肿瘤细胞减灭术联合腹腔热灌注化疗（CRS/HIPEC）治疗结直肠癌腹膜转移的现状和进展

腹膜是结直肠癌转移的好发部位。结直肠癌发生腹膜转移长期以来被认为预后很差,主要采用姑息性手段治疗。尽管化疗及靶向治疗在结直肠癌治疗上有很大进展,但对于腹膜转移的结直肠癌疗效并不理想。最近越来越多的证据表明,肿瘤细胞减灭术(CRS)联合腹腔内热灌注化疗(HIPEC)的治疗方法能给这部分患者带来较大的生存获益。本文综述了结直肠癌腹膜转移的诊治现状和相关进展。目前认为CRS联合HIPEC对选择的结直肠癌腹膜转移患者是一种安全有效的治疗模式,但HIPEC能否预防进展期结直肠癌发生腹膜转移,还有待进一步的临床试验研究。     

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。     

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。     

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。     

CD44在腹腔肿瘤腹膜转移中的意义

CD44作为多功能粘附分子，与肿瘤转移的粘附过程密切相关。腹腔肿瘤细胞CD44的表达，促进了肿瘤细胞与腹膜组织的粘附，从而在腹膜转移形成的初始阶段发挥重要作用。腹膜转移过程中常出现与肿瘤转移相关表位结构的CD44分子的表达，主要是CD44变异体的表达，胃癌和卵巢癌尤其明显。对这些变异体的深入研究，有助于阐明腹腔肿瘤腹膜转移的机理。通过抑制CD44的表达或阻断其作用，对腹腔肿瘤的腹膜转移有一定的抑制作用。     

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。     

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。     

CD44在腹腔肿瘤腹膜转移中的意义

CD44作为多功能粘附分子,与肿瘤转移的粘附过程密切相关。腹腔肿瘤细胞CD44的表达,促进了肿瘤细胞与腹膜组织的粘附,从而在腹膜转移形成的初始阶段发挥重要作用。腹膜转移过程中常出现与肿瘤转移相关表位结构的CD44分子的表达,主要是CD44变异体的表达,胃癌和卵巢癌尤其明显。对这些变异体的深入研究,有助于阐明腹腔肿瘤腹膜转移的机理。通过抑制CD44的表达或阻断其作用,对腹腔肿瘤的腹膜转移有一定的抑制作用。     

影响原发性腹膜后肿瘤手术患者预后的危险因素分析

背景原发性腹膜后肿瘤多为恶性肿瘤,其病因多种多样.分级、切除范围和肿瘤完整性等参数已被证明影响预后.目的探索影响原发性腹膜后肿瘤手术患者术后生存的危险因素.方法73例腹膜后肿瘤根治性手术的患者分为无瘤生存组(47例)、复发死亡组(26例).收集并分析影响患者术后无瘤生存的因素,包括年龄、肿瘤长径、淋巴结转移、首发症状、肿瘤类型、肿瘤分化程度以及是否合并其他系统疾病等.结果原发性腹膜后肿瘤术后5年无瘤生存率为64.4%(47/73).对影响原发性腹膜后肿瘤术后无瘤生存率的因素进行单因素分析结果显示:年龄(P0.05),肿瘤长径(P0.05),淋巴结转移(P0.05),首发症状(P0.05),肿瘤类型(P 0.05),肿瘤分化程度(P 0.05)共6项因素与腹膜后肿瘤术后无瘤生存率相关.多因素Cox回归分析结果提示首发症状(P0.05)以及肿瘤类型(P 0.05)影响腹膜后肿瘤患者术后无瘤生存率的独立危险因素.结论首发症状以及肿瘤类型是影响腹膜后肿瘤患者术后无瘤生存率的关键.     

放射性125Ⅰ粒子组织间植入治疗腹膜后淋巴结转移15例临床观察

目的探讨放射性125Ⅰ粒子组织间植入治疗腹膜后淋巴结转移的疗效及安全性。方法采用治疗计划系统（TPS）模拟布源求出术中所需粒子的总活度及数量,在CT引导下对15例腹膜后淋巴结转移患者行肿瘤内125Ⅰ粒子植入治疗。结果12例疼痛症状明显改善,13例2个月后CT复查显示病灶有不同程度缩小。结论125Ⅰ放射性粒子组织间植人治疗腹膜后淋巴结转移疗效高、创伤小、并发症少。     

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy: Where are we?

Peritoneal surface malignancies are generally associated with poor prognosis. In daily clinical routine, systemic chemotherapy is still considered the only reasonable therapy despite of encouraging results of cytoreductive surgery (CRS) along with intraperitoneal hyperthermic chemotherapy (HIPEC). The Achilles heel of CRS and HIPEC is appropriate patient selection and precise surgical technique preventing patients from excessive morbidity and mortality. Given these findings, new concepts of second look surgery for high risk patients allow detection of peritoneal spread ahead of clinical symptoms or presence of peritoneal masses reducing perioperative morbidity. In addition, personalized intraperitoneal chemotherapy might further improve outcome by appreciating individual tumor biology. These days, every physician should be aware of CRS and HIPEC for treatment of peritoneal surface malignancies. Since there is now sufficient data for the superiority of CRS and HIPEC to systemic chemotherapy in selected patients, our next goal should be providing this strategy with minimal morbidity and mortality even in the presence of higher tumor load.     

CD31 and D2-40 Contribute to Peritoneal Metastasis of Colorectal Cancer by Promoting Epithelial-Mesenchymal Transition

Background/AimsColorectal cancer (CRC) patients often exhibit peritoneal metastasis, which negatively impacts their prognosis. CD31 and D2-40 have recently been suggested to be predictors of breast cancer prognosis, but their role in colorectal peritoneal metastasis (CRPM) remains unknown.MethodsThe expression profiles of CD31 and D2-40 were analyzed in CRC patients with or without CRPM and in CRC cell lines with increasing metastatic potential. Overexpression and short hairpin RNA knockdown assays were performed in CRC cells, and the effects of these alterations on epithelial-mesenchymal transition (EMT) in vitro, growth of xenograft tumors in vivo, and peritoneal metastasis potential in a mouse model of CRPM were examined.ResultsThe expressions of CD31 and D2-40 were upregulated in CRC tumor tissues and was elevated further in tumor tissues from patients with CRPM. CD31 and D2-40 expression levels exhibited increasing trends parallel to the EMT potential of CRC cells. CD31 and D2-40 are essential for CRC cell EMT in vitro as well as for xenograft tumor growth and peritoneal metastasis in vivo.ConclusionsCD31 and D2-40 contribute to CRPM by promoting EMT and may serve as prognostic markers and therapeutic targets for CRC, particularly in patients with peritoneal metastasis.     

Colorectal peritoneal metastases: Optimal management review

The peritoneum is a common site of dissemination for colorrectal cancer, with a poorer prognosis than other sites of metastases. In the last two decades, it has been considered as a locoregional disease progression and treated as such with curative intention treatments. Cytoreductive surgery(CRS) and hyperthermic intraperitoneal chemotherapy(HIPEC) is the actual reference treatment for these patients as better survival results have been reached as compared to systemic chemotherapy alone, but its therapeutic efficacy is still under debate. Actual guidelines recommend that the management of colorectal cancer with peritoneal metastases should be led by a multidisciplinary team carried out in experienced centers and consider CRS + HIPEC for selected patients. Accumulative evidence in the last three years suggests that this is a curative treatment that may improve patients disease-free survival, decrease the risk of recurrence, and does not increase the risk of treatment-related mortality. In this review we aim to gather the latest results from referral centers and opinions from experts about the effectiveness and feasibility of CRS + HIPEC for treating peritoneal disease from colorectal malignancies.     

Therapeutic options for peritoneal metastasis arising from colorectal cancer

Peritoneal metastasis is a common sign of advanced tumor stage, tumor progression or tumor recurrence in patients with colorectal cancer. Due to the improvement of systemic chemotherapy, the development of targeted therapy and the introduction of additive treatment options such as cytoreductive surgery(CRS) and hyperthermic intraperitoneal chemotherapy(HIPEC), the therapeutic approach to peritoneal metastatic colorectal cancer(pm CRC) has changed over recent decades, and patient survival has improved. Moreover, in contrast to palliative systemic chemotherapy or best supportive care, the inclusion of CRS and HIPEC as inherent components of a multidisciplinary treatment regimen provides a therapeutic approach with curative intent. Although CRS and HIPEC are increasingly accepted as the standard of care for selected patients and have become part of numerous national and international guidelines, the individual role, optimal timing and ideal sequence of the different systemic, local and surgical treatment options remains a matter of debate. Ongoing and future randomized controlled clinical trials may help clarify the impact of the different components, allow for further improvement of patient selection and support the standar-dization of oncologic treatment regimens for pm CRC. The addition of further therapeutic options such as neo-adjuvant intraperitoneal chemotherapy or pressurized intraperitoneal aerosol chemotherapy, should be investig-ated to optimize therapeutic regimens and further improve the oncological outcome.     

Peritoneal lavage cytology and carcinoembryonic antigen determination in predicting peritoneal metastasis and prognosis of gastric cancer

AIM: To evaluate the role of peritoneal lavage cytology (PLC) and carcinoembryonic antigen (CEA) determination of peritoneal washes (pCEA) in predicting the peritoneal metastasis and prognosis after curative resection of gastric cancer. METHODS: PLC and radioimmunoassay of CEA were performed in peritoneal washes from 64 patients with gastric cancer and 8 patients with benign diseases. RESULTS: The positive rate of pCEA (40.6%) was significantly higher than that of PLC (23.4%) (P<0.05). The positive rates of PLC and pCEA correlated with the depth of tumor invasion and lymph node metastasis (P<0.05). pCEA was found to have a higher sensitivity and a lower false-positive rate in predicting peritoneal metastasis after curative resection of gastric cancer as compared to PLC. The 1-, 3-, and 5-year survival rates of patients with positive cytologic findings or positive pCEA results were significantly lower than those of patients with negative cytologic findings or negative pCEA results (P<0.05). Multivariate analysis indicated that pCEA was an independent prognostic factor for the survival of patients with gastric cancer. CONCLUSION: Intraoperative pCEA is a more sensitive and reliable predictor of peritoneal metastasis as well as prognosis in patients with gastric cancer as compared to PLC method.     

Chinese expert consensus on cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for peritoneal malignancies

Locoregional spread of abdominopelvic malignant tumors frequently results in peritoneal carcinomatosis(PC). The prognosis of PC patients treated by conventional systemic chemotherapy is poor, with a median survival of 6 mo. However, over the past three decades, an integrated treatment strategy of cytoreductive surgery(CRS) + hyperthermic intraperitoneal chemotherapy(HIPEC) has been developed by the pioneering oncologists, with proved efficacy and safety in selected patients. Supported by several lines of clinical evidence from phases Ⅰ, Ⅱ and Ⅲ clinical trials, CRS + HIPEC has been regarded as the standard treatment for selected patients with PC in many established cancer centers worldwide. In China, an expert consensus on CRS + HIPEC has been reached by the leading surgical and medical oncologists, under the framework of the China Anti-Cancer Association. This expert consensus has summarized the progress in PC clinical studies and systematically evaluated the CRS + HIPEC procedures in China as well as across the world, so as to lay the foundation for formulating PC treatment guidelines specific to the national conditions of China.     

Cytoreductive surgery and intraperitoneal chemotherapy for colorectal peritoneal metastases

AIM: To systematically review the available evidence regarding cytoreductive surgery (CRS) and intraperitoneal chemotherapy (IPC) for colorectal peritoneal metastases (CPM).METHODS: An electronic literature search was carried out to identify publications reporting oncological outcome data (overall survival and/or disease free survival and/or recurrence rates) following CRS and IPC for treatment of CPM. Studies reporting outcomes following CRS and IPC for cancer subtypes other than colorectal were only included if data were reported independently for colorectal cancer-associated cases; in addition studies reporting outcomes for peritoneal carcinomatosis of appendiceal origin were excluded.RESULTS: Twenty seven studies, published between 1999 and 2013 with a combined population of 2838 patients met the predefined inclusion criteria. Included studies comprised 21 case series, 5 case-control studies and 1 randomised controlled trial. Four studies provided comparative oncological outcome data for patients undergoing CRS in combination with IPC vs systemic chemotherapy alone. The primary indication for treatment was CPM in 96% of cases (2714/2838) and recurrent CPM (rCPM) in the remaining 4% (124/2838). In the majority of included studies (20/27) CRS was combined with hyperthermic intraperitoneal chemotherapy (HIPEC). In 3 studies HIPEC was used in combination with early post-operative intraperitoneal chemotherapy (EPIC), and 2 studies used EPIC only, following CRS. Two studies evaluated comparative outcomes with CRS + HIPEC vs CRS + EPIC for treatment of CPM. The delivery of IPC was performed using an “open” or “closed” abdomen approach in the included studies.CONCLUSION: The available evidence presented in this review indicates that enhanced survival times can be achieved for CPM after combined treatment with CRS and IPC.     

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。