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Background: Western guidelines often recommend biguanides as the first-line treatment for diabetes. However, dipeptidyl peptidase-4 (DPP-4) inhibitors, alongside biguanides, are increasingly used as the first-line therapy for type 2 diabetes (T2DM) in Japan. However, there have been few studies comparing the effectiveness of biguanides and DPP-4 inhibitors with respect to diabetes-related complications and cardio-cerebrovascular events over the long term, as well as the costs associated. Objective: We aimed to compare the outcomes of patients with T2DM who initiate treatment with a biguanide versus a DPP-4 inhibitor and the long-term costs associated. Methods: We performed a cohort study between 2012 and 2021 using a new-user design and the Shizuoka Kokuho database. Patients were included if they were diagnosed with T2DM. The primary outcome was the incidence of cardio-cerebrovascular events or mortality from the initial month of treatment; and the secondary outcomes were the incidences of related complications (nephropathy, renal failure, retinopathy, and peripheral neuropathy) and the daily cost of the drugs used. Individuals who had experienced prior events during the preceding year were excluded, and events within 6 months of the start of the study period were censored. Propensity score matching was performed to compare between two groups. Results: The matched 1:5 cohort comprised 529 and 2,116 patients who were initially treated with a biguanide or a DPP-4 inhibitor, respectively. Although there were no significant differences in the incidence of cardio-cerebrovascular events or mortality and T2DM-related complications between the two groups (p = 0.139 and p = 0.595), daily biguanide administration was significantly cheaper (mean daily cost for biguanides, 61.1 JPY; for DPP-4 inhibitors, 122.7 JPY; p<0.001). Conclusion: In patients with T2DM who initiate pharmacotherapy, there were no differences in the long-term incidences of cardio-cerebrovascular events or complications associated with biguanide or DPP-4 use, but the former was less costly. [ABSTRACT FROM AUTHOR]

Use of statins for primary prevention can reduce all-cause mortality in Asian elderly populations, but their effect and the specific effective subgroups in the elderly Japanese population remain unclear. This study examined the relationship between statin therapy for primary prevention and mortality reduction in older Japanese adults, and investigated the effective subgroups. The cohort study was conducted using the Shizuoka Kokuho Database (SKDB). Data were compared between the statin-treated group and a non-statin-treated (control) group using the inverse probability of treatment weighting (IPTW) method. In the SKDB cohort aged ≥65 years, new statin use was associated with a decreased risk of all-cause mortality (hazard ratio, 0.40; 95% confidence interval [CI], 0.33–0.48) after IPTW adjustment. The risk difference for mortality at 5 years in the statin-treated group compared with that in the control group was 0.05 (95% CI, 0.04–0.06), and the number needed to treat was 21.20 (95% CI, 18.10–24.70). In conclusion, statin use for primary prevention in older adults may reduce the risk of all-cause mortality in the population without atherosclerotic disease. Furthermore, statin use for primary prevention is feasible in patients aged 75 to <85 years and in patients with comorbidities such as diabetes, or dementia. [ABSTRACT FROM AUTHOR]

Background: Long-term cancer prognosis after initial surgical procedures is an unlikely endpoint for clinical trials. Medical claim databases may aid in addressing this issue regardless of limited information on disease and patient background. However, the long-term prognosis (especially regarding long-term care needs) following surgical procedures remains unclear. This study aimed to assess whether long-term outcomes, such as the exacerbation of long-term care needs and mortality, differ with surgical methods. Methods: Using a longitudinal study with linkage between medical claim and long-term care database, patients with primary colorectal cancer who underwent initial colonoscopies were identified through anonymized data in Japan (Shizuoka Kokuho Database, 2012–2018). Odds ratios (ORs) for long-term outcomes (long-term care needs and all-cause mortality during a 6.5-year follow-up period) were analyzed using logistic regression to compare laparoscopy and endoscopic surgery to laparotomy. Results: Overall, 3,744 primary colorectal cancer cases (822 laparotomies, 705 laparoscopies, and 2,217 endoscopic surgeries) were included. Compared to the laparotomy group, the crude OR for exacerbation of long-term care needs in the laparoscopic surgery group was 0.376 (95% confidence interval, 0.227, 0.624), while the OR for all-cause mortality was 0.22 (0.329, 0.532). Conclusion: This is the first study to analyze long-term prognosis after surgery for patients with colorectal cancer to combine medical and long-term needs data. As the national health insurance claim database rarely includes information on cancer stage and comorbidities, better prognosis on endoscopic surgery may need careful interpretation. Therefore, laparoscopy has superior outcomes in terms of long-term care needs and mortality compared to those of laparotomy. [ABSTRACT FROM AUTHOR]

Outpatient nutritional counseling by a registered dietitian is often performed to prevent weight loss, but evidence supporting this practice is insufficient. In this study, we aimed to clarify the effectiveness of four-time outpatient nutritional counseling in weight-loss prevention compared with conventional intervention limited to one-time nutritional counseling. This study was designed as a retrospective cohort study. The target population was postoperative patients with stage IA and IB gastric cancer. Groups that received one-time and four-time nutritional counseling included patients who underwent gastrectomy from May 2014 to April 2017 and May 2017 to December 2019, respectively. The one-time group received counseling at discharge; the four-time group received counseling at discharge, at the first outpatient visit, and at 3 and 6 months postoperatively. There were 58 patients in the one-time group and 27 patients in the four-time group, with a significant difference in length of hospital stay (p = 0.042). Thirty-six patients (62.1%) in the one-time nutritional counseling group and 12 (44.4%) in the four-time group had a weight loss of 5% or more from hospital discharge to 6 months postoperatively. The adjusted risk ratio for the effectiveness of four counseling sessions compared with one session was 0.69 (95% confidence interval 0.35–1.34). In subgroup analysis, the effect of nutritional guidance was greater for patients with body mass index ≥23 kg/m2, but this depended on the outcome and number of cases, and there was no essential difference between the groups. In postoperative patients with stage IA and stage IB gastric cancer, four sessions of outpatient nutrition counseling may be not superior to one counseling session in preventing weight loss. [ABSTRACT FROM AUTHOR]

Sleep drugs are often necessary to treat insomnia in older patients. Benzodiazepine receptor agonists (BZRAs) are primarily used for insomnia in these patients, but there are concerns regarding their association with delirium and bone fractures. Among sleep drugs, orexin receptor antagonists such as suvorexant have a lower risk of delirium than BZRAs, but their effectiveness in preventing hip fractures is unknown. Hip fracture is a life-threatening trauma in advanced-age patients and a social problem. Therefore, we investigated the relationship between suvorexant and hip fracture. The Shizuoka Kokuho Database was used to compare the time to hip fracture in patients who had been newly taking suvorexant and other sleep drugs such as benzodiazepines since November 2014. A proportional hazards model for hip fracture as an outcome was used to estimate the hazard ratio. Propensity scores were estimated using a logistic regression model, and the confounding factors were age, sex, several comorbidities, and each oral medication. The suvorexant group comprised 6860 patients (110 with hip fracture), and the BZRA group (benzodiazepines and Z-drugs) comprised 50,203 patients (1487 with hip fracture). In the matched cohort (6855:6855 patients), 259 and 249 patients in the suvorexant and BZRA group developed hip fractures during the observational period, respectively. The hazard ratio of the suvorexant group compared with the BZRA group was 1.48 (95% confidence interval, 1.20–1.82). In the subgroup analysis, patients in the suvorexant group had a higher risk of hip fracture if they were aged >75 years, had no diabetes, had no neurological disease, had no renal failure, had liver disease, had hypertension, were not taking alpha 1 blockers, and were not taking oral steroids. Among people in the Japanese regional population who use sleep drugs, patients taking suvorexant can be at higher risk of hip fracture than patients taking BZRAs. [ABSTRACT FROM AUTHOR]

In the research literature on factors associated with gallstones, large population-based cohort studies are rare. We carried out a study of this type to explore risk factors for the onset of gallstones. This study included Japanese participants aged 40–107 years who were followed prospectively from January 2012 to September 2020 using a dataset composed of two individually linked databases, one containing annual health checkup records and the other containing medical claims for beneficiaries of the National Health Insurance System and the Medical Care System for Elderly in the Latter Stage of Life in Shizuoka Prefecture, Japan. Among the 611,930 participants in the analysis set, 23,843 (3.9%) were diagnosed with gallstones during the observational period (median [max]: 5.68 [7.5] years). Multivariate analysis revealed that risk of gallstone disease was increased by male sex, cerebrovascular disease, any malignancy, dementia, rheumatic disease, chronic pulmonary disease, hypertension, and H. pylori-infected gastritis. These findings provide essential insights into the etiology of cholelithiasis and may contribute to efforts to reduce the incidence of the disease. [ABSTRACT FROM AUTHOR]

Aim: Bedriddenness Rank (BR) and Cognitive Function Score (CFS), issued by the Ministry of Health, Labour and Welfare, Japan, are easy-to-use and widely used in the medical and long-term care insurance systems in Japan. This study aims to clarify the criterion-related validity of the CFS with the Mini-Mental State Examination (MMSE) and ABC Dementia Scale (ABC-DS), and to re-evaluate the criterion-related validity of BR with the Barthel Index (BI) or Katz Index (KI) in more appropriate settings and a larger population compared with the previous study. Methods: A single-center prospective observational study was conducted in an acute care hospital in a suburban city in Japan. All inpatients aged 20 years or older admitted from October 1, 2018 to September 30, 2019. The relationship between BR and the BI and KI, and the relationship between CFS and the MMSE and ABC-DS were analyzed using Spearman's correlation coefficients. Results: We enrolled 3,003 patients. Of these, 1,664 (56%) patients exhibited normal BR. The median (interquartile range) values of the BI and KI were 100 (65–100) and 6 (2–6), respectively. Spearman's rank correlation coefficients between BR and the BI and KI were −0.891 (p < 0.001) and −0.877 (p < 0.001), respectively. Of the patients, 1,967 (65.5%) showed normal CFS. The median (interquartile range) MMSE of 951 patients with abnormal CFS and ABC-DS of all patients were 15 (2–21) and 117 (102–117), respectively. Spearman's rank correlation coefficients between CFS and MMSE and ABC-DS were −0.546 (p < 0.001) and −0.862 (p < 0.001), respectively. Conclusions: BR and CFS showed significant criterion-related validity with well-established but complicated objective scales for assessing activities of daily living and cognitive functions, respectively. These two scales, which are easy to assess, are reliable and useful in busy clinical practice or large-scale screening settings. [ABSTRACT FROM AUTHOR]

Background: Vitamin D deficiency (VDD) is associated with an increased risk for lifestyle-related diseases. In Japan, VDD is quite prevalent in all age groups, with its high risk in young women. Furthermore, its association during pregnancy with gestational hypertension and low birth weight has also been reported. VDD can be diagnosed by serum 25-hydroxyvitamin D [25(OH)D] levels, which, however, is not suited for screening. Therefore, we will create a predictive model for serum 25(OH)D concentration and prevalence of VDD based on such data as region, sun exposure habit, and vitamin D intake in young women. Methods: From 2020 to 2022, we conduct a cross-sectional study of 600 young women in four regions of Japan, identify the indices associated with serum 25(OH)D concentrations such as sun exposure habits, habitual vitamin D intake, ultraviolet-B irradiation, seasons (summer and winter) and latitude, and construct prediction models for serum 25(OH)D concentrations and VDD risk. This study has been registered with UMIN-CTR (ID: UMIN000041527). Results: One hundred and fifteen subjects have been collected from 6 institutions in winter as of May 2021. When data from more than 200 subjects have become available, we will conduct the interim analysis, summarize the data by region and facility, review the inclusion criteria for analysis, and check for missing values and outliers. Prediction models for serum 25(OH)D concentration and VDD will be determined in the final analysis when all cases have been collected. Conclusions: A screening tool for VDD risk to be developed in our study based on the predictive model would help the public and medical professionals prevent lifestyle-related diseases through improving VDD. Additionally, the results may serve as the scientific basis for determining the appropriate vitamin D intake and sun exposure standards. [ABSTRACT FROM AUTHOR]

Determining values of plasma renin activity (PRA) or plasma active renin concentration (ARC), plasma aldosterone concentration (PAC), and aldosterone-to-renin ratio (ARR) is essential to diagnose primary aldosteronism (PA), but it takes several days with conventional radioimmunoassays (RIAs). Chemiluminescent enzyme immunoassays for PAC and ARC using the Accuraseed® immunoanalyzer facilitated the determination, but relations between Accuraseed® immunoanalyzer-based and RIA-based values in samples of PA confirmatory tests and adrenal venous sampling remained to be elucidated. We addressed this issue in the present study. This is a prospective, cross-sectional study. ARC and PAC values were measured by the Accuraseed® immunoanalyzer in samples, in which PRA and PAC values had been measured by the PRA-FR® RIA and SPAC®-S Aldosterone kits, respectively. The relations between Accuraseed® immunoanalyzer-based and RIA-based values were investigated with regression analyses. The optimal cutoff of Accuraseed® immunoanalyzer-based ARR for PA screening was determined by the receiver operating characteristic analysis. After log-log transformations, linear relations with high coefficients of determination were observed between Accuraseed® immunoanalyzer-based and RIA-based data of renin and aldosterone. Following the PA guidelines of Japan Endocrine Society, Accuraseed® immunoanalyzer-based cutoffs were calculated from the regression equations: the basal PAC for PA screening >12 ng/dL, PAC for the saline infusion test >8.2 ng/dL, ARC for the furosemide-upright test <15 pg/mL, and ARR for the captopril challenge test >3.09 ng/dL per pg/mL. The optimal cutoff of Accuraseed® immunoanalyzer-based ARR for PA screening was >2.43 ng/dL over pg/mL not to overlook bilateral PA patients. The present study provided conversion formulas between Accuraseed® immunoanalyzer-based and RIA-based values of renin, aldosterone, and ARR, not only in basal samples but also in samples of PA confirmatory tests and adrenal venous sampling. Although validation studies are awaited, the present study will become priming water of harmonization of renin and aldosterone immunoassays. [ABSTRACT FROM AUTHOR]

Objectives: Dry socket and post-extraction pain are typical discomforts experienced by patients after tooth extraction. In this study, we inserted gauze coated with oxytetracycline-hydrocortisone ointment into the extraction socket immediately after lower third molar extraction and then evaluated the occurrence of dry socket and post-extraction pain compared with gauze non-insertion. Methods: This retrospective study was carried out on patients undergoing lower third molar extraction in the Department of Oral Surgery at Shizuoka Prefectural General Hospital in Shizuoka, Japan from November 2018 to October 2019. A comparison was carried out between a gauze-insertion group and a non-insertion group. The occurrence versus non-occurrence of dry socket was determined, and degree of pain was assessed based on a visual analogue scale (VAS) and on patients reporting the number of loxoprofen sodium oral analgesic tablets (60mg/tablet) that they had taken. Dry socket was defined as patient-reported spontaneous pain that did not subside 1 to 3 days postoperatively. Spontaneous post-extraction pain was recorded four times: on the operative day, on the first postoperative day (POD1), on POD3, and during suture removal (POD7). Results: The occurrence of dry socket was lower in the gauze-insertion group than in the non-insertion group (0.9%, 2/215 vs. 19.6%, 9/46, p<0.001). The results also showed that both VAS-defined pain level and the number of analgesic tablets taken were lower in the gauze-insertion group than in the non-insertion group on POD3 and POD7. Conclusions and clinical relevance: Inserting gauze coated with oxytetracycline-hydrocortisone ointment into the extraction socket immediately after third molar extraction reduces the occurrence of both dry socket and post-extraction pain. [ABSTRACT FROM AUTHOR]

Aim: Most predictive models for falls developed previously were awkward to use because of their complexity. We developed and validated a new easier-to-use predictive model for falls of adult inpatients using easily accessible information including the public ADL scale in Japan. Methods: We retrospectively analyzed data from Japanese adult inpatients in an acute care hospital from 2012 to 2015. Two-thirds of cases were randomly extracted to the test set and one-third to the validation set. Data including age, sex, activity of daily living (ADL), public scales in Japan of ADL "bedriddenness rank," and cognitive function in daily living, hypnotic medications, previous falls, and emergency admission were derived from hospital records. Falls during hospitalization were identified from incident reports. Two predictive models were created by multivariate analysis, each of which was assessed by area under the curve (AUC) from the validation set. Results: A total of 7,858 adult participants were available. The AUC of model 1, using 13 factors—age, sex (male), emergency admission, use of ambulance, referral letter, admission to Neurosurgery, admission to Internal Medicine, use of hypnotic medication, permanent damage by stroke, history of falls, visual impairment, independence of eating, and bedriddenness rank—with low mutual collinearity and showing significant relationship by multivariate logistic regression analysis, was 0.789 in the validation set. The AUC of parsimonious model 2, using age and seven factors—sex (male), emergency admission, admission to Neurosurgery, use of hypnotic medication, history of falls, independence of eating, and bedriddenness rank—showing statistical significance by multivariate analysis in model 1, was 0.787 in the validation set. Conclusions: We proposed new predictive models for inpatients' fall using the public ADL scales in Japan, which had a higher degree of usability because of their use of simpler and fewer (8 or 13) predictors, especially parsimonious model 2. [ABSTRACT FROM AUTHOR]

It is difficult to determine whether or not end-of-life care is necessary for frail older adults complaining of anorexia without underlying disease, such as cancer or organ failure. The main reason for this is the lack of the specification of the anorexia cause and no understanding of the cause-providing factor and the prognostic factor. This study aimed to clarify the cause of anorexia, and the determinant of the cause and recovery from anorexia. Retrospective chart reviews were conducted on patients with anorexia without an underlying disease who were aged ≥65 years and visited the emergency department of a single tertiary care center between 2016 and 2017. Patient characteristics at hospital visit, the cause of anorexia, and diagnostic modalities were summarized. The diagnosis-providing rate, recovery rate, and the association between them were analyzed. Eighty-three patients (mean age 82.3 years; 50.6% male) were investigated. In 67 patients (81%), the causes of anorexia were identified, including 18 patients (22%) with infection, 13 (16%) with benign gastrointestinal diseases, and 7 (8%) with cardiovascular diseases. In 16 patients (19%), the causes of anorexia were not identified despite examinations. The modality that most contributed to diagnosis was plain computed tomography followed by blood tests. The value regarding information in history-taking and physical examinations was limited. Sixty-five patients (78%) recovered. Only 73% of patients with a definite cause recovered; all patients with an unknown cause recovered. Older adults with anorexia are not always at the end of life, and efforts to identify the cause are crucial. Moreover, it is vital to realize the limitations associated with the treatment of infections and cardiovascular diseases. [ABSTRACT FROM AUTHOR]

Background: The aging of populations is rapidly accelerating worldwide. Especially, Japan has maintained the highest rate of population aging worldwide. As countermeasures, the Japanese government prioritized the promotion of local comprehensive care systems and collaboration in medical care and social (long-term) care. Development of a system to connect medical and social services in the community is necessary for the increasing older people, especially for the people in the stage of end of life. Objective: This study aimed to assess the effect of a multidisciplinary end-of-life educational intervention program on confidence in inter-professional collaboration and job satisfaction among health and social care professionals. Design: a cluster-randomized controlled trial Setting/Participants: Three professional groups (home care nurses, care managers, and heads of care workers) in an urban area participated in this trial. Intervention: We implemented a multidisciplinary end-of-life educational intervention program comprising two educational workshops and an educational booklet to support multidisciplinary care for end-of-life patients during the 7-month study period. Main outcome measure: Confidence in improved interactions among professionals and job satisfaction were assessed with the Face-to-Face Cooperative Confidence Questionnaire and the Minnesota Satisfaction Questionnaire at T1 (before intervention) and T2 (7 months after the intervention). Results: In total, 291 professionals participated in this study (experimental group n = 156; control group n = 135). Multivariate regression analyses showed significant between-group increases on all of seven subscales in participants’ face-to-face cooperative confidence over the study period; no effect was evident regarding job satisfaction. Conclusions: A multidisciplinary end-of-life educational intervention program increased confidence in multidisciplinary collaboration among health and social care professionals. Trial number: UMIN Clinical Trial Registry, Japan . [ABSTRACT FROM AUTHOR]

Background: Chemoradiotherapy (CRT) has improved organ preservation or overall survival (OS) of locoregionally advanced head and neck squamous cell cancer (LAHNSCC), but in clinical trials of conventional CRT, increasing CRT intensity has not been shown to improve OS. In the Adjuvant ChemoTherapy with S-1 after curative treatment in patients with Head and Neck Cancer (ACTS-HNC) phase III study, OS of curative locoregional treatments improved more with adjuvant chemotherapy with S-1 (tegafur gimeracil oteracil potassium) than with tegafur/uracil (UFT). ACTS HNC study showed the significant efficacy of S-1 after curative radiotherapy in sub-analysis. We explored the efficacy of S-1 after curative CRT in a subset of patients from the ACTS-HNC study. Methods: Patients with stage III, IVA, or IVB LAHNSCC were enrolled in this study to evaluate the efficacy of S-1 compared with UFT as adjuvant chemotherapy after curative CRT in the ACTS-HNC study. Patients received S-1 at 80–120 mg/day in two divided doses for 2 weeks, followed by a 1-week rest, or UFT 300 or 400 mg/day in two or three divided doses daily, for 1 year. The endpoints were OS, disease-free survival, locoregional relapse-free survival, distant metastasis-free survival (DMFS), and post-locoregional relapse survival. Results: One hundred eighty patients (S-1, n = 87; UFT, n = 93) were included in this study. Clinical characteristics of the S-1 and UFT arms were similar. S-1 after CRT significantly improved OS (hazard ratio [HR], 0.46; 95% confidence interval [CI], 0.22–0.93) and DMFS (HR, 0.50; 95% CI, 0.26–0.97) compared with UFT. Conclusion: As adjuvant chemotherapy, S-1 demonstrated better efficacy for OS and DMFS than UFT in patients with LAHNSCC after curative CRT and may be considered a treatment option following curative CRT. For this study was not preplanned in the ACTS-HNC study, the results is hypothesis generating but not definitive. [ABSTRACT FROM AUTHOR]

Regional demographics of spinal cord injuries (SCIs) are fundamental to identifying and implementing appropriate preventive measures. The current study was conducted as a longitudinal analysis of all patients with SCIs admitted to the Hyogo Rehabilitation Center over a 19-year period. The sex and age of the patient, time and nature of injury (i.e., cause, level, and extent), and period from injury to admission were evaluated retrospectively. Pertinent tests, including Poisson regression analysis, and the Cochran–Armitage, Kruskal–Wallis, and chi-square tests, were applied to assess demographic variables, with statistical significance set at p < 0.05. Between 1995 and 2013, a total of 632 patients with SCIs (predominantly male and largely < 60 years old) were admitted to our center for rehabilitation. Although the male: female ratio remained unchanged throughout the study period, the ratio of older adults increased over time. In assessing the cause of injury, the majority of the patients involved in road traffic accidents were aged ≤ 44 years, whereas patients aged ≥ 45 years accounted for the majority of low-distance falls and disease-related SCIs, the proportions of which gradually increased. Complete paralysis and paraplegia primarily occurred in patients aged ≤ 44 years, whereas the majority of incomplete injuries and tetraplegia were limited to those aged ≥ 45 years. The patient age at the time of SCI and the nature of the injury sustained were interrelated. Age-specific strategies thus offered the best means of preventing/reducing the incidence of SCIs in Hyogo prefecture. [ABSTRACT FROM AUTHOR]

Background: The number of elderly patients with maxillofacial trauma is rapidly increasing due to active lifestyles and longevity. Shimane prefecture has the fastest growing proportion of elderly individuals in Japan. The aim of this study was to reveal the distinctive features and treatment modes of mandibular fracture treatment mode in patients requiring hospitalization at the Department of Oral and Maxillofacial Surgery, Shimane University Hospital, Japan. Patients and Methods: Patient age, sex, period between injury and first consultation, years since injury, cause of injury, fracture site, treatment, and duration of hospitalization were evaluated. Univariate Poisson regression, relative risk with 95% confidence interval based on the Wald test, Fisher’s exact test, and Kruskal-Wallis test were used to explore associations among clinical and demographic variables. Results: In total, 305 patients were diagnosed with and hospitalized for mandibular fracture from 1980 to 2010. Younger age increased the risk for mandibular fracture. Incidence was higher in males than females, particularly in the young, but the male to female ratio decreased with age. The period until first hospital consultation decreased progressively over the study period. Fall was a much more frequent cause in patients aged ≥60 than in those aged <60 years. Mandibular fracture with condyle, symphysis, and angle involvement were most common and were associated with sex, age, and treatment mode. Length of hospitalization has decreased since 1980. Conclusion: In our department, patients aged ≥60 years accounted for a greater proportion of mandibular fracture cases than in many previous studies, reflecting the greater proportion of elderly residents in Shimane prefecture. [ABSTRACT FROM AUTHOR]

Background: Oral epithelial dysplasia (OED) and carcinoma in situ (CIS) are defined by dysplastic cells in the epithelium. Over a third of oral squamous cell carcinoma (OSCC) patients present with associated OED. However, accurate histopathological diagnosis of such lesions is difficult. Nucleus accumbens-associated protein 1 (NAC1) is a member of the Pox virus and Zinc finger/Bric-a-brac Tramtrack Broad complex family of proteins, and is overexpressed in OSCC. This study aimed to determine whether NAC1 has the potential to be used as a marker to distinguish OED and OSCC. Methods and Findings: The study included 114 patients (64 men, 50 women). There were 67, 10, and 37 patients with OED, CIS, and OSCC, respectively. NAC1 labeling indices (LIs) and immunoreactivity intensities (IRI) were evaluated. The patients’ pathological classification was significantly associated with age, sex, NAC1 LIs, and NAC1 IRI (p = 0.025, p = 0.022, p < 0.001, and p < 0.001, respectively). As a result of multivariate analysis, a predictive model was made; this identified the NAC1 LIs (OR [95% CI] 1.18 [1.11–1.28], p < 0.001) and NAC1 IRI (0.78 [0.68–0.86], p < 0.001) as predictive factors for CIS/OSCC. The NAC1 LIs/IRI cut-off values which discriminated between OED and CIS/OSCC were 50%/124 pixels. For NAC1 LIs with > 50% positivity the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were 0.766, 0.910, 0.857, and 0.847, respectively. For NAC1 IRI with ≤ 124 positive pixels, the sensitivity, specificity, PPV, and NPV were 0.787, 0.866, 0.804, and 0.853, respectively. Though there are several potential limitations to this study and the results were obtained from a retrospective analysis of a single site cohort, the data suggest that the NAC1 LIs/IRI is a strong predictor of CIS/OSCC. Conclusions: NAC1 has potential as a marker for distinguishing OED from CIS/OSCC. [ABSTRACT FROM AUTHOR]

Background: We previously reported the utility of preoperative nuclear morphometry for evaluating risk for cervical lymph node metastases in tongue squamous cell carcinoma. The risk for lymph node metastasis in oral squamous cell carcinoma, however, is known to differ depending on the anatomical site of the primary tumor, such as the tongue, gingiva, mouth floor, and buccal mucosa. In this study, we evaluated the applicability of this morphometric technique to evaluating the risk for cervical lymph node metastasis in oral squamous cell carcinoma., Methods: A digital image system was used to measure the mean nuclear area, mean nuclear perimeter, nuclear circular rate, ratio of nuclear length to width (aspect ratio), and nuclear area coefficient of variation (NACV). Relationships between these parameters and nodal status were evaluated by t-test and logistic regression analysis., Results: Eighty-eight cases of squamous cell carcinoma (52 of the tongue, 25 of the gingiva, 4 of the buccal mucosa, and 7 of the mouth floor) were included: 46 with positive node classification and 42 with negative node classification. Nuclear area and perimeter were significantly larger in node-positive cases than in node-negative cases; however, there were no significant differences in circular rate, aspect ratio, or NACV. We derived two risk models based on the results of multivariate analysis: Model 1, which identified age and mean nuclear area and Model 2, which identified age and mean nuclear perimeter. It should be noted that primary tumor site was not associated the pN-positive status. There were no significant differences in pathological nodal status by aspect ratio, NACV, or primary tumor site., Conclusion: Our method of preoperative nuclear morphometry may contribute valuable information to evaluations of the risk for lymph node metastasis in oral squamous cell carcinoma.