Weather conditions and daylight-mediated photodynamic therapy: protoporphyrin IX-weighted daylight doses measured in six geographical locations.

BACKGROUND: Photodynamic therapy (PDT) is an attractive therapy for nonmelanoma skin cancers and actinic keratoses (AKs). Daylight-mediated methyl aminolaevulinate PDT (daylight-PDT) is a simple and painless treatment procedure for PDT. All daylight-PDT studies have been performed in the Nordic countries. To be able to apply these results in other parts of the world we have to compare the daily protoporphyrin IX (PpIX) light dose in other countries with the PpIX light doses found in Nordic countries. OBJECTIVES: To calculate where and when daylight-PDT of AKs was possible in six different geographical locations using ground stations measuring PpIX-weighted daylight doses. METHODS: PpIX-weighted daylight doses were measured using a dosimeter with a customer-specific photodiode with a detector sensitivity that mimics the PpIX absorption spectrum and measures in 'PpIX doses'. The dosimeters were built into ground stations that were placed in six geographical locations measuring from July to December 2008. Temperature data for each location were obtained from the internet. The maximal ultraviolet (UV) index for Copenhagen was obtained for the measuring period of the dosimeters. RESULTS: If the PpIX light dose should be above 8Jcm(-2) and the maximum temperature of the day at least 10°C, it was possible to treat patients on nearly all days until the middle of September in Reykjavik and Oslo, until the last week of October in Copenhagen and Regensburg, until the middle of November in Turin and all year in Israel. CONCLUSIONS: Where and when to perform daylight-PDT depends on the PpIX light dose and outdoor temperature. The PpIX light dose was influenced by the geographical location (latitude), weather condition and time of year. The UV index was not more suitable than temperature and weather to predict if the intensity of daylight would be sufficient for daylight-PDT.

Expression of matrix metalloproteinase (MMP)-7 and MMP-13 and loss of MMP-19 and p16 are associated with malignant progression in chronic wounds.

BACKGROUND: The risk of squamous cell carcinoma (SCC) is significantly increased in chronic leg ulcers. Very little is known about the molecular pathogenesis of these tumours, which are often undiagnosed for a long time. As matrix metalloproteinases (MMPs) are implicated at all stages of tumorigenesis, we investigated whether the pattern of epithelial MMP expression can predict development of SCC from pseudoepitheliomatous hyperplasia of chronic wounds. METHODS: Samples from nine patients with SCCs that had arisen in chronic wounds and 31 with venous leg ulcers were studied using immunohistochemistry for MMP-7, MMP-8, MMP-9, MMP-13, MMP-19 and the tumour suppressor p16. In situ hybridization was performed for MMP-1, MMP-3, MMP-7, MMP-12 and MMP-13. RESULTS: MMP-7 was expressed by malignantly transformed epithelium, while it was absent from chronic wounds. MMP-9 was detected in the epithelium in both SCCs and chronic wounds. Epithelial MMP-13 expression was strong in SCC, but was absent in chronic wounds. MMP-12 was expressed in the epithelium in two SCCs, while macrophages were positive in chronic wounds. MMP-19 was induced in proliferating epithelium of wounds, but was absent from invasive areas of SCC. p16 was expressed by keratinocytes in half of the chronic wounds and at superficial margins of SCCs, while invasive areas were negative. CONCLUSIONS: Our results suggest that epithelial expression of MMP-7, MMP-12 and MMP-13, but not that of MMP-1, MMP-3, MMP-8, MMP-9 and MMP-10, in chronic wounds provides a diagnostic clue for distinguishing SCCs from nonmalignant wounds. The loss of MMP-19 and p16 from the epithelium could aid in making the differential diagnosis between well-differentiated SCCs and nonmalignant chronic wounds.

Expression of p21WAF1/CIP1, p53, bcl-2 and Ki-67 in venous leg ulcers with and without squamous cell carcinoma.

In order to gain understanding of the cellular mechanisms of malignant transformation in chronic venous leg ulcers, we analysed by immunohistochemistry the presence of p21, p53, bcl-2 and Ki-67 in ulcers with and without squamous cell carcinoma. The material consisted of 41 archived histopathological samples from 33 patients with chronic venous leg ulcers and 28 samples from 21 patients suffering from squamous cell carcinoma in chronic venous leg ulcers. All samples derived from the chronic ulcers were negative for p53, p21 and bcl-2. Cells positive for Ki-67 were seen in certain ulcer areas. In the cancers, 14 samples showed immunopositivity for p53 and 22 samples were positive for p21, with expression mainly in the suprabasal layer. Expression of p21 seemed independent of p53. None of the samples was bcl-2-positive. Ki-67 was positive with basal expression in 16/28 of the tumour samples, 15 of which also expressed p21. There was no perilesional p53 or p21 activity in the cancer samples. The results regarding perilesional expression are different from those reported in UV-induced squamous cell carcinomas and probably reflect a different carcinogen.

Human papillomavirus in venous ulcers with and without squamous cell carcinoma.

Malignant transformation of chronic wounds is a well-known, albeit rare, phenomenon. We examined archival paraffin blocks of samples of squamous cell carcinoma (SCC) in chronic venous leg ulcers previously taken from 23 patients and of chronic noncancerous venous leg ulcers from 35 patients for the presence of human papillomavirus (HPV) DNA. The methods used were the polymerase chain reaction (PCR) with GP05+/06+ (mucosal) and nested PCR with CP65/70 and CP66/69 (EV-associated) primers. A subsequent nonradioactive Southern blot hybridization was used to confirm the specificity of the PCR. With PCR three samples were positive on the gel, and with Southern blotting, a further seven samples were positive, to give a total of ten samples. All of the positive samples were from the noncancerous ulcers and with the primers GP05+/06+. HPV infection is probably not the carcinogen responsible for the malignant transformation of venous leg ulcers. The difference in positivity between the ulcers and the SCCs was statistically significant (P = 0.01) and raises the question as to whether HPV-positive cells are eliminated in the interaction between the SCC and the immune system. Further studies on the carcinogenic effects of chronic proliferation and the role of HPV infection therein, are needed.

Squamous cell carcinoma complicating chronic venous leg ulceration: a study of the histopathology, course and survival in 25 patients.

We have studied 25 cases of squamous cell carcinoma in chronic venous leg ulcers. Twenty-three of the patients were dead and two were alive. The mean age at cancer diagnosis was 78.5 years. The median survival was 1 year. Eleven tumours were well-differentiated, 10 moderately and four poorly. All patients with a poorly differentiated tumour died within a year. Metastases were certain in eight cases. The disease was lethal in 10 cases which included all poorly differentiated tumours. The survival of the study group was significantly shortened compared with a control group of patients with lower limb non-melanoma skin cancer (n = 433) from the Swedish Cancer Registry (P = 0.0084). When diagnosed, squamous cell carcinoma in chronic leg ulcers merits a thorough investigation of the degree of differentiation and spread. Assertive treatment is indicated as poorly differentiated tumours and some moderately differentiated tumours may be fatal.

Venous leg ulcers and squamous cell carcinoma: a large-scale epidemiological study.

In order to obtain a precise estimate of the relative risk of squamous cell carcinoma (SCC) in venous leg ulcers, we matched 10,913 patients with the diagnosis venous leg ulcer from the Swedish Inpatient Registry with registrations of SCC of the lower limb recorded by the Swedish Cancer Registry, and found 33 cases of non-melanoma skin cancer. After scrutinizing the pathology and case records, 17 cases of SCC were considered as being certainly secondary to venous leg ulcers, whereas in six cases of remitting/relapsing ulcers the connection was probable. The relative risk calculated on 17 cases was 5.80 (95% confidence interval = 3.08-9.29). The median duration of the ulcer before the diagnosis of cancer was 25 years. The mean follow-up time of the cohort was 8.5 years. We conclude that SCC is a complication of chronic venous leg ulcers, although the absolute risk is very small.

Leg ulcers and squamous cell carcinoma. An epidemiological study and a review of the literature.

There has been concern about the possible risk of malignification of venous leg ulcers. To investigate the incidence of squamous cell carcinoma in venous ulcers, data on 1,170 patients with venous leg ulcers and 511 patients with other types of non-traumatic ulcers were matched with corresponding data from the Swedish Cancer Registry to determine the incidence of squamous cell carcinoma in these patients. Mean follow-up time was 8.3 years. Seven cases of squamous cell cancer were observed, while the expected number was 10.56 (relative risk = 0.66; 95% confidence interval = 0.27 to 1.36). However, four of the observed cancers were located on the lower leg in venous ulcers, the expected number being 0.68 (relative risk = 5.89; 95% confidence interval = 1.60 to 15.08). This indicates that a certain alertness is necessary when treating this common disease. The literature on cancer in venous ulcers, where 152 cases of squamous cell carcinoma in venous ulcers are reported, is reviewed.