Temperature Profiles During Laser Activation in Ureteroscopic Lithotripsy - a Prospective Clinical Study
Phase: NA
Conditions: Ureteral Stone
Sponsor: Haukeland University Hospital

Protocol: 
Temperature profiles during laser activation in ureteroscopic 
lithotripsy - a prospective clinical study 
 
 
Authors: 
Æsøy MS, MD 1,2 
Juliebø-Jones CP, MD 1,2 
Beisland C, MD PhD, Professor 1,2 
Ulvik Ø, MD PhD, Assoc. Professor 1,2 
 
Affiliations: 
1 Helse Bergen HF, Department of Urology, Haukeland University Hospital, Bergen, Norway 
2 Department of Clinical Medicine (K1), University of Bergen, Bergen, Norway 
 
The authors’ contributions to the study: 
Ø Ulvik is the project manager and is responsible for the overall progress of the study. He 
will write the study protocol, making the data registration forms, patient information and 
consent forms, apply for approval by The National Committees for Research Ethics in 
Norway and The Data Protection Authorities at Haukeland University Hospital (HUH). In 
addition, Ulvik will apply for registration in the research database for clinical trials, 
ClinicalTrials.gov. Ulvik will also be doing the ureteroscopies and follow-up in the study 
patients, sampling data and take part in the statistical analyses. In addition, he will 
contribute to the draft and will supervise the writing process of the manuscript. 
M Æsøy is, together with Ø Ulvik, the main investigator and will take part in all processes of 
the study (development of registration forms, performing ureteroscopies and follow-up of 
the patients, data sampling, statistical analyses). He will also be the first author of the main 
article, and is responsible for making the draft, revisions and writing the final manuscript. 

P Juliebø-Jones will contribute to the data collection, ureteroscopies and follow-up, drafting 
of the manuscript, revisions in addition to critical review of the final version. 
C Beisland will contribute to the design and content of the manuscript in addition to critical 
review of the final version. In addition, he will contribute to the data analyses. 
 
Background: 
The past 30 years, laser lithotripsy during ureteroscopy (URS) has been performed using 
Holmium: yttrium-aluminum-garnet laser (Ho:YAG). The Ho:YAG has been considered the 
gold-standard laser for URS because of its versatility, with the ability to break all kinds of 
stones in the urinary tract as well as tumor- and soft tissue ablation. Development of higher 
power laser technology has allowed the limits of what can be achieved with URS to be set 
even higher 1,2. In comparison to stone fragmentation, techniques such as dusting and 
popcorning often implement higher power settings (>20 W), and the efficacy associated with 
different strategies has been the focus of many studies 3-5. In recent times, the 
intraoperative safety of URS has gained increasing attention, particularly with regard to high 
intra-pelvic pressure (IPP) and raised temperature levels 6-9. The results of such studies 
include new recommendations for procedural techniques aimed at reducing the risk of 
complications. One such example is the avoidance of pressurized irrigation pumps 8. 
Recently, a new Thulium fiber laser (TFL) has been introduced. With the advent of the TFL, 
discussion surrounding high temperatures during lithotripsy and resultant thermal damage 
have been fueled further 10. Defining safe margins for laser settings is especially important 
for the TFL as no consensus exists for what is acceptable during URS. In a recent publication, 
some experts’ preferred settings for the TFL during URS were presented, and a variety of 
different settings was suggested included high power settings as high as 45 Watts 11. 
Earlier this year we investigated temperature profiles during URS laser activation with 
different lasers (TFL and Ho:YAG), laser settings and fiber sizes in a pre-clinical study 12. We 
found that the rise in temperature in the renal pelvis was negligible when low settings below 
8 Watts were used, even when the laser was activated continuously for 180 seconds. 
However, applying laser settings of 20 Watts resulted in a significant rise in temperature and 
the threshold for heat induced cell injury (43oC) was reach and trespassed after 
approximately 40-45 seconds of continuous laser activation depending on the size of the 
fiber. Using smaller fiber extended the time before 43oC was reached. These findings need to 

be confirmed in clinical studies. However, until then, we expect laser settings ≤ 20 Watts for 
lithotripsy in the renal pelvis to be safe with regards to temperature.  
To date, there are no clinical studies investigating intrarenal temperatures during URS laser 
treatment. Studying temperature profiles during URS laser activation in patients is therefore 
of critical importance and highly clinically relevant to define the safety of different laser 
settings and power.  
 
Aims of the study: 
The primary aim of this study is to investigate the temperature profiles in the renal pelvis 
during TFL laser activation using different settings. To this end, comparison of peak 
temperatures during laser activation for different settings is the main aim. Secondary aim is 
trying to define the duration of safe laser activation until the threshold for heat induced cell 
injury (43oC) is reach.  
 
Hypothesis: 
1. Laser activation using low settings is safe regarding intrarenal temperature.  
2. The peak temperature in the renal pelvis is higher when high power settings is used 
compared to when lower settings is used. H0: “There is no difference in peak 
temperatures in the renal pelvis regardless of the laser settings used.” 
3. The time before 43oC of intrarenal temperature is reach is longer for low laser 
settings (if 43oC is reach at all) compared to high settings. The corresponding H0 is 
that “there is no difference in time until 43oC is reached following laser lithotripsy 
with high and low laser settings.” 
 
Study design: 
The study is planned as a prospective clinical trial.  
 
Patients and data sampling: 
Patients ≥ 18 years with a ureteral stone (with or without a concomitant renal stone) and an 
indwelling nephrostomy tube scheduled for URS lithotripsy at the day surgery unit at HUH, 
are invited to be enrolled in the study. Due to the result of the pre-clinical study, a power 
analysis reveals that a total of 10 patients are considered sufficient for inclusion in the study. 

The following data need to be registered: 
• Preoperative status: 
 
Age, sex, ASA-status, comorbidity, indication for  
surgery, stone status, infection. 
• Peroperative characteristics: 
Primary surgeon, antibiotic prophylaxis,  
operative time, need for safety guide wire, type 
of endoscope (semi-rigid/flexible), balloon 
dilatation, impacted stone, successful access to 
the stone, laser settings, laser time and energy 
used, temperature measurements, retrieval of 
fragments or left for spontaneous passage, 
surgeon’s assessment of post endoscopic stone 
free status, complications, placement of JJ-stent. 
• Postoperative status: 
 
Length of hospital stay, immediate complications  
that need urgent treatment, complications after 
discharge requiring readmission, 3-months 
follow-up with CT scan (SFR, stricture rate).  
 
The data will be plotted in electronical registration forms. Completed registration-forms are 
exported to a SPSS database for statistical analyses. 
The registration-forms and the database will be stored at Helse-Bergen’s research server in a 
designated file assigned from the Data Protection Officer. An ID-Key file combining personal 
ID to the registration form will be stored at a designated server for this purpose at Helse-
Bergen’s research servers. Only the project manager (Øyvind Ulvik) will have access to this 
ID-Key file.  
The registration forms and the ID-Key file will be kept on the server for five years after the 
study has been completed in accordance with the law. After five years the data will be made 
anonymous in terms of deleting the ID-Key file. 
 
Power analysis: 
In the pre-clinical study, we found that the peak temperatures when activating the TFL laser 
continuously for 180 seconds using a 150μm fiber were 26.7oC, 32.8oC and 45.2oC for the 
laser settings of 0.4J/6Hz (2.4W), 0.8J/10Hz (8W) and 0.2J/100Hz (20W), respectively 12. The 

corresponding baseline temperature before activating the laser were 24.1oC, 24.5oC and 
25.3oC.   
We expect both the baseline and the peak temperatures to be approximately similar also 
during URS in real patients as the temperature of the irrigational fluid is the same as in the 
pre-clinical study (23 oC) 12.  
Peak temperatures for different laser settings will be compared using paired-samples t-test. 
Using the peak temperatures for the different laser settings found in the pre-clinical study, 
the sample size can be calculated for the clinical study assuming the peak temperature will 
be similar. As the peak temperatures for different laser settings will be compared within the 
same individual, paired samples t-test is used. The total number of patients required for 
comparison is therefore lower than if peak temperatures were measured for only one laser 
setting in each patient. In that case independent samples t-test would have been the correct 
test for comparison. 
The effect size is calculated to be 4.4 comparing peak temperatures at 2.4W and 8W, and 2.9 
comparing peak temperatures at 8W and 20W. The assumed peak temperatures for 2.4W, 
8W and 20W are 26.7oC, 32.8oC and 45.2oC, respectively. The corresponding standard 
deviations are assumed to be 0.8, 1.6 and 4.9, respectively. The α error probability is set to 
0.05 and the power (1-β error probability) is set to 0.8.  
Using G*Power, version 3.1.9.4 and IBM SPSS Statistics 27 for power analysis, the total 
sample size is calculated to be 3 when comparing 2.4W and 8W and 4 when comparing 8W 
and 20W. The highest number of these two calculations is considered appropriate to use. To 
compensate for possible non-evaluable patients, a total of 10 patients are planned for 
inclusion in the study.  
 
Statistical analyses: 
Statistical analyses will be performed using IBM SPSS Statistics 27 or higher (IBM, Armonk, 
NY). A p-value < 0.05 will determine statistical significance. 
Peak temperatures between different laser settings will be compared using paired-samples 
t-tests. Wilcoxon test for related samples will be used comparing the continuous 
temperature profiles for different laser settings. Exact χ2-test test and Fisher’s Exact test are 
used comparing categorical variables. 
 

Ethical considerations, ethical approval, and patient consent 
TFL is emerging as the laser of choice for ureteroscopic lithotripsy, and the laser has been 
demonstrated to be superior to the current gold-standard Ho:YAG laser regarding clinical 
outcomes 13. Despite being in daily use around the world, no consensus exists of what is 
considered the preferred laser settings and different experts recommend a variety of 
suggestions 11. Some of the laser settings preferred by experts exceeds 20W, which are 
settings found to be associated very high temperatures (> 43oC) 12. Defining safe laser 
settings with regard to temperatures therefore seems to be highly clinically relevant. The 
intra renal temperature is measured continuously during laser activation in the planned 
study, and laser activation is stopped immediately if the temperature reach 43oC for any 
laser setting. Participating in this study should therefore not expose the patients to extra risk 
of harm. The operative time will be extended by approximately 10 – 15 minutes for the 
patients in whom the ureteral stones cannot be pushed back into the renal pelvis for 
disintegration as the stone must be disintegrated in the ureter before temperature 
measurements can be performed in the renal pelvis in such patients. However, as the URS 
procedures are performed in general anaesthesia, the extra time caused by the temperature 
registration is not considered to cause any disadvantage for these patients. 
Applications for approval by The National Committees for Research Ethics in Norway and 
The Data Protection Authorities at HUH will be sent prior to study start. In addition, the 
study will be registered in the clinical research database for randomized trials, 
ClinicalTrials.gov. 
All patients eligible for inclusion in the study will receive oral and written information. 
Participation in the study is voluntarily, and the patient can choose to withdraw at any point 
during the study process. Inclusion in the study will only be done after the consent form is 
signed. The patient information and consent form used for this purpose is obtained from The 
National Committees for Research Ethics in Norway’s website 
(https://helseforskning.etikkom.no/frister/malforinformasjonsskriv?p_dim=34672). 
 
The URS procedure and follow-up 
Only patients with ureteral stones or combined ureteral and renal stones and who has an 
indwelling nephrostomy catheter are eligible for inclusion in the study.  

The URS procedure is performed in general anaesthesia and all patients will have 
prophylactic antibiotics prior to surgery start, either according to urine culture or current 
local regime. 
The procedure starts with a cystoscopy followed by semirigid URS when considered 
appropriate. Balloon dilatation is performed on demand. When reaching the stone, this is 
flushed back into the renal pelvis for disintegration there if possible. In cases where the 
stone cannot be flushed back into the renal pelvis, the stone is disintegrated in situ before 
the endoscope is advanced up to the renal pelvis for temperature measurements. Before 
laser disintegration, the semirigid ureteroscope is changed for a flexible ureteroscope 
(Olympus V3) that is advanced to the renal pelvis directly or over a guide wire that must be 
removed as soon as the endoscope is in place. An access sheath cannot be used during this 
study. Room-tempered (23oC), gravitational irrigation fluid at 60 cm height is used 
throughout the procedure. Manual pumping should be avoided and should in any case not 
be performed during the temperature measurements. Under endoscopic vision, a sterilized 
thermocouple sensor (K-type, same as in the pre-clinical study) is introduced through the 
nephrostomy tube so that the tip can identified through the side-holes of the nephrostomy 
tube. The sensors have undergone sterilization. Formal testing by the microbiological 
department at Haukeland University Hospital has verified this process successfully sterilizes 
the sensors.  The stone is moved to the central renal pelvis for laser disintegration, and a 
150μm laser fiber is introduced into the renal pelvis through the working channel of the 
flexible ureteroscope. At this point the nephrostomy tube is clamped to achieve filling of the 
renal pelvis and to mimic a normal procedure.  
Laser disintegration of the stone is started using the lowest laser setting of 5W continuously 
for 120 seconds followed by 60 seconds of idling laser. Temperature measurements are 
maintained continuously during these 180 seconds, with two measurements per second. 
When the temperature in the renal pelvis has reached base temperature after one series of 
measurements, the procedure is repeated for the next laser setting. In total, URS lithotripsy 
are performed for three different settings. If 43oC is reach during laser activation for any of 
the laser settings, the laser will be stopped immediately and further laser activation with 
that specific settings will be aborted. Laser activation with subsequent settings will be ready 
when base temperature is reached. 

If stone treatment is not completed at the end of the three series of laser activation and 
temperature measurements, further stone disintegration will be performed before finishing 
the URS procedure. A JJ-stent is placed at the end if deemed necessary by the surgeon. The 
nephrostomy tube is removed when considered appropriate. If a JJ-stent is placed after the 
procedure, this is removed according to standard routine after 1-2 weeks in the outpatient 
clinic. Follow-up with CT is performed at 3 months post endoscopically for all patients to 
assess stone free status and exclude a ureteral stricture in addition to a clinical consultation. 
 
Laser settings 
After reaching the renal pelvis with the flexible ureteroscope, the 150μm laser fiber is 
inserted through the working channel of the scope. The laser is then activated for 120 
seconds starting with the lowest settings. Temperature registration is then continued for 
another 60 seconds. When the temperature in the renal pelvis has returned to basic, the 
registration is repeated for the next laser settings. A total of 4 series is performed with 
different laser settings (2.4W, 8W, 20W and 30W) with 150μm laser fiber. Laser activation is 
immediately paused if the registered temperature reach 43oC.  The following laser settings 
will be used in the study: 
 
 
5 watts of power: 
0.5 J / 10 Hz, short pulse 
 
10 watts of power: 
0.5 J / 20 Hz, short pulse 
20 watts of power: 
0.5 J / 40 Hz, short pulse 
             30 watts of power:     1 J / 30 Hz, short pulse 
 
Study progress  
The date for completing the data registration form, patient information and consent form, 
and application for approval by The National Committees for Research Ethics in Norway is 
set to November 1st 2022.  
After achieving ethical approval, application for approval from The Data Protection 
Authorities at HUH will be sent. Prior to enrollment, the study also needs to be registered in 
the clinical research database for randomized trials, ClinicalTrials.gov. 
Inclusion of patients and ureteroscopies are expected to start in January 2023, and the 
inclusion is expected to close during June 2023.  

Data analyses and writing a draft is set to autumn/winter 2023. Final manuscript ready for 
submission is planned during January 2024. 
 
Funding 
No external funding is planned. Hopefully, the project can be completed during regular 
working hours at Haukeland University Hospital and the University of Bergen. 
 
Conflicts of interest 
Øyvind Ulvik is a consultant for Olympus, who is not involved in the design, collection, 
analyses, interpretation or reporting of the data. The other authors have nothing to disclose. 
 
Publication of data 
The results of the study are planned published as a manuscript in an international urological 
journal (Journal of Endourology, Urology or equivalent journal). Parts of the results may also 
be presented at international congresses 
 
 
Bergen 27.10.2022 
 
Øyvind Ulvik 
 
 
 
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