Overview of Cytoreduction (CRS) and Hyperthermic Intraperitoneal Chemotherapy (HIPEC)
Peritoneal carcinomatosis, a type of tumor infiltration of the lining of the abdomen (the peritoneum), most often happens when someone has tumors in their abdominopelvic area, such as gastrointestinal or gynecological cancers. These types of tumors can spread into the lining of the abdomen. This can happen with tumors that are advanced, mucosal (affecting the lining of a body cavity), tumors that have perforated (made a hole), or tumors that have been opened during surgery.
In colorectal cancer, the peritoneum is the second place the cancer is most likely to spread to. Unfortunately, it’s associated with a poor outlook, with survival typically around 6 to 9 months without treatment. Roughly 5% to 10% of people with colorectal cancer will experience peritoneal carcinomatosis.
Ovarian cancer also frequently presents with peritoneal carcinomatosis. Around the globe each year, 240,000 women are diagnosed with ovarian cancer. The majority of these cases (90%) are due to a type called epithelial carcinomas. Because ovarian cancer often isn’t found until it has spread to the peritoneum, it’s classified as a peritoneal surface cancer.
It’s important to distinguish peritoneal carcinomatosis from other types of cancers that also spread to the peritoneum, like gastrointestinal or ovarian cancer. The outlook generally isn’t good, with a typical survival of around 6 months for colorectal cancer and 3 months for stomach cancer. These numbers are similar even with chemotherapy. However, the outlook for ovarian cancer is better, with a typical survival up to 2 years.
Treatments usually involve some combination of chemotherapy before the surgery, surgery to remove as much of the tumor as possible, and a heated type of chemotherapy during the surgery (hyperthermic intraperitoneal chemotherapy).
The surgery attempts to remove as much of the cancer as possible, which could involve removing parts of multiple organs. Reduced tumor size is essential for the best outlook. But not all tumors can be fully removed. Medical professionals use an index called the PCI (index of peritoneal carcinomatosis) to understand how much tumor is present, and whether it will be possible to improve survival by surgical tumor reduction. However, if the cancer has spread to certain areas like the root of the mesentery, the liver, behind the abdomen, the bladder, or there’s a risk of major damage to the small intestine that could cause short bowel syndrome, then surgery wouldn’t be a reliable option.
One increasingly popular therapy is hyperthermic intraperitoneal chemotherapy, which involves delivering chemotherapy drugs directly into the abdomen at a higher temperature (41 to 43 degrees C or 105 to 109 degrees Fahrenheit). It was first experimented on animals by a scientist named Spratt in 1980 and is now a standard part of the treatment for primary and secondary peritoneal tumors. This treatment is used a lot for peritoneal metastases – cancer spread from ovarian, stomach, or colorectal cancers.
In recent years, a combination of surgical tumor removal and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) has improved the outcome for patients with tumors of the abdominal lining (mesothelioma), appendix, colorectal, and ovarian cancers. This therapy is an important part of the comprehensive approach to treating these types of tumors.
Anatomy and Physiology of Cytoreduction (CRS) and Hyperthermic Intraperitoneal Chemotherapy (HIPEC)
The size and spread of a tumor inside the abdomen significantly affects the possibility of surgery and the possible outcomes. To judge the size of a tumor, doctors use the Sugarbaker Peritoneal Carcinosis Index, where the abdomen is divided into 12 sections. The size of the tumor in each section is then measured.
When cancer-fighting drugs are given directly into the abdomen, there’s usually a difference in the amount of the drug in the abdomen compared to the amount in the bloodstream. This is because the drug moves from the abdomen to the blood slowly, and there’s a kind of barrier between the abdomen and the blood that affects how fast the drug can move. Interestingly, removing the diseased part of the abdomen doesn’t seem to affect how the cancer drug acts in the body.
The blood from the lining of the abdomen flows toward the liver, which means liver micrometastases (very tiny collections of cancer cells), could be exposed to higher levels of the cancer drugs. Furthermore, cancer drugs can also reach the body’s lymph system, where they are carried to other parts of the body, providing another benefit of delivering chemotherapy in this way.
Some experts refer to a model that considers the tumor-bearing lining of the abdomen as a separate compartment, where the drug is carried in by penetrating the tissue.
The use of heat–known as hyperthermia–is warranted because cancer cells are particularly destroyed by heat around 41 to 43 degrees celsius. Interesting to note, the small blood vessels in most cancerous tumors completely stop in response to heat. Pairing the heat with cancer drugs results in a more potent cancer-killing effect due to an increase in how much the drug gets into the cancer cells. The heat makes the cells more permeable, meaning the drugs can get into the cells more easily. This effect is observed with several chemotherapy drugs including doxorubicin, platinum-containing drugs, mitomycin C, melphalan, docetaxel, irinotecan, and gemcitabine.
Why do People Need Cytoreduction (CRS) and Hyperthermic Intraperitoneal Chemotherapy (HIPEC)
When a patient is being considered for surgery, certain factors are taken into account like how fit they are for the operation, their overall health, how well their liver and kidneys are working, and the amount of chemotherapy they’ve gotten.
For patients with gastric adenocarcinoma, a kind of stomach cancer, a condition called peritoneal carcinomatosis is common. This is when the thin layer of tissue that lines the abdomen and covers most of the organs in the abdomen gets cancer. To help slow the spread of the cancer, a procedure called cytoreduction surgery with CHIP may be done. This operation removes as many tumors as possible then follows up with a heated chemotherapy treatment. However, this treatment does not impact how long the patient might live and is used more for patients under 60 who are active and meet certain criteria.
In ovarian cancer cases with peritoneal carcinosis, a literature review has found that overall survival is increased up to eight years following the cytoreduction surgery with HIPEC.
As for colorectal cancer, peritoneum is the second most common site for cancer to spread. Synchronic PC (cancer present in the peritoneum at the same time as the colorectal cancer) is seen in 7 to 15% of colorectal cancer patients while 4 to 19% develop cancer in the peritoneum later. Since adding HIPEC surgery to chemotherapy treatment, patients have seen a better prognosis.
In cases of peritoneal pseudomyxoma and mucinous tumors of the appendix, a procedure called cytoreduction surgery (CRS) with HIPEC is often used. This technique, which involves removing cancerous cells and then applying chemotherapy, has been the only treatment option for these types of tumors.
In cases of mesothelioma, a rare form of cancer that affects the lining of the abdomen, adding HIPEC to cytoreduction surgery can help to extend how long a patient might live by up to 4 years, although multiple procedures may be needed.
When a Person Should Avoid Cytoreduction (CRS) and Hyperthermic Intraperitoneal Chemotherapy (HIPEC)
Several research studies have found that if all of the tumors cannot be surgically removed, a treatment called Hyperthermic Intraperitoneal Chemotherapy (HIPEC) may not extend a patient’s lifespan.
Additionally, health factors like serious heart conditions, lung disease, liver failure, and kidney failure can complicate HIPEC and may make it too dangerous to perform.
If a patient is allergic to drugs used to kill cancer cells (cytotoxic agents), they should not undergo HIPEC.
There is a scoring system used to help doctors decide if a patient should have HIPEC for colorectal cancer. This score is called the Peritoneal Cancer Index (PCI). If a patient’s PCI is above 20, they typically are not a good candidate for HIPEC. This is because the survival rate after five years is close to zero for those patients.
Surgery may also not be the best choice if a patient’s PCI score is too high or if cancer has spread to areas that are difficult to reach confidently with surgery. These areas include the base of the intestine, the liver, the tissue on the back wall of your abdomen (retroperitoneum), and the bladder. If the small intestine, which helps to digest food and absorb nutrients, is not working properly, this could result in a condition called short bowel syndrome. In that case, HIPEC may also be not recommended.
Overall, the aim of surgery combined with HIPEC is to remove as many tumors as possible. Then, HIPEC aims to destroy remaining cancer cells not visible to the surgeon. This is done by creating a high concentration of chemotherapy in the affected area, while keeping the amount in the rest of the body low.
Equipment used for Cytoreduction (CRS) and Hyperthermic Intraperitoneal Chemotherapy (HIPEC)
Before having this treatment in a hospital, it’s essential to ensure the hospital has the right facilities. These include a setup that can approve and supervise chemotherapy treatments, surgical facilities, and a specialized unit for keeping an eye on patients after surgery.
This procedure, known as HIPEC, can be carried out either with your abdomen open or closed. In either case, a special solution that fights cancer cells (cytostatic solution) is continuously pumped into your abdomen. It’s warmed up to a temperature between 41 to 43 degrees C, using a special drainage system made up of tubes that both put the liquid in and take it out (inlet and outlet catheters).
Carrying out this procedure needs the following equipment:
* A device that swaps heat (a heat exchanger) connected to a temperature controller (a thermostat). This keeps the temperature steady at 42 degrees in the system that circulates the solution outside your body (extracorporeal circulation).
* A set of tubes (inflow and outflow catheter) that adds the cancer-fighting drug to your abdomen and helps it to be absorbed.
* Probes that measure temperature. These keep a check on the temperature in the system and inside your abdomen (the peritoneum).
* A pump (roller pump) that keeps the drug circulating outside of your body.
* A place to hold the cancer-fighting drug.
* A computer system that controls the temperature and the drug’s circulation based on readings from the temperature probers.
* A timer that records how long the drug has been infused for.
There are several drugs that your doctor may use for this treatment. These include mitomycin C, Platine, doxorubicin, paclitaxel, and irinotecan.
These drugs are mixed with a liquid (mainly 0.9% NaCl or 5% glucose) to help them get into your body. The amount of this liquid used is calculated based on your body’s surface area. Normally, volumes between 1.5 and 2 liters per square meter of body surface area are used.
Who is needed to perform Cytoreduction (CRS) and Hyperthermic Intraperitoneal Chemotherapy (HIPEC)?
HIPEC stands for Hyperthermic Intraperitoneal Chemotherapy, a specialized procedure where heated chemotherapy drugs are administered directly into the abdominal cavity. This should only be done by doctors who have specific training in cancer surgery. The nurses in the operating room also need to be specially trained in cancer care, especially in the safe handling and administration of these powerful chemotherapy drugs during the procedure.
The pharmacists at the hospital have an important role as well. They are responsible for preparing these chemotherapy drugs, usually in a designated room with a continuous filtered breeze, also known as laminar flow, to prevent any harmful germs from contaminating the chemotherapy drugs.
Preparing for Cytoreduction (CRS) and Hyperthermic Intraperitoneal Chemotherapy (HIPEC)
Before starting the treatment, it’s important to have a thorough check-up as per the guidelines set by the World Health Organization (WHO). This check-up should include a review of your past medical and surgical records, understanding the spread of the cancer tumor, checking your past treatments like chemotherapy, and also heart and lung tests. Your current treatment and medication, especially blood thinners, should also be reviewed. This is to make sure your risk of bleeding is reduced during the complex surgery coming up, which is part of a treatment known as HIPEC (Hyperthermic intraperitoneal chemotherapy).
You, the patient, need to be fully aware of the pros and cons of this operation, as well as how HIPEC can benefit you and the potential risks involved. This is because this procedure should ideally enhance your chances of survival as a cancer patient. It’s essential that you’re provided a comprehensive explanation of the procedure to fully understand and then give your consent.
An anaesthetist, a medical professional who gives anaesthesia, plays a key role during the cytoreduction (surgery to remove as much of the cancer as possible) and HIPEC. It’s desirable they have specific training for this procedure.
Lastly, this procedure should only be performed at a specialized university medical center equipped with expertise in cancer treatment and surgery, and having the necessary medical monitoring facilities in place.
How is Cytoreduction (CRS) and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) performed
Two approaches that doctors use to treat certain types of cancer are called open abdomen therapy and closed abdomen therapy.
In the open abdomen method, initially described by a doctor named Sugarbaker, doctors make an incision and insert a particular kind of catheter (a type of thin tube) and suction drains to the targeted area. Temperature monitors are also used. The skin around the incision is kept open using a retractor, a tool that keeps a place open in the body. A plastic sheet is also used to prevent any leakage of the chemotherapy solution.
During this procedure, doctors constantly adjust the perfusion (the process of delivering the chemotherapy to a specific area) to ensure all the targeted areas are well exposed to the heat and chemotherapy. A special pump is used to get the chemotherapy into the abdomen and take it out through the drains. The solution inside the abdomen is kept warm at around 41-43 degrees Celsius. After the chemotherapy is delivered, a timer is started. The duration varies from 30 minutes to an hour, depending on the type of cancer.
The downside of this open method is the problem of heat loss, which makes it harder to keep the abdomen warm.
The closed abdomen technique follows similar steps. The only difference is that the skin around the incision is sewn up tightly, allowing the chemotherapy to circulate in a closed area. During this process, doctors have to manually move the abdominal wall to distribute the heat evenly. Compared to the open method, this technique requires a larger amount of solution to establish a closed cycle. This causes an increase in pressure inside the abdomen, which helps the chemotherapy penetrate the tissues more effectively.
The main advantage of this technique is that it manages to maintain a higher temperature since there is minimal heat loss. After the procedure, the abdomen is opened again to remove the solution and prepare for the next steps of the surgery.
Possible Complications of Cytoreduction (CRS) and Hyperthermic Intraperitoneal Chemotherapy (HIPEC)
Recent studies show that a type of cancer treatment combining surgery and heated chemotherapy (HIPEC) can cause health problems in about 33% of cases and result in death around 2.8% of the time. This treatment can be heavy on the body and might make the chemotherapy more toxic because it can change the way your body processes drugs, cause loss of protein, limit liver and kidney activity, and suppress the bone marrow, which is essential for blood cell formation. This increased toxicity might show up as blood disorders (hematotoxicity) and kidney damage (nephrotoxicity) in about 5.6% and 1.7% of cases, respectively.
Some complications linked to this cancer treatment can include difficulty with digestion (prolonged intestinal atony), too much fluid gathering in the belly, slow wound healing, and a lengthy hospital stay. In severe cases of surgery with a torn diaphragm, chemotherapy might even leak into the chest.
There seem to be several factors that increase the risk of serious complications from this procedure. These include the patient’s overall health, their age, how far the cancer has spread in the lining of the abdomen, the duration of the operation, the number of different surgical procedures done to remove the tumors, the number of connections made between separate parts of the intestines, the success of the surgery in removing most of the cancer, and the amount of chemotherapy used inside the belly.
There are also other complications that can occur not solely due to the heated chemotherapy, but are instead linked to the surgery itself. These can include inflammation of the pancreas (pancreatitis), abnormal connections forming between different parts of the body (fistulas), blood clots in the lungs (pulmonary embolisms), and other types of blood clots.
What Else Should I Know About Cytoreduction (CRS) and Hyperthermic Intraperitoneal Chemotherapy (HIPEC)?
Many scientific experiments have shown that when a surgeon works on removing parts of the lining of the abdomen due to cancer, there will inevitably be some cancer cells that are left behind or spread in the process. One of the main aims of delivering chemotherapy straight into the belly is to kill off these stray cancer cells and any tiny spots of cancer that can’t be seen or removed during surgery. This process is typically done after the cancer has been removed and before the surgeon repairs any part of the digestive tract. This approach, combining surgery and directly delivered chemotherapy, is becoming a more common treatment strategy for patients with certain types of cancers in the abdomen.
Many scientific experiments have shown that this approach of combining different treatments is better than just a single form of therapy for treating cancer that has spread.
One study on the treatment of a specific type of ovarian cancer showed a clear benefit of using this combined treatment approach compared to just surgery. Especially, it helped patients live longer.
Similarly, another study conducted over 6 years on 265 patients with a specific type of bowel cancer also showed noticeable benefits. The patients who had chemotherapy delivered into their abdomen after the cancer surgery had better survival rates, particularly those whose cancer had spread to a limited extent.
However, not all cancer centers agree on the way this chemotherapy is delivered into the abdomen, including which drugs to use, how much of the drugs to use, how long to deliver the drugs into the abdomen, what temperature to maintain, how much fluid to use, how long to continue this treatment, and what the best mode of delivery is.
Various studies have confirmed that combining chemotherapy, given either directly into the abdomen or through the veins, with surgery is still beneficial.
However, the benefits of giving chemotherapy around the time of surgery in patients with colorectal cancer that can be removed is still a topic of ongoing debate. A recent study showed no clear benefit of this treatment strategy in patients who were good candidates for surgery and direct chemotherapy to the abdominal cavity for colorectal cancer.
For stomach cancers that have spread to the lining of the abdomen, the outlook is not very good, with an average survival of only 7 months. This survival time may improve to 12 months on average after surgical removal of cancer. Some research studies have shown that adding chemotherapy directly into the belly might help patients live longer.
For a certain type of cancer that spreads within the abdominal cavity and produces a lot of mucus, the combination of surgery and chemotherapy directly into the belly is the only effective treatment. Studies have shown this approach can improve average survival time to up to 16.3 years.
