Cytoreductive Surgery and HIPEC

Important Facts About Cytoreductive Surgery and HIPEC

• Cytoreduction with HIPEC is a two-part procedure combining surgery and chemotherapy. Cytoreduction is the debulking part of the surgery. Doctors look for and remove all visible tumors from the peritoneal surface and in the abdominal cavity. A peritonectomy is performed, which is the complete removal of the lining of the abdominal cavity.
• HIPEC is an acronym for “hyperthermic intraperitoneal chemotherapy.” The therapy involves delivering hyperthermic, or hot, liquid chemotherapy drugs directly into the abdominal cavity.
• Cytoreductive surgery combined with HIPEC is a time-consuming operation. The entire process can take up to 14 hours.
• Survival rates for this surgery vary. Some cancer centers report an average of 3-5 years of survival following the procedure. Eligible patients have much better life expectancy.

Overview of Cytoreductive Surgery With HIPEC

Cytoreductive surgery plus HIPEC is a comprehensive and specialized medical procedure designed to treat certain cancers within the abdominal cavity. Cytoreductive surgery (CRS) involves the meticulous removal of visible tumors and affected tissue, aiming to reduce the cancer burden to microscopic levels.

This is followed by hyperthermic intraperitoneal chemotherapy (HIPEC), a mesothelioma treatment where heated chemotherapy drugs are circulated within the abdominal cavity to eliminate residual cancer cells. The combination maximizes therapeutic impact by addressing both the visible and microscopic disease, offering improved outcomes for conditions like peritoneal mesothelioma while minimizing systemic toxicity.

Some patients receive a less aggressive and invasive cytoreduction/HIPEC for palliative purposes, which can extend survival by a few months and decrease discomfort from symptoms, such as abdominal fluid build-up (ascites) or tumors pressing against certain organs.

At the Medical College of Wisconsin, 17 cancer patients underwent 20 HIPEC surgeries for palliative reasons. While the average survival was less than one year, symptom management improved and reduced patient symptoms 90% of the time. Symptom relief was reduced or permanently resolved after HIPEC surgery for an average of 5.1 months.

Where Was Cytoreductive Surgery/HIPEC Developed?

Cytoreductive surgery with HIPEC is also referred to as CRS plus HIPEC or cytoreduction with HIPEC. It was developed at the end of the 20th century, thanks in large part to mesothelioma specialist Dr. Paul Sugarbaker of the Washington Cancer Institute. Dr. Sugarbaker’s influence on the development of this surgery is why it’s often called the “Sugarbaker Technique.”

Cytoreduction surgeries have existed since the middle of the 20th century. Dr. Joe Meigs at Massachusetts General Hospital in Boston first reported using tumor debulking surgery for the treatment of ovarian cancer in 1934. However, the procedure did not become widely used until the 1970s. Doctors began introducing intraoperative chemotherapy for abdominal cancer treatment in the 1970s and 1980s.

PAVING THE WAY FOR NEW TREATMENT & DIAGNOSIS

The development of cytoreductive surgery and heated intraperitoneal chemotherapy for peritoneal mesothelioma began in the 1990s. During this decade, Dr. Sugarbaker and colleagues introduced the Peritoneal Cancer Index (PCI) to stage new cases of malignant peritoneal mesothelioma and determine patient eligibility for safe surgery.

In 1995, Dr. Sugarbaker introduced the surgical procedure called peritonectomy to the cytoreduction portion. Peritonectomy is a precise technique to remove sections or the entire peritoneal (abdominal) lining to address cancers or diseases that involve the abdominal cavity.

Cytoreductive Surgery

Cytoreductive surgery is a highly specialized procedure aimed at manually removing visible tumors from the abdominal cavity, making it the only radical surgical option for patients with peritoneal mesothelioma. The primary goal of this “debulking” surgery is to eliminate all visible tumors and diseased tissue within the abdomen, although microscopic cancer cells may still remain.

During the mesothelioma surgery, surgeons often remove the omentum, which is a layer of fatty tissue covering the abdominal organs. Doctors also remove the entire peritoneum, which is the membrane lining the abdominal cavity.

Depending on the extent of the disease, other organs may need to be partially or completely removed if tumors are inseparable from the organ’s surface and removal poses no significant health risks. Organs that can be safely removed include the gallbladder, spleen, and sections of the small or large intestine, ensuring comprehensive tumor reduction while prioritizing patient safety.

An article published in JAMA stated surgeons may remove the pancreas, kidney, ureter, bladder and uterus without increasing severe complications or mortality rate.

HIPEC

HIPEC, or hyperthermic intraperitoneal chemotherapy, is a cutting-edge intraoperative treatment designed to target and kill peritoneal mesothelioma cancer cells.

Often referred to as “hot chemotherapy,” this technique has significantly improved outcomes for patients with this rare and aggressive disease. HIPEC involves delivering chemotherapy drugs directly into the abdominal cavity, reducing many of the side effects commonly seen with systemic (intravenous) chemotherapy.

During the procedure, doctors prepare a heated chemotherapy solution, often using drugs like cisplatin or carboplatin, with additional options including doxorubicin or mitomycin, depending on the case. The solution is heated to a precise temperature to enhance its cancer-fighting properties and circulated throughout the abdominal cavity for about 60-90 minutes.

Following the infusion, the chemotherapy drugs are drained, and the abdominal cavity is flushed with a sterile saline solution to remove any remaining chemotherapy agents. Despite its complexity, HIPEC is a vital component of treatment for patients with peritoneal mesothelioma, offering a targeted and effective approach to managing the disease.

What Is the Peritoneum?

The peritoneum is a layer of mesothelial tissue that lines the entire abdominal cavity and covers the abdominal organs. Composed of fluid and mesothelial cells, it serves as a protective barrier for the organs within the abdomen and aids in maintaining their proper function.

The peritoneum has two distinct tissue layers: the parietal peritoneum, which lines the walls of the abdomen and pelvis, and the visceral peritoneum, which wraps around the abdominal organs. Between these two layers lies the peritoneal cavity, a space filled with a lubricating fluid that reduces friction and allows the tissue linings to glide smoothly against each other. This fluid also allows the abdominal organs to move freely within the cavity, facilitating their proper function.

When tumors develop in either tissue layer of the peritoneum, this is called peritoneal mesothelioma. The tumors can disrupt the normal functioning of the abdominal cavity. As the tumor grows, they occupy space within the cavity, leading to symptoms such as abdominal pain, bloating, and loss of appetite.

What Happens During a Cytoreductive Surgery/HIPEC?

Cytoreductive surgery and intraperitoneal hyperthermic chemotherapy is a long, complex surgery. Prior to incision, the patient is given anesthesia and closely monitored throughout the surgical procedures. The patient is properly positioned for surgery to ensure a safe surgical experience.

CRS and HIPEC for malignant peritoneal mesothelioma can take up to 14 hours. The extent of the cancer determines how long the surgery takes.

The Process of Cytoreduction with HIPEC

If the patient is scheduled to receive dwell chemotherapy as an adjuvant (post-surgical) treatment, doctors will leave the catheters in the abdomen at the end of the surgery. These catheters will provide direct access into the abdominal cavity and offer a path to administer additional chemotherapy treatments to that area.

Closed-Abdominal HIPEC Versus Open-Abdominal HIPEC

There are two main techniques for HIPEC:

• Closed-abdominal HIPEC prevents heat from escaping the abdominal cavity and increases the effectiveness of the drugs. It also prevents drug spillage or leakage from the abdominal cavity since the incision is closed. This aids in drug penetration into the tumors.
• Open-abdominal HIPEC offers good chemotherapy drug distribution. This washes the abdominal cavity with the liquid and reaches hidden crevices. However, drug leakage and heat loss are concerns.

The choice between closed-abdominal HIPEC and open-abdominal HIPEC depends on several factors:

Both methods are effective, and outcomes largely depend on achieving complete cytoreduction and ensuring uniform exposure of peritoneal surfaces to the heated chemotherapy.

Who Can Get Cytoreduction/HIPEC for Peritoneal Mesothelioma?

Patient eligibility for cytoreduction followed by hyperthermic intraperitoneal chemotherapy depends on a few factors. The first is the PCI score, as this score summarizes the extent of the tumors present in the abdomen, how far the tumors have spread and if the tumors have infiltrated to the abdominal organs.

Other factors affecting who can have this surgery are:

Physical health

Age

Cell type

Cytoreduction With HIPEC Eligibility: PCI Score

A patient’s PCI score is a significant factor in determining if a patient is a candidate for cytoreductive surgery. PCI is a numerical scoring system used to quantify the tumor burden in the peritoneal cavity. This score is an important measuring tool used to evaluate how far the tumors have spread in the abdominal cavity. If the cancer is too advanced, surgery won’t remove enough of the disease to improve the patient’s life expectancy.

Peritoneal mesothelioma specialists have different opinions on what PCI score is too high to operate. Dr. Shanel Bhagwandin, from Jupiter Medical Center, said scores higher than 20 often don’t qualify for surgery.

“In terms of the research out there and advances that we’ve made looking at patients who benefit from this procedure, traditionally, if you have a score that’s higher than 20, usually the patient won’t respond well to surgery,” he said. “It usually means they have more disease than can be affected by surgery without all the associated risks.”

Dr. Shanel Bhagwandin

Peritoneal Mesothelioma Specialist

Cytoreduction With HIPEC Eligibility: Physical Health

Physical health is an important factor in eligibility for invasive surgery. Since cytoreduction with HIPEC involves an open abdominal surgery, removal of tissue and organs, and the use of heated chemotherapy, patients must be strong enough to withstand anesthesia, postoperative recovery and postoperative pain.

If the patient has a concerning medical history or lingering health issues, surgeons may avoid aggressive treatment. Operating on patients in poor health can cause severe complications.

Cytoreduction With HIPEC Eligibility: Age

Cytoreductive surgery and perioperative intraperitoneal chemotherapy is an aggressive treatment for peritoneal mesothelioma. This procedure would be difficult for most patients, but especially challenging for older patients. Younger patients with this rare cancer are more likely to be in better overall health and able to tolerate the procedure and recover from this surgery.

Alexis Kidd, a peritoneal mesothelioma survivor of more than 13 years, received cytoreductive surgery with HIPEC in her late thirties. The average age for peritoneal mesothelioma patients is between 50 and 60.

“Because I was younger and healthier, they were able to be aggressive when treating me.”

Alexis Kidd

Peritoneal Mesothelioma Survivor

Older patients — those in their sixties, seventies or eighties — may still qualify for the HIPEC procedure, but the selection process would need to determine if cytoreduction plus HIPEC was possible. It is important to discuss all treatment options with a mesothelioma specialist.

Cytoreduction With HIPEC Eligibility: Cell Type

Mesothelioma cell type is another important aspect in determining eligibility for surgery. Epithelioid mesothelioma cells are easier to treat, due to being the easiest to identify and remove. Sarcomatoid cells grow and spread faster than other cell types, which makes it more difficult to identify and treat.

Some surgeons may choose to be more aggressive and only accept patients with the epithelioid cell type. Sarcomatoid and biphasic mesothelioma types are still considered for surgery but present a more challenging surgical candidate. Specialists may choose other treatment alternatives in the management of their disease.

Epithelioid cells account for 75% of peritoneal mesothelioma cases. This is good news for patients seeking to be treated with CRS plus HIPEC.

Possible Complications From Cytoreductive Surgery With HIPEC for Peritoneal Mesothelioma

Patients may experience complications from cytoreductive surgery and HIPEC. Many are related to the digestive tract:

• Gastrointestinal problems (bowel blockage, nausea and vomiting)
• Small perforations of the bowel (a hole in the stomach, small intestines or colon)
• Intraperitoneal abscesses (infection with collections of pus in the abdominal cavity)
• Pancreatic fistulas (leakage of pancreatic fluid into the abdominal cavity)
• Gastroparesis (paralysis of the stomach – food not being pushed down into small intestines)
• Pleural effusions (fluid surrounding the lungs)
• Pneumonia
• Infections

Risk factors for complications during or after cytoreduction/HIPEC surgery include:

• High PCI score: A high PCI score indicates an extensive tumor burden and more complex surgery.
• Patient comorbidities: Patients who suffer with conditions like diabetes, cardiovascular disease, or malnutrition are at an increased risk of complications following surgery.
• Advanced age: Patients above 60 years old are more prone to postoperative complications.
• Prolonged surgical procedure: This increases the risk of infections, blood loss, and possible organ dysfunction.

Mesothelioma Recurrence After Cytoreduction With HIPEC

A report in the Journal of Gastrointestinal Oncology assessed that most mesothelioma patients will have recurrence after HIPEC surgery. It occurs within the abdominal cavity in up to 57% of patients.

Recurrence can occur locally within the peritoneal cavity or systemically, depending on factors such as the initial tumor burden (PCI score), completeness of cytoreduction, and tumor biology. Patients with recurrent disease may be considered for additional treatments, including repeat CRS with HIPEC, systemic chemotherapy, or palliative care, depending on their overall health and the extent of the recurrence. Regular monitoring with imaging and tumor markers is essential to detect and manage recurrence early.

A second surgery can improve the already elevated survival times for this operation:

• A 2014 study of 65 patients reported a median survival of nearly 4 years
• In 2015, a study of 44 patients reported a median survival of 4.5 years

Mortality Assessment of Cytoreductive Surgery With HIPEC

Researchers from the University of Nebraska-Omaha Cancer Center reported a 30-day mortality rate of 1.1% for cytoreduction with HIPEC. This was much lower than the mortality rates for these other major surgeries:

• Tri-segmental hepatectomy (surgery that removes all or part of the liver)
• Right lobe hepatectomy (surgery that removes one lobe of the liver)
• Pancreaticoduodenectomy, also known as a Whipple procedure (surgery that removes cancer of the head of the pancreas – removing the head of the pancreas, the first part of the small intestine, the gallbladder and the bile duct)
• Esophagectomy (surgery to remove all or part of the esophagus)

Specialists Who Perform Cytoreductive Surgery With HIPEC for Peritoneal Mesothelioma

There is a long list of doctors who perform cytoreductive surgery followed by HIPEC. There are surgeons in each region of the country who specialize in peritoneal mesothelioma. They work at the top cancer centers in the world, with vast resources at their disposal.

Some of the top mesothelioma surgeons who perform cytoreductive surgery and HIPEC:

• 

  Dr. James Pingpank

  UPMC Hillman Cancer Center
  (Pittsburgh, PA)

  Contact Dr. James Pingpank

• 

  Dr. Eugene Choi

  Baylor St. Luke’s Health Medical & Houston VA Medical Center
  (Houston, TX)

  Contact Dr. Eugene Choi

• 

  Dr. Edward Levine

  Wake Forest Baptist Cancer Center
  (Winston-Salem, NC)

  Contact Dr. Edward Levine

• 

  Dr. Richard Alexander

  Rutgers Cancer Institute
  (New Brunswick, NJ)

  Contact Dr. Richard Alexander

• 

  Dr. Joel Baumgartner

  University of California-San Diego Moores Cancer Center
  (San Diego, CA)

  Contact Dr. Joel Baumgartner

• 

  Dr. Mecker Moller

  University of Miami Sylvester Comprehensive Cancer Center
  (Miami, FL)

  Contact Dr. Mecker Moller

• 

  Dr. Kamran Idrees

  Vanderbilt University-Ingram Cancer Center
  (Nashville, TN)

  Contact Dr. Kamran Idrees