Stress urinary incontinence (SUI) is the involuntary leakage of urine during physical activity caused by bladder pressure exceeding urethral closure pressure. Slings are commonly used as a surgical treatment for SUI. However, the sling procedure is invasive and inserted into the body, resulting in mesh infection and chronic pain. The current study aims to evaluate the feasibility of laser treatment for SUI by using 980nm laser light with a balloon-integrated diffusing applicator as a minimally invasive and non-permanent procedure. A female porcine urethra was dilated using a balloon, and then the tissue was irradiated with the 980nm laser at 20W for 15s. The laser irradiated urethra were harvested 0, 14 and 28 days after the laser irradiation, respectively. Both Masson’s trichrome and Sirius red staining were applied to confirm structural changes and collagen distribution. There was no change in mucosal thickness between the laser irradiation group and the control group. In the laser irradiation group, the thickness of the muscle layer increased by approximately 35%, compared to the control group. Furthermore, the laser irradiation group showed a 30% increase in collagen distribution in the external urethral sphincter compared to the SUI model. The current study demonstrated the feasibility of the therapeutic effect of the 980nm laser in the porcine urethra. To confirm the safety and efficacy of the proposed photothermal treatment, we will conduct in vivo studies to assess the extent of nerve damage and molecular changes using PCR assays in chronic and disease-induced animal models.
Several therapeutic effects of photobiomodultion (PBM) on variable mucosal lesions of the upper aerodigestive tract has been reported. However, the biomodulatory effect of PBM are rarely reported on tracheostomy and tracheal fenestration, which has been increased with the spread of coronavirus disease (COVID-19). In this study, we developed a translaryngeal PBM therapy by using a basket-integrated diffusing applicator (BIDA) to ameliorate the wound healing of fenestrated tracheostoma after surgery. Tracheostomy was performed by using an electrocautery unit (Bovie) to develop an in vivo porcine model of fenestrated tracheostoma with impaired wounds. A 635 nm laser light (200 mW/cm2 for 3 min, 36 J/cm2) was applied to the wounds by using BIDA once daily for five days. BIDA was inserted in tracheostomy tube and emitted homogeneous circumferential light into the fenestrated wound without thermal damage. Control highly induced fibrotic expressions of alpha-smooth muscle actin and type-1 collagen with acute inflammation. In contrast, PBM reduced the expressions up to less than 82% of control. Histological scores presented that PBM significantly decreased acute inflammation and overgranulation to two-thirds of control with a small portion of abscess. In addition, a substantial difference in the lumen area was observed between the control and PBM due to the thickened wall. The current study demonstrated that the proposed PBM therapy could ameliorate the impaired wound healing of fenestrated tracheostoma as a result of modulated inflammation and fibrotic responses. Therefore, the translaryngeal PBM with BIDA can be an effective adjuvant therapy for managing the fenestrated wound after tracheostomy.
Stress urinary incontinence (SUI) is the unintentional loss of urine. Currently, catheter and artificial urinary sphincters are applied for SUI treatment. However, these treatments are invasive and require continuous usage. While Er:YAG and CO2 lasers are used as a minimal or non-invasive method, their treatment effects are limited to the superficial vaginal tissue and can often cause severe burns, leading to tissue destruction. The purpose of this study to investigate the feasibility of non-ablative 980-nm laser treatment for SUI. Numerical simulations were performed to confirm thermal effects in urethral tissue by employing the Pennes bioheat transfer and partial differential equations. Rabbit urethral tissue was used for experimental validations. A non-compliant balloon was used to expand the urethral tissue, and the 980 nm laser light was irradiated on the tissue at 20 W for 15 s. After the laser irradiation, the treated samples were stained with hematoxylin and eosin (HE) to evaluate any physical changes in the overall urinary structure. Masson trichrome (MT) staining was performed to analyze the extent of thermal injury in the collagen of the urethral tissue. A uniform and symmetrical temperature distribution was observed around the balloon surface in the simulation. The numerical simulations and experiments indicated that mucosal and muscle layers in the urethral tissue reached the temperatures of 24 °C and 31 °C, respectively. Histology analysis presented the overall urinary structure with a total outer diameter of 10 mm from the mucosal layer to the muscle layer. The MT staining revealed that both control and treated groups had similar amounts of collagen components without thermal damage. The current study demonstrated that the non-ablative 980 nm laser could warrant an effective method of treating SUI with no or minimal thermal damage.
Urethral stenosis is a narrowing of the urethra caused by inflammation, or surgical trauma. Although endoscopic managements have been applied for short stricture, high recurrence rates and complications have still remained. Recently, balloon-assisted cylindrical laser ablation using a diffusing applicator (DA) has been investigated to treat tubular tissue [1,2]. Even though previous studies confirmed the safety and efficacy [1,2], performance validation is still unmet for clinical situations. This study aims to establish treatment conditions by quantifying treatment length and depth for the clinical translation. Ex vivo experiment on porcine liver tissue was conducted to compare various energy levels under static and dynamic conditions. A glass tube was inserted into the liver tissue and filled with water. DAwas then located at the center of the glass tube to deliver laser light in the radial direction, leading to cylindrical ablation of the liver tissue. After irradiation of 532 nm at 20 W, ablation length and depth were assessed. The extent of the coagulated region was increased with the irradiation time in both static/multiple and dynamic conditions. Dynamic condition showed the maximum ablation length after irradiation at 20 W for 20 s. All the ablation depths were found in the range of 2.0 ~ 2.5 mm, except the 20W for 15 s in the static condition. The current study confirmed that balloon-assisted cylindrical laser ablation can regulate the ablation region by adjusting treatment conditions depending on the extent of the stricture. Further in vivo studies will be investigated to assess current findings in terms of acute and chronic responses for clinical translation.
Cervical cancer is a fatal disease with over 50% of modality rate. Although chemo and external beam (EB) radiation are used for cancer treatment, radiation therapy has a limited effect and toxicity. Interstitial-photodynamic therapy (I-PDT) is a promising method for locally advanced cervical cancer (LACC). However, there are still challenges to reducing the totoxicity of photosensitizer and improving photoactivation. Thus, we propose a sodium copper chlorophyll (SCC), organic compound, as a photosensitizer. The purpose of this study is to investigate the feasibility of SCC as a photosensitizer, and develop an effective LACC treatment through SCC mediated I-PDT. The proposed therapy was evaluated on human cervical carcinoma cells and HeLa xenograft tumor models. After SCC injection (4 μg/ml and 0.1 g/kg), a 405 nm blue light (BL; 800 mW/cm2) was applied using a frontal (EB-PDT) and diffusing (I-PDT) fiber. SCC or BL was hardly cytotoxic (less than 10%) on cancer cells independently, whereas SCC mediated PDT rapidly and strongly reduced the viability. High intensity of ROS was measured within 20 min after treatment. In addition, SCC mediated PDT stimulated the expressions of cleaved caspase 3, 8, and 9 with downregulated pro-caspase. Moreover, the proposed I-PDT decreased tumor size by up to 37% less than EB-PDT with minimal thermal damage around tissue. The current study demonstrated the potential antitumor effect of SCC mediated I-PDT in human cervical carcinoma cell and xenograft tumor model as a result of biocompatible photosensitizer and improved photoactivation. Therefore, SCC mediated I-PDT can warrant an effective treatment of LACC.
A balloon-integrated diffusing applicator has been developed to treat urethral stenosis. To deliver uniform light, the balloon was inflated by inserting water. However, the air trap in the balloon can cause non-uniform ablation in the tissue due to different thermal boundary conditions between air and water. The current study aims to evaluate optical and thermal effects of the air trap on cylindrical laser treatment of urethral stenosis. Although a siginificant decrease of the air volume in the balloon, at least two deflations were required to entail uniform coagulation in a tubular structure and to avoid the unpredictable optical/thermal effects from the air trap.
A diffusing applicator integrated with a balloon catheter has been developed to treat various types of stenosis [1,2]. To deliver uniform laser light to the tubular tissue, the balloon was inflated by inserting water. However, the residual air trapped in the balloon can cause non-uniform ablation in the tissue due to different thermal boundary conditions between air and water. The current study aims to evaluate optical and thermal effects of the air trap on cylindrical laser treatment on the tubular tissue. A balloon-integrated diffusing applicator was fabricated to deliver 532-nm laser light and to expand an ex vivo liver ductal tissue. The balloon was deflated by using a syringe and then inflated with water. Various numbers of deflations were tested for ex vivo experiments using porcine liver duct. For each deflation condition, the 532 nm laser light was delivered to the tissue at 10 W for 45 s. The liver tissue experienced more coagulation near the air trap region than the water-filled region. In spite of a significant decrease of the air volume in the balloon, at least two deflations were required to entail uniform tissue coagulation in a tubular structure and to avoid the unpredictable optical/thermal effects from the air trap. Further in vivo experiments will be performed to evaluate the effect of the air trap on chronic tissue responses after the cylindrical laser treatment for clinical translations.
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