UROLOGICAL ONCOLOGY Influences of Different Operative Methods on the Recurrence Rate of Non-Muscle-Invasive Bladder Cancer Shoubin Li#1, Yi Jia#1, Chunhong Yu2, Helong Xiao1, Liuxiong Guo1, Fuzhen Sun1, Dong Wei1, Panying Zhang1, Jingpo Li1,J unjiang Liu*1 Purpose: To compare the influence of three operative approaches [transurethral en bloc resection of bladder tumor by pin-shaped electrode (pin-ERBT), transurethral resection of bladder tumor (TURBT), and transurethral hol- mium laser resection of bladder tumor (HoLRBT)] on the recurrence rate of non-muscle-invasive bladder cancer (NMIBC) with low dimensions (i.e. diameter below 3 cm). Materials and Methods: A retrospective analysis was conducted for a total of 115 patients affected by solitary NMIBC, with a diameter < 3 cm, who were submitted to operation between March 2013 to May 2017. The patients were divided according to the operative method applied (pin-ERBT, TURBT, and HoLRBT groups, respectively). The 2-year recurrence rate was compared among the three groups, and multivariate Cox hazard model analysis was applied to analyze the influencing factor(s) for postoperative recurrence. Results: The 2-year recurrence rate was 10.0% in ERBT, 38.5% in TURBT and 40.0% in HoLRBT group, with a significant difference (P = 0.014). According to the Cox hazard model analysis, age (HR = 1.058, 95% CI: 1.019~1.098, P = 0.003), operative method (HR = 2.974,6.508, 95% CI: 0.862~10.255,1.657~25.566, P = 0.023), smoking (HR=2.399, 95% CI: 1.147~5.017, P = 0.020), and pathological grade (HR = 2.012,95% CI: 1.279~3.165, P = 0.002) were risk factors for postoperative recurrence of bladder cancer. Conclusion: Pin-ERBT can prominently decrease the postoperative recurrence rate of solitary NMIBC with a diameter < 3 cm. Keywords: ERBT; pin-shaped electrode; NMIBC; recurrence; TURBT; HoLRBT INTRODUCTION Bladder cancer (BC) is considered one of the com-mon malignant tumors of the urinary system. BC can be classified as non-muscle-invasive bladder cancer (NMIBC) and muscle-invasive bladder cancer (MIBC). Transurethral resection of bladder tumor (TURBT) is the most typical treatment for this pathological condi- tion. Still, TURBT has certain disadvantages, such as dissemination and seeding as well as incomplete resec- tion due to fragmentation of tumor tissues, which can potentially lead to a higher postoperative recurrence rate. Maurice and colleagues have shown that the post- operative recurrence rate of TURBT can be as high as 30-50%(1) As a novel operative methodology, en bloc resection of bladder tumor by pin-shaped electrode (pin-ERBT) can entirely promote the resection of the bladder tumor utilizing the distinctive features of a pin- shaped electrode, which possesses advantages such as clear layer, precise cleavage and accurate pathologi- cal stage after operation. Transurethral holmium laser resection of bladder tumor (HoLRBT) is another new procedure that enables a gradual or entire excision of the bladder tumor by laser-based energy.(2) Therefore, here we investigated the impact of these three operative methods on the postoperative recur- rence rate of BC. For this, their recurrence rates were 1Department of Urology, Hebei General Hospital, , Shijiazhuang, Hebei, China 2Department of Medical Checkup Centre, Hebei General Hospital,, Shijiazhuang, Hebei, China. # Equal Contributors and First Authors *Correspondence: Department of Urology, Hebei General Hospital, , Shijiazhuang, Hebei China, 050051, China Tel: +86 0311 85988751, E-mail: liujunjiang67@163.com Received February 2020 & Accepted October 2020 retrospectively reviewed, and Cox hazard model anal- ysis was performed to analyze the risk factors linked to the recurrence of solitary NMIBC, at the dimension of less than 3 cm. PATIENTS AND METHODS Study Population A total of 115 NMIBC patients who were treated with transurethral surgery for the first time in our hospital, between March 2013 and May 2017, were selected. Inclusion and exclusion criteria Inclusion criteria: ① Primary, solitary, and Ta stage bladder tumor with a maximum diameter less than 3cm. ② Treated by one of the three transurethral surgeries; ③ Recieved 1 year of standardized bladder perfusion treatment after operation, and regular reexamination of cystoscopy. ④ The surgeons had experience of TURBT over 10 years. Exclusion criteria: ①Recurrent bladder tumor. ②Benign or non-urothelial tumor pathological diagnosis. ③ Tumors which were multiple or with a diameter greater than or equal to 3cm; ④ patients with other tumors. The operation was performed by 3 senior consultants with rich experience in TURBT. Surgical technique The enrolled patients were divided into 3 groups ac- Urology Journal/Vol 18 No. 4/ July-August 2021/ pp. 411-416. [DOI: 10.22037/uj.v16i7.5965] cording to the operative methods, namely pin-ERBT (n = 30), TURBT (n = 65) and HoLRBT (n = 20) groups. Based on the WHO 2004 classification(3), tumors were classified into grade I (papillary urothelial neoplasm of low malignant potential), II (low-grade urothelial car- cinoma) and III (high-grade urothelial carcinoma). The baseline data of the patients are shown in Table 1. Their diagnosis was confirmed by ultrasonography, CT plain scan, and contrast-enhanced scan of the urinary system, as well as cystoscopy and tissue biopsy. The local Eth- ics Committee approved the use of patient data, and consent was obtained from all patients involved. Pin-ERBT group A tissue range of ~1 cm away from the basilar part of the tumor was initially marked with the pin-shaped electrode. Mucous, submucosa, and superficial muscu- lar layers were then cut open and gradually separated towards the basilar part of the bladder tumor, along with the superficial muscular layer, using the electrode. Thereafter, the whole tumor and basilar parts were fully dissociated and the supply vessels of the tumor were concomitantly coagulated. Isolated tumor tissues were further washed out using an irrigator or taken out with a retrieval basket. TURBT group The operation range was labeled at ~1 cm away from the tumor area using a looped electrode. Subsequent- ly, both tumor and peripheral mucosa were electrically resected from the crown of the tumor to the superficial muscular layer of the bladder. The resected tissues were then washed out using an irrigator. HoLRBT group An optical fiber (diameter =550 μm, laser energy =1.0- 2.0 J, frequency =15-20 Hz) was selected for a circular cutting of the muscular layer, along the periphery, at 1 cm away from the basilar region of the tumor. Cutting was done towards the tumor root until the intact tumor was excised. This procedure was performed under a di- rect light source. Tumor tissues were further washed out using an irrigator. Alternatively, tumors were removed using a retrieval basket. After each operative procedure, patients were given persistent bladder washout and postoperative indwell- ing of urethral catheter. Thereafter, intravesical instil- lation of pirarubicin or gemcitabine was performed. Patients were reexamined by cystoscopy once every 3 months after the operation, when the time to recurrence was eventually recorded. Each patient was followed up to 2 years or recurrence. The Median follow-up dura- tion in each group was 24 months. Statistical Analysis SPSS 21.0 was adopted for statistical data analysis. Data measurements were expressed as mean ± standard deviation ( ± s). Independent sample’s t-test was used for comparison between two groups. Alternatively, one- way analysis of variance was performed for compari- son among multiple groups. Categorical and count data were presented as n (%). The comparison of unordered categorical data between groups was subjected to χ2 test, while the comparison of ordered categorical data between two groups was examined by Mann-Whitney U test Kruskal-Wallis H test was utilized for compari- son among multiple groups. The cumulative recurrence rate at each time point was compared, among different operative approaches, using the Kaplan-Meier method. Cox hazard model analysis was applied to screen the risk factors for tumor recurrence. Statistical signifi- cance was defined by p < 0.05. RESULTS Clinical features of selected NMIBC patients are pre- sented in Table 1. Comparison of surgery information among distinct pa- tient groups As indicated in Table 2, no significant differences were observed in regard to sex, age, diabetes mellitus, and smoking among the patient groups. The differences in the lesion size, pathological grade, and bladder lesion position were not statistically significant when compar- ing each group of patients. Also, we observed that the operation time was longer in pin-ERBT group than that in TURBT and HoLRBT groups. This difference was statistically significant (P = 0.007). According to the results of χ2 test, however, no statistically significant differences among the groups were observed in the type of anesthesia used (P = 0.888) and the category of per- fused drug (P = 0.991). Comparison of recurrence rate in patients from distinct groups The pin-ERBT group had a remarkably lower recur- rence rate than TURBT and HoLRBT groups after 24 months of operation (P = 0.014) (Table 3). Analysis of risk factors for recurrence in distinct patient groups Based on the results of univariate analysis, the recur- rence was not correlated with the perfused drug (P = 0.544) and lesion position (P = 0.723). Nevertheless, the recurrence rate had associations with factors in- cluding sex (P = 0.024), age (P ＜0.001), smoking (P ＜0.001), pathological grade (P ＜0.001), type of an- Table 1. Statistics of clinical features among the BC patient pop- ulation.re results CLINICAL FEATURE STATISTICAL RESULT Sex Male 93 (80.9) Female 22 (19.1) Age (years old) 64.46±11.91 (33.0-88.0) Lesion size (cm) 1.86±0.73 (0.2-3.0) Type of anesthesia General anesthesia 74 (64.3) Spinal anesthesia 41 (35.7) Operation time (hrs) 1.53±0.31 (0.8-3.0) Pathological grade Papillary urothelial neoplasms 43 (37.4) of low malignant potential Low-grade urothelial carcinoma 37 (32.2) High-grade urothelial carcinoma 35 (30.4) Perfused drug Pirarubicin 103 (89.6) Gemcitabine 12 (10.4) Diabetes mellitus 20 (17.4) Smoking 35 (30.4) Recurrence rate at 12 months 11 (9.6) Recurrence rate at 24 months 36 (31.3) Operative method Pin-ERBT 30 (26.1) TURBT 65 (56.5) HoLRBT 20 (17.4) Lesion position Lateral wall 72 (62.6) Neck 8 (7.0) Anterior wall 25 (21.7) Trigone 10 (8.7) Operation techniques and recurrence in NMIBC-Li et al. Vol 18 No 4 July-August 2021 412 Urological Oncology 413 esthesia (P =0.018) and operative method (P = 0.044) (Table 4). In the multivariate Cox hazard model analysis, the re- currence was taken as the dependent variable, the fol- low-up time was taken as the time variable, and the indexes with statistical significance in the univariate analysis, including gender, age, anesthesia mode, patho- logical level, smoking, operation mode were regarded as independent variables. The assignment of each vari- able is shown in Table 4. The results indicated that age (P = 0.003), operative method (P = 0.023), smoking (P = 0.020) and pathological grade (P = 0.002) were the risk factors for the recurrence among the patients. Comparison of cumulative recurrence rate among groups The 24-month cumulative recurrence rates in the TUR- BT and HoLRBT groups were similarly higher than that in the pin-ERBT group, and this difference was statisti- cally significant (P = 0.021) (Figure 1). DISCUSSION Bladder cancer is a relatively high incidence rate of can- cer. Accurate diagnosis requires cystoscopy and patho- logical diagnosis. Special types of bladder tumors, such as bladder small cell carcinoma, are difficult to diag- nose and need to be confirmed by immunohistochemis- try(4).TURBT is a commonly used operative method for bladder cancer. Still, 36-51% of the TURBT-derived specimens lack muscular layer tissues(5), limiting the determination of the pathological stage(13). Besides, the Table 2. Description of biopsy needle tip cultures and blood cultures of febrile patients Pin-ERBT n=30 TURBT n=65 HoLRBT n=20 P- value Sex Male 24 (80.0) 55 (84.6) 14 (70.0) 0.344 Female 6 (20.0) 10 (15.4) 6 (30.0) Age; Mean ± SD, year 63.23 ± 10.39 66.23 ± 11.86 60.55±13.51 0.141 Diabetes 4 (13.3) 14 (21.5) 2 (10.0) 0.390 Smoking 9 (30.0) 20 (30.8) 6 (30.0) 0.996 Lesion size (cm) Mean ± SD, 1.94±0.64 1.88 ± 0.75 1.66 ± 0.76 0.374 Pathological grade (%)a I 13 (43.3) 21 (32.3) 9 (45.0) 0.680 II 9 (30.0) 24 (36.9) 4 (20.0) III 8 (26.7) 20 (30.8) 7 (35.0) Lesion position(%) Lateral wall 23 (76.7) 38 (58.5) 11 (55.0) 0.555 Neck 1 (3.3) 5 (7.7) 2 (10.0) Anterior wall 4 (13.3) 17 (26.2) 4 (20.0) Trigone 2 (6.7) 5 (7.7) 3 (15.0) Operation time (h) 1.68 ± 0.32 1.49 ± 0.27b 1.44 ± 0.34 0.007 Type of anesthesia (%) General anesthesia 20 (66.7) 42 (64.6) 12 (60.0) 0.888 Spinal anesthesia 10 (33.3) 23 (35.4) 8 (40.0) Perfused drug (%) Pirarubicin 27 (90.0) 58 (89.2) 18 (90.0) 0.991 Gemcitabine 3 (10.0) 7 (10.8) 2 (10.0) Note a: I: papillary urothelial neoplasm of low malignant potential, II: low-grade urothelial carcinoma, III: high-grade urothelial carci- noma. Noteb: bp < 0.05 vs. pin-ERBT group. Figure 1. Comparison of cumulative recurrence rate at 24 months after operation among groups. Operation techniques and recurrence in NMIBC-Li et al. tumor residual rate along the basilar region can be up to 30-44% after TURBT(6). Second transurethral resection may remove the tumor more thoroughly, but there are also controversies. Some scholars think that in patients with single, small T1 and/or high-grade tumors, second- ary TURBT is not closely related to tumor residual and disease deterioration(7). At the same time, the incidence of obturator reflex in TURBT is high, and there is a risk of bladder perforation(8). It has been denoted that, in the TURBT group,~70% of specimens contain muscular layer tissues, while entire tumor specimens containing muscular layer tissues can be obtained in both HoLR- BT and ERBT groups(9). The cauterization of the tumor tissues by TURBT can alter the tissue morphology, so that intact specimens containing a muscular layer can- not be acquired. Some studies have indicated that tumor staging can be clinically underestimated up to 49% of the patients(10). Engilbertsson and colleagues(11) have identified the conditions of tumor cells in the circulat- ing blood of 16 patients before and during TURBT. In this case, tumor cells could be observed in 7 patients, from which 6 (86%) had a much higher number of tu- mor cells during operation, suggesting that tumor cells may enter the circulation system during TURBT, there- fore increasing the risk of tumor metastasis and tumor recurrence. The recurrence rate of BC is typically high, but relat- ed data can vary in the current literature. For instance, Hurle and colleagues have reported that the recurrence rate of BC is 15% by a 2-year follow-up after en bloc resection by pin-shaped electrode(12). Based on laser en bloc resection, Muto and colleagues have found a re- currence rate of ~14.5% at 16 months after postopera- tive follow-up(13). Liu and colleagues also compared the postoperative recurrence rate between patients who were submitted to laser en bloc resection (n = 64) ver- sus traditional TURBT (n = 56)(14). According to their results, the recurrence rates were 10.9%, 19.5% and 31.3% after 1, 2, and 3 years of en bloc resection, ver- sus 10.7%, 22.9%, and 33.9%, after traditional electro resection, respectively. Still, no significant differences were detected between the two groups. In terms of the risk factors related to the recurrence of BC, Rink and colleagues revealed that an active smok- ing history was an independent risk factor for recur- rence after BC surgery in males(15). Lu and colleagues found that the recurrence rate was positively correlated with the pathological grade of the tumor(16). Moreover, Koumpan and colleagues have shown that patients un- dergoing combined spinal-epidural analgesia have a lower recurrence rate than those undergoing general anesthesia(17). In this case, it appears that the volatile an- esthetics used during general anesthesia may stimulate the production of hypoxia-inducible factor 1 (HIF-1), thus activating the proliferation of tumor cells. In this study, we did not find that the choice of intravesical in- stillation drugs is related to tumor recurrence, and the relevant literature also shows that the difference be- tween the choice of pirarubicin and gemcitabine is not a risk factor for tumor recurrence, but the incidence of bladder irritation symptoms after gemcitabine selection is slightly lower than that of pirarubicin(18) . In the present study, the recurrence rate in the pin-ER- BT group after 2 years of operation was markedly low- er than in the TURBT and HoLRBT groups, which is consistent with some previous studies(19,20). Intriguingly, Chen’(21) s reports have shown similar postoperative re- currence rates on both ERBT and HoLRBT but, in the present study, the HoLRBT group exhibited a distinct- ly higher long-term (2-year) recurrence rate than the Table 3. Comparison of recurrence rate among patients receiving different operative methods. Group n Recurrence rate at 24 months Pin-ERBT 30 3 (10.0) TURBT 65 25 (38.5)a HoLRBT 20 8 (40.0)a χ2 - 8.583 p - 0.014 Note: ap < 0.05 vs. pin-ERBT group. un-adjusted effect size (Univariate) adjusted effect size (Multivariate) Factor Waldχ2 P HR(95% CI) Variable Waldχ2 P HR(95% CI) Recurrence Yes =1, No = 0 Gender 5.107 0.024 2.228(1.112~4.464) Male=1, female=2 0.006 0.937 1.031(0.486~2.189) Age 12.382 0.000 1.064(1.028~1.101) Numerical type 8.864 0.003 1.058(1.019~1.098) Lesion size 0.118 0.731 0.922(0.580~1.465) - - - Anesthesia method 5.598 0.018 2.206(1.145~4.248) Spinal anesthesia =1, 0.778 0.378 1.404(0.661~2.98) general anesthesia =2 Operation time 0.962 0.327 0.562(0.178~1.778) - - - Pathological gradea 15.259 0.000 2.417(1.552~3.764) Grade I =1, grade II =2, 9.152 0.002 2.012(1.279~3.165) grade III =3 Perfused drug 0.367 0.544 0.694(0.213~2.262) - - - Diabetes 0.515 0.473 0.708(0.275~1.820) - - - Smoking 8.508 0.004 2.648(1.376~5.095) Yes=1, No=0 5.407 0.02 2.399(1.147~5.017) Operative method Pin-ERBT 6.227 0.044 1 Pin-shaped electrode =1 7.533 0.023 1 TURBT 5.828 0.016 4.375(1.320~14.499) electric resection =2 2.977 0.084 2.974(0.862~10.255) HoLRBT 5.381 0.020 4.816(1.276~18.173) holmium laser =3 7.199 0.007 6.508(1.657~25.566) Lesion position Lateral wall 1.326 0.723 - - - Neck 0.353 0.552 1.445(0.429~4.868) - - - Anterior wall 1.128 0.288 1.509(0.706~3.225) - - - Trigone 0.001 0.976 1.019(0.303~3.430) - - - Notea: I: papillary urothelial neoplasm of low malignant potential, II: low-grade urothelial carcinoma, III: high-grade urothelial carcino- ma. Table 4. Univariate COX analysis and Multivariate COX regression analysis results. Operation techniques and recurrence in NMIBC-Li et al. Vol 18 No 4 July-August 2021 414 Urological Oncology 415 pin-ERBT group. There are some possible explanations for this kind of contradicting results. First, the holmium laser may simultaneously cleave and vaporize proper- ties, so it cannot clearly recognize anatomical layers when compared with the pin-shaped electrode. Second, the holmium laser does not generally achieve a satisfac- tory resection effect on tumors located in sharp angles, such as the bladder dome and the anterior bladder wall, due to the straight optical fibers. Third, it is difficult to control the depth of cutting promoted by the holmium laser, which can easily cause bladder perforation(22). According to the results of multivariate Cox hazard model regression analysis, clinical features including age, operative method, smoking and pathological grade were the risk factors for the recurrence of BC. The oper- ative method served as an influencing factor with statis- tical significance, indicating that operative factors can affect the recurrence rate, besides the biological charac- teristics of the tumor. The pin-shaped electrode is typically slim in shape and able to flexibly rotated and to bluntly dissect, allowing a precise cleavage of the tissue. Therefore, it can accu- rately resect tumors at distinct sites of the bladder by means of 360° rotation of endoscopic sheath. Some ad- vantages can be highlighted for this kind of operation: (i) tumors can be cut and isolated along the muscular layer, so the resection is more precise and the exact pathological stage can be defined; (ii) labeling of the cutting range before cleavage as well as partial blockage of blood supply can decrease the probability of metas- tasis and recurrence induced by blood-borne dissemina- tion; (iii) specimens can be removed entirely, reducing the implantation and recurrence rates of BC. In contrast, pin-ERBT also has a few limitations. This technique, for instance, is not suitable for extensive NMIBC tu- mors. Indeed, in the case of tumors larger than 3 cm in diameter, the resected specimens cannot be removed completely. Therefore, some in-depth optimization for en bloc resection of larger tumors(i.e. diameter less than 3 cm) will be further required. Compared with TURBT and HoLRBT, pin-ERBT is characterized by fewer complications, higher efficien- cy, thorough tumor enucleation, lower recurrence rate, and easier handling. As such, this operative method is worthy of clinical popularization and application. Nev- ertheless, there were some limitations in this study. Firstly, the sample size for this research was small, so the elaboration of more long-term, large-sample and multi-center prospective studies will be needed to con- firm our data. Secondly, only the patients with solitary tumors with a diameter over 3 cm were analyzed, so the operative efficacy using multiple ranges of large tumors should be further verified. ACKNOWLEDGEMENTS The authors would like to express their gratitude to Ed- itSprings (https://www.editsprings.com/) for the expert linguistic services provided. Yi-Jia espeically wishes to thank Xi-Lin,whose long term company have given he powerful spiritual support over the past times. CONFLICT OF INTEREST The authors report no conflict of interest. REFERENCES 1. Maurice MJ, Vricella GJ, MacLennan G, Buehner P, Ponsky LE. Endoscopic snare resection of bladder tumors: evaluation of an alternative technique for bladder tumor resection. J. Endourol. 2012;26:614-7. 2. Bai Y, Liu L, Yuan H, et al. Safety and efficacy of transurethral laser therapy for bladder cancer: a systematic review and meta- analysis. World J. Surg. Oncol. 2014;12:301. 3. Lopez-Beltran A, Montironi R. Non-invasive urothelial neoplasms: according to the most recent WHO classification. Eur. Urol. 2004;46:170-6. 4. Nayeri RK, Sadri M, Shahrokh H, et al. Small Cell Carcinoma of Bladder; Still A Diagnostic and Therapeutic Challenge: Seven Years of Experience and Follow-up in A Referral Center. Urol J. 2020. 5. DUTTA SC, SMITH JA, SHAPPELL SB, COFFEY CS, CHANG SS, COOKSON MS. Clinical under staging of high risk nonmuscle invasive urothelial carcinoma treated with radical cystectomy. J. Urol. 2001;166:490-3. 6. Suer E, Hamidi N, Gokce MI, et al. Significance of second transurethral resection on patient outcomes in muscle-invasive bladder cancer patients treated with bladder- preserving multimodal therapy. World J. Urol. 2016;34:847-51. 7. Ayati M, Amini E, Damavand RS, et al. Second Transurethral Resection of Bladder Tumor: Is it Necessary in All T1 and/or High- Grade Tumors? Urol J. 2019;16:152-6. 8. Dagli R, Dadali M, Emir L, Bagbanci S, Ates H. Comparison of Classic and Inguinal Obturator Nerve Blocks Applied for Preventing Adductor Muscle Contractions in Bladder Tumor Surgeries: A Prospective Randomized Trial. Urol J. 2019;16:62-6. 9. Chen J, Zhao Y, Wang S, et al. Green‐ light laser en bloc resection for primary non‐muscle‐invasive bladder tumor versus transurethral electroresection: a prospective, nonrandomized two‐center trial with 36‐month follow‐up. Lasers Surg. Med. 2016;48:859-65. 10. BRAUERS A, BUETTNER R, Jakse G. Second resection and prognosis of primary high risk superficial bladder cancer: is cystectomy often too early? J. Urol. 2001;165:808-10. 11. Engilbertsson H, Aaltonen KE, Björnsson S, et al. Transurethral bladder tumor resection can cause seeding of cancer cells into the bloodstream. J. Urol. 2015;193:53-7. 12. Hurle R, Lazzeri M, Colombo P, Buffi N, Guazzoni G. “En Bloc” Resection of NMIBC: a Prospective Single Centre Study. Urology. 2016;90. 13. Muto G, Collura D, Giacobbe A, D'Urso L, Castelli E. Thulium:yttrium-aluminum– garnet Laser for En Bloc Resection of Bladder Cancer: Clinical and Histopathologic Advantages. Urology. 2014;83. 14. Liu H, Wu J, Xue S, et al. Comparison of the safety and efficacy of conventional monopolar and 2-micron laser transurethral resection in the management of multiple nonmuscle- invasive bladder cancer. J. Int. Med. Res. Operation techniques and recurrence in NMIBC-Li et al. 2013;41:984-92. 15. Rink M, Furberg H, Zabor EC, et al. Impact of smoking and smoking cessation on oncologic outcomes in primary non–muscle-invasive bladder cancer. Eur. Urol. 2013;63:724-32. 16. Ðug H, Jagodić S, Ahmetović-Ðug J, Selimović Z, Sulejmanović A. Predicting recurrence of non-muscle-invasive bladder cancer after transurethral resection. Medicinski Glasnik. 2016;13. 17. Koumpan Y, Jaeger M, Mizubuti GB, et al. Spinal anesthesia is associated with lower recurrence rates after resection of nonmuscle invasive bladder cancer. J. Urol. 2018;199:940-6. 18. Yang H, Li JY, Tan W, Wang J. Clinical study of bladder infusion with different drugs to prevent postoperative recurrence of bladder tumor patients. PLA Journal of Medicine. 2016. 19. Sureka SK, Agarwal V, Agnihotri S, Kapoor R, Srivastava A, Mandhani A. Is en-bloc transurethral resection of bladder tumor for non-muscle invasive bladder carcinoma better than conventional technique in terms of recurrence and progression?: A prospective study. Indian journal of urology: IJU: journal of the Urological Society of India. 2014;30:144. 20. Zhong C, Guo S, Tang Y, Xia S. Clinical observation on 2 micron laser for non- muscle-invasive bladder tumor treatment: single-center experience. World J. Urol.. 2010;28:157-61. 21. Chen SY FF, Du Y,Du LD. Comparison of efficacy and safety of transurethral pin-shaped electrode en bloc resection of bladder tumor and transurethral holmium laser resection of bladder tumor for non muscle invasive bladder cancer. Journal of China Capital Medical University. 2014;v.39:138-42. 22. Greskovich III FJ, von Eschenbach AC. Bladder perforation resulting from the use of the neodymium: YAG laser. Lasers Surg. Med. 1991;11:5-7. Operation techniques and recurrence in NMIBC-Li et al. Vol 18 No 4 July-August 2021 416