Development of End-to-End Artificial Intelligence Models for Surgical Planning in Transforaminal Lumbar Interbody Fusion.

Transforaminal lumbar interbody fusion (TLIF) is a commonly used technique for treating lumbar degenerative diseases. In this study, we developed a fully computer-supported pipeline to predict both the cage height and the degree of lumbar lordosis subtraction from the pelvic incidence (PI-LL) after TLIF surgery, utilizing preoperative X-ray images. The automated pipeline comprised two primary stages. First, the pretrained BiLuNet deep learning model was employed to extract essential features from X-ray images. Subsequently, five machine learning algorithms were trained using a five-fold cross-validation technique on a dataset of 311 patients to identify the optimal models to predict interbody cage height and postoperative PI-LL. LASSO regression and support vector regression demonstrated superior performance in predicting interbody cage height and postoperative PI-LL, respectively. For cage height prediction, the root mean square error (RMSE) was calculated as 1.01, and the model achieved the highest accuracy at a height of 12 mm, with exact prediction achieved in 54.43% (43/79) of cases. In most of the remaining cases, the prediction error of the model was within 1 mm. Additionally, the model demonstrated satisfactory performance in predicting PI-LL, with an RMSE of 5.19 and an accuracy of 0.81 for PI-LL stratification. In conclusion, our results indicate that machine learning models can reliably predict interbody cage height and postoperative PI-LL.

Myasthenia Gravis: Novel Findings and Perspectives on Traditional to Regenerative Therapeutic Interventions.

The prevalence of myasthenia gravis (MG), an autoimmune disorder, is increasing among all subsets of the population leading to an elevated economic and social burden. The pathogenesis of MG is characterized by the synthesis of autoantibodies against the acetylcholine receptor (AChR), low-density lipoprotein receptor-related protein 4 (LRP4), or muscle-specific kinase at the neuromuscular junction, thereby leading to muscular weakness and fatigue. Based on clinical and laboratory examinations, the research is focused on distinguishing MG from other autoimmune, genetic diseases of neuromuscular transmission. Technological advancements in machine learning, a subset of artificial intelligence (AI) have been assistive in accurate diagnosis and management. Besides, addressing the clinical needs of MG patients is critical to improving quality of life (QoL) and satisfaction. Lifestyle changes including physical exercise and traditional Chinese medicine/herbs have also been shown to exert an ameliorative impact on MG progression. To achieve enhanced therapeutic efficacy, cholinesterase inhibitors, immunosuppressive drugs, and steroids in addition to plasma exchange therapy are widely recommended. Under surgical intervention, thymectomy is the only feasible alternative to removing thymoma to overcome thymoma-associated MG. Although these conventional and current therapeutic approaches are effective, the associated adverse events and surgical complexity limit their wide application. Moreover, Restivo et al. also, to increase survival and QoL, further recent developments revealed that antibody, gene, and regenerative therapies (such as stem cells and exosomes) are currently being investigated as a safer and more efficacious alternative. Considering these above-mentioned points, we have comprehensively reviewed the recent advances in pathological etiologies of MG including COVID-19, and its therapeutic management.

Comparison Between Lumbar Endoscopic Unilateral Laminotomy for Bilateral Decompression and Other Decompression Approaches for Lumbar Spinal Stenosis: A Systematic Review.

BACKGROUND: Lumbar spinal stenosis affects numerous people globally. Full-endoscopic uniportal interlaminar decompression (FEUID) for lumbar spinal stenosis results in satisfactory outcomes. In this systematic review, we compared technical methods, surgical outcomes, and complications among different types of surgical techniques and discussed the effect of different surgical skill levels. METHODS: A systematic review of studies published from 1990 to January 2022 was performed. Studies related to FEUID were identified using the keywords "interlaminar decompression," "endoscopy," "uniportal," and "percutaneous." The outcomes measured were operative time, blood loss, hospital stay, complications, visual analog scale scores, Oswestry Disability Index scores, and the Macnab criteria. RESULTS: Ten of 306 studies were eligible for inclusion. For FEUID, data for 580 patients and more than 367 levels were collected. All the studies reported significant improvement in mean visual analog scale and Oswestry Disability Index scores, and the mean overall complication rate was 9.5%. Compared with other surgical techniques, FEUID resulted in lower visual analog scale and Oswestry Disability Index scores, complication rates, and blood loss and shorter hospital stay. These surgical parameters were considerably affected by a surgeon's skill level. CONCLUSION: FEUID results in better patient satisfaction with more favorable surgical outcomes and fewer complications. Although more prospective randomized controlled studies are required to confirm these findings, our results indicate that FEUID is a reasonable alternative to traditional lumbar spinal surgery.

Hypertrophic Ligamentum Flavum in Lumbar Spine Stenosis Is Associated With the Increased Expression of Secreted Protein Acidic and Rich in Cysteine.

STUDY DESIGN: Basic research. OBJECTIVES: Secreted protein acidic and rich in cysteine (SPARC) is a critical pro-fibrotic mediator. This study aims to characterize the role of SPARC in hypertrophic ligamentum flavum (LF) and fibrosis. METHODS: Hypertrophic LF samples were obtained from 8 patients with L4/5 lumbar spinal stenosis (LSS) during the decompressive laminectomy. Non-hypertrophic LF from age- and sex-matched 8 patients with L4/5 lumbar disc herniation was selected as control. An in vitro model of fibrosis in human LF cells was established by interleukin 6 (IL-6) to assess SPARC expression. RESULTS: Hypertrophic LF samples had higher fibrosis scores than control samples by Masson's trichrome staining (3.6 vs. 1.3, P < .001). Hypertrophic LF samples had significantly more positive staining for collagen and SPARC. Collagen III (Col3), α smooth muscle actin (α-SMA), and SPARC mRNA expression levels were significantly higher in hypertrophic LF samples than in control samples by qPCR. SPARC expression and fibrotic and inflammatory makers (collagen I, Col3, IL-6, interleukin 1ß) were significantly upregulated in IL-6 stimulation of normal LF in vitro. CONCLUSION: SPARC was detected in human LF and significantly upregulated in the clinical samples of hypertrophic LF compared to their normal counterparts. We also demonstrated an increased level of SPARC in an in vitro fibrosis model of LF. Thus, SPARC could be a crucial biomarker for the pathogenesis of hypertrophic LF and a therapeutic target for LSS.

Comparison of long-term outcomes of spinal fusion surgeries supplemented with "topping-off" implants in lumbar degenerative diseases: A systematic review and network meta-analysis.

Background Context: Spinal fusion surgery is a common treatment for lumbar degenerative diseases and has been associated with the long-term complication of adjacent segment disease (ASD). In recent years, the "topping-off" technique has emerged as a new surgical method, combining spinal fusion with a hybrid stabilization device (HSD) or interspinous process device (IPD) proximal to the fused vertebrae. Methods: A literature search using the PubMed, Cochrane Central Register of Controlled Trials, EMBASE, and Web of Science databases identified eligible studies comparing topping-off implant(s) with spinal fusion surgery for lumbar degenerative diseases. Risk of bias was assessed using the Cochrane RoB 2.0 tool for randomized controlled trials and the Newcastle-Ottawa scale for retrospective studies. Each outcome was analyzed using the statistical Confidence in NMA (CINeMA) 1.9.0 software. Results: 17 RCTs and retrospective studies that included 1255 participants and five interventions were identified. The topping-off implants device for intervertebral assisted motion (DIAM; OR = 0.235, p < 0.001), Dynesys (OR = 0.413, p < 0.001), and Coflex (OR = 0.417, p < 0.01) significantly lowered the incidence of radiographic adjacent segment degeneration (RASDeg) compared with spinal fusion surgery alone. Spinal fusion supplemented with DIAM significantly reduced the incidence of clinical adjacent segment disease (CASD) (OR = 0.358, p = 0.032). Conclusions: Spinal fusion supplemented with DIAM substantially reduced the incidence of radiographic and clinical adjacent segment disease. No significant difference was observed between the treatment comparators for reoperation due to ASD and back pain relief score.

High Accuracy and Safety of Intraoperative CT-Guided Navigation for Transpedicular Screw Placement in Revision Spinal Surgery.

BACKGROUND: Intraoperative CT-guided navigation (iCT-navigation) has been reported to improve the accuracy and safety of transpedicular screw placement in primary spinal surgery. However, due to a disrupted bony anatomy and scarring tissue, revision spinal surgery can be challenging. The purpose of this study was to evaluate the accuracy and safety of iCT-navigation for screw placement at the virgin site versus the revision site in revision thoracolumbar spinal surgery. METHOD: In total, 254 screws were inserted in 27 revision surgeries, in which 114 (44.9%) screws were inserted at the site with previous laminectomy or posterolateral fusion (the revision site), 64 (25.2%) were inserted at the virgin site, and 76 (29.9%) were inserted to replace the pre-existing screws. CT scans were conducted for each patient after all screws were inserted to intraoperatively confirm the screw accuracy. RESULTS: In total, 248 (97.6%) screws were considered accepted. The rate of accepted screws at the virgin site was 98.4% (63/64) versus 95.6% (109/114) at the revision site (p: 0.422). There were six (2.4%) unaccepted screws, which were immediately revised during the same operation. There was no neurological injury noted in our patients. CONCLUSION: With the use of iCT-navigation, the rate of accepted screws at the revision site was found to be comparable to that at the virgin site. We concluded that iCT-navigation could achieve high accuracy and safety for transpedicular screw placement in revision spinal surgery and allow for the immediate revision of unaccepted screws.

In Vitro and In Vivo Comparison of Bone Growth Characteristics in Additive-Manufactured Porous Titanium, Nonporous Titanium, and Porous Tantalum Interbody Cages.

Autogenous bone grafts are the gold standard for interbody fusion implant materials; however, they have several disadvantages. Tantalum (Ta) and titanium (Ti) are ideal materials for interbody cages because of their biocompatibility, particularly when they are incorporated into a three-dimensional (3D) porous structure. We conducted an in vitro investigation of the cell attachment and osteogenic markers of self-fabricated uniform porous Ti (20%, 40%, 60%, and 80%), nonporous Ti, and porous Ta cages (n = 6) in each group. Cell attachment, osteogenic markers, and alkaline phosphatase (ALP) were measured. An in vivo study was performed using a pig-posterior-instrumented anterior interbody fusion model to compare the porous Ti (60%), nonporous Ti, and porous Ta interbody cages in 12 pigs. Implant migration and subsidence, determined using plain radiographs, were recorded before surgery, immediately after surgery, and at 1, 3, and 6 months after surgery. Harvested implants were assessed for bone ingrowth and attachment. Relative to the 20% and 40% porous Ti cages, the 60% and 80% cages achieved superior cellular migration into cage pores. Among the cages, osteogenic marker and ALP activity levels were the highest in the 60% porous Ti cage, osteocalcin expression was the highest in the nonporous Ti cage, and the 60% porous Ti cage exhibited the lowest subsidence. In conclusion, the designed porous Ti cage is biocompatible and suitable for lumbar interbody fusion surgery and exhibits faster fusion with less subsidence compared with porous Ta and nonporous Ti cages.

Risk Factors for Spine Reoperation and Joint Replacement Surgeries after Short-Segment Lumbar Spinal Surgeries for Lumbar Degenerative Disc Disease: A Population-Based Cohort Study.

BACKGROUND: Short-segment lumbar spinal surgery is the most performed procedure for treatment of degenerative disc disease. However, population-based data regarding reoperation and joint replacement surgeries after short-segment lumbar spinal surgery is limited. METHODS: The study was a retrospective cohort design using the Taiwan National Health Insurance Research Database for data collection. Patients selected were diagnosed with lumbar degenerative disc disease and undergone lumbar discectomy surgery between 2002 and 2013. The Kaplan-Meier method was used to estimate the incidence of 1-year spine reoperation and joint replacement surgeries, and the Cox proportional hazard regression was used to examine risk factors associated with the outcomes of interest. RESULTS: A total of 90,105 patients were included. Incidences of 1-year spine reoperation and joint replacement surgeries for the hip and knee were 0.27, 0.04, and 0.04 per 100 people/month. Compared to fusion with the fixation group, fusion without fixation and the non-fusion group had higher risks of spine reoperation. Risk factors associated with spine reoperation included fusion without fixation, non-fusion surgery, age ≥ 45 years old, male gender, diabetes, a Charlson Comorbidity Index = 0, lowest social economic status, and steroid use history. Spine surgeries were not risk factors for joint replacement surgeries. CONCLUSIONS: Non-fusion surgery and spinal fusion without fixation had higher risks for spine reoperation. Spine surgeries did not increase the risk for joint replacement surgeries.

Timing of Bisphosphonate (Alendronate) Initiation after Surgery for Fragility Fracture: A Population-Based Cohort Study.

Bisphosphonates are used as first-line treatment for the prevention of fragility fracture (FF); they act by inhibiting osteoclast-mediated bone resorption. The timing of their administration after FF surgery is controversial; thus, we compared the incidence of second FF, surgery for second FF, and adverse events associated with early initiation of bisphosphonates (EIBP, within 3 months of FF surgery) and late initiation of bisphosphonates (LIBP, 3 months after FF surgery) in bisphosphonate-naïve patients. This retrospective population-based cohort study used data from Taiwan's Health and Welfare Data Science Center (2004-2012). A total of 298,377 patients received surgeries for FF between 2006 and 2010; of them, 1209 (937 EIBP and 272 LIBP) received first-time bisphosphonates (oral alendronate, 70 mg, once a week). The incidence of second FF (subdistribution hazard ratio (SHR) = 0.509; 95% confidence interval (CI): 0.352-0.735), second FF surgery (SHR = 0.452; 95% CI: 0.268-0.763), and adverse events (SHR = 0.728; 95% CI: 0.594-0.893) was significantly lower in the EIBP group than in the LIBP group. Our findings indicate that bisphosphonates should be initiated within 3 months after surgery for FF.

mTOR/EGFR/iNOS/MAP2K1/FGFR/TGFB1 Are Druggable Candidates for N-(2,4-Difluorophenyl)-2',4'-Difluoro-4-Hydroxybiphenyl-3-Carboxamide (NSC765598), With Consequent Anticancer Implications.

BACKGROUND: The application of computational and multi-omics approaches has aided our understanding of carcinogenesis and the development of therapeutic strategies. NSC765598 is a novel small molecule derivative of salicylanilide. This study aims to investigate the ligand-protein interactions of NSC765598 with its potential targets and to evaluate its anticancer activities in vitro. METHODS: We used multi-computational tools and clinical databases, respectively, to identify the potential drug target for NSC765598 and analyze the genetic profile and prognostic relevance of the targets in multiple cancers. We evaluated the in vitro anticancer activities against the National Cancer Institute 60 (NCI60) human tumor cell lines and used molecular docking to study the ligand-protein interactions. Finally, we used the DTP-COMPARE algorithm to compare the NSC765598 anticancer fingerprints with NCI standard agents. RESULTS: We identified mammalian target of rapamycin (mTOR)/epidermal growth factor receptor (EGFR)/inducible nitric oxide synthase (iNOS)/mitogen-activated protein 2 kinase 1 (MAP2K1)/fibroblast growth factor receptor (FGFR)/transforming growth factor-ß1 (TGFB1) as potential targets for NSC765598. The targets were enriched in cancer-associated pathways, were overexpressed and were of prognostic relevance in multiple cancers. Among the identified targets, genetic alterations occurred most frequently in EGFR (7%), particularly in glioblastoma, esophageal squamous cell cancer, head and neck squamous cell cancer, and non-small-cell lung cancer, and were associated with poor prognoses and survival of patients, while other targets were less frequently altered. NSC765598 displayed selective antiproliferative and cytotoxic preferences for NSCLC (50% growth inhibition (GI50) = 1.12-3.95 µM; total growth inhibition (TGI) = 3.72-16.60 µM), leukemia (GI50 = 1.20-3.10 µM; TGI = 3.90-12.70 µM), melanoma (GI50 = 1.45-3.59 µM), and renal cancer (GI50 = 1.38-3.40 µM; TGI = 4.84-13.70 µM) cell lines, while panels of colon, breast, ovarian, prostate, and central nervous system (CNS) cancer cell lines were less sensitive to NSC765598. Interestingly, NSC765598 docked well into the binding cavity of the targets by conventional H-bonds, van der Waal forces, and a variety of π-interactions, with higher preferences for EGFR (ΔG = -11.0 kcal/mol), NOS2 (ΔG = -11.0 kcal/mol), and mTOR (ΔG = -8.8 kcal/mol). NSC765598 shares similar anti-cancer fingerprints with NCI standard agents displayed acceptable physicochemical values and met the criteria of drug-likeness. CONCLUSION: NSC765598 displayed significant anticancer and potential multi-target properties, thus serve as a novel candidate worthy of further preclinical studies.

Functional outcomes of full-endoscopic spine surgery for high-grade migrated lumbar disc herniation: a prospective registry-based cohort study with more than 5 years of follow-up.

BACKGROUND: Full-endoscopic lumbar discectomy (FELD) is an alternative to posterior open surgery to treat a high-grade migrated herniated disc. However, because of the complexity of the surgery, success is dependent on the surgeon's skill. Therefore, patients are frequently treated using open discectomy. Anatomical constraints and technical difficulties can lead to the incomplete removal of high-grade migrated discs. METHODS: We retrospectively reviewed patients who had undergone FELD performed by a single surgeon between January 2010 and January 2014 from a prospective spine registry in an institute. Perioperative records and data of the Oswestry Disability Index, visual analog scale scores (preoperatively and 2 weeks, 6 weeks, 3 months, 6 months, 1 year, 2 years, and 5 years after the operation), and MacNab criteria were collected. RESULTS: Of 58 patients with a follow-up duration of > 5 years, (41 and 17 patients had undergone transforaminal endoscopic lumbar discectomy [TELD] and interlaminar endoscopic lumbar discectomy [IELD], respectively), the satisfaction rate was 87.8% (five unsatisfactory cases) for TELD and 100% for IELD. The overall percentage of patients with good to excellent results according to modified MacNab criteria was 91.3% (53/58 patients). Two patients had residual discs. Two patients needed an open discectomy due to recurrent disc herniation. One IELD patient received spinal fusion surgery due to segmental instability after 5 years. CONCLUSION: FELD has a high success rate for the management of high-grade migrated herniated discs. In patients with high-grade disc migration from L1 to L5, TELD is effective and safe. However, for L4-L5 and L5-S1 high-grade upward and downward disc migration, IELD is the favorable option and provides high patient satisfaction.

Uniportal Endoscopic Interlaminar Decompression in Lumbar Spinal Stenosis: A Comprehensive Review.

BACKGROUND: From the 1990s, there has been growth in the literature demonstrating the feasibility of minimally invasive approaches for treating variety lumbar spinal disorders. There is still much work to be done in overcoming the technical challenges and explicate relative advantages of endoscopic techniques in lumbar spine surgery. In this comprehensive literature review, we discuss the history, indications, contraindications, surgical techniques, learning curves, technical tips, adverse events, and examine peer-reviewed studies addressing uniportal endoscopic interlaminar decompression in lumbar spinal surgery. METHODS: This literature review was conducted with keywords "endoscopic," "minimally invasive," "uniportal endoscopic decompression," "interlaminar decompression," and "lumbar spinal surgery" using PubMed, Embase, ClinicalKey, and Google Scholar. RESULTS: Review of 423 patients who underwent uniportal endoscopic interlaminar lumbar decompression showed satisfying results with 82% of patients no longer having leg pain, and 13% of patients having only occasional pain, with no significant operation-related deterioration in leg or back pain. To compare the outcomes between endoscopic and microscopic technique, a comparative review of 192 lumbar lateral recess stenosis patients demonstrated the uniportal endoscopic group had 29% shorter operation duration, 1.2% fewer perioperative complications, and significantly reduced postoperative pain (visual analog scale) over 5 days, and reduced use of pain medications. Multiple retrospective studies echoed the outcomes of endoscopic decompression surgery, showed shorter hospitalization time, lower mean dural expansion, lower increment of horizontal displacement measured, and less elevated levels of postoperative serum CPK (creatine phosphokinase) and CRP (c-reactive protein). Lastly, a systematic review and meta-analysis that enrolled 994 patients found that patients who received the full-endoscopic decompression technique showed statistically lower levels of back pain and leg pain and a 40% lower chance of having complications compared with those receiving microscopic decompression in lumbar stenosis. CONCLUSIONS: Based on our literature review, there are multiple positive outcomes with endoscopic interlaminar lumbar decompression, which reduces operation duration, perioperative complications, and better postoperative outcomes. However, the technical challenge highlights the importance of further training and innovation in this rapidly evolving field.

Novel Insights into the Pathogenesis of Spinal Sarcopenia and Related Therapeutic Approaches: A Narrative Review.

Spinal sarcopenia is a complex and multifactorial disorder associated with a loss of strength, increased frailty, and increased risks of fractures and falls. In addition, spinal sarcopenia has been associated with lumbar spine disorders and osteoporosis, which renders making decisions on treatment modalities difficult. Patients with spinal sarcopenia typically exhibit lower cumulative survival, a higher risk of in-hospital complications, prolonged hospital stays, higher postoperative costs, and higher rates of blood transfusion after thoracolumbar spine surgery. Several studies have focused on the relationships between spinal sarcopenia, appendicular muscle mass, and bone-related problems-such as osteoporotic fractures and low bone mineral density-and malnutrition and vitamin D deficiency. Although several techniques are available for measuring sarcopenia, each of them has its advantages and shortcomings. For treating spinal sarcopenia, nutrition, physical therapy, and medication have been proven to be effective; regenerative therapeutic options seem to be promising owing to their repair and regeneration potential. Therefore, in this narrative review, we summarize the characteristics, detection methodologies, and treatment options for spinal sarcopenia, as well as its role in spinal disorders.

High Expression of Acid-Sensing Ion Channel 2 (ASIC2) in Bone Cells in Osteoporotic Vertebral Fractures.

Little is known about the function of acid-sensing ion channels (ASICs) in bone cells or osteoporotic vertebral fractures (OVF). This study delineated ASICs expression in adult human bone marrow-mesenchymal stem cells- (BM-MSC-) derived osteoblasts and in OVF bone cells. Adult BM-MSC-derived osteoblasts were isolated and cultured in different pH values. Osteogenic markers as alkaline phosphatase (ALP), osteopontin (OPN), and osteocalcin (OC) mRNA were assessed. Western blots method was applied to analyze ASICs protein expression in different pH values. Amiloride was added into the osteogenic media to analyze the Na+/K+ ATPase change. We harvested the vertebral cancellous bone through a bone biopsy needle in 26 OVF patients when performing percutaneous vertebroplasty. Six vertebral bone specimens obtained from 4 patients with high-energy vertebral fractures were used as the control. The reverse transcription polymerase chain reaction was performed to analyze the quantitative mRNA expression of ASICs. Osteogenic markers as ALP, OPN, and OC mRNA were higher expressed in increasing pH values throughout osteoblastogenesis. ASIC proteins were higher expressed in lower pH media, especially ASIC3, and ASIC4. The highest protein expression at days 7, 14, and 21 was ASIC2, ASIC4, and ASIC3, respectively. Expression of Na+/K+ ATPase was significantly decreased in cultured osteoblasts by addition of amiloride into the pH 6.9 osteogenic media. ASIC2 mRNA was most highly expressed with a 65.93-fold increase in the biopsied vertebral bone cells in OVF compared with the control. In conclusion, we found osteoblastogenesis was reduced in an acidic environment, and ASIC2, ASIC3, and ASIC4 were most highly expressed in turn during osteoblastogenesis within acidic media. ASIC2 was the most abundantly expressed gene in human bone cells in OVF compared with the control. ASIC2 could be crucial in the pathogenesis of osteoporosis and could serve as a therapeutic target for antiosteoporotic therapies.

Full-Endoscopic Lumbar Foraminoplasty for Symptomatic Cement Leakage with Exiting Nerve Root Impingement.

BACKGROUND: Foraminal stenosis, a common disorder occurring in elderly patients, is often caused by narrowing of the foramen, resulting in the confinement of neural structures by the tissue and vertebrae. Full-endoscopic lumbar foraminoplasty (FELF) is an effective treatment option for patients with foraminal stenosis. However, to the best of our knowledge, no previous study has reported the treatment of symptomatic cement leakage. We report a case of symptomatic cement leakage treated with FELF with the patient under local anesthesia. CASE DESCRIPTION: An 85-year-old woman was admitted to our spine unit because of lower back pain. The patient had presented with lower back pain and new-onset left thigh pain after vertebroplasty performed 3 months previously. The patient was not able to walk and was bedridden. To overcome this problem, T12 percutaneous vertebroplasty and left transforaminal L3-L4 foraminoplasty was performed with the patient under local anesthesia. After surgery, the patient was able to walk and was discharged 4 days postoperatively. CONCLUSION: The present report has shown that FELF can successfully remove symptomatic cement leakage, resulting in pain relief.

NaF PET/CT for response assessment of prostate cancer bone metastases treated with single fraction stereotactic ablative body radiotherapy.

INTRODUCTION: In prostate cancer patients, imaging of bone metastases is enhanced through the use of sodium fluoride positron emission tomography (18F-NaF PET/CT). This imaging technique shows areas of enhanced osteoblastic activity and blood flow. In this work, 18F-NaF PET/CT was investigated for response assessment to single fraction stereotactic ablative body radiotherapy (SABR) to bone metastases in prostate cancer patients. METHODS: Patients with bone metastases in a prospective trial treated with single fraction SABR received a 18F-NaF PET/CT scan prior to and 6 months post-SABR. The SUVmax in the tumour was determined and the difference between before and after SABR determined. The change in uptake in the non-tumour bone was also measured as a function of the received SABR dose. RESULTS: Reduction in SUVmax was observed in 29 of 33 lesions 6 months after SABR (mean absolute decrease in SUVmax 17.7, 95% CI 25.8 to - 9.4, p = 0.0001). Of the three lesions with increased SUVmax post-SABR, two were from the same patient and located in the vertebral column. Both were determined to be local progression in addition to one fracture. The third lesion (in a rib) was shown to be controlled locally but suffered from a fracture at 24 months. Progression adjacent to the treated volume was observed in two patients. The non-tumour bone irradiated showed increased loss in uptake with increasing dose, with a median loss in uptake of 23.3% for bone receiving 24 Gy. CONCLUSION: 18F-NaF PET/CT for response assessment of bone metastases to single fraction SABR indicates high rates of reduction of osteoblastic activity in the tumour and non-tumour bone receiving high doses. The occurrence of marginal recurrence indicates use of larger clinical target volumes may be warranted in treatment of bone metastases. TRIAL REGISTRATION: POPSTAR, 'Pilot Study of patients with Oligometastases from Prostate cancer treated with STereotactic Ablative Radiotherapy', Universal Trial Number U1111-1140-7563 , Registered 17th April 2013.

Cement-augmented pedicle screw insertion assisted by spinal robotic systems for widespread spinal metastases.

Widespread spinal metastases can obscure bone landmarks and severely hinder surgical safety during pedicle screw insertion. Robot-assisted spinal surgery has demonstrated an excellent safety profile for pedicle screw insertion. Moreover, spinal surgery robotic systems can facilitate pedicle screw insertion with high-accuracy. We present a patient who had breast cancer with widespread spinal metastases, pathological vertebral fracture, and spinal cord compression with a challenge of intraoperative image recognition. To overcome this problem, she received surgical decompression and stabilization through the insertion of cement-augmented pedicle screws with the assistance of a spinal robotic system. At the 1-year follow-up, no implant loosening was observed, and the patient exhibited notable physical improvements, demonstrating that cement-augmented pedicle screw insertion with the assistance of spinal robotic systems is an effective method for treating widespread spinal metastases.

MLN4924, a Protein Neddylation Inhibitor, Suppresses the Growth of Human Chondrosarcoma through Inhibiting Cell Proliferation and Inducing Endoplasmic Reticulum Stress-Related Apoptosis.

Chondrosarcoma, a heterogeneous malignant bone tumor, commonly produces cartilage matrix, which generally has no response to conventional therapies. Studies have reported that MLN4924, a NEDD8-activating enzyme inhibitor, achieves antitumor effects against numerous malignancies. In this study, the suppressive effects of MLN4924 on human chondrosarcoma cell lines were investigated using in vitro and in vivo assays, which involved measuring cell viability, cytotoxicity, apoptosis, proliferation, cell cycles, molecule-associated cell cycles, apoptosis, endoplasmic reticulum (ER) stress, and tumor growth in a xenograft mouse model. Our results demonstrated that MLN4924 significantly suppressed cell viability, exhibited cytotoxicity, and stimulated apoptosis through the activation of caspase-3 and caspase-7 in chondrosarcoma cell lines. Furthermore, MLN4924 significantly inhibited cell proliferation by diminishing the phosphorylation of histone H3 to cause G2/M cell cycle arrest. In addition, MLN4924 activated ER stress⁻related apoptosis by upregulating the phosphorylation of c-Jun N-terminal kinase (JNK), enhancing the expression of GRP78 and CCAAT-enhancer-binding protein homologous protein (CHOP, an inducer of endoplasmic ER stress⁻related apoptosis) and activating the cleavage of caspase-4. Moreover, MLN4924 considerably inhibited the growth of chondrosarcoma tumors in a xenograft mouse model. Finally, MLN4924-mediated antichondrosarcoma properties can be accompanied by the stimulation of ER stress⁻related apoptosis, implying that targeting neddylation by MLN4924 is a novel therapeutic strategy for treating chondrosarcoma.