- Email: [email protected]
Laparoscopic Kidney Orthotopic Transplant: Preclinical Study in the Pig Model
Laparoscopic Kidney Orthotopic Transplant: Preclinical Study in the Pig Model B. He, G.C. Musk, L. Mou, G.L. Waneck, and L. Delriviere ABSTRACT Background. Laparoscopic surgery has rapidly expanded in clinical practice replacing conventional open surgery over the last three decades. Laparoscopic donor nephrectomy has been favored due to its multiple benefits. The aim of this study was to explore the safety and feasibility of kidney transplantation by a laparoscopic technique in a pig model. Materials and methods. The study was approved by the university animal ethics committee. Eight female pigs (Sus Scrofra, weighing 45–50 kg) were divided into 2 groups: group I included 4 animals that underwent laparoscopic kidney orthotopic transplantation on the left side. The right kidney was remained functional in situ. The pigs recovered and were observed for 1 week. In the 4 hosts group II pigs underwent a laparoscopic kidney transplantation on the left side. With simultaneous clipping of the right ureter. After recovery, the pigs were observed for 4 weeks. A laparotomy for examination was performed prior to euthanasia. Results. All 4 group I pigs survived for 1 week. The laparotomy showed normal graft perfusion with wall patent renal artery and vein as well as satisfactory urine output upon transection of ureter in 3 hosts. Renal artery stenosis occurred in one pig. In The Immediate kidney graft function was achieved in 3 group II pigs. The fourth died following extubation due to laryngospasm despite a functional graft. The average creatinine levels were 195.5 mol/L on day 3; 224.5 mol/L at week 1; 127 mol/L at week 2; 182.7 umol/L at week 3; and 154.7 umol/L at week 4. Conclusion. Laparoscopic kidney transplantation was feasible and safe in a pig model with immediate graft function. This study will provide further evidence to support application of laparoscopic technique to human kidney transplant. APAROSCOPIC SURGERY has expanded over the last 3 decades to replace open procedures due to its multiple benefits. Laparoscopic donor nephrectomy has become the standard of care at most transplant centers.1–5 However, the surgical technique for the recipient has not changed since the first successful procedure in the 1950s. It requires an open incision with the kidney graft placed at the pelvis, which lacks protection from contact sport injury or trauma. It becomes a difficult surgery when a third or more transplantation is needed for a recipient. Therefore, the aim of this study was to develop a laparoscopic technique for kidney transplantation in the region of the native kidney using a preclinical pig model.
L
MATERIALS AND METHODS The study was approved by our university animal ethics committee according to the guidelines of the National Health and Medical
Research Council of Australia code of practice for the care and use of animals for scientific purposes. Eight live female pigs (Sus Scrofa), weighing 45–50 kg, were transported to the Large Animal Facility (LAF) of the university 2 weeks prior to surgery for acclimatization. The pigs were housed in a pen above the floor. They were fed a maintenance diet (Grower, West feeds Pty Ltd, Australia) and allowed free access to tap water. Daily care was provided by the staff of the LAF. From Sir Charles Gairdner Hospital (B.H., L.M., L.D.), Western Australia Liver-Kidney Transplant Service, Perth, Australia; the Animal Care Service (G.C.M.), The University of Western Australia, Perth, Australia; and the Transplant Immunology Laboratory (G.L.W.), The University of Western Australia, Perth, Australia. Address reprint requests to A/Prof. Bulang He, Sir Charles Gairdner Hospital, Western Australia Liver-Kidney Transplant Service, Hospital Ave, Nedlands, Perth, Western Australia 6009. E-mail: [email protected]
0041-1345/13/$–see front matter http://dx.doi.org/10.1016/j.transproceed.2013.01.056
© 2013 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710
1776
Transplantation Proceedings, 45, 1776 –1779 (2013)
LAPAROSCOPIC KIDNEY ORTHOTOPIC TRANSPLANT These 8 pigs were divided into 2 groups: group I (n ⫽ 4) underwent laparoscopic orthotopic kidney transplantation on the left side with the right kidney remaining functional in situ. recovery after the pigs were observed for 7 days. The 4 group II; pigs underwent laparoscopic orthotopic kidney transplantation on left side with simultaneous clipping of right ureter. After recovery the pigs were observed for 4 weeks.
Anesthesia Food was withheld for 12 hours prior to surgery, but the pigs were allowed free access to water. Anesthesia was induced with a combination of Zoletil (4.4 mg/kg) and xylazine (2.2 mg/kg) by intramuscular injection in the neck. An auricular vein was cannulated to administer propofol (1 mg/kg) intravenously (IV) to achieve an adequate depth of anesthesia for tracheal intubation using a cuffed endotracheal tube (Portex, Soft Seal Cuff, 8.0-mm ID; SIMS Portex Limited, UK). Pancuronium was administered (0.1 mg/kg IV by intermittent bolus) for neuromuscular blockade. Anesthesia was maintained with isoflurane delivered in 100% oxygen. Mechanical ventilation was commenced immediately after oral intubation of the trachea with a tidal volume of 10 –15 mL/kg and peak inspiratory pressure up to 25 cm H2O. Ventilator settings were adjusted to achieve normocapnia (end tidal CO2 35– 45 mm Hg). The depth of anesthesia was assessed subjectively by a veterinarian throughout the procedure to alter the concentrations of delivered isoflurane. Every 5 minutes the auricular artery was also cannulated for direct blood pressure measurements. We recorded oxyhemoglobin saturation; end tidal CO2, invasive blood pressure, central venous pressure, and pharyngeal temperature with continuous monitoring of the electrocardiogram. Hartmann’s solution administered IV (10 mL/kg/h) was increased if the mean arterial blood pressure fell below 60 mm Hg. Gelofusin (2–5 mL/kg/h) was administered IV if required. In addition, a urethral catheter that was inserted to observe urine output during surgery was removed upon completion of the procedure.
Surgical Procedure Following induction of general anesthesia, the pig was placed in right lateral recumbency. An infusion port (French 6, single lumen) in the left internal jugular vein was employed for blood sampling and IV fluid therapy. The Hanson camera port was inserted via an open incision at 3 cm to the left of midline and 4 cm cranial to the umbilicus. Pneumoperitoneum was established before camera examination of the intraperitoneal structures. Under direct vision, we placed 2 operating ports in the left lower abdomens. The port for a fan retractor was inserted on the right side 1 cm to the midline and 2 cm cranial to the umbilicus. The assistant port, on the left side above the camera port. These five ports formed a letter V upon drawing a line from the assistant to the operating port. The left kidney was identified and the bowel dissected medially to expose the renal artery, vein, and ureter. The renal artery was dissected to the region of aorta and the renal vein to the vena cava to obtain the longest possible vessels. After completion of the dissection, the kidney was mobilized from its attachments. The ureter was divided below the lower pole. Then, a small midline incision (6 cm) was made in the lower abdomen. The peritoneum remained intact until delivery of the kidney graft. Heparin (1500 IU) was given intravenously prior to renal artery and vein clamping using an endoscopic bulldog (B Brown, Germany) and division. The kidney was delivered and perfused immediately with cold (4°C) Ross perfusion fluid (Orion, Australia, Ross solution 1 L ⫹ Heparin 10,000 IU). A
1777 marking stitch was placed at the upper and lower corners of the renal vein using 6-0 Prolene to facilitate its manipulation during the anastomosis. The kidney was preserved with cold (4°C) perfusion fluid until implantation. The kidney was then implanted at the orthotopically using a laparoscopic technique. The renal artery was anastomosed end to end to the renal artery stump by interrupted 6-0 Prolene sutures; the renal vein, in end-to-end fashion to the renal vein stump using a posterior side was anastomosis with a 6-0 Prolene running suture and anteriorly by interrupted stitches or a separate running suture. In the meantime, the kidney graft was continuously flushed with cold (4°C) normal saline via an extra 5-mm port. Following completion of the anastomosis, the kidney graft was reperfused by removing the venous bulldog and arterial bulldog. Furosemide (40 mg) was delivered IV after kidney reperfusion. The ureter was spatulated and anastomosed in end-to-end fashion using interrupted 5-0 Polydioxane (PDS) sutures. The kidney graft was fixed at the upper pole, lateral side and lower pole by 3 4-0 PDS sutures. Hemostasis was checked before the wound and port sites were closed in layers. In group II, the pig was repositioned in the left decubitus position. A Hanson port inserted upon open visualization allowed 2 more 12-mm ports to be placed under vision. The right kidney was exposed to identify the right ureter. The endoclips were applied to ligate the right ureter completely. At the end of surgery, Tramadol (100 mg) was administered intramuscularly and bupivacaine (0.25%, 40 mL) injected at the wound and port sites for analgesia. The anesthetic was weaned and the pig extubated. Vital signs were observed and recorded every 15 minutes for 6 hours then twice a day for 1 week in group I and 4 weeks in group II. The urine output was monitored by checking the individual pen floor. Doppler ultrasound was performed to examine blood flow to the graft at the end of the surgery. Water and food were supplied to the pig after a wakening. Blood tests were performed before and after surgery, as well as prior to euthanasia. Additional tests were obtained at day 3 as well as weeks 1, week 2, week 3, and week 4 for group II. A laparotomy examination was performed under anesthesia at the end of the study prior to euthanasia.
RESULTS
All 4 group I pigs recovered from surgery and survived for 1 week without urine leakage or wound infection. The renal artery and vein waveforms were normal on Doppler ultrasound. The hemoglobin was stable pre- and postsurgery. Laparotomy examination showed that the left kidney graft was mild hydronephrotic with hydroureter, but in 3 pigs it was well perfused with a patent renal artery and vein. Urine output was satisfactory via transection of the ureter in these 3 pigs. Renal artery stenosis with thrombosis occurred in 1 pig, there was no venous stenosis. The right kidney was normal in situ in all 4 pigs. Three group II pigs recovered uneventfully with immediate kidney graft function. One animal died following extubation due to laryngospasm upon autopsy. At laparotomy examination, the left transplanted kidneys appeared normal with mild hydronephrosis and hydroureter above the anastomosis. Mucosal edema at the ureteral anastomotic sites was observed in all pigs, but the ureter was patent. The right kidney was severely hydronephrotic with parenchymal atrophy (Fig 1). The
1778
HE, MUSK, MOU ET AL
Fig 1. Kidney changes in group II. (Left) Severe hydronephrosis and hydroureter above ligation in right kidney. (Right) Normal parenchyma and mild hydronephrosis in left transplanted kidney.
blood results of hemoglobin and creatinine from both groups are shown in Table 1. DISCUSSION
Laparoscopic surgery has been widely employed in surgical practice as a result of its multiple benefits. The success of laparoscopic vascular anastomosis has made the organ transplantation possible. Currently, the surgical technique for kidney transplantation has remained as a conventional open procedure. The incision is about 15–20 cm long with a unavoidable transection of the muscular layers. In addition, the disadvantage of this technique is that the kidney graft is located in the pelvis, where it is relatively superficial and susceptible to injury during contact sports or trauma. A third or fourth kidney transplant can also be difficult due to iliac vessels adhesions from the previous surgery. Therefore, orthotopic transplantation provides an alternative option with long-term patient and graft survival comparable to conventional heterotopic kidney transplantation.6 Nevertheless, open orthotopic kidney transplantation has not been favored as it is more difficult requiring long midline incision or a posterolateral lumbotomy, cutting massive muscles.6,7 As a result, more analgesia is required and the recovery takes longer. This study has shown that orthotopic kidney transplantation can be performed safely by laparo-
scopic surgery, requiring only a small midline (6 cm) incision. Application of the laparoscopic technique for human orthotopic kidney transplantation is a novel approach in selected recipients. Over last decade, there have been 3 single case reports of kidney transplantation using either a laparoscopic or a robotic technique.8 –10 Obviously, laparoscopic surgery for kidney transplantation is extremely demanding, as the vessel anastomosis must be performed under time pressure. Since last year, there have been an increasing number of case reports of kidney transplantation by a laparoscopic or robotic technique.11–13 However, in these reports the kidney graft was placed in the iliac fossa with the renal vein anastomosed to the external iliac vein and renal artery to the external iliac artery. To date, there have been no reports of orthotopic laparoscopic kidney transplantation, as in this report using a pig model. Laparoscopic orthotopic kidney transplantation may provide an alternative approach for human kidney transplantation. In particular, it may be useful for younger recipients who wish to enjoy active sports or patients who have already had 2 previous kidney transplantations. This study has demonstrated that orthotopic kidney transplantation can be performed safely using a laparoscopic technique. The advantages included a smaller incision, avoidance of muscle transection, less pain and quicker recovery. An end-to-end anastomosis using continuous running sutures, tends to promote renal vein stenosis due to the purse-string effect. Therefore, the anterior side was anastamosed with interrupted stitches to overcome stenosis, a problem also reported in open auto-kidney transplantation.14 Obviously, in this experiment, laparoscopic kidney transplantation only requires a small incision (6 cm) in the lower midline to deliver the graft. The incision was created by opening the skin and fascia at the midline and opening the muscular layer in the para-midline, making the incision function like a valve to effectively reduce the gas leak. This incision is time and cost saving as after the kidney graft is placed in the orthotopic location for vessel anastomosis, it does not need to be closed/sealed to prevent a gas leak, thus minimizing graft warm ischemic time. On postmortem examination we demonstrated that the quality of laparoscopic vessel anastomosis was reliable. A repair stitch was satisfactory when there was a leak at the anastomosis. It was noticed that the vessel anastomotic time was much longer using the laparoscopic technique. Continuous running cold fluid over the kidney has helped to slow down graft rewarming. Nevertheless, laparoscopic
Table 1. Blood Results for Hb (g/L) and Cr (umol/L) Group
Blood
Presurgery
Postsurgery
I
Hb Cr Hb Cr
102 98.7 110.7 106.3
108 131 120.7 146.3
II
Cr, creatinine; Hb, hemoglobin.
Day 3
Day 7
Day 14
Day 21
Day 28
120 191.7
108.6 121 120.7 202
108 132
115.7 182.7
112 154.7
LAPAROSCOPIC KIDNEY ORTHOTOPIC TRANSPLANT
vessel anastomotic time will be reduced significantly with further practice and with refinement of the laparoscopic instruments. In addition, care needs to be taken to align the ends of the renal artery adequately during the anastomosis to avoid the necessity of a repair stitch and the subsequent possibility of stenosis. There was no urine leakage or other complications during 4 weeks’ observation. This study provided further evidence for translating laparoscopic orthotopic kidney transplantation techniques to the clinical setting. REFERENCES 1. Tooher R, Boult M, Maddern GJ, Rao MM. Final report from the ASERNIP-S audit of laparoscopic live-donor nephrectomy. ANZ J Surg. 2004;74:961–963. 2. Merlin TL, Scott DF, Rao MM, et al. The safety and efficacy of laparoscopic live donor nephrectomy: a systematic review. Transplantation. 2000;70:1659 –1666. 3. Melcher ML, Carter JT, Duh Q-Y, et al. More than 500 consecutive laparoscopic donor nephrectomies without conversion or repeated surgery. Arch Surg. 2005;140:835– 840. 4. Hadjianastassiou VG, Johnson RJ, Rudge CJ, Mamode N. 2509 living donor nephrectomies, morbidity and mortality, including the UK introduction of laparoscopic donor surgery. Am J Transplant. 2007;7:2532–2537.
1779 5. He B, Mitchell A, Deliriviere L, Shannon T, Pemberton R, Tan A, Bremner A, Vivian J. Laparoscopic donor nephrectomy. ANZ J Surg. 2011;81:159 –163. 6. Musquera M, Peri LL, Alvarez-Vijande R, Oppenheimer F, Gil-Vernet JM, Alcaraz A. Orthotopic kidney transplantation: an alternative surgical technique in selected patients. Eur Urol. 2010; 58(6):927–933. 7. Paduch DA, Barry JM, Arsanjani A, Lemmers MJ. Indication, surgical technique and outcome of orthotopic renal transplantation. J Urol. 2001;166:1647–1650. 8. Hoznek A, Zaki SK, Samadi DB, et al. Robotic assisted kidney transplantation: an initial experience. J Urol. 2002;167: 1604 –1606. 9. Rosales A, Salvador JT, Urdaneta G, et al. Laparoscopic kidney transplantation. Eur Urol. 2010;57:164 –167. 10. Giulianotti P, Gorodner V, Sbrana F, et al. Robotic transabdominalkidney transplantation in a morbidly obese patient. Am J Transplant. 2010;10:1478 –1482.5. 11. Modi P, Rizvi J, Pal B, et al. Laparoscopic kidney transplantation: an initial experience. Am J Transplant. 2011;11:1320 –1324. 12. Boggi U, Vistoli F, Signori S, et al. Robotic renal transplantation: first European case. Transplant Int. 2011;24(2):213–218. 13. Benedetti E. Robotic intra-peritoneal kidney transplant in obese recipients. Paper presented at: American Transplant Congress: April 30 –May 4, 2011; Philadelphia, PA. 14. Jochmans I, Lerut E, Heedfeld V, et al. Reproducible model for kidney autotransplantation in pigs. Transplant Proc. 2009;41: 3417–3421.
L
MATERIALS AND METHODS The study was approved by our university animal ethics committee according to the guidelines of the National Health and Medical
Research Council of Australia code of practice for the care and use of animals for scientific purposes. Eight live female pigs (Sus Scrofa), weighing 45–50 kg, were transported to the Large Animal Facility (LAF) of the university 2 weeks prior to surgery for acclimatization. The pigs were housed in a pen above the floor. They were fed a maintenance diet (Grower, West feeds Pty Ltd, Australia) and allowed free access to tap water. Daily care was provided by the staff of the LAF. From Sir Charles Gairdner Hospital (B.H., L.M., L.D.), Western Australia Liver-Kidney Transplant Service, Perth, Australia; the Animal Care Service (G.C.M.), The University of Western Australia, Perth, Australia; and the Transplant Immunology Laboratory (G.L.W.), The University of Western Australia, Perth, Australia. Address reprint requests to A/Prof. Bulang He, Sir Charles Gairdner Hospital, Western Australia Liver-Kidney Transplant Service, Hospital Ave, Nedlands, Perth, Western Australia 6009. E-mail: [email protected]
0041-1345/13/$–see front matter http://dx.doi.org/10.1016/j.transproceed.2013.01.056
© 2013 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710
1776
Transplantation Proceedings, 45, 1776 –1779 (2013)
LAPAROSCOPIC KIDNEY ORTHOTOPIC TRANSPLANT These 8 pigs were divided into 2 groups: group I (n ⫽ 4) underwent laparoscopic orthotopic kidney transplantation on the left side with the right kidney remaining functional in situ. recovery after the pigs were observed for 7 days. The 4 group II; pigs underwent laparoscopic orthotopic kidney transplantation on left side with simultaneous clipping of right ureter. After recovery the pigs were observed for 4 weeks.
Anesthesia Food was withheld for 12 hours prior to surgery, but the pigs were allowed free access to water. Anesthesia was induced with a combination of Zoletil (4.4 mg/kg) and xylazine (2.2 mg/kg) by intramuscular injection in the neck. An auricular vein was cannulated to administer propofol (1 mg/kg) intravenously (IV) to achieve an adequate depth of anesthesia for tracheal intubation using a cuffed endotracheal tube (Portex, Soft Seal Cuff, 8.0-mm ID; SIMS Portex Limited, UK). Pancuronium was administered (0.1 mg/kg IV by intermittent bolus) for neuromuscular blockade. Anesthesia was maintained with isoflurane delivered in 100% oxygen. Mechanical ventilation was commenced immediately after oral intubation of the trachea with a tidal volume of 10 –15 mL/kg and peak inspiratory pressure up to 25 cm H2O. Ventilator settings were adjusted to achieve normocapnia (end tidal CO2 35– 45 mm Hg). The depth of anesthesia was assessed subjectively by a veterinarian throughout the procedure to alter the concentrations of delivered isoflurane. Every 5 minutes the auricular artery was also cannulated for direct blood pressure measurements. We recorded oxyhemoglobin saturation; end tidal CO2, invasive blood pressure, central venous pressure, and pharyngeal temperature with continuous monitoring of the electrocardiogram. Hartmann’s solution administered IV (10 mL/kg/h) was increased if the mean arterial blood pressure fell below 60 mm Hg. Gelofusin (2–5 mL/kg/h) was administered IV if required. In addition, a urethral catheter that was inserted to observe urine output during surgery was removed upon completion of the procedure.
Surgical Procedure Following induction of general anesthesia, the pig was placed in right lateral recumbency. An infusion port (French 6, single lumen) in the left internal jugular vein was employed for blood sampling and IV fluid therapy. The Hanson camera port was inserted via an open incision at 3 cm to the left of midline and 4 cm cranial to the umbilicus. Pneumoperitoneum was established before camera examination of the intraperitoneal structures. Under direct vision, we placed 2 operating ports in the left lower abdomens. The port for a fan retractor was inserted on the right side 1 cm to the midline and 2 cm cranial to the umbilicus. The assistant port, on the left side above the camera port. These five ports formed a letter V upon drawing a line from the assistant to the operating port. The left kidney was identified and the bowel dissected medially to expose the renal artery, vein, and ureter. The renal artery was dissected to the region of aorta and the renal vein to the vena cava to obtain the longest possible vessels. After completion of the dissection, the kidney was mobilized from its attachments. The ureter was divided below the lower pole. Then, a small midline incision (6 cm) was made in the lower abdomen. The peritoneum remained intact until delivery of the kidney graft. Heparin (1500 IU) was given intravenously prior to renal artery and vein clamping using an endoscopic bulldog (B Brown, Germany) and division. The kidney was delivered and perfused immediately with cold (4°C) Ross perfusion fluid (Orion, Australia, Ross solution 1 L ⫹ Heparin 10,000 IU). A
1777 marking stitch was placed at the upper and lower corners of the renal vein using 6-0 Prolene to facilitate its manipulation during the anastomosis. The kidney was preserved with cold (4°C) perfusion fluid until implantation. The kidney was then implanted at the orthotopically using a laparoscopic technique. The renal artery was anastomosed end to end to the renal artery stump by interrupted 6-0 Prolene sutures; the renal vein, in end-to-end fashion to the renal vein stump using a posterior side was anastomosis with a 6-0 Prolene running suture and anteriorly by interrupted stitches or a separate running suture. In the meantime, the kidney graft was continuously flushed with cold (4°C) normal saline via an extra 5-mm port. Following completion of the anastomosis, the kidney graft was reperfused by removing the venous bulldog and arterial bulldog. Furosemide (40 mg) was delivered IV after kidney reperfusion. The ureter was spatulated and anastomosed in end-to-end fashion using interrupted 5-0 Polydioxane (PDS) sutures. The kidney graft was fixed at the upper pole, lateral side and lower pole by 3 4-0 PDS sutures. Hemostasis was checked before the wound and port sites were closed in layers. In group II, the pig was repositioned in the left decubitus position. A Hanson port inserted upon open visualization allowed 2 more 12-mm ports to be placed under vision. The right kidney was exposed to identify the right ureter. The endoclips were applied to ligate the right ureter completely. At the end of surgery, Tramadol (100 mg) was administered intramuscularly and bupivacaine (0.25%, 40 mL) injected at the wound and port sites for analgesia. The anesthetic was weaned and the pig extubated. Vital signs were observed and recorded every 15 minutes for 6 hours then twice a day for 1 week in group I and 4 weeks in group II. The urine output was monitored by checking the individual pen floor. Doppler ultrasound was performed to examine blood flow to the graft at the end of the surgery. Water and food were supplied to the pig after a wakening. Blood tests were performed before and after surgery, as well as prior to euthanasia. Additional tests were obtained at day 3 as well as weeks 1, week 2, week 3, and week 4 for group II. A laparotomy examination was performed under anesthesia at the end of the study prior to euthanasia.
RESULTS
All 4 group I pigs recovered from surgery and survived for 1 week without urine leakage or wound infection. The renal artery and vein waveforms were normal on Doppler ultrasound. The hemoglobin was stable pre- and postsurgery. Laparotomy examination showed that the left kidney graft was mild hydronephrotic with hydroureter, but in 3 pigs it was well perfused with a patent renal artery and vein. Urine output was satisfactory via transection of the ureter in these 3 pigs. Renal artery stenosis with thrombosis occurred in 1 pig, there was no venous stenosis. The right kidney was normal in situ in all 4 pigs. Three group II pigs recovered uneventfully with immediate kidney graft function. One animal died following extubation due to laryngospasm upon autopsy. At laparotomy examination, the left transplanted kidneys appeared normal with mild hydronephrosis and hydroureter above the anastomosis. Mucosal edema at the ureteral anastomotic sites was observed in all pigs, but the ureter was patent. The right kidney was severely hydronephrotic with parenchymal atrophy (Fig 1). The
1778
HE, MUSK, MOU ET AL
Fig 1. Kidney changes in group II. (Left) Severe hydronephrosis and hydroureter above ligation in right kidney. (Right) Normal parenchyma and mild hydronephrosis in left transplanted kidney.
blood results of hemoglobin and creatinine from both groups are shown in Table 1. DISCUSSION
Laparoscopic surgery has been widely employed in surgical practice as a result of its multiple benefits. The success of laparoscopic vascular anastomosis has made the organ transplantation possible. Currently, the surgical technique for kidney transplantation has remained as a conventional open procedure. The incision is about 15–20 cm long with a unavoidable transection of the muscular layers. In addition, the disadvantage of this technique is that the kidney graft is located in the pelvis, where it is relatively superficial and susceptible to injury during contact sports or trauma. A third or fourth kidney transplant can also be difficult due to iliac vessels adhesions from the previous surgery. Therefore, orthotopic transplantation provides an alternative option with long-term patient and graft survival comparable to conventional heterotopic kidney transplantation.6 Nevertheless, open orthotopic kidney transplantation has not been favored as it is more difficult requiring long midline incision or a posterolateral lumbotomy, cutting massive muscles.6,7 As a result, more analgesia is required and the recovery takes longer. This study has shown that orthotopic kidney transplantation can be performed safely by laparo-
scopic surgery, requiring only a small midline (6 cm) incision. Application of the laparoscopic technique for human orthotopic kidney transplantation is a novel approach in selected recipients. Over last decade, there have been 3 single case reports of kidney transplantation using either a laparoscopic or a robotic technique.8 –10 Obviously, laparoscopic surgery for kidney transplantation is extremely demanding, as the vessel anastomosis must be performed under time pressure. Since last year, there have been an increasing number of case reports of kidney transplantation by a laparoscopic or robotic technique.11–13 However, in these reports the kidney graft was placed in the iliac fossa with the renal vein anastomosed to the external iliac vein and renal artery to the external iliac artery. To date, there have been no reports of orthotopic laparoscopic kidney transplantation, as in this report using a pig model. Laparoscopic orthotopic kidney transplantation may provide an alternative approach for human kidney transplantation. In particular, it may be useful for younger recipients who wish to enjoy active sports or patients who have already had 2 previous kidney transplantations. This study has demonstrated that orthotopic kidney transplantation can be performed safely using a laparoscopic technique. The advantages included a smaller incision, avoidance of muscle transection, less pain and quicker recovery. An end-to-end anastomosis using continuous running sutures, tends to promote renal vein stenosis due to the purse-string effect. Therefore, the anterior side was anastamosed with interrupted stitches to overcome stenosis, a problem also reported in open auto-kidney transplantation.14 Obviously, in this experiment, laparoscopic kidney transplantation only requires a small incision (6 cm) in the lower midline to deliver the graft. The incision was created by opening the skin and fascia at the midline and opening the muscular layer in the para-midline, making the incision function like a valve to effectively reduce the gas leak. This incision is time and cost saving as after the kidney graft is placed in the orthotopic location for vessel anastomosis, it does not need to be closed/sealed to prevent a gas leak, thus minimizing graft warm ischemic time. On postmortem examination we demonstrated that the quality of laparoscopic vessel anastomosis was reliable. A repair stitch was satisfactory when there was a leak at the anastomosis. It was noticed that the vessel anastomotic time was much longer using the laparoscopic technique. Continuous running cold fluid over the kidney has helped to slow down graft rewarming. Nevertheless, laparoscopic
Table 1. Blood Results for Hb (g/L) and Cr (umol/L) Group
Blood
Presurgery
Postsurgery
I
Hb Cr Hb Cr
102 98.7 110.7 106.3
108 131 120.7 146.3
II
Cr, creatinine; Hb, hemoglobin.
Day 3
Day 7
Day 14
Day 21
Day 28
120 191.7
108.6 121 120.7 202
108 132
115.7 182.7
112 154.7
LAPAROSCOPIC KIDNEY ORTHOTOPIC TRANSPLANT
vessel anastomotic time will be reduced significantly with further practice and with refinement of the laparoscopic instruments. In addition, care needs to be taken to align the ends of the renal artery adequately during the anastomosis to avoid the necessity of a repair stitch and the subsequent possibility of stenosis. There was no urine leakage or other complications during 4 weeks’ observation. This study provided further evidence for translating laparoscopic orthotopic kidney transplantation techniques to the clinical setting. REFERENCES 1. Tooher R, Boult M, Maddern GJ, Rao MM. Final report from the ASERNIP-S audit of laparoscopic live-donor nephrectomy. ANZ J Surg. 2004;74:961–963. 2. Merlin TL, Scott DF, Rao MM, et al. The safety and efficacy of laparoscopic live donor nephrectomy: a systematic review. Transplantation. 2000;70:1659 –1666. 3. Melcher ML, Carter JT, Duh Q-Y, et al. More than 500 consecutive laparoscopic donor nephrectomies without conversion or repeated surgery. Arch Surg. 2005;140:835– 840. 4. Hadjianastassiou VG, Johnson RJ, Rudge CJ, Mamode N. 2509 living donor nephrectomies, morbidity and mortality, including the UK introduction of laparoscopic donor surgery. Am J Transplant. 2007;7:2532–2537.
1779 5. He B, Mitchell A, Deliriviere L, Shannon T, Pemberton R, Tan A, Bremner A, Vivian J. Laparoscopic donor nephrectomy. ANZ J Surg. 2011;81:159 –163. 6. Musquera M, Peri LL, Alvarez-Vijande R, Oppenheimer F, Gil-Vernet JM, Alcaraz A. Orthotopic kidney transplantation: an alternative surgical technique in selected patients. Eur Urol. 2010; 58(6):927–933. 7. Paduch DA, Barry JM, Arsanjani A, Lemmers MJ. Indication, surgical technique and outcome of orthotopic renal transplantation. J Urol. 2001;166:1647–1650. 8. Hoznek A, Zaki SK, Samadi DB, et al. Robotic assisted kidney transplantation: an initial experience. J Urol. 2002;167: 1604 –1606. 9. Rosales A, Salvador JT, Urdaneta G, et al. Laparoscopic kidney transplantation. Eur Urol. 2010;57:164 –167. 10. Giulianotti P, Gorodner V, Sbrana F, et al. Robotic transabdominalkidney transplantation in a morbidly obese patient. Am J Transplant. 2010;10:1478 –1482.5. 11. Modi P, Rizvi J, Pal B, et al. Laparoscopic kidney transplantation: an initial experience. Am J Transplant. 2011;11:1320 –1324. 12. Boggi U, Vistoli F, Signori S, et al. Robotic renal transplantation: first European case. Transplant Int. 2011;24(2):213–218. 13. Benedetti E. Robotic intra-peritoneal kidney transplant in obese recipients. Paper presented at: American Transplant Congress: April 30 –May 4, 2011; Philadelphia, PA. 14. Jochmans I, Lerut E, Heedfeld V, et al. Reproducible model for kidney autotransplantation in pigs. Transplant Proc. 2009;41: 3417–3421.