Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in treatment of gastric cancer with peritoneal carcinomatosis

Although gastric cancer with peritoneal carcinomatosis is associated with poor prognosis and is generally treated with palliative systemic therapy,recent studies have shown that cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) may prove to be an efficacious treatnent option.In addition to reviewing the natural history of gastric cancer with peritoneal carcinomatosis,this mini-review examines literature on the efficacy of CRS and HIPEC as compared to chemotherapy and surgical options.Both randomized and nonrandomized studies were summarized with the emphasis focused on overall survival.In summary,CRS and HIPEC are indeed a promising treatment option for gastric cancer with peritoneal carcinomatosis and large randomized clinical trials are warranted.     

减瘤术联合术中腹腔内温热化疗治疗消化道肿瘤腹膜转移

消化道恶性肿瘤腹膜转移在临床十分常见,预后极差。近年来,减瘤术联合术中腹腔内温热化疗方案治疗效果满意。现综述如下。     

Cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy improves survival of patients with peritoneal carcinomatosis from colorectal cancer: A case‐control study from a Chinese center

Background

Advanced colorectal cancer (CRC) is prone to developing peritoneal carcinomatosis (PC). This case‐control study was to compare the efficacy and safety of cytoreductive surgery (CRS) versus CRS plus hyperthermic intraperitoneal chemotherapy (HIPEC) in Chinese patients with CRC PC.

Methods

The 62 consecutive PC patients were treated with CRS (Control group, n = 29) or CRS + HIPEC (Study group, n = 33). The primary end point was overall survival (OS), the secondary end points were perioperative safety profiles.

Results

For the comparison of Control versus Study groups, the peritoneal cancer index (PCI) ≤20 was 13 (44.8%) versus 16 (48.5%) patients (P = 0.78), complete cytoreduction (CC0‐1) was achieved in 9 (31.0%) versus 14 (42.4%) cases (P = 0.36). At the median OS was 8.5 (95% confidence interval [CI] 4.7–12.4) versus 13.7 (95% CI 10.0–16.5) months (P = 0.02), the 1‐, 2‐, and 3‐year survival rates were 27.5% versus 63.6%, 12.0% versus 20.0%, and 0.0% versus 16.0%, respectively. Serious adverse events in postoperative 30 days were 9.4% versus 28.6% (P = 0.11). Multivariate analysis revealed that CRS + HIPEC, CC0‐1, adjuvant chemotherapy ≥6 cycles were independent factors for OS benefit.

Conclusion

CRS + HIPEC could improve OS for CRC PC patients, with acceptable perioperative safety. J. Surg. Oncol 2014; 109:730–739. © 2013 The Authors. Journal of Surgical Oncology. Published by Wiley Periodicals, Inc.     

Cytoreductive surgery in combination with hyperthermic intraperitoneal chemotherapy improves survival in patients with colorectal peritoneal metastases compared with systemic chemotherapy alone

Background:

Colorectal cancer peritoneal metastasis (CPM) confers an exceptionally poor prognosis, and traditional treatment involving systemic chemotherapy (SC) is largely ineffective. Cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) is increasingly advocated for selected patients with CPM; however, opinions are divided because of the perceived lack of evidence, high morbidity, mortality, and associated costs for this approach. As there is no clear consensus, the aim of this study was to compare outcomes following CRS+HIPEC vs SC alone for CPM using meta-analytical methodology, focusing on survival outcomes. Secondary outcomes assessed included morbidity, mortality, quality of life (QOL), and health economics (HE).

Methods:

An electronic literature search was conducted to identify studies comparing survival following CRS+HIPEC vs SC for CPM. The odds ratio (OR) was calculated using the Mantel–Haenszel method with corresponding 95% confidence intervals (CI) and P-values. Heterogeneity was examined using the Q-statistic and quantified with I². The fixed-effect model (FEM) was used in the absence of significant heterogeneity. For included studies, 2- and 5-year survival was compared for CRS+HIPEC vs SC alone.

Results:

Four studies (three case–control, one RCT) provided comparative survival data for patients undergoing CRS+HIPEC (n=187) vs SC (n=155) for CPM. Pooled analysis demonstrated superior 2-year (OR 2.78; 95% CI 1.72–4.51; P=0.001) and 5-year (OR 4.07; 95% CI 2.17–7.64; P=0.001) survival with CRS+HIPEC compared with SC. Mortality ranged from 0 to 8%. No data were available for the assessment of QOL or HE.

Conclusions:

Although limited by between-study heterogeneity, the data support the assertion that in carefully selected patients, multimodal treatment of CPM with CRS+HIPEC has a highly positive prognostic impact on medium- and long-term survival compared with SC alone. There is a paucity of comparative data available on morbidity, QOL, and HE.     

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for peritoneal carcinomatosis from colorectal and gastrointestinal origin shows acceptable morbidity and high survival

Background

Peritoneal carcinomatosis from colorectal origin carries a poor prognosis. Recent clinical studies show that cytoreductive surgery (CS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) improves survival of selected patients with a colorectal carcinoma and isolated peritoneal carcinomatosis in the absence of extra-abdominal metastases. Here, we report the clinical outcomes and survival after cytoreductive surgery and HIPEC of the first cohort of patients treated in our institution.

Methods

Sixty-seven patients underwent a laparotomy. Complete cytoreduction could be performed in 49 patients, who underwent a total of 53 CS–HIPEC procedures. All had peritoneal carcinomatosis originating from primary colorectal, cecal, appendiceal, and gastric tumors.

Results

In patients who underwent CS–HIPEC, an R0 resection could be achieved in 4%, R1 in 88%, and R2 in 8%. The 30-day mortality was 0; one patient died in-hospital after 10 weeks. The median hospital stay was 12 days (range 4–56). The overall morbidity was 43%, including extended gastroparesis (11%), anastomotic failure (11%) and intra-abdominal abscess (9%). Mean time to clinical recurrence was 12 months (range 4–22). The actuarial 1-year survival was 88% and 2-year survival was 75%.

Conclusion

In well-selected patients referred to a specialized institution, CS–HIPEC has an accep table morbidity and high survival rate.     

Toward curative treatment of peritoneal carcinomatosis from nonovarian origin by cytoreductive surgery combined with perioperative intraperitoneal chemotherapy

BACKGROUND:

Peritoneal carcinomatosis (PC) from nonovarian malignancies long has been regarded as a terminal disease. Over the past decade, new locoregional therapeutic approaches combining cytoreductive surgery with perioperative intraperitoneal chemotherapy (PIC) have evolved that have demonstrated improved survival.

METHODS:

A retrospective, multicenter cohort study was performed in French‐speaking institutions to evaluate toxicity and principal prognostic factors after cytoreductive surgery and PIC (hyperthermic intraperitoneal chemotherapy [HIPEC] and/or early postoperative intraperitoneal chemotherapy [EPIC]) for PC from nongynecologic malignancies.

RESULTS:

The study included 1290 patients from 25 institutions who underwent 1344 procedures between February 1989 and December 2007. HIPEC was performed in 1154 procedures. The principal origins of PC were colorectal adenocarcinoma (N = 523), pseudomyxoma peritonei (N = 301), gastric adenocarcinoma (N = 159), peritoneal mesothelioma (N = 88), and appendiceal adenocarcinoma (N = 50). The overall morbidity and mortality rates were 33.6% and 4.1%, respectively. In multivariate analysis, patient age, the extent of PC, and institutional experience had a significant influence on toxicity. The overall median survival was 34 months; and the median survival was 30 months for patients with colorectal PC, not reached for patients with pseudomyxoma peritonei, 9 months for patients with gastric PC, 41 months for patients with peritoneal mesothelioma, and 77 months for patients with PC from appendiceal adenocarcinoma. Independent prognostic indicators in multivariate analysis were institution, origin of PC, completeness of cytoreductive surgery, extent of carcinomatosis, and lymph node involvement.

CONCLUSIONS:

A therapeutic approach that combined cytoreductive surgery with PIC was able to achieve long‐term survival in a selected group of patients who had PC of nonovarian origin and had acceptable morbidity and mortality. The current results indicated that this treatment should be centralized to institutions with expertise in the management of PC. Cancer 2010. © 2010 American Cancer Society.     

Cytoreductive surgery and intraperitoneal hyperthermic chemotherapy for peritoneal carcinomatosis from small bowel adenocarcinoma

INTRODUCTION: Peritoneal carcinomatosis (PC) is associated with a dismal prognosis. Small bowel adenocarcinoma is a rare etiology for PC. Due to the rarity, poor prognosis, and lack of standard treatment, we chose to review our experience with this disease process treated with cytoreductive surgery (CS) and intraperitoneal hyperthermic chemotherapy (IPHC). METHODS: From a prospective database of IPHC patients, six patients diagnosed with PC from adenocarcinoma of the small bowel were identified. Between 1995 and 2004 these patients underwent CS and IPHC with Mitomycin C. A retrospective review was performed on these patients with mortality as the primary outcome measure. RESULTS: Three of the six patients in this series are still alive, with a mean follow-up of 19.7 months after treatment with CS and IPHC. Three patients died of disease progression 29, 30, and 45 months after IPHC. Median survival after diagnosis of small bowel adenocarcinoma was 54 months, while median survival after CS and IPHC for PC was 30.1 months. CONCLUSIONS: Small bowel adenocarcinoma with PC remains an unusual therapeutic challenge. Treatment with CS and IPHC is an attractive option for patients in this setting.     

Intraperitoneal chemotherapy as adjuvant treatment to prevent peritoneal carcinomatosis of colorectal cancer origin: a systematic review

Background:

Peritoneal carcinomatosis (PC) of colorectal cancer (CRC) origin is associated with poor outcome. This systematic review evaluates the available evidence about adjuvant (hyperthermic) intraperitoneal chemotherapy ((H)IPEC) to prevent the development of PC.

Methods:

A systematic search of literature was conducted in August 2013 in PubMed, Embase, and the Cochrane database for studies on (H)IPEC to prevent PC in patients who underwent curative surgery for primary CRC.

Results:

Seven comparative studies and five cohort studies were selected. Treatment schedules varied between repeated fluoropyrimidine-based IPEC administration in the ambulatory setting to intra-operative (H)IPEC procedures using mitomycin-C or oxaliplatin. The reported rates of major complications related to adjuvant (H)IPEC was low. Four out of five evaluable comparative studies reported a significant difference in the incidence of PC in favour of (H)IPEC. All three comparative studies reporting on survival after intra-operative (H)IPEC showed a significant survival benefit in favour of the experimental arm. Substantial heterogeneity in patient selection, treatment protocols, and treatment effect evaluation among studies was observed.

Conclusions:

The currently available evidence about adjuvant (H)IPEC in high-risk CRC is limited and subject to bias, but points towards improved oncological outcome and supports further randomised studies.     

肿瘤细胞减灭加腹腔热灌注化疗术后静脉血栓栓塞症的预防

  目的  评估行肿瘤细胞减灭术（cytoreductive surgery,CRS）加腹腔热灌注化疗（hyperthermic intraperitoneal chemotherapy,HIPEC）治疗的腹膜癌患者静脉血栓栓塞症（venous thromboembolism,VTE）发生风险,研究术后早期主/被动活动联合间歇充气加压按摩对VTE的预防效果。  方法  对2015年5月至2016年8月武汉大学中南医院肿瘤科收治的120例胃肠道及妇科肿瘤等来源的腹膜癌患者行CRS+HIPEC治疗,使用Caprini血栓风险评估模型评价VTE风险,所有患者采取早期肢体主/被动活动及间歇充气加压按摩治疗,记录分析VTE相关事件。  结果  患者中位Carprini评分为12（10~16）分,均为VTE极高危组,在3个月的随访中仅1例患者发生深静脉血栓,经药物治疗后痊愈。  结论  腹膜癌患者VTE风险极高,术后早期足背曲/跖曲及扩胸等主/被动运动联合间歇充气加压按摩,可有效预防VTE。      

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for colorectal cancer: survival outcomes and patient selection

Background

Chemotherapy hyperthermic intraperitoneal chemotherapy (HIPEC) is playing an ever increasing role in the management of colorectal cancer (CRC) with peritoneal metastases (PM) as results approach those of surgical resection of liver metastases. Selection criteria for treatment type, sequence and timing of currently available therapies remain ill-defined.

Methods

We review the current published literature analyzing outcomes by treatments with surgery, systemic chemotherapy, cytoreductive surgery (CRS) and HIPEC, and ongoing clinical trials. A clinical pathway that incorporates all currently available therapies, determining the timing and sequence of such therapies was constructed.

Results

Most of the literature on outcome data comes from studies reporting the results of CRS and HIPEC with large series showing a median survival of 32-47 months. Meanwhile, the vast majority of patients, over 90% in the United States, are being treated with palliative systemic therapies following the NCCN guidelines.

Conclusions

Cooperation between medical and surgical oncologists represents an unmet need in oncology when it comes to patients with CRC with PM. The presented clinical pathway constitutes a feasible and much needed first step to start this cooperation.     

细胞减灭术联合腹腔热灌注化疗治疗胃癌腹膜转移的系统评价

目的:系统评价细胞减灭术(cytoreductive surgery,CRS)联合腹腔热灌注化疗(hyperthermic intraperitoneal chemotherapy,HIPEC)治疗胃癌伴腹膜转移患者的临床有效性和安全性,为临床应用与深入研究提供参考.方法:计算机检索PubMed、Cochrane图书馆、EMbase、MEDLINE(Ovid)、CNKI、维普中刊数据库、中国生物医学文献数据库,收集利用CRS联合HIPEC治疗胃癌伴腹膜转移患者的所有研究,包括随机对照试验(randomized controlled trail,RCT)和非随机对照试验(non-randomized controlled trail,非RCT),对纳入研究主要从生存期和安全性两方面进行统计分析.结果:纳入1项RCT和8项非RCT,共504例患者.生存期方面,RCT中,CRS联合HIPEC组的中位生存期为11个月,明显高于单纯CRS组的7个月(P=0.003).8项非RCT中,CRS联合HIPEC治疗的1、2、3年合计总体生存率分别为52.9%、27.1%、16.8%.手术切除程度达到CC 0~1分是预后较好的预测指标.安全性方面,非RCT显示联合治疗方案围手术期总体死亡率为4.8%,严重并发症的合计发生率为24.9%,在RCT中这两项数据分别为0和13.1%.结论:对于胃癌伴腹膜转移,尤其是达到CC 0~1切除的患者,CRS联合HIPEC能延长患者的生存期,但同时存在较高的严重并发症发生率.     

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。      

细胞减灭术联合腹腔热灌注化疗治疗腹膜癌的围术期规范化护理

目的：探讨如何对细胞减灭术联合腹腔热灌注化疗治疗后的腹膜癌患者进行规范围术期护理。方法对33例腹膜癌患者的围术期护理进行回顾性分析,对护理的具体内容、围术期的不良事件进行总结规范。结果规范的护理减少了围术期不良事件的发生,促进了腹腔化疗管路的改进。结论针对细胞减灭术联合腹腔热灌注化疗治疗腹膜癌的患者进行规范的围术期护理,能够减少围术期不良事件的发生。