Takashi Shimoji

HOXB2 as a Novel Prognostic Indicator for Stage I Lung Adenocarcinomas

Background: Outcomes of patients with lung adenocarcinomas can be predicted to some extent from the pathologic stage (p-stage). Although all attempts are made to fully remove cancer lesions, still a number of p-stage I patients without metastatic disease at the time of surgery develop recurrences and die of cancer. It is thus very important to identify p-stage I patients who are at risk of recurrence. Methods: Previously, using microdissected samples, we identified metastasis-related genes. Using real-time reverse-transcriptase polymerase chain reaction analysis, we investigated the transcriptional levels of the top metastasis-related genes using 96 independent test lung adenocarcinoma samples and investigated their correlations with the prognosis. Results and Conclusions: We document evidence that p-stage I patients with HOXB2 up-regulation have a worse prognosis than those with HOXB2 down-regulation (p = 0.0065), whereas the HOXB2 status has no prognostic significance for p-stage II–IV patients. Comparing tumors and corresponding normal lung tissue, we confirmed HOXB2 up-regulated lesions to have much higher HOXB2 expression than the corresponding normal tissue. Confirmation with a larger number of samples is needed, with further research to clarify the molecular functions of HOXB2.

Incidence of Pneumothorax in Advanced and/or Metastatic Soft Tissue Sarcoma Patients during Pazopanib Treatment

Sird After pazopanib’s approval for the treatment of soft tissue sarcomas, pneumothorax was reported as an unexpected adverse event linked to pazopanib treatment. Pneumothorax was rarely reported in the pre-approval clinical trials of pazopanib [1], so the incidence of pneumothorax during pazopanib treatment has not yet been established. We retrospectively reviewed the cases of 32 soft tissue sarcoma patients treated with pazopanib between November 2012 and December 2013 at our institute. The median follow-up time was 3.1 months (range 0.3e9.6

How Long Should We Follow Patients With Soft Tissue Sarcomas

BackgroundGuidelines suggest that followup for low-grade soft tissue sarcomas should be every 3 to 6 months for 2 to 3 years and then annually, and for high-grade sarcomas every 3 to 6 months for 2 to 5 years, then every 6 months for the next 2 years, and then annually. However, there is only very limited evidence to support these strategies.Questions/purposesIn a population of patients treated surgically for soft tissue sarcomas, we evaluated the (1) timing of diagnosis of local recurrences after sarcoma excision; (2) timing of diagnosis of distant metastases; and (3) the difference in those parameters based on tumor size and grade.MethodsPatients diagnosed with soft tissue sarcomas and who underwent surgical excision between 1978 and 2008 were retrospectively reviewed. Age, histologic diagnosis, Fédération Nationale des Centres de Lutte Contre le Cancer (FNCLCC) grade, tumor location, and size were reviewed at a mean of 6 years (range, 1 month to 30 years). We met with patients every 3 months for 5 years, every 6 months for 10 years, and then annually until 15 years after surgery. Eight hundred sixty-seven patients with a median age at diagnosis of 52 years were eligible for analysis. The incidence of local recurrence and metastases was calculated for every 2-year period and presented per 1000 person-years.ResultsNinety-eight patients (11%) developed local recurrence at a median time of 19 months; 90% of patients who had local recurrences had them within 7.1 years, and 95% occurred by 8.6 years. One hundred ninety-eight patients (23%) developed distant metastases at a median time of 12 months; 90% of patients who developed metastases developed them by 4.2 years and 95% did so by 7.3 years. High-grade tumors had a higher incidence of local recurrence and metastases in first 2 years, whereas low-grade tumors recurred at a constant rate throughout the followup period.ConclusionsFollowup beyond 10 years does not yield a sufficient number of local recurrences or metastases to warrant further monitoring.Level of EvidenceLevel II, prognostic study. See Guidelines for Authors for a complete description of levels of evidence.

A new technique using mesh for extensor reconstruction after proximal tibial resection

BACKGROUND Proximal tibial reconstruction following wide resection in both malignant and benign tumors presents difficulties mainly due to both patellar tendon reconstruction and high risk of infection. The purpose of this study is to determine the efficacy of a new technique using a mesh for extensor reconstruction. METHODS We retrospectively reviewed nine consecutive patients who underwent resection of the proximal tibia with prosthetic reconstruction and reconstruction of the extensor using a mesh between 2009 and 2012. The surgical technique included the attachment of the mesh to the tibial component with a band of meshes looped over the patella and a gastrocnemius flap for coverage. RESULTS One patient had an above-the-knee amputation due to infection. Eight patients were followed up for 33 months (range, 20-50). In the eight patients, extensor lag had a mean of 5° (range, 0 to 20). Active flexion had a mean of 96.25° (range, 80 to 120) and ISOLS scores had a mean of 21/30 (range, 18 to 26). All patients were able to ambulate without crutches at the latest follow-up. CONCLUSION Extensor lag was significantly less compared to previous reports. No complications were observed in eight patients. Utilization of the mesh for extensor reconstruction after the proximal tibial resection is a simple, reliable and successful method.

New endoprosthesis suspension method with polypropylene monofilament knitted mesh after resection of bone tumors in proximal humerus

BACKGROUND Endoprosthetic reconstruction of the proximal humerus is one of the standard procedures after resection of tumors of the proximal humerus and has been considered a reliable method to reconstruct the proximal humerus in recent reports. However, instability of the shoulder joint caused by loss of the rotator cuff and deltoid muscle function is often observed after such an endoprosthetic reconstruction. METHODS We performed the endoprosthesis suspension method with polypropylene monofilament knitted mesh. This suspension method, by which the endoprosthesis is suspended from the bone structure, was used after resection of tumors in 9 patients. We assessed postoperative stability of the shoulder joint by comparing these patients with 12 patients who underwent the conventional surgical technique, by which the mesh-wrapped endoprosthesis is attached only to soft tissue. RESULTS In radiographic and physical evaluation, 4 of the 12 patients in the soft tissue reconstruction group showed shoulder joint instability. No patient in the suspension method group showed subluxation of the humeral prosthesis. The mean shoulder flexion was 35° and 65° and the mean shoulder abduction was 40° and 40° for the soft tissue reconstruction group and the suspension method group, respectively. DISCUSSION Shoulder joint subluxation sometimes occurs because of elongation of the attached soft tissue in the conventional reconstruction with mesh, whereas no shoulder joint subluxation occurs after endoprosthetic reconstruction in the suspension method because the bone structure has no leeway for elongation. Excellent stability of our new method enables exercise of the surgical shoulder at an early stage, leading to improved range of shoulder joint motion.

Cytogenetic study of secondary malignancy in giant cell tumor.

Giant cell tumor (GCT) is classified as a benign bone tumor, but it is locally aggressive, and sometimes metastasizes in a benign state. In addition, malignant transformation occurs once in a while. Most of the secondary malignancies in GCT occur after treatment of benign GCT that has included radiation therapy [1, 2]. As a cytogenetic characteristic of GCT, telomeric associations (tas) were reported [3, 4]. Tas may generate dicentric chromosomes (dic) and chromatoid breakagefusion-bridges, which lead to chromosomal instability and tumorigenesis [5, 6]. Recently, the relationship between cytogenetic abnormalities and clinical behavior in GCT has begun to be elucidated. For example, the DNA ploidy pattern may predict the recurrence potential of GCT, chromosomal abnormalities superimposed on tas are responsible for an aggressive clinical course [7], and centrosome amplification may be useful in predicting the clinical behavior of GCT [8]. Here we report a case of secondary malignancy in GCT. Malignant transformation occurred in a relatively early period, and any radiation therapy was not administered to the primary lesion. Malignant transformation was demonstrated not only by histopathological study but also by cytogenetic analysis. The recurrent tumor, which was a secondary malignancy in GCT, had a near-triploid karyotype with multiple structural abnormalities as observed in pleomorphic sarcoma, while the primary benign GCT had a near-diploid karyotype with tas and dic.

Osteosarcoma arising in fibrous dysplasia, confirmed by mutational analysis of GNAS gene

Malignancy arising in fibrous dysplasia (FD) is rare. Approximately 100 cases have been reported so far, and osteosarcoma is the most common malignancy. We report a case of osteosarcoma in a 33-year-old Japanese man with monostotic FD of the right proximal femur from the age of 16 years. Histologically, relatively well-differentiated osteosarcoma was found in the FD lesion. Immunohistochemically, the FD was negative for p53 or MDM2, and the MIB-1 index was less than 1%, whereas the osteosarcoma was positive for both p53 and MDM2, and the MIB-1 index was up to 15%. The FD and osteosarcoma were negative for CDK4. Fluorescent in situ hybridization assay showed no amplification of the MDM2 gene, indicating that the osteosarcoma was a conventional osteosarcoma, not an intraosseous well-differentiated type. The original cell of malignancy in FD is unclear. Malignancy can be potentially derived from dysplastic cells in the area of the FD or cells in the adjacent normal tissues. GNAS gene mutation has recently been reported for fibrous dysplasia and the mutation is highly specific to fibrous dysplasia among fibro-osseous lesions including osteosarcoma. In this case, point mutations of GNAS were found in the FD and osteosarcoma but not in the adjacent normal tissues, suggesting that osteosarcoma was derived from the spindle cells of FD. This is the first report to clearly show that osteosarcoma is derived from the spindle cells in fibrous dysplasia (FD).

Hepatoid tenosynovial giant cell tumor – A rare morphologic variant case report

We report a morphologically rare type of tenosynovial giant cell tumor (TSGCT), localized type, occurring in a 49-year-old man. Imaging examination revealed multiple nodular lesions around the right knee joint. The largest one extended to both intra- and extra-osseous region of the right distal femur. Histologically, the tumor consisted of epithelioid mononuclear cells and they looked like to have abundant eosinophilic cytoplasm reminiscent of hepatic tissues. In some areas, however, typical histologic features of TSGCT were observed. Electron microscopy revealed that the eosinophilic cytoplasm-like substance was intercellular fibrinous material surrounding the mononuclear tumor cells. Immunohistochemically, mononuclear tumor cells and multinucleate giant cells were positive for CD68 (Kp1) and some of the mononuclear tumor cells were also positive for desmin. Finally, we made the diagnosis of hepatoid TSGCT.

Intraneural metastasis of gastric carcinoma leads to sciatic nerve palsy

BackgroundSoft tissue metastases, in particular intraneural metastasis, from any carcinomas seldom occur. To our knowledge, no case of sciatic nerve palsy due to intraneural metastasis of gastric carcinoma is reported in the literature.Case presentationA case is reported of a 82-year old woman with sciatic nerve palsy with intraneural metastasis of gastric carcinoma. Although she had undergone partial gastrectomy with T2b, N0, M0 two years ago and primary site was cured, she developed sciatic nerve palsy from the carcinoma metastasis directly to the nerve. Operative resection and Histological examination revealed poorly differentiated adenocarcinoma, the same as her primary site adenocarcinoma.ConclusionsSciatica is usually caused by a herniated disc or spinal canal stenosis. Sciatic nerve palsy may be caused by nondiscogenic etiologies that may be either intrapelvic or extrapelvic. It is important to image the entire course of the nerve to distinguish these etiologies quickly. The longer the nerve compression the less likely a palsy will recover. Surgery is a good intervention that simultaneously obtains a tissue diagnosis and decompresses the nerve.