Bone-Regeneration Therapy Using Biodegradable Scaffolds: Calcium Phosphate Bioceramics and Biodegradable Polymers.

Calcium phosphate-based synthetic bone is broadly used for the clinical treatment of bone defects caused by trauma and bone tumors. Synthetic bone is easy to use; however, its effects depend on the size and location of the bone defect. Many alternative treatment options are available, such as joint arthroplasty, autologous bone grafting, and allogeneic bone grafting. Although various biodegradable polymers are also being developed as synthetic bone material in scaffolds for regenerative medicine, the clinical application of commercial synthetic bone products with comparable performance to that of calcium phosphate bioceramics have yet to be realized. This review discusses the status quo of bone-regeneration therapy using artificial bone composed of calcium phosphate bioceramics such as ß-tricalcium phosphate (ßTCP), carbonate apatite, and hydroxyapatite (HA), in addition to the recent use of calcium phosphate bioceramics, biodegradable polymers, and their composites. New research has introduced potential materials such as octacalcium phosphate (OCP), biologically derived polymers, and synthetic biodegradable polymers. The performance of artificial bone is intricately related to conditions such as the intrinsic material, degradability, composite materials, manufacturing method, structure, and signaling molecules such as growth factors and cells. The development of new scaffold materials may offer more efficient bone regeneration.

Muscle strength and functional recovery for soft-tissue sarcoma of the thigh: a prospective study.

BACKGROUND: This study aimed to investigate changes in muscle strength and functional outcome before and after surgery for soft-tissue sarcoma of the thigh and to examine the timing of recovery. METHODS: From 2014 to 2019, 15 patients who underwent multiple resections of the thigh muscle for soft-tissue sarcoma of the thigh were included in this study. The muscle strength was measured with an isokinetic dynamometer for the knee joint and with a hand-held dynamometer for the hip joint. The functional outcome assessment was based on the Musculoskeletal Tumor Society (MSTS) score, Toronto Extremity Salvage Score (TESS), European Quality of Life-5 Dimensions (EQ-5D), and maximum walking speed (MWS). All measurements were conducted preoperatively and at 3, 6, 12, 18, and 24 months postoperatively, and the ratio of postoperative to preoperative value was used. A repeated-measures analysis of variance was performed to compare changes over time and to investigate the recovery plateau. Correlations between changes in muscle strength and functional outcomes were also examined. RESULTS: The muscle strength of the affected limb, MSTS score, TESS, EQ-5D, and MWS were significantly decreased at 3 months postoperatively. The recovery plateau was subsequently reached at 12 months postoperatively. The changes in muscle strength of the affected limb and functional outcome showed a significant correlation. CONCLUSIONS: The estimated postoperative recovery for soft-tissue sarcoma of the thigh is 12 months after surgery.

Influence of the adductor compartment resection on muscle strength and postoperative function in soft-tissue sarcoma of the thigh.

OBJECTIVE: To predict the muscle strength and postoperative function for soft-tissue sarcoma arising from the adductor compartment of the thigh. METHODS: Between 2003 and 2019, 17 cases that underwent resection of the adductor muscle group (adductor longus, adductor magnus, adductor brevis, gracilis and pectineus) for soft-tissue sarcoma in the adductor compartment of the thigh were included. The muscle strength was measured with an isokinetic dynamometer for the knee joint and with a hand-held dynamometer for the hip joint (ratio of affected to unaffected side). The Musculoskeletal Tumor Society score, Toronto Extremity Salvage Score, European Quality of Life-5 Dimensions and maximum walking speed were used to assess postoperative function and examine correlations with muscle strength. RESULTS: In 13 cases that underwent an isolated resection of the adductor compartment, reduced adduction strength correlated with increased number of resected muscles in the adductor muscle group (P < 0.001). Postoperative function was maintained, showing no correlations with adduction strength. In four cases that underwent combined resections of other compartments, a decrease was observed in adduction strength as well as the muscle strength of other resected muscles, in addition to a decline in postoperative function. In the 4 or 5 adductor muscle resection group, the comparison between isolated and combined resection revealed comparable results for adduction strength but a significant decrease in postoperative function for the combined resection group. CONCLUSIONS: Postoperative function can be preserved for isolated adductor compartment resection. Combined resections of multiple muscles in other compartments and most adductor muscles may result in decreased postoperative function.

Points of consideration when performing surgical procedures for proximal femoral bone metastasis.

BACKGROUND: To assess the points of consideration when performing surgical procedures for proximal femoral bone metastasis. METHODS: Fourty patients who underwent surgery for proximal femoral bone metastasis from 2009 to 2019 were included. Prognostic assessments were performed based on the Katagiri scoring system. The low-risk group underwent endoprosthetic replacement (EPR) following resection, while the high-risk group underwent internal fixation (IF). For the intermediate-risk group, one of the surgical procedures was chosen depending on general and local condition. Survival period, walking ability, and treatment failure were evaluated. RESULTS: Sixteen and 24 patients underwent EPR and IF, respectively. Although walking reacquisition rate was 94% (15 of 16 patients) for EPR and 75% (18 of 24 patients) for IF (p = 0.210), the median time to walking was shorter in IF compared to EPR (EPR, 29 days, interquartile range [IQR] 23-40; IF, 14 days, IQR 9-24; p = 0.014). Neither EPR nor IF resulted in treatment failure for those with survival periods of <1 year. The treatment failure rate for those with survival periods of ≥1 year was significantly different between EPR (9%, 1 of 11 patients) and IF (50%, 5 of 10 patients) (p = 0.038). All five patients of treatment failure for IF were renal cancer with no bone formation in the intermediate-risk group. Of the 13 patients who underwent IF for the intermediate-risk group, treatment failure did not occur in 5 patients with bone formation. CONCLUSIONS: Although EPR is a more reliable treatment than IF, patients with life expectancy of <1 year are sufficiently manageable with IF. For the intermediate-risk group, EPR should be selected for cases without expected bone formation, and IF can be considered for cases with expected bone formation due to the risk of treatment failure for IF at ≥ 1 year after surgery.

Antitumor Effect of Sclerostin against Osteosarcoma.

Various risk factors and causative genes of osteosarcoma have been reported in the literature; however, its etiology remains largely unknown. Bone formation is a shared phenomenon in all types of osteosarcomas, and sclerostin is an extracellular soluble factor secreted by osteocytes that prevents bone formation by inhibiting the Wnt signaling pathway. We aimed to investigate the antitumor effect of sclerostin against osteosarcoma. Osteosarcoma model mice were prepared by transplantation into the dorsal region of C3H/He and BALB/c-nu/nu mice using osteosarcoma cell lines LM8 (murine) and 143B (human), respectively. Cell proliferations were evaluated by using alamarBlue and scratch assays. The migratory ability of the cells was evaluated using a migration assay. Sclerostin was injected intraperitoneally for 7 days to examine the suppression of tumor size and extension of survival. The administration of sclerostin to osteosarcoma cells significantly inhibited the growth and migratory ability of osteosarcoma cells. Kaplan-Meier curves and survival data demonstrated that sclerostin significantly inhibited tumor growth and improved survival. Sclerostin suppressed the proliferative capacity and migratory ability of osteosarcoma cells. Osteosarcoma model mice inhibited tumor growth and prolonged survival periods by the administration of sclerostin. The effect of existing anticancer drugs such as doxorubicin should be investigated for future clinical applications.

Distal femoral impaction bone grafting in revision for tumor endoprosthesis.

BACKGROUND: Reconstruction using tumor endoprosthesis has been widely used in cases with large bone defects caused by bone and soft tissue tumor resection of the distal femur which extend into the knee joint. However, reconstruction failure can lead to major problems in the long term. We have been performing impaction bone grafting with allogeneic cancellous bone during revision surgery for tumor endoprosthesis of the distal femur to compensate for the thinness and fragility of the remaining femur. The aim of this study is to examine the surgical method, problems, and clinical outcomes of revision surgery with impaction bone grafting. METHODS: Three patients who underwent revision surgery for tumor endoprosthesis using impaction bone grafting at our institution with more than 2 years of follow-up were included. RESULTS: Union between the graft and host bone were achieved in all cases. The mean time to radiographic union was 1.0 year (0.6-1.5 years). Although intraoperative penetration to the anterior cortex of the distal femur occurred in 2 cases, there were no postoperative fractures. There were no failures of tumor endoprosthesis at final observation. CONCLUSION: Good short-term results were observed in 3 patients who underwent revision tumor endoprosthesis with impaction bone grafting following a bone and soft tissue tumor resection of the distal femur. The method was considered to be a useful treatment option. Impaction bone grafting is an established surgical option that can be applied to revision surgery for tumor endoprosthesis.

Severe Mononeuritis Multiplex due to Rheumatoid Vasculitis in Rheumatoid Arthritis in Sustained Clinical Remission for Decades.

Rheumatoid vasculitis (RV) usually occurs in patients with refractory rheumatoid arthritis (RA). An 80-year-old woman was transferred to our hospital because of muscle weakness and paresthesia in all 4 limbs. She had been diagnosed with RA 30 years ago and achieved sustained clinical remission. At presentation, polyarthritis and drop foot were observed, and rheumatoid factor was prominently elevated. A peripheral nerve conduction test revealed mononeuritis multiplex in her limbs. We suspected that RV had developed rapidly despite RA having been stable for many years and started immunosuppression therapy with steroids combined with azathioprine. The treatment prevented worsening of muscle weakness and paresthesia.

Risk factor for wound complications following wide resection of soft tissue sarcoma in the adductor compartment of the thigh.

BACKGROUND: The purpose of this study was to investigate deep-seated soft tissue sarcoma (STS) occurring in the adductor compartment of the thigh that underwent wide resection and to clarify the high-risk group for wound complications. PATIENTS AND METHODS: From 2000 to 2017, we reviewed 104 cases of deep-seated STS occurring in the adductor compartment of the thigh that were treated at four specialized facilities with expertise in sarcoma treatment. RESULTS: Wound complications occurred in 40 cases (38.5%), of which 23 cases (22.1%) were cases with major wound complications (MWC). In univariate analysis, BMI (P < 0.01), maximum tumor diameter (P < 0.01), operation time (P < 0.01), amount of intraoperative bleeding (P < 0.01), and intraoperative intervention to the femoral artery and vein (P < 0.01) were significantly associated with wound complications. In multivariate analysis, the associated parameters were BMI (P < 0.01), maximum tumor diameter (P = 0.02), and intraoperative intervention to the femoral artery and vein (P = 0.01). When limited to cases with MWC, univariate analysis showed that maximum tumor diameter (P < 0.01), diabetes mellitus (P = 0.03), operation time (P < 0.01), amount of intraoperative bleeding (P < 0.01), and intraoperative intervention to the femoral artery and vein (P = 0.02) were significantly associated parameters. In multivariate analysis, maximum tumor diameter (P = 0.02) and amount of intraoperative bleeding (P = 0.04) were associated parameters. CONCLUSIONS: For patients with risk factors for wound complications, control of bleeding are crucial when resecting deep-seated STS in the adductor compartment of the thigh. In cases with large tumors, surgeons should be especially cautious of cases requiring interventions that surround the femoral artery and vein in order to attain an appropriate surgical margin.

Combined treatment using Mohs' paste and neoadjuvant chemotherapy for giant gluteal soft tissue sarcoma with malignant fungating wound: a case report.

A malignant fungating wound is a cutaneous infiltration of malignant tumor or metastatic lesion that develop into ulceration. Local control is often difficult to obtain, because the Quality of Life of patients can decrease considerably due to bleeding, exudation, odor and pain from the wound. There are few studies in the literature that report the use of Mohs' paste for soft tissue sarcoma with malignant fungating wound. We report a case resulting in good local control for a patient with dedifferentiated liposarcoma with gluteal ulceration by the combined use of Mohs' paste and chemotherapy as a pre-operative adjuvant therapy. Mohs' paste controlled the infection, odor and exudation in approximately 2 weeks, and good visualization of the surgical field was obtained due to tumor volume reduction. We found that Mohs' paste is effective as a neoadjuvant therapy for disintegrated soft tissue sarcoma.

Using the Barthel Index to Assess Activities of Daily Living after Musculoskeletal Tumour Surgery: A Single-centre Observational Study.

OBJECTIVE: The objective of the current study was to find the factors affecting the activities of daily living, as evaluated by the Barthel Index, at the end of rehabilitation after musculoskeletal tumour surgery. Further, we evaluated whether the Barthel Index correlates with functional scores that are specific to musculoskeletal tumours at final follow-up. METHODS: The activities of daily living of 190 patients who underwent postoperative rehabilitation after surgery to treat musculoskeletal tumours were evaluated at the end of the program using the Barthel Index. Functional evaluation at the time of final follow-up observation was evaluated using the Musculoskeletal Tumour Society Score and the Toronto Extremity Salvage Score. RESULTS: The post-rehabilitation Barthel Index was significantly lower in elderly patients aged more than 60 years and in those with malignant tumours and tumours larger than 10 cm. Malignancy and large tumour size were risk factors for a low Barthel Index. There was significant correlation between the Musculoskeletal Tumour Society Score/Toronto Extremity Salvage Score at final functional evaluation and the Barthel Index at the end of rehabilitation. CONCLUSION: The Barthel Index is a simple method to assess the activities of daily living and can potentially predict disease-specific health-related quality of life at final functional evaluation after musculoskeletal tumour surgery.

The status quo of treatment and clinical outcomes for patients over 80 years of age with high-grade soft tissue sarcoma: report from the soft tissue tumor registry in Japan.

OBJECTIVE: The purpose of this study is to clarify the status quo of management and clinical outcome of treatments for oldest-old (≥80 years) patients with high-grade soft tissue sarcomas in Japan. METHOD: The present study was conducted using data from the Soft Tissue Tumor Registry in Japan. There were 956 oldest-old patients with soft tissue sarcoma who were registered from 2006 to 2012. Among them, cases with incomplete data, low-grade soft tissue sarcoma and those who underwent treatment at other institutions were excluded from analysis. RESULTS: We examined 451 cases of high-grade soft tissue sarcoma in oldest-old patients. Three-hundred fifty-one cases (77.8%) were surgically managed, while 100 cases were conservatively managed. In patients aged 85 years and older, 73.1% underwent surgical treatment. A significantly higher proportion of patients underwent conservative therapy in oldest-old patients aged 85 years or older (P = 0.036), patients with deep-seated tumors (P = 0.027) and patients with distant metastases at the first visit (P = 0.000). The median follow-up period was 18.9 months (range, 0.2-83.1). Risk factors for overall survival were extracompartmental tumor progression (P = 0.014) and presence of distant metastases at the first visit (P = 0.000). CONCLUSION: We reported the status quo of treatment and clinical outcome for oldest-old patients with high-grade soft tissue sarcoma in Japan. Although surgery is the primary treatment for soft tissue sarcoma, a significantly higher proportion of patients underwent conservative therapy over surgical treatment in patients aged 85 years or older, patients with deep-seated tumors and patients with distant metastases.

Clinical outcomes of patients 80 years of age and older with soft tissue sarcoma.

OBJECTIVES: Although soft tissue sarcoma (STS) is rare, its incidence is increasing among older patients. Few studies have compared the outcomes between conservative and surgical treatments for STS patients aged ≥80 years. We assessed the outcomes of both treatments in this population and the association between older age and surgical outcome. METHODS: We recruited consecutive patients with STS aged ≥80 years treated at our institution between January 2006 and May 2014. We recommended surgical resection for all patients without multiple distant metastases. Overall survival and sarcoma-specific survival were assessed using the Kaplan-Meier method. RESULTS: Of the 39 patients with STS who presented at our institution, 37 were included in this analysis (19 men and 18 women with a median age of 85 [range 80-94] years). Tumors were classified as Stage IB (n = 3), IIA (n = 6), IIB (n = 3) or III (n = 24). Four patients underwent conservative therapy and 33 underwent surgical resection. The most common tumor site was the lower extremity, and the majority of tumors were classified as undifferentiated pleomorphic sarcoma. The follow-up rate was 100%. One-year sarcoma-specific survival rates were 25.0% in the conservative therapy group and 90.9% in the surgical resection group. No associations were found between age ≥85 years and perioperative complications or clinical outcome. CONCLUSIONS: Surgical resection had relatively few complications, given the age group, and improved the prognosis of older patients with STS. Surgical resection of STS with curative intent should be considered in older patients.

Clinical outcome of dedifferentiated liposarcoma in the extremities: A retrospective case series of 7 patients.

BACKGROUND: Wide resection is the generally recommended surgical treatment for dedifferentiated liposarcoma (DDLPS) in the extremities. However, it may be appropriate to distinguish the surgical margin of low-grade atypical lipomatous tumor (ALT)/well-differentiated liposarcoma (WDLPS) area from the high-grade dedifferentiated area, because the low- and high-grade areas can be clearly separated, both radiologically and histologically. This study re-evaluated the details of surgical margin of DDLPS in the extremities, and aimed to investigate the optimal surgical margin and the usefulness of adjuvant therapy for DDLPS in the extremities. METHODS: Seven patients diagnosed with DDLPS in the extremities and treated between 1995 and 2013 were analyzed. The use of adjuvant therapy before and after surgery was assessed, and the surgical margins for the ALT/WDLPS and dedifferentiated areas were re-evaluated by using the specimens resected at surgery. Subsequently, the recurrence rates, metastatic rates, and oncological outcomes were examined. RESULTS: Four and three patients had wide (adequate wide margin, n = 3; inadequate wide margin, n = 1) and marginal margins for the dedifferentiated area, respectively, while three and four patients had wide (adequate wide margin, n = 2; inadequate wide margin, n = 1) and marginal margins for the ALT/WDLPS area, respectively. Postoperative radiotherapy was performed in three patients with an inadequate wide margin or a marginal margin for the dedifferentiated area. No patient had local recurrence. Distant metastases occurred in two patients. These patients died of their disease. The other five patients were disease-free. CONCLUSION: The ALT/WDLPS and dedifferentiated areas in the tumor margin may be better to be considered separately in determining the appropriate resection extent for DDLPS in the extremities. Postoperative radiotherapy may provide good local control for cases with a narrow surgical margin.

A case of small cell gastric carcinoma with an adenocarcinoma component operated curatively.

We present a case of a primary advanced gastric tumor that was composed of 2 different pathological components: small cell carcinoma and moderately-differentiated adenocarcinoma. The patient was still alive four years after the surgery was performed, without recurrence. A large part of the tumor consisted of a diffuse sheet of small cell carcinoma, which transitioned into another small portion consisting of moderately-differentiated tubular adenocarcinoma components. Therefore, this case raised the possibility that small cell gastric carcinoma may originate from totipotential stem cells of the stomach. Although small cell carcinoma progresses aggressively, and patients with it have an extremely poor prognosis, this patient recovered uneventfully after the surgical resection, and has remained in good health, without any recurrences.