Lowering effect of combined sweet potato and onion intake on plasma quercetin concentration and underlying mechanism involving intestinal ß-glucosidase activity.

A combined intake of cooked sweet potato and fried onion in humans was found to suppress the increase of plasma quercetin metabolite concentration. Experiments using rat ß-glucosidase indicated that excess carbohydrate digestion products, especially glucose-containing saccharides, interfere with the deglycosylation of quercetin glucosides during intestinal epithelial uptake. Combined meals of sweet potato and onion may lower the bioavailability of onion quercetin glucosides.

Axillary lymphangioma that developed following COVID-19 vaccination: a case report.

BACKGROUND: Extensive vaccination programs are being implemented worldwide for coronavirus disease 2019 (COVID-19). With the spread of vaccination, swelling of the lymph nodes after vaccination is frequently seen. We encountered a patient who developed left axillary lymphadenoma following vaccine administration. CASE PRESENTATION: The patient was a Japanese woman in her 80 s who had previously undergone surgery for right breast cancer. She received two injections of the Pfizer-BioNTech COVID-19 vaccine in her left arm. Approximately 3 months later, she complained of left axillary swelling, and imaging resulted in a diagnosis of left axillary lymphangioma. In accordance with the patient's wishes, we performed axillary mass resection. The pathological diagnosis was lymphangioma. CONCLUSION: Our examination findings indicated that congestion of the axillary lymph vessels might have been caused by upper-arm injections of the COVID-19 vaccine.

Household Secondary Transmission of the Severe Acute Respiratory Syndrome Coronavirus 2 Alpha Variant From a Community Cluster in a Nursery in Japan.

BACKGROUND: Spread of variants of concerns (VOCs) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to an increase in children with coronavirus disease 2019 (COVID-19). In February 2021, clusters of the Alpha variant of SARS-CoV-2 started to be reported in Niigata, Japan, including a large nursery cluster. We investigated the transmission routes and household secondary attack rates (SARs) in this cluster. METHODS: Epidemiologic data related to a nursery cluster in Niigata, Japan, particularly child-origin and adult-origin SARs, were analyzed. VOCs were confirmed by whole-genome sequencing of virus from patients. RESULTS: In total, 42 persons (22 children and 20 adults) in the cluster were infected with the Alpha variant. In the nursery, 13 of 81 children (16.0%) and 4 of 24 teachers (16.7%) were infected. SARS-CoV-2 later spread to 25 persons (10 children and 15 adults) outside the nursery. Child-origin and adult-origin household SARs were 27.7% (13/47) and 47.0% (8/17) ( P = 0.11), respectively, which were higher than rates attributable to non-VOCs in previous studies. CONCLUSIONS: As compared with non-VOCs, the Alpha variant of SARS-CoV-2 exhibited high transmissibility among children and adults and may pose a high risk for household secondary transmission from SARS-CoV-2-infected children. Increased transmissibility of current or future VOCs could lead to greater transmission from children to adults or other children.

False-negatives due to poor specimens can be prevented based on the macroscopic findings for breast Vacuum-Assisted Biopsy specimens.

PURPOSE: Ultrasound-guided breast tissue biopsy is an essential technique for diagnosing breast disease, but sample errors reduce its accuracy. This study investigated whether the histopathological results can be inferred from the macroscopic findings for Ultrasound-guided breast Vacuum Assisted Biopsy (VAB) specimens. METHODS: Biopsy specimens from 101 patients who underwent mammary gland VAB were photographed with a smartphone, and the relationships between the macroscopic findings and the pathological results were examined. RESULTS: A significant difference was observed with regard to the presence/absence of turbidity: malignancy was detected in 33/37 (89%) specimens with turbidity and in 2/47 (4%) cases without turbidity (p<0.001). A significant difference was also observed regarding the surface properties:malignancy was detected in 14/70 (19%) smooth specimens and in 24/29 (83%) rough specimens (p<0.001). Also, malignancy was detected in 11/13 (85%) specimens with white spots, and the difference was significant (p<0.001). In addition, the characteristics of intraductal papilloma, fibroadenoma, and mastopathy could be confirmed by macroscopic findings. CONCLUSIONS: When needle-biopsy of a lesion that is targeted for resection yields macroscopic findings that match the predicted histopathological findings, it can be thought that the biopsy had been properly performed. This means that false-negatives due to poor specimens can be prevented. J. Med. Invest. 69 : 51-56, February, 2022.

Coronavirus Disease 2019 Cluster Originating in a Primary School Teachers' Room in Japan.

BACKGROUND: School closures are a subject of debate during the present coronavirus disease 2019 (COVID-19) pandemic. Because children are not the main driver of COVID-19 transmission in the community, school education must be prioritized in conjunction with appropriate infection prevention and control measures, as determined by local COVID-19 incidence. METHODS: We investigated the causes and transmission routes of a primary school cluster of COVID-19 that occurred during November and December 2020 in Niigata, Japan. RESULTS: In the cluster, the virus spread among teachers, then from teachers to students, and then to their family members. This primary school cluster comprised 26 infected patients and included teachers (13/33, 39%), students (9/211, 4%), and family members (4/65, 6%). The secondary attack rate from the 3 index teachers to the remaining 30 teachers was 33%; however, the rate to students was only 4%. Factors contributing to cluster formation include the fact that 2 of the index teachers continued working while symptomatic and that the environment and infection prevention measures in the teachers' room were inadequate. CONCLUSIONS: To open schools safely and without interruption, adequate measures to prevent COVID-19 infection in schools should be emphasized not only for children but also for teachers and their environment.

The use of platelet-rich fibrin with platelet-rich plasma support meniscal repair surgery.

INTRODUCTION: Platelet-rich fibrin (PRF) is the only autologous blood product that releases growth factors and has scaffolding properties. We hypothesized that the use of PRF and Platelet-rich plasma (PRP) would improve operative results, including the recovery of function and repaired meniscus. MATERIALS AND METHODS: Seventeen patients underwent arthroscopic meniscus repair with PRF and PRP (PRF group) using our novel device for the injection of the PRF into the joint. Another five patients as a control group underwent meniscal repair without PRF and PRP (non-PRF group). The groups were compared in terms of clinical results (Tegner Activity Level Scale, Lysholm Knee Scoring Scale, and International Knee Documentation Committee [IKDC] scores) and changes in magnetic resonance imaging (MRI) findings before surgery and 6 months after surgery. RESULTS: The Lysholm and IKDC scores improved in all patients postoperatively. However, there was no significant differencies in the postoperative score between the PRF group and the non-PRF group. Follow-up MRI findings did not clearly show improvements. CONCLUSIONS: PRF and PRP are autologous, safe, and cost-effective sources of growth factors. Therefore, we propose a new application of PRF and PRP for autologous transplantation in meniscus repair surgery.

Thirty percent of ductal carcinoma in situ of the breast in Japan is extremely low-grade ER(+)/HER2(-) type without comedo necrosis.

Background Overdiagnosis in mammography (MMG) is a problem. Combination of MMG and ultrasonography for breast cancer screening may increase overdiagnosis. Most cases of overdiagnosis are low-grade ductal carcinoma in situ (LGD), but no reports have focused on them. Materials and methods We immunostained 169 ductal carcinoma in situ (DCIS) cases for ER, PgR, HER2 and Ki67 and classified them into 4 subtypes: ER(+)/HER2(-), ER(+)/HER2(+), ER(-)/HER2(-) and ER(-)/HER2(+). The Ki67 index was used to evaluate the grade of malignancy and examined for correlations with each ER/HER2 subtype and the nuclear grade (NG), with/without comedo necrosis. Results The Ki67 index correlated significantly with NG, both with/without comedo necrosis, and reliably evaluated the grade of malignancy. The index for ER(+)/HER2(-) (n=117, 69.2%) was 7.45±7.10, which was significantly lower than for each of the other types. The index was 5.71±6.94 for ER(+)/HER2(-) without comedo necrosis (n=52, 30.8%), which was significantly lower than with comedo necrosis. This was considered LGD, characterized by absence of microcalcification in MMG and either presence of a solid mass or cystic lesion or absence of hypoechoic areas in ultrasound. Conclusion In Japan, ER(+)/HER2(-) without comedo necrosis accounts for about 30% of DCIS and is LGD. This may be being overdiagnosed. J. Med. Invest. 63: 192-198, August, 2016.

Assay of serum E2 concentration in postmenopausal breast cancer patients using a high-sensitivity RIA method is generally useful.

BACKGROUND: Serum E2 must be monitored for aromatase inhibitor (AI) therapy, but conventional assays lack sensitivity. SUBJECTS/METHODS: Forty amenorrheic breast cancer patients scheduled for AI treatment but requiring hormonological confirmation of their menopausal status were studied. Serum E2 data generated by high-sensitivity RIA and by LC-MS/MS were analyzed for correlation. RESULTS: RIA gave a higher E2 value than LC-MS/MS in 62% of cases, but there was a significant positive correlation. Patients whose E2 levels by RIA were ≥ 2.5 pg/mL higher than those by LC-MS/MS (RIA-H group) and all other patients (RIA-N group) were compared. Both groups showed strong correlations between the two assay methods. With both methods patients with a high BMI had significantly elevated E2. Multiple regression analysis used age, age at menarche, number of births and BMI as explanatory variables. Significant variables were the BMI with LC-MS/MS, and both BMI and age with RIA. The RIA-H and RIA-N groups showed no difference in regard to the BMI, whereas the age was significantly lower in the RIA-H group. SUMMARY: Serum E2 levels determined for postmenopausal women by RIA and LC-MS/MS generally correlated well. High-sensitivity RIA is a potentially useful clinical assay, but it overestimated serum E2 in some women. J. Med. Invest. 63: 236-240, August, 2016.

Among triple-negative breast cancers, HER2(0) breast cancer shows a strong tendency to be basal-like compared with HER2(1+) breast cancer: preliminary results.

BACKGROUND: Diagnosis of triple-negative breast cancer (ER-negative, PgR-negative, HER2-negative; TNBC) is performed by means of immunohistological staining. HER2-negative includes HER2(0) and HER2(1+), based on differences in the staining intensity, but there have been no reports on comparison of these two types in TNBC. Accordingly, this study was designed to investigate the possible differences in the biological characteristics of HER2(0) breast cancer and HER2(1+) breast cancer in TNBC. METHODS: Tissue specimens from 89 TNBC patients were immunohistochemically stained for CK5/6, EGFR, p53, Ki67, E-cadherin, TOP2A and Bcl-2. The expressions of these markers and the clinicopathological findings were compared between the HER2(0) patient group and the HER2(1+) patient group. When either CK5/6 or EGFR was positive, the specimen was judged to be the basal-like phenotype of breast cancer. RESULTS: The percentages of CK5/6- and/or EGFR-positive specimens in the HER2(0) and HER2(1+) groups were 44.9 and 16.8%, respectively, showing that there was a significantly greater number of basal-like phenotype patients in the HER2(0) group (p < 0.01). The percentage of E-cadherin-positive specimens in the HER2(0) group was 66.6%, which was significantly greater than the 40.0% recorded in the HER2(1+) group (p < 0.05). The respective percentages of TOP2A-positive specimens in the HER2(0) and HER2(1+) groups were 55.0 and 30.0%, and the difference was statistically significant (p < 0.05). CONCLUSION: In TNBC, HER2(0) breast cancer showed a strong tendency to include more of the basal-like phenotype compared with HER2(1+) breast cancer. The staining results indicated the possibility that HER2(0) breast cancer and HER2(1+) breast cancer have different characteristics.

The time since last menstrual period is important as a clinical predictor for non-steroidal aromatase inhibitor-related arthralgia.

BACKGROUND: The clinical predictors of aromatase inhibitor-related arthralgia (AIA), a drug-related adverse reaction of aromatase inhibitors (AIs), remain unclear. METHODS: AIA was prospectively surveyed every 4 months in 328 postmenopausal breast cancer patients administered a non-steroidal AI (anastrozole). Various clinicopathological parameters were recorded and analyzed (chi-square test, Fisher's exact test and logistic regression analysis). RESULTS: The mean observation period was 39.9 months. AIA manifested in 114 patients (34.8%), with peaks of onset at 4 (33.7%) and 8 months (11.4%) after starting AI administration. Some cases manifested even after 13 months. AIA tended to occur in younger patients (incidences of 46.3%, 37.4% and 28.0% for ages of < 55, 55-65 and > 65 years, respectively (p = 0.063)) and decreased significantly with the age at menarche (53.3%, 35.3% and 15.4% for < 12, 12-15 and > 15 years, respectively (p = 0.036)). The incidences were 45.1%, 46.3 and 25.1% for the time since the last menstrual period (LMP) < 5 years, 5-10 years and > 10 years, being significantly lower at > 10 years (p < 0.001). In logistic regression analysis, the AIA incidence was significantly lower in the time since LMP > 10-year group versus the < 5-year group (odds ratio 0.44, p = 0.002), but the age at menarche showed no association. AIA manifested significantly earlier (≤ 6 months) as the time since LMP became shorter (< 5 years). CONCLUSION: AIA tends to manifest early after starting AI, but some cases show delayed onset. The incidence was significantly lower in patients with a duration of > 10 years since LMP. When the time since LMP was short, the onset of AIA was significantly earlier after starting AI administration.

Expression of p53, Ki-67, E-cadherin, N-cadherin and TOP2A in triple-negative breast cancer.

BACKGROUND: Elucidation of the biological features of triple negative breast cancer (TNBC) is important for deciding treatment strategies. The expression of a number of biomarkers in TNBC was analyzed to elucidate those features. PATIENTS AND METHODS: The subjects were 134 TNBC patients. Immunohistochemical staining was employed to analyze for eight biomarkers: cytokeratin 5/6 (CK5/6), epidermal growth factor receptor (EGFR), p53, Ki-67 antigen (Ki-67), E-cadherin, N-cadherin, topoisomerase 2 alpha (TOP2A) and B-cell lymphoma 2 (BCL-2), which were then correlated with the nuclear grade (NG), tumor diameter, and the presence/absence of lymph node metastasis, distant recurrence and lymphatic infiltration. RESULTS: Significantly more high than low NG TNBC exhibited positive p53, Ki-67, E-cadherin and TOP2A. High N-cadherin and TOP2A expression was shown significantly in TNBC with lymphatic infiltration, and N-cadherin was also significantly positively expressed in node metastasis-positive cases. EGFR and CK5/6 were positively expressed in high NG TNBC, but not significantly. CONCLUSION: Analysis for expression of p53, Ki-67, E-cadherin, N-cadherin and TOP2A is meaningful for deciding treatment strategies for TNBC.

Joint symptoms, aromatase inhibitor-related adverse reactions, are indirectly associated with decreased serum estradiol.

Background. Joint symptoms (JSs) are problematic adverse drug reactions (ADRs) of aromatase inhibitors (AIs). Involvement of decreased serum estradiol (SE) has been suggested. Patients and Methods. 104 postmenopausal breast cancer patients administered an AI were prospectively investigated regarding various clinical parameters, JS and hot flashes as ADRs, and the SE level. Results. JS manifested in 31.7% of patients and hot flashes in 18.3%. Chi-square testing showed a significantly higher incidence of JS in several patient strata: <55 years old, decreased SE, and elevated total cholesterol (TC). In univariate analysis, JS correlated significantly with a pre-AI % YAM of ≥80%, decreased SE, and elevated TC. Eight (7.7%) patients maintained SE at ≥5 pg/mL for >6 consecutive months, with no JS. In chi-square testing, hot flashes showed a significantly higher incidence in patients <55 years old. Conclusion. AI-ADRs occurred more readily in younger patients. Decreased SE may be indirectly involved in JS.

Serum estradiol should be monitored not only during the peri-menopausal period but also the post-menopausal period at the time of aromatase inhibitor administration.

BACKGROUND: Aromatase inhibitor (AI) therapy is being extensively used as postoperative adjuvant therapy in patients with hormone receptor-positive postmenopausal breast cancer. On the other hand, it has been reported that ovarian function was restored when AI was administered to patients who had undergone chemical menopause with chemotherapy or tamoxifen. However, there have been no reports of comprehensive monitoring of estradiol (E2) in breast cancer patients with ordinary menopause who were being administered AI. PATIENTS AND METHODS: Beginning in March 2008, regular monitoring of the serum levels of E2, luteinizing hormone (LH) and follicle-stimulating hormone (FSH) was performed for 66 postmenopausal breast cancer patients who had been started on AI therapy. For this study, we chose anastrozole as the AI. The assays of those hormones were outsourced to a commercial clinical laboratory. RESULTS: In 4 of the 66 patients the serum E2 level was decreased at 3 months but had then increased at 6 months, while in 2 other patients E2 was decreased at both 3 and 6 months but had increased at 9 months. CONCLUSION: The results indicate that, in some breast cancer patients with ordinary menopause, E2 rebounds following AI therapy. In the future, E2 monitoring should be performed for a larger number of patients being administered AI therapy. TRIAL REGISTRATION: Our trial registration number is 19-11-1211.

Clinical efficacy and problems with CT lymphography in identifying the sentinel node in breast cancer.

BACKGROUND: Combining a radioisotope with a dye-guided method is the best method for identification of the sentinel lymph nodes (SNs) in breast cancer. However, some institutions are limited to use of a dye-guided method alone. Recently, computed tomographic lymphography (CTLG) employing a nonionic contrast medium has achieved SN identification. PATIENTS AND METHODS: 218 patients with primary breast cancer and no clinical evidence of lymph node metastasis were studied. SN identification was performed by CTLG and a dye-guided method. The SN identification rate was analyzed for correlations with the clinicopathological findings. RESULTS: The SN identification rates were 96% with CTLG, 92% with the dye-guided method and 99% with both methods combined. The identification rates with CTLG and the combined method were significantly lower in node-positive patients compared to node-negative patients, and significantly lower with the combined method in vascular invasion-positive patients compared to negative patients. In addition, the SN identification rate with the dye-guided method was significantly lower in patients with a body mass index (BMI) of > or = 25, whereas the BMI did not affect the identification rate with CTLG or the combined method. Multiple SNs were detected in approximately 20% of the patients. CONCLUSION: Combined performance of CTLG and a dye-guided method enables identification of SNs prior to breast cancer surgery. That SN identification is easier compared with by the dye-guided method alone, and the identification rate is improved compared with either method alone. The combination of methods was especially useful in obese patients. For patients with multiple SNs, the combination has the further advantage of enabling accurate SN biopsy. CTLG may yield false-negative findings in node-positive patients and patients with lymph vessel obstruction.

Thymidine phosphorylase and dihydropyrimidine dehydrogenase are predictive factors of therapeutic efficacy of capecitabine monotherapy for breast cancer-preliminary results.

Capecitabine monotherapy was administered for 25 patients with advanced or recurrent breast cancer, and the clinical therapeutic efficacy and its relationship to expression of 5-fluorouracil-related enzymes (i. e., thymidine phosphorylase (TP), thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD)) were investigated. The expressions of TP, TS and DPD were determined by immunohistochemical staining techniques and rated using a scoring system of 1~4. The expression score for TP/DPD showed a statistically significant correlation with the clinical response, whereas the expression score for TP/TS also showed a correlation but it was not statistically significant. The number of patients was small, but the results revealed the potential of application of the TP/DPD expression score as a factor for predicting the efficacy of the drug in individual patients.

Screening for basal marker expression is necessary for decision of therapeutic strategy for triple-negative breast cancer.

BACKGROUND: Triple-negative breast cancer (estrogen receptor-negative, progesterone receptor-negative and Her2-negative) can be classified into two subtypes: basal and non-basal phenotype. Among these subtypes the basal phenotype is associated with poor outcome. Ordinarily, clinicopathological testing involves only screening for ER, PgR and Her2, and for this reason the therapeutic approach that is decided for triple-negative disease is usually the same regardless of the subtype. METHODS: Immunohistochemical staining was performed for the CK5/6, CK14, and CK17 basal markers in 66 triple-negative patients for the purpose of classifying as basal or non-basal phenotype, and the clinicopathology was investigated. RESULTS: Forty (60.1%) were the basal phenotype. Compared with the non-basal phenotype, the basal phenotype lesions were significantly larger in diameter, higher incidences of EGFR-positive and a high nuclear grade. In the node-negative group the basal phenotype clearly showed those same clinicopathological differences and a higher incidence of distal recurrence compared with the non-basal phenotype. CONCLUSIONS: Although there was the small number of the patients, this study results show that it is important to perform basal marker immunohistochemical staining and classify lesions as the basal or the non-basal phenotype, since this will aid in deciding the therapeutic strategy for triple-negative breast cancer.

A population-based dietary intervention trial in a high-risk area for stomach cancer and stroke: changes in intakes and related biomarkers.

BACKGROUND: Dietary intervention is one of the important fields in cancer and cardiovascular disease prevention. The Hiraka Dietary Intervention Study is a community-based randomized cross-over trial designed to develop an effective dietary modification tool and system in an area with high mortality of stomach cancer and stroke. METHODS: The subjects were 550 healthy volunteers and were randomized into two groups with tailored dietary education to decrease sodium intake and to increase vitamin C and carotene intakes either in the first year (intervention group) or in the second year (control group). Dietary changes were assessed using a validated self-administered diet history questionnaire, fasting blood samples, and 48-hour urine samples, which were obtained before and after the one year period. RESULTS: During the first year, changes differed significantly between the intervention and control group for both dietary sodium intake (-384 and +255 mg/day, intervention and control respectively, p < 0.001) and urinary sodium excretion (-1003 and -84 mg/day, p < 0.001). Although favorable net changes were also observed in dietary carotene (+418 and +220 mug/day, p < 0.05) and vitamin C (+13 and +2 mg/day, p < 0.05), the serum level differences were modest (+13 and -25 mg/L, p = 0.09 for carotene, +0.1 and -0.5 mg/L, p = 0.07 for ascorbic acid). CONCLUSION: The present dietary intervention strategy effectively decreased sodium and increased carotene and vitamin C intakes, although the former was more distinct.