Volume 4, Issue 2 -

Background The randomized trial PRODIGE 7 failed to show the benefit of oxaliplatin hyperthermic intraperitoneal chemotherapy (HIPEC) in colorectal peritoneal metastasis treatment (CR PM). This systematic review focuses on the association of cisplatin (CDDP) with mitomycin C (MMC) in HIPEC in CR PM. Content Experimental studies demonstrated that hyperthermia, in addition to CDDP ± MMC treatment, gradually improved the cytotoxic effect by increasing early apoptosis, eATP interaction, intracellular CDDP concentration (by 20%) and p73 expression. Recent studies with highly selected patients reported unusual prolonged survival with a median overall survival (OS) of approximately 60 months, with a HIPEC combination of CDDP (25 mg/m 2 /L) plus MMC (3.3 mg/m 2 /L) at a temperature of 41.5–42.5 °C for 60–90 min. Major complications occurred in less than 30% of patients with limited hematological toxicity (less than 15%). In addition, in a phase 2 trial, an adjuvant HIPEC benefit was demonstrated in colorectal cancer patients with high risk for peritoneal failure (5-year OS: 81.3% vs. 70% for the HIPEC group vs. the control group, respectively, p=0.047). After a recurrence, an iterative procedure permitted similar recurrence-free disease (13 vs. 13.7 months) with an acceptable morbidity (18.7% of severe complications). Summary and outlook The combination of CDDP and MMC seems to be an interesting protocol as an alternative to high-dose and short-term oxaliplatin.

Background The primary treatment for advanced ovarian cancer is aggressive cytoreductive surgery (CRS), which is associated with considerable morbidity. The aim of this meta-analysis is to compare morbidity associated with primary CRS and secondary CRS for recurrent disease. Methods A literature search was performed using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines for publications reporting morbidity and mortality in patients undergoing CRS in primary and recurrent ovarian malignancy. Embase, Medline, Pubmed, Pubmed Central, clinicaltrials. gov and Cochrane databases were searched. Two independent reviewers applied inclusion and exclusion criteria to select included papers. A total of 215 citations were reviewed; 6 studies comprising 641 patients were selected for the analysis. Results Results were reported as mean differences or pooled odds ratios (OR) with 95 % confidence intervals (95 % CI). The overall morbidity rate was 38.4 %, and this did not differ between the two groups (p=0.97). This did not change when only Clavien-Dindo grade 3 and 4 morbidities were accounted for (14 % primary CRS, 15 % recurrent, p=0.83). Compared to primary CRS, secondary CRS was associated with a similar operative time (mean 400 min, I2=79 %, p=0.45), rate of bowel resection (I2=75 %, p=0.37) and transfusion requirements (MD – 0.7 L, I2=76 %, p=0.45). The mortality rate in both groups was too low to allow for meaningful meta-analysis, with four deaths in the group undergoing primary cytoreductive surgery (1.0 %) and two deaths in the group with recurrent disease (0.9 %). Conclusions In conclusion, secondary CRS for recurrent ovarian cancer is a safe and feasible option in carefully pre-selected patients with comparable morbidity to primary CRS.

Background Malignant peritoneal mesothelioma (MPM) is a rare tumoral disease characterized by the diffuse involvement of the peritoneal serosa. The standard frontline treatment of MPM is cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (HIPEC) unless the peritoneal disease is considered unresectable. For unresectable patients the standard frontline treatment is a combination of cisplatin and pemetrexed but the prognosis remains ominous with only 13 months of overall survival (OS). Methods The proposed study is a multicenter randomized non-comparative study evaluating the association of Pressurized Intra-Peritoneal Aerosol Chemotherapy (PIPAC) and systemic chemotherapy vs. systemic chemotherapy alone as first-line treatment of MPM. Patients will be randomized with a 2:1 ratio using a minimization technique. Sixty-six patients have to be enrolled. Stratification will be performed according to histology (epithelioid vs. sarcomatoid and biphasic), presence of extraperitoneal disease and center. Primary objective is OS and secondary objectives include progression-free survival (PFS), safety, compliance, feasibility, conversion to resectability, histological response to treatment and quality of life. Conclusions We expect to show that intensification of the first line treatment with PIPAC for initially unresectable MPM patients increases OS. Trial registration Prospective study. Clinicaltrials.gov: NCT03574493 EudraCT: 2019–001515-23.

Background This case report aims to describe the impact of the bidirectional chemotherapy (BDC) on resecability for initially unresectable malignant peritoneal mesothelioma (MPM). Methods We report a case of 55-year-old male with the diagnosis of initially unresecable MPM. The BDC combined intravenous (IV) chemotherapy (Cisplatin–Pemetrexed) and intra peritoneal (IP) chemotherapy (Cisplatin). The response to chemotherapy was assessed by CT – scan and laparoscopy. Results Initial evaluation classed the disease as unresecable with PCI at 39. At the reevaluation, CT – scan and laparoscopy showed a macroscopic response, allowing surgery consisting of cytoreductive surgery and hyperthermic intra peritoneal chemotherapy (Doxorubicin and Cisplatin). Conclusions BDC (IV and IP) has promising results and allows to undergo surgery for selected patients with borderline or initially unresectable MPM.