A better way to treat pancreatic cancer pain

Pain management is one of the most important and difficult aspects of palliative care for inoperable pancreatic cancer. Approximately 90 percent of patients ultimately develop severe or intractable pain that is not alleviated by nonsteroidal anti-inflammatories. Opioids may relieve pain, but are associated with dry mouth, constipation, nausea, vomiting, drowsiness, delirium and impaired immune function.

One well-established alternative to standard therapies is celiac plexus neurolysis (CPN), which chemically interferes with pain transmission via the celiac plexus. The goal is to improve pain control and quality of life and reduce the risk of drug-induced side effects.

CPN has traditionally been performed percutaneously under CT or fluoroscopic guidance, but this approach is limited by a lack of precise visualization of target structures and the need to traverse many tissues on the way to the target region.

More recently, celiac plexus neurolysis has been performed under endoscopic ultrasound (EUS), guidance, which provides better visualization and more precisely targeted therapy. The ability to perform EUS-CPN at the time of tumor biopsy and staging combines diagnostic and therapeutic modalities, simplifies patient care, and reduces cost.

In spite of these advantages, EUS-CPN has limitations, according to Michael J. Levy, M.D., of Mayo Clinic in Rochester, Minn.

"Standard percutaneous and EUS approaches that target the general area of the celiac plexus lead to inaccurate delivery and rapid dispersal of the injectate, which may limit effectiveness and heighten the risks," he explains. A potentially better approach, he says, is to precisely target and inject the celiac ganglia directly, which improves drug delivery and neurolysis and may improve pain relief.

Mayo Clinic physicians were the first to recognize the ability to use EUS for detection of ganglia and to report their experience performing EUS-guided celiac ganglia neurolysis (CGN).

EUS-guided celiac neurolysis (whether CPN or CGN) is usually performed in the outpatient setting. At Mayo, contraindications include uncorrectable coagulopathy, thrombocytopenia, inadequate sedation and altered anatomy.

During EUS-CGN the EUS instrument is passed through the mouth into the stomach just below the diaphragm. The aorta is traced distally to the celiac trunk, which is the first major branch below the diaphragm. Doppler may be used to distinguish vascular structures. The needle is advanced under careful EUS guidance through the gastric wall directly into celiac ganglia. Neurolysis is performed using 98 percent alcohol and a small amount of lidocaine or bupivacaine to help mitigate a potential increase in short-term pain. The entire procedure adds only five minutes to the EUS exam.

Risks and benefits

Dr. Levy says approximately 75 percent of patients experience partial or significant pain relief and a decreased need for narcotics after EUS-guided neurolysis. Although most cannot stop medications entirely, they may be able to avoid some opioid side effects.

"There is a subgroup that does not respond and it is unclear why," Dr. Levy says. "Age and gender don't seem to play a role. The data are conflicting in terms of response relative to tumor location. We do know that if the tumor directly invades the celiac trunk, neurolysis is less likely to be effective. We also know that pain is multifactorial, which is one reason neurolysis may be ineffective or partially effective."

Paralysis is the most serious complication of celiac neurolysis, and has been reported in 15 patients worldwide since 1914, when the procedure was first performed. In half the cases, the paralysis is reversible. More common problems, such as postural hypotension, diarrhea and pain exacerbation are usually mild and easily treated. Other complications are rare.

Neurolysis trial

According to Dr. Levy, several small studies, including one at Mayo, suggest the superiority of EUS-guided celiac ganglia neurolysis. But these trials included too few patients and the methodology adopted does not allow firm conclusions regarding the relative efficacy and safety of the procedure compared with standard techniques. To better address these questions, Dr. Levy and colleagues initiated a prospective, randomized, double-blind trial comparing EUS-CPN with EUS-CGN for managing pancreatic cancer pain.

The aim is to determine whether EUS-CGN enhances the efficacy of neurolysis and pain relief, improves quality of life, reduces morphine use, and prolongs survival.

Dr. Levy explains, "Studies have established the efficacy of EUS-guided celiac neurolysis within a subgroup of patients, but we need to better understand the demographics of this group. We need to determine which techniques are safest and most efficacious and to identify the factors that predict treatment response. Mainly, we need to determine how best to help our patients who are suffering from pain, which is often the most debilitating symptom in patients with pancreatic cancer."