The safety and effectiveness of naldemedine for opioid-induced constipation in patients with advanced cancer in real-world palliative care settings: a multicenter prospective observational study.

PURPOSE: In this study, we aimed to evaluate the safety and effectiveness of naldemedine for treating opioid-induced constipation (OIC) in patients with advanced cancer, who are receiving palliative care, and particularly explored its early effects. METHODS: Palliative care teams and inpatient palliative care units across 14 institutions in Japan were included in this multicenter, prospective, observational study. Patients who were newly prescribed a daily oral dose of 0.2 mg naldemedine were enrolled. The spontaneous bowel movement (SBM) within 24 h after the first dose of naldemedine was considered the primary outcome, whereas, the secondary outcomes included weekly changes in SBM frequency and adverse events. RESULTS: A total of 204 patients were enrolled and 184 completed the 7-day study. The average age of the participants (103 males, 101 females) was 63 ± 14 years. The primary cancer was detected in the lungs (23.5%), gastrointestinal tract (13.7%), and urological organs (9.3%). A considerable proportion of patients (34.8%) had ECOG performance status of 3-4. Most patients were undergoing active cancer treatment, however, 40.7% of the patients were receiving the best supportive care. Within 24 h of the first naldemedine dose, 146 patients (71.6%, 95% CI: 65.4-77.8%) experienced SBMs. The weekly SBM counts increased in 62.7% of the participants. The major adverse events included diarrhea and abdominal pain, detected in 17.6% and 5.4% of the patients, respectively. However, no serious adverse events were observed. CONCLUSION: Conclusively, naldemedine is effective and safe for OIC treatments in real-world palliative care settings. TRIAL REGISTRATION NUMBER: UMIN000031381, registered 20/02/2018.

Prevalence of osteochondritis dissecans of the capitellum in elementary school baseball players based on ultrasonographic screening: a 15-year overview in Tokushima, Japan.

Background: Although several operative procedures have evolved for capitellar osteochondritis dissecans (OCD), the best outcome is achieved by early detection and conservative treatment. The objective of this study was to clarify changes in the prevalence of capitellar OCD in young baseball players over a long-term period based on consistent criteria in Tokushima, Japan between 2006 and 2020. Methods: The number of players who underwent screening and the discovery rate of capitellar OCD during the study period were investigated. School grade and radiographic stage were also evaluated. Results: The confirmation rate was significantly higher when ultrasonographic screening was performed than when screening was based on physical findings (65.8% vs. 1.9%, P < .001). The overall incidence of OCD in elementary school players based on ultrasonographic screening was 1.4% during the 10-year study period. Twenty-one (10.8%) of the 195 players identified to have OCD had experienced lateral elbow pain. When classified radiographically, the lesion was stage I in 73.3% of cases, stage II in 24.1%, and stage III in 2.6%. No cases of OCD were diagnosed before the fourth grade. The prevalence rates increased gradually from the fourth grade to the sixth grade. Conclusion: Ultrasonographic screening could be more effective for detecting capitellar OCD than screening based on physical findings. The overall prevalence of OCD among elementary school players was 1.4% over 10 years. The prevalence rates increased gradually from the fourth grade onwards.

Strain-level detection of Fusobacterium nucleatum in colorectal cancer specimens by targeting the CRISPR-Cas region.

IMPORTANCE: Fusobacterium nucleatum is one of the predominant oral bacteria in humans. However, this bacterium is enriched in colorectal cancer (CRC) tissues and may be involved in CRC development. Our previous research suggested that F. nucleatum is present in CRC tissues originating from the oral cavity using a traditional strain-typing method [arbitrarily primed polymerase chain reaction (AP-PCR)]. First, using whole-genome sequencing, this study confirmed an exemplary similarity between the oral and tumoral strains derived from each patient with CRC. Second, we successfully developed a method to genotype this bacterium at the strain level, targeting the clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated system, which is hypervariable (defined as F. nucleatum-strain genotyping PCR). This method can identify F. nucleatum strains in cryopreserved samples and is significantly superior to traditional AP-PCR, which can only be performed on isolates. The new methods have great potential for application in etiological studies of F. nucleatum in CRC.

Preoperative Weight Loss Program for Hepatocellular Carcinoma Patients with High Body Mass Index in Hepatectomy.

BACKGROUND: This study aimed to investigate the usefulness of a weight-loss program (WLP) in patients with a high body mass index (BMI) prior to liver resection (Hx) for hepatocellular carcinoma (HCC). METHODS: Among 445 patients with HCC who underwent initial Hx between 2000 and 2020, 19 with a high BMI (≥25.0) were enrolled in our WLP since 2014. For calorie restriction, the amount of energy consumed was calculated as the standard body weight (SBW) kg × 20-25 kcal/day. Protein mass was calculated as SBW kg × 1.0-1.2 g/day to maintain skeletal muscle mass. Patients also performed both aerobic and resistance exercises. The before-and-after changes were compared, and the effect of WLP on the short- and long-term results was investigated. RESULTS: The average length of WLP was 21 days, and weight loss was successfully achieved in all patients. Body fat mass was reduced during the program, while skeletal muscle mass was maintained. WLP led to improvements in liver function and fibrotic markers, without tumor progression. There were no postoperative complications (≥Clavien-Dindo [CD] III). A retrospective comparison between with and without WLP using propensity score-matching analysis revealed that WLP group showed better NLR value, however, there were no significant differences in both short and long-term outcomes after Hx based on participation in the WLP. CONCLUSIONS: WLP with multidisciplinary intervention improved immune-nutrition status and liver function of obese patients. WLP had not affected both short and long-term outcomes after Hx.

Palliative care unit treatment and care for a terminal breast cancer patient with untreated obsessive-compulsive disorder.

OBJECTIVES: Although palliative care units treat patients with various comorbidities, there are no reports of patients with obsessive-compulsive disorder (OCD). METHODS: The treatment and care of a breast cancer patient with OCD are presented. RESULTS: A woman in her 40s was admitted to the palliative care unit for terminal breast cancer. She spent most of the day cleaning the bath and bed areas, ignoring efforts to restrain her actions by the staff. After being diagnosed with OCD, the above symptoms improved through the coordinated action of the staff and medication. SIGNIFICANCE OF RESULTS: This is the first report of the diagnosis and treatment of a patient with OCD in a palliative care unit. Early psychiatric diagnosis and subsequent staff response contributed to improvement in the patient's quality of life.

Multiancestry genomic and transcriptomic analysis of gastric cancer.

Gastric cancer is among the most common malignancies worldwide, characterized by geographical, epidemiological and histological heterogeneity. Here, we report an extensive, multiancestral landscape of driver events in gastric cancer, involving 1,335 cases. Seventy-seven significantly mutated genes (SMGs) were identified, including ARHGAP5 and TRIM49C. We also identified subtype-specific drivers, including PIGR and SOX9, which were enriched in the diffuse subtype of the disease. SMGs also varied according to Epstein-Barr virus infection status and ancestry. Non-protein-truncating CDH1 mutations, which are characterized by in-frame splicing alterations, targeted localized extracellular domains and uniquely occurred in sporadic diffuse-type cases. In patients with gastric cancer with East Asian ancestry, our data suggested a link between alcohol consumption or metabolism and the development of RHOA mutations. Moreover, mutations with potential roles in immune evasion were identified. Overall, these data provide comprehensive insights into the molecular landscape of gastric cancer across various subtypes and ancestries.

Impact of postoperative physical activity on the development of pneumonia in the subacute phase after esophagectomy in patients with esophageal cancer: A retrospective cohort study.

PURPOSE: Physical activity is important to improve recovery following surgery. This study investigated the impact of physical activity on the development of pneumonia after radical esophagectomy in patients with thoracic esophageal cancer in the subacute phase from postoperative day 11 to hospital discharge. METHODS: This retrospective cohort study included 83 patients who underwent radical esophagectomy for esophageal cancer between 2016 and 2022. Physical activity was measured using an activity tracker, and the average number of steps between postoperative days 8 and 10 was examined. The primary outcome was pneumonia (Clavien-Dindo classification 2 or higher) developing between postoperative day 11 and hospital discharge. We used the receiver operating characteristic (ROC) curve analysis to calculate the optimal cutoff value of physical activity that can predict the development of pneumonia and define low physical activity. We used logistic regression analysis to investigate the impact of low physical activity on postoperative pneumonia. RESULTS: Pneumonia developed in 10 patients (12.0%) during the observation period. The optimal cutoff value of physical activity for predicting pneumonia was 1494 steps per day (sensitivity: 60.0%, specificity: 89.0%, area under the curve: 0.743). In multivariate analysis, low physical activity was an independent predictor of incident pneumonia [odds ratio: 12.10, 95% confidence interval: 2.21-65.90, p = 0.004], with adjustment for age, gastric tube reconstruction route, and postoperative recurrent nerve palsy. CONCLUSIONS: Physical activity following radical esophagectomy in patients with thoracic esophageal cancer was an independent predictor of the development of pneumonia in the subacute phase after radical esophagectomy.

Between-day reliability and minimum detectable change of the Conventional Gait Model 2 and Plug-in Gait Model during running.

BACKGROUND: The Plug-in Gait model (PiG) is commonly used in 3D motion analysis but has limited reliability. Although an improved version of PiG has been developed, called the Conventional Gait Model 2 (CGM2), there is limited evidence on its between-day reliability for running. RESEARCH QUESTION: What is the between-day intraclass correlation coefficient (ICC3,k) and minimum detectable change (MDC) of lower limb kinematics and kinetics for CGM2 during running and does reliability differ between CGM2 and PiG. METHODS: Twenty-three healthy participants performed running at a comfortable speed in two identical test sessions at least 5 days apart. Lower limb kinematic and kinetic data in the three planes of motion were calculated using CGM2 and PiG. The ICC and MDC were calculated for the kinematic and kinetic parameters at initial contact and peak during the stance phase of running. RESULTS: CGM2 kinematics showed good-to-excellent reliability (ICC: 0.75-0.93), except for hip extension and ankle internal rotation, and less than 5° MDC (1.8°-4.9°) of the coronal and sagittal planes, except for hip extension. PiG showed poor-to-moderate reliability (ICC: -0.15 to 0.72) in the coronal and transverse planes and greater than 5° MDC (5.0°-21.8°), except for knee extension, adduction, and ankle dorsiflexion. CGM2 showed good-to-excellent reliability for peak kinetics (ICC: 0.75-0.97), except for hip internal rotation and knee extension. The ICC and MDC were higher for CGM2 than PiG, with significant differences in the coronal plane of the hip and knee joints and transverse plane of the hip joint in kinematics and in the sagittal and coronal plane of the hip and knee joints in kinetics. SIGNIFICANCE: The between-day reliability of CGM2 was mostly good to excellent for lower limb kinematics and kinetics during running. We believe that CGM2 can more accurately assess kinematic differences between the coronal and transverse planes than the PiG.

Characteristics of the stand-to-sit motion in healthy older women†:†Evaluation of sitting impact by measurement of ground reaction forces.

Objectives : The aims of this study were to examine the biomechanics of StandTS movements in older adults and to identify their optimal StandTS motion by measuring sitting impact forces. Methods : Healthy older women (n = 17) and healthy young women (n = 18) were asked to perform SitTS and StandTS motions at a natural speed using a chair. We measured the ground reaction forces from the participants' feet and the chair, the angle of the trunk and ankle, vertical velocity, and postural muscle activities using a force plate, motion analyzer, and electromyography, respectively. Results : Sitting impact force was significantly greater in the older women than in the young women during the StandTS motion. There was a significant difference between the trunk angle and the ankle angle during the StandTS motion and sitting impact force had a significant negative correlation with the ankle joint motion in the older women. Conclusions : The ankle joint strategy was characterized by body sway resembling a single-segment-inverted pendulum and suggests that this response is less developed in the older adult. These results indicate that the ankle joint strategy may be an important factor involved in the sitting impact force. J. Med. Invest. 69 : 278-286, August, 2022.

Leukotriene Receptor Antagonist Therapy for the Chemoprevention of Human Rectal Aberrant Crypt Foci: Nonrandomized, Open-Label, Controlled Trial.

Leukotriene receptor antagonists (LTRA) are widely used drugs for treating allergic asthma, and they have recently been suggested to have a suppressive effect on carcinogenesis and cancer cell proliferation. Aberrant crypt foci (ACF) are considered a reliable surrogate biomarker of colorectal cancer. This prospective study explored the chemopreventive effect of an LTRA on colonic ACF formation and the safety of the medicine in patients as a pilot trial leading to a colorectal cancer chemoprevention trial.This was a nonrandomized, open-label, controlled trial in patients with colorectal ACFs. The participants were allocated to LTRA or observation groups. Patients in the LTRA group received 10 mg of montelukast orally daily for 8 weeks. After the intervention, colonoscopy was performed to evaluate the changes in the number of ACFs.From November 2017 to March 2020, 40 patients were enrolled. The first 30 were assigned to the LTRA group, and the remaining 10 were assigned to the observation group. In the LTRA group, the mean change in the number of ACFs per patient at 8 weeks from baseline was -2.4 ± 2.2, while the mean change in the observation group was 0.4 ± 2.3 (P = 0.002). There were no severe adverse events.This is the first study to explore the effect of LTRAs against colorectal ACF formation in humans. LTRAs are potential candidates for chemoprevention in colorectal cancer. PREVENTION RELEVANCE: We conducted the first LTRA chemoprevention trial for human rectal ACFs, which is considered a surrogate marker of colorectal carcinogenesis. 8-week treatment with LTRA suppressed ACF formation and cell proliferation in colonic epithelium. LTRAs are possible candidates for chemoprevention in colorectal cancer. See related Spotlight, p. 637.

One-year follow-up ultrasonographic study of the subchondral bone surface of the distal femoral epiphysis in children aged 9-11 years.

The aim of this study was to investigate the subchondral bone surface of the distal femoral epiphysis and monitor the morphologic changes on ultrasonography (US) in growing children. A total of 160 football players aged 9-11 years underwent ultrasonographic examination of both knees. The regularity of the subchondral bone surface of the femoral condyles was classified as grade 0 (smooth), 1 (focal semilunar depression or indentation) or 2 (broad irregularity). The relationship between age and frequency of irregularity was analyzed. Children with a grade 2 were referred for radiography and MRI to check for osteochondritis dissecans (OCD). All players underwent repeat examination 1 year later. On initial examination, 82/320 knees (25.6%) were categorized as grade 0, 237/320 (74.1%) as grade 1 and 1 (0.3%) as grade 2. Logistic regression analysis revealed a significant association of increasing age with decreased irregularity of subchondral bone in the lateral and medial condyles (P = 0.019 and P < 0.001 for trend, respectively). One year later, logistic regression analysis showed that increasing age was significantly associated with decreased appearance of subchondral bone irregularity in the medial condyle (P = 0.005 for trend) and a greater likelihood of disappearance of irregularity in both condyles (P < 0.001 for trend). Of five knees classified as grade 2, four had evidence of OCD on radiography and MRI. Subchondral bone surface irregularity of the distal femoral epiphysis was more common on US in growing children aged 9-11 years, and transition from an irregular to a smooth outline accelerated after age 10 years. US is a reliable method for assessing the morphology of the distal femoral epiphysis and could be a useful screening tool for detecting OCD.

A prospective interventional trial on the effect of periodontal treatment on Fusobacterium nucleatum abundance in patients with colorectal tumours.

Fusobacterium nucleatum is associated with the progression of colorectal cancer. Thus, the possibility of preventing colorectal cancer or its progression by targeting F. nucleatum has been explored. As F. nucleatum is associated with periodontitis, we analysed whether treating periodontitis could influence F. nucleatum abundance in the colon. Patients with colorectal tumours who underwent colonoscopy were recruited. Patients diagnosed with periodontitis by a dentist were treated for approximately 3 months. Endoscopic resection of colorectal tumours was performed after periodontitis treatment, and resected tumours were pathologically classified as high-(HGD) or low-grade dysplasia (LGD). Saliva and stool samples were collected before and after the treatment. Of the 58 patients with colorectal tumours, 31 were included in the study, 16 showed improvement in periodontitis, and 11 showed no improvement. Stool F. nucleatum levels before treatment were significantly lower in the LGD group than in the HGD group. A significant decrease in faecal F. nucleatum levels was observed in patients who underwent successful treatment but not in those whose treatment failed. Salivary F. nucleatum levels were not altered in patients despite periodontal treatment. Thus, successful periodontitis treatment reduces stool F. nucleatum levels and may aid research on periodontitis and suppression of colorectal cancer development.

Single-cell DNA and RNA sequencing reveals the dynamics of intra-tumor heterogeneity in a colorectal cancer model.

BACKGROUND: Intra-tumor heterogeneity (ITH) encompasses cellular differences in tumors and is related to clinical outcomes such as drug resistance. However, little is known about the dynamics of ITH, owing to the lack of time-series analysis at the single-cell level. Mouse models that recapitulate cancer development are useful for controlled serial time sampling. RESULTS: We performed single-cell exome and transcriptome sequencing of 200 cells to investigate how ITH is generated in a mouse colorectal cancer model. In the model, a single normal intestinal cell is grown into organoids that mimic the intestinal crypt structure. Upon RNAi-mediated downregulation of a tumor suppressor gene APC, the transduced organoids were serially transplanted into mice to allow exposure to in vivo microenvironments, which play relevant roles in cancer development. The ITH of the transcriptome increased after the transplantation, while that of the exome decreased. Mutations generated during organoid culture did not greatly change at the bulk-cell level upon the transplantation. The RNA ITH increase was due to the emergence of new transcriptional subpopulations. In contrast to the initial cells expressing mesenchymal-marker genes, new subpopulations repressed these genes after the transplantation. Analyses of colorectal cancer data from The Cancer Genome Atlas revealed a high proportion of metastatic cases in human subjects with expression patterns similar to the new cell subpopulations in mouse. These results suggest that the birth of transcriptional subpopulations may be a key for adaptation to drastic micro-environmental changes when cancer cells have sufficient genetic alterations at later tumor stages. CONCLUSIONS: This study revealed an evolutionary dynamics of single-cell RNA and DNA heterogeneity in tumor progression, giving insights into the mesenchymal-epithelial transformation of tumor cells at metastasis in colorectal cancer.

Limiting the Pitch Count in Youth Baseball Pitchers Decreases Elbow Pain.

BACKGROUND: Reducing the number of pitches thrown is regarded as the most effective way to prevent throwing injuries in youth baseball pitchers. However, few studies have compared the effectiveness of limiting the pitch count versus the limiting the number of innings pitched in terms of elbow injuries. HYPOTHESIS: We hypothesized that, compared with inning limits, pitch count limits would lead to greater decreases in elbow pain, range of motion deficits, positive moving valgus stress test results, and the risk of capitellar osteochondritis dissecans (OCD). STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: This study retrospectively reviewed baseball pitchers aged 8 to 12 years in 2017 and 2018. Inning and pitch count limits in games were set to a daily maximum of 7 innings in 2017 and 70 pitches in 2018. Elbow pain, range of motion, and moving valgus stress test results were evaluated. The presence of capitellar OCD was assessed on ultrasonographic and radiographic images. RESULTS: A total of 352 pitchers in 2017 and 367 pitchers in 2018 participated. The mean pitch count per game was lower in the pitch count limit (CL) group (52.5 ± 16.0) than in the inning limit (IL) group (98.2 ± 19.5) (P < .001). Compared with the IL group, the CL group had significantly lower rates of elbow pain (40.9% vs 31.9%, respectively; P = .01) and reduced flexion (19.0% vs 10.6%, respectively; P = .001). Multivariate analysis revealed a significant association between elbow pain and age in both the IL and the CL groups (P < .0001 and P = .02, respectively) and between OCD and elbow pain in the CL group (P = .04). CONCLUSION: A pitch count limit of ≤70 pitches per day for baseball pitchers ≤12 years could be more protective against elbow pain and reduced flexion than a limit of ≤7 innings per day, but it may not be effective for reducing the risk of capitellar OCD.

Precision modeling of gall bladder cancer patients in mice based on orthotopic implantation of organoid-derived tumor buds.

Genetically engineered mice (GEM) are the gold standard for cancer modeling. However, strict recapitulation of stepwise carcinogenesis from a single tumor-initiating epithelial cell among genetically intact cells in adults is not feasible with the currently available techniques using GEM. In previous studies, we partially overcame this challenge by physically isolating organs from adult animals, followed by genetic engineering in organoids and subcutaneous inoculation in nude mice. Despite the establishment of suitable ex vivo carcinogenesis models for diverse tissues, tumor development remained ectopic and occurred under immunodeficient conditions. Further refinement was, therefore, necessary to establish ideal models. Given the poor prognosis and few models owing to the lack of gall bladder (GB)-specific Cre strain, we assumed that the development of authentic models would considerably benefit GB cancer research. Here, we established a novel model using GB organoids with mutant Kras and Trp53 loss generated in vitro by lentiviral Cre transduction and CRISPR/Cas9 gene editing, respectively. Organoid-derived subcutaneous tumor fragments were sutured to the outer surface of the GB in syngeneic mice, which developed orthotopic tumors that resembled human GB cancer in histological and transcriptional features. This model revealed the infiltration of similar subsets of immune cells in both subcutaneous and orthotopic tumors, confirming the appropriate immune environment during carcinogenesis. In addition, we accurately validated the in vivo efficacy of gemcitabine, a common therapeutic agent for GB cancer, in large cohorts. Taken together, this model may serve as a promising avatar of patients with GB cancer in drug discovery and precision medicine.

Efficacy of sedation with dexmedetomidine plus propofol during esophageal endoscopic submucosal dissection.

BACKGROUND AND AIM: During endoscopic submucosal dissection for superficial esophageal cancer, patient body movement can sometimes occur, which may cause discontinuation of the procedure. Propofol and dexmedetomidine have recently been found to be useful sedatives for endoscopic submucosal dissection. This study investigated whether sedation using propofol plus dexmedetomidine can suppress the patient's body movements during esophageal endoscopic submucosal dissection and compared this combination with sedation using propofol alone. METHODS: This was a prospective double-blind randomized controlled trial. Patients with superficial esophageal cancers who underwent esophageal endoscopic submucosal dissection at Yokohama City University Hospital were prospectively enrolled and were randomly assigned to the propofol and the propofol plus dexmedetomidine groups. The primary endpoint was the incidence of restlessness. The secondary endpoints were the satisfaction score, maintenance dose of propofol, and number of rescue propofol injections. RESULTS: Sixty-six patients (propofol group: n = 33; combination group: n = 33) were included. The combination group had a significantly lower incidence of restlessness than the propofol group (3.0% vs 27.3%, P = 0.02). In the combination group, the satisfaction scores of the endoscopists were significantly higher, the maintenance dose of propofol was significantly lower, and the number of rescue propofol injections was lower than those in the propofol group (3.0% vs 18.2%, P < 0.001). Although the incidence of bradycardia was significantly higher in the combination group (30.3% vs 3.0%, P < 0.01), no serious adverse effects occurred. CONCLUSION: The propofol plus dexmedetomidine combination provided excellent sedation that effectively suppressed the patient's body movements during esophageal endoscopic submucosal dissection.

Relationship between Stool Form and Quality of Life in Patients with Chronic Constipation: An Internet Questionnaire Survey.

INTRODUCTION: Chronic constipation (CC) is a highly prevalent functional bowel disorder with low treatment satisfaction and impaired quality of life (QOL). However, physicians tend to emphasize only "stool frequency," and relationship between "stool form" and QOL remains unclear. In this study, we aimed to investigate the actual situation of CC treatment in Japan and elucidate the relationship between stool form and QOL in patients with CC. METHODS: We conducted an online questionnaire survey in September 2018 targeting Japanese adult patients already diagnosed with CC and taking prescribed drugs. Assessments included the type of drug treatment, treatment duration, frequency of drug use, frequency of bowel movements (BMs), Bristol Stool Form Scale (BSFS), and Japanese version of the Patient Assessment of Constipation QOL (PAC-QOL) scores. Relationship between BSFS and Japanese PAC-QOL scores was analyzed, and most important factor that influences QOL was investigated. RESULTS: A total of 614 subjects were enrolled. Of these, 398 (64.8%) regularly used magnesium oxide and 162 (26.4%) used stimulant laxative, especially 81 (50.0%) used stimulant laxative "everyday." Mean score of the PAC-QOL was 1.29 ± 0.74, and the lowest score (highest QOL) of 0.94 ± 0.61 was observed in BSFS type 4. Significant difference was seen between BSFS type 4 and all the other types except type 7. Multivariate analysis revealed that normal stool form (BSFS type 4) and BMs ≥3/week are strongly related to decreases of PAC-COL score. In BSFS types 6 and 7, 36% of individuals experienced self-discontinuation of prescribed drugs and 53% self-reduced drug intake because of excessive effects. CONCLUSIONS: Stool form and frequency of BMs are relevant to QOL, especially normal stool form (BSFS type 4) is important for improving the QOL in patients with constipation. Physicians should focus on "stool form" and reconsider the prescription especially in BSFS types 6-7 patients.

Osteochondritis Dissecans of the Capitellum†:Review of the Literature.

Osteochondritis dissecans (OCD) of the capitellum is a leading cause of elbow disability in adolescent baseball players. Previous studies have not found an association of player position with capitellar OCD. Elbow pain and a longer playing history might be related to progression of capitellar OCD but do not in themselves increase the risk of development of the condition. The cause of capitellar OCD is likely to include a combination of repetitive microtrauma and internal factors, such as ischemia and genetic predisposition. A combination of radiography, computed tomography, magnetic resonance imaging, and ultrasonography have aided our understanding of the pathology of capitellar OCD. Screening using ultrasonography enables early detection and provides an opportunity for successful conservative treatment. Treatment has conventionally included both operative and nonoperative measures based on the stage and size of the lesion, skeletal maturity, subjective symptoms, and structural integrity of the cartilage. Early-stage lesions respond better to nonoperative treatment than those in more advanced stages. Operative indications include persistent symptoms despite nonoperative treatment, symptomatic loose bodies, and displacement or detachment of fragments. J. Med. Invest. 67 : 217-221, August, 2020.

The efficacy of aspirin and metformin combination therapy in patients with rectal aberrant crypt foci: a double-blinded randomized controlled trial.

BACKGROUND: The incidence and mortality rates of colorectal cancer (CRC) continue to increase worldwide. Therefore, new preventive strategies are needed to lower the burden of this disease. Previous studies reported that aspirin could suppress the development of sporadic colorectal adenoma. In addition, metformin is a biguanide derivative that is long widely used for the treatment of diabetes mellitus and has recently been suggested to have a suppressive effect on carcinogenesis and cancer cell growth. Both drugs exhibit a chemopreventive effect, but their efficacy is limited. Aberrant crypt foci (ACF), defined as lesions containing crypts that are larger in diameter and stain more darkly with methylene blue than normal crypts, are more prevalent in patients with cancer and adenomas, and considered a reliable surrogate biomarker of CRC. Thus, we designed a prospective trial as a preliminary study prior to a CRC chemoprevention trial to evaluate the chemopreventive effect of aspirin combined with metformin on colorectal ACF formation in patients scheduled for polypectomy. METHODS: This study is a double-blind randomized controlled trial that will be conducted in patients with both colorectal ACF and colorectal polyps scheduled for polypectomy. Eligible patients will be recruited for the study and the number of ACF in the rectum will be counted at the baseline colonoscopy. Then, the participants will be allocated to one of the following two groups; the aspirin plus placebo group or the aspirin plus metformin group. Patients in the aspirin plus placebo group will receive oral aspirin (100 mg) and placebo for 8 weeks, and those in the aspirin plus metformin group will receive oral aspirin (100 mg) and metformin (250 mg) for 8 weeks. After 8 weeks of administration, polypectomy will be performed to evaluate changes in the number of ACF, and the cell-proliferative activity in the normal colorectal mucosa and colorectal polyps. DISCUSSION: This is the first study proposed that will explore the effect of aspirin combined with metformin on the formation of colorectal ACF in humans. TRIAL REGISTRATION: This trial has been registered in the University Hospital Medical Information Network (UMIN) Clinical Trials Registry as UMIN000028259 . Registered 17 July 2017.

The efficacy of a leukotriene receptor antagonist in the treatment of human rectal aberrant crypt foci: a nonrandomized, open-label, controlled trial.

BACKGROUND: Leukotriene receptor antagonists (LTRAs) are broadly used for the management of allergic asthma and have recently been indicated to inhibit carcinogenesis and cancer cell growth. In colorectal cancer (CRC) chemoprevention studies, the occurrence of adenoma or CRC itself is generally set as the trial endpoint. Although the occurrence rate of CRC is the most confident endpoint, it is inappropriate for chemoprevention studies because CRC incidence rate is low in the general population and needed for long-term monitoring. Aberrant crypt foci (ACF), defined as lesions containing crypts that are larger in diameter and darker in methylene blue staining than normal crypts, are regarded to be a fine surrogate biomarker of CRC. Therefore, this prospective study was designed to explore the chemopreventive effect of LTRA on colonic ACF formation and the safety of the medicine in patients scheduled for a poly resection as a pilot trial leading the CRC chemoprevention trial. METHODS: This study is a nonrandomized, open-label, controlled trial in patients with colorectal ACF and polyps scheduled for a polypectomy. Participants meet the inclusion criteria will be recruited, and the number of ACF in the rectum will be counted at the baseline colonoscopic examination. Next, the participants will be assigned to the LTRA or no treatment group. Participants in the LTRA group will continue 10 mg of oral montelukast for 8 weeks, and those in the no treatment group will be observed without the administration of any additional drugs. At the end of the 8-week LTRA intervention period, a polypectomy will be conducted to evaluate the changes in the number of ACF, and cell proliferation in the normal colorectal epithelium will be analyzed. DISCUSSION: This will be the first study to investigate the effect of LTRAs on colorectal ACF formation in humans. TRIAL REGISTRATION: This trial has been registered in the University Hospital Medical Information Network (UMIN) Clinical Trials Registry as UMIN000029926 . Registered 10 November 2017.