Daylight Photodynamic Therapy: An Update.

Daylight photodynamic therapy (dPDT) uses sunlight as a light source to treat superficial skin cancer. Using sunlight as a therapeutic device has been present for centuries, forming the basis of photodynamic therapy in the 20th century. Compared to conventional PDT, dPDT can be a less painful, more convenient and an effective alternative. The first clinical uses of dPDT on skin cancers began in Copenhagen in 2008. Currently, aminolevulinic acid-mediated dPDT has been approved to treat actinic keratosis patients in Europe. In this review article, we introduce the history and mechanism of dPDT and focus on the pros and cons of dPDT in treating superficial skin cancers. The future applications of dPDT on other skin diseases are expected to expand as conventional PDT evolves.

Photon irradiation using a water bath technique for treatment of confluent carcinoma in situ of the hand, digits, and nail bed: a case report.

BACKGROUND: Confluent squamous cell carcinoma in situ, or Bowen's disease, involving the hand, digit, and nail bed is rare and represents a significant therapeutic challenge. Surgical excision is recommended as first-line treatment but in cases of extensive disease can lead to unacceptable functional morbidity or cosmetic outcomes. Radiation therapy has been shown to be equally efficacious to surgery in the treatment of carcinoma in situ but its use has historically been limited due to concerns regarding toxicity. In this case report we present a novel therapeutic technique that may enable radiotherapy to be employed as a definitive treatment option in these challenging cases. CASE PRESENTATION: A 75-year-old white man with a previous history of carcinoma in situ of his right hand previously treated with 5-fluorouracil presented with recurrent biopsy-proven confluent squamous cell carcinoma in situ of multiple surfaces of his right hand and digits with involvement of nail beds. To avoid extensive resection and possible amputation he was offered definitive external beam radiation therapy utilizing a water bath as a tissue-equivalent bolus material. This protocol enabled improved dose homogeneity to the target volume while minimizing acute toxicity. He experienced complete clinical resolution of the disease with only minimal acute edema and hyperpigmentation. Twenty months following treatment completion he remains disease-free with normal function and excellent cosmesis. CONCLUSIONS: Therapeutic radiation utilizing water as a tissue-equivalent bolus in this complicated case enabled definitive treatment of disease without compromising functional or cosmetic outcomes. Radiotherapy may therefore be an alternative and under-utilized approach to surgical excision in difficult-to-treat cases of carcinoma in situ.

Tratamiento de la enfermedad de Bowen con terapia fotodinámica y ventajas de la aplicación secuencial de imiquimod tópico / Treatment of Bowen disease with photodynamic therapy and the advantages of sequential topical imiquimod

La terapia fotodinámica (TFD) ha demostrado ser un tratamiento útil y eficaz en queratosis actínicas, enfermedad de Bowen (EB) y carcinoma basocelular. Presentamos una serie de 13 lesiones de EB tratados con TFD. A los 3 meses del tratamiento 11/13 (84%) lesiones presentaron respuesta completa. A los 18 meses la respuesta completa fue de 9/13 (70%) lesiones. Los pacientes que presentaron respuesta parcial o recidiva fueron tratados con imiquimod tópico al 5%, con la consiguiente respuesta completa. Las lesiones con respuesta parcial o recidiva fueron las de mayor tamaño: entre 3 y 5cm de diámetro. La TFD en monoterapia o combinada secuencialmente con imiquimod es una excelente opción terapéutica para la EB, bien tolerada, con mínimos efectos secundarios y unos resultados satisfactorios, y sobre todo indicada en lesiones de gran tamaño, múltiples, en áreas de difícil reconstrucción quirúrgica o en pacientes ancianos con riesgo quirúrgico elevado

Photodynamic therapy (PDT) has been shown to be useful and effective in the treatment of actinic keratosis, Bowen disease, and basal cell carcinoma. We present a series of 13 Bowen disease lesions treated using PDT. Complete responses were achieved in 11 (84%) of the lesions after 3 months of treatment; at 18 months, complete responses were seen in 9 (70%) of the lesions. Patients who presented a partial response or recurrence were treated with topical 5% imiquimod and achieved complete responses. The lesions that presented partial response or recurrence were the largest lesions, between 3 and 5cm in diameter. PDT in monotherapy or combined sequentially with imiquimod is an excellent and well-tolerated therapeutic option for Bowen disease. The treatment has few adverse effects and shows satisfactory results, particularly in multiple large lesions in areas of difficult surgical reconstruction or in elderly patients with a high surgical risk

Multiple-digit periungual Bowen's disease: a novel treatment approach with radiotherapy.

Multiple periungual Bowen disease [BD; also known as squamous cell carcinoma (SCC) in situ] is rare. The pathogenesis of the disease is linked to human papilloma virus, and in some instances to chronic immunosuppression. The usual management of periungual BD is by local excision, Mohs micrographic surgery or distal phalanx amputation. Our patient was offered radiotherapy in the hope of maximizing residual function and minimizing morbidity from treatment. A good response was seen at 2 months post-radiotherapy, but this was followed by relapses at 4 and 6 months post-radiotherapy. Persistent anonychia resulted in improved access to the involved skin, making topical therapy possible. Radiotherapy can be a valuable management approach for periungual SCC/BD in locations where amputation could result in substantial disability.

The potential role of radiation therapy in Bowen's disease: a review of the current literature.

BACKGROUND: Bowen's disease is a form of squamous cell carcinoma in situ that can be transformed into invasive squamous cell carcinoma and should be treated according to its anatomical position. The aim of this article is to offer an overview of treatment options with an emphasis on radiation therapy in the treatment of Bowen's disease. METHODS AND MATERIALS: We performed overview of the literature based on database searches in PubMed/MEDLINE and we included articles till December 2010. Only papers published in English were included. RESULTS: There was no standard fractionation regimen: some physicians prescribed high doses, such as the ones of invasive skin cancer, whereas others prescribed lower doses because of the noninvasive nature of the disease, the sensitive anatomic location (e.g., extremity) and the large treatment area. Various studies demonstrate high rates of tumor control with minimal morbidity following definitive radiation therapy in the treatment of Bowen's Disease. Through a multidisciplinary assessment, the treatment of Bowen's disease can be individualized to optimize patient care. CONCLUSIONS: Radiation therapy is an effective treatment option for Bowen's disease of the skin. Local recurrences seem to be equally low in patients treated with high- and low-dose regimens. Radiotherapy preserves normal tissues ensuring a superior esthetic and functional outcome.

Effects of ultraviolet radiation exposure on FOXP3+ infiltration in cutaneous squamous cell carcinoma and basal cell carcinoma.

PURPOSE: To analyze the prevalence and significance of FOXP3+ infiltration into (pre)malignant skin carcinomas following ultraviolet radiation (UVR) exposure. The possible pathways that UVR impacts on FOXP3 are to be discussed. BACKGROUND: FOXP3+ regulatory T cells (FOXP3+ Tregs) are correlated to cutaneous squamous tumor progression. However, there is no information describing the prevalence of FOXP3+ infiltration in cutaneous premalignant and malignant squamous carcinomas with UVR exposure. METHODS: We investigated the prevalence of FOXP3+ infiltration in 14 patients with Bowen's disease, 40 squamous cell carcinoma SCC patients and 21 patients with basal cell carcinoma (BCC) by immunohistochemistry. RESULTS: The percentages of FOXP3+ vs. total peri-neoplasm infiltration cells (FOXP3+ PCT) were significantly higher in Bowen's disease and well-differentiated SCC that were exposed to UVR than these diseases not exposed to UVR (t = 3.5776, P = 0.0038; t' = 5.9214, P < 0.01, respectively). FOXP3+ PCT was also higher in less pigmented than pigmented sites in BCC (t = 3.369, P = 0.0032). CONCLUSIONS: This study shed some light on the effect of UVR on FOXP3+ infiltration in skin (pre)malignant carcinomas. Our data suggested that FOXP3+ infiltration was positively related to UVR exposure. The mechanisms merit further investigation.

Treatment efficiency of combining photodynamic therapy and ionizing radiation for Bowen's disease.

BACKGROUND: Topical 5-aminolevulinic acid photodynamic therapy (ALA-PDT) is widely used for treating Bowen's disease (BD), but recurrence and tumour cell persistence after ALA-PDT is sometimes problematic. Radiation therapy (RT) is also effective for BD, but is limited by its side-effects, such as refractory ulcers. OBJECTIVE: The objective of the study was to observe a synergic effect of combination therapy with ALA-PDT and RT for BD cases that did not respond effectively to prior ALA-PDT. METHODS: Subjects were BD patients whose lesion did not show complete remission or showed recurrence after prior ALA-PDT. A total of four cases involving four lesions were studied (three male and one female, mean age 69.5). ALA ointment (20%) was applied to the lesions. After 4 to 6h, subjects received combination therapy consisting of excimer-pumped dye laser radiation at 630nm (50J/cm(2) ) followed by electron-beam radiation (3Gy). The combination therapy was repeated every 2 to 3days for a total of four treatments. The lesions were evaluated clinically or histologically after the final combination therapy session. RESULTS: Following combination therapy, all of the lesions disappeared. Recurrence was not detected during the observations periods, which averaged 14.0months in duration. CONCLUSION: Our results indicate that the cure rate of BD could be improved by combination therapy with ALA-PDT and RT. Compared with conventional RT, the synergetic effect of this therapy might reduce the dose of radiation required, thereby also reducing skin side-effects such as refractory ulcers.

Conjunctival-corneal intraepithelial neoplasia (Bowen disease) treated with orthovoltage.

PURPOSE: To report an exceptionally large conjunctival-corneal intraepithelial neoplasia (CCIN) (Bowen disease), for which the size of the tumor made classical treatment difficult, and to highlight the role of orthovoltage as an alternative treatment mode with good results. METHODS: Observational case report of a healthy 61-year-old man with CCIN. Given its extension, alternative treatment was performed with orthovoltage, thus avoiding surgery, with adjuvant cryotherapy and mitomycin C, and potential complications. After administering topical anesthetic, a therapeutic contact lens was placed on the cornea; then, the eyelids were held open with a blepharostat. A 1-mm lead plate with a window was placed over the blepharostat. The shape of the window reproduced the shape of the tumor to protect the rest of the eye structures from radiation. Orthovoltage was administered with direct field radiation that was focused on the tumor through the window. The patient received 500 cGy in 2 sessions/week for 2 weeks (2000 cGy) and then 7 sessions 300 cGy daily (2100 cGy). RESULTS: Evolution was good without side effects. After one-year follow-up, the patient was asymptomatic, without alterations of ocular surface or deep structures. CONCLUSIONS: Safely administered orthovoltage may be a good therapeutic option for the treatment of CCIN when complete surgical resection is complicated by the extension of the tumor. Compared with topical treatment, radiation is easier to administer, shortens and simplifies the treatment, and is independent of patient compliance.

Complete remission after neoadjuvant chemoradiation in a stage IV vulvar cancer patient.

BACKGROUND: Surgery is the standard in the management of vulvar cancer. Several studies assessed the feasibility of radiochemotherapy as definitive therapy and/or neoadjuvant procedure in order to limit the extent of surgery. Combined radiochemotherapy is associated with considerable toxicity. The authors report on a modified neoadjuvant radiochemotherapy schedule which is isoeffective to the GOG (Gynecologic Oncology Group) protocol, but associated with less therapy-related toxicity. CASE REPORT: A 36-year-old woman with stage IV vulvar cancer and long-distance rectal infiltration is reported. Laparoscopic pretherapeutic staging confirmed pelvic and paraaortic lymph node metastases. RESULT: The patient received a neoadjuvant radiochemotherapy. After complete remission, a simple vulvectomy carried out 3 months later showed no evidence of tumor. Up to now, there is no evidence of tumor progression or recurrence. CONCLUSION: Preoperative conventionally fractionated simultaneous radiochemotherapy seems to be a feasible and safe treatment option for patients with locally advanced vulvar cancer in order to avoid exenterative surgery.

Radiotherapy using a water bath in the treatment of Bowen's disease of the digit.

PURPOSE: Bowen's disease (BD), a form of squamous cell carcinoma in situ, can transform into invasive squamous cell carcinoma and should be treated aggressively. Although standard treatment for BD is electrodessication and curettage, radiotherapy (RT) can be used for those patients who are poor surgical candidates or when surgery could result in a poor cosmetic and functional outcome. Surgical treatment of BD of the digit can result in poor function and sometimes amputation. Here, we report our experience using a unique water bath technique to treat BD of the digit. MATERIALS AND METHODS: This retrospective review evaluates the outcomes and toxicity of nine consecutive patients with BD of the digit treated with RT between 1999 and 2004. Fourteen digit lesions were immersed in a water bath and treated with photon irradiation. The median radiation dose delivered was 50Gy (range 25-66Gy) in 2.5Gy fractions (range 2-3Gy). RESULTS: The median age of the patients treated was 77 years (range 29-87 years). Three patients (33%) had more than one digit treated. With a median follow-up of 25 months (range 0.4-52 months), all 14 digit lesions are locally controlled. The majority of lesions demonstrated mild to moderate erythema, desquamation, or edema (grade 1-2) acutely following RT which resolved within one month of treatment. Two digits (14%) developed ulcers (grade 4) which healed following RT. The only long-term toxicity was decreased sensation and strength in one patient who had three circumferential lesions. This toxicity was limited and did not appear to influence the patient's daily activities (grade 2). CONCLUSIONS: These preliminary results demonstrate high rates of tumor control with minimal morbidity following definitive RT in the treatment of BD of the digit, and suggest that RT may be a viable treatment alternative to surgery for selected lesions. Through a multidisciplinary assessment, treatment of BD of the digit can be individualized to optimize patient care.

An extensive case of Bowen's disease in an HIV-positive male.

Bowen's disease is a form of squamous cell carcinoma in situ often associated with human papillomavirus (HPV). HPV has been hypothesized to cause in situ carcinoma via multiple mechanisms including cell immortalization and cell cycle disruption. Coinfection with HIV is associated with greater risk of malignancy. We describe a case of HPV-associated Bowen's disease in a 44-year-old African American male with sexually acquired HIV (CD4 < 20) who presented with an extensive skin lesion encompassing his penis, scrotum, and left inguinal canal.

Radiation therapy for Bowen's disease of the skin.

PURPOSE: To assess the clinical outcome in the radiation therapy (RT) of squamous carcinoma in situ of the skin (Bowen's disease). We focused on the local control rate and the toxicity according to the biologically effective dose (BED). METHODS AND MATERIALS: A retrospective review was performed on 44 patients with Bowen's disease treated at Princess Margaret Hospital from April 1985 to November 2000. RT was the primary treatment for 32 patients, whereas 12 received RT for residual disease after local ablative therapy. Lesions were located as follows: scalp, 9 patients (20%); face, 12 (27%); trunk, 6 (14%), extremity, 12 (27%), perianal, 3 (7%), and penis, 2 (5%). Orthovoltage X-rays were used in the majority (39 of 44, 89%). There was no standard fractionation regimen: some physicians prescribed high doses, as for invasive skin cancer, whereas others prescribed lower doses because of the noninvasive nature of the disease, a sensitive anatomic location (e.g., extremity), or large treatment area. Because of the variations in fractionation regimens, BED was used as a common metric for biologic effect in the comparison of different regimens and analyzed for correlation with recurrence and toxicity. Local control was defined as the lack of persistent or recurrent disease at the treated site for the follow-up period. Grade 4 toxicity was defined as necrosis (cartilage/bone damage) and/or ulceration for a duration of >3 months. RESULTS: The mean patient age was 67.7 years, and the male/female ratio was 29:15. The median pretreatment lesion size was 2.65 cm(2) (range, 0.07-34.56 cm(2)). Complete remission was achieved in 42 patients, with follow-up unavailable for the remaining 2 patients. Subsequently, 3 patients experienced recurrences at 0.2, 1.1, and 1-1.5 years after complete remission. One recurrence was Bowen's disease (local); the others were squamous cell carcinoma (one local, one marginal). Four patients experienced a new squamous lesion at a distant cutaneous site. As of last follow-up, 32 patients (73%) were known to be alive. Median follow-up was 2.6 years (range, 0-11.8 years). All but 3 patients were disease-free at last follow-up, 1 of whom died with distant, but not local disease. The 5-year overall survival rate was 68%. Biologically effective dose was not associated with recurrence. The crude local control rate was 93%. There was a trend toward higher radiation doses for smaller pretreatment tumor and field sizes. The BED did not correlate with Grade 4 toxicity; however, the three cases of Grade 4 toxicity occurred in patients treated with hypofractionated regimens (dose per fraction >4 Gy) for extremity lesions. CONCLUSIONS: Radiation therapy is an effective treatment option for Bowen's disease of the skin. Local recurrences seem to be equally low in patients treated with high- and low-dose regimens. Avoiding hypofractionated regimens (dose per fraction >4 Gy) in extremity locations might reduce the risk of Grade 4 toxicity.

Erbium:YAG laser pretreatment accelerates the response of Bowen's disease treated by topical 5-fluorouracil.

BACKGROUND: Topical 5-fluorouracil (5-FU) is a standard treatment for Bowen's disease. However, its efficacy may be limited by the presence of stratum corneum. The Er:YAG laser has shown a dramatic enhancement effect on the delivery of 5-FU in vitro by ablation of the stratum corneum. The efficacy of laser-assisted delivery of 5-FU has not been tested in human. OBJECTIVE: To see whether Er:YAG laser pretreatment can improve the efficacy of topical 5-FU in the treatment of Bowen's disease. METHODS: Three target lesions from a patient with multiple Bowen's disease were selected for a half-side comparison study. The Er:YAG laser was used to remove the cornified layer on one side of each lesion, followed by twice-daily application of 5-FU cream to both sides. Clinical and histologic responses were compared. RESULTS: Lesions pretreated with the Er:YAG laser showed more rapid clinical and histologic responses to topical 5-FU than those treated with 5-FU alone. Evaluation at 9 months after treatment showed no recurrences of lesions on both sides. CONCLUSIONS: Our preliminary study demonstrates that this Er:YAG laser-assisted modality is effective and shows accelerated clinical response and shortened treatment time compared with topical 5-FU as a single treatment.

[Cutaneous neoplasms]. / Neoplasien der Haut.

The skin is the organ most commonly affected by malignancies. Various cancers of the skin show a dramatic increase in incidence over the last decades. Epithelial skin tumors are most frequently, e.g., basal cell carcinoma and the squamous cell carcinoma with its precursors, the actinic keratoses. Melanoma, which is extremely difficult to treat in advanced tumor stages, is dreaded. Besides that, there are other epithelial malignant diseases, e.g. Morbus Bowen and adnexal tumors originating from the skin appendices. Mesenchymal malignant neoplasias such as Morbus Kaposi, angiosarcomas and other dermal sarcomas, are rare. Since the majority of malignant neoplasms is removable and curable by a simple surgical intervention, the knowledge of the different skin tumors is essential for non-dermatologist.

[Perianal Bowen's disease: a case report and review of the literature]. / Perianal Bowen's disease: a case report and review of the literature.

Perianal Bowen's disease is a uncommon, slow growing, intraepidermal squamous-cell carcinoma (carcinoma in situ) of the anal region and may be a precursor to squamous carcinoma of the anus. It is associated with cervical and vulvar intraepithelial neoplasia and have human papillomavirus as a common cause. Both sexes and all races are affected, with the highest prevalence in patients aged 20 to 45 years. The symptoms of anal Bowen's disease are unspecific and the clinical findings are uncharacteristic and include pain, itching, bleeding and a disturbing lump. Biopsy and histopathologic examination is required for diagnosis and to distinguish other perianal dermatoses; thus an anogenital warts that fail to respond to conventional therapy, or change in appearance, warrant a biopsy and, where the technique is available, DNA typing to identify the viral pathogen. Infact the etiologic agent, the human papillomavirus (HPV), has been classified by DNA techniques into at least 42 types, of which 16 and 18 are considered to carry a high risk for cancer. The intraoperative findings is a lesion at the anocutaneous line: perianal or intra-anal tumor, erosion or ulceration as well as lichenoid lesion or hyperpigmentation. The disease has a proclivity for recurrence and there are many controversies concerning treatment that effectiveness remains uncertain and range from aggressive wide local excision with skin grafting when necessary to laser vaporization (argon or CO2), radiotherapy or a new immune response modifier (Imiquimod). We report a case of a 50-years-old woman with recurrence of Bowen's disease associated with vulvar HPV infection and review the literature.

Radiation therapy for Bowen's disease: lessons for lesions of the lower extremity.

OBJECTIVE: A retrospective outcomes review of radiotherapy for Bowen's disease was performed to analyze all patients treated with radiation therapy between 1993 and 1997 at the Naval Medical Center, San Diego. METHODS: Eleven patients with 16 lesions were treated with a median time-dose-fractionation value of 105 (range, 93-108). RESULTS: All 11 patients were without evidence of disease within 1 to 2 months of completing treatment. Four of the 16 lesions (25%) were unhealed at time of last follow-up; the remainder healed with good cosmetic result. All unhealed lesions were on the lower extremity. Median follow-up was 27.5 months (range, 9-57 months). CONCLUSION: Radiation remains a good therapeutic option in selected patients with Bowen's disease, but caution should be exercised before selection of patients with lesions in potentially poor healing areas, such as the lower extremity.

Treatment of Bowen's disease with a specially designed radioactive skin patch.

Bowen's disease can be treated by various methods, including surgical excision, cryosurgery, laser ablation, curettage, Mohs' microsurgery and ionizing radiation. Radiotherapy has been a useful therapeutic modality in the treatment of Bowen's disease and other skin cancers in areas which are difficult to excise, especially the central areas of the face, including eyelids, nose and lips. To overcome some of the disadvantages of external radiotherapy, a specially designed skin patch coated with high-energy beta-emitter holmium-166 was made for topical application at our institute. Twenty-nine sites of Bowen's disease in eight patients, confirmed by skin biopsy, were treated with 166Ho patches. The patches were applied to the surface of skin cancers for 30-60 min for a total radiation dose of 35 Gy (3500 rads). One to two weeks after application of the 166Ho patch, desquamation, erythema or erosion developed in treated sites, but these acute radiation reactions healed gradually with epithelial regeneration, and they showed good functional and cosmetic results without any complications. Follow-up biopsies were performed 1-5 months after 166Ho patch therapy, and they did not show any signs of Bowen's disease. One to two years after treatment with 166Ho skin patches, there were no recurrences of Bowen's diseases and no late complications. The 166Ho patch is an effective and convenient alternative method for the treatment of Bowen's disease that yields good cosmetic and functional results.

Bowen's disease of the glans penis (erythroplasia of Queyrat) in plasma cell balanitis.

We report a case of a persistent penile plaque on the glans penis of allegedly more than 20 years' duration, which was refractory to circumcision and local treatment. Over the years, the patient repeatedly presented with a circumscribed inflammatory lesion of the glans penis, diagnosed as Zoon's balanitis on the basis of clinical aspects and two biopsies. Because of unresponsiveness of the lesion to circumcision and focal steroid infiltration, repeated biopsies were performed in an attempt to rule out malignancy. Two further biopsies were carried out. One again showed the features of a plasmacellular inflammation, while the other finally revealed the histopathologic features of erythroplasia of Queyrat (carcinoma in situ or Bowen's disease of the glans penis). We assume that either the former biopsy specimens were taken from a plasma cell-rich reactive infiltrate around the neoplastic lesion, or that carcinoma in situ may have arisen due to the chronic inflammation of Zoon's balanitis plasmacellularis. Radiotherapy was performed with good clinical response and subsequent histopathologic proof of complete remission of the lesion.