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Purpose To determine the differences in the scar tissue formation during the healing of the repaired retracted cuff tear from that of the nonretracted tear. Methods Eighteen right rabbit shoulders received a 1-cm transverse cuff incision over the footprint to simulate “nonretracted cuff tears” before the transosseous repairs (group A). A 1-cm tendinous portion was excised from 18 left shoulders to create defects to simulate “retracted cuff tears” before repairing the defects (group B). At week 12 postrepair, 20 and 16 shoulders underwent histologic and biomechanical analyses, respectively. Eight shoulders were used as a control group for biomechanical analyses. Results All specimens showed good healing and continuity of the repaired tendons. At low magnification, fibrous tissue firmly held the tendon-to-bone junctions in group A; however, all specimens in group B showed medially retracted tendons with fibrous tissue continuity between the tendon stumps and footprints. At medium magnification, more irregular collagen fiber orientation was observed in group B. Polarized light microscopy showed fibrous tissue continuity with medially retracted tendons in group B. When we quantified collagen fiber orientation using ImageJ software, group B had inferior grayscale measurements when compared with group A (P = .001). At week 12, no statistical differences existed in mean loads-to-failure at the repair sites between the groups (P = .783). Conclusions In the nonretracted cuff tears, fibrous tissue bound the tendon-to-bone junction with healing. After the healing of the retracted cuff tears, continuity of nontendinous tissue was observed adjacent to the medially retracted tendon, which comprised more disorganized immature fibrous tissue than that in the nonretracted cuff tears. Clinical Relevance Unlike the healing of nonretracted rotator cuff tear, repairing of the “retracted” tendon end of cuff tear still resulted in retraction of the tendon back to its original position but being held down with fibrous tissue to the footprint.

Context. Denosumab is a monoclonal antibody against RANK ligand. Its administration in giant cell tumor of bone (GCTB) cases results in elimination of giant cells and new bone formation. Neoplastic stromal cells of GCTB harbor mutation of histone 3.3 and have pre-osteoblastic properties and thus express SATB2. Objectives. To (1) analyze histological changes in post-denosumab–treated GCTB, (2) analyze expression of H3.3G34W and SATB2 in pre- and post-denosumab–treated samples, and (3) to discuss why changes occur in the expression of not only H3.3G34W but also SATB2. Materials and Methods. Hematoxylin and eosin slides of 19 cases of denosumab-treated GCTB were reviewed. Immunohistochemical stains H3.3G34W and SATB2 were performed. The number of positive mononuclear cells were counted and graded. Results. Complete absence of osteoclast-like giant cells (OCLGCs) was noted in most cases along with a fibro-osseous component merging with peripheral shell of reactive bone. Irregular trabeculae of woven bone and osteoid with focal osteoblastic rimming was seen. Spindle cells were arranged predominantly in fascicular pattern. Morphometric analysis of H3.3G34W showed a mean of 68.8% positive stromal cells in pretreatment and a mean of 26.9% positive stromal cells in posttreated specimens with a statistically significant P value (.001). Mean percentage of SATB2-positive stromal cells in the pre- and posttreatment specimens was 36.46% and 20.8%, respectively. Conclusions. Our study validates that denosumab treatment results in marked reduction of OCLGCs with increased osteoblastic activity. Decreased expression of H3.3G34W in posttreatment may be a result of decreased antigenicity of neoplastic mononuclear cells. No significant change in SATB2 expression was noted.

Ewing sarcoma (ES) is the second most common primary malignant bone tumour, mainly occurs in children and adolescents, and has an overwhelming mortality. Despite extensive studies, few effective oncogenic signals have been described. Therefore, it is crucial to exploit novel pathognomonic factors and targetable biomarkers for ES patients. Based on previous studies, we speculate that insulin-like growth factor 1 receptor (IGF1R), which is upregulated by early growth response 1 (EGR1), may play a pivotal role in strengthening the downward transmission of IGF1 cascades. Therefore, in this study, we concentrated on determining the pathogenetic contribution of EGR1 in diverse ES cells. This report is the first to study the pathogenic role of EGR1 in ES. ES cells were cultured and transfected with Stealth RNAi human EGR1 small interfering RNA (siRNA) or negative control. Cell proliferation and invasion potential were measured. mRNA and protein expression of EGR1, IGF1R, and EWS-FLI1 also were assessed. In all EGR1 siRNA-transfected cells (SK-ES-1, RD-ES, and HS863.T), cell proliferation and invasive potential decreased significantly in EGR1 siRNA-transfected ES cells. mRNA and protein expression for EGR1, IGF1R, and EWS-FLI1 were also significantly reduced. In conclusion, EGR1 upregulated IGF1R expression and enhanced the expression of the oncogenic fusion protein EWS-FLI1. The EWS-FLI1/EGR1/IGF1R cascade combined with the previously confirmed pathways can form a speculative circuit, implicating positive feedback for tumourigenesis in ES. Therefore, EGR1 inhibitors are expected to be useful for the treatment of ES by preventing oncogenic IGF1/IGF1R expression.

Giant cell tumor of bone (GCTB)-related clonal aberrations occur in a background of epigenetic histone modifications (especially the G34W mutation of H3F3A gene) that induce cytogenetic abnormalities. Clonal aberrations are closely linked to the aggressiveness of GCTB. The "neoplastic" mononuclear stromal cells in GCTB express fundamental RANKLs and various chemokines and cytokines associated with monocyte recruitment and "reactive" multinucleated giant cells (osteoclastogenesis). The reciprocal and orchestrated actions between mononuclear stromal cells and multinucleated giant cells help in the understanding of the molecular pathogenesis and tumor biology of GCTB. In the future, novel targets in the updated tumor biology and molecular pathogenesis of GCTB should be explored and scrutinized for the development of systemic therapy.

Summary: Background/Objective: The purpose of this study was to assess the impact of circumferential tumor location on circumferential resection margin (CRM) status and the depth of tumor invasion in mid and low rectal cancer. Methods: We retrospectively analyzed whole-mount slides of 58 patients who underwent total mesorectal excision for mid and low rectal cancer. The rate of tumor-positive CRM was compared according to the circumferential tumor location. In 31 patients, morphometric analyses of whole-mount specimens were performed to measure the depth of tumor invasion according to circumferential tumor location. Results: Among 58 patients, 50% of tumors were anterior tumor and 50% were nonanterior. A tumor-positive CRM was more observed frequently in anterior tumors than in nonanterior tumors (41.1% vs. 10.3%, p = 0.007). In a multivariate analysis, anterior tumor was the only independent risk factor for a positive CRM (odds ratio 4.725, 95% confidence interval 1.102–20.261, p = 0.037). In a morphometric analysis of 31 patients, the depth of tumor invasion from the muscularis mucosa was greater (11.9 mm vs. 6.6 mm, p = 0.028) in those with anterior tumors. Conclusion: Anterior tumors are associated with a higher risk of tumor-positive CRM and tend to exhibit deeper invasion in mid and low rectal cancer. Keywords: circumferential resection margin, depth of invasion, rectal cancer, tumor location

Objective: Tumor-induced osteomalacia is a paraneo-plastic syndrome characterized by renal phosphate wasting that results in hypophosphatemia and osteomalacia. Tumor-induced osteomalacia is typically associated with benign mesenchymal tumors arising in the bone and soft tissue. Here, we describe a case of tumor-induced osteomalacia associated with an organizing hematoma.Methods: Medical records were reviewed.Results: A 54-year-old, Asian woman presented with progressive pain in the thighs and pelvis for a year that eventually led to a waddling gait. Laboratory examinations showed hypophosphatemia, hyperphosphaturia, normocalcemia, elevated serum alkaline phosphatase levels, and decreased serum calcitriol levels. The patient's bone mineral density was low, and the bone scan showed increased uptake throughout the skeleton. A bone biopsy contained excessive osteoid. We found a palpable mass on her left flank, which had been detected 2 years previously after doing a hula hoop exercise. Computed tomography showed a heterogeneously enhanced, subcutaneous mass in the left-lateral abdominal wall. We resected the mass and it was identified as a phosphaturic mesenchymal tumor with an organizing hematoma. After surgery, her serum phosphorus level returned to normal, and her thigh and pelvis pain improved.Conclusion: Since a hematoma-associated lesion can be a source of phosphaturic agents, any previous history of injuries should be carefully explored in suspected cases of tumor-induced osteomalacia.Abbreviations: PMT phosphaturic mesenchymal tumor TIO tumor-induced osteomalacia

Because Mg-Ca-Zn alloys are biodegradable and obviate secondary implant removal, they are especially beneficial for pediatric patients. We examined the degradation performance of Mg-Ca-Zn alloys depending on the surface modification and investigated the in vivo effects on the growth plate in a skeletally immature rabbit model. Either plasma electrolyte oxidation (PEO)-coated (n = 18) or non-coated (n = 18) Mg-Ca-Zn alloy was inserted at the distal femoral physis. We measured the degradation performance and femoral segment lengths using micro-CT. In addition, we analyzed the histomorphometric and histopathologic characteristics of the growth plate. Although there were no acute, chronic inflammatory reactions in either group, they differed significantly in the tissue reactions to their degradation performance and physeal responses. Compared to non-coated alloys, PEO-coated alloys degraded significantly slowly with diminished hydrogen gas formation. Depending on the degradation rate, large bone bridge formation and premature physeal arrest occurred primarily in the non-coated group, whereas only a small-sized bone bridge formed in the PEO-coated group. This difference ultimately led to significant shortening of the femoral segment in the non-coated group. This study suggests that optimal degradation could be achieved with PEO-coated Mg-Ca-Zn alloys, making them promising and safe biodegradable materials with no growth plate damage.

Since the dysregulation of ribosome biogenesis is closely associated with tumor progression, in the current study, the critical role of ribosome biogenesis related signaling was investigated in melatonin and/or puromycin induced apoptosis in MDA-MB-231 breast cancer cells. Despite its weak cytotoxicity, melatonin from 3 mM attenuated the expression of 45S pre-ribosomal RNA (pre-rRNA), UBF as a nucleolar transcription factor, and fibrillarin at mRNA level and consistently downregulated nucleolar proteins such as UBF and fibrillarin at protein level in MDA-MB-231 cells. Furthermore, immunofluorescence assay revealed that UBF was also degraded by melatonin in MDA-MB-231 cells. In contrast, melatonin attenuated the expression of survival genes such as Bcl-xL, Mcl-1, cyclinD1, and cyclin E, suppressed the phosphorylation of AKT, mTOR, and STAT3, and cleaved PARP and activated caspase 3 only at a high concentration of 12 mM. However, combined treatment of melatonin (3 mM) and puromycin (1 μM) synergistically inhibited viability, attenuated the expression of 45S pre-rRNA and UBF, and consistently downregulated UBF, XPO1 and IPO7, procaspase 3, and Bcl-xL in MDA-MB 231 cells. Overall, these findings suggest that melatonin can be a cancer preventive agent by combination with puromycin via the inhibition of 45S pre-rRNA and UBF in MDA-MB 231 breast cancer cells.

Summary Purpose Tumor-associated macrophages (TAMs) play a significant role in tumor progression and angiogenesis. However, the prognostic value of TAMs in different histologic locations of gastric cancer (GC) is still unknown. We evaluated the distribution of TAMs in different histologic locations to investigate its importance in predicting prognosis and the relationship with angiogenesis and CXCL12 expression in GC. Methods and materials The distribution of TAMs and microvessel density (MVD) in 113 GC samples were evaluated by immunohistochemical staining of CD163 and CD105, respectively. The extent of TAM distribution in the tumor was categorized into three groups: infiltrated TAMs in the tumor nest (TN), tumor stroma (TS) and invasive tumor margin (TM). The expression of CXCL12 in GC were evaluated by immunohistochemical staining of tissues from 88 GC samples. Results The increased CD163+ TAMs in TS and TM were closely correlated with tumor size, depth of invasion, TNM stage, lymph node metastasis, and lymphovascular invasion. TAMs in TN was not related with any clinicopathologic characteristics except histologic differentiation. The high infiltration of CD163+ TAMs in TS and TM were significantly correlated with poor overall survival. Regardless of location, CD163+ TAMs were significantly correlated with increased MVD. CXCL12 expression was significantly associated with increased CD163+ TAMs in TS and TM. Conclusions TAMs in different histologic locations in GC were related to distinct aspects of tumor progression. CD163+ TAMs in TS and TM are associated with tumor progression and CXCL12 expression in GC. TAMs may be involved in tumor progression through the angiogenesis.

Amyloidosis is a disease characterized by the deposition of non-soluble fibrous protein in multiple tissues with a number of possible causes. This protein deposition can occur in any tissue, yet is most commonly seen in kidneys, heart, and gastrointestinal tracts. However, invasion to bone tissues is not often reported. The deposition of amyloid proteins in bone tissues may result in joint pain and pathological fractures; it is important to elucidate the causes and detect early to determine prognosis and treat optimally. In the present case report, with relevant literature review, the authors report a case of total hip arthroplasty in an amyloidosis patient.

The objective of the present study was to determine whether guanine nucleotide-binding protein α stimulating (GNAS) gene expression correlates with pathognomonic signs by analyzing the mutations, methylation status and G-protein α subunit (Gsα) expression of GNAS in Ewing sarcoma (ES). Formalin-fixed paraffin-embedded tissue samples from 77 patients with primary ES were obtained in South Korea, Argentina and Brazil, and were studied via methylation chip assay and direct sequencing of the GNAS gene and immunohistochemical analysis of Gsα. The mutation and methylation statuses of the GNAS gene were examined. Immunohistochemical results were measured with respect to proportion and staining intensity. The results revealed that GNAS genes in ES tumor samples were less methylated compared with normal controls. No mutations were detected at exons 8 or 9 of the GNAS locus complex on chromosome 20q13.3, indicating that the pathogenesis of ES was not associated with GNAS mutation. Gsα expression correlated well with the methylation status of the GNAS gene. Notably, high Gsα expression was detected more frequently in samples from living patients than from decedents, although this was not statistically significant (P=0.055). In conclusion, GNAS mutation is not associated with the pathogenesis of ES tumors. This finding may be used to differentiate ES tumors from metastatic bone lesions with morphological similarity to ES tumors. Analysis of the methylation status of the GNAS gene and immunohistochemical Gsα expression suggests that hypermethylated GNAS (low Gsα expression) in ES may be associated with unfavorable progression with a non-significant trend.

A 13-year-old Korean girl presented with a 7-year history of a pruritic, light-brown patch containing multiple 0.2- to 0.5-cm brownish-to-reddish maculopapules on the left anterior chest. When her skin was rubbed, the lesion became itchy and red. Histopathologic evaluation demonstrated marked dense dermal infiltration of mast cells. We report a rare case of atypical maculopapular cutaneous mastocytosis with clinical features similar to those of nevus spilus.

Background: Isocitrate dehydrogenase (IDH) catalyzes the oxidative decarboxylation of isocitrate to yield α-ketoglutarate (α-KG) with production of reduced nicotinamide adenine dinucleotide (NADH). Dysfunctional IDH leads to reduced production of α-KG and NADH and increased production of 2-hydroxyglutarate, an oncometabolite. This results in increased oxidative damage and stabilization of hypoxia-inducible factor α, causing cells to be prone to tumorigenesis. Methods: This study investigated IDH mutations in 61 Ewing sarcoma family tumors (ESFTs), using a pentose nucleic acid clamping method and direct sequencing. Results: We identified four cases of ESFTs harboring IDH mutations. The number of IDH1 and IDH2 mutations was equal and the subtype of IDH mutations was variable. Clinicopathologic analysis according to IDH mutation status did not reveal significant results. Conclusions: This study is the first to report IDH mutations in ESFTs. The results indicate that ESFTs can harbor IDH mutations in previously known hot-spot regions, although their incidence is rare. Further validation with a larger case-based study would establish more reliable and significant data on prevalence rate and the biological significance of IDH mutations in ESFTs.

We set out to investigate the cause of persistently increased signal intensity (SI) in the posterior portion of the proximal patellar tendon (pPT) on T1-weighted images (T1WI). MR imaging was performed in eight cadavers, followed by gross histological examination. In addition, 84 patients without trauma history or anterior knee pain were included to compare the SI of the PTs. The patients were divided according to their age, sex, and Kellgren-Lawrence (KL) grades. The length and thickness of the increased SI portion in the pPT and whole PT (wPT) on T1WI were recorded. Histological specimens demonstrated that the adipose tissue, vessels, and perivascular connective tissue invaginated into the posterior portion of the pPT. This histological anatomy corresponded to the pPT signal change on MR imaging. There was linear and interdigitating increased SI of the pPT in all of the 84 patients (100 %). There were no differences in the lengths and thicknesses of the increased SI portion of pPTs and wPTs according to age, sex, and KL grade (all p > 0.05). The increased SI of the pPT on T1WI and fluid-sensitive MR images results from invaginating fat, vessels, and perivascular connective tissue. It is not pathological, but a normal and common finding. • Increased linear/interdigitated SIs of the pPT is a normal and common finding. • Invaginated adipose tissue, vessels, and connective tissue could contribute to increased SI. • The fibrocartilage has a minimal role in increased SI of the pPT. • Age, sex, and KL grade do not significantly influence the increased SI. • Knowledge of this increased SI should help clinicians to avoid unnecessary treatment.

Beclin-1 induces autophagy, which is known to be involved in many physiopathological processes such as cell development, aging, stress response, immune response and cancer. Several studies showed that Beclin-1 expression is associated with several prognostic factors of gastric carcinomas. Recently, the connection between autophagy and the hedgehog (HH) signaling pathway has been studied. Here, we investigated the relationship between the autophagy and hedgehog (HH) signaling pathways in gastric adenocarcinoma. We evaluated Beclin-1 and Gli2 expression in 108 gastric adenocarcinoma tissues via immunohistochemical analysis, using a tissue microarray, in relation to survival and other prognostic factors. Our results show that increased Beclin-1 expression is correlated with favorable clinicopathological variables including histologic grade, tumor size, primary tumor (T) stage, lymph node metastasis, lymphatic invasion, neural invasion, and tumor recurrence. Furthermore, increased Gli-2 expression was correlated with several favorable clinicopathological variables including primary tumor (T) stage, lymphatic invasion, and tumor recurrence. Increased Beclin-1 expression was significantly correlated with increased Gli2. Univariate analyses for disease-free survival and overall survival revealed that the higher Beclin-1 and Gli2 expression group had a more favorable prognosis compared with the lower Beclin-1 and Gli2 expression group. Our results suggest that progressively increased Beclin-1 and Gli2 expression contributes to the inhibition of tumor growth and metastasis in gastric adenocarcinoma and Beclin-1 acts as a tumor suppressor by regulating the HH signaling pathway through Gli2 expression in gastric adenocarcinoma.

Osteosarcoma is the most common malignant bone tumor in children and characterized by aggressive biologic behavior of metastatic propensity to the lung. Change of treatment paradigm brings survival benefit; however, 5-year survival rate is still low in patients having metastastatic foci at diagnosis for a few decades. Metastasis-associated protein (MTA) family is a group of ubiquitously expressed coregulators, which influences on tumor invasiveness or metastasis. MTA1 has been investigated in various cancers including osteosarcoma, and its overexpression is associated with high-risk features of cancers. In this review, we described various molecular studies of osteosarcoma, especially associated with MTA1.

DNA hypermethylation plays a major role in the regulation of gene expression in differentiation, development and diseases. The DNA mismatch repair system, which includes Mut-S-Homologon-2 (MSH2) protein, is essential to maintain the stability of the genome during repeated duplication. This study aimed to investigate tumoral MSH2 immunohistochemical expression in clear cell renal cell carcinoma (RCC), and the associations between tumoral MSH2 immunohistochemical expression and clinicopathological parameters. Previously, we reported a high-throughput method for analyzing the methylation status of 807 preselected genes; Illumina’s GoldenGate Methylation Cancer Panel I microarray. The MSH2 gene was identified to be hypermethylated in cancer tissue compared with normal tissue. From January 2000 to December 2012, 129 clear cell RCC cases (median age, 61 years) were included in the immunohistochemical analysis of the present study. Patients were divided according to MSH2 expression status (MSH2-negative, n=53; MSH2-positive, n=76). T stage was significantly higher in the MSH2-negative group than in the MSH2 positive-group (P=0.021). There was no significant difference in terms of N stage, M stage and Fuhrman’s nuclear grade between the MSH2-negative and MSH2-positive group (N stage, P=0.072; M stage, P=0.759; Fuhrman’s nuclear grade, P=0118). The MSH2-negative group showed decreased rates of recurrence-free survival, progression-free survival and overall survival, without statistically significant results (P=0.232, P=0.268 and P=0.311, respectively). MSH2 protein expression may be a useful marker for predicting TNM stage and prognosis and, thus, MSH2 may be a prognostic factor in clear cell RCC.

Chemokines are a family of peptide mediators that play an essential role in cellular migration and intracellular communication in tumor cells as well as immune cells. We hypothesized that the CXCL16-CXCR6 ligand-receptor system plays an important role in Ewing sarcoma (ES) family tumor (ESFT) progression. Using real-time quantitative reverse transcription-polymerase chain reaction, we investigated the mRNA expression of CXCL16, CXCR6, and ADAM 10 in various cell lines. We also investigated the expression of CXCL16, CXCR6, ADAM 10, and ADAM 17 in tissue samples from 61 ESFT patients using immunohistochemistry. The mRNA expression levels of CXCL16 and CXCR6 in the ES cell line were higher than those in the other cell lines. Immunohistochemical staining revealed that CXCL16 and CXCR6 were highly expressed in tumor cells of ESFT and showed a positive correlation between them. The expression of CXCL16 and CXCR6 was associated with the occurrence of lung metastasis. Univariate analysis revealed that CXCL16 or CXCR6 expression was associated with worse prognosis of ESFT patients. In addition, CXCL16 and CXCR6 expression was associated with shorter overall survival irrespective of other prognostic factors. Our results suggest that the CXCL16/CXCR6 axis appears to be important in the progression of ESFT, resulting in more aggressive clinical behavior. Furthermore, there may be a decrease in the overall survival in ESFT patients who have tumors that stain strongly for CXCL16 and CXCR6.

FOXP3 is a transcription factor and a well-known hallmark of immune suppressive T regulatory cells. Recent studies indicate that in tumor cells, FOXP3 plays an important role in tumor development in addition to its well-established Treg function in the immune system. We investigated tumoral FOXP3 expression in breast carcinoma, and the relationships between tumoral FOXP3 expression and p53, HER-2/ErbB2, Ki67, infiltrated Tregs, and other clinicopathological variables. Tissue samples from 272 cases of breast carcinoma were used. We assessed tumoral FOXP3, p53, HER-2/ErbB2, Ki67, and infiltrated Tregs using immunohistochemical staining. Positive expression of tumoral FOXP3 was observed in 38.6% (105/272) of breast carcinomas. Positive tumoral FOXP3 expression was significantly related with positive p53 and higher Ki67 expression. Higher histological grade was significantly correlated to increased tumoral FOXP3 expression. Tumoral FOXP3 expression was positively correlated with infiltrated FOXP3-expressing Tregs. From these data, we argue that tumoral FOXP3 has a potential oncogenic function in conjunction with the p53 tumor suppressor protein and infiltrated Tregs in human breast carcinomas.

Recent studies suggest that dysregulated innate immunity plays an important role in the pathogenesis of immunoglobulin A nephropathy (IgAN). The interleukin-20 subfamily and its receptor, interleukin-22 receptor alpha-1 (IL-22R1), were recently identified as immunomodulators in human diseases, acting as mediators of mucosal host defense. However, the potential role of IL-22R1 in the pathogenesis of IgAN has not been explored. In the current study, 194 patients with IgAN and 287 normal controls were genotyped for coding polymorphisms of the IL-22R1 gene and the association between the polymorphisms and IgAN was investigated. Local expression of IL-22R1 was examined in patients with IgAN and healthy controls using immunohistochemistry. Our case-control analysis showed that genotypes of rs3795299 were associated with childhood IgAN. Individuals with the CC genotype of rs3795299 had about 3-fold reduced risk of IgAN compared with those with the GG genotype in the codominant model (P=0.0028) and those with the genotypes containing the G allele (GG or GC) in the recessive model (P=0.002). After Bonferroni correction, the association between the rs3795299 CC genotype and reduced risk of developing IgAN remained significant. Furthermore, the renal expression of IL-22R1 was significantly higher in healthy controls compared with subjects with IgAN. Our data suggest that the CC genotype of rs3795299 polymorphism in the IL-22R1 gene is associated with the reduced risk of IgAN, and this genetic association was supported by the higher renal expression of IL-22R1 in healthy controls compared with patients with IgAN.

Nasal polyps can be categorized as eosinophilic or non-eosinophilic, depending on inflammatory cell infiltration. There are geographical differences in the prevalence of types of pathologic polyps. The aim of this study was to evaluate the change in the prevalence of histological subtypes of polyps over time in a Korean population.A retrospective cross-sectional study with histologic analysis.A single academic medical center.A total of 230 patients with nasal polyps were enrolled between 1993-1994 (group A) and 2010-2011 (group B). Specimens were fixed in formalin and embedded into paraffin blocks. Slides were stained with hematoxylin-eosin (HE) and were subsequently reviewed by 2 of the authors. The numbers of eosinophils per high power field (HPF), as well as other cellular, epithelial, and stromal markers, were recorded.We compared nasal polyp eosinophil counts according to time period. The average eosinophil count/HPF increased from 6.8 in group A to 19.3 in group B (P = .006). The prevalence of eosinophilic polyps also increased from 24.0% in group A to 50.9% in group B (P.001). Among other histologic markers, lymphocytes, basement membrane thickening, and gland hyperplasia showed significant differences between groups.After comparison of histopathologic findings of nasal polyps from 1993 and 2011 at 1 academic medical center in Korea, the prevalence of eosinophilic nasal polyps, which are known to be rare among Asians, has significantly increased.

In this study, an efficient analytical model for the dynamic analysis of tall buildings with a shear wall-frame structural system has been proposed. A shear wall-frame structural system usually consists of a core wall showing flexural behavior and a frame presenting shear behavior. Therefore, the deformed shape of the shear wall-frame structural system is shown by the combination of flexural mode and shear mode. These characteristics should be considered when an efficient analytical model is developed. To this end, the effect of shear wall and frame on the dynamic behavior of a tall building with a dual system has been separately investigated. In this study, the structural characteristics of a separated individual shear wall model and the frame model without shear wall has been evaluated. In order to consider the effect of the shear wall in the frame model without shear wall, a rigid body was used instead of the shear wall. Each equivalent model for the separated shear wall part and frame part has been independently developed and two equivalent models were then combined to create an efficient analytical model for tall buildings with a shear wall-frame structural system. In order to verify the efficiency and accuracy of the proposed method, time history analyses of tall buildings with a shear wall-frame system were performed. Based on analytical results, it has been confirmed that the proposed method can provide accurate results, requiring significantly reduced computational time and memory

In a shear wall-frame structural system, the structural response is determined by the interaction between the shear wall in bending mode and the frame in shear mode. In order to effectively consider these characteristics of a shear wall-frame structure, the simplified numerical model using the T-shape rigid body was suggested in the previous study. Based on the previously proposed model, an efficient numerical model for a wall-frame structure with an eccentric core has been proposed in this study. To this end, the previously proposed 2D model is extended to the 3D model and it is enhanced by considering torsion effects. As a result, the enhanced model can be applied to the analysis of a wall-frame structure with an eccentric core as well as a centric core.

SUMMARY In this study, an efficient analytical model for the dynamic analysis of tall buildings with a shear wall–frame structural system has been proposed. A shear wall–frame structural system usually consists of a core wall showing flexural behavior and a frame presenting shear behavior. Therefore, the deformed shape of the shear wall–frame structural system is shown by the combination of flexural mode and shear mode. To consider this characteristic in developing an efficient analytical model, the effect of shear wall and frame on the dynamic behavior of a tall building with a dual system has been separately investigated. In order to consider the effect of the shear wall in the frame model without shear wall, a rigid body was used instead of the shear wall. Each equivalent model for the separated shear wall part and frame part has been independently developed, and two equivalent models were then combined to create an efficient analytical model for tall buildings with a shear wall–frame structural system. In order to verify the efficiency and accuracy of the proposed method, time history analyses of tall buildings with a shear wall–frame system were performed. With analytical results, it has been confirmed that the proposed method can provide accurate results with significantly reduced computational time and memory. Copyright © 2013 John Wiley & Sons, Ltd.

Heterotopic ossification occurring in colon cancer is an exceedingly rare event. The pathogenetic mechanism of tumor-related heterotopic bone formation remains unclear. Herein, we describe a rare case of colon cancer with ossification in a 76-year-old woman. We also highlight the etiology of heterotopic ossification by immunohistochemical evaluation of novel markers such as bone morphogenetic protein 9 (BMP9), osteocalcin, osteopontin, and β-catenin. BMP9 is one of the most potent osteogenetic BMPs. However, no previous research has been performed concerning BMP9 in heterotopic ossification arising in colon cancer. Subsequently, we suggest a hypothesis of tumor-associated heterotopic bone formation through this case. When osteoblastic indicators including BMP9, osteocalcin, and osteopontin are upregulated in tumor cells, osteoblast-like transformation of such tumor cells occurs. These tumor cells augment the release of interactive osteogenetic factors (BMP9, osteocalcin, and osteopontin) and stimulate uncommitted mesenchymal stromal cells into specific osteoblastic differentiation, contributing to heterotopic bone formation. This transformation of tumor cells is considered a type of epithelial-mesenchymal transition (EMT) because of overexpression of BMP9 and β-catenin. Patients should be followed closely because EMT has a tendency toward local recurrence. Our findings provide insight into the pathogenetic etiology of heterotopic ossification in colon cancer.

Epiphyseal involvement of a simple bone cyst (SBC) is rare. Furthermore, its pathological variant is even more uncommon. Herein, we report a case of a 22-year-old woman with an SBC containing unusual mesenchymal tissue proliferation with epiphyseal involvement in the proximal fibula. Magnetic resonance imaging showed a cystic lesion that involved the entire epiphysis as well as some soft tissue components. Hence, our initial differential diagnosis did not include SBC. However, pathology confirmed a SBC. Thus, SBC should be considered in the diagnosis of cystic lesions despite the atypical imaging findings.

Heterotopic ossification occurring to low-grade appendiceal mucinous neoplasm (LAMN) (pseudomyxoma peritonei) is extremely rare. The pathogenetic mechanism of the tumor-related heterotopic bone formation remains as yet unconfirmed. Here, we describe a rare case of LAMN with ossification in a 72-year-old woman, and concentrate on the etiology of heterotopic ossification by the immunohistochemical evaluation of the novel markers such as BMP9, osteocalcin, and osteopontin. BMP9 is one of the most effective osteogenetic proteins. However, no researches associated with BMP9 in the heterotopic ossification occurring to LAMN have been performed. Consequently, we suggest the trustworthy hypothesis of tumor-associated heterotopic bone formation through this case. When osteoblastic markers such as BMP9, osteocalcin, and osteopontin are overexpressed in tumor cells, osteoblast-like transformation of such tumor cells occurs. In turn, these tumor cells increase secretion of interactive osteogenetic factors, such as BMP9, osteocalcin, and osteopontin, thus contributing to heterotopic bone formation through a microenvironmental change to mesenchymal stromal cells (osteoblastic differentiation). This phenomenon is considered a type of EMT. Patients should be followed closely because EMT-like transformed tumors have shown a tendency toward local recurrence. Our findings provide insight into the pathogenetic etiology of the heterotopic ossification in LAMN (pseudomyxoma peritonei).