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1.
Dig Dis Sci ; 68(10): 3963-3973, 2023 10.
Article in English | MEDLINE | ID: mdl-37658209

ABSTRACT

BACKGROUND AND AIMS: This randomized controlled trial (RCT) was designed to evaluate the short-term outcomes of underwater endoscopic mucosal resection (UEMR) and endoscopic submucosal dissection (ESD) of 21-30 mm colonic polyps. METHOD: We conducted a single-center RCT. Patients diagnosed with suspected colorectal intramucosal carcinoma (21-30 mm and adaptable for both UEMR and ESD) were randomly assigned to the UEMR and ESD groups at a 1:1 ratio. The primary endpoint was the R0 resection rate. We independently performed one-sample tests against the set threshold for each treatment. The significance level was set at p = 0.224. RESULT: Eleven polyps each in the UEMR and ESD groups, respectively, were analyzed. The R0 resection rate (%) was 36 (95% confidence interval 11-69) and 100 (72-100) for UEMR and ESD, respectively, with a significant difference between the two groups (p = 0.002). The p-value against the set threshold for UEMR was 0.743, whereas that for ESD was < 0.001 (one-sample binomial test). The en bloc resection rates (%) were 82 (48-97) and 100 (72-100) for UEMR and ESD, respectively; however, no significant difference was observed (p = 0.167). The mean treatment time (min) was significantly shorter in the UEMR group (8 ± 6) than in the ESD group (48 ± 29) (p = 0.001). CONCLUSION: ESD could achieve a high R0 resection rate, while the en bloc resection rate was comparable between the two treatment techniques with less burden on patients undergoing UEMR for 21-30-mm colorectal polyps. CLINICAL TRIAL REGISTRATION: The study was registered at the Japan Registry of Clinical Trial as jRCT1030210015 and jRCT1030210177.


Subject(s)
Colonic Polyps , Colorectal Neoplasms , Endoscopic Mucosal Resection , Humans , Colonic Polyps/surgery , Colorectal Neoplasms/surgery , Feasibility Studies , Japan
2.
Clin Gastroenterol Hepatol ; 21(10): 2551-2559.e2, 2023 09.
Article in English | MEDLINE | ID: mdl-36739935

ABSTRACT

BACKGROUND & AIMS: This study examined the additional value of magnifying chromoendoscopy (MCE) on magnifying narrow-band imaging endoscopy (M-NBI) in the optical diagnosis of colorectal polyps. METHODS: A multicenter prospective study was conducted at 9 facilities in Japan and Germany. Patients with colorectal polyps scheduled for resection were included. Optical diagnosis was performed by M-NBI first, followed by MCE. Both diagnoses were made in real time. MCE was performed on all type 2B lesions classified according to the Japan NBI Expert Team classification and other lesions at the discretion of endoscopists. The diagnostic accuracy and confidence of M-NBI and MCE for colorectal cancer (CRC) with deep invasion (≥T1b) were compared on the basis of histologic findings after resection. RESULTS: In total, 1173 lesions were included between February 2018 and December 2020, with 654 (5 hyperplastic polyp/sessile serrated lesion, 162 low-grade dysplasia, 403 high-grade dysplasia, 97 T1 CRCs, and 32 ≥T2 CRCs) examined using MCE after M-NBI. In the diagnostic accuracy for predicting CRC with deep invasion, sensitivity, specificity, positive predictive value, negative predictive value, and accuracy for M-NBI were 63.1%, 94.2%, 61.6%, 94.5%, and 90.2%, respectively, and for MCE they were 77.4%, 93.2%, 62.5%, 96.5%, and 91.1%, respectively. The sensitivity was significantly higher in MCE (P < .001). However, these additional values were limited to lesions with low confidence in M-NBI or the ones diagnosed as ≥T1b CRC by M-NBI. CONCLUSIONS: In this multicenter prospective study, we demonstrated the additional value of MCE on M-NBI. We suggest that additional MCE be recommended for lesions with low confidence or the ones diagnosed as ≥T1b CRC. Trials registry number: UMIN000031129.


Subject(s)
Colonic Polyps , Colorectal Neoplasms , Humans , Colonic Polyps/diagnostic imaging , Colonic Polyps/pathology , Colonoscopy/methods , Prospective Studies , Colorectal Neoplasms/pathology , Sensitivity and Specificity , Narrow Band Imaging/methods
3.
Sci Rep ; 12(1): 10381, 2022 06 20.
Article in English | MEDLINE | ID: mdl-35725752

ABSTRACT

This pilot study aimed to investigate the utility of texture and color enhancement imaging (TXI) with magnified endoscopy (ME) for the preoperative diagnosis of superficial nonampullary duodenal epithelial tumors (SNADETs). We prospectively evaluated 12 SNADETs. The visibility for ME-TXI, ME with indigo carmine (ICME)-white-light imaging (WLI), ICME-TXI compared to ME-NBI (narrow-band imaging) was scored (+ 2 to - 2 ME-NBI was set as score 0) by 3 experts. Scores + 2 and + 1 were defined as improved visibility. The intra-observer and interobserver agreement for improved visibility of surface structure (SS) was evaluated. Sensitivity, specificity, and positive predictive value (PPV) for Vienna Classification (VCL) C4/5 associated with the preoperative diagnosis of ICME-TXI were analyzed. The SS visibility score of ICME-TXI was significantly higher than that of ME-NBI, ME-TXI, and ICME-WLI (P < 0.001 respectively). The kappa coefficients of reliability for intra-observer and interobserver agreement for the SS visibility improvement with ICME-TXI were 0.96, 1.00, 1.00 and 0.70, 0.96, 0.96 respectively. All endoscopists preferred ICME-TXI for visualizing SS mostly for all lesions. The sensitivity, specificity, and PPV (%) of ICME-TXI for VCL C4/5 were 80, 66.7, and 63.2, respectively. ICME-TXI facilitates the visibility of the SS of SNADETs and may contribute to their preoperative diagnosis.


Subject(s)
Duodenal Neoplasms , Indigo Carmine , Endoscopy, Gastrointestinal , Humans , Narrow Band Imaging/methods , Pilot Projects , Reproducibility of Results
4.
Gastrointest Endosc ; 95(5): 939-947, 2022 05.
Article in English | MEDLINE | ID: mdl-35065947

ABSTRACT

BACKGROUND AND AIMS: The appropriate selection of endoscopic resection for relatively small superficial nonampullary duodenal adenomas (SNADAs) considering recurrence is not completely clarified. Therefore, this study investigated endoscopic resection utility (EMR, underwater EMR [UEMR], and cap-assisted EMR [EMRC]) for SNADAs from the viewpoint of recurrence and short-term outcomes. METHODS: We retrospectively analyzed patients with sporadic SNADAs who underwent EMR, UEMR, and EMRC at Chiba University Hospital between May 2004 and March 2020 and were observed for ≥12 months after endoscopic resection (EMR, 34 patients, 36 lesions; UEMR, 54 patients, 55 lesions; and EMRC, 45 patients, 48 lesions). Outcomes were evaluated using weighted logistic regression analysis. The logistic regression analysis was weighted using propensity scores. RESULTS: EMRC showed significantly higher en-bloc and R0 resection rates than EMR. All techniques were equally safe. Only 1 case each of intraoperative perforation and postoperative perforation (in 2 different patients) occurred, which were associated with EMRC. UEMR resulted in higher R0 resection and lower postbleeding rates than EMR. Moreover, patients who underwent UEMR showed no perforation. Median observation period per lesion after endoscopic resection was 84 months (range, 16-199) for patients who underwent EMR, 25 months (range, 12-60) for patients who underwent UEMR, and 63 months (range, 12-180) for patients who underwent EMRC. No significant difference was observed between EMR versus UEMR and between EMR versus EMRC in terms of recurrence (odds ratio, .20 [95% confidence interval, .01-2.86; P = .24] and .78 [95% confidence interval, .09-6.84; P = .82], respectively). CONCLUSIONS: Recurrence risk was not different for EMR, UEMR, and EMRC. Therefore, UEMR, a simple and safe procedure, could be the first choice for relatively small SNADAs. With larger prospective studies, UEMR data may turn out to be more robust, corroborating it as the endoscopic modality of choice for certain SNADAs.


Subject(s)
Adenoma , Duodenal Neoplasms , Endoscopic Mucosal Resection , Adenoma/pathology , Duodenal Neoplasms/pathology , Endoscopic Mucosal Resection/methods , Humans , Intestinal Mucosa/pathology , Prospective Studies , Retrospective Studies , Treatment Outcome
5.
J Gastroenterol Hepatol ; 37(1): 75-80, 2022 Jan.
Article in English | MEDLINE | ID: mdl-34409657

ABSTRACT

BACKGROUND AND AIM: The effectiveness of cold snare polypectomy (CSP) for superficial non-ampullary duodenal epithelial tumors (SNADETs) regarding long-term outcomes is not fully clarified. This study aimed to investigate long-term outcomes of CSP for SNADETs. METHODS: Patients diagnosed with sporadic SNADETs and treated with CSP at Chiba University Hospital between March 2015 and May 2018 were retrospectively analyzed. Long-term outcomes, short-term outcomes, and adverse events were investigated. RESULTS: In total, 35 patients with 46 lesions were included. The en-bloc resection rate was 97.8%. Thirty-seven lesions (80.4%) were diagnosed as adenomatous. The R0 resection rate for adenomatous lesions was 70.3%. Follow-up investigations more than 12 months after CSP were completed for 35 adenomatous lesions (94.6%). The median observation period after CSP was 48 months. One patient whose observation period was only 3 months died from chronic heart failure with cardiac sarcoidosis 6 months after CSP. No patient died from SNADETs. The relapse-free survival rate at 12 months after CSP was 97.1%. One recurrence (2.7%) was observed 12 months after CSP. We removed the recurrence lesion with CSP and cold forceps polypectomy. No new recurrence occurred within the observation period. No perforation or post-operative bleeding occurred for CSP. CONCLUSIONS: Cold snare polypectomy for diminutive and small SNADETs is a safe and useful procedure with a high en-bloc resection rate and long-term local control capability.


Subject(s)
Adenocarcinoma , Colectomy , Colonic Polyps , Duodenal Neoplasms , Adenocarcinoma/surgery , Colectomy/adverse effects , Colectomy/methods , Colonic Polyps/surgery , Duodenal Neoplasms/surgery , Humans , Retrospective Studies , Treatment Outcome
6.
Gastrointest Endosc ; 95(1): 140-148, 2022 Jan.
Article in English | MEDLINE | ID: mdl-34284025

ABSTRACT

BACKGROUND AND AIMS: The application of underwater EMR (UEMR) for nonpolypoid superficial nonampullary duodenal epithelial tumors (SNADETs) has not been comprehensively assessed. Therefore, the current study aimed to validate the efficacy of UEMR versus conventional EMR and cap-assisted EMR (EMRC) for SNADETs measuring ≤20 mm. METHODS: We retrospectively analyzed patients with sporadic nonpolypoid SNADETs measuring ≤20 mm undergoing EMR, EMRC, or UEMR at Chiba University Hospital between May 2004 and October 2020 (EMR, 21 patients and 23 SNADETs; UEMR, 60 patients and 61 SNADETs; EMRC, 45 patients and 48 SNADETs). A weighted logistic regression analysis was performed to analyze outcomes. Univariate and multivariate logistic regression models were used to identify the predictors of RX/1 and piecemeal resection. The recurrence rate of lesions observed ≥12 months after resection was assessed. RESULTS: Both UEMR and EMRC had a significantly higher R0 resection rate than EMR. UEMR had significantly lower multiple resection and postbleeding rates than EMR. Only 1 patient (2.1%) who underwent EMRC experienced intraoperative and postoperative perforation. EMR was involved in RX/1 and piecemeal resection. The recurrence rates of EMR, UEMR, and EMRC were 4.3%, 2.0%, and 6.3%, respectively. CONCLUSIONS: UEMR had significantly higher R0 resection and lower postbleeding rates than EMR. Moreover, it was safer than EMRC and was associated with a lower incidence of recurrences. The significant results of the retrospective analysis suggest a randomized controlled study with adequate numbers needs to be conducted to confirm the superior efficacy of UEMR before it is recommended for primary treatment option for SNADETs measuring ≤20 mm.


Subject(s)
Duodenal Neoplasms , Endoscopic Mucosal Resection , Neoplasms, Glandular and Epithelial , Duodenal Neoplasms/surgery , Humans , Intestinal Mucosa , Retrospective Studies
7.
J Neurogastroenterol Motil ; 27(4): 545-554, 2021 Oct 30.
Article in English | MEDLINE | ID: mdl-34642275

ABSTRACT

BACKGROUND/AIMS: Esophageal motility disorders (EMDs) contribute to the pathophysiology of gastroesophageal reflux disease. However, the causes of EMDs and their impact on gastroesophageal reflux disease-associated symptoms remain unknown. This study aims to elucidate clinical features associated with various types of EMDs in patients with heartburn symptoms. METHODS: Of the 511 patients who underwent high-resolution manometry, 394 who were evaluated for heartburn symptoms were examined. Patients subjected to high-resolution manometry were classified into 4 groups: outflow obstruction group, hypermotility group, hypomotility group, and normal motility group. Symptoms were evaluated using 3 questionnaires. Patient characteristics and symptoms for each EMD type were compared with those of the normal motility group. RESULTS: Of the 394 patients, 193 (48.9%) were diagnosed with EMDs, including 71 with outflow obstruction, 15 with hypermotility, and 107 with hypomotility. The mean dysphagia score was significantly higher in each of the 3 EMD groups compared with those with normal motility. The mean acid reflux and dyspepsia scores were significantly lower in the outflow obstruction group (P < 0.05). The mean body mass index and median Brinkman index were significantly higher in the hypermotility group (P = 0.001 and P = 0.018, respectively), whereas the mean diarrhea and constipation scores were significantly lower in the hypomotility group (P < 0.05). CONCLUSIONS: The results of our study indicate that different EMDs have distinct characteristics. Cigarette smoking and high body mass index were associated with esophageal hypermotility. Assessment of the dysphagia symptom scores may help identify patients with EMDs.

8.
Cancer Med ; 10(11): 3545-3555, 2021 06.
Article in English | MEDLINE | ID: mdl-33934524

ABSTRACT

Somatic mutations including the background mucosa in patients with Lugol-voiding lesions (LVLs) are still not well known. The aim of this study was to evaluate the somatic mutations of the background mucosa in patients with LVLs (Squamous cell carcinoma (SCC), intraepithelial neoplasia (IN), and hyperplasia). Twenty-five patients with LVLs (9 with SCC, 6 with IN, and 10 with hyperplasia) were included. A targeted sequence was performed for LVLs and background mucosa using an esophageal cancer panel. Each mutation was checked whether it was oncogenic or not concerning OncoKB. In LVLs, TP53 was the most dominant mutation (80%). Furthermore, 72% of TP53 mutations was putative drivers. In background mucosa, NOTCH1 was the most dominant mutation (88%) and TP53 was the second most dominant mutation (48%). Furthermore, 73% of TP53 mutations and 8% of NOTCH1 mutations were putative drivers. Putative driver mutations of TP53 had significantly higher allele frequency (AF) in SCC than in IN and hyperplasia. Conversely, putative driver mutations of NOTCH1 did not have a significant accumulation of AF in the progression of carcinogenesis. Furthermore, in SCC, AF of TP53 mutations was significantly higher in LVLs than in background mucosa, but not in IN and hyperplasia. Regarding NOTCH1, a significant difference was not observed between LVLs and background mucosa in each group. The background mucosa in patients with LVLs already had putative driver mutations such as TP53 and NOTCH1. Of these two genes, TP53 mutation could be the main target gene of carcinogenesis in esophageal SCC. Clinical Trials registry: UMIN000034247.


Subject(s)
Carcinoma in Situ/genetics , Esophageal Mucosa , Esophageal Neoplasms/genetics , Esophageal Squamous Cell Carcinoma/genetics , Genes, p53 , Mutation , Receptor, Notch1/genetics , Aged , Alcohol Drinking , Alleles , Carcinogenesis/genetics , Carcinoma in Situ/pathology , Case-Control Studies , DNA Mutational Analysis , Disease Progression , Esophageal Mucosa/pathology , Esophageal Neoplasms/pathology , Esophageal Squamous Cell Carcinoma/pathology , Female , Gene Frequency , Humans , Hyperplasia/genetics , Hyperplasia/pathology , Iodides , Japan , Male , Smoking , Statistics, Nonparametric
9.
Dig Dis Sci ; 66(8): 2674-2681, 2021 08.
Article in English | MEDLINE | ID: mdl-32840705

ABSTRACT

BACKGROUND/AIM: Barrett's esophagus (BE) is a precursor of esophageal adenocarcinoma (EAC). Therefore, an accurate diagnosis of BE is important for the subsequent follow-up and early detection of EAC. However, the definitions of BE have not been standardized worldwide; columnar-lined epithelium (CLE) without intestinal metaplasia (IM) and/or < 1 cm is not diagnosed as BE in most countries. This study aimed to clarify the malignant potential of CLE without IM and/or < 1 cm genetically. METHOD: A total of 96 consecutive patients (including nine patients with EAC) who had CLE were examined. Biopsies for CLE were conducted, and patients were divided into those with IM and > 1 cm (Group A) and those without IM and/or < 1 cm (Group B). Malignant potential was assessed using immunochemical staining for p53. Moreover, causative genes were examined using next-generation sequencing (NGS) on ten patients without Helicobacter pylori infection and without atrophic gastritis. RESULT: Of the 96 patients, 66 were in Group B. The proportion of carcinoma/dysplasia in Group A was significantly higher than that in Group B (26.7% in Group A and 1.5% in Group B; p < 0.01). However, one EAC patient was found in Group B. In the immunostaining study for non-EAC patients, an abnormal expression of p53 was not observed in Group A, whereas p53 loss was observed in three patients (4.6%) in Group B. In the NGS study, a TP53 mutation was found in Group B. CONCLUSION: CLE without IM and/or < 1 cm has malignant potential. This result suggests that patients with CLE as well as BE need follow-up.


Subject(s)
Barrett Esophagus/complications , Barrett Esophagus/pathology , Epithelium/pathology , Esophageal Neoplasms/complications , Asian People , Carcinoma/complications , Carcinoma/pathology , Humans , Japan , Retrospective Studies , Risk Factors , Tumor Suppressor Protein p53
10.
Sci Rep ; 10(1): 20667, 2020 11 26.
Article in English | MEDLINE | ID: mdl-33244140

ABSTRACT

The current study aimed to evaluate the efficacy of linked color imaging (LCI) in improving the visibility of superficial non-ampullary duodenal epithelial tumors (SNADETs). We prospectively evaluated 44 consecutive patients diagnosed with SNADETs. Three trainees and three experts assessed the visibility scores of white light imaging (WLI), LCI, and blue laser imaging-bright (BLI-b) for SNADETs, which ranged from 1 (not detectable without repeated cautious examination) to 4 (excellent visibility). In addition, the L* a* b* color values and color differences (ΔE*) were evaluated using the CIELAB color space system. For SNADETs, the visibility scores of LCI (3.53 ± 0.59) were significantly higher than those of WLI and BLI-b (2.66 ± 0.79 and 3.41 ± 0.64, respectively). The color differences (ΔE*) between SNADETs and the adjacent normal duodenal mucosa in LCI mode (19.09 ± 8.33) were significantly higher than those in WLI and BLI-b modes (8.67 ± 4.81 and 12.92 ± 7.95, respectively). In addition, the visibility score of SNADETs and the color differences in LCI mode were significantly higher than those in WLI and BLI-b modes regardless of the presence of milk white mucosa (MWM). LCI has potential benefits, and it is considered a promising clinical modality that can increase the visibility of SNADETs regardless of the presence of MWM.This study was registered at the University Hospital Medical Information Network (UMIN000028840).


Subject(s)
Duodenal Neoplasms/diagnosis , Neoplasms, Glandular and Epithelial/diagnosis , Aged , Colonoscopy/methods , Color , Duodenal Neoplasms/pathology , Duodenum/pathology , Female , Humans , Image Enhancement/methods , Intestinal Mucosa/pathology , Light , Male , Neoplasms, Glandular and Epithelial/pathology , Prospective Studies
11.
Gastroenterol Res Pract ; 2020: 9604345, 2020.
Article in English | MEDLINE | ID: mdl-33061962

ABSTRACT

BACKGROUND: The present study aimed to evaluate the efficacy of linked color imaging (LCI) in diagnosing Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC). METHODS: A total of 112 and 12 consecutive patients with BE and EAC were analyzed. The visibility scores of BE and EAC ranging from 4 (excellent visibility) to 0 (not detectable) were evaluated by three trainees and three experts using white light imaging (WLI), LCI mode, and blue laser imaging bright (BLI-b) mode. In addition, L∗a∗b∗ color values and color differences (ΔE∗) were evaluated using the CIELAB color space system. RESULTS: The visibility score of the BE in LCI mode (2.94 ± 1.32) was significantly higher than those in WLI (2.46 ± 1.48) and BLI-b mode (2.35 ± 1.46) (p < 0.01). The color difference (ΔE∗) from the adjacent gastric mucosa in LCI mode (17.11 ± 8.53) was significantly higher than those in other modes (12.52 ± 9.37 in WLI and 11.96 ± 6.59 in BLI-b mode, p < 0.01). The visibility scores of EAC in LCI mode (2.56 ± 1.47) and BLI-b mode (2.51 ± 1.28) were significantly higher than that in WLI (1.64 ± 1.46) (p < 0.01). The color difference (ΔE∗) from the adjacent normal Barrett's mucosa in LCI mode (19.96 ± 7.97) was significantly higher than that in WLI (12.95 ± 11.86) (p = 0.03). CONCLUSION: The present findings suggest that LCI increases the visibility of BE and EAC and contributes to the improvement of the detection of these lesions.

12.
Dis Esophagus ; 33(9)2020 Sep 04.
Article in English | MEDLINE | ID: mdl-32409817

ABSTRACT

Ineffective esophageal motility (IEM) is the most common manometric abnormality in gastroesophageal reflux disease (GERD). However, the impact of IEM on esophageal chemical clearance has not been fully investigated. This study aimed to determine the impact of IEM on esophageal chemical clearance in patients with GERD. A total of 369 patients with GERD symptoms who underwent upper endoscopy and high-resolution manometry (HRM) test were retrospectively analyzed. The relationship between IEM and erosive esophagitis was examined. In addition, the impact of IEM on chemical clearance was examined in patients who underwent an additional combined multichannel intraluminal impedance-pH (MII-pH) test. Esophageal chemical clearance capability was evaluated via postreflux swallow-induced peristaltic wave (PSPW) index and acid clearance time (ACT). Of 369 patients, 181 (49.1%) had esophageal motility disorders, of which 78 (21.1%) had IEM. The proportion of IEM patients in those with erosive esophagitis and those without were 16.2% and 21.7%, respectively, and no significant difference was observed (P = 0.53). After excluding patients other than those with IEM and normal esophageal motility, 64 subsequently underwent MII-pH test. The median values of the PSPW index in the IEM and normal esophageal motility group were 11.1% (4.2%-20.0%) and 17.1% (9.8%-30.6%), respectively. The PSPW index was significantly lower in the IEM group than in the normal esophageal motility group (P < 0.05). The median ACT values in the IEM group and normal esophageal motility group were 125.5 (54.0-183.5) seconds and 60.0 (27.2-105.7) seconds, respectively. The ACT was significantly longer in the IEM group than in the normal esophageal motility group (P < 0.05). In conclusion, IEM was found to be associated with chemical clearance dysfunction as measured against the PSPW index and ACT. As this condition could be a risk factor for GERD, future treatments should be developed with a focus on chemical clearance.


Subject(s)
Esophageal Motility Disorders , Gastroesophageal Reflux , Esophageal Motility Disorders/etiology , Esophageal pH Monitoring , Humans , Manometry , Retrospective Studies
13.
Drug Res (Stuttg) ; 70(5): 199-205, 2020 May.
Article in English | MEDLINE | ID: mdl-32193878

ABSTRACT

In Japan, tuberculosis has been recognized as one of the major infections requiring urgent measures because of its high morbidity rate even now especially in elderly people suffering from tuberculosis during the past epidemic and its reactivation. Hence, many Japanese clinicians have made efforts to suppress the onset of tuberculosis and treat it effectively. The objectives of this study are to (1) identify covariate(s) that may explain the variation of rifampicin, which is the key antitubercular agent, under the steady-state by evaluating its population pharmacokinetics and (2) to propose an appropriate dosing method of rifampicin to Japanese patients. For this purpose, serum concentration-time data were obtained from 138 patients receiving rifampicin (300-450 mg) and isoniazid (300-400 mg) every day over 14 days, and analyzed using nonlinear mixed effects model. Thereby, population pharmacokinetic parameters were estimated followed by elucidating relations between the parameters and statistical factors. The analysis adopted one-compartment model including Lag-time by assuming that the absorption process is 0+1st order. The analyses demonstrate that meal affected the bioavailability, primary absorption rate constant, and zero order absorption time in the constructed model. A body weight calculated from the power model was selected as the covariate by the Stepwise Covariate Model method and found to highly affect the clearance in the range from -31.6% to 47.4%. We conclude that the dose in Japanese tuberculous patients can be well estimated by the power model formula and should be taken into consideration when rifampicin is administered.


Subject(s)
Antitubercular Agents/pharmacokinetics , Biological Variation, Population , Models, Biological , Rifampin/pharmacokinetics , Tuberculosis, Pulmonary/drug therapy , Adult , Aged , Aged, 80 and over , Antitubercular Agents/administration & dosage , Antitubercular Agents/chemistry , Biological Availability , Dose-Response Relationship, Drug , Drug Administration Schedule , Female , Food-Drug Interactions , Gastrointestinal Absorption , Humans , Japan , Male , Middle Aged , Retrospective Studies , Rifampin/administration & dosage , Rifampin/chemistry , Solubility , Tuberculosis, Pulmonary/blood , Young Adult
14.
Scand J Gastroenterol ; 55(2): 209-215, 2020 Feb.
Article in English | MEDLINE | ID: mdl-32008404

ABSTRACT

Objective: Long-term administration of proton pump inhibitors (PPIs) after eradication of Helicobacter pylori infection has been reported to increase the risk for development of gastric cancer (GC). We investigated whether long-term administration of PPI affects ectopic and metachronous recurrence of GC after endoscopic treatment.Methods: Participants were 687 patients who underwent endoscopic treatment for GC from January 2005 to March 2018. Questionnaire surveys and medical record reviews of medications, including PPIs, H2 receptor antagonists and low-dose aspirin (LDA) were conducted for all patients. The influence of PPI in ectopic and metachronous recurrence of GC was evaluated with Cox's proportional hazard analysis.Results: Patients who did not respond to the questionnaire and those who underwent additional treatment after endoscopic treatment were excluded from analyses; 418 patients were included. During an average observation period of 1608 days (range, 375-4993 days), 136 patients (32.5%) took PPIs for more than 1 year and 94 took PPIs for more than 3 years; of those, 40 had ectopic and metachronous recurrences. Cox's proportional hazards analysis revealed that long-term use of PPIs (for both 1 year and 3 years) was not a risk factor for recurrence. In addition, age, severity of gastric atrophy, long-term use of LDA, current infection with H. pylori, and cure achieved with the first endoscopic treatment were also not risk factors for recurrence.Conclusions: Long-term use of PPIs does not affect ectopic and metachronous recurrence of GC after endoscopic treatment.


Subject(s)
Helicobacter Infections/complications , Neoplasms, Second Primary/epidemiology , Proton Pump Inhibitors/therapeutic use , Stomach Neoplasms/epidemiology , Stomach Neoplasms/surgery , Aged , Aged, 80 and over , Aspirin/therapeutic use , Female , Gastroscopy/adverse effects , Helicobacter Infections/drug therapy , Histamine H2 Antagonists/therapeutic use , Humans , Incidence , Japan/epidemiology , Male , Middle Aged , Multivariate Analysis , Neoplasms, Second Primary/etiology , Neoplasms, Second Primary/pathology , Proportional Hazards Models , Retrospective Studies , Risk Factors , Stomach Neoplasms/pathology
15.
Esophagus ; 17(3): 339-347, 2020 07.
Article in English | MEDLINE | ID: mdl-31982992

ABSTRACT

BACKGROUND: Salivary pepsin measurement has been reported to be useful for diagnosing gastroesophageal reflux disease (GERD). This study aimed to clarify the usefulness of salivary pepsin measurement in patients with proton pump inhibitor (PPI)-refractory GERD symptoms without erosive esophagitis. METHODS: One hundred and two patients were included. Over seven days after terminating PPI treatment, all patients underwent a 24-h pH-impedance test and salivary pepsin measurement. In patients whose main symptoms included laryngopharyngeal symptoms, a hypopharyngeal multichannel intraluminal impedance (HMII) test was performed, whereas in other patients, a conventional combined multichannel intraluminal impedance-pH (MII-pH) test was performed. In the HMII tests, patients were divided into abnormal proximal exposure (APE) and non-APE groups. Salivary pepsin concentrations were compared according to acid exposure time (AET) values and were also compared between the APE and non-APE groups. RESULTS: The median salivary pepsin concentration in patients with AET > 6% was significantly higher than that in patients with AET ≤ 6% (345.0 [170.0-469.3] ng/mL vs. 120.0 [97.0-290.1] ng/mL, p < 0.01). The sensitivity, specificity, positive predictive value, and negative predictive value of a positive test (> 109 ng/mL) to diagnose patients with AET > 6% were 75.0%, 51.3%, 32.1%, and 86.9%, respectively. There was no significant difference between concentrations in the APE group and concentrations in the non-APE group. CONCLUSIONS: In patients with PPI-refractory nonerosive reflux disease, salivary pepsin measurement may help diagnose patients who have conclusive evidence of reflux, whereas it is not adequate for identifying patients with APE.


Subject(s)
Gastroesophageal Reflux/metabolism , Pepsin A/analysis , Proton Pump Inhibitors/therapeutic use , Saliva/metabolism , Adult , Aged , Drug Resistance , Electric Impedance , Esophageal pH Monitoring/methods , Female , Gastroesophageal Reflux/diagnosis , Gastroesophageal Reflux/drug therapy , Humans , Hypopharynx/pathology , Laryngopharyngeal Reflux/diagnosis , Laryngopharyngeal Reflux/epidemiology , Male , Middle Aged , Predictive Value of Tests , Prospective Studies , Sensitivity and Specificity
16.
Can J Gastroenterol Hepatol ; 2019: 7145182, 2019.
Article in English | MEDLINE | ID: mdl-31583220

ABSTRACT

Introduction: Endoscopic submucosal dissection (ESD) for early gastric cancer (EGC) is well accepted. However, its adaptation for elderly patients is unclear. This study aimed to investigate the prognosis and long-term outcomes of ESD for EGC in elderly patients aged ≥80 years by comparing their findings to the findings of patients aged <80 years. Materials and Methods: The study included 533 patients (632 lesions). The patients were divided into an elderly group (age, ≥80 years; 108 patients; 128 lesions; mean age, 83.4 ± 2.7 years) and a nonelderly group (age, <80 years; 425 patients; 504 lesions; mean age, 69.6 ± 7.9 years). We compared patient and lesion characteristics, overall survival (OS), and disease-specific survival (DSS) between the 2 groups retrospectively. Multivariate analysis was performed to clarify the risk factors of death after ESD. Results: The rate of curative resection and adverse events was not significantly different between the groups. The mean survival time periods with regard to OS/DSS in the elderly and nonelderly groups were 75.8 ± 5.9 and 122.8 ± 2.6 months (P < 0.05)/120.0 ± 3.0 and 136.4 ± 0.6 months (not significant), respectively. In the elderly group, eGFR <30 ml/min/1.73 m2 was an independent risk factor of death (hazard ratio = 5.32; 95% confidence interval = 1.39-20.5; P=0.015). Conclusion: ESD for EGC can be performed safely and can achieve high curability with good prognosis in elderly patients aged ≥80 years. After ESD, close attention should be paid to elderly patients with severe chronic kidney disease.


Subject(s)
Adenocarcinoma/mortality , Adenocarcinoma/surgery , Endoscopic Mucosal Resection , Renal Insufficiency, Chronic/complications , Stomach Neoplasms/mortality , Stomach Neoplasms/surgery , Adenocarcinoma/complications , Age Factors , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Renal Insufficiency, Chronic/mortality , Retrospective Studies , Risk Factors , Stomach Neoplasms/complications , Survival Rate , Treatment Outcome
17.
Dig Endosc ; 31(6): 662-671, 2019 Nov.
Article in English | MEDLINE | ID: mdl-31038769

ABSTRACT

BACKGROUND AND AIM: Cold snare polypectomy (CSP) is a safe treatment for colorectal adenomas. However, the R0 resection rate is not sufficiently high because of inadequate resection of muscularis mucosa. We hypothesized that CSP in an underwater environment could improve this procedure by helping to safely achieve resection containing the muscularis mucosa. We have named this procedure underwater cold snare polypectomy (UCSP). We aimed to investigate the efficacy and safety of UCSP for colorectal adenomas. METHODS: Between May 2017 and April 2018, patients diagnosed with colorectal adenomas <9 mm underwent UCSP. After follow-up colonoscopy 3 weeks later, the patients post-UCSP scars were biopsied. Outcomes were compared with those of a historical control group who underwent conventional CSP in our previous study using propensity score-matching methods. RESULTS: Overall, 224 lesions in 65 patients were prospectively resected by UCSP. Pathologically, 209 lesions were adenomas (4.5 ± 1.5 mm) including one intramucosal carcinoma. Only one pathological residual adenoma was identified, but there was no significant difference in the residual rate between the UCSP and CSP groups (both 1.0%). No complications were observed. R0 resection rate and rate of area containing the muscularis mucosa in the UCSP group were significantly higher than those in the CSP group (80.2% vs 32.7%, P < 0.001; 50.0% vs 35.3%, P = 0.015). CONCLUSION: Underwater cold snare polypectomy for diminutive and small colorectal adenomas was safe and effective from the perspective of pathological complete resection, which is likely facilitated by achieving an adequate depth of resection.


Subject(s)
Adenoma/surgery , Colonoscopy/methods , Colorectal Neoplasms/surgery , Digestive System Surgical Procedures/methods , Microsurgery/methods , Adenoma/diagnosis , Aged , Aged, 80 and over , Biopsy , Cold Temperature , Colorectal Neoplasms/diagnosis , Female , Follow-Up Studies , Humans , Male , Middle Aged , Retrospective Studies , Treatment Outcome
18.
Clin J Gastroenterol ; 12(4): 330-335, 2019 Aug.
Article in English | MEDLINE | ID: mdl-30903514

ABSTRACT

Epstein-Barr virus (EBV)-positive mucocutaneous ulcer is a B-cell lymphoproliferative disorder occurring in elderly or iatrogenic immunocompromised patients. We report a 27-year-old male patient with Crohn's disease (CD) who developed immunomodulator-associated lymphoproliferative disorder. The patient was diagnosed with CD at the age of 17 and was treated with maintenance therapy including high-dose infliximab and azathioprine. When he was admitted to our hospital with a diagnosis of intestinal obstruction, his abdominal computed tomography findings showed not only colonic wall thickening and narrowing of the descending colon but also multiple liver tumor lesions. His ileus symptom improved with conservative therapy, and a pathological evaluation of the tissue biopsy specimens from the descending colon and liver lesions indicated a morphological diagnosis of EBV-positive diffuse large B-cell lymphoma. This was a case of iatrogenic immunodeficiency-associated lymphoproliferative disorder due to an immunomodulator. The treatment was initiated with chemotherapy, but he died of disease progression 10 months after the diagnosis of lymphoma. Although cases of lymphoproliferative disorder due to treatment modalities used for CD are rare in Japan, an increase in the risk of lymphoproliferative diseases should be considered in patients with CD treated with immunomodulatory agents.


Subject(s)
Crohn Disease/drug therapy , Epstein-Barr Virus Infections/complications , Immunosuppressive Agents/adverse effects , Lymphoma, Large B-Cell, Diffuse/virology , Adult , Colonic Neoplasms/diagnostic imaging , Colonic Neoplasms/immunology , Colonic Neoplasms/virology , Colonoscopy , Crohn Disease/immunology , Epstein-Barr Virus Infections/immunology , Fatal Outcome , Humans , Immunocompromised Host , Immunosuppressive Agents/therapeutic use , Liver Neoplasms/diagnostic imaging , Liver Neoplasms/immunology , Liver Neoplasms/virology , Lymphoma, Large B-Cell, Diffuse/diagnostic imaging , Lymphoma, Large B-Cell, Diffuse/immunology , Male , Tomography, X-Ray Computed , Ulcer/immunology , Ulcer/virology
19.
Digestion ; 100(1): 37-44, 2019.
Article in English | MEDLINE | ID: mdl-30636251

ABSTRACT

AIMS: We evaluated the long-term prognosis of patients with obscure gastrointestinal bleeding (OGIB) who underwent capsule endoscopy (CE). METHODS: In our hospital, 429 patients underwent CE between November 2007 and March 2012. Among them, 259 patients underwent CE as the first examination for OGIB and were then followed at 77 clinics and hospitals. The clinical characteristics were investigated, including age, gender, overt/occult bleeding, the use of antithrombotic drugs and NSAIDs, complications (liver cirrhosis and hemodialysis), and CE. We asked the medical institutions for their survival data as of August 2017 (> 5 years after CE). RESULTS: The prognoses of 240 patients (92.6%) were analyzed. The average follow-up period was 55.7 (1-115) months. During the follow-up period, 57 patients (23.8%) died and the survival rates were 90.5% at 1 year, 81.7% at 3 years, and 74.7% at 5 years. Age 65 years or older and liver cirrhosis were predictive factors for a poor prognosis. Rebleeding occurred in 42 patients (17.9%) and small bowel cancer and gastrointestinal stromal tumor were found at 12 and 21 months after CE, respectively. CONCLUSIONS: Patients with OGIB showed a poor prognosis, especially those who were elderly or who had liver cirrhosis.


Subject(s)
Gastrointestinal Hemorrhage/mortality , Gastrointestinal Neoplasms/complications , Liver Cirrhosis/complications , Age Factors , Aged , Aged, 80 and over , Capsule Endoscopy , Female , Follow-Up Studies , Gastrointestinal Hemorrhage/diagnostic imaging , Gastrointestinal Hemorrhage/etiology , Gastrointestinal Neoplasms/mortality , Humans , Liver Cirrhosis/mortality , Male , Middle Aged , Prognosis , Recurrence , Retrospective Studies , Risk Factors , Sex Factors , Survival Rate
20.
J Gastroenterol Hepatol ; 34(5): 870-879, 2019 May.
Article in English | MEDLINE | ID: mdl-30225931

ABSTRACT

BACKGROUND AND AIM: Venous thromboembolism (VTE) is a common complication of inflammatory bowel disease (IBD). The aim of the present study was to identify predictors of VTE in hospitalized patients with IBD. METHODS: Patients with IBD who were hospitalized from February 2015 to March 2016 at the Chiba University Hospital were included. VTE was detected using enhanced computed tomography, and VTE onset within 2 months after admission was assessed. Predictors of VTE onset were investigated with clinical factors during hospitalization. Availability of the Caprini risk assessment model and Padua prediction score at the time of admission was also assessed. RESULTS: Seventy-two patients with IBD were hospitalized, and central venous catheters were placed in 43 of the 72 patients. During the observation period, VTE occurred in six patients (8.3%); however, none died as a result of the condition. Cox proportional hazards regression analysis identified D-dimer values on admission as a risk factor that was highly associated with VTE onset (hazard ratio = 1.590; 95% confidence interval, 1.132-2.233; P = 0.007) and significantly predicted the occurrence of VTE using the receiver operating characteristic curve (P = 0.005, area under the curve = 0.893). However, Caprini risk assessment model and Padua prediction scores were not useful tools for predicting VTE onset in patients with IBD. CONCLUSION: In hospitalized patients with IBD, D-dimer values were highly associated with VTE onset. Therefore, measurement of D-dimer values on admission is critical for the management of thromboembolic complications in patients with IBD.


Subject(s)
Inflammatory Bowel Diseases/complications , Venous Thromboembolism/diagnosis , Venous Thromboembolism/etiology , Adult , Biomarkers/blood , Female , Fibrin Fibrinogen Degradation Products/metabolism , Forecasting , Hospitalization , Humans , Male , Middle Aged , ROC Curve , Risk Assessment/methods , Risk Factors , Tomography, X-Ray Computed , Venous Thromboembolism/epidemiology , Young Adult
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