Heated Intraperitoneal Chemotherapy (HIPEC)
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Heated intraperitoneal chemotherapy (HIPEC) is used after debulking surgery for some patients with peritoneal mesothelioma. Instead of delivering chemotherapy drugs intravenously, HIPEC involves circulating the drugs throughout the abdominal cavity.[1] HIPEC has proven to be one of the most effective treatments for this cancer, greatly improving survival rates.[2]
What is HIPEC?
Typically chemotherapy is a highly effective cancer treatment that treats the whole body. Chemotherapy uses one or more drugs that target and kill fast-growing cells, like cancer cells. For many patients it effectively shrinks tumors. In some cases, it can even lead to remission. Traditionally, chemotherapy drugs are administered intravenously, entering the drug stream directly and then circulating throughout the body. This method kills cancer cells, but can also damage many healthy cells in the process.
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HIPEC is more specific than the traditional administration of chemotherapy drugs. Instead of simply injecting drugs into the bloodstream, the drugs are administered directly into the abdomen, specifically targeting peritoneal tumors. The drugs are heated to increase their effectiveness, and then the abdominal cavity is essentially bathed in the chemotherapy drugs while the patient is still asleep.[3]
The Procedure
HIPEC begins with cytoreductive surgery, which removes as much of the tumors as possible. This is an important step because chemotherapy drugs cannot penetrate deep into the center of tumors. For the chemotherapy to be effective, the bulk of the tumors must first be removed with surgery. Once most of the tumor tissue is removed, circulation of chemotherapy kills cancerous cells that remain in the abdominal cavity.[3] For some patients, tumors may be too numerous to remove with surgery. In these cases, peritoneal chemotherapy will not be as effective.
After surgery, the next step is the heated chemotherapy bath. Even if the surgery removed all visible tumors, microscopic cancer cells may still be left in the abdomen. The goal of this second step is to kill the remaining cancer cells. Catheters are inserted into the abdomen and the abdominal cavity is either left open or the skin is closed.[2] These catheters are connected to a perfusion machine that contains and heats the solution of chemotherapy drugs. The machine then pumps the drugs through the catheters and into the abdominal cavity.
The bath is monitored carefully to maintain a temperature of 108 degrees or a little higher. This temperature is key because cancer cells begin to die in temperatures of 108.[1] However, healthy cells can tolerate temperatures up to approximately 110 degrees. After the solution has circulated through the abdominal cavity, outflow catheters send it back to the machine. This process usually takes a couple of hours.
Chemotherapy Drugs Used
There are many drug options for HIPEC. Research has shown that a combination of drugs more effectively extends life expectancy than using a single drug. Researchers are also attempting to determine which specific drugs are most effective. The most common chemotherapy drugs used effectively in HIPEC procedures are cisplatin, carboplatin, gemcitabine, pemetrexed, and doxorubicin.[4]
One significant advantage to HIPEC is that higher doses of chemotherapy can be delivered within the abdomen with minimal effects on the rest of the body. This allows for better treatment response with less typical side effects of chemotherapy such as hair loss, diarrhea, and mouth sores.[3]
Recovery
Patients undergoing HIPEC will usually remain in the hospital for about seven to ten days; however, complete recovery from HIPEC can take several months. This period includes healed surgical incisions, an absence of infection, and an anticipated return to baseline function.
Surgery may involve the removal of multiple internal organs or bowel resections that are involved with the tumor. The risk of surgical complications, such as bleeding, infection, pneumonia, and blood clots can be heightened.[5]
The chemotherapy drugs are not absorbed in the body, which minimizes the typical side effects, the most common of which is fatigue. It can take several months to regain normal energy levels.[6]
How HIPEC Affects Survival Rates
HIPEC has had a significant effect on the survival of patients with peritoneal mesothelioma. In some cases, patients live five or more years after the procedure. This is a significant improvement over more traditional treatments. One large HIPEC study examined over 400 patients and found the median survival time was between four and five years.[7]
Patients Eligible for HIPEC
Not all patients with peritoneal mesothelioma will be eligible for this treatment. First, the patient must be healthy enough for a complex abdominal surgery. HIPEC is only effective with surgery as the first step.
Another disqualifying factor is extensive spread of the cancer. If tumors have spread outside the abdominal cavity, to the lungs or elsewhere, the procedure will have little effect on patient survival. Healthy patients with no serious comorbid conditions, like heart disease, are excellent candidates for HIPEC treatment.
Benefits and Risks
The most important benefit of undergoing HIPEC is improved survival time. After this treatment, most patients will have an extended life expectancy. When compared to traditional chemotherapy, HIPEC causes fewer, less severe side effects. It also allows for a safer delivery method of a more concentrated, higher dose of chemotherapy drugs.[3] HIPEC also improves quality of life for patients. Once the side effects have dissipated, patients experience reduced cancer symptoms, particularly reduced pain, bloating from fluid accumulation, and bowel obstructions.
There are risks associated with any surgery and chemotherapy. Fifteen percent of patients will experience an infection at the incision site and 10% may develop an incisional hernia. About 15% of patients will experience intra-abdominal complications like fistulas, abscesses, or gastrointestinal leaks related to the surgery. Systemic complications caused by the chemotherapy drugs are also possible, including infections, kidney injury, suppression of bone marrow, and pulmonary problems.
HIPEC and Pleural Mesothelioma
HIPEC has been used to treat peritoneal mesothelioma for some time. Some specialists are adapting the technique for pleural mesothelioma.[8] The procedure, called heated intrapleural chemotherapy, remains controversial. While some studies show extended life expectancy, others find the outcomes related to the chest cavity procedure to be similar to intravenous chemotherapy alone.
Because there are so many blood vessels in the chest cavity, they absorb the chemotherapy drugs from the heated chemotherapy bath. These drugs then circulate with the blood, spreading them through the entire body, just as with intravenous chemotherapy.
Further research into improving HIPEC is necessary and expected to continue as the treatment becomes available to more patients. Experts and researchers hope to continue to advance the treatment strategy, helping more patients live longer after a mesothelioma diagnosis.
Page Medically Reviewed and Edited by Shanel Bhagwandin DO, MPH
Dr. Shanel Bhagwandin is a surgeon with special training in surgical oncology. In 2019 he joined the team at Jupiter Medical Center in Palm Beach County, Florida as the Medical Director of the Gastrointestinal Surgical Oncology Program. He came to Jupiter from Mount Sinai in New York, where he still holds teaching and leadership positions and where he trained alongside experts in complex surgical oncology. Dr. Bhagwandin came to Jupiter to bring HIPEC, a treatment for peritoneal mesothelioma that is not available everywhere, to the patients in the region. He is board certified in general surgery, surgical oncology gastroenterology, and hepato-pancreato-billiary surgery.