Caspase-1 p20水平预测局部进展期直肠癌新辅助放疗敏感性的临床意义

目的 探讨含半胱氨酸的天冬氨酸蛋白水解酶1(Caspase-1)活化物Caspase-1 p20水平与局部进展期直肠癌新辅助放疗敏感性的关系,评价Caspase-1 p20水平预测术前新辅助放疗效果的价值。方法 收集本院2017年9月至2020年12月接受新辅助放化疗联合手术治疗的直肠癌患者55例,免疫组化法检测术后标本中的Caspase-1 p20水平,根据肿瘤退缩分级(TRG)评价新辅助放疗敏感性,分析Caspase-1 p20水平变化与临床病理特征和放疗敏感性的关系。结果 55例患者放疗敏感(TRG0+TRG1) 26例、放疗抵抗(TRG2+TRG3) 29例,Caspase-1 p20在30例肿瘤组织中呈低水平、25例呈高水平。直肠癌组织的Caspase-1 p20水平与放疗敏感性、新辅助放化疗的术后病理T分期和肿瘤直径有关(P<0.05)。Caspase-1 p20高水平者的肿瘤退缩差、对放疗抵抗,相关性分析证实Caspase-1 p20水平与TRG分级呈正相关(r²=0.44)。多因素分析示,Caspase-1 p20水平是放疗抵抗的独立风险因素...     

Ⅱ、Ⅲ期直肠癌新辅助放化疗与手术间隔时间对术后病理及临床疗效的影响

目的:探讨局部晚期直肠癌新辅助放化疗结束与手术的间隔时间对病理及临床疗效的影响。方法:回顾性分析2010年1月至2013年7月间接受新辅助放化疗随后行根治性手术的78例初治局部晚期直肠癌患者的临床资料。根据新辅助治疗结束至手术的间隔时间中位数分为两组,A组为新辅助放化疗结束后﹤7周手术治疗38例;B组为≥7周手术治疗40例。全部患者采用三维适形调强放疗,2Gy/1次, 5次/1周,总50Gy,同步行氟尿嘧啶为基础的化疗,比较两组患者肿瘤病理退缩分级（TGR）、降期率、手术并发症发生率、局部复发率、远处转移率和生存率。结果:TRG1、TRG2、TRG3、TRG4（PCR）A组分别为 9例、7例、10例、6例,B组分别为9例、9例、12例、8例（P=0.614）;T分期降期率A组63.2%,B组52.5%（P=0.368）,N分期降期率A组39.5%,B组55%（P=0.039）;手术并发症发生率A组18.4%,B组20%（P=0.550）;3年复发率A组7.9%,B组10%（P=0.745);远处转移率A组13.2%,B组10%（P=0.663）;3年生存率A组70.8%,B组84%（P=0.453）。结论:新辅助放化疗结束≥7周行手术,可以获得较高的淋巴结降期率,不增加手术难度和并发症发生率。     

功能成像技术对局部晚期直肠癌新辅助治疗预测与评估价值

对于局部晚期直肠癌,新辅助放化疗后行手术切除,再行术后辅助化疗,已发展为标准治疗模式。新辅助治疗可使肿瘤病灶发生不同程度的退缩,部分患者术后病理证实达到完全缓解,有助于增加直肠癌患者根治性手术概率,并降低复发率,改善患者的远期预后。近年来,新辅助治疗疗效的预测和评估,成为临床医生关注的焦点。在影像学方面,常规的形态成像技术,不能够准确反映新辅助放化疗后肿瘤治疗效果,而DWI-MRI、DCE-MRI、PET-CT等功能成像技术不仅能够反映肿瘤退缩程度,还可以反映治疗前后肿瘤功能代谢方面的变化,因而更为准确。现对直肠癌新辅助放化疗影像学疗效评价方法的应用现状进行综述。     

中低位进展期直肠癌患者全直肠系膜切除术前应用同步新辅助放化疗效果分析

目的：分析中低位进展期直肠癌患者全直肠系膜切除术前同步新辅助放化疗应用疗效。方法选取45例中低位进展期直肠癌患者为研究对象,将其随机分为联合组（23例）与对照组（22例）,对照组患者行单纯全直肠系膜切除术,联合组患者在行全直肠系膜切除术前同步新辅助放化疗,比较联合组新辅助放化疗前后肿瘤分期（TNM）情况,两组患者治疗前后肿瘤标志物水平变化情况及术后3个月保肛率、复发率、转移率、术后并发症发生情况。结果新辅助治疗后联合组TNM分期较治疗前降低,差异具有统计学意义（P﹤0.05）;治疗前两组患者癌胚抗原（CEA）、糖链抗原19-9（CA19-9）、糖链抗原242（CA242）水平差异无统计学意义（P﹥0.05）,治疗后均降低（P﹤0.05）,且联合组低于对照组（P﹤0.05）;两组患者术后3个月转移率及并发症发生率差异无统计学意义（P﹥0.05）,联合组保肛率高于对照组,复发率低于对照组（P﹤0.05）。结论采用全直肠系膜切除术前同步新辅助放化疗,可以有效提高中低位进展期直肠癌患者保肛率,降低复发率,改善肿瘤TNM分期,降低CEA、CA19-9、CA242水平,具有良好的应用前景。     

分子预测直肠癌新辅助放化疗后pCR的研究进展

摘 要：局部晚期直肠癌（LARC）目前的基本治疗策略是新辅助放化疗（nCRT）和随后的全直肠系膜切除术（TME）。nCRT 后的肿瘤消退在个体间差异显著,病理完全缓解（pCR）是 LARC 的预后因素。明确放化疗反应的预测因素有助于临床医生鉴别可能从多模式治疗中获益的患者,并在早期对其预后进行评估。本文结合近年的相关研究,探讨LARC在新辅助治疗后可能达到pCR的分子预测因子。     

直肠腔内彩色多普勒超声对低位局部进展期直肠癌新辅助放化疗后浸润分期的评估及其影响因素

目的：评价直肠腔内彩色多普勒超声（ERUS）对低位局部进展期直肠癌新辅助放化疗后浸润分期的评估价值及其准确性的影响因素。方法：收集2014年2月至2016年2月我院确诊的Ⅱ、Ⅲ期低位直肠癌患者38例,局部 T3/ T4期,均进行新辅助放化疗。ERUS 评价放疗前后局部病灶改变情况,与病理 T 分期比较,评价 ERUS 新辅助治疗后再分期的准确性,进行准确性影响因素的单因素分析。结果：与新辅助放化疗前比较 ERUS 显示治疗后病灶内部血流分布明显减少（P <0.05）,病灶纵轴最大长度及最大厚度降低（t =2.093, P <0.05;t =6.498,P <0.01）,uT 分期新辅助放化疗后降低（P <0.05）。与术后病理比较,ERUS 在 T1分期准确率为11.11%,T2分期准确率为28.57%,T3分期准确率为27.27%,T4分期准确率为100%。单因素分析显示,复查 ERUS 时间、术后 T 分期及 Wheeler 直肠癌消退分级是 ERUS 对低位直肠癌再分期准确性的影响因素（P =0.043;P =0.004;P =0.017）。结论：ERUS 对 T4再分期准确性较高,在辅助放化疗结束6周后复查ERUS 及消退较差的肿瘤中准确性较高,对低位直肠癌新辅助放化疗后疗效评估有应用价值。     

新辅助放化疗对局部进展期直肠癌保肛术后排便功能的影响

目的:探讨新辅助放化疗对局部进展期直肠癌保肛术后排便功能的影响。方法:回顾性分析2013年至2016年我院185例局部进展期直肠癌行直肠低位前切除术患者的临床和病理资料,采用低位前切除综合征（LARS）评分量表评估患者术后排便功能状况,通过单因素和多因素Logistic回归分析影响患者术后排便功能的危险因素。结果:所有患者均严格遵循直肠全系膜切除术（TME）原则行低位前切除术,其中113例行术前（新辅助）放化疗,50例行术后（辅助）放化疗,22例未行放化疗。术后12～48个月中,患者中LARS的发生率为64.9%,重度LARS的发生率为31.9%,重度LARS患者占全部LARS患者的49.2%。单因素分析发现,接受放化疗者术后重度LARS发生比例显著高于未接受放化疗者（P＜0.001）,肿瘤距肛缘距离＜5 cm者术后重度LARS发生比例显著高于≥5 cm者（P=0.001）,开放手术者术后重度LARS发生比例显著高于腹腔镜手术者（P=0.038）,然而放化疗的不同时机（新辅助、辅助）、新辅助放化疗的不同形式（长程放化疗、短程放疗）对术后重度LARS发生比例的影响,差异并无统计学意义（P＞0.05）。多因素分析发现,只有放化疗（P=0.001）、肿瘤距肛缘距离＜5 cm（P=0.003）是术后发生重度LARS的独立危险因素。结论:LARS是直肠癌保肛术后长期困扰患者的常见并发症,放化疗、肿瘤位置较低是导致术后LARS的独立危险因素。然而,新辅助放化疗与辅助放化疗,长程放化疗与短程放疗对术后LARS发生的影响基本相似。     

肿瘤体积对局部进展期直肠癌预后的影响

  目的  探讨肿瘤体积（gross tumor volume，GTV）对接受新辅助放化疗（neoadjuvant chemoradiotherapy，NCRT）和全直肠系膜切除术（total mesorectal excision，TME）后，局部进展期直肠癌（locally advanced rectal cancer，LARC）患者的预后影响。  方法  回顾性分析2011年1月至2016年9月湖南省肿瘤医院收治的128例初治直肠癌患者的临床资料，均接受术前同步放化疗+TME。采用受试者工作特征曲线（receiver-operating characteristic，ROC）分析GTV截点值，用Kaplan-Meier生存分析和Cox比例风险回归模型进行预后分析。  结果  行NCRT后T分期降期率为58.6%，N分期降期率为69.5%，总体降期率为77.3%，病理完全缓解（pathologi-cal complete response，pCR）率为16.4%，总体保肛率为57.03%。GTV的截点为79.31 mL，GTV ≥ 79.31 mL与GTV < 79.31 mL患者的3年总生存率（overall survival，OS）、无病生存率（disease-free survival，DFS）、无局部复发生存率（local relapse free survival，LRFS）、无远处转移生存率（distant-metastasis-free survival，DMFS）有显著性差异。GTV与MRI-T分期（ρ=0.236，P=0.007）、T分期变化（ρ=0.229，P=0.009）、TNM分期变化（ρ=0.219，P=0.013）及肿瘤退缩分级（tumor regression grade，TRG）（ρ=0.517，P < 0.001）相关，与MRI-T分期、MRI-N分期及N分期变化无关。  结论  GTV与LARC的局部复发、远处转移密切相关，是预后因素之一；肿瘤体积与治疗前T分期、新辅助治疗后的T分期变化、TNM分期变化及TRG相关，与治疗前N分期及N分期变化无关。      

局部晚期直肠癌新辅助治疗pCR相关因素研究

目的 评价局部晚期直肠癌新辅助治疗后pCR的相关影响因素。方法 回顾分析2011—2013年间收治的265例AJCC分期Ⅱ、Ⅲ期直肠癌患者资料。所有患者均接受新辅助治疗±等待手术间期化疗, 而后手术。运用单因素和二元Logistic回归多因素分析影响pCR的预测因素, 并根据预测危险因素进行归类后分为无风险组(无因素)、低风险组(1个因素)、高风险组(2个因素)。建立临床风险评估模型。因素分析运用二元Logistic回归模型。结果 达pCR者50例(18.9%)。单因素分析中新辅助治疗前CEA、放化疗前T分期、同期放化疗结束至手术间隔时间和放化疗前肿瘤最大厚度对pCR有影响(P=0.017、0.001、0.000、0.040), 多因素分析显示新辅助治疗前CEA水平和同期放化疗结束至手术间隔时间是pCR影响因素(P=0.021、0.001), 进一步分层分析表明只有非吸烟组中新辅助治疗前低水平CEA对pCR有影响(P=0.044)。临床风险评估模型诊断pCR的敏感性为80.5%, 特异性为46.0%, AUC为0.690, 阳性预测值为35.49%, 阴性预测值为86.5%, 准确性为73.9%。结论 新辅助治疗能使部分局部晚期直肠癌患者达pCR。新辅助治疗前低水平CEA和更长的同期放化疗结束至手术间隔时间是局部晚期直肠癌新辅助治疗pCR的预测因素, 而新辅助治疗前低水平CEA对pCR预测只在非吸烟人群中有效。根据新辅助治疗前CEA>5 ng/ml和同期放化疗结束至手术间隔时间≤8周的危险因素建立的临床风险评估模型可用于预测局部晚期直肠癌新辅助治疗pCR率。     

局部晚期中低位直肠癌新辅助同步放化疗58例分析

[目的]探讨局部晚期中低位直肠癌新辅助同步放化疗的疗效及其影响因素。[方法]58例局部晚期（T3-4N0-1M0）中低位直肠癌术前接受同步放化疗,放疗剂量50Gy,化疗包括奥沙利铂＋卡培他滨的联合化疗组及不含铂类药物的单药化疗组。共55例患者同步放化疗结束后2～10周内完成根治性手术,依据术后病理结果进行疗效评价。[结果]全组55例患者手术顺利,无严重手术并发症;术后病理示肿瘤完全消退8例（14．5％）,重度消退11例（20．0％）,中度消退20例（36．4％）,轻度及无消退16例（29．1％）;治疗前肿瘤（T）及淋巴结（N）临床分期与放化疗后肿瘤消退程度无关：奥沙利铂联合卡培他滨化疗组肿瘤完全消退与重度消退率为41．2％,不含铂类药物组为23．8％（P〉0．05）;与术前临床分期相比,同步放化疗后原发肿瘤（T）降期率为41．8％,淋巴结（N）降期率为58．8％。[结论]新辅助同步放化疗用于局部晚期中低位直肠癌的术前治疗可使大部分肿瘤获得不同程度消退：有关直肠癌同步放化疗疗效的预测指标以及高效的化疗方案有待进一步深入研究。     

Predictive Factors for Pathologic Complete Response Following Neoadjuvant Chemoradiotherapy for Rectal Cancer

Background: An accurate assessment of potential pathologic complete response(pCR) following neoadjuvant chemoradiotherapy(NCRT) is important for the appropriate treatment of rectal cancer. However, the factors that predict the response to neoadjuvant chemoradiotherapy have not been well defined. Therefore, this study analyzed the predictive factors on the development of pCR after neoadjuvant chemoradiation for rectal cancer. Methods: From January 2008 to January 2018, a total of 432 consecutive patients from a single institution patients who underwent a long-course neoadjuvant chemoradiotherapy were reviewed in this study. The clinicopathological features were analyzed to identify predictive factors for pathologic complete response in rectal cancer after neoadjuvant chemoradiation. Results: The rate of pathologic complete response in rectal cancer after neoadjuvant chemoradiation was 20.8%, patients were divided into the pCR and non-pCR groups. The two groups were well balanced in terms of age, gender, body mass index, ASA score, tumor stage, tumor differentiation, tumor location, surgical procedure, chemotherapy regimen and radiation dose. The multivariate analysis revealed that a pretreatment carcinoembryonic antigen (CEA) level of ≤5 ng/mL and an interval of ≥8 weeks between the completion of chemoradiation and surgical resection were independent risk factors of an increased rate of pCR. Conclusions: Pretreatment carcinoembryonic antigen (CEA) level of ≤5 ng/mL and an interval of ≥8 weeks between the completion of chemoradiation and surgical resection are predictive factors for pathologic complete response in rectal cancer after neoadjuvant chemoradiation. Using these predictive factors, we can predict the prognosis of patients and develop adaptive treatment strategies. A wait-and-see policy might be possible in highly selective cases.     

术前应用FOLFOX方案联合放疗治疗中低位直肠癌35例报告

目的探讨术前应用FOLFOX4方案化疗联合放疗治疗中低位局部进展期直肠癌的安全性和有效性。方法对本院2006年3月以来35例术前应用FOLFOX4方案联合放疗进行新辅助治疗的中低位局部进展期直肠癌患者资料进行分析。结果低位前切除术20例,腹会阴联合切除15例,保肛率为57．1％（20／35）。30例患者（85．7％）新辅助治疗后排便困难、便次增多、便血等症状得以改善。肿瘤完全消退5例,肿瘤部分缓解26例,病情稳定4例,治疗有效率为88．6％（31／35）。病理完全缓解率为14．3％;肿瘤分期降低25例,降期率为71．4％。结论FOLFOX4术前化疗方案应用于中低位局部进展期直肠癌的新辅助治疗安全有效,可达到大部分患者术前肿瘤降期。     

A2aR在直肠癌组织中的表达及其与新辅助放化疗敏感性的关系

目的:探讨A2a型腺苷受体(adenosine 2a receptor,A2aR)在直肠癌组织中的表达丰度,并探讨其与直肠癌新辅助放化疗敏感性的关系.方法:收集56例2014年06月至2019年06月期间于我院行直肠癌新辅助放化疗治疗前活检石蜡标本,采用免疫组织化学染色法检测其中A2 aR蛋白的表达情况.采用直肠癌消退...     

体素内不相干运动扩散加权成像在预测局部进展期直肠癌新辅助放化疗疗效中的初步研究

背景与目的：弥散加权成像(diffusion-weighted imaging,DWI)是目前检查活体组织中水分子扩散运动的理想方法,常规DWI使用单指数拟合函数得到表观扩散系数(apparent diffusion coefficient,ADC)值,而体素内不相干运动扩散加权磁共振成像(intravoxel incoherent motion MR imaging,IVIM-MRI)则采用足够多的低b值和高b值并使用双指数拟合函数,可获取更丰富的生物信息,因此本研究欲探讨IVIM-MRI的单、双指数模型在预测局部进展期直肠癌新辅助放化疗疗效中的应用价值。方法：纳入32例接受新辅助放化疗的局部进展期直肠癌并在新辅助治疗前、后行常规MR序列及IVIM序列扫描的患者。IVIM序列包括9个b值(0~800 s/ mm²),所得IVIM序列原始数据经单、双指数模型处理,得到单、双指数模型衰减曲线,并生成对应参数图。测量新辅助治疗前、后肿瘤实质区单指数模型ADC值和双指数模型D值、灌注系数D^*值、灌注分数f值,采用配对样本t检验进行分析;并比较病理完全缓解(pathological complete response,pCR)组和非pCR组新辅助治疗前、后参数差异。组间比较采用两独立样本t检验,P<0.05为差异有统计学意义。结果：IVIM的单指数模型中,治疗前肿瘤平均ADC值［(133.2±21.5)×10^-5 mm/s］较治疗后［(166.9±29.7)×10^-5 mm/s］小且差异有统计学意义(P<0.05);双指数模型中,新辅助放化疗前pCR组肿瘤D*值［(4 471±1 271)×10^-5 mm/ s］低于非pCR组［(5 749±1 722)×10^-5mm/s］,差异有统计学意义(P<0.05);新辅助放化疗后pCR组肿瘤D值［(97.0±14.6)×10^-5 mm/s］低于非pCR组［(113.4±22.6)×10^-5 mm/s］,且差异有统计学意义(P<0.05)。结论：基于常规DWI序列,IVIM双指数模型可更加详细补充描述肿瘤扩散信息。     

直肠癌新辅助放化疗后病理完全缓解的临床因素分析

目的 评估影响直肠癌新辅助放化疗后pCR的临床因素。方法 回顾分析2009—2012年间接受新辅助放化疗随后行根治性手术的116例直肠癌患者临床资料。所有患者术前接受盆腔调强放疗50 Gy分25次,同期氟尿嘧啶为基础化疗,完成治疗休息4~8周后行根治性手术。应用 Logistic法分析影响pCR和非pCR的临床因素。结果 共20例患者经新辅助放化疗后达pCR,pCR率为17.2%。单因素分析表明肿瘤侵犯直肠管腔周径范围达75%以上(全周肿瘤)、治疗前血清CEA水平、T分期、N分期、肛缘距离、分化程度、肿瘤最大直径与直肠癌新辅助放化疗后肿瘤pCR水平相关。多因素分析结果显示全周肿瘤、治疗前血清CEA水平和T分期是影响放化疗后肿瘤pCR预测因素。结论 非全周肿瘤、低CEA水平和早T分期等治疗前临床因素可能是获得pCR的重要决定因素。     

Prognostic and predictive value of baseline and posttreatment molecular marker expression in locally advanced rectal cancer treated with neoadjuvant chemoradiotherapy

PURPOSE: To evaluate expression of a panel of molecular markers, including p53, p21, MLH1, MSH2, MIB-1, thymidylate synthase, epidermal growth factor receptor (EGFR), and tissue vascular endothelial growth factor (VEGF), before and after treatment in patients treated with neoadjuvant chemoradiotherapy for locally advanced rectal cancer, to correlate the constitutive profile and dynamics of expression with pathologic response and outcome. METHODS AND MATERIALS: Expression of biomarkers was evaluated by immunohistochemistry in tumor samples from 91 patients with clinical Stage II and III rectal cancer treated with preoperative pelvic radiotherapy (50 Gy) plus concurrent 5-fluorouracil by continuous intravenous infusion. RESULTS: A pathologic complete remission was observed in 14 patients (15.4%). Patients with MLH1-positive tumors had a higher pathologic complete response rate (24.3% vs. 9.4%; p = 0.055). Low expression of constitutive p21, absence of EGFR expression after chemoradiotherapy, and high Dworak's tumor regression grade (TRG) were significantly associated with improved disease-free survival and overall survival. A high MIB-1 value after chemoradiotherapy was significantly associated with worse overall survival. Multivariate analysis confirmed the prognostic value of constitutive p21 expression as well as EGFR expression and MIB-1 value after chemoradiotherapy among patients not achieving TRG 3-4. CONCLUSIONS: In our study, we observed the independent prognostic value of EGFR expression after chemoradiotherapy on disease-free survival. Moreover, our study suggests that a constitutive high p21 expression and a high MIB-1 value after neoadjuvant chemoradiotherapy treatment could predict worse outcome in locally advanced rectal cancer.     

Gene Expression Profiles of Epidermal Growth Factor Receptor,Vascular Endothelial Growth Factor and Hypoxia-inducible Factor-1 with Special Reference to Local Responsiveness to Neoadjuvant Chemoradiotherapy and Disease Recurrence After Rectal Cancer Surgery

AimsTo establish a causal relationship between the gene expression profiles of angiogenetic molecular markers, including epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF) and hypoxia-inducible factor-1 (HIF-1), in rectal cancer and the local responsiveness to neoadjuvant chemoradiotherapy and subsequent disease recurrence.Materials and methodsWe examined the pre-treatment tumour biopsies (n = 40) obtained from patients with rectal adenocarcinoma (clinical International Union Against Cancer stage ll/III) who were scheduled to receive neoadjuvant 5-fluorouracil-based chemoradiotherapy for EGFR, VEGF and HIF-1 expression by quantitative real-time polymerase chain reaction.ResultsResponders (patients with significant tumour regression, i.e. pathological grades 2/3) showed significantly lower VEGF, HIF-1 and EGFR gene expression levels than the non-responders (patients with insignificant tumour regression, i.e. pathological grades 0/1) in the pre-treatment tumour biopsies. The elevated expression level of each gene could predict patients with a low response to chemoradiation. During the median follow-up of all patients (41 months; 95% confidence interval 28–60 months), 6/40 (15%) developed disease recurrence. Although local responsiveness to neoadjuvant chemoradiotherapy was associated with neither local nor systemic disease recurrence, lymph node metastasis and an elevated VEGF gene expression level were independent predictors of systemic disease recurrence. The 3-year disease-free survival rates of the patients with lower VEGF or EGFR expression levels were significantly lower than those of patients with higher VEGF or EGFR expression levels.ConclusionsAnalysing VEGF expression levels in rectal cancer may be of benefit in estimating the effects of neoadjuvant chemoradiotherapy and in predicting systemic recurrence after rectal cancer surgery.     

Tumor infiltrating lymphocytes (TILs) before and after neoadjuvant chemoradiotherapy and its clinical utility for rectal cancer

Backgrounds: Radiotherapy (RT) and chemotherapy (CT) can potentiate systemic antitumor immune effect. However, immunomodulation during RT or CT and their clinical implications in rectal cancer have not been thoroughly investigated. Methods: We investigated alterations in the densities of tumor infiltrating lymphocytes (TILs) during chemoradiation and their clinical utilities in patients with rectal cancer. We analyzed 136 rectal cancer patients who underwent neoadjuvant RT, CT or chemoradiotherapy (CRT), followed by radical resection retrospectively. Pretreatment biopsy specimens and posttreatment resected specimens of all patients were immunostained for CD3 and CD8. The predictive value of TILs to neoadjuvant treatment and prognosis were examined. Results: Densities of CD3+ and CD8+TILs in posttreatment specimens after RT, CT or CRT were all significantly higher than those in pretreatment specimens. There were no significant differences between each two of these three groups. High pretreatment CD3+ and CD8+TILs were associated with good response (TRG ≥ 3) after neoadjuvant treatments (P = 0.033 and 0.021). High CD3+TILs and CD8+TILs in pretreatment biopsy specimens were significantly associated with favorable disease free survival (DFS) (P = 0.010 and P = 0.022) and overall survival (OS) (P = 0.019 and P = 0.003). Conclusions: We may, thus, conclude that chemoradiation can enhance local immune response by increased TILs. High TILs densities before treatment are associated with good response to neoadjuvant chemoradiotherapy and a favorable prognosis.     

Tumor regression in mesorectal lymphnodes after neoadjuvant chemoradiation for rectal cancer.

AIMS: The histological modification produced by neoadjuvant chemoradiation on primary rectal cancer has been investigated by many authors, and a prognostic value of tumor regression grade (TRG) has been identified. Tumor regression grade on metastatic mesorectal lymphnodes has been never evaluated. The purpose of this study is to analyse the TRG on mesorectal lymphnodes (lymphnode regression grade, LRG) after preoperative chemoradiation in rectal cancer patients and to determine the correlation with TRG of primary tumor. METHODS: Surgical specimens from 35 patients who underwent chemoradiation were included. LRG on mesorectal lymphnodes was assessed by immunohistochemistry. Response to treatment was evaluated by a 5-point LRG based on the ratio of residual tumor to fibrosis. RESULTS: Complete pathologic response (LRG 1) was observed in 18 patients (51%). In 4 patients (11%) no regression was observed (LRG 5). In 4 cases only reactive lymphnodes were found. LRG on lymphnodes significantly correlated with TRG on primary tumor (p<0.05). CONCLUSIONS: Neoadjuvant chemoradiation determines a tumor regression on mesorectal lymphnodes as on primary tumor; further studies are needed to evaluate the prognostic value of LRG.     

LGR5, HES1 and ATOH1 in Young Rectal Cancer Patients in Egyptian

Objective: The study aimed to delineate the gene expression profile of LGR5, HES1 and ATOH1 in young Egyptian rectal cancer (RC) patients and investigate the correlation between expression profiles and clinical outcome. Methods: The study was conducted on 30 young Egyptian RC patients. Expression study of LGR5, HES1 and ATOH1 were performed by quantitative PCR (QPCR) based on comparative Cq method after normalization to adjacent non tumor tissues and ACTB as a reference gene. Patients were followed up for assessment of response to neoadjuvant chemoradiotherapy (CRT) based on revised RECIST1.1. Result: The study detected overexpression of LGR5 and HES1 and down-regulation of ATOH1 in human RC tissues compared to non- tumor tissues. High expression of LGR5 was correlated with more depth of tumor invasion, lymph node (LN) metastasis, advanced cTNM stage and mesorectal fascia (MRF) involvement. More prominently, high LGR5 expression level was associated with poor response to CRT. LGR5 was suggested as unfavorable prognostic biomarker for RC. Conversely, HES1 and ATOH1 expression did not show significant association with most of the studied clinical criteria nor response to CRT. Still, HES1 and ATOH1 were significantly and inversely associated with presence of mucinous component. Conclusion: High LGR5 expression is indicative of poor prognosis among young Egyptian RC patients and is proposed as a predictive marker of resistance to neoadjuvant CRT. However, HES1 and ATOH1 expressions were not prognostic nor predictive of response to CRT. Overall, LGR5, HES1 and ATOH1 gene expression patterns among young onset RC patients, are in line with patterns encountered in older age groups.