Publications by authors named "Tomoki Nakamura"

148 Publications

Spectrally blue hydrated parent body of asteroid (162173) Ryugu.

Nat Commun 2021 Oct 5;12(1):5837. Epub 2021 Oct 5.

Planetary Exploration Research Center (PERC), Chiba Institute of Technology, Narashino, Chiba, Japan.

Ryugu is a carbonaceous rubble-pile asteroid visited by the Hayabusa2 spacecraft. Small rubble pile asteroids record the thermal evolution of their much larger parent bodies. However, recent space weathering and/or solar heating create ambiguities between the uppermost layer observable by remote-sensing and the pristine material from the parent body. Hayabusa2 remote-sensing observations find that on the asteroid (162173) Ryugu both north and south pole regions preserve the material least processed by space weathering, which is spectrally blue carbonaceous chondritic material with a 0-3% deep 0.7-µm band absorption, indicative of Fe-bearing phyllosilicates. Here we report that spectrally blue Ryugu's parent body experienced intensive aqueous alteration and subsequent thermal metamorphism at 570-670 K (300-400 °C), suggesting that Ryugu's parent body was heated by radioactive decay of short-lived radionuclides possibly because of its early formation 2-2.5 Ma. The samples being brought to Earth by Hayabusa2 will give us our first insights into this epoch in solar system history.
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http://dx.doi.org/10.1038/s41467-021-26071-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8492871PMC
October 2021

Effect of Neoadjuvant Therapies on Soft Tissue Sarcomas with Tail-like Lesions: A Multicenter Retrospective Study.

Cancers (Basel) 2021 Aug 2;13(15). Epub 2021 Aug 2.

Department of Orthopaedic Surgery, Nagoya University Graduate School of Medicine, Nagoya 466-8560, Japan.

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.
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http://dx.doi.org/10.3390/cancers13153901DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8345724PMC
August 2021

Febuxostat reduces muscle wasting in tumor-bearing mice with LM8 osteosarcoma cells via inhibition of reactive oxygen species generation.

Free Radic Res 2021 Jul 19;55(7):810-820. Epub 2021 Jul 19.

Department of Orthopaedic Surgery, Mie university Graduate School of Medicine, Tsu, Japan.

Cachexic condition due to malignant tumors has been a challenging problem. The aim of this study is to analyze effects of febuxostat on both and models of the wasting of skeletal muscles, due to LM8 osteosarcoma cells. C2C12 myotubes were incubated in the conditioned medium of LM8. Febuxostat was added at a concentration of 3 µM and 30 µM, and ROS, diameter of myotubes, and expression of atrogin-1 were analyzed. Furthermore, an study was performed by subcutaneous injection of LM8 on C3H mice. Febuxostat was administered in the drinking water at 5 µg/ml, and 25 µg/ml. In addition, tumor-bearing mice without febuxostat (group TB) and control mice (group C) were established. At 4 weeks, body weight, wet weights of the gastrocnemius muscles, XO activity, 8-OHdG, and expression of TNF-α and IL-6 were evaluated. ROS generation, atrophy of myotubes, and upregulation of atrogin-1 were clearly observed in C2C12 myotubes following incubation in the conditioned medium. These pathological conditions were significantly inhibited by febuxostat administration. Furthermore, mice in group TB showed significant loss of body weight and muscle weight in which XO activity, 8-OHdG, and expression of IL-6 were significantly increased compared to those in group C. Febuxostat administration not only significantly improved the body weight and muscleweight, but also reduced markers of oxidative stress and pro-inflammatory cytokines. Febuxostat did not show anti-tumor effects. Febuxostat, which is clinically used for treatment of hyperuricemia, is effective against the wasting of the skeletal muscles induced by LM8 osteosarcoma cells.
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http://dx.doi.org/10.1080/10715762.2021.1947502DOI Listing
July 2021

Role of the Prognostic Nutritional Index in Patients With Soft-tissue Sarcoma.

In Vivo 2021 Jul-Aug;35(4):2349-2355

Department of Orthopedic Surgery, Mie University Graduate School of Medicine, Tsu, Japan.

Background: This study aimed to determine whether the prognostic nutritional index (PNI) can predict the prognosis in patients with soft-tissue sarcoma (STS) before treatment and to examine whether there is an association between PNI values and clinical characteristics.

Patients And Methods: The data on 100 patients with primary STS were retrospectively reviewed. The cohort included 55 men and 45 women, with a mean age of 64 years. The mean follow-up duration was 41.7 months.

Results: The median PNI was 51.35. The PNI was significantly inversely associated with tumor size, tumor grade, and age. We found that the PNI was a significant prognostic marker for disease-specific and event-free survival using univariate and multivariate analyses. Patients with a low PNI had poorer disease-specific and event-free survival than those with a high PNI.

Conclusion: These results suggest that the PNI can be used as a prognostic marker in patients with STS.
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http://dx.doi.org/10.21873/invivo.12511DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8286482PMC
June 2021

Significance of coagulation and fibrinolysis markers for benign and malignant soft tissue tumors.

BMC Cancer 2021 Apr 7;21(1):364. Epub 2021 Apr 7.

Department of Orthopedic Surgery, Mie University School of Medicine, 2-174 Edobashi, Tsu City, Mie, 514-8507, Japan.

Background: The intimate relationship between coagulation and fibrinolysis in malignant tumors is a well-known phenomena, with the malignant phenotype enhancing coagulation and fibrinolysis. We hypothesized that soft tissue sarcoma (STS) affects the expression of coagulation and fibrinolysis markers, which could be used to distinguish STS from benign soft tissue tumors. We analyzed the correlations between plasma levels of D-dimer (DD), plasmin-α2 plasmin inhibitor complex (PIC), soluble fibrin (SF), and thrombin-antithrombin III complex (TAT) in benign soft tissue tumors and STS to elucidate whether these markers can be used to predict STS.

Methods: Plasma DD, PIC, SF and TAT levels in primary soft tissue tumors (benign 67, STS 68) were measured before biopsy or treatment. The marker levels were analyzed and compared to various clinicopathological parameters.

Results: In malignancy (STS), the average DD, PIC and SF levels were significantly higher than in benign tumors. Multivariate logistic analysis of continuous variables indicated that only PIC exhibited a significant difference (OR: 24.5, 95%CI: 3.55-170, p = 0.0012). Receiver operating characteristic curve analysis produced area under the curve values for DD: 0.691, PIC: 0.784, SF: 0.734 and TAT: 0.588. Youden's index was used to establish thresholds of 0.37 (DD), 0.80 (PIC), 0.90 (SF) and 0.82 (TAT). Threshold values for PIC and SF indicated high specificity (0.881, 0.791) and high positive predictive value (0.818, 0.745), respectively. The highest accuracy value among the markers was observed for PIC (0.704). Significant differences in multivariate analysis of binary variables were demonstrated by categorizing low and high groups based on their threshold, PIC (≥0.80) (OR: 3.36, 95%CI: 1.19-9.43, p = 0.0212) and SF (≥0.90) (OR: 2.63, 95%CI: 1.04-6.66, p = 0.0404) .

Conclusions: Of the coagulation and fibrinolysis markers studied, increased PIC levels were related to STS and over 0.80 PIC was the most suitable for the prediction of STS, which, along with other diagnostic tools, represents a helpful subsidiary tool for the prediction of STS.
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http://dx.doi.org/10.1186/s12885-021-08091-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8028118PMC
April 2021

Is perioperative chemotherapy recommended in childhood and adolescent patients with synovial sarcoma? A systematic review.

Jpn J Clin Oncol 2021 May;51(6):927-931

Department of Musculoskeletal Oncology, National Cancer Center Hospital Tokyo, Japan.

Objective: Synovial sarcoma is the most common soft tissue sarcomas among childhood and adolescents, accounting for 8-10% of all soft tissue sarcoma. Synovial sarcoma is considered a relatively chemosensitive tumor compared with other soft tissue sarcomas. However, the role of perioperative chemotherapy in synovial sarcoma remains controversial. The purpose of this systematic review is to evaluate the role of perioperative chemotherapy in childhood and adolescent patients with synovial sarcoma.

Methods: We evaluated studies published between 1 January 1990 and 31 December 2017. The following databases were searched: MEDLINE, Cochrane database (via PubMed) and Ichushi (in Japanese).

Results: The search yielded 216 articles in English and Japanese. After the initial screening, based on the title and abstract, 160 articles were excluded. As a second screening, we then assessed the full text of the remaining 56 articles for eligibility. Finally, 10 articles were included in the systematic review. Surgical resection with R0 margin alone was recommended because of the excellent results of two prospective studies. Meta-analysis was performed using data from two retrospective studies of 261 patients. Perioperative chemotherapy did not have a significant effect on survival and event-free survival.

Conclusions: We weakly do not recommend perioperative chemotherapy in patients with non-metastatic synovial sarcoma ≤ 5 cm when R0 resection is acquired. There was no consensus concerning the role of perioperative chemotherapy in patients with synovial sarcoma > 5 cm or those with ≤5 cm who undergo R1 or R2 resection.
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http://dx.doi.org/10.1093/jjco/hyab039DOI Listing
May 2021

The incidence of unplanned excision in patients with soft tissue sarcoma: Reports from the Bone and Soft Tissue Tumor registry in Japan.

J Orthop Sci 2021 Feb 5. Epub 2021 Feb 5.

Department of Orthopedic Surgery, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu-city, Mie, 514-8507, Japan.

Background: Due to their rarity, soft tissue sarcomas (STS)s are often treated surgically as unplanned excisions (UE)s before referral to specialists. The Bone and Soft Tissue Tumor (BSTT) registry is a nationwide, organ-specific cancer registry for bone and soft-tissue tumors in Japan. The aim of this study was to elucidate the incidence and risk factors for UEs using data from the BSTT registry.

Methods: Our study comprised 8761 patients with STS including 4826 males and 3935 females, with a mean age of 59 years (range, 0-105 years). Patients were classified into primary STS and UE groups.

Results: Superficial and deep tumors were found in 2533 and 6120 patients, respectively. The mean STS size was 8.6 cm (range, 0.2-49 cm). We identified 6610 patients with high-grade, and 1758 patients with low-grade STS. Of the total 8761 patients, 7770 patients had primary STSs, whereas 991 patients were referred after undergoing UE. The UE mean incidence rate over 11 years was 11.3%. The UE incidence rates for leiomyosarcoma (LMS) (odds ratio [OR] = 1.75, p < 0.0001), fibrosarcoma (FS) (OR = 2.28, p < 0.0001), and epithelioid sarcoma (OR = 1.82, p = 0.01) were higher than the mean UE incidence rate (11.3%). Of 757 patients who underwent UE, 354 (47%) patients had superficial (≤5 cm) STSs, whereas 156 (20.6%) of patients had deep STSs (>5 cm) (p < 0.0001). Logistic regression analysis revealed that UE was frequently associated with males and small, superficial, and trunk STSs.

Conclusions: In the present study, the mean UE incidence rate (11.3%) was significantly different from the individual UE incidence rates of histological diagnoses suggesting that surgeons should consider STS, even with small tumors. Continuous education during training for medical students and surgeons is essential to ensure awareness and correct diagnostic procedures for STS.
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http://dx.doi.org/10.1016/j.jos.2020.12.025DOI Listing
February 2021

Is no additional excision after unplanned excision with positive margins justified in patients with small (≤5 cm) high-grade soft-tissue sarcoma?: Analysis from the Bone and Soft Tissue Tumor registry in Japan.

J Orthop Sci 2021 Feb 3. Epub 2021 Feb 3.

Department of Orthopedic Surgery, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu-city, Mie, 514-8507, Japan.

Background: This study aimed to elucidate the clinical outcomes of patients with small (≤5 cm) high-grade soft tissue sarcoma, who underwent unplanned excision with positive surgical margin, using data from the Bone and Soft Tissue Tumor registry in Japan.

Methods: We examined 174 patients (101 males and 73 females; mean age, 59 years) with primary non-metastatic soft tissue sarcoma. The tumor size was ≤5 cm, and tumor histological grade was high in all patients. The mean follow-up duration was 50 months.

Results: Unplanned excision with R1 and R2 margins was reported in 115 (66%) and 59 patients (34%), respectively. After unplanned excision, immediate additional excision was performed in 154 patients, whereas no additional excision was performed in the remaining 20. Of the 154 patients who underwent additional excision, wide surgical margin resection was achieved in 140 patients, while marginal and intralesional resections were achieved in 10 and 3 patients, respectively. Additionally, 93 patients (60%) underwent reconstruction after additional excision. During the last follow-up, 8 patients died of the disease, 22 developed distant metastasis, and 14 reported local recurrence. The 5-year disease-specific survival rate and 5-year metastasis-free survival rate was 93.5% and 85%, respectively. Tumor depth and additional excision after unplanned excision showed statistical significance in the multivariate analysis. The 5-year metastasis-free survival rate was 89.1% in patients with additional excision and 39.2% in those without. Univariate analysis showed an association between additional excision and local control. The 5-year local recurrence-free survival was significantly worse in patients without additional excision after unplanned excision (52.6%) than in those with additional excision (92.8%).

Conclusion: If unplanned excision is performed in patients with small high-grade soft tissue sarcoma, additional excision is recommended for preventing metastasis, along with necessary preparations for reconstruction.
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http://dx.doi.org/10.1016/j.jos.2020.12.022DOI Listing
February 2021

Clinical Outcome of Dermatofibrosarcoma Protuberance. Report From the Bone and Soft Tissue Tumor (BSTT) Registry in Japan.

In Vivo 2021 Jan-Feb;35(1):611-615

Department of Orthopaedic Surgery, Mie University Graduate School of Medicine, Tsu, Japan.

Background: Owing to its rarity, dermatofibrosarcoma protuberance (DFSP) is often inappropriately excised. After unplanned excision (UE), additional excision is commonly performed. We aimed to elucidate the effect of additional excision after UE.

Patients And Methods: We examined 306 patients with primary DFSP. We analyzed surgical outcomes in 291 patients who received planned excision (PE) or additional excision after UE.

Results: Of 306 patients, 194 received PE and the remaining 112 received UE. Of 112 patients, 97 received additional excision after UE. Additional surgery due to complications was more frequent in patients with UE than in those with PE. The 5-year local recurrence-free rate in patients without additional excision after UE was significantly worse than that in those with additional excision after UE.

Conclusion: If UE is performed, we recommend additional excision for preventing local recurrence; however, the surgical wound should be carefully observed.
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http://dx.doi.org/10.21873/invivo.12298DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7880785PMC
June 2021

Deep vein thrombosis of the upper extremity caused by central venous port in a patient with soft tissue sarcoma: A case report.

Mol Clin Oncol 2020 Dec 23;13(6):89. Epub 2020 Oct 23.

Department of Orthopedic Surgery, Mie University Graduate School of Medicine, Tsu, Mie 514-8507, Japan.

Deep vein thrombosis (DVT) more commonly occurs in the lower extremities, whereas involvement of the upper extremities is rare. The present case report describes the clinical course of the development and treatment of upper extremity DVT (UEDVT) following insertion of an indwelling central venous (CV) port in a patient with soft tissue sarcoma (STS) of the thigh. A 66-year-old man was referred to our hospital for STS treatment. The indwelling CV port was placed via the left subclavian vein, and two courses of neoadjuvant chemotherapy were administered. Two months after the catheter placement, DVT was detected from the left upper arm to the left internal jugular vein. Anticoagulation therapy with warfarin was started and DVT was undetectable at 5 months after surgery. In conclusion, DVT may occur in cancer patients who undergo treatment with indwelling CV ports. Therefore, screening should be conducted concurrently with surgical resection and chemotherapy for STS.
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http://dx.doi.org/10.3892/mco.2020.2160DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7657082PMC
December 2020

Anti-tumour effect of tocilizumab for osteosarcoma cell lines.

Bone Joint Res 2020 Nov;9(11):821-826

Department of Orthopaedic Surgery, Mie University Graduate School of Medicine, Tsu, Japan.

Aims: Tocilizumab, an interleukin-6 (IL-6) receptor (IL-6R) targeting antibody, enhances the anti-tumour effect of conventional chemotherapy in preclinical models of cancer. We investigated the anti-tumour effect of tocilizumab in osteosarcoma (OS) cell lines.

Methods: We used the 143B, HOS, and Saos-2 human OS cell lines. We first analyzed the IL-6 gene expression and IL-6Rα protein expression in OS cells using reverse transcription real time quantitative-polymerase chain reaction (RT-qPCR) analysis and western blotting, respectively. We also assessed the effect of tocilizumab on OS cells using proliferation and invasion assay.

Results: The OS cell lines 143B, HOS, and Saos-2 expressed IL-6R. Recombinant human IL-6 treatment increased proliferation of 143B and HOS cells. Tocilizumab treatment decreased proliferation and invasion of 143B, HOS, and Saos-2.

Conclusion: In conclusion, we confirmed the production of IL-6 and the expression of IL-6R in OS cells and demonstrated that tocilizumab inhibits proliferation and invasion in OS cells. Cite this article: 2020;9(11):821-826.
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http://dx.doi.org/10.1302/2046-3758.911.BJR-2020-0123.R1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7672325PMC
November 2020

Cases of abdominal wall endometriosis distinguished from soft tissue tumors: A report of three cases.

Biomed Rep 2020 Dec 20;13(6):64. Epub 2020 Oct 20.

Department of Orthopaedic Surgery, Mie University Graduate School of Medicine, Tsu-city, Mie 5148507, Japan.

Endometriosis is an estrogen-dependent inflammatory disease characterized by the presence of endometrium-like tissue in sites outside the uterine cavity. It affects 6-10% of women of reproductive age. Concerning abdominal wall endometriosis, it is particularly rare with a reported incidence of 0.03-3.5%. Abdominal wall endometriosis may be misdiagnosed as soft tissue tumors. Patients are often referred to an orthopedic department, although this is not familiar to orthopedic surgeons. In the present report, we describe three women with abdominal painful mass who had previously undergone Caesarean section. The masses were associated with their menstrual cycle and existed proximal to the Caesarean section surgical scar. Pelvic magnetic resonance imaging revealed isointense or hyperintense to muscle on both T1- and T2-weighted images. All patients were suspected of suffering from abdominal wall endometriosis, and were treated with complete surgical resection and developed no recurrence. The pathological findings confirmed endometrial gland and endometrial stroma features. Clinical symptoms and medical history play an important role in the diagnosis of abdominal wall endometriosis in addition to radiological examinations.
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http://dx.doi.org/10.3892/br.2020.1371DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7605119PMC
December 2020

Standard Treatment Remains the Recommended Approach for Patients with Bone Sarcoma Who Underwent Unplanned Surgery: Report from the Japanese Musculoskeletal Oncology Group.

Cancer Manag Res 2020 12;12:10017-10022. Epub 2020 Oct 12.

Department of Orthopaedic Surgery, Osaka National Hospital, Chuo-ku, Osaka 540-0006, Japan.

Background: The outcomes of unplanned surgery for bone sarcomas have not been frequently discussed. However, it is important to recognize patterns, treatment, and clinical outcomes of unplanned surgeries for patients with bone sarcomas. This multicenter study aimed to characterize the clinical outcomes of patients with bone sarcomas who underwent unplanned surgeries.

Patients And Methods: Data of 43 patients with bone sarcomas who underwent unplanned surgery between 2006 and 2017 were obtained from 23 hospitals in Japan. These included 18 cases of osteosarcoma, 9 of Ewing sarcoma, 8 of chondrosarcoma, and 6 of undifferentiated pleomorphic sarcoma. The study included 28 men and 15 women, with a mean age of 46 years. The mean follow-up duration was 59 months.

Results: The main primary tumor sites were the femur (n = 19), spine (n = 6), pelvis (n = 5), tibia (n = 3), and humerus (n = 3). The primary diagnoses were benign bone tumor (n = 24), trauma (n = 7), bone metastasis (n = 5), osteomyelitis (n = 4), degeneration (n=2), and unknown (n = 1). As unplanned surgeries, curettage, with or without bone graft, was performed in 26 patients; internal fixation was performed in 7; spinal surgery in 5; arthroplasty in 4; and arthroscopy in one. Thirty-eight patients received additional standard treatments. Thirty-four of these patients underwent surgical tumor resections, including amputation (n = 10), and the remaining 4 received radiotherapy or carbon ion radiotherapy as additional standard treatments. The 5-year disease-specific survival (DSS) rates in patients with osteosarcoma, Ewing sarcoma, and chondrosarcoma were 65.5%, 58.3%, and 72.9%, respectively. Twelve (27.9%) patients developed local recurrences (LR); among the total 43 patients studied, the 5-year DSS rates were significantly worse for those who developed LR compared to those who did not (p = 0.03). The 5-year DSS rates in patients with and without LR were 44% and 73.8%, respectively.

Conclusion: We recommend that patients who have undergone unplanned surgery be administered standard treatment, including the option of amputation because herein, LR was shown to be a risk factor for decreased DSS.
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http://dx.doi.org/10.2147/CMAR.S270178DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7567545PMC
October 2020

Clinical Outcome of Systemic Treatment for Advanced Soft Tissue Sarcoma: Real-Life Perspective in Japan.

Drug Des Devel Ther 2020 12;14:4215-4220. Epub 2020 Oct 12.

Department of Orthopaedic Surgery, Mie University Graduate School of Medicine, Tsu, Japan.

Introduction: The median survival time of patients with advanced soft tissue sarcoma (STS) is typically <12 months. Since 2012, physicians were able to administer second- and/or third-line treatment easily in Japan, following the approval of new drugs, namely, pazopanib, eribulin, and trabectedin. We investigated the real-life experience of adults with advanced STS who received systemic therapy after the approval of the aforementioned new drugs.

Patients And Methods: We retrospectively evaluated 34 patients (median age: 66 years) with primary STS arising at the extremities/trunk or unresectable local and/or metastatic STS between 2012 and 2019. We evaluated the tumor response and patient survival after initial systemic treatment.

Results: As first-line treatment, doxorubicin and ifosfamide and other drugs were administered to 7 and 27 patients, respectively. Of 31 patients with an evaluable tumor response, partial response was observed in 2 (6.5%) patients, and 16 (52%) patients showed stable disease at 8 weeks. The 1- and 2-year survival rates were 51.4% and 28.4%, respectively. The median overall survival (OS) time was 12.6 months. Tumor response to first-line therapy was related to patient prognosis.

Conclusion: New drugs may be beneficial for patients with advanced STS. When patients cannot receive anthracycline-based chemotherapy because of a high risk of side effects, we believe that the aforementioned drugs may be administered as the first-line treatment.
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http://dx.doi.org/10.2147/DDDT.S275526DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7567542PMC
August 2021

Osteoconductivity of bioactive Ti-6Al-4V implants with lattice-shaped interconnected large pores fabricated by electron beam melting.

J Biomater Appl 2021 04 26;35(9):1153-1167. Epub 2020 Oct 26.

Department of Orthopaedic Surgery, Mie University Graduate School of Medicine, Tsu, Japan.

Additive manufacturing has facilitated the fabrication of orthopedic metal implants with interconnected pores. Recent reports have indicated that a pore size of 600 μm is beneficial for material-induced osteogenesis. However, the complete removal of the metal powder from such small pores of implants is extremely difficult especially in electron beam melting (EBM). We therefore developed a new type of Ti-6Al-4V implant with lattice-shaped interconnected pores measuring 880-1400 μm, which allowed for the easy removal of metal powder. This implant was fabricated by EBM and treated with NaOH, CaCl, heat, and water (ACaHW treatment) to render the metal surface bioactivity. In the present study, the mechanical and chemical property of the implants and the biocompatibility were evaluated. The SEM and micro-CT images demonstrated the 3D interconnectivity of the porous structures. The average porosity of the porous titanium implant was 57.5%. The implant showed maximum compressive load of 78.9 MPa and Young's modulus of 3.57 GPa which matches that of human cortical bone. ACaHW treatment of the porous Ti-6Al-4V implants induced apatite formation in simulated body fluid . The ACaHW-treated porous implants harvested from rabbit femoral bone showed direct bonding of bone to the metal surface without interposition of fibrous tissue. The porous ACaHW-treated implant had a higher affinity to the bone than the untreated one. The mechanical strength of implant fixation assessed using the push-out test was significantly higher in the ACaHW-treated implant than in untreated one. FE-SEM analysis and EDX mapping after push-out test of solid implants showed a lot of bone tissue patches on the surface of the ACaHW-treated implant. These results suggest that the new ACaHW-treated Ti-6Al-4V implant with lattice-shaped interconnected pores is a superior alternative to conventional materials for medical application.
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http://dx.doi.org/10.1177/0885328220968218DOI Listing
April 2021

Prognostic Significance of Thrombomodulin mRNA in High-Grade Soft Tissue Sarcomas after 10 years.

Orthop Surg 2020 Dec 4;12(6):1726-1732. Epub 2020 Oct 4.

Department of Orthopedic Surgery, Mie University School of Medicine, Tsu City, Japan.

Objective: To elucidate the correlation between expression of thrombomodulin (TM) mRNA from 83 benign soft tissue tumors or soft tissue sarcomas (STS) and clinicopathological parameters and to analyze the outcome of high-grade STS patients after 10 years.

Methods: Total RNA was extracted from 83 primary soft tissue tumors (15 benign tumors, 68 STS). TM mRNA normalized to glyceraldehyde-3-phosphate dehydrogenase was measured with real-time quantitative polymerase chain reaction and compared to various clinicopathological parameters. The log-rank test and Cox proportional hazard analysis were used to evaluate recurrence-free survival, metastasis-free survival, and overall survival.

Results: Thrombomodulin mRNA levels were not significantly different between benign tumors and STS. In STS, TM mRNA levels were not significantly different between histologically high-grade (n = 57) and low-grade (n = 11) tumors. Following analysis of high-grade STS at the 10-year follow-up, 21 patients had experienced a recurrence, 22 patients had experienced metastasis, and 23 patients had died of disease (DOD). TM levels were significantly higher in patients with metastasis or DOD patients. Receiver operating characteristic analysis for identifying 5-year and 10-year DOD determined the threshold for best sensitivity and specificity as 0.283. We divided patients into those with high (<0.283) and low (≤0.283) TM mRNA levels. Based on Kaplan-Meier analysis, a significant difference between the two groups was seen for recurrence-free survival (5 years: low = 76.6%, high = 53.1%, 10 years: low: 67.0%, high 39.8%, P = 0.0122) and metastasis-free survival (5 years: low = 86.3%, high = 40.2%, 10 years: low: 73.3%, high: 35.2%, P = 0.00023). Furthermore, the high TM group showed significantly worse prognosis than the low TM group (5 years: low = 90.1%, high = 42.3%, 10 years: low: 76.4%, high 31.3%, P = 0.00031). Thus, high levels of TM mRNA are associated with highly recurrent and metastatic potential and lead to poor prognosis. In multivariate Cox proportional hazard analysis, only high TM showed a significant difference in metastasis-free survival (hazard ratio: 4.33, 95% confidence interval 1.61-11.6, P = 0.00359) and overall survival (hazard ratio: 3.69, 95% confidence interval 1.49-10.5, P = 0.00569).

Conclusion: High levels of TM mRNA may be a significant predictor of recurrence, metastasis, and a poor outcome in STS patients after 10 years. TM is a candidate molecular marker and may be clinically useful for devising a therapeutic treatment strategy by prediction of prognosis.
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http://dx.doi.org/10.1111/os.12779DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7767767PMC
December 2020

Clinical outcome of latissimus dorsi reconstruction after wide resection of soft-tissue sarcoma.

Eur J Orthop Surg Traumatol 2020 Dec 24;30(8):1441-1446. Epub 2020 Jun 24.

Department of Orthopedic Surgery, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu-City, Mie, 514-8507, Japan.

Background: We investigated the clinical outcomes of reconstruction using the latissimus dorsi (LD) flap after resection of soft-tissue sarcoma.

Materials And Methods: We analyzed 19 patients. Free LD flap was performed in 11 patients and pedicle flap in eight patients. The mean follow-up period after the surgery was 60 months.

Results: The mean age at diagnosis was 57 years. The mean tumor size was 9.8 cm. The median size of the LD flap was 140 × 100 mm. The mean surgical duration and bleeding were 510 min and 602 mL, respectively. Complications included partial skin and soft-tissue necrosis (n = 3) and wound dehiscence (n = 2). No additional free flap was not necessary for the closure of the defect due to the complications. The longer surgical duration was significantly associated with wound complications (P = 0.048). The 5-year survival rate was 80.7%, and the local recurrence-free survival rate was 89.2%. Two patients developed local recurrence, while 6 patients developed metastasis. None of the patients had any restrictions of daily life.

Conclusion: The LD flap after surgical tumor resection in patients with soft-tissue sarcoma was useful for the coverage of soft tissue.
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http://dx.doi.org/10.1007/s00590-020-02723-1DOI Listing
December 2020

Vastus lateralis myocutaneous flap for ischial skin wound following the treatment of epithelioid sarcoma using pazopanib.

J Wound Care 2020 Jun;29(6):335-339

Department of Orthopaedic Surgery, Mie University Graduate School of Medicine, Mie, Japan.

Pazopanib, a targeted molecular drug, has been proposed as an effective treatment for soft tissue tumour and as a novel adjuvant therapy. There has been a paradoxical concern that wound healing could be inhibited by its anti-angiogenic properties, especially in reconstructive surgery. This paper reports on a 28-year-old woman who underwent flap surgery due to a skin and soft tissue injury after an effective treatment with pazopanib for refractory epithelioid sarcoma. The flap survived without any complication in off-periods of pazopanib for four weeks before and after the surgery, although it is only recommended that the washout periods of pazopanib commence at least seven days before scheduled surgery.
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http://dx.doi.org/10.12968/jowc.2020.29.6.335DOI Listing
June 2020

Soluble programmed death-ligand 1 rather than PD-L1 on tumor cells effectively predicts metastasis and prognosis in soft tissue sarcomas.

Sci Rep 2020 06 3;10(1):9077. Epub 2020 Jun 3.

Department of Orthopedic Surgery, Mie University School of Medicine, Tsu City, Mie, Japan.

The soluble form of PD-L1 (sPD-L1) is related to a poor prognosis in various cancers. Comparisons of sPD-L1 and PD-L1 expressed on tumor cells in soft tissue tumor patients have not been reported. The purpose of this study was to analyze serum sPD-L1 and PD-L1 levels in soft tissue tumor patients. A total of 135 patients with primary soft tissue tumors were enrolled in this study. The sPD-L1 level was quantitatively measured by enzyme immunoassay, and PD-L1 expression on high grade sarcoma cells was analyzed immunohistologically. There were no significant differences in sPD-L1 levels between benign (48) and soft tissue sarcoma (STS) patients (87). In STS, the high sPD-L1 (>44.26 pg/mL) group had significantly lower metastasis-free survival (MS) and lower overall survival (OS) than the low sPD-L1 group (≤44.26 pg/mL) at 5 years using the log-rank test. On multivariate Cox proportional hazard analysis, the high sPD-L1 group had significant differences in MS and OS compared to the low sPD-L1 group. Between positive and negative immunostaining groups, recurrence-free survival (RS), MS, and OS were not significantly different. No correlation was found between immunostaining and sPD-L1 with the Kappa coefficient. The sPD-L1 concentration could predict future metastasis and prognosis in STS patients. High sPD-L1 in STS patients may be a target for treatment with checkpoint inhibitors.
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http://dx.doi.org/10.1038/s41598-020-65895-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7270095PMC
June 2020

New compounds from Japanese oak wilt disease-associated fungus .

Nat Prod Res 2020 Apr 14:1-7. Epub 2020 Apr 14.

Department of Food, Life, and Environmental Science, Faculty of Agriculture, Yamagata University, Tsuruoka, Yamagata, Japan.

Two new compounds, a new lactone, quercilactone A (), and (17)-hydroxynafuredin (), as well as five known compounds, scytalone (), 3,4-hydoxy-scytalone (), nafuredin (), (+)-(3,5)-3-hydroxy-5-decanolide () and 3-ethyl-4-hydroxy-6-methyl-2-pyran-2-one (), were isolated from , a fungus that causes Japanese oak wilt disease. The structures of these compounds were determined by 1D and 2D NMR spectroscopic analyses. The absolute configuration at C-17 of was determined to be by the modified Mosher's method. Compounds , , and exhibited weak phytotoxic activity in lettuce seedlings at a concentration of 100 μg mL.
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http://dx.doi.org/10.1080/14786419.2020.1753054DOI Listing
April 2020

Expression of Interleukin-6 and the Interleukin-6 Receptor Predicts the Clinical Outcomes of Patients with Soft Tissue Sarcomas.

Cancers (Basel) 2020 Mar 3;12(3). Epub 2020 Mar 3.

Department of Orthopaedic Surgery, Mie University Graduate School of Medicine, Tsu 514-8507, Japan.

Interleukin-6 (IL-6) affects the key parameters of oncogenesis, which increases the cell resistance to apoptosis, the proliferation of cancer cells, angiogenesis, invasion, malignancy, and the ability of tumor cells to respond to anticancer therapy. This study aimed to elucidate the association between IL-6 and IL-6 receptor (IL-6R) expression in tissues and clinical outcomes in patients with soft tissue sarcomas (STSs) because, to our knowledge, this has not been done before. We enrolled 86 patients with histologically-proven localized STSs who underwent surgical resection. The cohort included 48 men and 38 women, with a mean age of 65.6 years. The mean follow-up duration was 40.5 months. The expression of IL-6 and IL-6R was immunohistochemically determined. We analyzed prognostic factors for overall survival (OS) and metastasis-free survival (MFS). High IL-6 expression was observed in 23.3% (20/86), high IL-6R expression in 44.2% (38/86), and high expression of both in 16.3% (14/86) of patients. Multivariate analysis showed that a high expression of both IL-6 and IL-6R was a prognostic factor for OS and MFS. We found that this high expression indicated that the patient had a poor prognosis for OS and MFS.
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http://dx.doi.org/10.3390/cancers12030585DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7139480PMC
March 2020

Temporal analysis of histopathology and cytokine expression in the rat cerebral cortex after insulin-induced hypoglycemia.

Neuropathology 2020 Jun 21;40(3):240-250. Epub 2020 Feb 21.

Laboratory of Veterinary Pathology, Tottori University, Tottori, Japan.

Hypoglycemic coma causes neuronal death in the cerebral neocortex; however, its unclear pathogenesis prevents the establishment of preventive measures. Inflammation plays a pivotal role in neuronal damage in the hypoglycemic state; however, the dynamics of glial cell activation or cytokine expression remain unknown. Here, we aimed to elucidate the spatiotemporal morphological changes of microglia and time-course cytokine expression profiles in the rat cerebral cortex after hypoglycemic coma. We performed histopathological and immunohistochemical (Iba1, neuronal nuclei, glial fibrillary acidic protein) analyses in the cingulate cortex and four areas of the neocortex: hindlimb area (HL), parietal cortex area 1 (Par1), parietal cortex area 2 (Par2), and perirhinal cortex (PRh). We measured tumor necrosis factor alpha (TNFα) and interleukin-6 messenger RNA (mRNA) expression by real-time reverse transcriptase-polymerase chain reaction. Necrotic neurons appeared in the neocortex as early as 3 h after hypoglycemic coma, while they were absent in the cingulate cortex. Neuronal nuclei-immunopositive neurons in the HL, Par2, and PRh were significantly less abundant than in the control at day 1. In Iba1 immunostaining, large rod-shaped cells were detected at 3-6 h after hypoglycemia, and commonly observed in the HL, Par2, and PRh. After 6 h, rod-shaped cells were rarely observed; instead, there was a prominent infiltration of hypertrophic and ameboid-shaped cells until day 7. The mRNA expression of TNFα was significantly higher than the control at 3-6 h after hypoglycemia in the neocortex, while it was significantly higher only at 3 h in the cingulate cortex. Our results indicate that early and transient appearance of rod-shaped microglia and persisting high TNFα expression levels characterize inflammatory responses to hypoglycemic neuronal damage in the cerebral neocortex, which might contribute to neuronal necrosis in response to transient hypoglycemic coma.
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http://dx.doi.org/10.1111/neup.12643DOI Listing
June 2020

Successful combination of endoscopic and laparoscopic removal of multiple ingested needles: A case report.

Medicine (Baltimore) 2020 Feb;99(8):e19343

Department of Internal Medicine, Digestive and Liver Disease Center, Tokai University Tokyo Hospital, Tokyo.

Rationale: Foreign body (FB) ingestion is a relatively common clinical situation in the emergency department. However, multiple sharply pointed foreign bodies located in different organs are rare conditions and no definite treatment guidelines has been established.

Patient Concerns: A 31-year-old amateur magician visited the outpatient clinic with a chief complaint of epigastric discomfort. He might have accidentally swallowed some needles while practicing a magic trick 2 days before.

Diagnosis: Imaging tests revealed 1 needle was stuck in the left liver lobe through the stomach wall, 1 was in the third portion of the duodenum, 3 were in the ascending colon, and 2 were in the transverse colon.

Interventions: A needle in the duodenum and 5 in the colon were removed by endoscopy. The needle stuck in the liver from the stomach was not visible inside the stomach and was successfully removed by laparoscopy a few days later.

Outcomes: The patient was able to tolerate an oral diet and was discharged on postoperative day 4 without any complications.

Lessons: Developing a treatment plan in cases of multiple sharp FB may be difficult. A multidisciplinary team of endoscopists and surgeons is needed to determine the best possible treatment plan. This experience illustrates the importance of the planning of the sequence and method of removal of multiple foreign bodies from the gastrointestinal tract.
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http://dx.doi.org/10.1097/MD.0000000000019343DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7034740PMC
February 2020

Is Serum Lactate Dehydrogenase Useful for Predicting Oncological Outcome in Patients With Soft Tissue Sarcoma?

Anticancer Res 2019 Dec;39(12):6871-6875

Department of Orthopaedic Surgery, Mie University Graduate School of Medicine, Tsu, Japan.

Background/aim: The aim of the present study was to determine whether serum lactate dehydrogenase (LDH) levels before treatment could predict the disease-specific and event-free survival in adult patients with STS.

Patients And Methods: A total of 142 adult patients with primary STS were reviewed. The average follow-up was 73 months with a minimum 2-year follow-up.

Results: Age was significantly associated with LDH. Tumor grade, sex, tumor size, tumor depth, CRP levels, Hb levels and albumin levels were not related. LDH levels were not significantly related to the oncological outcome including disease-specific survival and event-free survival in multivariate analysis. CRP levels were significantly related to the oncological outcome including event-free survival.

Conclusion: Elevated LDH levels prior to initial treatment were not found to be a poor prognostic factor of oncological outcome in adult STS, in both the univariate and multivariate analyses. We recommend routine measurement of the CRP levels for predicting oncological outcome.
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http://dx.doi.org/10.21873/anticanres.13905DOI Listing
December 2019

Histopathological and immunohistochemical analysis of the cerebral white matter after transient hypoglycemia in rat.

J Vet Med Sci 2020 Jan 2;82(1):68-76. Epub 2019 Dec 2.

Laboratory of Veterinary Pathology, Tottori University, Tottori, Tottori 680-8553, Japan.

Patients with hypoglycemic coma show abnormal signals in the white matter on magnetic resonance imaging. However, the precise pathological changes in the white matter caused by hypoglycemic coma remain unclear in humans and experimental animals. This study aimed to reveal the distribution and time course of histopathological and immunohistochemical changes occurring in the white matter during the early stages of hypoglycemic coma in rats. Insulin-induced hypoglycemic coma of 15-30-min duration was induced in rats, followed by recovery using a glucose solution. Rat brains were collected after 6 and 24 hr and after 3, 5, 7, and 14 days. The brains were submitted for histological and immunohistochemical analysis for neurofilament 200 kDa (NF), myelin basic protein, olig-2, Iba-1, and glial fibrillary acidic protein (GFAP). Vacuolation was observed in the fiber bundles of the globus pallidus on days 1-14. Most of the vacuoles were located in GFAP-positive astrocytic processes or the extracellular space and appeared to be edematous. Additionally, myelin pallor and a decrease in NF-positive signals were observed on day 14. Microgliosis and astrogliosis were also detected. Observations similar to the globus pallidus, except for edema, were noted in the internal capsule. In the corpus callosum, a mild decrease in NF-positive signals, microgliosis, and astrogliosis were observed. These results suggest that after transient hypoglycemic coma, edema and/or degeneration occurred in the white matter, especially in the globus pallidus, internal capsule, and corpus callosum in the early stages.
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http://dx.doi.org/10.1292/jvms.19-0502DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6983658PMC
January 2020

Extraterrestrial ribose and other sugars in primitive meteorites.

Proc Natl Acad Sci U S A 2019 12 18;116(49):24440-24445. Epub 2019 Nov 18.

Department of Earth Science, Tohoku University, 980-8578 Sendai, Japan.

Sugars are essential molecules for all terrestrial biota working in many biological processes. Ribose is particularly essential as a building block of RNA, which could have both stored information and catalyzed reactions in primitive life on Earth. Meteorites contain a number of organic compounds including key building blocks of life, i.e., amino acids, nucleobases, and phosphate. An amino acid has also been identified in a cometary sample. However, the presence of extraterrestrial bioimportant sugars remains unclear. We analyzed sugars in 3 carbonaceous chondrites and show evidence of extraterrestrial ribose and other bioessential sugars in primitive meteorites. The C-enriched stable carbon isotope compositions (δC ) of the detected sugars show that the sugars are of extraterrestrial origin. We also conducted a laboratory simulation experiment of a potential sugar formation reaction in space. The compositions of pentoses in meteorites and the composition of the products of the laboratory simulation suggest that meteoritic sugars were formed by formose-like processes. The mineral compositions of these meteorites further suggest the formation of these sugars both before and after the accretion of their parent asteroids. Meteorites were carriers of prebiotic organic molecules to the early Earth; thus, the detection of extraterrestrial sugars in meteorites establishes the existence of natural geological routes to make and preserve them as well as raising the possibility that extraterrestrial sugars contributed to forming functional biopolymers like RNA on the early Earth or other primitive worlds.
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http://dx.doi.org/10.1073/pnas.1907169116DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6900709PMC
December 2019

The Clinical Outcomes of Hemicortical Extracorporeal Irradiated Autologous Bone Graft After Tumor Resection of Bone and Soft Tissue Sarcoma.

Anticancer Res 2019 Oct;39(10):5605-5610

Department of Orthopaedic Surgery, Mie University Graduate School of Medicine, Tsu, Japan.

Background/aim: We analyzed the process of healing at osteotomy sites and timing of achievement of full weight-bearing in sarcoma patients who underwent hemicortical or intercalary reconstruction using the extracorporeal irradiated autologous bone graft technique.

Patients And Methods: We studied 10 patients who had undergone tumor resection and reconstruction with hemicortical extracorporeal irradiated autologous bone graft at mid-shaft femur or tibia. The control group consisted of 30 patients who received the reconstruction using intercalary bone graft.

Results: Full weight-bearing was achieved in all 10 patients at a median time of 4.8 months. Function was excellent in all patients. When comparing the clinical outcome among the patients who received intercalary and hemicortical grafts, the duration to full weight-bearing achievement in patients who received hemicortical graft was shorter than that in those with intercalary graft.

Conclusion: Early full weight-bearing may be achieved in patients undergoing hemicortical resection and reconstruction using extracorporeal irradiated autologous bone graft.
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http://dx.doi.org/10.21873/anticanres.13755DOI Listing
October 2019

Inhibitory effect of edaravone on systemic inflammation and local damage in skeletal muscles following long-term ischemia to murine hind limb.

J Orthop Surg (Hong Kong) 2019 Sep-Dec;27(3):2309499019874470

Department of Orthopaedic Surgery, Graduate School of Medicine, Mie University, Tsu, Japan.

Purpose: The purpose of this study was to evaluate local and systemic pathology in a murine model of ischemia-reperfusion (I/R) injury induced by long-term application of a tourniquet on the hind limbs and to assess the protective effects of edaravone, a potent systemic scavenger of free radicals, using this model.

Methods: Sixty C57BL6 mice were divided in two groups, with one group receiving a 3 mg/kg intraperitoneal injection of edaravone and the other group receiving an identical amount of saline 30 min before ischemia under deep anesthesia. The left thigh of each animal was constricted for 4 h with a 4.5-oz. orthodontic rubber band to induce ischemia; 4 h was the critical duration for skeletal muscles. After ischemia, specimens of skeletal muscles, both kidneys, and plasma were collected at 0, 2, 12, 24, 48, and 72 h. Injury to the skeletal muscles and vacuolar degeneration of the kidneys were histologically assessed. Additionally, apoptosis of skeletal muscle cells was assessed by analysis of caspase 3/7 activity and TUNEL staining. Plasma tumor necrosis factor (TNF)-α levels were measured using an enzyme-linked immunosorbent assay kit.

Results: Skeletal muscles exhibited prominent injury of myofibers at 12 h after I/R injury, with clear upregulation of plasma TNF-α expression and histologic evidence of tubular dysfunction of the kidneys. Plasma TNF-α levels declined and histologic renal damage was ameliorated in edaravone-treated mice, but treatment did not protect skeletal muscle following ischemia for 4 h. Nonetheless, compared with group S, expression of the apoptosis marker caspase 3/7 was significantly inhibited in the skeletal hind limb muscles of Ed-group mice affected by reperfusion injury following ischemia for 4 h.

Conclusion: The present study demonstrated that edaravone is a potentially useful drug for systemic or local treatment of reperfusion injury resulting from long-term ischemia.
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http://dx.doi.org/10.1177/2309499019874470DOI Listing
July 2020

New metabolites produced by endophyte B5 - 2.

Nat Prod Res 2021 May 27;35(9):1525-1531. Epub 2019 Aug 27.

Department of Food, Life, and Environmental Science, Faculty of Agriculture, Yamagata University, Tsuruoka, Yamagata, Japan.

The endophytic fungus, B5-2 was isolated from mangrove plants and subjected to the one strain many compounds (OSMAC) methodology. By this approach, it was found that modification of the culture media enhanced the production of secondary metabolites by B5-2. The apple juice supplemented solid rice media led to significant changes in the secondary metabolism of the fungus, B5-2, and induced the production of four new compounds, (-)-dihydrovertinolide (), and clonostach acids A (), B (), and C () together with the known compound, (-)-vertinolide (). The new compound (-)-dihydrovertinolide () exhibited phytotoxicity against lettuce seedlings at a concentration of 50 mg L.
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http://dx.doi.org/10.1080/14786419.2019.1656629DOI Listing
May 2021

Serum thrombomodulin as a metastatic and prognostic marker in soft tissue sarcomas.

Cancer Biomark 2019 ;26(2):163-170

Department of Orthopedic Surgery, Mie University School of Medicine, Tsu, Mie, Japan.

Background: Thrombomodulin (TM) has multiple biological functions and modulates not only anti-coagulation, but also cell proliferation, adhesion, and anti-inflammation activities. The main function of TM is to activate the anticoagulant pathway of protein C. Soluble TM is related to metastasis by its inactivation of thrombin.

Objectives: To clarify the correlation between serum TM levels and clinicopathological parameters.

Methods: The plasma TM levels (FU/ml) of 135 primary soft tissue tumors (benign, 67; soft tissue sarcoma (STS), 68) were measured before biopsy or treatment. TM levels were analyzed and compared to various clinicopathological parameters. Log-rank test and Cox proportional analysis were used to evaluate recurrence-free survival, metastasis-free survival, and overall survival.

Results: STS tumors had significantly higher TM values (15.9) than benign tumors (13.7) (p= 0.0138). 5-year MFS was 81.1% in low TM and 40.0% in high TM (p= 0.00671), and 5-year OS was 85.5% in low and 52.5% in high TM in grades 1-3 (p= 0.0673). In multivariate COX proportional analysis, high-TM showed a significant difference (MFS: HR 4.37, p= 0.0147; OS: HR 3.60, p= 0.0557) in grades 1-3.

Conclusions: We demonstrated that a high level of soluble TM has the potential to be a significant predictor of metastasis and poor prognosis in STS patients. TM is a candidate molecular marker for high metastatic potential and can be clinically useful for guiding therapeutic strategy.
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http://dx.doi.org/10.3233/CBM-182075DOI Listing
March 2020
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