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Background: Soft-tissue metastasis of carcinoma is rare. In the present study, we investigated the surgical indications and clinical features of patients with soft tissue metastases of carcinoma. Methods: In this retrospective cohort study, we enrolled 26 patients with soft tissue carcinoma metastasis referred to our department for treatment. Sex, age, location, size, depth, pain due to the tumor, primary origin, serum C-reactive protein (CRP) level, MRI examinations, diagnosis by a previous physician, carcinoma markers from blood, history of carcinoma, other metastases, performance status (PS), and surgical procedures were documented. Associations between variables and surgery were statistically analyzed. Results: The primary cancer origin was found to be the lung (n = 10), kidney (n = 7), esophagus (n = 2), stomach (n = 1), breast (n = 1), liver (n = 1), ureter (n = 1), anus (n = 1), and unknown (n = 2). The mean CRP level of all patients was 2.3 mg/dL. Seven tumors (26.9%) were originally suspected to be soft tissue metastases of carcinoma, while 19 tumors (73.1%) were considered soft tissue sarcomas or inflammatory lesions by the previous treating physician. Twenty patients (76.9%) had other metastases. The PS of the 12 patients (46.2%) was zero. Eleven patients (42.3%) underwent surgery for soft tissue metastases. Diagnosis of soft tissue metastasis by a previous physician and good PS (p < 0.05) were significantly associated with surgery. Conclusion: Overall, the present results show that surgical indications for soft tissue metastasis of carcinoma include diagnosis by the referring physician or good PS of the patients. [ABSTRACT FROM AUTHOR]

In the present study, a patient-derived orthotopic xenograft (PDOX) model of recurrent cisplatinum (CDDP)-resistant metastatic osteosarcoma was treated with Salmonella typhimurium A1-R (S. typhimurium A1-R), which decoys chemoresistant quiescent cancer cells to cycle, and recombinant methioninase (rMETase), which selectively traps cancer cells in late S/G2, and chemotherapy. The PDOX models were randomized into the following groups 14 days after implantation: G1, control without treatment; G2, CDDP (6 mg/kg, intraperitoneal (i.p.) injection, weekly, for 2 weeks); G3, rMETase (100 unit/mouse, i.p., daily, for 2 weeks). G4, S. typhimurium A1-R (5 × 107 CFU/100 μl, i.v., weekly, for 2 weeks); G5, S. typhimurium A1-R (5 × 107 CFU/100 μl, i.v., weekly, for 2 weeks) combined with rMETase (100 unit/mouse, i.p., daily, for 2 weeks); G6, S. typhimurium A1-R (5 × 107 CFU/100 μl, i.v., weekly, for 2 weeks) combined with rMETase (100 unit/mouse, i.p., daily, for 2 weeks) and CDDP (6 mg/kg, i.p. injection, weekly, for 2 weeks). On day 14 after initiation, all treatments except CDDP alone, significantly inhibited tumor growth compared to untreated control: (CDDP: p = 0.586; rMETase: p = 0.002; S. typhimurium A1-R: p = 0.002; S. typhimurium A1-R combined with rMETase: p = 0.0004; rMETase combined with both S. typhimurium A1-R and CDDP: p = 0.0001). The decoy, trap and kill combination of S. typhimurium A1-R, rMETase and CDDP was the most effective of all therapies and was able to eradicate the metastatic osteosarcoma PDOX.

The in vitro efficacy of the disintegrin echistatin was tested on a high-metastatic variant of 143B human osteosarcoma, 143B-LM4, which over-expresses αvβ3 integrin. Echistatin is an RGD cyclic peptide and an antagonist of αvβ3 integrin. In the present study, echistatin inhibited cell proliferation, migration, invasion, and adhesion of 143B-LM4 cells. 143B-LM4 cell proliferation decreased after treatment with echistatin in a time-dependent and dose-dependent manner (P

The in vitro efficacy of the disintegrin echistatin was tested on a high-metastatic variant of 143B human osteosarcoma, 143B-LM4, which over-expresses αvβ3 integrin. Echistatin is an RGD cyclic peptide and an antagonist of αvβ3 integrin. In the present study, echistatin inhibited cell proliferation, migration, invasion, and adhesion of 143B-LM4 cells. 143B-LM4 cell proliferation decreased after treatment with echistatin in a time-dependent and dose-dependent manner (P

Backgrounds: Immune checkpoint inhibitors (ICIs) can significantly prolong the survival of patients with advanced non‐small‐cell lung cancer (NSCLC); however, few studies on the therapeutic effects of ICIs on bone metastases were performed. Methods: This retrospective study aimed to investigate the therapeutic effects of ICIs and determine predictors of favorable ICI response and prognosis in 55 advanced NSCLC patients with bone metastases who initiated ICI treatment between 2016 and 2019, with a mean follow‐up period of 23.2 months. Patients were classified into responders (complete or partial response) and non‐responders (stable or progressive disease) according to the MD Anderson Cancer Center (MDA) criteria, and the predictors of therapeutic response were identified using multivariate logistic regression analysis. Furthermore, overall survival from the time of ICI administration to the final follow‐up or death was evaluated, and prognostic predictors were identified using Cox proportional hazards regression analysis. Results: ICI response rate was 30.9% (complete in three cases, partial in 14). Median survival time was 9.3 months, with 1‐year and 2‐year survival rates of 40.6% and 19.3%, respectively. Responders survived significantly longer than non‐responders (p = 0.03). Based on the receiver operating characteristic curve, the predictive cutoff value of the pretreatment neutrophil‐to‐lymphocyte ratio (NLR) was 2.1. Multivariate analysis identified female sex (p = 0.03), use of ICIs as first‐line therapy (p < 0.01), and NLR <2.1 (p = 0.03) as significant predictors of therapeutic response, whereas concomitant use of a bone‐modifying agent (p < 0.01), Katagiri score ≤6 points (p < 0.01), and NLR <2.1 (p = 0.02) were identified as significant predictors of good prognosis. Conclusions: This study identified some novel predictors for favorable therapeutic response and prognosis in advanced NSCLC patients with bone metastases undergoing ICI treatment. Pretreatment NLR less than 2.1 can be considered the most important predictor. [ABSTRACT FROM AUTHOR]

Background. We report a retrospective case series analysis of clinical outcomes of patients with soft tissue sarcoma around the elbow. Methods. Twenty-two patients underwent surgical tumor excision between January 1999 and May 2017, with a mean follow-up of 85.2 months. Results. Six tumors were localized in the upper arm, nine in the elbow, and seven in the forearm. Sixteen tumors were deep-seated, and six were superficially located. Fifteen patients underwent wide excision, including one amputation, and 18 achieved (81.8%) negative margins histologically. Two local recurrences and four distant metastases developed. The mean Musculoskeletal Tumor Society score was 92.0% (range, 33.3–100). The 5-year local recurrence-free survival rate, metastasis-free survival rate, and overall survival rate were 90.0%, 77.0%, and 79.7%, respectively. Conclusions. Local control and limb function can have favorable outcomes when the tumor excised has a histologically negative margin without sacrificing the major structure. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Simple Summary: With the prolonged survival of metastatic cancer patients, medium to long-term outcomes of local therapy for oligometastases are important and should be discussed. Metastasectomy is a reasonable treatment for isolated lesions when feasible. This retrospective study aimed to examine the medium to long-term outcomes of spinal metastasectomy in 124 patients with isolated spinal metastases who underwent metastasectomy. The primary malignancy was renal cell carcinoma in 51 patients, thyroid carcinoma in 14 patients, low-grade sarcoma in 13 patients, lung cancer in 13 patients, breast cancer in 12 patients, and other malignancies in 21 patients. The 3-year and 5-year survival rates were 70% and 60%, respectively. Patients with thyroid cancer had the best survival results. The occurrence rates for the local recurrence of the operated spinal lesion and instrumentation failure were 10% and 22%, respectively. For certain patients with isolated and removable spine metastases, metastasectomy can be a useful treatment option. The prolonged survival of metastatic cancer patients highlights the importance of the local control of spinal metastases, which reduce patient performance status. This retrospective study examined the medium to long-term outcomes of spinal metastasectomy by evaluating 124 patients who underwent metastasectomy for isolated spinal metastases (2006–2018) with a postoperative follow-up for a minimum of 3 years. The findings present information on patient demographics (i.e., performance status, location of non-spinal metastases, and history of systemic therapy) and postoperative outcomes, including perioperative complications, disease progression of non-operated metastases, and additional excisional surgeries. Additionally, postoperative survival, local tumor control in the operated spine, and maintenance of spinal reconstruction without instrumentation failure were determined using Kaplan–Meier analyses. The primary malignancy was kidney and thyroid cancer in 51 and 14 patients, respectively, low-grade sarcoma and lung cancer in 13 patients, breast cancer in 12 patients, and other malignancies in 21 patients. The 3-year and 5-year survival rates were 70% and 60%, respectively. We found that patients with thyroid cancer had the best survival results, with local tumor recurrence and instrumentation failure at 10% and 22%, respectively. These findings suggest that for certain patients with isolated and removable spine metastases, metastasectomy can improve function and survival. [ABSTRACT FROM AUTHOR]

Background: The use of surgical metastasectomy (SM) has increased across cancer types in recent decades despite the increasing efficacy of modern systemic treatment modalities. Symptomatic spinal metastases severely compromise patients' performance status. However, as spinal SM is a complex surgery with potentially significant complications, it is not considered the treatment of choice. Methods: We reviewed the articles on SM in several primary cancers with different types of metastatic lesions and extracted the data from relevant articles to provide a comprehensive review including the surgical techniques, indications, reported outcomes, and future prospects of SM in spinal metastases. Results: Total en bloc spondylectomy (TES) is a method of spinal SM associated with a lower risk of tumor recurrence and complications. Intralesional transpedicular osteotomy using a fine threadwire saw allows prevention of spinal cord and nerve root injuries. Spinal SM is considered suitable for patients with controlled primary disease having no evidence of disseminated extraspinal metastases, a completely resectable solitary lesion in the spine, and adequate cardiopulmonary reserve to tolerate the surgery. Metastatic lesions from kidney and thyroid cancers have been reported as the best candidates for spinal SM. Although data about spinal SM are limited, the reported outcomes are favorable with acceptable local recurrence rates in long‐term follow‐up. Conclusion: In patients with isolated resectable spinal metastases, complete SM including TES is a useful option as it can improve function and survival. However, appropriate patient selection and surgical feasibility remain the most important aspects of management. Implications for Practice: Surgical metastasectomy for spinal metastases may be a potentially curative treatment option with a low risk of local recurrence and lead to prolonged long‐term survival if appropriate patients are selected and if the surgery is carried out by experienced surgeons in high‐volume centers. This review focuses on surgical techniques for complete surgical metastasectomy of spinal metastatic lesions, the potential indications, and the published clinical outcomes, and discusses the future prospects. [ABSTRACT FROM AUTHOR]

Osteosarcoma is the most frequent type of primary bone tumor in children and adolescents, thus care for patients with malignant osteosarcoma is strongly required. The roles of small extracellular vesicles (SEVs) in enhancing metastases have been demonstrated in multiple tumors, but they are still poorly understood in osteosarcoma. Hence, this study investigated the effects of SEVs on progression and the tumor microenvironment in mice and patients. In an orthotopic implantation study, we found that osteosarcoma-derived SEVs had the potential to enhance metastases and angiogenesis. In addition, osteosarcoma-derived SEVs decreased the number of mature osteoclasts in vivo. In vitro osteoclastogenesis studies revealed that the inhibition of osteoclast maturation by osteosarcoma-derived SEVs was mediated by suppressing the NF-κB signal pathway. MicroRNA analysis of SEVs from different malignant human osteosarcomas revealed that miR-146a-5p was involved in the inhibition of osteoclastogenesis. In osteosarcoma patients, lower numbers of osteoclasts in biopsy specimens at the first visits were correlated with higher malignancy. These findings indicated that osteosarcoma-derived SEVs enhance distant metastasis of osteosarcomas by inhibiting osteoclast maturation, which may be a useful prognostic marker. This diagnostic method may enable to predict malignancy at early stage, and help to provide optimal care to patients with risk of high malignancy. [ABSTRACT FROM AUTHOR]

Purpose: Leiomyosarcoma (LMS) is generally resistant to radiation and chemotherapy. Our study aimed to examine the outcomes of total en bloc spondylectomy (TES) for spinal metastatic LMS and to analyze potential factors associated with survival. Methods: This study included 10 consecutive patients who underwent TES for spinal metastatic LMS at our institute between 2005 and 2016 and were followed up at a minimum of 3 years after surgery. At the time of TES, all the 10 patients had solitary bone metastases in the spine. Seven patients had a lowered performance status (PS) with an eastern cooperative oncology group (ECOG) grade of 2 or 3 due to back pain or neurological symptoms. The cancer-specific survival (CSS) time from TES to death or last follow-up was the main endpoint. Potential factors associated with survival were evaluated using the Kaplan–Meier analysis and the log-rank test. Results: Five patients underwent a single vertebral resection, and the other five patients underwent two or three consecutive vertebral resections. Three patients developed perioperative complications including pulmonary thromboembolism and pneumothorax. Nine patients improved or fairly maintained their PS with an ECOG grade of 1. The 1-, 3-, and 5-year CSS rates after TES were 90%, 70%, and 47%, respectively. Only postoperative disability (ECOG PS grade 3) was significantly associated with short-term survival after TES. Conclusions: The clinical outcomes of 10 patients who underwent TES for spinal metastatic LMS were favorable without severe complications. Postoperative disability was significantly associated with short-term survival after TES. [ABSTRACT FROM AUTHOR]

Spinal metastases ( SMs) from thyroid cancers significantly reduce the quality of life by causing pain and neurological deficits and increase mortality. Complete surgical resection of isolated thyroid SMs is a promising treatment option; however, the postoperative outcome is unknown. This study aimed to compare the postoperative courses of patients undergoing complete resection of thyroid SMs with those of patients undergoing incomplete resection, with a minimum 4-year follow-up. We performed a retrospective analysis of 32 patients who underwent tumor excision surgery for thyroid SMs at our medical center during a 28-year period. Twenty patients underwent complete excision, and 12 underwent incomplete excision. Survival was defined as the time from the first spinal surgery to death or last follow-up. Kaplan-Meier analysis with the long-rank test was used to compare the overall survival rates between the groups. For all patients, the overall 5- and 10-year survival rates were 71% and 31%, respectively. The median overall survival time was 6.4 years. The patients undergoing complete excision survived longer than those undergoing incomplete excision (5-year survival: 84% vs. 50%; 10-year survival: 52% vs. 8%; P < 0.01). Only one patient undergoing complete excision experienced local tumor recurrence in the operated spine, whereas all long-term survivors (>18 months after surgery) in the incomplete excision group experienced local tumor recurrence and a consequent deterioration in performance status. Complete surgical resection of thyroid SMs, if achievable, has the potential not only to maintain performance status, but also to prolong survival. [ABSTRACT FROM AUTHOR]

Background: A tenosynovial giant cell tumor (T-GCT) is a benign synovial tumor arising from the synovium, bursae, or tendon sheath. It can be intra- or extra-articular and localized or diffuse. Diffuse T-GCT is considered as a locally aggressive. Positron emission tomography (PET) with fluorine-18 fluorodeoxyglucose with computed tomography (FDG PET/CT) is widely used to differentiate malignant from benign tumors and to detect distant metastasis. However, FDG PET/CT is limited by false-positive findings. In this study, we present two cases of T-GCT that developed in unusual locations and were confused with malignant tumors. The final diagnoses were histologically confirmed as T-GCTs.Case Presentation: Case 1. A 45-year-old Japanese female presented with a left choroidal melanoma and an abnormal lesion adjacent to the first cervical (C1) lamina confirmed by a PET scan (maximum standardized uptake value [SUVmax] =9.9 g/ml). MRI of the neck also detected a soft tissue mass (14.6 × 7.7 × 7 mm) adjacent to the C1 lamina. The choroidal melanoma was treated by heavy carbon ion radiotherapy. Although the size of the C1 soft tissue tumor remained unchanged, a CT-guided biopsy confirmed the diagnosis of the neck mass as a T-GCT. Case 2. A 15-year-old Japanese male with multiple type 1 neurofibromatosis presented with a soft tissue mass (26.1 × 24.7 × 11.5 mm) of the extra-articular hip joint that was coincidentally detected by FDG PET/CT during examination of a mediastinal soft tissue mass. SUVmax of the mediastinal lesion was 2.6 g/ml and of the hip lesion was 12.8 g/ml. Thus, differentiation from a malignant tumor, such as a malignant peripheral nerve sheath tumor, was necessary. An open biopsy was performed, and the frozen section was diagnosed as T-GCT. The tumor was excised, and the final histological diagnosis confirmed T-GCT.Conclusion: T-GCT can show high FDG uptake, which might be confused with malignancy. Although MRI findings and location might help in the diagnosis of a T-GCT, careful assessment is mandatory, especially in unusual locations. [ABSTRACT FROM AUTHOR]

Purpose: Total en bloc spondylectomy (TES) is accompanied by preoperative embolization of segmental arteries, which is limited to three consecutive levels to avoid the risk of spinal cord ischemia. We retrospectively examined the efficacy and safety of repeated TES with embolization of more than three levels of segmental arteries.Methods: Seven patients underwent TES twice for spinal metastases at different levels. Every patient underwent embolization of the bilateral segmental arteries before each surgery. We assessed the total number of segmental arteries embolized, the existence of Adamkiewicz arteries during the embolization procedure, intraoperative blood loss, and the motor function of the lower limbs, using the American Spinal Injury Association (ASIA) motor score.Results: No patient experienced any motor deficit after embolization. During the embolization procedure, an Adamkiewicz artery was depicted in five patients, which precluded embolization at that level. The median number of segmental arteries embolized in total was 9 (9-11). Intraoperative blood loss (median, IQR) was 480 (420-630) ml during the first surgery and 520 (280-600) ml during the second surgery. The ASIA motor scores (median, IQR) were as follows; 100 (98-100) (first admission), 100 (100-100) (first discharge), 100 (98-100) (second admission), and 97 (94-100) (second discharge). No patients had developed statistically significant neurological deterioration, and there had been no local recurrence after a median follow-up of 17.8 months (range 1-51 months).Conclusion: Repeated TES procedures can be performed safely even if more than three levels of segmental arteries are embolized. [ABSTRACT FROM AUTHOR]

Background: Total en bloc spondylectomy (TES) is associated with a high complication rate because it is technically demanding and involves patients compromised by cancer. Specifically, perioperative complications are more likely to occur in patients receiving preoperative irradiation. We examined the perioperative complications associated with TES in patients receiving preoperative irradiation. Methods: Seventy-seven patients underwent TES between May 2010 and April 2013. We performed a retrospective review of prospectively collected data for 50 patients with metastatic tumors of the thoracic spine, excluding patients with primary spinal tumors, lumbar spinal metastasis, and combined anterior and posterior approach TES. Patients were divided into 2 groups: those with preoperative irradiation (RT-TES group, 18 patients) and those without preoperative irradiation (TES group, 32 patients). The following perioperative complications, occurring within 2 months of surgery, were compared between the groups: intraoperative dural injuries, epidural hematomas, deep surgical-site infections, postoperative cerebrospinal fluid leakage, wound dehiscence, pleural effusions, and neurological deficits. Results: Significant differences in patient characteristics were not observed between the RT-TES and TES groups. Perioperative TES complications occurred in 20/50 patients (40.0%). The complication rate in the RT-TES group was 77.8% (14 out of 18), threefold higher than the 18.8% (6 out of 32) in the TES group (P<0.01). The incidence of complications, including intraoperative dural injuries, postoperative cerebrospinal fluid leakage, wound dehiscence, and pleural effusions, was significantly higher in the RT-TES group (P<0.01). Conclusion: The perioperative complication rate associated with TES for spinal metastasis was significantly higher among patients receiving preoperative irradiation than among those not receiving preoperative irradiation. [ABSTRACT FROM AUTHOR]

Purpose: Distant metastases from thyroid carcinoma are successfully cured if they take up radioiodine (I), are of small size, and located in the lungs. Bone metastases have the worst prognosis because I therapy and external beam radiotherapy are less effective. Our propose here is to report a patient with solitary spinal metastasis and multiple lung metastases from thyroid carcinoma, whose spinal metastasis was treated by total en bloc spondylectomy (TES) enhancing antitumor immunity using frozen tumor-bearing bone for spinal reconstruction. Methods: The patient was a 37-year-old male who had solitary spinal metastasis at T4 and multiple lung metastases from thyroid carcinoma. I therapy for the multiple lung metastases resulted in no effect because the apparent I uptake was observed only in T4 metastasis. We performed a TES of T4 with cryotreatment. After en bloc excision of T4, the excised tumor-bearing vertebra was frozen by liquid nitrogen. In spinal reconstruction, the frozen vertebra was used in a mesh cage inserted into the anterior defect. Results: After surgery, the thyroglobulin level decreased without any other adjuvant therapy and the serum levels of INF-γ and IL-12 increased. This indicates antitumor immunity was activated. Then, I therapy became effective to the lung metastases causing the tumors to decrease in size and number. Three years after surgery, progression in the lung metastases, other metastasis, and local recurrence have not been observed. Conclusions: TES with cryotreatment as presented is a novel surgery which can enhance antitumor immunity against other visible or non-visible metastases. [ABSTRACT FROM AUTHOR]

Background: We investigated whether molecular prognostic factors should be evaluated in specimens of the primary or the metastatic lesion and if the prognosis after initial pulmonary metastasectomy can be predicted based on evaluation of metastatic lesion specimens in osteosarcoma patients. Methods: This retrospective study included 29 osteosarcoma patients with pulmonary metastases (19 males, 10 females; age 21 ± 10 years). Molecular prognostic factors were the levels of vascular endothelial growth factor type A (VEGF-A), VEGF type C (VEGF-C), and Ki67. Primary and pulmonary metastatic lesions could be compared in 18 patients regarding the values of marker expressions and the prognosis after initial pulmonary resection. Finally, the prognosis of all 29 cases was compared according to the molecular markers of the metastatic lesions. Results: Evaluation of the metastatic lesions reflected the prognosis after pulmonary metastasectomy more than that of the primary lesions. In the metastatic lesions, positive expression of VEGF-A ( n = 15), VEGF-C ( n = 2), and Ki67 ( n = 15) was associated with a significantly poorer prognosis ( p = 0.0013, 0.0001, and 0.037, respectively). No patients with positive expression of both VEGF-A and Ki67 ( n = 7) survived more than 5 years after the initial pulmonary resection. All patients who had negative reactions to both VEGF-A and Ki67 ( n = 6) were alive at the end of the study. Conclusions: Molecular prognostic factors should be investigated in specimens of the metastatic lesion. Combined evaluation of VEGF-A and Ki67 and of VEGF-C using pulmonary metastatic lesion specimens in osteosarcoma patients effectively reflects survival after pulmonary metastasectomy. [ABSTRACT FROM AUTHOR]

This letter to the editor responds to comments on a recently published review article on metastasectomy in the spine. [ABSTRACT FROM AUTHOR]

Background: Total en bloc spondylectomy (TES) is a surgery designed to achieve complete resection of a malignant spinal tumor such as spinal metastasis. Although this procedure decreases the rate of local recurrence, it is questionable whether local control prolongs patient’s survival. We developed a “second-generation TES” that brings about TES enhancing antitumor immunity to prolong patient’s survival. Our purpose is to present a second-generation TES applied tumor-induced cryoimmunology and assess the immunity-enhancing effect after implementing this surgery. Methods: We performed a retrospective review of prospectively collected data in second-generation TES as carried out in 56 cases. In second-generation TES, instead of harvesting autograft from the ilium or fibula, the resected lamina and vertebral body from TES are frozen using liquid nitrogen and used as grafted bone for spinal reconstruction. In recent 26 of the 56 cases, in addition to the TES procedure, a small amount of the tumor tissue from the resected tumor-bearing vertebra was also placed into liquid nitrogen. This small amount of tumor tissue was then implanted subcutaneously on one side of the axilla. In 52 of 56 cases, measurement of interleukin 12 (IL-12) was performed before surgery and at both 1 and 3 months after surgery. Results: IL-12 increased after TES surgery in 38 of 52 cases (73.1%). The mean IL-12 relative concentrations at both 1 and 3 months after surgery, as compared to before surgery, were significantly higher (121±89 and 149±111%: P<0.05 and P<0.01). Conclusions: Our results show that second-generation TES may provide not only a local radical cure but also a systemic immunological enhancement. Further prolonged survival in patients with a malignant spinal tumor is promising by second-generation TES. [ABSTRACT FROM AUTHOR]

Imaging with fluorescent proteins has been revolutionary and has led to the new field of in vivo cell biology. Many new applications of this technology have been developed. Green fluorescent protein (GFP)-labeled or red fluorescent protein (RFP)-labeled HT-1080 human fibrosarcoma cells were used to determine clonality of metastasis by imaging of metastatic colonies after mixed implantation of the red and green fluorescent cells. Resulting pure red or pure green colonies were scored as clonal, whereas mixed yellow colonies were scored as nonclonal. Dual-color fluorescent cancer cells expressing GFP in the nucleus and RFP in the cytoplasm were engineered. The dual-color cancer cells enable real-time nuclear-cytoplasmic dynamics to be visualized in living cells in vivo, including mitosis and apoptosis. The nuclear and cytoplasmic behavior of dual-color cancer cells in real time in blood vessels was observed as they trafficked by various means or extravasated in an abdominal skin flap. Dual-color cancer cells were also visualized trafficking through lymphatic vessels where they were imaged via a skin flap. Seeding and arresting of single dual-color cancer cells in the lung, accumulation of cancer-cell emboli, cancer-cell viability, and metastatic colony formation were imaged in real time in an open-chest nude mouse model using assisted ventilation. Novel treatment was evaluated in these imageable models. UVC irradiation killed approximately 70% of the dual-color cancer cells in a nude mouse model. An RFP-expressing glioma was transplanted to the spinal cord of transgenic nude mice expressing nestin-driven green fluorescent protein (ND-GFP). In ND-GFP mice, GFP is expressed in nascent blood vessels and neural stem cells. ND-GFP cells staining positively for neuronal class III-β-tubulin or CD31 surrounded the tumor, suggesting that the tumor stimulated both neurogenesis and angiogenesis. The tumor caused paralysis and also metastasized to the brain. The Salmonella typhimurium A1-R tumor-targeting bacterial strain was administered in the orthotopic spinal cord glioma model. The treated animals had a significant increase in survival and decrease in paralysis. S. typhimurium A1-R was effective against primary bone tumor and lung metastasis expressing RFP in a nude mouse model. S. typhimurium A1-R was effective against both axillary lymph and popliteal lymph node metastases of human dual-color pancreatic cancer and fibrosarcoma cells, respectively, as well as lung metastasis of the fibrosarcoma in nude mice. Imaging with fluorescent proteins will reveal mechanisms of cancer progression and provide visual targets for novel therapeutics. [ABSTRACT FROM AUTHOR]

Simple Summary: Patients with bone metastases (BMs) from differentiated thyroid carcinoma (DTC) can live longer than those with BMs from other cancers. BMs from DTC create destructive lesions and easily cause intractable pain and neurological symptoms, including paralysis. These symptoms related to BMs affect mortality directly and indirectly by hampering the application of systemic therapies. Therefore, long-term local control of BMs in patients with DTC is desired, especially in patients with single or a small number of metastases. Local treatments for BMs have recently become advanced and sophisticated in surgery, radiotherapy, and percutaneous procedures. These therapies, either alone or in combination with other treatments, can effectively improve, or prevent the deterioration of, the performance status and quality of life of patients with DTC-BM. Among local therapies, complete surgical resection and stereotactic radiosurgery are the mainstay for achieving long-term control of DTC-BM. After the lung, the skeleton is the second most common site of distant metastases in differentiated thyroid carcinoma (DTC). Patients with osteolytic bone metastases (BMs) from thyroid carcinoma often have significantly reduced performance status and quality of life. Recent advancements in cancer therapy have improved overall survival in multiple cancer subtypes, including thyroid cancer. Therefore, long-term local control of thyroid BMs is desired, especially in patients with a single metastasis or oligometastases. Here, we reviewed the current management options for DTC-BMs and especially focused on local treatments for long-term local tumor control from an orthopedic tumor surgeon's point of view. Metastasectomy and stereotactic radiosurgery can be performed either alone or in combination with radioiodine therapy and kinase inhibitors to cure skeletal lesions in selected patients. Percutaneous procedures have been developed in recent years, and they can also have a curative role in small BMs. Recent advancements in local therapies have the potential to provide not only long-term local tumor control but also a better prognosis. [ABSTRACT FROM AUTHOR]

The article focuses on a study that quantified the receptor for advanced glycation endproducts (RAGE) and its ligand, high-mobility group box-1 (HMGB1), in enchondromas and chondrosarcomas to determine whether these markers were associated with histological malignancy and prognosis. The results indicate that high expression of endogenous secretory RAGE in grade 1 chondrosarcoma was associated with subsequent recurrence, lung metastasis and poor survival.

It is well known that the coagulation factor XIII (FXIII) is deeply involved in wound healing and tissue regeneration. We measured the plasma levels of FXIII (FXIII levels) before and after surgery in 80 patients with bone tumors [benign tumors in 30 patients (BT group), malignant tumors in 30 patients (MT group), and carcinoma metastasis in 20 patients (CM group)] and in the control group which consisted of 30 patients with osteoarthritis of the hip joint who had underwent total hip arthroplasty (THA). The numbers of patients whose preoperative FXIII level was below the lower limit of normal were as follows: 0 (0%) among 30 patients in the control group; 7 (23%) among 30 patients in the BT group; 12 (40%) among 30 patients in the MT group; and 9 (45%) among 20 patients in the CM group. Among patients with bone tumors examined in this study, patients with osteosarcoma who underwent chemotherapy showed a significant decrease in FXIII levels (p < 0.01). We indicated not only FXIII levels in patients with bone tumors, but also the natural time-course of FXIII levels in patients who underwent orthpaedic surgery of THA at the first time. [ABSTRACT FROM AUTHOR]

Rhabdomyosarcoma, the most common soft tissue sarcoma noted in childhood, requires multimodality treatment, including chemotherapy, surgical resection, and/or radiation therapy. The majority of the patients with localized rhabdomyosarcoma can be cured; however, the long-term outcomes in patients with metastatic rhabdomyosarcoma remain poor. The standard chemotherapy regimen for patients with rhabdomyosarcoma is the combination of vincristine, actinomycin, and cyclophosphamide/ifosfamide. In recent clinical trials, modifications of the standard chemotherapy protocol have shown improvements in the outcomes in patients with rhabdomyosarcoma. In various type of malignancies, new treatments, such as molecular targeted drugs and immunotherapies, have shown superior clinical outcomes compared to those of standard treatments. Therefore, it is necessary to assess the benefits of these treatments in patients with rhabdomyosarcoma. Moreover, recent basic and clinical studies on rhabdomyosarcoma have reported promising therapeutic targets and novel therapeutic approaches. This article reviews the recent challenges and advances in the management of rhabdomyosarcoma. [ABSTRACT FROM AUTHOR]

Background: Limited evidence is available regarding the dissemination of tumor tissues due to compression during massage therapy, a routine procedure in patients with various symptoms in Asian countries.Case Presentation: A 12-year-old male presented at a massage clinic with pain and swelling of his left knee, which worsened the same night. Consistent with conventional osteosarcoma, radiography revealed cortical bone destruction, osteoblastic changes, and periosteal reactions. Magnetic resonance imaging revealed a tumor in the distal femur, an extraskeletal mass, and an infiltrative lesion in the intramuscular and neurovascular areas surrounding the distal femur; this was considered as hemorrhage and dissemination of the tumor tissue. 18Fluorine-labelled fluorodeoxyglucose-positron emission tomography and computed tomography revealed multiple metastases in the spine, liver, and lung. Consistent with osteosarcoma, histopathological examination revealed tumor cell proliferation with extensive pleomorphism and mitoses. Despite undergoing chemotherapy, radiation therapy, and hip disarticulation, the patient died due to multiple metastases 13 months after the initial diagnosis.Conclusions: The present case suggests association of massage therapy with the local dissemination of tumor tissues, although influence of massage therapy on metastatic lesions remains unclear. Massage therapists should be aware of the possibility for dissemination of hidden malignancies due to the procedure. [ABSTRACT FROM AUTHOR]

Due to the rarity and heterogeneity of bone and soft-tissue sarcomas, investigation into molecular targets and new treatments has been particularly challenging. Although intensive chemotherapy and establishment of surgical procedures have improved the outcomes of patients with sarcoma, the curative rate of recurrent and metastatic sarcomas is still not satisfactory. Recent basic science research has revealed some of the mechanisms of progression and metastasis of malignancies including proliferation, apoptosis, angiogenesis, tumor microenvironment, migration, invasion, and regulation of antitumor immune systems. Based on these basic studies, new anticancer drugs, including pazopanib, trabectedin, eribulin, and immune checkpoint inhibitors have been developed and the efficacies and safety of the new drugs have been assessed by clinical trials. This review summarizes new molecular therapeutic targets and advances in the treatment for bone and soft tissue sarcomas. [ABSTRACT FROM AUTHOR]

Background: Spinal metastases of gastrointestinal stromal tumors are rare; however, the incidence has been increasing since the introduction of tyrosine kinase inhibitors, which have improved overall survival. Due to the rarity of cases, there are no treatment guidelines for spinal metastases of gastrointestinal stromal tumors. We describe a patient who underwent spinal metastasectomy for a rectal gastrointestinal stromal tumor; we further provide a review of all cases of gastrointestinal stromal tumors with spinal metastases.Case Presentation: A 51-year-old Japanese man who had undergone resection for a rectal gastrointestinal stromal tumor was diagnosed with L3 vertebral metastasis 10 years after surgery. As there were no metastases to vital organs, an en bloc corpectomy of the L3 vertebral body, using bilateral retroperitoneal approaches, was performed to achieve local cure and to prevent neural compression. A 3-year follow-up showed no local recurrence or new metastases; he had full neurological function.Conclusions: Spinal metastasectomy can be an effective treatment for solitary spinal metastases of gastrointestinal stromal tumors. [ABSTRACT FROM AUTHOR]

The purpose of this study was to evaluate perioperative complications and prognosis associated with curative surgical resection, such as total en bloc spondylectomy, for spinal metastases in elderly patients. We retrospectively reviewed 103 consecutive patients who underwent curative surgery between 2010 and 2017 and divided them into group 1 (n = 27, age <50 years), group 2 (n = 47, age ≥50 and <65 years), and group 3 (n = 29, age ≥65 years). Perioperative complication rate and overall survival (OS) after surgery was evaluated. A total of 129 perioperative complications were observed in 76 of 112 surgeries. Among the 3 groups, the total number of complications per person was the highest in group 3, although the difference was not statistically significant. The total number of serious complications per person was the highest in group 3, which was statistically significant. (0.23 vs. 0.51 vs. 0.90; P < 0.05). No significant difference in OS was observed between the groups. In group 3, a significant difference in OS was found between subgroups 1 (renal cell, thyroid, and breast cancer metastasis) and 2 (other primary tumors) (P < 0.01). In group 3, 24 patients (83%) either maintained or had regained their ambulatory capacity at the final follow-up. Elderly patients who underwent curative surgery had significantly more frequent serious postoperative complications than nonelderly patients. Even in patients with advanced age, curative surgical resection can provide favorable prognosis and local control, especially in those with spinal metastases of renal cell and thyroid cancer. [ABSTRACT FROM AUTHOR]

Background Spinal metastases (SMs) from kidney and thyroid cancers have several common features suggesting that excisional surgery for isolated and removable SMs can improve survival. We propose a simple treatment algorithm for SMs from these cancers. Our study aimed to evaluate the efficacy of the algorithm. Methods We performed a retrospective analysis of the data of 69 consecutive patients (48 with kidney and 21 with thyroid cancers) who underwent excisional surgery for SMs between 1995 and 2014. The patients were retrospectively classified into an indicated group for excisional SM surgery and a nonindicated group according to our algorithm, and the Tokuhashi and Tomita scoring systems. Patients in the indicated group were expected to survive ≥2 years postoperatively, whereas those in the nonindicated group were not. The positive predictive value and negative predictive value (NPV) were calculated using the predicted versus actual survival times of the patients. Survival was defined as the time from the first excisional surgery for the spinal lesion to death or the last follow-up of ≥2 years. Results For patients with kidney cancer, the 2- and 5-year survival rates were 85.4% and 60.4%, respectively. For patients with thyroid cancer, the 2- and 5-year survival rates were 100% and 83.8%, respectively. Our algorithm had a compatible high positive predictive value (95.5%) and NPV (100%), whereas the Tokuhashi and Tomita scoring systems had low NPVs of 15.8% and 13.3%, respectively. Conclusions Our treatment algorithm of SMs from kidney and thyroid cancers is useful for determining an adequate treatment including excisional surgery. [ABSTRACT FROM AUTHOR]