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Interventional endoscopic ultrasonography (EUS) has been developed mainly for the treatment of pancreaticobiliary disorders (e.g. cyst drainage for pancreatic pseudocysts, biliary drainage for malignant biliary obstruction, and celiac plexus neurolysis). Recently, the application of interventional EUS has been expanded to a new field, the treatment of gastrointestinal varices. There have been several studies examining this new technique for the treatment of esophageal and gastric varices. In the present review, we have summarized the current status of interventional EUS for the treatment of esophageal and gastric varices (e.g. EUS-guided coil deployment for gastric varices) and clarified the clinical feasibility of this procedure.

Background & Aims Endoscopic ultrasound (EUS) allows visualization of celiac lymph nodes (CLNs) and celiac ganglia (CG). Reliably distinguishing these structures is important for tumor staging and CG ablative therapies. We aimed to evaluate the accuracy of EUS in distinguishing CLNs from CG using a strict cytopathology reference standard. We also determined the rate of detection of CLN and CG by conventional cross-sectional imaging. Methods From EUS and cytopathology databases, we identified all patients who underwent EUS-FNA of a presumed CLN or CG from October 1, 2004, through March 1, 2017, and compared the findings with those from cytology (reference standard). Indeterminate cytology results were re-reviewed. EUS imaging (ie, index test) results were compared with those from the reference standard. An expert radiologist re-reviewed computed tomography and magnetic resonance images from 100 lesions, from 94 randomly selected patients with a reference standard, to determine the rates of CLN and CG detection. Results A total of 504 patients (mean age, 63.4 ± 13.2 years; 292 men) underwent a median of 7 EUS-FNA passes (range, 1–13) for a total of 566 lesions perceived to be either a CLN or CG; the cytology reference standard was available for 521 lesions (92.1%). When we excluded indeterminate cytology results, the EUS accurately identified 281/286 CLNs (98.3%) and 166/186 CGs (89.2%), for an overall accuracy of 447/472 (94.7%). EUS-FNA distinguished CG from CLNs with a 93.3% sensitivity, 93.7% specificity, a positive predictive value of 96.2%, and a negative predictive value of 89.2%. Of 100 lesions in 94 patients randomly selected for a second expert radiology review, computed tomography and magnetic resonance imaging detected 59/67 CLNs (88.1%) and 13/33 CG (39.4%). Conclusion EUS accurately distinguishes CLNs from CG. EUS might therefore be used to increase the accuracy of tumor staging, to select tumor stage-appropriate therapy, and to guide CG-ablative therapies.

Endoscopic ultrasound (EUS) is a remarkable tool with multiple applications. Since its introduction approximately 30 years ago, it has become a pivotal modality for numerous indications such as the evaluation of pancreatobiliary pathologies, staging of luminal gastrointestinal cancers, assessment of subepithelial lesions, and for tissue acquisition [1, 2]. During the past few years, EUS has shifted from a purely diagnostic tool to a more interventional procedure. For example, it can now be used to drain fluid collections, to provide biliary access and decompression, to perform celiac plexus neurolysis, and to deposit fiducial markers.

Abdominal pain is an important symptom in most patients with pancreatic ductal adenocarcinoma (PDAC). Adequate control of pain is often unsatisfactory due to limited treatment options and significant variation in local practice, emphasizing the need for a multidisciplinary approach. This review contends that improvement in the management of PDAC pain will result from a synthesis of best practice and evidence around the world in a multidisciplinary way. To improve clinical utility and evaluation, the evidence was rated according to the GRADE guidelines by a group of international experts. An algorithm is presented, which brings together all currently available treatment options. Pain is best treated early on with analgesics with most patients requiring opioids, but neurolytic procedures are often required later in the disease course. Celiac plexus neurolysis offers medium term relief in a substantial number of patients, but other procedures such as splanchnicectomy are also available. Palliative chemotherapy also provides pain relief as a collateral benefit. It is stressed that the assessment of pain must take into account the broader context of other physical and psychological symptoms. Adjunctive treatments for pain, depression and anxiety as well as radiotherapy, endoscopic therapy and neuromodulation may be required in selected patients. There are few comparative studies to help define which combination and order of these treatment options should be applied. New pain therapies are emerging and could for example target neural transmitters. However, until better methods are available, management of pain should be individualized in a multidisciplinary setting to ensure optimal care., SCOPUS: re.j, info:eu-repo/semantics/published

Celiac plexus neurolysis (CPN) has become a minimally invasive approach for the management of patients with unresectable pancreatic cancer and abdominal pain unresponsive to medical treatment. CPN has been shown to have long-lasting improvement in abdominal pain and decreased narcotic usage in 70% to 90% of patients. Therefore, the aim of this paper was to report our experience with CPN in the treatment of two cases of advanced pancreatic cancer, with satisfying results in controlling pain. The use of CT scan-guided CPN should be considered and performed relatively early in the course of disease to offer optimal pain relief and increase the patient’s quality of life.

For patients with pain from upper abdominal malignancies, celiac plexus neurolysis can provide an effective means of pain control. However, there are instances when traditionally described percutaneous approaches may not be technically feasible. We describe here the successful use of a novel single-needle retroaortic approach as an alternative approach to celiac plexus neurolysis.We present 4 cases of patients with pain from upper abdominal malignancies in whom we performed celiac plexus neurolysis using a novel single-needle retroaortic approach. All 4 patients had significant pain relief and no significant adverse effects from the retroaortic approach.

Chronic upper abdominal pain occurs as a complication of various malignant and benign diseases including pancreatic cancer and chronic pancreatitis, and when present may contribute to lower quality of life and higher mortality. Though various pain management strategies are available as part of a multimodal approach, they are often incompletely effective and accompanied by side effects. Pain originating in upper abdominal viscera is transmitted through the celiac plexus, which is an autonomic plexus located in the retroperitoneum at the root of the celiac trunk. Direct intervention at the level of the plexus, referred to as celiac plexus block or neurolysis depending on the injectate, is a minimally invasive therapeutic strategy which has been demonstrated to decrease pain, improve function, and reduce opiate dependence. Various percutaneous techniques have been reported, but, with appropriate preprocedural planning, use of image guidance (usually computed tomography), and postprocedural care, the frequency and severity of complications is low and the success rate high regardless of approach. The main benefit of the intervention may be in reduced opiate dependence and opiate-associated side effects, which in turn improves quality of life. Celiac plexus block and neurolysis are safe and effective treatments for chronic upper abdominal pain and should be considered early in patients experiencing such symptoms.

EUS-guided celiac plexus neurolysis (EUS–CPN) can be performed for alleviating pain originating from the upper abdominal organs and, particularly, when the primary indication for pain is pancreatic cancer pain. Two different techniques are currently used when applying EUS–CPN. The classic approach, known as the central technique, involves injection of a neurolytic agent at the base of the celiac axis, and the second approach, the bilateral technique, involves injection of the neurolytic agent on both sides of the celiac axis. Moreover, it was recently established that celiac ganglia can be examined and visualized by EUS. Therefore, EUS-guided direct celiac ganglia neurolysis (EUS–CGN) has been introduced as a new promising method. These techniques are performed with real-time imaging and with Doppler assessment of the interposing vessels. Therefore, they are more accurate, safe, and convenient than other classic approaches such as radiographic, fluoroscopic, or CT guidance. The effective rates reportedly vary from 50 to 90%. Common complications included transient diarrhea, transient pain exacerbation, transient hypotension, and inebriation, but they are not serious.

Background Endoscopic ultrasound (EUS) has been used in the clinical arena for almost 35 years and it is now well-integrated in everyday hospital practice. Method We conducted a systematic review of the available English-language articles. Objective The purpose of this review is to summarize the relevant applications of operative EUS. Results More than 5000 scientific papers published in the literature have demonstrated its high accuracy for the diagnosis and staging of a variety of benign and malignant conditions. The main indications of operative EUS, both diagnostic and therapeutic, are related to its ability to combine ultrasound imaging and safe and effective needle insertion into lesions originating from the gut wall and from organs nearby. In addition, technologic advancements of echoendoscopes with a therapeutic working-channel have allowed to perform several EUS-guided interventions, i.e. celiac plexus neurolysis, drainage of fluid collections, drainage of dilated biliary and pancreatic ducts, and vascular interventions.

An interventional procedure like celiac plexus neurolysis (CPN) has a significant role in relieving intractable pain in patients with locally advanced abdominal malignancies. Ultrasound (USG) guidance enables performance of bedside CPN by real-time visualization of the needle trajectory. The objective of the study was to perform percutaneous USG-guided CPN and to verify technical outcomes of the procedure using a post-procedure CT scan. Eleven eligible patients of advanced upper abdominal malignancies having a pain score of >3/10 on visual analog scale (VAS) were recruited to undergo CPN. A post-procedure CT scan was performed to evaluate technical outcomes of the procedure. Patients were evaluated for pain relief. They were followed up at the 1st, 4th, and 6th weeks after CPN. Eleven patients underwent USG-guided CPN. The injected drug was visualized as an echogenic cloud in ultrasound in 7 out of 11 (64%) patients. In the remaining 4 patients, the echogenic cloud was not well formed. In the post-procedure CT scan, the spread of the drug was seen in all 11 patients. This spread was bilaterally symmetrical in 7 (64%) patients and asymmetrical or unilateral in 4 (36%) patients. All patients in the immediate post-procedure period and 91% of the patients during the 1st-, 4th-, and 6th-week follow up had improvement in their pain scores. A post-procedure CT scan was useful in verifying the technical outcome of USG-guided CPN in patients with advanced upper abdominal malignancies.

Pancreatic adenocarcinoma is currently the fourth-leading cause of cancer-related death. Up to 60–90% of patients with advanced disease suffer cancer-related pain, severely impacting their quality of life. Current management involves primarily pharmacotherapy with opioid narcotics and celiac plexus neurolysis; unfortunately, both approaches offer transient relief and cause undesired side-effects. High intensity focused ultrasound (HIFU) is a non-invasive thermal ablation technique that has been used to treat pancreatic cancer. This meta-analysis aims to evaluate the role of HIFU in pain palliation of advanced unresectable pancreatic adenocarcinoma. An electronic search was performed in PubMed Medline database up to the end of July 2016, for unresectable pancreatic cancer pain palliation with HIFU. Pertinent studies were identified through the PubMed search engine using the following keywords: HIFU, pancreas, pancreatic cancer, pain and palliation. Additional studies were included after manual search of the selected bibliographies. Pain palliation results reported in each study were analyzed using a logit-transformed random-effects model using the inverse variance method, with the DerSimonian-Laird estimator for τ 2, and Cochran’s Q test for heterogeneity among studies. The I2 was calculated to assess the percentage of the total variability in the different effect size estimates that can be attributed to heterogeneity among the true effects. A rank correlation test of funnel plot asymmetry was done to assess possible publication bias. The meta-analysis includes a total number of 23 studies with 865 patients, 729 with pancreatic cancer. The population enrolled ranges from 3 patients in the smallest series, up to 61 in the largest study. τ 2 (variance among studies) was 0.195, and I2 (percentage of variation among studies) was 40% (95% CI: 1–64%); the Q test p-value was 0.026, indicating significant heterogeneity among studies. Among 639 patients treated with HIFU, 567 complained of pancreatic pain before the treatment and 459 patients experienced partial or complete pain relief after treatment. The random effects estimate of the proportion of patients with pain reduction was 0.81 (95% CI: 0.76–86). HIFU appears to be an effective tool for pain palliation in advanced pancreatic cancer. Studies assessing treatment in patients with pancreatic adenocarcinoma are limited by factors such as small sample sizes and heterogeneity in clinical definitions and assessments. Prospective randomized and standardized studies are necessary to confirm the effectiveness of HIFU in relieving pain, and to evaluate for any potential impact on tumor control and patient survival.

Background: Abdominal pain from primary cancer or metastatic disease is a significant cause of pain for patients undergoing treatment for the disease. Patient's pain may be resistant or non-responsive to the pharmacological management, hence minimal invasive pain intervention like celiac plexus neurolysis or splanchnic nerve rhizolysis may be required to relieve pain of such patients. Objective: The aim of this retrospective study is to assess the effect of celiac plexus neurolysis for pain relief in patients with upper gastro-intestinal malignancies. Study Design: This is a retrospective, observational study with short review. Methods: This retrospective observational study was done in the Pain Medicine unit from 2016 and November 2018. Ninety-four patients with upper abdominal malignancy and unrelenting pain, non-responsive or poorly responsive to pharmacological treatment as per WHO ladder of analgesics, received fluoroscopy-guided celiac plexus neurolysis (CPN). All the patients underwent celiac plexus neurolysis through Trans-Aortic approach and the primary outcome measure was pain as assessed with Visual Analogue Scale (VAS) ranging from 0 to 10; the secondary outcome measures were morphine consumption per day (M), quality of life (QOL) as assessed by comparing the percent of positive responses and complications, if any. These were noted and analyzed prior to intervention and then on day 1, and months 1, 2, 3, 4, 5, 6 following CPN. Results: Follow up was completed 6 months after the procedure. VAS score, daily morphine consumption, and the quality of life showed improvement for the duration of the study. There was some relapse in pain and deterioration in QOL during the fourth to sixth month of pain intervention due to disease progression. Some transient known side effects also occurred. Conclusion: Trans-Aortic celiac plexus neurolysis with low volume of alcohol is a safe procedure providing up to 6 months of pain relief and is an effective, well established, minimally invasive procedure for abdominal pain due to primary malignancy or metastatic spread.

Background and Objectives: Increasing evidence suggests a prognostic role of sarcopenia in pancreatic cancer patients. The aim of this study was to assess the influence of sarcopenia on treatment outcomes after EUS-guided celiac plexus neurolysis (CPN). Materials and Methods: Data regarding 215 patients treated with EUS CPN between 2004 and 2019 were reviewed. Determination of body composition was conducted on contrast-enhanced CT scan, and pain response was considered as the primary outcome. Univariate and multivariate logistic regression was performed to identify the independent predictors of pain response. Results: Treatment was successful in 187 patients (86.9%). The median age was 62 (range 39–84) years, and most patients were male (61.8%). Of the whole study population, 139 patients (64.6%) were defined as sarcopenic, of which 116 (83.4%) responded to the treatment and 5 (3.5%) experienced a complete response. Among 76 nonsarcopenic participants, 71 (93.4%) responded to the treatment and 22 (28.9%) obtained a complete response (P = 0.03 and

33 patients [13 female] with metastatic intractable upper Abdominal Cancer Pain were treated with celiac plexus neurolytic block with 60% alcohol. Aim of study is to observe the effectiveness of three different techniques of celiac plexus block, unilateral paravertibral, bilateral paravertibral and Paravertibral transaortic approach of celiac plexus blocks under C- arm guidance. Satisfactory pain relief occurs in all three techniques but out- come of transaortic approach a little better than other methods. Pain intensity was assessed by VRS and VAS Scale. Celiac plexus blocks are a suitable technique for upper abdominal visceral metastatic pain. Its effects are prolonged and also increase bowel movement, improve appetite and reduced morphine consumption. This is an initial study and numbers of subject are few. So more study required to get conclusive result. Skilled manpower and appropriate case selection is mandatory for successful results. DOI: http://dx.doi.org/10.3329/bmj.v41i2.18800 Bangladesh Medical Journal 2012 Vol. 41 No. 2: 23-26

Pancreatic cancer is a highly lethal disease with a dismal prognosis. It will probably become the second leading cause of cancer-related death within the next decade in Western countries. Over 80% of patients undergo palliative treatment for unresectable pancreatic cancer due to locally advanced disease or metastases. Those patients often develop gastric outlet obstruction (GOO), obstructive jaundice and pain during the course of their disease. Symptoms such as vomiting, anorexia, pruritus and jaundice will impact the quality of life (QOL) and could delay the administration of the chemotherapy. Palliative therapy in pancreatic cancer aims to relieve the symptoms durably and to improve the QOL. Palliative surgery was traditionally considered as a gold standard with the “double by-pass” including biliary-digestive and gastro-jejunal anastomosis. However, since the development of endoscopic stenting and minimally invasive surgery, the choice of the best modalities remains debated. While there is still a place for surgical gastrojejunostomy (GJ) in case of duodenal or GOO, endoscopic biliary stenting during endoscopic retrograde cholangiopancreatography (ERCP) is now accepted as the gold standard in case of obstructive jaundice. In pain management, endoscopic ultrasound guided or percutaneous celiac plexus neurolysis is recommended. The selection of the best technique should consider the effectiveness and the morbidity of the treatment, the performance status of the patient and the disease stage. While endoscopic stenting is associated with earlier recovery and shorter length of stay, recurrence of symptoms and reintervention are less frequent after palliative surgery. Finally, controversy exists on whether to perform prophylactic palliative surgery in the absence of symptoms when unresectable disease is discovered during surgical exploration.

Celiac plexus block is a time tested method for management of pain. It is conventionally done via posterior approach. We report successful use of anterior celiac plexus to manage pain in a case of chronic pancreatitis with necrotising fasciitis of the back.

A 28-weeks gestation pregnant patient with chronic pacreatitis and severe abdominal pain leading to impaired nutrition is presented. After detailed consideration of the case, fluoroscopic-guided celiac plexus neurolysis was performed. The block was performed using the transaortic approach as it reduces radiation exposure.

Refractory chronic abdominal pain as a result of inoperable pancreatic cancer or chronic pancreatitis poses a formidable challenge and can be effectively relieved with celiac axis block or celiac plexus neurolysis (CPN). Percutaneous celiac plexus block (CPB) or computed tomography (CT)-guidance using anterior or posterior approaches has some limitations. However, endoultrasound (EUS)-guided CPB has evolved itself as an effective and safe procedure for management of refractory abdominal pain. The EUS offers advantages, which include accurate anatomic imaging, real-time monitoring of injection, and anterior approach, which avoids neurologic complications. The CPN can be combined with staging and fine-needle aspiration cytology (FNAC) of a malignancy in the same session. The present review discusses anatomic details of celiac axis block, procedure-related details, complications, contraindications, comparison to other modalities, and results of various studies and author’s experience of EUS guided CPB/neurolysis.

Purpose: Assessment of radiologist’s hand dose in CT-guided interventions and determination of influencing factors. Materials and Methods: The following CT-guided interventions were included: Core biopsy, drainage, periradicular therapy, and celiac plexus neurolysis. The hand dose was measured with an immediately readable dosimeter, the EDD-30 (Unfors, Sweden). The default parameters for CT fluoroscopy were 120 kV, 90 mA and a 4 mm slice thickness. All interventions were performed on a 16-slice CT unit (Aquilion 16 Toshiba, Japan). The tumor size, degree of difficulty (1 – 3), level of experience and device parameters (mAs, dose-length product, scan time) were documented. Results: 138 CT-guided interventions (biopsy n = 99, drainage n = 23, pain therapy n = 16) at different locations (lung n = 41, retroperitoneum n = 53, liver n = 25, spine n = 19) were included. The lesion size was 4 – 240 mm (median: 23 mm). The fluoroscopy time per intervention was 4.6 – 140.2 s (median: 24.2 s). The measured hand dose ranged from 0.001 – 3.02 mSv (median: 0.22 mSv). The median hand dose for lung puncture (n = 41) was slightly higher (median: 0.32 mSv, p = 0.01) compared to that for the liver, retroperitoneum and other. Besides physical influencing factors, the degree of difficulty (p = 0.001) and summed puncture depth (p = 0.004) correlated significantly with the hand dose. Conclusion: The median hand dose for different CT-guided interventions was 0.22 mSv. Therefore, the annual hand dose limit would normally only be reached with about 2000 interventions. Key Points: Citation Format

Endoscopic ultrasound-guided celiac plexus neurolysis (EUS-CPN) is a well-established intervention to palliate malignant pain. We report a patient who developed hepatic and splenic infarction and bowel ischemia following EUS-CPN. A 69-year-old man with known lung cancer and pancreatic metastasis was transferred for debilitating, significant epigastric pain for several months. The patient underwent EUS-CPN to palliate the pain. After the procedure, the patient complained continuously of abdominal pain, nausea, and vomiting; hematemesis and hematochezia were newly developed. Abdominal computed tomography revealed infarction of the liver and spleen and ischemia of the stomach and proximal small bowel. On esophagogastroduodenoscopy, hemorrhagic gastroduodenitis, and multiple gastric ulcers were noted without active bleeding. The patient expired on postoperative day 27 despite the best supportive care.

Background and study aims: No prospective comparison of endoscopic ultrasonography-guided direct celiac ganglia neurolysis (EUS – CGN) vs. EUS-guided celiac plexus neurolysis (EUS – CPN) has been reported. The aim of the current study was to compare the effectiveness of EUS – CGN and EUS – CPN in providing pain relief from upper abdominal cancer pain in a multicenter randomized controlled trial. Patients and methods: Patients with upper abdominal cancer pain were randomly assigned to treatment using either EUS – CGN or EUS – CPN. Evaluation was performed at Day 7 postoperatively using a pain scale of 0 to 10. Patients for whom pain decreased to ≤ 3 were considered to have a positive response, and those experiencing a decrease in pain to ≤ 1 were considered to be completely responsive. Comparison between the two groups was performed using intention-to-treat analysis. The primary endpoint was the difference in treatment response rates between EUS – CGN and EUS – CPN at postoperative Day 7. Secondary endpoints included differences in complete response rates, pain scores, duration of pain relief, and incidence of adverse effects. Results: A total of 34 patients were assigned to each group. Visualization of ganglia was possible in 30 cases (88 %) in the EUS – CGN group. The positive response rate was significantly higher in the EUS – CGN group (73.5 %) than in the EUS – CPN group (45.5 %; P = 0.026). The complete response rate was also significantly higher in the EUS – CGN group (50.0 %) than in the EUS – CPN group (18.2 %; P = 0.010). There was no difference in adverse events or duration of pain relief between the two groups. Conclusions: EUS – CGN is significantly superior to conventional EUS – CPN in cancer pain relief. Clinical trial registration: http://www.umin.ac.jp/ctr/index.htm (ID: UMIN-000002536)

Item does not contain fulltext BACKGROUND AND AIMS: There is little evidence that structures targeted during EUS-guided celiac ganglia neurolysis (EUS-CGN) are celiac ganglia and that selective ethanol injection into ganglia is feasible. We aimed to visualize celiac ganglia, confirm that these structures are ganglia, and visualize ethanol spread after EUS-CGN and EUS-guided celiac plexus neurolysis (EUS-CPN). METHODS: First, celiac ganglia were sought during 97 consecutive EUS procedures. Second, ganglia were identified in a prosected human cadaver by placing a linear echoendoscope next to the celiac trunk and removing the underlying tissue for histology. Finally, various EUS-CGN and EUS-CPN techniques were performed in human cadavers; EUS-CGN was performed with 1 mL ethanol in 1 ganglion, 1 mL per ganglion (both low volume), and 4 mL per ganglion (high volume). EUS-CPN was performed with a central (20 mL) and a bilateral (2*10 mL) approach. Transverse sections (75 mum) were obtained and photographed to allow visualization of the spread of ethanol. RESULTS: A total of 204 ganglia were detected in 83 patients. Mean (+/- standard deviation) size of the long axis was 8.1 mm (+/- 7.4 mm). Histology of the removed region in the cadaver showed only nerve cell bodies. After low-volume EUS-CGN in cadavers, ethanol spread well beyond the targeted ganglion. After high-volume EUS-CGN in cadavers, a larger ethanol spread was seen, which also reached unidentified ganglia; the spread was comparable to the spread after EUS-CPN. CONCLUSIONS: Specific EUS-CGN is not feasible because ethanol spreads well beyond the targeted ganglion. Unidentified celiac ganglia are better reached with high-volume EUS-CGN, and this would likely result in a more thorough neurolysis. High-volume EUS-CGN should be preferred to low-volume EUS-CGN.

OBJECTIVES: The objective of guideline was to provide clear and relevant consensus statements to form a practical guideline for clinicians on the indications, optimal technique, safety and efficacy of endoscopic ultrasound guided celiac plexus neurolysis (EUS-CPN).METHODS: Six important clinical questions were determined regarding EUS-CPN. Following a detailed literature review, 6 statements were proposed attempting to answer those questions. A group of expert endosonographers convened in Chicago, United States (May 2016), where the statements were presented and feedback provided. Subsequently a consensus group of 35 expert endosonographers voted based on their individual level of agreement. A strong recommendation required 80% voter agreement. The modified GRADE (Grading of Recommendations Assessment, Development, and Evaluation) criteria were used to rate the strength of recommendations and the quality of evidence.RESULTS: Eighty percent agreement was reached on 5 of 6 consensus statements, 79.4% agreement was reached on the remaining one.CONCLUSIONS: EUS-CPN is efficacious, should be integrated into the management of pancreas cancer pain, and can be considered early at the time of diagnosis of inoperable disease. Techniques may still vary based on operator experience. Serious complications exist, but are rare.

The care of patients with advanced, incurable pancreatic cancer should begin with a skillful delivery of prognosis, exploration of the patient’s values and goals, and a recommendation for goal-directed therapy. Patients’ hope is preserved best by providing an individualized prognosis, offering up-to-date therapy, demonstrating mastery of the patient’s medical condition, and emphasizing good symptom control. Moderate to severe cancer pain should be treated initially with strong opioids rather than weak opioids, and opioid rotation to another agent is recommended when patients experience adverse effects with the first agent. Celiac plexus neurolysis should be considered for patients with predominantly visceral epigastric and upper abdominal pain, as it durably reduces pain scores, opioid requirements, and opioid adverse side effects. Anorexia-cachexia syndrome in advanced cancer is predictive of poorer prognosis. Corticosteroids and progesterone analogs have been proven to increase weight and improve anorexia, but do not increase lean body mass. Mood disorders are common in advanced pancreatic cancer and can masquerade as, or intensify the experience of, other cancer-related symptoms such as pain, dyspnea, nausea, and anorexia. In advanced cancer, somatic symptoms such as fatigue and insomnia are poor predictors of depression, so changes in affect should be assessed instead. When anorexia appears related to untreated depression, mirtazapine may improve appetite, nausea, and weight.

Chronic pancreatitis (CP) represents the progression from a proinflammatory state to irreversible fibrosis. The CP diagnosis consists of abnormal pancreatic imaging coupled with pancreatitis-type upper abdominal pain and/or pancreatic insufficiency. Medical management includes the elimination of modifiable risk factors such as alcohol or smoking, as well as dietary modification. Pain control is initially managed with nonnarcotics and neuropathic medications prior to consideration of a narcotic pain regimen. Endocrine dysfunction is typically treated with oral hypoglycemics and insulin supplementation. Exocrine dysfunction is treated with oral pancreatic enzyme supplementation. Once medical management options are exhausted, pancreatic endotherapy can be considered for CP pain relief. Pancreatic parenchymal disease can be treated with EUS-guided celiac plexus neurolysis. CP-related pancreatic duct (PD) disease with evidence of ductal obstruction can be managed with pancreatic ERCP for ductal decompression. The clinical efficacy of pancreatic endotherapy for CP pain is variable but represents a less invasive therapeutic option compared to surgery.

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 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.

Introduction Cancer-related abdominal and pelvic pain is unfortunately common. For instance, up to 70–80% of patients with pancreatic cancer suffer from substantial pain. The treatment of cancer-related pain is challenging, with systemic analgesic therapy being, in general, the first-line treatment. Unfortunately, for up to one-third of patients with pancreatic cancer, pain is not well controlled by such analgesics. Compounding this challenge is the side-effect profile of opiates – including nausea, vomiting, constipation, and sedation – that can paradoxically degrade quality of life. Managing cancer-related pain refractory to such analgesic therapy requires additional strategies that demand a multidisciplinary approach, including surgery, radiation oncology, pain medicine, and interventional radiology. Image-guided neurolysis represents an important strategy in battling cancer-related abdominal and pelvic pain. Celiac plexus neurolysis (CPN) is the most common type and can be a very effective adjunctive therapy; it may have a lasting effect in 70–90% of patients with pain related to abdominal malignancy. The keys to treatment success with image-guided neurolysis are to: (1) review cross-sectional imaging, usually computed tomography (CT); (2) understand the relevant anatomy; (3) inject sufficient volume of neurolytic agent; and (4) ensure adequate spread of neurolytic agent. Although the terms have been used interchangeably, a neurolysis procedure should be distinguished from a “block.” Neurolysis refers to permanent disruption of neural pathways that mediate pain, usually with agents such as ethanol or phenol, whereas a block refers to temporary disruption with local anesthetics or steroids. Neurolytic effects, however, may last no more than 3–6 months due to neural regeneration and tumor growth. Ethanol at a 95–100% concentration is a commonly used neurolytic agent. One disadvantage is transient pain experienced during instillation; lidocaine or bupivacaine may be instilled first or mixed with ethanol to reduce intraprocedural pain. Alternatively, phenol may be used as a neurolytic agent. It has a local anesthetic effect and so intraprocedural pain is less common. However, it is a less potent neurolytic and is more viscous than ethanol, which limits mixing with contrast material. As such, ethanol is the more commonly used agent. Various modalities for imaging guidance have been described, including fluoroscopy, CT, and endoscopic ultrasound. CPN may be performed using CT guidance or CT fluoroscopy given the excellent delineation of anatomic structures as well as spread of contrast agent afforded by CT at the time of neurolysis.

Background: Interventional endoscopic ultrasound (EUS)-guided procedures such as EUS-guided celiac ganglia neurolysis (EUS-CGN) and EUS-guided broad plexus neurolysis (EUS-BPN) were developed to treat abdominal cancer-associated pain; however, these procedures are not always effective. The aim of this study was to explore predictors of pain response in EUS-guided neurolysis for pancreatic cancer-associated pain. Methods: This was a retrospective analysis of prospectively collected data of 112 consecutive patients who underwent EUS-BPN in our institution. EUS-CGN was added in cases of visible celiac ganglia. The neurolytic-spread area was divided into six sections and evaluated by post-procedural computed tomography scanning. Pain intensity was assessed using a visual analog scale (VAS), and a decrease in VAS scores by ⩾3 points after neurolysis was considered a good pain response. Univariable and multivariable logistic regression analyses were performed to explore predictors of pain response at 1 and 4 weeks, and complications. Results: A good pain response was obtained in 77.7% and 67.9% of patients at 1 and 4 weeks, respectively. In the multivariable analysis of these patients, the combination method (EUS-BPN plus CGN) was a significant positive predictive factor at 1 week (odds ratio = 3.69, p = 0.017) and 4 weeks (odds ratio = 6.37, p = 0.043). The numbers of neurolytic/contrast spread areas (mean ± SD) were 4.98 ± 1.08 and 4.15 ± 1.12 in patients treated with the combination method and single method, respectively ( p < 0.001). There was no significant predictor of complications. Conclusions: EUS-BPN in combination with EUS-CGN was a predictor of a good pain response in EUS-guided neurolysis for pancreatic cancer-related pain. The larger number of neurolytic/contrast spread areas may lead to better outcomes in patients receiving combination treatment.

RESUMO JUSTIFICATIVA E OBJETIVOS: A neurólise do plexo celíaco é uma opção de tratamento da dor para pacientes com câncer abdominal refratário a outras abordagens. É acompanhada de reações adversas que são diagnosticadas e tratadas desde que o paciente receba monitorização e acompanhamento imediato após o procedimento. O objetivo deste estudo foi relatar o caso de uma paciente submetida a neurólise de plexo celíaco, evoluindo com sintomas de intoxicação alcoólica aguda diagnosticada na sala de recuperação pós-anestésica. RELATO DO CASO: Paciente do gênero feminino, 43 anos, com neoplasia de cabeça de pâncreas submetida a neurólise de plexo celíaco intraoperatório com 40mL de álcool a 98%, evolui na sala de recuperação pós-anestésica com hipotensão, hipoxemia e confusão mental, sintomas esses revertidos com hidratação por via venosa e elevação de membros inferiores. CONCLUSÃO: A alcoolização do plexo celíaco bloqueia definitivamente a dor visceral de pacientes com neoplasia de pâncreas, porém não está isenta de reações adversas, as quais podem evoluir para complicações graves caso não sejam prontamente diagnosticadas, tornando-se imprescindível o acompanhamento do paciente na sala de recuperação pós-anestésica. ABSTRACT BACKGROUND AND OBJECTIVES: Celiac plexus neurolysis is a pain management option for patients with abdominal cancer refractory to other approaches. It is followed by adverse reactions which may be diagnosed and treated, provided patients are monitored and followed up immediately after the procedure. This study aimed at reporting the case of a patient submitted to celiac plexus neurolysis who evolved with acute alcohol intoxication diagnosed in the post-anesthetic care unit. CASE REPORT: Female patient, 43 years old, with pancreatic head cancer, submitted to intraoperative celiac plexus neurolysis with 40 mL of 98% alcohol. Patient evolved in the post-anesthetic care unit with hypotension, hypoxemia and mental confusion, which were reverted with intravenous hydration and elevation of lower limbs. CONCLUSION: Celiac plexus alcoholization permanently blocks visceral pain of pancreatic cancer patients, however it is not free of adverse reactions, which may evolve to severe complications if not promptly diagnosed, making mandatory the follow up of patients in the post-anesthetic care unit.

Pancreatic and other upper abdominal organ malignancies can produce intense visceral pain syndromes that are frequently treated with splanchnic nerve neurolysis (SNN) or celiac plexus neurolysis (CPN). Although commonly performed with either alcohol or phenol, there is scant literature on the comparative effectiveness, duration of benefit, and complication profile comparing the 2 agents. This study presents a retrospective chart review of 93 patients who underwent SNN for cancer-related abdominal pain in order to describe patient characteristics, examine comparative efficacy, duration of benefit, and incidence of complications with alcohol vs. those of phenol. Consistent with previous studies, SNN reduced reported pain scores while not significantly reducing opioid consumption. No difference in pain outcomes was found comparing alcohol versus phenol based neurolytic techniques. Celiac axis tumor infiltration and pre-procedural local radiation therapy did not change the effectiveness of the procedure. Our data demonstrated that 44.57% of patients had ≥ 30% pain reduction while 43.54% did not have pain reduction. Interestingly, the procedure produced significant improvements in anxiety, depression, difficulty thinking clearly, and feeling of well-being. In addition, no difference in complications was seen between the agents either. SNN was an effective and relatively safe procedure for the treatment of pain associated with pancreatic and other upper abdominal organ malignancies in our sample of patients. Choice of neurolytic agent can appropriately be left to the clinical judgment and local availability of the treating physician. The change in ancillary symptoms has a theoretical basis that supports a biopsychosocial model of pain since changes in one target area (pain) impact other related ones (depression and anxiety). Key words: Celiac plexus, splanchnic nerves, neurolysis, nerve block, alcohol, ethanol, phenol, pain, cancer pain, abdominal pain, visceral pain, symptom assessment

Pancreatic cancer is the fourth leading cause of cancer mortality for both men and women in the United States. Overall 5-year survival from time of diagnosis is less than 5%. The only meaningful chance for cure results from early detection while the tumor remains resectable without locoregional extension or metastasis. Endoscopic ultrasound (EUS) is uniquely suited to the examination and treatment of the pancreas. Endoscopic ultrasound can provide important information with regard to disease stage including involvement of the mesenteric vasculature, adjacent organ invasion, and regional lymph node metastasis. In addition, EUS is considered the procedure of choice for tissue diagnosis of pancreatic cancer. More recently, EUS has developed therapeutic roles in an array of other clinical situations including EUS-guided fine needle injection, EUS-guided biliary drainage, celiac plexus neurolysis, brachytherapy, fiducial placement, and emerging antitumor agents delivered directly into the tumor.

Background Celiac plexus neurolysis for the palliative reduction of pain in unresectable pancreatic carcinoma (PC) is safe but provides limited relief. In a previous study, we found that EUS-guided implantation of iodine-125 ( 125 I) around the celiac ganglia is a safe procedure and can induce apoptosis of local neurons in a porcine model. Objective To evaluate the safety and efficacy of direct celiac ganglion irradiation with 125 I seeds for the relief of moderate to severe pain secondary to unresectable PC. Design Prospective study. Setting Single, tertiary care referral center. Patients This study enrolled consecutive patients who had moderate to severe pain resulting from biopsy-proven unresectable PC. Intervention All patients underwent EUS-guided direct celiac ganglion irradiation with 125 I seeds. Follow-up was conducted at least once weekly until death. Main Outcome Measurements Blood parameters, Visual Analog Scale (VAS) score, mean analgesic (MS Contin [morphine sulfate]) consumption, and complications were evaluated during follow-up. Results Twenty-three patients with unresectable PC underwent the procedure. The mean number of seeds implanted in the celiac ganglion per patient was 4 (range 2-6). Immediately after the procedure, pain relief and analgesic consumption showed no significant changes compared with preoperative values. Six patients (26%) reported pain exacerbation. Two weeks later, the VAS score and mean analgesic consumption were significantly less than preoperative values. No procedure-related deaths or major complications occurred. Limitations Uncontrolled study. Conclusions EUS-guided direct celiac ganglion irradiation with 125 I seeds can reduce the VAS score and analgesic drug consumption in patients with unresectable PC.

Background A needle made of nitinol has been developed with enhanced flexibility to overcome the limitations of the currently available 19-G EUS-FNA needles. Objective Evaluate the ability to perform transduodenal FNAs, procure histologic specimens, and undertake therapeutic interventions using the flexible 19-G needle. Design Prospective cohort study. Setting Tertiary-care academic medical center. Patients Consecutive patients with subepithelial masses, pancreatic head or uncinate lesions, or lesions adjacent to the pancreatic head, and patients undergoing therapeutic intervention. Interventions Perform tissue acquisition and interventions with the flexible 19-G FNA needle. Main Outcome Measures Evaluate the ability to perform transduodenal passes with the flexible 19-G FNA needle. Also, assess the utility of the needle to yield both cytologic and histologic samples and to perform therapeutic interventions. Results Of the 50 patients enrolled, tissue acquisition was undertaken in 38 and therapeutic intervention in 12. Of 38 patients from whom tissue was procured, 32 tissue samples were from pancreatic head/uncinate or peripancreatic masses and 6 were from subepithelial masses. Tissue acquisition, which included transduodenal passes, was successful and adequate for cytologic assessment in all 38 patients (100%). Satisfactory histologic specimens were procured from 36 of 38 (94.7%) patients. An onsite diagnosis was established in 35 of 38 (92.1%) patients. In 3 patients with indeterminate/suspicious lesions, a definitive diagnosis was established at histology. A mean of 1.45 ± 0.79 passes per patient was performed. All 12 therapeutic interventions were successful (100%) and included pseudocyst drainage in 5, pelvic abscess drainage in 2, fiducial placement in 2, celiac plexus neurolysis in 2, and cholangiogram in 1. Needle dysfunction or procedural complications were not encountered. Limitations Single-center study with limited power. Conclusions Preliminary data suggest that the flexible 19-G needle can be used for procuring cytologic aspirates and histologic specimens and to undertake therapeutic interventions even by the transduodenal route. Confirmatory studies are required in a larger cohort of patients with varied pathologic conditions to validate these findings.

Background: Celiac plexus neurolysis (CPN) is an effective but temporary management tool for pancreatic cancer pain (PCP). Clinical studies have shown the duration of benefit with initial CPN to be apaproximately 3 months. When pain recurs, CPN may be repeated, but the outcomes for repeat CPN are not well established. The objective of this study is to determine the success rate and duration of relief following repeat celiac plexus neurolysis (rCPN) for PCP. Methods: Patients who underwent rCPN were identified from a database and their records reviewed. Responses of rCPN were then compared with iCPN for success rates and duration of relief. Success was defined as ≥ 50% pain relief lasting ≥ 1 month. Results: Overall, there were 24 rCPN performed. The success rate decreased from 67% after initial CPN to 29% following rCPN (P = 0.13). The mean duration of pain relief decreased in parallel from 3.4 months (iCPN) to 1.6 months (rCPN) (P = 0.03). Among those who had a successful rCPN, 2.9 months elapsed from iCPN to rCPN, with disease progression noted in 29%. In those who failed rCPN, 7.8 months elapsed, with disease progression apapreciated in 71% of cases. Conclusions: rCPN does not provide as much pain relief as iCPN. Disease progression as detailed on imaging appears to be a major factor in the limitations of rCPN. Further prospective studies are warranted to confirm these results and investigate the utility of rCPN.

Both endoscopic retrograde cholangiopancreatography (ERCP) and endoscopic ultrasound (EUS) play critical roles in the diagnosis and management of a wide variety of pancreatic disorders from pancreatitis to pancreatic cancer. ERCP has become primarily a therapeutic procedure for managing both acute and chronic pancreatitis and their complications, whereas EUS mainly provides diagnosis of chronic pancreatitis, pancreatic cysts, and pancreatic masses. EUS has begun to enter therapeutics with endoscopic cystgastrostomy, necrosectomy, celiac plexus neurolysis/block, and as an adjunct to ERCP to gain access to the pancreatic duct.

There is no doubt that our long-range goal is to cure pancreatic cancer. Realistically, most of what we can do currently is treat the disabling symptoms of this dreadful disease. Biliary decompression, intestinal stenting, celiac plexus neurolysis, and fiducial placement are some of the endoscopic procedures that aim to provide better quality of life to patients suffering from this disease. A thorough understanding of these options will help patients make good decisions in choosing the proper treatment. Endoscopists who perform these procedures must possess great skills, but importantly, they must also be compassionate and act with good judgment.

Pancreatic cancer continues to be a diagnostic and therapeutic challenge. The advent of endoscopic ultrasound-guided interventions have brought about a paradigm shift in the endoscopic approach to diagnosis, treatment and palliation of this common malignancy. The last decade has witnessed significant advances in techniques of endoscopic biliary drainage, endoluminal stenting, celiac plexus neurolysis and image-guided radiation therapy, which have transformed the scope of palliation in pancreatic cancer. Moreover, endoscopic ultrasound-aided intratumoral delivery of fiducials, radioisotopes and chemotherapeutic agents have shown promising results and warrant further investigation. This review summarizes the recent advances in endoscopic applications for the management of pancreatic neoplasms.

Purpose Celiac plexus neurolysis (CPN) is currently used as salvage therapy for morphine-resistant pancreatic cancer pain. Endoscopic ultrasound–guided CPN (EUS-CPN) can be performed early, at the time of EUS. We hypothesized that early EUS-CPN would reduce pain and morphine consumption, increase quality of life (QOL), and prolong survival. Patients and Methods Patients were eligible if referred for EUS for suspected pancreatic cancer with related pain. If EUS and EUS-guided fine-needle aspiration cytology confirmed inoperable adenocarcinoma, patients were randomly assigned to early EUS-CPN or conventional pain management. Pain scores (7-point Likert scale), morphine equivalent consumption, and QOL scores (Digestive Disease Questionnaire-15) were assessed at 1 and 3 months. Results Five hundred eighty eligible patients were seen between April 2006 and December 2008. Ninety-six patients were randomly assigned (48 patients per study arm). Pain relief was greater in the EUS-CPN group at 1 month and significantly greater at 3 months (difference in mean percent change in pain score = −28.9 [95% CI, −67.0 to 2.8], P = .09, and −60.7 [95% CI, −86.6 to −25.5], P = .01, respectively). Morphine consumption was similar in both groups at 1 month (difference in mean change in morphine consumption = −1.0 [95% CI, −47.7 to 49.2], P = .99), but tended toward lower consumption at 3 months in the neurolysis group (difference in mean change in morphine consumption = −49.5 [95% CI, −127.5 to 7.0], P = .10). There was no effect on QOL or survival. Conclusion Early EUS-CPN reduces pain and may moderate morphine consumption in patients with painful, inoperable pancreatic adenocarcinoma. EUS-CPN can be considered in all such patients at the time of diagnostic and staging EUS.