Sensor-controlled scalp cooling to prevent chemotherapy-induced alopecia in female cancer patients.

BACKGROUND: Scalp cooling has been used since the 1970s to prevent chemotherapy-induced alopecia, one of the most common and psychologically troubling side effects of chemotherapy. Currently available scalp cooling systems demonstrate varying results in terms of effectiveness and tolerability. METHODS: For the present prospective study, 55 women receiving neoadjuvant, adjuvant, or palliative chemotherapy were enrolled. The aim was to assess the effectiveness of a sensor-controlled scalp cooling system (DigniCap: Sysmex Europe GmbH, Norderstedt, Germany) to prevent chemotherapy-induced alopecia in breast or gynecologic cancer patients receiving 1 of 7 regimens. Clinical assessments, satisfaction questionnaires, and alopecia evaluations [World Health Organization (who) grading for toxicity] were completed at baseline, at each cycle, and at completion of chemotherapy. RESULTS: Of the 55 patients, 78% underwent scalp cooling until completion of chemotherapy. In multivariate analysis, younger women and those receiving paclitaxel weekly or paclitaxel-carboplatin experienced less alopecia. The compound successful outcome ("no head covering" plus "who grade 0/1") was observed in all patients 50 years of age and younger receiving 4 cycles of docetaxel-cyclophosphamide or 6 cycles of paclitaxel-carboplatin. Conversely, alopecia was experienced by all women receiving triplet polychemotherapy (6 cycles of docetaxel-doxorubicin-cyclophosphamide). For women receiving sequential polychemotherapy regimens (3 cycles of fluorouracil-epirubicin-cyclophosphamide followed by 3 cycles of docetaxel or 4 cycles of doxorubicin-cyclophosphamide followed by 4 cycles of docetaxel), the subgroup 50 years of age and younger experienced a 43% success rate compared with a 10% rate for the subgroup pf older women receiving the same regimens. CONCLUSIONS: The ability of scalp cooling to prevent chemotherapy-induced alopecia varies with the chemotherapy regimen and the age of the patient. Use of a compound endpoint with subjective and objective measures provides insightful and practical information when counselling patients.

PEG-m-THPC-mediated photodynamic effects on normal rat tissues.

Photodynamic therapy (PDT) of malignancies uses light to activate a photosensitizer preferentially accumulated in cancer cells. The first pegylated photosensitizer, tetrakis-(m-methoxypolyethylene glycol) derivative of 7,8-dihydro-5,10,15,20-tetrakis(3-hydroxyphenyl)-21-23-[H]-porphyrin (PEG-m-THPC), was evaluated in non-tumor-bearing rats. The aim of this study was to assess the photodynamic threshold for damage and its sequelae in normal rat tissue. Thirty-five Fischer rats were sensitized with 3, 9 or 30 mg/kg body weight PEG-m-THPC. Colon, vagina and perineum were irradiated with laser light of 652 nm wavelength and an optical dose of 50, 150 or 450 J/cm fiber length. Temperature in the pelvis was measured during PDT. Three days following PDT the effect on skin, vagina, colon, striated muscle, connective tissue, nerves and blood vessels was assessed by histology. The healing of the above-mentioned tissues was assessed on two rats 3 and 8 weeks after PDT using 9 mg/kg PEG-m-THPC activated with 450 J/cm laser light. No dark toxicity was observed. PDT using 30 mg/kg PEG-m-THPC induced severe necrosis irrespective of the optical dose. Body weight of 9 or 3 mg/kg activated with less than 450 J/cm induced moderate or no damage. No substantial increase in body temperature was seen during PDT. Tissues with severe PDT-induced damage seem to have a good tendency to regenerate. We conclude that within the dose required for tumor treatment PEG-m-THPC is a safe photosensitizer with promising properties. PDT of the colon mucosa below 9 mg/kg PEG-m-THPC and 150 J/cm seems to be safe. All other tissues can be exposed to 9 mg/kg PEG-m-THPC activated with less than 450 J/cm laser light with little side effects.

Highly selective targeting of ovarian cancer with the photosensitizer PEG-m-THPC in a rat model.

Photodynamic therapy (PDT) uses light to activate a photosensitizer that has been absorbed or retained preferentially by cancer cells after systemic administration. The first pegylated photosensitizer, tetrakis-(m-methoxypolyethylene glycol) derivative of 7,8-dihydro-5,10,15,20-tetrakis(3-hydroxyphenyl)-21,23-[H]-porphyrin (PEG-m-THPC), was evaluated to target selectively unresectable pelvic ovarian cancer bulks. Our goals were two-fold: (1) to establish an ovarian cancer model suitable for the development of debulking techniques and (2) to characterize the pharmacokinetics and tumor selectivity of PEG-m-THPC by fluorescence microscopy. NuTu-19 ovarian cancer cells were injected into the caudal part of the right psoas muscle of Fisher rats. Five weeks later, 30 mg/kg body weight of PEG-m-THPC was injected intravenously. Necropsy was performed between 4 and 10 days following drug application, and fluorescence of the tumor and various abdominal organs was measured. All rats developed bulky pelvic tumors with an average diameter of 2.6 cm (+/- 0.6 SD). Tumor masses were encompassing and infiltrating pelvic organs in a similar manner to ovarian cancers in humans. Fluorescence of cancer tissue was maximal 8-10 days following drug application. At 8 days, the tumor-to-tissue ratio was 40:1 (+/- 12 SE) for most abdominal organs. We conclude that this tumor model may be used for the study of new pelvic debulking techniques, and that the tumor selectivity of PEG-m-THPC is exceptionally high 8 days after drug application. Based on these data, we are currently developing a PDT-based minimally invasive debulking technique for advanced ovarian cancer.

ErbB-2 expression does not predict in vitro CMF-chemosensitivity of primary breast tumors.

The predictive value of the oncogene product ErbB-2 for chemosensitivity of tumors is still unclear. We therefore correlated the in vitro chemosensitivity of breast cancer specimens from 125 patients with the respective expression levels of ErbB-2. Twenty-six percent of the patients were premenopausal. Chemosensitivity was tested with the adenosine triphosphate cell viability assay and ErbB-2 content was assessed in the same specimens by ELISA. With the cut-off value used 34% of the patients had tumors with positive ErbB-2 levels. The mean ErbB-2 amount of positive tumors was 388 U/mg +/- 254 and of negative tumors 65 U/mg +/- 36. The mean survival fractions (SF) in the chemosensitivity assay at 0.25 peak plasma concentration (PPC) of a combination of cyclophosphamide, methotrexate and 5-fluorouracil (CMF) were not significantly different for ErbB-2-positive and for ErbB-2-negative tumors (0.68 and 0.65, respectively (p = 0.6)). The median SF for positive tumors was 0.68 and for negative tumors 0.62, respectively. Similarly, at four times the PPC of CMF no significant differences in SF of ErbB-2-positive and -negative specimens were found (p = 0.8). Comparison of the median of ErbB-2-protein content of CMF-sensitive tumors with that of CMF-resistant tumors also yielded no significant difference. Taken together, no significant association between in vitro CMF-chemosensitivity and expression levels of ErbB-2 in tumors of patients with primary chemotherapy naive breast cancer could be determined.

A mathematical model for light dosimetry in photodynamic destruction of human endometrium.

We are involved in the development of photodynamic therapy (PDT) as a minimally invasive method for treating dysfunctional uterine bleeding, one of the primary clinical indications for hysterectomy. In this paper, we analyse light propagation through the uterus in order to specify the requirements for a light delivery system capable of effectively performing endometrial PDT. Our approach involves developing an analytical model based on diffusion theory to predict optical fluence rate distributions when cylindrical and spherical optical applicators are placed in the uterine cavity. We apply the results of our model calculations to estimate the thermal effects of optical irradiation and the effective photodynamic optical dose. Theoretical fluence rate calculations are compared to fluence rate measurements made in fresh, surgically removed human uteri. Our results show that a trifurcated cylindrical optical applicator inserted into the human uterus can provide a light dose that is sufficient to cause photodynamic destruction of the entire endometrium. When the optical power per unit length of each cylindrical applicator is 100 mW cm-1 (at 630 nm), a fluence rate of 40 mW cm-2 is delivered to the boundary layer between the endometrium and the myometrium (a depth of about 4-6 mm). The optical fluence delivered to the boundary layer after 20 min of exposure is 50 J cm-2, a level that is generally accepted to cause tissue damage throughout the endometrium in most patients.

[Chemotherapy of endometrial cancer revisited]. / Stellenwert der Chemotherapie in der Behandlung des Endometriumkarzinoms.

The current status and future directions of chemotherapy in the management of endometrial cancer are reviewed. For patients with advanced or recurrent endometrial carcinoma the most active single drugs are doxorubicin, epirubicin, cisplatin, carboplatin, paclitaxel, ifosfamide, 5-fluorouracil and vincristine with response rates ranging from 18 to 36%. Data at the present time support the conclusion that if chemotherapy is indicated a combination of doxorubicin + cisplatin is the standard chemotherapy for patients with advanced or recurrent endometrial carcinoma and yields a response rate of 47-60%. A first trial using a combination of these drugs with paclitaxel promises an increase in response rate to 73%, but data regarding prolongation of survival are not yet available. Up to now the benefit of neither chemotherapy nor endocrine therapy could be established in the adjuvant setting.

[Stereotaxic breast biopsy techniques have become the standard of care for mammographically suspicious lesions]. / Stellenwert der modernen stereotaktischen Biopsiemethoden bei mammographisch suspekten Läsionen.

An optimal technique for the evaluation of nonpalpable, suspicious mammographic lesions should have a low technical failure rate, no false-negative results and should remove the lesion completely. Since most of these lesions are benign, the procedure should be carried out in an outpatient setting without general anesthesia. Cancer is missed in 2.6% of cases with excisional biopsy following needle localization. Furthermore, 50-83% of these patients undergo a second surgical intervention for definitive surgical treatment. In contrast, the rate of missed cancers is less than 0.7% following stereotaxic core or large-core biopsies. However, using these techniques, discordant results and histologic high-risk lesions need to be recognized and reexcized. The cost-effectiveness of stereotaxic vacuum-assisted core biopsy has been demonstrated. Stereotaxic breast biopsy techniques such as vacuum-assisted core biopsy and large-core biopsy for suspicious mammographic lesions have low false-negative rates and result in few histologic underestimations.

Cost-effectiveness of trastuzumab in the adjuvant treatment of early breast cancer: a model-based analysis of the HERA and FinHer trial.

BACKGROUND: Routine adjuvant administration of trastuzumab (T) has been implemented in most centers, but its economic impact has not yet been well examined. METHODS: A Markov model was constructed based on clinical data of the Herceptin Adjuvant (HERA) and the Finland Herceptin (FinHer) trials. Costs from the perspective of a Swiss health care provider were calculated based on resource use. RESULTS: On the basis of HERA data, our model yielded an overall survival rate of 71.8% for the T group versus 62.8% for the control group [risk ratio (RR) = 0.87) after 10 years and 62.9% versus 52.7% (RR = 0.84) after 15 years. Cost-effectiveness resulted in 40505 Euros (EUR) per life years gained (LYG) after 10 years and 19673 EUR per LYG after 15 years. For the FinHer regimen, overall survival after 10 and 15 years resulted in 81.8% versus 66.1% (RR = 0.81) and 73.6% versus 57.0% (RR = 0.77). Costs of 8497 EUR per patient could be saved after 10 years and 9256 EUR after 15 years compared with the control group. CONCLUSION: In a long-term perspective, adjuvant T based on the HERA regimen can be considered cost-effective. The regimen used in the FinHer trial is even cost saving, but estimations are based on a single small trial.

Photodynamic therapy of vulvar intraepithelial neoplasia III using topically applied 5-aminolevulinic acid.

OBJECTIVES: The aim of this study was twofold: first, to determine the feasibility of photodynamic therapy (PDT) of vulvar intraepithelial neoplasia III (VIN III) using topically applied 5-aminolevulinic acid (ALA) for photosensitization, and second, to compare PDT results with those of laser evaporation and local excision. METHODS: Fifteen patients with VIN III had 10 g of 10% ALA gel applied to the entire vulva. Two to three hours after drug application the vulva was irradiated with 120 J/cm(2) laser light at a wavelength of 635 nm. The procedure was performed without anesthesia in most patients. Thirty patients with VIN III treated by laser evaporation and 27 patients treated by surgical excision served as controls. RESULTS: Eight weeks following PDT, 11 of 15 patients were free of VIN III as determined by biopsy. Excellent tissue preservation was achieved and no ulcers or scarring occurred. Three recurrences were seen during follow-up, at 5, 6, and 7 months after PDT. Twelve months after treatment, analysis of disease-free survival revealed no statistically significant difference between patients treated with PDT and patients treated with conventional treatment modalities (P = 0.67) but the power of this analysis is low. In multivariate analysis, multifocal disease was the sole variable associated with a reduced disease-free survival. CONCLUSION: While PDT of VIN III seems to show efficacy similar to that of conventional treatment modalities it offers unique advantages: healing time is short, preservation of normal vulvar appearance is excellent, and PDT may be performed without anesthesia. Hence, PDT of VIN III deserves further investigation.

[Surgical laparoscopy in tumors of the adnexa]. / Operative Laparoskopie bei Adnextumoren.

OBJECTIVES: The laparoscopic management of adnexal masses is still controversial. The main problems are preoperative diagnosis, operative technique and the possibility of compromising the prognosis by spillage of cancer cells when operating on a hitherto unrecognized early stage ovarian cancer. We report on our experience with minimal invasive surgery of adnexal masses. METHOD: From June 1989 to July 1992, 375 patients underwent surgery for adnexal tumors at the University Hospital, Zurich. In 112 cases a laparoscopic operation was performed. The indications were unilateral or bilateral masses in the adnexal region with or without clinical symptoms. The preoperative workup included patient's history, clinical examinations, vaginal sonography and intraoperative evaluation of the tumor. RESULTS: In 72% (83) of cases the organs were preserved by the laparoscopic procedure while in 28% (32) salpingo-oophorectomy, ovariectomy or salpingectomy was performed. The histopathologic findings included cystadenomas, cystadenofibromas, benign cystic teratomas, simple and functional cysts, mesothelium cysts, tubo-ovarian abscesses, endometriomas, and torqued tubes and/or ovaries. In no patient was a malignant process found. Only one postoperative complication was noted in a patient who had to be relaparoscoped due to adhesions to the operated ovary. One recurrence occurred in a hydrosalpinx. CONCLUSIONS: Adnexal masses may safely be managed laparoscopically, with all the advantages of minimal invasive surgery, provided that strict diagnostic and therapeutic rules are observed.

Selective photosensitizer localization in the human endometrium after intrauterine application of 5-aminolevulinic acid.

OBJECTIVE: Our purpose was twofold: to determine the distribution of the endogenous photosensitizer protoporphyrin IX in the uterus and to ascertain the time interval leading to maximal endometrial fluorescence after intrauterine instillation of 5-aminolevulinic acid. STUDY DESIGN: One milliliter of a 400 mg/ml 5-aminolevulinic acid-Hyskon solution was instilled into the uterine cavity of 27 women before hysterectomy. On frozen sections of uterine samples 5-aminolevulinic acid-induced fluorescence was measured with fluorescence microscopy. RESULTS: 5-Aminolevulinic acid-induced fluorescence could first be detected in the superficial endometrial glands 75 minutes after drug injection. In the endometrial gland stumps fluorescence intensity peaked 4 to 8 hours after 5-aminolevulinic acid instillation and was > 48 times higher than in the underlying myometrium. CONCLUSIONS: Fluorescence in the endometrial glands suggests that selective photodynamic destruction of the endometrium may be possible 4 to 8 hours after intrauterine 5-aminolevulinic acid instillation.

[Multivariate analysis of clinico-pathologic predictors of axillary lymph node metastasis in invasive breast carcinoma]. / Multivariate Analyse klinisch-pathologischer Prädiktoren der axillären Lymphknotenmetastasierung beim invasiven Mammakarzinom.

UNLABELLED: The aim of this study was to find both predictors of axillary lymph node involvement and predictors of level II or III involvement. With these predictors patients should be selected who can be spared axillary lymph node dissection or who qualify for removal of only first-level lymph nodes. 239 consecutive patients with invasive breast cancer stage I-III treated with total axillary dissection were evaluated. In multiple logistic regression analysis 17 clinical and histopathological variables were included. We found 4 multivariate significant predictors for metastatic axillary involvement: Clinically positive axilla, peritumoural lymphatic vessel invasion, multicentric or multifocal tumours and a large number of past pregnancies. Multivariate significant predictors of involvement of level II or III were peritumoural lymphatic vessel invasion, younger age, larger tumour size, multicentric or multifocal tumours and postmenopausal patient. The metastatic involvement of more than 3 nodes was associated with young age and clinically positive axilla. With these easily available predictors a reliable assessment of risk of metastatic involvement of the upper levels of the axillary nodes could be defined. The binary logistic regression model to axillary node involvement had a rather unsatisfactory predictive value. CONCLUSIONS: The risk calculation of level II or III involvement with these predictors may help the surgeon to find the adequate extent of axillary clearance needed in the individual patient. Multiparity proved to be an independent predictor of metastatic axillary node involvement.

Uptake of the photosensitizer benzoporphyrin derivative in human endometrium after topical application in vivo.

STUDY OBJECTIVE: To determine both the time leading to maximum endometrial drug uptake and distribution of the photosensitizer benzoporphyrin derivative-monoacid ring A (BPD-MA) after intrauterine instillation (Canadian Task Force classification ). DESIGN: Assessment of histology specimens (Canadian Task Force classification I). SETTING: University-based facility. PATIENTS: Twenty-two women scheduled for hysterectomy. INTERVENTIONS: We instilled 1.5 ml of a 2 mg/ml of BPD-MA-Hyskon solution into the uterine cavity of 22 women before hysterectomy. The fluorescence induced was measured by fluorescence microscopy on frozen sections of uterine samples from 20 of 22 patients. Systemic uptake of BPD-MA was determined in plasma of six patients by spectrofluorometry. MEASUREMENTS AND MAIN RESULTS: The BPD-MA-induced fluorescence was maximum 1 hour after instillation, with significantly higher uptake in endometrial glands than in underlying stroma. Hormonal endometrial stimulation correlated with fluorescence intensity: atrophy < secretory phase < proliferative phase. Strongest fluorescence was seen in endometrial cancer. Drug uptake by endometrial glands was found at a depth of 2 mm from the surface. Systemic uptake of BPD-MA was under the detection level of 2 ng/ml after application. CONCLUSION: Fluorescence in human endometrial glands suggests that selective destruction of human endometrium with photodynamic therapy may be possible 1 hour after topical application of BPD-MA for benign and malignant lesions. No systemic drug uptake, side effects, or major technical difficulties were detected. Limited penetration of the drug and selective uptake by endometrial glands provided a high degree of safety for endometrial ablation.

Photodynamic therapy of DNA mismatch repair-deficient and -proficient tumour cells.

Loss of DNA mismatch repair is a common finding in hereditary nonpolyposis colon cancer as well as in many types of sporadic human tumours. DNA mismatch repair-deficient cells have been reported to be resistant to many chemotherapeutic agents and to radiotherapy, and to have the potential of rapidly acquiring additional mutations leading to tumour progression. Photodynamic therapy is a new treatment modality using light to activate a photosensitiser that preferentially localises in tumour cells. An oxygen dependent photochemical reaction ensues, resulting in selective tumour necrosis. The effect of loss of DNA mismatch repair activity on the sensitivity to photodynamic therapy was tested using pairs of cell lines proficient or deficient in mismatch repair due to loss of either MLH1 or MSH2 protein function. Cells were incubated with the photosensitiser 5,10,15,20-meta-tetra(hydroxyphenyl)chlorin and exposed to laser light at 652 nm with various optical doses ranging from 0-1 J cm(-2). Cell survival was assessed using the clonogenic assay. Loss of MLH1 or MSH2 function was not associated with resistance to photodynamic therapy. MCF-7 cells repeatedly treated with photodynamic therapy expressed parental levels of MLH1, MSH2, MSH6, and PMS2. DNA mismatch repair-deficient and -proficient cells showed similar subcellular distributions of meta-tetra(hydroxyphenyl)chlorin as analysed by laser scanning and fluorescence microscopy. Therefore, repeated exposure of tumour cells to photodynamic therapy does not seem to result in loss of DNA mismatch repair, and loss of mismatch repair, in turn, does not seem to contribute to resistance to photodynamic therapy. Our results suggest recommending photodynamic therapy as a strategy for circumventing resistance due to loss of DNA mismatch repair.

Structural and functional effects of endometrial photodynamic therapy in a rat model.

OBJECTIVE: Our purpose was to determine the optical dose required for irreversible endometrial destruction and prevention of implantation by photodynamic therapy with topical 5-aminolevulinic acid. STUDY DESIGN: Three hours after drug application 74 female Sprague-Dawley rats received varying doses of 630 nm of light delivered by an intrauterine cylindric diffusing fiber. RESULTS: A 64 J/cm2 in situ optical dose resulted in long-term irreversible endometrial destruction; 43 J/cm2 damaged endometrial stroma and myometrium but not glandular epithelium 1 day after photodynamic therapy. At this lower light dose endometrium regenerated to full thickness within 3 weeks; however, implantation sacs were significantly reduced. CONCLUSIONS: Photodynamic destruction of glandular epithelium accompanies irreversible endometrial ablation, whereas isolated stromal damage leads to reproductive impairment only. The optical dose required for endometrial ablation is approximately 1.5-fold higher than for reproductive impairment (functional damage) because of differential cell photosensitivity.

Minimally-invasive debulking of ovarian cancer in the rat pelvis by means of photodynamic therapy using the pegylated photosensitizer PEG-m-THPC.

Interstitial photodynamic therapy (PDT) using the pegylated photosensitizer PEG-m-THPC was evaluated as a minimally-invasive procedure to selectively debulk unrespectable pelvic ovarian cancer (NuTu-19) in immunocompetent rats. To assess tumour selectivity, PEG-m-THPC at dosages of 0.3, 3.0 and 30 mg kg(-1) body weight was administered intravenously to 30 rats 4 weeks following tumour induction. Eight days later laser light at 652 nm and optical doses ranging from 100 to 900 J cm(-1) diffuser-length was delivered by an interstitial cylindrical diffusing fibre inserted blindly into the pelvis. Three days following light application, the volume of necrosis was measured and the damage to pelvic organs was assessed histologically on cross sections. For analysis of survival, 20 tumour-bearing rats received PDT using drug doses of 3 or 9 mg kg(-1) body weight and an optical dose of 900 J cm(-1) diffuser-length, whereas ten untreated tumour-bearing rats served as controls. The histological assessment of PDT induced necrosis showed a non-linear dose-response for both the photosensitizer dose and the optical dose. The lowest drug dose activated with the highest optical dose did not induce more necrosis than seen in tumour-bearing control animals. The same optical dose induced necrosis of 17 mm in diameter using 30 mg kg(-1) and 11 mm using 3 mg kg(-1) photosensitizer. The optical threshold for induction of significant necrosis was between 100 and 300 J cm(-1) diffuser-length for 30 mg kg(-1) and between 300 and 500 J cm(-1) for 3 mg kg(-1) PEG-m-THPC. Significant damage to normal pelvic organs was only seen if 30 mg kg(-1) photosensitizer was activated with optical doses of 700 J cm(-1) or more. In the survival study, all treated animals survived PDT for at least 2 weeks and the intestinal and urinary tract remained functional. No clinical signs of blood vessel or nerve injury were observed. Mean overall survival of untreated tumour-bearing rats was 25.0 +/- 4.5 days compared to 38.4 +/- 3.8 days and 40.0 +/- 3.6 days for rats treated with 3 mg kg(-1) or 9 mg kg(-1) PEG-m-THPC mediated PDT respectively (P < 0.05). We conclude that PEG-m-THPC mediated PDT has a favourable therapeutic window and that this minimally-invasive procedure can reduce pelvic cancer bulks effectively and selectively.

Intrauterine light delivery for photodynamic therapy of the human endometrium.

Photodynamic therapy is currently being evaluated as a minimally invasive procedure for endometrial ablation not requiring anaesthesia. Light penetration depths at 630, 660 and 690 nm and the optimal configuration of intrauterine light-diffusing fibres were determined in 14 human uteri to assist in the design of a light intrauterine device. Post-menopausal ex-vivo uteri showed a significantly lower light penetration depth than pre-menopausal uteri. With a single central diffusing fibre inserted, the fluence rate measured in the uterine wall at the most remote point of the cavity decreased to 1.1 +/- 0.4% of that measured at closest proximity, whereas it decreased to only 40.0 +/- 9.0% with three fibres. Distension of the uterine cavity with 2 ml of an optically clear fluid increased the fluence rate at the fundus between the fibres at a depth of 2 mm by a factor of 4. We conclude that in normal-sized pre-menopausal uterine cavities, three diffusing fibres will deliver an optical dose above the photodynamic threshold level at a depth of 4 mm, even in the most remote areas, in < 30 min without causing thermal damage. For distorted and elongated cavities, either slight distension of the cavity or the insertion of a fourth diffusing fibre is required.

Selective photosensitizer distribution in vulvar condyloma acuminatum after topical application of 5-aminolevulinic acid.

OBJECTIVE: Our purpose was to determine the feasibility of selective photosensitization of vulvar condylomas by use of tropical application of 5-aminolevulinic acid. STUDY DESIGN: In vivo fluorescence was assessed and biopsy specimens of condylomas were taken for fluorescence microscopy in 24 patients at different times after application of 2.5% 5-aminolevulinic acid ointment or 20% 5-aminolevulinic acid cream. RESULTS: Both in vivo fluorescence imaging and fluorescence microscopy showed selective fluorescence of condylomas of the labia minora and vestibule only within short time intervals, because fluorescence of poorly keratinized normal epithelium was induced by both 5-aminolevulinic acid formulations. In non-hair-bearing skin, lesional fluorescence remained highly selective. Fluorescence microscopy showed that 90 minutes after drug application peak selectivity in epithelial lesional fluorescence was significantly higher with 2.5% 5-aminolevulinic acid ointment (4.5 +/- 0.9) than it was with 20% cream (2.1 +/- 0.2). CONCLUSION: Selective fluorescence of vulvar condyloma acuminatum can be induced by nonselective topical 5-aminolevulinic acid application. Studies evaluating selective photodynamic destruction of condylomas are justified.