Assessment of Capsule Endoscopy Utilizing Capsocam Plus in Patients With Suspected Small Bowel Disease Including Pilot Study With Remote Access Patients During Pandemic.

BACKGROUND: CapsoCam Plus is a capsule endoscopy (CE) system that utilizes four cameras to capture a panoramic view. This has theoretical advantage over conventional forward-viewing CE with limited field of view. Its ease of administration without requiring any additional equipment during the recording also provides a unique opportunity for patients to self-administer the test. We aimed to evaluate real-life experience using this novel system and to determine feasibility of a remote access program. METHODS: Retrospective chart review was conducted for consecutive adult outpatients who underwent CE using CapsoCam Plus. Patients with significant challenges for in-person procedures were selected for remote access through mail courier services. Gastric transit time, small bowel transit time, completion rate, diagnostic yield and adverse events were compared between remote access versus usual practice. RESULTS: Ninety-four patients (52.1% male) were included, with 28 in remote access program. Most common indication was gastrointestinal bleeding (85.1%). Complete examination was achieved in 87 patients. Five (5.3%) patients' capsule remained in stomach during the recording, while two (2.1%) patients missed capsule retrieval. Median small bowel and gastric transit times were 231.9 (interquartile range [IQR] 169.5-308.2) and 27.6 (IQR 13.8-63.5) minutes, respectively. Diagnostic yield was 23.4%. There was no difference in completion rate or transit times between two groups, but diagnostic yield was higher in remote access group (odds ratio 3.80, 95% confidence interval 1.28-11.31). One patient required elective endoscopic retrieval of capsule. CONCLUSION: CapsoCam Plus can be safely administered remotely with a high degree of success, which may facilitate timely investigations while limiting nonessential physical interactions during pandemic.

Post-traumatic Stress Disorder in Resident Physicians.

Background Research suggests that symptoms of post-traumatic stress disorder (PTSD) may be common in physicians who have experienced a traumatic event, but it is unclear if medical residents suffer from similar symptoms. Objective To determine the prevalence of PTSD symptoms in the resident physician population of the University of British Columbia based on the new Diagnostic and Statistical Manual of Mental Disorders-fifth edition (DSM-5) criteria. Method A link to an online questionnaire containing 27 questions, including residency training and year, as well as the PTSD Checklist for Diagnostic and Statistical Manual of Mental Disorders-fifth edition (PCL-5) was e-mailed and completed by the resident physicians of the University of British Columbia. Results Forty-three residents completed the survey and 38 had complete data. Mean PCL-5 score was 10.3 for the 38 subjects. Differences between PCL-5 score and resident year yielded the following: postgraduate year (PGY)-1=8.6; PGY-2=16.5; PGY-3=3.6; PGY-4=4.0; PGY-5=7.7. With respect to the type of traumatic event and PCL-5 score, the following was observed: Death=5.3, Violence=13.8, Medical Error=8.0, Bullying=38.0, None=45.0. The Kruskal-Wallis test showed no statistically significant differences in total PCL-5 score for PGY or type of traumatic event. Regardless of post-graduate year or trauma experience, four subjects out of 38 (10.5%) had a total PCL-5 score of 33 or greater, while one subject (2.5%) had a score greater than 50. Conclusion The results from this study conclude that resident physicians do suffer from PTSD symptoms at a rate higher than the average American population. As PTSD symptoms can often be very distressing and potentially affect work ethic negatively, further studies are indicated to better understand these symptoms and hopefully lead to better care in treating PTSD symptoms in resident physicians.

Capsule Endoscopy and Small Bowel Enteroscopy: Have They Rendered the Radiologist Obsolete?

Capsule endoscopy (CE) provides visualization of small bowel mucosa for evidence of inflammation. Given its ability to detect subtle mucosal changes, CE is recommended in the diagnostic work-up of small bowel Crohn disease (CD) and also in monitoring mucosal response to therapy in nonstricturing CD. Patency capsule and cross-sectional imaging can reduce risk of capsule retention in patients with suspected stenotic disease. CE is complementary to magnetic resonance enterography, which can provide extraintestinal information. Device-assisted enteroscopy has limited role in CD.

Sham Feeding with Bacon Does Not Alter Transit Time or Complete Examination Rate During Small Bowel Capsule Endoscopy.

BACKGROUND: During capsule endoscopy (CE) studies, the complete examination rate (CER) can be increased by prolonging capsule battery life or reducing gastric transit time (GTT) and/or small bowel transit time (SBTT). However, despite enhanced battery life, 10% of studies remain incomplete. Previously studied interventions to reduce SBTT and enhance CER have produced conflicting results. We hypothesize that this may be a consequence of an insufficiently potent stimulus of small bowel motility. AIMS: To examine whether potent stimulation of the cephalic response of digestion during small bowel CE reduces GTT and/or SBTT and thus increases the CER. METHODS: A single-blind randomized trial was performed to evaluate the effect of bacon sham feeding on GTT, SBTT and CER. RESULTS: Baseline characteristics were similar between 63 sham fed patients and 59 controls. The median GTT was 17 min (9-65) in the bacon group and 25 min (14-55) in the control group. The median SBTT was 199 min (119-316) and 222 min (151-287), respectively. Cox proportional hazards model demonstrated no significant difference between groups for GTT (rate ratio 1.03, 95% CI 0.71-1.51, P = 0.87) or SBTT (rate ratio 1.02, 95% CI 0.70-1.49, P = 0.93). Although the taste of bacon was considered favorably by 72% of participants, taste did not correlate with GTT (ρ = 0.03, P = 0.83) or SBTT (ρ = - 0.115, P = 0.33). The CER was 91 and 95% in the bacon and control groups, respectively (P = 0.35). CONCLUSION: Bacon sham feeding has no effect on GTT, SBTT or CER and cannot be recommended in clinical practice.

Rate of Corticosteroid-Induced Mood Changes in Patients with Inflammatory Bowel Disease: A Prospective Study.

BACKGROUND: Corticosteroid is an effective therapeutic option for inflammatory bowel disease flares, but its adverse effects may compromise treatment adherence and reduce patients' quality of life. There is lack of data on the incidence of corticosteroid-induced mood changes in this patient population, which may be underappreciated by healthcare providers in clinical practice and interfere with optimal care. This study aimed to determine the rate of mood changes in this patient population. METHODS: In this prospective observational study, adult outpatients treated with prednisone for inflammatory bowel disease flares were considered for inclusion. Participants completed validated questionnaires (Beck Depression Inventory-II and Activation Subscale of Internal State Scale version two) before starting prednisone, after two weeks of prednisone, and at the end of prednisone taper to assess for mood changes. Harvey-Bradshaw Index and Simple Clinical Colitis Activity Index were used to monitor clinical disease activity. RESULTS: Fifty-three subjects were included in the analyses. The rate of mood change after two weeks of prednisone was 49.1%, primarily driven by increase in mood towards (hypo)mania. Younger age was an independent risk factor. Mood state returned to pretreatment level at the end of treatment. There was no correlation between clinical disease activity change and mood change. CONCLUSIONS: Oral prednisone for inflammatory bowel disease flare is associated with high rate of mood change. As prednisone is a critical part of induction therapy, ways to minimize this adverse event must be studied. For now, healthcare providers should inform patients and monitor closely for this adverse event.

WMJ-8-B, a novel hydroxamate derivative, induces MDA-MB-231 breast cancer cell death via the SHP-1-STAT3-survivin cascade.

BACKGROUND AND PURPOSE: Histone deacetylase (HDAC) inhibitors have been demonstrate to have broad-spectrum anti-tumour properties and have attracted lots of attention in the field of drug discovery. However, the underlying anti-tumour mechanisms of HDAC inhibitors remain incompletely understood. In this study, we aimed to characterize the underlying mechanisms through which the novel hydroxamate-based HDAC inhibitor, WMJ-8-B, induces the death of MDA-MB-231 breast cancer cells. EXPERIMENTAL APPROACH: Effects of WMJ-8-B on cell viability, cell cycle distribution, apoptosis and signalling molecules were analysed by the MTT assay, flowcytometric analysis, immunoblotting, reporter assay, chromatin immunoprecipitation analysis and use of siRNAs. A xenograft model was used to determine anti-tumour effects of WMJ-8-B in vivo. KEY RESULTS: WMJ-8-B induced survivin reduction, G2/M cell cycle arrest and apoptosis in MDA-MB-231 cells. STAT3 phosphorylation, transactivity and its binding to the survivin promoter region were reduced in WMJ-8-B-treated cells. WMJ-8-B activated the protein phosphatase SHP-1 and when SHP-1 signalling was blocked, the effects of WMJ-8-B on STAT3 phosphorylation and survivin levels were abolished. However, WMJ-8-B increased the transcription factor Sp1 binding to the p21 promoter region and enhanced p21 levels. Moreover, WMJ-8-B induced α-tubulin acetylation and disrupted microtubule assembly. Inhibition of HDACs was shown to contribute to WMJ-8-B's actions. Furthermore, WMJ-8-B suppressed the growth of MDA-MB-231 xenografts in mammary fat pads in vivo. CONCLUSIONS AND IMPLICATIONS: The SHP-1-STAT3-survivin and Sp1-p21 cascades are involved in WMJ-8-B-induced MDA-MB-231 breast cancer cell death. These results also indicate the potential of WMJ-8-B as a lead compound for treatment of breast cancer and warrant its clinical development.

Utility of Transient Elastography in Estimating Hepatic Iron Concentration in Comparison to Magnetic Resonance Imaging in Patients Who are Transfusion-Dependent: A Canadian Center Experience.

Transfusion-dependent hereditary anemias such as ß-thalassemia (ß-thal), predispose patients to iron overload and its numerous clinical sequelae. Accurate assessment of overall iron status and prompt initiation of chelation therapy to prevent irreversible end-organ damage can be achieved using magnetic resonance imaging (MRI) to measure liver iron concentration (LIC) as a surrogate marker of total body iron; however, its access may be associated with long wait times and delay in treatment. We report an observational cohort study at a single tertiary care center assessing the theoretical role of transient elastography (TE), which measures liver stiffness, in estimating LIC compared to other established diagnostic measures. While regression analyses confirm a moderate correlation between LIC per R2 MRI and serum ferritin level (pooled estimate of correlation = 0.55), there was no significant correlation between TE reading and LIC based on R2 MRI (pooled estimate of correlation = -0.06), and only a weak correlation was observed with serum ferritin level (pooled estimate of correlation = 0.45). These results suggest TE may not be sensitive enough to detect subtle changes in the hepatic parenchymal stiffness associated with liver iron deposition.

When trainees reach competency in performing endoscopic ultrasound: a systematic review.

Background/Study aim The American Society for Gastrointestinal Endoscopy (ASGE) recommends that trainees complete 150 endoscopic ultrasound (EUS) procedures before assessing competency. However, this recommendation is largely based on limited evidence and expert opinion. With new evidence suggesting that this historical threshold is underestimating training requirements, we evaluated the learning curve for achieving competency in EUS. Patients/Materials and methods Two investigators independently searched MEDLINE for full-text citations assessing the learning curve for achieving competency in EUS in the period 1946 to 25 March 2016. A learning curve was defined as either a tabulated or graphic representation of competency as a function of increasing EUS experience. Results Eight studies assessing 28 trainees and 7051 EUS procedures were included. When stratifying studies based on procedural indication: three studies assessed competency in evaluating mucosal lesions, three studies assessed competency in EUS fine-needle aspiration (EUS-FNA), and two studies assessed comprehensive competency. Among studies assessing mucosal lesion T-staging accuracy, competency was achieved by 65 to 231 procedures. Among studies assessing EUS-FNA, competency was achieved by 30 to 40 procedures. Among the two studies assessing comprehensive competency in EUS, competency was not achieved in either study across all trainees. Only four of 17 trainees reached competency by 225 to 295 EUS procedures. Conclusion As EUS competency assessment has evolved to more closely reflect independent clinical practice, the number of procedures required to achieve competency has risen well above ASGE recommendations. Advanced endoscopy training programs and specialty societies need to re-assess the structure of EUS training.

Interleukin-6 Induces Vascular Endothelial Growth Factor-C Expression via Src-FAK-STAT3 Signaling in Lymphatic Endothelial Cells.

Elevated serum interleukin-6 (IL-6) levels correlates with tumor grade and poor prognosis in cancer patients. IL-6 has been shown to promote tumor lymphangiogenesis through vascular endothelial growth factor-C (VEGF-C) induction in tumor cells. We recently showed that IL-6 also induced VEGF-C expression in lymphatic endothelial cells (LECs). However, the signaling mechanisms involved in IL-6-induces VEGF-C induction in LECs remain incompletely understood. In this study, we explored the causal role of focal adhesion kinase (FAK) in inducing VEGF-C expression in IL-6-stimulated murine LECs (SV-LECs). FAK signaling blockade by NSC 667249 (a FAK inhibitor) attenuated IL-6-induced VEGF-C expression and VEGF-C promoter-luciferase activities. IL-6's enhancing effects of increasing FAK, ERK1/2, p38MAPK, C/EBPß, p65 and STAT3 phosphorylation as well as C/EBPß-, κB- and STAT3-luciferase activities were reduced in the presence of NSC 667249. STAT3 knockdown by STAT3 siRNA abrogated IL-6's actions in elevating VEGF-C mRNA and protein levels. Moreover, Src-FAK signaling blockade reduced IL-6's enhancing effects of increasing STAT3 binding to the VEGF-C promoter region, cell migration and endothelial tube formation of SV-LECs. Together these results suggest that IL-6 increases VEGF-C induction and lymphangiogenesis may involve, at least in part, Src-FAK-STAT3 cascade in LECs.

Lovastatin causes FaDu hypopharyngeal carcinoma cell death via AMPK-p63-survivin signaling cascade.

Statins are used widely to lower serum cholesterol and the incidence of cardiovascular diseases. Growing evidence shows that statins also exhibit beneficial effects against cancers. In this study, we investigated the molecular mechanisms involved in lovastatin-induced cell death in Fadu hypopharyngeal carcinoma cells. Lovastatin caused cell cycle arrest and apoptosis in FaDu cells. Lovastatin increased p21(cip/Waf1) level while the survivin level was decreased in the presence of lovastatin. Survivin siRNA reduced cell viability and induced cell apoptosis in FaDu cells. Lovastatin induced phosphorylation of AMP-activated protein kinase (AMPK), p38 mitogen-activated protein kinase (MAPK) and transcription factor p63. Lovastatin also caused p63 acetylation and increased p63 binding to survivin promoter region in FaDu cells. AMPK-p38MAPK signaling blockade abrogated lovastatin-induced p63 phosphorylation. Lovastatin's enhancing effect on p63 acetylation was reduced in HDAC3- or HDAC4- transfected cells. Moreover, transfection of cells with AMPK dominant negative mutant (AMPK-DN), HDAC3, HDAC4 or p63 siRNA significantly reduced lovastatin's effects on p21(cip/Waf1) and survivin. Furthermore, lovastatin inhibited subcutaneous FaDu xenografts growth in vivo. Taken together, lovastatin may activate AMPK-p38MAPK-p63-survivin cascade to cause FaDu cell death. This study establishes, at least in part, the signaling cascade by which lovastatin induces hypopharyngeal carcinoma cell death.

Bevacizumab and gastrointestinal bleeding in hereditary hemorrhagic telangiectasia.

We report a case of severe, refractory gastrointestinal (GI) bleeding in a patient with hereditary hemorrhagic telangiectasia (HHT) whose massive transfusion dependence was lifted shortly after treatment with bevacizumab, an anti-vascular endothelial growth factor. The patient's bleeding had been refractory to repeated endoscopic interventions, tranexamic acid, and tamoxifen. However, following treatment with bevacizumab at 5 mg/kg every other week, nearly 300 units of packed red blood cell transfusions were avoided in one year's time. Despite its relatively high cost, bevacizumab may have a more active role in the management of severe GI bleeding in HHT if such remarkable response can be consistently demonstrated.

Identification of factors associated with sedation tolerance in 5000 patients undergoing outpatient colonoscopy: Canadian tertiary center experience.

AIM: To develop a prediction model aimed at identifying patients that may require higher than usual sedation doses during colonoscopy. METHODS: A retrospective chart review on 5000 patients who underwent an outpatient colonoscopy at St. Paul's Hospital from 2009 to 2010 was conducted in order to develop a model for identifying patients who will require increased doses of sedatives. Potential predictor variables including age, gender, endoscopy indication, high sedation requirements during previous endoscopies, difficulty of the procedure, bowel preparation quality, interventions, findings as well as current use of benzodiazepines, opioids and alcohol were analyzed. The outcome of study was the use of high dose of sedation agents for the procedure. In particular, the high dose of sedation was defined as fentanyl greater than 50 mcg and midazolam greater than 3 mg. RESULTS: Analysis of 5282 patients (mean age 57 ± 12, 49% female) was performed. Most common indication for the procedure was screening colonoscopy (57%). Almost half of our patients received doses exceeding Fentanyl 50 mcg and Midazolam 3 mg. Logistic regression models identified the following variables associated with high sedation: Younger age (OR = 0.95 95%CI: 0.94-0.95; P < 0.0001); abdominal pain (OR = 1.45, 95%CI: 1.08-1.96); P = 0.01) and Inflammatory Bowel Disease (OR = 1.45, 95%CI: 1.04-2.03; P = 0.02) as indications for the procedure; difficult procedure as defined by gastroenterologist (OR = 1.73, 95%CI: 1.48-2.03; P < 0.0001); past history of abdominal surgery (OR = 1.33, 95%CI: 1.17-1.52; P <0.0001) and previous colonoscopy (OR = 1.39, 95%CI: 1.21-1.60; P = 0.0001) and alcohol use (OR = 1.26, 95%CI: 1.03-1.54; P = 0.02). Age and gender adjusted analysis yielded inflammatory bowel disease as an indication (OR = 3.17, 95%CI: 1.58-6.37; P = 0.002); difficult procedure as defined by an endoscopist (OR = 5.13 95%CI: 2.97-8.85; P = 0.0001) and current use of opioids, benzodiazepines or antidepressants (OR = 2.88, 95%CI: 1.74-4.77; P = 0.001) having the highest predictive value of high sedation requirements. Our prediction model using the following pre-procedural variables including age, gender, indication for the procedure, medication/substance use, previous surgeries, previous high sedation requirements for colonoscopy yielded an area under the curve of 0.76 for Fentanyl ≥ 100 mcg and Midazolam ≥ 3 mg. CONCLUSION: Pre-procedural planning is the key in conducting successful, efficient colonoscopy. Logistic regression analysis of 5000 patients who underwent out-patient colonoscopy revealed the following factors associated with increased sedation requirement: Younger age, female gender, difficult endoscopy, specific indications as well as cardiopulmonary complications and current use of opioids/benzodiazepines. Age and gender adjusted analysis yielded similar results. These patients are more likely to need a longer recovery periods post-endoscopy, which could result in additional time and personnel requirements. The final predictive model has good predictive ability for Fentanyl ≥ 100 mcg and Midazolam ≥ 3 mg and fair predictive ability for Fentanyl ≥ 50 mcg and Midazolam ≥ 2 mg. The external validity of this model is planned to be tested in another center.

Prevalence, Timing, Causes, and Outcomes of Hyponatremia in Hospitalized Orthopaedic Surgery Patients.

BACKGROUND: Hyponatremia is common among orthopaedic patients and is associated with adverse clinical outcomes. We examined the prevalence, timing, causes, and outcomes of hyponatremia in adult hospitalized orthopaedic surgery patients. METHODS: We evaluated the medical records of 1067 consecutive orthopaedic surgery patients admitted to a tertiary academic institution. The medical records were reviewed to investigate hyponatremia (serum sodium <135 mEq/L) that (1) had been present on hospital admission or (2) had developed postoperatively. The primary outcomes were the prevalence and timing of, and risk factors for, presentation with or development of hyponatremia. Secondary outcomes were hospital length of stay, total hospital cost, and discharge disposition. Multivariable logistic regression models were used to assess the variables associated with hyponatremia and the effects of hyponatremia on clinical outcomes. RESULTS: Of the 1067 patients, seventy-one (7%) had preoperative hyponatremia and 319 (30%) developed hyponatremia postoperatively. Of the latter, 298 (93%) developed hyponatremia within forty-eight hours postoperatively. Compared with patients with normonatremia, those who presented with hyponatremia, on the average, were older (67.2 versus 60.5 years, p < 0.001), had longer hospital stays (4.6 versus 3.3 days, p < 0.001), incurred higher hospital costs ($19,200 versus $17,000, p = 0.006), and were more likely to be discharged to an extended-care facility (odds ratio [OR] = 2.87, p < 0.001). Developing hyponatremia postoperatively resulted, on average, in a longer hospital stay (3.7 versus 3.3 days, p = 0.002) and greater hospital cost ($18,800 versus $17,000, p < 0.001). Age (OR = 1.13 per decade, p = 0.012), spine surgery (OR = 2.76 versus knee, p < 0.001), hip surgery (OR = 1.76 versus knee, p < 0.001), and the amount of lactated Ringer solution used (OR = 1.16, p = 0.002) increased the risk of developing hyponatremia. CONCLUSIONS: Hyponatremia in orthopaedic patients is associated with longer, costlier hospitalizations. The factors that significantly increased the risk of developing postoperative hyponatremia were an older age, spine fusion, hip arthroplasty, and the amount of lactated Ringer solution used.

The effects of a novel aliphatic-chain hydroxamate derivative WMJ-S-001 in HCT116 colorectal cancer cell death.

Hydroxamate derivatives have attracted considerable attention due to their broad pharmacological properties and have been extensively investigated. We recently demonstrated that WMJ-S-001, a novel aliphatic hydroxamate derivative, exhibits anti-inflammatory and anti-angiogenic activities. In this study, we explored the underlying mechanisms by which WMJ-S-001 induces HCT116 colorectal cancer cell death. WMJ-S-001 inhibited cell proliferation and induced cell apoptosis in HCT116 cells. These actions were associated with AMP-activated protein kinase (AMPK) and p38 mitogen-activated protein kinase (MAPK) activation, p53 phosphorylation and acetylation, as well as the modulation of p21(cip/Waf1), cyclin D1, survivin and Bax. AMPK-p38MAPK signaling blockade reduced WMJ-S-001-induced p53 phosphorylation. Transfection with AMPK dominant negative mutant (DN) reduced WMJ-S-001's effects on p53 and Sp1 binding to the survivn promoter region. Transfection with HDAC3-Flag or HDAC4-Flag also abrogated WMJ-S-001's enhancing effect on p53 acetylation. WMJ-S-001's actions on p21(cip/Waf1), cyclin D1, survivin, Bax were reduced in p53-null HCT116 cells. Furthermore, WMJ-S-001 was shown to suppress the growth of subcutaneous xenografts of HCT116 cells in vivo. In summary, the death of HCT116 colorectal cancer cells exposed to WMJ-S-001 may involve AMPK-p38MAPK-p53-survivin cascade. These results support the role of WMJ-S-001 as a potential drug candidate and warrant the clinical development in the treatment of cancer.

Protein Phosphatase 2A in Lipopolysaccharide-Induced Cyclooxygenase-2 Expression in Murine Lymphatic Endothelial Cells.

The lymphatic endothelium plays an important role in the maintenance of tissue fluid homeostasis. It also participates in the pathogenesis of several inflammatory diseases. However, little is known about the underlying mechanisms by which lymphatic endothelial cell responds to inflammatory stimuli. In this study, we explored the mechanisms by which lipopolysaccharide (LPS) induces cyclooxygenase (COX)-2 expression in murine lymphatic endothelial cells (SV-LECs). LPS caused increases in cox-2 mRNA and protein levels, as well as in COX-2 promoter luciferase activity in SV-LECs. These actions were associated with protein phosphatase 2A (PP2A), apoptosis signal-regulating kinase 1 (ASK1), JNK1/2 and p38MAPK activation, and NF-κB subunit p65 and C/EBPß phosphorylation. PP2A-ASK1 signaling blockade reduced LPS-induced JNK1/2, p38MAPK, p65 and C/EBPß phosphorylation. Transfection with PP2A siRNA reduced LPS's effects on p65 and C/EBPß binding to the COX-2 promoter region. Transfected with the NF-κB or C/EBPß site deletion of COX-2 reporter construct also abrogated LPS's enhancing effect on COX-2 promoter luciferase activity in SV-LECs. Taken together, the induction of COX-2 in SV-LECs exposed to LPS may involve PP2A-ASK1-JNK and/or p38MAPK-NF-κB and/or C/EBPß cascade.

Colonoscopy after CT-diagnosed acute diverticulitis: Is it really necessary?

BACKGROUND: Computed tomography (CT) scans are commonly used to diagnose acute diverticulitis, but there are overlapping features between diverticulitis and colorectal cancer (CRC) on imaging studies. Hence, colonoscopy is typically recommended after an episode of acute diverticulitis to rule out underlying malignancy. Currently, 64-slice multidetector CT scanners are capable of providing higher-resolution images and may be able to distinguish malignancy from diverticular inflammation. We aimed to determine the prevalence of CRC among patients with CT-diagnosed acute diverticulitis. METHODS: We performed a retrospective study of patients with acute diverticulitis diagnosed on CT scan between December 2005 and December 2010 at St. Paul's Hospital, Vancouver, BC. Nonresidents were excluded. We reviewed CT scan reports that included the term "diverticulitis," reports of follow-up colonic evaluation within 1 year of diagnosis and pathology results. We queried the provincial cancer registry to ensure no cases of CRC were missed. RESULTS: A total of 293 patients had acute diverticulitis diagnosed on CT scan, but 8 were nonresidents and were excluded. Of the 285 included in the analysis, the mean age was 59.4 ± 15.1 years, and 167 (58.6%) were men. Among the 114 patients who underwent follow-up evaluation, malignancy was diagnosed in 4 (3.5%). The overall prevalence of malignancy among patients with CT-diagnosed diverticulitis was 1.4%. CONCLUSION: Routine endoscopic evaluation after an episode of diverticulitis diagnosed with high-resolution CT scan does not appear to be necessary. Selective approach in patients with protracted clinical course or those with mass lesion/obstruction on CT scan may be of benefit.

CONTEXTE: La tomodensitométrie (TDM) est couramment utilisée pour le diagnostic de la diverticulite aiguë, mais des caractéristiques sont communes à la diverticulite et au cancer colorectal (CCR) aux épreuves d'imagerie. On recommande donc en général la coloscopie après un épisode de diverticulite aiguë pour écarter un diagnostic de cancer sous-jacent. À l'heure actuelle, les appareils de TDM multidétecteurs à 64 barrettes peuvent fournir des images de haute résolution et permettent même de distinguer le cancer d'une inflammation diverticulaire. Nous avons voulu déterminer la prévalence du CCR chez les patients ayant présenté une diverticulite aiguë diagnostiquée par TDM. MÉTHODES: Nous avons procédé à une étude rétrospective sur des patients porteurs d'une diverticulite aiguë diagnostiquée à l'aide de TDM entre décembre 2005 et décembre 2010 à l'Hôpital St. Paul's de Vancouver, en Colombie-Britannique. Les non-résidents ont été exclus. Nous avons examiné les rapports de TDM incluant le terme « diverticulite ¼, les rapports d'examens du côlon au cours de l'année suivant le diagnostic et les rapports d'anatomopathologie. Nous avons interrogé le registre provincial sur le cancer pour nous assurer qu'aucun cas de CCR ne nous avait échappé. RÉSULTATS: En tout, 293 patients ont reçu un diagnostic de diverticulite à l'aide de la TDM; 8 étaient des non-résidents et ont été exclus. Parmi les 285 patients inclus dans l'analyse, l'âge moyen était de 59,4 ± 15,1 ans et 167 (58,6 %) étaient des hommes. Parmi les 114 patients qui ont subi un examen de suivi, le cancer a été diagnostiqué chez 4 (3,5 %). La prévalence globale du cancer chez les patients porteurs d'un diagnostic de diverticulite posé par TDM était de 1,4 %. CONCLUSION: L'évaluation endoscopique de routine après un épisode de diverticulite diagnostiquée à l'aide d'une TDM de haute résolution ne semble pas nécessaire. Une approche sélective chez les patients qui présentent une évolution clinique lente ou ceux qui présentent une lésion ou obstruction tumorale à la TDM pourrait être utile.

When trainees reach competency in performing ERCP: a systematic review.

BACKGROUND AND AIMS: ERCP is an advanced endoscopic procedure that is technically more challenging and carries a higher risk of adverse events compared with standard endoscopy. A discrepancy currently exists among guidelines regarding the number of ERCPs that a trainee needs to complete before procedural competency should be assessed. Our aim was to assess the learning curve for performing ERCP. METHODS: Two authors independently searched MEDLINE (1946 to November 25, 2014) along with the gray literature to identify relevant citations. To warrant inclusion, citations were required to report successful trainee cannulation rate. Successful cannulation rate, set at a value of 80% or higher, was used as our baseline reference for competency. RESULTS: Nine studies, assessing 137 trainees and 17,100 ERCPs, were included in our analysis. Overall, competency was achieved among the included studies between 70 to 400 ERCPs. In the 2 studies that used pancreatic duct cannulation rate, competency was achieved by 70 to 160 ERCPs. Of the 5 studies that used selective duct cannulation rate, competency was achieved by 79 to 300 ERCPs. Finally, in the 4 studies that used common bile duct cannulation rate, 2 studies reached the reference competency threshold by 160 to 400 ERCPs. On further stratification, when assessing native papilla deep common bile duct cannulation, only 1 study reached the reference competency threshold by 350 to 400 ERCPs. CONCLUSIONS: Our findings suggest that as ERCP has evolved from a predominantly diagnostic to therapeutic procedure, procedural thresholds have risen well above North American training guidelines. Therefore, advanced endoscopy training programs need to reassess their current structure to ensure that procedural competency is being reached.

Effect of longer battery life on small bowel capsule endoscopy.

AIM: To determine if longer battery life improves capsule endoscopy (CE) completion rates. METHODS: A retrospective study was performed at a tertiary, university-affiliated hospital in Vancouver, Canada. Patients who underwent CE with either PillCam™ SB2 or SB2U between 01/2010 and 12/2013 were considered for inclusion. SB2 and SB2U share identical physical dimensions but differ in their battery lives (8 h vs 12 h). Exclusion criteria included history of gastric or small bowel surgery, endoscopic placement of CE, interrupted view of major landmarks due to technical difficulty or significant amount of debris, and repeat CE using same system. Basic demographics, comorbidities, medications, baseline bowel habits, and previous surgeries were reviewed. Timing of major landmarks in CE were recorded, and used to calculate gastric transit time, small bowel transit time, and total recording time. A complete CE study was defined as visualization of cecum. Transit times and completion rates were compared. RESULTS: Four hundred and eight patients, including 208 (51.0%) males, were included for analysis. The mean age was 55.5 ± 19.3 years. The most common indication for CE was gastrointestinal bleeding (n = 254, 62.3%), followed by inflammatory bowel disease (n = 86, 21.1%). There was no difference in gastric transit times (group difference 0.90, 95%CI: 0.72-1.13, P = 0.352) and small bowel transit times (group difference 1.07, 95%CI: 0.95-1.19, P = 0.261) between SB2U and SB2, but total recording time was about 14% longer in the SB2U group (95%CI: 10%-18%, P < 0.001) and there was a corresponding trend toward higher completion rate (88.2% vs 93.2%, OR = 1.78, 95%CI 0.88-3.63, P = 0.111). There was no statistically significant difference in the rates of positive findings (OR = 0.98, 95%CI: 0.64-1.51, P = 0.918). CONCLUSION: Extending the operating time of CE may be a simple method to improve completion rate although it does not affect the rate of positive findings.

WMJ-S-001, a novel aliphatic hydroxamate derivative, exhibits anti-angiogenic activities via Src-homology-2-domain-containing protein tyrosine phosphatase 1.

Angiogenesis, one of the major routes for tumor invasion and metastasis represents a rational target for therapeutic intervention. Recent development in drug discovery has highlighted the diverse biological and pharmacological properties of hydroxamate derivatives. In this study, we characterized the anti-angiogenic activities of a novel aliphatic hydroxamate, WMJ-S-001, in an effort to develop novel angiogenesis inhibitors. WMJ-S-001 inhibited vascular endothelial growth factor (VEGF)-A-induced proliferation, invasion and endothelial tube formation of human umbilical endothelial cells (HUVECs). WMJ-S-001 suppressed VEGF-A-induced microvessel sprouting from aortic rings, and attenuated angiogenesis in in vivo mouse xenograft models. In addition, WMJ-S-001 inhibited the phosphorylations of VEGFR2, Src, FAK, Akt and ERK in VEGF-A-stimulated HUVECs. WMJ-S-001 caused an increase in SHP-1 phosphatase activity, whereas NSC-87877, a SHP-1 inhibitor, restored WMJ-S-001 suppression of VEGFR2 phosphorylation and cell proliferation. Furthermore, WMJ-S-001 inhibited cell cycle progression and induced cell apoptosis in HUVECs. These results are associated with p53 phosphorylation and acetylation and the modulation of p21 and survivin. Taken together, WMJ-S-001 was shown to modulate vascular endothelial cell remodeling through inhibiting VEGFR2 signaling and induction of apoptosis. These results also support the role of WMJ-S-001 as a potential drug candidate and warrant the clinical development in the treatment of cancer.