<p>Uprkos postojanju dijagnostičkih procedura za ranu dijagnostiku, sprovođenju preventivnog skrining programa, te dugom preinvazivnom periodu u kojem je moguće izvr&scaron;iti detekciju, karcinom grlića materice i dalje predstavlja jedan od vodećih zdravstvenih problema, imajući u vidu činjenicu da je uzrok obolevanja i umiranja velikog broja žena &scaron;irom sveta. Oko 85% karcinoma grlića materice dijagnostikuje se u zemljama u razvoju, čineći čak 15% svih malignih tumora kod žena, dok u razvijenim zemljama ovaj procenat iznosi 3,6% novootkrivenih karcinoma. Prema podacima Registra za rak Vojvodine, u AP Vojvodini u 2011. godini, od ukupnog broja novoregistrovanih malignih bolesti kod žena, karcinom grlića materice se nalazio na četvrtom mestu, sa procentualnim uče&scaron;ćem od 6,66%, dok je najveći broj novoobolelih slučajeva u starosnoj grupi 45&ndash;49 godina, pokazujući trend pomeranja prema mladjim starosnim grupama. Primena novih, savremenih dijagnostičkih metoda u inicijalnom zbrinjavanju obolelih od karcinoma grlića materice može doprineti pravilnijem tretmanu bolesti, utičući na tok bolesti, ishod i preživljavanje. PET/CT je hibridna imidžing metoda koja poslednjih godina zauzima značajno<br />mesto u određivanju stadijuma malignih bolesti i dijagnostikovanju recidiva, a kojom se stiče uvid u metaboličko/funkcionalni status ispitivanih tkiva i organa, superponiran na morfoanatomsku CT sliku. Kako je za cilj istraživanja postavljeno utvrđivanje značaja PET/CT pregleda u preoperativnoj evaluaciji karcinoma grlića materice, ispitanice koje su ispunjavale kriterijume za uključivanje u istraživanje su operisane nakon načinjenog PET/CT pregleda, a zatim su poređeni parametri dobijeni kliničkim pregledom, PET/CT pregledom, intraoperativnim pregledom i patohistolo&scaron;kim pregledom. Rezultati načinjenog istraživanja ukazuju da hibridni PET/CT imidžing ne demonstrira prednost u odnosu na dosada&scaron;nje preporuke vezane za preoperativnu dijagnostičku evaluciju ispitanica sa ranim stadijumom karcinoma grlića materice, naročito u detekciji postojanja primarnog tumora dimenzija manjih od 7mm i u detekciji prisustva mikrometastaza u lokoregionalnim limfnim čvorovima zbog jo&scaron; uvek ograničene prostorne rezolucije. PET/CT je pokazao izuzetno visoku specifičnost u utvrđivanju nepostojanja primarnog tumora i visoku komplementarnost sa patohistolo&scaron;kim nalazom. Uočeno je da PET/CT demonstrira statistički značajniju tačnost u proceni stepena pro&scaron;irenosti osnovne bolesti u odnosu na kliničko i intraoperativno utvrđivanje stepena pro&scaron;irenosti osnovne bolesti. Standardizovana vrednost preuzimanja radiofarmaka (SUV) zavisna od histolo&scaron;kog tipa karcinoma grlića materice, demonstrirajući najvi&scaron;e vrednosti u planocelularnom karcinomu i u lo&scaron;e diferentovanom tip G3 karcinomu grlića materice, pozitivno korelirajući sa promerom tumora. Pokazujući značajan potencijal u detekciji primarnog karcinoma grlića materice, kao i u detekciji metastaza u lokoregionalnim limfnim čvorovima, PET/CT nalazi svoje mesto u dijagnostičkoj obradi bolesnica sa karcinomom grlića materice.</p> / <p>Despite the existence of the diagnostic procedures for early diagnosis, implementing preventive screening programs and long preinvasive period in which it is possible to perform detection, cervical cancer remains one of the leading health problems, bearing in mind the fact that it is the cause of morbidity and mortality of a large number of women throughout the world. About 85% cases of cervical cancer are diagnosed in underdeveloped and developing countries. In economically underdeveloped countries, cervical cancer accounts for 15% of all malignant tumors in women, whereas in developed countries it is 3.6% of new cancers. According to data from the Cancer Registry of Vojvodina, in AP Vojvodina, in 2011, of the total number of newly registered malignant diseases in women, cervical cancer was in fourth place, with a percentage share of 6.66% , the largest number of new cases is in the 45-49 years age group, with the shifting the peak in the incidence of cervical cancer towards younger age groups. Applying of new diagnostic methods in the initial management of patients with cervical cancer, indirectly affect the course of the disease, its treatment, and survival. PET-CT hybrid imaging method in recent years occupies an important place in the staging of malignant disease and the diagnosis of recurrence, showing the functional state of certain tissues and organs (PET) with anatomical details (CT). As the aim of this study was to assess the importance of PET / CT scans in the preoperative evaluation of cervical cancer, the women who met the criteria were included in the study, and were operated after having PET / CT scans done, after which the parameters of the results of clinical examination, PET / CT examination, intraoperative examination and histopathological examination, were compared. It was observed that the hybrid PET / CT imaging does not demonstrate the advantage compared to the previous recommendations related to the preoperative diagnostic evaluation of patients with early-stage cervical cancer, especially in the detection of primary tumor measuring less than 7mm and the detection of the presence of micrometastases in the locoregional lymph nodes, due to the still limited spatial resolution. PET / CT showed extremely high specificity in determining the absence of primary tumor and high complementarity with histopathological findings. The study showed that PET / CT demonstrates statistically more significant accuracy in the assessment of the extent of the underlying disease, compared with the clinical and intraoperative determination of the extent of the underlying disease. It has been shown that the standardized uptake value of radiopharmaceuticals (SUV) depends on the histological type of cervical cancer, demonstrating the highest values in squamous-cell carcinoma and then in poorly differentiated G3 carcinoma of the cervix, positively correlating with the diameter of the tumor. Demonstrating significant potential in the detection of primary cervical cancer, as well as in the detection of metastases in locoregional lymph nodes, PET / CT has its place in diagnostic treatment of patients with cervical cancer.</p>

Introduction: The number of breast reconstructions after breast cancer is increasing over the years. This study evaluates complications in the first 30 days after breast reconstruction post mastectomy in different surgical techniques for patients with non-metastatic breast cancer. Methods: Retrospective cohort including patients who underwent breast reconstruction post mastectomy at the National Institute of Neoplastic Diseases (INEN) 2014-2018. Outcomes were immediate complications (first 30 days after surgery). Cumulative incidences were obtained. Association with clinical and demographic factors was evaluated using adjusted relative risk (aRR) obtained via Poisson Regression with robust variances. Results: 2092 patients had mastectomy at INEN during the study period, but only 271 underwent breast reconstruction. From them, 148 had complete data and fulfilled the selection criteria. Median age was 45 years old, 62.16% had overweight/obesity, and 35.85% had clinical stage III. 28.38% had immediate autologous reconstruction, 33.11% immediate prosthetic reconstruction, and 38.51% delayed reconstruction of any type. 48.65% had some surgical complication in the first 30 days, being the most frequent dehiscence (20.27%) and superficial infection (18.92%). Overweight/Obesity (aRR 1.96; 1.24-3.10) and having immediate reconstruction (aRR 1.54; 1.04-2.27) were associated to complications. Prosthetic technique use was protective (aRR 0.59; 0.40-0.85), as well as Neoadjuvant Chemotherapy (aRR 0.65; 0.42-0.99). Conclusions: The prosthetic surgical technique had less early complication incidence than the autologous one. On the other hand, immediate surgery after mastectomy was more likely to present complications compared with delaying. Variables as obesity, neoadjuvant therapy and ECOG intervened in the incidence of complications. / Introducción: El número de reconstrucciones mamarias post cáncer de mama ha ido en aumento. Este estudio evalúa las complicaciones en los primeros 30 días luego de reconstrucción mamaria post mastectomía para cáncer de mama no metastásico en sus diferentes técnicas quirúrgicas. Métodos: Cohorte retrospectiva de pacientes con reconstrucción mamaria post mastectomía en el Instituto Nacional de Enfermedades Neoplásicas (INEN) entre 2014-2018. Los desenlaces fueron las complicaciones quirúrgicas en los 30 días siguientes a la cirugía. Se obtuvieron incidencias acumuladas, y se evaluó su asociación con diversos factores clínico-demográficos mediante riesgos relativos crudos y ajustados (aRR) obtenidos vía Regresión de Poisson con varianza robusta. Resultados: De 2092 pacientes que tuvieron mastectomía en el INEN entre 2014-2018, solo 271 tuvieron reconstrucción mamaria. De ellas 148 tuvieron datos completos y cumplieron los criterios de selección. La mediana de edad fue 45 años, 62.16% tuvieron sobrepeso/obesidad, y 35.85% tenían estadio clínico III. El 28.38% tuvieron reconstrucción inmediata autóloga, 33.11% reconstrucción inmediata usando prótesis, y 38.51% reconstrucción tardía. El 48.65% de los pacientes experimentó alguna complicación en el mes siguiente post cirugía, siendo las complicaciones más frecuentes dehiscencia de sutura (20.27%) e infección superficial (18.92%). Obesidad (RR 1.96; 1.24-3.10), y tener Técnica Inmediata (RR 1.54; 1.04-2.27) se asociaron a más complicaciones. Uso de Técnica Protésica fue protector (RR 0.59; 0.40-0.85), así como también Quimioterapia Neoadyuvante (RR 0.65; 0.42-0.99). Conclusiones: La técnica quirúrgica protésica tuvo menos probabilidades de presentar complicaciones que la autóloga. Asimismo, la cirugía inmediata presenta más probabilidades de presentar complicaciones que la diferida. Las variables como obesidad, terapia neoadyuvante y ECOG intervienen en la presentación de complicaciones. / Tesis

Tumor recurrence after chemotherapy is a major cause of patient morbidity and mortality. Recurrences are thought to be due to small subsets of stem-like cancer cells that are able to survive chemotherapy and drive tumor re-growth. A more complete understanding of stem-like cancer cell regulation is required to develop therapies to better target and eliminate these cells. Slow-cycling stem cells are integral components of adult epithelial tissues and may give rise to cancer stem cell populations that share similar characteristics. These slow-cycling adult stem cells are inherently resistant to traditional forms of chemotherapy and transference of this characteristic may help to explain therapy resistance in cancer stem cell populations. Using a novel application for the proliferation marker CFSE, we have identified populations of slow-cycling cancer cells with tumor initiating capabilities. As predicted, slow-cycling cancer cells exhibit a multi-fold increase in chemotherapy resistance and retain the ability to re-enter the cell cycle. Furthermore, we observed consistent over-expression of the CDK5 activator, p35, in slow-cycling cancer cells. Manipulation of p35 expression in cancer cells affects cell cycle distribution and survival when these cells are treated with traditional forms of chemotherapy. Additionally, we demonstrate that alterations in p35 expression affect BCL2 levels, suggesting a mechanism for the survival phenotype. Combined, our data suggest a model whereby slow-cycling stem-like cancer cells utilize the p35/CDK5 complex to slow cell cycling speed and promote resistance to chemotherapy. Future p35 targeting, in combination with traditional forms of chemotherapy, may help eliminate these cells and reduce tumor recurrence rates, increasing long-term patient survival.

The 21st century brought about a dramatic increase in knowledge about genetic and molecular profiles of cancer. This information has validated the complexity of tumor cells and increased awareness of “nodal proteins”, but has yet to advance the development of rational targeted cancer therapeutics. Nodal proteins are critical cellular proteins that collect biological inputs and distribute the information across diverse biological processes. Survivin acts as a nodal protein by interfacing the multiple signals involved in mitosis and apoptosis and functionally integrate proliferation, cell death, and cellular homeostasis. By characterizing survivin as a target of both Type 1 Insulin-like Growth Factor (IGF-1) and Notch developmental signaling, we contribute to the paradigm of survivin as a nodal protein. The two signaling systems, Notch and IGF-1, regulate survivin by two independent mechanisms. Notch activation induces survivin transcription preferentially in basal breast cancer, a breast cancer subtype with poor prognosis and lack of molecular therapies. Activated Notch binds the transcription factor RBP-Jк and drives transcription from the survivin promoter. Notch mediated survivin expression increases cell cycle kinetics promoting tumor proliferation. Inhibition of Notch in a breast xenograft model reduced tumor growth and systemic metastasis. On the other hand, IGF-1 signaling drives survivin protein translation in prostate cancer cells. Binding of IGF-1 to its receptor activates downstream kinases, mammalian target of rapamycin (mTOR) and p70 S6 protein kinase (p70S6K), which modulates survivin mRNA translation to increase the apoptotic threshold. The multiple roles of survivin in tumorigenesis implicate survivin as a rational target for the “next generation” of cancer therapeutics.

The development and survival of multicellular organisms depends upon the ability of cells to move. Embryogenesis, immune surveillance, wound healing, and metastatic disease are all processes that necessitate effective cellular locomotion. Central to the process of cell motility is the family of integrins, transmembrane cell surface receptors that mediate stable adhesions between cells and their extracellular environment. Many human diseases are associated with aberrant integrin function. Carcinoma cells in particular can hijack integrins, harnessing their mechanical and signaling potential to propagate cell invasion and metastatic disease, one example being integrin α6β4. This integrin, often referred to simply as β4, is defined as an adhesion receptor for the laminin family of extracellular matrix proteins. The role of integrin β4 in potentiating carcinoma invasion is well established, during which it serves both a mechanical and signaling function. miRNAs are short non-coding RNAs that regulate gene expression posttranscriptionally, and data describing the role of extracellular stimuli in governing their expression patterns are sparse. This observation coupled to the increasingly significant role of miRNAs in tumorigenesis prompted us to examine their function as downstream effectors of β4, an integrin closely linked to aggressive disease in breast carcinoma. The work presented in this dissertation documents the first example that integrin expression correlates with specific miRNA patterns. Moreover, integrin β4 status in vitro and in vivo is associated with decreased expression of distinct miRNA families in breast cancer, namely miR-25/32/92abc/363/363-3p/367 and miR-99ab/100, with purported roles in cell motility. Another miRNA, miR-29a, is significantly downregulated in response to de novo expression of β4 in a breast carcinoma cell line, and β4-mediated repression of the miRNA is required for invasion. Another major conclusion of this study is that β4 integrin expression and ligation can regulate the expression of SPARC in breast carcinoma cells. These data reveal distinct mechanisms by which β4 promotes SPARC expression, involving both a miR-29a-mediated process and a TOR-dependent translational mechanism. Our observations establish a link between miRNA expression patterns and cell motility downstream of β4 in the context of breast cancer, and uncover a novel effector of β4-mediated invasion.

<p>Karcinom bronha je danas u svetu najče&scaron;ći uzrok smrti povezanih sa malignim bolestima. U XX veku je registrovan značajan porast kako incidence, tako i mortaliteta karcinoma bronha u većini zemalja. Medijana&nbsp; preživljavanja u svim stadijumima bolesti se značajno pobolj&scaron;ala poslednjih godina XX veka, ali nedovoljno u odnosu na očekivano. U najvećem broju slučajeva, bolest se otkriva u uznapredovalom stadijumu, kada je radikalno hirur&scaron;ko lečenje kao optimalan vid lečenja nemoguće. Određivanje stadijuma bolesti (stejdžing) je najbitniji segment u evaluaciji svakog bolesnika s karcinomom bronha. Utvrđivanje zahvaćenosti medijastinalnih&nbsp; limfnih čvorova karcinomom je od posebne važnosti, jer je u velikom broju slučajeva upravo nodalni status faktor koji određuje svsishodnost primene hirur&scaron;kog lečenja, radioterapije i hemioterapije, a samim tim i jedan od bitnih faktora prognoze bolesnika sa nemikrocelularnim karcinomom bronha NSCLC. Bolesnici sa dokazanom zahvaćeno&scaron;ću N2 medijastinalnih limfnih čvorova se svrstavaju u IIIA stadijum NSCLC koji je potencijalno resektabilan, dok se bolesnici sa dokazanom zahvaćeno&scaron;ću N3 medijastinalnih limfnih čvorova svrstavaju u IIIB stadijum NSCLC, koji se smatra neresektabilnim. Cilj ove doktorske disertacije je bio da se utvrdi da li postoje prognostički značajni faktori za rezultat lečenja medijastinoskopski dokazanog N2 i N3 stadijuma NSCLC. Studija je bila nerandomizovana, delom retrospektivnog, a delom prospektivnog karaktera. U ispitivanje je uključeno 60 bolesnika lečenih u Institutu za plućne bolesti Vojvodine tokom&nbsp; 2006., 2007. i 2008. godine. Kod svih uključenih bolesnika medijastinoskopijom je dokazana propagacija NSCLC u medijastinalne limfne čvorove. U radu su analizirani sledeći faktori: pol, starost, ECOG performans status, pridružena hronična opstruktivna bolest pluća (HOBP), pridruženo kardiovaskularno oboljenje sa simtomatologijom klasifikovanom prema NYHA, T faktor, lokalizacija i broj medijastinoskopski dokazanih metastatski zahvaćenih limfnih čvorova, vrsta primenjenog&nbsp; lečenja (hemioradioterapija, hemioterapija, operacija), rezultat lečenja (odgovor na terapiju i preživljavanje). Univarijantnom analizom je utvrđeno da su kod bolesnika sa medijastinoskopski dokazanim N2 i N3 stadijumom NSCLC prognostički faktori koji su imali uticaj na lo&scaron;ije preživljavanje bili: ECOG PS 2 (p=0,00000), pridruženo kardivaskularno oboljenja sa simptomatologijom klase NYHA II (p=0,00113), zahvaćenost kontralateralnih medijastinalnih medijastinalnih limfnih čvorova (N3 stadijum) (p=0,000003), dok je uticaj zahvaćenosti vi&scaron;e pozicija ipsilateralnih medijastinalnih limfnih čvorova (multi station N2) bio na granici statističke značajnosti (p=0,05385). Utvrđeno je da bolesnici sa N2 i N3 stadijumom NSCLC lečeni hemioradioterapijom imaju bolju stopu odgovora na primenjenu terapiju u odnosu na bolesnike lečene samo hemioterapijom (p=0,03118), kao i da operativno lečenje primenjeno kod bolesnika koji su imali dobar odgovor na sprovedenu terapiju ima statistički značajan uticaj u vidu boljeg preživljavanja (p=0,00121). Univarijantnom analizom nije utvrđen značajan uticaj sledećih faktora na preživljavanje bolesnika sa N2 i N3 stadijomom NSCLC: pol, starost, pridružena HOBP, skvamozni tip NSCLC i T faktor. Multivarijantnom analizom su kao nezavisni prognostički faktori na preživljavanje bolesnika sa N2 i N3 stadijumom NSCLC utvrđeni klinički N status (bolje preživljavanje ima N2 u odnosu na N3 stadijum) i sprovedena terapija (bolje preživljavanje ima hemioradioterapija u odnosu na hemioterapiju). Dobijeni rezultati navode nas na zaključak da su pozicija i broj zahvaćenih pozicija medijastinalnih limfnih čvorova, koji su utvrđeni medijastinoskopski, kao i sprovođenje multimodalnog lečenja ključni prognostički faktori za preživljavanje bolesnika sa N2 i N3 stadijumom NSCLC.</p> / <p>Lung&nbsp; cancer&nbsp; is&nbsp; the&nbsp; most&nbsp; common cause of cancer&nbsp; related mortality&nbsp; worldwide.&nbsp; Increase&nbsp; in&nbsp; both&nbsp; incidence&nbsp; and mortality&nbsp; of&nbsp; lung&nbsp; cancer&nbsp; was&nbsp; registered&nbsp; throughout&nbsp; 20th century. The median survival in every stage of lung cancer has been improved in last years of 20th century but it is still not satisfactory. In most cases, lung cancer is diagnosed in advanced&nbsp; stage&nbsp; when&nbsp; surgical&nbsp; treatment&nbsp; as&nbsp; the&nbsp; optimal approach&nbsp; is&nbsp; not&nbsp; possible. Staging&nbsp; is&nbsp; the&nbsp; most&nbsp; important element&nbsp; in&nbsp; the&nbsp; evaluation&nbsp; of&nbsp; every&nbsp; lung&nbsp; cancer&nbsp; patient. Mediastinal lymph node involvement is crucial, because in most of the cases nodal staging is factor which determines appropriate use of surgery, radiotherapy and chemotherapy and it is one of the important factors influencing prognosis of lung cancer patients. Patients with proven involvement of ipsilateral&nbsp; mediastinal&nbsp; lymph&nbsp; nodes&nbsp; (N2&nbsp; stage)&nbsp; are categorized&nbsp; in&nbsp; IIIA&nbsp; stage&nbsp; which&nbsp; is&nbsp; considered&nbsp; to&nbsp; be potentially resectable, and patients with proven involvement of&nbsp; contralateral&nbsp; mediastinal&nbsp; lymph&nbsp; nodes&nbsp; (N3&nbsp; stage)&nbsp; are categorized&nbsp; in&nbsp; IIIB&nbsp; stage,&nbsp; which&nbsp; is&nbsp; considered&nbsp; to&nbsp; be nonresectable. The aim of this study was the determination of&nbsp; significant&nbsp; prognostic&nbsp; factors&nbsp; that&nbsp; have&nbsp; influence&nbsp; on treatment&nbsp; and&nbsp; survival&nbsp; of&nbsp; non-small&nbsp; cell&nbsp; lung&nbsp; cancer (NSCLC)&nbsp; patients&nbsp; in&nbsp; stage&nbsp; N2&nbsp; and&nbsp; N3.&nbsp; Study&nbsp; was nonrandomized,&nbsp;&nbsp; partially&nbsp;&nbsp; retrospective&nbsp;&nbsp; and&nbsp;&nbsp; partially prospective. It included 60 patients treated at the Institute for Pulmonary&nbsp; Diseases&nbsp; of&nbsp; Vojvodina&nbsp; during&nbsp; 2006,&nbsp; 2007&nbsp; and 2008. Cancer involvement of mediastinal lymph nodes was determined by mediastinoscopy in every patient. In study we analyzed following factors: gender, age, ECOG performance&nbsp;&nbsp; status,&nbsp;&nbsp; associated&nbsp;&nbsp; chronic&nbsp;&nbsp; obstructive pulmonary&nbsp; disease&nbsp; (COPD),&nbsp; associated&nbsp; cardiovascular disease with symptoms graded by NYHA classification, T status, position and number of involved mediastinal lymph nodes,&nbsp; applied&nbsp; treatment&nbsp; (surgery,&nbsp; chemoradiotherapy, chemotherapy alone), treatment result (response to treatment and&nbsp; survival).&nbsp; Prognostic&nbsp; factors&nbsp; for&nbsp; poorer&nbsp; survival&nbsp; on univariant analysis were ECOG PS 2 (p=0,0000), associated cardiovascular&nbsp;&nbsp; disease&nbsp;&nbsp; with&nbsp;&nbsp; symptoms&nbsp;&nbsp; NYHA&nbsp;&nbsp; II (p=0,00113)&nbsp; and&nbsp; involvement of&nbsp; contralateral&nbsp; mediastinal lymph nodes (N3 stage) (p=0,00003) while multi station N2 disease was borderline significant at level of p=0,05385. It was determined that patients treated with chemoradiotherapy achieved better response to treatment compared to patients treated&nbsp; with&nbsp; chemotherapy&nbsp; alone&nbsp; (p=0,03118).&nbsp; Univariant analyses&nbsp; did&nbsp; not&nbsp; confirm&nbsp; significance&nbsp; of&nbsp; gender,&nbsp; age, associate COPD, squamous cell lung cancer and T factor on survival. Multivariante&nbsp; analyses&nbsp; identified&nbsp; N&nbsp; status&nbsp; (better survival has N2 stage compared to N3 stage of NSCLC) and conducted treatment (better survival has&nbsp; chemoradiotherapy compared to chemotherapy alone) as independent prognostic factors.&nbsp; Our&nbsp; results&nbsp; suggest&nbsp; that&nbsp; position&nbsp; and&nbsp; number&nbsp; of cancer involved&nbsp; mediastinal lymph nodes position,&nbsp; proven by mediastinoscopy, as well as the conducted multimodality treatment are key prognostic factors which might influence the survival of patients with N2 and N3 stage of NSCLC.</p>

Concept cancer transition in the context of selected theoretical approaches related to the process of morbidity and mortality in recent decades: Case study for Czechia Abstract The aim of the diploma thesis is to introduce the cancer transition concept and to contextualize it in relation to other theoretical concepts that concentrate on change in the structure of mortality by causes of death. Furthermore, in the context of cancer transition, the current state of mortality of neoplasms is illustrated reflecting its connection to infection in the population of Czechia, and its development is covered over the 1994-2018 period. The concept of cancer transition is based on the idea that as the society develops, the proportion of deaths by infection-related neoplasms decreases and the proportion of deaths caused by non-infection-related neoplasms increases. The concept thus essentially follows Omran's theory of the epidemiological transition. However, the concept of cancer transition has, so far, been theoretically used only to a relatively limited extend in literature and has usually been described rather indirectly. In this work, it is presented as a separate theoretical concept dealing with the change in the structure of mortality in terms of causes of death and its connection to existing concepts related to...

This diploma thesis deals with the urban-architectural study of a new residential location on the place of the former area of the artistic-industrial enterprises in Bučovice. It is a brownfields near the Bučovice castle in the historic central zone of the town. The proposal focuses on the urban-architectural solution of the whole area including the conceptual consideration which responds to the possibilities and limits of the development of the industrial complex with a focus on the new building and architectural neoplasm in the historical surroundings.

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The thesis evaluates the results of experimental protocol involving the fertility sparing treatment procedure in early stage cervical carcinoma (LAP I protocol). Sentinel lymph node detection and experimental extirpation of afferent channels using laparoscopy and its technical aspects were analysed in prospective group of 85 women. The oncologic results and early/late morbidity show that established surgical procedures can be considered safe with minimal morbidity, provided that the indication criteria are met. The second part analyses the results of 148 women with no further pregnancy plans suffering from cervical tumors less than 2 cm in size with invasion less than half of the stroma (LAP II protocol). The oncological results in our defined group are very good and comparable to 'standard' procedure of modified radical hysterectomy type B or C with lower morbidity. In the separate section the thesis analyses the possibilities of laparoscopy in endometrial cancer treatment including the potentials of use of sentinel lymph node detection and technical aspects of laparoscopy in obese women. Currently the biggest controversy is the use of laparoscopy in malignant ovarian tumors. Our oncogynaecological study group at FN Motol prefers the laparotomic approach and we chose to include the set of advanced...