Impact of Major Complications on Patients' Quality of Life After Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy.
Hamilton Trevor D,Taylor Emily L,Cannell Amanda J,McCart J Andrea,Govindarajan Anand
Annals of surgical oncology
INTRODUCTION:Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is an effective treatment for selected patients with peritoneal surface malignancies (PSM). Although it can have significant morbidity, perioperative mortality is low. Little is known about whether major complications after CRS/HIPEC have a lasting impact on patients' quality of life (QOL). METHODS:We retrospectively reviewed data from a prospectively collected database on patients treated with CRS/HIPEC for PSM (2011-2014). Patients with CRS/HIPEC and 6-month QOL evaluation were included. Major perioperative complications (Clavien-Dindo grade 3/4) were the primary independent variable. QOL was evaluated using the validated EORTC QLQ-C30 score. The primary outcome was 6-month global health score. Secondary outcomes were individual functional and symptom domains. RESULTS:Forty-two patients were analyzed. Median age was 57.5; 64 % were female. Origin of PSM was appendix (55 %), colorectal (38 %), mesothelioma (5 %), and small bowel (2 %). Fourteen patients (33 %) had major (grade 3/4) complications. Median length of stay was 16 days; patients experiencing major complications had significantly increased length of stay (35.5 vs. 13 days, p < 0.01). Major complications included intra-abdominal abscess (9.5 %), bleeding (9.5 %), symptomatic pleural effusion (7.1 %), anastomotic leaks (7.1 %), and renal failure (2.4 %). The average global health score at 6 months was 68.1. The worst-rated symptom scores at 6 months were diarrhea (39.8) and fatigue (35.4). There were no significant differences in 6-month QOL scores between patients with and without major complications, globally or in specific domains. CONCLUSIONS:Although major complications are common after CRS/HIPEC, QOL at 6 months recovers and is similar to those without major complications.
The prognosis impact of hyperthermic intraperitoneal chemotherapy (HIPEC) plus cytoreductive surgery (CRS) in advanced ovarian cancer: the meta-analysis.
Zhang Guyu,Zhu Yimin,Liu Chongdong,Chao Guangming,Cui Ran,Zhang Zhenyu
Journal of ovarian research
BACKGROUND AND OBJECTIVE:Previous studies about the prognostic value of the HIPEC have yielded controversial results. Therefore, this study aims to assess the impact of HIPEC on patients with ovarian cancer. RESULTS:We included 13 comparative studies, and found that the overall survival (OS) and progression-free survival (PFS) in HIPEC groups were superior to groups without HIPEC treatment in the all total population (HR = 0.54,95% CI:0.45 to 0.66, HR = 0.45, 95% CI: 0.32 to 0.62). Additionally, the subgroup analysis showed that patients with advanced primary ovarian cancers also gained improved OS and PFS benefit from HIPEC (HR = 0.59,95% CI:0.46 to 0.75, HR = 0.41,95% CI:0.32 to 0.54). With regard to recurrent ovarian cancer, HIPEC was associated with improved OS (HR = 0.45,95% CI:0.24 to 0.83), but for the PFS, no correlation was observed between HIPC group and the non-HIPEC group (HR = 0.55,95% CI:0.27 to 1.11). HIPEC also led to favorable clinical outcome (HR = 0.64,95% CI:0.50 to 0.82, HR = 0.36,95% CI:0.20 to 0.65) for stage III or IV ovarian cancer with initial diagnosis. CONCLUSION:The review indicated that HIPEC-based regimens was correlated with better clinical prognosis for patients with primary ovarian cancers. For recurrent ovarian cancers, HIPEC only improved the OS but did not elicit significant value on the PFS.
What made hyperthermic intraperitoneal chemotherapy an effective curative treatment for peritoneal surface malignancy: A 25-year experience with 1,125 procedures.
Passot Guillaume,Vaudoyer Delphine,Villeneuve Laurent,Kepenekian Vahan,Beaujard Annie-Claude,Bakrin Naoual,Cotte Eddy,Gilly Francois-Noel,Glehen Olivier
Journal of surgical oncology
OBJECTIVE:To review our 25-year experience with hyperthermic intra-peritoneal chemotherapy (HIPEC). BACKGROUND:Combining cytoreductive surgery (CRS) and HIPEC as local treatments for peritoneal carcinomatosis (PC) was proposed 25 years ago. METHODS:A prospective database of all patients undergoing HIPEC for PC since 1989 was searched for clinicopathological data, 90-day morbidity and mortality, and survival. RESULTS:Among 1,125 HIPEC procedures, PC origin was colorectal (342; 30%), ovarian (271; 24%), pseudomyxoma peritonei (189; 17%), gastric (127; 11%), malignant mesothelioma (84; 8%), or other (112; 10%). Between 2004-2009 (n = 321) and 2010-2015 (n = 560), the median peritoneal cancer index decreased (11 vs. 8; P < 0.001), fewer patients underwent incomplete cytoreduction (CC2-3: 4% vs. 0.5%; P < 0.001), and more were included in randomized trials (5% vs. 16%; P < 0.001). Postoperative morbidity (52% vs. 50%, P = 0.672) was not different, but mortality significantly decreased (5% vs. 2%; P = 0.030). Median overall-survival was 42 months, and improved significantly for each 5-year period except for 2006-2010 vs. 2011-2015 (P = 0.097). The 10-year survival without recurrence was 53%, 14%, 4%, 10%, and 9% for pseudomyxoma, mesothelioma, ovarian, colorectal, and gastric PC, respectively. CONCLUSION:This study demonstrated that CRS and HIPEC provide long-term survival irrespective of PC origin, and survival improves with experience. J. Surg. Oncol. 2016;113:796-803. © 2016 Wiley Periodicals, Inc.
Efficacy of postoperative intraperitoneal hyperthermic perfusion chemotherapy with oxaliplatin + 5-Fluorouracil in the treatment of gastric cancer patients with peritoneal carcinomatosis.
Yan Kangpeng,Wu Kun,Yan Lan,Liang Lei,Yuan Yujun
Journal of B.U.ON. : official journal of the Balkan Union of Oncology
PURPOSE:To explore the effect of palliative laparoscopic resection of gastric cancer combined with intraperitoneal hyperthermic perfusion chemotherapy (IHPC) with oxaliplatin + 5-fluorouracil (5-FU) on gastric cancer patients with peritoneal carcinomatosis (PC). METHODS:90 patients definitely diagnosed with gastric adenocarcinoma and PC and admitted to our hospital from March 2013 to March 2016 were collected and divided into IHPC group (n=45) and control group (n=45). In IHPC group, IHPC with oxaliplatin + 5-FU was carried out for the first time on the first day after operation, and then it was conducted once every other day for a total of 4 times. The clinical efficacy, quality of life, adverse reactions, postoperative tumor recurrence and survival of the patients were observed and recorded. RESULTS:The total effective rates in IHPC group and control group were 62.2% (28/45) and 55.6% (25/45), respectively (p>0.05). In both groups, the curative effect was the best in moderately differentiated adenocarcinoma and worst in signet ring cell carcinoma. Besides, the effective rates of Karnofsky performance status (KPS) in the two groups after operation were 82.2% (37/45) and 75.6% (34/45), respectively (p=0.606). However, the renal function indexes, serum creatinine (sCr) and blood urea nitrogen (BUN) in the two groups of patients after operation were increased, and those in the IHPC group were higher than those in the control group (p=0.016, p=0.010). Moreover, follow-up results of patients' survival revealed that the OS and PFS in the IHPC group were significantly higher than those in the control group (p=0.041, p=0.045). CONCLUSIONS:Palliative laparoscopic resection of gastric cancer combined with IHPC with oxaliplatin +5-FU has a definite therapeutic effect on gastric cancer with PC, which can achieve a better short-term clinical therapeutic effect and better postoperative quality of life.
Docetaxel combined with intraperitoneal hyperthermic perfusion chemotherapy and hyperthermia in the treatment of advanced ovarian cancer.
Zhang Ting,Pan Qiong,Xiao Songshu,Li Lijie,Xue Min
Ovarian cancer is a clinical type of gynecological malignant tumor with poor prognosis and a high mortality rate. At present, the primary treatment method used is surgery, with chemotherapy as an ajdunctive therapy. Thus, new short-term treatments should be identified. The aim of the present study was to investigate the short-term curative effects and safety of docetaxel combined with intraperitoneal cisplatin chemotherapy and hyperthermia treatment of advanced ovarian cancer. A total of 112 cases of advanced (stage III-IV) ovarian cancer patients confirmed by clinical diagnosis between October 2014 and December 2015 were included in the study. The patients were randomly divided into the study and control groups (n=56 cases). The control group was treated with docetaxel and intraperitoneal cisplatin hyperthermic perfusion chemotherapy, while the study group was treated with docetaxel venous chemotherapy and intraperitoneal cisplatin cyclical hyperthermic perfusion chemotherapy with BR-TRG-1 body cavity hyperthermic perfusion treatment system. Clinical treatment results for short-term curative effects and adverse reactions were compared and analyzed 8 weeks after treatment. The total effective rate of the study and control groups were 87.5 and 62.5%, respectively, and the difference was statistically significant (P<0.05). The controlled rate of ascites, remission rate of tumor and descent rate of CA125 of patients in the study group were better than patients in the control group (P<0.05). The rate of adverse reactions of patients in the study group was 39.3%, and the grade of toxicity was from I to II, while the rate of adverse reactions of patients in the control group was 55.4%, and the grade of toxicity was from II to III. The difference between the two groups was statistically significant (P<0.05). In conclusion, applying the combination of docetaxel, intraperitoneal cisplatin hyperthermic perfusion chemotherapy and hyperthermia to treat advanced ovarian cancer can improve the curative effects with little toxicity; thus, it is worthy of promotion and application.
[A Meta-Analysis of Efficacy and Adverse Effects of Lobaplatin and Cisplatin in the Treatment of Malignant Pleural Effusion].
Min Shihui,Zheng Qiangqiang,Zhang Bailu,Yan Danli,Wang Rulan,Qu Zihan,Li Lu,Liu Jiewei,Zhou Qinghua
Zhongguo fei ai za zhi = Chinese journal of lung cancer
BACKGROUND:The aim of this study is to systematically evaluate the efficacy and adverse effects of Lobaplatin and Cisplatin in the treatment of malignant pleural effusion. METHODS:The databases of Medline (PubMed), Embase, Web of Science, Cochrane, Wanfang, CNKI and VIP were retrieved so as to search the studies about the randomized controlled clinical trials (RCT) that compared the Lobaplatin and Cisplatin for malignant pleural effusion. The main outcome indicators include objective response rate, complete response, partial response, nephrotoxicity, chest pain, gastrointestinal reaction, myelosuppression, fever response and hepatotoxicity. Relative risk was used as the effect size, which was expressed as 95% confidence interval. The meta-analysis was performed using Stata 14.0 statistical software. RESULTS:A total of 12 RCTs and 720 MPE patients were included. The results showed that the ORR (RR=1.27, 95%CI: 1.15-1.40, P<0.001), CR (RR=1.39, 95%CI: 1.09-1.78, P=0.007), PR (RR=1.21, 95%CI: 1.02-1.42, P=0.026) in LBP thoracic perfusion chemotherapy were significantly higher than those in DDP thoracic perfusion chemotherapy. The incidence of nephrotoxicity (RR=0.31, 95%CI: 0.13-0.71, P=0.005) and gastrointestinal reactions (RR=0.44, 95%CI: 0.31-0.62, P<0.001) in the LBP group were significantly lower than those in DDP group. CONCLUSIONS:Compared with DDP pleural perfusion chemotherapy, the ORR, CR and PR of LBP pleural perfusion chemotherapy for MPE are significantly better than DDP, and its nephrotoxicity and gastrointestinal reactions are remarkably lower than DDP.
Prognostic factors associated with cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy in recurrent ovarian cancer.
Ayhan Ali,Akilli Huseyin
International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics
OBJECTIVE:To identify factors affecting survival for women undergoing cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy (HIPEC). METHODS:A retrospective study at Baskent University School of Medicine, Ankara, Turkey. Data were evaluated for 71 women with recurrent ovarian cancer who underwent cytoreductive surgery with R0 resection plus HIPEC between 2016 and 2019. Potential factors affecting survival (platinum sensitivity, bevacizumab administration before HIPEC, albumin and CA125 levels, presence of ascites, age, number of chemotherapy lines, and time interval between last chemotherapy and HIPEC) were evaluated. Complications of HIPEC were documented. RESULTS:The median age was 58 years, and the median follow-up was 12 months. In univariate analyses, platinum sensitivity, albumin level, and time since last chemotherapy cycle affected overall survival. In multivariate Cox regression analysis, use of bevacizumab before HIPEC (hazard ratio [HR], 6.7; 95% confidence interval [CI], 1.39-32.3; P=0.018) and presence of ascites (HR, 5.3; 95% CI, 1.65-17.5; P=0.005) were independent negative prognostic factors. Seven (8.9%) women experienced grade III-IV complications. CONCLUSION:In recurrent ovarian cancer, HIPEC is a promising treatment with mild-to-moderate toxicity. However, the presence of ascites and progression under bevacizumab treatment before HIPEC seem to be negative prognostic factors; these findings will be important for patient selection.
Hyperthermic intraperitoneal chemotherapy does not improve survival in advanced ovarian cancer.
Vergote Ignace,Harter Philipp,Chiva Luis
Despite its widespread use, until recently, there was no randomized evidence for hyperthermic intraperitoneal chemotherapy (HIPEC) versus surgery without HIPEC for ovarian cancer. Recently, a Dutch study (OVHIPEC) reported benefits in both progression-free survival (PFS) and overall survival (OS) gained from the use of HIPEC at the time of interval debulking surgery (IDS) for stage III ovarian carcinoma, whereas a Korean randomized trial failed to show a benefit of HIPEC for patients with ovarian cancer undergoing primary debulking surgery or IDS. In colorectal cancer, 2 randomized trials failed to show an improvement in survival with HIPEC. In addition to these contradictory results, there are a number of aspects of the Dutch OVHIPEC trial in ovarian cancer that can be criticized. Some criticisms include a reduction of the number of patients needed to be randomized because of too slow accrual; much lower PFS and OS in both arms than expected according to the statistical plan; the small size of the study, with imbalances between the 2 arms (eg, more low-grade tumors in the HIPEC arm); the timing of randomization before the start of IDS; the lack of clear inclusion criteria for neoadjuvant chemotherapy; and the heterogeneity of the results, with the largest effect shown at the smaller centers. Furthermore, it is questionable whether the adverse events were reported completely. In conclusion, data about HIPEC for ovarian cancer in general are not convincing, and they do not change the standard of care, which remains for ovarian cancer surgery and intravenous chemotherapy.
Cellular Immunoprofile of Peritoneal Environment During a HIPEC Procedure.
Franko Jan,Brahmbhatt Rushin,Tee May,Raman Shankar,Ferrel Benjamin,Gorvet Marc,Andres Matthew
Annals of surgical oncology
BACKGROUND:We characterized the peritoneal immune cellular profile during cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) in this pilot study. METHODS:We prospectively performed flow cytometric analysis of peritoneal fluid collected at laparotomy and during HIPEC at 0, 30, 60, and 90 min. Analysis consisted of standard flow cytometric leukocyte gating and the use of antibodies for stem cells, B lymphocytes, T-helper, T-suppressor, and natural killer (NK) cells. RESULTS:The mean peritoneal carcinomatosis index (PCI) score was 19.8 ± 11.5 (median 19). Twelve patients had a completeness of cytoreduction (CCR) score of 0-1, and three patients had a CCR score of ≥ 2 (20%). The proportion of peritoneal NK cells remained stable (p = 0.655) throughout perfusion. The CD4/CD8 ratio (p = 0.019) and granulocyte/lymphocyte ratio (p = 0.018) evolved during cytoreduction, with no further change during HIPEC. Two distinct temporal patterns of peritoneal T lymphocytes became evident (the 'high' and 'low' CD4/CD8 ratio groups) and patients maintained their high versus low peritoneal CD4/CD8 ratio status throughout the duration of HIPEC. High CD4/CD8 was associated with longer cytoreduction (p = 0.019) and borderline higher PCI score (p = 0.058). No association was identified with age (p = 0.131), sex (p = 1.000), CCR status (p = 0.580), occurrence of complication (p = 0.282), or ascites volume (p = 0.713). CONCLUSION:The cellular immunoprofile of peritoneal fluid during HIPEC is stable but changes during cytoreduction. Two distinct immune groups emerged, based on CD4/CD8 ratios in the peritoneal perfusate. Further studies are warranted to evaluate peritoneal immunity and the clinical significance of novel peritoneal immune phenotype.
Systemic inflammatory response after hyperthermic intraperitoneal chemotherapy (HIPEC): The perfusion protocol matters!
Roth Lilian,Eshmuminov Dilmurodjon,Laminger Felix,Koppitsch Claudia,Schneider Marcel,Graf Theresia Reding,Gupta Anurag,Kober Fritz,Roka Sebastian,Gertsch Philippe,Lehmann Kuno
European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology
BACKGROUND:CRS/HIPEC gained acceptance as a treatment for selected patients with peritoneal metastasis. However, the pathophysiology behind HIPEC is poorly understood, and a variety of regimens are currently in use. In this study, we describe for the first-time changes in the postoperative systemic inflammatory reaction, highly different among HIPEC treatment protocols. METHODS:HIPEC was performed with three protocols, different with regard to perfusion times and drugs: (mitomycinC/doxorubicin, 90min), (cisplatin, 90min) (oxaliplatin, 30min). Serial blood samples were assessed for C-reactive protein (CRP), white blood cells (WBC), pancreatic stone protein (PSP) and bacterial component (16s rDNA). The study was approved by the local ethics committee and registered at clinicaltirals.gov (NCT02741167). RESULTS:Overall, 140 patients from two European centers were included. In patients without postoperative complications, a secondary peak of inflammatory parameters, CRP (p = 0.015) and PSP (p = 0.004) was observed after HIPEC for 90 min with mitomycinC/doxorubicin or cisplatin but not after 30 min oxaliplatin. In patients after 90 min HIPEC, postoperative serum bacterial 16srDNA level were 2.1 times higher (95% CI 0.646-3.032, p = 0.015) compared to 30 min oxaliplatin. DISCUSSION:In conclusion, we identified a secondary inflammatory reaction after 90 min HIPEC, either with mitomycinC/doxorubicin or cisplatin, not observed after short course HIPEC with oxaliplatin. This protocol dependent physiology of acute phase proteins should be known in the clinical management of patients after HIPEC.
Comparison of open and closed hyperthermic intraperitoneal chemotherapy: Results from the United States hyperthermic intraperitoneal chemotherapy collaborative.
Leiting Jennifer L,Cloyd Jordan M,Ahmed Ahmed,Fournier Keith,Lee Andrew J,Dessureault Sophie,Felder Seth,Veerapong Jula,Baumgartner Joel M,Clarke Callisia,Mogal Harveshp,Staley Charles A,Zaidi Mohammad Y,Patel Sameer H,Ahmad Syed A,Hendrix Ryan J,Lambert Laura,Abbott Daniel E,Pokrzywa Courtney,Raoof Mustafa,LaRocca Christopher J,Johnston Fabian M,Greer Jonathan,Grotz Travis E
World journal of gastrointestinal oncology
BACKGROUND:Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) for peritoneal carcinomatosis can be performed in two ways: Open or closed abdominal technique. AIM:To evaluate the impact of HIPEC method on post-operative and long-term survival outcomes. METHODS:Patients undergoing CRS with HIPEC from 2000-2017 were identified in the United States HIPEC collaborative database. Post-operative, recurrence, and overall survival outcomes were compared between those who received open closed HIPEC. RESULTS:Of the 1812 patients undergoing curative-intent CRS and HIPEC, 372 (21%) patients underwent open HIPEC and 1440 (79%) underwent closed HIPEC. There was no difference in re-operation or severe complications between the two groups. Closed HIPEC had higher rates of 90-d readmission while open HIPEC had a higher rate of 90-d mortalities. On multi-variable analysis, closed HIPEC technique was not a significant predictor for overall survival (hazards ratio: 0.75, 95% confidence interval: 0.51-1.10, = 0.14) or recurrence-free survival (hazards ratio: 1.39, 95% confidence interval: 1.00-1.93, = 0.05) in the entire cohort. These findings remained consistent in the appendiceal and the colorectal subgroups. CONCLUSION:In this multi-institutional analysis, the HIPEC method was not independently associated with relevant post-operative or long-term outcomes. HIPEC technique may be left to the discretion of the operating surgeon.
[Hyperthermic intraperitoneal chemotherapy].
Leebmann H,Piso P
Der Chirurg; Zeitschrift fur alle Gebiete der operativen Medizen
Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are recognized as the standard of care for selected patients with peritoneal malignancies. A complete macroscopic cytoreduction is the basis for a successful multimodal treatment. The significance of intraperitoneal chemotherapy is still under discussion. This review explains the principles and the value of HIPEC within the multimodal treatment context.
The Onset of Intra-Abdominal Adhesions During Closed-Abdomen Hyperthermic Intraperitoneal Chemotherapy.
Lotti Marco,Giulii Capponi Michela,Campanati Luca,Poiasina Elia,Ansaloni Luca,Poletti Eugenio,Frigerio Luigi
Journal of laparoendoscopic & advanced surgical techniques. Part A
INTRODUCTION:Hyperthermic intraperitoneal chemotherapy (HIPEC) is delivered after cytoreductive surgery (CRS) in selected patients with peritoneal carcinomatosis. The closed-abdomen technique, preferred by many centers, prevents heat loss and drug spillage, but does not warrant homogeneous distribution of the perfusion fluid (PF). The hypothesized formation of intra-abdominal adhesions during the closed-abdomen perfusion period has never been described. MATERIALS AND METHODS:From March 2014 to April 2016, 10 consecutive patients with peritoneal carcinomatosis, selected for CRS, underwent the Laparoscopy-Enhanced HIPEC technique to explore the abdominal cavity during the perfusion. The aim of the study was to investigate the incidence and the extent of intra-abdominal adhesions that are formed after CRS during the perfusion period of closed-abdomen HIPEC. RESULTS:During the perfusion, adhesions developed in 70% of the patients. Adhesions developed mainly in the period between the closure of the abdomen and the subsequent filling of the abdomen with the PF. After their first division, during the following perfusion period, adhesions between the bowel and the abdominal wall reformed in 3 patients (30%). CONCLUSIONS:Intra-abdominal adhesions are frequently formed during closed-abdomen HIPEC and can hamper the adequate circulation of the PF. The Laparoscopy-Enhanced technique enables the early detection and the division of any intra-abdominal adhesions.
Nephrotoxicity and long-term survival investigations for patients with peritoneal carcinomatosis using hyperthermic intraperitoneal chemotherapy with cisplatin: A retrospective cohort study.
Ye Jinning,Ren Yufeng,Wei Zhewei,Peng Jianjun,Chen Chuangqi,Song Wu,Tan Min,He Yulong,Yuan Yujie
BACKGROUND & PURPOSE:Cytoreductive surgery (CRS) plus Hyperthermic intraperitoneal chemotherapy (HIPEC) is an effective measure for peritoneal carcinomatosis. The cisplatin (CP) applied in HIPEC carries a risk of kidney injury. This study aims to investigate CP-induced nephrotoxicity post HIPEC and to explore its risk factors. METHODS:From January 2012 to July 2013, 99 patients undergoing CRS + HIPEC were retrospectively reviewed. Patients were divided into CP and Non-CP HIPEC groups. The RIFLE classification was used to assess the severity of acute kidney injury (AKI). Renal and hepatic function, concentrations of tumor markers, and postoperative outcomes were compared between groups. RESULTS:47 (47.5%) patients were in the CP HIPEC group, with 52 (52.5%) patients in the Non-CP HIPEC group. 11 (11.1%) patients developed AKI, with 10 of them from the CP HIPEC group. Two patients with CP-contained HIPEC developed acute renal failure. Plasma levels of both urea nitrogen and creatinine were significantly increased in the CP HIPEC group compared with the Non-CP HIPEC group (P < 0.01). However, postoperative pain (scaled score, 4.2 vs. 3.8; P = 0.279), length of hospital stay (18.1 vs. 20.2 days; P = 0.285), hospital costs ($1 3182 vs. $12 640; P = 0.465) and incidence of postoperative complication (25.5% vs. 17.3%; P = 0.337) were similar in both groups, with comparable 3-year overall survival observed (38.6% vs. 31.8%, P = 0.319). A multivariate analysis indicated that use of CP was an independent risk factor for AKI (P = 0.017, 95% CI: 1.277-4.155). CONCLUSIONS:Application of CP during HIPEC is associated with an increased risk of nephrotoxicity, without promising long-term survival benefit.
Peritoneal Cancers and Hyperthermic Intraperitoneal Chemotherapy.
Pletcher Eric,Gleeson Elizabeth,Labow Daniel
The Surgical clinics of North America
Cytoreductive surgery followed by hyperthermic intraperitoneal chemotherapy is an aggressive, potentially curative approach used to treat locoregional disease associated with primary and secondary malignancies of the peritoneum. It involves resection of all macroscopic disease larger than 2.5 mm, followed by instillation of hyperthermic chemotherapy directly into the peritoneum for higher drug exposure to microscopic disease. In select patients with primary peritoneal mesothelioma, pseudomyxoma peritonei, colorectal adenocarcinoma, appendiceal adenocarcinoma, or ovarian cancer, with no extra-abdominal metastasis and limited involvement of the peritoneum, the procedure can be performed to increase overall survival.
Operating personnel safety during the administration of Hyperthermic Intraperitoneal Chemotherapy (HIPEC).
Kyriazanos Ioannis,Kalles Vasileios,Stefanopoulos Anastasios,Spiliotis John,Mohamed Faheez
Cytoreductive surgery (CRS) and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) is increasingly used in the treatment of peritoneal malignancies. The administration of HIPEC after complete cytoreduction offers the combination of the pharmacokinetic advantages inherent to the intraperitoneal delivery of cytotoxic chemotherapy, with the direct cytotoxic effects of hyperthermia, and has been reported to offer significantly improved patient outcomes. As a result, this novel method disseminates rapidly, with many surgical teams having developed peritoneal malignancy treatment programs. Protocols are needed for the introduction, handling, and management of chemotherapeutic agents in the operating room to minimize risk to the staff involved in the procedure. The personnel exposure during CRS and HIPEC may arise from different routes, such as air contamination, direct contact, manipulation of perfusates or chemotherapy solutions, and manipulation of objects/tissues exposed to chemotherapeutics. Guidelines for safe administration of HIPEC including environmental contamination risk management, personal protective equipment, and occupational health issues are yet to be established. This review summarizes the existing evidence regarding the safety considerations of HIPEC administration.
Hematological toxicities associated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy.
Wong Evelyn Y T,Tan Grace H C,Kumar Mrinal,Teo Melissa C C
Asia-Pacific journal of clinical oncology
INTRODUCTION:Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) have been found to prolong survival in selected patients with peritoneal disease, but the extent of cytoreduction and chemoperfusion can result in systemic toxicities. We evaluate the incidence of perioperative hematological complications and its associated risk factors. METHODS:Retrospective analysis of a prospectively collected database of CRS-HIPEC cases between April 2001 and October 2016 was performed. Patients were stratified based on the clinicopathological characteristics, perioperative incidence, grade, and duration of leukopenia (white blood cells < 4000/mm ), neutropenia (absolute neutrophils < 2000/mm ), and thrombocytopenia (platelets < 140 000/mm ). RESULTS:Two hundred and thirty-five CRS-HIPEC were performed in 220 patients with peritoneal metastasis of colorectal, ovarian, primary peritoneal, appendiceal, or mesothelioma origins. The incidences of leukopenia, neutropenia, and thrombocytopenia were 15.3%, 3.8%, and 37.9%, respectively. Median time to onset was 1 day (0-16 days), 0 day (0-2 days), and 1 day (1-2 days), respectively, after operation. Median duration of leukopenia, neutropenia, and thrombocytopenia was 1 day (1-3 days), 1 day (1-2days), and 3 days (range 0-16 days), respectively. Age > 60 (odds ratio [OR] 0.229 [95% CI: 0.105-0.502], P < .001) and the use of prior chemotherapy (OR 2.46 [95% CI: 1.24, 4.83], P = .010) were independent risk factors for thrombocytopenia on multivariable logistic regression. CONCLUSION:Hematological toxicities are common after hyperthermic intraperitoneal chemotherapy with thrombocytopenia being most common. Patients with age > 60, and who have undergone chemotherapy, are at risk of these toxicities and should be closely monitored post CRS-HIPEC.
An overview and update of hyperthermic intraperitoneal chemotherapy in ovarian cancer.
de Bree Eelco,Michelakis Dimosthenis
Expert opinion on pharmacotherapy
INTRODUCTION:Despite, the strong rationale and evidence of the benefit of postoperative intraperitoneal chemotherapy in advanced ovarian cancer, it has not been widely adopted, mainly due to its high morbidity and logistical difficulties. Intraoperative hyperthermic intraperitoneal chemotherapy (HIPEC) is a more tolerable and technically feasible method of intraperitoneal chemotherapy, whereas other potential advantages include homogenous drug distribution, application before tumor regrowth and combination with hyperthermia, which is directly cytotoxic and enhances the efficacy of many drugs. AREAS COVERED:In this review, the authors explain the rationale and indications for cytoreductive surgery (CRS) and HIPEC in advanced ovarian cancer. Data of major clinical studies, meta-analyses, and recent randomized trials are discussed. EXPERT OPINION:After many encouraging clinical studies and meta-analyses, a recent randomized study demonstrated survival benefit for HIPEC during interval CRS in primary ovarian cancer, without increased morbidity, whereas another implied its benefit in recurrent ovarian cancer. Results of recently completed and numerous ongoing randomized studies will further determine the benefit of HIPEC in ovarian cancer at different time points. Patient selection and appraisal of the best protocols are crucial. The field of gynecological oncology will most likely evolve to include HIPEC eventually as a routine treatment for ovarian cancer.
A guide to establishing a hyperthermic intraperitoneal chemotherapy program in gynecologic oncology.
Chambers Laura M,Costales Anthony B,Crean-Tate Katie,Kuznicki Michelle,Morton Molly,Horowitz Max,Jagielo Tiffany,Rose Peter G,Michener Chad,Vargas Roberto,Debernardo Robert
Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) may be used to treat peritoneal based malignancies, such as epithelial ovarian cancer (EOC). Despite results of clinical trials supporting an increasing indication for HIPEC in EOC, concerns have existed regarding morbidity and challenges with initiating HIPEC at an institutional level. The objective of this review is to describe evidence-based recommendations to guide implementation of a HIPEC program, following our experience at a high-volume tertiary care center. Establishing a HIPEC program requires building a multi-disciplinary team, including gynecologic oncologists, anesthesia, nursing, perfusionists and pharmacists. Team members require education regarding HIPEC protocols, toxic waste and spill management, and personal protective equipment (PPE). Required equipment includes chemotherapy certified PPE and a HIPEC pump which is connected to inflow and outflow catheters placed within the peritoneal cavity. During the procedure, 3-6 L of a hyperthermic perfusate, composed of a isotonic crystalloid vehicle and the chemotherapy of choice, is infused through the peritoneal cavity with goal temperature of 41-43 °C. Prior to HIPEC infusion, surgical teams must communicate with anesthesia and pharmacy. In patients receiving HIPEC with cisplatin, furosemide and mannitol should be administered one hour prior to chemotherapy to ensure adequate diuresis. Sodium thiosulfate may also be considered for renal protection (van Driel et al., n.d. ). We utilize a multi-agent pre-medication protocol prior to HIPEC infusion to reduce hypersensitivity reactions, renal toxicity and post-operative nausea and vomiting. Limited data exists to support the optimal regimen for HIPEC at the time of CRS in women with EOC. From our experience, we favor use of cisplatin 100 mg/m alone or in combination with paclitaxel 135-175 mg/m2 with 90 min of total perfusion time. Close attention to temperature and glycemic control is essential during the procedure, as electrolyte derangements including hyperglycemia, lactic acidosis and hypokalemia may occur. Continuous patient monitoring and proactive management of abnormalities that arise during HIPEC is imperative to decrease patient morbidity and mortality.
Efficacy of neoadjuvant chemotherapy combined with intraperitoneal hyperthermic chemotherapy in advanced ovarian cancer.
Xu Zhimin,Ge Xingping,Zhang Tianmei,Shi Yanmei,Sun Meiling
Journal of B.U.ON. : official journal of the Balkan Union of Oncology
PURPOSE:To explore the efficacy and safety of neoadjuvant chemotherapy (NAC) combined with cytoreductive surgery (CRS) and postoperative intraperitoneal hyperthermic chemotherapy (IPHC) in the treatment of advanced ovarian cancer. METHODS:132 patients with advanced ovarian cancer admitted to our hospital from May 2013 to May 2016 were enrolled and randomly divided into control group (n=44), IPHC group (n=44) and NAC+IPHC group (n=44). The patients in the control group underwent CRS and postoperative TP chemotherapy (iv. drip of paclitaxel + peritoneal perfusion of cisplatin), those in IPHC group underwent the CRS and postoperative IPHC+TP chemotherapy, and those in the NAC+IPHC group received two cycles of preoperative NAC and postoperative IPHC+TP chemotherapy. The surgery indexes (operation time, amount of intraoperative bleeding, diameter of tumor and number of metastatic foci) were recorded. The clinical effective rate, changes in levels of serum tumor markers and adverse reactions were evaluated. Moreover, the tumor recurrence and survival of patients after treatment were recorded. RESULTS:In NAC + IPHC group, the operation time, amount of intraoperative bleeding and of ascites, diameter of tumor and number of metastatic foci were all significantly reduced, and the optimal cytoreduction rate was increased compared with IPHC group and control group. The clinical effective rate was 43.2% (19/44), 61.4% (27/44) and 72.7% (32/44), respectively, in the three groups, with significant differences, and the clinical effective rate was obviously higher in NAC+IPHC group than in control group, while it had no significant difference in IPHC group compared with NAC+IPHC group or control group. After treatment, the levels of serum human epididymis protein 4 (HE4) and carbohydrate antigen 125 (CA125) were evidently higher in NAC + IPHC group than in IPHC group, while they were also evidently higher in IPHC group than in control group. According to the follow-up results, the 1-year recurrence rate in NAC+IPHC group was remarkably lower than in control group, and the median progression-free survival in NAC+IPHC group and IPHC group was remarkably longer than in control group, while it had no significant difference between NAC+IPHC group and IPHC group. The median overall survival had no statistically significant differences among the three groups. CONCLUSIONS:NAC combined with IPHC can significantly reduce the perioperative risk, increase the optimal cytoreduction rate and raise the clinical effective rate of CRS in the treatment of advanced ovarian cancer. Moreover, patients have good tolerance, and both tumor progression and survival of patients are significantly improved.
Hyperthermic intraperitoneal chemotherapy (HIPEC) for ovarian cancer recurrence: systematic review and meta-analysis.
Cianci Stefano,Riemma Gaetano,Ronsini Carlo,De Franciscis Pasquale,Torella Marco,Schiattarella Antonio,La Verde Marco,Colacurci Nicola
Background:Ovarian cancer is the first cause of death among gynecological malignancies with a high incidence of recurrence. Different treatment options are suitable to prolong the survival rate of these patients. Over the last years, one of the most intriguing methods, adopted in different oncologic centers worldwide, is the hyperthermic intraperitoneal chemotherapy (HIPEC). Methods:A meta-analysis was performed to value the role of HIPEC for ovarian cancer recurrence. Search strategy was conducted with a combination of the following keywords: "ovarian recurrence, ovarian cancer recurrence, peritoneal cancer recurrence, ovarian recurrence AND HIPEC, secondary cytoreduction HIPEC". Seven studies were selected for analysis. Results:In women with recurrent ovarian cancer (ROC), the use of HIPEC in addition to cytoreductive surgery and chemotherapy significantly improved 1-year overall survival (OS) when compared to protocols without HIPEC (OR 2.42; 95% CI, 1.06-5.56; P=0.04; I=4%). The improvement in OS was maintained significant also after 2, 3 and 5 years respectively (OR 3.33; 95% CI, 1.81-6.10; P<0.01; I=0%), (OR 4.22; 95% CI, 2.07-8.60; P<0.01; I=52%), (OR 5.17; 95% CI, 1.40-19.09; P=0.01; I=82%). Conclusions:HIPEC seems to have an effective role to prolong survival in patients affected by ROC.
Treatment of PERItoneal disease in Stomach Cancer with cytOreductive surgery and hyperthermic intraPEritoneal chemotherapy: PERISCOPE I initial results.
van der Kaaij R T,Wassenaar E C E,Koemans W J,Sikorska K,Grootscholten C,Los M,Huitema A,Schellens J H M,Veenhof A A F A,Hartemink K J,Aalbers A G J,van Ramshorst B,Boerma D,Boot H,van Sandick J W
The British journal of surgery
BACKGROUND:The role of cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (HIPEC) in gastric cancer is unknown. This non-randomized dose-finding phase I-II study was designed to assess the safety and feasibility of HIPEC, following systemic chemotherapy, in patients with gastric cancer and limited peritoneal dissemination. The maximum tolerated dose of normothermic intraperitoneal docetaxel in combination with a fixed dose of intraperitoneal oxaliplatin was also explored. METHODS:Patients with resectable cT3-cT4a gastric adenocarcinoma with limited peritoneal metastases and/or tumour-positive peritoneal cytology were included. An open HIPEC technique was used with 460 mg/m hyperthermic oxaliplatin for 30 min followed by normothermic docetaxel for 90 min in escalating doses (0, 50, 75 mg/m ). RESULTS:Between 2014 and 2017, 37 patients were included. Of 25 patients who completed the full study protocol, four were treated at dose level 1 (0 mg/m docetaxel), six at dose level 2 (50 mg/m ) and four at dose level 3 (75 mg/m ). At dose level 3, two dose-limiting toxicities occurred, both associated with postoperative ileus. Thereafter, another 11 patients were treated at dose level 2, with no more dose-limiting toxicities. Based on this, the maximum tolerated dose was 50 mg/m intraperitoneal docetaxel. Serious adverse events were scored in 17 of 25 patients. The reoperation rate was 16 per cent (4 of 25) and the treatment-related mortality rate was 8 per cent (2 patients, both in dose level 3). CONCLUSION:Gastrectomy combined with cytoreductive surgery and HIPEC was feasible using 460 mg/m oxaliplatin and 50 mg/m normothermic docetaxel.
Indications for hyperthermic intraperitoneal chemotherapy with cytoreductive surgery: a systematic review.
Auer Rebecca C,Sivajohanathan Duvaraga,Biagi Jim,Conner James,Kennedy Erin,May Taymaa
European journal of cancer (Oxford, England : 1990)
The purpose of the present review was to describe evidence-based indications for hyperthermic intraperitoneal chemotherapy (HIPEC), with cytoreductive surgery (CRS), in patients with a diagnosis of mesothelioma, appendiceal (including appendiceal mucinous neoplasm), colorectal, gastric, ovarian or primary peritoneal carcinoma. Relevant studies were identified from a systematic MEDLINE and EMBASE search of studies published from 1985 to 2019. Studies were included if they were RCTs. If no RCTs were identified, prospective and retrospecctive comparative studies (where confounders are controlled for studies with greater than 30 patients) were included. Overall survival, progression-free survival, recurrence-free survival, adverse events and quality of life data were extracted. For patients with newly diagnosed, primary stage III epithelial ovarian, fallopian tube or primary peritoneal carcinoma, HIPEC with CRS should be considered for those with at least stable disease following neoadjuvant chemotherapy at the time of interval CRS if complete or optimal cytoreduction is achieved. There is insufficient evidence to recommend the addition of HIPEC when primary CRS is performed for patients with newly diagnosed, primary advanced epithelial ovarian, fallopian tube or primary peritoneal carcinoma or in those with recurrent ovarian cancer outside of a clinical trial. There is insufficient evidence to recommend HIPEC with CRS for the prevention of or for the treatment of peritoneal colorectal carcinomatosis outside of a clinical trial. There is insufficient evidence to recommend HIPEC with CRS for the prevention of or for the treatment of gastric peritoneal carcinomatosis outside of a clinical trial. There is insufficient evidence to recommend HIPEC with CRS in patients with malignant peritoneal mesothelioma or in those with disseminated mucinous neoplasm in the appendix as a standard of care; however, these patients should be referred to HIPEC specialty centres for assessment for treatment as part of an ongoing research protocol.