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reperfusion injury following ischemia for nephron sparing surgery
13th Meeting of the EAU Section of Oncological Urology (ESOU)
Perfusion/reperfusion injury following ischemia for nephron sparing surgery G. Janetschek, Salzburg (AT) Open surgical partial nephrectomy is usually performed in ischemia to allow for precise tumour excision and reconstruction of the renal parenchyma in a bloodless field. Indy Gill (2002) was the first to show that these principles of open surgery can be duplicated by means of laparoscopy. Long standing ischemia compromises renal function due to the reperfusion injury, and a warm ischemia time not longer than 20 – 30 minutes is now considered safe. However, this is true only for patients with uncompromised kidney function, whereas in a patient with a solitary kidney and renal insufficiency 20 minutes of warm ischemia may result in the need for acute or even permanent dialysis. When studying the early reports on laparoscopic partial nephrectomy, two observations can be made. Almost all surgeries were performed in patients with a normal contralateral kidney, so that the problem of ischemia time could be neglected without obvious consequences. On the other hand, when comparing laparoscopy with open surgery, ischemia time was clearly longer even in experienced hands. With growing experience we now have learned to overcome the problem of ischemia time by a series of technical modifications resulting in a substantial decrease of the time required for excision of the tumour, haemostasis, and reconstruction of the parenchyma. Complete or almost complete mobilisation of the kidney during standard laparoscopy allows achieving a perfect geometric situation, so that the straight instruments can be brought in an ideal angle for excision and reconstruction according to the location of the tumour. This situation is greatly facilitated by the increased degrees of freedoms provided by the daVinci robot (Intuitive). An interesting alternative therefore are handheld motorized instruments (Dexterite/France) providing the same degrees of freedom as the daVinci robot. As a next step, the time consuming knotting was replaced by placing clips instead. The large clips (Hem-o-lok®) used for the approximation of the renal parenchyma have the additional advantage that they avoid the suture cutting through the parenchyma when tension is applied. Interestingly, open surgeons performing kidney surgeries are now copying this new technique. A very important step forward was the introduction of the early declamping technique (Baumert 2007). Ischemia is terminated after completion of the suture of the interstitial tissue, and the reconstruction of the parenchyma follows without pressure of time. This technique has another important advantage. Unligated bleeding vessels become obvious after reperfusion, and can be located and therefore ligated precisely prior to the reconstruction of the parenchyma. It has become our standard technique to always terminate ischemia after not longer than 20 minutes, and we were always able without any exception to control a bleeding occurring at this step with an additional interstitial suture. Cooling of the kidney, which is standard in open surgery using ice slush, allows prolonging safe ischemia time. Ice slush can be used during laparoscopy as well. However, the introduction of the ice as well as the protection of the surrounding tissues is technically difficult and awkward, so that it’s use never became popular. Cooling can also be achieved via perfusion of the collecting system with cold saline, a technique familiar to the urologists. There are several drawbacks, however. The surface of the collecting system is small, rendering cooling inefficient. In addition, the medulla and not the cortex is cooled. And as soon as the collecting system is opened, which may occur quite early during excision of the tumour, the cold liquid escapes preventing further cooling. Hypothermia by means of art arterial perfusion is efficient and reliable (Janetschek 2004). There is a 2-fold mechanism of renal protection. In addition to renal hypothermia toxic radicals are continuously washed out, preventing reperfusion injury. However, a radiologist is required to place the angiocatheter prior to surgery, and the catheter may become displaced during the transport from radiology to the OR. In fact, due the short ischemia time realised with the aforementioned technical modifications, we had no need for cold ischemia during the last years.
13th Meeting of the EAU Section of Oncological Urology (ESOU)
Regional ischemia limits the interruption of the blood flow to the area where the tumour has to be excised, and the majority of the kidney is spared to reperfusion injury. In most cases angio –CT/MRI allows to visualize the vessel feeding the tumour, which is then identified during surgery to be clamped or clipped. This technique is very helpful for the bloodless excision of large infiltrating tumours on the convexity of the kidney. The additional use of indocyanine green (ICG) helps to delineate perfused from nonperfused areas. The first laparoscopic partial nephrectomies were performed without ischemia, and haemostasis was mainly based on electrocoagulation (Janetschek 1998). Also other devices such as ultrasonic scalpel, radiofrequency, and a microwave tissue coagulator have been used for this purpose. The main problem with this technique is not haemostasis, however. Because of ongoing burning and charring of the tissue in addition to continuous bleeding, it becomes difficult and even impossible to distinguish between normal parenchyma and tumour tissue so that a negative surgical margin cannot always be achieved in a controlled manner. This technique is limited to small and mainly exophytic tumours. By comparison, “Zero ischemia” partial nephrectomy, a recently developed technique that is especially suited for hilar tumours, follows a different concept (Gill 2011). It requires meticulous dissection of the hilar vessels as a first step. We prefer to secure the hilar vessels with an arterial and venous tourniquet so that ischemia can be initiated immediately when required. Next, all and even the smallest vessels feeding the tumour are identified, clipped and transected, resulting in a step-by-step excision of the tumour. Ideally, this excision is almost bloodless. This technique has several advantages. Reperfusion injury is completely avoided. The precise stepwise excision of the tumour follows a plane close to the tumour so that only a small proportion of healthy uninvolved renal parenchyma is removed together with the tumour. At completion of the excision, haemostasis is already complete avoiding further potentially damaging sutures. The same is true for the following reconstruction of the parenchyma, which becomes easy in this situation. In summary, reperfusion injury of the renal parenchyma can be greatly reduced by a short ischemia time and replacement of complete ischemia by regional ischemia or the zero ischemia technique. Also we have to be aware that the reperfusion injury is not the only damage induced to the renal parenchyma during partial nephrectomy, but deep parenchymal sutures as well as the excision of a large rim of healthy tissue may have more detrimental consequences. Eur Urol Suppl 2016;15(2):38
Perfusion/reperfusion injury following ischemia for nephron sparing surgery G. Janetschek, Salzburg (AT) Open surgical partial nephrectomy is usually performed in ischemia to allow for precise tumour excision and reconstruction of the renal parenchyma in a bloodless field. Indy Gill (2002) was the first to show that these principles of open surgery can be duplicated by means of laparoscopy. Long standing ischemia compromises renal function due to the reperfusion injury, and a warm ischemia time not longer than 20 – 30 minutes is now considered safe. However, this is true only for patients with uncompromised kidney function, whereas in a patient with a solitary kidney and renal insufficiency 20 minutes of warm ischemia may result in the need for acute or even permanent dialysis. When studying the early reports on laparoscopic partial nephrectomy, two observations can be made. Almost all surgeries were performed in patients with a normal contralateral kidney, so that the problem of ischemia time could be neglected without obvious consequences. On the other hand, when comparing laparoscopy with open surgery, ischemia time was clearly longer even in experienced hands. With growing experience we now have learned to overcome the problem of ischemia time by a series of technical modifications resulting in a substantial decrease of the time required for excision of the tumour, haemostasis, and reconstruction of the parenchyma. Complete or almost complete mobilisation of the kidney during standard laparoscopy allows achieving a perfect geometric situation, so that the straight instruments can be brought in an ideal angle for excision and reconstruction according to the location of the tumour. This situation is greatly facilitated by the increased degrees of freedoms provided by the daVinci robot (Intuitive). An interesting alternative therefore are handheld motorized instruments (Dexterite/France) providing the same degrees of freedom as the daVinci robot. As a next step, the time consuming knotting was replaced by placing clips instead. The large clips (Hem-o-lok®) used for the approximation of the renal parenchyma have the additional advantage that they avoid the suture cutting through the parenchyma when tension is applied. Interestingly, open surgeons performing kidney surgeries are now copying this new technique. A very important step forward was the introduction of the early declamping technique (Baumert 2007). Ischemia is terminated after completion of the suture of the interstitial tissue, and the reconstruction of the parenchyma follows without pressure of time. This technique has another important advantage. Unligated bleeding vessels become obvious after reperfusion, and can be located and therefore ligated precisely prior to the reconstruction of the parenchyma. It has become our standard technique to always terminate ischemia after not longer than 20 minutes, and we were always able without any exception to control a bleeding occurring at this step with an additional interstitial suture. Cooling of the kidney, which is standard in open surgery using ice slush, allows prolonging safe ischemia time. Ice slush can be used during laparoscopy as well. However, the introduction of the ice as well as the protection of the surrounding tissues is technically difficult and awkward, so that it’s use never became popular. Cooling can also be achieved via perfusion of the collecting system with cold saline, a technique familiar to the urologists. There are several drawbacks, however. The surface of the collecting system is small, rendering cooling inefficient. In addition, the medulla and not the cortex is cooled. And as soon as the collecting system is opened, which may occur quite early during excision of the tumour, the cold liquid escapes preventing further cooling. Hypothermia by means of art arterial perfusion is efficient and reliable (Janetschek 2004). There is a 2-fold mechanism of renal protection. In addition to renal hypothermia toxic radicals are continuously washed out, preventing reperfusion injury. However, a radiologist is required to place the angiocatheter prior to surgery, and the catheter may become displaced during the transport from radiology to the OR. In fact, due the short ischemia time realised with the aforementioned technical modifications, we had no need for cold ischemia during the last years.
13th Meeting of the EAU Section of Oncological Urology (ESOU)
Regional ischemia limits the interruption of the blood flow to the area where the tumour has to be excised, and the majority of the kidney is spared to reperfusion injury. In most cases angio –CT/MRI allows to visualize the vessel feeding the tumour, which is then identified during surgery to be clamped or clipped. This technique is very helpful for the bloodless excision of large infiltrating tumours on the convexity of the kidney. The additional use of indocyanine green (ICG) helps to delineate perfused from nonperfused areas. The first laparoscopic partial nephrectomies were performed without ischemia, and haemostasis was mainly based on electrocoagulation (Janetschek 1998). Also other devices such as ultrasonic scalpel, radiofrequency, and a microwave tissue coagulator have been used for this purpose. The main problem with this technique is not haemostasis, however. Because of ongoing burning and charring of the tissue in addition to continuous bleeding, it becomes difficult and even impossible to distinguish between normal parenchyma and tumour tissue so that a negative surgical margin cannot always be achieved in a controlled manner. This technique is limited to small and mainly exophytic tumours. By comparison, “Zero ischemia” partial nephrectomy, a recently developed technique that is especially suited for hilar tumours, follows a different concept (Gill 2011). It requires meticulous dissection of the hilar vessels as a first step. We prefer to secure the hilar vessels with an arterial and venous tourniquet so that ischemia can be initiated immediately when required. Next, all and even the smallest vessels feeding the tumour are identified, clipped and transected, resulting in a step-by-step excision of the tumour. Ideally, this excision is almost bloodless. This technique has several advantages. Reperfusion injury is completely avoided. The precise stepwise excision of the tumour follows a plane close to the tumour so that only a small proportion of healthy uninvolved renal parenchyma is removed together with the tumour. At completion of the excision, haemostasis is already complete avoiding further potentially damaging sutures. The same is true for the following reconstruction of the parenchyma, which becomes easy in this situation. In summary, reperfusion injury of the renal parenchyma can be greatly reduced by a short ischemia time and replacement of complete ischemia by regional ischemia or the zero ischemia technique. Also we have to be aware that the reperfusion injury is not the only damage induced to the renal parenchyma during partial nephrectomy, but deep parenchymal sutures as well as the excision of a large rim of healthy tissue may have more detrimental consequences. Eur Urol Suppl 2016;15(2):38