Biomedical subjects
Publications and source records attributed to Andrzej Kurylak.
The authors present the case of a 17-year-old girl, with pain over lumbar spine area, treated by paediatricians and rehabilitation specialists, discussing diagnostic imaging and laboratory examinations together with clinical observations. Spondylodiscitis was diagnosed after bone scintigraphy with 99mTc-MDP, the course of disease was monitored by immunoscintigraphy amongst other techniques.
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Clear statement that pediatric neoplasms are really rare is not easy. Thus the incidence of rare tumours in children has not been defined so far. The paper efforts to assess the topic of rare tumours of childhood in the Polish population. Following two categories are proposed: tumours typical for adults, but possible in children (neoplasms of epithelial origin--mainly carcinomas, melanomas, carcinoids) and paediatric tumours consisting less than 10% of cases in corresponding clinical groups according to the ICCC classification. Data on 317 patients aged 0-18 years treated in centres associated in the Polish Paediatric Group for Solid Tumours (PPGST) were analysed. Classical adult malignancies were registered in 130 patients: carcinomas in 90 (mean age 12.6 +/- 4.5 years), melanomas in 25 (mean age 9.4 +/- 4.9) and carcinoids in 9 (mean age 14.5 +/- 1.2 years). Non epithelial neoplasms were registered in 187 patients (mean age 10.4 +/- 5.5). That group included rare tumours of soft tissue, CNS, bones and other organs. Treatments of certain groups were specified by separate therapeutic protocols within PPGST. Rare malignancies of adult-type among children under 18 years of age in Poland comprised 1.5% of all pediatric neoplasms. The incidence of adult-type neoplasms increased with age until 14 years. In patients over 15 years of age the number of registered cases decreased. It may suggest a first peak of incidence in early adolescence or an underestimation of number of patients with carcinoma aged over 15 years. In the analyzed group, the mean age of patients with carcinomas and other epithelial and unspecified tumours significantly exceeded the age of children with rare neoplasms of non-epithelial origin (12.1 +/- 4.7 vs 10.4 +/- 5.5 years; p<0.05). A very young age at diagnosis of malignant melanomas (mean 9.4 years) and numerous cases of carcinomas affecting the digestive tract (n=24; 27% of all carcinomas), especially those located in colorectal region (n=10), seem surprising. The preliminary analysis of the collected data on rare neoplasms in Poland encourage to undertake a prospective study, meant to link the epidemiology and characteristics of rare epithelial tumours in childhood with diagnostic and therapeutic suggestions for these types that are not coordinated within Polish Paediatric Group of Solid Tumours.
The study has been evaluated an efficiency of preventive use of hematopoietic cytokines in children with neoplastic diseases. The analysed material consisted of 28 children with neoplastic diseases. They all had 148 incidents of chemotherapy-induced myelosuppression with prophylactic use of GM-CSF or G-CSF 5 micrograms/kg daily. The study showed that the prophylactic use of hematopoietic growth factors after the end of each chemotherapy course significantly shortens the duration of extreme neutropenia, the length of treatment of neutropenia-induced infections, the time of hospital care and decreases the delay between succeeding chemotherapy courses.
Uptake and efflux of two anthracyclines, idarubicin (IDA) and daunorubicin (DNR), was studied in childhood acute leukemia samples. A comparison of IDA and DNR transport phenomena in relation to drug cytotoxicity and expression of P-glycoprotein (PGP) was made. Intracellular content of IDA/DNR was determined by flow cytometry using the fluorescent properties of the drugs. In vitro drug cytotoxicity was measured by the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) assay. PGP expression was analysed by flow cytometry. The uptake and efflux rates were non-significantly higher for IDA than DNR. There were no differences between three types of leukemia with respect to drug content during accumulation and retention. After correction for the cell volume, intracellular concentration of both drugs in each moment of uptake and efflux was significantly lower in relapsed ALL and AML samples in comparison with initial ALL cells. Efflux, but not uptake, of both drugs was inversely correlated with PGP expression and IDA, but not DNR, cytotoxicity. The cytotoxicity was correlated with drug accumulation for both drugs and with drug retention for IDA. In conclusion, it seems that (1) intracellular content was related to the lipophilic properties of the drugs rather than to the type of leukemia, (2) decreased intracellular concentration of both drugs might have an impact on compromised therapy results in AML and relapsed ALL children, (3) IDA presents higher cytotoxicity, which possibly might be decreased by the presence of PGP. These results might have a practical impact on the rational design of new chemotherapy protocols.
Glufosfamide is a new agent for cancer chemotherapy. The objective of the study was the comparison of the in vitro drug resistance profile of glufosfamide with other oxazaphosphorines in 106 samples of childhood acute leukemia by means of the MTT assay. The following drugs were tested: glufosfamide, 4-HOO-ifosfamide, 4-HOO-cyclophosphamide, mafosfamide cyclohexylamine salt, prednisolone, vincristine, L-asparaginase, daunorubicin and cytarabine. In the group of initial Acute Lymphoblastic Leukemia (ALL) samples, equivalent cytotoxicity values for glufosfamide, 4-HOO-ifosfamide, 4-HOO-cyclophosphamide and mafosfamide were 5.95, 9.92, 4.60 and 3.90 microg/ml, respectively. In comparison to initial ALL samples, the relative resistance for glufosfamide and 4-HOO-ifosfamide in relapsed ALL samples were 1.9 (p=0.049) and 1.3 (ns), and in initial Acute Myeloblastic Leukemia (AML) samples, respectively, 31 (p<0.001) and 5 (p=0.001). All oxazaphosphorines showed highly significant cross-resistance. In conclusion, in vitro activity of glufosfamide is comparable to ifosfamide. Glufosfamide shows high activity against lymphoblasts both on diagnosis and on relapse, however it cannot circumvent resistance to other oxazaphosphorines.
UNLABELLED: Malignant vascular tumours represent a rare group of neoplasms, usually treated according to protocols for soft tissue sarcomas. THE AIM OF THE STUDY: To assess the clinical characteristics, disease course and outcome in Polish children with malignant vascular neoplasms. MATERIAL AND METHODS: The Polish Paediatric Rare Tumours Study retrospectively analysed multicentre data on 32 children with vascular tumours, registered between 1992 and 2002. On the basis of the histological type of the neoplasm these patients have been divided into three groups: group I -- 10 patients with angiosarcoma (ASA), group II -- 7 children with haemangioendothelioma (HE) and group III- 15 patients with haemangiopericytoma (HP), of both infantile (7 children) and adult-types (8 patients). RESULTS: Group I: 5 patients presented with local, 3 with systemic and 2 with regional disease. Primary complete resection (PRC) was performed in 7 patients, not resulting in local control in any of them. Radiotherapy (RTX) was administered in 5 patients, chemotherapy (CHT) in all. 7 patients relapsed, 3 never entered clinical remission. 9 of the 10 patients of group I, died of disease progression. Group II: PRC was performed in 5 patients and led to local control in 2. Adjuvant RTX was used in 2 and CHT in 4 patients. 2 children relapsed and died of the disease. Infantile HP: PRC was performed in 3 children, remaining 4 patients received adjuvant CHT All children entered complete remission and are disease-free. Adult-type HP: PRC was performed in 5 patients, resulting in local control in 4. Five children were given adjuvant RTX and six CHT Three patients relapsed and died of disease progression. CONCLUSIONS: The effectiveness of primary complete resection in all groups was doubtful. The high rate of metastatic relapses suggests that the currently given systemic therapy is not satisfactory. The only tumour with excellent prognosis was infantile type HP (all patients are alive and free of disease). Adequate treatment for children with angiosarcoma remains still unknown -- 9 of 10 patients died of disease progression. Prognosis in patients with haemangioendothelioma is intermediate, however the role of immunotherapy should be further investigated.
Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children younger then 15 years of age. The treatment of RMS localized in bladder or prostate still remains controversial. The aim of this study was analysis of treatment results in children with soft tissue sarcoma of bladder and prostate. From 1993 to 2001 the PPSTG has used three protocols to treat soft tissue sarcomas in children. The CWS-91 regimen has been served to treat stage I-III and SIOP-IV Intergroup study in stage IV. Since 1996 the CWS-96 protocol for all patients in stage I-IV has been used. After biopsy confirmation of the diagnosis patients were treated with chemotherapy and subsequent surgery. Radiotherapy was administrated with total dose 32Gy v 44.5Gy v 48Gy. The group of 19 patients aged from 3 months to 18 years with median age 6 y 4 m were evaluated. The median follow-up time was 42 months. RMS-embryonal was diagnosed in 11 patients, RMS-alveolare in 4 and others types in 4. Sixteen patients presented clinical stage III and 3 stage IV The tumours were primarily localised in bladder in 16 patients and prostate in 3. Eight were tumours of volume bigger than 10 cm. After induction chemotherapy two patients received partial cystectomy, 5 complete cystectomy and 3 complete cystectomy with genitourinary reconstructive. Eight patients did not receive surgery. The most common treatment failure was isolated, local relapse in 8 children particularly in patients with any second surgery. The EFS for all patients was 52% and for patients with localised RMS tumours 65%. Significant prognostic factors are the initial tumours volume, the lymph nodes infiltration and the response to the first chemotherapy cycle. Surgery is the most important procedure in local control of soft tissue sarcoma. Reconstructive options in poor and non responder patients can improve the EFS and life quality of those patients.
BACKGROUND: Glucocorticoids are the most important group of drugs used in the treatment of childhood acute lymphoblastic leukemia (ALL), however, resistance to this group remains the main obstacle in curing the disease. One of the possibilities to circumvent glucocorticoid resistance is the use of new compounds, such as cortivazol (CVZ), which has two binding sites for the glucocorticoid receptor. AIM: Analysis of ex vivo sensitivity to cortivazol and other glucocorticoids in childhood acute lymphoblastic leukemia, as well as the relationship to anticancer therapy outcome. PATIENTS AND METHODS: Leukemic samples from 60 children with ALL were tested by the M7T assay for glucocorticoid resistance. Cell cycle before and after ex vivo glucocorticoid treatment was analyzed by flow cytometry. RESULTS: Although all tested glucocorticoids presented significant cross-resistance, CVZ showed high antileukemic activity. The equivalent activity of CVZ was 165-fold higher than prednisolone, 7.ZS5-fold higher than dexamethasone and 2.8-fold higher than betamethasone. CVZ showed relatively better cytotoxicity than other glucocorticoids in prednisolone-poor-responders. CVZ, like other glucocorticoids, caused cell cycle arrest in the GI-phase, and increased the percentage of apoptotic cells to a greater extent than other glucocorticoids. The results of antileukemic therapy were strongly related to the ex vivo resistance to all tested glucocorticoids. CONCLUSION: Cortivazol has potent antileukemic activity in childhood ALL. Its activity is related to cell cycle arrest and induction of apoptosis.
AIM: analysis of the course, outcome and therapy complications in bladder/prostate soft tissue sarcomas (STS) in children treated from I'1997 to II'2003 according to CWS-96 protocol in Poland. MATERIAL AND METHODS: 22 children (M/F: 17/5, age: 8 months - 17 years 2 months; median 5,3y). Histopathology: RMS-20 patients (RME-14), non-RMS-2 patients. RESULTS: 96% presented with advanced neoplasm (III - 14, IV - 7). In 18 patients (82%) primary tumour exceeded 5cm; in 17 (77%) extended beyond site of origin. Lymph nodes metastases were stated in six (27%), distant metastases in seven patients (32%). No patient underwent primary complete tumour excision. All received chemotherapy for high risk group. Response to chemotherapy after three cycles was favourable in eight and unfavourable in eight children. Delayed resections were performed in 11 patients (mutilating - 7) proving complete in only five. Radiotherapy (32-50,4Gy) was given to 16 patients, mainly after delayed incomplete surgery. Five patients developed local relapse, four--continual disease progression. None of these nine patients had ever complete tumour resection. Nine patients died: seven due to neoplasm progression, two of therapy complications (septic shock, ARDS). Thirteen patients are alive (59%) with mean follow-up of 42 months. Eight children had bladder removed with continent ileal pouch formed in four. CONCLUSIONS: 1) Advanced stages of bladder/prostate sarcomas in children suggest the necessity of earlier diagnosis. 2) Due to adjuvant chemo- and radiotherapy approximately 60% of patients with this diagnosis may be nowadays cured of bladder/prostate sarcomas without mutilating surgical procedures.
AIM: Analysis of therapy efficacy in non-bladder/prostate genitourinary sarcomas in children treated from I'1997 to VI'2003 with CWS-96 protocol in Poland. MATERIAL AND METHODS: 19 children (M/F: 15/4, age: 3m-17,5y; median 7,2y). Histopathology: RMS - 15pts (RME-13), non-RMS- 4. RESULTS: Primary site: testes - 9 patients, paratesticular region - 6, uterus - 2, vagina and ovary-1 of each. 63% presented with low stage neoplasm (I - 7, II - 5). Primary tumour exceeded 5cm and/or invaded surrounding tissues in 7 patients (37%). 3 patients had regional, 2 patients--distant lymph nodes metastases. Primary excision: complete in 7 patients, incomplete - 12 (microscopically - 5, macroscopically - 7). Six of 7 patients with macroscopic tumour residues responded to chemotherapy (CR-4, GR-2). One patient (stage III triton tumour of uterus) did not, respond but obtained complete remission after mutilating delayed surgery. No other patient required delayed tumour resection. Radiotherapy (23,5-54 Gy) was given to 8 patients. 3 children developed local relapse, 3 patients died (16%): 2 due to neoplasm progression, 1 of neutropenia-related sepsis. 16 patients are alive (84%) with mean follow-up 48 months. The only permanent complications result from mutilating surgery. CONCLUSIONS: 1) prognosis in children with non-bladder/prostate genitourinary sarcomas is favourable despite incomplete primary excision of the neoplasm. 2) chemotherapy and radiotherapy were accompanied by severe but transient myelosupression in the HR group.