Treatment of refractory non-union after maxillary osteotomy: A case report.

Maxillary non-union is a rare complication that occurs after an orthognathic surgery such as Le Fort I osteotomy. Here, we report a case of refractory non-union after maxillary osteotomy, which required a second surgery with bone graft. A 33-year-old man who had undergone bimaxillary osteotomy complained of an abnormal sensation in the right alar part about 1 year after the surgery. The patient was diagnosed as having maxillary non-union. Although surgical stabilization was performed using titanium plates, the non-union remained. The re-fusion surgery was performed about 3 years after the bimaxillary osteotomy with autologous bone graft using a biodegradable fixation system. At the 1-year follow up, the maxillary non-union was healed both clinically and radiographically. Re-fusion surgery using bone graft with biodegradable fixation might be an effective treatment option in cases of prolonged non-union that becomes evident after a long period following the initial maxillary osteotomy.

Development of thermal image plate using ceramic luminescence materials for aligning and stabilizing beam axis of CO2 laser.

A thermal image plate (TIP) using ceramic luminescence materials has been developed in order to visualize a beam spot of a CO2 laser which is used as a light source of an interferometer developed in JT-60SA. By using CaAlSiN3:Eu2+ (CASN), the TIP was developed, and its property was assessed. A CASN TIP was able to visualize the invisible CO2 laser beam as a negative image. The beam diameter and the stability of the beam axis measurement obtained with the CASN TIP were approximately the same as that obtained with a commercial TIP. Furthermore, the time response of the CASN TIP at the best was approximately the same as that of the commercial TIP. The CASN TIP which had the highest time response was applied to the beam axis stabilizer, and then the beam axis stabilization was successfully performed in 2 h.

PRR11 immunoreactivity is a weak prognostic factor in non-mucinous invasive adenocarcinoma of the lung.

INTRODUCTION: Proline-rich protein 11 (PRR11) functions in the progression of cell cycle, and silencing the PRR11 gene in lung cancer cells results in the inhibition of cellular proliferation, cell cycle progression, cell migration, invasion and colony formation. PRR11 may therefore be a therapeutic target in lung cancer. MATERIALS AND METHODS: Microarrays of surgical specimens of non-mucinous invasive adenocarcinoma of the lung, from 346 subjects that were not given preoperative therapy, were autoimmunostained with PRR11 and, except for trace and pseudo-positivity, assessed as "positive" at any proportion and intensity. RESULTS: PRR11 immunoreactivity demonstrated a tendency to associate with an aggressive phenotype (tumor size, vascular invasion, and adjuvant therapy) and some effect on overall survival (Hazard ratio 1.51). CONCLUSIONS: PRR11 may be a weak prognostic indicator of overall survival of patients with non-mucinous invasive adenocarcinoma of the lung.

ß-Cell-targeted blockage of PD1 and CTLA4 pathways prevents development of autoimmune diabetes and acute allogeneic islets rejection.

Protection of ß cells from autoimmune destruction potentially cures type 1 diabetes mellitus (T1D). During antigen presentation, interactions between cytotoxic T-lymphocyte antigen-4 (CTLA4) and B7 molecules, or programmed death 1 (PD1) and its ligand PDL1, negatively regulate immune responses in a non-redundant manner. Here we employed ß-cell-targeted adeno-associated virus serotype 8 (AAV8)-based vectors to overexpress an artificial PDL1-CTLA4Ig polyprotein or interleukin 10 (IL10). ß-Cell-targeted expression of PDL1-CTLA4Ig or IL10 preserved ß-cell mass and protected NOD mice from T1D development. When NOD mice were treated with vectors at early onset of hyperglycemia, PDL1-CTLA4Ig or IL10 alone failed to normalize the early onset of hyperglycemia. When drug-induced diabetic mice received major histocompatibility complex (MHC)-matched allo-islets, with or without pretreatment of the PDL1-CTLA4Ig-expressing vector, PDL1-CTLA4Ig-expressing islets were protected from rejection for at least 120 days. Similarly, transplantation of PDL1-CTLA4Ig-expressing MHC-matched islets into mice with established T1D resulted in protection of allo-islets from acute rejection, although islet grafts were eventually rejected. Thus the present study demonstrates the potent immuno-suppressive effects of ß-cell-targeted PDL1-CTLA4Ig overexpression against T1D development and allo-islet rejection. The gene-based simultaneous inhibition of PD1 and CTLA4 pathways provides a unique strategy for immunosuppression-free tissue/organ transplantation, especially in the setting of no established autoimmunity.

Transcriptional CCND1 expression as a predictor of poor response to neoadjuvant chemotherapy with trastuzumab in HER2-positive/ER-positive breast cancer.

Several trials have confirmed that the pathological complete response (pCR) rates after neoadjuvant chemotherapy (NAC) are significantly lower in HER2-positive/ER-positive patients than in HER2-positive/ER-negative patients. To understand this phenomenon, we investigated the association between NAC resistance and CCND1, which is frequently overexpressed in ER-positive tumors. Pretreatment formalin-fixed tumor tissues were collected from 75 HER2-positive patients receiving NAC comprised anthracyclines, taxanes, and trastuzumab. Seventeen gene transcripts along with PIK3CA mutations were detected using MassARRAY (Sequenom, San Diego, CA). The gene expression levels were dichotomized according to the median values. The immunohistochemical expression of ER, PTEN, BCL-2, and cyclin D1 was scored. The relationship between the variables was assessed using the Spearman correlation. A logistic regression analysis was performed to detect predictors of pCR, which was defined as no invasive tumor in the breast or axilla. Forty-seven percent of the cases were ER-positive and 52 % (40/63 % in ER-positive/ER-negative) achieved a pCR. Among the ER-positive patients, the CCND1 gene expression level was 2.1 times higher than that in ER-negative patients and was significantly correlated with the expression of cyclin D1 protein. In a univariate analysis, a pCR was associated with high mRNA levels of ESR1, PGR, LMTK3, HER2, IGF1R, INPP4B, PDL-1, BCL-2, and CCND1 (P ≤ 0.05). In contrast, none of these genes were significantly correlated with a pCR among the ER-negative tumors and only EGFR was significantly correlated with a pCR. PIK3CA mutations or PTEN loss were not associated with a pCR in either group. After excluding ESR1 (r = 0.58), PGR (r = 0.64), and IGF1R (r = 0.59), the expressions of which were correlated with CCND1, a multivariate analysis revealed that CCND1 [P = 0.043; OR, 0.16] and HER2 [P = 0.012; OR, 11.2] retained its predictive value for pCR among ER-positive patients, but not among ER-negative patients. A High Level of CCND1 gene expression is a poor predictor of a pCR and provides a rationale for evaluating CDK4/6 inhibitors in HER2-positive/ER-positive breast cancer patients.

A randomized phase III trial of postoperative adjuvant therapy for completely resected stage IA-IIIA lung cancer using an anti­angiogenetic agent: irsogladine maleate.

AIM: Although angiogenesis plays an important role in the invasion and metastasis of solid tumors, very few anti-angiogenetic drugs have been developed. Reexamining the anti-angiogenetic effects of existing drugs such as Thalidomide is another possible strategy for drug discovery. Irsogladine maleate (IM) is a drug invented to treat gastric ulcers; however, several reports have shown that IM also exerts anti-angiogenetic effects in vitro, in vivo and in humans. In order to elucidate whether treatment with IM would improve the prognoses of patients with resected lung cancer, we conducted a randomized trial. METHODS: In the control group, uracil-tegafur (250 mg/m2/day) was administered for two years to patients with resected stage IB - IIIA lung cancer, and no adjuvant therapy was administered to those with stage IA disease. In the study group, IM (4 mg/body/day) was additionally administered for two years. RESULTS: No significant differences were observed in the major prognostic factors among 305 eligible patients between the study and control groups. Adverse effects were minimal. The overall survival of the patients in the study and control groups were not statistically different. When the analysis was stratified by regimen, among the patients with resected stage IA disease, disease-specific survival in the study group was slightly higher than that in the control group; however, the difference was not significant (p=0.07). CONCLUSION: Although it could not be proven that IM improves the prognoses of resected lung cancer patients, IM might have some effect on resected stage IA disease, and another trial should be conducted.

Optical designs of reflection and refraction collection optics for a JT-60SA core Thomson scattering system.

Collection optics for core measurements in a JT-60SA Thomson scattering system were designed. The collection optics will be installed in a limited space and have a wide field of view and wide wavelength range. Two types of the optics are therefore suggested: refraction and reflection types. The reflection system, with a large primary mirror, avoids large chromatic aberrations. Because the size limit of the primary mirror and vignetting due to the secondary mirror affect the total collection throughput, conditions that provide the high throughput are found through an optimization. A refraction system with four lenses forming an Ernostar system is also employed. The use of high-refractive-index glass materials enhances the freedom of the lens curvatures, resulting in suppression of the spherical and coma aberration. Moreover, sufficient throughput can be achieved, even with smaller lenses than that of a previous design given in [H. Tojo, T. Hatae, T. Sakuma, T. Hamano, K. Itami, Y. Aida, S. Suitoh, and D. Fujie, Rev. Sci. Instrum. 81, 10D539 (2010)]. The optical resolutions of the reflection and refraction systems are both sufficient for understanding the spatial structures in plasma. In particular, the spot sizes at the image of the optics are evaluated as ~0.3 mm and ~0.4 mm, respectively. The throughput for the two systems, including the pupil size and transmissivity, are also compared. The results show that good measurement accuracy (<10%) even at high electron temperatures (<30 keV) can be expected in the refraction system.

Distinct outcome of stage I lung adenocarcinoma with ACTN4 cell motility gene amplification.

BACKGROUND: Even if detected at an early stage, a substantial number of lung cancers relapse after curative surgery. However, no method for distinguishing such tumors has yet been established. PATIENTS AND METHODS: The copy number of the actinin-4 (ACTN4) gene was determined by fluorescence in situ hybridization on tissue microarrays comprising 543 surgically resected adenocarcinomas of the lung. RESULTS: Amplification (an increase in the copy number by ≥ 2.0 fold) of the ACTN4 gene was detected in two of seven lung adenocarcinoma cell lines and 79 (15%) of 543 cases of pathological stage I-IV lung adenocarcinoma. Multivariate analysis revealed that ACTN4 gene amplification was the most significant independent factor associated with an extremely high risk of death (hazard ratio, 6.78; P = 9.48 × 10(-5), Cox regression analysis) among 290 patients with stage I lung adenocarcinoma. The prognostic significance of ACTN gene amplification was further validated in three independent cohorts totaling 1033 patients. CONCLUSIONS: Amplification of the ACTN4 gene defines a small but substantial subset of patients with stage I lung adenocarcinoma showing a distinct outcome. Such patients require intensive medical attention and might benefit from postoperative adjuvant chemotherapy.

Diagnostic and prognostic significance of the alternatively spliced ACTN4 variant in high-grade neuroendocrine pulmonary tumours.

BACKGROUND: High-grade neuroendocrine tumours (HGNTs) of the lung manifest a wide spectrum of clinical behaviour, but no method for predicting their outcome has been established. MATERIALS AND METHODS: We newly established a monoclonal antibody specifically recognizing the product of the alternatively spliced ACTN4 transcript (namely, variant actinin-4), and used it to examine the expression of variant actinin-4 immunohistochemically in a total of 609 surgical specimens of various histological subtypes of lung cancer. RESULTS: Variant actinin-4 was expressed in 55% (96/176) of HGNTs, but in only 0.8% (3/378) of non-neuroendocrine (NE) lung cancers. The expression of variant actinin-4 was significantly associated with poorer overall survival in HGNT patients (P=0.00021, log-rank test). Multivariate analysis using the Cox proportional hazards model showed that the expression of variant actinin-4 was the most significant independent negative predictor of survival in HGNT patients (hazard ratio (HR), 2.15; P=0.00113) after the presence of lymph node metastasis (HR, 2.25; P=0.00023). CONCLUSIONS: The expression of variant actinin-4 is an independent prognostic factor for patients with HGNTs. This protein has a high affinity for filamentous actin polymers and likely promotes aggressive behaviour of cancer cells. The present clinical findings clearly support this notion.

[Cryptorchidism associated with ectopic adrenal cortical tissue in the spermatic cord in a 51-year-old male]. / Un cas de cryptochidie associée à un îlot surrénalien ectopique du cordon spermatique chez un homme de 51ans.

This case report describes an exceptional case of ectopic adrenal cortex tissue (EACT) in the spermatic cord associated with ipsilateral cryptorchidism in an adult. While both EACT and cryptorchidism are fairly common congenital anomalies in boys, adult cases are uncommon. Although the spermatic cord is a known site of EACT, the reports of its association with cryptorchidism have been limited to child cases. During surgery, undescended testis was discovered and incidentally ectopic adrenal tissue along the spermatic cord was also identified. This combination of developmental aberrations in the adult has not been described, and the clinicopathological findings are reported with a brief literature review.

Rapid cytologic diagnosis of choroidal malignant melanoma by vitreous smear.

The eye is an uncommon subject of cytopathological examination. However, cytopathologic examination may be required for definitive diagnosis in some cases, as malignant tumors of the eye may sometimes be difficult to distinguish clinically from benign disorders. We report a case of malignant melanoma (MM) of the choroid, in which vitrectomy was performed for the initial clinical diagnosis of vitreous hemorrhage. As the dense vitreous hemorrhage was gradually cleared during the vitrectomy, a choroidal mass was discovered and the vitreous fluid was procured for rapid cytologic diagnosis. We used a modified Shorr's stain that can be completed within several minutes. With this method, highly atypical, pleomorphic cancer cells, occasionally associated with melanin pigment granules, were demonstrated. These cytologic findings indicated a diagnosis of MM arising from the choroid. Histologic examination of the enucleated eye confirmed MM of epithelioid type. The advantage and indication of the rapid cytologic diagnosis is discussed.

[Plasmacytoid urothelial carcinoma of the bladder with prostate cancer: report of two cases]. / Variante plasmacytoïde de carcinome urothélial vésical et cancer prostatique : à propos de deux cas.

Plasmacytoid urothelial carcinoma (PUC) is a rare variant of urothelial carcinoma with aggressive clinicopathological behaviours. We experienced two cases of PUC of urinary bladder. Both cases were advanced cancer with extravesical invasion and lymph node metastases. They also had coexisting prostatic carcinoma, one was preoperatively diagnosed and the other was incidentally discovered after surgery. As these cases were the first report of PUC simultaneously associated with prostatic carcinoma, clinicopathological features and the treatment options were discussed.

Systemic non-amyloidotic fibril deposition disease: a probable variant form of fibrillary glomerulonephritis.

Fibrillary glomerulonephritis (FGN) is characterized by deposition of non-amyloidotic fibrillary material in glomeruli, and most patients with the disease show heavy proteinuria and hematuria, and progress into end-stage renal failure. We report a 62-year-old woman with FGN who showed mild proteinuria without hematuria and developed rapidly progressive renal failure requiring hemodialysis. Renal biopsy showed severe tubulointerstitial injury associated with non-amyloidotic fibrillary deposits in the tubular basement membrane, interstitium and vessel walls, in addition to glomeruli. The patient died from liver abscess 1 year after the introduction of hemodialysis. Postmortem examination showed the presence of non-amyloidotic fibrillary deposits arranged in tightly packed electron-dense and bundle-shaped structures in many organs. These findings suggest systemic non-amyloidotic fibril deposition in FGN.

Indolactam V/GLP-1-mediated differentiation of human iPS cells into glucose-responsive insulin-secreting progeny.

Nuclear reprogramming of somatic tissue enables derivation of induced pluripotent stem (iPS) cells from an autologous, non-embryonic origin. The purpose of this study was to establish efficient protocols for lineage specification of human iPS cells into functional glucose-responsive, insulin-producing progeny. We generated human iPS cells, which were then guided with recombinant growth factors that mimic the essential signaling for pancreatic development. Reprogrammed with four stemness factors, human fibroblasts were here converted into authentic iPS cells. Under feeder-free conditions, fate specification was initiated with activin A and Wnt3a that triggered engagement into definitive endoderm, followed by priming with fibroblast growth factor 10 (FGF10) and KAAD-cyclopamine. Addition of retinoic acid, boosted by the pancreatic endoderm inducer indolactam V (ILV), yielded pancreatic progenitors expressing pancreatic and duodenal homeobox 1 (PDX1), neurogenin 3 (NGN3) and neurogenic differentiation 1 (NEUROD1) markers. Further guidance, under insulin-like growth factor 1 (IGF-1), hepatocyte growth factor (HGF) and N-[N-(3,5-Difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester (DAPT), was enhanced by glucagon-like peptide-1 (GLP-1) to generate islet-like cells that expressed pancreas-specific markers including insulin and glucagon. Derived progeny demonstrated sustained expression of PDX1, and functional responsiveness to glucose challenge secreting up to 230 pM of C-peptide. A pancreatogenic cocktail enriched with ILV/GLP-1 offers a proficient means to specify human iPS cells into glucose-responsive hormone-producing progeny, refining the development of a personalized platform for islet-like cell generation.

Design of collection optics and polychromators for a JT-60SA Thomson scattering system.

This paper presents designs of collection optics for a JT-60SA Thomson scattering system. By using tangential (to the toroidal direction) YAG laser injection, three collection optics without strong chromatic aberration generated by the wide viewing angle and small design volume were found to measure almost all the radial space. For edge plasma measurements, the authors optimized the channel number and wavelength ranges of band-pass filters in a polychromator to reduce the relative error in T(e) by considering all spatial channels and a double-pass laser system with different geometric parameters.

Classic polyarteritis nodosa presenting with rapidly progressive renal insufficiency.

Rapidly progressive renal insufficiency is rare in patients with classic polyarteritis nodosa (cPAN). We describe two cases of cPAN who presented with rapid and progressive deterioration of renal function. Renal biopsies showed severe necrotizing vasculitis in medium-sized arteries but no changes in glomeruli. Combination therapy of corticosteroid and cyclophosphamide resulted in marked improvement of clinical symptoms, amelioration of renal function and lack of subsequent relapse of vasculitis. These findings suggest good prognosis of patients with cPAN who show rapid and progressive deterioration of renal function who respond to immunosuppressive therapy.

Relationship between ease of swallowing and deglutition-related muscle activity in various postures.

The purpose of this study was to investigate the relationship between the ease of swallowing and the deglutition-related muscle activity in various body and head postures by surface electromyography (EMG). Bipolar surface electrodes were placed on the right suprahyoid and infrahyoid muscles of nine healthy adults (19-28 years) while swallowing jelly. Ten postures per subject were examined: five body angulations (0 degrees [supine], 30 degrees, 60 degrees, 90 degrees [upright] and 120 degrees from the horizontal) and two head positions (chin-up and chin-down). The duration and amplitude of suprahyoid and infrahyoid muscle activity were measured by an electromyograph, and the ease of swallowing was subjectively determined by using a rating scale (0 = difficult to swallow, 10 = easy to swallow). The group-average duration and amplitude of muscle activity and the group-average rating scales mostly showed insignificant changes with the body angulations independent of the head positions. Interestingly, the duration and amplitude of muscle activity during swallowing were negatively correlated with the rating scales, indicating that a shorter duration and smaller activity of muscle activity corresponds to easier swallowing. Consequently, the duration and amplitude of suprahyoid and infrahyoid muscle activity measured by surface EMG would be a useful indicator of the easy-to-swallow performance.