Makoto Ieguchi

SYT-SSX breakpoint peptide vaccines in patients with synovial sarcoma: A study from the Japanese Musculoskeletal Oncology Group†

In the present study, we evaluated the safety and effectiveness of SYT‐SSX‐derived peptide vaccines in patients with advanced synovial sarcoma. A 9‐mer peptide spanning the SYT‐SSX fusion region (B peptide) and its HLA‐A*2402 anchor substitute (K9I) were synthesized. In Protocols A1 and A2, vaccines with peptide alone were administered subcutaneously six times at 14‐day intervals. The B peptide was used in Protocol A1, whereas the K9I peptide was used in Protocol A2. In Protocols B1 and B2, the peptide was mixed with incomplete Freunds adjuvant and then administered subcutaneously six times at 14‐day intervals. In addition, interferon‐α was injected subcutaneously on the same day and again 3 days after the vaccination. The B peptide and K9I peptide were used in Protocols B1 and B2, respectively. In total, 21 patients (12 men, nine women; mean age 43.6 years) were enrolled in the present study. Each patient had multiple metastatic lesions of the lung. Thirteen patients completed the six‐injection vaccination schedule. One patient developed intracerebral hemorrhage after the second vaccination. Delayed‐type hypersensitivity skin tests were negative in all patients. Nine patients showed a greater than twofold increase in the frequency of CTLs in tetramer analysis. Recognized disease progression occurred in all but one of the nine patients in Protocols A1 and A2. In contrast, half the 12 patients had stable disease during the vaccination period in Protocols B1 and B2. Of note, one patient showed transient shrinkage of a metastatic lesion. The response of the patients to the B protocols is encouraging and warrants further investigation.

Clinical Problems After Initial Unplanned Resection of Sarcoma

OBJECTIVE Unplanned resection of a sarcoma is often chosen in the early phase by general physicians without any imaging scrutiny. The present study aimed to highlight the clinical problems associated with unplanned resection of sarcomas. METHODS Thirty-eight patients who underwent unplanned resection of a sarcoma and additional treatment were examined. The definite histological grading was high in 31 patients and low in 7 patients. RESULTS The tumors were located in the depth of the subfascia in 13 patients. The maximal tumor sizes exceeded 5 cm in 16 patients. Preoperative MRI was only performed in six patients. The previous surgical margins were intralesional in 20 patients and marginal in 18 patients. Inappropriate transverse skin incisions were found in 21 patients. Extensive hematoma at the initial surgical site was seen in five patients. Thirty-three patients accepted additional wide resection due to the insufficient removal of malignancy. During an average follow-up of 42.7 months, seven patients died of lung and brain metastases. CONCLUSIONS On excision of any soft tissue tumor, surgeons should be aware of the potential risk for erroneous management of malignancy. If not, careless surgery may render the treatment protocol complicated and require excessive additional tissue resection with poor function and prognosis. Appropriate salvage treatment may have a significant role to play after unplanned resection of the sarcoma.

Role of FDG-PET/CT for monitoring soft tissue tumors

The aim of the current study was to evaluate the limitations of 2-deoxy-2-F18-fluoro-D-glucose positron emission tomography combined with computed tomography (FDG-PET/CT) when monitoring soft tissue tumors. The diagnostic criteria of malignancy was defined as the tumor having a maximum standardized uptake value (SUVmax) ≥2.0 and a maximum diameter ≥5 cm as measured using FDG-PET/CT. One-hundred-and-thirteen patients, that were either included in the criteria or not, were compared. In addition, the values of SUVmax of the primary tumor and relapse in 12 patients were evaluated. The Kaplan-Meier analysis demonstrated that patients with tumors measuring ≥5 cm size and ≥2.0 SUVmax were associated with a worse survival rate. Among the 12 patients with relapse, statistical significances were detected in the tumor diameters, however, not in the SUVmax values. Thus, the criteria identified patients that were associated with a poor prognosis, and the SUVmax of distant metastases and local recurrences were identified to be significantly affected by tumor size.

Reconstruction of bone defects using rhBMP-2-coated devitalized bone.

Massive bone defects often are caused by radical resection of bone tumors. Reconstruction of the defect by reimplantation of the resected bone segment after it has been devitalized is advantageous because of its ability to match the size of the defect. In addition, this technique carries a low risk for local recurrence of the tumor, avoids immunologic reaction, and is low in cost. However, limited osteogenic potential of the devitalized bone often leads to delayed union, gradual resorption, and mechanical weakness of the reimplanted segment. We applied rhBMP-2 in a biodegradable polymer delivery system to the devitalized bone. Middiaphyseal bone defects were created by resection in rat femurs. The resected segments were autoclaved at 135°C for 15 minutes, coated with a rhBMP-2-retaining paste on the outer surface, and then reimplanted into the defects. In a brief time, newly formed bone was seen on the surface of the devitalized bone. After 12 weeks, a solid bone mass encasing the dead bone segments was consistently formed and abundant new bone formation was visible in the segments as they were remodeled. The amount of new bone formed could be regulated by the amount of the rhBMP-2-retaining paste applied to the bone segments. This method presents a new approach for the reconstruction of bone defects.

Pleomorphic malignant fibrous histiocytoma: response of bone, lung, and brain metastases to chemotherapy

We present a case of pleomorphic malignant fibrous histiocytoma arising from the left forearm in a 45-year-old man who had undergone resection and radiotherapy for a tumor 3 years previously. At his first visit, he had multiple lung and bone metastases. Although these metastases responded well to systemic chemotherapy, brain metastases newly appeared and caused the death of the patient. These findings demonstrate that individual sarcomatous metastatic organs exhibit different sensitivities to chemotherapy. The mechanism of this phenomenon is discussed with a review of previous reports. It is suggested that the blood-brain barrier may play an important role in sensitivity to chemotherapy.

A case report of surgical debulking for a huge mass of elephantiasis neuromatosa.

Achievement of a safe outcome for an extensive mass with hypervascularity in the extremities requires a surgical team skilled in musculoskeletal oncology. We report debulking surgery for a huge mass of elephantiasis neuromatosa in the right leg of a 56-year old man using the novel Ligasure® vessel sealing system.

An unusual presentation of pneumothorax associated with cystic lung metastasis from epithelioid sarcoma: A case report and review of the literature

Circumscribed solid nodules are common in pulmonary metastases from sarcoma, but cystic pulmonary metastases from sarcomas are extremely rare. An unusual case of a 33-year-old man presenting with left spontaneous pneumothorax in association with cystic pulmonary metastases from an epithelioid sarcoma in the left forearm was discussed in the present study. The patient underwent wide resection of an epithelioid sarcoma in the left forearm 6 years prior. Periodical computed tomography revealed a gradual increase in the number and size of bilateral multiple cystic pulmonary metastases despite repeated chemotherapy treatment. At 33 years of age, the patient visited the outpatient department for sudden left chest pain and dyspnea. Plain radiography demonstrated spontaneous pneumothorax in the left lung; chest tube insertion and pleurodesis were successfully performed thereafter. At the last follow-up, 24 months after spontaneous pneumothorax, he is still alive and receiving chemotherapy treatment. Spontaneous pneumothorax is a common complication associated with cystic pulmonary metastases from epithelioid sarcoma. Orthopedic oncologists need to be aware of this unusual sarcomatous metastasis during the follow-up of advanced epithelioid sarcoma.

Lymphoproliferative disorder with pathological fracture of the femur in a patient with rheumatoid arthritis treated with methotrexate: A case report

Methotrexate (MTX) is the key drug for the treatment of rheumatoid arthritis (RA). MTX-treated RA has been associated with the development of lymphoproliferative disorders (LPDs). Notably, the hyperimmune state of RA itself or the immunosuppressive state induced by MTX administration may contribute to development of LPD. Furthermore, Epstein-Barr virus (EBV) has been indicated to contribute to the development of MTX-LPD. MTX-associated LPD (MTX-LPD) may affect nodal or extranodal sites, including the gastrointestinal tract, skin, lungs, kidneys, and soft tissues, at an almost equal frequency. However, it is rare for MTX-LPD to manifest as multiple bone tumors with a pathological fracture. The present study reported the case of a 46-year-old Japanese woman with RA who had complications of EBV-positive MTX-LPD during an approximate 5-year course of MTX therapy. The present study indicated a rare case in which the LPD had spread to multiple bones in a patient with a pathologic fracture. Notably, the LPD was subclassified as diffuse large B-cell lymphoma (DLBCL).

Skeletal metastasis from sarcoma: a report of three cases

In the present report, we describe the very rare occurrence of soft tissue metastases from sarcoma at four sites in three patients, focusing on the clinical course and radiological features. All soft tissue masses occurred as a result of disseminated metastases from malignant sarcomas. The initial symptoms presented as painful masses. Magnetic resonance imaging demonstrated a non-specific appearance for the skeletal metastases derived from the sarcomas, corresponding to the signal of the primary lesion.

Unplanned resection of a primary malignant bone tumor: a report of three cases

In this paper, we present three cases with unplanned resection of a malignant bone tumor. The first case was a 32-year-old male who underwent resection of a tumor located on the right femur. The tumor was resected as exostosis, but the definitive diagnosis was parosteal osteosarcoma. The second case was a 53-year-old female who received two curettages of a tumor in the right femur as osteoblastoma. The definitive pathological diagnosis was osteosarcoma. The third case was a 78-year-old male who received an inappropriate biopsy procedure by a urologist in a previous institution. The pathological diagnosis was chondrosarcoma. All three cases received incorrect procedures for removal of a malignant bone tumor, due to radiological/pathological misdiagnosis and inappropriate surgical procedures for the skin incisions. Incorrect surgical management has the potential to expand tumor cell contamination into normal adjacent tissues, which would require the creation of a major tissue defect for sufficient removal. Amputation was selected in two cases and carbon ion radiotherapy in one case. Initial surgeons should be aware of the possibility of malignancy when treating bone tumors.