Search

This document is an editorial from the International Journal of Molecular Sciences titled "Pathology, Diagnosis, and Management of Sarcoma." The editorial discusses the challenges in investigating sarcoma due to its rarity and heterogeneity. It highlights recent advancements in understanding the molecular pathogenesis of sarcomas, including molecular genetic techniques and immunohistochemical markers. The editorial also presents research on specific types of sarcomas, such as osteosarcoma and Ewing's sarcoma, and explores potential therapeutic approaches for soft tissue sarcomas. Additionally, it discusses targeted protein degradation as a promising pharmacological modality for sarcoma treatment. Overall, the editorial provides valuable insights into the current understanding and management of sarcomas. [Extracted from the article]

Surgery for bone metastasis has two primary goals—palliative care to relieve pain, instability and paralysis, and tumor resection for curing the disease. Oncologically en bloc resection, followed by a reconstruction of the bone defect is the treatment of choice in single bone metastasis from renal cell carcinoma or thyroid cancer. Bone metastases may occur in the extremities, pelvis, or spine, and different resection and reconstruction methods depend on the regional anatomy. For instance, multiple options are available for reconstruction of the pelvis, especially for the acetabulum, including anatomical reconstruction using custom-made implants or recycled autologous bone grafting when a long-term prognosis is expected. Recently, for the spine, total en bloc spondylectomy is extensively performed despite the initial limitations of surgical invasiveness, such as blood loss. Principally, palliative surgery aims to maintain lasting bony stability with minimal surgical invasiveness. Intramedullary nails and plate fixation are frequently used in the extremities but the postoperative failure rate is relatively high. Therefore, surgeons should consider the use of long intramedullary nails and long-type stems for endoprosthesis reconstruction along with cement fixation to reduce the failure rate. Although short-term complications, such as dislocation, have been observed with endoprosthesis reconstruction, it is stable in the long-term follow-up. Percutaneous bone cement injection into the spine and pelvis is also effective and less invasive. [ABSTRACT FROM AUTHOR]

• ICIs are beneficial for NSCLC with bone metastases. • Serum inflammatory and nutritional indicator dynamics may predict response to ICIs. • We developed a novel predictive scoring system based on these indicators. • This scoring system is a non-invasive technique with high predictive accuracy. We aimed to investigate the association of the dynamics of serum inflammatory and nutritional indicators with immune checkpoint inhibitor (ICI) response in non-small-cell lung cancer (NSCLC) with bone metastases, and to develop a novel predictive scoring system based on these indicators. Patients with NSCLC having bone metastases treated with ICIs were categorized as: the development cohort (January 2016 to March 2021, n = 60) and the validation cohort (April 2021 to June 2023, n = 40). Serum indicators of inflammation and nutrition such as C-reactive protein (CRP), neutrophil-to-lymphocyte ratio (NLR), albumin, prognostic nutritional index (PNI) were investigated before and six weeks after ICI initiation. The correlations of these dynamics with bone metastasis response rate (BoMRR) and overall survival (OS) were analyzed. A scoring system consisting of independent predictors was developed (IMMUNO-SCORE) and correlations with clinical outcomes were validated using the validation cohort. In the development cohort, multivariable analysis showed that NLR and PNI dynamics and CRP, NLR, and PNI dynamics were independent predictors of BoMRR and OS, respectively. The IMMUNO-SCORE consisting of NLR and PNI dynamics, which were the common predictors of the clinical outcomes, was significantly correlated with BoMRR (p < 0.01) and OS (p < 0.001) in cross-validation. The area under the curve of the score (0.786) was higher than individual NLR and PNI dynamics (0.72 and 0.684). Dynamics in NLR and PNI were demonstrated as biomarkers of treatment response and prognosis in ICI treatment of NSCLC with bone metastases, and the score combining these biomarkers was significantly correlated with clinical outcomes. [ABSTRACT FROM AUTHOR]

Camurati-Engelmann disease (CED) is a rare, progressive diaphyseal dysplasia characterized as diaphyseal hyperostosis and sclerosis of the long bones. Corticosteroids, bisphosphonates, and losartan have been reported to be effective systemic medications used to reduce CED symptoms. There are no reports of osteoblastoma in patients with CED, and osteoblastoma in the distal radius is rare. We present a patient diagnosed with CED, based on radiological and histological examinations, at 11 years old. At 22 years old, she experienced severe pain in her right forearm and was treated with bisphosphonate, losartan, and prednisolone; however, the pain continued. An expansive and sclerotic lesion at the distal radius was observed on radiography. A follow-up plain radiograph indicated that the lesion was growing. Fluorodeoxyglucose positron emission tomography revealed solitary, intense radiotracer uptake, and a biopsy and surgical resection were performed due to suspected malignancy. Pathologic analysis showed anastomosing bony trabeculae rimmed by osteoblasts observed in a loose fibrovascular stroma. The lesion was diagnosed as an osteoblastoma. Following bone excision and artificial bone grafting, the patient's severe pain almost completely disappeared. At final follow-up, no evidence of osteoblastoma recurrence was noted. To our knowledge, this is the first case report of osteoblastoma arising in a patient with CED. Bone excision and artificial bone grafting may be a treatment option for local symptomatic osteoblastoma in patients with CED. [ABSTRACT FROM AUTHOR]

Background: Soft-tissue metastasis of carcinoma is rare. In the present study, we investigated the surgical indications and clinical features of patients with soft tissue metastases of carcinoma. Methods: In this retrospective cohort study, we enrolled 26 patients with soft tissue carcinoma metastasis referred to our department for treatment. Sex, age, location, size, depth, pain due to the tumor, primary origin, serum C-reactive protein (CRP) level, MRI examinations, diagnosis by a previous physician, carcinoma markers from blood, history of carcinoma, other metastases, performance status (PS), and surgical procedures were documented. Associations between variables and surgery were statistically analyzed. Results: The primary cancer origin was found to be the lung (n = 10), kidney (n = 7), esophagus (n = 2), stomach (n = 1), breast (n = 1), liver (n = 1), ureter (n = 1), anus (n = 1), and unknown (n = 2). The mean CRP level of all patients was 2.3 mg/dL. Seven tumors (26.9%) were originally suspected to be soft tissue metastases of carcinoma, while 19 tumors (73.1%) were considered soft tissue sarcomas or inflammatory lesions by the previous treating physician. Twenty patients (76.9%) had other metastases. The PS of the 12 patients (46.2%) was zero. Eleven patients (42.3%) underwent surgery for soft tissue metastases. Diagnosis of soft tissue metastasis by a previous physician and good PS (p < 0.05) were significantly associated with surgery. Conclusion: Overall, the present results show that surgical indications for soft tissue metastasis of carcinoma include diagnosis by the referring physician or good PS of the patients. [ABSTRACT FROM AUTHOR]

We report on a study of the high-mass star formation in the H  ii region W 28 A2 by investigating the molecular clouds that extend over ∼5–10 pc from the exciting stars using the 12CO and 13CO (J = 1–0) and 12CO (J = 2–1) data taken by NANTEN2 and Mopra observations. These molecular clouds consist of three velocity components with CO intensity peaks at V LSR ∼ −4 km s−1, 9 km s−1, and 16 km s−1. The highest CO intensity is detected at V LSR ∼ 9 km s−1, where the high-mass stars with spectral types O6.5–B0.5 are embedded. We found bridging features connecting these clouds toward the directions of the exciting sources. Comparisons of the gas distributions with the radio continuum emission and 8 μm infrared emission show spatial coincidence/anti-coincidence, suggesting physical associations between the gas and the exciting sources. The 12CO J = 2–1 to 1–0 intensity ratio shows a high value (≳0.8) toward the exciting sources for the −4 km s−1 and +9 km s−1 clouds, possibly due to heating by the high-mass stars, whereas the intensity ratio at the CO intensity peak (V LSR ∼ 9 km s−1) decreases to ∼0.6, suggesting self absorption by the dense gas in the near side of the +9 km s−1 cloud. We found partly complementary gas distributions between the −4 km s−1 and +9 km s−1 clouds, and the −4 km s−1 and +16 km s−1 clouds. The exciting sources are located toward the overlapping region in the −4 km s−1 and +9 km s−1 clouds. Similar gas properties are found in the Galactic massive star clusters RCW 38 and NGC 6334, where an early stage of cloud collision to trigger the star formation is suggested. Based on these results, we discuss the possibility of the formation of high-mass stars in the W 28 A2 region being triggered by cloud–cloud collision. [ABSTRACT FROM AUTHOR]

Bone defect reconstruction with artificial materials may produce good functional recovery in the short term. Over time, the durability of artificial materials becomes an issue, and therefore, artificial materials cannot be considered a permanent solution to reconstruction. For long-term outcomes, the goal is to regain function, permanence, and form that are as close to normal as possible. Thus, physiological materials are desirable for use in reconstruction. Biological reconstruction involves the use of materials that are modified in vivo following reconstruction of bone defects. The goal is to achieve bone union, bone revival and remodeling, with biointegration of soft tissue and bone. Allograft use has been the mainstay of bone defect reconstruction in most parts of the world, although in some countries like Japan, allogeneic bone is difficult to obtain due to socio-religious concerns. Therefore, we developed new biological reconstruction techniques to overcome this problem. Bone derived from distraction osteogenesis is autologous bone, which must be an ideal reconstruction material for its biological affinity, strength, resilience, and immunity to infection. When applying this method to patients with malignant disease however, it is important to preserve as much of the local soft tissue as possible, and the clinician must be especially careful of infection and callus formation. Liquid nitrogen treatment of tumor-bearing bone produces equal, if not better, bone revitalization compared to other forms of treatment to date. Reconstruction with liquid nitrogen-treated bone involves resecting the diseased bone and returning it to the body following liquid nitrogen treatment (free-freezing method). Another method involves dislocating the joint proximal to the tumor, or cutting the bone while the distal side remains attached to the body and the limb inverted and treated with liquid nitrogen (pedicle freezing method). When both methods are possible, the pedicle freezing method is preferable since it is performed with minimal osteotomy. Our recent research has looked into the possible role of adipose-derived stem cells in promoting bone fusion and revitalization. This method has produced promising results for the future of biological reconstruction. [ABSTRACT FROM AUTHOR]

Simple Summary: In this retrospective cohort study, predictive factors for graft survival were investigated in 123 patients who underwent reconstructions using a tumor-bearing frozen autograft after bone tumor resection of the extremities. The graft survival rates were 83.2% at 5 years and 70.2% at 10 years. Multivariate analysis using the Cox proportional hazards regression model revealed that BMI of ≥23.6 (HR, 3.4; p = 0.005), tibia (HR, 2.3; p = 0.047), and freezing procedure (HR, 0.3; p = 0.016) were independently associated with graft survival. Based on the results, pedicle or hemicortical freezing techniques are recommended in cases where these techniques can be applied. Tumor-bearing frozen autografts have been widely used for reconstruction of bone defects caused by tumor resection. However, some patients undergo removal of the grafted bone due to surgical site infection, tumor recurrence, or fractures of the grafted bone. In this retrospective cohort study, predictive factors for graft survival were investigated in 123 patients who underwent reconstructions using a tumor-bearing frozen autograft after bone tumor resection of the extremities. To determine the independent predictors of graft survival, the association between various parameters and graft survival was investigated. The graft survival rates were 83.2% at 5 years and 70.2% at 10 years. Among the 123 frozen autografts, 25 (20.3%) were removed because of complications. In univariate analyses, male sex, BMI of ≥23.6, tibia, and chemotherapy were significantly associated with poor graft survival, whereas the pedicle/hemicortical freezing procedure was significantly associated with better graft survival. Multivariate analysis using the Cox proportional hazards regression model revealed that BMI of ≥23.6 (HR, 3.4; p = 0.005), tibia (HR, 2.3; p = 0.047), and freezing procedure (HR, 0.3; p = 0.016) were independently associated with graft survival. Based on the results, pedicle or hemicortical freezing techniques are recommended in cases where these techniques can be applied. [ABSTRACT FROM AUTHOR]

Adipose-derived stem cells (ADSCs) have been studied for many years as a therapeutic option for osteoarthritis (OA); however, their efficacy remains insufficient. Since platelet-rich plasma (PRP) induces chondrogenic differentiation in ADSCs and the formation of a sheet structure by ascorbic acid can increase the number of viable cells, we hypothesized that the injection of chondrogenic cell sheets combined with the effects of PRP and ascorbic acid may hinder the progression of OA. The effects of induction of differentiation by PRP and formation of sheet structure by ascorbic acid on changes in chondrocyte markers (collagen II, aggrecan, Sox9) in ADSCs were evaluated. Changes in mucopolysaccharide and VEGF-A secretion from cells injected intra-articularly in a rabbit OA model were also evaluated. ADSCs treated by PRP strongly chondrocyte markers, including type II collagen, Sox9, and aggrecan, and their gene expression was maintained even after sheet-like structure formation induced by ascorbic acid. In this rabbit OA model study, the inhibition of OA progression by intra-articular injection was improved by inducing chondrocyte differentiation with PRP and sheet structure formation with ascorbic acid in ADSCs. [ABSTRACT FROM AUTHOR]

Background: Low-grade osteosarcoma, including low-grade central osteosarcoma and parosteal osteosarcoma, is an extremely rare variant, and the diagnosis is occasionally difficult. In this article we present cases of low-grade osteosarcomas that should be reviewed by a clinical oncologist. Patients and methods: Nine cases of histologically diagnosed Broder grade 1 osteosarcoma were retrospectively reviewed. The pathological diagnoses included parosteal osteosarcoma, low-grade central osteosarcoma, and low-grade chondroblastic osteosarcoma in four, four, and one cases, respectively. Results: Duration from initial surgical intervention including biopsy to final diagnosis as low-grade osteosarcoma was a mean of 9.4 months. The initial benign diagnoses on biopsy specimens included fibrous dysplasia in three cases, chondroblastoma in one case, and a giant cell tumor in one case. The average number of histological examinations was 1.8. Low-grade osteosarcomas are well suited for biological reconstruction: seven cases were reconstructed by frozen autografts, distraction osteogenesis, or vascularized bone grafts. Conclusion: Low-grade osteosarcomas can be misdiagnosed as benign lesions, especially fibrous dysplasia. If the diagnosis of a low-grade osteosarcoma is not established on the basis of radiologic findings, care should be exercised, even when a biopsy suggests a benign lesion. Low-grade osteosarcomas should be treated with wide excision, even after an intralesional excision. Biological reconstruction might be a better option for low-grade osteosarcomas. [ABSTRACT FROM AUTHOR]

Background: Scapulectomy requires not only joint resection but also wide resection of the shoulder girdle muscles. Even the significance of reconstruction has not yet been determined because of the difficulties in comparing the different conditions. The purpose of this study was to investigate factors that influence functional outcomes after scapulectomy in a multicenter study. Methods: This retrospective study comprised 48 patients who underwent total or subtotal scapulectomy and were followed for at least one year after surgery. Patients were registered at the Japanese Musculoskeletal Oncology Group affiliated hospitals. Soft tissue reconstruction for joint stabilization was performed when there was enough remaining tissue for reconstruction of the rotator cuff and tendons. In 23 cases, humeral suspension was performed. The average follow-up period was 61.9 months. Multivariate analysis was performed using the patient’s background to determine which factors influence the Enneking functional score or active range of motion. Results: The average functional score was 21.1 out of 30. Active shoulder range of motion was 42.7 degree in flexion, 39.7 degree in abduction, 49.6 degree of internal rotation and 16.8 degree of external rotation. The amount of remaining bone influenced functional outcome, which means that preserving the glenoid or the acromion lead to better function compared to total scapulectomy (p<0.01). Factors that influenced each functional measure include the amount of remaining bone, soft tissue reconstruction, the length of the resected humerus and nerve resection (p<0.05). Conclusion: Although shoulder function was almost eliminated following total or subtotal scapulectomy, minimal resection of bone, and soft tissue reconstruction should lead to better function. [ABSTRACT FROM AUTHOR]

Abstract: Hard X-ray Imager (HXI) and Soft Gamma-ray Detector (SGD) onboard the 6th Japanese X-ray satellite, ASTRO–H, utilize double-sided silicon strip detectors (DSSD) and pixel array-type silicon sensors (Si-pad), respectively. The DSSD with a 3.4cm×3.4cm area has an imaging capability in the lower energy band for the HXI covering 5–80keV. The Si-pad consists of 16×16 pixels with a 5.4cm×5.4cm area and measures a photon direction with the Compton kinematics in 10–600keV. Since the ASTRO–H will be operated in a low earth orbit, these detectors will be damaged by irradiation of cosmic-ray protons mainly in the South Atlantic Anomaly. In order to evaluate damage effects of the sensors, we have carried out irradiation tests with 150MeV proton beams and 60Co gamma-rays with a total dose of 10–20 years irradiation level. In both experiments, the leakage current has increased by under an expected operation temperature at −15°C, which resulted in the noise level within a tolerance of 20 years. In this report, we present a summary of the basic performance of silicon detectors, and radiation effects on them by the irradiation tests. [Copyright &y& Elsevier]

Background. We report a retrospective case series analysis of clinical outcomes of patients with soft tissue sarcoma around the elbow. Methods. Twenty-two patients underwent surgical tumor excision between January 1999 and May 2017, with a mean follow-up of 85.2 months. Results. Six tumors were localized in the upper arm, nine in the elbow, and seven in the forearm. Sixteen tumors were deep-seated, and six were superficially located. Fifteen patients underwent wide excision, including one amputation, and 18 achieved (81.8%) negative margins histologically. Two local recurrences and four distant metastases developed. The mean Musculoskeletal Tumor Society score was 92.0% (range, 33.3–100). The 5-year local recurrence-free survival rate, metastasis-free survival rate, and overall survival rate were 90.0%, 77.0%, and 79.7%, respectively. Conclusions. Local control and limb function can have favorable outcomes when the tumor excised has a histologically negative margin without sacrificing the major structure. [ABSTRACT FROM AUTHOR]

Background: Under most circumstances, the resection of soft tissue sarcomas of the extremities can be limb-sparing, function-preserving oncologic resections with adequate margins. However, en bloc resection may require resection of the major peripheral nerves, causing poor function in the extremities. Although liquid nitrogen treatment has been used to sterilize malignant bone tumors, its use in the preparation of nerve grafts has, to our knowledge, not been reported. Hence, this study aimed to investigate the tumor recurrence and function after peripheral nerve reconstruction using liquid nitrogen–treated tumor-bearing nerves in a rat model. Questions/purposes: (1) Do liquid nitrogen–treated frozen autografts have regeneration capabilities? (2) Do liquid nitrogen–treated tumor-bearing nerves cause any local recurrences in vivo in a rat model? Methods: Experiment 1: Twelve-week-old female Wistar rats, each weighing 250 g to 300 g, were used. A 10-mm-long section of the right sciatic nerve was excised; the prepared nerve grafts were bridge-grafted through end-to-end suturing. The rats were grouped as follows: an autograft group, which underwent placement of a resected sciatic nerve after it was sutured in the reverse orientation, and a frozen autograft group, which underwent bridging of the nerve gap using a frozen autograft. The autograft was frozen in liquid nitrogen, thawed at room temperature, and then thawed in distilled water before application. The third group was a resection group in which the nerve gap was not reconstructed. Twenty-four rats were included in each group, and six rats per group were evaluated at 4, 12, 24, and 48 weeks postoperatively. To assess nerve regeneration after reconstruction using the frozen nerve graft in the nontumor rat model, we evaluated the sciatic functional index, tibialis anterior muscle wet weight ratio, electrophysiologic parameters (amplitude and latency), muscle fiber size (determined with Masson trichrome staining), lower limb muscle volume, and immunohistochemical findings (though neurofilament staining and S100 protein produced solely and uniformly by Schwann cells associated with axons). Lower limb muscle volume was calculated via CT before surgery (0 weeks) and at 4, 8, 12, 16, 20, 24, 32, 40, and 48 weeks after surgery. Experiment 2: Ten-week-old female nude rats (F344/NJcl-rnu/rnu rats), each weighing 100 g to 150 g, were injected with HT1080 (human fibrosarcoma) cells near the bilateral sciatic nerves. Two weeks after injection, the tumor grew to a 10-mm-diameter mass involving the sciatic nerves. Subsequently, the tumor was resected with the sciatic nerves, and tumor-bearing sciatic nerves were obtained. After liquid nitrogen treatment, the frozen tumor-bearing nerve graft was trimmed to a 5-mm-long tissue and implanted into another F344/NJcl-rnu/rnu rat, in which a 5-mm-long section of the sciatic nerve was resected to create a nerve gap. Experiment 2 was performed with 12 rats; six rats were evaluated at 24 and 48 weeks postoperatively. To assess nerve regeneration and tumor recurrence after nerve reconstruction using frozen tumor-bearing nerve grafts obtained from the nude rat with human fibrosarcoma involving the sciatic nerve, the sciatic nerve's function and histologic findings were evaluated in the same way as in Experiment 1. Results: Experiment 1: The lower limb muscle volume decreased once at 4 weeks in the autograft and frozen autograft groups and gradually increased thereafter. The tibialis anterior muscle wet weight ratio, sciatic functional index, muscle fiber size, and electrophysiologic evaluation showed higher nerve regeneration potential in the autograft and frozen autograft groups than in the resection group. The median S100-positive areas (interquartile range [IQR]) in the autograft group were larger than those in the frozen autograft group at 12 weeks (0.83 [IQR 0.78 to 0.88] versus 0.57 [IQR 0.53 to 0.61], difference of medians 0.26; p = 0.04) and at 48 weeks (0.86 [IQR 0.83 to 0.99] versus 0.74 [IQR 0.69 to 0.81], difference of median 0.12; p = 0.03). Experiment 2: Lower limb muscle volume decreased at 4 weeks and gradually increased thereafter. The median muscle fiber size increased from 0.89 (IQR 0.75 to 0.90) at 24 weeks to 1.20 (IQR 1.08 to 1.34) at 48 weeks (difference of median 0.31; p< 0.01). The median amplitude increased from 0.60 (IQR 0.56 to 0.67) at 24 weeks to 0.81 (IQR 0.76 to 0.90) at 48 weeks (difference of median 0.21; p < 0.01). Despite tumor involvement and freezing treatment, tumor-bearing frozen grafts demonstrated nerve regeneration activity, with no local recurrence observed at 48 weeks postoperatively in nude rats. Conclusion: Tumor-bearing frozen nerve grafts demonstrated nerve regeneration activity, and there was no tumor recurrence in rats in vivo. Clinical Relevance: A frozen nerve autograft has a similar regenerative potential to that of a nerve autograft. Although the findings in a rat model do not guarantee efficacy in humans, if they are substantiated by large-animal models, clinical trials will be needed to evaluate the efficacy of tumor-bearing frozen nerve grafts in humans. [ABSTRACT FROM AUTHOR]

Background: The supra-acetabulum is a common site for malignant bone tumors, which can be difficult to differentiate from insufficiency fractures. We report a rare case of a stress fracture of the supra-acetabulum that required differentiation from a malignant bone tumor.Case Presentation: A 74-year-old Japanese man presented to the hospital because of right hip joint pain. X-rays showed no obvious abnormalities. Magnetic resonance imaging showed an abnormality in the right supra-acetabulum, and he was referred to our department. A linear, low-signal region and its surrounding equal signal region were observed at the same site in the T1-weighted image, and a linear low-signal region and high signal region were observed in the surrounding area in the T2-weighted image. On the contrast-enhanced magnetic resonance imaging, the lesion was still unclear and the whole area was gradually enhanced. A computed tomography-guided needle biopsy was performed, but no tumor cells were observed, therefore the lesion was presumed to be a fracture healing. The bone density was 66% for the lumbar spine (young adult mean, L2-4), and blood biochemistry showed an increase in alkaline phosphatase and total type I procollagen N-terminal propeptide.Conclusion: This case was diagnosed as an insufficiency fracture of the supra-acetabulum in a male patient with primary osteoporosis by biopsy specimen. Initially, a pathological fracture associated with a malignant lesion was considered. On magnetic resonance imaging, the boundary around the fracture line was unclear and a signal change that was gradually enhanced by gadolinium was observed. This is likely to be bone marrow edema associated with the stress fracture, and we believe this to be a useful finding that may help in differentiating a stress fracture from a pathological fracture secondary to a malignant lesion. [ABSTRACT FROM AUTHOR]

Background: The shoulder girdle is a common site for malignant bone and soft tissue tumors. Total scapulectomy represents an attractive alternative to amputation when the whole scapula is invaded with tumor and the neurovascular bundle can be preserved during tumor resection. The purpose of this study was to investigate functional outcomes after total scapulectomy. Patients and methods: The study comprised seven patients, four of whom underwent soft tissue reconstruction for joint stabilization, including suture of the biceps tendon onto the clavicle or humeral head, reattachment of the rotator cuff, and/or humeral suspension. The remaining three patients did not undergo soft tissue reconstruction; instead, only the remaining muscles were sutured. Results: Mean Enneking functional score was 57%. Preservation of elbow, wrist and finger motion resulted in an acceptable level of postoperative limb function. No significant differences in function were observed between the soft tissue reconstruction group and the non-reconstruction group. Conclusion: Total scapulectomy is a feasible alternative to amputation as it preserves acceptable elbow and hand function. [ABSTRACT FROM AUTHOR]

The article focuses on the use of three-dimensional (3D) analysis on patients with thoracic apical sagittal alignment in adolescent idiopathic scoliosis. It aims to identify the differences between the standard lateral projection and true lateral view of the patient's thoracic sagittal alignment. A total of 66 adolescent patients with idiopathic scoliosis were subjected to biplanar radiographs. Findings reveal that 3D analysis is more accurate than the use of standard lateral radiographs.

Background: The lymphatic system is a major route for cancer cell dissemination, and a potential target for antitumor therapy. Despite ongoing interest in this area of research, the real-time behavior of cancer cells trafficking in the lymphatic system is poorly understood due to lack of appropriate tools to image this process. Materials and methods: We have used monoclonal-antibody and fluorescence technology to color-code lymphatic vessels and the cancer cells inside them in a living animal. Monoclonal anti-mouse LYVE-1 antibody was conjugated to a green fluorophore and delivered to the lymphatic system of a nude mouse, allowing imaging of mouse lymphatics. Tumor cells engineered to express red fluorescent protein were then imaged traveling within the labeled lymphatics in real time. Results: AlexaFluor-labeled monoclonal anti-mouse LYVE-1 created a durable signal with clear delineation of lymphatic architecture. The duration of fluorescent signal after conjugated LYVE-1 delivery was far superior to that of fluorescein isothiocyanate-dextran or control fluorophore-conjugated IgG. Tumor cells engineered to express red fluorescent protein delivered to the inguinal lymph node enabled real-time tracking of tumor cell movement within the green fluorescent-labeled lymphatic vessels. Conclusions: This technology offers a powerful tool for the in vivo study of real-time trafficking of tumor cells within lymphatic vessels, for the deposition of the tumor cells in lymph nodes, as well as for screening of potential antitumor lymphatic therapies. [Copyright &y& Elsevier]

Background: Angiogenesis is a critical step in tumor growth, progression, and metastasis. Soft tissue and bone sarcoma are resistant to most therapeutic approaches. Angiogenesis of these tumors may be an effective target. We hypothesized that we could inhibit tumor growth by targeting angiogenesis in a mouse model of sarcoma. We demonstrate in this report, using powerful color-coded fluorescent imageable tumor-host models, the onset of angiogenesis of these sarcomas and its inhibition. Materials and methods: Transgenic mice were used as the host in which green fluorescent protein (GFP) is driven by a regulatory element of the stem cell marker nestin (ND-GFP). Nascent blood vessels express ND-GFP in this model. We visualized, by dual-color fluorescence imaging, angiogenesis of sarcoma formed by the HT-1080 human fibrosarcoma cell line expressing red fluorescent protein (RFP) in the ND-GFP mice. Tumor cells were injected into either the muscle or the bone. Results: Nestin was highly expressed in proliferating endothelial cells and nascent blood vessels in the growing tumors, including the surrounding tissues. Immunohistochemical staining showed that CD31 colocalized in ND-GFP-expressing nascent blood vessels. The density of nascent blood vessels in the tumor was readily quantitated. The mice were given daily i.p. injections of 5 mg/kg of doxorubicin after implantation of tumor cells. Doxorubicin significantly decreased the mean nascent blood vessel density in the tumors as well as decreased tumor volume. Conclusion: The dual-color model of the ND-GFP nude mouse and RFP sarcoma cells is useful for the visualization and quantitation of bone and soft tissue tumor angiogenesis and evaluation of angiogenic inhibitors for such tumors. These data suggest targeting angiogenesis of sarcomas as a promising clinical approach. [Copyright &y& Elsevier]

Abstract: The natural course of hepatitis C virus (HCV) carriers is not well understood. We examined the clinical characteristics of individuals exhibiting spontaneous elimination of HCV as part of a cohort study of residents of a HCV hyperendemic area in Japan. In individuals who were judged to have persistent HCV infection in 1995, 302 had at least 4 annual ALT measurements between 1993 and 2000, and had not been treated with IFN. They were tested for the presence of HCV RNA in 2001 and/or 2002 and HCV RNA could not be detected in 20 of the 302 individuals. In these 20 individuals, 7 were confirmed to have detectable HCV RNA and 13 were not until 2000. Thus, 2.4% (7/289) were judged to have spontaneously eliminated the HCV infection during that 6-year period. Although there were no differences in age, sex, ALT levels, or serologically defined HCV genotype between individuals with and without exhibiting spontaneous elimination, there was a significant relationship between the elimination of HCV RNA and a low level of HCVcAg (<20pg/mL) (P < 0.001) upon testing in 1995. These results suggest that spontaneous elimination of HCV RNA following persistent infection is rare and appears to be related to viral load. [Copyright &y& Elsevier]

Inflammatory pseudotumor of the liver is a rare benign lesion, but exploratory laparotomy and a hepatectomy are often performed unnecessarily after various misdiagnoses, including liver abscess, hepatocellular carcinoma, metastatic liver tumor, and cholangiocarcinoma. We present a case of hepatic inflammatory pseudotumor in a 17-year-old man in whom diagnosis was confirmed by liver needle biopsy under ultrasonographic tomography (UST) guidance. He had complained of fever and right hypochondralgia 2 months after being operated for appendicitis. He was admitted to our hospital because of the persistence of these symptoms and the presence of a hepatic mass lesion detected by UST. He had hepatomegaly, with tenderness; leukocytosis and elevated erythrocyte sedimentation rate and C-reactive protein level were noted. UST showed a hypoechoic mass in the liver and pre-contrast computerized tomography (CT) revealed a low-density area with an ill defined margin, which was barely enhanced by the contrast medium. On the basis of the patient's clinical symptoms and the laboratory data and imaging studies, the presence of a liver abscess was suspected and antibiotics were administered. One month after the initiation of the antibiotic therapy, UST demonstrated that the portal vein had dilated serpiginously and penetrated into the mass. As the heterogeneous appearance displayed by post-enhanced CT indicated the need for a differential diagnosis of the hepatic mass lesion to rule out hepatocellular carcinoma, percutaneous needle biopsy was performed, under UST guidance. Histopathological examination demonstrated marked infiltration of plasma cells and fibrosis, findings which were consistent with those of hepatic inflammatory pseudotumor. There was a spontaneous reduction of the hepatic pseudotumor without continuous antibiotics and this reduction was documented on follow-up UST and CT. [ABSTRACT FROM AUTHOR]

Gait training to intentionally lengthen the nonparetic step length can increase the propulsive force of the paretic leg but may also induce overactivity of the knee extensor muscles that might limit knee flexion during the swing phase. Herein, we investigated the effects of lengthening the nonparetic step length during gait on the joint motion and muscle activity of the paretic lower limb. Fifteen chronic stroke patients (stroke group) and 15 healthy participants (control group) were evaluated for lower limb joint movements, electromyography, and spatiotemporal gait parameters during walking. Walking conditions were Normal (comfortable walking) and NP-Long/Contralateral-Long (walking with a lengthened step length of the nonmeasured limb). The trailing limb angle, a surrogate for propulsive forces, was increased in both groups by changing the step length, with no significant change in the peak knee flexion angle during the swing phase. However, the stroke group did not increase ankle plantar flexor activity in the stance phase or ankle dorsiflexion angle in the swing phase. Intentionally lengthening the nonparetic step length did not limit knee flexion. However, the effect of increased propulsive force during the stance phase was insufficient, with the possibility of decreased foot clearance. [ABSTRACT FROM AUTHOR]

Background: Recently, the T2 alpha nailing system (Stryker, Inc.), which has advanced locking screws that can attach a screw to a rod, has been used worldwide and is expected to improve fracture fixation. We analyzed two cases of supracondylar femoral fractures in older adult patients, in which intraoperative fractures occurred during the insertion of advanced locking screws of the T2 alpha femur retrograde intramedullary nail. Case presentation: A 93-year-old and an 82-year-old woman each underwent T2 alpha femur retrograde nail fixation for supracondylar femur fractures at separate hospitals, and advanced locking screws were used as the proximal transverse locking screws. In both patients, a fracture line was observed at the proximal screw postoperatively, and the fractures were refixed with distal cable wiring and/or femoral distal plates. The patients were subsequently discharged from the same facility with no remarkable pain. Conclusions: When inserting advanced locking screws, it is necessary to enlarge the screw hole in the near-bone cortex with a counterbore drill, which might add torque to the bone cortex that could result in fractures. If the sleeve is distant from the bone, the counterbore drill will not reach the bone, the screw hole will not expand, and the insertion of advanced locking screws will apply a strong torque to the bone cortex and may result in fracture. Moreover, it is important to confirm that the counterbore drill is securely inserted under fluoroscopy and to carefully enlarge the bony foramen manually to prevent fractures during screw insertion. [ABSTRACT FROM AUTHOR]

Epithelioid hemangioendothelioma (EHE) is a rare malignant vascular neoplasm that requires long-term management. Several reports describe disseminated intravascular coagulation (DIC) associated with angiosarcoma, but no association with EHE has been reported. We encountered a patient with DIC complicated by multifocal EHE. The patient was an 83-year-old woman with spinal lesions, small lung nodules, and a soft tissue mass in the right buttock. The tumor was biopsied and diagnosed as EHE. The patient received pain control therapy without antitumor therapy. One month later, DIC developed with tumor progression. DIC subsided with nafamostat mesylate infusion, and oral apixaban was administered. DIC was managed for 5 months until the patient died of brain metastases. This is the first report of a patient with DIC complicated by EHE. It should be noted that progression of EHE can cause DIC. We were able to manage DIC using anticoagulant agents. [ABSTRACT FROM AUTHOR]

Age affects the clinical outcomes of cancer treatment, including those for bone sarcoma. Successful reconstruction using frozen autograft after excision of bone sarcoma has been reported; however, little is known about the clinical outcomes of frozen autograft reconstruction according to age. The purpose was to evaluate the clinical outcomes of the frozen autograft reconstruction focusing on skeletally mature adolescents and young adults (AYAs) that was 15 to 39 years of age. A total of 37 AYA patients with primary bone sarcoma on the appendicular skeleton were enrolled in this study. The mean follow-up period was 89 months. The graft survival (GS), overall survival (OS), recurrence-free survival (RFS), complications and the function were retrospectively evaluated using medical records. The 10-year GS, OS, and RFS rates were 76%, 84%, and 79%, respectively. Bone union was achieved with a rate of 94% within 1 year after surgery, and nonunion (n = 1) and fracture (n = 2) were infrequently observed. Graft removal was performed in 7 cases, and the most common reason for the removal was infection (n = 5). The Musculoskeletal Tumor Society score was excellent in 23 cases of the available 29 cases. Frozen autograft reconstruction for AYAs showed excellent clinical outcomes, although the long-term follow-up is required. [ABSTRACT FROM AUTHOR]

Preservation of the sciatic nerve is difficult in cases of highly malignant soft tissue tumors closely surrounding the nerve. Herein, we present the first case of preservation of this nerve by combining an in-situ preparation technique (ISP; a technique enabling the preparation of neurovascular bundles without contamination by tumor cells) with intensive concurrent neoadjuvant chemo-radiotherapy with hyperthermia (RHC; radio-hyperthermo-chemotherapy). A 62-year-old man presented with a soft tissue mass in the right thigh and was diagnosed with undifferentiated pleomorphic sarcoma. The tumor arose in the multi-compartment areas of the posterior thigh muscles and was closely intertwined with the sciatic nerve. As preoperative therapy, RHC was performed for surgical down-staging and the tumor partially responded. Afterwards, wide resection of the tumor with preservation of the sciatic nerve using ISP was performed. Following the surgery, there has not been recurrence in the affected site and the functional outcomes of the lower extremity achieved 80% in the Musculoskeletal Tumor Society score. The patient is still alive with disease five years postoperatively. This is the first case in which ISP and RHC procedures were combined for the preservation of the neurovascular structure. Further study is needed for the validation of the feasibility of this method. [ABSTRACT FROM AUTHOR]

Background: A histological diagnosis obtained from an intraoperative frozen section (FS) during biopsy confirms the adequacy of tumor tissue in the specimen. However, some cases show a discrepancy among the intraoperative FS diagnosis, permanent section (PS) diagnosis of the biopsy specimen, and the final diagnosis of the excised tumor specimen. In this study, we retrospectively investigated the diagnostic accuracy of the FS and PS for different types of bone tumors. Methods: This study included 377 patients with 411 bone tumors who underwent tumor excision after an open biopsy with intraoperative FS diagnosis. FS, PS, and final diagnoses of the patients were classified into benign tumors/tumor-like lesions, intermediate malignancies, and malignant tumors. To assess diagnostic accuracy, the histological grades in FS and PS diagnoses were compared with those in the final diagnoses. Results: The overall diagnostic accuracies of FS and PS were 93% and 97%, respectively. The accuracy of FS and PS for histological grade was 84% and 93% for chondrogenic tumors, 90% and 96% for osteogenic tumors, 97% and 98% for osteoclastic giant cell-rich tumors, 100% and 100% for tumors of undefined neoplastic nature, and 95% and 99% for other bone tumors, respectively. Conclusion: These data suggest that surgical planning based on PS diagnosis is recommended for chondrogenic and osteogenic tumors. [ABSTRACT FROM AUTHOR]

With the aim of strengthening the scientific evidence of immune-cell therapy for cancer and further examining its safety, in October 2015, our hospital jointly established the Cancer Immune-Cell Therapy Evaluation Group (CITEG) with 39 medical facilities nationwide. Medical information, such as patients' background characteristics, clinical efficacy and therapeutic cell types obtained from each facility, has been accumulated, analyzed and evaluated by CITEG. In this prospective study, we analyzed the adverse events associated with immune-cell therapy until the end of September 2022, and we presented our interim safety evaluation. A total of 3839 patients with malignant tumor were treated with immune-cell therapy, with a median age of 64 years (range, 13–97 years) and a male-to-female ratio of 1:1.08 (1846:1993). Most patients' performance status was 0 or 1 (86.8%) at the first visit, and 3234 cases (84.2%) were advanced or recurrent cases, which accounted for the majority. The total number of administrations reported in CITEG was 31890, of which 960 (3.0%) showed adverse events. The numbers of adverse events caused by treatment were 363 (1.8%) of 19661 administrations of αβT cell therapy, 9 of 845 administrations of γδT-cell therapy (1.1%) and 10 of 626 administrations of natural killer cell therapy (1.6%). The number of adverse events caused by dendritic cell (DC) vaccine therapy was 578 of 10748 administrations (5.4%), which was significantly larger than those for other treatments. Multivariate analysis revealed that αβT cell therapy had a significantly greater risk of adverse events at performance status 1 or higher, and patients younger than 64 years, women or adjuvant immune-cell therapy had a greater risk of adverse events in DC vaccine therapy. Injection-site reactions were the most frequently reported adverse events, with 449 events, the majority of which were associated with DC vaccine therapy. Among all other adverse events, fever (228 events), fatigue (141 events) and itching (131 events) were frequently reported. In contrast, three patients had adverse events (fever, abdominal pain and interstitial pneumonia) that required hospitalization, although they were weakly related to this therapy; rather, it was considered to be the effect of treatment for the primary disease. Immune-cell therapy for cancer was considered to be a safe treatment without serious adverse events. [ABSTRACT FROM AUTHOR]

Background: Low-grade myofibroblastic sarcoma (LGMS) is described as a distinct atypical myofibroblastic tumor often with fibromatosis-like features and predilection for the head and neck, especially the oral cavity and larynx. LGMS arising in the levator scapulae muscle is extremely rare.Case Presentation: A 69-year-old woman was admitted to our hospital because she noticed a hard mass in her left neck six months prior. Magnetic resonance images (MRI) showed a soft tissue tumor of the left levator scapulae muscle. A core needle biopsy showed cellular fascicles or a storiform growth pattern of spindle-shaped tumor cells with minimally atypia. Immunohistochemistry revealed focally positive for α-smooth muscle actin (α-SMA), negative for S-100, and a low-grade spindle cell sarcoma was suspected. Following a biopsy, the tumor was resected with a wide surgical margin. Immunohistochemical staining was a positive for vimentin and α-SMA and negative for desmin, CD34, nuclear β-catenin, and h-caldesmon. LGMS diagnosis was determined based on the histopathological findings. The patient was alive with no evidence of disease eight years after the surgery.Conclusions: To the best of our knowledge, this is the first case report of LGMS arising in the levator scapulae muscle. In addition to the case report, 48 reports with 103 LGMS cases are reviewed and discussed. In previous reports of LGMS, there were 43 females and 60 males, with a mean age of 43.0 years (range, 2-75). There were 13 (12.6%) patients aged < 18 years, 67 (65.1%) patients aged 18 to 59 years, and 23 (22.3%) patients aged ≥60 years. The average tumor size was 4.4 cm (range: 0.4-22.0). The commonest sites of LGMS was the tongue. Tumor growth patterns were evaluated in 52 cases, and 44 cases (84.6%) showed infiltrative growth patterns. Local recurrence was 26.7%, and distant metastasis was 4.4%. Because of the locally aggressive feature, it is important to diagnose LGMS with biopsy and to excise the tumor with an adequately wide margin. [ABSTRACT FROM AUTHOR]

Background: For excised tumor specimens, histological grades can differ between the biopsy diagnosis and the final diagnosis. Methods: We retrospectively investigated the diagnostic accuracies of histological grades for frozen-section and permanent-section diagnoses from patients with soft-tissue tumors. Frozen-section, permanent-section, and final diagnoses were classified as benign tumors/tumor-like lesions, intermediate malignancies, or malignant tumors. Diagnostic accuracies of the histological grades from the frozen and permanent sections were evaluated by comparing the final diagnoses for the resected specimens. Results: The diagnostic accuracies of the histological grades for the frozen- and permanent-section diagnoses were 95% (387/408 lesions) and 97% (395/408 lesions), respectively. Among the tumor types, the diagnostic accuracies of the histological grades for the frozen-section and permanent-section diagnoses were 84% and 87% for adipocytic tumors, 87% and 91% for fibroblastic/myofibroblastic tumors, 99% and 100% for nerve-sheath tumors, 98% and 98% for fibrohistiocytic tumors, 90% and 98% for tumors of uncertain differentiation, 100% and 100% for vascular tumors, and 97% and 98% for other tumors, respectively. Conclusions: Histological grades from frozen-section diagnoses yielded low diagnostic accuracies in adipocytic and fibroblastic/myofibroblastic tumors. Treatment should be planned based on permanent-section diagnosis and radiological findings for these tumors. [ABSTRACT FROM AUTHOR]

Background: Subcutaneous adipose tissue represents an abundant source of multipotent adult stem cells named as Adipose-derived stem cells (ADSCs). With a cell sheet approach, ADSCs survive longer, and can be delivered in large quantities. We investigated whether intra-articular ADSC sheets attenuated osteoarthritis (OA) progression in a rabbit anterior cruciate ligament transection (ACLT) model.Methods: Fabricating medium containing ascorbate-2-phosphate was used to enhance collagen protein secretion by the ADSCs to make ADSC sheets. At 4 weeks after ACLT, autologous ADSC sheets were injected intra-articularly into the right knee (ADSC sheets group), and autologous cell death sheets treated by liquid nitrogen were injected into the left knee (control group). Subsequent injections were administered once weekly. Femoral condyles were compared macroscopically and histologically.Results: Macroscopically, OA progression was significantly milder in the ADSC sheets than in the control groups. Histologically, control knees showed obvious erosions in the medial and lateral condyles, while cartilage was retained predominantly in the ADSC sheets group. Immunohistochemically, MMP-1, MMP-13, ADAMTS-4 were less expressive in the ADSC sheets than in the control groups.Conclusions: Periodic ADSC sheets injections inhibited articular cartilage degeneration without inducing any adverse effects. A large quantity of autologous ADSCs delivered by cell sheets homed to the synovium and protected chondrocytes. [ABSTRACT FROM AUTHOR]

Extraskeletal osteosarcoma is a rare soft tissue sarcoma and typically appears as a solid mass with variable mineralization. A few cases of extraskeletal osteosarcoma have shown extensive hemorrhagic changes or bleeding due to its high-grade malignancy; however, to the best of our knowledge, no previous reports have described the pathological characteristics of tumors with non-hemorrhagic cystic change. The present report discusses three cases involving cystic lesions with a solid area at the periphery that arose in soft tissues. The large cystic spaces contained only yellowish-brown fluid and little or no blood, with no clear pathological necrotic tissue. The solid component comprised a focal area of osteoid production by highly anaplastic sarcomatous cells. All of the cases showed high-grade malignancy histologically, and the average maximum diameter was approximately 175 mm. The tumors were located at the adductor muscles in two cases and at the intermuscular region of the hamstring muscles in one case. All of the patients consulted a doctor after more than half a year had passed since the recognition of swelling or a mass on their affected extremities. Surgical treatment was performed for all patients. One patient had lymph node metastasis, and another had lymphoedema after surgery, but no histological invasion to the lymphatic ducts was observed in the excised specimen. Degenerative changes in the fluid content over a long time-course as a result of tumor bleeding or necrosis, rather than lymphorrhea by lymphatic channel invasion of the tumor, might have contributed to the formation of the cystic lesion. Only 1 patient who underwent chemotherapy remained clinically disease-free over 10 years after surgery. Chemotherapy regimens for osteosarcoma rather than those for soft tissue sarcoma are mostly effective for extraskeletal osteosarcoma, so the diagnosis by a biopsy is essential. It is important to consider extraskeletal osteosarcoma in the differential diagnosis of soft tissue tumor with cystic form and calcification and a long clinical course before consulting a doctor. [ABSTRACT FROM AUTHOR]

Background: Difficult resection of tumors from regions with complex local anatomy, such as the pelvis and sacrum, is likely to result in inadequate surgical margins (intralesional or marginal); this is because three-dimensional osteotomy is difficult particularly around the acetabulum. Additionally, removal of the joint makes reconstruction very difficult; thus, retention of good function also becomes difficult. In musculoskeletal oncology, computer navigation systems are still not widely used to prevent tumor-positive margins. We performed wide excision with guidance from a computer navigation system and reconstruction using frozen bone autografts for malignant pelvic bone tumors in two patients, and we obtained excellent functional and oncological outcomes. Here we present these patients and discuss our approach.Case Presentation: Case 1: A 12-year-old girl presented with Ewing sarcoma of the left pelvis (PI-II). We performed wide excision assisted by a computer navigation system with the osteotomy of the load surface of acetabulum and reconstruction using a frozen bone autograft. At the final follow-up, she showed excellent function and was alive without the disease. Moreover, she did not have osteoarthritis of the left hip joint. Case 2: A 71-year-old woman presented with dedifferentiated chondrosarcoma of the right pelvis (PII-III). We performed wide excision assisted by a computer navigation system with osteotomy avoiding load surface of the acetabulum and reconstruction using a frozen bone autograft; there was no tumor at the load surface. At the final follow-up, she showed good function, was alive without the disease, and did not have osteoarthritis of the left hip joint.Conclusions: Wide excision assisted by a computer navigation system and reconstruction using a frozen bone autograft are very useful for the management/treatment of extremely difficult cases such as malignant pelvic bone tumors, particularly those including the acetabulum. [ABSTRACT FROM AUTHOR]

Presents a letter to the editor, on causes of acute hepatic failure.

Backgrounds: Immune checkpoint inhibitors (ICIs) can significantly prolong the survival of patients with advanced non‐small‐cell lung cancer (NSCLC); however, few studies on the therapeutic effects of ICIs on bone metastases were performed. Methods: This retrospective study aimed to investigate the therapeutic effects of ICIs and determine predictors of favorable ICI response and prognosis in 55 advanced NSCLC patients with bone metastases who initiated ICI treatment between 2016 and 2019, with a mean follow‐up period of 23.2 months. Patients were classified into responders (complete or partial response) and non‐responders (stable or progressive disease) according to the MD Anderson Cancer Center (MDA) criteria, and the predictors of therapeutic response were identified using multivariate logistic regression analysis. Furthermore, overall survival from the time of ICI administration to the final follow‐up or death was evaluated, and prognostic predictors were identified using Cox proportional hazards regression analysis. Results: ICI response rate was 30.9% (complete in three cases, partial in 14). Median survival time was 9.3 months, with 1‐year and 2‐year survival rates of 40.6% and 19.3%, respectively. Responders survived significantly longer than non‐responders (p = 0.03). Based on the receiver operating characteristic curve, the predictive cutoff value of the pretreatment neutrophil‐to‐lymphocyte ratio (NLR) was 2.1. Multivariate analysis identified female sex (p = 0.03), use of ICIs as first‐line therapy (p < 0.01), and NLR <2.1 (p = 0.03) as significant predictors of therapeutic response, whereas concomitant use of a bone‐modifying agent (p < 0.01), Katagiri score ≤6 points (p < 0.01), and NLR <2.1 (p = 0.02) were identified as significant predictors of good prognosis. Conclusions: This study identified some novel predictors for favorable therapeutic response and prognosis in advanced NSCLC patients with bone metastases undergoing ICI treatment. Pretreatment NLR less than 2.1 can be considered the most important predictor. [ABSTRACT FROM AUTHOR]

Background: A sclerosing epithelioid fibrosarcoma (SEF) is an uncommon tumor of the deep soft tissue. An SEF has been described as a low-grade tumor with high local recurrence and metastatic rates. Generally, in bone and soft tissue tumors, a resection of the biopsy route is recommended; however, there is limited evidence with respect to the dissemination of the tumor tissue during a needle biopsy. Case presentation: A mass in the right pelvic cavity, with no symptoms, was observed in a 45-year-old woman during a gynecological examination. Computed tomography (CT) revealed a multilocular mass with calcification in the pelvic cavity. The magnetic resonance imaging (MRI) showed an iso-signal intensity on T1 weighted images and hypo- and iso-signal intensity on T2 weighted images. The CT-guided core needle biopsy was performed using a dorsal approach, and the biopsy diagnosis was a low-grade spindle cell tumor. The tumor was excised using an anterior approach. The tumor tissue comprised spindle cells and epithelioid cells with irregular nuclei, and the immunohistological analysis was positive for vimentin and epithelial membrane antigen, which was consistent with a diagnosis of sclerosing epithelioid fibrosarcoma. Five years after the surgery, the MRI showed a tumor recurrence in the subcutaneous tissue of the right buttock, which was consistent with the needle biopsy tract. The patient underwent a tumor excision, and the resected tumor was similar to the primary tumor. Conclusions: The recurrent tumor was excised with a surgical margin, and the tumor specimen had the histological features of a sclerosing epithelioid fibrosarcoma. It was difficult to investigate the association of the core needle biopsy with the tumor recurrence because the approach of the biopsy tract is usually same as that used in a tumor excision. However, the present case indicated the tumor may recur in the biopsy tract of a soft tissue sarcoma. Surgeons should be aware of the possibility of disseminating tumor tissues in a needle biopsy. [ABSTRACT FROM AUTHOR]

Calcium phosphate cement (CPC) is often used to repair bone defects that occur after bone tumor and fracture treatment. To address bone defect cases with a high infection risk, developing CPCs with a longlasting wide-spectrum antibacterial effect is critical. Povidone-iodine has a wide antibacterial spectrum. Though there have been some reports of CPC containing antibiotics, no report of CPC with iodine has been described. In this study, the antibacterial effect and biological reaction of CPC impregnated with iodine was investigated. Iodine release from CPC and bone cement with various iodine contents (2.5, 5, and 20%) was evaluated, and 5 %-iodine CPC retained more iodine than the other CPCs after one week. Antibacterial activity against Staphylococcus aureus and Escherichia coli was also investigated, showing that 5 %-iodine had an antibacterial effect for up to eight weeks. Cytocompatibility was assessed, and 5 %-iodine CPC showed the same amount of fibroblast colony formation as control samples. CPCs with varying iodine contents (0, 5, and 20%) were then inserted into lateral femora of Japanese white rabbits for histological analysis. Osteoconductivity was evaluated using scanning electron microscopy, and hematoxylin-eosin staining. Consecutive bone formation was observed around all CPCs at eight weeks. These results indicate that CPC impregnated with iodine exhibits antimicrobial activity and cytocompatibility, and therefore, it may be effective for bone defect cases with high infection risk. Graphical Abstract [ABSTRACT FROM AUTHOR]

Periprosthetic joint infection (PJI) is characterized by biofilm infection, which is difficult to alleviate while preserving implant integrity. Furthermore, long-term antibiotic therapy may increase the prevalence of drug-resistant bacterial strains, necessitating a non-antibacterial approach. Adipose-derived stem cells (ADSCs) exert antibacterial effects; however, their efficacy in PJI remains unclear. This study investigates the efficacy of combined intravenous ADSCs and antibiotic therapy in comparison to antibiotic monotherapy in a methicillin-sensitive Staphylococcus aureus (MSSA)-infected PJI rat model. The rats were randomly assigned and equally divided into 3 groups: no-treatment group, antibiotic group, ADSCs with antibiotic group. The ADSCs with antibiotic group exhibited the fastest recovery from weight loss, with lower bacterial counts (p = 0.013 vs. no-treatment group; p = 0.024 vs. antibiotic group) and less bone density loss around the implants (p = 0.015 vs. no-treatment group; p = 0.025 vs. antibiotic group). The modified Rissing score was used to evaluate localized infection on postoperative day 14 and was the lowest in the ADSCs with antibiotic group; however, no significant difference was observed between the antibiotic group and ADSCs with antibiotic group (p < 0.001 vs. no-treatment group; p = 0.359 vs. antibiotic group). Histological analysis revealed a clear, thin, and continuous bony envelope, a homogeneous bone marrow, and a defined, normal interface in the ADSCs with antibiotic group. Moreover, the expression of cathelicidin expression was significantly higher (p = 0.002 vs. no-treatment group; p = 0.049 vs. antibiotic group), whereas that of tumor necrosis factor (TNF)-α and interleukin(IL)-6 was lower in the ADSCs with antibiotic group than in the no-treatment group (TNF-α, p = 0.010 vs. no-treatment group; IL-6, p = 0.010 vs. no-treatment group). Thus, the combined intravenous ADSCs and antibiotic therapy induced a stronger antibacterial effect than antibiotic monotherapy in a MSSA-infected PJI rat model. This strong antibacterial effect may be related to the increased cathelicidin expression and decreased inflammatory cytokine expression at the site of infection. [ABSTRACT FROM AUTHOR]

Purpose: In 1999, we developed a technique using frozen autografts-tumour-containing bone treated with liquid nitrogen-for the reconstruction of malignant bone tumours. The purpose of this study was to evaluate the functional and oncological outcomes of frozen autografts for intercalary reconstruction of malignant bones and soft tissue tumours.Methods: This retrospective study was designed to assess 34 patients of mean age 35 (range, 6-79) years. The mean follow-up period was 62 (24-214) months. The median length of the frozen autografts was 138.4 ± 60.39 (50-290) mm.Results: Postsurgically, 20 patients remained disease-free, seven patients survived with no evidence of disease, five patients were alive with disease, and two patients died of disease. The five- and ten-year survival rates of the frozen autografts were 91.2% and the mean International Society of Limb Salvage score was 90%. Complete bony union was achieved in 97% of the patients. There were five cases of nonunion, six cases of fracture, two cases of deep infection and four cases of local recurrence.Conclusion: Utilizing intercalary frozen autografts for patients with a nonosteolytic primary or secondary bone tumour without involvement of the subchondral bone is a good alternative treatment, because it is a straightforward biological technique and can provide excellent limb function. [ABSTRACT FROM AUTHOR]

Background: The p53 protein in mesenchymal stem cells (MSCs) regulates differentiation to osteogenic or adipogenic lineage. Because p53 function is depressed in most malignancies, if MSCs in malignancy also have p53 hypofunction, differentiation therapy to osteogenic or adipogenic lineage may be an effective treatment. We therefore wished to begin to explore this idea by evaluating atypical lipomatous tumor/well-differentiated liposarcoma (ALT/WDL) cells, because murine double minute 2 (MDM2) gene amplification, which leads to p53 hypofunction, is found in almost all ALT/WDLs.Questions/purposes: We compared osteogenic and adipogenic differentiation potency between MSCs isolated and cultured from normal adipose tissues and ALT/WDLs from the same patients.Methods: During tumor resections in six patients with ALT/WDL, we analyzed 3 mL of tumor, and for comparison, we harvested a similar amount of normal-appearing subcutaneous adipose tissue from an area remote from the tumor for comparison. Adipogenic differentiation potency was quantitatively assessed using spectrometry after oil red O staining. Osteogenic differentiation potency was semiquantitatively assessed by measuring a specific colored area after alkaline phosphatase (ALP) and alizarin red S staining. ALP is related to preosseous cellular metabolism, and alizarin red is related to calcium deposits in cell culture. There were three observers for each assessment, and each assessment (including induced-differentiation and histologic analysis) was performed in duplicate. We then analyzed the mechanism of the difference of osteogenic differentiation potency using the MDM2-specific inhibitor Nutlin-3 at various concentrations.Results: In terms of adipogenic differentiation potency, contrary to our expectations, more fatty acid droplets were observed in MSCs derived from normal fat than in MSCs derived from ALT/WDL, although we found no significant difference between MSCs derived from ALT/WDL and MSCs derived from normal fat; the mean differentiation potency values (normal adipose tissue versus ALT/WDL) (± SD) were 0.34 (SD, ± 0.13; 95% CI, 0.24-0.44) versus 0.25 (SD, ± 0.10; 95% CI, 0.18-0.33; p = 0.22). By contrast, we found greater osteogenic differentiation potency in MSCs derived from ALT/WDL than in MSCs derived from normal fat. The mean differentiation potency values (normal adipose tissue versus ALT/WDL) (±SD) based on ALP staining was 1.0 versus 17 (SD, ± 36; 95% CI, -2.8 to 38; p = 0.04). However, we found no differences based on alizarin red S staining; mean differentiation potency value (normal adipose tissue versus ALT/WDL) (± SD) was 1.0 versus 4.2 (SD, ± 4.8; 95% CI, 1.3-7.2; p = 0.58). The gap of osteogenic differentiation potency between MSCs from normal adipose tissue and ALT/WDL was decreased as MDM2-inhibitor Nutlin-3 concentration increased.Conclusions: MSCs derived from ALT/WDL had higher osteogenic differentiation potency based on ALP staining, which disappeared as Nutlin-3 concentration increased, suggesting that could be caused by amplified MDM2 in ALT/WDL. Future laboratory studies might mechanistically confirm the gene and protein expression, and based on the mechanism of the gap of differentiation potency, if p53 contrast between MSCs in tumor and normal tissue could be stimulated, less-toxic and more-effective differentiation therapy to MSCs in malignancies might be developed. [ABSTRACT FROM AUTHOR]

Background: The linea aspera is the rough, longitudinal crest on the posterior surface of the femoral shaft. Most orthopedic surgeons depend on the linea aspera as an intraoperative landmark identifying the true posterior aspect of the femur. We investigated the position of the linea aspera to verify whether the surgeon can rely on this accepted belief.Material and Method: One hundred and thirty-three femora from 73 patients were evaluated. Four CT cuts were done of the mid femur, and we measured the angle of rotation of the linea aspera at each cut.Results: The linea aspera was externally rotated in most femora evaluated; average angles of rotation were 15.4°, 14°, 11.7°, and 11.5° at 10, 15, 20, and 25 cm from the intercondylar line, respectively. The angle of rotation of the linea aspera was positively correlated with femoral neck anteversion angle and negatively with age.Conclusion: The linea aspera is exactly posterior in a minority of individuals, while it is externally rotated to varying degrees in the majority of individuals. The degree of rotation was positively correlated with femoral neck anteversion angle, and negatively with age. To avoid implant malrotation, accurate estimation of the rotation angle should be determined preoperatively.Level Of Evidence: Level IV. [ABSTRACT FROM AUTHOR]

Sarcoma is a rare cancer, and little is known about the etiology, lifestyle epidemiology, and actual circumstances of treatment in hospitals in Japan. Understanding these issues is essential for the effective prevention and treatment of sarcoma. We therefore investigated the incidence of a personal and family cancer history in a total of 1320 sarcoma patients at the National Cancer Center Hospital. In addition, obesity, hypertension, dyslipidemia, diabetes mellitus, drinking, smoking, age and sex were compared in a descriptive study of 1159 of these sarcoma patients who were ≥ 20 years of age, and 7738 controls derived from the National Health and Nutrition Examination Survey in Japan. A total of 8% of sarcoma patients had a personal history of another cancer, and 30% of soft tissue sarcoma patients had a family cancer history in a first-degree relative (malignant peripheral nerve sheath tumor, 52%; leiomyosarcoma, 46%). A smoking habit was associated with the development of sarcoma (odds ratio [OR], 2.05; 95% confidence interval, 1.78–2.37; p < 0.01). According to the histology, the ORs for undifferentiated pleomorphic sarcoma (UPS) of bone, UPS of soft tissue, and liposarcoma were 5.71, 3.04, and 2.92, respectively. A family cancer history may be associated with certain soft tissue sarcomas, and a smoking habit was significantly associated with the development of sarcomas; however, further studies are necessary. [ABSTRACT FROM AUTHOR]

Background: A tenosynovial giant cell tumor (T-GCT) is a benign synovial tumor arising from the synovium, bursae, or tendon sheath. It can be intra- or extra-articular and localized or diffuse. Diffuse T-GCT is considered as a locally aggressive. Positron emission tomography (PET) with fluorine-18 fluorodeoxyglucose with computed tomography (FDG PET/CT) is widely used to differentiate malignant from benign tumors and to detect distant metastasis. However, FDG PET/CT is limited by false-positive findings. In this study, we present two cases of T-GCT that developed in unusual locations and were confused with malignant tumors. The final diagnoses were histologically confirmed as T-GCTs.Case Presentation: Case 1. A 45-year-old Japanese female presented with a left choroidal melanoma and an abnormal lesion adjacent to the first cervical (C1) lamina confirmed by a PET scan (maximum standardized uptake value [SUVmax] =9.9 g/ml). MRI of the neck also detected a soft tissue mass (14.6 × 7.7 × 7 mm) adjacent to the C1 lamina. The choroidal melanoma was treated by heavy carbon ion radiotherapy. Although the size of the C1 soft tissue tumor remained unchanged, a CT-guided biopsy confirmed the diagnosis of the neck mass as a T-GCT. Case 2. A 15-year-old Japanese male with multiple type 1 neurofibromatosis presented with a soft tissue mass (26.1 × 24.7 × 11.5 mm) of the extra-articular hip joint that was coincidentally detected by FDG PET/CT during examination of a mediastinal soft tissue mass. SUVmax of the mediastinal lesion was 2.6 g/ml and of the hip lesion was 12.8 g/ml. Thus, differentiation from a malignant tumor, such as a malignant peripheral nerve sheath tumor, was necessary. An open biopsy was performed, and the frozen section was diagnosed as T-GCT. The tumor was excised, and the final histological diagnosis confirmed T-GCT.Conclusion: T-GCT can show high FDG uptake, which might be confused with malignancy. Although MRI findings and location might help in the diagnosis of a T-GCT, careful assessment is mandatory, especially in unusual locations. [ABSTRACT FROM AUTHOR]

Limb salvage surgery has become the standard treatment for malignant primary bone tumors in the extremities. Limb salvage represents a challenge in skeletally immature patients. Several treatment options are available for limb reconstruction after tumor resection in children. We report our results using the technique of epiphyseal sparing and reconstruction with frozen autograft bone in 18 children. The mean follow-up period for the all patients included in this study is 72 ± 26 m. Eight patients remained disease-free, seven patients lived with no evidence of disease, two were alive but with disease, and one patient died of the disease. Five- and ten-year rates of survival were 94.4%. Graft survival at 5 and 10 years was 94.4%. Functional outcome using the Enneking scale was excellent in 17 patients (94.4%) and poor in one patient (5.5%). Complications include 2 nonunions, 2 fractures, 2 deep infections, 1 soft tissue recurrence, and leg length discrepancy in 7 cases. This technique is a good reconstructive choice in a child with a nonosteolytic primary or secondary bone tumor, responsive to chemotherapy, without involvement of the articular cartilage. It is a straight forward, effective, and biological technique, which affords immediate mobilization of joints and possible cryoimmune effects, with excellent long term functional outcome and less complication. [ABSTRACT FROM AUTHOR]

Introduction. The main indication for knee arthrodesis in tumor surgery is a tumor that requires an extensive resection in which the joint surface cannot be preserved. We report a patient that had knee desarthrodesis 41 years after giant cell tumor resection followed by a knee arthrodesis. This is the longest reported follow-up after desarthrodesis and conversion to total knee arthroplasty (TKA), almost ten years. Case Report. A 71-year-old man with a distal femoral giant cell tumor had undergone a resection of the distal femur and knee arthrodesis using Kuntscher nail in 1962. In July 2003 he experienced gradually increasing pain of his left knee. We performed a desarthrodesis and conversion to TKA in 2005. The postoperative period passed uneventfully as his pain and gait improved, with gradually increasing range of motion (ROM) and no infection. He now walks independently, with no brace or contractures. Conclusion. Desarthrodesis of the knee joint and conversion to TKA are a difficult surgical choice with a high complication risk. However, our patient’s life style has improved, he has no pain, and he can ascend and descend stairs more easily. The surgeon has to be very meticulous in selecting a patient for knee arthrodesis and counseling them to realize that their expectations may not be achievable. [ABSTRACT FROM AUTHOR]