Studies on urinary excretion and variability of dietary iodine in healthy Japanese adults.

The daily consumption of iodine in Japan is higher than in most countries, and there are few reports on iodine metabolism and variance of habitual iodine ingestion in an iodine-sufficient area. To elucidate the patterns of short-term urinary iodine excretion (UIE) and long-term variability of habitual iodine intake, the urinary iodine excretion process after a high dietary iodine load of 3 mg was observed in eight Japanese adults under strict supervision with complete urine collections for three days. In addition, estimated UIE and dietary iodine intake (DII) were assessed in 24 university students using repeated spot urine samples of ten consecutive days and a food frequency questionnaire in each of the four seasons. Approximately 50, 75 and 90% of orally ingested iodine was excreted into the urine at 8, 13 and 22 hours after ingestion, respectively. Almost an equal amount of ingested iodine in meals was cleared within 33.5 h after eating with a maximum excretion rate at 3-4 h. There was a high fluctuation in the UIE and DII in the university students. The intra- and inter-individual crude coefficients of variation were 123 or 294.7% for UIE, and 58.3 or 88.7% for DII, respectively, indicating a higher variance of habitual iodine intake than in other countries. The frequency of occurrence for UIE above 3 mg was every 43 days. Rapid renal clearance of iodine and high variability as well as low frequency of dietary iodine intake might prevent people from being exposed to an excess iodine intake over the long term in Japan.

The relationship between BRCA-associated breast cancer and age factors: an analysis of the Japanese HBOC consortium database.

BRCA1/2 pathogenic variant prevalence in Japanese breast cancer is unclear. Here, we analyzed BRCA1/2 pathogenic variant prevalence with a particular focus on age factors, using the Japanese HBOC consortium database. All registered subjects were Japanese individuals who underwent BRCA1/2 genetic testing from January 1996 to July 2017 according to the Japanese HBOC consortium database. Cases were extracted and analyzed for each evaluation item. Overall BRCA1 and BRCA2 pathogenic variant prevalence was 11.2% and 9.0% in the cohort of 2366 proband patients, respectively. The age at onset of breast cancer for patients with BRCA1/2 pathogenic variants was significantly lower than that for patients without a BRCA1/2 pathogenic variant. In both BRCA1/2 patients, ages at onset were not statistically significantly different between two subtype groups (ER-positive vs. TNBC). We analyzed the BRCA1/2 pathogenic variant prevalence among age groups in patients with no family history of breast or ovarian cancer. In the TNBC group, the rate of genetic variants was more frequent among younger patients. Our results demonstrated that early breast cancer onset is associated with a BRCA1/2 pathogenic variant in the Japanese population. Younger TNBC patients were more likely to have a BRCA1/2 pathogenic variant irrespective of a family history of breast or ovarian cancer.

Efficacy of a New Post-Mouthwash Intervention (Wiping Plus Oral Nutritional Supplements) for Preventing Aspiration Pneumonia in Elderly People: A Multicenter, Randomized, Comparative Trial.

BACKGROUND/AIMS: Aspiration pneumonia is a common cause of death among the elderly (≥90-year-old) in nursing homes. Studies suggest that its incidence could be reduced by oral care interventions. We aimed to evaluate the efficacy of a new oral care intervention: wiping plus oral nutritional supplements (ONS). METHODS: This prospective observational study was conducted in 252 patients (age 88.0 ± 6.5 years) in 75 nursing homes, rehabilitation hospitals, and other care facilities. Patients were randomly divided into an intervention group (n = 74) and a control group (n = 107), whose members received conventional oral care. Body mass index, activities of daily living (Barthel index), and complete blood count and biochemistry parameters were measured at 2, 4, 6, and 8 months. RESULTS: The cumulative incidence of pneumonia at 8 months tended to be lower in the intervention than in the control group (7.8 vs. 17.7%, p = 0.056) and was significantly lower for men in the intervention group (p = 0.046). CONCLUSIONS: Our new intervention "wiping plus providing ONS" method appears to help prevent aspiration pneumonia, thereby reducing mortality risk. In this study, we disseminate information on how this method is used in Japan.

[A case of triple-negative breast cancer achieved pCR by epirubicin and cyclophosphamide(EC)therapy followed by gemcitabine plus paclitaxel combination preoperative therapy].

A 59-year-old woman was diagnosed with triple-negative breast cancer(TNBC)(T2N0M0)and treated with primary systemic therapy. The patient was treated with 4 courses of epirubicin and cyclophosphamide(EC)therapy every 3 weeks, followed by weekly gemcitabine-paclitaxel combination therapy. As she was judged to have achieved a partial response(PR) by ultrasound and CT examination after eight courses, she underwent partial resection of the left breast. CR was revealed by the pathological examination of the resected specimen. Gemcitabine-paclitaxel combination therapy seems to be a one of the useful preoperative chemotherapies for TNBC.

Body weight reduction by exercise increases the urinary 3-methylhistidine excretion level with relatively positive nitrogen, sodium, and potassium balances when compared to dietary restriction.

Background: Regarding changes in muscle mass, differences due to types of exercise and/or nutritional interventions, and associations with nutrient balances are still unclear. Methods: To estimate changes in muscle mass during a body weight loss program using either a diet or exercise regimen, we investigated levels of muscle mass-related indices, and body contents of nitrogen, sodium, and potassium as measured by the balance method. Six healthy young adult male volunteers participated in two 10-day crossover experiments (20 days total). The first 5 days comprised an adjustment period (energy intake, 2656 ± 367 kcal/day (mean ± standard deviation)). During the second 5-day period, the participants either reduced their energy intake to 1770 ± 244 kcal/day (diet regimen) or exercised on a bicycle ergometer to expend 886 ± 122 kcal/day (exercise regimen). Results: The nitrogen, sodium, and potassium balances were significantly more positive during the exercise regimen than during the diet regimen. The urinary excretion levels of creatinine, 3-methylhistidine (3-MH), aldosterone, and catecholamines, and the 3-MH/creatinine ratio were significantly increased only during the exercise regimen. Conclusions: The exercise regimen suppresses the decrease in muscle mass-related indices during body weight loss compared to the diet regimen with a relatively positive state of whole-body protein, sodium, and potassium balances, accompanied by an increase in sympathetic/adrenal cortical functions.

[The clinical study of familial breast cancer - now and the problems].

The clinical features of familial breast cancer are characterized by early onset, high frequency of bilateral breast cancer, and multiple malignancies of other organs. It is strongly suggested that genetic factors contribute to familial breast cancer. The causative genes now identified are BRCA1 and BRCA2. This disease is called hereditary breast ovarian cancer syndrome (HBOC)because breast cancer and ovarian cancer are clustered in the kindred confirmed BRCA mutation. As for BRCA related breast cancer, early onset and highly frequent bilateral breast cancer are characteristic. In addition, the histological grade is high and the positive rate of estrogen receptors is low in BRCA1-related breast cancer. Gene diagnosis of BRCA is useful when choosing a surgical method, chemotherapy, or a surveillance of mutation carriers. The problem in Japan is that the treatment is very expensive, with poor understanding of HBOC of by clinicians and as yet immature genetic counseling system.

Oncocytic adrenocortical carcinoma.

Only 17 cases of oncocytic adrenocortical carcinoma have been reported in the English literature. Here, we report an incidental case of oncocytic adrenocortical carcinoma. The patient was a 69-year-old man with the chief complaint of abdominal pain. Abdominal computed tomography revealed a left adrenal tumor. No hormonal symptoms were observed. The excised tumor was whitish, encapsulated, and 75 x 60 x 45 mm in size. Large polygonal tumor cells were arranged in a generally diffuse architecture and exhibited abundant eosinophilic granular cytoplasm. Nuclear atypia with atypical mitotic figures and capsular and sinusoidal invasions were observed. The tumor cells were immunopositive for vimentin, neuron-specific enolase, and synaptophysin but not for alpha-inhibin, melan A, or p53. Diffuse and strong immunopositivity with an antimitochondrial antibody proved that this tumor was truly oncocytic. Upon review of previous cases of oncocytic adrenocortical tumors, we reconsidered the diagnostic findings of the potential for malignancy.

Remnant lipoprotein metabolism is improved more when body weight is reduced by exercise than by dietary restriction.

BACKGROUND: Remnant lipoprotein levels during weight-loss programs have not been examined in detail. We investigated the effects of reducing body weight by exercise and by dietary restriction on lipid metabolism including remnant-like particle-cholesterol (RLP-C) and apolipoprotein B48 (apo B48). METHODS: Six adult male volunteers participated in 2 experiments over 10 days. The first 5 days were an adjustment period (energy intake, 2656+/-150 kcal/day; mean+/-SEM). During the second 5 days, the participants either exercised on a bicycle ergometer to consume 886+/-50 kcal/day or reduced their energy intake to 1770+/-100 kcal/day. RESULTS: Serum triglyceride (TG) and RLP-C levels were significantly lower, whereas the increase in high density lipoprotein-cholesterol (HDL-C) level was significantly larger after exercise than after dietary restriction. We measured changes (Delta) in serum levels and identified positive correlations between Delta insulin and Delta TG, Delta apo B48 (p<0.05) and Delta RLP-C (p=0.050) only during exercise. CONCLUSIONS: Reducing body weight by exercise has more beneficial effects on lipid metabolism than a dietary approach, and improved insulin resistance accompanies the decrease of serum remnant lipoprotein levels.

Increase in insulin secretion and decrease in muscle degradation by fat-free milk intake are attenuated by physical exercise.

BACKGROUND: Protein intake, particularly branched chain amino acids (BCAAs), and exercise have opposing actions on insulin secretion, but the same action on protein anabolism. We examined the effects of BCAA-rich fat-free milk intake and/or exercise on levels of insulin secretion and indices related to muscle protein metabolism in order to assess the potency of dietary and exercise therapies against metabolic and locomotive disorders. METHODS: Eight adult female volunteers participated in all four 24 h experiments; control diet intake with or without exercise, and fat-free milk-containing diet intake with or without exercise. Fat-free milk was replaced with one-sixth of all foods in the control diet. Exercise was set at an equal-energy level as fat-free milk. Urine and fasting blood samples were collected for each experiment. RESULTS: Urinary C-peptide immunoreactivity excretion and serum insulin levels were significantly higher, but urinary 3-methyl-histidine excretion levels were significantly lower with low urinary adrenaline and dopamine excretion in the fat-free milk-containing diet than in the control diet. These findings were reduced by exercise with high urinary adrenaline and noradrenaline excretion. CONCLUSIONS: BCAA-rich fat-free milk intake enhanced insulin secretion and suppressed muscle protein degradation, but these effects are attenuated by exercise accompanied with increase in catecholamine secretion.

A case of familial breast cancer with double heterozygosity for BRCA1 and BRCA2 genes.

We report an extremely rare case of familial breast cancer with deleterious germline mutations in both BRCA1 and BRCA2 genes, of which, to date, no such case has been reported among Japanese breast/ovarian cancer patients. Genetic testing of the family members indicated that the same double heterozygosity for BRCA1 and BRCA2 genes was transmitted to the paternal cousin, and the same BRCA2 mutation to the younger sister with bilateral breast cancer, younger brother with stomach cancer, and proband's son and daughter without cancer. Immunohistochemical analysis of BRCA protein expression was performed using breast cancer tissues from the proband with double heterozygosity for BRCA1 and BRCA2 genes and from her sibling without BRCA1 mutation but with BRCA2 mutation. There was no staining of either BRCA in the proband and no staining of BRCA2 in the sibling.

Clinicopathological study of non-palpable familial breast cancer detected by screening mammography and diagnosed as DCIS.

BACKGROUND: Recent widespread use of screening mammography has led to increased detection rates of non-palpable breast cancer. This study aimed to evaluate the clinicopathological features of non-palpable ductal carcinomas in situ of the breast that were detected by screening mammography of patients with a family history of breast cancer. METHODS: We selected 6 Japanese patients diagnosed with non-palpable breast cancer with self-reported family history of breast cancer. Mutations in BRCA1 and BRCA2 were evaluated with germ line genetic testing and immunohistochemistry (IHC) using resected specimens. Pathological features, such as estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2, were also evaluated. RESULTS: The patients (ages 41-67 years; mean 53.5) had 7 tumors with one patient having synchronous bilateral breast cancer. Breast cancer was suspected from the microcalcification in 5 tumors and the distortion in 2 tumors by mammography and diagnosed by biopsy. Breast-conserving surgery was performed in 2 patients and mastectomy was performed in 4 patients. Genetic testing revealed BRCA2 gene germ line mutation in three patients. IHC of BRCA was consistent with BRCA2 mutation status. CONCLUSIONS: The family history of breast cancer patients may lead one to suspect familial breast cancer and screening mammography is useful for the early detection of these cancers. IHC of BRCA showed staining results that were consistent with BRCA genetic testing, suggesting that it has the potential to be a useful tool in clinical practice.

Multiple metastatic malignant melanoma presenting intraluminal gallbladder bleeding.

We report a case of malignant melanoma of unknown primary origin presenting metastasis in various organs as well as intraluminal gallbladder bleeding due to gallbladder metastasis. A 58-year-old woman was diagnosed with stage IV metastatic malignant melanoma. Because she exhibited acute cholecystitis and hemobilia due to malignant melanoma of the gallbladder, laparoscopic cholecystectomy was performed to relieve the symptoms. The resected gallbladder specimen showed a pedunculated black mass indicating malignant melanoma. Pathologic examination and immunohistochemical analysis revealed malignant melanoma of the gallbladder. Only a few cases of gallbladder malignant melanoma presenting hemobilia have been reported; here we present our case, including the experience of multidisciplinary treatment.

Hemorrhagic cytomegalovirus colitis in a postoperative colon cancer patient.

We report a case of hemorrhagic cytomegalovirus (CMV) colitis, occurring in a postoperative patient due to a weakened immune system. An 85-year-old woman with a medical history, including chronic renal failure treated with oral administration of prednisolone, underwent colectomy due to an ascending colon cancer. While the postoperative course was favorable, she exhibited acute severe abdominal pain and massive bloody discharge after 11 days of surgery. Her colonoscopic examination showed multiple longitudinal ulcers on the anastomosis. In addition to these endoscopic findings, her past medical history helped suggest CMV colitis. Because serological testing revealed positive CMV antigen, she was finally given a diagnosis of CMV colitis and received intravenous ganciclovir for the initial treatment. Hemorrhagic CMV colitis after colectomy is an important postoperative complication; we therefore present our case with diagnosis and treatment experience.

Three cases of kindred with familial breast cancer in which carrier detection by BRCA gene testing was performed on family members.

We performed presymptomatic carrier detection by BRCA gene testing of the family members of three familial breast cancer kindred diagnosed with pathogenetic mutation in BRCA genes. All members were over 20 years of age. We explained familial breast cancer and BRCA gene testing, and obtained autonomic consent before gene testing. Genetic testing revealed twins in a family were dizygotic. In another family bilateral breast cancer occurred in a carrier after five years of genetic testing. Carriers are at high risk of breast cancer and have to receive breast cancer screening and familial tumor counseling. Non-carriers are at the same risk of breast cancer as the general population.

A case of primary malignant lymphoma of the breast with an unusual ultrasound image.

The patient was a 50-year-old woman with a palpable tumor and pain in the right breast in May of 2008. The tumor was then diagnosed as an atheroma. The tumor enlarged rapidly in June, and the pain and the redness had worsened. The patient was then referred to our hospital. The tumor was in the upper inner quadrant of the right breast with surface redness, measuring about 3 cm. In the mammographic (MMG) findings, the tumor shadow was in the upper inner quadrant of the right breast and was observed to be circular and have a high density with a plain boundary and slightly roughed edges. In the ultrasonographic (US) findings, an oval-shaped high echoic region was found subcutaneously in the right breast. Because the high echoic area was subdivided in the partition of the low echoic string, it looked like a pebbled wall. Upon core needle biopsy, this case was diagnosed as malignant lymphoma. After comparing the histopathology and the US image, it was determined that the pebbled wall-shaped image was due to lymphocyte infiltration of the tissue. The US image was peculiar and we report this case as a peculiar example of malignant lymphoma.