CYP2C19 phenotype in South-East Asian Acute Coronary Syndrome patients and impact on major adverse cardiovascular events.

WHAT IS KNOWN AND OBJECTIVE: Several Caucasian cohort studies have associated at least one loss-of-function CYP2C19 on Clopidogrel (LoF-Clopidogrel) with major adverse cardiovascular events (MACE), and only a couple have used Clinical Pharmacogenetics Implementation Consortium (CPIC® ) phenotype grouping to study the associations. We primarily aimed to study the impact of use of platelet reactivity testing to escalate antiplatelet therapy and secondarily to study the association of CPIC phenotype with MACE outcomes in South-East Asian Acute Coronary Syndrome (ACS) subjects. METHOD: A retrospective genotype study was performed on 238 percutaneous coronary intervention subjects, originally planned for escalation of antiplatelets using platelet reactivity testing. RESULTS AND DISCUSSION: There was no difference in MACE between the switched and unswitched groups; however, 'all bleeds' and 'clinically significant bleeds' (CSB) were statistically higher in the patients who were switched to prasugrel. The subgroup of patients who remained on clopidogrel (n = 199) were analysed using phenotype categories and MACE. Eleven percent (11.4%) of CYP2C19 poor metabolizers (PM) suffered MACE, compared with 1.3% of extensive metabolizers (EM). LoF-Clopidogrel patients are significantly more likely to experience MACE compared with non-LoF subjects (8.0% vs 5.4%, P: .041). WHAT IS NEW AND CONCLUSION: In our multivariate analysis, LoF-Clopidogrel, malay ethnicity, diabetics and use of proton pump inhibitors were independent predictors of MACE. There were numerically more bleeds in LoF subjects who were on prasugrel compared with Clopidogrel (23.5% vs 11%, P = .082). Our data corroborate with current findings on platelet reactivity testing, suggesting that the assay would not be sensitive enough to pick up sufficient 'at-risk' subjects as compared to the use of CYP2C19 genotyping.

Risk of Major Abdominal Surgery in an Asian Population-based Crohn's Disease Cohort.

BACKGROUND: Crohn's disease (CD) is increasing in incidence and prevalence in Asia, but there is a paucity of population-based studies on risk factors for surgery in Asian patients with CD. This will be useful to identify patients who may benefit from top-down treatment. This study describes the rates of abdominal surgery and identifies associated risk factors in Singaporean patients with CD. METHODS: This was a retrospective observational study. The medical records of Singaporeans diagnosed with CD from 1970 to 2013 were reviewed from 8 different hospitals in Singapore. The cumulative probability of CD-related abdominal surgery was estimated using the Kaplan-Meier method. The logistic regression model was used to assess associations between independent risk factors and surgery. RESULTS: The cohort of 430 Singaporean patients with CD included 63.5% Chinese, 11.9% Malay, and 24.7% Indians, with a male to female ratio of 1.6; median follow-up was 7.3 years (range, 2.9-13.0 yr) and median age at diagnosis 30.5 years (range, 19.5-43.7 yr). One hundred twelve patients (26.0%) required major abdominal surgery: the cumulative risk of surgery was 14.9% at 90 days, 21.2% at 5 years, 28.8% at 10 years, 38.3% at 20 years, and 50.6% at 30 years from diagnosis. Of the surgical patients, 75.0% were Chinese, 10.7% Malays, and 14.3% Indians; 21.4% underwent surgery for inflammatory disease, 40.2% for stricturing disease, and 38.4% for penetrating disease. Age at diagnosis (A2 17-40 yr, OR: 2.75, 95% confidence interval [CI], 1.14-7.76), ileal disease (L1 location, OR: 2.35, 95% CI, 1.14-5.0), stricturing (B2 OR: 6.09, 95% CI, 3.20-11.8), and penetrating behavior (B3 OR: 21.6, 95% CI, 9.0-58.8) were independent risk factors for CD-related abdominal surgery. Indian patients were less likely to require surgery (OR: 0.40, 95% CI, 0.19-0.78). CONCLUSIONS: Age at diagnosis, L1 location, B2, and B3 disease behavior are independent risk factors for abdominal surgery. Interestingly, despite a higher prevalence of CD in Indians, a smaller proportion of Indian patients required surgery. These findings suggest that both environmental and genetic factors contribute to the risk of surgery in Asian patients with CD.

Deployment of a Short, Single-Opening Endoscopic Clip Versus a Long, Reopening Endoscopic Clip in Clinical Practice.

BACKGROUND: Endoscopic clips vary in their designs and costs. Clip wastage is a common problem, and this is dependent on the success of its deployment. AIMS: The aim of this study is to compare the rates of successful deployment between two different commonly used endoscopic clips. METHODS: A single-center, retrospective study was conducted. Endoscopy reports of patients with clips deployed over 24 months were reviewed. We compared a long-pronged, reopening endoscopic clip (type A: Resolution clip; Boston Scientific, Natick, MA, USA) versus a short-pronged, single-opening clip (type B: QuickClip2; Olympus Medical Systems Corp, Japan). The main outcome was clip deployment success rate. Secondary outcomes were predictors of successful deployment, cost, and wastage. RESULTS: Of 14,690 endoscopic cases, 472 clips (171 type A and 301 type B) were deployed in 262 procedures. Type A clips had a significantly higher successful deployment rate (147/171, 86.0 %) than type B clips (221/301, 73.4 %) (p = 0.002). On multivariate analysis, variables independently associated with successful deployment included using type A clips (OR 2.07, 95 % CI 1.20-3.55; p = 0.009) and clips placed in the lower gastrointestinal tract (OR 3.48, 95 % CI 1.64-7.40; p = 0.001). The cost of using type A clips was higher than type B clips (p < 0.001). Type B clips were associated with more wastage (p = 0.049). CONCLUSIONS: Long-pronged, reopening clips (type A) have a better deployment rate than short-pronged, single-opening clips (type B). Although type A clips had less wastage, the cost per procedure was higher.

Clinics in diagnostic imaging. 159. Jejunal intussusception due to Peutz-Jeghers syndrome.

A 21-year-old woman presented with acute onset of upper abdominal pain. A diagnosis of Peutz-Jeghers syndrome (PJS) was made based on the clinical picture of perioral pigmentation with imaging findings of transient jejunojejunal intussusceptions and small bowel polyps, and confirmed by characteristic histopathological appearances of Peutz-Jeghers polyps. PJS is a rare hereditary condition characterised by unique hamartomatous polyps, perioral mucocutaneous pigmentations, and increased susceptibility to gastrointestinal and extraintestinal neoplasms. Patients usually present with recurrent abdominal pain due to intussusception caused by polyps. Other modes of presentations include rectal bleeding and melaena. We describe the imaging findings of PJS and provide a brief review of bowel polyposis syndromes. The latter are relatively rare disorders characterised by multiple polyps in the large or small intestine, with associated risk of malignancies and other extraintestinal manifestations. Awareness of the manifestations and early diagnosis of these syndromes is crucial to prevent further complications.

Clinics in diagnostic imaging. 158. Duodenal ectopic pancreas.

A 46-year-old man presented with right loin tenderness following a road traffic accident. Computed tomography and magnetic resonance imaging showed a well-defined, smooth, enhancing oval lesion in the wall of the first part of the duodenum. The lesion was seen separately from the normal pancreas. It showed attenuation, intensity and enhancement similar to that of normal pancreas. Based on the imaging appearance, a diagnosis of ectopic pancreas was made. The patient underwent oesophagogastroduodenoscopy, endoscopic ultrasonography and fine-needle aspiration cytology of the lesion, which confirmed ectopic pancreatic tissue. Since the patient was asymptomatic, surgical resection was deferred. The embryologic origin, various locations, imaging appearance and clinical significance of ectopic pancreas are discussed.

Feasibility and efficiency of a new 22G core needle: a prospective comparison study.

BACKGROUND AND STUDY AIMS: Histological examination of core tissue samples may have advantages over cytology in endoscopic ultrasound (EUS)-guided sampling. We aimed to evaluate the feasibility and efficiency of a new 22G core biopsy needle. PATIENTS AND METHODS: Consecutive patients with a pancreatic mass lesion or peri-intestinal lymphadenopathy sequentially underwent fine needle biopsy with both a newly developed 22G core needle (the FNB needle) and a standard 22G fine needle aspiration (FNA) needle, in randomized order. RESULTS: In 144 patients, mean age 48 years (± standard deviation [SD] 14; range 18 - 82), with 145 lesions (mean lesion size 39 ± 15 mm, range 15 - 99), EUS-guided sampling was technically feasible with both needles in all patients. Mean number of passes to obtain sufficient tissue was 1.2 ± 0.5 with the core needle vs. 2.5 ± 0.9 with the standard needle (P < 0.001). FNB specimens were adequate for evaluation in 125 (86.2 %) vs. 127 (87.6 %) with FNA (P = 0.72). Among 139 patients available for follow-up, FNB provided a correct diagnosis in 110 (79.1 %) and FNA in 112 (80.6 %) (P = 0.73). Sensitivity, specificity, positive and negative predictive values, and accuracy for diagnosis of malignancy were 90 %, 100 %, 100 %, 93 %, 96 % for FNB and 77 %, 100 %, 100 %, 85 %, 92 % for FNA, respectively (P > 0.05). CONCLUSION: FNB with the new 22G core needle was technically feasible, efficient and comparable to FNA with a standard needle. The core needle required fewer passes to provide an adequate sample, offering potentially shorter procedure time.

Evidence-based approach to dyspepsia: from Helicobacter pylori to functional disease.

Patients with dyspepsia may present with associated complaints of abdominal pain, bloating, fullness, acid reflux, and epigastric tenderness on examination. The evaluation of patients with dyspepsia includes taking a comprehensive history and performing a physical examination. Although taking a patient history has its limitations in making an accurate diagnosis, it is useful in guiding the selection of subsequent diagnostic tests. Differential diagnoses of dyspepsia are best addressed using an anatomical approach. Patients with chronic dyspepsia lasting > 1 month should be evaluated for the presence of alarm features. Alarm features mandate an upper gastrointestinal endoscopy examination, as these may be suggestive of a malignancy. In patients without alarm features, a Helicobacter pylori test-and-treat strategy is cost-effective if the prevalence of H. pylori infection is high. Tests for H. pylori infection can be divided into non-invasive and minimally invasive tests. Many different antibiotic combination therapies (eg, triple therapy, quadruple therapy, levofloxacin-based therapy, sequential therapy, concomitant therapy, and probiotics with eradication therapy) are now available for the eradication of H. pylori infection. In patients who are symptomatic without an organic pathology, functional dyspepsia and other causes of abdominal pain need to be considered. Functional dyspepsia is best managed using a multifaceted approach by establishing a good physician-patient relationship, dietary and lifestyle interventions, medical therapy, psychotherapy, and the use of psychotropic medications. This review rationalizes the current-day recommendations for the evaluation and management of patients with dyspepsia in a clinical setting.

The diagnostic accuracy and strength of agreement between endoscopic ultrasound and histopathology in the staging of ampullary tumors.

AIM: Ampullary tumors are rare. Reports on ampullary tumor staging are heterogeneous and combine both periampullary and ampullary tumors. This study assessed the performance of endoscopic ultrasound (EUS) in the local staging of ampullary tumors only. METHODS: Data were collected retrospectively. We included patients with an ampullary tumor who underwent EUS and surgical resection. Tumor (T) and nodal (N) TNM staging for EUS and histopathological (HP) staging were compared. RESULTS: From 2009 to 2010, a total of 79 patients with ampullary tumors were identified. Of these, 26 had both EUS and Whipple's surgery and were included (28 did not undergo resection, 13 had palliative surgery only and 12 had resection without EUS). For T staging by HP, there were 2 (7.7 %) T1, 11 (42.3 %) T2, 12 (46.2 %) T3 and 1 (3.8 %) T4 tumors. The accuracy of EUS T staging was 73.1 % with a Kappa value of 0.564 (p < 0.0001). The sensitivity, specificity, positive predictive value (PPV), negative predictive values (NPV) of EUS, respectively were 50.0 %, 91.7 %, 33.3 % and 95.7 % for T1 tumors; 81.8 %, 80.0 %, 75.0 % and 85.7 % for T2; 75.0 %, 92.9 %, 90.0 % and 81.3 % for T3 tumors. For N staging by HP, 17 (65.4 %) were N0 and 9 (34.6 %) N1. The N staging diagnostic accuracy was 80.8 % with a Kappa value of 0.586 (p = 0.003). The sensitivity, specificity, PPV, NPV for N0 disease were 82.4 %, 77.8 %, 87.5 % and 70.0 %, respectively while for N1 they were 77.8 %, 82.4 %, 70.0 % and 87.5 %, respectively. CONCLUSIONS: EUS had a moderate strength of agreement with histopathology for both T and N staging, and a high diagnostic accuracy for nodal staging.

Endoscopic ultrasound guided fine-needle aspiration of lymph nodes and solid masses: factors influencing the cellularity and adequacy of the aspirate.

GOALS: To study the factors that influence the cellularity and adequacy of endoscopic ultrasound (EUS)-guided fine-needle aspiration (FNA). BACKGROUND: An on-site cytopathology service is preferred during EUS-guided FNA. However, this is not always available. Factors that influence the aspirate cellularity and adequacy have not been well defined in the absence of on-site cytopathology. STUDY: EUS-guided FNA procedures without an on-site cytopathologist from a single center were retrospectively studied. FNA of solid masses and lymph nodes (LN) were included. The FNA cellularity, hemorrhagic content, and endoscopists' assessment of adequacy were analyzed. RESULTS: A total of 166 patients from January 2009 to October 2010 were included. A total of 520 FNA passes were performed. Of the 166 lesions, 70 (42.2%) were solid masses and 96 (57.8%) were LNs. A 22-G needle was used in 72.3% and 25 G in 27.7% of the patients. The median (range) number of FNA passes was 3 (1 to 7) for LNs and 3 (1 to 5) for solid masses. With this, the endoscopists had an accuracy of 92.2% (153/166) for obtaining an adequate aspirate. Of the 166 samples, 4 (2.4%) were acellular, 20 (12.0%) sparsely cellular, 52 (31.4%) moderately cellular, and 90 (54.2%) highly cellular. The 25-G needle had significantly more adequate aspirates than the 22-G needle for solid masses (P=0.011). Also, increasing passes correlated with higher cellularity (P=0.002) and an adequate aspirate (P=0.021). No correlation was found for LN FNA. Lesion size did not influence the cellularity or adequacy (P>0.05). The degree of hemorrhage was not influenced by the needle gauge, number of passes, or lesion size. The diagnostic yield was not affected by hemorrhage in the sample (P>0.05). CONCLUSIONS: EUS-guided FNA obtains a high proportion of adequate aspirates for LNs and solid masses, even without an on-site cytopathologist. Small proportions of inadequate samples still occur. For solid masses, a 25-G needle with at least 3 passes is more likely to provide an adequate aspirate than a 22-G needle and fewer passes. Hemorrhage did not affect the cytopathology's ability to make a diagnosis.

Achalasia cardia with esophageal varix managed with endoscopic ultrasound-guided botulinum toxin injection.

Achalasia cardia is a motility disorder of the esophagus characterized by failure of relaxation of the lower esophageal sphincter. Nitrates and calcium channel blockers, pneumatic dilatation, botulinum toxin injection and surgical myotomy have been described in literature as possible management options. We present a patient who presented with achalasia and was co-incidentally diagnosed to have cryptogenic cirrhosis with portal hypertension and had esophageal varices. This clinical combination precluded the use of pneumatic dilatation and surgical myotomy. We injected botulinum toxin into the lower esophageal sphincter using a celiac plexus neurolysis needle under endoscopic ultrasound guidance; the clinical response was good.

An unusual cause of 'ptosis'.

A 29-year-old man with a history of dental restoration procedure was referred for a left Bell's palsy. At the emergency department, he complained instead of deteriorating unilateral ptosis and dysphagia. Incidentally, trismus was also noted. He was diagnosed with cephalic tetanus, which rapidly progressed to generalized tetanus. Ptosis is an unusual presenting complaint of tetanus. In this case, we attempt to explain how facial weakness, ptosis, and cephalic tetanus are all related. We also highlight the key aspects of tetanus in relation to the emergency physician.

Validation of the English version of the Asthma Quality of Life Questionnaire in a multi-ethnic Asian population.

The purpose of study was to assess the validity, reliability and acceptability of the English version of the Asthma Quality of Life Questionnaire in a multi-ethnic Asian population. The English version of the Standardized Asthma Quality of Life Questionnaire (AQLQ-S) and the Asthma Control Questionnaire (ACQ) were self-completed by 119 English-speaking Chinese, Malay and Indian asthmatic subjects, aged 17-78. Spirometric measurements, peak expiratory flow rate, current clinical symptoms and treatment requirements were documented. Reliability and responsiveness were analyzed in a subgroup of 57 patients who were reassessed 6 weeks later. The Cronbach alpha reliability coefficient for internal consistency of the AQLQ-S was 0.97 (0.96-0.98) for the overall score. The intraclass correlation coefficient (ICC) overall score was 0.97 (95% CI: 0.94-0.99) while the responsiveness index was 1.29 with strong longitudinal validity for clinical and spirometric measures of asthma severity and asthma control score (p < 0.001). The results of this study showed that the English version of the AQLQ-S is a sensitive and valid instrument for measuring health-related quality of life in asthmatic subjects from a multi-ethnic Asian population.