Endoscopic Management of Pancreatic Fluid Collections: An Update

Pancreatic fluid collections (PFCs) are a frequent complication of acute pancreatitis. PFCs have been categorized according to their content and duration after an episode of pancreatitis. Acute collections (4 weeks) can be usually managed conservatively. Late collections including walled off necrosis (WON) and pancreatic pseudocysts (PP) have a well-defined wall. Consequently, it is easier and safer to drain these collections when required. The most common indication to drain PFCs is infection and the available means of drainage include surgical, endoscopic, and percutaneous. Open surgical interventions carry a high risk of morbidity and mortality. Therefore, in the current era, a step up approach is preferred to minimize morbidity over the more aggressive surgical treatments. Endoscopic step-up approach is effective and favored over minimally invasive surgical or percutaneous drainage due to reduced risk of organ failure and external pancreatic fistula. However, the approach to PFCs should be individualized for optimal outcomes. A small subgroup of patients does not respond to endotherapy or percutaneous interventions and requires open surgical debridement. Similarly, not all PFCs are amenable to endoscopic drainage and demand alternative modalities like percutaneous or minimally invasive surgical drainage

Endoscopic Management of Combined Biliary and Duodenal Obstruction

Combined obstruction of the bile duct and duodenum is a common occurrence in periampullary malignancies. The obstruction of gastric outlet or duodenum can follow, occur simultaneously, or precede biliary obstruction. The prognosis in patients with combined obstruction is particularly poor. Therefore, minimally invasive palliation is preferred in these patients to avoid morbidity associated with surgery. Endoscopic palliation is preferred to surgical bypass due to similar efficacy, less morbidity, and shorter hospital stay. The success of endoscopic palliation depends on the type of bilioduodenal stenosis and the presence of previously placed duodenal metal stents. Biliary cannulation is difficult in type II bilioduodenal strictures where the duodenal stenosis is located at the level of the papilla. Consequentially, technical and clinical success is lower in these patients than in those with type I and III bilioduodenal strictures. However, in cases with failure of endoscopic retrograde cholangiopancreatography, with the introduction of endoscopic ultrasound for biliary drainage, the success of endoscopic bilioduodenal bypass is likely to increase further. The safety and efficacy of endoscopic ultrasound-guided drainage has been documented in multiple studies. With the development of dedicated accessories and standardization of drainage techniques, the role of endoscopic ultrasound is likely to expand further in cases with double obstruction

Role of Small Bowel Endoscopy in Diagnosis and Management of Inflammatory Bowel Disease: Current Perspective

The evaluation of small bowel in inflammatory bowel disease (IBD) is mainly performed in cases with newly diagnosed or suspected Crohn’s disease (CD). The available modalities for small bowel evaluation include radiological imaging (barium meal follow through, magnetic resonance enteroclysis, computed tomography enteroclysis) and small bowel endoscopy also known as enteroscopy. The main advantage of small bowel endoscopy over radiological imaging is that it allows for obtaining biopsy specimen required for histological confirmation of the diagnosis. Various endoscopic modalities for endoscopic evaluation of small bowel include push enteroscopy and device assisted enteroscopy (DAE). Push enteroscopy allows only limited evaluation of proximal small bowel. Therefore, DAE is generally preferred over push enteroscopy for small bowel evaluation. DAE includes single balloon enteroscopy, double balloon enteroscopy, and spiral enteroscopy. The available literature suggests that there is no significant difference in the diagnostic yield among the available DAE devices. Therefore, the choice of DAE is largely dependent on the availability as well as local expertise. More recently, motorised spiral enteroscopy has been introduced. The main advantage of this novel DAE is ease of use with the possibility of evaluating the entire small bowel via per-oral route. However, the data regarding the use of motorised spiral enteroscopy is limited and comparative trials are required in future

Treatment of post-cholecystectomy biliary strictures with fully-covered self-expanding metal stents - results after 5 years of follow-up

BACKGROUND: Endoscopic treatment of post-cholecystectomy biliary strictures (PCBS) with multiple plastic biliary stents placed sequentially is a minimally invasive alternative to surgery but requires multiple interventions. Temporary placement of a single fully-covered self-expanding metal stent (FCSEMS) may offer safe and effective treatment with fewer re-interventions. Long-term effectiveness of treatment with FCSEMS to obtain PCBS resolution has not yet been studied. METHODS: In this prospective multi-national study in patients with symptomatic benign biliary strictures (N = 187) due to various etiologies received a FCSEMS with scheduled removal at 6-12 months and were followed for 5 years. We report here long-term outcomes of the subgroup of patients with PCBS (N = 18). Kaplan Meier analyses assessed long-term freedom from re-stenting. Adverse events were documented. RESULTS: Endoscopic removal of the FCSEMS was achieved in 83.3% (15/18) of patients after median indwell of 10.9 (range 0.9-13.8) months. In the remaining 3 patients (16.7%), the FCSEMS spontaneously migrated and passed without complications. At the end of FCSEMS indwell, 72% (13/18) of patients had stricture resolution. At 5 years after FCSEMS removal, 84.6% (95% CI 65.0-100.0%) of patients who had stricture resolution at FCSEMS removal remained stent-free. In addition, at 75 months after FCSEMS placement, the probability of remaining stent-free was 61.1% (95% CI 38.6-83.6%) for all patients. Stent or removal related serious adverse events occurred in 38.9% (7/18) all resolved without sequalae. CONCLUSIONS: In patients with symptomatic PCBS, temporary placement of a single FCSEMS intended for 10-12 months indwell is associated with long-term stricture resolution up to 5 years. Temporary placement of a single FCSEMS may be considered for patients with PCBS not involving the main hepatic confluence. TRIAL REGISTRATION NUMBERS: NCT01014390; CTRI/2012/12/003166; Registered 17 November 2009

TCF7L2 gene polymorphisms do not predict susceptibility to diabetes in tropical calcific pancreatitis but may interact with SPINK1 and CTSB mutations in predicting diabetes

<p>Abstract</p> <p>Background</p> <p>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 <it>TCF7L2 </it>gene using a case-control approach, under the hypothesis that <it>TCF7L2 </it>variants should show similar association if diabetes in FCPD is similar to T2D. We also investigated the interaction between the <it>TCF7L2 </it>variants and N34S <it>SPINK1 </it>and L26V <it>CTSB </it>mutations, since they are strong predictors of risk for TCP.</p> <p>Methods</p> <p>Two polymorphisms rs7903146 and rs12255372 in the <it>TCF7L2 </it>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 <it>SPINK1 </it>and L26V <it>CTSB </it>mutations and further subdivided them into TCP and FCPD patients and compared the distribution of <it>TCF7L2 </it>variants between them.</p> <p>Results</p> <p>The allelic and genotypic frequencies for both <it>TCF7L2 </it>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 <it>SPINK1 </it>and L26V <it>CTSB </it>mutations. The minor allele frequency for rs7903146 was different between TCP and FCPD patients carrying the N34S <it>SPINK1 </it>variant but did not reach statistical significance (OR = 1.59, 95% CI = 0.93–2.70, P = 0.09), while, <it>TCF7L2</it><it/>variant 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).</p> <p>Conclusion</p> <p>Type 2 diabetes associated <it>TCF7L2 </it>variants are not associated with diabetes in TCP. Since, <it>TCF7L2 </it>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 <it>TCF7L2 </it>variants and the <it>SPINK1 </it>and <it>CTSB </it>mutations, that predict susceptibility to exocrine damage, may interact to determine the onset of diabetes in TCP patients.</p

A novel mutation in STK11 gene is associated with Peutz-Jeghers Syndrome in Indian patients

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 286(th )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