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Akihiko Takeuchi - Top 30 Publications

Mid- to long-term clinical outcome of giant cell tumor of bone treated with calcium phosphate cement following thorough curettage and phenolization.

Giant cell tumors of bone (GCTB) are intermediate and locally aggressive bone tumor. Calcium phosphate cement (CPC) is a bone void filler used in orthopaedic surgery. This study investigated the clinical outcome of GCTB treated with thorough curettage, phenolization, and CPC.

The Efficacy of Wide Resection for Musculoskeletal Metastatic Lesions of Renal Cell Carcinoma.

This study evaluated the outcome of wide resection for metastatic renal cell carcinoma (RCC) to the bone or soft tissue.

Risk factors for postoperative deep infection in bone tumors.

Postoperative deep infection after bone tumor surgery remains a serious complication. Although there are numerous reports about risk factors for postoperative deep infection in general surgery, there is only a small number of reports about those for bone tumor surgery. This retrospective study aimed to identify risk factors for postoperative deep infection after bone tumor resection.

Knee joint preservation surgery in osteosarcoma using tumour-bearing bone treated with liquid nitrogen.

To preserve the joint structure in order to maintain good limb function in patients with osteosarcoma, we perform epiphyseal or metaphyseal osteotomy and reconstruction using frozen autografts that contain a tumour treated with liquid nitrogen. There are two methods of using liquid nitrogen-treated autografts: the free-freezing method and the pedicle-freezing method. The purpose of this study was to evaluate the results of intentional joint-preserving reconstruction using the free-freezing method and the pedicle-freezing method in patients with osteosarcoma.

An unusual case of proximal humeral simple bone cyst in an adult from secondary cystic change.

Simple bone cysts (SBC) have been documented to occur in adults with closed physeal plates, most commonly affecting the calcaneus in this patient subset. Although most authors theorize an association to trauma, etiology of simple bone cysts remains an enigma up to now.

Giant cell tumor of the thoracic spine completely removed by total spondylectomy after neoadjuvant denosumab therapy.

Denosumab, a novel monoclonal antibody that targets the receptor activator of nuclear factor-κB (RANK) ligand (RANKL), has recently been used to treat patients with giant cell tumor of bone (GCTB). However, few reports have described the clinical results of denosumab therapy for spinal GCTB and evaluated treatment efficacy with respect to the entirety of the resected vertebra after denosumab therapy.

Intercalary frozen autograft for reconstruction of malignant bone and soft tissue tumours.

In 1999, we developed a technique using frozen autografts-tumour-containing bone treated with liquid nitrogen-for the reconstruction of malignant bone tumours. The purpose of this study was to evaluate the functional and oncological outcomes of frozen autografts for intercalary reconstruction of malignant bones and soft tissue tumours.

Phase 1/2 study of immunotherapy with dendritic cells pulsed with autologous tumor lysate in patients with refractory bone and soft tissue sarcoma.

There are limited options for the curative treatment of refractory bone and soft tissue sarcomas. The purpose of this phase 1/2 study was to assess the immunological and clinical effects of dendritic cells (DCs) pulsed with autologous tumor lysate (TL) in patients with advanced bone and soft tissue sarcomas.

Pathogenesis of Osteosclerotic Change Following Treatment with an Antibody Against RANKL for Giant Cell Tumour of the Bone.

Giant cell tumours (GCTs) of the bone are intermediate tumours that are locally aggressive. Denosumab, an antibody against receptor activator of nuclear factor kappa-B ligand (RANKL), was recently developed; however, it induces osteosclerotic change through an unknown mechanism. We determined whether osteosclerotic change could be induced by neoplastic stromal cells of giant cell tumours (GCTs).

Do Mesenchymal Stem Cells Derived From Atypical Lipomatous Tumors Have Greater Differentiation Potency Than Cells From Normal Adipose Tissues?

The p53 protein in mesenchymal stem cells (MSCs) regulates differentiation to osteogenic or adipogenic lineage. Because p53 function is depressed in most malignancies, if MSCs in malignancy also have p53 hypofunction, differentiation therapy to osteogenic or adipogenic lineage may be an effective treatment. We therefore wished to begin to explore this idea by evaluating atypical lipomatous tumor/well-differentiated liposarcoma (ALT/WDL) cells, because murine double minute 2 (MDM2) gene amplification, which leads to p53 hypofunction, is found in almost all ALT/WDLs.

Functional and radiological outcomes of a minimally invasive surgical approach to monostotic fibrous dysplasia.

Reports showing high recurrence rates for intralesional curettage and bone grafting have made the current treatment principle for fibrous dysplasia controversial. This study aimed to report the postoperative clinical outcomes from three minimally invasive surgical strategies we use for monostotic fibrous dysplasia (MFD).

Surgical management of proximal fibular tumors: A report of 12 cases.

Aggressive benign or malignant tumors in the proximal fibula may require en bloc resection of the fibular head, including the peroneal nerve and lateral collateral ligament. Here, we report the treatment outcomes of 12 patients with aggressive benign or malignant proximal fibula tumors.

A case of infected schwannoma mimicking malignant tumor.

Infected schwannoma has been reported, this being one of the four cases published in the literature. Infected schwannoma has proven to be a tough diagnostic challenge to the treating tumor surgeon, mimicking infectious entities and most essentially, a malignant tumor.

Clinical Outcome of Reconstruction Using Frozen Autograft for a Humeral Bone Tumor.

We developed a frozen autograft technique in which a tumor-bearing bone was treated with liquid nitrogen for reconstruction. The purpose of this study was to evaluate the functional outcomes of this technique after resection of humeral bone tumors.

Efficacy of glycogen synthase kinase-3β targeting against osteosarcoma via activation of β-catenin.

Development of innovative more effective therapy is required for refractory osteosarcoma patients. We previously established that glycogen synthase kinase-3β (GSK- 3β) is a therapeutic target in various cancer types. In the present study, we explored the therapeutic efficacy of GSK-3β inhibition against osteosarcoma and the underlying molecular mechanisms in an orthotopic mouse model. Expression and phosphorylation of GSK-3β in osteosarcoma and normal osteoblast cell lines was examined, together with efficacy of GSK-3β inhibition on cell survival, proliferation and apoptosis and on the growth of orthotopically-transplanted human osteosarcoma in nude mice. We also investigated changes in expression, phosphorylation and co-transcriptional activity of β-catenin in osteosarcoma cells following GSK-3β inhibition. Expression of the active form of GSK- 3β (tyrosine 216-phosphorylated) was higher in osteosarcoma than osteoblast cells. Inhibition of GSK-3β activity by pharmacological inhibitors or of its expression by RNA interference suppressed proliferation of osteosarcoma cells and induced apoptosis. Treatment with GSK-3β-specific inhibitors attenuated the growth of orthotopic osteosaroma in mice. Inhibition of GSK-3β reduced phosphorylation at GSK- 3β-phospho-acceptor sites in β-catenin and increased β-catenin expression, nuclear localization and co-transcriptional activity. These results suggest the efficacy of GSK-3β inhibitors is associated with activation of β-catenin, a putative tumor suppressor in bone and soft tissue sarcoma and an important component of osteogenesis. Our study thereby demonstrates a critical role for GSK-3β in sustaining survival and proliferation of osteosarcoma cells, and identifies this kinase as a potential therapeutic target against osteosarcoma.

Experience of total scapular excision for musculoskeletal tumor and reconstruction in eastern Asian countries.

Total scapulectomy and reconstruction has been performed for scapular tumor, however, most of the reconstruction methods have resulted in poor functional outcomes and there is still room for improvement. Most of the reports of reconstruction after scapulectomy are from a single institution. In the present study, we investigated functional outcomes after total scapulectomy in a multicenter study in The Eastern Asian Musculoskeletal Oncology Group (EAMOG). Thirty-three patients who underwent total scapulectomy were registered at EAMOG affiliated hospitals. The patients were separated into no reconstruction group (n=8), humeral suspension group (n=15) and prosthesis group (n=10). Functional outcome was assessed by the Enneking score. One-way ANOVA was used to compare parameters between the patient groups. Complications included five local recurrences, one superficial infection, one dislocation and one clavicle protrusion. The average follow-up period was 43.5  months. The average active flexion range was 45.8° (0-120°), and 37.1° in abduction (0-120°). The mean total functional score was 22.9 out of 30 (15-29), which is a satisfactory score following resection of the shoulder girdle. There were significant differences in reconstruction methods for active range of motion. Bony reconstruction provided better range of motion in this study. There was a variety of reconstruction methods after scapulectomy in the eastern Asian countries. Although better functional score was obtained using scapular prosthesis or recycled bone and prosthesis composite grafting, postoperative function is still lower than preoperative function. Modified designed prosthesis with or without combination of recycle bone or allograft would restore the lost shoulder function in the future.

Non-toxic Efficacy of the Combination of Caffeine and Valproic Acid on Human Osteosarcoma Cells In Vitro and in Orthotopic Nude-mouse Models.

We have previously reported that caffeine can enhance chemotherapy efficacy of bone and soft-tissue sarcoma via cell-cycle perturbation. Valproic acid has histone deacetylase (HDAC) inhibitory activity. The present study aimed to investigate the efficacy of the combination of valproic acid and caffeine on human osteosarcoma cells in vitro and in orthotopic nude-mouse models.

Clinical outcome of recurrent giant cell tumor of the extremity in the era before molecular target therapy: the Japanese Musculoskeletal Oncology Group study.

Giant cell tumor of the bone (GCTB) is classified as an intermediate, locally aggressive but rarely metastasizing tumor. The mainstay of treatment for the treatment of GCTB had been the surgical removal until an anti- receptor activator of nuclear factor-kappa B ligands (RANKL) antibody denosumab was developed. And favorable responses and the possibility of surgical downstaging have been reported. However, the long-term outcome of denosumab has not yet been confirmed and moreover the long-term clinical outcome after the recurrence of GCTB in the era before molecular target therapy is still uncertain. The aim of this study was to evaluate the long-term clinical outcome of recurrent GCTB of the extremity in the era before molecular target therapy and to determine the factors that affect the repetitive recurrence and sacrifice of adjacent joints.

Clinical relevance of peroxisome proliferator-activated receptor-gamma expression in myxoid liposarcoma.

Peroxisome proliferator-activated receptor gamma (PPARγ) is a ligand-activated transcription factor that belongs to the nuclear hormone receptor superfamily. PPARγ is essential in adipocyte differentiation from precursor cells. Its antitumorigenic effects are reported in certain malignancies; however, its effects in liposarcoma are unclear.

Balancing Prolonged Survival with QoL Using Low-dose Pazopanib Maintenance: A Comparison with the PALETTE Study.

A consensus has not been reached regarding the optimal pazopanib dosing schedule, which we determined in patients who received pazopanib at our Institution.

The outcomes of reconstruction using frozen autograft combined with iodine-coated implants for malignant bone tumors: compared with non-coated implants.

We perform reconstruction using frozen tumor bone treated by liquid nitrogen after excision of malignant bone tumors. To prevent post-operative infection, we use iodine-coated implants that we developed. The purpose of this study is to compare the outcome of reconstruction using frozen autograft with non-coated implants (group N) and iodine-coated implants (group I).

Radiological assessment of the femoral bowing in Japanese population.

Differences in the magnitude of bowing between races are well-known characteristics of the femur. Asian races have an increased magnitude of femoral bowing but most of the orthopedic implants designed for the femur do not match this exaggerated bowing. We calculated the sagittal and coronal femoral bowing in the Japanese population at different levels of the femur and addressed its surgical significance.

Tenosynovial giant cell tumors in unusual locations detected by positron emission tomography imaging confused with malignant tumors: report of two cases.

A tenosynovial giant cell tumor (T-GCT) is a benign synovial tumor arising from the synovium, bursae, or tendon sheath. It can be intra- or extra-articular and localized or diffuse. Diffuse T-GCT is considered as a locally aggressive. Positron emission tomography (PET) with fluorine-18 fluorodeoxyglucose with computed tomography (FDG PET/CT) is widely used to differentiate malignant from benign tumors and to detect distant metastasis. However, FDG PET/CT is limited by false-positive findings. In this study, we present two cases of T-GCT that developed in unusual locations and were confused with malignant tumors. The final diagnoses were histologically confirmed as T-GCTs.

The linea aspera as a guide for femoral rotation after tumor resection: is it directly posterior? A technical note.

The linea aspera is the rough, longitudinal crest on the posterior surface of the femoral shaft. Most orthopedic surgeons depend on the linea aspera as an intraoperative landmark identifying the true posterior aspect of the femur. We investigated the position of the linea aspera to verify whether the surgeon can rely on this accepted belief.

Symptomatic small schwannoma is a risk factor for surgical complications and correlates with difficulty of enucleation.

Postoperative neurological deficits of schwannomas are the complications that we want to avoid most. Predicting postoperative neurological deficits is crucial; however, the correlation between preoperative symptoms and neurological findings with postoperative neurological complications has not yet been completely clarified. Here we analyzed the risk factors for postoperative neurological complications. The study included 131 tumors from 107 patients histologically confirmed as schwannomas, which developed in the extremities and trunk without spinal cord involvement. The correlation between clinical findings and postoperative complications were statistically analyzed. One-hundred three tumors (78.6 %) had the preoperative neurological symptoms; these symptoms were detected in 93.3 % of small tumors (<4 cm(3)). We defined it as follows about the anatomical location of schwannomas. One is "central type" that normal nerve bundles widely splayed over the tumor's capsule (tumor located in the central region of the nerve). Another is "peripheral type" that easy to enucleate without neurolysis (tumor located in the peripheral region of the nerve). Static analysis showed a significant difference in the Tinel sign, numbness, and postoperative neurological deficits (p = 0.04, 0.006, p < 0.001, respectively). Twenty-one cases (16.0 %) showed new postoperative neurological symptoms, including numbness in 12 cases, dysesthesia in three cases, pain in three cases, and slight motor palsy in two cases. In statistical analysis, small tumors (<4 cm(3)) significantly correlated with Tinel sign (p < 0.001), and was marginally significant with postoperative neurological deficits (p = 0.05). Moreover, small tumors (<4 cm(3)) accompanying numbness preoperatively significantly correlated with postoperative neurological deficits (p = 0.04). Small (<4 cm(3)) tumors significantly correlated with the preoperative neurological symptoms. Those tumors accompanying numbness also significantly correlated with the difficulty of the enucleation and postoperative neurological deficits. These findings will help to predict the neurological complication.

Ten-Year Follow-Up of Desarthrodesis of the Knee Joint 41 Years after Original Arthrodesis for a Bone Tumor.

Introduction. The main indication for knee arthrodesis in tumor surgery is a tumor that requires an extensive resection in which the joint surface cannot be preserved. We report a patient that had knee desarthrodesis 41 years after giant cell tumor resection followed by a knee arthrodesis. This is the longest reported follow-up after desarthrodesis and conversion to total knee arthroplasty (TKA), almost ten years. Case Report. A 71-year-old man with a distal femoral giant cell tumor had undergone a resection of the distal femur and knee arthrodesis using Kuntscher nail in 1962. In July 2003 he experienced gradually increasing pain of his left knee. We performed a desarthrodesis and conversion to TKA in 2005. The postoperative period passed uneventfully as his pain and gait improved, with gradually increasing range of motion (ROM) and no infection. He now walks independently, with no brace or contractures. Conclusion. Desarthrodesis of the knee joint and conversion to TKA are a difficult surgical choice with a high complication risk. However, our patient's life style has improved, he has no pain, and he can ascend and descend stairs more easily. The surgeon has to be very meticulous in selecting a patient for knee arthrodesis and counseling them to realize that their expectations may not be achievable.

Successful correction of tibial bone deformity through multiple surgical procedures, liquid nitrogen-pretreated bone tumor autograft, three-dimensional external fixation, and internal fixation in a patient with primary osteosarcoma: a case report.

In a previous report, we described a method of reconstruction using tumor-bearing autograft treated by liquid nitrogen for malignant bone tumor. Here we present the first case of bone deformity correction following a tumor-bearing frozen autograft via three-dimensional computerized reconstruction after multiple surgeries.

Frozen Autograft-Prosthesis Composite Reconstruction in Malignant Bone Tumors.

Several methods are available using an endoprosthesis or biological reconstruction for malignant bone tumors. Methods that use allograft-prosthesis composites have shown promising results. In 1999, the authors developed a method of reconstruction that uses a tumor-bearing autograft treated with liquid nitrogen. This technique was modified to produce a pedicle frozen autograft to maintain anatomical continuity on one side. In this study, the results of bone reconstructions using frozen autograft-prosthesis composites were retrospectively evaluated. The demographic data, histological records, surgical procedures, functional scores, and complications of 22 patients who had bone sarcoma or metastasis and at least 2 years of follow-up were reviewed. There were 19 patients with primary bone sarcoma and 3 with bone metastasis. Average age was 36 years (range, 9-73 years), and mean follow-up was 63 months (range, 24-176 months). Reconstructions were performed on 10 proximal femurs, 5 distal femurs, 4 proximal tibias, 1 proximal humerus, 1 proximal radius, and 1 hemipelvis. There were 12 pedicle-freezing and 10 free-freezing procedures. Union rate was 90% (9/10), and average union time was 9.5 months. Average Musculoskeletal Tumor Society score was 89.3%. Complications included 1 fracture, 2 infections, 3 soft tissue recurrences, and 1 posterior interosseous nerve palsy. The authors concluded that the frozen autograft-prosthesis composite demonstrated excellent Musculoskeletal Tumor Society scores, a low complication rate, and a good union rate and was superior when used with the pedicle-freezing technique.

Treatment of a Simple Bone Cyst Using a Cannulated Hydroxyapatite Pin.

Simple bone cysts (SBCs) are benign bone tumors. However, the treatment of SBCs remains controversial because of their healing rate and the invasiveness of surgery. The purpose of the present study was to evaluate the treatment of SBCs using a cannulated hydroxyapatite (HA) pin.A total of 43 patients (35 males, 8 females; mean age 12.1 years; age range, 5-22 years) with SBCs were treated with continuous decompression by inserting ceramic HA pins between 1989 and 2014. The SBCs were located in the calcaneus in 23, the humerus in 15, the femur in 3, and the pelvis in 2 cases. In all patients, minimal fenestration of the cyst wall and curettage and multiple drilling in the cyst wall were performed, followed by insertion of the HA pin. The mean follow-up period was 26.6 months. Operating time, healing period, risk factors for recurrence, and the cure rate were evaluated.Healing was achieved without intervention in 38 patients after a mean of 6.4 months. Two patients had persistent small residual cysts, which had no changes after 1 year at the latest follow-up. There were 5 patients with recurrences (humerus 4, femur 1), who were cured by curettage and artificial bone grafting. The final healing rate by cannulation only using an HA pin was 88.2%. On Fisher exact test, age, site of SBCs, and distance from the physis were found to be significantly associated with SBC recurrence (P < 0.05).In the present study, cannulation using an HA pin for SBCs was found to be a useful technique, particularly for calcaneal cysts, because it is a minimally invasive procedure with a high cure rate. In patients <10 years, involvement of the humerus and contact with the growth plate were significant risk factors for SBC recurrence.

Salvage method for unplanned excision of soft tissue sarcoma: long-term results of second-look surgery following radio-hyperthermo-chemotherapy.

We have established a "second-look operation" protocol that consists of whole biopsy of surgical scar tissue following radio-hyperthermo-chemotherapy (RHC) after unplanned excision of soft tissue sarcoma. Out of 30 patients who underwent RHC for soft tissue sarcoma at our Institution, 6 were enrolled into this study to undergo a second-look operation for unplanned excision. Radiotherapy was given to a total dose of 32 Gy. Hyperthermia was conducted once a week, for a total of five sessions. Chemotherapy was performed at weekly intervals. Surgery was performed to excise the scar tissue that was enhanced on preoperative MRI. In all six cases, no residual tumors were identified in resected scar tissue; thus, no additional wide excision was performed. The average follow-up period was 10.9 years. There were no local recurrences, and all patients were alive at their final follow-up. Long-term follow-up confirmed that RHC can replace additional wide excision for unplanned excision of soft tissue sarcoma.