Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is an innovative approach for treating peritoneal carcinomatosis that applies chemotherapeutic drugs into the peritoneal cavity as an under-pressure airflow. It improves local bioavailability of cytostatic drugs as compared to conventional intraperitoneal chemotherapy. The aim of this study is to prove feasibility, efficacy and safety of this new treatment. Patients included in the analysis underwent at least two single port PIPAC procedures; drugs used were Oxaliplatin for colorectal cancers and Cisplatin + Doxorubicin for ovarian, gastric, and primary peritoneal cancers. The primary endpoint was the Disease Control Rate according to the RECIST (Response Evaluation Criteria in Solid Tumors) criteria. Secondary significant endpoints were overall and progression free survival, tumor regression on histology, and quality of life. Safety and tolerability were assessed according to the Common Terminology Criteria for Adverse Events 4. Sixty-three patients were enrolled in this trial. Forty patients (100 PIPAC) were eligible for analysis. Twenty patients were undergoing systemic chemotherapy. Fourteen patients reported an objective response (35%). Median overall survival was 18.1 months; median progression-free survival was 7.4 months. Minor morbidity was observed in seven procedures. Grade 3 complications occurred in two patients, and grade 4 in one patient submitted to reoperation. Single-port PIPAC is feasible, safe, and easy to perform. The combined treatment based on systemic chemotherapy and PIPAC does not induce significant hepatic and renal toxicity and can be considered a valid therapeutic option in patients with advanced peritoneal disease. Further studies on the use of PIPAC alone, possibly with different drug dosages, may define the real effectiveness of the procedure.

Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) is an innovative laparoscopic intraperitoneal chemotherapy approach with the advantage of a deeper tissue penetration. Thus far, oxaliplatin has been administered at an arbitrary dose of 92 mg/m2, cisplatin at 7.5 mg/m2 and doxorubicin 1.5 mg/m2. This is a model-based approach phase I dose escalation study with the aim of identifying the maximum tolerable dose of the three different drugs. The starting dose of oxaliplatin was 100 mg/m2; cisplatin was used in association with doxorubicin: 15 mg/m2 and 3 mg/m2 were the respective starting doses. Safety was assessed according to Common Terminology Criteria for Adverse Events (CTCAE version 4.03). Thirteen patients were submitted to one PIPAC procedure. Seven patients were treated with cisplatin and doxorubicin and 6 patients with oxaliplatin; no dose limiting toxicities and major side effects were found. Common adverse events included postoperative abdominal pain and nausea. The maximum tolerable dose was not reached. The highest dose treated cohort (oxaliplatin 135 mg/m2; cisplatin 30 mg/m2 and doxorubicin 6 mg/m2) tolerated PIPAC well. Serological analyses revealed no trace of doxorubicin at any dose level. Serum levels of cis- and oxaliplatin reached a peak at 60–120 min after PIPAC and were still measurable in the circulation 24 h after the procedure. Cisplatin and doxorubicin may be safely used as PIPAC at a dose of 30 mg/m2 and 6 mg/m2, respectively; oxaliplatin can be used at an intraperitoneal dose of 135 mg/m2. The dosages achieved to date are the highest ever used in PIPAC.

Background:Pressurized IntraPeritoneal Aerosol Chemotherapy (PIPAC) is a drug delivery system for treatment of peritoneal metastasis (PM). A limitation of this technique is the non-access rate (10-15 %) due to peritoneal adhesions. The aim of the study was to assess feasibility and safety of the single-port access technique for PIPAC. Methods: Single-center, pilot study. Case series, retrospective analysis on 17 patients with PM of various origin treated with intraperitoneal cisplatin, doxorubicin and/or oxaliplatin administered as PIPAC. Single-port access was attempted in all patients by minilaparotomy. Results: Twenty-nine PIPAC procedures were performed. Nine patients were subjected to 1 PIPAC, four patients to 2 PIPAC and four patients to 3 PIPAC. Access to peritoneal cavity was possible in all cases. There was no bowel access lesion. Tightness of the abdomen (CO 2 -flow = 0) was achieved in all cases. No postoperative complications according to CTCAE (Common Terminology Criteria for Adverse Events) > 2 were observed, no re-laparotomies required and no postoperative mortality recorded. Conclusions: Single port-access is feasible and safe for PIPAC. Potential advantages over multiple trocars technique are a lower non-access rate, a lower risk of bowel lesions and a better tightness of the abdomen. This has now to be confirmed in a comparative study.

In recent years, cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) have substantially improved the clinical outcome of pseudomyxoma peritonei (PMP) originating from mucinous appendiceal cancer. However, current histopathological grading of appendiceal PMP frequently fails in predicting disease outcome. We recently observed that the integration of cancer cell transcriptional traits with those of cancer-associated fibroblasts (CAFs) improves prognostic prediction for tumors of the large intestine. We therefore generated global expression profiles on a consecutive series of 24 PMP patients treated with CRS plus HIPEC. Multiple lesions were profiled for nine patients. We then used expression data to stratify the samples by a previously published “high-risk appendiceal cancer” (HRAC) signature and by a CAF signature that we previously developed for colorectal cancer, or by a combination of both. The prognostic value of the HRAC signature was confirmed in our cohort and further improved by integration of the CAF signature. Classification of cases profiled for multiple lesions revealed the existence of outlier samples and highlighted the need of profiling multiple PMP lesions to select representative samples for optimal performances. The integrated predictor was subsequently validated in an independent PMP cohort. These results provide new insights into PMP biology, revealing a previously unrecognized prognostic role of the stromal component and supporting integration of standard pathological grade with the HRAC and CAF transcriptional signatures to better predict disease outcome.