Deep learning-based vessel automatic recognition for laparoscopic right hemicolectomy.

BACKGROUND: In laparoscopic right hemicolectomy (RHC) for right-sided colon cancer, accurate recognition of the vascular anatomy is required for appropriate lymph node harvesting and safe operative procedures. We aimed to develop a deep learning model that enables the automatic recognition and visualization of major blood vessels in laparoscopic RHC. MATERIALS AND METHODS: This was a single-institution retrospective feasibility study. Semantic segmentation of three vessel areas, including the superior mesenteric vein (SMV), ileocolic artery (ICA), and ileocolic vein (ICV), was performed using the developed deep learning model. The Dice coefficient, recall, and precision were utilized as evaluation metrics to quantify the model performance after fivefold cross-validation. The model was further qualitatively appraised by 13 surgeons, based on a grading rubric to assess its potential for clinical application. RESULTS: In total, 2624 images were extracted from 104 laparoscopic colectomy for right-sided colon cancer videos, and the pixels corresponding to the SMV, ICA, and ICV were manually annotated and utilized as training data. SMV recognition was the most accurate, with all three evaluation metrics having values above 0.75, whereas the recognition accuracy of ICA and ICV ranged from 0.53 to 0.57 for the three evaluation metrics. Additionally, all 13 surgeons gave acceptable ratings for the possibility of clinical application in rubric-based quantitative evaluations. CONCLUSION: We developed a DL-based vessel segmentation model capable of achieving feasible identification and visualization of major blood vessels in association with RHC. This model may be used by surgeons to accomplish reliable navigation of vessel visualization.

Machine learning-based Automatic Evaluation of Tissue Handling Skills in Laparoscopic Colorectal Surgery: A Retrospective Experimental Study.

OBJECTIVE: To develop a machine learning model that automatically quantifies the spread of blood in the surgical field using intraoperative videos of laparoscopic colorectal surgery and evaluate whether the index measured with the developed model can be used to assess tissue handling skill. BACKGROUND: Although skill evaluation is crucial in laparoscopic surgery, existing evaluation systems suffer from evaluator subjectivity and are labor-intensive. Therefore, automatic evaluation using machine learning is potentially useful. MATERIALS AND METHODS: In this retrospective experimental study, we used training data with annotated labels of blood or non-blood pixels on intraoperative images to develop a machine learning model to classify pixel RGB values into blood and non-blood. The blood pixel count per frame (the total number of blood pixels throughout a surgery divided by the number of frames) was compared among groups of surgeons with different tissue handling skills. RESULTS: The overall accuracy of the machine learning model for the blood classification task was 85.7%. The high tissue handling skill group had the lowest blood pixel count per frame, and the novice surgeon group had the highest count (mean [SD]: high tissue handling skill group 20972.23 [19287.05] vs. low tissue handling skill group 34473.42 [28144.29] vs. novice surgeon group 50630.04 [42427.76], P <0.01). The difference between any 2 groups was significant. CONCLUSIONS: We developed a machine learning model to measure blood pixels in laparoscopic colorectal surgery images using RGB information. The blood pixel count per frame measured with this model significantly correlated with surgeons' tissue handling skills.

Universal meta-competencies of operative performances: a literature review and qualitative synthesis.

BACKGROUND: Prioritizing patient health is essential, and given the risk of mortality, surgical techniques should be objectively evaluated. However, there is no comprehensive cross-disciplinary system that evaluates skills across all aspects among surgeons of varying levels. Therefore, this study aimed to uncover universal surgical competencies by decomposing and reconstructing specific descriptions in operative performance assessment tools, as the basis of building automated evaluation system using computer vision and machine learning-based analysis. METHODS: The study participants were primarily expert surgeons in the gastrointestinal surgery field and the methodology comprised data collection, thematic analysis, and validation. For the data collection, participants identified global operative performance assessment tools according to detailed inclusion and exclusion criteria. Thereafter, thematic analysis was used to conduct detailed analyses of the descriptions in the tools where specific rules were coded, integrated, and discussed to obtain high-level concepts, namely, "Skill meta-competencies." "Skill meta-competencies" was recategorized for data validation and reliability assurance. Nine assessment tools were selected based on participant criteria. RESULTS: In total, 189 types of skill performances were extracted from the nine tool descriptions and organized into the following five competencies: (1) Tissue handling, (2) Psychomotor skill, (3) Efficiency, (4) Dissection quality, and (5) Exposure quality. The evolutionary importance of these competences' different evaluation targets and purpose over time were assessed; the results showed relatively high reliability, indicating that the categorization was reproducible. The inclusion of basic (tissue handling, psychomotor skill, and efficiency) and advanced (dissection quality and exposure quality) skills in these competencies enhanced the tools' comprehensiveness. CONCLUSIONS: The competencies identified to help surgeons formalize and implement tacit knowledge of operative performance are highly reproducible. These results can be used to form the basis of an automated skill evaluation system and help surgeons improve the provision of care and training, consequently, improving patient prognosis.

Evaluation of oral brush liquid-based cytology for oral squamous cell carcinoma: a comparative study of cytological and histological diagnoses at a single center.

PURPOSE: Liquid-based cytology is highly useful in oral cytology. However, there are only few reports on the accuracy of this method. The current study aimed to compare oral liquid-based cytological and histological diagnoses and to evaluate items that should be considered in oral cytological diagnosis for oral squamous cell carcinoma. METHODS: We included 653 patients who underwent both oral cytological and histological examinations. Data on sex, specimen collection region, cytological and histological diagnoses, and histological images were reviewed. RESULTS: The overall male-to-female ratio was 1:1.18. The tongue was the most common specimen collection region, followed by the gingiva and buccal mucosa. The most common cytological examination result was negative (66.8%), followed by doubtful (22.7%) and positive (10.3%). The sensitivity, specificity, positive predictive value, and negative predictive value of cytological diagnosis were 69%, 75%, 38%, and 92%, respectively. Approximately 8.3% of patients with a negative cytological diagnosis had a histological diagnosis of oral squamous cell carcinoma. Furthermore, 86.1% of histopathologic images of cytology-negative squamous cell carcinomas exhibited well-differentiated keratinocytes lacking atypia on the surface. The remaining patients developed recurrence, or they had low cell counts. CONCLUSION: Liquid-based cytology is useful in screening oral cancer. However, a cytological diagnosis of superficial-differentiated oral squamous cell carcinoma is occasionally inconsistent with the histological diagnosis. Therefore, histological and cytological examinations should be performed if tumor-like lesions are suspected clinically.

[Hypokalemia and potassium replacement therapy in allogeneic hematopoietic stem cell transplantation].

Hypokalemia is common in allogeneic hematopoietic stem cell transplantation (allo-HCT) patients and is associated with non-relapse mortality (NRM). Therefore, it is extremely important to replace potassium adequately. We evaluated the safety and efficacy of potassium replacement therapy by retrospectively analyzing the incidence and severity of hypokalemia in 75 patients who received allo-HCT at our institution. 75% of patients developed hypokalemia during the allo-HSCT, and 44% of patients had grade 3-4 levels of hypokalemia. NRM was significantly higher in patients with grade 3-4 hypokalemia than in patients without severe hypokalemia (one-year NRM: 30% vs 7%, p=0.008). Although 75% of the patients required potassium replacement that exceeded the range of potassium chloride solutions package inserts in Japan, we did not experience any adverse events associated with hyperkalemia. Our current observations suggested that the Japanese package insert for potassium solution injection should be revised for potassium needs.

A Case of Vascular Malformation in the Buccal Fat Pad.

Vascular anomalies are categorized as vascular tumors or vascular malformations (VMs) based on the system of classification (updated in 2018) established by the International Society for the Study of Vascular Anomalies. In the orofacial region, such anomalies are most likely to occur in the lips or tongue, and only rarely in the buccal fat pad. This report describes a case of a VM in the buccal fat pad. A 47-year-old woman was referred to our hospital with a mass lesion in her left cheek. On palpation, an elastic, hard, painless, and mobile mass was found anterior to the left masseter muscle. Computed tomography, magnetic resonance imaging, and ultrasonography revealed a mass in the left buccal fat pad. The lesion was identified as a benign tumor and surgical excision performed under general anesthesia. Histopathological examination revealed that the lesion was composed of a large number of vascular structures of various sizes covered with endothelial cells. Based on the clinical and histopathological findings, a diagnosis of a venous VM was made. One year has passed since the operation and no recurrence has been observed. Long-term follow-up is planned.

Prognostic Value of Intraoperative Blood Transfusion in Patients with Adenocarcinoma of the Esophagogastric Junction.

Background and objectives: Adenocarcinoma of the esophagogastric junction (AEG) has a complicated surgical anatomy, due to which it sometimes induces excessive intraoperative blood loss that necessitates intraoperative blood transfusion (BTF). However, few reports have focused on the impact of BTF on the survival outcomes of patients with AEG. We aimed to evaluate the impact of BTF on AEG prognosis. Materials andMethods: We included 63 patients who underwent surgical resection for AEG at our hospital between January 2010 and September 2020. Clinicopathological characteristics and survival outcomes were compared between patients with (n = 12) and without (n = 51) BTF. Multivariate analysis was performed to identify the independent prognostic factors for overall survival. Results: None of the patients who underwent minimally invasive surgery received BTF. Patients who received BTF had a significantly worse 5-year survival rate than those who did not (67.8% vs. 28.3%, p = 0.001). BTF was an independent risk factor for overall survival (hazard ratio: 3.90, 95% confidence interval 1.30-11.7), even after patients who underwent minimally invasive surgery were excluded. Conclusions: BTF adversely affected the survival outcomes of patients with AEG who underwent curative surgery. To avoid BTF, surgeons should strive to minimize intraoperative bleeding.

Role of the small GTPase activating protein IQGAP1 in collagen phagocytosis.

Many adult connective tissues undergo continuous remodeling to maintain matrix homeostasis. Physiological remodeling involves the degradation of collagen fibers by the intracellular cathepsin-dependent phagocytic pathway. We considered that a multidomain, small GTPase activating protein, IQGAP1, which is involved in the generation of cell extensions, is required for collagen phagocytosis, possibly arising from its interactions with cdc42 and the actin-binding protein Flightless I (FliI). We examined the role of IQGAP1 in collagen phagocytosis by human gingival fibroblasts (HGFs) and by IQGAP1+/+ and IQGAP1-/- mouse embryonic fibroblasts. IQGAP1 was strongly expressed by HGFs, localized to vinculin-stained cell adhesions and sites where cell extensions are initiated, and colocalized with FliI. Immunoprecipitation showed that IQGAP1 associated with FliI. HGFs showed 10-fold increases of collagen binding, 6-fold higher internalization, and 3-fold higher ß1 integrin activation between 30 and 180 min after incubation with collagen. Compared with IQGAP1+/+ fibroblasts, deletion of IQGAP1 reduced collagen binding (1.4-fold), collagen internalization (3-fold), ß1 integrin activation (2-fold), and collagen degradation (1.8-fold). We conclude that IQGAP1 affects collagen remodeling through its regulation of phagocytic degradation pathways, which may involve the interaction of IQGAP1 with FliI.

[Post-transplant lymphoproliferative disorder localized to the colon presented with mild diarrhea after cord blood transplantation].

Post-transplant lymphoproliferative disorder (PTLD) usually develops with systemic symptoms, such as fever, generalized lymphadenopathy, and elevation in the lactate dehydrogenase level. Here, we present the case of a 65-year-old female patient with PTLD localized to the colon; the patient only had mild diarrhea without systemic symptoms. She had myelodysplastic syndrome and was treated with cord blood transplantation (CBT). She had a past medical history of sigmoid colon cancer treated with colonosectomy and adjuvant chemotherapy. After CBT, she achieved complete remission and was discharged after 60 days. Further, 79 days after CBT, she presented with abdominal pain. Computed tomography scan revealed adhesive ileus. The abdominal pain was resolved in 1 day with conservative treatment, however, mild diarrhea persisted. Therefore, we performed colonoscopy and found multiple ulcerative lesions in the upper colon. A pathological examination revealed PTLD. Furthermore, elevation of EBV-DNA in the blood was also confirmed. There was no detectable lesion on positron emission tomography-computed tomography (PET-CT) outside the colon; thus, we diagnosed PTLD localized into the colon that was successfully treated with rituximab. Our present experience suggests that it might be important to perform endoscopy and monitoring of EBV-DNA for early detection of PTLD, especially localized in the gastrointestinal tract.

[Angioimmunoblastic T-cell lymphoma complicated with various autoimmune abnormalities and myelofibrosis].

Angioimmunoblastic T-cell lymphoma (AITL) is frequently associated with immunological abnormalities, such as hypergammaglobulinemia, autoimmune cytopenia, and the presence of various autoantibodies. Few reports on AITL have also described the development of myelofibrosis resulting from the invasion of lymphoma cells that produced various cytokines, including TGF-ß. Interestingly, recent studies demonstrated that autoimmunity can directly cause autoimmune myelofibrosis (AIMF). Usually, bone marrow fibrosis associated with AIMF is rapidly improved by treatment. Here, we describe our experience with a case of AITL complicated with the presence of numerous autoimmune abnormalities, including positive Coombs, anti-nuclear antibody, anti-ds-DNA antibody, anti-phospholipid antibody, and cold agglutinin tests. The patient presented with severe bone marrow fibrosis (MF-3) at the initial diagnosis. After two courses of the CHASE therapy, myelofibrosis rapidly disappeared, and the autoimmune abnormalities were ameliorated. These findings suggest that the bone marrow fibrosis observed in this case was partly attributable to an AIMF-like mechanism.

Expression of Cytokeratin in Experimentally Created Inflammatory Cyst in Vivo and in Vitro.

The purpose of this study was to investigate the behavior of epithelial lining derived from Malassez's epithelial rest (MER) cells in experimentally created inflammatory cysts in vivo and in vitro. Porcine MER cells were cultured in vitro with or without interleukin (IL)-1ß (1 ng/ml) or IL-6 (1 ng/ml). Cell proliferation was assessed and expression levels of CK19 and CK13 mRNA determined using RT-PCR. In vivo, a cavity was created in the first molar of Sprague-Dawley male rats and tissue repair observed using immunohistochemical methods. In vitro, treatment with IL-1ß or IL-6 increased proliferation of MER cells and decreased expression of CK19 mRNA, but increased CK13 mRNA at day 1 (p<0.05). In vivo, at 2 weeks, CK19-positive epithelial cells were observed adjacent to the cementum, in the cystic lesion, and in connective tissue. At 3 weeks, they were only detected in cells adjacent to the connective tissue. Cells positive for CK13 were observed throughout the epithelium, except in cells adjacent to connective tissue at weeks 2 and 3. Exposure to IL-1ß and/or IL-6 induced proliferation and differentiation of MER cells.

Retinoic acid modulates lipid accumulation glucose concentration dependently through inverse regulation of SREBP-1 expression in 3T3L1 adipocytes.

It is well known that retinoic acid (RA) suppresses adipogenesis, although there are some contradicting reports. In this study, we examined the effect of extracellular glucose on RA-induced suppression of adipogenesis in 3T3L1 cell culture. When the cells were cultured in normal glucose medium (NG), the addition of RA suppressed lipid accumulation. However, when cultured in high glucose medium (HG), addition of RA to the cells enhanced lipid accumulation. These changes were accompanied by parallel alterations in fatty acid synthase (FAS) and sterol regulatory element-binding protein (SREBP)-1 gene expression. Transfection of SREBP-1 siRNA suppressed RA-induced enhancement of lipid accumulation and FAS expression in the cells cultured with HG. Transfection of the nuclear form of SREBP-1a cDNA into the cells cultured with NG inhibited RA-induced suppression of lipid accumulation and FAS expression. Moreover, RA- and HG-induced SREBP-1a expression occurred at the early phase of adipogenesis and was dependent on glucocorticoid to induce liver X receptor (LXR) ß, peroxisomal proliferator-activated receptor (PPAR) γ and retinoid X receptor (RXR), the key nuclear factors influencing the SREBP-1a gene expression. These results suggest that RA suppresses and enhances lipid accumulation through extracellular glucose concentration-dependent modulation of SREBP-1 expression.

[Atypical hemolytic uremic syndrome in an elderly patient successfully treated with eculizumab].

Herein, we present an elderly onset case of aHUS successfully treated with eculizumab. An 80-year-old woman with severe anemia, thrombocytopenia, and acute renal dysfunction was admitted to our hospital. A laboratory test revealed steep elevation in the LDH level, and the peripheral blood smear showed erythrocyte fragmentations. Accordingly, we diagnosed thrombotic microangiopathy, and treatment with plasma exchange was immediately initiated. In addition, she required hemodialysis because of rapid impairment of the renal function. After excluding Shiga toxin-producing Escherichia coli infection and malignancy and confirming her ADMTS13 activity above 10%, we diagnosed aHUS, according to the Japanese diagnostic criteria for aHUS. Next, we initiated treatment with eculizumab. Her hematological findings improved 23 days after the starting of eculizumab. In addition, her renal function gradually recovered, and hemodialysis was discontinued. The genetic test for several complement regulatory genes tested negative. The onset of aHUS is reported in children or young adults and is rarely reported in elderly. However, our case suggests the importance of precisely diagnosing aHUS and initiating early administration of eculizumab for improving the outcome even in elderly patients.

Congenital Epulis: A Case and Review of the Literature.

Congenital epulis is an unusual benign oral mucosal lesion in newborns with no tendency to recur after excision. The histogenesis of the lesion is unknown, but it is believed to be of mesenchymal origin. We describe a case of congenital epulis (20×10 mm) in the mandibular gingiva of a newborn. The mass, which was smooth-surfaced and pedunculated with a healthy color, was surgically removed at 5 months post-birth. Histologically, the tumor consisted mainly of large eosinophilic granular cells. Immunohistochemical studies revealed intense staining for vimentin, STRO-1, and CD44, suggesting that it was derived from mesenchymal cells. The literature and immunohistochemical profile of congenital epulis are also discussed.

Atypical MRI and Histopathological Findings in Dermoid Cyst.

On images, a dermoid cyst is often described as resembling a "sack of marbles" or "marbles in a bag". Typically, it comprises an inhomogeneity filled with multiple nodules in a fluid matrix on both computed tomography and magnetic resonance imaging (MRI). How it appears, however, will vary depending on its histological contents, which may cause confusion in arriving at a diagnosis. This report describes a dermoid cyst in the floor of the mouth of a 55 year-old woman that showed an atypical internal appearance on MRI. Most of the lesion showed homogeneous high signal intensity on T1 - and T2-weighted images, suggesting that it was derived from fat. A small area within the mass, however, showed moderate signal intensity almost equal to that of muscle on T1-weighted images and high signal intensity on fat-suppressed T2-weighted images. Given the location of the lesion, a dermoid cyst was one possible diagnosis. A lipoma or lipoma variants were also considered, however, based on signal intensity. Histopathological section of the excised specimen revealed a dermoid cyst with sebaceous glands in its walls and keratin in its cavity. Dermoid cysts show variation in their internal structures and contents. Since MRI can reflect such histological variation, signal intensity requires careful interpretation.

18F-FDG-PET/CT is effective in distinguishing myelofibrosis due to bone marrow infiltration of diffuse large B-cell lymphoma from triple-negative primary myelofibrosis.

Although myelofibrosis is mainly associated with myeloproliferative neoplasms (MPN), especially primary myelofibrosis (PMF), a variety of hematological malignancies, including acute myeloid leukemia, multiple myeloma and malignant lymphoma, also cause myelofibrosis with markedly varying degrees of severity. Thus, it is extremely important to accurately diagnose the underlying diseases that cause fibrosis in bone marrow. Analyses of JAK2, MPL and calreticulin gene mutations are useful for distinguishing MPN from other diseases, since 90% of MPN patients have a mutation in one of these genes. However, 10% of PMF patients do not have mutations in any of these genes, and these patients have a disease known as triple negative PMF. It is sometimes difficult to accurately distinguish triple negative PMF from secondary myelofibrosis caused by other diseases. Herein, we present a case of diffuse large B cell lymphoma (DLBCL) with bone marrow involvement, mimicking triple negative primary myelofibrosis. 18F-FDG-PET was useful for correctly diagnosing DLBCL.

Tyrosine Coupling Creates a Hyperbranched Multivalent Protein Polymer Using Horseradish Peroxidase via Bipolar Conjugation Points.

Protein polymers of covalently cross-linked protein monomers are highly attractive biomaterials because each monomer unit possesses distinct protein functions. Protein polymers often show enhancement effects on the function by integrating a large number of molecules into one macromolecule. The cross-linking site of component proteins should be precisely controlled to avoid diminishing the protein function. However, preparing protein polymers that are cross-linked site-specifically with a high cross-linking degree is a challenge. Here, we demonstrate the preparation of a site-specifically cross-linked protein polymer that has a hyperbranched polymer-like structure with a high cross-linking degree. A horseradish peroxidase (HRP) reaction was used to achieve the protein polymerization through a peptide tag containing a tyrosine residue (Y-tag). Y-tag sequences were introduced to both N- and C-termini of a model protein, protein G. The dual Y-tagged protein G (Y-pG-Y) was treated with HRP to form a Y-pG-Y polymer possessing average and maximum cross-linking degree of approximately 70-mer and 150-mer, respectively. The Y-pG-Y polymer shows the highest cross-linking degree among the protein polymers reported, which are completely soluble in water and cross-linked via covalent bonding. The Y-pG-Y was cross-linked site-specifically at the Tyr residue in the Y-tag, retaining its function, and the Y-pG-Y polymer showed extremely strong avidity against immunoglobulin G. The reactivities of N- and C-terminal Y-tags were evaluated, and we revealed that the difference in the radical formation rate by HRP was the key for yielding highly cross-linked protein polymers.

Latent association between low urine pH and low body weight in an apparently healthy population.

Low urine pH, a plausible predictor for chronic kidney disease and metabolic disorders, is often observed in obese individuals. However, the association between low urine pH and low body weight is equivocal. We examined clinical parameters including urine pH and body mass index (BMI) in a cross-sectional study of 3629 apparently healthy Japanese adults aged 25-80 years who underwent a health-screening check-up. Urine pH was lower and the prevalence of proteinuria was significantly higher in subjects with BMI of ≥ 27.0 kg/m(2) compared with those with BMI of 21.0-22.9 kg/m(2). By contrast, hematuria was more prevalent in subjects with BMI of ≤ 20.9 kg/m(2). Logistic regression analysis showed that BMI of ≥ 27.0 kg/m(2) was significantly associated with low urine pH (≤ 5.5), which remained significant after adjustment for relevant confounders including age, sex, proteinuria, estimated glomerular filtration rate, urine density, hematuria, smoking status, and daily alcohol drinking. However, the association disappeared after further adjustment for serum uric acid. In contrast, the association between low urine pH and BMI of ≤ 19.0 kg/m(2) was significant after adjustment for age and sex and rather strengthened by the further adjustment for serum uric acid. In conclusion, low urine pH may be independently associated with low BMI. However, the underlying mechanisms of low urine pH in low body weight may differ from those in high body weight.

The association of serum sodium and chloride levels with blood pressure and estimated glomerular filtration rate.

BACKGROUND: High serum sodium (sNa) concentrations may be associated with hypertension, which deteriorates kidney function. However, it is equivocal whether high sNa concentrations are associated with impaired kidney function independently of blood pressure (BP) or serum chloride (sCl). Therefore, we addressed this issue in an apparently healthy population. METHODS: Clinical variables including estimated glomerular filtration rate (eGFR) were examined in 3603 men and women (aged 25-75 years) who underwent health-screening check-ups. sNa concentrations were classified into five categories. RESULTS: Most parameters, including age and BP, increased with increasing sNa, whereas eGFR decreased. Logistic regression analysis showed that, compared with low-normal sNa (≤ 140 mEq/l), high sNa (≥ 144 mEq/l) was significantly associated with elevated BP (≥ 130/85 mmHg) even after adjustment for blood hematocrit, eGFR, serum potassium (sK) concentration and sCl. The highest sNa category was significantly associated with reduced eGFR (< 60 ml/min/1.73 m(2)) independently of elevated BP. Unlike adjustment for sK, adjustment for sCl strengthened the association between high sNa and elevated BP but attenuated the association between high sNa and reduced eGFR. CONCLUSIONS: These results suggest that high sNa concentrations, even within the normal range, are independently associated with elevated BP and impaired kidney function. These associations may be substantially modified by sCl.

Prevalent hyperglycemia in older obese population and age-dependent convergence of obese indices: Results of a cross-sectional study of Japanese generations over the adult life span.

PURPOSE/AIM: An age-dependent decline has been observed in the association between obesity and type 2 diabetes, a major comorbidity of obesity, although the evidence is limited. Therefore, we investigated the association and the plausible underlying mechanism in a large epidemiological study. MATERIALS AND METHODS: We examined the association between the degree of obesity and hyperglycemia in five age groups (20-39, 40-49, 50-59, 60-69, and 70-85 years) in a cross-sectional study of 78,776 apparently healthy Japanese men and women who underwent a checkup in 2012. Hyperglycemia was defined as glycosylated hemoglobin (HbA1c) of ≥5.7% and/or pharmacotherapy for diabetes. RESULTS: The incidence of hyperglycemia was three times higher in the 70-85-year-old group (62%) than in the 20-39-year-old group (20%) in obese individuals (body mass index [BMI] ≥ 27.0 kg/m(2)). However, the incidence was 12 times higher in reference-weight individuals (21.0-22.9 kg/m(2); 48% and 4%, respectively). As age increased, mean BMI and waist circumference approached certain non-obese ranges (22-24 kg/m(2) and 80-86 cm, respectively), even in hyperglycemic subjects. Logistic regression analysis revealed an age-dependent decline in the association between obesity and hyperglycemia, relative to that in reference-weight individuals. CONCLUSIONS: Our results confirmed the previously reported age-dependent decline in the association between obesity and hyperglycemia, although hyperglycemia was still prevalent in older obese subjects than in older reference-weight subjects. Therefore, the decline in the association may be accelerated due to an age-dependent increase in the prevalence of hyperglycemia in reference-weight individuals.