An ectomesenchymal chondromyxoid tumour on the lateral border of the tongue.

Ectomesenchymal chondromyxoid tumour (ECT) is an extremely rare intraoral mesenchymal tumour. Most of these tumours have been identified on the anterior aspect of the dorsal surface of the tongue. ECT is difficult to diagnose because of its rarity. We report a case of ECT arising on the lateral border of the tongue in a 67-year-old woman. The tumour, measuring 20 × 10 mm in size, was surgically removed. Histopathologically, the tumour was composed of small polygonal cells arranged in sheets, with a myxoid or hyalinized stroma. The tumour boundary was clear; however, the tumour showed a multinodular structure expanding along the tongue surface without obvious capsule. Careful examination revealed the tumour nodule to be spreading in a skip lesion-like fashion away from the main part of the tumour in the striated muscle layer. Although there was no evidence of recurrence at 18 months after the surgery, our observations suggest that surgery for ECT resection with a safety margin is more appropriate than enucleation.

Preoperative intra-arterial chemotherapy with docetaxel, cisplatin, and peplomycin combined with intravenous chemotherapy using 5-fluorouracil for oral squamous cell carcinoma.

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.

The correlation between Salter's criteria for avascular necrosis of the femoral head and Kalamchi's prognostic classification following the treatment of developmental dysplasia of the hip.

AIMS: The aim of this study was to evaluate the correlation between Salter's criteria and Kalamchi's classification of avascular necrosis in patients treated for developmental dysphasia of the hip (DDH). PATIENTS AND METHODS: The study involved a retrospective analysis of 123 patients (123 hips) with DDH treated by operative and non-operative reduction before the age of two years, with a minimum follow-up of ten years. Salter's criteria (S1 to S4) were determined from radiographs obtained at one to two years post-reduction, whilst the Kalamchi grade was determined from radiographs obtained at ten or more years of age. Early post-reduction radiographs were also used to evaluate the centre-head distance discrepancy (CHDD) and the occurrence of a dome-shaped deformity of the proximal femoral metaphysis (D-shaped metaphysis). The prognosis was described as good (Kalamchi grade K0 or KI), fair (Kalamchi grade KII) or poor (Kalamchi grade KIII or KIV) for analysis and correlation with the early Salter criteria, CHDD and D-shaped metaphysis. RESULTS: S1 and S2 criteria were predictive of a poor prognosis. The outcome following S3, S4 and S3 + S4 varied; 18 (40%) had a good prognosis, 17 (38%) a fair prognosis and ten (22%) a poor prognosis. A CHDD ≥ 10% and a D-shaped metaphysis were also predictive of a poor prognosis. CONCLUSION: The Salter criteria were predictive of the Kalamchi grade of avascular necrosis in patients with DDH aged ten or more years after reduction of the hip. Cite this article: Bone Joint J 2017;99-B:1115-20.

The age, breed and sex pattern of diagnosis for veterinary care in insured cats in Japan.

OBJECTIVES: To estimate the annual prevalence of different diagnostic categories by age, breed and sex in insured cats in Japan for which veterinary care claims had been made, and to identify if there is a pattern in these host factors. MATERIALS AND METHODS: Data from 48,187 cats insured for veterinary care in Japan in the period from April 2012 to March 2013 comprising 26,003 males and 22,184 females were analysed to calculate the annual prevalence of 18 diagnostic categories of disease by age, breed and sex. RESULTS: The prevalence was highest for urinary system disorders (12·2% for males and 10·0% for females), followed by digestive disorders (11·6% for males and 10·7% for females) and dermatological diseases (8·7% for males and 9·0% for females). The male cats had a higher prevalence than female cats for most diagnostic categories. The prevalence of cardiovascular, urinary, endocrine and neoplastic disorders increased with age; infectious and parasitic diseases had high prevalence at young ages, and the prevalence of respiratory, musculoskeletal disorders and injuries had bimodal peaks. Dermatological disorders had a high prevalence at all ages. A large variation in prevalence was observed between breeds for otic, dermatological, dental and cardiovascular disorders. CLINICAL SIGNIFICANCE: The findings can be used to increase awareness of patterns of health disorders in different categories of cat.

Measurement of residual platelet thrombogenicity under arterial shear conditions in cerebrovascular disease patients receiving antiplatelet therapy.

UNLABELLED: Essentials A consensus methodology for assessing the effects of antiplatelet agents has not been established. Measuring platelet thrombus formation (PTF) for evaluating antiplatelet effects was assessed. PTF differentially reflected antiplatelet effects compared to other tests. PTF may be associated with the severity of carotid or intracranial arterial stenosis. Click to hear a presentation on platelet function testing in the clinic by Gresele and colleagues SUMMARY: Background A consensus methodology for assessing the effects of antiplatelet agents has not been established. Objective We investigated the usefulness of directly measuring platelet thrombus formation (PTF) using a microchip-based flow chamber system for evaluating antiplatelet therapy. Patients/Methods Platelet thrombus formation in the whole blood of 94 patients with ischemic cerebrovascular disease treated with clopidogrel and/or aspirin was measured in a flow chamber system at a shear rate of 1500 s(-1) and was compared with the results of assays for agonist-induced platelet aggregability, phosphorylation of vasodilator-stimulated phosphoprotein, platelet p-selectin expression (PS), and platelet-monocyte complexes. Results In all patients tested, area under the flow pressure curve (AUC10), which represents platelet thrombogenicity, showed weak correlation with platelet aggregation induced by either adenosine diphosphate or collagen. In addition, AUC10 was lower in patients treated with dual antiplatelet therapy (median 79.4) compared with patients treated with aspirin or clopidogrel alone (217.7 and 301.0, respectively), whereas the parameters evaluated by the other assays did not reflect the combined treatment efficacy. In clopidogrel monotherapy patients, AUC10 was associated with the severity of arterial stenosis (R(2) = 0.127, ß = 1.25), and AUC10 and PS were higher in patients with severe carotid or intracranial arterial stenosis than in those with mild stenosis. Conclusions Platelet thrombus formation measurement using a flow-chamber system was useful for evaluating the efficacy of treatment with aspirin and clopidogrel, both alone and in combination. The present findings indicate that high residual platelet thrombogenicity in patients treated with clopidogrel may be associated with the severity of carotid or intracranial arterial stenosis.

Facilitation of bone resorption activities in synovial lavage fluid patients with mandibular condyle fractures.

The aim of this study was to investigate the bone resorption effect of the mediators delivered in joint cavity of patients with mandibular condyle fractures by detecting osteoclast markers using cellular biochemistry methods, and by analysing bone resorption activities via inducing osteoclast differentiation of the infiltrated cells from arthrocentesis. Sixteen joints in 10 patients with mandibular condyle fractures were evaluated. The control group consisted of synovial fluid (SF) samples from seven joints of four volunteers who had no clinical signs or symptoms involving the temporomandibular joint (TMJ) or disc displacement. We collected SF cells from all patients during therapeutic arthrocentesis. The infiltrating cells from TMJ SF were cultured, differentiated into tartrate-resistant acid phosphatase (TRAP)-positive osteoclast-like cells and examined bone resorption activities. We also investigated factors related to osteoclast induction of SF, using ELISA procedures. Osteoclast-like cells were induced from the SF cells obtained from all patients with condylar fractures. These multinucleated giant cells were positive for TRAP and actin, and had the ability to absorb dentin slices. The levels of macrophage colony-stimulating factor (M-CSF), prostaglandin E2 (PGE2), soluble form of receptor activator of nuclear factor kappa-B ligand (sRANKL) and osteoprotegerin (OPG), in SF samples from the patients, were significantly higher than in the controls. These findings indicate that bone resorption activities in SF from patients with mandibular condyle fractures were upregulated and may participate in the pathogenesis and wound healing.

Relationship between CT features and high preoperative serum carcinoembryonic antigen levels in early-stage lung adenocarcinoma.

AIM: To assess the relationship between thin-section computed tomography (CT) features of primary tumour and high preoperative serum carcinoembryonic antigen (CEA) levels that reportedly suggest poor prognoses in early-stage lung adenocarcinoma. MATERIALS AND METHODS: Two hundred and seventy-five consecutive patients who underwent resection of pathological stage I (T1-2aN0M0) adenocarcinomas with a maximum diameter of ≤ 3 cm (144 men, 131 women; mean age 67.8 years) were enrolled. CT features of the primary tumours and clinical characteristics of these patients were statistically evaluated to identify the factors associated with high serum CEA levels (>5 ng/ml). RESULTS: Eighty-one patients (29.5%) had high serum CEA levels. In univariate analysis, lower ground-glass opacity ratio (p < 0.001), lower tumour shadow disappearance rate (TDR: the ratio of tumour area in mediastinal window to that of lung window, p < 0.001), presence of notch (p = 0.015), and coexistence with bullae or honeycomb cysts (p < 0.001) were observed more frequently in the group with high serum CEA levels than that of the group with normal levels. TDR [odds ratio (OR) 0.984; 95% confidence interval (CI): 0.976-0.993; p < 0.001] and coexistence with bullae or honeycomb cysts (OR = 3.08; 95% CI: 1.55-6.12; p = 0.001) remained significant, even after adjusting patients' age, gender, and smoking status. CONCLUSIONS: Adenocarcinomas with lower TDR and coexisting with bullae or honeycomb cysts are associated with high preoperative serum CEA levels. Although some CEA elevations may be due to benign pulmonary diseases, such tumours are suspected to have poor prognoses, even for early-stage diseases.

Factors affecting variability in home blood pressure in patients with type 2 diabetes: post hoc analysis of a cross-sectional multicenter study.

Recent studies have shown that variability in home blood pressure has an important role in the progression of organ damage. The objective of this study was to investigate the factors that affect variability in home blood pressure in patients with type 2 diabetes. We assessed the relationship between home blood pressure variability, defined as coefficient of variation of mean of triplicate morning and evening blood pressure for 14 consecutive days, and various factors using univariate and multivariate linear regression analyses in 1114 patients with type 2 diabetes. Age (ß=0.149, P<0.001), female sex (ß=0.125, P=0.010), duration of diabetes mellitus (ß=0.103, P=0.005), heart rate (ß=0.136, P<0.001), current smoker (ß=0.118, P=0.005), white-coat hypertension (ß=0.136, P=0.002) and treatment with calcium channel blockers (ß=-0.094, P=0.024) were independently associated with coefficient of variation of morning systolic blood pressure. Our findings implicate that factors that might be intervened such as heart rate, smoking status, use of antihypertensive medication in addition to age, sex and duration of diabetes mellitus are associated with variability in home blood pressure in patients with type 2 diabetes.

Diagnostic performance of plasma biomarkers in patients with acute intestinal ischaemia.

BACKGROUND: The aim of this study was to evaluate the use of intestinal fatty acid binding protein (I-FABP) and traditional biomarkers in the early diagnosis of acute intestinal ischaemia of different causes. METHODS: I-FABP, white blood cell (WBC) count, C-reactive protein, base deficit, lactate, lactate dehydrogenase, aspartate aminotransferase, creatine kinase and D-dimer were measured prospectively in consecutive patients suspected of having acute intestinal ischaemia. Biomarker levels were compared in patients with vascular and non-vascular ischaemia. RESULTS: Two hundred and eight patients with a clinical suspicion of acute intestinal ischaemia were enrolled. Vascular intestinal ischaemia was diagnosed in 24 patients (11·5 per cent), non-vascular ischaemia in 62 (29·8 per cent) and non-ischaemic disease in 122 (58·7 per cent). The levels of most biomarkers (except WBC count and creatine kinase) were significantly higher in the vascular ischaemia group than in the other groups (P < 0·010). However, none of the biomarker levels differed between patients with non-vascular intestinal ischaemia and those with non-ischaemic disease. Receiver operating characteristic (ROC) curve analysis suggested that I-FABP was best at diagnosing vascular intestinal ischaemia (area under the curve 0·88). CONCLUSION: Serum biomarkers may be useful in the diagnosis of vascular, but not non-vascular, intestinal ischaemia. Among them, I-FABP shows promise for detecting vascular ischaemia.

Hiatal hernia following total gastrectomy with Roux-en-Y reconstruction.

Hiatal hernias after total gastrectomy for advanced gastric cancer are very rare. We review a case of a 44-year-old male who presented with dyspnea and chest pain 2 days after total gastrectomy, lower esophagectomy, and splenectomy with retrocolic Roux-en-Y reconstruction approached by a left thoracoabdominal incision for gastric cancer at the cardia. Plain and cross-sectional imaging identified a large hiatal hernia protruding into the right thorax containing left-sided transverse colon and small intestine. Our patient underwent a laparotomy, and after hernia reduction the hiatal defect was repaired by direct suturing. He experienced anastomotic leakage and right pyothorax, but recovered. The potential cause is discussed here and the published literature on this rare complication is reviewed briefly.

TWEAK/Fn14 pathway promotes a T helper 2-type chronic colitis with fibrosis in mice.

Tumor necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK), a TNF superfamily member, induces damage of the epithelial cells (ECs) and production of inflammatory mediaters through its receptor Fn14 in a model of acute colitis. In our current study of chronic colitis induced by repeated rectal injection of a hapten, we found that inflammation, fibrosis, and T helper 2 (Th2)-type immunity were significantly reduced in Fn14 gene knockout (KO) mice when compared with wild-type (WT) control mice. Expression of thymic stromal lymphopoietin (TSLP) was lower in Fn14 KO colon ECs than in WT ECs. TWEAK potentiates the induction of TSLP by interleukin-13 (IL-13) in colon explants from WT but not in Fn14 KO tissue. TSLP receptor KO mice exhibit milder chronic colitis, similar to that in Fn14 KO mice. TWEAK and IL-13 synergistically promote fibroblast proliferation. Thus we propose an IL-13-TWEAK/Fn14-TSLP axis as a key mechanism underlying chronic colitis with fibrosis.

Inflammatory histopathogenesis of nasopalatine duct cyst: a clinicopathological study of 41 cases.

OBJECTIVE: The aim of this study is to characterize immunohistochemical profiles of lining epithelia of nasopalatine duct cyst (NPC) as well as to correlate those findings with their clinicopathological features to understand the histopathogenesis of NPC. MATERIALS AND METHODS: Forty-one surgical specimens from NPC were examined for clinical profiles and expression of keratin-7, 13, MUC-1, and P63 by immunohistochemistry, compared to radicular cyst (RC) and maxillary sinusitis. RESULTS: Nasopalatine duct cyst was clinically characterized by male predominant occurrence: 44% of the cases involved tooth roots, and 70% with inflammatory backgrounds. Lining epithelia of NPCs without daughter cysts were immunohistochemically distinguished into three layers: a keratin 7-positive (+) ciliated cell layer in the surface, a keratin-13+ middle layer, and a MUC-1+/P63+ lower half, indicating that they were not respiratory epithelia, and the same layering pattern was observed in RC. However, those immunolocalization patterns of the main cyst lining with daughter cyst were exactly the same as those of daughter cyst linings as well as duct epithelia of mucous glands. CONCLUSIONS: Two possible histopathogenesis of NPC were clarified: one was inflammatory cyst like RC and the other was salivary duct cyst-like mucocele.

Nasu-Hakola disease with a splicing mutation of TREM2 in a Japanese family.

BACKGROUND: Nasu-Hakola disease (NHD) is a rare autosomal recessive disorder, characterized by a combination of progressive presenile dementia and formation of multifocal bone cysts, caused by genetic mutations of DAP12 and TREM2, which constitute a receptor/adapter signaling complex expressed on osteoclasts, dendritic cells, macrophages, and microglia. No Japanese patients with TREM2 mutations have been reported previously. METHODS: We reported three siblings affected with NHD in a Japanese family. Amongst them, two died of NHD during the fourth decade of life. The analysis of genomic DNA, cDNA cloning, and western blot of lymphocyte proteins was performed on samples of the living patient. The transcriptome was studied in the autopsied brain of one patient. RESULTS: We identified a homozygous conversion of a single nucleotide T to C at the second position of intron 3 in the splice-donor consensus site (c.482+2T>C) of the TREM2 gene, resulting in exon 3 skipping and aberrant expression of truncated proteins. We identified 136 upregulated genes involved in inflammatory response and immune cell trafficking and 188 downregulated genes including a battery of GABA receptor subunits and synaptic proteins in the patient's brain. CONCLUSIONS: This is the first report of a Japanese NHD family caused by a splicing mutation of TREM2 that induces both neuroinflammation and neurodegeneration.

Low serum bilirubin concentration in haemodialysis patients with Type 2 diabetes.

AIMS: Previous studies have implicated reduced serum bilirubin concentrations in the development of cardiovascular disease. The aim of this study was to examine whether bilirubin may explain the high incidence of vascular complications in haemodialysis patients with Type 2 diabetes. METHODS: We compared serum bilirubin concentrations, as well as other known aetiological risk factors for cardiovascular disease, in 206 Type 2 diabetes patients on haemodialysis with those in 741 Type 2 diabetes patients not receiving haemodialysis, and evaluated the association between serum bilirubin concentration and cardiovascular disease incidence. RESULTS: Incidences of cardiovascular disease and systolic blood pressure were higher; however, BMI and serum total cholesterol were lower in haemodialysis patients compared with those in patients without haemodialysis. Serum total (0.30 ± 0.10 vs. 0.74 ± 0.26 mg/dl, 0.005 ± 0.002 vs. 0.013 ± 0.004 mmol/l, P < 0.0001) and indirect (0.17 ± 0.08 vs. 0.70 ± 0.23 mg/dl, 0.003 ± 0.001 vs. 0.012 ± 0.004 mmol/l, P < 0.0001) bilirubin were lower in haemodialysis patients compared with those in patients without haemodialysis. Stepwise regression analysis demonstrated that age (ß = 0.109, F = 5.959, P < 0.05), duration of diabetes (ß = -0.112, F = 6.048, P < 0.05), sex (ß = -0.123, F = 8.623, P < 0.05), cardiovascular disease events (ß = -0.099, F = 5.131, P < 0.05) and presence of haemodialysis (ß = -0.626, F = 201.727, P < 0.01) were independent factors for serum total bilirubin. Logistic regression demonstrated that age (OR 1.089, 95% CI 1.044-1.136; P < 0.0001), duration of diabetes (OR 1.029, 95% CI 1.001-1.059; P = 0.0423), body mass index (OR 1.115, 95% CI 1.001-1.242; P = 0.0487), habit of smoking (OR 2.445, 95% CI 1.046-5.716; P = 0.0391) and serum total bilirubin (OR 0.192, 95% CI 0.037-0.989; P = 0.0484) were independent factors for cardiovascular disease events. CONCLUSIONS: Low serum bilirubin concentration could be one of the important factors for the high incidence of cardiovascular disease in Type 2 diabetes patients receiving haemodialysis.

Complication of adenoid cystic carcinoma and sialolithiasis in the submandibular gland: report of a case and its etiological background.

The authors report a case of adenoid cystic carcinoma (ACC) complicated with sialolithiasis of the submandibular gland. The patient was a 43-year-old female with a history of papillotubular carcinoma of the breast almost at the same time. She had noticed a swelling in her sublingual area for 10 years, which was later diagnosed by her dentist to be due to a sialolith in the left submandibular gland. After several years of observation, the patient was referred to have her left submandibular gland, containing the stone, surgically removed with a diagnosis of atrophic sialadenitis. Histopathologically, the submandibular gland was extensively replaced with fibrous granulation tissue, in which there were small but invasive foci of ACC. The present case indicates that ACC could arise in the background of chronic sialadenitis. It is suggested that long-standing sialadenitis cases should be carefully examined to exclude suspicion of malignancy before surgery.

Cerebral oxygenation in the beach chair position before and during general anesthesia.

AIM: Ischemic brain damage related to the beach chair position is a matter of concern. The current study was designed to evaluate whether the beach chair position before and during general anesthesia differentially induces changes in cerebral oxygenation as determined by near-infrared spectroscopy (NIRS) in surgical patients. METHODS: We evaluated brain tissue oxygen index (TOI) values using the NIRS monitor NIRO-200TM in the beach chair position the day before and during general anesthesia. Thirty patients with normal preoperative TOI values undergoing shoulder surgery were enrolled. The initial TOI measurement in the supine position after 10 min rest or 10 min after tracheal intubation was followed by measurements after 5 min each in the 30-degree and subsequently 60-degree head-up tilt positions. During general anesthesia, patients were mechanically ventilated to obtain normocapnia under inhalation of 1.5% sevoflurane in 50% oxygen. Mean blood pressure (MAP) was measured non-invasively in the arm at heart level and was maintained above 60 mmHg with phenylephrine. RESULTS: Preoperative TOI values and preoperative MAP were within the normal range in the study population. MAP decreased upon anesthesia but did not further change when the patient was placed in the 30- and 60-degree head-up tilt positions. Heart rate also decreased upon anesthesia. However, TOI values did not change with induction of general anesthesia or placement of the patients in the beach chair position. CONCLUSION: Under general anesthesia, the beach chair position does not alter cerebral oxygenation in patients showing normal preoperative cerebral TOI values.

A novel nonsecosteroidal VDR agonist (CH5036249) exhibits efficacy in a spontaneous benign prostatic hyperplasia beagle model.

To date, there have been no reports showing the efficacy of nonsecosteroidal vitamin D receptor (VDR) agonists in a benign prostatic hyperplasia (BPH) animal model. To examine the efficacy of CH5036249, a novel nonsecosteroidal VDR agonist, we orally administered the compound at 0.03 microg/kg to a beagle model with spontaneous BPH. Prostate volume was checked by rectal ultrasonic probe periodically during 11 months of administration and the prostate tissues histologically examined. CH5036249 inhibited prostate growth in two out of three dogs compared with vehicle-treated dogs. In the prostate specimens, substantial atrophy of the epithelium was observed in all dogs administered CH5036249. At the dose given, serum calcium levels slightly increased in the CH5036249-treated dogs but stayed within a normal range. We next examined the cell growth inhibition of CH5036249 using human prostate stromal cells and found the cell growth inhibitory activity of CH5036249 to be comparable to that of 1alpha,25(OH)2D3. The bioavailability from oral administration in rats was 95.1% with a t1/2 of 17.6 h. Both micro-AMES and micronucleus tests were negative. Although the results are still preliminary, we consider the novel nonsecosteroidal VDR agonist CH5036249 to be a possible new drug candidate for the treatment of BPH in humans.

Reduction of type II taste cells correlates with taste dysfunction after X-ray irradiation in mice.

BACKGROUND: Taste dysfunction that develops after radiotherapy for head and neck cancer impairs patients' quality of life. Although taste cells have been shown to degenerate after exposure to X-ray irradiation, the alteration in taste cell population is unclear. This study investigated the histopathological change of taste bud structure and the taste cell population in X-ray irradiated mice. METHODS: The head and neck region of C57BL/6J male mice was exposed to a single 15 Gy dose of X-ray irradiation and a chronological histopathological analysis of the circumvallate papilla was performed. Preference for sweet taste was measured using the two-bottle preference method. RESULTS: The histological analysis of the circumvallate papilla revealed that the basal cells had almost disappeared, but that there was not clear change in the spindle-shaped taste cells on day 4 after irradiation. The number of taste cells had decreased on day 8, and then remained unchanged until day 20, after which they increased and recovered to their original number by day 24. There was a more marked decrease in the number of alpha-gustducin-positive type II taste cells than in the number of serotonin-positive type III taste cells. Preference for sweet taste measured by the two-bottle preference method was decreased in parallel with taste cell number. CONCLUSION: These findings suggest that X-ray irradiation disrupts the basal cells, resulting in a decrease of the number of taste cells, particularly type II taste cells, which may be the cause of radiotherapy-induced taste dysfunction.