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2.
Int J Surg ; 11(2): 173-7, 2013.
Article in English | MEDLINE | ID: mdl-23274553

ABSTRACT

This study seeks to discuss the efficiency of minimally invasive surgery of posterior long segmental fixation plus direct decompression in patients with spinal metastatic tumors. Twenty-five patients received minimally invasive surgery of long segmental fixation combined with direct decompression from posterior approach. Pain and neurologic improvement in these patients pre- and post operation were evaluated by Denis' Pain Scale and Frankel Score, respectively. Seventeen patients (68.0%) showed significant decreases in Denis' Pain score after surgery (p < 0.0001). Paralysis symptoms were improved in nineteen patients (76.0%). The Frankel Score exhibited significant difference between pre-operation and post-operation (p < 0.0001). Operation time and blood loss in this cohort were 324 ± 90 min and 1047 ± 730 ml, respectively. No fatal complications were observed as a result of surgery. In conclusion, minimally invasive surgery of posterior long segmental fixation combined with direct decompression is a safe and efficient strategy to release pain and improve neurological function in patients with spinal metastatic tumors.


Subject(s)
Internal Fixators , Minimally Invasive Surgical Procedures/instrumentation , Minimally Invasive Surgical Procedures/methods , Orthopedic Procedures/instrumentation , Orthopedic Procedures/methods , Spinal Neoplasms/secondary , Spinal Neoplasms/surgery , Adult , Aged , Chi-Square Distribution , Female , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Pain/diagnosis , Pain/etiology , Pain Measurement , Prognosis , Retrospective Studies , Spinal Neoplasms/physiopathology , Treatment Outcome
4.
Mol Cancer Ther ; 9(3): 535-44, 2010 Mar.
Article in English | MEDLINE | ID: mdl-20159990

ABSTRACT

Pulmonary metastasis is the most significant prognostic determinant for osteosarcoma, but methods for its prediction and treatment have not been established. Using oligonucleotide microarrays, we compared the global gene expression of biopsy samples between seven osteosarcoma patients who developed pulmonary metastasis within 4 years after neoadjuvant chemotherapy and curative resection, and 12 patients who did not relapse. We identified argininosuccinate synthetase (ASS) as a gene differentially expressed with the highest statistical significance (Welch's t test, P = 2.2 x 10(-5)). Immunohistochemical analysis of an independent cohort of 62 osteosarcoma cases confirmed that reduced expression of ASS protein was significantly correlated with the development of pulmonary metastasis after surgery (log-rank test, P < 0.05). Cox regression analysis revealed that ASS was the sole significant predictive factor (P = 0.039; hazard ratio, 0.319; 95% confidence interval, 0.108-0.945). ASS is one of the enzymes required for the production of a nonessential amino acid, arginine. We showed that osteosarcoma cells lacking ASS expression were auxotrophic for arginine and underwent G(0)-G(1) arrest in arginine-free medium, suggesting that an arginine deprivation therapy could be effective in patients with osteosarcoma. Recently, phase I and II clinical trials in patients with melanoma and hepatocellular carcinoma have shown the safety and efficacy of plasma arginine depletion by stabilized arginine deiminase. Our data indicate that in patients with osteosarcoma, reduced expression of ASS is not only a novel predictive biomarker for the development of metastasis, but also a potential target for pharmacologic intervention.


Subject(s)
Argininosuccinate Synthase/genetics , Bone Neoplasms/diagnosis , Lung Neoplasms/diagnosis , Lung Neoplasms/secondary , Osteosarcoma/diagnosis , Adolescent , Adult , Argininosuccinate Synthase/metabolism , Argininosuccinate Synthase/physiology , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , Biomarkers, Tumor/physiology , Bone Neoplasms/genetics , Bone Neoplasms/mortality , Bone Neoplasms/pathology , Child , Down-Regulation/physiology , Female , Gene Expression Profiling , Gene Expression Regulation, Enzymologic/physiology , Gene Expression Regulation, Neoplastic/physiology , Humans , Lung Neoplasms/genetics , Lung Neoplasms/mortality , Male , Oligonucleotide Array Sequence Analysis , Osteosarcoma/genetics , Osteosarcoma/mortality , Osteosarcoma/pathology , Prognosis , Tumor Cells, Cultured , Young Adult
5.
Cancer Sci ; 100(12): 2268-74, 2009 Dec.
Article in English | MEDLINE | ID: mdl-19725836

ABSTRACT

Osteosarcoma (OS) is the most frequent primary malignant bone tumor of children and young adults. Although the introduction of combined neoadjuvant chemotherapy has markedly improved survival, the outcome of OS patients with distant metastasis and/or poor response to chemotherapy is still unsatisfactory. Therefore there is a need to develop new therapeutic agents that suppress OS cell proliferation with higher efficacy. The protein kinases are a family of genes that play critical roles in various signaling pathways. Some cancer cells show addiction to constitutive activation of certain signaling pathways for proliferation and survival. To identify new drug targets for OS, we screened a panel of small interfering RNAs (siRNAs) that target 691 genes encoding human protein kinases and related proteins. We found that different constructs of siRNA specifically targeting polo-like 1 kinase (PLK1) significantly caused mitotic cell cycle arrest and subsequent apoptotic cell death in a variety of OS cell lines. siRNA targeting PLK1 also suppressed the growth of OS xenografts established in immunodeficient mice. Recently, phase I clinical trials of PLK1 chemical inhibitors have been reported. Our results indicate that PLK1 is a promising molecular target for pharmacologic intervention in OS.


Subject(s)
Bone Neoplasms/therapy , Cell Cycle Proteins/antagonists & inhibitors , Osteosarcoma/therapy , Protein Serine-Threonine Kinases/antagonists & inhibitors , Proto-Oncogene Proteins/antagonists & inhibitors , RNA, Small Interfering/therapeutic use , Animals , Bone Neoplasms/genetics , Cell Cycle Proteins/genetics , Cell Line, Tumor , Humans , Male , Mice , Mice, Inbred BALB C , Osteosarcoma/genetics , Protein Serine-Threonine Kinases/genetics , Proto-Oncogene Proteins/genetics , Polo-Like Kinase 1
6.
J Clin Oncol ; 26(25): 4100-8, 2008 Sep 01.
Article in English | MEDLINE | ID: mdl-18757323

ABSTRACT

PURPOSE: The majority of gastrointestinal stromal tumors (GIST) can be cured by surgery alone, but relapse occurs in 20% to 40% of cases. GISTs are considered to invariably arise through gain of function KIT or PDGFA mutation of the interstitial cells of Cajal (ICC). However, the genetic basis of the malignant progression of GISTs are poorly understood. PATIENTS AND METHODS: The expression levels of 54,613 probe sets in 32 surgical samples of untreated GISTs of the stomach and small intestine were analyzed with oligonucleotide microarrays. The representative GeneChip data were validated by real-time reverse transcriptase polymerase chain reaction and immunohistochemistry. RESULTS: Unbiased hierarchical clustering consistently separated the 32 cases of GIST into two major classes according to tumor site. The two major classes were further separated into novel subclasses, which were significantly correlated with various pathological prognostic parameters, the frequency of metastasis (P < .05), and clinical outcome. Immunohistochemical analysis of 152 independent patients with gastric GISTs revealed that the expression of dipeptidyl peptidase IV (T-cell activation antigen CD26) protein was significantly associated with poorer overall and disease-free survival (P < .00001). CONCLUSION: CD26 appears to be a reliable biomarker of malignant GISTs of the stomach. The postoperative recurrence rate of CD26-negative cases was as low as 2.0% (two of 102). Therefore, postoperative follow-up of such patients might be made less intensive. CD26 may play an important role in the malignant progression of gastric GISTs and serve as a therapeutic target.


Subject(s)
Biomarkers, Tumor/biosynthesis , Dipeptidyl Peptidase 4/biosynthesis , Gastrointestinal Stromal Tumors/diagnosis , Gastrointestinal Stromal Tumors/metabolism , Gene Expression Profiling/methods , Gene Expression Regulation, Neoplastic , Cluster Analysis , Coiled Bodies/metabolism , Gastrointestinal Stromal Tumors/genetics , Humans , Immunohistochemistry/methods , Oligonucleotide Array Sequence Analysis , Platelet-Derived Growth Factor/genetics , Prognosis , Proto-Oncogene Proteins c-kit/genetics , Recurrence , Reverse Transcriptase Polymerase Chain Reaction
7.
Clin Cancer Res ; 14(17): 5348-56, 2008 Sep 01.
Article in English | MEDLINE | ID: mdl-18765526

ABSTRACT

PURPOSE: An invasive growth pattern is one of the hallmarks of pancreatic ductal carcinoma. Actinin-4 is an actin-binding protein associated with enhanced cell motility, invasive growth, and lymph node metastasis. Actinin-4 might play an important role in the development and progression of pancreatic cancer. EXPERIMENTAL DESIGN: The expression of actinin-4 was examined immunohistochemically in 173 cases of invasive pancreatic ductal carcinoma. The copy number of the actinin-4 (ACTN4) gene was calculated by fluorescence in situ hybridization. The expression of actinin-4 was stably knocked down by short hairpin RNA, and tumorigenicity was evaluated by orthotopic implantation into mice with severe combined immunodeficiency. RESULTS: The expression level of actinin-4 was increased in 109 (63.0%) of 173 cases of pancreatic cancer. Kaplan-Meier survival curves revealed that patients with increased expression of actinin-4 had a significantly poorer outcome (P=0.00001, log-rank test). Multivariate analysis by the Cox proportional hazard model showed that high expression of actinin-4 was the most significant independent negative predictor of survival (hazard ratio, 2.33; P=0.000009). Amplification (defined as more than four copies per interphase nucleus) of the ACTN4 gene was detected in 11 (37.9%) of 29 cases showing increased expression of actinin-4. Knockdown of actinin-4 expression inhibited the destructive growth of cancer cells in the pancreatic parenchyma. CONCLUSION: Recurrent amplification of chromosome 19q13.1-2 has been reported in pancreatic cancer, but the exact target gene has not been identified. Actinin-4 contributes to the invasive growth of pancreatic ductal carcinoma, and ACTN4 is one of the candidate oncogenes in this chromosome locus.


Subject(s)
Actinin/genetics , Carcinoma, Pancreatic Ductal/genetics , Gene Amplification , Pancreatic Neoplasms/genetics , Actinin/antagonists & inhibitors , Aged , Animals , Cell Line, Tumor , Female , Gene Expression , Humans , Male , Mice , Mice, SCID , Neoplasm Invasiveness , Neoplasm Transplantation , Transfection
8.
J Cancer Res Clin Oncol ; 134(3): 389-95, 2008 Mar.
Article in English | MEDLINE | ID: mdl-17687565

ABSTRACT

PURPOSE: There is some unknown reason Ewing family of tumors (EFTs) is much less common on Asia and Africa than in the Western Caucasian population. This study analyzed the prediction of response and prognostic factors for Ewing family of tumors (EFTs) in an Asian population with a low incidence. METHODS: We retrospectively reviewed 94 patients with EFTs between 1978 and 2006. Fifteen patients received local therapy only. Statistical analyses were performed for 79 patients, including those who received systemic chemotherapy, to identify factors related to chemotherapy responsiveness, event-free survival, and overall survival. RESULTS: Of the 79 patients whose records were analyzed, the 5-year event-free rate and overall survival (OS) rate were 41 and 54%, respectively. The response rate to first-line chemotherapy was 61% in 70 patients with assessable lesions. A significant predictor of response was existence of a non-pelvic primary tumor (P = 0.04). Significant prognostic factors for OS were age, performance status, and metastases at the time of diagnosis (P < 0.01, respectively). Fifty-four patients had disease progression or recurrence after first-line treatment. The time to progression was 3.4 months after salvage treatment. Progression during first-line treatment was significantly associated with time to progression after salvage treatment (P = 0.01). All patients treated without chemotherapy in first-line treatment were recurred with poor prognosis. CONCLUSION: A non-pelvic primary tumor was a favorable predictor of responsiveness to chemotherapy. Chemo-resistant patients might less benefit from second line chemotherapy. Chemotherapy in first-line treatment should not be omitted, even if primary tumor was extirpated completely.


Subject(s)
Bone Neoplasms/diagnosis , Sarcoma, Ewing/diagnosis , Asia , Bone Neoplasms/drug therapy , Bone Neoplasms/epidemiology , Humans , Incidence , Population Groups , Prognosis , Retrospective Studies , Salvage Therapy , Sarcoma, Ewing/drug therapy , Sarcoma, Ewing/epidemiology , Survival Analysis , Treatment Outcome
9.
Radiology ; 245(3): 839-47, 2007 Dec.
Article in English | MEDLINE | ID: mdl-18024454

ABSTRACT

PURPOSE: To retrospectively compare the diagnostic accuracy of positron emission tomography (PET)/computed tomography (CT), PET, conventional imaging, and combined PET/CT and conventional imaging for tumor staging of bone and soft-tissue sarcomas, by using histologic or follow-up imaging findings as the reference standard. MATERIALS AND METHODS: Institutional review board approval was received for this HIPAA-compliant study; informed consent was obtained. Integrated PET/CT was performed in 117 patients (69 male patients, 48 female patients; mean age, 42 years +/- 21 [standard deviation]; range, 9-86 years). Conventional imaging consisted of magnetic resonance imaging of the primary site, chest radiography, whole-body contrast material-enhanced CT, and bone scintigraphy. A total of four reviewers assessed all images. Overall and T staging were evaluated in 69 (59%) patients who underwent surgical removal of the primary tumors and had pathologically proved results. N and M staging were evaluated in all patients, and their reference methods were based on histologic findings (n = 101) and follow-up CT findings (n = 16). RESULTS: Interpretations based on combined PET/CT and conventional imaging findings correctly staged tumors in 60 (87%) of 69 patients, overstaged tumors in eight (12%) patients, and understaged tumors in one (1%) patient. Overall staging accuracy of combined PET/CT and conventional imaging was significantly higher than that at PET (P < .0001). Combined PET/CT and conventional imaging resulted in correct N staging in 114 (97%) of 117 patients and M staging in 109 (93%) of 117 patients. Combined PET/CT and conventional imaging helped reduce overstaging in three (4%) patients and helped change tumor diagnosis from unresectable to resectable in two (2%) patients compared with PET/CT. CONCLUSION: The combination of PET/CT and conventional imaging is accurate in preoperative staging of bone and soft-tissue sarcoma.


Subject(s)
Bone Neoplasms/diagnosis , Fluorodeoxyglucose F18 , Positron-Emission Tomography , Radiopharmaceuticals , Sarcoma/diagnosis , Sarcoma/pathology , Soft Tissue Neoplasms/diagnosis , Tomography, X-Ray Computed , Adolescent , Adult , Aged , Aged, 80 and over , Child , Female , Humans , Male , Middle Aged , Neoplasm Staging , Preoperative Care , Retrospective Studies
10.
J Clin Pathol ; 60(4): 410-4, 2007 Apr.
Article in English | MEDLINE | ID: mdl-16822878

ABSTRACT

AIMS: To study the immunoexpression of cyclo-oxygenase (COX) 2 in osteoblastomas (OBs) and osteosarcomas (OSs), and to assess the utility of immunohistochemical analysis for COX 2 in the differential diagnosis of the two tumour forms. METHODS: The immunohistochemical features of COX 2 were studied in 11 OBs and 30 OSs, including 26 high-grade OSs (16 osteoblastic, 7 chondroblastic, and 3 fibroblastic) and 4 low-grade OSs. RESULTS: Tumour cells from all 11 OBs unequivocally showed diffuse, intense and cytoplasmic immunoreactivity for COX 2. Strong cytoplasmic expression of COX 2 was observed in 5 of 26 (19%) high-grade OSs, all chondroblastic. In one osteoblastic-type OS, COX 2 was expressed in the chondroblastic component, but this tumour was considered to be COX 2 negative. No COX 2 expression was noted in atypical osteoblastic cells. Staining in the four low-grade OSs was negative. CONCLUSION: The results of immunohistochemical analysis of COX 2 suggest that in addition to the routine histopathological evaluation, COX 2 is a valuable diagnostic marker in the distinction between OB and OS.


Subject(s)
Biomarkers, Tumor/metabolism , Bone Neoplasms/diagnosis , Clinical Enzyme Tests/methods , Cyclooxygenase 2/metabolism , Osteoblastoma/diagnosis , Osteosarcoma/diagnosis , Adolescent , Adult , Bone Neoplasms/pathology , Child , Diagnosis, Differential , Female , Humans , Immunoenzyme Techniques , Male , Middle Aged , Osteoblastoma/pathology , Osteosarcoma/pathology
11.
Skeletal Radiol ; 36(6): 523-9, 2007 Jun.
Article in English | MEDLINE | ID: mdl-17139504

ABSTRACT

The rare coexistence of intramuscular myxoma (IM) and fibrous dysplasia (FD) is known as Mazabraud's syndrome. IM tends to occur multifocally and is associated most frequently with polyostotic FD in Mazabraud's syndrome. We present an extremely rare combination of a solitary IM and monostotic FD as a variant of Mazabraud's syndrome, and discuss the importance of recognizing this rare coexistence for appropriate management of the patient.


Subject(s)
Fibrous Dysplasia, Monostotic/diagnosis , Muscle Neoplasms/diagnosis , Myxoma/diagnosis , Biopsy , Contrast Media , Diagnosis, Differential , Female , Fibrous Dysplasia, Monostotic/surgery , Gadolinium DTPA , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Muscle Neoplasms/surgery , Myxoma/surgery , Radiopharmaceuticals , Syndrome , Technetium Tc 99m Medronate , Thigh , Tomography, Emission-Computed , Tomography, X-Ray Computed
12.
Jpn J Clin Oncol ; 37(12): 955-60, 2007 Dec.
Article in English | MEDLINE | ID: mdl-18211986

ABSTRACT

BACKGROUND: The glucose transporter protein 1 (Glut-1) overexpression is associated with poor overall survival (OS) in various malignant tumors. The aim of this study was to investigate prognostic significance of Glut-1 overexpression in patients with bone and soft-tissue sarcomas. METHODS: A total of 67 patients (mean age, 43 years; range, 8-79 years) with bone and soft tissue sarcomas were analyzed. Pathologic confirmation was observed from surgical specimens in all patients. Pathologic variables including tumor differentiation, necrosis, mitotic index, MIB-1 (Ki-67) grade and Glut-1 expression were assessed. Clinical characteristics and pathologic variables were determined by Kaplan-Meyer curve of OS after treatment. RESULTS: Glut-1 overexpression was found in 56 patients (83%). The patients with Glut-1 overexpression showed significantly poor OS compared with those without Glut-1 overexpression (P = 0.029). The presence of metastasis, treatment without surgical resection, tumor differentiation, necrosis, mitotic index and MIB-1 grade were also significantly negative prognostic factors. The presence of metastasis was independently associated with poor OS (P = 0.031). CONCLUSIONS: Assessment of Glut-1 expression prior to treatment has a predictive potential effect in patients with bone and soft-tissue sarcomas.


Subject(s)
Biomarkers, Tumor/analysis , Bone Neoplasms/chemistry , Glucose Transporter Type 1/analysis , Sarcoma/chemistry , Adolescent , Adult , Aged , Analysis of Variance , Bone Neoplasms/therapy , Chemotherapy, Adjuvant , Child , Female , Gene Expression Regulation, Neoplastic , Humans , Immunohistochemistry , Kaplan-Meier Estimate , Male , Middle Aged , Predictive Value of Tests , Prognosis , Prospective Studies , Radiotherapy, Adjuvant , Risk Factors , Sarcoma/therapy , Treatment Outcome , Up-Regulation
13.
Cancer Sci ; 97(10): 1125-8, 2006 Oct.
Article in English | MEDLINE | ID: mdl-16925579

ABSTRACT

The present study was conducted to compare the diagnostic accuracy between carbon-11 choline (11C-choline) positron emission tomography (PET)/computed tomography (CT) and conventional imaging for the staging of bone and soft tissue sarcomas. Sixteen patients who underwent 11C-choline PET/CT prior to treatment were evaluated retrospectively for staging accuracy. Conventional imaging methods consisted of 99,mTc-hydroxymethylene diphosphonate bone scintigraphy, chest CT and magnetic resonance imaging of the primary site. The images were reviewed and a consensus was reached by two board-certified radiologists who were unaware of any clinical or radiological information using hard-copy films and multimodality computer platform. Tumor stage was confirmed by histological examination and/or by an obvious progression in number and/or size of the lesions on follow-up examinations. Reviewers examining both 11C-choline PET/CT and conventional imaging classified T stage in all patients. Interpretation based on 11C-choline PET/CT, the Node (N) stage was correctly diagnosed in all patients, whereas the accuracy of conventional imaging in N stage was 63%. Tumor Node Metastasis (TNM) stage was assessed correctly with 11C-choline PET/CT in 15 of 16 patients (94%) and with conventional imaging in eight of 16 patients (50%). The overall TNM staging and N staging accuracy of 11C-choline PET/CT were significantly higher than that of conventional imaging (P < 0.05). 11C-choline PET/CT is more accurate than conventional imaging regarding clinical staging of patients with bone and soft tissue sarcomas. A whole body 11C-choline PET/CT might be acceptable for imaging studies of tumor staging prior to treatment.


Subject(s)
Bone Neoplasms/diagnosis , Choline , Sarcoma/diagnosis , Adolescent , Adult , Aged , Bone Neoplasms/diagnostic imaging , Carbon Radioisotopes , Female , Humans , Male , Middle Aged , Positron-Emission Tomography , Sarcoma/diagnostic imaging , Tomography, X-Ray Computed
14.
Appl Immunohistochem Mol Morphol ; 14(1): 46-51, 2006 Mar.
Article in English | MEDLINE | ID: mdl-16540730

ABSTRACT

The authors studied the concordance among seven pathologists for the histologic diagnosis, interpretation of KIT immunostaining, and determining MIB-1 labeling indices (LI) in 80 adult patients with primary spindle cell tumors, mainly of the gastrointestinal tract, mesentery, retroperitoneum, and pelvis, based on the review of tissue sections using an immunohistochemical panel of antibodies for KIT/CD117, CD34, desmin, smooth muscle actin (SMA), and S-100 protein. Tumors included 30 gastrointestinal stromal tumors (GISTs), 10 leiomyomas, 10 leiomyosarcomas, 10 schwannomas, 10 solitary fibrous tumors, and 10 desmoid-type fibromatoses. The overall concordance with the original diagnosis of each histologic type was 97.9%, the kappa value ranging from 0.95 to 1.00 (mean 0.97), indicating a perfect agreement. The overall interlaboratory concordance with the original interpretation of KIT immunostaining was 91.3%, the kappa value ranging from 0.77 to 0.90 (mean 0.86). The overall interlaboratory concordance with the original interpretation of KIT immunostaining was 91.9%, the kappa value ranging from 0.72 to 0.93 (mean 0.85). The overall concordance for determining MIB-1 LI was 90% with the original evaluation, and the overall kappa value ranged from 0.62 to 0.86 (mean 0.77). These results indicate that it is possible to reliably diagnose GIST and other spindle cell tumors of the gastrointestinal tract with the use of an immunohistochemical panel of antibodies for KIT, CD34, desmin, SMA, and S-100 protein. Although there is clearly unavoidable inter-observer and interlaboratory variability in the interpretation of KIT immunostained sections and interobserver variability in the determination of MIB-1 LI, the concordance between observes is very acceptable, and in most instances such variability can be eliminated by careful reviewing of the hematoxylin and eosin and immunostained sections.


Subject(s)
Gastrointestinal Neoplasms/diagnosis , Gastrointestinal Stromal Tumors/diagnosis , Proto-Oncogene Proteins c-kit/biosynthesis , Sarcoma/diagnosis , Adult , Antigens, Neoplasm/biosynthesis , Biomarkers, Tumor/biosynthesis , Diagnosis, Differential , Diagnostic Errors/prevention & control , Gastrointestinal Neoplasms/metabolism , Gastrointestinal Neoplasms/pathology , Gastrointestinal Stromal Tumors/metabolism , Gastrointestinal Stromal Tumors/pathology , Humans , Immunohistochemistry , Ki-67 Antigen/biosynthesis , Observer Variation , Sarcoma/metabolism , Sarcoma/pathology
15.
Eur J Nucl Med Mol Imaging ; 33(6): 683-91, 2006 Jun.
Article in English | MEDLINE | ID: mdl-16506050

ABSTRACT

PURPOSE: This study was conducted to investigate whether( 18)F-fluorodeoxyglucose (FDG) uptake, quantified by positron emission tomography (PET), correlates with histological variables including tumour grade, cell proliferation, cell cycle control integrity and glucose metabolism in patients with bone and soft tissue sarcomas. METHODS: Eighty-two patients clinically suspected of having a bone or soft tissue sarcoma underwent FDG PET within 1 week prior to operation and 63 patients (mean age 48 years, range 18-74 years) were enrolled in the complete analysis. We excluded 17 patients with pathologically confirmed benign tumours and two patients with uncontrolled diabetes or concomitant malignancy from data analysis. Maximum and average standardised uptake values (SUVs) of the primary lesion were compared with histological variables including tumour differentiation, the presence of necrosis, MIB-1 score, mitotic score, p53 overexpression, MIB-1 grade, mitotic grade and GLUT-1 expression. RESULTS: Significant correlations were found between maximal and mean SUVs and MIB-1 grade, mitotic grade, MIB-1 score, tumour differentiation and mitotic score. The mean and maximal SUVs were significantly higher in tumours with p53 overexpression than in those without p53 overexpression (p<0.0001). GLUT-1-positive tumours had significantly higher mean (6.5+/-4.2 vs 1.1+/-0.2, p=0.006) and maximal SUVs (8.8+/-5.4 vs 1.7+/-0.5, p=0.005) than the GLUT-1-negative tumours. GLUT-1 intensity correlated positively with both mean (r=0.500, p<0.0001) and maximal SUVs (r=0.509, p<0.0001). Mu ltiple linear regression analysis showed a significant correlation between maximal SUV and MIB-1 grade (p<0.0001). CONCLUSION: The enhanced glucose metabolism, as determined by SUV, is a strong index of tumour grade in bone and soft tissue sarcomas.


Subject(s)
Bone Neoplasms/diagnostic imaging , Bone Neoplasms/metabolism , Fluorodeoxyglucose F18/pharmacokinetics , Glucose Transporter Type 1/metabolism , Glucose/metabolism , Sarcoma/diagnostic imaging , Sarcoma/metabolism , Adolescent , Adult , Aged , Biomarkers/metabolism , Female , Humans , Male , Middle Aged , Positron-Emission Tomography/methods , Prospective Studies , Radiopharmaceuticals/pharmacokinetics , Statistics as Topic
16.
Hum Pathol ; 37(4): 471-6, 2006 Apr.
Article in English | MEDLINE | ID: mdl-16564923

ABSTRACT

Recent studies have shown increased levels of cyclooxygenase (COX)-2 in various human malignancies, including some bone and soft tissue tumors, but little is known about the presence of COX-2 in chondrosarcomas. We performed immunohistochemical staining for COX-2 in 74 chondrosarcomas and compared the staining results with the characteristics and outcome of the patients. Thirty-seven men and 37 women between the ages of 14 and 81 years (median, 50 years) participated in the study. The tumors were located in the axial skeleton in 47 cases and in the long bones in 27 cases. The largest diameters of the tumors ranged from 2.7 to 32 cm (median, 8.0 cm). The immunohistochemistry findings revealed the overexpression of COX-2 in 16 (22%) of the 74 patients. Thirteen (41%) of 32 grade 2 and 2 (67%) of 3 grade 3 chondrosarcomas showed overexpression for COX-2, whereas only 1 (3%) of 39 grade 1 chondrosarcomas showed overexpression. Overexpression of COX-2 was significantly associated with histologic grade (P < .001) and a decreased disease-specific survival (P < .001). These findings suggest that COX-2 overexpression in chondrosarcoma is a negative prognostic factor that may be strongly associated with histologic grade.


Subject(s)
Bone Neoplasms/enzymology , Chondrosarcoma/enzymology , Prostaglandin-Endoperoxide Synthases/metabolism , Adolescent , Adult , Aged , Aged, 80 and over , Bone Neoplasms/pathology , Bone Neoplasms/surgery , Chondrosarcoma/pathology , Chondrosarcoma/surgery , Disease-Free Survival , Female , Humans , Male , Middle Aged , Proportional Hazards Models
17.
Jpn J Clin Oncol ; 35(12): 753-6, 2005 Dec.
Article in English | MEDLINE | ID: mdl-16332719

ABSTRACT

We report a rare case in which two tumor entities, a gastrointestinal stromal tumor (GIST) and Ewing sarcoma/primitive neuroectodermal tumor (ES/PNET), with distinct cytogenetic features occurred in a single patient. The patient was a 72-year-old woman. The first tumor was a submucosal gastric tumor and was diagnosed as a low-risk group GIST based on morphological characteristics and the results of an immunohistochemical analysis for c-kit and CD34. Further cytogenetic analysis revealed that this tumor had a point mutation (D842V substitution) in exon 18 of the platelet-derived growth factor receptor alpha gene. The second tumor was found more than 4 years after the appearance of the first tumor. ES/PNET was highly suspected both morphologically and immunohistochemically, and the diagnosis was confirmed by the detection of an EWS rearrangement using a fluorescence in situ hybridization technique. Although the cytogenetic correlations of these two tumors are unclear, accurate histologic recognition is of clinical importance because the treatments for these two tumors differ.


Subject(s)
Gastrointestinal Stromal Tumors/diagnosis , Neuroectodermal Tumors, Primitive/diagnosis , Retroperitoneal Neoplasms/diagnosis , Sarcoma, Ewing/diagnosis , Stomach Neoplasms/diagnosis , Aged , Antigens, CD34/analysis , Cytogenetic Analysis , Female , Gastrointestinal Stromal Tumors/genetics , Gastrointestinal Stromal Tumors/pathology , Humans , In Situ Hybridization, Fluorescence , Neoplasms, Multiple Primary , Neuroectodermal Tumors, Primitive/genetics , Neuroectodermal Tumors, Primitive/pathology , Point Mutation , Polymerase Chain Reaction , Proto-Oncogene Proteins c-kit/genetics , RNA-Binding Protein EWS/genetics , Receptor, Platelet-Derived Growth Factor alpha/genetics , Retroperitoneal Neoplasms/genetics , Retroperitoneal Neoplasms/pathology , Sarcoma, Ewing/genetics , Sarcoma, Ewing/pathology , Stomach Neoplasms/genetics , Stomach Neoplasms/pathology
18.
J Surg Oncol ; 92(1): 52-8, 2005 Oct 01.
Article in English | MEDLINE | ID: mdl-16180233

ABSTRACT

BACKGROUND AND OBJECTIVES: No organized data regarding the blood losses associated with musculoskeletal tumor surgery has been existed. The present study aimed to examine the extent of blood loss and the transfusion requirement associated with various kinds of musculoskeletal tumor surgeries in a large, well-defined sample. METHODS: The records of 1,047 consecutive operations for musculoskeletal tumors were reviewed. RESULTS: The total blood loss ranged from 0 to 26,050 ml (median: 95 ml). The operative time ranged from 5 to 1,140 min (median: 105 min). There was a significant correlation between the total blood loss and the operative time. The median blood loss was 10 ml in biopsies, 100 ml in curettages, 190 ml in amputations or disarticulations, 30 ml in marginal resections (bone tumors, 50 ml; soft tissue tumors, 25 ml), and 380 ml in wide resections (bone tumors, 2,155 ml; soft tissue tumors, 180 ml). Wide resections for malignant tumors were associated with significantly more blood loss than marginal resections for benign ones. Resections of bone tumors were accompanied by significantly more blood loss than those of soft tissue tumors. Overall, blood transfusions were required after 210 (20.1%) operations. CONCLUSIONS: Our results provide the first exhaustive data about blood loss and the subsequent need for transfusion associated with various kinds of musculoskeletal tumor surgeries that may be helpful for establishing a guideline for perioperative patient management.


Subject(s)
Blood Loss, Surgical , Blood Transfusion , Bone Neoplasms/surgery , Muscle Neoplasms/surgery , Adolescent , Adult , Aged , Child , Child, Preschool , Female , Humans , Male , Middle Aged , Retrospective Studies
19.
Jpn J Clin Oncol ; 35(8): 444-52, 2005 Aug.
Article in English | MEDLINE | ID: mdl-16024533

ABSTRACT

OBJECTIVE: Some studies to date have suggested the development of multiple primary malignancies in patients with soft tissue sarcoma. The current study was performed to quantify the risk of development of multiple primary malignancies in adult patients with soft tissue sarcoma. METHODS: A total of 406 consecutive patients who were diagnosed with soft tissue sarcoma were identified in the study analysis. The cumulative incidence of multiple malignancies was calculated by comparing Kaplan-Meier curves and log-rank tests from each histological type. A Cox proportional hazards model was used to estimate the influence on the hazard ratio (HR) of each variable. RESULTS: A total of 35 patients with soft tissue sarcoma (9%), having preceding (n = 15) and subsequent (n = 20) malignancies other than soft tissue sarcoma were documented. The 5- and 10-year estimated cumulative incidence of multiple primary malignancies were 7.6 and 12.3%, respectively. The hazard risk of multiple primary malignancies adjusted for potential confounding variables was significantly associated with age at diagnosis (HR = 1.51, P = 0.0019). The risk of multiple primary malignancies was also increased in patients with myxofibrosarcoma adjusted by the potential confounding variables (HR = 2.34, P = 0.048). The 5- and 10-year estimated cumulative incidence of multiple primary malignancies in patients with myxofibrosarcoma were both 16.9%. CONCLUSION: The results of our study confirm that the risk of multiple malignancies appears to be impacted by age at the time of diagnosis of the first tumor and by the histological type of myxofibrosarcoma.


Subject(s)
Neoplasms, Second Primary/epidemiology , Sarcoma , Soft Tissue Neoplasms , Adult , Aged , Bone Neoplasms/epidemiology , Breast Neoplasms/epidemiology , Cohort Studies , Confounding Factors, Epidemiologic , Female , Fibrosarcoma/therapy , Humans , Incidence , Lung Neoplasms/epidemiology , Male , Middle Aged , Multivariate Analysis , Neoplasms, Second Primary/etiology , Osteosarcoma/epidemiology , Prognosis , Proportional Hazards Models , Prostatic Neoplasms/epidemiology , ROC Curve , Risk , Sarcoma/therapy , Soft Tissue Neoplasms/therapy
20.
Virchows Arch ; 447(1): 99-102, 2005 Jul.
Article in English | MEDLINE | ID: mdl-15926071

ABSTRACT

Bizarre parosteal osteochondromatous proliferation (BPOP) is a benign lesion that tends to recur repeatedly. Histologically, BPOP contains three components (cartilage, bone, and spindle cells) in differing amounts. The histological findings of BPOP are similar to those of florid reactive periostitis (FRP) and subungual (Dupuytren's) exostosis. Some authors have postulated that all of these conditions are reactive proliferative lesions representing different phases of reactive processes. Whether BPOP is a reactive proliferative lesion or a neoplastic lesion, however, remains controversial. Recently, a t(1;17)(q32;q21) translocation in BPOP was detected using chromosome banding and fluorescence in situ hybridization (FISH) analyses. Here, we describe a 39-year-old Japanese female with BPOP arising in the proximal phalanx of her third toe. A cytogenetic analysis revealed a t(1;17)(q 42;q23) translocation. The breakpoints in this case are located close to those of previously reported cases. These results suggest that t(1;17) is a distinct translocation of BPOP and that BPOP is a neoplastic lesion, rather than a reactive proliferative process.


Subject(s)
Bone Neoplasms/genetics , Chromosomes, Human, Pair 17/genetics , Chromosomes, Human, Pair 1/genetics , Osteochondroma/genetics , Translocation, Genetic , Adult , Bone Neoplasms/pathology , Bone Neoplasms/surgery , Cell Proliferation , Disease-Free Survival , Female , Humans , In Situ Hybridization, Fluorescence , Osteochondroma/pathology , Osteochondroma/surgery , Radiography , Spectral Karyotyping , Toes/diagnostic imaging , Toes/pathology , Treatment Outcome
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