Reliability and accuracy of the critical shoulder angle measured by anteroposterior radiographs: using digitally reconstructed radiograph from 3-dimensional computed tomography images.

BACKGROUND: Accuracy of current standard radiographic measurement of the critical shoulder angle (CSA) is not well established. This study analyzed the reliability and accuracy of the CSA measurements obtained via anteroposterior (AP) radiographs, using a digitally reconstructed radiograph (true AP view) generated from a computed tomography image as the gold standard. METHODS: The CSA was measured on the radiographs and true AP views of 88 consecutive patients who had undergone shoulder arthroscopy for rotator cuff tears. Intraobserver and interobserver reliabilities of the CSA, measured by 2 orthopedic surgeons, were evaluated, and the average deviation of the CSA between radiographs and true AP views was calculated. Moreover, we compared the deviation of CSA between standard AP films (types A1 and C1) and nonstandard AP films (other types) against the Suter-Henninger criteria. RESULTS: Intraobserver and interobserver reliabilities were almost perfect on radiographs (0.96, 0.86) and true AP views (0.93, 0.85). The average deviation of CSA was 2.1° ± 1.6° for observer 1 and 2.2° ± 1.9° for observer 2. The percentage of cases with deviations of 2° or more when compared with the true AP view was 42% (37 of 88) for observer 1 and 53% (47 of 88) for observer 2. Only 22% (19 of 88) of films were standard AP films. The average deviation of CSA was not significantly different between standard and nonstandard AP films for observer 1 (standard 1.9° ± 1.3°; nonstandard 2.1° ± 1.7°; P = .76) and observer 2 (standard 1.6° ± 1.5°; nonstandard 2.4° ± 1.9°; P = .09). CONCLUSION: The CSA measurements using radiography were highly congruent, but a large measurement deviation occurred between radiographs and true AP views. The clinical usefulness and role of CSA in diagnosis require careful consideration.

Diagnostic accuracy of magnetic resonance imaging for partial tears of the long head of the biceps tendon in patients with rotator cuff tears.

Background: Magnetic resonance imaging (MRI) is useful for diagnosing shoulder diseases preoperatively. However, detection of partial tears of the long head of the biceps tendon (LHBT) using current clinical tests and imaging modalities is difficult. We aimed to evaluate the accuracy of radial-slice MRI for diagnosing partial tears of the LHBT. We hypothesized that radial-slice MRI may be a valuable diagnostic tool for assessing diagnosing tears of the LHBT. Methods: We retrospectively investigated 118 patients who underwent shoulder arthroscopy for rotator cuff tears. Intraoperative LHBT findings were compared with the identification of partial tears of the LHBT on conventional-slice MRI and radial-slice MRI, using a 3.0-T system. We calculated sensitivity, specificity, accuracy, and positive and negative predictive values for the detection of LHBT tears. Inter- and intraobserver reliability for radial-slice MRI was calculated using kappa statistics. Results: We diagnosed 69 patients (58%) without any LHBT tears and 49 with partial tears (42%), arthroscopically. Sensitivity, specificity, accuracy, and positive and negative predictive values of conventional-slice MRI for detection of partial tears of the LHBT were 52%, 94%, 78%, 92%, and 58%, respectively. Radial-slice MRI had 84% sensitivity, 90% specificity, 86% accuracy, and 92% positive and 80% negative predictive values for partial tears of the LHBT. Inter- and intraobserver reliability for radial-slice MRI was 0.69 and 0.74, respectively, corresponding to high reproducibility and defined as good. Conclusion: Radial-slice MRI demonstrated significantly higher sensitivity than conventional-slice MRI. These results indicate that radial-slice MRI is useful for diagnosing LHBT partial tears.

Relationship between preoperative size of rotator cuff tears measured using radial-slice magnetic resonance images and postoperative rotator cuff integrity: a prospective case-control study.

BACKGROUND: Magnetic resonance imaging (MRI) is useful for diagnosing shoulder diseases preoperatively. However, preoperative risk factors for retears have not been previously reported using a radial-slice MRI. Here, we investigated the relationship between the preoperative tear area of the rotator cuff evaluated using radial-slice MRI and the postoperative rotator cuff integrity. Our hypothesis is that larger tear area of the rotator cuff measured using radial-slice MRI would be associated with increased retear rates. METHODS: From June 2010 to October 2015, we treated 102 consecutive patients who underwent shoulder arthroscopy for reparable rotator cuff tears. The patient demographics, medical comorbidities, radiologic factors, tear size, fatty infiltration, muscle atrophy measured using oblique coronal and oblique sagittal MRI, and the tear area calculated using radial-slice MRI were assessed to compare the intact and retear groups in univariate and multivariate logistic regression analyses. The cutoff values of the independent factors were obtained using the receiver operating characteristic curve. RESULTS: Retears occurred in 15 of 102 (14.7%) patients. In the univariate analysis, significant differences were found between the two groups for tear size, fatty infiltration of the supraspinatus and infraspinatus, muscle atrophy, and tear area. In the multivariate analysis, the tear area was the independent factor that significantly affected the rate of retear. A tear area of 6.3 cm2 was the strongest predictor of retear with an area under the curve of 0.965, sensitivity of 86.7%, and specificity of 96.6%. CONCLUSION: The tear area was the independent factor that most significantly affected the rate of retear and showed excellent accuracy with a cutoff value of 6.3 cm2. Radial-slice MRI may be a valuable diagnostic tool for assessing the postoperative rotator cuff integrity.

Comparing in vivo three-dimensional shoulder elevation kinematics between standing and supine postures.

BACKGROUND: It is often assumed that body posture, standing vs. supine, changes shoulder muscle activation and range of motion, but these altered shoulder mechanics have not been objectively assessed. We expected the supine posture might facilitate scapular rotation and change subacromial pressure. The purpose of this study is to evaluate the influence of body posture on shoulder kinematics during arm elevation. METHODS: Ten males and eight females with a mean age of 33 years participated in this study. Shoulder kinematics were assessed during scapular plane elevation in the standing and supine postures by using single-plane fluoroscopic images. Kinematics were measured using 3-dimensional to 2-dimensional model-image registration techniques: matching the 3-dimensional bone model derived from computed tomography onto each fluoroscopic image. Glenohumeral superior/inferior translation, acromiohumeral distance, and scapular rotations were compared between the postures. The effect of sex also was evaluated. RESULTS: With the arm at the side position, the humeral head in the supine posture was located 0.5 mm superior compared to the standing posture (P < .001). During humeral elevation, the humeral head significantly shifted more inferiorly in the supine posture than in standing; the biggest mean difference was 0.6 mm, P = .003. But acromiohumeral distance during elevation was not significantly affected by the body posture (P = .05). Scapular upward rotation and posterior tilt were significantly different between the postures (P < .001). Sex had statistically significant, but quantitatively small, effects on shoulder kinematics. CONCLUSIONS: Body postures affect shoulder kinematics during humeral elevation. This knowledge will be useful to optimize rehabilitation exercises and for diagnostic insight.

Peptide vaccinations elicited strong immune responses that were reboosted by anti-PD1 therapy in a patient with myxofibrosarcoma.

Peptide-based immunotherapy does not usually elicit strong immunological and clinical responses in patients with end-stage cancer, including sarcoma. Here we report a myxofibrosarcoma patient who showed a strong clinical response to peptide vaccinations and whose immune responses were reboosted by anti-PD1 therapy combined with peptide vaccinations. The 46-year-old man showed a strong response to the peptide vaccinations (papillomavirus binding factor peptide, survivin-2B peptide, incomplete Freund's adjuvant, and polyethylene glycol-conjugated interferon-alpha 2a) and subsequent wide necrosis and massive infiltration of CD8+ T cells in a recurrent tumor. The patient's immune responses weakened after surgical resection; however, they were reboosted following the administration of nivolumab combined with peptide vaccinations. Thus, anti-PD1 therapy combined with peptide vaccinations might be beneficial, as suggested by the observations in this sarcoma patient.

Osteosarcoma-initiating cells show high aerobic glycolysis and attenuation of oxidative phosphorylation mediated by LIN28B.

Osteosarcoma (OS) is a highly malignant bone tumor and the prognosis for non-responders to chemotherapy remains poor. Previous studies have shown that human sarcomas contain sarcoma-initiating cells (SIC), which have the characteristics of high tumorigenesis and resistance to chemotherapy. In the present study, we characterized SIC of a novel OS cell line, screened for SIC-related genes, and tried to regulate the proliferation of OS by metabolic interference. Initially, we established a new human OS cell line (OS13) and isolated clones showing higher tumorigenesis as SIC (OSHIGH ) and counterpart clones. OSHIGH cells showed chemoresistance and their metabolism highly depended on aerobic glycolysis and suppressed oxidative phosphorylation. Using RNA-sequencing, we identified LIN28B as a SIC-related gene highly expressed in OSHIGH cells. mRNA of LIN28B was expressed in sarcoma cell lines including OS13, but its expression was not detectable in normal organs other than the testis and placenta. LIN28B protein was also detected in various sarcoma tissues. Knockdown of LIN28B in OS13 cells reduced tumorigenesis, decreased chemoresistance, and reversed oxidative phosphorylation function. Combination therapy consisting of a glycolysis inhibitor and low-dose chemotherapy had antitumor effects. In conclusion, manipulation of glycolysis combined with chemotherapy might be a good adjuvant treatment for OS. Development of immunotherapy targeting LIN28B, a so-called cancer/testis antigen, might be a good approach.

Implication of chemo-resistant memory T cells for immune surveillance in patients with sarcoma receiving chemotherapy.

Chemotherapy has improved the prognosis of patients with sarcomas. However, it may suppress anti-tumor immunity. Recently, we reported a novel CD8+ memory T cell population with a chemo-resistance property, "young memory" T (TYM ) cells. In this study, we investigated the proportion and function of TYM cells in peripheral blood of healthy donors and sarcoma patients who received chemotherapy and those who did not. The proportion of TYM cells was significantly decreased in patients compared with that in healthy donors. In healthy donors, anti-EBV CTLs were induced using mixed lymphocyte peptide culture, from not only TYM cells but also TCM and TEM cells. No CTLs directed to tumor-associated antigens were induced. In sarcoma patients who did not receive chemotherapy, in addition to anti-EBV CTLs, CTLs directed to the tumor-associated antigen PBF were induced from TYM , TCM and TEM cells. In sarcoma patients who received chemotherapy, EBV-specific CTLs were induced from TYM cells but were hardly induced from TEM cells. Interestingly, CTLs directed to the anti-tumor-associated antigen PBF were induced from TYM cells but not from the TCM and TEM cells in sarcoma patients who received chemotherapy. The findings suggest that TYM cells are resistant to chemotherapy and can firstly recover from the nadir. TYM cells might be important for immunological memory, especially in sarcoma patients receiving chemotherapy.

Identification of a novel human memory T-cell population with the characteristics of stem-like chemo-resistance.

High-dose chemotherapy may kill not only tumor cells but also immunocytes, and frequently induces severe lymphocytopenia. On the other hand, patients who recover from the nadir maintain immunity against infection, suggesting the existence of an unknown memory T-cell population with stress resistance, long-living capacity, proliferation and differentiation. Recently, the differentiation system of T-cell memory has been clarified using mouse models. However, the human T-cell memory system has great diversity induced by natural antigens derived from many pathogens and tumor cells throughout life, and profoundly differs from the mouse memory system constructed using artificial antigens and transgenic T cells. Here we report a novel human T-cell memory population, "young memory" T (TYM) cells. TYM cells are defined by positive expression of CD73, which represents high aldehyde dehydrogenase 1 (ALDH1) activity and CXCR3 among CD8(+)CD45RA(+)CD62L(+) T cells. TYM proliferate upon TCR stimulation, with differentiation capacity into TCM and TEM and drug resistance. Moreover, TYM are involved in memory function for viral and tumor-associated antigens in healthy donors and cancer patients, respectively. Regulation of TYM might be very attractive for peptide vaccination, adoptive cell-transfer therapy and hematopoietic stem cell transplantation.

The future of immunotherapy for sarcoma.

INTRODUCTION: The use of immunotherapeutic challenges for sarcoma has a long history. Despite the existence of objective responses, immunotherapy has been overshadowed by the results of chemotherapy, especially for osteosarcoma. However, the prognosis for non-responders to chemotherapy is still poor and immunotherapy is now focused on again. AREAS COVERED: We reviewed the following types of clinical trials of immunotherapy for sarcoma: (i) vaccination with autologous tumor cells, (ii) vaccination with peptides derived from tumor-associated antigens, (iii) adoptive cell transfer using engineered T cells expressing T cell receptor directed at NY-ESO-1 and (iv) immune checkpoint inhibitors targeting CTLA-4 and PD1/PDL1. EXPERT OPINION: The immunogenicity of sarcoma might be lower than that of melanoma. Patients with small lesions who have not received any chemotherapy are good candidates for peptide-based immunotherapy. Combining peptide vaccination and immune checkpoint inhibitors is an attractive option, and long-lived memory T cells are attracting attention. Memory T stem cells defined by CD95+ are long-lived and have the capacity for self-renewal and multidifferentiation. We also identified a novel memory T cell population, young memory T cells defined by CD73+CXCR3+. Regulation of such memory T stem cells will be useful for peptide vaccination and adoptive cell transfer.