Tropical Calcific Pancreatitis Research Articles

Exploring the role of TLK2 mutation in tropical calcific pancreatitis: an in silico and molecular dynamics simulation study

Tropical calcific pancreatitis (TCP) is a juvenile form of non-alcoholic chronic pancreatitis seen exclusively in tropical countries. The disease poses a high risk of complications, including pancreatic diabetes and cancer, leading to significant mortality due to poor diagnosis and ineffective treatments. This study employed whole exome sequencing (WES) of 5 TCP patient samples to identify genetic variants associated with TCP. Advanced computational techniques were used to gain atomic-level insights into disease progression, including microsecond-scale long MD simulations and essential dynamics. In silico virtual screening was performed to identify potential therapeutic compounds targeting the mutant protein using the Asinex and DrugBank compound library. WES analysis predicted several single nucleotide variants (SNVs) associated with TCP, including a novel missense variant (c.T1802A or p.V601E) in the TLK2 gene. Computational analysis revealed that the p.V601E mutation significantly affected the structure of the TLK2 kinase domain and its conformational dynamics, altering the interaction profile between ATP and the binding pocket. These changes could impact TLK2's kinase activity and functions, potentially correlating with TCP progression. Promising lead compounds that selectively bind to the TLK2 mutant protein were identified, offering potential for therapeutic interventions in TCP. These findings hold great potential for future research. Communicated by Ramaswamy H. Sarma

Molecular dynamics study of tropical calcific pancreatitis (TCP) associated calcium-sensing receptor single nucleotide variation.

Tropical Calcific Pancreatitis (TCP) is a chronic non-alcoholic pancreatitis characterised by extensive calcification. The disease usually appears at a younger age and is more common in tropical regions. This disease’s progression can lead to pancreatic diabetes, which can subsequently lead to pancreatic cancer. The CASR gene encodes a calcium-sensing receptor (CaSR), which is a GPCR protein of class C. It is expressed in the islets of Langerhans, the parathyroid gland, and other tissues. It primarily detects small gradients in circulating calcium concentrations and couples this information to intracellular signalling, which helps to regulate PTH (parathyroid hormone) secretion and mineral ion homeostasis. From co-leading insulin release, CaSR modulates ductal HCO3− secretion, Ca2+ concentration, cell-cell communication, β-cell proliferation, and intracellular Ca2+ release. In pancreatic cancer, the CaSR limits cell proliferation. TCP-related four novel missense mutations P163R, I427S, D433H and V477A, found in CaSR extracellular domain (ECD) protein, which were reported in the mutTCPdb Database (https://lms.snu.edu.in/mutTCPDB/index.php). P163R mutation occurs in ligand-binding domain 1 (LBD-1) of the CaSR ECD. To investigate the influence of these variations on protein function and structural activity multiple in-silico prediction techniques such as SIFT, PolyPhen, CADD scores, and other methods have been utilized. A 500 ns molecular dynamic simulation was performed on the CaSR ECD crystal structure and the corresponding mutated models. Furthermore, Principal Component Analysis (PCA) and Essential Dynamics analysis were used to forecast collective motions, thermodynamic stabilities, and the critical subspace crucial to CaSR functions. The results of molecular dynamic simulations showed that the mutations P163R, I427S, D433H, and V477A caused conformational changes and decreased the stability of protein structures. This study also demonstrates the significance of TCP associated mutations. As a result of our findings, we hypothesised that the investigated mutations may have an effect on the protein’s structure and ability to interact with other molecules, which may be related to the protein’s functional impairment.

Post-Operative Complications of Pancreatico Jejunostomy in Patients with Pancreatic Calculi

Background: Pancreatic calculi are a condition characterised by irreversible destruction and fibrosis of the exocrine parenchyma, leading to exocrine pancreatic insufficiency and progressive endocrine failure leading to diabetes. Tropical calcific pancreatitis, an inflammatory condition of the pancreas, is usually associated with the pancreatic duct stones for which lateral pancreatico jejunostomy provides excellent results with acceptable early morbidity and mortality. Objective: To assess the post-operative complications of pancreatico jejunostomy in patients with pancreatic calculi. Methods: This was a descriptive type of prospective study. A total of 26 patients were included in the study between July 2011 to December 2011 in a BSMMU and other private hospitals of Dhaka who underwent lateral pancreatico jejunostomy for pancreatic calculi. Data were collected using a structured questionnaire and presented in tables by number, percentage, mean±SD, median. Results: This study was conducted to find out the efficacy and safety of lateral pancreatico jejunostomy in cases of pancreatic calculi. Highest proportion of the patients (n=26) are in the age group of 30-40 years (13 out of 26 number of patients. The mean age of the patients is 36.74. More than 64% of the patients were male. Female was found in 35% cases. Revealed that 3.84% of the patients were alcoholic. 96.15% of the patients (25 out of 26 patients) were non alcoholic. 30.76% (8 patients out of 26) is associated with gallstone disease.69.23% (18 patients out of 26) is not associated with gallstone disease. Upper abdominal pain was present in 100% patients. Steatorrhoea was present in 15.38% of the patients (4 patients out of 26).Jaundice predominated in 3.85% of the patients (1 patient out of 26). Shows that 34.61% of the patients (9 patients out of 26) developed post-operative morbidity, death occurred in 3.85% (1 patient out of 26). In our study 11.54% of the patients (3 patients out of 26) ............

The Current Concepts and Management of Idiopathic (Tropical) Chronic Pancreatitis

Tropical chronic pancreatitis (TCP) is a special variant of idiopathic chronic pancreatitis that is seen mainly in tropical countries. Although the prevalence of tropical pancreatitis is high in southern India, it is reported from most parts of India. It occurs usually in young people, involves the main pancreatic duct, and results in large ductal calculi with high incidence of diabetes and malignancy. Recent reports suggest that the presentation is changing. The age of onset is older and the disease course seems to be milder. The etiology is not known, but genetic mutations and environmental factors are likely causes. This article is a narrative review of the recent trends in the etiopathogenesis and management of tropical calcific pancreatitis (TCP). Extensive literature search was done from PubMed and Ovid. Article was prepared by reviewing full-text articles and abstracts related to chronic calcific pancreatitis (CCP) and TCP.

Structural, functional and molecular dynamics analysis of cathepsin B gene SNPs associated with tropical calcific pancreatitis, a rare disease of tropics.

Tropical Calcific Pancreatitis (TCP) is a neglected juvenile form of chronic non-alcoholic pancreatitis. Cathepsin B (CTSB), a lysosomal protease involved in the cellular degradation process, has recently been studied as a potential candidate gene in the pathogenesis of TCP. According to the Cathepsin B hypothesis, mutated CTSB can lead to premature intracellular activation of trypsinogen, a key regulatory mechanism in pancreatitis. So far, CTSB mutations have been studied in pancreatitis and neurodegenerative disorders, but little is known about the structural and functional effect of variants in CTSB. In this study, we investigated the effect of single nucleotide variants (SNVs) specifically associated with TCP, using molecular dynamics and simulation algorithms. There were two non-synonymous variants (L26V and S53G) of CTSB, located in the propeptide region. We tried to predict the effect of these variants on structure and function using multiple algorithms: SIFT, Polyphen2, PANTHER, SDM sever, i-Mutant2.0 suite, mCSM algorithm, and Vadar. Further, using databases like miRdbSNP, PolymiRTS, and miRNASNP, two SNPs in the 3′UTR region were predicted to affect the miRNA binding sites. Structural mutated models of nsSNP mutants (L26V and S53G) were prepared by MODELLER v9.15 and evaluated using TM-Align, Verify 3D, ProSA and Ramachandran plot. The 3D mutated structures were simulated using GROMACS 5.0 to predict the impact of these SNPs on protein stability. The results from in silico analysis and molecular dynamics simulations suggested that these variants in the propeptide region of Cathepsin B could lead to structural and functional changes in the protein and thus could be pathogenic. Hence, the structural and functional analysis results have given interim conclusions that these variants can have a deleterious effect in TCP pathogenesis, either uniquely or in combination with other mutations. Thus, it could be extrapolated that Cathepsin B gene can be screened in samples from all TCP patients in future, to decipher the distribution of variants in patients.

MutTCPdb: a comprehensive database for genomic variants of a tropical country neglected disease-tropical calcific pancreatitis.

Tropical calcific pancreatitis (TCP) is a juvenile, non-alcoholic form of chronic pancreatitis with its exclusive presence in tropical regions associated with the low economic status. TCP initiates in the childhood itself and then proliferates silently. mutTCPdb is a manually curated and comprehensive disease specific single nucleotide variant (SNV) database. Extensive search strategies were employed to create a repository while SNV information was collected from published articles. Several existing databases such as the dbSNP, Uniprot, miRTarBase2.0, HGNC, PFAM, KEGG, PROSITE, MINT, BIOGRID 3.4 and Ensemble Genome Browser 87 were queried to collect information specific to the gene. mutTCPdb is running on the XAMPP web server with MYSQL database in the backend for data storage and management. Currently, the mutTCPdb enlists 100 variants of all 11 genes identified in TCP, out of which 45 are non-synonymous (missense, nonsense, deletions and insertions), 46 are present in non-coding regions (UTRs, promoter region and introns) and 9 are synonymous variants. The database is highly curated for disease-specific gene variants and provides complete information on function, transcript information, pathways, interactions, miRNAs and PubMed references along with remarks. It is an informative portal for clinicians and researchers for a better understanding of the disease, as it may help in identifying novel targets and diagnostic markers, hence, can be a source to improve the strategies for TCP management.Database URL: http://lms.snu.edu.in/mutTCPDB/index.php

Diagnosis and Management of Intraductal Papillary Mucinous Neoplasm of the Pancreas Where Tropical Calcific Pancreatitis Is Prevalent

Diagnosis and Management of Intraductal Papillary Mucinous Neoplasm of the Pancreas Where Tropical Calcific Pancreatitis Is Prevalent

Submitted, Not Presented: Clinical Vignettes/Case Reports - Biliary/Pancreas.

Tropical Calcific Pancreatitis (TCP) is a type of chronic calcific non-alcoholic pancreatitis. It is similar to non-alcoholic chronic pancreatitis, is commonly seen in the second and third decades of life, mostly in the developing countries of the tropical world. It is associated with the formation of calculi in the large ducts, ductal dilatation, and significant fibrosis with a high probability of developing diabetes mellitus. Epidemiologic studies have shown that these patients have an increased lifetime risk of developing pancreatic carcinoma compared to both healthy controls and patients with chronic pancreatitis of differing etiology. The etiology of TCP remains uncertain, with the current consensus suggesting a role for genetics as well as possible toxicity from consuming large amounts of cassava, a tuber (Manihot esculenta). We report the case of a forty four year old male from the Dominican Republic diagnosed with TCP during a recent admission to our hospital. His first episode of Acute Pancreatitis was when he was twenty years old. At that time he lived in the Dominican Republic. He moved to New York approximately twenty years ago; this inpatient admission was his fourth for pancreatitis. He denies consuming alcohol and has no family history of pancreatitis. Causes of acute pancreatitis, such as trauma, autoimmune diseases, scorpion sting, steroid use, infection, hyperlipidemia, hypercalcemia, drug use, and gall stones were excluded by history, by imaging as well as through laboratory studies. Computed tomography of the abdomen done this admission and in 2002, show multiple calcifications in the pancreas. A genetic study was done and he was found to have no variations in the SPINK1 gene. As of submission of this report, he has not developed any complications such as pancreatic necrosis, pancreatic pseudocyst or diabetes mellitus and remains healthy. This is a case of a rare entity in the United States. While this condition is uncommon, the increased lifetime risk of pancreatic carcinoma makes an accurate diagnosis of TCP in patients from the developing tropics vital in preventing morbidity and mortality.

Association Analysis of PRSS1-PRSS2 and CLDN2-MORC4 Variants in Nonalcoholic Chronic Pancreatitis Using Tropical Calcific Pancreatitis as Model.

Association of PRSS1-PRSS2 (rs10273639) and CLDN2-MORC4 (rs12688220 and rs7057398) variants with alcohol-related chronic pancreatitis (CP) is established but with nonalcoholic CP is unclear. We addressed this inconsistency using tropical calcific pancreatitis (TCP) as model. We sequenced 5'-UTR of PRSS1 and genotyped CLDN2-MORC4 variants in 555 patients with TCP and 801 controls and performed association analysis. Gene-gene interaction between PRSS1 and CLDN2-MORC4 variants and with p.Asn34Ser SPINK1 and p.Leu26Val CTSB was also evaluated. We observed significant association of rs10273639/rs4726576 in PRSS1-PRSS2 (odds ratio [OR] = 0.72; P = 3.50 × 10) and CLDN2-MORC4 variants, rs12688220 (OR = 1.54; P = 1.22 × 10) and rs7057398 (OR = 1.50; P = 1.22 × 10) with TCP. Patients carrying p.Asn34Ser SPINK1 were significantly younger than those with rs4726576 risk genotype (30.0 vs 38.0 years; P = 0.015) and those carrying both were even younger (22.0 years; P = 0.001). Presence of risk allele at rs12688220 in patients carrying p.Asn34Ser SPINK1 delayed the age of onset (32.0 vs 24.0 years; P = 0.013). Our study establishes strong association of PRSS1-PRSS2 and CLDN2-MORC4 variants with TCP and thus with nonalcoholic CP. These variants independently interact with p.Asn34Ser SPINK1 and influence the age of onset in TCP. However, latter results need to be replicated in other cohorts.

A Case of Chronic Calcific Nonalcoholic Pancreatitis.

Tropical Calcific Pancreatitis (TCP) is a type of chronic calcific nonalcoholic pancreatitis. Similar to nonalcoholic chronic pancreatitis, it presents in the second and third decades of life; however this type is reported mostly in the developing tropical and subtropical countries. It is associated with the formation of pancreatic calculi and a high probability of developing insulin-dependent diabetes mellitus. Epidemiologic studies have shown that these patients have an increased risk of developing pancreatic carcinoma. The etiology of TCP remains uncertain, with the current consensus suggesting genetics as well as possible toxicity from consuming large amounts of cassava, a tuber. Definite diagnosis of TCP requires younger age of onset, history of malnutrition, and presence of diabetes mellitus along with extensive pancreatic calcification and ductal calculi. When patients meet most but not all of these conditions the term Idiopathic Chronic Pancreatitis (ICP) is used. This is a case of a 44-year-old man who presented with most features seen in TCP, and however, was diagnosed with ICP.

Polymorphism of Alcohol Metabolizing Gene ADH3 Predisposes to Development of Alcoholic Pancreatitis in North Indian Population.

Background and aim: Genetic factors regulating alcohol metabolism could predispose in developing alcoholic pancreatitis (ACP). Studies revealed that alcohol could be metabolized by both ways, oxidative and non-oxidative. The main oxidative pathway includes alcohol dehydrogenase (ADH), aldehyde dehydrogenase (ALDH), and cytochrome P450 enzyme. We investigated the association of polymorphisms in these enzymes with the alcoholic pancreatitis in the north Indian population.Method: Patients with alcoholic pancreatitis (ACP; n = 72), tropical calcific pancreatitis (TCP; n = 75), alcoholic controls (AC; n = 40), and healthy controls (HC; n = 100) were included in the study. Blood samples were collected from the subjects in EDTA coated vials. DNA was extracted and genotyping for ADH3, ALDH2, and CYP2E1 was done by PCR-RFLP (polymerase chain reaction—restriction fragment length polymorphism). The products were analyzed by gel electrophoresis.Result: The frequency distribution of ADH3*1/*1 genotype was significantly higher in ACP group (59.7%) compared with TCP (38.7%), HC (42%), and AC (37.5%) and was found to be associated with increased risk of alcoholic pancreatitis. There was no statistically significant difference between the frequency distribution of ADH3*1/*1, ADH3*1/*2, and ADH3*2/*2 genotypes between TCP and HC or healthy alcoholics. ALDH2 gene was monomorphic in our population, and the frequencies for CYP2E1 intron 6 Dra I polymorphism were comparable in all the four groups.Conclusion: This study shows that carriers of ADH3*1/*1 individuals consuming alcohol are at higher risk for alcoholic pancreatitis than those with other genotypes such as ADH3*1/*2 and ADH3*2/*2.

English

Chronic calcific pancreatitis is a result of chronic inflammation of the pancreas which results in irreversible damage. There are two varieties of chronic calcific pancreatitis (CCP) which is 1. Alcoholic calcific pancreatitis, 2. Tropical calcific pancreatitis, Alcoholic calcific pancreatitis is invariably related to the consumption of alcohol. CCP is a special form of chronic pancreatitis that tends to calcify and is associated with pancreatic lithiasis. Pancreatic lithiasis refers to true calculi in the duct system of the pancreas. Calculi can be due to calcification of the parenchyma. The term tropical calcific pancreatitis refers to the disease which occurs in children and young adults. In contrastACP is commonly seen in adults, in developing countries of the sub-tropics. In India, TCP is commonly seen in Kerala and Tamil Nadu. In the study conducted by Pipali DH et al1, chronic calcific pancreatitis in Western Maharashtra, the mean age of presentation of TCP was 32, and the peak age of presentation among males is 31 to 35, and among females is 16 to 20 years. There was a predominance of males, with a male to female ratio of about 4:1. The patients usually present with symptoms of abdominal pain, steatorrhoea and diabetes. When diabetes is present the condition is called fibrocalcinous pancreatic diabetes. The cause of TCP remains obscure, however susceptibility mutations in the gene encoding serene protease inhibitor Kazal Type-1 (SPINK1) has been identified. METHODS: We did a retrospective analysis of 25 proven cases of chronic calcific pancreatitis, of which 21 turned out to be of alcoholic etiology, 4 cases showed radiological features of tropical calcific pancreatitis. The study was conducted in the Department of Radio diagnosis Sree Gokulam College, Trivandrum, for a period of two years, from January 2012, to December 2013. The patients were referred mainly from the departments of Gastroenterology, and gastro surgery, with clinical features and history corresponding to CCP. RESULTS: The retrospective analysis over a two year period of patients diagnosed as chronic calcific pancreatitis showed that 18 cases were of alcoholic etiology and 6 cases had features of tropical calcific pancreatitis ACP was exclusively seen in male patients, and the TCP group had 2 male and 4 female patients, of which 3 cases had mass lesions which on biopsy were proven to be adenocarcinoma. CONCLUSION: The predominant feature of alcoholic calcific pancreatitis is that small and speckled calculi with mild dilatation of the ducts are seen. Also it is almost exclusive in males in the fourth and fifth decades. The main feature of TCP is that there will be marked fatty replacement of the gland with significant duct dilation and large, dense calculi. Our conclusions also were corroborated with the study by Chari Set al2.

Genetic and phenotypic heterogeneity in tropical calcific pancreatitis.

Tropical calcific pancreatitis (TCP) is a form of chronic non-alcoholic pancreatitis initially reported in the developing parts of the tropical world. The clinical phenotype of TCP has undergone marked changes since its first description in 1968. The disease is now seen in relatively older people with less severe symptoms. In addition, there are varying reports on the proportion of cases presenting with imaging abnormalities like calcification, ductal dilation, and glandular atrophy. Significant progress has also been made in understanding the etiopathology of TCP. The role of malnutrition and cassava toxicity in its pathogenesis is disproven and few studies have focused on the role of micronutrient deficiency and oxidative stress in the etiopathogenesis of TCP. Emerging evidence support an important role for genetic risk factors in TCP. Several studies have shown that, rather than mutations in trypsinogens, variants in serine protease inhibitor kazal type 1, cathepsin B, chymotrypsin C, cystic fibrosis transmembrane regulator, and carboxypeptidase A1, predict risk of TCP. These studies also provided evidence of mutational heterogeneity between TCP and chronic pancreatitis in Western populations. The current review summarizes recent advances that have implications in the understanding of the pathophysiology and thus, heterogeneity in genotype-phenotype correlations in TCP.

Double Blind Randomized Control Study of Intramuscular Vitamin D3 Supplementation in Tropical Calcific Pancreatitis

Vitamin D deficiency is prevalent in chronic pancreatitis (CP), but the optimal route and dose of vitamin D supplementation are unknown. We evaluated the relative efficacy of two different doses of intramuscular (i.m.) vitamin D(3) in patients with CP and vitamin D insufficiency. In a double-blind randomized study, 40 patients with tropical calcific pancreatitis with serum 25-hydroxyvitamin D (25OHD) <75 nmol/L (mean 27.0 ± 14.5 nmol/L, <50 nmol/L in 90 %) were divided into three groups. Groups 1 and 2 received 600,000 IU (15,000 μg) and 300,000 IU (7,500 μg) i.m. cholecalciferol, respectively, while group 3 received i.m. saline. All groups received 1 g calcium and 500 IU (12.5 μg) vitamin D(3) orally daily and were studied for 9 months. The primary outcome was the proportion of patients with vitamin D sufficiency (25OHD >75 nmol/L) at 6 months. Vitamin D sufficiency was significantly different in the three groups (85, 29, and 0 % in groups 1, 2, and 3, respectively; p < 0.001). Mean 25OHD remained >75 nmol/L in months 1-6 in group 1 but reached a lower level (50-75 nmol/L) at these time points in group 2. At 6 months, serum alkaline phosphatase decreased significantly only in group 1 (230 ± 73 vs 165 ± 39 IU/L, p = 0.004). No patient in any group developed hypervitaminosis D or hypercalcemia. In conclusion, in patients with CP, a single i.m. injection of 600,000 IU was more effective at achieving vitamin D sufficiency over 6 months compared with 300,000 IU vitamin D(3). (Clinical Trials.gov number NCT00956839).

Predictors of malignancy in chronic calcific pancreatitis with head mass

To prospectively analyse the clinical, biochemical and radiological characteristics of the mass lesions arising in a background of chronic calcific pancreatitis (CCP). Eighty three patients, who presented with chronic pancreatitis (CP) and a mass lesion in the head of pancreas between February 2005 and December 2011, were included in the study. Patients who were identified to have malignancy underwent Whipple's procedure and patients whose investigations were suggestive of a benign lesion underwent Frey's procedure. Student t-test was used to compare the mean values of imaging findings [common bile duct (CBD), main pancreatic duct (MPD) size] and laboratory data [Serum bilirubin, carbohydrate antigen 19-9 (CA 19-9)] between the groups. Receiver operating characteristic curve (ROC curve) analysis was done to calculate the cutoff valves of serum bilirubin, CA 19-9, MPD and CBD size. The sensitivity, specificity, positive predictive valve (PPV) and negative predictive value (NPV) were calculated using these cut off points. Multivariate analysis was performed using logistic regression model. The study included 56 men (67.5%) and 27 women (32.5%). Sixty (72.3%) patients had tropical calcific pancreatitis and 23 (27.7%) had alcohol related CCP. Histologically, it was confirmed that 55 (66.3%) of the 83 patients had an inflammatory head mass and 28 (33.7%) had a malignant head mass. The mean age of individuals with benign inflammatory mass and those with malignant mass was 38.4 years and 45 years respectively. Significant clinical features that predicted a malignant head mass in CP were presence of a head mass in CCP of tropics, old age, jaundice, sudden worsening abdominal pain, gastric outlet obstruction and significant weight loss (P ≤ 0.05). The ROC curve analysis showed a cut off value of 5.8 mg/dL for serum bilirubin, 127 U/mL for CA 19-9, 11.5 mm for MPD size and 14.5 mm for CBD size. Elevated Serum bilirubin and CA 19-9, and dilated MPD and CBD were useful in predicting malignancy in patients with CCP and head mass.

Fibrocalculous pancreatic diabetes in a young Ugandan patient, a rare form of secondary diabetes

BackgroundFibrocalculous pancreatic diabetes is an infrequent type of secondary diabetes due to chronic tropical non alcoholic calcific pancreatitis. It has been widely described exclusively in developing tropical countries. A diagnosis is made basing on the presence of abdominal pain, presence of pancreatic calcifications, steatorrhoea, and diabetes mellitus.Case presentationWe report a case of a 20 year old Ugandan female patient who presented with features of chronic tropical calcific pancreatitis complicated by diabetes mellitus, oedematous malnutrition and micronutrient deficiencies.ConclusionThis case report demonstrates that fibrocalculous pancreatic diabetes still exists in developing countries like Uganda. Clinicians in such settings should possess a high clinical suspicion of fibrocalculous pancreatic diabetes especially in presence of malnutrition. Challenges of management of such patients in resource limited settings are comprehensively discussed in the review of literature.

Pancreatic diabetes: an Indian perspective

Tropical calcific pancreatitis (TCP) and fibrocalculous pancreatic diabetes (FCPD) are unique forms of non-alcoholic pancreatitis and diabetes found almost exclusively in the tropics. Such patients can be erroneously labelled as having type 1 diabetes. A diagnosis of FCPD has potential implications in treatment, prediction of disease progression and complications. There are several characteristic features including young age of onset, progressive disease, non-ketotic diabetes, pancreatic calculi on imaging and a high risk of pancreatic cancer. Hyperglycaemia is usually severe and requires insulin, although ketoacidosis is a rare occurrence. Long term follow-up is necessary as microvascular complications have been reported. Macrovascular complications are less common due to a multitude of factors. The aetiology of TCP/FCPD is not clear but potential mechanisms include malnutrition, cyanogen toxicity, genetic factors, oxidant stress and micronutrient deficiency.

Stellate cell activation in tropical calcific pancreatitis compared to alcoholic pancreatitis, adenocarcinoma of pancreas and normal pancreas.

Pancreatic stellate cell (PSC) is known to be the source of fibrosis in pancreatic pathology of various etiologies. However, there is no published data on activation of PSCs in tropical calcific pancreatitis.The present study was undertaken to estimate the proportion of activated stellate cells, in a semi-quantitative manner, in normal pancreas and pancreatic fibrosis due to, tropical calcific pancreatitis, alcoholic chronic pancreatitis and pancreatic adenocarcinoma.Surgically resected specimen from patients with tropical calcific pancreatitis (n=22), alcoholic chronic pancreatitis (n=16), adenocarcinoma of pancreas (n=20) and normal pancreas (n=20) were included.Expression of CD34, and alpha-smooth muscle actin (α-SMA) was assessed by immunohistochemistry. Morphometry was performed by a point counting procedure and CD34 positive areas were excluded from α-SMA positive areas for estimating activated PSCs.The one-way ANOVA and the Tukey multiple comparison test were used to compare the proportion of activated stellate cells among the four categories.In all the disease conditions studied, namely, tropical calcific pancreatitis (16.7±14.5%, mean±SD), alcoholic chronic pancreatitis (13.6±12.4%) and pancreatic adenocarcinoma (22.8±14.4%), there was highly significant (P&lt;0.001) increased percentage of activated PSCs compared to normal pancreas (-0.9±6.4%). Proportion of activated PSCs in tropical calcific pancreatitis was similar to that in cases of alcoholic chronic pancreatitis and pancreatic adenocarcinoma. Such activation is documented for the first time in tropical calcific pancreatitis while it is known for the other causes.The present study suggests that a final common pathway of PSC activation leads to fibrogenesis in tropical calcific pancreatitis just as in other pancreatic pathologies.

Comprehensive screening of chymotrypsin C (CTRC) gene in tropical calcific pancreatitis identifies novel variants

ObjectiveIn a previous study, the authors have shown that rather than variants in trypsinogen gene(s), mutations in pancreatic secretory trypsin inhibitor (encoded by SPINK1) and cathepsin B (CTSB) are associated...

Tropical Calcific Pancreatitis

Tropical Calcific Pancreatitis