Capturing complex tumour biology in vitro: histological and molecular characterisation of precision cut slices.

Precision-cut slices of in vivo tumours permit interrogation in vitro of heterogeneous cells from solid tumours together with their native microenvironment. They offer a low throughput but high content in vitro experimental platform. Using mouse models as surrogates for three common human solid tumours, we describe a standardised workflow for systematic comparison of tumour slice cultivation methods and a tissue microarray-based method to archive them. Cultivated slices were compared to their in vivo source tissue using immunohistochemical and transcriptional biomarkers, particularly of cellular stress. Mechanical slicing induced minimal stress. Cultivation of tumour slices required organotypic support materials and atmospheric oxygen for maintenance of integrity and was associated with significant temporal and loco-regional changes in protein expression, for example HIF-1α. We recommend adherence to the robust workflow described, with recognition of temporal-spatial changes in protein expression before interrogation of tumour slices by pharmacological or other means.

Tumour stromal morphology impacts nanomedicine cytotoxicity in patient-derived xenografts.

It is challenging to evaluate how tumour pathophysiology influences nanomedicine therapeutic effect; however, this is a key question in drug delivery. An advanced analytical method was developed to quantify the spatial distribution of drug-induced effect in tumours with varied stromal morphologies. The analysis utilises standard immunohistochemistry images and quantifies the frequency of positive staining as a function of distance from the stroma. Two stromal morphologies - Estuary and Tumour Island - were classified in 28 tumours from a lung cancer explant model in mice treated with liposomal doxorubicin. Analysis demonstrated that Estuary-like tumours presented a highly convoluted tumour-stroma interface, with most tumour cells in close proximity to vessels; these tumours were 8.8-fold more responsive to liposomal doxorubicin than were Tumour Island-like tumours, which were nearly unresponsive to liposomal doxorubicin. SDARS analysis allows the relative treatment effect to be assessed in tumours individually, and enables investigation of nanomedicine delivery in complex tumour pathophysiologies. FROM THE CLINICAL EDITOR: Advances in nanotechnology have brought about many novel treatment modalities for cancer. Nonetheless, there is no standard evaluation technique for tumor cells' drug response. The authors here utilized patient-derived tumour xenograft (PDTX) models to have a more translatable pre-clinical evaluation platform for nanomedicine drugs. They then used advanced imaging acquisition technique to analyze tumor stromal morphology, which they named Spatial Distribution of Apoptosis Relative to Stroma (SDARS). The findings would have significant clinical impact as it would help predict the eventual clinical drug response.

Assessment of quality of life after surgery for spinal metastases: position statement of the Global Spine Tumour Study Group.

OBJECTIVE: To review suitable measures of patient-assessed outcome of surgery for spinal metastases, and suggest the Health-Related Quality of Life measures that are useful and practical for this group of patients. METHODS: Surgery for metastatic spinal tumors is becoming more common, but the impact of surgery on the patient, as determined by patient-assessed outcome measures, is not well known. The authors of this article include members of the Global Spine Tumour Study Group: an international group of spinal surgeons who are studying the techniques and outcomes of surgery for spinal tumors. During the development of a research database for the study of patients undergoing surgery for spinal metastases, the different outcome measures were discussed by a panel of spinal surgeons, and quality of life measures were chosen for inclusion, based on expert opinion and literature review. RESULTS: Several different measures are available to assess outcome after spinal surgery for metastatic disease, each with specific advantages and limitations, which are discussed. Our position is to use the EuroQoL EQ-5D questionnaire, because of its simplicity and reliability. CONCLUSIONS: We recommend the use of the EQ-5D measure in research for assessment of patient-centered outcomes and calculation of cost effectiveness of surgery for spinal metastases. Routine use of the measure in clinical practice is also encouraged, because it is a simple and quick method to assess overall clinical outcome.

Initial experience with EUS-guided cholangiopancreatography for biliary and pancreatic duct drainage: a Spanish national survey.

BACKGROUND: EUS-guided cholangiopancreatography (ESCP) allows transmural access to biliopancreatic ducts when ERCP fails. Data regarding technical details, safety, and outcomes of ESCP are still unknown. OBJECTIVE: To evaluate outcomes of ESCP in community and referral centers at the initial development phase of this procedure, to identify the ESCP stages with higher risk of failure, and to evaluate the influence on outcomes of factors related to the endoscopist. DESIGN: Multicenter retrospective study. SETTING: Public health system hospitals with experience in ESCP in Spain. PATIENTS: A total of 125 patients underwent ESCP in 19 hospitals, with an experience of <20 procedures. INTERVENTION: ESCP. MAIN OUTCOME MEASUREMENTS: Technical success and complication rates in the initial phase of implantation of ESCP are described. The influence of technical characteristics and endoscopist features on outcomes was analyzed. RESULTS: A total of 125 patients from 19 hospitals were included. Biliary ESCP was performed in 106 patients and pancreatic ESCP was performed in 19. Technical success was achieved in 84 patients (67.2%) followed by clinical success in 79 (63.2%). Complications occurred in 29 patients (23.2%). Unsuccessful manipulation of the guidewire was responsible for 68.2% of technical failures, and 58.6% of complications were related to problems with the transmural fistula. LIMITATIONS: Retrospective study. CONCLUSION: Outcomes of ESCP during its implantation stage reached a technical success rate of 67.2%, with a complication rate of 23.2%. Intraductal manipulation of the guidewire seems to be the most difficult stage of the procedure.

[Cutaneous metastases from transitional cell carcinoma of the bladder producing beta-HCG]. / Metástasis cutáneas de un carcinoma transicional vesical productor de beta-HCG.

In spite of the high incidence of transitional cell carcinoma, cutaneous metastases are infrequent, especially when they are the first sign of metastatic spread, with a low survival rate. Thirty five per cent of transitional cell carcinoma of the bladder have ectopic beta- human chorionic gonadotropin (beta-HCG) production. It has been related with high grade tumors, advanced stage, metastatic disease, radioresistent tumors and low survival rate because of its effect as a growth modulator with a probably antagonist action in the apoptotic cascade. We present a thirty six years old woman affected by a transitional cell carcinoma of the bladder producing beta-HCG that showed two cutaneous metastases as first sign of metastatic disease. The exceptional coincidence of these two circumstances announced a very aggressive tumor behaviour and bad prognostic, with a quickly multiple metastatic dissemination including a pericardic metastases.