High-power Green-light Laser Endoscopic Submucosal Dissection for Non-muscle-invasive Bladder Cancer
Condition: Bladder Cancer
MeSH terms: Urinary Bladder Neoplasms; Non-Muscle Invasive Bladder Neoplasms
Study type: Observational

Summary: 
      A retrospective study was designed in this study. The surgeon performed high-power
      green-light laser endoscopic submucosal dissection (HPL-ESD) for the treatment of primary
      non-muscle-invasive bladder cancer (NMIBC). This surgical treatment was novel and safety and
      efficacy of the treatment has not been established. We collected relative data in Shandong
      Provincial Hospital Affiliated to Shandong First Medical University from May 2018 to December
      2020. Preoperative, intraoperative and postoperative clinical data were collected and
      analysed. The safety and efficacy of the novel surgical treatment were verified by the
      short-term and long-term clinical outcomes. Fifty patients with NMIBC were planed to be
      enrolled in the study.
    

Detailed description: 
      Background: In recent years, endoscopic laser surgery has been introduced to the treatment of
      NMIBC. Various types of laser (holmium laser, thulium laser and green-light laser) have been
      examined in the treatment of NMIBC, and the cutting power has been raised gradually. In our
      previous study, a 120 W green-light laser was used to perform en bloc resection, which
      yielded encouraging results. Endoscopic submucosal dissection by the HybridKnife was reported
      to be safe and effective in the treatment of NMIBC. However, previous resection was performed
      by electrical instrument. To further enhance the safety and accuracy of the operation,
      surgeons improved the treatment by combining laser resection and endoscopic submucosal
      dissection (ESD). This novel surgical treatment can also integrate advantages of each method.
      A retrospective study was designed in this study. The aim of the study was to evaluate the
      safety and efficacy of this novel surgical treatment, high-power green-light laser endoscopic
      submucosal dissection (HPL-ESD), in the treatment of primary non-muscle-invasive bladder
      cancer (NMIBC).

      Introduction: Greenlight lasers are developed from Nd:YAG laser. Visual laser vaporization
      with Nd:YAG laser was introduced for the treatment of bladder cancer in the early 1990s.
      However, the low-absorption in most tissues with a penetration depth of 4-18mm leading to a
      deep coagulative necrosis of tissue, which increased the risk of delayed bladder perforation
      and bowel injury. Passing the Nd:YAG-produced beam (1046nm) through a KTP or LBO crystal,
      leads to a green visible light beam of 532nm, which has a completely different laser
      beam-tissue interaction. The wavelength is not absorbed by water but strongly absorbed by
      hemoglobin, which limits the optical penetration depth of green light laser to 0.8 mm, and
      the heat remaining in the tissue induces a coagulation zone of only 1-2mm thickness. Recent
      studies show that greenlight laser vaporization is a reliable and feasible treatment for the
      patients with primary NMIBC compared with standard TURBT.

      On the basis of our previous surgical procedure, we developed this new surgical method by
      introducing ESD technology. Thus LBO laser en bloc resection was combined with the ESD
      technique to treat NMIBC, which was inspired by waterjet-assisted ESD in the department of
      gastroenterology. ESD was developed from endoscopic mucosal resection (EMR) and widely
      applied for the treatment of early gastroesophageal cancer and colorectal neoplasms. The
      bladder wall shares a similar histological structure with the gastrointestinal tract,
      although the muscularis propria is thicker. Therefore, forming a submucosal fluid cushion in
      the bladder wall should be feasible and even safer. The effects of submucosal fluid cushion
      on bladder wall were showed intuitively. The interspace between the mucosal layer and the
      detrusor muscle layer was increased, and the tissue between the two layers was rendered
      looser. In the present study, the submucosal fluid cushion increases safety during the
      operation. More importantly, when the normal mucosa was incised, the detrusor muscle layer
      beneath was exposed, which facilitated distinction of which layer was reached and incision of
      the entire tumor with the superficial detrusor muscle beneath the basal part. To some extent,
      introduction of the ESD technique enabled safe, controllable and accurate incision.

      Equipment: The equipment included a 23F continuous flow resectoscope through which a 6F
      green-light lithium triborate (LBO) laser fiber (Realton, Beijing, China) could be delivered
      via the working channel. In addition, a disposable injector was used to form the submucosal
      fluid cushion for ESD. The stainless steel needle of the injector is 5 mm in length and 0.6
      mm in diameter (terminal part). The working length and diameter are 1650 mm and 2.5 mm
      respectively (middle part), enabling delivery through the working channel of the
      resectoscope. The beginning part of the injector was connected to a 20-ml syringe containing
      methylene blue solution as the injection fluid.

      HPL-ESD procedure: All surgeries were conducted in the lithotomy position under continuous
      epidural anesthesia. Sodium chloride physiological solution was used for irrigation. The 23F
      continuous flow resectoscope was delivered into the bladder through the urethra initially.
      Each visible tumor was examined to confirm the location, number, and size and the condition
      of the adjacent mucosa. Then, the 6F green-light LBO laser fiber was delivered through the
      working channel of the resectoscope. Each tumor was first marked with a circular coagulation
      blockage border, which was 1-2 cm from the edge of the tumor. Next, the laser fiber was
      temporarily withdrawn and the disposable injector was delivered through the same working
      channel of the resectoscope. Multipoint injection was performed in the normal mucosa along
      the blockage border. Because the tissue between the mucosal layer and the detrusor muscle
      layer in the bladder wall is relatively loose, a blue submucosal fluid cushion was formed
      between the two layers after injection. Subsequently, the green-light laser was delivered
      through the working channel again. The laser power was set at 160 W for cutting and 30-50 W
      for coagulation simultaneously. The mucosa was incised annularly, and the detrusor muscle
      layer beneath it was gradually exposed. The submucosal fluid cushion separated the mucosa
      layer and the detrusor muscle layer to some extent in advance. Therefore, the course and
      distribution of the detrusor muscle could be clearly observed. Dissection of tissue connected
      between the tumor and the bladder wall was also facilitated. The entire tumor was excised
      with superficial detrusor muscle beneath the basal part. After resection, the whole tumor bed
      and surrounding mucosa were carefully coagulated at a power of 30-50 W. The intact bladder
      tumor was removed with an alligator forceps or flushed out with an Ellik evacuator. When the
      tumor size was > 3 cm, the specimen was longitudinally cut into two or more parts.

      Clinical data will be collected, such as patient data, tumor characteristics, and
      perioperative data.
    

Observational model: Cohort
Time perspective: Retrospective
Sampling method: Probability Sample
Study population: 
        Patients with primary non-muscle invasive bladder cancer that received high-power green
        laser submucosal resection will be enrolled in this study. Gender is not limited. Most
        patients were elder male people with smoking history.