Kazuya Inoue

Overexpression of extracellular-signal regulated kinases on oral squamous cell carcinoma

Mitogen-activated protein kinases (MAPKs) consist of major three subfamilies, extracellular-signal regulated kinases (ERK MAPKs), the c-Jun N-terminal kinases/stress activated protein kinases (JNK MAPKs/SAP MAPKs), and p38 MAPKs. ERK MAPKs pathway is one of the most important pathways for cell proliferation. ERK MAPKs are located at downstream of a lot of growth factors (epidermal growth factor (EGF), nerve growth factor (NGF), platelet-derived growth factor (PDGF), etc.), the overexpressions and activation of which are frequently detected on a number of cancers including oral squamous cell carcinoma (OSCC). These data indicate that overexpression and activation of ERK MAPKs play an important role in cancer progression. On the contrary, JNK MAPKs are possible regulators of cell death induced by chemotherapeutic agents. p38 MAPKs are activated by pro-inflammatory cytokines and inflammatory drugs (non-steroidal anti-inflammatory drug), which are known to suppress cancer growth. These findings imply that each MAPKs can be molecular targets for cancer therapy in OSCC and its investigation is very important things in OSCC.

Bone marrow stimulation at the footprint of arthroscopic surface-holding repair advances cuff repair integrity

BACKGROUND Bone marrow stimulation (BMS) at the footprint of arthroscopic rotator cuff repair has not been fully evaluated according to the preoperative tear size and surgical technique. In this study, we investigated the effect of BMS on cuff repair integrity after an arthroscopic surface-holding (ASH) repair. MATERIALS AND METHODS A total of 111 patients (mean age, 64.5 years) with chronic rotator cuff tears who underwent treatment by the ASH method with BMS by drilling of multiple holes at the footprint (67 shoulders) or without BMS (44 shoulders) were studied, and all patients were observed prospectively. Sugayas classification was used to evaluate cuff integrity by postoperative magnetic resonance imaging, with types IV and V classified as rotator cuff retears. RESULTS The mean scores for cuff integrity were 2.2 ± 0.2 and 1.7 ± 0.2 in the non-BMS and BMS groups, respectively. The mean scores were similar between the 2 groups for medium tears; however, scores for large-massive tears were significantly lower in the BMS group. The overall retear rate was 23.9% in the non-BMS group and 9.1% in the BMS group, and the distribution of repair types differed significantly. For large-massive tears, the retear rate was much higher in the non-BMS group (28.6%) than in the BMS group (4.5%), although the rates for medium tears were comparable between the 2 groups. CONCLUSIONS These findings demonstrate that applying BMS to the footprint during ASH repair results in improved cuff repair integrity, particularly in large-massive tears, and suggest the importance of biologic treatment for rotator cuff healing after arthroscopic rotator cuff repair.

Analysis of trabecular bone microstructure in osteoporotic femoral heads in human patients: in vivo study using multidetector row computed tomography

BackgroundLag screw position is very important in the treatment of intertrochanteric femoral fracture to prevent complications such as screw cut-out. Current studies recommend central or inferior placement of the lag screw on the anteroposterior radiograph, and central placement on the lateral radiographs. These reports are based on radiographic evaluation, but few studies have investigated the importance of bone quality at the site of lag screw placement. In this study, we used multidetector row computed tomography (MDCT) to perform in vivo evaluation of the bone microstructure of the femoral head in patients with intertrochanteric femoral fractures.MethodsThis study was approved by the Ethics Committee of Okanami General Hospital. MDCT images were obtained in our hospital from ten patients who had sustained intertrochanteric femoral fracture. Patients who needed computed tomography to confirm fracture morphology were included. We defined six areas as regions of interest (ROI): ROI 1–3 were defined as the femoral head apex area, and ROI 4–6 were defined as the femoral neck area. Trabecular microstructure parameters, including mean bone volume to total volume (BV/TV), trabecular thickness (Tb.Th), trabecular separation (Tb.Sp), and structure model index (SMI), were evaluated with bone analysis software (TRI/3D-BON). Statistical analyses were performed using EZR software; each parameter among the ROIs was statistically evaluated by analysis of variance (ANOVA) and Tukey’s test. Statistical significance was established at p < 0.05.ResultsIn the apical area, all parameters indicated that ROI 1 (superior) had the highest bone quality and ROI 2 (central) was higher in bone quality than ROI 3 (inferior). In the femoral neck, all parameters indicated that bone quality was significantly greater in ROI 6 (inferior) than ROI 5 (central).Discussion and ConclusionsWe could evaluate bone quality with clinical MDCT in vivo. Bone quality in the central area of the femoral head apical was greater than in the inferior area, and bone quality in the inferior area of the femoral neck was greater than in the central area. Recognizing which area of femoral head has greater bone quality may lead to a better clinical result in treating intertrochanteric femoral fracture.

Efficacy of FDG-PET for defining gross tumor volume of head and neck cancer.

We analyzed the data for 53 patients with histologically proven primary squamous cell carcinoma of the head and neck treated with radiotherapy between February 2006 and August 2009. All patients underwent contrast-enhanced (CE)-CT and 18F-fluorodeoxyglucose (FDG)-PET before radiation therapy planning (RTP) to define the gross tumor volume (GTV). The PET-based GTV (PET-GTV) for RTP was defined using both CE-CT images and FDG-PET images. The CE-CT tumor volume corresponding to a FDG-PET image was regarded as the PET-GTV. The CE-CT-based GTV (CT-GTV) for RTP was defined using CE-CT images alone. Additionally, CT-GTV delineation and PET-GTV delineation were performed by four radiation oncologists independently in 19 cases. All four oncologists did both methods. Of these, PET-GTV delineation was successfully performed in all 19 cases, but CT-GTV delineation was not performed in 4 cases. In the other 15 cases, the mean CT-GTV was larger than the PET-GTV in 10 cases, and the standard deviation of the CT-GTV was larger than that of the PET-GTV in 10 cases. Sensitivity of PET-GTV for identifying the primary tumor was 96%, but that of CT-GTV was 81% (P < 0.01). In patients with oropharyngeal cancer and tongue cancer, the sensitivity of CT-GTV was 63% and 71%, respectively. When both the primary lesions and the lymph nodes were evaluated for RTP, PET-GTV differed from CT-GTV in 19 cases (36%). These results suggested that FDG-PET is effective for defining GTV in RTP for squamous cell carcinoma of the head and neck, and PET-GTV evaluated by both CE-CT and FDG-PET images is preferable to CT-GTV by CE-CT alone.

Changes in expression of p38 mitogen‐activated protein kinase in the dorsal motor nucleus of the vagus nerve and hypoglossal nucleus after axotomy in adult rats

Mitogen‐activated protein (MAP) kinase cascades are activated in response to various extracellular stimuli. P38 MAP kinase is one of the MAP kinase family and is activated by proinflammatory cytokines and environmental stresses. Activating transcription factor‐2 (ATF‐2) is one of the targets for p38 MAP kinase. To obtain information on the role of the p38 MAP kinase in the neurons and glial cells after axotomy, we investigated changes of expression of p38 MAP kinase, MAP kinase kinase (MKK) 3, MKK4, MKK6 and ATF‐2 in the dorsal motor nucleus of the vagus nerve and the hypoglossal nucleus following axotomy in rats using in situ hybridization and immunohistochemical techniques. Expression of p38 MAP kinase mRNA was observed in the neurons in control rats and showed no remarkable changes after axotomy in both nuclei. On the other hand, expression of p38 MAP kinase mRNA was observed in the perineuronal microglias after axotomy. The expression of p38 MAP kinase, activated p38 MAP kinase, MKK3 and ATF‐2 were immunohistochemically observed in neurons of control rats in both nuclei. After axotomy, the expression of p38 MAP kinase, active and inactive, and ATF‐2 in neurons were reduced in both nuclei, while expression of mRNA of p38 MAP kinase showed no reduction in neurons. These findings indicate that p38 MAP kinase is functionally regulated not by synthesis but by phosphorylation and regulates the activation of ATF‐2 in neurons, and this cascade plays some role in retrograde neuronal reactions. Moreover, perineuronal microglial cells showed strong expression of p38 MAP kinase, active and inactive, after axotomy in both nuclei. These findings suggest that p38 MAP kinase is related to microglial cell reactions after axotomy.

Humeral bone resorption after anatomic shoulder arthroplasty using an uncemented stem

BACKGROUND Bone resorption around the femoral stem after total hip arthroplasty is a well-known phenomenon. However, only a few studies have evaluated bone resorption after shoulder arthroplasty. This study investigated the prevalence of humeral bone resorption after different shoulder arthroplasty procedures. METHODS The study included 147 shoulders that underwent total shoulder arthroplasty (TSA) or humeral head replacement (HHR) with an uncemented humeral stem from November 2008 to May 2015 and were monitored for more than 1 year. The prevalence of humeral bone resorption and risk factors were investigated. RESULTS The most advanced grade of bone resorption, grade 0, occurred in 21 shoulders (14.3%). Grade 1 bone resorption occurred in 10 (6.8%), grade 2 in 28 (19.0%), grade 3 in 61 (41.5%), and grade 4 in 27 (18.4%). High occurrence of bone absorption was observed in zones 1, 2, and 7. Grade 4 bone resorption did not occur in zones 3 and 5. HHR, on-growth type stem coating, and occupation ratio were significant independent risk factors for grade ≥3 bone resorption, whereas female sex and HHR were significant independent risk factors for grade 4. CONCLUSION Bone resorption was observed in 126 shoulders (85.7%), and full-thickness cortical bone resorption occurred in 27 shoulders (18.4%). Bone resorption was frequently observed at the greater tuberosity, lateral diaphysis, and calcar region (zones 1, 2, and 7). Significant risk factors included female sex, HHR with rotator cuff reconstruction, on-growth type stem coating, and high occupation ratio of the implant.

In vivo microstructural analysis of the humeral greater tuberosity in patients with rotator cuff tears using multidetector row computed tomography

BackgroundIn arthroscopic surgery, the suture anchor technique has become popular for rotator cuff repair. Preoperative evaluation of the bone microstructure is of utmost importance because, especially in elderly patients, osteoporotic changes may cause anchor pullout, which results in failure of rotator cuff repair. Many groups have reported humeral microstructural analysis; however, most studies were experiments using porcine specimens or human cadavers. In this study, we used multidetector row computed tomography to successfully perform in vivo evaluation of the bone microstructure of the humeral greater tuberosity in patients with rotator cuff tears.MethodsTen patients were examined. Regions of interest were defined in six quadrants of the greater tuberosity (medial, lateral, and far lateral rows of the anterior and posterior areas). The local bone mineral density and the trabecular microstructural parameters, including the mean bone volume to total volume (BV/TV), trabecular thickness, trabecular separation, and structure model index (SMI), were measured using bone analysis software.ResultsThe BV/TV of the posteromedial region was highest and the SMI of the posteromedial region was lowest. These findings suggest that the bone quality of the posteromedial portion is the highest within the greater tuberosity.ConclusionBecause the bone quality may be correlated with the pullout strength of suture anchors, our method can help to understand the individual and regional variance in bone quality and may lead to the creation of personalized surgical protocols.

Biceps-Related Physical Findings Are Useful to Prevent Misdiagnosis of Cervical Spondylotic Amyotrophy as a Rotator Cuff Tear

Study Design Case–control study. Purpose The aim of the present study was to identify physical findings useful for differentiating between cervical spondylotic amyotrophy (CSA) and rotator cuff tears to prevent the misdiagnosis of CSA as a rotator cuff tear. Overview of Literature CSA and rotator cuff tears are often confused among patients presenting with difficulty in shoulder elevation. Methods Twenty-five patients with CSA and 27 with rotator cuff tears were enrolled. We included five physical findings specific to CSA that were observed in both CSA and rotator cuff tear patients. The findings were as follows: (1) weakness of the deltoid muscle, (2) weakness of the biceps muscle, (3) atrophy of the deltoid muscle, (4) atrophy of the biceps muscle, and (5) swallow-tail sign (assessment of the posterior fibers of the deltoid). Results Among 25 CSA patients, 10 (40.0%) were misdiagnosed with a rotator cuff tear on initial diagnosis. The sensitivity and specificity of each physical finding were as follows: (1) deltoid weakness (sensitivity, 92.0%; specificity, 55.6%), (2) biceps weakness (sensitivity, 80.0%; specificity, 100%), (3) deltoid atrophy (sensitivity, 96.0%; specificity, 77.8%), (4) biceps atrophy (sensitivity, 88.8%; specificity, 92.6%), and (5) swallow-tail sign (sensitivity, 56.0%; specificity, 74.1%). There were statistically significant differences in each physical finding. Conclusions CSA is likely to be misdiagnosed as a rotator cuff tear; however, weakness and atrophy of the biceps are useful findings for differentiating between CSA and rotator cuff tears to prevent misdiagnosis.

Modifying oxygen tension affects bone marrow stromal cell osteogenesis for regenerative medicine

AIM To establish a hypoxic environment for promoting osteogenesis in rat marrow stromal cells (MSCs) using osteogenic matrix cell sheets (OMCSs). METHODS Rat MSCs were cultured in osteogenic media under one of four varying oxygen conditions: Normoxia (21% O2) for 14 d (NN), normoxia for 7 d followed by hypoxia (5% O2) for 7 d (NH), hypoxia for 7 d followed by normoxia for 7 d (HN), or hypoxia for 14 d (HH). Osteogenesis was evaluated by observing changes in cell morphology and calcium deposition, and by measuring osteocalcin secretion (ELISA) and calcium content. In vivo syngeneic transplantation using OMCSs and β-tricalcium phosphate discs, preconditioned under NN or HN conditions, was also evaluated by histology, calcium content measurements, and real-time quantitative PCR. RESULTS In the NN and HN groups, differentiated, cuboidal-shaped cells were readily observed, along with calcium deposits. In the HN group, the levels of secreted osteocalcin increased rapidly from day 10 as compared with the other groups, and plateaued at day 12 (P < 0.05). At day 14, the HN group showed the highest amount of calcium deposition. In vivo, the HN group showed histologically prominent new bone formation, increased calcium deposition, and higher collagen type I messenger RNA expression as compared with the NN group. CONCLUSION The results of this study indicate that modifying oxygen tension is an effective method to enhance the osteogenic ability of MSCs used for OMCSs.

Muscle Weakness in the Empty and Full Can Tests Cannot Differentiate Rotator Cuff Tear from Cervical Spondylotic Amyotrophy: Pain Provocation is a Useful Finding

Purpose: Rotator cuff tears and cervical spondylotic amyotrophy (CSA) are often confused as the main symptom in those with difficulty in shoulder elevation. Empty and full can tests are frequently used for the clinical diagnosis of rotator cuff tears. The aim of the present study was to investigate whether the empty and full can test results can help differentiate rotator cuff tears from CSA. Methods: Twenty-seven consecutive patients with rotator cuff tears and 25 with CSA were enrolled. We prospectively performed empty and full can tests in patients with rotator cuff tears and CSA. The following signs were considered positive: (a) muscle weakness during the empty can test, (b) muscle weakness during the full can test, (c) pain provocation during the empty can test, and (d) pain provocation during the full can test. We calculated the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of rotator cuff tears for each positive finding. Results: The sensitivity and specificity of each index were as follows (sensitivity, specificity, PPV, NPV): (a) 77.8%, 0%, 45.7%, 0%; (b) 66.7%, 4.0%, 42.9%, 10.0%; (c) 88.9%, 96.0%, 96.0%, 88.9%; and (d) 74.1%, 96.0%, 95.2%, 77.4%. There were significant differences for each index. Conclusion: Muscle weakness during the empty and full can tests was not useful in differentiating rotator cuff tears from CSA because of low specificity and PPV. However, pain provocation was useful in differentiating these two conditions because of high specificity and PPV.