- Email: [email protected]
A Pilot Study of Vela Laser for En Bloc Resection of Papillary Bladder Cancer
Accepted Manuscript A pilot study of Vela laser for en bloc resection of papillary bladder cancer Zhensheng Zhang, Shuxiong Zeng, Junjie Zhao, Xin Lu, Weidong Xu, Chong Ma, Yang Wang, Xin Chen, Gaozhen Jia, Yinghao Sun, Chuanliang Xu PII:
S1558-7673(16)30150-1
DOI:
10.1016/j.clgc.2016.06.004
Reference:
CLGC 633
To appear in:
Clinical Genitourinary Cancer
Received Date: 20 November 2015 Accepted Date: 5 June 2016
Please cite this article as: Zhang Z, Zeng S, Zhao J, Lu X, Xu W, Ma C, Wang Y, Chen X, Jia G, Sun Y, Xu C, A pilot study of Vela laser for en bloc resection of papillary bladder cancer, Clinical Genitourinary Cancer (2016), doi: 10.1016/j.clgc.2016.06.004. 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.
ACCEPTED MANUSCRIPT Title: A pilot study of Vela laser for en bloc resection of papillary bladder cancer Authors: Zhensheng Zhang1#, Shuxiong Zeng1#, Junjie Zhao1, Xin Lu1,
RI PT
Weidong Xu1, Chong Ma1, Yang Wang2, Xin Chen1, Gaozhen Jia1，Yinghao Sun1*, Chuanliang Xu1*
Short Title： ：Vela laser for en bloc bladder tumor resection
SC
Key Words： ：Thulium laser, bladder cancer, en bloc resection, TURBT
Financial Disclosures: The authors declare that they have no relevant
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financial interests.
Funding Support: This study did not receive any funding support. #
Zhensheng Zhang, Shuxiong Zeng contributed equally to the paper and are
cofirst authors 1
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From the Department of Urology, Changhai Hospital, Second Military Medical
University, Shanghai, P. R. China 2
EP
From the Department of Pathology, Changhai Hospital, Second Military
Medical University, Shanghai, P. R. China *
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Correspondence: Yinghao Sun, Ph.D., M.D., Chuanliang Xu Ph.D., M.D.
Department of Urology, Changhai Hospital, Second Military Medical University, 168
Changhai
Rd,
Shanghai
200433,
P.
R.
[email protected]; [email protected]
China.
E-mail:
ACCEPTED MANUSCRIPT Microabstract Transurethral resection of bladder tumor is associated with perioperative or postoperative complications, and “incise and scatter” procedure contradicts the
RI PT
basic oncologic principles. The present study introduced Vela laser, a new kind of thulium laser with 1.94μm wavelength, for en bloc resection of bladder tumor. The
feasible and safe for patients with bladder tumor.
Objectives
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Abstract
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pilot experience found Vela laser could preserve the muscle layer and was effective,
To evaluate the safety and efficacy of Vela laser for en bloc resection of
papillary bladder tumor.
Materials and methods From January 2013 to August 2014, 38 patients were
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treated by Vela laser en bloc resection with 26F continuous flow resectoscope or 18 F flexible cystoscope. Randomly cold-forceps biopsy samples were also performed. Total operation time, pathologic result, intraoperative or postoperative complications
The average total operation time was 23 minutes, All the tumors were en
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Results
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were recorded. Each patient was followed at least one year.
bloc removed successfully, with 2 cases located at the bladder dome requiring flexible cystoscope for better management. No complication occurred within or after operation. All of resected tumor was intact with detrusor muscle layer and architecture for pathologic evaluation. One patient with T2b tumor performed laparoscopic cystectomy 1 week after initial surgery. At a median follow-up of 21.8 month, the recurrence rate at 12th month was 8/37 (21.6%).
ACCEPTED MANUSCRIPT Conclusion
Vela laser was an effective, feasible and safe thulium laser for en bloc
bladder tumor resection, it was associated with negligible complication and can bring accurate pathologic evaluation. Vela laser can serve as an alternative treatment for
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EP
TE D
M AN U
SC
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non-muscle invasive bladder cancer or infiltrating tumor diagnosis.
ACCEPTED MANUSCRIPT Introduction Bladder cancer is one of the most common tumors in genitourinary system. It was estimated to occur in more than 74,690 new cases and lead to 15,580 deaths in 2014
RI PT
in the USA1. Moreover, bladder cancer has the largest financial burden per patient among all kinds of malignant tumors, this is due to the high frequency of recurrence and progression which thus need lifelong monitoring and repetitive treatment 2.
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Most bladder cancers (75%) are non-muscle invasive bladder cancer (NMIBC) and
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transurethral resection of bladder tumor (TURBT) is regarded as the standard diagnostic and therapeutic method3. However, this technique may be associated with significant complications, e.g. bleeding, bladder perforation, obturator nerve reflex and even bladder explosion4. Furthermore, the main disadvantage of TURBT is the
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“incise and scatter” procedure contradicts the basic oncologic principles and herein may cause implantation of exfoliated cancer cells and difficulty for pathologic evaluation5-7.
EP
In order to tackle the problems, mentioned above, related to TURBT, several new
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kinds of laser-based surgical procedures have emerged . Staehler et al.8 first utilize neodymium (Nd): yttriumaluminum- garnet (YAG) laser device in bladder cancer treatment in 1978. By far, holmium (Ho) YAG, potassium-titanyl-phosphate (KTP) green-light laser and thulium have been introduced in for the treatment of NMIBC 9. Among them, thulium has gained popularity recently because it offers several advantages. First, the wavelength of thulium (about 2μm) is close to water absorption peak (1.94μm), which contributes to higher absorption of laser energy as
ACCEPTED MANUSCRIPT well as more efficient and precise tissue cutting6,10. At the same time, the continuous-wave laser makes it easy for steadily control and the operation-related complications of thulium are negligible. More importantly, it is possible for en bloc
RI PT
resection of bladder tumor with detrusor muscle for pathologic evaluation and staging6,10.
More recently, a cutting-edge thulium laser with 1.94μm wavelength (generated
SC
by Vela®XL system, StarMedTech, Starnberg, Germany), perfectly matched with
M AN U
water absorption peak, was introduced in our institution recently. The purpose of the present preliminary study was to evaluate the efficacy and safety of 1.94μm thulium laser (Vela®XL system, StarMedTech, Starnberg, Germany, 1.94μm) for en bloc resection of primary, papillary bladder tumor and shared our initial experience.
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Materials and methods
From January 2013 to August 2014, 38 patients were treated by 1.94μm thulium laser en bloc resection in our urologic department. Cystoscopy, computerized
EP
tomography, ultrasonography, intravenous pyelography were routinely performed to
AC C
select proper patients. The inclusion criteria were cystoscopic proved primary solitary bladder cancer, the diameter was between 0.5cm and 3cm. Exclusion criteria were bladder carcinoma in situ (CIS), coupled with mat-like neoplasms or upper urinary tract tumor, radiological examination suggested high probability of metastasis or tumor stage greater than T3. Informed consent was signed by each patient. This study was also approved by the ethic board in the Changhai hospital. Surgical Technique
ACCEPTED MANUSCRIPT Under general anesthesia, the patients were positioned in a lithotomic position. Routine cystoscopy was performed to confirm the location, number, and volume of the bladder tumor. Physiologic sodium solution was used for irrigation, a re-usable
RI PT
600μm laser fiber was advanced via the working channel of a 26F continuous flow resectoscope (Karl Storz GmbH, Tuttlingen, Germany) which was connected to a
video monitor system. The Vela laser was set at 50w for cutting. The procedures of
SC
en bloc resection were illustrated in the Figure 1. The cool cut mode (Cool Cut®
M AN U
system integrated with Vela®XL system) was activated when deal with the base of the tumor, so as to reduce carbonization for correct pathologic staging. Tumors at blind zone of resectoscope, for example at 12 o’clock direction of bladder neck, was removed by utilizing an 18 F flexible cystoscope (CYF-2, Olympus, Japan), a previous
TE D
method reported by Gao et al.6 in our center. Intact tumor was flashed out or extracted with a grasper. Randomly cold-forceps biopsy samples were taken from the muscle layer beneath the tumor base, normal looking tumor margin and bladder wall.
EP
Thereafter, adequate coagulation was performed at the tumor ground and
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surrounding mucosa. Catheter was inserted after verifying no hemorrhage. Immediate intravesical instillation with epirubicin (50 mg, Pfizer Pharmaceuticals Ltd ) was performed within 24 hours after surgery. High risk patients maintained weekly instillation for 8 weeks and then followed by monthly management for 1 year. Data collection Total operation time, tumor location and size, intraoperative complications, e.g. bladder perforation, obturator nerve reflex were recorded. Postoperative
ACCEPTED MANUSCRIPT information such as bleeding, catheterization time, hospital stay were collected as well. Pathologic examination was based upon 2009 TNM classification and the 2004 World Health Organization grading system. All patients were followed up at least one
RI PT
year, cystoscopy was conducted at 3-month intervals, urine cytology and radiological imaging examinations were performed at the discretion of urologists. Results
SC
The mean age of the 38 patients (31 males and 7 females) were 62 year-old (rang
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42 to 78 years). Bladder tumors were located on the lateral wall (15 cases), trigone (13 cases), posterior wall (6 cases), and bladder dome (4 cases). The mean diameter of tumor was 2.1cm (range 0.8 to 3.0cm). The average total operation time was 23 minutes (range 15 to 43 minutes). All the tumors were en bloc removed successfully,
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with 2 cases (5.3%, located at the bladder dome) requiring flexible cystoscope for better management. No complication occurred within or after operation. 4 patients (10.5%) with sessile tumors or big tumor ground needed bladder perfusion for 1 day.
EP
The catheter removed on the following day or the second day. The median
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postoperative hospital stay was 3 days (range 2 to 20 days). One patient with T2b tumor performed laparoscopic cystectomy 1 week after initial surgery. Pathologic evaluations showed all the en bloc specimens contained muscle layers,
15 patients with pTa, 22 patients with pT1, and 1 patient with pT2b. Grade classification found 20 patients in low grade or papillary urothelial neoplasm of low malignant potential and 18 patients in high grade. All the cold-cut randomly biopsied specimens were tumor free, except the T2b patients with residual tumor in the
ACCEPTED MANUSCRIPT detrusor muscle specimen. The mean follow-up duration was 21.8 months (range 14 to 34 months), the recurrence rate were displayed in Table 1. The one year recurrence rate was 5/17(29.4%) and 3/20(15%) for high grade and low grade tumor,
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respectively (T2b patient was excluded from recurrence analysis). Discussion
Since Stern11 invented the first resectoscope for bladder tumor resection in 1926,
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TURBT has now been considered as the gold standard treatment of NMIBC and an
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essential step for diagnosing muscle infiltrating bladder cancer in the guideline of European Association of Urology (EAU) and American Urological Association3,5. However, there are still several limitations with TURBT, which can be associated with significant perioperative or postoperative morbidity. Collado et al.12 reported a series
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of 2821 TURBTs with 145 complications (5.1%), the most common complication was bleeding (2.8%), with 3.4% patients need blood transfusion, and another common complication was perforations, which occurred in 1.3% of patients. Kihl et al.13 also
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found 10.6% of patients suffered obturator spasm during operation in a series of 160
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TURBTs. Rare complication such as bladder explosion, occurred when electrical spark ignited the mixed air and hydrogen, was reported recently as well14. Furthermore, the “incise and scatter’’ procedure of TURBT may contribute to tumor recurrence, and thermal damage caused carbonization as well as tissue fragmentation significantly hamper accurate pathohistological evaluation6,7,9. Based on the EAU guidelines, a second TURBT should be performed within 2-6 weeks if the first resection could not give accurate pathologic evaluation3.
ACCEPTED MANUSCRIPT Nowadays, various laser devices have been introduced in clinical practice as an alternative choice for TURBT, showing good results in terms of complications and pathologic staging. Until now, holmium and thulium laser for bladder tumor
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resection are the most frequent used technique for NMIBC treatment9. Totally, 800 patients were reported had underwent either Ho:YAG laser or thulium laser therapy (Ho:YAG = 652 patients and thulium = 148 patients) in 18 English publications,
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demonstrating the advantages of laser resection in safety and efficacy over TURBT9.
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Thulium laser was first introduced in clinical practice in our institution in 2005, since then it has become one of the most innovative lasers applied in urological surgeries6,15. Recently, Vela laser, a new kind of thulium laser, with 1.94μm wavelength was introduced in our center. From our preliminary experience, Vela
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laser possessed the advantages of thulium laser that have been reported before, e.g. better hemostasis, precise penetration depth of only 0.2 mm, a continuous wave mode make it possible to be kept steadily and can be used like an electric knife,
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obturator reflex was less likely to happen6,7,10. Several studies even reported that en
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bloc resection of bladder tumor by thulium laser could preserve the intact structure of the tumor for pathologic evaluation7,10. However, from our previous experience by using thulium laser for resection, the architectural detail of tumor could be distorted, making it difficult for the pathologist to diagnose accurately, especially for stage6. Nevertheless, we could make use of the cool cut function of the Vela laser device when resecting tumor base, this could help to preserve the architecture of the en bloc tumor, solving the predicament we have mentioned before.
ACCEPTED MANUSCRIPT So far, en bloc bladder tumor resection techniques have been applied in 11 publications (Ho:YAG = 5, thulium = 5 and 1 compared Ho:YAG with thulium)9. The recurrence rate of en bloc resection by thulium laser ranged from 10.9% to 28% at 12
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months follow-up, while for Ho:YAG laser was 25% to 65.1%9. In the present study, the 1 year recurrence rate was 21.6%, matched to the data reported before and the result estimated by the calculators designed by the European Organization for the
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Research and Treatment of Cancer, that is, ranging from 15% to 24% at the first year.
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It seems that en bloc resection by laser is not possible to reduce recurrence rate compared with traditional TURBT, however, no prospective randomized control trial comparing the two methods has published yet to prove this. Even though, en bloc section by Vela laser was able to provide an intact tissue for accurate pathologic
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evaluation, tackling the problem caused by TURBT such as fragmentation, artifacts, thermal damages and tangential sections7,10. As a result, fewer patients need a second TURBT for tumor staging. Even though, there was still limitations with
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thulium laser en bloc section, the primary one was that it was now not suitable for
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multiple mat-like bladder tumor, CIS or large volume tumor, because it might be time-consuming and laborious to do so and likely to neglect CIS tumor. Second, it required proficient surgical skills to en bloc resect the tumor in the blind zone of rigid continuous flow resectoscope by utilizing flexible cystoscope. In conclusion, our results indicated that Vela laser was an effective, feasible and safe thulium laser for en bloc bladder tumor resection. It was associated with negligible intraoperative or postoperative complication and could bring accurate
ACCEPTED MANUSCRIPT pathologic evaluation, so Vela laser resection could be regarded as an alternative approach for NMIBC treatment. Furthermore, large prospective, randomized control studies with an extended follow-up duration is needed to prove whether it can
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reduce recurrence rate of NMIBC compared with traditional TURBT. Clinical Practice Points
Transurethral resection of bladder tumor is associated with perioperative or
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the basic oncologic principles
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postoperative complications and “incise and scatter” procedure contradicts
In the present study, Vela laser, a new kind of thulium laser with 1.94μm wavelength, was used for treatment of 38 patients with non-muscle invasive bladder cancer.
Vela laser could be used for en bloc resection of bladder tumor, the one-year
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recurrence free rate was similar to TURBT, and this technique preserved the muscle layers for pathological evaluation. No complication occurred within or after operation, Vela laser was an effective,
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feasible and safe thulium laser for en bloc bladder tumor resection.
Acknowledgement: This study was supported by the foundation of Excellent Academic Leaders of Shanghai (XBR2013076)
ACCEPTED MANUSCRIPT References 1.
Siegel R, Ma J, Zou Z, et al. Cancer statistics, 2014. CA Cancer J Clin 2014; 64: 9-29.
2.
Sievert KD, Amend B, Nagele U, et al. Economic aspects of bladder cancer: what are the benefits and costs? World J Urol 2009; 27: 295-300.
3.
Babjuk M, Burger M, Zigeuner R, et al. EAU guidelines on non-muscle-invasive urothelial
4.
Traxer O, Pasqui F, Gattegno B, et al. Technique and complications of transurethral surgery for
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carcinoma of the bladder: update 2013. Eur Urol 2013; 64: 639-653. bladder tumours. BJU Int 2004; 94: 492-496. 5.
He D, Fan J, Wu K, et al. Novel Green-Light KTP Laser En Bloc Enucleation for
Nonmuscle-Invasive Bladder Cancer: Technique and Initial Clinical Experience. J Endourol 2014; 28: 975-979.
Gao X, Ren S, Xu C, et al. Thulium laser resection via a flexible cystoscope for recurrent
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6.
non-muscle-invasive bladder cancer: initial clinical experience. BJU Int 2008; 102: 1115-1118. 7.
Wolters M, Kramer MW, Becker JU, et al. Tm:YAG laser en bloc mucosectomy for accurate
8.
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staging of primary bladder cancer: early experience. World J Urol 2011; 29: 429-432. Staehler G, Schmiedt E and Hofstetter A. Destruction of bladder neoplasms by means of transurethral neodym-YAG-laser coagulation. Helv Chir Acta 1978; 45: 307-311. 9.
Kramer MW, Wolters M, Cash H, et al. Current evidence of transurethral Ho:YAG and Tm:YAG treatment of bladder cancer: update 2014. World J Urol 2014.
10.
Muto G, Collura D, Giacobbe A, et al. Thulium:yttrium-aluminum-garnet laser for en bloc resection of bladder cancer: clinical and histopathologic advantages. Urology 2014; 83:
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851-855. 11.
Stern M. Resection of obstructions at the vesical orifice. J Am med Ass 1926; 87: 1726-1730.
12.
Collado A, Chechile GE, Salvador J, et al. Early complications of endoscopic treatment for superficial bladder tumors. J Urol 2000; 164: 1529-1532.
13.
Kihl B, Nilson AE and Pettersson S. Thigh adductor contraction during transurethral resection
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of bladder tumours: evaluation of inactive electrode placement and obturator nerve topography. Scand J Urol Nephrol 1981; 15: 121-125. 14.
Khan A, Masood J, Ghei M, et al. Intravesical explosions during transurethral endoscopic
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procedures. Int Urol Nephrol 2007; 39: 179-183. 15.
Yang D, Xue B, Zang Y, et al. Efficacy and safety of potassium-titanyl- phosphate laser vaporization for clinically non-muscle invasive bladder cancer. Urol J 2014; 11: 1258-1263.
ACCEPTED MANUSCRIPT Figure 1. Procedures for Vela laser en bloc bladder tumor resection. A. Laser fiber was inserted to the bladder; B. A 2mm safe margin was made around the tumor base; C. Dissect bladder mucosa into the detrusor muscle layer with cool cut function; D.
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Separate tumor en bloc from tumor ground; E. An intact bladder tumor with muscle
coagulation.
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Table 1 Follow-up total recurrence rate
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layer was separated; F. Extended resection of the tumor base and adequate
ACCEPTED MANUSCRIPT Table 1 Follow-up total recurrence rate *
Primary site New site Total
3 mo 0 0 0
Time (months) 6 mo 12 mo 0 1/37 (2.7%)b 3/37 (8.1)a 7/37 (18.9%)c 3/37 (8.1) 8/37 (21.6%)
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No. of recurrences/Total (%)
The patient who underwent cystectomy was excluded for recurrence analysis.
a
Two were high grade tumor, one was low grade tumor.
b
The one was high grade tumor
c
Three were low grade tumor, Four were high grade tumor.
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EP
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*
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ACCEPTED MANUSCRIPT
S1558-7673(16)30150-1
DOI:
10.1016/j.clgc.2016.06.004
Reference:
CLGC 633
To appear in:
Clinical Genitourinary Cancer
Received Date: 20 November 2015 Accepted Date: 5 June 2016
Please cite this article as: Zhang Z, Zeng S, Zhao J, Lu X, Xu W, Ma C, Wang Y, Chen X, Jia G, Sun Y, Xu C, A pilot study of Vela laser for en bloc resection of papillary bladder cancer, Clinical Genitourinary Cancer (2016), doi: 10.1016/j.clgc.2016.06.004. 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.
ACCEPTED MANUSCRIPT Title: A pilot study of Vela laser for en bloc resection of papillary bladder cancer Authors: Zhensheng Zhang1#, Shuxiong Zeng1#, Junjie Zhao1, Xin Lu1,
RI PT
Weidong Xu1, Chong Ma1, Yang Wang2, Xin Chen1, Gaozhen Jia1，Yinghao Sun1*, Chuanliang Xu1*
Short Title： ：Vela laser for en bloc bladder tumor resection
SC
Key Words： ：Thulium laser, bladder cancer, en bloc resection, TURBT
Financial Disclosures: The authors declare that they have no relevant
M AN U
financial interests.
Funding Support: This study did not receive any funding support. #
Zhensheng Zhang, Shuxiong Zeng contributed equally to the paper and are
cofirst authors 1
TE D
From the Department of Urology, Changhai Hospital, Second Military Medical
University, Shanghai, P. R. China 2
EP
From the Department of Pathology, Changhai Hospital, Second Military
Medical University, Shanghai, P. R. China *
AC C
Correspondence: Yinghao Sun, Ph.D., M.D., Chuanliang Xu Ph.D., M.D.
Department of Urology, Changhai Hospital, Second Military Medical University, 168
Changhai
Rd,
Shanghai
200433,
P.
R.
[email protected]; [email protected]
China.
E-mail:
ACCEPTED MANUSCRIPT Microabstract Transurethral resection of bladder tumor is associated with perioperative or postoperative complications, and “incise and scatter” procedure contradicts the
RI PT
basic oncologic principles. The present study introduced Vela laser, a new kind of thulium laser with 1.94μm wavelength, for en bloc resection of bladder tumor. The
feasible and safe for patients with bladder tumor.
Objectives
M AN U
Abstract
SC
pilot experience found Vela laser could preserve the muscle layer and was effective,
To evaluate the safety and efficacy of Vela laser for en bloc resection of
papillary bladder tumor.
Materials and methods From January 2013 to August 2014, 38 patients were
TE D
treated by Vela laser en bloc resection with 26F continuous flow resectoscope or 18 F flexible cystoscope. Randomly cold-forceps biopsy samples were also performed. Total operation time, pathologic result, intraoperative or postoperative complications
The average total operation time was 23 minutes, All the tumors were en
AC C
Results
EP
were recorded. Each patient was followed at least one year.
bloc removed successfully, with 2 cases located at the bladder dome requiring flexible cystoscope for better management. No complication occurred within or after operation. All of resected tumor was intact with detrusor muscle layer and architecture for pathologic evaluation. One patient with T2b tumor performed laparoscopic cystectomy 1 week after initial surgery. At a median follow-up of 21.8 month, the recurrence rate at 12th month was 8/37 (21.6%).
ACCEPTED MANUSCRIPT Conclusion
Vela laser was an effective, feasible and safe thulium laser for en bloc
bladder tumor resection, it was associated with negligible complication and can bring accurate pathologic evaluation. Vela laser can serve as an alternative treatment for
AC C
EP
TE D
M AN U
SC
RI PT
non-muscle invasive bladder cancer or infiltrating tumor diagnosis.
ACCEPTED MANUSCRIPT Introduction Bladder cancer is one of the most common tumors in genitourinary system. It was estimated to occur in more than 74,690 new cases and lead to 15,580 deaths in 2014
RI PT
in the USA1. Moreover, bladder cancer has the largest financial burden per patient among all kinds of malignant tumors, this is due to the high frequency of recurrence and progression which thus need lifelong monitoring and repetitive treatment 2.
SC
Most bladder cancers (75%) are non-muscle invasive bladder cancer (NMIBC) and
M AN U
transurethral resection of bladder tumor (TURBT) is regarded as the standard diagnostic and therapeutic method3. However, this technique may be associated with significant complications, e.g. bleeding, bladder perforation, obturator nerve reflex and even bladder explosion4. Furthermore, the main disadvantage of TURBT is the
TE D
“incise and scatter” procedure contradicts the basic oncologic principles and herein may cause implantation of exfoliated cancer cells and difficulty for pathologic evaluation5-7.
EP
In order to tackle the problems, mentioned above, related to TURBT, several new
AC C
kinds of laser-based surgical procedures have emerged . Staehler et al.8 first utilize neodymium (Nd): yttriumaluminum- garnet (YAG) laser device in bladder cancer treatment in 1978. By far, holmium (Ho) YAG, potassium-titanyl-phosphate (KTP) green-light laser and thulium have been introduced in for the treatment of NMIBC 9. Among them, thulium has gained popularity recently because it offers several advantages. First, the wavelength of thulium (about 2μm) is close to water absorption peak (1.94μm), which contributes to higher absorption of laser energy as
ACCEPTED MANUSCRIPT well as more efficient and precise tissue cutting6,10. At the same time, the continuous-wave laser makes it easy for steadily control and the operation-related complications of thulium are negligible. More importantly, it is possible for en bloc
RI PT
resection of bladder tumor with detrusor muscle for pathologic evaluation and staging6,10.
More recently, a cutting-edge thulium laser with 1.94μm wavelength (generated
SC
by Vela®XL system, StarMedTech, Starnberg, Germany), perfectly matched with
M AN U
water absorption peak, was introduced in our institution recently. The purpose of the present preliminary study was to evaluate the efficacy and safety of 1.94μm thulium laser (Vela®XL system, StarMedTech, Starnberg, Germany, 1.94μm) for en bloc resection of primary, papillary bladder tumor and shared our initial experience.
TE D
Materials and methods
From January 2013 to August 2014, 38 patients were treated by 1.94μm thulium laser en bloc resection in our urologic department. Cystoscopy, computerized
EP
tomography, ultrasonography, intravenous pyelography were routinely performed to
AC C
select proper patients. The inclusion criteria were cystoscopic proved primary solitary bladder cancer, the diameter was between 0.5cm and 3cm. Exclusion criteria were bladder carcinoma in situ (CIS), coupled with mat-like neoplasms or upper urinary tract tumor, radiological examination suggested high probability of metastasis or tumor stage greater than T3. Informed consent was signed by each patient. This study was also approved by the ethic board in the Changhai hospital. Surgical Technique
ACCEPTED MANUSCRIPT Under general anesthesia, the patients were positioned in a lithotomic position. Routine cystoscopy was performed to confirm the location, number, and volume of the bladder tumor. Physiologic sodium solution was used for irrigation, a re-usable
RI PT
600μm laser fiber was advanced via the working channel of a 26F continuous flow resectoscope (Karl Storz GmbH, Tuttlingen, Germany) which was connected to a
video monitor system. The Vela laser was set at 50w for cutting. The procedures of
SC
en bloc resection were illustrated in the Figure 1. The cool cut mode (Cool Cut®
M AN U
system integrated with Vela®XL system) was activated when deal with the base of the tumor, so as to reduce carbonization for correct pathologic staging. Tumors at blind zone of resectoscope, for example at 12 o’clock direction of bladder neck, was removed by utilizing an 18 F flexible cystoscope (CYF-2, Olympus, Japan), a previous
TE D
method reported by Gao et al.6 in our center. Intact tumor was flashed out or extracted with a grasper. Randomly cold-forceps biopsy samples were taken from the muscle layer beneath the tumor base, normal looking tumor margin and bladder wall.
EP
Thereafter, adequate coagulation was performed at the tumor ground and
AC C
surrounding mucosa. Catheter was inserted after verifying no hemorrhage. Immediate intravesical instillation with epirubicin (50 mg, Pfizer Pharmaceuticals Ltd ) was performed within 24 hours after surgery. High risk patients maintained weekly instillation for 8 weeks and then followed by monthly management for 1 year. Data collection Total operation time, tumor location and size, intraoperative complications, e.g. bladder perforation, obturator nerve reflex were recorded. Postoperative
ACCEPTED MANUSCRIPT information such as bleeding, catheterization time, hospital stay were collected as well. Pathologic examination was based upon 2009 TNM classification and the 2004 World Health Organization grading system. All patients were followed up at least one
RI PT
year, cystoscopy was conducted at 3-month intervals, urine cytology and radiological imaging examinations were performed at the discretion of urologists. Results
SC
The mean age of the 38 patients (31 males and 7 females) were 62 year-old (rang
M AN U
42 to 78 years). Bladder tumors were located on the lateral wall (15 cases), trigone (13 cases), posterior wall (6 cases), and bladder dome (4 cases). The mean diameter of tumor was 2.1cm (range 0.8 to 3.0cm). The average total operation time was 23 minutes (range 15 to 43 minutes). All the tumors were en bloc removed successfully,
TE D
with 2 cases (5.3%, located at the bladder dome) requiring flexible cystoscope for better management. No complication occurred within or after operation. 4 patients (10.5%) with sessile tumors or big tumor ground needed bladder perfusion for 1 day.
EP
The catheter removed on the following day or the second day. The median
AC C
postoperative hospital stay was 3 days (range 2 to 20 days). One patient with T2b tumor performed laparoscopic cystectomy 1 week after initial surgery. Pathologic evaluations showed all the en bloc specimens contained muscle layers,
15 patients with pTa, 22 patients with pT1, and 1 patient with pT2b. Grade classification found 20 patients in low grade or papillary urothelial neoplasm of low malignant potential and 18 patients in high grade. All the cold-cut randomly biopsied specimens were tumor free, except the T2b patients with residual tumor in the
ACCEPTED MANUSCRIPT detrusor muscle specimen. The mean follow-up duration was 21.8 months (range 14 to 34 months), the recurrence rate were displayed in Table 1. The one year recurrence rate was 5/17(29.4%) and 3/20(15%) for high grade and low grade tumor,
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respectively (T2b patient was excluded from recurrence analysis). Discussion
Since Stern11 invented the first resectoscope for bladder tumor resection in 1926,
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TURBT has now been considered as the gold standard treatment of NMIBC and an
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essential step for diagnosing muscle infiltrating bladder cancer in the guideline of European Association of Urology (EAU) and American Urological Association3,5. However, there are still several limitations with TURBT, which can be associated with significant perioperative or postoperative morbidity. Collado et al.12 reported a series
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of 2821 TURBTs with 145 complications (5.1%), the most common complication was bleeding (2.8%), with 3.4% patients need blood transfusion, and another common complication was perforations, which occurred in 1.3% of patients. Kihl et al.13 also
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found 10.6% of patients suffered obturator spasm during operation in a series of 160
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TURBTs. Rare complication such as bladder explosion, occurred when electrical spark ignited the mixed air and hydrogen, was reported recently as well14. Furthermore, the “incise and scatter’’ procedure of TURBT may contribute to tumor recurrence, and thermal damage caused carbonization as well as tissue fragmentation significantly hamper accurate pathohistological evaluation6,7,9. Based on the EAU guidelines, a second TURBT should be performed within 2-6 weeks if the first resection could not give accurate pathologic evaluation3.
ACCEPTED MANUSCRIPT Nowadays, various laser devices have been introduced in clinical practice as an alternative choice for TURBT, showing good results in terms of complications and pathologic staging. Until now, holmium and thulium laser for bladder tumor
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resection are the most frequent used technique for NMIBC treatment9. Totally, 800 patients were reported had underwent either Ho:YAG laser or thulium laser therapy (Ho:YAG = 652 patients and thulium = 148 patients) in 18 English publications,
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demonstrating the advantages of laser resection in safety and efficacy over TURBT9.
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Thulium laser was first introduced in clinical practice in our institution in 2005, since then it has become one of the most innovative lasers applied in urological surgeries6,15. Recently, Vela laser, a new kind of thulium laser, with 1.94μm wavelength was introduced in our center. From our preliminary experience, Vela
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laser possessed the advantages of thulium laser that have been reported before, e.g. better hemostasis, precise penetration depth of only 0.2 mm, a continuous wave mode make it possible to be kept steadily and can be used like an electric knife,
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obturator reflex was less likely to happen6,7,10. Several studies even reported that en
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bloc resection of bladder tumor by thulium laser could preserve the intact structure of the tumor for pathologic evaluation7,10. However, from our previous experience by using thulium laser for resection, the architectural detail of tumor could be distorted, making it difficult for the pathologist to diagnose accurately, especially for stage6. Nevertheless, we could make use of the cool cut function of the Vela laser device when resecting tumor base, this could help to preserve the architecture of the en bloc tumor, solving the predicament we have mentioned before.
ACCEPTED MANUSCRIPT So far, en bloc bladder tumor resection techniques have been applied in 11 publications (Ho:YAG = 5, thulium = 5 and 1 compared Ho:YAG with thulium)9. The recurrence rate of en bloc resection by thulium laser ranged from 10.9% to 28% at 12
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months follow-up, while for Ho:YAG laser was 25% to 65.1%9. In the present study, the 1 year recurrence rate was 21.6%, matched to the data reported before and the result estimated by the calculators designed by the European Organization for the
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Research and Treatment of Cancer, that is, ranging from 15% to 24% at the first year.
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It seems that en bloc resection by laser is not possible to reduce recurrence rate compared with traditional TURBT, however, no prospective randomized control trial comparing the two methods has published yet to prove this. Even though, en bloc section by Vela laser was able to provide an intact tissue for accurate pathologic
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evaluation, tackling the problem caused by TURBT such as fragmentation, artifacts, thermal damages and tangential sections7,10. As a result, fewer patients need a second TURBT for tumor staging. Even though, there was still limitations with
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thulium laser en bloc section, the primary one was that it was now not suitable for
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multiple mat-like bladder tumor, CIS or large volume tumor, because it might be time-consuming and laborious to do so and likely to neglect CIS tumor. Second, it required proficient surgical skills to en bloc resect the tumor in the blind zone of rigid continuous flow resectoscope by utilizing flexible cystoscope. In conclusion, our results indicated that Vela laser was an effective, feasible and safe thulium laser for en bloc bladder tumor resection. It was associated with negligible intraoperative or postoperative complication and could bring accurate
ACCEPTED MANUSCRIPT pathologic evaluation, so Vela laser resection could be regarded as an alternative approach for NMIBC treatment. Furthermore, large prospective, randomized control studies with an extended follow-up duration is needed to prove whether it can
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reduce recurrence rate of NMIBC compared with traditional TURBT. Clinical Practice Points
Transurethral resection of bladder tumor is associated with perioperative or
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the basic oncologic principles
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postoperative complications and “incise and scatter” procedure contradicts
In the present study, Vela laser, a new kind of thulium laser with 1.94μm wavelength, was used for treatment of 38 patients with non-muscle invasive bladder cancer.
Vela laser could be used for en bloc resection of bladder tumor, the one-year
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recurrence free rate was similar to TURBT, and this technique preserved the muscle layers for pathological evaluation. No complication occurred within or after operation, Vela laser was an effective,
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feasible and safe thulium laser for en bloc bladder tumor resection.
Acknowledgement: This study was supported by the foundation of Excellent Academic Leaders of Shanghai (XBR2013076)
ACCEPTED MANUSCRIPT References 1.
Siegel R, Ma J, Zou Z, et al. Cancer statistics, 2014. CA Cancer J Clin 2014; 64: 9-29.
2.
Sievert KD, Amend B, Nagele U, et al. Economic aspects of bladder cancer: what are the benefits and costs? World J Urol 2009; 27: 295-300.
3.
Babjuk M, Burger M, Zigeuner R, et al. EAU guidelines on non-muscle-invasive urothelial
4.
Traxer O, Pasqui F, Gattegno B, et al. Technique and complications of transurethral surgery for
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carcinoma of the bladder: update 2013. Eur Urol 2013; 64: 639-653. bladder tumours. BJU Int 2004; 94: 492-496. 5.
He D, Fan J, Wu K, et al. Novel Green-Light KTP Laser En Bloc Enucleation for
Nonmuscle-Invasive Bladder Cancer: Technique and Initial Clinical Experience. J Endourol 2014; 28: 975-979.
Gao X, Ren S, Xu C, et al. Thulium laser resection via a flexible cystoscope for recurrent
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6.
non-muscle-invasive bladder cancer: initial clinical experience. BJU Int 2008; 102: 1115-1118. 7.
Wolters M, Kramer MW, Becker JU, et al. Tm:YAG laser en bloc mucosectomy for accurate
8.
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staging of primary bladder cancer: early experience. World J Urol 2011; 29: 429-432. Staehler G, Schmiedt E and Hofstetter A. Destruction of bladder neoplasms by means of transurethral neodym-YAG-laser coagulation. Helv Chir Acta 1978; 45: 307-311. 9.
Kramer MW, Wolters M, Cash H, et al. Current evidence of transurethral Ho:YAG and Tm:YAG treatment of bladder cancer: update 2014. World J Urol 2014.
10.
Muto G, Collura D, Giacobbe A, et al. Thulium:yttrium-aluminum-garnet laser for en bloc resection of bladder cancer: clinical and histopathologic advantages. Urology 2014; 83:
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851-855. 11.
Stern M. Resection of obstructions at the vesical orifice. J Am med Ass 1926; 87: 1726-1730.
12.
Collado A, Chechile GE, Salvador J, et al. Early complications of endoscopic treatment for superficial bladder tumors. J Urol 2000; 164: 1529-1532.
13.
Kihl B, Nilson AE and Pettersson S. Thigh adductor contraction during transurethral resection
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of bladder tumours: evaluation of inactive electrode placement and obturator nerve topography. Scand J Urol Nephrol 1981; 15: 121-125. 14.
Khan A, Masood J, Ghei M, et al. Intravesical explosions during transurethral endoscopic
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procedures. Int Urol Nephrol 2007; 39: 179-183. 15.
Yang D, Xue B, Zang Y, et al. Efficacy and safety of potassium-titanyl- phosphate laser vaporization for clinically non-muscle invasive bladder cancer. Urol J 2014; 11: 1258-1263.
ACCEPTED MANUSCRIPT Figure 1. Procedures for Vela laser en bloc bladder tumor resection. A. Laser fiber was inserted to the bladder; B. A 2mm safe margin was made around the tumor base; C. Dissect bladder mucosa into the detrusor muscle layer with cool cut function; D.
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Separate tumor en bloc from tumor ground; E. An intact bladder tumor with muscle
coagulation.
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Table 1 Follow-up total recurrence rate
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layer was separated; F. Extended resection of the tumor base and adequate
ACCEPTED MANUSCRIPT Table 1 Follow-up total recurrence rate *
Primary site New site Total
3 mo 0 0 0
Time (months) 6 mo 12 mo 0 1/37 (2.7%)b 3/37 (8.1)a 7/37 (18.9%)c 3/37 (8.1) 8/37 (21.6%)
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No. of recurrences/Total (%)
The patient who underwent cystectomy was excluded for recurrence analysis.
a
Two were high grade tumor, one was low grade tumor.
b
The one was high grade tumor
c
Three were low grade tumor, Four were high grade tumor.
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*
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