Toshihisa Osanai

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.

Osteosarcomas after the age of 50: a clinicopathologic study of 64 cases--an experience in northern Japan.

Background: The clinicopathologic profile and prognostic factors of osteosarcomas after the age of 50 years have been obscure.Methods: Clinicopathologic features were analyzed in 645 patients with osteosarcoma who were registered at the Tohoku Musculoskeletal Tumor Society and National Cancer Center in Tokyo between 1972 and 2002.Results: Sixty-four patients (9.9%; 34 men and 30 women) were more than 50 years old. The most common location was the distal femur (n = 13), followed by the pelvis (n = 10), proximal femur (n = 9), and proximal fibula (n = 6). Seven (11%) patients had lung metastasis at initial presentation. On radiographs, an osteolytic appearance without periosteal reactions was a common and characteristic feature. Forty-eight tumors (75%) were classified as conventional osteosarcomas. Fourteen cases (22%) were secondary; postradiation osteosarcoma was most common in these patients, but there was no Paget’s sarcoma. At the initial presentation, misdiagnoses without biopsy were made in 15 (23%) of the 64 cases. Preoperative chemotherapy was given to 22 patients, but the effect was poor in 18 cases (82%). Fifty-four patients underwent surgery, whereas the other 10 patients were treated without surgery because of systemic or inoperable local conditions. The overall survival rate at 5 years was 55.5%. Multivariate analysis showed initial pulmonary metastasis, axial tumor location, and larger tumors as significant prognostic factors.Conclusions: In northern Japan, most patients with osteosarcoma after the age of 50 had primary osteosarcoma. Careful radiological examination and biopsy are mandatory for correct diagnosis. Current systemic chemotherapy is not effective for this age group. Alternative treatment strategies should be considered.

Hibernomas show intense accumulation of FDG positron emission tomography.

We present 2 cases of hibernoma. Positron emission tomography using the glucose analog [18F]fluoro-2-deoxy-d-glucose (FDG) of 2 patients with hibernoma showed intense accumulation. Standardized uptake values (SUVs) in these patients were 11.93 and 26.74, values much higher than the SUVs reported in published studies of liposarcomas. Standardized uptake values of FDG positron emission tomography may thus be able to differentiate hibernomas from liposarcomas.

Clinical Relevance of Pathological Grades of Malignant Peripheral Nerve Sheath Tumor: A Multi-Institution TMTS Study of 56 Cases in Northern Japan

BackgroundMalignant peripheral nerve sheath tumor (MPNST) is a relatively rare soft tissue tumor, and its clinical relevance of pathological grades remains obscure.MethodsFifty-six cases of MPNST identified from the files of seven oncology centers of the Tohoku Musculoskeletal Tumor Society (TMTS) and National Cancer Center were analyzed for histologic grades, demographics, treatments, and prognostic factors. The average follow-up period was 41 months.ResultsTwenty-two men and 34 women with a mean age of 45 years were involved. Forty-four (78.6%) of 56 tumors were in the lower extremity or trunk. Fifty tumors (89%) were classified as high grade, and the remaining six as low grade. Twenty-one (39.6%) of 53 patients who underwent tumor excision developed local recurrences. An axial site and inadequate surgical margin were defined as risk factors for local recurrence. The overall survival rates of the 56 patients were 55.1% at 3 years and 43.3% at 5 years. Univariate analysis of the 56 patients revealed large-sized tumors, metastasis at presentation, and histologically high grade were significantly associated with poor prognosis. Multivariate analysis revealed a large tumor and metastasis at presentation to be independent prognostic factors.ConclusionsThe current study involving 56 patients with MPNST showed the aggressive clinical behavior of the tumor. Large-sized tumors, metastasis at presentation, and high histological grade were related to poor prognosis on univariate analysis, but independency of histological grade was still obscure. In the treatment for a large and high-grade MPNST, an alternative strategy should be further considered.

Gastrocnemius muscle flap including Achilles tendon after extensive patellectomy for soft tissue sarcoma.

A 72-year-old man developed a soft-tissue sarcoma anterior to his left knee. The tumour was excised widely combined with an extensive patellectomy. A gastrocnemius flap including Achilles tendon was used successfully to cover the soft-tissue defect and to reconstruct the knee extensor mechanism.

Osteosarcoma of the proximal fibula. An analysis of 13 cases in the northern Japan.

Osteosarcoma is the most common form of malignant bone tumor that occurs during childhood and adolescence. The proximal fibula is a relatively rare site for osteosarcoma. We reviewed 305 cases of osteosarcoma registered at the Tohoku Musculoskeletal Tumor Society (TMTS) between 1975 and 1999. Thirteen patients (4.3%) had their osteosarcomas localized in the proximal fibula. Conventional fibroblastic osteosarcoma accounted for 46% of the cases in this series. Limb-sparing surgery was performed in all 13 patients during initial surgery, and the peroneal nerve was preserved in 4 cases. These 4 cases developed local recurrences, but additional wide excision or radiation had a beneficial effect on the recurrences. In our series, the patients showed a 5-year survival rate 76 per cent. The postoperative function of the knee remained good despite various reattachment procedures of lateral co-lateral ligament. As well as resection of the proximal fibula, our results indicate that osteosarcoma of the proximal fibula has a good prognosis for cases who undergo adequate initial surgery.

Localization of blood coagulation factors and fibrinolysis factors within lymphoid germinal centers in human lymph nodes

SummaryThe presence of nineteen blood coagulation factors and fibrinolysis factors was immunohistochemically evaluated in human lymph node germinal centers (GCs). Twelve of these factors were detected within lymphoid GCs. The predominant pattern was dendritic with occasional crescent-shaped, ring-shaped or ‘moth-eaten’ appearance. Immunostains of factor VIII-related antigen, factor I, protein C, tetranectin, antithrombin III, type 2-plasminogen activator inhibitor, and α2-plasmin inhibitor were almost entirely absent from GCs, although they reacted in vascular wall and lumen, respectively. The immunostaining to high molecular weight kininogen, kallikrein, factors XII, X, V, II, XIIIa, XIIIs, plasminogen, tissue-plasminogen activator, and type 1-plasminogen activator inhibitor more frequently revealed a positive dendritic pattern. Immuno-electron microscopy demonstrated factor X and factor XIIIa attached to the cell surfaces of lymphocytes, macrophages, and follicular dendritic cells (FDCs); and in the intercellular space within GCs, especially attached to the labyrinthine-like structure of FDCs. No reaction products were observed in the perinuclear cisternae and rough endoplasmic reticulum in either lymphocytes or FDCs. Our data demonstrate that human lymphoid GCs really contain some of the proteins related to the blood coagulation and fibrinolysis cascades.

Modified digital tourniquet designed to prevent the tourniquet from inadvertently being left in place after the end of surgery.

Digital tourniquets have been used worldwide in finger and toe surgery. Digital tourniquets of various types have been used, and a rolled glove technique provides a simple and quick method. We have modified a rolled glove technique to prevent iatrogenic complications associated with digital tourniquets being inadvertently left in place after surgery.

Histologic Examination of Leeds-Keio Artificial Ligament Implanted on the Surface of a Tumor Endoprosthesis

The Leeds-Keio (L-K) artificial ligament is made of polyester fibers with an open-weave mesh structure. It has been used clinically for knee ligament reconstruction as a scaffold, allowing tissue ingrowth and new ligament formation. We have used the L-K ligament in bone tumor surgery for reattaching remaining muscles to the target zone of a tumor endoprosthesis. We histologically examined the L-K ligament obtained from 2 patients during revision surgery 39 months after the primary surgery. There were dense fibrous tissues between muscles and the L-K ligament. Collagen fibers proliferated in the space between the polyester fibers, and a slight inflammatory reaction was apparent. We concluded that the L-K ligament had a high potential for inducing biological tissue regeneration even on the metal surface.

Ochronotic spondylarthropathy: two case reports of progressive destructive changes in the hip

Abstract We report two cases of ochronotic spondylarthropathy who presented with spinal involvement followed by progressive destructive changes in the hip joint, which led to total hip replacement with a satisfactory outcome. Pathological examination revealed severe deterioration of the affected hip with unique cartilage degeneration associated with active inflammation in the synovium and bone marrow. These features were also evaluated by magnetic resonance imaging in one case which presented with rapidly destructive changes in the hip. Spinal involvement may contribute to progressive destructive hip arthropathy in ochronosis.