Patient Selection for Hyperthermic Intraperitoneal Chemotherapy in Patients With Colorectal Cancer: Consensus on Decision Making Among International Experts

BackgroundColorectal cancer (CRC) treatment for patients with peritoneal metastases is complex. The use of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) has continued to be debated. The aim of the present study was to assess the consensus among international experts for decision-making regarding the use of CRS and HIPEC for patients with CRC.Materials and MethodsOf 15 experts invited, 12 had provided their decision algorithms for CRS and HIPEC for patients with, or at high risk of, peritoneal metastases from CRC. Using the objective consensus method, the results were transformed into decision trees to provide information on the consensus and discordance.ResultsOnly 1 scenario was found for which the consensus on performing HIPEC had reached 100%. The scenario was the treatment of young patients with complete cytoreduction and a peritoneal carcinomatosis index (PCI) of < 16 in the presence of certain risk factors. Five major decision criteria were identified: age, PCI, completeness of cytoreduction, extent of extraperitoneal metastases (EoMs), and, in the case of unverified EoMs, additional risk factors. Consensus was found regarding refraining from using HIPEC for older patients with a high PCI. The consensus further increased when addressing incomplete cytoreduction and an extensive extent of EoMs.ConclusionA definite consensus concerning the use of HIPEC was only determined for very selected scenarios. These findings can be used for general guidance; however, owing to the heterogeneity of each individual situation, the impracticality of presenting the information through decision trees, and the unclear future of the role of HIPEC in the adjuvant setting, a one-on-one transfer to daily clinical practice could not be achieved.     

Myosteatosis and myofibrosis: Relationship with aging,inflammation and insulin resistance

The mechanisms impairing muscle quality and leading to myofibrosis (MF) and myosteatosis (MS) are incompletely known. In biopsies of paraspinous muscle (PM) of 16 elderly men undergoing elective vertebral surgery, we histologically determined the area of MF and MS expressed as muscle quality index (MQI), in order to investigate the relation between them, as well as the main predictors of muscle quality. Total PM area and intermuscular adipose tissue (IMAT) were evaluated by MRI and body composition by DXA. Circulating fasting glucose, insulin, hs-CRP, leptin, adiponectin and IL-6 were measured and HOMA index calculated. Quantification of gene expression in PM and in subcutaneous adipose tissue (SAT) overlying the muscle was performed by rt-PCR. The degree of MS and MF was significantly and positively related to each other and positively associated with BMI, waist, FM and FM% as well as with IMAT. The area of PM was negatively related with MF even after adjustment for weight. Leptin was positively associated with MF and MS, whereas hs-CRP to MF. In backward regression analyses, larger waist and smaller PM area explained 90% of MF variance, whereas leptin about 80% of MS variance. IL-6 expression in SAT was significantly higher in participants with higher MQI values. In PM biopsies we found significantly higher expression of SOCS-3 and a trend toward higher expression of myostatin with greater degrees of MQI. MS and MF are related phenomena that concur to alter muscle quality and both should be considered in further studies on the evolution of sarcopenia.     

循环热灌注大剂量顺铂治疗胃肠道肿瘤腹水的疗效分析

目的比较循环热灌注大剂量顺铂与单纯灌注化疗治疗胃肠道肿瘤腹水的近期疗效及并发症。方法同期胃肠道肿瘤腹水患者103例,随机分为两组,观察组通过腹腔内穿刺置双管建立循环双通路,先缓慢放出腹腔积液,再行循环热灌注。并于灌注液中加入大剂量顺铂,治疗结束后腹腔内存留1000～1500mL灌注液;对照组置腹腔引流管,先予腹腔放液,后灌注1000mL加有大剂量顺铂的液体,24h后放出液体。两个疗程后对其疗效及副反应进行比较。结果两组103例患者两个疗程后全部可评价疗效,观察组有效率为90．7％,明显高于对照组的51．0％,两组间差异有高度统计学意义（P〈0．01）,毒副反应均较轻微,两组间差异无统计学意义（P〉0．05）。结论循环热灌注大剂量顺铂治疗胃肠道肿瘤腹水安全、微创．不良反应少而轻．近期疗效明显。     

125I粒子与缓释化疗粒子联合应用靶向治疗复发性直肠癌

目的 探讨应用放、化疗粒子联合植入法综合治疗复发性直肠癌的可行性、安全性及短期疗效。方法 自2001年12月至2005年12月,应用放、化疗粒子联合植入法综合治疗复发性直肠癌26例,均为直肠癌Mile＇s术后盆腔复发病人。在治疗计划指导下,交替植入氟尿嘧啶缓释化疗粒子和放射性125I粒子。放射性粒子的肿瘤匹配周边剂量（matched peripheral dose,MPD）为90～130Gy。平均每例使用^125Ⅰ粒子12粒,氟尿嘧啶600 mg。结果 26例病人手术均顺利完成,未发生出血、感染等并发症,经盆腔摄片证实放射性粒子的位置无变化。疼痛缓解率为88.9%（16/18）,平均疼痛缓解时间为5～10 d。于术后3～6个月CT复查肿瘤变化,提示瘤体不同程度缩小,其中2例完全缓解,19例部分缓解,4例稳定,局部控制率为81%。随访6～42个月,中位生存期为29个月,最长1例随访时间为术后42个月,现仍存活。1例术后6个月死于全身广泛转移。结论 放射性125I粒子和氟尿嘧啶缓释化疗粒子联合应用局部植入技术具有安全、微创及并发症发生率低的特点,是综合治疗复发性直肠癌较有效的手段之一。     

The GLIM criteria as an effective tool for survival prediction in gastric cancer patients

BackgroundThe Global Leadership Initiative on Malnutrition released a new version of the malnutrition criteria (GLIM criteria). To investigate the influence of the GLIM criteria on the long-term efficacy of radical gastric cancer surgery and establish a nomogram to predict the long-term prognosis of patients with gastric cancer.MethodsA retrospective analysis of 1121 patients with gastric cancer in our department from 2010 to 2013 was performed. A nomogram was established to predict overall survival (OS) based on the GLIM criteria. Patients were divided into the low-risk group (LRG) and high-risk group (HRG) based on the established nomogram.ResultsMultivariate Cox regression analyses showed that GLIM criteria was an independent risk factor for the 5-year OS (HR = 1.768, Cl:1.341–2.329, p < 0.001). The C index, AUC and Time-ROC of the nomogram were significantly better than that of GLIM criteria and traditional criteria. The 5-year OS of patients receiving adjuvant chemotherapy in the high-risk group was significantly higher than that of patients without chemotherapy (45.77% vs. 24.73%,p < 0.001).ConclusionsThe GLIM criteria independently influence the long-term outcome of patients after radical gastric cancer surgery. The established nomogram can predict the long-term survival of patients with gastric cancer, and postoperative adjuvant chemotherapy for HRG can significantly improve the 5-year OS of patients.     

Current status and future prospects of clinical trials on CRS + HIPEC for gastric cancer peritoneal metastases

Abstract

Purpose: There is no standard treatment for peritoneal metastases (PM) from gastric cancer (GC). The aim of this review is to evaluate the clinical trials on cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) for GC PM.

Materials and methods: The published clinical trials on CRS?+?HIPEC for GC PM are critically evaluated, and survival and safety are the primary endpoints. In addition, the registered ongoing clinical trials are summarised.

Results: The natural course of GC PM is <5 months. CRS?+?HIPEC could improve the overall survival (OS). In prospective studies, the median OS was 11.0 months in the CRS?+?HIPEC group vs. 5.4 months in the CRS alone group. In case-control studies, the median OS was 13.3 months in the CRS?+?HIPEC group vs. 7.9 months in the CRS alone group. In cohort studies, the median OS after CRS?+?HIPEC was 13.3. The median 1-, 2- and 5-year survival rates after CRS?+?HIPEC were 50.0%, 35.8% and 13.0%, respectively. There is no statistically significant increase in serious adverse events that are directly attributed to CRS?+?HIPEC.

Conclusions: The combination of CRS and HIPEC is a promising integrated treatment strategy for GC PM that has encouraging initial results, calling for urgent further evaluation of this strategy in randomised control trials (RCTs).     

Gsα蛋白与腹膜假黏液瘤临床病理特征及预后的相关性研究

  目的  探讨鸟苷酸结合蛋白α亚基（guanine nucleotide binding protein alpha subunit,Gsα）表达与腹膜假黏液瘤（pseudomyxoma peritonei,PMP）主要临床病理特征及预后的相关性。  方法  收集首都医科大学附属北京世纪坛医院65例PMP患者病理标本,行常规组织病理学和定量免疫组织化学检测Gsα蛋白表达,研究Gsα蛋白表达与主要临床病理特征及预后的相关性。  结果  65例PMP肿瘤行定量免疫组织化学分析,Gsα高表达者35例（53.8%）,低表达者30例（46.2%）。单因素分析显示,Gsα高表达与下列5个临床病理指标呈正相关:术前肿瘤标志物（χ2=3.68,P=0.087）、术中腹水量（χ2=3.69,P=0.055）、腹膜癌指数评分（peritoneal cancer index,PCI）（χ2=3.12,P=0.077）、肿瘤细胞减灭程度评分（completeness of cytoreduction,CC）（χ2=2.72,P=0.099）、组织病理分级（χ2= 5.85,P=0.016）。多因素分析显示,Gsα蛋白高表达仅与组织病理分级呈独立正相关:高级别或高级别伴印戒细胞的组织病理类型（OR=3.47,95%CI:1.1 ～ 15.6,P=0.029）。Cox多因素分析显示,年龄（HR=8.08,95%CI:2.42 ～ 26.97,P=0.001）、既往手术（HR=0.24,95%CI:0.07 ～ 0.81,P=0.022）、组织病理分级（HR=3.92,95%CI:1.12 ～ 13.70,P=0.032）;Gsα蛋白表达（HR=3.25,95%CI:1.01 ～ 10.5,P=0.048）为独立预后因素。  结论  Gsα蛋白高表达与高级别或高级别伴印戒细胞的组织病理类型呈正相关,提示PMP预后不良。