Yoon Joo Cho

Background: Knee bone age can differ from hand bone age and is more relevant to lower-extremity pediatric conditions. This study developed and validated a quantitative method for estimating skeletal maturity using knee MRI images. Methods: We identified 695 participants aged 18 years or younger without conditions affecting knee anatomy or maturation who underwent knee MRI. Participants were randomly allocated to the modeling (n=417) and validation (n=278) groups. Twenty-six maturation-related parameters were measured on coronal MRI, including the articular and peripheral cartilaginous thicknesses, physeal thicknesses, ossified epiphyseal width, and capping interval. The capping interval was defined as the distance from the medial or lateral metaphyseal end to the nearest ossified epiphysis. Each parameter was normalized to metaphyseal width and assessed by univariable linear regression against log-transformed chronological age. Top-ranked variables were entered into sex-specific multivariable models. Results: The sums of the medial and lateral capping intervals from the femur and tibia were the only parameters with R ² >0.9 in both sexes and were defined as the femoral and tibial capping interval indices (CIIs), respectively. Final models were age=exp(−1.918[femoral CII]−1.797[tibial CII]+2.813) for males and age=exp(−2.056[femoral CII]−2.487[tibial CII]+2.738) for females. In the validation group, estimated knee bone age showed minimal difference from chronological age (0.1±1.1 y, P =0.534) and very strong correlation ( r _s =0.960). Conclusions: Knee bone age estimated from the femoral and tibial CII showed close agreement with chronological age in the independent validation cohort. This study introduces a novel, simple quantitative method that enables estimation of bone age on knee MRI using a minimal number of parameters. Level of Evidence: Level III—diagnostic.

Background: Although radiographs are the first-line imaging modality, differentiating between neoplastic pathologic fractures and nonpathologic fractures on radiographs can sometimes be challenging. In this study, we aimed to develop and evaluate a deep learning model capable of distinguishing neoplastic pathologic fractures from nonpathologic fractures on hip radiographs to enhance diagnostic accuracy. Methods: This retrospective, multicenter study analyzed anteroposterior hip radiographs from patients who visited the emergency department at 4 different institutions. The deep learning model was trained on, and tested using, data from 338 patients at a single institution and externally validated on data from 488 patients across 3 additional institutions. Results: The model achieved an overall accuracy of 0.880, with a sensitivity of 0.882 and a specificity of 0.879, on the internal test set. It was then externally validated using the data of 488 patients (67 with neoplastic pathologic fracture and 421 with nonpathologic fracture) from institutions separate from where the model was developed. The model achieved an overall accuracy of 0.848, sensitivity of 0.910, and specificity of 0.786. Its performance was comparable with that of general orthopaedic surgeons. Conclusions: The developed deep learning model is a reliable and valid tool for distinguishing neoplastic pathologic fractures from nonpathologic fractures on hip radiographs. It has the potential to assist orthopaedic surgeons in resource-limited settings, where optimizing the interpretation of radiographs is critical for patient care. The model is publicly available at https://pathfxdx.org. Level of Evidence: Diagnostic Level III . See Instructions for Authors for a complete description of levels of evidence.

Background: In most patients, a soft tissue sarcoma is sporadic and not related to a specific known cause; however, demographic, environmental, and lifestyle factors may be linked to its development. Alcohol consumption, a major risk factor for oncogenesis, has increased, particularly among females, and it might be a risk factor for soft tissue sarcoma, with potential differences in the association based on the biological differences between males and females. Nevertheless, there is a lack of research data to determine the association between alcohol consumption and soft tissue sarcoma. Because soft tissue sarcoma often has poor oncologic and functional outcomes once it develops, identifying controllable factors for prevention would be beneficial. Questions/purposes: (1) Is there a dose-response association between overall alcohol consumption and the incidence of soft tissue sarcoma? (2) Are there associations between the amount of alcohol consumption per occasion and drinking frequency with the incidence of soft tissue sarcomas? Methods: This was a retrospective, population-based comparative study using the National Health Insurance Service database, which offers large-scale data from a relatively ethnically homogeneous Korean population, along with comprehensive health information. The database includes demographic, socioeconomic, health checkups, social behavior surveys, and claims data. We screened 4,234,415 people 20 years or older who underwent health checkups in 2009. Soft tissue sarcoma was defined as ICD-10 codes C47 or C49 and the registration code for cancer (V193), with at least two outpatient claims or more than one inpatient claim per year. Among the screened individuals, we excluded 7% (286,384) because of incomplete data, and we excluded 0.02% (198) with soft tissue sarcoma diagnosed before the index year. To better explore the association, we excluded 0.2% (10,088) of patients who died or developed soft tissue sarcoma in the index year. Finally, we included 3,937,745 participants (2,148,348 males and 1,789,397 females) and followed them until December 31, 2020 (mean follow-up 10 ± 1 years). The mean daily alcohol consumption was calculated using the drinking frequency (number of days per week) and the mean amount consumed on each occasion (the number of glasses [8 grams of ethanol per glass]), based on the concept of a standard drink in Korea. Based on the ethanol consumption, alcohol drinking levels were divided into three categories: individuals who did not drink, those who drank < 30 grams per day of ethanol, and those who drank ≥ 30 grams per day of ethanol. The soft tissue sarcoma incidence was calculated by dividing the number of events by the total person-years of follow-up. To address our primary study question, which was about the association of soft tissue sarcoma incidence and overall alcohol consumption, the analysis model was adjusted for age (years), smoking status (nonsmoker, past smoker, and current smoker), regular exercise (yes versus no), and metabolic syndrome (yes versus no). To address our secondary outcome, which was about associations between the amount of alcohol consumption per occasion and drinking frequency with the incidence of soft tissue sarcomas, alcohol consumption was divided into drinking frequency and amount of alcohol intake per occasion. Among the participants, 969 (males n = 550, females n = 419) were diagnosed with soft tissue sarcoma during the follow-up period, resulting in an incidence of 2.43 (males 2.55, females 2.30) per 100,000 person-years. To identify a monotonic dose-response association, we considered not only the statistical significance for individual exposure groups, but also the overall consistent directional trend in association across all groups. Results: Compared with the individuals who did not drink (reference), alcohol consumption was not associated with an increased incidence of soft tissue sarcoma in overall participants who drank < 30 grams per day and those who drank ≥ 30 grams per day of ethanol (adjusted HR 1.05 [95% confidence interval (CI) 0.9 to 1.22] and adjusted HR 0.92 [95% CI 0.70 to 1.21], respectively; p = 0.58 among three groups) or in males who drank < 30 grams per day and those who drank ≥ 30 grams per day of ethanol (adjusted HR 0.84 [95% CI 0.70 to 1.01] and adjusted HR 0.75 [95% CI 0.56 to 1.00], respectively; p = 0.17 among three groups). In females, compared with individuals who did not drink (reference), soft tissue sarcoma incidence increased in those who drank < 30 grams per day and those who drank ≥ 30 grams per day of ethanol (adjusted HR 1.51 [95% CI 1.20 to 1.9]; p = 0.01 and adjusted HR 2.48 [95% CI 1.17 to 5.27]; p = 0.06, respectively). Although a drinking frequency of 1 to 2 days per week was associated with increased risk of developing a soft tissue sarcoma (adjusted HR 1.61 [95% CI 1.27 to 2.04]; p = 0.003), the HR did not increase with higher drinking frequency across all four groups (adjusted HR 1.21 [95% CI 0.66 to 2.200; p = 0.88 for 3 to 5 days and adjusted HR 1.46 [95% CI 0.47 to 4.56]; p = 0.60 for 6 to 7 days, respectively). However, for females consuming 3 to 4, 5 to 7, and ≥ 14 glasses per occasion, the adjusted HRs were 1.51 (95% CI 1.07 to 2.13; p = 0.09), 1.73 (95% CI 1.16 to 2.58; p = 0.06), and 3.70 (95% CI 1.37 to 9.98; p = 0.03), respectively, and the HR tended to increase with higher consumption levels per occasion across all six groups (adjusted HR 1.30 [95% CI 0.94 to 1.81]; p = 0.09 for 1 to 2 glasses and adjusted HR 1.73 [95% CI 0.81 to 3.68]; p = 0.38 for 8 to 13 glasses). Conclusion: This nationwide population-based study demonstrated a tendency toward a dose-response relationship between the level of alcohol consumption and the incidence of soft tissue sarcoma among females. These findings suggest that strategies for individuals vulnerable to alcohol-related complications could be considered. These...

Cho YJ, et al. Clin Orthop Surg. 2025 Aug;17(4):696-703. https://doi.org/10.4055/cios24350

Background/Objectives: Since the initial approach towards the clinical presentation of soft-tissue masses is challenging for frontline physicians, some countries use clinical practice guidelines. Proper imaging work-up is crucial to differentiate between soft-tissue tumors. Recently, ultrasonography and magnetic resonance imaging (MRI) have been widely used. But there is some controversy about whether pre-referral evaluations are being conducted properly. Thus, this study aims to assess whether the ultrasonography investigation of soft-tissue masses prior to referral to the musculoskeletal tumor center is being performed adequately in terms of indications, diagnostic accuracy, and referral interval, and to evaluate whether the pre-referral MRI for soft-tissue masses is being conducted reasonably concerning indications, imaging protocol, reporting, diagnostic accuracy, and cost-effectiveness. Methods: The study protocol was registered. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist. We performed a database search of the MEDLINE, Embase, and Cochrane Library. Then, two authors reviewed the studies, and the third author resolved any disagreement between them. A total of nine studies were included. The Risk Of Bias In Non-Randomized Studies-of Interventions was applied. Relevant data were extracted by two authors. Results: This review showed that the way that the imaging investigations are performed in non-specialized centers before referral was generally considered inappropriate. Conclusions: Frontline physicians should regard the alarm symptom as an indication for advanced imaging evaluation. Education and certification may be required for ultrasonography. MRI should be performed and interpreted in a specialized center or by a specialist with relevant expertise. Guidance may help reduce inappropriate imaging.

Background: We investigated the normal development of the secondary ossification centers of the acetabulum, focusing on their location and the amount of acetabular coverage increased by them. Methods: We enrolled 132 patients who were 7 to 16 years of age and had no pelvic deformity but did have ≥1 os ischium, os ilium, and/or os pubis on abdominal or pelvic computed tomographic (CT) scans. The locations of the ossification centers were evaluated by adopting an orientation using 0° for the superior acetabulum, 90° for the anterior acetabulum, 180° for the inferior acetabulum, and 270° for the posterior acetabulum, on a reconstructed 3-dimensional (3D) CT image. The acetabular coverage increase by the os ischium, os ilium, or os pubis was defined as the difference in the posterior acetabular sector angle (ΔPASA), posterosuperior acetabular sector angle (ΔPSASA), superior acetabular sector angle (ΔSASA), anterosuperior acetabular sector angle (ΔASASA), or anterior acetabular sector angle (ΔAASA) measured with and without each secondary ossification center. Patients were grouped into 3 age ranges: late childhood, preadolescence, and early adolescence. The location of each ossification center and the increase in acetabular coverage were compared between these groups. Results: In the late-childhood group, the median start-to-end positions in right hips were 269° to 316° for the os ischium, 345° to 356° for the os ilium, and 81° to 99° for the os pubis. These positions tended to be wider in the early-adolescence group at 252° to 328° for the os ischium (p < 0.001), 338° to 39° for the os ilium (p = 0.005), and 73° to 107° for the os pubis (p = 0.049) in right hips. In right hips in the late-childhood group, the median values were 8.1° for ΔPASA, 14.0° for ΔPSASA, 9.9° for ΔSASA, 11.1° for ΔASASA, and 3.9° for ΔAASA; and in the early-adolescence group, the median values in right hips were 10.7° for ΔPASA, 12.9° for ΔPSASA, 8.4° for ΔSASA, 7.4° for ΔASASA, and 5.6° for ΔAASA. Only the median ΔPASA was larger in the early-adolescence group than in the late-childhood group (p = 0.026). Similar results were observed in left hips. Conclusions: In early adolescence, the secondary ossification centers appeared at more extended areas along the acetabular rim, and the increase in acetabular coverage by the secondary ossification centers tended to be larger in the posterior area but not in the anterior or superior area. Level of Evidence: Diagnostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Background: A clear classification of the subtype and grade of soft tissue sarcoma is important for predicting prognosis and establishing treatment strategies. However, the rarity and heterogeneity of these tumors often make diagnosis difficult. In addition, it remains challenging to predict the response to chemotherapy and prognosis. Thus, we need a new method to help diagnose soft tissue sarcomas and determine treatment strategies in conjunction with traditional methods. Genetic alterations can be found in some subtypes of soft tissue sarcoma, but many other types show dysregulated gene expression attributed to epigenetic changes, such as DNA methylation status. However, research on DNA methylation profiles in soft tissue sarcoma is still insufficient to provide information to assist in diagnosis and therapeutic decisions. Questions/purposes: (1) Do DNA methylation profiles differ between normal tissue and soft tissue sarcoma? (2) Do DNA methylation profiles vary between different histologic subtypes of soft tissue sarcoma? (3) Do DNA methylation profiles differ based on tumor grade? Methods: Between January 2019 and December 2022, we treated 85 patients for soft tissue sarcomas. We considered patients whose specimens were approved for pilot research by the Human Biobank of St. Vincent’s Hospital, The Catholic University of Korea, as potentially eligible. Based on this, 41% (35 patients) were eligible; 1% (one patient) was excluded because of gender mismatch between clinical and genetic data after controlling for data quality. Finally, 39 specimens (34 soft tissue sarcomas and five normal samples) were included from 34 patients who had clinical data. All tissue samples were collected intraoperatively. The five normal tissue samples were from muscle tissues. There were 20 female patients and 14 male patients, with a median age of 58 years (range 19 to 82 years). Genomic DNA was extracted from frozen tissue, and DNA methylation profiles were obtained. Genomic annotation of DNA methylation sites and hierarchical cluster analysis were performed to interpret results from DNA methylation profiling. A t-test was used to analyze different methylation probes. Benjamini-Hochberg-adjusted p value calculations were used to account for bias resulting from evaluating thousands of methylation sites. Results: The most common histologic subtypes were liposarcoma (n = 10) and leiomyosarcoma (n = 9). The tumor grade was Fédération Nationale des Centres de Lutte Contre Le Cancer Grades 1, 2, and 3 in 3, 15, and 16 patients, respectively. DNA methylation profiling demonstrated differences between soft tissue sarcoma and normal tissue as 21,188 cytosine-phosphate-guanine sites. Despite the small number of samples, 72 of these sites showed an adjusted p value of < 0.000001, suggesting a low probability of statistical errors. Among the 72 sites, 70 exhibited a hypermethylation pattern in soft tissue sarcoma, with only two sites showing a hypomethylation pattern. Thirty of 34 soft tissue sarcomas were distinguished from normal samples using hierarchical cluster analysis. There was a different methylation pattern between leiomyosarcoma and liposarcoma at 7445 sites. Using the data, hierarchical clustering analysis showed that liposarcoma was distinguished from leiomyosarcoma. When we used the same approach and included other subtypes with three or more samples, only leiomyosarcoma and myxofibrosarcoma were separated from the other subtypes, while liposarcoma and alveolar soft-part sarcoma were mixed with the others. When comparing DNA methylation profiles between low-grade (Grade 1) and high-grade (Grades 2 and 3) soft tissue sarcomas, a difference in methylation pattern was observed at 144 cytosine-phosphate-guanine sites. Among these, 132 cytosine-phosphate-guanine sites exhibited hypermethylation in the high-grade group compared with the low-grade group. Hierarchical clustering analysis showed a division into two groups, with most high-grade sarcomas (28 of 31) separated from the low-grade group and few (3 out of 31) clustered together with the low-grade group. However, three high-grade soft tissue sarcomas were grouped with the Grade 1 cluster, and all of these sarcomas were Grade 2. When comparing Grades 1 and 2 to Grade 3, Grade 3 tumors were separated from Grades 1 and 2. Conclusion: We observed a different DNA methylation pattern between soft tissue sarcomas and normal tissues. Liposarcoma was distinguished from leiomyosarcoma using methylation profiling. High-grade soft tissue sarcoma samples showed a hypermethylation pattern compared with low-grade ones. Our findings indicate the need for research using methylation profiling to better understand the diverse biological characteristics of soft tissue sarcoma. Such research should include studies with sufficient samples and a variety of subtypes, as well as analyses of the expression and function of related genes. Additionally, efforts to link this research with clinical data related to treatment and prognosis are necessary. Level of Evidence: Level III, diagnostic study.

Backgrounds: Determining the precise localization of diseased physes is crucial for guiding the treatment of growth disturbances. Conventional radiography, computed tomography (CT), and magnetic resonance imaging only provide information on physeal anatomy. Planar bone scintigraphy and bone single-photon emission computed tomography (SPECT) resolutions are suboptimal for clinically managing growth disturbances. Bone SPECT/CT, which provides high-resolution functional information, can be a useful tool for evaluating growth disturbances. The purposes of this study were to identify the conditions in which bone SPECT/CT outperforms planar scintigraphy or SPECT for evaluating the location and activity of diseased physes and to assess surgical outcomes using bone SPECT/CT findings in pediatric patients experiencing long bone growth disturbances. Methods: Fifty-nine patients who underwent bone SPECT/CT between January 2018 and January 2021 to evaluate physeal activity using technetium-99 m-labeled 2,3-dicarboxypropane-1,1-diphosphonate (^99mTc-DPD) were included. The proportions of patients for whom certain modalities provided sufficient data for selecting treatment plans for growth disturbances were compared based on the site of the diseased physis, growth disturbance cause, and shape of deformity (i.e., SPECT/CT vs. planar scintigraphy and SPECT/CT vs. SPECT). For assessing surgical outcomes, progression of post-surgical deformity was investigated by measuring the angles reflecting the degree of deformity, iliac crest height difference, or ulnar variance on radiographs. Results: Bone SPECT/CT was sufficient for selecting a treatment plan, but planar scintigraphy or SPECT alone was insufficient in every 10 patients with diseased physes inside the femoral head (p = 0.002) and in every six with physes that were severely deformed or whose locations were unclear on conventional radiography (p = 0.03). In the proximal or distal tibia, where the tibial and fibular physes often overlapped on planar scintigraphy due to leg rotation, bone SPECT/CT was sufficient in 33/34 patients (97%), but planar scintigraphy and SPECT were sufficient in 10/34 (29%) (p < 0.001) and 24/34 (71%) patients, respectively (p = 0.004). No progression or deformity recurrence occurred. Conclusions: Bone SPECT/CT may be indicated in proximal femoral growth disturbance, when the physis is unclear on conventional radiography or severely deformed, the leg exhibits rotational deformity, or the patient is noncompliant.

Background: Lateral condyle fracture of the humerus is the second most common elbow fracture in children. Non-displaced lateral condyle fractures can often be managed with cast and conservative care, while reduction and fixation are often used to treat displaced lateral condyle fractures. Traditionally, K-wire fixation has been used for displaced lateral condyle fractures, but recently fixation using screws has been advocated in some studies. Therefore, we performed a meta-analysis to determine the difference in outcomes and complications between the two different fixation methods for the treatment of displaced lateral condyle fractures of the humerus in pediatric patients. Methods: Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were used for this review. PubMed, Embase, and Cochrane Library were used for study selection. Studies comparing K-wires and screw fixation in displaced lateral condyle fractures in pediatric patients were included. Clinical outcomes using the Hardacre criteria, infection, limitation of range of motion of the elbow, lateral condyle overgrowth, delayed union, nonunion, and avascular necrosis were compared. Data were analyzed using the meta package in R version 4.2.2, and random-effects or fixed-effects models were used according to heterogeneity. Results: One randomized controlled study and three retrospective cohort studies were included, with a total of 240 patients (K-wire:118, screw:122). The clinical outcome using the Hardacre criteria was not different between the groups (P = 0.54), but the risk of infection (risk ratio [RR] = 5.52, 95% CI: 1.42–21.48, P = 0.01) and limitation of range of motion (RR = 3.75, 95% CI: 1.54–9.18, P < 0.01) were significantly higher in the K-wire fixation group than in screw fixation group. Conclusions: The use of screws for fixation after reduction in the treatment of lateral condyle fracture of the humerus in children decreases the risk of superficial infection and elbow stiffness compared with the use of K-wire. Although removal of the implant under general anesthesia is necessary, screw fixation can be considered in displaced lateral condyle fractures of the humerus in children. Trial registration: PROSPERO (CRD42023415643).

주민욱, et al. J Korean Orthop Assoc. 2023 Dec;58(6):485-490. https://doi.org/10.4055/jkoa.2023.58.6.485