Clinical research on zoledronic acid in treatment of pain caused by bone metastasis of malignant tumors

Objective:To evaluate the efficacy and safety of zoledronic acid for the pain caused by metastatic tumor of bone.Methods:52 patients with metastatic tumor of bone were randomly divided into two groups.The zoledronic acid group received 4 mg zoledronic acid infusion for 30 minutes and the control group received 90 mg pamidronate infusion for 6 hours. Results:The effective rates in zoledronic acid group and control group were 73.08%and 69.23%respectively.No significant difference was observed between the two groups.The median pain relief onset at days 5 and 7,respectively,and no significant difference was observed.The ECOG scores on the 7th day after medication:the differences in the zoledronic acid group before and after medication and between the two groups were both significant(P<0.001 and P=0.0448).The adverse reac- tion was no significant difference between the two groups.Conclusion:Zoledronic acid is efficient and safe in the treatment of pain caused by metastatic tumor of bone and it has low adverse reaction rate and convenient shorter using time.

Analysis of therapeutic efficacy of Aredia in treating pain caused by advanced malignant metastatic bone tumors

Objective To study therapeutic efficacy of Aredia in treating malignant metastatic bone tumors. Method 60～90 mg Aredia was administrated iv in 31 cases with malignant metastatic tumors,once each week. Results Pain in 12 cases was significantly relieved.14 cases acquired relif.Total effective rate was 83.9%.Activity ability was improved by 80.6%.No apparent toxicological and adverse effects as well as fever and cold symptoms were observed.Conclusion Aredia is a kind of ideal drugs for treatment of pain caused by malignant metastatic bone tumors.It is convenient in use and could be endured by patients.

Combined chemotherapy with Boning in the treatment of pain due to bone metasta ses from malignant tumors

Objective To investigate the effect of Boning o n pain due to bone metastases from mal ignant tumors.Method From De-cember,1998to December,2000,86pa tients with pathologically proved b one metastases from malignant tumors were randomly divided into two groups,study group(combined chemotherapy with boning),control group(simple chemotherapy).Boning(60mg )dissolved in saline solution(500ml )were given IV for consecutive 3days.Then 60mg Boning was given every half-month .Patients in control group accepted simple chemotherapy.Results Efficacy in study group was 88.37%which was significantly superior to th at in control group(66.47%).Boning could repair injured bone.Adverse r eaction associated with Boning was weak.Boning quickly relieved sympto ms for a long time.Conclusion Effect of large-dose Boning for reli eving pain due to bone metastases fro m malignant tumors is satisfying.At the same time,Boning play im-portant role in repair of destructed bone.

Prognostic factors in patients with bone metastasis of lung cancer after immune checkpoint inhibitors:A retrospective study

BACKGROUND Accurate data on the prognosis of bone metastases are necessary for appropriate treatment.Immune checkpoint inhibitors(ICIs)are widely used in the treatment of gene mutation-negative non-small cell lung cancer(GMN-NSCLC).AIM To investigate the prognostic factors in patients with bone metastases from GMNNSCLC following ICI use.METHODS This retrospective cohort study included 45 patients with GMN-NSCLC who were treated for bone metastases from 2017 to 2022 and received chemotherapy after diagnosis.Using Kaplan–Meier curves and Cox proportional hazards models,we evaluated the association between overall survival(OS)and clinical parameters,including serum biochemical concentrations and blood cell count.RESULTS Univariate analysis showed that Eastern Cooperative Oncology Group performance status≤1 and the use of ICIs and bone-modifying agents after bone metastasis diagnosis were significantly associated with a favorable OS.Multivariate analysis revealed that ICI use after bone metastasis diagnosis was signicantly associated with a favorable OS.CONCLUSION ICI use after bone metastasis diagnosis may be a favorable prognostic factor in patients with bone metastases of GMN-NSCLC.Consideration of ICI treatment for bone metastasis and GMN-NSCLC is warranted to establish a more accurate predictive nomogram for patients with bone metastasis.

High circulating tumor cell concentrations in a specific subtype of gastric cancer with diffuse bone metastasis at diagnosis

AIM: To clarify the biological feature contributing to gastric cancer with diffuse bone metastases at diagnosis.METHODS: The participants visited the Department of Clinical Oncology, Akita University Hospital, from January 2014 to August 2015. The selection criterion for gastric cancer with diffuse bone metastases at diagnosis includes over 29 hot spots of bone scintigraphy. Circulating tumor cell were collected from 20 m L of peripheral venous blood drawn using a Cell Search kit and a Cell Tracks Auto Prep system by SRL, a clinical laboratory. The endpoints of this study were correlations between circulating tumor cells(CTC) count and therapeutic outcomes. RESULTS: Among 39 patients with gastric cancer, 5 patients met the criterion. The incidence of this subtype was 12.8%. CTC counts ranged from 235 to 6440 cells/7.5 m L of peripheral blood(median of 1724). These values were much higher than common gastric cancers(2 cells). In chemo-sensitive cases, CTC counts decreased within 14 d(median) from 275, 235 and 1724 to 2, 7 and 66, respectively. On the other hand, CTC counts increased after treatment failure or insensitive case from 2, 7 and 6440 to 787, 513 and 7885, respectively. The correlation between CTC count and survival time showed a trend, but did not reach significance(Y = 234.6- 0.03 X, P = 0.085).CONCLUSION: High CTC count is a biological hallmark of this subtype, and can be used as a direct and definitive indicator of therapeutic outcome.

UNAMPUTATED TREATMENT FOR MALIGNANT BONE TUMOR AT LIMBS WITH INTERNAL RESECTION，CURETTAGE AND DEACTIVATION

A new operating programme was designed by us, based on keeping the whole limb in 1988. A successful operation on one patient with this new method was achieved on Dec. 17 in the same year at the First Teaching Hospital, Xi'an Medical Nniversity. Firstly, the internal tumor tissue was resected and curstted thoroughly, and the osseous shell was kept to attach to the normal bone tissue. Then, a plastic bag was used to encase the osseous shell in, deactivation was done with 95 per cent alcohol. the remainder osseous shell was used as a support, a pulp canal steel needle was inserted into it, and the bone cement was filled up in. In this way, a ' prosthesis' in pulp canal was formed, which was not only firm, reliable, less expensive convenient for drawing material, and satisfactory for achieving the goal of treating the tumor and keeping the limb, but also easy to move for the patient and to recover the function of the limb rapidly after operation because of not amputating the normal bone tissue and partly keeping the continuity of it. Now 25 cases have been treated with this new method, and in 90 per cent patients, the limbs have been preserved.

Limb salvage surgery for malignant bone tumors of the extremities in children and adolescents

Objective： The aim of the study was to analyze the clinical features of limb salvage surgery with epiphyseal preservation in children and adolescents, and to evaluate the recurrence rate, metastasis, complications, and the joint functional results after tumor resection. Methods： Between December 1995 and January 2003, 33 cases of preserving epiphysis procedure had been done. In this group, the tumor located in distal femur in 24 cases and in proximal tibia in 9 cases. There were 23 osteosarcomas, 6 Ewing＇s sarcomas, 2 chondrosarcomas, and 2 aggressive osteoblastomas. The patients received 2-4 cycles of preoperative adjuvant chemotherapy, and another 6 cycles after surgery. The modified protocol T10 was taken. Radiography and MRI were used to determine the margins of the tumors preoperatively and histological examination was used to corroborate the evidence intraoperatively. The tumors were staged clinically. Among them, there were 2 cases in ⅠA, 2 cases in ⅠB, 17 cases in ⅡA, and 12 cases in liB. According to the MRI analysis, the metaphyseal tumors in children were classified into 3 types. Type Ⅰ, with the tumor close to but not contacting epiphyseal plate, and the distance between the two over 2 cm, was taken as absolute indication for the technique. Type Ⅱ, with the tumor near or contacting epiphysis plate, and the distance between the two less than 1 cm, was taken as relative indication for the surgery. For type Ⅲ, the tumor contacted the epiphyseal plate partially, and was over 2 cm beyond the joint. In the cohort, 18 cases were categorized as type Ⅰ, 13 as type Ⅱ, and 2 as type Ⅲ. The size of the residual epiphyseal bone segment differed after different excision protocols which were taken according to the clinical classifications. Bone defects after tumor resections were repaired with massive intercalary allograft bone, followed by internal fixation by intramedullary nails and cancellous screws. Results： Among the 33 cases, 3 cases were lost to follow up. 29 cases had complete clinical data. Postoperative follow-up was 12-72 months. Recurrences were seen in 3 cases, with one local recurrence in type Ⅲ cases one year post tumor resection, other 2 recurrences around the femoral vessels in type Ⅱ cases 15 months and 30 months after the tumor resection respectively. The recurrence rate accounted for 10.34%. Amputation was performed for the cases with recurrences. But pulmonary metastasis developed and the patients died. In this cohort, 9 cases died. Five-year survival rate constituted 57.94% demonstrated by Kaplan-Meier survival analysis. The median survival time for male patients was 64.36 months, and that for female patients was 56.00 months （P = 0.0403）. The sites, stages and types were not associated with the survival time. Four cases reported 5 complications （17.24%）. The complications included fracture of the allograft, limb length discrepancy, nerve injury, breakage of nails, and loosening of the screws. No patient reported skin necrosis, hematoma, infection, rejection to the allograft, and nonunion at the end of the follow-up. According to the functional evaluation criteria after surgical treatment of malignant tumors of the extremities introduced by Enneking, excellent functional results were reported in 11 cases, good in 13 cases, fair in 3 cases, and poor in 2 cases. The excellent or good result rate was 83%. The excision interface involved partial epiphysis in 4 cases, involved the epiphyseal plate in 8 cases. Intact epiphysis was preserved in 17 cases. Five cases with poor postoperative functional results were in types II and III. Average time of bone union was 2.5 months for epiphyseal end and 3.8 months for diaphyseal end. According to the International Society of Limb Salvage （ISOLS） radiological implants evaluation system, excellent reconstruction was observed in 23 cases, good reconstruction in 4 cases, fair reconstruction in 1 case, and poor reconstruction in 1 case. All patients in the group had satisfactory joint stability. No patient reported joint dislocation, valgus or varus deformity, and osteoarthritis. The average limb length discrepancy was 3.2 cm, ranging 2-6 cm. Conclusion： The limb salvage surgery with preservation of epiphysis for malignant bone tumors in children and adolescents guarantees the patient＇s satisfactory postoperative limb functional results. Preoperative effective adjuvant chemotherapy and prevention of postoperative complications deserve great attention.

Clinicopathological Correlation of Primary Malignant Bone Tumors—An Observational Study

Background: Primary malignant tumors arising from bone are uncommon but important malignant neoplasms which account for 0.2% of all primary cancers in adults and approximately 5% of all childhood malignancies. Aim: No comprehensive surveillance data about primary malignant bone tumors is available from this region of West Bengal in the literature. An attempt is undertaken to correlate clinicopathological findings, both histological & cytological features of primary bone tumours. Method: This observational study of clinical presentation was corroborated with cytology and histopathology of 67 cases of primary malignant bone tumors in 2005-2007 in a tertiary health care centre. Results: Among the primary malignant tumors, 39 cases (58.20%) were male and 28 (41.80%) were female. Sixty one lesions (91%) were located in the long bones and 6 (9%) involving flat and short bones. Osteosarcomas are found to be the predominant primary malignant bone tumors (44.77%), followed by Ewing’s sarcomas (20.89%), chondrosarcomas (13.43%), high grade giant cell tumor, and plasmacytoma (5.97%). Predilection for male (M: F 2:1) found in both osteosarcoma and chondrosarcoma, but it was reverse in cases of Ewing’s sarcomas. Conclusion: Osteosarcoma is the most common around knee joint and chondrosarcoma is frequent in long bones in this region. We made an attempt to correlate FNAC findings with the histopathology and it was seen that overall sensitivity of FNAC of primary malignant bone tumors was 56.71%.

Malignant peripheral nerve sheath tumor with hemophilic syndrome and bone marrow fibrosis:A rare case report

BACKGROUND Malignant schwannoma is a rare tumor in the peripheral nervous system,accounting for approximately 5%to 10%of systemic soft tissue sarcomas.Especially,malignant schwannoma occurring in the broad ligament of the uterus with hemophilic syndrome and bone marrow fibrosis is extremely rare in clinical practice.Here,we report the first case of an patient diagnosed with malignant peripheral nerve sheath tumor(MPNST)of the broad ligament of the uterus with hemophilic syndrome and bone marrow fibrosis,and share our reference clinical diagnosis and treatment experience.CASE SUMMARY A patient was diagnosed with MPNST of the uterus harboring hemophilic syndrome and bone marrow fibrosis.She received combination,and repeated imaging revealed further encountered rare complications(hemophilia syndrome and bone marrow fibrosis)after two cycles of chemotherapy.Thereafter,combined treatment with pazopanib,gemcitabine,and dacarbazine was initiated.Unfortunately,the patient succumbed to death at hospital after two weeks.CONCLUSION This report firstly provided reference clinical practice for a patient with MPNST of the uterus harboring hemophilic syndrome and bone marrow fibrosis.Our case raises a reminder about the tolerance and safety of combination therapy,especially in young women.

Primary Malignant Giant Cell Tumor of Bone:A Case Report

Primary malignant giant cell tumor of bone is clinically rare,lack of specificity,and often misdiagnosed.Currently,related literature about this tumor remains scarce.One case of primary malignant giant cell tumor of bone was diagnosed and treated in our hospital,and the treatment effect was satisfactory.There was no recurrence or metastasis in 2 years of followup.The report is as follows.

Curcumin Inhibits Prostate Cancer Bone Metastasis by Up-Regulating Bone Morphogenic Protein-7 <i>in Vivo</i>

A number of studies have focused on the beneficial properties of Curcumin (diferuloyl methane, used in South Asian cuisine and traditional medicine) such as the chemoprevention of cancer. Recent studies have also indicated that this material has significant benefits for the treatment of cancer and is currently undergoing several clinical trials. We have been interested in the application of this compound as a therapeutic agent for advanced prostate cancer, particularly the skeletal complications in this malignancy. Our earlier work indicated that this compound could inhibit the osteomimetic properties which occur in castration resistant prostate cancer cells, by interfering with the common denominators between these cancer cells and the bone cells in the metastatic tumor microenvironment, namely the osteoblasts and the osteoclast. We predicted that curcumin could break the vicious cycle of reciprocal stimulation that results in uncontrolled osteolysis in the bony matrix. In this work, we have evaluated the potential of this compound in inhibiting the bone metastasis of hormone refractory prostate cancer cells in an established animal model. Our results strongly suggest that curcumin modulates the TGF-βsignaling that occurs due to bone matrix degradation by up-regulating the metastasis inhibitory bone morphogenic protein-7 (BMP-7). This enhancement of BMP-7 in the context of TGF-β in the tumor microenvironment is shown to enhance the mesenchymal-to-epithelial transition. Most importantly, we show that as a result of BMP-7 up-regulation, a novel brown/beige adipogenic differentiation program is also up-regulated which plays a role in the inhibition of bone metastasis. Our results suggest that curcumin may subvert the TGF-β signaling to an alternative adipogenic differentiation program in addition to the previously established interference with the osteomimetic properties, thus inhibiting the bone metastatic processes in a chemopreventive as well as therapeutic setting.

Mediastinal small cell carcinoma with liver and bone marrow metastasis, mimicking lymphoma

Primary mediastinal neuroendocrine tumors are a rare malignancy that accounts for < 10% of all mediastinal tumors. The case presented here involves a 52-yearold man who had been suffering for 3 mo from chronic cough, anorexia and substantial weight loss, as well as 2 wk of jaundice prior to his admission. A computed tomography scan showed a 4.3 cm × 6.6 cm mediastinal mass with multiple liver nodules scattered along both hepatic lobes. Endoscopic ultrasound showed a large heterogeneous hypoechoic mass at the mediastinum with multiple target-like nodules in the liver. Fine-needle aspiration specimens revealed numerous, small, round cells with hyperchromatic nuclei, scarce cytoplasm, and frequent mitotic features. Immunohistochemical study revealed positive results for AE1/AE3, CD56 and chromogranin A, with negative findings for synaptophysin, CK20, vimentin, CK8/18 and CD45. The patient was subsequently diagnosed with a poorly differentiated neuroendocrine carcinoma, small cell type. A bone marrow biopsy also revealed extensive involvement by the carcinoma.

U-Net Based Dual-Pooling Segmentation of Bone Metastases in Thoracic SPECT Bone Scintigrams

In order to enhance the performance of the CNN-based segmentation models for bone metastases, this study proposes a segmentation method that integrates dual-pooling, DAC, and RMP modules. The network consists of distinct feature encoding and decoding stages, with dual-pooling modules employed in encoding stages to maintain the background information needed for bone scintigrams diagnosis. Both the DAC and RMP modules are utilized in the bottleneck layer to address the multi-scale problem of metastatic lesions. Experimental evaluations on 306 clinical SPECT data have demonstrated that the proposed method showcases a substantial improvement in both DSC and Recall scores by 3.28% and 6.55% compared the baseline. Exhaustive case studies illustrate the superiority of the methodology.

Imaging appearance of bone tumors of the maxillofacial region

This paper reviews the imaging appearance of benign and malignant bone tumors of the maxillofacial region.A benign bone tumor commonly appears as a well circumscribed lesion.The matrix of the tumor may be calcified or sclerotic.Malignancies often display aggressive characteristics such as cortical breakthrough, bone destruction,a permeative pattern and associated soft-tissue masses.Computed tomography scan is an excellent imaging modality for accurate localization of the lesion,characterization of the tumor matrix and detection of associated osseous changes such as bone remodeling,destruction or periosteal reaction.Magnetic resonance imaging is of limited value in the evaluation of maxillofacial bone tumors.

Predictive Value of Clinical and Laboratory Parameters for Overt Bone Marrow Metastasis in Patients with Solid Malignancy

Bone marrow (BM) metastases are known to worsen the outcome in patients with malignancies and alter the choice of the treatment regimen. In an attempt to identify routine parameters for the prediction of BM metastasis we evaluated the clinical and laboratory data of 103 patients with metastatic solid tumors. We also assessed which of these factors appeared to influence survival. Three laboratory abnormalities were found to be predictive of metastasis on BM biopsy: thrombocytopenia 9/L OR 14.4;p = 0.02;hypocellular or dry tap aspirate OR 7.0;p = 0.02 and high serum alkaline phosphatase OR 6.5;p = 0.03. Three additional factors were found to be associated with deceased survival. Thrombocytopenia was associated with decreased survival from a median of 0.8 months to 4.1 months, p < 0.0001. Serum LDH levels more than twice the upper limit of normal were also reduced survival from 1.8 months versus 4.7 months, p = 0.03. Finally, the initial diagnosis of malignancy by bone marrow examination was associated with reduced survival from 1.8 months vs. 4.0 months, p = 0.03 in individuals where BM metastases were not the presenting feature of malignancies. Use of these simple clinical parameters may help in the early diagnosis of bone marrow metastases and improve clinical approach.

Urinary bladder malignant paraganglioma with vertebral metastasis:a case report with literature review

Paraganglioma is a rare neuroendocrine neoplasm observed in patients of all ages, with an estimated incidence of 3/1,000,000 population. It has long been recognized that some cases are familial. The majority of these tumors are benign, and the only absolute criterion for malignancy is the presence of metastases at sites where chromaffin tissue is not usually found. Some tumors show gross local invasion and recurrence, which may indeed kill the patient, but this does not necessarily associate with metastatic potential. Here, we report a case of vertebral metastatic paraganglioma that occurred 19 months after the patient had undergone partial cystectomy for urinary bladder paraganglioma. We believe this to be a rarely reported bone metastasis of paraganglioma arising originally within the urinary bladder. In this report, we also provide a summary of the general characteristics of this disease, together with progress in diagnosis, treatment, and prognosis.

Malignant giant cell tumors of the tendon sheath of the right hip:A case report

BACKGROUND Malignant giant cell tumor of the tendon sheath(MGCTTS)is an extremely rare malignant tumor originating from synovial and tendon sheath tissue with highly aggressive biological behavior and a high rate of local recurrence and distant metastasis which should be considered a highly malignant sarcoma and managed aggressively.How to systemically treat MGCTTS remains a challenge.In this case,a patient with MGCTTS suffered a recurrence after 2 surgical resections received adjuvant chemotherapy and radiation therapy,but the treatment outcome remained poor.More clinical trials and better understanding of the biology and molecular aspects of this subtype of sarcoma are needed while novel medicines should be developed to efficiently target particular pathways.CASE SUMMARY A 52-year-old man presented with persistent dull pain in the right groin accompanied by limited right hip motion starting 6 mo ago.Two months before his attending to hospital,the patient’s pain worsened,presenting as severe pain when standing or walking,limping,and inability to straighten or move the right lower extremity.Surgical excision was performed and MGCTTS was confirmed by pathology examination.Two recurrences occurred after surgical resection,moreover,the treatment outcome remained poor after adjuvant chemotherapy and radiation therapy.The patient died only 10 mo after the initial diagnosis.CONCLUSION MGCTTS is characterized by a joint mass with pain and limited motion.It typically grows along the tendons and infiltrated into the surrounding muscle and bone tissue,with a stubborn tendency to relapse,as well as pulmonary metastasis.Radically surgical resection provides a choice of treatment whereas post-operation care should be taken to preserve the function of the joint.Chemotherapy and radiotherapy can be used as alternative treatments when radical resection cannot be performed.

A nanoagent for concurrent therapy of breast cancer bone metastasis and cancer-induced bone pain through SLC7A11 interruption and photodynamic therapy

Bone metastasis,a life-threatening complication of advanced breast cancer,is often accompanied by debilitating pain(cancer-induced bone pain,CIBP)that severely impairs life quality and survival.The concurrent treatment of bone metastases and CIBP remains a clinical challenge because the therapeutic options are limited.In this study,we construct a near-infrared light-activated nano-therapeutic system to meet this conundrum.In detail,sorafenib(SRF)and photosensitizer(chlorin e6,Ce6)are encapsulated into mesoporous hydroxyapatite nanoparticles(HANPs),which are further functionalized with hyaluronic acid(HA)to obtain HA-SRF/Ce6@HANPs system.The designed nanoplatform destroys tumor cells in vitro and in vivo via the synergism of SRF(interrupting the exchange of cystine/glutamate by inhibiting SLC7A11)and photodynamic therapy(PDT,inducing reactive oxygen species generation).The decrease in tumor burden and reduction of extracellular glutamate significantly attenuate CIBP in mice model with developing bone cancer.Moreover,the combination of HA-SRF/Ce6@HANPs and PDT inhibit osteoclasts activation,promote osteoblast differentiation and accelerate bone repair.Overall,the nanoagent with good biocompatibility may provide an effective therapy method for the concurrent treatment of breast cancer bone metastasis and CIBP.

The Bone Microenvironmental Effect in the Dormancy of Cancer

Tumors have already threatened human life and health for centuries, especially the recurrent of bone metastases is difficult to cure. Relapse can occur years to decades after resection of primary tumor. This phenomenon is common in many clinical cases and animal experimental studies. The effect of traditional radiotherapy and chemotherapy on relapse is very limited, and the patients’ prognosis is poor. Because the delayed occurrence of metastases, researchers put forward a new concept “dormancy”, including a single dormant tumor cell (growth-arrest) and tumor mass dormancy (equivalence of the proliferation rate and apoptosis rate). It is probable that dormant tumor cells are the resource of relapse and the main reason of chemotherapy resistance. The mechanisms mediated tumor cell dormancy are complex and poorly understood, and bone marrow microenvironment plays an important role in this process. This review focuses on the bone marrow microenvironmental effect in inducing cancer cells to dormancy uncovered by the latest researches.