Borderline or locally advanced pancreatic adenocarcinoma: A single center experience on the FOLFIRINOX induction regimen

IntroductionThis study aimed to determine the impact of FOLFIRINOX neoadjuvant therapy on patients with non-metastatic borderline/locally advanced (BL/LA) pancreatic ductal adenocarcinoma (PDAC), in current practice.Material and methodsFrom 2010 to 2017, 258 patients with BL/LA PDAC from a single high-volume institution received FOLFIRINOX neoadjuvant treatment.ResultsThe 258 patients received a median number of 6 cycles of FOLFIRINOX (range, 3–16); 98 (38%) patients underwent curative surgery, and 160 (62%) continued medical treatment. A venous resection was performed in 57 patients (58%), and an arterial resection in 12 (12%). The postoperative 30- and 90-day mortality rates were 6.1% and 8.2%, respectively. Adjuvant chemotherapy was performed in 57 patients (59%). The median overall survival (OS) in patients who did (n = 98) or did not (n = 160) undergo surgical resection were 39 months and 19 months, respectively (P < 0.001). In resected patients, the ASA 3 score (P < 0.01), venous resection (P < 0.01), hemorrhage (P < 0.01), and R1 margin status (P = 0.03) were found to negatively influence the OS. The median OS was significantly higher in patients who did not require a venous resection (not reached vs. 26.5 months, P < 0.001).ConclusionsNeoadjuvant FOLFIRINOX provided a survival benefit in BL/LA PDAC patients, particularly in those who did not ultimately require venous resection.     

不同病理分级的胰腺神经内分泌肿瘤的MRI征象对比分析及“主胰管绕道征”的诊断价值探讨

目的:对比分析G1、G2级胰腺神经内分泌肿瘤（pNEN）的MRI征象，探讨“主胰管绕道征”的诊断价值。方法:收集32例pNEN患者的临床资料，以术后病理学检查为金标准，定量分析G1、G2级临床指标及影像学指标的差异，并着重分析pNEN与主胰管的关系。结果:32例患者中，病理分级G1、G2、G3级的患者分别有12例、16例、4例，分别以胰尾、胰头、胰颈为主要发生部位。与G1级神经内分泌瘤（NET）相比，G2级NET肿瘤直径显著增大，不规则形态的病灶增多，边缘模糊，生物学行为出现明显恶性倾向，主胰管扩张、胰腺外侵犯及淋巴结/肝转移的发生率升高。G1级NET的MRI平扫信号均质程度高于G2级（P＜0.05），但二者在增强MRI扫描的各个期象信号强度均无明显差异（P＞0.05）。28例NET患者中，22例（78.6%）出现主胰管绕道征；神经内分泌癌（NEC）患者无一例出现此征象。术前，28例NET的诊断准确率为78.6%（22/28），存在6例误诊，其中，3例误诊为胰腺癌，2例误诊为囊腺瘤（癌），1例误诊为胰腺假性囊肿。在原MRI诊断依据的基础上纳入“主胰管绕道征”，诊断准确率提高至89.3%（25/28），但仍存在3例误诊，其中2例误诊为囊腺瘤（癌），1例误诊为胰腺假性囊肿，排除了胰腺癌的误诊。结论:MRI对鉴别诊断良恶性pNEN有较高的准确性，但对部分G1与G2级NET仍存在一定的误诊率，主胰管绕道征可帮助减少出现胰腺癌误诊。     

首荟通便胶囊预防肝胆胰恶性肿瘤化疗后便秘的疗效观察

目的:探讨首荟通便胶囊预防肝胆胰恶性肿瘤化疗后便秘的临床疗效。方法:选取2016年8月至2018年8月河北医科大学第二医院肝胆外科收治的老年肝胆胰恶性肿瘤化疗患者80例作为研究对象,按照随机数字表法随机分为对照组和观察组,每组40例。对照组口服乳果糖口服液,观察组在对照组基础上加服首荟通便胶囊。治疗14 d后,比较2组的临床疗效。结果:中医病症临床疗效观察,对照组总有效率达到75%;观察组,总有效率达到90%,2组比较差异有统计学意义(P<0.05)。临床症状评分观察,对照组总有效率达到77.5%;观察组总有效率达到92.5%,2组比较差异有统计学意义(P<0.05)。排便评分(VAS评分)观察,治疗后对照组排便间隔时间和每次排便时间均长于观察组,2组VAS评分比较,差异均有统计学意义(P<0.05)。结论:首荟通便胶囊可以有效预防肝胆胰恶性肿瘤化疗后的便秘,有效缓解患者排便疼痛程度,减少排便时间,效果显著,值得临床推广。     

Biperiden and mepazine effectively inhibit MALT1 activity and tumor growth in pancreatic cancer

MALT1 is a key mediator of NF-κB signaling and a main driver of B-cell lymphomas. Remarkably, MALT1 is expressed in the majority of pancreatic ductal adenocarcinomas (PDACs) as well, but absent from normal exocrine pancreatic tissue. Following, MALT1 shows off to be a specific target in cancer cells of PDAC without affecting regular pancreatic cells. Therefore, we studied the impact of pharmacological MALT1 inhibition in pancreatic cancer and showed promising effects on tumor progression. Mepazine (Mep), a phenothiazine derivative, is a known potent MALT1 inhibitor. Newly, we described that biperiden (Bip) is a potent MALT1 inhibitor with even less pharmacological side effects. Thus, Bip is a promising drug leading to reduced proliferation and increased apoptosis in PDAC cells in vitro and in vivo. By compromising MALT1 activity, nuclear translocation of c-Rel is prevented. c-Rel is critical for NF-κB-dependent inhibition of apoptosis. Hence, off-label use of Bip or Mep represents a promising new therapeutic approach to PDAC treatment. Regularly, the Anticholinergicum Bip is used to treat neurological side effects of Phenothiazines, like extrapyramidal symptoms.     

激素受体阳性乳腺癌患者在不同内分泌治疗用药时间的类更年期症状及生命质量

目的探讨激素受体阳性(HR+)乳腺癌患者在不同内分泌治疗时间的类更年期症状和生命质量状况。方法采用横断面研究设计,收集2011—2017年就诊于四川省肿瘤医院经病理确诊的167例HR+乳腺癌患者,按内分泌治疗时间分为<12个月组、12~36个月组、>36个月组。应用改良Kupperman量表和乳腺癌生命质量测定量表(FACT-B)测量类更年期症状和生命质量。采用方差分析及χ2检验比较不同用药时间及用药类型患者的类更年期症状差异,采用协方差分析和多重线性回归分析不同用药时间患者的生命质量得分差异和类更年期症状对生命质量的影响。结果167例乳腺癌患者的类更年期症状得分为(14.5±7.6)分,现患率为87.4%(146/167),以失眠率最高(73.7%,123/167)。除失眠易激动外,选择性雌激素受体调节剂(SERM)使用者以潮热症状最多(64.8%,79/122),芳香化酶抑制剂使用者以骨关节痛症状最多(62.2%,28/45)。患者的FACT-B总得分为(104.5±15.5)分,达标率高达89.8%(150/167),但各维度状况参差不齐,以社会家庭及功能维度达标率最低,分别为73.0%(122/167)和50.9%(85/167)。<12个月组、12~36个月组和>36个月组患者的Kupperman总分分别为(15.0±1.3)分、(14.0±6.9)分和(14.5±7.4)分;FACT-B总得分分别为(102.7±17.8)分、(105.0±12.9)分和(105.6±16.7)分,差异均无统计学意义(均P>0.05)。多重线性回归分析结果显示,患者服用SERM类药物期间类更年期症状对生命质量存在负向影响,<12个月组、12~36个月组和>36个月组患者的标准偏回归系数分别为-0.67、-0.30和-0.50,影响程度在12~36个月组中最小。结论HR+乳腺癌患者回归社会、家庭和功能恢复情况较差,应重点关注。类更年期症状在内分泌治疗期间普遍存在,应积极处理以改善生命质量。     

luminal型乳腺癌患者戈舍瑞林用药依从性现状及影响因素分析

目的了解luminal型乳腺癌患者戈舍瑞林用药依从性情况，分析影响其依从性的相关因素。 方法根据纳入及排除标准，收集2015年1月至2017年12月重庆医科大学附属第一医院内分泌乳腺外科使用戈舍瑞林治疗的luminal型乳腺癌女性患者174例进行回顾性分析。中位随访时间16个月(范围：1～54个月)，完成随访154例，失访20例，失访率为11.5%(20/174)。采用问卷调查评价其用药依从性，使用χ²检验和Mann-Whitney U检验比较不同特征患者依从性的差异；用Logistic回归分析影响患者依从性的相关因素。将患者分为≤40岁(103例)和>40岁(51例)2个亚组，进行亚组分析。 结果在完成随访的154例患者中，依从性好82例(53.2%，82/154)，依从性差72例(46.8%，72/154)。≤40岁组患者中，55.3%(57/103)依从性好，而>40岁组患者中仅49.0%(25/51)依从性好。全部患者中，文化程度、医保类型、不良反应和是否了解疗程时间均与乳腺癌患者戈舍瑞林用药依从性有关(χ²＝13.586、13.042、7.880、14.251，P均<0.050)；Logistic回归分析结果显示：高中及以下学历、居民医保和不了解戈舍瑞林的疗程时间为影响依从性的危险因素(OR＝2.772，95%CI：1.243～6.183，P＝0.013；OR＝5.188，95%CI：1.383～19.465，P＝0.015; OR＝3.363，95%CI：1.645～6.878，P＝0.001)。亚组分析显示：文化程度、职业、医保类型和是否了解疗程时间是≤40岁患者戈舍瑞林用药依从性的影响因素(χ²＝15.992、5.978、7.701、10.376，P均<0.050)；不良反应及医保类型是>40岁患者用药依从性的影响因素(χ²＝4.763、7.471，P均<0.050)。Logistic回归分析表明：高中及以下文化程度和不了解疗程时间是≤40岁患者用药依从性的危险因素(OR＝5.126，95%CI：2.086～12.598，P<0.001; OR＝3.631, 95%CI：1.500～8.792，P＝0.004)；居民医保是>40岁患者用药依从性的危险因素(OR＝64.315，95%CI：2.513～1 646.042，P＝0.012)，不良反应是>40岁患者用药依从性的保护因素OR＝0.189，95%CI＝0.047～0.759，P＝0.019)。 结论luminal型乳腺癌患者戈舍瑞林用药依从性较差，文化程度、医保类型及是否了解疗程时间都可能影响患者的依从性。≤40岁组和>40岁组患者依从性有差异，且影响因素不同，建议对不同年龄患者用药采用不同的干预措施。     

一例分化型甲状腺癌患者健康管理全科医生教学案例分析

甲状腺癌已成为北京市增长较快的恶性肿瘤。本文通过介绍1例由全科医生首诊、术后连续随访4年的分化型甲状腺癌患者的诊疗经过，采用临床案例教学方法，重点关注甲状腺结节良恶性的鉴别，全科医生接诊甲状腺结节患者的诊治流程及对甲状腺癌患者术后长期监测、健康管理的内容，引导患者规范诊治，以期为逐步实现甲状腺癌患者个体化、不同风险分层的高质量管理，提高在职全科医生、全科医学专业住院医师规范化培训的学员对甲状腺结节、分化型甲状腺癌患者的规范诊治水平，提供参考。     

重楼皂苷D对人胰腺癌细胞增殖和凋亡的影响

重楼皂苷D(polyphyllin D)是重楼中的一种甾体皂苷单体,具有抗菌、镇痛、镇静、抗肿瘤等多种药理作用,但在胰腺癌中少有报道。该研究通过检测凋亡相关指标,探讨polyphyllin D对人胰腺癌Panc-1细胞增殖和凋亡的影响及相关作用机制。采用CCK-8法检测不同浓度的(0,1,2,3,4,5μg·μL-1)polyphyllin D分别处理胰腺癌Panc-1细胞24,48,72 h后,观察对细胞增殖的影响。采用流式细胞术对细胞周期、细胞线粒体膜电位(mitochondrial membrane protential,MMP)进行检测,Annexin-V-FITC/PI双染法检测细胞凋亡情况,Western blot法检测细胞色素C (cytochrome C,Cyto C),Bax,Bcl-2,cleaved caspase-3,cleaved caspase-9的蛋白表达情况。结果表明,与对照组相比,polyphyllin D能够时间和浓度依赖性地抑制Panc-1细胞的增殖活性。流式细胞术检测显示polyphyllin D能浓度依赖性使细胞阻滞于S期和G2/M期,MMP明显降低,细胞凋亡率随polyphyllin D作用浓度增加而增加。Western blot结果显示,polyphyllin D能浓度依赖性地上调Bax,Cyto C,cleaved caspase-3和cleaved caspase-9的蛋白表达水平,下调Bcl-2的蛋白表达水平。以上研究结果提示,polyphyllin D能抑制胰腺癌Panc-1细胞的增殖,其机制可能与阻滞细胞的生长周期以及通过线粒体途径诱导细胞的凋亡相关。     

Mailed fecal immunochemical test outreach for colorectal cancer screening: Summary of a Centers for Disease Control and Prevention–sponsored Summit

Uptake of colorectal cancer screening remains suboptimal. Mailed fecal immunochemical testing (FIT) offers promise for increasing screening rates, but optimal strategies for implementation have not been well synthesized. In June 2019, the Centers for Disease Control and Prevention convened a meeting of subject matter experts and stakeholders to answer key questions regarding mailed FIT implementation in the United States. Points of agreement included: 1) primers, such as texts, telephone calls, and printed mailings before mailed FIT, appear to contribute to effectiveness; 2) invitation letters should be brief and easy to read, and the signatory should be tailored based on setting; 3) instructions for FIT completion should be simple and address challenges that may lead to failed laboratory processing, such as notation of collection date; 4) reminders delivered to initial noncompleters should be used to increase the FIT return rate; 5) data infrastructure should identify eligible patients and track each step in the outreach process, from primer delivery through abnormal FIT follow-up; 6) protocols and procedures such as navigation should be in place to promote colonoscopy after abnormal FIT; 7) a high-quality, 1-sample FIT should be used; 8) sustainability requires a program champion and organizational support for the work, including sufficient funding and external policies (such as quality reporting requirements) to drive commitment to program investment; and 9) the cost effectiveness of mailed FIT has been established. Participants concluded that mailed FIT is an effective and efficient strategy with great potential for increasing colorectal cancer screening in diverse health care settings if more widely implemented.