Chronic pancreatitis:Pain and computed tomography/magnetic resonance imaging findings

Chronic pancreatitis(CP)is a fibroinflammatory disease characterized by irreversible destruction of pancreatic tissue.With the development of the disease,it may lead to exocrine and/or endocrine insufficiency.CP is one of the common diseases that cause abdominal pain,which will not get permanent spontaneous relief as the disease evolves.The American College of Gastroenterology clinical guidelines recommend computed tomography or magnetic resonance imaging as the first-line examination for the diagnosis of CP.CP common imaging findings include pancreatic atrophy,irregular dilatation of the pancreatic duct,calcification of pancreatic parenchyma,pancreatic duct stones,etc.In clinical practice,whether any correlations between CP-induced abdominal pain patterns(no pain/constant/intermittent pain)and corresponding imaging findings present are not well known.Therefore,this review aims to comprehensively sort out and analyze the relevant information by collecting lots of literature on this field,so as to construct a cross-bridge between the clinical manifestations and imaging manifestations of CP patients.Also,it provides an imaging basis and foundation for the classification and diagnosis of abdominal pain types in clinical CP patients.

Chronic pancreatitis as a driving factor for pancreatic cancer:An epidemiological understanding

The retrospective study by Lew et al(2022)examined the rising hospitalization rates for chronic pancreatitis(CP)and its association with pancreatic ductal adenocarcinoma(PDAC),revealing significant ethno-racial disparities and risk factors.Overweight black men aged 40-59 years and white men over 40 years with higher incomes showed an elevated risk of PDAC among CP patients.The study,which included 14.2 million admissions from 2016-2017,found that 2.6%of adult patients were diagnosed with CP,with white males being the majority.Multivariate regression analysis identified men,black individuals,those aged 40-59 years,and individuals with a body mass index(BMI)between 25 and 29.9 as having an increased risk for CP.Moreover,0.78%of CP patients also had PDAC,with older age and BMI being significant risk factors for developing PDAC in CP patients.The study also highlighted disparities in healthcare access and utilization among different socioeconomic and ethno-racial groups,which may impact the risk and outcomes of CP and PDAC.

Pain in chronic pancreatitis:What can we do today?

The aim of this study is to illustrate the complexity of pain management in chronic pancreatitis(CP).In this context,pain represents the most common and debilitating symptom,and it deeply affects patient’s quality of life.Multiple rating scales(unidimensional,bidimensional and multidimensional)have been proposed to quantify CP pain.However,it represents the result of complex mechanisms,involving genetic,neuropathic and neurogenic factors.Considering all these aspects,the treatment should be discussed in a multidisciplinary setting and it should be approached in a stepwise manner.First,a lifestyle change is recommended and nonsteroidal anti-inflammatory drugs represent the gold standard among medical treatments for CP patients.The second step,after medical approach,is endoscopic therapy,especially for complicated CP.In case of failure,tailored surgery represents the third step and decompressive or resection procedures can be chosen.In conclusion,CP pain’s management is challenging considering all these complex aspects and the lack of international protocols.

Dietary Green Tea Extract and Antioxidants Improve Insulin Secretory Functions of Pancreatic β-Cells in Mild and Severe Experimental Rodent Model of Chronic Pancreatitis

Chronic pancreatitis (CP) is a progressive inflammatory disorder of the pancreas. It is predominantly idiopathic (with an unknown cause) in India and mostly due to alcohol in the West. Diabetes that occur secondary to chronic pancreatitis (T3c Diabetes) is often brittle, and is difficult to attain normoglycemia with conventional treatment requiring multiple doses of insulin. Mild and severe model of CP was induced in mice by repeated intraperitoneal injections of cerulein and L-arginine respectively with an intent to study islet dysfunction and develop therapeutic strategy in animal models of CP. Dietary intervention of epigallocatechin-3-gallate (EGCG) was tested in both the models of CP for its beneficial effects on insulin secretory functions. Pancreata collected upon euthanasia were used to study alterations in the morphology of pancreatic parenchyma and inflammation by staining with H&E and fibrotic changes by Masson’s trichrome and picrosirius staining. Insulin secretory functions of islets were evaluated to test the efficacy of the dietary intervention on β-cell functions. Intraperitoneal glucose tolerance test was performed to monitor the glucose homeostasis before and after the dietary intervention. Both the models resulted in CP with dispersed acini, inflammation and fibrosis. The loss of acini and extent of fibrosis was more in L-arginine model. 2-fold improvement in glucose-stimulated insulin secretory functions of islets was observed with 0.5% EGCG dietary intervention in cerulein model of CP and 1.6-fold in L-arginine model of CP. A further improvement in insulin secretion by 3.2-fold was observed with additional dietary supplements like N-acetyl cysteine, curcumin in combination with EGCG. Our results thus demonstrate and highlight the therapeutic potential of dietary green tea (EGCG) supplementation in reversing islet dysfunction and improving glucose homeostasis in experimental chronic pancreatitis in mice.

Dietary intake in patients with chronic pancreatitis:A systematic review and meta-analysis

BACKGROUND A progressive reduction in the secretion of pancreatic enzymes in patients with chronic pancreatitis(CP)results in malabsorption and ultimate malnutrition.However,the pathogenesis of malnutrition is multifactorial and other factors such as chronic inflammation,alcohol excess and poor dietary intake all contribute.Patients may restrict their dietary intake due to poor appetite or to avoid gastrointestinal symptoms and abdominal pain.Whilst up to half of patients with chronic pancreatitis are reportedly malnourished,the dietary intake of patients with CP is relatively understudied and has not been systematically reviewed to date.AIM To perform a systematic review and meta-analysis of the dietary intakes of patients with CP compared to healthy controls,and to compare the dietary intake of patients with alcohol-related CP and non-alcohol-related CP.METHODS A systematic literature search was performed using EMBASE,MEDLINE,and Cochrane review on studies published between 1946 and August 30th,2019.Adult subjects with a diagnosis of CP who had undergone dietary assessment were included in the systematic review(qualitative analysis).Studies on patients with other pancreatic diseases or who had undergone pancreatic surgery were not included.Studies comparing the dietary intake of patients with CP to that of healthy controls were included in the meta-analysis(quantitative analysis).Metaanalysis was performed using Review Manager 5.3.Newcastle Ottawa Scale(NOS)was used to assess quality of studies.RESULTS Of 6715 studies retrieved in the search,23 were eligible for qualitative analysis while 12 were eligible for quantitative analysis.In the meta-analysis,the total energy(calorie)intake of patients with CP was similar to that of healthy controls[mean difference(MD):171.3;95%confidence interval(CI):-226.01,568.5;P=0.4],however patients with CP consumed significantly fewer non-alcohol calories than controls[MD:-694.1;95%CI:-1256.1,(-132.1);P=0.02].CP patients consumed more protein,but carbohydrate and fat intakes did not differ significantly.Those with alcohol-related CP consumed more mean(standard deviation)calories than CP patients with a non-alcohol aetiology[2642(1090)kcal and 1372(394)kcal,respectively,P=0.046],as well as more protein,fat,but not carbohydrate.CONCLUSION Although patients with CP had similar calorie intake to controls,studies that analysed the contribution of alcohol to energy intake showed that patients with CP consumed fewer non-alcohol calories than healthy controls.A high calorie intake,made up to a large degree by alcohol,may in part contribute to poor nutritional status in CP.

Follow-up of patients with pseudotumoral chronic pancreatitis: Outcome and surveillance

AIM: To follow up patients with pseudotumoral chronic pancreatitis (PCP) to assess their outcome and identify an optimal surveillance interval.

Pancreatic carcinoma coexisting with chronic pancreatitis versus tumor-forming pancreatitis:Diagnostic utility of the time-signal intensity curve from dynamic contrast-enhanced MR imaging

AIM: To evaluate the ability of the time-signal intensity curve (TIC) of the pancreas obtained from dynamic contrast-enhanced magnetic resonance imaging (MRI) for differentiation of focal pancreatic masses, especially pancreatic carcinoma coexisting with chronic pancreatitis and tumor-forming pancreatitis. METHODS: Forty-eight consecutive patients who underwent surgery for a focal pancreatic mass, including pancreatic ductal carcinoma (n = 33), tumor-forming pancreatitis (n = 8), and islet cell tumor (n = 7), were reviewed. Five pancreatic carcinomas coexisted with longstanding chronic pancreatitis. The pancreatic TICs were obtained from the pancreatic mass and the pancreatic parenchyma both proximal and distal to the mass lesion in each patient, prior to surgery, and were classified into 4 types according to the time to a peak: 25 s and 1, 2, and 3 min after the bolus injection of contrast material, namely, type-Ⅰ, Ⅱ, Ⅲ, and Ⅳ, respectively, and were then compared to the corresponding histological pancreatic conditions. RESULTS: Pancreatic carcinomas demonstrated type-Ⅲ (n = 13) or Ⅳ (n = 20) TIC. Tumor-forming pancreatitis showed type-Ⅱ (n = 5) or Ⅲ (n = 3) TIC. All islet cell tumors revealed type-Ⅰ. The type-Ⅳ TIC was only recognized in pancreatic carcinoma, and the TIC of carcinoma always depicted the slowest rise to a peak among the 3 pancreatic TICs measured in each patient, even in patients with chronic pancreatitis.CONCLUSION: Pancreatic TIC from dynamic MRI provides reliable information for distinguishing pancreatic carcinoma from other pancreatic masses, and may enable us to avoid unnecessary pancreatic surgery and delays in making a correct diagnosis of pancreatic carcinoma, especially, in patients with longstanding chronic pancreatitis.

Evaluation of clinical relevance of examining K-ras, p16 and p53 mutations along with allelic losses at 9p and 18q in EUS-guided fine needle aspiration samples of patients with chronic pancreatitis and pancreatic cancer

AIM： To establish an optimum combination of molecular markers resulting in best overall diagnostic sensitivity and specificity for evaluation of suspicious pancreatic mass. METHODS： Endoscopic ultrasound （EUS）-guided fine needle aspiration cytology （FNA） was performed on 101 consecutive patients （63 males, 38 females, 60 ± 12 years; 81 with subsequently diagnosed pancreatic cancer, 20 with chronic pancreatitis） with focal pancreatic mass. Samples were evaluated on-site by an experienced cytopathologist. DNA was extracted from Giemsa stained cells selected by laser microdissection and the presence of K-ras, p53 and p16 somatic mutations was tested by cycling-gradient capillary electrophoresis （CGCE） and single-strand conformation polymorphism （SSCP） techniques. In addition, allelic losses of tumor suppressor genes p16 （INK4, CDKN2A） and DPC4 （MADH4, SMAD4） were detected by monitoring the loss of heterozygosity （LOH） at 9p and 18q, respectively. RESULTS： Sensitivity and specificity of EUS-guided FNA were 75% and 85%, positive and negative predictive value reached 100%. The remaining 26% samples were assigned as inconclusive. Testing of molecular markers revealed sensitivity and specificity of 70% and 100% for K-ras mutations （P 〈 0.001）, 24% and 90% for p53 mutations （NS）, 13% and 100% for p16 mutations （NS）, 85% and 64% for aUelic losses at 9p （P 〈 0.001） and 78% and 57% for allelic losses at 18q （P 〈 0.05）. When tests for different molecular markers were combined, the best results were obtained with K-ras ＋ LOH at 9p （92% and 64%, P 〈 0.001）, K-ras ＋ LOH at 18q （92% and 57%, P 〈 0.001）, and K-ras ＋ LOH 9q ＋ LOH 18q （96% and 43%, P 〈 0.001）. When the molecular markers were used as complements to FNA cytology to evaluate inconclusive samples only, the overall sensitivity of cancer detection was 100% in all patients enrolled in the study. CONCLUSION： EUS-guided FNA cytology combined with screening of K-ras mutations and allelic losses of tumor suppressors p16 and DPC4 represents a very sensitive approach in screening for pancreatic malignancy. Molecular markers may find its use particularly in cases where FNA cytology has been inconclusive.

Difficulty with diagnosis of malignant pancreatic neoplasms coexisting with chronic pancreatitis

Chronic pancreatitis is a relatively common disease. We encountered two different cases of belatedly demonstrated pancreatic carcinoma featuring underlying chronic pancreatitis. The first case was one that was highly suspected as that of a malignancy based upon imaging study, but unfortunately, it could not be confirmed by intra-operative cytology at that time. Following this, the surgeon elected to perform only conservative bypass surgery for obstructive biliary complication. Peritoneal carcinomatosis was later noted and the patient finally died. The second case, a malignant mucinous neoplasm,was falsely diagnosed as a pseudocyst, based upon the lesion's sonographic appearance and associated elevated serum amylase levels. After suffering repeated hemoptysis,the patient was found to exhibit lung metastasis and peritoneal seeding. We reviewed some of the literature,including those studies discussing chronic pancreatitis predisposing to a malignant change. These two case analyses illustrate clearly that the diagnosis for such conditions, which is simply based upon imagery or pathological considerations may end up being one of a mistaken malignancy. Some of our suggestions for the treatment of such malignancies as revealed herein include,total pancreatomy for univocal mass lesion, and needle aspiration of lesion-contained tissue for amylase, CA199and CEA levels for a suspicious cystic pancreatic mass.

Diagnostic criteria for autoimmune chronic pancreatitis revisited

Autoimmune chronic pancreatitis （AIP） is increasingly being recognized worldwidely, as knowledge of this entity builds up. Above all, AIP is a very attractive disease to clinicians in terms of its dramatic response to the oral steroid therapy in contrast to ordinary chronic pancreatitis. Although many characteristic findings of AIP have been described, definite diagnostic criteria have not been fully established. In the year 2002, the Japan Pancreas Society published the diagnostic criteria of AIP and many clinicians around the world use these criteria for the diagnosis of AIP. The diagnostic criteria proposed by the Japan Pancreas Society, however, are not completely satisfactory and some groups use their own criteria in reporting AIP. This review discusses several potential limitations of current diagnostic criteria for this increasingly recognized condition. The manuscript is organized to emphasize the need for convening a consensus to develop improved diagnostic criteria.

Endoscopic ultrasound in chronic pancreatitis: Where are we now?

Endoscopic ultrasonography (EUS) is well suited for assessment of the pancreas due to its high resolution and the proximity of the transducer to the pancreas, avoiding air in the gut. Evaluation of chronic pancreatitis (CP) was an early target for EUS, initially just for diagnosis but later for therapeutic purposes. The diagnosis of CP is still accomplished using the standard scoring based on nine criteria, all considered to be of equal value. For diagnosis of any CP, at least three or four criteria must be fulf illed, but for diagnosis of severe CP at least six criteria are necessary. The Rosemont classif ication, more restrictive, aims to standardize the criteria and assigns different values to different features, but requires further validation. EUS-f ine needle aspiration (EUS-FNA) is less advisable for diagnosis of diffuse CP due to its potential side effects. Elastography and contrast-enhanced EUS are orientation in differentiating a focal pancreatic mass in a parenchyma with features of CP, but they cannot replace EUS-FNA. The usefulness of EUS-guided celiac block for painful CP is still being debated with regard to the best technique and the indications. EUS-guided drainage of pseudocysts is preferred in non-bulging pseudocysts or in the presence of portal hypertension. EUS-guided drainage of the main pancreatic duct should be reserved for cases in which endoscopic retrograde cholangiopancreatography has failed owing to difficult cannulation of the papilla or diff icult endotherapy. It should be performed only by highly skilled endoscopists, due to the high rate of complications.

Chronic pancreatitis,pancreatic adenocarcinoma and the black box in-between

Pancreatic cancer is a challenging disease for patients,doctors and researchers who for decades have searched for a cure for this deadly malignancy.Although existing mouse models of pancreatic cancer have shed light on the mecha-nistic basis of the neoplastic conversion of the pancreas,their impact in terms of offering new diagnostics and therapeu-tic modalities remains limited.Chronic pancreatitis is an inflammatory disease of the pancreas that is associated with a gradual damage of the organ and an increased risk of developing neoplastic lesions.In this review,we propose that detailed studies of chronic inflammatory processes in the pancreas will provide insights into the evolution of pancreatic cancer.This information may prove useful in the design of effective therapeutic strategies to battle the disease.

Diagnosis of mild chronic pancreatitis (Cambridge classification):Comparative study using secretin injection-magnetic resonance cholangiopancreatography and endoscopic retrograde pancreatography

AIM： To investigate the usefulness of secretin injection- MRCP for the diagnosis of mild chronic pancreatitis.METHODS： Sixteen patients having mild chronic pancreatitis according to the Cambridge classification and 12 control subjects with no abnormal findings on the pancreatogram were examined for the diagnostic accuracy of secretin injection-MRCP regarding abnormal branch pancreatic ducts associated with mild chronic pancreatitis （Cambridge Classification）, using endoscopic retrograde cholangiopancreatography （ERCP） for comparison.RESULTS： The sensitivity and specificity for abnormal branch pancreatic ducts determined by two reviewers were respectively 55%-63% and 75%-83% in the head, 57%-64% and 82%-83% in the body, and 44%-44% and 72%-76% in the tail of the pancreas. The sensitivity and specificity for mild chronic pancreatitis were 56%-63% and 92%-92%, respectively. Interobserver agreement （K statistics） concerning the diagnosis of an abnormal branch pancreatic duct and of mild chronic pancreatitis was good to excellent.CONCLUSION： Secretin injection-MRCP might be useful for the diagnosis of mild chronic pancreatitis.

Management of chronic pancreatitis complicated with a bleeding pseudoaneurysm

Chronic pancreatitis is an ongoing disease characterized by persistent inflammation of pancreatic tissues. With disease progression, patients with chronic pancreatitis may develop troublesome complications in addition to exocrine and endocrine pancreatic functional loss. Among them, a pseudoaneurysm, mainly induced by digestive enzyme erosion of vessels in proximity to the pancreas, is a rare and life-threatening complication if bleeding of the pseudoaneurysm occurs. At present, no prospective randomized trials have investigated the therapeutic strategy for this rare but critical situation. The role of arterial embolization, the timing of surgical intervention and even surgical procedures are still controversial. In this review, we suggest that dynamic abdominal computed tomography and angiography should be performed first to localize the bleeders and to evaluate the associated complications such as pseudocyst formation, followed by arterial embolization to stop the bleeding and to achieve early stabilization of the patient’s condition. With advances and improvements in endoscopic devices and techniques, therapeutic endoscopy for pancreatic pseudocysts is technically feasible, safe and effective. Surgical intervention is recommended for a bleeding pseudoaneurysm in patients with chronic pancreatitis who are in an unstable condition, for those in whom arterial embolization of the bleeding pseudoaneurysm fails, and when endoscopic management of the pseudocyst is unsuccessful. If a bleeding pseudoaneurysm is located over the tail of the pancreas, resection is a preferential procedure, whereas if the lesion is situated over the head or body of the pancreas, relatively conservative surgical procedures are recommended.

Role of MMP-2 and MMP-9 and their natural inhibitors in liver fibrosis, chronic pancreatitis and non-specific inflammatory bowel diseases

BACKGROUND： There is a growing evidence that matrix metalloproteinase （MMP）-2 and MMP-9 （gelatinases） play an important role in the pathogenesis of numerous disorders, especially with inflammatory etiology and extracellular matrix （ECM） remodeling. Despite the fact that gelatinases involve in liver cirrhosis is provided in the literature, their role in the pathogenesis of chronic pancreatitis and non-specific inflammatory bowel diseases is still under investigation. DATA SOURCES： We carried out a PubMed search of Englishlanguage articles relevant to the involvement of gelatinases in the pathogenesis of liver fibrosis, pancreatitis, and non-specific inflammatory bowel diseases. RESULTS： The decreased activity of gelatinases, especially MMP-2, is related to the development of liver fibrosis, probably due to the decrease of capability for ECM remodeling. Similar situation can be found in chronic pancreatitis; however, reports on this matter are rare. The presence of non-specific inflammatory bowel diseases results in MMP-9 activity elevation. CONCLUSION： The fluctuation of gelatinases activity during liver fibrosis, chronic pancreatitis and non-specific inflammatory bowel diseases is observed, but the exact role of these enzymes demands further studies.

Pancreatic duct stones in patients with chronic pancreatitis:surgical outcomes

BACKGROUND: Pancreatic duct stone (PDS) is a common complication of chronic pancreatitis. Surgery is a common therapeutic option for PDS. In this study we assessed the surgical procedures for PDS in patients with chronic pancreatitis at our hospital. METHOD: Between January 2004 and September 2009, medical records from 35 patients diagnosed with PDS associated with chronic pancreatitis were retrospectively reviewed and the patients were followed up for up to 67 months. RESULTS: The 35 patients underwent ultrasonography, computed tomography, or both, with an overall accuracy rate of 85.7%. Of these patients, 31 underwent the modified Puestow procedure, 2 underwent the Whipple procedure, 1 underwent simple stone removal by duct incision, and 1 underwent pancreatic abscess drainage. Of the 35 patients, 28 were followed up for 4-67 months. There was no postoperative death before discharge or during follow-up. After the modified Puestow procedure, abdominal pain was reduced in patients with complete or incomplete stone clearance (P>0.05). Steatorrhea and diabetes mellitus developed in several patients during a long-term follow-up. CONCLUSIONS: Surgery, especially the modified Puestow procedure, is effective and safe for patients with PDS associated with chronic pancreatitis. Decompression of intraductal pressure rather than complete clearance of all stones predicts postoperative outcome.

Effect of NCPB and VSPL on pain and quality of life in chronic pancreatitis patients

AIM: To compare the effects of neurolytic celiac plexus block (NCPB) and videothoracoscopic splanchnicectomy (VSPL) on pain and quality of life of chronic pancreatitis (CP) patients.METHODS: Forty-eight small duct CP patients were treated invasively with NCPB (n = 30) or VSPL (n = 18) in two non-randomized, prospective, case-controlled protocols due to chronic pain syndrome, and compared to a control group who were treated conservatively (n = 32). Visual analog scales were used to assess pain and opioid consumption rate was evaluated. In addition, the quality of life was measured using QLQ C-30 for NCPB and FACIT for VSPL.Although both questionnaires covered similar problems,they could not be compared directly one with another.Therefore, the studies were compared by meta-analysis methodology.RESULTS: Both procedures resulted in a significant positive effect on pain of CP patients. Opioids were withdrawn totally in 47.0% of NCPB and 36.4% of VSPL patients,and reduced in 53.0% and 45.4% of the respective patient groups. No reduction in opioid usage was observed in the control group. In addition, fatigue and emotional well-being showed improvements. Finally, NCPB demonstrated stronger positive effects on social support, which might possibly be attributed to earlier presentation of patients treated with NCPB.CONCLUSION: Both invasive pain treatment methods are effective in CP patients with chronic pain.

Study on chronic pancreatitis and pancreatic cancer using MRS and pancreatic juice samples

AIM:To investigate the markers of pancreatic diseases and provide basic data and experimental methods for the diagnosis of pancreatic diseases.METHODS:There were 15 patients in the present study,among whom 10 had pancreatic cancer and 5,chronic pancreatitis.In all patients,pancreatic cancer or chronic pancreatitis was located on the head of the p-a-ncrea-s.Pa-thology da-ta-of a-ll p-a-tients wa-s confirmed by biopsy and surgery.Among the 10 patients with pancreatic cancer,3 people had a medical history of longterm alcohol consumption.Of 5 patients with chronic pancreatitis,4 men suffered from alcoholic chronic pancreatitis.Pancreatic juice samples were obtained from patients by endoscopic retrograde cholangiopancreatography.Magnetic resonance spectroscopyn was performed on an 11.7-T scanner (Bruker DRX-500) using Call-Purcell-Meiboom-Gill pulse sequences.The parameters were as follows:spectral width,15 KHz;time domain,64 K;number of scans,512;and acquisition time,2.128 s.RESULTS:The main component of pancreatic juice included leucine,iso-leucine,valine,lactate,alanine,acetate,aspartate,lysine,glycine,threonine,tyrosine,histidine,tryptophan,and phenylalanine.On performing 1D 1H and 2D total correlation spectroscopy,we found a triplet peak at the chemical shift of 1.19 ppm,which only appeared in the spectra of pancreatic juice obtained from patients with alcoholic chronic pancreatitis.This triplet peak was considered the resonance of the methyl of ethoxy group,which may be associated with the metabolism of alcohol in the pancreas.CONCLUSION:The triplet peak,at the chemical shift of 1.19 ppm is likely to be the characteristic metabolite of alcoholic chronic pancreatitis.

Pain management in chronic pancreatitis

Abdominal pain is a major clinical problem in patients with chronic pancreatitis. The cause of pain is usually multifactorial with a complex interplay of factors contributing to a varying degree to the pain in an individual patient and, therefore, a rigid standardized approach for pain control tends to lead to suboptimal results. Pain management usually proceeds in a stepwise approach beginning with general lifestyle recommendations. Low fat diet, alcohol and smoking cessation are encouraged. Analgesics alone are needed in almost all patients. Maneuvers aimed at suppression of pancreatic secretion are routinely tried. Patients with ongoing symptoms may be candidates for more invasive options such as endoscopic therapy, and resective or drainage surgery. The role of pain modifying agents (antidepressants, gabapentin, peregabalin), celiac plexus block, antioxidants, octreotide and total pancreatectomy with islet cell auto transplantation remains to be determined.

Association between calcium sensing receptor gene polymorphisms and chronic pancreatitis in a US population:Role of serine protease inhibitor Kazal 1type and alcohol

AIM： To test the hypothesis that calcium sensing receptor （CASR） polymorphisms are associated with chronic pancreatitis （CP）, and to determine whether serine protease inhibitor Kazal 1type （SPINK1） N34S or alcohol are necessary co-factors in its etiology. METHODS： Initially, 115 subjects with pancreatitis and 66 controls were evaluated, of whom 57 patients and 21 controls were predetermined to carry the high-risk SPINK1 N34S polymorphism. We sequenced CASR gene exons 2, 3, 4, 5 and 7, areas containing the majority of reported polymorphisms and novel mutations. Based on the initial results, we added 223 patients and 239 controls to analyze three common nonsynonymous single nucleotide polymorphisms （SNPs） in exon 7 （A986S, R990G, and Q1011E）. RESULTS： The CASR exon 7 R990G polyrnorphism was significantly associated with CP （OR, 2.01; 95% CI, 1.12-3.59; P = 0.015）. The association between CASR R990G and CP was stronger in subjects who reported moderate or heavy alcohol consumption （OR, 3.12; 95% CI, 1.14-9.13; P = 0.018）. There was no association between the various CASR genotypes and SPINK1 N34S in pancreatitis. None of the novel CASR polymorphisms reported from Germany and India was detected. CONCLUSION： Our United States-based study confirmed an association of CASR and CP and for the first time demonstrated that CASR R990G is a significant risk factor for CP. We also conclude that the risk of CP with CASR R990G is increased in subjects with moderate to heavy alcohol consumption.