Holmium Versus Bipolar en Bloc Transurethral Resection of Urothelium Tumor of the Urinary Bladder: A Randomized Controlled Trial
Phase: PHASE2
Conditions: Urinary Bladder Neoplasm
Sponsor: Ain Shams University

 
 
 
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PROTOCOL OF A Randomized controlled trial (1/10/2020) 
 
Title of the Protocol:  
 
Holmium versus Bipolar en bloc transurethral resection of urothelium 
carcinoma of the urinary bladder 
 
 
Investigator: Dr. Ahmed Maher Gamil Ahmed Higazy 
Academic Position: Assistant Lecturer of Urology 
Department: Urology Department, Ain Shams University 
 
DIRECTOR: Dr. Ahmed Ibrahim Radwan 
Academic Position: Lecturer of Urology department  
Department: Urology Department, Ain Shams University 
 
 
 

 
 
 
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        What is already known on this subject? AND          
        What does this study add?  
En bloc resection of bladder tumors (ERBT) may improve staging quality and perioperative 
morbidity and influence tumour recurrence.(1) 
 
1. INTRODUCTION/ REVIEW  
Urothelial carcinoma of the bladder (UBC) is the second most common urological 
malignancy and represents a growing healthcare problem worldwide [1]. An aging
population in Western countries, as well as high tobacco consumption and poor 
occupational safety regulations in developing nations, has led to increasing incidence rates
[2]. Although the vast majority of newly diagnosed bladder cancers are for nonmuscle-
invasive disease (NMIBC) and may be treated with endourological procedures, correct 
initial staging is critical. The quality of transurethral resection of bladder tumors (TURBT) 
strongly determines patient prognosis and overall UBC treatment costs [3, 4].  
Various research groups have already reported promisingresults for laser en bloc resection 
of bladder tumors (ERBT) [2, 6, 10]. However, not every hospital has access to laser 
devices, which are expensive. Using an electrical current instead of lasers may be a 
promising alternative. Indeed, one of the first research groups to show that ERBT is 
feasible used a modified J-shaped electrode needle [11]. 
Goals of new strategies should include avoiding second TURBTs and lowering overall 
treatment regimens. TURBT is one of the most established urological procedures.
Modifications have mainly consisted of amendments designed to increase detection rates 
[5]. Modern laser technology has led to new alternatives to conventional TURBT
(cTURBT). The advocates of ERBT have three goals: to improve resection quality, lower 
perioperative complication rates, and decrease recurrence rates at resection sites. The 
present study is the first to compare the results of laser and electric en bloc resection of 
bladder cancer with respect to the aforementioned goals. 
To compare the clinical outcome in the form of safety and efficacy between Holmium and 
bipolar transurethral en bloc resection of urinary bladder tumors.  
2. AIM/ OBJECTIVES  
To compare the clinical outcome in the form of safety and efficacy between 
Holmium and bipolar transurethral en bloc resection of urinary bladder tumors.  
 
3. METHODOLOGY:  
Patients and Methods/ Subjects and Methods/ Material and Methods  
Type of Study: prospective randomized clinical trial 
Study Setting: Operation ward - Ain Shams University hospitals. 

 
 
 
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Study Period: 6/2020 till we finish the follow up period 
Study Population: Egyptian male patients attending Ain Shams University 
hospitals Urology clinic 
 
           Sample size: 75 
Group A: 35 (represent Holmium en bloc resection) 
           Group B: 35 (represent bipolar en bloc resection) 
After obtaining informed consent, patients will be randomized with a 1:1 ratio using sealed 
envelopes that will be prepared by the department’s ethical committee into 2 groups, group 
1 represent the Holmium en bloc resection procedure while group 2 represents bipolar en 
bloc resection. Patients will be blinded to the type of intervention as well as the data 
collector and the statistician.  
Intervention: all procedures will be done by an expert surgeon who performed over 50 
cases of en bloc urinary bladder tumor resection with each energy source. In group A, 
Holmium en bloc resection procedure will be done under either general or spinal 
anesthesia, using a Holmium laser device (Cyber Ho, Quanta device, Milano, Italy). We 
will use a 30-40-watt power, 1-2 joules and 20-30 MHz frequency for Group A and bipolar 
en bloc resection for Group B. A 550 nm flexible laser fiber will be used in group A and a 
bipolar resection loop for group B.  
 A circular incision will be made around the tumor; a distance will be maintained of 
approximately 5–10 mm from the tumor itself. Subsequently, the tumor will be bluntly 
dissected from the bottom while respecting the incision line. Care is to be taken to include 
detrusor muscle. HoLRBT will usually be set to 1.0–2.0 J and 15–30 Hz, generating total 
energy levels of 20–40 W. 
All patients will receive a transurethral catheter for postoperative bladder irrigation. Bladder 
irrigation will be started immediately after finishing surgery. Patients will receive early 
instillation therapy (EI) received 40 mg of mitomycin C (MMC) within the first 12 h after 
surgery. Tumor specimen will be preserved in formalin solution and sent for 
histopathological examination. 
1 month after the procedure, diagnostic cystoscopy will be performed for all patient to 
evaluate tumor complete resection and search for any residual tumors. 
 
            Inclusion criteria: Adult patients of both sexes presented with urinary bladder 
tumor aiming for complete resection as diagnosed by Ultrasound with or without CT prior 

 
 
 
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histopathological assessment.   
Exclusion criteria:  Patients with signs of extravesical tumor extension where complete 
resection will not beneficial or unable to proceed to complete resection due to huge tumor 
burden either huge single tumor more than 5 cm or multiple tumors that are not candidate 
for complete resection. 
 
Ethical Considerations: Approval will be obtained from the ethical committee at 
Ain shams University before starting the research. 
             Study Procedures: The patients will undergo the following: 
Preoperative: 
1) History:  
 
Including medical history, surgical history, drug history, previous oncological history if 
present. 
2) Clinical Examination: 
Including abdominal, pelvic and digital rectal examination (DRE). 
3) Laboratory investigations:  
As Haemoglobin level, serum creatinine, urea, sodium, potassium and prostate specific 
antigen (PSA). 
4) Radiological investigations:  
As pelvi-abdominal ultrasound, contrast enhanced CT scan on Abdomen and pelvis. 
Intraoperative: Vital data monitoring, operative time and the need for blood transfusion, 
obturator reflex, conversion to trans-urethral resection of the bladder tumor. Ay 
intraoperative complication will be recorded like bladder perforation. 
Postoperative Follow-up Protocol: 
Patients will be evaluated immediately postoperative with vital signs (Blood pressure, 
Heart rate), abdominal examination, degree of haematuria, haemoglobin level drop. 
Patients will be re-evaluated at 6 weeks and then regular follow up every 3 months for 1 
year to evaluate tumour recurrence by ultrasound and diagnostic cystoscopy. 
 
Data collection and outcome measures: 
Primary outcomes:  
 main primary outcomes have been selected for our study 
1. Conversion to the TURBT 

 
 
 
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Secondary Outcomes: 
1. Operative time 
2. Tumor size and stage 
3. Presence of detrusor muscle in resected sample  
4. Resected specimen’s edge  
5. Intraoperative complication like need for blood transfusion, bladder perforation 
6. Incidence of obturator reflex  
7. Post-operative drop in hemoglobin level, or hematuria  
8. Post-operative catheterization time in hours 
9. Postoperative irrigation time in hours 
10. Recurrence rate of tumors according to time interval of postoperative follow up by 
diagnostic cystoscopy 1 month after enucleation. 
11. Recurrence rate of tumors according to tumor location (same site recurrence Vs 
new site or both)  
Statistical Analysis: The data will be collected, processed and statistically analyzed. 
Description of the quantitative variable will be done as mean and standard deviation and 
student t-test will be used to compare the two groups in parametric data while the 
qualitative data will be shown as frequency and compared using Chi square test. The 
results will be considered significant with P-value less 0.05 and high significant if less than 
0.01, results with P-value ≥ 0.05 will be considered non-significant. Analysis of the data will 
be done using IBM SPSS software (Statistical program for social science version 21). 
 
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