Peritoneal carcinomatosis (PC) is a route of metastasis for many tumors with limited treatments and is considered dissemination localized into the peritoneal cavity. Pressurized intraperitoneal aerosol chemotherapy (PIPAC) allows intraabdominal delivery of chemotherapy by laparoscopy¹. One of the principles is to increase the tissue penetration of chemotherapeutic agents by hyperpressure. The concentration of the drugs used is lower than for intravenous infusion and should therefore reduce systemic side effects.

The selection of patients for PIPAC is based on the presence of unresectable PC, type of tumor, the extent of the disease and the patient’s general health status². PIPAC can be offered to patients in which the disease is stabilized by systemic chemotherapy, but is unresectable because of too extensive involvement (impossible to achieve complete cytoreduction, [PCI > 20] and not eligible for hyperthermic intraperitoneal chemotherapy [HIPEC]) or for those wishing to stop intravenous chemotherapy; it can be offered to patients who have resistance to systemic intravenous chemotherapy or in the first line to reinforce intravenous chemotherapy in order to make resectable an extensive peritoneal disease³. Several studies have demonstrated a benefit in the use of PIPAC as an alternative to HIPEC in the treatment of PC in different types of tumor⁴.

PIPAC is performed through standard laparoscopy under general anesthesia⁵. After the administration of antibiotic prophylaxis with cefuroxime 3 g and metronidazole 1.5 g, the laparoscopy is performed using either an open technique, the Veress needle or ultrasound guidance if there is suspicion of parietal adhesions. Pneumoperitoneum is set with normothermic CO₂ insufflation at a pressure of 12 mm Hg. Balloon fixation trocars are used to avoid the risk of unexpected cannula migration with gas or chemotherapeutic agent leak during the procedure. Two working trocars of 5 mm (lateral) and 12 mm (infraumbilical midline) size are used. A 30° laparoscope provides adequate visualization. The quantification of PC is initially performed based on the distribution and size of the lesions by mapping of the peritoneum according to Sugarbaker’s peritoneal cancer index (PCI) ⁶. Ascites is evacuated and the abdominal cavity is flushed with 500 mL saline at 37 °C. Four biopsies are obtained from the peritoneal metastases for histological confirmation of disease progression or response. During surgery, the differentiation between metastases and fibrotic nodules is not simple. Ideally, biopsies should be obtained from the four abdominal quadrants. The biopsy sites can be marked by clips and a 2 × 2 cm² localized peritonectomy seems to increase the effectiveness of the histological diagnosis.

Once the disease extent has been evaluated, the PIPAC procedure starts. Capnopen® (Capnomed, Villingendorf am Rhodweil, Germany), is a a 9-mm device with a high-pressure nebulizer connected to a high-pressure injector. This nebulizer generates an aerosol sphere of chemotherapeutic agents that is homogeneously distributed in the peritoneal cavity and is inserted through a balloon trocar with a diameter of 12 mm (Figures 1 and 2).

Figure 1 Capnopen device. The Capnopen device is a concentric probe that encloses a central valve. The chemotherapy solution is transported from the injector to the device via a high-pressure infusion line with an axial spiral lumen and is aerosolized by a rotating needle with a manometric fulcrum. It also has a valve mechanism that prevents chemotherapy solution from backing into the infusion line. The eccentric pressure produces micro-particles that will ultimately aerosolize chemotherapy from the tip of the Capnopen into the patient’s abdomen. 

Figure 2 Diagram of the administration of pressurized intraperitoneal aerosol chemotherapy (PIPAC). The chemotherapeutic agent is administered by a remote-controlled high-pressure injector connected via a high-pressure infusion line to the Capnopen device inserted into the abdomen through a balloon fixation trocar. The administration is monitored in real time with laparoscopic visualization. The aerosol is distributed through the entire abdomen thanks to the size of the pressurized particles. 

It is essential to prevent chemotherapeutic agent leaks to avoid accidental exposure of the patient or surgical team. Maintenance of a leak-free pneumoperitoneum through the trocars is mandatory. The tightness of the abdomen should be documented via a zero flow of CO₂. Chemotherapy administration is made by remote control, since all the staff must leave the operating room during drug administration. Nebulization is controlled through the laparoscope held by an instrumental arm. The environmental risk of chemotherapy exposure can be measured through analysis of the air in the operating room or by taking blood samples of the PIPAC staff in order to detect platinum concentrations. Reymond et al. recommend placing a closed line system with two micro-particle filters in series connected to the trocar through which the pneumoperitoneum will be evacuated. The use or laminar air flow is recommended during the procedure or a plastic curtain can be hanged over the patient and connected to the aspiration system with two serial particle filters to avoid concentration of chemotherapy drugs in the air^4,7,8.

After checking the safety procedures, aerosolization of chemotherapy drugs is initiated. This stage lasts about 5 to 8 minutes, depending on the dose used. For patients with PC due to colorectal cancer, oxaliplatin 92 mg/m² in 150 mL 5% dextrose solution is recommended. For other cancers, the indication is a combination of cisplatin 7.5 mg/m² in 150 mL normal saline and doxorubicin 1.5 mg/m² in 50 mL normal saline⁴. The flow rate should be of 30 mL/ min at a maximum pressure of 200 psi (13.8 bar) at a temperature of 37 °C. The chemotherapy is then left the abdomen for 25 minutes for simple diffusion.

Then, the pneumoperitoneum is evacuated through two sequential micro particle filters connected to the gas evacuation and ventilation system of the operating room. The trocars are removed, and the wall is closed with standard sutures. At the end of the procedure, it is important to follow the regulations for handling and disposal of the material used, including the trocars, fields, lines and solutions.

If the postoperative period is uneventful, the patients can be discharged at the day of procedure or the first postoperative day. Blood samples are obtained on day 1 and 10 after each PIPAC treatment to document toxicity. Screening for adverse events is recommended according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 (National Cancer Institute) within 30 days from the procedure⁴. The biopsies and cytology samples should be reported by using the peritoneal regression grading score (PRGS). Baseline values correspond to the first PIPAC procedure for future comparisons⁹ (Table 1). Quality of life is monitored by the EORTC-QLQC30 questionnaire at baseline, day 60, day 120 and day 180 after the procedure¹⁰. Some ethical and technical considerations are essential for the safe management of chemotherapeutic agents. Surgeons require a certification to perform the PIPAC technique. This certification is obtained after completing a theoretical and practical training course under the supervision of the International Society of Pleura and Peritoneum. This certification ensures the implementation of PIPAC protocols according to international standards and minimizes the possibility of complications related to the technique. The distribution of Capnopen has been authorized in Argentina by the ANMAT (Administración Nacional de Medicamentos, Alimentos y Tecnología Médica) since June 2019.

Our experience includes 12 patients treated with the PIPAC technique due to colorectal cancer, gastric cancer and gynecologic cancer.