MRI of ovarian torsion: Correlation of imaging features with the presence of perifollicular hemorrhage and ovarian viability.

PURPOSE: The purpose of our study is to test for: (a) correlation between the presence of a perifollicular T2-hypointense rim on MRI with the presence of perifollicular hemorrhage on histology; and (b) correlation between this finding and diminished ovarian viability after intra-operative detorsion. METHODS AND MATERIALS: Our IRB-approved, retrospective study evaluated 780 patients between August 2012 and February 2016 with ovarian torsion as a diagnostic consideration on the emergency department note. Patients were included if they had preoperative MRI and intraoperatively confirmed case of ovarian torsion. MRIs were retrospectively reviewed for presence of perifollicular T2 hypointense rim in the torsed ovary. Two arms of analysis were performed: (a) assessment of perifollicular hemorrhage on histological exam; and (b) assessment of ovarian viability after intra-operative detorsion. Sensitivity, specificity, positive predictive value, and negative predictive value of MRI for predicting ovarian viability in the setting of torsion was performed. κ test assessed level of agreement between readers. RESULTS: 24 patients included in one of the two arms; 20 in viability analysis and 12 in perifollicular hemorrhage analysis (8 in both). The presence of T2-hypointense rim on MRI demonstrated 88.9% sensitivity and 66.7% specificity for the diagnosis of perifollicular hemorrhage on histology, and 91.7% sensitivity and 100% specificity for predicting intraoperative viability. CONCLUSION: The presence of a perifollicular T2 hypointense rim on MRI in the setting of ovarian torsion correlates with perifollicular hemorrhage on histopathologic exam, and may also be a useful predictor of ovarian viability in patients presenting with ovarian torsion.

Variants of human papillomavirus type 16 predispose toward persistent infection.

A cohort study of 292 Chinese women was conducted to determine the relationship between human papillomavirus (HPV) type 16 variants and persistent viral infection. Enrolled patients were HPV16 positive and had both normal cytology and histology. Flow-through hybridization and gene chip technology was used to identify the HPV type. A PCR sequencing assay was performed to find HPV16 E2, E6 and E7 gene variants. The associations between these variants and HPV16 persistent infection was analyzed by Fisher's exact test. It was found that the variants T178G, T350G and A442C in the E6 gene, as well as C3158A and G3248A variants in the E2 gene were associated with persistent HPV16 infection. No link was observed between E7 variants and persistent viral infection. Our findings suggest that detection of specific HPV variants would help identify patients who are at high risk for viral persistence and development of cervical neoplasia.

Combined micro CT and histopathology for evaluation of skeletal metastasis in live animals.

Bone is a favored site for solid tumor metastasis, especially among patients with breast, lung or prostate carcinomas. Micro CT is a powerful and inexpensive tool that can be used to investigate tumor progression in xenograft models of human disease. Many previous studies have relied on terminal analysis of harvested bones to document metastatic tumor activity. The current protocol uses live animals and combines sequential micro CT evaluation of lesion development with matched histopathology at the end of the study. The approach allows for both rapid detection and evaluation of bone lesion progression in live animals. Bone resident tumors are established either by direct (intraosseous) or arterial (intracardiac) injection, and lesion development is evaluated for up to eight weeks. This protocol provides a clinically relevant method for investigating bone metastasis progression and the development of osteotropic therapeutic strategies for the treatment of bone metastases.

Targeting integrin α6 stimulates curative-type bone metastasis lesions in a xenograft model.

Laminin-binding integrin receptors are key mediators of epithelial cell migration and tumor metastasis. Recent studies have demonstrated a role for the α6 integrin (ITGA6/CD49f) in maintaining stem cell compartments within normal bone marrow and in residency of tumors metastatic to bone. In this study, we tested a function-blocking antibody specific for ITGA6, called J8H, to determine if preexisting cancer lesions in bone could be slowed and/or animal survival improved. Human prostate tumors were established by intracardiac injection into male SCID mice and treatment with J8H antibody was initiated after 1 week. Tumor progression was monitored by micro-computed tomography (CT) imaging of skeletal lesions. Animals that received weekly injections of the anti-ITGA6 antibody showed radiographic progression in only 40% of osseous tumors (femur or tibia), compared with control animals, where 80% of the lesions (femur or tibia) showed progression at 5 weeks. Kaplan-Meier survival analysis demonstrated a significant survival advantage for J8H-treated animals. Unexpectedly, CT image analysis revealed an increased proportion of bone lesions displaying a sclerotic rim of new bone formation, encapsulating the arrested lytic lesions in animals that received the anti-ITGA6 antibody treatment. Histopathology of the sclerotic lesions demonstrated well-circumscribed tumor within bone, surrounded by fibrosis. These data suggest that systemic targeting of the ITGA6-dependent function of established tumors in bone may offer a noncytotoxic approach to arrest the osteolytic progression of metastatic prostate cancer, thereby providing a new therapeutic strategy for advanced disease.

In vivo telemetric determination of shear and axial loads on a regenerative cartilage scaffold following ligament disruption.

Recent interest in repair of chondral and osteochondral cartilage defects to prevent osteoarthritis caused by ligament disruption has led to the research and development of biomimetic scaffolds combined with cell-based regeneration techniques. Current clinical focal defect repair strategies have had limited success. New scaffold-based approaches may provide solutions that can repair extensive damage and prevent osteoarthritis. This study utilized a novel scaffold design that accommodated strain gauges for shear and axial load monitoring in the canine stifle joint through implantable telemetry technology. Loading changes induced by ligament disruption are widely implicated in the development of injury-related osteoarthritis. Seeding the scaffold end with progenitor cells resulted in higher shear stress than without cell seeding and histology showed significantly more bone and cartilage formation. Biomechanically, the effect of transecting the anterior cruciate ligament was a significant reduction in braking load in shear, but no change axially, and conversely a significant reduction in push-off load axially, but no change in shear. This is the first study to report shear loads measured directly in knee joint tissue. Further, advances of these measurement techniques are critical to developing improved regeneration strategies and personalizing reliable rehabilitation protocols.

Biomechanical evaluation of suture-augmented locking plate fixation for proximal third fractures of the olecranon.

OBJECTIVES: To describe a method of suture augmentation of locking plate fixation (PF) of proximal olecranon fractures and to evaluate the biomechanical effectiveness of the suture augmentation using a human cadaveric model. METHODS: Six matched pairs of cadaveric elbows were used. Proximal one-third fractures of the olecranon were simulated via a transverse osteotomy. Identical locking PF was performed on each elbow using olecranon locking plates. One elbow of each pair was assigned to suture augmentation of the construct. The choice of left/right specimen for augmentation was performed in an alternating fashion. Augmentation was performed using a no. 2 ultra-high-molecular weight polyethylene-braided suture attaching the triceps to the plate via a modified Krackow stitch. The elbows were mounted into a custom jig and linearly loaded to failure using a hydraulic testing machine. Load to and modes of failure were recorded for each sample. The data were analyzed using the Wilcoxon signed-rank test for nonparametric distributions. RESULTS: Suture augmentation improved the single load-to-failure strength in all pairs. One pair was excluded due to failure of the triceps attachment to the test machine. A median 398 N (P = 0.04 range, 197-633 N) or a median 48% (range, 30%-130%) improvement in strength was seen. The most common mode of failure was loss of fixation of the proximal olecranon fragment. CONCLUSIONS: Suture augmentation can significantly increase the single load-to-failure strength of locking PF for proximal olecranon fractures.

Bone cancer pain.

In the United States, cancer is the second most common cause of death and it is expected that about 562,340 Americans will have died of cancer in 2009. Bone cancer pain is common in patients with advanced breast, prostate, and lung cancer as these tumors have a remarkable affinity to metastasize to bone. Once tumors metastasize to bone, they are a major cause of morbidity and mortality as the tumor induces significant skeletal remodeling, fractures, pain, and anemia. Currently, the factors that drive cancer pain are poorly understood. However, several recently introduced models of bone cancer pain, which closely mirror the human condition, are providing insight into the mechanisms that drive bone cancer pain and guide the development of mechanism-based therapies to treat the cancer pain. Several of these mechanism-based therapies have now entered human clinical trials. If successful, these therapies have the potential to significantly enlarge the repertoire of modalities that can be used to treat bone cancer pain and improve the quality of life, functional status, and survival of patients with bone cancer.