Surgical Treatment of Pathologic Humeral Fracture

PURPOSE: To evaluate and analyze the radiographic and clinical outcomes after the surgical treatments of pathologic humeral fractures. MATERIALS AND METHODS: From October 1993 to September 2007, a retrospective investigation was conducted with a total of 13 patients who underwent operations for pathologic humeral fractures. The methods of surgical treatment were as follows-four cases of open reduction and internal fixation; eight cases of closed reduction and internal fixation with intramedullary nailing; and one of radical excision and hemiarthroplasty. RESULTS: Of nine patients with metastatic bone lesions, three were diagnosed with primary cancer after the incidence of pathologic humeral fracture. The mean period between the diagnosis of primary cancer and pathologic fracture in the latter six cases was 36.7 (2~144) months and the mean survival period after the surgical treatments was 22.8 (12~35) weeks in all patients with bone metastasis. Fracture unions were noted in all four cases of primary humeral bone lesion but none in metastatic cases. Pain relief and functional recovery were noted in eleven patients of this study. CONCLUSION: Satisfactory clinical outcomes with sustained pain relief and functional recovery were observed after the surgical treatments of pathologic humeral fracture. Benign bone lesions require more active and early treatments in order to facilitate the functional recovery of upper extremities and fracture union. With pathologic humeral fractures originated from metastasis, palliative treatments were preferred to fracture union method for planning long-term pain relief and functional recovery.

The Control of Tumor Cell Invasiveness in Chondrosarcoma Cell Lines by Modifying Focal Adhesion Kinase Expression / 대한정형외과학회잡지

PURPOSE: We propose that cell attachment and invasion can be regulated by the modulation of FAK expression in chondrosarcoma cell lines. MATERIALS AND METHODS: The C-terminal domain of FAK (FAK-CD) was transfected by recombinant adenovirus infection in chondrosarcoma cell lines, JJ012 and 105KC. The expression of FAK, FAK-CD and tyrosine phosphorylation were checked. Chondrocytes and chondrosarcoma cells were used in cell attachment tests by blocking or not blocking integrin-beta 1 antibodies and synthetic peptides on type II collagen. To evaluate the effect of cell invasiveness, a wound healing assay and a Boyden chamber assay were done after FAKCD transfection. RESULTS: We observed higher FAK expression in the chondrosarcoma cells than in chondrocytes. The level of attachment to type II collagen was significantly inhibited by blocking with the antibody of integrin-beta 1 and synthetic RGD peptides. Also, the adenovirus mediated transfection of FAK-CD resulted in the inhibition of the phosphorylation of FAK and significant inhibition of cell attachment in only JJ012, without changing FAK expression. Moreover, migration after transfection with FAK-CD was reduced by up to 79.9% for JJ012 and 75.5% for 105KC. CONCLUSION: Attachment of chondrosarcoma cells could be mediated through integrin-beta 1. We conclude that modified FAK expression contributes to the suppression of tumor cell attachment and invasion.

The control of chondroid cell's adhesiveness by modulation of focal adhesion kinase(FAK) expression / 대한정형외과연구학회지

PURPOSE: We propose that cell attachment can be regulated by the modulation of FAK expression using an adenovirus vector. MATERIALS AND METHODS: Chondrocytes and chondroid cells were used in cell attachment test by blocking or non-blocking of antibodies and synthetic peptides on type II collagen precoated 96-well immunoplates. The C-terminal domain of FAK(FAK-CD) was transfected through infection of the recombinant adenovirus. Also tyrosine phosphorylation of FAK was checked by immunoprecipitation of FAK followed by western blot analysis with anti-phosphotyrosine antibody. For evaluating the change of integrin expression, semi-quantitative reverse-transcription polymerase chain(RT-PCR) reactions were done after transfection of FAK-CD. RESULTS: We observed more increased expression of FAK in the chondroid cells than that in chondrocytes using western blotting. The level of attachment to type II collagen was significantly inhibited by blocking with the monoclonal antibody of integrin-beta1 and synthetic RGD peptides. Also adenovirus mediated transfection of FAK-CD resulted in inhibition of phosphorylation of FAK and significantly inhibited cell attachment in only JJ102. Integrin-beta1 antibody blocking after transfection with FAK-CD showed inhibition of cell attachment in more than 95% of all cells. The mRNA expression of both Integrin a2 and integrin a5 was increased but was not significant. Protein expression of integrin a2 and integrin a5 showed no changes. CONCLUSION: We found that the attachment of FAK-overexpressing cells could be mediated through integrin-beta1 receptor. We concluded that the modification of FAK expression will contribute to increase the cell attachment to biomaterials and regeneration of cartilage defects.

Efficacy of Pre- and Postoperative Chemotherapy in Patients with Osteosarcoma of the Extremities / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: We evaluated the treatment efficacy including survival and recurrence, and factors associated with recurrence in osteosarcoma patients treated with preoperative chemotherapy, surgery, and adjuvant chemotherapy. MATERIALS AND METHODS: Forty nine patients with osteosarcoma were treated with preoperative chemotherapy with intra-arterial cisplatin and adriamycin infusion for 3 cycles, followed by surgery. According to the pathologic response, if tumor was necrotized more than 90%, the same adjuvant chemotherapy was reintroduced for 3 cycles, and if the response was not enough, then the salvage regimen was introduced. Plain chest film and chest CT scan were taken monthly and every 3 months, respectively. When tumor recurred, the metastasectomy was performed whenever possible. RESULTS: Forty three patients were evaluable with amedian follow up of 53 months. Five-year disease-free and overallsurvival rate was 47.0% and 66.9%, respectively. The recurrence was observed in 22 patients (51.2%) with median time of 12.5 months. Baseline alkaline phosphatase (ALP) was the only significant factor for recurrence (p=0.03) and the patients with the possibility of metastasectomy recurrence showed higher post-relapse survival compared to other treatment modalities (26 momths vs 5~12 months). CONCLUSION: These results indicates that pre- and postoperative chemotherapy with intra-arterial cisplatin and adriamycin infusion showed comparable treatment efficacy and acceptable toxicities.

Correlation of Laminated MR Appearance of Artcular Cartilage with Histology

PURPOSE: To determine the correlation of laminae of different signal intensities (SI) of articular cartilage,as seen on magnetic resonance (MR) imaging with histologic layes, using artificially constructed landmarks. MATERIALS AND METHODS: For a landmark that can exactly correlate the cartilage specimen with the MR image, five'V'-shaped markings of different depths were made on the surface of bovine patella. Both T1-weighted (TR/TE :300/14) and FSE T2-weighted images (TR/TE : 2000/53) were obtained on a 1.5T system with high gradient echostrength (25mT/m) and a voxel size of 78x78x2000 micrometer. Images were obtained with 1) changed frequency-encodingdirections on T1-weighted study, and 2) changed readout gradient strength (x2, x1/2) on T2-weighted sequence.Raw image data were transferred to a workstation and signal intensity profile was generated for each image. 1 : 1correlation of histologic specimens and MR images was performed. RESULTS: Line Profile through the cartilageshowed few peaks, suggesting changes in signal intensity profile in the cartilage. On the basis of artificiallandmarks, the histologic zone was accurately identified. The histologic tangential and transitional zonescorrelated with superficial high SI on T1WI, as well as high and low SII on T2WI. On T1WI, the radial zonecorrelated with a lamina of intermediate SI, and on T2WI, with a lamina for which SI gradually decreased from highto low. Additional well-defined low and intermediate SI bands were noted on bovine T1WI in the lower radial zone.In both T1 and T2 studies, calcified cartilage layers were of low SI. On T1-weighted study, changes in thedirection of frequency gradient did not lead to changes in the laminae. The alteration of readout gradientstrengths did not result in an inversely proportional difference in the thickness of the laminae. These becamemore distinct thus ruling out chemical shift and susceptibility artifacts. CONCLUSION: The laminated appearanceof articular cartilage, as seen on spin echo and fast spin-echo MR images, correlated with histologic layersrather than susceptibility or chemical shift artifacts.

The Efficacy of Pre - operative Chamotherapy with Intra-arterial Cisplatin and Intravenous Adriamycin for High Grade Osteosarcoma / 대한암학회지

PURPOSE: Osteosarcoma is one of the most common juvenile malignant tumors in Korea. Combined modality treatment [pre-operative chemotherapy + surgery (limb salvage or amputation) + adjuvant chemotherapy] had improved the overall survival and quality of life. To improve the local control rate, we introduced pre-operative chemotherapy combined with intra-arterial (IA) cisplatin and continuous intravenous infusion (CI) of adriamycin. We evaluated the efficacy and feasibility, such as limb salvage rate, recurrence pattern and the survival impact, based on the histologic response of pre-operative chemotherapy. MATERIALS AND METHODS: Fourty-one patients with histologically-proven high grade osteosarcoma of the extremities were enrolled from January 1990 to June 1996. Pre-operative chemotherapy, cisplatin 120 mg/m2 IA and adriamycin 75 mg/m2/72hrs CI, was administered for 3 cycles with 3 week interval, followed by surgery. Post-operative chemotherapy was applied by the tumor necrosis rate. If the tumor necrosis of the specimen was more than 90%, the same regimen af the preoperative one was administered for 3 cycles. A salvage regimen (Ifosfamide 7.5 gm/m2/5d IV + high dose MTX 10 gm/m2 IV VP-16 360 mg/m2/3d IV) was administered every 3 weeks for 6 cycles if the tumor necrosis was <90%. RESULTS: Of 41 patients, 37 were evaluable for efficacy and toxicities, because 4 refused further chemotherapy after 1 or 2 cycles. Twenty-one patients were male and 16 female, with the median age of 16 years (8-41). The tumor locations were as follows: distal femur 20, proximal tibia 8, humerus 6, distal tibia 2 and 1 in proximal femur. All but one patient, who died of neutropenic sepsis, completed the planned pre-operative therapy. Of the 36 patients who received surgery, limb salvage surgery was possible in 30 patients (83.3%) and 27 patients (75%) showed a good response (10 with grade III, 27.8%; 17 with grade IV, 47.2%). With a median follow-up of 23 months, 3-year disease-free survival rate was 54.7% and overall survival rate was 78.3%. Of the 15 patients who recurred, the major metastatic site was the lungs. No operation-related mortality was observed. Most patients experienced grade III-IV nausea, vomiting and hematologic toxicities, which were reversible with supportive care. CONCLUSION: Pre-operative chemotherapy combined with IA cisplatin and CI adriamycin induced higher good response rate without survival benefits. To improve the survival rate, the design of good salvage chemotherapy with a non-cross resistant regimen should be considered.

A Case of Osteosarcoma induced Oncogenic Osteomalacia Detected by MRI / 대한내분비학회지

Oncogenic osteomalacia is a syndrome characterized by phosphaturia, hypophosphatemia, decreased 1,25-dihydroxyvitamin D level and specific signs and symptoms of osteomalacia. It is associated with the presence of neoplasm originated from mesenchyme. Until now, less than 100 cases of oncogenic osteomalacia have been reported. The pathophysiology of oncogenic osteomalacia has not been fully understood, but it has been suggested that a certain substance released by tumor may inhibit not only la-hydroxylase activity and reduce 1,25-dihydroxyvitamin D level in part, but directly inhibit reabsorption of phosphate. And then, reduced phosphaturia, hypophosphatemia and eventually osteomalacia develop. We report a case of osteosarcoma induced oncogenic osteomalacia detected by MRI in 59 year old woman.