Metastatic disease of the long bones: a review of the health care burden in a major trauma centre

Background

More than 140 000 new cases of cancer are diagnosed annually in Canada, nearly half of which metastasize to bone. The implications for orthopedic oncology services are potentially huge. We reviewed the experience in a major Canadian orthopedic trauma centre treating long bone metastases. The primary aim was to quantify the caseload, and the secondary aim was to report on the methods of fixation.

Methods

We conducted a retrospective review of all patients treated for pathologic lesions or fracture secondary to metastatic disease over a 20-year period from July 1987 to March 2007.

Results

The mean number of cases treated annually was 13. Most patients came from the local oncology centre. The median length of stay in hospital was 11 days. Inhospital mortality was 14%. The fatal pulmonary embolus rate was 5% for femoral lesions. The revision rate for the operative intervention was 3%.

Conclusion

The caseload was much lower than anticipated, likely owing to under-referring from oncology services. The high mortality rate may reflect delay in seeking orthopedic opinion, but overall the fixation methods appeared durable.     

Conditioned media from human osteoarthritic synovium induces inflammation in a synoviocyte cell line

Aim: Osteoarthritis (OA) is a whole joint pathology involving cartilage, synovial membrane, meniscus, subchondral bone, and infrapatellar fat pad (IFP). Synovitis has been widely documented in OA suggesting its important role in pathogenesis. The aim of this study was to investigate the role of different joint tissues in promoting synovitis. Materials and methods: Conditioned media (CM) from cartilage, synovial membrane, meniscus, and IFP were generated from tissues of five patients undergoing total knee replacement and used to stimulate a human fibroblast-like synoviocytes cell line (K4IM). Cytokines, chemokines, and metalloproteases release was analyzed in all CM by Bio-Plex Assay and sulfated glycosaminoglycan (GAG) content by dimethylmethylene blue assay. Gene expression of several markers was evaluated by real-time PCR in K4IM cells stimulated with the CM obtained from joint tissues. Results: CM from all tissues produced high levels of IL-6, IL-8, and CCL2. CCL21, MMP-3, and ?13 levels were detected in all CM except IFP. MMP-10 was present only in CM of cartilage and synovial tissues. IL-1β, IL-15, TNF-α, CCL5, and CCL19 were undetectable. However, only K4IM cells stimulated by the CM from OA synovium showed an increase of IL-6, CXCL-8, CCL21, MMP10, and IL-1β expression. Conclusion: Our study showed that K4IM might be a suitable in vitro model for evaluating different cellular pathways in OA studies. Importantly, we demonstrated that in OA, all joint tissues might be involved in the progression of synovitis with a predominant role of synovial membrane itself compared to the other joint tissues.     

Overexpression of Hepatocyte growth factor and its soluble receptor (s-cMet) in the serum of patients with different grades of meningioma

ObjectivesMeningiomas are the most common primary intracranial tumor. Hepatocyte growth factor (HGF) and its receptor, cMet, were shown to be involved in meningioma. This study was aimed to determine the concentration of HGF and soluble cMet (s-cMet) in the serum of patients with different grades of meningioma.MethodsNinety serum samples from different grades of meningioma patients (42 cases of grade I, 28 grade II, 20 grade III) and 51 controls were included in this study. The serum total protein concentration (TPC) was measured by a Bio-Rad protein assay and serum concentration of HGF and s-cMet by enzyme linked immunosorbent assay (ELISA).ResultsNo significant change in the serum TPC of patients was seen as compared to controls. We also showed that serum HGF and s-cMet concentration in meningioma patients was higher than in controls. The results showed that starting from grades I to III meningioma, a significant increase in HGF and s-cMet serum concentration was observed (HGF; 380 ± 57.69, 430.27 ± 48.72, 596.36 ± 104.49 pg/ml, respectively, as compared to controls which was 327.72 ± 49.68 pg/ml and for s-cMet was 274.45 ± 45.05, 314.81 ± 38.71, 433.54 ± 51.81 ng/ml, respectively, as compared to controls which was 213.72 ± 29.13 ng/ml). The results showed that a high concentration of HGF and s-cMet is associated with advanced grades of meningioma.ConclusionIt is concluded that HGF and s-cMet serum levels increased in meningioma patients and their concentration was significantly higher in more advanced grades of the disease. It is also suggested that HGF/s-cMet might be involved in the progression of meningioma.     

Variations in the source of origin of inferior phrenic artery: a cadaveric study

Introduction: The right and left inferior phrenic arteries perfuse the diaphragm. They may originate either from the aorta, celiac trunk, or from the renal artery. Most textbooks of human anatomy give little information regarding the functional anatomy of the inferior phrenic artery. In the past few years, however, more articles have been published regarding the arterial supply in cases of hepatocellular carcinoma. The inferior phrenic artery is seen as an important source of collateral arterial supply to hepatocellular carcinoma, the hepatic artery being the main source. Materials and methods: A cadaveric study was conducted in the Anatomy Department of Bangalore Medical College during the years 2009–2011. Manual dissection was done to identify the inferior phrenic arteries, and their origins were traced. Results: The inferior phrenic artery arose from the aorta in 53.125%, celiac trunk in 28.125%, renal artery in 15.625%, and the superior mesenteric artery in 3.125% of the 32 cadavers studied. The right inferior phrenic artery arose from aorta in 56.25%, celiac trunk in 18.75%, renal artery in 18.75%, and superior mesenteric artery in 6.25% cases. The left inferior phrenic artery arose from aorta in 50%, from celiac trunk in 37.5%, and the rest arose (12.5%) from the renal artery. Discussion: The results were compared with those of earlier studies so that such findings could be applied in the treatment of hepatocellular carcinoma. The significance of this information is due to the fact that an unresectable hepatocellular carcinoma can be treated by transcatheter embolization of the right inferior phrenic artery, in case it is involved.     

Genotoxic stress accelerates age-associated degenerative changes in intervertebral discs

Intervertebral disc degeneration (IDD) is the leading cause of debilitating spinal disorders such as chronic lower back pain. Aging is the greatest risk factor for IDD. Previously, we demonstrated IDD in a murine model of a progeroid syndrome caused by reduced expression of a key DNA repair enzyme. This led us to hypothesize that DNA damage promotes IDD. To test our hypothesis, we chronically exposed adult wild-type (Wt) and DNA repair-deficient Ercc1^?/Δ mice to the cancer therapeutic agent mechlorethamine (MEC) or ionization radiation (IR) to induce DNA damage and measured the impact on disc structure. Proteoglycan, a major structural matrix constituent of the disc, was reduced 3–5× in the discs of MEC- and IR-exposed animals compared to untreated controls. Expression of the protease ADAMTS4 and aggrecan proteolytic fragments was significantly increased. Additionally, new PG synthesis was reduced 2–3× in MEC- and IR-treated discs compared to untreated controls. Both cellular senescence and apoptosis were increased in discs of treated animals. The effects were more severe in the DNA repair-deficient Ercc1^?/Δ mice than in Wt littermates. Local irradiation of the vertebra in Wt mice elicited a similar reduction in PG. These data demonstrate that genotoxic stress drives degenerative changes associated with IDD.     

The expression of heterochromatin protein 1α/β in the kidney tumors: a microarray immunohistochemical study

Kidney tumors of various types may behave differently and have different prognosis. Due to some overlapping morphological features and immunohistochemical staining pattern, they may pose diagnostic challenge. Therefore, it is necessary to explore additional immunohistochemical stains to help in subclassifying these epithelial neoplasms. Tissue microarrays of 20 cases each of renal cell carcinomas (RCC) of clear cell, chromophobe, and papillary variants and oncocytoma were constructed and used to test the heterochromatin-associated protein (HP) 1α/β expression. HP-1α/β showed strong nuclear staining. Expression of HP-1α/β was found mostly in papillary RCC (79%) and oncocytoma (75%) but less in chromophobe (30%) and clear cell RCCs (35%). HP-1α/β may be useful in the differential diagnosis of renal tumors, especially in the differentiation of chromophobe RCC and oncocytoma.     

Redefining the proximal ulna anatomy

Purpose

Complex fractures of the olecranon have always been a difficult condition for treatment. Successful reconstruction depends on restoration of the anatomic contributors to stability. The purpose of this study was to define the proximal ulna anatomy in detail with respect to fracture fixation and arthroscopy.

Methods

In 50 normal adult ulnae (26 left, 24 right); posterior olecranon height (POH), olecranon width (OW), trochlear notch width (TW), the distances between the olecranon and the trochlear notch on radial and ulnar sides (RTH, UTH), and proximal ulnar angulations were measured with a ruler and a digital goniometer.

Results

The average POH was 24.6 mm, OW was 23.1 mm, TW was 22.3 mm, RTH was 16.2 mm, and UTH was 15.8 mm. The mean value for proximal ulna torsion angle (PUTA) was found 11.1°. The mean varus angulation was 9.3°. The average articular angle was 27.7° and proximal ulnar dorsal angulation (PUDA) was 8°.

Conclusions

The unique bony architecture of the proximal ulna presents particular difficulties for the implants used in fracture fixation and arthroplasty of the elbow. Knowing the detailed anatomy of the variations of proximal ulna will guide the surgeon to obtain a more reliable length of the olecranon and to offer a safe place for Kirschner wire replacement concerning humero-ulnar joint functionality. In this study, PUTA was also defined. The angle determines the rotation of the proximal ulna and it has a great importance for the movements of the joint. The measured angulations will help the surgeon to design the proper prosthesis for the maintenance of the functions of the elbow joint.     

Gelatine methacrylamide-based hydrogels: An alternative three-dimensional cancer cell culture system

Modern cancer research requires physiological, three-dimensional (3-D) cell culture platforms, wherein the physical and chemical characteristics of the extracellular matrix (ECM) can be modified. In this study, gelatine methacrylamide (GelMA)-based hydrogels were characterized and established as in vitro and in vivo spheroid-based models for ovarian cancer, reflecting the advanced disease stage of patients, with accumulation of multicellular spheroids in the tumour fluid (ascites). Polymer concentration (2.5–7% w/v) strongly influenced hydrogel stiffness (0.5 ± 0.2 kPa to 9.0 ± 1.8 kPa) but had little effect on solute diffusion. The diffusion coefficient of 70 kDa fluorescein isothiocyanate (FITC)-labelled dextran in 7% GelMA-based hydrogels was only 2.3 times slower compared to water. Hydrogels of medium concentration (5% w/v GelMA) and stiffness (3.4 kPa) allowed spheroid formation and high proliferation and metabolic rates. The inhibition of matrix metalloproteinases and consequently ECM degradability reduced spheroid formation and proliferation rates. The incorporation of the ECM components laminin-411 and hyaluronic acid further stimulated spheroid growth within GelMA-based hydrogels. The feasibility of pre-cultured GelMA-based hydrogels as spheroid carriers within an ovarian cancer animal model was proven and led to tumour development and metastasis. These tumours were sensitive to treatment with the anti-cancer drug paclitaxel, but not the integrin antagonist ATN-161. While paclitaxel and its combination with ATN-161 resulted in a treatment response of 33–37.8%, ATN-161 alone had no effect on tumour growth and peritoneal spread. The semi-synthetic biomaterial GelMA combines relevant natural cues with tunable properties, providing an alternative, bioengineered 3-D cancer cell culture in in vitro and in vivo model systems.