Extraneural metastatic ependymoma: distant metastasis to the pleura, lungs, lymph nodes and bone.

Ependymomas are neuroepithelial tumours arising from ependymal cells surrounding the cerebral ventricles that rarely metastasise to extraneural structures. This spread has been reported to occur to the lungs, lymph nodes, liver and bone. We describe the case of a patient with recurrent CNS WHO grade 3 ependymoma with extraneural metastatic disease. He was treated with multiple surgical resections, radiation therapy and salvage chemotherapy for his extraneural metastasis to the lungs, bone, pleural space and lymph nodes.

Tebentafusp in the treatment of metastatic uveal melanoma - the first patient treated in the Czech Republic.

BACKGROUND: Uveal melanoma is a rare cancer, in which metastases occur in approximately one half of cases. In metastatic disease, the prognosis is unfavorable and the median of survival does not exceed 6 months. Effective treatment options were very limited up to date. Tebentafusp is a bispecific fusion protein, which as the first drug proved efficacy in uveal melanoma. CASE: The patient was referred for suspected uveal melanoma of the left eye. She was treated for Hodgkin's disease in the past. Primarily, the tumor was treated by radiosurgery with radiotherapy of a small lesion of the vertebral body. However, later the patient had to undergo bulbus enucleation with confirmation of a large tumor category pT4b. PET/CT revealed metastases of the bones and the liver; simultaneously, haplotype A*02: 01 was confirmed. The patient underwent radiotherapy of the sternum and later, after confirmation of payment from the health insurance company, she started treatment with tebentafusp. The first three doses were administered during admission to the hospital, with a need to treat cytokine release syndrome by corticosteroids. Later, the administration was performed in an out-patient regimen, without complications, except for a transient elevation of transaminases. The first CT restaging confirmed stable disease; however, the second restaging confirmed a new osteolytic lesion in the processus of Th11. Because of progression, the treatment with tebentafusp was withdrawn after 6 months. Unfortunately, the lesion could not be treated by radiotherapy. Two months later, the patient was urgently admitted to the hospital because of right-sided hemiplegia; MRI revealed bleeding metastatic lesion in the brain stem. CONCLUSION: In this case report, we present the case of the first patient treated with this drug in the Czech Republic.

Diagnostic accuracy of contrast-enhanced computed tomography in assessing bone invasion in patients with oral squamous cell carcinoma.

OBJECTIVES: This study aimed to evaluate the diagnostic accuracy of contrast-enhanced computed tomography (CT) in detecting bone invasion in oral squamous cell carcinoma (OSCC) patients and to explore clinicopathological factors associated with its reliability. MATERIALS AND METHODS: 417 patients underwent preoperative contrast-enhanced CT followed by radical surgery. The presence or absence of bone invasion served as the outcome variable, with histopathologic examination of the resection specimen considered the gold standard. Statistical analyses, comprising correlation analyses and the determination of sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV), were conducted. RESULTS: CT exhibited 76.85% sensitivity, 82.20% specificity, 47.14% PPV, and 89.67% NPV. False-positive and false-negative rates were 11.27% and 5.99%, respectively. Artifacts affected assessment in 44 patients, but not in those with bone invasion. Tumor size, depth of invasion (DOI), tumor localization at the upper jaw, lymphatic invasion, and perineural invasion correlated with incorrect identification of bone invasion (Chi-square, p < 0.05). CONCLUSIONS: Despite utilizing thin-section CT, notable false-positive and false-negative results persisted. Patients with T3 tumors, DOI ≥ 10 mm, or upper jaw tumors are at higher risk for misidentification of bone invasion. Combining multiple methods may enhance diagnostic accuracy, and the integration of artificial intelligence or tracking electrolyte disturbances by tumor depth profiling shows promise for further assessment of bone invasion before histopathology. CLINICAL RELEVANCE: Surgeons should consider these insights when planning tumor resection. Supplementary imaging may be warranted in cases with high risk factors for misidentification. Further methodological advancements are crucial for enhancing diagnostic precision.

Interrogating Estrogen Signaling Pathways in Human ER-Positive Breast Cancer Cells Forming Bone Metastases in Mice.

Breast cancer bone metastases (BMET) are incurable, primarily osteolytic, and occur most commonly in estrogen receptor-α positive (ER+) breast cancer. ER+ human breast cancer BMET modeling in mice has demonstrated an estrogen (E2)-dependent increase in tumor-associated osteolysis and bone-resorbing osteoclasts, independent of estrogenic effects on tumor proliferation or bone turnover, suggesting a possible mechanistic link between tumoral ERα-driven osteolysis and ER+ bone progression. To explore this question, inducible secretion of the osteolytic factor, parathyroid hormone-related protein (PTHrP), was utilized as an in vitro screening bioassay to query the osteolytic potential of estrogen receptor- and signaling pathway-specific ligands in BMET-forming ER+ human breast cancer cells expressing ERα, ERß, and G protein-coupled ER. After identifying genomic ERα signaling, also responsibility for estrogen's proliferative effects, as necessary and sufficient for osteolytic PTHrP secretion, in vivo effects of a genomic-only ER agonist, estetrol (E4), on osteolytic ER+ BMET progression were examined. Surprisingly, while pharmacologic effects of E4 on estrogen-dependent tissues, including bone, were evident, E4 did not support osteolytic BMET progression (vs robust E2 effects), suggesting an important role for nongenomic ER signaling in ER+ metastatic progression at this site. Because bone effects of E4 did not completely recapitulate those of E2, the relative importance of nongenomic ER signaling in tumor vs bone cannot be ascertained here. Nonetheless, these intriguing findings suggest that targeted manipulation of estrogen signaling to mitigate ER+ metastatic progression in bone may require a nuanced approach, considering genomic and nongenomic effects of ER signaling on both sides of the tumor/bone interface.

Cinobufotalin Capsule Combined with Zoledronic Acid in the Treatment of Pain Symptoms and Clinical Efficacy in Prostate Cancer Patients with Bone Metastases: A Retrospective Study.

OBJECTIVE: To retrospectively analyse the effects of cinobufotalin capsule combined with zoledronic acid on pain symptoms and clinical efficacy of prostate cancer patients with bone metastases. METHODS: Patients with prostate cancer with bone metastasis admitted to our hospital from January 2021 to December 2022 were selected as study subjects. They were divided into the control group (treated with zoledronic acid) and the combined group (cinobufotalin capsules were added on the control group basis) according to different recorded treatment methods. The efficacies of the two groups after matching, lumbar L1-4 bone mineral density (BMD), serum calcium, serum phosphorus, visual analogue scale (VAS) score and Karnofsky performance status (KPS) score before and after treatment were compared, and adverse reactions were statistically analysed. RESULTS: A total of 102 patients were included in the study, encompassing 52 patients in the combined group and 50 patients in the control group. After 1:1 preference score matching, 64 patients were included in the two groups. No significant difference in baseline data was found between the two groups (p > 0.05). The total effective rate of the combination group was higher than that of the control group (p < 0.05). No significant differences in L1-4 bone mineral density, serum calcium and phosphorus, VAS score and KPS score were observed between the two groups prior to treatment (p > 0.05). After treatment, the L1-4 bone mineral density (BMD) and KPS score of the combined group decreased to less than those of the control group, the VAS score was lower than that of the control group, and the serum calcium and phosphorus level increased but less than that of the control group (p < 0.05). No significant difference in adverse reactions was found between the two groups (p > 0.05). CONCLUSIONS: Cinobufotalin capsule combined with zoledronic acid had ideal efficacy in the treatment of prostate cancer in patients with bone metastasis. This approach could improve their bone density and quality of life, improve their calcium and phosphorus metabolism, reduce their pain symptoms and provide increased safety. It may have an important guiding role in formulating future clinical treatment plans for patients with prostate cancer and bone metastasis.

Manubriectomy made easy.

Bone metastasis is the most common form of distant metastasis encountered within the breast cancer population. Surgical resection of bone metastases is a curative treatment option in patients who present with an isolated solitary lesion and no other associated disease. This decision is typically made following a multidisciplinary discussion. Patients can also be put forward for surgical excision of bone metastases following inadequate response to chemotherapy or radiotherapy.  With tumours located in the manubrium of the sternum, surgery serves not only to resect the bone metastasis but to provide suitable chest wall reconstruction. The goal of this approach is to maintain the structural and bony stability of the chest wall as well as that of associated structures, e.g. rib insertion or articulation of the shoulder girdle. A widely utilized approach involves excising the area of metastasis within the manubrium followed by implanting a bone cement prosthesis. Titanium plates are used to fix the bone prosthesis to the sternal body inferiorly and to the remainder of the manubrium superiorly.  We present a step-by-step video tutorial for performing a lower hemi-manubriectomy in a patient with triple-negative breast cancer. Our goal is to describe the fundamental principles and surgical techniques used to perform this procedure followed by the postoperative outcomes.

[Aprospective study of detection and clinical significance of bone marrow tumor cells in small cell lung cancer].

Objective: To investigate the detection of bone marrow tumor cells in small cell lung cancer (SCLC) patients and their relationship with clinical features, treatment response and prognosis. Methods: A total of 113patients with newly diagnosed SCLC from January 2018 to October 2022 at Beijing Chest Hospital were prospectively enrolled. Before treatment, bone marrow was aspirated and separately submitted for tumor cells detection by liquid-based cytology and disseminated tumor cells (DTCs) detection by the substrction enrichment and immunostaining fluorescence in situ hybridization (SE-iFISH) platform. The correlation between the detection results of the two methods with patients' clinical features and treatment response was evaluated by Chi-square. Kaplan-Meier method was applied to create survival curves and the Cox regression model was used for multivariate analysis. Results: The positive rate of bone marrow liquid-based cytology in SCLC was 15.93% (18/113). The liver and bone metastases rates were significantly higher (55.56% vs 11.58% for liver metastasis, P＜0.001; 77.78% vs 16.84% for bone metastasis, P＜0.001) and thrombocytopenia was more common (16.67% vs 2.11%, P=0.033) in patients with tumor cells detected in liquid-based cytology than those without detected tumor cells. As for SE-iFISH, DTCs were detected in 92.92% of patients (105/113), the liver and bone metastasis rates were significantly higher (37.93% vs 11.90% for liver metastasis, P=0.002; 44.83% vs 20.23 % for bone metastasis, P=0.010), and the incidence of thrombocytopenia was significantly increased (13.79% vs 1.19%, P=0.020) in patients with DTCs≥111 per 3 ml than those with DTCs＜111 per 3 ml. The positive rates of bone marrow liquid-based cytology in the disease control group and the disease progression group were 12.00% (12/100) and 46.15% (6/13), respectively, and the difference was statistically significant (P=0.002). However, the result of SE-iFISH revealed the DTCs quantities of the above two groups were 29 (8,110) and 64 (15,257) per 3 ml, and there was no statistical difference between the two groups (P=0.329). Univariate analysis depicted that the median progression-free survival (PFS) and median overall survival (OS) of liquid-based cytology positive patients were significantly shorter than those of tumor cell negative patients (6.33 months vs 9.27 months for PFS, P=0.019; 8.03 months vs 19.50 months for OS, P=0.019, P=0.033). The median PFS and median OS in patients with DTCs≥111 per 3 ml decreased significantly than those with DTCs＜111 per 3 ml (6.83 months vs 9.50 months for PFS, P=0.004; 11.2 months vs 20.60 months for OS, P=0.019). Multivariate analysis showed that disease stage (HR=2.806, 95%CI:1.499-5.251, P=0.001) and DTCs quantity detected by SE-iFISH (HR=1.841, 95%CI:1.095-3.095, P=0.021) were independent factors of PFS, while disease stage was the independent factor of OS (HR=2.538, 95%CI:1.169-5.512, P=0.019). Conclusions: Both bone marrow liquid-based cytology and SE-iFISH are clinically feasible. The positive detection of liquid-based cytology or DTCs≥111 per 3 ml was correlated with distant metastasis, and DTCs≥111 per 3 ml was an independent prognostic factor of decreased PFS in SCLC.

[Clinical characteristics and prognosis analysis of gastric cancer patients with bone metastasis].

Objectives: To investigate the clinical characteristics and prognosis of bone metastasis of gastric cancer, analyze the influencing factors of bone metastasis and the effects of different treatment methods, and provide a basis for early detection and treatment optimization of bone metastasis of gastric cancer. Methods: A total of 142 gastric cancer patients with bone metastasis admitted to the First Hospital of Lanzhou University from January 2011 to December 2021 were enrolled, including 60 cases of simple bone metastasis and 82 cases of bone metastasis combined with extraosseous metastasis. 142 patients with stage Ⅲgastric cancer without distant metastasis and 142 gastric cancer patients with visceral metastasis admitted to this hospital during the same period were also enrolled for comparison. Logistic regression analysis was used to determine the influencing factors of bone metastasis, and the Cox proportional hazards regression model was used to evaluate the influencing factors of overall survival (OS) of patients with bone metastasis. Results: Among the 142 patients with bone metastasis, poorly differentiated adenocarcinoma was the main type (123 cases), and 45 patients had simultaneous bone metastasis. Rib metastasis (100 cases), spine metastasis (88 cases), and pelvis metastasis (84 cases) were more common. A total of 110 patients had multiple bone metastasis, and 82 patients had extraosseous metastasis. Results of the stage Ⅲ gastric cancer group, the visceral metastasis group, the bone metastasis group, and the bone metastasis with extraosseous metastasis group were compared. There were significant differences in age, degree of differentiation, Borrmann type, alkaline phosphatase, lactate dehydrogenase, serum calcium, alanine aminotransferase, aspartate aminotransferase, creatine kinase isoenzyme, lymphocyte, hemoglobin, platelet, CEA, CA19-9, and CA724 (all P<0.05). Multivariate logistic regression analysis showed that Borrmann type was an independent protective factor of bone metastasis of gastric cancer (type 3: OR=0.07, 95%CI: 0.01-0.64, P=0.018). Alkaline phosphatase (OR=2.54, 95% CI: 1.07-6.01, P=0.034), serum calcium (OR=2.71, 95% CI: 1.15-6.41, P=0.023), creatine kinase isoenzyme (OR=16.33, 95% CI: 1.83-145.58, P=0.012), platelet (OR=10.08, 95% CI:1.89-53.85, P=0.007), and CA19-9 (OR=2.40, 95% CI: 1.14-5.05, P=0.021) were independent risk factors of bone metastasis of gastric cancer. The median OS of the stage Ⅲ gastric cancer group, the visceral metastasis group, the bone metastasis group, and the bone metastasis with extrabony group were 47, 13, 18, and 6 months, respectively, and the difference was statistically significant (P<0.001). The median OS of patients with bone metastasis only who underwent primary tumor surgery was 33 months, better than 6 months of patients without surgery (P=0.048). Multivariate Cox regression analysis showed that extraosseous metastasis (HR=2.45, 95% CI: 1.56-3.85, P<0.001) and decreased hemoglobin (HR=1.54, 95%CI: 1.02-2.34, P=0.042) were independent risk factors of OS of gastric cancer patients with bone metastasis. Conclusions: The prognosis of gastric cancer patients with bone metastasis alone is significantly better than that of other stage Ⅳ patients. For such patients, surgery on the primary site combined with chemotherapy after full evaluation may prolong the survival time.

Development of a precision tumor bone metastasis model by a magnetic micro-living-motor system.

An ideal bone metastasis animal model is critical and fundamental for mechanistic research and following development of new drug and treatment. Caudal artery (CA) injection allows bone metastasis in the hindlimb, while in-depth targeted and quantitative studies of bone metastasis require a new model to overcome its limitations. Here, we developed a targeted, quantitative, and highly consistent method for the modeling of bone metastasis with cell-based magnetic micro-living-motor (MLM) system created by effectively combining Fe3O4-PDA-Au with biosafety. The MLM system can achieve efficient migration, target site colonization and control tumorigenesis in bone precisely with the application of a magnetic field. In vivo, day 3 post cell injection, tumor bone metastasis signals were observed locally in the injected femur among 82.76% mice of the MLM group as compared to the 56.82% in the CA group, and the signal intensity was 45.1 and 95.9 times stronger than that in the left and right lower limbs of the CA group, respectively. Post-injection day 28, metastasis in vital organs was reduced by approximately 90% in the MLM group compared to the CA group. Our innovative use of the MLM system in the field of tumor modeling opens a new avenue for exploring the mechanisms of tumor bone metastasis, recurrence and drug resistance.

Effects of palliative intrathecal analgesia on patients with refractory cancer bone pain.

This study examined the effects of intrathecal analgesia (ITA) using an extracorporeal pump with a subcutaneous port system in cancer patients with bone metastasis. Among the patients who died of cancer with bone metastasis at the palliative care unit of our institution, 11 who received ITA were selected. Changes in pain, opioid doses, the palliative prognostic index (PPI), and Eastern Cooperative Oncology Group Performance Scale　after ITA were assessed. Pain, opioid doses, and PPI decreased after ITA (P = 0.002, 0.002, and 0.017). ITA for cancer patients with increased PPI due to refractory cancer bone pain decreased pain, opioid doses, and PPI.(100 words).

Optimizing PSMA scintigraphy for resource limited settings - a retrospective comparative study.

BACKGROUND: PSMA PET/CT is the most sensitive molecular imaging modality for prostate cancer (PCa), yet much of the developing world has little or no access to PET/CT. [99mTc]Tc-PSMA scintigraphy (PS) is a cheaper and more accessible gamma camera-based alternative. However, many resource-constrained departments have only a single camera without tomographic or hybrid imaging functionality, and camera time is frequently in high demand. Simplifying imaging protocols by limiting the field of view (FOV) and omitting SPECT/CT or even SPECT may provide a partial solution. The aim was thus to determine the adequacy of PS planar-only and/or SPECT-only imaging protocols with a limited FOV. METHODS: The scans of 95 patients with histologically proven PCa who underwent PS with full-body planar and multi-FOV SPECT/CT were reviewed. The detection rates for uptake in the prostate gland/bed and in metastases were compared on planar, SPECT, and SPECT/CT. The agreement between modalities was calculated for the detection of metastases and for staging. The impact of imaging a limited FOV was determined. RESULTS: Pathological prostatic uptake was seen in all cases on SPECT/CT (excluding two post-prostatectomy patients), 90.3% of cases on SPECT, and 15.1% on planar images (p < 0.001). Eleven (11.7%) patients had seminal vesicle involvement on SPECT/CT, which was undetectable/indistinguishable on planar images and SPECT. The agreement between modalities was moderate to good (κ = 0.41 to 0.61) for the detection of nodal metastases, with detection rates that did not differ significantly (SPECT/CT = 11.6%, SPECT = 8.4%, planar = 5.3%). Detection rates for bone metastases were 14.7% (SPECT/CT) and 11.6% (SPECT and planar). Agreement between modalities for the detection of bone metastases was good (κ = 0.73 to 0.77). Three (3.1%) patients had visceral metastases on SPECT/CT, two of which were detected on SPECT and planar. There was good agreement between modalities for the TNM staging of patients (κ = 0.70 to 0.88). No metastatic lesions were missed on the limited FOV images. CONCLUSION: When PS scintigraphy is performed, SPECT/CT is recommended. However, the lack of SPECT/CT capabilities should not preclude the use of PS in the presence of limited resources, as both planar and SPECT imaging are adequate and will correctly stage most PCa patients. Furthermore, time-based optimisations are achievable by limiting the FOV to exclude the distal lower limbs.

Hepatocellular carcinoma and musculoskeletal system: A narrative literature review.

Musculoskeletal alterations in hepatocellular carcinoma (HCC) are less common than liver-related complications. However, they can significantly impact the quality of life and overall prognosis of patients with HCC. The main obstacle in the clinical assessment of HCC-induced musculoskeletal alterations is related to effective and timely diagnosis because these complications are often asymptomatic and unapparent during routine clinical evaluations. This narrative literature review aimed to provide a comprehensive overview of the contemporary literature related to the changes in the musculoskeletal system in patients with HCC, focusing on its clinical implications and underlying etiopathogenetic mechanisms. Osteolytic bone metastases are the most common skeletal alterations associated with HCC, which could be associated with an increased risk of low-trauma bone fracture. Moreover, previous studies reported that osteopenia, sarcopenia, and myosteatosis are associated with poor clinical outcomes in patients with HCC. Even though low bone mineral density and sarcopenia are consistently reported as reliable predictors of pretransplantation and post-transplantation mortality in HCC patients, these complications are frequently overlooked in the clinical management of patients with HCC. Taken together, contemporary literature suggests that a multidisciplinary approach is essential for early recognition and clinical management of HCC-associated musculoskeletal alterations to improve patient prognosis. Further research into the mechanisms and treatment options for musculoskeletal complications is warranted to enhance our understanding and clinical management of this aspect of HCC.

Sweet syndrome with peripheral neuropathy in a patient with metastatic clear cell renal cell carcinoma.

A female patient in her 70s with a newly diagnosed clear cell renal cell carcinoma (ccRCC) with osseous metastasis presented with sudden onset erythematous painful blistering skin lesions on the dorsum of both hands, with associated intermittent fever episodes. Blood tests showed elevated inflammatory marker levels (C reactive protein 257.8 mg/dL, leucocytes 17.79×109/L, with 94% neutrophils). Histologically, there was predominately neutrophil dermal infiltrate without leucocytoclastic vasculitis. The diagnostic criteria of Sweet syndrome were fulfilled. A week later, the patient developed abrupt left-hand palsy, which was confirmed as a medial and ulnar sensorimotor axonal peripheral neuropathy of paraneoplastic origin. The patient was prescribed a course of oral high-dose steroids, which significantly improved the skin lesions. The peripheral nerve palsy improved after 3 months. This case describes the two very rare concurrent paraneoplastic manifestations of ccRCC occurring simultaneously, which have been rarely reported.

Metastasis patterns and prognosis in young gastric cancer patients: A propensity score­matched SEER database analysis.

BACKGROUND: Whether young patients with metastatic gastric cancer (GC) had distinct metastasis patterns and survival outcomes from older patients remains controversial. The aim of the present study was to explore the metastasis patterns and prognostic factors in young patients and evaluate the survival outcome in comparison to their older counterparts. MATERIALS AND METHODS: We identified patients with metastatic GC in the surveillance, epidemiology, and end results (SEER) database from 2010 to 2015. The patients were divided into two groups based on age at diagnosis: younger (≤40 years old) and older (>40 years old). We employed the chi-squared test to compare the clinicopathological characteristics between the two age groups. Furthermore, we conducted survival analyses using Kaplan-Meier and Cox regression analyses. To balance disparities in baseline characteristics, we employed propensity score matching (PSM). RESULTS: We identified 5,580 metastatic GC patients from the SEER database, with 237 (4.2%) classified as younger and 5343 (95.8%) as older patients. A total of 237 pairs of patients were generated after adjustment by PSM. Patients in the younger group exhibited a higher proportion of bone-only metastases and a lower proportion of liver-only metastases compared with patients in the older group. Multivariate Cox regression analysis demonstrated that youth was an independent protective factor for overall survival (OS) before and after PSM, but not for gastric cancer-specific survival (GCSS). Among the younger group, patients with liver-only metastasis demonstrated the best prognosis, whereas patients with lung-only metastasis exhibited significantly worse survival outcomes compared with liver-only metastases, even comparable to that of bone metastasis. CONCLUSIONS: Compared with the older group, the metastatic GC patients in the younger group exhibited more aggressive tumors but better prognoses. The metastasis pattern and its effect on the prognosis of GC varied by age group.

The Evaluation and Management of Lung Metastases in Patients with Giant Cell Tumors of Bone in the Denosumab Era.

Giant cell tumor of bone (GCTB) is characterized by uncertain biological behavior due to its local aggressiveness and metastasizing potential. In this study, we conducted a meta-analysis of the contemporary literature to evaluate all management strategies for GCTB metastases. A combination of the terms "lung metastases", "giant cell tumor", "bone", "treatment", and "oncologic outcomes" returned 133 patients meeting our inclusion criteria: 64 males and 69 females, with a median age of 28 years (7-63), at the onset of primary GCTB. Lung metastases typically occur at a mean interval of 26 months (range: 0-143 months) after treatment of the primary site, commonly presenting as multiple and bilateral lesions. Various treatment approaches, including surgery, chemotherapy, radiotherapy, and drug administration, were employed, while 35 patients underwent routine monitoring only. Upon a mean follow-up of about 7 years (range: 1-32 years), 90% of patients were found to be alive, while 10% had died. Death occurred in 25% of patients who had chemotherapy, whereas 96% of those not treated or treated with Denosumab alone were alive at a mean follow-up of 6 years (range: 1-19 years). Given the typically favorable prognosis of lung metastases in patients with GCTB, additional interventions beyond a histological diagnosis confirmation may not be needed. Denosumab, by reducing the progression of the disease, can play a pivotal role in averting or delaying lung failure.

Development of a New Focal Mouse Model of Bone Metastasis in Renal Cell Carcinoma.

BACKGROUND/AIM: Developing animal models of bone metastasis in renal cell carcinoma (RCC) is challenging as immunodeficient mice are required. The aim of this study was to develop a simple immune model of RCC bone metastasis. MATERIALS AND METHODS: RENCA tumor cells were injected into the right femurs of BALB/c mice. Sixty mice were grouped into each twenty-mouse group according to the tumor cell concentration, and the presence or absence and extent of bone metastasis in the total length of the femur were compared using hematoxylin and eosin staining of the excised tissues. RESULTS: Bone metastasis was significantly higher in the high concentration group than in the other groups (p<0.05), with 10 mice developing bone metastasis at two weeks and nine mice developing bone metastasis at three weeks. The extent of bone metastasis was significantly greater in the high concentration group than in the other groups (p<0.05). Multiple logistic regression analysis was performed to examine the factors influencing bone metastasis, and only the high concentration was a significant factor (p<0.05). CONCLUSION: We developed a normal immunity mouse model of local bone metastasis from RCC. This model could prove valuable for research into the treatment of bone metastases in RCC.

Establishment and validation of a nomogram for predicting overall survival of upper-tract urothelial carcinoma with bone metastasis: a population-based study.

BACKGROUND: Bone metastasis (BM) carries a poor prognosis for patients with upper-tract urothelial carcinoma (UTUC). This study aims to identify survival predictors and develop a prognostic nomogram for overall survival (OS) in UTUC patients with BM. METHODS: The Surveillance, Epidemiology, and End Results database was used to select patients with UTUC between 2010 and 2019. The chi-square test was used to assess the baseline differences between the groups. Kaplan-Meier analysis was employed to assess OS. Univariate and multivariate analyses were conducted to identify prognostic factors for nomogram establishment. An independent cohort was used for external validation of the nomogram. The discrimination and calibration of the nomogram were evaluated using concordance index (C-index), area under receiver operating characteristic curve (AUC), calibration curve, and decision curve analysis (DCA). All statistical analyses were performed using SPSS 23.0 and R software 4.2.2. RESULTS: The mean OS for UTUC patients with BM was 10 months (95% CI: 8.17 to 11.84), with 6-month OS, 1-year OS, and 3-year OS rates of 41%, 21%, and 3%, respectively. Multi-organ metastases (HR = 2.21, 95% CI: 1.66 to 2.95, P < 0.001), surgery (HR = 0.72, 95% CI: 0.56 to 0.91, P = 0.007), and chemotherapy (HR = 0.37, 95% CI: 0.3 to 0.46, P < 0.001) were identified as independent prognostic factors. The C-index was 0.725 for the training cohort and 0.854 for the validation cohort, and all AUC values were > 0.679. The calibration curve and DCA curve showed the accuracy and practicality of the nomogram. CONCLUSIONS: The OS of UTUC patients with BM was poor. Multi-organ metastases was a risk factor for OS, while surgery and chemotherapy were protective factors. Our nomogram was developed and validated to assist clinicians in evaluating the OS of UTUC patients with BM.

Osteocytes support bone metastasis of melanoma cells by CXCL5.

Bone metastasis is a common complication of certain cancers such as melanoma. The spreading of cancer cells into the bone is supported by changes in the bone marrow environment. The specific role of osteocytes in this process is yet to be defined. By RNA-seq and chemokines screening we show that osteocytes release the chemokine CXCL5 when they are exposed to melanoma cells. Osteocytes-mediated CXCL5 secretion enhanced the migratory and invasive behaviour of melanoma cells. When the expression of the CXCL5 receptor, CXCR2, was down-regulated in melanoma cells in vitro, we observed a significant decrease in melanoma cell migration in response to osteocytes. Furthermore, melanoma cells with down-regulated CXCR2 expression showed less bone metastasis and less bone loss in the bone metastasis model in vivo. Furthermore, when simultaneously down-regulating CXCL5 in osteocytes and CXCR2 in melanoma cells, melanoma progression was abrogated in vivo. In summary, these data suggest a significant role of osteocytes in bone metastasis of melanoma, which is mediated through the CXCL5-CXCR2 pathway.

Prognostic factors and real-life applicability of prognostic models for patients with bone metastases of carcinoma.

OBJECTIVE: This study aimed to investigate the factors affecting the survival of patients with bone carcinoma metastases and assess the clinical applicability of existing prognostic models. METHODS: We retrospectively evaluated 247 patients who presented to our hospital between 2011 and 2021 diagnosed with bone carcinoma metastasis. Demographic data, general health status, primary diagnoses, laboratory and radiological findings, pathological fracture status, treatment methods, and survival times of the patients were recorded, and the effects of these variables on survival time were evaluated. Previously developed Katagiri, Janssen, 2013-Spring, PathFX, and SORG prognostic models were applied, and the predictive performances of these models were evaluated by comparing the predicted survival time with the actual survival time of our patients. RESULTS: After the multivariate analysis, the following factors were shown to be significantly associated with the survival time of patients: blood hemoglobin and leukocyte levels, lactate dehydrogenase concentration, prognostic nutritional index, body mass index, performance status, medium and fast-growing groups of primary tumors, presence of extraspinal and visceral or brain metastases, and pathological fractures. According to receiver operating characteristics and Brier scores, SORG had the overall highest performance scores, while the Janssen nomogram had the lowest. CONCLUSION: Our report showed that all prognostic models were clinically applicable, but their performances varied. Among them, the SORG predictive model had the best performance scores overall and is the model the authors suggested for survival prediction among patients with carcinoma bone metastases. LEVEL OF EVIDENCE: Level IV, Prognostic Study.