Prognostic value of apoptosis inducing factor in uveal melanoma.

In malignant tumors including uveal melanoma there is a continuous effort in search for additional and relevant factors with predictive value and possible therapeutic indications. In the present work we evaluated the 5-year mortality in a group of patients with surgically treated uveal melanoma and its relation to selected demographic, clinical and histopathological parameters, including the expression of apoptosis inducing factor (AIF) in the neoplastic tissue.We analyzed retrospectively the clinical data of patients with uveal melanoma treated surgically (enucleation, endoresection, exenteration) in the period from 2001 to 2007 (n=54). Immunohistochemical detection of AIF expression in formalin fixed and in paraffin embedded tissue samples was evaluated semiquantitatively, intensity and percentage multiplicative Quick Score (QS) was calculated and compared between patients with over 5 year (n=32) and less than 5 year (n=22) survival. In the analyzed group of 54 patients the 5 year mortality was 41 %. We confirmed the negative prognostic significance of some of the known prognostic factors as the tumor size and volume, T3 and T4 stage in the TNM classification and the mixed histological type of the tumor. Immunohistochemistry performed on 49 melanoma specimens showed AIF cytoplasmic positivity, no nuclear translocation was detected. The cut-off value of AIF expression QS ≥ 4 (18) in tumor cells separated the 5 year survival of patients (P = 0.018), odds ratio 5.2 (1.24 - 21.73). Moderate and strong expression of AIF in tumor cells also correlated with less favorable prognosis. Confocal microscopy proved colocalization of AIF with mitochondrial marker in neoplastic cells.The prognosis of patients with uveal melanoma can be more accurate with inclusion of immunohistochemical detection of AIF expression. Increased expression of the AIF protein appears as a new negative prognostic factor predicting the 5 year survival.

Therapy of melanocytic conjunctival tumors.

BACKGROUND: Clinical experience of our single center in dealing with pigmented epibulbar lesions - melanocytic conjunctival tumors is presented. Since 2008 we use the topical treatment with mitomycin C (MMC) as an alternative or adjunctive method for excision in the treatment of melanocytic neoplasia of the conjunctiva. METHODS: The retrospective case series of 85 patients with pigmented lesions of the conjunctiva - melanocytic conjunctival tumors, histopathologically examined in the period 2001-2010 is presented. Since 2008 we started to apply MMC in the treatment of primary acquired melanosis (PAM) and dysplastic nevi. We apply MMC topically directly after an excision as 2-times five minutes application. RESULTS: In 85 patients with pigmented lesions of the conjunctiva histopathological findings after excision of the lesion showed in 68 (80 %) cases melanocytic nevocelullar nevus, out of which 55 cases were combined and 13 cases were junctional nevi. In 60 (80 %) cases of melanocytic nevi atypia was found in 25 patients (42 %), nevus without atypia was present in 35 cases (58 %). PAM with atypia was found in 16 patients (classified since 2000). During the period of application of MMC we diagnosed only one patient with primary conjunctival melanoma. There was no presence of relapse of the pigmented lesion either after primary excision or after excision with MMC. CONCLUSION: Resection of more than one quadrant of bulbar conjunctiva in patients with pigmented lesions of the conjunctiva in cases of conjunctival nevus with atypia and PAM with atypia combined with topical MMC chemotherapy is an alternative therapy for residual pigmented lesions. There was no presence of relapse of pigmentation in area of excision with or without using MMC during the surgery in patients with PAM. The number of our patients is not sufficient yet to draw a conclusion (Fig. 6, Ref. 21).

[Late metastasis development in two cases of small choroidal melanoma]. / Neskorý rozvoj metastáz u pacientov s malým melanómom choroidey - 2 kazuistiky.

PURPOSE: To present data pointing out that small tumour size might not be a sufficient predictor of good prognosis of choroidal melanoma and present a new promising therapy of hepatic metastasis. METHODS: Retrospective, noncomparative case report of two patients with small choroidal melanoma. RESULTS: Two cases of small choroidal melanoma which developed metastases are described. Both patients underwent radiotherapy of the primary tumour. Metastases were treated by combined therapy in patient 1 while in patient 2 a new therapeutic modality of stereotactic radiotherapy, Cyberknife, was applied. Patient 1 died from metastatic spread 7,6 years after primary therapy despite a very good local tumour control. Patient 2 died 11,3 years after primary therapy due to intercurrent disease with a very good local eye findings and hepatic metastasis in regression. CONCLUSION: Choroidal melanoma of a small size can develop into metastatic disease even long time after satisfactory primary treatment. Further studies are required to assess the risk factors of metastatic spread in small uveal melanomas. Cyberknife stereotactic radiotherapy seems to be a promising therapeutic method of a solitary hepatic metastasis. Key words: choroidal melanoma, metastasis, prognostic factors, stereotactic radiotherapy.

[Extrascleral overgrowth of malignant choroidal melanoma after endoresection]. / Extrasklerálne prerastanie malígneho melanómu choroidey po endoresekcii.

OBJECTIVE: Course of progression of the malignant choroidal melanoma diagnosed in T2 stage up to stage T4 with infiltration of the orbit. Case report 41 year old patient identified with intraocular malignant melanoma in the year 2005, documentation of disease progression and disease. Access to treatment of intraocular malignant melanoma in stage T1 - T2 in the last decade has changed from a radical approach (enucleation) towards conservative treatment (brachytherapy, radiosurgical methods) or combined procedures (pars plana vitrectomy and endoresection followed by irradiation or addition of laser treatment). Currently, more than 60% of uveal melanoma is treated by brachytherapy or radiosurgical techniques and combined procedures. CASE REPORT: A 41 years old female patient with malignant melanoma in the choroid stage T2 since 2005. The volume of the tumor was 0.9 cm³, maximal elevation was over 12 mm. The patient refused a radical treatment (primary enucleation). Due to the stage of the melanoma she was recommended to stereotactic radiosurgery and combined therapy. She underwent stereotactic radiosurgery (TDmax - total dose of 35.0 Gy) in 2005. In 2006 pars plana vitrectomy with incomplete endoresection of the tumor and silicon oil instillation was done. In 2006-2007 appeared bleeding into the anterior chamber and she underwent three times an anterior chamber lavage in another department with subsequent development of secondary glaucoma. In January 2010 patient came to our department with the local finding of malignant melanoma in stage T4 with epibulbar growth process and the infiltration of the orbit. In the period have been found two solid liver metastases. Indicated exenteration of the orbit, histopathologically confirmed mixed cell type malignant melanoma. CONCLUSION: Progression of malignant melanoma after incomplete endoresection despite previous radiosurgical treatment can be very rapid in the course of the disease documented by ultrasound, computed tomography and magnetic resonance. The patient subsequently passed to another workplace and underwent repeated lavage of the vitreous cavity. During endoresection is opened the package fibrous mesh gateway for the infiltration process in the cavity of the orbit and epibulbar space. In the case of residual melanoma after endoresection even though the tumor was irradiated before the procedure the melanoma might progress very fast into the surrounding tissues.

[Selected prognostic factors of malignant uveal melanoma]. / Vybrané prognostické faktory malígneho melanómu uvey.

Malignant uveal melanoma is the most common intraocular tumor in adults. Despite very good local treatment results, patients' survival has not improved in the last decades. The main cause of death is metastatic spread, which occurs with a variable time delay after tumor discovery in 50% of patients. After metastasis development the mean survival rate decreases to less than 6 months. Progression to metastatic disease is associated with different prognostic factors. The spectrum of conventional clinical and histopathologic prognostic factors like age, tumor size, location, extrascleral growth, histopathologic cell type, vascularisation, invasion of sclera, etc., has been enlarged by using new immunological, molecular, immunohistochemical and cytogenetical methods. Current research also focuses on development of an adjuvant systemic therapy which could delay or prevent metastasis development in high-risk patients. It is necessary to determine reliable prognostic factors in order to select potential candidates for such a systemic treatment. In this article we present a short overview of known prognostic factors of uveal melanoma.

[The current state of the evidence of malignant tumors of the eye and its adnexa (dg. C69) in the Slovak Republic and in the Czech Republic]. / Súcasný stav evidencie zhubných nádorov oka a ocných adnexov (dg. C69) v SR a CR.

The area of ophthalmooncology includes not only intraocular tumors but also adnexal and extraocular tumors, relatively rare malignancies. To get valid data and to study the incidence, diagnosis and treatment is extremely difficult. The most frequently occurring intraocular tumor in adults is malignant melanoma, in children it is retinoblastoma. We present the results of the nationwide group of patients based on the diagnosis report C69 - Tumors of the eye and adnexa according to data of the National Cancer Registry in Slovak Republic. We monitor the incidence, distribution by age group, survival and staging. In the second part of the thesis analyzed data are compared with the data from Cancer Registry in the Czech Republic. After analyzing the data, we found that the incidence of intraocular tumors have been reported to be comparable with neighbouring countries. The classification of the disease in different stages due to TNM classifying in the report is below 50 % in Slovakia. The incidence observed in each year ranges from 0.6 to 1.0 per 100 000 inhabitants. Survival of patients with dg. C69 is comparable with other countries. The proportion of clinically defined stages of the disease is in the database of Slovakia lower than in the Czech Republic. The delay of inserting data of patients in the National Cancer Registry in Slovakia and the availability of data for analysis is currently unsatisfactory. In Slovakia are available data only up to year 2003, in Czech Republic up to year 2009.

Malignant hemophtalmus as a first sign of orbital rhabdomyosarcoma in adult.

We report on a rare case of an adult patient with rhabdomyosarcoma treated at the Dpt Ophthalmology, Comenius University, Medical School in Bratislava as a single case since 1968 (Fig. 2, Ref. 5). Full Text in free PDF www.bmj.sk.

[Basalioma of the eyelid: rate and factors of recurrence after surgical therapy]. / Výskyt recidív po chirurgickej liecbe bazaliómu koze mihalníc.

UNLABELLED: The aim of our study was to evaluate a recurrence rate of basalioma of the eyelid after surgical therapy. In our cohort of patients we also assessed a relation between the recurrence and chosen clinical parameters (localisation and size of tumour, TNM classification, histopathological grade of differentiation, margins of excision). MATERIAL AND METHODS: Retrospective analysis of data from patients with basalioma of the eyelid treated surgically at the Department of Ophthalmology, Faculty of Medicine Comenius University in Bratislava during the years 2005-2007. The excision exceeded the macroscopically visible margins of tumor with a safety margin of 2-3 mm into the healthy tissue. RESULTS: In our cohort we studied 67 histologically proven tumors in 65 patients. During a mean follow-up time of 24.6 +/- 13.6 months we found a recurrence in 4 tumors (6,0%), one of them subsequently recidivated for a second time. There was no statistically significant relation between the studied parameters and a tumor recurrence. CONCLUSION: Our recurrence rate of 6.0% is comparable with the published results from other centers.

[The embedded mobile orbital implant from methylmethacrylate "Hydron"--clinical and histopathological findings 25 years after implantation]. / Zanorený pohyblivý orbitálny implantát z methylmetakrylátu "hydron"--klinický a histopatologický obraz 25 rokov po implantácii.

The embedded mobile hydrogel methylmethacrylate ("HYDRON" Spofa) orbital implants introduced in the beginning of 70th years of 20th century was a new method to get good cosmetic effects after enucleation. At the Dept. of Ophthalmology of the Comenius University, Bratislava, the rejection rate of this type of orbital implants in the first years after enucleation (1971-1974) was only 16.8%. This technique was applied in patients after enucleation due to traumatic phtisis of the eye globe. Authors submit a case report of a female patient from the group of implanted mobile orbital implant HYDRON implanted in 1984. They analyze clinical features and histopathological findings after surgical removement 25 years after implantation.