腹腔镜与传统手术联合新辅助放化疗治疗直肠癌的疗效分析

目的比较腹腔镜与传统手术联合新辅助放化疗治疗直肠癌的临床疗效。方法选取2011年6月至2013年6月间治疗的56例直肠癌患者,随机分为腹腔镜手术组和传统手术组,所有患者术前均行新辅助放化疗,新辅助放化疗结束6~8周后,行直肠癌根治术。结果两组患者的手术方式、淋巴结清扫数目及并发症、复发情况等方面差异无统计学意义(P>0.05)。腹腔镜手术组术中出血量、术后恢复时间、住院时间均显著短于传统手术组(P<0.05),手术时间长于传统手术组(P<0.05)。结论腹腔镜联合新辅助放化疗治疗直肠癌与传统手术相比并未增加手术风险,且有同样的疗效,安全可行,可临床推广应用。     

腹腔镜和开腹手术联合同步新辅助放化疗治疗进展期直肠癌的近期疗效比较

目的比较腹腔镜和开腹手术联合同步新辅助放化疗治疗进展期直肠癌的近期疗效。方法将136例进展期直肠癌患者行同步新辅助放化疗,对可接受手术的128例随机分为腹腔镜手术组（62例）和开腹手术组（66例）,比较两组患者的术中情况,手术方式,术后恢复情况,近期并发症发生率及术后住院时间。结果两组患者在术中出血量,术后排气排便时间,进食时间及术后住院时间差异均有统计学意义（均P〈0．05）;手术方式及术后近期总并发症发生率则无显著差别。结论进展期直肠癌术前行同步放化疗后,腹腔镜手术优于开腹手术,安全有效。     

局部进展期直肠癌新辅助放化疗的研究进展

术前放化疗联合全系膜切除手术为局部晚期直肠癌患者治疗的标准模式,术前放化疗比术后放化疗提高了肿瘤降期率、保肛率及局部控制率,术前放化疗后达到病理完全缓解患者拥有更好的预后。本文就近年来术前放化疗的研究进展作一综述。     

局部进展期直肠癌新辅助放化疗的研究进展

术前放化疗联合全系膜切除手术为局部晚期直肠癌患者治疗的标准模式,术前放化疗比术后放化疗提高了肿瘤降期率、保肛率及局部控制率,术前放化疗后达到病理完全缓解患者拥有更好的预后。本文就近年来术前放化疗的研究进展作一综述。     

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。     

同步新辅助放化疗联合全直肠系膜切除术治疗中低位局部进展期直肠癌的临床研究

目的:探讨同步新辅助放化疗联合全直肠系膜切除术(total mesorectal excision,TME)治疗中低位局部进展期直肠癌的疗效及安全性。方法:2009年9月-2011年2月30例中低位局部进展期直肠癌患者[Ⅱ期(T3-4N0M0)14例,Ⅲ期(T1-4N1-2M0)16例]接受了术前同步新辅助放化疗(术前放疗总剂量为45～50Gy,1.8Gy/次;化疗方案为FOLFOX4,化疗2个周期)。同步新辅助放化疗结束后4～6周行手术治疗,遵循TME原则。结果:全部患者均完成同步新辅助放化疗,CR5例、PR18例、SD7例,有23例(76.7%)患者的临床TNM分期下降。同步新辅助放化疗结束后4～6周,除1例CR患者拒绝手术外,29例患者均行手术治疗,其中23例行低位或超低位前切除术(Dixon术),6例行腹会阴联合切除术(Miles术),保肛率为80.0%(24/30)。无一例发生围手术期死亡,术后并发症的总发生率为20.7%(6/29)。结论:同步新辅助放化疗联合TME治疗中低位局部进展期直肠癌安全而有效,可以降低肿瘤分期、提高肿瘤切除率和保肛率,改善患者的生活质量。     

局部进展期直肠癌新辅助放化疗后缓解率的准确性评估

新辅助放化疗是局部进展期直肠癌术前的首选辅助治疗,其使肿瘤降期、降级的作用已得到广泛认可.部分局部进展期直肠癌患者经新辅助放化疗后可达到临床完全缓解(cCR),经术后病理证实为病理完全缓解(pCR).而准确评估缓解率对制定局部进展期直肠癌的后续治疗策略有重要指导作用,本文主要对局部进展期直肠癌缓解率的准确性评估予以综述.     

局部进展期直肠癌术前新辅助放化疗中VMAT的可行性研究

目的 探讨VMAT在局部进展期直肠癌(LARC)新辅助放化疗(NCR)中的可行性。方法 回顾分析2011—2013年本院行术前NCRT+手术±术后化疗的162例LARC患者,男113例、女49例,年龄23~84岁(中位数56岁)。临床分期为Ⅱ_a、Ⅱ_b、Ⅱ_c期分别为22、11、5例,Ⅲ_a、Ⅲ_b、Ⅲ_c期分别为1、58、65例。放疗均使用了单弧VMAT,PTV₁ 50 Gy分25次,PTV₂ 46 Gy分25次。主要化疗方案为Xelox方案(卡培他滨1000 mg/m²+奥沙利铂100 mg/m²或130 mg/m²),均接受诱导及同期化疗(中位数3程)。结果 所有患者均完成放疗计划,仅2例因3级腹泻中断放疗。放化疗期间全组累计3级血液学及非血液学不良反应发生率分别为9.3%与16.0%。患者距放疗结束后34~86 d (中位数53.5 d)手术,术后pCR率30.2%,R₀切除率100%,低位直肠癌保肛率45.9%。术后不良反应累计发生率16.7%,术后30 d内无死亡病例。T、N期及临床分期降期率分别为85.2%、87.1%及88.9%。结论 VMAT用于LARC术前放化疗安全可行,但对长期生存影响尚需进一步观察。     

局部进展期低位直肠癌新辅助放化疗初步临床观察

目的 探讨局部进展期低位直肠癌新辅助放化疗疗效。方法 回顾分析2014-2018年间入组的46例局部进展期低位直肠癌患者,肿瘤下缘距肛缘6cm内。术前放疗采用SIB-IMRT技术,直肠肿瘤及阳性淋巴结照射58.75Gy分25次(2.35 Gy/次),盆腔淋巴引流区照射50Gy分25次(2.0 Gy/次),同步口服卡培他滨进行化疗。放化疗结束后间隔6~12周行直肠癌根治术。Kaplan-Meier法计算总生存(OS)、无瘤生存(DFS)、无进展生存(PFS),无局部复发生存(LRFS)、无转移生存(MFS)。单因素分析用log-rank法检验,多因素分析用Cox回归模型。结果 中位随访时间为47个月,局部复发3例,远处转移6例,ypCR率为26%(12/46),保肛手术率为74%(34/46),R0切除率为100%(44/44),TN总降期率为87%(40/46),术后并发症发生率为13%(6/46)。3年OS、DFS、PFS分别为93%、91%、87%。单因素分析显示ypN分期是影响OS、DFS、PFS、LRFS、MFS的重要因素(均P<0.05),多因素分析显示ypN分期与DFS、PFS、LRFS、MFS均显著相关(均P<0.05)。 结论 局部进展期低位直肠癌患者行术前SIB-IMRT 58.75 Gy分25次联合卡培他滨化疗方案安全可行,提高了ypCR率及生活质量,不良反应可耐受,长期生存是否获益有待进一步深入研究。     

局部进展期直肠癌新辅助放化疗疗效评价

新辅助放化疗自应用于临床以来已取得了令人鼓舞的治疗效果。其目的是通过术前放疗和化疗不同程度的减轻肿瘤负荷,使肿瘤缩小,降低临床分期,提高手术的切除率和根治率,并降低局部复发率。本文总结了近年来局部进展期直肠癌新辅助放化疗疗效评价方面的研究进展,为新辅助治疗应用模式的个体化选择提供了新思路。     

局部晚期直肠癌新辅助放化疗联合免疫治疗的研究进展

对于局部晚期(T3-4/N+M0)直肠癌, 新辅助放化疗联合全直肠系膜切除术的标准治疗模式可以明显减少局部复发、增加肿瘤退缩, 但是远处转移没有得到改善。放疗和免疫治疗相辅相成, 两者联合具有良好的理论基础。近年来, 局部晚期直肠癌新辅助放化疗联合免疫治疗的相关临床试验逐渐展开, 在微卫星不稳定(MSI-H)和微卫星稳定(MSS)患者中均进一步提高肿瘤退缩程度和病理性完全缓解率, 增加器官保留概率, 为"等待观察"策略提供更多可能。新辅助放化疗联合免疫治疗未来仍需要更多的大型临床试验进行验证, 期待能带来更好的生存获益。     

Defining and predicting early recurrence in patients with locally advanced rectal cancer treated with neoadjuvant chemoradiotherapy

BackgroundThe definition of “early recurrence (ER)” after rectal cancer surgery is currently unclear.ObjectiveTo determine an evidence-based cut-off to distinguish early and late recurrence (LR) for patients with rectal cancer and compare the clinicopathological factors between the two groups.MethodsPatients who underwent neoadjuvant chemoradiotherapy (nCRT) and radical resection for locally advanced rectal cancer were included. A minimum p-value approach was used to evaluate the optimal cut-off value of recurrence-free survival to divide the patients into ER and LR groups based on overall survival. A logistic regression model was used to assess risk factors for ER.ResultsA total of 763 patients were included, of which 167 (21.9%) experienced recurrence. The optimal cut-off value of recurrence-free survival to differentiate between ER (n = 125, 74.9%) and LR (n = 42, 25.1%) was 24 months (P = 0.000001). The median postrecurrence survival of ER and LR was 12 months and 22 months, respectively (p = 0.028). The most common recurrent sites in patients with ER and LR were lung metastases, the incidence of liver metastases, however, differed considerably in ER and LR (27.2% vs 9.5%, P = 0.019). Risk factors including elevated preoperative carcinoembryonic antigen (CEA), higher ypTNM stage, positive circumferential resection margin (CRM), and perineural invasion were significantly associated with ER.ConclusionA recurrence-free interval of 24 months is the optimal cut-off value for defining ER versus LR. Elevated preoperative CEA, higher ypTNM staging, positive CRM, and perineural invasion were associated with ER of locally advanced rectal cancer.     

靶向治疗联合新辅助放化疗在局部进展期直肠癌中的应用

目前新辅助放化疗联合全直肠系膜切除术（TME）是局部进展期直肠癌（LARC）的标准治疗模式.靶向药物在LARC新辅助治疗中耐受性及安全性良好,但与常规新辅助放化疗相比较,病理完全缓解（pCR）率并无提高,仍需大样本随机对照研究证实其在LARC新辅助治疗中的作用.     

Individualized conditional survival nomograms for patients with locally advanced rectal cancer treated with neoadjuvant chemoradiotherapy and radical surgery

BackgroundConditional survival (CS) considers the time already survived after surgery when estimating the survival probability, which may provide further useful prognostic information.ObjectiveTo evaluate CS in patients with locally advanced rectal cancer (LARC) treated with neoadjuvant chemoradiotherapy (nCRT) and to create CS nomograms predicting the conditional probability of survival after proctectomy.MethodsConsecutive patients with LARC who received nCRT followed by radical resection between 2011 and 2016 were identified. CS was defined as the probability of surviving y years after already surviving for x years. The formula used for CS was CS(x|y) = S(x + y)/S(x), where S(x) represents the survival at x years. Nomograms were constructed to predict the 5-year conditional overall survival (cOS) and conditional recurrence-free survival (cRFS).ResultsA total of 785 patients were included. The median follow-up time was 65.5 months. The probability of achieving 5-year survival after surgery for cancer increases with additional survival time. Maximum tumor diameter, distance from the anal verge, preoperative CA19-9 level, ypTNM stage and perineural invasion were independent predictors of OS, while maximum tumor diameter, distance from the anal verge, ypTNM stage and perineural invasion were independent risk factors for RFS. The nomograms predicted 5-year cOS and cRFS using these predictors and the time already survived. The online calculator can be accessed at http://www.rectalcancer.top/webcalculator.ConclusionThe proposed nomograms predict survival in patients after surgery, taking the time already survived into account.     

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.     

A phase II study of neoadjuvant chemoradiotherapy with oxaliplatin and capecitabine for rectal cancer

Purpose

This study evaluated the efficacy and safety of neoadjuvant chemoradiotherapy with the XELOX regimen in rectal cancer patients.

Patients and methods

Twenty-five patients with histopathologically confirmed and locally advanced rectal cancer (T3/T4 or N+) were enrolled in the study. Radiotherapy of 5000 cGy was delivered in 25 fractions of 200 cGy five times per week for a total of 5 weeks. During the first, second, fourth and fifth weeks of radiotherapy, the patients also received the following chemotherapy: 50 mg/m² oxaliplatin on day one and 850 mg/m² capecitabine bid for 5 days. Surgery was scheduled 5–6 weeks after the completion of the preoperative chemoradiotherapy. Four weeks after the surgery, four more cycles of chemotherapy were administered every 3 weeks. The postoperative chemotherapy consisted of 130 mg/m² oxaliplatin on day 1 and 1000 mg/m² capecitabine bid from day 1 to day 14. The end points were the downstage rate, R0 resection rate, and sphincter preservation rate.

Results

Twenty-five patients received the neoadjuvant chemoradiotherapy. The overall regression rate was 85%, with a Grade 3/4 regression rate of 30% and a pathological complete response rate of 12%. Among the 17 patients with lower rectal cancer, thirteen (76%) were originally indicated for abdominal–perineal resection (APR). However, after the neoadjuvant chemoradiotherapy, the anus could be preserved in nine patients (53%). The most frequent toxicities of the chemoradiotherapy were diarrhea (64%) and hematological toxicity (60%), followed by nausea and vomiting (48%), urinary tract irritation (28%), and anal pain (24%). Grade 3 or 4 adverse events were relatively infrequent and presented as diarrhea (12%), myelosuppression (8%), and elevated transaminase (4%). Six cases also experienced long-term anal exudates after surgery.

Conclusions

Neoadjuvant chemoradiotherapy using the XELOX regimen in rectal cancer patients obviously reduced the TNM staging and improved the pathological complete response rate. The therapy was well-tolerated and had mild adverse events and no serious perioperational complications.     

Predictive factors for early distant metastasis after neoadjuvant chemoradiotherapy in locally advanced rectal cancer

BACKGROUNDDistant relapse is the leading cause of cancer-related death in locally advanced rectal cancer. Neoadjuvant chemoradiation (NACRT) followed by surgery inevitably delays delivery of systemic treatment. Some patients show early distant metastasis before systemic treatment.AIMTo identify the most effective treatments. We investigated prognostic factors for distant metastasis, especially early distant metastasis, using the standard treatment paradigm to identify the most effective treatments according to recurrence risk.METHODSFrom January 2015 through December 2019, rectal cancer patients who underwent NACRT for having clinical T 3-4 or clinical N 1-2 disease according to the 8^th American Joint Committee on Cancer staging system were included. Radiotherapy was delivered to the whole pelvis with concomitant chemotherapy. Patients received surgery 6-8 wk after completion of NACRT. Adjuvant chemotherapy was administered at the physician’s discretion. RESULTSA total of 127 patients received NACRT. Ninety-three patients (73.2%) underwent surgery. The R0 resection rate was 89.2% in all patients. Pathologic tumor and node downstaging rates were 41.9% and 76.3%. Half the patients (n = 69) received adjuvant chemotherapy after surgery. The 3-year distant metastasis-free survival (DMFS) and overall survival (OS) rates were 81.7% and 83.5%. On univariate analyses, poorly differentiated tumors, > 5 cm, involvement of mesorectal fascia (MRF), or presence of extramural involvement (EMVI) were associated with worse DMFS and OS. Five patients showed distant metastasis at their first evaluation after NACRT. Patients with early distant metastasis were more likely to have poorly differentiated tumor (P = 0.025), tumors with involved MRF (P = 0.002), and EMVI (P = 0.012) than those who did not. CONCLUSIONEMVI, the involvement of MRF, and poor histologic grade were associated with early distant metastasis. In order to control distant metastasis and improve treatment outcome, selective use of neoadjuvant treatment according to individualized risk factors is necessary. Future studies are required to determine effective treatment strategies for patients at high risk for distant metastasis.     

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。     

局部进展期中低位直肠癌新辅助放化疗临床疗效及预后影响因素分析

目的 探讨新辅助放化疗对局部进展期中低位直肠癌患者的临床疗效,研究相关临床因素对远期生存的影响。方法 收集我院2010-2014年收治的101例局部进展期中低位直肠癌患者的临床资料,全部患者完成术前调强放疗DT45~50.4 Gy,同步给予奥沙利铂+卡培他滨/氟尿嘧啶或单药卡培他滨化疗,于新辅助治疗后4-13周行全直肠系膜切除术(TME)。评估近期疗效及远期预后,Kaplan-Meier法计算总生存(OS)、无瘤生存(DFS)率,Cox回归模型进行预后因素分析。结果 全组患者总体保肛率53.5%,术后T、N分期及TNM总分期下降率分别为73.26%、67.32%、72.3%,病理完全缓解率16.8%;中位随访41个月,3年OS、DFS、局部复发、远处转移率分别为82.2%、80.7%、7.2%、12.1%。单因素分析显示ypT、ypN分期是影响患者3年OS、DFS、远处转移的相关因素(P均<0.05);多因素分析显示ypT分期是影响患者3年OS因素,ypT、ypN分期是影响患者3年DFS因素(P均<0.05)。结论 新辅助放化疗联合TME治疗局部进展期中低位直肠癌,使部分患者达到术前降期,提高保肛率,且远期预后表现良好,ypT、ypN分期与患者预后相关。