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Lasers in Medicine Rodney Perkins, M.D. In nature, periodic mutation creates new life-forms and moves the species to new levels of performance and being. Similarly, from time to time in human endeavors, mutative cerebration provides important new concepts that we can then refine and develop into processes that we hope will enrich the human , . . condition. The laser is such a type of contribution. Its impact is already widespread in science, communication, industry, and medicine. This impact will grow rapidly as we better understand its nature, develop permutations, and integrate both basic and advanced forms closely with other core technologies to produce hybrids that can satisfy as yet unknown needs. The use of the laser in medicine and surgery has a relatively short pedigree of less than two decades. Although the range of laser radiation extends both below and above the visible portion of the electromagnetic spectrum, that radiation is, in a sense, only a special form of light. The use of other forms of light in medicine has a longer history. There is documentation that the ancient Egyptians recognized and used the therapeutic power of light as long as 6,000 years ago (Figure 1~. Patches of depigmen- ted skin, now referred- to as vitiligo, were cosmetically undesir- able. Egyptian healers reportedly crushed a plant similar to presentday parsley and rubbed the affected areas with the crushed leaves. Exposure to the sun's radiation produced a severe form of sunburn only in the treated areas. The erythema LIGHT IN MEDICINE 101

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~ 02 RODNEY PERKINS, M.D. 1 1 FIGURE 1 The ancient Egyptians recognized many beneficial qualities of solar radiation. Photograph by Glenn Calderhead. subsided, leaving hyperpigmentation in the previously depig- mented areas. In Europe in the late eighteenth and early nineteenth centu- ries, at the height of the Industrial Revolution, a myriad of factories and industrial plants spewed smoke into the atmo- sphere, filtering out many of the beneficial components of the sun's rays. Deprivation of ultraviolet radiation contributed to calcium deficiency in the main skeletal bones, leading to the characteristic deformity known as rickets. The much more insidious and fatal pulmonary tuberculosis was also prevalent. It was found that sunlight helped alleviate the symptoms of these diseases, and so sanitariums sprang up all over Europe, espe- cially in Great Britain and Switzerland. They were usually located on higher ground or by the sea, because this seemed to increase the efficacy of the therapy. We now know that pure air filters out fewer of the beneficial components of solar radia- t~on. In the late nineteenth century, the Danish scientist Nils Finsen used a quartz-and-water cooling system to extract the ultraviolet from both solar and man-made arc-lamp radiation to treat various skin conditions, such as vitiligo and psoriasis, a scaly overproduction in areas of skin. The significance of Finsen's

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LASERS IN MEDICINE 103 work was that, for the first time, an artificial light source was being used therapeutically. Sixty years later, only a quarter of a century ago, a light source more powerful than the sun was developed by Theodore H. Maiman at the Hughes Research Laboratories in Malibu, Cali- fornia, heralding a new era in phototherapy. Maiman's laser used a ruby crystal to produce its intense deep red beam. Other lasers using different media soon emerged. In 1960, Ali tavan created the helium-neon gas laser, first emitting in the infrared part of the spectrum and a year later in the important red line. A year later Peter A. Franken demonstrated that certain crys- talline materials could effectively double the frequency of an incident beam. The year 1964 was a prolific year for laser development and yielded an outstanding harvest of lasers used in clinical medicine. C. Kumar N. Patel introduced the carbon dioxide (CO2) gas laser, which produced an invisible beam in the far infrared. Another invisible laser in the near infrared, the neodymium yttrium-aluminum garnet (Nd:YAG) was contrib- uted by Guesic, Marcos, and Van Uitert. The argon gas laser emitting in the visible blue-green spectrum was demonstrated by William Bridges. Since then, literally thousands of substances have been used to produce laser energy. However, those first few that appeared so close together, in general, have remained until today the most popularly used lasers in clinical medicine and surgery (Plate 41. Maiman's ruby laser, although still occasionally used in some dermatological applications, is no longer in common medical use. The helium- neon laser is mainly used as an aiming beam for the invisible infrared CO2 and Nd:YAG lasers. The argon laser is used extensively in ophthalmology and dermatology and less so in orology, neurosurgery, urology, and gynecology. Both infrared lasers, the Nd:YAG and particularly the CO2, have found a variety of clinical applications. The CO2 laser has been used to vaporize tissue in almost every specialty, whereas the Nd:YAG laser has been used primarily for tissue coagulation in gastroen- terology and urology. A specialized short-pulse, high peak power Nd:YAG laser has been used effectively in ophthalmol- ogy after cataract surgery. Frequency-doubled lasers were used only experimentally until a higher power laser was made possible by using doubling crystals of potassium titanyl phosphate (KTP) developed by J. Bierlein at Du Font. The laser that resulted from doubling the Nd:YAG with KTPcalled the KTP/532 laser began clinical use in 1983 and is now being applied in a wide variety of surgical . . specla. ales.

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~ 04 RODN BY PERK NS, M. D. MINIMALLY INVASIVE SURGERY 11 Why is the laser used in medicine, and why is its use increasing? Some answers can be found by looking at a few of the universal changes occurring in medicine. Economic, political, and socio- logical factors in our society frequently affect the disposition of scientific discovery, just as scientific and technological progress influences broad changes in the nontechnical spheres of human activity. These factors are Newtonian in the sense that actions in one sphere of activity have a direct influence on actions in other spheres. In the past decade, there has been a growing trend toward a less invasive style of surgical intervention. This style is charac- terized by achieving a maximal treatment effect with minimal damage to surrounding and overlying normal structures and is termed minimally invasive surgery, or MIS. The trend toward MIS is being driven by a multiplicity of factors. High-technology diagnostic devices, such as computer- ized axial tomography, magnetic resonance imaging, as well as sophisticated optical devices in the form of flexible fiber-optic endoscopes and intravascular catheters, have enhanced our ability to identify disease processes early and locate them accu- rately. Generally, the earlier a tumor or growth can be identi- fied, the more responsive it is to therapy by a minimally invasive technique. Human psychology is also part of this changing equation. Everyone has an inborn fear of standard invasive surgical procedures. Given an equivalent surgical outcome, we will almost always choose a less invasive procedure. The increase in patient consumerism, coupled with rapid and widespread trans- mission of information on new MIS procedures through video and popular print media, also fuels this trend. Economics exerts a strong influence on the trend toward MIS. These procedures are cost-effective to insurers, corporations, and the government, since most are done on an outpatient basis. This results in reduced cost, lower morbidity, and less time away from work. Even when MIS techniques are used as an adjunct to more invasive surgical approaches, reduced destruction of tissue frequently leads to quicker recovery with a shortened, lower cost hospitalization. The laser is an integral part of this trend toward MIS. It is well suited to MIS because it can create precision surgical effects at a distance. Laser energy can be transmitted through endoscopic devices passed through the body's natural orifices, or it-can be

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LASERS IN MEDICINE ]05 delivered through transdermal probes that require minimal incisions of 1 cm or less. This is particularly true for those wave- lengths transmissible through quartz fiber-optic waveguides. Controlled tissue effects can also be delivered noninvasively. This is commonly done in the treatment of intraocular condi- tions and intradermal lesions by wavelengths characterized by high transmissiveness through the ocular and dermal media. The laser is a very effective tool for the surgeon who under- stands its advantages and limitations. The surgeon's knowledge of laser science need not be as detailed as that of the physicist but should include a general understanding of principles of light transmission, reflection, scatter, and absorption. An under- standing of the interaction of the various wavelengths in tissue components with widely differing coefficients of absorption provides the primary basis for safe and effective surgical appli- cation of this new technology. The biological effect of lasers is a function of three elements: laser wavelength, energy density, and tissue absorption (Figure 21. For the surgeon, it is helpful to look upon wavelengths as the nature or character of the surgical instrument and upon energy density as the "dosage." The coefficient of absorption of the target tissue might be thought of as a sponge for this therapeutic light, but is more difficult to characterize and simplify. Two important constituents of tissue absorption are pigment and water. In all but the most specialized of tissues there is generally a vascular supply rich in hemoglobin pigment. Other chromophore pigments, such as melanin in skin and myoglobin in muscle, are prevalent. All tissues contain water. Visible light from argon and KTP/532 lasers is well absorbed in hemoglobin, whereas infrared radiation from Nd:YAG lasers is poorly ab- sorbed. In water, CO2 laser radiation is almost totally absorbed, whereas the visible wavelengths and Nd:YAG laser radiation have little absorption. Thus, each of the surgical laser wave- lengths has advantages and disadvantages depending upon the target tissue and the surgical effect desired. It is not completely accurate to generalize about the relative amounts of penetration and scatter of these surgical lasers in tissue, because that is a function of wavelength and the specific absorption characteristics of individual tissues. However, if we consider a hypothetical nominal soft tissue with a mixture of tissue types found in the body, we can compare the general BIOLOGICAL EFFECTS 1 1

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~ 06 RODNEY PERKINS, M.D. FIGURE 2 The biological effect of lasers is a function of three main factors. scatter of these various wavelengths. In this hypothetical model, we would find CO2 laser radiation absorbed on the surface with little forward scatter. The wavelengths of the Nd:YAG laser would have poor surface absorption and would scatter deeply into the tissue. The visible wavelengths would have forward scatter somewhat greater than the CO2 laser wavelengths but significantly less than those of the Nd:YAG laser. The thermal patterns in this conceptual model are also varied. The CO2 laser produces a surface hot spot that creates a thermal front that conducts heat into the tissue. The thermal center produced by the Nd:YAG laser is actually beneath the surface of the target tissue, thus making it difficult for the surgeon to judge the ultimate surgical effect. The visible wavelengths have some of the surface heat effect of the CO2 laser, especially once surface vaporization and some penetration into the tissue is initiated. The CO2 laser is an efficient vaporizer of tissue. The Nd:YAG laser does not characteristically vaporize tissue unless power densities are relatively high, but rather, it creates a coagulative necrosis within the tissue. The argon and KTP/532 lasers vaporize tissue effectively, especially after the process has been initiated. It is possible that as the target tissue begins to vaporize, a blanket of microscopic char particles is created on the surface and acts as a chromophore, catalyzing the surface absorption of the next quantum of visible laser light. The visible wavelength lasers are also good hemostatic coagulators. This quality proba-

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LASERS IN MEDICINE ]07 bly derives from the slight scatter, which is absorbed in the hemoglobin within the capillaries and small vessels, thus creat- ing intravascular coagulation. Carbon dioxide lasers have less hemostatic effect. This effect results primarily from the advanc- ing thermal front, not because of any specific intravascular absorption of the wavelength. Whether the laser radiation is visible or invisible, the phenomenon that causes the surgical effect is the absorption of radiant energy and its conversion into heat in the target tissue. The amount of heat generated determines the alteration of the tissue. At approximately 50C-60C, denaturation begins to occur in collagen and other proteins. At 65C and above, denaturation proceeds to extensive physical changes, including coagulation. At 80C-85C, blood vessels shrink. This effect is probably due to the alteration of the collagen within their walls and is a component of the hemostatic effect of lasers. lust below 100C small vacuoles are sometimes formed in the tissue as the slightly pressurized intra- and extracellular water begins to boil. Surface vaporization takes place at 100C, and much of the particulate matter of the tissue leaves the surface with the emitting vapor. At several hundred degrees Celsius, the remain- ing organic materials revert to their basic carboniferous form and charring occurs. An understanding of these interactions between temperature and tissue is important to the surgeon in achieving three main surgical effects: coagulating, vaporizing, and cutting. In prac- tice, the thermal boundaries between these effects are not as controllable as they are in a laboratory setting or theoretical contemplation, but the surgeon can achieve a predominant surgical effect by manipulating the one variable in the triad of the biological effect equation subject to change intraoperatively. Currently, lacking a variable-wavelength laser, the surgeon has a fixed frequency available and generally a fixed tissue coefficient of absorption as well. The only manipulable variable of the triad . ~ . Is energy density. Coagulation for hemostasis is best effected by using a lower energy density, which is achieved by enlarging the spot size or lowering the absolute power or exposure duration. The surgeon can use this technique, particularly with the visible wavelength lasers and the Nd:YAG laser, for prophylactic hemocoagulation to prevent bleeding in small vessels and vascularized target tissue and to control small vessel hemorrhage if it occurs (Figure 31. Vaporization is used to remove tissue mass primarily in tumor SURGICAL EFFECTS ll TV.

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~ 08 RODNEY PERKINS, M.D. 1 1 FIGURE 3 Coagulating to achieve hemostasis. excision. The optimum beam conditions are a large spot size and high power density to achieve a higher rate of tissue removal (Figure 4~. However, where precision is important because of vital adjacent structures, a high rate of removal may be unde- sirable for the preservation of those structures. Cutting with the laser is basically a thin linear vaporization produced by combining a high power density with as small a - 3 ~3 - -~3~3~-~-~ -4 ~-~-~33~3~ ~~-~ -A FIGURE 4 Vaporization for removal of a tissue mass.

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LASERS IN MEDICINE ]09 . . . ~. it S . ~ ~ .- . - S ^ . .~ .. T: ~ ': FIGURE 5 Cutting for incision. ........ . spot size as possible. In a way, cutting with a laser is analogous to cutting with a scalpel, which produces a high pressure density. Efficient cutting is achieved by moving the beam at a rate that produces the desired cut, yet that minimizes secondary thermal effects in the adjacent tissue (Figure 5~. The surgeon has various instruments available for cutting and must select the one most appropriate to the task and the tissue. The only advantage to cutting with the lasers now in use is the degree of hemostasis that accompanies a laser cut and the ability to cut in areas difficult to reach with conventional instruments. Although the evidence is anecdotal, some surgeons report that patients say they have less postoperative pain when tissue is excised with the laser. Safety and precision are maximized when pulses (for exam- ple, 100 ms) are used, since the damage caused by an off-target beam can be limited. The least safe use of a laser in surgery is the continuous beam, which, if it is off course, can significantly damage nontarget tissues before the surgeon can take corrective action. Between these extremes is the use of a train of pulses with a beam-free interval (for example, 100 ms on and 500 ms off). Such parameters allow the surgeon to view the effect of each pulse and aim the beam during the off interval or cancel the next pulse should problems arise. Coagulating, cutting, and vaporizing are generic surgical effects achieved throughout a procedure by manipulating the beam parameters. When combined with an understanding of 1 111

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~ ~ 0 RODNEY PERKINS, M.D. CLINICAL APPLICATIONS 1 1 the anatomy of the area and the desired therapeutic surgical alteration, the surgeon has an effective new tool that can help enhance the quality and duration of life. Surgeons of all specialties can use lasers for coagulating, vapor- izing, and cutting. However, in each medical specialty, there are certain lesions and conditions for which the laser is more commonly employed. The applications described below are not the only uses of lasers in these specialties, but they reflect the predominant current uses. OPHTHALMOlOGY Ophthalmology is the surgical specialty that is the most mature in using the laser as a therapeutic modality. In the late 1960s, pioneering ophthalmologists first applied the ruby and then the argon laser to prevent and control bleeding from retinal vessels. The visible wavelengths are well suited to this task, since they pass through the cornea, lens, and fluids of the interior of the eye with little absorption until they encounter the hemoglobin pigment within the retinal vessels or the pigment in a layer adjacent to these vessels. Here, the energy of the laser beam is absorbed, creating heat that coagulates the vessels. Control of vascular elements in the retina through laser treat- ment has preserved vision in thousands of patients with pro- liferative diabetic retinopathy and senile macular degeneration. This latter condition is the most frequent cause of blindness in people over 65 years of age. The argon laser is also used to create "spot welds" to reattach or prevent the inner neurosensory portion of the retina from separating from the outer pigmented layer in retinal tears and the early stages of retinal detachment. Glaucoma is a common condition that causes visual impair- ment. In this disorder, the normal outflow of fluids within the eye is decreased by malfunction of the filtering mechanism. The ensuing increase in pressure damages the optic nerve. The laser is used to treat these delicate filtering elements near the outer perimeter of the iris. Improvement in filtering with resultant reduction in intraocular pressure occurs in many cases, aiding in the control of this serious disorder. In some patients, a visual problem persists after removal of cataracts because of opacities in the remaining lens suspension capsule. Short, high-peak power pulses (5-10 us, about 1 mJ per

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LASERS IN MEDICINE 111 pulse) from a specialized Nd:YAG laser are beamed into the opacified membrane. The beam creates a plasma that disrupts the membrane, thus clearing the visual pathway. In experimental work now under way, lasers are being ap- plied to refractive problems of the cornea. Excimer (gas) lasers are being used to make precise cuts in various patterns outside the visual axis of the cornea. As these cuts heal, the curvature of the cornea is altered and vision is affected. Another exciting and even more experimental concept is laser corneal sculpting. Using an excimer laser combined with a computer-controlled x,y,z plane delivery system, the refractive power of the cornea is modified by changing its outer curvature. The safety and efficacy of this concept are not proved. Two potentially serious impediments are possible mutagenic effects of the ultraviolet light and clear regeneration of the protective surface epithelium of the cornea. The excimer cuts are not thermally derived, as is the case in other currently used surgical lasers. When examined histologi- cally, the edges of an excimer cut show virtually no evidence of thermal damage. This "cold cutting" is thought to be due to disruption of molecular bonds. If shown to be successful, it would have other surgical applications. DERMA TOlOGY The argon and CO2 lasers have been used for years to treat various skin conditions. More recently, the KTP/532 laser has also been shown to be effective for these disorders. The visible wavelengths work particularly well in the treat- ment of skin lesions that involve vascular abnormalities and in the removal of tattoos. The standard application is in congenital hemangiomas, which are purplish red discolorations of the skin referred to as "port wine" stains. They are basically abnormal aggregations of capillaries and small vessels in the dermis of the skin. Before the existence of the laser, little effective treatment existed for this condition. A lower power (1-2 W) argon or KTP/532 laser is beamed onto the lesion. These wavelengths pass through the relatively translucent epidermis of the skin and are absorbed in the hemoglobin inside the hemangioma network coagulating the vessel. Initially, the elimination of these vessels gives a pallorous appearance, but later, new vessels grow into the area and give it a more normal color. The artificial skin pigments that result from tattooing are removed in a similar manner. Surgeons in many specialties use the CO2 laser to vaporize and remove various raised skin lesions.

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2 RODN EY PERK! NS, M. D. OTOLARYNGOlOGY: HEAD AND NECK SURGERY The CO2 laser has been used in the treatment of laryngeal lesions since the early 1970s. Although the throat is accessible with conventional instruments, it is difficult to work deep within the throat with long instruments. Lasers are used to vaporize vocal cord polyps and other benign lesions, but they are not generally used as a primary treatment approach for obviously malignant growths. The KTP/532 laser has recently been used effectively in laryngeal lesions. Besides producing a very hemostatic vaporiza- tion, its smaller beam spot size is advantageous in making precise . . exclslona ~ cuts. Like sight, hearing also has benefited from laser technology. The argon and KTP/532 lasers are used successfully in the treatment of the hearing impairment associated with otosclerosis of the stapes. The stapes, or "stirrup," is the smallest and innermost of the three bones, or ossicles, that transmit sound vibration from the eardrum to the fluids of the inner ear (Plates 5 and 61. Otosclerosis is a benign bony growth that sometimes develops adjacent to the stapes, causing its fixation (Plate 7~. With local anesthesia, under a stereomicroscope, the eardrum is folded out of its normal position so that the laser can be beamed through the normal ear canal onto the stapes (Plates 8 and 9~. The arches of the stapes are vaporized, and the outer portion of the stapes is removed (Plates 10 and 1 11. Using 100-ms pulses of 1-2 W and a spot size of about 250 ,um, a rosette pattern of small holes is vaporized in the stapes footplate with an aggregate diameter of 0.6-0.8 mm (Plates 12 and 131. One end of a piston- shaped prosthesis is placed into the opening, contacting the inner ear fluids, and the other is attached to the adjacent ossicle, thus reestablishing the vibratory pathway (Plates 14 and 15~. This virtually vibrationless entry has several advantages over a manual technique: precision, reduced vibratory trauma to the exquisitely sensitive inner ear, and minimal morbidity, which is due to reduced vibratory stimulation of the nearby balance sensors. The procedure is routinely done on an outpatient basis, . . . wit n concomitant savings. GASTROENTEROLOGY The hemostatic effect of the Nd:YAG and argon lasers has been used to control bleeding from gastric ulcers. However, this application is being superceded by a less expensive resistance heater probe employed in a similar manner through a fiber- optic gastroscope. The Nd:YAG laser is also used to necrose . _ _

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LASERS IN MEDICINE 113 obstructive lesions of the esophagus in cancer palliation. Polyps and tumors of the colon in the lower gastrointestinal tract can also be treated with lasers. NEUROSURGERY In neurosurgery, the laser has been used primarily to vaporize solid tumors. The CO2 infrared laser has been used predomi- nantly, but visible wavelengths are used increasingly because of their superior hemostatic properties, precision, and ease of delivery. Both visible and infrared wavelengths offer increased preci- sion of removal, as well as reduced bleeding and traction on neural structures. These factors reduce patient morbidity and possibly also lower the incidence of certain potential complica- tions. Argon and CO2 lasers have been used to reduce intracta- ble pain in some paraplegics by making precise destructive lesions in the area of the spinal cord that receives the roots of . . . ~ pa~n-sens~t~ve nerve h Jers. GYNECOLOGY At present, the field of medicine that is growing most rapidly in its application of the laser is gynecology. For many years the CO2 laser has been used to vaporize areas of the uterine cervix that evidence a premalignant state. This laser procedure results in reduced bleeding and faster healing than other techniques. More recently, minimally invasive intra-abdominal surgery has been possible by combining the laser with endoscopic Instrumentation. The best example of this is the treatment of endometriosis, a condition in which tissue that normally lines the uterus is found ectopically in the lining of the interior of the pelvic abdominal cavity. At the time of monthly menses, this tissue swells and hemorrhages in a manner similar to that of the normally located endometrium of the uterus. Consequences of this condition include pain and infertility. In laser treatment for endometriosis, a 1-cm incision is made in the abdominal wall, a tube-shaped viewing laparoscope is inserted, and the patches of endometriosis are identified. A 600-,um fiber- optic waveguide lying in a channel within the laparoscope is used to deliver the vaporizing beam to the target lesions. This laser treatment of endometriosis is one of the best examples of minimally invasive surgery. Instead of requiring a standard wide abdominal incision, an effective treatment is accomplished with minimal effect on healthy tissue, virtually no blood loss, markedly reduced pain and discomfort, shorter .

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114 RODNEY PERKINS, M.D. hospitalization, earlier return to personal productivity, and lower cost. GENERAL SURGERY Laser applications in general surgery have not been developed to the same degree as in other specialties. Some general sur- geons make skin incisions with the laser, but this is rarely done. Using vaporization in combination with more traditional tech- niques when removing large tumors is probably the most com- mon use of lasers in general surgery. This limited use probably derives from the nature of the lesions that the general surgeon encounters. These lesions are usually gross tumors or conditions that require anatomical reconstruction. Also, the surgical site is usually reasonably well accessed once entry through the incision is accomplished. Such problems do not lend themselves as well to minimally invasive and precision techniques the areas in which lasers have the most advantage over standard surgical approaches. PUlMONOLOGY Obstructive mass lesions of the lower airway in the trachea and the bronchial tree are treatable with laser surgery. Through a bronchoscope inserted through the mouth and throat, these lesions can be removed hemostatically, restoring the airway. This practice is used for benign growths and for palliative, but not primary, treatment of malignant neoplasms. UROLOGY Clinical application and investigational use of lasers in several urological conditions represent another outstanding example of minimally invasive surgery and the expanding impact of this technology. Bladder tumors that have not penetrated beyond the musculature of the bladder wall are treated with a minimally invasive technique through the natural urinary orifice. A view- ing cystoscope is inserted through the urethral opening into the fluid-filled bladder, where the lesion is identified and removed. The Nd:YAG, argon, and KTP/532 lasers have been used successfully in this procedure. All three wavelengths pass efficiently through the infused irrigating fluid. The Nd:YAG laser radiation penetrates and coagulates the lesion, which later sloughs off, and the radiation from argon and KTP/532 lasers vaporizes the mass. Higher 1 1

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LASERS IN MEDICINE ~ 1 5 energy densities are required for vaporization in this fluid milieu than in air because of heat transfer into the irrigant. Laser treatment of these lesions can be done under local anesthesia with the patient awake, whereas ablation with elec- trosurgical units is performed with the patient under general anesthesia because of attendant pain. This makes use of the laser particularly advantageous for the elderly, for whom other medical problems may make general anesthesia undesirable. Urethral strictures that are soft tissue obstructions that im- pede the flow of urine from the bladder can be vaporized with an argon or KTP/532 laser wavelength. Small urethral stones have been broken up by a fiber-optically delivered short pulse ( 1 ms, 10-100 mi) from a pulsed dye laser emitting in the green- yellow spectrum. This application is still being studied for safety and efficacy but is another potentially exciting and beneficial laser application in urology. ORTHOPEDIC SURGERY Lasers have been used clinically very little in orthopedic surgery. Orthopedic surgeons deal primarily with alterations of bone, cartilage, and ligaments. Currently used surgical lasers do not cut bone as well as other electrical and mechanical instru- ments. Although it is possible to cut bone with surgical lasers, they produce significant undesirable adjacent thermal destruc- tion. Investigators are now studying the technique of delivering lasers to the interior of the knee through an arthroscope that is inserted through a small puncture incision in the skin. This may prove a useful method for removing damaged cartilage. CARDIOVASCULAR APPLICATIONS The lure of using lasers in pursuit of the nation's number-one cause of death is strong, and many research efforts are under way in this area. Using an intravascular viewing catheter that holds a fiber-optic waveguide to approach and destroy an obstructive coronary artery lesion is an exciting concept the stuff that dreams are made of. Whether this is feasible by using a laser remains to be seen. A technique to eliminate intravascular lesions will be developed, but whether it will be laser based, electrical, mechanical, or some other combination of techniques is not clear. Several problems confound this development. Obstructive lesions are neither simple nor uniform. They may consist of a fresh clot; soft, multicolored atheromata; a hard,

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6 RODNEY PERK NS, M. D. calcified plaque; or a combination of these. The obstruction is irregular, and the restricted vessel lumen, if still present, is usually eccentric. The highly varied color and consistency of soft atheromata and arteriosclerotic plaque make it harder to predict a consistent effect of a laser. Undesirable thermal damage to vessel walls may cause subsequent vessel constriction, aneurysm, or perforation. At the same time, adverse thermal effects on the myocardial electrical conduction system must be considered. Investigators are also studying the question of whether the solid by-products of ablation could block vessels. All of these problems pose potential difficulties. Argon lasers are being used investigationally in attempts to vaporize obstructive lesions directly and to heat probe tips. Excimer lasers are being studied for use in plaque removal, but use of certain ultraviolet wavelengths is encumbered by delivery problems and the longer term mutagenic potential. Other wavelengths are undoubtedly undergoing evaluation for these purposes. Should these developments succeed, there will be a certain irony that a modality used first for its ability to close vessels should also be successful in opening them. Additional experimental work is being done to treat certain arrhythmias by precision photoablation of areas of the conduc- tive systems and to remove from heart valves any unwanted tissue that prevents them from closing adequately. The success- ful wedding of lasers with the recently developed intra-arterial catheter technology in cardiovascular applications could help considerably in mitigating the effects of one of our largest health care problems. PHOTODYNAMIC THERAPY The photoactivation of certain chemicals in viva has potential in the treatment of cancer. A dye material called hematoporphyrin derivative (HPD) is being activated by exposure to low-energy laser radiation with beneficial effects on certain malignant neo- plasms. Given to the patient about 48 hours ahead of the anticipated laser exposure, the HPD becomes intimately associated with malignant cells. Upon photoactivation of the HPD, a photo- chemical reaction causes the death of the malignant cell hosting the HPD but does not kill adjacent normal cells. Both 630- and 532-nm wavelengths are effective in activating HPD. The red 630-nm light penetrates farther into most tissues than the green 532-nm wavelength. However, 532-nm photo-

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LASERS IN MEDICINE ~ ~ 7 activation may be useful in bladder tumors, where the lesions are superficial and usually multicentric and can be exposed to the photoactivator wavelength delivered by a fiber-optic wave- guide with a diffusion tip. The development of other photoactive entities specific to different cancers might add new possibilities for the treatment of malignancies. At present, lasers have contributed significantly to the treatment of a wide variety of maladies. These applications and today's clinical lasers represent only the infancy of phototherapeutics. We will see other lasers evolve and take their places at the center of the clinical stage. Ultraviolet, diode, and free electron lasers all hold promise. Combinations of wavelengths, distributed both spatially and temporally, may provide tissue and surgical effects superior to those of single wavelengths. Miniaturization will enhance their usefulness. Instrumentation derived from combinations of photoelectro- nics and other core technologies will produce still more alterna- tives to standard surgical approaches. Exotic and more highly specialized delivery devices will expand the surgeon's ability to achieve precision therapy with low morbidity. Ultimately, these endeavors will advance minimally invasive surgery beyond our dreams. However, this achievement will be the product of human creativity and cooperation. The future of phototherapeutics will not be created by physicists, engineers, or surgeons alone but will become a reality only through the collective human resources of science, medicine, finance, and government working together with vision. TH E FUTU RE