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The prediction of response to treatment would be valuable for managing cervical carcinoma with neoadjuvant chemotherapy.~Background~Background~To this end, the expression of VEGF was analyzed by immunohistochemistry using paraffin-embedded pre-treatment cervical biopsy tissues. This study included 29 patients with bulky IB to IIA cervical squamous cell carcinoma treated with neoadjuvant chemotherapy.~Methods~Methods~Fifteen (51.7%) of 29 patients were scored as VEGF-positive. Response to chemotherapy (complete response or residual tumor with less than 3 mm stromal invasion) was observed in eight patients (27.6%), and it was negatively associated with VEGF expression (P = 0.009). With logistic regression analysis, VEGF positivity continued to be an independent predictor for poor response (P = 0.032). In addition, the progression-free survival rate was significantly lower in patients with VEGF-positive tumors (P = 0.033).~Results~Results~Pretreatment assessment of VEGF expression may provide additional information for identification of patients with cervical cancer who had a low likelihood of response to neoadjuvant chemotherapy and an unfavorable prognosis.~Conclusion~Conclusions [ABSTRACT FROM AUTHOR]

Background: No standard treatment guidelines have been established for postpartum hemorrhage (PPH). We aimed to assess the differences in outcomes and prognoses between patients with PPH who underwent surgical and non-surgical treatment., Methods: This retrospective study included 230 patients diagnosed with PPH at two referral hospitals between August 2013 and October 2023. The patients were divided into non-surgical (group 1, n = 159) and surgical intervention groups (group 2, n = 71). A subgroup analysis was performed by dividing the surgical intervention group into immediate (n = 45) and delayed surgical intervention groups (n = 26)., Results: Initial lactic acid levels and shock index were significantly higher in group 2 (2.85 ± 1.37 vs. 4.54 ± 3.63 mmol/L, p = 0.001, and 0.83 ± 0.26 vs. 1.10 ± 0.51, p < 0.001, respectively). Conversely, initial heart rate and body temperature were significantly lower in group 2 (92.5 ± 21.0 vs. 109.0 ± 28.1 beat/min, p < 0.001, and 37.3 ± 0.8 °C vs. 37.0 ± 0.9 °C, p = 0.011, respectively). Logistic regression analysis identified low initial body temperature, high lactic acid level, and shock index as independent predictors of surgical intervention (p = 0.029, p = 0.027, and p = 0.049, respectively). Regarding the causes of PPH, tone was significantly more prevalent in group 1 (57.2% vs. 35.2%, p = 0.002), whereas trauma was significantly more prevalent in group 2 (24.5% vs. 39.4%, p = 0.030). Group 2 had worse overall outcomes and prognoses than group 1. The subgroup analysis showed significantly higher rates of uterine atony combined with other causes, hysterectomy, and disseminated intravascular coagulopathy in the delayed surgical intervention group than the immediate surgical intervention group (42.2% vs. 69.2%, p = 0.027; 51.1% vs. 73.1%, p = 0.049; and 17.8% vs. 46.2%, p = 0.018, respectively)., Conclusions: Patients with PPH presenting with increased lactic acid levels and shock index and decreased body temperature may be surgical candidates. Additionally, immediate surgical intervention in patients with uterine atony combined with other causes of PPH could improve prognosis and reduce postoperative complications., (© 2024. The Author(s).)

Background: This study aimed to identify plasma and urinary cytokines as potential biomarkers for severe knee osteoarthritis (OA). It also investigated associations between these cytokines and cartilage markers, as well as their connections with synovial fluid (SF) markers., Methods: Samples of plasma, urine, and SF were obtained from patients (n = 40) undergoing total knee arthroplasty (TKA) or unicompartmental knee arthroplasty (UKA) due to severe knee OA. Control samples of plasma and urine were collected from non-OA individuals (n = 15). We used a Luminex immunoassay for the simultaneous measurement of 19 cytokines, MMP-1, and MMP-3 levels. COMP, CTX-II, and hyaluronan (HA) levels were quantified using enzyme-linked immunosorbent assay (ELISA) kits. Receiver operating characteristic (ROC) curves were utilized to analyze each biomarker's performance. Correlations among these biomarkers were evaluated via Spearman's correlation., Results: The levels of plasma (p)CCL11, pCXCL16, pIL-8, pIL-15, pHA, urinary (u)CCL2, uCCL11, uCCL19, uCXCL16, uIL-1β, uIL-6, uIL-8, uIL-12p70, uIL-15, uIL-33, uMMP-3, uHA, uCTX-II, and uCOMP were significantly elevated in individuals with severe knee OA. Notably, specific correlations were observed between the plasma/urine biomarkers and SF biomarkers: pCCL11 with sfHA (r = 0.56) and sfTNF-α (r = 0.58), pIL-15 with sfCCL19 (r = 0.43) and sfCCL20 (r = 0.44), and uCCL19 with sfCCL11 (r = 0.45) and sfIL-33 (r = 0.51). Positive correlations were also observed between uCCL11 and its corresponding sfCCL11(r = 0.49), as well as between sfCCL11 and other cytokines, namely sfCCL4, sfCCL19, sfCCL20, sfIL-33, and sfTNF-α (r = 0.46-0.63)., Conclusion: This study provides an extensive profile of systemic inflammatory mediators in plasma of knee OA and identified four inflammatory markers (pCCL11, pIL-15, uCCL11, and uCCL19) reflecting joint inflammation., (© 2024. The Author(s).)

Background: Biliary tract cancer (BTC) is a relatively rare but aggressive gastrointestinal cancer with a high mortality rate. Cancer stem cell (CSC) populations play crucial roles in tumor biology and are responsible for the low response to anti-cancer treatment and the high recurrence rate. This study investigated the role of Transgelin-2 (TAGLN2), overexpressed in CSC in BTC cells, and analyzed its expression in patient tissues and serum to identify potential new targets for BTC., Methods: TAGLN2 expression was suppressed by small-interfering or short hairpin RNAs, and its effects on tumor biology were assessed in several BTC cell lines. Furthermore, the effects of TAGLN2 silencing on gemcitabine-resistant BTC cells, differentially expressed genes, proteins, and sensitivity to therapeutics or radiation were assessed. TAGLN2 expression was also assessed using western blotting and immunohistochemistry in samples obtained from patients with BTC to validate its clinical application., Results: Suppression of TAGLN2 in BTC cell lines decreased cell proliferation, migration, invasion, and tumor size, in addition to a reduction in CSC features, including clonogenicity, radioresistance, and chemoresistance. TAGLN2 was highly expressed in BTC tissues, especially in cancer-associated fibroblasts in the stroma. Patients with a low stromal immunohistochemical index had prolonged disease-free survival compared to those with a high stromal immunohistochemical index (11.5 vs. 7.4 months, P = 0.013). TAGLN2 expression was higher in the plasma of patients with BTC than that in those with benign diseases. TAGLN2 had a higher area under the curve (0.901) than CA19-9, a validated tumor biomarker (0.799; P < 0.001)., Conclusion: TAGLN2 plays a critical role in promoting BTC cell growth and motility and is involved in regulating BTC stemness. Silencing TAGLN2 expression enhanced cell sensitivity to radiation and chemotherapeutic drugs. The expression of TAGLN2 in patient tissue and plasma suggests its potential to serve as a secretory biomarker for BTC. Overall, targeting TAGLN2 could be an appropriate therapeutic strategy against advanced cancer following chemotherapy failure., (© 2024. The Author(s).)

Background: Recent studies using single-cell transcriptomic analysis have reported several distinct clusters of neoplastic epithelial cells and cancer-associated fibroblasts in the pancreatic cancer tumor microenvironment. However, their molecular characteristics and biological significance have not been clearly elucidated due to intra- and inter-tumoral heterogeneity., Methods: We performed single-cell RNA sequencing using enriched non-immune cell populations from 17 pancreatic tumor tissues (16 pancreatic cancer and one high-grade dysplasia) and generated paired spatial transcriptomic data from seven patient samples., Results: We identified five distinct functional subclusters of pancreatic cancer cells and six distinct cancer-associated fibroblast subclusters. We deeply profiled their characteristics, and we found that these subclusters successfully deconvoluted most of the features suggested in bulk transcriptome analysis of pancreatic cancer. Among those subclusters, we identified a novel cancer cell subcluster, Ep&#95;VGLL1, showing intermediate characteristics between the extremities of basal-like and classical dichotomy, despite its prognostic value. Molecular features of Ep&#95;VGLL1 suggest its transitional properties between basal-like and classical subtypes, which is supported by spatial transcriptomic data., Conclusions: This integrative analysis not only provides a comprehensive landscape of pancreatic cancer and fibroblast population, but also suggests a novel insight to the dynamic states of pancreatic cancer cells and unveils potential therapeutic targets., (© 2024. The Author(s).)

Background: The B7-H3 protein, encoded by the CD276 gene, is a member of the B7 family of proteins and a transmembrane glycoprotein. It is highly expressed in various solid tumors, such as lung and breast cancer, and has been associated with limited expression in normal tissues and poor clinical outcomes across different malignancies. Additionally, B7-H3 plays a crucial role in anticancer immune responses. Antibody-drug conjugates (ADCs) are a promising therapeutic modality, utilizing antibodies targeting tumor antigens to selectively and effectively deliver potent cytotoxic agents to tumors., Methods: In this study, we demonstrate the potential of a novel B7-H3-targeting ADC, ITC-6102RO, for B7-H3-targeted therapy. ITC-6102RO was developed and conjugated with dHBD, a soluble derivative of pyrrolobenzodiazepine (PBD), using Ortho Hydroxy-Protected Aryl Sulfate (OHPAS) linkers with high biostability. We assessed the cytotoxicity and internalization of ITC-6102RO in B7-H3 overexpressing cell lines in vitro and evaluated its anticancer efficacy and mode of action in B7-H3 overexpressing cell-derived and patient-derived xenograft models in vivo., Results: ITC-6102RO inhibited cell viability in B7-H3-positive lung and breast cancer cell lines, inducing cell cycle arrest in the S phase, DNA damage, and apoptosis in vitro. The binding activity and selectivity of ITC-6102RO with B7-H3 were comparable to those of the unconjugated anti-B7-H3 antibody. Furthermore, ITC-6102RO proved effective in B7-H3-positive JIMT-1 subcutaneously xenografted mice and exhibited a potent antitumor effect on B7-H3-positive lung cancer patient-derived xenograft (PDX) models. The mode of action, including S phase arrest and DNA damage induced by dHBD, was confirmed in JIMT-1 tumor tissues., Conclusions: Our preclinical data indicate that ITC-6102RO is a promising therapeutic agent for B7-H3-targeted therapy. Moreover, we anticipate that OHPAS linkers will serve as a valuable platform for developing novel ADCs targeting a wide range of targets., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: It is proposed that the development of parenteral nutrition-associated cholestasis (PNAC) was significantly associated with preterm birth, low birth weight, infection, etc.; however, the etiology and pathogenesis of PNAC are not fully understood. Most of the studies examining PNAC-associated risk factors were single-center studies with relatively small sample sizes., Objective: To analyze the risk factors associated with PNAC in preterm infants in China., Methods: This is a retrospective multicenter observational study. Clinical data on the effect of multiple oil-fat emulsions (soybean oil-medium chain triglycerides-olive oil-fish oil, SMOF) in preterm infants were collected from a prospective multicenter randomized controlled study. A secondary analysis was performed in which preterm infants were divided into the PNAC group and the non-PNAC group based on the PNAC status., Results: A total of 465 cases very preterm infants or very low birth weight infants were included in the study in which 81 cases were assigned to the PNAC group and 384 cases were assigned to the non-PNAC group. The PNAC group had a lower mean gestational age, lower mean birth weight, longer duration of invasive and non-invasive mechanical ventilation, a longer duration oxygen support, and longer hospital stay (P < 0.001 for all). The PNAC group had higher respiratory distress syndrome, hemodynamically significant patent ductus arteriosus, necrotizing enterocolitis (NEC) with stage II or higher, surgically treated NEC, late-onset sepsis, metabolic bone disease, and extrauterine growth retardation (EUGR) compared to the non-PNAC group (P < 0.05 for all). In contrast with the non-PNAC group, the PNAC group received a higher maximum dose of amino acids and fat emulsion, more medium/long-chain fatty emulsion, less SMOF, had a longer duration of parenteral nutrition, lower rates of breastfeeding, higher incidence of feeding intolerance (FI), more accumulated days to achieve total enteral nutrition, less accumulated days of total calories up to standard 110 kcal/kg/day and slower velocity of weight growth (P < 0.05 for all). Logistic regression analysis indicated that the maximum dose of amino acids (OR, 5.352; 95% CI, 2.355 to 12.161), EUGR (OR, 2.396; 95% CI, 1.255 to 4.572), FI (OR, 2.581; 95% CI, 1.395 to 4.775), surgically treated NEC (OR, 11.300; 95% CI, 2.127 ~ 60.035), and longer total hospital stay (OR, 1.030; 95% CI, 1.014 to 1.046) were independent risk factors for the development of PNAC. SMOF (OR, 0.358; 95% CI, 0.193 to 0.663) and breastfeeding (OR, 0.297; 95% CI, 0.157 to 0.559) were protective factors for PNAC., Conclusions: PNAC can be reduced by optimizing the management of enteral and parenteral nutrition and reducing gastrointestinal comorbidities in preterm infants., (© 2023. The Author(s).)

Background: Traumatic tracheal injury is a rare type of trauma. In this type of injury, catastrophes may occur owing to a failure to secure the patient's airway. Extracorporeal membrane oxygenation (ECMO) is rescue therapy available for the treatment of urgent cardiorespiratory distress until the patient's vital signs have stabilized. The various applications of ECMO configurations have expanded the scope for this therapy., Case Presentation: We describe the case of a 66-year-old man with tracheal rupture with thyroid cartilage fracture due to cultivator handle who was treated with veno-venous ECMO. This case reflects the role and limitations of veno-venous ECMO, in which patient survival was possible with a bi-femoral configuration while also ensuring a clear airway., Conclusion: We shared our experience with bi-femoral veno-venous ECMO as a therapeutic option to contribute to choosing an appropriate approach. Based on our review of the literature, the present case was an uncommon report of survival after tracheal rupture due to trauma without other complications., (© 2022. The Author(s).)

Background: It is unclear whether different anterior cruciate ligament (ACL) graft trajectories in the distal femur would have different effects on stress generated within the distal femur around the femoral tunnel during knee motion. Thus, the purpose of this study was to determine differences in stress patterns around the femoral tunnel created by trans-portal (TP) vs. modified trans-tibial (TT) technique in anatomical ACL reconstruction at different knee flexion angles., Methods: Twelve male subjects' right knees were scanned with a high-resolution computed tomography (CT) scanner (slice thickness: 1 mm) at four different knee flexion angles (0°, 45°, 90°, and 135°). Three-dimensional (3D) models of these four different flexion angles were created and manipulated with several modelling programs. For the TP group, the virtual femoral tunnelling procedure was performed in a 135° flexion model from the low far anteromedial (AM) portal. For the modified TT group, the same knee models were drilled through the modified TT technique at 90° of flexion separately. Virtual grafts under tension of 40 N were put into corresponding bone tunnel and fixed at the outer aperture of femoral tunnels to simulate the suspensory fixation, followed by fixation of the grafts at the middle of tibial tunnels in the 0° knee flexion models. Finally, the models were exported to a finite element analysis package and analysed using ABAQUS/Explicit code (ABAQUS, USA) to monitor the stress occurring at the node where stress distribution occurred most significantly in the femoral bone around the bone tunnel., Results: In general, both groups showed a high stress distribution in bony structures around inner and outer orifices of the femoral tunnel. Mean maximal stresses occurring at the lateral femoral condyle around the inner orifice of the femoral tunnel in the TP group were found to be significantly greater than those in the modified TT group at all flexion angles except 90° of flexion. Mean maximal stresses monitored around the outer orifice of the femoral tunnel in the TP group were also significantly greater than those in the modified TT group at all flexion angles., Conclusions: Different tunnelling technologies could yield different stress patterns in the lateral femoral condyle around the femoral tunnel. During knee motion, higher stresses were noticed in the TP group than in the modified TT group, especially around inner and outer orifices of the tunnel. Position of the tunnel after reconstruction with the TP technique can have a greater effect on the stress increase in the femur compared to that with the modified TT technique., (© 2022. The Author(s).)

Background: We evaluated the accuracy of the prehospital Field Triage Decision Scheme, which has recently been applied in the Korean trauma system, and the factors associated with severe injury and prognosis at a regional trauma center in Korea., Methods: From 2016 to 2018, prehospital data of injured patients were obtained from the emergency medical services of the national fire agency and matched with trauma outcomes at our institution. Severe injury (Injury Severity Score > 15), overtriage/undertriage rate, positive predictive value, negative predictive value, and accuracy were reviewed according to the triage protocol steps. A multivariate logistic regression analysis was performed to identify influencing factors in the field triage., Results: Of the 2438 patients reviewed, 853 (35.0%) were severely injured. The protocol accuracy was as follows: step 1, 72.3%; step 2, 65.0%; step 3, 66.2%; step 1 or 2, 70.2%; and step 1, 2, or 3, 66.4%. Odds ratios (OR) (95% confidence interval [CIfor systolic blood pressure < 90 mmHg (3.535 [1.920-6.509]; p < 0.001), altered mental status (17.924 [8.980-35.777]; p < 0.001), and pedestrian injuries (2.473 [1.339-4.570], p = 0.04) were significantly associated with 24-h mortality. Penetrating torso injuries (7.108 [4.108-12.300]; p < 0.001); two or more proximal long bone fractures (4.134 [2.316-7.377]); p < 0.001); crushed, degloved, and mangled extremities (8.477 [4.068-17.663]; p < 0.001); amputation proximal to the wrist or ankle (42.964 [5.764-320.278]; p < 0.001); and fall from height (2.141 [1.497-3.062]; p < 0.001) were associated with 24-h surgical intervention., Conclusion: The Korean field triage protocol is not yet accurate, with only some factors reflecting injury severity, making reevaluation necessary., (© 2022. The Author(s).)

Background: Subclavian artery aneurysms are rare but may cause life-threatening complications. Surgical repair has been performed as a treatment of choice, but recently, with the development of endovascular treatment, many endovascular repairs have been performed to prevent surgical complications., Case Presentation: A patient undergoing endovascular repair with a subclavian artery aneurysm was diagnosed with a type II endoleak with an enlarged aneurysmal sac. Surgical repair was performed to remove the aneurysmal sac compressing the adjacent organs., Conclusions: The highly mobile subclavian artery has abundant collaterals. Therefore, regular follow-up is essential for endovascular repair. Surgical repair is effective when adjacent organs are compressed by the aneurysm sac., (© 2022. The Author(s).)

Background: Immunotherapy has been administered to many patients with non-small-cell lung cancer (NSCLC). However, only few studies have examined toxicity in patients receiving an immune checkpoint inhibitor (ICI) after concurrent chemoradiotherapy (CCRT). Therefore, we performed a retrospective study to determine factors that predict radiation pneumonitis (RP) in these patients., Methods: We evaluated the size of the planning target volume, mean lung dose (MLD), and the lung volume receiving more than a threshold radiation dose (VD) in 106 patients. The primary endpoint was RP ≥ grade 2, and toxicity was evaluated., Results: After CCRT, 51/106 patients were treated with ICI. The median follow-up period was 11.5 months (range, 3.0-28.2), and RP ≥ grade 2 occurred in 47 (44.3%) patients: 27 and 20 in the ICI and non-ICI groups, respectively. Among the clinical factors, only the use of ICI was associated with RP (p = 0.043). Four dosimetric variables (MLD, V20, V30, and V40) had prognostic significance in univariate analysis for occurrence of pneumonitis (hazard ratio, p-value; MLD: 2.3, 0.009; V20: 2.9, 0.007; V30: 2.3, 0.004; V40: 2.5, 0.001). Only V20 was a significant risk factor in the non-ICI group, and MLD, V30, and V40 were significant risk factors in the ICI group. The survival and local control rates were superior in the ICI group than in the non-ICI group, but no significance was observed., Conclusions: Patients receiving ICI after definitive CCRT were more likely to develop RP, which may be related to the lung volume receiving high-dose radiation. Therefore, several factors should be carefully considered for patients with NSCLC., (© 2021. The Author(s).)

Background: Cancer stem cells (CSCs) are implicated in carcinogenesis, cancer progression, and recurrence. Several biomarkers have been described for pancreatic ductal adenocarcinoma (PDAC) CSCs; however, their function and mechanism remain unclear., Method: In this study, secretome analysis was performed in pancreatic CSC-enriched spheres and control adherent cells for biomarker discovery. Glutaredoxin3 (GLRX3), a novel candidate upregulated in spheres, was evaluated for its function and clinical implication., Results: PDAC CSC populations, cell lines, patient tissues, and blood samples demonstrated GLRX3 overexpression. In contrast, GLRX3 silencing decreased the in vitro proliferation, migration, clonogenicity, and sphere formation of cells. GLRX3 knockdown also reduced tumor formation and growth in vivo. GLRX3 was found to regulate Met/PI3K/AKT signaling and stemness-related molecules. ELISA results indicated GLRX3 overexpression in the serum of patients with PDAC compared to that in healthy controls. The sensitivity and specificity of GLRX3 for PDAC diagnosis were 80.0 and 100%, respectively. When GLRX3 and CA19-9 were combined, sensitivity was significantly increased to 98.3% compared to that with GLRX3 or CA19-9 alone. High GLRX3 expression was also associated with poor disease-free survival in patients receiving curative surgery., Conclusion: Overall, these results indicate GLRX3 as a novel diagnostic marker and therapeutic target for PDAC targeting CSCs., (© 2021. The Author(s).)

Background: Antiphospholipid syndrome (APS) is associated with a high incidence of thrombotic events, either arterial thrombosis or venous thrombosis. However, APS-related non-thrombotic venous stenosis is rarely reported., Case Presentation: This study described two cases of young women with APS-related internal jugular vein stenosis (IJVS) and reviewed current literature on this issue, including clinical features, diagnosis, and treatment., Conclusions: IJVS is a rather rare complication of APS. Two cases were reported for the first time that high titer of antiphospholipid antibodies (aPL) might mediate direct vessel wall damage and further induce venous stenosis despite long-term standardized anticoagulation to prevent thrombus formation. Therefore, dynamic monitoring of autoantibodies and concomitant use of anticoagulants and corticosteroids may be necessary to the management of APS and its complications.

Background: There has been no gold standard of the initial treatment strategy for acute patellar dislocation (APD) with osteochondral fracture (OCF). Hence the study aim is firstly, to review and compare clinical outcomes of patients who underwent conservative treatment for APD with or without OCF. Secondly, to characterize the location and size of fracture fragment., Methods: Sixty-nine consecutive patients who were retrospectively evaluated after first-time APD over a 2- year period were divided into two groups (group 1 (n = 24): APD with OCF and group 2 (n = 45): APD only). Magnetic resonance imaging (MRI) was used to assess patients with APD and OCF from the medial patella. All patients were treated with a supervised course of immobilization followed by progressive range of motion and strength exercise protocol. History of a recurrent dislocation, radiologic and functional scores were analyzed., Results: Redislocation rate was 31.2% in group 1 and 26.6% in group 2, showing no significant difference between the two groups (p = 0.690). Intergroup differences in terms of final Kujala and IKDC scores were not significant (p = 0.117 and p = 0.283, respectively). Fracture sites of the patella in group 1 were classified as follows: patellar medial margin (12), inferomedial facet (7), and inferomedial facet involving central ridge (5). In the subgroup of patient with OCF of the inferomedial facet of the patella, the fragments were found in the lateral gutter and did not cause pain or mechanical symptoms. Thus, loose body removal was not performed. However, all five patients with large OCF involving the central ridge of the patella failed non-operative treatment with recurrent dislocations, ultimately requiring fragment refixation and medial retinacular imbrication., Conclusions: First, APD patients with OCFs of medial margin or inferomedial facet showed similar redislocation rates and functional knee scores with those without OCFs after conservative treatment. Second, initial conservative treatment failed in some APD patients with large OCF, especially when OCFs were fractured from inferomedial facet involving central ridge. Surgery should be considered with this type.

Background: The use of fluoroscopically-guided interventional (FGI) procedures by orthopedic surgeons has been increasing. This study aimed to investigate the occupational radiation exposure among orthopedic surgeons in South Korea., Methods: A nationwide survey of orthopedic surgeons was conducted in South Korea in October 2017. The dosimetry data of the participants were obtained from the National Dosimetry Registry. The orthopedic surgeons were categorized by job specialty [spine or trauma specialists, other orthopedic specialists, and residents], and descriptive statistics for the demographics and work-related characteristics were presented. Multivariable logistic regression analysis was used to evaluate the risk factors for the orthopedic surgeons who were not linked with the dosimetry data., Results: Among the total participants ( n  = 513), 40.5% of the orthopedic surgeons spent more than 50% of their time working with the FGI procedures when compared with their overall work. The average frequency of the FGI procedures among the orthopedic surgeons was 12.3 days per month. Less than 30% of the participants were regularly provided with radiation monitoring badges. The proportion of subjects who always wore lead aprons and thyroid shields were 52 and 29%, respectively. The residents group experienced more unfavorable working conditions of radiation exposure than the other specialists. The dosimetry data were not significantly linked among the residents (odds ratio [OR] 2.10, 95% confidence interval [CI] 1.11-3.95) and orthopedic surgeons working at small hospitals (OR 4.76, 95% CI 1.05-21.51)., Conclusions: Although orthopedic surgeons often performed FGI procedures, they wore protective gear less frequently, and a large proportion of orthopedic surgeons were not monitored by the national radiation dosimetry system. As the number of radiation procedures performed by the orthopedic surgeons increases, more intensive approaches are needed to reduce radiation exposure, especially for spine and trauma surgeons., Competing Interests: Competing interestsThe authors declare that they have no competing interests., (© The Author(s) 2020.)

Background: The mitotic count in breast carcinoma is an important prognostic marker. Unfortunately substantial inter- and intra-laboratory variation exists when pathologists manually count mitotic figures. Artificial intelligence (AI) coupled with whole slide imaging offers a potential solution to this problem. The aim of this study was to accordingly critique an AI tool developed to quantify mitotic figures in whole slide images of invasive breast ductal carcinoma., Methods: A representative H&E slide from 320 breast invasive ductal carcinoma cases was scanned at 40x magnification. Ten expert pathologists from two academic medical centers labeled mitotic figures in whole slide images to train and validate an AI algorithm to detect and count mitoses. Thereafter, 24 readers of varying expertise were asked to count mitotic figures with and without AI support in 140 high-power fields derived from a separate dataset. Their accuracy and efficiency of performing these tasks were calculated and statistical comparisons performed., Results: For each experience level the accuracy, precision and sensitivity of counting mitoses by users improved with AI support. There were 21 readers (87.5%) that identified more mitoses using AI support and 13 reviewers (54.2%) that decreased the quantity of falsely flagged mitoses with AI. More time was spent on this task for most participants when not provided with AI support. AI assistance resulted in an overall time savings of 27.8%., Conclusions: This study demonstrates that pathology end-users were more accurate and efficient at quantifying mitotic figures in digital images of invasive breast carcinoma with the aid of AI. Higher inter-pathologist agreement with AI assistance suggests that such algorithms can also help standardize practice. Not surprisingly, there is much enthusiasm in pathology regarding the prospect of using AI in routine practice to perform mundane tasks such as counting mitoses.

Background: Systemic inflammation plays a critical role in cancer progression and oncologic outcomes in cancer patients. We investigated whether preoperative inflammatory biomarkers, including C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and neutrophil to lymphocyte ratio (NLR), could be surrogate biomarkers for predicting overall survival (OS) in soft tissue sarcoma (STS) patients treated with surgery and postoperative radiotherapy., Methods: A series of 99 patients who presented with localized extremity STS were retrospectively reviewed. The preoperative CRP levels, ESR, and NLR were evaluated for associations with OS, disease-free survival (DFS), local recurrence-free survival (LRFS), and distant metastasis-free survival (DMFS). Cutoff values for CRP, ESR, and NLR were derived from receiver-operating characteristic curve analysis., Results: Elevated CRP (> 0.14 mg/dL), ESR (> 15 mm/h), and NLR (> 1.95) levels were seen in 33, 44, and 45 patients, respectively. Of these three inflammatory biomarkers, elevated CRP and ESR were associated with a poorer OS (CRP: P = 0.050; ESR: P = 0.001), DFS (CRP: P = 0.023; ESR: P = 0.003), and DMFS (CRP: P = 0.015; ESR: P = 0.001). By multivariate analysis, an elevated ESR was found to be an independent prognostic factor for OS (HR 3.580, P = 0.025) and DMFS (HR 3.850, P = 0.036) after adjustment for other established prognostic factors., Conclusions: The preoperative ESR level is a simple and useful surrogate biomarker for predicting survival outcomes in STS patients and might improve the identification of high-risk patients of tumor relapse in clinical practice.

Background: Pancreatic and biliary tract cancer (PC and BTC, respectively) are difficult to diagnose because of their clinical characteristics; however, recent studies suggest that serum microRNAs (miRNAs) might be the key to developing more efficient diagnostic methods for these cancers., Methods: We analysed the genome-wide expression of serum miRNAs in PC and BTC patients to identify novel biomarker candidates using high-throughput sequencing and experimentally validated miRNAs on clinical samples., Results: Statistical and classification analysis of the serum miRNA-expression profiles of 55 patient samples showed distinguishable patterns between cancer patients and healthy controls; however, we were unable to distinguish the two cancers. We found that three of the highest performing miRNAs were capable of distinguishing cancer patients from controls, with an accuracy of 92.7%. Additionally, dysregulation of these three cancer-specific miRNAs was demonstrated in an independent sample group by quantitative reverse transcription polymerase chain reaction., Conclusions: These results suggested three candidate serum miRNAs (mir-744-5p, mir-409-3p, and mir-128-3p) as potential biomarkers for PC and BTC diagnosis.

Restoration of neutral mechanical alignment of the lower limb is an important factor in the treatment of unicompartmental arthrosis. Traditionally, medial opening wedge high tibial osteotomy has been widely performed to correct varus malalignment with unicompartmental arthrosis. However, an ideal indication for the high tibial osteotomy is the knee with metaphyseal tibial varus malalignment. The basic principle of corrective osteotomy is performing an osteotomy at the center of the deformity to prevent abnormal joint line obliquity. If pathologic distal femoral varus deformity is the cause of genu varum, the osteotomy should be performed in the distal femur. Reports of medial opening wedge distal femoral osteotomy (DFO) to correct varus malalignment are rare. We present a case of this very rare and challenging condition in a 47-year-old male, which was successfully treated by medial opening wedge DFO.

Background: Combined stereotactic body radiotherapy (SBRT) for lung lesions and conventional radiotherapy (CRT) for nodal areas may be more effective than CRT alone in patients with locally advanced lung cancer., Methods: This study included 21 patients with small primary lung tumors distant from the regional nodal areas. The SBRT dose was 40-60 Gy in 4 fractions. CRT doses were 66 Gy in 30 fractions for non-small cell lung cancer and 52.5 Gy in 25 fractions for small cell lung cancer., Results: The median follow-up duration was 12 months, and the median survival was 13 months. The 1 year overall survival, local recurrence-free survival, and distant metastasis-free survival rates were 60.5, 84.8, and 62.1%, respectively. Two patients experienced in-field local recurrence combined with out-field regional recurrence and/or distant failure. The major recurrence pattern was distant failure (crude incidence, 43%). Three patients aged ≥79 years experienced grade ≥ 3 acute radiation pneumonitis, and one also had idiopathic interstitial pneumonia., Conclusion: The combination of SBRT for the lung lesion and CRT for the nodal region seems to be effective and safe for lung malignancies. However, patients older in age and/or with underlying pulmonary disease require stricter lung dose constraints.

Background: To evaluate the role of radiotherapy (RT) as an adjuvant or definitive treatment in primary tracheal adenoid cystic carcinoma (ACC) for local tumor control and survival., Methods: A retrospective chart review was performed in 22 patients treated with adjuvant or definitive RT for primary tracheal ACC at a single center between November 1994 and December 2008., Results: Thirteen and 9 patients received adjuvant and definitive RT, respectively. Microscopic residual disease after surgery was pathologically reported in 11 patients. The median RT dose was 59.4 Gy for adjuvant and 74.4 Gy for definitive RT. The overall response rate for definitive RT was 77.8%. Six patients in the definitive RT group exhibited local progression (LP), whereas 14 patients in both groups exhibited distant metastasis. The most common recurrence site in cases of treatment failure was the lung parenchyma. The median follow-up duration was 123 months, and the 10-year overall survival (OS) rate was 54.2%. Although LP was the most common cause of death (4 patients), two-thirds of the patients treated with definitive RT lived for >5 years. The 5-year and 10-year LP-free survival (LPFS) rates in the definitive RT group were 66.7 and 26.7%, respectively. Patients with higher RT dose by brachytherapy boost had good 5-year OS, 83.3%, and showed no local progression till 5-years. Most of the RT-induced side-effects were mild and tolerable, but 2 patients died of tracheal stenosis without any tumor recurrence., Conclusions: Adjuvant RT may be suitable for controlling microscopic residual disease, whereas definitive RT may yield appropriate long-term survival in >50% patients with unresectable tracheal ACC. Dose escalation should be considered to warrant long-term survival in definitive RT.

Background: Emergence delirium is a behavioral disturbance after general anesthesia in children and may distress both the patients and the primary caregivers, such as parents and medical staff, looking after the patients. Various medical and emotional interventions have been investigated to reduce emergence delirium; however, none are completely effective. This trial intends to assess whether the mother's recorded voice can reduce this adverse post-anesthesia event and facilitate arousal from general anesthesia., Methods/design: This is a prospective, double-blind, single-center, parallel-arm, superiority, randomized controlled trial to be conducted in participants aged 2-8 years who are undergoing elective surgery requiring general anesthesia. Participants will be randomly assigned to one of two groups: those who are stimulated to wake up by listening to their mother's recorded voice (maternal group, n = 33) or a stranger's voice (stranger group, n = 33) during anesthetic emergence. The primary outcome is the initial emergence delirium score in the post-anesthesia care unit (PACU). The secondary outcomes are hemodynamic parameters, including heart rate and mean blood pressure, the duration of time between the cessation of anesthetics and a BIS level of 60, 70 and 80, eye-opening or purposeful movement time, extubation time, total consumption of analgesics, PACU stay time, emergence delirium and pain scores during the PACU stay., Discussion: This is the first randomized controlled trial to investigate the effect of a mother's recorded voice during emergence on the pediatric emergence profile after general anesthesia. It may provide prophylactic treatment options to decrease emergence delirium and enhance arousal from general anesthesia., Trial Registration: ClicnicalTrials.gov, ID: NCT02955680 . Registered on 2 November 2016.

Background: Patient-derived xenograft (PDX) models are important tools in precision medicine and for the development of targeted therapies to treat cancer patients. This study aimed to evaluate our precision medicine strategy that integrates genomic profiling and preclinical drug-screening platforms, in order to personalize cancer treatments using PDX models., Methods: We performed array-comparative genomic hybridization, microarray, and targeted next-generation sequencing analyses, in order to determine the oncogenic driver mutations. PDX cells were obtained from PDXs and subsequently screened in vitro with 17 targeted agents., Results: PDX tumors recapitulated the histopathologic and genetic features of the patient tumors. Among the samples from lung cancer patients that were molecularly-profiled, copy number analysis identified unique focal MET amplification in one sample, 033 T, without RTK/RAS/RAF oncogene mutations. Although HER2 amplification in 033 T was not detected in the cancer panel, the selection of HER2-amplified clones was found in PDXs and PDX cells. Additionally, MET and HER2 overexpression were found in patient tumors, PDXs, and PDX cells. Crizotinib or EGFR tyrosine kinase inhibitor treatments significantly inhibited cell growth and impaired tumor sphere formation in 033 T PDX cells., Conclusions: We established PDX cell models using surgical samples from lung cancer patients, and investigated their preclinical and clinical implications for personalized targeted therapy. Additionally, we suggest that MET and EGFR inhibitor-based therapy can be used to treat MET and HER2-overexpressing lung cancers, without receptor tyrosine kinase /RAS/RAF pathway alterations.

Background: Solitary fibrous tumors of the pleura (SFTPs) are relatively rare tumors that originate from mesenchymal cells of submesothelial tissue of the pleura. Most patients with SFTPs are asymptomatic; however, pleuritic chest pain, cough, and dyspnea can develop. If hypoglycemia is associated with a solitary fibrous tumor, it is referred to as the Doege-Potter syndrome., Case Presentation: A 70-year-old man had visited our hospital with a chief complaint of dyspnea, and he was diagnosed as having a solitary fibrous tumor. A few years later, he developed hypoglycemia, and he underwent excision of the mass., Conclusion: Occasionally, SFTPs induce several paraneoplastic events, such as hypertrophic osteoarthropathy. We described here a patient with an SFTP with Doege-Potter syndrome who was successfully treated with complete resection. Although lesions can be histologically benign, they can clinically present with malignant features.

Background: Coronary artery bypass grafting (CABG) with a composite Y-graft made of the left internal thoracic artery (LITA) and another arterial graft has a risk for hypoperfusion. Changes over time in the diameter of the LITA anastomosed to the left anterior descending coronary artery (LAD) are not known., Methods: Data were collected for 71 patients who had undergone coronary angiography (CAG) immediately and at 1 year following off-pump CABG with a composite Y-graft made of the LITA and either the radial artery or the right gastroepiploic artery. These patients were divided into 2 groups depending on the degree of LAD stenosis. Group 1 (n = 28) consisted of patients with complete occlusion of the LAD. Group 2 (n = 43) consisted of patients with <90% stenosis of the LAD. The clinical state and luminal diameter of the LITA on immediate postoperative and postoperative 1-year CAG were compared and analyzed., Results: On the immediate postoperative CAG, mean LITA diameter of Group 1 was larger than that of Group 2 (2.09 ± 0.53 vs. 1.61 ± 0.33 mm, P = 0.01). Mean LITA diameter 1 year following CABG was also larger in Group 1 than in Group 2 (2.49 ± 0.31 vs. 2.10 ± 0.45 mm, P = 0.005). Both groups showed significant increases in the LITA diameters at postoperative 1 year., Conclusions: The LITA used as a composite Y-graft underwent remodeling, resulting in a larger diameter, to supply adequate myocardial blood. The degree of change in luminal diameter varied according to the severity of the LAD stenosis.

Background: Elderly patients with non-small cell lung cancer (NSCLC) are frequently treated with radiation therapy (RT) alone, due to poor performance status or underlying disease. We investigated the effectiveness of RT over 60 Gy administered alone to NSCLC patients who were unfit or rejecting for combination treatment., Methods and Materials: From April 2002 to July 2010, 83 patients with stage II-III NSCLC, aged over 60 years, treated by RT alone with a curative aim were analyzed. Radiation was targeted to the primary tumor and clinically involved lymph nodes. A total dose of 66 Gy in 30 fractions (2.2 Gy/fraction) was delivered once daily (5 fractions weekly). One month after completing RT, initial tumor responses were evaluated., Results: Median age of patients was 73 years (range, 60 - 82 years). The median survival time was 18.6 months (range, 2-135). The actuarial overall survival rates at 2 and 3 years were 39 % and 23 %, and cause-specific survival rate at 2 and 3 years were 57 % and 47 %, respectively. When primary tumor was controlled, the 2- and 3-year CSS were 56 % and 45 %, but 32 % and 23 % in those patients with local failure, respectively (P = 0.017). Additionally, the local control rate was associated with the initial tumor response (P = 0.01). No patient experienced grade 4+ toxicity., Conclusions: For stage II-III NSCLC patients aged over 60 years and unfit or rejecting for combination treatment, RT alone showed promising result. Long-term disease control can be expected if an early tumor response to radiation is achieved, which could result in improved overall survival rates.

Background: Limited data describe the prognosis after stereotactic ablative radiotherapy for lung metastases arising from colorectal cancer. Thus, we evaluated treatment outcomes of stereotactic ablative radiotherapy for those patients., Methods: The study involved patients received stereotactic ablative radiotherapy for one to three lung metastases arising from colorectal cancer at a single institution. A total dose of 40-60 Gy (median, 48 Gy) in three or four fractions was prescribed., Results: A total of 79 metastatic lung lesions from 50 patients who underwent curative resection for their primary colorectal cancer or salvage treatment at a recurrent site were included. The one- and three-year local control rates were 88.7 % and 70.6 %, respectively. The three-year overall survival and progression-free survival rates were 64.0 % and 24.0 %, respectively. Patients with tumor volume ≤1.5 mL had a significantly better overall survival rate than those with tumor volume >1.5 mL (68.0 % vs. 60.0 % at three-year, p = 0.02). Local control was associated with a trend towards better survival (p = 0.06). No pulmonary complications greater than grade 2 were observed., Conclusion: Stereotactic ablative radiotherapy is a competitive treatment modality for the management of lung metastases arising from colorectal cancer.

Background: Benign prostatic hyperplasia (BPH) is one of the common male diseases, which is provoked by dihydrotestosterone (DHT) and androgen signals. Several studies showed that curcumin has various effects of prevention and treatment to diseases. We investigated whether curcumin may repress the development of BPH in male Wistar rats., Methods: Seven weeks male Wistar rats were and divided into 4 groups (normal group, BPH group, finasteride group, curcumin group; n = 8 for each group). In order to induce BPH in rats, rats were castrated and testosterone was injected subcutaneously everyday (s.c., 20 mg/kg). Rats in the curcumin group were treated 50 mg/kg, administered orally for 4 weeks. After 4 weeks, all rats were sacrificed and their prostate and serum were analyzed., Results: Compared to the finasteride group as positive group, the curcumin group showed similarly protective effect on BPH in histopathologic morphology, prostate volume. Results of immunohistochemistry and western-blot showed decreased expressions of VEGF, TGF-ß1, and IGF1 were also decreased in the curcumin group., Conclusions: These results suggested that curcumin inhibited the development of BPH and might a useful herbal treatment or functional food for BPH.

Pulmonary epithelioid hemangioendothelioma (PEH) is a rare vascular tumor of borderline malignancy that originates from endothelial cells. Chest computed tomography (CT) performed during a routine cancer screening revealed multiple small pulmonary nodules in a 50-year-old man who had previously undergone endoscopic submucosal dissection of early gastric cancer. To rule out metastatic nodules, a wedge resection of the left upper lobe was performed and the frozen biopsy reported a benign fibrotic nodule. Using immunohistochemistry, the final pathology was indicated to be PEH, and consecutive surgery for the right-side nodules was planned and performed.

Background: To compare dosimetric parameters of volumetric modulated arc therapy (VMAT) and non-coplanar intensity modulated radiotherapy (IMRT) for nasal cavity and paranasal sinus cancer with regard to the coverage of planning target volume (PTV) and the sparing of organs at risk (OAR)., Methods: Ten patients with nasal cavity or paranasal sinus cancer were re-planned by VMAT (two-arc) plan and non-coplanar IMRT (7-, 11-, and 15-beam) plans. Planning objectives were to deliver 60 Gy in 30 fractions to 95% of PTV, with maximum doses (D(max)) of <50 Gy to the optic nerves, optic chiasm, and brainstem, <40 Gy to the eyes and <10 Gy to the lenses. The target mean dose (D(mean)) to the parotid glands was <25 Gy, and no constraints were applied to the lacrimal glands. Planning was optimized to minimized doses to OAR without compromising coverage of the PTV. VMAT and three non-coplanar IMRT (7-, 11-, and 15-beam) plans were compared using the heterogeneity and conformity indices (HI and CI) of the PTV, D(max) and D(mean) of the OAR, treatment delivery time, and monitor units (MUs)., Results: The HI and CI of VMAT plan were superior to those of the 7-, 11-, and 15-beam non-coplanar IMRT. VMAT and non-coplanar IMRT (7-, 11-, and 15-beam) showed equivalent sparing effects for the optic nerves, optic chiasm, brainstem, and parotid glands. For the eyes and lenses, VMAT achieved equivalent or better sparing effects when compared with the non-coplanar IMRT plans. VMAT showed lower MUs and reduced treatment delivery time when compared with non-coplanar IMRT., Conclusions: In 10 patients with nasal cavity or paranasal sinus cancer, a VMAT plan provided better homogeneity and conformity for PTV than non-coplanar IMRT plans, with a shorter treatment delivery time, while achieving equal or better OAR-sparing effects and using fewer MUs.

Background: Neuroendocrine tumors (NETs) of the esophagus are extremely rare, and few cases have been reported worldwide. Thus, a comprehensive nationwide study is needed to understand the characteristics of and treatment strategy for esophageal NETs., Methods: We collected data on esophageal NET patients from 25 hospitals in Korea from 2002-2012. The incidence, location, clinical symptoms, histopathology, treatment response, and the biochemical, radiologic and endoscopic characteristics of esophageal NETs were surveyed., Results: Among 2,037 NETs arising in different gastrointestinal sites, esophageal NETs were found in 26 cases (1.3%). The mean patient age was 60.12 ± 9.30 years with a 4:1 male predominance. In endoscopic findings, 76.9% (20/26) of NETs were located in the lower third of the esophagus and the mean size was 2.34 ± 1.63 cm. At diagnosis, more than half the patients (15/26, 57.7%) had regional lymph node metastasis or widespread metastasis. Endoscopic resection was conducted in three cases, and in all three of them, lymph node metastasis was not found and tumor size was below 1.0 cm. All tumors were completely removable through endoscopic procedures and there was no recurrence during the follow-up period. Eighteen other patients received an operation, chemotherapy or both. Among them, nine patients (50.0%) expired because of the progression of their cancer or post-operative complications. In Kaplan-Meier survival analysis, only tumor size (more than 2.0 cm) showed prognostic significance (P = 0.045)., Conclusions: Despite the general assumption that gastrointestinal NETs are benign and slow-growing tumors, the prognosis of advanced esophageal NETs is not favorable.

Background: ent-Sauchinone is a polyphenolic compound found in plants belonging to the lignan family. ent-Sauchinone has been shown to modulate the expression of inflammatory factors through the nuclear factor-kappa B (NF-κB) signaling pathway. It is well known that neuroinflammation is associated with amyloidogenesis. Thus, in the present study, we investigated whether ent-Sauchinone could have anti-amyloidogenic effects through the inhibition of NF-κB pathways via its anti-inflammatory property., Methods: To investigate the potential effect of ent-Sauchinone on anti-neuroinflammation and anti-amyloidogenesis in in vitro studies, we used microglial BV-2 cells and cultured astrocytes treated with ent-Sauchinone (1, 5, and 10 μM) for 24 hours. For the detection of anti-neuro-inflammatory responses, reative oxygen species (ROS) and Nitric oxide (NO) generation and inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression were measured with assay kits and western blotting. β-secretase and β-secretase activities and β-amyloid levels were determined for measuring the anti-amyloidogenic effects of ent-Sauchinone by enzyme assay kits. NF-κB and STAT3 signals were detected with electromobility shift assay (EMSA) to study the related signaling pathways. The binding of ent-Sauchinone to STAT3 was evaluated by a pull-down assay and by a docking model using Autodock VINA software (Hoover's Inc., Texas, United states)., Results: ent-Sauchinone (1, 5, and 10 μM) effectively decreased lipopolysaccharide (LPS)-(1 μg/ml) induced inflammatory responses through the reduction of ROS and NO generations and iNOS and COX-2 expressions in cultured astrocytes and microglial BV-2 cells. ent-Sauchinone also inhibited LPS-induced amyloidogenesis through the inhibition of β-secretase and β-secretase activity. NF- κB amyloid and STAT3, critical transcriptional factors regulating not only inflammation but also amyloidogenesis, were also inhibited in a concentration dependent manner by ent-Sauchinone by blocking the phosphorylation of I κB and STAT3 in cultured astrocytes and microglial BV-2 cells. The docking model approach showed that ent-Sauchinone binds to STAT3, and the employment of a STAT3 inhibitor and siRNA reversed ent-Sauchinone-induced inhibition NF-κB activation and Aβ generation., Conclusions: These results indicated that ent-Sauchinone inhibited neuroinflammation and amyloidogenesis through the inhibition of STAT3-mediated NF-κB activity, and thus could be applied in the treatment of neuro-inflammatory diseases, including Alzheimer's disease.

Background: Among a variety of inflammatory mediators, visfatin is a proinflammatory adipocytokine associated with inflammatory reactions in obesity, metabolic syndrome, chronic inflammatory disease, and autoimmune disease. However, the biological role of visfatin in secretion of major mucins in human airway epithelial cells has not been reported. Therefore, this study was conducted in order to investigate the effect and the brief signaling pathway of visfatin on MUC8 and MUC5B expression in human airway epithelial cells., Results: Visfatin significantly induced MUC8 and MUC5B expression. Visfatin significantly activated phosphorylation of p38 MAPK. Treatment with SB203580 (p38 MAPK inhibitor) and knockdown of p38 MAPK by siRNA significantly blocked visfatin-induced MUC8 and MUC5B expression.Visfatin significantly increased ROS formation. Treatment with SB203580 significantly attenuated visfatin-induced ROS formation. Treatment with NAC (ROS scavenger) and DPI (NADPH oxidase inhibitor) significantly attenuated visfatin-induced MUC8 and MUC5B expression. However, treatment with NAC and DPI did not attenuate visfatin-activated phosphorylation of p38 MAPK. Visfatin significantly activated the phosphorylation of NF-κB. Treatment with PDTC (NF-κB inhibitor) significantly attenuated visfatin-induced MUC8 and MUC5B expression., Conclusions: These results suggest that visfatin induces MUC8 and MUC5B expression through p38 MAPK/ROS/NF-κB signaling pathway in human airway epithelial cells.

Background: To investigate the clinical and dose-volumetric parameters that predict the risk of radiation-induced liver disease (RILD) for patients with small, unresectable hepatocellular carcinoma (HCC) treated with stereotactic body radiotherapy (SBRT)., Methods: Between March 2007 and December 2009, 92 patients with HCC treated with SBRT were reviewed for RILD within 3 months of completing treatment. RILD was evaluated according to the Common Terminology Criteria for Adverse Events, version 3.0. A dose of 10-20 Gy (median, 15 Gy) per fraction was given over 3-4 consecutive days for a total dose of 30-60 Gy (median, 45 Gy). The following clinical and dose-volumetric parameters were examined: age, gender, Child-Pugh class, presence of hepatitis B virus, gross tumor volume, normal liver volume, radiation dose, fraction size, mean dose to the normal liver, and normal liver volumes receiving from < 5 Gy to < 60 Gy (in increments of 5 Gy)., Results: Seventeen (18.5%) of the 92 patients developed grade 2 or worse RILD after SBRT (49 patients in grade 1, 11 in grade 2, and 6 in ≥ grade 3). On univariate analysis, Child-Pugh class was identified as a significant clinical parameter, while normal liver volume and normal liver volumes receiving from < 15 Gy to < 60 Gy were the significant dose-volumetric parameters. Upon multivariate analysis, only Child-Pugh class was a significant parameter for predicting grade 2 or worse RILD., Conclusions: The Child-Pugh B cirrhosis was found to have a significantly greater susceptibility to the development of grade 2 or worse RILD after SBRT in patients with small, unresectable HCC. Additional efforts aimed at testing other models to predict the risk of RILD in a large series of HCC patients treated with SBRT are needed.

This study presents a first case of multiple peripheral typical carcinoid tumors associated with sclerosing hemangiomas in the lung. A 52-year-old male presented with incidentally detected multiple pulmonary nodules on a simple chest X-ray during routine health check-up. A computed tomography (CT) scan of the chest showed multiple nodular lesions in the middle and lower lobes of the right lung. These were initially suspected as inflammatory lesions due to miliary tuberculosis. However, possibility of malignancy could not be excluded and right lower lobe lobectomy was performed. Histopathologically, some nodules including two largest nodules were composed of small round to spindle shaped cells with fine chromatin pattern, whereas the rest of the sclerotic nodules were composed of two epithelial cell types- surface cells and round cells. The final diagnosis of this case was multiple peripheral typical carcinoid tumors associated with sclerosing hemangiomas of the lung. For past three years of post-surgery follow up period, no new lesions or changes in the right middle lobe have been identified.

Background: To evaluate the utility of the preoperative PET-CT using deformable image registration (DIR) in the treatment of patients with locally advanced breast cancer and to find appropriate radiotherapy technique for further adequate treatment of axillary nodal area., Methods: Sixty-five breast cancer patients who had level II, III axillary or supraclavicular lymph node metastasis on ¹⁸F-FDG PET-CT and received postoperative radiotherapy after modified radical mastectomy were enrolled. One radiation oncologist contoured normal organs (axillary vessels, clavicular head, coracoids process and humeral head) and involved lymph nodes on PET-CT and simulation CT slices. After contouring, deformable image registration of PET-CT on simulation CT was carried out. To evaluate the performance of the DIR, Dice similarity coefficient (DSC) and Center of mass (COM) were used. We created two plans, one was the historically designed three field plan and the other was the modified plan based on the location of axillary lymph node, and we compared the doses that irradiated the axillary lymph nodes., Results: The DSCs for axillary artery, axillary vein, clavicular head, coracoids process and humeral head were 0.43 ± 0.15, 0.39 ± 0.20, 0.85 ± 0.10, 0.72 ± 0.20 and 0.77 ± 0.20, respectively. The distances between the COMs of axillary artery, axillary vein, clavicular head, coracoids process and humeral head in simulation CT and from PET-CT were 13.0 ±7.1, 20.2 ± 11.2, 4.4 ± 6.3, 3.7 ± 6.7, and 9.5 ± 25.0 mm, respectively. In the historically designed plan, only 57.7% of level II lymph nodes received more than 95% of prescribed dose and the coverage was improved to 70.0% with the modified plan (p < 0.01). For level III lymph nodes, the volumes received more than 95% of prescribed dose were similar in both plans (96.8 % vs 97.9%, p = 0.35)., Conclusion: Deformable image registration of PET-CT on simulation CT was helpful in the identification of the location of the preoperatively involved axillary lymph node. Historically designed three-field plan was not adequate to treat the axillary level II lymph node area. Novel treatment technique based on the location of axillary lymph node from PET-CT using DIR can result in more adequate coverage of nodal area.

Background: Photodynamic therapy employs photosensitive agents such as porphyrins to treat a variety of tumors accessible to light-emitting probes. This approach capitalizes on the selective retention of porphyrins by cancer cells. Cancer cells also have elevated levels of mitochondrial benzodiazepine receptors which bind porphyrins with high affinity., Methods: Cultured cancer cell lines were exposed to porphyrin and porphyrin-like compounds and then irradiated with light. Cytotoxicity of this treatment was measured via clonogenic assays. Mitochondrial benzodiazepine receptor pharmacology was studied using [3H] PK11195 binding to cancer cell homogenates and isolated kidney mitochondrial membranes., Results: We show that therapeutic potencies of porphyrins correlate closely with affinities for mitochondrial benzodiazepine receptors. Sensitivities of tumor cell lines to photodynamic therapy parallel their densities of these receptors., Conclusion: We propose that porphyrin photodynamic therapy is mediated by mitochondrial benzodiazepine receptors.