DOCTOR Q&A: PRESSURIZED INTRAPERITONEAL AEROSOL CHEMOTHERAPY (PIPAC) FOR ABDOMINAL CANCERS

Pressurized Intraperitoneal Aerosol Chemotherapy is an innovative, minimally invasive approach to delivering chemotherapy directly into the peritoneal cavity, offering new hope for patients with peritoneal carcinomatosis who may not be candidates for complete cytoreductive surgery. This comprehensive Q&A blog explores the fundamentals of PIPAC, including its mechanism, eligibility criteria, procedural steps, advantages, and its role in cancer treatment compared to other therapies, such as HIPEC and systemic chemotherapy. The discussion also addresses common concerns regarding safety, regulatory approval, prognosis, and follow-up care. Providing their expert insights are Dr. Domenico Sabia, Dr. Lana Bijelic, and Dr. Jaume Capdevila, renowned medical and surgical oncologists associated with the Peritoneal Cancer Institute at Teknon Medical Center (Quirónsalud), a premier institution known for its cutting-edge oncological care and commitment to innovative treatments. These leading specialists share their expertise on the latest advancements in PIPAC and its potential to improve outcomes for patients with advanced abdominal cancers.

1. What is PIPAC?

PIPAC (Pressurized Intraperitoneal Aerosol Chemotherapy) is a medical treatment technique designed to deliver chemotherapy directly to the peritoneal cavity (the area that houses the abdominal organs) in a more targeted manner. It involves the use of an aerosol spray to distribute chemotherapy drugs in the peritoneal space under high pressure. This method aims to make chemotherapy more effective for patients with peritoneal carcinomatosis who are initially ineligible for complete cytoreductive surgery. Peritoneal carcinomatosis is the spread of cancer within the peritoneal cavity. Cytoreductive surgery is used to remove as much of a tumor or cancerous tissue in the abdominal cavity as possible. It is often done when the cancer is too widespread to be fully removed, but removing some of it can help improve the efficacy of other treatments, such as chemotherapy, and enhance the patient's overall health and quality of life.

PIPAC allows for a higher concentration of chemotherapy in the abdominal cavity while minimizing systemic side effects.

The procedure is minimally invasive and usually done laparoscopically, meaning through small incisions, with a camera and specialized instruments.

As of 2025, PIPAC has been authorized for use in several regions, including parts of Europe, where it is performed in specialized centers under local medical regulations and ethical guidelines. Countries such as Spain, Germany, France, and Italy have incorporated PIPAC into treatment protocols for peritoneal carcinomatosis.

The specialized technique is yet to receive general regulatory approval in the United States, where it has been the focus of multiple clinical trials approved under the U.S. Food and Drug Administration (FDA) framework.

Regulatory approval for medical treatments varies across countries, with each nation conducting its own evaluations and approval processes based on local healthcare policies and clinical evidence. As a result, the adoption of PIPAC is occurring in phases, with some regions approving its use earlier while others continue to assess its safety and efficacy through clinical trials. While clinical trials in the U.S. contribute to growing research on its potential benefits, the broader clinical adoption of PIPAC will depend on the outcomes of ongoing studies and regulatory evaluations worldwide.

2. Who is a Candidate for PIPAC? What are the Types of Cancer that can be Treated using PIPAC?

Ideal candidates for PIPAC include:

1. Patients with peritoneal carcinomatosis who:
   • Cannot undergo or are not candidates for cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) due to the extent of the disease or other health issues, as stated above. HIPEC involves administering heated chemotherapy drugs directly into the abdomen to eliminate any cancer cells that remain following tumor removal surgery.
   • Have a disease that is refractory or resistant to systemic chemotherapy or where chemotherapy is poorly tolerated.
   • Require palliative care to relieve symptoms like pain, ascites (fluid buildup), or bowel obstruction.
2. Patients with relatively good performance status who can tolerate minimally invasive procedures like laparoscopy.
3. Patients with disseminated abdominal cancers where systemic treatments are less effective or cause intolerable side effects.

Types of cancer that are treatable with PIPAC:

PIPAC has been used successfully to treat a variety of abdominal cancers, especially those with peritoneal spread. Common cancers treated with PIPAC include:

1. Ovarian cancer: Often presents with peritoneal metastasis, and PIPAC can be useful when traditional therapies are not effective.
2. Gastric cancer: Particularly in cases where the cancer has spread within the peritoneum.
3. Colorectal cancer: In advanced stages with peritoneal carcinomatosis, when other treatments are not viable.
4. Appendiceal cancer: This can also cause peritoneal spread, similar to other gastrointestinal cancers.
5. Peritoneal mesothelioma: Though rare, this cancer directly affects the peritoneum and may benefit from PIPAC.
6. Pancreatic or biliary tract cancers that have spread to the peritoneum.
7. Other abdominal advanced cancers

3. Is PIPAC Curative or Palliative?

PIPAC is primarily a palliative treatment, meaning it aims to relieve symptoms, improve quality of life (such as avoiding pain, bowel obstruction, and fluid buildup), and extend survival rather than cure the disease. It is used when peritoneal metastases cannot be surgically removed, and conventional chemotherapy is less effective or not well tolerated to help control disease progression. In some cases, PIPAC can be used as a neo-adjuvant treatment in combination with systemic chemotherapy or surgery to downstage the peritoneal disease and consider the possibility of complete cytoreductive surgery and HIPEC. Neo-adjuvant treatment refers to therapies given before the main treatment, such as surgery, to shrink or reduce the spread of the cancer. This initial treatment aims to make the subsequent primary treatment - such as complete cytoreductive surgery and HIPEC - more effective.

4. Is PIPAC Only Used When Cytoreductive Surgery and HIPEC Are Not Possible?

PIPAC is often used when CRS and HIPEC are not feasible, but it is not exclusively limited to this scenario.

Cytoreductive surgery and HIPEC are considered more aggressive, curative-intended treatments for peritoneal carcinomatosis, where the visible tumor is surgically removed (CRS), followed by the direct infusion of heated chemotherapy (HIPEC) into the

peritoneal cavity. These procedures are the gold standard treatment for patients with limited peritoneal spread.

However, PIPAC is a less invasive option, which can be utilized in situations where:

1. CRS/HIPEC is not possible due to the extent of the disease, poor performance status, or other medical conditions that preclude surgery.
2. CRS/HIPEC has failed, or the patient is not a candidate for repeated surgery.

5. What Preparations are Needed Before Undergoing PIPAC?

Before undergoing PIPAC, certain preparations are necessary to make sure the procedure is as safe and effective as possible. These preparations are typically done in consultation with the surgical and oncological teams.

Pre-procedure Assessments

• Medical evaluation: A thorough medical assessment is performed to evaluate the patient's overall health and suitability for the procedure. This includes checking vital signs, laboratory tests, and assessing organ function (e.g., liver, kidney, heart).
• Imaging: Imaging studies like CT scans or MRIs of the abdomen are typically performed to assess the extent of peritoneal carcinomatosis and determine if PIPAC is appropriate for the patient.
• Blood tests: Standard blood tests (e.g., CBC, liver and kidney function, coagulation profile) are conducted to ensure that the patient is fit for surgery and anesthesia.
• Performance status assessment: An evaluation of the patient's performance status (general health and ability to carry out daily activities) is crucial, as PIPAC is generally recommended for patients who are not in a very debilitated state.

Pre-operative Instructions

• Fasting: The patient will likely be instructed to fast for a certain number of hours before the procedure (usually 6 hours) to reduce the risk of aspiration during anesthesia.
• Medication adjustments: The patient may be required to adjust or temporarily stop certain medications, particularly blood thinners or medications that impact the immune system, to reduce the risk of complications. This should be discussed with the medical team.
• Prophylactic antibiotics: To mitigate the risk of infection, antibiotics may be given prior to the procedure, especially since PIPAC involves laparoscopic surgery.
• Stop chemotherapy: the patient will be required to stop chemotherapy approximately 2 weeks before the procedure.

Laparoscopy and Anesthesia Preparation

• Laparoscopic procedure setup: Since PIPAC is typically performed using a minimally invasive laparoscopic technique, preparation involves ensuring that the patient is properly positioned for the procedure and that necessary equipment is ready.
• General anesthesia: PIPAC is usually performed under general anesthesia, and hence, an anesthesiology assessment will be done to ensure the patient can safely undergo the procedure.
• Intravenous access: A line will be placed to administer fluids, medications, and anesthesia during the procedure.

Patient Education

• Informed consent: Patients are thoroughly educated about the procedure, potential benefits and risks, and any available alternative. It is mandatory to have patient consent before carrying out the procedure.
• Discussion of goals: Since PIPAC is a palliative treatment, it is important for patients to understand that the goal is symptom management and disease control rather than a cure. The oncological team will discuss expectations and the potential outcomes of the treatment.

Other considerations

• Psychological support: Some patients may experience emotional distress due to the nature of their cancer and the treatment. Psychological support or counseling may be helpful in preparing them mentally for the procedure and the challenges ahead.
• Post-procedure care planning: The medical team will also plan for post-operative care, which may include pain management, monitoring for complications, recommendations, and further treatments if necessary.

6. How is PIPAC Performed?

Pressurized Intraperitoneal Aerosol Chemotherapy is a minimally invasive procedure that delivers chemotherapy directly into the peritoneal cavity using a pressurized aerosol. The procedure is typically performed laparoscopically, meaning through small incisions in the abdomen with the aid of a camera. The surgeon usually makes two small incisions (ports) in the abdomen to insert the laparoscope (a thin tube with a camera inside its tip) and other surgical instruments. The surgical team then pumps carbon dioxide gas into the abdominal cavity to create space for better visibility and access to the peritoneum.

Inspection and Evaluation

• After the incisions are made, the surgeon uses the laparoscope to carefully examine the peritoneal cavity and assess the extent of the cancer (Peritoneal Cancer Index - PCI). The Peritoneal Cancer Index (PCI) is a scoring system used by doctors to assess the spread and severity of cancer within the peritoneal cavity. It helps evaluate how much cancer has spread and can guide treatment-related decisions, such as the choice of therapies like PIPAC or the need for surgery.
• The surgeon may aspirate ascitic fluid if present and take biopsies (tissue samples for further examination) of peritoneal metastases.

Administration of Chemotherapy

• A specialized pressurized aerosol device is used to deliver the chemotherapy drugs directly into the peritoneal cavity.
• The chemotherapy is sprayed as an aerosol mist under high pressure, allowing it to reach the entire peritoneal surface and penetrate the tumors more effectively.
• This technique allows for better distribution of the chemotherapy into the abdomen space, reaching areas that are hard to treat with traditional intravenous chemotherapy.

Duration and Monitoring

• The administration of the aerosolized chemotherapy might take from 6 to 30 minutes.
• During the procedure, the surgeon continuously monitors the patient’s vital signs and the flow of the aerosol to ensure safe and effective delivery.

Completion of the Procedure

• After the chemotherapy is administered, the pressurized gas is removed, and the laparoscopic instruments are carefully withdrawn.
• The small incisions are closed, typically with absorbable stitches or small staples.
• Patients are observed for any immediate post-operative complications.

Post-operative Care

• Patients are typically monitored for 2-3 hours in a recovery room following the procedure as the anesthesia wears off.
• Post-operative pain is addressed as needed, typically requiring a 1-2 day hospital stay for observation.
• PIPAC typically involves a shorter recovery period compared to traditional surgery since it is a minimally invasive procedure.

7. How Long is the PIPAC Procedure? Is PIPAC an Outpatient Procedure?

Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) typically takes about 90 to 120 minutes to complete. However, the entire process, including preparation, anesthesia, and recovery, may take several hours.

PIPAC is generally not an outpatient procedure. It is usually performed in a hospital setting because it requires general anesthesia, and patients typically need to be monitored post-procedure for any immediate side effects or complications. Most patients stay in the hospital for at least one night, but the duration may vary based on individual recovery and the hospital’s protocol.

8. What Does Follow-up Care Look Like After PIPAC?

Comprehensive follow-up care is crucial after PIPAC to ensure proper recovery, assess treatment response, and manage any adverse effects. Here's what follow-up care typically involves:

1. Scheduled Follow-Up Visits:
   1. Patients are scheduled for follow-up appointments with their oncologist or surgical team (in person or virtually), usually within a few weeks after the procedure. These visits help assess recovery, discuss any side effects, and plan further treatment.
   2. Imaging studies (e.g., CT or MRI scans) and blood tests may be conducted to evaluate the response to the treatment.
2. Monitoring Side Effects:
   1. Common side effects of PIPAC, such as abdominal pain, nausea, or fatigue, are monitored. Physicians may prescribe medications to manage these symptoms.
   2. Any signs of complications, like infection or bowel obstruction, are addressed promptly.
3. Treatment Planning:
   1. PIPAC is repeated every 2 cycles of intravenous chemotherapy and at least 3 times to assess its effect.
   2. The healthcare team will evaluate whether further cycles of PIPAC, additional chemotherapy, or other treatments are needed based on the patient's condition and disease progression.
4. Supportive Care:
   1. Nutritional support, pain management, and psychological support may be part of the follow-up care to ensure overall well-being.
   2. Patients may be referred to support groups or counseling services to help cope with the emotional and psychological aspects of cancer treatment.
5. Long-Term Monitoring:
   1. Long-term follow-up involves regular check-ups to monitor for recurrence, progression of the disease, or the possibility of performing radical surgery.
   2. Oncologists will tailor the frequency and type of follow-up based on the individual patient's response and overall health.

Follow-up care is personalized and focuses on the specific needs of each patient, aiming to ensure the best possible outcomes.

9. What are the Differences Between HIPEC, PIPAC, and Traditional Systemic Chemotherapy?

HIPEC and PIPAC are both innovative treatments for cancers that have metastasized (spread) to the peritoneal cavity. They differ significantly from each other and from traditional systemic chemotherapy in their delivery method, application, and overall approach to treating cancer.

Key Differences:

• Targeting: HIPEC and PIPAC deliver chemotherapy directly to the peritoneal cavity, targeting cancer cells more precisely, whereas systemic chemotherapy treats the whole body.
• Invasiveness: HIPEC is associated with a major surgical procedure (CRS), while PIPAC can be performed as a standalone procedure and is minimally invasive.
• Side Effects: HIPEC and PIPAC have more localized side effects, whereas systemic chemotherapy can have widespread side effects due to its impact on the entire body.

10. What are the Advantages of PIPAC?

Pressurized Intraperitoneal Aerosol Chemotherapy offers several advantages, particularly for patients with peritoneal carcinomatosis or advanced peritoneal cancers. These advantages include:

1. Minimally Invasive Procedure:

• Laparoscopic Approach: PIPAC is performed using minimally invasive laparoscopic surgery, which involves small incisions. Patients undergoing this procedure may experience a quicker recovery, reduced post-operative discomfort, and a lower incidence of complications than those undergoing open surgery.
• Repeatability: PIPAC can be safely repeated multiple times (typically every 5-8 weeks), allowing for ongoing treatment cycles without the need for major surgery each time.

2. Localized Drug Delivery:

• Targeted Therapy: PIPAC delivers chemotherapy directly to the peritoneal cavity, where the cancer cells are located, ensuring higher drug concentration at the tumor site and minimizing systemic exposure.
• Reduced Systemic Toxicity: Since the chemotherapy is contained within the peritoneal cavity, the systemic absorption is lower, leading to fewer side effects compared to traditional systemic chemotherapy.

3. Enhanced Drug Penetration:

• Pressurized Aerosol: The use of pressurized aerosol enhances the penetration of chemotherapy drugs into the peritoneal surface and tumor nodules. This pressurization improves the distribution of the drug, ensuring more uniform contact with the affected tissues.

4. Effective for Advanced or Recurrent Disease:

• Palliative Care: PIPAC can be an option for patients with advanced, inoperable, or recurrent peritoneal cancers, offering a palliative benefit by slowing disease progression and reducing symptoms and, in some cases, to reconsider the option of radical oncologic surgery associated with HIPEC.
• Quality of Life: By controlling ascites, pain, and other symptoms, PIPAC can improve the quality of life for patients who may have limited options.

5. Combination with Other Therapies:

• Adjunctive Treatment: PIPAC is almost always associated with systemic chemotherapy or other treatments, offering a multi-modality approach to cancer management. This combination can enhance overall treatment efficacy.

6. Lower Drug Doses:

• Reduced Chemotherapy Dose: PIPAC requires lower doses of chemotherapy drugs compared to systemic treatments, which contributes to its lower side effect profile while maintaining therapeutic efficacy.

7. Real-Time Assessment:

• Diagnostic Value: During PIPAC procedures, the surgeon can directly visualize the peritoneal cavity and assess the extent of the disease with more precision compared to conventional imaging tests (CT, MRI PET-CT) that have some limitations, especially when the tumor is small, which occurs most of the time.
• Biopsies can be taken to monitor disease progression or response to treatment.

11. What are the Contraindications for PIPAC?

PIPAC is a specialized treatment, and certain contraindications must be considered to ensure patient safety. The contraindications for PIPAC can be categorized into absolute and relative contraindications:

Absolute Contraindications:

1. Extensive Abdominal Adhesions:

• Severe adhesions in the abdominal cavity can prevent the even distribution of the aerosolized chemotherapy and hinder the effectiveness of the procedure.

2. Uncontrolled Infection:

• Active infections, particularly in the peritoneal cavity or abdominal area, pose a significant risk for complications during and after the procedure.

3. Bowel Obstruction:

• Complete bowel obstruction can complicate the procedure and increase the risk of perforation or other severe complications.

4. Severe Cardiopulmonary Conditions:

• Patients with significant heart or lung disease may not tolerate the insufflation (introduction of gas) required during the laparoscopic procedure, as it increases intra-abdominal pressure and affects cardiovascular and respiratory function.

5. End-Stage Disease or Poor Performance Status:

• Patients with poor health status or those who are in the terminal stages of cancer may not be suitable candidates due to the potential risks outweighing the benefits of the procedure.

Relative Contraindications:

1. Moderate Adhesions:

• While some adhesions may be manageable, moderate adhesions could complicate the delivery of the aerosol. Each case requires careful evaluation.

2. Substantial Tumor Burden:

• A very large tumor load in the peritoneal cavity might limit the effectiveness of PIPAC. In such cases, the treatment might be less beneficial.

3. Severe Malnutrition or Cachexia:

• Patients with extreme weight loss or poor nutritional status may face higher risks during surgery and slower recovery. Nutritional optimization might be needed before considering PIPAC.

4. Previous Abdominal Surgeries:

• Extensive previous surgeries can increase the risk of complications due to scar tissue or altered anatomy. A thorough assessment is required to determine feasibility.

12. What is the Prognosis and Success Rate of PIPAC?

The prognosis and success rate of Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) can vary widely depending on several factors, including the type of cancer, histology, stage of the disease, previous treatments, and the patient's overall health. However, PIPAC has shown promising results, particularly in improving quality of life, with palliative benefit in patients with advanced peritoneal carcinomatosis, and in some cases, offering the possibility of re-evaluating a radical oncological surgical treatment.

1. Type of Cancer:

• PIPAC is most commonly used for peritoneal metastases from cancers, such as gynecologic, colorectal, gastric, bilio-pancreatic, and mesothelioma. The prognosis tends to be better in cancers that are more chemosensitive than in those that are less responsive to systemic treatments. When cancer cells are chemosensitive, they are more likely to shrink or slow their growth when treated with chemotherapy drugs, leading to a potentially better prognosis.

2. Stage of Disease:

• PIPAC is often used in advanced or recurrent cases where the disease has spread extensively within the peritoneal cavity. In such cases, the primary goal may be to control symptoms and slow disease progression rather than cure.

3. Previous Treatments:

• Patients who have undergone multiple lines of systemic chemotherapy may have a different prognosis compared to those receiving PIPAC as a relatively early intervention.

4. Overall Health:

• The patient's performance status, nutritional status, and presence of comorbidities can significantly influence the outcome and tolerance to PIPAC.

Success Rates:

1. Response Rates:

• Studies have shown partial response or disease stabilization in many patients treated with PIPAC. For example, in cancers such as ovarian and colorectal, treatments are able to control the disease in about 50% to 60% of cases. This means that in these cases, the cancer either shrinks (partial response) or stops growing (stable disease).

2. Symptom Control:

• PIPAC is particularly effective in alleviating symptoms such as fluid accumulation and abdominal pain, improving patients' quality of life even if the overall survival benefit may be limited in some cases.

3. Survival Benefit:

• Survival outcomes following PIPAC can vary depending on the cancer type. Studies have shown that median survival times for patients with advanced ovarian cancer can range from 10 to 24 months. In contrast, median survival in colorectal cancer may be approximately 12 to 16 months, with significant variability influenced by factors such as tumor burden and prior treatment responses. Median survival time is a way to describe how long patients typically live after their diagnosis. It means that half of the patients live longer than this time, and the other half live for a shorter period.

Ongoing Research:

PIPAC is still considered a relatively new technique, and ongoing clinical trials aim to better define its role in cancer treatment, optimal patient selection, and combination with other therapies. These studies are expected to further clarify long-term outcomes and improve treatment protocols.

13. What are the Side Effects and Complications of PIPAC?

Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) is generally well-tolerated and associated with fewer systemic side effects compared to traditional intravenous (IV) chemotherapy, but it can still lead to specific side effects and complications. Here's a detailed comparison:

Side Effects of PIPAC:

1. Local Abdominal Discomfort:

• Mild to moderate abdominal discomfort is a common side effect after the procedure. This can be attributed to the introduction of gas (usually carbon dioxide) into the abdomen and the effects of chemotherapy on the peritoneal lining.

2. Nausea and Vomiting:

• These are less common and usually less severe than with systemic chemotherapy but can still occur.

3. Fatigue:

• Similar to other cancer treatments, fatigue is a common side effect, though typically less intense than with systemic chemotherapy.

4. Inflammation:

• Inflammation of the peritoneum (peritonitis) can occur, though it is usually mild and self-limiting.

5. Delayed Bowel Function:

• Some patients may experience a temporary slowing of bowel movements or mild ileus after the procedure.

6. Anesthesia-related Side Effects:

• As PIPAC is performed under general anesthesia, side effects such as drowsiness, nausea, or rare complications related to anesthesia may occur.

Complications of PIPAC:

1. Infection:

• While uncommon, infections, such as those at the port site or within the peritoneal cavity (peritonitis), can occur.

2. Adhesion Formation:

• PIPAC may cause or worsen adhesions in the abdominal cavity, which can lead to complications in future surgeries or bowel obstruction. Adhesions are bands of scar tissue that can form after surgery or inflammation, causing organs and tissues to stick together.

3. Bowel Perforation:

• A rare but serious complication where the bowel is accidentally perforated during the procedure.

4. Hematoma or Bleeding:

• Minor bleeding, especially at the port sites, may occur.

5. Hernia:

• A hernia can appear at the port site, after some sessions.

Early clinical results for PIPAC have shown encouraging outcomes for patients with peritoneal malignancies originating from various sources, including mesothelioma, stomach, ovaries, colon, pancreas, and the hepatobiliary system. PIPAC may provide significant benefits for patients with limited treatment options, offering the potential for improved disease control and potentially prolonging survival as well.

 

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