A tricky pancreatic stone face to an expanding endoscopic armamentarium: we can lose a battle but not the war

No disponible

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.

Recurrent furunculosis in returning travelers: newly defined entity.

BACKGROUND: Bacterial skin infection is a common dermatologic problem in travelers, which usually resolves without sequela. In contrast, post-travel recurrent furunculosis (PTRF) is a new unique entity of a sequential occurrence of many furuncles seen after returning home from a trip to the Tropics. OBJECTIVE: The objective of this study was to characterize the disease course and possible causes of PTRF. METHODS: A retrospective study was conducted on a group of young, healthy individuals (16 males and 5 females), who presented with PTRF after returning from tropical countries. RESULTS: In all patients, the first furuncle appeared toward the end of the trip and continued for several months after returning home. The average duration of disease was 8.4 months with an average of 4.2 recurrences. Along the disease course, subsequent recurrences became shorter and milder with longer inter-recurrence intervals. Bacterial cultures most commonly grew methicillin-sensitive Staphylococcus aureus (MSSA, 76.5%). Nasal colonization was demonstrated in 47% of patients. There were neither companion travelers nor family members experiencing furuncles. CONCLUSIONS: PTRF should be defined as a clinical entity with prolonged travel to the Tropics being its major risk factor. In the author's opinion, a transient immune change in a subpopulation of travelers ignites a series of recurrent furuncles, resolving upon restoration of normal immunity.

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).

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

OBJECTIVE: In 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 with tropical calcific pancreatitis (TCP). Recently, chymotrypsin C (CTRC) variants that diminish its activity or secretion were found to predict susceptibility to chronic pancreatitis (CP). The authors analysed CTRC variants in a large, ethnically matched case-control TCP cohort. DESIGN: The authors sequenced all eight exons and flanking regions in CTRC in 584 CP patients (497 TCP, 87 idiopathic CP) and 598 normal subjects and analysed the significance of association using χ(2) test. The authors also investigated interaction of CTRC variants with p.N34S SPINK1 and p.L26V CTSB mutations. RESULTS: The authors identified 14 variants in CTRC, of which non-synonymous variants were detected in 71/584 CP patients (12.2%) and 22/598 controls (3.7%; OR 3.62, 95% CI 2.21 to 5.93; p=6.2 × 10(-8)). Rather than the commonly reported p.K247_R254del variant in Caucasians, p.V235I was the most common mutation in Indian CP patients (28/575 (4.9%); OR 7.60, 95% CI 2.52 to 25.71; p=1.01 × 10(-5)). Another pathogenic variant, p.A73T was identified in 3.1% (18/584) patients compared with 0.3% (2/598) in controls (OR=9.48, 95% CI 2.19 to 41.03, p=2.5 × 10(-4)). The authors also observed significant association for the synonymous variant c.180C>T (p.(=)) with CP (OR 2.71, 95% CI 1.79 to 4.12, p=5.3 × 10(-7)). Two novel nonsense mutations, p.G242AfsX9 and p.W113X were also identified exclusively in CP patients. No interaction between CTRC variants and p.N34S SPINK1 or p.L26V CTSB mutations was observed. CONCLUSION: This study on a large cohort of TCP patients provides evidence of allelic heterogeneity and confirms that CTRC variants play a significant role in its pathogenesis.

Some aspects of the etiology and the pathogenesis of chronic pancreatitis.

The development of modern technology and advances in medical science make possible understanding of etiology of chronic pancreatitis. From a century ago, the ethanol is connected to chronic pancreatitis. In the last decades medical science made a big footstep in understanding of so called "idiopathic pancreatitis". Factors as autoimmune disturbances, toxins, gene mutations, geographic characteristics are already known as cornerstones in etiology and pathogenesis of the disease.

Pancreatite crônica hereditária: relato de caso / Chronic hereditary pancreatitis: case report

A pancreatite crônica hereditária é definida como uma doença autossômica dominante rara caracterizada porepisódios recorrentes de pancreatite aguda em dois ou mais membros de várias gerações da família. A maioriados pacientes possui mutações nos genes PRSS1, SPINK1 ou CFTR. Relata-se o caso de uma paciente com um quadro agudo de pancreatite secundário a um processo crônico calcificado subjacente, em que na investigação familiar seis membros já haviamapresentado episódios de pancreatite. A pesquisa das alterações genéticas características não foi possível porlimitações do serviço.

Chronic hereditary pancreatitis is defined as a rare autossomic dominant disease, characterized by recurrentepisodes of acute pancreattis in two or more members of several familiar generations. Most of these patientspresent mutation on genes PRSS1, SPINK1 or CFTR. It’s reported the case of a patient with an acute episodeof pancreatitis secondary to a chronic calcified underlying process, in which six cases of history of previous episodesof pancreatitis were found, through familiar investigation. The screening for genetic alterations was not possibledue to the lack of resources of the heath care service.