Takeshi Morii

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.

Postoperative deep infection in tumor endoprosthesis reconstruction around the knee

BackgroundAlthough deep infection remains one of the most difficult complications to manage in the treatment of musculoskeletal tumor reconstructed with an endoprosthesis, limited information with respect to its incidence and risk factors has been reported.MethodsThis multicenter, retrospective, uncontrolled study reviewed the medical records of 82 patients who underwent reconstruction with an endoprosthesis or temporary spacer for bone-immature patients after resection of malignant bone tumor around the knee. Risk factors for deep infection and the impact of deep infection on prosthesis survival and oncological outcomes were analyzed. Deep infection was defined according to the Centers for Disease Control and Prevention (CDC) guidelines with minor modification.ResultsDeep infection occurred in 14 cases (17%), identified at a mean of 10.9 months (range <1 to 48 months) after initial surgery. Univariate analysis identified surface infection (P < 0.001) and skin necrosis (P < 0.001) as risk factors associated with deep infection. Conversely, tumor origin, chemotherapy, number of postoperative antibiotics, and length of bone resection were not associated with infection. Subclass analysis in femur cases identified a correlation between infection and the extent of partial resection of the quadriceps muscle (P = 0.04). In the multivariate analysis, surface infection represented an independent risk factor for deep infection (P = 0.03). Deep infection was a risk for endoprosthesis survival (P = 0.003) but did not affect the oncological outcome.ConclusionsA strong correlation between the condition of soft tissue and establishment of deep infection is suggested in this study. Although practical options for preventing deep infection seem limited, the present data allow a form of perioperative evaluation for patients with a higher risk of deep infection.

Malignant Pigmented Villonodular Synovitis in the Knee - Report of a Case with Rapid Clinical Progression

Malignant pigmented villonodular synovitis (PVNS) (or malignant giant cell tumor of tendon sheath (GCTTS) is an extremely rare condition defined as a malignant lesion occurring with concomitant or previously documented PVNS at the same site. To date, only less than 20 cases have been reported in English literatures. We report a case of malignant PVNS in the knee in a 56-year-old woman with unpredictable rapid progression. This case raised a caution that when atypical components in specimens of recurrent benign PVNS are detected, even if low-grade or tiny, both pathologists and surgeons should consider the risk of malignant PVNS, which could display aggressive clinical progression.

Clinical significance of magnetic resonance imaging in the preoperative differential diagnosis of calcifying aponeurotic fibroma

BackgroundAlthough the clinical and histological features of calcifying aponeurotic fibroma are well described, the magnetic resonance imaging (MRI) findings have been reported for only five cases. The purpose of this study was to describe a series of MRI findings in this rare entity to assess its utility in preoperative and differential diagnosis.MethodsMRI findings together with the clinical signs and radiographs of six patients with pathologically proven calcifying aponeurotic fibroma were retrospectively reviewed. Distribution, morphology, margins, edematous changes, and relation to the surrounding structures together with signal intensity of each sequence of MRI were evaluated.ResultsMRI demonstrated subcutaneous distribution, ill-defined appearance, and a tendency to infiltrate into or adhere to the surrounding tissues. The masses were of isointensity to low intensity on T1-weighted images. T2-weighted images showed heterogeneous high signal intensity with minor areas of isointensity to low signal intensity. Postcontrast T1-weighted images demonstrated heterogeneous intense enhancement.ConclusionsMRI revealed several features that can contribute to the preoperative differential diagnosis of calcifying aponeurotic fibroma from other fibrous tumors, giant cell tumor of the tendon sheath, or soft tissue sarcoma. As a result, MRI would help orthopedic oncologists plan the surgery for this rare entity.

Treatment outcome of enchondroma by simple curettage without augmentation

BackgroundSimple curettage for enchondroma without augmentation, known to lead to spontaneous bone consolidation at the curettage site, is a potential standard treatment for this condition. However, few detailed data comparing the results of this technique with conventional methods including reconstruction are available, and the relation between the postoperative completion period for bone consolidation and preoperative independent variables is not known.MethodsThe subjects included 38 patients with enchondroma treated with simple curettage without augmentation. A historical group of patients with enchondroma treated with hydroxyapatite reconstruction was enrolled as controls. Treatment outcomes, including perioperative complications (e.g., infection, functional loss, recurrence, postoperative fracture), were surveyed. Differences in the period needed for bone formation among the patient groups defined by various preoperative patient conditions were also analyzed.ResultsThe follow-up period ranged from 12 to 60 months (average 24.3 months). During the follow-up period, no surgery-related complications occurred. Bone formation was confirmed in all cases 3–20 weeks (average 6.5 weeks) postoperatively. Tumor size represented by two-dimensional measurements was significantly correlated with the bone formation period. Polycystic lesions required a prolonged postoperative bone formation period compared with monocystic lesions. The bone formation period did not significantly differ between the simple curettage group and the historical control group.ConclusionsSimple curettage without augmentation proved to be a safe, promising modality for the treatment of small enchondromas in the hand and foot.

Natural evolution of desmoplastic fibroblastoma on magnetic resonance imaging: a case report

IntroductionDesmoplastic fibroblastoma (collagenous fibroma) is a recently described tumor thought to arise predominantly from subcutaneous tissue or skeletal muscle. The natural evolution of this tumor on magnetic resonance imaging has never been described, to the best of our knowledge. We herein report a case of desmoplastic fibroblastoma arising in the thigh and show the longitudinal magnetic resonance imaging findings.Case presentationA 60-year-old Japanese man presented with swelling of the medial side of his right thigh, and he complained of nighttime pain and slight tenderness. Magnetic resonance imaging demonstrated a 4 × 4 cm mass in the right thigh. Open biopsy was performed. The mass was diagnosed histologically as a benign fibrous tumor, and we maintained follow-up without surgical therapy. After one year, magnetic resonance imaging showed an increase in tumor size to 4 × 5 cm, but the histologic findings were the same as those obtained one year earlier. Resection was performed with narrow surgical margins. Pathologic diagnosis was desmoplastic fibroblastoma. Two years after surgery, the patient is free from pain and shows no signs or symptoms of recurrence.ConclusionThe natural evolution of desmoplastic fibroblastoma is characterized by no changes in patterns on magnetic resonance imaging despite increasing size. This finding is clinically helpful for distinguishing desmoplastic fibroblastoma with increasing pain from the desmoid tumor.

Clinical Significance of Additional Wide Resection for Unplanned Resection of High Grade Soft Tissue Sarcoma

Purpose: Unplanned resection of musculoskeletal sarcoma involves tumor excision without any suspicion of malignancy or regard for the necessity of defining adequate margins. For orthopaedic oncologists, many opportunities arise for management of unplanned resections initially performed by non-specialist surgeons. The puropose of this study is to assess the clinical outcomes and the problems of the patients with unplanned resection of high-grade soft tissue sarcoma. Methods: 77 consecutive patients were retrospectively reviewed. Oncological outcomes together with validity and problems of additional treatments were analyzed. Results: Five-year local recurrence-free survival, metastasis-free survival, event-free survival and total survival were 71.55%, 73.2%, 57.5% and 85.9%, respectively. Among adjuvant therapy including additional wide resection, radiotherapy and systemic chemotherapy, only additional wide resection significantly improved oncological outcomes. Conclusion: Additional wide resection appears to be effective in the treatment of high-grade soft tissue sarcomas following primary resection with compromised margins of resection.

Surgical site infection in malignant soft tissue tumors

BackgroundPostoperative wound complications, including surgical site infections, which frequently occur in the course of management of musculoskeletal sarcomas, sometimes necessitate repeat surgeries, including amputation, and may result in a prolonged healing time, prolonged hospital stay, or fatal outcome. A comprehensive understanding of surgical site infections associated with specific diseases is needed to reduce the risk.MethodsThis series comprised 84 patients with malignant soft tissue tumors treated at our institute. The occurrence rate, management modality and clinical course of surgical site infections, impact of surgical site infections on the length of hospitalization, risk factors for the development of surgical site infections, and the impact of surgical site infections on the oncological outcomes were analyzed. Surgical site infection was defined according to Centers for Disease Control and Prevention guidelines.ResultsSurgical site infections occurred in 7 cases (8.3%). Although successful clinical cure was achieved in all cases, surgical site infection was identified as one of the independent risk factors for prolongation of hospitalization. Both univariate and multivariate analyses identified larger intraoperative blood loss and a trunk location as risk factors associated with deep infections. No association was detected between age, tumor grade, chemotherapy, tumor volume, or plastic surgery and the risk of surgical site infections. Although the differences were not statistically significant, patients with surgical site infections showed worse oncological outcomes in terms of local recurrence and total survival.ConclusionThe incidence rate of surgical site infection was larger than that associated with conventional orthopedic surgeries, such as osteosynthesis, spine surgery, or arthroplasty. Surgical site infections remain a critical and frequent complication of surgical treatment of soft-tissue malignancies and often result in prolongation of hospital stay. Although practical options to prevent surgical site infections seem quite limited, the present data provide a rationale for perioperative evaluation in patients at a high risk of surgical site infections.

Venous thromboembolism in the management of patients with musculoskeletal tumor

BackgroundAlthough patients with musculoskeletal tumors are at risk of venous thromboembolism (VTE), few detailed studies on the incidence, clinical course, and risk factors of this condition have been reported.MethodsA total of 299 patients with musculoskeletal tumors during the preceding 3 years were enrolled. D-dimer (DD) levels on admission and on postoperative days 1, 7, and 14 were routinely assessed. For patients who were receiving chemotherapy, an examination was performed every 2-3 days for the survey. Multidetector-row computed tomography (MDCT) was used for the detection of VTE in patients with DD levels > 10 μg/ml. The incidence of clinically detected VTE and the clinical courses of the patients with VTE were reviewed. The risk factors for VTE were analyzed. For statistical analysis, Fisher’s exact test, the Mann-Whitney U-test, and logistic regression were used.ResultsVTE was detected in eight cases (2.7%). Six cases were detected postoperatively, and the remaining two cases were detected during chemotherapy. Pulmonary embolism was evident in four cases. No VTE-related lethal events were detected during the study period. In the univariate analysis, malignancy (P = 0.003), chemotherapy (P = 0.004), plastic surgery (P = 0.006), tumor size (P = 0.008), and elevated DD levels at admission (P = 0.03) were found to be significant risk factors for VTE. Among these factors, the multivariate analysis indicated that tumor size (P = 0.00 006), plastic surgery (P 0. 01), and chemotherapy (P = 0.02) were independent risk factors.ConclusionsThe incidence and risk factors for VTE in the management of musculoskeletal tumor patients by screening DD levels combined with MDCT were analyzed. For patients at risk, prospective surveys for VTE should be considered in the future.

Short-term postoperative mortality events in patients over 80 years of age with hip fracture: analysis at a single institution with limited medical resources

BackgroundLethal events represent the most important complication in the treatment of hip fracture in elderly patients. Despite the increasing chance for treatment of such conditions, few data regarding risk factors associated with lethal events have been determined for ordinary hospitals with limited medical and human resources, particularly in Japan.MethodsThe incidence of postoperative lethal events and related preoperative risk factors in extremely elderly patients (>80 years) with hip fracture were retrospectively analyzed in our hospital for the past 2 years.ResultsLethal events occurred in 11 (10.7%) of 103 patients within 3 months postoperatively. In both univariate and multivariate analyses, an elevated number of co-morbidities and preoperative respiratory dysfunction were identified as significant risk factors. Delay in surgery was not a risk factor for lethal events.ConclusionsA valid reason for delay is the need to stabilize concurrent medical conditions due to multiple co-morbidities in extremely elderly patients with hip fracture. Considering the limited resources and extreme age of the subjects, the mortality rate in the present study was quite acceptable. Patients, families of patients, and physicians should recognize the increased risk of mortality for patients with significant risk factors in the surgical treatment of hip fracture.