Pemafibrate, a novel selective PPARα modulator, attenuates tamoxifen-induced fatty liver disease.

Estrogen receptor (ER) antagonists, such as tamoxifen and toremifene, are widely used as adjuvant therapies for ER-positive breast cancer. These agents sometimes cause hepatosteatosis and steatohepatitis and it is problematic whether these agents should be withdrawn due to fatty liver disease and liver dysfunction. We herein describe a patient with fatty liver disease and hypertriglyceridemia during tamoxifen treatment, which significantly improved by adding pemafibrate, a novel PPARα activator designated as a selective PPARα modulator. Serial analysis during pemafibrate treatment revealed significant increases in circulating ketone bodies, which are indicators of hepatic fatty acid (FA) ß-oxidation. As far as we know, this is the first report demonstrating the beneficial effect of pemafibrate on tamoxifen-induced fatty liver disease, which is likely due to enhanced hepatic FA ß-oxidation by PPARα stimulation. Future large-scale studies will be needed to verify the current observation.

Risk of Gastrointestinal Endoscopic Procedure-Related Bleeding in Patients With or Without Continued Antithrombotic Therapy.

BACKGROUND: Prospective studies on bleeding risk during/after gastrointestinal endoscopic procedures are rare. AIM: We investigated the risk of endoscopic procedure-related bleeding in patients with biopsy and/or cold snare polypectomy (CSP) in relation to antithrombotic therapy. METHODS: This prospective, observational single-center cohort study (NCT02594813) enrolled consecutive patients who underwent diagnostic esophagogastroduodenoscopy (EGD) or colonoscopy. The primary outcome measure was delayed bleeding in patients with biopsy and/or CSP who required endoscopic treatment within 2 weeks post-procedure. The secondary outcomes were immediate bleeding and the number of hemostatic clips used during the procedure. RESULTS: From November 2015 to October 2018 at our institution, 3069 (mean age, 66 years) and 37,887 (57 years) patients underwent EGD with and without antithrombotic therapy, respectively. In addition, 1116 (72 years) and 11,901 (65 years) patients had colonoscopy with and without antithrombotic therapy, respectively. In the 3069 EGD patients receiving antithrombotic therapy, no delayed bleeding occurred, whereas immediate bleeding occurred in 9 of 141 patients (6.4%) with biopsy. Of the 1116 colonoscopy patients receiving antithrombotic therapy, delayed bleeding occurred in three of 228 (1.3%) following CSP. Immediate bleeding occurred in nine of 225 (4%) following biopsy and in 32 of 228 (14%) following CSP. Multivariate analysis following univariate analysis identified chronic kidney disease and CSP as factors significantly associated with procedure-related bleeding in patients taking antithrombotic agents. CONCLUSION: The risk of delayed bleeding in diagnostic EGD with biopsy or in colonoscopy with biopsy and/or CSP was low despite continuation of antithrombotic therapy.

Non-alcoholic fatty liver disease later diagnosed as myotonic dystrophy.

BACKGROUND: Myotonic dystrophy (MD) is sometimes accompanied by metabolic/endocrine disorders, including dyslipidemia, central obesity, and hypogonadism. Due to considerable individual differences in the severity and progression of myopathy, MD patients with minimal-to-mild muscle symptoms might be followed as having other diseases, such as non-alcoholic fatty liver disease (NAFLD). CASE SUMMARY: A 40-year-old non-obese man without a history of regular ethanol consumption was referred to our hospital due to persistent liver dysfunction and hyperlipidemia. His body mass index was 23.4 kg/m2. Liver histology demonstrated macrovesicular steatosis, ballooned hepatocytes with eosinophilic inclusion bodies, and perisinusoidal fibrosis, leading to the diagnosis of non-alcoholic steatohepatitis (NASH). Although he had no discernable muscle pain or weakness, persistently high serum creatine kinase (CK) and myoglobin levels as well as the presence of frontal baldness, a hatched face, history of cataract surgery, and grip myotonia indicated the possibility of MD. Southern blotting of the patient's DNA revealed the presence of CTG repeats, confirming the diagnosis. CONCLUSION: When gastroenterologists encounter NAFLD/NASH patients, serum CK should be verified. If hyperCKemia, frontal baldness, a hatched face, history of cataract surgery, and grip myotonia are noted, the possibility of MD may be considered.

Safety and Effectiveness of Nurse-Administered Propofol Sedation in Outpatients Undergoing Gastrointestinal Endoscopy.

BACKGROUND & AIMS: Esophagogastroduodenoscopy (EGD) and colonoscopy are common outpatient gastrointestinal endoscopic procedures that frequently use sedation. We aimed to identify a protocol that combines safety with cost effectiveness. METHODS: We collected data from consecutive outpatients (age, 20-98 y) who underwent diagnostic EGD (n = 117,661) or colonoscopy (n = 32,550) with propofol sedation from January 2006 through December 2016. Propofol was administered by a nurse via bolus injection using an age-adjusted standard protocol, up to a total of 200 mg. The primary outcome measure was occurrence of adverse events within 24 hours. Secondary outcome measures included rates of procedure success, respiratory depression, and other procedure-related adverse events. RESULTS: The median dose of propofol administered for EGD was 77 mg (range, 20-160 mg) and for colonoscopy was 99 mg (range, 40-200 mg). Among patients undergoing EGD, those younger than 41 years required 1.5-fold more propofol than patients 61-80 years old. The only adverse event was the transient need for supplemental oxygen supply, required by 1950 patients (1.3%): 1689 undergoing EGD (1.4%) and 261 undergoing colonoscopy (0.8%). Patients were discharged after 60 minutes and at least 66,250 patients (44%) drove themselves from the hospital. None experienced a traffic accident within 24 hours after receiving propofol sedation. CONCLUSIONS: Nurse-administered propofol monosedation using an age-adjusted standard protocol up to a maximal of 200 mg is safe and practical for outpatient gastrointestinal endoscopy.

Comparison of newly found polyps after removal of small colorectal polyps with cold or hot snare polypectomy.

BACKGROUND AND STUDY AIMS: There are limited data regarding polyp recurrence following cold or hot snare polypectomy for small colorectal polyps. The aim of this study was to evaluate the prevalence of newly found polyp after cold or hot snare polypectomy and the predictive factors. PATIENTS AND METHODS: This was a retrospective case-control study at a single municipal hospital. Patients undergoing cold or hot snare polypectomy for colorectal polyps≤8 mm included in a previous study (Digestion 2011; 84:78) were enrolled. Newly found polyps were defined as polyps detected at follow-up colonoscopy within 3 years. Predictive factors for new polyps were assessed by multivariate analysis using logistic regression. RESULTS: A total of 72 patients (female 22, mean age 68) with 184 polyps were enrolled. Eighty-nine polyps (mean size±SD, 5.3±2 mm) were resected with cold snare while 95 polyps (mean size 5.5±6 mm) were resected with hot snare polypectomy. Twenty-four new polyps (<5 mm) were found at follow-up. No polypectomy scars were detected in the vicinity of the new polyps. The prevalence of new polyps was similar (i.e., cold vs. hot snare polypectomy; 23% vs. 19%, P=0.68). Multivariate analysis revealed that the removal of ≥4 polyps was an independent predictor associated with new polyps (odds ratio:7.8, 95% confidence interval: 2.1-32, P=0.0022). CONCLUSIONS: Diminutive polyps were newly found with similar prevalence after cold or hot snare polypectomy, but there were no recurrent polyps detected.

Biliary stenting as alternative therapy to stone clearance in elderly patients with bile duct stones. .

BACKGROUND AND STUDY AIMS: Endoscopic retrograde cholangio- pancreatography with stone retrieval following endoscopic sphinc- terotomy (ES) is the standard method for the management of cho- ledocholithiasis. However, biliary stenting is used to treat patients with endoscopically irretrievable bile duct stones, especially elderly and high-risk patients. The aim of this study was to evaluate the benefits and risks of biliary stenting versus stone clearance follow- ing ES in the management of choledocholithiasis. PATIENTS AND METHODS: Between January 2010 and December 2012, 165 patients with common bile duct stones who underwent biliary stenting or stone clearance following ES were enrolled. One 7 Fr. double-pigtail plastic stent was placed without ES or stone extraction. The procedure time, hospitalization period, adverse events, additional endoscopic interventions required and one-year mortality were evaluated retrospectively. RESULTS: Ninety-nine and 66 patients were included in stenting group and in stone clearance group, respectively. Except for age, number of stones, and use of antithrombotic agents in the stent group, there were no statistically significant difference between groups. The average procedure time and hospitalization period in the stenting group were significantly shorter than those in stone clearance group (mean 21 min vs. 43.9 min, P < 0.0001; 3.8 days vs. 6.5 days, P < 0.0001). No significant differences were seen in ad- verse events and additional endoscopic interventions required be- tween both groups for at least a 1.5-year follow-up. No one-year mortality occurred. CONCLUSIONS: Biliary stenting using a double-pigtail stent proved to be a useful alternative therapy to stone clearance following ES in the management of choledocholithiasis in elderly patients.

Benefits and limitations of cap-fitted colonoscopy in screening colonoscopy.

BACKGROUND: Colonoscopy is widely used to detect colorectal cancer and to remove precancerous lesions to reduce the risk of colonic cancer. AIMS: To examine the benefits and limitations of cap-fitted colonoscopy compared to conventional colonoscopy in terms of technical performance and colorectal adenoma detection rate. METHODS: Screening colonoscopies performed from 2009 to 2010 with or without a transparent cap were retrospectively examined to compare the rate of successful intubation, cecal intubation time, and number, size, shape, and location of adenomas detected. An inclusion criterion was visualization of >95 % of the right colon. RESULTS: Data from 2,301 colonoscopies (1,165 with cap-fitted colonoscopy, 1,136 without the transparent cap) were retrospectively analyzed. Procedures were performed by four experienced endoscopists. The subjects' demographic characteristics and technical performances were similar between the two methods. The only significant difference in the technical performance between the two techniques was a shorter cecal intubation time with cap-fitted colonoscopy (5.3 vs. 6.6 min; p = 0.045) by one endoscopist. The total number of adenomas detected was significantly higher with cap-fitted colonoscopy than without the cap (586 vs. 484, respectively; p < 0.0001). Adenoma detection with cap-fitted endoscopy was significantly higher in the right colon than in the left colon (19 vs. 12 %, respectively; p = 0.0001). CONCLUSION: Cap-fitted colonoscopy did not improve the technical aspects of colonoscopy but significantly increased adenoma detection, especially in the right colon. It did not increase the detection rate of flat or depressed adenomas.

Safety and effectiveness of propofol sedation during and after outpatient colonoscopy.

AIM: To study the safety and effectiveness of propofol sedation for outpatient colonoscopy. METHODS: Propofol was given by bolus injection with an age-adjusted standard protocol consisting of 60 mg for patients < 70 years old, 40 mg for patients age 70-89 years, and 20 mg for those ≥ 90 years, and additional injections of 20 mg propofol were given up to a maximum of 200 mg. The principal parameters were the occurrence of adverse events within 24 h after colonoscopy and overall satisfaction for this procedure. Secondary parameters included successful procedure, respiratory depression, and other complications. RESULTS: Consecutive patients were entered prospectively and all 2101 entered successfully completed outpatient colonoscopy. The mean dose of propofol used was 96.4 mg (range 40-200 mg). Younger patients required higher doses of propofol than older patients (20-40 years vs ≥ 61 years: 115.3 ± 32 mg vs 89.7 ± 21 mg, P < 0.001). Transient supplemental oxygen supply was needed by five patients (0.2%); no other complications occurred. The questionnaires were completed by 1820 (87%) of 2101 patients and most rated their overall satisfaction as excellent (80%) or good (17%). The majority (65%) of patients drove home or to their office after their colonoscopy. Most (99%) were willing to repeat the same procedure. No incidents occurred within 24 h after colonoscopy. CONCLUSION: Propofol sedation using a dose < 200 mg proved both safe and practical for outpatient colonoscopy.

Prospective randomized comparison of cold snare polypectomy and conventional polypectomy for small colorectal polyps.

BACKGROUND AND AIM: The ideal method to remove small colorectal polyps is unknown. We compared removal by colon snare transection without electrocautery (cold snare polypectomy) with conventional electrocautery snare polypectomy (hot polypectomy) in terms of procedure duration, difficulty in retrieving polyps, bleeding, and post-polypectomy symptoms. METHODS: Patients with colorectal polyps up to 8 mm in diameter were randomized to polypectomy by cold snare technique (cold group) or conventional polypectomy (conventional group). The principal outcome measures were abdominal symptoms within 2 weeks after polypectomy. Secondary outcome measures were the rates of retrieval of colorectal polyps and bleeding. RESULTS: Eighty patients were randomized: cold group, n = 40 (101 polyps) and conventional group, n = 40 (104 polyps). The patients' demographic characteristics and the number and size of polyps removed were similar between the two techniques. Procedure time was significantly shorter with cold polypectomy vs. conventional polypectomy (18 vs. 25 min, p < 0.0001). Complete polyp retrieval rates were identical [96% (97/101) vs. 96% (100/104)]. No bleeding requiring hemostasis occurred in either group. Abdominal symptoms shortly after polypectomy were more common with conventional polypectomy (i.e. 20%; 8/40) than with cold polypectomy (i.e. 2.5%; 1/40; p = 0.029). CONCLUSION: Cold polypectomy was superior to conventional polypectomy in terms of procedure time and post-polypectomy abdominal symptoms. The two methods were otherwise essentially identical in terms of bleeding risk and complete polyp retrieval. Cold polypectomy is therefore the preferred method for removal of small colorectal polyps.

Hood-assisted colonoscopy is more effective in detection of colorectal adenomas than narrow-band imaging.

BACKGROUND & AIMS: Colonoscopy, using either a transparent retractable extension device or narrow band imaging, is thought to improve colon adenoma detection. We compared the abilities of a transparent retractable extension device and narrow band imaging to detect colorectal adenomas. METHODS: One hundred and seven patients with colonic adenomas that were detected by traditional colonoscopy were randomly assigned to groups that underwent a second colonoscopy that used either a transparent retractable extension or narrow band imaging; adenomas were removed. The principal outcome parameters were the number, size, shape, and location of adenomas detected. The patients' demographic characteristics, indications for colonoscopy, and cecal intubation times were similar between groups. RESULTS: Use of the transparent retractable extension resulted in detection of 31% more adenomas than the initial procedure (P < .0001). The majority of newly discovered adenomas were sessile (79%; 26/33) and less than 5 mm in size (73%; 24/33). There was no significant increase in adenoma detection (5%) between first colonoscopy and second colonoscopy using narrow band imaging. Additional adenomas were found in 40.7% of patients that were examined using the transparent hood (22/54) versus 13.2% of those examined using narrow band imaging (7/53) (P = .0028). CONCLUSIONS: Colonoscopy with a transparent retractable extension significantly improved the adenoma detection rate compared with repeat colonoscopy using narrow band imaging.

Techniques and Outcomes of Endoscopic Decompression Using Transanal Drainage Tube Placement for Acute Left-sided Colorectal Obstruction.

BACKGROUND: If it is possible, endoscopic decompression for acute left-sided colorectal obstruction will be effective in critically ill patients. This study was to evaluate the techniques and outcomes of transanal drainage tube placement following urgent colonoscopy in management of acute left-sided colorectal obstruction. METHODS: From January 2000 to December 2009, 69 consecutive patients (36 males, age 38 to 94, mean = 71) were hospitalized because of acute left-sided colorectal obstruction. Urgent colonoscopy was performed within 12 hours of entry for diagnosis and treatment (mean time, 6.5 hours). Endoscopic decompression using a transanal drainage tube was attempted. Clinical success, methods used, and complications were retrospectively evaluated. RESULTS: The cause of obstruction was colorectal carcinoma in 66 patients (96%). The site of obstruction was sigmoid colon in 37 (54%), rectum in 20 (29%), and descending colon in 12 (17%). Out of 69 patients, endoscopic decompression using the transanal drainage tube was successful in 66 (96%). The use of combination of transanal drainage tube and the equipped guidewire enabled endoscopic decompression was successful in 45 patients (65%), though a small-diameter upper endoscope was used in 2 patients to introduce the guidewire beyond the obstruction. Perforation during the placement developed in 2 patients and one patient was unsuccessful. CONCLUSIONS: Transanal drainage tube placement following urgent colonoscopy was effective in the management of acute left-sided colorectal obstruction. In the majority of patients, the materials and methods used for the transanal drainage tube placement were simple and easy.

Prospective comparison between sedated high-definition oral and unsedated ultrathin transnasal esophagogastroduodenoscopy in the same subjects: pilot study.

BACKGROUND: Recently, quality as well as acceptability has been a concern regarding endoscopy. The aim of the present study was to compare the acceptability and quality of sedated high-definition esophagogastroduodenoscopy (sHD-EGD) using a newly developed high-definition videoscope with those of unsedated ultrathin esophagogastroduodenoscopy (uUT-EGD) using a 5.2 mm videoscope. METHODS: Twenty-two volunteers underwent both peroral sHD-EGD and transnasal uUT-EGD on the same day. Sedation consisted of 40 mg of propofol i.v. Both endoscopist and subject satisfaction levels were assessed using a 10 cm visual analogue scale. RESULTS: All 22 subjects completed the sHD-EGD and 21 subjects completed the uUT-EGD. The endoscopist and subject satisfaction levels of sHD-EGD were significantly better than those of uUT-EGD (overall endoscopist satisfaction: 9 vs 4, P < 0.0001; overall subject satisfaction: 9 vs 3, P < 0.0001). The optical quality of the endoscopic images of sHD-EGD was significantly higher than that of uUT-EGD except in the duodenal bulb (overall quality: 8 vs 7, P < 0.0001). The interobserver agreement for EGD findings in sHD-EGD was better than with uUT-EGD, although the EGD findings in both sHD-EGD and uUT-EGD were similar. After undergoing both procedures, 91% were willing to have sHD-EGD again compared to 9% with uUT-EGD. CONCLUSIONS: The endoscopist and subject satisfaction levels and image quality of sHD-EGD were better than those of uUT-EGD. The routine use of high-definition videoscopes would be expected to provide better acceptability than that obtained with unsedated endoscopy.

Low-dose propofol sedation for diagnostic esophagogastroduodenoscopy: results in 10,662 adults.

OBJECTIVE: The use of propofol sedation during endoscopic procedures has increased in recent years. The aim of this study was to evaluate the safety and effectiveness of nurse-administered low-dose propofol sedation for diagnostic esophagogastroduodenoscopy (EGD). METHODS: We prospectively assessed the outcome and complications of low-dose bolus propofol for endoscopic sedation for diagnostic EGD. Propofol was administered by bolus injection, with a standard protocol of 40 mg for patients <70 years old, 30 mg for patients 70-89 years old, and 20 mg for patients 90 years or older. When required for adequate sedation, additional doses were given, to a maximum of 120 mg. The primary outcome measure was respiratory depression, defined as oxygen desaturation (SpO(2) <90%) that continued for more than 20 s. Secondary measures included successful procedures, full recovery within 60 min of the procedure, and complications. RESULTS: All procedures were successful; 8,431 of 10,662 patients (79.1%) completed diagnostic EGD with a single bolus of propofol. Only 0.26% (28 patients) required transient supplemental oxygen supply; neither mask ventilation nor endotracheal intubation was required. Full recovery occurred in 99.9% of patients 60 min after the procedure. Men and younger patients required significantly higher doses of propofol than did the women and older patients (men vs. women, 46.5+/-19 vs. 42.7+/-15 mg, P=0.0008; age 40-49 vs. age 50-59, 51.5+/-16 vs. 46.3+/-13 mg, P<0.0001). Of the 400 patients, 368 (92%) wanted to drive home or to their offices, and all did so without incident. A total of 99% were willing to repeat the same procedure again. CONCLUSIONS: Low-dose nurse-administered propofol sedation is safe and practical for diagnostic EGD.

Safety and driving ability following low-dose propofol sedation.

BACKGROUND AND AIM: Automobile driving is prohibited after midazolam sedation because of the slow recovery of psychomotor function. This study prospectively assessed the safety of low-dose propofol sedation (study 1) and compared driving ability following propofol and midazolam sedation (study 2). METHODS: Study 1: We prospectively investigated bolus injection of a low-dose of propofol (40-80 mg for <70 years and 30 mg for >or=70 years) for diagnostic esophagogastroduodenoscopy (EGD). Respiratory depression, time to full recovery, and overall patient satisfaction were evaluated and blood concentrations of propofol were measured. Study 2: A subset of subjects undergoing diagnostic EGD were randomized to receive 40 mg of propofol (n = 30), 4 mg of midazolam (n = 30) or no sedation controls (n = 20), and the residual effects of each drug were tested using a driving simulator. The primary outcome measure was driving ability. The second outcome measures were overall patient satisfaction and complications. RESULTS: Study 1: Only 1.1% of 12,031 healthy subjects developed transient oxygen desaturation. Full recovery was present in 97.5% 30 min after the procedure; 99.8% were willing to repeat the same procedure. The blood levels of propofol (40-80 mg) at 60 min were <100 ng/ml. Study 2: Driving ability recovered to the basal level within 60 min of propofol administration but not with 120 min with midazolam. There were no complications; overall patient satisfaction was similar between propofol and midazolam (8.9 vs. 8.5, p = 0.34). CONCLUSION: Low-dose propofol sedation was safe and recovery including driving ability was with 60 min.

Propofol sedation for endoscopic procedures in patients 90 years of age and older.

BACKGROUND AND AIM: There are only a few studies on propofol sedation for very elderly patients. The present study was undertaken to evaluate the safety of propofol sedation in patients 90 years of age and older undergoing endoscopic procedures. METHODS: We prospectively assessed endoscopic procedures for patients 90 years of age and older using propofol sedation. Endoscopic procedures, dosage used, respiratory depression, complications and 30-day mortality were evaluated. In a subset of the enrolled patients, the blood concentrations of propofol were measured. RESULTS: All 241 patients completed endoscopic procedures. For esophagogastroduodenoscopy, percutaneous endoscopic gastrostomy, colonoscopy, and endoscopic retrograde cholangiopancreatography, the mean propofol doses used were 22, 24, 46 and 42 mg, respectively. Four patients required oxygen and 1 patient was treated by short periods of mask ventilation. There was no perforation, bleeding, pancreatitis or 30-day mortality. In diagnostic esophagogastroduodenoscopy, the level of sedation and propofol blood concentrations after administration of propofol (24 +/- 6.8 mg) in patients 90 years of age and older corresponded to those of propofol (61 +/- 13 mg) in middle-aged patients (control). CONCLUSION: Low-dose propofol sedation is safe and may be enough for patients 90 years of age and older undergoing endoscopic procedures.