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BackgroundHindfoot malalignment is a recognized cause of foot and ankle disability. For preoperative planning and clinical follow-up, reliable radiographic assessment of hindfoot alignment is important. The long axial radiographic view and the hindfoot alignment view are commonly used for this purpose. However, their comparative reliabilities are unknown. As hindfoot varus or valgus malalignment is most pronounced during mid-stance of gait, a unilateral weight-bearing stance, in comparison with a bilateral stance, could increase measurement reliability. The purpose of this study was to compare the intra- and interobserver reliability of hindfoot alignment measurements of both radiographic views in bilateral and unilateral stance.Materials and methodsA hindfoot alignment view and a long axial view were acquired from 18 healthy volunteers in bilateral and unilateral weight-bearing stances. Hindfoot alignment was defined as the angular deviation between the tibial anatomical axis and the calcaneus longitudinal axis from the radiographs. Repeat measurements of hindfoot alignment were performed by nine orthopaedic examiners.ResultsMeasurements from the hindfoot alignment view gave intra- and interclass correlation coefficients (CCs) of 0.72 and 0.58, respectively, for bilateral stance and 0.91 and 0.49, respectively, for unilateral stance. The long axial view showed, respectively, intra- and interclass CCs of 0.93 and 0.79 for bilateral stance and 0.91 and 0.58 for unilateral stance.ConclusionThe long axial view is more reliable than the hindfoot alignment view or the angular measurement of hindfoot alignment. Although intra-observer reliability is good/excellent for both methods, only the long axial view leads to good interobserver reliability. A unilateral weight-bearing stance does not lead to greater reliability of measurement.

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Diagnostic study, Level I.

We present a 3-portal approach for arthroscopic subtalar arthrodesis with the patient in the prone position. The prone position allows the use of the two standard posterior portals and it allows for accurate control of hindfoot alignment during surgery. Furthermore, the introduction of talocalcaneal lag screws is easy with the patient in this position. In addition to the standard posterior portals, an accessory third portal is created at the level of the sinus tarsi for introduction of a large diameter blunt trocar to open up the subtalar joint. Due to the curved geometry of the posterior subtalar joint, removal of the anterior articular cartilage is impossible by means of the posterior portals only. An advantage of the 3-portal approach is that ring curettes can be introduced through the accessory sinus tarsi portal to remove the articular cartilage of the anterior part of the posterior talocalcaneal joint. Arthroscopic subtalar arthrodesis in patients with a talocalcaneal coalition presents a technical challenge as the subtalar joint space is limited. The 3-portal technique was successfully used in three subsequent patients with a talocalcaneal coalition; bony union of the subtalar arthrodesis occurred at 6 weeks following surgery. With the 3-portal technique, a safe and time-efficient arthroscopic subtalar arthrodesis can be performed even in cases with limited subtalar joint space such as in symptomatic talocalcaneal coalition.

CRIPTO (CR-1, TDGF1) is a cell surface/secreted oncoprotein actively involved in development and cancer. Here, we report that high expression of CRIPTO correlates with poor survival in stratified risk groups of prostate cancer (PCa) patients. CRIPTO and its signaling partner glucose-regulated protein 78 (GRP78) are highly expressed in PCa metastases and display higher levels in the metastatic ALDHhigh sub-population of PC-3M-Pro4Luc2 PCa cells compared with non-metastatic ALDHlow. Coculture of the osteotropic PC-3M-Pro4Luc2 PCa cells with differentiated primary human osteoblasts induced CRIPTO and GRP78 expression in cancer cells and increases the size of the ALDHhigh sub-population. Additionally, CRIPTO or GRP78 knockdown decreases proliferation, migration, clonogenicity and the size of the metastasis-initiating ALDHhigh sub-population. CRIPTO knockdown reduces the invasion of PC-3M-Pro4Luc2 cells in zebrafish and inhibits bone metastasis in a preclinical mouse model. These results highlight a functional role for CRIPTO and GRP78 in PCa metastasis and suggest that targeting CRIPTO/GRP78 signaling may have significant therapeutic potential.

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Urological malignancies, including prostate and bladder carcinoma, represent a major clinical problem due to the frequent occurrence of therapy resistance and the formation of incurable distant metastases. As a result, there is an urgent need for versatile and predictive disease models for the assessment of the individualized drug response in urological malignancies. Compound testing on ex vivo cultured patient-derived tumor tissues could represent a promising approach. In this study, we have optimized an ex vivo culture system of explanted human prostate and bladder tumors derived from clinical specimens and human cancer cell lines xenografted in mice. The explanted and cultured tumor slices remained viable and tissue architecture could be maintained for up to 10 days of culture. Treatment of ex vivo cultured human prostate and bladder cancer tissues with docetaxel and gemcitabine, respectively, resulted in a dose-dependent anti-tumor response. The dose-dependent decrease in tumor cells upon administration of the chemotherapeutic agents was preceded by an induction of apoptosis. The implementation and optimization of the tissue slice technology may facilitate the assessment of anti-tumor efficacies of existing and candidate pharmacological agents in the complex multicellular neoplastic tissues from prostate and bladder cancer patients. Our model represents a versatile “near-patient” tool to determine tumor-targeted and/or stroma-mediated anti-neoplastic responses, thus contributing to the field of personalized therapeutics.