Renal cell carcinoma. Clinical management. Eric A. Klein (Editor). Springer, 2013
History of nephron-sparing surgery
Renal cell carcinoma (RCC) is a relatively rare tumor that accounts for approximately 3% of adult malignancies. In 2010 approximately 58,240 new cases developed, with close to 13,000 patients dying of the disease. Over the last century the incidence and mortality of RCC has increased for both clinical T1 and T2 disease. Although radical surgery remains the mainstay of treatment for locally advanced disease, recent guidelines encourage the use of nephron-sparing approaches for T1 disease whenever feasible.
The first partial nephrectomy (PN) was performed in 1884 by Wells for removal of a perirenal fibrolipoma. In 1887, Czerny was the first to use PN for excision of a renal neoplasm when he successfully removed an angiosarcoma from the upper third of the right kidney of a gardener. At this time, however, PN was associated with significant complications, including renal bleeding, urinary fistula, and death as compared with total nephrectomy, which had a lower operative morbidity and satisfactory long-term results. In 1950, Vermooten published his techniques and indications for PN and suggested that this procedure could be performed, even in the presence of a normal contralateral kidney. Vermooten suggested that peripheral encapsulated renal neoplasms could be excised locally while leaving a margin of normal parenchyma around the tumor. In the early 1960s, however, Robson et al., established radical nephrectomy (RN) as the treatment of choice for localized RCC, reporting a 66% and 64% overall survival for stage I and II tumors, respectively. These results represented a significant improvement in survival rates when compared with patients treated with simple nephrectomy, and this therapy became the treatment of choice for localized RCC.
Over the last two decades, advances in renal imaging, renal and vascular surgery (such as improved methods for prevention of ischemic renal damage), and the significant increase in the rate of incidentally discovered small renal masses have all driven the renewed enthusiasm for nephron-sparing surgery (NSS). The fact that NSS can be performed safely with low morbidity, good preservation of renal function and sound oncologic outcomes is not debated, however, recent data suggests that NSS continues to be underutilized. This is largely driven by surgeon practice pattern; competing approaches, such as laparoscopic RN, are often favored because of decreased morbidity and lower technical complexity. This chapter outlines the indications, techniques, and outcomes that support NSS as the treatment of choice for localized renal masses.
Indications for nephron-sparing surgery
NSS is the preferred treatment for localized renal masses, particularly in patients at risk of renal dysfunction. Potential indications for this approach include:
- Bilateral synchronous renal masses
- Mass in an anatomically or functionally solitary kidney
- Unilateral mass with a functioning contralateral kidney and any concomitant condition with the potential to adversely impact renal function
- Renal masses in familial and hereditary disease
- Unilateral mass <7 cm with a normal contralateral kidney
- Advanced renal cancer
Bilateral Renal Masses
Early experience with PN was gained in patients with bilateral, synchronous RCC, where the need for preservation of at least a portion of one kidney was obvious. Bilateral renal tumors are reported in 1–5% of patients. In a study from Memorial Sloan-Kettering Cancer Center (MSKCC), investigators identified 46 patients with bilateral tumors (4%) of which 33 (72%) were synchronous and 13 (28%) were asynchronous. The second tumor in the asynchronous group occurred at a median time of 84.5 (28–240) months after diagnosis of the incident tumor. The histological concordance rate was 76% between tumors. In these patients, it is crucial to preserve as much functioning renal tissue as possible. This entails performing bilateral partial nephrectomies whenever possible, usually as staged procedures beginning with the kidney that seems most amenable to PN. When a large tumor on one side precludes PN, the operative sequence is usually to perform the PN first, thereby obviating the need for temporary dialysis in the immediate postoperative period if acute renal injury occurs.
Occasionally a partial rather than RN on the second side is necessary to avoid chronic kidney disease (CKD) when the initial procedure results in a renal remnant of borderline size or function.
Unilateral renal mass with impaired or absent contralateral kidney or concomitant disease processes that can adversely affect renal function
Renal tumors in a functionally or anatomically solitary kidney also necessitate a nephronsparing approach. In these circumstances, it is crucial to counsel patients that temporary or permanent renal replacement therapy may be necessary postoperatively. Generally, a renal remnant with the function of at least 20% is necessary to avoid permanent renal failure. A report from the Cleveland Clinic that represents the largest published experience of renal tumors in solitary kidneys showed that in 323/400 total patients (81%) the absent kidney had been surgically removed and 77 (19%) had a congenitally solitary kidney. In 46% of these patients, evidence of renal insufficiency was present at baseline. Renal hilar clamping was used in 96% of the cases, with a mean tumor size of 4.18 cm. Interestingly, 36% of these patients had multifocal disease and 92% of the tumors were malignant. Postoperatively, 95% had satisfactory long-term renal function. Authors from the same institution compared outcomes of laparoscopic (n = 30) and open PN (n = 169) in solitary kidneys and reported that the laparoscopic cases required longer ischemia times, a greater need for postoperative dialysis, and experienced twice the complication rate than the open approach. They concluded that open PN is safer in these patients at high risk of CKD.
The presence of a unilateral renal tumor with a functionally impaired contralateral kidney is another common indication for NSS. Contralateral functional impairment may be due to a variety of systemic or urologic diseases, including diabetes mellitus, nephrosclerosis, renal artery stenosis, hydronephrosis, chronic pyelonephritis, and vesicoureteral reflux. The clinical and operative considerations in these patients are similar to those with true solitary kidneys.
Unrecognized medical renal disease is another challenge in renal cancer patients. A study from the Harvard Medical School examined the nontumor-bearing kidney of patients undergoing surgery for renal tumors, and reported that only 10% of patients had completely normal tissue adjacent to the tumor, and 90% were found to have vascular sclerotic changes, diabetic nephropathy, glomerular hypertrophy, and diffuse glomerulosclerosis. In these patients, it is crucial to evaluate preoperative renal function not solely based on serum creatinine but also instead with the measurement of urine albumin and estimated glomerular filtration rate (GFR) using equations based on the level of serum creatinine, age, sex and race.
Another indication for NSS is in patients with unilateral tumors and a normally functioning contralateral kidney but with a condition that might threaten future renal function. This includes renal calculi, diabetes mellitus, hypertension, or renal artery disease. The decision to perform a partial rather than an RN in these patients depends on the feasibility of partial resection. However, current guidelines indicate that PN is the default approach whenever feasible.
Renal masses in familial/ hereditary disease
Multifocal and bilateral tumors are common in hereditary and familial tumor syndromes such as von Hippel–Lindau (VHL) disease, hereditary papillary renal cancer, and the Birt–Hogg–Dube syndrome, and can account for 3–5% of all renal cancers. RCC occurs in approximately 45% of patients with VHL. The rationale for a nephron-sparing approach in patients with this disease is based on a younger average age of presentation than sporadic RCC and the propensity for renal tumors in VHL to be multifocal, bilateral, and recurrent. However, because of the multifocal nature of renal tumors in VHL, these patients are at increased risk for developing local recurrences over the long term. In the era of advanced abdominal imaging and genetic screening, most patients are diagnosed with small, asymptomatic renal tumors. Intervention is generally recommended before an individual tumor exceeds 3 cm in diameter, after which point there is a risk for developing metastatic disease.
Unilateral renal cell carcinoma with normal contralateral kidney
Refinements in imaging techniques have enhanced the detection of early stage, incidental renal masses and have contributed to an increasing role of NSS in patients with localized disease and a contralateral normal kidney. Extended experience has established that NSS can be performed safely with minimal morbidity, preservation of renal function, and long-term survival in patients with small, incidental renal masses. Multiple reports have shown that PN results in survival rates equivalent to those achieved after RN for T1 disease.
The more recent expansion of the indications for NSS includes patients with renal masses 4–7 cm in diameter in anatomically favorable locations. A recently published study which combined patients from the Mayo Clinic and MSKCC evaluated 1,159 patients with renal tumors 4–7 cm in size. There was no significant difference in survival between patients treated with RN or NSS. A more recent study from MSKCC reported on the use of NSS in tumors >7 cm in diameter with favorable outcomes. This study confirmed that tumor size should not restrict the use of NSS, but rather tumor location, careful case selection, and tumor biology are more critical factors. In addition, the amount of remaining functional renal tissue should guide the use of NSS in patients with renal masses greater than 7 cm.
Advanced renal cell carcinoma
The use of PN in the setting of advanced RCC has not been extensively addressed. Angermeier et al. reported on nine patients who underwent PN for RCC with venous involvement in a solitary functioning kidney. Complete tumor resection and preservation of renal function was achieved in all cases, although recurrence rates were significantly higher than for low-stage disease. Currently, surgical resection after systemic therapy (e.g., mTOR and tyrosine kinase inhibitors) can be considered as part of a multimodal approach. Cleveland Clinic researchers reported on 19 patients treated with systemic targeted therapies (sunitinib, bevacizumab/interleukin-2) followed by surgical resection in cases of stable disease or a partial clinical response. In the subset of patients who subsequently underwent PN after tumor downsizing, no substantial complications were encountered despite the potential impact of these agents on wound healing and vascular integrity. These clinical scenarios will be encountered more frequently as the use of systemic therapy in locally advanced disease expands.
Techniques of nephron-sparing surgery for renal cell carcinoma
Although RN is considered optimum curative therapy for patients with locally advanced RCC, PN is the treatment of choice for T1 carcinomas. In such patients, PN allows complete surgical excision of the primary tumor while preserving sufficient renal parenchyma to avoid future renal dysfunction. A variety of surgical techniques are available for performing PN in patients with RCC. All of these techniques require adherence to basic principles of early vascular control, avoidance of ischemic renal damage, complete tumor excision with negative margins, precise closure of the collecting system, careful hemostasis, and bolstering of the renal defect with adjacent fat, peritoneum, or hemostatic agents. At its origin, laparoscopic PN was developed to replicate the open surgical approach, so as a result these techniques share several similarities. We describe the common characteristics below.
Selection of open versus minimally invasive nephron-sparing surgery
The first report of laparoscopic PN for malignancy was only 2 years after the original description of laparoscopic nephrectomy by Clayman. Widespread adoption of minimally invasive PN, though, has been hindered by competition from laparoscopic RN and ablative therapies as well as the increased technical expertise required for the often complex intracorporeal reconstruction necessary during laparoscopic PN. Recent data suggests that robotic assistance may lower this barrier, making laparoscopic management of small renal masses more accessible to urologists and their patients. However, a solid laparoscopic foundation is important to the adoption of robotic-assisted PN. Surgeons must determine which approach to PN in their hands will provide the best oncologic and functional outcomes for their patients based on the preoperative patient and tumor characteristics. Surgeons with experience performing both open and minimally invasive NSS can select the best approach for individual patients and tumors on a case-by-case basis. Surgeons with a greater comfort level with one approach over another must consider whether their skills match the needs of their patient.
In our experience, minimally invasive NSS (e.g., laparoscopic or robotic PN) is the default approach for most patients. However, there are important factors to consider as possible contraindications for minimally invasive approaches:
- Prior open renal surgery such as open stone surgery, upper tract reconstructive procedures or prior open PN.
- Prior minimally invasive NSS or ablative procedures (laparoscopic or percutaneous).
- Inability to tolerate insufflation due to chronic obstructive pulmonary disease or other conditions.
- Limitations on access or instrumentation due to patient body habitus, although multiple reports describe safe and effective minimally invasive NSS in patients with morbid obesity who may benefit most by avoiding a flank incision.
- Prior extensive intra-abdominal surgery, although a retroperitoneal approach can be utilized in many circumstances as long as the retroperitoneal space can be developed safely.
- Patients with advanced CKD particularly those with complex tumors requiring prolonged renal ischemia time during resection.
The majority of patients with sporadic small renal masses <4 cm in diameter and select patients with tumors <7 cm should be considered for roboticassisted or laparoscopic PN. In patients with solitary kidney (anatomically or functionally) and those with impaired renal function, the surgeon must determine whether a minimally invasive approach will expose the patient’s kidney to undue additional ischemia time that would be minimized by the open surgical approach and use of cold ischemia. While a significant number of methods have been described to cool the kidney during minimally invasive NSS, none have been widely adopted due to the lack of obvious benefit or cumbersome application. The patient may derive greater long-term benefit from an open PN, promoting the preservation of renal function instead of shorter incision length and short-term convalescence advantages. When minimally invasive NSS is considered for endophytic tumors, it is crucial that the surgeon has access to and is proficient in performing laparoscopic ultrasound.
At our institution where the majority of surgeons offer both minimally invasive and open NSS, we review all complex cases and offer a consensus opinion regarding proper approach. If the patient’s initial surgeon does not offer a particular approach, the patient is referred to another surgeon in our group who is capable of offering the approach to the patient.
Selecting approach to laparoscopic and robotic assisted partial nephrectomy
The best approach to minimally invasive NSS depends on patient and tumor characteristics. We have previously published our approach algorithm and herein present a modification based on the flexibility of NSS using the robotic platform. The patient characteristics that most affect surgical approach are prior abdominal surgery and body habitus. In patients with extensive previous intra-abdominal surgery, a retroperitoneal (RP) approach can be used if the tumor is posterior or anterior in the lower or interpolar region.
Upper pole tumors are challenging to access via an RP approach in our experience. An RP approach is contraindicated if the RP space has been violated by previous surgery, such as prior kidney surgery, some vascular procedures, and colectomy. A hand-assisted laparoscopic approach can be considered for patients with extensive intra-abdominal adhesions and tumors involving the upper pole. The hand port incision (usually 6–8 inches in length) can be used for initial lysis of adhesions until additional laparoscopic ports can be placed safely to then complete the remainder of the adhesiolysis laparoscopically. Alternatively, the surgeon can elect to perform the procedure via an open flank incision.
Body habitus can also limit minimally invasive NSS approaches. While there is no established body mass index (BMI) limit in choosing a transperitoneal or RP approach, it is crucial to assess the location and distribution of body fat preoperatively to determine the best approach. Review of the three-dimensional axial imaging is also important to determine the distribution of body fat. A significant amount of cutaneous and RP body fat can make a retroperitoneal laparoscopic approach difficult because of limitations of space and instrument mobility.
For most patients, the proper approach rests with the location of the tumor and its proximity to the renal hilum. Historically, we used a hand-assisted laparoscopic approach to manage upper pole tumors. Our current preference is to use a robotic-assisted approach to manage these tumors to avoid the small yet real risk of port site hernia associated with hand ports (3.5%). In addition, we also prefer to use a robotic-assisted approach for anterior and posterior hilar tumors because of the greater flexibility in dissecting and suturing with the robot. The remainder of the anterior and posterior kidney can be approached via either a robotic-assisted or laparoscopic approach, with posterior tumors accessed retroperitoneally.
Several recent publications have proposed more specific methods to describe the location and complexity of a renal tumor such as the R.E.N.A.L. Nephrometry Score, PADUA classification, and C-Index. This can be used as another variable in the surgical approach selection equation. We currently utilize an algorithm to guide the decision to clamp the renal hilum and suture the renal defect after minimally invasive NSS based on tumor depth of penetration and proximity to the renal sinus. This technique has performed well when compared to R.E.N.A.L. Nephrometry Score in avoiding adverse perioperative outcomes.
Patients referred for a renal mass have often already undergone cross-sectional imaging with CT or MRI. If the patient is diagnosed based on ultrasound or the renal anatomy is not adequately defined on the initial imaging, a renal mass protocol study should be obtained. To minimize blood loss and ischemic damage to adjacent parenchyma, knowledge of the number and location of renal vessels is crucial. There are important distinctions between the arterial and venous blood supply of the kidney that must be kept in mind when performing these operations. All segmental renal arteries are end-arteries with no collateral circulation; therefore, all branches supplying tumor-free parenchyma must be preserved to avoid devitalizing functioning renal tissue. In contrast, intrarenal venous branches communicate among the various renal segments. Ligation of a branch of the renal vein, therefore, will not result in segmental congestion because collateral veins will provide adequate drainage. Tumors in the renal hilum therefore can be accessed by ligating and dividing small, adjacent or overlying venous branches as needed. Major venous branches can then be mobilized completely and retracted freely to expose the tumor with no vascular compromise of uninvolved parenchyma.
In addition, given the low yet real risk of metastasis in patients with tumors <4 cm in diameter (3%), additional preoperative staging studies needed include a chest radiograph, complete blood count, and comprehensive metabolic panel with estimation of GFR. The utility and need of nuclear medicine bone scan and other imaging, such as head CT, depends on the patient’s symptoms or the finding of elevated serum alkaline phosphatase or calcium levels on initial laboratory evaluations.
The basic surgical principles of a PN include:
- Mobilization of the kidney with early vascular control
- Preservation of renal function by limiting hilar clamping
- Complete tumor excision with negative surgical margins
- Watertight closure of the collecting system
- Closure of the renal defect
The retroperitoneal approach avoids entry of the peritoneal cavity which limits morbidity should a postoperative hemorrhage or urine leak develop. In addition, postoperative recovery is often hastened as early return of bowel function is the norm. All approaches to NSS follow similar principles. The only difference between roboticassisted, laparoscopic, and open surgery is the tools used to accomplish the same goals; the goals of the surgery are the same no matter the approach. The surgeon must pick the right set of tools in their hands to accomplish the procedure to the benefit of the patient.
Kidney mobilization and vascular control
After the incision has been made, the retroperitoneal space is entered, the psoas muscle is exposed and the peritoneum is mobilized medially. The kidney is then mobilized outside of Gerota’s fascia, first freeing the upper pole of the kidney, dissecting the medial upper pole from the adrenal gland. The lower pole is then mobilized, identifying the ureter with a vessel loop as needed. The gonadal vein can then be followed cephalad to the renal vein on the left side and inferior vena cava on the right side. Once the renal vein is isolated, further mobilization of the kidney posteriorly is often necessary to identify the renal artery. Alternatively, the renal artery can be identified by freeing the upper pole completely and lifting it laterally. Kidney mobilization should be sufficient to clamp the renal hilum if necessary, resect the renal mass with negative margins, and reconstruct the kidney (Fig. 8.1).
Fig. 8.1. Open partial nephrectomy in a 48-year-old man with a symptomatic 9.2 cm mass. (a) Coronal computed tomography image demonstrates an exophytic right upper pole renal mass. (b) Exposure of the renal mass via an open flank incision. (c) Surgical resection of renal mass with closure of defect over a bolster. No evidence of bleeding after hilar clamp was released. (d) Excised renal mass. Final pathology was classic clear cell renal carcinoma, Fuhrman grade 2/4 with negative margins
Minimally invasive transperitoneal approach
Whether using a conventional, hand-assisted or robotic-assisted laparoscopic approach, we take the same approach for kidney mobilization. For left-sided tumors, the colon is mobilized medially and the lower pole of the kidney is identified. The ureter and gonadal vein are identified, and the lower pole of the kidney is bluntly mobilized off of the psoas muscle, and the lower pole of the kidney and ureters are lifted anteriorly. For the robotic-assisted approach, the third robotic arm is useful at this point to maintain anterior elevation of the kidney. For the hand-assisted and conventional laparoscopic approaches, a laparoscopic kitner or suction/irrigator device through an assistant port provides lift. The medial dissection is carried cephalad following the gonadal vein to identify the renal vein. If exposure is not ideal, the upper pole of the kidney can be mobilized, further releasing attachments of the pancreas, spleen, and colon. In general, even if we do not intend to clamp the hilum, we isolate the renal vein and artery to be able to clamp the hilum en bloc, artery only, or artery and vein separately. For hilar tumors, further dissection of more distal branches of the artery and vein can be carried out to allow for clamping of segmental branches or ligation of individual vessels entering the tumor (Fig. 8.2).
For right-sided tumors, we begin the dissection by incising the peritoneum over the right kidney and mobilizing to medially until the duodenum is identified. The duodenum is then Kocherized and further dissection is carried cephalad so that the peritoneum between the upper pole of the kidney and liver is incised. From that point, the dissection progresses as described for the left-sided procedure.
Fig. 8.2. Robotic-assisted partial nephrectomy in a 59-yearold woman with biopsy-proven renal cell carcinoma. (a) Computed tomography image demonstrates an endophytic left lower pole renal mass. (b) Postoperative CT demonstrating good perfusion and complete excision. (c) Exposed renal hilum. (d) Tumor exposed. (e) Resection bed. (f) Repaired defect using nitrocellulose bolster. (g) Closure of Gerota’s fascia over defect using clips. (h) Resected tumor ready for removal. Final pathology was clear cell renal carcinoma, Fuhrman grade 3/4 with negative margins
Further dissection depends on the location of the tumor. For upper pole tumors it is often necessary to mobilize the entire kidney so that the upper pole can be lifted anteriorly. The surgeon must judge whether this mobilization is best performed with Gerota’s fascia intact or within Gerota’s.
The assistant role in aiding exposure is critical in both the laparoscopic and robotic-assisted approaches. One advantage of the robotic approach is that once the lower pole and ureter are mobilized and elevated by the third arm, the console surgeon is less reliant on retraction from the bedside assistant.
Minimally invasive retroperitoneal approach
As initial access to the kidney is posterior and interpolar in this approach, the renal hilum is mobilized and isolated first. The hilum is typically in line with the port placed at the costovertebral angle. If the thoracolumbar fascia has not been incised when obtaining access, the hilum may be obscured. It is useful to identify the ureter, gonadal vein, and psoas muscle to maintain proper orientation. For most cases, the renal artery is encountered first when dissecting the renal hilum. The vein, which is usually behind the artery in this approach, can also be isolated if the surgeon intends to clamp it as well.
High quality preoperative cross-sectional imaging is crucial as a guide to tumor location. For open PN, the tumor may be identified and isolated early in the dissection if mobilization is performed within Gerota’s fascia. However, for minimally invasive approaches, Gerota’s is entered and the tumor is isolated after mobilization of the hilum so that the perinephric fat will not obscure the hilum during dissection. We enter Gerota’s fascia at a point away from the tumor and identify the capsule of the normal kidney first. Ideally, Gerota’s is mobilized in such a way that flaps of perinephric fat remain intact to reapproximate over the site of resection at the conclusion of the case. The fat covering the tumor is left in place to send with the specimen to pathology, but it is important to expose the kidney capsule circumferentially around the tumor in preparation for the renorrhaphy after the tumor is excised.
Several reports have established intraoperative ultrasonography (US) as a useful adjunct when performing PN. Intraoperative US is particularly useful for patients with intrarenal tumors that are not visible or palpable even after the perinephric fat has been removed. The topographical information obtained from intraoperative US is also useful in patients with tumors that extend deep into the kidney. In such instances US is useful for defining the appropriate margins of resection and for allowing preservation of as much uninvolved parenchyma as possible while still obtaining negative surgical margins. Ultrasound is also useful for locating multicentric tumors, venous extension, and the presence of other renal lesions. Advances in laparoscopic US have greatly aided the management of increasingly complex tumors through a minimally invasive approach. We advocate its use on every NSS to provide “real time” information about tumor dimensions to assist in surgical dissection and to improve the surgeon’s US skill for assessing and managing more complex tumors. The incorporation of ultrasound for robotic NSS has been greatly aided by TilePro, which allows the console surgeon to visualize the operative field and US image at the same time.
Prevention of ischemic injury
A number of steps can be taken to minimize ischemic injury during PN. Some of these options are available to both the open and minimally invasive surgeon and depend largely on the depth of the tumor, proximity to the renal sinus, location of the tumor in the kidney and its blood supply.
Depth of tumor
For laparoscopic and robotic-assisted procedures, we have created an algorithm to determine when it is advisable to clamp the renal hilum. If the tumor has less than 5 mm of penetration into the kidney and is greater than 5 mm from the renal sinus, it is often unnecessary to clamp the hilum, although the hilum should still be isolated in the event that the need to clamp arises during dissection. It is important to confirm the superficial nature of the tumor with intraoperative ultrasound. Hemostasis can frequently be achieved with a combination of argon beam coagulation and hemostatic agents. For those tumors with
>5 mm but <10 mm of penetration into the parenchyma, we typically clamp the hilum but unclamp once adequate hemostasis of the base of the resection has been obtained, either with a running absorbable suture or application of hemostatic agents. This is often referred to as “early unclamping” in the recent literature; however, this technique has been practiced for some time and can be used in any approach.
Proximity to sinus
For those tumors within 5 mm of the renal sinus/ hilum, the hilum should be clamped. Again, if the base of the tumor can be controlled with a running absorbable suture, early hilar unclamping can minimize ischemia time. Early unclamping is not recommended for large, central tumors where large segmental vessel can result in significant blood loss or result in the need for complex reconstruction. In this scenario, the use of cold ischemia may be more appropriate.
Segmental artery clamping can be used in any approach. When the tumor is supplied by a distinct artery, ligation of this artery can provide hemostasis without ischemia to the remainder of the kidney. Not clamping the renal vein also helps to minimize ischemic injury.
If the anticipated renal hilum clamp time exceeds 20 min, additional protection from ischemic renal injury is necessary. Local hypothermia currently offers the most effective means for this. Ice slush packed around the kidney is a common method for renal cooling. A wide variety of alternative approaches have been presented without obvious advantage over ice slush. To date, there is no compelling evidence that cold ischemia offers a significant advantage over warm ischemia as long as hilar clamp time is minimized. A recent multi-institutional study of 660 patients with solitary kidneys undergoing PN demonstrated no significant difference in long-term renal function between warm and cold ischemia. The most critical determinants of renal function were the quality and quantity of the renal remnant. Cold ischemia allows up to 40–60 min of clamp time without permanent kidney damage. It is important to cover the entire kidney with ice for at least 5–10 min immediately after occluding the renal artery before beginning the PN. This allows the kidney core temperature to reach 15–20°C, optimizing renal preservation. Administration of intravenous mannitol (12.5 g) 15–30 min before clamping the renal artery induces diereses, reduces renal tubule swelling and protects against ischemic renal damage. Careful attention to perioperative fluid status is crucial, particularly for patients with a solitary kidney.
Other considerations related to ischemia
We have found that it is valuable in all cases to be prepared prior to tumor resection to clamp the renal hilum and suture the base of resection. There is considerable literature touting the resection of renal masses without hilar clamping for minimally invasive approaches. The most commonly reported technique is to utilize a radiofrequency energy device such as the Habib. While this has been demonstrated to be effective, our concern is that the tissue char created by the device makes visualizing the resection margin difficult, destroys surrounding benign parenchyma, and can result in delayed bleeding or urine leak. Other techniques described to limit ischemia include pre-placement of hemostatic sutures under the tumor with ultrasound guidance and relative hypotension. While reducing kidney ischemia is important, this must be balanced with sound oncologic principles. We believe that cold resection in a bloodless field achieved with renal artery clamping best achieves this.
A second related issue is the decision to clamp the renal artery alone, both the artery and vein, or segmental arteries alone. The literature suggests that clamping the artery alone is safe and likely limits renal damage. However, if the tumor is deep and/or central in location, it is often helpful to clamp the renal artery and vein to achieve the best visualization. The choice of clamp (bulldog or Satinsky) depends on the anatomy of the renal hilum and patient. Every effort should be made to isolate the renal artery separately from the renal vein, but in the case of a complex hilum with multiple renal vessels, using a Satinsky clamp across the entire hilum is often safer and more expedient. For minimally invasive approaches, laparoscopic bulldog or Satinsky clamps are available. Extra care must be taken when using a laparoscopic Satinsky clamp with a robotic approach as the robotic arms can clash with the clamp externally and cause major vascular injury. Segmental clamping with a bulldog clamp is appropriate when there is clearly a discrete artery branch supplying the tumor.
Preoperative imaging can aid in defining the renal vasculature, but the ultimate decision on how to proceed with hilar clamping is made intraoperatively once the hilum and tumor have been exposed. Caution should be exercised in segmental clamping of posterior polar tumors as these tumors are often supplied by both the polar artery and the posterior branch. It is important to prepare the hilum to clamp the main renal artery and vein even when segmental clamping is employed in the event that vascular control is insufficient, and the main artery and/or vein need to be clamped during tumor excision.
Excision of the tumor with a conservative margin (2–3 mm) of normal parenchyma is the preferred technique for PN. This can best be accomplished by wedge resection for centrally or peripherally located tumors, or by transverse heminephrectomy for large polar tumors. Frozen sections of the base of resection to confirm negative surgical margins can be obtained if needed. The perinephric fat overlying the tumor should be left undisturbed to ensure en bloc removal of the malignancy. Patients with multifocal disease can be managed by PN if possible, but they are at increased risk for local recurrence after NSS. Regardless of the approach used, cold excision allows for optimal visualization to discern malignant from benign renal tissue.
Renal masses are often completely enveloped by a pseudocapsule of fibrous tissue that can allow relatively avascular tumor removal by enucleation. The technique of enucleation involves circumferentially incising of the parenchyma around the tumor, identifying the plane between the pseudocapsule and adjacent uninvolved parenchyma, and then gently mobilizing the lesion with a blunt instrument. During enucleation of peripheral tumors, it is generally unnecessary to occlude the renal artery, and the few transected blood vessels at the base of the enucleation can simply be ligated with suture. The argon beam coagulator can be used to treat the resection base, fat or oxycel can be placed into the cavity, and the resection edges can be sutured together to further assure hemostasis.
While enucleation has typically been reserved for patients with a peripheral, well-encapsulated tumor or hereditary renal cancer syndromes, growing data suggests that oncologic outcomes of enucleation are similar to wedge resection. A retrospective cohort study of 982 patients undergoing standard PN and 537 patients undergoing enucleation showed no significant difference in progression-free or cancer-specific survival after adjusting for other meaningful variables. The advantage of enucleation is maximal preservation of renal function and improved hemostasis without apparent loss of oncologic efficacy. Ultimately, the surgeon must judge whether enucleation is appropriate on a case-by-case basis.
Obtaining early vascular control and occluding the renal artery when necessary are essential maneuvers to minimize intraoperative blood loss during NSS. Temporary occlusion of both the renal artery and vein also provides improved operative visualization which can be invaluable during challenging cases. The renal vein clamp is removed first and the parenchyma is carefully inspected during deep forced inspiration to identify additional bleeding sites that are not otherwise apparent. For minimally invasive procedures, decreasing the insufflation pressure to 5 mm Hg at the end of the procedure helps to determine it adequate hemostasis has been achieved.
When excising the tumor during an open surgical approach, vessels can be suture ligated or clipped when they are encountered as they can retract into the parenchyma and become more difficult to control after the tumor is removed. Larger vessels tend to be located medially within or near the renal sinus. Residual bleeding vessels should be ligated with absorbable suture once the tumor is excised. The use of Argon beam coagulator, fibrin glue, and other hemostatic agents is also helpful for obtaining hemostasis. Reapproximation of the capsule with absorbable suture tied over a nitrocellulose bolster or perinephric fat aides in hemostasis, but this should not be done until the parenchymal bleeding has been adequately controlled. Other energy sources, such as radiofrequency devices or laser, have been described to aid in hemostasis.
For minimally invasive approaches, we have found that using a running suture at the base of the resection (2–0 absorbable suture) can improve hemostasis and does not add significantly to the warm ischemia time. However, larger transected veins or arteries should be individually controlled with absorbable suture first. Better visualization in the case of venous bleeding can be achieved by increasing the insufflation pressure to 20 mm Hg for short periods of time without detrimental effects on renal function.
For tumors within 5 mm of the renal sinus or collecting system, our preference is to resect the tumor with cold scissors while the hilum is clamped, close the renal sinus or collecting system with an absorbable suture, re-approximate the base of the resection bed with an absorbable suture, and then unclamp the kidney. Following that, a bolster composed of rolled nitrocellulose sheets with pre-attached 0-vicryl sutures on CT-1 needles is placed and secured in on position using Hem-O-Lok clips using a sliding renorrhaphy technique. Additional sutures of 0-vicryl on CT 1 needles with a Hem-O-Lok pre-tied in place at the end can be used to further secure the bolster in place after tightening the suture with a second Hem-O-Lok clip.
Closure of the collecting system
Watertight closure of the collecting system is essential to prevent urinary fistula formation. Surgeons should look for entries into the collecting system centrally as the renal tumor is excised. If possible, the collecting system should be closed with absorbable suture before it has been completely transected. Calices and infundibula are often more difficult to locate if they have been allowed to retract into the parenchyma or perisinus fat. For minimally invasive approaches, entries into the collecting system can be closed with a running absorbable suture which can be secured using Lapry-Ty clips to save ischemia time.
The perspective regarding ureteral stenting at the time of PN has evolved as experience with NSS has accumulated. Initially, stents were placed whenever a significant opening in the collecting system was identified, regardless of the location of the defect or the complexity of the reconstruction. More recently, stents are placed only when major reconstruction of the collecting system is required. With any entry into the collecting system, a drain should be placed at the conclusion of the case.
Outcomes of nephron-sparing surgery for renal cell carcinoma
Perhaps the best way to judge the various approaches for extirpative management of small renal masses is to directly compare their outcomes. More robust, long-term data exit for open PN than for the laparoscopic or roboticassisted approaches. In addition, there is also appropriate selection bias among the approaches making direct comparison difficult. The focus of the following literature review is on contemporary series. While we report the mean results here, they are not weighted by the number of patients in the individual study included, and therefore may not be representative of all patients undergoing the various approaches. The table references are included in the reference section.
Table 8.1 summarizes general demographic information and perioperative outcomes of patients undergoing NSS. Patient age was similar across all series with a larger percentage of patients with solitary kidneys treated with an open surgical approach. Only a small number series report results for the retroperitoneal laparoscopic or robotic approaches. We did not include data for the hand-assisted approach because of the small number of cases reported in the literature.
Mean tumor size was larger on average for the open surgical approach. The shortest operative times were reported for the retroperitoneoscopic approach, reflecting the direct access to the renal hilum and tumor with this approach and the advantage of avoiding an open flank incision. On average, though, the open surgical approach took less time than robotic or laparoscopic transperitoneal approaches. There was variable reporting of hilar clamp time, with the shortest ischemia times reported for the robotic-assisted approach. Hospital stays were shortest for the laparoscopic and robotic-assisted approaches; however, this is based on only a few series for the retroperitoneoscopic approach and may not reflect the true advantage of the retroperitoneoscopic PN in terms of convalescence and recovery. We recently reported our experience with robotic-assisted retroperitoneal PN with a mean length of hospital stay of 1 day. Estimated blood loss was consistently less for minimally invasive than the open approach.
Table 8.2 summarizes the complications of NSS by approach. The literature is plagued by a lack of standardization in defining and reporting complications. However, recent literature has adopted more standardized complication reporting methods, such as the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) or the more surgically oriented Clavien Classification. The emphasis in this section will be the diagnosis, management, and clinical significance of the more common complications of NSS.
Table 8.1. Demographic and perioperative outcomes by surgical approach
Urinary fistula formation
Urinary fistula formation is the most commonly reported complication of NSS. The mean rate for most series we reviewed is 3–4%, with fewer patients experiencing urine leak with the open approach. There is significant variability in urine fistula rates for the laparoscopic and roboticassisted approaches. This possibly reflects the early experience of surgeons with these approaches and the more frequent use of energy sources to perform the tumor resection, potentially obscuring the renal anatomy. Urinary fistula is defined as persistent (>7 days) drainage of fluid (>50 cm3/day) with a drainage fluid to serum creatinine ratio of greater than 2 mg/dl.
Risk factors for urinary fistula formation in both the open and minimally invasive approaches include large tumor size (>4.0 cm), the need for extensive reconstruction of the collecting system and central tumor location. Urine fistulas often resolve spontaneously with conservative management. If urine fistulas persist, endoscopic manipulation, including retrograde pyelography and placement of a temporary ureteral stent to encourage the flow of urine down the ureter, may be necessary. The surgical drain is left in place until the fistula resolves, and the drain fluid creatinine level should be reassessed before removing the drain. If a normal pyelocalyceal system is identified on retrograde pyelogram yet drain output persists, a renal papilla that was excluded from the remaining collecting system during the rhenorraphy is the likely source. In this circumstance, it may take several months until that papilla no longer functions and the urine leak resolves. Alternatively, variable success has been reported with ureteroscopic division of suture obstructing infundibula using the holmium laser.
Acute kidney injury
Acute renal failure (ARF) requiring renal replacement therapy is the second most common complication of NSS. The low rates of this complication reported for minimally invasive approaches suggest either under-reporting or that tumors managed by these approaches are consistently less complex than those managed with the open approach. Ischemic renal injury from hilar clamping and reduced parenchymal mass after PN are the primary causes of ARF. Perinephric urinoma and vascular thrombosis can also lead to ARF after NSS. The most significant predisposing factor for the development of ARF in this series was the presence of a solitary kidney. Novick et al. found that ARF only occurred in 2% patients with a normal contralateral kidney. In contrast, ARF developed in 26% of patients with a solitary kidney. In the solitary kidney cohort, additional risk factors for ARF included large tumor size (>7 cm), greater than 50% parenchymal excision, and greater than 60 min of cold ischemia time. ARF rates after elective PN should be relatively low as these patients have normal contralateral kidneys which can maintain perioperative renal function. The management of ARF after NSS should include careful attention to volume status, appropriate adjustment of medication doses, and dialysis as needed. More recently, the same group evaluated factors that determine renal function after PN in solitary kidneys. In multivariable analyses, increasing age, larger tumor size, lower preoperative GFR, and longer ischemia time were associated with decreased postoperative GFR (p < 0.05). On multivariable analysis, the percentage of renal parenchyma spared and the preoperative GFR proved to be the primary determinants of ultimate renal function, and time of intraoperative renal ischemia lost statistical significance. Long-term renal function after PN was determined primarily by the quantity and quality of renal parenchyma preserved. It is important to emphasize that these results were obtained in a series notable for short warm ischemic times and liberal use of hypothermia and will likely not apply to cases with longer warm ischemia. Indeed, when this was evaluated in a more homogenous group of patients with solitary kidneys managed only with warm ischemia, the ischemic interval proved to be a significant predictor of ARF, and when extended beyond 25 min, it served as an independent predictor of new onset severe CKD.
Table 8.2. Complications by surgical approach
Other complications of NSS include postoperative hemorrhage, perinephric abscess formation, and renal vessel thrombosis. Hemorrhage is more frequently reported in laparoscopic series and occurs at a similar rate in open and roboticassisted series (Table 8.2). Most studies defined hemorrhage as intraoperative bleeding requiring resuscitation. Pseudoaneurysm or arteriovenous fistula form when suture thrown in the base of the tumor resection bed fuses arteries and veins, resulting in direct communication between the two. This is more frequently reported in open surgical series, likely reflecting the greater complexity of these tumors. Delayed postoperative bleeding with perinephric hematoma can present with pain, gross hematuria, hypotension, flank mass, or bruising, and occurs more frequently with the open than minimally invasive approaches. After initial resuscitation and stabilization of the patient, a CT scan of the abdomen and pelvis is useful in making the diagnosis. Delayed bleeding can frequently be treated in interventional radiology with selective renal artery angiography and coil embolization. Avoiding deep passes with large needles into the renal sinus intraoperatively diminishes the risk of this complication.
Although complications of NSS are not uncommon, most can be managed conservatively and associated morbidity is often minimal. The rate of major complications (Clavien 3 or higher) is approximately 5% for most approaches. For the conventional laparoscopic approach, the rate is 11%, potentially reflecting its inherent technical challenges, especially early in a surgeon’s experience. Table 8.2 also summarizes complications by system. Complication rates in most series are likely under-reported. Standardized reporting of complications and meticulous patient followup is essential to better compare the approaches for NSS. Mortality rates after NSS compare favorably with those for RN (1–2%).Taken together; these results suggest that NSS can be performed safely and with minimal morbidity. Of course, individual outcomes depend greatly on surgeon experience and tumor complexity.
The rate of conversion to open PN is similar for the different minimally invasive approaches.
Table 8.3. Oncologic and renal function outcomes
Conversion to nephrectomy was reported more commonly with robotic-assisted NSS, reflecting the early experience with this approach and issues with patient and tumor selection.
Functional and oncologic outcomes following nephron-sparing surgery
Preservation of renal function
Table 8.3 summarizes the renal function and oncologic outcomes of NSS by approach. A fundamental issue with such a comparison is the lack of standardized methods or timeframe for reporting renal function, as well as the absence of this data in many series. Several series report the change in creatinine from baseline, but newer series more often report the change in GFR which better assess the level of CKD and the need for renal replacement therapy. Most approaches demonstrate similar renal function outcomes. It must be kept in mind, though, that most open series represent larger, more complex tumors. The use of R.E.N.A.L. Nephrometry Score may allow future series to compare results in patients with similar tumor size and complexity.
Novick et al. reported on the long-term renal function in 14 patients with solitary kidneys who underwent PN for localized tumors with no preoperative clinical or histopathologic evidence of primary renal disease. Postoperative renal function remained stable in 12 patients, whereas two developed end-stage renal failure. Nine patients developed proteinuria: low grade in four (<750 mg/24 h) and moderate to severe in five (930–6,740 mg/24 h). A statistically significant inverse association was found between the degree of proteinuria and amount of residual renal tissue. Renal biopsy performed in four patients with moderate to severe proteinuria showed focal segmental or global glomerulosclerosis.
These data suggest that patients with solitary kidneys with more than a 50% reduction in renal mass after PN are at increased risk for developing a hyperfiltration injury, manifested by proteinuria, glomerulopathy, and progressive azotemia. The development of significant proteinuria usually preceded detectable renal deterioration. These observations suggest that patients with solitary kidneys who undergo PN should be followed with serial 24-h urinary protein evaluations in addition to serum creatinine levels and calculated GFR. A low-protein diet should be instituted in patients who develop proteinuria of >150 mg/24 h, and treatment with angiotensin-converting enzyme inhibitors should be considered.
As there is less robust, long-term data with some of the newer minimally invasive approaches, surgical margin status is often used to assess oncologic efficacy. Recent reports, though, suggest that focal positive margins have minimal adverse oncologic impact following PN. Positive margin rates for most approaches are reported to be 2–3%. However, there is considerable variability in this rate, suggesting the impact of surgeon experience. The rates of local recurrence, another short-term oncologic endpoint, are consistently low regardless of the approach, further strengthening the argument that focal positive margins likely have minimal oncologic impact.
A recent report of a randomized controlled trial of radical versus NSS demonstrated a 10-year overall survival of 81.1% for RN and 75.7% for PN, with a statistically significant difference in favor of RN (p = 0.03). When the authors limited the analysis to patients with RCC only, there was no significant difference found between these approaches. The fundamental limitation of this multicenter randomized-controlled study was poor accrual which limits its power to detect a difference between the approaches. Another major issue was the less than expected number of events seen in the study, with only 12/117 patients dying from RCC and 21 patients developing disease progression after a median follow-up of 9.3 years.
Several recent reports have documented longterm disease-specific survival rates for most of the surgical approaches to NSS. Ten-year diseasespecific survival for open PN ranges from 77% to 100% in the series reporting this endpoint. While this data is not available for the robotic-assisted approaches as of yet, a 5-year disease-specific survival of 97.6% has been reported for the conventional laparoscopic approach, suggesting that in well-selected patients, it can offer comparable cancer control to the open approach (Table 8.3). Reviewing the outcome of NSS in 216 patients with sporadic RCC treated at the Cleveland Clinic Foundation, disease-specific survival was associated with pathologic stage, tumor size, multiplicity, unilaterality, and whether the tumor was discovered incidentally or on the basis of clinical symptoms. Another study reported the outcome of NSS in 241 patients. The mean diseasespecific survival rate was 95% at 3 years, and there were only two cases of local tumor recurrence. The development of renal failure after PN also has a significant impact on quality of life and mortality. The 1-, 2-, and 5-year survival rates for patients aged 55–64 years while on dialysis following RN for RCC in a solitary kidney are 84%, 67%, and 33%, respectively, and fall to 73%, 51%, and 16% in patients older than 64 years. Currently, these patients have to survive disease free on dialysis for 12–24 months before renal transplantation is considered.
Patterns of tumor recurrence and guidelines for follow-up after NSS
The surveillance schedule after NSS for RCC receives relatively little attention in the literature. There is a higher risk of local tumor recurrence after NSS compared to RN, with larger studies suggesting an incidence of up to 10%. Data concerning the occurrence of metastatic disease after NSS for RCC has also been lacking, although it is presumed that rates are not markedly different from those observed after RN. The incidence of both local and metastatic tumor recurrences after NSS for RCC varies according to the pathologic tumor stage. In designing an appropriate strategy for postoperative surveillance after NSS for RCC, a balance must be established between detecting recurrent disease early and overly aggressive follow-up. The cost of postoperative monitoring studies is an additional issue. The available data indicates that surveillance after NSS can be tailored according to the pathologic tumor stage and can perhaps be more limited than the current practice in many centers.
The recommended postoperative surveillance scheme after NSS for sporadic localized RCC is as follows: all patients should be evaluated with a medical history, physical examination and selected blood studies, including serum calcium, alkaline phosphatase, liver function tests, blood urea nitrogen, serum creatinine, and electrolytes on a yearly basis. A 24-h urinary protein measurement should also be obtained in patients with a solitary remnant kidney to screen for hyperfiltration nephropathy . The need for postoperative radiographic surveillance studies varies by stage. A yearly chest X-ray is recommended after NSS for all stages since the lung is the most common site of postoperative metastasis. We recommend obtaining abdominal CT scans based on modified risk criteria. (Table 8.4).
Table 8.4. Surveillance regimen after partial nephrectomy for localized RCC
Despite the clinical research supporting NSS for the treatment of small renal masses, this procedure remains underutilized. Further education and awareness of treatment outcomes associated with NSS is essential. Whether an open or minimally invasive technique is used, it is important for surgeons to have a firm grasp on the concepts unique to NSS, including kidney mobilization, techniques for clamping the renal hilum, and management of postoperative complications, such as bleeding, infection, and urinary fistula. It is now clear that, despite the technical challenges associated with NSS, excellent oncologic control and preservation of renal function make PN the preferred approach for the treatment of small renal masses. All patients with tumors <7 cm in greatest diameter should be considered for a nephron-sparing procedure whenever possible. Only once this is decided should the surgeon select the appropriate surgical approach: open or minimally invasive.