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.

Risk factors of revision operation and early revision for adjacent segment degeneration after lumbar fusion surgery: a case-control study.

BACKGROUND CONTEXT: Adjacent segment degeneration (ASD) following lumbar fusion operation is common and can occur at varying timepoints after index surgery. An early revision operation for ASD, however, signifies a short symptom-free period and might increase the risk of successive surgeries. PURPOSE: We aimed to elucidate the overall risk factors associated with revision surgeries for ASD with distinct attention to early revisions. STUDY DESIGN/SETTING: Retrospective, case-control study. PATIENT SAMPLE: The study included 86 patients who underwent revision operations for ASD after lumbar fusion in the revision group and 166 patients who did not for at least 5 years after index surgery. OUTCOME MEASURES: Sagittal parameters, Pfirrmann grading, facet degeneration grading, and disc space height (DSH) of adjacent segments were assessed. METHODS: Revision operations within 5 years postsurgery were defined as early revision. We compared the revision and no-revision groups as well as the early- and late-revision groups. RESULTS: The revision group demonstrated a significantly greater preoperative C7-S1 sagittal vertical axis (SVA) (p=.001), postoperative C7-S1 SVA (p<.001), and postoperative pelvic incidence (PI)-lumbar lordosis (LL) (p<.001) than those in the no-revision group. Preoperative DSH of the proximal adjunct segment (p=.001), postoperative PI-LL (p=.014), and postoperative C7-S1 SVA (p=.037) exhibited significant association with ASD in logistic regression analysis. The early-revision group had a significantly higher patient age (p=.001) and a greater number of levels fused (p=.030) than those in the late-revision group. Multivariate Cox regression analysis demonstrated that old age (p=.045), a significant number of levels fused (p=.047), and a narrow preoperative DSH of the proximal adjacent level (p=.011) were risk factors for early revision. CONCLUSIONS: Postoperative sagittal imbalance, including significant PI-LL and C7-S1 SVA were risk factors for revision operation for ASD but not for early revision. These factors are likely to affect the long-term risk of revision operation due to ASD and thus are not considered risk factors for early revision. Narrow DSH of the proximal adjacent level increased the risks of both revision and early revision surgeries. Moreover, old age and a significant number of levels fused further increased the risk for early revision for ASD.

Photo-triggered caffeic acid delivery via psyllium polysaccharide- gellan gum-based injectable bionanogel for epidermoid carcinoma treatment.

Here, the simultaneous effect of chemo- and photothermal therapy against epidermoid carcinoma (EC) was investigated. A novel hydrogel, termed bionanogel (BNG), was designed using psyllium mucilage polysaccharide and bacterial gellan gum, incorporated with nanocomplex carrying caffeic acid (CA) and IR-820, and further characterized. The dual effect of BNG and 808 nm laser (BNG + L) on EC was investigated. Staining and scratch assays were performed to analyze their therapeutic effect on EC. In vivo evaluations of BNG + L in xenograft models were performed. Rapid transition, limited swelling, degradability and high tensile strength indicated BNG stability and sustained drug release. Irradiation with 808 nm laser light at 1.25 W /cm2 for 4 min resulted in a temperature increase of 53 °C and facilitated cell ablation. The in vitro studies showed that BNG + L suppressed cancer progression via a late apoptotic effect. The in vivo study showed that the slow release of CA from BNG + L significantly attenuated EC with low mitotic index and downregulation of proteins involved in cancer proliferation such as EGFR, AKT, PI3K, ERK, mTOR and HIF-1α. Thus, BNG could be a novel medium for targeted and controlled drug delivery for the treatment of epidermoid cancer when triggered by NIR light.

A long-term storable gel-laden chip composite built in a multi-well plate enablingin situcell encapsulation for high-throughput liver model.

Hydrogels are widely used as scaffold materials for constructingin vitrothree-dimensional microphysiological systems. However, their high sensitivity to various external cues hinders the development of hydrogel-laden, microscale, and high-throughput chips. Here, we have developed a long-term storable gel-laden chip composite built in a multi-well plate, which enablesin situcell encapsulation and facilitates high-throughput analysis. Through optimized chemical crosslinking and freeze-drying method (C/FD), we have achieved a high-quality of gel-laden chip composite with excellent transparency, uniform porosity, and appropriate swelling and mechanical characteristics. Besides collagen, decellularized extracellular matrix with tissue-specific biochemical compound has been applied as chip composite. As a ready-to-use platform,in situcell encapsulation within the gel has been achieved through capillary force generated during gel reswelling. The liver-mimetic chip composite, comprising HepG2 cells or primary hepatocytes, has demonstrated favorable hepatic functionality and high sensitivity in drug testing. The developed fabrication process with improved stability of gels and storability allows chip composites to be stored at a wide range of temperatures for up to 28 d without any deformation, demonstrating off-the-shelf products. Consequently, this provides an exceptionally simple and long-term storable platform that can be utilized for an efficient tissue-specific modeling and various biomedical applications.

Local dose-dense chemotherapy for triple-negative breast cancer via minimally invasive implantation of 3D printed devices.

Dose-dense chemotherapy is the preferred first-line therapy for triple-negative breast cancer (TNBC), a highly aggressive disease with a poor prognosis. This treatment uses the same drug doses as conventional chemotherapy but with shorter dosing intervals, allowing for promising clinical outcomes with intensive treatment. However, the frequent systemic administration used for this treatment results in systemic toxicity and low patient compliance, limiting therapeutic efficacy and clinical benefit. Here, we report local dose-dense chemotherapy to treat TNBC by implanting 3D printed devices with time-programmed pulsatile release profiles. The implantable device can control the time between drug releases based on its internal microstructure design, which can be used to control dose density. The device is made of biodegradable materials for clinical convenience and designed for minimally invasive implantation via a trocar. Dose density variation of local chemotherapy using programmable release enhances anti-cancer effects in vitro and in vivo. Under the same dose density conditions, device-based chemotherapy shows a higher anti-cancer effect and less toxic response than intratumoral injection. We demonstrate local chemotherapy utilizing the implantable device that simulates the drug dose, number of releases, and treatment duration of the dose-dense AC (doxorubicin and cyclophosphamide) regimen preferred for TNBC treatment. Dose density modulation inhibits tumor growth, metastasis, and the expression of drug resistance-related proteins, including p-glycoprotein and breast cancer resistance protein. To the best of our knowledge, local dose-dense chemotherapy has not been reported, and our strategy can be expected to be utilized as a novel alternative to conventional therapies and improve anti-cancer efficiency.

A literature review of bioactive substances for the treatment of periodontitis: In vitro, in vivo and clinical studies.

Periodontitis is a common chronic inflammatory disease of the supporting tissues of the tooth that involves a complex interaction of microorganisms and various cell lines around the infected site. To prevent and treat this disease, several options are available, such as scaling, root planning, antibiotic treatment, and dental surgeries, depending on the stage of the disease. However, these treatments can have various side effects, including additional inflammatory responses, chronic wounds, and the need for secondary surgery. Consequently, numerous studies have focused on developing new therapeutic agents for more effective periodontitis treatment. This review explores the latest trends in bioactive substances with therapeutic effects for periodontitis using various search engines. Therefore, this study aimed to suggest effective directions for therapeutic approaches. Additionally, we provide a summary of the current applications and underlying mechanisms of bioactive substances, which can serve as a reference for the development of periodontitis treatments.

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.

3D Bioprinted Liver-on-a-Chip for Drug Cytotoxicity Screening.

Tissues on a chip are sophisticated three-dimensional (3D) in vitro microphysiological systems designed to replicate human tissue conditions within dynamic physicochemical environments. However, the current fabrication methods for tissue spheroids on a chip require multiple parts and manual processing steps, including the deposition of spheroids onto prefabricated "chips." These challenges also lead to limitations regarding scalability and reproducibility. To overcome these challenges, we employed 3D printing techniques to automate the fabrication process of tissue spheroids on a chip. This allowed the simultaneous high-throughput printing of human liver spheroids and their surrounding polymeric flow chamber "chips" containing inner channels in a single step. The fabricated liver tissue spheroids on a liver-on-a-chip (LOC) were subsequently subjected to dynamic culturing by a peristaltic pump, enabling assessment of cell viability and metabolic activities. The 3D printed liver spheroids within the printed chips demonstrated high cell viability (>80%), increased spheroid size, and consistent adenosine triphosphate (ATP) activity and albumin production for up to 14 days. Furthermore, we conducted a study on the effects of acetaminophen (APAP), a nonsteroidal anti-inflammatory drug, on the LOC. Comparative analysis revealed a substantial decline in cell viability (<40%), diminished ATP activity, and reduced spheroid size after 7 days of culture within the APAP-treated LOC group, compared to the nontreated groups. These results underscore the potential of 3D bioprinted tissue chips as an advanced in vitro model that holds promise for accurately studying in vivo biological processes, including the assessment of tissue response to administered drugs, in a high-throughput manner.

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.

Effect of dual-optical pulses with temporal energy distribution on laser ablation performance in in vivo zebrafish model.

A Q-switched laser system has been used in a single-pulse mode for skin melasma treatments because of instant heat deposition in the target. Despite the efficient ablation of the melanophores in the skin, the single, high-fluence pulse often causes undesirable damage to the surrounding tissue, leading to high recurrence rates. This study aims to investigate the feasibility of dual-optical pulses with a temporal energy distribution on the melasma treatment in in vivo zebrafish models in comparison to that of the single optical pulse. Based on the optical detection, the dual-optical pulses had a temporal energy distribution ratio of 4:1 and an interval of 61 µs between the two consecutive pulses. According to the histological analysis, the dual pulses removed melanophores and induced a few apoptotic nuclei with minimal recurrence. This study demonstrated that the feasibility of dual-optical pulses (energy ratio = 4:1) could enhance the laser ablation performance in vivo.

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.

Ishophloroglucin A-based multifunctional oxidized alginate/gelatin hydrogel for accelerating wound healing.

This study investigated the potential applicability of wound dressing hydrogels for tissue engineering, focusing on their ability to deliver pharmacological agents and absorb exudates. Specifically, we explored the use of polyphenols, as they have shown promise as bioactive and cross-linking agents in hydrogel fabrication. Ishophloroglucin A (IPA), a polyphenol not previously utilized in tissue engineering, was incorporated as both a drug and cross-linking agent within the hydrogel. We integrated the extracted IPA, obtained through the utilization of separation and purification techniques such as high-performance liquid chromatography (HPLC), liquid chromatography-mass spectrometry (LC-MS), and nuclear magnetic resonance (NMR) into oxidized alginate (OA) and gelatin (GEL) hydrogels. Our findings revealed that the mechanical properties, thermal stability, swelling, and degradation of the multifunctional hydrogel can be modulated via intermolecular interactions between the natural polymer and IPA. Moreover, the controlled release of IPA endows the hydrogel with antioxidant and antimicrobial characteristics. Overall, the wound healing efficacy, based on intermolecular interactions and drug potency, has been substantiated through accelerated wound closure and collagen deposition in an ICR mouse full-thickness wound model. These results suggest that incorporating IPA into natural polymers as both a drug and cross-linking agent has significant implications for tissue engineering applications.

Development of Novel Balloon-Integrated Optical Catheter for Endoscopic and Circumferential Laser Application.

The current study aims to demonstrate the feasibility of a novel balloon-integrated optical catheter (BIOC) to achieve endoscopic laser application for circumferential coagulation of a tubular tissue structure. Both optical and thermal numerical simulations were developed to predict the propagation of laser light and a spatio-temporal distribution of temperature in tissue. Ex vivo esophagus tissue was tested with 980 nm laser light at 30 W for 90 s for quantitative evaluations. In vivo porcine models were used to validate the performance of BIOC for circumferential and endoscopic laser coagulation of esophagus in terms of acute tissue responses post-irradiation. Optical simulations confirmed that a diffusing applicator was able to generate a circumferential light distribution in a tubular tissue structure. Both numerical and experimental results presented that the maximum temperature elevation occurred at 3-5 mm (muscle layer) below the mucosa surface after 90 s irradiation. In vivo tests confirmed the circumferential delivery of laser light to a deep muscle layer as well as no evidence of thermal damage to the esophageal mucosa. The proposed BIOC can be a feasible optical device to provide circumferential laser irradiation as well as endoscopic coagulation of tubular esophagus tissue for clinical applications.

Photomodulative effects of low-level laser therapy on tracheal fenestration developed in in vivo model.

The effect of low-level laser therapy (LLLT) on variable mucosal lesions in the upper aerodigestive tract has been reported. However, the effect of LLLT on tracheostomy sites or tracheal fenestration is rarely reported. In this study, we evaluate the effect of LLLT performed using 635 nm laser light based on a cylindrical diffuser and an animal model with tracheal fenestration. An animal model of tracheal fenestration is developed by suturing the trachea to the skin after performing a vertical tracheostomy from the second to the fifth tracheal ring of Wistar rats (male, body weight 200-250 g). LLLT (spot size: 2 cm2) is conducted once daily for five days using a handheld cylindrical device. Twenty-four rats are randomly assigned to a no-therapy or LLLT group with an energy density of 20 J/cm2. Histological analysis is performed at 7 and 14 days after tracheal fenestration. Irradiation at the tracheal fenestration site with an energy density of 20 J/cm2 improves the wound healing, as shown at 2 weeks after tracheostomy. Histological analysis shows significantly decreased acute inflammation and granulation tissue, as well as better cartilage regeneration and less tracheal wall thickening. Therefore, LLLT demonstrates therapeutic potential for preventing tracheal stenosis and granuloma after tracheostomy.

Cellulose nanofibrils reinforced chitosan-gelatin based hydrogel loaded with nanoemulsion of oregano essential oil for diabetic wound healing assisted by low level laser therapy.

Diabetic foot ulcers are imperfections in the process of wound healing due to hyperglycemic conditions. Here, a nanoemulgel fabricated with oregano essential oil nanoemulsion, assisted by low-level laser therapy, was investigated for its efficacy in diabetic wound healing. A hydrogel- based healing patch, fabricated using biological polymers namely chitosan and gelatin and, polyvinyl pyrollidone. The hydrogel was reinforced with cellulose nanofibrils for enhanced stability and barrier properties. Nanoemulsion of oregano essential oil, with an average particle size of 293.7 ± 8.3 nm, was prepared via homogenization with chitosan as the coating agent. Nanoemulsion impregnated hydrogel, termed as the nanoemulgel, was assessed for its physio-mechanical properties and healing efficiency. The strong linkages in nanoemulgel demonstrated its large swelling capacity, high mechanical strength, and maximum thermal stability. The optimized conditions for low-level laser therapy using 808 nm were 1 W. cm-2 and 5 min. The optimized drug concentration of 128 µg. mL-1 exhibited viability of NIH/3 T3 fibroblasts as 75.5 ± 1.2 % after 24 h. Cell migration assay demonstrated that dual therapy facilitated wound healing, with a maximum closure rate of 100 % at 48 h. In vivo results revealed the rapid healing effects of the dual therapy in diabetic rat models with foot ulcers: a maximum healing rate of 97.5 %, minimum scar formation, increased granulation, enhanced reepithelialization, and a drastic decrease in inflammation and neutrophil infiltration within the treatment period compared to monotherapy and control. In summary, the combinatorial therapy of nanoemulgel and low-level laser therapy is a promising regimen for managing diabetic foot ulcers with a rapid healing effect.

Endoscopic Ultrasound-Guided Pancreatic Interstitial Laser Ablation Using a Cylindrical Laser Diffuser: A Long-Term Follow-Up Study.

BACKGROUND AND AIMS: Local ablative treatment is another option for improving outcomes and has been evaluated for locally advanced pancreatic cancer. We previously suggested endoscopic ultrasound (EUS)-guided interstitial laser ablation using a cylindrical laser diffuser (CILA) might be a feasible therapeutic option based on experiments performed on pancreatic cancer cell lines and porcine model with a short follow-up (3 days). The aim of this study was to investigate the safety of EUS-CILA performed using optimal settings in porcine pancreas with a long-term follow-up (2 weeks). METHODS: EUS-CILA (laser energy of 450 J; 5 W for 90 s) was applied to normal pancreatic tissue in porcine (n = 5) under EUS guidance. Animals were observed clinically for 2 weeks after EUS-CILA to evaluate complications. Computed tomography and laboratory tests were carried out to evaluate safety. Two weeks after EUS-CILA, all pigs were sacrificed, and histopathological safety and efficacy evaluations were conducted. RESULTS: EUS-CILA was technically successful in all five cases. No major complications occurred during the follow-up period. Body weight of porcine did not change during the study period without any significant change in feed intake. Animals remained in excellent condition throughout the experimental period, and laboratory tests and computed tomography (CT) scans provided no evidence of a major complication. Histopathological evaluation showed complete ablation in the ablated area with clear delineation of surrounding normal pancreatic tissue. Mean ablated volume was 55.5 mm2 × 29.0 mm and mean ablated areas in the pancreatic sections of the five pigs were not significantly different (p = 0.368). CONCLUSIONS: In conclusion, our experimental study suggests that EUS-CILA is safe and has the potential to be an effective local treatment modality. No major morbidity or mortality occurred during the study period. Further evaluations are warranted before clinical application.

Stimulatory effects of wavelength-dependent photobiomodulation on proliferation and angiogenesis of colorectal cancer.

In recent decades, the laser treatment of cancer has been introduced as a promising treatment option. Because of the maldistribution of optical energy and an ambiguous boundary between the normal and tumor tissues, laser irradiation can stimulate residual cancer cells, leading to a cancer regrowth. As photobiomodulation (PBM) is involved in an extensive range of cellular responses, profound comprehension of photo-stimulated mechanisms against the cancer cells is required to establish a safety margin for PBM. Therefore, we aimed to identify the stimulant effects of PBM at various wavelengths against the tumor cells to establish a safety margin for the laser treatment. CT26 murine colon cancer cells were exposed to either 405 (BL), 635 (VIS), or 808 (NIR) nm laser lights at the fluences of 0, 10, 30, and 50 J/cm2. In addition, CT26 tumor-bearing mice were irradiated with BL, VIS, or NIR at a fluence of 30 J/cm2. Both the proliferation and angiogenesis potential of the CT26 cells and tumors were evaluated using the MTT assay, western blot, and immunohistochemistry (IHC) staining analyses. Although cell viability was not statistically significant, BL significantly induced p-ERK upregulation in the CT26 cells, indicating that PBM with BL can stimulate proliferation. In vivo tests showed that the NIR group exhibited the maximum relative tumor volume, and BL yielded a slight increase compared to the control. In the IHC staining and western blot analyses, both BL and NIR increased the expression of EGFR, VEGF, MMP-9, and HIF-1α, which are related to the proliferation and angiogenesis-related factors. Further investigations will be pursued to clarify the molecular pathways that depend on the cancer cell types and laser wavelengths for the establishment of safety guidelines in clinical environments.

Endoscopic Ultrasound-Guided Laser Ablation Using a Diffusing Applicator for Locally Advanced Pancreatic Cancer Treatment.

Endoscopic ultrasound (EUS)-guided cylindrical interstitial laser ablation (CILA) procedures can be used to treat unresectable pancreatic cancer (PC). The aim of this study was to investigate the acute responses of pancreatic tissue after EUS-guided CILA in vivo in porcine models. Eight pigs were tested to compare the effects of different energy levels on pancreatic tissue ablation. A 1064 nm laser system was used to deliver 5 W through a diffusing applicator. The EUS-guided CILA was performed under four different energies: 200, 400, 600, and 800 J. Three days after the experiments, histological analysis was performed. The CILA consistently generated circular coagulated necrosis (CN) in the cross-sectioned pancreatic tissue. The ablation diameter was linearly dependent on the total energy delivery. The area of the CN initially increased with total energy delivery but became saturated at 600 J. The width of the degenerative parenchyma (DP) in the native tissue beyond the CN region increased with the total energy up to 600 J, and then decreased afterward. EUS-guided CILA can be a feasible approach for treating PC. Further animal studies will investigate the chronic responses of the pancreatic tissue to examine the efficacy and safety of the proposed method for clinical translation.

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.