INTRODUCTION
Among cancers of the urinary system, tumors of the bladder rank as the second most prevalent. It is estimated that around 75% to 85% of freshly identified bladder cancers are limited to the mucosal or submucosal layers, which are categorized as non-muscle-invasive bladder cancer (NMIBC) [1]. The standard approach for managing these tumors is transurethral resection of the bladder tumor (TURBT), followed by supplementary intravesical chemotherapy or immunotherapy [2]. Nevertheless, TURBT can result in complications including bleeding, obturator nerve reflex, and perforation of the urinary bladder, the latter of which is particularly serious [3].
An expertly executed initial TURBT is the crucial first step in treating NMIBC. Key factors indicating a successful TURBT include the thoroughness of the tumor removal and the presence of detrusor muscle tissue in the biopsy sample [4,5].
Currently, standard piecemeal resection TURBT is the method of choice due to its safety, practicality, and the extensive long-term data supporting its oncological results. However, it does face some drawbacks, especially regarding tissue fragmentation, dispersal of tumor cells, the risk of an obturator reflex leading to perforation, and a 30% to 50% chance of not obtaining detrusor muscle in the biopsy, necessitating further TURBT for restaging [6-8]. Additional issues include the possibility of significant bleeding requiring a 3-way Foley catheter postsurgery, issues with clot retention, and the prolonged use of a large resectoscope sheath in the urethra [3].
Numerous efforts have been initiated to address these drawbacks. It started with single-piece resection utilizing a specialized electrode, and subsequently progressed to employing Nd:YAG and holmium (Ho) lasers for the vaporization of tumors [9-11]. Nonetheless, these methods were primarily effective for small, recurrent lesions. The inaugural application of holmium laser for en bloc resection of principal bladder tumors was documented by Das et al. [12] in 1998. Since then, various studies have demonstrated the safety and effectiveness of laser en bloc resection for urinary bladder tumors [13-16]. However, this technique has not seen widespread implementation, largely due to inadequate data regarding the practicality of holmium laser en bloc resection for larger tumors and multiple lesions, efficient methods for extracting the excised tissue, and the quality of resection in relation to obtaining detrusor muscle in biopsies. In this discussion, we outline our method for utilizing holmium laser en bloc resection of urinary bladder tumors and the extraction of tissue with a low-power holmium laser. We also examined the feasibility, effectiveness, and safety related to perioperative complications associated with holmium laser enucleation for NMIBC, particularly concerning multiple and larger lesions.
MATERIALS AND METHODS
Our research took place between October 2022 and April 2024 at a specialized medical facility. The participants in this research were individuals who visited the Urology outpatient department at Medical College Kolkata for bladder tumors. They underwent either electrosurgical transurethral resection or holmium laser en bloc resection using a low-power holmium laser, following a thorough assessment in line with the set inclusion and exclusion criteria during the study duration. The study protocol received approval from the institutional ethics committee (MC/KOL/IEC/NONSPON/1723/12/2022) on December 6, 2022.
1. Surgical Technique
1) Transurethral resection of the bladder tumor
After the onset of anesthesia, the patient is positioned in the dorsal lithotomy stance. The procedure is carried out using either spinal or general anesthesia. In our facility, every patient receives spinal anesthesia combined with a bilateral nerve stimulator-assisted obturator nerve block. A bimanual bladder examination is conducted under anesthesia prior to the resection. The TURBT is performed following an indepth pancryptoscopic assessment with a 30° lens to achieve the best evaluation of the urethra, prostate, and bladder, including the bladder neck. Suprapubic pressure may be necessary on the anterior wall and dome of the bladder for improved visualization.
It is crucial to avoid excessive filling of the bladder during tumor removal to reduce the risk of accidental perforation. A bimanual examination of the bladder is also conducted under anesthesia following resection for staging purposes. A palpable or movable mass may indicate cT3 disease, while a fixed mass could suggest cT4 disease. Completely eliminating the tumor is the most vital aspect of TURBT. If extensive red, velvety flat lesions are present, indicating carcinoma in situ, it is not advisable to excise the entire lesion; instead, a selective biopsy is adequate, with the intention of pursuing intravesical therapy.
Traditionally, larger tumors are removed gradually in pieces. This method involves multiple layers of resection until the detrusor muscle is reached. Careful use of cautery is practiced to prevent potential cautery artifacts on the specimen, as they may hinder accurate pathological assessment for tumor grading or staging.
2) Holmium laser en bloc resection of bladder tumor
Spinal anesthesia was administered to all individuals by the anesthesia team without utilizing any obturator nerve block. Subsequently, the patient was positioned in lithotomy. Every procedure was conducted by the same surgeon.
A thorough bimanual examination was carried out, followed by a standard white light cystoscopy utilizing a 20F cystoscope sheath to verify the dimensions and location of the tumor. A 26F resectoscope sheath was then inserted along with the visual obturator. Upon placing the resectoscope into the urinary bladder, the obturator was taken out, and the laser working element was inserted. A 550-μ holmium laser fiber was introduced through this working element. We operated with a 30-W holmium laser device. The laser equipment was produced by Quanta System SpA. The settings for laser energy were configured to 1.5 J, with a frequency of 15 Hz and a power output of 22.5 W (Fig. 1). Normal saline (0.9%) was used as the irrigant in all instances.
Initially, the laser was employed to delineate the boundaries of the tumor. Following that, the laser beam was utilized to deepen the marked edges (Fig. 2). En bloc resection commenced at the 6 o’clock position and progressively advanced toward the 12 o’clock position. In cases of minor hemorrhaging, hemostasis was achieved with the laser. It is crucial to maintain the incision at the detrusor level beneath the tumor during the entire procedure. After deepening the incision, the tumor is ultimately reduced to a stalk, which is subsequently severed to finalize the en bloc resection.
Certain challenging areas for en bloc resection included the anterior wall and dome of the urinary bladder. For these specific cases, the base of the tumor is excised from the lateral side. The initial mucosal marking should be positioned laterally relative to the tumor, followed by incisions starting from the sides, progressively advancing toward the center of the tumor.
Following the en bloc resection of the tumor, tissue removal was performed using an Ellik bladder evacuator. In 15 instances within our research, the tumor size was too significant to be extracted through the Ellik bladder evacuator. Therefore, it was fragmented into 2 or more pieces prior to completing the resection to facilitate removal. In several cases, tissues were extracted with the aid of Double J stent removal forceps after inserting a 20F cystoscope. All patients received routine postoperative irrigation with normal saline.
Various intraoperative and postoperative factors were considered for our analysis, including obturator reflex, hematuria, perforation, catheterization duration, need for clot evacuation, and length of hospital stay.
2. Statistical Analysis
Categorical variables are represented as the number and percentage of patients and are analyzed across different groups through either Pearson chi-square test for Independence of Attributes or Fisher exact test, depending on the situation. Continuous variables are represented by mean, median, and standard deviation and are compared among groups using an unpaired t-test.
For the analysis, IBM SPSS Statistics ver. 25.0 (IBM Co., USA) was utilized. An alpha level of 5% was set, meaning that any p-value falling below 0.05 was deemed significant.
RESULTS
The tumor and patient details are tabulated in (Table 1) whereas the perioperative and postoperative characteristics are tabulated in Table 2. A total of 66% of the individuals in the TURBT group were male, while 34% were female, in contrast to the holmium laser en bloc resection of bladder tumor (HoEBRBT) group, which had 70% male and 30% female patients. Both categories saw the highest number of patients falling within the 60 to 69 age range. In the TURBT cohort, 72% of patients had a solitary tumor, whereas in the HoEBRBT group, the figure was 74% for single tumors.
Regarding tumor sizes, 36% in the TURBT group exceeded 3 cm, while for the HoEBRBT group, that proportion was 24%. The predominant tumor locations in both categories were found on the lateral bladder walls. The average duration for en bloc resection was 34.56±10.516 minutes in the TURBT group, compared to 35.7±7.6 minutes in the HoEBRBT group, with no significant p-value detected. A total of 20% of patients within the TURBT group experienced obturator jerk during the procedure, whereas the HoEBRBT group reported no incidences of this issue. In comparison, the p-value is noteworthy at 0.001. In the TURBT group, 2 patients faced bladder perforation (BP), while the HoEBRBT group had no cases of perforation. Blood transfusions were necessary for 2 individuals in the TURBT group, whereas only 1 patient in the HoEBRBT group required a transfusion. Only 1 patient in the TURBT group needed clot evacuation due to intense bleeding, while this procedure was not required in the HoEBRBT group.
In the TURBT group, 78% of patients showed the presence of detrusor muscle in their biopsy samples, whereas the HoEBRBT group had 92% of patients with detrusor muscle observed in their biopsy results. When compared, the p-value of 0.046 indicates a significant difference, suggesting higher detrusor muscle presence in the HoEBRBT group.
The average catheterization duration was 2.78±1.02 days for patients in the TURBT group, while it was shorter at 1.78±0.68 days for those in the HoEBRBT group. The shorter duration in the HoEBRBT group is statistically significant based on the p-value of less than 0.001. The average hospitalization timeframe for the TURBT group was 3.24±0.59 days, whereas for the HoEBRBT group, it was 2.48±0.54 days. The stay was significantly reduced in the HoEBRBT group, as indicated by the p-value of less than 0.001.
DISCUSSION
In our investigation, the proportions of male and female participants were 66% and 34% in the TURBT cohort, while the HoEBRBT group comprised 70% males and 30% females [17].
Research indicates that bladder cancer predominantly affects males, with the incidence in men being as much as 4 times greater than that in women. Our findings imply a higher prevalence of urinary bladder cancer among males. The largest share of patients in the study were in their seventh decade of life. The average age at which bladder cancer is diagnosed is 73 years [18], surpassing the mean age of 65 for all types of cancer diagnoses. Both groups primarily presented with solitary tumors. Additionally, most tumors were found to be smaller than 3 cm in both sets of patients. The majority of tumors were situated in the lateral walls in both groups.
When evaluating results, there was no statistically meaningful difference in the average time taken for en bloc resection, which was 34.56±10.52 minutes for TURBT and 35.7±7.6 minutes for HoEBRBT. In the TURBT group, 10 individuals experienced obturator jerk, whereas the HoEBRBT group had none, highlighting a statistically significant difference with a p-value of 0.001.
In terms of BP, 2 patients in the TURBT group faced this issue while there were none affected in the HoEBRBT group. One study reported that 63 out of 114 patients experienced adductor spasms triggered by obturator stimulation during TURBT. Comparatively, there was no significant statistical difference in BP between the 2 groups. Literature indicates a varied incidence of BP, ranging from 1% to 10% [19-21]. We defined BP as any thorough resection of the bladder wall leading to observable extravasation of irrigating fluid or identification of perivesical fat during the procedure and ensured all perforations were noted, even for asymptomatic patients. Our rate of incidence appears low when contrasted with other studies that reported a 50% occurrence rate using routine postoperative cystograms to detect all perforations, no matter how minor, which may go unnoticed by surgeons in some cases [22].
With laser en bloc resection, obturator reflex does not manifest as no electrical energy is utilized. A study by Maheshwari et al. [23] noted that their patients did not exhibit any obturator reflex or BP.
In the TURBT group, blood transfusion was needed for just 2 patients, while only 1 patient in the HoEBRBT group required it. Severe hemorrhage necessitating clot evacuation occurred in only 1 patient in the TURBT group and was completely absent in the HoEBRBT group. Employing a holmium laser, Maheshwari et al. [23] discovered that only 4 out of 67 patients required significant bleeding management and postoperative clot evacuation. In cases of bleeding that necessitated clot removal, electrocautery was utilized for fulguration, and no patient required a blood transfusion. The detrusor muscle was identified in 78 percent of individuals within the TURBT cohort, in contrast to 92% in the HoEBRBT cohort. This variance is statistically significant, as indicated by a p-value of 0.046. Recent studies utilizing laser en bloc resection of bladder tumor (ERBT) have found detrusor-positive rates varying between 78% and 100% [9,24-27].
In the TURBT group, the mean catheterization period was 2.78 days, with a standard deviation of 1.02 days, while in the HoEBRBT group, it averaged 1.78 days with a standard deviation of 0.68 days. This difference is statistically significant, with a p-value below 0.001.
The duration of catheterization, averaging 1.78 days, aligns closely with findings from earlier studies on Ho ERBT, which is shorter than the times recorded for cTURBT [13,28,29].
During our initial procedures, we maintained catheters for 2 to 3 days, but as we gained experience, we decreased the catheterization time to between 24 and 36 hours. A recent review by Li et al. [27] indicates that the catheterization duration during laser bladder tumor resections diminishes by over a day on average.
The typical length of hospital stay was 3.24±0.59 days for the TURBT group, while the HoEBRBT group had an average of 2.48±0.54 days. This difference is statistically significant (p<0.001).
Recently, innovative methods like thulium laser en bloc resection of bladder tumors (TmLRBT) have emerged as an alternative to TURBT. A study led by Badawy et al. [30] compared TmLRBT with the traditional TURBT. Their findings indicated that TmLRBT resulted in shorter operation times and fewer perforation incidents. Additionally, TmLRBT revealed higher detection rates of detrusor muscle and minimized tissue damage in the pathological samples, alongside reduced recurrence of tumors. These conclusions imply that TmLRBT is a secure and effective replacement for TURBT in cases of tumors smaller than 4 cm.
TmLRBT also possesses advantages similar to HoEBRBT, including reduced duration of hospitalization and catheter use. This may be attributed to improved hemostasis, coupled with decreased instances of obturator reflex and BP. The TmLRBT method involves making a circular cut around the tumor while maintaining a 5-mm safety margin. Laser energy is then applied through this incision into the deeper muscle layers. Following that, a resectoscope is utilized to carefully separate the muscle fibers, employing laser primarily for hemostatic purposes and cutting any fibrous tissue that resists dissection. The laser’s ability to create clean cuts and cause minimal thermal injury helps achieve high-quality pathological specimens while safeguarding the detrusor muscle from thermal effects.
In a parallel investigation conducted in India by Choudhury et al. [31], it was determined that ThuLEBT serves as an effective and safe procedure for treating NMIBC and could effectively replace TURBT.
A study by Ortner et al. [32] aimed to discover the laser parameters and constraints utilized by specialists during laser vaporization (vapBT) and laser ERBTs, as well as to identify strategies for mitigating complications. They discovered that the thulium fiber laser (TFL) was the most frequently employed laser (57%), followed by holmium:yttriumaluminium-garnet (Ho:YAG) at 48%, continuous wave (cw) thulium:yttrium-aluminium-garnet (Tm:YAG) at 26%, and pulsed Tm:YAG at 13%.
Specialists demonstrated a preference for ERBT (91.3%) over vapBT (8.7%), although they acknowledged the existence of significant limitations such as tumor size, quantity, and anatomical positioning. While laser settings were generally similar, notable discrepancies were observed between the laser sources for lateral wall ERBT (p=0.028) and standard ERBT (p=0.033), with cwTm:YAG and pulsed Tm:YAG being utilized at higher power levels relative to TFL and Ho:YAG. Long pulse modes were favored for Ho:YAG lasers, while short pulse modes were preferred for TFL lasers.
In conclusion, TFL appears to have supplanted Ho:YAG and Tm:YAG. Most laser parameters do not show significant differences across various sources. Among experts, continuous flow irrigation is the most commonly implemented method for reducing complications.
The research mentioned above, in conjunction with this investigation, demonstrates that laser en bloc resection is a viable choice for treating urinary bladder cancers, as it has shown favorable outcomes both during and after the procedure. Various types of lasers have been utilized for en bloc resection, and a majority of them have shown effectiveness.
In our investigation, we employed a low-power holmium laser, which has shown significant efficacy for en bloc resection. Further studies extending over a longer duration are essential to validate the effectiveness of low-power holmium laser, as the primary objective of en bloc resection is to avert tumor recurrence, which necessitates longer follow-up periods for accurate assessment.
CONCLUSION
Though TURBT is deemed the optimal approach for handling urinary bladder cancers, utilizing holmium laser en bloc resection, even at lower power levels, presents an effective alternative for the treatment of such tumors due to its exceptional safety, practicality, and efficiency. This method is capable of achieving total resection of bladder tumors, regardless of their dimensions or positioning. Additional benefits include the elimination of the obturator reflex and consistent hemostasis during the procedure. The minimal necessity for bladder irrigation after surgery, alongside the high incidence of detrusor muscle presence in biopsy findings, underscores its safety and effectiveness. As indicated by our research, the average length of catheterization and hospital admission is considerably reduced in the holmium laser cohort. The learning curve associated with this technique is also manageable. holmium laser enucleation should be broadly implemented for the treatment of NMIBCs, as it can yield more extensive long-term outcomes.
The benefits of low-power holmium laser can be summarized in the following manner: outstanding coagulation abilities; accurate cutting; minimal tissue penetration depth (0.4 mm), which helps prevent urinary BP; cost-efficient; machine is easily transportable; better visualization of surgical field as compared to TURBT; low-power output (22.5 W) ensures that temperatures on the bladder wall do not exceed 60℃, reducing the risk of perforation.
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