Calvin Chan

InnateDB: facilitating systems‐level analyses of the mammalian innate immune response

Although considerable progress has been made in dissecting the signaling pathways involved in the innate immune response, it is now apparent that this response can no longer be productively thought of in terms of simple linear pathways. InnateDB (www.innatedb.ca) has been developed to facilitate systems‐level analyses that will provide better insight into the complex networks of pathways and interactions that govern the innate immune response. InnateDB is a publicly available, manually curated, integrative biology database of the human and mouse molecules, experimentally verified interactions and pathways involved in innate immunity, along with centralized annotation on the broader human and mouse interactomes. To date, more than 3500 innate immunity‐relevant interactions have been contextually annotated through the review of 1000 plus publications. Integrated into InnateDB are novel bioinformatics resources, including network visualization software, pathway analysis, orthologous interaction network construction and the ability to overlay user‐supplied gene expression data in an intuitively displayed molecular interaction network and pathway context, which will enable biologists without a computational background to explore their data in a more systems‐oriented manner.

Curating the innate immunity interactome.

BackgroundThe innate immune response is the first line of defence against invading pathogens and is regulated by complex signalling and transcriptional networks. Systems biology approaches promise to shed new light on the regulation of innate immunity through the analysis and modelling of these networks. A key initial step in this process is the contextual cataloguing of the components of this system and the molecular interactions that comprise these networks. InnateDB (http://www.innatedb.com) is a molecular interaction and pathway database developed to facilitate systems-level analyses of innate immunity.ResultsHere, we describe the InnateDB curation project, which is manually annotating the human and mouse innate immunity interactome in rich contextual detail, and present our novel curation software system, which has been developed to ensure interactions are curated in a highly accurate and data-standards compliant manner. To date, over 13,000 interactions (protein, DNA and RNA) have been curated from the biomedical literature. Here, we present data, illustrating how InnateDB curation of the innate immunity interactome has greatly enhanced network and pathway annotation available for systems-level analysis and discuss the challenges that face such curation efforts. Significantly, we provide several lines of evidence that analysis of the innate immunity interactome has the potential to identify novel signalling, transcriptional and post-transcriptional regulators of innate immunity. Additionally, these analyses also provide insight into the cross-talk between innate immunity pathways and other biological processes, such as adaptive immunity, cancer and diabetes, and intriguingly, suggests links to other pathways, which as yet, have not been implicated in the innate immune response.ConclusionsIn summary, curation of the InnateDB interactome provides a wealth of information to enable systems-level analysis of innate immunity.

Endoscopic Management of Benign Biliary Strictures

Endoscopic retrograde cholangiopancreatography (ERCP) is the first-line management in most situations when a benign biliary stricture is suspected. Although management principles are similar in all subgroups, the anticipated response rates, need for ancillary medical and endoscopic approaches, and use of less proven strategies vary between differing causes. Exclusion of malignancy should always be a focus of management. Newer endoscopic techniques such as endoscopic ultrasound, cholangioscopy, confocal endomicroscopy, and metal biliary stenting are increasingly complementing traditional ERCP techniques in achieving long-term sustained stricture resolution. Surgery remains a definitive management alternative when a prolonged trial of endoscopic therapy does not achieve treatment goals.

The effect of chewing gum on small-bowel transit time in capsule endoscopy: a prospective, randomized trial.

BACKGROUND Approximately 1 in 6 capsule endoscopies (CEs) does not visualize the entire small bowel at completion of the examination because of limited battery life. OBJECTIVE To determine whether chewing gum can reduce the small-bowel transit time and increase CE completion rates. DESIGN Prospective, single-blind, randomized, controlled trial. SETTING A tertiary university-affiliated hospital. PATIENTS Consecutive patients 19 years of age and older undergoing outpatient small-bowel CE from October 2010 to July 2012 were assessed for eligibility. Those with previous gastric or small-bowel surgery or ileostomy, dysphagia prohibiting capsule ingestion, diabetes mellitus with evidence of end-organ damage, use of narcotics or prokinetics within 5 days before the procedure, clinical hyper-/hypothyroidism, and symptoms suggestive of acute bowel obstruction were excluded. INTERVENTION Gum chewing for at least 20 minutes every 2 hours starting at the time of capsule ingestion. MAIN OUTCOME MEASUREMENTS Small-bowel transit time, gastric transit time, and completion rate were measured. RESULTS Chewing gum did not have any significant effect on gastric transit time (rate ratio 1.06; 95% CI, 0.73-1.55; P = .75), small-bowel transit time (rate ratio 0.91; 95% CI, 0.62-1.35; P = .65), or completion rate (91.67% chewing gum vs 88.71% control, P = .58) of CE. LIMITATION Single-center study involving relatively healthy subjects. Procedures were done on an outpatient basis so participants were not monitored for adherence to protocol. CONCLUSIONS Chewing gum does not speed up capsule transit or increase completion rate of CE in patients without risk factors for incomplete studies. ( CLINICAL TRIAL REGISTRATION NUMBER NCT01241825.).

Response to endoscopic therapy for biliary anastomotic strictures in deceased versus living donor liver transplantation

BACKGROUND Endoscopic therapy has been successful in the management of biliary complications after both deceased donor liver transplantation (DDLT) and living donor liver transplantation (LDLT). LDLT is thought to be associated with higher rates of biliary complications, but there are few studies comparing the success of endoscopic management of anastomotic strictures between the two groups. This study aims to compare our experience in the endoscopic management of anastomotic strictures in DDLT versus LDLT. METHODS This is a retrospective database review of all liver transplant patients undergoing endoscopic retrograde cholangiopancreatography (ERCP) after liver transplantation. The frequency of anastomotic stricture and the time to develop and to resolve anastomotic stricture were compared between DDLT and LDLT. The response of anastomotic stricture to endoscopic therapy was also analyzed. RESULTS A total of 362 patients underwent liver transplantation between 2003 and 2011, with 125 requiring ERCP to manage biliary complications. Thirty-three (9.9%) cases of DDLT and 8 (27.6%) of LDLT (P=0.01) were found to have anastomotic stricture. When comparing DDLT and LDLT, there was no difference in the mean time to the development of anastomotic strictures (98+/-17 vs 172+/-65 days, P=0.11), likelihood of response to ERCP [22 (66.7%) vs 6 (75.0%), P=0.69], mean time to the resolution of anastomotic strictures (268+/-77 vs 125+/-37 days, P=0.34), and the number of ERCPs required to achieve resolution (3.9+/-0.4 vs 4.7+/-0.9, P=0.38). CONCLUSIONS Endoscopic therapy is effective in the majority of biliary complications relating to liver transplantation. Anastomotic strictures occur more frequently in LDLT compared with DDLT, with equivalent endoscopic treatment response and outcomes for both groups.

A Novel Two-Step Approach for Retrieval of an Impacted Biliary Extraction Basket

Biliary extraction baskets are a commonly used instrument for the removal of choledocholithiasis in endoscopic retrograde cholangiopancreatography (ERCP). Impaction of the extraction basket is a recognized complication of ERCP, and is usually the result of discrepancy between the size of bile duct stone and the diameter of the distal bile duct. Whilst mechanical lithotriptors can be used to crush the stone or break the wires of the basket to allow its release, failure of the lithotriptor device can occur. We describe the case of a 59-year-old gentleman who had an ERCP performed for choledocholithiasis. Basket impaction was encountered, and the mechanical lithotriptor failed to dislodge the stone/basket complex. A two-step technique involving balloon dilatation and forceps manipulation of the basket was applied to successfully dislodge the impacted basket. We believe this simple and safe technique should be adopted to rescue impacted biliary extraction baskets to avoid the need for potential surgical removal.

Esophageal squamous papilloma lacks clear clinicopathological associations

AIM To determine the prevalence of esophageal squamous papillomas (ESPs) in a tertiary teaching hospital and to assess for any clinical associations, including relations with esophageal squamous cell carcinomas (SCCs). METHODS Data from a total of 6962 upper gastrointestinal endoscopies over a five year period were retrospectively obtained and analysed. RESULTS ESP was found in sixteen patients (0.23%). Eight (50%) patients had a high body mass index, seven (44%) had history of cigarette smoking. Reflux esophagitis was found in four (25%) patients. All ESPs were solitary with a mean endoscopic size of 3.8 mm and located in the mid to lower esophagus. Human papilloma virus (HPV) was tested in three (19%) patients and was negative. Esophageal SCC was found in seven patients (0.10%) during the same period. None of the specimens were tested for HPV, and none had associated papillomatous changes. CONCLUSION ESP is an uncommon tumour with unclear clinical associations and malignant potential.

An Uncommon Complication of Percutaneous Endoscopic Gastrostomy Tube Placement

Question: A 75-year-old nursing home resident was referred by her local medical officer with a 5-month history of an enlarging exophytic growth from around her percutaneous endoscopic gastrostomy (PEG) site. Her initial PEG was placed 7 years prior, when she suffered a large cerebral hemorrhage, with secondary oropharyngeal dysphagia. At the time, she was already suffering from early cognitive impairment, which had progressed over the subsequent years. The growth was noticed after a new feeding tube was replaced percutaneously, without endoscopic assistance, when the previous PEG was accidentally dislodged. In the months leading up to her assessment, there were observations from the patient’s family of altered behavior, including frequent gesturing at the PEG site, suggestive of some associated discomfort. Examination of the PEG site revealed a 3-cm, exophytic, fleshy mass that encircled the PEG tube (Figure A). No ulceration was evident. The origin of the lesion seemed to arise deep to the cutaneous layer. The PEG tube seemed to be freely mobile and was in good position. No evidence of organomegaly, ascites, or peritonism was identified on examination. A biopsy was performed of the lesion (Figure B). Computed tomography was performed (Figure C–E). What is the diagnosis? See the Gastroenterology web site (www.gastrojournal.org) for more information on submitting your favorite image to Clinical Challenges and Images in GI.

Repeat Procedures Within 30 days in Patients Stented for Malignant Distal Biliary Strictures: Experience of 508 Patients at a Tertiary Referral Center

Background Stent related occlusion and migration remains a problem despite attempts to improve stent design over this time period. Flanged polyethylene plastic stents (FPS) remains the stent of choice in most centers. Early failure of stents placed for malignant extrahepatic biliary strictures (MEBS) has not previously been studied in detail. We set out to determine the incidence and reasons for biliary stent change within 30 days of the index procedure in a large tertiary center population during a period where (FPS) was the sole plastic stent used. Methods Retrospective analysis of endoscopic retrograde cholangiography (ERCP) was undertaken in patients who were stented for presumed or known MEBS between 1993 and 2001. Patients who required repeat stenting within 30 days were identified. Results All 508 patients were stented for MEBS. 5.7% of patients had a total of 34 repeat stenting procedures within 30 days of the index procedure; 27of 29 index stents were plastic, 2 were self-expandable metal stents (SEMS), 20 (3.9%) patients had stent failure as the reason for a stent exchange (plastic stent occlusion n = 15, mean time to stent change 14 ± 8.3 days; metal stent occlusion n = 2, mean time to stent change 24.5 ± 7.8 days; plastic stent migration n = 3, mean time to stent change 25 ± 5.3 days). There was a statistically significant difference in the time to stent change between the occluded plastic stent and migrated plastic stent cases (P = 0.045, 95% CI -21.7 to -0.29). 6 patients spent at least 2 additional days in hospital as a result of stent failure. Conclusions Early stent failure is an uncommon problem, especially in patients with SEMS. Early plastic stent failure appears to occur sooner with stent occlusion than with stent migration. Early stent failure is associated with significant morbidity and bears an economic impact in additional procedures and hospital stay.