Simple modified silicone rubber injection technique in fresh cadaveric pelvis and extremities.

The silicone rubber injection technique was first described in 1999 and has been used in the vascular study of neurology and head and neck dissection. Silicone rubber is durable, flexible, and inexpensive. However, the original silicone rubber injection formula perfuses poorly into the pelvis and extremities. We present a simple modification to the silicone rubber injection technique, showcasing its effectiveness in studying the vascular structures in the pelvis and extremities. We used an ordinary mold-making silicone rubber. The new formula involves mixing the silicone rubber with silicone thinner, acetone, catalyst, and resin color. The mixture is then injected into the artery until the color becomes visible under the skin. The specimen is left at room temperature for 0.5-1 h for the silicone rubber to harden. With our technique, the silicone rubber substance perfuses adequately into small arterial perforators and can penetrate into the subdermal plexus. The smallest subdermal arteries identified under a light microscope measured 6 µm. The modified silicone rubber injection technique has proven to be a valuable tool in anatomical education and surgical training.

Establishment, characterization, and genetic profiling of patient-derived osteosarcoma cells from a patient with retinoblastoma.

Osteosarcoma is the most common malignant bone cancer in pediatric patients. Patients who respond poorly to chemotherapy experience worse clinical outcomes with a high mortality rate. The major challenge is the lack of effective drugs for these patients. To introduce new drugs for clinical approval, preclinical studies based on in vitro models must demonstrate the potency of the tested drugs, enabling the drugs to enter phase 1 clinical trials. Patient-derived cell culture is a promising testing platform for in vitro studies, as they more accurately recapitulate cancer states and genetic profiles compared to cell lines. In the present study, we established patient-derived osteosarcoma cells (PDC) from a patient who had previously been diagnosed with retinoblastoma. We identified a new variant of a germline mutation in the RB1 gene in the tissue of the patient. The biological effects of this PDC were studied to observe whether the cryopreserved PDC retained a feature of fresh PDC. The cryopreserved PDC preserved the key biological effects, including cell growth, invasive capability, migration, and mineralization, that define the conserved phenotypes compared to fresh PDC. From whole genome sequencing analysis of osteosarcoma tissue and patient-derived cells, we found that cryopreserved PDC was a minor population in the origin tissue and was selectively grown under the culture conditions. The cryopreserved PDC has a high resistance to conventional chemotherapy. This study demonstrated that the established cryopreserved PDC has the aggressive characteristics of osteosarcoma, in particular the chemoresistance phenotype that might be used for further investigation in the chemoresistant mechanism of osteosarcoma. In conclusion, the approach we applied for primary cell culture might be a promising method to generate in vitro models for functional testing of osteosarcoma.

Can conventional magnetic resonance imaging at presentation predict chemoresistance in osteosarcoma?

OBJECTIVES: Histological tumour necrosis is the current indicator for the response of osteosarcoma after neoadjuvant chemotherapy. Chemoresistant tumours require close monitoring and adjustment of treatment. Characteristics of tumours on baseline MRI may be able to predict response to chemotherapy. The aim is to identify which baseline MRI findings can help predict chemoresistant osteosarcoma. METHODS: Baseline MRI before giving neoadjuvant chemotherapy of 95 patients during 2008-2021 was reviewed by 2 musculoskeletal radiologists. Histological necrosis from surgical specimens was the reference standard. MRIs were reviewed for tumour characteristics (tumour volume, maximum axial diameter, central necrosis, haemorrhage, fluid-fluid level), peritumoural bone and soft tissue oedema, and other parameters including intra-articular extension, epiphyseal involvement, neurovascular involvement, pathologic fracture, and skip metastasis. The cut-off thresholds were generated by receiver operating characteristic curves which then tested for diagnostic accuracy. RESULTS: Two-third of patients were chemoresistance (histological necrosis <90%). Tumour volume >150 mL, maximum axial diameter >7.0 cm, area of necrosis >50%, presence of intra-articular extension, and peritumoural soft tissue oedema >6.5 cm significantly predicted chemoresistance, particularly when found in combination. Tumour volume >150 mL and maximum axial diameter >7.0 cm could be used as an independent predictor (multivariable analysis, P-value = .025, .045). CONCLUSIONS: Findings on baseline MRI could help predicting chemoresistant osteosarcoma with tumour size being the strongest predictor. ADVANCES IN KNOWLEDGE: Osteosarcomas with large size, large cross-sectional diameter, large area of necrosis, presence of intra-articular extension, and extensive peritumoural soft tissue oedema were most likely to have a poor response to neoadjuvant chemotherapy.

Characterization of Cell-Free DNA Size Distribution in Osteosarcoma Patients.

PURPOSE: Cell-free DNA (cfDNA) analysis is a powerful tool for noninvasively predicting patient outcomes. We analyzed the size distribution of cfDNA and assessed its prognostic and diagnostic values in an osteosarcoma cohort. EXPERIMENTAL DESIGN: The fragment size distribution and level of cfDNA were analyzed in 15 healthy donors and 50 patients with osteosarcoma using automated capillary electrophoresis. The prognostic performance of cfDNA size analysis was assessed using univariate and multivariable analyses. By performing whole-genome sequencing of matched cfDNA and osteosarcoma tissue samples, we investigated the correlation between the size and mutation profiles of cfDNA and the mutation concordance between cfDNA and paired tissue tumors. RESULTS: The size of cfDNA fragments in patients with osteosarcoma was significantly shorter than in healthy donors, with the integrative analysis of size distribution and level of cfDNA achieving a high specificity and sensitivity of 100%. The short cfDNA fragment (150-bp cut-off) was an independent prognostic predictor in this osteosarcoma cohort [HR, 9.03; 95% confidence interval (CI), 1.13-72.20; P = 0.038]. Shortened cfDNA fragments were found to be a major source of mutations. Enrichment of cfDNA fragments with less than or equal to 150 bp by in silico size selection remarkedly improved the detection of copy-number variation signals up to 2.3-fold when compared with total cfDNA, with a higher concordance rate with matched osteosarcoma tissue. CONCLUSIONS: This finding demonstrated the potential of cfDNA size profiling in the stratification of poor prognostic patients with osteosarcoma. The short fragments of cfDNA are a promising source for boosting the detection of significant mutations in osteosarcoma. See related commentary by Weiser et al., p. 2017.

Potential target identification for osteosarcoma treatment: Gene expression re-analysis and drug repurposing.

Survival rate of osteosarcoma has remained plateaued for the past three decades. New treatment is needed to improve survival rate. Drug repurposing, a method to identify new indications of previous drugs, which saves time and cost compared to the de novo drug discovery. Data mining from gene expression profile was carried out and new potential targets were identified by using drug repurposing strategy. Selected data were newly categorized as pathophysiology and metastasis groups. Data were normalized and calculated the differential gene expression. Genes with log fold change ≥ 2 and adjusted p-value ≤ 0.05 were selected as primary candidate genes (PCGs). PCGs were further enriched to determine the secondary candidate genes (SCGs) by protein interaction analysis, upstream transcription factor and related-protein kinase identification. PCGs and SCGs were further matched with gene targeted of corresponding drugs from the Drug Repurposing Hub. A total of 778 targets were identified (360 from PCGs, and 418 from SCGs). This newly identified KLHL13 is a new candidate target based on its molecular function. KLHL13 was upregulated in clinical samples. We found 256 drugs from matching processes (50anti-cancerand206non-anticancerdrugs). Clinical trials of anti-cancer drugs from 5 targets (CDK4, BCL-2, JUN, SRC, PIK3CA) are being performed for osteosarcoma treatment. Niclosamide and synthetic PPARÉ£ ligands are candidates for repurposing due to the possibility based on their mechanism and pharmacology properties. Re-analysis of gene expression profile could identify new potential targets, confirm a current implication, and expand the chance of repurposing drugs for osteosarcoma treatment.

A Case of Infantile Hepatic Hemangioendothelioma/Hemangioma at Maharaj Nakorn Chiang Mai Hospital.

Infantile hepatic hemangioendothelioma/hemangioma is the most common benign hepatic vascular tumor of infancy, comprising approximately 1% of all childhood tumors. The tumor can present during the fetal or neonatal period as a hepatic mass. Common presentations include abdominal distension and a palpable hepatic mass. Clinico-radio-pathological correlation is essential for a definite diagnosis. Frequent complications such as congestive heart failure, thrombocytopenia, anemia, and Kasabach-Merritt syndrome should be investigated. Chemotherapy has been reported as an effective treatment option. Surgical resection has an essential role for symptomatic patients with medical treatment failure or other certain conditions such as refusal to take medication. Furthermore, prenatal diagnosis is essential for better patient outcomes due to prompt treatment in the neonatal period. We report a case of a female infant at 39 weeks of gestation who was delivered from a 32-year-old mother. The infant was in utero diagnosed by ultrasonography with a hepatic mass, most likely hemangioma. The mass was resected after birth and it was diagnosed as infantile hepatic hemangioendothelioma type II. The course of the disease was excellent and the patient was cured after treatment.

Relationship Between O-GlcNAcase Expression and Prognosis of Patients With Osteosarcoma.

Several studies have demonstrated a role of O-GlcNAcylation (O-GlcNAc) in tumorigenesis of various carcinomas by modification of tumor-associated proteins. However, its implication in the pathogenesis of osteosarcoma remains unclear. This study aimed to investigate the levels of O-GlcNAc and the expressions of O-linked N-acetylglucosamine transferase (OGT) and O-GlcNAcase (OGA) in human osteosarcoma tissues, by using immunohistochemistry; and to find correlations between the levels or expressions and several clinicopathologic parameters. There were 109 first diagnosed osteosarcoma patients, including Enneking stage IIB (n=70) and III (n=39). Correlations between the immunoreactive score (IRS) and clinicopathologic parameters, overall survival, and metastasis-free survival were evaluated. A positive correlation was found between the IRS of OGA and the percentage of postchemotherapeutic tumor necrosis (r=0.308; P=0.017). Univariate analysis revealed significantly lower OGA IRS in metastatic patients (P=0.020) and poor chemotherapeutic-responder patients (P=0.001). By multivariate analysis, presence of tumor metastasis (P=0.002) and lower OGA IRS (P=0.004) was significantly associated with shorter overall survival. Subgroup analysis in stage IIB osteosarcoma (n=70) demonstrated that male sex (P=0.019), presence of tumor recurrence (P=0.026), poor chemotherapeutic responder (P=0.022), and lower OGA IRS (P=0.019) were significantly correlated with short metastasis-free survival. But, lower OGA IRS was the only independent predictor for short metastasis-free survival (P=0.006). Our findings suggested that O-GlcNAc pathway, especially OGA, may involve in pathogenesis and aggressiveness of osteosarcoma. Low level of OGA expression may be used as a poor prognostic indicator.

IMPDH2 and HPRT expression and a prognostic significance in preoperative and postoperative patients with osteosarcoma.

Osteosarcoma is one of the most aggressive bone tumors in children and adolescents. Development of effective therapeutic options is still lacking due to the complexity of the genomic background. In previous work, we applied a proteomics-guided drug repurposing to explore potential treatments for osteosarcoma. Our follow-up study revealed an FDA-approved immunosuppressant drug, mycophenolate mofetil (MMF) targeting inosine-5'-phosphate dehydrogenase (IMPDH) enzymes, has an anti-tumor effect that appeared promising for further investigation and clinical trials. Profiling of IMPDH2 and hypoxanthine-guanine phosphoribosyltransferase (HPRT), key purine-metabolizing enzymes, could deepen understanding of the importance of purine metabolism in osteosarcoma and provide evidence for expanded use of MMF in the clinic. In the present study, we investigated levels of IMPDH2, and HPRT in biopsy of 127 cases and post-chemotherapy tissues in 20 cases of high-grade osteosarcoma patients using immunohistochemical (IHC) analysis. Cox regression analyses were performed to determine prognostic significance of all enzymes. The results indicated that low levels of HPRT were significantly associated with a high Enneking stage (P = 0.023) and metastatic status (P = 0.024). Univariate and multivariate analyses revealed that patients with low HPRT expression have shorter overall survival times [HR 1.70 (1.01-2.84), P = 0.044]. Furthermore, high IMPDH2/HPRT ratios were similarly associated with shorter overall survival times [HR 1.67 (1.02-2.72), P = 0.039]. Levels of the enzymes were also examined in post-chemotherapy tissues. The results showed that high IMPDH2 expression was associated with shorter metastasis-free survival [HR 7.42 (1.22-45.06), P = 0.030]. These results suggest a prognostic value of expression patterns of purine-metabolizing enzymes for the pre- and post-chemotherapy period of osteosarcoma treatment.

Effects of type II SLAP lesion repair techniques on the vascular supply of the long head of the biceps tendon: a cadaveric injection study.

BACKGROUND: One option for the treatment of type 2 superior labral anterior to posterior (SLAP) lesions is arthroscopic repair. However, the fact that the vascular supply of the proximal long head of the biceps tendon (LHBT) arises from the soft tissue near the SLAP repair site must also be considered. The aims of this study were to evaluate the vascular channel of the proximal long head biceps tendon and to compare potential damage to the vascular supply with alternative SLAP techniques. METHODS: Forty-five fresh cadaveric shoulders were divided into 3 groups: 9 shoulders each for the normal group and the created SLAP group, and 27 shoulders for the repaired SLAP group. SLAP group shoulders were repaired using one of 3 techniques: 2 anchors with simple sutures, 1 anchor with double sutures, or 1 anchor with a horizontal mattress suture. India ink was then injected into the acromial branch of the thoracoacromial artery. The proximal LHBT was resected for a histologic cross-sectional study. The intratendinous vascular distance was measured and compared among the groups. RESULTS: The vascular supply of the proximal LHBT arises from soft tissue lying anterior and dorsal to the tendon origin. In the normal shoulders, the average intratendinous vascular distance was 16.9 ± 1.5 mm (95% confidence interval: 15.8-18.1). A comparison of nonrepaired SLAPs with each of the repair techniques found that using 2 anchors with simple sutures showed no significant difference in vascular distance (P = .716), whereas the other techniques showed a significant disruption of the blood supply. The differences in vascular distance among the 3 repair techniques were statistically significant (P = .0001). CONCLUSIONS: The main vascular supply of the proximal LHBT comes from the anterior-dorsal direction. Some SLAP repair techniques can disrupt vascularization; however, the technique using 2 anchors with simple sutures, 1 anchor 3 mm anterior to the anterior border and 1 at the posterior border of the tendon, can preserve the vascularization of the LHBT.

Expression profiling of DNA methyl transferase I (DNMT1) and efficacy of a DNA-hypomethylating agent (decitabine) in combination with chemotherapy in osteosarcoma.

BACKGROUND: Abnormality in the DNA methylation process is one of the hallmarks of cancer. Emerging evidence strongly supports the idea that defects in DNA methyl transferases (DNMTs) are involved in tumor development and progression. This alteration has major effects at the transcription level of various cancer-associated genes. METHODS: Expression profiles of DNMT1 were investigated in fresh frozen tissues, patient-derived cells, and formalin-fixed paraffin-embedded tissues using immunoblotting and immunohistochemistry analysis. We also examined an anti-tumor effect of single DNA-hypomethylating agent (decitabine) and a combination of decitabine and chemotherapy in osteosarcoma cell lines. RESULTS: The results showed an overexpression of DNMT1 in most cases compared to normal cells and tissue samples. DNMT1 was also expressed at the same levels in paired primary cells derived from biopsy and post-chemotherapy tissues. Expression patterns of DNMT1 were examined in 77 osteosarcoma patients of whom 82% had positive DNMT1 with an IRS score > 0. Most of the cases expressed low to moderate levels of DNMT1 (IRS range 1-8, median = 2.0). Furthermore, we found that a combination of decitabine and chemotherapy had a synergistic effect in most of the tested osteosarcoma cells at a low dose therapeutic range of decitabine. CONCLUSIONS: Our study revealed DNMT1 expression patterns that indicated potential roles of DNMT1 in osteosarcoma transformation and progression. This finding also suggests the efficacy of a combination therapy of decitabine with chemotherapy for osteosarcoma treatment.

In vitro drug sensitivity (IDS) of patient-derived primary osteosarcoma cells as an early predictor of the clinical outcomes of osteosarcoma patients.

PURPOSE: Early prediction of clinical response to conventional chemotherapy is a significant factor in determining an overall treatment strategy for osteosarcoma. METHODS: Cells were extracted from treatment-naïve biopsies from 16 osteosarcoma patients who received a doxorubicin and cisplatin-based neoadjuvant chemotherapy regimen and their sensitivities to doxorubicin and cisplatin were measured as IC50 values. Associations of in vitro drug sensitivity (IDS) levels and clinical outcomes were examined. RESULTS: Primary osteosarcoma cells responded to doxorubicin and cisplatin with IC50 values of 0.088 ± 0.032 µM and 16.7 ± 8.5 µM, respectively. The patients with a non-metastatic phenotype and surviving patients showed significantly lower IC50 values for both drugs. ROC analysis defined the optimal IC50 cut-off values for doxorubicin (IDSdox) and cisplatin (IDScpt) as 0.05 µM (AUC 0.82) and 14 µM (AUC 0.87), respectively. Survival analysis found significantly longer disease-free survival (DFS, n = 14) and overall survival (OS, n = 16) times in the patients with low IDSdox (p = 0.0064 for DFS and p = 0.0102 for OS) and low IDScpt (p = 0.0204 for DFS and p = 0.0021 for OS). Interestingly, when the patients with low IDScpt and those with low IDSdox were combined (Group 1), significant associations with prolonged DFS (p = 0.0042, C-statistic 0.78) and OS (p = 0.0010, C-statistic 0.79) were found. In this cohort, histological response to neoadjuvant chemotherapy could predict only OS. CONCLUSIONS: This study indicates that IDS analysis could potentially be a practical, rapid, and reliable technique for predicting clinical outcomes. It could also be used to identify patients for whom conventional chemotherapy is most appropriate and, in the future, help advance personalized therapy.

Mycophenolic acid is a drug with the potential to be repurposed for suppressing tumor growth and metastasis in osteosarcoma treatment.

Our previous review of proteomics data showed that in osteosarcoma, some overexpressed proteins were targets of FDA-approved immunosuppressive and anti-arrhythmic drugs, including mycophenolate mofetil (MMF), ribavirin, leflunomide, azathioprine and digoxin. Here, these drugs were screened for growth inhibitory effects in human osteosarcoma cell lines, including MNNG/HOS, U2OS, SaOS-2, MG-63 and 143B cells. Only mycophenolic acid (MPA), an active metabolite of MMF, efficiently inhibited osteosarcoma cell growth with IC50 values of 0.46-7.3 µM; these values are in the therapeutic range for organ transplant patients. At a therapeutic dose (10 µM), MPA significantly inhibited colony formation, caused cell cycle arrest in the S phase, and induced apoptosis. Moreover, the in vitro invasion of osteosarcoma cells was reduced by MPA by inhibiting cell migration capability. The in vivo antitumor effect of MMF was determined in nude mice harboring 143B cell xenografts. Daily oral administration of 200 mg/kg/day MMF for 2 weeks significantly suppressed tumor growth in treated mice, achieving 57.4 ± 11.1% tumor growth inhibition. Compared with the vehicle group, the MMF group treated with 50-200 mg/kg/day for 3 weeks had a significant reduction in the number of lung metastatic nodules in a tail vein-lung metastasis model of 143B cells. MMF doses of 50, 100 and 200 mg/kg/day are approximately equivalent to the non-toxic doses of 0.25, 0.5 and 1 g/day in humans, respectively. These findings indicate that MPA/MMF can effectively control osteosarcoma tumor growth and metastasis. Thus, the potential to repurpose MPA/MMF for use in osteosarcoma chemotherapy is of great interest.

Endoplasmic reticulum protein 29 (ERp29) as a novel prognostic marker and tumor suppressor in osteosarcoma.

BACKGROUND: Diverse aberrancy in genetic background, protein profiling, and biological pathways have emerged as important factors hindering discovery of effective treatment of osteosarcoma. In a previous study, we used a proteomic approach to identify some osteosarcoma-related proteins by analysis of protein profiling in individual patients through primary cell culture. Endoplasmic reticulum protein 29 (ERp29) emerged as a protein of interest for further study since accumulating evidence suggests it has broad functions in tumorigenesis of different types of cancer. Importantly, until now no report on examination of the expression patterns of ERp29 in osteosarcoma has been published. METHODS: In this study, an expression of ERp29 was examined in patient-derived osteosarcoma cells (7 cases) and normal bone graft-derived osteoblasts (7 cases) using western blotting. Expression profile of ERp29 in 94 osteosarcoma cases was investigated using immunohistochemically stained on formalin-fixed paraffin-embedded biopsied tissue. An association with clinicopathologic parameters and the patient survival was evaluated. The doubling time of five osteosarcoma cells lines expressing different levels of ERp29 was determined by a cell number along the exponential phase of the growth curve. RESULTS: The results substantiate the outcome from the proteomic study in which ERp29 expression was significantly higher in primary osteosarcoma cells compared to osteoblastic cells. Immunohistochemical analysis found that expression of ERp29 was low in 79% of the cases (immunoreactive score (IRS) <6). A significant correlation was observed between expression of ERp29 and patient survival. Lower expression of ERp29 (IRS<6) was statistically significantly associated with shorter overall survival of the patients (P = 0.041). In addition, we found that osteosarcoma cells with low ERp29 expression had a higher growth rate compared with high-ERp29-expressing cells. CONCLUSIONS: These findings suggest a tumor suppressive role of ERp29 in osteosarcoma. In addition, ERp29 might potentially be applied as a prognostic indicator in patients with osteosarcoma.

Protein profiling of osteosarcoma tissue and soft callus unveils activation of the unfolded protein response pathway.

Oncogenic drivers of osteosarcoma remain controversial due to the complexity of the genomic background of the disease. There are limited novel therapeutic options, and the survival rate of patients with osteosarcoma has not improved in decades. Genomic instability leads to complexity in various pathways, which is potentially revealed at the protein level. Therefore, the present study aimed to identify the mechanisms involved in the oncogenesis of osteosarcoma using proteomics and bioinformatics tools. As clinical specimens from patients are the most relevant disease­related source, expression patterns of proteins in osteosarcoma tissues were compared with soft tissue callus from donors containing high numbers of osteoblastic cells. Two­dimensional electrophoresis and liquid chromatography­tandem mass spectrometry (LC­MS/MS) successfully identified 33 differentially expressed proteins in the osteosarcoma tissues compared with the soft tissue callus. Among these proteins, 29 proteins were significantly upregulated in osteosarcoma. A functionally grouped network of the overexpressed proteins, that was created using the ClueGo and CluePedia applications, demonstrated that the unfolded protein response (UPR) pathway was activated mainly through the activating transcription factor 6 arm in osteosarcoma. The results of proteomics analysis were confirmed by elevated expression of UPR­related chaperone proteins, including 78 kDa glucose­related protein (GRP78), endoplasmin, calreticulin and prelamin­A/C, in the patient­derived primary cells and osteosarcoma cell lines. Furthermore, the expression of GRP78, a master regulator of the UPR, was enhanced in the osteosarcoma tissues of patients that were resistant to double regimen of doxorubicin and a platinum­based drug. The findings of the present study suggest that targeting the UPR pathway may be promising for the treatment of osteosarcoma.

Oncogenic roles of serine-threonine kinase receptor-associated protein (STRAP) in osteosarcoma.

PURPOSE: To validate the presence of serine-threonine kinase receptor-associated Protein (STRAP) in osteosarcoma tissue and to investigate the oncological role of STRAP in osteosarcoma. METHODS: Expression of STRAP protein in osteosarcoma tissue compared to soft callus (hyperactive bone healing tissue) and in multiple cell lines was examined using western blot analysis. Effects of STRAP silencing on cell proliferation, invasion, migration and re-implantability in chick chorioallantoic membrane (CAM) were observed in osteosarcoma cell lines (MNNG-HOS, 143B, and U2OS). RESULTS: The result demonstrated that STRAP was highly up-regulated in osteosarcoma tissues compared with the normal physiological bone healing tissue (soft callus). Expression level of STRAP was markedly high in osteosarcoma cell lines with aggressive phenotype. Upon STRAP silencing, invasion and migration, but not proliferative activity, were selectively modulated in high-expression-STRAP cell lines. In addition, STRAP silencing reduced the success rate of tumor implantation and growth of MNNG-HOS cells in CAM model. CONCLUSIONS: Serine-threonine kinase receptor-associated protein is up-regulated during osteosarcoma progression. The presence of STRAP enhances osteosarcoma cell invasion, migration and re-implantation ability, factors which play a critical role in metastasis. Serine-threonine kinase receptor-associated protein and its related pathway are worthy for further exploration as a novel target for anti-metastasis agents.

Aorto-enteric Fistula After Endovascular Abdominal Aortic Aneurysm Repair for Behcet's Disease Patient: A Case Report.

INTRODUCTION: A 42 year old male with Behcet's disease (BD) had endovascular treatment of a symptomatic infrarenal abdominal aortic aneurysm (AAA). Thirteen months later he developed haematemesis and melaena. METHODS: Computed tomography (CT) and angiography showed an aorto-enteric fistula with migration and kinking of the stent graft. Explantation of the infected graft and axillobifemoral bypass, aneurysm sac debridement, and jejunal repair with omental interposition was performed on this severely contaminated patient. DISCUSSION: There are no reports of an aorto-enteric fistula secondary to endovascular repair in the literature and this case describes the potential consequences of endovascular repair of AAA in BD. The aorto-enteric fistula was associated with persistent inflammatory aortitis, stent graft kinking, and infection. Five cases of secondary aorto-enteric fistulas following open AAA repair in BD patients have been reported including this case resulting from endovascular repair.

Prognostic score for life expectancy evaluation of lung cancer patients after bone metastasis.

BACKGROUND: This study identifies the overall survival status of lung cancer patients with bone metastasis and metastasis patterns. Poor prognostic factors were identified to develop a scoring system for estimating survival period after bone metastasis. METHODS: A retrospective cohort analysis was performed at Chiang Mai University for the period January 1, 2006 and December 31, 2013. Time-to-event analysis was performed to estimate survival rate. The primary end point was death related to lung cancer. Univariate and multivariate analysis of the prognostic variables was done using the Cox's regression model. The score was derived from the corresponding estimated regression coefficients of significantly poor prognostic factors. RESULTS: A total of 505 lung cancer with bone metastasis patients were analyzed. Four hundred two cases (79.6%) were concurrent diagnosis and 103 (20.4%) were subsequent diagnosis. The median survival time of lung cancer after bone metastasis 148 days. Male gender and ECOG 3-4 were significant poor prognostic factors for lung cancer after bone metastasis, with hazard ratios of 1.42 (95% CI 1.17-1.73), and 1.30 (95% CI 1.06-1.60), respectively. Prognosis score was determined using the binary term present/not-present for those factors. The curve from prognostic score summations of 2, 1 and 0 presented a good discrimination of survival expectancy, showing an expected median survival time of approximately 109, 146, and 225 days, respectively. CONCLUSIONS: Prognostic score is a clinically simple and easy method for estimating life expectancy and for guiding interventions in bone metastasis of lung cancer.

Expression patterns of class I histone deacetylases in osteosarcoma: a novel prognostic marker with potential therapeutic implications.

Epigenetic aberrations are recognized as having pivotal roles in cancer etiology and progression. Histone deacetylases are among the most studied epigenetic modulators in various cancer types. The expression levels of class I histone deacetylase isoforms 1, 2, and 3 in patient-derived primary osteosarcoma cells (6 cases) was investigated, comparing them to normal bone graft-derived osteoblasts (6 cases) using the immunoblotting technique. Expression profiles of histone deacetylases in high-grade osteosarcoma tissue of 89 patients were examined and their association with clinicopathologic parameters and the patient survival was evaluated. Histone deacetylases were immunohistochemically stained on formalin-fixed paraffin-embedded biopsied tissue. Primary osteosarcoma cells expressed higher levels of histone deacetylase 1 and histone deacetylase 2, but lower levels of histone deacetylase 3 compared to benign osteoblasts. Overall, 82, 99, and 93% of 89 osteosarcomas showed nuclear expression of the histone deacetylase isoforms 1, 2, and 3, respectively. Low levels of histone deacetylase 1 were significantly associated with a high Enneking stage (P=0.014) and the presence of initial metastasis (P=0.040), while low levels of histone deacetylase 3 were significantly correlated with age >15 years (P=0.026). Univariate survival analysis found significantly shorter survival in the patients with a high Enneking stage (P<0.001), axial location (P=0.009), presence of initial metastasis (P<0.001), low-histone deacetylase 1 expression (P=0.038), and low-all-histone deacetylases expression (P=0.016). Multivariate survival analysis showed that only axial location (P=0.011) and low-all-histone deacetylases expression (P=0.039) were independent prognostic factors. In subgroup analysis of stage IIB patients (n=45), only axial location and low-all-histone deacetylases expression were associated with shorter survival in both univariate and multivariate analysis (axial location, P=0.008 and 0.010; low-all-HDACs, P=0.013 and 0.038, respectively). Low levels of all-histone deacetylases expression were significantly associated with advanced disease status and short survival. These findings may be a guide to future use of histone deacetylase inhibitors in osteosarcoma patients.

Ankle ligament reconstruction after wide resection of the osteosarcoma of the distal fibula: a case report.

BACKGROUND: Restoration of the lateral ankle after distal fibulectomy is a difficult reconstructive procedure. Many surgical techniques have been proposed. This report shows another fibular reconstructive option with promising outcome. CASE PRESENTATION: We report the case of a 30-year-old woman who presented with a solitary mass located in the lateral aspect of the ankle. The mass had grown rapidly for 2 months and caused increasing pain. Physical examination showed a 3.0 cm diameter tender, nonmobile hard mass in the lateral malleolus. Radiographs showed an osteolytic lesion involving the lateral cortex at the distal fibula. After incisional biopsy, pathologic examination found a well-differentiated intramedullary osteosarcoma. Neoadjuvant chemotherapy with doxorubicin was provided for 3 months prior to definitive surgical treatment. Magnetic resonance imaging showed persistent tumor in the biopsy site. After distal fibulectomy and wide resection, split tibialis posterior tendon transfer to the remaining peroneus brevis restored the stability of the ankle. The pain resolved within 3 months. The ankle was stable and no recurrence of the cancer was found at a 7 year follow-up. CONCLUSION: Reconstruction following distal fibulectomy and surrounding soft tissue resection responds favorably to split tibialis posterior transfer to the remaining peroneus brevis suggesting that this technique can provide a good and functional outcome.

Spindle Cell Hemangioma of the Midfoot: A Case Report.

INTRODUCTION: Spindle cell hemangioma (SCH) of the bone (midfoot) is a rare disease, but it can cause symptomatic pain and invade surrounding tissues lead to limb deformities and functional loss. CASE REPORT: We report the case of a 35-year-old woman who experienced a firm mass over the left midfoot for 5 years causing pain and numbness in the foot. Radiographs showed a geographic osteolytic lesion involving calcification of the base of the 2nd and 3rd metatarsals, cuneiforms bones and surrounding soft tissue. Magnetic resonance imaging revealed a lobulated mass in the midfoot containing tangles of tortuous blood vessels and dark foci characteristic of phleboliths. Wide resection of the 2nd and 3rd cuneiforms, metatarsal bones and surrounding tissues with a curved iliac bone graft reconstruction were performed. Histological assessment revealed a lesion composed of a vascular channel containing endothelial cells with smooth muscle but without cellular atypia. The definite diagnosis was spinal cell hemangioma. The pain resolved within 4 months. The foot was stable, and no recurrence was found at the 48 months follow-up. CONCLUSION: This unusual disease, SCH of the midfoot responded favorably to wide resection and curved iliac bone grafting. It is suggested that this approach will provide a satisfactory functional result.