1
|
Tłustochowicz K, Krajewska A, Kowalik A, Małecka-Wojciesko E. Treatment Strategies for Chronic Pancreatitis (CP). Pharmaceuticals (Basel) 2025; 18:311. [PMID: 40143090 PMCID: PMC11945612 DOI: 10.3390/ph18030311] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2025] [Revised: 02/19/2025] [Accepted: 02/21/2025] [Indexed: 03/28/2025] Open
Abstract
Chronic pancreatitis (CP) and autoimmune pancreatitis (AIP) are diseases with overlapping features, both requiring complex management strategies. CP is characterized by pancreatic exocrine insufficiency (PEI) and pain, with treatment focused on symptom relief through pancreatic enzyme replacement therapy (PERT), pain control, and lifestyle and nutritional changes. However, the standard therapy does not address the underlying inflammation or fibrosis, which drives disease progression. AIP, on the other hand, presents with obstructive jaundice and fibrosis and is classified into two subtypes: Type 1 (AIP-1), linked to IgG4-related disease, and Type 2 (AIP-2), associated with inflammatory bowel disease. Treatment for AIP typically involves oral steroids. Immunomodulators and rituximab are used for recurrent or refractory cases. Novel therapies targeting the inflammation and fibrotic components of CP are being explored. A multidisciplinary approach is essential to optimize care and improve patients' outcomes.
Collapse
Affiliation(s)
| | | | | | - Ewa Małecka-Wojciesko
- Department of Digestive Tract Diseases, Medical University of Lodz, 90-153 Lodz, Poland; (K.T.); (A.K.)
| |
Collapse
|
2
|
Gurria JP, Boucher AA, Hornung L, Palumbo JS, Badia P, Luchtman-Jones L, Abu-El-Haija M, Lin TK, Nathan JD. Thrombopoietin Contributes to Extreme Thrombocytosis After Pediatric Pancreatectomy With Islet Autotransplantation. Pancreas 2019; 48:652-655. [PMID: 31091211 DOI: 10.1097/mpa.0000000000001313] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
OBJECTIVE This study aims to explore the role of thrombopoietin (TPO) production in extreme thrombocytosis that is often observed after pancreatectomy with islet autotransplantation (IAT) and the effectiveness of hydroxyurea in thrombocytosis management. METHODS Retrospective chart review was performed for all patients who underwent pancreatectomy with IAT at our institution between April 1, 2015, and December 31, 2016. Data evaluated included demographics, platelet counts, TPO levels, and thrombocytosis management strategies. RESULTS Twelve total and 1 subtotal pancreatectomy with IAT cases were reviewed. All operations included splenectomy. No major surgical or thrombotic complications occurred. Thrombopoietin levels, normal preoperatively, rose significantly (median, 219 pg/mL) soon after surgery, peaking on median postoperative day 3. Platelet counts, also normal preoperatively, increased within a week of surgery, with 92% over 1000 K/μL (median peak platelet count, 1403 K/μL). Platelet counts and TPO levels dropped after hydroxyurea initiation in most patients. CONCLUSIONS After pancreatectomy with IAT, patients experienced marked TPO rise and subsequent thrombocytosis, and both decreased significantly after hydroxyurea initiation. These data suggest that TPO elevation and associated increased platelet production may be one driver of early extreme post-total pancreatectomy with islet autotransplantation thrombocytosis, and this process may be modulated by hydroxyurea.
Collapse
Affiliation(s)
- Juan P Gurria
- From the Division of Pediatric General and Thoracic Surgery
| | | | - Lindsey Hornung
- Division of Biostatistics and Epidemiology, Cincinnati Children's Hospital
| | | | | | | | | | | | | |
Collapse
|
3
|
Mokadem M, Noureddine L, Howard T, McHenry L, Sherman S, Fogel EL, Watkins JL, Lehman GA. Total pancreatectomy with islet cell transplantation vs intrathecal narcotic pump infusion for pain control in chronic pancreatitis. World J Gastroenterol 2016; 22:4160-4167. [PMID: 27122666 PMCID: PMC4837433 DOI: 10.3748/wjg.v22.i16.4160] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/18/2015] [Revised: 01/20/2016] [Accepted: 02/22/2016] [Indexed: 02/06/2023] Open
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.
Collapse
|
4
|
Francis T, Graf A, Hodges K, Kennedy L, Hargrove L, Price M, Kearney K, Francis H. Histamine regulation of pancreatitis and pancreatic cancer: a review of recent findings. Hepatobiliary Surg Nutr 2014; 2:216-26. [PMID: 24570946 DOI: 10.3978/j.issn.2304-3881.2013.08.06] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/18/2013] [Accepted: 07/25/2013] [Indexed: 12/11/2022]
Abstract
The pancreas is a dynamic organ that performs a multitude of functions within the body. Diseases that target the pancreas, like pancreatitis and pancreatic cancer, are devastating and often fatal to the suffering patient. Histamine and histamine receptors (H1-H4HRs) have been found to play a critical role in biliary diseases. Accordingly, the biliary tract and the pancreas share similarities with regards to morphological, phenotypical and functional features and disease progression, studies related the role of H1-H4HRs in pancreatic diseases are important. In this review, we have highlighted the role that histamine, histidine decarboxylase (HDC), histamine receptors and mast cells (the main source of histamine in the body) play during both pancreatitis and pancreatic cancer. The objective of the review is to demonstrate that histamine and histamine signaling may be a potential therapeutic avenue towards treatment strategies for pancreatic diseases.
Collapse
Affiliation(s)
- Taylor Francis
- Medicine, Scott and White Healthcare, Texas A&M HSC, Temple, TX, USA
| | - Allyson Graf
- Research, Central Texas Veteran's Health Care System, Scott and White Healthcare, Texas A&M HSC, Temple, TX, USA ; Scott & White Digestive Disease Research Center, Scott and White Healthcare, Texas A&M HSC, Temple, TX, USA
| | - Kyle Hodges
- Scott & White Digestive Disease Research Center, Scott and White Healthcare, Texas A&M HSC, Temple, TX, USA
| | - Lindsey Kennedy
- Scott & White Digestive Disease Research Center, Scott and White Healthcare, Texas A&M HSC, Temple, TX, USA
| | - Laura Hargrove
- Scott & White Digestive Disease Research Center, Scott and White Healthcare, Texas A&M HSC, Temple, TX, USA
| | - Mattie Price
- Scott & White Digestive Disease Research Center, Scott and White Healthcare, Texas A&M HSC, Temple, TX, USA
| | - Kate Kearney
- Scott & White Digestive Disease Research Center, Scott and White Healthcare, Texas A&M HSC, Temple, TX, USA
| | - Heather Francis
- Medicine, Scott and White Healthcare, Texas A&M HSC, Temple, TX, USA ; Research, Central Texas Veteran's Health Care System, Scott and White Healthcare, Texas A&M HSC, Temple, TX, USA ; Scott & White Digestive Disease Research Center, Scott and White Healthcare, Texas A&M HSC, Temple, TX, USA
| |
Collapse
|
5
|
Seiler CM, Izbicki J, Varga-Szabó L, Czakó L, Fiók J, Sperti C, Lerch MM, Pezzilli R, Vasileva G, Pap A, Varga M, Friess H. Randomised clinical trial: a 1-week, double-blind, placebo-controlled study of pancreatin 25 000 Ph. Eur. minimicrospheres (Creon 25000 MMS) for pancreatic exocrine insufficiency after pancreatic surgery, with a 1-year open-label extension. Aliment Pharmacol Ther 2013; 37:691-702. [PMID: 23383603 PMCID: PMC3601428 DOI: 10.1111/apt.12236] [Citation(s) in RCA: 61] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/28/2012] [Revised: 12/03/2012] [Accepted: 01/17/2013] [Indexed: 02/05/2023]
Abstract
BACKGROUND Pancreatic exocrine insufficiency (PEI) often occurs following pancreatic surgery. AIM To demonstrate the superior efficacy of pancreatin 25 000 minimicrospheres (Creon 25000 MMS; 9-15 capsules/day) over placebo in treating PEI after pancreatic resection. METHODS A 1-week, double-blind, randomised, placebo-controlled, parallel-group, multicentre study with a 1-year, open-label extension (OLE). Subjects ≥18 years old with PEI after pancreatic resection, defined as baseline coefficient of fat absorption (CFA) <80%, were randomised to oral pancreatin or placebo (9-15 capsules/day: 3 with main meals, 2 with snacks). In the OLE, all subjects received pancreatin. The primary efficacy measure was least squares mean CFA change from baseline to end of double-blind treatment (ancova). RESULTS All 58 subjects randomised (32 pancreatin, 26 placebo) completed double-blind treatment and entered the OLE; 51 completed the OLE. The least squares mean CFA change in the double-blind phase was significantly greater with pancreatin vs. placebo: 21.4% (95% CI: 13.7, 29.2) vs. -4.2% (-12.8, 4.5); difference 25.6% (13.9, 37.3), P < 0.001. The mean ± s.d. CFA increased from 53.6 ± 20.6% at baseline to 78.4 ± 20.7% at OLE end (P < 0.001). Treatment-emergent adverse events occurred in 37.5% subjects on pancreatin and 26.9% on placebo during double-blind treatment, with flatulence being the most common (pancreatin 12.5%, placebo 7.7%). Only two subjects discontinued due to treatment-emergent adverse events, both during the OLE. CONCLUSIONS This study demonstrates superior efficacy of pancreatin 25 000 over placebo in patients with PEI after pancreatic surgery, measured by change in CFA. Pancreatin was generally well tolerated at the high dose administered (EudraCT registration number: 2005-004854-29).
Collapse
Affiliation(s)
- C M Seiler
- Department of General, Visceral and Vascular Surgery, Josephs-Hospital Warendorf, Warendorf, Germany.
| | | | | | | | | | | | | | | | | | | | | | | |
Collapse
|
6
|
Thorat V, Reddy N, Bhatia S, Bapaye A, Rajkumar JS, Kini DD, Kalla MM, Ramesh H. Randomised clinical trial: the efficacy and safety of pancreatin enteric-coated minimicrospheres (Creon 40000 MMS) in patients with pancreatic exocrine insufficiency due to chronic pancreatitis--a double-blind, placebo-controlled study. Aliment Pharmacol Ther 2012; 36:426-36. [PMID: 22762290 PMCID: PMC3528066 DOI: 10.1111/j.1365-2036.2012.05202.x] [Citation(s) in RCA: 49] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/16/2012] [Revised: 03/21/2012] [Accepted: 06/13/2012] [Indexed: 12/15/2022]
Abstract
BACKGROUND Pancreatic exocrine insufficiency (PEI) results in maldigestion, leading to abdominal pain, steatorrhoea, malnutrition and weight loss. AIM To assess the efficacy and safety of pancreatin (Creon 40000 MMS) in treating PEI due to chronic pancreatitis (CP). METHODS This was a 1-week, double-blind, randomised, placebo-controlled, parallel-group, multicentre study in India. Men and women ≥18 years of age with proven CP and PEI [defined as a coefficient of fat absorption (CFA) ≤80% during run-in phase] were randomised 1:1 to pancreatin or placebo (two capsules orally per main meal, one with snacks). The primary outcome measure was change in CFA from baseline to end of double-blind treatment (analysis of covariance). RESULTS Of 62 patients randomised (34 pancreatin, 28 placebo), 61 completed treatment; one patient in the placebo arm withdrew consent before completion. Patient characteristics were similar in both groups except for the proportion of men (pancreatin 82% vs. placebo 68%). Patients receiving pancreatin had a statistically significant greater improvement in fat absorption from baseline to the end of double-blind treatment compared with those receiving placebo, with a least squares mean change (95% CI) in CFA of 18.5% (15.8-21.2) vs. 4.1% (1.0-7.2), respectively. This resulted in a treatment difference of 14.4% (10.3-18.5); P = 0.001. Patients receiving pancreatin also had a statistically significant greater improvement in nitrogen absorption and greater reductions in mean stool fat, stool frequency and stool weight compared with those receiving placebo. Treatment-emergent adverse events occurred in 12 patients on pancreatin and in seven on placebo; none led to study discontinuation. CONCLUSIONS The results provide evidence for the efficacy of pancreatin (Creon 40000 MMS) in patients with pancreatic exocrine insufficiency due to chronic pancreatitis, and confirm that this formulation is well tolerated, with a good safety profile, at the dose administered.
Collapse
Affiliation(s)
- V Thorat
- Department of Medical Gastroenterology, Poona Hospital & Research CentrePune, India
| | - N Reddy
- Department of Medical Gastroenterology, Asian Institute of GastroenterologyHyderabad ,India
| | - S Bhatia
- Department of Gastroenterology Seth G. S. Medical College and KEM HospitalMumbai, India
| | - A Bapaye
- Department of Gastroenterology Deenanath Mangeshkar Hospital & Research CentrePune, India
| | - J S Rajkumar
- Division of Gastroenterology Lifeline Multispeciality HospitalChennai, India
| | - D D Kini
- Manipal AcuNova MHB Clinical Research Centre, Manipal HospitalBangalore, India
| | - M M Kalla
- Department of Gastroenterology,S. R. Kalla Memorial HospitalJaipur, India
| | - H Ramesh
- Department of Surgical Gastroenterology and Liver Transplantation Lakeshore Hospital & Research CentreKochiIndia
| |
Collapse
|
7
|
Gubergrits N, Malecka-Panas E, Lehman GA, Vasileva G, Shen Y, Sander-Struckmeier S, Caras S, Whitcomb DC. A 6-month, open-label clinical trial of pancrelipase delayed-release capsules (Creon) in patients with exocrine pancreatic insufficiency due to chronic pancreatitis or pancreatic surgery. Aliment Pharmacol Ther 2011; 33:1152-61. [PMID: 21418260 DOI: 10.1111/j.1365-2036.2011.04631.x] [Citation(s) in RCA: 76] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
BACKGROUND Pancreatic enzyme replacement therapy (PERT) is necessary to prevent severe maldigestion and unwanted weight loss associated with exocrine pancreatic insufficiency (EPI) due to chronic pancreatitis (CP) or pancreatic surgery (PS). AIM To assess the long-term safety and efficacy of pancrelipase (pancreatin) delayed-release capsules (Creon) in this population. METHODS This was a 6-month, open-label extension of a 7-day, double-blind, placebo-controlled study enrolling patients ≥18 years old with confirmed EPI due to CP or PS who were previously receiving PERT. Patients received individualised pancrelipase doses as directed by investigators (administered as Creon 24 000-lipase unit capsules). RESULTS Overall, 48 of 51 patients completed the open-label phase; one withdrew due to the unrelated treatment-emergent adverse event (TEAE) of cutaneous burns and two were lost to follow-up. The mean age was 50.9 years, 70.6% of patients were male, 76.5% had CP and 23.5% had undergone PS. The mean±s.d. pancrelipase dose was 186960±74640 lipase units/day. TEAEs were reported by 22 patients (43.1%) overall. Only four patients (7.8%) had TEAEs that were considered treatment related. From double-blind phase baseline to end of the open-label period, subjects achieved a mean±s.d. body weight increase of 2.7±3.4 kg (P<0.0001) and change in daily stool frequency of -1.0±1.3 (P<0.001). Improvements in abdominal pain, flatulence and stool consistency were observed. CONCLUSIONS Pancrelipase was well tolerated over 6 months and resulted in statistically significant weight gain and reduced stool frequency in patients with EPI due to CP or PS previously managed with standard PERT.
Collapse
Affiliation(s)
- N Gubergrits
- Department of Internal Diseases, Donetsk National Medical University, Donetsk, Ukraine
| | | | | | | | | | | | | | | |
Collapse
|
8
|
Toskes PP, Secci A, Thieroff-Ekerdt R. Efficacy of a novel pancreatic enzyme product, EUR-1008 (Zenpep), in patients with exocrine pancreatic insufficiency due to chronic pancreatitis. Pancreas 2011; 40:376-82. [PMID: 21343835 DOI: 10.1097/mpa.0b013e31820b971c] [Citation(s) in RCA: 27] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
OBJECTIVES EUR-1008 (ZENPEP® [pancrelipase] Delayed-Release Capsules) delayed-release capsules is a novel, enteric-coated, porcine-derived pancreatic enzyme product. This study evaluated the efficacy and safety of 2 doses of ZENPEP in patients with chronic pancreatitis (CP) and exocrine pancreatic insufficiency (EPI). METHODS The effect of ZENPEP on the coefficient of fat absorption (CFA) was investigated in a randomized, double-blind, dose-response, crossover study with placebo run-in (7-9 days) and 2 treatment periods (9-11 days) composed of a high dose (7 × 20,000 lipase units per day) and a low dose (7 × 5000 lipase units per day). RESULTS Mean CFA was significantly higher with low- (88.9%) and high-dose (89.9%) ZENPEP versus placebo run-in (82%; P < 0.001; n = 72) with no difference between doses (P = 0.228, primary end point). In patients with baseline CFA less than 90% (n = 33), the high dose was significantly more effective (CFA: 84.1%) than the low dose (CFA: 81.1%; P < 0.001). Post hoc analysis revealed an increase in treatment effect with more severe EPI. Coefficient of nitrogen absorption (P < 0.001), body weight (P ≤ 0.021), and body mass index (P ≤ 0.020) also increased significantly with both doses compared with baseline. Percentage of days with EPI symptoms decreased with both doses. CONCLUSIONS Our findings suggest that CP patients with EPI benefit from a low dose of ZENPEP, whereas the high dose might be needed for patients with more severe EPI.
Collapse
Affiliation(s)
- Phillip P Toskes
- Department of Medicine, University of Florida, Gainesville, FL, USA.
| | | | | |
Collapse
|
9
|
Whitcomb DC, Lehman GA, Vasileva G, Malecka-Panas E, Gubergrits N, Shen Y, Sander-Struckmeier S, Caras S. Pancrelipase delayed-release capsules (CREON) for exocrine pancreatic insufficiency due to chronic pancreatitis or pancreatic surgery: A double-blind randomized trial. Am J Gastroenterol 2010; 105:2276-86. [PMID: 20502447 DOI: 10.1038/ajg.2010.201] [Citation(s) in RCA: 136] [Impact Index Per Article: 9.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
OBJECTIVES Pancreatic-enzyme replacement therapy (PERT) is the standard of care to prevent maldigestion, malnutrition, and excessive weight loss in patients with exocrine pancreatic insufficiency (EPI) due to chronic pancreatitis (CP) or pancreatic surgery (PS). Our objective was to assess the efficacy and safety of a new formulation of pancrelipase (pancreatin) delayed-release 12,000-lipase unit capsules (CREON) in patients with EPI due to CP or PS. METHODS This was a double-blind, randomized, multicountry, placebo-controlled, parallel-group trial enrolling patients ≥18 years old with confirmed EPI due to CP or PS conducted in clinical research centers or hospitals. After a 5-day placebo run-in period (baseline), patients were randomized to pancrelipase (72,000 lipase units per meal; 36,000 per snack) or placebo for 7 days. All patients received an individually designed diet to provide at least 100 g of fat per day. The primary efficacy measure was the change in coefficient of fat absorption (CFA) from baseline to end of the double-blind period, analyzed using non-parametric analysis of covariance. Secondary outcomes included the coefficient of nitrogen absorption (CNA), clinical symptoms, and safety parameters. RESULTS In total, 25 patients (median age of 54 years, 76% male) received pancrelipase and 29 patients (median age of 50 years, 69% male) received placebo. Th e mean ± s.d. change from baseline in CFA was significantly greater with pancrelipase vs. placebo: 31.9 ± 18.6 vs. 8.7 ± 12.4 % ( P < 0.0001) [corrected]. Similarly, the mean ± s.d. change from baseline in CNA was greater for pancrelipase vs. placebo: 35.2 ± 29.1 vs. 8.9 ± 28.0 % ( P = 0.0005) [corrected].Greater improvements from baseline in stool frequency, stool consistency, abdominal pain, and flatulence were observed with pancrelipase vs. placebo. Treatment-emergent adverse events (TEAEs) were reported in five patients (20.0%) in the pancrelipase group and in six (20.7%) in the placebo group; the most common were gastrointestinal (GI) events and metabolism/nutrition disorders. There were no treatment discontinuations due to TEAEs. CONCLUSIONS Pancrelipase delayed-release 12,000-lipase unit capsules were effective in treating fat and nitrogen maldigestion with a TEAE rate similar to that of placebo in patients with EPI due to CP or PS.
Collapse
Affiliation(s)
- David C Whitcomb
- Department of Medicine, University of Pittsburgh, Pennsylvania, USA.
| | | | | | | | | | | | | | | |
Collapse
|
10
|
Li ZS, Wang W, Liao Z, Zou DW, Jin ZD, Chen J, Wu RP, Liu F, Wang LW, Shi XG, Yang Z, Wang L. A long-term follow-up study on endoscopic management of children and adolescents with chronic pancreatitis. Am J Gastroenterol 2010; 105:1884-1892. [PMID: 20216535 DOI: 10.1038/ajg.2010.85] [Citation(s) in RCA: 44] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
OBJECTIVES Data on therapeutic endoscopic retrograde cholangiopancreatography (ERCP) for chronic pancreatitis (CP) in children and adolescents, especially with long-term follow-up of consequences, are rarely reported. The aim of this study was to determine the long-term follow-up results of therapeutic ERCP for CP in children and adolescents. METHODS All patients with CP who received therapeutic ERCP at Changhai Hospital from January 1997 to May 2009, with the age at first onset of pain being less than 18.0 years, were included. Attempts were made to contact all adolescents and follow-up data were recorded. Clinical data were assessed before and after every ERCP. RESULTS Follow-up information was available in 42 (91.3%) of the 46 patients who received therapeutic ERCP. There were 20 boys and 22 girls, with the age at first onset being 11.8+/-4.5 years. A total of 110 therapeutic ERCP sessions were performed in the 42 patients. The post-ERCP complication rate was 17.3%, including mild and moderate pancreatitis (n=17) and mild cholangitis (n=2). The mean follow-up period of time was 61.4 (range: 24-132) months. Five patients underwent subsequent surgery because of refractory abdominal pain after endotherapy. Of the remaining 37 patients who received therapeutic ERCP alone, abdominal pain improved in 30 (81.1%) patients, and was completely relieved in 24 (64.9%) patients during the period of follow-up. CONCLUSIONS Therapeutic ERCP may offer long-term improvement in pain in children and adolescents with CP.
Collapse
Affiliation(s)
- Zhao-Shen Li
- Chronic Pancreatic Study Group, Department of Gastroenterology, Digestive Endoscopy Center, Changhai Hospital, The Second Military Medical University, Shanghai, China.
| | | | | | | | | | | | | | | | | | | | | | | |
Collapse
|
11
|
Graff GR, McNamara J, Royall J, Caras S, Forssmann K. Safety and Tolerability of a New Formulation of Pancrelipase Delayed-Release Capsules (CREON®) in Children Under Seven Years of Age with Exocrine Pancreatic Insufficiency due to Cystic Fibrosis. Clin Drug Investig 2010; 30:351-64. [DOI: 10.2165/11533390-000000000-00000] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/29/2023]
|
12
|
Graff GR, Maguiness K, McNamara J, Morton R, Boyd D, Beckmann K, Bennett D. Efficacy and tolerability of a new formulation of pancrelipase delayed-release capsules in children aged 7 to 11 years with exocrine pancreatic insufficiency and cystic fibrosis: a multicenter, randomized, double-blind, placebo-controlled, two-period crossover, superiority study. Clin Ther 2010; 32:89-103. [PMID: 20171415 DOI: 10.1016/j.clinthera.2010.01.012] [Citation(s) in RCA: 44] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/07/2009] [Indexed: 12/17/2022]
Abstract
BACKGROUND Pancreatic enzyme replacement therapy (PERT) is essential for maintaining adequate nutrition in children with exocrine pancreatic insufficiency (EPI) due to cystic fibrosis (CF). The US Food and Drug Administration regulations now require all PERT products to undergo clinical efficacy and safety studies before they can be considered for marketing approval. OBJECTIVE This study was conducted to compare the efficacy of a new formulation of pancrelipase (pancreatin) delayed-release 12,000-lipase unit capsules with placebo in children with EPI due to CF. METHODS This was a multicenter, randomized, double-blind, placebo-controlled, 2-period crossover, superiority study of the new formulation of pancrelipase delayed-release 12,000-lipase unit capsules in children aged 7 to 11 years with CF and EPI. In each period, pancrelipase or identical placebo capsules were taken for 5 days. The primary outcome measure was the coefficient of fat absorption (CFA); secondary outcome measures were the coefficient of nitrogen absorption (CNA) and clinical symptoms. The latter were assessed based on patient-reported daily stool frequency, stool consistency (hard, formed/normal, soft, or watery), flatulence (none, mild, moderate, or severe), and abdominal pain (none, mild, moderate, or severe). Safety measures included vital signs, physical examinations, standard laboratory safety tests (hematology and biochemistry), and adverse events. RESULTS Seventeen patients were randomized to treatment and 16 completed the study; 1 patient withdrew consent during the first treatment period and was not included in the efficacy analysis. Patients' median age was 8.0 years (range, 7-11 years); 12 patients (70.6%) were male. CFA values were significantly greater for pancrelipase compared with placebo, with least squares mean (SE) values of 82.8% (2.7%) and 47.4% (2.7%), respectively (P < 0.001). The results were similar for CNA, with mean values of 80.3% (3.2%) and 45.0% (3.2%) (P < 0.001). Pancrelipase treatment had significantly greater effects on CFA and CNA in patients with a placebo CFA <50% than in those with a placebo CFA >50% (both parameters, P < 0.001 and P = 0.008, respectively). Significant improvements in stool fat, weight, and nitrogen and a significant reduction in daily stool frequency were observed with pancrelipase compared with placebo (all, P < 0.001). Symptoms of EPI were less severe and remained relatively stable during pancrelipase treatment, but worsened slightly during receipt of placebo. Treatment-emergent adverse events were reported in 5 patients (29.4%) during receipt of pancrelipase and in 9 patients (56.3%) during receipt of placebo; these were predominantly gastrointestinal events. There were no discontinuations due to treatment-emergent adverse events and no serious adverse events. CONCLUSIONS In this study in children with EPI due to CF, the new formulation of pancrelipase delayedrelease capsules was associated with improvements in CFA, CNA, stool properties, and EPI symptoms compared with placebo. Pancrelipase delayed-release capsules appeared to be well tolerated. ClinicalTrials.gov identifier: NCT00690820. (Clin Ther.
Collapse
Affiliation(s)
- Gavin R Graff
- Penn State Milton S. Hershey Medical Center, Penn State Medical School, Department of Pediatrics, Hershey, Pennsylvania 17033-0850, USA.
| | | | | | | | | | | | | |
Collapse
|
13
|
Abstract
OBJECTIVE To establish the current status of surgical therapy for chronic pancreatitis, recent published reports are examined in the context of the historical advances in the field. BACKGROUND The basis for decompression (drainage), denervation, and resection strategies for the treatment of pain caused by chronic pancreatitis is reviewed. These divergent approaches have finally coalesced as the head of the pancreas has become apparent as the nidus of chronic inflammation. METHODS The recent developments in surgical methods to treat the complications of chronic pancreatitis and the results of recent prospective randomized trials of operative approaches were reviewed to establish the current best practices. RESULTS Local resection of the pancreatic head, with or without duct drainage, and duodenum-preserving pancreatic head resection offer outcomes as effective as pancreaticoduodenectomy, with lowered morbidity and mortality. Local resection or excavation of the pancreatic head offers the advantage of lowest cost and morbidity and early prevention of postoperative diabetes. The late incidences of recurrent pain, diabetes, and exocrine insufficiency are equivalent for all 3 surgical approaches. CONCLUSIONS Local resection of the pancreatic head appears to offer best outcomes and lowest risk for the management of the pain of chronic pancreatitis.
Collapse
|
14
|
Ma ZH, Ma QY, Sha HC, Wu SL, Wen J. Magnetic resonance cholangiopancreatography for the detection of pancreatic duct stones in patients with chronic pancreatitis. World J Gastroenterol 2009; 15:2543-6. [PMID: 19469007 PMCID: PMC2686915 DOI: 10.3748/wjg.15.2543] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To assess the role of magnetic resonance cholangiopancreatography (MRCP) in detection of pancreatic duct stones (PDS) in patients with chronic pancreatitis (CP).
METHODS: Clinical data of 78 CP patients who were treated at the First Affiliated Hospital of Xi’an Jiaotong University (China) between January 2004 and July 2008 were retrospectively analyzed. A predictive model of pancreatic duct stones was established through logistic regression and its effectiveness was verified. Among these patients, MRCP was performed in 60 patients who served as a control group, while 44 patients with a higher predictive value than the entry threshold of the predictive model served as an experimental group.
RESULTS: The positive rate of PDS in the 78 patients with CP was 19.2% (15/78). The predictive entry threshold of the predictive model was 5% (P < 0.05). The possibility of existence of PDS could be predicted according to the following 4 indexes: gastrointestinal symptoms, intermittent abdominal pain, diabetes mellitus (DM)/impaired glucose tolerance (IGT) and positive B-mode ultrasound results. The incidence of PDS in the experimental group was higher than that in the control group (P < 0.05).
CONCLUSION: MRCP is strongly suggested for the detection of PDS in patients with gastrointestinal symptoms, intermittent abdominal pain, DM/IGT and positive B-mode ultrasound results.
Collapse
|
15
|
Kongkam P, Wagner DL, Sherman S, Fogel EL, Whittaker SC, Watkins JL, McHenry L, Lehman GA. Intrathecal narcotic infusion pumps for intractable pain of chronic pancreatitis: a pilot series. Am J Gastroenterol 2009; 104:1249-55. [PMID: 19367269 DOI: 10.1038/ajg.2009.54] [Citation(s) in RCA: 27] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
OBJECTIVES The aim of this study was to evaluate the efficacy of intrathecal narcotics pump (ITNP) as an alternative treatment for patients with pain from chronic pancreatitis (CP). ITNP offers the advantages of reversibility, lower total narcotic dose, and the pancreas remaining intact. METHODS Thirteen patients (8 female, 5 male), with mean age 40.6 years (s.d. 9.6 years), who had experienced intractable upper abdominal pain from CP were reviewed. Each patient had multiple other failed treatment modalities, including partial pancreatic resection (n = 6). They were offered ITNP after a successful intraspinal opioid trial. Etiologies of CP included idiopathy (n = 3), cystic fibrosis (n = 2), alcohol (n = 2), and pancreas divisum (n = 6). RESULTS The median duration of severe, intractable pain prior to ITNP was 6 years (2-22 years). The median follow-up time after ITNP was 29 months (range, 7-94 months). The ITNP was in situ for a mean duration of 29 months (range, 0.5-94 months). Seven patients had pump exchange or removal for various reasons; improvement of pain at month 53 (n = 1), meningitis (n = 1), meningitis with subsequent replacement (n = 1), pump failure at month 31, 68, 79, and 84 (n = 4). There were no deaths. The mean pain score prior to implantation (score = 8.3, s.d. = 0.9) was significantly higher than 1 year after (score = 2.7, s.d. = 1.9) (P < 0.01) and last follow-up (score = 0.75, s.d. = 2.1) (P < 0.01). The median oral narcotic dose before and 1 year after ITNP were morphine sulfate equivalents 337.5 mg per day (range, 67.5-1,320) and 40 mg per day (range, 0-1,680), respectively (P < 0.01). Two patients were considered failures, as they still require a high dosage of both oral and intrathecal medications to control their pain, despite significant pain-score improvement. One patient who was excluded due to meningitis was also considered a failure. Therefore, the overall success rate of ITNP based on an intention-to-treat analysis was 76.9% (10/13). The major complications of ITNP were central nervous system infection requiring pump removal (n = 1), cerebrospinal fluid leak requiring laminectomy (n = 1), and perispinal abscess with bacterial meningitis requiring pump removal (n = 1). CONCLUSIONS This study shows the many risks and benefits of ITNP. A longer follow-up is awaited; such pumps appear to be one alternative to aggressive surgical intervention. Failed ITNP trials leave other options open. Therapeutic trials directly comparing pancreatectomy, ITNP, and implanted nerve stimulators are of interest.
Collapse
|