Imaging in prostate cancer.

Prostate cancer is the most common malignancy in men, in general. Most patients diagnosed with prostate cancer have localized disease confined to the prostate. A small percentage of patients with aggressive tumors will progress to develop local, extracapsular tumor extension and distant metastases. The aim of prostate cancer management is to identify and treat those patients with aggressive disease before they develop locally advanced or metastatic disease, and to avoid overtreating indolent tumors, which are unlikely to be life threatening. Imaging has been shown to be valuable in local staging of prostate cancer and as an aid to the management of clinically significant disease. In this article, we discuss the different established imaging modalities and emerging techniques for prostate cancer imaging in patients with clinically localized disease who may be suitable for radical treatment.

A preliminary examination of the role of NFAT 3 in human skin, cultured keratocytes and dermal fibroblasts.

BACKGROUND: Ciclosporin A (CsA) is widely utilized for the treatment of inflammatory skin diseases such as psoriasis.The therapeutic effects of CsA are thought to be mediated via its immunosuppressive action on infiltrating lymphocytes in skin lesions. CsA and tacrolimus block T cell activation by inhibiting the phosphatase calcineurin and preventing translocation from the cytoplasm to the nucleus of the transcription factor Nuclear Factor of Activated T cells (NFAT). METHODS: RT-PCR and Western Analysis were used to investigate the presence of NFAT-3 mRNA and protein in human keratocytes. Tissue culture of human keratocytes and immunostaining of cells on coverslips and confocal microscopy were used to assess the degree of nuclear localisation of NFAT-3 in cultured cells. Keratome biopsies were taken from patients with psoriasis (lesional and non-lesional skin) and normal skin and immunohistochemistry was used to assess the NFAT-3 localisation in these biopsies using a well characterized anti-NFAT-3 antibody. RESULTS: The NFAT-3 mRNA and protein expression was demonstrated using RT-PCR and Western blotting. The expression of NFAT-3 in human keratocytes and response to different agonists provides perhaps a unique opportunity to examine the regulation, subcellular localization and kinetics of translocation of different NFATs in primary cultured human cells. As with NFAT 1, NFAT 2 and recently NFAT 5, differentiation-promoting agents that increase intracellular calcium concentration induced nuclear translocation of NFAT-3 in cultured keratocytes but with different kinetics. CONCLUSION: These data provide the first evidence of that NFAT-3 is expressed in normal skin, psoriasis and that NFAT-3 functionally active in human keratocytes and that nuclear translocation of NFAT-3 in human skin cells has different kinetics than NFAT 1 suggesting that NFAT-3 may play an important role in regulation of keratocytes proliferation and differentiation at a different stage. Inhibition of this pathway in human epidermal keratocytes many account, in part for the therapeutic effects of CsA and tacrolimus in skin disorders such as psoriasis.

Transhepatic assisted transoral placement of a duodenal stent in malignant gastric outlet obstruction.

Gastric outlet obstruction is a well- recognized complication of locally advanced carcinoma of the head of the pancreas. The authors report a transoral placement of a duodenal stent over a percutaneous guide wire, inserted retrogradely through a transhepatic approach via the ampulla of Vater, in a patient in whom traditional stent placement was technically not possible. This technique allows safe duodenal stent placement for different malignant gastric outlet obstruction such as pancreatic, gastric, duodenal, and metastases to the peripancreatic region.

Modulation of NFAT-5, an outlying member of the NFAT family, in human keratinocytes and skin.

BACKGROUND: Cyclosporin A (CsA) and tacrolimus block T cell activation by inhibiting the phosphatase calcineurin and preventing translocation from the cytoplasm to the nucleus of the transcription factor Nuclear Factor of Activated T cells (NFAT). NFAT compose a family of transcription factors that are turned on during T cell activation. AIMS: To study the expression of NFAT-5 mRNA and protein in normal human keratinocytes and to investigate the cellular and subcellular pattern of expression of NFAT-5 in normal human skin and psoriasis, and analyze effects of different agonists and ultraviolet radiation on NFAT-5 in normal human skin. METHODS: Tissue cultures, Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR), Western analysis, immunostaining, confocal microscopy. RESULTS: Sequencing of RT-PCR products confirmed the identity of the product that showed 100 % homology with the predicted NFAT-5 sequence. anti-NFAT-5 mainly detected a single band in cultured keratinocytes and dermal fibroblasts using Western analysis. Immunohistochemistry showed that epidermal keratinocytes and dermal fibroblasts in normal human and psoriatic skin express NFAT-5. NFAT-5 showed predominantly nuclear localization in epidermal keratinocytes and dermal fibroblasts within five normal adult skin biopsies. Our data also suggest that UV irradiation reduces NFAT-5 nuclear localization within the epidermis. Unlike NFAT 1-4, NFAT-5/TonEBP was localized to both nucleus and cytoplasm of cultured keratinocytes. Cyclosporin A induces nuclear membrane translocation of NFAT-5 in cultured keratinocytes and raffinose (a hypertonicity inducing agent) induces more nuclear localization of NFAT-5 compared to untreated cells. In addition, differentiation-promoting agonists that induce sustained rise in intracellular calcium did not result in changes in NFAT-5 localization in cultured keratinocytes. CONCLUSION: These studies provide the first observation of expression of NFAT-5/TonEBP mRNA protein in cultured keratinocytes and dermal fibroblasts and possible functional regulation in cultured keratinocytes. CsA and raffinose effects on NFAT-5/TonEBP in cultured keratinocytes suggest diverse intracellular signaling pathways for NFAT-5/TonEBP in these cells, and that NFAT-5/TonEBP might function to translate different extracellular stimuli into appropriate functional responses.

Expression, localisation and functional activation of NFAT-2 in normal human skin, psoriasis, and cultured keratocytes.

Ciclosporin A (CsA) is widely utilized for the treatment of inflammatory skin diseases such as psoriasis. The therapeutic effects of CsA are thought to be mediated via its immunosuppressive action on infiltrating lymphocytes in skin lesions. CsA and tacrolimus block T cell activation by inhibiting the phosphatase calcineurin and preventing translocation from the cytoplasm to the nucleus of the transcription factor Nuclear Factor of Activated T cells (NFAT). As calcineurin and NFAT 1 have been shown to be functionally active in cultured human keratocytes, expression of other NFAT family members such as NFAT-2 and possible functional activation was investigated in human keratocytes. RT-PCR and Western Analysis were used to investigate the presence of NFAT-2 mRNA and protein in human keratocytes. Tissue culture of human keratocytes and immunostaining of cells on coverslips and confocal microscopy were used to assess the degree of nuclear localisation of NFAT-2 in cultured cells. Keratome biopsies were taken from patients with psoriasis (lesional and non-lesional skin) and normal skin and immunohistochemistry was used to assess the NFAT-2 localisation in these biopsies using a well characterized anti-NFAT-2 antibody. The NFAT-2 mRNA and protein expression was demonstrated using RT-PCR and Western blotting. Moreover, the expression of NFAT-2 in normal skin, non-lesional and lesional psoriasis showed a striking basal staining suggesting a role for NFAT-2 in keratocytes proliferation. A range of cell types in the skin express NFAT-2. The expression of NFAT-2 in human keratocytes and response to different agonists provides perhaps a unique opportunity to examine the regulation, subcellular localization and kinetics of translocation of different NFATs in primary cultured human cells. In these experiments the author assessed the expression, localization of NFAT-2 in cultured human keratocytes and measured the degree of nuclear localisaion of NFAT-2 using immunofluorescence and confocal microscopy and whether CsA and tacrolimus inhibit NFAT-2 nuclear translocation. As with NFAT 1, differentiation-promoting agents that increase intracellular calcium concentration induced nuclear translocation of NFAT-2 in cultured keratocytes but with different kinetics. These data provide the first evidence of that NFAT-2 is expressed in normal skin, psoriasis and that NFAT-2 functionally active in human keratocytes and that nuclear translocation of NFAT-2 in human skin cells has different kinetics than NFAT 1 suggesting that NFAT-2 may play an important role in regulation of keratocytes proliferation and differentiation at a different stage. Inhibition of this pathway in human epidermal keratocytes many account, in part for the therapeutic effects of CsA and tacrolimus in skin disorders such as psoriasis. Thus, supporting our previous work data that calcineurin/NFAT is functionally active not only in T cells, but in skin cells.

Radiofrequency ablation of renal tumors.

Development of cross-sectional imaging has led to a significant increase in diagnosis of small renal tumors. Nephron-sparing surgery has proven to be effective in the management of these small tumors. Could radiofrequency ablation be as effective in the management of these patients, after showing promising results in a selected group of patients? In this article we discuss the principles of radiofrequency ablation and present results in a selected group of patients. We also outline future perspectives of this noninvasive technique.

Lower limb paralysis from ischaemic neuropathy of the lumbosacral plexus following aorto-iliac procedures.

OBJECTIVES: Neurological injuries following aorto-iliac procedures are rare, unpredictable and cause significant morbidity. We report four cases of lower limb paralysis following aorto-iliac procedures, in which two patients suffered internal iliac occlusion and discuss potential aetiological factors. METHODS: Four male patients, age ranging between 56 and 77 years, underwent aorto-iliac procedures. Three patients underwent repair of infra-renal abdominal aortic aneurysm (2 open and 1 endovascular repair) and one patient had percutaneous angioplasty of the internal iliac artery. RESULTS: All patients developed a unilateral lower limb paralysis early post procedure. Neurophysiological studies were performed in three patients and confirmed the injury to the lumbosacral plexus in two cases. MRI scan performed in two patients did not show any abnormality. In two of the cases, occlusion of one internal iliac artery was implicated as the cause of lumbo-sacral plexopathy: one with the coverage of the internal artery origin with the stent, the other due to thrombotic occlusion of common and internal iliac in arteries after an elective open repair of abdominal aortic aneurysm with a bifurcated graft. Follow up ranged between 2 and 4 months. Only one patient recovered completely; the other three were left with permanent disability. CONCLUSIONS: Ischaemic neuropathy following aorto-iliac intervention, whether open or endovascular, remains a rare, unpredictable and devastating complication. When it occurs it is likely to result in permanent neurological disability. It is important to note that it may be related to internal iliac artery thrombosis.

Endoscopic assisted transaxillary first rib resection.

OBJECTIVES: Endoscopic assisted transaxillary first rib resection is a novel approach in the management of thoracic outlet syndrome. It allows safe identification of the different structures. The objective of our study is to assess the outcome of surgical treatment of thoracic outlet syndrome using this technique. METHODS: Between May 1999 and October 2005, 28 endoscopic assisted transaxillary first rib resections were performed on 20 patients with thoracic outlet syndrome in our vascular unit. This retrospective study included 14 females and 6 males with ages ranging between 16 and 53 years (median 37 years). RESULTS: Prior to the operation, all patients had C spine X-ray and 45% (nine patients) had nerve conduction studies prior to the operation. Duration of symptoms ranged between 1 month and 15 years (median 36 months). Fifty-five percent of patients had neurological symptoms, 30% had mixed symptoms and only 15% had venous or arterial symptoms. Eight patients were given bilateral first rib excision. The average time between the two operations was 17.5 months (median 12 months). The postoperative stay in hospital ranged between 2 and 8 days (median 5 days). Follow-up ranged between 1 and 64 months (median 8 months). Eighty-two percent of patients (23 resections) had complete resolution of symptoms. Eighteen percent (5 resections) did not show any improvement of symptoms following surgery. Three complications were recorded, including haemothorax, bleeding and brachial plexus injury. The latter was due to traction injury during the operation. CONCLUSIONS: Endoscopic assisted transaxillary first rib resection is a safe and effective procedure in the management of thoracic outlet syndrome. It also offers a great opportunity for teaching.