available at www.jstage.jst.go.

jp/browse/islsm

ORIGINAL ARTICLES

Ex vivo efficacy evaluation of laser vaporization

for treatment of benign prostatic hyperplasia
using a 300-W high-power laser diode
with a wavelength of 980 nm
Junya Takada 1, Norihiro Honda 2, Hisanao Hazama 1, Kunio Awazu 1,3,4

1: Graduate School of Engineering, Osaka University

2: Institute for Academic Initiatives, Osaka University
3: Graduate School of Frontier Biosciences, Osaka University
4: The Center for Advanced Medical Engineering and Informatics, Osaka University

Background and Objective: Laser vaporization of the prostate is considered to be a promising

treatment for benign prostatic hyperplasia (BPH), and efficiency of vaporization and hemostasis are
both important parameters for such treatment. In this study, we used a high-power laser diode
with a wavelength of 980 nm to obtain high vaporization efficiency with good hemostasis. The
objective of this study is to evaluate the efficacy of laser vaporization for treatment of BPH in ex
vivo experiments using a 300-W high-power laser diode with a wavelength of 980 nm quantitatively.
Materials and Methods: An ex vivo experimental setup simulating clinical treatment situation was
constructed. Bovine prostate tissue was used as a sample. The power setting was 100, 150, 200,
250, or 300 W, and the irradiation time was 0.5, 1, or 2 s. After laser irradiation, vaporized and
coagulated depths were measured.
Results: The vaporized depth increased with the laser power and irradiation time, and the results
confirmed that the high-power laser diode could efficiently vaporize the prostate tissue.
Coagulated depth increased as the laser power became higher.
Conclusions: Laser vaporization of prostate tissue using a high-power laser diode with a wavelength of 980 nm represents a promising treatment for BPH; this method exhibits high vaporization
efficiency and good hemostasis. However, operators must be aware of the risk of postoperative
perforation of the prostatic capsule caused by coagulation of deep regions that cannot be visualized by endoscopic observation.
Key words: absorption coefficient laser surgery scattering coefficient transurethral vaporization
of the prostate

Introduction
The lasers, such as the holmium:yttrium aluminum garnet (Ho:YAG) laser at a wavelength of 2140 nm and
the frequency-doubled Nd:YAG (potassium titanyl
phosphate [KTP]) laser at a wavelength of 532 nm have
been used most commonly for benign prostatic hyperplasia (BPH) instead of transurethral resection of the
Addressee for Correspondence:
Kunio Awazu, Ph.D., Dr.Med.Sci.
Adderess: Bldg.A1, 2-1 Yamadaoka, Suita,
Osaka, 565-0871, Japan
TEL: +81-6-6879-7885, FAX: +81-6-6879-7363
E-mail: awazu@see.eng.osaka-u.ac.jp
2014 JMLL, Tokyo, Japan

prostate (TURP), which is likely to cause bleeding and

transurethral resection sydrome. 1-5) Although the
Ho:YAG laser is superior in terms of the cutting capability due to the high absorption coefficient of water
and holmium laser enucleation of the prostate (HoLEP)
is a useful treatment, HoLEP requires the operator to
be highly skilled. 6,7) By contrast, the KTP laser is
delivered transparently through water but is strongly
absorbed by hemoglobin. Thus, laser vaporization of
the prostate by KTP laser can be performed with good
hemostasis, but it requires a long operating duration.
Received Date: February 10th 2014
Accepted Date: July 18th 2014

Laser Therapy 23.3: 165-172

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ORIGINAL ARTICLES
3,4,8,9)

In recent years, a 980-nm laser diode has been

applied to laser vaporization of the prostate. 5,9,10) This
wavelength offers high simultaneous absorption by
water and hemoglobin, so it combines efficient vaporization of the prostate with good hemostasis. 9,10) In
addition, the resultant increase in vaporization efficiency shortens the duration of the operation.
Although the coagulation induced around the
vaporized area is useful for hemostasis, the areas damaged by coagulation and necrosis cause irritative
events and perforation postoperatively. 11,12) Therefore,
it is necessary to quantitatively evaluate not only the
vaporization depth but also the depths of coagulation
and necrosis.
A high-power laser diode at a wavelength of 980
nm and a output power of 300 W has the potential to
treat BPH safely and effectively. However, the interactions between laser light and prostate tissue have never
been quantitatively measured. Therefore, in this study,
we constructed an ex vivo experimental setup simulating a clinical treatment situation, and quantitatively
evaluated the safety and efficacy of laser vaporization
of the prostate using a high-power laser diode at a
wavelength of 980 nm.

Materials and Methods

available at www.jstage.jst.go.jp/browse/islsm

slides after slicing to a thickness of about 1 mm.

The optical properties were measured using a
double-integrating-sphere optical system and the
inverse Monte Carlo method. 13,14) The double-integrating-sphere optical system was used to measure the diffuse reflectance Rd and the total transmittance Tt of the
tissues, taking optical scattering into account. The sample was placed between two integrating spheres
(CSTM-3P-GPS-033SL, Labsphere, Inc., USA) and irradiated with white light from a xenon lamp (L2274[GS],
Hamamatsu Photonics K.K., Japan). The first sphere
was used to collect the diffusely reflected light, whereas
the second sphere was used to collect the transmitted
light. The light from each integrating sphere was transmitted through an optical fiber (CUSTOM-PATCH2243142, Ocean Optics, Inc., USA) to a spectrometer
(Maya2000-Pro, Ocean Optics), and measured with an
exposure time of 100 ms. From the measured values Rd
and Tt, the set of optical properties of the tissue, i.e.,
the absorption coefficient a and scattering coefficient
s, were calculated using the inverse Monte Carlo
method. 13,14) We used Monte Carlo calculation code
obtained from the website of the Oregon Medical Laser
Center at Providence St. Vincent Medical Center. 15) The
reduced scattering coefficient s' was calculated by
s' = (1g)s,

Measurement of optical properties

Because it is difficult to obtain a regular source of
human prostate tissue, we used bovine prostate tissue
to evaluate the effects of laser irradiation. To validate
this model, we first measured the optical properties of
bovine prostate. The human prostate tissue was
extracted from a patient for treatment of BPH by TURP.
Then, the prostate tissue was kept in saline at 4C for
16 days. The bovine prostate tissues were obtained
from cattle originally slaughtered to obtain meat. The
prostate tissues were immediately delivered in cold
storage and were subsequently kept in saline at 4C for
2 days. It should be noted that the human prostate tissue was not extracted for this study and we also
obtained the patients consent about the aim of this
study. Similarly, the cattle was not sacrificed for this
study. The prostate tissues were sliced to a thickness of
about 1 mm, and placed in a sample holder made from
two glass slides and spacers with a thickness of 1 mm.
Fig. 1 shows a schematic of a sliced tissue placed in a
sample holder and photographs of human and bovine
prostate tissues used for the measurement of optical
properties. The photographs of (b) and (c) are a part
of a sample placed in a sample holder from two glass

166

Fig. 1: (a) Schematic of a sliced tissue placed in a sample holder and photographs of (b) human (c)
bovine prostate-tissue samples used for the
measurement of optical properties.

Takada J et al

ORIGINAL ARTICLES

available at www.jstage.jst.go.jp/browse/islsm

where g is the anisotropy factor of scattering, here set

to 0.862. 16) Optical penetration depth was calculated
by

1
3 a ( a + s ' )

where is the depth at which the power density

decreases to 1/e of its initial value at the surface. 17)

Ex vivo experimental setup for laser irradiation

Laser irradiation was performed using a 300-W highpower laser diode at a wavelength of 980 nm (Ceralas
HPD 300, Biolitec AG, Germany) and an optical fiber
with a curved tip (Twister TM Large Fiber, Biolitec).
18,19) The core diameter and the length of the optical
fiber were 600 m and 3 m 19), respectively. Fig. 2
shows a photograph of the laser light emitted from the
optical fiber and scattered in an aqueous suspension of
lipid droplets. Laser light was emitted in a direction
about 21 from the axis of the optical fiber. The output
laser power emitted from the tip of the fiber was calibrated using a power meter (FL400A-BB-50, Ophir
Optronics Solutions Ltd., Israel).
Fig. 3 shows the ex vivo experimental setup.
The clinical treatment of BPH is performed using a
rigid endoscope under circulating saline, and laser
irradiation is performed by placing the tip of the
optical fiber in contact with the surface of the
prostate. Similarly, in this ex vivo experimental setup,
laser irradiation was performed in saline by placing
the tip of the optical fiber in contact with the surface
of the prostate sample, and a stainless-steel tube was

used to simulate the working channel of the rigid

endoscope. An optical fiber with a maximum diameter of 1.85 mm was inserted through a stainless-steel
tube. The inner diameter and length of this stainlesssteel tube were 3.19 and 115 mm, respectively. The
plastic case was filled with saline, and the stainlesssteel tube and the joint were covered with a heatshrinkable tube to prevent leakage of saline. A segment of bovine prostate tissue was put on a cork
board and immersed in saline. The height of the surface of the prostate tissue was adjusted by placing
rubber boards under the cork board. In order to minimize the variation from sample to sample, all samples of bovine prostate tissue were delivered and
kept in the same way as those used for measurement
of the optical properties. The size of the sample was
about 4060 mm 2 . The laser irradiation was performed in continuous-wave mode; the power setting
was 100, 150, 200, 250, or 300 W, and the irradiation
time was 0.5, 1, or 2 s. In this study, the fiber tip was
in contact with the surface of the prostate tissues
during laser irradiation. Therefore, the spot size for
laser irradiation was almost same as the core diameter of 600 m.
In the clinical treatment of BPH by the laser system and optical fiber used in this study, the tip of the
optical fiber must in contact with the surface of the

Heat-shrinkable tube
Stainless steel tube
Saline

Optical fiber

Weights

Bovine prostate
Cork board
Rubber board

(a)

Tip of the optical fiber

Heat-shrinkable tube

Stainless-steel tube
Rubber board
Cork board

Optical fiber

Bovine prostate

21
Saline

Weights

(b)
Fig. 2: Photograph of laser light emitted from the optical fiber and scattered in an aqueous suspension of lipid droplets.

BPH treatment using a 300-W 980-nm Laser

Fig. 3: (a) Schematic and (b) photograph of the ex vivo

experimental setup for contact laser irradiation.

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respectively. Table 1 shows the measured optical

properties of human and bovine prostate tissues at a
wavelength of 980 nm. The absorption coefficient a
and the reduced scattering coefficient s' of human
prostate tissue were similar to those of the bovine
prostate tissue. Thus, the optical penetration depth of
the human prostate tissue was also similar to that of
the bovine prostate tissue. These results suggest that
bovine prostate tissue is a valid model for human
prostate tissue for evaluation of the effects of laser irradiation.
The sliced tissues might be different from the living tissue in the amount of blood. Since all samples
were stored in saline, blood might flow away from the
samples. As shown in Fig. 4, the difference in the
height of absorption peaks of the human and bovine
prostate tissues at the wavelength of about 420 and
550 nm are caused by the difference in the amount of
blood. However, the effect of the difference in the
amount of blood is negligible at the wavelength of 980
nm as shown in Fig. 4.

prostate tissue and must continuously be moved by

manual operation of the doctor. Therefore, it is expected that the irradiation time for a point on the prostate
tissue is less than 1 s. Thus, the irradiation times of 0.5
and 1 s were set as the normal irradiation time, and the
irradiation time of 2 s was set under the assumption of
excessive irradiation condition.
After laser irradiation, the prostate tissue was cut
at the center of the irradiation point, vertically to the
surface, and the cross-section was observed to measure
the vaporized and coagulated depths. The irradiated
prostate tissues were fixed with a histological fixative
(Mildform 20NM, Wako Pure Chemical Industries,
Ltd., Japan) and stained with hematoxylin and eosin.
Histological analysis was performed by Histo Science
Laboratory Co., Ltd. (Japan).

Results and Discussion

Optical properties of human and bovine prostate
tissues

Vaporized and coagulated depths

Fig. 5 shows a typical photograph of the surface and a

Reduced scattering coefficient

[mm-1]

Absorption coefficient
[mm-1]

Fig. 4 shows the measured absorption and scattering

spectra of both human and bovine prostate tissues,

1
- - Human rostate tissue

0.8

Bovine prostate tissue

0.6
0.4
0.2
0
400

500

600

700

800

900 1000

Wavelength [nm]

5
- - Human rostate tissue

Bovine prostate tissue

3
2
1
0
400

500

600

700

800

900 1000

Wavelength [nm]

(a)

(b)

Fig. 4: The measured (a) absorption and (b) reduced scattering coefficient spectra
of the human and bovine prostate tissues in at the wavelength of 3501000
nm.
Table 1: Absorption coefficient a, reduced scattering coefficient s', and optical penetration depth of the
prostate tissues at a wavelength of 980 nm, measured using a double-integrating-sphere optical system and the inverse Monte Carlo method. n indicates the number of samples.
a [mm1]

s' [mm1]

[mm]

Human prostate tissue (n = 1)

0.066

0.81

2.4

Bovine prostate tissue (n = 3)

0.061 0.021

0.61 0.04

2.9 0.5

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typical histological image of bovine prostate tissue after

laser irradiation. The histological image reveals that the
surface of the vaporized region was slightly carbonized
and surrounded by a coagulated region, although the
extent of carbonization was negligible.
Fig. 6 shows the relationship between the vaporized depth and the power setting for each irradiation
time. The vaporized depth increased with laser power

ORIGINAL ARTICLES
and irradiation time. Statistical comparison was made
using the t-test, and differences were considered to be
significant at p < 0.05. Significant differences were
observed between power setting of 100 and 300 W for
the irradiation time of 0.5 and 1 s. Therefore, the 300W high-power laser diode at 980 nm can efficiently
vaporize the prostate tissue for the short irradiation
time and contribute to a reduction in the duration of

Vaporized region

Vaporized region

1 mm

5 mm
Coagulated region

Coagulated region

(a)

(b)

Fig. 5: (a) Typical photograph of the surface and (b) typical histological image of bovine prostate
tissue following laser irradiation with a laser power setting of 200 W and an irradiation
time of 1 s. The histological sample was stained with hematoxylin and eosin.

6
5
4
3

Setting power
100 W
150 W
200 W
250 W
300 W

p < 0.05 n = 5

Coagulated depth [mm]

Vaporized depth [mm]

2
1
0

6
5
4
3
2

p < 0.05 n = 5

Setting power
100 W
150 W
200 W
250 W
300 W

1
0

0.5

Irradiation time [s]

Fig. 6: Relationship between the vaporized depth and
the laser power setting for each irradiation time.
n indicates the number of the samples. Data are
expressed as means, and the error bars are the
standard deviations of the mean.
BPH treatment using a 300-W 980-nm Laser

0.5

1
Irradiation time [s]

Fig. 7: Relationship between the coagulated depth and

the laser power setting for each irradiation time.
n indicates the number of the samples. Data are
expressed as means, and the error bars are the
standard deviations of the mean.
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the operation. In the irradiation time of 2 s, the deviation of the vaporized depth among samples at all setting power was large, so no significant differences
were observed. The optical penetration depth of
bovine prostate tissue shown in table 1 was 2.9 0.5
mm at a wavelength of 980 nm. Although the samples
were prepared on the same protocol, the variation
from sample to sample might involve the deviation of
the vaporized depth in view of the deviation of the
optical penetration depth.
The photothermal effect induced by laser irradiation was used for removal of prostate tissue in this
treatment method. When laser light is irradiated to the
prostate tissue, the rapid increase in the local temperature of the prostate tissue leads to the rapid increase in
the local pressure due to the vaporization of the tissue,
and the section of the tissue is removed by microexplosion of the tissue 20).
Fig. 7 shows the relationship between the coagulated depth and the power setting for each irradiation
time. The coagulated depth also increased with laser
power and irradiation time. However, the change in
the coagulated depth was relatively smaller than the
change in the vaporized depth. Although coagulation
is useful for hemostasis, 21) excessively deep coagulation can irritate the urethra and lead to postoperative
perforation. 12) Therefore, excess coagulation should
be avoided. The results shown in Figs. 6 and 7 indicate that vaporization using the 300-W high-power
laser results in minimal coagulation as well as a high
vaporization rate. Operators can use endoscopic observation to recognize and control the extent of vaporization; however, endoscopy cannot reveal the extent of
coagulation during the operation. To prevent postoperative perforation, operators need to understand the
relationship between the coagulated depth and the
laser-irradiation conditions, and be aware of the risk of
postoperative perforation of the prostatic capsule.
Irradiation effects by a laser diode with the wavelength of 980 nm have been investigated in previous
preclinical and clinical studies. A preclinical study
using a 150-W laser diode with 980 nm showed that
deep coagulation caused by laser irradiation led to prostatic slough-induced obstruction and perforation in six
of eight surviving animals. 22) On the other hand, a
previous clinical study suggested that the clinical outcomes by a 300-W laser diode with 980 nm were good.
Considering the results of these studies, the laser-tissue
interaction should be evaluated quantitatively irrespective of operators skill. Therefore, ex vivo evaluation

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using a 300-W laser diode with 980 nm was conducted

in this study.
In a previous ex vivo experiment using porcine
kidneys at a laser power of 80 W, the vaporization rate
at 980 nm was higher than the rate at 532 nm using a
KTP laser, whereas the hemostatic properties of the
two wavelengths were equivalent. 9) The results of this
study showed that the coagulated depth increased with
laser power and irradiation time. Considering coagulation is useful for preventing bleeding, the 300-W highpower laser diode at a wavelength of 980 nm contributes to the treatment with good hemostasis. 9)
Therefore, the 300-W high-power laser diode at a
wavelength of 980 nm should be useful for treatment
of BPH with high vaporization rate and good hemostasis. However, this study did not evaluate the hemostatic properties directly, so additional in vivo study or ex
vivo study are needed for precise evaluation of the
hemostatic properties.
This study evaluated the efficacy of laser vaporization using the 300-W high-power laser diode. As a
similar study, a study using a high-power laser diode at
a wavelength of 980 nm has already been performed.
24) This previous study conducted an ex vivo experiment using a 200-W high-power laser diode with 980
nm and showed that the vaporized volume increased
with laser power. Although this previous study suggested a relationship between power setting and
vaporization similar to this study, it is different from
this study in the irradiation method between this study
and the previous study, such as the shape of the optical fibers and the contact laser irradiation. The optical
fiber used in this study has a unique shape and laser
light is emitted in a direction about 21 from the axis
of the optical fiber. It is designed for laser irradiation in
a contact mode, so it is easy to contact the prostate tissue and can achieve laser irradiation with high energy
density relative to the side firing fiber. 18) The high
power density at the tip causes instant tissue vaporization with a minimal coagulative layer beneath the
ablated surface. 18)

Conclusion
In this study, we quantitatively evaluated the effects of
laser vaporization of the prostate using a 300-W highpower laser diode at a wavelength of 980 nm, in an ex
vivo experiment simulating the clinical situation. The
results of the ex vivo experiments showed that vaporized and coagulated depths increased with laser power

Takada J et al

available at www.jstage.jst.go.jp/browse/islsm

setting and irradiation time. However, the change in

the coagulated depth was relatively smaller than the
change in the vaporized depth. These results suggest
that laser vaporization of the prostate using a 300-W

ORIGINAL ARTICLES
high-power laser diode at a wavelength of 980 nm represents a potentially effective treatment for BPH with
high vaporization rate and good hemostasis.

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[Acknowledgements]
The authors thank Reiko Ikahata, Hiromi Sekizaki, and Takashi Kuroda of Integral Corp. for their technical support.

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