Contemporary Experience with Laparoscopic Partial Nephrectomy

Abstract

Introduction:

We evaluated our contemporary outcomes with laparoscopic partial nephrectomy (LPN) for renal cortical neoplasms (RCN) by an experienced single surgeon in our last 100 consecutive patients.

Methods:

We reviewed a prospectively established database and identified 378 patients who underwent LPN for RCN. Data from the most recent 100 consecutive patients (June 2007 to August 2009) were evaluated for oncologic, functional, and recovery outcomes, and tumors were stratified by size. There were 57 men and 43 women. The mean tumor size was 2.8 cm (range 0.9–9.0 cm).

Results:

The mean operative time was 132 minutes (range 95–350 minutes) and the mean blood loss was 175 mL (range 25–1000 mL). There were 13 (13%) complications. Seventy-seven tumors were ≤4 cm (group 1) and 23 tumors were >4 cm (group 2). The groups were similar in terms of demographics, perioperative data, and complications. The mean warm ischemia time in groups 1 and 2 were 25.9 and 29.5 minutes, respectively (P=.04). Overall, 79% of the tumors were malignant renal cell carcinoma variants with a positive margin rate of 2%. With a median follow-up of 8 months, there was 1 local recurrence. The median change between preoperative estimated glomerular filtration rate and 3 months' follow-up estimated glomerular filtration rate was 10.1 mL per minute per 1.73 m² (P>.001).

Conclusions:

LPN is a safe and effective treatment option for RCN. With extensive experience and a well-developed surgical technique, patient outcomes are improved and postoperative complications are reduced. LPN may be applied to more complex cases including larger and hilar tumors.

Introduction

The incidental detection of renal masses has increased over the last two decades. Renal cell carcinoma (RCC) represents 2% of all adult cancers with rates rising over the last three decades with an average increase of 2% to 3% per year.¹ Radical nephrectomy (RN) and partial nephrectomy (PN) have been the standard of care for the treatment of renal cortical neoplasms (RCN). For properly selected tumors, PN has shown comparable results to RN in terms of both functional and oncologic outcomes.^2–5 With the evolution of minimally invasive nephron sparing techniques such as laparoscopy, robotic-assisted laparoscopy, and ablative technologies, the treatment of RCN has changed dramatically. Despite the steep learning curve associated with laparoscopic partial nephrectomy (LPN), it is the minimally invasive standard for extirpation of small renal masses. With improvement of surgical technique, LPN has been applied to select patients with larger renal masses (4–7 cm) and tumors with an endophytic or hilar location.^6,7 In addition, short-term patient-related benefits for LPN include a reduction in perioperative morbidity, shorter hospital stay, and faster overall recovery.⁷ This cohort represents outcomes from the most recent 100 LPNs at a single institution with a surgical team that has extensive experience in laparoscopic renal surgery, including a high volume of LPN, and emphasizes modifications in technical aspects of the procedure.

Materials and Methods

We retrospectively reviewed our IRB-approved, prospective, minimally invasive database. Overall, 378 LPN cases performed by a single surgeon with an experienced operative team were identified. We evaluated the most recent (July 2007–August 2009) 100 consecutive patients undergoing LPN to document contemporary results with the procedure. All patients underwent preoperative counseling regarding their treatment options (surgical and nonsurgical). The final decision as to treatment strategy for patients with RCN was a consensus reached between the surgeon and patient.

There were 57 men (57%) and 43 women (43%) with the mean age of 55.6 (range 25 to 80). Four (4%) patients were identified with a solitary kidney. The mean tumor size was 2.8 cm (range 0.9–9.0 cm). There were 42 (42%) upper pole, 16 (16%) interpolar, 28 (28%) lower pole, and 14 (14%) hilar tumors (within 5 mm of the main renal artery or vein). Table 1 lists patient demographics, preoperative data, and tumor characteristics.

Table 1.

Demographics and Preoperative Tumor Characteristics

Patients	100
Mean age (range)	55.5 (25–80)
Men	57
Women	43
Median BMI (kg/m²) (range)	27 (17–50)
Tumor in solitary kidney	4
Left	56
Right	44
Solid tumor	60
Cystic tumor	27
Solid and cystic tumor	13
Mean tumor size (cm) (range)	2.8 (0.9–9.0)

BMI, body mass index.

Patient demographics, tumor characteristics, intraoperative, and perioperative data were evaluated. All patients underwent a full staging evaluation with computed tomography (CT) or magnetic resonance imaging of abdomen and pelvis, chest X-ray, and liver function tests. Renal tumors were classified preoperatively as exophytic, mesophytic, or endophytic based on cross sectional imaging.⁸ Exophytic tumors were defined as those in which the lesion extended >60% off the natural surface of the kidney, endophytic tumors were defined as <40% of the lesion extending off the kidney surface, and mesophytic tumors were those lesions extending 40% to 60% off the surface of the natural border of the kidney. Preoperative, immediate postoperative, and follow-up serum creatinine levels were measured and collected to assess renal functional outcomes. Estimated glomerular filtration rate (eGFR) was calculated according to the Modification of Diet in Renal Disease equation, and expressed as mL/min/1.73 m.^2,9

We defined a urine leak as postoperative drainage persisting after the second postoperative day with fluid biochemistry compatible with urine. Our follow-up protocol consists of regular imaging at 3 months postoperatively with annual imaging thereafter. Treatment failure was defined as a positive margin at the time of surgery or enhancement of the tumor bed following resection. Follow-up laboratory was obtained at each evaluation and consisted of electrolytes, serum creatinine, liver function tests, and blood count.

Surgical technique

The decision to use a transperitoneal or retroperitoneal approach was based on tumor location and history of prior abdominal surgery. An intraoperative laparoscopic ultrasonography is used to perform a complete and systematic evaluation of the kidney in every case. Tumor location, depth of tumor invasion into the renal parenchyma, and tumor vascularity are documented prior to resection. We routinely use the continuous flow-monitoring (CFM) feature to evaluate the entire kidney before and after temporary occlusion of the renal artery to confirm adequate vascular control before clamping and resection. If there is persistence in flow after clamping, then a more extensive hilar dissection is performed to determine if a second renal artery exists. After the administration of mannitol (12.5 g), two laparoscopic bulldog clamps (Aesculap, B. Braun Medical, Bethlehem, Pa) are applied to the renal artery. Renal vein clamping is only performed with resection of hilar tumors due to the increase in potential bleeding. All tumors are excised with cold laparoscopic scissors with hemostatic control and closure of the collecting system defects performed using 2–0 vicryl sutures with intracorporeal suturing. Additional hemostasis included use of a wet monopolar radiofrequency dissector (Floating Ball, TissueLink^™). Parenchymal closure over an absorbable surgicel bolster (Surgicel^® wrapped over Gelfoam^®) (Ethicon, Inc.), and a thrombin-based product (FloSeal- Baxter Healthcare) is then performed with horizontal mattress sutures anchored on both ends with LapraTy clips (Ethicon Endosurgery). After reconstruction and unclamping, the excised tissue is sectioned to evaluate the margin and frozen section analysis is performed to examine margin status.

Statistical analysis

Statistical analysis was performed using the SPSS v.17 (SPSS) software. All P values were two-sided, and P<.05 was considered statistically significant. The categorical variables were compared using a Chi-square test or Fisher's exact test, as appropriate. We performed a univariate and multivariate analysis on factors contributing to a postoperative decrease in eGFR. Factors evaluated included age, race, gender, tumor size, estimated blood loss, length of hospital stay, body mass index, presence of hypertension, diabetes, or coronary artery disease, and ischemia time.

Results

There was an 80% malignancy rate with 79% being RCC variants. Final histology demonstrated clear cell in 53 patients, papillary (Type I) in 16 patients, chromophobe in 8 patients, and collecting duct carcinoma in 2 cases. Lymphoma was diagnosed in one patient. Benign lesions were identified in 20 cases with angiomyolipoma in 8 cases, oncocytoma in 4, and complex cysts without evidence of malignant cells in 8 cases (Table 2). Two patients demonstrated a positive margin on final pathology. The first patient presented with a T1a endophytic mass and demonstrated a high-grade clear cell RCC with a focal positive margin in the resection bed. Recent follow-up CT imaging has not demonstrated recurrence and the patient's serum creatinine remains unchanged from preoperative values. The second patient presented with a 1.6×1.9 cm solid enhancing exophytic renal mass found to be a low-grade conventional RCC on final pathology. After 2 years of follow-up with annual CT scans, no signs of local recurrence have been found.

Table 2.

Intraoperative Data and Histology

Patients	100
Surgical approach
Transperitoneal	83
Retroperitoneal	17
Median warm ischemia time (min) (range)	26.6 (11–45)
Median EBL (mL) (range)	175 (25–1000)
OR time (min) (range)	132 (95–350)
Conversions	5
Blood transfusion	8
Complications	13
Mean length of stay (days) (range)	2 (1–14)
Positive margin	2
Benign lesions	20
Complex cysts	8
AML	8
Oncocytoma	4
Malignant lesions	80
Clear cell	53
Chromophobe	8
Papillary	16
Other	1
Local recurrences	1

In our series the transperitoneal approach was used in 83 (83%) patients (50 left-sided and 33 right-sided). The mean operative time was 132 minutes (range 95–350). The mean warm ischemia time was 26.6 minutes (range 11–45) and the mean estimated blood loss was 175 mL (Table 2). All but two procedures were completed laparoscopically. In the first case, bleeding necessitated conversion to open PN (OPN), whereas in the second case the surgeon elected to convert to OPN due to significant intraoperative failure to progress from severe peri-nephric adhesions. Three cases (3%) were converted to laparoscopic RN. In two of these three cases, the surgeon elected to proceed to laparoscopic RN due to positive margins and the tumor's proximity to the surgical margin in the frozen section, respectively. In both of these cases the complex nature of the PN had been discussed with the patient who was aware of the significant risk of RN. The third case was converted to laparoscopic RN after the intraoperative ultrasonography evaluation revealed that the mass had grown in size, and was measured at 4.3×3.6 cm. The patient initially presented with an endophytic 2.9×2.9 cm cystic mass with enhancing solid components on CT scan. A PN was attempted; however, the renal vein impeded our ability to obtain a negative margin. Frozen section demonstrated a positive margin (low-grade clear cell RCC), which led to the decision to proceed to RN.

Overall, 13 (13%) perioperative and postoperative complications were recorded in the cohort. Hemorrhage was the most common complication with a total of 8 (8%) of patients requiring transfusion (3 intraoperative and 5 postoperative hemorrhage). Of the five postoperative hemorrhages, one patient required embolization to achieve hemostasis, whereas the other four patients were managed conservatively. Additionally, 1 patient had atelectasis with a pleural effusion requiring drainage, 1 patient had a pneumothorax treated with insertion of a chest tube, and 3 patients had a urine leak, which resolved with drained after endoscopic placement of an indwelling stent.

The mean preoperative, postoperative, and 3-month follow-up eGFR were 78.3 (SD=22.1), 71.6 (SD=20.7), and 68.2 (SD=17.6) mL per minute per 1.73 m², respectively. The mean change between preoperative and postoperative eGFR was 6.7 mL per minute per 1.73 m² (P<.001). The mean change between preoperative and 3-month follow-up eGFR was 10.1 mL per minute per 1.73 m² (P<.001). The mean preoperative, postoperative, and 3-month follow-up creatinine values were 1.0, 1.1, and 1.1 mg/dL, respectively (Table 3). There were 50 patients who had a decrease in eGFR from preoperative to postoperative levels. On both univariate and multivariate analyses, the only factor that independently predicted for a decrease in eGFR was ischemia time (P=.02).

Table 3.

Renal Functional Outcomes

	eGFR (mg/dL)	P value
Preoperative eGFR	78.3	–
Immediate postoperative eGFR	71.5	–
3 months follow up eGFR	68.2	–
Median difference in eGFR (preoperative and immediate postoperative)	6.7	P<.001
Median difference in eGFR (preoperative and 3 month follow-up)	10.1	P<.001

eGFR, estimated glomerular filtration rate.

In the sub-analysis comparing small (≤4 cm) and large (>4 cm) renal tumors, despite the longer warm ischemia times for tumors >4 cm (25.9 vs. 29.5 minutes, P=.04), there was no statistically significant difference in the complication rates between the two groups (P=.07) (Table 4). Finally, there were no perioperative or postoperative deaths, and the mean hospital stay was 2.0 days (range 1–8).

Table 4.

Peri-Operative Data and Complications Stratified by Tumor Size (>4 vs. ≤4 cm)

Groups	Tumors ≤4	Tumors >4	P value
Patients	77	23	–
Mean tumor size (cm) (range)	2.1 (0.9–4)	5.2 (4–9)	–
Mean warm ischemia time (min)	25.9	29.5	0.04
Mean hospitalization (days)	2.1	2.6	0.314
Open conversions	2	3	0.078
Hemorrhage	4	4	0.071
Positive margins	1	1	0.531
Transfusions	4	4	0.071
Overall complications	7	6	0.07

Only 1 recurrence (1%) was recorded. The patient presented with a hilar recurrence with tumor extension to the renal vein 30 months after PN, and subsequently underwent an open RN. The pathology report revealed a high-grade clear cell RCC. Six months after the procedure the patient shows no evidence of the disease.

Discussion

LPN has become a viable option for the minimally invasive treatment of RCN. The procedure was initially indicated for patients with small, exophytic renal tumors.^10,11 Prior studies have shown size limitations with concern of local recurrence and complications. Lifshitz and colleagues reported an increased complication rate associated with larger tumor size.¹² Gill and co-workers reported outcomes in a large multicenter cohort comparing OPN with LPN for patients with a T1 renal mass. Multivariate analysis showed that patients undergoing LPN had a significantly shorter operative time, shorter hospital stay, and less blood loss compared with OPN. However, LPN was associated with a higher rate of postoperative complications (24.9% vs. 19.2%), including postoperative bleeding (3.52 times that of OPN). The severity of hemorrhage was higher in LPN patients as well with more patients undergoing a postoperative embolization or re-exploration. The odds of a requiring a secondary procedure in the LPN group was 3.05 times compared to the OPN cohort.¹³ While this study represented the results of very experienced laparoscopic surgeons, the elevated complication rate for LPN may have been the result of the inclusion of these surgeons' learning curves. In contrast to LPN, which was first performed in 1993, OPN has a longer history and the surgeons performing these procedures did not have their learning curve incorporated into the data collected.

In a more recent study, Gill and colleagues reported on their extensive experience with 800 LPN, which were retrospectively stratified by time era. When comparing the earliest cases (first 276) with the most recent cases (last 235), they found that warm ischemia times were shorter (14.4 vs. 31.9 minutes) and postoperative complications (hemorrhage, urine leak, and open conversion) were less (8.5% vs. 22.1%). In addition, renal functional outcomes improved with a lower percent decrease in eGFR (10.6% vs. 17.9%). When stratified by tumor size (≤2, 2.1–4, and >4 cm), there were no statistically significant differences in ischemia times or complication rates.¹⁴

In the current study, the overall complication rate was 13% with hemorrhage being the most common complication (6%). When stratified based on tumor size (≤4 m and >4 cm), complication rates were comparable indicating that with experience, LPN is a reasonable option for selected larger tumors. In our series 5 (5%) patients required an open conversion. Four conversions were due to surgeon preference and were not associated with an intraoperative complication. One patient required conversion (OPN) due to significant intraoperative bleeding. Richstone and colleagues analyzed their experience with more than 347 LPN cases reporting an open conversion rate of (4%).¹⁵ Gill and colleagues reported open conversion in 16 LPN cases (2.1%) with 15 patients undergoing LPN and 1 patient requiring and open RN.¹⁴ We recognize that our present cohort differs from many reports in the literature since it reflects only patient outcomes after extensive laparoscopic experience with exclusion of our initial learning curve. However, with greater experience we have also incorporated increasingly challenging tumors with respect to size and position within the kidney.

With the evolution of the LPN technique, several high-volume centers have reported their experience with challenging central and hilar tumors.^16,17 Early in our experience we demonstrated complications in 6 out of 12 patients with hilar tumors.¹⁸ In the current series, 14 hilar tumors were treated with LPN with no intraoperative and only one postoperative complication (urine leak). While ureteral catheter placement is not generally performed for LPN at our center, complex hilar tumors are treated with intraoperative 5F ureteral catheter placement to aid in precise closure of the collecting system. Additionally, while we typically clamp only the renal artery, in hilar tumors we clamp both the artery and vein as even a small amount of bleeding can compromise tumor excision and precise collecting system reconstruction.

Renal functional outcomes are a critical factor when selecting a treatment modality for renal masses. Warm ischemia-reperfusion injury remains a challenge and a major area of controversy in LPN. Lane and colleagues examined the effects of different factors on renal functional outcomes after LPN, suggesting that warm ischemia time is the major modifiable surgical factor that significantly impacts postoperative renal function. Each additional minute after 20 minutes of warm ischemia was associated with a slightly larger decrease in glomerular filtration rate. The same group illustrated that renal function decreases immediately after LPN and returns to a new baseline state within 3 weeks postoperatively.¹⁹ Gill and coworkers reported similar outcomes (serum Cr) for patients undergoing LPN compared with OPN. Patients with normal baseline serum creatinine (≤1.4 mg/dL), two functioning kidneys, and a unilateral tumor had a nadir creatinine (≥90 days postoperative) of >1.5 mg/dL in 8.0% and 8.7% of the LPN and OPN cohorts, respectively.¹⁴ In our series immediate postoperative eGFR decreased compared with preoperative levels likely as a result of temporary postoperative dehydration. During 3-month follow-up eGFR decreased significantly compared with preoperative eGFR.

The malignancy rate in our cohort was 80%, with 79% being RCC variants. Only two (2%) patients had positive surgical margins in the final pathology report. Although there is still limited data regarding the long-term oncological follow-up after LPN, intermediate follow-up data have shown oncological outcomes comparable to contemporary OPN.^20,21 An important issue when evaluating the long-term efficacy of oncological surgery is local recurrence. In our series, we have one patient with a documented local recurrence found on postoperative CT scan.

Our experience with LPN has evolved with changes in surgical technique as well as in our level of surgeon experience. We now routinely use the intraoperative ultrasonography both for the purposes of identifying tumor characteristics as well as to identify the presence and absence of blood flow using the CFM. This has reduced our complications related to intraoperative bleeding and has helped to reduce operative times by accurately identifying persistent blood flow from the renal vessels or accessory vessels. In addition, we recognize that surgical volume and experience have greatly contributed to our improvements in clinical outcomes in this recent cohort.

Conclusions

In our contemporary cohort of the most current 100 LPNs, we have implemented a highly developed surgical technique that includes a complete hilar dissection, routine use of intraoperative ultrasonography with CFM, and meticulous parenchymal re-construction. Although our technique has not changed tremendously with the most recent 100 cases, our experience level has improved our patient outcomes. In addition, even select larger and complex hilar tumors can be managed with this technique.

Footnotes

Disclosure Statement

No competing financial interests exist.

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