Simultaneous Expression of CD70 and POSTN in Cancer-Associated Fibroblasts Predicts Worse Survival of Colorectal Cancer Patients.

Colorectal cancer (CRC) is one of the most common gastrointestinal cancers worldwide, with high morbidity and mortality rates. The evidence for the tumor-supporting capacities of cancer-associated fibroblasts (CAFs) that modulate cancer cell proliferation, invasion, metastasis, and tumor immunity, including in CRC, has been attracting attention. The present study examined the expression status of CD70 and POSTN in CRC and analyzed their association with clinicopathological features and clinical outcomes. In the present study, in total 15% (40/269) and 44% (119/269) of cases exhibited CD70 and POSTN expression on CAFs, respectively. Co-expression of CD70 and POSTN was detected in 8% (21/269) of patients. Fluorescent immunohistochemistry identified the co-expression of CD70 and POSTN with FAP and PDPN, respectively. ACTA2 was not co-expressed with CD70 or POSTN in CRC CAFs. CRC with CD70+/POSTN+ status in CAFs was significantly associated with distant organ metastasis (p = 0.0020) or incomplete resection status (p = 0.0011). CD70+/POSTN+ status tended to associate with advanced pT stage (p = 0.032) or peritoneal metastasis (p = 0.0059). Multivariate Cox hazards regression analysis identified CD70+/POSTN+ status in CAFs [hazard ratio (HR) = 3.78] as a potential independent risk factor. In vitro experiments revealed the activated phenotypes of colonic fibroblasts induced by CD70 and POSTN, while migration and invasion assays identified enhanced migration and invasion of CRC cells co-cultured with CD70- and POSTN-expressing colonic fibroblasts. On the basis of our observations, CD70 and POSTN immunohistochemistry can be used in the prognostication of CRC patients. CRC CAFs may be a promising target in the treatment of CRC patients.

Gastroesophageal Reflux Disease: Pathophysiology and New Treatment Trends.

Gastroesophageal reflux disease (GERD) is caused by the reflux of gastric contents into the esophagus due to a decline in esophageal clearance and anti-reflux barrier mechanisms. Mucosal injury is caused by a combination of gastric juice directly damaging the esophageal mucosa and the immune and inflammatory mechanism in which inflammatory cytokines released from the esophageal mucosal epithelium cause neutrophil migration, triggering inflammation. Gastric secretion inhibitors are the first-line treatment for GERD, but they can be combined with prokinetic agents and Chinese herbal remedies. However, pharmacotherapy cannot improve anatomical problems or prevent physical causes of GERD, such as reflux of non-acidic contents. Therefore, surgery can be warranted, depending on the pathology. Intraluminal endoscopic therapy, which is both less invasive and more effective than surgery, was recently developed and applied in Europe and the United States. In Japan, intraluminal endoscopic therapies, such as anti-reflux mucosectomy, anti-reflux mucosal ablation, and endoscopic submucosal dissection, for GERD have been independently developed.

Characterization of colorectal cancer by hierarchical clustering analyses of five immune cell markers.

The present study analyzed the expression of five independent immunohistochemical markers, CD4, CD8, CD66b, CD68, and CD163, on immune cells within the colorectal cancer (CRC) tumor microenvironment (TME). Using hierarchical clustering, patients were successfully classified according to significant associations with clinicopathological features and/or survival. Patients with mismatch repair-proficient (pMMR) CRC were categorized into four groups with survival differences (p = 0.0084): CD4Low , CD4High , MΦHigh , and CD8Low . MΦHigh tumors showed significantly higher expression of CD47 (p < 0.0001), a phagocytosis checkpoint molecule. These tumors contained significantly greater numbers of PD-1+ (p < 0.0001), TIM-3+ (p < 0.0001), and SIRPA+ (p < 0.0001) immune cells. Notably, 10% of the patients with pMMR CRC expressed PD-L1 (CD274) on tumor cells with significantly worse survival (p = 0.00064). The Cox proportional hazards model identified MΦ High (hazard ratio [HR] = 2.02, 95%, p = 0.032), CD8Low (HR = 2.45, p = 0.011), and tumor PD-L1 expression (HR = 2.74, p = 0.0061) as potential risk factors. PD-L1-PD-1 and/or CD47-SIRPA axes targeting immune checkpoint therapies might be considered for patients with pMMR CRC according to their tumor cells and tumor immune microenvironment characteristics.

Urgent colonoscopy is not necessary in case of colonic diverticular bleeding without extravasation on contrast-enhanced computed tomography.

BACKGROUND AND AIMS: Acute lower gastrointestinal bleeding (ALGIB) increase with age and the administration of antiplatelet drugs. Colonic diverticular bleeding (CDB) is the most common cause of ALGIB, and endoscopic hemostasis is an effective treatment for massive CDB. But in patients without extravasation on contrast-enhanced computed tomography (CECT), the efficacy of urgent colonoscopy (UCS) is controversial from the point of the clinical course, including rebleeding rate. We aimed to establish a potential strategy including UCS for CDB patients without extravasation on CECT. PATIENTS AND METHODS: Patients from two centers treated for CDB without extravasation on CECT between July 2014 and July 2019 were retrospectively identified (n = 282). Seventy-four underwent UCS, and 208 received conservative management. We conducted two analyses. The first analysis investigates the risk factors of rebleeding rate within 5 days after administration (very early rebleeding), and no UCS (NUCS) was not the independent factor of the very early rebleeding. The second analysis is whether UCS positively influenced the clinical course after hospitalization. RESULTS: The prevalence of very early rebleeding and early rebleeding (6-30 days from admission), patients requiring blood transfusion within 0-5 days and 6-30 days post-admission, and duration of hospitalization were examined as clinical course factors between UCS and NUCS group. There was no significant difference between the UCS and non-UCS groups in the clinical course factors. UCS for the CDB patients without extravasation was not improved rebleeding rate and clinical course. CONCLUSIONS: UCS is not necessary in case ofCDB patient without extravasation on CECT.

Relationships between body mass index and constipation, gastroesophageal reflux disease, stool forms based on the Bristol Stool Form Scale, and education level: results from an internet survey in Japan.

Detailed evaluations of body mass index (BMI) and stool form based on the Bristol Stool Form Scale (BSFS) in individuals with constipation, gastroesophageal reflux disease (GERD), and concomitant constipation and GERD have not been performed in Japan. This study was an internet survey conducted to examine the relationships between BMI and constipation, GERD, stool forms based on the BSFS, and education level. This internet-based survey recruited participants from general public survey panels. 10,000 individuals meeting the eligibility criteria were enrolled. Questions included demographics, medical data, and assessments based on validated measures for constipation and GERD. BMI was significantly lower in males with versus without constipation. BMI was significantly higher with GERD both males and females. Mean BMI increased from the BSFS-1/2 group through the BSFS-3/4/5 to the BSFS-6/7 groups in both sexes. BMI was highest in individuals with a maximum education level of junior high school and second highest in individuals completing high school. This is the first real-world survey that closely examines the relationship between BMI and stool forms of individuals in Japan. When the BMI increased, stool forms varied from hard to watery in Japanese people. BMI was related with education level in Japan. (Trial registration: UMIN000039688).

A case report of contrast-enhanced harmonic ultrasonography for the diagnosis of an esophageal duplication cyst.

A 54-year-old man was referred to our hospital because of a suspected esophageal submucosal tumor on upper gastrointestinal radiography. Contrast-enhanced computed tomography showed a 52 mm homogeneous mass attached to the lower thoracic esophagus. Esophagogastroduodenoscopy revealed a 50 mm submucosal tumor in the lower esophagus, and endoscopic ultrasonography (EUS) showed a continuous hypoechoic lesion in the esophageal muscularis propria. Contrast-enhanced harmonic EUS revealed a non-echogenic area. T1 and T2 magnetic resonance imaging revealed a high-signal lesion. Based on imaging studies, an esophageal duplication cyst was diagnosed. Although asymptomatic, the patient underwent video-assisted thoracic surgery because of the possibility of rupture and the appearance of symptoms due to a future infection or enlargement, although this was not noted before. In our case, the esophageal duplication cyst appeared as a hypoechoic mass, requiring differentiation from submucosal tumor other than the cyst. Histologically, the cyst was covered by two layers of muscle covered by the chorioepithelial columnar epithelium. EUS fine-needle aspiration is effective in diagnosing submucosal tumor but also carries the risk of infection. Contrast-enhanced ultrasonography was used in this case to observe the interior and reach a preoperative diagnosis. Contrast-enhanced harmonic EUS appears to be effective in examining the interior of submucosal tumor lesions noninvasively.

Stromal POSTN Enhances Motility of Both Cancer and Stromal Cells and Predicts Poor Survival in Colorectal Cancer.

Evidence for the tumor-supporting capacities of cancer-associated fibroblasts (CAFs) has rapidly been accumulating. To uncover clinicopathological importance of periostin (POSTN) expression in colorectal cancer (CRC), the present study immunohistochemically examined its expression status. Furthermore, to reveal its mechanisms involved, molecular experiments were performed. In CRC tissues, 44% of the cases (119/269) exhibited POSTN expression in the CAFs. In contrast, CRC cells expressed POSTN at almost undetectable levels. Survival analyses identified that patients with POSTN-positive CRC had a significantly worse 5-year survival rate (63.2% vs. 81.2%; p = 0.011). Univariate analyses revealed that POSTN positivity was associated with peritoneal (p = 0.0031) and distant organ metastasis (p < 0.001). Furthermore, immunohistochemical analyses identified a significant association between POSTN and p53 complete loss status in CRC cells. Decorin and fibroblast activation protein expression in CAFs was also associated with POSTN. POSTN significantly enhanced the migration of both CRC cells and fibroblasts with FAK and AKT or STAT3 activation, and co-culture assays demonstrated the communication between CRC cells and fibroblasts, which enhanced STAT3 activation in fibroblasts. On the basis of our results, we speculated that stromal POSTN accelerated metastasis via stromal remodeling capacity and activated the migration of both tumor and stromal cells.

A Vonoprazan, Clarithromycin, and Metronidazole Regimen as Helicobacter pylori Eradication Therapy for Patients with Penicillin Allergy in Light of Clarithromycin Resistance.

Objective Vonoprazan (VPZ), clarithromycin (CAM), metronidazole (MNZ) and VPZ, MNZ, and sitafloxacin (STFX) regimen are all established Helicobacter pylori eradication therapies for patients with penicillin allergy in Japan. However, no study has assessed the efficacy of a VPZ, CAM, and MNZ (VCM) regimen in patients with clarithromycin resistance (CAM-R). We therefore assessed the efficacy of a VCM regimen for treating H. pylori infection in patients with CAM-R and penicillin allergy. Methods Fifty-three patients with penicillin allergy who received H. pylori eradication therapy were retrospectively analyzed. Eight patients received a 7-day proton-pump inhibitor, CAM, and MNZ (PCM) regimen; 35 patients [11 CAM-R, and 10 with clarithromycin sensitivity (CAM-S)] received 7-day VCM regimens; and 10 patients received 7-day VPZ, MNZ, and STFX (VMS) regimens. A 13C-urea breath test was used to determine eradication. The efficacy of eradication was evaluated via both intention-to-treat (ITT) and per-protocol (PP) analyses. Results According to ITT and PP analyses, eradication rates (ERs) with PCM, VCM, and VMS therapies were 50.0% and 50.0%, 94.3% and 100%, and 90% and 90%, respectively. Treatment was successful in all patients with CAM-S. For patients with CAM-R, treatment was successful in 10 patients, and 1 patient discontinued treatment owing to an adverse event. According to ITT and PP analyses, ERs were 90.9% and 100% in CAM-R, and were 100% and 100% in CAM-S, respectively. Conclusion The VCM regimen for H. pylori eradication may be a viable candidate therapy for patients with penicillin allergy, regardless of CAM-R.

A case report of olmesartan-associated sprue-like enteropathy: Diagnosis and healing confirmed by capsule endoscopy.

Herein, we describe a case of olmesartan-related sprue-like enteropathy in which improvement in villous atrophy was confirmed by small-bowel capsule endoscopy (CE). We successfully treated a 66-year-old man with a chief complaint of loose diarrhea. The patient had persistent watery diarrhea 10 times a day and experienced a weight loss of 9 kg in 3 months. An abdominal computed tomography scan showed fluid retention in the small intestine. Blood test results revealed no inflammatory reaction. Esophagogastroduodenoscopy detected villous atrophy in the stomach and duodenum. Moreover, small-bowel CE showed villous atrophy in about two-thirds of the small intestine. Based on other examinations, hyperthyroidism, intestinal tuberculosis, intestinal amyloidosis, and intestinal malignant lymphoma were ruled out. Therefore, the patient was suspected of having an olmesartan-related sprue-like disease. Early after discontinuation of medication, diarrhea symptoms improved, and a repeat CE indicated improvements in small intestinal villous atrophy. Since the patient had been administered olmesartan for a long time and CE showed villous atrophy throughout the small bowel, we suspected him of having the olmesartan-associated sprue-like disease. The findings of gastric mucosa atrophy on esophagogastroduodenoscopy may lead to an early diagnosis of this disease. Olmesartan-related sprue-like enteropathy should be considered as a differential diagnosis in patients with chronic severe watery diarrhea.

A case of ulcerative colitis-related postoperative enteritis treated with granulocyte and monocyte apheresis.

A 46-year-old man, receiving continuous steroid therapy for refractory ulcerative colitis with an insufficient response to anti-tumor necrosis factor-α therapy, presented with left buttock pain. He was diagnosed with steroidal left femoral head necrosis, and total proctocolectomy with permanent ileostomy was performed. At 6 months postoperatively, the patient developed general fatigue, abdominal pain, and severe ileostomy diarrhea. Computed tomography revealed continuous intestinal edema from the descending duodenal leg to the upper jejunum. Gastrointestinal endoscopy revealed deep ulcers, coarse mucosa, and duodenal erosion. Based on clinical progress, findings, and pathology, the patient was diagnosed with ulcerative colitis-related postoperative enteritis. Although 5-aminosalicylic acid treatment was initiated, his symptoms persisted, bloody diarrhea from colostomy was observed. Subsequently, granulocyte and monocyte apheresis treatment was added. Symptoms and endoscopic findings improved with granulocyte and monocyte apheresis. Azathioprine was introduced as maintenance therapy, and no sign of recurrence was observed. Although ulcerative colitis-related postoperative enteritis has no definitive treatment, granulocyte and monocyte apheresis may be considered for initial treatment.

Small-Intestinal Metastasis from Lung Carcinoma.

A 62-year-old man was referred to our hospital because of abdominal pain. Computed tomography revealed an approximately 7-cm-diameter tumor in the left abdomen with metastatic lymph nodes, an approximately 1-cm-diameter round tumor in contact with the subclavian artery in the apical lobe of the right lung, and mediastinal lymph node enlargement in contact with the superior vena cava. Esophagogastroduodenoscopy and colonoscopy revealed no abnormalities. Double-balloon endoscopy revealed a whole circumferential ulcer in the jejunum approximately 20 cm from the ligament of Treitz. Biopsy analysis of an ulcer specimen revealed a poorly differentiated carcinoma. Immunohistochemical staining of the specimen showed that it was positive for thyroid transcription factor 1 and cytokeratin 7 and negative for cytokeratin 20, GATA-binding protein 3, caudal-type homeobox protein 2, and paired box 8. Positron emission tomography revealed positive findings in the small-intestinal tumor, nearby mesenteric lymph nodes, lymph nodes around the abdominal aorta, lung tumor, and mediastinal lymph node in the apical lobe of the right lung. Accordingly, the patient was diagnosed as having a lung carcinoma with small-intestinal metastasis (T1b, N3, M1c; cStage IVB). Pathological examination helped distinguish the primary small-intestinal tumor from the metastatic small-intestinal tumor and detect the tumor origin.

Gastric Plexiform Fibromyxoma Resected Using Nonexposed Endoscopic Wall-Inversion Surgery: A Case Report.

Gastric plexiform fibromyxoma is extremely rare. In our case, upper gastrointestinal endoscopy of a 41-year-old woman patient revealed a 1-cm submucosal tumor (SMT) in the greater curvature of the lower body of the stomach. On contrast-enhanced computed tomography, the tumor was hypervascular in the arterial phase with continuous enhancement in the post-venous phase. On endoscopic ultrasonography, it had a low echo pattern. The preoperative diagnosis was a gastric SMT with a rich vasculature; however because the biosy specimen did not contain tumor tissue, a malignant tumor could not be excluded. The patient underwent nonexposed endoscopic wall-inversion surgery (NEWS), and the tumor was completely resected. Immunohistochemical examination revealed that the tumor was positive for D2-40 and α-smooth muscle actin, but negative for c-kit, discovered on gastrointestinal stromal tumor-1, desmin, S100, Melan-A, signal transducer and activator of transcription 6, insulinoma-associated protein 1, CXCL13, ETS transcription factor, follicular dendritic cell, anaplastic lymphoma kinase, human melanoma black, h-caldesmon, and CD1a, 10, 21, 23, 31, 34, 68, and 163. Approximately, 1-2% of the tumor cell nuclei were Ki-67-positive. Finally, we diagnosed the tumor as a plexiform fibromyxoma. In conclusion, NEWS is an effective method for the treatment of SMTs with a diameter of <3 cm.

Effectiveness of second-look endoscopy after gastric endoscopic submucosal dissection in patients taking antithrombotic agents: a multicenter propensity score matching analysis.

BACKGROUND: The risk of bleeding after gastric endoscopic submucosal dissection (ESD) in antithrombotic agent users has increased, and its management remains a problem. Second-look endoscopy (SLE) following gastric ESD in antithrombotic agent users may be effective in preventing delayed bleeding, but this requires elucidation. Therefore, this study aimed to investigate the efficacy of SLE in reducing bleeding after gastric ESD in patients receiving antithrombotic agents. METHODS: This retrospective cohort study was conducted at 19 referral hospitals in Japan. A total of 1,245 patients who were receiving antithrombotic agents underwent gastric ESD between January 2013 and July 2018. The incidence of delayed bleeding was compared between SLE and non-SLE groups using propensity score matching analysis. RESULTS: Overall, 858 patients (SLE group, 657 patients; non-SLE group, 201 patients) were analyzed. After matching, 198 pairs were created. Delayed bleeding occurred in 10 patients (5.1%) in the SLE group and 16 patients (8.1%) in the non-SLE group [odds ratio (OR) 0.605, 95% confidence interval (CI) 0.23-1.46, p = 0.310]. In the subgroup analysis, SLE reduced the incidence of delayed bleeding in patients receiving heparin bridging therapy (6.3% and 40.0%, respectively; p = 0.004). In the SLE group, prophylactic coagulation did not significantly reduce delayed bleeding compared to the no treatment group (14.6% and 8.6%, respectively; p = 0.140). CONCLUSIONS: SLE was ineffective in reducing bleeding after gastric ESD in antithrombotic agent users, overall. A prospective comparative study is warranted to definitively evaluate the effectiveness of SLE in reducing bleeding in high-risk patients.

Risk factors and prediction of bleeding after gastric endoscopic submucosal dissection in patients on antithrombotic therapy: newly developed bleeding prediction application software, SAMURAI model.

Bleeding after gastric endoscopic submucosal dissection (ESD) remains problematic, especially in patients receiving antithrombotic therapy. Therefore, this study aimed to identify the risk factors. In this retrospective study, patients (n = 1,207) who underwent gastric ESD while receiving antithrombotic therapy were enrolled at Osaka Medical and Pharmaceutical University Hospital and 18 other referral hospitals in Japan. Risks of post-ESD bleeding were calculated using multivariable logistic regression. The dataset was divided into a derivation cohort and a validation cohort. We created a prediction model using the derivation cohort. The accuracy of the model was evaluated using the validation cohort. Post-ESD bleeding occurred in 142 (11.8%) participants. Multivariable analysis yielded an odds ratio of 2.33 for aspirin, 4.90 for P2Y12 receptor antagonist, 1.79 for cilostazol, 0.95 for other antithrombotic agents, 6.53 for warfarin, 5.65 for dabigatran, 7.84 for apixaban, 10.45 for edoxaban, 6.02 for rivaroxaban, and 1.46 for heparin bridging. The created prediction model was called safe ESD management using the risk analysis of post-bleeding in patients with antithrombotic therapy (SAMURAI). This model had good predictability, with a C-statistic of 0.77. In conclusion, use of the SAMURAI model will allow proactive management of post-ESD bleeding risk in patients receiving antithrombotic therapy.

The Complete Loss of p53 Expression Uniquely Predicts Worse Prognosis in Colorectal Cancer.

p53 immunohistochemistry is considered an accurate surrogate marker reflecting the underlying TP53 mutation status and has utility in tumor diagnostics. In the present study, 269 primary CRCs were immunohistochemically evaluated for p53 expression to assess its utility in diagnostic pathology and prognostication. p53 expression was wild-type in 59 cases (23%), overexpressed in 143 cases (55%), completely lost in 50 cases (19%), and cytoplasmic in 10 cases (4%). p53 immunoreactivity was associated with tumor size (p = 0.0056), mucus production (p = 0.0015), and mismatch repair (MMR) system status (p < 0.0001). Furthermore, among CRCs with wild-type p53 expression, a significantly higher number of cases had decreased CDX2 than those with p53 overexpression (p = 0.012) or complete p53 loss (p = 0.043). In contrast, among CRCs with p53 overexpression, there were significantly fewer ALCAM-positive cases than p53 wild-type cases (p = 0.0045). However, no significant association was detected between p53 immunoreactivity and the "stem-like" immunophenotype defined by CDX2 downregulation and ALCAM-positivity. Multivariate Cox hazards regression analysis identified tubular-forming histology (hazard ratio [HR] = 0.17, p < 0.0001), younger age (HR = 0.52, p = 0.021), and female sex (HR = 0.55, p = 0.046) as potential favorable factors. The analysis also revealed complete p53 loss (HR = 2.16, p = 0.0087), incomplete resection (HR = 2.65, p = 0.0068), and peritoneal metastasis (HR = 5.32, p < 0.0001) as potential independent risk factors for patients with CRC. The sub-cohort survival analyses classified according to chemotherapy after surgery revealed that CRC patients with wild-type p53 expression tended to have better survival than those with overexpression or complete loss after chemotherapy. Thus, immunohistochemistry for p53 could be used for the prognostication and chemotherapy target selection of patients with CRC.

SPATA18 Expression Predicts Favorable Clinical Outcome in Colorectal Cancer.

Dysregulation of mitochondrial quality control has been reported to be associated with cancer and degenerative diseases. SPATA18 (spermatogenesis-associated 18, also known as Mieap) encodes a p53-inducible protein that can induce lysosome-like organelles within mitochondria that eliminate oxidized mitochondrial proteins and has tumor suppressor functions in mitochondrial quality control. In the present study, 268 primary colorectal cancers (CRCs) were evaluated immunohistochemically for SPATA18 expression to assess its predictive utility and its association with cellular proliferation activity. Furthermore, the association with p53 immunoreactivity, a surrogate marker for TP53 mutation, was analyzed. Non-neoplastic colonic mucosa showed cytoplasmic SPATA18 expression. Seventy-two percent of the lesions (193/268) displayed high SPATA18 expression in the cytoplasm of CRC cells. Univariate analyses revealed significant associations between SPATA18 expression and tumor size (p < 0.0001), histological differentiation (p = 0.0017), and lymph node metastasis (p = 0.00039). The log-rank test revealed that patients with SPATA18-high CRCs had significantly better survival than SPATA18-low patients (p < 0.0001). Multivariate Cox hazards regression analysis identified tubular-forming histology (hazard ratio [HR] = 0.25), age < 70 years (HR = 0.50), and SPATA18-high (HR = 0.55) as potential favorable factors. Lymph node metastasis (HR = 1.98) and peritoneal metastasis (HR = 5.45) were cited as potential independent risk factors. Cellular proliferation activity was significantly higher in SPATA18-high tumors. However, no significant correlation was detected between SPATA18 expression and p53 immunoreactivity or KRAS/BRAF mutation status. On the basis of our observations, SPATA18 immunohistochemistry can be used in the prognostication of CRC patients.

Background factors involved in the epidemiology of functional constipation in the Japanese population: a cross-sectional study.

BACKGROUND: Functional constipation (FC), a functional bowel disorder with symptoms of constipation, has considerable impact on quality of life. As data regarding its prevalence and epidemiology are lacking, this study aimed to evaluate the prevalence, population composition, lifestyle, quality of life, and clinical characteristics of these individuals by comparing people with and without FC. These parameters were also compared among individuals with strong and weak awareness of constipation. METHODS: An internet survey was conducted among 10,000 individuals aged 20-69 years from the general Japanese population; they were registered with an internet survey company. The following data were obtained: age, sex, educational history, occupation, residence, history of other diseases, lifestyle (including smoking/drinking habits using the Japanese Health Practice Index, medication use, symptoms of constipation according to the Rome III criteria, stool types according to the Bristol stool scale, and use of laxatives, including the place of purchase and cost per month or acceptable cost per month. The 8-item Short Form Health Survey Questionnaire was also used; FC was diagnosed based on Rome III criteria. All respondents were classified according to their awareness of constipation (i.e. strong or weak), and their characteristic features were compared. RESULTS: The data of 3000 respondents were evaluated; 262 (8.7%) had FC, which was common among older adults, women, and homemakers. FC was associated with changes in the frequency of bowel movement, sensation of incomplete or scanty evacuation, and the use of manual maneuvers; these are consequential clinical symptoms of FC. These individuals frequently skipped breakfast, had insufficient sleep, had more severe constipation, and had purchased laxatives in pharmacies or online more often than those without FC. A strong awareness of constipation was significantly more prevalent among women and homemakers. A history of anemia and cardiovascular disease was significantly more frequent in the strong awareness group, whereas a history of hypertension was more frequent in the weak awareness group. CONCLUSIONS: Appropriate and comprehensive management should be provided for FC, based on the understanding of its characteristic features and considering the symptoms and lifestyle.

Overlap Between Constipation and Gastroesophageal Reflux Disease in Japan: Results From an Internet Survey.

BACKGROUND/AIMS: Detailed evaluations of overlapping constipation and gastroesophageal reflux disease (GERD) have not been conducted in Japan. The REACTION-J2 study examined the overlap of these diseases in Japan. METHODS: This internet-based survey recruited participants from general public survey panels. Questions included demographic and medical data and assessments based on validated measures for constipation and GERD. Associations between background factors affecting constipation/GERD overlap, disease measures, and treatment were also evaluated. RESULTS: Among 10 000 survey responses received, functional constipation (Rome IV diagnostic criteria) was reported by 439 participants; chronic constipation (Japanese guidelines) by 3804 participants; and subjective constipation symptoms by 2563 participants. The number of participants with constipation/GERD overlap ranged from 73 to 1533 depending on the criteria used. Regardless of the definition used, all GERD groups had significantly higher odds of being constipated than non-GERD participants: the OR (95% CI) for all 9 combinations of definitions ranged between 1.56 (1.21, 2.01) and 2.67 (2.44, 2.92) (all P ≤ 0.001). Straining, hard stools, and sensations of incomplete evacuation and anorectal obstruction/blockage, according to chronic constipation criteria, were common. Participants with constipation/GERD overlap had poorer quality of life (P < 0.001) and worse GERD symptom scores (P < 0.001). The frequency of abnormal stools was highest (P < 0.001) in the constipation/GERD overlap group. In the overlap group, 52.4% and 26.0% used gastric and constipation medication, respectively. CONCLUSION: Individuals with constipation/GERD overlap tend to have worsened symptoms and quality of life.

Internet Survey of Japanese Patients With Chronic Constipation: Focus on Correlations Between Sleep Quality, Symptom Severity, and Quality of Life.

BACKGROUND/AIMS: Chronic constipation and lifestyle factors can affect sleep quality. We evaluated the relationship between chronic constipation and sleep in the Japanese population. METHODS: This cross-sectional internet-based survey included 3000 subjects with constipation, classified according to sleep status (good/poor). Primary endpoints were Bristol stool form scale (BSFS) score and correlations between sleep disorder criteria of the Pittsburgh Sleep Quality Index (PSQI) and sleep status (good/poor sleep). Secondary endpoints included correlations between quality of life (QOL) and mood, medical, lifestyle, and sleep factors. RESULTS: The proportion of participants with BSFS category 4 (normal stool) was significantly higher in the good sleep group (P < 0.001). Sleep disturbance (P < 0.05), sleep quality, and duration, use of hypnotic medication, and daytime dysfunction of PSQI (all P < 0.001) significantly correlated with poor sleep. In the poor sleep group, QOL was significantly worse and anxiety and depression levels were significantly higher (all P < 0.001) compared with the good sleep group. Anemia and smoking (both P < 0.05), recent body weight increases, and poor eating habits (all P < 0.001) were significantly higher in the poor sleep group. Male sex, onset associated with change in frequency of stools, sensation of incomplete evacuation for at least 25% of defecations, and manual maneuvers to facilitate at least 25% of defecations correlated with poor sleep. CONCLUSIONS: Subjects with constipation and poor sleep experienced severe symptoms and had poor QOL. These data support the need for a multifocal treatment approach, including lifestyle advice and pharmacotherapy.