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Safety and Efficacy of En Bloc Transurethral Resection With 1.9 µm Vela Laser for Treatment of Non–Muscle-invasive Bladder Cancer
Accepted Manuscript Title: Safety and Efficacy of en Bloc Transurethral Resection with 1.9Μm Vela Laser for Treatment of Non-Muscle-Invasive Bladder Cancer Author: Hao Xu, Jun Ma, Zhong Chen, Jun Yang, Huixin Yuan, Tao Wang, Jihong Liu, Weimin Yang, Zhangqun Ye PII: DOI: Reference:
S0090-4295(17)31231-1 https://doi.org/10.1016/j.urology.2017.11.030 URL 20782
To appear in:
Urology
Received date: Accepted date:
21-6-2017 18-11-2017
Please cite this article as: Hao Xu, Jun Ma, Zhong Chen, Jun Yang, Huixin Yuan, Tao Wang, Jihong Liu, Weimin Yang, Zhangqun Ye, Safety and Efficacy of en Bloc Transurethral Resection with 1.9Μm Vela Laser for Treatment of Non-Muscle-Invasive Bladder Cancer, Urology (2017), https://doi.org/10.1016/j.urology.2017.11.030. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Title: Safety and efficacy of en bloc transurethral resection with 1.9μm Vela laser for treatment of non-muscle-invasive bladder cancer
Authors Hao Xu ([email protected]) 1. Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, China. 2. Institute of Urology Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, China.
Jun Ma ([email protected]) 1. Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, China. 2. Institute of Urology Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, China.
Zhong Chen ([email protected]) 1. Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, China. 2. Institute of Urology Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, China.
Jun Yang ([email protected]) 1. Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, China.
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2. Institute of Urology Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, China.
Huixin Yuan ([email protected]) 1. Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, China. 2. Institute of Urology Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, China.
Tao Wang ([email protected]) 1. Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, China. 2. Institute of Urology Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, China.
Jihong Liu ([email protected]) 1. Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, China. 2. Institute of Urology Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, China.
Weimin Yang ([email protected]) 1. Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, China. 2. Institute of Urology Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, China.
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Zhangqun Ye ([email protected]) 1. Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, China. 2. Institute of Urology Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, China. Corresponding author Zhong Chen Address: Department of Urology Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology Wuhan, Hubei China Phone:
+86-27-83663460
Fax:
+86-27-83663460
Email:
[email protected]
Running title 1.9μm Vela laser for non-muscle-invasive bladder cancer
Word count for the Abstract 247
Word count for the manuscript 2549
Acknowledgements We want to especially acknowledge all the participants in this study.
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Financial Disclosure The work was supported by grants National Natural Science Foundation of China, Project (No.81372759).
Conflicts of interest: none
Key words Bladder cancer, Vela laser, en bloc transurethral resection
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Abstract Objectives To evaluate the safety and efficacy of 1.9μm Vela laser in treating of primary nonmuscle-invasive bladder cancer. Methods The data of the non-muscle invasive bladder cancer patients treated either by en bloc transurethral resection with 1.9μm Vela laser (n=26) or conventional transurethral resection of bladder tumor (n=44) was analyzed retrospectively. The pre-operative characteristics and intra-operative complications were compared in the two groups. Results Patients who treated by 1.9μm Vela laser got a higher rate to obtain specimens meeting the requirements of pathological assessment for tumor staging comparing with the patients treated by conventional transurethral resection of bladder tumor. There were no obturator nerve reflex and bladder perforation occurred during surgery in the 1.9μm Vela laser group. However, 7 patients in conventional transurethral resection of bladder tumor group encountered obturator nerve reflex, and 3 of them encountered bladder perforation (p<0.05). There were no significant differences among the two groups in operative duration, and transfusion rate. Patients in the 1.9μm Vela laser groups had shorter postoperative continuous bladder irrigation time than that in the conventional transurethral resection of bladder tumor group. There was no significant difference in the overall recurrence rate among the two groups during the follow-up periods. Conclusions En bloc transurethral resection with 1.9μm Vela laser in treatment of non-muscleinvasive bladder cancer demonstrate an advantage over conventional transurethral resection of bladder tumor in reducing intra-operative complications, improving the quality of the specimens admitted for pathological assessment, and shortening the duration of postoperative continuous bladder irrigation.
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Introduction Bladder cancer (BCa) is the seventh most commonly malignancy tumor in the male population worldwide. The age-standardised incidence rate (per 100 000 person-years) is 9.0 for men and 2.2 for women 1. Approximately, 75% of patients with BCa present with a disease invaded to the mucosa (stage Ta, CIS) or submucosa (stage T1), which are known as non-muscle-invasive bladder cancer (NMIBC) 2. Transurethral resection of bladder tumor (TURBT) is still considered as a “golden standard” surgical procedure for the NMIBC patients. A complete and correct resection of the tumor is essential to achieve a good prognosis 1. The conventional TURBT is performed using a monopolar or bipolar electrocautery resecting loop. However, some recognized risks, such as perforation of the bladder, bleeding, and obturator nerve reflex, are encountered during the conventional surgical procedures, especially when the lesions were located in the lateral bladder wall or around ureter orifice 3. In recent years, the application of lasers in urological surgeries has undergone great development. The main mechanism of laser-tissue interaction was elucidated by many different authors4,5. Firstly, the center part of the tissue exposed to laser radiation absorbs most of the laser energy and was heated to a temperature as high as 90 to 100℃，which caused tissue vaporization. Then, the tissue adjacent to the vaporized part was heated to a lower temperature at 60 to 80℃, enough for coagulating the proteinic composition of tissues (protein denaturation), which formed the “coagulation layer” in the tissue. Beneath the coagulation layer, edema develops due to the tissue temperature is only around 45 to 50℃ at which enzymatic changes occur. Different kinds of lasers, including potassium-titanyl-phosphate laser, holmium laser, 2micrometer continuous wave thulium laser and 120W high performance system green light laser, et al, have been used in the transurethral resection of bladder tumor. All of these lasers have been reported as safe and feasible procedure providing an alternative for the NMIBC patients 2,3,6-8. 1.9μm Vela laser is the second generation of thulium laser. Compared with other lasers with different wavelength, the absorption rate of the 1.9μm Vela laser is higher in water, and the cutting capacity is stronger while heat damage is less. In China, only a few clinical centers performed the en bloc transurethral
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resection of NMIBC with lasers. As far as we know, only one article in Chinese reported the using of 1.9μm laser in the transurethral resection of NMIBC. In the current study, we evaluated the safety and efficacy of en bloc transurethral resection of NMIBC with 1.9μm Vela laser in our hospital while comparing with conventional TURBT.
Materials and Methods From June 2014 to December 2015, patients who treated either by conventional TURBT or 1.9μm Vela laser for bladder cancer at Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology were retrospectively analyzed. The inclusion criteria for this investigation included：Primary, not the recurrent bladder cancer, with the diameter of the tumor less than 4.5 cm, without upper urinary tract tumor, and the pathological result was non-muscle invasive bladder cancer without carcinoma in situ. A total of 93 patients were diagnosed as primary bladder cancer and treated either by conventional TURBT or 1.9μm Vela laser at our department from June 2014 to December 2015 . In the 93 patients, 30 of them were treated by 1.9μm Vela laser and 63 of them by conventional TURBT. All of the patients who treated by 1.9μm Vela laser got specimens which met the requirements of pathological assessment for tumor staging. However, 16 of the 63 patients who underwent conventional TURBT could not define the tumor stage in the pathological investigation because the electric cauterization destroying the bottom of the specimens in the conventional TURBT and these patients were excluded from this study (Typical images are shown in Supplementary Figure 1). That is to say, patients treated by 1.9μm Vela laser got a higher rate (100% vs 74.6%, p=0.04) of high quality specimens which met the requirements of pathological assessment for tumor staging comparing with the patients treated by conventional TURBT. After the pathological assessment, 4 patients who treated by 1.9μm Vela laser and 3 patients who underwent conventional TURBT were excluded from this study because the pathological results after operation revealed the cancer (T2) had invaded into the muscular part of the bladder. At last, only 70 patients (26 patients in 1.9μm Vela laser group and 44 patients in conventional TURBT group) met the study criteria and were enrolled in this study (Supplementary Figure 2).
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The detail history of all patients has been obtained preoperatively. Ultrasonography, intravenous urography, computerized tomography of the urinary system and cystoscopy have been routinely performed to exclude upper urinary tract tumors, and to determine the location, number, and size of the tumors as well as to evaluate the clinical stage of tumor pre-operatively. The advantages and disadvantages of the two surgery procedures were informed to all of the patients pre-operatively. The patients could choose either of the two surgical strategies with written informed consent. All the operations were performed with standard procedures to get a comparable result. All Vela laser surgeries were performed by one Professor and all the conventional TURBT were performed by the other skilled Professors in our department. The patients were in the lithotomy position and combined intravenous and inhalation anesthesia was administered before the surgery begun. The bladder was fully examined and the tumor location, size, appearance, number and adjacent mucosa were carefully checked and recorded before the surgery begun. For the Vela laser group, en bloc transurethral resection was performed using a 22F continuous-flow cystoscope with 30◦ lens and 1.9μm Vela laser System (Vela XL) made by StarMedTec in Germany with a power set at 30W. The detail of the Vela laser procedure is showed following. Firstly, we performed the circumferential incision with the 1.9μm Vela laser starting from about 5 mm away from the edge of the tumor. Then the incision was progressively deepened into the deep muscular layer of the bladder under the tumor by the 1.9μm Vela laser. After that sharp separation was performed using the 1.9μm Vela laser between the muscular layer and serosa of the bladder to peel the tissue block (Figure 1). Then, the tissue block was rinsed out of the cystoscope sheath naturally or taken out by electrocautery resecting loop. After that, the size of the tumor was confirmed by measuring the pathology specimen. For the conventional TURBT group, traditional piece-by-piece resection to the muscle layer was performed. The resection was executed 1.5 cm away around the visible tumor edge and down to the deep muscular layer of the bladder wall in both of the two groups. The Pathological analysis of each specimen was performed by standard protocol in the Department of Pathology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology. The operative time in this study which included the time for preparation of the appliance
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before the operation, the time for resection, the time for taking out the specimen from the bladder and the time for dwelling catheterization in this study was faithfully recorded. The data regarding the preoperative characteristics and intraoperative complications such as obturator nerve reflex and bladder perforation, and postoperative conditions such as continuous bladder irrigation time, catheterization time and tumor recurrence in the two groups were recorded. The bladder perforation was diagnosed by the cystoscope during the surgery procedure. If the bladder perforation was not very certain during the operation, cystography was performed after the surgery to confirm it. After surgical treatment, 30mg Pirarubicin, a common chemotherapeutic drug for bladder cancer, was used for intravesical instillation therapy within 24 hours after surgery for the first time. After that, Pirarubicin was also given as intravesical instillation treatment weekly for 8 weeks, and then once every month for 10 months. For postoperative surveillance, ultrasonography and cystoscopy were performed every 3 months to monitor the recurrence of bladder cancer. The follow-up period in this study was 1 ~ 2 years. SPSS19.0 software was applied for statistical analysis. Continuous data were analyzed using the mean ± SD and compared by non-parametric t test. Categorical variables were compared using the chi-square test or Fisher’s exact test. P<0.05 was considered to be statistically significant.
Results The characteristics of the patients and tumors of the two groups before surgery are list in Table 1. No significant differences in the sex, age, mean tumor number, mean tumor max size, tumor location, tumor stage and grade of the two groups were observed (P>0.05). The intraoperative and postoperative characteristics of Vela laser group and conventional TURBT group are showed in Table 2. There were no obturator nerve reflex and bladder perforation occurred during surgery in the Vela laser group (Supplementary
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Figure 3). However, 7 of 44 patients in the conventional TURBT group experienced obturator nerve reflex. Moreover, 3 patients encountered bladder perforation (Grade I) as a result of obturator nerve reflux in conventional TURBT group. All these complications reported in this study were classified as Grade I according to the Clavien Classification of Surgical Complications. The mean duration time (min) of the operations in the two groups showed no significant difference (58.9±33.5: 74.0±36.6 minutes in Vela laser group vs. TURBT group, p=0.08). However, the mean postoperative continuous bladder irrigation time (h) in the Vela laser group is significantly shorter than that in the TURBT group (29.1±11.4: 41.6±24.4 h in Vela laser group vs. conventional TURBT group, p=0.005). Furthermore, we found that there were no patient in both of the two groups required blood transfusion and none showed any evidence of TUR syndrome. No significant difference in postoperative catheterization and hospitalization time were observed in the two groups. All patients were followed up for 12 to 24 months after surgery. There was no significant difference in the recurrence rate during the follow-up periods in Vela laser group and conventional TURBT group, which were 4 in 26 and 12 in 44 (p=0.38), respectively.
Discussion Currently, TURBT followed by intravesical therapy is still considered to be a primary approach to the management of non–muscle invasive bladder cancer (NMIBC). TURBT is recommended as the “gold standard” for the initial diagnosis and treatment of NMIBC by the European Association of Urology (EAU) guidelines 1. However, the efficacy of conventional TURBT as well as the intra- and postoperative complications, largely depend on the resection techniques and experience of individual surgeons
9,10
. For
example, relatively shallow depth resection can cause an incomplete resection and such patients need re-TURBT 11. Moreover, electric cauterization in the conventional TURBT could destroy the bottom tissue of the specimens which may lead to insufficient muscle in the specimens for the assignment of T category in the pathologic investigation. In our retrospective study, 16 of the 63 patients who underwent conventional TURBT could not define the tumor stage in the pathological investigation
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because the electric cauterization destroying the muscle of the tissues. On the other hand, deeper resection may accompany by a higher risk of bladder perforation and severe bleeding. Furthermore, when the lesion was located in the lateral bladder wall, the obturator nerve would be stimulated by the current flow in high probability, so the obturator spasm and leg jerk would occur and bladder perforation sometimes occurred 12
.
The use of lasers such as potassium-titanyl-phosphate laser, holmium laser, 2micrometer continuous wave thulium laser, 120W high performance system green light laser for treating NMIBC have been confirmed to be safe and effective in many studies 2,3,6-8
. Comparing with conventional TURBT, these lasers have many advantages in
reducing intra- and postoperative complications and postoperative bladder irrigation, and shortening postoperative catheterization and hospitalization time. The 1.9μm Vela laser, which has a higher absorption rate in water, stronger cutting capacity, and less heat damage compared with other lasers with different wavelength, had been used in the treatment of digestive tract big polyps 13. However, there was no literature in English report the utilization of 1.9μm Vela laser in the treatment of bladder tumor. In author’s department, 1.9μm Vela laser was firstly used for treating NMIBC in June 2014. Compared with conventional TURBT, we observed at least three advantages while using the 1.9μm Vela laser for the en bloc transurethral resection of NMIBC in our study. Firstly, 1.9μm Vela laser has a short wavelength and the tissue penetration depth of the laser is only 0.2 mm which results in a more precision cutting in the 1.9μm Vela laser procedure than in conventional TURBT. That is very critical to avoid bladder perforation and reduce the muscle destroying in the specimens (Supplementary Figure 1). As a result, the quality of specimens of the patients who treated by 1.9μm Vela laser is higher. In our study, all of the specimens of the patients treated by 1.9μm Vela laser met the requirements of pathological assessment for tumor staging. Secondly, as all of the lasers, 1.9μm Vela laser was produced by laser system without any current flow going through the human body. So the obturator nerve reflex will not occur when the laser was used for the resection of NMIBC when the tumor located in the lateral wall of the bladder. In our study, no obturator nerve reflex occurred in the
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Vela laser group. As a result, no bladder perforation during surgery was occurred during surgery in the 1.9μm Vela laser group. Thirdly, many articles reported that the laser treatment can reduce the postoperative catheterization and hospitalization time and the possibility of postoperative bladder irrigation compared with conventional TURBT. In our study, the mean postoperative continuous bladder irrigation time in the Vela laser group is significantly shorter than that in the TURBT group in Vela laser group. However, as this study is a pilot study, we performed postoperative continuous bladder irrigation for each patient who underwent endoscopic treatment of bladder tumor to reduce the potential risk of possible bleeding. If there was no sign of bladder bleeding after the surgery, the continuous bladder irrigation will be stop timely. In this study, the time of postoperative continuous bladder irrigation in the 1.9μm Vela laser group was significantly shorter than that in the conventional TURBT group. That suggested the postoperative bleeding in the Vela laser group was less than that in conventional TURBT group. For similar reasons, we intend to indwell the catheter for a longer period of time in our patients in order to monitor the possible delayed hemorrhage and avoid delayed bladder perforation after surgery in our clinical practice. As a result, the postoperative catheterization and hospitalization time of the 1.9μm Vela laser group was overestimate. Those were the reasons why there was no statistically significant difference in postoperative catheter time and hospital stay in the two groups in this study. There were several factors may contribute to the recurrence of the tumor following transurethral resection including tumor multicentricity, incomplete tumor resection, and intra-operative dissemination of tumor cells 14. During the conventional TURBT procedure, tumor cells may seed into the bladder mucosa which leads to the recurrence in situ or ectopic site of the bladder 15-17. However, according to the mechanism of lasertissue interaction, there was a “coagulation layer” beneath the laser vaporized part of the tissues 5. Thus, the possibility of tumor cells seeded into the bladder mucosa in situ was extremely low. By the way, during the en bloc transurethral resection with laser procedure, the tumors were cut out in its entirety from the periphery and bottom of the tumor. In theory, no tumor cells should seed into the washing fluid. According to the
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EAU Guidelines on Non-Muscle-invasive Urothelial Carcinoma of the Bladder, immediate single instillation and further chemotherapy instillations after SI both can reduce recurrences. So, after the surgical treatment, 30mg Pirarubicin was used for intravesical instillation therapy in all of our patients to reduce the recurrences. However, the recurrence rate in the Vela laser group demonstrated no statistically significant difference as compared with that in conventional TURBT group in this study. Similar result was found in other studies which aimed to investigate the safety and efficacy of other kinds of lasers in treating NMIBC 18,19. This finding should reinforced by a longer follow-up period and larger numbers of patients in the future study.
Conclusions In conclusion, our results suggested that use of the 1.9μm Vela laser for en bloc transurethral resection of NMIBC appears to be a safer technique than conventional TRUBT, with less peri-operative complications. This pilot study provided the necessary preliminarily data for the future study about the 1.9μm Vela laser for en bloc transurethral resection of NMIBC. The recurrence rate was similar compared to conventional TURBT 1~2 years after the surgery in this short-term preliminarily research. The finding of our study should be strengthened in the future study by longer follow-up time and larger sample size of patients.
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Abbreviations BCa = Bladder cancer NMIBC = Non-muscle-invasive bladder cancer TURBT = Transurethral resection of bladder tumor CIS = Carcinoma in situ
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Babjuk M, Bohle A, Burger M, Capoun O, Cohen D, Comperat EM, Hernandez V, Kaasinen E, Palou J, Roupret M et al.: EAU Guidelines on Non-Muscle-invasive Urothelial Carcinoma of the Bladder: Update 2016. Eur Urol, 2016. Burger M, Catto JW, Dalbagni G, Grossman HB, Herr H, Karakiewicz P, Kassouf W, Kiemeney LA, La Vecchia C, Shariat S et al.: Epidemiology and risk factors of urothelial bladder cancer. Eur Urol. 63: 234-41, 2013. Tao W, Yang D, Shan Y, Xue B, Sun C, Zang Y and Zhang Y: Safety and efficacy of 120W high performance system greenlight laser vaporization for non-muscle-invasive bladder cancer. J Xray Sci Technol. 21: 30916, 2013. Knappe V, Frank F and Rohde E: Principles of lasers and biophotonic effects. Photomed Laser Surg. 22: 411-7, 2004. Liang JH, Pan YL, Kang J and Qi J: Influence of irrigation on incision and coagulation of 2.0-mum continuous-wave laser: an ex vivo study. Surg Laparosc Endosc Percutan Tech. 22: e122-5, 2012. Gao X, Ren S, Xu C and Sun Y: Thulium laser resection via a flexible cystoscope for recurrent non-muscleinvasive bladder cancer: initial clinical experience. BJU Int. 102: 1115-8, 2008. Xishuang S, Deyong Y, Xiangyu C, Tao J, Quanlin L, Hongwei G, Jibin Y, Dongjun W, Zhongzhou H, Jianbo W et al.: Comparing the safety and efficiency of conventional monopolar, plasmakinetic, and holmium laser transurethral resection of primary non-muscle invasive bladder cancer. J Endourol. 24: 69-73, 2010. Liu H, Xue S, Ruan Y, Sun X, Han B and Xia S: 2-micrometer continuous wave laser treatment for multiple non-muscle-invasive bladder cancer with intravesical instillation of epirubicin. Lasers Surg Med. 43: 15-20, 2011. Daneshmand S: The value of extended transurethral resection of bladder tumour (TURBT) in the treatment of bladder cancer. BJU Int. 110: E80, 2012. Brausi M, Witjes JA, Lamm D, Persad R, Palou J, Colombel M, Buckley R, Soloway M, Akaza H and Bohle A: A review of current guidelines and best practice recommendations for the management of nonmuscle invasive bladder cancer by the International Bladder Cancer Group. J Urol. 186: 2158-67, 2011. Yucel M, Hatipoglu NK, Atakanli C, Yalcinkaya S, Dedekarginoglu G, Saracoglu U and Aras E: Is repeat transurethral resection effective and necessary in patients with T1 bladder carcinoma? Urol Int. 85: 27680, 2010. Yang D, Xue B, Zang Y, Liu X, Zhu J, Zhou Y and Shan Y: Efficacy and safety of potassium-titanyl- phosphate laser vaporization for clinically non-muscle invasive bladder cancer. Urol J. 11: 1258-63, 2014. Li K, Hu G, Xu M, Lu L, Wan R and Wang X: [Comparison of 1.9 microm Vela Laser versus high-frequency electronic knife in the treatment of digestive tract big polyps]. Zhonghua Yi Xue Za Zhi. 94: 3349-51, 2014. Tsivian A, Shtricker A and Sidi AA: Simultaneous transurethral resection of bladder tumor and benign prostatic hyperplasia: hazardous or a safe timesaver? J Urol. 170: 2241-3, 2003. Pode D, Alon Y, Horowitz AT, Vlodavsky I and Biran S: The mechanism of human bladder tumor implantation in an in vitro model. J Urol. 136: 482-6, 1986. Soloway MS and Masters S: Urothelial susceptibility to tumor cell implantation: influence of cauterization. Cancer. 46: 1158-63, 1980. Soloway MS, Nissenkorn I and McCallum L: Urothelial susceptibility to tumor cell implantation: comparison of cauterization with N-methyl-N-nitrosourea. Urology. 21: 159-61, 1983. Xu Y, Guan W, Chen W, Xie C, Ouyang Y, Wu Y and Liu C: Comparing the treatment outcomes of potassium-titanyl-phosphate laser vaporization and transurethral electroresection for primary nonmuscleinvasive bladder cancer: A prospective, randomized study. Lasers Surg Med. 47: 306-11, 2015. Kramer MW, Bach T, Wolters M, Imkamp F, Gross AJ, Kuczyk MA, Merseburger AS and Herrmann TR: Current evidence for transurethral laser therapy of non-muscle invasive bladder cancer. World J Urol. 29: 433-42, 2011.
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Figure 1. Legend A. Circumferential incision of the tumor base. B. The surgical wound in the bladder after the bladder cancer was removed by 1.9μm Vela laser. C. The bladder cancer sample which was removed by 1.9μm Vela laser.
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Supplementary Figure 1. Legend A. The pathological result of one of the specimen cutting by conventional TURBT. The black arrow shows the muscle of the specimen was destroyed by the electric cauterization. B. The pathological result of one of the specimen cutting by 1.9μm Vela laser. The muscle of the specimen is clearly showed.
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Supplementary Figure 2. Legend Flow diagram of the 93 participants.
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Supplementary Figure 3. Legend The cystogram image of one of the patients treated by bloc transurethral resection with 1.9μm Vela laser. The red arrow shows the position where the tumor was removed. No contrast medium extravasation was found in the X-ray.
Table 1. Patient and Tumor Characteristics Vela laser group(n=26)
TURBT group(n=44)
P value
Male
24(92.3%)
35(79.5%)
0.14
Female
2(7.7%)
9(20.5%)
55.9±11.1
59.7±10.9
0.17
Mean tumor number
1.7±1.3
1.8±1.0
0.81
Mean Tumor max size (cm)
2.3±1.0
2.2±1.0
0.68
≤3 cm
21(80.8%）
36（81.8%）
0.58
3-4.5 cm
5（19.2%）
8（18.1%）
Single
15(57.7%)
22(50.0%)
Multiple
11(42.3%)
22(50.0%)
Lateral
21(80.8%)
30(68.2%)
Other
5(19.2%)
14(31.8%)
Ta
10
25
T1
12
16
PUNLMP
4
3
LOW
14
28
High
8
13
Variable Sex
Age, Mean ± SD (year)
Tumor max size
Tumor multiplicity
Location
Stage
Grade (WHO2004)
0.35
0.28
0.24
0.46
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Abbreviations: TURBT, transurethral resection of bladder tumor; PUNLMP, papillary urothelial neoplasms of low malignant potential; WHO, World Health Organization.
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Table 2. Intra- and postoperative characteristics of 1.9μm Vela laser group vs. conventional TURBT group Vela laser group(n=26)
TURBT group(n=44)
P value
58.9±33.5
74.0±36.6
0.08
Obturator nerve reflex
0
7
0.04*
Transfusion
0
0
-
TUR syndrome
0
0
-
Bladder perforation
0
3
0.3
Duration of continuous postoperative bladder irrigation (h)
29.1±11.4
41.6±24.4
0.005*
Catheterization time (d)
5.2±1.7
5.6±2.0
0.38
Hospitalization time (d）
5.8±1.3
6.4±2.9
0.31
3
5
0.63
Variables Operation time (min)
Recurrence
Abbreviations: TURBT, transurethral resection of bladder tumor. TUR, transurethral resection. Data presented as number of patients, otherwise noted. *Statistically significant.
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S0090-4295(17)31231-1 https://doi.org/10.1016/j.urology.2017.11.030 URL 20782
To appear in:
Urology
Received date: Accepted date:
21-6-2017 18-11-2017
Please cite this article as: Hao Xu, Jun Ma, Zhong Chen, Jun Yang, Huixin Yuan, Tao Wang, Jihong Liu, Weimin Yang, Zhangqun Ye, Safety and Efficacy of en Bloc Transurethral Resection with 1.9Μm Vela Laser for Treatment of Non-Muscle-Invasive Bladder Cancer, Urology (2017), https://doi.org/10.1016/j.urology.2017.11.030. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Title: Safety and efficacy of en bloc transurethral resection with 1.9μm Vela laser for treatment of non-muscle-invasive bladder cancer
Authors Hao Xu ([email protected]) 1. Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, China. 2. Institute of Urology Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, China.
Jun Ma ([email protected]) 1. Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, China. 2. Institute of Urology Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, China.
Zhong Chen ([email protected]) 1. Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, China. 2. Institute of Urology Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, China.
Jun Yang ([email protected]) 1. Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, China.
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2. Institute of Urology Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, China.
Huixin Yuan ([email protected]) 1. Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, China. 2. Institute of Urology Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, China.
Tao Wang ([email protected]) 1. Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, China. 2. Institute of Urology Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, China.
Jihong Liu ([email protected]) 1. Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, China. 2. Institute of Urology Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, China.
Weimin Yang ([email protected]) 1. Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, China. 2. Institute of Urology Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, China.
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Zhangqun Ye ([email protected]) 1. Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, China. 2. Institute of Urology Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, China. Corresponding author Zhong Chen Address: Department of Urology Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology Wuhan, Hubei China Phone:
+86-27-83663460
Fax:
+86-27-83663460
Email:
[email protected]
Running title 1.9μm Vela laser for non-muscle-invasive bladder cancer
Word count for the Abstract 247
Word count for the manuscript 2549
Acknowledgements We want to especially acknowledge all the participants in this study.
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Financial Disclosure The work was supported by grants National Natural Science Foundation of China, Project (No.81372759).
Conflicts of interest: none
Key words Bladder cancer, Vela laser, en bloc transurethral resection
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Abstract Objectives To evaluate the safety and efficacy of 1.9μm Vela laser in treating of primary nonmuscle-invasive bladder cancer. Methods The data of the non-muscle invasive bladder cancer patients treated either by en bloc transurethral resection with 1.9μm Vela laser (n=26) or conventional transurethral resection of bladder tumor (n=44) was analyzed retrospectively. The pre-operative characteristics and intra-operative complications were compared in the two groups. Results Patients who treated by 1.9μm Vela laser got a higher rate to obtain specimens meeting the requirements of pathological assessment for tumor staging comparing with the patients treated by conventional transurethral resection of bladder tumor. There were no obturator nerve reflex and bladder perforation occurred during surgery in the 1.9μm Vela laser group. However, 7 patients in conventional transurethral resection of bladder tumor group encountered obturator nerve reflex, and 3 of them encountered bladder perforation (p<0.05). There were no significant differences among the two groups in operative duration, and transfusion rate. Patients in the 1.9μm Vela laser groups had shorter postoperative continuous bladder irrigation time than that in the conventional transurethral resection of bladder tumor group. There was no significant difference in the overall recurrence rate among the two groups during the follow-up periods. Conclusions En bloc transurethral resection with 1.9μm Vela laser in treatment of non-muscleinvasive bladder cancer demonstrate an advantage over conventional transurethral resection of bladder tumor in reducing intra-operative complications, improving the quality of the specimens admitted for pathological assessment, and shortening the duration of postoperative continuous bladder irrigation.
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Introduction Bladder cancer (BCa) is the seventh most commonly malignancy tumor in the male population worldwide. The age-standardised incidence rate (per 100 000 person-years) is 9.0 for men and 2.2 for women 1. Approximately, 75% of patients with BCa present with a disease invaded to the mucosa (stage Ta, CIS) or submucosa (stage T1), which are known as non-muscle-invasive bladder cancer (NMIBC) 2. Transurethral resection of bladder tumor (TURBT) is still considered as a “golden standard” surgical procedure for the NMIBC patients. A complete and correct resection of the tumor is essential to achieve a good prognosis 1. The conventional TURBT is performed using a monopolar or bipolar electrocautery resecting loop. However, some recognized risks, such as perforation of the bladder, bleeding, and obturator nerve reflex, are encountered during the conventional surgical procedures, especially when the lesions were located in the lateral bladder wall or around ureter orifice 3. In recent years, the application of lasers in urological surgeries has undergone great development. The main mechanism of laser-tissue interaction was elucidated by many different authors4,5. Firstly, the center part of the tissue exposed to laser radiation absorbs most of the laser energy and was heated to a temperature as high as 90 to 100℃，which caused tissue vaporization. Then, the tissue adjacent to the vaporized part was heated to a lower temperature at 60 to 80℃, enough for coagulating the proteinic composition of tissues (protein denaturation), which formed the “coagulation layer” in the tissue. Beneath the coagulation layer, edema develops due to the tissue temperature is only around 45 to 50℃ at which enzymatic changes occur. Different kinds of lasers, including potassium-titanyl-phosphate laser, holmium laser, 2micrometer continuous wave thulium laser and 120W high performance system green light laser, et al, have been used in the transurethral resection of bladder tumor. All of these lasers have been reported as safe and feasible procedure providing an alternative for the NMIBC patients 2,3,6-8. 1.9μm Vela laser is the second generation of thulium laser. Compared with other lasers with different wavelength, the absorption rate of the 1.9μm Vela laser is higher in water, and the cutting capacity is stronger while heat damage is less. In China, only a few clinical centers performed the en bloc transurethral
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resection of NMIBC with lasers. As far as we know, only one article in Chinese reported the using of 1.9μm laser in the transurethral resection of NMIBC. In the current study, we evaluated the safety and efficacy of en bloc transurethral resection of NMIBC with 1.9μm Vela laser in our hospital while comparing with conventional TURBT.
Materials and Methods From June 2014 to December 2015, patients who treated either by conventional TURBT or 1.9μm Vela laser for bladder cancer at Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology were retrospectively analyzed. The inclusion criteria for this investigation included：Primary, not the recurrent bladder cancer, with the diameter of the tumor less than 4.5 cm, without upper urinary tract tumor, and the pathological result was non-muscle invasive bladder cancer without carcinoma in situ. A total of 93 patients were diagnosed as primary bladder cancer and treated either by conventional TURBT or 1.9μm Vela laser at our department from June 2014 to December 2015 . In the 93 patients, 30 of them were treated by 1.9μm Vela laser and 63 of them by conventional TURBT. All of the patients who treated by 1.9μm Vela laser got specimens which met the requirements of pathological assessment for tumor staging. However, 16 of the 63 patients who underwent conventional TURBT could not define the tumor stage in the pathological investigation because the electric cauterization destroying the bottom of the specimens in the conventional TURBT and these patients were excluded from this study (Typical images are shown in Supplementary Figure 1). That is to say, patients treated by 1.9μm Vela laser got a higher rate (100% vs 74.6%, p=0.04) of high quality specimens which met the requirements of pathological assessment for tumor staging comparing with the patients treated by conventional TURBT. After the pathological assessment, 4 patients who treated by 1.9μm Vela laser and 3 patients who underwent conventional TURBT were excluded from this study because the pathological results after operation revealed the cancer (T2) had invaded into the muscular part of the bladder. At last, only 70 patients (26 patients in 1.9μm Vela laser group and 44 patients in conventional TURBT group) met the study criteria and were enrolled in this study (Supplementary Figure 2).
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The detail history of all patients has been obtained preoperatively. Ultrasonography, intravenous urography, computerized tomography of the urinary system and cystoscopy have been routinely performed to exclude upper urinary tract tumors, and to determine the location, number, and size of the tumors as well as to evaluate the clinical stage of tumor pre-operatively. The advantages and disadvantages of the two surgery procedures were informed to all of the patients pre-operatively. The patients could choose either of the two surgical strategies with written informed consent. All the operations were performed with standard procedures to get a comparable result. All Vela laser surgeries were performed by one Professor and all the conventional TURBT were performed by the other skilled Professors in our department. The patients were in the lithotomy position and combined intravenous and inhalation anesthesia was administered before the surgery begun. The bladder was fully examined and the tumor location, size, appearance, number and adjacent mucosa were carefully checked and recorded before the surgery begun. For the Vela laser group, en bloc transurethral resection was performed using a 22F continuous-flow cystoscope with 30◦ lens and 1.9μm Vela laser System (Vela XL) made by StarMedTec in Germany with a power set at 30W. The detail of the Vela laser procedure is showed following. Firstly, we performed the circumferential incision with the 1.9μm Vela laser starting from about 5 mm away from the edge of the tumor. Then the incision was progressively deepened into the deep muscular layer of the bladder under the tumor by the 1.9μm Vela laser. After that sharp separation was performed using the 1.9μm Vela laser between the muscular layer and serosa of the bladder to peel the tissue block (Figure 1). Then, the tissue block was rinsed out of the cystoscope sheath naturally or taken out by electrocautery resecting loop. After that, the size of the tumor was confirmed by measuring the pathology specimen. For the conventional TURBT group, traditional piece-by-piece resection to the muscle layer was performed. The resection was executed 1.5 cm away around the visible tumor edge and down to the deep muscular layer of the bladder wall in both of the two groups. The Pathological analysis of each specimen was performed by standard protocol in the Department of Pathology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology. The operative time in this study which included the time for preparation of the appliance
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before the operation, the time for resection, the time for taking out the specimen from the bladder and the time for dwelling catheterization in this study was faithfully recorded. The data regarding the preoperative characteristics and intraoperative complications such as obturator nerve reflex and bladder perforation, and postoperative conditions such as continuous bladder irrigation time, catheterization time and tumor recurrence in the two groups were recorded. The bladder perforation was diagnosed by the cystoscope during the surgery procedure. If the bladder perforation was not very certain during the operation, cystography was performed after the surgery to confirm it. After surgical treatment, 30mg Pirarubicin, a common chemotherapeutic drug for bladder cancer, was used for intravesical instillation therapy within 24 hours after surgery for the first time. After that, Pirarubicin was also given as intravesical instillation treatment weekly for 8 weeks, and then once every month for 10 months. For postoperative surveillance, ultrasonography and cystoscopy were performed every 3 months to monitor the recurrence of bladder cancer. The follow-up period in this study was 1 ~ 2 years. SPSS19.0 software was applied for statistical analysis. Continuous data were analyzed using the mean ± SD and compared by non-parametric t test. Categorical variables were compared using the chi-square test or Fisher’s exact test. P<0.05 was considered to be statistically significant.
Results The characteristics of the patients and tumors of the two groups before surgery are list in Table 1. No significant differences in the sex, age, mean tumor number, mean tumor max size, tumor location, tumor stage and grade of the two groups were observed (P>0.05). The intraoperative and postoperative characteristics of Vela laser group and conventional TURBT group are showed in Table 2. There were no obturator nerve reflex and bladder perforation occurred during surgery in the Vela laser group (Supplementary
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Figure 3). However, 7 of 44 patients in the conventional TURBT group experienced obturator nerve reflex. Moreover, 3 patients encountered bladder perforation (Grade I) as a result of obturator nerve reflux in conventional TURBT group. All these complications reported in this study were classified as Grade I according to the Clavien Classification of Surgical Complications. The mean duration time (min) of the operations in the two groups showed no significant difference (58.9±33.5: 74.0±36.6 minutes in Vela laser group vs. TURBT group, p=0.08). However, the mean postoperative continuous bladder irrigation time (h) in the Vela laser group is significantly shorter than that in the TURBT group (29.1±11.4: 41.6±24.4 h in Vela laser group vs. conventional TURBT group, p=0.005). Furthermore, we found that there were no patient in both of the two groups required blood transfusion and none showed any evidence of TUR syndrome. No significant difference in postoperative catheterization and hospitalization time were observed in the two groups. All patients were followed up for 12 to 24 months after surgery. There was no significant difference in the recurrence rate during the follow-up periods in Vela laser group and conventional TURBT group, which were 4 in 26 and 12 in 44 (p=0.38), respectively.
Discussion Currently, TURBT followed by intravesical therapy is still considered to be a primary approach to the management of non–muscle invasive bladder cancer (NMIBC). TURBT is recommended as the “gold standard” for the initial diagnosis and treatment of NMIBC by the European Association of Urology (EAU) guidelines 1. However, the efficacy of conventional TURBT as well as the intra- and postoperative complications, largely depend on the resection techniques and experience of individual surgeons
9,10
. For
example, relatively shallow depth resection can cause an incomplete resection and such patients need re-TURBT 11. Moreover, electric cauterization in the conventional TURBT could destroy the bottom tissue of the specimens which may lead to insufficient muscle in the specimens for the assignment of T category in the pathologic investigation. In our retrospective study, 16 of the 63 patients who underwent conventional TURBT could not define the tumor stage in the pathological investigation
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because the electric cauterization destroying the muscle of the tissues. On the other hand, deeper resection may accompany by a higher risk of bladder perforation and severe bleeding. Furthermore, when the lesion was located in the lateral bladder wall, the obturator nerve would be stimulated by the current flow in high probability, so the obturator spasm and leg jerk would occur and bladder perforation sometimes occurred 12
.
The use of lasers such as potassium-titanyl-phosphate laser, holmium laser, 2micrometer continuous wave thulium laser, 120W high performance system green light laser for treating NMIBC have been confirmed to be safe and effective in many studies 2,3,6-8
. Comparing with conventional TURBT, these lasers have many advantages in
reducing intra- and postoperative complications and postoperative bladder irrigation, and shortening postoperative catheterization and hospitalization time. The 1.9μm Vela laser, which has a higher absorption rate in water, stronger cutting capacity, and less heat damage compared with other lasers with different wavelength, had been used in the treatment of digestive tract big polyps 13. However, there was no literature in English report the utilization of 1.9μm Vela laser in the treatment of bladder tumor. In author’s department, 1.9μm Vela laser was firstly used for treating NMIBC in June 2014. Compared with conventional TURBT, we observed at least three advantages while using the 1.9μm Vela laser for the en bloc transurethral resection of NMIBC in our study. Firstly, 1.9μm Vela laser has a short wavelength and the tissue penetration depth of the laser is only 0.2 mm which results in a more precision cutting in the 1.9μm Vela laser procedure than in conventional TURBT. That is very critical to avoid bladder perforation and reduce the muscle destroying in the specimens (Supplementary Figure 1). As a result, the quality of specimens of the patients who treated by 1.9μm Vela laser is higher. In our study, all of the specimens of the patients treated by 1.9μm Vela laser met the requirements of pathological assessment for tumor staging. Secondly, as all of the lasers, 1.9μm Vela laser was produced by laser system without any current flow going through the human body. So the obturator nerve reflex will not occur when the laser was used for the resection of NMIBC when the tumor located in the lateral wall of the bladder. In our study, no obturator nerve reflex occurred in the
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Vela laser group. As a result, no bladder perforation during surgery was occurred during surgery in the 1.9μm Vela laser group. Thirdly, many articles reported that the laser treatment can reduce the postoperative catheterization and hospitalization time and the possibility of postoperative bladder irrigation compared with conventional TURBT. In our study, the mean postoperative continuous bladder irrigation time in the Vela laser group is significantly shorter than that in the TURBT group in Vela laser group. However, as this study is a pilot study, we performed postoperative continuous bladder irrigation for each patient who underwent endoscopic treatment of bladder tumor to reduce the potential risk of possible bleeding. If there was no sign of bladder bleeding after the surgery, the continuous bladder irrigation will be stop timely. In this study, the time of postoperative continuous bladder irrigation in the 1.9μm Vela laser group was significantly shorter than that in the conventional TURBT group. That suggested the postoperative bleeding in the Vela laser group was less than that in conventional TURBT group. For similar reasons, we intend to indwell the catheter for a longer period of time in our patients in order to monitor the possible delayed hemorrhage and avoid delayed bladder perforation after surgery in our clinical practice. As a result, the postoperative catheterization and hospitalization time of the 1.9μm Vela laser group was overestimate. Those were the reasons why there was no statistically significant difference in postoperative catheter time and hospital stay in the two groups in this study. There were several factors may contribute to the recurrence of the tumor following transurethral resection including tumor multicentricity, incomplete tumor resection, and intra-operative dissemination of tumor cells 14. During the conventional TURBT procedure, tumor cells may seed into the bladder mucosa which leads to the recurrence in situ or ectopic site of the bladder 15-17. However, according to the mechanism of lasertissue interaction, there was a “coagulation layer” beneath the laser vaporized part of the tissues 5. Thus, the possibility of tumor cells seeded into the bladder mucosa in situ was extremely low. By the way, during the en bloc transurethral resection with laser procedure, the tumors were cut out in its entirety from the periphery and bottom of the tumor. In theory, no tumor cells should seed into the washing fluid. According to the
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EAU Guidelines on Non-Muscle-invasive Urothelial Carcinoma of the Bladder, immediate single instillation and further chemotherapy instillations after SI both can reduce recurrences. So, after the surgical treatment, 30mg Pirarubicin was used for intravesical instillation therapy in all of our patients to reduce the recurrences. However, the recurrence rate in the Vela laser group demonstrated no statistically significant difference as compared with that in conventional TURBT group in this study. Similar result was found in other studies which aimed to investigate the safety and efficacy of other kinds of lasers in treating NMIBC 18,19. This finding should reinforced by a longer follow-up period and larger numbers of patients in the future study.
Conclusions In conclusion, our results suggested that use of the 1.9μm Vela laser for en bloc transurethral resection of NMIBC appears to be a safer technique than conventional TRUBT, with less peri-operative complications. This pilot study provided the necessary preliminarily data for the future study about the 1.9μm Vela laser for en bloc transurethral resection of NMIBC. The recurrence rate was similar compared to conventional TURBT 1~2 years after the surgery in this short-term preliminarily research. The finding of our study should be strengthened in the future study by longer follow-up time and larger sample size of patients.
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Abbreviations BCa = Bladder cancer NMIBC = Non-muscle-invasive bladder cancer TURBT = Transurethral resection of bladder tumor CIS = Carcinoma in situ
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Figure 1. Legend A. Circumferential incision of the tumor base. B. The surgical wound in the bladder after the bladder cancer was removed by 1.9μm Vela laser. C. The bladder cancer sample which was removed by 1.9μm Vela laser.
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Supplementary Figure 1. Legend A. The pathological result of one of the specimen cutting by conventional TURBT. The black arrow shows the muscle of the specimen was destroyed by the electric cauterization. B. The pathological result of one of the specimen cutting by 1.9μm Vela laser. The muscle of the specimen is clearly showed.
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Supplementary Figure 2. Legend Flow diagram of the 93 participants.
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Supplementary Figure 3. Legend The cystogram image of one of the patients treated by bloc transurethral resection with 1.9μm Vela laser. The red arrow shows the position where the tumor was removed. No contrast medium extravasation was found in the X-ray.
Table 1. Patient and Tumor Characteristics Vela laser group(n=26)
TURBT group(n=44)
P value
Male
24(92.3%)
35(79.5%)
0.14
Female
2(7.7%)
9(20.5%)
55.9±11.1
59.7±10.9
0.17
Mean tumor number
1.7±1.3
1.8±1.0
0.81
Mean Tumor max size (cm)
2.3±1.0
2.2±1.0
0.68
≤3 cm
21(80.8%）
36（81.8%）
0.58
3-4.5 cm
5（19.2%）
8（18.1%）
Single
15(57.7%)
22(50.0%)
Multiple
11(42.3%)
22(50.0%)
Lateral
21(80.8%)
30(68.2%)
Other
5(19.2%)
14(31.8%)
Ta
10
25
T1
12
16
PUNLMP
4
3
LOW
14
28
High
8
13
Variable Sex
Age, Mean ± SD (year)
Tumor max size
Tumor multiplicity
Location
Stage
Grade (WHO2004)
0.35
0.28
0.24
0.46
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Abbreviations: TURBT, transurethral resection of bladder tumor; PUNLMP, papillary urothelial neoplasms of low malignant potential; WHO, World Health Organization.
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Table 2. Intra- and postoperative characteristics of 1.9μm Vela laser group vs. conventional TURBT group Vela laser group(n=26)
TURBT group(n=44)
P value
58.9±33.5
74.0±36.6
0.08
Obturator nerve reflex
0
7
0.04*
Transfusion
0
0
-
TUR syndrome
0
0
-
Bladder perforation
0
3
0.3
Duration of continuous postoperative bladder irrigation (h)
29.1±11.4
41.6±24.4
0.005*
Catheterization time (d)
5.2±1.7
5.6±2.0
0.38
Hospitalization time (d）
5.8±1.3
6.4±2.9
0.31
3
5
0.63
Variables Operation time (min)
Recurrence
Abbreviations: TURBT, transurethral resection of bladder tumor. TUR, transurethral resection. Data presented as number of patients, otherwise noted. *Statistically significant.
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