Tumor- and Osteoblast-Derived Periostin in Prostate Cancer bone Metastases

Exploring the biological function of periostin (POSTN) in prostate cancer (PCa) bone metastasis is of importance. It was observed that the expression of POSTN was high in PCa, especially highest in PCa metastasized to bone. In this study, we found that inhibiting POSTN in PCa cells could significantly alleviate PCa bone metastasis in vivo, suggesting POSTN is a promising therapeutic target. Since, due to the secreted expression of POSTN in osteoblasts and PCa, we hypothesized the positive feedback loop between osteoblasts and PCa mediated by POSTN in PCa bone metastasis. The in vitro experiments demonstrated that osteoblast-derived POSTN promoted PCa cell proliferation and invasion and PCa cell-derived POSTN promotes proliferation of osteoblasts. Furthermore, we found that POSTN regulated PCa and osteoblast function through integrin receptors. Finally, 18F-Alfatide II was used as the molecule probe of integrin αvβ3 in PET-CT, revealing high intake in metastatic lesions. Our findings together indicate that targeting POSTN in PCa cells as well as in the osteoblastic may be an effective treatment for PCa bone metastasis.

Case Report: Prophylactic Plate Fixation for Incomplete Atypical Ulnar Fractures Resulting From the Use of Denosumab for Bone Metastases

Patients with bone metastases are treated with long-term bone resorption inhibitors such as bisphosphonates and denosumab. However, resorption inhibitors have been known to cause fractures, such as atypical femoral fractures (AFFs). In recent years, there have been an increasing number of reports of atypical ulna fractures (AUFs) caused by bone resorption inhibitor usage. Treatment of AUFs is complicated, especially when they occur in patients with bone metastases, because it is difficult to discontinue bone resorption inhibitor treatment without the risk of aggravating metastatic lesions. Prophylactic surgery is recommended in AFFs when fractures are predicted, but there are few reports of prophylactic surgery for AUFs. Here, we report a case of incomplete AUF in a 74-year-old woman which was surgically treated with prophylactic plate fixation. The patient had been using denosumab for 6 years to treat bone metastases due to thyroid cancer. After surgery, no fractures were observed for 2 years without discontinuing denosumab, and her forearm function was adequate. AUFs are rare and difficult to treat, so oncologists who treat bone metastases need to pay special attention to diagnose this incomplete AUF before the fracture worsens. We believe that detection of a possible fracture and prophylactic surgery can improve prognosis.

Evolution of Surgical Treatment of Metastatic Spine Tumors.

Purpose The treatment of cancer has transformed over the past forty years, with medical oncologists, radiation oncologists and surgeons working together to prolong survival times and minimize treatment related morbidity. With each advancement, the risk-benefit scale has been calibrated to provide an accurate assessment of surgical hazard. The goal of this review is to look back at how the role of surgery has evolved with each new medical advance, and to explore the role of surgeons in the future of cancer care. Methods A literature review was conducted, highlighting the key papers guiding surgical management of spinal metastatic lesions. Conclusion The roles of surgery, medical therapy and radiation have evolved over the past forty years, with new advances requiring complex multidisciplinary care.

The F-18 FDG PET/CT evaluation of the metastatic adrenal lesions of the non-lung cancer tumors compared with pathology results

Background The aim of this study was to evaluate the role of F-18 FDG PET/CT imaging in the diagnosis of primary and metastatic adrenal tumors that originate from non-lung cancer primary tumors. Results F-18 FDG PET/CT images of patients (8 male and 6 female; mean: 55.36 ± 16.2 years old) who attended with the diagnosis of primary or adrenal metastatic lesions other than lung cancer metastasis were evaluated in a retrospective manner. The diameter of the adrenal lesions was mean: 23.93 ± 36.6 mm with SUVmax levels of mean: 9.98 ± 7.8. The primary site of 2/3 of the patients with unknown primary was the adrenal gland, and in one of the patients primary tumor remained unknown during follow-up. Conclusions According to the results of this study, F-18 FDG PET/CT has high diagnostic performance in the diagnosis of the adrenal gland primary and metastatic lesions, which originate from non-lung cancer tumors. Further studies in the larger series are warranted.

Malignancy prediction of cutaneous and subcutaneous neoplasms in canines using B-mode ultrasonography, Doppler, and ARFI elastography

Background Cutaneous and subcutaneous neoplasms are highly prevalent in dogs, ranging from benign to highly aggressive and metastatic lesions. The diagnosis is obtained through histopathology, however it is an invasive technique that may take a long time to obtain the result, delaying the beginning of the adequate treatment. Thus, there is a need for non-invasive tests that can help in the early diagnosis of this type of cancer. The aim of this study was to verify the accuracy of B-mode ultrasonography, Doppler, and ARFI elastography to predict malignancy in cutaneous and subcutaneous canine neoplasms. In addition, we aim to propose an ultrasonography evaluation protocol and perform the neoplasms characterization using these three proposed techniques. Results Twenty-one types of specific neoplasm were diagnosed, and using B-mode, we verified the association between heterogeneous echotexture, invasiveness, presence of hyperechoic spots, and cavity areas with malignancy. An increased pulsatility was verified in malignant neoplasms using Doppler (cut-off value > 0.93). When using the elastography, malignancy was associated with non-deformable tissues and shear wave velocity > 3.52 m/s. Evaluation protocols were proposed associating 4, 5, 6, or 7 malignancy predictive characteristics, and characterization was done for all tumors with at least two cases. Conclusions We concluded that ultrasonography methods are promising and effective in predicting malignancy in these types of tumors, and the association of methods can increase the specificity of the results.

Clinicopathological Features Related to the Efficacy of CDK4/6 Inhibitor-Based Treatments in Metastatic Breast Cancer

Background: Resistance to endocrine therapy has been a major obstacle in the management of hormone receptor (HR)-positive metastatic breast cancer (MBC). Meanwhile, a number of treatments are available to such patients, and physicians often encounter difficulties in choosing the most appropriate treatments for individual patients. The combination of CDK 4/6 inhibitors (CDKi) and endocrine therapy has now become a standard treatment for HR-positive and human epidermal growth factor receptor 2 (HER2)-negative MBC. However, no predictive markers for CDKi-based treatments have been established. Considering their side effects and the financial burden on patients, identifying such markers is crucial. Methods: Clinicopathological features of 107 patients with HR-positive HER2-negative MBC, who received CDKi-based treatments at our institution were retrospectively investigated. HR status in distant metastatic lesions and immunocompetent cells in peripheral blood were also studied. Results: Progression-free survival (PFS) was significantly shorter in patients whose primary tumour was high grade ( P = 0.016) or high neutrophil-to-lymphocyte ratio (NLR) at baseline ( P = 0.017). Meanwhile, there were no differences in other factors, such as expression levels of hormone receptors. Patients whose metastatic lesions were of low tumour grade or high Ki67 labelling index had longer PFS, and such trends were more obvious than primary lesions. Conclusion: Our data indicate that tumour grade in primary lesion and NLR are potential predictive factors for CDKi-based treatments. Moreover, pathological assessment of metastatic lesions might also be useful.

Korean Red Ginseng Enhances Immunotherapeutic Effects of NK Cells via Eosinophils in Metastatic Liver Cancer Model

Metastasis decreases the survival rate of patients with liver cancer. Therefore, novel anti-metastatic strategies are needed. Korean Red Ginseng (KRG) is often ingested as a functional food with an immune-boosting effect. We investigated a combination of KRG and natural killer (NK) cells as a novel immunotherapy approach. SK-Hep1 cells were injected into the tail vein of NRGA mice to establish an experimental metastasis model. KRG, NK cells, or a combination of KRG and NK cells were administered. Tumor growth was observed using an in vivo imaging system, and metastatic lesions were evaluated by histological analysis and immunohistochemistry. Bioluminescence intensity was lower in the KRG and NK cell combination group than in the other groups, indicating that the combination treatment suppressed the progression of metastasis. CD56 expression was used as a NK cell marker and hematological analysis was performed. The combination treatment also decreased the expression of matrix metalloproteinases and the area of metastatic lesions in liver and bone tissues, as well as increased the eosinophil count. Expression of cytokines-related eosinophils and NK cells was determined by Western blotting analysis. The expression of interleukin 33 (IL33) was induced by the combination of KRG and NK cells. High IL33 expression was associated with prolonged overall survival in the Kaplan–Meier plotter. Our results suggest that KRG enhances the immune activity of NK cells by IL-33 through eosinophils and suppresses metastatic liver cancer progression.

Successful Response to Cyclophosphamide, Vincristine, and Dacarbazine Chemotherapy in a Patient with Metastatic Carotid Body Paraganglioma

Carotid body paraganglioma is a rare neuroendocrine tumor presenting with low-grade histological and clinical features. However, the tumor has the potential to produce distant metastasis, and due to its rarity, little information is available regarding chemotherapy for such metastatic lesions. Here, we report a case of carotid body paraganglioma with development of pulmonary and bone metastases 10 years after radical surgery for the primary lesion in the neck. The lesions showed a good response to cyclophosphamide, vincristine, and dacarbazine chemotherapy. A beneficial therapeutic outcome by chemotherapy is extremely rare in patients with metastatic carotid body paraganglioma.

Radiographic assessment of pulmonary metastatic lesions in superficial cutaneous and mammary neoplasms in dogs.

The present study was carried out to assess the pulmonary metastatic lesions in cases of canine superficial and mammary neoplasms presented to the University Veterinary Hospitals, Mannuthy and Kokkalai, Kerala Veterinary and Animal Sciences University during a twelve month period from February 2019 to February 2020. Twenty-four cases of neoplasms in dogs consisting of 12 cases of superficial neoplasms and 12 cases of mammary neoplasms were subjected to fine needle aspiration cytology (FNAC) for the confirmation of malignancy of neoplasm and three view thoracic radiographs were taken to assess the pulmonary metastatic pattern. The results were correlated with the malignancy detected in histopathological analysis after excisional biopsy. The most commonly observed pulmonary metastatic lesions were pulmonary nodules followed by pulmonary micronodules, miliary nodules, and pulmonary mass. These lesions were more evident in malignant mammary neoplasms especially in tubulopapillary carcinoma, ductal carcinoma, and medullary mammary carcinoma with spatial arrangements more in the perihilar region followed by caudodorsal, midventral, and cranioventral area of lung parenchyma. In case of superficial neoplasms miliary patterns and pulmonary microndules were mostly detected as pulmonary metastatic pattern in soft tissue sarcoma, round cell tumour, and malignant fibrohistiocytoma.

[68Ga]Ga-DOTA-FAPI-04 PET/CT in The Staging of Gastric Cancer: Improved Diagnostic Efficacy Confirmed By Postoperative Histopathology

Purpose This study aimed to compare the diagnostic performance of [68Ga]Ga-DOTA-FAPI-04 and [18F]-FDG PET/CT in the primary and metastatic lesions of gastric cancer. Methods Fifty-six patients with histologically proven gastric carcinomas were enrolled in this study. Each patient underwent both [18F]-FDG and [68Ga]Ga-FAPI-04 PET/CT within one week. Activity of tracer accumulation in lesions were assessed by maximum standardized uptake value (SUVmax) and TBR (lesions SUVmax/ ascending aorta SUVmean). Histological work-up including immunohistochemical staining for FAP served as a standard of reference. Results [68Ga]Ga-FAPI PET/CT is superior in detecting primary tumors both in patient-based (100% [45/45] vs. 97.8% [44/45]) and lesion-based analyses (97.8% [45/46] vs. 95.7% [44/46]), showing higher SUVmax (10.25 vs. 8.13, P = 0.004) and TBR (11.63 vs. 5.83, P < 0.001), compared with [18F]-FDG PET/CT. The specificity and positive predictive value of [68Ga]Ga-FAPI were significantly higher than that of [18F]-FDG (100.0% vs. 97.7%, P < 0.001; 100.0% vs. 57.1%, P = 0.001) in determining the lymph node (LN) metastases. [68Ga]Ga-FAPI PET/CT was superior to [18F]-FDG PET/CT in N-staging (47.1% [8/17] vs. 23.5% [4/17]), and in evaluation for LN, peritoneum and bone metastases. [68Ga]Ga-FAPI PET/CT detected positive recurrent lesions in all patients and showed more positive lesions and clearer tumor delineation. Two patients underwent follow-up [68Ga]Ga-FAPI PET/CT scans after chemotherapy, which both showed remission. Conclusions [68Ga]Ga-FAPI PET/CT can better detect primary gastric cancer and metastatic lesions in peritoneum, abdominal LNs and bone, showing high usefulness in guiding N staging. Furthermore, [68Ga]Ga-FAPI PET/CT provides more information for patients with recurrence detection and also has great potential in monitoring response to treatment.