OBJECTIVES: The aim of the study was to characterize subsequent neoplasm (SN) (malignant (SMN), benign (BSNs), and non-melanoma skin cancer (NMSC)) treated previously for a childhood solid malignant tumor at the Department of Pediatric Hematology and Oncology, Motol University Hospital, Prague. METHOD: We evaluated a cohort of 4059 childhood cancer survivors treated between 1975 and 2018. RESULTS: From 4059 survivors, 170 (4.3 %) developed at least one SMN - 193 SMNs in 170 survivors, 21 of them (0.5 % of all survivors) had two or more SMNs and 34 of them (0.8 %) had one SMN and one or more BSNs. Mortality for an SMN was 38.2 % i.e. 1.6 % of all survivors. The most frequent SMNs were thyroid carcinoma (37, 19.2 %), tumors of the central nervous system (25, 13.0 %), soft tissue sarcoma (23, 11.9 %), breast carcinoma (19, 9.8 %), and leukemia (11, 5.7 %). Genetic syndromes were present in 25 patients with SMNs (14.7 %) and in 16 patients with only BSNs (13.4 %). SMNs usually developed in second decade or later after finishing of therapy. We observed some not well known risk factors of SNs e.g. spinal irradiation or131-I metaiodobenzylguanidine radiotherapy in 2 cases of secondary thyroid cancer, cyclophosphamide therapy in all 8 cases of secondary urinary bladder sarcoma or 4 from 7 SNMSC developed SMN. CONCLUSIONS: We confirmed data from previous studies of SNs and observed some not so well known risk factors. Our results and the literature show that the incidence of SMNs is 3-10 % of survivors and is associated with high mortality.

• Klíčová slova
• Genetic syndromes with increased risk of cancer, Long-term childhood cancer survivors, Subsequent benign neoplasm, Subsequent malignant neoplasm, Subsequent non-melanoma skin cancer,
• MeSH
• dítě MeSH
• dospělí MeSH
• incidence MeSH
• kohortové studie MeSH
• lidé MeSH
• míra přežití MeSH
• mladiství MeSH
• nádory komplikace   patologie   terapie   MeSH
• přežívající onkologičtí pacienti statistika a číselné údaje   MeSH
• prognóza MeSH
• rizikové faktory MeSH
• sekundární malignity epidemiologie   etiologie   patologie   MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Česká republika epidemiologie   MeSH

BACKGROUND: The principal aim of this report was to study second primary malignant neoplasms (SMNs) in long-term survivors of pancreatic ductal adenocarcinoma (PDAC) with regard to the germline genetic background. PATIENTS AND METHODS: A total of 118 PDAC patients after a curative-intent surgery who were treated between 2006 and 2011 were analyzed. Of the 22 patients surviving for >5 years, six went on to develop SMNs. A genetic analysis of 219 hereditary cancer-predisposition and candidate genes was performed by targeted next-generation sequencing in germline DNA from 20 of these patients. RESULTS: Of all the radically resected PDAC patients, six patients went on to subsequently develop SMNs, which accounted for 27% of the long-term survivors. The median time to diagnosis of SMNs, which included two cases of rectal cancer, and one case each of prostate cancer, malignant melanoma, breast cancer, and urinary bladder cancer, was 52.5 months. At the time of analysis, none of these patients had died as a result of PDAC progression. We identified four carriers of germline pathogenic mutations in 20 analyzed long-term survivors. One carrier of the CHEK2 mutation was found among four analyzed patients who developed SMNs. Of the remaining 16 long-term PDAC survivors, 3 patients (19%) carried germline mutation(s) in the MLH1+ ATM, CHEK2, and RAD51D gene, respectively. CONCLUSION: This retrospective analysis indicates that SMNs in PDAC survivors are an important clinical problem and may be more common than has been acknowledged to be the case. In patients with good performance status, surgical therapy should be considered, as the SMNs often have a favorable prognosis.

• Klíčová slova
• hereditary cancer genes, long-term survivors, pancreatic ductal adenocarcinoma, second primary neoplasms, subsequent malignant neoplasm, surgical treatment,
• Publikační typ
• časopisecké články MeSH

Advances in medicine have improved outcomes in children diagnosed with cancer, with overall 5-year survival rates for these children now exceeding 80%. Two-thirds of childhood cancer survivors have at least one late effect of cancer therapy, with one-third having serious or even life-threatening effects. One of the most serious late effects is a development of subsequent malignant neoplasms (histologically different cancers, which appear after the treatment for primary cancer), which occur in about 3-10% of survivors and are associated with high mortality. In cancers with a very good prognosis, subsequent malignant neoplasms significantly affect long-term survival. Therefore, there is an effort to reduce particularly hazardous treatments. This review discusses the importance of individual factors (gender, genetic factors, cytostatic drugs, radiotherapy) in the development of subsequent malignant neoplasms and the possibilities of their prediction and prevention in the future.

• Klíčová slova
• cancer predisposition syndromes, chemotherapy, childhood cancer survivors, genetic factors, radiotherapy, subsequent malignant neoplasms,
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

BACKGROUND: Numbers of patients who develop subsequent primary tumours have markedly increased recently. This study aimed to carry out a comprehensive analysis documenting the risk of incidence of subsequent haematological malignancies. METHODS: The Czech National Cancer Registry was the main data source, containing records of 126,822 haematological malignancies diagnosed in the period 1977-2016. Subsequent haematological malignancies were identified according to IACR rules. Joinpoint regression was employed to assess the time trends. The risk of development of subsequent haematological malignancy was evaluated by the standardised incidence ratio. The Kaplan-Meier curves were used to assess the differences in survival. RESULTS: Age-standardised incidence of subsequent haematological malignancies increased from 0.5 in 1977 to 9.1 in 2016. In 1992, there was a significant change in the trend: a sharp increase by 7.7 % annually was revealed thereafter. The risk of development of a haematological malignancy was approximately 1.5 times higher in persons with history of any cancer than in the general Czech population. Patients with haematological malignancies - mainly myelodysplastic syndromes, polycythaemia vera and non-Hodgkin lymphoma - were shown to be at the highest risk of developing a subsequent haematological malignancy. While the median survival following a first haematological malignancy was 2.3 years, it was only 1.1 years for subsequent haematological malignancies (p < 0.001). CONCLUSIONS: Our study identified the highest-risk diagnoses in terms of development of subsequent haematological malignancy. The results might be useful to set up correctly follow-up procedures from which cancer patients could benefit.

• Klíčová slova
• Haematological malignancies, Standardised incidence ratio, Subsequent primary tumour, Survival, Time trends,
• MeSH
• hematologické nádory epidemiologie   terapie   MeSH
• hodnocení rizik MeSH
• incidence MeSH
• lidé MeSH
• registrace MeSH
• sekundární malignity epidemiologie   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: Papillary urothelial neoplasm of low malignant potential (PUN-LMP) was introduced as a noninvasive, noncancerous lesion and a separate grade category in 1998. Subsequently, PUN-LMP was reconfirmed by World Health Organization (WHO) 2004 and WHO 2016 classifications for urothelial bladder tumors. OBJECTIVES: To analyze the proportion of PUN-LMP diagnosis over time and to determine its prognostic value compared to Ta-LG (low-grade) and Ta-HG (high-grade) carcinomas. To assess the intraobserver variability of an experienced uropathologist assigning (WHO) 2004/2016 grades at 2 time points. MATERIALS AND METHODS: Individual patient data of 3,311 primary Ta bladder tumors from 17 hospitals in Europe and Canada were available. Transurethral resection of the tumor was performed between 1990 and 2018. Time to recurrence and progression were analyzed with cumulative incidence functions, log-rank tests and multivariable Cox-regression stratified by institution. Intraobserver variability was assessed by examining the same 314 transurethral resection of the tumorslides twice, in 2004 and again in 2018. RESULTS: PUN-LMP represented 3.8% (127/3,311) of Ta tumors. The same pathologist found 71/314 (22.6%) PUN-LMPs in 2004 and only 20/314 (6.4%) in 2018. Overall, the proportion of PUN-LMP diagnosis substantially decreased over time from 31.3% (1990-2000) to 3.2% (2000-2010) and to 1.1% (2010-2018). We found no difference in time to recurrence between the three WHO 2004/2016 Ta-grade categories (log-rank, P = 0.381), nor for LG vs. PUN-LMP (log-rank, P = 0.238). Time to progression was different for all grade categories (log-rank, P < 0.001), but not between LG and PUN-LMP (log-rank, P = 0.096). Multivariable analyses on recurrence and progression showed similar results for all 3 grade categories and for LG vs. PUN-LMP. CONCLUSIONS: The proportion of PUN-LMP has decreased to very low levels in the last decade. Contrary to its reconfirmation in the WHO 2016 classification, our results do not support the continued use of PUN-LMP as a separate grade category in Ta tumors because of the similar prognosis for PUN-LMP and Ta-LG carcinomas.

• Klíčová slova
• Bladder, Cancer, Carcinomas, Grade, Nonmuscle-invasive, Urothelial, WHO,
• MeSH
• invazivní růst nádoru MeSH
• karcinom z přechodných buněk patologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• lokální recidiva nádoru epidemiologie   MeSH
• nádory močového měchýře patologie   MeSH
• odchylka pozorovatele MeSH
• papilární karcinom patologie   MeSH
• retrospektivní studie MeSH
• senioři MeSH
• stupeň nádoru MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• Geografické názvy
• Evropa MeSH
• Kanada MeSH

BACKGROUND: Soft-tissue sarcomas are rare tumors with the incidence of multiple metachronous or synchronous lesions in the extremities being even more uncommon. In effort to preserve the function of upper extremities, limb-salvage surgery became the treatment of choice for soft-tissue sarcomas. Subsequent adjuvant chemotherapy, as well as radiotherapy, is believed to decrease local recurrence rates, however, their effect on overall survival remains unclear. CASE: We report herein a case of symmetrical bilateral metachronous malignant fibrous histiocytomas of the shoulder. A 19-year-old patient presented with stiffness and pain in the right shoulder. The same symptoms developed 1.5 years later in the other shoulder. The culprit tumors are reported metachronous with regard to the succession in the onset of symptoms. Wide tumor resection was performed in both shoulders, and postoperative radiotherapy was then conducted. Chemotherapy was not indicated after the first surgery; whereas, in the second case it was the patient who refused the recommended adjuvant chemotherapy. CONCLUSION: The phenomenon of either metachronous or synchronous incidence of multiple soft tissue sarcomas is very rare and systematic reporting of every new case in the literature could contribute to further knowledge of tumors unique behavior.Key words: malignant fibrous histiocytoma - radiotherapy - upper extremity - neoplasms - multiple primary.

• MeSH
• lidé MeSH
• magnetická rezonanční tomografie MeSH
• maligní fibrózní histiocytom diagnóza   terapie   MeSH
• mladý dospělý MeSH
• rameno MeSH
• sarkom diagnóza   terapie   MeSH
• sekundární malignity diagnóza   terapie   MeSH
• Check Tag
• lidé MeSH
• mladý dospělý MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH

• MeSH
• analýza přežití MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádory štítné žlázy komplikace   chirurgie   MeSH
• retrospektivní studie MeSH
• struma komplikace   chirurgie   MeSH
• tyreoidektomie * MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: A number of studies have reported that the xeroderma pigmentosum complementation group C (XPC) polymorphisms are associated with cutaneous malignant melanoma (CMM) susceptibility. But the results of those studies were inconsistent. Here, we performed a study to obtain a more conclusive result on the association of XPC polymorphisms with risk of CMM. METHODS: The XPC Lys939Gln and Ala499Val polymorphisms were genotyped in 150 CMM cases and 150 controls by PCR-RFLP assay. Subsequently, all published relevant studies were identified through a comprehensive literature search in PubMed, Web of Science, and CNKI databases. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to estimate the strength of correlation. RESULTS: There was no significant association between XPC Lys939Gln and Ala499Val polymorphisms and CMM risk in our population. A total of 15 case-control studies including ten studies with 5,990 cases and 7,697 controls on XPC Lys939Gln and five studies with 3,139 cases and 3,721 controls on XPC Ala499Val polymorphism were selected. Pooled data revealed that XPC Lys939Gln (C vs. A: OR = 1.108, 95% CI 1.008- 1.217; P = 0.033) and Ala499Val (C vs. A: OR = 0.918, 95% CI 0.850-0.992; p = 0.031; CC+CA vs. AA: OR = 0.904, 95% CI 0.819-0.997; p = 0.043) polymorphisms were significantly associated with an increased risk of CMM. Moreover, stratified analyses by ethnicity revealed that the XPC Ala499Val and Lys939Gln polymorphisms were significantly associated with risk of CMM in Caucasians and mixed populations, respectively. CONCLUSIONS: This meta-analysis result suggested that XPC Lys939Gln and Ala499Val polymorphisms were significantly associated with risk of CMM.

• Klíčová slova
• XPC gene, cutaneous melanoma, malignant melanoma, meta-analysis, polymorphism,
• MeSH
• DNA vazebné proteiny genetika   MeSH
• genetická predispozice k nemoci MeSH
• hodnocení rizik statistika a číselné údaje   MeSH
• jednonukleotidový polymorfismus MeSH
• lidé MeSH
• maligní melanom kůže MeSH
• melanom genetika   MeSH
• nádory kůže genetika   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• metaanalýza MeSH
• Názvy látek
• DNA vazebné proteiny MeSH
• XPC protein, human MeSH Prohlížeč

BACKGROUND: Glioblastoma is a malignant and aggressive type of central nevous system malignancy characterized by many distinct biological features including extensive hypoxia. Hypoxia in glioblatoma associates with complex signaling patterns including activation of several pathways such as MAPK, PI3K-AKT/mTOR and IL-6/JAK/STAT3 with the master regulator HIF-1, which in turn drive particular tumor behaviors determining, in the end, treatment outcomes and patients fate. Thus, the present study was designed to investigate the expression of selected hypoxia related factors including STAT3 in a small set of long-term surviving glioma patients. METHODS: The expression of selected hypoxia related factors including STAT3 was evaluated in a time series of formalin fixed paraffin embedded and cryopreserved glioma samples from repeatedly resected patients. In addition, comparative studies were also conducted on primary glioma cells derived from original patient samples, stabilized glioma cell lines and tumor-xenograft mice model. Obtained data were correlated with clinical findings too. RESULTS: Glioblastoma samples of the analyzed patients displayed heterogeneity in the expression of hypoxia- related and EMT markers with most interesting trend being observed in pSTAT3. This heterogeneity was subsequently confirmed in other employed models (primocultures derived from glioblastoma tissue resections, cryopreserved tumor specimens, stabilized glioblastoma cell line in vitro and in vivo) and concerned, in particular, STAT3 expression which remained stable. In addition, subsequent studies on the role of STAT3 in the context of glioblastoma hypoxia demonstrated opposing effects of its deletion on cell viability as well as the expression of hypoxia and EMT markers. CONCLUSIONS: Our results suport the importance of STAT3 expression and activity in the context of hypoxia in malignant glioblastoma long-term surviving glioma patients while emphasizing heterogeneity of biological outcomes in varying employed tumor models.

• Klíčová slova
• Glioblastoma, Hypoxia, Long-surviving patients, Primocultures, STAT3, Temozolomide,
• MeSH
• dospělí MeSH
• glioblastom metabolismus   patologie   genetika   MeSH
• gliom * metabolismus   patologie   genetika   MeSH
• hypoxie metabolismus   MeSH
• lidé středního věku MeSH
• lidé MeSH
• myši MeSH
• nádorové biomarkery metabolismus   MeSH
• nádorové buněčné linie MeSH
• nádory mozku metabolismus   patologie   genetika   MeSH
• regulace genové exprese u nádorů MeSH
• senioři MeSH
• transkripční faktor STAT3 * metabolismus   MeSH
• zvířata MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• myši MeSH
• senioři MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• nádorové biomarkery MeSH
• STAT3 protein, human MeSH Prohlížeč
• transkripční faktor STAT3 * MeSH

PURPOSE: Mastectomy without axillary dissection should be the standard treatment in patients with malignant form of cystosarcoma phyllodes. The role of postoperative radiotherapy and chemotherapy remains to be fully established. We evaluate treatment results in a group of patients with cystosarcoma phyllodes (CP) treated at our Institute. PATIENTS AND METHODS: In this report we analyze treatment outcome in 25 patients with malignant cystosarcoma phyllodes treated at Masaryk Memorial Cancer Institute between 1970 and 1995. Mean tumor size was 10 cm in diameter. All patients underwent surgery. Subsequently, 17 patients (68%) received radiotherapy on the breast or chest wall. RESULTS: Median follow-up was 139.5 months. Local recurrence was observed in 16% of all patients and all patients with local recurrence died. Time to local relapse after surgery was 4-11 months. Distant metastases occurred in 5 patients. All patients with local recurrence had distant metastases. Dissemination occurred 3-19 months after local recurrence. Five-year survival of all patients was 80%. CONCLUSION: A specific protocol for the treatment of cystosarcoma phyllodes is missing, probably due to rarity of the disease. The treatment of local recurrent disease remains unsuccessful in most CP patients. We recommend postoperative irradiation on the chest wall in patients with malignant form of CP, because adjuvant radiotherapy decreased the incidence of local relapse in our group of patients.

• MeSH
• analýza přežití MeSH
• chorobopisy MeSH
• cystosarcoma phyllodes diagnóza   epidemiologie   etiologie   patologie   terapie   MeSH
• dospělí MeSH
• kombinovaná terapie MeSH
• lidé středního věku MeSH
• lidé MeSH
• lokální recidiva nádoru diagnóza   epidemiologie   etiologie   patologie   terapie   MeSH
• nádory prsu diagnóza   epidemiologie   etiologie   patologie   terapie   MeSH
• přežití po terapii bez příznaků nemoci MeSH
• retrospektivní studie MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika epidemiologie   MeSH