恶性腹膜间皮瘤在米兰国家癌症中心的治疗进展

弥漫性恶性腹膜间皮瘤（diffuse malignant peritoneal mesothelioma,DMPM）是一种源自腹膜间皮细胞、高度恶性的罕见原发性恶性肿瘤,本文对DMPM的定义、诊断、患者管理流程、米兰国家癌症中心肿瘤细胞减灭术（cytoreductive surgery,CRS）联合腹腔热灌注化疗（hyperthermic intraperitoneal chemotherapy,HIPEC）治疗数据、围手术期化疗对患者预后影响、多囊型腹膜间皮瘤治疗建议、乳头状腹膜间皮瘤治疗建议等进行概述。对本中心DMPM认识与治疗经验进行介绍。随着对这类肿瘤疾病的临床特征和生物学特性进行广泛研究,发现可切除性DMPM应接受CRS+HIPEC,可能会改变患者的自然病程。      

肿瘤细胞减灭术联合腹腔热灌注治疗恶性腹膜间皮瘤的并发症及危险因素分析

目的：分析肿瘤细胞减灭术（cytoreductive surgery,CRS）联合腹腔热灌注化疗（hyperthermic intraperitoneal chemotherapy,HIPEC）治疗恶性腹膜间皮瘤（malignant peritoneal mesothelioma,MPM）的并发症及其影响因素，预防严重不良事件（serious adverse events,SAEs）发生。方法：收集2015年4月至2022年11月在首都医科大学附属北京世纪坛医院行CRS+HIPEC治疗的154例MPM患者临床病理资料，统计术后并发症发生情况，分析影响SAEs的危险因素。结果：共计154例MPM患者接受CRS+HIPEC治疗，1级不良事件10例（8.8%）,2级41例（36.3%）,3级53例（46.9%）,4级7例（6.2%）,5级2例（1.8%）。需要进行抢救的SAEs发生率为5.8%(9/154)，围手术期死亡率1.3%(2/154)。单因素分析表明，腹膜癌指数（peritoneal cancer index,PCI）(P=0.036)、肿瘤细胞减灭程度（completeness ...     

阑尾源性腹膜假黏液瘤单中心诊疗经验

  目的   总结细胞减灭术加腹腔热灌注化疗（cytoreductive surgery & hyperthermic intraperitoneal chemotherapy，CRS+HIPEC）治疗阑尾源性腹膜假黏液瘤（pseudomyxoma peritonei，PMP）的单中心诊疗经验。   方法   回顾性分析2012年1月至2018年12月于航天中心医院收治，病理证实为阑尾源性PMP并经CRS+HIPEC治疗604例患者的临床数据，进行统计学分析。   结果   604例患者经历621次CRS+HIPEC治疗，平均年龄56.7岁，其中女性364例（60.3%），男性240例（39.7%），平均腹膜癌指数（peritoneal cancer index，PCI）为25.7。28.5%（172/604）的患者完全减瘤（CCR 0/1）。3~4级不良事件发生率为21.7%（131/604），围手术期死亡率为0.7%（4/604），术后5年生存率为53.6%。高级别病理类型、不完全减瘤（CCR 2/3）、PCI>20、3~4级不良事件是PMP患者预后不良的独立危险因素。   结论   阑尾源性PMP临床罕见，治疗方法特殊，对于怀疑或确诊PMP的患者，尽早行规范CRS+HIPEC治疗，有望取得良好的预后。      

细胞减灭术联合腹腔热灌注化疗治疗恶性腹膜间皮瘤20例分析

  目的  探讨肿瘤细胞减灭术（cytoreductive surgery,CRS）联合腹腔热灌注化疗（hyperthermic intraperitoneal chemotherapy,HIPEC）治疗恶性腹膜间皮瘤（malignant peritoneal mesothelioma,MPM）的围手术期安全性及其疗效。  方法  回顾性分析2015年1月至2020年6月于航天中心医院接受治疗的20例MPM患者的临床病理资料,评价CRS+HIPEC治疗模式安全性,通过单因素及多因素统计分析研究影响患者生存的预后因素。  结果  20例患者中男性8例,女性12例,男女比例为:1:1.5。病理结果均为MPM,病理分型为上皮型。接受CRS+HIPEC治疗后总体1、2、3年生存率分别为73.9%、58.2%和43.6%,其中肿瘤细胞减灭程度（completeness of cytoreduction,CC）达到0/1的患者3年生存率为75%。单因素分析结果显示,性别（P=0.295）,CA125异常（P=0.256）,既往手术（P=0.460）以及静脉化疗（P=0.283）未见对总生存有显著影响。而年龄 > 60岁（P=0.037）,CC-2/3（P=0.027）,腹膜癌指数（peritoneal cancer index,PCI）≥20分（P=0.014）为预后不良的危险因素。  结论  MPM是一种罕见疾病,早期诊断困难,传统治疗预后差,静脉化疗无法有效改善预后。尽早行CRS+HIPEC综合治疗安全可靠,可以明显延长患者生存。      

细胞减灭术加腹腔热灌注化疗治疗结直肠癌腹膜转移癌病例对照研究

  目的  分析细胞减灭术（CRS）加术中腹腔热灌注化疗术（HIPEC）对结直肠癌腹膜转移癌的疗效及安全性。  方法  课题设计为回顾性病例对照研究, 收集结直肠癌腹膜转移癌（CRC PC）患者资料, 按临床病理参数匹配原则, 分为CRS组（CRS+术后全身化疗）29例, HIPEC组（CRS+HIPEC+术后全身化疗）33例。分析两组的总体生存期（OS）及严重不良事件（SAE）。  结果  两组患者临床病理学特征均衡可比, 术中PCI评分及器官/腹膜切除情况相似。两组中位随访时间分别为41.9个月（6.5~110.0个月）和32.0个月（10.5~95.9个月）, OS分别为8.5个月（95% CI: 4.9~12.1个月）和14.5个月（95% CI: 11.9~17.1月）（P=0.007）。术后30天内CRS组3例发生SAE, HIPEC组9例（P=0.126）。多因素分析显示, HIPEC、CC 0~1分、术后化疗周期≥6个周期为改善生存的独立预后因素。  结论  CRS+HIPEC可改善CRCPC患者生存期, SAE无显著增加, 安全性可接受。      

德国胃癌腹膜转移腹腔热灌注化疗的实践和进展

本文系统介绍了德国胃癌腹膜转移治疗和预防方面的临床试验结果和治疗经验。肿瘤细胞减灭术（cytoreductive surgery，CRS）联合腹腔热灌注化疗（hyperthermic intraperitoneal chemotherapy，HIPEC）和（或）胃切除术可以在有潜在治愈性的情况下实施，但仅能在经验丰富的中心并根据多学科诊疗团队的临床决策开展。目前，德国正在进行有关CRS+HIPEC治疗胃癌腹膜转移的有效性和安全性的高质量临床试验，也进行着有关胃癌切除术后辅助HIPEC治疗的临床试验。德国发明的加压腹腔气溶胶化疗（pressurized intraperitoneal aerosol chemotherapy，PIPAC）技术联合系统性化疗可作为姑息性治疗手段处理及预防腹水等并发症，期待有更多临床研究结果证实其有效性。      

德国胃癌腹膜转移腹腔热灌注化疗的实践和进展

本文系统介绍了德国胃癌腹膜转移治疗和预防方面的临床试验结果和治疗经验。肿瘤细胞减灭术（cytoreductive surgery，CRS）联合腹腔热灌注化疗（hyperthermic intraperitoneal chemotherapy，HIPEC）和（或）胃切除术可以在有潜在治愈性的情况下实施，但仅能在经验丰富的中心并根据多学科诊疗团队的临床决策开展。目前，德国正在进行有关CRS+HIPEC治疗胃癌腹膜转移的有效性和安全性的高质量临床试验，也进行着有关胃癌切除术后辅助HIPEC治疗的临床试验。德国发明的加压腹腔气溶胶化疗（pressurized intraperitoneal aerosol chemotherapy，PIPAC）技术联合系统性化疗可作为姑息性治疗手段处理及预防腹水等并发症，期待有更多临床研究结果证实其有效性。      

法国CRS+HIPEC治疗腹膜表面恶性肿瘤的经验

近30年来，腹膜癌的治疗取得了快速发展，部分病例接受肿瘤细胞减灭术（cytoreductive surgery，CRS）加腹腔热灌注化疗（hyperthermic intraperitoneal chemotherapy，HIPEC），可获长期生存，甚至临床治愈。法国在这一领域作出了历史性贡献，积极推动国际合作。本文主要介绍法国罕见病协作网（RENAPE和BIG-RENAPE）的发展壮大过程，在腹膜肿瘤学领域取得的历史性成就，在新时代所面临的机遇和挑战，包括腹膜肿瘤发生、发展的分子机制、分子病理诊断、腹膜转移的高危因素、CRS+HIPEC的适应证等，需要法国和全球腹膜表面恶性肿瘤领域学者共同面对新时代的机遇和挑战。      

细胞减灭术加腹腔热灌注化疗治疗胃癌腹膜转移癌的临床研究

  目的   分析细胞减灭术（Cytoreductive surgery,CRS）加腹腔热灌注化疗（Hyperthermic intraperitoneal chemotherapy,HIPEC）治疗胃癌腹膜癌（Peritoneal carcinomatosis,PC）的疗效和安全性。   方法  对106例胃癌PC患者随机分为CRS组或CRS+ HIPEC组,前者行常规手术治疗,后者行CRS+HIPEC,药物为羟基喜素碱（HTPC）20 mg加丝裂霉素（MMC）30 mg,或多西他赛120 mg加顺铂120 mg,溶于生理盐水12 L,温度（43±0.5）℃,时间60~90 min。主要终点指标为总体生存期,次要终点指标为安全性。   结果  入组患者106例,CRS组45例,CRS+HIPEC组61例,两组的主要临床病理指标平衡。至患者的中位随访期30个月时,胃癌PC相关死亡率在CRS组为93.3%（42/45）,CRS+HIPEC组为77.0%（47/61,P < 0.05）。两组患者的中位生存期在CRS组是7.0个月（95%CI:5.8~8.2个月）,CRS+HIPEC组是11.1个月（95% CI:8.3~13.9个月,P=0.003）。治疗相关的严重不良事件在CRS组为6例,CRS+HIPEC组为8例（P>0.05）。多因素分析显示CRS+HIPEC治疗、胃癌同时性PC患者、肉眼可见完全肿瘤细胞减灭、不发生严重不良事件、系统性化疗6个周期以上为影响预后的独立参数。   结论  对于胃癌同时性PC患者,CRS+HIPEC可延长生存期,并不明显增加严重不良事件。      

细胞减灭术加腹腔热灌注化疗治疗复发性卵巢癌

摘 要：［目的］ 研究细胞减灭术（CRS）加术中腹腔热灌注化疗（HIPEC）治疗复发性卵巢癌的疗效及安全性。［方法］ 回顾性分析59例复发性上皮性卵巢癌患者的临床病理资料,研究组（CRS+HIPEC+术后辅助化疗）28例和对照组（CRS+术后辅助化疗）31例。主要终点指标为总生存期（OS）,次要指标为安全性。［结果］ 两组患者的临床病理特征均匹配,中位OS分别为30.0月（95%CI：25.3~34.8）和22.8月（95%CI：18.2~27.4）（P=0.029）。1年、3年、5年生存率分别为85.7%、46.4%、39.3%和71.0%、35.5%、25.8%。CRS+HIPEC组中,铂类敏感型和耐药型患者的中位OS分别为30.0月（95%CI：6.5~57.1）和31.8月（95%CI：25.5~34.5）（P =0.633）。两组患者均无围手术期死亡病例,严重不良事件的发生率分别为17.9%和9.7%。多因素分析显示CRS+HIPEC,CC0-1、术后化疗≥6个周期为改善生存的独立预后因素。［结论］ CRS+HIPEC可延长复发性卵巢癌患者的生存期,严重不良事件无明显增加,安全可行。     

Impact of Tumor Angiogenesis in Peritoneal Mesothelioma After Radical Cytoreduction and Hyperthermic Intraperitoneal Chemotherapy

Peritoneal mesothelioma is one of the peritoneal surface malignancies where long-term survival is a reality after cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). Tumor angiogenesis has been shown to be of prognostic significance on survival in mesothelioma. We investigated the impact of survival of patients with peritoneal mesothelioma following CRS and HIPEC to determine the impact of tumor angiogenesis on survival after this radical surgical treatment. Paraffin sections of 23 patients who were treated with CRS and HIPEC were retrieved for immunohistochemical analysis. The immunostaining was performed using monoclonal mouse anti-human antibodies (VEGF-C and CD31) on an autostainer (Autostainer Plus; Dako, Inc.). The intensity of the stains were quantified using the Image-Pro Plus (IPP) 4.5 (Media Cybernetics, Silver Spring, MD). VEGF expression and microvessel density (MVD) using CD31 staining were studied. The median survival was 94 months with a 3-year survival rate of 51%. There was no impact on patient’s age, sex, peritoneal cancer index, tumor histopathology and survival outcomes between patients with low or high MVD and VEGF expression. After CRS and HIPEC, our results demonstrate that the prognostic significance of tumor angiogenesis is negated, highlighting the potential importance of other co-contributory mechanisms in mesotheliomagenesis and undergoing radial treatment.     

Indikationen für das HIPEC-Verfahren

For decades, there was therapeutic nihilism regarding patients with peritoneal carcinomatosis or primary peritoneal tumors. Development of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemoperfusion (HIPEC) completely changed this attitude. Nowadays, CRS and HIPEC are standards of care for pseudomyxoma peritonei and peritoneal mesothelioma, and are frequently used in secondary peritoneal metastasis. This review article summarizes the currently available publications and results for the different tumor entities, and critically discusses the indications: patients with pseudomyxoma peritonei and peritoneal mesothelioma can be treated with curative intent in cases of complete CRS; they also benefit from incomplete resection and HIPEC. In colorectal cancer, CRS and HIPEC are recommended in patients with a peritoneal cancer index (PCI) < 20. Proactive second-look surgery and HIPEC enable curative control of peritoneal carcinomatosis in patients at a high risk of peritoneal recurrence. In gastric cancer, limited peritoneal metastasis might be treated with CRS and HIPEC in individual patients. Staging laparoscopy is mandatory and has a decisive role in therapy planning.     

Unresectable peritoneal metastasis treated by pressurized intraperitoneal aerosol chemotherapy (PIPAC) leading to cytoreductive surgery and hyperthermic intraperitoneal chemotherapy

BackgroundPIPAC is a recent method of intraperitoneal chemotherapy. The aim of this study was to describe the clinical characteristics of the patients who became amenable to CRS & HIPEC after PIPAC treatment.MethodsAll patients diagnosed with unresectable PM who became resectable throughout PIPAC treatment were included. Outcome criteria were adverse events following PIPAC procedure and rate of secondary CRS and HIPEC.ResultsFour hundred thirty-seven PIPAC were done in 146 consecutive patients. Among them, 26 patients (17.8%) who underwent 76 PIPAC were scheduled for CRS and HIPEC after reduction of the peritoneal burden. PM were from gastric, peritoneal mesothelioma, ovarian, colorectal and small bowel in 13, 7, 4, 1 and 1 patients, respectively. At the time of the first PIPAC, median age was 58.6 years (32–76.3). Median PCI was 16 (1–39). All patients had systemic chemotherapy in between PIPAC session. Median consecutive PIPAC procedure was 3 (1–8). Complications occurred in 3 PIPAC session (4%) and there was no major complication (CTCAE III or higher). Complete CRS and HIPEC was achieved in 21 patients of the 26 scheduled (14.4%). The remaining 5 patients were considered unresectable at the exploratory laparotomy. Among patients who underwent CRS and HIPEC, with median follow-up of 7 (1–26) months, 14 patients (66.7%) were alive without recurrence, 2 patients (9.5%) were alive with recurrence and 5 patients (23.8%) died.ConclusionsComplete CRS and HIPEC can be achieved in strictly selected patient with unresectable PM at diagnosis after repeated PIPAC session with palliative intent.     

Outcomes of cytoreductive surgery with hyperthermic intraperitoneal chemotherapy for peritoneal mesothelioma and predictors of survival

Background: Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) benefits selected patients with peritoneal mesothelioma. We present the outcomes of this treatment strategy in a UK peritoneal malignancy national referral centre.

Methods: Observational retrospective analysis of data prospectively collected in a dedicated peritoneal malignancy database between March 1998 and January 2016.

Results: Of 1586 patients treated for peritoneal malignancy, 76 (4.8%) underwent surgery for peritoneal mesothelioma. Median age was 49?years (range 21–73?years). 34 patients (45%) were female. Of the 76 patients, 39 (51%) had low grade histological subtypes (mostly multicystic mesothelioma), and 37 (49%) had diffuse malignant peritoneal mesothelioma (DMPM; mostly epithelioid mesothelioma). Complete cytoreduction was achieved in 52 patients (68%) and maximal tumour debulking (MTD) was performed in 20 patients (26%); the remaining 4 patients (5%) underwent a laparotomy with biopsy only. HIPEC was administered in 67 patients (88%). Median overall (OS) and disease-free survival (DFS) after CRS was 97.8 (80.2–115.4) and 58.8 (47.4–70.3) months, respectively. After complete cytoreduction, 100% overall survival was observed amongst patients with low-grade disease. Ki-67 proliferation index was significantly associated with survival outcomes after complete cytoreduction for DMPM and was an independent predictor of decreased survival.

Conclusion: With adequate patient selection (guided by histological classification and Ki-67 proliferation index) and complete cytoreduction with HIPEC, satisfactory outcomes can be achieved in selected patients with peritoneal mesothelioma.     

左肾黏液样小管状和梭形细胞癌1例并文献复习

目的:探讨肾黏液样小管状和梭形细胞癌患者的临床病理特征、治疗方法、疗效评价及预后。方法:回顾性分析我们收治的1例左肾黏液样小管状和梭形细胞癌患者的临床病理资料,并复习相关文献。患者女,54岁。因左侧腰部疼痛就诊,CT检查提示左肾下极见大小约44 mm×37 mm×31 mm团块样影。结果:行左肾部分切除术,术后病理诊断:左肾黏液样小管状和梭形细胞癌。免疫组化:肿瘤细胞P-CK（+）,EMA（+）,CD68（PGM1）（-）,CK7（+）,CAM5.2（-）,PAX-8（+）,CK20（-）,Inhibin-a（-）,RCC（-）,Vimentin（+）,CD10（-）。术后患者恢复良好,康复出院,随访至今未见复发及转移。结论:肾黏液样小管状和梭形细胞癌是一类罕见的肾细胞癌,恶性程度相对较低,预后相对较好,治疗方法目前主张手术治疗,但术后仍需注意规律随访。     

英国国家腹膜癌中心30年来对PSOGI的贡献

20世纪90年代之前，腹膜恶性肿瘤被认为是癌广泛转移的表现，缺乏理想治疗方法。之后，基于临床研究，国际肿瘤学界对此观念发生转变，认为部分经选择的病例，接受以肿瘤细胞减灭术（cytoreductive surgery，CRS）加腹腔热灌注化疗（hyperthermic intraperitoneal chemotherapy，HIPEC）为核心的综合治疗不但能够有效控制疾病进展，还有可能达到临床治愈。英国贝辛斯托克医院是最早开展腹膜肿瘤诊治和研究的中心之一，30余年来，在腹膜肿瘤的诊疗和国际腹膜表面恶性肿瘤学会（peritoneal surface oncology group international，PSOGI）的创立发展等领域均作出了历史性的贡献:1994年，贝辛斯托克医院在Paul H. Sugarbaker教授指导下开展了第1例CRS，目前每年完成CRS超过350例；1998年，贝辛斯托克医院主持召开了第1届PSOGI大会；建立多学科团队，发展和推广CRS+HIPEC治疗策略；制订腹膜假黏液瘤（pseudomyxoma peritonei，PMP）和恶性腹膜间皮瘤（malignant peritoneal mesothelioma，MPM）指南；开展联合CRS和多脏器移植治疗腹膜肿瘤等临床研究。贝辛斯托克是PSOGI的基础，也是PSOGI发展和延续的重要组成部分，并将取得更大进展和更为丰硕的研究成果。      

Peritoneales Mesotheliom – ein seltener Tumor der Bauchhöhle

Malignant neoplasms of the mesothelium of the peritoneum are termed primary malignant peritoneal mesotheliomas (MPM) and arise as the result of exposure to asbestos. They are approximately 10 times rarer than pleural mesotheliomas with an incidence rate in industrial countries of 0.5-3/million in males and 0.2-2/million in females. The diagnosis mostly occurs in the advanced stage. For the differential diagnosis of MPM a large range of other neoplasms must be excluded. In addition to peritoneal metastases there are special forms, such as well differentiated papillary mesothelioma (WDPM),“benign” multicystic mesothelioma of the peritoneum (BMMP) and adenomatoid tumor. Intraperitoneal chemotherapy is often used in combination with hyperthermia (hyperthermic intraperitoneal chemotherapy HIPEC) and tumor resection or cytoreductive surgery (CRS). Complete resection of multiple diffuse growth of a peritoneal mesothelioma, as for example in pleural mesothelioma, is generally not possible. Mesothelioma of the peritoneum is caused by asbestos and is a recognized occupational disease known under code number 4105. Detection of asbestos can be carried out on lung tissue.     

Current practices and barriers to referral for cytoreductive surgery and HIPEC among colorectal surgeons: A binational survey

IntroductionCytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) has gained traction for the management of peritoneal metastases. The number of specialist units globally offering CRS/HIPEC is increasing. The aim of this survey was to assess current practices and barriers to referral for CRS/HIPEC among colorectal surgeons in Australia and New Zealand (ANZ).Materials and methodsAn online questionnaire was emailed to members of the Colorectal Surgical Society of Australia and New Zealand (CSSANZ). The survey contained 3 sections: namely; demographics, referral patterns and clinical scenarios. Questions on referral patterns included number of peritoneal metastases patients seen per year and referred to a CRS/HIPEC unit, awareness of such a unit and distance from principle place of practice. Different pathologies referred were also explored, as well as investigations performed. Barriers to referral were also surveyed.ResultsThe response rate was 28% (83/296). Twenty-five percent received CRS training. Most surgeons (95%) were aware of a CRS/HIPEC unit and had referred to one previously. Thirty-nine percent would refer all patients. Provision of good service and/or relationship with CRS/HIPEC specialist were the main reasons for referring to the nearest unit, followed by accessibility. Major factors preventing referral included extent of peritoneal disease (48%), patient characteristics and comorbidities (44%) and lack of evidence (20%). The most common pathologies referred included colorectal and appendiceal peritoneal metastases and pseudomyxoma peritonei.ConclusionColorectal specialist awareness of CRS/HIPEC units and accessibility is high. Strategies to improve referring physician/surgeon knowledge on patient selection and indications for CRS/HIPEC should be investigated and instituted to ensure all appropriate patients are referred to specialist units for discussion of suitability.