EUS-guided CGN for Inoperable Cancer

Study Overview
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Brief Summary
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Patients suffering from pancreatic cancer are associated with a poor prognosis and survival of less than one year is expected in inoperable tumours. Management of these patients would be towards palliation of symptoms. Severe pain occurs in 50 to 70% of the patients and this intractable pain is often difficult to treat. Different pharmacological agents have been used in the past to control this pain and these include non-steroidal anti-inflammatory drugs and narcotic agents. However, patients' responses are often variable and difficult to predict. Furthermore, these agents are associated with their own adverse effects and may further impair quality of life. Celiac plexus neurolysis (CPN) was first described in 1919, since then, different approaches of performing the procedure have been described. The standard technique involves a percutaneous approach but CPN can also be performed by an intra-operative approach with open or laparoscopic means. Results from meta-analysis have shown that CPN was associated with superior pain relief as compared to analgesic therapy alone and reduces the need for opioids analgesics in patients with inoperable pancreatic cancer. Furthermore, CPN causes fewer adverse effects than opioid analgesics and it is the preferred method of improving pain relief in these patients. Recently, endoscopic ultrasonography (EUS) - guided CPN has become popular. The approach is safe and effective and was shown to be associated with long lasting pain relieve in patients suffering from chronic pancreatitis or pancreatic cancer. Serious complications are uncommon and are less than 2% in these series. Transient diarrhoea and hypotension are common after CPN and is seen up to 30% to 40% of the patients, regardless of whether the procedure is being done by the EUS or percutaneous approach. The EUS approach offers several theoretical advantages over the percutaneous option. Most notably is the visualization of the celiac ganglia situated anterior to the aorta, allowing direct injection of the ganglia with alcohol resulting in celiac ganglion neurolysis (CGN). This increases the accuracy of CPN and may result in improved pain control. Furthermore, it could reduce complications associated with the percutaneous approach that includes lower extremity paresthesia and paralysis. Hence, the aim of the study is to compare the efficacy and safety of endoscopic ultrasound (EUS)-guided celiac ganglion neurolysis (CGN) versus percutaneous celiac plexus neurolysis (CPN) in reducing cancer pain in patients suffering from inoperable cancer. With direct visualization and injection of the celiac ganglion, the investigators hypothesis that EUS-guided CGN is more advantageous on improving pain relief and decreasing the need for opioid analgesics in patients with inoperable cancer as compared to percutaneous CPN.

Official Title
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A Randomized Controlled Trial on Endoscopic Ultrasound-guided Celiac Ganglion Neurolysis Versus Percutaneous Celiac Plexus Neurolysis in Patients With Inoperable Cancer

Conditions
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Intractable Abdominal Pain Secondary to Inoperable Malignancy

Intervention / Treatment
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* Procedure: EUS-guided celiac ganglion neurolysis
* Procedure: Percutaneous celiac plexus neurolysis
* Device: Olympus UM 2000
* Device: B-D Quincke Type Point
* Drug: Levobupivacaine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All patients ≥ 18 years old with cytology or histology confirmed pancreatic cancer, or radiologically suggestive of pancreatic cancer ( for patients whom biopsy is impossible) Pain associated with inoperable cancer ( including abdominal pain or back pain, managed according to WHO analgesic ladder, with VAS score ≥4 despite simple analgesics (first 2 steps of WHO analgesic ladder) Inoperability of cancer as demonstrated by EUS, computed tomography (CT) or Positive emission tomography Informed consent available Exclusion Criteria: Unable to safely undergo EUS for any reason Patient is unable to lie prone for procedure Coagulopathy (prolongation of prothrombin time > 18 sec) or thrombocytopenia <80,000 platelets/ml) Previous CPN or other neurolytic block that could affect pancreatic cancer-related pain or had implanted epidural or intrathecal analgesic therapy Another cause for abdominal pain such as pseudocyst, ulcer or other intra-abdominal disorder Allergy to local anaesthesia, contrast, or alcohol Potential patient noncompliance (refusing to follow schedule of events) Active alcohol or other drug use or significant psychiatric illness Expected survival less than 6 weeks

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: EUS-guided celiac ganglion neurolysis<br>Endoscopic ultrasound guided celiac ganglion neurolysis would be performed | Procedure: EUS-guided celiac ganglion neurolysis<br>* EUS-CGN would be performed with a linear video echoendoscope (Olympus UM 2000; Olympus Co Ltd, Japan). The celiac ganglia are visualized under linear EUS and the injection would be applied directly into the ganglia. It is represented by small 2 to 3 mm hypoechoic nodules with hyperechoic foci in the center or a single elongated hypoechoic structure. IIf the ganglia are not identified by EUS, then injection would be performed as bilateral injections at the celiac vessel trunk. All procedures would be performed by a two experienced endosonographer.<br>Device: Olympus UM 2000<br> <br> |
| Active Comparator: Percutaneous celiac plexus neurolysis<br>Percutaneous celiac plexus neurolysis would be performed | Procedure: Percutaneous celiac plexus neurolysis<br>* Percutaneous fluoroscopy-guided CPN would be performed in the operation theatre with the transcural technique. A 22-gauge, 17 cm-long spinal needle (B-D Quincke Type Point, Becton Dickinson &Co., NJ 07417, USA) would be inserted and advanced just caudal to the margin of 12th rib and cephalad to the transverse process of L1 toward the anterolateral surface of the L1 vertebral body. Final needle position would be confirmed by radiographic contrast, layering over anterior surface of aorta. 10mL of levobupivacaine (0.25%), followed by 10mL of absolute alcohol would be injected on both sides using separate punctures.<br>Device: B-D Quincke Type Point<br> <br> Drug: Levobupivacaine<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pain score measured using the visual analogue scale | Pain scores at 2 weeks after the procedure will be measured using the visual analogue scale | 2 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Opioid requirements (Amounts of opioid medications required at assessment interval) | Amounts of opioid medications required at assessment interval | 2 weeks then monthly for 1 yr or till death | 
| Adverse events | Patients would be monitored for presence of adverse events after CGN or CPN. Transient diarrhea and hypotension are common manifestations of the sympathetic blockade and may be seen in up to 38 and 44 percent of the patients. Severe adverse effects after percutaneous CPN include neurologic complications (l%) such as lower extremity weakness and paresthesia, epidural anesthesia, and lumbar puncture. Non-neurological adverse effects (1%) including pneumothorax, shoulder, chest and pleuritic pain, hiccoughing, and hematuria have also been reported. | 2 weeks, then monthly for 1 yr or till death | 
| Quality of life scores (FACT-Hep Chinese module) | QOL would be assessed using the FACT-Hep Chinese module | 2 week, then monthly for 1 yr or till death | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Celiac plexus neurolysis, Celiac ganglion neurolysis, Pancreatic cancer