Publications by authors named "Masao Akagi"

129 Publications

Secondary osteosarcoma associated with osteofibrous dysplasia: a case report.

Skeletal Radiol 2022 Aug 8. Epub 2022 Aug 8.

Department of Orthopaedic Surgery, Kindai University Hospital, Osaka-Sayama City, Osaka, 589-8511, Japan.

Secondary osteosarcoma is a rare complication of primary malignancies and benign bone lesions. There are various types of diseases that cause secondary osteosarcoma. A 15-year-old male presented at our medical center complaining of pain and redness in the right lower leg. He had been diagnosed with osteofibrous dysplasia in the right tibia when he was 2 years old and since then had been followed up. Although he had a pathological fracture of the right tibia at the age of 7, his fracture healed with a plaster cast and did not require surgery. At the time of the patient's last visit, a radiograph revealed a periosteal reaction as well as erosion of the bone cortex. Magnetic resonance imaging revealed an infiltrative area in the soft tissue surrounding the osteofibrous dysplasia lesion in the tibia. Consequent to pathological examination (through bone biopsy), the patient was diagnosed with secondary osteosarcoma. The patient underwent chemotherapy and extensive resection with liquid nitrogen. He has been progressing satisfactorily after the operation. The present case is the first report of secondary osteosarcoma associated with osteofibrous dysplasia. During the long-term follow-up of osteofibrous dysplasia, oncologists should be aware of the possibility of secondary osteosarcoma.
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http://dx.doi.org/10.1007/s00256-022-04122-5DOI Listing
August 2022

Treatment of thigh abscess caused by retroperitoneal perforation of cecal cancer: A case report.

Ann Med Surg (Lond) 2022 Jul 31;79:103882. Epub 2022 May 31.

Departments of Orthopedics and Rheumatology, Kindai University Nara Hospital, 1248-1 Otodacho, Ikoma, Nara, 630-0293, Japan.

Introduction And Importance: Iliopsoas and iliacus abscesses are caused by hematogenous and lymphatic infections and the spread of inflammation in neighboring organs. A small number of cases have been reported in which inflammation spread not only within the iliopsoas muscle but also to the thigh. Here we report a case of retroperitoneal infiltration and perforation of cecal cancer that caused extensive abscess formation from the iliacus muscle to the thigh.

Case Presentation: An 80-year-old man who had undergone chemotherapy for cecal cancer had abdominal pain and right thigh pain without any particular attraction. CT images showed extensive abscess formation from the iliacus muscle to the subcutaneous part of the thigh due to retroperitoneal infiltration and perforation of cecal cancer. Ileocecal resection, colostomy, and retroperitoneal abscess drainage were performed for perforation of cecal cancer and pelvic abscess. Although the thigh was initially drained by a small incision, the infection did not heal. Extensive debridement and drainage were required for all of the contaminated areas, and after all the infection was completely cured.

Clinical Discussion: The optimal treatment for an abscess that has spread from the inguinal region to the thigh is unclear. In this case, active debridement and drainage of the infected area were effective and should have been done early.

Conclusion: We believed that debridement and drainage should have been performed from the time of the first surgery not only by the small incision drainage but also for all of the contaminated areas when the infection had been widespread.
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http://dx.doi.org/10.1016/j.amsu.2022.103882DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9289228PMC
July 2022

PD-1, PD-L1, NY-ESO-1, and MAGE-A4 expression in cutaneous angiosarcoma: A case report.

Medicine (Baltimore) 2022 Jul 15;101(28):e29621. Epub 2022 Jul 15.

Department of Orthopedic Surgery, Kindai University Hospital, Osaka-Sayama City, Osaka, Japan.

Rationale: The genomic alteration of cutaneous angiosarcoma (cAS) is complex. Treatment efficacy of immunotherapy for cAS remains controversial and prognosis remains poor. Herein, we report a case of cAS with programmed cell death 1, programmed cell death ligand-1, New York esophageal squamous cell carcinoma-1, and melanoma-associated antigen 4.

Patient Concerns: A 69-year-old man presented with a chief complaint of left thumb pain, with a soft tissue mass in the palmar side of the thumb. He had no past medical history. Three months prior, the man experienced the pain while scuba diving. He visited a nearby clinic, and magnetic resonance imaging revealed a soft tissue tumor on the palmar side of the thumb. He was referred to our hospital and a marginal excisional biopsy was performed.

Diagnosis: Pathological findings revealed an angiosarcoma with high-flow serpentine vessels.

Interventions: An excision was performed from the base of the thumb to achieve a wide margin.

Outcomes: One year after the treatment, the patient has not experienced recurrence, metastasis, or complications.

Lessons: Histopathology of the excised specimen was positive for programmed cell death 1, programmed cell death ligand-1, New York esophageal squamous cell carcinoma-1, and melanoma-associated antigen 4; their expression may be a therapeutic target for cAS. Combining immunotherapy with surgical treatment may be effective for cAS.
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http://dx.doi.org/10.1097/MD.0000000000029621DOI Listing
July 2022

A direct referencing method of the tibial plateau for the posterior tibial slope in medial unicompartmental knee arthroplasty.

J Orthop Surg Res 2022 Jun 25;17(1):329. Epub 2022 Jun 25.

Department of Orthopaedic Surgery, Kindai University Hospital, 377-2 Ohno-Higashi, Osaka-Sayama City, Osaka, 589-8511, Japan.

Purpose: There is no consensus on intraoperative references for the posterior tibial slope (PTS) in medial unicompartmental knee arthroplasty (UKA). An arthroscopic hook probe placed on the medial second quarter of the medial tibial plateau (MTP) in an anteroposterior direction may be used as a direct anatomical reference for the PTS. The purpose of this study is to investigate the availability and accuracy of this method.

Methods: Marginal osteophyte formation and subchondral depression of the MTP and angles between the bony MTP and the cartilage MTP were retrospectively evaluated using preoperative sagittal MRI of 73 knees undergoing medial UKA. In another 36 knees, intraoperative lateral knee radiographs with the probe placed on the MTP were prospectively taken in addition to the preoperative MRI. Then, angles between the bony MTP and the probe axis and angles between the preoperative bony MTP and the postoperative implant MTP were measured.

Results: Among 73 knees, one knee with grade 4 osteoarthritis had a posterior osteophyte higher than the most prominent point of the cartilage MTP. No subchondral depression affected the direct reference of the MTP. The mean angle between the bony MTP and the cartilage MTP was -0.8° ± 0.7° (-2.6°-1.0°, n = 72), excluding one knee with a "high" osteophyte. The mean angle between the bony MTP and the probe axis on the intraoperative radiograph was -0.6° ± 0.4° (-1.7-0.0, n = 36). The mean angle between the pre- and postoperative MTP was -0.5° ± 1.5° (-2.9°-1.8°). The root-mean-square (RMS) error of these two PTS angles was 1.6° with this method.

Conclusion: Cartilage remnants, osteophyte formation and subchondral bone depression do not affect the direct referencing method in almost all knees for which medial UKA is indicated. When the posterior "high" osteophyte of the MTP is noted on preoperative radiography, preoperative MRI or CT scan is recommended to confirm no "high" osteophyte on the medial second quarter. The accuracy of this method seems equal to that of robotic-assisted surgery (the RMS error in previous reports, 1.6°-1.9°).
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http://dx.doi.org/10.1186/s13018-022-03179-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9233832PMC
June 2022

Clinicopathological assessment of cancer/testis antigens NY‑ESO‑1 and MAGE‑A4 in osteosarcoma.

Eur J Histochem 2022 Jun 23;66(3). Epub 2022 Jun 23.

Department of Orthopedic Surgery, Kindai University Hospital, Osaka-Sayama City, Osaka.

The cancer/testis antigens (CTAs), New York esophageal squamous cell carcinoma-1 (NY-ESO-1) and melanoma antigen gene (MAGE)-A4 are normally restricted to male germ cells but are aberrantly expressed in several cancers. Considering the limited information regarding their significance in osteosarcoma (OS), the purpose of this study was to determine the clinical significance of NY-ESO-1 and MAGE-A4 expression in OS. Nine patients with OS treated at Kindai University Hospital were included in the study. The median age was 27 years, and median follow-up period was 40 months. The specimens obtained at the time of biopsy were used to perform immunostaining for NY-ESO, MAGE-A4, p53, and Ki-67. The positive cell rates and positive case rates of NY-ESO, MAGE-A4, p53, and Ki-67 were calculated. The correlation between the positive cell rate of immunohistochemical markers was also calculated. The correlation between the positive cell rate of NY-ESO-1 or MAGE-A4 and tumor size or maximum standardized uptake (SUV-max) was also determined. The positive cell rates of NY-ESO-1 or MAGE-A4 in continuous disease-free (CDF) cases were also compared with those in alive with disease (AWD) or dead of disease (DOD) cases. The average positive cell rates of NY-ESO, MAGEA4, p53, and Ki-67 were 71.7%, 85.1%, 16.2%, and 14.7%, and their positive case rates were 33.3%, 100%, 44.4%, and 100%, respectively. The positivity rates of NY-ESO-1 and p53 were strongly correlated, whereas those of NY-ESO-1 and Ki-67 were moderately correlated. The MAGE-A4 and p53 positivity rates and the MAGE-A4 and Ki-67 positive cell rates were both strongly correlated. The NY-ESO-1 and MAGE-A4 positivity rates were moderately correlated. The positive correlation between the NY-ESO-1 positive cell rate and tumor size was medium, and that between the MAGE-A4 positivity rate and SUV-max was very strong. There was no significant difference in the positive cell rates of NY-ESO-1 or MAGE-A4 between CDF cases and AWD or DOD cases. Overall, our results suggest that NY-ESO-1 and MAGE-A4 may be involved in the aggressiveness of OS.
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http://dx.doi.org/10.4081/ejh.2022.3377DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9251608PMC
June 2022

Adipose-derived exosomes block muscular stem cell proliferation in aged mouse by delivering miRNA Let-7d-3p that targets transcription factor HMGA2.

J Biol Chem 2022 07 6;298(7):102098. Epub 2022 Jun 6.

Institute of Advanced Clinical Medicine, Kindai University Hospital, Osaka-Sayama, Osaka, Japan. Electronic address:

Sarcopenia is an aging-associated attenuation of muscular volume and strength and is the major cause of frailty and falls in elderly individuals. The number of individuals with sarcopenia is rapidly increasing worldwide; however, little is known about the underlying mechanisms of the disease. Sarcopenia often copresents with obesity, and some patients with sarcopenia exhibit accumulation of peri-organ or intra-organ adipose tissue as ectopic fat deposition, including atrophied skeletal muscle. In this study, we showed that transplantation of the perimuscular adipose tissue (PMAT) to the hindlimb thigh muscles of young mice decreased the number of integrin α7/CD29-double positive muscular stem/progenitor cells and that the reaction was mediated by PMAT-derived exosomes. We also found that the inhibition of cell proliferation was induced by Let-7d-3p miRNA that targets HMGA2, which is an important transcription factor for stem cell self-renewal, in muscular stem/progenitor cells and the composite molecular reaction in aged adipocytes. Reduction of Let-7 miRNA repressor Lin28 A/B and activation of nuclear factor-kappa B signaling can lead to the accumulation of Let-7d-3p in the exosomes of aged PMAT. These findings suggest a novel crosstalk between adipose tissue and skeletal muscle in the development of aging-associated muscular atrophy and indicate that adipose tissue-derived miRNAs may play a key role in sarcopenia.
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http://dx.doi.org/10.1016/j.jbc.2022.102098DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9257422PMC
July 2022

Malignant giant cell tumor of toe: A case report and review of literature.

Medicine (Baltimore) 2022 Jun 3;101(22):e29471. Epub 2022 Jun 3.

Department of Orthopedic Surgery, Kindai University Hospital, Osaka-Sayama City, Japan.

Introduction: A giant cell tumor of soft tissue (GCST) is a benign soft tissue tumor that often occurs subcutaneously in the extremities. Rare cases of malignant GCST have been reported, but its pathogenesis remains unclear.

Patients Concerns: We report a case of a 68-year-old man who noticed a painless mass on his second toe one and a half years ago. He visited the Department of Dermatology at our hospital. Magnetic resonance imaging revealed a soft tissue tumor, surrounding the distal aspect of the second toe.

Diagnosis: A biopsy of the tumor was performed by a dermatologist, and it revealed a malignant giant cell tumor of the toe.

Interventions: He was referred to our department and underwent lay amputation for wide-margin resection.

Outcomes: No recurrence or metastasis was observed 5 years after treatment.

Conclusion: : Malignant GCST should be treated with wide-margin resection immediately after its diagnosis.
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http://dx.doi.org/10.1097/MD.0000000000029471DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9276190PMC
June 2022

Immunohistochemical expression and clinicopathological assessment of PD-1, PD-L1, NY-ESO-1, and MAGE-A4 expression in highly aggressive soft tissue sarcomas.

Eur J Histochem 2022 Apr 22;66(2). Epub 2022 Apr 22.

Department of Orthopedic Surgery, Kindai University Hospital, Osaka-Sayama City, Osaka.

Immunotherapy has altered the treatment paradigm for soft tissue sarcomas (STSs). Considering the limited information regarding the clinical significance of immunohistochemical markers in STS, the purpose of this study was to determine the clinical significance of programmed cell death-1 (PD-1), PD ligand-1 (PD-L1), New York esophageal squamous cell carcinoma-1 (NY-ESO-1), and melanoma-associated antigen-A4 (MAGE-A4) expression in STSs. Twenty-two patients (median age, 72.5 years) with STSs treated at our hospital were included in this study. The specimens obtained at the time of biopsy were used to perform immunostaining for PD-1, PD-L1, NY-ESO, and MAGE-A4. The rates of PD-1-, PD-L1-, NY-ESO-, and MAGE-A4-positive cells and cases were calculated. The correlations among the positive cell rates of the immunohistochemical markers as well as their correlations with the histological grade, tumor size, or maximum standardized uptake (SUVmax) value were also determined. The average rates of PD-1-, PD-L1-, NY-ESO-, and MAGE-A4-positive cells were 4.39%, 28.0%, 18.2%, and 39.4%, respectively. Although the PD-1-positive cell rate showed no correlation with the rates of NY-ESO-1- and MAGE-A4-positive cells, the PD-L1-positive cell rates showed strong positive correlations with the rates of NY-ESO-1- and MAGE-A4-positive cells. PD-1-, PD-L1-, NY-ESO-1-, and MAGE-A4-positive cell rates showed weak to moderate correlations with histological grade or tumor size, while the PD-1-, PD-L1-, and MAGE-A4-positive cell rates showed strong to very strong positive correlations with the SUVmax value. Thus, PD-1, PD-L1, NY-ESO, and MAGE-A4 expressions are correlated and may be involved in the aggressive elements of STSs.
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http://dx.doi.org/10.4081/ejh.2022.3393DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9046686PMC
April 2022

Clinicopathological Assessment of Cancer/Testis Antigens NY-ESO-1 and MAGE-A4 in Highly Aggressive Soft Tissue Sarcomas.

Diagnostics (Basel) 2022 Mar 17;12(3). Epub 2022 Mar 17.

Department of Orthopedic Surgery, Kindai University Hospital, Osakasayama 589-8511, Japan.

We aimed to investigate the clinical significance of the expression of NY-ESO-1 and MAGE-A4 in soft tissue sarcoma (STS). Immunostaining for NY-ESO-1, MAGE-A4, and Ki67 was performed using pathological specimens harvested from 10 undifferentiated pleomorphic sarcoma (UPS), nine myxofibrosarcoma (MFS), and three malignant peripheral nerve sheath tumor (MPNST) patients treated at our hospital. We examined the correlation of NY-ESO-1 and MAGE-A4 expression levels with tumor size, histological grade, and SUVmax values. Positive cell rates of various markers were also compared between patients in remission and those who were not in remission. The rates of cases positive for NY-ESO, MAGE-A4, and Ki67 were 50%, 63.6%, and 90.9%, respectively. The average rates of cells positive for NY-ESO, MAGE-A4, and Ki67 in all STS types were 18.2%, 39.4%, and 16.8%, respectively. A positive correlation was observed between rates of cells positive for NY-ESO-1 and MAGE-A4 and between NY-ESO-1 and MAGE-A4 expression levels and clinical features. There was no significant difference in the positive cell rate of NY-ESO-1 or MAGE-A4 between remission and non-remission cases. Our results suggest that NY-ESO-1 and MAGE-A4 expression may be useful for the diagnosis and prognostication of UPS, MFS, and MPNST.
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http://dx.doi.org/10.3390/diagnostics12030733DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8946957PMC
March 2022

Myxoid liposarcoma originating in the retroperitoneum with metastasis to the calcaneus: a rare case report and review of literature.

Skeletal Radiol 2022 Mar 6. Epub 2022 Mar 6.

Department of Orthopaedic Surgery, Kindai University Hospital, 377-2 Ohno-higashi, Osaka-Sayama City, Osaka, 589-8511, Japan.

Myxoid liposarcoma (MLPS) is known to have a variety of metastatic manifestations. We report a MLPS originating in the pelvis with metastasis to the calcaneus. The patient was a 72-year-old man who developed lumbar pain and right lower extremity pain 2 years ago. He visited a nearby clinic and underwent a radiographic examination. Computed tomography (CT) revealed a tumor in the right retroperitoneum. A CT-guided needle biopsy was performed, and pathological examination revealed myxoid liposarcoma. Wide surgical resection was not performed due to the patients' wishes, technical difficulties, and magnitude of the invasion, and the patient received heavy particle radiation therapy (HPRT) of 70.4 Gy. After HPRT, the tumor mass was slightly reduced. However, 11 months after HPRT, a recurrent lesion in the liver was observed. Although HPRT was performed again for the metastatic liver lesion (70.4 Gy), the tumor increased in size. Furthermore, 1 month later, the patient complained of pain in the left foot, and CT and magnetic resonance imaging revealed an osteolytic lesion in the calcaneus. A biopsy was performed, and pathological examination showed a metastatic lesion of myxoid-type liposarcoma. The patient wore a short lower limb orthosis and was able to walk but died 1 month later. Oncologists should note that MLPS can metastasize to the calcaneus.
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http://dx.doi.org/10.1007/s00256-022-04028-2DOI Listing
March 2022

Depletion of NIMA-related kinase Nek2 induces aberrant self-renewal and apoptosis in stem/progenitor cells of aged muscular tissues.

Mech Ageing Dev 2022 01 4;201:111619. Epub 2022 Jan 4.

Institute of Advanced Clinical Medicine, Kindai University Hospital, Japan. Electronic address:

Frailty of the locomotory organs has become a widespread problem in the geriatric population. The major factor leading to frailty is an age-associated decrease in muscular mass and a reduced number of muscular cells and myofibers. In aged muscular tissues, muscular satellite cells (MuSCs) are reduced due to abnormalities in their self-renewal and the induction of apoptosis. However, the molecular mechanisms connecting aging-associated physiological changes and the reduction of MuSCs are largely unknown. NIMA-related kinase 2 (Nek2), a member of the Nek family of serine/threonine kinases, was found to be downregulated in aged MuSCs/progenitors. Further, Nek2 downregulation was found to inhibit self-renewal and apoptotic cell death by activating the p53-dependent checkpoint. Attenuated NEK2 expression was also observed in the muscular tissues of elderly donors, and its function was confirmed to be conserved in humans. Overall, this study proposes a novel mechanism for inducing muscular atrophy to understand aging-associated muscular diseases.
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http://dx.doi.org/10.1016/j.mad.2022.111619DOI Listing
January 2022

The Medial Tibial Plateau Can Be Used as a Direct Anatomical Reference for the Posterior Tibial Slope in Medial Unicompartmental Knee Arthroplasty.

J Knee Surg 2021 Dec 17. Epub 2021 Dec 17.

Department of Orthopaedic Surgery and Rheumatology, Kindai University Nara Hospital, Ikoma City, Nara Prefecture, Japan.

There has been no consensus about how to determine the individual posterior tibial slope (PTS) intraoperatively. The purpose of this study was to investigate whether the tibial plateau could be used as a reference for reproducing individual PTS during medial unicompartmental knee arthroplasty (UKA). Preoperative computed tomography (CT) data from 48 lower limbs for medial UKA were imported into a three-dimensional planning software. Digitally reconstructed radiographs were created from the CT data as the lateral knee plain radiographs and the radiographic PTS angle was measured. Then, the PTS angles on the medial one-quarter and the center of the MTP (¼ and ½ MTP, respectively), and that on the medial tibial eminence (TE) were measured on the sagittal multiplanar reconstruction image. Finally, 20 lateral knee radiographs with an arthroscopic probe placed on the ¼ and the ½ MTP were obtained intraoperatively, and the angle between the axis of the probe and the tangent line of the plateau was measured. The mean radiographic PTS angle was 7.9 ± 3.0 degrees (range: 1.7-13.6 degrees). The mean PTS angles on the ¼ MTP, the ½ MTP, and the TE were 8.1 ± 3.0 degrees (1.2-13.4 degrees), 9.1 ± 3.0 degrees (1.4-14.7 degrees), and 9.9 ± 3.1 degrees (3.1-15.7 degrees), respectively. The PTS angles on the ¼ MTP and the ½ MTP were strongly correlated with the radiographic PTS angle ( =0.87 and 0.80, respectively,  < 0.001). A statistically significant difference was observed between the mean angle of the radiographic PTS and the PTS on the TE ( < 0.01). The mean angle between the axis of the probe and the tangent line of the tibial plateau was -0.4 ± 0.9 degrees (-2.3-1.3 degrees) on the ¼ MTP and -0.1 ± 0.7 degrees (-1.5-1.2 degrees) on the ½ MTP, respectively. An area from the medial one-quarter to the center of the MTP could be used as an anatomical reference for the individual PTS.
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http://dx.doi.org/10.1055/s-0041-1740384DOI Listing
December 2021

Characterization of PD-1/PD-L1 immune checkpoint expression in the pathogenesis of musculoskeletal Langerhans cell histiocytosis: A retrospective study.

Medicine (Baltimore) 2021 Oct;100(43):e27650

Department of Orthopedic Surgery, Kindai University Hospital, Osaka-Sayama City, Osaka, Japan.

Abstract: Recent data suggest that programmed cell death -1 (PD-1) and programmed cell death ligand-1 (PD-L1) are involved in the pathogenesis of Langerhans cell histiocytoma (LCH); however, their contributions are not well established. Also, the involvement of PD-1/PD-L1 molecules in musculoskeletal LCH remains particularly unclear. The current study aims to characterize the involvement of PD-1/PD-L1 immune checkpoint system in the pathogenesis of musculoskeletal LCH. PD-1/PD-L1 expression was evaluated in 6 patients, 3 men and 3 women with a mean age of 13.5 years, with musculoskeletal LCH who were treated at Kindai University Hospital and Osaka Women's and Children's Hospital between November 2005 and December 2020. The median follow-up period for all patients with musculoskeletal LCH was 41 months. We surveyed symptoms, number of lesions, treatment modality, and outcomes. Immunostaining for CD4, CD8, PD-1, and PD-L1 was also performed on pathological specimens obtained by biopsy. Multiple lesions were observed in 5 cases, and a single lesion was observed in 1 case. The chief complaint in 5 cases was pain. Four patients underwent spontaneous regression. The other 2 patients received chemotherapy. The outcomes included continuous disease-free (n = 5) and alive with the disease (n = 1). The CD4-, CD8-, PD-1-, and PD-L1-positive rates among all specimens were 100%, 100%, 16.6%, and 83.3%, respectively. The CD4/PD-L1, CD8/PD-L1, and PD-1/PD-L1 positive rates in all the specimens were 83.3%, 83.3%, and 16.6%, respectively. We believe that the PD-1/PD-L1 immune checkpoint molecules may play some role in the microenvironment of musculoskeletal LCH.
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http://dx.doi.org/10.1097/MD.0000000000027650DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8556058PMC
October 2021

Rapidly progressive osteoarthritis in the medial patellar facet due to lateral femoral placement after medial unicompartmental knee arthroplasty. A case report.

Int J Surg Case Rep 2021 Nov 7;88:106483. Epub 2021 Oct 7.

Department of Orthopedic Surgery, Kindai University Hospital, 377-2 Ohno-Higashi, Osaka-Sayama City, Osaka 589-8511, Japan. Electronic address:

Introduction And Importance: Factors that affect patellofemoral (PF) osteoarthritis (OA) after unicompartmental knee arthroplasty (UKA) remain unclear. We report a case in which the lateral placement of the femoral component resulted in rapidly progressive OA in the medial patellar facet.

Case Presentation: The patient was an 84-year-old woman who had increased pain in the left knee due to varus knee OA for 1 year and underwent medial UKA. One month after the surgery, the patient complained of limited knee flexion of 90° with anterior knee pain, and around 7-mm lateral placement of the femoral component was observed on a postoperative radiograph and computed tomography scan. Six months after the surgery, rapidly progressive OA with subchondral bone depression in the medial facet was observed and this has been ongoing till the last follow-up of 3 years. The knee flexion is limited 105° now, and the patient complains of quadriceps weakness with anterior knee pain when stair-climbing and standing up from a chair.

Clinical Discussion: Lateral placement of the femoral component in medial UKA may cause progressive PF OA with limited knee flexion and anterior knee pain, which could be attributed to impingement between the femoral component and the medial patellar facet.

Conclusion: Surgeons should be careful regarding the lateral placement to prevent symptomatic PF OA from occurring after medial UKA.
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http://dx.doi.org/10.1016/j.ijscr.2021.106483DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8602739PMC
November 2021

Bone marrow-derived mesenchymal stem cells transplanted into a vascularized biodegradable tube containing decellularized allogenic nerve basal laminae promoted peripheral nerve regeneration; can it be an alternative of autologous nerve graft?

PLoS One 2021 31;16(8):e0254968. Epub 2021 Aug 31.

Department of Orthopedic Surgery, Kindai University Hospital, Osakasayama, Osaka, Japan.

Previously, we showed silicone nerve conduits containing a vascular bundle and decellularized allogenic basal laminae (DABLs) seeded with bone marrow-derived mesenchymal stem cells (BMSCs) demonstrated successful nerve regeneration. Nerve conduits should be flexible and biodegradable for clinical use. In the current study, we used nerve conduits made of polyglycoric acid (PGA) fiber mesh, which is flexible, biodegradable and capillary-permeable. DABLs were created using chemical surfactants to remove almost all cell debris. In part 1, capillary infiltration capability of the PGA tube was examined. Capillary infiltration into regenerated neural tissue was compared between the PGA tube with blood vessels attached extratubularly (extratubularly vascularized tube) and that containing blood vessels intratubularly (intratubularly vascularized tube). No significant difference was found in capillary formation or nerve regeneration between these two tubes. In part 2, a 20 mm gap created in a rat sciatic nerve model was bridged using the extratubularly vascularized PGA tube containing the DABLs with implantation of isogenic cultured BMSCs (TubeC+ group), that containing the DABLs without implantation of the BMSCs (TubeC- group), and 20 mm-long fresh autologous nerve graft (Auto group). Nerve regeneration in these three groups was assessed electrophysiologically and histomorphometrically. At 24 weeks, there was no significant difference in any electrophysiological parameters between TubeC+ and Auto groups, although all histological parameters in Auto group were significantly greater than those in TubeC+ and TubeC- groups, and TubeC+ group demonstrated significant better nerve regeneration than TubeC- group. The transplanted DABLs showed no signs of immunological rejection and some transplanted BMSCs were differentiated into cells with Schwann cell-like phenotype, which might have promoted nerve regeneration within the conduit. This study indicated that the TubeC+ nerve conduit may become an alternative to nerve autograft.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0254968PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8407554PMC
November 2021

Limitations and usefulness of biopsy techniques for the diagnosis of metastatic bone and soft tissue tumors.

Ann Med Surg (Lond) 2021 Aug 16;68:102581. Epub 2021 Jul 16.

Department of Orthopedic Surgery, Kindai University Hospital, Osaka-Sayama City, Osaka, 589-8511, Japan.

Background: Biopsies are widely used for diagnosing metastatic tumors in the bone and soft tissues; however, their usefulness and limitations remain unclear.

Patients And Methods: Biopsies of patients (13 men, 8 women, mean age 76 years) with metastatic tumors in the bone (19 patients) and soft tissues (2 patients) were reviewed retrospectively. Investigators surveyed the lesion sites, medical histories, Eastern Cooperative Oncology Group (ECOG) Performance Status (PS), biopsy sites, methods, comorbidities, diagnoses, treatments, and outcomes.

Results: Five patients had multiple lesions, and 16 patients had one lesion. The ECOG PS scores were PS0 (11 patients), PS1 (7 patients), PS2 (2 patients), and PS3 (1 patient). Biopsy sites included pelvic bone (6 cases), rib bone (5 cases), spinal vertebra (7 cases), soft tissue of the shoulder (2 cases), and inner retroperitoneum (1 case). Diagnostic methods included open biopsy (8 patients), core needle biopsy under general (7 patients) or local (3 patients) anesthesia, and computed tomography-guided core needle biopsy under local anesthesia (3 patients). Histology indicated hematological malignancies (9 cases); breast cancer (3 patients); lung cancer, renal cell cancer, cancer of unknown primary (2 cases each); prostate cancer, endometrial (uterine) cancer, and myxoid liposarcoma (1 case each). The primary site identification rate was 90.5%. Outcomes included three patients "dead of disease."

Conclusion: Biopsies are useful for early diagnosis and for the scrutiny of primary lesions of metastatic bone and soft tissue tumors. If the primary tumor is still unknown after biopsy, evidence-based treatment should be initiated promptly.
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http://dx.doi.org/10.1016/j.amsu.2021.102581DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8318849PMC
August 2021

Characterization of PD-1/PD-L1 immune checkpoint expression in soft tissue sarcomas.

Eur J Histochem 2021 Jul 2;65(3). Epub 2021 Jul 2.

Department of Orthopedic Surgery, Kindai University Hospital, Osaka-Sayama City, Osaka.

Inhibitors of the programmed death-1/programmed death-ligand 1 (PD-1/PD-L1) immune checkpoint system are used for treating various malignancies. However, evidence on their use in soft tissue sarcomas (STS) is limited. This study aimed to retrospectively investigate the relationship between the expression of PD-1/PD-L1 and related antigens in STS, and their association with clinical characteristics. Immunostaining for CD4, CD8, PD-1, PD-L1, IL-2, and IFN-γ was performed using pathological specimens harvested at the time of biopsy from 10 patients with undifferentiated pleomorphic sarcoma (UPS), nine with myxofibrosarcoma (MFS), and three with malignant peripheral nerve sheath tumor (MPNST) who were treated at our hospital. Subsequently, the positive immunostaining cell rates were calculated. We also examined the correlation between each immune positive cell rate and age, tissue grade, size, and maximum standardized uptake (SUV-max) values. The 3-year event-free survival (EFS) and overall survival (OS) rates were compared between the positive and negative groups (positive rate >10%; negative <10%) for various immune stains. The positive rates were also compared between the presence and absence of events groups. There was positive staining for the immune checkpoint molecules in every STS type except for PD-1 in MPNST. CD4, CD8, and PD-1 stained lymphocytes in close proximity to the tumor in adjacent tissue sections. A positive correlation was observed between the positive cell rates of each immune component including inflammatory cytokines such as IL-2 and IFN-γ. Additionally, the clinical features positively correlated with the positive PD-1/PD-L1 expression rates. No significant differences in the 3-EFS and OS rates was observed between the PD-1/PD-L1 positive and negative groups. Our results suggest that an inducible immune checkpoint mechanism may be involved in UPS, MFS, and MPNST.
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http://dx.doi.org/10.4081/ejh.2021.3203DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8273625PMC
July 2021

Nontuberculous mycobacterial infection of the knee after arthrocentesis for idiopathic hemarthrosis: A case report.

Ann Med Surg (Lond) 2021 May 16;65:102332. Epub 2021 Apr 16.

Departments of Orthopaedics and Rheumatology, Kindai University Nara Hospital, 1248-1 Otodacho, Ikoma, Nara, 630-0293, Japan.

Introduction: Nontuberculous mycobacterial (NTM) infections of the musculoskeletal system are uncommon. Such infections are typically acquired by direct inoculation after penetrating trauma, surgical procedures, or needle injections. There are no reported cases of NTM infection after arthrocentesis for idiopathic hemarthrosis of the knee. Here we report a case of NTM infection in the knee that developed after arthrocentesis for idiopathic hemarthrosis of the knee.

Presentation Of Case: The patient was an 85-year-old woman who experienced swelling of the left knee. An arthrocentesis was carried out, and hemarthrosis was found. The patient was referred to our hospital for repeated recurrence of hematoma of the knee. Significant swelling was observed in the suprapatellar sac. Magnetic resonance imaging examination revealed a mass at the suprapatellar sac. Laboratory data showed elevation of inflammatory markers. Debridement was performed under arthroscopy and samples were collected for culture. Although routine microbiological cultures were negative, the patient continued to experience knee swelling and laboratory data showed high C-reactive protein levels. Therefore, open debridement was carried out. At 4 weeks after the first surgical treatment, intraoperative cultures yielded . At this point, we diagnosed septic arthritis of the knee due to NTM infection. The patient showed an excellent prognosis with three-drug medical treatment for 1 year.

Conclusion: Clinically, diagnosis of septic arthritis due to NTM infection is not easy. Because selection of examination depends on clinical suspicion, NTM infections should be considered for patients with elevation of inflammatory markers after episodes of surgical procedures, and/or needle injections.
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http://dx.doi.org/10.1016/j.amsu.2021.102332DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8102867PMC
May 2021

Delayed Rupture of All Digital Flexor Tendons Following Volar Locking Plate Fixation for Distal Radius Fracture: A Case Report.

J Hand Surg Asian Pac Vol 2021 Jun;26(2):301-304

Department of Orthopedic Surgery, Katsuragi Hospital, Osaka, Japan.

A 68-year-old man with a right distal radius fracture treated with volar locking plate fixation previously was unable to flex his right thumb and four fingers without experiencing any adverse event. The flexor pollicis longus was reconstructed with a tendon graft using the lengthened flexor digitorum superficialis. The flexor digitorum profundus (FDP) of the ring finger was reconstructed with a tendon graft using the palmaris longus. The FDP of the index and little fingers was reconstructed using the interconnected tendon graft to the ring finger. Postoperatively, active flexion of all fingers and thumb was restored; however, he was unable to grasp thin objects because of the absence of full finger flexion. This is the first case wherein all nine flexor tendons being involved after volar locking plate fixation for a distal radius end fracture. We demonstrated a reconstructive procedure for long-standing multiple flexor tendon rupture after volar locking plate fixation.
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http://dx.doi.org/10.1142/S2424835521720127DOI Listing
June 2021

Treatment Outcomes of Langerhans Cell Histiocytosis: A Retrospective Study.

Medicina (Kaunas) 2021 Apr 7;57(4). Epub 2021 Apr 7.

Department of Orthopedic Surgery, Kindai University Hospital, Osaka-Sayama City, Osaka 589-8511, Japan.

: Langerhans cell histiocytosis (LCH) is a rare disease characterized by the infiltration of one or more organs by Langerhans cell-like dendritic cells. LCH often involves the bone, and its clinical evidence is limited. The purpose of this study is to report on the treatment of LCH at our institution and to add to the evidence for LCH. : We reviewed six cases of LCH treated in our hospital between November 2005 and February 2016. Patient age at the first visit, sex, site of origin, symptoms, image tools used for diagnosis, biopsy site, complications, treatment, and final clinical outcome were evaluated. The median follow-up period was 41 months. : The median patient age at the first visit was 13.5 years. Three male and three female individuals were enrolled. Multiple lesions were observed in five cases, and a solitary lesion was observed in one case. Pain was the chief complaint in five cases. Radiography was the most commonly used imaging tool. Bone scintigraphy or magnetic resonance imaging and positron emission tomography-computed tomography were also used to diagnose systematic LCH. Biopsy of the femur was performed in two cases, and biopsy of the tibia, lumbar vertebrae, rib, and radius was performed in one case each. Regarding comorbidities, one case of hepatitis B and one case of autism were observed. Chemotherapy was initiated in two patients. The other four patients were observed naturally. Continuous disease-free survival was observed in five patients. One patient remained alive but not without disease during the final follow-up examination. : LCH should be diagnosed as early as possible to treat it appropriately.
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http://dx.doi.org/10.3390/medicina57040356DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8067819PMC
April 2021

Lung Adenocarcinoma Presenting as a Soft Tissue Metastasis to the Shoulder: A Case Report.

Medicina (Kaunas) 2021 Feb 20;57(2). Epub 2021 Feb 20.

Department of Orthopedic Surgery, Kindai University Hospital, 377-2 Ohno-Higashi, Osaka-Sayama City, Osaka 589-8511, Japan.

Metastasis to soft tissue is rare, and the pathogenesis remains unclear. Soft tissue metastases (STMs) have varied presentations; existing reports are few. Herein, we report a case of STMs of the shoulder with a rich characterization. A 93-year-old man presented to our hospital with pain and swelling of the left shoulder for one week. Magnetic resonance imaging (MRI) showed a T1 low-intensity and T2 high-intensity mass. We suspected a primary sarcoma and performed a needle biopsy. However, on histopathological examination, the findings were suggestive of lung adenocarcinoma. Fluorine-18 fluorodeoxyglucose (FDG) positron emission tomography-computed tomography also revealed FDG accumulation in the right lung, thus confirming the diagnosis. Oncologists should keep in mind that STMs of lung cancer may resemble soft-tissue sarcomas at the time of initial diagnosis.
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http://dx.doi.org/10.3390/medicina57020181DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7923794PMC
February 2021

Inflammatory Undifferentiated Pleomorphic Sarcoma Mimicking Bacteremia in an Elderly Patient: A Case Report.

Medicina (Kaunas) 2021 Feb 18;57(2). Epub 2021 Feb 18.

Department of Orthopedic Surgery, Kindai University Hospital, Osaka-Sayama City, Osaka 589-8511, Japan.

Undifferentiated pleomorphic sarcoma (UPS) is major type of soft tissue sarcomas. UPS presenting with inflammation is rare, and its pathophysiology remains unclear. Herein, we report a rare case of UPS with prolonged fever. A 91-year-old female complaining of high fever was referred to our hospital because of a high C-reactive protein (CRP) level of 12.51 mg/dL. She had been experiencing intermittent fevers for approximately 10 years. The fever of unknown origin worsened with time and went into remission with repeated antimicrobial therapy. She also had a mass on her central lower back over the sacral region for 6 years, which showed a gradual increase in size. The blood tests showed that the leukocyte count and neutrophils were 6.51 × 10 /µL and 70.3%, respectively. She had a 10 × 10 cm mass on her buttock that showed 2-[fluorine-18] fluoro-2-deoxy-d-glucose (FDG) accumulation on FDG-positron emission tomography-computed tomography examination (standardized uptake value-max value: 5.4). A blood culture examination was performed to rule out bacteremia, however, no bacteria were identified. We then performed a needle biopsy and confirmed the diagnosis of UPS; subsequently, the patient underwent a wide-margin resection. A few days after the surgery, her CRP, leukocyte, and neutrophil levels decreased to 0.305 mg/dL, 2.83 × 10/uL, and 50.1%, respectively. This case demonstrated that UPS with inflammation should be treated surgically as soon as possible after ruling out other sources of infection to achieve a favorable prognosis.
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http://dx.doi.org/10.3390/medicina57020175DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7922332PMC
February 2021

Soft Tissue Myoepithelioma of the Shoulder.

Acta Med Okayama 2020 Dec;74(6):531-535

Department of Orthopedic Surgery, Kindai University Hospital.

Soft tissue myoepitheliomas are often misdiagnosed due to their rarity. Herein, we describe a case of soft tissue myoepithelioma of the shoulder. A 72-year-old woman had a suspected sarcoma on her shoulder and under-went open biopsy. She was referred to our hospital, where the tumor was widely resected and the diagnosis of myoepithelioma was histologically confirmed. No recurrence has been observed in the 3 years since the sur-gery. Careful and prompt planning is necessary for the effective treatment of myoepithelioma.
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http://dx.doi.org/10.18926/AMO/61213DOI Listing
December 2020

Role of Dkk2 in the Muscle/bone Interaction of Androgen-Deficient Mice.

Exp Clin Endocrinol Diabetes 2021 Oct 22;129(10):770-775. Epub 2020 Dec 22.

Department of Physiology and Regenerative Medicine, Kindai University Faculty of Medicine, Osakasayama, Japan.

Androgen deficiency is known to cause both osteoporosis and sarcopenia. Myokines, humoral factors secreted from the skeletal muscles, have recently been getting attention as the key factors related to the interactions between muscle and bone. Dickkopf (Dkk) 2 is known as an inhibitor of canonical Wnt/β-catenin signaling, and Wnt/β-catenin signaling is crucial for the maintenance of muscle and bone. The present study was therefore performed to investigate the roles of Dkk2 in the alterations of muscle and bone of androgen-deficient mice with orchidectomy (ORX). ORX significantly enhanced Dkk2 mRNA levels, but not other Dkks and secreted frizzled related proteins, in the soleus muscles of mice. Moreover, ORX enhanced serum Dkk2 levels, but not Dkk2 mRNA levels in the tibial bone tissues, the white adipose tissues and liver of mice. In simple regression analyses, serum Dkk2 levels were negatively related to trabecular bone mineral density at the tibias in mice employed in the experiments. experiments, testosterone suppressed Dkk2 mRNA levels in mouse muscle C2C12 cells. In conclusion, we showed that androgen deficiency enhances Dkk2 expression and secretion in the muscles of mice. Dkk2 might be involved in androgen deficiency-induced muscle wasting and osteopenia as a myokine linking muscle to bone.
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http://dx.doi.org/10.1055/a-1331-7021DOI Listing
October 2021

Radiation-Induced Osteosarcoma in the Cervical Spine after Definitive Radiotherapy for Esophageal Cancer: A Case Report.

Spine Surg Relat Res 2020 28;4(4):374-376. Epub 2020 May 28.

Department of Orthopaedic Surgery, Kindai University Hospital, Sayama, Japan.

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http://dx.doi.org/10.22603/ssrr.2019-0127DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7661033PMC
May 2020

Referencing the substitute anteroposterior line of the tibia improves rotational alignment of the tibial component in medial unicompartmental knee arthroplasty.

Knee 2020 Oct 22;27(5):1458-1466. Epub 2020 Aug 22.

Department of Orthopaedic Surgery, Kindai University Hospital, 377-2 Ohno-Higashi, Osaka-Sayama City, Osaka 589-8511, Japan; Department of Orthopaedic Surgery, Kindai University Nara Hospital, 1248-1 Otoda-cho, Ikoma City, Nara Prefecture 630-0293, Japan.

Background: There is no consensus regarding how best to determine the tibial rotational alignment in unicompartmental knee arthroplasty (UKA). The purpose of this study was to clarify whether using the substitute anteroposterior (sAP) line of the tibia, as has recently been proposed, can improve tibial rotation.

Methods: The study included 57 consecutive medial UKAs. From May 2015 to September 2016, 28 knees in 28 patients underwent UKA using the medial intercondylar ridge (MIR) line as the tibial anteroposterior (AP) reference (MIR group). From October 2016 to March 2018, 29 knees in 29 patients underwent UKA using the sAP line (sAP group). In both groups, the external rotation angle of the tibial component relative to a line perpendicular to the surgical epicondylar axis was measured using computed tomography-based three-dimensional preoperative planning software for TKA and UKA.

Results: The mean external rotation angles of the tibial component in the MIR and sAP groups were 5.2° ± 8.5° (range, -12.4° to 20.8°) and 0.7° ± 3.2° (range, -6.0° to 7.4°), respectively (unpaired t test, P = 0.014). The variation in the external rotation angle of the tibial component was significantly smaller in the sAP group than in the MIR group (F test, P < 0.0001), as was the number of the outliers with more than ±5° error (Fisher's exact test, P < 0.0001).

Conclusions: The use of the sAP line as the AP reference could improve and stabilize the rotational orientation of the tibial component in UKA procedures.
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http://dx.doi.org/10.1016/j.knee.2020.07.086DOI Listing
October 2020

Characterization of PD-1/PD-L1 Immune Checkpoint Expression in Osteosarcoma.

Diagnostics (Basel) 2020 Jul 29;10(8). Epub 2020 Jul 29.

Department of Orthopedic Surgery, Kindai University Hospital, 377-2 Ohno-Higashi, Osaka-Sayama City, Osaka 589-8511, Japan.

Recent data have suggested that PD-1 and PD-L1 are involved in osteosarcoma (OS) pathogenesis; however, their contributions are not well-established. Here, the PD-1/PD-L1 expression was evaluated in (OS) cases. Preoperative needle biopsy specimens were obtained from 16 patients with OS. Immunostaining for CD4, CD8, PD-1, and PD-L1 was performed on pathological specimens. Clinical parameters, including age, tumor size, preoperative alkaline phosphatase (ALP) level, standardized uptake value (SUV)-max level, and survival rate, were compared between PD-1/PD-L1-positive and -negative groups. CD4-, CD8-, PD-1-, and PD-L1-positive rates among all specimens were 75%, 75%, 18.7%, and 62.5%, respectively. The rates of co-expression of CD4 and CD8 with PD-L1 were 56.2% and 50%, respectively. Tumors were significantly larger in PD-L1-negative cases than in PD-L1-positive cases. Age, size and ALP and SUV-max levels did not differ significantly between PD-1/PD-L1-positive and -negative cases. The 3-year survival rates did not differ significantly between PD-1-positive and -negative cases or between PD-L1-positive and -negative cases. However, the occurrence of cancer-related events, including recurrence, metastasis, and death was associated with the PD-1-negative and PD-L1-positive status. The PD-1/PD-L1 checkpoint is likely involved in the immune microenvironment in OS and may be involved in the occurrence of cancer-related events.
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http://dx.doi.org/10.3390/diagnostics10080528DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7459780PMC
July 2020

Salmonella Osteomyelitis of the Rib Mimicking a Mammary Tumor: A Case Report.

Tohoku J Exp Med 2020 08;251(4):273-277

Department of Orthopedic Surgery, Kindai University Hospital.

Salmonella infection predominantly causes four clinical syndromes: enteric fever, gastroenteritis, bacteremia, and asymptomatic carrier state. Salmonella osteomyelitis is an extremely rare manifestation of salmonella infection except in children with hemoglobinopathies. Salmonella osteomyelitis has been reported to mostly affect the diaphysis of long bones and lumbar spine. Here, we describe a case of salmonella osteomyelitis of the right 6th rib in a 74-year-old woman who presented with breast pain, swelling, high fever and local heat. Her medical history showed myocardial infarction; namely, at the age of 71, the patient had undergone the drug-eluting stent placement in the left anterior descending artery. A computed tomography (CT) scan at the first visit to another hospital showed a mass in the chest that invaded the ribs. F-fluorodeoxyglucose-positron emission tomography-computed tomography imaging showed a lesion suspected to be a mammary malignant tumor. A needle biopsy revealed mesenchymal cells and suspected mammary sarcoma. However, the osteomyelitis of the rib was diagnosed when pyogenic tissue was observed during an open biopsy. The bacterial culture examination identified Salmonella enterica. Surgical drainage and antibiotic treatment were performed. Importantly, there was no evidence for any underlying disease that could lead to an immunocompromised status of the patient. To our knowledge, this is the first report of salmonella osteomyelitis of the rib presenting in an older female that required differentiation from a mammary tumor. Clinicians should consider rib osteomyelitis when they find swelling and local heat in the female's breast tissue and detect no cancerous tissue.
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http://dx.doi.org/10.1620/tjem.251.273DOI Listing
August 2020

Ascorbate sensitizes human osteosarcoma cells to the cytostatic effects of cisplatin.

Pharmacol Res Perspect 2020 08;8(4):e00632

Graduate School of Medical Sciences, Faculty of Medicine, Kindai University, Osaka, Japan.

Osteosarcoma (OS) is the most common malignant bone tumor and a leading cause of cancer-related deaths in children and adolescents. Current standard treatments for OS are a combination of preoperative chemotherapy, surgical resection, and adjuvant chemotherapy. Cisplatin is used as the standard chemotherapeutic for OS treatment, but it induces various adverse effects, limiting its clinical application. Improving treatment efficacy without increasing the cisplatin dosage is desirable. In the present study, we assessed the combined effect of ascorbate on cisplatin treatment using cultured human OS cells. Co-treatment with ascorbate induced greater suppression of OS cell but not nonmalignant cell proliferation. The chemosensitizing effect of ascorbate on cisplatin treatment was tightly linked to ROS production. Altered cellular redox state due to increased ROS production modified glycolysis and mitochondrial function in OS cells. In addition, OS cell sphere formation was markedly decreased, suggesting that ascorbate increased the treatment efficacy of cisplatin against stem-like cells in the cancer cell population. We also found that enhanced MYC signaling, ribosomal biogenesis, glycolysis, and mitochondrial respiration are key signatures in OS cells with cisplatin resistance. Furthermore, cisplatin resistance was reversed by ascorbate. Taken together, our findings provide a rationale for combining cisplatin with ascorbate in therapeutic strategies against OS.
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http://dx.doi.org/10.1002/prp2.632DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7387887PMC
August 2020

The role of oxidation of low-density lipids in pathogenesis of osteoarthritis: A narrative review.

J Int Med Res 2020 Jun;48(6):300060520931609

Department of Orthopaedic Surgery, Kindai University Hospital, Osaka-Sayama City, Osaka, Japan.

Osteoarthritis (OA) is a chronic joint disorder that causes degeneration of cartilage, synovial inflammation, and formation of osteophytes. Aging, obesity, and sex are considered the main risk factors of OA. Recent studies have suggested that metabolic syndrome (MetS) disorders, such as hypertension, hyperlipidemia, diabetes mellitus, and obesity, may be involved in the pathogenesis and progression of OA. MetS disorders are common diseases that also result in atherosclerosis. Researchers believe that OA and atherosclerosis have underlying similar molecular mechanisms because the prevalence of both diseases increases with age. Oxidation of low-density lipoprotein (ox-LDL) is believed to play a role in the pathogenesis of atherosclerosis. Recent reports have shown that ox-LDL and low-density lipoprotein receptor 1 (LOX-1) are involved in the pathogenesis of OA. The purpose of this narrative review is to summarize the current understanding of the role of the LOX-1/ox-LDL system in the pathogenesis of OA and to reveal common underlying molecular pathways that are shared by MetS in OA and the LOX-1/ox-LDL system.
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http://dx.doi.org/10.1177/0300060520931609DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7303502PMC
June 2020
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