The role of endoscopes in otologic surgery is growing as optical systems become increasingly sophisticated with smaller diameters and improved resolution. This author has performed 52 transtympanic middle ear endoscopic procedures in the office since 1990. Endoscopy, as a diagnostic procedure, was found to be a valuable technique yielding high quality examinations that eliminated the need for surgical exploration in all but one patient. Examinations were well tolerated, and no complications have occurred. It is anticipated that endoscopy will become an important technique for diagnostic middle ear exploration. Surgical intervention by endoscopy may prove useful in the future as dedicated otologic instruments become available, and laser systems are integrated.

This study investigated the use of a pulsed Holmium:YAG ((lambda) equals 2.09 micrometers ) laser- fiber microsurgical system for laser stapedotomy. This system ablates human stapes bones effectively with minimal thermal damage. The study was designed to determine the effectiveness of the Ho:YAG laser (Schwartz Electro Optics, Inc., Orlando, FL) for stapedotomy and to evaluate temperature changes within the cochlea during the ablation process. Human cadaveric temporal bones were obtained and the stapes portion of the ossicular chain was removed. A 200 micrometers diameter low OH quartz fiber was used to irradiate these stapes bones in an air environment. The laser was pulsed at 2 Hz, 250 microsecond(s) ec pulse width and an irradiance range of 100 - 240 J/cm² was used to ablate holes in the stapes footplate. The resultant stapedotomies created had smooth 300 micrometers diameter holes with a minimum of circumferential charring. Animal studies in-vivo were carried out in chinchillas to determine the caloric spread within the cochlea. A 0.075 mm Type T thermocouple was placed in the round window. Average temperature change during irradiation of the stapes footplate recorded in the round window was 3.6 degree(s)C. The data suggest that stapedotomy using the Ho:YAG laser can result in a controlled ablation of the stapes footplate with minimal thermal damage to the surrounding stapes. Optical coupling using fiberoptic silica fibers is an ideal method for delivering laser energy to the stapes during stapedotomy.

Stapedotomy is not only one of the most successful interventions in otology but also one of the most dangerous for the inner ear. To reduce the risk of damaging middle and inner ear structures through manipulations with conventional instruments, the CO₂ laser beam is used for perforating the footplate and removing the suprastructures. This non-contact technique aims at precise and controlled management of middle ear structures. Consideration is given to the impact of experimental data on the clinical application of the CO₂ laser in stapes surgery. The discussion covers the advantages and disadvantages with regard to optical and tissue-related properties and points out possible dangers to the inner ear. Our experimental and clinical experience is taken as a basis for examining the surgical technique and the varying demands made on the laser beam in treating the stapedial tendon, crura and footplate. Attention is called to the need for additional instruments. Effective energy parameters for CO₂ laser stapedeotomy are evaluated for different lasers. Application of the CO₂ laser contributes towards optimization of this high-precision intervention and promises to reduce the incidence of inner ear damages in large numbers of cases. This technique appears useful particularly in difficult anatomic situations and, above all, for revisional operations.

Endoscopy has become an important procedure in many medical specialties. For the Otologist, however, space limitations within the ear have restricted development of endoscopic procedures. The desire for minimally invasive techniques in Otology has demonstrated itself through the work of numerous physicians who have performed procedures ranging from diagnostic inspection of the middle ear to viewing the interior of the cochlea. To assist in performing such endoscopic procedures, Xomed-Treace has developed a line of flexible fiberoptic endoscopes for use by the Otologist. These scopes combine illumination and imaging fiber bundles within a small diameter unit ranging in size from 0.8 mm to 1.2 mm. The 1.2 mm scope is produced with an angled, rigid stainless steel sheath. The 0.8 mm scope is flexible with the ability to articulate 120 degree(s) in one direction. The fiberscopes have been designed for the Otologist to produce a good resolution image while allowing ease of operation through ergonomics and consideration of the surgical anatomy.

Endoscopy has revolutionized the field of medicine and surgery by aiding the clinician in diagnostic and therapeutic modalities of patient care. Endoscopy in Otolaryngology has provided the surgeon with unique access to areas of the head and neck which were previously inaccessible for direct inspection in an atraumatic and minimally invasive fashion. Specific areas of Otolaryngology where endoscopy has made advances are the rhinology and otology. The relevant anatomy, clinical requirements, and `state of the art' endoscopic techniques are discussed for these areas. Further advances in endoscopy for otolaryngology requires the cooperation from both the clinical and technical standpoints.

The Holmium:YAG laser was used to assist in 36 rhinologic procedures including surgery for chronic sinus disease, chronic dacryocystitis, recurrent choanal stenosis, and a sphenoid sinus mucocele. There were no laser related complications. The laser permitted controlled ablation of bone and soft tissue in all cases with satisfactory results. The Ho:YAG laser can be used in otolaryngology to assist in cases where surgical access is difficult or when controlled, precise bone and soft tissue ablation is necessary.

Pulsed Holmium:YAG (Ho:YAG) laser has been approved for some clinical applications and is under investigation for others. There is little published evidence on the durability or damage parameters for the fibers used in delivering energy from pulsed Ho:YAG laser. This study makes an initial attempt to investigate the damage threshold of different silica fibers under various conditions. Three types of fibers supplied by different manufacturers underwent laboratory testing. The overall finding of the study is that a new `perfect' fiber sustains no damage when fired without a target in air or in saline at energies up to 1.5 J/pulse and repetition rate up to 10 Hz. This study suggests that one may need to chose a fiber according to the clinical procedure to be performed: in cases where only soft tissue is to be manipulated - - any fiber may fare well, in cases where bone or calcified tissue is to be lased -- one may need fiber with aluminized or other hard coating. We also conclude that only professional refinishing with the removal of all exposed core-cladding material can insure trouble free performance.

Multiple centers in this country and throughout the world have documented the efficacy of Photodynamic Therapy (PDT) in the treatment of cancers of the tracheobronchial tree. While PDT can effectively achieve airway patency by treating bulky obstructing tumors, its most promising role for treating tracheobronchial cancers is in the treatment of superficial early stage tumors which can potentially be treated for cure with this technique. Unfortunately more widespread use of PDT awaits FDA approval which will be slow in coming due to the need for randomized controlled studies. Many improvements are needed in the thoracic application of the Nd:YAG Laser and PDT. However efforts to prevent lung cancer and detect early lung tumors may prove more beneficial than improvement of current systems which are all too often utilized on end stage tumors.

Interstitial laser phototherapy (ILP) is a technique whereby laser energy is directly applied into tumors at variable depths. This technique is attractive since it is minimally invasive and carries a low morbidity. ILP allows treatment of deep and difficult to reach tumors in the head and neck and other areas, since sensitive and non-invasive monitoring techniques of laser-tissue interactions are currently available. Recent studies have demonstrated, the efficiency of ultrasound (UTZ) and magnetic resonance imaging (MRI) for real time interstitial needle placement in tumors, identification of vessels, monitoring and quantifying laser-induced tissue damages. We now report an initial experience with patients in which MRI and/or UTZ guided ILP techniques were successfully applied for the treatment of recurrent, nonresectable, metastatic squamous cell carcinoma.

Methods of endoscopic documentation of the larynx have dramatically changed with advances in optical and video technology. With the introduction of laryngeal endoscopes with superb optics, compact light-sensitive CCD color video cameras and newer color video printers, it has now become possible to obtain high quality laryngeal pictures instantaneously from video images.

The results of laboratory testing and clinical use of pulsed solid state lasers in airway surgery are presented. Their advantages, limitations, interaction with tissue, current and future applications are discussed.

The CO₂ laser has been limited in its application within the tracheobronchial tree by its lack of a fiber delivery system. Recently a new product has been marketed, Luxar's flexible CO₂ laser waveguide or Flexiguide^TM, a spin-off of the presently used rigid waveguide or Microguide^TM. The study was undertaken so as to delineate the properties and thus the usefulness of this new product which promised an increased ease of delivery of the CO₂ laser wavelength. We compared the flexiguide with its rigid counterpart along two parameters. Specifically, we determined the total energy necessary to endoscopically resect bovine tracheal rings with each guide and then examined the histologic crater characteristics of each guide at a given energy setting. In so doing we endeavored to see if the experience of the surgeon with the microguide could be translated to the use of the flexiguide. We found the flexiguide to require a greater total energy than the microguide in the continuous wave (cw) and chopped pulse (cp) operational modes p < 0.01. There was, however, no demonstrated difference in required energy in the superpulse (sp) operational mode. Preliminary histologic evidence when measuring such indices as crater depth, crater width, and shoulder width thermal damage seem to suggest that the flexiguide is less efficient at tissue ablation than its rigid counterpart at the same given energy. It also appears to cause a greater degree of associated thermal injury.

A survey is currently underway as a joint venture of Lahey Clinic Medical Center and Laser Engineering, Inc. to establish a background of techniques and procedures using lasers in microsurgical otolaryngology. In September 1,000 ENT surgeons were surveyed. The survey consisted of questions related to their most common procedures and the techniques and instruments used in those cases. An analysis of the results of this survey is the basis of this manuscript.

CO₂ laser myringotomy has previously been proven effective in patients with serous otitis media for short term aeration of the middle ear. However, the system based on a microscope and a coaxially aligned laser is cumbersome and expensive. Also, conventional optical fibers do not transmit CO₂ laser energy ((lambda) equals 10.6 micrometers ). We have developed a silver halide optical fiber of diameter 0.9 mm and lengths of several meters, with high transmission at 10.6 micrometers . Using a hand held otoscope coupled to a fiberoptic delivery system CO₂ laser myringotomies were performed first in guinea pigs and then in humans. In the animal model the feasibility of the procedure was proven. Different irradiation parameters were studied and a `dose dependent' relationship was found between the total energy used and the duration of a patent myringotomy. This system was used to perform CO₂ laser myringotomies under local anesthesia in five patients with serous otitis media and conductive hearing loss. None of the patients complained of discomfort and no scarring was noted. All patients had subjective and audiometric documentation of hearing improvement. The average duration of a patent myringotomy was 21 days. In two patients the effusion recurred. CO₂ laser myringotomy utilizing a hand held otoscope coupled to an optical fiber capable of transmitting CO₂ laser energy may prove simple and effective in the treatment of serous otitis media.

The incident of tattoos in the United States is estimated to be in the range of 9 to 11% of the adult population. Various studies have shown that of these persons having tattoos, as many as 50 to 80% regret having gotten the tattoo and may desire tattoo removal. Previous treatment modalities have all used methods which require tissue destruction in order to remove the tattoo ink. The primary problems with use of these modalities has been the unpredictability of scarring. Also, residual tattoo pigment remaining after completion of the treatment process has been a problem. In response to these problems, the Q-switched lasers have been developed which target the tattoo pigments specifically rather than the tissue containing the tattoo pigment. The alexandrite laser (made by Candela Laser Corporation) has a wavelength of 755 nm and a pulse width of 100 nsec plus or minus 10 nsec. Reflectance studies have indicated that black, blue and green ink should absorb this wavelength relatively well, while red ink would not be expected to absorb this wavelength well. The mechanism of action of this laser is selective absorption of the laser energy by the tattoo pigment resulting in fragmentation of the pigment and then engulfment by tissue macrophages which remove the fragmented tattoo pigment. Preliminary studies using a Yucatan mini pig confirmed these expectations with black ink being easier to remove than blue and green, and red ink being minimally responsive. Higher fluences were more effective.

The ability of the Q-switched Nd:YAG laser (532 nm and 1064 nm, 10 - 20 ns, 10 Hz) and the Q-switched Ruby laser (694 nm, 40 ns) to remove pigmented epidermal lesions was assessed in 15 patients. Several lesions in the same general area were irradiated with varying fluences and wavelengths and the results of a single treatment session were compared. For the treatment of solar lentigenes, response was related to wavelength with greatest improvement (> 95% pigment removal) noted with the frequency-doubled QS Nd:YAG laser (532 nm) at 4 or 5 J/cm². Mild, transient erythema, hypopigmentation, and less commonly, hyperpigmentation were noted with the QS Nd:YAG at 532 nm and the QSRL. No other side effects including leukotrichia, textural changes or scarring were noted.

A Q-switched frequency-doubled Nd:YAG dye laser, configured to emit light at 577 nm, was used to study the effect of nanosecond pulsed light on vascular tissue. The pulse width of this light is approximately 10 nanoseconds and the pulse repetition rate is, at most, 10 Hz. A rat dorsal skin-flap window-chamber model, a colon (cecum) model, as well as an isolated femoral vessel model were used to study the effects on vascular tissue of irradiation with single laser pulses using fluences ranging from 0.2 J/cm² to 3 J/cm². Different reactions such as vasospasm, vessel expansion, and vessel rupture were observed. A correlation between increasing fluence and increased vascular damage was noted. When it occurred, vessel rupture was seen on the superior side (i.e. the irradiated vascular surface) as well as on the inferior side of the blood vessel. The inferior side damage was verified on histological examination. This damage pattern was thought to be most likely caused by shockwaves, and photoacoustic measurements were performed that support this hypothesis.

Development of a small spot (100 microns) technique using very low powers (0.1 - 0.4 watts) continuous output by A. Scheibner M.D. in the early 1980's virtually eliminated scarring which made it possible to treat not only children with portwine stains but also cosmetic problems such as capillary telangiectasia for which treatment was previously not available. Improvement of scars was also observed to occur with this treatment in 1983. However, very specific adjustments were required to produce consistent improvement of scars.

The application of pulsed photothermal radiometry (PPTR) diagnostics to characterize port wine stain (PWS) lesions is discussed. A PPTR signal of a PWS in response to pulsed laser exposure is shown to consist of an initial `T-jump' due to epidermal melanin absorption and a `delayed thermal wave' resulting from laser generated heat in subsurface blood vessels diffusing to the skin surface. A prototype PPTR instrument incorporating an infrared fiber is constructed which facilitates convenient skin-site accessibility. Laser heating of the infrared collection optics results in an artifactual signal which overestimates the initial `T-jump.' Magnitude of the error is measured and a method to eliminate it is suggested.

The autofluorescence distribution of excised skin tissue sections were studied using a novel microspectrophotometer (MSP) system developed in our laboratory. The MSP consists of a microscope, an Optical Multichannel Analyzer (OMA), and a PC computer. Skin samples were placed on a glass slide for microscopic examination. A 442 nm He-Cd laser beam was used for fluorescence excitation and autofluorescence images were detected and recorded by a CCD camera. An optical fiber was mounted into the image plane of the microscope both to collect light from a specific micro-location in the sample for spectral analysis and to conduct light in the reverse direction into the microscope for alignment purposes. Examination of 24 human skin sections revealed that the dermis had a strong fluorescence emission, the stratum corneum had a weak fluorescence signal, while the remaining epidermis fluoresced with only a faint signal. The color of the fluorescence from the upper dermis and the lower dermis were different. Spectral analysis using the MSP showed that the positions of the autofluorescence spectra maxima from the upper and lower dermis differed by 20 nm suggesting that fundamentally different fluorophores may be present in the respective tissue layers. The border between the two different autofluorescence color areas was located approximately 480 micrometers below the dermal-epidermal junction. Whether this is the border between the papillary dermis and the reticular dermis has yet to be determined.

Experiments on the determination of the possibilities of laser fluorescent spectroscopy for detecting the spatial distribution and time of presence of methoxypsoralens in human epidermis have been carried out.

The broad, long term objective of this work is the development of Photodynamic Therapy (PDT) for application in the clinical management of patients with port wine stain (PWS). PDT involves the use of an exogenous drug which is concentrated in a targeted tissue. When irradiated at wavelengths specifically absorbed by the drug, selective destruction of the targeted tissue, without the production of heat, occurs. The results of this preliminary study demonstrate in human PWS patients that a photosensitizer, such as PHOTOFRIN^R, activated by red light at the appropriate therapeutic wavelength, can cause destruction of subsurface blood vessels in the skin with a high degree of specificity, and further study appears warranted.

The ProClosure^TM System (PCS) consists of a low power 1.32micrometers Nd:YAG laser coupled to a handheld disposable fiber optic device. The system has been designed to perform a wide range of tissue welding applications such as cosmetic skin closure,vascular surgery, and minimally invasive surgical procedures normally performed with sutures and staples. Utilizing a wavelength for tissue fusion that is least distracted by medium in the surgical field coupled with a computerized delivery system allows for a more precise application (+/- 5%) of laser energy to the tissue. The study design involved the micro-surgical anastomosis of twenty Sprague-Dawley rats (vas deferens) and twenty-one Sprague-Dawley rats (femoral arteries). Each rat is its own contralateral control. Laser repair time is approximately one-third that of conventional suturing. Postoperative dissection and burst strength testing was conducted at day 0, 1, 7, and 14. At each postoperative interval, the mean leak/burst strength for laser-assisted closure v. control, was markedly higher. The precise application of energy fluence resulting from ProClosure's computerized system yields an initial strength and a fluid static seal that is superior to conventional suture closure.

Despite success with autologous tissue welding, laser welding of synthetic vascular prostheses has not been possible. The graft material appears inert and fails to allow the collagen breakdown and electrostatic bonding which results in tissue welding. In order to develop a laser welding system for graft material, we repaired gluataldehyde-tanned human umbilical cord vein graft incisions using laser-assisted fibrinogen bonding (LAFB) technology. Modified umbilical vein graft was incised transversely (1.2 cm). Incisions were repaired using sutures, laser energy alone, or LAFB. In vivo evaluation of umbilical graft bonding with canine arteries demonstrates that LAFB can reliably reinforce sutured anastomoses. The described system for bonding graft material with laser exposed fibrinogen may allow creation or reinforcement of vascular anastomoses in procedures where use of autologous tissue is not feasible.

Anastomotic leakage or breakdown can result in catastrophic complications and significantly increased post-operative morbidity and mortality. Certain anastomoses are subject to a higher incidence of disruption and are therefore termed high risk. In an attempt to decrease the risk of anastomotic leaks, we reinforced sutured anastomoses with a laser activated protein solder in patients undergoing esophagojejunostomies (n equals 2), lung transplantation (n equals 2), and pancreaticojejunostomies (Whipple procedure, n equals 5). The protein solder was composed of 1.0 ml of a 25% human albumin solution, 1.0 ml of sodium hyaluronate, and 0.1 ml of Cardiogreen dye. This composition was applied to the sutured anastomosis and activated with an 860 nm pulsed diode laser. Drains were placed when appropriate and patients were followed for up to 10 months post-operatively and assessed for clinical signs of anastomotic leaks. Results to data demonstrated that there were no immediate complications as a result of the procedure. Operative time was not significantly lengthened. There were no cases of clinically significant leakage from any of the reinforced anastomoses. Laser activated protein solders may help to reduce the incidence of leakage in high risk anastomoses. Large numbers of patients and longer follow-up is needed however, to draw significant conclusions.

One future use of laparoscopic technology is in extravesical reimplantation of the ureters. Technical difficulty arises, however, when intracorporal fine suturing is necessary. We have assessed the efficacy of laser-activated fibrinogen solder to close vesical muscle flaps over submucosal ureters (Lich-Gregoir technique) in a canine model. Four dogs were subjected to unilateral flap closures via a protein solder consisting of indocyanine green and fibrinogen applied to the serosal surface of the bladder and exposed to 808 nm continuous wave diode laser energy. Contralateral reimplantation was performed using 4 - 0 vicryl muscle flap closures and served as controls. Urinary drainage catheters were left in place for 24 hours postoperatively. At 7 (n equals 1), 14 (n equals 2), and 28 (n equals 1) days following reimplantation, intravenous pyelograms confirmed bilateral renal function and ureteral patency. Disruption of wound closures were considered the point of wound dehiscence, vesical diverticulum, or leakage. At intravesical pressures above 100 cm H₂O there was no evidence of wound disruption in either of the groups. However, surrounding normal tissue was noted to disrupt. In conclusion, laser-welded vesical wound closures appear at least as strong as suture closures in the canine model.

We have newly designed and synthesized a class of photochemical 1,8-naphthalimide dyes. Photochemical investigation strongly suggests that these dyes function as photoalkylation agents following activation to an intermediate state by visible light (circa 420 nm) excitation. The activated species reacts readily with nucleophilic amino acid residues; e.g., tryptophan, tyrosine, cysteine, and methionine. One such dye, 1,14-bis(N-hexyl-3'-bromo- 1,8'-naphthalimid-4'-yl)-1,4,11,14-tetraazatetradecane-5,10-dione, incorporating two reactive 1,8-naphthalimide groups at each end of an intervening structural bridge has been used to achieve photochemical or photoactivated bonding (welding) of collagenous dura mater sheets to each other. Weld shear strengths of up to 425 gm/cm² (1.14 X 10⁴ Nt/m²) have been obtained.

Thermal fusion or welding of collagen-rich tissues involves the thermal denaturation of collagen which is reflected by changes in birefringence intensity in histologic sections. The weld bond between two severed edges is formed when the apposed ends of the collagen fibrils unravel during heating then re-entwine during the cooling phase. Thermal coagulation of collagen can be described as an end point of a kinetic rate process of thermal damage which is linear with time of exposure and exponential with temperature. The kinetic rate coefficients, A (s^-1) and E (J/mole), have been experimentally determined for birefringence loss in rat skin collagen heated in vitro -- A equals 1.606 X 10⁴⁵ and E equals 3.06 X 10⁵. Loss in collagen birefringence is a rare quantitative indicator of thermal damage; in this case, the structural alteration in tissue native-form collagen. The kinetic model coefficients were derived from exposure times between 600 and 6000s over the temperature range 45 to 90 degree(s)C. Room temperature control specimens were also analyzed for comparison.

A UV-laser microbeam was successfully used to induce fusion of early embryonic cells. The developmental capacity of the laser-fused cells was examined using in vitro culture methods. Blastomeres within mouse two-cell embryos were fused with 3 - 10 subsequent laser pulses in order to produce tetraploid embryos. Thirty-one percent of the laser treated embryos fused and 10% of those developed to the morula or blastocyst stage. With 1 - 10 successive laser pulses cattle oocytes were fused with cytoplasts. Thirty-six percent of the laser treated cells fused and 10% of those cleaved to the 6- and 8-cell stage. These preliminary results indicate that a UV- laser microbeam combined with an optical tweezers may facilitate the manipulation of embryonic cells and can be a helpful tool in polyploidy studies and in cytoplasmic transfer experiments.

A 1.9 micrometers laser is used to weld small diameter vessels. The absorption characteristic of tissues at this wavelength renders this laser suitable for welding of vessels with diameters in the 1 to 3 mm range. The appropriate laser power range for welding is 120 to 200 mW with a fluence on target of approximately 100 J/cm². For vessel wall thicknesses matching the optical absorption depth, measured burst pressure was approximately 400 mmHg. In this case the acute weld strength is greater than 3 X 10⁶ dynes/cm². Anastomotic compliance of the welded zone was a factor of two lower than native vessel tissue both immediately following welding and after 10 weeks of healing. The advantages offered by this laser wavelength are convenient energy delivery via fiber optics, no irrigation needed for tissue cooling, and applicability to small vessel anastomoses.

Laser welding of tissues is an experimental surgical technique for the binding of tissues. The difficulty in the clinical implementation of this technique arises from the difficulty in defining the optimal conditions under which a satisfactory weld is formed. Temperature measurements of laser irradiated tissues are difficult to perform and experiments have produced conflicting results. Fiber optic radiometry allows temperature measurement of laser irradiated tissues by remote sensing of emitted infra red (IR) radiation. We developed an IR radiometer capable of accurate temperature measurements (+/- 0.2 degree(s)C). Utilizing this radiometer for the monitoring and control of CO₂ laser irradiated tissues we achieved temperature control of +/- 2.5 degree(s)C of tissues during welding. This system was used to perform laser welds on the urinary bladders of rats. The strength of the welds was recorded for different welding temperatures, and maximal strength was obtained at 55 degree(s)C and 12 sec.

This is a preliminary report of an ongoing clinical trial involving patients with malignant skin tumors. Fifteen patients with malignant skin tumors received an infusion of 0.25 - 0.5 mg/kg of BPD-MA three to four hours prior to irradiation of their tumors with 50 - 150 J/cm² of 690 nm laser light from an argon pumped tunable dye laser. Tumor response was assessed clinically for up to three months following treatment. In addition, daily serial phototesting of normal skin to filtered light from a xenon arc lamp emitting UVA and visible (UVA/VIS) light was carried out before and after BPD-MA infusion to determine the dose of light required each day to produce `minimal erythema' in normal skin. Complete follow-up data are available for 64 cutaneous tumors in the first fifteen patients treated. A complete clinical tumor response was noted in 63% of the tumors treated, with a partial response (> 50% reduction in tumor area) in 11%. Sensitivity to UVA/VIS light was drug dose-dependent and maximal on the day of treatment. The estimated mean duration of photosensitivity to UVA/VIS light ranged from 2.4 days for the lowest BPD-MA dose (0.25 mg/kg) to 5.4 days for the highest dose (0.5 mg/kg). Cutaneous photosensitivity due to BPD-MA appears to be short-lived. Complete responses for malignant skin tumors have been achieved using BPD-MA doses of 0.25 - 0.5 mg/kg in combination with 50 - 150 J/cm² of 690 nm laser light.