Intramedullary nailing versus cemented plate for treating metastatic pathological fracture of the proximal humerus: a comparison study and literature review.

BACKGROUND: Pathological fracture of the humerus causes severe pain, limited use of the hand, and decreased quality of life. This study aimed to compare the outcomes of intramedullary nailing and locking plate in treating metastatic pathological fractures of the proximal humerus. METHODS: This retrospective comparison study included 45 patients (22 male, 23 female) with proximal humerus metastatic pathological fractures who underwent surgical treatment between 2011 and 2022. All data were collected from medical records and were analyzed retrospectively. Seventeen cases underwent intramedullary nailing plus cement augmentation, and 28 cases underwent locking plate plus cement augmentation. The main outcomes were pain relief, function scores, and complications. RESULTS: Among 45 patients with mean age 61.7 ± 9.7 years, 23 (51.1%) had multiple bone metastases, and 28 (62.2%) were diagnosed with impending fractures. The nailing group had significantly lower blood loss [100 (60-200) versus 500 (350-600) ml, p < 0.001] and shorter hospital stay (8.4 ± 2.6 versus 12.3 ± 4.3 days, p < 0.001) than the plating group. Average follow-up time of the nailing group was 12 months and 16.5 months for the plating group. The nailing group had higher visual analog scale (VAS) scores than the plating group, indicating greater pain relief with nailing [7 (6-8) versus 6 (5-7), p = 0.01]. Musculoskeletal Tumor Society functional scores [28 (27-29) versus 27 (26.5-28.5), p = 0.23] were comparable between groups. No complications, local recurrence, or revision surgery were reported until the last follow-up in either group. However, one case in the plating group had a humeral head collapse and fragmentation without needing revision surgery. CONCLUSIONS: Intramedullary nailing with cement augmentation is a viable option for treating proximal humerus metastatic pathological fracture, providing rigid fixation and better pain relief resulting in earlier mobility to optimize functional outcomes. Less invasive procedure with less blood loss and shorter hospital stay also benefits patients. Level of evidence Level II. Trial registration statement Not applicable.

Tumor-Specific Immunoenhancing Effects after Local Cryoablation for Metastatic Bone Tumor in a Mouse Model.

We investigated the abscopal effect after cryoablation (CA) on bone metastasis using a mouse model. Breast cancer cells were implanted in the bilateral tibiae of mice. The left tumor was treated locally with CA, and the right abscopal tumor (AT) was left untreated. The mice were divided into four groups based on the combination of CA and intraperitoneal administration of anti-PD-1 antibody (PD) as treatment interventions (Control, CA, PD, and CA + PD). The reduction ratio of the size of AT, the quantitative immune effects at enzyme-linked immunospot (ELISPOT) assay, and the intensity of infiltration of immune-related cells to AT were compared among the groups. CA alone showed a significant immunoenhancing effect on the volume change ratio of AT from day 0 to day 14 (Control-CA: p < 0.05), ELISPOT assay (Control-CA: p < 0.01), and CD4+ cell count in immunostaining (Control-CA: p < 0.05). CA alone showed no significant immunoenhancing effect on CD8+ and Foxp3+ cell counts in immunostaining, but the combination of CA and PD showed a significant immunoenhancing effect (Control-CA + PD: p < 0.01 [CD8, Foxp3]). The results suggested that the abscopal effect associated with the local cryotherapy of metastatic bone tumors was activated by CA and enhanced by its combination with PD.

What's new in musculoskeletal oncology.

We reviewed the recent literature related to primary musculoskeletal tumors and metastatic bone tumors. With regard to primary bone tumors, computer navigation systems and three-dimensional-printed prostheses seem to be new treatment options, especially in challenging anatomical locations, such as the sacrum and pelvis. Regarding the treatment of giant cell tumor of bone, recent studies have suggested that denosumab administration is related to a higher local recurrence rate following curettage, but a lower local recurrence rate following en bloc resection. In addition, there was no difference in the local recurrence rate at five years after surgery between short-term and long-term denosumab therapy. With regard to soft tissue tumors, percutaneous cryoablation appears to be a new treatment option for extra-abdominal desmoid tumors, with encouraging results. Regarding soft tissue sarcomas, a negative surgical margin of < 1 mm is sufficient to control local recurrence. Pexidartinib seems to be a promising systemic therapy for the treatment of tenosynovial giant cell tumors for which surgery is not expected to improve the function of the affected limb. Finally, the life expectancy of patients is the most important factor in determining the optimal surgical procedure for patients with impending or pathological fractures of the long bone due to metastatic bone tumors. Elevated C-reactive protein level was found to be an independent poor prognostic factor at 1 year after surgery for long bone metastases.

Total talar replacement for metastatic pulmonary adenocarcinoma of the talus: A case report.

Talar metastases from malignant tumors are rare and poorly documented. Treatment requires gradual relief of pain and preservation of function, with a choice between palliative measures and surgery. This case indicates that total talar replacement is an effective intervention for localized talar metastases and highlights the importance of early intervention. A 48-year-old man was diagnosed with a pathologic talar fracture due to talar metastases was observed after 8 years of chemotherapy following a diagnosis of lung adenocarcinoma. Despite radiotherapy, the patient's activities of daily living (ADLs) deteriorated due to pain on walking, prompting a request for surgical intervention. Total talar replacement was performed, allowing the patient to begin full weight-bearing ambulation 2 weeks post-operatively. Total talar replacement appears to be an effective treatment for localized talar metastases and should be performed as early as possible.

Metastatic patellar bone tumor due to gastric cancer resembling a primary or secondary aneurysmal bone cyst: A case report.

INTRODUCTION AND IMPORTANCE: Patellar bone tumors are very rare, and most are benign or of intermediate type. In this report, we describe our experience of a metastatic patellar bone tumor caused by gastric cancer, which resembled a very rare primary or secondary aneurysmal bone cyst and review the literature. CASE PRESENTATION: A 65-year-old man presented with severe pain in the patellar region and marked limitation of the knee joint range of motion. He had a history of gastric cancer; however, epidemiological, clinical, and imaging findings led us to strongly suspect an aneurysm-like bone cyst. Thus, we performed bone tumor curettage and autologous artificial bone grafting without biopsy because of the severe pain. Pathology results showed gastric cancer metastasis; hence, patellectomy and patellar tendon augmentation with femoral fascia were performed. The Musculoskeletal Tumor Society (MSTS) score was taken postoperatively to assess pain and function. CLINICAL DISCUSSION: We experienced a very rare gastric cancer-related metastatic patellar bone tumor, which resembled a primary or secondary aneurysmal bone cyst in frequency and imaging findings. Patellectomy was ultimately performed, and the patient's MSTS score improved markedly. CONCLUSION: Despite its very low frequency, patellar metastatic bone tumors must be taken into account without being misled by the frequency or imaging findings and a biopsy should necessarily be performed.

Breast cancer cells expressing cancer-associated sialyl-Tn antigen have less capacity to develop osteolytic lesions in a mouse model of skeletal colonization.

Breast cancer is one of the most prevalent malignancies in women, and approximately 75-80% of patients with advanced breast cancer develop bone metastasis. Expression of the cancer-associated carbohydrate antigen sialyl-Tn (STn) in breast cancer is associated with a poor prognosis; however, involvement of STn in the development of metastatic bone lesions remains unclear. We investigated whether STn expression on breast cancer cells influences intraosseous tumor growth and bone response in mice models of skeletal colonization. STn-positive (STn+) breast cancer cells were generated by stable transfection of an expression vector encoding ST6GaLNAc I into the breast cancer cell line MDA-MB-231. Parental MDA-MB-231 cells not expressing STn antigen were used as STn-negative (STn-) breast cancer cells. Contrary to expectations, STn expression attenuated the development of destructive bone lesions in the in vivo mice models. An in vitro study demonstrated that STn expression impaired adhesion of MDA-MB-231cells to bone marrow stromal cells. This finding in vitro was also confirmed by another breast cancer cell line MCF-7. Cell adhesion to fibronectin and type I collagen was also impaired in STn+ MDA-MB-231 cells compared to that in STn- MDA-MB-231 cells, suggesting integrin dysfunction. Given that the integrin ß1 subunit is the main carrier of the STn epitope, it is likely that changes in glycan structure impaired the adhesive capacity of ß1 integrin in the bone environment, leading to attenuation of tumor cell engraftment. In conclusion, breast cancer cells expressing STn antigen had less capacity for skeletal colonization, possibly due to impaired adhesive capability.

Metastasis of Renal Cell Carcinoma to the Trapezium.

Solitary metastasis of a carcinoma to carpal bone is extremely rare. Metastases of renal cell carcinoma (RCC) usually occur in a multiple fashion and there has been no report to date of a solitary metastasis to trapezium from RCC. The tumor was excised and reconstructed with iliac bone transplantation. 2 years and 6 months after surgery, there is no local recurrence with minimal functional loss.

Cytotoxic effects of zoledronic acid-loaded hydroxyapatite and bone cement in malignant tumors.

Metastatic and primary bone tumors are malignant tumors affecting the skeleton. Although the prognosis of patients with these tumors has improved with the development of effective chemotherapy, the challenges of local recurrence, subsequent osteolysis, degradation of bone strength and unresectable tumors persist. Local control of these tumors is therefore a key strategy to address these limitations. The third-generation bisphosphonate (BP), zoledronic acid (ZOL), has been demonstrated to reduce osteoclasts and exhibited potent antitumor effects in a number of malignancies. Hydroxyapatite (HA) and polymethyl methacrylate (PMMA) bone cement are used in orthopedic surgery as bone graft substitutes, for implant arthroplasty and bone strengthening, and as a sustained-release system for drugs such as antibiotics. At present, the antitumor effects of ZOL-loaded HA in vitro or in vivo or of ZOL-loaded bone cement in vivo have not been described. Therefore, the present study assessed the effects of ZOL-loaded HA and bone cement in malignant tumor cells. The two materials exerted strong antitumor effects against osteosarcoma, fibrosarcoma, synovial sarcoma, renal cancer, prostate cancer and lung cancer cells upon releasing ZOL. The antitumor effects of ZOL-loaded HA were less potent compared with those of ZOL-loaded bone cement, possibly as BPs exhibit higher affinity to HA. ZOL-loaded bone cement also exerted antitumor effects against pulmonary metastases and primary lesions, without exhibiting systemic toxicity in vivo. These results demonstrate that these materials may be beneficial for the treatment of malignant bone tumors, including metastatic bone tumors. In addition, as these materials are already in clinical use, such applications may be easily implemented.

Real-time in vivo imaging of metastatic bone tumors with a targeted near-infrared fluorophore.

Tumors of the prostate or breast are particularly likely to metastasize to the bone, and early diagnosis of metastatic bone tumors is important for designing an effective treatment strategy. Imaging modalities for the detection of bone metastasis are limited, and radiation-based techniques are commonly used. Here, we investigated the efficacy of selective near-infrared (NIR) fluorescence detection of metastatic bone tumors and its role in the detection of bone metastasis in prostate and breast cancer cell lines and in a xenograft mouse model. A targeted NIR fluorophore was used to monitor metastatic bone tumors using a NIR fluorescence imaging system in real time, enabling the diagnosis of bone metastasis in vivo by providing the location of the metastatic bone tumor. The NIR fluorescence imaging technique using targeted NIR contrast agents is a potential tool for the early diagnosis of bone tumors.

Effects of letrozole on breast cancer micro-metastatic tumor growth in bone and lung in mice inoculated with murine 4T1 cells.

Breast cancer (BC) is the leading cancer in women worldwide. Metastasis occurs in stage IV BC with bone and lung being common metastatic sites. Here we evaluate the effects of the aromatase inhibitor letrozole on BC micro-metastatic tumor growth in bone and lung metastasis in intact and ovariectomized (OVX) mice with murine estrogen receptor negative (ER-) BC cells inoculated in tibia. Forty-eight BALB/c mice were randomly assigned to one of four groups: OVX, OVX + Letrozole, Intact, and Intact + Letrozole, and injected with 4T1 cells intra-tibially. Letrozole was subcutaneously injected daily for 23 days at a dose of 1.75 µg/g body weight. Tumor progression was monitored by bioluminescence imaging (BLI). Following necropsy, inoculated tibiae were scanned via µCT and bone response to tumor was scored from 0 (no ectopic mineralization/osteolysis) to 5 (extensive ectopic mineralization/osteolysis). OVX mice had higher tibial pathology scores indicative of more extensive bone destruction than intact mice, irrespective of letrozole treatment. Letrozole decreased serum estradiol levels and reduced lung surface tumor numbers in intact animals. Furthermore, mice receiving letrozole had significantly fewer tumor colonies and fewer proliferative cells in the lung than OVX and intact controls based on H&E and Ki-67 staining, respectively. In conclusion, BC-inoculated OVX animals had higher tibia pathology scores than BC-inoculated intact animals and letrozole reduced BC metastases to lungs. These findings suggest that, by lowering systemic estrogen level and/or by interacting with the host organ, the aromatase inhibitor letrozole has the potential to reduce ER- BC metastasis to lung.

Evaluation of prognostic scoring systems for bone metastases using single-center data.

Recent progress in cancer treatment has improved patient survival, but has increased the number of patients with metastatic bone tumors. Data were collected from all bone metastasis patients at Kagoshima University, where almost all patients with metastatic bone tumors who reside in Kagoshima province are treated surgically. The scoring systems used in bone metastasis patients were then evaluated to identify those most suitable for our patients. Clinical data were collected from 145 patients with bone metastases. The patients were assigned prognostic scores based on four scoring systems, namely those described by the Ratasvuori, Mizumoto, Tokuhashi and Katagiri groups. Statistical examinations were performed to assess patient distribution regarding prognostic factors and the four data sets reported in the literature. The patient distributions for all prognostic factors were significantly different between the Scandinavian Sarcoma Group (SSG) and Kagoshima data. The distributions of patients for 3 of 5 and for 5 of 7 prognostic factors were statistically different between the Kagoshima data and the Katagiri and Tokuhashi data, respectively. Additionally, the distribution of patients in each scoring group was statistically different between the Kagoshima data and the Katagiri, Tokuhashi and Mizumoto data. The predictions of prognosis were significantly different between the results of each group and ours. The Tokuhashi scoring system detected the highest survival at 6 months (88.8%) in the Kagoshima data. Patients with a life expectancy of >6 months benefited from tumor excision and reconstruction. These findings suggest that the Tokuhashi scoring system is the most suitable for identifying patients who should be assessed for curative surgical intervention. SSG scoring, however, was suitable for identifying patients expected to survive for <6 months (91.3%). Prior to selecting a scoring system to predict prognosis, it is important to determine which scoring system is the most appropriate, based on each hospital's particular characteristics.

Metastatic bone tumors: Analysis of factors affecting prognosis and efficacy of CT and 18F-FDG PET-CT in identifying primary lesions.

We analyzed the prognostic factors in patients with metastatic bone tumors and evaluated the efficacy of different modalities in identifying the primary lesions. A total of 145 patients with bone metastases who attended the orthopaedic outpatient clinic were included in this study. The most frequent site of bone metastases was the spine. The primary tumor type was differently distributed between patients with a known primary tumor at the first visit and those with an unknown primary lesion. The number of breast cancer cases was statistically significantly lower in the primary-unknown group. However, the number of myeloma cases was significantly higher in the primary-unknown group. Survival was significantly lower in the skeletal-related events (SREs) compared to that in the non-SREs group. Furthermore, survival was significantly worse in patients with a performance status (PS) of ≥2 compared to those with a PS of ≤1 and neurological complications occurred statistically more often in the group with worse PS (≥2). Survival rates were significantly lower in the non-spinal compared to those in the spinal metastatic group. Since the majority of breast cancer patients presented with metastasis in the spine, a breast cancer origin was a positive prognostic factor in patients with spinal metastases. Although there were no significant differences between computed tomography (CT) and 18F-fluoro-2-deoxyglucose (18F-FDG) positron emission tomography (PET)-CT in detecting primary lesions, CT may be the first choice due to its feasibility. In conclusion, lung cancer, SREs and worse PS were adverse prognostic factors for patients with bone metastasis. In addition, CT scans may be more useful for determining the primary lesion of a bone metastasis compared to 18F-FDG PET-CT in a timelier manner.