Search

Objective. To evaluate feasibility of chemoradiation as alternative for extensive surgery in patients with locally advanced vulvar cancer and to report on locoregional control, toxicity and survival. Methods. In a multicenter, prospective phase II trial patients with locally advanced vulvar cancer were treated with locoregional radiotherapy combined with sensitizing chemotherapy (capecitabine). Treatment feasibility, percentage locoregional control, survival and toxicity were evaluated. Results. 52 patients with mainly T2/T3 disease were treated according to the study protocol in 10 centers in the Netherlands from 2007 to 2019. Full dose radiotherapy (tumor dose of 64.8Gy) was delivered in 92% and full dose capecitabine in 69% of patients. Most prevalent acute >_ grade 3 toxicities were regarding skin/ mucosa and pain (54% and 37%). Late >_grade 3 toxicity was reported for skin/mucosa (10%), fibrosis (4%), GI incontinence (4%) and stress fracture or osteoradionecrosis (4%). Twelve weeks after treatment, local clinical complete response (cCR) and regional control (RC) rates were 62% and 75%, respectively. After 2 years, local cCR persisted in 22 patients (42%) and RC was 58%. Thirty patients (58%) had no evidence of disease at end of follow-up (median 35 months). In 9 patients (17%) extensive surgery with stoma formation was needed. Progression free survival was 58%, 51% and 45% and overall survival was 76%, 66%, 52% at 1,2, and 5 years. Conclusions. Definitive capecitabine-based chemoradiation as alternative for extensive surgery is feasible in locally advanced vulvar cancer and results in considerable locoregional control with acceptable survival rates with manageable acute and late toxicity. (c) 2021 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http:// creativecommons.org/licenses/by-nc-nd/4.0/).

Background. Decision making regarding adjuvant therapy for high-risk endometrial cancer is complex. The aim of this study was to determine patients' and clinicians' minimally desired survival benefit to choose chemoradiotherapy over radiotherapy alone. Moreover, influencing factors and importance of positive and negative treatment effects (i.e. attribute) were investigated.Methods. Patients with high-risk endometrial cancer treated with adjuvant pelvic radiotherapy with or without chemotherapy and multidisciplinary gynaecologic oncology clinicians completed a trade-off questionnaire based on PORTEC-3 trial data.Results. In total, 171 patients and 63 clinicians completed the questionnaire. Median minimally desired benefit to make chemoradiotherapy worthwhile was significantly higher for patients versus clinicians (10% vs 5%, p = 0.02). Both patients and clinicians rated survival benefit most important during decision making, followed by long-term symptoms. Older patients (OR 0.92 [95%CI 0.87 & ndash;0.97]; p = 0.003) with comorbidity (OR 0.34 [95% CI 0.12 & ndash;0.89]; p = 0.035) had lower preference for chemoradiotherapy, while patients with better numeracy skills (OR 1.2 [95%CI 1.05 & ndash;1.36], p = 0.011) and chemoradiotherapy history (OR 25.0 [95%CI 8.8 & ndash;91.7]; p < 0.001) had higher preference for chemoradiotherapy.& nbsp;Conclusions. There is a considerable difference in minimally desired survival benefit of chemoradiotherapy in high-risk endometrial cancer among and between patients and clinicians. Overall, endometrial cancer patients needed higher benefits than clinicians before preferring chemoradiotherapy.(c) 2021 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http:// creativecommons.org/licenses/by/4.0/).

BackgroundVaginal brachytherapy is currently recommended as adjuvant treatment in patients with high-intermediate risk endometrial cancer to maximize local control and has only mild side effects and no or limited impact on quality of life. However, there is still considerable overtreatment and also some undertreatment, which may be reduced by tailoring adjuvant treatment to the patients’ risk of recurrence based on molecular tumor characteristics.Primary objectivesTo compare the rates of vaginal recurrence in women with high-intermediate risk endometrial cancer, treated after surgery with molecular-integrated risk profile-based recommendations for either observation, vaginal brachytherapy or external pelvic beam radiotherapy or with standard adjuvant vaginal brachytherapyStudy hypothesisAdjuvant treatment based on a molecular-integrated risk profile provides similar local control and recurrence-free survival as current standard adjuvant brachytherapy in patients with high-intermediate risk endometrial cancer, while sparing many patients the morbidity of adjuvant treatment and reducing healthcare costs.Trial designA multicenter, international phase III randomized trial (2:1) of molecular-integrated risk profile-based adjuvant treatment (experimental arm) or adjuvant vaginal brachytherapy (standard arm).Major inclusion/exclusion criteriaWomen aged 18 years and over with a histological diagnosis of high-intermediate risk endometrioid endometrial cancer after total abdominal or laparoscopic hysterectomy and bilateral salpingo-oophorectomy. High-intermediate risk factors are defined as: (i) International Federation of Gynecology and Obstetrics stage IA (with invasion) and grade 3; (ii) stage IB grade 1 or 2 with age ≥60 and/or lymph-vascular space invasion; (iii) stage IB, grade 3 without lymph-vascular space invasion; or (iv) stage II (microscopic and grade 1).EndpointsThe primary endpoint is vaginal recurrence. Secondary endpoints are recurrence-free and overall survival; pelvic and distant recurrence; 5-year vaginal control (including treatment for relapse); adverse events and patient-reported symptoms and quality of life; and endometrial cancer-related healthcare costs.Sample size500 eligible and evaluable patients.Estimated dates for completing accrual and presenting resultsEstimated date for completing accrual will be late 2021. Estimated date for presentation of (first) results is expected in 2023.Trial registrationThe trial is registered at clinicaltrials.gov (NCT03469674) and ISRCTN (11659025).

Background and purpose: Patients with advanced cancer may develop painful bone metastases, potentially resulting in pathological fractures. Adequate fracture risk assessment is of key importance to prevent fracturing and maintain mobility. This study aims to validate the clinical reliability of axial cortical involvement with a 30 mm threshold on conventional radiographs to assess fracture risk in femoral bone metastases.Materials and methods: All patients with bone metastases who received radiotherapy for pain included in two multicentre prospective studies were selected. Conventional radiographs obtained at a maximum of two months prior to radiotherapy were collected. Three experts independently measured lesions and scored radiographic characteristics. Sensitivity, specificity, positive (PPV) and negative predictive value (NPV) were calculated.Results: Hundred patients were included with a median follow-up of 23.0 months (95%CI: 10.6-35.5). Two fractures occurred in lesions with axial cortical involvement = 30 mm. Sensitivity, specificity, PPV and NPV of axial cortical involvement for predicting femoral fractures were 86%, 50%, 20% and 96%, respectively. Patients with lesions >= 30 mm had a 5.3 times higher fracture risk than patients with smaller lesions.Conclusion: Our validation study confirmed the use of 30 mm axial cortical involvement to assess fracture risk in femoral bone metastases. Until a more accurate and practically feasible method has been developed, this clinical parameter remains an easy method to assess femoral fracture risk to aid patients and clinicians to choose the optimal individual treatment modality. (C) 2019 Elsevier B.V. All rights reserved.

BACKGROUND:The PORTEC-3 trial investigated the benefit of combined adjuvant chemotherapy and radiotherapy versus pelvic radiotherapy alone for women with high-risk endometrial cancer. We updated the analysis to investigate patterns of recurrence and did a post-hoc survival analysis.METHODS:In the multicentre randomised phase 3 PORTEC-3 trial, women with high-risk endometrial cancer were eligible if they had International Federation of Gynaecology and Obstetrics (FIGO) 2009 stage I, endometrioid grade 3 cancer with deep myometrial invasion or lymphovascular space invasion, or both; stage II or III disease; or stage I-III disease with serous or clear cell histology; were aged 18 years and older; and had a WHO performance status of 0-2. Participants were randomly assigned (1:1) to receive radiotherapy alone (48·6 Gy in 1·8 Gy fractions given on 5 days per week) or chemoradiotherapy (two cycles of cisplatin 50 mg/m2 given intravenously during radiotherapy, followed by four cycles of carboplatin AUC5 and paclitaxel 175 mg/m2 given intravenously), by use of a biased coin minimisation procedure with stratification for participating centre, lymphadenectomy, stage, and histological type. The co-primary endpoints were overall survival and failure-free survival. Secondary endpoints of vaginal, pelvic, and distant recurrence were analysed according to the first site of recurrence. Survival endpoints were analysed by intention-to-treat, and adjusted for stratification factors. Competing risk methods were used for failure-free survival and recurrence. We did a post-hoc analysis to analyse patterns of recurrence with 1 additional year of follow-up. The study was closed on Dec 20, 2013; follow-up is ongoing. This study is registered with ISRCTN, number ISRCTN14387080, and ClinicalTrials.gov, number NCT00411138.FINDINGS:Between Nov 23, 2006, and Dec 20, 2013, 686 women were enrolled, of whom 660 were eligible and evaluable (330 in the chemoradiotherapy group, and 330 in the radiotherapy-alone group). At a median follow-up of 72·6 months (IQR 59·9-85·6), 5-year overall survival was 81·4% (95% CI 77·2-85·8) with chemoradiotherapy versus 76·1% (71·6-80·9) with radiotherapy alone (adjusted hazard ratio [HR] 0·70 [95% CI 0·51-0·97], p=0·034), and 5-year failure-free survival was 76·5% (95% CI 71·5-80·7) versus 69·1% (63·8-73·8; HR 0·70 [0·52-0·94], p=0·016). Distant metastases were the first site of recurrence in most patients with a relapse, occurring in 78 of 330 women (5-year probability 21·4%; 95% CI 17·3-26·3) in the chemoradiotherapy group versus 98 of 330 (5-year probability 29·1%; 24·4-34·3) in the radiotherapy-alone group (HR 0·74 [95% CI 0·55-0·99]; p=0·047). Isolated vaginal recurrence was the first site of recurrence in one patient (0·3%; 95% CI 0·0-2·1) in both groups (HR 0·99 [95% CI 0·06-15·90]; p=0·99), and isolated pelvic recurrence was the first site of recurrence in three women (0·9% [95% CI 0·3-2·8]) in the chemoradiotherapy group versus four (0·9% [95% CI 0·3-2·8]) in the radiotherapy-alone group (HR 0·75 [95% CI 0·17-3·33]; p=0·71). At 5 years, only one grade 4 adverse event (ileus or obstruction) was reported (in the chemoradiotherapy group). At 5 years, reported grade 3 adverse events did not differ significantly between the two groups, occurring in 16 (8%) of 201 women in the chemoradiotherapy group versus ten (5%) of 187 in the radiotherapy-alone group (p=0·24). The most common grade 3 adverse event was hypertension (in four [2%] women in both groups). At 5 years, grade 2 or worse adverse events were reported in 76 (38%) of 201 women in the chemoradiotherapy group versus 43 (23%) of 187 in the radiotherapy-alone group (p=0·002). Sensory neuropathy persisted more often after chemoradiotherapy than after radiotherapy alone, with 5-year rates of grade 2 or worse neuropathy of 6% (13 of 201 women) versus 0% (0 of 187). No treatment-related deaths were reported.INTERPRETATION:This updated analysis shows significantly improved overall survival and failure-free survival with chemoradiotherapy versus radiotherapy alone. This treatment schedule should be discussed and recommended, especially for women with stage III or serous cancers, or both, as part of shared decision making between doctors and patients. Follow-up is ongoing to evaluate long-term survival.FUNDING:Dutch Cancer Society, Cancer Research UK, National Health and Medical Research Council, Project Grant, Cancer Australia Grant, Italian Medicines Agency, and the Canadian Cancer Society Research Institute.

Contains fulltext : 229838.pdf (Publisher’s version ) (Open Access) OBJECTIVE: The PORTEC-4a trial investigates molecular-integrated risk profile guided adjuvant treatment for endometrial cancer. The quality assurance programme included a dummy run for vaginal brachytherapy prior to site activation, and annual quality assurance to verify protocol adherence. Aims of this study were to evaluate vaginal brachytherapy quality and protocol adherence. METHODS: For the dummy run, institutes were invited to create a brachytherapy plan on a provided CT-scan with the applicator in situ. For annual quality assurance, institutes provided data of one randomly selected brachytherapy case. A brachytherapy panel reviewed and scored the brachytherapy plans according to a checklist. RESULTS: At the dummy run, 15 out of 21 (71.4%) institutes needed adjustments of delineation or planning. After adjustments, the mean dose at the vaginal apex (protocol: 100%; 7 Gy) decreased from 100.7% to 99.9% and range and standard deviation (SD) narrowed from 83.6-135.1 to 96.4-101.4 and 8.8 to 1.1, respectively. At annual quality assurance, 22 out of 27 (81.5%) cases had no or minor and 5 out of 27 (18.5%) major deviations. Most deviations were related to delineation, mean dose at the vaginal apex (98.0%, 74.7-114.2, SD 7.6) or reference volume length. CONCLUSIONS: Most feedback during the brachytherapy quality assurance procedure of the PORTEC-4a trial was related to delineation, dose at the vaginal apex and the reference volume length. Annual quality assurance is essential to promote protocol compliance, ensuring high quality vaginal brachytherapy in all participating institutes.

Objectives In this prospective cohort study, we investigated whether patient-specific finite element (FE) models can identify patients at risk of a pathological femoral fracture resulting from metastatic bone disease, and compared these FE predictions with clinical assessments by experienced clinicians. Methods A total of 39 patients with non-fractured femoral metastatic lesions who were irradiated for pain were included from three radiotherapy institutes. During follow-up, nine pathological fractures occurred in seven patients. Quantitative CT-based FE models were generated for all patients. Femoral failure load was calculated and compared between the fractured and non-fractured femurs. Due to inter-scanner differences, patients were analyzed separately for the three institutes. In addition, the FE-based predictions were compared with fracture risk assessments by experienced clinicians. Results In institute 1, median failure load was significantly lower for patients who sustained a fracture than for patients with no fractures. In institutes 2 and 3, the number of patients with a fracture was too low to make a clear distinction. Fracture locations were well predicted by the FE model when compared with post-fracture radiographs. The FE model was more accurate in identifying patients with a high fracture risk compared with experienced clinicians, with a sensitivity of 89% versus 0% to 33% for clinical assessments. Specificity was 79% for the FE models versus 84% to 95% for clinical assessments. Conclusion FE models can be a valuable tool to improve clinical fracture risk predictions in metastatic bone disease. Future work in a larger patient population should confirm the higher predictive power of FE models compared with current clinical guidelines. Cite this article: F. Eggermont, L. C. Derikx, N. Verdonschot, I. C. M. van der Geest, M. A. A. de Jong, A. Snyers, Y. M. van der Linden, E. Tanck. Can patient-specific finite element models better predict fractures in metastatic bone disease than experienced clinicians? Towards computational modelling in daily clinical practice. Bone Joint Res 2018;7:430–439. DOI: 10.1302/2046-3758.76.BJR-2017-0325.R2.

Aim: The aim of this study is to examine possible associations between the transfusion of RBC or platelets (PLTs) and the development of retinopathy of prematurity (ROP) in infants. Methods: This retrospective, national, case-control study included all live births in Switzerland between 2013 and 2018. We investigated preterm infants at a gestational age of n = 178). Each case infant was matched to another of the same sex who did not develop ROP (n = 178, control group). Results: When compared with the control group, we observed higher numbers of RBC transfusions per infant and higher percentages of infants receiving PLT transfusions in the case group. An adjusted logistic regression analysis revealed that both RBC (odds ratio [OR] 1.081, 95% confidence interval [CI] 1.020–1.146) and PLT transfusions (OR = 2.502, 95% CI 1.566–3.998) numbers were associated with ROP development. Conclusions: Multiple RBC and PLT transfusions are associated with higher stage ROP development. Prospective studies are required to determine their potential as risk factors.

Objective To evaluate the value of cervical biopsies 12 to 16 weeks post chemoradiation (CRT) in patients with locally advanced cervical cancer (LACC), to identify patients eligible for salvage surgery. Methods We retrospectively collected data of 154 patients with LACC, who received chemoradiation as primary treatment between 1998 and 2015 at the Radboud university medical center in Nijmegen (Radboud). In patients eligible for salvage surgery, without suspicious lymph nodes on imaging, a cervical biopsy was taken post CRT under general anesthesia to evaluate whether complete clinical remission was obtained. We analyzed data from 78 patients with cervical biopsy post CRT and 60 patients without cervical biopsy. Follow-up, biopsy results, patient characteristics and subsequent treatment modalities were reviewed. Results In total, 154 patients with LACC received CRT. The median follow up time was 30.5 months. Sixteen patients (10.4%) were lost to follow up. Of the remaining 138 women, 78 patients underwent a cervical biopsy post CRT. Eight out of the 78 patients (10.3%) had residual disease after CRT, six of these patients underwent salvage surgery, with long-term complete remission in 4 of these patients (66.7%). Conclusion Post CRT cervical biopsy in locally advanced cervical cancer patients was beneficial in 4 out of 78 patients (5%). As 1 in 20 patients will achieve long-term survival by salvage hysterectomy, taking a cervical biopsy 16 weeks post radiation seems thus advisable.

Previously, we showed that case-specific non-linear finite element (FE) models are better at predicting the load to failure of metastatic femora than experienced clinicians. In this study we improved our FE modelling and increased the number of femora and characteristics of the lesions. We retested the robustness of the FE predictions and assessed why clinicians have difficulty in estimating the load to failure of metastatic femora. A total of 20 femora with and without artificial metastases were mechanically loaded until failure. These experiments were simulated using case-specific FE models. Six clinicians ranked the femora on load to failure and reported their ranking strategies. The experimental load to failure for intact and metastatic femora was well predicted by the FE models (R2= 0.90 and R2= 0.93, respectively). Ranking metastatic femora on load to failure was well performed by the FE models (τ = 0.87), but not by the clinicians (0.11 < τ < 0.42). Both the FE models and the clinicians allowed for the characteristics of the lesions, but only the FE models incorporated the initial bone strength, which is essential for accurately predicting the risk of fracture. Accurate prediction of the risk of fracture should be made possible for clinicians by further developing FE models.

PURPOSE: To report a new family with Blau syndrome caused by CARD15/NOD2 mutation. DESIGN: Observational case series. METHODS: Detailed clinical evaluation in three affected relatives with Blau syndrome. Haplotype and mutation analysis of the CARD15/NOD2 gene were performed. RESULTS: Ocular manifestations identified in the proband include bilateral band keratopathy, cataract, iritis, vitritis and severe granulomatous choroidopathy. The mother and one brother of the proband exhibit the same characteristic organ involvements of this disease. Haplotype analysis from the pericentromeric region on chromosome 16 identified a common haplotype in all affected relatives that is absent in unaffected relatives. Sequencing analysis revealed a heterozygous pathogenic mutation in the CARD15/NOD2 gene, the previously reported p.R334W substitution. CONCLUSION: Blau syndrome is a rare autosomal-dominant disease that can lead to severe visual impairment. The search of a CARD15/NOD2 mutation could be helpful in the differential diagnosis of childhood uveitis.

We report the case of an immunocompetent 78-year-old woman who developed cytomegalovirus (CMV) retinitis after a single intravitreous injection of triamcinolone acetonide (IVTA). Review of medical records. The patient with macular edema secondary to branch retinal vein occlusion developed peripheral retinitis with hemorrhagic and inflammatory vascular sheathing 3 months after IVTA. A presumptive diagnosis of viral retinitis was confirmed by polymerase chain reaction (PCR) of the aqueous humor tap. The PCR test was positive for CMV DNA. The patient slowly responded to intravenous ganciclovir and oral valganciclovir. After therapeutic vitrectomy for intercurrent vitreous hemorrhage, and while still under treatment, the retinitis resolved completely with final visual acuity of 20/25. CMV retinitis can occur after local immunosuppression with IVTA in an immunocompetent patient with no other systemic risk factors.

Purpose: To study the prevalence of polypoidal choroidal vasculopathy (PCV) in Caucasian patients with occult choroidal neovascularization (CNV); to study the clinical spectrum of PCV in Caucasians and the outcome after laser photocoagulation of such lesions. Methods: (1) A consecutive series of 374 eyes of Caucasian patients at least 58 years old, presenting occult CNV, presumed to have age-related macular degeneration (AMD) on fluorescein angiography (FA) were further characterized by indocyanine green angiography (ICGA) to determine the frequency of PCV. (2) The funduscopic, FA and ICGA findings in a cohort of 36 Caucasian patients with PCV were analyzed. (3) The outcome after laser photocoagulation was studied in 14 PCV eyes with a minimum follow-up of 6 months. Results: (1) Fourteen of 374 eyes (4%) presenting occult CNV in patients at least 58 years old were diagnosed as PCV by means of ICG-A. (2) A polypoidal lesion was found in the macula in 22 of 45 PCV eyes, in the peripapillary area in 16 of 45, under the temporal vascular arcade in 6 of 45 and in the midperiphery in 6 of 45. Large or soft drusen were observed in 15 of 45 eyes with PCV. (3) Regression of fundus signs without persisting polyps 6 months after laser photocoagulation was obtained in 5 of 5 treated peripapillary lesions but in only 5 of 9 treated macular or arcade lesions. Conclusion: Polypoidal choroidal vasculopathy is not rare in Caucasian patients presenting with occult choroidal neovascularization. The fundus abnormalities seen in such eyes overlap with the typical manifestations of AMD. Whereas the prognosis after photocoagulation of peripapillary polypoidal lesions appears to be relatively good, it is more guarded for macular or arcade lesions.

This paper presents an unified overview of a new family of distributed algortithms for routing and load balancing in dynamic communication networks. These new algorithms are described as an extension to the classical routing algorithms: they combine the ideas of online asynchronous distance vector routing with adaptive link state routing. Estimates of the current traffic condition and link costs are measured by sending routing agents in the network that mix with the regular information packets and keep track of the costs (e.g. delay) encountered during their journey. The routing tables are then regularly updated based on that information without any central control nor complete knowledge of the network topology. Two new algorithms are proposed here. The first one is based on round trip routing agents that update the routing tables by backtracking their way after having reached the destination. The second one relies on forward agents that update the routing tables directly as they move toward their destination. An efficient co-operative scheme is proposed to deal with asymmetric connections. All these methods are compared on a simulated network with various traffic loads; the robustness of the new algorithms to network changes is proved on various dynamic scenarii.

AIMS/BACKGROUND--This study was undertaken to confirm the association between diffuse retinal pigment epitheliopathy (DRPE) and systemic corticosteroid therapy. This finding can be of help in determining an aetiological factor in DRPE and associated diseases. Corticosteroids may contribute to the development of leakage in the presence of a retinal pigment epitheliopathy or central serous chorioretinopathy. METHODS--Cases of DRPE were collected from the files of members of the European Fluorescein Angiography Club. There were 34 who developed their ophthalmic symptoms while being treated with corticosteroids. RESULTS--DRPE developed in 34 patients from 10 European eye clinics during systemic treatment with corticosteroids. Thirteen patients were treated with corticosteroids after allotransplantation, 21 other patients developed ocular symptoms while treated with steroids for serious systemic disorders. Symptoms occurred in some patients when the daily corticosteroid dosage was elevated, and the visual complaints ameliorated or even disappeared sometimes on discontinuation of the corticosteroid therapy. CONCLUSION--Corticosteroids can damage the retinal pigment epithelial barrier and predispose a patient to serous retinal detachment, whereas psychological stress may play a role in the development of central serous chorioretinopathy. A decrease of the daily corticosteroid dosage may help to diminish the visual symptoms.

We report a case of bilateral optic neuropathy associated with the CREST syndrome, a variant of scleroderma. Immunosuppressive therapy achieved significant improvement of the visual symptoms for two years. The pathophysiological mechanisms underlying this unique association remain unclear.

Contains fulltext : 79904.pdf (Publisher’s version ) (Closed access) PURPOSE: To evaluate the long-term outcome after surgery and radiotherapy for patients with sinonasal cancer and assess late toxicity, with special emphasis on hypothalamic-pituitary dysfunction. METHODS AND MATERIALS: A retrospective analysis of 168 patients treated for sinonasal cancer in a single institute between 1986 and 2006. A more detailed analysis was performed on a subgroup of 76 patients with adenocarcinoma or squamous cell carcinoma treated with curative intent. Long-term survivors were evaluated for late toxicity by a multidisciplinary team using the late effects of normal tissues (LENT SOMA) scoring system. Additional endocrinologic tests were performed for assessment of hypothalamic-pituitary function. RESULTS: Five-year actuarial local control and overall survival rates were 62% and 35% for all patients and 64% and 42% for the subgroup with squamous cell carcinoma and adenocarcinoma. In multivariate analysis, T stage was the only significant factor predicting local relapse (79% at 5 years for T1-T3 vs. 53% for T4; p = 0.006). Sinonasal mucosal melanomas had the highest rate of regional failure (33% at 5 years). Thirteen of 21 patients (62%) evaluated at the late morbidity clinic had hormonal disturbances, of whom 5 (24%) had definitive evidence of hypopituitarism with multiple hormonal deficiencies. CONCLUSION: Local failure is the dominant cause of treatment failure for patients with sinonasal cancer, with T4 stage the only independent predictor. Because of a high rate of radiation-induced hypopituitarism, we recommend endocrinologic surveillance for these patients.

Specific fundus changes have been reported in patients with membranoproliferative glomerulonephritis type II (MPGN type II). We studied the clinical course of this retinopathy in four patients who all had a long follow-up with several fundus examinations. Sequential observation was indicative of a slow progression of the retinopathy. Most eyes maintained in the chronic stages a nearly normal visual acuity, and a full visual field despite the existence of marked drusen and atrophic changes. The prognosis however must be somewhat guarded, since choroidal neovascularization developed in three eyes and caused bilateral severe visual loss in one patient.

Three patients with systemic lupus erythematosus (SLE) associated with anti-phospholipid antibodies are reported. All three had severe vaso-occlusive disease: the first had an unilateral vaso-occlusive retinopathy, the second an unilateral central retinal venous obstruction, and the third a bilateral ischemic choroidopathy. The association of these occlusive ocular vascular diseases with the presence of the lupus anticoagulant and other associated factors in SLE is discussed.

PURPOSE: To report the clinical and imaging features in four male patients presenting with Susac syndrome, a microangiopathy affecting the brain, the retina, and the cochlea. METHODS: Retrospective review of clinical data, fluorescein angiograms, and magnetic resonance imaging findings in these four cases. RESULTS: All four patients were young men (range, 20-35 years). The axiomatic triad of ocular, cochlear, and neurologic involvement was present in three patients. Neurologic symptoms were absent in the fourth one. Fluorescein angiography showed arteriolar wall hyperfluorescence in all four patients. Magnetic resonance images showed in three patients multifocal hyperintense lesions in the white matter and the corpus callosum with typical involvement of the central fibers. Therapeutic modalities and clinical course are described. Three patients had a follow-up of 3, 5, and 13 years with complete remission of the disease within 1 year in all three cases. One patient had severe neuropsychological sequelae. CONCLUSION: Susac syndrome seems to be less unusual in men than previously reported. Though presenting as a self-limited monophasic course disease in most cases, it may result in severe neuropsychological sequelae. Early diagnosis of the syndrome is enabled by the combination of the ophthalmologic, audiometric, and brain magnetic resonance features.

Purpose : To evaluate the safety and efficacy of photodynamic therapy with verteporfin (PDT) for subfoveal classic choroidal neovascularization (CNV) related to punctate inner choroidopathy (PIC) or presumed ocular histoplasmosis-like syndrome (POHS-like). Methods : Retrospective review of 16 eyes from 14 patients with subfoveal classic CNV associated with PIC or POHS-like and treated with PDT. Results : The mean visual acuity increased from 4.5/10 (range: 1/10-9/10) to 7/10 (range: 2/10-10/10) after a mean follow-up of 21 months (range: 8-32 months) and a mean number of 2 PDT (range: 1-6). Visual acuity remained stable or improved in 13 of the 16 eyes (81%) and decreased in three. Conclusion : This nearly two-year follow-up study suggests that PDT could be helpful for patients with subfoveal classic CNV related to PIC or POHS-like.

PURPOSE: To evaluate the effect of photodynamic therapy on subfoveal neovascular membrane related to type 2A idiopathic juxtafoveolar retinal telangiectasia. DESIGN: Interventional case series. METHODS: Retrospective review of four eyes of four patients who underwent photodynamic therapy for subfoveal neovascular membrane secondary to idiopathic juxtafoveolar retinal telangiectasia. Ocular photodynamic therapy with verteporfin was performed in all cases using standard protocols. Results are given in terms of final visual acuity and neovascular membrane activity based on clinical examination, fluorescein and indocyanin green angiography, and, in two cases, optical coherence tomography. RESULTS: Baseline visual acuity of 20/30 and 20/40 (x2) was maintained in three patients after one, two, and three sessions of photodynamic therapy respectively, and a follow-up of 23, 21, and 9 months. Leakage specific to the subfoveal neovascular membrane ceased on the fluorescein angiography. In the other patient, the final vision decreased from 20/50 to 20/200 after four sessions of photodynamic therapy and a follow-up of 14 months. Although there was still mild persistent leakage on the fluorescein angiography, neovascular membrane size was unchanged, and no subretinal fluid was demonstrated on optical coherence tomography. CONCLUSIONS: Data from this case series suggest that photodynamic therapy may be effective in managing subfoveal neovascular membrane associated with idiopathic juxtafoveolar retinal telangiectasia, which usually carries a poor visual prognosis. Prospective study is required to confirm the beneficial effect of this treatment.

We report on four patients, from three different families, with Senior-Loken syndrome (SLS). They were unusual in that they reached end-stage renal failure (ESRF) only during the fifth or sixth decade. SLS is an autosomal-recessive disorder defined by the association of nephronophthisis and retinal dystrophy. Affected individuals invariably progress to ESRF, usually before the age of 20 years. The diagnosis was based on typical clinical presentation and characteristic renal histology, that is, a picture of chronic interstitial nephritis with pronounced thickening and multilayering of tubular basement membranes. Deterioration of renal function was slow, leading to ESRF between the ages of 42 and 56 years. Retinal dystrophy, already symptomatic during childhood in two patients, led to severe visual impairment in all. In contrast with four cases of SLS recently reported in very young patients, the NPH1 gene (the main gene responsible for nephronophthisis) was not deleted in our two tested patients. We conclude that SLS should be considered in adults who suffer from both chronic interstitial nephropathy and retinal degeneration. Whether the SLS is a variant of nephronophthisis and whether early- and late-onset renal failure in SLS is accounted for by genetic or allelic heterogeneity remain to be determined.

A simple model of multi-agent three-dimensional construction is presented. The properties of this model are investigated. Based on these properties, a fitness function is defined to characterize the structured patterns that can be generated by the model. The fitness function assigns a value to each pattern. The choice of the fitness function is validated by the fact that human observers tend to view patterns with high (resp. low) fitness as structured (resp. unstructured). A genetic algorithm based on this fitness function is used to explore the space of possible patterns. The genetic algorithm is able to make use of sub-modules of existing patterns and recombine them to produce novel patterns, but strong epistatic interactions among genes make the fitness landscape rugged and prevent more complex patterns from being produced.

A high-grade diffuse T cell lymphoma, initially simulating bilateral panuveitis, was diagnosed by analysis of a vitreous biopsy specimen and a breast tumor in a 57-year-old woman. It responded favorably to aggressive chemotherapy before it relapsed in leukemic transformation. This case emphasizes the misleading initial symptoms of primary intraocular lymphoma and the role of immunophenotyping in the diagnosis and classification of lymphoproliferative ocular disorders. The presentation and management of uveal lymphoid neoplasia are discussed.

A simple mechanism is presented, based on ant-like agents, for routing and load balancing in telecommunications networks, following the initial works of Appleby and Stewart [1] and Schoonderwoerd et al. [32,33]. In the present work, agents are very similar to those proposed by Schoonderwoerd et al. [32,33], but are supplemented with the ability to perform more computations at switching nodes, which significantly improves the network's relaxation and its response to perturbations.

Current clinical practice lacks an accurate predictor of the femoral fracture risk in patients suffering metastatic bone disease, which results in large numbers of patients who are overand undertreated with complex surgery [Hipp, 1995; Van der Linden, 2003]. Previously, patient-specific finite element (FE) models have shown to be very promising in the prediction of femoral bone strength in vitro [Bessho, 2007; Keyak, 2005; Tanck, 2009]. The aim of the current in vivo study is to assess whether patient-specific FE models are able to discriminate low-risk patients with a pathological fracture from low-risk patients who did not fracture their femur.

A Purtscher-like retinopathy occurred in a 41-year-old woman who underwent the excision of a pterygium after a retrobulbar injection of 3 ml of lidocaine HCl. Visual acuity increased from 20/200 on the first postoperative day to 20/25, 12 weeks later. The exudates and the hemorrhages progressively disappeared. However, a relative, localized, paracentral scotoma and an afferent pupil defect still persist. The pathophysiology of this Purtscher-like retinopathy is discussed.

The aim of this paper is to show how evolutionary algorithms can be applied to protein folding prediction. We start reviewing previous similar approaches, that we criticize emphasizing the key issue of representation. A new evolutionary algorithm is described, based on the notion of distance matrix representation, together with a software package that implements it. Finally, experimental results are discussed.