Identification of TPI1 As a potential therapeutic target in pancreatic cancer with dependency of TP53 mutation using multi-omics analysis.

Mutations of KRAS, CDKN2A, TP53, and SMAD4 are the four major driver genes for pancreatic ductal adenocarcinoma (PDAC), of which mutations of KRAS and TP53 are the most frequently recognized. However, molecular-targeted therapies for mutations of KRAS and TP53 have not yet been developed. To identify novel molecular targets, we newly established organoids with the Kras mutation (KrasmuOR) and Trp53 loss of function using Cre transduction and CRISPR/Cas9 (Krasmu/p53muOR) from murine epithelia of the pancreatic duct in KrasLSL-G12D mice, and then analyzed the proteomic and metabolomic profiles in both organoids by mass spectrometry. Hyperfunction of the glycolysis pathway was recognized in Krasmu/p53muOR compared with KrasmuOR. Loss of function of triosephosphate isomerase (TPI1), which is involved in glycolysis, induced a reduction of cell proliferation in human PDAC cell lines with the TP53 mutation, but not in PDAC or in human fibroblasts without TP53 mutation. The TP53 mutation is clinically recognized in 70% of patients with PDAC. In the present study, protein expression of TPI1 and nuclear accumulation of p53 were recognized in the same patients with PDAC. TPI1 is a potential candidate therapeutic target for PDAC with the TP53 mutation.

Aging-Related Metabolome Analysis of the Masseter Muscle in Senescence-Accelerated Mouse-Prone 8.

Frailty is a vulnerable state that marks the transition to long-term care for older people. Early detection and prevention of sarcopenia, the main symptom of frailty, are important to ensure an excellent quality of life for older people. Recently, the relationship between frailty, sarcopenia, and oral function has been attracting attention. This study aimed to clarify the changes in metabolites and metabolic pathways due to aging in the masseter muscle of senescence-accelerated mouse-prone 8 (SAMP8) mice. A capillary electrophoresis-mass spectrometry metabolome analysis was performed on the masseter muscle of 12-week-old, 40-week-old, and 55-week-old mice. The expression of enzymes involved in metabolome pathways considered to be related to aging was confirmed using reverse transcription polymerase chain reaction. Clear metabolic fluctuations were observed between 12, 40-week-old, and 55-week-old SAMP8 mice. The extracted metabolic pathways were the glycolysis, polyamine metabolome, and purine metabolome pathways. Nine fluctuated metabolites were common among the groups. Spermidine and Val were increased, which was regarded as a characteristic change in the masseter muscle due to aging. In conclusion, the age-related metabolic pathways in SAMP8 mice were the glycolysis, polyamine metabolome, and purine metabolome pathways. The increased spermidine and Val levels in the masseter muscle compared with the lower limbs are characteristic changes.

Functional Expression of Mechanosensitive Piezo1/TRPV4 Channels in Mouse Osteoblasts.

Mechanical stress is an important regulatory factor in bone homeostasis. Mechanical stimulation of osteoblasts has been shown to elicit an increase in the concentration of intracellular free Ca2+ ([Ca2+]i). The pattern of functional expression of mechanosensitive ion channels remains unclear, however. Therefore, the purpose of this study was to investigate the pharmacological characteristics of [Ca2+]i in response to direct mechanical stimulation in osteoblasts. The morphological expression of mechanosensitive ion channels was also examined. Mouse osteoblast-like cells (MC3T3-E1 cells) were loaded with fura-2-acetoxymethyl ester, after which [Ca2+]i was measured. Increased levels of [Ca2+]i were observed in MC3T3-E1 cells in response to direct mechanical stimulation by means of a glass micropipette, but no desensitization. Application of a hypotonic solution also induced an increase in [Ca2+]i but was accompanied by a desensitizing effect. Extracellular Gd3+, GsMTx4, or RN-1734 reversibly inhibited this mechanical stimulation-induced increase in [Ca2+]i, whereas no inhibitory effect was observed with HC030031 or clemizole. When osteoblasts were stimulated with Yoda1, an increase was observed in [Ca2+]i together with a significant desensitizing effect. Immunoreactivity against Piezo1 and TRPV4 channel antibodies was detected in MC3T3-E1 cells. These results suggest that osteoblasts express Piezo1 and TRPV4 channels, which are involved in mechanosensitive processes during mechanical stress.

Second Primary Metachronous Malignancies Occurring in Oral Cavity of Young Adult-A Case Report.

The incidence of oral cancer in Japan is increasing. Interestingly, the number of young patients with oral cancer is also rising. A 19-year-old man with no history of smoking or drinking alcohol presented with a 20×15-mm elastic, hard, protruding mass with a white surface on the right-hand margin of the tongue. A biopsy resulted in a diagnosis of a well-differentiated squamous cell carcinoma of the tongue, for which a partial resection was subsequently performed. During regular follow-up, the patient demonstrated no clinical or imaging abnormalities until 4 years and 9 months later, when erosion was observed at the right palatoglossal arch. A malignant tumor of the right palatoglossal arch was diagnosed based on cytology and imaging findings, and total resection of the lesion performed. Histopathological examination of the resected lesion revealed a moderately differentiated squamous cell carcinoma. Epithelial dysplasia on the right-hand margin of the tongue was diagnosed 4 years and 9 months after the second surgery and was subsequently resected. The patient's condition has been favorable for 7 years since the diagnosis of the second cancer, with no noted recurrence. This case emphasizes the importance of follow-up after initial treatment, as even young people, who are likely to have to endure long-lasting consequences from treatment, can develop metachronous cancer in the oral cavity.

Multicenter retrospective study of nivolumab for recurrent/metastatic oral squamous cell carcinoma.

OBJECTIVES: Immunotherapy with nivolumab for patients with recurrent/metastatic oral squamous cell carcinoma has not been evaluated. Here, we aimed to examine the efficacy, safety, and prognostic factors of nivolumab in these patients. MATERIALS AND METHODS: This multicenter retrospective observational study involved patients who received nivolumab between April 2017 and June 2019. The patient characteristics were evaluated for association with progression-free and overall survival. Progression-free and overall survival rates were calculated; parameters that were significant in the univariate analysis were used as explanatory variables. Independent factors for progression-free and overall survival were identified using multivariate analysis. RESULTS: Totally, 143 patients were included. The overall response and disease control rates were 27.3% and 46.2%, respectively. The median, 1- and 2-year progression-free survival rates were 2.7 months, 25.4%, and 19.2%, respectively; those for overall survival were 11.2 months, 47.3%, and 33.6%, respectively. The independent factors affecting progression-free survival were performance status and immune-related adverse event occurrence, whereas those affecting overall survival were performance status, target disease, and number of previous lines of systemic cancer therapy. Eight patients reported grade ≥3 immune-related adverse events. CONCLUSION: Nivolumab was effective for recurrent/metastatic oral squamous cell carcinoma treatment and was well tolerated by patients.

Factors associated with xerostomia in perimenopausal women.

OBJECTIVES: Various oral symptoms, including xerostomia and burning mouth syndrome, may occur in menopausal women. These symptoms reduce quality of life (QOL). However, the actual condition of xerostomia after menopause is not clear. The purpose of this study was to reveal the factors associated with xerostomia in perimenopausal women. METHODS: Participants included 118 outpatients (mean age, 49.9 ± 3.2 years; range, 45-55 years) at a department of gynecology in Japan. Information was collected concerning age, medical history, medications, menstrual status, and history of treatment for climacteric symptoms. Oral symptoms, including xerostomia were evaluated with a 3-point scale. The climacteric symptom checklist for Japanese women and 36-Item Short-Form Health were used to evaluate climacteric symptoms and QOL, respectively. In addition, the volume of unstimulated saliva, oral moisture, salivary α-amylase, chromogranin A, and 17-ß estradiol were measured. RESULTS: Higher age, the total number of medications, psychotropic drug, hormone replacement therapy, treatment for climacteric symptoms, sticky mouth, burning sensation of tongue, dryness of nose and 14 of the 21 climacteric symptoms significantly affected xerostomia. In addition, treatment for climacteric symptoms, fall asleep but often awake at night, headaches and dryness of nose were significantly associated with xerostomia. In conclusion, xerostomia is closely associated to factors such as treatment for climacteric symptoms and certain menopausal symptoms, and it may be related to QOL in perimenopausal women.

Which Factors Affect the Long-Term Survival of Patients With Oral Squamous Cell Carcinoma With Distant Metastasis?

PURPOSE: The development of distant metastases (DMs) in patients with oral squamous cell carcinoma (OSCC) leads to dismal prospects for survival. The present study aimed to identify the risk factors for DM development and long-term survival. PATIENTS AND METHODS: The present study was a retrospective cohort study of patients with OSCC at a single institution. The predictor variables were age, gender, lymph node classification, histologic grade, neck dissection, infiltrative growth pattern (INF), vascular/lymphatic invasion, perineural invasion (PI), extranodal extension, local recurrence, nodal metastasis, DMs, interval to the diagnosis of DMs, and surgery for DMs. The primary outcome variables were the 5-year overall survival (OS) and median survival time (MST), which were estimated using the Kaplan-Meier method. Cox hazard models were used to identify the risk factors for DM development. RESULTS: The cohort included 526 patients; the data from 402 were available for analysis. Of these 402 patients, 37 developed DMs. On multivariate analysis, clinical N1 (cN1)-cN2 (hazard ratio [HR], 3.36), moderate/poor differentiation (HR, 2.51), INFc (HR, 3.27), vascular/lymphatic invasion (HR, 2.95), and PI (HR, 2.17) were independent predictors of DM development. The 5-year OS was 84.6% for the non-DM patients and 9.7% for the DM patients, with a MST of 16.9 months. In those with DMs with cN0, the 5-year OS was 18.2% and the MST was 37.2 months. For those with DMs with cN1-cN2, the 5-year OS was 4.7% and the MST was 12.9 months. In patients with an interval to the DM diagnosis of 10.0 months or longer, the 5-year OS was 20.0% and the MST was 38.6 months. In the patients with an interval to the DM diagnosis of less than 10.0 months, the MST was 11.7 months. The 5-year OS of the patients who had undergone pulmonary metastasectomy was 60.0% and the MST of the nonsurgery group was 16.0 months. CONCLUSIONS: In the patients with DMs, stage cN0 and a late interval to DM diagnosis were associated with long-term survival. Pulmonary metastasectomy could be worth considering to improve survival.

Investigation of Surgical Site Infections and Bacteria Detected Following Neck Dissection in Patients with Oral Cancer.

During dissection for oral cancer, there is a high probability of bacteria indigenous to the oral cavity migrating to the surgical field in the neck due to the opening of new pathways of communication with the oral cavity. The risk of postoperative surgical site infection (SSI) in such patients is high due to malnutrition arising from perioperative eating disorders and dysphagia. Neck infections after neck dissection in oral cancer patients were investigated to elucidate the development of SSIs and their relationship with the results of bacterial culture.A total of 86 patients with oral squamous cell carcinoma who underwent neck dissection between January 2012 and December 2016 were enrolled. Ten factors were selected for investigation: (1) sex; (2) age; (3) primary site; (4) type of dissection; (5) whether or not there was a new pathway of communication between the oral cavity and the neck; (6) operative time; (7) blood loss; (8) number of drainage days; (9) amount of drainage at the time of drain removal; and (10) whether or not there was an SSI. Bacteria isolated from the catheter tip on drain removal were also investigated. Significant differences were observed between patients with and without SSIs (p-0.010) according to the presence of a new pathway of communication between the oral cavity and the neck (p-0.004); operative time (p-0.007); number of drainage days (p-0.029); or the amount of drainage at the time of drain removal. The present results indicate that selecting antibiotics appropriate to each patient and administering perioperative oral care are important in preventing SSIs.

Chewing ability and desaturation during chewing in patients with COPD.

Chewing ability is essential to maintain nutrition status and can be associated with oral conditions, sarcopenia, and lung function in patients with chronic obstructive pulmonary disease (COPD). Herein, our pilot study investigated the chewing ability and degree of desaturation during chewing in patients with COPD (n = 41) and control subjects (n = 22). Subjects chewed a color-changing chewing gum for 1 minute and chewing ability was assessed by the color of the chewed gum, which was scored from 1 (very poor) to 5 (very good). Arterial oxygen saturation (SpO2) was monitored using a pulse oximeter and the difference in SpO2 was determined by comparison between before and during chewing. The mean color score of the chewed gum was lower in the COPD group than in the control group (3.1±0.7 vs 4.2±0.9, p<0.0001). Muscle mass loss (p<0.05), <20 remaining teeth (p<0.005), and COPD (p<0.001) were risk factors for poor chewing ability. The mean SpO2 decreased by 0.78±1.46% during gum chewing for 1 min. The mean SpO2 during gum chewing (95.1±2.4%) was lower than before gum chewing (95.9±1.7%) (p<0.05). The reduction of SpO2 was greater in COPD patients who had fewer remaining teeth (p<0.05). COPD patients with SpO2 reduction >4% during the 6-minute walk test showed greater reduction during gum chewing (p<0.05). Our results suggest that COPD patients with fewer remaining teeth exhibit poor chewing ability and greater desaturation during chewing.

Ten-year Clinical Trends among 575 Consecutive Oral Cancer Patients at Tokyo Dental College Oral Cancer Center.

The facilities comprising Tokyo Dental College (TDC) -the college itself and its medical institutions at Suidobashi, Ichikawa, and Chiba - have been officially recognized as a center for treating oral cancer. The TDC Oral Cancer Center (OCC) was established on April 1, 2006. It provides comprehensive medical care, including that aimed at recovery of postoperative function, such as restoration of stomatognathic function, dysphagia therapy, and placement of maxillary prostheses. The purpose of this study was to investigate patient trends at TDC-OCC over the 10 years following its establishment in order to determine how the safe and high-quality cancer care already provided might be even further improved. Oral cancer patients attending TDC-OCC between April 2007 and March 2017 were investigated. Clinical information was obtained from medical records and analyzed, including that on patient numbers, age, sex, primary site of tumor, clinical stage, and surgery provided. There were 758 new cases, and the number of new cases showed an annual increase. Among the total number of new patients, 575 (75.9%) represented primary cases. The number of operations also showed an increase, which correlated with the increase in the number of patients. The incidence in oral cancer has increased in several countries, including Japan. Oral cancer can be observed macroscopically and touched. In contrast to with cancers at many other sites, and despite various diagnostic devices for early detection having been developed, however, cases are often advanced when first encountered. Many advanced cases were treated at TDC-OCC, and the number of reconstructive operations following progressive cancer also increased over time.

Effectiveness of Communication Studies Program at Tokyo Dental College Based on Comments from Members of Public in Educational Organization.

The purpose of this study was to investigate the effectiveness of the Communication Studies Program at Tokyo Dental College as a tool in behavioral education. The number of Patient Community members who had participated in multiple sets of the program for third-year students in the same year within the 3-year period spanning 2016 to 2018 (152, 148, and 129 students in 2016, 2017, and 2018 respectively), and the period during which they had participated in multiple sets were investigated. Comments on student behavior, including on hairstyle, clothes, and attitude, were also analyzed. The total number of members who had participated in multiple sets (1 set comprised 1 lecture and 2 training sessions) was 5; and their comments were more favorable during the second (sets 3 and 4) than the first half of the 1-month program (sets 1 and 2). During the first half, the students were criticized for speaking softly, having bad posture, not concentrating, and having an attitude inappropriate for a medical worker; but in the second half, they were praised for beginning to adopt the proper attitude for a medical worker, speaking louder, having better posture, and a very serious attitude. These findings suggest that the Communication Studies Program is effective in improving student behavior.

The effects of 2,3-dimercapto-1-propanesulfonic acid (DMPS) and meso-2,3-dimercaptosuccinic acid (DMSA) on the nephrotoxicity in the mouse during repeated cisplatin (CDDP) treatments.

Previously, we reported that specific lower dose of sodium 2,3-dimercapto-1-propanesulfonic acid (DMPS) which is an antidote to heavy metal intoxication, inversely enhanced cisplatin (CDDP)-induced antitumor activity to S-180 cell-bearing mouse. This activity was only weak with meso-2,3-dimercaptosuccinic acid (DMSA), however. This study investigated the effects of lower doses of DMPS or DMSA on the nephrotoxicity and kinetics of CDDP. Kidney and blood isolated from female mice which received CDDP with or without DMPS or DMSA once daily for 4 days were provided for measuring levels of blood urea nitrogen (BUN) and transporter proteins (OCT2: organic cation transporter; MATE1: multidrug and toxin extrusion) mRNA, and CDDP-originated platinum, and TUNEL staining of renal tubular cells. DMPS or DMSA reduced effectively CDDP-induced BUN, and caused a moderate reduction of platinum in kidney. Additionally, both dimercapto-compounds restored the CDDP-reduced mRNA levels of transporter proteins (OCT2 and MATE1), and apparently suppressed the CDDP-induced apoptosis. These results suggest that DMPS, as well as DMSA, at approximate 17-fold dose (µmol/kg) of CDDP, has an enough potential to reverse the CDDP nephrotoxicity, and concomitant use of DMPS considering both dose and timing for administration is potentially useful for preventing nephrotoxicity and enhancing antitumor activity during CDDP chemotherapy.

The association between dental health and nutritional status in chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) and periodontitis are chronic inflammatory systemic diseases with common risk factors (smoking and aging). In COPD, poor periodontal health could result in inadequate nutrition, potentially causing loss of muscle volume. The purpose of this case-control study was to examine our hypothesis that COPD patients have poorer periodontal health and poorer nutritional status than non-COPD patients. Periodontal status was assessed using bleeding on probing (BOP), pocket depth (PD), and plaque-control ratio (PCR). Nutritional status was assessed using body mass index, lean body mass, and serum albumin levels. The COPD group ( n = 60) had fewer remaining teeth, greater BOP, greater PD, and lower serum albumin levels compared with smokers without COPD ( n = 41) and nonsmokers ( n = 35; p < 0.001). COPD was an independent risk factor for poor periodontal health, demonstrated by fewer remaining teeth (relative risk (RR), 5.48; p = 0.0024), BOP (RR, 12.8; p = 0.0009), and having >30% of remaining teeth with a PD ≥ 4 mm (RR, 4.82; p = 0.011). A significant negative correlation existed between the number of teeth with a PD ≥ 4 mm and serum albumin level ( r2 = 0.127; p = 0.013). We demonstrated that poor periodontal health was associated with hypoalbuminemia, suggesting poor nutritional status and inflammation in COPD.

Prenatal Counseling on Prenatal Diagnosis of Cleft Lip and/or Cleft Palate at Tokyo Dental College Ichikawa General Hospital.

Remarkable technological advances have been made in the field of medicine in recent years, one result of which is that a prenatal diagnosis of cleft lip and/or cleft palate (CL/P) is now possible. In this situation, it is extremely important to provide the parents with mental care from the moment they are informed. Here, we describe cases of CL/P treated at our hospital and how such a diagnosis and prenatal counseling are handled. A survey was carried out on 4 cases seen at our department between April 2013 and March 2014. Patients are referred to our department from local or our own obstetrics clinics on a prenatal diagnosis of CL/P based on findings from ultrasonography. If the case is a referral from outside, the patient will first be seen at our own obstetrics department. Our department may then be subsequently requested to provide the parents with prenatal counseling. Effort is made to reassure the parents that postnatal support will be provided, right from the start. Next, the multidisciplinary nature of the treatment process is explained. However, only the essential outline is given at first so as to avoid inducing unnecessary anxiety. A response is also given to any questions the parents may have. Our experience of giving such care leads us to believe that improvements are required in the way that explanations and assistance are provided. The number of cases in which prenatal counseling is required is expected to increase in future.

Odontoblasts as sensory receptors: transient receptor potential channels, pannexin-1, and ionotropic ATP receptors mediate intercellular odontoblast-neuron signal transduction.

Various stimuli induce pain when applied to the surface of exposed dentin. However, the mechanisms underlying dentinal pain remain unclear. We investigated intercellular signal transduction between odontoblasts and trigeminal ganglion (TG) neurons following direct mechanical stimulation of odontoblasts. Mechanical stimulation of single odontoblasts increased the intracellular free calcium concentration ([Ca(2+)]i) by activating the mechanosensitive-transient receptor potential (TRP) channels TRPV1, TRPV2, TRPV4, and TRPA1, but not TRPM8 channels. In cocultures of odontoblasts and TG neurons, increases in [Ca(2+)]i were observed not only in mechanically stimulated odontoblasts, but also in neighboring odontoblasts and TG neurons. These increases in [Ca(2+)]i were abolished in the absence of extracellular Ca(2+) and in the presence of mechanosensitive TRP channel antagonists. A pannexin-1 (ATP-permeable channel) inhibitor and ATP-degrading enzyme abolished the increases in [Ca(2+)]i in neighboring odontoblasts and TG neurons, but not in the stimulated odontoblasts. G-protein-coupled P2Y nucleotide receptor antagonists also inhibited the increases in [Ca(2+)]i. An ionotropic ATP (P2X3) receptor antagonist inhibited the increase in [Ca(2+)]i in neighboring TG neurons, but not in stimulated or neighboring odontoblasts. During mechanical stimulation of single odontoblasts, a connexin-43 blocker did not have any effects on the [Ca(2+)]i responses observed in any of the cells. These results indicate that ATP, released from mechanically stimulated odontoblasts via pannexin-1 in response to TRP channel activation, transmits a signal to P2X3 receptors on TG neurons. We suggest that odontoblasts are sensory receptor cells and that ATP released from odontoblasts functions as a neurotransmitter in the sensory transduction sequence for dentinal pain.

Expression of Cytokeratin 14 and 19 in Process of Oral Carcinogenesis.

Cytokeratins (CK) are abundant in keratinized cells, particularly CK14 and CK19, which are expressed in stratified squamous epithelial cells. In this study, expression of CK14 and 19 was examined in human epithelial and dysplastic tissues. Surgical specimens from patients with clinically diagnosed oral leukoplakia or early cancer were stained with hematoxylin and eosin and classified into normal, low grade dysplasia (LGD), high grade dysplasia (HGD), or squamous cell carcinoma (SCC). The sections were examined by immunostaining and reverse transcription-polymerase chain reaction (RT-PCR) for CK14 and CK19. Expression and the results of RT-PCR for CK14 showed a decrease in the order of LGD, HGD, and SCC, whereas those of CK19 showed an increase in that order. These results suggest that decreased expression of CK14 and increased expression of CK19 serve as indicators of potential for malignant transformation.

Cytokeratin 13, Cytokeratin 17, Ki-67 and p53 Expression in Upper Layers of Epithelial Dysplasia Surrounding Tongue Squamous Cell Carcinoma.

Early detection of oral squamous cell carcinoma (OSCC) improves its prognosis and aids in selecting the appropriate treatment, which may also have a positive effect on quality of life. Early detection, therefore, is an important issue in the treatment of this disease. The purpose of this study was to investigate expression of cytokeratin 13 (CK13), CK17, Ki-67 and p53 as potential markers of tongue SCC. Five areas in 12 specimens were examined: the upper and lower layers of normal epithelium; those of dysplastic epithelial tissue surrounding the cancerous lesion; and the lesion itself. Strong expression of each of the following mRNAs and proteins was observed; CK13 in upper layers of normal epithelium; Ki-67 and p53 in lower layers of normal epithelium; CK13 and CK17 in upper layer of epithelial dysplasia; and CK17, Ki-67, and p53 in lower layer of epithelial dysplasia and cancerous lesions. These results indicate that the characteristic pattern of expression of CK13 and CK17 differs between normal and dysplastic oral epithelium. Oral epithelial dysplasia adjacent to OSCC has high malignant potential, and is similar to early-stage OSCC. This suggests that evaluation of these markers could be a useful secondary procedure for improving detection of early-stage OSCC.

Effects of professional oral health care on reducing the risk of chemotherapy-induced oral mucositis.

PURPOSE: Recent years have seen remarkable progress in cancer therapy, although treatment-induced adverse reactions and complications are not uncommon. Approximately 40 % of patients undergoing chemotherapy for cancer experience adverse reactions in the oral cavity, with nearly half of them developing severe oral mucositis that necessitates postponing therapy and/or changing the drug dosage. The objective of this study was to assess the usefulness of prophylactic professional oral health care (POHC) for preventing mucositis in patients undergoing chemotherapy. METHODS: Twenty-six female patients scheduled for chemotherapy for breast cancer were included in this study and randomized to the self-care or POHC groups. Assessment parameters included oral cavity photographs, plaque control records, Saxon test scores, Oral Assessment Guide scores, and grading using the Common Terminology Criteria for Adverse Events. Beginning before surgery and continuing through the completion of chemotherapy, the POHC patient group received weekly professional oral health care, including scaling, professional cleaning of the tooth surfaces, brushing instructions, and nutritional and lifestyle guidance. RESULTS: More patients in the self-care group developed oral mucositis than in the POHC group. The Oral Assessment Guide score, which was used as an index of oral mucositis, was also significantly lower in the POHC group. Based on the Oral Assessment Guide and plaque control records, there was almost no deterioration of the oral environment in the POHC group, whereas deterioration was observed in the self-care group. CONCLUSIONS: These findings demonstrate the efficacy of regular POHC in reducing the risk of oral mucositis in breast cancer patients undergoing chemotherapy.

Evaluation of superficial oral squamous cell malignancy based on morphometry and immunoexpression of cytokeratin 13 and cytokeratin 17.

OBJECTIVE: Evaluation of combined morphometry and immunoexpression of cytokeratin 13 (CK13) and cytokeratin 17 (CK17) for cytological identification of superficial oral squamous cells. STUDY DESIGN: Smears from 11 tongue squamous cell carcinoma patients were processed by liquid-based cytology, stained via the Papanicolaou method and divided into multiple specimens by cell transfer. Morphometric indices, including nuclear area, nuclear perimeter, nuclear circular rate, largest-to-smallest dimension ratio of the nucleus and nucleocytoplasmic ratio, were measured using a computerized analysis system. CK13 and CK17 were detected by immunostaining. Morphometric values were compared between cell populations with distinct staining and immunoexpression patterns. RESULTS: Most orange G-stained superficial cells were negative for CK13 (99.4%) and CK17 (98.6%). For light green-stained superficial cells, loss of CK13 was associated with greater cellular atypia in the nuclear area, nuclear perimeter and nucleocytoplasmic ratio (p < 0.01), while expression of CK17 was related to higher-grade cellular atypia in the same parameters (p < 0.01) as well as the nuclear circular rate (p < 0.05). CONCLUSION: Immunoexpression of CK13 and CK17 in light green-stained superficial cells was associated with more severe morphological atypia. Combined morphometry and immunoexpression of CK13 and CK17 might be useful for cytological diagnosis of this cell population.

Career paths and aspirations among postgraduate dental trainees on completion of clinical residency program at Tokyo Dental College.

Career paths and aspirations were investigated among postgraduate dental trainees on completion of clinical training at Tokyo Dental College between 2006, when clinical residency became mandatory, and 2011. Overall, those finding employment with independent general dental practitioners accounted for the majority (34%), followed by those entering postgraduate courses at the Chiba Hospital (20%), those embarking on a postgraduate clinical specialty course at the Chiba Hospital (16%), and those going on to other universities (7%). At the Chiba Hospital, the number selecting postgraduate courses, residency training (including further residency training or a postgraduate clinical specialty course), or employment with a general dental practitioner was almost the same; however, the number selecting postgraduate courses at the Suidobashi Hospital was low, showing a strong tendency toward becoming a general or clinical practitioner. At the Ichikawa General Hospital, most of the trainees decided to remain at the same school or hospital as postgraduate students or residents, showing an aspiration toward further specialization. The results of the Fisher's exact test showed a significant difference in career paths between the Chiba, Suidobashi, and Ichikawa General Hospitals. Trends among postgraduate dental trainees from this and other schools completing the clinical residency program here and subsequently entering postgraduate courses, further residency training, or a postgraduate clinical specialty course at this school were investigated. No major difference was observed in the percentage of trainees remaining at the same school or entering postgraduate courses between those from this and those from other schools; however, more trainees from other schools selected further residency training, while fewer selected a postgraduate clinical specialty course.