UNCLASSIFIED The Obturator Nerve Reflex after Thulium Laser vs. Monopolar Transurethral Resection of Bladder Tumors: A Randomized Clinical trial Vahid Abedi Yarandi1, Fatemeh Khatami1, Seyed Mohammad Kazem Aghamir1* Purpose: Obturator nerve reflex is the surgery treatment side effect in patients with bladder cancers. This study was run to determine the obturator nerve reflex by Thulium laser versus monopolar Transurethral Resection of Bladder Tumors (TURBT). Materials and methods: After receiving the approval code IRCT20190624043991N4, one hundred and eighty- nine patients with bladder tumors from 2010 to 2016 were assessed, and among them, 35 patients were randomly assigned into two groups in a blinded manner; the first group (16 patients) received thulium laser and the second group (19 patients) were patients undergoing monopolar transurethral resection of bladder tumor after spinal an- algesia. Clinical data, including different variables such as; age, tumor characteristics, gender, operation dura- tion, types of leg jerking, and intraoperative complications, were recorded. The site of the obturator nerve was determined by nerve stimulation, anatomical landmarks, and ultrasonography. Leg jerking was compared in both groups. Results: Of the 35 patients, 28 cases were male, and 7 points were female. The mean ± SD (range) of age was 62.0 ± 6.9 (40-75) years in the Thulium laser group and 64.0 ± 7.1 (41-77) years in the monopolar TURBT group. The mean operation time was not different between the two groups significantly (P > 0.05). Leg jerking was reported in 25% and 63.1% of the patients in Thulium laser and monopolar TURBT groups, respectively (P < 0.05). Conclusion: Thulium laser is a more feasible and effective method to prevent leg jerking in patients with bladder cancer; so, it is recommended more than monopolar Transurethral. Keywords: monopolar TURBT; thulium laser; non-muscle-invasive bladder tumor; leg jerking INTRODUCTION Bladder cancer is one of the most common can-cers worldwide, and about 430000 new cases of bladder cancer were reported in 2012 (1). One of the treatment strategies for bladder cancer is transurethral resection of the bladder tumor (TUR-BT), resulting in long-term survival rates of 40%-60% (2). However, TUR-BT is unfortunately associated with some essen- tial substantial morbidities and complications such as obturator nerve reflex (ONR) and consequently adduc- tor muscles contraction that we call "Leg Jerking"(3, 4). It happens because the obturator nerve extends through the lateral wall of the bladder(5,6). It may result in blad- der perforation that is a risky event in these patients(4, 5). General anesthesia and local muscle relaxant injections are the suggested preferred methods of anesthesia in these patients. Different laser types are recommended for bladder cancers or upper urinary tract urothelial tumors(7). Hol- mium yttrium aluminum garnet laser (Ho: YAG) is ef- 1Department of Urology, The Affiliated Changzhou No. 2 People’s Hospital of Nanjing Medical University, Changzhou 213003, Jiangsu, China. 2Dalian Medical University, Dalian, Liaoning, China. *Correspondence: Lifeng Zhang, Department of Urology, The Affiliated Changzhou No. 2 People’s Hospital of Nanjing Medical University, Changzhou 213003, Jiangsu, China. Tel:+86 519 88123501. E-mail: nj-likky@163.com. **Department of Urology, The Affiliated Changzhou No. 2 People’s Hospital of Nanjing Medical University, Changzhou 213003, Jiangsu, China. PHONE:+86 519 88123501. E-mail: zuoli1978@hotmail.com. Received September 2019 & Accepted July 2021 fective but has disadvantages, including limited tissue collection for pathological studies(8,9). In 2005, the new technique of thulium laser (Tm: YAG) was suggested surgically generating a wavelength of 2 μm, which is much more helpful for resection in an aqueous medium (10). The use of thulium laser came to be the appropriate option in reducing leg jerking(11,12). This study was per- formed to compare the obturator Nerve reflex by Thuli- um laser versus monopolar Transurethral Resection of Bladder Tumor. MATERIALS AND METHODS The Ethics Committee approved the study of the School of Medicine- Tehran University of Medical Sciences (IR. TUMS.MEDICINE.REC.1396.4657) and the Iranian Registry of Clinical Trials (IRCT20190624043991N4). This study was designed based on clinical trial policies, and two groups of patients were blindly randomized into the two different intervention groups. After completing informed consent forms by patients, 189 patients with bladder tumors were referred to the study from 2010 Urology Journal/Vol 18 No. 6/ November-December 2021/ pp. 688-692. [DOI: 10.22037/uj.v0i0.5599] to 2016. Inclusion criteria were filling out the consent form, high risk of general anesthesia for surgery, and bladder tumor presence at the obturator nerve site, which included posterior-lateral, trigone area (Figure 1). Patients in their clinical examination and their pre- vious clinical records had no history of neurologic dis- ease (such as multiple sclerosis, stroke, and Parkinson's disease, diabetes, or discopathy that can affect spinal reflexes. The patients were excluded if there were mus- cle invasion, tumor recurrence, metastasis, present neu- rologic disease or history of neurologic disease, patient death, and failure to cooperate and follow-up for treat- ment. But the grade of leg jerking (a novel grade that we describe bettering comparison in different categories) effect was not significant (Table 1). The site of the ob- turator nerve was determined by nerve stimulation, ana- tomical landmarks, and ultrasonography. The obturator nerve is found by probing through the known location of the nerve(4). Inside a box were two similar folded papers (A and B), each patient took one of them. The nurse has written it down, and all have been done blindly and random- ly. When the operating room was reached, standard anesthesia monitors were used, and the patients were preloaded intravenously with 500 ml 0.9% normal sa- line. Spinal anesthesia was performed in both groups with a 25 G Quincke needle in the space L3-4 or L4-5 in a sitting position. After confirming the presence of clear flowing cerebro- spinal fluid in the syringe barrel, 10 mg of 0.5% bupiv- acaine was administered. The patients were in Trende- lenburg position for 5 or 10 minutes at an angle of 15 °. If the block of the sensory level was above the T10 level, the patients were placed in the lithotomy posi- tion, and the thulium laser or monopolar TURBT was performed. The thulium laser was used in the first group (16 pa- tients), while monopolar TURBT was performed in a blinded manner in the second group (19 patients). Clinical data, including age, gender, tumor features, op- eration duration, types of leg jerking, and some intraop- erative complications, were recorded. Leg jerking and period of the procedures were compared. Thulium laser was eradicated by the recruited device (Siemens Com- pany, Germany) with extension and power of 5 mm and 200j/sec. The bladder was half-filled during the proce- dure, and TURBT was started. The same surgeon did all procedures. Data analysis was performed among 35 cases, including 16 in Laser and 19 in the standard group. Data analysis was performed by SPSS (version 22.0) software [Sta- tistical Procedures for Social Sciences; Chicago, Illi- nois, USA]. Inter-group comparisons were performed using the One-Way Analysis test of variance or Inde- pendent-Sample-T test for continuous variables and Chi-Square and Fisher tests for categorical variables. P-values less than 0.05 were considered to be statisti- cally significant. RESULTS All 35 patients were randomized to receive the thulium laser (n = 16) or the monopolar TURBT (n = 19). Pa- tient and tumor features before surgeries were alike in both groups and are reported in Table 2. There were 28 male and seven female patients. All patients had suffi- cient specimens for making an accurate diagnosis, in- cluding tumor grading and staging. Of the 35 patients, 25 had low-grade tumors, and 10 had high-grade tumors (Table 2). The mean operation time was no difference between the two groups significantly (P > 0.05; Table 3). In four patients in the thulium, the laser group experienced intraoperative leg jerking, including 3 with horizontal leg jerking at the site without movement (Grade 1), 1 with horizontal and vertical leg jerking with movement (Grade 2), and no patient with horizontal and vertical leg jerking with movement from the location. In the monopolar TURBT group, 12 patients experienced intraoperative leg jerking, including 5 with horizontal leg jerking at the site without movement (Grade 1), 3 with horizontal and vertical leg jerking with movement (Grade 2), and 4 with horizontal and vertical leg jerk- ing with movement from location (P < 0.05; Table 3). There was no complication of bladder perforation and severe bleeding in the thulium laser group, but one pa- tient had bladder perforation, and one patient had severe bleeding during the monopolar TURBT (P > 0.05; Ta- ble 3). No mortality was reported during the operations. DISCUSSION Obturator nerve stimulation during TURBT under spi- nal anesthesia may lead to obturator reflex, adductor Table 1. Grade of Leg Jerking Grade 1 Horizontal leg jerking at site without movement Grade 2 Horizontal and vertical leg jerking with movement Grade 3 Horizontal and vertical leg jerking with movement from location Variable Thulium laser (n =16) Monopolar TURBT (n =19) Male 13 (81.3) 15 (78.9) Female 3 (18.8) 4 (21.1) Age, years 62.0 ± 6.9 (40-75) 64.0±7.1 (41-77) Tumor size, cm 3.3 ± 1.6 (1.5-5.0) 3.5 ± 1.1 (1.7-5.0) Tumor location Right side 9 (56.3) 10 (52.6) Left side 7 (43.8) 9 (47.4) Tumor grade Low grade 11 (68.8) 14 (73.7) High grade 5 (31.2) 5 (26.3) Data reported as n (percent) or mean±SD (range). Table 2. Demographic and tumor features in patients with non muscle-invasive bladder tumor, treated with thulium laser or monopolar TURBT. Obturator reflex in Laser vs. conventional TURT-Abediyarvandi et al. Vol 18 No 6 November-December 2021 689 contraction, and leg jerking with complications such as bladder perforation, bleeding more than incomplete tu- mor resection(4,8). Some studies report that the thulium laser is superior to TURBT(13). However, none of the TURBT side effects were seen in our patients in the la- ser group. Our result confirmed that the use of thulium laser would lead to higher efficacy than the monopolar TURBT method. Different modalities, such as partial filling of the bladder during TURBT, reduction of re- sectoscope current intensity, resecting the tumor on the thinner slices, utilization of bipolar or Laser resecto- scopes, and using general anesthesia and muscle relax- ants together, are used to avoid different complications during surgery to reduce the rate of jerking legs(14-16). Migliari et al. reported that Thulium laser could be the potential alternative to TURBT and nowadays is considered the standard for diagnosis and treatment of Non-muscle invasive bladder cancer (NMBIC)(17). In his study, the thullium laser provided a detailed report of neoplastic depth contamination, indicating the pos- sibility of a second resection within 90 days. Before delivery, all different parts of bladder cancer can be combined with thulium lasers, which has the advantage of monopolar energy, especially when the tumor is in the lateral wall of the bladder, the bladder dome, or the perimeatal region(17,18). The Nd: YAG does not significantly affect the treat- ment of lower urinary tract transitional cell carcinoma. Ho: YAG and Tm: YAG seem to offer alternatives in the treatment of bladder cancer, but to prove their potential effects in more significant prospective, ran- domized controlled studies with long-term follow-up should be done(19,20). Ozer et al.(21) showed that bipolar bladder tumor resection was not superior to monopolar resection significantly than an obstructive reflex and bladder perforation. However, we found a significant difference was also demonstrated by Balci et al.(22), stating that efficacy and safety of monopolar and bi- polar methods are comparable in patients with bladder tumors. Venkatramani and his colleagues reported that bipolar TURBT is not superior to monopolar resection in leg jerking, bladder perforation, and bleeding(23). This same result was also found in our research study. In our tertiary care center, a large number of patients are oper- ated on for bladder malignancies. Most of these patients are elderly with various comorbidities. Spinal anesthe- sia is preferred over general anesthesia in these patients. However, the ON stimulation during the procedure with subsequent obturator jerk makes spinal anesthesia less popular among our surgeons. H Liu has shown that the 2-micron laser resection method effectively reduces operative and postoperative complications compared to TURBT but has no other benefits in tumor recurrence. However, patients with multiple non-muscle-invasive bladder tumors were ran- domized to receive the TURBT or the 2-μm Laser in a non-blind clinical trial. At the same time, our study was designed as a blind randomized clinical trial(7). Moreover, Yunjin performed a systematic meta-analy- sis review and stated that laser techniques are practical, safe, and effective and provide an alternative treatment for non-muscle-invasive bladder tumors. Because some limitations cannot be met, well-designed RCTs are needed to confirm their results(20). Mario W. Kramer, in a systematic review, concluded that lasers are poten- tially useful options for conventional TURBTs, but sys- tematic evaluation using standard classification systems and well-designed RCTs are needed to compare results meaningfully(24). CONCLUSIONS Totally, according to the obtained results in the current study, the use of Thulium laser is a more feasible and effective method to prevent leg jerking in patients with a bladder tumor, and the use of this method is suggest- ed. However, further studies with a larger sample size Variable Thulium laser (n=16) Monopolar TURBT (n=19) P-value Operation duration 32.0 ± 13.5 (25-80) 34.0 ± 11.8 (28-82) P =. 64 Leg Jerking Grade Grade 1 3 (18.8) 5 (26.3) P = *.007 Grade 2 1 (6.2) 3 (15.8) Grade 3 0 (0) 4 (21.1) Total 4 (25) 12 (63.1) Complications Severe bleeding 0 (0) 1 (0.1) P =. 36 Bladder perforation 0 (0) 1 (0.1) P = .36 Incomplete Surgery 0 (0) 0 (0) P > 0.05 Table 3. Operative features of patients with non-muscle-invasive bladder tumor, treated with thulium laser or monopolar TURBT Data reported as n (percent) or mean ± SD (range). * P-value less than 0.05 is considered as the significantly meaningful one. Unclassified 690 Figure1. 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