Chronic Pancreatitis Pain

Intrathecal Pump vs TPAIC

Top-Line Summary:

A small, single center, retrospective cohort study at a US hospital looked at patients with chronic pancreatitis who were treated with 1.) intrathecal morphine pump (n=13) or 2.) total pancreatectomy with autologous islet cell transplant (n=30). Both lead to clinically significant pain relief and a large decrease in MME. Surgical treatment, even with islet cell transplant, has increased risk of developing post-operative insulin-dependent diabetes (about 46% of patients at 5-year follow-up per a different study).

Medline Search (6/5/24)

Prescription opioids induced microbial dysbiosis worsens severity of chronic pancreatitis and drives pain hypersensitivity

Source

  Gut Microbes. 16(1):2310291, 2024 Jan-Dec.

Authors

  Kesh K; Tao J; Ghosh N; Jalodia R; Singh S; Dawra R; Roy S

Abstract

  Opioids, such as morphine and oxycodone, are widely used for pain management associated with chronic pancreatitis (CP); however, their impact on the progression and pain sensitivity of CP has never been evaluated. This report investigates the impact of opioid use on the severity of CP, pain sensitivity, and the gut microbiome. C57BL/6 mice were divided into control, CP, CP with morphine/oxycodone, and either morphine or oxycodone alone groups. CP was induced by administration of caerulein (50ug/kg/h, i.p. hourly x7, twice a week for 10 weeks). The mouse-to-pancreas weight ratio, histology, and Sirius red staining were performed to measure CP severity. Tail flick and paw pressure assays were used to measure thermal and mechanical pain. DNA was extracted from the fecal samples and subjected to whole-genome shotgun sequencing. Germ-free mice were used to validate the role of gut microbiome in sensitizing acute pancreatic inflammation. Opioid treatment exacerbates CP by increasing pancreatic necrosis, fibrosis, and immune-cell infiltration. Opioid-treated CP mice exhibited enhanced pain hypersensitivity and showed distinct clustering of the gut microbiome compared to untreated CP mice, with severely compromised gut barrier integrity. Fecal microbiota transplantation (FMT) from opioid-treated CP mice into germ-free mice resulted in pancreatic inflammation in response to a suboptimal caerulein dose. Together, these analyses revealed that opioids worsen the severity of CP and induce significant alterations in pain sensitivity and the gut microbiome in a caerulein CP mouse model. Microbial dysbiosis plays an important role in sensitizing the host to pancreatic inflammation.

Total pancreatectomy with islet cell transplantation vs intrathecal narcotic pump infusion for pain control in chronic pancreatitis.

Source

  World Journal of Gastroenterology. 22(16):4160-7, 2016 Apr 28.

Authors

  Mokadem M; Noureddine L; Howard T; McHenry L; Sherman S; Fogel EL; Watkins JL; Lehman GA

Abstract

  AIM: To evaluate pain control in chronic pancreatitis patients who underwent total pancreatectomy with islet cell transplantation or intrathecal narcotic pump infusion.

   METHODS: We recognized 13 patients who underwent intrathecal narcotic pump (ITNP) infusion and 57 patients who underwent total pancreatectomy with autologous islet cell transplantation (TP + ICT) for chronic pancreatitis (CP) pain control between 1998 and 2008 at Indiana University Hospital. All patients had already failed multiple other modalities for pain control and the decision to proceed with either intervention was made at the discretion of the patients and their treating physicians. All patients were evaluated retrospectively using a questionnaire inquiring about their pain control (using a 0-10 pain scale), daily narcotic dose usage, and hospital admission days for pain control before each intervention and during their last follow-up.

   RESULTS: All 13 ITNP patients and 30 available TP + ICT patients were evaluated. The mean age was approximately 40 years in both groups. The median duration of pain before intervention was 6 years and 7 years in the ITNP and TP + ICT groups, respectively. The median pain score dropped from 8 to 2.5 (on a scale of 0-10) in both groups on their last follow up. The median daily dose of narcotics also decreased from 393 mg equivalent of morphine sulfate to 8 mg in the ITNP group and from 300 mg to 40 mg in the TP + ICT group. No patient had diabetes mellitus (DM) before either procedure whereas 85% of those who underwent pancreatectomy were insulin dependent on their last evaluation despite ICT.

   CONCLUSION: ITNP and TP + ICT are comparable for pain control in patients with CP however with high incidence of DM among those who underwent TP + ICT. Prospective comparative studies and longer follow up are needed to better define treatment outcomes.

Pharmacological management of pain in chronic pancreatitis. [Review]

Source

  Scottish Medical Journal. 59(1):71-9, 2014 Feb.

Authors

  Paisley P; Kinsella J

Abstract

  INTRODUCTION: Chronic pancreatitis is a condition that is rising in incidence in the Western World. It is predominated by severe intractable abdominal pain that presents a significant impact on patients' quality of life and physical functioning. The pain is persistent in many patients, requiring admission to hospital for the majority at some stage in their illness. There is no current NICE or SIGN guideline with associated grading for the pharmacological management of this symptom. This paper aims to investigate and summarise the current pharmacological therapies for pain control in an attempt to formulate the levels of evidence supporting their use.

   METHODS: The online digital archives PubMed, Science Direct, Medscape and the Cochrane Library were searched for the keywords pain and chronic pancreatitis. Hand searches of relevant journals and citations were used to complete the investigation of current literature on the topic. Relevant articles and studies were critically analysed in a standard format with relation to study type, population, number, end point and outcomes. Publications not relevant to the management of pain in chronic pancreatitis were excluded.

   RESULTS: Medical therapies, including oral analgesics and enzyme preparations, were included in the analysis of current modalities for treating pain in chronic pancreatitis.

   CONCLUSIONS: A summary of the evidence base for different pharmacological treatments in the context of chronic pancreatitis has shown that large number trials evaluating their efficacy in managing pain are lacking and offer scope for future research on this topic. The use of 'alternative' treatments such as antioxidant preparations and enzyme antagonists has shown promise. With regard to opioids, tramadol is as effective as morphine with less neuropsychiatric and gastrointestinal side effects. Oxycodone may derive more benefit than morphine due to an additional Kappa-agonist effect.

Systematic review of total pancreatectomy and islet autotransplantation for chronic pancreatitis. [Review]

Source

  British Journal of Surgery. 99(6):761-6, 2012 Jun.

Authors

  Bramis K; Gordon-Weeks AN; Friend PJ; Bastin E; Burls A; Silva MA; Dennison AR

Abstract

  BACKGROUND: Total pancreatectomy and islet autotransplantation (TP/IAT) is a treatment option in a subset of patients with chronic pancreatitis. A systematic review of the literature was performed to evaluate the outcome of this procedure, with an attempt to ascertain when it is indicated.

   METHODS: MEDLINE (1950 to present), Embase (1980 to present) and the Cochrane Library were searched to identify studies of outcomes in patients undergoing TP/IAT. Cohort studies that reported the outcomes following the procedure were included. The MOOSE guidelines were used as a basis for this review.

   RESULTS: Five studies met the inclusion criteria. The techniques reported for pancreatectomy and islet cell isolation varied between studies. TP/IAT was successful in reducing pain in patients with chronic pancreatitis. Comparing morphine requirements before and after the procedure, two studies recorded significant reductions. Concurrent IAT reduced the insulin requirement after TP; the rate of insulin independence ranged from 46 per cent of patients at 5 years' mean follow-up to 10 per cent at 8 years. The impact on quality of life was poorly reported. The studies reviewed did not provide evidence for optimal timing of TP/IAT in relation to the evolution of chronic pancreatitis.

   CONCLUSION: This systematic review showed that TP/IAT had favourable outcomes with regard to pain reduction. Concurrent IAT enabled a significant proportion of patients to remain independent of insulin supplementation. Copyright © 2012 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.

Recent Articles in CP Pain Management

Database: Ovid MEDLINE(R) ALL <1946 to June 18, 2024> Search Strategy:

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1 Pancreatitis, Chronic/ (5857) 2 Pain Management/ (42465) 3 1 and 2 (124) 4 from 3 keep 1,3,5-6,9-10,12,17,20-22,26,28,34,40,48 (16)

Extracorporeal Shock-Wave Lithotripsy and Endoscopy for the Treatment of Pain in Chronic Pancreatitis : A Sham-Controlled, Randomized Trial.

Source

 Annals of Internal Medicine. 177(6):749-758, 2024 Jun.

Authors

 Talukdar R; Olesen SS; Unnisa M; Bedarkar A; Sarkar S; Tandan M; Jagtap N; Darisetty S; Kiran S; Koppoju V; Lakhtakia S; Ramchandani M; Kalapala R; Gupta R; Singh VK; Rao GV; Reddy DN; Drewes AM

Abstract

 BACKGROUND: No randomized controlled trials have substantiated endoscopic decompression of the pancreatic duct in patients with painful chronic pancreatitis.

  OBJECTIVE: To investigate the pain-relieving effect of pancreatic duct decompression in patients with chronic pancreatitis and intraductal stones.

  DESIGN: 24-week, parallel-group, randomized controlled trial (ClinicalTrials.gov: NCT03966781).

  SETTING: Asian Institute of Gastroenterology in India from February 2021 to July 2022.

  PARTICIPANTS: 106 patients with chronic pancreatitis.

  INTERVENTION: Combined extracorporeal shock-wave lithotripsy (ESWL) and endoscopic retrograde pancreatography (ERP) compared with sham procedures.

  MEASUREMENTS: The primary end point was pain relief on a 0- to 10-point visual analog scale (VAS) at 12 weeks. Secondary outcomes were assessed after 12 and 24 weeks and included 30% pain relief, opioid use, pain-free days, questionaries, and complications to interventions.

  RESULTS: 52 patients in the ESWL/ERP group and 54 in the sham group were included. At 12 weeks, the ESWL/ERP group showed better pain relief compared with the sham group (mean difference in change, -0.7 [95% CI, -1.3 to 0] on the VAS; P = 0.039). The difference between groups was not sustained at the 24-week follow-up, and no differences were seen for 30% pain relief at 12- or 24-week follow-up. The number of pain-free days was increased (median difference, 16.2 days [CI, 3.9 to 28.5 days]), and the number of days using opioids was reduced (median difference, -5.4 days [CI, -9.9 to -0.9 days]) in the ESWL/ERP group compared with the sham group at 12-week follow-up. Safety outcomes were similar between groups.

  LIMITATION: Single-center study and limited duration of follow-up.

  CONCLUSION: In patients with chronic pancreatitis and intraductal stones, ESWL with ERP provided modest short-term pain relief.

Publication Type

 Journal Article. Randomized Controlled Trial.

Surgery versus Endoscopy for the Management of Painful Chronic Pancreatitis: A Systematic Review and Meta-Analysis of Randomized Trials.

Source

 Digestive Surgery. 41(1):1-11, 2024.

Authors

 Cassar N; Cromwell P; Duggan S; van Veldhuisen C; Boermeester M; Besselink M; Conlon K

Abstract

 BACKGROUND: Debate exists regarding the optimal treatment for painful chronic pancreatitis (CP). This meta-analysis aims to determine the outcomes of surgical intervention as compared to endoscopy in patients with painful CP.

  METHODS: A systematic review and meta-analysis including studies from PubMed, Embase, Web of Science, and Cochrane Databases (1995 onwards) was done by two independent reviewers using PRISMA guidelines. Primary outcome was pain relief.

  RESULTS: Among 8,479 studies, three were randomized trials, comprising a total of 199 patients. Compared with endoscopy, surgery was associated with a lower Izbicki score, both at medium term (mean difference (MD) 21.46, 95% confidence interval (CI) 13.48-29.43, p < 0.00001) and long term (MD: 17.80, 95% CI: 8.36-27.23, p = 0.0002). A higher proportion of surgical patients had some sort of pain relief compared with those who had endoscopy, both at medium term (72% vs. 46%, RR: 1.51, 95% CI: 1.19-1.90, p = 0.0006) and long term (73% vs. 47%, RR: 1.50, 95% CI: 1.19-1.89, p = 0.0007). Complete pain relief was more common in the surgical group compared to the endoscopy group, both at medium term (33% vs. 17%, RR: 1.97, 95% CI: 1.16-3.36, p = 0.01) and long term (35% vs. 18%, RR: 1.92, 95% CI: 1.15-3.20, p = 0.01). The pooled crossover rate from endoscopy to surgery was 22% (22/99).

  CONCLUSIONS: Surgical treatment in patients with painful CP leads to better pain control, requiring fewer interventions as compared to endoscopic treatment. Copyright © 2024 S. Karger AG, Basel.

Publication Type

 Systematic Review. Meta-Analysis.

Etiology, Diagnosis, and Modern Management of Chronic Pancreatitis: A Systematic Review.

Source

 JAMA Surgery. 158(6):652-661, 2023 06 01.

Authors

 Cohen SM; Kent TS

Abstract

 Importance: The incidence of chronic pancreatitis is 5 to 12 per 100000 adults in industrialized countries, and the incidence is increasing. Treatment is multimodal, and involves nutrition optimization, pain management, and when indicated, endoscopic and surgical intervention.

  Objectives: To summarize the most current published evidence on etiology, diagnosis, and management of chronic pancreatitis and its associated complications.

  Evidence Review: A literature search of Web of Science, Embase, Cochrane Library, and PubMed was conducted for publications between January 1, 1997, and July 30, 2022. Excluded from review were the following: case reports, editorials, study protocols, nonsystematic reviews, nonsurgical technical publications, studies pertaining to pharmacokinetics, drug efficacy, pilot studies, historical papers, correspondence, errata, animal and in vitro studies, and publications focused on pancreatic diseases other than chronic pancreatitis. Ultimately, the highest-level evidence publications were chosen for inclusion after analysis by 2 independent reviewers.

  Findings: A total of 75 publications were chosen for review. First-line imaging modalities for diagnosis of chronic pancreatitis included computed tomography and magnetic resonance imaging. More invasive techniques such as endoscopic ultrasonography allowed for tissue analysis, and endoscopic retrograde cholangiopancreatography provided access for dilation, sphincterotomy, and stenting. Nonsurgical options for pain control included behavior modification (smoking cessation, alcohol abstinence), celiac plexus block, splanchnicectomy, nonopioid pain medication, and opioids. Supplemental enzymes should be given to patients with exocrine insufficiency to avoid malnutrition. Surgery was superior to endoscopic interventions for long-term pain control, and early surgery (<3 years from symptom onset) had more superior outcomes than late surgery. Duodenal preserving strategies were preferred unless there was suspicion of cancer.

  Conclusions and Relevance: Results of this systematic review suggest that patients with chronic pancreatitis had high rates of disability. Strategies to improve pain control through behavioral modification, endoscopic measures, and surgery must also accompany management of the sequalae of complications that arise from endocrine and exocrine insufficiency.

Publication Type

 Systematic Review. Journal Article.

Endoscopy versus early surgery for the management of chronic pancreatitis: a systematic review and meta-analysis. [Review]

Source

 Surgical Endoscopy. 36(12):8753-8763, 2022 12.

Authors

 Boregowda U; Echavarria J; Umapathy C; Rosenkranz L; Sayana H; Patel S; Saligram S

Abstract

 BACKGROUND AND AIM: Endoscopic stone removal and stenting of pancreatic strictures are the initial treatment for treating chronic pancreatitis-related pain. Surgery is considered when endoscopic interventions fail to improve symptoms. In this meta-analysis, we have compared early surgery versus endoscopic interventions.

  METHODS: The study was performed as per the PRISMA statement. The literature search was conducted on online databases to identify studies that compared endoscopy and surgery for the management of chronic pancreatitis symptoms. Primary outcomes of interest were pain relief, complications, and exocrine/endocrine insufficiency. Secondary outcomes were mean length of stay and mean number of procedures. Pooled odds ratio (OR) was calculated using random-effects model with 95% confidence interval (CI).

  RESULTS: Of a total of 9880 articles that were screened, three randomized controlled trials and two retrospective studies with 602 patients (71.4% males) were found to be eligible. Endoscopic interventions were performed in 317 patients and 285 patients underwent early surgery. Early surgery provided significantly better pain relief compared to endoscopy (OR 0.46; 95%CI 0.27-0.80; p = 0.01; I2 = 17.65%) and required less number of procedures (Mean difference 1.66; 95%CI 0.9-2.43; p = 0.00; I2 = 96.46%). There was no significant difference in procedure-related complication (OR 0.91; 95%CI 0.51-1.61; p = 0.74; I2 = 38.8%), endocrine (OR 1.18; 95%CI 0.63-2.20; p = 0.61; I2 = 28.24%), or exocrine insufficiency (OR 1.78; 95%CI 0.66-4.79; p = 0.25; I2 = 30.97%) or the length of stay (Mean difference 1.21; 95%CI -7.12 to 4.70; p = 0.69).

  CONCLUSION: Compared to endoscopy, early surgery appears to be better in controlling chronic pancreatitis-related pain, with no significant difference in procedure-related complications. However, larger randomized controlled trials are needed to ascertain their efficacy. Copyright © 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

Publication Type

 Meta-Analysis. Systematic Review. Journal Article. Review.

A meta-analysis of the long-term outcomes following surgery or endoscopic therapy for chronic pancreatitis.

Source

 Langenbecks Archives of Surgery. 407(6):2233-2245, 2022 Sep.

Authors

 Hughes DL; Hughes I; Silva MA

Abstract

 PURPOSE: Refractory abdominal pain is a cardinal symptom of chronic pancreatitis (CP). Management strategies revolve around pain mitigation and resolution. Emerging evidence from observational studies highlights that surgery may result in superior pain relief when compared to endoscopic therapy; however, its impact on long-term quality of life or functional outcome has yet to be determined.

  METHODS: A search through MEDLINE, PubMed and Web of Science was performed for RCTs that compared endoscopic treatment with surgery for the management of CP. The main outcome measure was the impact on pain control. Secondary outcome measures were the effect on quality of life and the incidence rate of new onset exocrine and endocrine failure. Data was pooled for analysis using either an odds ratio (OR) or mean difference (MD) with a random effects model.

  RESULTS: Three RCTs were included with a total of 267 patients. Meta-analysis demonstrated that operative treatment was associated with a significantly higher rate of complete pain control (37%) when compared to endoscopic therapy (17%) [OR (95% confidence interval (CI)) 2.79 (1.53-5.08), p = 0.0008]. No difference was noted in the incidence of new onset endocrine or exocrine failure between treatment strategies.

  CONCLUSION: Surgical management of CP results in a greater extent of complete pain relief during long-term follow-up. Further research is required to evaluate the impact of the time interval between diagnosis and intervention on exocrine function, combined with the effect of early up-front islet auto-transplantation in order to determine whether long-term endocrine function can be achieved. Copyright © 2022. The Author(s).

Publication Type

 Journal Article. Meta-Analysis.

Chronic Pancreatitis. [Review]

Source

 New England Journal of Medicine. 386(9):869-878, 2022 Mar 03.

Authors

 Vege SS; Chari ST

Publication Type

 Journal Article. Review.

Morphologic Factors Predict Pain Relief Following Pancreatic Head Resection in Chronic Pancreatitis Description of the Chronic Pancreatitis Pain Relief (CPPR) Score. Source

 Annals of Surgery. 273(4):800-805, 2021 04 01.

Authors

 Bachmann K; Melling N; Groteluschen R; Fleischauer A; Reeh M; Ghadban T; Bockhorn M; Izbicki JR

Abstract

 OBJECTIVE: This study analyzes the clinicopathologic findings and their impact on outcome of patients so as to identify which patients benefit most from surgical treatment in chronic pancreatitis, especially in regard to pain relief.

  SUMMARY BACKGROUND DATA: The predominant symptom of chronic pancreatitis is chronic pain resulting in reduced quality of life. It is well known that the main reason for development of the disease is abuse of alcohol and nicotine, but only little data on factors influencing outcome are available.

  METHODS: One thousand one hundred forty-six consecutive patients who underwent surgery for chronic pancreatitis were included. Clinicopathologic data, including morphology of the pancreas in preoperative diagnostics and the histopathologic results, were evaluated. A long-term follow-up including Quality of Life and pain scores was performed. Additionally, we describe the novel Chronic Pancreatitis Pain Relief Score (CPPR-Score) as a tool for prediction of pain relief.

  RESULTS: Overall the rate of pain relief was 79.8% after surgery. The presence of an inflammatory mass in the pancreatic head larger than 4 cm (P < 0.001), presence of a dilated main pancreatic duct of over 4 mm (P < 0.001), histopathologically detected severe calcifications (P = 0.001) and severe fibrosis (P < 0.001) as well as ethanol induced disease (P < 0.001) found to be strong independent prognostic factors for pain relief. The CPPR-Score (0-5 points) proved to be a very good predictive score for pain-relief (P < 0.001).

  CONCLUSIONS: The rate of pain relief after surgical treatment in chronic pancreatitis is high and the commonly used procedures can be performed with acceptable morbidity and mortality. The Chronic Pancreatitis Pain Relief Score allows identifying patients who will benefit most from surgery. Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Publication Type

 Journal Article.

Pain management in chronic pancreatitis incorporating safe opioid practices: Challenge accepted.

Source

 World Journal of Gastroenterology. 27(23):3142-3147, 2021 Jun 21.

Authors

 Shah I; Sheth SG; Kothari DJ

Abstract

 Patients with chronic pancreatitis often experience severe, unrelenting abdominal pain, which can significantly impact their quality of life. Pain control, therefore, remains central to the overall management of chronic pancreatitis. Most of the strategies aimed at treating the pain of chronic pancreatitis are based on expert opinion and vary from one institution to another, as there are no uniform guidelines to direct a stepwise approach towards achieving this goal. In this editorial, we comment on best practice strategies targeted towards pain control in chronic pancreatitis, specifically highlighting the use of opioid medications in this patient population. We discuss various safe and efficacious prescription monitoring practices in this article. Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.

Publication Type

 Editorial.

Pain relief in chronic pancreatitis: endoscopic or surgical treatment? a systematic review with meta-analysis. [Review]

Source

 Surgical Endoscopy. 35(8):4085-4094, 2021 08.

Authors

 Mendieta PJO; Sagae VMT; Ribeiro IB; de Moura DTH; Scatimburgo MVCV; Hirsch BS; Rocha RSP; Visconti TAC; Sanchez-Luna SA; Bernardo WM; de Moura EGH

Abstract

 BACKGROUND AND AIMS: Pain is one of the consequences of chronic pancreatitis (CP) that has the greatest impact on the quality of life of patients. Endoscopic and surgical interventions, by producing a decrease in intraductal pancreatic pressure, can provide pain relief. This is the first systematic review that includes only randomized clinical trials (RTCs) comparing outcomes in the short-term (less than 2 years) and long-term (more than 2 years) between these two types of interventions.

  MATERIAL AND METHODS: A comprehensive search of multiple electronic databases to identify RTCs comparing short and long-term pain relief, procedural complications, and days of hospitalization between endoscopic and surgical interventions was performed following the PRISMA guidelines.

  RESULTS: Three RCTs evaluating a total of 199 patients (99 in the endoscopy group and 100 in the surgery group) were included in this study. Surgical interventions provided complete pain relief, with statistical difference, in the long-term (16,4% vs 35.7%; RD 0.19; 95% CI 0.03-0.35; p = 0.02; I2 = 0%), without significant difference in short-term (17.5% vs 31.2%; RD 0.14; 95% CI -0.01-0.28; p = 0.07; I2 = 0%) when compared to endoscopy. There was no statistical difference in short-term (17.5% vs 28.1%; RD 0.11; 95% CI -0.04-0.25; p = 0.15; I2 = 0%) and long-term (34% vs 41.1%; RD 0.07; 95% CI -0.10-0.24; p = 0.42; I2 0%) in partial relief of pain between both interventions. In the short-term, both complications (34.9% vs 29.7%; RD 0.05; 95% CI -0.10-0.21; p = 0.50; I2 = 48%) and days of hospitalization (MD -1.02; 95% CI -2.61-0.58; p = 0.21; I2 = 0%) showed no significant differences.

  CONCLUSION: Surgical interventions showed superior results when compared to endoscopy in terms of complete long-term pain relief. The number of complications and length of hospitalization in both groups were similar.

Publication Type

 Journal Article. Meta-Analysis. Review. Systematic Review.

Cervical transcutaneous vagal neuromodulation in chronic pancreatitis patients with chronic pain: A randomised sham controlled clinical trial.

Source

 PLoS ONE [Electronic Resource]. 16(2):e0247653, 2021.

Authors

 Muthulingam JA; Olesen SS; Hansen TM; Brock C; Drewes AM; Frokjaer JB

Abstract

 BACKGROUND & AIMS: Chronic abdominal pain is the primary symptom of chronic pancreatitis, but unfortunately it is difficult to treat. Vagal nerve stimulation studies have provided evidence of anti-nociceptive effect in several chronic pain conditions. We investigated the pain-relieving effects of transcutaneous vagal nerve stimulation in comparison to sham treatment in chronic pancreatitis patients.

  METHODS: We conducted a randomised double-blinded, sham-controlled, crossover trial in patients with chronic pancreatitis. Patients were randomly assigned to receive a two-week period of cervical transcutaneous vagal nerve stimulation using the gammaCore device followed by a two-week sham stimulation, or vice versa. We measured clinical and experimental endpoints before and after each treatment. The primary clinical endpoint was pain relief, documented in a pain diary using a visual analogue scale. Secondary clinical endpoints included Patients' Global Impression of Change score, quality of life and Brief Pain Inventory questionnaire. Secondary experimental endpoints included cardiac vagal tone and heart rate.

  RESULTS: No differences in pain scores were seen in response to two weeks transcutaneous vagal nerve stimulation as compared to sham treatment (difference in average pain score (visual analogue scale): 0.17, 95%CI (-0.86;1.20), P = 0.7). Similarly, no differences were seen for secondary clinical endpoints, except from an increase in the appetite loss score (13.9, 95%CI (0.5:27.3), P = 0.04). However, improvements in maximum pain scores were seen for transcutaneous vagal nerve stimulation and sham treatments as compared to their respective baselines: vagal nerve stimulation (-1.3+/-1.7, 95%CI (-2.21:-0.42), P = 0.007), sham (-1.3+/-1.9, 95%CI (-2.28:-0.25), P = 0.018). Finally, heart rate was decreased after two weeks transcutaneous vagal nerve stimulation in comparison to sham treatment (-3.7 beats/min, 95%CI (-6.7:-0.6), P = 0.02).

  CONCLUSION: In this sham-controlled crossover study, we found no evidence that two weeks transcutaneous vagal nerve stimulation induces pain relief in patients with chronic pancreatitis.

  TRIAL REGISTRATION NUMBER: The study is registered at NCT03357029; www.clinicaltrials.gov.

Publication Type

 Clinical Trial. Journal Article. Randomized Controlled Trial. Research Support, Non-U.S. Gov't.

Short- and long-term outcome of Frey procedure for chronic pancreatitis in adults.

Source

 American Journal of Surgery. 222(4):793-801, 2021 Oct.

Authors

 Ray S; Das K; Khamrui S; Jana K; Das R; Kumar D; Ansari Z

Abstract

 OBJECTIVE: To report our experience with Frey procedure (FP) for chronic pancreatitis (CP) in adults.

  METHODS: Adult patients with CP, who underwent a FP between August 2007 and July 2018, were retrospectively reviewed.

  RESULTS: Of the total 138 patients, 95 (69%) were male. The median age at operation was 36.5 years. The median pain-surgery interval was 48 months. Alcohol abuse was identified in 64 (46%) patients. The major indication for surgery was disabling pain (94%). There was no postoperative mortality. Postoperative complications developed in 43 (31%) patients. Median postoperative hospital stay was 9 days. Over a median follow-up of 65 months, 84% of patients had complete pain relief. Continuous pain and high preoperative Izbicki pain score were associated with incomplete pain control. New-onset diabetes and exocrine insufficiency developed in 31% and 27% of patients respectively. Longer duration of disease and previous pancreatic surgery were associated with the development of new-onset diabetes after the FP.

  CONCLUSIONS: Frey procedure is safe with an acceptable perioperative complications and good long-term pain control. Copyright © 2021 Elsevier Inc. All rights reserved.

Publication Type

 Journal Article.

International consensus guidelines on interventional endoscopy in chronic pancreatitis. Recommendations from the working group for the international consensus guidelines for chronic pancreatitis in collaboration with the International Association of Pancreatology, the American Pancreatic Association, the Japan Pancreas Society, and European Pancreatic Club.

Source

 Pancreatology. 20(6):1045-1055, 2020 Sep.

Authors

 Kitano M; Gress TM; Garg PK; Itoi T; Irisawa A; Isayama H; Kanno A; Takase K; Levy M; Yasuda I; Levy P; Isaji S; Fernandez-Del Castillo C; Drewes AM; Sheel ARG; Neoptolemos JP; Shimosegawa T; Boermeester M; Wilcox CM; Whitcomb DC

Abstract

 BACKGROUND/OBJECTIVES: This paper is part of the international consensus guidelines on chronic pancreatitis, presenting for interventional endoscopy.

  METHODS: An international working group with experts on interventional endoscopy evaluated 26 statements generated from evidence on 9 clinically relevant questions. The Grading of Recommendations Assessment, Development, and Evaluation approach was used to evaluate the level of evidence. To determine the level of agreement, a nine-point Likert scale was used for voting on the statements.

  RESULTS: Strong consensus was obtained for 15 statements relating to nine questions including the recommendation that endoscopic intervention should be offered to patients with persistent severe pain but not to those without pain. Endoscopic decompression of the pancreatic duct could be used for immediate pain relief, and then offered surgery if this fails or needs repeated endoscopy. Endoscopic drainage is preferred for portal-splenic vein thrombosis and pancreatic fistula. A plastic stent should be placed and replaced 2-3 months later after insertion. Endoscopic extraction is indicated for stone fragments remaining after ESWL. Interventional treatment should be performed for symptomatic/complicated pancreatic pseudocysts. Endoscopic treatment is recommended for bile duct obstruction and afterwards surgery if this fails or needs repeated endoscopy. Surgery may be offered if there is significant calcification and/or mass of the pancreatic head. Percutaneous endovascular treatment is preferred for hemosuccus pancreaticus. Surgical treatment is recommended for duodenal stenosis due to chronic pancreatitis.

  CONCLUSIONS: This international expert consensus guideline provides evidenced-based statements concerning indications and key aspects for interventional endoscopy in the management of patients with chronic pancreatitis. Copyright © 2020 IAP and EPC. Published by Elsevier B.V. All rights reserved.

Publication Type

 Guideline. Journal Article.

Effect of Early Surgery vs Endoscopy-First Approach on Pain in Patients With Chronic Pancreatitis: The ESCAPE Randomized Clinical Trial.

Source

 JAMA. 323(3):237-247, 2020 01 21.

Authors

 Issa Y; Kempeneers MA; Bruno MJ; Fockens P; Poley JW; Ahmed Ali U; Bollen TL; Busch OR; Dejong CH; van Duijvendijk P; van Dullemen HM; van Eijck CH; van Goor H; Hadithi M; Haveman JW; Keulemans Y; Nieuwenhuijs VB; Poen AC; Rauws EA; Tan AC; Thijs W; Timmer R; Witteman BJ; Besselink MG; van Hooft JE; van Santvoort HC; Dijkgraaf MG; Boermeester MA

Corporate Author

 Dutch Pancreatitis Study Group

Abstract

 Importance: For patients with painful chronic pancreatitis, surgical treatment is postponed until medical and endoscopic treatment have failed. Observational studies have suggested that earlier surgery could mitigate disease progression, providing better pain control and preserving pancreatic function.

  Objective: To determine whether early surgery is more effective than the endoscopy-first approach in terms of clinical outcomes.

  Design, Setting, and Participants: The ESCAPE trial was an unblinded, multicenter, randomized clinical superiority trial involving 30 Dutch hospitals participating in the Dutch Pancreatitis Study Group. From April 2011 until September 2016, a total of 88 patients with chronic pancreatitis, a dilated main pancreatic duct, and who only recently started using prescribed opioids for severe pain (strong opioids for <=2 months or weak opioids for <=6 months) were included. The 18-month follow-up period ended in March 2018.

  Interventions: There were 44 patients randomized to the early surgery group who underwent pancreatic drainage surgery within 6 weeks after randomization and 44 patients randomized to the endoscopy-first approach group who underwent medical treatment, endoscopy including lithotripsy if needed, and surgery if needed.

  Main Outcomes and Measures: The primary outcome was pain, measured on the Izbicki pain score and integrated over 18 months (range, 0-100 [increasing score indicates more pain severity]). Secondary outcomes were pain relief at the end of follow-up; number of interventions, complications, hospital admissions; pancreatic function; quality of life (measured on the 36-Item Short Form Health Survey [SF-36]); and mortality.

  Results: Among 88 patients who were randomized (mean age, 52 years; 21 (24%) women), 85 (97%) completed the trial. During 18 months of follow-up, patients in the early surgery group had a lower Izbicki pain score than patients in the group randomized to receive the endoscopy-first approach group (37 vs 49; between-group difference, -12 points [95% CI, -22 to -2]; P = .02). Complete or partial pain relief at end of follow-up was achieved in 23 of 40 patients (58%) in the early surgery vs 16 of 41 (39%)in the endoscopy-first approach group (P = .10). The total number of interventions was lower in the early surgery group (median, 1 vs 3; P < .001). Treatment complications (27% vs 25%), mortality (0% vs 0%), hospital admissions, pancreatic function, and quality of life were not significantly different between early surgery and the endoscopy-first approach.

  Conclusions and Relevance: Among patients with chronic pancreatitis, early surgery compared with an endoscopy-first approach resulted in lower pain scores when integrated over 18 months. However, further research is needed to assess persistence of differences over time and to replicate the study findings.

  Trial Registration: ISRCTN Identifier: ISRCTN45877994.

Publication Type

 Comparative Study. Journal Article. Multicenter Study. Randomized Controlled Trial. Research Support, Non-U.S. Gov't.

Ultrasound-Guided Subcostal TAP Block with Depot Steroids in the Management of Chronic Abdominal Pain Secondary to Chronic Pancreatitis: A Three-Year Prospective Audit in 54 Patients.

Source

 Pain Medicine. 21(1):118-124, 2020 01 01.

Authors

 Niraj G; Kamel Y

Abstract

 BACKGROUND: Chronic pancreatitis is a common cause of recurrent chronic abdominal pain that utilizes significant health care resources. Pain in chronic pancreatitis can be of two types. Visceral pain occurs during ongoing pancreatic inflammation. Once pancreatic inflammation subsides, the pain generator can move to the abdominal wall as a result of viscerosomatic convergence and present as abdominal myofascial pain syndrome. Subcostal transversus abdominis plane block is an abdominal plane block that has been proven effective in upper abdominal pain of somatic origin.

  DESIGN: The authors discuss the two distinct types of chronic abdominal pain as a result of pancreatitis and present a prospective audit of a management pathway.

  METHODS: Over a three-year period, 54 patients with chronic abdominal pain as a result of pancreatitis were prospectively audited at a tertiary care university hospital. Patients were offered bilateral subcostal transversus abdominis plane block with depot steroids as the primary interventional treatment in the pathway.

  RESULTS: In patients with myofascial pain secondary to chronic pancreatitis, the block was effective in producing clinically significant pain relief at three months (95%, 20/21) and durable pain relief lasting six months (62%, 13/21). In patients with visceral pain, the block produced a transient benefit lasting two to three weeks in one-third (six of 17).

  CONCLUSIONS: Subcostal transversus abdominis plane block may be an option in the management of abdominal myofascial pain syndrome secondary to chronic pancreatitis. The block is ineffective in producing clinically significant pain relief in the presence of ongoing pancreatic inflammation. Copyright © 2019 American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Publication Type

 Clinical Trial. Journal Article. Research Support, Non-U.S. Gov't.

Study protocol for a randomised double-blinded, sham-controlled, prospective, cross-over clinical trial of vagal neuromodulation for pain treatment in patients with chronic pancreatitis.

Source

 BMJ Open. 9(7):e029546, 2019 08 23.

Authors

 Muthulingam JA; Olesen SS; Hansen TM; Brock C; Drewes AM; Frokjaer JB

Abstract

 INTRODUCTION: The management of chronic pancreatitis (CP) is challenging and requires a personalised approach focused on the individual patient's main symptoms. Abdominal pain is the most prominent symptom in CP, where central pain mechanisms, including sensitisation and impaired pain modulation, often are involved. Recent clinical studies suggest that vagal nerve stimulation (VNS) induces analgesic effects through the modulation of central pain pathways. This study aims to investigate the effect of 2 weeks transcutaneous VNS (t-VNS) on clinical pain in patients with CP, in comparison to the effect of sham treatment.

  METHODS AND ANALYSIS: Twenty-one patients with CP will be enrolled in this randomised, double-blinded, single-centre, sham-controlled, cross-over study. The study has two treatment periods: A 2-week active t-VNS using GammaCore device and a 2-week treatment with a sham device. During both treatment periods, the patients are instructed to self-administer VNS bilaterally to the cervical vagal area, three times per day. Treatment periods will be separated by 2 weeks. During the study period, patients will record their daily pain experience in a diary (primary clinical endpoint). In addition, all subjects will undergo testing which will include MRI, quantitative sensory testing, cardiac vagal tone assessment and collecting blood samples, before and after the two treatments to investigate mechanisms underlying VNS effects. The data will be analysed using the principle of intention to treat.

  ETHICS AND DISSEMINATION: The regional ethics committee has approved the study: N-20170023. Results of the trial will be submitted for publication in peer-reviewed journals.

  TRIAL REGISTRATION NUMBER: The study is registered at www.clinicaltrials.gov: NCT03357029. Copyright © Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Publication Type

 Clinical Trial Protocol. Journal Article. Research Support, Non-U.S. Gov't.

A Role for Total Pancreatectomy and Islet Autotransplant in the Treatment of Chronic Pancreatitis.

Source

 American Journal of Gastroenterology. 113(3):324-326, 2018 03.

Authors

 Bellin MD

Publication Type

 Journal Article.