Laparoscopic and Robotic Partial Nephrectomy With Controlled ...

Laparoscopic and Robotic Partial Nephrectomy With Controlled Hypotensive Anesthesia to Avoid Hilar Clamping: Feasibility, Safety and Perioperative Functional Outcomes Rocco Papalia,* Giuseppe Simone, Mariaconsiglia Ferriero, Manuela Costantini, Salvatore Guaglianone, Ester Forastiere and Michele Gallucci From the Departments of Urology “Regina Elena” (RP, GS, MF, SG, MG) and Anesthesiology “Regina Elena” (EF), National Cancer Institute and Laboratory of Molecular Medicine and Biotechnology, Department of Clinical Pathology, University Campus Bio-Medico of Rome (MC), Rome, Italy

Abbreviations and Acronyms ASA ⫽ American Society of Anesthesiologists CH ⫽ controlled hypotension LPN ⫽ laparoscopic PN MAP ⫽ mean arterial pressure PN ⫽ partial nephrectomy RAPN ⫽ robotic assisted PN RENAL ⫽ radius or maximal diameter in cm, exophytic/ endophytic properties, nearness of tumor to collecting system or sinus in mm, anterior/posterior, hilar tumor touches main renal artery or vein and location relative to polar lines WIT ⫽ warm ischemia time Submitted for publication August 3, 2011. Study received institutional review board approval. Supplementary material for this article can be obtained at www.jurology.com. * Correspondence: Department of Urology “Regina Elena,” National Cancer Institute, Via Elio Chianesi 53, 00144, Rome, Italy (telephone: ⫹390652665005; FAX: ⫹390652666983; e-mail: [email protected]).

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Purpose: We evaluated the feasibility and safety of laparoscopic and robotic assisted partial nephrectomy with controlled hypotensive anesthesia to avoid hilar clamping and eliminate renal ischemia. Materials and Methods: A total of 60 patients with renal tumors who were candidates for nephron sparing surgery and had no contraindication to hypotensive anesthesia underwent partial nephrectomy without hilar clamping and with controlled hypotension during tumor excision. A total of 40 laparoscopic partial nephrectomies and 20 robotic assisted partial nephrectomies were done. All patients who were candidates for laparoscopic or robotic assisted partial nephrectomy regardless of tumor site, size or growth pattern were included in study. The surgical field was assessed for bleeding and visibility using a numerical rating scale. Results: Median tumor size was 3.6 cm (range 1.8 to 10), median operative time was 2 hours (range 1 to 3.5), median blood loss was 200 ml (range 30 to 700 ml) and median hospital stay was 3 days (range 3 to 8). All margins were negative. The median duration of controlled hypotension with a median mean arterial pressure of 65 mm Hg (range 55 to 70) was 14 minutes (range 7 to 16). No patient required intraoperative transfusion but 4 (6.6%) required transfusion postoperatively. Complications developed postoperatively in 3 patients, ie port site bleeding, hemorrhage and hematoma, respectively. Median preoperative and postoperative serum creatinine was 0.9 and 1.10 mg/dl, respectively. The median preoperative and postoperative estimated glomerular filtration rate was 87.20 and 75.60 ml/minute/1.73 m2, respectively. Conclusions: Controlled hypotension allowed laparoscopic and robotic assisted partial nephrectomy to be done without renal hilar clamping. All procedures were completed safely and perioperative outcomes are encouraging. Key Words: kidney, kidney neoplasms, nephrectomy, robotics, ischemia SEVERAL technical modifications of LPN and RAPN aim to decrease or eliminate warm ischemia, although a limited WIT of 20 to 40 minutes is considered safe to prevent permanent renal damage.1,2 In any case the safe duration of WIT during PN remains controversial.

Recent publications describe how each minute of ischemia counts and PN without vascular clamping may decrease the risk of acute renal failure and chronic kidney disease.3– 6 To eliminate warm ischemia Gill et al recently reported a novel zero ischemia technique for LPN and RAPN.7

0022-5347/12/1874-1190/0 THE JOURNAL OF UROLOGY® © 2012 by AMERICAN UROLOGICAL ASSOCIATION EDUCATION

Vol. 187, 1190-1194, April 2012 Printed in U.S.A. DOI:10.1016/j.juro.2011.11.100

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RESEARCH, INC.

PARTIAL NEPHRECTOMY WITH HYPOTENSIVE ANESTHESIA TO AVOID HILAR CLAMPING

The 2 major components of the technique are 1) selective branch microdissection of the renal artery/ vein into the renal sinus and 2) transient, pharmacologically induced decreased blood pressure timed to coincide precisely with excision of the deep part of the tumor. In our series we used the technique described by Gill et al7 only for hilar tumors. For peripheral tumors CH was started after complete isolation of the kidney and the tumor and was maintained throughout the resection time. At our institution we have always avoided hilar clamping for PN by performing superselective transarterial embolization preoperatively as the first step of LPN in select cases.8 To evaluate the feasibility and safety of LPN and RAPN with CH we enrolled in the study only patients with an ASA score of 1 or 2 without any contraindication to hypotensive anesthesia, including heart disease, severe anemia, coronary artery disease, congestive heart failure, poorly controlled hypertension, increased intracranial pressure, significant cerebrovascular disease, or a low flow state to the liver or kidney. Hypotensive anesthesia is a safe technique that has been used for half a century to decrease bleeding and provide a satisfactory bloodless surgical field. CH is defined as a decrease of systolic blood pressure to 80 to 90 mm Hg, a decrease of MAP to 50 to 65 mm Hg or a 30% decrease of baseline MAP.9 We present our initial experience with LPN and RAPN with CH in 60 consecutive patients without hilar clamping and report the perioperative outcome of this technique. We evaluated whether CH makes LPN and RAPN feasible without the need to clamp the renal pedicle.

MATERIALS AND METHODS Between December 2010 and June 2011, 60 patients underwent zero ischemia LPN (40) or RAPN (20). Data were collected in a prospectively maintained institutional database. Study inclusion criteria were all patients with a single tumor who were considered candidates for LPN or RAPN regardless of tumor site, size or growth pattern. Renal mass anatomical features were recorded according to the PADUA (preoperative aspects and dimensions used for an anatomical) classification score and the RENAL nephrometry score (see table).10,11 The mean RENAL score was 7.9 (median 7, range 4 to 10). The only study exclusion criterion was an anesthesiology contraindication to CH, including congenital heart disease, severe anemia, coronary artery disease, congestive heart failure, poorly controlled hypertension, increased intracranial pressure, significant cerebrovascular disease or a low flow state to the liver or kidney. During the study period 5 patients did not meet inclusion criteria due to an ASA score of greater than 2. All procedures were done by a single surgeon with extensive experience with LPN and RAPN. Informed con-

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PADUA score anatomical aspects and RENAL nephrometry score No. Pts PADUA Tumor size (cm): Less than 4 4.1-7 Greater than 7 Longitudinal location: Superior Middle Inferior % Exophytic: Greater than 50 Less than 50 Endophytic Renal rim: Lat Medial Renal sinus involvement: No Yes Urinary collecting system involvement: No Dislocated/infiltrated Face: Anterior Posterior RENAL Radius, tumor size as maximal diameter (cm): Less than 4 Greater than 4-less than 7 Greater than 7 % Endophytic, exophytic: Less than 50 Greater than 50 Nearness of tumor deepest portion to collecting system or sinus (mm): Greater than 7 Less than 7-greater than 4 Less than 4 Face: Anterior Posterior Location relative to polar lines: Entirely above upper or below lower line Lesion crosses line Mass greater than 50% across line, crosses axial renal midline or entirely between lines Tumor abuts main renal artery or vein

36 18 6 20 22 18 12 26 22 38 22 56 4 51 9 37 23

36 18 6 22 26 12 28 8 22 28 32 32 22 6 4

sent was obtained from all patients. The study received institutional review board approval.

Preoperative Evaluation All patients underwent 1 mm slice computerized tomography with 3-phase acquisition or magnetic resonance imaging scan with 2 to 3 mm cuts to better delimit tumor site, depth and collecting system proximity. For this study serum creatinine was documented preoperatively, at discharge home and 1 month postoperatively. The estimated glomerular filtration rate, calculated using the modification of diet in renal disease formula, was documented preoperatively and at discharge home.

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Controlled Hypotension The aim of CH is to lower MAP while maintaining adequate perfusion to all vital organs. Since hypotensive anesthesia was limited to the level needed to decrease bleeding in the surgical field, the degree of hypotension was individualized. CH was induced only after isolating the kidney and tumor, and before incising the renal parenchyma around the renal mass. It lasted only for the time needed to perform PN. Meticulous monitoring is essential for patient safety during hypotensive anesthesia. Preoperative management included administering 2 l crystalloid intravenous fluid to expand intravascular volume and sampling arterial blood gas. Intraoperative management included electrocardiographic monitoring, invasive blood pressure and oxygen saturation measurement, end tidal carbon dioxide, temperature, blood loss and urinary output. During postoperative management attention was given to blood pressure, heart rate and electrocardiogram. The latter monitoring particularly included the V5 lead with ST segment analysis, which helps detect cardiac ischemia. We also noted analgesia, drain output and fluid balance. Rebound hypertension could be a concern during this period.9 After hypotension was induced the blood pressure required to minimize blood loss was maintained by adjusting the amount of hypotensive agents. To achieve the desired MAP we used a nitroglycerine infusion rate of 5 ␮g/kg per minute with a supplemental bolus of 50 to 100 ␮g.

Zero Ischemia PN A transperitoneal approach was used in all cases. An intraoperative pressure of 14 mm Hg was used to create pneumoperitoneum. After achieving access to the retroperitoneal space Gerota’s capsule was opened. The kidney was completely freed and mobilized to allow circumferential exposure of the tumor. When possible, a cuff of fat tissue over the tumor was preserved to maneuver the mass during resection. Hilar vessels were never clamped. Laparoscopic ultrasound was done to identify the tumor and establish a safe resection area. For peripheral tumors the renal parenchyma was incised with a monopolar scissor a few mm below the renal tumor and the dissection plane was found. During dissection specific vascular branches supplying the tumor were identified, clipped

using Hem-o-lok® clips or microclips and transected (part A of figure). Tumor excision was continued and completed with cold scissors, using electrocautery when required. After the tumor was removed the specimen and the PN bed were inspected for potential positive margins. The specimen was entrapped in a 10 mm entrapment bag and removed. Frozen section of the specimen was done in all patients to evaluate margin status. The surgeon assessed surgical field quality regarding bleeding and visibility on the numerical rating scale introduced by Fromme12 and Boezaart13 et al (see Appendix). After tumor excision was completed and renorrhaphy began blood pressure was gradually restored to the individual level of each patient to ensure effective hemostasis. Hemostasis was completed by placing a parenchymal suture (part B of figure). Renal defect closure was concluded by placing Surgicel® in the PN bed. It was maintained in place using interrupted sutures with medium to large Hem-o-lok clips placed at each end. For central and hilar tumors selective hilar microdissection was done according to the technique of Gill et al.7 Vessels supplying the tumor were identified, selectively clip ligated with Hem-o-lok clips and transected with cold scissors (part C of figure). In these cases CH was induced only during excision of the deepest part of the tumor.

RESULTS The zero ischemia procedure with CH was successfully completed in all patients. Conversion to open surgery and hilar clamping were not needed. Median tumor size was 3.6 cm (range 1.8 to 10), median operative time was 2 hours (range 1 to 3.5), median blood loss was 200 ml (range 30 to 700) and median hospital stay was 3 days (range 3 to 8). Pelvicalyceal repair was done in 20 patients (33%). Median times for tumor excision and suturing were 13 (range 5 to 16) and 16 minutes (range 14 to 22), respectively. Median CH duration at a median MAP of 65 mm Hg (range 55 to 70) was 14 minutes (range 7 to 16). Median nadir MAP was 60 mm Hg (range 55 to 65) for a median of 6 minutes (range 4 to 8).

A, vessel supplying tumor is clipped with microclip. B, parenchymal suture. C, selective microdissection of renal vessels supplying tumor.

PARTIAL NEPHRECTOMY WITH HYPOTENSIVE ANESTHESIA TO AVOID HILAR CLAMPING

Bleeding grades in the study group were 3 and 4. Intraoperatively no complications occurred and no blood transfusion was needed. One packed red blood cell transfusion was necessary in 4 patients (Clavien grade 2) postoperatively. Early postoperative complications were noted in 2 patients and late postoperative complications were noted in 1. There was port site bleeding in 1 case on postoperative day 1 (Clavien grade 3B). A male patient with hemorrhage (Clavien grade 3A) on postoperative day 3 was treated with transarterial superselective embolization. In another patient a retroperitoneal hematoma (Clavien grade 2) developed, which was treated conservatively. Histopathological evaluation revealed clear cell renal cell carcinoma in 46 patients (76.6%), type 2 papillary renal cell carcinoma in 2 (3.3%), type 1 papillary renal cell carcinoma in 2 (3.3%), chromophobe carcinoma in 3 (5%), oncocytoma in 4 (6.6%), angiomyolipoma in 2 (3.3%) and multilocular cystic nephroma in 1 (1.6%). All margins were negative. Median hemoglobin preoperatively and postoperatively at discharge home was 14.2 (IQR 13–14.7) and 11.3 gm/dl (IQR 10.2–12.5), respectively. Median serum creatinine preoperatively and postoperatively at discharge home was 0.9 (IQR 0.79 –1.03) and 1.10 mg/dl (IQR 0.87–1.20), respectively. The median estimated glomerular filtration rate preoperatively and postoperatively was 87.20 (IQR 77.40 –101.20) and 75.60 ml/minute/1.73 m2 (IQR 64.10 –91.20), respectively. One-month median postoperative serum creatinine was 1 mg/dl (IQR 0.89 –1.13).

DISCUSSION PN is currently the treatment of choice, when feasible.14 The duration of renal ischemia remains the main technical variable that affects renal function. Thompson et al evaluated the renal consequences of WIT in patients with a solitary kidney treated with PN.3 Longer WIT was associated with an increased risk of acute renal failure in the postoperative period and with new onset stage IV chronic kidney disease during followup. Our study confirms these previous findings that the duration of renal ischemia is the largest modifiable risk factor during PN in the solitary or 2 kidney setting.6 Recent evidence showed how hilar clamping produces a significant decrease in renal function in the treated kidney, which can be evaluated by 99mtechnetium-diethylenetriaminepentaacetic acid renal scan.15 As estimated by scintigraphy, the affected kidney is damaged when WIT exceeds 28 minutes during PN under the pneumoperitoneum. Thus, efforts to limit or eliminate ischemia time should be considered when performing PN, mainly in cases of

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a solitary kidney or impaired renal function. To avoid hilar clamping zero ischemia procedures were introduced.8,11 Although strong evidence suggests that any amount of clamp time is detrimental to renal function, to our knowledge these findings have not been widely reproduced or accepted to date as alternatives to hilar clamping. Factors predicting renal functional outcomes after PN are tumor size and WIT.6 Tumor size must be considered an independent variable of outcome while WIT can be decreased significantly by the skill of an experienced surgeon.3 Since each minute counts when the renal hilum is clamped during PN,3 it is desirable to establish the feasibility and safety of surgical techniques without hilar clamping. From this perspective we evaluated whether CH makes it possible to avoid clamping the renal pedicle during LPN and RAPN. The capacity of CH to decrease blood loss was discussed during the previous half century and in 1966 the first controlled study was published.16 This study of 2 series of 115 patients with CH and 116 control patients revealed a significant 50% decrease in blood loss when MAP was decreased to 55 to 65 mm Hg. The risk of tissue hypoxia and the difficulty of evaluating the risk were consistent. However, no specific complications were seen in a large series of patients who underwent severe CH (MAP less than 50 mm Hg) for a prolonged duration.17 The early study by Thompson et al showed that hypotensive anesthesia in patients scheduled for total hip arthroplasty resulted in significantly lower intraoperative blood loss and operative time than in a normotensive group.18 No significant differences were seen in mortality or morbidity in terms of cerebral, cardiovascular, renal and hepatic function between the hypotensive and normotensive groups. In our study CH effectiveness during LPN or RAPN without hilar clamping was evaluated in all eligible cases regardless of tumor site or size. Notably CH was induced only after completely isolating the kidney and identifying the renal mass. CH allowed us to incise the renal parenchyma and proceed with LPN and RAPN with acceptable bleeding (grade 3– 4).12,13 We evaluated surgical field bleeding using the scale reported by Fromme12 and Boezaart13 et al since we believe that it provides an objective measure that directly describes the surgical field observed by the surgeon. To minimize the amount of hypotensive anesthesia for peripheral tumors CH was started just before incising the renal parenchyma. Identification and clip ligation of specific vascular branches were not possible without hilar clamping due to bleeding impeding the procedure. For the 12 hilar tumors ultra selective microdissection was done to identify specific branches feeding the tumor. In these cases CH

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was started only after clip ligation and section of the identified feeding vessels. No anesthesia related complications were noted in our series but each patient had an ASA score of 1 or 2. Even if a new era is starting by avoiding hilar clamping during PN, we must consider the current limits of these procedures. Zero ischemia LPN and RAPN are not current candidates as the standard for all urologists since they are technically challenging and, thus, require surgeons to have extensive experience with minimally invasive surgery. Renal blood flow interruption via pedicle clamping may be needed during PN, especially for complex tumors with deep parenchymal invasion. Thus, early hilar isolation may always be beneficial for clamp placement if excess bleeding occurs or adequate hemostasis is not achieved at acceptable hypotension levels. This is particularly mandatory for less advanced laparoscopists. Concerning CH, patients with coronary disease, heart failure, poorly controlled hypertension, increased intracranial pressure, significant cerebrovascular disease, a low flow state to the liver or kidney, or severe anemia are not candidates. Notably most patients in our clinical practice do not have contraindications to hypotensive anesthesia (ASA class 1 or 2). Our aim was to verify the feasibility and safety of LPN and RAPN with CH and present our perioper-

ative results. Further evaluation of functional outcomes is under way at our institutions. Longer followup and further studies are needed to evaluate intermediate and long-term renal functional outcomes.

CONCLUSIONS In our experience LPN and RAPN with CH were feasible and safe. Preliminary results were encouraging. Available data are not adequately mature to determine long-term functional outcomes and ascertain how much zero ischemia LPN and RAPN could be reproducible.

APPENDIX Surgical Field Quality Grade

Assessment

0 1 2 3

No bleeding, cadaveric condition. Slight bleeding, no suctioning required. Slight bleeding, occasional suctioning required. Slight bleeding, frequent suctioning required. Bleeding threatens surgical field few secs after suction is removed. Moderate bleeding, frequent suctioning required, bleeding threatens surgical field directly after suction is removed. Severe bleeding, constant suctioning required. Bleeding appears faster than can be removed by suction. Surgical field severely threatened, surgery usually not possible.

4 5

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13. Boezaart AP, van der Merwe J and Coetzee A: Comparison of sodium nitroprusside- and esmololinduced controlled hypotension for functional endoscopic sinus surgery. Can J Anaesth 1995; 42: 373. 14. Zini L, Perrotte P, Capitanio U et al: Radical versus partial nephrectomy: effect on overall and noncancer mortality. Cancer 2009; 115: 1465. 15. Choi JD, Park JW, Choi JY et al: Renal damage caused by warm ischaemia during laparoscopic and robot-assisted partial nephrectomy: an assessment using Tc 99m-DTPA glomerular filtration rate. Eur Urol 2010; 58: 900. 16. Eckenhoff JE and Rich JC: Clinical experiences with deliberate hypotension. Anesth Analg 1966; 45: 21. 17. Kerr AR: Anesthesia with profound hypotension for middle ear surgery. Br J Anaesth 1977; 49: 447. 18. Thompson GE, Miller RD, Stevens WC et al: Hypotensive anesthesia for total hip arthroplasty: a study of blood loss and organ function (brain, heart, liver, and kidney). Anesthesiology 1978; 48: 91.