HIPEC: hyperthermic intraperitoneal chemotherapy

HIPEC — hyperthermic intraperitoneal chemotherapy — involves administering heated chemotherapy into the abdominal cavity during a surgical procedure. It is usually carried out following cytoreductive surgery, and its indication depends on the type of tumour, the extent of the disease and the feasibility of adequately removing visible implants.

What is HIPEC?

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

When treatment includes cytoreductive surgery, the primary aim is to remove any visible disease that can be safely and clinically appropriately excised. Once this phase is complete, and where clinically indicated, a chemotherapy solution heated to a controlled temperature is circulated through the abdominal cavity.

Direct administration allows the drug to come into contact with the peritoneal surfaces and achieve high concentrations in the treated area. Heat can increase the activity of certain drugs and promote their penetration into the surface tissues.

Some of the chemotherapy may be absorbed into the systemic circulation. For this reason, HIPEC should not be regarded as an exclusively local treatment or as a form of chemotherapy free from systemic effects.

Why HIPEC is combined with cytoreductive surgery

The penetration of chemotherapy administered via HIPEC is limited and does not allow tumour masses of significant size to be treated on its own. For this reason, the possibility of removing visible disease beforehand is of central importance in determining the indication.

Cytoreductive surgery and HIPEC fulfil different roles within the same treatment strategy. The former targets macroscopic disease; the perfusion subsequently aims to target any microscopic tumour cells that may remain on the abdominal surfaces.

The clinical outcomes observed usually relate to the treatment as a whole, which may also include systemic chemotherapy or other therapies. This means that not all the benefit derived from the combined strategy can always be attributed to HIPEC alone.

For which tumours can HIPEC be used?

The indication varies significantly depending on the tumour of origin. International guidelines are not identical for all peritoneal diseases, and the scientific evidence supporting perfusion therapy differs in each context.

In peritoneal pseudomixoma, which is frequently associated with certain mucinous tumours of the appendix, cytoreductive surgery with HIPEC is a widely accepted strategy when the disease is resectable and the patient’s clinical condition allows for a procedure of this magnitude.

In malignant peritoneal mesothelioma, this combination may offer the prospect of long-term control in carefully selected patients. Given the complexity of the treatment, the indication benefits particularly from assessment at centres with specific expertise.

In peritoneal metastases from colorectal cancer, cytoreductive surgery may benefit certain patients. The additional benefit of HIPEC depends largely on the protocol, the drug used and the characteristics of the disease; consequently, it is not routinely applied in all cases.

In ovarian cancer, HIPEC may form part of specific treatment strategies, particularly in certain scenarios involving interval surgery following prior systemic treatment. Its use is not extended to all patients with advanced or recurrent disease.

In other peritoneal tumours, the technique may be reserved for very specific indications, specialised protocols or clinical trials.

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

The presence of tumour disease in the peritoneum does not, in itself, determine whether HIPEC is indicated. The decision begins with an assessment of which tumour is causing the disease, how the implants are distributed, and whether a sufficiently adequate cytoreduction can be achieved.

The team analyses the tumour’s biology, the extent and distribution of the disease, the involvement of the small intestine and other vital structures, the presence of metastases outside the abdomen, and the response to previous treatments.

General health, renal, cardiac and respiratory function, nutritional status and the patient’s capacity for recovery are also assessed. The potential benefit of the perfusion must be weighed against the fact that the associated surgery may be extensive and physiologically demanding.

The decision is made on a case-by-case basis and must take into account both the available evidence for that particular tumour and the specific characteristics of the disease and the individual.

Pre-treatment assessment and planning

The assessment usually includes a CT scan and, where it provides additional information, an MRI, PET scan or other imaging tests. These investigations enable the extent of the disease to be estimated and an assessment to be made of which structures may be affected.

Pathological examination confirms the origin and characteristics of the tumour. In certain cases, a diagnostic laparoscopy may be performed to directly examine the abdomen, obtain samples and assess the possibility of achieving adequate cytoreduction.

The peritoneal carcinomatosis index can be used to describe the extent and size of implants in different regions of the abdomen. Its interpretation depends on the tumour and does not, on its own, determine whether the treatment strategy is appropriate.

Laboratory tests enable the assessment of renal and hepatic function, blood cells, coagulation and other parameters necessary for planning complex surgery and the administration of chemotherapy. Nutritional status also warrants specific assessment as it may influence recovery.

Planning is completed with an anaesthetic assessment and, where necessary, with measures aimed at improving functional reserve prior to the procedure.

How HIPEC is administered

The treatment is carried out under general anaesthesia as part of a surgical procedure that may last several hours. Before starting the perfusion, the team examines the abdomen and performs the necessary cytoreductive surgery to remove any visible tumour implants.

Once this phase is complete, tubes are inserted and connected to a system that heats and circulates the chemotherapy solution through the abdominal cavity. The fluid flows in and out in a controlled manner whilst the temperature and parameters specified by the protocol in use are maintained.

The drug, concentration, temperature and duration of the infusion depend on the tumour and the centre’s strategy. There is no single HIPEC regimen that is suitable for all peritoneal diseases.

Once finished, the solution is drained and the abdomen is examined before completing the reconstructions and surgical closure.

Open and closed HIPEC

The perfusion can be administered with the abdomen temporarily open or closed. These modalities describe two technical methods of delivering chemotherapy, not two different cancer treatments.

In the open technique, also known as the ‘colosseum’ technique, the abdomen is kept temporarily open using a containment system, allowing the team to directly visualise and manipulate the structures during perfusion.

In the closed technique, the tubes are positioned and the abdomen is temporarily closed whilst the solution circulates inside it. This system helps maintain temperature and reduces environmental exposure to the drug.

The choice depends on the protocol, the drug used, the surgery performed and the team’s experience. There is no universally demonstrated oncological superiority of one approach over the other.

What happens if the plan needs to be changed during surgery

Tests carried out before surgery help to estimate the distribution of the implants, but they do not always accurately reveal the full extent of the disease. Some findings can only be fully assessed during the surgical exploration.

If the disease is found to be more extensive than anticipated, or if its distribution necessitates resections involving disproportionate risk or functional loss, the team may modify the initial plan.

In such circumstances, a decision may be taken to limit or discontinue cytoreductive surgery and not to administer HIPEC if the conditions justifying its use are no longer met.

This decision forms part of the safety planning for complex oncological surgery. It allows the treatment to be adapted to the actual situation encountered and helps to avoid procedures whose consequences may outweigh the expected benefit.

Benefits and objectives of treatment

In certain peritoneal cancers and in carefully selected patients, the strategy combining cytoreductive surgery and HIPEC can offer prolonged periods of disease control and, in some contexts, may be considered with curative intent.

The likelihood of benefit depends on the primary tumour, its biological behaviour, the extent of the disease, the degree of cytoreduction achieved, and the overall cancer treatment regimen used.

In some peritoneal pseudomixomas and certain resectable peritoneal mesotheliomas, the strategy may be considered with the aim of cure. This means that the aim is to remove all detectable disease and achieve prolonged control; however, it does not guarantee that the tumour will not recur.

In colorectal and ovarian cancer, the specific contribution of HIPEC is more variable. For this reason, the potential benefits must be explained in the context of the specific clinical scenario and should not be automatically attributed to the perfusion itself.

Risks and potential complications depending on the surgery and treatment administered

HIPEC is usually part of a highly complex oncological procedure. The type and likelihood of complications depend mainly on the extent of the cytoreductive surgery, the organs treated, the medication used and the clinical characteristics of each individual.

Surgery may be associated with bleeding, infection, thrombosis, respiratory complications, impaired wound healing and delayed bowel recovery. When gastrointestinal resections are performed, anastomotic leaks, fistulas, obstruction or the need for additional procedures may occur.

Chemotherapy administered during HIPEC may contribute to renal, haematological, hepatic or metabolic abnormalities, depending on the drug used and the amount absorbed.

When surgery requires extensive bowel resections, a temporary or permanent stoma may be necessary. This possibility is related to the cytoreductive surgery performed and not to the perfusion alone.

The risk cannot be expressed as a single figure applicable to everyone. A limited procedure and extensive multi-organ surgery represent very different situations and must be assessed on a case-by-case basis.

Recovery following HIPEC surgery

Recovery depends largely on the surgery performed prior to the infusion. During the first few days, pain, breathing, kidney function, fluid balance, blood parameters and the return of bowel function are monitored.

Food is reintroduced gradually. In certain situations, it may be necessary to use intravenous or tube feeding for a period of time, and where a stoma has been created, the nursing team provides training on how to care for it.

After discharge, patients may continue to experience tiredness, loss of strength, reduced appetite and changes in bowel habits. Recovery can take weeks or months and may require nutritional support, adapted exercise and rehabilitation.

Follow-up care depends on the tumour, the pathological findings, the extent of the surgery and any previous treatments administered. Medical Oncology takes all this information into account when deciding on the next stages of treatment.

Alternatives to HIPEC

The alternatives depend on the tumour, the extent of the disease and the treatment objective. They may include systemic chemotherapy, cytoreductive surgery without HIPEC, targeted therapies, immunotherapy, other intraperitoneal treatments or participation in clinical trials.

In some cases, the aim may be to control the progression of the disease or relieve symptoms using less invasive strategies, tailored to the patient’s general condition and clinical priorities.

HIPEC is not, by definition, a superior option. Its value depends on there being a specific indication and on it being reasonably integrated into the overall cancer management strategy.

Symptoms requiring medical assessment

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

You should also seek medical assessment if you experience a marked reduction in urine output, breathing difficulties, swelling or pain in a leg, or significant changes in the functioning of an ostomy.

Severe pain, significant bleeding, loss of consciousness, severe breathing difficulties or a rapid deterioration in your general condition require urgent medical attention.

Specialists involved

HIPEC forms part of a specialised care pathway in which it must first be determined whether there is a peritoneal disease amenable to surgical treatment, what cytoreduction can be performed, and whether perfusion offers any benefit for that specific tumour.

At the Publio Cordón Memorial Hospital, the Peritoneal Carcinomatosis Unit is the unit most specialised in this treatment. It forms part of the Surgical Oncology Department and focuses on managing peritoneal tumour spread through complex cytoreductive surgery and the incorporation of intraperitoneal treatments where indicated.

The Surgical Oncology Department assesses resectability, plans the extent of the surgery and performs the necessary cytoreduction before administering HIPEC. Within this speciality, there are also specific units linked to the tumour of origin, such as the Specialised Ovarian Cancer Unit, which specifically includes cytoreductive surgery with or without HIPEC in selected patients.

Medical Oncology integrates HIPEC into the overall cancer management plan and establishes its relationship with systemic chemotherapy, immunotherapy, targeted therapies and other treatments. The department has specific units for Gastrointestinal Tumours and Gynaecological Tumours, amongst others, which allows the strategy to be tailored to the origin of the disease.

Diagnostic Imaging is involved in assessing the distribution of implants and in pre-operative planning. Pathology confirms the tumour type and provides relevant information both before and after the procedure.

Anaesthetology and Resuscitation is involved in the preparation and perioperative management of surgery that may be lengthy and physiologically demanding. When the clinical situation requires advanced monitoring, Intensive Care Medicine (ICU) is involved in post-operative care.

Endocrinology and Nutrition may be involved in assessing and optimising nutritional status prior to extensive surgery and in supporting subsequent recovery. Nursing, Rehabilitation and other teams are involved depending on the resections performed and the functional needs of each individual.

Not all patients require the involvement of all these departments at every stage. The care pathway is tailored to the primary tumour, the extent of peritoneal disease, the planned surgery, and the patient’s recovery needs and subsequent cancer treatment.

Medical information for general guidance

This factsheet aims to help you understand what HIPEC is, why it is usually administered following cytoreductive surgery, for which tumours it may be considered, how the infusion is carried out, and what role it plays within the overall cancer treatment programme. It also explains its main limitations, risks and alternatives.

At the Publio Cordón Memorial Hospital, we believe it is important that medical information is 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 about 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 factsheet describes the general principles of HIPEC. Its indication must be tailored to the individual patient, taking into account the tumour of origin, the extent of the disease, the feasibility of achieving adequate cytoreduction, the overall cancer treatment plan, the patient’s general condition and the available alternatives.