Orbital exenteration for advanced periorbital non-melanoma skin cancer: prognostic factors and survival.

PurposeTo describe prognostic factors and survival outcomes in patients who underwent orbital exenteration for periocular non-melanoma cutaneous malignancies.MethodsThe authors performed an institutional review board-approved retrospective review of all patients who underwent orbital exenteration for non-melanoma periocular cutaneous malignancies at a tertiary care hospital system over a 10-year period. Patient demographics, tumor, and treatment data were recorded. Survival outcomes included disease-free survival (DFS) and overall survival (OS). Log-rank tests were used to test for difference in survival curves among various potential prognostic indicators, and multivariate analysis was performed using Cox's proportional hazards model.ResultsForty-nine patients with an average age of 70.3 years were followed with a median follow-up of 17.5 months. At 2 years the OS was 78% while the DFS was 61%. The mean DFS for basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and sebaceous gland carcinoma (SGC) were 52.6, 39.2 and 28.1 months, respectively. Multivariate analysis demonstrated that only positive final surgical margin was predictive of worse outcome (P=0.002). Recurrences were most frequent in the first 2 years.ConclusionsDespite the relatively more aggressive nature of periocular malignancies that have invaded the orbit, orbital exenteration offers an overall 2-year DFS of ~60%. BCC had the greatest mean survival time, however this was not statistically significant. We found worse prognosis with positive final surgical margins and recommend a multidisciplinary surgical approach to achieve complete resection when indicated.

A novel association of neuropilin-1 and MUC1 in pancreatic ductal adenocarcinoma: role in induction of VEGF signaling and angiogenesis.

We report that Mucin1 (MUC1), a transmembrane glycoprotein that is overexpressed in >80% of pancreatic ductal adenocarcinoma (PDA), induced a pro-angiogenic tumor microenvironment by increasing the levels of neuropilin-1 (NRP1, a co-receptor of vascular endothelial growth factor (VEGF)) and its ligand VEGF. Expression of tumor-associated MUC1 (tMUC1) positively correlated with NRP1 levels in human and mouse PDA. Further, tMUC1hi PDA cells secreted high levels of VEGF and expressed high levels of VEGF receptor 2 (VEGFR2) and its phosphorylated forms as compared with tMUC1low/null PDA. This enabled the tMUC1hi/NRP1hi PDA cells to (a) induce endothelial cell tube formation, (b) generate long ectopic blood vessels and (c) enhance distant metastasis in a zebrafish xenograft model. Concurrently, the proteins associated with epithelial-to-mesenchymal transition, N-cadherin and Vimentin, were highly induced in these tMUC1/NRP1hi PDA cells. Hence, blocking signaling via the NRP1-VEGF axis significantly reduced tube formation, new vessel generation and metastasis induced by tMUC1hi PDA cells. Finally, we show that blocking the interaction between VEGF165 and NRP1 with a NRP1 antagonist significantly reduced VEGFR signaling and PDA tumor growth in vivo. Taken together, our data suggest a novel molecular mechanism by which tMUC1 may modulate NRP1-dependent VEGFR signaling in PDA cells.

Improving the cancer patient journey.

The research discussed focuses on improving the delivery of cancer services, specifically lymphoma, at a regional Australian hospital. The work examines whether an emerging patient journey modeling technique known as Essomenic, which has been successfully applied in the domains of; midwifery, chronic kidney disease, mental health, ambulatory care, bariatric and osteoarthritis can deliver similar results to the highly time critical domain of cancer diagnosis and treatment commencement. The work also analysed if enhancements were required to the modelling syntax to accommodate domain specific requirements.

MUC1 regulates PDGFA expression during pancreatic cancer progression.

Pancreatic ductal adenocarcinoma (PDA) has one of the worst prognoses of all cancers. Mucin 1 (MUC1), a transmembrane mucin glycoprotein, is a key modulator of several signaling pathways that affect oncogenesis, motility and metastasis. Its expression is known to be associated with poor prognosis in patients. However, the precise mechanism remains elusive. We report a novel association of MUC1 with platelet-derived growth factor-A (PDGFA). PDGFA is one of the many drivers of tumor growth, angiogenesis and metastasis in PDA. Using mouse PDA models as well as human samples, we show clear evidence that MUC1 regulates the expression and secretion of PDGFA. This, in turn, influences proliferation and invasion of pancreatic cancer cells leading to higher tumor burden in vivo. In addition, we reveal that MUC1 overexpressing cells are heavily dependent on PDGFA both for proliferation and invasion, whereas MUC1-null cells are not. Moreover, PDGFA and MUC1 are critical for translocation of ß catenin to the nucleus for oncogenesis to ensue. Finally, we elucidate the underlying mechanism by which MUC1 regulates PDGFA expression and secretion in pancreatic cancer cells. We show that MUC1 associates with Hif1-α, a known transcription factor involved in controlling PDGFA expression. Furthermore, MUC1 facilitates Hif1-α translocation to the nucleus. In summary, we have demonstrated that MUC1-induced invasion and proliferation occurs via increased exogenous production of PDGFA. Thus, impeding MUC1 regulation of PDGFA signaling may be therapeutically beneficial for patients with PDA.

Patient journey modelling: using students as a vehicle for the diffusion of innovation.

This paper describes a case study involving third-year undergraduate computing students and their conduct of a patient journey modeling project for the Ambulatory Care department of a Regional Hospital in New South Wales, Australia. The goal of the research was to determine if students, given minimal training in an emerging patient journey modeling tool known as Essomenic, could be an effective vehicle for the diffusion of innovation to operational staff involved in a healthcare improvement project. Under academic supervision, students interacted directly with staff to develop models of the current system of care from GP referral to the completion of the patient consultation. The methodology also included model validation, identification of opportunities for improvement, investigation of alternative solutions and solution recommendations. Outcomes of the project, conducted over a 14 week semester, demonstrate that the students found the technique quick and easy to learn and that they could transfer their new found knowledge of this innovation to healthcare staff for the purposes of developing true and accurate representations of the current state patient journey. Staff were then able to interact directly with the student team, using the models as a communication medium, to identify opportunities for improvement and understand more deeply, how changes would impact their daily tasks and increase patient satisfaction in service delivery.

Acute renal failure secondary to ciprofloxacin use.

We report on a 22-year-old woman with a continent urinary diversion in whom acute renal failure developed on ciprofloxacin therapy for pelvic osteomyelitis. Renal failure resolved rapidly once the drug was withheld. Because ciprofloxacin is used extensively by the urological community, we believe that it is important to be aware of this potential complication of therapy. We review the literature on the association of ciprofloxacin and renal failure.

Congenital genitourinary hemangiomas in a patient with the Klippel-Trenaunay syndrome: management with the neodymium:YAG laser.

The Klippel-Trenaunay syndrome is an unusual congenital anomaly characterized by cutaneous hemangiomas, multiple varicosities, soft tissue hypertrophy and, rarely, gastrointestinal or genitourinary hemangiomas. The large bladder as well as multiple penile hemangiomas in our patient were treated successfully with the neodymium:YAG laser with minimal morbidity.