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Study Design: A single-center retrospective study. Purpose: To investigate the prevalence of proximal junctional kyphosis (PJK) and its risk factors after surgical treatment of adult spinal deformity (ASD) with oblique lateral interbody fusion (OLIF). Overview of Literature: Correction of ASD using OLIF has been developed because it is less invasive, and enables correction of severe deformities. Although PJK is a well-recognized complication after the correction of spinal deformity, few studies have evaluated the prevalence and risk factors for PJK after OLIF for ASD. Methods: We reviewed 74 patients who underwent surgery for ASD. PJK was defined as a proximal junction sagittal Cobb angle exceeding 10 degrees, and at least 10 degrees greater than the preoperative measurement. We investigated the following as risk factors: age, sex, body mass index, medical history, number of fused segments, number of interbody fusions, number of OLIFs, number of osteotomies, level of upper instrumented vertebrae, lowest instrumented vertebrae, and radiographic parameters. Results: The mean follow-up duration was 22.4 months and the mean age of the patients was 73.6 years. PJK was present in 19/74 patients (25.7%) and absent in 55/74 (74.3%). In the univariate analysis, those with PJK had a significantly higher proportion of patients with a history of vertebral compression fracture (7/19 patients [36.8%] vs. 6/55 patients [10.9%], p=0.027). Those with PJK had a significantly higher proportion of patients with fusion to the pelvis (18/19 patients [94.7%] vs. 34/55 patients [61.8%], p=0.016). According to the multivariate analysis, fusion to the pelvis was a significant risk factor for PJK. Conclusions: Fusion to the pelvis was the most important risk factor for PJK. A history of vertebral compression fracture served as an additional risk factor for PJK. Clinicians should consider these factors before treating ASD patients with OLIF.

Systemic injection of a nerve growth factor (NGF) antibody has been proven to have a significant relevance in relieving osteoarthritis (OA) pain, while its adverse effects remain a safety concern for patients. A local low-dose injection is thought to minimize adverse effects. In this study, OA was induced in an 8-week-old male Sprague-Dawley (SD) rat joint by monoiodoacetate (MIA) injection for 2 weeks, and the effect of weekly injections of low-dose (1, 10, and 100 mu g) NGF antibody or saline (control) was evaluated. Behavioral tests were performed, and at the end of week 6, all rats were sacrificed and their knee joints were collected for macroscopic and histological evaluations. Results showed that 100 mu g NGF antibody injection relieved pain in OA rats, as evidenced from improved weight-bearing performance but not allodynia. In contrast, no significant differences were observed in macroscopic and histological scores between rats from different groups, demonstrating that intra-articular treatment does not worsen OA progression. These results suggest that local administration yielded a low effective NGF antibody dose that may serve as an alternative approach to systemic injection for the treatment of patients with OA.

Study Design: Single-center retrospective study. Purpose: To compare the physical function and quality of life (QOL) parameters of two minimally invasive surgical (MIS) procedures: oblique lateral interbody fusion with percutaneous posterior fixation in lateral position (OLIF-LPF) and minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) for single-level degenerative spondylolisthesis (DS). Overview of Literature: To date, many options for the surgical treatment of lumbar DS and reports have described the effectiveness of minimally invasive lateral access surgery and MIS-TLIF. However, there is still a paucity of comparative data regarding the physical function and QOL outcomes of OLIF and MIS-TLIF. Methods: Eighty-six patients were enrolled in this study (group O: OLIF-LPF, n=38; group T: MIS-TLIF, n=48). We evaluated the operation time, estimated blood loss (EBL), postoperative laboratory data, preoperative and postoperative radiographic parameters, overall functional outcome with the Japanese Orthopedic Association Back Pain Evaluation Questionnaire (JOABPEQ) effectiveness rate, and Visual Analog Scale (VAS) score for low back pain, leg pain, and leg numbness. Results: No statistical differences in operation time, EBL, and C-reactive protein level, 5 days postoperatively, between groups O and T. With respect to radiological outcome, preoperative and postoperative disc height change was significantly greater in group O than in group T (3.8 vs. 1.8 mm, p<0.05). Both groups showed postoperative improvements in the clinical outcome scores of all JOABPEQ domains, but the effectiveness rate increase in the psychological domain was significantly higher in group O than in group T (47.1% vs. 14.6%, p<0.05). No differences in the preoperative and postoperative VAS score change were noted between the two groups in any of the items. Conclusions: The changes in physical function and QOL parameters after OLIF-LPF and MIS-TLIF were almost equivalent; howeve

The aim of this study was to evaluate the joint contact area of the dominant side and that of the non-dominant side without valgus instability in symptomatic pitchers. Ten symptomatic elbow medial ulnar collateral ligament (UCL) deficient baseball pitchers participated in this study. Computed tomography (CT) data from the dominant and non-dominant elbows were obtained with and without elbow valgus stress. The CT imaging data of each elbow joint were reconstructed using a 3D reconstruction software package, and the radiocapitellar and ulnohumeral joint contact areas were calculated. The center of the contact area and the translation from the position without stress to the position with valgus stress were also calculated. With elbow valgus stress, the contact area changed, and the center of the radiocapitellar joint contact area translated significantly more laterally in the dominant elbow than in the non-dominant elbow (p = 0.0361). In addition, the center of the ulnohumeral joint contact area translated significantly more posteriorly in the dominant elbow than in the non-dominant elbow (p = 0.0413). These changes in contact areas could be the reason for cartilage injury at the posterior trochlea in pitchers with UCL deficiency.

Accumulating evidence suggests that synovitis is associated with osteoarthritic process. Macrophages play principal role in development of synovitis. Our earlier study suggests that interaction between cartilage fragments and macrophages exacerbates osteoarthritic process. However, molecular mechanisms by which cartilage fragments trigger cellular responses remain to be investigated. Therefore, the current study aims at analyzing molecular response of macrophages to cartilage fragments. To this end, we analyzed the transcriptional profiling of murine macrophages exposed to cartilage fragments by RNA sequencing. A total 153 genes were differentially upregulated, and 105 genes were down-regulated in response to cartilage fragments. Bioinformatic analysis revealed that the most significantly enriched terms of the upregulated genes included scavenger receptor activity, integrin binding activity, TNF signaling, and toll-like receptor signaling. To further confirm our results, immunohistochemical staining was performed to detected regulated molecules in synovial tissues of OA patients. In consistence with RNA-seq results, MARCO, TLR2 and ITG alpha 5 were mainly detected in the intima lining layer of synovial tissues. Moreover, blockade of TLR2 or ITG alpha 5 but not Marco using specific antibody significantly reduced production of TNF-alpha in stimulated macrophages by cartilage fragments. Our data suggested that blocking TLR2 or ITG alpha 5 might be promising therapeutic strategy for treating progressive osteoarthritis.

type:Journal Article, Objective: We developed and demonstrated laser speckle flowgraphy (LSFG) for two-dimensional (2D) skin blood flow (SBF) measurements to facilitate the noninvasive comparisons of SBF between individuals. Approach: By using morphing technology with a face mesh to compare SBF spatial distributions among individuals, we examined the practicability of SBF measurement with LSFG. Main results: (1) The uniformity of SBF measurement was demonstrated by examinations at different distances and angles for healthy subjects. (2) Mean blur rate (MBR)—a blood flow index of LSFG—exhibited significant correlation with the thermal diffusion method (TDM)—an established blood flow measurement method—suggesting that MBR is an effective index of SBF. (3) Blowout time, the half-width duration/duration of one cardiac cycle, exhibited significant negative correlation with age and positive correlation with stratum corneum hydration. Significance: These results suggest that LSFG is useful for evaluating SBF-related skin properties, and it has significant potential in medicine and cosmetology.

As articular cartilages have rarely healed by themselves because of their characteristics of avascularity and low cell density, surgical intervention is ideal for patients with cartilaginous injuries. Because of structural characteristics of the cartilage tissue, a three-dimensional culture of stem cells in biomaterials is a favorable system on cartilage tissue engineering. Induced pluripotent stem cells (iPSCs) are a new cell source in cartilage tissue engineering for its characteristics of self-renewal capability and pluripotency. However, the optimal cultivation condition for chondrogenesis of iPSCs is still unknown. Here we show that a novel chondrogenic differentiation method of iPSCs using the combination of three-dimensional cultivation in ultra-purified alginate gel (UPAL gel) and multi-step differentiation via mesenchymal stem cell-like cells (iPS-MSCs) could efficiently and specifically differentiate iPSCs into chondrocytes. The iPS-MSCs in UPAL gel culture sequentially enhanced the expression of chondrogenic marker without the upregulation of that of osteogenic and adipogenic marker and histologically showed homogeneous chondrogenic extracellular matrix formation. Our results suggest that the pluripotency of iPSCs can be controlled when iPSCs are differentiated into iPS-MSCs before embedding in UPAL gel. These results lead to the establishment of an efficient three-dimensional system to engineer artificial cartilage tissue from iPSCs for cartilage regeneration. (c) 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 1086-1093, 2019.

BackgroundA vitamin A derivative, 13-cis-retinoic acid (isotretinoin), has been administered to treat several types of pediatric cancer and has improved survival rates in patients despite being known to induce premature epiphyseal closure. As the number of patients treated by 13-cis-retinoic acid increases, demands for salvage treatment after systemic retinoid therapy are emerging. However, few studies have described the surgical treatment of this disease.Case presentationWe report a case with bilateral varus knee deformity due to premature epiphyseal closure that occurred during treatment with isotretinoin for neuroblastoma. The patient was successfully treated with correction osteotomy using a Taylor spatial frame in the right knee joint and femoral closed wedge osteotomy using a locking plate in left knee joint. Histopathological examination of the growth plate showed polar irregularity of chondrocytes and decreased cartilage matrix without apoptosis. In contrast, arthroscopic findings showed an intact joint surface. No recurrence of varus deformity was evident on follow-up at 1year.ConclusionsTo the best of our knowledge, this represents the first report of correction osteotomy for varus knee deformity due to premature epiphyseal closure that occurred during treatment with isotretinoin.

BackgroundA vitamin A derivative, 13-cis-retinoic acid (isotretinoin), has been administered to treat several types of pediatric cancer and has improved survival rates in patients despite being known to induce premature epiphyseal closure. As the number of patients treated by 13-cis-retinoic acid increases, demands for salvage treatment after systemic retinoid therapy are emerging. However, few studies have described the surgical treatment of this disease.Case presentationWe report a case with bilateral varus knee deformity due to premature epiphyseal closure that occurred during treatment with isotretinoin for neuroblastoma. The patient was successfully treated with correction osteotomy using a Taylor spatial frame in the right knee joint and femoral closed wedge osteotomy using a locking plate in left knee joint. Histopathological examination of the growth plate showed polar irregularity of chondrocytes and decreased cartilage matrix without apoptosis. In contrast, arthroscopic findings showed an intact joint surface. No recurrence of varus deformity was evident on follow-up at 1year.ConclusionsTo the best of our knowledge, this represents the first report of correction osteotomy for varus knee deformity due to premature epiphyseal closure that occurred during treatment with isotretinoin.

As articular cartilages have rarely healed by themselves because of their characteristics of avascularity and low cell density, surgical intervention is ideal for patients with cartilaginous injuries. Because of structural characteristics of the cartilage tissue, a three-dimensional culture of stem cells in biomaterials is a favorable system on cartilage tissue engineering. Induced pluripotent stem cells (iPSCs) are a new cell source in cartilage tissue engineering for its characteristics of self-renewal capability and pluripotency. However, the optimal cultivation condition for chondrogenesis of iPSCs is still unknown. Here we show that a novel chondrogenic differentiation method of iPSCs using the combination of three-dimensional cultivation in ultra-purified alginate gel (UPAL gel) and multi-step differentiation via mesenchymal stem cell-like cells (iPS-MSCs) could efficiently and specifically differentiate iPSCs into chondrocytes. The iPS-MSCs in UPAL gel culture sequentially enhanced the expression of chondrogenic marker without the upregulation of that of osteogenic and adipogenic marker and histologically showed homogeneous chondrogenic extracellular matrix formation. Our results suggest that the pluripotency of iPSCs can be controlled when iPSCs are differentiated into iPS-MSCs before embedding in UPAL gel. These results lead to the establishment of an efficient three-dimensional system to engineer artificial cartilage tissue from iPSCs for cartilage regeneration. (c) 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 1086-1093, 2019.

BackgroundGood outcomes have been reported in revision total hip replacement with massive segmental defects using impaction bone grafting with circumferential metal meshes. However, the morphology of defects that require a mesh is poorly defined. The purpose of this study was to evaluate the effects of a variety of segmental defects on load transmission to the proximal femur under both axial and rotational loads.MethodsInitial stability of the Exeter stem was investigated in a composite bone model using three medial bone defect morphologies: Long (length 5cmxwidth 2cm), Short (2.5cmx2cm), Square (3.2cmx3.2cm), Square with mesh (3.2cmx3.2cm defect covered with metal mesh), and with no defect as control. Specimens (5 per group) were axially loaded and internally rotated up to 20 degrees or to failure. Strain distributions of the femora were measured using a strain gauge.ResultsAll Square group specimens failed while rotation was increasing. In the other four groups, failure was not observed in any specimens. Mean torsional stiffness in the Long (4.40.3Nm/deg.) and Square groups (4.3 +/- 0.3Nm/deg.) was significantly smaller than in the Control group (4.8 +/- 0.3Nm/deg.). In the medio-cranial region, the magnitude of the maximum principal strain in the Square group (1176.4 +/- 100.9) was significantly the largest (Control, 373.2 +/- 129.5, p<0.001; Long, 883.7 +/- 153.3, p=0.027; Short, 434.5 +/- 196.8, p<0.001; Square with mesh, 256.9 +/- 100.8, p<0.001). Torsional stiffness, and both maximum and minimum principal strains in the Short group showed no difference compared to the Control group in any region.Conclusions Bone defect morphology greatly affected initial stem stability and load transmission. If defect morphology is not wide and the distal end is above the lower end of the lesser trochanter, it may be acceptable to fill the bone defect region with bone cement. However, this procedure is not acceptable for defects extending distally below the lower end

Radiotherapy is used extensively in cancer treatment, but radioresistance and the metastatic potential of cancer cells that survive radiation remain critical issues. There is a need for novel treatments to improve radiotherapy. Here, we evaluated the therapeutic benefit of lambda-carrageenan (CGN) to enhance the efficacy of radiation treatment and investigated the underlying molecular mechanism. CGN treatment decreased viability in irradiated cancer cells and enhanced reactive oxygen species accumulation, apoptosis, and polyploid formation. Additionally, CGN suppressed radiation-induced chemoinvasion and invasive growth in 3D 1rECM culture. We also screened target molecules using a gene expression microarray analysis and focused on Rac GTPase-activating protein 1 (RacGAP1). Protein expression of RacGAP1 was upregulated in several cancer cell lines after radiation, which was significantly suppressed by CGN treatment. Knockdown of RacGAP1 decreased cell viability and invasiveness after radiation. Overexpression of RacGAP1 partially rescued CGN cytotoxicity. In a mouse xenograft model, local irradiation followed by CGN treatment significantly decreased tumor growth and lung metastasis compared to either treatment alone. Taken together, these results suggest that CGN may enhance the effectiveness of radiation in cancer therapy by decreasing cancer cell viability and suppressing both radiation-induced invasive activity and distal metastasis through downregulating RacGAP1 expression.

BackgroundGood outcomes have been reported in revision total hip replacement with massive segmental defects using impaction bone grafting with circumferential metal meshes. However, the morphology of defects that require a mesh is poorly defined. The purpose of this study was to evaluate the effects of a variety of segmental defects on load transmission to the proximal femur under both axial and rotational loads.MethodsInitial stability of the Exeter stem was investigated in a composite bone model using three medial bone defect morphologies: Long (length 5cmxwidth 2cm), Short (2.5cmx2cm), Square (3.2cmx3.2cm), Square with mesh (3.2cmx3.2cm defect covered with metal mesh), and with no defect as control. Specimens (5 per group) were axially loaded and internally rotated up to 20 degrees or to failure. Strain distributions of the femora were measured using a strain gauge.ResultsAll Square group specimens failed while rotation was increasing. In the other four groups, failure was not observed in any specimens. Mean torsional stiffness in the Long (4.40.3Nm/deg.) and Square groups (4.3 +/- 0.3Nm/deg.) was significantly smaller than in the Control group (4.8 +/- 0.3Nm/deg.). In the medio-cranial region, the magnitude of the maximum principal strain in the Square group (1176.4 +/- 100.9) was significantly the largest (Control, 373.2 +/- 129.5, p<0.001; Long, 883.7 +/- 153.3, p=0.027; Short, 434.5 +/- 196.8, p<0.001; Square with mesh, 256.9 +/- 100.8, p<0.001). Torsional stiffness, and both maximum and minimum principal strains in the Short group showed no difference compared to the Control group in any region.Conclusions Bone defect morphology greatly affected initial stem stability and load transmission. If defect morphology is not wide and the distal end is above the lower end of the lesser trochanter, it may be acceptable to fill the bone defect region with bone cement. However, this procedure is not acceptable for defects extending distally below the lower end of the l

BACKGROUND: To investigate the possible role of fluid mechanical factors in thromboembolism that occurs at a high rate in the human middle cerebral artery (MCA). METHODS: Isolated transparent cerebral arterial trees containing the terminal bifurcation of the internal carotid artery (ICA), where the ICA bifurcated into the MCA and the anterior cerebral artery, were prepared from human cadavers. The flow behavior and distribution of embolus-model polystyrene particles in dilute suspensions at the bifurcation were studied in detail by means of flow visualization and high-speed cinemicrographic techniques. RESULTS: Large particles in suspensions flowing through the ICA migrated radially away from the vessel wall toward the axis of the ICA. It became more remarkable by increasing the flow rate in the ICA (Q(0)), flow rate ratio of Q(1) to Q(0) (MCA/ICA), and particle diameter. As a result, redistribution of particles flowing in the ICA occurred at the bifurcation. The particles >1 mm in diameter (approximate to 1/4 of vessel diameter) selectively entered the MCA, even when the flow rate ratio of Q(1) to Q(0) was decreased to as low as 0.34. In contrast, the particles whose diameters were <0.3 mm (approximate to 1/10 of vessel diameter) and that did not show radial migration entered the MCA at the same rate as the flow rate ratio of Q(1) to Q(0). CONCLUSIONS: Due to the flow-dependent migration of particles away from the vessel wall toward the axis of the ICA, large particles selectively enter the MCA to which the core flow of the ICA is generally directed. This might explain why the incidence of thromboembolism is higher in the MCA than in the anterior cerebral artery in humans.

Background: To investigate the prognostic value of oligo-recurrence in patients with brain-only oligometastases of non-small cell lung cancer (NSCLC) treated with stereotactic radiosurgery (SRS) or stereotactic radiotherapy (SRT). Methods: Patients treated with SRS or SRT for brain-only NSCLC oligometastases in 6 high-volume institutions in Japan between 1996 and 2008 were reviewed. Eligible patients met 1), 2), and 4) or 1), 3), and 4) of the following: 1) NSCLC with 1 to 4 brain metastases on magnetic resonance imaging (MRI) treated with SRS or SRT; 2) control of the primary lesions (thorax) at the time of SRS or SRT for brain metastases (patients meeting this criterion formed the oligo-recurrence group); 3) with SRS or SRT for brain metastases, concomitant treatment for active primary lesions (thorax) with curative surgery or curative stereotactic body radiotherapy (SBRT), or curative chemoradiotherapy (sync-oligometastases group); and 4) Karnofsky performance status (KPS) ≥70. Results: The median overall survival (OS) of all 61 patients was 26 months (95 % CI: 17.5–34.5 months). The 2-year and 5-year overall survival rates were 60.7 and 15.7 %, respectively. Stratified by oligostatus, the sync-oligometastases group achieved a median OS of 18 months (95 % CI: 14.8–21.1 months) and a 5-year OS of 0 %, while the oligo-recurrence group achieved a median OS of 41 months (95 % CI: 27.8–54.2 months) and a 5-year OS of 18.6 %. On multivariate analysis, oligo-recurrence was the only significant independent factor related to a favorable prognosis (hazard ratio: 0.253 (95 % CI: 0.082–0.043) (p = 0.025). Conclusions: The presence of oligo-recurrence can predict a favorable prognosis of brain-only oligometastases in patients with NSCLC treated with SRS or SRT.

Recent progress in the treatment for pediatric malignancies using a combination of surgery, chemotherapy, and radiotherapy has improved survival. However, late toxicities of radiotherapy are a concern in long‐term survivors. A recent study suggested reduced secondary cancer and other late toxicities after proton beam therapy (PBT) due to dosimetric advantages. In this study, we evaluated the safety and efficacy of PBT for pediatric patients treated in Japan. A retrospective observational study in pediatric patients who received PBT was performed. All patients aged <20 years old who underwent PBT from January 1983 to August 2014 at four sites in Japan were enrolled in the study. There were 343 patients in the study. The median follow‐up periods were 22.6 months (0.4–374.3 months) for all patients and 30.6 months (0.6–374.3 months) for survivors. The estimated 1‐, 3‐, 5‐, and 10‐year survival rates were 82.7% (95% CI: 78.5–87.0%), 67.4% (61.7–73.2%), 61.4% (54.8–67.9%), and 58.7% (51.5–65.9%), respectively. Fifty‐two events of toxicity ≥ grade 2 occurred in 43 patients. Grade 4 toxicities of myelitis, visual loss (two cases), cerebral vascular disease, and tissue necrosis occurred in five patients. This study provides preliminary results for PBT in pediatric patients in Japan. More experience and follow‐up with this technique are required to establish the efficacy of PBT in this patient population.

type:Text, During the 1990s, laparoscopic resection was established as a treatment for gastrointestinal malignant tumors. A number of randomized controlled trials comparing laparoscopic-assisted colorectal surgery with conventional open colorectal surgery for colon cancer have been conducted. These trials have shown short-term benefits, and the vast majority demonstrated no significant difference in long-term outcomes. Laparoscopic-assisted colorectal surgery is widely performed for the treatment of colon cancer, whereas laparoscopic-assisted colorectal surgery for rectal cancer is less commonly performed. In recent years, there have been an increasing number of reports of laparoscopic-assisted colorectal surgery for rectal cancer, where improving short-term outcomes was shown, but no definitive effect on long-term survival has been shown to date. Randomized controlled trials focusing on long-term survival are currently ongoing.

Background: Surgical radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC) is associated with superior oncological outcome in comparison with percutaneous RFA. The present study aimed to retrospectively evaluate the relative perioperative safety and postoperative outcome of the laparoscopic or thoracoscopic approach versus the open approach to RFA for small HCC., Methods: A retrospective analysis was performed in 55 consecutive patients who underwent open (n = 32) or laparoscopic/thoracoscopic (LTS) RFA (n = 23) for primary unresectable HCC between January 2005 and December 2010. Baseline characteristics, survival/recurrence rates, and complications after treatment were compared between the two groups., Results: There was a trend showing that LTS RFA was performed for tumors located in the anterior segment (e.g., segments III, V, VIII). The LTS RFA group had a significantly lower intraoperative blood loss, shorter operative time, and shorter postoperative hospital stay, compared with the open RFA group. No major postoperative complications occurred in patients who underwent LTS RFA. No significant differences in overall survival, recurrence-free survival and local recurrence rates were observed between the two groups., Conclusions: In consideration of operative invasiveness and postoperative recovery, LTS RFA is superior to the open approach in patients with small HCC. Moreover, the surgical outcome did not differ between the two approaches. Laparoscopic/thorascopic RFA can be considered to be a useful procedure for ablation therapy.

MicroRNAs (miRNAs), a class of small noncoding RNAs, regulate protein-coding gene expression by repressing translation or cleaving RNA transcripts in a sequence-specific manner. A growing body of evidence suggests that miRNAs contribute to bladder cancer development, progression and metastasis. Genome-wide miRNA expression signatures have been used to rapidly and precisely identify aberrant miRNA expression in bladder cancer. Based on reports describing miRNA signatures, several downregulated and upregulated miRNAs have been discovered. Examination of the differential expression of miRNAs between clinical bladder cancer and normal bladder tissue has led to the elucidation of 11 miRNA expression signatures. miRNAs downregulated in bladder cancer, such as miR-145, miR-143 and miR125b, are known to be tumour suppressors, whereas upregulated miRNAs, such as miR-183, miR-96, miR17-5p and miR-20a are oncogenic. Several studies have demonstrated the potential of miRNAs for providing prognostic information. miR-145 is the most frequently downregulated miRNA in bladder cancer and has been shown to significantly inhibit proliferation, migration and invasion. Understanding the role of differentially expressed miRNAs, as well as their molecular targets, in bladder cancer will provide an effective and promising strategy for miRNA-based therapeutics for the treatment of bladder cancer.

Background: To investigate the prognostic value of oligo-recurrence in patients with brain-only oligometastases of non-small cell lung cancer (NSCLC) treated with stereotactic radiosurgery (SRS) or stereotactic radiotherapy (SRT). Methods: Patients treated with SRS or SRT for brain-only NSCLC oligometastases in 6 high-volume institutions in Japan between 1996 and 2008 were reviewed. Eligible patients met 1), 2), and 4) or 1), 3), and 4) of the following: 1) NSCLC with 1 to 4 brain metastases on magnetic resonance imaging (MRI) treated with SRS or SRT; 2) control of the primary lesions (thorax) at the time of SRS or SRT for brain metastases (patients meeting this criterion formed the oligo-recurrence group); 3) with SRS or SRT for brain metastases, concomitant treatment for active primary lesions (thorax) with curative surgery or curative stereotactic body radiotherapy (SBRT), or curative chemoradiotherapy (sync-oligometastases group); and 4) Karnofsky performance status (KPS) ≥70. Results: The median overall survival (OS) of all 61 patients was 26 months (95 % CI: 17.5–34.5 months). The 2-year and 5-year overall survival rates were 60.7 and 15.7 %, respectively. Stratified by oligostatus, the sync-oligometastases group achieved a median OS of 18 months (95 % CI: 14.8–21.1 months) and a 5-year OS of 0 %, while the oligo-recurrence group achieved a median OS of 41 months (95 % CI: 27.8–54.2 months) and a 5-year OS of 18.6 %. On multivariate analysis, oligo-recurrence was the only significant independent factor related to a favorable prognosis (hazard ratio: 0.253 (95 % CI: 0.082–0.043) (p = 0.025). Conclusions: The presence of oligo-recurrence can predict a favorable prognosis of brain-only oligometastases in patients with NSCLC treated with SRS or SRT.

Recent progress in the treatment for pediatric malignancies using a combination of surgery, chemotherapy, and radiotherapy has improved survival. However, late toxicities of radiotherapy are a concern in long‐term survivors. A recent study suggested reduced secondary cancer and other late toxicities after proton beam therapy (PBT) due to dosimetric advantages. In this study, we evaluated the safety and efficacy of PBT for pediatric patients treated in Japan. A retrospective observational study in pediatric patients who received PBT was performed. All patients aged <20 years old who underwent PBT from January 1983 to August 2014 at four sites in Japan were enrolled in the study. There were 343 patients in the study. The median follow‐up periods were 22.6 months (0.4–374.3 months) for all patients and 30.6 months (0.6–374.3 months) for survivors. The estimated 1‐, 3‐, 5‐, and 10‐year survival rates were 82.7% (95% CI: 78.5–87.0%), 67.4% (61.7–73.2%), 61.4% (54.8–67.9%), and 58.7% (51.5–65.9%), respectively. Fifty‐two events of toxicity ≥ grade 2 occurred in 43 patients. Grade 4 toxicities of myelitis, visual loss (two cases), cerebral vascular disease, and tissue necrosis occurred in five patients. This study provides preliminary results for PBT in pediatric patients in Japan. More experience and follow‐up with this technique are required to establish the efficacy of PBT in this patient population.

Purpose: We determined prognostic factors associated with prolonged survival after metastasectomy for urothelial carcinoma. Materials and Methods: A total of 42 patients who underwent resection of urothelial carcinoma metastases with curative intent at 4 Japanese university hospitals were included in analysis. Of the patients 41 of 42 underwent systemic chemotherapy before and/or after metastasectomy. Overall survival was analyzed using the Kaplan-Meier method. The relationship between clinical characteristics and survival was analyzed using the log rank test. Results: Metastasectomy included lymph node dissection in 20 cases, pulmonary resection in 12, pelvic exenteration in 3, resection of local recurrence in 2, resection of subcutaneous metastasis in 2, liver resection in 1 and other in 2. Median overall survival was 29 months (IQR 19-80) from the initiation of treatment for metastases and 26 months (IQR 11-90) from metastasectomy. The overall 5-year survival rate after metastasectomy was 31%. On univariate analysis patients treated with metastasectomy for a solitary lung or solitary lymph node metastasis had significantly longer survival than the others who underwent metastasectomy (81 vs 19 months, log rank test p = 0.0296). Conclusions: Long-term cancer control could be achieved in a subgroup of patients who undergo metastasectomy, especially those with a solitary lung or solitary lymph node metastasis.

Purpose: We determined prognostic factors associated with prolonged survival after metastasectomy for urothelial carcinoma. Materials and Methods: A total of 42 patients who underwent resection of urothelial carcinoma metastases with curative intent at 4 Japanese university hospitals were included in analysis. Of the patients 41 of 42 underwent systemic chemotherapy before and/or after metastasectomy. Overall survival was analyzed using the Kaplan-Meier method. The relationship between clinical characteristics and survival was analyzed using the log rank test. Results: Metastasectomy included lymph node dissection in 20 cases, pulmonary resection in 12, pelvic exenteration in 3, resection of local recurrence in 2, resection of subcutaneous metastasis in 2, liver resection in 1 and other in 2. Median overall survival was 29 months (IQR 19-80) from the initiation of treatment for metastases and 26 months (IQR 11-90) from metastasectomy. The overall 5-year survival rate after metastasectomy was 31%. On univariate analysis patients treated with metastasectomy for a solitary lung or solitary lymph node metastasis had significantly longer survival than the others who underwent metastasectomy (81 vs 19 months, log rank test p = 0.0296). Conclusions: Long-term cancer control could be achieved in a subgroup of patients who undergo metastasectomy, especially those with a solitary lung or solitary lymph node metastasis.

Background: The clinical results of surgical procedures for severe Sprengel's deformity have been uncertain. To obtain improved elevation, we consider that it is necessary to realign the lateral border of the scapula for upward rotation. The purposes of the current study were to evaluate the clinical results and range of motion of the scapula after such realignment. Methods: Seven cases of Sprengel's deformity of Cavendish grade 3 or 4 were treated surgically and then clinically evaluated and examined using three-dimensional computed tomography (3D CT). (Two boys and five girls aged 50.9 ± 15.4 months, mean ± standard deviation at the time of operation.) The mean follow-up was 53.1 months (range, 12 to 92 months). After the omovertebral bone and the superomedial side of the scapula were removed, the levator scapulae and rhomboids were reattached to wrap around the scapula at maximum upward rotation to assist in maintaining this position. Cavendish and Rigault grades were used for evaluation of postoperative appearance. The superior displacement and rotation of the scapula were measured on the trunk posterior view using 3D CT. The relationship between improvement in the range of motion and radiologic change were analyzed statistically. Results: The postoperative flexion (97.9° ± 12.9° to 160° ± 11.5°) and abduction (99.3° ± 13.0° to 161.4° ± 15.7°) were significantly improved compared with the mean preoperative values (P < .0001). 3D CT revealed that in all patients the malrotation of the scapula was improved postoperatively. The current study shows that successful realignment of the scapula led to these improved clinical results. Conclusions: Our procedure has advantages not only for recovery of the range of motion but also for reducing the characteristic lump in the web of the neck. However, our procedure has an inherent limitation related to asymmetrical shoulder level and width. 3D CT may be useful for preoperative planning and postoperative evaluation.

for 2013 International Investigative Dermatology Meeting, Edinburgh International Conference Centre, Edinburgh, Scotland, May 8 – 11, 2013

Background: Lung tumors showing ground-glass opacities on high-resolution computed tomography indicate the presence of inflammation, atypical adenomatous hyperplasia, or localized bronchioloalveolar carcinoma. We adopted a two-staged video-assisted thoracoscopic lobectomy strategy involving completion lobectomy for localized bronchioloalveolar carcinoma with an invasive component according to postoperative pathological examination by permanent section after partial resection. Methods: Forty-one patients with undiagnosed small peripheral ground-glass opacity lesions underwent partial resection from 2001 to 2007 in Hokkaido University Hospital. Localized bronchioloalveolar carcinoma was classified according to the Noguchi classification for adenocarcinoma. Malignant lesions other than Noguchi types A and B were considered for completion lobectomy and systemic mediastinal lymphadenectomy. Perioperative data of completion video-assisted thoracoscopic lobectomies were compared with data of 67 upfront video-assisted thoracoscopic lobectomies for clinical stage IA adenocarcinoma performed during the same period. Results: Postoperative pathological examination revealed 35 malignant and 6 non-malignant diseases. Histologically, all of the malignant diseases were adenocarcinomas of Noguchi type A (n = 7), B (n = 9), C (n = 18), and F (n = 1). Eleven of 19 patients (58%) with Noguchi type C or F underwent two-staged video-assisted thoracoscopic lobectomy. Three patients refused a second surgery. There was no cancer recurrence. The two-staged lobectomy group had a significantly longer operative time and more blood loss than the upfront lobectomy group. There was no surgical mortality or cancer recurrence. Conclusions: Two-staged lobectomy for undiagnosed small peripheral ground-glass opacity lesions showed satisfactory oncological results. However, low compliance for and invasiveness of the second surgery are concerns associated with this strategy.

Background: A double-network (DN) gel, which is composed of poly(2-acrylamido-2-methylpropanesulfonic acid) and poly(N,N'-dimethyl acrylamide), can induce hyaline cartilage regeneration in vivo in a large osteochondral defect. The purpose of this study was to clarify the influence of the thickness of the implanted DN gel on the induction ability of hyaline cartilage regeneration. Methods: Thirty-eight mature rabbits were used in this study. We created an osteochondral defect having a diameter of 4.3-mm in the patellofemoral joint. The knees were randomly divided into 4 groups (Group I: 0.5-mm thick gel, Group II: 1.0-mm thick gel, Group III: 5.0-mm thick gel, and Group IV: untreated control). Animals in each group were further divided into 3 sub-groups depending on the gel implant position (2.0-, 3.0-, or 4.0-mm depth from the articular surface) in the defect. The regenerated tissues were evaluated with the Wayne's gross and histological grading scales and real time PCR analysis of the cartilage marker genes at 4 weeks. Results: According to the total Wayne's score, when the depth of the final vacant space was set at 2.0 mm, the scores in Groups I, II, and III were significantly greater than that Group IV (p < 0.05), although there were no significant differences between Groups I and IV at a 3.0-mm deep vacant space. The expression levels of type-2 collagen in Groups II and III were significantly higher (p < 0.05) than that in Group IV. Conclusions: The 1.0-mm thick DN gel sheet had the same ability to induce hyaline cartilage regeneration as the 5.0-mm thick DN gel plug. However, the induction ability of the 0.5-mm thick sheet was significantly lower when compared with the 1.0-mm thick gel sheet. The 1.0-mm DN gel sheet is a promising device to establish a cell-free cartilage regeneration strategy that minimizes bone loss from the gel implantation.

An intraductal papillary neoplasm of the bile duct is a biliary, epithelium-lined, cystic lesion that exhibits papillary proliferation and rarely causes large hemorrhagic cystic lesions. Here, we report a case of an intraductal papillary neoplasm of the bile duct mimicking a hemorrhagic hepatic cyst in a middle-aged man with large hemorrhagic hepatic cysts who experienced abdominal pain and repeated episodes of intracystic bleeding. Following portal vein embolization, extended right hepatic lobectomy was performed, and intraoperative cholangiography revealed communication between the intracystic space and the hepatic duct. Although histological studies revealed that the large hemorrhagic lesion was not lined with epithelium, the surrounding multilocular lesions contained biliary-derived epithelial cells that presented as papillary growths without ovarian-like stroma. A diagnosis of oncocytic-type intraductal papillary neoplasm of the bile duct was made, and we hypothesized that intracystic bleeding with denudation of the lining epithelial cells might occur as the cystically dilated bile duct increased in size. Differential diagnosis between a hemorrhagic cyst and a cyst-forming intraductal papillary neoplasm of the bile duct with bleeding is difficult. However, an intraductal papillary neoplasm of the bile duct could manifest as multilocular hemorrhagic lesions; therefore, complete resection should be performed for a better prognosis.

An early identification of the tumor response to sorafenib treatment is indispensable for selecting optimal personalized treatment strategies. However, at present, no reliable predictors are clinically available. F-18-fluorothymidine (F-18-FLT) positron emission tomography (PET) is used to assess tumor proliferation, since the FLT uptake level reflects thymidine kinase-1 (TK-1) activity. Thus, the present study determined whether FLT was able to evaluate the early tumor response to sorafenib treatment in a human renal cell carcinoma (RCC; A498) xenograft in comparison with the tumor proliferation marker, Ki-67. Mice bearing A498 tumors were assigned to the control and sorafenib-treated groups and the tumor volume was measured every day. [Methyl-3H(N)]-3'-fluoro-3'-deoxythymidine (H-3-FLT) was injected 2 h prior to the sacrifice of the mice on days three and seven following the treatment. H-3-FLT autoradiography (ARG) and Ki-67 immunohistochemistry (IHC) were performed using adjacent tumor sections. In the visual assessment, the intratumoral H-3-FLT uptake level diffusely increased following the treatment, while no significant changes were observed in Ki-67 IHC. The intratumoral H-3-FLT uptake levels significantly increased by 2.7- and 2.6-fold on days three and seven following the treatment, while the tumor volume and Ki-67 index did not significantly change. Thus, an increased FLT uptake level was demonstrated following the treatment, which may indicate the suppression of thymidylate synthase (TS) and the compensatory upregulation of TK-1 activity by sorafenib.

Neuromelanin-sensitive MRI has been reported to be used in the diagnosis of Parkinson's disease (PD), which results from loss of dopamine-producing cells in the substantia nigra pars compacta (SNc). In this study, we aimed to apply a 3D turbo field echo (TFE) sequence for neuromelanin-sensitive MRI and to evaluate the diagnostic performance of semi-automated method for measurement of SNc volume in patients with PD. We examined 18 PD patients and 27 healthy volunteers (control subjects). A 3D TFE technique with off-resonance magnetization transfer pulse was used for neuromelanin-sensitive MRI on a 3T scanner. The SNc volume was semi-automatically measured using a region-growing technique at various thresholds (ranging from 1.66 to 2.48), with the signals measured relative to that for the superior cerebellar peduncle. Receiver operating characteristic (ROC) analysis was performed at all thresholds. Intra-rater reproducibility was evaluated by intraclass correlation coefficient (ICC). The average SNc volume in the PD group was significantly smaller than that in the control group at all the thresholds (P < 0.01, student t test). At higher thresholds (> 2.0), the area under the curve of ROC (Az) increased (0.88). In addition, we observed balanced sensitivity and specificity (0.83 and 0.85, respectively). At lower thresholds, sensitivity tended to increase but specificity reduced in comparison with that at higher thresholds. ICC was larger than 0.9 when the threshold was over 1.86. Our method can distinguish the PD group from the control group with high sensitivity and specificity, especially for early stage of PD.