Oncologic outcomes according to the location and status of resection margin in pancreas head cancer: role of radiation therapy in R1 resection.

PURPOSE: The clinical significance of margin status in pancreatic head cancer is still controversial due to the nonstandardized definition of R status and pathologic reporting. This study aims to evaluate the impact of the margin status including location and the role of radiation therapy in pancreatic head cancer. METHODS: A total of 314 patients who underwent curative-intent surgery for pancreatic head cancer between 2010 and 2017 were analyzed. Demographics, survival, and local recurrences were compared according to 2 definitions: 0-mm R1 as direct involvement and 1-mm R1 as close resection margin less than 1 mm. The specific margins were divided into 4 groups according to the location around the pancreas: pancreas transection, anterior surface, posterior surface, and vessel (superior mesenteric artery/superior mesenteric vein) margin. RESULTS: The 0-mm R1-rate was 15.6%, and increased to 36.3% in 1-mm R1. The median overall survival rate of 0-mm R0 vs. R1 was 26 months vs. 16 months (P = 0.052) and that of 1-mm R0 vs. R1 was 27 months vs. 18 months, respectively (P = 0.016). In individual margins, posterior, anterior surface, and pancreas transection margin involvement were associated with poor outcome, and the 1 mm posterior surface involvement was an independent risk factor for disease-free survival (hazard ratio, 1.63). Adjuvant radiation therapy had oncologic benefits, especially in R1 patients (P = 0.011) compared to R0 patients (P = 0.088). CONCLUSION: Margin status, especially 1-mm R1 status is an important predictive factor, and involved posterior surface has a clinical impact. Patients with positive margins should be considered adjuvant radiation therapy.

Risk stratification of patients with gastric lesions indefinite for dysplasia.

BACKGROUND/AIMS: There are no definite guidelines for the management of gastric lesions diagnosed as indefinite for dysplasia (IND) by endoscopic forceps biopsy (EFB). Therefore, this study aimed to evaluate the clinical outcomes of gastric IND and predictive factors for gastric neoplasm. METHODS: This study included 457 patients with a first diagnosis of gastric IND by EFB between January 2005 and December 2013. Patient characteristics and endoscopic and pathological data were reviewed and compared. RESULTS: Of the 457 gastric IND patients, 128 (28%) were diagnosed with invasive carcinoma, 21 (4.6%) with high-grade dysplasia, 31 (6.8%) with low-grade dysplasia, and 277 (60.6%) as negative for dysplasia. Of lesions observed, 180 (39.4%) showed upgraded histology. Multivariate analysis revealed that surface erythema (odds ratio [OR], 2.804; 95% confidence interval [CI], 1.741 to 4.516), spontaneous bleeding (OR, 2.618; 95% CI, 1.298 to 5.279), lesion size ≥ 1 cm (OR, 5.762; 95% CI, 3.459 to 9.597), and depressed morphology (OR, 2.183; 95% CI, 1.155 to 4.124) were significant risk factors for high-grade dysplasia or adenocarcinoma. The ORs associated with 2 and ≥ 3 risk factors were 7.131 and 34.86, respectively. CONCLUSION: Precautions should be taken in the management of gastric IND patients, especially when risk factors, including surface erythema, spontaneous bleeding, lesion size ≥ 1 cm, and depressed morphology are present. Considering the combined effect of the presence of multiple risk factors on the incidence of high-grade dysplasia or adenocarcinoma, endoscopic resection should be recommended if a gastric IND patient has at two or more of these factors.

Stable carbamate pathway towards organic-inorganic hybrid perovskites and aromatic imines.

Methyl ammonium methyl carbamate (MAC), formulated as CH3NH3 +CH3NHCO2 -, was synthesized by reacting liquid methylamine with supercritical CO2, and its structure was refined by single-crystal X-ray diffraction. MAC is a white crystalline salt and is as reactive as methylamine, and is a very efficient alternative to toxic methylamine. We were able to produce hybrid perovskite MAPbI3 (MA = methyl ammonium) by grinding MAC with PbI2 and I2 at room temperature, followed by storing the mixed powder. Moreover, this one-pot method is easily scalable for the large-scale synthesis of MAPbI3 in a small vessel. We have also investigated the reactivity of MAC towards aromatic aldehydes in the absence of solvent. The solventless reactions afforded imines as exclusive products with over 97% yield, which show higher selectivity than the methylamine-based synthesis. Complete conversions were typically accomplished within 3 h at 25 °C. The results of this study emphasize the importance of solid carbamates such as MAC to develop an environmentally friendly process for the synthesis of various amine-based materials on the industrial scale.

Frequency of post-tonsillectomy hemorrhage relative to time of day.

OBJECTIVES: Postoperative hemorrhage is a serious complication of tonsillectomy, with secondary bleeding rates affecting up to 0.8% to 3% of patients. Although these bleeds are anecdotally perceived as occurring more frequently at night, the occurrence of hemorrhage relative to the time of day has not been investigated. We measured the frequency of post-tonsillectomy hemorrhage onset relative to the time of day. METHODS: We reviewed electronic medical records of all patients who experienced postprocedural hemorrhage (International Classification of Disease, Ninth Edition [ICD-9] 998.11, ICD-10 J95.830 at two hospitals within a tertiary academic health system in a 10-year period). Patient demographics, time of bleed onset, emergency room [ED] arrival time, and management (operating room vs. observation) were abstracted. Patients without a recorded bleeding time were excluded. Time of bleed onset was categorized as morning (6:01 am-12 pm), afternoon (12:01 pm-6 pm), evening (6:01 pm-12 am), or overnight (12:01 am-6 am). Chi-square goodness of fit test was used to assess the distribution of hemorrhage timing (P ≤ 0.05). RESULTS: A total of 7,396 patients underwent tonsillectomy May 2008 through May 2018, among whom 121 (2%) post-tonsillectomy hemorrhage patients were identified. Among the 104 patients with ED arrival times, 29 (28%) arrived in the morning; 15 (14%) arrived in the afternoon; 40 (38%) arrived in the evening; and 20 (19%) arrived overnight (P = 0.003). Sixty patients (mean age 17.1 years, standard deviation 16.6) had a recorded timing of bleed onset. Bleed onset occurred most commonly overnight (24, 40%), followed by evening (21, 35%), afternoon (11, 18%), and morning (4, 7%) (P = 0.0007). CONCLUSION: In this cohort, post-tonsillectomy hemorrhage occurred most frequently between midnight and 6 am. Our findings confirm anecdotal experience and provide data in setting caregiver expectations. LEVEL OF EVIDENCE: 4 Laryngoscope, 130:1823-1827, 2020.

Predictive value of olfactory impairment for cognitive decline among cognitively normal adults.

OBJECTIVE: Dementia affects over 47 million people worldwide. Olfactory impairment (OI) is a well-established predictive marker of conversion to dementia among those with mild cognitive impairment. This systematic review aims to describe the predictive value of OI for future cognitive decline among cognitively normal adults. METHODS: A literature search encompassing PubMed, EMBASE, and Cochrane for longitudinal cohort studies following cognitively normal adults with baseline OI in comparison to those without OI reporting incident cognitive impairment or dementia was included. Study design, participant demographics, olfactory testing method, and incidence of cognitive decline or dementia were abstracted. Two investigators independently reviewed all articles. RESULTS: The search yielded 964 nonduplicate abstracts and titles, from which 19 full-text articles were reviewed and 10 were included. Studies included were all good quality (mean score 8.7 of 9), and all studies (100%) found a statistically significant association between baseline OI and incident cognitive decline compared with normosmic controls. CONCLUSION: The existing literature suggests that OI predicts future cognitive decline among cognitively normal adults, supporting olfactory evaluation as a low-cost, minimally invasive, and widely available screening tool to be used in combination with other tests to identify adults at early risk of dementia. LEVEL OF EVIDENCE: NA Laryngoscope, 130:840-847, 2020.

The Association of Serum Vitamin D Level With the Severity of Dry Eye Parameters in Primary Sjögren Syndrome.

PURPOSE: To analyze the relationship between serum 25(OH)D3 level and dry eye parameters in primary Sjögren syndrome (SS). METHODS: This study included 74 eyes of 74 patients diagnosed with primary SS. Dry eye parameters included tear breakup time, Schirmer I value, corneal staining score, conjunctival staining score, and Ocular Surface Disease Index. The serum concentration of 25(OH)D3 was evaluated. RESULTS: The mean serum 25(OH)D3 level was 20.4 ± 8.0 ng/mL. There were strong negative correlations between serum 25(OH)D3 level and corneal staining score (P < 0.001, r = -0.446) and conjunctival staining score (P < 0.001, r = -0.455). The Schirmer I value and tear breakup time showed significant positive correlations with serum 25(OH)D3 level (P = 0.038, r = 0.261 and P = 0.003, r = 0.352, respectively). The Ocular Surface Disease Index did not show any significant correlation with serum 25(OH)D3 level. CONCLUSIONS: This study demonstrates that serum 25(OH)D3 level might be associated with dry eye severity in primary SS.

Association Between Microvascular Retinal Signs and Age-Related Hearing Loss in the Atherosclerosis Risk in Communities Neurocognitive Study (ARIC-NCS).

Importance: Given that age-related hearing loss is highly prevalent and treatable, understanding its causes may have implications for disease prevention. Objective: To investigate whether microvascular retinal signs are associated with age-related hearing loss attributable to a hypothesized underlying shared pathologic entity involving microvascular disease. Design, Setting, and Participants: The Atherosclerosis Risk in Communities Neurocognitive Study (ARIC-NCS) is a community-based prospective cohort study of 15 792 men and women aged 45 to 64 years at baseline. The ARIC-NCS participants returned for a fifth clinic visit in 2011-2013 and a sixth clinic visit in 2016-2017. Participants were recruited from 4 US communities (Washington County, Maryland; Forsyth County, North Carolina; Jackson, Mississippi; and Minneapolis suburbs, Minnesota). Participants included a subset of the ARIC-NCS cohort with complete covariate data who underwent retinal fundus photography at visit 5 (2011-2013) and completed hearing assessment at visit 6 (2016-2017) (N = 1458). Overall, 453 participants had diabetes; of those, 68 had retinopathy. Of 1005 participants without diabetes, 42 had retinopathy. Exposures: Microvascular retinal signs included retinopathy, arteriovenous (AV) nicking, and generalized arteriolar narrowing measured using the central retinal arteriolar equivalent (CRAE). Main Outcomes and Measures: Hearing was measured using the better-hearing ear pure-tone average (PTA) of air conduction speech thresholds (0.5, 1, 2, and 4 kHz). Multivariable-adjusted linear and ordered logistic regression was used to estimate the association between microvascular retinal signs and age-related hearing loss to describe the precision of the estimates and provide a plausible range for the true association. Results: After full adjustment among 1458 individuals in the analytic cohort (mean [SD] age, 76.1 [5.0] years [age range, 67-90 years]; 825 women [56.6%]; 285 black [19.5%]), the difference in PTA per dB hearing level in persons with and without retinopathy was 2.21 (95% CI, -0.22 to 4.63), suggesting that retinopathy is associated with poorer hearing, although the width of the 95% CI prevents definitive conclusions about the strength of the observed association. Restricting the analysis to participants without diabetes, the difference in PTA associated with retinopathy was even greater (4.14; 95% CI, 0.10-8.17 dB hearing level), but the large width of the 95% CI prevents definitive conclusions about the association. In analyses quantifying the mean differences in hearing thresholds at individual frequencies by retinopathy status, the estimates trended toward retinopathy being associated, contrary to expectation, with better high-frequency hearing. At 8 kHz, the estimated difference in hearing thresholds in persons with retinopathy vs those without was -4.24 (95% CI, -7.39 to -1.09). Conclusions and Relevance: In this population-based study, an association between the presence of microvascular retinal signs and hearing loss was observed, suggesting that retinopathy may have the potential to identify risk for hearing loss in persons without diabetes. The precision of these estimates is low; therefore, additional epidemiologic studies are needed to better define the degree of microvascular contributions to age-related hearing loss.

The association between diabetes and olfactory impairment in adults: A systematic review and meta-analysis.

BACKGROUND: Evidence suggests that olfactory impairment (OI) may be a degenerative neurologic complication of diabetes; however, the association is not yet well established. The objective of this work was to systematically review existing literature on the association between diabetes and OI in adults, with meta-analysis of evaluable studies. METHODS: A literature search encompassing 358 abstracts from the last 75 years in PubMed, EMBASE, and Cochrane was performed. English-language articles investigating adults with diabetes and OI in comparison to control groups with original data and ≥7 subjects were included. The Newcastle-Ottawa scale was applied for quality assessment. Two investigators independently reviewed all articles. For meta-analysis, the odds ratio of OI in diabetes compared with control groups was calculated using the fixed effects model. RESULTS: The initial search yielded 358 abstracts, from which 21 articles were reviewed and 11 articles (n = 6,747) were included. Studies included were case-control (64%) or cross-sectional (36%) with evidence level 3b. On the Newcastle-Ottawa scale, the mean quality assessment score for case-control and cross-sectional studies was 7.4 (maximum of 9) and 7.0 (maximum of 10), respectively. A statistically significant association between diabetes and olfaction compared with controls was found in 6 (55%) of the 11 articles. Four studies were eligible for meta-analysis, which yielded an overall odds of having OI with diabetes as 1.58 times more likely than in control groups (95% CI [1.16, 2.16]; I 2 = 10.3%). CONCLUSIONS: The reviewed studies support a significant association between diabetes and OI. Further studies are warranted to characterize this association. LEVEL OF EVIDENCE: 3a.

Etomidate Sedation for Advanced Endoscopic Procedures.

BACKGROUND AND STUDY AIM: Although propofol is widely used for sedation for endoscopic procedures, concerns remain regarding cardiopulmonary adverse events. Etomidate has little effect on the cardiovascular and respiratory systems, but patient satisfaction analysis is lacking. We compared the efficacy and safety of balanced propofol and etomidate sedation during advanced endoscopic procedures. METHODS: As a randomized noninferiority trial, balanced endoscopic sedation was achieved using midazolam and fentanyl, and patients were randomly assigned to receive propofol (BPS) or etomidate (BES) as add-on drug. The main outcomes were sedation efficacy measured on a 10-point visual analog scale (VAS) and safety. RESULTS: In total, 186 patients (94 in the BPS group and 92 in the BES group) were evaluated. BES did not show noninferiority in terms of overall patient satisfaction, with a difference in VAS score of -0.35 (97.5 % confidence interval -1.03 to ∞, p = 0.03). Among endoscopists and nurses, BES showed noninferiority to BPS, with differences in VAS scores of 0.06 and 0.08, respectively. Incidence of cardiopulmonary adverse events was lower in the BES group (27.7 versus 14.1 %, p = 0.023). Hypoxia occurred in 5.3 and 1.1 % of patients in the BPS and BES group (p = 0.211). Myoclonus occurred in 12.1 % (11/92) in the BES group. BES had lower risk of overall cardiopulmonary adverse events (odds ratio 0.401, p = 0.018). CONCLUSIONS: BES was not noninferior to BPS in terms of patient satisfaction. However, BES showed better safety outcomes in terms of cardiopulmonary adverse events.

Reaching across the aisle: Cross-disciplinary collaboration in otolaryngology research.

OBJECTIVES: Collaboration and diversity of expertise are increasingly emphasized in the production of successful research. However, the degree of cross-disciplinary collaboration in otolaryngology research is unknown. In this study, we quantify cross-disciplinary collaboration in otolaryngology publications. METHODS: We retrospectively analyzed authorship and study characteristics for all original articles published from January 2014 to December 2016 in three key peer-reviewed otolaryngology journals: Laryngoscope, Otolaryngology-Head & Neck Surgery, and JAMA Otolaryngology-Head & Neck Surgery. Author affiliations and online searches were used to determine author's primary discipline. Subspecialty topic of article, study design, and funding sources were also recorded. Fisher exact test was used to compare characteristics of articles with and without cross-disciplinary authorship. RESULTS: A total of 2,378 articles were reviewed, of which 1,312 (55%) articles had one or more cross-disciplinary collaborators. Among articles with cross-disciplinary collaboration, the greatest representation of disciplines was from other medical specialties (1,109, 50.9%), epidemiology/biostatistics (266, 12.2%), pathology/histology (175, 8.0%), biologic sciences (168, 7.7%), and radiology/imaging (144, 6.6%). Cross-disciplinary studies had a significantly greater proportion of articles on the topic of head and neck compared to studies without collaboration (P < 0.0001). The proportion of funded studies was significantly greater among articles with collaboration compared to articles without collaboration (P < 0.0001). CONCLUSION: The majority of articles published during a 3-year period in three influential otolaryngology journals had cross-disciplinary collaboration. There is potential opportunity for further leveraging expertise, funding opportunities, and dissemination of key findings through collaborative research. LEVEL OF EVIDENCE: NA Laryngoscope, 129:1800-1805, 2019.

Comparative Secretome Profiling and Mutant Protein Identification in Metastatic Prostate Cancer Cells by Quantitative Mass Spectrometry-based Proteomics.

BACKGROUND: Secreted proteins play an important role in promoting cancer (PCa) cell migration and invasion. Proteogenomics helps elucidate the mechanism of diseases, discover therapeutic targets, and generate biomarkers for diagnosis through protein variations. MATERIALS AND METHODS: We carried out mass a spectrometry-based proteomic analysis of the conditioned media (CM) from two human prostate cancer cell lines, belonging to different metastatic sites, to identify potential metastatic and/or aggressive factors. RESULTS: We identified a total of 598 proteins, among which 561 were quantified based on proteomic analysis. Among the quantified proteins, 128 were up-regulated and 83 were down-regulated in DU145/PC3 cells. Six mutant peptides were identified in the CM of prostate cancer cell lines using proteogenomics approach. CONCLUSION: This is the first proteogenomics study in PCa aiming at exploring a new type of metastatic factor, which are mutant peptides, predicting a novel biomarker of metastatic PCa for diagnosis, prognosis and drug targeting.

Clinical Effectiveness of Submucosal Injection with Indigo Carmine Mixed Solution for Colon Endoscopic Mucosal Resection.

BACKGROUND/AIMS: Submucosal injection with indigo carmine mixed solution can improve the delineation of colorectal neoplasia during endoscopic mucosal resection (EMR). Thus, the aim of this study was to evaluate the efficacy of submucosal injection with indigo carmine mixed solution during EMR of colorectal neoplasia. METHODS: This was a prospective, randomized, controlled study of a total of 212 neoplastic colon polyps (5-20 mm) subjected to EMR in a single tertiary university hospital. The patients were randomized into two groups according to whether or not indigo carmine mixed solution was used, and the complete resection rate (CRR) after EMR was evaluated. RESULTS: A total of 212 neoplastic polyps (normal saline group, 115; indigo carmine group, 97) were successfully removed by EMR. There was no significant difference in the CRR (92.8 vs. 89.6%, p = 0.414) or macroscopic delineation (86.0 vs. 93.8%, p = 0.118) between the two groups. In a separate analysis of sessile serrated adenomas/polyps (SSAs/Ps), macroscopic delineation was better in the indigo carmine group than the normal saline group (87.5 vs. 53.8%), albeit not significantly (p = 0.103). In univariate analyses, the CRR was significantly related to polyp location, polyp morphology, macroscopic delineation, and pathologic findings. In a multiple logistic regression analysis, macroscopic delineation (odds ratio (OR), 7.616, p = 0.001) and polyp pathology (OR, 8.621; p < 0.001) were significantly associated with the CRR. CONCLUSIONS: Submucosal injection with indigo carmine mixed solution did not improve the CRR or macroscopic delineation of EMR of colorectal neoplasias.

First profiling of lysine crotonylation of myofilament proteins and ribosomal proteins in zebrafish embryos.

Zebrafish embryos are translucent and develop rapidly in individual eggs ex utero; they are widely used as models for embryogenesis and organ development for human diseases and drug discovery. Lysine crotonylation (Kcr) is a type of histone post-translational modifications discovered in 2011. Kcr dynamics are involved in gene expression regulation and acute kidney injury; however, little is known about the effects of Kcr on non-histone proteins. In the present study, we conducted the first proteome-wide profiling of Kcr in zebrafish larvae and identified 557 Kcr sites on 218 proteins, representing the Kcr event in zebrafish. We identified two types of Kcr motifs containing hydrophobic (Leu, Ile, Val) and acidic (Asp and Glu) amino acids near the modified lysine residues. Our results show that both crotonylated proteins and sites of crotonylation were evolutionarily conserved between zebrafish embryos and humans. Specifically, Kcr on ribosomal proteins and myofilament proteins, including myosin, tropomyosin and troponin, were widely enriched. Interestingly, 55 lysine crotonylation sites on myosin were distributed throughout coiled coil regions. Therefore, Kcr may regulate muscle contraction and protein synthesis. Our results provide a foundation for future studies on the effects of lysine crotonylation on aging and heart failure.

The relationship between local recurrence and positive lateral margin after en bloc resection of colorectal neoplasm.

BACKGROUND: The factors associated with recurrence of colonic neoplasm after endoscopic resection with a positive lateral margin are not well known. Thus, we evaluate the relationship between recurrence and positive lateral margin after endoscopic en bloc resection of colorectal neoplasm. METHODS: A retrospective review of 9302 patients who underwent colonic endoscopic resection from January 2008 to January 2015. Of these, a total of 76 patients with positive lateral margins with clear evidence of the its location on endoscopic picture after endoscopic en bloc resection of colorectal neoplasm (>10 mm) were included. RESULTS: Ten of 76 (13.2%) patients experienced recurrence during the follow-up period (mean f/u month, 21.7 ± 15.6). In cases with positive lateral margins, the 3- and 5-year local recurrence rate of colorectal neoplasm was 28.1% and 40.1%, respectively. The histological features of the recurrence group were as follows: one case of adenocarcinoma [from low-grade adenoma (LGA)]; two cases of high-grade adenoma (HGA) (one from HGA and one from LGA); and seven cases of LGA (four from adenocarcinoma, two from LGA, and one from HGA). The mean age of patients, locations of the lesions, and histologic type were not significantly associated with local recurrence. In multivariate Poisson regression analyses, total length of lateral margin involvement ≥8 mm (relative risk 12.51; 95% CI 1.11-140.34, p = .040) was a significant predictor of local recurrence. CONCLUSIONS: Positive lateral margins ≥8 mm may be a reliable predictor of local recurrence after endoscopic en bloc resection of colorectal neoplasm.

Mechanism Investigation of Rifampicin-Induced Liver Injury Using Comparative Toxicoproteomics in Mice.

Tuberculosis is one of the top causes of death among curable infectious diseases; it is an airborne infectious disease that killed 1.1 million people worldwide in 2010. Anti-tuberculosis drug-induced liver injury is the primary cause of drug-induced liver injury (DILI). Rifampicin is one of the most common anti-tuberculosis therapies and has well-known hepatotoxicity. To understand the mechanism of rifampicin-induced liver injury, we performed a global proteomic analysis of liver proteins by LC-MS/MS in a mouse model after the oral administration of 177 and 442.5 mg/kg rifampicin (LD10 and LD25) for 14 days. Based on the biochemical parameters in the plasma after rifampicin treatment, the hepatotoxic effect of rifampicin in the mouse liver was defined as a mixed liver injury. In the present study, we identified 1101 proteins and quantified 1038 proteins. A total of 29 and 40 proteins were up-regulated and 27 and 118 proteins were down-regulated in response to 177 and 442.5 mg/kg rifampicin, respectively. Furthermore, we performed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses to characterize the mechanism of rifampicin-induced hepatotoxicity. In the molecular function category, glutathione transferase activity was up-regulated and proteins related to arachidonic acid metabolism were down-regulated. In the KEGG pathway enrichment-based clustering analysis, the peroxisome proliferator-activated receptor-γ (PPARγ) signaling pathway, cytochrome P450, glutathione metabolism, chemical carcinogenesis, and related proteins increased dose-dependently in rifampicin-treated livers. Taken together, this study showed in-depth molecular mechanism of rifampicin-induced liver injury by comparative toxicoproteomics approach.

Partially Covered Metal Stents May Not Prolong Stent Patency Compared to Uncovered Stents in Unresectable Malignant Distal Biliary Obstruction.

BACKGROUND/AIMS: Controversy still exists regarding the benefits of covered self-expandable metal stents (SEMSs) compared to uncovered SEMSs. We aimed to compare the patency and stent-related adverse events of partially covered SEMSs (PC-SEMSs) and uncovered SEMSs in unresectable malignant distal biliary obstruction. METHODS: A total of 134 patients who received a PC-SEMS or uncovered SEMS for palliation of unresectable malignant distal biliary obstruction were reviewed retrospectively. The main outcome measures were stent patency, stent-related adverse events, and overall survival. RESULTS: The median stent patency was 118 days (range, 3 to 802 days) with PC-SEMSs and 105 days (range, 2 to 485 days) with uncovered SEMSs (p=0.718). The overall endoscopic revision rate due to stent dysfunction was 36.6% (26/71) with PC-SEMSs and 36.5% (23/63) with uncovered SEMSs (p=0.589). Tumor ingrowth was more frequent with uncovered SEMSs (4.2% vs 19.1%, p=0.013), but migration was more frequent with PC-SEMSs (11.2% vs 1.5%, p=0.04). The incidence of stent-related adverse events was 2.8% (2/71) with PC-SEMSs and 9.5% (6/63) with uncovered SEMSs (p=0.224). The median overall survival was 166 days with PC-SEMSs and 168 days with uncovered SEMSs (p=0.189). CONCLUSIONS: Compared to uncovered SEMSs, PC-SEMSs did not prolong stent patency in unresectable malignant distal biliary obstruction. Stent migration was more frequent with PC-SEMSs. However, tumor ingrowth was less frequent with PC-SEMSs compared to uncovered SEMSs.

The Efficacy of a Novel Tissue Grasper-Clips Technique for Large Perforations of the Sigmoid Colon in an Experimental Animal Model (Video).

BACKGROUND: The incidence of iatrogenic colonic perforation has been gradually increasing. In particular, sigmoid colon perforations are difficult to handle because of excess mobility. AIM: The aim of this study was to evaluate the efficacy of the twin grasper-clips technique for large perforations of the sigmoid colon. METHODS: This study was designed as a prospective, randomized, experimental study using ex vivo porcine colorectal specimens. Thirty standardized and variable artificial perforations were closed in the hemoclip group (hemoclips) and twin grasper group (hemoclips with a novel tissue grasper). We counted the number of hemoclips used per case to assess the cost and efficacy of the procedure. RESULTS: In the hemoclip group (n = 15), among the 20-, 25-, and 30-mm defects, the mean number of clips (4.8 ± 0.8, 6.0 ± 1.6, and 8.4 ± 2.1, respectively, p = 0.011) and closure time (7.6 ± 0.5, 9.9 ± 3.3, and 13.9 ± 4.1 min, respectively, p = 0.020) differed significantly. In the twin grasper group (n = 15), among the 20-, 25-, and 30-mm defects, the mean number of clips (4.0 ± 1.0, 5.0 ± 0.7, and 5.4 ± 1.1, respectively, p = 0.101) and closure time (7.7 ± 0.6, 8.3 ± 1.9, and 9.1 ± 2.7 min, respectively, p = 0.506) did not differ significantly. In 30-mm defects, the mean number of hemoclips used per case and total closure time were significantly lower in the twin grasper group than the hemoclip group. CONCLUSIONS: The twin grasper-clips technique seems to reduce the use of hemoclips and to result in more effective and rapid closure than does the conventional technique in large perforations of the ex vivo porcine sigmoid colon.

Efficacy of midazolam- versus propofol-based sedations by non-anesthesiologists during therapeutic endoscopic retrograde cholangiopancreatography in patients aged over 80 years.

BACKGROUND AND AIM: As society ages, the need for endoscopic retrograde cholangiopancreatography (ERCP) is increasing. This prospective comparative study evaluated the safety and efficacy of midazolam- versus propofol-based sedations by non-anesthesiologists during therapeutic ERCP in patients over 80 years of age. METHODS: A total of 100 patients over 80 years of age who required therapeutic ERCP were enrolled and randomly received midazolam + fentanyl (MF group) or propofol + fentanyl (PF group) sedation. Endoscopic sedation was titrated to a moderate level and carried out by trained registered nurses. Main outcome measurements were sedation safety in terms of cardiopulmonary components and efficacy measured on a 10-point visual analogue scale (VAS). RESULTS: Regarding safety, hypoxia occurred in seven (14%) in the MF group and in eight patients (16%) in the PF group (P = 0.779). Increased O2 supply was more frequent in the PF group (32% vs 42%), albeit not significantly so. There were no differences in the frequency of hypotension, bradycardia or tachycardia between the two groups. Mean VAS score for overall satisfaction with sedation by patients, endoscopists, and nurses and the scores for pain during the procedures were not different between the two groups. There was no significant difference in the procedure outcomes or rate of ERCP-related complications. CONCLUSIONS: There were no significant differences of safety and efficacy between midazolam- and propofol-based sedation in patients over 80 years of age. Increased O2 supply was more frequent in the propofol group, but the prevalence of hypoxia did not differ significantly.

Third metal stent for revision of malignant hilar biliary strictures.

Background and study aim: Endoscopic stent-in-stent (SIS) placement of multiple metal stents is technically demanding. In the present study, we explored the technical feasibility and efficacy of endoscopic deployment of a third metal stent to create a triple SIS placement in patients with a bilateral SIS configuration for inoperable high grade malignant hilar biliary stricture (HBS) that had failed clinically. Methods: Eighteen patients with histologically proven inoperable HBS underwent deployment of an additional third metal stent as a revisionary method after early clinical failure following technically successful bilateral SIS placement using cross-wired metal stents. The main outcome measures were the technical and clinical success rates, and adverse events. Results: The overall technical and clinical success rates were 88.9 % (16/18) and 87.5 % (14/16), respectively. The early and late complications were cholangitis (n = 2) and cholecystitis (n = 1). Stent occlusion developed in 35.7 % (5/14) of patients in whom a third metal stent for revision of a bilateral SIS configuration was clinically successful. The median (range) times for stent patency and patient survival were 176 days (49 - 372) and 216 days (52 - 384), respectively. Conclusions: Endoscopic deployment of an additional third metal stent into a bilateral SIS configuration was technically feasible and effective in patients with inoperable high grade malignant HBS in whom bilateral SIS placement had failed clinically.

Decreased absorption of midazolam in the stomach due to low pH induced by co-administration of Banha-sasim-tang.

OBJECTIVES: Banha-sasim-tang (BST), which consists of seven different herbs, is one of the most popular herbal formulae for treating gastrointestinal disorders in Eastern Asia. The commonly used herbal medicine is often co-administered with other therapeutic drugs, which raises the possibility of herb-drug interactions and may modify the clinical safety profile of therapeutic drugs. METHODS: We investigated the potential herb-drug interactions between BST extract and midazolam (MDZ) in mice. The area under the plasma concentration-time curve (AUC) of MDZ and 1ʹ-hydroxymidazolam (1ʹ-OH-MDZ) was evaluated for both oral and intraperitoneal administration of MDZ, following oral administration of BST (0.5 and 1 g/kg). RESULTS: It was found that the AUC of MDZ and 1ʹ-OH-MDZ was lower in case of oral administration of MDZ. Administration of BST extract was not associated with hepatic cytochrome P450 activity. BST extract induced a strong reduction in pH and it has been reported that oral mucosal absorption of MDZ is lower at low pH. The decreased absorption rate of MDZ might be caused by the ingredients of BST and may not be related to other factors such as increased excretion of MDZ by P-glycoprotein. CONCLUSIONS: The altered pharmacokinetics of midazolam caused by co-administration with BST in vivo could be attributed to a decrease in pH and subsequent reduction of MDZ absorption rate.