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.

Prediction of the future leg length after rotationplasty in a 3-year-old boy with extraskeletal Ewing sarcoma and long follow-up until skeletal maturity: a case report.

Rotationplasty is a useful option for limb salvage surgery in pediatric patients with malignant bone and soft tissue tumors. However, bone growth after rotationplasty remains poorly characterized. We present a case of a 3-year-old boy with extraskeletal Ewing sarcoma who underwent multidrug chemotherapy (vincristine, doxorubicin, ifosfamide and etoposide), wide resection and functional reconstruction with rotationplasty. No radiotherapy was administered during the treatment course and the patient has been followed up for 16 years after rotationplasty. Leg length at skeletal maturity was predicted using postoperative radiograph measurements of the affected leg at the age of 4 years. Two conventional prediction methods, the multiplier and straight-line graph methods were used for prediction. The predicted leg length was compared with the actual leg length to assess bone growth after rotationplasty. Immediately after surgery, the lengths of the affected lower leg, femur and tibia were 32.5, 15.0 and 17.6 cm, respectively, and the predicted leg length of the affected leg at skeletal maturity using the multiplier and straight-line graph methods was 44.6 and 44.2 cm, respectively. However, the actual length of the affected leg at skeletal maturity was 49.8 cm, and the gap between actual and predicted lengths was more than 5 cm. In conclusion, the affected leg after rotationplasty showed more than expected bone overgrowth compared with the predictions of the conventional methods.

An analysis of tumor-related skin temperature differences in malignant soft-tissue tumors.

BACKGROUND: Soft tissue tumors are often accompanied with elevated skin temperature; however, studies concerning the relationship between soft-tissue tumors and skin temperature elevation are scarce. We aimed to evaluate the clinical significance of skin temperature elevation in soft-tissue tumors and identify factors related to skin temperature elevation. PATIENTS AND METHODS: This study comprised 118 patients at our hospital with soft-tissue tumors, excluding lipomatous tumors, whose pathological diagnosis was surgically confirmed between February 2017 and March 2021. Sixty-one and 57 patients had been diagnosed with benign lesions and malignant tumors, respectively (men, 64; women, 54; median age, 61 [range, 20-92] years). The relationship between skin temperature, monitored using a thermography camera, and the presence of soft-tissue malignancy was investigated. We reviewed clinical data to identify factors related to elevated skin temperature. RESULTS: Temperature differences ≥ 0.2 °C compared to the unaffected side were significantly associated with the presence of malignant tumors (p < 0.001). Logistic regression analysis indicated that intertumoral blood supply was associated with elevated skin temperature (OR 3.22, 95% CI 2.03-5.13; p < 0.001). CONCLUSIONS: Elevated skin temperature, influenced by intertumoral blood supply, may be an important adjunct to physical findings when diagnosing malignant soft-tissue tumors. CLINICAL RELEVANCE: Intertumoral blood supply influenced elevated skin temperature in malignant soft-tissue tumors. A skin temperature difference ≥ 0.2 °C compared to the unaffected side can help differentiate between benign and malignant tumors. Skin temperature differences may help in diagnosing malignant soft-tissue tumors.

Japan Society of Clinical Oncology Clinical Practice Guidelines 2017 for fertility preservation in childhood, adolescent, and young adult cancer patients: part 2.

The Japan Society of Clinical Oncology (JSCO) published the "JSCO Clinical Practice Guidelines 2017 for Fertility Preservation in Childhood, Adolescent, and Young Adult Cancer Patients" in 2017. This was the first guideline in cancer reproductive medicine in Japan. In the field of cancer reproductive medicine, close cooperation between an oncologist and a physician for reproductive medicine is important from before treatment initiation until long after treatment. The guideline takes into consideration disease specificity and provides opinions from the perspective of oncologists and specialists in reproductive medicine that are in line with the current state of the Japanese medical system. It is intended to serve as a reference for medical staff in both fields regarding the availability of fertility preservation therapy before the start of cancer treatment. Appropriate use of this guideline makes it easier to determine whether fertility preservation therapy is feasible and, ultimately, to improve survivorship in childhood, adolescent, and young adult cancer patients. In this article (Part 2), we describe details by organ/system and also for pediatric cancer.

Japan Society of Clinical Oncology Clinical Practice Guidelines 2017 for fertility preservation in childhood, adolescent, and young adult cancer patients: part 1.

In 2017, the Japan Society of Clinical Oncology (JSCO) published the JSCO Clinical Practice Guidelines 2017 for Fertility Preservation in Childhood, Adolescent, and Young Adult Cancer Patients. These were the first Japanese guidelines to address issues of oncofertility. In this field of medicine, sustained close cooperation between oncologists and reproductive specialists is essential from the diagnosis of cancer until many years after completion of cancer treatment. These JSCO guidelines were intended to guide multidisciplinary medical staff in considering the availability of fertility preservation options and to help them decide whether to provide fertility preservation to childhood, adolescent, and young adult cancer patients before treatment starts, with the ultimate goal of improving patient survivorship. The guidelines are presented as Parts 1 and 2. This article (Part 1) summarizes the goals of the guidelines and the methods used to develop them and provides an overview of fertility preservation across all oncology areas. It includes general remarks on the basic concepts surrounding fertility preservation and explanations of the impacts of cancer treatment on gonadal function by sex and treatment modality and of the options for protecting/preserving gonadal function and makes recommendations based on 4 clinical questions. Part 2 of these guidelines provides specific recommendations on fertility preservation in 8 types of cancer (gynecologic, breast, urologic, pediatric, hematologic, bone and soft tissue, brain, and digestive).

Giant cell tumor of bone - Analysis of 213 cases involving extra-craniofacial bones.

We elucidated clinicopathological characteristics of giant cell tumor of bone (GCTB) in Japan, and significant clinicopathological factors for predicting local recurrence. Clinicopathological profiles of 213 patients with GCTB (100 male, 113 female) involving extra-craniofacial bones were retrieved. Pathological slides obtained at the initial surgery were reviewed. Fourteen pathological and five clinical features were statistically analyzed to disclose prognostic significance. Patient age ranged from 12-80 years (Average 38.7). Long bones were most frequently affected (86.4%), especially around the knee (62.9%). Histological features are basically similar to those previously reported. Within a follow-up period (24-316 months, average 106.1 months), the local recurrence rate is 29.1%. Metastasis has occurred in 9 patients. Cox regression analysis of representative clinicopathological features shows that younger age, higher mitotic count, smaller zones of stromal hemorrhage, considerable vascular invasion and absence of ischemic necrosis are significant predictors for local recurrence. Initial operative method (curettage) is a significant risk factor in univariate analysis but not by multivariate analysis (P = 0.053). Denosumab administration increases risk but not significantly (P = 0.053). Histone 3.3 G34W immunopositivity is not significant for predicting local recurrence.

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.

Randomized placebo-controlled double-blind phase II study of zaltoprofen for patients with diffuse-type and unresectable localized tenosynovial giant cell tumors: a study protocol.

BACKGROUND: A tenosynovial giant cell tumor (TGCT) is a locally aggressive benign neoplasm arising from intra- or extra-articular tissue. Diffuse TGCT (D-TGCT) most commonly develops in the knee, followed by the hip, ankle, elbow, and shoulder. Surgical removal is the only effective treatment option for the patients. However, a local recurrence rate as high as 47% has been reported. Recently, we revealed that zaltoprofen, a nonsteroidal anti-inflammatory drug possessing the ability to activate peroxisome proliferator-activated receptor gamma (PPARγ), can inhibit the proliferation of TGCT stromal cells via PPARγ. PPARγ is a ligand-activated transcription factor that belongs to the nuclear hormone receptor superfamily. It plays an important role in the differentiation of adipocytes from precursor cells and exhibits antitumorigenic effects on certain malignancies. Therefore, we are conducting this investigator-initiated clinical trial to evaluate whether zaltoprofen is safe and effective for patients with D-TGCT or unresectable localized TGCT (L-TGCT). METHODS: This study is a randomized, placebo-controlled, double-blind, multicenter trial to evaluate the safety and efficacy of zaltoprofen for patients with D-TGCT or L-TGCT. For the treatment group, zaltoprofen 480 mg/day will be administered for 48 weeks; the placebo group will receive similar dosages without zaltoprofen. Twenty participants in each group are needed in this trial (40 participants total). The primary outcome is the progression-free rate at 48 weeks after treatment administration. "Progression" is defined as any serious events (1. Repetitive joint swelling due to hemorrhage, 2. Joint range of motion limitation, 3. Invasion of adjacent cartilage or bone, 4. Severe joint space narrowing, 5. Increase in tumor size) requiring surgical interventions. We hypothesize that the zaltoprofen group will have a higher progression-free rate compared to that of the placebo group at 48 weeks. DISCUSSION: This is the first study to evaluate the efficacy of zaltoprofen in patients with D-TGCT or unresectable L-TGCT. We believe that the results of this trial will validate a novel treatment option, zaltoprofen, to stabilize disease progression for TGCT patients. TRIAL REGISTRATION: University Hospital Medical Information Network (UMIN) Clinical Trials Registry ( UMIN000025901 ) registered on 4/01/2017.

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.

Promising effects of eribulin for cystic lung metastases of epithelioid sarcoma: a case report.

Epithelioid sarcoma (ES) is a rare and aggressive type of soft tissue sarcoma with resistance to systemic chemotherapy. Therefore, new treatment options are required for patients with advanced ES. Eribulin is a novel potential treatment option for patients with inoperative sarcoma. We herein report a case of a 27-year-old Japanese man with cystic lung metastases from an ES in the left forearm, resulting in long-term stable disease. A solid, metastatic sarcomatous nodule appeared in the right lung, as shown by computed tomography, within the first 2 months after surgery. After the lung metastasis was detected, he underwent a total of 37 cycles of chemotherapy in six regimens. However, multiple cystic lung metastases had progressed in segments S6 and S9/10; hence, eribulin treatment was initiated. After two courses of eribulin, the excess fluid density material in the cystic metastases was completely absorbed, and an additional four courses of treatment resulted in shrinkage of the cystic metastases. These effects lasted for 13 months without severe adverse effects. Cystic lung metastases are an extremely rare consequence of soft tissue sarcoma, and eribulin is one of the most promising options for the treatment of advanced ES.

Chondroblastoma of extra-craniofacial bones: Clinicopathological analyses of 103 cases.

We elucidated clinicopathological characteristics of chondroblastoma (CB) in Japan, and reliable clinicopathologic parameters predicting local recurrence and/or metastasis. Clinicopathological profiles of 103 CB (80 male, 23 female) in extra-craniofacial bones were retrieved. Numerical scoring of nine pathological and five radiological features was statistically analyzed to determine prognostic significance. Age ranged 8-61 years (average 19.6 years). Frequently involved sites were femur, tibia, calcaneus, patella and humerus. Radiologically, tumors were 2-80 mm (average 31.1 mm) in size. Marginal sclerosis and calcification were common. Histologically, pink cartilage, mitoses, and chicken-wire calcification were often seen. Within a follow-up period [2-260 months (average 53.5 months)], the local recurrence rate was 15.5%. No patient had metastasis. Recurrence was most frequently observed at the femur. By log-rank analysis, only cyst formation in images was significant for predicting recurrence free survival (RFS). By Cox hazard analysis with representative clinico-radiological and pathological features, only age (≥16 years) and cyst formation were significant predictors for RFS. Pathological features were not significant in both uni- and multivariate analyses.

Clinical features of soft tissue sarcoma presenting intra-tumour haematoma: case series and review of the literature.

INTRODUCTION: Intra-tumour haematoma is an uncommon clinical presentation in malignant soft tissue tumours. This study aimed to highlight the clinical features of patients with soft tissue sarcomas with intra-tumour haematoma. METHODS: The patient group was composed of eight men and one woman aged between 29 and 83 years (mean 44.0 ± 20.8). The average follow-up was 29.8 months. Clinical information, including clinical features, radiological information and treatment course, was retrospectively investigated. RESULTS: Tumours were predominantly located in the chest wall and thigh, and average diameter was 10.3 cm. Six patients underwent needle biopsy with ultrasound sonography, and three underwent an open biopsy. Histological diagnoses indicated that all tumours were high grade, three of which were undifferentiated pleomorphic sarcomas, three synovial sarcomas, two pleomorphic liposarcomas, one a leiomyosarcoma and one a malignant peripheral nerve sheath tumour. The median diagnostic delay time was 3.0 months. Magnetic resonance imaging (MRI) indicated a haematoma area <25 % in three, 25-50 % in four and 50 % two. A wide resection was performed in eight patients, and radiotherapy was administered to one patient for the initial local treatment of a primary tumour. Local recurrence was detected in four patients, whilst five developed lung metastases. The five-year survival rate was 57.1 % and median survival 34.0 months. CONCLUSIONS: Soft tissue sarcomas with intra-tumour haematoma presented with locally aggressive and highly metastatic behavior, consistent with high-grade tumours.

Primary central chondrosarcoma of long bone, limb girdle and trunk: Analysis of 174 cases by numerical scoring on histology.

The aims of this study were: (i) to elucidate clinicopathological characteristics of pcCHS of long bones (L), limb girdles (LG) and trunk (T) in Japan; (ii) to investigate predictive pathological findings for outcome of pcCHS of L, LG and T, objectively; and (iii) to elucidate a discrepancy of grade between biopsy and resected specimens. Clinicopathological profiles of 174 pcCHS (79 male, 95 female), of L, LG, and T were retrieved. For each case, a numerical score was given to 18 pathological findings. The average age was 50.5 years (15-80 years). Frequently involved sites were femur, humerus, pelvis and rib. The 5-year and 10-year disease-specific survival (DSS) rates [follow-up: 1-258 months (average 65.5)] were 87.0% and 80.4%, respectively. By Cox hazards analysis on pathological findings, age, sex and location, histologically higher grade and older age were unfavorable predictors, and calcification was a favorable predictor in DSS. The histological grade of resected specimen was higher than that of biopsy in 37.7% (26/69 cases). In conclusion, higher histological grade and older age were predictors for poor, but calcification was for good prognosis. Because there was a discrepancy in grade between biopsy and resected specimens, comprehensive evaluation is necessary before definitive operation for pcCHS.

Knee reconstruction with endoprosthesis after extra-articular and intra-articular resection of osteosarcoma.

OBJECTIVE: Extra-articular resection is necessary to obtain a wide margin for primary osteosarcomas invading the knee joint, and the limb is often reconstructed using a prosthesis. Here, outcomes of extra-articular and intra-articular procedures were compared. METHODS: Between 1999 and 2012, 14 patients with osteosarcoma underwent extra-articular excision (n = 6; ages 23-65 years; mean follow-up 82.8 months) or intra-articular excision (n = 8; ages 8-58 years; mean follow-up 96.4 months). In the extra-articular group, there was one Enneking Stage IIA case and five Enneking Stage IIB cases. No local recurrences were noted in either group. RESULTS: Patient outcomes were as follows (extra-articular cases vs. intra-articular cases): continuous disease-free (2 vs. 7), alive with disease (2 vs. 0) and death from disease (1 vs. 1). Average Musculoskeletal Tumor Society functional scores were 69.4% (range 63.3-83.3%) and 88.3% (range 70.0-96.7%) in the extra-articular and intra-articular groups, respectively, constituting a significant difference (P < 0.05). The 5-year oncological overall survival exceeded 80% in both groups. Amputation was necessary for one patient in the extra-articular group. The 5-year event-free prosthesis survival rates in the extra-articular and intra-articular groups were 33.3 and 75.0%, respectively (P < 0.05). CONCLUSION: The extra-articular excision group developed more complications than the intra-articular excision group, as a result of extensive bone and muscle excision. The limb survival rates were similar in both groups. Our results suggest that extra-articular resection was a necessary and clinically acceptable procedure.

Diagnosis of osteosarcoma in a patient previously treated for Ewing sarcoma.

Primary malignant bone tumors, whether Ewing sarcoma or osteosarcoma, are a rare type of tumor. The sequential occurrence of two bone sarcomas, Ewing sarcoma and high-grade osteosarcoma, in the same patient at two different locations is an exceptionally rare phenomenon. We present the case of a 13-year-old girl who presented with a high-grade osteoblastic osteosarcoma of the distal femur, 7 years after treatment for Ewing sarcoma of the left pelvis. She did not receive radiation therapy. Following the recent developing multidisciplinary therapy, long-term follow-up for monitoring latent treatment-related adverse effects may be necessary for survivors of primary malignant bone tumors.

Prognostic factors for patients with solitary bone metastasis.

BACKGROUND: The term 'solitary bone metastasis' is defined in the present study as a single bone metastasis originating from a primary cancer without visceral organ metastasis. We assessed the survival rates and prognostic factors in 42 patients with solitary bone metastasis, and discussed the impact of different surgical strategies on survival. METHODS: We retrospectively analyzed data from 42 patients (25 male, 17 female) who underwent treatment for solitary bone metastasis at a single institution. The median age of the patients was 64.5 years (range 41-82 years). The patients were followed for an average period of 21.2 months (range 0.4-127.3 months). Their clinical records were retrospectively reviewed. Factors influencing survival were determined using univariate and multivariate analyses; particular attention was paid to the orthopedic surgery used for solitary bone metastasis. RESULTS: The 1-year survival rate was 76.5%, and the median survival period was 30.0 months. The presence of primary cancer and poor performance status were identified as independent prognostic factors using Cox regression multivariate analysis. Tumor resection and surgical margin were not significantly related to patient survival. CONCLUSIONS: The results of this analysis indicated that the prognosis for patients with solitary bone metastasis depended on the presence of primary cancer and on poor performance status.