Search

Nobuhiro Fujioka,1 Masahiro Kitabatake,2 Noriko Ouji-Sageshima,2 Takahiro Ibaraki,1 Makiko Kumamoto,1 Yukio Fujita,1 Shigeto Hontsu,1 Motoo Yamauchi,1 Masanori Yoshikawa,1 Shigeo Muro,1 Toshihiro Ito2 1Department of Respiratory Medicine, Nara Medical University, Kashihara, Nara, Japan; 2Department of Immunology, Nara Medical University, Kashihara, Nara, JapanCorrespondence: Toshihiro ItoDepartment of Immunology, Nara Medical University, 840 Shijo-cho, Kashihara, Nara, 634-8521, JapanTel +81-744-22-3051Fax +81-744-29-7503Email toshi-ito@naramed-u.ac.jpPurpose: Chronic obstructive pulmonary disease (COPD) is a worldwide problem because of its high prevalence and mortality. However, there is no fundamental treatment to ameliorate their pathological change in COPD lung. Recently, adipose-derived mesenchymal stem cells (ADSCs) have attracted attention in the field of regenerative medicine to repair damaged organs. Moreover, their utility in treating respiratory diseases has been reported in some animal models. However, the detailed mechanism by which ADSCs improve chronic respiratory diseases, including COPD, remains to be elucidated. We examined whether human ADSCs (hADSCs) ameliorated elastase-induced emphysema and whether hADSCs differentiated into alveolar epithelial cells in a murine model of COPD.Methods: Female SCID-beige mice (6 weeks old) were divided into the following four groups according to whether they received an intratracheal injection of phosphate-buffered saline or porcine pancreatic elastase, and whether they received an intravenous injection of saline or hADSCs 3 days after intratracheal injection; Control group, hADSC group, Elastase group, and Elastase-hADSC group. We evaluated the lung function, assessed histological changes, and compared gene expression between hADSCs isolated from the lung of Elastase-hADSC group and naïve hADSCs 28 days after saline or elastase administration.Results: hADSCs improved the pathogenesis of COPD, including the mean linear intercept and forced expiratory volume, in an elastase-induced emphysema model in mice. Furthermore, hADSCs were observed in the lungs of elastase-treated mice at 25 days after administration. These cells expressed genes related to mesenchymal–epithelial transition and surface markers of alveolar epithelial cells, such as TTF-1, β-catenin, and E-cadherin.Conclusion: hADSCs have the potential to improve the pathogenesis of COPD by differentiating into alveolar epithelial cells by mesenchymal–epithelial transition.Keywords: chronic obstructive pulmonary disease, mesenchymal–epithelial transition, adipose derived mesenchymal stem cell, pulmonary function test

Antiresorptive-related osteonecrosis of the jaw (ARONJ) is a rare but serious adverse event associated with bone-modifying agents (BMAs) and affects patients in the terminal stages of cancer. Molecular targeting drugs (MTDs), anti-vascular endothelial growth factor receptor (VEGFR), and anti-epidermal growth factor receptor (EGFR) drugs are essential in various cancer treatments, although MTDs are risk factors for ARONJ. However, the mechanism through which MTDs affect treatment prognosis of ARONJ remains unclear. Therefore, we investigated the potential inhibitory factors for healing in the conservative therapy of ARONJ with a focus on MTDs. Sixty patients who were administered BMAs for the treatment of malignancies and who underwent conservative treatment for ARONJ were assessed. The healing rate of ARONJ for each risk factor was retrospectively evaluated. Among the 60 patients, 27 were male and 33 were female. The median age was 67 years, and the median follow-up period was 292 (range 91–1758) days. The healing rate was lower in those treated with both zoledronic acid (Za) and denosumab (Dmab) than in those treated with Za or Dmab alone (0% vs. 28.8%, p = 0.03). Regarding the administration of MTDs, the treatment rate with anti-VEGFR drugs was 7.1% (p = 0.04), anti-EGFR drugs was 12.5% (p = 0.18), and without MTDs was 36.8%. In the conservative treatment of ARONJ, the administration of several BMAs and anti-VEGFR drugs was the factor contributing to the inhibition of healing.

The objectives of this study were to evaluate survival in 141 patients with stage II-IV oral squamous cell carcinoma (OSCC) treated with preoperative intra-arterial chemotherapy with docetaxel, cisplatin, and peplomycin combined with intravenous chemotherapy using 5-fluorouracil (IADCPIVF) via the superficial temporal artery, and to clarify the prognostic factors. The study population included 59 patients with stage II OSCC, 34 with stage III, and 48 with stage IV. After IADCPIVF, 139 patients underwent surgery; minimally invasive surgeries (MIS) including excisional biopsy were performed on 96 patients with a remarkably good response to IADCPIVF. The primary tumour response rate was 99.3% (complete response rate 56.7%, good partial response rate 17.0%, fair partial response rate 25.5%). Additionally, there were no serious adverse events associated with IADCPIVF. The 5-year overall survival rate was 74.6% (stage II 83.6%, stage III 72.7%, stage IV 64.8%). In the multivariate analysis of survival, T classification and clinical tumour response were significant prognostic factors. Eight (8.3%) of the patients who received MIS had primary recurrence and six were salvaged. In conclusion, IADCPIVF is safe and efficacious for treating OSCC, and MIS could reduce the extent of primary tumour resection in the case of a remarkably good response.

BackgroundVariants in the type IV collagen gene (COL4A1/2) cause early-onset cerebrovascular diseases. Most individuals are diagnosed postnatally, and the prenatal features of individuals with COL4A1/2 variants remain unclear.MethodsWe examined COL4A1/2 in 218 individuals with suspected COL4A1/2-related brain defects. Among those arising from COL4A1/2 variants, we focused on individuals showing prenatal abnormal ultrasound findings and validated their prenatal and postnatal clinical features in detail.ResultsPathogenic COL4A1/2 variants were detected in 56 individuals (n=56/218, 25.7%) showing porencephaly (n=29), schizencephaly (n=12) and others (n=15). Thirty-four variants occurred de novo (n=34/56, 60.7%). Foetal information was available in 47 of 56 individuals, 32 of whom (n=32/47, 68.1%) had one or more foetal abnormalities. The median gestational age at the detection of initial prenatal abnormal features was 31 weeks of gestation. Only 14 individuals had specific prenatal findings that were strongly suggestive of features associated with COL4A1/2 variants. Foetal ventriculomegaly was the most common initial feature (n=20/32, 62.5%). Posterior fossa abnormalities, including Dandy-Walker malformation, were observed prenatally in four individuals. Regarding extrabrain features, foetal growth restriction was present in 16 individuals, including eight individuals with comorbid ventriculomegaly.ConclusionsPrenatal observation of ventriculomegaly with comorbid foetal growth restriction should prompt a thorough ultrasound examination and COL4A1/2 gene testing should be considered when pathogenic variants are strongly suspected.

Aim. To evaluate the feasibility of a newly developed prototype MRI projection mapping (PM) system for localization of invasive breast cancer before breast-conserving surgery. Methods. This prospective study enrolled 10 women with invasive breast cancer. MRI was performed in both prone and supine positions. The tumor location was drawn on the breast skin using palpation and sonography while referring to the prone MRI (i.e., a conventional method). A maximum intensity projection image generated from the supine MRI was projected using our PM system, and the tumor location was drawn. The PM system consisted of a projector and a camera and was used to measure the shape of the breast surface using the structured light method. Breast-conserving surgery was performed based on the conventional method. We compared the tumor size and location between the PM and conventional methods or pathology. Results. There were no significant differences in the maximum diameters of invasive cancers between the PM system and the conventional method or pathology. The maximum discrepancy in tumor location between the PM and conventional method was 3–8 mm. Conclusions. This PM system may support breast-conserving surgery by showing the tumor size and location on the breast surface.

This retrospective study investigated the effect of perioperative oral care intervention on postoperative outcomes in patients undergoing lung cancer resection, in terms of the length of postoperative hospital stay and the incidence of postoperative respiratory infections. In total, 585 patients underwent lung resection for lung cancer, 397 received perioperative oral care intervention, whereas the remaining 188 did not. This study retrospectively investigated the demographic and clinical characteristics (including postoperative complications and postoperative hospital stay) of each group. To determine whether perioperative oral care intervention was independently associated with either postoperative hospital stay or postoperative respiratory infections, multivariate analysis, multiple regression analysis, and multivariate logistic regression analysis were conducted. Parameters significantly associated with a prolonged postoperative hospital stay in lung cancer surgery patients were older age, postoperative complications, increased intraoperative bleeding, more invasive operative approach (e.g., open surgery), and lack of perioperative oral care intervention (standard partial regression coefficient (s) = 0.083, p = 0.027). Furthermore, older age and longer operative time were significant independent risk factors for the occurrence of postoperative respiratory infections. Lack of perioperative oral care intervention was a potential risk factor for the occurrence of postoperative respiratory infections, although not statistically significant (odds ratio = 2.448, 95% confidence interval = 0.966–6.204, p = 0.059). These results highlight the importance of perioperative oral care intervention prior to lung cancer surgery, in order to shorten postoperative hospital stay and reduce the risk of postoperative respiratory infections.

Objective: Knee pain is commonly observed among older adults. Therefore, the prevention of knee pain in older adults is a major public health issue. This study aimed to clarify factors relevant to knee pain among older adults. Methods: This study targeted all independent older adults (N = 6661) living in a local municipality in Japan. Participants’ health status and lifestyle habits were surveyed using a questionnaire. The survey was conducted from 15 January to 14 February 2016. Relationships between knee pain and physical activity, sitting time, nutrition, drinking, smoking, or body mass index (BMI) were examined using logistic regression analysis. Odds ratios (OR) and 95% confidence intervals (CI) adjusted for several confounding factors were calculated. Results: Older adults of 5311 responded to the questionnaire and 1843 reported knee pain. The prevalence of knee pain was 34.8%. Knee pain was significantly associated with BMI (OR: 0.60, 95% CI: 0.51 - 0.69, P P P P = 0.001). Conclusions: This study suggests that one in three independently-living older adults experiences chronic knee pain and that physical activity, BMI, and nutritional status are associated with knee pain.

Myeloid sarcoma (MS) is defined as a tumorous mass of myeloblasts or immature myeloid cells involving an extramedullary anatomic site. MS occurs in 3 to 8% of patients with acute myeloid leukemia. The overwhelming majority of MS occurs in the skin, bones, and gastrointestinal tract; intraoral MS (IMS) is extremely rare. We describe a case of MS of the mandibular gingiva in a patient with acute myeloid leukemia that was in remission. We also present a review of the English and Japanese literature with a special focus on the management and prognosis of intraoral MS. The patient was discharged while in remission 8 months after the initial examination. The prognosis of IMS is extremely poor in general, and a diagnostic delay can prevent adequate therapy by hematologists and oncologists. All dental clinicians must keep the possibility of IMS in mind and carefully examine all patients with AML.

The rare blood phenotype D-- is characterized by the absence of RhCcEe antigens. Women with this blood type who have experienced previous pregnancies may produce anti-Rh17 antibodies, which may cause severe fetal hemolytic anemia or fetal death in subsequent pregnancies. We report successful management of a pregnancy associated with fetal hemolytic disease owing to high titers of anti-Rh17 (1:4096) in a woman with a history of a pregnancy with fetal hydrops and intrauterine fetal death. During her second pregnancy, she received two sets of plasma exchange (PE) per week from weeks 12 till 20. Intrauterine transfusions (IUTs) were performed at 26, 27, 29, and 31 weeks. A male infant was born at 32 weeks and 4 days by normal vaginal delivery, with a birth weight of 1916 g (+ 0.16 SD). He received an exchange transfusion on day 0, immunoglobulin (intravenous immunoglobulin: 1 g/kg) on days 0 and 1, and photo therapy from days 0 to 6. He showed normal development without neurological abnormality and was discharged from the hospital on day 36. We successfully prevented complications caused by the presence of anti-Rh17 antibodies in the mother during pregnancy. The IUT and maternal PE may have promoted this favorable outcome.

Background: Heart rate (HR) reduction by β-blocker might not benefit patients with heart failure and reduced ejection fraction (HFrEF) with atrial fibrillation (AF). Methods and Results: The J-CHF study was a prospective randomized multicenter trial that assigned 360 HFrEF patients to a 2.5 mg/5 mg/20 mg target dose of carvedilol. Carvedilol was uptitrated over 8 weeks and then the dose was fixed. Of 321 patients available for analysis, AF was identified in 65 (20%). Using the median absolute change in HR at 32 weeks (∆HR), the subjects were further divided into group A (∆HR >-6 beats/min) and B (∆HR ≤-6 beats/min). Both in sinus rhythm (SR) and AF, baseline characteristics and achieved carvedilol dose were similar between groups A and B. In SR, the time-dependent change in left ventricular EF (LVEF) and LV end-diastolic dimension (LVEDD) over 56 weeks was more favorable in B compared with A (∆LVEF, P=0.036; ∆LVEDD, P=0.047), and ∆HR was independently associated with ∆LVEF (P=0.040). Group B had a lower rate of the primary endpoint, defined as a composite of death and hospitalization due to cardiovascular causes including acute decompensated HF at 3 years (P=0.002). ∆HR was an independent predictor of the primary endpoint (P=0.01), but this was not observed in AF. Conclusions: Response to the carvedilol HR reduction might differ in HFrEF between SR and AF.

Background/aim: The current study aimed to identify biomarkers for differentiating between patients with oral cancer (OC) and healthy controls (HCs) on the basis of the comprehensive proteomic analyses of saliva samples by using liquid chromatography-mass spectrometry (LC-MS/MS). Patients and Methods: Unstimulated saliva samples were collected from 39 patients with OC and from 31 HCs. Proteins in the saliva were comprehensively analyzed using LC-MS/MS. To differentiate between patients with OC and HCs, a multiple logistic regression model was developed for evaluating the discriminatory ability of a combination of multiple markers. Results: A total of 23 proteins were significantly differentially expressed between the patients with OC and the HCs. Six out of the 23 proteins, namely α-2-macroglobulin-like protein 1, cornulin, hemoglobin subunit β, Ig ĸ chain V-II region Vĸ167, kininogen-1 and transmembrane protease serine 11D, were selected using the forward-selection method and applied to the multiple logistic regression model. The area under the curve for discriminating between patients with OC and HCs was 0.957 when the combination of the six metabolites was used (95% confidence interval=0.915-0.998; p

Background: When anatomic structures are excised so widely that the resulting defect cannot be closed directly during an operation, reconstruction of the defect is necessary. Prosthetic mesh is often used to reconstruct large defects because it is readily available and technically easy to use. However, the use of prosthetic material is contraindicated in cases of concomitant contamination due to the risk of mesh infection. We describe our experience of surgical repair using an autologous free fascia lata graft in 5 patients at risk of such infection. Methods: The procedure was performed for incisional hernia repair in 4 patients and reconstruction of the diaphragm after cytoreduction of recurrent ovarian cancer in 1. All patients underwent other concomitant procedures associated with contamination, such as colorectal resection, and these patients were included in a retrospective chart review. Results: Wound-related morbidity was observed in 1 patient whose drain culture was positive. This infection was resolved conservatively. No postoperative wound events required removal of the fascia graft, and there was no hernia occurrence during follow-up. Conclusion: Based on our clinical experience, we conclude that surgical repair using a free fascia lata graft is safe and effective, especially in patients with a risk of bacterial contamination.

A 40-year-old male without any past medical history accidentally swallowed a titanium dental instrument (reamer) for root canal treatment. A cathartic was prescribed at a local hospital, and the course was observed. However, since the reamer was not excreted in feces, he was referred to our hospital. After admission, CT, lower gastrointestinal endoscopy, and barium enema revealed the migration of a foreign body into the appendix and its protrusion into the intraperitoneal cavity. As an emergency operation, laparoscopic appendectomy including the foreign body was performed. The following course was favorable without postoperative complications, and he was discharged on the 2nd hospital day. We report a patient with appendiceal perforation due to a foreign body (dental instrument for root canal treatment) in the appendix.

Congenital epidermolysis bullosa is a rare, genetic condition in which even slight stimulation can cause blistering of the skin or mucosa. While previous reports of treatments requiring general anesthesia in these patients were focused on anesthesia-related procedures, such as endotracheal intubation, no report has described specific management required for these patients during surgery, such as preparation of the surgical site, fixation of infusion lines and other tubes, and adjustment of the operation table. This is probably the first report to address these issues. This report presents a case of recessive dystrophic congenital epidermolysis bullosa in which open hepatectomy was safely performed.

BACKGROUND Anemia portends a poor clinical outcome in patients with chronic heart failure (CHF). However, its mechanism remains unknown. We sought to elucidate the effect of anemia on patients with HF with reduced ejection fraction (HFrEF) who receive carvedilol therapy.Methods and Results:J-CHF study was a prospective, randomized, multicenter trial that assigned 360 HFrEF patients to 2.5 mg/5 mg/20 mg carvedilol groups according to the target dose. At baseline 70 patients (19%) had anemia ([A]) defined as hemoglobin level (Hb)

Background and Aim Eradication of hepatitis C virus (HCV) with interferon (IFN)-based therapy has been reported to reduce all-cause mortality in patients with chronic HCV infection. However, the impact of HCV eradication on non–liver-related mortality and causes of death has not been sufficiently investigated in patients with progressive HCV-related fibrosis. Methods We enrolled 784 chronic HCV patients with progressive liver fibrosis (aspartate aminotransferase to platelet ratio index >1). Cause of death, incidence of hepatocellular carcinoma, and all-cause mortality including non–liver-related mortality were analyzed. Results Of these 784 patients, 170 achieved sustained virological response (SVR) (eradication of HCV) with IFN-based therapy (IFN-SVR), and 614 did not receive IFN-based therapy (non-IFN patients, chronic HCV infection). The median follow-up duration was 10.3 years. Two hundred seventy-three patients died during follow-up (liver-related death, n = 171; non–liver-related death, n = 102). The mortality rate from non–liver-related disease was 63.6% (7/11) in IFN-SVR patients and 36.3% (95/262) in non-IFN patients, respectively. In multivariate analysis, the eradication of HCV associated with not only hepatocellular carcinoma incidence (hazard ratio (HR), 0.162; 95% confidence interval (CI), 0.092–0.284), and all-cause mortality (HR, 0.094; 95% CI, 0.047–0.187), but non–liver-related mortality (HR, 0.286; 95% CI, 0.127–0.644) as well. Conclusions Eradication of HCV reduced both liver-related and non–liver-related mortality in patients with progressive HCV-related fibrosis.

The information presented herein extends our recent study of TTT (Trial for Triplet Antiemetic Therapy). One of our main clinical questions has been whether a 2nd generation serotonin receptor antagonist (5-HT3ra) would be superior to 1st generation 5-HT3ra when administering triplet antiemetic therapy for the prevention of chemotherapy induced nausea & vomiting (CINV), since a prior Japanese trial demonstrated palonosetron to be superior to granisetron for controlling the delayed phase of CINV induced by highly emetogenic chemotherapy (HEC) and to doublet antiemetic therapy including dexamethasone for anthracycline and cyclophosphamide containing regimens (AC). In this study, we assessed the efficacies of 1st and 2nd generation 5-HT3ra agents for use as triplet antiemetic therapy for AC, by monitoring CINV, focusing especially daily CR in the delayed phase. Between 2012 and 2015, 491 women with breast cancer receiving AC were recruited from 11 institutions in Japan, and randomly assigned to either single-dose palonosetron (0.75mg) or granisetron (40μg/kg) prior to chemotherapy on day 1, both with dexamethasone (9.9 mg intravenously) and aprepitant (125mg orally) on day 1 followed by additional doses (80mg orally) on days 2 and 3. Age, institution and habitual alcohol intake were used as stratification factors. The primary endpoint was a complete response (CR). Statistical analysis was done by Mantel-Haenszel Method. This trial was registered with UMIN000007882. All 491 patients were included in efficacy analyses (ITT): 246 patients in the palonosetron group and 245 in the granisetron group. We previously reported that the difference in CR during the delayed phase, i.e. 24 hours after the administration of AC, did not reach statistical significance (53.8% vs 58.5%) in MASCC 2016. However, daily CR in the palonosetron group was much higher than that in the granisetron group after 48 hours. Palonosetron showed better efficacy in controlling CINV during the late period of the delayed phase, i.e. 48 hours after AC administration, than granisetron as triplet antiemetic therapy for AC. The pattern of CINV reportedly shows two peaks including an acute phase caused by serotonin and a delayed phase caused by substance P, though the pattern of CINV with triplet antiemetic therapy administration might be different if the suppression of each of these peaks were to be achieved more efficiently. CINV may not be divided into two phases in the future, or the borderline area between the acute and delayed phases may require revision. The analysis of the late period of the delayed phase was ad hoc in this trial. However, when conducting studies related to CINV, it might be worthwhile to revise the borderline area between the two phases of CINV to facilitate elucidating the mechanisms underlying this potentially debilitating side effect of chemotherapy. Citation Format: Ogata H, Saito M, Tsuneizumi M, Kutomi G, Hosoya K, Kawai Y, Sugizaki K, Katsumata N, Senuma K, Kitabatake T, Suda M, Uomori T, Miura K, Kurata M, Nitta Y, Yonemoto N, Matsuoka J. Difference between 1st and 2nd generation serotonin receptor antagonists in triplet antiemetic therapy for highly emetogenic chemotherapy in breast cancer patients – according to recent multi-institutional double-blind randomized clinical research on the AC regimen [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P5-11-03.

The purpose of this research is to develop a useful training device for people with gait disorders. The proposed device was evaluated by some experiments such as the timed up and go test (TUG) and measuring of step length in Parkinson's disease. The training effect with this device appeared to improve gait freezing and step length. The proposed device can be expected to be easy to use for training at home.

OBJECTIVE This study was conducted to distinguish salivary metabolites in oral squamous cell carcinoma (OSCC) from those in oral lichen planus (OLP) to identify practical biomarkers for the discrimination of OSCC from OLP. SUBJECTS AND METHODS Whole unstimulated saliva samples were collected from patients with OSCC (n = 34) and OLP (n = 26). Hydrophilic metabolites in the saliva samples were comprehensively analysed by capillary electrophoresis mass spectrometry. To evaluate the discrimination ability of a combination of multiple markers, a multiple logistic regression (MLR) model was developed to differentiate OSCC from OLP. RESULTS Fourteen metabolites were found to be significantly different between the OSCC and OLP groups. Among them, indole-3-acetate and ethanolamine phosphate were used to develop the MLR model. The combination of these two metabolites showed a high area under the receiver operating characteristic curve (0.856, 95% confidential interval: 0.762-0.950; p

Background Circulating endotoxins including lipopolysaccharides (LPS) cause brain responses such as fever and decrease of food and water intake, while pre-injection of endotoxins attenuates these responses. This phenomenon is called endotoxin tolerance, but the mechanisms underlying it remain unclear. The subfornical organ (SFO) rapidly produces proinflammatory cytokines including interleukin-1β (IL-1β) in response to peripherally injected LPS, and repeated LPS injection attenuates IL-1β production in the SFO, indicating that the SFO is involved in endotoxin tolerance. The purpose of this study is to investigate features of the IL-1β source cells in the SFO of LPS-non-tolerant and LPS-tolerant mice. Methods We first established the endotoxin-tolerant mouse model by injecting LPS into adult male mice (C57BL/6J). Immunohistochemistry was performed to characterize IL-1β-expressing cells, which were perivascular macrophages in the SFO. We depleted perivascular macrophages using clodronate liposomes to confirm the contribution of IL-1β production. To assess the effect of LPS pre-injection on perivascular macrophages, we transferred bone marrow-derived cells obtained from male mice (C57BL/6-Tg (CAG-EGFP)) to male recipient mice (C57BL/6N). Finally, we examined the effect of a second LPS injection on IL-1β expression in the SFO perivascular macrophages. Results We report that perivascular macrophages but not parenchymal microglia rapidly produced the proinflammatory cytokine IL-1β in response to LPS. We found that peripherally injected LPS localized in the SFO perivascular space. Depletion of macrophages by injection of clodronate liposomes attenuated LPS-induced IL-1β expression in the SFO. When tolerance developed to LPS-induced sickness behavior in mice, the SFO perivascular macrophages ceased producing IL-1β, although bone marrow-derived perivascular macrophages increased in number in the SFO and peripherally injected LPS reached the SFO perivascular space. Conclusions The current data indicate that perivascular macrophages enable the SFO to produce IL-1β in response to circulating LPS and that its hyporesponsiveness may be the cause of endotoxin tolerance. Electronic supplementary material The online version of this article (10.1186/s12974-019-1431-6) contains supplementary material, which is available to authorized users.

Background Intracranial pseudoaneurysm formation due to a ruptured non-traumatic aneurysm is extremely rare. We describe the radiological findings and management of pseudoaneurysms due to ruptured cerebral aneurysms in our case series and previously reported cases. Patients and methods Four additional and 20 reported patients presenting with subarachnoid hemorrhage (SAH) are included. Radiological findings and clinical features of these patients were reviewed. Results In our series, three-dimensional computed tomographic angiography (3D-CTA) and/or angiography showed an irregular- or snowman-shaped cavity extending from the parent artery. The radiological examination additionally revealed delayed filling and retention of contrast medium. These findings were the same as previously reported cases. One patient underwent direct clipping of the true aneurysm. For the other three patients with aneurysms at the basilar and anterior communicating arteries, the true portion of the aneurysm was embolized with platinum coils. During the procedures, care was taken not to insert the coils into the distal pseudoaneurysm portion to prevent rupture. The review of 24 cases revealed that the location of the aneurysms was most frequent in the anterior communicating artery (41.7%), and 86.7% of patients were in a severe stage of SAH (>Grade 3 in WFNS or Hunt & Kosnik grading) implying abundant SAH. Conclusions Pseudoaneurysm formation in SAH after non-traumatic aneurysm rupture is rare. However, in cases with an irregular-shaped aneurysm cavity, pseudoaneurysm formation should be taken into consideration.

Cycling is a way for older adults to be physically active and remain healthy. This descriptive epidemiological study investigated the role of sociodemographic, biological, behavioral, and psychological correlates associated with cycling among community-dwelling older adults in Japan. This cross-sectional study, conducted in 2010, included 1,938 community-dwelling older adults aged 65 to 74 years, from three cities in Japan: Bunkyo City (urban area) and Fuchu City (suburban area) in Tokyo, and Oyama City in Shizuoka (rural area). Participants were randomly selected from resident registries and a questionnaire was mailed to each one (response rate of 75.7%). All data was self-reported, including cycling time. Multivariable logistic regression analysis was used to calculate the adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for cycling. The proportion of men and women who cycled was 30.1% and 28.3%, respectively. Cycling was strongly associated with residential area: in men, Fuchu (suburban) (ORs = 3.15, 95% CIs = 2.20-4.52), Oyama (rural) (0.14, 0.08-0.25); in women, Fuchu (suburban) (4.15, 2.80-6.16), Oyama (rural) (0.21, 0.11-0.40), compared to Bunkyo (urban). Moreover, cycling was inversely associated with being underweight (0.26, 0.08-0.80) in men; for women, it was inversely associated with living alone (0.51, 0.29-0.90) and with not working (0.56, 0.38-0.84), and positively associated with not driving often (2.81, 1.47-5.40), and with not possessing a driver’s license (2.16, 1.23-3.79). The prevalence of cycling among older adults is relatively high in Japan. However, it varies greatly depending on residential area. Differences in residential areas may be taken into account to promote effective strategies for cycling.

Aim The rate of hepatocellular carcinoma (HCC) development is reportedly lower in patients with chronic hepatitis C virus (HCV) who have achieved a sustained virological response (SVR) than in patients who were unresponsive to therapy. However, the development of HCC is sometimes observed in patients with SVR. Therefore, we clarified the predictive power of clinical factors for HCC incidence in patients with SVR using receiver operating characteristic (ROC) curve analysis that takes time dependence into account. Methods A total of 571 patients with HCV who achieved SVR with interferon-based therapy were enrolled. Univariate and multivariate Cox proportional hazards models and time-dependent ROC curves were used to analyze clinical factors associated with the development of HCC. Results Twenty-four patients developed HCC during the follow-up period (median duration, 9.0 years). The 5-, 10-, 15-, and 20-year cumulative incidence rates for HCC were 1.7%, 4.8%, 5.8%, and 6.6%, respectively. Multivariate Cox proportional hazards models showed that older age (hazard ratio [HR], 3.648), male sex (HR, 7.560), lower platelet count at 24 weeks after the end of treatment (SVR24) (HR, 3.939), and higher α-fetoprotein (AFP) at SVR24 (HR, 3.630) were independently associated with HCC development. In addition, time-dependent ROC analysis showed that, compared to platelet count at SVR24, AFP at SVR24 had higher predictive power for HCC incidence approximately 7 years after SVR. Conclusions Elevated AFP at SVR24 is a risk factor for HCC in patients with HCV, even those who achieve SVR. α-Fetoprotein is a good predictor of HCC development.

A 71-year-old Japanese man was diagnosed as having stage I primary follicular lymphoma (FL) of the duodenum according to Lugano International Conference Classification and began receiving annual checkups. Endoscopic examination disclosed white villi swelling with depressed red mucosal lesions. Biopsy specimens from the area of white villi exhibited histopathological features that met the diagnostic criteria for low-grade FL. The depressed red lesions gradually enlarged over six years of follow-up. A biopsy of the white villi swelling revealed distinct well-circumscribed follicles with attenuated mantles in the lamina propria that were positive for CD20, bcl-2, and CD10. Histological findings from the depressed red lesions at 5.5 years after the initial diagnosis were compatible for FL. However, biopsy specimens 6 months later obtained from the same lesions showed a mixture of larger mononuclear cells. These follicular cells were positive for CD20 and bcl-2, but not for CD10, indicating the presence of diffuse large B-cell lymphoma (DLBCL). This case shows altered endoscopic findings in the course of DLBCL development from FL. When depressed red lesions are detected in the background of white villi swelling, repeated biopsies should be performed from both lesions.

Most women experience unpleasant symptoms during their menopausal transition. The most common menopausal symptoms are hot flashes, sleep disturbances, muscle or joint pains, and irritability.1 In addition, approximately 25% of perimenopausal women suffer from depressive symptoms.2 Hormone therapy (HT) is an effective treatment for such symptoms; however, many women seek other treatment with fewer adverse effects and health risks than those associated with HT.3 Evidence needs to be accumulated regarding possible lifestyle modification interventions that alleviate menopausal and depressive symptoms. Exercise may help alleviate menopausal and depressive symptoms among middle-aged women, but insufficient evidence currently exists to support this theory.4 Aerobic exercise training for 6 months has been reported to improve menopausal symptoms5 and quality of life.6 Furthermore, a prospective study showed a relationship between moderate- to vigorous-intensity exercise and depressive symptoms in middle-aged women.7 In a review of randomized controlled trials (RCTs) involving adults with depression, the effect size of exercise on depression was −0.62 compared with that in the control group, indicating a moderate clinical effect.8 Although the data on the effects of exercise in perimenopausal women have been equivocal, recent reviews clearly point to the need for more evidence based on RCTs.4,9 In addition, most of the previous studies focused on the effects of moderate- to vigorous-intensity exercise, which may actually trigger hot flashes in these women.10 Light-intensity exercise is not likely to increase the occurrence of hot flashes, but has a positive impact on psychological well-being.11,12 Little is, however, known about the effects of light-intensity exercise on menopausal and depressive symptoms in middle-aged women.13,14 Light-intensity exercise is defined as less than three metabolic equivalents (METs).15 One common, light-intensity exercise is stretching, which is regarded as providing approximately 2.3 METs.16 Previous reports have indicated that daily stretching for 15 minutes suppresses sympathetic nervous activity and increases parasympathetic activity.17 The basic causes of physical and mental health-related complaints in perimenopausal women seem to be related to a disorder of the autonomic nervous system, in addition to a decline in estrogen levels.4 Therefore, stretching may help to improve both physical and mental health of perimenopausal women, but evidence in this regard remains unclear. The purpose of this study was to examine the effects of stretching on menopausal and depressive symptoms in middle-aged women.

Sclerostin, coded by SOST, is a secretory protein that is specifically expressed in osteocytes and suppresses osteogenesis by inhibiting WNT signaling. The regulatory mechanism underlying SOST expression remains unclear mainly due to the absence of an adequate human cell model. Thus, we herein attempted to establish a cell model of human dermal fibroblasts in order to investigate the functions of sclerostin. We selected 20 candidate transcription factors (TFs) that induce SOST expression by analyzing gene expression patterns in the human sarcoma cell line, SaOS-2, between differentiation and maintenance cultures using microarrays. An effective set of TFs to induce SOST expression was sought by their viral transduction into fibroblasts, and a combination of four TFs: ATF3, KLF4, PAX4, and SP7, was identified as the most effective inducer of SOST expression. Quantitative PCR demonstrated that the expression levels of SOST in fibroblasts treated with the 4 TFs were 199- and 1439-fold higher than those of the control after 1-week and 4-week cultures, respectively. The level of sclerostin in the conditioned medium, as determined by ELISA, was 21.2pmol/l 4weeks after the transduction of the 4 TFs. Interestingly, the production of Dickkopf1 (DKK1), another secreted inhibitor of WNT signaling, was also increased by transduction of these 4 TFs. Parathyroid hormone (PTH) significantly suppressed the induced SOST by 38% and sclerostin by 82% that of the vehicle. Hypoxia increased the induced SOST by 62% that of normoxia. Furthermore, prostaglandin E2 (PGE2) increased SOST expression levels to 16-fold those of the vehicle. In conclusion, the efficient induction of SOST expression and sclerostin production was achieved in human dermal fibroblasts by the transduction of ATF3, KLF4, PAX4, and SP7, and the induced SOST and sclerostin were regulated by PTH, hypoxia, and PGE2. This model may contribute to elucidating the regulatory mechanisms underlying SOST expression and advancing drug development for metabolic bone diseases.

Aim: Non-invasive steatosis-quantifying methods are required for non-alcoholic fatty liver disease (NAFLD) patients in order to monitor disease severity and assess therapeutic efficacy. Controlled attenuation parameter (CAP) evaluated with vibration-controlled transient elastography can predict the presence of steatosis, but its application to absolute hepatic fat quantitation remains unclear. The aim of this st\udy was to examine whether CAP is correlated with real hepatic fat content in NAFLD patients. Methods Eighty-two NAFLD patients who had undergone percutaneous liver biopsy were enrolled. CAP was measured using FibroScan® just before liver biopsy. The percentage of fat droplet area to hepatocyte area in biopsied specimen was determined morphometrically using computerized optical image analyzing system. The correlation between CAP and liver histology was examined. Results CAP showed an excellent correlation with actual liver fat percentage in the NAFLD patients with body mass index (BMI) of less than 28 kg/m2 (r = 0.579, P

Purpose The aim of this retrospective study was to evaluate a semi-solidifying liquid formula for nasogastric tube (NGT) feeding after oral and maxillofacial surgery. Materials and Methods In total, 42 patients who underwent oral and maxillofacial surgery for malignant tumors, benign tumors, jaw reconstruction, or jaw fractures received postoperative NGT feeding for nutritional control between 2013 and 2019. Of these patients, 21 received a liquid diet (liquid group; administration rate, 100 mL/hour) and 21 received a semi-solidifying liquid formula (semisolid group [SSG]; administration rate, 400 mL/hour; Mermed Plus; Terumo, Tokyo, Japan). We retrospectively evaluated the complications of NGT feeding in both groups. Results During the course of NGT feeding, the incidence of abdominal pain (P = .022), rate of probiotic prescription for diarrhea (P = .012), and Bristol stool form scale score (P = .014) were significantly lower in the SSG than in the liquid group. The maximum defecation frequency per day was also lower in the SSG, although the difference was not significant (P = .069). Conclusions Overall, the semi-solidifying formula was associated with a higher administration rate and a lower incidence of gastrointestinal complications. These findings will help oral and maxillofacial surgeons in the selection of appropriate diets for postoperative NGT feeding.

Backgrounds and study aims: Endoscopic sphincterotomy (ES) is widely accepted as first-line therapy for bile duct stones (BDS). The major long-term pancreaticobiliary complication is BDS recurrence. Whether cholecystectomy should be performed after ES, especially in elderly patients, remains controversial. The aim of this study is to investigate the short-term and long-term outcomes after therapeutic endoscopic retrograde cholangiopancreatography (ERCP) for BDS and to analyze risk factors for pancreaticobiliary complications. We also compared long-term outcomes in patients older and younger than age 80. Patients and methods: A total of 1210 patients who underwent therapeutic ERCP for BDS were retrospectively reviewed to identify risk factors for pancreaticobiliary complications. We divided these patients into two groups: Group Y (

Background and Aim It has been reported that the branched-chain amino acid (BCAA) to tyrosine ratio (BTR) is a useful indicator of liver function and BCAA therapy is associated with a decreased incidence of hepatocellular carcinoma (HCC). However, there has not been sufficient research on the relationship between BTR and the effects of BCAA therapy after initial treatment of HCC. We investigated the impact of BTR and BCAA therapy on survival in patients with HCC. Methods A total of 315 patients with HCC who were treated (n = 66) or not treated (n = 249) with BCAA were enrolled; of these, 66 were selected from each group using propensity score matching. Survival from liver-related mortality was analyzed. Results In patients who did not receive BCAA therapy (n = 249), multivariate analysis for factors associated with survival indicated that low BTR (≤ 4.4) was independently associated with poor prognosis in patients with HCC (hazard ratio, 1.880; 95% confidence interval, 1.125–3.143; P = 0.016). In addition, among patients selected by propensity score matching (n = 132), multivariate analysis indicated that BCAA therapy was independently associated with good prognosis in patients with HCC (hazard ratio, 0.524; 95% confidence interval, 0.282–0.973; P = 0.041). BTR was not significantly associated with survival. Conclusions Intervention involving BCAA therapy improved survival in patients with HCC versus untreated controls, regardless of BTR. In addition, low BTR was associated with poor prognosis in patients who did not receive BCAA therapy.

Background Autoantibody against β 1 -adrenergic receptors (β 1 -AAb) exerts agonist-like action inducing receptor uncoupling and myocardial damage. We attempted to determine the significance of β 1 -AAb in chronic heart failure (CHF) patients who received carvedilol in a substudy of the Japanese Chronic Heart Failure study. Methods and Results In this prospective, randomized, multicenter trial, 117 patients were assigned to 2.5 mg, 5 mg, and 20 mg (n = 38, 36, and 43) carvedilol groups according to the target dose. β 1 -AAb was positive in 51 patients (44%, P) and negative in 66 (56%, N). The percentage increase of left ventricular ejection fraction over 56 weeks (ΔLVEF) was larger in P than in N ( P = .050) and in the high-titer group (H) than in the low-titer group (L; P = .04). Left ventricular (LV) volume decreased to a greater extent in H than in L over 56 weeks. β 1 -AAb titer was significantly correlated with ΔLVEF and the percentage change of LV volume and was an independent predictor of them. No difference was seen in the composite end point (all-cause mortality and hospitalization for cardiovascular diseases or heart failure). However, in patients with dilated cardiomyopathy, it was more common in the 2.5 mg group than in the other groups in N, and it was similar among the 3 groups in P. Conclusions Our data suggest that the presence of β 1 -AAb is associated with favorable response to carvedilol in CHF.

Subjective cognitive complaints (SCC) might be a meaningful indicator of dementia onset or mild cognitive impairment, and identifying the related factors of SCC could contribute to preventing these diseases. However, the relationship between SCC and lifestyle factors remains largely unproven. The purpose of this study was to examine the association of type of sedentary behavior, physical activity, or their combination with SCC among community-dwelling older adults. In 2016, 6677 community-living elderly were recruited to participate in a survey investigating cognition, physical activity, and sedentary behavior. In total, 5328 participants responded to the questionnaire (79.8% valid response rate). SCC was assessed using the National Functional Survey Questionnaire (Kihon checklist). The relationships between SCC and physical activity, sedentary behavior (reading books or newspapers, and television viewing), or combined physical activity and sedentary behavior were examined via multiple logistic regression analysis. The analysis revealed that moderate-to-vigorous physical activity (≥150 min/week) was significantly related with a lower risk of SCC (odds ratio [OR] = 0.85; 95% confidence interval [CI] = 0.74-0.97), and that reading behavior showed a dose-response relationship with SCC (OR for 10-20 min/day = 0.63; 95% CI = 0.53-0.75; OR for 20-30 min/day = 0.59; 95% CI = 0.49-0.71; OR for ≥30 min/day = 0.47; 95% CI = 0.39-0.57). In addition, among those reporting high physical activity and ≥30 min/day for reading time, the OR for SCC was 0.40 (95% CI = 0.32-0.50) compared with the combined group reporting lower physical activity and non-readers. The present study shows that increased physical activity and reading time may be related to a reduced risk for SCC among community-dwelling older adults.

The FIB-4 index is a simple formula using age, aspartate aminotransferase, alanine aminotransferase (ALT) and platelet count to evaluate liver fibrosis. We investigated the ability of the FIB-4 index for hepatocarcinogenesis in hepatitis C virus (HCV) carriers with normal ALT levels. A total of 516 patients with ALT levels persistently at or below 40 IU/L during an observation period of over 3 years were included. Factors associated with the development of HCC were determined. Hepatocellular carcinoma (HCC) developed in 60 of 516 patients (11.6%). The incidence rate of HCC at 5 and 10 years was 2.6% and 17.6%, respectively. When patients were categorized according to the FIB-4 index as ≤ 2.0 (n = 226),2.0 and ≤ 4.0 (n = 169), and4.0 (n = 121), the cumulative incidence of HCC at 5 years was 0.5%, 1.3% and 8.0%, respectively, and 2.8%, 25.6% and 37.1% at 10 years, respectively. Patients with FIB-4 index4.0 were at the highest risk (P0.001). Factors that were significantly associated with HCC in the multivariate analysis were FIB-4 index2.0 (hazard ratio (HR), 7.690), FIB-4 index4.0 (HR, 8.991), α-fetoprotein (AFP)5 ng/mL (HR, 2.742), AFP10 ng/mL (HR, 4.915) and total bilirubin1.2 mg/dL (HR, 2.142). A scoring system for hepatocarcinogenesis that combines the FIB-4 index and AFP predicted patient outcomes with excellent discriminative ability. The FIB-4 index is strongly associated with the risk of HCC in HCV carriers with normal ALT levels.

Duplication of the alimentary tract is a rare congenital malformation that occurs most often in the abdominal region, whereas esophageal duplication cyst develops typically in the thoracic region but occasionally in the neck and abdominal regions. Esophageal duplication cyst is usually diagnosed in early childhood because of symptoms related to bleeding, infection, and displacement of tissue surrounding the lesion. We recently encountered a rare adult case of esophageal duplication cyst in the abdominal esophagus. A 50-year-old man underwent gastroscopy, endoscopic ultrasonography, computed tomography, and magnetic resonance imaging to investigate epigastric pain and dysphagia that started 3 months earlier. Imaging findings suggested esophageal duplication cyst, and the patient underwent laparoscopic resection followed by intraoperative esophagoscopy to reconstruct the esophagus safely and effectively. Histopathological examination of the resected specimen revealed two layers of smooth muscle in the cystic wall, confirming the diagnosis of esophageal duplication cyst.

In recent years, laparoscopy-assisted distal gastrectomy (LADG) has become widely used for the treatment of early gastric cancer. In our hospital, LADG has been performed in 53 patients since it was adopted in November 2006. In the present study, we compared 45 of these LADG patients with T1N0M0 stage IA early gastric cancer and 49 patients who underwent open distal gastrectomy (ODG) during the same period for cancer of the same stage. The compared outcomes included operative time, bleeding loss, and number of lymph node dissections, which reflected the surgical outcomes, as well as the times to first water intake, oral intake, flatus, and bowel movement, and blood test results white blood cell (WBC), C-reactive protein (CRP), which reflected the postoperative course. The length of postoperative hospital stay and complications were also compared. There were no significant differences in operative time or number of lymph node dissections between the groups, although blood loss was significantly lesser with LADG (p

Stafne bone defects (SBDs) are asymptomatic mandibular lingual bone depressions mainly caused by soft tissue inclusions. The most common form of SBDs is posterior; the anterior variant of SBD is relatively uncommon. Although posterior SBD is easily diagnosed by the unique location on radiography, anterior SBD is sometimes misdiagnosed and confused with other pathological entities owing to the location. We report herein a case of simultaneous unilateral anterior and posterior SBDs. In the present case, definitive diagnosis for the anterior mandibular cavity was unclear, as in reported cases. Surgical exploration was thus performed for the lesion in the anterior mandibular cavity. Pathologic examination of the removed tissue showed salivary gland with chronic inflammation. Postoperatively, no functional disturbance has been observed. Management of the posterior SBD was conservative, with radiographic follow-up. To the best of our knowledge, this represents the first report of simultaneous unilateral anterior and posterior SBDs.

Aim Although hyponatremia is associated with a poor prognosis in liver cirrhosis, little is known about the clinical significance of serum sodium concentration in cirrhosis in Japan. This study investigated associations of mortality in Japanese cirrhosis patients taking conventional diuretics with serum sodium concentration and other clinical characteristics. Methods A total of 171 consecutive patients with cirrhosis who were taking diuretic medication were enrolled retrospectively. We determined the prevalence of low serum sodium concentration and searched for associations with age, sex, etiology, complications of cirrhosis, liver function tests and Model for End-Stage Liver Disease (MELD) and MELD-Na scores. The predictive ability of sodium level on mortality was also investigated. Results Median serum sodium concentration was 139 mEq/L (interquartile range, 137-141). Only eight of 171 (4.7%) patients had low serum sodium ( Conclusion Serum sodium concentration below 139 mEq/L and MELD-Na score above 10.5 may be predictive markers for mortality in patients with cirrhosis despite being within normal ranges. These markers may help to better assess and manage the prognosis of patients with cirrhosis in Japan.

Since superior mesenteric vein thrombosis (SMVT) is a relatively rare disease and shows no specific symptom, its diagnosis tends to be delayed. In this report, we present a patient in whom acute appendicitis was complicated by SMVT and portal vein thrombosis (PVT). A definitive diagnosis could be made by abdominal contrast-enhanced CT, and acute appendicitis was surgically treated. Anticoagulant therapy was continued for about half a year after surgery. Abdominal contrast-enhanced CT after discharge showed no recurrence of SMVT or PVT. We consider that acute appendicitis induced SMVT or PVT caused by the effect of inflammation. There is the possibility that these conditions lead to intestinal congestion or necrosis and liver dysfunction; appropriate diagnosis and treatment are necessary.

Aim It has been reported that branched-chain amino acids (BCAA) supplementation can improve nutritional status and reduce liver-related complications in patients with decompensated cirrhosis. BCAA supplementation reportedly reduces the incidence of hepatocellular carcinoma (HCC) in obese cirrhotic patients infected with hepatitis C virus (HCV). We investigated the effects of oral supplementation with BCAA granules on hepatocarcinogenesis in patients with HCV-related cirrhosis using propensity score matching. Methods A total of 60 patients with HCV-related cirrhosis and without history of HCC who were selected by one-to-one matching of propensity scores: 30 patients receiving 12 g/day of BCAA granules for 3 months or more (BCAA group) and 30 being observed without BCAA supplementation (control group). The impact of BCAA supplementation was analyzed on the incidence of HCC. Results The 3- and 5-year rates of HCC development were 13.7% and 13.7% in the BCAA group and 35.1% and 44.5% in the control group, respectively. The BCAA group had a significantly lower rate of HCC than the control group (P = 0.032). Multivariate analysis for factors that were associated with hepatocarcinogenesis indicated that BCAA supplementation was independently associated with a reduced incidence of HCC (hazard ratio 0.131; 95% confidence interval, 0.032–0.530; P = 0.004) along with sex and serum α-fetoprotein. Obesity (body mass index, ≥25 kg/m2) was not significantly associated with an increased incidence of HCC. Conclusion Oral supplementation with BCAA granules is associated with a reduced incidence of HCC in patients with HCV-related cirrhosis regardless of the presence of obesity based on the propensity score analysis.

Background: Core needle biopsy (CNB) and fine needle aspiration cytology (FNAC) are useful methods to diagnose cystic lesions of the breast. The first English article describing the returned cell block method (RCBM: cell block from a Papanicolaou staining smear on a glass slide) was reported by us, and we also reported the usefulness of RCBM for the FNAC-based evaluation of tumors of the breast. In the present study, diagnostic procedures of CNB and FNAC using RCBM for cystic lesions of the breast were studied. Methods: Forty-seven patients with cystic lesions of the breast diagnosed by sonographic examination and sonographically-guided FNAC were evaluated. In all cases, the evaluation of FNAC was performed by Papanicolaou staining smears, and RCBM was added in cases that were difficult to evaluate. The data from CNB (26 cases) and surgery (15 cases) were also evaluated. Results: The accuracy of diagnosing carcinoma of FNAC from Papanicolaou staining smear was 56.2%. The diagnostic accuracy increased to 75% on using RCBM, and the same level of accuracy was found on CNB. In 4 cases, a diagnosis of carcinoma was made by CNB only (2 cases) or FNAC using RCBM only (2 cases). Subsequently, the accuracy increased to 87.5% due to the combination of CNB and FNAC using RCBM. Conclusions: Combined CNB and FNAC using RCBM is effective for the diagnosis of cystic lesions of the breast. Based on this new finding, we propose a procedure to diagnose cystic lesions of the breast by CNB and FNAC using RCBM.

The aim of this study is to evaluate the effect of duration after meals for saliva collections for oral cancer detection using metabolomics. Saliva samples were collected from oral cancer patients (n = 22) and controls (n = 44). Saliva from cancer patients was collected 12 h after dinner, and 1.5 and 3.5 h after breakfast. Control subjects fasted >1.5 h prior to saliva collection. Hydrophilic metabolites were analyzed using capillary electrophoresis mass spectrometry. Levels of 51 metabolites differed significantly in controls vs. oral cancer patients at the 12-h fasting time point (P < 0.05). Fifteen and ten metabolites differed significantly at the 1.5- and 3.5-h time points, respectively. The area of under receiver operating characteristic curve for discriminating oral cancer patients from controls was greatest at the 12-h fasting time point. The collection time after meals affects levels of salivary metabolites for oral cancer screening. The 12-h fasting after dinner time point is optimal. This study contributes to design of saliva collection protocols for metabolomics-based biomarker discovery.

The objective of this study was to explore salivary metabolite biomarkers by profiling both saliva and tumor tissue samples for oral cancer screening. Paired tumor and control tissues were obtained from oral cancer patients and whole unstimulated saliva samples were collected from patients and healthy controls. The comprehensive metabolomic analysis for profiling hydrophilic metabolites was conducted using capillary electrophoresis time-of-flight mass spectrometry. In total, 85 and 45 metabolites showed significant differences between tumor and matched control samples and between salivary samples from oral cancer and controls, respectively (P P