Pressurized Intraperitoneal Aerosol Chemotherapy Procedure Research Articles

The scientific report from the first pressurized intraperitoneal aerosol chemotherapy (PIPAC) procedures performed in the eastern part of Central Europe.

ObjectiveTo perform a single-centre, detailed analysis of the preparations for the introduction of the first pressurized intraperitoneal aerosol chemotherapy (PIPAC) programme in the eastern part of Central Europe.MethodsThe study analysed the 14-month preparation period prior to the performance of the first PIPAC procedure with respect to: (i) general preparations; (ii) patient referral and qualification; (iii) the first PIPAC procedure; (iv) the 2 weeks following PIPAC programme establishment; and (v) general problematic issues that arose.ResultsThe length of time needed to prepare our institution for the first PIPAC procedure was extremely long compared with other European Union PIPAC centres: 14 months versus a standard 3–6 months of preparation. The longest amount of time (12 months) was required to prepare the required paperwork.ConclusionsA new PIPAC programme was successfully established in the eastern part of Central Europe. The length of time to implement this method was significantly longer because of lengthy bureaucratic processes. These current findings should help new centres, especially in this part of Europe, to establish a PIPAC programme more quickly.

Occupational exposure to platinum drugs during intraperitoneal chemotherapy. Biomonitoring and surface contamination

BackgroundHyperthermic intraperitoneal chemotherapy (HIPEC) has been introduced over the last decade for the treatment of peritoneal carcinomatosis. In this procedure, heated cytotoxic drugs are administered directly into the abdominal cavity, ensuring cancer cells to be exposed while reducing systemic toxicity. More recently, pressurized intraperitoneal aerosol chemotherapy (PIPAC), where the chemotherapeutic drug is injected into the peritoneal cavity as an aerosol under pressure, has been proposed to patients in palliative situation, as a new approach. The amount of drug used is up to 10 fold lower than in HIPEC. The use of cytotoxic drugs poses an occupational risk for the operating room personnel. This study investigated the potential exposure of the medical staff by biomonitoring and surface contamination measurements, during a HIPEC procedure and a PIPAC procedure. MethodWipe samples were collected from various locations in operating rooms including gloves, hands, devices and floor. Urines samples were collected from 10 volunteers of the medical staff and from a control group. The platinum analysis was performed by inductively coupled plasma mass spectrometry. ResultsSignificant contaminations were observed on the floor, gloves, shoes and devices. However, urinary platinum was below the limit of quantification (<10 ng/L) for more than 50% of samples from the healthcare workers performing HIPEC and PIPAC. Concentrations did not differ significantly from those reported for the control group. ConclusionThere appears to be little risk of exposure to platinum drugs during HIPEC and PIPAC providing the adequate safety measures are implemented.

Multicenter comprehensive methodological and technical analysis of 832 pressurized intraperitoneal aerosol chemotherapy (PIPAC) interventions performed in 349 patients for peritoneal carcinomatosis treatment: An international survey study

BackgroundPressurized intraperitoneal aerosol chemotherapy (PIPAC) is a new drug delivery method offered in selected patients suffering from non-resectable peritoneal carcinomatosis (PC). As reported experience is still limited, we conducted a survey among active PIPAC centers aiming to report their technical approach and clinical findings. MethodsAn online survey was sent to active PIPAC centers worldwide. The questionnaire consisted of 34 closed questions and was conducted over a period of 3 months beginning in March 2017. ResultsNine out of 15 contacted centers completed the questionnaire totaling 832 PIPAC procedures in 349 patients. Most common indications for PIPAC were PC from gastric, ovarian and colorectal origin. The mean time between each PIPAC procedure was 6–8 weeks. Seven of nine (77.8%) centers evaluate the PCI at every PIPAC procedure. At least four tissue samples for histopathology analysis were retrieved in 5 (55.6%). All centers (100%) use the same chemotherapy protocol: oxaliplatin at a dosage of 92mg/m2 for PC of colorectal origin and a combination of cisplatin and doxorubicin at a dosage of 7.5mg/m2 and 1.5mg/m2, respectively, for other types of PC. Eight centers (88.9%) perform routine radiological evaluation before first PIPAC and after third PIPAC. ConclusionThese data confirm that PIPAC procedures are homogeneously performed in established centers. Standardization of the procedure will facilitate future international multicenter prospective clinical trials.

Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) in Gastric Cancer Patients with Peritoneal Metastasis (PM): Results of a Single-Center Experience and Register Study.

PurposeGastric cancer (GC) patients with peritoneal metastasis (PM) have poor prognosis. Pressurized intraperitoneal aerosol chemotherapy (PIPAC) in combination with systemic chemotherapy is a novel treatment option for patients in stage IV of the disease.Materials and MethodsBetween November 2015 and June 2018, prospective data collection was performed in 24 patients with GC and PM (median age, 57; range, 44–75 years). These patients underwent 46 PIPAC procedures with a median number of 2 interventions per patient (range, 1–6). A laparoscopic access was used and a combined therapy of cisplatin and doxorubicin aerosol was administered.ResultsThe median peritoneal carcinomatosis index before the 1st PIPAC was 14 (range, 2–36), and the median ascites volume in patients before the 1st PIPAC was 100 mL (range, 0–6 mL, 300 mL). Eleven patients, who received 2 or more PIPAC procedures, had decreased and stable volumes of ascites, while only 3 patients displayed increasing volume of ascites. The median overall survival was 121 days (range, 66–625 days) after the 1st PIPAC procedure, while 8 patients who received more than 3 PIPAC procedures had a median survival of 450 days (range, 206–481 days) (P=0.0376).ConclusionsOur data show that PIPAC is safe and well tolerated, and that the production of ascites can be controlled by PIPAC in GC patients. Patients, who received 2 or more PIPAC procedures, reported a stable overall quality of life. Further studies are required to document the significance of PIPAC as a palliative multimodal therapy.Trial RegistrationClinicalTrials.gov Identifier: NCT03100708

Multicentric initial experience with the use of the pressurized intraperitoneal aerosol chemotherapy (PIPAC) in the management of unresectable peritoneal carcinomatosis

BackgroundPIPAC is a recent approach for intraperitoneal chemotherapy with promising results for patients with peritoneal carcinomatosis (PC). We aimed to evaluate the postoperative outcome of PIPAC in patients with non-resectable PC during our initial experience of the technique. MethodsAll patients who underwent PIPAC for non-resectable PC in three centers were analyzed regarding postoperative outcomes. ResultsSeventy-three patients underwent 164 PIPAC. PC was from colorectal, gastric, ovarian, malignant mesothelioma, pseudomyxoma peritonei or other origins in 20, 26, 13, 8, 1 and 5 patients respectively. Forty-five (62%), 31 (42%), 8 (11%), 6 (8%), 1 (1%) patients underwent a second, third, fourth, fifth, and sixth PIPAC respectively. At the time of the first PIPAC, the median PCI was 17 (1–39), 57 patients presented with symptomatic PC (pain: 33; ascites: 35; transit disorder like diarrhea and constipation: 11). PCI improved in 64.5% of patients, 63.5% of patients presented with complete disappearance of symptoms. Major complications occurred as the outcome of 16 PIPAC (9.7%) and 5 (6.8%) patients died within 30 days of the PIPAC procedure. Rate of mortality and major complications 40% and 62% respectively occurred in first 20 treated patients. For 64 (88%) patients, systemic chemotherapy was associated with PIPAC and could be administered after PIPAC with a median delay of 14 days (2–28). ConclusionsImplementing a PIPAC program in association with systemic chemotherapy is feasible and is associated with a risk of postoperative morbidity, even in teams highly experienced in PC management and requires a learning curve in patient selection.

Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) Procedure for Non-resectable Peritoneal Carcinomatosis (with Video)

BackgroundPeritoneal carcinomatosis (PC) is a common evolution of abdominal cancers and is associated with poor prognosis in the absence of aggressive multimodal therapy.1 Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is a safe and innovative approach, which enhances the effect of chemotherapy 2 without reported renal/hepatic toxicity.3,4 It requires mastery of technical aspects to reduce postoperative morbidity, increase effectiveness, and prevent caregiver chemotherapy exposure. We, therefore, report herein the surgical protocol after 2 years of implementation in our university center specialized in PC management, accompanied by a short video, to share our experience. MethodsThe procedure was performed under general anesthesia and capnoperitoneum (12 mmHg, 37 °C) using two balloon trocars placed in the midline, in accordance with the open laparoscopic technique. Explorative laparoscopy allowed Sugarbaker peritoneal cancer index to be determined. Parietal biopsies were taken, and ascites was removed for peritoneal cytology. The nebulizer was inserted and connected to a high-pressure injector. A pressurized aerosol containing chemotherapy agents was then administered; cisplatin (7.5 mg/m2 in 150 ml 0.9%NaCl) immediately followed by doxorubicin (1.5 mg/m2 in 50 ml 0.9%NaCl), or oxaliplatin alone (92 mg/m2 in 150 ml 0.9%NaCl), based on PC origin and chemotherapy history. The aerosol was kept in a steady-state for 30 min then exhausted through a closed filter system, and trocars were retracted. Each step is illustrated in the video. ConclusionThis video protocol provides a better understanding of the PIPAC procedure and the safety measures essential for this method of chemotherapy administration. It should help all teams wishing to implement a PIPAC therapy program.

Peritoneal metastasis from pancreatic cancer treated with pressurized intraperitoneal aerosol chemotherapy (PIPAC).

Patients with peritoneal metastasis (PM) from pancreatic cancer have a short life expectancy. Systemic combination chemotherapy leads to a median overall survival of 7-8 months. Pressurized IntraPeritoneal Aerosol Chemotherapy (PIPAC) is a treatment alternative, where studies in patients with PM from ovarian, gastric and colorectal cancer show a high safety profile and interesting results. This case study report data on the PIPAC treatment in patients with PM from pancreatic cancer. In a standard laparoscopy, chemotherapeutics (cisplatin and doxorubicin) are nebulized within the peritoneal cavity. After 30min, the chemotherapeutics are evacuated through a closed system. The PIPAC procedure is repeated every 4-6 weeks. Five patients with PM from pancreatic cancer were treated with a total of 16 PIPAC procedures. All patients received >1 PIPAC and were eligible for evaluation of histological regression. Four patients demonstrated histological regression, and one patient had stable disease. Three patients are still alive, and the median overall survival is 14 months (range 10-20) since the diagnosis of PM. The histological regression and survival figures in this pilot study suggest activity of PIPAC with low-dose cisplatin and doxorubicin in pretreated peritoneal metastasis of pancreatic origin. This should now be evaluated in prospective studies.

Impact of Pressurized Intraperitoneal Aerosol Chemotherapy on Quality of Life and Symptoms in Patients with Peritoneal Carcinomatosis: A Retrospective Cohort Study.

Background. Peritoneal cancer treatment aims to prolong survival, but preserving Quality of Life (QoL) under treatment is also a priority. Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) is a novel minimally invasive repeatable treatment modality. The aim of the present study was to assess QoL in our cohort of PIPAC patients. Methods. Analysis of all consecutive patients included from the start of PIPAC program (January 2015). QoL (0–100: optimal) and symptoms (no symptom: 0–100) were measured prospectively before and after every PIPAC procedure using EORTC QLQ-C30. Results. Forty-two patients (M : F = 8 : 34, median age 66 (59–73) years) had 91 PIPAC procedures in total (1 : 4x, 17 : 3x, 12 : 2x, and 12 : 1x). Before first PIPAC, baseline QoL was measured as median of 66 ± 2.64. Prominent complaints were fatigue (32 ± 4.3) and digestive symptoms as diarrhea (17 ± 3.75), constipation (17 ± 4.13), and nausea (7 ± 2.54). Overall Quality of Life was 64 ± 3.75 after PIPAC#1 (p = 0.57), 61 ± 4.76 after PIPAC#2 (p = 0.89), and 70 ± 6.67 after PIPAC#3 (p = 0.58). Fatigue symptom score was 44 ± 4.86 after PIPAC#1 and 47 ± 6.69 and 34 ± 7.85 after second and third applications, respectively (p = 0.40). Diarrhea (p = 0.31), constipation (p = 0.76), and nausea (p = 0.66) did not change significantly under PIPAC treatment. Conclusion. PIPAC treatment of peritoneal carcinomatosis had no negative impact on patients' overall QoL and its components or on main symptoms. This study was registered online on Research Registry (UIN: 1608).

Environmental safety during the administration of Pressurized IntraPeritoneal Aerosol Chemotherapy (PIPAC).

Pressurized IntraPeritoneal Aerosol Chemotherapy (PIPAC) is an innovative technique for intraperitoneal drug delivery. This study investigates the efficacy of the occupational health safety measures taken to prevent exposition of healthcare workers to the toxic chemotherapy aerosol. Air samples were taken at the working place of the surgeon and of the anesthetist during 2 PIPAC procedures and analyzed for content of platinum by inductively coupled plasma mass spectrometry (ICP-MS). Airborne particles were quantified in real time. Biological monitoring was performed in two surgeons after 50 PIPAC by examining blood samples for possible traces of platinum. Analysis was performed by an independent company. Safety measures included tightly closed abdomen, operating room (OR), ventilation meeting requirements of ISO norm 14644-1 class 5, closed aerosol waste system and remote control of PIPAC administration. No traces of platinum were found in the air of the OR (detection limit of 0.0001 mg/filter). No specific rise in particle concentration was detected in the air during the PIPAC procedure, patient closure and removal of the sterile drapes. Blood samples of the surgeons showed no traces of platinum. After implementation of adequate safety measures, no signs of environmental contamination or biological exposure of the surgeons were detected during PIPAC.