Development and Validation of a Simple and Multifaceted Instrument, Chronic Constipation-Therapeutic Efficacy and Satisfaction Test, for the Clinical Evaluation of Patients with Chronic Constipation.

INTRODUCTION: This study evaluated the psychometric properties of the newly developed chronic constipation-therapeutic efficacy and satisfaction test (CC-TEST) among patients with chronic constipation. METHODS: Japanese patients with moderate or severe chronic constipation underwent a 4-week remedy. The baseline, 2-week, and 4-week assessments included the CC-TEST, Constipation Scoring System (CSS), Medical Outcome Study Short Form-8 Health Survey (SF-8), and Hospital Anxiety and Depression Scale (HADS). The CC-TEST comprises three domains: (1) symptoms; chronic constipation symptom severity (seven items), defecation status (five items), (2) impact for daily life; dissatisfaction with daily life level (DS; four items), and (3) therapeutic response; therapeutic efficacy measured by patients and medication compliance (four items). RESULTS: Of 201 eligible patients at baseline, 110 completed the 4-week treatment and the survey responses. Cronbach's α values for the stool, defecation, and abdominal symptom subscales, as well as the total symptom score and DS subscale, showed good internal consistency reliability (0.72-0.80). Pearson's r for comparisons between corresponding items (CC-TEST symptoms with CSS, and CC-TEST DS with SF-8 physical and mental component summary scores) was significant. After 4 weeks, scores for symptoms, defecation status, and DS items/subscales notably decreased, with a significant effect size (p < 0.005, Cohen's d; 0.30-1.16). Statistically significant differences emerged between treatment responders and nonresponders using the three responder definitions, in changes in scores for most CC-TEST symptoms, defecation status, and DS items/subscales (p < 0.05). CONCLUSION: CC-TEST demonstrates commendable reliability, convergent and known-group validity, and responsiveness to treatment effects. As a simple, comprehensive, and versatile patient-reported outcome measure, CC-TEST may be well suited for clinical trials and primary care of Japanese patients with chronic constipation.

Comparison of the effects of individual symptoms of gastroesophageal reflux disease co-existing functional dyspepsia on patients' daily lives: A prospective, observational study.

Background and Aim: Patients with gastroesophageal reflux disease (GERD) frequently also have functional dyspepsia (FD) symptoms, which impair their quality of life. However, the magnitude and characteristics of the effects of each symptom on daily life have been unclarified. Using multiple regression analysis, we aimed to clarify these questions. Methods: We enrolled 290 patients from 29 institutions across Japan, in this prospective, observational study. Patients responded to three questionnaires (Gastroesophageal Reflux and Dyspepsia Therapeutic Efficacy and Satisfaction Test [GERD-TEST], Hospital Anxiety and Depression Scale [HADS], and 8-item Short-Form Health Survey [SF-8]) before and after 4 weeks of proton pump inhibitor treatment. Pearson correlation and multiple regression analyses were conducted between symptoms such as typical GERD, epigastric pain syndrome (EPS) and postprandial distress syndrome (PDS) of FD, and aspects of daily life, namely, level of satisfaction with the daily life of GERD-TEST, anxiety and depression score of HADS, and physical and mental component summary of SF-8. Results: Pearson correlation analysis showed a significant correlation in all combinations between GERD/FD-EPS/FD-PDS symptoms and the nine aspects of daily life. However, multiple regression analysis results deviated from these results, with the most significant effects seen in the PDS-symptom subscale (SS) on the five aspects of daily life, that is, dissatisfaction with eating, daily life-SS, anxiety, depression, and mental component summary (MCS) whereas the significant effects in GERD-SS on five aspects of daily life, that is, dissatisfaction for eating, anxiety, depression, physical component summary, and MCS, disappeared. Conclusion: Dealing with co-existing FD symptoms without overlooking them may be important in the management of GERD.

Effect of storage temperature and flash-freezing on salivary microbiota profiles based on 16S rRNA-targeted sequencing.

The sample storage environment affects gut microbial profiles as assessed using 16S rRNA sequencing. However, the influence of storage condition on human salivary microbial profiles has not been well characterized. Here, we performed an observational study to assess the robustness of microbiota profiles in three different storage environments (-80°C after flash-freezing, -80°C, and -15°C; all for 14 days) compared to immediate DNA extraction using the MiSeq Illumina platform. Notably, the 16S rRNA V1-V2 region amplicon sequencing revealed no difference in microbiota profiles between the immediate extraction and each of three storage conditions. An almost perfect correlation was shown between the immediate extraction and the -15°C storage group for relative abundance at the genus and operational taxonomic unit levels. The intraindividual UniFrac distances among storage methods were significantly shorter than those of interindividual distances. None of the amount of extracted DNA, the α-diversity indices, or the relative abundance at the phylum/genus/operational taxonomic unit level differed among storage methods. These findings indicate that a storage temperature of -15°C without flash-freezing may be optimal in terms of cost advantage and simplicity in 16S rRNA sequencing-based salivary microbial research.

Effects of coexisting upper gastrointestinal symptoms on daily life and quality of life in patients with gastroesophageal reflux disease symptoms.

BACKGROUND AND AIM: Gastroesophageal reflux disease (GERD) is a common disease encountered in daily medical care and clinical problem which hampers daily life and reduces quality of life (QOL). The coexistence of GERD-related symptoms with the typical GERD symptoms, such as heartburn or acid regurgitation, and various upper abdominal symptoms is frequently observed in patients with GERD. However, the effect of these coexisting symptoms on the daily life and QOL of patients with GERD has not been clarified. Therefore, the effects of the various upper abdominal symptoms coexisting with GERD on the daily life and QOL of such patients were compared. METHODS: A total of 113 newly diagnosed patients who visited our hospital with typical GERD symptoms were assessed using the modified frequency scale for the symptoms of GERD (MFSSG), gastroesophageal reflux and dyspepsia therapeutic efficacy and satisfaction test (GERD-TEST), and short-form 8-item health survey (SF-8) questionnaires. The "gastroesophageal reflux symptom" (7 items) and "dyspepsia symptom" (7 items) groups were divided into two "typical symptoms" and two "atypical symptoms" for a total of four categories. The Pearson's correlation coefficient and multiple regression analysis were used to evaluate the correlations between each symptom category and dissatisfaction for daily life [eating, sleeping, daily activities, mood, as well as dissatisfaction for daily life-symptom subscale (SS), which is the average of the four items in the GERD-TEST, the physical component summary [PCS] and mental component summary [MCS] of the SF-8, and the influence of each symptom category on the daily life and QOL. RESULTS: The incidences of each symptom category in patients with GERD were high: typical GERD (100%), atypical GERD symptoms (67.3%), typical functional dyspepsia (FD) (71.7%), and atypical FD (75.2%). Pearson's correlation analysis demonstrated significant correlations between each symptom category and living status (dissatisfactions of eating, sleeping, daily activities, daily life-SS) and almost all items in SF-8 (PCS, MCS) (P < 0.05). Multiple regression analysis indicated the largest influences of each symptom category on living status and QOL in descending order: dissatisfaction for eating (atypical FD, typical FD), daily activities (atypical FD, typical FD, typical GERD), mood (atypical FD), daily life-SS (atypical FD, typical FD), PCS (typical FD), and MCS (atypical FD) (P < 0.05). CONCLUSION: Coexisting FD symptoms, particularly atypical FD symptoms, had a large influence on the impairments of daily life and decreases in QOL. Daily medical care of GERD requires attention to coexisting symptoms and their treatment instead of just focusing on the chief complaints by patients.

Clinical features and therapeutic responses to proton pump inhibitor in patients with severe reflux esophagitis: A multicenter prospective observational study.

BACKGROUND AND AIM: In patients with severe erosive reflux disease (ERD; Los Angeles classification grade C/D) who do not undergo endoscopic examination, insufficient strength and duration of proton pump inhibitor (PPI) therapy may lead to complications such as esophageal bleeding and stenosis. Therefore, to provide a safe and effective treatment for gastroesophageal reflux disease (GERD), we investigated the clinical features of patients with severe ERD and their responses to PPI therapy. METHODS: Patients with GERD symptoms received PPI therapy for 4 weeks after endoscopic examination. The patients completed the Gastroesophageal reflux and dyspepsia therapeutic efficacy and satisfaction test questionnaire before and 2 or 4 weeks after PPI treatment. Patient characteristics, presence/absence of coexisting atrophic gastritis (AG) and hiatus hernia (HH), and responses to PPI therapy were compared in patients with GERD among three groups (nonerosive reflux disease, mild ERD [grade A/B], and severe ERD). RESULTS: The severe ERD group had a significantly higher proportion of males, higher body mass index, and longer duration of GERD morbidity. Furthermore, the severe ERD group also had a significantly lower incidence of coexisting AG and higher incidence of HH. There was no difference in the severity of GERD before PPI treatment among the three groups. Unexpectedly, the response to PPI therapy was the best in the severe ERD group. CONCLUSION: Sufficient strength and period of PPI therapy are required, even if the symptoms show early improvement, when treating GERD patients without performing endoscopy, considering the possibility of severe ERD.

The early therapeutic response at 2 weeks is a crucial predictor of proton pump inhibitor-refractory gastroesophageal reflux disease.

BACKGROUND: In recent years, the prevalence of proton pump inhibitor (PPI)-refractory gastroesophageal reflux disease (GERD) has been increasing, posing a clinical obstacle to improving the management of GERD patients. The ability of known predictive factors to explain therapeutic response to PPI remains insufficient. Therefore, we examined whether the addition of early therapeutic response to PPI as an explanatory variable may increase the predictive power for PPI-refractory GERD. METHODS: The severity and therapeutic response of GERD symptoms to PPI were evaluated using the GastroEsophageal Reflux and Dyspepsia Therapeutic Efficacy and Satisfaction Test (GERD-TEST) questionnaire at baseline and at 2 and 4 weeks after treatment. The relevance of the therapeutic effect of PPI at 2 weeks compared to that at 4 weeks was examined in 301 patients with GERD. Independent predictive factors for refractory GERD at 4 weeks of PPI therapy were examined in 182 patients. The effect of various clinical factors, including the early response to PPI, was assessed using multiple regression analysis. RESULTS: The number of PPI-therapy responders increased significantly with the duration of treatment (p < 0.0001). The response to PPI therapy at 2 weeks was significantly correlated with that at 4 weeks (p < 0.0001). Multiple regression analysis revealed that the therapeutic response to PPI at 2 weeks was by far the strongest predictor of the therapeutic effect at 4 weeks among all clinical factors. CONCLUSIONS: Medication change for PPI-refractory GERD at 2 weeks may be an efficacious therapeutic strategy to improve patients' quality of life.

Therapeutic strategy for the patients with coexisting gastroesophageal reflux disease and postprandial distress syndrome of functional dyspepsia.

BACKGROUND AND AIM: Gastroesophageal reflux disease (GERD) and functional dyspepsia (FD) frequently overlap. However, no accepted treatment has yet been established for such patients. This study was conducted to identify an adequate initial treatment for patients with GERD accompanied by the postprandial distress syndrome type of FD (FD-PDS). METHODS: Of the 150 patients newly diagnosed with GERD who visited our clinic, 53 patients with the typical symptoms of both GERD and FD-PDS were assessed using the modified frequency scale for the symptoms of GERD and the gastroesophageal reflux and dyspepsia therapeutic efficacy and satisfaction test questionnaires. Of those, 42 patients who completed 4 weeks of treatment were analyzed. We compared the treatment responses between the 21 patients who received proton pump inhibitor (PPI) monotherapy and 21 patients who received a PPI in combination with the prokinetic drug acotiamide. RESULTS: Assessment of the two questionnaires revealed a marked improvement of both GERD and FD symptom scores after 4 weeks of treatment in both groups. However, there were no significant differences in any GERD or FD symptom scores at baseline, after 4 weeks of treatment and in the symptom score change between the two different treatment groups. CONCLUSION: The results of this retrospective study suggest no benefit of PPI-prokinetic combination versus PPI monotherapy in adult patients with FD-GERD overlap; therefore, PPI monotherapy could be an adequate initial treatment for such patients.

Correction to: Proton pump inhibitor monotherapy is effective to attenuate dyspepsia symptoms associated with gastroesophageal reflux disease: a multicenter prospective observational study.

In the original publication of this article, Tables 2, 3, 4, 5 and 6 were published incorrectly. The correct tables are given below.

Proton pump inhibitor monotherapy is effective to attenuate dyspepsia symptoms associated with gastroesophageal reflux disease: a multicenter prospective observational study.

BACKGROUND AND AIM: Gastroesophageal reflux disease (GERD) and functional dyspepsia (FD) are frequently overlapped. However, no treatment strategies have been established yet for such patients. This study compared the effects of proton pump inhibitor (PPI) treatment in patients with GERD-associated FD among three groups with varying severity levels of GERD symptoms. METHODS: The patients with GERD and FD symptoms received PPI treatment for 4 weeks after endoscopy, and the severity of the symptoms and responses to treatment were evaluated at before and after 4 weeks of treatment using the Gastroesophageal Reflux and Dyspepsia Therapeutic Efficacy and Satisfaction Test (GERD-TEST). The patients were divided into three groups in accordance with the severity of the GERD symptoms as assessed by the GERD symptom subscale (SS) scores of pre-treatment. RESULTS: Data from 233 cases of 40 mild, 151 moderate and 42 severe symptoms were analyzed. Analysis of the pre-treatment scores for each symptom revealed that a higher GERD-SS score was significantly associated with higher scores on any kind of FD score. Four weeks of PPI treatment significantly and markedly alleviated any of GERD/FD symptoms. Most importantly, change in the score for each symptom after 4 weeks of treatment relative to the pre-treatment score was significantly greater in the groups with more severe GERD-SS. CONCLUSION: FD symptoms associated with more severe GERD symptoms are supposed to be acid-related dyspepsia, and PPI monotherapy is recommended as the treatment of first choice in such patients.

Competency assessment for gastric endoscopic submucosal dissection using an endoscopic part-task training box.

BACKGROUND: Objective assessment of endoscopist competency is important. Recently, the endoscopic part-task training box (Thompson Endoscopic Skills Trainer [TEST]) was developed to assess endoscopist competency. We aimed to evaluate the ability of the TEST to assess competency during endoscopic procedures, especially endoscopic submucosal dissection (ESD). METHODS: Twenty-three physicians were included in this study. Correlations between TEST scores and the following factors were evaluated: years of endoscopic experience, number of esophagogastroduodenoscopies (EGDs) performed, number of colonoscopies (CSs) performed, cecal intubation rate, number of gastric ESDs performed, gastric ESD procedure time/lesion size (min/mm2), and gastric ESD self-completion rate. Also, correlation coefficients between the number of gastric ESDs performed and each of gastric ESD procedure time/lesion size and gastric ESD self-completion rate were calculated. RESULTS: TEST scores showed strong correlations to different factors: years of experience in endoscopy: 0.957 (p < 0.01); number of EGDs: 0.947 (p < 0.01); number of CSs: 0.947, (p < 0.01); number of gastric ESDs: 0.924 (p < 0.01); gastric ESD procedure time/lesion size: - 0.9 (p < 0.01); self-completion rate of gastric ESDs: 0.857 (p < 0.005). The number of gastric ESDs performed was not more strongly correlated to procedure time of gastric ESDs or self-completion rate of gastric ESDs compared to TEST scores (- 0.824 (p < 0.01) and 0.704 (p < 0.05), respectively). TEST scores of endoscopists with a cecal intubation rate ≥ 90% were > 380, while the scores of physicians with a gastric ESD self-completion rate ≥ 90% were > 700. CONCLUSIONS: TEST score correlates with both basic and advanced endoscopic procedures. TEST is therefore a promising option for assessing endoscopist competency, and might be useful for providing threshold scores as competency markers for specific endoscopic procedures such as gastric ESD.

Foveolar gastric metaplasia presenting as a duodenal tumor with an atypical appearance: a case report.

BACKGROUND: Foveolar gastric metaplasia of the duodenum is a frequent but not as yet considered correlate of endoscopically detected duodenal polyps. The majority of foveolar gastric metaplasias associated with polyps presented a typical benign endoscopic appearance and they were diagnosed by biopsy. Here we report a case of a surgical-resected foveolar gastric metaplasia manifesting as a duodenal tumor with an atypical appearance. CASE PRESENTATION: An asymptomatic 56-year-old Asian man who presented with a foveolar gastric metaplasia of atypical appearance and had previously undergone esophagogastroduodenoscopy was referred to our hospital. A biopsy revealed a normal duodenum with an inflamed mucosa. Narrow band imaging with magnifying endoscopy revealed normal microvessels with normal micromucosa, which indicated non-neoplasia. Endoscopic ultrasonography using a miniature probe system (20 MHz) revealed a hypoechoic mass with multiple anechoic lesions (16-mm diameter) located in the mucosal layer. The lesion was excised via laparotomy assisted by endoscopic techniques similar to endoscopic submucosal dissection. The pathology indicated foveolar gastric metaplasia. CONCLUSIONS: Foveolar gastric metaplasia can present as a duodenal tumor. We identified two important clinical issues. First, foveolar gastric metaplasia can present as a duodenal tumor with an atypical benign appearance. Second, both endoscopic ultrasonography and narrow band imaging are useful techniques to increase the diagnostic rate of this condition.

Prophylactic hemostasis for postpolypectomy mucosal defect using endoclip under infrared imaging endoscopy.

The efficacy of prophylactic hemostasis with endoclips after polypectomy is still controversial. The purpose of this study is to evaluate the efficacy of prophylactic hemostasis for postpolypectomy mucosal defects using endoclips under infrared imaging. Patients with colon polyps who were endoscopically treated at Jikei University Aoto Hospital were retrospectively reviewed to compare the delayed bleeding rate in the infrared imaging group with the conventional imaging group. A total of 813 colon polyps in 416 patients were endoscopically treated from July 2003 to November 2006. The overall postpolypectomy bleeding rate in the infrared imaging group was shown to be significantly lower than in the conventional imaging group. The postpolypectomy bleeding from the endoclip site was also significantly lower in the infrared imaging group than in the conventional imaging group. Even the number of applied endoclips was significantly fewer in the infrared group than the conventional group. The prophylactic use of endoclips with infrared imaging effectively reduced the postpolypectomy bleeding with fewer clip applications.

Predicting 5-FU sensitivity using human colorectal cancer specimens: comparison of tumor dihydropyrimidine dehydrogenase and orotate phosphoribosyl transferase activities with in vitro chemosensitivity to 5-FU.

BACKGROUND: In tumor cells, the enzyme orotate phosphoribosyl transferase (OPRT) contributes to 5-fluorouracil (5-FU) phosphorylation and another enzyme, dihydropyrimidine dehydrogenase (DPD), is associated with 5-FU catabolic action. We measured OPRT and DPD activities and, to determine whether their levels might serve as indicators of 5-FU sensitivity, simultaneously assayed in vitro chemosensitivity to 5-FU. METHODS: Tissue specimens were obtained from colorectal cancer patients and in vitro chemosensitivity was tested using fluorescein diacetate assay (FDA) or histoculture drug response assay (HDRA). DPD and OPRT activities were measured by radioassay. RESULTS: The chemosensitivity assay was performed on 62 colorectal cancer specimens. Results were evaluable in 29 of 30 cases (96.7%) for FDA and 30 of 32 cases (98.3%) for HDRA. The positive sensitivity rate was 37.9% by FDA assay and 30% by HDRA assay. In positive specimens, the mean DPD activity was 44.9 +/- 32.6 pmol/min per mg protein, and in negative specimens, it was 53.8 +/- 33.7 pmol/min per mg protein ( P= 0.875). In contrast, the mean OPRT value was significantly higher in positive specimens (0.418 +/- 0.180 nmol/min per mg protein) than in negative specimens (0.325 +/- 0.153 nmol/min per mg protein; P < 0.05). The chemosensitivity test proved positive in 60% of the specimens with ORPT activity of 0.413 or above and 50% of those with DPD activity of 30 or below. Of the patient specimens showing OPRT activity of 0.413 or above and DPD activity of 30 or below, 88.9% were positive for 5-FU sensitivity, suggesting the possibility that the combination of these two levels may be predictive of 5-FU positive sensitivity. CONCLUSION: DPD and OPRT activities within cancer cells may predict positive sensitivity to 5-FU.