Uveal melanoma dissemination within the scleral tract in fine needle aspiration biopsy

Introduction. Fine needle aspiration biopsy (FNAB) of uveal melanoma (UM) is an invasive procedure. Many authors consider UM FNAB to be safe procedure, however extraocular extension of the tumor through the scleral tracts may occur. Current studies of scleral tracts after FNAB do not compare different biopsy techniques (cannula-assisted and without cannula) in terms of UM cells.Purpose. To assess morphology of scleral tracts for the presence of malignant cells when different biopsy techniques are approached.Material and methods. Forty-four scleral samples were analyzed after transvitreal FNAB performed in 22 enucleated eyes with UM. Cannula-assisted FNAB was performed in 22 cases. In the same eyes FNAB (n=22) was performed without cannula.Results. FNAB material was adequate for cytological examination in all cases. UM was confirmed in 22 eyes pathologically. UM cell implantation was detected in 5 scleral samples after FNAB without cannula. No signs of cell implantation were seen after cannula-assisted FNAB. The risk of scleral tract UM cell implantation was statistically lower in cannula-assisted FNAB technique (p=0.018, Pearson Chi-square test).Conclusions. UM FNAB performed directly through the sclera without cannula is associated with tumor cells implantation in scleral tract. Cannula-assisted FNAB significantly reduces the incidence of UM implantation in scleral tract

The Hitting Times with Taboo for a Random Walk on an Integer Lattice

For a symmetric, homogeneous and irreducible random walk on d-dimensional integer lattice Z^d, having zero mean and a finite variance of jumps, we study the passage times (with possible infinite values) determined by the starting point x, the hitting state y and the taboo state z. We find the probability that these passages times are finite and analyze the tails of their cumulative distribution functions. In particular, it turns out that for the random walk on Z^d, except for a simple (nearest neighbor) random walk on Z, the order of the tail decrease is specified by dimension d only. In contrast, for a simple random walk on Z, the asymptotic properties of hitting times with taboo essentially depend on the mutual location of the points x, y and z. These problems originated in our recent study of branching random walk on Z^d with a single source of branching

Gamma Knife stereotactic radiosurgery for intraocular retinoblastoma: a 5-year experience

External beam radiotherapy (EBR) remained for a long time the only method of treatment in children with recurrent and resistant retinoblastoma (RB). This method often leads to serious complications, including the occurrence of secondary malignant tumors. Currently, EBR is used as second-line (salvage) therapy. There is no data in the literature of using Gamma Knife stereotactic radiosurgery (GKRS) in RB treatment.Purpose. To present 5-year experience of using GKRS in patients with RB.Material and methods. 16 children (17 eyes) were treated using GKRS in the period from 2015 to 2019. Mean patient age was 34.7 months (range, 12–114 months). The eyes were classified as group B (n=4), C (n=1), D (n=12). 3 children had the last eye. All patients received systemic and local chemotherapy, all types of local treatment modalities before using GKRS. Recurrent and resistant RB was the indication for GKRS. Marginal 50% mean dose was 22 Gу (range, 20–24 Gу), depending on tumour type and location. Radiation doses were evaluated accounting critical eye structures and the orbit bones.Results. Complete regression was achieved in 11 patients, partial in 2. Four patients underwent enucleation after GKRS. Indications for enucleation were retinoblastoma recurrence (n=2) and vitreous hemorrhage with total retinal detachment (n=2). 13 eyes were salvaged with no signs of keratopathy, uveitis or damage of orbital and surrounding tissues during mean follow-up 30.6 months (range, 7–60 months). Сomplications of different severity occurred in 13 patients, including vitreous hemorrhage in 6 patients, which was successfully treated both conservative (n=3) and using pars plana vitrectomy with simultaneous melphalan irrigation (n=3).Conclusion. The first experience of GKRS as an alternative to enucleation in patients with RB was proved to be reasonable and successful

Single-stage combined urethroplasty for extended strictures of the anterior urethra of tuberculous origin

Background. Urethral strictures are currently one of the most complex pathologies in reconstructive urology. The most promising direction in this area is the development of single-stage surgical interventions that meets modern requirements for the quality of life of patients.The aim of the study. To evaluate the possibility and the effectiveness of surgical treatment of extended recurrent tuberculous urethral strictures in men using a combination of a skin flap and a buccal graft. In the literature, there is no description of the use of this technique in patients with urethral tuberculosis.Materials and methods. We observed 44 patients with urethral tuberculosis. Three men from this group of patients were diagnosed with tuberculous (post-tuberculous) extended recurrent stricture of the anterior urethra and they underwent combined single-stage urethroplasty with a ventral fasciocutaneous flap and a buccal graft using the inlay method in the penile region and with a buccal graft using the ventral onlay method in the bulbous urethra. Ultrasound of the urethra served as a method that determines the possibility of performing this surgery in case of maintaining a sufficient width of the urethral plate with a moderate degree of spongiofibrosis.Results. Patients were under observation for 34, 50 and 54 months and have good long-term functional results – all patients have unassisted urination and no residual urine. Post-micturition dribbling persists in 1 patient. The overall effectiveness of the treatment of these strictures, taking into account the treatment of repeated cases of the disease recurrence, is high.Conclusion. This technique demonstrates the possibility of performing a single-stage reconstruction of the anterior urethra in patients with extended recurrent tuberculous (post-tuberculous) urethral strictures and is also applicable for the surgical treatment of urethral strictures of other origins

Survival prognosis in individuals with a high spatial QRS-T angle

Aim. To evaluate medium-term survival without irreversible and fatal cardiovascular events in individuals with a high spatial QRS-T angle (sQRS-Ta) from a regional Russian sample.Material and methods. We analyzed 1394 electrocardiographic records from a random regional sample of men (30%) and women aged 25-64, which were included in the ESSE-RF1 study. Women were on average 5 years older than men, but there was no difference in mean age in the 45-64 groups. The follow-up period lasted 7 year; 26 irreversible events (cardiovascular death, non-fatal myocardial infarction or stroke) and 63 composite endpoints (CEs) (irreversible event or heart failure progression or revascularization) were identified. Irreversible events and composite endpoint in men were noted more often than in women as follows: 3,7% vs 1,1% (p=0,003) and 6,9% vs 3,6% (p=0,01), respectively. sQRS-Ta was estimated as the angle between the integral QRS and T vectors in the orthogonal leads. Survival was assessed by Kaplan-Meier curves using a log-rank test. Differences were considered significant at p≤0,05. Results. Sex groups did not differ in mean sQRS-Ta. sQRS-Ta ≥90o was considered to be increased. The divergence of survival curves by the end of follow-up period in men with increased sQRS-Ta relative to men with sQRS-Ta <900 was greater than in women as follows: 0,88 vs 0,96 for CE (p=0,0026) and 0,93 vs 0,96 for irreversible events (p=0,009); in women — 0,94 vs 0,98 for CE only (p=0,0016). Initial event and CE in men with increased sQRS-Ta occurred earlier than those with normal sQRS-Ta and then in women with increased sQRS-Ta. There were no differences in the frequency of sQRS-Ta increase among 45-64-year-old men and women, but irreversible events in men with increased sQRS-Ta occurred 5 times more often than in women. According to two-stage logistic regression, the probability of irreversible event in men is 4,35 times higher than in women (p=0,0002). After adjusting for sex, in individuals with increased sQRS-Ta, it is 2,75 times higher than in individuals with sQRS-Ta <90o (p=0,015).Conclusion. In men with increased sQRS-Ta (≥90o), survival without irreversible and fatal cardiovascular events was worse, and life expectancy was shorter than in men with normal sQRS-Ta or women with increased sQRS-Ta. The prognosis of irreversible events was significantly affected by male sex and sQRS-Ta increase

Оценка риска метастазирования при проведении «прогностической» тонкоигольной аспирационной биопсии увеальной меланомы

Despite the widespread u se of fine-needle aspiration biopsy (FNAB) of uveal melanoma (UM) for prognostic purposes, there are still doubts about the safety of this procedure. No analysis of such data can be found in domestic literature, and foreign authors have published only a few papers on this issue.The purpose of this study is to analyze the risk of metastasis in patients with UM during FNAB.Two groups of patients were formed: the main group, where FNAB was performed during brachytherapy (BT) (BT + FNAB) (n = 70), and the control group, where only BT was performed (n = 144).According to the obtained data, the probability of metastases during a 3‑year follow-up period did not significantly differ between the two groups (p = 0.22 by Fisher's exact test and p = 0.11 by log-rank test when assessing survival using the Kaplan – Meier method), the relative risk (RR) was 1.43 [95 % CI 0.79 to 2.24]. In addition, there was no significant difference in the main clinical outcomes of local treatment associated with worse prognosis: the degree of tumor regression (p = 0.46), extrascleral growth, the need for additional brachytherapy (p = 0.32) or secondary enucleation (p = 0.99).The absence of a significant difference in patient survival between the BT and BT + FNAB groups opens up prospects for a more extensive use of FNAB in patients with UM for prognostic purposes.Аннотация: Несмотря на широкое использование тонкоигольной аспирационной биопсии (ТИАБ) увеальной меланомы (УМ) с прогностической целью, до сих пор высказываются сомнения в безопасности этой процедуры. При этом в отечественной литературе анализ таких данных не проводился, а среди зарубежных авторов по этой теме встречаются лишь единичные работы.Цель: проведение анализа риска метастазирования у пациентов с УМ при проведении ТИАБ.Были сформированы 2 группы пациентов: основная, где при проведении брахитерапии (БТ) одномоментно выполняли ТИАБ (БТ + ТИАБ) (n = 70), и контрольная, где проводилась только БТ (n = 144).Согласно полученным данным, вероятность возникновения метастазов в период 3‑летнего наблюдения в обеих группах не имеет статистически значимой разницы (p = 0,22 по точному критерию Фишера и p = 0,11 по логарифмическому ранговому критерию при оценке выживаемости методом Каплана – Майера), относительный риск (RR) составил 1,43 (95 % доверительный интервал от 0,79 до 2,24). Кроме того, не отмечалось статистически значимой разницы при оценке основных клинических исходов локального лечения, ассоциированных с ухудшением прогноза: степень регрессии опухоли (p = 0,46), экстрасклеральный рост, необходимость проведения дополнительной брахитерапии (p = 0,32) или вторичной энуклеации (p = 0,99).Отсутствие статистически значимой разницы в выживаемости пациентов в группах БТ и БТ + ТИАБ открывает перспективы для более масштабного применения ТИАБ у пациентов с УМ с прогностической целью

Комплексный анализ прогностической значимости аберраций хромосомы 8 у пациентов с увеальной меланомой

Introduction. Uveal melanoma ability to metastasize depends on a few prognostic factors. The genetic ones are considered to be the most significant. The role of disorders of the short arm of chromosome 8 (8p), as well as a combination of changes in 8p and the long arm of this chromosome (8q) in the development of metastatic lesions in this pathology remains insufficiently studied.The study objective – to evaluate the prognostic value of chromosome 8 abnormalities in patients with uveal melanoma.Materials and methods. We analyzed 2 retrospective groups of patients who underwent enucleation for uveal melanoma, statistically homogeneous in the main clinical parameters. Group 1 included patients without signs of metastases (n = 41) with an average follow-up period of 71 months, Group 2 included patients with detected metastases (n = 51) and an average follow-up period of 21 months Chromosome abnormalities were tested by multiplex ligation-dependent probe amplification.Results. Three- and five-year survival in patients with uveal melanoma without 8p deletion were 64 and 54 %, respectively; with 8p deletion significantly lower – 25 and 6 %, respectively. The same survival rates in patients with uveal melanoma with 8q amplification were 43 and 26 %, respectively, whereas in patients without 8q amplification they were significantly higher – 80 and 74 %, respectively. In patients with uveal melanoma harbouring both abnormalities, 3- and 5-year survival rates were 26 and 7 %, whereas isolated 8q amplification was associated with 47 and 35 % survival, respectively. These survival rates differ greatly and significantly: hazard ratio 3,26 (95 % confidence interval 1,86–5,69) and 6,89 (95 % confidence interval 2,67–17,73), respectively (р <0,0001).Conclusion. The findings support comprehensive evaluation of chromosome 8 abnormalities as a substantial part of uveal melanoma prognostication. 8q amplification, 8p deletion, combination of these abnormalities and its role in uveal melanoma malignity should be further discovered. Further research in this direction is needed.Введение. Способность увеальной меланомы к метастазированию зависит от целого спектра прогностических факторов, среди которых генетические имеют основополагающее значение. Роль нарушений короткого плеча хромосомы 8 (8р), а также комбинации изменений 8р и длинного плеча этой хромосомы (8q) в развитии метастатического поражения при данной патологии остается недостаточно изученной.Цель исследования – проведение комплексного анализа прогностической значимости аберраций хромосомы 8 у пациентов с увеальной меланомой.Материалы и методы. Были проанализированы 2 ретроспективные группы пациентов, которым была проведена энуклеация по поводу увеальной меланомы, статистически однородные по основным клиническим параметрам. В 1-ю группу вошли больные без признаков метастазов (n = 41) со средним сроком наблюдения 71 мес, во 2-ю группу – больные с выявленными метастазами (n = 51) и средним сроком наблюдения 21 мес. анализ хромосомных нарушений проводился методом мультиплексной амплификации лигированных зондов.Результаты. Трех- и 5-летняя выживаемость пациентов с увеальной меланомой без делеции 8p составила 64 и 54 %, с делецией 8p – 25 и 6 % соответственно. У больных с амплификацией 8q эти показатели были равны 43 и 26 %, у больных без амплификации 8q – 80 и 74 % соответственно. Для пациентов с одновременной амплификацией региона 8q и делецией региона 8р 3- и 5-летняя выживаемость составила 26 и 7 %, тогда как для пациентов с изолированной амплификацией 8q – 47 и 35 % соответственно. Уровень выживаемости пациентов с изолированной амплификацией 8q и комбинацией нарушений (del8p + amp8q) различается существенно и достоверно: отношение рисков 3,26 (95 % доверительный интервал 1,86–5,69) и 6,89 (95 % доверительный интервал 2,67–17,73) (р <0,0001).Заключение. Оценка амплификации 8q, делеции 8p и комбинации этих нарушений должна стать неотъемлемой частью прогнозирования риска метастазирования увеальной меланомы. Необходимы дальнейшие исследования в этом направлении

Анализ потребности пациентов с увеальной меланомой в индивидуальном прогнозировании риска метастазирования

Molecular-genetic study of uveal melanoma (UM) is crucial in predicting the risk of metastasis of this tumor. Such analysis is also possible during organ-sparing treatment based on fine-needle aspiration biopsy (FNAB), however, not all patients may consider this study appropriate and/or accessible.The goal of this study was to analyze the needs of patients with UM for individual metastasis risk prognosis.This retrospective cohort study was conducted using a questionnaire in 94 patients with UM (mean age 60 ± 13 years; 69 % women and 31 % men). Despite the rather high proportion of interested patients (77 %), only half (51 %) of them ultimately agreed to undergo a ”prognostic” FNAB, which was primarily due to the high cost of this study (it was the main reason for refusal in 76 % of cases). Patients were mainly motivated to know their risk by: a sense of control of the situation and the possibility of taking preventive measures (78 %), future planning for themselves and/or their loved ones (47 %), the possibility of participating in metastatic UM treatment programs (35 %), receiving the maximum amount of information about the disease (28 %). Patients without such intention cited a fear of revealing a high risk of metastases and an impossibility of psychological stabilization based on results of this test.Predicting the risk of metastasis is an important component of an integrated approach to the management of patients with uveal melanoma, including organ-sparing treatment. State funding of this study will increase the satisfaction of psychological needs in this category of cancer patients and improve understanding of the metastasis of uveal melanoma.Молекулярно-генетическое исследование увеальной меланомы (УМ) имеет решающее значение в прогнозировании риска метастазирования этой опухоли. Такой анализ возможен в том числе при проведении органосохраняющего лечения на материале тонкоигольной аспирационной биопсии (ТИАБ), однако не все пациенты могут считать данное исследование целесообразным и/или доступным.Цель: проведение анализа потребности пациентов с УМ в индивидуальном прогнозировании риска развития метастазов.Данное ретроспективное когортное исследование проводилось методом анкетирования 94 пациентов с УМ (средний возраст 60 ± 13 лет; 69 % женщин и 31 % мужчин).Несмотря на достаточно высокое число желающих (77 %), только половина (51 %) пациентов в конечном счете были согласны на проведение «прогностической» ТИАБ, что в первую очередь обусловлено высокой стоимостью данного исследования (в 76 % являлось основной причиной отказа). Среди основных мотивов желания знать риск отмечались следующие: ощущение контроля ситуации и возможность проведения профилактических мер (78 %), планирование дальнейшей жизни для себя и/или близких (47 %), возможность участия в программах лечения метастатической формы УМ (35 %), получение максимального количества информации о заболевании (28 %). Мотивы для отсутствия такого намерения связаны со страхом перед выявлением высокого риска развития метастазов и невозможностью стабилизации психологического состояния по результатам тестирования.Прогнозирование риска метастазирования опухоли является важной составляющей комплексного подхода в ведении пациентов с увеальной меланомой, в том числе при проведении органосохраняющего лечения. Возможность проведения данного исследования на бюджетной основе позволит повысить уровень удовлетворенности психологических потребностей у данной категории онкологических пациентов и улучшить понимание метастатических процессов увеальной меланомы