Significance of radiation therapy in the myxoid round-cell liposarcoma treatment regimen.

BACKGROUND AND PURPOSE: Because myxoid liposarcomas are more radiosensitive than other soft tissue sarcomas, there have been several reports of 50 Gy preoperative radiation therapy combined with surgery, but the wound complication rate is reportedly high. We have performed preoperative irradiation at a reduced dose of 40 Gy and definitive radiation therapy for unresectable cases. This study aimed to report the tumor reduction rate and oncological results with a reduced dose of preoperative irradiation and the outcome of definitive irradiation for unresectable cases. MATERIALS AND METHODS: Forty-one patients with myxoid liposarcoma treated in our institution between 2002 and 2021 were included. We examined the tumor volume shrinkage rate with preoperative radiation, compared complications and oncological outcomes between preoperative radiation and surgery-only cases, and investigated the prognosis and tumor shrinkage of definitive radiation cases. RESULTS: The total dose irradiated was 40 Gy except in two cases. The mean tumor volume reduction rate was 52.0%. A decreased dose of preoperative radiation did not worsen clinical outcomes with fewer complications. The total dose of definitive radiation was approximately 60 Gy. The mean tumor volume reduction rate was 55.0%. The tumor shrinkage maintenance rate was 100% in a median follow-up period of 50.5 months. CONCLUSION: Preoperative radiation therapy for myxoid liposarcoma near vital organs is a good approach because even with a reduced dose of 40 Gy, significant tumor reduction and excellent results were achieved. Definitive radiation therapy is the recommended treatment for older patients with serious comorbidities or inoperable patients.

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.

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.

A bone replacement-type calcium phosphate cement that becomes more porous in vivo by incorporating a degradable polymer.

This study investigated whether mixing low viscosity alginic acid with calcium phosphate cement (CPC) causes interconnected porosity in the CPC and enhances bone replacement by improving the biological interactions. Furthermore, we hypothesized that low viscosity alginic acid would shorten the setting time of CPC and improve its strength. CPC samples were prepared with 0, 5, 10, and 20% low viscosity alginic acid. After immersion in acetate buffer, possible porosification in CPC was monitored in vitro using scanning electron microscopy (SEM), and the setting times and compressive strengths were measured. In vivo study was conducted by placing CPC in a hole created on the femur of New Zealand white rabbit. Microcomputed tomography and histological examination were performed 6 weeks after implantation. SEM images confirmed that alginic acid enhanced the porosity of CPC compared to the control, and the setting time and compressive strength also improved. When incorporating a maximum amount of alginic acid, the new bone mass was significantly higher than the control group (P = 0.0153). These biological responses are promising for the translation of these biomaterials and their commercialization for clinic applications.

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.

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.

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.

[A case of hepatic sarcoidosis presenting with cirrhotic symptoms].

A man in 40s with skin sarcoidosis presented with signs and symptoms of liver injury and thrombocytopenia. Enhanced computed tomography and magnetic resonance imaging revealed cholecystolithiasis, hepatic deformation, and giant splenomegaly. Gastrointestinal endoscopy showed esophageal varices. Cholecystectomy, splenectomy, and wedge biopsy of the liver were performed. Histopathology of the liver revealed many granulomas and severe periportal fibrosis without lobular reconstruction. These findings were compatible with hepatic sarcoidosis, but not liver cirrhosis. Here we report a rare case of hepatic sarcoidosis presenting with cirrhotic symptoms.

Fracture healing on non-union fracture model promoted by non-thermal atmospheric-pressure plasma.

Non-thermal atmospheric-pressure plasma (NTAPP) is attracting widespread interest for use in medical applications. The tissue repair capacity of NTAPP has been reported in various fields; however, little is known about its effect on fracture healing. Non-union or delayed union after a fracture is a clinical challenge. In this study, we aimed to investigate how NTAPP irradiation promotes fracture healing in a non-union fracture model and its underlying mechanism, in vitro and in vivo. For the in vivo study, we created normal and non-union fracture models in LEW/SsNSlc rats to investigate the effects of NTAPP. To create a fracture, a transverse osteotomy was performed in the middle of the femoral shaft. To induce the non-union fracture model, the periosteum surrounding the fracture site was cauterized after a normal fracture model was created. The normal fracture model showed no significant difference in bone healing between the control and NTAPP-treated groups. The non-union fracture model demonstrated that the NTAPP-treated group showed consistent improvement in fracture healing. Histological and biomechanical assessments confirmed the fracture healing. The in vitro study using pre-osteoblastic MC3T3-E1 cells demonstrated that NTAPP irradiation under specific conditions did not reduce cell proliferation but did enhance osteoblastic differentiation. Overall, these results suggest that NTAPP is a novel approach to the treatment of bone fractures.

In vivo study on the repair of rat Achilles tendon injury treated with non-thermal atmospheric-pressure helium microplasma jet.

Non-thermal atmospheric-pressure plasma (NTAPP) has been widely studied for clinical applications, e.g., disinfection, wound healing, cancer therapy, hemostasis, and bone regeneration. It is being revealed that the physical and chemical actions of plasma have enabled these clinical applications. Based on our previous report regarding plasma-stimulated bone regeneration, this study focused on Achilles tendon repair by NTAPP. This is the first study to reveal that exposure to NTAPP can accelerate Achilles tendon repair using a well-established Achilles tendon injury rat model. Histological evaluation using the Stoll's and histological scores showed a significant improvement at 2 and 4 weeks, with type I collagen content being substantial at the early time point of 2 weeks post-surgery. Notably, the replacement of type III collagen with type I collagen occurred more frequently in the plasma-treated groups at the early stage of repair. Tensile strength test results showed that the maximum breaking strength in the plasma-treated group at two weeks was significantly higher than that in the untreated group. Overall, our results indicate that a single event of NTAPP treatment during the surgery can contribute to an early recovery of an injured tendon.

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.

Perivascular epithelioid cell tumors (PEComas) of the bone and soft tissue: a Japanese Musculoskeletal Oncology Group (JMOG) multi-institutional study.

PURPOSE: Perivascular epithelioid cell tumors (PEComas) of the bone and soft tissues are rare mesenchymal neoplasms, some of which are malignant. However, their clinical and pathological characteristics remain unclear. This study was performed to investigate the clinical and pathological characteristics of PEComas in bone and soft tissues by leveraging information from the Japanese Musculoskeletal Oncology Group. METHODS: Nine patients, including four male and five female patients with a median age of 50 years, were retrospectively reviewed. PEComas of the visceral organs, including the uterus and retroperitoneum, were excluded. RESULTS: Eight tumors arose in the soft tissue and one in the bone, with a mean size of 8.8 cm. Four patients showed local recurrence or distant metastasis. The 1-year survival rate was 78%. Pathologically, eight tumors were classified as malignant and one as having uncertain malignancy potential. Half of the tumors showed high MIB-1 index values of > 30%. Immunohistochemically, the melanocyte marker HMB45 was expressed in 89% of the cases, and muscle-specific markers were expressed only in 30-50% of the cases. Transcription factor binding to IGHM enhancer 3 (TFE3) expression was positive in 100% of the patients. Tumors with high expression of TFE3 were classified as PEComas with malignant potential according to Folpe's classification. CONCLUSIONS: Bone and soft tissue PEComas may have a higher malignancy potential than other visceral PEComas and are more likely to develop as TFE3-rearranged PEComas.

[A case of hepatocellular carcinoma showed the usefulness of endoscopic ultrasound-guided fine needle aspiration cytology using the cell block technique for differential diagnosis of gastric submucosal tumor].

A mass lesion presenting difficulty in differential diagnosis between a tumor in the lateral segment of the liver and a gastric submucosal tumor (SMT) was found in a 59-year-old man with chronic hepatitis B. For differential diagnosis between the 2 lesions, endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) was performed. EUS showed a tumor exhibiting a mosaic pattern with a halo derived from the lateral segment of the hepatic left lobe in contact with the stomach. FNA using the cell block technique revealed findings consistent with HCC. No examination-associated complications developed. In patients with HCC that is in contact with the stomach and shows extrahepatically protruding growth, which is difficult to differentiate from gastric SMT, EUS-FNA is a method worthy of trying.

Outcomes of Sarcopenia Treatment for Malignant Bone and Soft Tissue Tumors in Elderly Patients.

Background/Aim: We determined the impact of sarcopenia on the treatment outcomes of malignant bone and soft tissue tumors in elderly patients. Patients and Methods: We retrospectively reviewed 76 patients (age ≥65 years) who were treated for malignant bone and soft tissue tumors. Sarcopenia was assessed by measuring the cross-sectional area of the psoas muscles at the L3 vertebra from preoperative computed tomography images and categorized using the total psoas area/m 2 (TPA/m 2 ) ≤5.0 cm 2 /m 2 . The patients' clinical data were then evaluated. Results: The operation time, length of hospital stay, and median overall survival were not different between the sarcopenia (n=41) and no-sarcopenia (n=35) groups. The local recurrence rate (p=0.01) and incidence of postoperative complications (p=0.02) significantly differed between both groups. The TPA/m 2  of both groups significantly decreased at the final follow-up. Conclusion: Sarcopenia negatively influenced wound healing and local recurrence, and was significantly exacerbated postoperatively in all elderly patients.

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.

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.

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.

In vivo study on the healing of bone defect treated with non-thermal atmospheric pressure gas discharge plasma.

Medical treatment using non-thermal atmospheric pressure plasma (NTAPP) is rapidly gaining recognition. NTAPP is thought to be a new therapeutic method because it could generate highly reactive species in an ambient atmosphere which could be exposed to biological targets (e.g., cells and tissues). If plasma-generated reactive species could stimulate bone regeneration, NTAPP can provide a new treatment opportunity in regenerative medicine. Here, we investigated the impact of NTAPP on bone regeneration using a large bone defect in New Zealand White rabbits and a simple atmospheric pressure plasma (helium microplasma jet). We observed the recovery progress of the large bone defects by X-ray imaging over eight weeks after surgery. The X-ray results showed a clear difference in the occupancy of the new bone of the large bone defect among groups with different plasma treatment times, whereas the new bone occupancy was not substantial in the untreated control group. According to the results of micro-computed tomography analysis at eight weeks, the most successful bone regeneration was achieved using a plasma treatment time of 10 min, wherein the new bone volume was 1.51 times larger than that in the plasma untreated control group. Using H&E and Masson trichrome stains, nucleated cells were uniformly observed, and no inclusion was confirmed, respectively, in the groups of plasma treatment. We concluded the critical large bone defect were filled with new bone. Overall, these results suggest that NTAPP is promising for fracture treatment.