Lymphoepithelioma – a tumour rarely observed in children (3 cases)

Lymphoepithelioma rarely develops in children. In its early stage it may manifest itself only as enlarged cervical lymph nodes, which is likely to cause difficulties in the initial diagnosis. Radiotherapy is the treatment of choice, however, chemotherapy has also been used. The paper describes three cases of children treated for lymphoepithelioma at the Department of Children Hematology and Oncology in Lublin between 1991 – 2001. In all cases, the diagnosis was based on histopathological examinations of the tumour or lymph node biopsies. The methods of treatment used were different in each case and the longest disease free survival was 3 years. Therefore it seems necessary to design a uniform protocol of treatment for children with lymphoepithelioma.The first child was treated only to radiotherapy. This choice was based on lack of results of well conducted trials of cytostatic treatment. The good result of our treatment confirmed the data presented by other with the use of radiotherapy alone.In the second case, in case of large tumour, paralysis of cranial nerves, this patient was refered to combined treatment (radio-chemotherapy). In this case the partial remission was achived.In the third case, chemotherapy (cisplatin + 5-fluorouracil) resulted in perfect remission of the primary tumour and metastases to the lymph nodes while radiotherapy allow to achive complete control of the primary tumour and metastases to lymph nodes.     

Systems vaccinology: a promise for the young and the poor

As a child, the risk of suffering and dying from infection is higher the younger you are; and higher, the less developed a region you are born in. Childhood vaccination programmes have greatly reduced mortality around the world, but least so for the very young among the very poor of the world. This appears partly owing to suboptimal vaccine effectiveness. Unfortunately, although most vaccines are administered to the newborn and very young infant (less than or equal to two months), we know the least about their host response to vaccination. We thus currently lack the knowledge to guide efforts aimed at improving vaccine effectiveness in this vulnerable population. Systems vaccinology, the study of molecular networks activated by immunization, has begun to provide unprecedented insights into mechanisms leading to vaccine-induced protection from infection or disease. However, all published reports of systems vaccinology have focused on either adults or at most children and older infants, not those most in need, i.e. newborns and very young infants. Given that the tools of systems vaccinology work perfectly well with very small sample volumes, it is time we deliver the promise that systems vaccinology holds for those most in need of vaccine-mediated protection from infection.     

Radiotherapy in the treatment of Graves ophthalmopathy—to do it or not?

To the objective of this study is to evaluate the role and toxicity of radiotherapy in the treatment of Graves ophthalmopathy. In the years 2000–2003, 121 patients with malignant exophthalmos were treated with radiotherapy of the retrobulbar area to the total dose of 20 Gy in ten fractions with a 6 MeV photon beam. The treatment was performed by the team of the Clinic of Oncology of the Jagiellonian University Medical College in Cracow. The radiotherapy was preceded by intravenous steroid therapy: methylprednisolone acetate administered at the dose of 2 g/week for four consecutive weeks. The highest efficacy, expressed as improvement of all ocular symptoms, was observed for the combined treatment. Female and non-diabetic patients responded positively to the combined treatment. Radiotherapy combined with steroid therapy in the treatment of Graves ophthalmopathy seems to be an effective treatment for strictly defined indications. In the treatment of Graves–Basedow disease, radiotherapy is a well-tolerated treatment modality. Diabetes is a factor that worsens prognosis in Graves ophthalmopathy and female sex is a favourable factor for this condition.     

Radical radiotherapy for squamous cell carcinoma of the larynx - comparison of three-dimensional conformal radiotherapy with cobalt-60 teletherapy

(Full text is available at http://www.manu.edu.mk/prilozi). The aim of the study was to report the results of radical radiotherapy performed by three-dimensional conformal radiotherapy (3DCRT) for squamous cell carcinoma of the larynx and to compare these data with those obtained with two-dimensional radiotherapy (2DRT) realized with cobalt-60 teletherapy i.e. telecobalt therapy (TCT). Eighty patients with previously untreated laryngeal cancer were irradiated with curative intent at the University of Radiotherapy and Oncology Clinic (UCRO) in Skopje between February 1999 and December 2008. Radical radiotherapy with the TCT unit was performed on 38 patients between February 1999 and May 2005. From June 2005 to December 2008, 42 patients were treated with a linear accelerator using 3DCRT. Complete response rates three months after completion of radiotherapy were 84.2% (32 of 38) and 92.6% (39 of 42) in the group irradiated with TCT unit and in the group treated with 3DCRT, respectively. No statistically significant differences were observed either in locoregional control (LRC) or overall survival (OS) between the patients treated with two different radiotherapy techniques. The grade of acute reactions of the skin and the larynx differed significantly between the accomplished radiotherapy techniques (Nonparametric Mann-Whitney U Test; U = 577.0; Z = -2.129; p = 0.012, and U = 497.0; Z = -2.90; p = 0.001, respectively). There were statistically significant differences observed in the grade of late effects in the skin and in the subcutaneous tissue between the radiotherapy techniques used (Nonparametric Mann-Whitney U Test; U = 425.0; Z = -3.593; p = 0.001 and U = 637.0; Z = -1.551; p = 0.035, respectively). According to the confirmed advantage of 3DCRT in terms of reduced treatment toxicity observed in our study, we consider conformal techniques being a basis in definitive radiotherapy of squamous cell carcinoma of the larynx until the new revolutionary techniques will be clinically available. Key words: laryngeal cancer, radical radiotherapy, three-dimensional conformal radiotherapy, cobalt-60 teletherapy.     

Treatment results of childhood Hodgkin's lymphoma in Hungary

Lymphomas are the third most frequent malignancies in childhood. The Hungarian Pediatric Oncology Group was founded in 1971, and since then the same chemotherapeutic protocols have been used in the whole country. In this study we analyzed the data of childhood Hodgkin's lymphoma in Hungary in the last 11 years (1988-1998). We also compared our results with the international (German) data. The incidence of Hodgkin's lymphoma (0-15 years) was 7.1/1,000,000 child/year (the same for non-Hodgkin's lymphoma was 7.5/1,000,000/year); 5.5% of all pediatric malignancies in Hungary). The patients were treated according to the German DAL-HD-82 and 90 protocols. The therapy consisted of 2-6 cytostatic blocks, depending on the stage, followed by involved field irradiation. The overall survival was 94.7+/-2.0% at 5 years and 91.9+/-2.7% at 10 years. These results are very similar to the German data: 94% at 5 years and 93% at 10 years. The good results are due to the well organised network and the uniformed treatment. The results may be ameliorated by using autologous bone marrow transplantation.     

SinoDuplex: An Improved Duplex Sequencing Approach to Detect Low-frequency Variants in Plasma cfDNA Samples

Accurate detection of low frequency mutations from plasma cell-free DNA in blood using targeted next generation sequencing technology has shown promising benefits in clinical settings. Duplex sequencing technology is the most commonly used approach in liquid biopsies. Unique molecular identifiers are attached to each double-stranded DNA template, followed by production of low-error consensus sequences to detect low frequency variants. However, high sequencing costs have hindered application of this approach in clinical practice. Here, we have developed an improved duplex sequencing approach called Sino Duplex, which utilizes a pool of adapters containing pre-defined barcode sequences to generate far fewer barcode combinations than with random sequences, and implemented a novel computational analysis algorithm to generate duplex consensus sequences more precisely. Sino Duplex increased the output of duplex sequencing technology, making it more cost-effective. We evaluated our approach using reference standard samples and cell-free DNA samples from lung cancer patients. Our results showed that Sino Duplex has high sensitivity and specificity in detecting very low allele frequency mutations. The source code for Sino Duplex is freely available at https://github.com/Sin Oncology/sinoduplex.     

Application of GIS in epizootiological surveillance of swine trichinellosis in one endemic district in Serbia

Application of new tools for epizootiological investigations in veterinary medicine, such as Geographical Information Systems (GIS), offers a new approach and possibilities for the eradication or control of infectious diseases. GIS is particularly useful for research conducted in small areas strongly impacted by man. Trichinellosis is a world-wide zoonosis, which is endemic in some European countries, Balkan district and Serbia in particular. There are very few data on GIS application in the field of trichinellosis. We here present the application of GIS for mapping Trichinella spp. occurrence and spatial and temporal patterns of Trichinello infection in one endemic district in Serbia. Settlements with trichinellosis were marked and particular points of interest were designated. Data on prevalence of Trichinella infection in domestic swine accompanied by location of foci indicated the existence of disease geographical stationarity. This first report on GIS application in Serbia will facilitate trichinellosis surveillance and monitoring of Trichinella spp. circulation among domestic pigs, and populations of synanthropic and sylvatic animals.     

Cervical cancer screening in Serbia

Cervical cancer is the second most common female malignancy in Serbia, after breast cancer, with 1089 new registered cases and an age-standardized incidence rate of 27.2 per 100,000 women in 2002. It is the fourth leading cause of cancer death with 452 deaths and an age-standardized death rate of 7.2 per 100,000 women. Compared with other European countries, the incidence of cervical cancer in Central Serbia is the highest. Regional differences in incidence are pronounced in Serbia with the lowest age-standardized incidence rate (16.6 per 100,000 women) registered in the Macvanski region and the highest in eastern Serbia and the region of Belgrade where the rates are double at 32.5-38.1 per 100,000 women. Cervical cancer prevention in Serbia has relied on opportunistic screening that is characterized by high coverage in younger and low coverage in middle-aged and older women. Screening of selected groups of women employed in large companies is performed annually by many regional hospitals but this approach has little effect on morbidity and mortality. Recently, the Ministry of Health nominated an Expert Group to develop and implement a national cervical cancer screening program. A number of pilot projects have been undertaken with the results used for development of a national programme for cervical cancer screening. This is expected to be finalized in 2007, and launched over a 3-years period in order to cover all women aged 25-64 in entire Serbia.     

Extra-skeletal multiple myeloma presenting with an atrial mass: a case report and a review of the literature

ABSTRACT: INTRODUCTION: Extraskeletal presentation at diagnosis or during the course of multiple myeloma is a rareevent. The prognosis is usually very poor. At the moment there is no agreed gold standard forthe treatment of this presentation. CASE PRESENTATION: A 79-year-old Caucasian woman was treated at our hospital for right atrial myelomalocalization. Our patient showed the following signs and symptoms of congestive heartfailure: dyspnea, hypotension, cyanosis and facial edema. Surgery was not consideredfeasible due to the extent of the disease. Our patient underwent external-beam radiationtherapy using an intensity modulated technique, thus obtaining a persistent completeremission. Our patient has been in continuous complete local remission for 25 months sincethe end of radiotherapy. CONCLUSION: The role of radiotherapy is not defined in multiple myeloma with extraskeletal presentation.Our regimen seems to be effective in controlling the disease in this patient.This case report adds to the existing literature as it describes an unusual presentation of thedisease and a new therapeutic approach to this rare presentation of multiple myeloma.     

Parents’ posthumous use of daughter’s ovarian tissue: Ethical dimensions

In recent years, progress in cancer treatment has greatly increased the chances of recovery. Yet, treatment may have irreversible effects on patients’ fertility. In order to protect future fertility, preservation of ovarian tissue may be offered today even to very young girls, involving a surgical procedure that may be performed by minimally invasive laparoscopy, under general anesthesia. However, in the tragic event of a girl’s death, questions may arise regarding the possible use of the preserved ovarian tissue by her parents. Should posthumous reproductive use of ovarian tissue without the girl’s prior consent (due to her young age) be considered a violation of her rights? On the other hand, can it be argued that it is in the interest of a child who died young to leave a genetic trace through posthumous reproduction, because genetic continuity is in the interest of every human being? After presenting the relevant clinical facts, we explore the ethical dimensions of this possible practice through an analysis of the interests of the deceased, her parents, and the child that may be born posthumously.     

131I-MIBG therapy in the treatment of pheochromocytoma in children--own experiences

Three cases of pheochromocytoma in children/adolescents or young adults treated by 131I-MIBG are presented in this study. In one patient 131I-MIBG was administrated after ineffective surgical treatment and chemotherapy of a benign retroperitoneal tumor, whereas in two other patients 131I-MIBG therapy was carried out because of malignant pheochromocytoma dissemination. In a child with retroperitoneal paraganglioma decrease of tumor size and its fibrosis after 131I-MIBG therapy allowed radical surgery and complete recovery. In two other cases partial remission was achieved. All patients showed a good subjective response with improvement of the general condition and better blood pressure control. In two children adverse reactions such as leucopenia, hypothyroidism or hypogonadism were observed. The presented data confirm effectiveness and acceptable tolerance of 131I-MIBG treatment in pheochromocytoma, what is very important in pediatric patients.     

FLASH radiotherapy: an emerging approach in radiation therapy

FLASH radiotherapy (RT) is a technique involving the delivery of ultra-high dose rate radiation to the target. FLASH-RT has been shown to reduce radiation-induced toxicity in healthy tissues without compromising the anti-cancer effects of treatment compared to conventional radiation therapy. In the present article, we review the published data on FLASH-RT and discuss the current state of knowledge of this novel approach. We also highlight the technological constraints and complexity of FLASH-RT and describe the physics underlying this modality, particularly how technology supports energy transfer by ionising radiation (e.g., beam on/off sequence, pulse-energy load, intervals). We emphasise that current preclinical experience is mostly based on FLASH electrons and that clinical application of FLASH-RT is very limited. The incorporation of FLASH-RT into routine clinical radiotherapy will require the development of devices capable of producing FLASH photon beams.     

Angiosarcomas of the chest wall and breast after radiotherapy: The questions of radiogenic origin,diagnosis and treatment

PURPOSE: To present medical history of secondary chest wall and breast angiosarcomas (AS) developed after radiotherapy, and to discuss the questions of radiogenic origin, diagnosis and treatment by the review of the literature. METHODS: Report of two cases and MEDLINE search for relevant publications. RESULTS: Secondary AS occured in a previously irradiated field after a long (6 and 8 years) latency period in both cases. Detailed histopathological and immunohistochemical examinations from the biopsy and/or surgical specimens confirmed the diagnosis as AS. The first patient with moderately differentiated AS was treated successfully with radical surgery. The second patient with irresecable AS died of rapid local progression within 4 months. The incidence of chest wall and breast AS is increased after irradiation, however, controversial data exist in the literature. The incidence of chest wall and breast AS after radiotherapy was found to be 0.39% in our patient population, which means an estimated odds ratio of 2.4 for secondary AS. Stewart-Treves syndrome is not of radiogenic origin, since postoperative lymphoedema has been considered as primary etiological factor. CONCLUSIONS: Patients treated with surgery and/or radiotherapy for primary breast cancer are at higher risk for developing secondary AS, compared to the healthy population. An etiological relationship between radiotherapy and subsequent AS of chest wall and breast is likely, but still controversial. Initial radical surgery is the only effective treatment for achieving long term survival. Further adjuvant radiotherapy is no longer feasible, due to the previous irradiation. Chemotherapy has only palliative effect. These very rare cases deserve special attention due to the atypical clinical appearance, difficulties of differential diagnosis and poor prognosis.     

Stochastic modelling of the role of cisplatin in altered fractionation schedules for head and neck cancer

Advanced head and neck cancers are one of the most challenging cancers facing the oncologists due to their aggressiveness attributable to the high hypoxic content and the tumour's ability to repopulate during radiotherapy. Alterations of radiotherapy fractionation schedules are possible ways to improve tumour control. Clinical trials have shown that both hyperfractionated radiotherapy (multiple fractions a day, over the same treatment time), and accelerated radiotherapy (higher doses per fraction, six days a week, over 5 weeks or less) are more effective than conventional radiotherapy in the management of head and neck cancer. However, the treatment choice between hyperfractionated and accelerated radiotherapy is still debated, due to very similar results obtained regarding tumour control. Furthermore, while radiotherapy alone has an impact on the short-term prognosis of advanced head and neck cancer, the long-term benefits have been moderate. Cisplatin is a chemotherapeutic agent which combined with conventional radiotherapy has shown to improve patient survival. The present paper employs a Monte Carlo modelling approach in assessing the effect of combined cisplatin-altered fractionation schedule on tumour response. The growth of a head and neck carcinoma has been modelled using probabilistic functions sampled by computer generated random number sequences, maintaining the biological constitution of a tumour. The tumour growth model has been built to simulate the in vivo processes taking place before and after radiotherapy/chemotherapy. The model has shown that adding cisplatin to radiotherapy improves tumour control in both hyperfractionated and accelerated radiotherapy.     

Alkaline soda Lake Velika Rusanda (Serbia): the first insight into diatom diversity of this extreme saline lake

Alkaline soda lakes are unique habitats found in specific geographic regions, usually with dry climate. The Carpathian Basin is one of those regions very important for habitat and biodiversity conservation in Europe, with natural soda lakes found in Austria, Hungary and Serbia. In comparison to other two countries from Central Europe, algal biodiversity studies of saline soda lakes in Serbia are scarce. Lake Velika Rusanda has the highest measured salinity of all saline lakes in the Carpathian Basin and there were no reports of its diatom species richness and diversity till now. We conducted 2-year investigation programme to study biodiversity and seasonal dynamics of diatoms in this lake. A total of 27 diatom taxa were found, almost all of them attached to reed and much less in benthos and plankton. Five new diatom species for Serbia were recorded, Craticula halopannonica, Navicymbula pusilla, Hantzschia weyprechtii, Nitzschia thermaloides and Navicula staffordiae. The last mentioned is new for Europe as well. Lake Velika Rusanda is inhabited mostly by alkaliphilous and halophilic diatoms. Since diatoms are used as bioindicators in soda lakes, our results will improve their further application in ecological status assessment of these fragile habitats in the Carpathian Basin.

     

Haplotype reconstruction and estimation of haplotype frequencies from nuclear families with only one parent available

Recent literature has suggested that haplotype inference through close relatives, especially from nuclear families can be an alternative strategy in determining the linkage phase. In this paper, haplotype reconstruction and estimation of haplotype frequencies via expectation maximization (EM) algorithm including nuclear families with only one parent available is proposed. Parent and his (her) child are treated as parent-child pair with one shared haplotype. This reduces the number of potential haplotype pairs for both parent and child separately, resulting in a higher accuracy of the estimation. In a series of simulations, the comparisons of PHASE, GENEHUNTER, EM-based approach for complete nuclear families and our approach are carried out. In all situations, EM-based approach for trio data is comparable but slightly worse error rate than PHASE, our approach is slightly better and much faster than PHASE for incomplete trios, the performance of GENEHUNTER is very bad in simple nuclear family settings and dramatically decreased with the number of markers being increased. On the other hand, the comparison result of different sampling designs demonstrates that sampling trios is the most efficient design to estimate haplotype frequencies in populations under same genotyping cost.     

Primary malignant non-Hodgkin's lymphoma of the breast: a study of seven cases and literature review

ABSTRACT: INTRODUCTION: Primary breast lymphoma is an uncommon disease with poor clinical outcome. Breast lymphomas present less than 0.5% of malignant breast neoplasms and 2.2% of extranodal lymphomas. This study investigated the clinicopathological features and optimal treatment of PBL. Case presentations Clinical records of seven Moroccan PBL patients, treated at the National Institute of Oncology, Rabat, Morocco, from 2002 to 2010, were reviewed. Six of the patients were women and one a man, with ages ranging from 32 to 76. Five patients had stage IE and two stage IIE. All of the patients were classified with DLBCL. Of seven patients, one received a mastectomy and three excision of the breast lesion. Axillary dissection was performed in three patients. Two patients received chemotherapy followed by radiotherapy, while four received chemotherapy alone. Complete remission (CR) following primary treatment for all patients with PBL except in two cases was obtained. In one patient, recurrence occurred. CONCLUSIONS: There is no consensus on the question of how to best treat PBL: Mastectomy offers no benefit in the treatment of PBL. The combined therapy approach, with chemotherapy and radiotherapy, is the most successful treatment. PBL is poorly represented in rituximab-containing trials in DLBCL patients; there is not much experience with this agent in breast DLBCL. Because of the high incidence of central nervous system (CNS) involvement in PBL patients, many authors strongly believe that patients with aggressive forms of PBL should receive CNS infiltration prophylaxis.     

Inhibition of the amino‐acid transporter LAT1 demonstrates anti‐neoplastic activity in medulloblastoma

Most cases of medulloblastoma (MB) occur in young children. While the overall survival rate can be relatively high, current treatments combining surgery, chemo‐ and radiotherapy are very destructive for patient development and quality of life. Moreover, aggressive forms and recurrences of MB cannot be controlled by classical therapies. Therefore, new therapeutic approaches yielding good efficacy and low toxicity for healthy tissues are required to improve patient outcome. Cancer cells sustain their proliferation by optimizing their nutrient uptake capacities. The L‐type amino acid transporter 1 (LAT1) is an essential amino acid carrier overexpressed in aggressive human cancers that was described as a potential therapeutic target. In this study, we investigated the therapeutic potential of JPH203, a LAT1‐specific pharmacological inhibitor, on two independent MB cell lines belonging to subgroups 3 (HD‐MB03) and Shh (DAOY). We show that while displaying low toxicity towards normal cerebral cells, JPH203 disrupts AA homeostasis, mTORC1 activity, proliferation and survival in MB cells. Moreover, we demonstrate that a long‐term treatment with JPH203 does not lead to resistance in MB cells. Therefore, this study suggests that targeting LAT1 with JPH203 is a promising therapeutic approach for MB treatment.     

Protection gonadique contre les effets des chimiothérapies et/ou radiothérapies chez l'homme: applications cliniques

The damage effects of cytotoxic chemotherapy or radiotherapy were particularly important on spermatogenesis and fertility of young patients who were treated for cancer. The cryopresevation of semen is obligatory in these patients before starting therapy. In animals several protosols have been tried to protect the testis against chemotherapy and radiotherapy with positive results. In men, seven clinical trials have been done to preserve the testis by means of hormonal treatment. Five used GnRh agonist, one medroxyprogesterone acetate and the last one testosterone enanthate. These patients where treated with chemotherapy or/and radiotherapy. None of these clinical trials had any protective effect on testis function. The results of these studies, and the reasons of this failure are discussed, and, based on animals experiments and recent drogues availability new protosols of spermatogenesis preservation are suggested such as use of steroids, GnRh antagonist or testis hypothermia.     

The future of Radiation Oncology: Considerations of Young Medical Doctor

Radiation therapy plays an increasingly important role in the management of cancer. Currently, more than 50% of all cancer patients can expect to receive radiotherapy during the course of their disease, either in a primary management (radical or adjuvant radiotherapy) or for symptom control (palliative radiotherapy).Radiation oncology is a very unique branch of medicine connected with clinical knowledge and also with medical physics. In recent years, this approach has become increasingly absorbed with technological advances. This increasing emphasis on technology, together with other important changes in the health-care economic environment, now place the specialty of radiation oncology in a precarious position. New treatment technologies are evolving at a rate unprecedented in radiation therapy, paralleled by improvements in computer hardware and software. These techniques allow assessment of changes in the tumour volume and its location during the course of therapy (interfraction motion) so that re-planning can adjust for such changes in an adaptive radiotherapy process.If radiation oncologists become simply the guardians of a single therapeutic modality they may find that time marches by and, while the techniques will live on, the specialty may not. This article discusses these threats to the field and examines strategies by which we may evolve, diversify, and thrive.