Optimal Prognostic Factors for Metastatic and Inoperable Sarcomas Treated With Pazopanib, Eribulin, and Trabectedin.

BACKGROUND/AIM: The prognosis of metastatic and inoperable sarcomas is extremely poor, and intensive chemotherapy-based treatment is typically administered to prolong survival. Currently, pazopanib, eribulin, and trabectedin are key drugs used in patients with these sarcomas. The aim of the study was to identify prognostic factors for metastatic and inoperable bone and soft tissue sarcomas. PATIENTS AND METHODS: Clinicopathological data of 46 patients with metastatic and inoperable sarcomas treated with pazopanib, eribulin, and trabectedin between January 2013 and February 2022 at our institution were retrospectively analyzed. Age, sex, primary tumor location, adverse effects, history of doxorubicin and radiation therapy, performance status scores, maximum tumor response, and survival duration were evaluated. The significant prognostic factors were identified using Cox proportional hazards models. Moreover, the 5-year survival rate was evaluated using the Kaplan-Meier method. RESULTS: The median survival duration after treatment was 13.3 months, where the 5-year overall survival rate was estimated to be 9.85%. Both univariate and multivariate analyses revealed significant relationships among patient prognosis, performance status, and tumor response. CONCLUSION: Performance status scores and tumor response were significantly associated with patient prognosis. Therefore, regardless of age, sex, primary tumor location, adverse effects, and history of doxorubicin and radiation therapy, use of cutting-edge drugs, such as pazopanib, eribulin, and trabectedin, may be advantageous in patients with advanced sarcomas, if their drug response and performance status scores are good.

Anti-Tumor Effect and Neurotoxicity of Ethanol Adjuvant Therapy after Surgery of a Soft Tissue Sarcoma.

Wide resection is the main treatment for sarcomas; however, when they are located near major nerves, their sacrifices might affect limb function. The efficacy of ethanol adjuvant therapy for sarcomas has not been established. In this study, the anti-tumor effect of ethanol, as well as its neurotoxicity, were assessed. In vitro anti-tumor effect of ethanol as evaluated using MTT, wound healing, and invasion assays on a synovial sarcoma cell line (HS-SY-II). In vivo, an assessment was conducted in nude mice (implanted with subcutaneous HS-SY-II) treated with different ethanol concentrations after surgery with a close margin. Sciatic nerve neurotoxicity was assessed with electrophysiological and histological examination. In vitro, ethanol concentrations at 30% and higher showed cytotoxic effects in MTT assay and markedly reduced migration and invasive ability of HS-SY-II. In vivo, both 30% and 99.5% ethanol concentrations, compared to 0% concentration, significantly reduced the local recurrence. However, in the group treated with 99.5% ethanol, nerve conduction tests showed prolonged latency and decreased amplitude, and morphological changes suggestive of nerve degeneration were observed in the sciatic nerve, while the 30% ethanol did not cause neurological damage. In conclusion, 30% is the optimal concentration for ethanol adjuvant therapy after close-margin surgery for sarcoma.

Impact of the COVID-19 pandemic on bone and soft tissue tumor treatment: A single-institution study.

OBJECTIVE: The spread of coronavirus disease 2019 (COVID-19) has caused a great deal of damage to daily medical care. We investigated the impact of the COVID-19 pandemic on bone and soft tissue tumor treatment at our hospital. METHODS: We conducted a retrospective comparative study of two groups of patients at Osaka City University Hospital during the period of increasing COVID-19 infections (February-December 2020, group C) and the same period the previous year (February- December 2019, group NC). Clinical data, including patient's age, gender, type of tumor, neoplasms, number of surgical cases for inpatients and outpatients, operation time, use of implants, length of hospital stay, inpatient hospital costs, number of inpatients receiving anticancer drugs, and postoperative complications in these two groups were retrospectively evaluated. RESULTS: The number of cases of malignant bone and soft tissue tumors that were resected during hospitalization was predominantly higher in group C than in group NC (P = 0.01). There were no significant differences in operation time, use of implants, and postoperative complications between group C and group NC, but there were significant differences in the length of hospital stay and hospital costs (P<0.001). CONCLUSIONS: The COVID-19 pandemic has been recognized throughout the world to have adverse effects in a variety of areas. It had a negative impact on hospital costs and the length of hospital stay in the field of bone and soft tissue tumor treatment.

Pathological fracture of a solitary bone cyst in the calcaneus: a case series and literature review.

INTRODUCTION: Solitary bone cysts in the calcaneus (calcaneal bone cysts) are often asymptomatic. Pathological fractures are rare, and few reports are available concerning its risk assessment. Therefore, the indication for operative interventions remains debatable, and further discussion on the treatment of symptomatic cysts and pathological fractures in calcaneal bone cysts is necessary. MATERIALS AND METHODS: Clinical data of 21 patients with calcaneal bone cysts (16 men and five women) was retrospectively reviewed. The average age was 13.3 (range, 7-23) years. Clinical data, such as concerning symptoms, radiological findings, pathological findings and outcomes, were investigated, and the pathogenesis of symptomatic cysts was studied. RESULTS: Thirteen cysts were symptomatic, and eight were incidentally discovered. Computed tomography revealed no fracture in 12 cases, microfracture in eight and complete fracture in one. The areas under the curves of the receiver operating characteristic curves calculated to establish an association between cyst size and symptoms and cyst size and pathological fractures (microfracture and complete fracture) were 0.78 and 0.71, respectively. Symptomatic cysts and pathological fractures were associated with the cyst ratio (cyst size/calcaneus ≥ 0.20). On magnetic resonance imaging (MRI), fluid levels were observed in 11 of 21 (52%) patients. At the time of surgery, blood from the haemorrhage was aspirated from 15 of 21 (71%) cysts. CONCLUSIONS: Orthopaedic surgeons should be aware that the cyst ratio is associated with clinical symptoms and pathological fractures. MRI and gross findings revealed haemorrhage in the cystic fluid. In calcaneal bone cysts, repeated microfractures and spontaneous healing might occur.

High tartrate-resistant acid phosphatase (TRACP 5b) level in cystic fluid is a significant prognostic marker for postoperative recurrence in solitary bone cysts.

Purpose: The pathogenesis of cystic fluid storage in solitary bone cysts remains unclear. We aimed to compare the results of the biochemical analysis of cystic fluid with clinical findings. We identified a significant marker of postoperative recurrence. Methods: Twenty-seven male and eight female patients were studied; the median age at diagnosis was 11 (5-23) years. The mean follow-up period was 60 months (range: 14-146 months). Clinical information including sex, age, affected site, radiological findings of phase (active or latent), surgical procedure, outcome, and biochemical analysis of serum and cystic fluid was obtained. Results: The 5-year healing rate was 64.0%. Biochemical analysis revealed that total protein and albumin values in the cystic fluid were significantly lower, compared to those in the serum. Levels of bone turnover markers, such as alkaline phosphatase, bone-specific alkaline phosphatase, and tartrate-resistant acid phosphatase 5b were remarkably elevated in the cystic fluid than in the serum. R values were 0.127, 0.076, and 0.095 for alkaline phosphatase, bone-specific alkaline phosphatase, and tartrate-resistant acid phosphatase 5b, respectively. Areas under the receiver operating characteristic curves, calculated to assess the association of alkaline phosphatase, bone-specific alkaline phosphatase, and tartrate-resistant acid phosphatase 5b levels in the cystic fluid with postoperative recurrence, were 0.57, 0.51, and 0.70, respectively. Conclusions: No clear correlation of bone turnover marker levels between the serum and cystic fluid was observed. The high tartrate-resistant acid phosphatase 5b level in the cystic fluid was associated with postoperative recurrence. The bone resorption caused by osteoclasts is considered to affect postoperative recurrence. Level of evidence: Level IV.

Review of the referral documents of patients with malignant soft tissue tumors.

Fifteen years have passed since the soft tissue tumor practice guidelines were first published in Japan. Tumor size of ≥ 5 cm and tumor depth were key findings suggestive of malignant soft tissue tumors. We reviewed the referral documents provided by the referring physicians to see if these two findings were reported. The study was conducted from January 2007 to December 2021 and included 142 patients (83 men and 59 women; median age, 64 [6-94] years) with malignant soft tissue tumors. Patient referral documents from physicians were screened for descriptions of the tumor size and depth. The tumor size, depth, and both were described in 51.4%, 36.6%, and 23.2% of the referrals, respectively. Both findings were mentioned in 23.8%, 21.7%, and 25.0% of referrals in 2007-2011, 2012-2016, and 2017-2021, respectively. Of orthopedic surgeons and other physicians, 61.2% and 38.6%, respectively, described the tumor size. Whether the general physicians could follow the soft tissue tumor practice guidelines was difficult to conclude by reviewing patient referral documents. However, orthopedic surgeons seemed to pay more attention to tumor size. Awareness regarding soft tissue tumor practice guidelines should be increased to help diagnose malignant soft tissue tumors early.

Tumor-skin invasion is a reliable risk factor for poor prognosis in superficial soft tissue sarcomas.

INTRODUCTION: Superficial soft tissue sarcomas are often left untreated unless they invade the skin and skin ulcers manifest. Progressive sarcomas frequently result in dismal oncological outcomes despite multidisciplinary treatment. This study aimed to identify prognostic factors for superficial soft tissue sarcomas. MATERIALS AND METHODS: This study retrospectively analyzed the clinicopathological data of 82 patients with superficial soft tissue sarcomas treated between August 2003 and December 2020 at our institution. A superficial soft tissue sarcoma was defined if the percentage of the area occupied by the tumor in the assessed region (skin, subcutaneous) was more than 50%. Age, sex, location, tumor size, tumor-skin invasion, tumor grade, and distant metastasis at initial diagnosis were evaluated as potential prognostic factors. Cox proportional hazards regression models were used to identify the prognostic factors. Five-year survival rates were assessed by the Kaplan-Meier method. RESULTS: The mean follow-up time was 60.1 months. The 5-year overall survival, 5-year local recurrence-free survival, and 5-year metastasis survival rates were 76.4%, 60.6%, and 71.0%, respectively. Univariate analysis showed significant relationships between poor prognosis and tumor size ≥5 cm, distant metastasis at initial diagnosis, and tumor-skin invasion. In the multivariate analysis, only the tumor-skin invasion was associated with worse overall survival. CONCLUSIONS: Superficial soft tissue sarcomas have biologically been considered a separate category due to their better prognosis. In this study, the tumor-skin invasion was the only significant factor associated with a poor prognosis. Therefore, all superficial soft tissue sarcomas without tumor-skin invasion should be treated as early as possible.

Does Systemic Chemotherapy Influence Skeletal Growth of Young Osteosarcoma Patients as a Treatment-Related Late Adverse Effect?

The aim of this study was to investigate the influence of systemic chemotherapy on the skeletal growth of young osteosarcoma patients as a treatment-related late adverse effect. We reviewed the height data of 20 osteosarcoma patients (13 males and 7 females) aged ≤18 years. The average (±SD) age at diagnosis was 14.5 (±3.3) years. The average follow-up interval was 89.6 months. After wide resection of the affected bones, reconstruction with tumor prostheses and auto-bone grafting was carried out in 11 and 9 cases, respectively. Pearson's correlation coefficient was calculated to evaluate the association between actual and predicted (using Paley's multiplier method) heights. Z-scores were used to compare the initial and final heights with the Japanese national growth curve. Actual and predicted heights were correlated according to Pearson's correlation coefficient (R = 0.503). Z-analysis showed that statistical significance (p = 0.04) was noted for the height data Z-scores of patients between ≤10 years and >10 years at the final follow-up. Systemic chemotherapy did not reduce skeletal growth in young osteosarcoma patients as a late adverse effect based on two different evaluation methods. However, patients aged ≤10 years at diagnosis may develop a short stature after systemic chemotherapy.

Efficacy of Pazopanib in the Treatment of Metastatic Malignant Giant Cell Tumor of Soft Tissue: A Case Report.

Giant cell tumor of soft tissue (GCT-ST), histologically resembling the GCT of the bone, is a rare tumor. The tumor has been categorized to have low malignancy. Few reports of local recurrence or distant metastasis and the use of chemotherapeutic agents for metastatic GCT-ST exist. Herein, we report the efficacy of pazopanib in a 78-year-old Japanese woman with GCT in the intrinsic back musculature with both post-operative local recurrence and lung metastasis. The patient visited the hospital with a three-month history of a palpable mass in the intrinsic back musculature. Following magnetic resonance imaging, the tumor predominantly exhibited slight hyperintensity on T2-weighted images and intense heterogeneous enhancement on contrast-enhanced T1-weighted images. A percutaneous needle biopsy was performed, and the pathological diagnosis was GCT-ST. The patient underwent surgery, and three months later she presented with not only local recurrence but also multiple lung metastases. The patient was immediately treated with pazopanib 400 mg once daily. One month after initiating treatment, a partial response in the pulmonary lesions was observed, and stable disease (SD) effects lasted for 11 months without severe adverse effects. Therefore, pazopanib treatment for metastatic malignant giant cell tumor of soft tissue achieved reasonable success.

Finite Element Analysis Could Predict and Prevent a Pathological Femoral Shaft Fracture after En Bloc Resection of a Large Osteoid Osteoma.

Osteoid osteoma is a benign tumor. Approximately 20% of these tumors are located in the femur. The tumor primarily occurs in children and is treated by surgical excision or radiofrequency ablation. Recently, bone-tumor resection using three-dimensional (3D) intraoperative imaging with an O-arm in combination with a navigation system has been reported to be effective. However, there is a risk of postoperative fracture because of the weakening of the bone after drilling for tumor resection. A 12-year-old Japanese girl presented with an osteoid osteoma in the left femoral shaft, which resulted in a fracture after en bloc resection and artificial bone grafting using a 3D image-guided (O-arm) assisted navigation system. Orthopedic oncologists should be aware of the risk of fracture. Moreover, they should consider the mechanical risk prediction of bone fracture using finite element analysis prior to treatment.

Prediction of Risk Factors for Pathological Fracture After Bone Tumor Biopsy Using Finite Element Analysis.

PURPOSE: We aimed to determine if finite element analysis (FEA) provides useful thresholds for bone biopsy practice patterns. METHODS: The femoral head compression test was performed on rabbit femurs, using FEA to identify the part of the bone that preferentially fractures (n=15/group). Four types of rectangular biopsy holes were made using finite element (FE) models. These models were divided into control (no defect), defect 1 (10% width), defect 2 (20% width), defect 3 (30% width), and defect 4 (40% width) groups (n=15 each). Three types of rectangular biopsy holes (defect A, 27% length; defect B, 40% length; defect C, 53% length) were also made using FE models (n=15 each). The load to failure was then predicted using FEA. RESULTS: Almost all femurs with no defect were fractured at the femoral shaft in both the femoral head compression test and FEA. The experimental load to failure in intact femurs was predicted well by the FE models (R2=0.74, p<0.001). There was also a strong linear correlation of stiffness between compression test in femurs with no defect and the FEA (R2=0.68, p<0.001). Therefore, the femoral shaft was targeted for FEA. The median predicted loads by FEA were significantly higher for defect 1 than for the other types when testing the widths of the rectangular defects, but there were no significant differences among the three types when testing for defect length. CONCLUSION: The FEA results correlated well with those of the femoral head compression test. A width <10% of the circumference length in bone biopsy holes helps minimize bone strength reduction using FEA. It may be useful for orthopedic doctors to perform FEA to avoid pathological fractures after bone tumor biopsy.

Risk Assessment for Pathological Fracture After Bone Tumour Biopsy.

AIM: This study aimed to identify the risk of pathological fractures after bone tumour biopsy. MATERIALS AND METHODS: Fifty rabbit femurs were divided into groups according to defect size: Control (no defect), type 1 (10% width), type 2 (20% width), type 3 (30% width), and type 4 (40% width). Another 20 were also divided into control, type A (27% length), type B (40% length), and type C (53% length) groups. Performing femoral head compression testing allowed each parameter (maximum load, displacement, elastic modulus, and fracture energy) to be calculated individually. RESULTS: Compressive maximum load was significantly higher for type 1 than for the other types when testing rectangular defects of different widths, while there were no significant differences between the three types when testing by defect length. CONCLUSION: It may be useful for orthopaedic oncologists to make a rectangular biopsy hole with a width measuring less than 10% of the circumference and to enlarge the hole longitudinally to avoid pathological fracture.

Investigation of multiple primary cancers in patients with bone and soft tissue primary malignancies: A retrospective, institution-based study.

In the aging society in Japan, the occurrence of multiple primary cancers has recently increased due to an increase in life expectancy and increased development in cancer diagnostic technology and improvement in treatment outcomes. However, few reports have focused on multiple primary cancers in patients with bone and soft tissue tumors. The present study aimed to analyze the clinical characteristics of patients with multiple malignancies of the bone and soft tissue. Between April 2008 and April 2017, among 973 patients treated at the Department of Orthopedic Surgery, Osaka City University Hospital, those with multiple primary cancers involving bone and soft tissue were identified. The number of cases with multiple cancers in the present study was 30/973 (3.08%), including 21 males and 9 females. The median age at diagnosis of patients with bone and soft tissue sarcoma was 73.5 years (range, 7-83 years). There were 22 patients with double cancers, and 5, 2 and 1 patients with triple, quadruple and quintuple cancers, respectively. Colorectal cancer was the most common primary cancer (n=9). In total, 28.6% of patients had simultaneous cancer, while 71.4% of patients had heterochronous cancer. The overall 5-year survival for all patients was 75.6%. The prognosis of patients with double cancer of bone and soft tissue sarcoma was not necessarily poor. However, it is necessary to pay attention to the possibility of secondary malignancy. Therefore, it is essential to be careful and well organized when selecting treatment modalities and to adopt a logistical approach for the care of patients with ongoing multiple malignancies.

Promising abscopal effect of combination therapy with thermal tumour ablation and intratumoural OK-432 injection in the rat osteosarcoma model.

Treatment options for metastatic osteosarcoma are limited. The present study aimed to evaluate whether radiofrequency ablation (RFA) combined with intratumoural OK-432 injection induces systemic anti-tumour immunity in rat osteosarcoma model. Eighty of 145 rats were assigned to four groups to evaluate overall survival and tumour size: control (no treatment), RFA-only, OK-432, and RFA-OK-432. The remaining 65 were assigned for histological examination. Maximum diameters of tibial and lung tumours were determined. Tumour samples were histologically examined using haematoxylin-eosin and immunohistochemical staining. Overall survival was significantly prolonged in the RFA-OK-432 group compared to the RFA-only and OK-432 groups. Only rats in the RFA-OK-432 group exhibited significant decreases in maximum tumour diameter after treatment. Ki-67-positive tumour cells in the RFA-OK-432 group were significantly stained negative on immunohistochemical analysis as opposed to those in the RFA-only and OK-432 groups. The number of CD11c+, OX-62+, CD4+, and CD8 + cells significantly increased in the RFA-OK-432 group compared to the RFA-only group. RFA with intratumoural OK-432 injection resulted in distant tumour suppression, prolonged survival, and increased dendritic cells, cytotoxic T cells, IFN-γ, and TNF-α, whereas RFA or OK-432 alone did not produce this effect. This combination may induce an abscopal effect in human osteosarcoma.

Clinical significance of thermal detection of soft-tissue tumors.

BACKGROUND: Soft-tissue tumors are often accompanied by abnormal temperature distribution detected during palpation. However, the assessment of temperature distribution is subjective, limiting its wide use in cancer screening. The aim of this study was to evaluate the clinical significance of the thermal detection of soft-tissue tumors. METHODS: This study involved 100 soft-tissue tumor patients, the pathological diagnosis of which was confirmed by surgery from February 2017 to March 2019 in our hospital. Sixty patients were diagnosed with benign lesions, while 40 patients had malignant tumors. The cohort consisted of 52 males and 48 females, with a median age of 62 (range 22-84). Temperature difference detection by orthopedic oncologists, as well as the consistency and accuracy of temperature distribution detection by orthopedic oncologists, were investigated. The relationship between abnormal temperature distribution and the presence of malignancy in soft tissue was also explored. RESULTS: We found that more than half of the orthopedic oncologists could detect a temperature difference of 0.2 °C or higher. All three surgeons reported consistent temperature distribution findings after palpation in 92 out of 100 soft-tumor patients. The presence of abnormal temperature distribution was significantly associated with the presence of malignancy (P < 0.0017). Temperature differences of 0.2 °C or higher were significantly associated with the presence of malignant tumors (P < 0.001). CONCLUSIONS: Diagnosis of abnormal temperature distribution by orthopedic oncologists could suggest the presence of malignancy in patients with soft-tissue lesions.

Successful pre-operative local control of skin exposure by sarcoma using combination of systemic chemotherapy and Mohs' chemosurgery.

BACKGROUND: Sarcomas sometimes invade the skin and become exposed, producing malignant wounds characterized by bleeding, exudate, odor, and infection. Malignant cutaneous sarcomas are generally incurable and ultimately impair patients' quality of life. Mohs' chemosurgery is a previously published technique for chemical fixation of a cutaneous tumor and subsequent excision. CASE PRESENTATION: We present the case of a 44-year-old man with an undifferentiated pleomorphic sarcoma arising in the right chest wall and rupturing through the skin. The tumor manifested as a malignant wound with ulceration, bleeding, exudate, and a strong odor. Treatment with systemic chemotherapy and Mohs' chemosurgery was initiated. After repeated courses, the tumor demonstrated significant shrinkage. We were then able to perform wide resection and reconstruction with a rectus abdominis musculocutaneous flap. Pathologic examination of the resected specimen confirmed negative margins. CONCLUSIONS: Mohs' chemosurgery with concurrent systemic chemotherapy is an effective and reliable treatment option for achieving pre-operative local control of sarcomas that rupture through the skin.

Possible pathogenesis of calcaneal bone cysts.

INTRODUCTION: Recent literature indicates that calcaneal bone cysts have different clinical features compared to long bone cysts. Yet, previous studies have mainly focused on pathogenesis of long bone cysts. In this study, the pathogenesis of calcaneal bone cysts was investigated from radiological and pathological findings. MATERIALS AND METHODS: Patients comprised 18 males and 6 females diagnosed with calcaneal bone cysts at a median age ± standard deviation of 13.0 ± 3.6 years. Plain radiographs, computed tomography, magnetic resonance imaging, cystography, bone scintigraphy, and pathology were reviewed. RESULTS: All cysts occupied the central triangular area of the bone, with six extending posteriorly and two developing anteriorly. Fifteen of 20 cases (75%) showed the expanded foramen structures at the anterior margin of the posterior facet. According to cystography, four cysts showed absence of leakage to subtalar joint. Cystic fluid caused chronic haemorrhaging in 18 cases and pathologically detected cholesterol clefts were noted in 14 cases. DISCUSSION: The location of the expanded foramen structures was consistent with the nutrient foramens of the sinus tarsi artery in the unaffected population. Hence, initial cysts may originate from the collapse of the sinus tarsi artery. Subsequent haemorrhage may extend into the central triangle area, which is biomechanically free of stress. Because of poor bone remodelling, degenerative change of the haemorrhage is prolonged. The results of this study showed that circulation collapse of the sinus tarsi artery and mechanical factors are important in the formation of calcaneal bone cysts.

Exploration of the Optimal Shape for Bone Tumour Biopsy.

BACKGROUND/AIM: Biopsy hole for bone tumour biopsy may cause pathological fractures. This study aimed to identify the optimal shape of bone tumour biopsy hole using the rabbit femoral head compression test to avoid pathological fracture. MATERIALS AND METHODS: A compression test with no defect was performed to identify bone fracture location. Three shapes of biopsy holes (same size) were made artificially. Sixty rabbit femurs were randomly divided (n=15 each) into control (no defect), Shape 1 (round), Shape 2 (square), and Shape 3 (rectangular) groups. RESULTS: Twelve out of fifteen femurs were fractured on the femoral shaft; the femoral shaft was targeted for the compression test. Compressive maximum load and fracture energy were significantly higher for Shape 3 than for the other Shapes. CONCLUSION: A rectangular biopsy hole helps minimise reduction in bone strength. The defect width may be related to fragility of the affected bone.

Clinical course of soft tissue sarcomas presenting as malignant wounds.

BACKGROUND: Soft tissue sarcomas can invade the skin and occasionally present as malignant wounds characterized by bleeding, exudate, odor, and infection. This study aimed to highlight the clinical problems associated with sarcomas with malignant wounds. METHODS: The patient group comprised 12 males and 1 female, with a median age at diagnosis of 75 (range 23-95) years old. The average follow-up was 28.3 months. Clinical information concerning the patients with soft tissue sarcomas presenting as malignant wounds was retrospectively investigated. RESULTS: Eleven out of 13 malignant wounds cases were male and over 65 years old. Tumors were located in the chest wall in 4 patients and the thigh in 4, respectively. The histology was high-grade in 12 patients. Persistent bleeding from malignant wounds was observed in 6 patients. The patients' pre-operative hemoglobin level was 7.5 ± 1.9 g/dl. For the purpose of temporary hemostasis, Mohs' paste was applied in 1 case and zinc oxide starch was applied in 3. Surgical removal was done in 10 patients, and amputation in 2. Six patients needed skin reconstruction. Post-operative surgical site infection was found in 5 patients, but the infection did not occur in the patients who underwent skin reconstruction of musculocutaneous flaps. The 5-year survival rate was 25.4%. CONCLUSIONS: Massive bleeding from the tumor impairs patients' quality of life and can be life-threatening. To avoid exacerbating the systemic condition of elderly cancer patients, urgent surgical removal is recommended, especially in cases of exposed tumors with persistent bleeding. Orthopedic oncologists should be aware of surgical site infection as a potential post-operative complication.

Secondary osteosarcoma in patients previously treated for childhood cancer: Three case reports.

The prognosis of childhood cancers has improved markedly, and the proportion of long-term survivors has increased in recent years. However, with the increase in the number of long-term survivors, the development of latent treatment-related adverse effects, such as secondary malignancies, has generated new problems. Secondary cancer is defined as a histologically distinct malignancy that develops at least 2 months after the completion of treatment for primary cancer. Genetic factors and acquired conditions associated with treatment modalities are possible causes of secondary malignancy development. Genetic factors include the presence of Li-Fraumeni syndrome (LFS) and retinoblastoma. In terms of acquired factors, radiation and chemotherapy have been reported to be the most strongly associated with secondary malignancy development. The use of alkylating agents and topoisomerase II inhibitors for the treatment of childhood cancer increases the subsequent risk of secondary tumors. We herein investigated three cases of secondary osteosarcoma several years after treatment for primary cancer. In the three patients, the familial history did not appear to fit the clinical diagnostic criteria of LFS or retinoblastoma. The patients had not received previous radiation therapy to the anatomical site of the secondary cancer. However, high dosages of alkylating agents and topoisomerase II inhibitors had been administered for the treatment of primary cancer. The exact link between chemotherapy and secondary cancer remains elusive, but the possibility of an association should be considered. Following the development of multidisciplinary therapies, long-term follow-up and monitoring of latent adverse effects may be necessary for childhood cancer survivors.