Enhanced photothermal hemostasis using dual wavelengths in an in vivo leporine kidney model.

The current study investigated the hemostatic effect of dual wavelengths on in vivo leporine kidney tissue using 532-nm and 980-nm laser systems. Three irradiation modes, 532 nm, 980 nm, and dual (532 and 980 nm) modes, were compared to test non-contact photothermal hemostasis on 36 bleeders in the kidney models. Each bleeder was flushed with saline during the irradiation. The dual mode achieved complete hemostasis more rapidly than the single modes (4.0 ± 1.4 s for dual vs. no hemostasis for 532 nm and 10.0 ± 1.3 s for 980 nm; p < 0.001). Application of 60 W from the dual wavelengths expanded the surface area of the thermal lesion (up to 60%). In vivo dual-wavelength irradiation achieved more rapid and complete hemostasis with ∼2 mm coagulation depth than the single-wavelength irradiation.

Numerical Response Surfaces of Volume of Ablation and Retropulsion Amplitude by Settings of Ho:YAG Laser Lithotripter.

Objectives: Although laser lithotripsy is now the preferred treatment option for urolithiasis due to shorter operation time and a better stone-free rate, the optimal laser settings for URS (ureteroscopic lithotripsy) for less operation time remain unclear. The aim of this study was to look for quantitative responses of calculus ablation and retropulsion by performing operator-independent experiments to determine the best fit versus the pulse energy, pulse width, and the number of pulses. Methods: A lab-built Ho:YAG laser was used as the laser pulse source, with a pulse energy from 0.2 J up to 3.0 J and a pulse width of 150 µs up to 1000 µs. The retropulsion was monitored using a high-speed camera, and the laser-induced craters were evaluated with a 3-D digital microscope. The best fit to the experimental data is done by a design of experiment software. Results: The numerical formulas for the response surfaces of ablation speed and retropulsion amplitude are generated. Conclusions: The longer the pulse, the less the ablation or retropulsion, while the longer pulse makes the ablation decrease faster than the retropulsion. The best quadratic fit of the response surface for the volume of ablation varied nonlinearly with pulse duration and pulse number.

Dual-wavelength-assisted thermal hemostasis for treatment of benign prostate hyperplasia.

Laser treatment on a large size of prostate gland often encounters significant bleeding that can prolong the entire procedure and cause urinary complications. The current study investigates the feasibility of dual-wavelength (532 and 980 nm) application to achieve rapid hemostasis for 532-nm laser prostatectomy. Porcine kidney and bleeding phantom models were tested to quantify the degree of the irreversible tissue coagulation and to estimate the time for the complete hemostasis, respectively. The ex vivo kidney testing verifies that the dual-wavelength created up to 40% deeper and 25% wider coagulation regions than a single wavelength does. The bleeding phantom testing demonstrates that due to the enhanced thermal effects, the simultaneous irradiation yields the complete photocoagulation (~11 seconds) whereas 532 or 980 nm hardly stops bleeders. Numerical simulations validate that the combined optical-thermal characteristics of both the wavelengths account for the augmented thermal coagulation. The dual-wavelength-assisted coagulation can be a feasible treatment to entail the rapid hemostasis and to facilitate the laser prostatectomy in an effective manner.

Calculus migration characterization during Ho:YAG laser lithotripsy by high-speed camera using suspended pendulum method.

Calculus migration is a common problem during ureteroscopic laser lithotripsy procedure to treat urolithiasis. A conventional experimental method to characterize calculus migration utilized a hosting container (e.g., a "V" grove or a test tube). These methods, however, demonstrated large variation and poor detectability, possibly attributed to the friction between the calculus and the container on which the calculus was situated. In this study, calculus migration was investigated using a pendulum model suspended underwater to eliminate the aforementioned friction. A high-speed camera was used to study the movement of the calculus which covered zero order (displacement), first order (speed), and second order (acceleration). A commercialized, pulsed Ho:YAG laser at 2.1 µm, a 365-µm core diameter fiber, and a calculus phantom (Plaster of Paris, 10 × 10 × 10 mm3) was utilized to mimic laser lithotripsy procedure. The phantom was hung on a stainless steel bar and irradiated by the laser at 0.5, 1.0, and 1.5 J energy per pulse at 10 Hz for 1 s (i.e., 5, 10, and 15 W). Movement of the phantom was recorded by a high-speed camera with a frame rate of 10,000 FPS. The video data files are analyzed by MATLAB program by processing each image frame and obtaining position data of the calculus. With a sample size of 10, the maximum displacement was 1.25 ± 0.10, 3.01 ± 0.52, and 4.37 ± 0.58 mm for 0.5, 1, and 1.5 J energy per pulse, respectively. Using the same laser power, the conventional method showed <0.5 mm total displacement. When reducing the phantom size to 5 × 5 × 5 mm3 (one eighth in volume), the displacement was very inconsistent. The results suggested that using the pendulum model to eliminate the friction improved sensitivity and repeatability of the experiment. A detailed investigation on calculus movement and other causes of experimental variation will be conducted as a future study.

Effects of In Utero Exposure to Ethinyl Estradiol on Tamoxifen Resistance and Breast Cancer Recurrence in a Preclinical Model.

Background: Responses to endocrine therapies vary among patients with estrogen receptor (ER+) breast cancer. We studied whether in utero exposure to endocrine-disrupting compounds might explain these variations. Methods: We describe a novel ER+ breast cancer model to study de novo and acquired tamoxifen (TAM) resistance. Pregnant Sprague Dawley rats were exposed to 0 or 0.1 ppm ethinyl estradiol (EE2), and the response of 9,12-dimethylbenz[a]anthracene (DMBA)-induced mammary tumors to 15 mg/kg TAM, with (n = 17 tumors in the controls and n = 20 tumors in EE2 offspring) or without 1.2 g/kg valproic acid and 5 mg/kg hydralazine (n = 24 tumors in the controls and n = 32 tumors in EE2 offspring) in the female offspring, was assessed. One-sided Chi2 tests were used to calculate P values. Comparisons of differentially expressed genes between mammary tumors in in utero EE2-exposed and control rats, and between anti-estrogen-resistant LCC9 and -sensitive LCC1 human breast cancer cells, were also performed. Results: In our preclinical model, 54.2% of mammary tumors in the control rats exhibited a complete response to TAM, of which 23.1% acquired resistance with continued anti-estrogen treatment and recurred. Mammary tumors in the EE2 offspring were statistically significantly less likely to respond to TAM (P = .047) and recur (P = .007). In the EE2 offspring, but not in controls, adding valproic acid and hydralazine to TAM prevented recurrence (P < .001). Three downregulated and hypermethylated genes (KLF4, LGALS3, MICB) and one upregulated gene (ETV4) were identified in EE2 tumors and LCC9 breast cancer cells, and valproic acid and hydralazine normalized the altered expression of all four genes. Conclusions: Resistance to TAM may be preprogrammed by in utero exposure to high estrogen levels and mediated through reversible epigenetic alterations in genes associated with epithelial-mesenchymal transition and tumor immune responses.

Water content contribution in calculus phantom ablation during Q-switched Tm:YAG laser lithotripsy.

Q-switched (QS) Tm:YAG laser ablation mechanisms on urinary calculi are still unclear to researchers. Here, dependence of water content in calculus phantom on calculus ablation performance was investigated. White gypsum cement was used as a calculus phantom model. The calculus phantoms were ablated by a total 3-J laser pulse exposure (20 mJ, 100 Hz, 1.5 s) and contact mode with N=15 sample size. Ablation volume was obtained on average 0.079, 0.122, and 0.391 mm3 in dry calculus in air, wet calculus in air, and wet calculus in-water groups, respectively. There were three proposed ablation mechanisms that could explain the effect of water content in calculus phantom on calculus ablation performance, including shock wave due to laser pulse injection and bubble collapse, spallation, and microexplosion. Increased absorption coefficient of wet calculus can cause stronger spallation process compared with that caused by dry calculus; as a result, higher calculus ablation was observed in both wet calculus in air and wet calculus in water. The test result also indicates that the shock waves generated by short laser pulse under the in-water condition have great impact on the ablation volume by Tm:YAG QS laser.