Investigations of Laser-Assisted Renal Denervation for Treatment of Resistant Hypertension.

BACKGROUND AND OBJECTIVES: Renal denervation (RDN) is an emerging surgical treatment for resistant hypertension. However, the current RDN using radiofrequency can cause undesirable thermal damage to the medial and luminal layers due to direct contact between the arterial lumen and energy source. The aim of this study is to evaluate the feasibility of the new laser-assisted RDN by exploring the potential treatment conditions. METHODS: For ex vivo testing, six different treatment conditions (10 and 20 W applied for delivery of 300, 450, and 600 J) were tested on the porcine liver and renal artery (RA) by using a continuous wave 1064 nm laser wavelength. The ablated area in the liver tissue was measured to estimate the extent of the coagulated area. Histological evaluation was performed on the treated RA tissues to confirm the extent of thermal nerve damage. RESULTS: The ablated depth, length, and area in the liver tissue increased with laser power and total energy. According to the histological results, 20 W groups yielded more significant damage to the RA nerves than 10 W groups at the total energy of 300 J (0.0 ± 0.0 mm for 10 W vs. 2.9 ± 1.0 mm for 20 W), 450 J (1.9 ± 0.6 mm for 10 W vs. 6.8 ± 1.5 mm for 20 W), and 600 J (2.9 ± 0.4 mm for 10 W vs. 7.3 ± 0.8 mm for 20 W). The treated RA exhibited insignificant medial injury in depth (medial thinning ≤ 25%), and no difference in the medial thinning was found among the six groups (p = 0.4). CONCLUSION: The current study demonstrated that the 1064 nm laser at 20 W with delivery of 450 J could effectively damage the RA nerves with no or minimal injury to the surrounding tissue. The proposed laser-assisted RDN may enhance physiological effects with insignificant complications in in vivo situations. Further in vivo studies will be conducted to validate the current findings by evaluating the extent of blood pressure reduction and norepinephrine changes after the laser-assisted RDN on a large animal model.

Investigation of photothermal treatment with 532 nm laser light on laryngeal cancer in an in vivo tumor model.

Laryngeal cancer is the second most common cancer in the upper aerodigestive tract, with its incidence increasing across all ages. The conventional treatments for laryngeal cancer include surgical procedure, radiation, and chemotherapy; however, these treatments can lead to various complications. Photothermal therapy (PTT) using laser light has been employed form cancer effective treatment because of its minimal invasion and short operation time. The current study aims to investigate the feasibility of 532 nm PTT on laryngeal cancer in an invivo tumor model. Ex vivo dosimetry evaluation was conducted to determine the laser irradiation conditions, and HEP-2 tumor bearing mice were used to demonstrate in vivo photothermal effects. In addition, histology and western blot analysis were conducted to verify tumor necrosis and any changes in cancer-associated factors in the tumor tissues. The current in vivo results showed that PTT at 5 W for 40 s and 20 W for 10 s had comparable effects in terms of temperature increase and tumor removal. The 532 nm PTT significantly decreased the remaining tumor and downregulated the expression levels of MMP- 9 and ERK. The current study demonstrated that the 532 nm PTT could be a feasible option for treatment of laryngeal tumor with high power delivery for a short exposure time. Further investigations will confirm the endoscopic application of the 532 nm PTT for the treatment of intralaryngeal tissue prior to clinical translation.

Comparative efficacies and safeties of cylindrical interstitial laser ablation and radiofrequency ablation on swine pancreas.

Laser ablation (LA) has been evaluated for the minimally invasive thermal treatment of various cancers, but conventional unidirectional endoscopic ultrasound (EUS)-guided LA has limitations. Therefore, we developed a cylindrical laser diffuser to overcome the limitations of unidirectional EUS-guided LA. The purpose of this study was to compare the efficacies and safeties of EUS-guided LA using a novel cylindrical laser diffuser and radiofrequency ablation (RFA) in vivo in swine pancreas. EUS-guided RFA (15 W, 30 s, 450 J) and cylindrical interstitial LA (CILA) (5 W, 90 s, 450 J) were applied to normal pancreatic tissue in six anesthetized pigs (three per group). Laboratory tests were performed at baseline, immediately after ablation (day 0), and 2 days after procedures (day 2). Two days after procedures, all pigs were sacrificed, and histopathological safety and efficacy assessments were performed. Technically, EUS-guided RFA and CILA were performed successfully in all cases. No major complications, including perforation or acute pancreatitis, occurred during the experiment in either group. All animals remained in excellent condition throughout the experimental period, and laboratory tests provided no evidence of a major complication. Average necrotic volumes in the RFA and CILA groups were 424.2 mm3 and 3747.4 mm3, respectively, and average necrotic volume was significantly larger in CILA group (p < 0.001). EUS-guided RFA and CILA had acceptable safety profiles in the normal swine pancreas model. Our findings indicate EUS-guided CILA has potential for the effective local treatment of pancreatic cancer as an alternative to EUS-guided RFA.

Balloon-assisted laser application for endoscopic treatment of biliary stricture.

OBJECTIVES: Malignant biliary stricture is a ductal narrowing of the bile duct that is often diagnosed at an advanced stage, leading to difficulty in resection. The current study aims to evaluate the feasibility of endobiliary laser treatment by quantifying the extent of coagulative necrosis in tissue under various conditions. METHODS: Ex vivo and in vivo porcine bile tissues were used for endobiliary laser treatment to characterize the dosimetric responses of the tissue to various treatment conditions: power level, irradiation time, and number of treatments. 532 nm laser light was coupled with a balloon-integrated diffusing applicator (BDA) to deliver the laser light endoscopically for tissue coagulation. The coagulated regions (maximum length and depth) in the treated tissues were evaluated histologically for quantitative comparison. RESULTS: Dosimetric evaluations with ex vivo liver tissue confirmed that both maximum length and depth of coagulative necrosis (CN) increased with applied power and number of treatments. Ex vivo bile duct tests demonstrated that BDA-assisted laser treatment at 10 W for 12 s reproducibly yielded CN with a length of 5.8 ± 1.6 mm and a depth of 0.6 ± 0.2 mm. In vivo tests presented that endoscopic laser treatment using the BDA created CN on the ductal surface without any perforation. Microscopic examinations revealed that a dense inflammatory cell infiltration and eosinophilic area in the in vivo treated tissue. The extent of CN in the in vivo tissue was 40% longer and 120% deeper (length: 8.1 ± 0.7 mm; depth: 1.3 ± 0.2 mm), compared to that in the ex vivo tissue. CONCLUSION: BDA-assisted laser treatment could be a feasible option for endoscopic treatment of biliary stricture with uniform ablation at the circumference of bile duct. Further in vivo studies will be performed in a large number of stricture-developed porcine models to examine both efficacy and safety of the proposed endobiliary laser treatment for clinical translations.

Comparative Evaluations on Real-Time Monitoring of Temperature Sensors during Endoscopic Laser Application.

Temperature sensors, such as Fiber Bragg Grating (FBG) and thermocouple (TC), have been widely used for monitoring the interstitial tissue temperature during laser irradiation. The aim of the current study was to compare the performance of both FBG and TC in real-time temperature monitoring during endoscopic and circumferential laser treatment on tubular tissue structure. A 600-µm core-diameter diffusing applicator was employed to deliver 980-nm laser light (30 W for 90 s) circumferentially for quantitative evaluation. The tip of the TC was covered with a white tube (W-TC) in order to prevent direct light absorption and to minimize temperature overestimation. The temperature measurements in air demonstrated that the measurement difference in the temperature elevations was around 3.5 °C between FBG and W-TC. Ex vivo porcine liver tests confirmed that the measurement difference became lower (less than 1 °C). Ex vivo porcine esophageal tissue using a balloon-integrated catheter exhibited that both FBG and W-TC consistently showed a comparable trend of temperature measurements during laser irradiation (~2 °C). The current study demonstrated that the white tube-covered TC could be a feasible sensor to monitor interstitial tissue temperature with minimal overestimation during endoscopic laser irradiation. Further in vivo studies on gastroesophageal reflux disease will investigate the performance of the W-TC to monitor the temperature of the esophageal mucosa surface in real-time mode to warrant the safety of endoscopic laser treatment.

Anti-Cancer Effect of Chlorophyllin-Assisted Photodynamic Therapy to Induce Apoptosis through Oxidative Stress on Human Cervical Cancer.

Photodynamic therapy is an alternative approach to treating tumors that utilizes photochemical reactions between a photosensitizer and laser irradiation for the generation of reactive oxygen species. Currently, natural photosensitive compounds are being promised to replace synthetic photosensitizers used in photodynamic therapy because of their low toxicity, lesser side effects, and high solubility in water. Therefore, the present study investigated the anti-cancer efficacy of chlorophyllin-assisted photodynamic therapy on human cervical cancer by inducing apoptotic response through oxidative stress. The chlorophyllin-assisted photodynamic therapy significantly induced cytotoxicity, and the optimal conditions were determined based on the results, including laser irradiation time, laser power density, and chlorophyllin concentration. In addition, reactive oxygen species generation and Annexin V expression level were detected on the photodynamic reaction-treated HeLa cells under the optimized conditions to evaluate apoptosis using a fluorescence microscope. In the Western blotting analysis, the photodynamic therapy group showed the increased protein expression level of the cleaved caspase 8, caspase 9, Bax, and cytochrome C, and the suppressed protein expression level of Bcl-2, pro-caspase 8, and pro-caspase 9. Moreover, the proposed photodynamic therapy downregulated the phosphorylation of AKT1 in the HeLa cells. Therefore, our results suggest that the chlorophyllin-assisted photodynamic therapy has potential as an antitumor therapy for cervical cancer.

Enhancement of gold nanorods-assisted photothermal treatment on cancer with laser power in stepwise modulation.

OBJECTIVES: Photothermal therapy (PTT) is a minimally invasive or noninvasive method by destructing cancer cells through selective thermal decomposition. However, a long period of laser irradiation to achieve coagulative necrosis often causes unfavorable thermal damage to the surrounding healthy tissue. The current study aims to evaluate the feasibility of temporal power modulation to improve the treatment efficacy of gold nanorods-assisted PTT against tumor tissue. MATERIALS AND METHODS: A total of 25 µg/ml of PEGylated gold nanorods (PEG-GNR) was used as an absorbing agent during 1064 nm laser irradiation for PTT. Temperature monitoring was conducted on the aqueous solution of PEG-GNR for dosimetry comparison. For in vivo tests, CT-26 tumor-bearing murine models with PEG-GNR injected were treated with three irradiation conditions: 3 W/cm2 for 90 s, 1.5 W/cm2 for 180 s, and 3 W/cm2 for 60 s followed by 1.5 W/cm2 for 60 s (modulated). Ten days after the treatments, histology analysis was performed to assess the extent of coagulation necrosis in the treated tissues. RESULTS: The temporal power modulation maintained the tissue temperature of around 50°C for a longer period during the irradiation. Histology analysis confirmed that the modulated group entailed a larger coagulative necrosis area with less thermal damage to the peripheral tissue, compared to the other irradiation conditions. CONCLUSION: Therefore, the power-modulated PTT could improve treatment efficacy with reduced injury by maintaining the constant tissue temperature. Further studies will examine the feasibility of the proposed technique in large animal models in terms of acute and chronic tissue responses and treatment margin for clinical translations.

Impact of residual air trap in balloon on laser treatment of tubular tissue.

OBJECTIVES: Tubular tissue, such as the bile duct and esophagus, often suffers from stenosis due to chronic inflammation or excessive contraction of smooth muscle. Laser treatment using a balloon catheter has been used to treat tubular tissue stenosis by mechanically expanding the tissue and irradiating laser light circumferentially on the tissue lumen. As the balloon is inflated with saline, the residual air in a delivery channel is often accumulated in the inflated balloon. Thus, the air trap may cause physical discontinuities at air-saline interface, leading to unpredictable and nonuniform photothermal interactions. The aim of the current study was to evaluate the optical-thermal effects of the air trap in the balloon on laser treatment of the tubular tissue by means of numerical simulations and experimental validations. MATERIALS AND METHODS: A balloon-assisted diffusing applicator (BDA) was developed to inflate a balloon and deliver uniform and circumferential laser light. Before the balloon inflation, various numbers of deflations (0, 1, 2, 3, and 4) were applied to estimate the average amount of the air removed from the balloon. Ex vivo experiments using porcine liver duct were conducted with two deflation conditions (D0: no deflation for air trap and D3: three deflations for no air trap). The balloon was horizontally situated during laser irradiation to maintain the air trap at the same position in the balloon by minimizing gravity effect. Upon balloon inflation, 532 nm laser light was delivered through the BDA to the tissue (irradiance = 4 W/cm2 ) at 10 W for 45 seconds to assess the optical-thermal effects of the air trap on the ductal tissue. RESULTS: The size of the air trap was noticeably reduced with the number of deflations. The air trap volume in the balloon decreased to 0.5% of the total balloon volume after D3. Ex vivo results demonstrated that thicker coagulative necrosis (CN) for D0 near the air trap region in the tissue than bottom region that contact with saline, representing an asymmetric profile of CN in the tissue. D0 generated 17% thicker and nonuniform CN (overall CN thickness = 1.4 ± 0.7 mm), compared with D3 with no air trap (overall CN thickness = 1.2 ± 0.2 mm; p < 0.05). A threefold larger eccentricity (E) was found in D0 (49 ± 31%) than D3 (15 ± 13%; p < 0.001). CONCLUSION: Both numerical simulations and experiments validated the effect of the air trap in a balloon on the distribution of CN in a tubular tissue during BDA-assisted laser treatment. Further in vivo studies will assess the current findings on the air trap for clinical translations of BDA-assisted laser treatment of tubular tissue stenosis.

Marine Biological Macromolecules and Chemically Modified Macromolecules; Potential Anticoagulants.

Coagulation is a potential defense mechanism that involves activating a series of zymogens to convert soluble fibrinogen to insoluble fibrin clots to prevent bleeding and hemorrhagic complications. To prevent the extra formation and diffusion of clots, the counterbalance inhibitory mechanism is activated at levels of the coagulation pathway. Contrariwise, this system can evade normal control due to either inherited or acquired defects or aging which leads to unusual clots formation. The abnormal formations and deposition of excess fibrin trigger serious arterial and cardiovascular diseases. Although heparin and heparin-based anticoagulants are a widely prescribed class of anticoagulants, the clinical use of heparin has limitations due to the unpredictable anticoagulation, risk of bleeding, and other complications. Hence, significant interest has been established over the years to investigate alternative therapeutic anticoagulants from natural sources, especially from marine sources with good safety and potency due to their unique chemical structure and biological activity. This review summarizes the coagulation cascade and potential macromolecular anticoagulants derived from marine flora and fauna.

Laser ablation of pancreatic cancer using a cylindrical light diffuser.

Pancreatic cancer (PC) is a leading cause of cancer death and its incidence and mortality have shown an increasing trend. Despite improvements in outcomes, another treatment option is required for PC. Laser ablation (LA) has been evaluated for the treatment of various types of cancer. The aim of this study was to assess the safety and feasibility of a novel cylindrical light diffuser in a xenograft model of PC. This study was performed using a customized high-power laser system. PANC-1 cells and BALB/c mice were used for experiments at a laser power of 5 W for 40 to 200 s at five different energy levels (n = 30). There was no acute bleeding or major complication. Using the cylindrical light diffuser, tumors were irradiated with similar size in each energy group. A correlation between laser dose and tumor necrosis was observed. Pearson's correlation for the relation between the amount of necrosis area and laser ablation energy on day 3 was 0.78 (p < 0.01). No statistical difference of necrosis area was exhibited when the necrosis area of each harvested tumor analyzed by dividing into 5 specimens for each energy. The study demonstrates that LA treatment using a cylindrical light diffuser induced remarkable tumor necrosis at histopathologic examinations. Laser ablation dosage and tumor response were strongly correlated, and the ablation procedure resulted in homogeneous tissue necrosis. No adverse event was encountered. These findings suggest that the devised cylindrical light diffuser offers a safe and effective means of treating pancreatic cancer.

Postoperative Angular Changes According to Weightbearing in Patients With Moderate to Severe Hallux Valgus.

Hallux valgus is a progressive angular deformity of the big toe, the degree of which is aggravated in weightbearing stance. Hallux valgus and intermetatarsal angles on postoperative weightbearing images are usually larger than those of intraoperative fluoroscopic and immediate postoperative non-weightbearing images. Here, we hypothesized that various angular parameters of hallux valgus would increase postoperatively with weightbearing. A total of 66 feet (58 patients) of moderate to severe hallux valgus were reviewed on consecutive plain foot anteroposterior radiographs. The changes of hallux valgus, intermetatarsal, hallux valgus interphalangeal, and distal metatarsal articular angles were compared. Hallux valgus and intermetatarsal angles were significantly increased with weightbearing postoperatively (p < .001). Hallux valgus interphalangeal and distal metatarsal articular angles did not show significant changes with weightbearing (p > .5). Hallux valgus and intermetatarsal angles were increased with weightbearing after hallux valgus surgery. Mean angular changes were 5.3 and 2.7 degrees, respectively. These values should be considered in the preoperative planning and intraoperative correction processes.

High-performance coaxial piezoelectric energy generator (C-PEG) yarn of Cu/PVDF-TrFE/PDMS/Nylon/Ag.

Coaxial type piezoelectric energy generator (C-PEG) nanofiber was fabricated by a self-designed continuous electrospinning deposition system. Piezoelectric PVDF-TrFE nanofiber as an electroactive material was electrospun at a discharge voltage of 9-12 kV onto a simultaneously rotating and transverse moving Cu metal wire at an angular velocity of ω g = 60-120 RPM. The piezoelectric coefficient d33 of the PVDF-TrFE nanofiber was approximately -20 pm V-1. The generated output voltage (V G) increased according to the relationship exp(-α P) (α = 0.41- 0.57) as the pressure (P) increased from 30 to 500 kpa. The V G values for ten and twenty pieces of C-PEG were V G = 3.9 V and 9.5 V at P = 100 kpa, respectively, relatively high output voltages compared to previously reported values. The high V G for the C-PEG stems from the fact that it can generate a fairly high V G due to the increased number of voltage collection points compared to a conventional two-dimensional (2-dim) capacitor type of piezoelectric film or fiber device. C-PEG yarn was also fabricated via the dip-coating of a PDMS polymer solution, followed by winding with Ag-coated nylon fiber as an outer electrode. The current and power density of ten pieces of C-PEG yarn were correspondingly 22 nA cm-2 and 8.6 µW cm-3 at V G = 1.97 V, higher than previously reported values of 5.54 and 6 µW cm-3. The C-PEG yarn, which can generate high voltage compared to the conventional film/nanofiber mat type, is expected to be very useful as a wearable energy generator system.

Multiple cylindrical interstitial laser ablations (CILAs) of porcine pancreas in ex vivo and in vivo models.

BACKGROUND: The therapeutic capacity of multiple cylindrical interstitial laser ablations (CILAs) of pancreatic tissue was evaluated with 1064 nm laser light in ex vivo and in vivo porcine pancreatic models. METHODS: A diffusing applicator was sequentially employed to deliver 1064 nm laser light in a cylindrical distribution to ablate a large volume of pancreatic tissue. Ex vivo tissue was tested at various power levels (5, 7, and 10 W) under US imaging. An in vivo porcine model was used to evaluate the clinical feasibility of multiple CILAs on pancreatic tissue at 5 W via laparotomy (N = 3). RESULTS: Multiple CILAs symmetrically ablated a range of ex vivo tissue volumes (2.4-6.0 cm3) at various power levels. Multiple CILAs warranted a therapeutic capacity of symmetrically ablating in vivo pancreatic tissue. Both ex vivo and in vivo pancreatic tissues after multiple CILAs at 5 W confirmed the absence of or minimal thermal injury to the peripheral tissue and carbonization. CONCLUSIONS: The current findings suggest that the collective thermal effects from multiple CILAs can help widely ablate pancreatic tissue with minimal thermal injury. Further in vivo studies will investigate the safety of the proposed CILA treatment as well as acute/chronic responses of pancreatic tissue for clinical translations.

Phloroglucinol-Gold and -Zinc Oxide Nanoparticles: Antibiofilm and Antivirulence Activities towards Pseudomonasaeruginosa PAO1.

With the advancement of nanotechnology, several nanoparticles have been synthesized as antimicrobial agents by utilizing biologically derived materials. In most cases, the materials used for the synthesis of nanoparticles from natural sources are extracts. Natural extracts contain a wide range of bioactive components, making it difficult to pinpoint the exact component responsible for nanoparticle synthesis. Furthermore, the bioactive component present in the extract changes according to numerous environmental factors. As a result, the current work intended to synthesize gold (AuNPs) and zinc oxide (ZnONPs) nanoparticles using pure phloroglucinol (PG). The synthesized PG-AuNPs and PG-ZnONPs were characterized using a UV-Vis absorption spectrophotometer, FTIR, DLS, FE-TEM, zeta potential, EDS, and energy-dispersive X-ray diffraction. The characterized PG-AuNPs and PG-ZnONPs have been employed to combat the pathogenesis of Pseudomonas aeruginosa. P. aeruginosa is recognized as one of the most prevalent pathogens responsible for the common cause of nosocomial infection in humans. Antimicrobial resistance in P. aeruginosa has been linked to the development of recalcitrant phenotypic characteristics, such as biofilm, which has been identified as one of the major obstacles to antimicrobial therapy. Furthermore, P. aeruginosa generates various virulence factors that are a major cause of chronic infection. These PG-AuNPs and PG-ZnONPs significantly inhibit early stage biofilm and eradicate mature biofilm. Furthermore, these NPs reduce P. aeruginosa virulence factors such as pyoverdine, pyocyanin, protease, rhamnolipid, and hemolytic capabilities. In addition, these NPs significantly reduce P. aeruginosa swarming, swimming, and twitching motility. PG-AuNPs and PG-ZnONPs can be used as control agents for infections caused by the biofilm-forming human pathogenic bacterium P. aeruginosa.

In vitro anti-tumor effect of high-fluence low-power laser light on apoptosis of human colorectal cancer cells.

Colorectal cancer is the third most common malignancy all over the world, along with high morbidity and mortality. As a treatment, high-fluence low-power laser irradiation (HF-LPLI) has reported that its biostimulatory activity can suppress or even destruct tumor growth in neoplastic diseases. The aim of the present study is to examine a therapeutic capacity of HF-LPLI for colorectal cancer treatment by using human colon cancer cell (HT29) model. The in vitro cancer cell model was used to analyze the underlying mechanism of laser-induced apoptosis. Laser irradiation was performed five times (once a day for five consecutive days) with 635 nm laser light for 8 and 16 min (fluence = 128 and 256 J/cm2), respectively. The efficiency of the HF-LPLI treatment was evaluated by MTT, fluorescence staining, cell wound healing, and western blot test during the 5-day period. Experiment data showed that HF-LPLI had a dose-dependent stimulating effect on cell viability, migration, and apoptosis of HT29 cells. The inhibition effect of laser treatment at 256 J/cm2 on cell viability was statistically significant. Meanwhile, the wound healing and western blot tests also confirmed that HF-LPLI could inhibit cell migration and induce cell apoptosis. The current research results demonstrate that 635 nm HF-LPLI can be an alternative treatment option for colorectal cancer by increasing the expression of caspase-3 and inducing HT29 tumor cell apoptosis through activation of the mitochondrial pathway.

Evaluations on laser ablation of ex vivo porcine stomach tissue for development of Ho:YAG-assisted endoscopic submucosal dissection (ESD).

Endoscopic submucosal dissection (ESD) is clinically used to remove early gastric cancer in stomach. The aim of the current study is to examine a therapeutic capacity of pulsed Ho:YAG laser for the development of laser-assisted ESD under various surgical parameters. Ex vivo porcine stomach tissue was ablated with 1-J Ho:YAG pulses at 10 Hz at different number of treatments (NT = 1, 2, and 3) and treatment speeds (TS = 0.5, 1, and 2 mm/s) without and with saline injection. Regardless of saline injection, straight tissue ablation showed that ablation depth increased with increasing NT and decreasing TS. At NT = 3 and TS = 0.5 mm/s, no saline injection yielded the maximum ablation depth (3.4 ± 0.3 mm), partially removing muscularis propria. However, saline injection confined the tissue ablation within a submucosal layer (2.1 ± 0.3 mm). Thermal injury was found to be 0.7~1.1 mm in the adjacent tissue with superficial carbonization. Circular tissue ablation (2 cm in diameter) at NT = 3 and TS = 0.5 mm/s presented that no saline injection yielded a reduction in the lesion area, whereas saline injection maintained the ablated lesion area. Histological analysis revealed that unlike no saline injection, saline injection ablated the entire mucosal layer without perforation in the muscular propria. The pulsed Ho:YAG laser can be a potential surgical tool for clinical ESD to incise a target lesion without adverse perforation. Further investigations will validate the efficacy and safety of the Ho:YAG laser-assisted ESD in in vivo porcine stomach models for clinical translation.

The use of a 532-nm laser fitted with a balloon and a cylindrical light diffuser to treat benign biliary stricture: a pilot study.

Endoscopic management of benign biliary stricture (BBS) remains challenging. Stenting is currently used for BBS management, but refractory BBS remains problematic. The aim of this study was to assess the safety and feasibility of a dilation balloon-equipped cylindrical light diffuser for BBS in a large animal model. A total of seven mini-pigs were used in the current study. Laser settings were chosen based on the findings of a previous animal study. Five animals were used in a preliminary study to establish process conditions. BBSs were created in the common bile ducts of the other two animals by intraductal radiofrequency ablation (RFA) via endoscopic retrograde cholangiography (ERC). At 4 weeks post-RFA, laser ablation was performed using a customized balloon-equipped cylindrical diffuser at 10 W for 10 s while maintaining balloon inflation for 10 s at 5 atm. A follow-up ERC was performed at 4 weeks post-laser ablation and the animals were sacrificed for histologic evaluation. BBS was observed in all animals by ERC at 4 weeks post-RFA. The mean bile duct stricture diameter in the two animals as determined by ERC was 0.8 mm. Laser ablations were performed without technical difficulty and no adverse event was encountered. At 4 weeks post-laser ablation, mean biliary stricture diameter had dilated to 1.6 mm on cholangiographic finding. On histologic examination, inflammatory cell infiltration in lamina propria and dense collagen deposition were observed, but there was no evidence of bile duct perforation. The devised balloon-equipped cylindrical laser light diffuser appears to be safe and feasible for the treatment of BBS. However, further studies and modifications are required before it can be applied clinically as a monotherapy.

Dependence of laser-induced tissue ablation on optical fiber movements for laser prostatectomy.

PURPOSE: The aim of the current study was to identify the efficient fiber movements for 532-nm laser prostatectomy. MATERIALS AND METHODS: 532-nm Lithium triborate (LBO) laser light was tested on 120 kidney tissues at three different translational speeds (TS 1, 2, and 4 mm/s) and four different rotational speeds (RS 0.5, 1.0, 1.6, and 2.1 rad/s). The applied power was 120 W at a 2-mm working distance and 60° sweeping angle. Ablation rate and dimensions of resulting ablation craters were measured. RESULTS: Slower TSs and RSs created deeper and wider ablation craters with thinner coagulation, leading to more efficient ablation performance. Maximal ablation rate was achieved at a TS of 2 mm/s and RSs of 0.5 and 1.0 rad/s. An RS of 0.5 rad/s accompanied surface carbonization for all the TSs. Irrespective of TS, ablation rate became saturated at faster RSs than 1.0 rad/s. Faster TSs or RSs reduced tissue ablation, but increased thermal coagulation due to a shorter interaction time. CONCLUSIONS: Optimal ablation efficiency occurred at a TS of 2 mm/s and a RS of 1.0 rad/s with a thin coagulation of around 1.0 mm and no or minimal carbonization. Further studies will validate the current findings with prostate tissue and high-power levels for laser prostatectomy.

Combined treatment of low-level laser therapy and phloroglucinol for inhibition of fibrosis.

BACKGROUND AND OBJECTIVES: Fibrosis is a highly prevalent disease, which is responsible for 45% of deaths through pathological effects in developed countries. Previous studies have reported that low-level laser therapy (LLLT) can modulate fibrotic activity, but significant enhancement of therapeutic efficacy is still required for clinical translation. The aim of this study is to evaluate the feasible effect of LLLT combined with phloroglucinol (PHL) on the inhibition of fibrosis in vitro. STUDY DESIGN/MATERIALS AND METHODS: NIH/3T3 murine embryonic fibroblasts cells were cultured and transforming growth factor-ß1 (TGF-ß1) was treated for transition of fibroblasts. After TGF-ß1 treatment, LLLT and PHL were used, respectively, and in combination to suppress fibrosis. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and BrdU assays were performed to estimate the cell viability and proliferation. To evaluate the expression of fibrotic markers, we used confocal immunofluorescence and western blot. RESULTS: When compared with respectively treated groups, the group with the combined treatment of LLLT and PHL significantly reduced cell viability and proliferation. Immunofluorescence staining showed that the combined group minimized more α-smooth muscle actin (α-SMA) and type I collagen than the other groups. Western blot analysis showed that the combined treatment had significant decreases in α-SMA, TGF-ß1, and type I collagen. CONCLUSIONS: PHL-assisted LLLT may be an effective treatment to inhibit fibrosis due to its additive effects. The combined treatment has a potential to be an alternative treatment for fibrosis. Lasers Surg. Med. © 2019 Wiley Periodicals, Inc.

Application of Ultrasound Thermal Imaging for Monitoring Laser Ablation in Ex Vivo Cardiac Tissue.

BACKGROUND AND OBJECTIVE: Laser ablation can be used to treat atrial fibrillation by thermally isolating pulmonary veins. In this study, we evaluated the feasibility of high-resolution (<1 mm) ultrasound thermal imaging to monitor spatial temperature distribution during laser ablation on ex vivo cardiac tissue. STUDY DESIGN/MATERIALS AND METHODS: Laser ablation (808 nm) was performed on five porcine cardiac tissue samples. A thermocouple was used to measure the interstitial tissue temperature during the laser ablation process. Tissue-strain-based ultrasound thermal imaging was conducted to monitor the spatial distribution of the temperature in the cardiac tissue. The tissue temperature was estimated from the time shifts of ultrasound signals owing to the changes in the speed of sound and was compared with the measured temperature. The temperature estimation coefficient k of porcine cardiac tissue was calculated from the estimated thermal strain and the measured temperature. The degree of tissue coagulation (temperatures > 50°C) was derived from the estimated temperature and was compared with that of the tested cardiac tissue. RESULTS: The estimated tissue temperature using strain-based ultrasound thermal imaging at a depth of 1 mm agreed with thermocouple measurements. During the 30-second period of the laser ablation process, the estimated tissue temperature increased from 25 to 70°C at a depth of 0.1 mm, while the estimated temperature at a depth of 1 mm increased up to 46°C. Owing to the uncertainty of the coefficient k, the k value of the porcine cardiac tissue varied from 160 to 220°C with temperature changes of up to 20°C. The estimated coagulation region in the ultrasound thermal imaging was 20% wider (+0.6 mm) but 9% shallower (-0.1 mm) than the measured region of the ablated porcine cardiac tissue. CONCLUSIONS: The current study demonstrated the feasibility of temperature monitoring with the use of ultrasound thermal imaging during the laser ablation on ex vivo porcine cardiac tissue. The high-resolution ultrasound thermal imaging could map the spatial distribution of the tissue temperature. The proposed method can be used to monitor the temperature and thermal coagulation to achieve effective laser ablation for atrial fibrillation. Lasers Surg. Med. © 2019 Wiley Periodicals, Inc.