PIPAC (Pressurized IntraPeritoneal Aerosol Chemotherapy)
WHAT IS PIPAC:
PIPAC is a novel method of delivering chemotherapy directly into the peritoneal cavity in an aerosol form. It utilizes the physical properties of pressurized gas to distribute the drug evenly and deeply. This allows greater penetration of the drug into the cancer cells, with reduced systemic side effects of the chemotherapy agent. PIPAC is performed as a short and simple laparoscopic (keyhole) surgery. Under general anaesthesia, small instruments will be placed into the abdomen. A micro-pump will deliver the chemotherapy drug into the peritoneal cavity as an aerosol. At the end of the procedure, any residual gas within the peritoneal cavity will be removed.
Currently, PIPAC is a minimally-invasive palliative procedure that aims to prolong survival and preserve quality of life. Due to the low dosage applied, PIPAC can be combined with systemic palliative chemotherapy and has minimal organ toxicity. This procedure can be repeated at intervals of 6 weeks to 3 months.
PERITONEAL CAVITY AND PERITONEAL METASTASIS:
The peritoneum is a membrane that covers the organs in the abdominal cavity. It helps to support these organs and contains the blood vessels and nerves that supply them. The space in the abdominal cavity covered by the peritoneum is also known as the peritoneal cavity.
Metastasis occurs when cancers spread from the initial organ to other parts of the body. Certain cancers, such as those from the stomach colon, and ovary, may metastasize to the peritoneum. Peritoneal metastases denote Stage IV disease in most cancers, and are difficult to treat. These metastases tend to produce fluid in the abdomen, known as ascites or may cause obstruction of the intestines. Peritoneal metastases are difficult to treat, and best managed by a multi-disciplinary team comprising of surgeons and medical oncologists .
More than 10,000 PIPAC procedures have been performed worldwide and the procedure is highly standardized.
The patient is typically admitted for a day surgery procedure. In a negative-pressure operating theatre with laminar air flow, under general anesthesia, a diagnostic laparoscopy will be performed. Following the confirmation and diagnosis of peritoneal carcinomatosis (PC), and suitability of the patient’s abdominal conditions, the aerosolizing device will be set up and the chemotherapeutic agent will be delivered via PIPAC for a total of 30 minutes. After which, the chemotherapy aerosol is removed and the patient will be monitored overnight and discharged the following day.
On 12 December 2016, the first patient in Asia was treated with PIPAC using oxaliplatin by our team at NUHS under the proctorship of Professor Marc Reymond, from the University of Tübingen, Germany, who pioneered this procedure. The patient with pretreated PC of gastric cancer origin, tolerated the procedure well with no toxicity nor adverse events, thus returning to her daily activities almost immediately after the procedure and maintaining a good quality of life. She went on and continued to have her second and third PIPAC procedures done successfully.
With this encouraging initial experience, we collaborated with our medical oncologist Dr Yong Wei Peng to develop a Phase-I dose escalating 3+3 protocol for treating patients with PC of gastrointestinal origin and obtained regulatory approval from the Health Sciences Authority of Singapore and Institutional Review Board (IRB) in 2016.
In addition to the early adoption of PIPAC for the treatment of PC, the multidisciplinary upper gastrointestinal (UGI) cancer group at the National
University Cancer Institute of Singapore (NCIS) is also exploring the efficacy of PIPAC with other potentially suitable chemotherapeutic agents. To that end, we have conducted a preclinical study with paclitaxel, one of the most active anti-cancer agents. Being a large hydrophobic molecule, it is ideal for peritoneal administration as it is only gradually drained from the peritoneal lymphatics and therefore, it can accumulate to high concentrations to act on peritoneal metastases.