The modification and optimization of retroperitoneal laparoscopic radical 1 nephrectomy for the treatment of localized renal cell carcinoma

23 Background: We report our modified surgical technique of retroperitoneal laparoscopic 24 radical nephrectomy (RLRN) and assess its perioperative outcomes and postoperative 25 complications, with a focus on operative time (OT). 26 Methods: We retrospectively analyzed a single-center, single-surgeon cohort of 130 27 consecutive patients who underwent RLRN between January 2015 and March 2019. A study 28 group of 65 patients who received modified RLRN was compared with a control group of 65 29 patients who received classical RLRN. OT, estimated blood loss (EBL), perioperative 30 complications, postoperative first exhaust time (PFET), pathological stage, and postoperative 31 hospital stay (PHS) were compared between the two groups. 32 Results: All demographic, clinical, and pathological variables were comparable between the 33 groups. No differences were observed in perioperative complications (p=0.648), peritoneal 34 injuries (p=0.843), PFET (p=0.448), pathological stage (p=0.767), and PHS (p=0.304). The 35 modified RLRN group resulted in a signi ficantly reduced overall OT (53.8±8.4 min vs. 36 60.5±10.6 min, p =0.000 ), peritoneal injury intervention subgroup OT (56.3±9.8 min vs. 37 75.2±12.4 min, p =0.000 ), and EBL (55.7±10.1 mL vs. 62.3±11.6 mL, p=0.001) compared with 38 the classical RLRN group. We observed a significant reduction in OT and EBL but no increase 39 in postoperative complications, PFET, or PHS with modified versus traditional RLRN for 40 localized renal carcinoma. Conclusions: Findings from this study present a modified RLRN surgical technique that is 42 standardized, more precise, and has better practicability.

6 function was evaluated by ECT and was in the normal range. Bowel preparation was 112 performed the night before surgery and fasting for 8 h and drinking water for 2 h were 113 required before the operation. 114 115

Surgical procedures 116
The procedure was performed by adopting general anesthesia with endotracheal 117 intubation. The patient was placed in a 90-degree lateral decubitus position with the lumbar 118 bridge raised and tilted down the head side by 15° and the foot side 30°. Special objects were 119 placed on the front and back to prevent the patient from shifting. 120 After routine disinfection and towel laying, a transverse incision approximately 2.0 cm in 121 length was made 2.0 cm above the anterior superior iliac spine of the midline of the axilla to 122 cut through the skin and subcutaneous tissue. After the muscle and the dorsal fascia were 123 obtusely separated by vascular forceps, the index finger was inserted deep into the muscular 124 layer to push the peritoneum toward the ventral side. 125 The retroperitoneal cavity was dilated by an expander made of a double-layer sterilized 126 rubber glove that was injected with 500-800 mL of gas and continued to dilate for 1 min 127 before being removed from the body. 128 A 10-mm trocar was placed at site A (Figure 1). A 1-0 silk thread was placed in the 129 incision to prevent air from entering the retroperitoneal cavity. The prepared CO2 gas was 130 injected from the trocar and used to inflate to an abdominal pressure of 15.0 mmHg, and 131 then the laparoscope was placed into the retroperitoneal cavity. Under direct endoscopic view, 132 two 12-mm trocars were placed at point B (2.0 cm below the 12 costal margin of the posterior 7 axillary line) and point C (2.0 cm below the costal margin of the anterior axillary line) to ensure 134 no injury to the peritoneum. 135

Classical surgical technique 136
The first 65 cases were operated using classical RLRN as described by Gill et al. [6,15,16]. 137 Surgical procedures included: fully dissociating the posterior renal space in the dorsal side of 138 the kidney, then the anterior renal space in the ventral side, and ultimately the lower and 139 upper poles. The emphasis was on the anatomy of the renal pedicle, skeletonization of the 140 renal artery and vein, and vascular clipping and cutting. After complete resection of the kidney, 141 the specimen was placed in a homemade specimen bag and removed. A drainage tube 142 remained in the retroperitoneal cavity. If peritoneal injury resulted in pneumoperitoneum and 143 limited retroperitoneal visual field, a hole was added between the A and C incisions, in which 144 the assistant (a urologist or urology resident) could use auxiliary forceps to lift the peritoneum 145 to the ventral side. 146

Modified surgical technique 147
The 65 subsequent procedures for modified RLRN consisted of the following steps: 148 First, the removal of extraperitoneal adipose tissue ( Figure 2A). Under laparoscopic direct 149 vision, the extraperitoneal adipose tissue was dissected downward with an ultrasonic scalpel 150 and dissociated from the peritoneum and the lateral conical fascia and then placed into the 151 iliac fossae, so that the peritoneal reflection and peritoneum could be clearly identified, and 152 the retroperitoneal space was further enlarged. 153 Second, the dissociation of the anterior pararenal space. The lateral conical fascia was 154 incised from the side of the peritoneum reflection, and the peritoneum was separated to the 8 ventral side along the non-vascularized interval of the anterior pararenal space between the 156 perirenal fascia and the peritoneum ( Figure 2B). During this process, if gas leaked into the 157 abdominal cavity or injured the peritoneum, resulting in pneumoperitoneum, the rupture was 158 clipped with hem-o-lok clips. A small incision was cut at site D (Figure 1, 2 cm below the 159 costal margin of the midclavicular line), and a 5-mm trocar was placed for continuous 160 exhausting. After exhausting, the peritoneum could be pressed rapidly to the ventral side, and 161 the operating space of the retroperitoneal cavity was expanded again. 162 Third, the dissociation of the posterior pararenal space ( Figure 2C). The renal dorsal side was 163 dissociated along the anterior psoas space or the posterior renal fascia space until it reached 164 below the diaphragm, and then it was dissociated downward to the iliac fossa to fully 165 dissociate the dorsal side of the kidney. 166 Fourth, anatomy and ligation of renal pedicle vessels. When the posterior renal space 167 was fully dissected, renal artery pulsation was clearly visible behind the central fascia of the 168 kidney. After the renal artery was dissected and adequately skeletonized by ultrasonic bistoury, 169 it was cut and clamped with three clips ( Figure 2D). It was easy to handle the lower pole of 170 the kidney outside the perirenal fat sac, during which the ureters and gonadal vessels could 171 be easily found. The ureter was ligated and severed 10 cm below the lower pole of the kidney. 172 When lifting the left kidney, the renal vein, genital vein, lumbar vein, and central adrenal vein 173 may be clearly seen on the ventral and dorsal sides, and the inferior vena cava could also be 174 clearly seen on the right kidney ( Figure 2E). After clipping with three large clips, the renal vein 175 was cut off. 176 Finally, the dissociation of the upper pole of the kidney was completely isolated (Figure 9 2F). If the tumor did not invade the adrenal gland, it was generally retained. After observing 178 no active bleeding at the operating field, the kidney was placed in the specimen bag and 179 tightened. A drainage tube was placed in incision B and fixed. According to the size of the 180 specimen, incision C was extended to the ventral side, and the specimen was removed 181 completely. Extraperitoneal adipose tissue was cut off and removed from the body, and the 182 muscular layer, myofascial layer, and subcutaneous tissue were sutured with 2-0 absorbable 183 sutures. Finally, the incision was sutured intradermally with 4-0 absorbable sutures. 184

Postoperative care and follow-up 185
Patients were encouraged to begin off-bed activities on the first postoperative day and 186 allowed to start an oral liquid diet on the day of the anal exhaust. The drainage tube was 187 removed when the daily drainage volume was less than 10 mL. The patients were discharged 188 when their conditions remained stable after pathological diagnosis and drainage tube 189 removal. 190 Patients with a pathological stage of T1-2N0M0 did not receive adjuvant therapy and 191 were followed up every 3-6 months for 3 consecutive years and then annually. Some T3 192 patients received adjuvant therapy. T3 patients were followed up every 3 months for 2 193 consecutive years, every 6 months for the third year, and annually thereafter. However, the side hole of the channel operated by the ultrasonic scalpel was opened in the 288 modified group so that the smoke and exhaust gas generated by the ultrasonic scalpel would 289 be quickly discharged out of the body. The air circulation also reduced the frequency of the 290 lens blur and reduced the lens polishing time. The intake pneumoperitoneum pressure was 291 15.0 mmHg, and the exhaust was discharged through the side orifice and auxiliary orifice of 292 the abdominal cavity. The exhaust velocity was adjusted according to the pressure, and the 293 actual pressure fluctuated between 10 and 12.0 mmHg without affecting the visual field. 294 Through the above technical improvements, the modified RLRN procedure performed in 295 our operation group was carried out step by step according to the technical route, without 296 the problem of delaying the OT due to unexpected circumstances. In the modified group, the 297 average OT, especially in the peritoneal injury subgroup, and the intraoperative EBL were 298 significantly shorter than those in the control group. There was no intraoperative blood 299 transfusion and almost no intraoperative bleeding during the operation in some cases in both 300 groups. Furthermore, through the modification of the surgical procedure, the accessory renal 301 vein, gonadal vein, and central adrenal vein were dissected clearly, reducing the risk of 302 vascular injury and thus the time to hemostasis by accident. 303 We do not deny that the control of the renal pedicle is critical; however, procedural, 304 standardized, and precise surgical procedures can make the operation more repeatable and 305 practical. It may also help beginners to quickly master the technology, shorten the learning 306 curve, and thus be more conducive to the application of the technology. For obesity, perirenal 307 adhesions, hilar masses, vascular variations, and other complex conditions, the modified 308 method can be used. 309 The reported complications were mostly vascular injury and organ injury, which had 310 more serious and dangerous consequences and often required further surgical intervention 311 or conversion to open surgery [13,33,34]. In retroperitoneal laparoscopic surgery, peritoneal 312 injury was not uncommon; however, reported cases were not frequent. It might be that 313 peritoneal injury was often overlooked because serious consequences were not observed. 314 Through practice, our team found that retroperitoneal laparoscopic surgery, especially the 315 extensive resection of RLRN, had a higher incidence of peritoneal injury, with a total of 40 316 cases of peritoneal injuries occurring in 130 RLRN cases. Among them, 35 needed additional 317 assistance to better complete the consequent procedure. There were 18 cases of peritoneal 318 injury in the modified group and 17 cases in the classical group. Most of the injuries occurred 319 during the surgical procedure of separating peritoneal reflection and the anterior pararenal 320 space. In a survey of 24 medical centers, 63% of urologists admitted that peritoneal injury 321 significantly increased the difficulty of the remaining procedures [11]. This was probably due 322 to the peritoneal injury, which led to gas entering the abdominal cavity and increased 323 intraperitoneal pressure, thus causing greater compromise of the operative field and affecting 324 the consequent surgical procedure [10]. In the control group, after peritoneal injury, auxiliary 325 holes were added to the retroperitoneal cavity (generally located between points A-C or A-326 B), and then the peritoneum was lifted by the assistant with a separation clamp to ensure the 327 successful completion of subsequent surgery. Because the pneumoperitoneum in the 328 abdominal cavity could not be resolved, the operation scope became smaller, and the 329 auxiliary forceps had adverse effects on the operation of the surgeon in vivo and in vitro. 330 However, the method adopted by the modified technique group was simple, easy to operate, 331 and had little influence on the subsequent operation of the subgroup with peritoneal injury 332 after increasing the abdominal auxiliary control of exhaust. 333 The study also found that it was necessary to dissociate the non-vascular space between 334 the anterior pararenal space and the peritoneum in RLRN. The peritoneum is a very thin and 335 semi-permeable membrane. Between the anterior prerenal space and the peritoneum, CO2 336 gas will gradually enter the abdominal cavity through the peritoneum, progressively 337 increasing abdominal pressure and narrowing the retroperitoneal space, which also increases 338 the difficulty of the operation. In view of this, we can consider using the vent hole of the 339 abdominal cavity to maintain the pressure difference between the retroperitoneal cavity and 340 the abdominal cavity, so that the free peritoneum is pressed ventrally. Thus, a relatively large 341 surgical view in the retroperitoneal cavity is maintained to facilitate laparoscopic operation, 342 which can save OT and reduce the possibility of intraoperative injury. Although some cases 343 of peritoneal injury included an auxiliary trocar, the PFET was not prolonged, indicating that 344 the auxiliary hole had little interference with the abdominal cavity and did not affect the 345 postoperative recovery of gastrointestinal function. 346 The current study was not without limitations. First, it was a nonrandomized controlled 347 study using a historical cohort of different eras as a control group and involved a relatively 348 limited sample size. Second, patients in the modified technique group were operated after 349 the control group, which might have influenced the outcomes. Doctors' experience might 350 not be optimal when performing surgery in patients in the control group compared with the 351 modified group. However, this surgical team is a high-volume laparoscopic surgery group, 352 which has rich practical experience in both peritoneal and retroperitoneal surgery. As early as 353 2015, the total number of laparoscopic surgeries per year was over 300, and laparoscopic 354 nephrectomy or partial resection averaged over 200. Therefore, the impact might be limited. 355 Furthermore, due to the difference in mean follow-up time between the two groups, no 356 further comparative analysis of oncologic outcomes was performed. Considering that the 357 scope of surgical resection was the same, although the surgical procedure was modified, the 358 impact on tumor prognosis may also be limited. Randomized prospective studies can be 359 conducted to accumulate more data in order to obtain more reliable outcomes in the future.