Effect of endoscopic ultrasound guided celiac plexus block on the palliation of pain in chronic pancreatitis (EPOCH Trial): study protocol for a randomized multicenter sham-controlled trial {1}.

BACKGROUND: Celiac plexus block has been commonly utilized for the treatment of chronic pancreatitis-associated abdominal pain. Prospective studies suggest efficacy in 30 to 50% of patients, although no randomized sham-controlled trials have been performed. The objective of this study is to assess the effect of endoscopic ultrasound (EUS)-guided celiac plexus block on abdominal pain in patients with documented chronic pancreatitis. METHODS: This is a two-arm randomized sham-controlled trial with blinded evaluators. The study will be conducted at multiple academic sites in the United States who are members of the United States Pancreatic Disease Study Group (USPG). Patients referred for EUS to exclude chronic pancreatitis as a cause of abdominal pain as well as those with established painful chronic pancreatitis undergoing EUS for another indication will be eligible. At the time of EUS with confirmation of chronic pancreatitis by standard EUS diagnostic criteria, patients will be randomized to either celiac plexus block or sham whereby an anesthetic and steroid combination will be injected into the celiac plexus or saline will be injected into the gastric lumen with the same type of needle as used for celiac plexus block, respectively. The main outcome measure will be a 50% reduction in abdominal pain using the Brief Pain Inventory Short Form (BPI-SF) at 1 month post-intervention. A number of secondary outcomes will be measured including visual analog scale (VAS), Comprehensive Pain Assessment Tool Short Form (COMPAT-SF) pain scores, and quality of life using a pancreas-specific validated measure (PANQOLI). DISCUSSION: In this study, the effect of celiac plexus block on abdominal pain in patients with chronic pancreatitis will be compared to a sham intervention. This randomized trial will offer a definitive assessment of the role of celiac plexus block for the treatment of abdominal pain in this setting. TRIAL REGISTRATION {2}: ClinicalTrials.gov NCT06178315. Registered on December 21, 2023.

Efficacy of botulinum toxin injection using the right-sided unilateral retrocrural approach for celiac plexus in a cancer survivor with persistent abdominal pain: a case report.

Cancer survivors often face persistent abdominal pain, necessitating optimal pain management. While celiac plexus block (CPB) and botulinum toxin (BT) injection are viable options, traditional methods may encounter challenges due to patient-specific concerns and anatomical complexities. Here, the case of a cancer survivor in his 70 s experiencing recurrent abdominal pain, who declined conventional percutaneous CPB approaches due to anxiety related to aortic puncture, is presented. Following a pancreaticoduodenectomy, the patient developed chronic abdominal pain attributed to adhesions leading to small bowel obstruction. Concurrently, there was notable psychological distress, including anxiety, depression, and heightened concerns regarding tumor recurrence. Considering the patient's specific concerns, a right-sided unilateral retrocrural single-needle technique was proposed, aimed at alleviating pain, while avoiding conventional CPB approaches. Initial right-sided retrocrural CPB offered short-term relief, prompting a subsequent BT injection using the same approach. Following BT injection, the patient reported significant and sustained pain reduction (from 8 to 1 on an 11-point numerical rating scale) at both 12 and 20 weeks post-procedure. Right-sided retrocrural BT injection offers an alternative approach, addressing patient concerns and demonstrating prolonged pain relief. This may benefit cancer survivors with upper abdominal pain, emphasizing the importance of personalized and innovative pain management strategies.

Celiac plexus radiosurgery for pain management in advanced cancer: a multicentre, single-arm, phase 2 trial.

BACKGROUND: Refractory upper abdominal pain or lower back pain (retroperitoneal pain syndrome) related to celiac plexus involvement characterises pancreatic and other upper gastrointestinal malignancies and is an unmet need. We hypothesised that ablative radiation delivered to the celiac plexus would decrease pain. METHODS: This multicentre, single-arm, phase 2 study was done at eight hospitals in five countries (Israel, Poland, Canada, the USA, and Portugal). Eligible patients aged 18 years or older with an average pain level of 5-10 on the Brief Pain Inventory short form (BPI-SF), an Eastern Cooperative Oncology Group performance status score of 0-2, and either pancreatic cancer or other tumours involving the celiac axis, received a single fraction of 25 Gy of external-beam photons to the celiac plexus. The primary endpoint was complete or partial pain response based on a reduction of the BPI-SF average pain score of 2 points or more from baseline to 3 weeks after treatment. All evaluable patients with stable pain scores were included in response assessment. The trial is registered with ClinicalTrials.gov, NCT03323489, and is complete. FINDINGS: Between Jan 3, 2018, and Dec 28, 2021, 125 patients were treated, 90 of whom were evaluable. Patients were followed up until death. Median age was 65·5 years (IQR 58·3-71·8), 50 (56%) were female and 40 (44%) were male, 83 (92%) had pancreatic cancer, and 77 (86%) had metastatic disease. Median baseline BPI-SF average pain score was 6 (IQR 5-7). Of the 90 evaluable patients at 3 weeks, 48 (53%; 95% CI 42-64) had at least a partial pain response. The most common grade 3-4 adverse events, irrespective of attribution, were abdominal pain (35 [28%] of 125) and fatigue (23 [18%]). 11 serious adverse events of grade 3 or worse were recorded. Two grade 3 serious adverse events were probably attributed to treatment by the local investigators (abdominal pain [n=1] and nausea [n=1]), and nine were possibly attributed to treatment (seven were grade 3: blood bilirubin increased [n=1], duodenal haemorrhage [n=2], abdominal pain [n=2], and progressive disease [n=2]; and two were grade 5: gastrointestinal bleed from suspected varices 24 days after treatment [n=1] and progressive disease [advanced pancreatic cancer] 89 days after treatment [n=1]). INTERPRETATION: Celiac plexus radiosurgery could potentially be a non-invasive palliative option for patients with retroperitoneal pain syndrome. Further investigation by means of a randomised comparison with conventional celiac block or neurolysis is warranted. FUNDING: Gateway for Cancer Research and the Israel Cancer Association.

Endoscopic Management of Pain due to Chronic Pancreatitis.

Pain secondary to chronic pancreatitis is a poorly understood and complex phenomenon. Current endoscopic treatments target pancreatic duct decompression secondary to strictures, stones, or inflammatory and neoplastic masses. When there is refractory pain and other treatments have been unsuccessful, one can consider an endoscopic ultrasound-guided celiac plexus block. Data on the latter are underwhelming.

Retroperitoneal fasciae as barriers for nerve and arterial passages connecting the retroperitoneal region to the peritoneal organs.

The fascia of the pancreatic head is referred to as the retropancreatic fascia of Treitz, and that of the body and tail of the pancreas is named the retropancreatic fascia of Toldt. However, the spatial relationship between the nerves, fascia, and the distribution of the fascia on the dorsal side of the pancreas remains unclear. Therefore, this study aimed to explore the distribution of these fasciae and elucidate the spatial relationship between the nerves and arteries connecting the retroperitoneal space and the peritoneal organs by studying eight cadavers using macroscopic anatomical examination, wide-range serial sectioning, and three-dimensional reconstruction. The fasciae of Treitz and Toldt converge caudally to the root of the superior mesenteric artery (SMA), forming a narrower gap around the roots of the celiac trunk and SMA than in the celiac plexus. The fasciae eventually get closer to each other, and the boundary between them becomes obscured, providing coverage to the anterior surface of the aorta between the SMA and the inferior mesenteric artery. The celiac plexus does not penetrate the fascia but converges before spreading into the pancreas. Similarly, the arteries pass through this gap in the fasciae. Our findings suggest that the retroperitoneal space and peritoneal organs are connected through a narrow no-fascia area, with the distribution of the fascia relating to nervous and vascular pathways. Our findings reveal that the distribution of the avascular plane may provide a crucial anatomical foundation for abdominal digestive organ surgery by reducing bleeding volume and determining the dissection region.

Efficacy and Safety of Celiac Plexus Neurolysis Versus Splanchnic Nerve Neurolysis in the Management of Abdominal Cancer Pain: A Meta-analysis of 359 Patients.

BACKGROUND: Splanchnic nerve neurolysis (SNN) is commonly used as an alternative pain control technique to celiac plexus neurolysis (CPN) in patients with distortion of anatomy, but the analgesic effect and relative risks of the 2 procedures remain controversial in general condition. OBJECTIVES: The aim of this study was to evaluate the pain condition, safety, and symptom burden of SNN compared with CPN. STUDY DESIGN: A systematic review and meta-analysis of neurolysis therapy for intractable cancer-related abdominal pain. METHODS: A systematic search was performed for randomized controlled trials comparing SNN and CPN using the PubMed, Medline, Cochrane Library, Web of Science, Google Scholar, and China National Knowledge Infrastructure databases. Meta-analysis was performed using Stata Version 15.0. Outcomes included pain condition, opioid consumption, adverse effects, quality of life (QOL), and survival rate. Standardized mean difference (SMD) was calculated for continuous outcomes with its corresponding 95% CI. LIMITATIONS: Study limitations include challenges to make subgroup analysis by intervention measures and addressing inevitable heterogeneity. Larger studies are needed for survival rates and further insights. RESULTS: Seven studies involving 359 patients were included. No significant difference was found in pain condition at 2 weeks [SMD = 0.75, 95% CI (-0.25, 1.74), P > 0.05], 2 months [SMD = 1.10, 95% CI (-0.21, 2.40), P > 0.05] and 6 months [SMD = 0.53, 95% CI (-0.02, 1.08), P > 0.05] between SNN and CPN. Opioid consumption was comparable at 2 weeks [SMD = 0.57, 95% CI (-1.21, 2.34), P > 0.05] and one month [SMD = 0.37, 95% CI (-1.33, 2.07), P > 0.05]. However, SNN was associated with a statistically significant reduction in the opioid consumption at 2 months postoperatively [SMD = 0.99, 95% CI (0.68, 1.30), P < 0.05]. A systematic review was performed for adverse effects and QOL. CONCLUSIONS: Our evidence supports that the analgesic effect of SNN is equivalent to that of CPN, independent of changes in the anatomical structure of the abdominal nerve plexus. SNN requires less use of opioids at 2 months and does not show greater improvement in pain burden compared to CPN.

Clinical Outcomes after Median Arcuate Ligament Release in Patients Responsive to Celiac Plexus Block.

PURPOSE: To determine if symptom relief with celiac plexus block (CPB) is associated with favorable clinical outcomes after median arcuate ligament release (MALR) surgery. MATERIALS AND METHODS: A retrospective review was performed from January 2000 to December 2021. Fifty-seven patients (42 women, 15 men; mean age, 43 years [range, 18-84 years]) with clinical and radiographic features suggestive of median arcuate ligament syndrome (MALS) underwent computed tomography (CT)-guided percutaneous CPB for suspected MALS. Clinical outcomes of CPB and MALR surgery were correlated. Adverse events were classified according to the Society of Interventional Radiology (SIR) guidelines. RESULTS: CT-guided percutaneous CPB was successfully performed in all 57 (100%) patients with suspected MALS. A cohort of 38 (67%) patients showed clinical improvement with CPB. A subset of 28 (74%) patients in this group subsequently underwent open MALR surgery; 27 (96%) responders to CPB showed favorable clinical outcomes with surgery. There was 1 (4%) CPB-related mild adverse event. There were no moderate, severe, or life-threatening adverse events. CONCLUSIONS: Patients who responded to CPB were selected to undergo surgery, and 96% of them improved after surgery.

Topical Diclofenac to Manage Opioid-Refractory Pain in a Rare Pancreatic Fibrosarcoma.

Pancreatic cancer is often diagnosed at an advanced stage and is frequently associated with severe pain. Traditional pain management in this condition may be improved with the use of topical diclofenac. A 39-year-old man with advanced pancreatic fibrosarcoma metastatic to the thoracic spine presented to the hospital with severe abdominal pain refractory to escalating doses of opioids. A celiac plexus block produced significant, yet inadequate, pain reduction. Satisfactory pain control and opioid de-escalation were ultimately achieved with the application of topical diclofenac gel to an area of bony metastasis. This case illustrates the potential for pain control using topical diclofenac in patients with pancreatic soft tissue tumors and vertebral metastases. Topical diclofenac may exert antitumoral effects and targeted application may improve absorption, leading to improved pain control. The use of topical diclofenac for pain management in metastatic pancreatic cancer presents an interesting tool that should be considered in similar cases.

Endoscopic Ultrasound-Guided Pain Management.

The diagnosis and management of pancreatic cancer has become a standard role for the endoscopic oncologist. Pancreatic cancer can produce disabling abdominal pain, and the medical management of this pain is often challenging. Endoscopic ultrasound-guided celiac plexus neurolysis and celiac ganglia neurolysis serve as an alternative or adjunct for pain control in these patients. There remains a great deal of practice variability with regard to techniques and approaches. This article summarizes the latest scientific evidence and highlights contemporary best practice advice for these procedures.

Protocol for a randomized controlled trial of endoscopic ultrasound guided celiac plexus neurolysis (EUS-CPN) with vs without bupivacaine.

BACKGROUND: Pancreatic cancer is a devastating disease with less than 5% 5-year survival. Inoperable patients often present with pain. Randomized controlled trial have shown that endoscopic ultrasound-guided celiac plexus neurolysis (EUS-CPN) improves pain control. It is usually performed by injecting bupivacaine followed by absolute alcohol around the celiac axis. STUDY DESIGN: Single center, randomized, double blind controlled trial of EUS-CPN with and without bupivacaine in patients with inoperable malignancy (pancreatic or other) involving the celiac plexus. The study was approved by research ethics board with approval number of 2022-9969, 21.151 and registered on ClinicalTrials.gov (NCT04951804). DISCUSSION: We hypothesize that bupivacaine is superfluous and may actually reduce pain control by diluting the neurolytic effect of alcohol. Bupivacaine is also potentially dangerous in that it may produce serious adverse events such as arrythmias and cardiac arrest if inadvertently injected intravascularly. CONCLUSION: This randomized trial is designed to assess whether bupivacaine is of any value during EUS-CPN.

Celiac plexus block combined with 125I seeds for refractory epigastric pain from abdominal malignancies: a retrospective case-control study.

PURPOSE: To evaluate the clinical efficacy of celiac plexus block (CPB) combined with 125I seeds implantation (ISI) for refractory epigastric pain from abdominal malignancies. METHODS: The data of 81 patients with refractory epigastric pain [visual analog scale (VAS) score ≥ 4] from abdominal malignancies were collected in this retrospective case-control study. Group A (n = 40) was treated with CPB alone, while Group B (n = 41) underwent CPB combined with ISI. The primary study endpoints were the VAS score, quality of life (QoL), and local tumor control (LTC) rate. The secondary endpoints were complications, progression-free survival (PFS), and overall survival (OS). RESULTS: The VAS scores at week 2 (T2), week 4 (T4), week 8 (T8), and week 12 (T12) in both groups were significantly lower compared with the pretreatment values (all P < 0.01). VAS scores in Group B showed a sustained decrease, especially for "mild pain" and "moderate pain," while the VAS scores in Group A rebounded at T8 and T12 (both P < 0.01). The QoL in Group B improved significantly from T4 until T12, which better than that at T12 in Group A (all P < 0.01). The LTC rates at T8 were 35.0% and 92.7% in Groups A and B, respectively, with a significant difference (P < 0.01). Group B had a slightly lower complication rate and a slightly longer median PFS/OS than group A, but neither was statistically different (P = 0.09 and P = 0.99, respectively). CONCLUSION: CPB combined with ISI performs more sustained pain relief (up to 12 weeks) compared to CPB alone, and ultimately improves the patients' QoL.

Role of Intraoperative Coeliac Plexus Neurolysis on Postoperative Pain Management for Chronic Pancreatitis.

Control of pain in patients with chronic pancreatitis is difficult because 30.0% to 50.0% of patients still experience persistence or recurrence of pain even after surgery. So a combined approach of surgery and coeliac plexus neurolysis was carried out in this study to see the relief of pain and reduce the requirement of analgesics in these patients. This prospective observational comparative study was carried out in the Department of Hepatobiliary, Pancreatic and Liver Transplant Surgery in Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh from November 2017 to October 2018. Forty one (41) study participants with the diagnosis of chronic pancreatitis were included consecutively in this study. The participants were divided into two groups. Group I (n=18) underwent pancreatic surgery with coeliac plexus neurolysis by infiltration of 20ml of 100% alcohol in the loose areolar tissue 10ml each into right and left para-aortic space at the level of coeliac trunk and Group II (n=23) underwent pancreatic surgery only. Participants' preoperative data were collected from patient record file. Number, frequency and intensity of pain and requirement of amount of analgesics for the last 3 months were recorded from patients' history. The intensity of pain was categorized by visual analog scale (VAS) preoperatively. The participants of both groups were followed up at 1, 2 and 3 months interval and asked for disappearance or reduction of pain, frequency of attack and requirement of analgesics. Again visual analog scale was used for categorization of pain. Pain free period was recorded after the end of follow up period. Pain reduction occurred after surgery in both groups. But when pain relief was compared on the basis of VAS (Visual Analogue Scale), it was significantly better in Group I after 1 month of surgery than Group II (p=0.05). But 2 and 3 months after surgery this difference became insignificant (p=0.246 and 0.264). No statistical difference was found in terms of analgesic usage, severe acute attack or hospital admission (p=0.511, 0.439 and 0.495) at the end of 3 months follow up. Participants in Group I had significantly longer pain free period than Group II (p=0.025). Regarding complications, postural hypotension developed in 5.6% (1) patients. Diarrhea developed in 11.1% (2) patients in Group I and wound infection developed in 2 patients in each groups respectively. No patients developed any major complications like anastomotic leakage, deep or organ or space infection. Intraoperative coeliac plexus neurolysis reduces pain immediately after surgery and provides longer pain free period in patients with chronic pancreatitis after surgery.

Nursing Cooperation Pattern for Patients With Advanced Pancreatic Cancer and Abdominal Pain Undergoing Endoscopic Ultrasound-guided Celiac Plexus Neurolysis.

Context: Patients with pancreatic cancer (PC) at a late stage often suffer from severe abdominal pain due to the invasion of celiac plexus, and the analgesics they receive often have intolerable side effects. Endoscopic, ultrasound-guided, celiac plexus neurolysis (EUS-guided CPN) can have a good therapeutic effect. Objective: The study intended to evaluate the ability of two nursing cooperation patterns to reduce patients' pain, decrease operation times, increase operational efficiency, and increase nurses' satisfaction, for patients with advanced PC and abdominal pain who received EUS-guided CPN. Design: The research team designed a retrospective controlled study. Setting: The study took place at the Shenzhen People's Hospital of the Second Clinical Medical College of Jinan University in Shenzhen, China, and at the Changhai Hospital of the Second Military Medical University in Shanghai, China. Participants: Participants were 40 patients with advanced PC who received EUS-guided CPN at one of the two hospitals between January 2019 and January 2020. Intervention: Twenty participants at Changhai Hospital received the traditional nursing cooperation pattern and became the control group, and 20 participants at the Shenzhen People's Hospital received the new nursing cooperation pattern and became the intervention group. Outcome Measures: The study measured clinical data, nursing measures, diagnostic significance, and key points for the two patterns as well as compared the effects of the new nursing cooperation method to that of traditional nursing. If the measurement data met the requirements for normality, the team used the two independent sample t-test for the intergroup comparisons. If normality wasn't satisfied, the team used medians and interquartile ranges (IQRs) for expression and the rank sum test for the intergroup comparisons. Counting data were expressed using the constituent ratio, and team used the chi-square test for comparisons between groups. P < .05 was considered to be statistically significant. Results: The operations were successful, and no complications occurred. No significant difference existed in the pain scores between the control group and the intervention group (P > .05), while a significant difference occurred in the nurses' operation times and satisfaction. Not only were the scores for operation times for the control group (97) and the intervention group (59) significantly different, but also the nurses' satisfaction was significantly higher for the intervention group postintervention, at 83.35 ± 5.25, than for the control group, at 62.25 ± 8.18 (P < .001). Such a new nursing cooperation method could assist in patient's rehabilitation and increase nurses' satisfaction. Conclusions: The new nursing cooperation method for patients with advanced PC and abdominal pain undergoing EUS-guided CPN can reduce operation time and improve nurses' satisfaction.

Percutaneous retrocrural versus ultrasound-guided coeliac plexus neurolysis for refractory pancreatic cancer pain.

We report a successful case of fluoroscopic percutaneous retrocrural coeliac plexus neurolysis (PRCPN) for pancreatic cancer pain refractory to endoscopic ultrasound-guided coeliac plexus neurolysis (EUS-CPN). A 55-year-old man with upper abdominal pain due to end-stage pancreatic cancer underwent EUS-CPN. Although CT revealed distribution of the contrast medium with neurolytic agent around the left and cephalic sides of the coeliac artery, the pain did not improve and became even more severe. PRCPN was performed, resulting in the drastic improvement of pain immediately. PRCPN should be considered when EUS-CPN is not effective.

Endoscopic ultrasound-guided celiac plexus neurolysis in pancreatic cancer-associated pain: different technical approaches in three challenging cases.

Abdominal pain is severe in the vast majority of patients with pancreatic cancer. In some cases, chronic use of analgesics markedly reduces quality of life due to side effects. Endoscopic ultrasound-guided celiac plexus neurolysis is a procedure that controls cancer-associated pain in this population and consists of injecting a neurolytic agent around or within the celiac plexus. In this report, we present three cases with different technical approaches for celiac plexus neurolysis.

EUS-guided celiac plexus neurolysis for pancreas cancer - Finally established or still under review?

Patients with pancreas cancer must deal frequently with intractable and refractory pain. Endoscopic ultrasound guided-celiac plexus neurolysis (EUS-CPN) has been the most studied and used therapeutic technique aimed to destroy the pain fibres that allow the pancreas to communicate with the central nervous system. A neurolytic agent, most commonly ethanol, is optimally spread around the celiac axis in order to reduce pain and mitigate narcotic requirements. This can be performed early to prevent the spiral of pain and medication use, or more historically as salvage therapy. Different techniques to best administer the ethanol for effective EUS-CPN are still being debated. New EUS-guided injection techniques with radiofrequency, radioactive, and/or chemotherapeutic agents need more study.