Breaking Through the Barricade
HIPEC gives physicians opportunity to treat hard-to-reach cancers in the abdomen
by Celia Spell
Walls are designed to do one of two things: contain or keep out. And the peritoneum is no exception. As the serous membrane lining the abdominal cavity and covering the organs within, the peritoneum provides protection from infection as well as storing fat.1 It keeps the organs in place while allowing blood vessels, lymph vessels and nerves to pass through.
It is also extraordinarily effective at keeping everything else out, which makes treating cancer in the abdominal cavity difficult to target with systemic chemotherapy.
This “plasma-peritoneal barrier” isolates the abdomen from the cytotoxic effects of intravenous (IV) treatment. Poor intraperitoneal blood supply then causes poor oxygenation of the cancer cells, which in turn results in hypoxic tumors with low levels of apoptosis, or programmed cell death.2 To get around this obstacle, physicians turned to hyperthermic intraperitoneal chemotherapy (HIPEC) to treat cancers within the abdominal cavity.
“Our goal is to surgically remove all of the disease that we can,” said Ramsay Camp, M.D., FACS, a surgical oncologist at MUSC who performs these procedures with Virgilio George, M.D., a gastrointestinal surgeon at MUSC. “And then use HIPEC to treat residual cells that we can’t see throughout the whole abdomen.”
HIPEC was developed in the 1990s for patients whose cancer had metastasized to the peritoneum, a progression with a poor prognosis. Researchers studying colorectal cancer found that surgically removing the tumors resulted in a 21-32% 10-year survival rate, with only 3-12% of patients remaining free of disease, but when surgery was combined with HIPEC, the 10-year survival rate climbed to 60-80%, and 55-74% of patients were free of disease.3
Primary colorectal cancer, ovarian cancer, gastric cancer, appendiceal cancer, mesothelioma and peritoneal carcinomatosis can be treated with HIPEC as long as they are contained in the peritoneum.
“The combination approach provides the only chance for long-term survival in patients with these diseases,” said George.
After cytoreductive surgery, the physician team treats the patient with a heated sterile chemotherapy solution, which can be administered via an open or closed technique; Camp and George deliver the solution to their patients by using the closed technique. They place inflow and outflow catheters throughout the abdomen and then temporarily close the incisions around them with a watertight seal that keeps the perfusion inside a closed circuit. The chemotherapy solution is then heated to 41-43 degrees Celsius, as studies have shown that the benefits stem from a solution that is warmer than the patient’s body temperature.3
Once the solution temperature reaches 41 degrees, it activates selective cytotoxicity on the tumor cells, which allows the heated drugs to destroy any remaining microscopic cancer cells. The heat also activates protein degradation in these cells, which stops oxidative metabolism while increasing the cell’s pH levels. These changes activate the lysosomes and encourage apoptosis.4 The heat also compounds the cytotoxic effects of the chemotherapy and helps with absorption.
Using a HIPEC perfusion system to maintain a consistent temperature and push three to five liters of the solution through the catheters into the abdomen, chemotherapy is circulated throughout the patient’s peritoneum for 90 minutes.
Physicians monitor the patient’s internal temperature throughout the procedure to ensure that the core does not become too warm with the infusion of heated chemotherapy. Camp said his team generally uses a cooling blanket to avoid overheating, but they have used ice and cool IV fluids as well. After perfusion, the surgical team reopens the sutures and performs any necessary anastomoses.
HIPEC offers a solution for patients with peritoneal metastasis by delivering a higher concentration of the drug while being less toxic due to the same plasma-peritoneal barrier that makes this location hard to treat. The barrier confines chemotherapy exposure locally, allowing HIPEC doses that are 20-50 times more concentrated than those for traditional systemic chemotherapy.3 Side effects from the procedure usually stem from the magnitude of the cytoreductive surgery rather than the exposure to the solution.5
HIPEC in conjunction with cytoreductive surgery involves a coordinated effort between multiple teams to remove the tumors and administer the heated chemotherapy. Because of the complex nature of this treatment, HIPEC is usually only performed at tertiary care centers in the U.S. “We are excited to no longer have to send patients outside the state,” said Camp. “We can perform it right here at MUSC.”
References
1. Jacquet P, Sugarbaker PH. Peritoneal-plasma barrier. In CTAR, vol 82. Boston, MA: Springer; 1996:55-63.
2. Seshadri RA, Glehen O. World J Gastroenterol. Jan 2016. doi:10.3748/wjg.v22.i3.1114.
3. Hall B, et al. Surg Clin North Am. 2017;97(3):671-682. doi:10.1016/j.suc.2017.01.013.
4. Bartos A, et al. Chirurgia. 2019. doi:10.21614/chirurgia.114.2.222.
5. González-Moreno S., et al. World J Gastrointest Oncol. 2010;2(2):68-75. https://www.wjgnet.com/1948-5204/full/v2/i2/68.htm.
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