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Background Photodynamic therapy (PDT) in combination with stent have shown promising results in the treatment of biliary tract cancer (BTC) in patients not suitable for surgery. Chemotherapy has been shown to improve survival in patients with local advanced and metastatic BTC. Material and methods In the current randomized trial the combination of chemotherapy and stent with and without temoporfin (Foscan) photodynamic therapy (PDT), with a primary endpoint on feasibility and safety, has been performed. Ten patients in each group. Results No serious, acute procedure-related complication related to PDT or the treatment combination was seen. The number of patients with cholangitis was equal in both groups. In the PDT group – arm A – two patients had cutaneous erythema after sun exposition, one of them with a localized blister. No neutropenic infection was seen. Quality of Life (QoL) was similar in both treatment groups. Progression free survival was numerically longer in the PDT group. Conclusion The treatment combination was feasible. There was no serious complication related to PDT or the treatment combination. Number of cholangitis was equal in both groups, two abscesses were observed in the PDT group. Progression free survival was numerically longer in the PDT group.

SummaryBackground Genital erosive lichen planus (GELP) in women is a chronic inflammatory disease characterized by painful vulval and vaginal erosions. Topical photodynamic therapy (PDT) is increasingly used in premalignant and malignant diseases and may have an effect in inflammatory diseases. Objectives To assess the feasibility, efficacy and safety of hexyl 5-aminolevulinate-hydrocloride (HAL)-PDT in GELP. Methods Forty women, diagnosed with GELP at a specialized vulva clinic, were randomized to one session HAL-PDT in vulva and/or vagina (n = 20) or daily applications of clobetasol propionate 0·05% ointment in vulva and optional hydrocortisone acetate 1·0% foam in vagina for 6 weeks (n = 20). After 6 weeks, all patients were allowed to use topical corticosteroids as needed. Clinical examinations were performed at weeks 0, 6 and 24, using a clinical score developed for the study. All patients wrote a weekly log on pain, topical corticosteroid use and adverse events. Results Three patients, all in the corticosteroid group, withdrew from the study after 1–3 weeks. The mean reduction in clinical scores was similar in the PDT group and the corticosteroid group; 25% vs. 22% after 6 weeks (P = 0·787) and 35% vs. 38% after 24 weeks (P = 0·801). The mean reduction in pain visual analogue scale scores was 38% vs. 55% after 6 weeks (P = 0·286) and 39% vs. 12% after 24 weeks (P = 0·452). Patients in the PDT group reported significantly less topical corticosteroid use during weeks 7–24 than those in the corticosteroid group. No major adverse events were reported. Conclusions Vulvovaginal HAL-PDT seems to be an effective and safe treatment for GELP.

Summary Genital erosive lichen planus (GELP) is a chronic inflammatory disease, in women characterized by painful vulvar and vaginal erosions. To prepare for a clinical trial on photodynamic treatment (PDT), we applied hexyl 5-aminolevulinate hydrochloride (HAL) in clinically normal and affected mucosa in 12 women with GELP using two different doses (6.25 or 50 mg/ml). Biopsies were taken after 30 min and 3 h. The biodistribution of HAL, measured as photoactive protoporphyrin IX (PpIX), was studied using non-invasive superficial fluorescence measurements and microscopic fluorescence photometry. More PpIX was detected after application of 12.5 mg HAL than after 100 mg, with large inter-individual variations. PpIX levels after 3 h were overall higher than after 30 min. PpIX fluorescence was not detected in skin distant to the genital area. In conclusion, 6.25 mg/ml HAL applied for 3 h seems adequate for HAL absorption and conversion to PpIX in submucosal inflammatory and epithelial cells and can be used in a PDT trial of GELP.

Purpose To investigate whether a combination of self-expanding metal stent (SEMS) and brachytherapy provided more rapid and prolonged effect on dysphagia without increased pain compared to brachytherapy alone in patients with incurable oesophageal cancer. Methods 41 Patients were randomised to SEMS followed by brachytherapy, 8Gy×3 (n=21) or brachytherapy alone, 8Gy×3 (n=20). Change in dysphagia and pain three and seven weeks after randomisation (FU1 and FU2) was assessed by patient-reported outcome. Dysphagia, other symptoms and health-related quality of life were assessed every four weeks thereafter. The study was closed before the estimated patient-number was reached due to slow recruitment. Results Patients receiving SEMS followed by brachytherapy had significantly improved dysphagia at FU1 compared to patients receiving brachytherapy alone (n=35). Difference in pain was not observed. At FU2, patients in both arms (n=21) had less dysphagia. Four patients in the combined treatment arm experienced manageable complications, no complications occurred after brachytherapy alone. Conclusion For the relief of dysphagia, SEMS followed by brachytherapy is preferable and safe for patients in need of immediate alleviation, while brachytherapy with or without preceding SEMS provides relief within a few weeks after treatment.

Background and Aims: A significant change in the occurrence of oesophageal squamous cell carcinomas (SCCs) in relation to adenocarcinomas (ACs) has been observed in the Norwegian population during the last 20 years (1988–2007). The AC incidence has increased from 5–10% to more than 50% nowadays, while the incidence of SCCs has decreased. Our goal was to evaluate if the change from SCC to AC and the increased effort to control reflux could be reflected in tumour stage, patient demographics and treatment results. Material and Methods: We analysed clinical and pathological data from 347 patients with oesophageal AC (n = 189) and SCC (n = 158) treated at The Norwegian Radium Hospital during said period for patient- and tumour characteristics, treatment modalities and survival. Results: An oesophageal resection was performed in 169 of 347 patients. The median survival rate for all patients was 15 months, with a 5-year survival rate of 10%. The median survival time for operated and non-operated patients was 25 and 12 months respectively, with the corresponding 5-year survival rate of 13% and 2%. Patients with N0M0 disease operated with free resection margins presented a 5-year survival rate of 28%. Conclusions: The change from SCC to AC and the ensuing considerable efforts made in surveillance and treatment of AC did not lead to improved long time survival for our patients.

Over a 10-year period from 1990, 445 patients with carcinoma of the oesophagus were admitted to the Norwegian Radium Hospital and 184 of these patients received treatment with curative intent. Even though surgery is the treatment of choice for these patients, many of them suffer from medical conditions that increase the risk for postoperative mortality and morbidity. In a retrospective study, the effect of the curative treatment offered to patients was explored with a particular focus on patients unfit for surgery.Medical data of the 184 patients treated with curative intent were reviewed and additional clinical information was retrieved from local hospitals and general practitioners. Preoperative radiotherapy followed by surgery was the standard curative treatment for operable patients. Medically inoperable patients were offered radical split-course hyperfractionated radiotherapy followed by a brachytherapy boost.More than 50% (103/184) received non-surgical treatment only. Patients who received radical surgery (n = 81) were younger, had better performance status, less weight loss and dysphagia compared to patients treated with radical radiotherapy (n = 102). One patient received only photodynamic therapy. The 3-year survival was 29% for patients treated with radical surgery, and 8% for patients who received radical radiotherapy. The overall median crude survival for the two groups of patients were 20 months and seven months respectively.The hyperfractionated radiotherapy provided symptom relief without extensive toxicity and with a possibility for cure for patients with oesophageal cancer who are unfit for surgery and chemoradiotherapy. The literature supports the curative potential of high dose accelerated hyperfractionated radiotherapy even though the optimal radiotherapy regimen still needs to be explored.

Long-term follow-up data are needed to evaluate treatment effect after photodynamic therapy (PDT).To investigate long-term clinical, histological and cosmetic follow-up results in basal cell carcinoma (BCC) after PDT, including treatment response related to patients and lesion characteristics.A longitudinal study of 44 patients with 60 histologically verified BCC tumours, treated with one or two sessions of dimethylsulfoxide (DMSO)-supported 5-aminolaevulinic acid--PDT following curettage, was performed. Lesions in complete remission after 3 months were followed with clinical inspection, histological investigation and evaluation of cosmetic outcome at regular intervals; long-term efficacy assessed as verified recurrence within 72 months after PDT.Complete remission at 3 months was achieved in 55 lesions from 39 patients. Two patients with one lesion each died. At 72 months, 43 of 53 lesions remained disease-free (81%); 68% remained after one treatment session, and 91% remained after two treatment sessions. Recurrence of tumour occurred at 6, 12, 24 and 36 months in 2, 4, 2 and 2 lesions, respectively; clinical investigation identified 97% of them. Male sex and H-mid-face zone were significantly associated with recurrence. The cosmetic outcome at 72 months was rated as good or excellent by patients and investigators in more than 90% of evaluated cases.DMSO-PDT following curettage is an effective treatment for BCC, with favourable long-term clinical, histopathological and cosmetic results. Clinical examination of treated lesions appears to be sufficient for long term follow up.

Topical photodynamic therapy (PDT) of superficial basal cell carcinoma (BCC) with 5-aminolevulinic acid (ALA) has achieved promising clinical results. However, the efficacy of this therapy for thick BCC is dramatically decreased by a limited diffusion of hydrophilic ALA into the tumor. Lipophilic esters of ALA may enhance their penetration into the lesion. In this randomized, open clinical study, microscopic fluorescence photometry incorporating a light-sensitive thermo-electrically cooled charge-coupled device (CCD) camera was employed to investigate the penetration of methyl 5-aminolevulinate-induced porphyrin fluorescence in thick BCC lesions. Both the distribution pattern and the amount of porphyrins in 32 lesions of 16 patients were studied after topical application of 16, 80 or 160 mg/g of methyl 5-aminolevulinate for 3 or 18 h. A highly selective and homogeneous distribution of methyl 5-aminolevulinate-induced porphyrin fluorescence was seen in all lesions studied, with much less fluorescence in the adjacent normal skin tissues. In lesions of up to 2 mm thickness the application of 160 mg/g methyl 5-aminolevulinate for 3 h showed the highest ratio of porphyrin fluorescence depth to tumor depth (0.98+/-0.04), thus providing a biologic rationale for a clinical PDT trial with this regimen.

Clonal chromosome abnormalities were found in 22 of 23 short-term cultured basal cell carcinomas (BCC) of the skin. The karyotypic abnormalities were nonrandom and in several cases included evidence of clonal evolution. Especially in cultures showing an epithelial growth pattern, simple numerical changes, most commonly +18, +9, +20, +7, and +5, predominated and presumably constitute pathogenetically important aberrations present in the neoplastic parenchyma. Also, several structural rearrangements of chromosome arm 9q were seen, which may be of particular interest against the background that a gene for familial BCC (Gorlin syndrome), the PTCH gene, maps to this region. Finally, most of the clonal aberrations detected in predominantly fibroblast-like cultures are likely to reflect changes acquired by cells of the tumor stroma, which raises the question whether mutations also of this tumor component may play a pathogenetic role in BCC development.

Objectives: Urinary bladder urothelial carcinoma is diagnosed by a combination of cystoscopy and biopsy, with cytology as a valuable additional technique. The accuracy of cytological diagnosis depends on the experience of the cytologist and can inevitably vary from one cytologist to another. There is a need for an easy, reliable and objective diagnostic method. In the present study a new method was designed for the detection of bladder cancer cells in urine. Methods: Flow cytometry was utilized to detect protoporphyrin IX in an artificial model consisting of normal urinary bladder transitional epithelial cells (NBECs) from healthy volunteers’ urine and an established human urinary bladder carcinoma cell line, TCCSUP, after incubation with hexaminolevulinate (HAL). In addition, urine samples from 19 patients with histopathologically confirmed superficial bladder cancer were examined. Results: Incubation of NBECs or TCCSUP cells with HAL for 1 hour resulted in production of protoporphyrin IX only in the TCCSUP cells. Incubation of a mixture of NBECs and TCCSUP cells with HAL gave rise to a separated subpopulation of cells with protoporphyrin IX fluorescence. After cell sorting by flow cytometry the protoporphyrin IX-containing subpopulation of cells was confirmed as TCCSUP cells on cytological examination. It was possible to detect 5% TCCSUP cells in the mixture of NBECs/TCCSUP cells. To test the feasibility of the method in clinica diagnosis, urine samples from patients with bladder cancer were also measured with comparable, although preliminary and limited, results to those of cytological examination. Conclusions: The preliminary results show that the technique may be feasible for the detection of bladder cancer cells in urine with possible advantages of simplicity, reliability and objectivity.

Up to 90% of patients with localized non-Hodgkin's lymphomas (NHL) in the gastrointestinal tract (GI) are cured and decreased use of radical surgery is favoured. Although quality of life (QOL) may impact treatment choice, little is known about QOL in gastric NHL survivors. The self-reported QOL (EORTC QLQ-C30 and a gastric module) and objective findings from upper GI endoscopy were evaluated in patients in complete remission after treatment for primary gastric NHL at the Norwegian Radium Hospital (NRH). Thirty-six (90%) patients completed the questionnaires, 33 (83%) met for endoscopy. Ten patients were treated with total gastrectomy, 17 with partial gastrectomy, while nine patients did not undergo surgery. Gastroscopy was normal in 55% of the non-gastrectomised patients, oesophagoscopy in 69%. Four patients had Barrett's metaplasia. QOL was not different from population values. Patients treated with total gastrectomy reported poorer emotional function, more diarrhoea and more food-related problems (por =0.05) compared with the others. Based on the higher level of digestive and food related problems after total gastrectomy, stomach-preserving surgery should be preferred whenever possible.

Photodynamic therapy using topical methyl 5-aminolevulinate (MAL) is a new treatment modality for basal cell carcinoma (BCC) and actinic keratosis (AK). MAL induces endogenous porphyrins, which act as photosensitizers. Pharmacokinetic studies of the porphyrin-inducing effect of MAL creams (Metvix®) applied in different concentrations (16–160 mg/g) and application times are presented. Surface fluorescence measurements were used to monitor porphyrin accumulation in 18 superficial BCCs and 32 AKs. For both lesion types, the fluorescence increased during the first 13 of 28 hours of continuous MAL application. A 20-fold site-to-site variation was observed, and there were no significant MAL concentration dependencies. The selectivity between lesions and normal skin was 10-fold during the first hours and decreased throughout the application time. Fluorescence microscopy images of tissue sections from 32 nodular BCCs were analyzed to calculate the porphyrin content in tumor tissue as a function of depth. Significant correlation to MAL concentration was seen within the tumors treated for 3 hours. Increase to 18-hour MAL application enhanced the fluorescence levels in superficial tumor layers, but not in deep layers. In conclusion, application of the 160 mg/g cream for 3 hours gave advantageous porphyrin distributions for all types of lesions.

OBJECTIVE: Anyang County, China, is one of the areas with the highest incidence of esophageal cancer in the world. Esophageal cancer has a poor prognosis because most tumors are unresectable at the time of diagnosis. We launched a screening study for early esophageal carcinoma in western Anyang County in 1997. The scope was to identify patients with in situ and early invasive carcinoma, applying esophageal balloon cytology and treating with photodynamic therapy (PDT). STUDY DESIGN: The study cohort consisted of all inhabitants over 35 years of age in 10 communes. Screening was performed by balloon cytology. Grade 2 dysplasia and more advanced lesions were examined with endoscopy, including biopsy and brush cytology, followed by PDT for early cancer. RESULTS: In total, 20,049 persons participated in the screening program, and 1,018 were diagnosed with a grade 2 dysplasia or higher, including 164 invasive cancers and 169 near-cancers. Ninety-four percent of atypical lesions were of squamous cell type. Seventy-two percent of cases showing severe dysplasia and cancer were located to the middle esophageal segment. The prevalence of dysplasia and cancer increased significantly with age. The balloon cytology results were confirmed by brush cytology and histology. CONCLUSION: Balloon cytology is a reliable method for esophageal cancer screening. Positive cytology must be verified by endoscopy and biopsy.

Summary Background Methyl 5-aminolaevulinate (mALA) is an ester derivative of 5-aminolaevulinic acid (ALA) with increased lipophilicity compared with ALA. Objectives To assess long-term cure rate, cosmesis, recurrence rate and extent of fibrosis after mALA-based photodynamic therapy (PDT) of superficial and nodular basal cell carcinomas (BCCs) showing early complete response to treatment. Methods Of 350 BCCs treated, 310 responded completely. These were in 59 patients who were followed for 2‐4 years (mean 35 months) after mALA-PDT. Nodular tumours were curetted before PDT, and mALA 160 mg g 21 was applied to all tumours for 24 h or 3 h before illumination from a broad-band halogen light source with light doses from 50 to 200 J cm 22 . Fibrosis was assessed histologically in 23 biopsies. Results The overall cure rate for 350 BCCs, including non-responders and recurrences was 79%. Of 310 lesions, 277 (89%) remained in complete response, and the cosmetic outcome was excellent or good in 272 of the completely responding lesions (98%). Histological examination showed dermal fibrosis in one of 23 biopsies. Conclusions We conclude that mALA-based PDT with prior curettage of nodular lesions is a promising new method for the treatment of BCC.

This study was conducted to assess the efficacy of aminolevulinic acid-based photodynamic treatment for residual or recurrent basal cell carcinomas after radiotherapy. Photodynamic therapy with either topical 5-aminolevulinic acid 20% and dimethylsulfoxide 99% pretreatment or topical methylester aminolevulinic acid 20% w/w in cream and subsequent light illumination of 50-200 J/cm2 was performed after an initial skin shaving procedure in 20 patients with 22 residual or recurrent basal cell carcinomas. Three lesions were treated once, while twelve, three, one and two lesions received two, three, four and five treatment sessions respectively. At examination, 6-40 months (mean 22 months) after the last treatment, 18 lesions were in complete remission. All lesions were considered excellent or good with regard to cosmetic outcome. Three lesions responded only partially to photodynamic therapy and a fourth lesion recurred 21 months after photodynamic treatment. Two of these four lesions were confirmed as the morpheaform type of basal cell carcinoma.

Photodynamic therapy is a new mode of cancer treatment with promising results for basal cell carcinoma. The current study aims to investigate the accuracy of skin scrape cytology in the diagnosis of basal cell carcinoma as an integrated part of the treatment procedure. A total of 107 nodular basal cell carcinomas of the skin from 90 patients were examined and cytological and histological diagnoses were compared. Compared with histopathology, cytopathology gave 3 false benign results (2.8%) and no false malignant diagnoses. Three lesions were benign by both methods. We conclude that basal cell carcinoma is reliably diagnosed with both techniques. However, cytology is simpler and faster, allowing treatment to be instituted shortly after the first consultation.

By means of a chemical extraction procedure and confocal laser scanning microscopy, we investigated the kinetic patterns of uptake and biolocalization of 5-aminolevulinic acid (ALA)-induced porphyrins in s.c. transplanted tumors, adjacent normal skin and muscle, and liver of mice bearing mammary carcinoma, after i.p. injection of 250 mg/kg ALA or topical application of ALA (20% in an oil-in-water emulsion). Furthermore, we evaluated the tumor responses after either i.p. injection or topical application of 5-ALA followed by laser irradiation (632 nm, 150 mW/cm2, 25 min) by measuring the treated tumor regression/regrowth time and by light and electron microscopy. Strong fluorescence of ALA-induced porphyrins was detected in the tumor, skin and liver tissues, while little fluorescence was seen in the adjacent muscle tissue. Moreover, the highest amounts of ALA-induced porphyrins in the tumor and skin tissues were found 1 hr after i.p. injection, whereas the amounts of the porphyrins in both tissues increased with increasing time after topical application of ALA. The fluorescence of the porphyrins was localized in several components of the skin tissue (epidermis, hair follicles and their associated sebaceous glands). Furthermore, the fluorescence was diffusely distributed in the s.c. transplanted tumor tissue. Little could be observed under a confocal laser scan microscope (CLSM) in the muscle tissue. The uptake and biolocalization data correlate well with the results of PCT efficiency of the same tumor model with ALA-induced porphyrins. Light and electron microscopy showed that the mitochondria of the tumor cells and of the endothelial cells and the basal lamina of vascular walls beneath the endothelium in the tumor tissue were initially extensively destroyed after PCT with ALA-induced porphyrins. Thereafter, diffuse degeneration followed by local and/or diffuse severe necrosis of the tumor cells was found. This may be due mainly to the initial damage to mitochondria in the cancerous and endothelial cells and also to the destruction of the vascular wall in the tumor tissue. © 1992 Wiley-Liss, Inc.

The aim of this prospective randomized study was to compare the clinical and cosmetic outcome of superficial basal cell carcinomas (BCC), using either laser or broadband halogen light, in photodynamic therapy with topical 5-aminolevulinic acid (ALA). A total of 83 patients with 245 superficial BCC were included in the study. Standard treatment involved 15 min of local pretreatment with 99% dimethylsulfoxide (DMSO) before topical application of 20% ALA with DMSO (2%) and ethylendiaminetetraacetic acid (2%) as cofactors for 3 h before light exposure with either laser or a broadband lamp (BL). A complete response was achieved in 95 lesions (86%) in the laser group and 110 lesions (82%) in the BL group 6 months after treatment. Of these, 80 lesions (84%) in the laser group and 101 lesions (92%) in the lamp group were independently evaluated to have an excellent or good cosmetic post-treatment score. No serious adverse events were reported. This study shows that there is no statistical significant difference in cure the rate (P = 0.49) and the cosmetic outcome (P = 0.075) with topical application of a modified ALA-cream between light exposure from a simple BL with continuous spectrum (570-740 nm) or from a red-light laser (monochromatic 630 nm). Cost and safety are further elements in favor of the BL in this setting.