Fluorescence-guided assessment of bone and soft-tissue sarcomas for predicting the efficacy of telomerase-specific oncolytic adenovirus.

Bone and soft-tissue sarcomas are rare malignancies with histological diversity and tumor heterogeneity, leading to the lack of a common molecular target. Telomerase is a key enzyme for keeping the telomere length and human telomerase reverse transcriptase (hTERT) expression is often activated in most human cancers, including bone and soft-tissue sarcomas. For targeting of telomerase-positive tumor cells, we developed OBP-301, a telomerase-specific replication-competent oncolytic adenovirus, in which the hTERT promoter regulates adenoviral E1 gene for tumor-specific viral replication. In this study, we present the diagnostic potential of green fluorescent protein (GFP)-expressing oncolytic adenovirus OBP-401 for assessing virotherapy sensitivity using bone and soft-tissue sarcomas. OBP-401-mediated GFP expression was significantly associated with the therapeutic efficacy of OBP-401 in human bone and soft-tissue sarcomas. In the tumor specimens from 68 patients, malignant and intermediate tumors demonstrated significantly higher expression levels of coxsackie and adenovirus receptor (CAR) and hTERT than benign tumors. OBP-401-mediated GFP expression was significantly increased in malignant and intermediate tumors with high expression levels of CAR and hTERT between 24 and 48 h after infection. Our results suggest that the OBP-401-based GFP expression system is a useful tool for predicting the therapeutic efficacy of oncolytic virotherapy on bone and soft-tissue sarcomas.

Conservative treatment of fragility fracture of the pelvis: A retrospective study.

BACKGROUND: Although an increasing number of studies have reported the usefulness of early minimally invasive surgery (MIS) or fragility fracture of the pelvis (FFP), MIS is difficult to perform in every hospital, partly because of equipment problems. Moreover, different opinions exist on FFP treatment methods and the indication for surgery is usually determined by the fracture type. Since our hospital follows a conservative approach as the basic treatment, this study examined the outcomes of such an FFP approach. HYPOTHESIS: FFP outcomes are influenced by the fracture type and walking ability before the injury. PATIENTS AND METHODS: We investigated the bone fusion rate, bone fusion duration, unloading duration, walking ability trends, and outcomes in 76 patients with FFP treated conservatively at our hospital. RESULTS: The union rate, mean period until union, and follow-up period were 93.4%, 3.3 months, and 14.3 months, respectively. Walking ability significantly decreased from 5.1 points before the injury to 4.4 points during the last follow-up (p<0.01). The average unloading period was 12.8 days, and FFPs showed a high bone fusion rate, even with conservative treatment. DISCUSSION: Most patients eventually returned to their pre-injury status despite slightly decreased walking ability. Given the invasive nature of surgery, the indications for surgery should be carefully assessed after considering the risk-benefit ratio. LEVEL OF EVIDENCE: III; retrospective study.

Application of a Navigated Drill for Cervical Pedicle Screw Insertion at C3-6.

Background Perforation of the cervical pedicle screw, especially lateral perforation, may lead to critical complications, such as vertebral artery injury. Sub-axial cervical spines (C3-6) are at risk of complications because these levels have limited area and angle. This study aimed to compare a navigated drill and a navigated probe for the insertion of cervical pedicle screws at C3-6. Methodology This retrospective study included 106 patients treated with cervical pedicle screws at C3-6. In total, 52 patients with 200 cervical pedicle screws using a navigated drill (group D) and 54 patients with 170 cervical pedicle screws using a navigated probe (group P) were compared. The perforation rate, anatomical medial angle of the pedicle, and actual angle of the screw were investigated using computed tomography. The planning error was defined as when the pedicle screw was applied for a small pedicle width of <3.5 mm. All perforations except for planning errors were defined as technical perforations. Results Grade 1 screw perforations were identified in 16 and 17 screws in groups D and P, respectively. Overall, 88% of the perforations were medial in group D, and 82% of perforations were lateral in group P. Technical perforations were found in 7/191 (3.7%, group D) and 15/168 (8.9%, group P) screws. There were no significant differences in the anatomical angle of the pedicle between the groups. The mean medial angle of the pedicle screws was 24.7° (group D) and 30.9° (group P) (p < 0.05). Conclusions The perforation rate of group D was less than half of that of group P. This was because a navigated drill was able to create a bony pilot hole at the hard medial cortical wall of the pedicle with a small medial angle, which was difficult to do with a navigated probe. A navigated drill can be useful for cervical pedicle screw insertion at C3-6 because of its easiness and safety.

Pneumocephalus After Anterior Lumbar Spinal Surgery Due to Trauma: A Case Report.

Pneumocephalus as a complication of anterior lumbar spinal surgery is extremely rare. A 53-year-old male patient presented with L4 fracture. Posterior fixation from L3 to L5 was conducted one day after the trauma. As the patient's neurological deficit persisted, additional anterior surgery by L4 vertebral body replacement was performed on the 19th day. Both surgeries were completed without obvious intraoperative complications. Two weeks after the anterior lumbar surgery, the patient complained of severe headaches, and computed tomography scan revealed pneumocephalus and massive fluid retention in the abdomen. The symptoms improved with conservative treatment, including bed rest, spinal drainage, intravenous drip infusion, and prophylactic administration of antibiotics. Due to the lack of tamponade effect in the soft tissues, a large amount of cerebrospinal fluid leakage may induce and cause progression of pneumocephalus in anterior dural injury.

Minimally invasive surgery technique for unstable pelvic ring fractures with severe vertical shear displacement: A retrospective study.

BACKGROUND: Unstable pelvic fractures, especially vertical shear fractures, require surgery for correct reduction, rigid fixation, and improved postoperative outcomes. Herein, we assess the effectiveness of our minimally invasive procedure for the management of unstable pelvic fractures. HYPOTHESIS: We hypothesized that this procedure would be useful for the management of unstable pelvic fractures. PATIENTS AND METHODS: This study included 28 patients with unstable pelvic fractures (vertical shear injuries; AO types C1-3) treated using minimally invasive surgery for spinopelvic fixation (MIS-SP) between 2014 and 2020 (mean follow-up time, 15 months). The MIS-SP requires four percutaneous pedicle screws and four iliac screw insertions. Subsequently, reduction and fixation are performed. RESULTS: The mean preoperative displacement of the posterior pelvic elements in craniocaudal correction was 17.6 (range, 9.0-32.2) mm. The mean length of the craniocaudal reduction was 16.5 (8.1-30.1) mm, with a mean reduction rate of 93.5% (78%-100%). The mean length of the mediolateral reduction was 11.3 (3.9-19.6) mm, with a mean reduction rate of 87.3% (76%-100%). DISCUSSION: Our novel reduction and fixation procedure is a powerful, minimally invasive option for the treatment of unstable pelvic ring fractures. LEVEL OF EVIDENCE: III.

NanoSIMS Analysis of Rare Earth Elements in Silicate Glass and Zircon: Implications for Partition Coefficients.

We have developed a method to analyze all rare earth elements in silicate glasses and zircon minerals using a high lateral resolution secondary ion mass spectrometer (NanoSIMS). A 2nA O- primary beam was used to sputter a 7-8-µm diameter crater on the sample surface, and secondary positive ions were extracted for mass analysis using an accelerating voltage of 8 kV. A high mass resolving power of 9,400 at 10% peak height was attained to separate heavy REE from oxide of light REE. A multi-collector system combined with peak-jumping by magnetic field was adjusted to detect REEs and silicon-30 for calibration. Based on results of NIST SRM610 glass, sensitivities of REEs vary from 3 cps/ppm/nA of Lu to 13 cps/ppm/nA of Eu. Reproducibility of REE/Si ratios is better than 18% at 2σ. Secondary ion yields of REEs show positive relationships with their ionization potential of second valence. REEs of AS3, QGNG, and Torihama zircons were measured and calibrated against those of 91500 standard zircon. SIYs of REEs of zircon are identical to those of the glass standard. AS3 and QGNG data are generally consistent with those of previous work. Torihama REE data combined with the whole rock data provide partition coefficients of REEs between silicate melt and zircon. The relationship between these coefficients and ionic radius is explained by an elastic moduli model.

Liquid Biopsy Targeting Monocarboxylate Transporter 1 on the Surface Membrane of Tumor-Derived Extracellular Vesicles from Synovial Sarcoma.

The lack of noninvasive biomarkers that can be used for tumor monitoring is a major problem for soft-tissue sarcomas. Here we describe a sensitive analytical technique for tumor monitoring by detecting circulating extracellular vesicles (EVs) of patients with synovial sarcoma (SS). The proteomic analysis of purified EVs from SYO-1, HS-SY-II, and YaFuSS identified 199 common proteins. DAVID GO analysis identified monocarboxylate transporter 1 (MCT1) as a surface marker of SS-derived EVs, which was also highly expressed in SS patient-derived EVs compared with healthy individuals. MCT1+CD9+ EVs were also detected from SS-bearing mice and their expression levels were significantly correlated with tumor volume (p = 0.003). Furthermore, serum levels of MCT1+CD9+ EVs reflected tumor burden in SS patients. Immunohistochemistry revealed that MCT1 was positive in 96.7% of SS specimens and its expression on the cytoplasm/plasma membrane was significantly associated with worse overall survival (p = 0.002). Silencing of MCT1 reduced the cellular viability, and migration and invasion capability of SS cells. This work describes a new liquid biopsy technique to sensitively monitor SS using circulating MCT1+CD9+ EVs and indicates the therapeutic potential of MCT1 in SS.

Clinical relevance and functional significance of cell-free microRNA-1260b expression profiles in infiltrative myxofibrosarcoma.

Infiltrative tumor growth into adjacent soft tissues is a major cause of the frequent recurrence and tumor-related death of myxofibrosarcoma (MFS), but no useful biomarkers reflecting tumor burden and infiltrative growth are available. While emerging evidence suggests a diagnostic and functional role of extracellular/circulating microRNA (miRNA) in various malignant diseases, their significance in MFS patients remains unknown. Global miRNA profiling identified four upregulated miRNAs in MFS patient sera and culture media of MFS cells. Among these, serum miR-1260b level was significantly upregulated in patient serum discriminating from healthy individuals and closely correlated with clinical status and tumor dynamics in MFS-bearing mice. In addition, high miR-1260b expression in serum was correlated with radiological tail-like patterns, characteristic of the infiltrative MFS. The extracellular miR-1260b was embedded in tumor-derived extracellular vesicles (EVs) and promoted cellular invasion of MFS through the downregulation of PCDH9 in the adjacent normal fibroblasts. Collectively, circulating miR-1260b expression may represent a novel diagnostic target for tumor monitoring of this highly aggressive sarcoma. Moreover, EV-miR-1260b could act as a transfer messenger to adjacent cells and mediate the infiltrative growth of MFS, providing new insights into the mechanism of infiltrative nature via crosstalk between tumor cells and their microenvironment.

Venous Thromboembolism in Patients with Acute Thoracolumbar Spinal Cord Injury.

Venous thromboembolism (VTE) is a major complication in patients with acute spinal cord injury. There are few reports of VTE with acute thoracolumbar spinal cord injury (TLSCI). We assessed the incidence of VTE with acute TLSCI using color Doppler ultrasonography. We retrospectively assessed 75 patients with acute TLSCI (T1 to L1). All patients were surgically treated. VTE of the lower extremity and pelvis was assessed using color Doppler ultrasound regardless of whether symptoms were present. This retrospective study included patients who were assessed between 6 and 10 days (mean 8.1 days) after injury. VTE was detected in 27 of the 75 patients (35.7%) with or without paralysis. Of the 13 patients who had complete motor paralysis, 8 (62%) had VTE; of the 31 patients with incomplete motor paralysis, 10 (32%) had VTE, and of the 31 patients without motor paralysis, 9 (29%) had VTE. Among the patients with TLSCI, those with VTE had a significantly higher mean age than those without. The incidence of VTE in TLSCI patients is not related to the severity of paralysis in a Japanese population. The incidence appears to be related primarily to age.

Clinical and Functional Significance of Intracellular and Extracellular microRNA-25-3p in Osteosarcoma.

Although there is considerable evidence indicating that the dysregulation of microRNAs (miRNAs) in malignant tumors plays a role in tumor development, the overall function of miRNAs and their clinicopathological significance are not well understood. In this retrospective analysis of 45 biopsy specimens from osteosarcoma (OS) patients, we investigated the functional and clinical significance of miR-25-3p in OS, which we previously identified as a highly expressed miRNA in OS patients' serum. We observed that miR-25-3p dysregulation in human OS tissues was negatively correlated with the clinical prognosis, whereas the expression level of its target gene, Dickkopf WNT Signaling Pathway Inhibitor 3 (DKK3), was positively correlated with the clinical prognosis. Endogenous miR-25-3p upregulation promoted tumor growth, invasion, and drug resistance, which was consistent with DKK3 silencing in OS cells. In addition, secretory miR-25-3p was embedded in tumor-derived exosomes, where it promoted capillary formation and the invasion of vascular endothelial cells. Overall, our results show that miR-25-3p has intracellular and extracellular oncogenic functions as well as clinicopathological relevance in OS, indicating its potential as a novel diagnostic and therapeutic tool for the clinical management of this disease.

Circulating MicroRNA-92b-3p as a Novel Biomarker for Monitoring of Synovial Sarcoma.

The lack of useful biomarkers is a crucial problem for patients with soft tissue sarcomas (STSs). Emerging evidence has suggested that circulating microRNAs (miRNAs) in body fluids have novel impact as biomarkers for patients with malignant diseases, but their significance in synovial sarcoma (SS) patients remains unknown. Initial global miRNA screening using SS patient serum and SS cell culture media identified a signature of four upregulated miRNAs. Among these candidates, miR-92b-3p secretion from SS cells was confirmed, which was embedded within tumour-derived exosomes rather than argonaute-2. Animal experiments revealed a close correlation between serum miR-92b-3p levels and tumour dynamics. Clinical relevance was validated in two independent clinical cohorts, and we subsequently identified that serum miR-92b-3p levels were significantly higher in SS patients in comparison to that in healthy individuals. Moreover, serum miR-92b-3p was robust in discriminating patients with SS from the other STS patients and reflected tumour burden in SS patients. Overall, liquid biopsy using serum miR-92b-3p expression levels may represent a novel approach for monitoring tumour dynamics of SS.

[Solitary Peripheral Pulmonary Squamous Cell Papilloma;Diagnostic Significance of 18F-fluorodeoxyglucose Positron Emission Tomography Findings].

The patient was a 79-year-old woman who had received enucleation of right pulmonary papilloma 7 years earlier. She experienced bloody sputum and was therefore referred to our hospital. Chest computed tomography revealed a mass shadow(21 mm) in the right upper lobe (S2). By bronchoscopy, there was no bulging lesion in the visible range. SCC and CEA increased to 6.4 ng/ml and 6.42 ng/ml, respectively. Whole-body 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) showed increased FDG uptake in the region of the right-lung mass shadow (maximum standardized uptake value 12.95). Since malignancy could not be ruled out, a wedge resection was performed. The post-operative histopathologic diagnosis was squamous cell papilloma. Our literature review showed 12 out of 14 cases with solitary papilloma of the peripheral lung to have increased FDG uptake. Ki-67 positive cells were confirmed in the basal layers of the epithelium, and active cell proliferation of the papilloma is likely to be a cause of increased FDG uptake.

Extramedullary Plasmacytoma Arising From the Anterior Mediastinum.

Plasmacytomas are a localized proliferation of plasma cells in the bone marrow and soft tissue. Extramedullary plasmacytomas are rare and typically solitary plasma cell neoplasms originating from extraosseous organs and tissues. A 31-year-old woman was referred to our hospital with a rapidly growing abnormal shadow on a chest roentgenogram. Chest computed tomography showed that the lesion was located in the anterior mediastinum. She underwent surgery, and the tumor was diagnosed as an extramedullary plasmacytoma. She remains well 2 years postoperatively without recurrence. An extremely rare case of an anterior mediastinal extramedullary plasmacytoma is presented.

Clinical significance of circulating miR-25-3p as a novel diagnostic and prognostic biomarker in osteosarcoma.

BACKGROUND: Emerging evidence has suggested that circulating microRNAs (miRNAs) in body fluids have novel diagnostic and prognostic significance for patients with malignant diseases. The lack of useful biomarkers is a crucial problem of bone and soft tissue sarcomas; therefore, we investigated the circulating miRNA signature and its clinical relevance in osteosarcoma. METHODS: Global miRNA profiling was performed using patient serum collected from a discovery cohort of osteosarcoma patients and controls and cell culture media. The secretion of the detected miRNAs from osteosarcoma cells and clinical relevance of serum miRNA levels were evaluated using in vitro and in vivo models and a validation patient cohort. RESULTS: Discovery screening identified 236 serum miRNAs that were highly expressed in osteosarcoma patients compared with controls, and eight among these were also identified in the cell culture media. Upregulated expression levels of miR-17-5p and miR-25-3p were identified in osteosarcoma cells, and these were abundantly secreted into the culture media in tumor-derived exosomes. Serum miR-25-3p levels were significantly higher in osteosarcoma patients than in control individuals in the validation cohort, with favorable sensitivity and specificity compared with serum alkaline phosphatase. Furthermore, serum miR-25-3p levels at diagnosis were correlated with patient prognosis and reflected tumor burden in both in vivo models and patients; these associations were more sensitive than those of serum alkaline phosphatase. CONCLUSIONS: Serum-based circulating miR-25-3p may serve as a non-invasive blood-based biomarker for tumor monitoring and prognostic prediction in osteosarcoma patients.

[Thymic Hyperplasia with Carcinoembryonic Antigen Elevation;Report of a Case].

A 64-year-old man was found to have serum carcinoembryonic antigen(CEA) elevation while undergoing an examination for recurrent gastroenteritis. His past medical history included gastroenteritis, rheumatoid arthritis, and diabetes. Blood testing revealed an increased CEA level of 153.00 ng/ml( normal ≤ 5.00 ng/ml). Chest computed tomography scan revealed an abnormal soft tissue shadow measuring 5.7 × 1.2 × 7 cm in the anterior mediastinum. The soft tissue shadow in the anterior mediastinum was the only abnormality found by whole-body examination. The possibility of a malignant tumor could not be ruled out, and the surgery was performed. Histopathological examination of the specimen confirmed thymic hyperplasia, and immunohistochemical staining detected CEA-positive cells. Serum CEA level normalized at three months after surgery and also 2 years postoperatively.

A case of schwannoma of the mesoesophagus displaced from the left to the right of the posterior mediastinum.

Although schwannomas are the most common neurogenic tumors found in the thorax, schwannomas of the mesoesophagus are extremely rare. We report a case of an 80-year-old man having a tumor in contact with the esophagus in the left posterior mediastinum. A preoperative follow-up computed tomography scan showed tumor displacement from the left to the right of the posterior mediastinum. The patient underwent surgery, and the tumor was diagnosed as a schwannoma of the mesoesophagus. The tumor might have been displaced from the left to the right of the posterior mediastinum because it was located in the mesoesophagus.

Bronchial artery aneurysm suggested to be caused by metalic tracheal stent migration.

Occurrence of bronchial artery aneurysm is rare, and it has been detected in less than 1 % of all selective bronchial arteriography cases. Here, we present a case of a bronchial artery aneurysm caused by a tracheal stent migration. A 59-year-old man was operated on for esophageal cancer, where an esophageal-tracheal fistula occurred 1 week after operation. Surgical repair of the esophageal-tracheal fistula was performed using a muscle flap, but this not results in fistula closure. Consequently, a self-expanding covered metallic tracheal stent was implanted for rescue, and this resulted in fistula closure. After 1 year, there was frequent hemoptysis caused by migration of the stent. He was referred to our hospital where removal of the stent was planned. A sudden occurrence of massive bleeding from trachea occurred, and extracorporeal membrane oxygenation (ECMO) was used. Although removal of tracheal stent was performed successfully, the patient subsequently died from multi-organ failure. Post-mortem autopsy revealed that the massive bleeding is originated from the rupture of a bronchial artery aneurysm.

Minimally Invasive Spinopelvic Fixation for Unstable Bilateral Sacral Fractures.

STUDY DESIGN: Retrospective case series. OBJECTIVE: We present a minimally invasive spinopelvic fixation technique for unstable bilateral sacral fractures and describe a technical report. SUMMARY OF BACKGROUND DATA: Unstable sacral fractures are severe injuries with high mortality and morbidity due to pain and malunion. Galveston technique is useful for rigid fixation of an unstable sacral fracture. However, wound-related complications with this technique have been relatively common because of extensive contusion of the skin or poor blood supply after embolization. MATERIALS AND METHODS: There were 34 patients with unstable pelvic fractures between 2005 and 2012. We performed conventional open surgery between 2005 and 2009. Minimally invasive spinopelvic fixation was performed between 2009 and 2012. Minimally invasive technique needs 4 small, lateral incisions for percutaneous lumbar pedicle screw insertion. We pushed a pure titanium rod into the paravertebral muscle. RESULTS: The average surgical time was 345 minutes in the conventional fixation and 208 minutes with the minimally invasive fixation. The average intraoperative bleeding was 520 mL in the conventional fixation and 290 mL in minimally invasive fixation. When comparing deep wound infection, 3 of 8 (38%) patients who received conventional fixation had methicillin-resistant Staphylococcus aureus infections, whereas nobody who received the minimally invasive fixation acquired infection. Bony union was achieved in 15 of the 16 patients. CONCLUSIONS: In this study, minimally invasive spinopelvic fixation required a shorter surgical time, incurred less bleeding, and had a lower infection rate than fixation with the conventional Galveston technique.

Transuncovertebral joint screw placement: technical note.

PURPOSE: Although a C2 pedicle screw and a C1-2 transarticular screw are the most rigid anchors, these screws cannot be used in cases with bilateral high-riding vertebral arteries. The authors describe their recent experience using a novel method of C2-3 transuncovertebral joint screw placement for occipitocervical fixation. METHODS: A 67-year-old patient suffered myelopathy due to instability at C1-2. The patient had bilateral high-riding vertebral arteries that precluded the use of a C2 pedicle screw or a C1-2 transarticular screw. RESULTS: A C2-3 transuncovertebral joint screw was applied bilaterally under 3D navigation guidance. The patient's postoperative course was uneventful, and his neurological status improved after the surgery. Bony fusion was achieved after the surgery. CONCLUSIONS: This is the first report to describe the technique of transuncovertebral joint screw. Using a C2-3 transuncovertebral joint screw, a long screw could be used, and it provided an anchor at C3 and C2 from a posterior approach.

Rare Pulmonary Metastasis From Thyroid Mucosa-Associated Lymphoid Tissue Lymphoma.

Primary pulmonary lymphomas constitute up to 1% of all pulmonary malignancies. Patients with mucosa-associated lymphoid tissue (MALT) lymphoma represent approximately 90% of patients with primary pulmonary lymphoma. Most pulmonary MALT lymphomas are primary tumors. Pulmonary metastasis is extremely rare. A 65-year-old woman was diagnosed with a thyroid MALT lymphoma in 2008 and underwent total thyroidectomy, followed by chemotherapy. After 5 years of follow-up, she referred to our hospital with an abnormal shadow on a chest roentgenogram. She underwent video-assisted thoracoscopic surgery and was diagnosed with metastatic thyroid MALT lymphoma. Postoperatively, she was treated with chemotherapy, including rituximab, and is alive without recurrence.