结直肠癌腹膜转移癌的诊治进展

［摘要］　结直肠癌腹膜转移癌（CRC PC）的诊断和治疗已经取得很大进展。过去CRC PC被认为是肿瘤晚期并全身转移的表现,一般只行姑息治疗,预后差;如今适当的CRC PC患者经过积极的治疗可显著改善预后。肿瘤细胞减灭术（CRS）+腹腔热灌注化疗（HIPEC）已成为治疗CRC PC的有效手段。该文综述近年来CRC PC的诊治进展。     

肿瘤细胞减灭术加腹腔热灌注化疗治疗结直肠癌腹膜转移癌的临床研究

目的：探讨肿瘤细胞减灭术（CRS）加腹腔热灌注化疗（HIPEC）治疗结直肠癌腹膜转移癌（ CRC PC）的疗效及安全性。方法选取结直肠癌腹膜转移癌（ CRC PC）患者67例,随机分为治疗组（ CRS＋HIPEC）38例,对照组（CRS＋静脉辅助化疗）29例,比较两组的生存期、生存率、术后并发症及化疗毒副作用。结果治疗组中位生存期23.0个月,显著长于对照组的11.0个月（ P＜0.01）,治疗组1、2、3年生存率分别为70.9％、45.7％、8.2％,分别优于对照组的68.8％、21.2％、0％。术后并发症发生率两组相似（ P＞0.05）。化疗毒副作用：对照组恶心呕吐、白细胞减少、血小板减少发生率较治疗组高（P＜0.01）,而治疗组腹胀、腹泻发生率较对照组高（ P＜0.01或P＜0.05）;两组其他毒副作用相似（ P＞0.05）。结论 CRS＋HIPEC治疗CRC PC能明显延长患者生存期,并发症和化疗毒副作用并没有明显增加。     

腹膜转移的结肠癌患者MDT诊治二例

本文描述了2例异时性腹膜转移的结肠癌病例的多学科诊治过程。1例多发转移,1例单发转移。这两例患者经MDT讨论后都首先采用了肿瘤减灭术联合腹腔热灌注化疗的治疗模式（cytoreductive surgery,CRS/hyperthermic intraperitoneal peroperative chemotherapy,HIPEC）,单发转移的患者目前获得了12个月的无病生存期（disease-free survival,DFS）,而多发转移的患者也获得了12个多月的总生存期（overall survival,OS）。目前发现与结直肠癌腹膜转移患者OS相关的因素包括肿瘤减灭术（CRS）完全程度和肿瘤累及的范围（腹膜转移癌指数）等。因此,对于结直肠癌的腹膜转移患者,评估病变范围极其重要,对于较局限的腹膜转移,多学科的综合诊治和积极的治疗手段能改善这部分患者的生存时间和生存质量。     

肿瘤细胞减灭术及腹腔热灌注化疗联合肝切除治疗结直肠癌腹膜转移合并肝转移的临床疗效

目的探讨肿瘤细胞减灭术（CRS）及腹腔热灌注化疗（HIPEC）联合肝切除治疗结直肠癌腹膜转移（CRPM）合并肝转移（LM）的安全性及有效性。 方法回顾性收集中国医学科学院肿瘤医院结直肠外科自2017年6月至2019年6月采用CRS+HIPEC联合肝切除治疗的16例CRPM合并孤立LM患者的临床病理资料。 结果男性6例,女性10例,中位年龄62岁。全组患者接受CRS+HIPEC联合同步肝切除,肝脏转移瘤均获得完整切除。中位总生存期25个月,中位无病生存期9个月。1年及3年总生存率分别为75.0%及37.0%,1年及3年无病生存率分别为50.0%及9.4%。6例（37.5%）出现轻度并发症（Clavien-Dindo Ⅰ~Ⅱ）,4例（25.0%）出现严重并发症（Ⅲ~Ⅳ）。 结论CRPM合并孤立的、能完整切除的LM的患者接受CRS+HIPEC联合同期肝切除是安全可行的,同时可为患者带来一定生存获益。     

中国恶性肿瘤整合诊治指南-肛管癌部分

目的探讨肿瘤细胞减灭术（CRS）及腹腔热灌注化疗（HIPEC）联合肝切除治疗结直肠癌腹膜转移（CRPM）合并肝转移（LM）的安全性及有效性。 方法回顾性收集中国医学科学院肿瘤医院结直肠外科自2017年6月至2019年6月采用CRS+HIPEC联合肝切除治疗的16例CRPM合并孤立LM患者的临床病理资料。 结果男性6例，女性10例，中位年龄62岁。全组患者接受CRS+HIPEC联合同步肝切除，肝脏转移瘤均获得完整切除。中位总生存期25个月，中位无病生存期9个月。1年及3年总生存率分别为75.0%及37.0%，1年及3年无病生存率分别为50.0%及9.4%。6例（37.5%）出现轻度并发症（Clavien-Dindo Ⅰ~Ⅱ），4例（25.0%）出现严重并发症（Ⅲ~Ⅳ）。 结论CRPM合并孤立的、能完整切除的LM的患者接受CRS+HIPEC联合同期肝切除是安全可行的，同时可为患者带来一定生存获益。     

腹膜转移癌诊疗决策中评分系统的研究进展

腹膜转移是肿瘤的晚期阶段，预后较差。肿瘤细胞减灭术联合腹腔热灌注化疗（CRS+HIPEC）可以显著改善患者预后。患者的预后往往和腹膜疾病的严重程度和CRS肿瘤细胞减灭的程度相关。在术前和术中有各种评分系统合理评估患者腹膜肿瘤负荷，本文对腹膜转移癌诊疗决策中评分系统展开综述。     

胃癌腹膜转移临床诊疗的新进展

胃癌是我国最常见且高病死率的恶性肿瘤之一.造成其病死率高的原因主要是胃癌转移,其中腹膜转移是胃癌最常见转移方式,占50%以上.胃癌一旦出现腹膜转移则临床病理已属Ⅳ期,提示预后极差.因而,胃癌腹膜转移的早期预防及发生转移后的有效治疗对胃癌患者预后改善有着极其重要的临床价值.本文阐述关于胃癌伴腹膜转移的形成机制、生物标志物及影像学诊断方法以及包括新辅助腹腔内与全身联合化疗(neoadjuvant intraperitoneal-systemic chemotherapy,NIPS)、肿瘤减负荷手术联合腹腔内温热化疗(cytoreductive surgery+hyperthermic intraperitoneal chemotherapy,CRS+HIPEC)、术后早期腹腔内化疗(early postoperative intraperitoneal chemotherapy,EPIC)、广泛的术中腹腔灌洗(extensive intraoperative peritoneal lavage,EIPL)、分子靶向治疗及新型药物输送系统等在内的多种治疗方式的临床研究新进展.     

恶性腹膜间皮瘤的诊断和治疗现状

恶性腹膜间皮瘤(malignant peritoneal mesothelioma,MPM)是原发于腹膜间皮细胞的一种罕见恶性肿瘤,通常与接触石棉有关,预后不良,平均生存期6-12 mo,早期诊断和有效治疗十分困难.MPM大约占全部恶性间皮瘤的10%-15%.其主要症状为腹痛、腹胀、腹部包块、腹水、体质量减轻、发热和呕吐等.计算机断层扫描(computed tomography,CT)、磁共振成像、正电子发射计算机断层扫描/CT、血清肿瘤标志物、分子生物标志物、腹腔镜活检、组织病理学、细胞学、免疫组织化学以及电子显微镜技术已被用于MPM的诊断和随访.此外,本文还重点阐述了MPM的治疗进展,包括细胞减灭术(cytoreductive surgery,CRS)联合腹腔热灌注化疗(hyperthermic intraperitoneal chemotherapy,HIPEC)、化学治疗、放射治疗、分子靶向治疗、pH敏感的紫杉醇膨胀性纳米粒子靶向治疗、免疫治疗等.目前,CRS/HIPEC仍是治疗晚期MPM患者的唯一有效方法.     

经肝动脉化疗栓塞术治疗结直肠癌肝转移的研究进展

肝脏是公认的结直肠癌最普遍的转移器官,根治性切除术被认为是唯一可能治愈结直肠癌肝转移的治疗方案。但仅有约20%的患者能够接受手术治疗。对于已丧失手术机会的患者,经肝动脉化疗栓塞术(TACE)是被国内外学者广泛采用的首选治疗方案之一。介绍了现阶段临床上TACE治疗结直肠癌肝转移的应用基础、适应证、禁忌证、疗效、化疗药物及栓塞剂等。认为TACE是一种疗效肯定、微创、副反应少的姑息性治疗方案,可以作为不可切除结直肠癌肝转移患者的首选治疗方案。     

结直肠癌腹膜转移治疗策略——AJCC第八版分期的启示

结直肠癌腹膜转移发生率较高且预后差。美国癌症联合委员会（AJCC）第八版癌症分期系统进一步更新远处转移（M）的分期,新增M1c期,即结直肠癌腹膜转移。重视腹膜转移的诊治在我国有着重要作用。近年来,对结直肠癌腹膜转移的机制及治疗等认识程度不断增加,对其治疗效果也有了很大的提高。本文我们将探讨结直肠癌腹膜转移的治疗策略。     

结直肠癌术后腹腔热灌注化疗的护理

结直肠癌是我国最常见的恶性肿瘤之一,随着诊疗技术的不断进步,其5年生存率在不断提高。然而,仍有部分患者确诊时已有腹腔种植转移或根治性术后很快出现腹腔种植转移,其5年生存率极差。目前,已有临床研究证实细胞减瘤术加腹腔热灌注化疗是治疗结直肠癌腹腔种植转移的有效方法,能有效提高结直肠癌患者的生活质量和延长生存期。本文就此对结直肠癌术后应用腹腔热灌注化疗的护理经验进行综述,为临床护理提供依据,改善患者的治疗效果,全面提高护理质量。     

Clinical benefit of surgery for stage IV colorectal cancer with synchronous peritoneal metastasis

Background

Peritoneal metastasis is well-known as a poor prognostic factor in patients with colorectal cancer. It is important to improve the prognosis of patients with colorectal cancer and synchronous peritoneal metastasis. This study aimed to clarify the factors affecting R0 resection and the prognosis of colorectal cancer patients with synchronous peritoneal metastasis.

Methods

We investigated the data of patients with stage IV colorectal cancer between 1991 and 2007 in 16 hospitals that were members of the Japanese Society for Cancer of the Colon and Rectum.

Results

Of the 564 colorectal cancer patients with synchronous peritoneal metastases, 341 also had hematogenous metastases. The 5-year overall survival rates in patients with and without R0 resection were 32.4 and 4.7 %, respectively. A Cox proportional hazards model showed that histologic type of poorly differentiated adenocarcinoma, regional lymph node metastasis, liver metastasis, chemotherapy after surgery, R0 resection, the Japanese classification of peritoneal metastasis, and the size of peritoneal metastases were independent prognostic factors. Of the 564 patients, 28.4 % had R0 resection. The Japanese classification of peritoneal metastasis (P1–P2, p = 0.0024) and absence of hematogenous metastases (p < 0.0001) were associated with R0 resection.

Conclusions

P1–P2 peritoneal metastasis and the absence of hematogenous metastasis were the most favorable factors benefiting from synchronous resection of peritoneal metastasis. In addition, chemotherapy after surgery was essential.     

Benefit of FOLFOX to unresectable liver metastases secondary from colorectal carcinoma in an oncologic emergency

Liver metastasis is an important prognostic factor in colorectal cancer. The efficacy of resection of metastatic lesions in liver metastasis of colorectal cancer is also widely recognized. However, studies on treatment methods of unresectable cases have not been sufficient and obtaining complete remission (CR) for liver metastasis is rare with chemotherapy. Selection of reliable chemotherapy for unresectable liver metastasis is an urgent necessity. The usefulness of oxaliplatin, 5-flurouracil and leucovorin combination therapy (FOLFOX) has recently been reported, but CR of liver metastasis is rare. The current status and new therapeutic significance of FOLFOX therapy are discussed based on the literature of colorectal cancer chemotherapy to date, and the clinical experience in which we obtained CR for liver metastasis is reported. The patient had stage IV rectal cancer, perforative peritonitis, pelvic abscess and simultaneous multiple liver metastasis. The patient underwent an emergency operation using the Hartmann's procedure. Liver metastasis is considered to be a prognostic factor and FOLFOX was selected as the postoperative chemotherapy, CR of the liver metastasis was obtained. FOLFOX was suggested to have new clinical significance in oncologic emergencies against unresectable liver metastasis in colorectal cancer and should serve as adjuvant chemotherapy that will contribute to improvement of treatment results.     

肿瘤标记物结合病理对结直肠癌腹膜转移预判的研究

目的探讨血清CEA、CA19-9、CA125结合临床病理对术前判断是否具有结直肠癌腹膜转移的意义。 方法选取2014年1月至2017年10月在哈尔滨医科大学附属第二临床医学院行手术治疗的结肠癌及肿瘤位于直肠腹膜反折以上的直肠癌患者,共1 215例。其中,无腹膜转移的患者988例,同时性腹膜转移的患者227例,比较两组临床资料。 结果高分化腺癌、中分化腺癌、低分化腺癌、黏液腺癌、印戒细胞癌发生腹膜转移的几率分别为0、5.4%、35.6%、45.3%、75%,病理恶性程度越高越容易出现腹膜转移。血清CEA、CA19-9及CA125三者对结直肠癌腹膜转移的辅助诊断中,以CA125最为敏感,敏感度为100%,曲线下面积为0.897,CA125的这两项明显高于CEA及CA19-9,其特异度与CEA接近,较CA19-9低。CA19-9的特异度最高,为86%,但其灵敏度（47%）、曲线下面积（0.669）为三者中最低。CEA、CA19-9、CA125增高越明显,发生腹膜转移的几率就越大,当CEA＋CA125增高或CA125＋CA19-9增高或CEA＋CA125＋CA19-9增高时,发生腹膜转移的几率分别为65.7%、73.1%、77.3%。 结论通过CEA、CA19-9、CA125结合临床病理等检查的辅助,可以提高术前诊断结直肠癌腹膜转移的准确率,有助于术前判断患者的病情及预后。     

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.     

Impact of Adjuvant Chemotherapy in Patients With Curatively Resected Stage IV Colorectal Cancer

The aim of this study was to investigate the impact of adjuvant chemotherapy on survival of patients who had curative resection for stage IV colorectal cancer.The efficacy of adjuvant chemotherapy after curative resection for stage IV colorectal cancer remains unclear.The database of 3695 patients with stage IV colorectal cancer between 1991 and 2007 collected from 16 member hospitals of the Japanese Society for Cancer of the Colon and Rectum was used for this investigation. The survivals of patients with and without adjuvant chemotherapy after curative resection for stage IV colorectal cancer were evaluated using a propensity score matching method.The data of 689 patients who underwent curative resection for both primary and synchronous metastatic tumors were extracted from the database and used for analysis in this study. The 5-year overall survival rates of the patients with and without adjuvant chemotherapy were 41.8% and 33.9%, respectively. A Cox proportional hazards model showed that adjuvant chemotherapy (P = 0.0042), regional lymph node metastasis (P < 0.0001), and peritoneal metastasis (P = 0.0006) were independent factors for overall survival. In the propensity score-matched cohort, patients with adjuvant chemotherapy had better overall survival than those without (P = 0.026).The present study demonstrated that adjuvant chemotherapy improved overall survival after curative resection for stage IV colorectal cancer. The efficacy of each chemotherapeutic regimen in the adjuvant setting for stage IV colorectal cancer should be clarified in the future.     

Surgical management of patients with peritoneal carcinomatosis of gastrointestinal origin

Peritoneal carcinomatosis is found in approximately 15 % of patients with colorectal cancer during the course of their disease, and is associated with a poor prognosis. Even more patients with gastric cancer develop peritoneal seeding. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) have been introduced in the past decade and have led to 5-year survival rates of 30 to 40 % for selected patients with colorectal cancer and peritoneal carcinomatosis. These numbers have been demonstrated by many retrospective analyses and by prospective Phase II studies. The clinical assessment to select patients who will benefit from the combined therapy and achievement of complete macroscopic cytoreduction both play a crucial role. Less favourabale results have been achieved for patients suffering from stage IV gastric cancer with peritoneal seeding. Promising results were demonstrated for postoperative intraperitoneal chemotherapy following curative gastrectomy. Patients with hepatic, biliary and pancreatic cancers and peritoneal carcinomatosis do not benefit from cytoreductive surgery. There is a need for further multicentre, prospective trials analysing the use of hyperthermic intraperitoneal chemotherapy. They should be conducted in the specialised centres by interdisciplinary teams.     

Current treatment for liver metastases from colorectal cancer

The liver is the commonest site of distant metastasis of colorectal cancer and nearly half of the patients with colorectal cancer ultimately develop liver involved during the course of their diseases. Surgery is the only therapy that offers the possibility of cure for patients with hepatic metastatic diseases. Five-year survival rates after resection of all detectable liver metastases can be up to 40 %. Unfortunately, only 25 % of patients with colorectal liver metastases are candidates for liver resection, while the others are not amenable to surgical resection. Regional therapies such as radiofrequency ablation and cryotherapy may be offered to patients with isolated unresectable metastases but no extrahepatic diseases. Hepatic artery catheter chemotherapy and chemoembolization and portal vein embolization are often used for the patients with extensive liver metastases but without extrahepatic diseases, which are not suitable for regional ablation. For the patients with metastatic colorectal cancer beyond the liver, systemic chemotherapy is a more appropriate choice. Immunotherapy is also a good option when other therapies are used in combination to enhance the efficacy. Selective internal radiation therapy is a new radiation method which can be used in patients given other routine therapies without effects.     

结直肠癌腹膜转移预防和治疗腹腔用药中国专家共识（V 2019）

我国结直肠癌发病率和死亡率均位于恶性肿瘤的前列，腹膜转移作为常见转移部位，是治疗失败的常见原因之一。目前结直肠癌腹膜转移的腹腔预防和治疗性药物种类繁多，但作用剂量和时间尚未形成规范化的治疗模式。因此为了规范术中预防和治疗性腹腔干预方法，中国医师协会结直肠肿瘤专业委员会组织国内相关领域权威专家，制定《结直肠癌腹膜转移预防和治疗腹腔用药中国专家共识》（以下简称《共识》），旨在提高我国结直肠肿瘤的整体诊治水平，延长结直肠癌患者生存时间并改善生活质量。