Publications by authors named "Anna Bogdali"

17 Publications

  • Page 1 of 1

Status of CHEK2 and p53 in patients with early-onset and conventional gastric cancer.

Oncol Lett 2021 May 3;21(5):348. Epub 2021 Mar 3.

Department of Human Anatomy, Medical University of Lublin, 20-090 Lublin, Poland.

Gastric cancer (GC) is the fourth most common cause of cancer-associated death. Based on the age at diagnosis, GC is divided into early-onset GC (EOGC; ≤45 years) and conventional GC (CGC; >45 years). Mutations in the cell cycle checkpoint kinase 2 () and genes are associated with several types of cancer; however, their genetic defects in GC remain poorly understood. The aim of the present study was to determine the subcellular distribution of the CHEK2 protein and its redistribution following DNA damage, to improve the understanding of the DNA damage response. Genetic alterations and patterns of expression of CHEK2 and p53 proteins were investigated to identify potential biological markers and indicators of GC development. Additionally, the affected signaling pathways and their clinical importance in GC development and associated syndromes were investigated. A total of 196 GC samples (89 CGC and 107 EOGC samples) were used in the present study. DNA from 53 samples (18 CGC and 35 EOGC samples) was sequenced using targeted next-generation sequencing technology to identify and compare common and rare mutations associated with GC. Subsequently, the cytoplasmic and nuclear expression levels of CHEK2, phosphorylated (p)-CHEK2 at threonine 68 and p53 in GC tissues were determined via immunohistochemistry. Sequencing resulted in the identification of 63 single nucleotide polymorphisms (SNPs) in the gene amongst 5 different variants, and the intron variant c.319+379A>G was the most common SNP. In the gene, 57 different alterations were detected amongst 9 variant types, and the missense variant c.215C>G was the most common. Nuclear CHEK2 expression was high in both the EOGC and CGC subtypes. However, the prevalence of cytoplasmic CHEK2 expression (P<0.001) and nuclear p-CHEK2 expression (P=0.011) was significantly higher in CGC compared with in EOGC tissues. There was a statistically significant difference between high and low cytoplasmic CHEK2 expression in patients with p53-positive EOGC compared with in patients with p53-positive CGC (P=0.002). The present study was designed to determine the association between CHEK2 and p53 expression patterns in patients with EOGC and CGC, as well as genetic alterations in the and genes.
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http://dx.doi.org/10.3892/ol.2021.12609DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7967923PMC
May 2021

Genetic variants of gene in Polish patients with hereditary angioedema due to C1 inhibitor deficiency.

Cent Eur J Immunol 2020 1;45(3):301-309. Epub 2020 Nov 1.

Greater Poland Center of Pulmonology and Thoracic Surgery, Poznan, Poland.

Hereditary angioedema due to C1-inhibitor deficiency (C1-INH-HAE) type I and II is a rare and life-threatening disease caused by SERPING1 gene mutations. Previous genetic studies indicated a wide spectrum of disease-associated variants in the SERPING1 gene and often lack of correlation with patient's phenotypes. The aim of this study was to evaluate the presence, type, and localization of mutations in the SERPING1 gene in 41 Polish patients with C1-INH-HAE and their relation with case/family history, type of C1-INH-HAE, fC1-INH, age of onset, and disease severity. Sanger sequencing and MLPA method were used for detection of disease-associated variants. In 34 (82.9%) patients, mutations located in various regions of SERPING1 gene were revealed. The detected alterations in patients with C1-INH-HAE type I differed and were positioned in various exons/introns of the SERPING1 gene. The most frequent disease-associated variants appeared in exon 3 (especially in type I) and in exon 8 (type I and II). Out of 20 different disease-causing variants, 9 were not previously described. We did not find any relation between the type and location of the mutations and no type of features included in phenotype evaluation of the patients, such as case and family history, type of C1-INH-HAE, age of onset, biochemical parameters, or severity of disease.
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http://dx.doi.org/10.5114/ceji.2020.101252DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7790005PMC
November 2020

Analysis of local recurrence causes in uveal melanoma patients treated with I brachytherapy - a single institution study.

J Contemp Brachytherapy 2019 Dec 16;11(6):554-562. Epub 2019 Dec 16.

Department of Ophthalmology and Ocular Oncology of the Jagiellonian University, Medical College, Kraków, Poland.

Purpose: To perform a retrospective analysis of factors which might affect the occurrence of a relapse of uveal melanoma after I brachytherapy.

Material And Methods: The analysis concerned 343 patients treated in the years 2001-2012. The effect on local recurrence of such factors as patient's sex, age, tumour size, shape, pigmentation, location, presence of orange pigment or petechiae on tumour surface, retinal detachment, and blood or dispersed pigment in vitreous body were studied. Additional analysis concerned physical properties of brachytherapy (total dose, irradiation dose applied to tumour apex and base and irradiation time). Two groups of patients were distinguished: with and without a relapse. The diagnostic criterion for the relapse was growth of the tumour base or height by 0.5 mm.

Results: Local recurrence of the uveal melanoma was observed in 29 patients (8.5%). Recurrences occurred with significantly higher frequency ( < 0.001), when the anterior tumour edge involved the ciliary body. Patients' survival in relation to the moment the occurrence of the relapse was statistically significant for application time ( = 0.004) and tumour pigmentation ( = 0.010). The deaths of patients with a local relapse were most rare when brachytherapy lasted from 72 to 95.9 hours and most frequent in cases of brownish tumour pigmentation. Patient sex, tumour shape and size, presence of orange pigment, retinal detachment, petechiae and bleeding to vitreous body as well as the dose of irradiation to tumour top and base did not have any significant effect on relapse occurrence.

Conclusions: Treatment of uveal melanomas with I applicators allows for a high rate of positive local results. Nonetheless, the recurrence probability always exists. The involvement of the ciliary body could influence this. The survival depending on the time of relapse could be statistically significant for application time and dark-brown tumour pigmentation.
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http://dx.doi.org/10.5114/jcb.2019.90985DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6964341PMC
December 2019

Bradykinin and oxidative stress in patients with hereditary angioedema due to C1 inhibitor deficiency.

Pol Arch Intern Med 2020 02 14;130(2):79-88. Epub 2020 Jan 14.

Department of Clinical and Environmental Allergology, Jagiellonian University Medical College, Kraków, Poland

Introduction: Hereditary angioedema (HAE) is a rare autosomal dominant disease caused by genetic dysfunction of C1 inhibitor (C1-INH) due to mutations in the SERPING1 gene. The disorder is mediated mainly by bradykinin. The clinical course of the disease is varied and not related to genetic changes.

Objectives: We aimed to evaluate redox homeostasis of peripheral blood mononuclear cells (PBMCs) in patients with HAE due to C1-INH deficiency (C1 INH HAE) by measuring the levels of reactive oxygen species (ROS) of PBMCs as well as plasma advanced glycation end products (AGEs) and advanced oxidation protein products (AOPPs). We also aimed to assess the effect of bradykinin on ROS levels.

Patients And Methods: We enrolled 30 adults with C1-INH-HAE and 15 healthy individuals. The levels of ROS were measured by flow cytometry, while the plasma levels of AGEs and AOPPs were determined spectrophotometrically by enzyme‑ linked immunosorbent assays.

Results: Basal and hydrogen peroxide (H2O2)-induced ROS levels were higher in patients with HAE when compared with controls (P = 0.002 and P = 0.001, respectively), indicating abnormalities in redox homeostasis. Plasma AOPP and AGE levels were similar in both groups. Bradykinin reduced basal and H2O2-induced ROS generation in PBMCs only in patients with HAE (P = 0.03).

Conclusions: The higher basal and H2O2-induced ROS levels in patients with C1 INH HAE indicate redox imbalance. However, by reducing basal and H2O2-induced ROS levels, bradykinin shows antioxidant action in this disorder.
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http://dx.doi.org/10.20452/pamw.15138DOI Listing
February 2020

Outcomes of I-125 brachytherapy for uveal melanomas depending on irradiation dose applied to the tumor apex - a single institution study.

J Contemp Brachytherapy 2018 Dec 28;10(6):532-541. Epub 2018 Dec 28.

Department of Ophthalmology and Ocular Oncology of University Hospital, Cracow.

Purpose: The aim of the study was an evaluation of I-125 brachytherapy patients with uveal melanoma with special consideration for the relationship of the treatment results and the irradiation dose applied to the tumor apex.

Material And Methods: Medical records of 344 adults with uveal melanoma treated with I-125 brachytherapy in the Department of Ophthalmology and Ocular Oncology of the Jagiellonian University, Medical College in Cracow, Poland were retrospectively analyzed. The study was conducted between 2003 and 2012, and the study group was divided into two subgroups depending on the irradiation dose applied to the top of the tumor: 80 Gy to 100 Gy ( = 177) and 100 Gy to 120 Gy ( = 167).

Results: It was found that the height of the tumor and the largest diameter of the tumor base decreased with every consecutive follow-up measurement and differed significantly in all comparisons ( < 0.0001). No significant correlation between frequency of complications was found between both study groups (χ = 0.27; = 0.6067). The correlation between survival and the irradiation dose as applied to the tumor top was statistically irrelevant (χ = 0.44; = 0.5084). A logistic regression model showed that patient survival depended on the largest diameter of the base and the height of tumor ( = 0.0216), and the risk of death was larger as these dimensions increased (IR, 1.17). An increase of the largest diameter of the base by 1 mm meant a 17% increase in chances of death. In 13.4% of cases, an enucleation was necessary.

Conclusions: The treatment of choroidal melanomas with I-125 iodine isotope brachytherapy is an efficient and recommended method of treatment and in many cases, an alternative to the enucleation of an eyeball.
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http://dx.doi.org/10.5114/jcb.2018.79886DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6335559PMC
December 2018

Analysis of gene expression to predict dynamics of future hypertension incidence in type 2 diabetic patients.

BMC Proc 2016 18;10(Suppl 7):113-117. Epub 2016 Oct 18.

Center for Medical Genomics-OMICRON, Jagiellonian University Medical College, Kraków, Poland.

Background: The main focus of the Genetic Analysis Workshop 19 (GAW19) is identification of genes related to the occurrence of hypertension in the cohort of patients with type 2 diabetes mellitus (T2DM). The aim of our study was to predict dynamics of the future hypertension incidence, based on gene expression profiles, systolic and diastolic blood pressure changes in time, sex, baseline age, and cigarette smoking status. We analyzed data made available to GAW19 participants, which included gene expression profiles of peripheral blood mononuclear cells (PBMCs) from the diabetic members of 20 Mexican American families.

Methods: On the basis of mid blood pressure measurements at several time points, the coefficient of regression (slope) was calculated for each individual. We corrected the slope value in patients treated with antihypertensive medications. Feature preprocessing methods were used to remove highly correlated probes and linear dependencies between them. Subsequently, multiple linear regression model was used to associate gene expression with the regression coefficient calculated for each T2DM patient. Tenfold cross-validation was used to validate the model. We used linear mixed effects model and kinship coefficients to account for the family structure. All calculations were performed in R.

Results: This analysis allowed us to identify 6 well-annotated genes: and associated with dynamics of future hypertension incidence. Two of them, and were previously implicated in pathogenesis of hypertension.

Conclusions: There is no obvious mechanism that links all detected genes with dynamics of hypertension incidence. Identification of possible connection with hypertension needs further investigation.
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http://dx.doi.org/10.1186/s12919-016-0015-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5133526PMC
October 2016

Recurrence of choroidal melanoma after Ru- 106 brachytherapy.

Klin Oczna 2016 Sep;117(4):249-252

Aim: The aim of the study was to analyse the recurrence rates of choroidal melanoma treated with Ru-106 brachytherapy with or without adjunctive transpupillary thermotherapy.

Material And Methods: We analysed medical records of 97 patients treated with Ru-106 brachytherapy with or without adjunctive transpupillary thermotherapy who subsequently presented with recurrence. All patients were treated at the Department of Ophthalmology and Ocular Oncology in Krak6w between 1995 and 2006.

Results: The mean time to recurrence was 29.15 months and tended to be shorter in larger melanomas. The 5-year recurrence rate determined using Kaplan-Meier estimator was 28.69%. Marginal recurrence was the most common type of recurrence, especially in tumors adjacent to the optic disc. The recurrence rates were the highest for all types of recurrence after the use of COB plaque with or without adjunctive transpupillary thermotherapy.

Conclusion: The highest incidence of recurrence was shown in the second year following the Ru-106 brachytherapy and the time to recurrence tended to be shorter in larger melanomas. Marginal recurrence was the most common type of recurrence, especially in tumors adjacent to the optic disc.
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September 2016

Corrigendum to "Nickel allergy and relationship with Staphylococcus aureus in atopic dermatitis" [J. Trace Elem. Med. Biol. 33 (2016) 1-7].

J Trace Elem Med Biol 2016 May 7;35:126. Epub 2016 Mar 7.

Department of Clinical and Environmental Allergology, Jagiellonian University Medical College, 31-531 Krakow, Poland. Electronic address:

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http://dx.doi.org/10.1016/j.jtemb.2016.02.004DOI Listing
May 2016

The Pediatric Choroidal and Ciliary Body Melanoma Study: A Survey by the European Ophthalmic Oncology Group.

Ophthalmology 2016 Apr 4;123(4):898-907. Epub 2016 Feb 4.

Department of Ophthalmology, Poznán University of Medical Sciences, Poznán, Poland.

Purpose: To collect comprehensive data on choroidal and ciliary body melanoma (CCBM) in children and to validate hypotheses regarding pediatric CCBM: children younger than 18 years, males, and those without ciliary body involvement (CBI) have more favorable survival prognosis than young adults 18 to 24 years of age, females, and those with CBI.

Design: Retrospective, multicenter observational study.

Participants: Two hundred ninety-nine patients from 24 ocular oncology centers, of whom 114 were children (median age, 15.1 years; range, 2.7-17.9 years) and 185 were young adults.

Methods: Data were entered through a secure website and were reviewed centrally. Survival was analyzed using Kaplan-Meier analysis and Cox proportional hazards regression.

Main Outcome Measures: Proportion of females, tumor-node-metastasis (TNM) stage, cell type, and melanoma-related mortality.

Results: Cumulative frequency of having CCBM diagnosed increased steadily by 0.8% per year of age between 5 and 10 years of age and, after a 6-year transition period, by 8.8% per year from age 17 years onward. Of children and young adults, 57% and 63% were female, respectively, which exceeded the expected 51% among young adults. Cell type, known for 35% of tumors, and TNM stage (I in 22% and 21%, II in 49% and 52%, III in 30% and 28%, respectively) were comparable for children and young adults. Melanoma-related survival was 97% and 90% at 5 years and 92% and 80% at 10 years for children compared with young adults, respectively (P = 0.013). Males tended to have a more favorable survival than females among children (100% vs. 85% at 10 years; P = 0.058). Increasing TNM stage was associated with poorer survival (stages I, II, and III: 100% vs. 86% vs. 76%, respectively; P = 0.0011). By multivariate analysis, being a young adult (adjusted hazard rate [HR], 2.57), a higher TNM stage (HR, 2.88 and 8.38 for stages II and III, respectively), and female gender (HR, 2.38) independently predicted less favorable survival. Ciliary body involvement and cell type were not associated with survival.

Conclusions: This study confirms that children with CCBM have a more favorable survival than young adults 18 to 25 years of age, adjusting for TNM stage and gender. The association between gender and survival varies between age groups.
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http://dx.doi.org/10.1016/j.ophtha.2015.12.024DOI Listing
April 2016

Uveal melanoma – is a biopsy safe and justified?

Klin Oczna 2016;118(2):151-4

Uveal melanoma can be typically diagnosed based on clinical presentation and the A and B mode ultrasound. In some atypical intraocular tumours or for prognostic purposes intraoperative biopsy may be performed. Uveal melanoma biopsy is not safe in 100% and can cause complications (vitreous hemorrhage, retinal detachment and endophthalmitis). Like all biopsies, a biopsy in uveal melanoma biopsy may show limited cellularity and can yield insufficient tissue specimen for histology, cytology and genetic testing. This is most likely in small tumours, below 3 mm in thickness. Another limitation of biopsy-based prognosis is the issue of intratumoural heterogeneity. As a biopsy allows for only a small sample to be removed from the tumour, it is possible to receive false negative results. The most devastating complication of uveal melanoma biopsy is the extraocular spread of the tumour. The study is a review of the current opinions and findings on the role of biopsy in uveal melanoma.
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July 2018

Imaging choroidal osteoma with the Deep Range Imaging Optical Coherence Tomography – a case report.

Klin Oczna 2016;118(2):133-5

Choroidal osteoma is a rare, benign tumor which primarily affects young females, occurring at the posterior pole of the eye. Differential diagnosis, based on ophthalmoscopy, ocular ultrasound and modern techniques such as Deep Range Imaging Optical Coherence Tomography, should include amelanotic choroidal melanoma or metastatic tumors. This case report outlines the features of choroidal osteoma imaged using the Deep Range Imaging Optical Coherence Tomography, namely its lamellar and spongy bone structure, sclero-choroidal junction, tumour transparency, parallel horizontal and vertical canals communicating the lesions, as well as the presence of calcified and decalcified regions.
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July 2018

Molecular methods of diagnosing allergic sensitization in patients with atopic dermatitis and infected by with Staphylococcus aureus.

Przegl Lek 2016;73(12):818-22

The severity of allergic symptoms in patients with atopic dermatitis (AD) intensifies when the number of colonies patient’s of Staphylococcus aureus on patents’ skin increases. The basic feature determining the quality of any diagnostic test for S. aureus is its credibility. Performing a test always carries the risk of obtaining false positive and/or false negative results. Furthermore, producing material for microbiological analysis of internal body cavities is sometimes difficult. Therefore, in our study, we compared the results of three tests to determine if their results were mutually compatible and if they confirmed whether S. aureus was present in patients with AD and what was its role in the development of the disease in those patients. Infection with S. aureus was tested in patients with AD and healthy volunteers using the API Staph system. The specific IgE antibodies for staphylococcal enterotoxin A (SEA) and B (SEB) were measured using the UniCAP system. The secretion of IFN-γ, IL-2, IL-13 by peripheral blood mononuclear cells (PBMCs) after stimulation with SEA and SEB were studied with Elispot assay. We found that only certain patients with AD and S. aureus produced antibodies against SEA and SEB in the acute phase of AD. The secretion of IFN-γ was low in patients with exacerbated AD and S. aureus. Testing for the presence of S. aureus in the mucous membrane of the nasal vestibule and skin lesions is not sufficient for complex diagnosis of the role of S. aureus in the pathomechanism of AD. Measuring the presence of antibodies against bacterial components in patients’ serum and the reactivity of patients’ immune cells against these bacterial components is required in order to accurately diagnose this role of S. aureus in a patient.
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June 2018

Nickel allergy and relationship with Staphylococcus aureus in atopic dermatitis.

J Trace Elem Med Biol 2016 Jan 20;33:1-7. Epub 2015 Jul 20.

Department of Clinical and Environmental Allergology, JagiellonianUniversity Medical College, 31-531 Krakow, Poland.

Background: The increase of nickel air pollution is supposed to frequent side effects of nickel action related to virulence potential of Staphylococcus aureus in patients with nickel allergy in atopic dermatitis. The goal was to investigate the relationship between nickel allergy and infection by S. aureus in atopic dermatitis.

Methods: Nickel allergy was confirmed in atopic patients and excluded in healthy volunteers using patch testing. Infection by S. aureus was tested in atopic patients and healthy volunteers by use of API Staph system. The specific IgE for staphylococcal enterotoxin A and B were measured. Secretion of IFN-g, IL-2, IL-13 by PBMC under nickel sulfate and the enterotoxins A and B stimulations were studied with ELISpot.

Results: We found the increased number of infections by S. aureus in atopic patients with nickel allergy in comparison to atopic patients and healthy volunteers without nickel allergy. The elevated secretion of IL-2 under nickel sulfate stimulation in vitro was exclusively found in atopic patients with nickel allergy infected by S. aureus.

Conclusions: Our data suggest that nickel allergy and infection by S. aureus are linked in atopic dermatitis.
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http://dx.doi.org/10.1016/j.jtemb.2015.06.009DOI Listing
January 2016

Bilateral choroidal melanoma--case analysis and literature review.

Klin Oczna 2015 ;117(2):92-5

Uveal melanoma is the most common primary intraocular neoplasm in adults. Its bilateral localization is extremely rare. The aim of the paper is analysis of the cases of bilateral uveal melanoma. Five bilateral uveal melanoma patients were diagnosed in the Department of Ophtalmology and Ocular Oncology beetwen 1980 and 2014. Both eyes of four patients were threated with brachytherapy. Final enulcleation of the one eye was performed in three patients. It was the primary treatment in one patient. The presence of uveal melanoma was confirmed by pathological examination in all cases after surgical removal of eyeball and in one after local resection of iris tumor. Metastatic lesions were diagnosed in lungs and liver in two patients. Three patients are still followed-up at our institution. The possibility of bilateral uveal melanoma should considered although it is extremely rare. bilateral uveal melanoma, brachytherapy, enucleation.
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January 2016

[Risk factors for the recurrence of choroidal melanoma after the Ru-106 brachytherapy].

Klin Oczna 2015 ;117(3):169-72

Purpose: The aim of the study was to determine factors, which are likely to affect local recurrence of choroidal melanoma after ruthenium-106 brachytherapy with or without adjunctive transpupillary thermotherapy.

Material And Methods: We analysed 355 cases of patients with choroidal melanoma treated ruthenium-106 brachytherapy with or without adjunctive transpupillary thermotherapy. These were divided into two groups of patients with confirmed recurrence of choroidal melanoma (97 subjects) and patients without recurrence (control group, 258 subjects).

Results: We found a significant relationship between tumour recurrence and the presence of retinal detachment at the time of diagnosis, tumor shape, its large size and location with the marginal adjacency to the optic disc and with the anterior margin located 1-2 optic disc diameters from the macula. Among other risk factors, the use of COB plaque with supplementary transpupillary thermotherapy, dose to the tumor base, visibility of tumor base shade during transillumination, and uncertainty regarding precise plaque placement showed a significant correlation with tumour recurrence, just as the presence of metastases did.

Conclusion: It seems that large tumour size and its location at the proximity of the optic disc are the key factors to affect the failure of brachytherapy and recurrence in patients with choroidal melanoma.
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May 2016

[The familial occurrence of choroidal melanoma].

Klin Oczna 2014 ;116(2):123-6

In 2010 we treated one case of familial choroidal melanoma which was detected in a mother and a daughter at the Department of Ophthalmology and Ocular Oncology University Hospital in Krakow. The enucleation was performed in a daughter, while the mother refused to give an informed consent to the procedure despite the diagnosis of ring melanoma, and was eventually subjected to brachytherapy. In both cases histopathological examination confirmed melanoma. Both patients and their relatives have remained in a follow-up until now. Results: Inheritance may play a role in the etiology of melanoma. Therefore, each time melanoma is diagnosed, the close relatives of the patients should undergo regular eye tests.
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November 2014

[Proton beam radiotherapy of uveal melanoma--preliminary results].

Klin Oczna 2012 ;114(3):173-9

Klinika Okulistyki i Onkologii Okulistycznej Katedry Okulistyki, Uniwersytetu Jagiellońskiego Collegium Medicum w Krakowie.

Purpose: Presentation of the proton beam radiotherapy (PBR) as a method of treatment of the uveal melanoma patients in the Department of Ophthalmology and Ocular Oncology and Nuclear Physics Institute in Cracow, Poland and their preliminary results.

Material And Methods: Nine patients with only choroidal melanoma were treated using PBR between January and April 2011. There were 4 women (44%) and 5 men (56%), a mean age 56 years (38-72). The mean tumor thickness using ultrasounds was 4.14 mm (1.4-9.6 mm).

Results: The mean follow-up was 6 months (5-7). The mean tumor thickness after PBR was 2.47 mm (0-9.3 mm). In 2 patients endoresection of irradiated tumor mass was performed with final flat scar. After exclusion of these patients from analysis, the mean thickness was 3.17 mm (1.5-9.3 mm). In 6 patients the visual function was stable.

Conclusions: The preliminary results show that PBR is highly precise method of uveal melanoma treatment achieving high rates of local control. This method necessitates a close co-operation between ophthalmologist, oncologist, radiotherapists, and medical physicist as well as an elaboration of own procedures of planning and treatment. uveal melanoma, radiotherapy, proton-beam radiotherapy.
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March 2013