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。     

结直肠癌的影像学诊断研究新进展

结直肠癌是消化系统最常见的恶性肿瘤之一,早发现原发病灶、转移灶以及复发病灶可以指导临床治疗和评估预后。影像诊断在结直肠癌的诊疗过程中发挥了重要作用。现在随着双源CT、多模态MRI技术、PET/CT、超声造影等新技术的发展,提高了对肿瘤分期的准确性,其多种参数还可进一步评估肿瘤的分级、血供等,有助于肿瘤的精准诊断与个体化治疗。本文对影像学方法在结直肠癌诊断及肝转移中的诊疗现状和进展进行综述。     

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。     

超声造影定量评估新辅助治疗后直肠癌的微循环血流及与微血管密度相关性

背景新辅助治疗有助于进一步提高直肠癌患者的术后疗效,降低肿瘤复发率,改善患者生活质量.准确评估其疗效意义重大.超声造影(contrast-enhanced ultrasound,CEUS)作为一种能实时显示目标组织微循环状态的超声新技术,能为临床评估疗效提供可靠的血流动力学参考.目的探讨CEUS定量评估新辅助治疗后直肠癌的微循环血流灌注状态变化,及其与微血管密度(microvessel density,MVD)相关性.方法选取在我院行新辅助治疗的进展期直肠癌患者106例,所有患者于治疗前后行CEUS检查,测定病灶微循环血流灌注参数,并与手术后标本MVD进行比较分析.结果新辅助治疗后病灶最大直径较治疗前明显减少,差异有统计学意义(P<0.05);新辅助治疗后病灶曲线下面积(area under the curve,AUC)、峰值强度(peak intensity,PI)较治疗前明显下降,差异有统计学意义(P<0.05);新辅助治疗后病灶PI、AUC分别与MVD呈正相关(r=0.82,P<0.05;r=0.79,P<0.05).结论CEUS能客观反映直肠癌微循环血流灌注状态,其血流灌注参数与MVD有较好相关性,可为临床评估直肠癌新辅助治疗效果提供血流动力学参考.     

结直肠癌肝转移的外科治疗

结直肠癌患者容易出现肝转移,肝转移是影响结直肠癌患者预后的主要原因之一.手术是目前治愈结直肠癌肝转移的唯一方法.本文主要总结了近年来结直肠癌肝转移患者肝转移病灶的手术进展情况:包括通过新辅助化疗或分阶段肝切除等方法提高肝转移病灶的手术切除率、肝转移灶切缘对患者预后的影响、同时性结直肠癌肝转移患者手术时机的选择、腹腔镜下肝转移灶切除的影响及优势,肝移植在结直肠癌肝转移患者中的应用等.本文旨在结合结直肠肝转移的手术进展和患者的实际情况,为患者选择最佳的治疗方案,从而提高患者的生存时间.     

同时性多原发结直肠癌与散发性结直肠癌患者结肠镜随访的配对分析

目的研究同时性多原发结直肠癌与散发性结直肠癌患者异时性进展期腺瘤(MAA)的发生率。方法纳入2008年1月1日至2022年9月30日在首都医科大学附属北京世纪坛医院接受结直肠癌手术(外科手术或内镜切除)并进行3年结肠镜随访的结直肠癌患者。患者在术后6～36个月内完成≥2次结肠镜随访, 且2次结肠镜检查间隔时间>6个月。收集患者年龄, 性别, 肿瘤部位、分期、病理学特征, 合并基础疾病情况, 术前癌胚抗原、血红蛋白等实验室检查结果, 基线结肠镜检查结果, MAA检出情况等资料。根据年龄(±2岁)、性别、原发肿瘤部位(同一节段)和肿瘤分期将同时性多原发结直肠癌患者与散发性结直肠癌患者按照病灶数1∶1进行倾向性评分匹配法配对。计算同时性多原发结直肠癌和散发性结直肠癌患者MAA的累积发生风险。采用Cox比例风险回归模型分析MAA发生的影响因素。结果共纳入814例结直肠癌患者进行配对。配对后, 同时性多原发结直肠癌患者36例(78个癌灶), 散发性结直肠癌患者78例(78个癌灶)。同时性多原发结直肠癌组患者1、2、3年MAA的累积发生率分别为11.1%(4/36)、22.2%(8/36)、...     

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。     

经内镜切除或手术治疗后早期结直肠癌的病理分析和疗效评价

背景:早期结直肠癌因淋巴结转移率低而预后良好,如何提高其检出率并选择合理的治疗方式是亟待解决的临床问题。目的:分析早期结直肠癌在内镜切除或手术后的病理特点,评价内镜切除的疗效。方法:回顾性分析503例接受内镜切除或外科手术的早期结直肠癌病灶的病理资料,分析影响早期结直肠癌浸润深度、淋巴结转移的危险因素,并评价内镜切除的疗效。结果:早期结直肠癌的检出率为10.7%,淋巴结总转移率为1.2%(6/503),其中黏膜高级别瘤变的淋巴结转移率为0%(0/247),黏膜下层癌为2.3%(6/256);内镜切除组黏膜下浅层癌的淋巴结转移率为0%(0/31)。肿瘤位置、肿瘤直径、组织学分型和淋巴结转移对早期结直肠癌的浸润深度有显著影响(P0.05)。内镜切除组病灶的整块切除率为96.0%,完全切除率为94.2%,治愈性切除率为82.1%。浸润深度是导致分块切除、不完全切除以及非治愈性切除的危险因素(P0.05)。结论:早期结直肠癌的淋巴结转移率极低,术前充分判断病灶的性质和浸润深度,有助于选择更为合理的治疗方式。对可能浸润至黏膜下层的病灶行内镜切除应更为慎重,以期提高内镜切除的疗效。     

结直肠癌肝转移新辅助治疗研究进展

结直肠癌的发病率及死亡率在全世界范围内逐年上升,其主要的死亡原因是肝转移。现代医学技术快速发展推动了诊治理念不断更新。个体化治疗及多学科综合治疗协作组（MDT）诊治理念的提出,外科技术以及局部治疗的迅速发展,使患者的生存期得以明显延长。结直肠癌肝转移新辅助治疗的应用有助于降低肿瘤分期,提高手术切除率,进而转化为患者生存获益,这一点在其他实体瘤中也已得到证实。但新辅助治疗是否延长所有患者生存期以及患者能否从局部治疗中获益仍存在争议,本文就结直肠癌肝转移新辅助治疗研究进展进行综述。     

CEA在评估直肠癌新辅助放化疗后肿瘤退缩中的意义

目的探讨局部晚期直肠癌术前新辅助放化疗疗效的预测因素,以指导直肠癌的个体化治疗。 方法回顾性分析南京医科大学第一附属医院2014年3月至2015年3月间收治的28例局部进展期直肠癌患者的临床病理资料,利用化学发光法检测新辅助放化疗前、后直肠癌患者血清癌胚抗原（carcino embryonie antigen,CEA）水平,以放化疗后肿瘤TNM分期降期与否和肿瘤消退程度（肿瘤长径）作为同步放化疗疗效的判断标准,分析CEA检测值的变化与直肠癌患者新辅助治疗疗效及预后等临床特征之间的关系。 结果病理完全缓解组(pathologic complete response,pCR)组与非pCR组患者,CEA的水平在新辅助治疗前后无统计学差异(p=0.069),新辅助治疗后,CEA的下降程度在两组中未见差异（p=0.827）。经新辅助治疗后肿瘤长径退缩显著组,CEA下降程度也较显著,CEA下降≥50%组内,新辅助治疗后肿瘤长径退缩≥25%的患者占70.6%,CEA下降<50%组内,此部分患者仅占54.6%。 结论新辅助放化疗后CEA明显下降的患者其肿瘤退缩更显著,提示CEA可能作为一项直观的评估直肠癌新辅助放化疗的疗效指标。     

Multimodale Therapie des kolorektalen Karzinoms

Adjuvant chemotherapy for resected stage III colon cancer is indicated for all patients, including elderly patients >70 years. In general, adjuvant oxaliplatin-fluoropyrimidine chemotherapy should be started within 6 weeks after tumor resection and should be given for a period of 6 months. However, patients aged >70 should receive fluoropyrimidine mono-chemotherapy. This mono-therapy, but not an oxaliplatin-based combination, can also be considered for patients with standard risk stage II tumors without microsatellite instability. In stage II patients with a high risk constellation adjuvant oxaliplatin-fluoropyrimidine combination therapy should be considered. Patients with stage II and III rectal cancer require neoadjuvant radiochemotherapy with fluoropyrimidine followed by adjuvant fluoropyrimidine treatment. There is no role for the use of VEGF- or EGFR-antibodies in the adjuvant therapy of colon cancer or in neoadjuvant therapy of rectal cancer. The prognosis of patients with primary resectable colorectal liver metastases may be improved by adjuvant or perioperative chemotherapy, while neoadjuvant systemic chemotherapy frequently facilitates potential curative resection of initially non-resectable liver metastases.     

Sequential endoscopic ultrasound identifies predictive variables for relapse-free follow-up after neoadjuvant chemotherapy in gastric cancer

Background: The accuracy of endosonographic tumor staging after neoadjuvant therapy is less reliable than in primary staging. Therefore, the value of sequential endosonographic examinations after neaodjuvant chemotherapy in gastro-esophageal cancer is discussed controversially. Previous data suggest, that endoscopic ultrasound (EUS) after neoadjuvant treatment using other variables than classic uTN-criteria may identify patients with a better prognosis.

Methods: In 67 patients with locally advanced gastric cancer treated in curative intent, we performed EUS before and after neoadjuvant chemotherapy. Endosonographic yTN-stage was compared to pathohistological yTN-stage after curative resection. The uTN-stage, yuTN-stage, maximal tumor thickness and maximal lymph node diameter as well as the shift of these variables after neoadjuvant therapy were analyzed for their usefulness to predict recurrence-free follow-up.

Results: Accuracy of EUS for yTN-staging after neoadjuvant therapy was poor, especially in lower tumor stages. However, three heavily correlated variables analyzed by sequential EUS could be used for the prediction of prognosis: low endosonographic tumor stage (yuT0–2) after neoadjuvant chemotherapy, a decrease of two or more steps in uT-stage and a maximal tumor thickness of <15?mm after chemotherapy were significantly associated with recurrence-free follow-up. Endosonographic T-stage before neoadjuvant therapy, as well as lymph node variables before or after chemotherapy, were of no predictive value.

Conclusion: In spite of poor concordance between endosonographic and pathohistological TN-stage after neoadjuvant treatment, sequential EUS, performed before and after neoadjuvant therapy, possibly identify patients at risk for tumor relapse after multimodal treatment in gastric cancer. This finding should be validated in a larger patient cohort.     

结肠癌伴可切除肝肺转移术前新辅助化疗一例

目前新辅助治疗对于转移性肠癌的治疗优势仍有争议。本例为初始可切除肝肺转移的肠癌患者实施了术前新辅助治疗，现将治疗过程中的一些经验和教训与大家分享。     

Bevacizumab-based neoadjuvant chemotherapy for colorectal cancer liver metastases: Pitfalls and helpful tricks in a review for clinicians

Bevacizumab added to chemotherapy has shown encouraging efficacy in the neoadjuvant therapy of colorectal cancer liver metastases. In absence of biological predictor factors of efficacy to bevacizumab-based treatment, the assessment of response may be a crucial point to select patients who may benefit the most from surgery. At the same time the pathological response after liver resection could represent a guide for the next therapeutic plan. In the pre-surgical phase, conventional computed tomography and response evaluation with RECIST criteria may underestimate the response to anti-angiogenic drugs. Modified computed tomography criteria of response, morphologic changes as well as novel imaging techniques and metabolic assessment by fluorodeoxyglucose positron emission tomography seem to be promising methods for the assessment of response and for leading the clinical choices. Pathological response at the time of surgery is an important prognostic factor and a surrogate of survival for resected patients. Different classification criteria to assess pathological response have been developed, residual viable tumor, tumor regression grade (TRG), modified TRG and tumor thickness at the tumor-normal interface, but to date a superiority of one approach over the others has not been clearly established. In this review, we evaluate the available data with the aim to help the clinicians in the pre- and post-surgical care of patient with colorectal cancer liver metastases treated with bevacizumab-based neoadjuvant strategy.     

Multi-modality treatment of colorectal liver metastases

Liver metastases synchronously or metachronously occur in approximately 50% of colorectal cancer patients. Multimodality comprehensive treatment is the best therapeutic strategy for these patients. However, the optimal pattern of multimodality therapy is still controversial, and it raises several significant concerns. Liver resection is the most important treatment for colorectal liver metastases. The definition of resectability has shifted to focus on the completion of R0 resection and normal liver function maintenance. The role of neoadjuvant and adjuvant chemotherapy still needs to be clarified. The management of either progression or complete remission during neoadjuvant chemotherapy is challenging. The optimal sequencing of surgery and chemotherapy in synchronous colorectal liver metastases patients is still unclear. Conversional chemotherapy, portal vein embolization, two-stage resection, and tumor ablation are effective approaches to improve resectability for initially unresectable patients. Several technical issues and concerns related to these methods need to be further explored. For patients with definitely unresectable liver disease, the necessity of resecting the primary tumor is still debatable, and evaluating and predicting the efficacy of targeted therapy deserve further investigation. This review discusses different patterns and important concerns of multidisciplinary treatment of colorectal liver metastases.     

Simultaneous surgery for primary colorectal cancer and metastatic lesions?

Approximately 20-25% of patients with colorectal cancer present with liver metastases at the time of diagnosis. Traditionally, resection of the primary tumor has been advocated in order to prevent complications of the primary tumor colorectal cancer in patients with synchronous liver metastases. The published data concerning long-term prognosis in this group of patients are discordant. Although some of the reports show survival benefits from resection of the primary tumor, these studies are retrospective with small number of patients and using single drug chemotherapy. For patients with resectable liver metastases, new studies indicate that progression-free survival is best in patients receiving perioperative chemotherapy. In patients with synchronous nonresectable liver metastases and colorectal cancer, there is no published prospective randomized study comparing initial surgery of the primary tumor with neoadjuvant chemotherapy. However, recent publications show that in patients receiving chemotherapy based on oxaliplatin or irinotecan combined with targeted treatments, the complications associated with the primary tumor are less than 10%. The conclusion should be that today prophylactic surgery of asymptomatic primary colorectal cancer in patients with liver metastases cannot be recommended.     

Therapeutic strategies for hepatic metastasis of colorectal cancer: overview

To determine the treatment strategy for hepatic metastases of colorectal cancer, it is important to take into account whether metastases are still localized in the liver, or whether the tumor has metastasized throughout the body. For liver-limited metastasis, hepatectomy is the therapeutic strategy that offers the best prospect of improving a patient's prognosis if the case is deemed resectable. In cases when surgery is not indicated for hepatic metastases of colorectal cancer, chemotherapy is the first-choice treatment. Chemotherapy for colorectal cancer has made vast strides in recent years through advances such as the development of molecular targeted drugs. In cases where chemotherapy is effective and surgical resection becomes possible (conversion chemotherapy), the long-term prognosis may be good. The value of preoperative chemotherapy in resectable cases (neoadjuvant chemotherapy) has also been reported. The improvement in prognosis achieved by eradicating tiny latent metastases is important in conversion therapy, as well as in neoadjuvant chemotherapy. It will be important to achieve further improvements in the prognoses of patients with hepatic metastases of colorectal cancer through a combination of advances in diagnostic imaging, improvements in surgical techniques, and more effective chemotherapy treatments.     

Predictive and prognostic implications of 4E-BP1, Beclin-1, and LC3for cetuximab treatment combined with chemotherapy in advanced colorectal cancer with wild-type KRAS: Analysis from real-world data

BACKGROUND Colorectal cancer(CRC) is one of the main causes of cancer-related deaths in China and around the world. Advanced CRC(ACRC) patients suffer from a low cure rate though treated with targeted therapies. The response rate is about 50% to chemotherapy and cetuximab, a monoclonal antibody targeting epidermal growth factor receptor(EGFR) and used for ACRC with wild-type KRAS. It is important to identify more predictors of cetuximab efficacy to further improve precise treatment. Autophagy, showing a key role in the cancer progression, is influenced by the EGFR pathway. Whether autophagy can predict cetuximab efficacy in ACRC is an interesting topic.AIM To investigate the effect of autophagy on the efficacy of cetuximab in colon cancer cells and ACRC patients with wild-type KRAS.METHODS ACRC patients treated with cetuximab plus chemotherapy, with detailed data and tumor tissue, at Sun Yat-sen University Cancer Center from January 1, 2005,to October 1, 2015, were studied. Expression of autophagy-related proteins[Beclin1, microtubule-associated protein 1 A/B-light chain 3(LC3), and 4 Ebinding protein 1(4 E-BP1)] was examined by Western blot in CRC cells and by immunohistochemistry in cancerous and normal tissues. The effect of autophagy on cetuximab-treated cancer cells was confirmed by MTT assay. The associations between Beclin1, LC3, and 4 E-BP1 expression in tumor tissue and the efficacy of cetuximab-based therapy were analyzed.RESULTS In CACO-2 cells exposed to cetuximab, LC3 and 4 E-BP1 were upregulated, and P62 was downregulated. Autophagosome formation was observed, and autophagy increased the efficacy of cetuximab. In 68 ACRC patients,immunohistochemistry showed that Beclin1 levels were significantly correlated with those of LC3(0.657, P 0.001) and 4 E-BP1(0.211, P = 0.042) in ACRC tissues.LC3 was significantly overexpressed in tumor tissues compared to normal tissues(P 0.001). In 45 patients with wild-type KRAS, the expression levels of these three proteins were not related to progression-free survival; however, the expression levels of Beclin1(P = 0.010) and 4 E-BP1(P = 0.005), pathological grade(P = 0.002), and T stage(P = 0.004) were independent prognostic factors for overall survival(OS).CONCLUSION The effect of cetuximab on colon cancer cells might be improved by autophagy.LC3 is overexpressed in tumor tissues, and Beclin1 and 4 E-BP1 could be significant predictors of OS in ACRC patients treated with cetuximab.