Association between Vitamin D Receptor Single-Nucleotide Polymorphisms and Colorectal Cancer in the Thai Population: A Case-Control Study.

Vitamin D and its cognate intracellular nuclear receptor, namely, vitamin D receptor (VDR), are involved in the regulation of a variety of body metabolic processes, immune function, and oncogenesis. A large number of studies demonstrated the association of low vitamin D levels and variations in five common single nucleotide polymorphisms (SNPs), FokI, BsmI, Tru9I, ApaI, and TaqI, with the risk of several cancers, including colorectal cancers. However, these associations vary among different populations. This case-control study was aimed at analysing whether common single-nucleotide polymorphisms (SNPs) and haplotypes of the vitamin D receptor (VDR) gene contribute to colorectal carcinogenesis in the Thai population. We enrolled 364 Thai participants from King Chulalongkorn Memorial Hospital between 2014 and 2015. Half of the participants underwent colonoscopy and showed a normal colon without polyps (control group) and another half were newly diagnosed patients with colorectal cancer (CRC) by colonoscopy during the index period, were under treatment, or were followed up at the outpatient clinic (case group). Differences in allele and genotype frequencies of five common VDR SNPs, between the case and control groups, were the primary outcome measures. Differences in haplotype frequencies of the five SNPs between the case and control groups were the secondary outcome measures. Among the 364 participants, baseline characteristics were not significantly different between the case and control groups, except for the higher proportion of males in the CRC group. The mean vitamin D level was also not significantly different between the case and control groups (24.6 ± 9.1 vs. 25.3 ± 10.6 ng/mL, p = 0.52). None of the five VDR SNPs was associated with CRC development (p > 0.05). However, haplotype analysis of these polymorphisms demonstrated that the AGGT haplotype was associated with a decreased risk of CRC (odds ratio 0.24, 95% confidence interval 0.07-0.81, p = 0.01). The AGGT haplotype was associated with a lower risk of CRC in the Thai population. This genetic linkage might support the role of vitamin D in colorectal carcinogenesis. However, this finding requires further study within a larger population and a multivariate analysis of other established risk factors.

Identification of Pancreatic Cancer in Biliary Obstruction Patients by FRY Site-specific Methylation.

BACKGROUND: Methylation at cg 16941656 of FRY is exclusively found in normal pancreatic tissue and has been proven to be specific for pancreatic-in-origin among several adenocarcinomas. Here, we investigated methylated DNA in the bile as a biomarker to differentiate the cause of obstruction between pancreatic cancer and benign causes. MATERIALS AND METHODS: Bile samples of 45 patients with obstructive jaundice who underwent ERCP were collected and classified into pancreatic cancer (group 1) and benign causes (group 2) in 24 and 21 patients, respectively. DNA was extracted from bile and bisul te modification was performed. After, methylation in cg 16941656 of FRY was identified by real-time PCR, with beta-actin used as a positive control. RESULTS: Methylated DNA was identified in 10/24 (41.67%) and 1/21 (4.8%) of cases in groups 1 and 2, respectively (P= 0.012). The sensitivity, specificity, positive predictive value and negative predictive value to differentiate pancreatic cancer from benign causes were 42%, 95%, 91%, and 59%, respectively. CONCLUSIONS: Detecting a methylation at cg 16941656 of FRY in bile has high specificity, with an acceptable positive likelihood rate, and may therefore be helpful in distinguishing pancreatic cancer from benign strictures.

Cocktail sedation containing propofol versus conventional sedation for ERCP: a prospective, randomized controlled study.

BACKGROUND: ERCP practically requires moderate to deep sedation controlled by a combination of benzodiazepine and opiod. Propofol as a sole agent may cause oversedation. A combination (cocktail) of infused propofol, meperidine, and midazolam can reduce the dosage of propofol and we hypothesized that it might decrease the risk of oversedation. We prospectively compare the efficacy, recovery time, patient satisfactory, and side effects between cocktail and conventional sedations in patients undergoing ERCP. METHODS: ERCP patients were randomized into 2 groups; the cocktail group (n = 103) and the controls (n = 102). For induction, a combination of 25 mg of meperidine and 2.5 mg of midazolam were administered in both groups. In the cocktail group, a bolus dose of propofol 1 mg/kg was administered and continuously infused. In the controls, 25 mg of meperidine or 2.5 mg/kg of midazolam were titrated to maintain the level of sedation. RESULTS: In the cocktail group, the average administration rate of propofol was 6.2 mg/kg/hr. In the control group; average weight base dosage of meperidine and midazolam were 1.03 mg/kg and 0.12 mg/kg, respectively. Recovery times and patients' satisfaction scores in the cocktail and control groups were 9.67 minutes and 12.89 minutes (P = 0.045), 93.1and 87.6 (P <0.001), respectively. Desaturation rates in the cocktail and conventional groups were 58.3% and 31.4% (P <0.001), respectively. All desaturations were corrected with temporary oxygen supplementation without the need for scope removal. CONCLUSIONS: Cocktail sedation containing propofol provides faster recovery time and better patients' satisfaction for patients undergoing ERCP. However, mild degree of desaturation may still develop. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01540084.

Success rate and cannulation time between precut sphincterotomy and double-guidewire technique in truly difficult biliary cannulation.

BACKGROUND AND AIM: Precut sphincterotomy (PS) is usually indicated in failed standard biliary cannulation (BC). PS requires experienced endoscopists, and contains significant risk. Double-guidewire (DG) cannulation seems to be easier, and might be useful after failed standard BC. We aimed to compare cannulation time, success rate, and complication rates between the two techniques. METHODS: Patients who failed standard BC within 10 min by the expert were defined as truly difficult BC and randomized into both groups. In the DG group, the first guidewire was left in the pancreatic duct, and then a catheter, pre-inserted with another guidewire, was used for the BC. In the PS group, a fistulotomy technique was used. RESULTS: From June 2008 to October 2009, 534 patients underwent endoscopic retrograde cholangiopancreatography. Forty-four patients (8.2%) who failed standard BC were randomized into the DG group (n = 23) and the PS group (n = 21). Median cannulation times and success rates in the DG and PS groups were 172 versus 394 s (P < 0.001), and 73.9% versus 80.9% (P = 0.724), respectively. The pancreatitis rate and serum amylase at 24 h in the DG and PS groups were 21.7% versus 14.3% (P = 0.701) and 937 versus 195 mg/dL (P = 0.020), respectively. Two from each group developed mild bleeding. No perforation occurred. CONCLUSION: In truly difficult BC, the DG technique requires a significant shorter duration for BC, with a comparable success rate to the PS technique. The post-procedure serum amylase level in the DG group was significantly higher, and there was a trend of more pancreatitis.

Non-sequential narrow band imaging for targeted biopsy and monitoring of gastric intestinal metaplasia.

AIM: To evaluate the efficacy of non-sequential narrow band imaging (NBI) for a better recognition of gastric intestinal metaplasia (GIM). METHODS: Previously diagnosed GIM patients underwent targeted biopsy from areas with and without GIM, as indicated by NBI, twice at an interval of 1 year. The authors compared the endoscopic criteria such as light blue crest (LBC), villous pattern (VP), and large long crest (LLC) with standard histology. The results from two surveillance endoscopies were compared with histology results for sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and likelihood ratio of positive test (LR+). The number of early gastric cancer cases detected was also reported. RESULTS: NBI targeted biopsy was performed in 38 and 26 patients during the first and second surveillance endoscopies, respectively. There were 2 early gastric cancers detected in the first endoscopy. No cancer was detected from the second study. Surgical and endoscopic resections were successfully performed in each patient. Sensitivity, specificity, PPV, NPV, and LR+ of all 3 endoscopic criteria during the first/second surveillance were 78.8%/91.3%, 82.5%/89.1%, 72.8%/77.8%, 86.8%/96.1, and 4.51/8.4, respectively. LBC provided the highest LR+ over VP and LLC. CONCLUSION: Non-sequential NBI is useful for GIM targeted biopsy. LBC provides the most sensitive reading. However, the optimal duration between two surveillance requires further study.

Stent-in-stent through a side hole to prevent biliary metallicstent migration.

The covered self-expandable metallic stent (SEMS) has been developed to overcome the problem of tissue in-growth, However, stent migration is a well-known com--plication of covered SEMS placement. Use of a double pigtail stent to lock the movement of the SEMS and prevent migration has been advised by many ex-perts. Unfortunately, in our case this technique led to an in-cidental upward migration of the SEMS. We used APC to create a side hole in the SEMS for plastic stent insertion as stent-in-stent. This led to a successful pre-ven-tion of stent migration.

Propofol infusion versus intermittent meperidine and midazolam injection for conscious sedation in ERCP.

BACKGROUND AND AIM: ERCP generally requires longer time than standard endoscopy. Only few studies have shown benefit of intermittent propofol over conventional sedation. This study was conducted to compare satisfaction, recovery score, and recovery/safety profiles for ERCP sedation between continuous infusion of propofol and conventional sedation. PATIENTS AND METHODS: One hundred thirty-four patients with ASA I-III underwent ERCP and were randomly assigned into two groups (n=67 each). Patients underwent propofol sedation or meperidine/midazolam sedation. Supplemental oxygen was offered only when oxygen saturation was lower than 90 %. Oxygen saturation, blood pressure, heart rate, recovery score, times for recovery and satisfaction score after procedure were recorded and analyzed. RESULTS: Average amount of meperidine, midazolam and propofol per each patient were 61.54 (+/- 27.29), 7.80 (+/- 3.73), 299.90 (+/- 146.15) mg, respectively. Time to regain full consciousness in the propofol arm was significantly shorter than in the conventional arm (17.24 +/- 5.99 versus 34.25 +/- 16.06 min, p<0.001). The rates of desaturation, bradycardia and hypotension in both arms were low and comparable. Propofol provided higher level of recovery scores at 15, 30, 45 and 60 min after the procedure (p < 0.001). CONCLUSION: Continuous infusion of propofol for ERCP by direction of gastroenterologist yields no difference in the completion rate and adverse profiles when compared with conventional technique but it provides a better recovery profile. The maintainance of appropriate level of sedation by well trained personnel is the key to achieve this success.