KEIO JOURNAL OF MEDICINE最新文献

Finding cures is the ultimate goal of research on autoimmune diseases. Pemphigus is an autoantibody-mediated autoimmune skin disease in which specific autoantibodies target desmogleins 1 and 3 as autoantigens. The condition leads to painful blisters and erosions in the skin and oral mucosa, impacting patients' ability to eat and other daily activities, significantly affecting quality of life. The molecular mechanisms by which these pathogenic autoantibodies induce blisters have been extensively studied and understanding has advanced considerably. However, many critical questions remain, such as the exact cause of the disease, the mechanisms that normally prevent autoimmunity, and the pathogenic cells involved, other than autoantibodies. This article focuses on the role of autoreactive T cells in pemphigus and uses the pemphigus model to answer some of these questions. Research into pemphigus has enhanced our understanding of both the pathogenic and regulatory mechanisms involved, not only in pemphigus but also in other skin diseases caused by cellular autoimmunity. The growing body of scientific evidence on pemphigus has made it a model disease, paving the way for the development of novel therapeutic approaches, including antigen-specific immunotherapy for autoimmune diseases and chronic inflammatory disorders.

The aim of this study was to identify ¹⁸F-fluorodeoxyglucose positron emission tomography/computed tomography (¹⁸F-FDG-PET/CT) parameters that could predict the prognosis of patients with esophageal cancer before and after undergoing chemoradiation therapy. We retrospectively reconstructed images under the same conditions for patients who underwent pre- and post-treatment ¹⁸F-FDG-PET for chemoradiation therapy for esophageal cancer. Correlations between 2-year survival rates and pre-treatment values, differences between pre- and post-treatment quotients, and their ratios were examined for various standardized uptake values (SUV), metabolic tumor volumes (MTV), and each SUVmean (Mean SUV)*MTV (Vol.mean). We enrolled 29 patients who underwent pre-and post-treatment ¹⁸F-FDG-PET. The median overall survival was 21.4 months (range, 3.6-100.9 months). Pre-treatment MTV had the most favorable hazard ratio (HR) for survival. However, the MTV product (Vol.meanQ), SUV corrected for basal metabolic rate using Mifflin-St Jeor estimation (BMR.ms), Vol.mean (SUVmeanQ) using the qPET method, SUVmean, and HR using Vol.meanQ corrected for body weight were nearly equivalent. No significant results were obtained for the pre- and post-treatment quotients. The pre- and post-treatment Vol.meanQ is a useful prognostic parameter that considers the effect of age-related loss of lean body mass. The use of parameters, including metabolism, will facilitate more appropriate use of ¹⁸F-FDG-PET before and after chemoradiation therapy.

It is desirable for community pharmacists to be involved in promoting and maintaining the oral health of local residents. In this study, we conducted a questionnaire survey of Japanese community pharmacists to understand the actual conditions and the attitudes of these pharmacists regarding oral healthcare advice. A web-based anonymous self-administered questionnaire survey was completed by community pharmacists from March 26 to 29, 2021. We received responses from 324 pharmacists. A majority of respondents (66.0%) regarded dealing with "daily oral health issues and oral care" as a role of community pharmacists. Respondents also reported being consulted by patients or customers about mouth ulcers (70.1%) and xerostomia (54.6%). However, the frequency of consumer inquiries about these oral conditions was less than once per week. Just over half of the respondents (52.2%) said they were confident about dealing with mouth ulcers, whereas less than 40% were confident about handling other oral problems. The most common anxiety was a "lack of knowledge about appropriate responses to oral symptoms" (60.2%). The respondents desired education and training (75.6%) to better promote oral health-related activities. Japanese community pharmacists believe that they have a role to play in oral health issues and oral care, but their level of confidence in their ability to respond to oral health issues is low. Pharmacists are concerned about their lack of knowledge about oral healthcare and they desire more opportunities for education and training so that they can perform pharmacy-based maintenance and promotion of oral healthcare for local residents.

A 0.04% mitomycin C (MMC) ophthalmic solution is not commercially available and is prepared in hospitals as required. The physical properties and stability of the MMC ophthalmic solution have not been clarified because of a lack of data. This study aimed to assess the stability of the MMC ophthalmic solution under various storage conditions. The MMC ophthalmic solution was prepared by dissolving 2 mg of MMC in 5 mL of saline solution. Each batch of ophthalmic solution was stored under three conditions [cold/shaded light, room temperature/shaded light, and room temperature/scattered light (approximately 4000 lx)], and MMC concentration was determined using high-performance liquid chromatography on days 0, 1, 3, 5, 7, 14, and 21. The expiry date was calculated based on the results of the degradation analysis. pH measurements and bacterial culture tests were conducted for each storage condition. The MMC concentrations on day 21 under cold/shaded light, room temperature/shaded light, and room temperature/scattered light were 340, 287, and 227 µg/mL, respectively. MMC concentrations decreased over time, and the decrease was highest when the samples were stored at room temperature and exposed to light, and lowest under cold conditions and protected from light. The pH of MMC solutions was 5.8 after preparation, which increased to 6.9 with time under all storage conditions. Culture tests did not detect any bacteria under any storage conditions. The MMC ophthalmic solution was most stable under cold/shaded conditions, and our study clarifies its expiry date for clinical use.

Digital therapeutics (DTx) have demonstrated promising potential as a novel therapeutic approach, with their clinical development gaining momentum. Comparison of DTx development between Japan, a relative newcomer, and Germany and the U.S., known for favorable circumstances, is a topic of interest. DTx developed in Japan as of November 2023 were identified on the Pharmaceuticals and Medical Devices Agency (PMDA) website and in the literature. Similar DTx available in the U.S. and Germany were identified in the databases maintained by the U.S. Food and Drug Administration (USFDA) and Federal Institute for Drugs and Medical Devices (BfArM). Data on their clinical trials and regulatory status were obtained from these databases and their respective national clinical trial registries. The data obtained were compared and analyzed. By November 2023, Japan had developed DTx, encompassing 11 therapeutic areas. Seven DTx had reached or completed the confirmatory study stage, whereas five DTx were in the exploratory phase. Twenty DTx in the therapeutic areas were selected from the U.S. and Germany. A total of 27 DTx were reviewed regarding the designs of confirmatory studies and regulatory actions taken. Trial designs demonstrated more similarities than differences across the countries and therapeutic areas. Placebo trial design-associated difficulties were conspicuous. Although regulatory actions to place DTx in the market differed across countries, they effectively ensured the efficacy and safety of DTx that were suitable for marketing considering the most current science. The regulatory measures in the three countries seem to have positively impacted DTx development.

Colorectal large villous adenomas are sometimes associated with McKittrick-Wheelock syndrome, a condition characterized by severe diarrhea leading to dehydration, electrolyte depletion, and acute renal failure, which can be life-threatening in some cases. The efficacy of radiotherapy for colorectal villous adenoma has rarely been reported. We present a rare case of McKittrick-Wheelock syndrome in an older man caused by a large colorectal villous adenoma. This case is notable because palliative external beam radiotherapy of 30 Gy in 10 fractions not only reduced the tumor size but also resulted in significant symptom relief. This report demonstrates the efficacy of palliative radiotherapy for severe colorectal villous adenomas as a valid treatment option, particularly in older patients with complications.

The incidence of breast cancer in patients with pre-existing interstitial lung disease has been rarely reported. Consequently, evidence supporting the safety of chemotherapy in this population remains limited. This report describes the case of a 55-year-old woman with a history of cryptogenic organizing pneumonia who received adjuvant chemotherapy for the management of breast cancer. The chemotherapy regimen comprised the administration of epirubicin/cyclophosphamide followed by the weekly administration of paclitaxel. This regimen was selected based on the findings of previous studies that assessed the utility of chemotherapy regimens for the treatment of lung cancer in patients with interstitial lung disease. Chemotherapy was completed without worsening of the cryptogenic organizing pneumonia or the appearance of new abnormal lung fields. Therefore, the administration of epirubicin/cyclophosphamide followed by the weekly administration of paclitaxel may be safe in patients with pre-existing interstitial lung disease. This regimen may be a suitable choice for the perioperative management of this population.

Hereditary breast and ovarian cancer syndrome (HBOC) is a hereditary tumor syndrome caused by mutations in BRCA genes. Advances in genetic testing technologies have enabled surveillance and risk-reducing surgeries for carriers of BRCA mutations, allowing for the early detection and prevention of cancer. However, the research and support infrastructure for addressing the psychological and social impacts of genetic diagnostics remain insufficient, and there is a need for mental and psychological support based on the needs of patients and their families. Here, we provide an overview of mindfulness, a psychotherapy that has been demonstrated to be effective in alleviating psychological distress in cancer patients, and we discuss the prospects for mindfulness therapy in HBOC patients.

In Japan, the rising incidence of hereditary breast and ovarian cancer syndrome (HBOC) follows partial insurance coverage introduced in 2020. Compared with the general population (~11% lifetime risk), individuals with HBOC face a significantly higher lifetime risk of breast cancer (48%-76%), often presenting at younger ages. BRCA1 mutations are linked to triple-negative breast cancer, whereas BRCA2 mutations typically result in luminal-type disease. Key risk management strategies include surveillance and prophylactic surgery. Annual magnetic resonance imaging and mammography are recommended at younger ages than in the general population, despite concerns regarding contrast agents, radiation exposure, and examination-related burdens. Although risk-reducing mastectomy lowers breast cancer risk by over 90%, it remains underutilized because of cosmetic and psychological considerations. Nipple-sparing or skin-sparing mastectomy combined with immediate or delayed reconstruction offers a balance between risk reduction and postoperative outcomes, although safety and procedure details still warrant careful evaluation. Managing the high breast cancer risk associated with HBOC requires ongoing efforts to refine current strategies while minimizing patient burden.

A program of recruiting families with hereditary pancreatic cancer and hereditary breast and ovarian cancer (HBOC) syndrome as high-risk individuals for pancreatic cancer surveillance using magnetic resonance cholangiopancreatography (MRCP) and endoscopic ultrasound (EUS) has proven effective, resulting in the improvement of early detection rates and life expectancy. Given this, recent guidelines recommend pancreatic surveillance for patients with familial pancreatic cancer and pathological variants of ten genes, including BRCA1/2. In April 2021, our hospital established the HBOC Center, which is operated by nine departments, including obstetrics and gynecology, breast surgery, pancreatology, urology, medical genetics, dermatology, psychiatry and neurology, and oncology. Currently, MRCP or EUS is performed once or twice a year in 63 cases with pathogenic variants in 54 families. Although 4 cases (6.3%) revealed pancreatic microcysts or branched intraductal papillary mucinous neoplasms, no sign of pancreatic cancer was detected. Since January 2021, the germline BRCA1/2 test for companion diagnosis of pancreatic cancer has been covered by insurance, improving the accessibility of genetic testing among patients with pancreatic cancer. However, the BRCA1/2 positivity rate remains low at 1.3%, and its indication for use is very limited. The implementation of genetic testing, including BRCA1/2 analysis, is necessary for the prevention and early detection of pancreatic cancer in high-risk families.