Laparoscopic partial nephrectomy without ischemia.

The warm ischaemia time appears the most prominent modifiable risk factor for the development of renal impairment following laparoscopic partial nephrectomy. Historically, hilar clamping was the 'gold standard' technique, but now we are pushing our techniques to achieve the ultimate: 'zero ischaemia' approach. Results from 'early unclamping' techniques reinforced the importance of 'every minute counts' (28). Subsequent techniques in non-hilar clamping demonstrated that this approach was indeed feasible, but at the expense of higher bleeding, positive margins, and collecting system breach rates. With the advancement of technology, through the use of robotic assistance, improved haemostatic agents, as well as various imaging modalities (laparoscopic ultrasound, CT angiography), the surgeon can now potentially perform Nephron Sparing Surgery (NSS) in a more precise manner. Specifically, with the use of superselective clamping of the feeding vessel(s) to the tumour, the remaining healthy renal parenchyma should be less compromised, with associated low bleeding rates. NSS in the form of laparoscopic partial nephrectomy is clearly evolving, with increasing demands on the surgeon, requiring more expertise and experience, with the added assistance from other specialties (anaesthetists, radiologists etc). To be able to regularly perform Laparoscopic Partial Nephrectomy (LPN) without ischaemia safely, the laparoscopist must develop his / her experience in a stepwise fashion, perhaps commencing with artery-only clamping, leading on to early declamping, and then 'on demand' clamping. When moving on to LPN without ischaemia, patient selection is paramount. The ideal patient would harbour a single small, polar, exophytic renal mass with a normal functioning contralateral kidney. Although currently the techniques and outcomes laparoscopic partial nephrectomy without ischaemia published are limited to a few authors, with no current long term results to prove its full worth and reproducibility, early results are very encouraging. The pursuit of acquiring 'zero ischaemia' is clearly worthwhile, but needs to be measured against the potential risks of increased morbidity and positive margin rates.

Nefrectomía parcial laparoscópica sin isquemia / Laparoscopic partial nephrectomy without ischaemia

El tiempo de isquemia caliente parece ser el factor de riesgo modificable más importante para el desarrollo de un deterioro de la función renal después de la nefrectomía parcial laparoscópica. Históricamente el clampaje del hilio era la técnica estándar de referencia, pero ahora estamos impulsando nuestras técnicas para conseguir lo último: el abordaje con isquemia cero. Los resultados de las técnicas de desclampaje precoz han reforzado la importancia del “cada minuto cuenta” (28). Las técnicas posteriores sin clampaje del hilio demostraron que este abordaje era de hecho factible, pero a expensas de un mayor sangrado, márgenes positivos y tasas de apertura del sistema colector. Con el avance de la tecnología, por medio de la utilización de asistencia robótica, mejores agentes hemostáticos, así cómo varias modalidades de imagen (Ecografía laparoscópica, TAC angiografía) el cirujano puede ahora potencialmente realizar cirugía conservadora de una forma más precisa. Específicamente, con el uso de clampaje súper selectivo del (de los) vaso(s) nutricio(s) del tumor el resto de parénquima sano debería comprometerse menos, con bajas tasas de sangrado asociadas. La cirugía conservadora en la forma de nefrectomía parcial laparoscópica esta claramente evolucionando, con un aumento de la exigencia al cirujano, requiriendo más especialización y experiencia, con la asistencia añadida de otras especialidades (anestesistas, radiólogos, etc). Para ser capaz de realizar regularmente la nefrectomía parcial laparoscópica sin isquemia de una forma segura, el laparoscopista debe desarrollar su experiencia de una forma gradual, quizás comenzando con clampaje sólo arterial, dando paso a desclampaje precoz y después a clampaje “a demanda”(AU)

La selección del paciente es primordial al progresar a la nefrectomía parcial laparoscópica sin isquemia. El paciente ideal tendría una masa renal única pequeña, polar, exofítica con un riñón contralateral normofuncionante. Aunque actualmente las técnicas y resultados publicados de la nefrectomía parcial laparoscópica sin isquemia se limitan a pocos autores, sin resultados a largo plazo actualmente que demuestren que merezca la pena completamente y sea reproducible, los resultados tempranos son alentadores. Perseguir la adquisición de la isquemia cero merece claramente la pena, pero en necesario medir los riesgos potenciales de aumento de la morbilidad y tasas de márgenes positivos(AU)

The warm ischaemia time appears the most prominent modifiable risk factor for the development of renal impairment following laparoscopic partial nephrectomy. Historically, hilar clamping was the ‘gold standard’ technique, but now we are pushing our techniques to achieve the ultimate: ‘zero ischaemia’ approach. Results from ‘early unclamping’ techniques reinforced the importance of ‘every minute counts’ (28). Subsequent techniques in non-hilar clamping demonstrated that this approach was indeed feasible, but at the expense of higher bleeding, positive margins, and collecting system breach rates. With the advancement of technology, through the use of robotic assistance, improved haemostatic agents, as well as various imaging modalities (laparoscopic ultrasound, CT angiography), the surgeon can now potentially perform Nephron Sparing Surgery (NSS) in a more precise manner. Specifically, with the use of superselective clamping of the feeding vessel(s) to the tumour, the remaining healthy renal parenchyma should be less compromised, with associated low bleeding rates. NSS in the form of laparoscopic partial nephrectomy is clearly evolving, with increasing demands on the surgeon, requiring more expertise and experience, with the added assistance from other specialties (anaesthetists, radiologists etc). To be able to regularly perform Laparoscopic Partial Nephrectomy (LPN) without ischaemia safely, the laparoscopist must develop his / her experience in a stepwise fashion, perhaps commencing with artery-only clamping, leading on to early declamping, and then ‘on demand’ clamping(AU)

When moving on to LPN without ischaemia, patient selection is paramount. The ideal patient would harbour a single small, polar, exophytic renal mass with a normal functioning contralateral kidney. Although currently the techniques and outcomes laparoscopic partial nephrectomy without ischaemia published are limited to a few authors, with no current long term results to prove its full worth and reproducibility, early results are very encouraging. The pursuit of acquiring ‘zero ischaemia’ is clearly worthwhile, but needs to be measured against the potential risks of increased morbidity and positive margin rates(AU)

Sildenafil inhibits the up-regulation of phosphodiesterase type 5 elicited with nicotine and tumour necrosis factor-alpha in cavernosal vascular smooth muscle cells: mediation by superoxide.

OBJECTIVES: To determine whether there is an association between vascular phosphodiesterase type 5 (PDE-5) and NADPH oxidase (NOX) in cavernosal vascular smooth muscle cells (CVSMCs), and to study the actions of the PDE-5 inhibitor sildenafil; the pro-erectile actions of nitric oxide (NO) are reduced by PDE-5 which hydrolyses cGMP to inactive GMP, thus an up-regulation of PDE-5 and over-production of O(2)(-) derived from NOX might promote erectile dysfunction (ED). MATERIALS AND METHODS: To study the effects of nicotine and tumour necrosis factor-alpha (TNF-alpha) on superoxide (O(2)(-)) production and PDE-5 expression, CVSMCs from rabbit penis were incubated with nicotine or TNF-alpha, and superoxide dismutase (SOD), catalase, sildenafil citrate, or apocynin (NADPH inhibitor) for 16 h. The expression of PDE-5 and of glyceraldehyde-3-phosphate dehydrogenase (internal standard) was assessed using Western blotting. O(2)(-) was measured spectrophotometrically. RESULTS: After a 16-h incubation, both nicotine (maximal at 10 microm) and TNF-alpha (10 ng/mL) significantly increased O(2)(-) formation in CVSMCs; this effect was blocked by co-incubating with SOD, catalase, and sildenafil (1 microm). Apocynin also inhibited O(2)(-) formation when added after 16-h incubation with nicotine (10 microm) or TNF-alpha. PDE-5 expression was also significantly increased in CVSMCs incubated with nicotine and TNF-alpha. This effect was negated by 16-h co-incubation with SOD, catalase, apocynin, and sildenafil. CONCLUSIONS: Nicotine and TNF-alpha up-regulate PDE-5 expression in CVSMCs through an a priori up-regulation of NOX and formation of O(2)(-). As PDE-5 hydrolyses cGMP, this effect might 'blunt' the pro-erectile actions of NO. Sildenafil inhibits O(2)(-) formation, and 'normalizes' PDE-5 expression. This represents a novel pathogenic mechanism underlying ED, and a novel mechanism of action of sildenafil.