Treatment Of Peritoneal Surface Malignancies Research Articles

Current practices of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in the treatment of peritoneal surface malignancies: an international survey of oncologic surgeons

BackgroundThe goal of the study was to investigate the current clinical practices among oncologic surgeons regarding cytoreductive surgery (CRS) with intraoperative hyperthermic intraperitoneal chemotherapy (HIPEC).MethodsFrom September to October 2016, an online questionnaire surveyed the oncologic surgeons by email. The questionnaire included 20 multiple-choice questions of the following: eligibility for the CRS with HIPEC procedure, perioperative staging and surgery skill, assessment of residual tumors, and method used for intraperitoneal HIPEC.ResultsThe response rate was 16% (34/217). The majority of respondents (68%) worked at a university hospital. All respondents indicated that mesenteric invasion is the most crucial factor affecting treatment decision. Most surgeons (79%) used the Sugarbaker’s staging system to intraoperatively measure the extent of peritoneal invasion. The methods used to measure the extent of miliary pattern of residual tumor spread, and the amount of residual tumor after electrocauterization varied among the surgeons. Most responders (65%) used the closed system of HIPEC.ConclusionsDespite the fact that CRS HIPEC is the standard treatment for PSM, the clinical practices are very different according to each clinical situation. Nevertheless, mesenteric invasion was found to be the most important factor impacting the treatment decision-making by the majority of responders.

Transient Exocrine Pancreatic Insufficiency: First Report of an Unrecognized Complication of Cytoreductive Surgery and HIPEC.

As cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are being increasingly adopted as the standard treatment for peritoneal surface malignancies, familiarity with this procedure's adverse events is also growing. Herein, we describe an unreported adverse event of exocrine pancreatic insufficiency (EPI) following CRS and HIPEC. Patients who underwent CRS and HIPEC between 9/2016 and 9/2017 were prospectively recruited. Fecal elastase-1 (FE1) and Clostridium difficile toxins were tested in all patients in the immediate postoperative period. Patients with diarrhea who had low FE1 were started on oral pancreatic enzyme replacement therapy (PERT) and their symptomatic progression was followed. A total of 26 patients were included. Eleven patients (42.31%) developed postoperative refractory diarrhea, nine of whom had a low FE1 level. These patients were treated with PERT either directly or after completion of antibiotics course if C. difficile toxin was positive. Eight patients demonstrated symptomatic resolution of their diarrhea, and thus the diagnosis of EPI was established (30.77%). Patients with diarrhea had lower FE1 levels, and were more likely to have had a terminal ileum resection and had a longer hospital stay. Regression analysis identified the rapid rise of a patient's core temperature by >1°C within 15 minutes as the sole predictor of EPI occurrence. EPI is a potential adverse event following CRS and HIPEC and might be largely responsible for refractory diarrhea. In our patients with refractory diarrhea and low FE1, PERT provided immediate symptomatic relief. The biological basis of this phenomenon remains unclear and warrants further investigation.

Clinical studies in CRS and HIPEC: Trials, tribulations, and future directions—A systematic review

The field of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) has suffered from a lack of clinical trials to validate its expanding use. To evaluate published and ongoing clinical trials seeking to better define role of CRS/HIPEC in the treatment of peritoneal surface malignancies. Systematic review by PubMed search was performed using terms "Clinical trial," "intraperitoneal chemotherapy," and "HIPEC." ClinicalTrials.gov and EudraCT registries were searched for active clinical trials. Eligibility included CRS/HIPEC trials investigating adult patient populations from published clinical reports and/or trials currently accruing or at completion. Thirteen published trials and 57 active clinical trials were included for review. Published and ongoing U.S. and international clinical trials for CRS and HIPEC are defining important parameters that include improving patient selection, strategic sequences of treatment, cytoreductive strategies, chemotherapeutics, optimal hyperthermic temperature and timing, and toxicity profiles. Main barriers or limitations to trial development remain patient enrollment, trial design, and oncologic community collaboration. Overall progress is positive with increasing number of clinical trials throughout the world. Collaboration between surgeons and the wider oncologic community will be crucial to validate this important treatment strategy.

Treatment-related post-operative mortality after cytoreductive surgery and perioperative intraperitoneal chemotherapy

Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) has an established role in selected patients for the treatment of peritoneal surface malignancy. However, CRS/HIPEC is associated with increased risk of morbidity and mortality. The aim of this review was to identify risk factors for post-operative mortality in an attempt to improve patient outcomes post CRS/HIPEC. This is a retrospective study of prospectively collected data on 1019 patients who underwent CRS/HIPEC by the same surgical team at St George Hospital, Kogarah, Australia, between January 1996 and July 2016. During the 20-year time-period seventeen patients (1.67%) died postoperatively. A higher peritoneal cancer index (PCI), completeness of cytoreduction (CC) score, longer operative time and a volume of intra-operative transfusion were evident in the hospital mortality group and were significantly associated with postoperative mortality on univariate analysis. Postoperative complications including infection, bleeding, pneumonia, fistula, collection and pancreatic leak were also associated with post-operative mortality. The most common cause of death was sepsis (n=15, 88.2%). It is difficult to determine pre-operative factors that can be utilized as predictors of post-operative mortality, as the overall incidence of in-hospital mortality post CRS/HIPEC was very low on our unit. Nevertheless, a cascade of events and learning curve was displayed.

Registries on peritoneal surface malignancies throughout the world, their use and their options

Aim: The treatment of peritoneal surface malignancies ranges from palliative care to full cytoreductive surgery (CRS) and heated intraperitoneal chemotherapy, HIPEC. Ongoing monitoring of patient recruitment and volume is usually carried out through dedicated registries. With multiple registries available worldwide, we sought to investigate the nature, extent and value of existing worldwide CRS and HIPEC registries.Methods: A questionnaire was sent out to all known major treatment centres. The questionnaire covers: general purpose of the registry; inclusion criteria in the registry; the date the registry was first established; volume of patients in the registry and description of the data fields in the registries. Finally, the population size of the catchment area of the registry was collected.Results: Twenty-seven questionnaires where returned. National databases are established in northwest European countries. There are five international general databases. Most database collect data on patients who have undergone an attempt to CRS and HIPEC. Two registries collect data on all patients with peritoneal carcinomatosis regardless the treatment. Most registries are primarily used for tracking outcomes and complications. When correlating the number of cases of CRS and HIPEC that are performed to the catchment area of the various registry, a large variation in the number of performed procedures related to the overall population was noted, ranging from 1.3 to 57 patients/million year with an average of 15 patients/1 million year.Conclusions: CRS and HIPEC is a well-established treatment for peritoneal surface malignancies worldwide. However, the coverage as well as the registration of treatment procedures differs widely. The most striking difference is the proportion of HIPEC procedures per capita which ranges from 1.3 to 57 patients per million. This suggests either a difference in patient selection, lack of access to HIPEC centres or lack of appropriate data collection.

117. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) for the treatment of peritoneal surface malignancies in the elderly

117. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) for the treatment of peritoneal surface malignancies in the elderly

Cytoreductive surgery with intraperitoneal chemotherapy in the management of peritoneal surface malignancy: a pharmacist's perspective

ObjectivesTo explore the use of intraperitoneal chemotherapy in conjunction with cytoreductive surgery for the treatment of peritoneal surface malignancy and highlight the challenges this provides for the hospital pharmacist.MethodsA literature...

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.

P6.03 - In vivo assessment of growth-inhibitory and mucin-depleting effects of bromelain and N-acetylcysteine in peritoneal carcinomatosis models

Towards the development of novel supplementary strategies for locoregional treatment of peritoneal surface malignancies, we investigated in the present study growth-inhibitory and mucin-depleting properties of bromelain (BR) and N-acetylcysteine (NAC) as single agent or combination therapy in nude m

431. Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in the treatment of peritoneal surface malignancies: Analysis of the causes of disqualification

431. Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in the treatment of peritoneal surface malignancies: Analysis of the causes of disqualification

Safety and quality outcomes in peritoneal surface malignancy patients: developing a national center for excellence in Colombia.

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS+HIPEC) is being used more frequently for the treatment of peritoneal surface malignancies. There are a paucity of data regarding safety and quality outcomes in this group of patients. The aim of this study was to evaluate safety events and quality measures in a group of patients who underwent CRS+HIPEC. All patients who underwent CRS+HIPEC procedures between December 2007 and March 2014 were included. All safety-related events and quality outcomes were reviewed. Major events were defined as occurrences in which there was harm to patient or healthcare personnel. Minor events were defined as quality or safety events in which there was potential for damage. A total of 72 patients were included. The mean Peritoneal Cancer Index for the study group was 20.5. One hundred percent compliance for informed consent, patient identification and surgical site marking, and antibiotic and venous thromboembolism prophylaxis guidelines was identified. The incidence of major safety events was 37.5%. Minor events occurred in 47.2% of patients. There was a 2.78% 30-day mortality in the study group. One in three patients undergoing CRS+HIPEC procedures experienced a major safety or quality event before, during, or after surgery. Adequate surgical care alone is not sufficient to prevent these occurrences. Active surveillance of safety events and quality leads to early detection and development of improvement plans. New CRS+HIPEC centers need to adhere to strict safety and quality guidelines to ensure excellent patient outcomes.

Peritoneal Surface Disease Severity Score as a predictor of resectability in the treatment of peritoneal surface malignancies

BackgroundWe evaluated the clinical utility of the Peritoneal Surface Disease Severity Score (PSDSS) as a preoperative predictor of resectability in the treatment of peritoneal surface malignancies. MethodsForty-nine patients were selected for cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) and were stratified according to the PSDSS retrospectively. ResultsOf 52 cytoreductive surgeries performed in 49 patients, HIPEC was performed in 33 cases (63%). We analyzed 31 cases of appendiceal and colorectal cancer patients who underwent CRS and HIPEC and 12 who underwent CRS only. 68% of the patients in whom CRS and HIPEC was performed were classified as PSDSS stage I or II. Contrastingly, all patients in whom CRS and HIPEC was unachievable were scored as PSDSS stage III or IV. ConclusionsThe outcomes of this study suggest that the PSDSS can be used as a preoperative assessment tool to predict disease resectability in the treatment of peritoneal surface malignancies.

Postoperative outcomes of laparoscopic vs open cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy for treatment of peritoneal surface malignancies

BackgroundCytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are considered the only curative treatment for many peritoneal surface malignancies. The purpose of this study was to evaluate feasibility and safety of CRS combined with HIPEC by laparoscopy for patients with limited peritoneal disease and to compare postoperative outcomes with those for an open procedure. MethodsBetween January 2011 and November 2012, all patients with low-grade pseudomyxoma peritonei (PMP) or multicystic mesothelioma (MM) and limited peritoneal disease (Peritoneal Cancer Index [PCI] less than 10) underwent CRS and HIPEC by a laparoscopic approach. The study cohort was matched with a historical cohort of patients with the same characteristics (completeness of cytoreduction, HIPEC agent, PCI ± 11 and age ± 20 years) treated with CRS and HIPEC by laparotomy. ResultsEight patients (five low-grade PMP and three MM) treated by a laparoscopic approach were compared to eight patients treated by laparotomy. All patients underwent complete cytoreductive surgery with HIPEC, and no conversion to laparotomy was needed. The median surgical length was 210 min (150–300) vs 240 (210–360), with a median hospital stay of 12 days (9–18) vs 19 (13–33). One patient had a postoperative complication (intraperitoneal haematoma treated by radiological drainage) vs four in the laparotomy group. ConclusionLaparoscopic CRS combined with HIPEC is feasible and safe for curative treatment of strictly selected patients with peritoneal surface malignancy and might reduce postoperative complications and length of hospital stay.

Morbidity and Mortality of Cytoreduction with Intraperitoneal Chemotherapy: Outcomes from the ACS NSQIP Database

Cytoreduction with intraperitoneal chemotherapy (IPC) for treatment of peritoneal surface malignancies is increasingly utilized. However, the described morbidity and mortality rates are based predominantly on the experience at high-volume centers. We analyzed the American College of Surgeons National Surgical Quality Improvement Program (NSQIP) database for a nationwide perspective on morbidity and mortality associated with IPC. The NSQIP database was queried for all patients undergoing IPC and cytoreduction from 2005 to 2011. Univariate and forward stepwise multivariate regression identified factors associated with 30-day death and morbidity. A total of 795 patients underwent IPC. Patients underwent a median of seven operative procedures (range 2-13). Median hospital stay was 9 days (range 2-79 days). A total of 521 complications occurred in 249 (31 %) patients, and there were 19 (2.3 %) mortalities. The most common complications were bleeding (15.1 %) and sepsis (14.6 %). Univariate analysis identified age ≥60 years, ascites, weight loss, recent prior operation, albumin <3 g/dl, bilirubin ≥2 mg/dl, hematocrit ≤30 %, colon, spleen, small bowel, liver, kidney, diaphragm, and gastric resections, wound classification, operative time, and intraoperative transfusion requirement as significantly associated with death and morbidity. By multivariate analysis, age ≥60 years, preoperative albumin <3 g/dl, gastrectomy, operative time, and intraoperative transfusion requirement remained significantly associated with death and morbidity. Particularly high death and morbidity rates were associated with preoperative albumin <3 g/dl (58 %), gastrectomy (62 %), and operative time of >500 min (46 %). In this nationwide cohort, the death and morbidity rate associated with cytoreduction and IPC is consistent with other large series. Age ≥60 years, albumin <3 g/dl, gastrectomy, operative time, and intraoperative transfusion requirement were associated with 30-day death and morbidity. These factors may help guide patient selection, counseling, and preoperative optimization before IPC.

Regional treatment with liquid barrier agents: A novel therapeutic option for intraperitoneal endometriosis?

Endometriosis is a frequent gynecological disease, which is characterized by the presence of endometriotic lesions, i.e. ectopic endometrial glands and stroma, outside the uterine cavity. Most of these lesions are located in the peritoneal cavity, where they induce a chronic inflammatory and angiogenic tissue response. This is often associated with the formation of peritoneal adhesions. Accordingly, endometriosis is crucially dependent on the close interaction of the ectopic endometrial tissue with the peritoneum and the peritoneal fluid. Therefore, we hypothesize in the present paper that regional treatment of endometriosis, selectively targeting the peritoneal microenvironment without inducing severe systemic side effects, may represent a promising novel treatment strategy. This may be achieved by the application of liquid barrier agents, which are already well established in clinical practice for peritoneal dialysis, treatment of peritoneal surface malignancies and prevention of postoperative adhesions. Of interest, some of these agents have been shown to exhibit anti-inflammatory, anti-oxidant and anti-tumoral properties. Thus, they may act as pleiotropic compounds, affecting multiple mechanisms, which are involved in the pathogenesis of endometriosis.

Complications and Toxicities After Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy

The purpose of our study was to evaluate the perioperative complications, toxicity, mortality rates after cytoreductive surgery (CRS), and effects of hyperthermic intraperitoneal chemotherapy (HIPEC) used in the treatment of peritoneal surface malignancies. Between September 2007 and March 2012, we performed 118 CRS and HIPEC with the closed abdominal technique on 115 patients with peritoneal carcinomatosis (PC). Systemic toxicities were graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 criteria and were analyzed from a prospectively collected database. The mean age of patients was 53.4 (range, 20-82) years; 76.3% were female. PC was synchronous to primary cancer in 53.4% of patients, metachronous in 41.5%, and recurrent in 5.1% of the patients. PCI was ≥15 in 53.4% of the patients, and CC-0 cytoreduction was achieved in 68.5% of the patients. Perioperative mortality was observed in 9 (7.6%) patients. A total of 98 complications were observed in 46 (39.0%) patients, and 4 patients underwent 6 reoperations for perioperative surgical complications. We observed toxicity in 25.4% of the patients, nephrotoxicity in 18.6%, and hematological toxicity in 13.6% of patients. No significant difference was observed among age, gender, PCI and CC scores, origin of the primary tumor, and occurrence of toxicity and surgical complications. Prolonged operation times resulted in higher complication and/or toxicity rates (P<0.01). Cytoreductive surgery and HIPEC is a combined treatment strategy for peritoneal surface malignancies with acceptable complication and toxicity rates.

Principles and Innovations in Peritoneal Surface Malignancy Treatment.

Cytoreductive surgery with heated intraperitoneal chemotherapy (CRS/HIPEC) remains a controversial treatment for malignant disease of the peritoneal cavity. We review the scientific principles underscoring the rationale for CRS/HIPEC, recent innovations and ongoing controversies. Lack of level 1 data limits the understanding of the true benefit of CRS/HIPEC.

Outcomes of Repeat Cytoreductive Surgery with Hyperthermic Intraperitoneal Chemotherapy for the Treatment of Peritoneal Surface Malignancy

Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) has improved the survival of patients with peritoneal surface malignancy. On recurrence, a repeat CRS/HIPEC is a treatment option. A retrospective analysis of 868 CRS/HIPEC procedures was performed. Type of primary, functional status, completion of resection, hospitalization, morbidity, mortality, and survival were reviewed. Sixty-two patients (7.7%) underwent a second CRS/HIPEC, including 33 patients with appendiceal primaries, 8 ovarian, 7 mesotheliomas, 4 colon cancers, and 10 various malignancies. Median follow-up was 60.8 months. Median overall survival in months was 85.3 for appendiceal cancer, 52.9 for mesothelioma, 60.1 for ovarian, and 137.4 for colon cancer. R1 resection was achieved in 43.5% after both procedures. Median survival after the second cytoreduction was 52.1 months for appendiceal cancer, 21.8 for mesothelioma, 53.9 for ovarian, and 55.7 for colon cancer. Median survival was 55.7 months for R1 resection, 20.3 months for R2a resection, and 15.5 months for R2b-R2c. Median ICU and hospital stay was 1 and 7.5 days, respectively. The 30-day morbidity after the second CRS/HIPEC was 48.4% and mortality was 3.2%. In multivariate analysis, the R status of the second CRS/HIPEC (p = 0.013) and the interval between the 2 procedures (p = 0.009) were significant in predicting improved survival. In experienced tertiary centers and for selected patients, a repeat CRS/HIPEC procedure has morbidity and mortality similar to the initial cytoreduction. Survival depends primarily on the completion of the repeat cytoreduction and favorable biology of the tumor.

The morbidity of cytoreduction/hyperthermic intraperitoneal chemoperfusion (HIPEC) in the modern era.

e14172 Background: Critics of cytoreduction/HIPEC for treatment of peritoneal surface malignancies cite high morbidity/mortality in historical published literature. With improved patient selection algorithms based upon recent clinical experience, perioperative morbidity/mortality should be comparable to the treatment of other GI malignancies. Methods: Retrospective data collection on all patients undergoing cytoreduction/HIPEC at a single institution (2 surgeons) from 2003-2011. Patient demographics, perioperative complications, mortality, and survival were analyzed (logistic regression modeling, Kaplan Meier, and Log rank testing). Results: 113 patients (45M/68F; median age 53 years) underwent 124 cytoreduction/HIPEC procedures. Primary tumor histology was colorectal adenocarcinoma (34%), appendiceal DPAM (24%), appendical adenocarcinoma (21%), mesothelioma (10%), and other (11%). 46% of patients received systemic chemotherapy prior to cytoreduction/HIPEC. Median HIPEC time was 12 hours (range 6 to 20 hours). All patients received mitomycin C at first HIPEC with 26% receiving a dose reduction. Median number of GI anastomoses was 1 (range 0-3). Median ICU stay was 1 day (range 0-21) and median length of stay (LOS) was 12 days (range 6-122). Major postoperative complications included wound infection (15%), anastomotic leak (11%), neutropenia (7%), pulmonary (5%), and thromboembolic events (2%). The reoperation rate for complications was 15%. Operative mortality at 30 and 60 days was 0% and 3%, respectively. As a surrogate for complications, LOS &gt;14 days occurred in 24% of patients. Median follow-up was 25 months (1-80 months). Median progression-free and overall survival were 26.3 and 68.5 months, respectively. An anastomotic leak was associated with increased LOS, decreased progression-free survival (15.3 months, p&lt; 0.05) and overall survival (15.3 months, p&lt; 0.005). Conclusions: Despite being stage IV disease, perioperative morbidity/mortality for cytoreduction/HIPEC is comparable to surgical treatment of primary upper GI malignancies. Patient selection and meticulous technique may be critical to avoid anastomotic leaks associated with decreased survival.

Surgery for colorectal peritoneal carcinomatosis

Peritoneal carcinomatosis occurs in patients with advanced gastrointestinal and gynecological malignancies and also in patients who experience recurrence after treatment failure of the primary tumor. Malignant disease in the peritoneal cavity is a morbid and significant predictor of a diminished survival in a cancer patient. Systemic chemotherapy alone will not be adequate to palliate or treat patients with peritoneal carcinomatosis. Cytoreductive surgery is a new surgical technique that is performed using peritonectomy procedures to allow total eradication of peritoneal tumors. Intraperitoneal chemotherapy regimens such as intraoperative hyperthermic intraperitoneal chemotherapy (HIPEC) and early postoperative intraperitoneal chemotherapy (EPIC) are effective adjuvant treatment to treat the minimal residual disease after cytoreductive surgery to reduce the risk of locoregional recurrence. A substantial body of evidence available in the current literature has documented the survival benefits of combining cytoreductive surgery and intraperitoneal chemotherapy to treat a previously fatal phase of malignancy. This review provides a summary of the developments in the understanding and treatment of peritoneal surface malignancy from colorectal cancer.