Influence of alcohol sensitivity on bone metastases and skeletal-related events in primary operable breast cancer: A retrospective cohort study.

BACKGROUND: Bone metastases in breast cancer patients are a common concern for medical doctors and dentists. Bone-modifying agents, which are necessary to prevent skeletal-related events (SREs), are associated with osteonecrosis of the jaw as an adverse side effect. Hypersensitivity to alcohol is an unfavorable response caused by deficiency of aldehyde dehydrogenase-2 (ALDH2) activity. Inactive ALDH2 is associated with osteoporosis, but its influence on bone metastases is unclear. The aim of our study was to evaluate the effects of alcohol sensitivity on bone metastases and SREs in primary operable breast cancer patients. METHODS: We retrospectively analyzed patients who were administered docetaxel, an anti-tumor agent, for histologically diagnosed breast cancer between April 2004 and September 2015. Alcohol sensitivity was assessed based on medical records of hypersensitivity to alcohol. The primary endpoint was time to bone metastases and the secondary endpoint was time to first SRE from the initial docetaxel administration. Data were stratified by alcohol sensitivity and tumor stages, and differences were estimated by the Kaplan-Meier method. Prognostic risk factors were analyzed by the multivariate Cox proportional hazards model. RESULTS: The median follow-up period of patients with high sensitivity to alcohol (n = 45) was 54 months and that for those with low sensitivity (n = 287) was 64 months. Stratification by alcohol sensitivity revealed that tumor stage exhibited significant correlations with the cumulative incidence of bone metastases in low-sensitivity patients; however, no differences were found in high-sensitivity patients. In multivariate analysis, alcohol sensitivity was a significant prognostic risk factor for bone metastases (HR 2.721, 95% CI 1.268-5.841, P = 0.010). CONCLUSION: Alcohol sensitivity may be a prognostic risk factor for bone metastases. More detailed genetic investigations and metabolic analyses are needed.

Professional Oral Care Reduces Carcinogenic Acetaldehyde Levels in Mouth Air of Perioperative Esophageal Cancer Patients: A Prospective Comparative Study.

Acetaldehyde is a potential carcinogen for esophageal cancer, and some oral microorganisms produce acetaldehyde from ethanol or glucose. In this prospective study, we examined the influence of professional oral care on acetaldehyde levels in mouth air of esophageal cancer patients. Acetaldehyde concentrations in mouth air and breath were measured by a portable gas chromatograph, and acetaldehyde production from oral microbiota was also evaluated. Samples were taken from 21 esophageal cancer patients (median age 68 years) and 20 age-matched healthy volunteers (control group) before and after oral care. Post-operative samples were also taken from 17 patients who had undergone surgery. All samples (mouth air, breath, and saliva) were collected 2 to 3 hours after lunch. Oral microbial samples were prepared from saliva. Genotype analysis of alcohol dehydrogenase 1B (ADH1B) and aldehyde dehydrogenase-2 (ALDH2) genes revealed no significant differences in the genotypes between the two groups. In the control group, acetaldehyde levels in mouth air showed no significant changes after oral care, while the amount of microbial acetaldehyde production from ethanol was significantly decreased. By contrast, among the patients, acetaldehyde levels in mouth air were significantly decreased after oral care and after operation, while the amount of microbial acetaldehyde production from ethanol showed no significant changes. Moreover, microbial acetaldehyde production from glucose was significantly decreased after operation. Overall, oral health was poorer in the patient group. In conclusion, professional oral care for esophageal cancer patients is effective for reducing acetaldehyde levels in mouth air due to the reduction of microbial count.

Metabolic property of acetaldehyde production from ethanol and glucose by oral Streptococcus and Neisseria.

Acetaldehyde is known to be carcinogenic and produced by oral bacteria. Thus, bacterial acetaldehyde production might contribute to oral cancer. Therefore, we examined bacterial acetaldehyde production from ethanol and glucose under various conditions mimicking the oral cavity and clarified the metabolic pathways responsible for bacterial acetaldehyde production. Streptococcus mitis, S. salivarius, S. mutans, Neisseria mucosa and N. sicca were used. The bacterial metabolism was conducted at pH 5.0-8.0 under aerobic and anaerobic conditions. The production of acetaldehyde and organic acids was measured with gas chromatography and HPLC, respectively. Bacterial enzymes were also assessed. All of the bacteria except for S. mutans exhibited their greatest acetaldehyde production from ethanol at neutral to alkaline pH under aerobic conditions. S. mutans demonstrated the greatest acetaldehyde from glucose under anaerobic conditions, although the level was much lower than that from ethanol. Alcohol dehydrogenase and NADH oxidase were detected in all of the bacteria. This study revealed that oral indigenous bacteria, Streptococcus and Neisseria can produce acetaldehyde, and that such acetaldehyde production is affected by environmental conditions. It was suggested that alcohol dehydrogenase and NADH oxidase are involved in ethanol-derived acetaldehyde production and that the branched-pathway from pyruvate is involved in glucose-derived acetaldehyde production.

Exhaled acetone and isoprene in perioperative lung cancer patients under intensive oral care: possible indicators of inflammatory responses and metabolic changes.

One of the most severe complications of lung resection is postoperative pneumonia, and its prevention and prediction are critical. Exhaled acetone and isoprene are thought to be related to metabolism; however, little is known on their relationship with bacteria living in the oral cavity or their meaning in the acute phase in perioperative lung cancer patients. We measured acetone and isoprene in exhaled breath of 13 Japanese patients with lung cancer (3 women and 10 men, age range 62-82 years, mean 72.4 years) before breakfast during hospitalization, and compared with two acute-phase proteins, C-reactive protein (CRP) and albumin in blood serum, as well as the total number of bacteria in saliva and their activity to produce acetone and isoprene. Before operation, intensive oral care was carried out for each patient to prevent postoperative pneumonia, and swallowing and cough reflexes were measured for 12 of 13 patients to assess risk of postoperative pneumonia. Breath and saliva were sampled before intensive oral care (T1), after oral care but before operation (T2), and after operation (T3) during hospitalization. The total number of oral bacteria in saliva decreased significantly from T1 to T2 among 13 patients. No acetone or isoprene was detected from saliva after in vitro incubation under anaerobic or aerobic conditions, but both acetone and isoprene were detected in breath. After operation, breath acetone correlated significantly with CRP (Spearman's ρ = 0.559, P = 0.03), but not with albumin. Breath isoprene correlated significantly with albumin (Spearman's ρ = 0.659, P = 0.008), but not with CRP after operation. Although the number of subjects was small, our results support the hypothesis that breath acetone and isoprene may be related with these acute-phase proteins, which reflect inflammatory reactions and subsequent changes in metabolism in the early postoperative phase of lung resection.

[Current Status of Preoperative Professional Oral Care by Dentists for Elderly Patients Undergoing Lung Resection and Occurrence of Postoperative Pneumonia].

Pneumonia in elderly people is mainly caused by silent aspiration due to an age-related impairment of cough and swallowing reflexes. Because most of the patients with lung cancer are elderly people, we hypothesized that the age-related impairment of these protective reflexes might exist or occur in patients undergoing lung surgery, and cause postoperative pneumonia. We revealed that many elderly patients showed depressed swallowing reflex even before surgery and transient attenuation of cough reflex after surgery, and that postoperative pneumonia occurred only in the patients whose cough and/or swallowing reflex was abnormal postoperatively. Then, we prospectively showed that 30 elderly patients who received perioperative intensive oral care, including professional assessment of oral status, dental cleaning, and patient education for self-oral care by dentists, followed by intensive oral care by intensive care unit nurses, and encouragement of self-oral care by floor nurses, did not develop pneumonia after lung resection. In this study, we retrospectively reviewed the execution status of professional oral care by dentists and the occurrence of postoperative pneumonia in 159 consecutive patients aged 65 or older undergoing lung resection from 2013 to 2014. Thoracic surgeons in our institute asked dentists to provide professional oral care before lung resection only in 30.3% of the subjects in 2013, and 45.8% in 2014. Postoperative pneumonia occurred in 3 out of 76 subjects(3.9%)in 2013, and 1 out of 83(1.2%) in 2014. In 2013, 1 patient who did not receive preoperative professional oral care developed aspiration pneumonia postoperatively followed by acute exacerbation of idiopathic pulmonary fibrosis and in-hospital death. We need to make an effective system to provide preoperative professional oral care by dentists especially for elderly patients and high-risk patients before lung resection.

Analysis of ketone bodies in exhaled breath and blood of ten healthy Japanese at OGTT using a portable gas chromatograph.

Ketone bodies including acetone are disease biomarkers for diabetes that sometimes causes severe ketoacidosis. The present study was undertaken to clarify the significance of exhaled acetone and plasma ketone bodies at bedside in a clinical setting. The oral glucose tolerance test (OGTT) was performed in 10 healthy Japanese volunteers (five females and five males). Exhaled breath acetone and volatile sulfide compounds (VSCs) in mouth air were measured simultaneously with blood sampling during the OGTT using a portable gas chromatograph equipped with an In2O3 thick-film type gas sensor and a VSC monitor. Acetone, ß-hydroxybutyrate (ß-OHB) and acetoacetate (AcAc) in blood plasma as well as glucose and insulin were examined. Oral conditions were examined based on the Community Periodontal Index (CPI) by one dentist. In addition, the same type of analysis was applied to two uncontrolled type 2 diabetes mellitus patients hospitalized at Tohoku University Hospital. Exhaled acetone was measured at the same time as blood withdrawal in the morning before breakfast and at night before bed at the beginning, the middle, and the end of hospitalization. All volunteers showed normal OGTT patterns with no ketonuria and periodontitis; however, there were significant correlations between breath acetone and plasma ß-ΟΗΒ and between breath acetone and plasma AcAc under fasting conditions. Breath acetone of the type 2 diabetes mellitus patients showed positive correlations with plasma glucose when the level of plasma glucose tended to decrease during hospitalization. In spite of a very limited number of cases, our results support the idea that exhaled breath acetone may be related to plasma ß-OHB and AcAc, which reflect glucose metabolism in the body.

Detection and identification of oral anaerobes in intraoperative bronchial fluids of patients with pulmonary carcinoma.

Postoperative pneumonia may occur when upper respiratory tract protective reflexes such as cough and/or swallowing reflexes are impaired; thus, silent aspiration of oral bacteria may be a causative factor in postoperative pneumonia. This study aimed to quantify and identify bacteria in intraoperative bronchial fluids and to evaluate the relationship between impairment of cough/swallowing reflexes and silent aspiration of oral bacteria in elderly patients. After obtaining informed consent, cough and swallowing reflexes were assessed using an ultrasonic nebulizer and a nasal catheter, respectively. Using a micro-sampling probe, intraoperative bronchial fluids were collected from nine subjects with pulmonary carcinoma and cultured anaerobically on blood agar plates. After 7 days, CFUs were counted and isolated bacteria were identified by 16S rRNA gene sequencing. Four subjects (aged 71.0 ± 8.4 years) had impaired swallowing reflexes with normal cough reflexes, whereas five subjects (73.6 ± 6.5 years) had normal cough and swallowing reflexes. The bacterial counts (mean CFU ± SD) tended to be higher in intraoperative bronchial fluids of subjects with impaired swallowing reflexes ([5.1 ± 7.7] × 10(5)) than in those of subjects with normal reflexes ([1.2 ± 1.9] × 10(5)); however, this difference was not statistically significant. Predominant isolates from intraoperative bronchial fluids were Streptococcus (41.8%), Veillonella (11.4%), Gemella (8.9%), Porphyromonas (7.6%), Olsenella (6.3%) and Eikenella (6.3%). These findings indicate that intraoperative bronchial fluids contain bacteria, probably derived from the oral microbiota, and suggest that silent aspiration of oral bacteria occurs in elderly patients irrespective of impairment of swallowing reflex.

Novel recombinant congenic mouse strain developing arthritis with enthesopathy.

Based on the hypothesis that the complex pathological and immunological manifestations of rheumatoid arthritis (RA) and the related diseases are under the control of multiple gene loci with allelic polymorphism, a recombinant congenic mouse strain was prepared between an MRL/Mp-lpr/lpr (MRL/lpr) strain, which develops arthritis resembling RA, and a non-arthritic strain C3H/HeJ-lpr/lpr (C3H/lpr). In MRL/lpr x (MRL/lpr x C3H/lpr) F1 mice, the mice developing severe arthritis were selected based on joint swelling to further continue intercrosses, and then an McH-lpr/lpr-RA1 (McH/lpr-RA1) strain was established and its histopathological phenotypes of joints and autoimmune traits were analyzed. Arthritis in McH/lpr-RA1 mice developed at a higher incidence by 20 weeks of age, compared with that in the MRL/lpr mice, who had severe synovitis (ankle, 60.3%; knee, 65.1%), and also fibrous and fibrocartilaginous lesions of articular ligamenta resembling enthesopathy (ankle, 79.4%; knee, 38.1%), resulting in ankylosis. The lymphoproliferative disorder was less, and serum levels of IgG and IgG autoantibodies including anti-dsDNA and rheumatoid factor were lower than those of both MRL/lpr and C3H/lpr strains. McH/lpr-RA1 mice may provide a new insight into the study of RA regarding the common genomic spectrum of seronegative RA and enthesopathy.

A new portable sulfide monitor with a zinc-oxide semiconductor sensor for daily use and field study.

OBJECTIVE: For measuring oral malodor in daily clinical practice and in field study, we developed and evaluated a highly sensitive portable monitor system. METHODS: We examined sensitivity and specificity of the sensor for volatile sulfur compounds (VSC) and obstructive gases, such as ethanol, acetone, and acetaldehyde. Each mouth air provided by 46 people was measured by this monitor, gas chromatography (GC), and olfactory panel and compared with each other. Based on the result, we used the monitor for mass health examination of a rural town with standardized measuring. RESULTS: The sensor detected hydrogen sulfide, methyl mercaptan, and dimethyl sulfide with 10-1000 times higher sensitivity than the other gases. The monitor's specificity was significantly improved by a VSC-selective filter. There were significant correlations between VSC concentration by the sulfide monitor and by GC, and by organoleptic score. Thirty-six percent of 969 examinees had oral malodor in a rural town. Seventy-eight percent of 969 examinees were motivated to take care of their oral condition by oral malodor measuring with the monitor. CONCLUSIONS: The portable sulfide monitor was useful to promote oral health care not only in clinics, but also in field study. The simple and quick operation system and the standardized measuring make it one of parameters of oral condition.