癌辅助化疗效果

目的基于美国国立癌症研究所(NCI)的监测、流行病学和结果数据库(SEER数据库)观察管腔(Luminal)A型早期乳腺癌辅助化疗的临床疗效。方法应用SEER数据库筛选出207404例接受过手术治疗的Luminal A型早期乳腺癌患者的资料,根据是否接受辅助化疗将患者分为化疗组与未化疗组,并根据临床病理特征进行亚组分型。比较2组患者的生存时间与累积风险曲线。结果Luminal A型早期乳腺癌患者总体预后良好,患者性别、年龄、种族、病理类型以及病理分级对Luminal A型早期乳腺癌化疗决策的影响不大,而临床分期、淋巴结转移N分期对患者的化疗决策有一定影响。结论在缺乏多基因检测结果的情况下,临床工作中可考虑将淋巴结转移N1mi期纳入Luminal A型早期乳腺癌患者免除辅助化疗的参考指标。

治疗肺癌化疗期专利中药复方的用药规律探讨

【目的】挖掘国家专利数据库中肺癌化疗期专利中药复方的用药规律。【方法】通过"国家知识产权局"网站检索关于肺癌化疗期的中药复方专利,将中药录入中医传承辅助平台(V2.5)中,统计药物频次,进行药物关联组合及关联规则分析,并提取内在核心组合和新方组合。【结果】共录入89首处方,涉及390味中药。其中用药频次较高的有黄芪、甘草、白花蛇舌草、麦冬、半枝莲、人参、白术、茯苓、当归、川贝母、半夏、瓜蒌等;常用药物组合有"白花蛇舌草,半枝莲""黄芪,白术""黄芪,甘草""人参,黄芪"等,频度较高的药物关联规则有"白术→黄芪"和"半枝莲→白花蛇舌草";并挖掘出内在核心组合8个以及新方4首。【结论】治疗肺癌化疗期以扶正固本、兼顾祛邪为原则。扶正以益气养阴、固肾健脾为主,尤以补益肺脾气阴为核心;祛邪则在解毒抗癌的基础上,以活血化瘀、理气化痰为基本治法。各专利中药复方的用药具有以下特点:补气健脾以培土生金,祛瘀化痰以散结除积,清热解毒以抗癌消瘤,养阴生津以补虚清燥,固本补肾以填精益髓疗虚。

Retrospective review of total neoadjuvant therapy

BACKGROUND Neoadjuvant chemoradiotherapy(nCRT)followed by resection and postoperative multi-agent chemotherapy(maChT)is the standard of care for locally advanced rectal cancer.Using this approach,maChT administration can be delayed for several months,leading to concern for distant metastases.To counteract this,a novel treatment approach known as total neoadjuvant therapy(TNT)has gained popularity,in which patients receive both maChT and nCRT prior to resection.We utilized the National Cancer Database to examine temporal trends in TNT usage,and any potential effect on survival.AIM To study the temporal trends in the usage of TNT and evaluate its efficacy compared to neoadjuvant chemoradiation.METHODS We queried the National Cancer Database for patients with locally advanced rectal cancer,Stage II-III,from 2004-2015 treated with nCRT or TNT.TNT was defined as maChT initiated≥90 d prior to nCRT initiation.Overall survival was calculated from the date of diagnosis to the date of last contact or death using Kaplan-Meier curves to present the cumulative probability of survival,with logrank statistics to assess significance.Multivariable cox regression was used to identify predictors of survival and propensity score analysis accounted for bias.RESULTS We identified 9066 eligible patients,with 8812 and 254 patients receiving neoadjuvant chemoradiation followed by maChT and TNT,respectively.Nodal involvement,stage III disease,and treatment in recent years were predictive of TNT use.There was greater use of TNT with more advanced stage,specifically>1 node involved(odds ratio[OR]=2.88,95%confidence interval[CI]:2.11-3.93,P<0.01)and stage III disease(OR=2.88,95%CI:2.11-3.93,P<0.01).From 2010 to 2012 the use of TNT increased(OR=2.41,95%CI:1.27-4.56,P<0.01)with a greater increase from 2013 to 2015(OR=6.62,95%CI:3.57-12.25,P<0.01).Both the TNT and neoadjuvant chemoradiation arms had a similar 5-year survival at 76%and 78%respectively.Multivariable analysis with propensity score demonstrated that increased age,high comorbidity score,higher grade,African American race,and female gender had worse overall survival.CONCLUSION Our data demonstrates a rising trend in TNT use,particularly in patients with worse disease.Patients treated with TNT and nCRT had similar survival.Randomized trials evaluating TNT are underway.

Healthcare utilization and costs associated with gastroparesis

AIM To use a national database of United States hospitals to evaluate the incidence and costs of hospital admissions associated with gastroparesis.METHODS We analyzed the National Inpatient Sample Database(NIS)for all patients in whom gastroparesis(ICD-9 code:536.3)was the principal discharge diagnosis during the period,1997-2013.The NIS is the largest publicly available all-payer inpatient care database in the United States.It contains data from approximately eight million hospital stays each year.The statistical significance of the difference in the number of hospital discharges,length of stay and hospital costs over the study period was determined by regression analysis.RESULTS In 1997,there were 3978 admissions with a principal discharge diagnosis of gastroparesis as compared to16460 in 2013(P<0.01).The mean length of stay for gastroparesis decreased by 20%between 1997 and 2013from 6.4 d to 5.1 d(P<0.001).However,during this period the mean hospital charges increased significantly by 159%from$13350(after inflation adjustment)per patient in 1997 to$34585 per patient in 2013(P<0.001).The aggregate charges(i.e.,"national bill") for gastroparesis increased exponentially by 1026%from$50456642±4662620 in 1997 to$568417666±22374060 in 2013(P<0.001).The percentage of national bill for gastroparesis discharges(national bill for gastroparesis/total national bill)has also increased over the last 16 years(0.0013%in 1997 vs 0.004%in2013).During the study period,women had a higher frequency of gastroparesis discharges when compared to men(1.39/10000 vs 0.9/10000 in 1997 and 5.8/10000vs 3/10000 in 2013).There was a 6-fold increase in the discharge diagnosis of gastroparesis amongst type 1 DM and 3.7-fold increase amongst type 2 DM patients over the study period(P<0.001).CONCLUSION The number of inpatient admissions for gastroparesis and associated costs have increased significantly over the last 16 years.Inpatient costs associated with gastroparesis contribute significantly to the national healthcare bill.Further research on cost-effective evaluation and management of gastroparesis is required.

纳米给药系统在肿瘤靶向治疗中的应用

背景:纳米材料是抗肿瘤药物的理想载体,具有重要的科学价值和应用价值,为临床抗肿瘤提供了新的有效手段。目的:系统评价纳米给药系统在肿瘤靶向治疗的基础研究及临床应用。方法:以"nanoparticle,cancer,drug delivery system,nanotube,nanosphere"为关键词,计算机检索北美临床试验注册中心及Web of Science数据库2000-01-01/2012-12-31发表的纳米给药系统在肿瘤靶向治疗相关临床试验注册项目及文献。根据纳入与排除标准筛选文献,将检索结果以注册号、注册题目、项目状态、干预措施、试验的申办者、试验的疾病种类导出进行评价质量及文献分析。结果与结论:①北美临床试验注册中心关于纳米给药系统在肿瘤靶向治疗的相关临床试验研究开始于1999年,共检索到注册项目489项,经查阅后,共有429项纳入了分析。美国注册的纳米载体肿瘤靶向给药临床试验项目最多,共112项,其次为加拿大24项。中国注册的临床试验有22项,其中大陆注册8项,香港地区注册4项,台湾地区注册10项。研究的注册数量2003年跌至谷底,只有5项注册项目,之后数量大幅度升高,在2008年注册项目数量达到顶峰,为56项。2008年后,注册的项目数量处于波动状态。②北美临床试验注册中心纳米给药系统在肿瘤靶向治疗的相关临床试验项目样本量在1-2000之间,以50人以下的小样本研究为主。研究的肿瘤类型以乳腺癌为主,其次为内分泌腺瘤及淋巴瘤。③2000-01-01/2012-12-31在Web of Science数据库发表的纳米载体肿瘤靶向给药相关文章4497篇,其中,美国发文量占总数比重最大(66.42%),发表文章2987篇。高被引文章主要发表在Proceedings of the National Academy of Sciences of the United States of America(《美国科学院院刊》)。

Improving the quality of gastric cancer surgery:factors associated with positive resection margins for gastrectomy

Purpose:Positive margins after gastrectomy have been associated with poor patient prognosis.This study aimed to identify risk factors associated with margin-positive resections.Methods:The National Cancer Database was queried from 2004 to 2014 for all patients with gastric adenocarcinoma who underwent resection with curative intent and had known margin status.Univariable and multivariable logistic regression analysis was performed to identify variables associated with positive margins.Results:A total of 32,193 patients were identified who met study inclusion criteria,of which 11.8%(3786 patients)had a margin-positive resection.Tumor size>6 cm,T3 or T4 tumors,tumor location in the body of stomach or in multiple regions,signet ring cell histology,presence of lymphovascular invasion,positive lymph node involvement,and lack of neoadjuvant therapy were independently associated with an increased risk of positive margins.Conclusions:Advanced disease characteristics,aggressive tumor pathology,and absence of neoadjuvant therapy were associated with margin-positive resections.

年龄对转移性结直肠癌不同治疗方法的影响及预后研究

目的探讨年龄与转移性结直肠癌(mCRC)的治疗方式选择和预后的相关性。方法我们从美国国家癌症数据库(NCDB)中选择了2004~2014年mCRC的患者,总数为43977人,将患者分为三个年龄组:18~49岁、50~75岁和>75岁。分别描述了每个治疗类别的患者百分比,包括仅原发性肿瘤切除术(PTR)、仅化疗和PTR加化疗。在调整人口统计学和临床因素后,计算并比较不同年龄组和治疗组的限制平均生存时间(RMST)。结果18~49岁年龄组的大多数患者(61.8%)接受PTR联合化疗,50~75岁年龄组约有53.3%的患者接受PTR联合化疗,>75岁年龄组大约有34.7%接受PTR联合化疗。在研究期间,所有年龄组的mCRC患者,PTR加化疗组呈下降趋势,而仅化疗组呈上升趋势。与其他治疗方法相比,PTR加化疗在所有年龄组中的生存率最高。除了18~49岁组的患者外,化疗与仅PTR相比具有更高的生存时间。在接受PTR加化疗治疗的患者中,与其他治疗相比,18~49和50~75岁组的围手术期化疗的患者可以获得更长的生存期,但>75岁组的化疗与否和生存期无关。结论尽管mCRC患者PTR加化疗呈下降趋势,但是其在所有年龄组中显示出最大的生存获益。不同的年龄组在接受特定的MDT治疗后的获益存在差异。

基于国家专利数据库分析中药复方治疗大肠癌用药规律

目的基于国家专利数据库,挖掘近10年中药复方专利治疗大肠癌的用药规律。方法检索国家专利数据库,提取治疗大肠癌的中药复方专利,数据经筛选、录入、规范化处理等步骤后,建立治疗大肠癌的中药复方专利数据库,利用IBM SPSS Modeler和IBM SPSS Statistics软件进行中药使用频次分析、性味归经分析、关联分析及聚类分析。结果共获得97条复方专利,包含411味中药,其中核心中药为白术、白花蛇舌草、黄芪、甘草、半枝莲、茯苓等,药性以寒、温为主;药味以苦、甘为主;归经以脾经为主;聚类分析结果包含7类,关联性较强的对药包括白花蛇舌草-半枝莲、白术-莪术、黄芪-党参等。结论补虚法治疗大肠癌应以白术、黄芪、党参等健脾补虚药为主,攻实法以白花蛇舌草、半枝莲、莪术等清热解毒、活血化瘀药为主,同时可酌情配伍,攻补兼施,调补气血。