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1.
J Gastroenterol Hepatol ; 36(5): 1226-1234, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33000865

RESUMO

BACKGROUND AND AIM: Even though ductal interventions in chronic pancreatitis (CP) are known to improve pain, its impact on diabetes is unclear. In this cohort study, we evaluated the impact of ductal interventions on diabetes in these patients. METHODS: Consecutive patients with CP visiting the pancreas clinic between August 1, 2011, and July 21, 2012, were enrolled and followed until December 2018. Detailed clinical, laboratory, imaging, and treatment data were recorded at enrolment and follow-up. Patients were followed up every 6 months through hospital visit and/or telephonic interview. Risk factors for diabetes were evaluated using logistic regression. The impact of ductal interventions on diabetes was evaluated using Kaplan-Meier survival analyses and Cox proportional hazards. RESULTS: A total of 644 patients were enrolled of which 137 were excluded. Of these, 326 (64.3%) patients had idiopathic CP, and 283 (55.8%) patients underwent ductal intervention. The cumulative incidence of diabetes was 57.9%. Median duration between symptom onset and ductal intervention was similar irrespective of diabetes (2.6 [0.6-6.0] vs 3.0 [1.0-5.5] years; P = 0.69). Alcohol intake and pancreatic ductal calculi were independent risk factors for diabetes (odds ratio [95% confidence interval] of 2.05 (1.18-3.55), P = 0.01, and 2.05 (1.28-3.28), P = 0.003, respectively). Kaplan-Meier analyses revealed that diabetes free interval was significantly longer in patients undergoing ductal interventions, predominantly in those with idiopathic CP with obstructive ductal calculi (hazard ratio [95% confidence interval] 0.39 [0.28-0.55]; P < 0.0001). There were no differences in glycemic status in patients with non-idiopathic CP and those with pre-existing diabetes. CONCLUSION: Early ductal intervention could delay development of diabetes in patients with idiopathic CP with obstructive ductal calculi.


Assuntos
Diabetes Mellitus/etiologia , Diabetes Mellitus/prevenção & controle , Ductos Pancreáticos/cirurgia , Pancreatite Crônica/complicações , Pancreatite Crônica/cirurgia , Adolescente , Adulto , Estudos de Coortes , Diabetes Mellitus/epidemiologia , Drenagem , Endoscopia do Sistema Digestório , Feminino , Seguimentos , Humanos , Incidência , Modelos Logísticos , Masculino , Dor/etiologia , Dor/cirurgia , Fatores de Risco , Fatores de Tempo , Adulto Jovem
2.
Endoscopy ; 52(7): 569-573, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32106321

RESUMO

BACKGROUND: Recent guidelines from the European Society of Gastrointestinal Endoscopy (ESGE) and American Society for Gastrointestinal Endoscopy (ASGE) recommend risk stratification according to liver function test (LFT) and abdominal ultrasound in patients with suspected choledocholithiasis. We evaluated and validated the clinical utility of these new risk stratification criteria for choledocholithiasis. METHODS: We retrospectively analyzed prospectively maintained data of patients with suspected choledocholithiasis between January 2016 and December 2018 in patients undergoing cholecystectomy. Patients with common bile duct stricture, cirrhosis, and portal biliopathy were excluded. After LFT and ultrasound, all patients were stratified according to ESGE and ASGE criteria into high, intermediate, and low likelihood of choledocholithiasis. RESULTS: 1042 patients were analyzed. Using ESGE guidelines, 213 patients (20.4 %) met high likelihood criteria, 637 (61.1 %) met intermediate, and 192 (18.4 %) met low likelihood criteria. Using ASGE guidelines, 230 (22.1 %), 678 (65.1 %), and 134 (12.9 %) met high, intermediate, and low likelihood criteria, respectively. Specificity and positive predictive value (PPV) of ASGE high likelihood criteria were 96.87 % (95 % confidence interval [CI] 95.37 - 97.98) and 89.57 % (95 %CI 85.20 - 92.75) for choledocholithiasis compared with 98.96 % (95 %CI 97.95 - 99.55) and 96.24 % (95 %CI 92.76 - 98.09), respectively, for ESGE criteria. ASGE classified 17 (7.4 %) additional patients as high likelihood compared with ESGE, only one of whom had choledocholithiasis. ASGE classified 58 (8.6 %) additional patients as intermediate, none of whom had choledocholithiasis. CONCLUSION: This study validates the clinical utility of new ESGE and ASGE criteria for predicting choledocholithiasis. ESGE risk stratification appears more specific than ASGE.


Assuntos
Coledocolitíase , Colangiopancreatografia Retrógrada Endoscópica , Colecistectomia , Coledocolitíase/diagnóstico por imagem , Coledocolitíase/cirurgia , Endoscopia Gastrointestinal , Humanos , Estudos Retrospectivos , Estados Unidos
3.
Indian J Gastroenterol ; 38(5): 411-440, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31802441

RESUMO

The Indian Society of Gastroenterology developed this evidence-based practice guideline for management of gastroesophageal reflux disease (GERD) in adults. A modified Delphi process was used to develop this consensus containing 58 statements, which were generated by electronic voting iteration as well as face-to-face meeting and review of the supporting literature primarily from India. These statements include 10 on epidemiology, 8 on clinical presentation, 10 on investigations, 23 on treatment (including medical, endoscopic, and surgical modalities), and 7 on complications of GERD. When the proportion of those who voted either to accept completely or with minor reservation was 80% or higher, the statement was regarded as accepted. The prevalence of GERD in India ranges from 7.6% to 30%, being < 10% in most population studies, and higher in cohort studies. The dietary factors associated with GERD include use of spices and non-vegetarian food. Helicobacter pylori is thought to have a negative relation with GERD; H. pylori negative patients have higher grade of symptoms of GERD and esophagitis. Less than 10% of GERD patients in India have erosive esophagitis. In patients with occasional or mild symptoms, antacids and histamine H2 receptor blockers (H2RAs) may be used, and proton pump inhibitors (PPI) should be used in patients with frequent or severe symptoms. Prokinetics have limited proven role in management of GERD.


Assuntos
Gastroenterologia/normas , Refluxo Gastroesofágico/epidemiologia , Refluxo Gastroesofágico/terapia , Guias de Prática Clínica como Assunto , Adulto , Antiácidos/uso terapêutico , Consenso , Dieta/efeitos adversos , Esofagite/epidemiologia , Esofagite/etiologia , Feminino , Refluxo Gastroesofágico/etiologia , Infecções por Helicobacter/complicações , Helicobacter pylori , Antagonistas dos Receptores H2 da Histamina/uso terapêutico , Humanos , Índia/epidemiologia , Masculino , Prevalência , Inibidores da Bomba de Prótons/uso terapêutico , Sociedades Médicas
4.
Saudi J Med Med Sci ; 6(2): 95-99, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30787828

RESUMO

BACKGROUND: Primary hyperparathyroidism due to parathyroid adenoma presenting with pancreatitis as the initial manifestation is rare. The causal relationship between pancreatitis and primary hyperparathyroidism is debatable. OBJECTIVE: To study the clinical and biochemical profile of patients with parathyroid adenoma-associated pancreatitis as well as the outcome following parathyroidectomy. METHODS: The authors retrospectively studied the clinical and biochemical parameters of patients with acute, recurrent acute and chronic pancreatitis who underwent parathyroidectomy for parathyroid adenoma at Asian Institute of Gastroenterology, Hyderabad, India, between April 2010 and June 2016. RESULTS: Of the total 3962 patients who presented with recurrent acute and chronic pancreatitis, 77 (1.94%) patients had parathyroid adenoma-associated pancreatitis and were included in this study for further analysis. Of these, 41 (53.2%) had recurrent acute pancreatitis and 36 (46.8%) had chronic pancreatitis. Serum calcium (12.4 ± 1.7 mg/dl) and parathyroid hormone levels (367 ± 286.4 pg/ml) were found to be elevated. Left inferior parathyroid adenoma (37.7%) was the most common finding on neck imaging. Patients with chronic pancreatitis had a longer disease duration (3.8 ± 5 years) and more pain episodes (10.7 ± 10.2) than those with recurrent acute pancreatitis (0.62 ± 0.7 years and 2.6 ± 2.7, respectively) (P = 0.0001). In all the patients, following parathyroidectomy, there was a significant decrease in serum calcium (12.4 ± 1.7 mg/dl vs. 9.7 ± 1.9 mg/dl; P = 0.0001) and serum parathyroid hormone levels (367 ± 286.4 pg/ml vs. 116.4 ± 47.1 pg/ml; P = 0.0001) as well as there was a reduction in the number of episodes and severity of pain. CONCLUSIONS: Estimating serum calcium after an episode of unexplained pancreatitis is important and can help minimize delay in diagnosing primary hyperparathyroidism, and possibly prevent the progression of pancreatitis. Parathyroidectomy improves the clinical outcome of primary hyperparathyroidism and prevents further attacks of pancreatitis.

5.
Endoscopy ; 50(4): 358-370, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29169196

RESUMO

BACKGROUND AND STUDY AIM: Peroral endoscopic myotomy (POEM) has emerged as an effective treatment modality for achalasia. Prior treatment may affect the outcomes of subsequent management. In this study, we aimed to compare the safety and efficacy of POEM in treatment-naïve patients vs. those with prior treatment failure (PTF). PATIENTS AND METHODS: The data of consecutive patients with achalasia who underwent POEM at a single tertiary care center from January 2013 to November 2016 were analyzed retrospectively. A comparative analysis was performed between treatment-naïve and PTF cases. Technical and clinical success, adverse events, and operative time for POEM were compared between the two groups. RESULTS: Overall, 502 patients with achalasia underwent POEM during the study period: 260 patients (51.8 %) in the treatment-naïve group and 242 patients (48.2 %) in the PTF group. The mean operative time was significantly longer in the PTF group compared with the treatment-naïve group (74.9 ±â€Š30.6 vs. 67.0 ±â€Š27.1 minutes; P  = 0.002). On multivariate analysis, type of achalasia, dilated esophagus ( > 6 cm), disease duration, prior treatment, occurrence of adverse events, and type of knife used were significant predictors of operative time. Technical success (98.1 % vs. 97.1 %; P = 0.56) and clinical success (92.4 % vs. 92.5 %; P  = 0.95) were comparable in the treatment-naïve and PTF cases, respectively. Occurrence of gas-related events and mucosotomy were similar in both groups. Elevated DeMeester score was found in 17 /53 patients (32.1 %) in the PTF group and in 11 /44 patients (25.0 %) in the treatment-naïve group (P = 0.50). CONCLUSION: POEM is safe and equally effective for treatment-naïve patients and for those in whom prior treatment has failed. POEM should be considered the treatment of choice in patients in whom prior treatment has failed.


Assuntos
Endoscopia Gastrointestinal , Acalasia Esofágica/cirurgia , Miotomia de Heller/métodos , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Dilatação Patológica/complicações , Endoscopia Gastrointestinal/efeitos adversos , Esôfago/patologia , Feminino , Miotomia de Heller/efeitos adversos , Miotomia de Heller/instrumentação , Humanos , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia , Retratamento , Estudos Retrospectivos , Fatores de Tempo , Falha de Tratamento , Adulto Jovem
6.
World J Gastroenterol ; 23(3): 382-405, 2017 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-28210075

RESUMO

Pancreatic stellate cells (PSCs) were identified in the early 1980s, but received much attention after 1998 when the methods to isolate and culture them from murine and human sources were developed. PSCs contribute to a small proportion of all pancreatic cells under physiological condition, but are essential for maintaining the normal pancreatic architecture. Quiescent PSCs are characterized by the presence of vitamin A laden lipid droplets. Upon PSC activation, these perinuclear lipid droplets disappear from the cytosol, attain a myofibroblast like phenotype and expresses the activation marker, alpha smooth muscle actin. PSCs maintain their activated phenotype via an autocrine loop involving different cytokines and contribute to progressive fibrosis in chronic pancreatitis (CP) and pancreatic ductal adenocarcinoma (PDAC). Several pathways (e.g., JAK-STAT, Smad, Wnt signaling, Hedgehog etc.), transcription factors and miRNAs have been implicated in the inflammatory and profibrogenic function of PSCs. The role of PSCs goes much beyond fibrosis/desmoplasia in PDAC. It is now shown that PSCs are involved in significant crosstalk between the pancreatic cancer cells and the cancer stroma. These interactions result in tumour progression, metastasis, tumour hypoxia, immune evasion and drug resistance. This is the rationale for therapeutic preclinical and clinical trials that have targeted PSCs and the cancer stroma.


Assuntos
Carcinoma Ductal Pancreático/fisiopatologia , Pâncreas Exócrino/patologia , Neoplasias Pancreáticas/fisiopatologia , Células Estreladas do Pâncreas/metabolismo , Células Estreladas do Pâncreas/patologia , Pancreatite Crônica/fisiopatologia , Animais , Carcinoma Ductal Pancreático/tratamento farmacológico , Carcinoma Ductal Pancreático/imunologia , Citocinas/metabolismo , Proteínas da Matriz Extracelular/metabolismo , Fibrose , Humanos , MicroRNAs/metabolismo , Invasividade Neoplásica , Pâncreas Exócrino/citologia , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/imunologia , Células Estreladas do Pâncreas/efeitos dos fármacos , Células Estreladas do Pâncreas/imunologia , Pancreatite Crônica/tratamento farmacológico , Pancreatite Crônica/imunologia , Transdução de Sinais , Microambiente Tumoral
7.
J Gastroenterol Hepatol ; 31(9): 1654-62, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26945817

RESUMO

BACKGROUND AND AIM: The aim of this study was to evaluate the effect of antioxidant-pregabalin combination on pain recurrence in patients with chronic calcific pancreatitis. METHODS: In this randomized, double-blind, placebo-controlled trial, chronic calcific pancreatitis patients with pain recurrence following pancreatic ductal clearance of stones received either antioxidant-pregabalin combination or matching placebo for 2 months followed by open-label antioxidants for the next 4 months in both groups. Compliance, daily pain, and adverse events were recorded weekly and at the end of study by a coordinator blinded to treatment status. Primary outcome was pain improvement (visual analog scale and Izbicki score); secondary outcomes were as follows: complete pain resolution, painful days, and adverse events. Number needed-to-treat was calculated. RESULTS: We randomized 42 and 45 patients (mean age 29.3 years) to treatment and placebo arms, respectively. Baseline characteristics, including pain scores, were similar for both groups. No patients received high-potency narcotic. At 2 months, a significant improvement in the treatment arm was observed in percent reduction of visual analog scale (-50 [-80.0; -32.1] vs -29.5 [-64.5; 0]; P = 0.01), Izbicki score (14.5 [0; 21.3] vs 30.0 [11.8; 41.3]; P = 0.001), complete pain resolution (20 [47.6%] vs 12 [26.7%]; P = 0.04), and number of painful days (10.0 [2.0; 16.0] vs 18.0 [7.0; 34.0]; P = 0.01). Needed-to-treat was 4.8. Pain reduction persisted at 6 months in the original treatment group (20.0 [15.0; 28.0] vs 36.0 [20.0; 50.0]; P = 0.006). A total of 33 patients in the treatment arm experienced mild to moderate self-limiting nausea/vomiting and drowsiness, respectively and did not require any change in study protocol. CONCLUSION: Antioxidant-pregabalin combination results in significant relief in pain recurrence after ductal clearance in narcotic naïve patients with chronic calcific pancreatitis.


Assuntos
Analgésicos não Narcóticos/uso terapêutico , Antioxidantes/uso terapêutico , Cálculos/cirurgia , Dor/prevenção & controle , Pancreatite Crônica/cirurgia , Pregabalina/uso terapêutico , Adulto , Cálculos/complicações , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Humanos , Masculino , Dor/etiologia , Medição da Dor/métodos , Pancreatite Crônica/complicações , Qualidade de Vida , Recidiva , Prevenção Secundária/métodos , Resultado do Tratamento , Adulto Jovem
8.
Pancreas ; 45(8): 1153-7, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-26784911

RESUMO

OBJECTIVE: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.


Assuntos
Pancreatite Crônica , Alelos , Calcinose , Claudinas , Predisposição Genética para Doença , Genótipo , Humanos , Mutação , Proteínas Nucleares , Razão de Chances , Tripsina , Inibidor da Tripsina Pancreática de Kazal , Tripsinogênio
9.
Gut ; 62(11): 1602-6, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22580415

RESUMO

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.


Assuntos
Calcinose/genética , Quimotripsina/genética , Mutação , Pancreatite Crônica/congênito , Calcinose/enzimologia , Proteínas de Transporte/genética , Estudos de Casos e Controles , Catepsina B/genética , Predisposição Genética para Doença , Genótipo , Humanos , Pancreatite Crônica/enzimologia , Pancreatite Crônica/genética , Inibidor da Tripsina Pancreática de Kazal
11.
Trop Gastroenterol ; 30(1): 5-10, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19624081

RESUMO

A few years ago a new approach to performing abdominal surgery was presented, i.e. via the natural body orifices using endoscopes. The interest and research in this approach progressed very rapidly, in spite of the initial skepticism. It was initially demonstrated in animal models, then in human beings and has now very nearly become routine practice. This article reviews the development of natural orifice transluminal endoscopic surgery (NOTES), its benefits and the hurdles we have yet to overcome.


Assuntos
Endoscopia/métodos , Cavidade Abdominal/cirurgia , Animais , Endoscopia/educação , Endossonografia/métodos , Humanos , Robótica , Resultado do Tratamento
12.
World J Gastroenterol ; 15(3): 264-9, 2009 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-19140225

RESUMO

Chronic pancreatitis is known to be a heterogeneous disease with varied etiologies. Tropical calcific pancreatitis (TCP) is a severe form of chronic pancreatitis unique to developing countries. With growing evidence of genetic factors contributing to the pathogenesis of TCP, this review is aimed at compiling the available information in this field. We also propose a two hit model to explain the sequence of events in the pathogenesis of TCP.


Assuntos
Calcinose/genética , Pancreatite Crônica/genética , Pancreatite Crônica/patologia , Calcinose/etiologia , Calcinose/patologia , Proteínas de Transporte/genética , Predisposição Genética para Doença , Humanos , Mutação , Pancreatite Crônica/etiologia , Clima Tropical , Tripsina , Inibidor da Tripsina Pancreática de Kazal , Tripsinogênio/genética , Tripsinogênio/metabolismo
13.
Indian J Gastroenterol ; 27(5): 204-6, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-19112192

RESUMO

The worldwide incidence of esophageal carcinoma has been rising rapidly over the past few decades. However, in only 31% of patients the carcinoma is detected early in situ. It is essential to detect the malignancy early and to determine the extent of the disease to ensure the best option for a cure. Recent advances in endoscopic technology, including high-resolution magnification endoscopy, narrow-band imaging and endocytoscopy, have increased detection rates of oesophageal microcarcinomas. We report three cases of esophageal malignancy where the use of newer diagnostic techniques ensured an early diagnosis which led to a modified course of management.


Assuntos
Carcinoma in Situ/diagnóstico , Carcinoma de Células Escamosas/diagnóstico , Endoscopia Gastrointestinal/métodos , Neoplasias Esofágicas/diagnóstico , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
15.
BMC Med Genet ; 9: 80, 2008 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-18706099

RESUMO

BACKGROUND: Tropical calcific pancreatitis (TCP) is a type of chronic pancreatitis unique to developing countries in tropical regions and one of its important features is invariable progression to diabetes, a condition called fibro-calculous pancreatic diabetes (FCPD), but the nature of diabetes in TCP is controversial. We analysed the recently reported type 2 diabetes (T2D) associated polymorphisms in the TCF7L2 gene using a case-control approach, under the hypothesis that TCF7L2 variants should show similar association if diabetes in FCPD is similar to T2D. We also investigated the interaction between the TCF7L2 variants and N34S SPINK1 and L26V CTSB mutations, since they are strong predictors of risk for TCP. METHODS: Two polymorphisms rs7903146 and rs12255372 in the TCF7L2 gene were analyzed by direct sequencing in 478 well-characterized TCP patients and 661 healthy controls of Dravidian and Indo-European ethnicities. Their association with TCP with diabetes (FCPD) and without diabetes was tested in both populations independently using chi-square test. Finally, a meta analysis was performed on all the cases and controls for assessing the overall significance irrespective of ethnicity. We dichotomized the whole cohort based on the presence or absence of N34S SPINK1 and L26V CTSB mutations and further subdivided them into TCP and FCPD patients and compared the distribution of TCF7L2 variants between them. RESULTS: The allelic and genotypic frequencies for both TCF7L2 polymorphisms, did not differ significantly between TCP patients and controls belonging to either of the ethnic groups or taken together. No statistically significant association of the SNPs was observed with TCP or FCPD or between carriers and non-carriers of N34S SPINK1 and L26V CTSB mutations. The minor allele frequency for rs7903146 was different between TCP and FCPD patients carrying the N34S SPINK1 variant but did not reach statistical significance (OR = 1.59, 95% CI = 0.93-2.70, P = 0.09), while, TCF7L2variant showed a statistically significant association between TCP and FCPD patients carrying the 26V allele (OR = 1.69, 95% CI = 1.11-2.56, P = 0.013). CONCLUSION: Type 2 diabetes associated TCF7L2 variants are not associated with diabetes in TCP. Since, TCF7L2 is a major susceptibility gene for T2D, it may be hypothesized that the diabetes in TCP patients may not be similar to T2D. Our data also suggests that co-existence of TCF7L2 variants and the SPINK1 and CTSB mutations, that predict susceptibility to exocrine damage, may interact to determine the onset of diabetes in TCP patients.


Assuntos
Calcinose/genética , Proteínas de Transporte/genética , Catepsina B/genética , Diabetes Mellitus Tipo 2/genética , Pancreatite Crônica/genética , Fatores de Transcrição TCF/genética , Alelos , Calcinose/complicações , Calcinose/etnologia , Estudos de Coortes , Diabetes Mellitus Tipo 2/etnologia , Diabetes Mellitus Tipo 2/etiologia , Etnicidade , Feminino , Frequência do Gene , Predisposição Genética para Doença , Genótipo , Humanos , Índia , Masculino , Mutação , Pancreatite Crônica/complicações , Pancreatite Crônica/etnologia , Polimorfismo de Nucleotídeo Único , Proteína 2 Semelhante ao Fator 7 de Transcrição , Inibidor da Tripsina Pancreática de Kazal
16.
Gastrointest Endosc ; 68(2): 362-5, 2008 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-18534588

RESUMO

BACKGROUND: Endoscopic transmural pseudocyst drainage is a multistep procedure. OBJECTIVE: Our purpose was evaluation of a new device, the transluminal balloon accessotome (TBA) in transmural drainage of pancreatic pseudocysts. DESIGN: Case series. SETTING: Subspecialty tertiary care center. PATIENTS AND INTERVENTIONS: Between September and October 2007, all consecutive patients with symptomatic pancreatic pseudocysts in whom TBA was used for pseudocyst drainage were included. Through a therapeutic duodenoscope, the pseudocyst was punctured with the needle-knife of the TBA at the point of maximal bulge. After the cyst cavity was entered, the needle-knife and the handle of the TBA device were withdrawn and a 0.035-inch guidewire was passed into the cavity. The tract was dilated with the inflatable balloon of the TBA device, and a 10F double-pigtail was inserted. RESULTS: Six patients, all male, median age 35 years, underwent transmural pancreatic pseudocyst drainage with TBA during this period. All procedures were completed successfully. There were no major complications during or after the procedure except for fever in 1 patient, which responded to parenteral antibiotics. At 6-week follow-up, the pseudocyst cavity had completely collapsed, and stents could be extracted in all patients. LIMITATIONS: Single-center experience, small sample size. CONCLUSIONS: TBA is a safe, useful, and easy-to-use device for transmural drainage of pancreatic pseudocysts.


Assuntos
Cateterismo/instrumentação , Drenagem/instrumentação , Endoscopia do Sistema Digestório/métodos , Pseudocisto Pancreático/cirurgia , Adolescente , Adulto , Estudos de Coortes , Endossonografia/métodos , Desenho de Equipamento , Segurança de Equipamentos , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Minimamente Invasivos/instrumentação , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Pseudocisto Pancreático/diagnóstico por imagem , Medição de Risco , Resultado do Tratamento
17.
World J Gastroenterol ; 13(44): 5938-43, 2007 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-17990360

RESUMO

AIM: To investigate the allelic and haplotypic association of reg1alpha gene with tropical calcific pancreatitis (TCP). Since TCP is known to have a variable genetic basis, we investigated the interaction between mutations in the susceptibility genes, SPINK1 and CTSB with reg1alpha polymorphisms. METHODS: We analyzed the polymorphisms in the reg1alpha gene by sequencing the gene including its promoter region in 195 TCP patients and 150 ethnically matched controls, compared their allele and haplotype frequencies, and their association with the pathogenesis and pancreaticolithiasis in TCP and fibro-calculous pancreatic diabetes. RESULTS: We found 8 reported and 2 novel polymo-rphisms including an insertion-deletion polymorphism in the promoter region of reg1alpha. None of the 5'UTR variants altered any known transcription factor binding sites, neither did any show a statistically significant association with TCP. No association with any reg1alpha variants was observed on dichotomization of patients based on their N34S SPINK1 or L26V CTSB status. CONCLUSION: Polymorphisms in reg1alpha gene, including the regulatory variants singly or in combination with the known mutations in SPINK1 and/or CTSB genes, are not associated with tropical calcific pancreatitis.


Assuntos
Testes Genéticos , Litostatina/genética , Pancreatite/genética , Calcinose , Proteínas de Transporte/genética , Estudos de Casos e Controles , Catepsina B/genética , Feminino , Frequência do Gene/genética , Haplótipos/genética , Humanos , Masculino , Mutação/genética , Pâncreas/patologia , Polimorfismo Genético/genética , Medicina Tropical , Inibidor da Tripsina Pancreática de Kazal
19.
BMC Med Genet ; 7: 73, 2006 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-17010210

RESUMO

BACKGROUND: Peutz-Jeghers syndrome (PJS) is a rare multi-organ cancer syndrome and understanding its genetic basis may help comprehend the molecular mechanism of familial cancer. A number of germ line mutations in the STK11 gene, encoding a serine threonine kinase have been reported in these patients. However, STK11 mutations do not explain all PJS cases. An earlier study reported absence of STK11 mutations in two Indian families and suggested another potential locus on 19q13.4 in one of them. METHODS: We sequenced the promoter and the coding region including the splice-site junctions of the STK11 gene in 16 affected members from ten well-characterized Indian PJS families with a positive family history. RESULTS: We did not observe any of the reported mutations in the STK11 gene in the index patients from these families. We identified a novel pathogenic mutation (c.790_793 delTTTG) in the STK11 gene in one index patient (10%) and three members of his family. The mutation resulted in a frame-shift leading to premature termination of the STK11 protein at 286th codon, disruption of kinase domain and complete loss of C-terminal regulatory domain. Based on these results, we could offer predictive genetic testing, prenatal diagnosis and genetic counselling to other members of the family. CONCLUSION: Ours is the first study reporting the presence of STK11 mutation in Indian PJS patients. It also suggests that reported mutations in the STK11 gene are not responsible for the disease and novel mutations also do not account for many Indian PJS patients. Large-scale genomic deletions in the STK11 gene or another locus may be associated with the PJS phenotype in India and are worth future investigation.


Assuntos
Síndrome de Peutz-Jeghers/genética , Proteínas Serina-Treonina Quinases/genética , Quinases Proteína-Quinases Ativadas por AMP , Adulto , Sequência de Bases , Códon sem Sentido , Endoscopia Gastrointestinal , Família , Feminino , Mutação da Fase de Leitura , Deleção de Genes , Humanos , Índia , Lactente , Masculino , Pessoa de Meia-Idade , Síndrome de Peutz-Jeghers/sangue , Fenótipo , Reação em Cadeia da Polimerase , Pólipos/genética , Pólipos/patologia , Pólipos/cirurgia , Regiões Promotoras Genéticas , Proteínas Serina-Treonina Quinases/química , Estrutura Terciária de Proteína
20.
Gastrointest Endosc Clin N Am ; 13(4): 765-73, x-xi, 2003 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-14986797

RESUMO

Biliary parasitosis is one of the common causes of biliary obstruction in developing countries and can often be confused with stone disease. With increased worldwide travel and immigration, these conditions are not limited to the developing countries alone. Ascariasis, hydatid liver disease, clonorchiasis, and fascioliasis are the commonly encountered parasitic infestations of the biliary tract usually presenting with biliary colic or cholangitis. Endoscopy has an important role in the diagnosis and emergent management of these conditions and in elective endoscopic therapy of associated complications. Endoscopic sphincterotomy and bile ductal clearance, along with pharmacotherapy, are the mainstays of treatment.


Assuntos
Doenças Biliares/terapia , Endoscopia do Sistema Digestório/métodos , Helmintíase/terapia , Doenças Biliares/diagnóstico , Colangiopancreatografia Retrógrada Endoscópica , Helmintíase/diagnóstico , Humanos
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