Malignant Melanoma Treated with Topical Imiquimod: A Bespoke Treatment That Spared the Amputation.

Surgical excision represents the primary treatment for malignant melanoma. On occasion, however, surgery may not be possible, and a different approach is required. Imiquimod is a Toll-like receptor 7 agonist involved in the activation of the innate immune system. We report the case of a 77-year-old female with a large, invasive, malignant melanoma of the malleolar area. Due to the size of the lesion, its location, and the patient's general condition, neither surgery nor radiotherapy were indicated. We offered topical treatment with 5% imiquimod to be applied once/day continuously over a 3-month period, pausing only when intense inflammation on the area of application occurred. Complete clinical and histological resolution of the lesion were observed. This case adds further merit to the growing body of evidence that imiquimod can be used to successfully treat malignant melanoma in cases where no other options are suitable.

A reciprocal feedback between the PDZ binding kinase and androgen receptor drives prostate cancer.

Elucidation of mechanisms underlying the increased androgen receptor (AR) activity and subsequent development of aggressive prostate cancer (PrCa) is pivotal in developing new therapies. Using a systems biology approach, we interrogated the AR-regulated proteome and identified PDZ binding kinase (PBK) as a novel AR-regulated protein that regulates full-length AR and AR variants (ARVs) activity in PrCa. PBK overexpression in aggressive PrCa is associated with early biochemical relapse and poor clinical outcome. In addition to its carboxy terminus ligand-binding domain, PBK directly interacts with the amino terminus transactivation domain of the AR to stabilise it thereby leading to increased AR protein expression observed in PrCa. Transcriptome sequencing revealed that PBK is a mediator of global AR signalling with key roles in regulating tumour invasion and metastasis. PBK inhibition decreased growth of PrCa cell lines and clinical specimen cultured ex vivo. We uncovered a novel interplay between AR and PBK that results in increased AR and ARVs expression that executes AR-mediated growth and progression of PrCa, with implications for the development of PBK inhibitors for the treatment of aggressive PrCa.

Efficacy of an incident-reporting system in cellular pathology: a practical experience.

BACKGROUND AND AIMS: Incident reporting (IR) refers to systematic documentation of adverse incidents to facilitate their appropriate investigation and institution of corrective or remedial actions, and provide data to identify risk trends for recurrent problems. Minimisation of errors and reduction in process variation is recognised as an important goal of quality management and is an essential part of continuous quality improvement. Published data on the role IR plays in cellular pathology remains scanty. METHODS: In this study, the authors collected and analysed all incidents and adverse events reported in their department over a 2-year period. RESULTS: 584 incidents were reported (0.5% of all cases processed). The majority (59%) occurred in the pre-analytical phase of the laboratory process with 23% in the analytical and 18% in the post-analytical phases. Booking-in and specimen labelling-related incidents were the largest single group (56% of all incidents), prompting further root cause analysis, but no other obvious patterns or trends were identified, and most incidents were followed by corrective actions on an individual basis. Most incidents (79%) posed potential harm, as opposed to causing actual harm to the service or patients. Only 78 cases (14%) posed a major risk to patients, such as specimen loss or mix-up, whereas 27% were associated with moderate risk and 59% with minor or insignificant risk. CONCLUSION: Major risk incidents are relatively rare in the cellular pathology laboratory. IR should be included as an important component of a risk management strategy and clinical governance framework.