Hyperthermic Intraperitoneal Chemotherapy

Last updated date: 03-Mar-2023

Originally Written in English

Hyperthermic intraperitoneal chemotherapy

Hyperthermic intraperitoneal chemotherapy

What is Hyperthermic intraperitoneal chemotherapy?

hyperthermic intraperitoneal chemotherapy (HIPEC) is a kind of cancer treatment. The term "hyperthermic" refers to an excessively high temperature. The term "intraperitoneal" refers to inside your abdominal cavity. During your cancer surgery, HIPEC includes heating chemotherapy medications and circulating them into your abdominal cavity (region within your belly). 

Cancer is treated with hyperthermic intraperitoneal chemotherapy (HIPEC). It entails heating chemotherapeutic medicines and passing them through your abdomen. If you have advanced cancer in your abdomen, HIPEC may be a possibility. During therapy, your surgeon will remove tumors before using HIPEC to attack cancer cells that are not visible to the naked eye.

The delivery of large dosages of chemotherapy into the abdomen to treat cancer that has progressed beyond the organ from which it started is known as hyperthermic intraperitoneal chemotherapy surgery. Traditional chemotherapy can be difficult to treat abdominal malignancies that have progressed to the lining of the abdominal cavity (peritoneum). HIPEC surgery is a more successful method of therapy.


What does hyperthermic intraperitoneal chemotherapy (HIPEC) treat?

Gynecologic malignancies

Peritoneal spread of gastrointestinal (GI) or gynecologic malignancies or primary peritoneal neoplasms is a significant problem for the practicing oncologist because of the poor prognosis associated with these entities and the debilitating effect they have on people who suffer from them.

For selected instances identified with these disorders, cytoreductive surgery coupled with perioperative intraperitoneal chemotherapy is presently a viable therapeutic option. Extensive clinical and pharmacological research investigations have been done, with exceptional therapeutic outcomes, propelling peritoneal surface oncology to the forefront of clinical oncology treatment and research. Furthermore, treatment clinics for peritoneal surface malignancy have been created all over the world.

HIPEC may be used by healthcare practitioners to treat cancers of the abdomen or chest. HIPEC might be used to treat:

  • Appendix cancer, which develops within the appendix (part of the colon and intestines).
  • Colorectal cancer in any portion of your large intestine (colon) or the route between your colon and stomach (rectum).
  • Gastric cancer (stomach cancer), cancer of the inner lining of the stomach.
  • Ovarian cancer, which affects the ovaries, which create eggs and female hormones.
  • Peritoneal cancer, which occurs in the cells lining the abdomen.
  • Mesothelioma, a cancer of the lining of your chest or abdomen caused by asbestos exposure.
  • Soft tissue sarcomas, which are malignancies of the connective tissues.
  • Wilms' tumor, a kind of kidney cancer that primarily affects youngsters.

HIPEC is also a useful palliative therapy for persons suffering with malignant ascites, which is an accumulation of fluid in the abdomen. This is an unintended consequence of having malignancies lining the peritoneum. For certain individuals, a single HIPEC treatment can substitute many paracentesis sessions.


Who is a good candidate for hyperthermic intraperitoneal chemotherapy (HIPEC)?

Radiation Theraphy

HIPEC's benefits are currently being studied by researchers. HIPEC is not used as frequently as other cancer therapies such as surgery, radiation therapy, or standard chemotherapy. The benefit of HIPEC is limited to particular tumors and may not be appropriate for everyone. HIPEC is one method of therapy for people with malignancies of the abdomen and chest cavities. It might be your major therapy choice. Alternatively, it may be used in conjunction with other cancer therapies such as radiation therapy or chemotherapy.

Hyperthermic chemotherapy can help many patients. Your healthcare practitioner will assess the following factors to decide if you are a candidate for HIPEC:

  • If you have any other medical issues.
  • The location of cancer in your abdomen.
  • Your general physical fitness.
  • Your medical history.

HIPEC is primarily used by healthcare practitioners for persons with more advanced (common) abdominal malignancies. For severe abdominal tumors, traditional chemotherapy or radiation therapy is frequently ineffective.


What is the process of hyperthermic intraperitoneal chemotherapy?

Cytoreductive surgery

The initial stage of HIPEC surgery is cytoreductive surgery. Your surgeon will create an incision in your belly while you are sedated to see all visible malignant tumors and damaged tissue.

HIPEC is administered after tumor cytoreduction and before any digestive repair or diversion is performed. The reason for this scheduling in connection to GI tract reconstruction is to limit the possibility of anastomotic or staple line recurrence by exposing bowel segment lines to the chemotherapy solution. Although this is the traditional method, several organizations do anastomoses prior to HIPEC injection with no apparent increase in anastomotic recurrences. The chemotherapy solution is made at the pharmacy and delivered to the operating room in a closed light-protected bag with suitable labelling, which is handled with double gloves and the bag's integrity is examined.

In general, there are two techniques for administering hyperthermic chemotherapy intraperitoneally: open abdomen technique and closed abdomen approach.


Open abdomen technique:

Following the completion of the cytoreductive phase, a Tenckhoff catheter and four closed suction drains are inserted through the abdomen wall and sealed with a purse string suture at the skin. For intraperitoneal temperature monitoring, a varied number of temperature probes fastened to the skin edge may be utilized; at least one in the in-flow line and another at a distance from this point are used.

In order to produce an open area in the abdominal cavity, the skin borders of the abdominal incision are hung up to a self-retaining retractor by a flowing monofilament suture. To avoid chemotherapy fluid splashing, a plastic sheet is integrated into this suture. A slit in the plastic cover is constructed to provide access to the abdomen and pelvis by the surgeon's double gloved hand.

By continuously manipulating the perfusate during the 30-to-90-minute perfusion, all anatomic tissues within the peritoneal cavity are evenly exposed to heat and chemotherapy. With a flow rate of roughly 1 L/min, a roller pump drives chemotherapy perfusion into the abdomen via the Tenckhoff catheter and draws it out via the drains. A heat exchanger keeps the fluid being injected at 43-45°C while keeping the intraperitoneal fluid at 41-43°C.

The perfusate is first recirculated between the reservoir and the heat exchanger to ensure that it is sufficiently heated. Full circulation of the perfusate into and out of the peritoneal cavity is established at this stage until a minimum intraperitoneal temperature of 41.5°C is obtained and maintained.

The medicine is subsequently introduced to the circuit, and the perfusion timer is begun. The intravenous infusion of the necessary medications is also begun at this time period in bidirectional chemotherapy regimens (often referred to as "HIPEC-plus"), while other authors suggest doing it 1 hour before the start of HIPEC.

The fundamental advantage of the Coliseum approach is that hot chemotherapy is evenly dispersed throughout the abdominal cavity, with no temperature or chemotherapy pooling. One downside of the open approach is that heat dispersion makes it more difficult to reach a hyperthermic condition at first. Another potential downside is that operating room employees will be exposed to more chemotherapy.


Closed abdomen technique:

Catheters and temperature probes are implanted in the same manner as in the open approach, but the laparotomy skin borders are sutured watertight so that perfusion is done in a closed circuit. During the perfusion phase, the abdominal wall is manually massaged in an attempt to achieve consistent heat dispersion.

When compared to the open approach, a larger amount of perfusate is often required to form the circuit, and a higher abdomen pressure is generated during perfusion, which may aid drug tissue penetration. The abdomen is reopened after perfusion, and the perfusate is emptied. Appropriate anastomoses are made, and the abdomen is closed in the usual way.

The ability to swiftly produce and sustain hyperthermia due to low heat loss is a significant benefit of the closed approach. Furthermore, the operating room crew is only exposed to the treatment via aerosolized contact. Exposure is only possible by leaking from the surgical incision or catheter wounds.

The biggest problem is the lack of consistent dispersion of the treatment. Because hyperthermia has a restricted therapeutic index, uneven HIPEC dispersion is troublesome. Tumoricidal action occurs at 41-43°C, hence in-flow temperature often reaches 45°C.

As a result of insufficient circulation of heated perfusate, heat and chemotherapy pool and accumulate in dependent parts of the abdomen. This may lead to increased systemic absorption and hyperthermic injury foci, which may contribute to postoperative ileus, bowel perforation, and fistula formation. Certain intraabdominal locations, on the other hand, will be undertreated.

As has been documented in several facilities, cytoreduction and the HIPEC closed approach can be conducted safely. Morbidity linked with this operation includes, as with the open approach, myelosuppression, ileus, and fistula. The presence of heterogeneous distribution within the closed abdomen may enhance the likelihood of intra-abdominal problems.


What happens after hyperthermic intraperitoneal chemotherapy?

After chemotherapy

You'll be in intensive care for about two days after surgery. Doctors and other medical personnel will examine you for fluid loss and test your electrolytes and blood glucose levels.

If your blood sugar level becomes too high, it might impair wound healing, increase infection risk, and create other complications. Antibiotics will almost certainly be prescribed to assist prevent infection. And you'll be given pain medicines while the surgical incision heals, presumably in the form of an epidural.

In terms of eating, you may begin with IV nourishment, but the aim is for you to take solid meals as soon as feasible. This will help you return to regular bowel function quickly. When you leave critical care, you'll stay in the hospital for another 6-20 days on average to continue mending.

You will see your oncologist (cancer specialist) in one to two weeks after you come home from the hospital. Depending on the amount of your operation, recovery might take four to twelve weeks. Your oncologist will continue to monitor your cancer on a regular basis. In certain cases, no more chemotherapy is necessary. In some cases, extra IV chemotherapy is advised. Again, your doctor will determine this.


How effective is hyperthermic intraperitoneal chemotherapy?

Nuclear Medicine

There are multiple benefits of the cytoreductive surgery + HIPEC technique that demonstrate that it is the best technique to treat patients with cancers previously mentioned, increasing their survival and chances to cure. According to the study “Hyperthermic Intraperitoneal Chemotherapy in Ovarian Cancer” carried out in patients with stage III ovarian cancer, people who received cytoreduction plus HIPEC, had an average of 11.8 months more life than the group of patients treated without HIPEC. Also, cytoreduction surgery +/- HIPEC achieves 5-year average survival in cancers of colorectal origin, with the cure of up to 16% of these patients, and over 10 years in cases of ovarian cancer.

HIPEC surgery delivers massive doses of chemotherapy straight into the belly, where regular chemotherapy treatments cannot reach. This novel method has the potential to enhance long-term results and give more therapeutic alternatives for patients with inoperable or advanced stage cancer.

HIPEC has certain advantages over standard chemotherapy. HIPEC has the following advantages:

  • Less harmful side effects since 90% of chemotherapy medicines remain in the belly.
  • A higher dose of chemotherapy, which can kill more cancer cells.
  • One therapy session rather than several treatments over several weeks.

High localized concentrations of cytotoxic medicines can be produced after intraperitoneal administration while keeping systemic drug levels low. The difference in concentration is due in part to the comparatively sluggish rate at which the medication moves from the peritoneal cavity into the plasma (peritoneal clearance). The presence of a peritoneal-plasma barrier, which maintains a constant high concentration gradient of chemotherapeutic medication between the peritoneal cavity and the plasma compartment, explains this pharmacologic benefit.

Another advantage of intraperitoneal chemotherapy delivery is that blood drainage of the peritoneal surface travels via the portal vein to the liver, resulting in a first-pass (detoxifying) impact and greater exposure of possible hepatic micro-metastases to cytotoxic medicines.

There is a wealth of experimental and clinical evidence indicating that hyperthermia in the 41-43°C range preferentially destroys cancer cells. The cellular and molecular basis of this selectivity has been thoroughly investigated. While heat causes reversible and nonselective inhibition of RNA production and mitotic arrest, it causes a selective increase in the number of lysosomes and lysosomal enzyme activity in malignant cells.

Heat and cytotoxic medications frequently result in more cytotoxicity than would be expected from an additive effect. The synergism between the two types of therapy is reliant on a number of variables, including higher drug absorption in malignant cells as a result of increased membrane permeability and better membrane transport.


What are the possible side effects and complications of hyperthermic intraperitoneal chemotherapy?

Chemo side effects

The most common problems include intestinal leakage, renal failure, pancreatic inflammation, sepsis, and a decrease in bone marrow and blood cells. Common side effects such as nausea, vomiting, discomfort, and weight loss normally subside after three months but might linger up to a year. Fatigue, sleep disturbances, bloating, diarrhea or constipation, and depression are all frequent symptoms. One research reported that up to 50% of participants had depression during the first year following HIPEC, however this might have been due to factors other than HIPEC.


Gastrointestinal complications:

The combination of hyperthermia and high-dose chemotherapy utilized in HIPEC may potentially disrupt physiological recovery, increasing the likelihood of anastomotic leaks and GI complications. After CRS and HIPEC, the most prevalent and clinically important GI consequences are small intestinal perforations and anastomotic leaks. Intra-peritoneal abscesses, pancreatic fistulas, biliary fistulas, chyle leak, prolonged ileus, and gastric stasis are further GI problems.

Few studies have attempted to discover predictive markers of GI problems in order to control preoperative surgical risk. The extent of carcinomatosis, duration of surgery, number of GI anastomoses, more than four peritonectomy operations, and perioperative blood loss have all been linked to high morbidity after cytoreductive surgery (CRS) and HIPEC.

Unfortunately, preoperative imaging exploration and decisional models have failed to accurately predict resectability and resection extent. In this context, the most appropriate technique to identify a single patient's post-operative risk is simply reflected by an exploratory laparotomy.


Pulmonary complications:

Pulmonary problems are prevalent following routine abdominal surgery and are the reason for a lengthy hospital stay. Several studies have found that the incidence of pulmonary problems ranges between 10 and 16%.

Peritonectomy of the abdomen diaphragmatic surfaces, as predicted, considerably increases post-operative pleural effusions, especially in the absence of comprehensive thoracic drainage. This method, however, can lower but not eliminate the intrinsic risk of pleural effusion, which is still the second most frequent pulmonary consequence.

Patients having peritonectomy operations are at high risk of post-operative infection complications, with pneumonia occurring in 3.2-10% of cases. Several studies have shown that local experience, improved peri-operative hydration and glucose control, and multidisciplinary care of patients undergoing CRS and HIPEC can minimize pulmonary problems.


Hematological complications:

The reported incidence of hematological toxicity with CRS and HIPEC varies from 4 to 39%. This variation is most likely due to the wide range of agents, duration, temperature, and dilution utilized during HIPEC.

There is little information available on the occurrence of hematological problems following CRS and HIPEC. Mitomycin-C (MMC), the historical medication used during HIPEC surgery, is traditionally linked with neutropenia (4%-39%) and a mortality rate ranging from 0% to 66%. Anemia, obesity, past toxicity to IV chemotherapy, female sex, and MMC dosage in HIPEC are all related with a greater frequency of neutropenia after HIPEC.


Other complications:

Other lower-grade problems that might develop with CRS and HIPEC include renal insufficiency (2-4%), venous thromboembolism (4-4.4%), urinary tract infections, vascular access infections, and so on. The high diversity might be attributed to a variety of variables, including institutional policies, heterogeneity in data collecting and reporting, center experience, and HIPEC protocol variation.


Risk factors for complications:

Several factors, including sex, age, primary colonic anastomosis, number of peritonectomy procedures, number of visceral resections, number of anastomoses, incomplete cytoreduction, disruption of the umbilical fissure, chemotherapeutic agent dose, intra-abdominal HIPEC temperature, and histopathologic grade, have been studied as predictors of moderate to severe morbidity following CRS and HIPEC.



Engaging oncologist

HIPEC (hyperthermic intraperitoneal chemotherapy) is a cancer treatment that includes flooding the abdominal cavity with hot chemotherapy medicines. HIPEC, often known as "hot chemotherapy," is administered after the surgeon has removed tumors or lesions from the abdomen.

Some patients have metastatic cancer that has spread throughout their bodies via the bloodstream. Standard chemotherapy is by far the best option for these individuals. Most of what hyperthermic intraperitoneal chemotherapy treats are intra-abdominal malignancies that, for unknown causes, often metastasis not by entering the bloodstream and spreading to various organs, but by spilling over into the abdominal cavity.

The most common tumors treated by HIPEC are:

  • Colorectal cancers
  • Appendix tumors such as, Pseudomyxoma peritonei and Low-grade appendiceal mucinous neoplasm

Other cancers treated by HIPEC are:

The chemotherapy medication, is heated to 103 degrees Fahrenheit (42 degrees Celsius) and pumped into the abdominal cavity after all visible malignancies have been removed. The patient is placed on a customized cooling blanket to maintain a safe body temperature. Surgeons physically rock the patient on the operating table back and forth for about 2 hours to ensure that the medicine reaches all parts of the abdomen, destroying any cancer cells that remain after surgery and lowering the chance of cancer recurrence.

Hyperthermic Intraperitoneal Chemotherapy provides a number of benefits over traditional chemotherapy:

  • Instead of several treatments over several weeks, it is a single therapy performed in the operating room.
  • 90% of the medication is retained in the abdominal cavity, reducing the harmful effects on the rest of the body.
  • It enables a higher level of chemotherapy.

You will stay in the hospital after treatment to recuperate. Your hospital stay will usually last four to fourteen days. Depending on the nature of your operation, you may be unable to eat or drink anything during your initial recuperation period. You may be given sustenance intravenously (IV) or via a feeding tube.

Potential risks of the HIPEC procedure include paralytic ileus, anastomosis leakage, hemorrhages, infections, pleural effusion, fistulas, abscesses, hematological toxicity, and renal failure. However, when hyperthermic intraperitoneal chemotherapy is conducted in a professional institution, the approach does not pose any more dangers than any other intestinal operation.