Search

PDF file - 3.4MB

Photothermal imaging is useful for detecting individual nanoparticles and obtaining the absorption spectra. This study presents a wide-field photothermal reflectance spectroscopy technique achieved by incorporating a pump beam, a probe beam, and a charge-coupled device (CCD) camera into a commercial microscopic setup. The presented design does not require precise alignment between the pump and the probe beams and enables the observation of numerous individual nanoparticles during image acquisition. Despite the use of a simple imaging processing method, i.e., a four-bucket method using a CCD camera, sufficient sensitivity for the spectral imaging of a single gold nanorod (20 nm diameter and 84 nm length) is demonstrated. Numerous individual nanoparticles within a wide field of view (240 μm × 180 μm) are detected in an image captures at an imaging measurement speed of 0.02 mm2 min−1. Furthermore, the proposed photothermal reflectance spectroscopy technique can detect the variation in the absorption peak of the measured spectra depending on the aspect ratio of individual nanoparticles within a spectral resolution of 1 nm.

Purpose Seoul National University College of Medicine operates a faculty development program for clinical teachers at multiple affiliated teaching hospitals. In 2020, the program was moved online due to coronavirus disease 2019. The purpose of this study was to determine whether it is feasible and effective to provide faculty development programs online in terms of clinical teachers' participation and satisfaction in comparison with offline programs. Methods Clinical teachers participated in the clinical teaching methods programs offline in 2019 and online in 2020. We analyzed participation rate and satisfaction level. All surveys items were rated on a 5-point Likert scale. We also interviewed instructors about the advantages and drawbacks of the online program. Results The participation rate of the online program (89.5%) was significantly higher than that of the offline program (67.8%). The overall satisfaction level for the online program (4.37) was similar to that for the offline program (4.50). Conclusion Faculty development programs online are feasible and effective in medical education. We need to design training content that fits online programs, consider various online training methods to reinforce the strengths of online programs, and support participants to make good use of these programs.

BackgroundActuarial survival based on the Kaplan–Meier method can overestimate actual long-term survival, especially among those with factors of poor prognosis. Patients with American Joint Committee on Cancer stage III soft tissue sarcoma (STS) represent a subset with a high risk of STS-specific mortality. Therefore, we aimed to characterize the clinicopathological characteristics associated with actual long-term survival in patients with stage III STS.MethodsWe retrospectively reviewed 116 patients who underwent surgical resection for stage III STS with curative intent between March 2000 and December 2013. Long-term survivors (n = 61), defined as those who survived beyond 5 years, were compared with short-term survivors (n = 36), who died of STS within 5 years.ResultsMultivariate logistic regression analyses showed that a tumor size p = 0.047], histological grade of 2 (OR 8.12,p = 0.004), and American Society of Anesthesiologists (ASA) score of 1 (OR 11.25,p = 0.001) were independently associated with actual 5-year survival. However, 66% of the long-term survivors exhibited factors of poor prognosis: 36% had a tumor size > 10 cm and 48% had a histological grade of 3. Leiomyosarcoma (3 of 10) was negatively associated with actual long-term survival.ConclusionsActual 5-year survival after resection of stage III STS was associated with tumor size, histological grade, and ASA score. However, majority of the actual 5-year survivors exhibit factors of poor prognosis, suggesting that aggressive treatment should be offered for a chance of long-term survival in these patients.

AimsFor paediatric and adolescent patients with growth potential, preservation of the physiological joint by transepiphyseal resection (TER) of the femur confers definite advantages over arthroplasty procedures. We hypothesized that the extent of the tumour and changes in its extent after neoadjuvant chemotherapy are essential factors in the selection of this procedure, and can be assessed with MRI. The oncological and functional outcomes of the procedure were reviewed to confirm its safety and efficacy.MethodsWe retrospectively reviewed 16 patients (seven male and nine female, mean age 12.2 years (7 to 16)) with osteosarcoma of the knee who had been treated by TER. We evaluated the MRI scans before and after neoadjuvant chemotherapy for all patients to assess the extent of the disease and the response to treatment.ResultsThe mean follow-up period was 64.3 months (25 to 148) after surgery and no patients were lost to follow-up. On MRI evaluation, 13 tumours were near but not in contact with the physes and three tumours were partially in contact with the physes before neoadjuvant chemotherapy. Bone oedema in the epiphysis was observed in eight patients. After neoadjuvant chemotherapy, bone oedema in the epiphysis disappeared in all patients. In total, 11 tumours were not in contact and five tumours were in partial contact with the physes. The postoperative pathological margin was negative in all patients. At the last follow-up, 12 patients were continuously disease-free and three had no evidence of disease. One patient died due to the disease. Functionally, the patients with retained allograft or recycled autograft had a mean knee range of flexion of 126° (90° to 150°). The mean Musculoskeletal Tumor Society functional score was 27.6 (23 to 30).ConclusionTER is an effective limb-salvage technique for treating malignant metaphyseal bone tumours in paediatric and young osteosarcoma patients with open physes when a good response to chemotherapy and no progression of the tumour to the epiphysis have been confirmed by MRI. Cite this article: Bone Joint J 2020;102-B(6):772–778.

Backgroud Cancer stem cells (CSCs) are cells characterized by their self-renewal and tumorigenic potential. The purpose of this study was to discover the role of the delta-like factor 1 (DLK1) in sarcoma. Methods mRNA expression of DLK1 from 13 sarcoma cell lines was examined. Isolated CSCs from the tumors were examined using fluorescence-activated cell sorting (FACS) with CD133, the CSC marker, or sphere-forming assay. The relationship between DLK1 and CSCs in sarcoma was examined using cell proliferation and cell invasion assays after they were treated with DLK1 short interfering RNA (siRNA). Results A high expression of DLK1 mRNA was observed in all sarcoma cell lines. However, CSCs were isolated from over expressed sarcomas of the DLK1 gene, and they have shown to be expressed lower than the wild type. The anti-cancer effects of DLK1 siRNA inhibited cell proliferation and invasion in U2OS, A204, and sw872. In addition, treatment with DLK1 siRNA inhibited cell invasion in sw872 CSCs. DLK1 gene induces tumorigenesis in various sarcoma cells and regulates the invasiveness of liposarcoma. These results suggest that DLK1 could serve as a possible therapeutic target for sarcoma. Conclusions Our study showed that the DLK1 gene induces tumorigenesis in various sarcomas and is associated with invasive mechanism in sarcoma. These results suggest DLK1 could serve as a possible therapeutic target in a variety of sarcomas.

In this paper, we propose a sensitivity-enhanced thermoreflectance microscopy (TRM) system employing an electronic auto-balancing photoreceiver for effective thermal fault localization through a Si substrate. The proposed system in the auto-balanced detection not only improves the system signal-to-noise ratio (SNR) by approximately five times compared to that achievable via normal detection but also mitigates the inherent system noise, such as pseudothermoreflectance signals, by using the optical zooming. Moreover, temperature variations as small as ~47 mK were detectable under the measurement conditions employed in this paper. Finally, we experimentally demonstrated clear localization of a thermal fault, which was dimly visible in the normal backside detection results, in an optical zoomed thermal image.

Background Spontaneous disease stabilization of desmoid-type fibromatosis (DF) has been demonstrated in many reports, and the watchful waiting approach without any frontline treatment is becoming popular as an initial management strategy. In this study, we aimed to assess the disease stabilization rate and identify predictive factors for disease stabilization of DF in patients with conservative treatment. Methods We reviewed 76 patients with sporadic extra-abdominal DF who were managed with frontline conservative treatment in our institute. The minimum follow-up was 12 months. Stabilization was defined as radiological evidence of no change or continuous decrease in size of the tumor for six months or more. The primary endpoint was stabilization of DF. Possible patient-, disease-, and treatment-related factors predictive of disease stabilization were analyzed with multivariate analysis. Results At final follow-up, 54 of the 76 tumors (71%) were stable, and mean time to stabilization was 30.4 months (range, 7 to 112 months). On Kaplan-Meier survival analysis, the spontaneous stabilization rate was 25.4% at one year, 52.7% at two years, and 70.9% at three years. The mean time to spontaneous stabilization was longer in patients with ≤ 40 years of age (p = 0.022) or recurrence (p = 0.041). On multivariate analysis with the Cox proportional hazard method, recurrence (hazard ratio [HR], 1.79; p = 0.041) and younger age (HR, 2.04; p = 0.022) were identified as independent prognostic factors for longer time to disease stabilization. Conclusions Frontline conservative treatment seems to be the optimal treatment for most patients with DF. Younger patients or those with recurrence may require longer time to spontaneous disease stabilization.

Purpose The role of chemotherapy (CT) and radiotherapy (RT) for management of extraskeletal osteosarcoma (ESOS) remains controversial. We examined disease outcomes for ESOS patients and investigated the association between CT/RT with recurrence and survival. Patients and methods Retrospective review at 25 international sarcoma centers identified patients ≥18 years old treated for ESOS from 1971 to 2016. Patient/tumour characteristics, treatment, local/systemic recurrence, and survival data were collected. Kaplan–Meier survival and Cox proportional-hazards regression and cumulative incidence competing risks analysis were performed. Results 370 patients with localized ESOS treated definitively with surgery presented with mainly deep tumours (n = 294, 80%). 122 patients underwent surgical resection alone, 96 (26%) also received CT, 70 (19%) RT and 82 (22%) both adjuvants. Five-year survival for patients with localized ESOS was 56% (95% CI 51%–62%). Almost half of patients (n = 173, 47%) developed recurrence: local 9% (35/370), distant 28% (102/370) or both 10% (36/370). Considering death as a competing event, there was no significant difference in cumulative incidence of local or systemic recurrence between patients who received CT, RT, both or neither (local p = 0.50, systemic p = 0.69). Multiple regression Cox analysis showed a significant association between RT and decreased local recurrence (HR 0.46 [95% CI 0.26–0.80], p = 0.01). Conclusion Although the use of RT significantly decreased local recurrences, CT did not decrease the risk of systemic recurrence, and neither CT, nor RT nor both were associated with improved survival in patients with localized ESOS. Our results do not support the use of CT; however, adjuvant RT demonstrates benefit in patients with locally resectable ESOS.

This publisher’s note contains corrections to Opt. Lett. 46, 4216 (2021)OPLEDP0146-959210.1364/OL.432413.

Wavelength-tunable optical vortices with a topological charge equal to l = 1 of orbital angular momentum (OAM) were experimentally realized using a single off-axis spiral phase mirror (OSPM) with lasers of various visible-light wavelengths. Using an OSPM designed for 561 nm and an incidence angle of 45°, circular doughnut-shaped l = 1 optical vortices were obtained at 561, 473, and 660 nm by rotating the OSPM to modify the laser incidence angle. Wavelength-tunable l = 1 optical vortices were obtained at the respective incidence angles of 45°, 53.4°, and 33.7°, because the effective geometrical thickness of the OSPM, which determines the order of OAM, was identical at each wavelength. This flexible OSPM which operates over a wide wavelength range will provide continuously wavelength-tunable optical vortices for applications in the fields of advanced optics and photonics in which optical vortices with wide wavelength tunability are in demand.

Clear cell chondrosarcoma (CCC) is a rare subtype of chondrosarcoma with a relatively low malignant potential, mainly diagnosed by its characteristic location in the epiphysis of long bones. We report the case of a 33-year-old gentleman who presented with pain, difficulty in walking and restricted range of motion of the right hip joint, with a lesion located in the proximal femoral metaphysis and completely sparing the epiphysis. Needle biopsy was consistent with CCC, which was extremely unusual considering the location of the tumour. The patient was treated by “en bloc” resection of the tumour along with femoral head and reconstruction with hemiarthroplasty. The final histopathology report confirmed the diagnosis with clear surgical margins. The aim of this case report and literature review was to highlight the unusual location of this rare tumour, as such an isolated case of CCC completely sparing the epiphysis has never been reported.

Background Postoperative ambulation recovery after surgery for femur metastases has significant implications for not only the patient's quality of life but also administration of further cancer treatment. Thus, identification of preoperative predictors of ambulation recovery is necessary to set appropriate expectations and guide treatment. This study aimed to assess ambulation recovery rate and identify predictors of ambulation recovery in patients undergoing surgery for femur metastases. Materials and Methods A total of 244 patients who underwent surgery for femur metastases at our institution were reviewed. Patients were considered ambulatory if they were able to walk independently or walk with aids and nonambulatory if they were wheelchair bound or bedridden. The following potential clinicopathologic factors that might predict postoperative ambulation recovery were evaluated: premorbid general status, cancer burden, and local factors. Results A total of 165 patients (68%) regained ambulatory status postoperatively. A multivariate analysis revealed poor Eastern Cooperative Oncology Group (ECOG) performance status (odds ratio [OR], 5.327; p, Postoperative ambulation recovery has significant implications for a patient's quality of life as well as for further cancer treatment. This article reports on predictive factors of postoperative ambulation recovery after surgery for femur metastases.

Background Despite the overall diagnostic utility of core needle biopsy (CNB) comparable to incisional biopsy, increased diagnostic errors have been suggested of CNB for myxoid soft tissue tumors. This study compared the diagnostic performance of CNB between myxoid and non-myxoid soft tissue tumors. Methods 369 patients who underwent ultrasound-guided CNB prior to resection for soft tissue tumors were classified into two groups according to resection pathology; myxoid group (n = 75) and non-myxoid group (n = 294). One-hundred and ninety-three patients were male and the median age of the patients was 40 years. Two-hundred and sixty-three tumors were malignant. Results CNB correctly diagnosed malignancy in 84% (58 of 69) for the myxoid group and 95% (184 of 194) for the non-myxoid group. For diagnosing histologic grade of soft tissue sarcoma, CNB correctly identified high grade in 78% (18 of 23) for the myxoid group and 74% (94 of 128) for the non-myxoid group. Correct diagnosis rate of histological type was significantly lower in the myxoid group (63% [47 of 75] in the myxoid group and 83% [242 of 294] in the non-myxoid group, p = 0.013). Conclusion Our study suggests that CNB is useful for myxoid soft tissue tumors of the extremity, with regard to diagnosing malignancy and histologic grade. However, CNB was less useful for identifying histologic subtype in myxoid tumors than in non-myxoid tumors.

Precise mechanisms underlying interleukin-7 (IL-7)-mediated tumor invasion remain unclear. Thus, we investigated the role of IL-7 in tumor invasiveness using metastatic prostate cancer PC-3 cell line derivatives, and assessed the potential of IL-7 as a clinical target using a Janus kinase (JAK) inhibitor and an IL-7-blocking antibody. We found that IL-7 stimulated wound-healing migration and invasion of PC-3 cells, increased phosphorylation of signal transducer and activator of transcription 5, Akt, and extracellular signal-regulated kinase. On the other hand, a JAK inhibitor and an IL-7-blocking antibody decreased the invasiveness of PC-3 cells. IL-7 increased tumor sphere formation and expression of epithelial–mesenchymal transition (EMT) markers. Importantly, lentiviral delivery of IL-7Rα to PC-3 cells significantly increased bone metastasis in an experimental murine metastasis model compared to controls. The gene expression profile of human prostate cancer cells from The Cancer Genome Atlas revealed that EMT pathways are strongly associated with prostate cancers that highly express both IL-7 and IL-7Rα. Collectively, these data suggest that IL-7 and/or IL-7Rα are promising targets of inhibiting tumor metastasis.

Purpose To identify prognostic factors influencing progression-free survival (PFS) of aggressive fibromatosis (AF) after postoperative radiotherapy (PORT) and assess correlations between immunohistochemistry (IHC) features of β-catenin/smooth muscle actin (SMA) and PFS. Materials and Methods Records of 37 patients with AF treated by PORT from 1984 to 2015 were retrospectively reviewed. Fifteen patients underwent wide excision for AF and 22 patients received debulking operation. The median total dose of PORT was 59.4 Gy. IHC staining results of β-catenin and SMA were available for 11 and 12 patients, respectively. Results The median follow-up duration was 105.9 months. Five-year PFS rate was 70.9%. Tumor size or margin status was not related to PFS in univariate analysis (p = 0.197 and p = 0.716, respectively). Multivariate analysis showed that increased interval from surgery to PORT (>5.7 weeks) was a marginal risk factor for PFS (p = 0.054). Administration of PORT at the initial diagnosis resulted in significantly improved PFS compared to deferring PORT after recurrence (p = 0.045). Patient with both risk factors of deferring PORT after recurrence and interval from surgery to PORT >5.7 weeks had significantly lower 5-year PFS than patients without risk factor (34.1% vs. 100.0%; p = 0.012). Nuclear β-catenin intensity tended to inversely correlate with 5-year PFS, although it did not reach statistical significance (62.5% at low vs. 100.0% at high; p = 0.260). SMA intensity was not related to PFS (p = 0.700). Conclusion PORT should be performed immediately after surgery irrespective of margin status or tumor size especially in recurrent case. Nuclear β-catenin staining intensity of IHC might correlate with local recurrence.

Introduction The role of MRI in surveillance for local recurrence (LR) remains uncertain in extremity soft tissue sarcoma (STS). The aims of this study were 1) to examine the usefulness of MRI in detecting LR, 2) to identify the characteristics of LR detected by MRI, and 3) to examine whether MRI surveillance is associated with oncologic outcome. Materials and Methods 477 patients who had regular surveillance for LR after surgery for extremity STS were reviewed. Surveillance was performed by routine MRI in 325 patients or other imaging modalities in 152 patients. Results The rate of MRI-detected LR, defined as clinically undetectable LR identified on MRI, was 10.5% in the MRI surveillance cohort. The detection rates of MRI-detected LR were significantly higher in the patients with high risk of LR. MRI-detected LRs were more commonly located in the thigh or buttock (p = 0.005), were smaller (p = 0.001) and had LRs without mass formation (p = 0.007) than non-MRI-detected LRs. On Kaplan-Meier analysis, patients with MRI-detected LR tended to have better post-LR survival (p = 0.104). Conclusion Routine MRI surveillance can detect a significant number of clinically undetectable LRs in extremity STS especially for LRs in the thigh or buttock, small LRs or LRs without mass formation.

Purpose/Objective(s) Radiation-induced sarcoma (RIS) is a rare secondary malignancy resulting from ionizing radiation-related treatment after a long latency period. Despite the unfavorable clinical outcomes, the genomic footprints of ionizing radiation in RIS development remain largely unknown. Hence, this study aimed to characterize RIS genomes and the genomic alterations in them. Materials/Methods We performed whole-genome sequencing (WGS) of 11 cases of RIS matched with normal genomes to identify somatic alterations potentially associated with RIS development. Results The mutation abundance of RIS genomes including one hypermutated genome was variable. Cancer-related genes might show different types of genomic alterations. For instance, NF1, NF2, NOTCH1, NOTCH2, PIK3CA, RB1, and TP53 showed singleton somatic mutations; MYC, CDKN2A, RB1, and NF1 showed recurrent copy number alterations; and NF2, ARID1B, and RAD51B showed recurrent structural variations (SVs). The effects of non-homologous end joining on short insertions-deletions and SVs were substantial in RIS genomes, compared with in spontaneous osteosarcoma genomes, representing the genomic hallmark of RIS genomes. In addition, frequent chromothripsis and predisposing germline variants in DNA damage-repair pathways were identified. Conclusion Taken together, WGS-scale characterization of RIS genomes may pave the way for advanced diagnostic and therapeutic strategies for RIS.

For paediatric and adolescent patients with growth potential, preservation of the physiological joint by transepiphyseal resection (TER) of the femur confers definite advantages over arthroplasty procedures. We hypothesized that the extent of the tumour and changes in its extent after neoadjuvant chemotherapy are essential factors in the selection of this procedure, and can be assessed with MRI. The oncological and functional outcomes of the procedure were reviewed to confirm its safety and efficacy.We retrospectively reviewed 16 patients (seven male and nine female, mean age 12.2 years (7 to 16)) with osteosarcoma of the knee who had been treated by TER. We evaluated the MRI scans before and after neoadjuvant chemotherapy for all patients to assess the extent of the disease and the response to treatment.The mean follow-up period was 64.3 months (25 to 148) after surgery and no patients were lost to follow-up. On MRI evaluation, 13 tumours were near but not in contact with the physes and three tumours were partially in contact with the physes before neoadjuvant chemotherapy. Bone oedema in the epiphysis was observed in eight patients. After neoadjuvant chemotherapy, bone oedema in the epiphysis disappeared in all patients. In total, 11 tumours were not in contact and five tumours were in partial contact with the physes. The postoperative pathological margin was negative in all patients. At the last follow-up, 12 patients were continuously disease-free and three had no evidence of disease. One patient died due to the disease. Functionally, the patients with retained allograft or recycled autograft had a mean knee range of flexion of 126° (90° to 150°). The mean Musculoskeletal Tumor Society functional score was 27.6 (23 to 30).TER is an effective limb-salvage technique for treating malignant metaphyseal bone tumours in paediatric and young osteosarcoma patients with open physes when a good response to chemotherapy and no progression of the tumour to the epiphysis have been confirmed by MRI. Cite this article

Postoperative delirium (PD), characterized by acute onset of global impairment in consciousness and cognition, is a common complication following major surgeries and is often associated with adverse outcomes. Because of the multiple comorbidities of the patient along with extensive nature of the surgery, patients undergoing surgery for bone metastases may be prone to developing PD. However, no study exists regarding PD in patients who undergo surgery for bone metastases. Two hundred seventy six patients with mean age of 64 years (range, 16–94) who underwent surgery for bone metastases were reviewed. The diagnosis of PD was made by the psychiatrist, according to fourth edition of the Diagnostic and Statistical Manual of Mental Disorders. Possible perioperative clinic-pathologic factors that may be associated with the development of PD were investigated. Among the 276 patients, 9% (n = 25) developed PD. On multivariate logistic regression analysis, history of psychiatric disorders (odds ratio [OR] = 9.63; 95% confidence interval [CI] 1.78–21.74, P = .004), high preoperative serum C-reactive protein (CRP) level (OR = 1.17; 95% CI 1.06–1.29, P = .001), low preoperative serum albumin level (OR = 0.13; 95% CI 0.03–0.48, P = 0.002), and high dose of opioid analgesics received in the immediate postoperative period (OR = 1.05; 95% CI 1.01–1.07, P = .001) were independently associated with the development of PD. Patients with PD had lower survival (log rank, P = .001) than patients without PD. Incidence of PD is considerable in patients undergoing surgery for bone metastases. History of psychiatric disorders, preoperative serum albumin and CRP levels, and the dose of postoperative opioid analgesics are associated with the development of PD.

To analyze the treatment outcomes and the effects of adjuvant radiotherapy (RT) in patients with synovial sarcoma (SS). The medical records of 103 patients treated with definitive surgery for SS, with/without RT, from August 1982 to July 2013 were reviewed retrospectively. The median age of the patients was 33 years (range, 5 to 72 y). The most frequent tumor location was the extremities (79 patients, 77%). Seventy-five patients (73%) received adjuvant RT and 26 (25%) did not. The median dose of adjuvant RT was 61.2 Gy (range, 45 to 66.6 Gy). The median follow-up period was 5.4 years (range, 0.2 to 31.0 y). The 5- and 10-year overall survival rates were 77 % and 65%, respectively. The progression-free survival (PFS) rates at 5 and 10 years were 52% and 43%, respectively. The most common site of initial failure was the lung (24 patients), followed by local recurrence (14 patients). The 5-year local-recurrence-free survival (LRFS) and distant-metastasis-free survival (DMFS) rates were 80% and 63%, respectively. On multivariate analysis, a mitosis count of

Objectives We evaluated the accuracy of augmented reality (AR)-based navigation assistance through simulation of bone tumours in a pig femur model. Methods We developed an AR-based navigation system for bone tumour resection, which could be used on a tablet PC. To simulate a bone tumour in the pig femur, a cortical window was made in the diaphysis and bone cement was inserted. A total of 133 pig femurs were used and tumour resection was simulated with AR-assisted resection (164 resection in 82 femurs, half by an orthropaedic oncology expert and half by an orthopaedic resident) and resection with the conventional method (82 resection in 41 femurs). In the conventional group, resection was performed after measuring the distance from the edge of the condyle to the expected resection margin with a ruler as per routine clinical practice. Results The mean error of 164 resections in 82 femurs in the AR group was 1.71 mm (0 to 6). The mean error of 82 resections in 41 femurs in the conventional resection group was 2.64 mm (0 to 11) (p < 0.05, one-way analysis of variance). The probabilities of a surgeon obtaining a 10 mm surgical margin with a 3 mm tolerance were 90.2% in AR-assisted resections, and 70.7% in conventional resections. Conclusion We demonstrated that the accuracy of tumour resection was satisfactory with the help of the AR navigation system, with the tumour shown as a virtual template. In addition, this concept made the navigation system simple and available without additional cost or time. Cite this article: H. S. Cho, Y. K. Park, S. Gupta, C. Yoon, I. Han, H-S. Kim, H. Choi, J. Hong. Augmented reality in bone tumour resection: An experimental study. Bone Joint Res 2017;6:137–143.

Due to minimal tissue violation in percutaneous core needle biopsy (CNB), in contrast to open biopsy, the risk of tumor seeding and subsequent local recurrence (LR) along the biopsy tract remains unclear in extremity soft tissue sarcoma (STS). This study sought to examine the association of CNB tract resection on LR in a large STS institutional database. After a retrospective review of the 116 patients who underwent CNB prior to surgery for previously untreated non-metastatic extremity STS, 36 patients who did not have CNB tracts resected (CNB-NR) were matched with 36 who had CNB tracts resected (CNB-R) for the factors that are known to affect LR. Two patients (6%) developed LR in the CNB-R group, whereas three patients (8%) developed LR in the CNB-NR group (P = 0.643). On Kaplan-Meier analysis, there was no significant difference in LR-free survival between the two groups (94.3% ± 3.9 for the CNB-R group vs. 93.8% ± 4.3 for the CNB-NR group, P = 0.747). Our data suggest any influence of a CNB tract resection on LR, within the limitations of this study, is likely to be of minor clinical importance in extremity STS. Although it would be prudent to resect the CNB tract in most cases, not resecting the CNB tract is a feasible option if identification or removal of the CNB tract proves difficult.

Soft tissue sarcoma (STS) with an infiltrative histologic growth pattern, when compared to STS with an expansile pattern, may pose difficulties in local control. Preoperative assessment of the presence of infiltrative histologic growth pattern would be helpful in deciding treatment strategies. A review of 144 patients who underwent surgery for extremity STS was performed. Microscopically, the histologic growth pattern was defined as infiltrative if the penetration of the tumor cells into the surrounding tissue was observed. Possible clinicopathologic factors that might be associated with infiltrative histologic growth pattern were investigated with regard to patient demographics, tumor characteristics, and MRI findings. Of the 144 tumors, 71 (49%) showed infiltrative histologic growth pattern. On multivariate analysis, histological subtypes other than liposarcoma (OR = 4.57,p=0.02) and infiltrative border on MRI (OR = 2.48,p=0.01) were independent factors associated with infiltrative histologic growth pattern. Predictive index based on these two factors showed a significant improved accuracy (ROC-AUC = 0.647) for predicting infiltrative histologic growth pattern compared to either factor alone. Our data suggests that liposarcoma histology and tumor border on MRI can predict histologic growth pattern in extremity STS.

Background Superficial soft tissue sarcoma (S-STS) has been reported to have more favorable prognoses than deep-seated STS. However, for some patients, poor prognoses have been observed and there is a need for better prognostication. The deep peripheral fascia lies in the border of the S-STS and can be consistently detected using magnetic resonance imaging (MRI). The relationship of the subcutaneous tumor with the fascia on MRI scan was reported to be useful in classifying the tumor as benign or malignant; this in turn, may reflect the biological aggressiveness of STS. This study was performed to evaluate the oncologic outcomes and to identify the prognostic factors of S-STS by focusing on the relationship of S-STS with the underlying fascia on MRI. Material and methods We retrospectively reviewed data on 253 patients who underwent resection of localized S-STS. Potential factors that might influence the oncologic outcomes were identified. The fascia-tumor relationship on MRI was classified into three groups: no fascial contact group (n = 46), fascial contact group (n = 77), and fascial invasion group (n = 84). Results Overall, 39 patients (16.5%) died due to S-STS; the 5- and 10-year survival rates were 82.6 ± 2.9% and 73.2 ± 4.5%, respectively. Fascial invasion detected on MRI scans (OR = 2.190, p = 0.034) and advanced age (OR = 2.408, p = 0.034) were found to be independent factors for worse disease specific survival. The fascia-tumor relationship on MRI scan was not associated with local recurrence of S-STS. Conclusion The fascia-tumor relationship on MRI scan reflects the biological aggressiveness of S-STS and can serve as a prognostic factor.

Background While survival after surgical treatment of extremity soft tissue sarcoma (STS) is traditionally reported as actuarial survival, conditional survival (CS) may be more clinically relevant as it accounts for time already survived. We compared actuarial survival and CS of STS patients. Materials and methods We analyzed 567 patients who underwent surgery for localized extremity STS. Actuarial survival was estimated using the Kaplan-Meier method. Cox proportional hazards model was used to evaluate factors associated with disease-specific survival. Five-year CS (CS5) estimates at "χ" year(s) after surgery were calculated as CS5 = S(χ + 5)/S(χ). Results Whereas actuarial survival decreased over time, CS5 increased. The postsurgical 1-, 3-, and 5-year CS5 values were 84.5%, 90.0%, and 93.8%, respectively, whereas the 6-, 8-, and 10-year actuarial survival rates were 82.0%, 79.4%, and 78.5%, respectively. The calculated CS5 exceeded actuarial survival especially in patients with risk factors such as large tumor size and Federation Nationale des Centers de Lutte Contre le Cancer (FNCLCC) grades 2 and 3 tumors. Patients with tumor size ≥5 cm had an actuarial survival of 73.9% at 10 years compared to a CS5 of 95.4% in patients alive at 5 years. Likewise, patients with FNCLCC grade 3 tumors had an actuarial survival of 71.1% at 10 years compared to a CS5 of 96.0% in patients alive at 5 years. Conclusions Survival estimation by determination of CS can be dynamic and accurate especially in high-risk patients. CS can be useful for survival prediction and clinical decision making in extremity STS patients.

BACKGROUND Application of surgical navigation for pelvic bone cancer surgery may prove useful, but in addition to the fact that research supporting its adoption remains relatively preliminary, the actual navigation devices are physically large, occupying considerable space in already crowded operating rooms. To address this issue, we developed and tested a navigation system for pelvic bone cancer surgery assimilating augmented reality (AR) technology to simplify the system by embedding the navigation software into a tablet personal computer (PC). QUESTIONS/PURPOSES Using simulated tumors and resections in a pig pelvic model, we asked: Can AR-assisted resection reduce errors in terms of planned bone cuts and improve ability to achieve the planned margin around a tumor in pelvic bone cancer surgery? METHODS We developed an AR-based navigation system for pelvic bone tumor surgery, which could be operated on a tablet PC. We created 36 bone tumor models for simulation of tumor resection in pig pelves and assigned 18 each to the AR-assisted resection group and conventional resection group. To simulate a bone tumor, bone cement was inserted into the acetabular dome of the pig pelvis. Tumor resection was simulated in two scenarios. The first was AR-assisted resection by an orthopaedic resident and the second was resection using conventional methods by an orthopaedic oncologist. For both groups, resection was planned with a 1-cm safety margin around the bone cement. Resection margins were evaluated by an independent orthopaedic surgeon who was blinded as to the type of resection. All specimens were sectioned twice: first through a plane parallel to the medial wall of the acetabulum and second through a plane perpendicular to the first. The distance from the resection margin to the bone cement was measured at four different locations for each plane. The largest of the four errors on a plane was adopted for evaluation. Therefore, each specimen had two values of error, which were collected from two perpendicular planes. The resection errors were classified into four grades: ≤ 3 mm; 3 to 6 mm; 6 to 9 mm; and > 9 mm or any tumor violation. Student's t-test was used for statistical comparison of the mean resection errors of the two groups. RESULTS The mean of 36 resection errors of 18 pelves in the AR-assisted resection group was 1.59 mm (SD, 4.13 mm; 95% confidence interval [CI], 0.24-2.94 mm) and the mean error of the conventional resection group was 4.55 mm (SD, 9.7 mm; 95% CI, 1.38-7.72 mm; p < 0.001). All specimens in the AR-assisted resection group had errors < 6 mm, whereas 78% (28 of 36) of errors in the conventional group were < 6 mm. CONCLUSIONS In this in vitro simulated tumor model, we demonstrated that AR assistance could help to achieve the planned margin. Our model was designed as a proof of concept; although our findings do not justify a clinical trial in humans, they do support continued investigation of this system in a live animal model, which will be our next experiment. CLINICAL RELEVANCE The AR-based navigation system provides additional information of the tumor extent and may help surgeons during pelvic bone cancer surgery without the need for more complex and cumbersome conventional navigation systems.

Background: The impact of surgical margin status on the survival of patients with extremity soft tissue sarcoma (STS) remains to be clearly defined. The evidence regarding the impact of surgical margins on survival is limited by retrospective single-institution cohort studies. We conducted a systematic review and meta-analysis to examine the impact of surgical margin status on patient survival in extremity STS. Methods: A literature search in the PubMed, EMBASE, and Cochrane Controlled Trials Register electronic databases, and a manual search of reference lists of original studies was performed. The following text words and/or Medical Subject Heading terms were searched: (neoplasm) or/and (sarcoma) and/or (connective tissue) and/or (soft tissue) and/or (extremity) and/or (extremity) and/or (surgical margin). Results: Six selected studies that reported a total of 2917 cases of extremity STS were published between 1994 and 2013. All the eligible studies were observational cohort studies, and the sample size ranged from 95 to 1261 patients. A meta-analysis of 6 studies showed that a positive surgical margin predicted poor 5-year OS in a random-effects model (summary hazard ratio, 1.56; 95% confidence interval, 1.12–2.17). Moderate heterogeneity was observed among the studies (P

In laser-plasma interactions (LPI), the laser beam mode is a critical parameter when trying to explore new physical phenomena. Of the various spatial beam modes, the Laguerre-Gaussian (LG) mode with vortex phase has attracted considerable attention due to its unique features, including the ability to carry an orbital angular momentum. Due to this, it has been actively applied to LPI, which mainly utilize ultrashort intense laser pulses. However, existing transmissive phase-manipulating optical elements have several limitations when applied in LPI due to critical issues such as pulse broadening, attenuation, and beam shape–all of which have an influence on the beam quality, as well as, geometry, size, simplicity, and cost–all of which are related to processing technologies. In this paper, we present a series of procedures to obtain high-quality low-order (l = 1 and 2) LG vortex beams from large-sized off-axis reflective spiral phase plates (ORSPPs). The geometric designs for various surface structures, electromagnetic wave simulations in the extra-large domain, hybrid-mechanical processing technique attempted newly, and experimental demonstrations are involved. Experimental observations of LG intensity distributions and interference fringes were verified with the simulation results of Poynting vector, phase, and angular momentum densities. The beam quality of LG intensity distributions was analyzed quantitatively through the investigation of an annular zone formed from the uniformity of the stepped and continuous surface structures of ORSPPs. Furthermore, we numerically investigated the physical phenomena on the high-intensity angular momentum transfer from light to matter, considering ORSPP–driven low-order LG vortex laser pulses, by performing 3D particle-in-cell simulations.

Background Endoprosthetic reconstruction is widely applied for pathological fractures of the proximal humerus; however, functional impairment is usually unsatisfactory. The aims of the current study are to evaluate the reliability of interlocking intramedullary (IM) nailing with cement augmentation as a fixation method in proximal humeral lesions and to assess functional outcomes. Methods We reviewed 32 patients with pathological fractures of the proximal humerus who underwent interlocking IM nailing and cement augmentation. Functional scores and pain relief were assessed as outcomes. Results The mean follow-up period was 14.2 months. The mean Musculoskeletal Tumor Society functional score and Karnofsky performance status scale score were 27.7 and 75.6, respectively. Improvement of pain assessed using the visual analogue scale was 6.2 on average. Thirty-one patients (97%) experienced no pain after surgery. The mean ranges of forward flexion and abduction were 115° and 112.6°, respectively. All patients achieved stability and had no local recurrence without failure of fixation until the last follow-up. Conclusions Proximal interlocking IM nailing with cement augmentation appears to be a reliable treatment option for pathological or impending fractures of the proximal humerus in selected patients with metastatic tumors, even with extensive bone destruction.

Background Understanding the incidence and characteristics of multiple primary malignancies (MPM) has implications for guiding appropriate treatment and surveillance of extremity soft tissue sarcoma (STS). Objectives We sought to examine the incidence of MPM in STS (MPM-STS), and compare their clinicopathologic characteristics and survival to those with STS only. Methods 585 patients who underwent surgery for extremity STS were reviewed. Logistic regression analyses to identify factors contributing to the development of MPMs and a 1:2 matched case–control analysis to compare survival outcome were performed. Results Of the 585 patients analyzed, 34 (6%) with MPM were identified. On univariate logistic regression analysis, older age (>49 years) at STS diagnosis (p = 0.008) and histologic types of undifferentiated pleomorphic sarcoma or myxofibrosarcoma (p = 0.033) were significant. In multivariate analysis, only older age at STS diagnosis remained significant (OR = 2.5, p = 0.029). Cancer-specific survival of the MPM-STS group was significantly lower than that of the STS-only group (p = 0.031). However, there was no significant difference in STS-specific survival between the two groups (p = 0.208). Conclusion Our study suggests that MPM is not uncommon in extremity STS and older age at STS diagnosis is associated with risk of MPM. Prognosis of STS in the MPM-STS group seems similar to that of the STS-only group.

BACKGROUND Our study of a large patient group reports on the behavior and postoperative recurrence of osteofibrous dysplasia (OFD). METHODS We reviewed the medical records of 55 patients who were diagnosed with OFD of the tibia and showed typical features of this tumor. The patients' presentation, disease course, history of pathologic fracture, typical radiographic features, surgical treatment history, and surgical results were investigated. RESULTS The longitudinal OFD lesion size peaks at a mean 13.3 years of age with a mean maximum proportionate size of 0.33. These lesions in 92% of the patients spontaneously presented with a stable disease course, while those in the other 8% continued increasing. There were no significant predictive factors of disease course. Among surgically treated lesions, we noted a higher rate of recurrence after curettage than after excision (P

Tumor-propagating cells (TPCs) are believed to drive cancer initiation, progression and recurrence. These cells are characterized by enhanced tumorigenicity and self-renewal. The ability to identify such cells in primary human sarcomas relies on the dye exclusion ability of tumor side population (SP) cells. Here, we performed a high-throughput cell surface antigen screen and found that CD146 is enriched in the SP population. In vivo serial transplantation assays showed that CD146+ cells are highly tumorigenic, capable of self-renewal and thus enriches for the TPC population. In addition, depletion of SP cells from the CD146+ population show that CD146+ cells and SP cells are a distinct and overlapping TPC populations. Gene expression profiling of CD146+ and SP cells revealed multiple pathways commonly upregulated in both of these populations. Inhibition of one of these upregulated pathways, Notch signaling, significantly reduced tumor growth and self-renewal. Our data demonstrate that CD146 is an effective cell surface marker for enriching TPCs in primary human sarcomas. Targeting differentially activated pathways in TPCs may provide new therapeutic strategies for treating sarcoma.

Purpose The purpose of this study is to report on the incidence and the experience in management of radiation-induced sarcoma (RIS) at a large single center in Korea for 15 years. Materials and methods We retrospectively reviewed the sarcoma registry of a large institution from January 2000 to April 2014. Results Out of the 3,674 patients listed in the registry, 33 patients (0.9%) diagnosed with RIS were identified. The median latency of RIS was 12.1 years. The number of cases of RIS increased from four cases in the years 2000-2003 to 14 cases in the years 2012-2014. The most common histology was osteosarcoma (36.4%). The median follow-up period was 23.1 months, the median overall survival (OS) of all patients was 2.9 years, and their 5-year survival rate was 44.7%. Univariate and multivariate analyses showed association of the age at diagnosis (p=0.01) and the treatment aim (p=0.001) with the OS. The median OS and the 5-year survival rate of patients treated with curative surgery (n=19) were 9.6 years and 65%, respectively, and of the conservatively treated patients, 0.7 years and 0% (n=14). Re-irradiation was delivered to nine patients, and radiation toxicity was observed in five patients. Conclusion In this study, RIS accounted for 0.9% of the cases of sarcoma, with increasing incidence. Despite the association of curative resection with increased survival, it could be applied to only 58% of the patients. Considering the limited treatment options for RIS, conduct of a genetic study to identify the underlying mechanism of RIS is needed.

Deformity of the proximal femur in fibrous dysplasia leads to deviation of the mechanical axis of the hip, which may lead to the development of secondary osteoarthritis (OA). This study investigated the prevalence and predisposing factors for the development of OA in patients with fibrous dysplasia of the proximal femur. We reviewed the records of 209 patients from our institutional database with fibrous dysplasia of the proximal femur, investigating possible predisposing factors including patient demographics, the extent of the coxa vara deformity, the presence of peri-articular disease, and the overall burden of skeletal disease. Of the 209 patients, 24 (12%) had radiological evidence of OA in the ipsilateral hip. The prevalence was significantly higher in patients with polyostotic fibrous dysplasia compared with those with monostotic disease (p < 0.001). In a subgroup analysis of patients with polyostotic disease, the extent of deformity (quantified using the neck–shaft angle), and the presence of peri-articular disease (whether in the head of the femur or the acetabulum) were significant predictors of osteoarthritis (neck–shaft angle likelihood ratio (LR) = 0.847 per 1° increase, p = 0.004; presence of lesion in the head of the femur LR = 9.947, p = 0.027; presence of lesion in the acetabulum LR = 11.231, p = 0.014). Our data suggest that patients with polyostotic fibrous dysplasia have a high risk of developing secondary OA of the hips. This risk is higher in patients with peri-articular disease, and those with a more severe deformity of proximal femur. Cite this article: Bone Joint J 2015;97-B:1007–11.