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Background Soft tissue sarcomas are a diverse group of rare malignant tumours, mostly occurring in the lower extremities. Amputations are necessary for achieving local control when the soft tissue sarcomas are too large and/or have neurovascular involvement. Patients who require amputation have a poorer prognosis than those who undergo limb-salvage surgery. Patients and Methods We investigated the tumour characteristics and the clinical outcomes in 55 patients with primary soft tissue sarcomas, who underwent amputation. We excluded patients with amputation performed distal to the wrist or ankle joints and those with recurrent soft tissue sarcomas. Results The mean tumour size was 11.1 cm. Hip disarticulation was performed in 6 patients, 20 underwent above the knee amputation, 8 underwent knee disarticulation and 12 underwent below the knee amputation. Shoulder disarticulation was performed in three patients, five underwent above the elbow amputation, and one underwent below the elbow amputation. The 5-year disease-specific survival rate was 52.8%. The 5-year recurrence-free survival rate and 5-year metastasis-free survival rates were 90.1% and 38.5%, respectively. Larger tumour size, age and the distant metastases at first presentation were predictors of poor prognosis for survival in multivariate analysis. Twenty-eight patients could walk using artificial limbs. The level of amputation (above versus below the knee) showed a significant difference in achieving independent gait. Conclusion Amputation is a useful treatment option for achieving local control in patients with large soft tissue sarcomas. Patients had an opportunity of walking, especially for those who underwent below the knee amputation.

AimsThe aim of this study is to evaluate the clinical results of operative intervention for femoral metastases which were selected based on expected survival and to discuss appropriate surgical strategies.MethodsFrom 2002 to 2017, 148 consecutive patients undergoing surgery for femoral metastasis were included in this study. Prognostic risk assessments were performed according to the Katagiri and revised Katagiri scoring system. In general, the low-risk group underwent resection and reconstruction with endoprosthetic replacement (EPR), while the high-risk group underwent internal fixation (IF) and radiation therapy. For the intermediate-risk group, the operative choice depended on the patient’s condition, degree of bone destruction, and radio-sensitivity. Overall survival, local failure, walking ability, and systemic complications were evaluated.ResultsA total of 83 patients underwent EPR (low-risk, 23%; intermediate-risk, 60%; high-risk, 17%) and 65 patients underwent IF (low-risk, 0%; intermediate-risk, 32%; high-risk, 68%). The one-year survival rate was 71% for EPR and 15% for IF (p < 0.001). The one-year local failure-free survival was 93% for EPR and 67% for IF, and the two-year and five-year local failure-free survival for EPR were both 88% (p = 0.016). Although the ambulatory rate was 99% for EPR and 60% for IF, the median time to ambulation was shorter in the IF (EPR, 28 days, interquartile range (IQR) 25 to 35; IF, 23 days, IQR 18 to 28; p < 0.001) The cause of non ambulation was mainly due to progression of cancer (89%). The rate of systemic complications was comparable between the two groups (EPR, 18%; IF, 22%; p = 0.598).ConclusionSelective use of EPR where survival is expected to be good offers correspondingly good long-term results. IF is less invasive with shorter treatment period, which is beneficial for patients with short-term expected survival. Prognosis is an important indicator in selecting operative procedures for femoral metastasis. Cite this article: Bone Joint J 2020;102-B(3):285–292

Purpose The role of chemotherapy (CT) and radiotherapy (RT) for management of extraskeletal osteosarcoma (ESOS) remains controversial. We examined disease outcomes for ESOS patients and investigated the association between CT/RT with recurrence and survival. Patients and methods Retrospective review at 25 international sarcoma centers identified patients ≥18 years old treated for ESOS from 1971 to 2016. Patient/tumour characteristics, treatment, local/systemic recurrence, and survival data were collected. Kaplan–Meier survival and Cox proportional-hazards regression and cumulative incidence competing risks analysis were performed. Results 370 patients with localized ESOS treated definitively with surgery presented with mainly deep tumours (n = 294, 80%). 122 patients underwent surgical resection alone, 96 (26%) also received CT, 70 (19%) RT and 82 (22%) both adjuvants. Five-year survival for patients with localized ESOS was 56% (95% CI 51%–62%). Almost half of patients (n = 173, 47%) developed recurrence: local 9% (35/370), distant 28% (102/370) or both 10% (36/370). Considering death as a competing event, there was no significant difference in cumulative incidence of local or systemic recurrence between patients who received CT, RT, both or neither (local p = 0.50, systemic p = 0.69). Multiple regression Cox analysis showed a significant association between RT and decreased local recurrence (HR 0.46 [95% CI 0.26–0.80], p = 0.01). Conclusion Although the use of RT significantly decreased local recurrences, CT did not decrease the risk of systemic recurrence, and neither CT, nor RT nor both were associated with improved survival in patients with localized ESOS. Our results do not support the use of CT; however, adjuvant RT demonstrates benefit in patients with locally resectable ESOS.

Background Chondroblastomas are rare, benign, locally aggressive lesions that appear in the epiphysis. Surgery for femoral head chondroblastoma (FHCB) is difficult. Conventional treatment with curettage via a drilled tunnel along the femoral neck can damage the growth plate and is associated with high local recurrence rates. The trapdoor procedure, which directly facilitates lesion access from the femoral head articular surface, can reduce local recurrence and avoid growth plate damage, although it requires surgical dislocation. Little is known about the long-term results of this direct articular surface approach, and there are no case reports on trapdoor procedures without dislocation. Case presentation We report two cases (patients aged 12 and 15 years) of FHCB presented with coxalgia treated using the trapdoor procedure without surgical dislocation. Both surgeries were performed with patients in the semi-lateral position. The hip joint was exposed via an anterior approach, and a capsulotomy was performed at the superior rim of the acetabulum, followed by the external rotation of the hip joint. With a fine osteotome, a rectangular flap (trapdoor) was opened on the cartilage surface in the lateral non-weight-bearing area, and curettage of the lesion followed by bone and/or bone substitute grafting was performed. Subsequently, the trapdoor was replaced in its original position. There has been no local recurrence or femoral head aseptic necrosis after more than 6 and 12 years for patients 1 and 2, respectively. Both patients had musculoskeletal tumor society scores of 100% at follow-up and are enjoying a normal active life. Conclusions This direct femoral head approach without dislocation may be a simple treatment alternative for FHCB.

Pro-gastrin-releasing peptide (ProGRP) is an established tumor marker of small cell lung cancer. The purpose of this study was to determine if ProGRP could serve as a tumor marker for the Ewing sarcoma family of tumors (ESFTs). Sixteen patients with ESFTs (mean age 32 years) were included in this study. As a control group, 42 patients with other tumor types that clinically or pathologically mimic ESFTs were also analyzed. Pre-treatment serum ProGRP and neuron-specific enolase (NSE) levels, the relationships between these levels, and tumor volume were investigated. In addition, serial changes in the serum or plasma ProGRP (6 patients) and NSE levels (5 patients) were measured over the course of treatment. Pre-treatment serum ProGRP levels were higher than the normal range in 8 of 16 patients; for these eight patients, ProGRP levels positively correlated with tumor volume (R = 0.99). In the control group, ProGRP levels were within the normal range, except for the two patients. Changes in ProGRP levels during treatment were consistent with tumor volume. Serum NSE levels were elevated in 14 of 16 patients with ESFTs and 8 of 42 patients with other tumor types. The range of NSE elevation was much smaller compared to that of ProGRP. Our data indicate that ProGRP is superior to NSE in terms of specificity. Serum ProGRP levels were elevated in half of the patients with ESFTs and reflected therapeutic response. ProGRP is a reliable tumor marker for the diagnosis of ESFTs and evaluation of treatment response.

Although the unpredictable malignant behavior of solitary fibrous tumors (SFTs) has been recognized, the clinical features and prognosis of metastatic SFTs have not been well documented due to the extreme rarity of these cases. The aim of this study is to investigate the clinical features, prognostic factors, and optimal management of patients with metastatic SFTs. Sixty patients with metastatic SFT were retrospectively reviewed. Univariate and multivariate analyses were performed to identify the factors associated with survival. Time to next treatment (TNT) was used to evaluate the effects of various chemotherapy regimens. A total of 34 male and 26 female patients (median age 55 years, range, 23–87 years) were included in the study. The median follow-up period after metastasis was 32 months (range 1–126 months). Tumor location and local recurrence were correlated with late metastasis. The 3- and 5-year overall survival rates were 72.7% and 49.2%, respectively. Primary tumor location, number of metastases, and metastasectomy were significantly associated with survival. Metastasectomy was the only significant variable on multivariate analysis. The TNT was significantly different among the various regimens. Patients with metastatic SFTs had relatively longer survival periods compared with those with other metastatic soft-tissue sarcomas. Tumor location and number of metastases was associated with survival. Surgical resection of the metastatic lesions offers the best chance of survival, however further studies are warranted to define patients who would benefit from metastasectomy, and the most effective chemotherapeutic regimen for patients with metastatic SFTs remains unknown.

The aim of this study is to evaluate the clinical results of operative intervention for femoral metastases which were selected based on expected survival and to discuss appropriate surgical strategies.From 2002 to 2017, 148 consecutive patients undergoing surgery for femoral metastasis were included in this study. Prognostic risk assessments were performed according to the Katagiri and revised Katagiri scoring system. In general, the low-risk group underwent resection and reconstruction with endoprosthetic replacement (EPR), while the high-risk group underwent internal fixation (IF) and radiation therapy. For the intermediate-risk group, the operative choice depended on the patient's condition, degree of bone destruction, and radio-sensitivity. Overall survival, local failure, walking ability, and systemic complications were evaluated.A total of 83 patients underwent EPR (low-risk, 23%; intermediate-risk, 60%; high-risk, 17%) and 65 patients underwent IF (low-risk, 0%; intermediate-risk, 32%; high-risk, 68%). The one-year survival rate was 71% for EPR and 15% for IF (p0.001). The one-year local failure-free survival was 93% for EPR and 67% for IF, and the two-year and five-year local failure-free survival for EPR were both 88% (p = 0.016). Although the ambulatory rate was 99% for EPR and 60% for IF, the median time to ambulation was shorter in the IF (EPR, 28 days, interquartile range (IQR) 25 to 35; IF, 23 days, IQR 18 to 28; p0.001) The cause of non ambulation was mainly due to progression of cancer (89%). The rate of systemic complications was comparable between the two groups (EPR, 18%; IF, 22%; p = 0.598).Selective use of EPR where survival is expected to be good offers correspondingly good long-term results. IF is less invasive with shorter treatment period, which is beneficial for patients with short-term expected survival. Prognosis is an important indicator in selecting operative procedures for femoral metastasis. Cite this article

Several types of soft tissue sarcomas have peripheral infiltrative growth characteristics called tail-like lesions. The efficacy of neoadjuvant therapy for tumors with tail-like lesions has not been elucidated. From 2012 to 2019, we analyzed 36 patients with soft tissue sarcoma with tail-like lesions treated with neoadjuvant therapy, including chemotherapy, radiotherapy, or both. The effect of neoadjuvant therapy on the tail sign was investigated by analyzing the change in tail-like lesions during neoadjuvant therapy and histological responses. The median length of the tail-like lesion reduced from 29.5 mm at initiation to 19.5 mm after neoadjuvant therapy. The extent of shrinkage in tail-like lesions was related to the histopathological responses in the main part of the tumor. Complete disappearance of the tail-like lesion was observed in 12 patients, however, it was not related to achieving a microscopically negative margin. The oncologic outcomes did not significantly differ between cases with and without the complete disappearance of tail-like lesions. This study indicated that the shrinkage of tail-like lesions did not have a significant effect on complete resection or improvements of clinical outcomes. A more comprehensive evaluation is needed to elaborate on the surgical strategy.

We analyzed 428 femoral metastases initially treated with radiotherapy between 2002 and 2011 to clarify the clinical details of post-irradiation fractures of femoral metastasis. Patients included 161 men and 167 women, with a mean age of 62 years. Fracture incidence, fracture site, fracture risk based on X-ray images before radiotherapy, and interval from completion of radiotherapy to fracture occurrence were assessed. In addition, 24 pathological specimens obtained during 27 surgeries for these fractures were examined. Fractures occurred in 7.7% of 428 femoral metastases (total 33: 28 actual fractures and five virtual fractures with progressive pain and bone destruction). The fracture rate was 7.8% in the proximal femur and 1.5% in the shaft (P = 0.001). Fractures occurred a median of 4.4 months after radiotherapy, with 39.4% occurring within 3 months and 63.6% within 6 months. Among femurs with high fracture risk according to Harrington’s criteria or Mirels’ score, the fracture rate was 13.9% and 11.8%, respectively. Viable tumor cells were detected in all five patients with painful virtual fracture, in 85.7% of femurs with actual fractures that occurred within 3 months, and in only 25.0% of actual fractures occurring after 3 months. Post-irradiation fractures of femoral metastasis most frequently occurred within 3 months after radiotherapy, and were more common in the peritrochanteric area than in the shaft. Radiological evidence of impending fracture did not correlate with a high fracture rate. Actual fractures occurring after more than 3 months were likely caused by post-irradiation fragility of the femur, without viable tumor cells.

Background Although initial trabectedin (1.2 mg/m2 ) is safe and effective for patients with translocation-related sarcoma (TRS) in Japan, its efficacy in other types of soft-tissue sarcomas (STSs) remains unknown. This study retrospectively investigated its efficacy and safety through postmarketing surveillance of trabectedin in patients with unresectable and relapsed STS. Methods One hundred forty patients received intravenous trabectedin (1.2 mg/m2 on day 1 every 21 days) over the course of 24 hours. The primary endpoint was the efficacy and safety of trabectedin. Results Grade 3 or higher adverse events occurred in 100 patients (71%) and included hepatotoxicity (37.8%), neutropenia (32.8%), and rhabdomyolysis (3.6%). Patients at high risk for grade 3 or higher rhabdomyolysis (36%) were classified by height (≥170.3 cm) and age (≤32 years) through a classification and regression tree model (area under the curve, 0.9). The overall median progression-free survival (PFS) was 3.7 months; with respect to the histological type, the median PFS was 17.4 months for myxoid liposarcoma, 4.9 months for leiomyosarcoma, 5.6 months for synovial sarcoma, and 3.7 months for dedifferentiated liposarcoma. Histological type (liposarcoma/leiomyosarcoma [L-sarcoma] and TRS) and grade 3 neutropenia (but not grade 4) were associated with significantly improved PFS after trabectedin treatment (P = .003, P = .04, and P = .001). The median growth modulation index (GMI) was 0.91; 37 patients (36.7%) experienced a GMI > 1.33, and among patients with solitary fibrous tumors and undifferentiated pleomorphic sarcoma, 60% and 42.9%, respectively, had a GMI > 1.33. The median overall survival (OS) was 16.4 months. A GMI > 1.33 was associated with significantly improved OS (P = .0006). Conclusions Initial trabectedin at 1.2 mg/m2 has clinically meaningful benefits for patients with L-sarcoma and certain histological subtypes of TRS.

Skeletal-related events (SRE) are common in patients with renal cell carcinoma (RCC) that includes bone metastasis. The purpose of this study was to clarify the effectiveness of zoledronate with and without sunitinib, combined with radiotherapy, for the treatment of bone metastasis from RCC. We retrospectively analyzed 62 RCC patients with bone metastasis, who had been treated with radiotherapy at our institution. We divided the study cohort into two groups: patients treated with radiotherapy alone (RT; n = 27) and those treated with radiotherapy combined with zoledronate (RT + Z; n = 35). We investigated the overall survival and post-irradiation (PI)-SRE-free rate for each group, as well as the effect of sunitinib in the RT + Z treatment group. In addition, we determined treatment effectiveness by imaging assessments and relative response rates. There was no significant difference in the survival rates between the RT and RT + Z treatment groups (p = 0.11). However, the PI-SRE-free rate in the RT + Z group was significantly higher than that in the RT group (p = 0.02). The PI-SRE-free rate was significantly higher in patients who were treated with sunitinib after radiotherapy than in those who were treated without sunitinib (p = 0.03). However, there was no significant difference in the relative response rates, as assessed by imaging, in each group. Radiotherapy combined with zoledronate is an effective treatment for RCC with bone metastasis to prevent PI-SRE. Sunitinib may reduce PI-SRE if used after radiotherapy and combined with zoledronate.

Osteosarcoma is the second most common primary malignant bone tumor, after multiple myeloma. It typically affects the metaphyseal part of the long bones, with the knee being affected in almost 50 % of cases [1]. Osteosarcoma is usually treated with chemotherapy combined with wide resection. Currently, the 5-year survival rate is reported to be around 70 % [2, 3]. Osteosarcoma rarely arises in the pelvis, but when it does, it often brings about severe intractable pain. However, the clinical results of surgery for pelvic osteosarcoma are disappointing because of the serious functional disability after surgery and the low survival rate [2, 4, 5]. We herein report a case of large pelvic osteosarcoma that was successfully treated with repetitive intra-arterial chemotherapy combined with radiotherapy. It is more than 21 years from the first presentation and the patient has been disease free for the last 7 years. The patient was informed that the data concerning the case would be submitted for publication, and she consented. Case report

SummaryPosterior reversible encephalopathy syndrome (PRES) is a clinical entity characterized by acute neurological symptoms such as severe headache, seizures, and visual disturbance, and by typical reversible lesion on brain magnetic resonance (MR) images. Since PRES is thought to be caused by vascular endothelial injury due to cytotoxic agents or acute systemic hypertension, the number of reports on PRES associated with angiogenesis inhibitors has been increasing. Although five cases that developed PRES due to pazopanib for renal cell carcinoma have already been reported, none of PRES due to pazopanib for soft-tissue sarcoma has been reported thus far. We describe a case of a 49-year-old woman with retroperitoneal soft-tissue sarcoma who developed PRES during pazopanib administration. Pazopanib at 800 mg/day was administered as her third-line treatment at relapse. After 38 days of pazopanib, she was admitted to our hospital with severe headache, vomiting, and systemic hypertension. The next day, she developed consciousness deterioration and visual disturbance together with exacerbated systemic hypertension. Brain MR images revealed hyper-intense signals on FLAIR sequences in the bilateral occipital lobes and the left thalamus. Intravenous nicardipine injection was immediately started to control her blood pressure and pazopanib was discontinued. Her symptoms gradually improved and disappeared on the fifth hospital day. After 2 weeks, hyper-intense signals on a FLAIR sequence disappeared completely. She restarted a low dose of pazopanib under good blood pressure control and experienced no subsequent recurrence of PRES.

The purpose of this study was to investigate the differences between spinal metastasis and osteoporotic compression fractures on plain X-ray images, focusing on asymmetrical vertebral collapse and fracture level.This study included 180 patients with pathological collapse from spinal metastasis (188 vertebrae) who were treated at our institution and 70 patients (92 vertebrae) with osteoporotic compression fractures. Anteroposterior X-ray images of the lower thoracic and lumbar spine were evaluated for asymmetrical collapse deformity.Asymmetrical collapse was found in 134 vertebrae (71.3%) with metastasis, and in 20 osteoporotic vertebrae (21.7%); this difference was significant (p 0.0001). The asymmetrical collapse angle in spinal metastasis patients ranged from 0 to 18°, with a mean of 7.0 and a standard deviation (SD) of 4.5. In contrast, the asymmetrical collapse angle in patients with osteoporotic fractures ranged from 0 to 13°, with a mean of 3.1 and a SD of 2.8. The difference in collapse angle between the two groups was statistically significant (p 0.001). The cutoff value to suspect spinal metastasis was determined to be 5° or more (sensitivity 0.67, specificity 0.74). Fracture at Th10 or below L3 was found in 20.2% of spinal metastasis patients; only 3% of osteoporotic fractures occurred at these levels.Asymmetrical collapse with an angle of 5° or more and fractures at atypical levels on plain radiographs can be useful clues to spinal metastasis.

Squamous cell carcinoma (SCC) is a common skin cancer that may be associated with ultraviolet ray exposure, scarring due to a trauma or burn, or chronic osteomyelitis [1, 2]. SCC is usually treated by surgery. However, for SCC of the lower legs, surgery is sometimes problematic; indeed, tumour cells easily infiltrate the tibia due to a lack of protective fat buffer layer at the front of the lower leg. Amputation may be a safe method for resecting the tumour, and management of the wound after the [...]

Chondroblastoma is a rare benign chondroid bone tumor, which typically arises from the epiphysis of a long tubular bone. We present a 13-year-old girl with persistent hip synovitis caused by a chondroblastoma that arose from the femoral neck (metaphysis) and uniquely extended extraosseously into the hip joint. Computed tomography scan clearly demonstrated a tumoral lesion of the left femoral neck and a periosteal reaction along the anterior cortex of the femur, distal to the legion. Magnetic resonance imaging showed reactive synovitis with marked joint effusion of the hip and an extensive edema in the proximal femur and the surrounding soft tissues. Aneurysmal bone cysts formation secondary to chondroblastoma was confirmed by histologic examinations of the excised specimens. Complete relief of pain and an improvement in the range of movement of the hip joint was obtained after surgical resection of the tumor.

Background We undertook this study to assess the therapeutic results of superficial soft tissue sarcomas as related to the presence of microscopic invasion, and to identify prognostic factors so as to optimize the therapeutic strategy. Methods From 1995 to 2008, 105 patients who were treated surgically for superficial non-small round cell soft tissue sarcoma were investigated with regard to clinical results and microscopic invasion, and the influence exerted on prognosis was analyzed. We analyzed overall, metastasis-free, and local recurrence-free survival rates and determined the difference in survivorship between with and without fascia invasion. Results The 5-year overall survival rate and 5-year disease-free survival rate were 95.3% and 81.8%. For overall survival, age (P

Purpose To evaluate the efficacy, post-treatment function, toxicity, and complications of carbon ion radiotherapy (RT) for sacral chordoma compared with surgery. Methods and Materials The records of 17 primary sacral chordoma patients treated since 1990 with surgery ( n =10) or carbon ion RT ( n =7) were retrospectively analyzed for disease-specific survival, local recurrence-free survival, complications, and functional outcome. The applied carbon ion dose ranged from 54.0 Gray equivalent (GyE) to 73.6 GyE (median 70.4). Results The mean age at treatment was 55 years for the surgery group and 65 years for the carbon ion RT group. The median duration of follow-up was 76 months for the surgery group and 49 months for the carbon ion RT group. The local recurrence-free survival rate at 5 years was 62.5% for the surgery and 100% for the carbon ion RT group, and the disease-specific survival rate at 5 years was 85.7% and 53.3%, respectively. Urinary-anorectal function worsened in 6 patients (60%) in the surgery group, but it was unchanged in all the patients who had undergone carbon ion RT. Postoperative wound complications requiring reoperation occurred in 3 patients (30%) after surgery and in 1 patient (14%) after carbon ion RT. The functional outcome evaluated using the Musculoskeletal Tumor Society scoring system revealed 55% in the surgery group and 75% in the carbon ion RT group. Of the six factors in this scoring system, the carbon ion RT group had significantly greater scores in emotional acceptance than did the surgery group. Conclusion Carbon ion RT results in a high local control rate and preservation of urinary-anorectal function compared with surgery.

Soft tissue sarcomas are often inappropriately excised without adequate preoperative planning. Inappropriate (unplanned) excisions may adversely affect local recurrence, distant metastasis, patient survival, and /or postoperative function once properly evaluated.We asked whether the clinical and treatment characteristics, survival (overall, local recurrence-free, distant metastasis-free), and functional scores of patients with unplanned excisions differ from those with a planned excision.We retrospectively reviewed 128 patients with planned excisions and 63 patients with unplanned excisions at prereferral hospitals followed by additional reexcisions. We determined whether age, gender, tumor size, depth, histologic grade, operative duration, blood loss, survival, or functional scores differed between the two groups. The minimum followup was 6 months (mean, 55 months; range, 6-275 months).The tumor was larger and its location deeper in the planned excision group. Overall, metastasis-free, and local recurrence-free survival were similar in the two groups: 86%, 71%, and 85% in the planned excision group and 96%, 86%, and 92% in the unplanned excision group, respectively. However, additional soft tissue reconstruction was more often necessary for patients with unplanned excisions. No difference in postoperative function was observed.The data suggest an adequate additional wide excision may improve the local control and survival in patients with an unplanned excision as well as the patients with a planned excision. While patients with unplanned excisions had superficial and smaller tumors, survival and postoperative function were similar to those with planned excisions.

Background Solitary bone only metastasis (SBOM) is a rare condition in which metastasis is limited to a single skeletal lesion originating from a previously treated or controllable primary lesion. The study objective was to evaluate the clinical features and survival regarding this rare condition and to clarify its treatment strategy. Methods A total of 1453 patients with bone metastasis registered in our hospital database were enrolled. To assess the primary and/or metastatic lesion we used plain X-ray images, CT, MRI and FDG-PET scans as well as bone scans. Results Among the patients, only 27 (1.8%) had SBOM. The primary cancers responsible for SBOM were lung in seven patients, breast in five, kidney in four, prostate in two, uterus in two and other types in seven. Treatment of SBOM involved resection in four patients, radiotherapy only in 17, radiotherapy in combination with zoledronate in six and chemotherapy with zoledronate in one. Local recurrence did not develop in the four cases treated with resection. However, in-field recurrence was found in 4 of 22 (18%) patients who underwent radiotherapy. All three patients who received >40 Gy did not develop in-field recurrence. The overall and event free survival rates at 5 years were 63% and 41%, respectively. Conclusions Solitary bone only metastasis should be treated with wide resection or long-course radiotherapy at doses 40–50 Gy to achieve long lasting local tumor control.

A 19-year-old woman sustained a vertical shear type pelvic fracture. Sacroiliac fixation using computed tomography (CT)-guided cannulated screws was performed for a left sacroiliac dislocation fracture, and a satisfactory result was obtained over time. Patients who have posterior instability of the lateral compression or vertical shear type do not obtain adequate stability by fixation of the anterior part alone; and they often have persistent residual pain, necessitating internal fixation of the posterior part later. Advantages of CT-guided sacroiliac screw fixation include precise evaluation of the degree of reduction and absence of nerve and vascular damage during the time the screw is inserted into the sacral body. This procedure is a useful, safe method owing to its minimal invasiveness in patients with unstable pelvic fractures that are reducible by manual manipulation or traction.

A 7-year-old girl was diagnosed with alveolar rhabdomyosarcomas of the right crural region. The patient was initially treated with chemotherapy and surgery with wide surgical margins, with radiotherapy. The tumors relapsed in the popliteal region surrounding the popliteal vessels. The patient received sentinel lymph node biopsy for a recurrent tumor using isosulfan blue dye, with the "sentinel node" being malignant-negative, and a "nonsentinel node" positive. Sentinel lymph node biopsy with conventional blue dye alone might be insufficient to assess lymph node status in patients with recurrent rhabdomyosarcoma previously treated with surgery and/or radiotherapy.

Injection of monoclonal antibody to interleukin-2 (S4B6) into mice depletes regulatory T-cells (Tregs) and exhibits antitumor activities mediated through an autoimmune reaction. In this study, we demonstrate that administration of S4B6 suppresses the murine osteosarcoma cell line, LM8.LM8 osteosarcoma cells were transplanted subcutaneously into C3H mice (n=58). C3H mice were injected intraperitoneally with S4B6 starting at 7 days before LM8 transplantation (pre-S4B6 group), 2 days after transplantation, or 5 days after transplantation. Control group mice were injected with normal rat IgG. Mice were sacrificed and examined 4 weeks later.The number of pulmonary metastatic colonies and the tumor size were significantly reduced in the pre-S4B6 group compared to the control group. In addition, pulmonary metastases were inhibited in mice injected with S4B6 2 days, but not 5 days, after tumor transplantation.S4B6 administration inhibited metastasis even when injected 2 days after LM8 transplantation. Our data suggest that treatment with S4B6 might be suitable in a postoperative clinical setting.

Background: Hyaluronan (HA) plays crucial roles in the tumourigenicity of many types of malignant tumours. 4-Methylumbelliferone (MU) is an inhibitor of HA synthesis. Several studies have shown its inhibitory effects on malignant tumours; however, none have focused on its effects on osteosarcoma. Methods: We investigated the effects of MU on HA accumulation and tumourigenicity of highly metastatic murine osteosarcoma cells (LM8) that have HA-rich cell-associated matrix, and human osteosarcoma cell lines (MG-63 and HOS). Results: In vitro, MU inhibited HA retention, thereby reducing the formation of functional cell-associated matrices, and also inhibited cell proliferation, migration, and invasion. Akt phosphorylation was suppressed by MU (1.0 m). In vivo, although MU showed only a mild inhibitory effect on the growth of the primary tumour, it markedly inhibited (75% reduction) the development of lung metastasis. Hyaluronan retention in the periphery of the primary tumour was markedly suppressed by MU. Conclusion: These findings suggested that MU suppressed HA retention and cell-associated matrix formation in osteosarcoma cells, resulting in a reduction of tumourigenicity, including lung metastasis. 4-Methylumbelliferone is a promising therapeutic agent targeting both primary tumours and distant metastasis of osteosarcoma, possibly via suppression of HA retention.

We undertook this study to assess the therapeutic results of superficial soft tissue sarcomas as related to the presence of microscopic invasion, and to identify prognostic factors so as to optimize the therapeutic strategy.From 1995 to 2008, 105 patients who were treated surgically for superficial non-small round cell soft tissue sarcoma were investigated with regard to clinical results and microscopic invasion, and the influence exerted on prognosis was analyzed. We analyzed overall, metastasis-free, and local recurrence-free survival rates and determined the difference in survivorship between with and without fascia invasion.The 5-year overall survival rate and 5-year disease-free survival rate were 95.3% and 81.8%. For overall survival, age (P 0.05), grade (P 0.05), tumor size (P 0.05), and fascial invasion (P 0.0001) were significant unfavorable prognostic factors, while for metastasis-free survival, grade (P 0.01) and fascial invasion (P 0.001) were significant unfavorable prognostic factors. For local recurrence-free survival, fascial invasion alone (P 0.01) was a significant unfavorable prognostic factor.Fascial invasion on pathological examination of resected specimens was identified as a significant unfavorable prognostic factor. Selecting the postoperative adjuvant therapy based on a detailed evaluation of any fascial invasion is an important part of the therapeutic strategy.

Hyaluronan (HA) oligosaccharides were reported to have suppressive effects on various malignant tumors via disruption of receptor HA interactions. However, no studies have focused on the effects of HA oligosaccharides on bone metastasis of breast cancer. In this study, we clarified the effective size of HA oligosaccharides required to inhibit cell growth in the highly invasive breast cancer cell line, MDA-MB-231 cells. Based on the results of cell growth assay, we subsequently analyzed the effects of HA tetrasaccharides, HA decasaccharides, and high molecular weight HA on the other breast cancer cell behaviors in vitro and breast cancer bone metastasis in vivo. HA decasaccharides significantly inhibited cell growth, motility, and invasion, whereas tetrasaccharides did not. HAS2 mRNA expression was altered after the treatment with both tetrasaccharides and decasaccharides. Phosphorylation of Akt was suppressed after 1 h treatment with HA decasaccharides, and the effect was partially reversed by anti-CD44 monoclonal antibody. In vivo, local application of HA decasaccharides inhibited the expansion of osteolytic lesions in tibia on soft X-rays using mouse bone metastasis model of breast cancer. Histological analysis revealed HA accumulation in bone metastatic lesions was perturbed by decasaccharides. These results suggest that HA oligosaccharides suppressed progression of bone metastasis in breast cancer via interruption of endogenous HA–CD44 interaction, and as such, can be a novel therapeutic candidate to limit bone metastasis of breast cancer. © 2011 Orthopaedic Research Society. © 2011 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 30:662–672, 2012

Versican, a large chondroitin sulfate proteoglycan that binds hyaluronan and is composed of large extracellular matrix aggregates, has been shown to correlate with tumor progression. No studies have examined the roles of versican in chondrosarcoma nor compared them to those of aggrecan. In clinical specimens of human chondromatous tumors, versican expression was significantly increased in malignant tumors, moreover, as the tumor grade increased. To clarify the roles of versican in chondrosarcoma, versican splicing variant 1, variant 3 or only GFP was stably transfected to Swarm rat chondrosarcoma cells with Trap-In System. Forced expression of versican V1 isoform in Swarm rat chondrosarcoma cells induced a marked increase of cell-associated matrix compared to V3-, GFP- transfected or RCS cells. Versican was immunolocalized in a fashion similar to that of hyaluronan and more diffusively than aggrecan. Anchor-dependent and -independent growth was not affected by versican isoform expression, whereas cell motility and migration were significantly enhanced by V1 isoform transfection. Tumors formed in vivo with V1-transfected cells exhibited more myxomatous area and included more spindle shaped cells. These results support the concept that versican has the capacity to form more extensive cell-associated matrix than aggrecan, and the prominent matrix formation alters the cell behavior of chondrosarcoma more aggressively. These observations suggest that versican expression may serve as a marker of tumor grade determination in chondrosarcoma and possibly help to decide on therapeutic targets in higher grades of chondrosarcoma.

The healing process of structural pasteurized autogenous bone graft has not been studied in detail. The purpose of this investigation was to assess the reparative process of pasteurized bone graft histologically, and clarify the factors influencing the outcome. From among 51 cases using pasteurized autogenous bone graft since 1992, 10 specimens were retrieved after lower extremity reconstruction of tibia or femur with or without simultaneous fibula flap, and subjected to the analysis. Regeneration of the grafted bone was assessed as the ratio of the number of viable cells to that of whole cells. Pasteurized bone combined with a vascularized fibula showed markedly better repair. Long duration from implantation to retrieval was associated with a better reparative process with vascularized fibula (P = 0.03), whereas other factors had no significant impact. This study demonstrated that pasteurized autogenous bone graft remained structurally stable for many years, although facilitators such as the combined use of a vascularized fibula are required to promote regeneration of the graft.

Angiogenesis is involved in the growth and metastasis of most solid tumors. Several reports have demonstrated that angiotensin II stimulates growth and migration of certain cancer cell lines and induces angiogenesis through up-regulation of vascular endothelial growth factor. This study examined whether an angiotensin II type 1 receptor (AT1R) antagonist (CV11974) inhibits osteosarcoma progression and distant metastasis.Osteosarcoma (LM8) was transplanted into subcutaneous dorsal tissue of C3H mice. The mice were administered CV11974 daily by intraperitoneal injections at 0.1 mg/kg, 1 mg/kg, or 10 mg/kg, or saline for 28 days.Subcutaneous tumor size was smaller in the CV11974 treatment groups than in the control group. Lung and liver metastases were significantly reduced in the CV11974 treatment groups when compared with the control group.CV11974 is widely used to treat hypertension clinically and therefore may be a novel antiangiogenic therapy for osteosarcoma through blocking AT1R-mediated signaling.

Hyaluronan (HA) has been shown to play crucial roles in the tumorigenicity of malignant tumors. Previous studies demonstrated that inhibition of HA suppressed the tumorigenicity of various malignant tumors including breast cancer. 4-methylumbelliferone (MU) has been reported to inhibit HA synthesis in several cell types. However, few studies have focused on the effects of HA inhibition in breast cancer cells by MU, nor the effects on bone metastasis. We hypothesized that MU would suppress the progression of bone metastasis via inhibition of HA synthesis. Here, we investigated the effects of MU on HA expression in MDA-MB-231 breast cancer cell line in addition to their tumorigenicity in vitro and in vivo. HAS2 mRNA expression was downregulated after 6 and 24 hr treatment with MU. Quantitative analysis of HA revealed that MU significantly inhibited the intracellular and cell surface HA. MU significantly inhibited cell growth and induced apoptosis as determined by cell proliferation and TUNEL assays, respectively. Phosphorylation of Akt was suppressed after 12 and 24 hr treatment with MU. MU treatment also inhibited cell motility as well as cell invasiveness. MU also inhibited cell growth and motility in murine fibroblast cell line NIH3T3. In vivo, administration of MU inhibited the expansion of osteolytic lesions on soft X-rays in mouse breast cancer xenograft models. HA accumulation in bone metastatic lesions was perturbed peripherally. These data suggest that MU might be a therapeutic candidate for bone metastasis of breast cancer via suppression of HA synthesis and accumulation.

Many studies have identified factors prognostic for soft tissue sarcomas of local recurrence, and distant metastasis. Several studies demonstrated that some subsets of patients could be safely treated by surgery alone, with acceptable rates of local recurrence. The aim of this study was to better clarify the necessity for adjuvant therapy and the width of the resected margin, by investigating the clinicopathological results of T1 (≤5 cm) soft tissue sarcomas.A retrospective review was conducted in 96 adult patients treated for nonmetastatic AJCC T1 primary non-small round cell soft tissue sarcomas in our institution from 1995 to 2008. There were 49 men and 47 women ranging in age from 18 to 85 years (mean 51), and the observation period was 6-159 months (mean 52). The site of origin was the upper extremity in 21 cases, the lower extremity in 45, and the trunk in 30. Forty-four cases had high-grade malignant tumors, and 52 had low-grade malignant ones. Tumor size ranged from 0.7 to 5.0 cm (median size, 3.5 cm). Thirty-nine cases (41%) had previously undergone unplanned excision elsewhere.Eighty-nine (93%) of the patients were continuously free of disease, four were alive and currently free of disease, one was alive with metastasis, and two had died. The event-free survival rate at 5 years was 93.3%. The overall survival rate at 5 years was 94.1%. In 23 of the 45 cases with unplanned excisions (51%) residual tumor was found on histological examination. After definitive surgery, 92 patients (96%) had R0 margins. Four patients (4%) had R1 margins and were treated with postoperative radiotherapy. Forty-five of 51 cases after planned biopsies (88%) showed infiltrative growth microscopically.Tumor size was found to have a major impact on the prognosis of soft tissue sarcomas, emphasizing the importance of early detection and early treatment of these tumors. Most patients suffering from T1 soft tissue sarcomas might be able to avoid adjuvant therapies including radiotherapy and chemotherapy. To achieve good local control with surgery alone, an adequate surgical margin must be achieved even for small lesions.

The objective of this study was to identify the MRI criteria that best differentiate malignant peripheral nerve sheath tumors from benign neurofibromas.We retrospectively analyzed MR images obtained for 41 histologically diagnosed cases of malignant peripheral nerve sheath tumor and 20 cases of neurofibroma that had been treated at four tertiary institutions. Twenty of the patients with malignant peripheral nerve sheath tumors and 14 patients with neurofibromas developed the disease in association with neurofibromatosis 1. The MR images were evaluated with regard to tumor size, signal intensity, heterogeneity of T1- and T2-weighted MR images, enhancement pattern, definition of margins, presence of perilesional edemalike zone, and presence of intratumoral cystic lesions.Significant differences between malignant peripheral nerve sheath tumors and neurofibromas were noted for the largest dimension of the mass, peripheral enhancement pattern, perilesional edemalike zone, and intratumoral cystic lesion. In cases associated with neurofibromatosis 1, heterogenicity on T1-weighted images was also significant in differentiating neurofibroma from malignant peripheral nerve sheath tumor. The presence of two or more of the four features suggestive of malignancy indicated malignant peripheral nerve sheath tumor with a sensitivity of 61% and a specificity of 90%.The MR features described in this study are useful for distinguishing malignant peripheral nerve sheath tumors from neurofibromas. If a tumor has two or more of the four statistically significant features, it can be considered to be highly suspicious of malignancy and should be subjected to a biopsy for early diagnosis.

Nodular fasciitis rarely arises in the hand. We describe 4 cases that were histologically diagnosed as nodular fasciitis on biopsy specimens arising in the hands. The masses of 2 patients were excised due to rapid growth. Both of these patients had no recurrence. The other 2 patients were followed without surgical excision, and the masses partially regressed without functional impairment.

It is difficult to differentiate some malignant peripheral nerve sheath tumors (MPNST) from benign peripheral nerve sheath tumors (BPNST) histologically, and to predict the clinical outcome of patients with MPNST. In this study, the expression of VEGF and MVD were evaluated immunohistochemically in 22 cases of MPNST, 14 of neurofibroma and 19 of schwannoma and correlation of the staining grade of VEGF or MVD and the various clinical factors were analyzed, and statistically evaluated. Levels of VEGF mRNA expression were also determined with real-time RT-PCR. Statistically higher positive staining for VEGF was observed in MPNST compared to neurofibroma (P = 0.004) and schwannoma (P < 0.001). Even low grade MPNST showed higher VEGF positive staining than neurofibroma. Moreover, high VEGF expression statistically correlated with the poor prognosis of the patients with MPNST (P = 0.015). Although MVD in MPNST was significantly higher than that in neurofibroma (P = 0.038) and schwannoma (P < 0.001), MVD could not predict the prognosis of the patients with MPNST. Although VEGF mRNA expression tended to be higher in MPNST compared to neurofibroma, the difference was not significant. Levels of VEGF protein expression serve as a novel diagnostic and prognostic tools for peripheral nerve sheath tumors.

We here describe a case of multiple pyomyositis in a 62-year-old man who had systemic chemotherapy for recurrent lung cancer. His initial symptoms consisted of fever and general fatigue, followed by progressive pain and swelling in his extremities, which mimicked deep venous thrombosis along with bacterial infection. He was admitted to the hospital for intravenous administration of antibiotics. MRI appeared very useful to find the intramuscular fluid collections with circumferential inflammatory changes, which confirmed diagnosis of the multiple pyomyositis. Surgical drainage as well as intravenous administration of antibiotics worked very well and improved clinical symptoms in a few weeks after the treatments. He could resume normal activities with minimum functional impairments in the extremities. Pyomyositis should be kept in mind as one of the adverse effects after chemotherapy for malignant tumors.

Human retinoblastoma (Rb) protein, immunopurified from an extract of recombinant baculovirus infected cells, stimulated 10-100-fold the activity of DNA polymerase alpha from calf thymus or human HeLa cells. Purified Rb protein is composed of two electrophoretically distinguishable forms, i.e., partially phosphorylated and under-phosphorylated forms. Dephosphorylation of Rb protein by protein phosphatase 2A largely diminished its stimulatory effect. On the other hand, a hyperphosphorylated Rb protein, obtained from insect cells overexpressing Rb protein, cyclin E and cyclin-dependent kinase 2 simultaneously, stimulated DNA polymerase alpha more strongly than the singly-expressed Rb protein. These results indicate that the phosphorylation is crucial for the stimulation. Rb protein isolated from human Burkitt lymphoma Raji cells also stimulated DNA polymerase alpha. In contrast, Rb protein did not affect eukaryotic DNA primase or Klenow fragment of Escherichia coli DNA polymerase I. By immunoprecipitation using anti-DNA polymerase alpha antibody, Rb protein in nuclear extract of Raji cells was co-precipitated with DNA polymerase alpha. This result indicates that DNA polymerase alpha exists as a complex containing phosphorylated Rb protein in cells. DNA polymerase alpha specifically bound to a purified Rb protein-immobilized Sepharose column. Rb protein also bound to DNA polymerase alpha trapped to anti-DNA polymerase alpha antibody-Sepharose column, suggesting the direct association of these two proteins. These observations suggest a new function of phosphorylated Rb protein in the regulation of DNA replication.