PIPAC: pressurised intraperitoneal aerosol chemotherapy

PIPAC — pressurised intraperitoneal aerosol chemotherapy — involves administering chemotherapy directly into the abdominal cavity via laparoscopy. It may form part of the treatment for certain tumours of the peritoneum and, in many contexts, is used within specialised programmes or research protocols.

What is PIPAC?

The peritoneum is a thin membrane that lines the inside of the abdomen and covers most of its organs. Some tumours can spread across this surface and form implants in different regions of the abdomen.

During a PIPAC procedure, the anti-tumour drug is converted into fine droplets and delivered into the abdominal cavity via a nebulisation system. The abdomen remains inflated with carbon dioxide, as in other laparoscopic procedures, and the chemotherapy is delivered as an aerosol under controlled pressure conditions.

The combination of direct administration, aerosolisation and pressure is designed to promote contact between the drug and the peritoneal surfaces and its superficial penetration into the tissues. Distribution, however, depends on the abdominal anatomy, the presence of adhesions, the extent of the disease and the technical characteristics of the procedure.

Some of the drug may be absorbed into the systemic circulation. Therefore, although administration takes place within the abdomen, PIPAC should not be regarded as an exclusively local treatment nor as being free from potential systemic effects.

What are the benefits of aerosol and pressurised administration?

PIPAC combines three elements: intraperitoneal administration of the drug, its conversion into an aerosol, and the pressure present within the abdomen during laparoscopy.

The intraperitoneal route places the drug in direct contact with the surfaces affected by the disease. Nebulisation disperses it into small droplets, and the pressure may promote contact and superficial penetration.

This does not mean that the drug is distributed perfectly homogeneously throughout the abdominal cavity, nor that it reaches deep layers of the tumour. Adhesions, anatomy and the distribution of tumour implants can significantly alter how the aerosol reaches each region.

Nor are the drug, the dose and the conditions of administration identical for all tumours. Whilst there is technical consensus, there remain aspects that require further standardisation and long-term evidence.

For which conditions can PIPAC be used?

PIPAC has mainly been studied in people with peritoneal metastases arising from gastric, colorectal and ovarian cancers, as well as other digestive or gynaecological tumours. Its role is not equally well established across all these conditions.

In gastric cancer with peritoneal involvement, some studies have observed favourable changes in biopsy findings and control of certain symptoms, such as ascites, in selected patients. These results must be interpreted within the context of each individual study and do not automatically suggest a survival benefit compared with standard systemic treatment.

In peritoneal metastases from colorectal cancer, the technique has been shown to be suitable for repeated administration in certain patients and to produce local activity. Its role in relation to other oncological strategies continues to depend on the clinical context and the available evidence.

In recurrent or resistant ovarian cancer, histological responses and symptomatic control have also been studied. PIPAC may form part of selected strategies, but does not generally replace established systemic treatments.

In other peritoneal diseases, its use may be limited to specialised programmes or clinical trials. The indication should always be considered within the overall cancer management strategy and not solely on the basis of the presence of disease in the peritoneum.

How is it decided whether PIPAC can form part of the treatment?

The assessment begins by establishing which tumour is causing the peritoneal disease, how it has progressed and what the treatment aims to achieve.

The team analyses the extent and distribution of the implants, any previous treatments received and the possible presence of disease outside the peritoneum. Functional status, nutritional status and renal, hepatic, cardiac, respiratory and haematological function are also assessed.

Another key consideration is whether the abdomen can be accessed via laparoscopy. Previous abdominal surgery may have caused adhesions that make safe access difficult or prevent the creation of an adequate space for aerosol delivery.

The presence of an intestinal obstruction, certain infections, significant clinical deterioration or impaired organ function may alter the indication. The decision must take these factors into account alongside the therapeutic options available for each tumour.

Assessment and planning prior to a session

The assessment usually includes recent imaging scans, blood tests and a review of the pathological diagnosis. Computed tomography (CT) scans enable the extent of the disease to be assessed and determine whether there are any abnormalities outside the peritoneum that might alter the treatment strategy.

Laboratory tests enable us to check kidney and liver function, blood cell counts, coagulation and other relevant parameters before administering the medication and performing the laparoscopy.

Previous abdominal operations and the possibility of adhesions are also carefully reviewed. This information helps to anticipate potential difficulties in accessing the abdominal cavity.

The decision to proceed benefits from a multidisciplinary discussion in which the role of PIPAC is defined in relation to systemic chemotherapy, other cancer treatments and the available alternatives.

How a PIPAC procedure is performed

PIPAC is carried out in the operating theatre under general anaesthesia. The surgeon gains access to the abdomen via small laparoscopic incisions and inserts a camera and the necessary instruments.

Before administering the medication, the peritoneum is examined and the visible distribution of the implants is assessed. Biopsies may be taken from pre-selected areas to ensure comparable samples are available between sessions.

Where ascites is present – that is, a build-up of fluid within the abdomen – some of this fluid may be drained during the procedure to relieve symptoms or for further analysis.

The medication is then delivered via a nebuliser connected to a pressurised delivery system. The chemotherapy remains in aerosolised form within the abdominal cavity for the duration specified by the protocol.

At the end of the procedure, the aerosol is evacuated via a closed, filtered circuit before the instruments are removed. As cytotoxic drugs are used in aerosolised form, the procedure requires specific safety measures designed to control healthcare staff exposure.

Why PIPAC can be administered in several sessions

One characteristic of PIPAC is that it can be repeated. Subsequent sessions allow the drug to be administered again whilst, at the same time, new biopsies can be taken to monitor the progression of the implants.

The number of procedures and the interval between them depend on the tumour, the drug used, the protocol, the patient’s tolerance and the progression of the disease. There is no universal number of sessions applicable to everyone.

Before repeating the treatment, symptoms, laboratory tests, imaging studies and, where available, the histopathological results of previously obtained biopsies are reviewed.

The strategy may be discontinued if the disease progresses, the patient’s general condition worsens, clinically significant toxicity occurs, or it is no longer possible to access the abdomen via laparoscopy with sufficient safety.

Differences between PIPAC, HIPEC and systemic chemotherapy

PIPAC, HIPEC and systemic chemotherapy all use anti-tumour drugs, but the way they are administered, the timing of treatment and their clinical role differ.

PIPAC administers chemotherapy in aerosol form via laparoscopy. It can be carried out over several sessions and does not usually involve extensive surgery to remove all visible implants.

HIPEC — hyperthermic intraperitoneal chemotherapy — uses a heated liquid solution that circulates within the abdomen and is usually administered following cytoreductive surgery aimed at removing visible disease.

Systemic chemotherapy circulates throughout the body and can act on localised disease both inside and outside the abdominal cavity.

Some programmes are investigating strategies that alternate or combine PIPAC and systemic treatment. This approach is tailored to the specific tumour and protocol and does not constitute a universal guideline.

What outcomes can be assessed during treatment

PIPAC allows different aspects of the response to be studied. Biopsies taken during the sessions may reveal changes in tumour tissue and, in certain patients, changes in ascites or certain symptoms may also be observed.

These results need to be interpreted together. A histological response — observed under a microscope — does not necessarily equate to clinical improvement, overall disease control or prolonged survival.

For this reason, assessment is not based solely on biopsies. It also takes into account symptoms, imaging tests, tolerance to treatment, functional status and overall oncological progression.

In some programmes, it has been reported that certain patients were subsequently assessed for cytoreductive surgery. This possibility depends on very specific circumstances and does not constitute a general expectation associated with PIPAC.

Risks and potential complications depending on the treatment and clinical condition

PIPAC combines laparoscopy, general anaesthesia and the intraperitoneal administration of a cytotoxic drug. The type and likelihood of complications depend on the tumour, the patient’s general condition, any previous abdominal surgery, the drug used, and the number and characteristics of the treatment sessions.

Following the procedure, patients may experience abdominal pain, discomfort at the incision sites, nausea, tiredness or a temporary fever. The absorption of some of the chemotherapy drugs may cause renal, haematological, hepatic or metabolic abnormalities, depending on the drug used.

Laparoscopic access may be associated with bleeding, infection or injury to the bowel or other organs, particularly where significant adhesions are present. Thrombotic, respiratory or anaesthesia-related complications may also occur.

On certain occasions, it is not possible to access the abdomen or create a suitable space to administer the aerosol. In this situation, the session may be interrupted before the chemotherapy is administered.

It is not appropriate to summarise the risk using a single figure applicable to all patients. The clinical situation, the tumour, the medication and the technical complexity may vary from one session to another.

Recovery following a PIPAC session

Recovery is usually determined by the laparoscopy, the anaesthesia and the medication administered. As it does not usually involve the extensive resections typical of cytoreductive surgery, the care pathway differs from that of surgery with HIPEC.

In the hours following the procedure, pain, gastrointestinal tolerance, kidney function and other clinical parameters are monitored. Abdominal discomfort, tiredness, nausea, a low-grade fever or certain abnormal laboratory results may persist for some time.

The length of observation or hospital stay depends on the patient’s progress, the protocol and any associated conditions. There is no standard length of hospital stay or recovery period that can be applied across the board.

Before considering a further session, the patient’s recovery and the progression of the disease are assessed.

Alternatives to PIPAC

The alternatives depend primarily on the tumour, the extent of the disease, the treatments already received and the therapeutic objective.

These may include systemic chemotherapy, targeted therapies, immunotherapy, cytoreductive surgery with or without HIPEC, other intraperitoneal treatments or participation in clinical trials.

In certain situations, the strategy may focus primarily on symptom management and maintaining functional status through treatments tailored to each individual’s needs.

The choice of PIPAC is not based on it being a more recent technology than other options. Its potential usefulness depends on there being a reasonable clinical indication and on it fitting appropriately within the overall cancer treatment plan.

Symptoms requiring medical assessment

After discharge, you should contact the healthcare team if you experience a persistent fever, increasing abdominal pain, repeated vomiting, severe bloating, an inability to eat or drink, or significant changes to your wounds.

You should also seek medical assessment if you experience a marked reduction in urine output, bleeding, breathing difficulties, pain or swelling in a leg, or a significant deterioration in your general condition.

Severe pain, loss of consciousness, severe breathing difficulties, significant bleeding or rapid deterioration require urgent medical attention.

Specialists involved

PIPAC requires a specialist assessment of the peritoneal disease, the tumour causing it, and the role this technique may play within the overall cancer treatment programme.

At the Publio Cordón Memorial Hospital, the Peritoneal Carcinomatosis Unit is the unit most directly involved with this procedure. It forms part of the Surgical Oncology Department and is specifically dedicated to the treatment of peritoneal tumour spread. The unit itself lists pressurised intraperitoneal chemotherapy (PIPAC) amongst the areas of expertise of its specialists.

The Oncological Surgery Department is involved in patient selection, performs the laparoscopy, directly assesses the distribution of the disease and carries out the intraperitoneal administration when indicated. The department organises its work into highly specialised units and includes peritoneal carcinomatosis within its approach to complex oncological surgery.

Depending on the tumour of origin, more specialised surgical units may be involved. The Specialised Ovarian Cancer Unit, for example, includes the PIPAC technique within its specialists’ areas of expertise in the context of advanced or relapsed ovarian disease.

Medical Oncology integrates PIPAC into the overall treatment plan and assesses its relationship with systemic chemotherapy, immunotherapy, targeted therapies or other options. Its organisation includes specific units for Gastrointestinal Tumours and Gynaecological Tumours, which are relevant to several of the tumours in which PIPAC has been studied.

Pathology plays a particularly important role in this technique as it analyses the biopsies obtained during the sessions and enables a comparison of histological changes throughout the course of treatment. Diagnostic Imaging is involved in assessing tumour extent and monitoring disease progression.

Anaesthetology and Resuscitation is involved in the preparation and monitoring during each laparoscopy. Hospital Pharmacy is involved in the safe preparation of medication and in procedures relating to the handling of cytostatic drugs, whilst Nursing, Nutrition and other teams may be involved depending on the clinical situation.

Not everyone requires the same combination of specialists at every stage. The treatment pathway is tailored to the primary tumour, the progression of the disease, the number of sessions planned, and any oncological treatments administered concurrently or sequentially.

Preguntas frecuentes

Does PIPAC require the removal of tumour implants?

Answer: Not usually. PIPAC is performed laparoscopically, but its primary aim is not to remove tumour implants extensively. During the procedure, the abdomen is examined, biopsies may be taken, and chemotherapy is administered in the form of a pressurised aerosol. This is a key difference compared with cytoreductive surgery with HIPEC.

Can a session be cancelled before the chemotherapy is administered?

Answer: Yes. At the start of the laparoscopy, the team checks that they can access the abdominal cavity and create sufficient space to administer the aerosol safely. If adhesions or other findings prevent this, the procedure may be halted before the medication is administered.

Are the same medicines always used in PIPAC?

Answer: No. The drug, the dose and the conditions of administration depend on the type of tumour and the protocol used. There are international guidelines aimed at standardising the technique, although differences still persist between indications and treatment programmes.

Why can biopsies be taken during the sessions?

Answer: Biopsies enable peritoneal implants to be examined under a microscope and any changes to be assessed over the course of treatment. This information is interpreted in conjunction with symptoms, imaging tests, patient tolerance and the overall progression of the disease; on its own, it does not determine whether PIPAC should be continued.

Can PIPAC help reduce ascites?

Response: In some patients, a reduction in ascites or an improvement in symptoms associated with peritoneal disease has been observed. The response varies between individuals and tumours, and this effect alone does not allow us to determine the overall course of the disease or survival.

Can PIPAC allow for subsequent cytoreductive surgery?

Answer: In certain programmes, some patients have subsequently been assessed as suitable for cytoreductive surgery following the clinical response observed during treatment. This possibility depends on very specific clinical circumstances and should not be regarded as an expected outcome of PIPAC for all patients.

Is it necessary to remain in hospital after a PIPAC session?

Answer: The length of observation or hospital stay depends on the protocol, recovery following laparoscopy, the medication administered, any associated conditions and the patient’s clinical progress. There is no standard length of hospital stay that can be applied to everyone.

Why does PIPAC require special safety measures in the operating theatre?

Answer: Because a cytotoxic drug is administered in aerosol form during the procedure. The technique uses specific systems and protocols to ensure airtightness, administer the treatment and subsequently remove the aerosol via a filtration system, thereby reducing exposure for healthcare staff.

Medical information for general guidance

This information sheet aims to help you understand what PIPAC is, how aerosol chemotherapy is administered, for which conditions it may be considered, why it may be repeated, and how it fits into a broader cancer treatment programme. It also explains how progress is assessed between sessions, the main risks involved and the available alternatives.

At the Publio Cordón Memorial Hospital, we believe it is important for medical information to be accurate, understandable and useful in guiding each individual throughout their care journey. Our specialists devote part of their work to explaining diseases, tests and treatment options in an accessible way, helping patients and their families to better understand each stage and to participate with greater confidence in decisions regarding their health. This commitment to knowledge and public outreach is also part of our dedication to research and the advancement of medicine.

The information contained in this fact sheet describes the general principles of PIPAC. Its use must be tailored to the individual based on the tumour of origin, the spread and progression of the peritoneal disease, previous treatments, the patient’s general condition, the feasibility of performing laparoscopy and the available alternatives.