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УДК 618.16: 615.849
PHOTODYNAMIC THERAPY IN TREATMENT OF PATINETS WITH DYSTROPHIC DISEASES OF THE VULVA
Republican Specialized Scientific-and-Practical Medical Center of Dermatology and Venereology, Tashkent V.Vakhidov Republican Specialized Centre of Surgery, Tashkent Irkutsk State Medical University, Irkutsk
D.F. Porsokhonova, R.R. Sadykov, A.I. Yakubovich, M.R. Mukhamedova, S.N. Rakhmatullayeva
The article contains the results of a comparative use of two different methods for the treatment of dystrophic diseases of the vulva: photodynamic therapy and diathermocoagulation. To assess the effectiveness of therapy, patients with lichen sclerosis, hyperplastic dystrophy and combined dystrophy were divided into two clinically comparable groups. The method of photodynamic therapy consisted in irradiation of the affected areas with the Vostok-Delta-03 apparatus 3-6 hours after the external application of the photosensitizer in an amount up to 10 ml with a gel concentration of 5% without anesthetic protection. Light exposure was carried out in a pulse mode; the duration of irradiation was 20-45 min. The wavelength of radiation was 630 nm, the laser radiation power at the end of the fiber was 100 mW, and the energy density was 100-250 J / cm2 for the vulva. In the comparison group with patients with hyperplastic dystrophy, the electrocoagulant was used to destroy the pathological sites with the help of the ECHVCH100 apparatus (Uzbekistan). As a result of the use of PDT, high treatment efficacy, antiviral effect, and the absence of undesirable side reactions were achieved. In this connection, the PDT method can be actively introduced into the practice of treating genital dystrophy.
Key words: photodynamic therapy, lichen sclerosis, dystrophic diseases of the vulva.
The problem of dystrophic vulvar diseases (DVD) which include lichen sclerosis (syn. sclerotic), hyperplastic dystrophia, combined dystrophia and other types of dermatosis, has becoming particularly significant in recent years due to a considerable juvenation and frequent canceration [1, 12]. The risk of malignant tumour development in this category of patients, according to various data, constitutes from 9 to 49% [11, 13]. Though not always the dermal process is treated as the background one, however, it is not possible to visually predict the disease outcome without special methods of examination [2, 8]. Hyperplastic dystrophia is characterized by dermal thickening, but phimosis vaginalis is practically not registered. By lichen sclerosis the skin becomes thin, folds thicken and, as a rule, vaginal orifice shortly coarcts. Combined dystrophia occurs in 15% of cases and is characterized by the presence of symptoms of hyperplastic dystrophia and areas with lichen sclerosis [5, 9, 10]. The variety of causes leading to dystrophia make this problem interdisciplinary and complicates the process of diagnostic search and, consequently, treatment.
By the present time, there are no reliable data on the efficiency of conservative methods of the mentioned disease treatment [4, 7]. The use of hormonal ointments and creams by patients frequently leads to the tissue atrophy and formation of acquired tolerance and addiction. Later the steroid therapy becomes inefficient. Surgical treatment, in spite of higher efficiency, is characterized by high injury rate, intensive postoperative pains, high frequency of postoperative complications, unfavorable cosmetic and functional results [3, 6, 14].
Research objective: to study the efficiency of photodynamic therapy in treatment of patients with dystrophic diseases of the vulva in relation to traditional methods.
Materials and methods
Totally, there were observed 31 female patients with DVD. According to the type of revealed pathology patients were divided into the following way: 22 patients (71,0%) had lichen sclerosis and 5 (16,1%) - hyperplastic vulvar dystrophia, 4 (12,9%) - combined dystrophia. As a rule, patients had been suffered from the given pathology from 3 to 22 years. The duration of postmeno-pause period ranged from 2 to 27 years. To specify the nature of the revealed pathology women were exposed to the examination of vulvar scrape, vul-voscopy, PCR-diagnostics to reveal cancerogenic types of human papilloma virus (HPV), and also the histology of the biopsy material from pathological areas. Pathomorphological examinations after the fixation of tissue fragments in 4% formalin solution on phosphate buffer (pH 7,6) and tissue embedding in the wax by Z.Loid (1982) were performed at the Department of pathological anatomy and forensic medicine of TashlPME (Head of the Department: Mavlyankhodzhayev R.Sh.). In 12 patients there was revealed the HPV of type 16, 18 (38,7%), in 6 patients - HPV of type 31, 33 (19,4%), in 2 (9,7%) there was revealed the carriage of low cancerogenic HPV types, in 10 (32,3%) patients HPV was nor registered.
In order to reach the stated goal patients were divided into two clinically comparative groups. The main study group included 13 women with
DVD at the age from 19 to 67 years (average age 45,6 ± 3,2). The comparison group constituted 18 women with DVD at the age from 32 to 65 years (average age 41,8± 4,1).
The clinical picture of the disease was mainly presented by infiltrative plaques and also by thinning and thickening of tissues with typical white shade of skin and mucous membrane of labia minora and majora, clitoris and vaginal orifice. In some patients the process spread over the whole vulva, perinatal area and internal hips. In 8 (25,8%) patients there were registered cases of depigmenta-tion caused by constant scratching. In the examined patients there was revealed extragenital pathology of various intensity. In half of patients (53,1%) there prevailed impaired fat metabolism, hypertensive disease, varicose vein disease of lower limbs (31%), atherosclerosis of various intensity (26%). Chronic bronchitis, gallstone disease, chronic pancreatitis were diagnosed in 7 (22,6%) patients, chronic tonsillitis and neurocirculatory dystonia - in 3 (9,7%); hepatic steatosis, kidney stone disease - in 3 (9,7%), chronic gastritis, nodular goiter, diabetes mellitus of 2nd type and chronic pyelonephritis - in 7 patients (22,6%). No significant differences between the frequency and intensity of concomitant pathology in the studied group were revealed.
All patients were exposed to the complex clinical examination including bacteriological, endo-visual (colposcopy), histological and cytological methods. The morphological examination of biopsy materials of vulvar mucose membrane in patients with DVD.
The following changes of varying severity in the tissue were diagnosed in patients with DVD during the morphological examination of the biopsy materials of vulvar mucose membrane: thinning of the epidermis with the normal stratum corneum, hyper- and parakeratosis; the presence of active proliferation of the epidermis; a smoothed papillary layer; altered nuclear structures of the epidermis in the form of augmentation of the nucleus, multinucleation of cells; thickening and swelling of elastin and collagen fibers in the stroma; leukocyte infiltration; single koylocytes, lymphocytic infiltration, epithelial dysplasia of I-II degree.
Indication for the procedure of PDT was a verified diagnosis of dystrophic processes of the skin and vulvar mucosa. In the preoperative period, patients with infection of the genital tract had antimicrobial therapy and immunocorrection, followed by measures to normalize the vaginal microbio-cenosis.
Laser exposure, as a rule, was performed in the first phase of the menstrual cycle, in 3-6 hours after local application of the combined photosensi-tizer (PS) on the basis of natural and phenothiazine photosensitizers in the form of 0.5% gel. The irradiation was carried out with the aid of the diode laser apparatus "Vostok Delta-03" (Uzbekistan).
The radiation wavelength is 660 ± 15 nm, the energy density is 100-200 J / cm2, and the exposure time is from 10 to 20 minutes.
In order to select the optimal time parameters for the onset of irradiation, corresponding to the maximum accumulation of PS in the mucosa and skin, a method of estimating the local fluorescence was used with the help of the AFD-1 spectral-fluorescent diagnostic apparatus (Uzbekistan). Radiation of a wavelength of 400 ± 10 nm was used for the induction of fluorescence, which made it possible to selectively excite the fluorescence of the PS. The measurements were performed prior to the administration of FS (autofluorescence evaluation) and 3 and 6 hours after application of PS to the skin and mucosa (induced tissue fluorescence). During spectral-fluorescent studies, it was determined that if the endogenous fluorescence of the mucosa was insignificant before the administration of PS, after injection of PS at all measurement points, the induced fluorescence was expressed with a sufficiently bright glow. The output power from the FDU-1 apparatus was up to 30 mW, the exposure time was up to 100 ms. The maximum values of fluorescence, and, consequently, the accumulation of PS, were recorded in the skin 6 hours after application to the skin. The optimal time to start treatment with PDT was the maximum value of the fluorescence of pathological tissues.
According to the procedure No.1, the irradiation session was performed by the Vostok-Del-ta-03 apparatus 3-6 hours after external application of FS in an amount up to 10 ml with a gel concentration of 5% without the use of anesthetic protection. Light exposure was carried out in a pulsed mode; the duration of irradiation was 20-45 min. To determine the absorption coefficient, there were made measurements of the power of the light flux at the exit from the end of the radiator, and then at the same laser power the light flux from the surface of the skin (reflected radiation) was measured as well. The degree of absorbed radiation by the tissues was determined by the difference in indices. The wavelength of the radiation was 630 nm, the laser radiation power at the end of the fiber was 100 mW, and the energy density was 100-250 J/cm2 for the vulva. In the comparison group, according to the procedure No.2 the destruction of pathologic sites with an electrocoagulator was used in patients with DVD with the help of EHVCH100 apparatus (Uzbekistan).
Results and discussion
Analysis of treatment results was conducted in 31 patients with DVD. The therapeutic effect of PDT with 13 patients was assessed visually and on the basis of indications of the presence or absence of pruritus in the vulva area; this effect was also confirmed by data of morphological examination and vulvoscopy. Thus, the disappearance
of pruritus in the vulva region was noted in 7 of 9 patients with vulvar lichen sclerosus. All patients with hyperplastic dystrophy and mixed dystrophy underwent a cytological study of vulvovaginal scraping and vulvoscopy, on the basis of which the clinical cure was reliably diagnosed. The antiviral effect of PDT was evaluated after repeated PCR with DNA typing of HPV from the vulva surface. As a result of our findings, HPV was not found in any patient. Adverse reactions consisted only in a minor pain syndrome after the procedure of PDT and body temperature rise in four patients during the first 2-3 days after the procedure, which were jugulated by the intake of non-steroidal anti-inflammatory drugs. Complete clinical remission in the 1st group was observed in 11 patients (84.6%). 2 patients (15.4%) with vulvar lichen scle-rosus underwent a second session of PDT, after which a clinical cure was diagnosed. The patients were observed within 12 months after a PDT session; the relapse was observed in no case.
When analyzing the inflammatory processes of the vaginal mucosa after PDT, there was observed the formation of a thin scab in the irradiation zone 24 hours after the procedure. The beginning of marginal epithelization of the eroded surface was observed on the 5th-8th day in the absence of leukocyte infiltration. Complete epithelization was detected in 4-7 weeks, whereas in the comparison group the average epithelialization completion time was 5-10 weeks. With the use of PDT in 2 patients, there was observed incomplete epitheliza-tion of the vaginal mucosa after 8 weeks, which required the repeated conduct of the PDT session, which resulted in a positive clinical effect.
The patients who underwent electrocoagula-tion demonstrated complications with a greater frequency. 17 patients suffered from severe pain within 3 weeks, requiring the taking of pain killers. Pregnant secretions throughout the period of repair were noted in 6 patients. Exacerbation of the inflammatory process of the uterine appendages was observed in 4 patients, exacerbation of colpitis was noticed in 6 patients, and 5 patients showed incomplete epithelization of the vaginal mucosa for 6 weeks.
According to the data of cytological and col-poscopic studies, clinical effect was achieved in 17 (94.4%) patients. The antiviral effect was significant in 8 patients with antiviral and immunostimulat-ing therapy. The study of long-term results after electrocoagulation (after 6-9 months) revealed that the pain syndrome was troubling 4 patients, 5 patients suffered scar deformity, and the recurrence of the disease was noted in 3 patients.
Conclusion
Treatment of dystrophic diseases of female external genital organs of non-tumorous genesis by PDT method with the use of combined FS demonstrat-
ed its high therapeutic efficiency. A positive antiviral effect against HPV was achieved. Side effects and complications during treatment were minimal. The PDT method is distinguished by its selectivity, as well as by sparing effects on pathological tissues. The procedure of PDT is well tolerated, does not require the use of strong pain-relieving medications. The postoperative period goes, as a rule, without complications with a fairly rapid restoration of work capacity.
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Contacts:
The author responsible for correspondence - Por-sohonova Delya Fozilovna, MD, Ph.D., head of the Department of STI and Reproductive Health of the Republican Specialized Scientific-and-Practi-cal Medical Center of Dermatology and Venereol-ogy, Tashkent
100009, Tashkent, Almazar district, Farooby St., 3.
Tel.: 998 (71) 2145098.
Email: [email protected]
