肿瘤退缩分级标准的对比及其在直肠癌诊治中的应用进展

随着新辅助治疗在直肠癌中的规范化推广,肿瘤退缩分级（TRG）标准逐渐引起广泛关注和重视。多项研究证实TRG与直肠癌患者新辅助治疗反应、生存预后有一定相关性,在患者生存预测、随访和临床诊疗策略等方面均有应用前景,甚至也有报道考虑将其纳入临床试验替代终点。但是目前TRG标准各异,尚未统一化、规范化,故本文旨在对目前常见TRG标准进行汇总对比,并进一步探讨其在直肠癌诊治中的临床应用。     

直肠癌新辅助放化疗研究问题探讨

新辅助放化疗已成为局部进展期直肠癌的标准治疗模式,如何在这个模式下选择适合放化疗的患者,评估治疗价值以及对术后病理指导治疗模式的改变,都是目前研究的热点。     

直肠癌新辅助放化疗的探索

对于局部晚期直肠癌,美国NCCN指南或欧洲ESMO指南均推荐术前放疗或放化疗联合全直肠系膜切除术（total mesorectal excision,TME）作为标准的治疗模式,使局部晚期直肠癌的治疗疗效取得了显著提高。为进一步降低远处转移率、提高生存率,目前对多种新辅助治疗的模式展开了探索,并取得初步成效。     

MRI在直肠癌新辅助治疗疗效评估中的价值

直肠癌新辅助放化疗可使肿瘤出现不同程度的消退,部分病灶甚至可以达到病理完全缓解,从而提高外科手术切除率,降低局部复发率。对肿瘤新辅助治疗疗效的准确评估,是选择个体化治疗方案的关键。磁共振成像对于直肠癌术前分期的价值得到广泛认可,其在新辅助治疗疗效评估中的作用仍在持续研究中。肿瘤体积测量是传统的应用评价指标,但繁琐的测量与计算过程一定程度上限制了其临床应用。多种功能成像序列的发展,为新辅助放化疗后疗效评估提供了更多更有效的选择方式。尽管如此,MRI对于分辨极少量残存的肿瘤细胞仍具有一定的困难,尤其是对于治疗后肿瘤完全缓解的评价,尚有待进一步研究与探索。     

中期和局部晚期老年直肠癌辅助放化疗进展

直肠癌是我国及世界范围内最常见的肿瘤之一,其中的高龄患者比例逐年增加。由于缺乏针对高龄患者的前瞻性循证医学证据,目前高龄患者综合治疗的标准方案尚待明确,相当比例的高龄患者并未得到最佳的综合治疗。本文将主要从老年直肠癌的流行病学、治疗模式,尤其是（新）辅助放化疗方面,系统回顾现有资料,探讨中期及局部晚期老年直肠癌的最佳治疗模式。     

预测局部晚期直肠癌新辅助放化疗疗效潜在的生物标记物

新辅助放化疗联合手术的治疗模式已成为局部晚期直肠癌（locally advanced rectal cancer,LARC）的标准治疗方案,准确预测新辅助放化疗后直肠肿瘤消退,特别是病理性完全缓解具有十分重要的意义,有助于为患者制定个体化治疗方案。因此,我们对可用于预测局部晚期直肠癌患者新辅助放化疗疗效的评价指标进行了综述和分析,并展望直肠癌放化疗疗效预测的进一步研究。     

进展期直肠癌新辅助放化疗研究进展

我国结直肠癌发病率和死亡率居高不下,直肠癌的发病率与术后局部复发率(LRR)通常高于结肠癌,且手术难度高。目前为了防止直肠癌的局部复发大多采取多学科方法医治。新辅助放化疗(nCRT)作为一种发展中的多学科方法,可提高治愈率又可维持器官功能,在直肠癌治疗中起着至关重要的作用。本综述旨在阐明nCRT的现状与未来的改进方向。     

局部进展期直肠癌新辅助放化疗后病理完全缓解临床相关因素探究

目的探讨局部进展期直肠癌新辅助放化疗后病理完全缓解（pCR）的临床相关因素。 方法回顾性分析2013年1月至2018年5月期间四川省肿瘤医院肠道外科病区收治的117例局部进展期直肠癌新辅助放化疗及手术的临床资料,采用单因素分析及logistic二分类多因素回归分析法研究pCR的临床相关因素。 结果117例患者全部完成新辅助放化疗及根治手术,其中19例（16.24%）患者达到pCR。单因素分析结果显示,性别为女性（P=0.024）,年龄较年轻（P=0.042）,放疗前CEA<5 ug/L（P=0.015）,无吸烟史（P=0.008）,无饮酒史（P=0.037）,肿瘤距肛缘距离大于6 cm（P=0.048）和局部进展期直肠癌新辅助放化疗后高pCR率有关。多因素回归分析结果显示,放疗前CEA<5 ug/L（P=0.039）和肿瘤距肛缘距离>6 cm（P=0.043）是影响局部进展期直肠癌新辅助放化疗后pCR率的独立因素。 结论放疗前CEA水平和肿瘤距肛缘距离是影响局部进展期直肠癌新辅助放化疗后pCR率的相关临床因素。     

局部晚期直肠癌新辅助化疗的机遇

结直肠癌是最常见的消化道恶性肿瘤之一。在我国,结直肠癌的发病率呈逐年上升趋势,且我国直肠癌占结直肠癌的比例仍然明显高于欧美国家。术前或术后的同步放化疗已被证实可显著降低直肠癌的局部复发率,是目前局部晚期直肠癌围手术期的标准治疗模式。近年来,直肠癌新辅助化疗的作用越来越受到重视,本文就目前局部晚期直肠癌新辅助治疗存在的问题和以新辅助化疗为主的新治疗理念的研究现状进行阐述。     

Predicting tumor response after preoperative chemoradiation using clinical parameters in rectal cancer

AIM: To evaluate the clinical parameters and identify a better method of predicting pathological complete response (pCR). METHODS: We enrolled 249 patients from a database of 544 consecutive rectal cancer patients who underwent surgical resection after preoperative chemoradiation therapy (PCRT). A retrospective review of morphological characteristics was then performed to collect data regarding rectal examination findings. A scoring model to predict pCR was then created. To validate the ability of the scori...     

直肠癌放疗的标准流程

因特异性症状的缺乏,大多数直肠癌患者就诊时已处于晚期或局部晚期。对于局部晚期直肠癌（II/III期）患者,放射治疗联合根治性的全直肠系膜切除TME手术能显著的提高患者的局部控制率并延长总的生存时间。目前,调强放射治疗技术已广泛开展。然而,各医疗中心在直肠癌放疗实施过程,治疗流程中存在显著差异。本文现对我院直肠癌的放疗标准流程做一简单介绍以供参考。     

中低位直肠癌的诊治策略

我国中低位直肠癌发病率较高,近年来,尤其以局部切除为主的手术治疗方式研究进展较快。笔者以术前分期为依据,对当前国内外中低位直肠癌治疗进展予以综述。     

直肠癌术前新辅助放疗进展

术前同步放化疗是局部进展期可切除直肠癌的标准治疗。取得了与术后同步放化疗相似的生存率,并进一步降低了局部复发率,同时提高了保肛率。通过术前同步放化疗达到病理完全缓解的患者有更好的预后。本文将介绍直肠癌术前放疗的进展。     

Instrumental clinical restaging,pathological evaluation,and tumor regression grading: how to assess the response to neoadjuvant chemoradiotherapy for rectal cancer

Introduction The object of neoadjuvant chemoradiotherapy regimens is a downstaging or downsizing of advanced rectal tumor to increase the rate of curative resection and reduce loco-regional failure. A reliable method of assessing response to adjuvant therapies is required to help standardize the assessments of new multimodality therapies. The purpose of this study was to evaluate the role played by tumor regression grading on the evaluation of pathological response to chemoradiotherapy, compared with both the predicting value of the clinical response to neoadjuvant therapy and pathologic response evaluation.Methods From 1994 to 2003, 58 patients with a primary diagnosis of rectal cancer were studied at our department and enrolled in a single center, not randomized study based on 5-week sessions of radiotherapy associated with a 30-day 5-fluorouracil (FU) infusion, followed by surgical resection. Instrumental restaging and routine histological examination, including tumor regression grading, were performed to asses the response to neoadjuvant therapy.Results The cCR rate corresponds to pCR rate, while a 3.5% of cPR and a 3.4% of cSD corresponded to a pPD. cPR and cSD show a PPV of 92.8% and 90.9% respectively, while cPD NPV is 20%. No case was found with no regression (grade 0). Tumor regression was defined grade 1 in 24.5% of cases, grade 2 was found in 58.5% of cases, 7.5% were grade 3, and 9.5% showed complete regression (grade 4). Pathologic response resulted to be associated with regression grade (p=0.006). Tumor regression grading is an independent variable for pT (p=0.0002), pN status (p=0.00004), pathologic staging (p=0.000001) and local recurrence (p=0.003).Conclusion Our results lead us to consider only pathologic evaluation to determine the response to neoadjuvant treatment: the application of tumor regression grading on the specimens obtained after combined neoadjuvant chemoradiotherapy and surgery is useful to plan a better therapeutic strategy on the ground of a quantitative evaluation of the response to neoadjuvant treatment; it shows it is an important comparable pathological feature, useful in comparing different protocols’ results and differences between patient’s response as well as prognostic factors.     

直肠癌术前放疗进展

2004年德国CAO/ARO/AIO-94临床研究奠定了局部晚期直肠癌术前新辅助放化的治疗策略。近年来,全世界对于如何进一步提高放化疗疗效和个体化治疗在放疗同期药物配比、新辅助放化疗前加入诱导化疗、延长新辅助放化疗至手术间隔期、放化疗后器官保留和中国患者适应性等五方面进行了探索,本文将对上述方面进行阐述。     

Morphological observation of tumor infiltrating immunocytes in human rectal cancer

AIM: To investigate the morphological characterization of tumor infiltrating dendritic cells (TIDCs) and tumor infiltrating lymphocytes (TILs) in human rectal cancer. METHODS: Light and electron microscopy as well as im-munohistochemistry were used to observe the distributive and morphological changes of TIDCs and TILs. RESULTS: TIDCs were mainly located in tumor-surrounding tissue. The number of TIDCs in the earlier stage was higher than that in the later stage (P<0.01). TILs were mainly seen in adjacent tissue of cancers and tumor-surrounding tissue. There were more TILs in the earlier stage than that in the later stage (P<0.01). Under electron microscope, TIDCs were irregular in shape and exhibited many dendritic protrusions. It isn't obvious that cancer cells perforated the basement membrane and TILs were arranged along the basement membrane in the earlier stage. In the later stage, it is explicit that cancer cells perforated the basement membrane and surrounded by TILs. There were contacts among TIDCs, TILs and tumor cell. One TIDCs contacted one or several TILs which clustered around TIDCs. Glycogen granules were seen between TIDCs and TILs. CONCLUSION: The number of TIDCs and TILs is related with tumor progression There exist close relationships among TIDCs, TILs and tumor cell.     

Tumor regression grades:Potential outcome predictor of locally advanced rectal adenocarcinoma after preoperative radiotherapy

AIM:To analyze tumor regression grade(TRG)for prognosis of locally advanced rectal adenocarcinoma(LARA)treated with preoperative radiotherapy.METHODS:One hundred and ninety patients with clinical stageⅡ/ⅢLARA were studied.All patients underwent radical surgery(between 2004 and 2010)after 30-Gy/10-fraction preoperative radiotherapy(preRT).All 190 patients received a short course of preRT and were reassessed for disease recurrence and survival;the slides of surgical specimens were reviewed and classified according to Mandard TRG.We compared patients with good response(Mandard TRG1 or TRG2)vs patients with bad/poor response(Mandard TRG3-5).Outcomes evaluated were 5-year overall survival(OS),5-year disease-free survival(DFS),and local,distant and mixed recurrence.Fisher’s exact test orχ2 test,logrank test and proportional hazards regression analysis were used to calculate the probability that Mandard TRG was associated with patient outcomes.RESULTS:One hundred and sixty-six of 190 patients(87.4%)were identified as Mandard bad responders(TRG3-5).High Mandard grade was correlated with tumor height(41.7%6 cm vs 58.3%≥6 cm,P=0.050),yp T stage(75%yp T0-2 vs 25%yp T3-4,P=0.000),and yp N stage(75%yp N0 vs 25%yp N1,P=0.031).In univariate survival analysis,Mandard grade bad responders had significantly worse OS and DFSthan good responders(TRG1/2)(OS,83.1%vs 96.4%,P=0.000;DFS,72.3%vs 92.0%,P=0.002).In multivariate survival analysis,Mandard bad responders had significantly worse DFS than Mandard good responders(DFS 3.8 years(95%CI:1.2-12.2 years,P=0.026).CONCLUSION:Mandard grade good responders had a favorable prognosis.TRG may be a potential predictor for DFS in LARA after pre-RT.