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< Vol. 84 Issue 1 | Jan-Mar 2017 | pp. 1 - 64

Optimising renal cancer patients for nephron-sparing surgery: a review of pre-operative considerations and peri-operative techniques for partial nephrectomy

Optimising renal cancer patients for nephron-sparing surgery: a review of pre-operative considerations and peri-operative techniques for partial nephrectomy

Urologia 2017; 84(1): 20 - 27

Article Type: REVIEW

DOI:10.5301/uro.5000208

Authors

Hani Ertemi, Pramit Khetrapal, Nevil M. Pavithran, Faiz Mumtaz

Abstract

Partial nephrectomy is the gold standard treatment for T1a renal tumours, with some evidence suggesting that T1b could also be amenable to this approach. However, multiple factors affect the perioperative outcome, including modifiable and nonmodifiable risk factors.

Renal function after partial nephrectomy depends on multiple factors, namely pre-operative [baseline kidney function, diabetes, hypertension, high body mass index (BMI), older age and smoking] and intraoperative factors (amount of kidney preserved, ischaemia time). Warm ischemia time should not exceed 25 min, but some evidence suggests that this can be safely extended using cold ischemia.

We discuss various pharmaceutical and pre-operative precautions described in the literature to optimise postoperative kidney function, and surgical approaches using open, laparoscopic and robotic techniques. Novel techniques such as selective clamping and zero ischaemia time are promising options with a potential benefit in this area. However, further studies are needed to establish their role in partial nephrectomy. Transperitoneal and retroperitoneal approaches have been used, with the transperitoneal approach being used more commonly. A retroperitoneal approach may have a role in nephron-sparing surgery depending on the location of the tumour.

Conclusions

Nonmodifiable factors including pre-operative renal function and amount of healthy renal tissue preserved are the most important predictive factors that determine renal function after partial nephrectomy. Ischaemia time is an important modifiable risk factor and cold ischaemia time should be used if longer ischaemia time is anticipated. New techniques may have a role in maximising postoperative kidney function, but more robust studies are required to understand their potential benefits and risks.

Article History

  • • Accepted on 27/11/2016
  • • Available online on 16/01/2017
  • • Published in print on 03/02/2017

Disclosures

Financial support: The authors received no financial support for the research.
Conflict of interest: The authors declare that there are no conflicts of interest.

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Introduction

The incidence of renal cell cancer (RCC) has increased over the last few decades, especially in urban populations. With a peak incidence of RCC in the sixth decade of life, many patients present with multiple comorbidities, further complicating surgery. With the increased availability of computed tomography (CT) and magnetic resonance imaging (MRI) scanning, more renal tumours are being identified before patients are symptomatic, and these tumours tend to be smaller in size. Volpe et al (1) found that only a small percentage of smaller, asymptomatic renal masses presumed to be renal cell carcinoma grow significantly if managed conservatively. This, and the availability of nephron-sparing surgery, means that more patients and surgeons are opting for partial nephrectomies for definitive treatment.

With the oncological outcome of partial nephrectomy (PN) and radical nephrectomy (RN) being equivalent (2, 3), PN is now considered as the gold standard for small localised renal tumour (T1a). There is now evidence that PN has acceptable oncological outcome for larger localised (T1b) tumours (4, 5). Furthermore, there is strong evidence to suggest that renal function is far better preserved with PN than RN (6), as recently confirmed by the EORTC randomised trial (7).

Ischaemia time is an important variable in nephron-sparing surgery, as longer ischaemia time is associated with a drop in postoperative renal function. Lane et al (8) found that renal ischaemia under 20 min is not associated with clinically relevant functional loss compared with cold ischaemia time. On the contrary, warm ischaemia time of more than 10 min had a significant (11%) drop in glomerular filtration rate (GFR) in the long term, but immediate postoperative GFR was unaffected in ischaemia time of up to 20 min. Ischaemia times longer than 20 min resulted in both postoperative and long-term drop in GFR.

Simmons et al (9) found that long-term renal function after PN was less affected by intraoperative ischaemic time than immediate postoperative renal function. In contrast, the amount of resected tissue affects long-term and immediate renal function in a similar way. Both these factors affect patients developing chronic kidney disease (CKD), or worsening their known CKD, as a result of their surgery. It is common practice to clamp the renal vessels at the time of PN. This offers several advantages including better visualisation of the tumour that minimises the amount of healthy tissue removed, better access to the intrarenal system by reducing renal tissue turgor, facilitating the parenchymal closure and above all, reducing the intraoperative bleeding. That also carries an ischaemic damage to the kidney with possible deterioration of kidney function postoperatively. Various factors may affect the RF after PN that including nonsurgical (pre-operative eGFR, age, sex, presence of single functioning kidney) and surgical (ischaemia time and type, surgical approach and type of clamping). Some drugs such as mannitol, allopurinol and pioglitazone have also been described as nephro-protective agents.

Pathophysiology of renal injury

Ischaemia time is considered one of the main factors affecting residual renal function post-NSS, alongside the amount of renal parenchyma preserved. The type and duration of ischaemic insult to the kidney will be discussed in other sections and we will focus on the cellular mechanisms of damage in this section.

Ischaemia-reperfusion injuries are thought to be caused by an inflammatory response after the ischaemic insult to the kidney. This leads to vasoconstriction and vascular congestion, which further worsens the ischaemia. Adenosine triphosphate (ATP) depletion activates harmful enzymes (proteases and phospholipases) that cause oxidant injury to tubular cells and endothelial cells of peritubular capillaries upon re-perfusion. This results in vasoconstriction, and further ischaemia and expression of adhesion molecules that initiate leukocyte infiltration. This starts the inflammatory processes with the release of cytotoxic cytokines, reactive oxygen species and proteolytic enzymes that damage tubular cells (10). Factors such as tumour necrosis factor (TNF)-alpha (11) and interleukin (IL)-8 (12) amplify this process by inducing apoptosis and attracting additional leukocytes that further release cytotoxic cytokines.

Weight et al (13) published about renal ischaemia-reperfusion injury in the context of transplant surgery, but it is very relevant to nephron-sparing surgery as well. Renal ischaemia results in generation of hypoxanthine due to ATP depletion, which leads to the production of uric acid and free radicals. Free radicals cause extensive damage to the renal cell, with one of the major reactions thought to be the peroxidation of the lipid membrane.

Endothelin to nitric oxide ratio is altered in ischaemia, where endothelin acts to vasoconstrict vessels and nitric oxide acts to reverse this phenomenon. The renal vasculature is approximately 10 times more sensitive to the effects of endothelin than other vascular beds (14). This particularly affects the outer medulla where tubules have a high oxygen demand. This is not only thought to be partly a product of the ischaemia but also further worsened by leukocyte-endothelial cell interactions and coagulation pathways (15). Nitric oxide could have a protective role on the kidney, or at least one that enables recovery post-ischaemia (16).

The intracellular environment is rich in potassium and low in sodium and this ratio is maintained by ATP-dependent Na+-K+ ATPase pump. During ischaemia, this ATP is unavailable for this ratio to be maintained and this results in swelling of the renal cells. Cellular potassium and magnesium are lost, calcium enters the cell, anaerobic respiration and resulting acidosis triggers lysosomal enzymes, initiating cell death (17). During reperfusion, hypoxanthine is oxidised to xanthine, generating free radicals that cause further cell damage. Endothelial injury leads to swelling, which contributes to the production of local factors promoting vasoconstriction and adds to the effects of vasoconstriction and tubule cell metabolism by physically impeding blood flow, perpetuating that vicious cycle.

It is important to consider that it is not just the ischaemia that causes cellular injury but also the reperfusion, and both processes need to be considered to minimise damage to the kidney. Reperfusion following ischaemia produces an inflammatory response that worsens the damage caused to the kidney by the ischaemia. This is largely secondary to superoxide species being produced by the conversion of xanthine dehydrogenase to xanthine oxidase and other cellular processes. These superoxides lead to the production of hydroxyl radicals as well as reactive oxygen species, and reacting with nitric oxide producing peroxynitrite. These processes lead to the consumption of antioxidant substrates and reduce overall cell activity (18).

Factors affecting patient optimisation

McKiernan et al (19) found that patients undergoing surgery for RCC are more likely to have hypertension, diabetes, advanced age and to have a smoking history than their counterparts undergoing transplant donation surgery. They reported that among patients undergoing RN and PN, 43% and 48% of the patients had a diagnosis of hypertension, 46% and 47% of patients had a smoking history, and 9% and 9% of patients had diabetes, respectively. Comorbidities also have an effect on surgical outcome, with systemic diseases such as hypertension and diabetes having a negative effect on postsurgical renal function.

Malcolm et al (20) compared patients with diabetes, hypertension, having a BMI of >30, age >60 and smoking as risk factors in patients undergoing RN or PN with patients without these comorbidities in 749 patients, and found that all these risk factors were associated with postoperative creatinine increase, low eGFR and metabolic acidosis in this group. Even a small elevation in blood pressure (BP) is an independent risk factor for end-stage renal disease (21), and this risk is worsened with a reduction in renal parenchyma. As these are all risk factors for CKD, undergoing surgery that reduces renal mass compounds the risk of worsening their CKD.

These factors can potentially be improved pre-operatively to improve postsurgical outcomes in theory, but often these procedures are done under time pressure such as a probable or confirmed diagnosis of cancer.

Novel solutions

Waller et al (22) have evaluated oxidative damage using an isolated organ perfusion model of transplanted kidney, demonstrating that 8-isoprostane level was a good biomarker prediction for oxidative stress damage. Keel et al (23) further studied this in the animal model. They found that allopurinol given pre-operatively in rats reduced the post-ischaemia spike in their 8-isoprostane levels, a marker of renal ischaemia, which usually goes up by 3.2 times following 60 min of renal artery clamping. Hyperuricaemia is also thought to worsen CKD, and use of allopurinol in transplant patients improved long-term kidney function in patients with known hyperuricaemia, even if it is asymptomatic (24). This should translate to partial nephrectomies, and it may be worth monitoring uric acid levels closely postoperatively for careful preservation of the remaining renal tissue.

Mannitol was also studied as a prospective nephroprotective agent, as it is widely used for its antioxidant and anti-inflammatory properties. Mannitol’s role in this is attributed to its effect of decreasing intravascular cellular swelling, free radical scavenging, decreasing renin production and increasing intravascular volume. However, there is no clear consensus if mannitol has any functional effect on renal function after ischaemic stress. Khoury et al (25) studied this in the rat model and found that mannitol can reduce the disturbance of the oxidant-antioxidant balance caused by ischaemia, but more data and research are required to assess if there is any functional change. Power et al (26) found that although mannitol increased diuresis post-PN, there was no significant change to renal function at any stage for 6 months postoperatively. The rationale behind using diuretics includes maintaining non-oliguric state by promoting dieresis and preventing tubular obstruction. This also reduces medullary oxygen consumption and increases renal blood flow (27). In a survey including 92 high volume centres for PN, 78% of the centres used Mannitol intraoperatively; the indication according to the survey was antioxidants (21%), diuretic (5%) and as of two (74%) (28).

Hu et al (29) studied the effect of pioglitazone in the mice model and found that animals pre-treated with pioglitazone had lower plasma levels of blood urea nitrogen and creatinine, lower histopathologic scores and improved survival rates after renal ischaemic injury. Prior to this, Kakadiya et al (30) had found that pioglitazone improved postoperative renal function in rats after intraoperative ischaemia, but these findings are specific to diabetic rats. This effect needs to be studied in humans through further studies.

Hu et al (29) studied the protective effect of Pioglitazone on renal reperfusion injury; in an experimental study, mice were randomised into two groups, one was pre-treated with pioglitazone after which both were subjected to bilateral renal ischemia for 45 min; the effect of the reperfusion injury was assessed by means of serum creatinine and histopathologic examination. Animals that were pre-treated with pioglitazone had lower serum urea and creatinine, lower histopathologic score and better survival.

The use of various medical strategies to reduce the effect of renal ischemia has been mentioned in experimental and clinical practice. As previously described, ischaemia time causes renal injury by organ-induced ischemia and ischaemia reperfusion injury.

It has been suggested that the use of angiotensin-converting enzyme (ACE) inhibitors such as enalapril IV can have a renal protective effect. It is meant to induce renal vasodilatation and prevent vasospasm that might be caused by manipulation during surgery (2). Other vasodilatory substances such as diltiazem and dopamine have been used in animal studies to increase renal blood flow and protect against renal ischemic injury, but their efficacy is doubtful (31). To prevent vessel thrombosis, it has been suggested that heparin could be administered before applying the clamp (32).

It is of paramount importance to maintain the BP during surgery within the normal range with systolic BP above 120 mm Hg and mean arterial pressure above 80 mm Hg, which will allow good renal perfusion during intraoperative time.

Comorbidities are relatively unmodifiable factors contributing to ischaemic insult during nephron-sparing surgery, but novel therapies such as those outlined above may provide a degree of benefit to postoperative renal function in the future.

Pre-operative eGFR as an assessor predictor for renal function

The most common way to assess renal function in clinical practice is to use serum creatinine; however, the level of serum creatinine varies widely and is influenced by other factors, including age, sex and muscle mass. It was estimated that patients with normal serum creatinine, renal mass and normal contralateral kidney have at least 25% risk of moderate CKD (GFR <60 ml/min per 1.73m2) (6). The use of GFR calculated by 24-hour creatinine clearance or eGFR can provide a more reliable way to assess renal function (33). eGFR can also predict the renal function after surgery. In a study involving 1169 patients, Lane et al. showed that 3.6% of the entire cohort developed acute renal failure postoperatively; however, the percentage varies considerably depending on the preoperative eGFR, with 0.8%, 6.2%, 34% developing ARF for normal renal function, stage 3 CKD and stage 4 CKD, respectively. In the long run, 2.5% of the entire cohort developed end-stage renal disease; again, this percentage changed according to preoperative eGFR with up to 36% of patients with stage 4 CKD compared with only 0.1% for patients with pre-operative normal renal function (34).

The use of renal scintigraphy, namely the use of technetium TC 99m Mercapto-acetyl-triglycine (99mTC-MAG-3), remains the most sensitive way to assess that amount of renal function lost after surgery and is considered superior to the clearance of chromium 51-ethylene diamine tetra acetic acid (51Cr-EDTA) (35). However, this test is considered too costly and invasive and its use has been limited.

Ischaemia time

Experimental models

Several animal studies have been carried out to determine the safe limit of renal ischemia, but results are contradictory (36). A study by Ward et al (37) on dogs concluded that 30 min is the safe limit for renal ischaemia, as this was followed by full recovery of renal function. However, other studies showed that 30 min is not necessarily a cut-off; Laven et al (38) demonstrated renal resistance to warm ischaemia (WI), open partial nephrectomy (OPN), warm ischaemia time (WIT), cold ischaemia time (CIT), cold ischaemia(CI), laparoscopic partial nephrectomy (LPN) beyond the traditionally accepted 30 min in a solitary kidney pig model. Prolonged renal WI time increased the incidence of renal dysfunction during the initial 72 h after the ischaemic insult. However, by 2 weeks after the WI insult, renal function returned to baseline in the 30, 60 and 90-min WI groups.

Type of ischaemia

There is strong evidence in the literature of the superiority of cold ischemia compared with warm ischaemia in regard of postoperative renal function injury (39, 40). There are various ways of achieving cold ischemia. Lying ice slush is the most common way in OPN, has been described for LPN and is generally advised if the WIT is expected to exceed 20 min. After initial cooling for 10 min, CIT for up to 35 min has been demonstrated (41, 42).

In a study involving 660 patients who underwent OPN in a solitary kidney (300 WI and 360 CI), the eGFR decreased by similar amounts in both groups despite the fact that CI time was much longer (45 versus 22 min). The conclusion from this study was that although postoperative renal function was primarily determined by the quality and quantity of renal parenchymal preserved, the type and duration of the ischaemia remain the most important modifiable factors (39).

Intra-arterial cooling is another technique that has been described to achieve more homogenous hypothermia, using Ringer’s lactate that can allow cooling up to 5-10oC (43).

Renal ischaemia in solitary kidney

PN in a solitary kidney has always been considered an ideal way to assess the effect of renal ischemia on postoperative renal function, as this will not be affected by compensatory changes in the other kidney. However, it has been argued that a single kidney may be more resistant to renal ischemia, making the results nonapplicable to patients with two kidneys (44). Thompson et al (42) studied 537 patients who underwent open PN: 85 did not require vascular clamping, 174 had WIT and 278 had CIT. The results showed that WIT and CIT were associated with a higher risk of acute and chronic renal failure and temporary dialysis. Furthermore, patients with WIT >20 min and CIT >35 min had a higher incidence of acute kidney injury. Lane et al (39) analysed 660 patients who underwent open PN; the results showed that age, tumour size, ischaemia time and lower preoperative eGFR were all associated with a decrease in postoperative eGFR. Interestingly, incorporating the parenchyma spared into the analysis changed statistical significance, making preoperative eGFR and percentage of the parenchyma the only two relevant factors and rendering the ischaemia time insignificant.

Renal ischaemia in bilateral kidneys

The postoperative renal function after PN in the presence of normal contralateral kidney is influenced by compensatory hypertrophy changes, which can mask the functional loss of the affected kidney. The use of renal scintigraphy can demonstrate the percentage of renal function loss, which can be more informative that serum creatinine or eGFR, which can only reflect the global renal function.

Porpiglia et al (45) prospectively studied the postoperative renal function in 18 patients who underwent LPN by 99mTC-MAG-3 renal scintigraphy. They demonstrated that the overall renal function did not change significantly postoperatively. However, the split function that was 48% dropped to 36.9% on day 5 only to recover to 42.8% after 1 year. The authors concluded that amount of parenchymal preserved and WIT >32 min are the most significant factors to predict renal outcome.

Godoy et al (46) studied 101 patients who underwent LPN and showed that 40 min of WIT seems to be an appropriate cut-off. In this study, the incidence of renal function impairment was more than two-fold higher in those with a warm ischaemia time of greater than 40 min than in the other groups; the pre-operative eGFR was the only independent predictor of an increased risk of renal insufficiency following laparoscopic PN.

Surgical techniques

Open, laparoscopic and robotic approach

Open PN has long been considered the gold standard operation for localised renal tumour; it does provide an acceptable ischaemia time and it allows every possible ischaemic approach without additional technical complexity. Even if larger tumour resection can be performed in 20 min of WIT (2), particularly in case of solitary kidneys, open technique provides the safest surgical access with the best postoperative function (47). However, the morbidity associated with open surgery together with the improvement and growing experience in laparoscopic technique, laparoscopic nephrectomy became more feasible. A study involving 1800 patients (48) (771 open and 1029 laparoscopic) demonstrated that LPN had a shorter operating time, shorter hospital stays and less blood loss. It was associated with longer WIT and postoperative complications, but the functional and oncological outcome were similar in both groups. However, this was not a randomised trial and patients in the OPN group had larger tumours and worse performance status.

It has been suggested that pneumoperitoneum might exert a protective effect against ischemia during PN. Bhayani et al (49) compared the outcome of renal function on the basis of serum creatinine in 118 patients who underwent LPN for single unilateral tumour with a normal contralateral kidney; the study concluded that ischaemia time up to 55 min did not affect the functional outcome. The use of serum creatinine in this study may limit its credibility. Adamy et al (50) used eGFR instead to assess the functional outcome following PN, in a study including 987 patients who were treated by LPN (182) and OPN (805). Patients who had LPN maintained a slightly better eGFR than the open group. Given the technical difficulty in performing LPN, especially performing the internal renorrhaphy, it is plausible to assume that the ischaemia time will be longer and that will affect the renal function after surgery. Various studies comparing the two techniques revealed a longer ischaemia time in LPN group; in a comparative study by Lane et al (51), 169 open and 30 laparoscopic partial nephrectomies were performed for 7 cm or smaller tumours in a solitary functioning kidney; the WIT was 9 min longer and more patients need dialysis after the LPN. In another multi-institutionalised study by Shikanov et al (52), 401 patients underwent LPN with median WIT of 29 min. This study showed that patients with longer WIT had a higher decline in renal function afterward in terms of more drop in eGFR. However, the overall conclusion from this study is that within the range of time (interquartile range: 22-34 min), renal ischaemia did not have a significant impact on the overall renal function in patients who underwent LPN.

The technical difficulty of LPN and morbidity associated with OPN opened the door for robotic technology that carries several advantages from both techniques. In addition of being minimally invasive way, robotic PN (RPN) provides a three-dimensional view, tremor filtration and more precision in various surgical manoeuvres. Another advantage of robotic surgery is the shorter learning curve to reach an ischaemia time <20 min (53).

In a systematic review by Zhang et al (54) comparing RPN to LPN, 14 comparative studies were included involving 1539 patients; parameters such as operative time, estimated blood loss and hospital stay were similar between the two groups; however, RPN had a significantly shorter ischaemia time.

Transperitoneal versus retroperitoneal approach

Although retroperitoneal approach (RPA) has been described by Gaur et al. (55), it seems that it has not adopted widely, and this is can be explained by the smaller working area and the lack of anatomical landmarks making the operation more challenging.

Minimal invasive surgery, both robotic and laparoscopic, has been described using both approaches; the choice of the approach depends mainly on the tumour location with transperitoneal approach (TPA) used mainly for anterior and medial tumours, while the RPA used for the posterior and lateral tumours (56). In a study involving 163 patients including 100 TPA and 63 RPA, Ng et al (57) showed that TPA was associated with longer operating time (3.5 versus 2.9 h) and longer ischemia time (31 versus 28 min) together with longer hospital stay (2.9 versus 2.2 days). However, this can be explained in part that most of the larger tumours were done through the TPA (3.2 versus 2.5 cm). In another study comparing TP versus RP approach, the difference in WIT and LOS were statistically insignificant (Ouzaid et al 2012) (58) and another study by Marszalek et al (59) included 70 patients who underwent RPLN; the OT was much shorter of 80 min, and the WIT was comparable to previous studies (22.6 min).

In robotic surgery, various studies have looked into both approaches. Ellison et al (60) studied 108 patients undergoing transperitoneal robotic PN (TPRPN) and the overall OT was 215 min with WIT of 24.9 min but a positive margin rate of 5.6%. Another study by Haber et al (61) involved 75 patients and showed shorter operating time of 200 min and shorter WIT of 18.2 min with only 1.3% positive margin rate. With growing experience in robotic surgery, the RP approach has been described. In a large multicentre study, Hu et al (62) studied 277 patients who underwent RPRPN; the median operating time and ischaemia time were 165 and 19 min, respectively; hospital stay was 2 days. Twenty-eight patients developed complications of whom three patients required intervention to correct Clavien grade 3 complication, including three patients who need embolisation for pseudoaneurysm.

From the various examples above, it does not seem that either of the two approaches carries any significant benefit. It is understandable that more surgeons opt to use the TPA, as it does provide more operating space and anatomical landmark; however, the anatomical location of the tumour is an important factor that determines which approach is more feasible.

Various techniques have been described during PN to achieve bloodless field and therapy help with the tumour resection; however, no technique has proven to be superior and universally adapted.

En bloc and artery only clamping

The influence of clamping technique on renal function remains unclear in the literature. In animal models, artery-only clamping (AO) in open PN seems to be associated with better RF outcome than artery and vein (AV) clamping; the explanation of this can be due to the retrograde venous blood flow that allows partial oxygenation of the parenchyma (63). Orvieto et al (64) looked at AV versus AO technique using single kidney porcine model with both open and laparoscopic techniques; they reported a better RF outcome with AO clamping in the OPN, which demonstrated lower serum creatinine in the early postoperative days.

In a study by Gong et al (65), 25 patients who underwent AO clamping have been matched to 53 patients who had hilar clamping, although there was no difference in the warm ischaemia time. However, patients with hilar clamping showed a significant increase in postoperative serum creatinine both in the immediate postoperative period and in follow-up, but this change was more pronounced in patients with previous CKD. However, patients with preoperative normal kidney function were also affected.

A meta-analysis published recently by Zhou et al (66) included seven retrospective studies comparing hilar clamping with AO clamping. It showed no difference between the two groups in terms of operative time and length of stay, although the selective clamping group had more estimated blood loss, but there was no difference in the transfusion rate. Furthermore, there was a superior short-term renal function preservation (at week 1 and 3 months).

Parenchymal clamping

In selected patients with polar tumours or exophytic lateral tumour, parenchymal clamping can provide a safe alternative for warm ischaemia, first described by Simon et al (67) with laparoscopic PN. In addition, to avoid renal ischaemia and postoperative reduction in eGFR, Simon’s clamp comes with standard ratchet technique that prevents the clamp from slipping down while providing constant and uniform pressure. The tumour margins status can be inspected carefully without concern of ischaemia time and the bleeding points can be checked while the clamp is released gradually. Viprakasit et al (68) used the same technique in robotic-assisted laparoscopic PN; in a study that included 20 patients, RALPN was successful in 17 patients, and in three patients, the clamp did not control the bleeding and central hilar clamping was necessary. The results showed no positive margin and no drop in eGFR both postoperatively and at median follow-up of 6 months; none of the patients needed blood transfusion.

Segmental artery clamping

Clamping a segmental branch, rather than the main artery, is another technique to reduce global renal ischaemia and improve post-operative renal function outcome; this has become even more feasible with the development of robotic surgery. In a study by Shao et al (2011) (69), a total of 75 patients underwent LPN of whom 38 patients had segmental artery clamping. Although patients with segmental artery clamping have significantly more blood loss and WIT, they had significantly better postoperative renal function, and seven patients had to convert to conventional main artery clamping due to bleeding.

Early unclamping

It was suggested that early release of the clamp after internal renorraphy can significantly reduce the WIT and therapy will improve postoperative renal function. In a study by Nguyen and Gill (70), ischaemia time was reduced by 50% with even lower complication rate.

Zero ischaemia

In an attempt to alleviate renal ischaemia, some surgeons perform tumour resection without clamping, obviously that can result in an unacceptable degree of bleeding and various techniques have been described to reduce this. Ko et al (71) described manual compression during open partial nephrectomy to reduce bleeding. Another study by Gill et al (72) described a novel technique to reduce bleeding in which microdissection of the tertiary or quaternary renal artery that supplies the tumour is identified and ligated, which is performed in combination with pharmacologically induced controlled hypotension. The study included 15 patients with no significant change in renal function postoperatively and no positive margins.

Conclusion

Partial nephrectomy is considered as the gold standard for treating small renal tumours. However, this is usually associated with a degree of renal ischaemia that might affect postoperative renal function. Ischaemia time is a modifiable risk factor; it has been suggested that WIT <25 min is associated with better outcomes, although this can be significantly longer with CIT. Various techniques to reduce ischaemia time have been described, including parenchymal and segmental artery clamping, early unclamping and zero ischemia with varying results. Minimally invasive surgery, including robotic and laparoscopic techniques, has become increasingly popular, but there is no clear evidence to suggest better postoperative renal function with these techniques.

Disclosures

Financial support: The authors received no financial support for the research.
Conflict of interest: The authors declare that there are no conflicts of interest.
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Authors

Affiliations

  • Department of Urology, Basildon and Thurrock University Hospitals NHS Trust, Essex - UK
  • Division of Surgery and Interventional Science, University College London, London - UK
  • Department of Urology, University College London Hospital, London - UK
  • Department of Urology, Royal Free London NHS Foundation Trust, London - UK

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