Endoscopic ultrasound-guided celiac plexus neurolysis (EUS-CPN) technique and analgesic efficacy in patients with pancreatic cancer: A systematic review and meta-analysis.

BACKGROUND: Endoscopic Ultrasound-guided Celiac Plexus Neurolysis (EUS-CPN) for the treatment of abdominal pain in pancreatic cancer can be administered in three different ways, depending on the site of needle insertion: central injection (CI), bilateral injection (BI) and celiac ganglia neurolysis (CGN). This meta-analysis aimed to (1) estimate the overall efficacy of the EUS-CPN; (2) compare the efficacy of each of the three techniques; and (3) investigate demographic and disease characteristics as potential predictors of treatment response. METHODS: We searched MEDLINE and EMBASE for studies that reported the proportion of treatment responders to EUS-CPN overall, and according to the technique used. We performed a random effects meta-analysis of proportions, and meta-regression was used to estimate the association between technique and clinical characteristics on treatment response. The safety profile was reviewed through narrative synthesis. RESULTS: Overall response rate to EUS-CPN was 68% (95% CI 61%-74%) at week two and 53% (95% CI 45%-62%) at week four. There was no evidence of a significant difference in the response rates between the three techniques. Demographics and disease characteristics were not associated with treatment response. Serious complications have been reported for BI and CGN but not for CI. Moderate to high risk of bias was observed. DISCUSSION: EUS-CPN is a useful adjunct to opioids in the management of pain. There is no evidence of a difference in the efficacy among the three techniques, however, CI is the only one for which serious complications have not been reported. Future research should focus on the appropriate timing of EUS-CPN (early versus on demand) and randomised comparison to establish the comparative efficacy of each technique.

Endoscopic ultrasound-guided celiac plexus block and neurolysis.

Endoscopic ultrasound-guided celiac plexus neurolysis (EUS-CPN) is widely used for reducing pain originating from upper abdominal organs. It is mainly indicated to treat pancreatic cancer pain, but also to relieve pain as a result of chronic pancreatitis. Real-time guidance and color Doppler imaging by EUS made the procedure easier and safer, resulting in greater pain relief. Currently, two techniques are used for EUS-CPN. The classic approach, known as the central technique, involves injection of a neurolytic agent at the base of the celiac axis. In the bilateral technique, the neurolytic agent is injected on both sides of the celiac axis. In addition, EUS-guided direct celiac ganglia neurolysis (EUS-CGN) was introduced recently. Pain relief is achieved by EUS-CPN in 70-80% of patients with pancreatic cancer and in 50-60% of those with chronic pancreatitis. The bilateral technique may be more efficient than the central technique, although the central technique is easier and possibly safer. Moreover, EUS-CGN may provide greater pain relief than conventional EUS-CPN. Procedure-related complications include transient pain exacerbation, transient hypotension, transient diarrhea, and inebriation. Although most complications are not serious, major adverse events such as retroperitoneal bleeding, abscess, and ischemic complications occasionally occur.

Pain in Patients with Pancreatic Cancer: Prevalence, Mechanisms, Management and Future Developments.

Pain affects approximately 80% of patients with pancreatic cancer, with half requiring strong opioid analgesia, namely: morphine-based drugs on step three of the WHO analgesic ladder (as opposed to the weak opioids: codeine and tramadol). The presence of pain is associated with reduced survival. This article reviews the literature regarding pain: prevalence, mechanisms, pharmacological, and endoscopic treatments and identifies areas for research to develop individualized patient pain management pathways. The online literature review was conducted through: PubMed, Clinical Key, Uptodate, and NICE Evidence. There are two principal mechanisms for pain: pancreatic duct obstruction and pancreatic neuropathy which, respectively, activate mechanical and chemical nociceptors. In pancreatic neuropathy, several histological, molecular, and immunological changes occur which correlate with pain including: transient receptor potential cation channel activation and mast cell infiltration. Current pain management is empirical rather etiology-based and is informed by the WHO analgesic ladder for first-line therapies, and then endoscopic ultrasound-guided celiac plexus neurolysis (EUS-CPN) in patients with resistant pain. For EUS-CPN, there is only one clinical trial reporting a benefit, which has limited generalizability. Case series report pancreatic duct stenting gives effective analgesia, but there are no clinical trials. Progress in understanding the mechanisms for pain and when this occurs in the natural history, together with assessing new therapies both pharmacological and endoscopic, will enable individualized care and may improve patients' quality of life and survival.

What are the current and potential future roles for endoscopic ultrasound in the treatment of pancreatic cancer?

Pancreatic adenocarcinoma is the fourth leading cause of cancer-related death in the United States. Due to the aggressive tumor biology and late manifestations of the disease, long-term survival is extremely uncommon and the current 5-year survival rate is 7%. Over the last two decades, endoscopic ultrasound (EUS) has evolved from a diagnostic modality to a minimally invasive therapeutic alternative to radiologic procedures and surgery for pancreatic diseases. EUS-guided celiac plexus intervention is a useful adjunct to conventional analgesia for patients with pancreatic cancer. EUS-guided biliary drainage has emerged as a viable option in patients who have failed endoscopic retrograde cholangiopancreatography. Recently, the use of lumen-apposing metal stent to create gastrojejunal anastomosis under EUS and fluoroscopic guidance in patients with malignant gastric outlet obstruction has been reported. On the other hand, anti-tumor therapies delivered by EUS, such as the injection of anti-tumor agents, brachytherapy and ablations are still in the experimental stage without clear survival benefit. In this article, we provide updates on well-established EUS-guided interventions as well as novel techniques relevant to pancreatic cancer.

Development of a new reagent for endoscopic ultrasound-guided celiac plexus neurolysis and tumor ablation therapy

BACKGROUND: Both endoscopic ultrasound-guided celiac plexus neurolysis (EUS-CPN) and tumor ablation using ethanol are very common procedures, and the utility of these therapies has already been reported in prominent journals. However, their effectiveness appears temporary and insufficient, especially EUS-CPN. We therefore have to consider new reagents for improving the results. The present study examined the best concentration of ethanol and povidone iodine mixed with atelocollagen for more effective therapies. METHODS: The effects of the new reagents were confirmed in three live pigs. At first, we injected three kinds of reagents (including indigo carmine) in three separate areas of para-aortic tissue under EUS guidance in one pig. At more than 4 hours after injection, we checked ethanol injection sites after dissection. In next study, we performed EUS-guided injection of a total of six kinds of reagents (two kinds of ethanol, three kinds of povidone iodine, and control atelocollagen) into the livers of two living pigs. After 2 weeks, we examined tissue damage to the liver in the two pigs. RESULTS: The 75% ethanol (absolute ethanol 3.75 mL + 1% atelocollagen 1.25 mL + a very small amount of indigo carmine) was seen like blue gel, and still remained in the para-aortic tissue. Brownish areas of povidone iodine mixed with 3% atelocollagen exhibited clear, regular borders with greatly reduced infiltration into surrounding tissue compared to others. CONCLUSION: We concluded that 75% ethanol mixed with 1% atelocollagen appears optimal for EUS-CPN. Povidone iodine mixed with 3% atelocollagen may be suitable for small tumor ablation therapy.

A Case of Pancreatic Cancer and Opioid Withdrawal after Endoscopic Ultrasound-guided Celiac Plexus Neurolysis / 대한소화기내시경학회지

Pancreatic cancer is usually unresectable upon diagnosis, and treatment aims to optimize the quality of the patient's life by managing symptoms, and, particularly, by providing adequate pain control. When the pain is refractory to opioids, interventions such as celiac plexus neurolysis (CPN) can be considered. Endoscopic ultrasound (EUS)-guided CPN has been introduced for pancreatic cancer. Reported herein is a case of a 75 year-old man with pancreatic cancer who was treated with opioids due to severe abdominal pain. EUS-guided CPN was performed for pain control, and the opioid administration was discontinued as the pain improved dramatically. However, the patient experienced opioid withdrawal symptoms, including anxiety, insomnia, nausea, and vomiting. Thus, although EUS-guided CPN successfully reduced pain in a patient undergoing such treatment and to whom opioid was administered, opioid administration should not be abruptly discontinued. Rather, the opioid dose should be reduced gradually to avoid drug withdrawal.