Background and aims: Corticotropin releasing hormone (CRH) is a major mediator of the stress response in the brain-gut axis. Irritable bowel syndrome (IBS) is presumed to be a disorder of the brain-gut link associated with an exaggerated response to stress. We hypothesised that peripheral administration of a-helical CRH (ahCRH), a non-selective CRH receptor antagonist, would improve gastrointestinal motility, visceral perception, and negative mood in response to gut stimulation in IBS patients. Methods: Ten normal healthy subjects and 10 IBS patients, diagnosed according to the Rome II criteria, were studied. The tone of the descending colon and intraluminal pressure of the sigmoid colon were measured at baseline, during rectal electrical stimulation (ES), and at recovery after administration of saline. Visceral perception after colonic distension or rectal ES was evaluated as threshold values on an ordinate scale. The same measurements were repeated after administration of ahCRH (10 mg/kg). Results: ES induced significantly higher motility indices of the colon in IBS patients compared with controls. This response was significantly suppressed in IBS patients but not in controls after administration of ahCRH. Administration of ahCRH induced a significant increase in the barostat bag volume of controls but not in that of IBS patients. ahCRH significantly reduced the ordinate scale of abdominal pain and anxiety evoked by ES in IBS patients. Plasma adrenocorticotropic hormone and serum cortisol levels were generally not suppressed by ahCRH. Conclusion: Peripheral administration of ahCRH improves gastrointestinal motility, visceral perception, and negative mood in response to gut stimulation, without affecting the hypothalamo-pituitary-adrenal axis in IBS patients.

New strategies for the care of irritable bowel syndrome (IBS) are developing and several novel treatments have been globally produced. New methods of care should be customized geographically because each country has a specific medical system, life style, eating habit, gut microbiota, genes and so on. Several clinical guidelines for IBS have been proposed and the Japanese Society of Gastroenterology (JSGE) subsequently developed evidence-based clinical practice guidelines for IBS. Sixty-two clinical questions (CQs) comprising 1 definition, 6 epidemiology, 6 pathophysiology, 10 diagnosis, 30 treatment, 4 prognosis, and 5 complications were proposed and statements were made to answer to CQs. A diagnosis algorithm and a three-step treatment was provided for patients with chronic abdominal pain or abdominal discomfort and/or abnormal bowel movement. If more than one alarm symptom/sign, risk factor and/or routine examination is positive, colonoscopy is indicated. If all of them, or the subsequent colonoscopy, are/is negative, Rome III or compatible criteria is applied. After IBS diagnosis, step 1 therapy consisting of diet therapy, behavioral modification and guttargeted pharmacotherapy is indicated for four weeks. Nonresponders to step 1 therapy proceed to the second step that includes psychopharmacological agents and simple psychotherapy for four weeks. In the third step, for patients nonresponsive to step 2 therapy, a combination of gut-targeted pharmacotherapy, psychopharmacological treatments and/or specific psychotherapy is/are indicated. Clinical guidelines and consensus for IBS treatment in Japan are well suited for Japanese IBS patients; as such, they may provide useful insight for IBS treatment in other countries around the world.

The DESTINY-Breast04 clinical trial is currently investigating whether trastuzumab deruxtecan (T-DXd) is effective in HER2-low as well as HER2-positive breast cancer. This highlights the interest in treatment strategies for patients with HER2-low breast cancer. The current study was therefore designed to determine the frequency of HER2-low among all breast cancers, and to compare the prognosis of HER2low patients with that of HER2-negative patients. MethodsWe retrospectively reviewed the biological data from 4,918 of 4,977 primary breast cancer patients who attended our institute. We quanti ed the overall frequency of breast cancer patients with a new HER2-low subtype that was de ned by an immunohistochemistry score of IHC1+ or IHC2+/ISH-. We then compared the clinical characteristics and prognosis of HER2-low patients with that of patients who did not have HER2 ampli cation (HER2-0). ResultsLow HER2 expression was found in 3169 (64.4%) patients; 2860 (58.1%) were HR-positive and 309(6.3%) were HR-negative. Among HER2-0 patients, 681(13.9%) were HR-positive and 157(3.2%) were HRnegative. The HER2-0 group tended to have more poor prognostic factors than the HER2-low group, irrespective of HR status. There were no statistically signi cant differences between the prognosis of HER2-low and HER2-0 patients, regardless of HR status. However, patients in the HER2-low group tended to have better prognosis than those in the HER2-0 group. ConclusionHER2-low patients did not have a signi cantly different prognosis than HER2-0 patients, regardless of HR status. However, we should consider tailoring therapies for patients with HRE2-low early breast cancer according to their HR status.

Little is known about the prevalence and risk factors for development of irritable bowel syndrome (IBS) in Japan. In the United States, it is reported that heredity and social learning contribute to the development of IBS. Our aims were (1) to estimate the prevalence of IBS, (2) to confirm that subjects with IBS are more likely to have parents with a history of bowel problems, (3) to confirm that gastroenteritis is a risk factor for IBS, and (4) to determine whether these two risk factors interact with psychological distress. Prevalence was estimated from a sample of 417 young adults seen for annual health screening examinations. To evaluate risk factors related to consulting physicians, the 46 subjects who fulfilled Rome II diagnostic criteria for IBS but denied ever having seen a physician about these symptoms (IBS non-consulters) were compared to the 317 subjects who did not meet the criteria for IBS (controls) and to a group of 56 patients diagnosed with IBS by gastroenterologists (IBS patients). All subjects completed the Gastrointestinal Symptoms Rating Scale, the State-Trait Anxiety Inventory, the Self-Rating Depression Scale, the Perceived Stress Scale, and the SF-36 quality of life scale. Fourteen and two-tenths percent (15.5% of females and 12.9% of males) of the community sample met the criteria for IBS diagnosis, of whom 22% consulted physicians. IBS patients and IBS nonconsulters were more likely than controls to have a parental history (33.9 vs. 12.6%, P < 0.001, for patients and 26.1 vs. 12.6%, P < 0.01, for nonconsulters) and were more likely to report an infective history compared to controls (44.6 vs. 16.1%, P < 0.001, for patients and 32.6 vs. 16.1%, P < 0.01, for nonconsulters). Two-way analysis of variance showed that the parental history was associated with a significantly greater impact on symptoms of indigestion, diarrhea, constipation, state and trait anxiety, and the SF-36 scales for social functioning and role emotional and that an infective history was associated with a greater impact on bodily pain. Both a parental history of bowel problems and a history of acute gastroenteritis are significant risk factors for development of IBS in Japan, as reported for the United States. Moreover, patients with such a family history show more psychological distress than other patients.

Aims: To compare quality of life (QOL) for patients with irritable bowel syndrome (IBS) between the U.S. and Japan, it is indispensable to develop common instruments. The IBS-QOL, which is widely used in Western countries, was translated into Japanese as there has been a lack of Japanese disease-specific QOL measures for IBS. Methods:The original 34 items of the IBS-QOL were translated from English into Japanese through two independent forward translations, resolution, back translation, and resolution of differences. Forty nine patients who had GI symptoms but did not have any organic diseases (including 30 IBS patients diagnosed by Rome II criteria) were recruited from Tohoku University Hospital in Sendai, Japan and completed a Japanese version of the IBS-QOL (IBS-QOL-J) concomitant with a Japanese version of the IBS severity index (IBSSI-J) twice within 7-14 days. Results:The IBS-QOL-J demonstrated high internal consistency (Cronbach's alpha; 0.96) and high reproducibility (intraclass correlation coefficient; 0.92, p < 0.001). Convergent analyses confirmed that the overall score of IBS-QOL-J was significantly correlated with overall severity of IBS symptoms on the IBSSI-J (r = -0.36, p = 0.01) and with the individual items on the IBSSI-J that assess interference with life in general (r = -0.47, p = 0.001) and dissatisfaction with bowel habits (r = -0.32, p < 0.05). Eight patients who reported continuous abdominal pain in the past 6 months had significantly lower scores in the IBS-QOL-J than those who did not (53.7 +-12.7 vs. 73.6 +-19.5, p < 0.01). Age, sex, education or marital status did not affect scores on the measure. Conclusion:The IBS-QOL-J is a reliable instrument to assess the disease-specific QOL for IBS. Considering cross-cultural comparison, this measure is likely to be a valuable tool to investigate the QOL in Japanese patients with IBS.

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The RIIMQ-J and IBSSI-J are valid, reliable, and appropriate instruments for detecting and assessing the severity of IBS status in Japanese patients.

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