Research Article

Comparison of Off-Clamp and On-Clamp Partial Nephrectomy and Its Impact on the Renal Functional Outcome: A Single Institute Experience in South Indian Patients

Sivakumar Mahalingam1, Anand Raja2*, Kathiresan Narayanaswamy3, Krishna Kumar Rathinam4
1,2Department of Surgical Oncology, Cancer Institute (WIA), Adyar, Chennai, India
3Cancer Institute (WIA), Dr. S.Krishnamurthy Campus, Apollo Speciality Hospitals, Chennai, India
4Department of Nuclear medicine, Cancer Institute (WIA), Adyar , Chennai, India


*Corresponding author: Arturo Navarro-Martin, Radiation Oncology Department, Catalan Institute of Oncology, Spain

Published: 20 Jan, 2018
Cite this article as: Navarro-Martin A, de Luna CJ, Fuentes R, Fernández MDA, Jové J. Extracranial Oligometastasis in Non- Small Cell Lung Cancer. Clin Oncol. 2018; 3: 1398.

Abstract

Introduction: Partial nephrectomy (PN) or nephron sparing surgery is the standard of care for all feasible renal tumors < 4cm. Multiple partial nephrectomy techniques have evolved to reduce the ischemic injury to the renal parenchyma with variable effects on renal function. Off clamp technique avoid ischemic injury to the renal parenchymal altogether and better preserves the long term renal function, delaying or avoiding the development of chronic kidney disease. The aim of the study is to compare off-clamp and on-clamp techniques of partial nephrectomy and its impact on the renal functional outcome.
Methods: Patient who underwent partial nephrectomy from January 2007 to December 2016 were analyzed retrospectively. The partial nephrectomy renal units were grouped into off-clamp and on-clamp (warm and cold ischemia) group. The demographic data, clinico-pathological factors, pre-operative and post-operative glomerular filtration rate (GFR) as measured by radioisotope renography Tc99m-DTPA (diethylenetriaminepentacetate) scan, surgical margin, complications (Clavien Dindo classification), hospital stay, blood loss and blood transfusion rate were compared and analyzed between the two group.
Results: Twenty three eligible rental units who underwent partial nephrectomy between January 2007 and December 2016 were included for analysis. The mean age was 46 years. One was a pediatric patient with bilateral wilms tumor aged 2 years and he underwent staged bilateral partial nephrectomy. Majority had clear cell histology 78% (18/23), papillary histology 13% (3/23) and two wilms tumor. All had open partial nephrectomy except two had laparoscopic assisted procedure. Ten (43%) underwent on-clamp technique out of which one had warm ischemic and nine had cold ischemic clamping technique. The mean clamping time was 35 minutes for the available six rental units in the on-clamp group. Thirteen (57%) patients underwent off-clamp technique. There is no difference in the age, sex, tumor site, size, grade, margins, histology type, overall complications, blood loss, blood transfusion and hospital stay among the two groups. All surgical margins were negative in both groups. The preoperative mean GFR (Tc99m-DTPA scan) was comparable 70.13 and 67.78 ml/min/1.73m2 (p=0.765) between the on-clamp and off-clamp group. The percentage GFR decrease in the postoperative period (>3 months) was 0.28 % in the off-clamp group compared to 8 % in the on-clamp group.
Conclusion: Off-clamp partial nephrectomy is a feasible and oncologically safe technique. It is a promising technique which avoids the ischemic renal parenchymal injury after partial nephrectomy. The renal functional outcome is better with off-clamp technique compared to on-clamp partial nephrectomy. The limitation is the non-availability of standardization of techniques and prospective randomized trials.
Keywords: Nephrectomy; Chronic kidney disease; Glomerular filtration rate; Radioisotope renography


Introduction

Partial nephrectomy is the standard of care for all feasible renal tumors < 4cm with proven long term outcomes [1]. Pedicle clamping technique is done to ensure blood-less surgical field and ease the resection. Prolonged renal ischemia time is associated with high risk of adverse renal function outcomes even after partial nephrectomy [2-4]. To reduce or avoid the ischemia time and maximize the functional outcomes various techniques are being practiced [5]. No guidelines or recommendations are available on the optimal technique to maximize the renal functional outcomes. The data on long-term renal functional outcomes after partial nephrectomy or comparison between off-clamp and on-clamp partial nephrectomy is not available from India.


Methods

Between January 2007 and December 2016, the case records of all patients who underwent partial nephrectomy were taken up for the study. Patient who underwent partial nephrectomy and final histopathology report with malignancy was included for the study. Patient who had benign histology were excluded from the study.
Study design: Retrospective observation study
Statistical method: Frequency tables describe the clinicopathological factors and outcomes. The student t-test and Pearson Chi-square test compares the clinico-pathological variables, shortterm outcomes and preoperative renal functional (Tc99m-DTPA scan) between the off-clamp and on-clamp partial nephrectomy group. Overall survival outcome was calculated by Kaplan meier test.
Preoperative evaluation: Hemogram, renal function test- GFR, creatinine clearance, blood urea and creatinine, liver function test, coagulation profile, chest x ray, contrast enhanced computer tomography (CECT) abdomen and pelvis. The GFR measurement was performed using radioisotope renography Tc99m-DTPA scan. CT angiogram with renal vessel reconstruction was done based on the complexity of the lesion.
Surgical technique: Midline transperitoneal or retroperitoneal flank approach. Preoperative ureteric stenting was routinely used during the initial periods. But after 2014 ureteric stenting was selectively used for complex lesions located near the collecting system. Kidney was mobilized and renal vessels were separately dissected out. For on-clamp technique vascular clamps were applied to both vein and artery and unclamped once resection and renorraphy is completed. Sterile ice slush was packed all around the kidney in case of cold ischemia technique. The renal vessels are not clamped in offclamp technique. Tumor is excised enbloc with the perinephric fat and gerota facia covering the tumor with target margin of 5 mm to 10 mm. Renorraphy is done using 2-0 absorbable vicryl sutures and then renopexy completes the procedure.
Follow up: Follow up visits was done every three months for first 3 years, every six months for the 4th and 5th year and then annually thereafter. At each visit a detailed clinical history, physical examination and blood urea & creatinine was done. Tc99m-DTPA renal scan was done after 3 to 6 months. Annual investigation with chest x-ray, CECT abdomen & pelvis.


Table 1

Another alt text

Table 1
Clinico-pathological variables comparable between the two groups.

Results

A total of twenty five rental units underwent partial nephrectomy. Twenty three units met the inclusion criteria. Two were excluded because of benign histology. All had open partial nephrectomy except two who had laparoscopic assisted procedure. Ten (43%) underwent on-clamp technique out of which one had warm ischemic and nine had cold ischemic clamping technique. The mean clamping time was 35 minutes for the available six rental units. Thirteen (57%) patients underwent off-clamp technique. The twenty three units were divided in to two group namely on-clamp and off-clamp group. The clinicopathological variables were comparable between both the two group and listed in the table 1. The short term outcomes like mean blood loss, blood transfusion rate, hospital stay, complications and thirty day mortality was comparable and listed in table 2. The Clavien Dindo grade II was the most common complication in both the group. Urine leak was reported in one patient after off-clamp technique which was managed conservatively by drain insertion. Re-exploration laparotomy and completion nephrectomy for bleeding on the day one postoperative day after off-clamp partial nephrectomy was done. Hematuria due to surgical bed pseudo-aneurysm on day nine for one patient in the on-clamp group was managed by embolizing it.
The preoperative mean GFR was comparable between the onclamp (70.13 ml/min/1.73m2) and off-clamp (67.78 ml/min/1.73m2) groups (p= 0.765). The comparison of the preoperative and postoperative (> 3 months) mean GFR was available for eleven rental units in off-clamp and six rental units in on-clamp technique. The percentage decline in the GFR post partial nephrectomy was less in off-clamp group 0.28% compared to the on-clamp group 8%. The preservation of post partial nephrectomy GFR (> 3months) was better with off-clamp technique 99.72% compared to the on-clamp group 92%. The decline in the post partial nephrectomy mean GFR within the group was not statistically significant because of the low power of the study. There are no local recurrences in either group. One patient died of systemic recurrence in the on-clamp group. The five years overall survival for all the twenty three partial nephrectomy rental units was 95%.


Table 2

Another alt text

Table 2
Short-term outcomes comparable between the two groups.

Discussion

The incidences of small renal masses (SRM) are on a raising trend due to the increase in abdominal imaging in the modern medicine [6]. The current standard for the management of high risk suspicious small renal masses is nephron sparing surgery or partial nephrectomy [7]. Various approaches and techniques of partial nephrectomy have emerged but no consensus or guidelines exist. Minimal invasive approaches are comparable with open partial nephrectomy. Robotic approach is gaining popularity with better short-term outcomes than open and laparoscopic approach [8,9]. The concern about radical nephrectomy is the effect on long term renal function outcomes, resulting in early CKD and then cardiac morbidity [10,11]. There is a paradigm shift to partial nephrectomy as standard of care for all feasible renal tumor < 4 cm, apart from its traditional indications. Partial nephrectomy with prolonged ischemia time will also have detrimental effect on the renal function outcomes [2-4].
The renal functional outcomes after partial nephrectomy depends on the modifiable risk factors like renal ischemia time, excisional volume loss, reconstructive methods and non-modifiable risk factors like location, size, age, comorbid conditions, preoperative GFR, previous renal disease or surgery [12]. The central dogma of the partial nephrectomy is to optimize the preservation of functioning nephrons by targeting the modifiable and non-modifiable risk factors but still remains controversial and area of active research [13]. Various technique like cold ischemia time using ice slush, selective arterial clamping, super selective clamping of higher order arteries, early unclamping of vessels, non clamping are used to reduce or avoid the renal ischemia thereby improving the preservation of renal function outcome [4,14].
Various studies has shown off-clamp partial nephrectomy is feasible, safe and avoids renal ischemia with better preservation of long-term renal function outcomes [15,16]. It is currently an emerging and good technique of partial nephrectomy which needs standardization. Open off-clamp partial nephrectomy is comparable and feasible by minimal invasive approaches [16,8]. Mearini et al from Italy compared open, laparoscopic and robotic off-clamp partial nephrectomy. They concluded the efficacy and safety of laparoscopic and robotic partial nephrectomy was comparable with the open technique with the additional benefit of reduced operative time, blood loss, on demand ischemia and rate of high grade complication [18].
Meta-analysis has compared on-clamp and off clamp partial nephrectomy and its effect on the renal function outcome. A metaanalysis in 2014 by Wentao Liu et al of ten retrospective studies comparing 728 off clamp and 1267 on-clamp technique reported superior long-term renal function preservation for the off- clamp technique [19]. Another meta-analysis in 2014 from United Kingdom that includes fourteen studies concluded improved long-term renal function for off-clamp than the on-clamp technique. A non-statistical significant trend towards increased blood loss and transfusion for offclamp technique was reported [20].
This study is one of its kinds as there is no published Indian data exist on comparison of on-clamp and off-clamp partial nephrectomy and its impact on renal functional outcomes. Another uniqueness of the study is the utilization of the Tc99m-DTPA scan for assessment and comparison of renal function in the available literature. Most studies have reported on estimated GFR (e-GFR). The limitation of this study is the retrospective nature, small power, non-availability of nephrometry score.


Conclusion

Partial nephrectomy is an underutilized procedure in India. But, with the increase in diagnosis of incidental small renal mass and awareness about this procedure, the partial nephrectomy procedures show an uptrend in recent years. India being the capital of diabetes with associated hypertension, the chance of progression to CKD is also high in our setting following nephrectomy. The need of the hour is to maximize the utilization of partial nephrectomy technique after standardization. In this context, the off-clamp technique is a promising one as it avoids the renal parenchymal ischemia and optimizes the renal function by minimizing or delaying the development of CKD.


References

  1. Delakas D, Karyotis I, Daskalopoulos G, Terhorst B, Lymberopoulos S and Cranidis A. Nephron-sparing surgery for localized renal cell carcinoma with a normal contralateral kidney: a European three-center experience. Urology. 2002;60(6):998-1002.
  2. Leppert JT, Lamberts RW, Thomas IC, Chung BI, Sonn GA, Skinner EC et al. Incident CKD after Radical or Partial Nephrectomy. J Am Soc Nephrol. 2017 Oct 10. pii: ASN.2017020136. doi: 10.1681/ASN.2017020136. [Epub ahead of print]
  3. Volpe A, Blute ML, Ficarra V, Gill IS, Kutikov A, Porpiglia F et al. Renal Ischemia and Function After Partial Nephrectomy: A Collaborative Review of the Literature. Eur Urol. 2015;68(1):61-74.
  4. Simmons MN, Lieser GC, Fergany AF, Kaouk J, Campbell SC. Association between warm ischemia time and renal parenchymal atrophy after partial nephrectomy. J Urol. 2013;189(5):1638-42.
  5. Simone G, Gill IS , Mottrie A, Kutikov A, Patard JJ, Alcaraz A et al. Indications, Techniques, Outcomes, and Limitations for Minimally Ischemic and Off-clamp Partial Nephrectomy: A Systematic Review of the Literature. Eur Urol. 2015;68(4):632-40.
  6. Mohammed S Al-Marhoon. Small Incidental Renal Masses in Adults. Review of the literature. Sultan Qaboos Univ Med J. 2010;10(2):196-202.
  7. Russo P, Huang W. The medical and oncological rationale for partial nephrectomy for the treatment of T1 renal cortical tumors. Urol Clin North Am. 2008;35(4):635-43.
  8. Choi JE, You JH, Kim DK, Rha KH and Lee SH. Comparison of perioperative outcomes between robotic and laparoscopic partial nephrectomy: a systematic review and meta-analysis. Eur Urol. 2015;67(5):891-901.
  9. Shen Z, Xie L, Xie W, Hu H, Chen T, Xing C et al. The comparison of perioperative outcomes of robot-assisted and open partial nephrectomy: a systematic review and meta-analysis. World J Surg Oncol. 2016;14(1):220.
  10. Choi SK and Song C. Risk of chronic kidney disease after nephrectomy for renal cell carcinoma. Korean J Urol. 2014;55(10):636-42.
  11. Li L, Lau WL, Rhee CM, Harley K, Kovesdy CP, Sim JJ, et al. Risk of chronic kidney disease after cancer nephrectomy. Nat Rev Nephrol. 2014;10(3):135-45.
  12. Antonelli A, Mari A, Longo N, Novara G, Porpiglia F, Schiavina R, et al. Role of Clinical and Surgical Factors for the Prediction of Immediate, Early and Late Functional Result and its Relationship with Cardiovascular Outcome After Partial Nephrectomy: Results from the Prospective Multicenter RECORd 1 Project. J Urol. 2017 Nov 14. pii: S0022-5347(17)77910-4.
  13. Mir MC, Ercole C, Takagi T, Zhang Z, Velet L, Remer EM, et al. Decline in renal function after partial nephrectomy: etiology and prevention. J Urol. 2015;193(6):1889-98.
  14. Lee JW, Kim H, Choo M, Park YH, Ku JH, Kim HH et al. Different methods of hilar clamping during partial nephrectomy: Impact on renal function. Int J Urol. 2014 Mar;21(3):232-6.
  15. Dente D, Paniccia T, Petrone D, Gaspari G, Tucci C, Rossetti R, et al. Open partial nephrectomy with no clamping of the pedicule: a good surgical option in treatment of renal cancer. Minerva Urol Nefrol. 2010;62(4):341-6.
  16. Petrasz P, Słojewski M and Sikorski A. Impact of "non-clamping technique" on intra- and postoperative course after laparoscopic partial nephrectomy. Wideochir Inne Tech Maloinwazyjne. 2012;7(4):275-9.
  17. Rais-Bahrami S, George AK, Herati AS, Srinivasan AK, Richstone L and Kavoussi LR. Off-clamp versus complete hilar control laparoscopic partial nephrectomy: comparison by clinical stage. BJU Int. 2012 May;109(9):1376-81.
  18. Mearini L, Nunzi E, Vianello A, Di Biase M and Porena M. Margin and complication rates in clampless partial nephrectomy: a comparison of open, laparoscopic and robotic surgeries. J Robot Surg. 2016;10(2):135-44.
  19. Wentao Liu, Yuan Li, Minfeng Chen, Li Gu, Shiyu Tong and Ye Lei. Off-Clamp Versus Complete Hilar Control Partial Nephrectomy for Renal Cell Carcinoma: A Systematic Review and Meta-Analysis. J End urol. 2014;28(5):567-76.
  20. Trehan A. Comparison of off-clamp partial nephrectomy and on-clamp partial nephrectomy: a systematic review and meta-analysis. Urol Int. 2014;93(2):125-34.