Use Of Hyperthermic Intraperitoneal Chemotherapy Research Articles

NIRVANA-1: maintenance therapy with niraparib versus niraparib-bevacizumab in patients with advanced ovarian cancer.

Following the results of the PRIMA and PAOLA-1 trials, the most effective maintenance strategy for International Federation of Gynecology and Obstetrics stage III patients is still debated, raising the question which of those two maintenance strategies is the most effective: PARP inhibitors alone or PARP inhibitors in combination with bevacizumab. The ongoing NIRVANA-1 study will try to answer this question by assessing the efficacy and safety of niraparib+bevacizumab in comparison with niraparib alone after adjuvant chemotherapy for completely resected stage III patients. Stratification factors include tumor BRCA status, International Federation of Gynecology and Obstetrics stage (IIIA vs IIIB/IIIC) and the use of hyperthermic intraperitoneal chemotherapy during surgery - within the OVHIPEC-2 trial. The primary end point will be progression-free survival rate at 24months. Safety, median progression-free survival and overall survival will also be studied.

Experience of cytoreduction with peritonectomy and hyperthermic intraperitoneal chemotherapy in ovarian cancer

Currently, epithelial ovarian cancer is diagnosed in advanced stages (EC IIIC) in 75-80% of cases worldwide. In this group of patients treatment with neoadjuvant chemotherapy is started, followed by interval cytoreduction of residual disease and even require peritonectomy with application of hyperthermic intraperitoneal chemotherapy (HIPEC). To identify the overall survival and progression-free survival associated with peritonectomy, in patients with peritoneal carcinomatosis secondary to ovarian cancer treated in the oncology gynecology service from January 2009 to January 2019 at the UMAE Hospital de Oncología Centro Médico Nacional Siglo XXI. Observational, descriptive, cross-sectional, retrospective study, information was obtained from the clinical file of patients treated with peritonectomy with the use of hyperthermic intraperitoneal chemotherapy in the gynecological oncology service from January 2009 to January 2019 at the UMAE Hospital de Oncología Centro Médico Nacional Siglo XXI. Information was obtained from a total of 36 patients (n=100%), 36.1% received intraperitoneal chemotherapy and 63.8% underwent cytoreduction without the application of intraoperative chemotherapy. The most frequently used drug was cisplatin followed by mitomycin. There was no statistical significance when comparing both groups, however there was a trend in favor of the use of intraoperative chemotherapy by obtaining a greater number of months in terms of overall survival. Peritonectomy with hyperthermic intraperitoneal chemotherapy is an option in selected patients with advanced stage ovarian cancer in primary and recurrent surgery, as well as in patients with platinum-resistant ovarian cancer.

HIPEC in Ovarian Cancer Is the Future… and Always Will Be? Results from a Spanish Multicentric Survey.

Ovarian cancer is the leading cause of death due to gynecological tumors in the female population. Despite optimal first-line treatment, including cytoreduction and platinum-based systemic chemotherapy, recurrences are frequent. The use of hyperthermic intraperitoneal chemotherapy (HIPEC) has been criticized, especially because of the lack of randomized controlled trials (RCTs) with convincing results to support the use of HIPEC in patients with ovarian cancer with peritoneal dissemination. In 2018, the clinical trial published by Van Driel et al. reported improved outcomes in favor of HIPEC treatment with cisplatin. In this study, we conducted a national survey within the Spanish group of peritoneal surgical oncology (Grupo Español de Cirugía Oncológica Peritoneal, GECOP) to explore the impact of the results of this RCT on clinical practice. A total of 33 groups completed the survey. Routine clinical practice was not changed in 28 of the 33 groups (85%) based on the results of the Van Driel trial. Despite the results of this RCT, most groups considered that more RCTs are needed and that, in the future, HIPEC may become the standard of care. In conclusion, the results from RCTs evaluating HIPEC treatment in patients with ovarian cancer has not been transferred to clinical practice.

Novel Multi-Modal Therapies and Their Prognostic Potential in Gastric Cancer.

Gastric cancer has a poor prognosis and involves metastasis to the peritoneum in over 40% of patients. The optimal treatment modalities have not been established for gastric cancer patients with peritoneal carcinomatosis (GC/PC). Although studies have reported favourable prognostic factors, these have yet to be incorporated into treatment guidelines. Hence, our review aims to appraise the latest diagnostic and treatment developments in managing GC/PC. A systematic review of the literature was performed using MEDLINE, EMBASE, the Cochrane Review, and Scopus databases. Articles were evaluated for the use of hyperthermic intraperitoneal chemotherapy (HIPEC) and pressurised intraperitoneal aerosolised chemotherapy (PIPAC) in GC/PC. A meta-analysis of studies reporting on overall survival (OS) in HIPEC and comparing the extent of cytoreduction as a prognostic factor was also carried out. The database search yielded a total of 2297 studies. Seventeen studies were included in the qualitative and quantitative analyses. Eight studies reported the short-term OS at 1 year as the primary outcome measure, and our analysis showed a significantly higher OS for the HIPEC/CRS cohort compared to the CRS cohort (pooled OR = 0.53; p = 0.0005). This effect persisted longer term at five years as well (pooled OR = 0.52; p < 0.0001). HIPEC and CRS also showed a longer median OS compared to CRS (pooled SMD = 0.61; p < 0.00001). Three studies reporting on PIPAC demonstrated a pooled OS of 10.3 (2.2) months. Prognostic factors for longer OS include a more complete cytoreduction (pooled OR = 5.35; p < 0.00001), which correlated with a peritoneal carcinomatosis index below 7. Novel treatment strategies, such as HIPEC and PIPAC, are promising in the management of GC/PC. Further work is necessary to define their role within the treatment algorithm and identify relevant prognostic factors that will assist patient selection.

A Review of the Use of Hyperthermic Intraperitoneal Chemotherapy for Peritoneal Malignancy in Pediatric Patients.

Hyperthermic intraperitoneal chemotherapy (HIPEC) can directly target microscopic peritoneal disease, has achieved regular consideration in the treatment of several adult cancer types, and is more recently being studied in pediatrics. This review paper provides an overview of the use of this modality in pediatrics in order to identify medication choice, discuss post-operative morbidity and mortality, and evaluate impact on overall survival. Four databases were searched including Scopus, PubMed, Embase, and CINAHL and ultimately 37 papers documenting the use of this modality comprising 264 pediatric patients were included. Malignancies treated include desmoplastic small round cell tumor, rhabdomyosarcoma, angiosarcoma, colorectal carcinoma, and mesothelioma, with several rarer tumor types. Cisplatin was the most commonly used drug for HIPEC at varying concentrations for 30-90 min in duration at temperatures of approximately 41-42 °C. Reported toxicities were generally self-limited and there was no post-operative mortality. The impact on overall survival versus systemic chemotherapy and debulking surgery is uncertain due to lack of clinical trials and very small sample size across tumor subsets and the overall pediatric population. The relationship between degree of tumor burden and extent of surgical debulking needs to be further clarified. Future directions include prospective clinical trials, establishment of patient databases to facilitate standardization of HIPEC in pediatric patients, and additional approaches to optimize HIPEC.

Effectiveness of Hyperthermic Intraperitoneal Chemotherapy Associated with Cytoreductive Surgery in the Treatment of Advanced Ovarian Cancer: Systematic Review and Meta-Analysis.

The use of hyperthermic intraperitoneal chemotherapy (HIPEC) as a treatment for epithelial ovarian cancer remains controversial. Our study aims to analyze the overall survival and disease-free survival for the use of HIPEC as a treatment for advanced epithelial ovarian cancer after neoadjuvant chemotherapy. A systematic review and meta-analysis was carried out using PubMed, Cochrane, Web of Science, and ClinicalTrials.gov. A total of six studies were used, comprising a total of 674 patients. The results of our meta-analysis of all studies analyzed together (observational and randomized controlled trials (RCT)) did not achieve significant results. Contrary to the OS (HR = 0.56, 95% IC = 0.33-0.95, p = 0.03) and DFS (HR = 0.61, 95% IC = 0.43-0.86, p < 0.01) of the RCT analyzed separately, a clear impact on survival was suggested. The subgroup analysis showed that studies making use of higher temperatures (≥42 °C) for a shorter period of time (≤60 min) achieved better results for both OS and DFS, as well as the use of cisplatin as the form of chemotherapy in HIPEC. Moreover, the use of HIPEC did not increase high-grade complications. The addition of HIPEC to cytoreductive surgery demonstrates an improvement in OS and DFS for patients with epithelial ovarian cancer in advanced stages, without an increase in the number of complications. The use of cisplatin as chemotherapy in HIPEC obtained better results.

Anastomotic Leak in Ovarian Cancer Cytoreduction Surgery: A Systematic Review and Meta-Analysis.

Anastomotic leaks (AL) following ovarian cytoreduction surgery could be detrimental, leading to significant delays in commencing adjuvant chemotherapy, prolonged hospital stays and increased morbidity. The aim of this study was to investigate risk factors associated with anastomotic leaks after ovarian cytoreduction surgery. The MEDLINE (via PubMed), Cochrane Library, EMBASE and Scopus bibliographical databases were searched. Original clinical studies investigating risk factors for AL in ovarian cytoreduction surgery were included. Eighteen studies with non-overlapping populations reporting on patients undergoing cytoreduction surgery for ovarian cancer (n = 4622, including 344 cases complicated by AL) were included in our analysis. Patients undergoing ovarian cytoreduction surgery complicated by AL had a significantly higher rate of 30-day mortality but no difference in 60-day mortality. Multiple bowel resections were associated with an increased risk of postoperative AL, while no association was observed with body mass index (BMI), American Society of Anesthesiologists (ASA) score, age, smoking, operative approach (primary versus interval cytoreductive, stapled versus hand-sewn anastomoses and formation of diverting stoma), neoadjuvant chemotherapy and use of hyperthermic intraperitoneal chemotherapy (HIPEC). Multiple bowel resections were the only clinical risk factor associated with increased risk for AL after bowel surgery in the ovarian cancer population. The increased 30-day mortality rate in patients undergoing ovarian cytoreduction complicated by AL highlights the need to minimize the number of bowel resections in this population. Further studies are required to clarify any association between neoadjuvant chemotherapy and decreased AL rates.

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in ovarian cancer

The achievement of macroscopically complete tumor resection in primary debulking surgery is the most important prognostic factor in advanced ovarian cancer. This results in amedian survival benefit of >5 years. Systematic lymphadenectomy (LNE) is not indicated in advanced ovarian cancer with inconspicuous lymph nodes as it does not prolong overall survival and therefore should no longer be carried out above stage IIB with inconspicuous lymph nodes in imaging and by palpation. Primary cytoreductive surgery is the standard in advanced ovarian cancer. Neoadjuvant therapy is currently an option only if primary cytoreduction does not appear to be possible. For the use of hyperthermic intraperitoneal chemotherapy (HIPEC) in primary debulking surgery asurvival benefit has so far not been proven and therefore HIPEC is not recommended in this setting.

Poorly cohesive cells gastric carcinoma including signet-ring cell cancer: Updated review of definition, classification and therapeutic management.

While the incidence of gastric cancer (GC) in general has decreased worldwide in recent decades, the incidence of diffuse cancer historically comprising poorly cohesive cells-GC (PCC-GC) and including signet ring cell cancer is rising. Literature concerning PCC-GC is scarce and unclear, mostly due to a large variety of historically used definitions and classifications. Compared to other histological subtypes of GC, PCC-GC is nevertheless characterized by a distinct set of epidemiological, histological and clinical features which require a specific diagnostic and therapeutic approach. The aim of this review was to provide an update on the definition, classification and therapeutic strategies of PCC-GC. We focus on the updated histological definition of PCC-GC, along with its implications on future treatment strategies and study design. Also, specific considerations in the diagnostic management are discussed. Finally, the impact of some recent developments in the therapeutic management of GC in general such as the recently validated taxane-based regimens (5-Fluorouracil, leucovorin, oxaliplatin and docetaxel), the use of hyperthermic intraperitoneal chemotherapy as well as pressurized intraperitoneal aerosol chemotherapy and targeted therapy have been reviewed in depth for their relative importance for PCC-GC in particular.

Impact of hyperthermic intraperitoneal chemotherapy on genomic heterogeneity of peritoneal metastases in stage IV gastroesophageal adenocarcinoma.

312 Background: Programmed death ligand 1 (PD-L1) expression and tumor mutational burden (TMB) are potential biomarkers for response to therapy. Heterogeneity of PD-L1 and TMB has been demonstrated in gastroesophageal adenocarcinoma (GEA) in response to systemic chemotherapy. With the increased use of hyperthermic intraperitoneal chemotherapy (HIPEC) for GEA peritoneal metastases (PM), we aimed to determine the effects of HIPEC on genomic heterogeneity of PM. Methods: This is a retrospective review of a prospectively maintained database of patients with stage IV GEA who underwent iterative laparoscopic HIPEC (mitomycin C 30 mg + cisplatin 200 mg, 60 minutes) between 2017 and 2021. PD-L1 status and TMB levels were reviewed from peritoneal tumor specimens collected prior to each HIPEC. PD-L1 status was defined as positive if combined positive score (CPS) was 1 or greater using the 22C3 pharmDx assay. TMB levels were defined as low, intermediate, or high for up to 5, 5 to 15, or over 15 mutations per megabase (m/MB), respectively. Potentially actionable and biologically relevant variants were reviewed, as well as overall survival, defined as time from diagnosis with stage IV disease to death from any cause. Results: 16 patients completed at least one HIPEC during the study period. Median age was 55.5 years (range 43-79), 50% were female, and 62.5% were Caucasian. All patients received at least one line of systemic chemotherapy after stage IV diagnosis and prior to first HIPEC. Median peritoneal cancer index at first HIPEC was 15 (range 3-39). Three patients completed only one HIPEC. Of the 13 who completed at least two HIPECs, 5 had sufficient tumor tissue for genomic analysis at two timepoints. Of those 5 patients, one exhibited a change in PD-L1 expression from positive to negative after HIPEC, and one exhibited an increase in TMB from low to intermediate. All 5 patients exhibited a change in the profile of potentially actionable or biologically relevant genetic variants, including gain or loss of mutations in DNA repair genes (RAD51), proto-oncogenes (MET), and tumor suppressor genes (ERBB3, IRS2). Median overall survival amongst the full cohort was 27.4 months, with median follow-up of 26.1 months. Overall survival was higher amongst those who underwent at least 2 HIPECs compared to only one, but this was not statistically significant. Conclusions: Amongst our cohort, only one patient exhibited a change in PD-L1 expression and one in TMB after HIPEC. However, HIPEC was associated with a change in genetic variant profiles in all evaluable patients. If confirmed in larger studies, this temporal genomic heterogeneity could inform the role of PD-L1, TMB, and other genetic variants as predictive biomarkers for therapy after HIPEC. Iterative laparoscopic HIPEC warrants further investigation as a treatment option after systemic therapy for GEA with peritoneal metastases.

Hyperthermic Intraperitoneal Chemotherapy (HIPEC) in the Management of Advanced Ovarian Cancer. A Literature Review

The rationale behind the use of hyperthermic intraperitoneal chemotherapy (HIPEC) after cytoreductive surgery is the association between pharmacological activity of chemotherapy delivered to the peritoneal cavity with the enhanced cytotoxic effect of hyperthermia. Data on the efficacy of HIPEC in the primary debulking surgery (PDS) setting are still controversial and limited by the small sample size of most of the studies, the inclusion of different treatment settings and chemotherapy regimens. Among the ongoing prospective trials, only the OVHIPEC-2 trial is investigating exclusively patients submitted to PDS ± HIPEC with cisplatin 100 mg/m22 and results are expected by 2026. On the interval debulking surgery (IDS) setting high quality data are coming from the result of the OVHIPEC-1 trial, which demonstrated a survival advantage of nearly 4 months in median progression-free survival (PFS) (14.2 months vs. 10.7 months; p = 0.003) and almost 12 months in median overall survival (OS) (45.7 months vs. 33.9 months; p = 0.02) for HIPEC treated patients (cisplatin 100 mg/m22) compared to no-HIPEC group, with comparable morbidity. However, due to some criticisms raised to the results of OVHIPEC-1 trial, the ESMO-ESGO guidelines recommended not to consider HIPEC as standard therapy until results from ongoing randomized control trials (RCTs) are provided. On the contrary, for the National Comprehensive cancer network (NCCN) guidelines HIPEC can be considered at the time of IDS. Similarly, data supporting the role of HIPEC in association with surgery in case of recurrent disease appear to be controversial in terms of patients and selection and intraperitoneal chemotherapy regimen. Indeed, despite the positive results coming from a prospective randomized trial, they appear to be biased by the inclusion of both platinum sensitive and resistant disease and the lack of information on PFS. Those results are in contrast with data coming from another prospective trial, which failed to demonstrate a survival gain of recurrent ovarian cancer patients treated with secondary cytoreductive surgery + HIPEC with carboplatin (800 mg/m22 for 90 min) compared to women submitted to cytoreduction only. Again, in this subgroup of patients data of ongoing RCTs are awaited to assess the impact on survival of HIPEC administration in case of recurrent disease.

Some features of intraoperative infusion-transfusion therapy when performing cytoreductive operations with the use of hyperthermic intraperitoneal chemotherapy in patients with ovarian cancer: retrospective cohort study

Introduction. Сytoreductive operations with using hyperthermic intraoperative intraperitoneal chemotherapy(CR + HIPEC) is an effective technology in the treatment of locally advanced and metastatic ovarian cancer, the relevance of the treatment of this one’s is beyond doubt. The neсessity of protection organs and systems of the body from a stress response, correction of water and electrolyte balance, blood loss, volemia, and prevention of the toxic effects of chemotherapy make infusion-transfusion therapy (ITT) one of the main components of anesthesia during such operations. Objectives. An analyze the qualitative and quantitative composition of perioperative infusion-transfusion therapy in patients with advanced stages of ovarian cancer during cytoreductive operation with the addition of HIPEC of the abdominal cavity. Materials and methods. In retrospective study 84 patients, 2 types of surgical interventions and anesthetic accompaniment were analyzed, depending on the availability of HIPEC. The duration of the anesthetic treatment, the doses of the anesthetics, the volume of blood loss, the volume and quality of intraoperative infusion therapy were assessed. Results. With ITT carried out with cytoreduction using GIIH, the volume of administration of crystalloid solutions increases by 2.3 times; the average value of the infusion volume increases by 16 (10,5–20) ml/kg/hour. When analyzing the proportional ratio of crystalloid and colloidal solutions, their qualitative composition with CR + GIIH consists of: erythrocyte suspension 3.1 %, FFP 13.6 %, colloidal solutions 8.52 %, crystalloid solutions 74.6 % of total infusion’s volume. Conclusions. Perioperative ITT performed with cytoreduction using GIIH differs significantly from ITT without that. The necessity for high-volume infusion-transfusion therapy by increasing the introduction of crystalloids during cytoreductive operations with hyperthermic intraoperative intraperitoneal chemotherapy was revealed. This technique had no complications and allowed maintaining the stability of hemodynamics, volumetric volume and the required volume of diuresis. The use of a “balanced electrolyte solution” is preferable for intraoperative high-volume ITT.

Free cancer cells in gastric cancer - methods of detection, clinical and prognostic importance (meta-analysis).

Gastric cancer (GC) is one of the most common malignant cancers worldwide. Intraperitoneal dissemination is the typical mechanism of the formation of metastases in GC. The diagnosis of the presence of intraperitoneal free cancer cells (IFCCs) is treated equally to the M (metastasis) category according to the 8th edition of the TNM classification by the American Joint Committee on Cancer. IFCCs are cells which have detached from the primary tumour through exfoliation into the peritoneal cavity. The source of IFCCs may be iatrogenic due to improper surgical technique during resection of the tumour and may lead to intraperitoneal dissemination. Cytological examination of peritoneal lavage is considered as a gold standard in the confirmation of the presence of IFCCs; however, its sensitivity is very low. In order to increase the sensitivity and reliability of the examination, molecular biology techniques should be applied. In the case of detection of the presence of IFCCs in patients with GC, the patient should be qualified for chemotherapy, or possibly the use of hyperthermic intraperitoneal chemotherapy should be considered.

Selection of patients with ovarian cancer who may show survival benefit from hyperthermic intraperitoneal chemotherapy: A systematic review and meta-analysis.

The use of hyperthermic intraperitoneal chemotherapy (HIPEC) after cytoreductive surgery has been extensively studied in patients with peritoneal carcinomatosis from various malignancies. However, the effectiveness of HIPEC for ovarian cancer is still controversial. Therefore, we performed this meta-analysis to identify patients with ovarian cancer who can obtain survival benefit from HIPEC. Articles regarding HIPEC in the MEDLINE, EMBASE, and Cochrane Library were searched till December 2018. In total, 13 case-control studies and two randomized controlled trials were included in this meta-analysis. We investigated the effect of HIPEC on disease-free survival (DFS) and overall survival (OS), and performed subgroup analyses based on the study design, adjustment of confounding variables, and quality of the study. HIPEC improved both DFS (hazard ratio [HR], 0.603; 95% confidence interval [CI], 0.513-0.709) and OS (HR, 0.640; 95% CI, 0.519-0.789). In cases of primary disease, HIPEC improved DFS (HR, 0.580; 95% CI, 0.476-0.706) and OS (HR, 0.611; 95% CI, 0.376-0.992). Subgroup analyses revealed that HIPEC did not improve OS but improved DFS of patients with residual tumors ≤1 cm or no visible tumors. In cases of recurrent disease, HIPEC was associated with better OS (HR, 0.566; 95% CI, 0.379-0.844) but not with DFS. Subgroup analyses also revealed similar tendencies. However, HIPEC improved DFS of patients with residual tumors ≤1 cm or no visible tumors, while it improved OS of only those with residual tumors ≤1 cm. HIPEC may improve DFS of patients with ovarian cancer when residual tumors were ≤1 cm or not visible. It may also improve OS of only patients with recurrent disease whose residual tumors were ≤1 cm.

Role of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in the treatment of gastric cancer.

Patients with peritoneal carcinomatosis (PC) of gastric origin have a poor prognosis of life with an average survival of 1-3 months. Systemic chemotherapy has improved the survival of those patients with gastric metastatic cancer at 7-10 months. However, this benefit could not be reproduced in those patients with PC. The current literature for the use of hyperthermic intraperitoneal chemotherapy (HIPEC) for gastric PC has significant variation related to patient selection, treatment intent (palliative vs. attempt at curative treatment), surgical technique, intraperitoneal chemotherapy agent utilized, and systemic chemotherapy administered adjuvantly. From the perspective of patient selection for cytoreduction and HIPEC, patients with extensive PC are not candidates. In addition, unresectable location would make a patient a poor candidate for cytoreduction and HIPEC. Optimally, those with positive peritoneal cytology alone could benefit most. However, the role of cytoreductive surgery and HIPEC in patients with PC of gastric origin has not yet been clarified.

Statement of the AGO Kommission Ovar, AGO Study Group, NOGGO, AGO Austria and AGO Switzerland Regarding the Use of Hyperthermic Intraperitoneal Chemotherapy (HIPEC) in Ovarian Cancer

The AGO Kommission Ovar already published a statement in 2013, warning about the uncritical use of hyperthermic intraperitoneal chemotherapy (HIPEC) outside controlled studies. This statement has now been updated after the most recent literature was reviewed by AGO Kommission Ovar, the AGO Study Group, NOGGO, AGO Austria and AGO Switzerland. The authors conclude that HIPEC remains experimental. Its use is not recommended and should be rejected outside of prospective controlled trials.

Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Pseudomyxoma Peritonei and Appendix Tumours.

Pseudomyxoma peritonei (PMP) is the intra-peritoneal accumulation of mucus due to mucinous neoplasia, most often from a ruptured mucinous appendiceal neoplasm. A similar syndrome is caused by appendix cancer and other gastrointestinal malignancies. Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) provides long-term survival in selected patients with these conditions. The management of the appendiceal neoplasm prior to development of peritoneal involvement is initially discussed. This is followed by an overview of the management of peritoneal disease caused by appendiceal neoplasms. The principles and basic techniques of CRS and intraperitoneal chemotherapy (both intraoperative and post operative) are then discussed. Survival outcomes from several large studies are summarised. Prognostic factors are also discussed. We report our basic outcome data for the 345 patients with PMP or appendix cancer treated at our institution. Finally, the promising upcoming treatment of mucolytic therapy is discussed. We conclude that appendiceal neoplasms, although rare can cause significant morbidity and mortality. With optimal management long-term survival is possible in the majority of patients. The key to treatment is complete cytoreduction and use of hyperthermic intraperitoneal chemotherapy.

Su1740 30-Day Mortality After Emergency Surgery for Colorectal Cancer: Who Is At Risk?

Introduction: Peritoneal carcinomatosis denotes extensive tumour involvement of the peritoneum, and is often regarded as terminal. There has been a paradigm shift in treatment, with the application of cytoreductive surgery combined with intra-peritoneal chemotherapy. The extensive nature of the surgery and malignancy-associated hypercoagulable state should increase the risk of PE, which can further increase morbidity and/or mortality. Incidence and risk factors for pulmonary embolism (PE) in this population have not been investigated in detail. Aims: To establish the incidence and specific operative risk factors for developing PE in patients with peritoneal carcinomatosis post peritonectomy and peri-operative intraperitoneal chemotherapy. Methods: A cohort of 596 patients that underwent cytoreductive surgery (peritonectomy) over a 12-year period was identified using the prospective database from St George Hospital Peritonectomy Unit. A case-control study was undertaken whereby cases were defined by the development of PE within 60 days of peritonectomy. A diagnosis of PE was based on computed tomography pulmonary angiography confirmation. The prospective database was reviewed to obtain the following clinical information for both cases (with PE) and controls (without PE): length of surgery, use of hyperthermic intraperitoneal chemotherapy (HIPEC) and early postoperative intraperitoneal chemotherapy (EPIC), peritoneal carcinomatosis index (PCI) and number of intraoperative blood transfusions. Results: The mean age of the cohort was 52.7 ± 13.1 years, with no significant difference in the ages of cases or controls; 43.3% were male and 56.7% were female. Primary malignancies in these patients were pseudomyxoma peritonei, appendiceal, ovarian or colorectal cancer, and mesothelioma. Out of the 596 patient cohort, 34 were identified as having PE post cytoreductive surgery (5.7%). When compared to controls, the PE group had longer mean operative time of 10.4 ± 2.8 hours vs 8.9 ± 3.1 hours (p=0.01) and higher mean PCI values at 23 ± 12 vs 18 ± 11 (p=0.02). An operative time of more >9 hours increased the risk of developing PE (OR 3.3, 95% CI 1.41-7.72, p=0.006) as did having a PCI of >20 (OR 2.4, 95% CI 1.18-4.9, p=0.02). There was no difference in mean transfusion requirements (6.6 vs 6.0; p=0.67). No significant association was found between HIPEC and development of PE (x2=2.87, 1 df, P=0.9) or EPIC and subsequent PE (x2=0.001, 1 df, P=1). Conclusions: There is a relatively high incidence of pulmonary embolism in patients following cytoreductive surgery for peritoneal carcinomatosis. Patients at highest risk of developing PE postoperatively are those with PCI of more than 20 and those who have operations lasting more than 9 hours. Peri-operative chemotherapy and blood transfusions are not risk factors for PE.

Su1739 Risk Factors for Pulmonary Embolism Following Cytoreductive Surgery and Intraperitoneal Chemotherapy for Peritoneal Carcinomatosis

Introduction: Peritoneal carcinomatosis denotes extensive tumour involvement of the peritoneum, and is often regarded as terminal. There has been a paradigm shift in treatment, with the application of cytoreductive surgery combined with intra-peritoneal chemotherapy. The extensive nature of the surgery and malignancy-associated hypercoagulable state should increase the risk of PE, which can further increase morbidity and/or mortality. Incidence and risk factors for pulmonary embolism (PE) in this population have not been investigated in detail. Aims: To establish the incidence and specific operative risk factors for developing PE in patients with peritoneal carcinomatosis post peritonectomy and peri-operative intraperitoneal chemotherapy. Methods: A cohort of 596 patients that underwent cytoreductive surgery (peritonectomy) over a 12-year period was identified using the prospective database from St George Hospital Peritonectomy Unit. A case-control study was undertaken whereby cases were defined by the development of PE within 60 days of peritonectomy. A diagnosis of PE was based on computed tomography pulmonary angiography confirmation. The prospective database was reviewed to obtain the following clinical information for both cases (with PE) and controls (without PE): length of surgery, use of hyperthermic intraperitoneal chemotherapy (HIPEC) and early postoperative intraperitoneal chemotherapy (EPIC), peritoneal carcinomatosis index (PCI) and number of intraoperative blood transfusions. Results: The mean age of the cohort was 52.7 ± 13.1 years, with no significant difference in the ages of cases or controls; 43.3% were male and 56.7% were female. Primary malignancies in these patients were pseudomyxoma peritonei, appendiceal, ovarian or colorectal cancer, and mesothelioma. Out of the 596 patient cohort, 34 were identified as having PE post cytoreductive surgery (5.7%). When compared to controls, the PE group had longer mean operative time of 10.4 ± 2.8 hours vs 8.9 ± 3.1 hours (p=0.01) and higher mean PCI values at 23 ± 12 vs 18 ± 11 (p=0.02). An operative time of more >9 hours increased the risk of developing PE (OR 3.3, 95% CI 1.41-7.72, p=0.006) as did having a PCI of >20 (OR 2.4, 95% CI 1.18-4.9, p=0.02). There was no difference in mean transfusion requirements (6.6 vs 6.0; p=0.67). No significant association was found between HIPEC and development of PE (x2=2.87, 1 df, P=0.9) or EPIC and subsequent PE (x2=0.001, 1 df, P=1). Conclusions: There is a relatively high incidence of pulmonary embolism in patients following cytoreductive surgery for peritoneal carcinomatosis. Patients at highest risk of developing PE postoperatively are those with PCI of more than 20 and those who have operations lasting more than 9 hours. Peri-operative chemotherapy and blood transfusions are not risk factors for PE.

Hyperthermic Intraperitoneal Chemotherapy in Ovarian Cancer

An analysis of experience of surgical and gynecologic oncologists in the United States with the use of hyperthermic intraperitoneal chemotherapy for women with invasive epithelial ovarian cancer (EOC). An Internet-based registry (HYPER-O) collected data from collaborating institutions. Eligibility included women with EOC treated with hyperthermic intraperitoneal chemotherapy. Borderline and nonepithelial cancers were excluded. As of July 1, 2008, 141 women were eligible for analysis treated at the following time points: frontline (n = 26), interval debulking (n = 19), consolidation (n = 12), and recurrence (n = 83). The mean perfusion temperatures were 38.5 to 43.6 degrees C (median, 41.9 degrees C) for inflow and 36.9 to 42.9 degrees C (median, 41 degrees C) for outflow for 30 to 120 minutes. Treatment was with a platinum agent (n = 72), mitomycin (n = 53), or a combination (n = 14). Median follow-up was 18 months (range, 0.3-140.5 months) and median overall survival 30.3 months (95% confidence interval, 23.0-37.6) with 2-, 5-, and 10-year overall survival probabilities of 49.1%, 25.4%, and 14.3%, respectively. Of the 141 patients, 110 (78%) experienced recurrence of ovarian cancer and 87 died, 3 (0.5%) dying within 30 days of surgery. In the multivariable analysis, the factors significant for increased survival were sensitivity to platinum response (P = 0.048), completeness of cytoreduction scores of 1 or 0 (P = 0.025), carboplatin alone or a combination of 2 or more chemotherapy agents used (P = 0.011), and duration of hospital stays of 10 days or less (P = 0.021). Hyperthermic intraperitoneal chemotherapy is a viable additional treatment option for patients with invasive EOC and may extend life in selected groups. It warrants further study in randomized controlled trials.