Appraisal of peritoneal cavity’s capacity in order to assess the pharmacology of liquid chemotherapy solution in hyperthermic intraperitoneal chemotherapy

Background  

Cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (HIPEC) is an aggressive strategy to treat patients presenting peritoneal carcinomatosis from various origins. The aim of this study was to evaluate the correlation between the peritoneal cavity’s capacity and the weight, the size and the body mass index (BMI) of patients to see if it would be relevant to adapt the pharmacology of HIPEC based on these factors.     

Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) for Persistent and Recurrent Advanced Ovarian Carcinoma: A Multicenter, Prospective Study of 246 Patients

Background

Epithelial ovarian carcinoma is the main cause of death from gynaecological cancers in the western world. The initial response rate to the frontline therapy is high. However, the prognosis of persistent and recurrent disease remains poor. During the two past decades, a new therapeutic approach to peritoneal carcinomatosis has been developed, combining maximal cytoreductive effort with hyperthermic intraperitoneal chemotherapy (HIPEC).

Methods

A retrospective, multicentric study of 246 patients with recurrent or persistent ovarian cancer, treated by cytoreductive surgery and HIPEC in two French centers between 1991 and 2008, was performed.

Results

An optimal cytoreductive surgery was possible in 92.2?% of patients. Mortality and morbidity rates were 0.37?% and 11.6?%, respectively. The overall median survival was 48.9?months. There was no significant difference in overall survival in patients with persistent or recurrent disease. In multivariate analysis, performance status was a significant prognostic factor in patients with extensive peritoneal carcinomatosis (peritoneal cancer index >10).

Conclusions

Salvage therapy combining optimal cytoreductive surgery and HIPEC is feasible and may achieve long-term survival in highly selected patients with recurrent ovarian carcinoma, including those with platinum resistant disease, with acceptable morbidity.     

Intraperitoneal Cytokine Level in Patients with Peritoneal Surface Malignancies. A Study of the RENAPE (French Network for Rare Peritoneal Malignancies)

Background

Prognosis of peritoneal surface malignancies is influenced by the adequacy of surgical and chemotherapeutic treatment and by tumor spread at the time of diagnosis. By promoting morphological changes in the mesothelium, inflammatory cytokines reflect tumor biology and could be evaluated as biomarkers. Our objective was to evaluate intraperitoneal levels of IL-6, IL-8, IL-10, TNF-alpha, and sICAM in patients with pseudomyxoma peritonei and peritoneal mesothelioma.

Methods

Serum and peritoneal fluid samples were prospectively collected in patients managed for peritoneal surface malignancies including pseudomyxoma peritonei (PMP), mesotheliomas, and other rare primitive peritoneal cancers (cancer group) and patients who underwent intraperitoneal laparoscopic surgical procedures for benign diseases (noncancer group). Samples were analyzed for IL-6, IL-8, IL-10, TNF-alpha, and sICAM concentrations. Correlations were assessed with tumor spread related clinical scores.

Results

In both patient groups, intraperitoneal cytokine levels were higher than serum levels. Cancer patients had significantly higher intraperitoneal cytokine levels than noncancer patients. Peritoneal levels tended to increase in cancer patients with free tumor cells in peritoneal fluid. They were significantly higher in patients with tumor implants ≥2 cm and/or patients with peritoneal carcinomatosis index (PCI) >19. Furthermore, patients with malignant pseudomyxoma peritonei (grades II and III) had higher levels than patients with nonmalignant disease (grade I).

Conclusions

Assessment of intraperitoneal IL-6, IL-8, IL-10, TNF-alpha, and sICAM levels can be performed in patients with peritoneal surface malignancies. They can be considered as both diagnostic and prognostic biomarkers that could be used as useful adjuncts for therapeutic decision making.     

Cytoreductive surgery and HIPEC after neoadjuvant chemotherapy for advanced epithelial ovarian cancer

AIM: To reduce postoperative complications and to make possible an optimal cytoreduction, neoadjuvant chemotherapy (NACT) followed by interval debulking surgery has been applied with encouraging results. METHODS: Between December 2009 and February 2012, patients with stage IIIC-IV epithelial ovarian cancer (EOC) underwent diagnostic laparoscopy, to assess the feasibility of optimal debulking surgery. The modified Fagotti score was applied to assess the feasibility of resection with zero residual tumor. Patients who were not candidate for upfront debulking surgery were submitted to NACT, then reassessed according to the RECIST 1.1 criteria and submitted to cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) if they showed clinical response or stable disease. The remaining cycles of adjuvant systemic chemotherapy (ASCT) were administered postoperatively, to complete 6 cycles of systemic chemotherapy. RESULTS: Nine patients were included. Clinical response to NACT was complete in 3 patients and partial in 5 patients; one patient had stable disease. All patients underwent CRS resulting in CC0 disease prior to HIPEC. Average operative time was 510 min. Average intensive care unit stay was 2 d. Average postoperative hospital stay was 25 d. No postoperative mortality was observed. One patient experienced pelvic abscess. One patient refused ASCT. The remaining 8 patients started ASCT. Average time to chemotherapy was 36 d. All patients are alive, with an average follow up of 11 mo. Eight patients are disease-free at follow up. CONCLUSION: HIPEC after CRS for advanced EOC is feasible with acceptable morbidity and mortality. NACT may increase the chance for achieving complete cytoreduction. Phase 3 studies are needed to determine the effects of HIPEC on survival.     

Estimation of the cost of treatment by chemotherapy for early breast cancer in Morocco

Background

Physical inactivity is a major risk factor for many chronic diseases including diabetes, cardiovascular diseases and some cancers. It is estimated that, in Australia, physical inactivity contributes to 13,500 annual deaths and incurs an annual cost of AU$ 21 billion to the health care system. The cost of physical inactivity to the Western Australian (WA) economy is estimated to be about AU$ 2.1 billion. Increased burden of physical inactivity has motivated health professionals to seek cost effective intervention to promote physical activity. One such strategy is encouraging general practitioners (GPs) to advocate physical activity to the patients who are at high risk of developing chronic diseases associated with physical inactivity. This study intends to investigate the cost-effectiveness of a subsidy program for GP advice to promote physical activity.

Methodology

The percentage of population that could potentially move from insufficiently active to sufficiently active, on GP advice was drawn from the Western Australian (WA) Premier's Physical Activity Taskforce (PATF) survey in 2006. Population impact fractions (PIF) for diseases attributable to physical inactivity together with disability adjusted life years (DALYs) and health care expenditure were used to estimate the net cost of intervention for varying subsidies. Cost-effectiveness of subsidy programs were evaluated in terms of cost per DALY saved at different compliance rates.

Results

With a 50% adherence to GP advice, an annual health care cost of AU$ 24 million could be potentially saved to the WA economy. A DALY can be saved at a cost of AU $ 11,000 with a AU$ 25 subsidy at a 50% compliance rate. Cost effectiveness of such a subsidy program decreases at higher subsidy and lower compliance rates.

Conclusion

Implementing a subsidy for GP advice could potentially reduce the burden of physical inactivity. However, the cost-effectiveness of a subsidy program for GP advice depends on the percentage of population who comply with GP advice.