Medically treated prolactin-secreting pituitary adenomas: when should we operate?

BACKGROUND: The incidence of medical failure for prolactin (PRL)-secreting pituitary tumours is not well known. Object. The purpose of this study is to report clinical, radiographic and laboratory findings of PRL-secreting tumours that predict failed medical management. METHODS: An analysis of 92 consecutive patients was performed that met the inclusion criteria. Decision for surgery was made based on failure of dopamine agonists to either control clinical symptoms and normalise hormonal level or diminish mass effect on follow-up evaluation. RESULTS: Of the 92 patients treated, 14 patients (15%) required trans-nasal, trans-sphenoidal pituitary surgery (TSS). One patient underwent surgery for repair of a skull defect and 13 patients (14%) required surgery after failed medical management. Higher initial PRL was statistically significant regarding the need for surgical intervention, but a persistently abnormal level after initiation of treatment was a more significant predictor (Fisher exact test, p = 0.005 vs. p < 0.001). Size was also a statistically significant factor (p = 0.014); macroadenomas had a relative risk of 9.27 (95% CI: 1.15-74.86) for needing surgery compared to microadenomas. In addition, macroadenomas with cavernous sinus (CS) extension and pre-operative visual field deficit demonstrated a strong tendency for surgical intervention. CONCLUSION: Medical management remains the most effective treatment option for prolactinomas. A partial hormonal response to medical management seems to be the most significant predictive factor but adenomas > 20 mm, visual field deficit and invasion of the CS may help predict the need for surgery. We suggest a minimum trial period (at least 8 weeks) of medical treatment prior to the consideration of surgery.

The coupling of epidermal growth factor receptor down regulation by 1alpha,25-dihydroxyvitamin D3 to the hormone-induced cell cycle arrest at the G1-S checkpoint in ovarian cancer cells.

1alpha,25-dihydroxyvitamin D3, 1,25(OH)(2)D(3), regulates gene expression through the vitamin D receptor. The present studies identify the epidermal growth factor receptor, EGFR, as a target gene suppressed by 1,25(OH)(2)D(3) in human ovarian cancer cells. The suppression was detected at both mRNA and protein levels in vitamin D-sensitive human ovarian cancer cells. A novel vitamin D response element was identified in intron 1 of the EGFR genome, a known hotspot for its transcriptional regulation. Chromatin immunoprecipitations and reporter gene analyses showed that the intronic DNA element bound to vitamin D receptor and a co-repressor and was functional in mediating transcriptional suppression of EGFR promoter by 1,25(OH)(2)D(3) under stable transfection conditions. Consistent with the EGFR down regulation, 1,25(OH)(2)D(3) suppressed activation of the external signal regulated kinase by epidermal growth factors. Over expression of an active EGFR in vitamin D sensitive ovarian cancer cells caused resistance to 1,25(OH)(2)D(3)-induced growth suppression and diminished the hormonal regulation of cyclin D1, cyclin E, Skp2 and p27, a group of cell cycle regulators that mediate 1,25(OH)(2)D(3)-induced cell cycle arrest at G1-S checkpoint. Taken together, our studies demonstrate that 1,25(OH)(2)D(3) suppresses the response of human ovarian cancer cells to mitogenic growth factors and couple the suppression to the cell cycle arrest at G1-S checkpoint by the hormone.

Phalloplasty and penile implant surgery.

Impotence is often accompanied by loss of phallic length. To enhance penile prosthesis surgery, it is possible to perform simple adjuvant procedures that will increase perceived or true length. This article presents an overview of these techniques, which may be categorized as involving removal or fixation of tissue above or below the shaft of the penis; division of the suspensory ligament; and augmentation of the corpora cavernosa through stretch or grafting. We believe that the use of these techniques will become increasingly commonplace as patient satisfaction is reported.