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Biomedical subjects

R Marchesini

Publications and source records attributed to R Marchesini.

At least 55 records · Page 3Linked to original sources

Increasing incidence of cutaneous melanoma, ultraviolet radiation and the clinician.

Incidence of melanoma is certainly rising all over the world and this observation has been related to a more frequent and prolonged exposure to the rays of the sun. The authors critically review pertinent literature and conclude that descriptive epidemiology of melanoma does not give survival trends and does not support the claim that melanoma is ultraviolet (UV) dependent. Analytical epidemiology has not reached a consensus on this aspect. Experimental data available are also difficult to interpret because there are consistent differences of susceptibility to UV among different animals, among lamps used and methods of measuring employed in various laboratories. Information available shows that the maximal relative biological activity of UV in humans is at about 305 nm. This evaluation greatly depends on (1) thickness of the skin, (2) the quantity and quality of secretions that cover the skin, (3) cleanness of the skin, (4) the latitude, (5) the weather, (6) the hour of the day and (7) the presence of chemical carcinogens in the air and on the skin. The authors stress the importance of the criteria of clinical diagnosis recently introduced in clinical practice and higher public awareness as the causes of the increasing incidence of melanoma.

Animals↗

Topical administration of tetrasodium-meso-tetraphenyl-porphinesulfonate (TPPS): correlation between drug penetration and depth of necrosis in skin of nude mice following red light irradiation.

The main side effect in photodynamic therapy is photosensitization of the patient's skin following systemic administration of the photosensitizing agent. In the case of superficial lesions, this problem can be avoided by topically applying the drug: in this way a local treatment can be performed. We tested the photosensitizing properties of a 2% solution of TPPS (tetrasodium-tetraphenylporphinesulfonate) in a vehicle containing a penetration enhancer, Azone, on skin of nude mice. An aliquot of 0.1 ml/cm2 of the solution was painted on the skin overlying an s.c. implanted NMU-1 tumor. Subsequently, animals were sacrificed at different times after application. Fluorescence microscopy revealed that TPPS penetration depth was related to time elapsed after application and to painting modalities. Solution penetration was enhanced by wiping with ether immediately before painting. Irradiation at 80 mW/cm2 for 20 min with a dye laser emitting at 640 nm, 4 h after TPPS application, produced necrosis of the upper skin layers, up to 0.2 mm in depth. These findings suggest that topical TPPS administration, followed by laser irradiation, may be a suitable treatment modality for skin lesions involving epithelial layers, even though several aspects of this metodology need further investigation.

Adenocarcinoma↗

Topical administration of tetrasodium-meso-tetraphenylporphinesulfonate (TPPS) and red light irradiation for the treatment of superficial neoplastic lesions.

In photodynamic therapy, systemic administration of photosensitizing agents induces cutaneous photosensitization in patients. This side-effect can be avoided by topical administration of the agents when only surface lesions are involved. A hydroalcoholic solution of tetrasodium-meso-tetraphenylporphinesulfonate (TPPS) containing Azone, a percutaneous penetration enhancer, was investigated to evaluate its photosensitizing potential in the treatment of 33 primary and recurrent neoplastic lesions of the skin. A complete remission was obtained of lesions with clinical thickness of less than 2 mm. Treatment effectiveness depends on both light and drug penetration through skin. Further studies are in progress to optimize treatment parameters.

Administration, Topical↗

Preliminary clinical studies with PDT by topical TPPS administration in neoplastic skin lesions.

Cutaneous photosensitization by topical administration of a porphyrin derivative has been previously reported from experimental studies. Preliminary clinical trials performed at the National Cancer Institute of Milan in the last six months have confirmed the feasibility of treating skin lesions by topical application of photosensitizers. Fourteen cases of basal cell carcinoma were treated by local administration of tetraphenylporphinesulphonate (TPPS), vehicled by azone. Later, the tumor was exposed to a wavelength of 630 nm from a dye laser. We noted complete remission, as documented by biopsies, in all tumors, with clinical thickness less than 2 mm, whereas partial remission was obtained in tumors with clinical thickness more than 2 mm. Our experience suggests the possibility of a routine treatment by this method for flat basal cell carcinoma and pre-malignant lesions, with remarkable advantages to conventional therapies. Our results have to be confirmed by increasing the number of cases and length of follow up; our short follow up does not allow us to make definitive claims regarding this therapy.

Administration, Topical↗

Laser microsurgery in oncology: indications, techniques, and results of 5-year experience.

Multidisciplinary collaboration has enabled us to use the CO2 laser in many different surgical fields. The 5-year experience at the National Tumor Institute of Milan is reviewed for the evaluation of short- and medium-term results of 321 laser surgical operations of the lower genital tract, 475 cases of lesions of the larynx and oral cavity, and 246 cases of skin lesions. A unified approach was used as regards safety measures, preoperative evaluation, and rules of application of laser instruments. The reliability of the surgical procedures, the proper selection of the cases, and the low rate of postoperative complications allowed outpatient treatment in 76% of the cases, thus reducing the hospitalization costs. The use of the microscope for laser resections under magnification was recognized to be preferable in routine surgical oncology practice. Short- and medium-term clinical results with laser microsurgery were comparable to those with conventional surgery, especially when precise and conservative removal of periorificial lesions was required.

Equipment Safety↗

Laser microsurgery for superficial lesions of the penis.

A carbon dioxide laser microsurgical technique for partial or complete resection of superficial lesions of the penis is described. This technique was used in 47 patients from January 1982 to May 1985. Of the 47 patients 32 (68 per cent) were treated on an outpatient basis. Histological study of the lesions showed microscopically invasive cancer in 8 patients, carcinoma in situ in 4, grades II and III dysplasia in 5, hyperkeratosis or parakeratosis in 10, pigmented lesions in 2, papilloma in 1 and no residual disease after systemic chemotherapy for exophytic carcinoma in 3. Laser surgery was performed in 1 stage under constant microscopic visual control. The depth of the resection ranged from 0.5 to 2.6 mm. (mean depth 1.5 mm.). Surgical specimens were fit for a correct pathological examination when they were thicker than 0.5 mm. (95.7 per cent of the cases). Microscopically, the margins of the resection resulted in healthy tissue in 41 of the 45 evaluable specimens (87.2 per cent). The mean distance between the lesion and incision borders was 0.6 mm. (range 0.4 to 1 mm.). Of the 4 patients with microscopic evidence of disease at the resected margins 3 underwent another laser microsurgical procedure and 1 received external beam radiation. Healing by secondary intention had an average duration of 6 weeks. Cosmetic results were satisfactory in every patient. Only 1 patient (2 per cent) suffered complications (arterial hemorrhage). In conclusion, the short-term results of this surgical technique for penile lesions are satisfactory. Further followup is needed to evaluate the curative potential of this method.

Adult↗

Excision of oral leukoplakias by CO2 laser on an out-patient basis: a useful procedure for prevention and early detection of oral carcinomas.

Several epidemiologic studies have shown that oral cancer develops among individuals with a prior diagnosis of an oral premalignant lesion. Canceration chance in these patients is 17%, with the greatest rate occurring in the second year of observation. Based on this data, since 1981, 92 leukoplakias have been treated by out-patient laser surgery at the Istituto Nazionale Tumori of Milano. The therapeutic technique was laser excision to obtain a specimen for histology. Two groups were distinguished according to the diagnostic procedure. Thirty-three lesions (December 1981 to December 1982) were operated on without preliminary histologic examination, on the basis of a simple clinical diagnosis. Since January 1983 all leukoplakias have been biopsied in a systematic way and those negative for cancer treated with laser. Histology of the specimen showed 5 squamous cell carcinomas (15%) in the group of patients who did not undergo preoperative biopsy. Postoperative histology showed malignancy in 6 of 59 (10.2%) cases in spite of negative preoperative biopsies. Speckled and erosive leukoplakias had the highest canceration rate. Three of 11 patients with cancer were treated by knife excision or interstitial needle implantation because of margins in tumoral tissue or because they were not evaluable for injury by heat. Results have been satisfactory, only 2 of 54 followed leukoplakias and none of the cancers recurred during a 2 year follow-up.

Adult↗

A study on the possible involvement of nonlinear mechanism of light absorption by HpD with Nd:YAG laser.

The purpose of this study was to investigate whether excitation of porphyrin could be related to nonlinear mechanisms of absorption of porphyrin itself or of the medium in which porphyrin is embedded. This possibility was proposed as an explanation for results of previous experiments where a Nd:YAG laser was used. An MS-2 sarcoma transplanted into the hind pad of BALB/c mice was used as the experimental tumor model. Mice were given HpD i.v. (25 mg/kg) 24 h before exposure to light delivered from an IR laser (1,060 nm). Since at dose-rates ranging between 600 and 1,200 mW/cm2 the thermal effect tended to mask the nonlinear effect, the temperature of the limb of mice was kept cold by running water. Irradiation performed under cooling conditions did not show any tumor growth inhibition. Experiments in vitro performed on HT-29 cells by a continuous wave (CW) or pulsed (Q-switch) Nd:YAG laser indicated no appreciable difference in DNA synthesis between irradiated and nonirradiated cells. Our results did not evidence nonlinear mechanisms of absorption by HpD with Nd:YAG laser both in CW and pulsed (nanosecond range) modes. Whether this effect should occur, in any case it is unlikely to be suitable to induce a photodynamic effect due to its low efficiency. Nd:YAG laser could induce a heating related effect, which can improve the therapeutic efficacy of PDT.

Animals↗

Temperature rise in biological tissue during Nd:YAG laser irradiation.

Few data are available about temperature distribution in tissue during Nd:YAG laser irradiation. To study the heat distribution that produces tissue coagulation, we used a thermographic camera aimed orthogonally to the laser beam axis to obtain thermal maps. Immediately after surgical resection, specimens of human stomach were irradiated near the resected edge, and the heat emitted sideways was detected by an infrared image system. A magnifying lens mounted on the camera enabled us to obtain 0.1 mm spatial resolution of the isothermic curves. The thermal analysis showed that the maximum depth where the increase in temperature reached 25 degrees C (corresponding to a coagulation temperature of about 60 degrees C) was never greater than 3 mm, irrespective of the power and exposure time used. Moreover, the bidimensional thermal maps showed that the temperature did not decrease in a purely exponential fashion along the beam axis, but reached a maximum at about 1 mm beneath the surface. This fact, which confirms the decrepitation theorem, could explain the explosion inside the tissues observed in surgical application of the Nd:YAG laser.

Body Temperature↗

Hyperthermal effects in phototherapy with hematoporphyrin derivative sensitization.

Although the photochemical reaction of hematoporphyrin derivative (HpD) appears to play a major role in cytotoxic activity, the hyperthermal contribution to tumor destruction has not yet been clarified. We investigated its role in the effectiveness of laser photoradiation therapy using MS-2 sarcoma transplanted into the hind pad of BALB/c mice as the experimental model. Mice received HpD i.v., 25 mg/kg - 24 h before exposure to light delivered from a dye laser or Nd-YAG laser, or before warming in a thermostated bath. Since our aim was not to cure the tumor, the treatment response was evaluated only as inhibition of tumor growth at different days after treatment. Our results support the view that in laser photochemotherapy the hyperthermia produced by irradiation and the photodynamic effect mediated by HpD could contribute to tumor destruction. Moreover, a synergistic interaction between the photodynamic effect and heat was observed in this experimental model.

Animals↗

Laser phototherapy following HpD administration in superficial neoplastic lesions.

We report our preliminary clinical experience with hematoporphyrin derivative (HpD) injection and argon or dye laser irradiation for the treatment of 61 surface neoplastic lesions in 7 patients. Forty-three sites were multiple basal cell carcinoma in 5 patients, and the remaining 18 were cutaneous and subcutaneous recurrent breast carcinoma after mastectomy in the thoracic wall. The patients were selected on the basis of the lack of indication for conventional therapeutic modalities. The selection of irradiation procedures and laser source was based on the thickness of the lesion and extension of the disease. The photochemical reaction between HpD injected i.v. at a dose of 3 mg/kg body weight and the laser beam at a dose of 60 to 120 J/cm2 resulted in 75% favorable responses at the treated sites. Optimal therapeutic effects appeared to be critically dependent on total light dose and tumor infiltration patterns. The phototherapeutic technique proved to be effective in selected cases of neoplastic lesions, especially when conventional treatment modalities were poorly indicated or contraindicated.

Aged↗

A comparison of efficacy of photoradiation therapy and other conventional treatment modalities on experimental MS-2 sarcoma.

The therapeutic efficacy of photoradiation therapy (PRT) following hematoporphyrin derivative (HpD) administration was compared in the experimental MS-2 tumour model to that of conventional treatment methods for local control of neoplastic diseases. The therapeutic effects of PRT and surgical removal of primary tumour were comparable in these experiments. However, optimal effects were critically dependent on the stage of tumour development. In addition, the therapeutic advantage of PRT over radiotherapy suggest an interesting role of a new approach in tumours resistant to this conventional treatment.

Animals↗

Effectiveness of laser photoradiation therapy following hematoporphyrin derivative administration in the experimental MS-2 tumor model.

The effectiveness of laser photoradiation therapy with hematoporphyrin derivative sensitization was tested in the MS-2 sarcoma. This solid tumor, transplanted into the pad of the hind leg of BALB/c mice, was found to be a sensitive experimental model for a quantitative evaluation of response to phototherapy and for determination of critical parameters in laser phototherapy treatment. Under our experimental conditions, optimal therapeutic effects appeared to be critically dependent on drug dose, number of treatments, light intensity, and irradiation of the peripheral border of the tumor.

Animals↗

The outpatient-procedure effectiveness of laser treatments in oncology.

The outpatient procedure of CO2 laser surgery has been recently integrated into the routine activity of the National Cancer Institute, Milan. Specific operative protocols that are codified for laser outpatient selection after adequate staging by pathology are presented. Specific indications for gynecologic disease (preneoplastic disorders, CIN, VAIN, and VIN), and general-surgery neoplastic disorders (soft tissue sarcomas, lip and oral cavity lesions, breast lesions) are described. Details of the safety procedures, rules of application, laser instrumentation accessories and wattages, both with vaporization and excisional technique, are reported. An overall rate of 30% out of the 4,000 cases treated yearly are selected for laser treatment procedures on the basis of the evaluation of real advantages. The general advantages of laser surgical applications such as reduction of bleeding and postoperative pain, early and late complications; no-touch method; and patient acceptability--have been emphasized in the routine outpatient procedures. Reduction of the total costs and of the waiting list for hospitalization by the new procedures are finally considered.

Ambulatory Surgical Procedures↗

CO2 lasers: beam patterns in relation to surgical use.

According to surgeons operating with a variety of CO2 lasers available at the National Cancer Institute of Milan (Coherent, Sharplan, Valfivre), these lasers have different cutting and coagulation properties. To identify what physical parameters might corroborate the subjective impression of the surgeons, a comparative study of the crater forms in perspex samples was performed. Perspex was chosen for its thermal properties (in fact, its thermal conductivity and diffusivity are similar to those of organic tissue) and because it allowed good visualization and measurement of crater characteristics. Depth of penetration, crater diameter, and extension of thermal damage were measured against power, focal length, and exposure time for each CO2 laser model. These results can be used as an index of behaviour of different surgical lasers. It appears that for fully characterizing the interaction of surgical lasers with the sample, it is necessary to specify either power, focal length, exposure time, or beam mode.

Biophysical Phenomena↗

Laser oncology in Italy: experimental research and clinical applications at the National Cancer Institute, Milan.

CO2, Nd:YAG, and argon lasers have been used for 5 years for experimental and clinical procedures at the National Cancer Institute of Milan under the auspices of the National Research Council. Experimental data regarding tumor cell spread through lymphatic and hematic channels and cell viability in the fumes after CO2 laser irradiation are reported. New advantages in the combined treatment modalities have been demonstrated, since the synergism between the low power argon laser beam and chemotherapeutic agents (anthracyclines) was assessed on cell cultures and the least toxic and the most effective doses of the drugs were identified. Due to the optical properties of the laser beam, physical measurements of the delivered energy and mathematical calculation of the energy per tissue volume unit to be ablated increase the precision in microsurgery especially when conservative managements are indicated. Main applications in surgical oncology, and comparison versus conventional methods, both with vaporization and excisional techniques, according to specific therapeutic protocols, in general surgery, otolaryngology, gynecology, and endoscopy, even on an outpatient basis, are finally illustrated in a series of 600 cases.

Animals↗