Hyperthermic (or heated) intraperitoneal chemotherapy, called HIPEC for short, is a treatment for cancers that begin in or have spread to the thin layer of tissue that lines the abdomen and abdominal organs known as the peritoneum. After a surgeon removes all visible tumors from the abdominal (peritoneal) cavity in a procedure called cytoreductive surgery (CRS), heated chemotherapy drugs are pumped into the abdomen where they bathe abdominal tissues for about 90 minutes before being drained and rinsed from the abdominal cavity. In many cases, the goal of the treatment is to cure patients of cancer by killing any cancer cells that remain after cytoreductive surgery.

HIPEC is used to treat cancers in the peritoneum, including those that have spread—or metastasized—from the gastrointestinal tract, colon, appendix, and ovaries, among other organs, as well as cancerous tumors that started in the peritoneum.

Cancer that originates in the peritoneum is very rare. However, each year, around 60,000 people in the United States are diagnosed with metastatic cancer that has spread to the peritoneum from elsewhere in the body. People with these cancers often experience debilitating symptoms (including abdominal and back pain, nausea, constipation, and fatigue) and can have a poor prognosis.

However, HIPEC, combined with cytoreductive surgery, can improve the outlook for many people with these types of cancers, helping them live longer and with an improved quality of life. For some people, HIPEC can result in a long-term cure. In other cases, with HIPEC, doctors can manage incurable cancers as chronic illnesses rather than as terminal diseases.

“Our entire team is focused on trying to cure Stage IV cancer, while striving for the highest quality of life for our patients,” says Kiran Turaga, MD, MPH, chief of Surgical Oncology for Yale Medicine.

HIPEC is a technique for treating cancers that have originated in or spread to the peritoneum, the thin layer of tissue that lines the abdominal cavity and organs.

It is part of a two-step surgical process. The first step is CRS, which is the surgical removal of all visible tumors from the abdominal cavity.

During HIPEC, the second step of the process, a heated chemotherapy wash is pumped into the abdomen, where it bathes the inner abdominal lining and organs, destroying any cancer cells that remain.

Combining CRS and HIPEC is an aggressive and effective treatment for cancers of the peritoneum, as it allows doctors to remove visible signs of the cancer and kill any cancer cells that remain after surgery.

HIPEC offers the following advantages over traditional chemotherapy:

• HIPEC delivers a concentrated and targeted dose of chemotherapy. In HIPEC, highly concentrated chemotherapy is delivered directly to the inner lining of the abdomen, where it comes into contact with and kills cancer cells. By contrast, traditional chemotherapy is a “systemic” treatment: It is infused into the blood and reaches cancer cells by traveling through blood vessels. Unfortunately, traditional systemic chemotherapy is often ineffective in treating cancers in the peritoneum. This is due, in part, to the peritoneal-blood barrier, which obstructs the delivery of chemotherapy.
• Fewer side effects. Conventional systemic chemotherapy is delivered to cells throughout the body. It kills cancer cells but can also kill healthy cells, resulting in a range of side effects.
  Although this is also true of the chemotherapy drugs used in HIPEC, the side effects are minimized because the peritoneal-blood barrier lowers the amount of chemotherapy that gets absorbed into the bloodstream and transported to cells around the body.
• Improved effectiveness of chemotherapy. HIPEC uses chemotherapy drugs heated to 108° F (42° C). Heating chemotherapy drugs improves their ability to penetrate tissue because the high temperatures expand blood vessels and can increase their effectiveness in killing cancer cells. The heat itself can also kill cancer cells and may make them more susceptible to the chemotherapy.

For some types of cancer, HIPEC is combined with systemic chemotherapy and/or other treatments.

Cancers that may be treated with HIPEC include:

• Appendix cancer
• Colorectal cancer
• Desmoplastic small round cell tumors (DSRCT), a rare, highly aggressive cancer that most commonly occurs in adolescents and young adults
• Malignant ascites
• Mesothelioma
• Ovarian cancer
• Stomach (gastric) cancer
• Other cancers in the abdomen that have invaded nearby tissues

CRS with HIPEC can be performed on adults and children. Although HIPEC is an excellent treatment option for many people, it may not be right for everyone. In addition to having a type of cancer that is treatable with HIPEC, patients must be healthy enough to undergo surgery and chemotherapy treatment.

To determine this, a doctor will review your medical record to learn if you have certain medical conditions that can increase the risk of complications related to the procedure. For example, a doctor may ask whether you smoke or have recently smoked, and check to see if you have a history of cardiovascular disease, diabetes, or other conditions that could increase the risk of complications.

Your doctor will also check your “performance status,” a measure of how well a person with cancer performs everyday activities. You may also need bloodwork and to undergo certain tests to evaluate your heart, lung, and kidney function.

If you’re approved for HIPEC with CRS, you may need to participate in a “pre-habilitation” program prior to surgery. Pre-habilitation programs are designed to prepare patients for surgery and recovery; they may include physical exercise, nutritional counseling, alcohol and smoking cessation interventions, and counseling aimed at helping people better cope with stress and anxiety.

As mentioned above, HIPEC is part of a two-step procedure. First, CRS is performed to surgically remove all abdominal tumors. Then, HIPEC is done to kill any remaining cancer cells.

• Cytoreductive Surgery (CRS). In this first part of the procedure, with patients under general anesthesia, surgeons remove all visible tumors from the abdominal cavity. CRS is often done via open surgery, which requires a long incision in the abdomen. In some cases, for instance, for some early-stage cancers, it can be done using a minimally invasive procedure (known as laparoscopic surgery) that involves small incisions in the abdomen.
• HIPEC. HIPEC, to kill remaining cancer cells, may be performed in two ways:
  • Open abdomen technique. After CRS is complete, the abdomen remains open. A pump infuses a heated chemotherapy solution into the abdomen to bathe the peritoneum and abdominal organs. The surgeon manually stirs the solution during the procedure to ensure the drugs are properly distributed around the abdomen. An outflow line drains the chemotherapy solution out of the abdomen, the abdominal cavity is rinsed, and the skin is then stitched closed.
  • Closed abdomen technique. When CRS is completed, catheters—plastic tubes—are inserted into the abdominal cavity, and the incision is stitched closed. A heated chemotherapy solution is then pumped into the abdominal cavity through the catheters. The surgeon manually shakes the patient’s abdomen to distribute the chemotherapy around the abdominal cavity. After a set period, the abdomen is re-opened, and the solution is drained. The chemotherapy is washed out, and the abdomen is then stitched closed again at the end of the procedure.

For both techniques, the chemotherapy solution is heated to 108° and remains in the abdominal cavity for about 90 minutes. In total, about 3 to 5 liters of chemotherapy solution are used during HIPEC.

After undergoing HIPEC with CRS, patients typically go to an inpatient floor to recover and spend 5 to 7 days in the hospital.

During the first days of recovery, patients may need to empty their bladder through a urinary catheter and may receive fluids. In many cases, though, patients are encouraged to drink clear liquids later on the day they had the surgery and to begin eating solid food the day after the procedure. While in the hospital, patients will begin light physical exercises as part of their recovery. They may also need to take medications to prevent blood clots for several weeks following surgery.

Once patients are discharged, they should continue to see their health care provider for ongoing monitoring of their condition.

Like all surgical procedures, HIPEC with CRS comes with some risk for complications. These can include:

• Bleeding at the surgical site
• Infection
• Perforation of the stomach or intestine
• Intestinal fistula (an abnormal opening in the intestinal tract through which stomach or intestinal contents can leak)
• Blood clots
• Nausea
• Slowed wound healing
• Bone marrow suppression (a reduction in blood cell production)
• Acute kidney injury
• Death, in very rare cases

The outlook varies depending on a number of factors, including the patient’s age, general health, and the type and severity of cancer. In general, younger people who don’t have cardiovascular disease or diabetes and who never smoked are at lower risk for complications.

Research into the effectiveness of HIPEC with CRS is ongoing, but several studies have shown the procedure can help people with many kinds of cancer of the peritoneum live longer and with fewer symptoms. Sometimes, a cure is possible with HIPEC and CRS.

“Our program at Yale is among the very few in the country that seamlessly integrates research, clinical excellence, and kindness to provide the most compassionate and effective care for patients with peritoneal metastases,” says Dr. Turaga. “Each of us comes to work with a single-minded purpose of curing cancer and alleviating the suffering that it causes for patients, their friends, and families.”