Topological methods for the comparison of structures using LDR-brachytherapy of the prostate as an example.

The dose coverage of low dose rate (LDR)-brachytherapy for localized prostate cancer is monitored 4-6 weeks after intervention by contouring the prostate on computed tomography and/or magnetic resonance imaging sets. Dose parameters for the prostate (V100, D90 and D80) provide information on the treatment quality. Those depend strongly on the delineation of the prostate contours. We therefore systematically investigated the contouring process for 21 patients with five examiners. The prostate structures were compared with one another using topological procedures based on Boolean algebra. The coincidence number C(V) measures the agreement between a set of structures. The mutual coincidence C(i, j) measures the agreement between two structures i and j, and the mean coincidence C(i) compares a selected structure i with the remaining structures in a set. All coincidence parameters have a value of 1 for complete coincidence of contouring and 0 for complete absence. The five patients with the lowest C(V) values were discussed, and rules for contouring the prostate have been formulated. The contouring and assessment were repeated after 3 months for the same five patients. All coincidence parameters have been improved after instruction. This shows objectively that training resulted in more consistent contouring across examiners.

A 5-year follow-up study for distance visual acuity after low dose radiation on subfoveal choroidal neovascularization in age-related macular degeneration.

In a prospective study with a 5-year follow-up, we assessed the effect of a single series of low-dose radiation on the distance visual acuity in eyes with angiographically confirmed subfoveal choroidal neovascularization (CNV) in age-related macular degeneration (ARMD). The posterior pole of 12 eyes was treated with 5 Gy (4 x 1.25 Gy), and 34 eyes treated with 8 Gy (4 x 2 Gy). The best corrected distance visual acuity was measured at the time of treatment, and annually thereafter for 5 years. The study obtained complete follow-up for 11 patients in the 5-Gy group (nine classic, two occult CNVs), and 29 patients in the 8-Gy group (12 classic, 17 occult CNVs). At baseline, the mean distance visual acuity of the treated eyes was 0.16 (20/125) in the 5-Gy group, and 0.2 (20/100) in the 8-Gy group. Five years later, an average loss of 3.2 lines was present in the 5-Gy group, and 4 lines in the 8-Gy group. After 5 years, an average loss of 2 lines was found in a control group consisting of 18 second eyes with low stage dry ARMD, with a mean distance visual acuity of 0.5 (20/40) at baseline. Statistical analyses with Wilcoxon and Mann-Whitney U-tests showed that a single series of low dose radiation with either 5 Gy or 8 Gy was not able to stabilize the distance visual acuity of eyes with subfoveal CNV in ARMD during a 5-year follow-up.

UV-damage-mediated induction of homologous recombination in Arabidopsis is dependent on photosynthetically active radiation.

Plants are continuously subjected to UV-B radiation (UV-B; 280-320 nm) as a component of sunlight causing damage to the genome. For elimination of DNA damage, a set of repair mechanisms, mainly photoreactivation, excision, and recombination repair, has evolved. Whereas photoreactivation and excision repair have been intensely studied during the last few years, recombination repair, its regulation, and its interrelationship with photoreactivation in response to UV-B-induced DNA damage is still poorly understood. In this study, we analyzed somatic homologous recombination in a transgenic Arabidopsis line carrying a beta-glucuronidase gene as a recombination marker and in offsprings of crosses of this line with a photolyase deficient uvr2-1 mutant. UV-B radiation stimulated recombination frequencies in a dose-dependent manner correlating linearly with cyclobutane pyrimidine dimer (CPD) levels. Genetic deficiency for CPD-specific photoreactivation resulted in a drastic increase of recombination events, indicating that homologous recombination might be directly involved in eliminating CPD damage. UV-B irradiation stimulated recombination mainly in the presence of photosynthetic active radiation (400-700 nm) irrespective of photolyase activities. Our results suggest that UV-B-induced recombination processes may depend on energy supply derived from photosynthesis.

Elevated UV-B radiation reduces genome stability in plants.

Long-term depletion of the stratospheric ozone layer contributes to an increase in terrestrial solar ultraviolet-B radiation. This has deleterious effects on living organisms, such as DNA damage. When exposed to elevated ultraviolet-B radiation (UV-B; 280-315 nm), plants display a wide variety of physiological and morphological responses characterized as acclimation and adaptation. Here we show, using special sun simulators, that elevated solar UV-B doses increase the frequency of somatic homologous DNA rearrangements in Arabidopsis and tobacco plants. Increases in recombination are accompanied by a strong induction of photolyase and Rad51 gene expression. These genes are putatively involved in major DNA repair pathways, photoreactivation and recombination repair. In mutant Arabidopsis plants that are deficient in photoreactivating ultraviolet-induced cyclobutane pyrimidine dimers, recombination under elevated UV-B regimes greatly exceeds wild-type levels. Our results show that homologous recombination repair pathways might be involved in eliminating UV-B-induced DNA lesions in plants. Thus, increases in terrestrial solar UV-B radiation as forecasted for the early 21st century may affect genome stability in plants.

Prognostic factors in urothelial renal pelvis and ureter tumours: a multicentre Rare Cancer Network study.

To assess the prognostic factors in patients with transitional-cell carcinoma of the renal pelvis and/or ureter, a series of 138 patients with transitional-cell carcinoma of the renal pelvis and/or ureter was collected in a retrospective multicentre study. 12 patients with distant metastases were excluded from the statistical evaluation. All but 3 patients underwent radical surgery: nephroureterectomy (n = 71), nephroureterectomy and lymphadenectomy (n = 20), nephroureterectomy and partial bladder resection or transurethral resection (n = 20), nephrectomy (n = 10), and ureterectomy (n = 5). Sixty-one per cent (n = 77) of the tumours were located in the renal pelvis, and 21% (n = 27) in the ureter (both in 22 [17%]). Following surgery, residual tumour was still present in 33 patients (16 microscopic and 17 macroscopic). Postoperative radiotherapy was given to 45 (36%) patients. The median follow-up period was 39 months. In a median period of 9 months, 66% of the patients relapsed (34 local, 7 locoregional, 16 regional, and 24 distant). The 5- and 10-year survival were 29% and 19%, respectively, in all patients. In univariate analyses, statistically significant factors influencing the outcome were Karnofsky index, pT-classification, pN-classification, tumour localisation, grade, and residual tumour after surgery. Multivariate analysis revealed that independent prognostic factors influencing outcome were pT-classification, the existence of residual tumour, and tumour localisation. In patients with urothelial renal pelvis and/or ureter tumours, a radical surgical attitude is mandatory; and the presence of tumour in the ureter is associated with a poorer prognosis.

Differential antigen-processing pathways of the hepatitis B virus e and core proteins.

BACKGROUND & AIMS: Hepatitis B e antigen (HBeAg) and hepatitis B core antigen (HBcAg) seem to play different roles in the induction and regulation of the antiviral immune response, although the two antigens share all major CD4(+) T-cell epitopes, and these epitopes can be processed from both antigens via the exogenous antigen-presenting pathway. The aim of this study was to test the ability of antigen-presenting cells to present epitopes from endogenously synthesized HBcAg/HBeAg on HLA class II molecules. METHODS: Lymphoblastoid cell lines infected with recombinant vaccinia viruses containing various HBcAg or HBeAg constructs and stable transfectants were tested for their ability to stimulate HBcAg/HBeAg-specific CD4(+) T-cell clones. RESULTS: Only antigen-presenting cells infected with HBeAg constructs but not those infected with HBcAg constructs were able to stimulate HBcAg/HBeAg-specific CD4(+) T-cell clones. T-cell activation by HBeAg constructs was completely inhibited by brefeldin A but not affected by chloroquin. In contrast, T-cell activation by exogenous, recombinant HBcAg was inhibited by chloroquin but not by brefeldin A. CONCLUSIONS: The findings indicate that processing and HLA class II-associated presentation of endogenously synthesized HBeAg in virus-infected cells, including hepatocytes, may occur. This mechanism may be involved in the regulation of the CD4(+) T-cell response to HBcAg/HBeAg.

Ageing and rheological properties of facial skin in women.

Ageing affects the mechanical properties of skin. Studies using objective measurements on facial skin have been rare and yielded contradictory information. In the present study, the age-related changes occurring in the mechanical properties of facial skin were reviewed using a computerized suction method. A total of 200 healthy women, aged from 17 to 68 years, were enrolled. Data show a significant increase in skin extensibility and a significant decline in elasticity with ageing. These changes become obvious in women approaching 40 years.

Pretreatment of skin with a Ginkgo biloba extract/sodium carboxymethyl-beta-1,3-glucan formulation appears to inhibit the elicitation of allergic contact dermatitis in man.

The clinical efficiency of mitigating contact dermatitis with a Ginkgo biloba extract and carboxymethyl-beta-1,3-glucan formulation was investigated in a double-blind versus placebo study using 22 subjects (Caucasian women aged 22-55 years) with allergic contact dermatitis from various substances in the European standard series. The formulation was applied to intact skin 2X a day for 2 weeks ("in use" application) prior to a single application of a selected contact allergen under a Finn Chamber for 24 h. Readings were carried out in a blind study by a dermatologist 2 and 3 days after patch removal. Representative photographs were taken of treated, placebo and untreated test areas. 68.2% of the panelists showed significantly reduced skin reactivity (p = 0.037*) on the treated site 2 days after patch removal, versus untreated and/or placebo sites. This finding indicates that the Ginkgo biloba/carboxymethyl-beta-1,3-glucan formulation can mitigate against allergic contact dermatitis.

New insight into the topical management of excessive sebum flow at the skin surface.

The sebum flow dynamics at the skin surface results from a multistep process starting with sebocyte proliferation, intracellular lipid synthesis, cell lysis in the sebaceous duct, storage of sebum in the follicular reservoir, discharge through the follicular opening and spreading over the stratum corneum. A handful of topical products may decrease the sebum output, most of them acting at the level of the follicular reservoir function. Among them, elubiol exhibits a clinically relevant effect on oily skin.

Tensile properties and contours of aging facial skin. A controlled double-blind comparative study of the effects of retinol, melibiose-lactose and their association.

BACKGROUND/AIMS: Facial aging is accompanied by modifications in the tensile properties and contours of skin. In the present study we instrumentally assessed and compared the effect of either 0.04% retinol (ROL), 1% melibiose and 4% lactose (ME-L) and their association (ROL-ME-L) to increase the firmness and smoothness of facial skin. A 1 % salicylic acid (SA) emulsion served as a cosmetic product reference. METHODS: A total of 120 women were allocated to four randomized groups of 30 subjects, each group receiving one of the test products or a combination of test products. The tensile properties of facial skin were measured using the Cutometer® on seven occasions during the 12-week treatment and during a 4-week post-treatment phase. Fine lines and wrinkles were assessed on replicas by using image analysis after optical shadowing. RESULTS: Significant differences in efficacy and lingering activity were observed between products. SA brought the weakest beneficial effects. ROL and ME-L provided better efficacy on both the tensile properties and contours of skin. They differed slightly according the nature of the biometrological variables. The combination ROL-ME-L achieved similar or even better results than the best of its components for each given physical property of skin. CONCLUSIONS: ROL, ME-L, and ROL-ME-L formulations improve physical properties of skin that are impaired by aging. Their activities are notably superior to those of a comparative SA formulation.

Pediatric medulloblastoma: radiation treatment technique and patterns of failure.

PURPOSE: In this study factors are analyzed that may potentially influence the site of failure in pediatric medulloblastoma. Patient-related, disease-related, and treatment-related variables are analyzed with a special focus on radiotherapy time-dose and technical factors. METHODS AND MATERIALS: Eighty-six children and adolescents with a diagnosis of medulloblastoma were treated in Switzerland during the period 1972-1991. Postoperative megavoltage radiotherapy was delivered to all patients. Simulation and portal films of the whole-brain irradiation (WBI) fields were retrospectively reviewed in 77 patients. The distance from the field margin to the cribiform plate and to the floor of the temporal fossa was carefully assessed and correlated with supratentorial failure-free survival. In 19 children the spine was treated with high-energy electron beams, the remainder with megavoltage photons. Simulation and port films of the posterior fossa fields were also reviewed in 72 patients. The field size and the field limits were evaluated and correlated with posterior fossa failure-free survival. RESULTS: In 36 patients (47%) the WBI margins were judged to miss the inferior portion of the frontal and temporal lobes. Twelve patients failed in the supratentorial region and 9 of these patients belonged to the group of 36 children in whom the inferior portion of the brain had been underdosed. On multivariate analysis only field correctness was retained as being significantly correlated with supratentorial failure-free survival (p = 0.049). Neither the total dose to the spinal theca nor the treatment technique (electron vs. photon beams) were significantly correlated with outcome. Posterior fossa failure-free survival was not influenced by total dose, overall treatment time, field size, or field margin correctness. Overall survival was not influenced by any of the radiotherapy-related technical factors. CONCLUSION: A correlation between WBI field correctness and supratentorial failure-free survival was observed. Treatment protocols should be considered that limit supratentorial irradiation mainly to subsites at highest risk of relapse. Optimized conformal therapy or proton beam therapy may help to reach this goal. Treating the spine with electron beams was not deletereous. A significant correlation between local control and other technical factors was not observed, including those relating to posterior fossa treatment. The use of small conformal tumor bed boost fields may be prefered to the larger posterior fossa fields usually considered as the standard treatment approach.

Recurrent mediastinal mass in a child with Hodgkin's disease following successful therapy: a diagnostic challenge.

The case of an 11-year-old girl with mediastinal stage III B-E Hodgkin's disease is described. She achieved complete remission with combined chemoradiotherapy according to the Swiss Pediatric Oncology Group-HD Protocol 1985. Six months after all therapy was stopped, a slowly growing retrosternal mass was detected. Computed tomography (CT) and gallium-67 single-photon emission CT (SPECT) could not elucidate the true origin of the tumor, nor did ultrasound-guided transthoracic fine-needle puncture. Open biopsy with histologic examination of the lesion has successfully identified the mass as thymic hyperplasia, a rebound immunologic reaction after chemoradiotherapy that mimicked tumor regrowth.

Low dose radiation for subfoveal choroidal neovascularization in age-related macular degeneration. A pilot study: radiotherapy for age-related macular degeneration.

The aim of our pilot study was to test the effect of low dose radiation on classic and occult subfoveal choroidal neovascularization (CNV) in age-related macular degeneration (AMD). The posterior pole of the afflicted eye of 12 patients was irradiated with 5 Gray (Gy), and that of 34 patients with 8 Gy. The radiotherapy was done by a linear accelerator (6 MV X-rays) during 4 consecutive days with daily doses of 1.25 Gy and 2 Gy respectively. At the time of treatment, and 6 weeks, 6 months and 1 year after, a simultaneous fluorescein and ICG angiography of both eyes were carried out, and the distance visual acuity was measured. In none of the cases were we able to note a reduction in the subfoveal membrane's size. With regards to the visual acuity, the evolution was slightly better than the spontaneous courses described in existing literature. Further prospective randomized studies with higher dose radiation are necessary in order to determine the significance of radiotherapy in the treatment of this pathology.

[Low dosage radiotherapy of subfoveal neovascularizations in age related macular degeneration. Results after 6 weeks and 6 months]. / Niedrig dosierte Radiotherapie der subfoveolären Neovaskularisationen bei altersabhängiger Makuladegeneration. Resultate nach 6 Wochen und 6 Monaten.

AIM OF THE STUDY: The aim of this pilot study is to test the effect of low dose radiation on classic and occult subfoveal neovascular membranes (SNVM) in age-related macular degeneration. METHODS AND PATIENTS: From November 1993 through to May 1995 the macula of the affected eye was irradiated with 5 Gy for 12 patients and with 8 Gy for 34 patients. The radiotherapy was done ambulatorily by a linear accelerator 6 MeV during 4 consecutive days with daily 1.25 Gy and 2 Gy respectively. A "half beam technic" was used to protect the lens. Before the treatment, 6 weeks and 6 months later different parameters of the visual acuity were measured and a simultaneous Fluo- and ICG-angiography was done. RESULTS: In the 5 Gy group, all the planned controls were done for 11 patients. 9 membranes were classic and 2 occult. After 6 months the vision in the distance remained the same in 7 cases, was better in 2 cases and worse in 2 cases. The size of the membrane increased in 10 cases and remained unchanged in 1 case. In the 8 Gy group, all the planned controls were done for 29 patients. 12 membranes were classic and 17 occult. The vision in the distance remained the same in 17 cases, was better in 4 cases and worse in 8 cases. The size of the membrane increased in 12 cases and there was no change in 17 cases. DISCUSSION AND CONCLUSION: Exact comparisons between the 5 Gy and 8 Gy group are not possible because of the different composition of these groups. In no case were we able to note a reduction of the size of the membrane. Concerning the visual acuity, our results are better than the spontaneous evolutions described in the literature. Meanwhile, affirmations about possible stabilisation of the visual acuity are too early. A further study which is being done in our hospital may possibly bring new information.

[Radiotherapy of hypophyseal adenoma]. / Strahlentherapie der Hypophysenadenome.

The efficacy of radiotherapy alone for control of pituitary adenoma is well documented. Because of slow endocrinologic response and delayed shrinkage of the tumor, it is reserved for inoperable patients. Transsphenoidal surgery is generally regarded as the treatment of choice. It provides prompt reduction of tumor mass and hormone levels. Radiotherapy as an adjunct has been proven effective in gross residual disease and for post-operatively elevated hormone levels. It is also effective in treating recurrencies after surgery. Its value in an interdisciplinary approach is discussed.

[Low dosage radiotherapy of subfoveal neovascularization in age-related macular degeneration. Preliminary results]. / Niedrig dosierte Radiotherapie der subfoveolären Neovaskularisationen bei altersabhängiger Makuladegeneration. Vorläufige Resultate.

AIM OF THE STUDY: The aim of this study is to test the effect of low dose radiation on the subfoveal neovascular membranes (SNVM) and to analyse visual acuity in age-related macular degeneration. METHODS AND PATIENTS: From November 1993 through to August 1994, 10 patients, on the one hand, were given a dose of 5 Gy followed by controls 6 weeks and 6 months later. On the other hand, 21 patients were treated with a dose of 8 Gy and were subjected to controls 6 weeks later. Before the radiotherapy and during the control sessions, all patients were required to be measured for different parameters of visual acuity and to receive a simultaneous fluorescein and indocyanine green angiography. The radiotherapy was done by a linear accelerator 6 MeV and through a lateral port 3 x 4 cm in half beam technic. RESULTS: In the 5 Gy group, no changes in the parameters for visual acuity were noted in most cases after 6 months. In 9 of the cases, the membranes had increased in size and in 1 case, they had remained unchanged. In the 8 Gy group, no changes in the visual acuity or in the membrane size were diagnosed. Of all the patients treated, only one refused the angiography control. DISCUSSION AND CONCLUSIONS: Given the low dose used and the period of observation, the visual acuity of all patients remained stable. The size of the membranes increased in most cases for those 5 Gy patients and in this respect, no changes at all were noted in the 8 Gy patients. In order to better evaluate the potential of radiotherapy, this study must be pursued and coupled with further studies analysing the effect of different doses on patients.

Prognosis of human chorionic gonadotropin-producing seminoma treated by postoperative radiotherapy.

PURPOSE: To clarify the controversy about the management and prognosis of human chorionic gonadotropin-producing seminoma, the records of 132 patients with abnormal human chorionic gonadotropin values treated with radiotherapy were analyzed. METHODS AND MATERIALS: The records of 1169 patients with pure seminoma treated in 10 institutions were screened for serum or urinary human chorionic gonadotropin. One hundred and thirty two patients with elevated human chorionic gonadotropin were found: 96 Stage I, 20 IIA, 7 IIB, 8 III and 1 IV. Median age was 34 y., mean follow-up was 5.0 years [range 1-12 y]. All received infradiaphragmatic radiotherapy (median dose 30 Gy), 25 (2 Stage I, 11 IIA, 5 IIB and 7 III) supradiaphragmatic radiotherapy (median dose: 28.5 Gy) and 10 had also initial chemotherapy (3 Stage IIB 6 III and 1 IV). Patients were allocated to three groups according to human chorionic gonadotropin values: (a) moderate elevation: up to 10 times (104 pts), (b) high elevation: 10 to 100 times (20 pts), (c) very high elevation: over 100 times the upper limit of normal value (8 pts). RESULTS: The proportion of Stage I, II and III was 76%, 19%, 5% in the ME group versus 50%, 35%, 15% in the high elevation group (p < 0.05). In the very high elevation group there were 7 Stage I and 1 Stage IV. Of 132 patients, six died (three dead of disease, two suicides, one acquired immunodeficiency syndrome). The 5 years overall survival probability was 94%. There were seven recurrences (initial stage: 1 Stage I, 2 IIB, 3 III and 1 IV). Of these, there were one in-field recurrence, 3 out of field and 3 in both sites. In 5 of 7, the human chorionic gonadotrophin level was again elevated at recurrence. The 5 years recurrence-free-survival probability was 94% (98% for Stage I, 100% for Stage IIA and 65% for Stage IIB and III [p < 0.001 between I and IIB + III, p < 0.05 between IIA and IIB + III]). Four of the 7 recurrences were salvaged by chimiotherapy +/- radiotherapy. In the high elevation and very high elevation groups, the 5 years recurrence-free-survival was 88%, vs. 96% for the moderate elevation group (p = 0.10). CONCLUSION: Based on this series of patients, human chorionic gonadotropin production is not an unfavorable prognostic factor in pure seminoma. Even in the subgroups with high or very high human chorionic gonadotropin levels (who had a higher proportion of advanced stages), the prognosis remained excellent. In Stage I and IIA seminoma with abnormal human chorionic gonadotropin levels, recurrence rate after post-operative radiotherapy alone is extremely low.