Dasatinib as a Potential Targeted Therapy for Chronic Pancreatitis: A Narrative Review of Macrophage-PSC Interactions

Resection vs Drainage in Treatment of Chronic Pancreatitis: Long-term Results of a Randomized Trial

Resection Versus Drainage in Treatment of Chronic Pancreatitis

criteria for chronic pancreatitis currently used in Japan were proposed by the Japan Pancreas Society (JPS) in 1995 (JPS Criteria 1995),5,6 with a small revision to include magnetic resonance cholangiopancreatography fi ndings in 2001 (JPS Criteria 2001).7,8 The fi rst Marseilles symposium of 1963 classifi ed pancreatitis into four main groups: (1) acute pancreatitis, (2) relapsing acute pancreatitis with clinical biological restitution of the gland, (3) chronic relapsing pancreatitis with acute exacerbation, and (4) chronic pancreatitis with anatomical and/or functional residual damage to the gland.9 The defi nition of chronic pancreatitis is based on the persistence of lesions. The Cambridge classifi cation of 1983 provided a grading and severity system using imaging tests.3,10 The second Marseilles symposium of 19842 clinically characterized chronic pancreatitis as recurrent or persisting abdominal pain along with pancreatic insuffi ciency indicated by steatorrhea or diabetes, and morphologically characterized it as irregular sclerosis with destruction and permanent loss of exocrine parenchyma and varying degrees of dilatation of the duct system. The most recent Marseilles–Rome classifi cation of 19884 classifi ed chronic pancreatitis into three groups; (1) chronic obstructive pancreatitis; (2) chronic calcifying pancreatitis, which is characterized by the presence of intraductal protein precipitates or plugs and calcifi ed precipitates (calculi or stones); and (3) chronic infl ammatory pancreatitis, which is characterized by the loss of exocrine parenchyma replaced by a dense fi brosis infi ltrated by mononuclear cells. Despite these international expert meetings in the past 40 years, there is no consensus on the classifi cation of chronic pancreatitis because many data on the diagnosis and treatment of chronic pancreatitis from different centers are hard to compare, except those data on patients with advanced chronic pancreatitis. The JPS Criteria of 1995 and 2001 classifi ed chronic pancreatitis into (1) defi nite, (2) probable, and (3) possible chronic pancreatitis.11 The criteria can be applied

Chronic pancreatitis is an inflammatory condition of the pancreas characterized by atrophy, fibrosis, and loss of function. Due to a lack of designated pharmaceutical agents, treatment of canine chronic pancreatitis is usually limited to supportive care. There are reports from Japan about the use of a protease inhibitor, camostat mesilate, for the treatment of chronic pancreatitis in humans, but no controlled studies about the efficacy of camostat mesilate for the treatment of chronic pancreatitis in dogs are available. Therefore, the primary goals of this study were to investigate the efficacy of camostat mesilate in dogs with suspected chronic pancreatitis as well as assess its effect on acinar cell damage by measuring serum concentrations of canine pancreas lipase immunoreactivity (cPLI). Also, the effect of the compound on systemic inflammation was quantified by measurement of serum concentrations of canine C-reactive protein and S100A12. Finally, the effect of camostat mesilate on fibrosis was assessed by measurement of serum concentrations of transforming growth factor (TGF)-β1. Thirty-one dogs with suspected chronic pancreatitis based on clinical signs and repeated measurements of an increased cPLI concentration above the cutoff value for the diagnosis of pancreatitis (≥ 400 μg/L) received a dose of 4 or 8mg/kg camostat mesilate q 8 h (12 or 24 mg/kg q 24 h) over a period of 26 ± 5 days. The evaluation of follow-up questionnaires from referring veterinarians and owners suggested improvement in quality of life in some patients. Only mild side effects were observed. Dogs given a daily camostat mesilate dose of 24 mg/kg/d orally showed a statistically significant decrease in serum cPLI concentrations between pre-treatment (median: 847 μg/L; range: 414 to 2,024 μg/L) and post-treatment (median: 520; range: 193 to 2,580 μg/L; n=19; p=0.016), indicating attenuation of acinar cell damage. Anti-inflammatory effects were comprised of a significant decrease of serum S100A12 concentrations in dogs treated with 12 mg/kg/d camostat mesilate between pre-treatment (median: 160 μg/L; range: 52 to 1327 μg/L) and post-treatment (median: 88 μg/L; range: 43 to 449 μg/L; n=11; p=0.0010). Serum cobalamin concentrations differed significantly between pre-treatment (mean: 868 ng/L; SD: ± 108ng/L) and post-treatment (mean: 695 ng/L; SD: ± 223 ng/L) concentrations in the 12 mg/kg/d group (n=12; p=0.0363) and also between pre-treatment (mean: 749 ng/L; SD: ± 229 ng/L) and post-treatment (mean: 641 ng/L; SD: ± 252 ng/L) concentrations in the 24 mg/kg/d group (n=19; p=0.045). However, no statistically significant changes in TGF-β concentrations, C-reactive protein, parameters of serum biochemistry, or complete blood counts were observed with treatment. This study would suggest a potentially beneficial role of camostat mesilate in dogs with chronic pancreatitis; however, case-control studies are needed to confirm these findings.%%%%Charakteristische Merkmale der chronischen Bauchspeicheldrusenentzundung sind Atrophie, Fibrose und…

An Atypical Complication of Chronic Pancreatitis

Management of Chronic Pancreatitis

Individualizing Therapy for Chronic Pancreatitis

Chronic pancreatitis remains a debilitating disease with few definitive options for treatment. The purpose of this study was to evaluate the benefit of pancreaticoduodenectomy in the treatment of chronic pancreatitis. The results were evaluated by standard descriptive statistics. In a retrospective study, we reviewed the patients at a single institution undergoing pancreaticoduodenectomy between 1994 and 1997 for complications of chronic pancreatitis. Patients were evaluated for preoperative indication for surgery and perioperative morbidity and mortality, as well as long-term results. Thirty-two patients underwent pancreaticoduodenectomy for chronic pancreatitis; 56 per cent (18) underwent pylorus-preserving and 44 per cent (14) underwent classic pancreaticoduodenectomy. The mean age of these patients was 56+/-14.7 years (range, 23-79). All patients underwent preoperative CT scan and endoscopic retrograde cholangiopancreatography. The preoperative indication for surgery in 81 per cent (26) of these patients was intractable pain in the setting of a nondilated pancreatic duct. The other 19 per cent were treated for biliary/pancreatic duct stricture and pancreatic head fibrosis (mass suspicious of malignancy). Fifty-three per cent of the patients had a history of previous abdominal surgery. There were no perioperative deaths. The mean postoperative stay was 12.2+/-7.4 days. The postoperative morbidity rate was 31 per cent (10), consisting of 25 per cent with delayed gastric emptying, 3 per cent with pneumonia, and 3 per cent with wound infections. There was no occurrence of pancreatic fistulas. With a mean follow-up of 40 months (range, 10-52 months), 85 per cent reported a significant improvement in pain with 71 per cent being pain free and not requiring narcotics. Twenty per cent developed new-onset diabetes. The overall event survival rate at 5 years was 97 per cent. Thus, in a selected group of patients with severe chronic pancreatitis, resection of the head of the pancreas achieved relief of symptoms and was a safe and effective treatment for chronic pancreatitis.

In the past two decades our knowledge of the pathophysiology and surgical treatment options in chronic pancreatitis have improved substantially. Surgical treatment in chronic pancreatitis has evolved from radical to organ-preserving procedures. The classic Whipple resection is no longer indicated in chronic pancreatitis, and operations like the duodenum-preserving pancreatic head resection and the pylorus-preserving Whipple have replaced it as surgical standards. These procedures allow the preservation of exocrine and endocrine pancreatic function, provide pain relief in up to 90% of patients, and contribute to an improvement in the quality of life.

Controversies in clinical pancreatology: autoimmune pancreatitis: does it exist?

Background: Epidemiological data regarding the regional differences in chronic pancreatitis (CP) from the mainland of China is lacking. We aimed to gather and combine the information concerning the regional distribution, diagnosis and treatment of CP, in addition to the risk factors associated with pancreatic cancer (PaCa) and death from published articles. Methods: Case articles on CP published in three English and four Chinese databases from January 1979 to December 2018 were analysed. Findings: A total of 4,452 cases articles (containing 161,243 CP cases) were included. Almost all relevant departments of 1,557 hospitals participated in the writing of CP articles and approximately 67.2% of hospitals wrote only one article. The etiologies, symptoms, treatments, and number of cases with PaCa varied from region to region. Surgical treatment was more common in underdeveloped areas. Endoscopic therapy was mainly concentrated in developed areas and was also associated with non-alcoholic CP. PaCa detected during hospitalization was mainly related to jaundice (r = 0.35, P = 0.000), pain (r = 0.31, P = 0.000), diabetes (r = 0.20, P = 0.000), biliary diseases (r = 0.36, P = 0.000), alcoholic CP (r = 0.30, P = 0.000), conservative treatment (r = 0.37, P = 0.000) and surgical treatment (r = 0.21, P = 0.000). PaCa detected during follow-up was primarily associated with idiopathic CP (r = 0.26, P = 0.000), alcoholic CP (r = 0.23, P = 0.000), endoscopy therapy (r = 0.3, P = 0.000) and surgical treatment (r = 0.24, P = 0.000). Death during hospitalization was only related to surgery. Interpretation: Many regions have gradually formed their own unique characteristics in terms of the diagnosis and treatment of CP. However, the level of diagnosis and treatment of CP in many areas still needs to be improved. The problem of uneven distribution of medical resources needs to be resolved. Funding Statement: None. Declaration of Interests: The authors declare that there are no competing interests associated with the manuscript.

Chronic pancreatitis is a long-term illness leading to hospital admissions and readmission. This disease is often caused by heavy alcohol consumption and smoking. Patients with chronic pancreatitis suffer from acute or chronic pain episodes, recurrent pancreatitis, and complications, such as pseudocysts, biliary duct strictures, and pancreatic duct fistulas. Pancreatic duct strictures and stones may increase intraductal pressure and cause pain. Endoscopic therapy is aiming at decompressing the pressure and relieving the pain, most commonly with pancreatic duct stents and pancreatic duct stone retrieval. Early surgery is another option to treat the pain. In addition, endotherapy has been successful in treating complications related to chronic pancreatitis. The therapy should be individually chosen in a multidisciplinary meeting. Endoscopic therapy and surgery as treatment options for chronic pancreatitis are discussed in this review.

Background/Aims: Chronic pancreatitis is an inflammatory disease of the pancreas characterized by progressive tissue destruction and fibrogenesis. The development of chronic pancreatitis is associated with immune cell dysregulation. Currently, the specific and effective treatment of chronic pancreatitis remains absent. Methods: By using an L-arginine induced chronic pancreatitis mouse model, we tested the therapeutic potential of hydrogen, a strong hydroxyl radicals scavenger, in the chronic pancreatitis model. Tissue inflammation, damage and fibrosis were analyzed on HE, TUNEL, MPO, and sirius staining. Pancreas levels of MDA content, SOD activity, TNF-α , IL-10 cytokine expression and serum amylase and lipase activity were determined by ELISA and absorbance assay. Apoptosis, T cells subtype proportion and intracellular level of reactive oxygen species (ROS) were analyzed by flow cytometry. Tregs adoptive transfer and CD25 neutralization were used to validate the role of Tregs in chronic pancreatitis. Results: We found that hydrogen treatment significantly improved multiple symptoms of chronic pancreatitis. The number of Tregs was reduced in chronic pancreatitis mice, while hydrogen treatment restored the Treg loss by L-arginine administrations. Depletion of Tregs abolished the protective effect of hydrogen treatment in chronic pancreatitis. In vitro study showed that hydrogen blocked ROS generation in Tregs and promoted Tregs survival. Conclusion: Hydrogen treatment showed reliable benefits in controlling the severity of chronic pancreatitis. Our study supported that hydrogen could be used as a novel treatment in chronic pancreatitis patient in the future.

European evidence-based guidelines for the treatment and management of chronic pancreatitis (CP) have been made available following the harmonizing diagnosis and treatment of CP across Europe (HaPanEU) initiative by the United European Gastroenterology (UEG). The aim of this study was to evaluate adherence to the guideline recommendations in the management of patients with pancreatic exocrine insufficiency (PEI) at Karolinska University Hospital in Stockholm. UEG guideline recommendations were evaluated and categorized into 55 different quality indicators (QIs). Data from a retrospective cohort of CP patients being treated at Karolinska University Hospital were evaluated with regard to overall adherence as well as adherence to specific QIs. A total number of 118 patients out of 956 patients diagnosed with CP were eligible for inclusion with mean overall adherence of 61.9% to the defined QIs. A significant difference in mean overall adherence was shown between patients diagnosed with CP prior to 1 January 2016 and following 1 January 2016 (59.3% and 67.7% respectively, p = 0.004), with linear regression analysis also demonstrating improvement correlating to date of diagnosis (p = 0.002). In conclusion, diagnosis and treatment of PEI improved after the HaPanEU guidelines became available and is continuously improving; however, there is room for further improvement.

The 53rd meeting of the European Pancreatic Club (online) took place in Verona (Italy) on June 9–11, 2021. The meeting was attended by 690 delegates from 40 countries. More than 400 oral and poster presentations were presented.
 The results of advances in the diagnosis and treatment of chronic pancreatitis, as well as the crucial research directions, were summarized in a lecture by E. de-Madaria et al. (Italy). The main medical and social characteristics of chronic pancreatitis (CP): chronic disease; often manifests itself in pain, which is often disabling; leads to complications, including pancreatic cancer; diagnosis and treatment are complex. Despite this, the number of randomized controlled trials (RCTs) on CP is significantly less than on acute pancreatitis, and in recent years, the annual number of studies on CP has even decreased. Problems to be solved: we do not have antifibrotic drugs, a “gold standard” for diagnosis, and we do not even have good methods for diagnosing early CP. The main etiological CP options are alcoholic and idiopathic ones. A more detailed analysis showed that toxic CP (alcoholic and smoking-induced) account for 46% of cases of the disease, idiopathic CP — 24%, genetically predisposed CP — 7%, obstructive CP — 7%, autoimmune CP — 2%, CP of other etiology — 12% of cases. We have made progress in the study of autoimmune pancreatitis, however, the frequency of pancreatic cancer due to autoimmune CP, features of the disease in children, increased accuracy of pancreas imaging and the effectiveness of treatment require further study in RCTs.
 Lithotripsy, endoscopy, and surgery are used to treat CP with dilated pancreatic ducts. There were 3 RCTs that showed the advantages of surgical treatment over endoscopic one (long-term pain relief, fewer complications, higher efficiency), but lithotripsy and endoscopy were not compared.
 “Small ducts disease” is treated by the blockade of the solar plexus and/or nn. splanchnici, V-shaped excision of the pancreas, pancreatectomy with autotransplantation of the islets of Langerhans (only in specialized centers). The effectiveness of these techniques requires further study. The main techniques for diagnosing exocrine pancreatic insufficiency (EPI) are: probe (laborious), fecal elastase test (low sensitivity in mild EPI), tests for assessing trophological status (low specificity), breath tests (not available everywhere and laborious).
 Thus, we need an more RCTs (international efforts), definition of early CP; we need to better understand the relationship between genetic and environmental factors, advance in understanding of the autoimmune pancreatitis, and understanding the role of endoscopy and lithotripsy in pain management; it is necessary to develop new techniques of treating pain in the “small ducts disease”; we need easy-to-perform, accurate and widespread tests to diagnose EPI.
 The article analyzes the results of studies on the diagnosis and treatment of pancreatitis, cysts and pancreatic tumors.