Prophylactic hyperthermic intraperitoneal chemotherapy in patients with epithelial appendiceal neoplasms

Background Prophylactic hyperthermic intraperitoneal chemotherapy (HIPEC) is a promising approach for preventing peritoneal carcinomatosis in high-risk patients. We report our initial experience with prophylactic HIPEC in a series of patients with appendiceal neoplasms. Methods We retrospectively reviewed our prospectively maintained database to identify patients who underwent HIPEC in the absence of peritoneal disease. Patients with previously documented peritoneal surface disease were excluded. Data regarding clinical, operative and pathological features were analysed. Results Out of 322 HIPEC procedures performed between March 2007and August 2015, we identified 16 patients who underwent surgery with prophylactic intent. Primary diagnoses included high-grade and low-grade appendiceal neoplasms. Most patients presented originally with appendiceal perforation; all patients underwent initial surgery during which the appendix or right colon were resected. Following a median time interval of 2.2 months, a second surgery performed at our institution consisted of completion of omentectomy, partial colectomy and oophorectomy, with administration of prophylactic HIPEC (using mitomycin C). A totally laparoscopic approach was attempted and achieved in 11 patients in whom the median duration of surgery, estimated intraoperative blood loss and length of hospitalisation were 251?min, 100?cm³ and 4 days, respectively. There were no cases of major perioperative morbidity or mortality. Conclusions Prophylactic HIPEC for appendiceal neoplasms is feasible, safe and may be performed laparoscopically. Larger studies with long-term follow-up are needed to determine whether a survival benefit is associated with this treatment.     

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.     

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。     

Guidelines on the use of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in patients with peritoneal surface malignancy arising from colorectal or appendiceal neoplasms

To meet the needs of patients, Canadian surgical and medical oncology leaders in the treatment of peritoneal surface malignancies (psms), together with patient representatives, formed the Canadian HIPEC Collaborative Group (chicg). The group is dedicated to standardizing and improving the treatment of psm in Canada so that access to treatment and, ultimately, the prognosis of Canadian patients with psm are improved.Patients with resectable psm arising from colorectal or appendiceal neoplasms should be reviewed by a multidisciplinary team including surgeons and medical oncologists with experience in treating patients with psm. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy should be offered to appropriately selected patients and performed at experienced centres.The aim of this publication is to present guidelines that we recommend be applied across the country for the treatment of psm.     

腹膜癌行肿瘤细胞减灭加腹腔热灌注化疗术后高肌红蛋白血症的治疗*

  目的  探讨腹膜癌患者接受肿瘤细胞减灭（cytoreductive surgery,CRS）联合腹腔热灌注化疗（hyperthermic intraperitoneal chemotherapy,HIPEC）术后血肌红蛋白（myoglobin,Mb）水平的变化及其临床意义。  方法  回顾性研究60例接受CRS+HIPEC的腹膜癌病例。患者术后均出现高肌红蛋白血症,给予碳酸氢钠静脉输注及补液治疗。测定手术前后Mb、尿素氮、肌酐的浓度变化。  结果  CRS+HIPEC术后Mb水平明显升高,手术当日即达到高峰（416.667±110.966）μg/L。静脉输注碳酸氢钠有助于降低Mb水平及潜在风险。Mb水平在术后3~4d下降至正常范围内。血尿素氮（BUN）水平在术后升高,在术后第4天达峰值。血钙（Cr）在术后2天开始下降。1例患者发展为肾功能不全,脓毒血症,术后第26天死亡。其他患者均恢复良好。  结论  CRS+HIPEC术后常出现高肌红蛋白血症,Mb是内环境不稳定的一个早期而敏感指标。静脉输注碳酸氢钠可迅速降低Mb水平,减轻主要脏器功能损害。      

Morbidity after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy with carboplatin used for ovarian,tubal, and primary peritoneal cancer

Background and objectives: Hypertherm intraperitoneal chemotherapy (HIPEC) is increasingly used in the treatment of ovarian, tubal, and primary peritoneal cancer (OC). The aim was to evaluate short-term morbidity of cytoreductive surgery (CRS) and carboplatin HIPEC. Methods: Prospective feasibility study performed from January 2016 to December 2017. Twenty-five patients with primary OC (FIGO III-IV) received upfront or interval CRS combined with carboplatin HIPEC at dose 800 mg/m ². Primary outcome measurements: grade 3 to 5 adverse events within 30 days according to Common Terminology Criteria for Adverse Events. Secondary outcome measurements: reoperation rate, length of hospital stay, readmission rate, and time from surgery to systemic chemotherapy administration. Results: No deaths (grade 5) or grade 4 adverse events were observed. Eleven patients (44.0%) experienced at least one grade 3 adverse event, the most common being an infection (28.0%) and neutropenia (12.0%). The reoperation rate was 8.0%. The median hospital stay was 14 days (range 9-25 days), and five patients (25.0%) were readmitted within 30 days after surgery. Median time from surgery to the administration of the first dose of systemic chemotherapy was 41 days (range 24-81 days). Conclusion: Our small-scale prospective study supports that CRS and carboplatin HIPEC used for primary advanced-stage OC is feasible with acceptable morbidity.     

Diagnostic and therapeutic laparoscopy in assessment and management of patients with appendiceal neoplasms

Introduction: Radiological imaging often underestimates the extent of low volume peritoneal disease. The benefit of laparoscopy in assessing peritoneal metastases from colorectal and gastric cancer is accepted, but is inconclusive for appendiceal malignancy. We report our experience of diagnostic (DL) and therapeutic laparoscopy (TL) in patients with appendiceal tumours to determine indications and role in assessment and management.

Methods: A retrospective review of a National Peritoneal Malignancy Centre’s prospectively maintained database was performed. All patients with appendiceal neoplasms who underwent DL or TL between September 2011 and January 2016 were included. The indications and outcomes of the laparoscopy, complications and interval to laparotomy were evaluated.

Results: Six hundred and eighty-five patients underwent surgery for appendiceal neoplasms during the study period, of which 73 (10.6%) underwent laparoscopy (50 DL, 23 TL). The main indications for DL were to clarify imaging and stage patients with high-risk histology. Indications for TL were an abnormal appendix without gross pseudomyxoma peritonei (PMP) or with low volume PMP, and concerns for fertility in the presence of PMP. DL resulted in 16 patients (32%) avoiding laparotomy because of extensive disease or no tumour found. Overall, 28 patients were assessed to have resectable disease and at laparotomy, 25/28 had complete cytoreduction with three patients unresectable. In the TL group, appendicectomy and peritoneal lavage was achieved in all four women with fertility concerns, allowing them to conceive thereafter. There were no complications.

Conclusions: Patients with high-risk appendiceal neoplasm may benefit from DL, and potentially avoid unnecessary laparotomy. TL is useful in patients with low volume PMP and may aid fertility in selected patients.     

Applications of hyperthermic intraperitoneal chemotherapy for metastatic colorectal cancer

Introduction: Cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) plays a pivotal role in the current treatment of peritoneal carcinomatosis (PC) from colorectal cancer (CRC). Since the first demonstration, benefits for patients and especially an increase in survival have been described. In recent years, feasibility, efficacy and safety of HIPEC have been improved and progress has been made in understanding its oncological mechanism.

Areas covered: In this article, leading publications have been reviewed including clinical trials to describe the clinical presentation of PC due to CRC and present recent evidence of the CRS/HIPEC procedure. The surgical approach including evaluation of the extent of PC is described and, in addition, the article reports about different HIPEC techniques as well as several protocols. Furthermore, the development and prognostic benefit of the combination of intraperitoneal and intravenous chemotherapy are outlined. Consideration has been given in particular to patient selection and the use of HIPEC if complete cytoreduction is not feasible.

Expert commentary: The CRS/HIPEC procedure represents a curative approach to treat patients with PC from CRC. However, surgical skills and the HIPEC technique still require specialized oncological centers.     

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.     

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.     

Modern systemic chemotherapy in surgically unresectable neoplasms of appendiceal origin

BACKGROUND:

Appendiceal neoplasms include tumors ranging from benign‐appearing cells with widespread mucin deposits to aggressive poorly differentiated signet ring cell adenocarcinomas. Traditionally, these tumors are treated with cytoreductive surgery followed by hyperthermic intraperitoneal chemotherapy. For some patients, cytoreductive surgery is not an option, and minimal published data exist in the management and outcome of these patients. A retrospective analysis was conducted to determine the benefit of modern systemic chemotherapy in patients with disseminated appendiceal neoplasm who were not considered optimal candidates for cytoreductive surgery.

METHODS:

A retrospective review was conducted using The University of Texas M. D. Anderson Cancer Center tumor registry between January 2000 and July 2005. Response was determined by radiographic response and/or overall clinical benefit.

RESULTS:

Of 186 patients diagnosed with appendiceal neoplasm, 54 (29%) patients considered to be suboptimal surgical candidates received ≥2 cycles of systemic chemotherapy. Thirty (55.6%) patients had a disease control rate noted as a complete response, partial response, or stable disease. After a median follow‐up of 24 months, the median progression‐free survival (PFS) and overall survival were determined to be 7.6 months (95% confidence interval [CI], 4‐11) and 56 months (95% CI, 36‐not applicable), respectively.

CONCLUSIONS:

Systemic chemotherapy has a role in appendiceal neoplasm patients who are suboptimal candidates for cytoreductive surgery. The intermediate PFS indicates the challenges that exist for appendiceal neoplasm patients in this setting. Prospective randomized trials including systemic chemotherapy are needed to provide further insight into this malignancy, for which no standard exists. Cancer 2010. © 2010 American Cancer Society.     

新辅助化疗联合肿瘤细胞减灭术及术后腹腔热灌注化疗在晚期卵巢癌治疗中的应用价值分析

目的 研究新辅助化疗(NACT)联合肿瘤细胞减灭术(CDS)及术后腹腔热灌注化疗(IPHC)治疗晚期卵巢癌的临床疗效.方法 选择86例Ⅲ～Ⅳ期卵巢癌患者,依据随机数字表法将患者分为试验组(n=43)和对照组(n=43).试验组患者行NACT联合CDS及术后IPHC治疗,对照组患者行CDS联合卡铂/顺铂化疗治疗.观察两组患者的术中和术后指标、治疗前后外周血T淋巴细胞因子水平、术后不适和不良反应发生率及临床疗效.结果 试验组患者术中腹腔积液量和失血量明显少于对照组,手术时间、术后化疗疗程和住院时间明显短于对照组(P﹤0.01).试验组患者术后发热率、感染率低于对照组,术后切口Ⅱ期愈合率高于对照组(P﹤0.05).治疗后,试验组患者的CD3+CD56+、CD3+CD4+水平及CD3+CD4+/CD3+CD8+明显高于对照组,差异有统计学意义(P﹤0.01).两组患者恶心呕吐、腹泻腹痛、便秘、肝肾毒性、骨髓抑制不良反应发生率比较,差异均无统计学意义(P﹥0.05).试验组患者的客观有效率为62.79％(27/43),高于对照组的37.21％(16/43),差异有统计学意义(P﹤0.05).结论 NACT联合CDS及术后IPHC可有效清除卵巢癌细胞,改善晚期卵巢癌患者的手术指标,提高机体的免疫能力,且不良反应发生率低,疗效较好,值得临床推广.