Browsing by Author "Simtniece, Zane"

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    The first evidence of hereditary and familial gastric cancer in Latvia : Implications for prevention
    (2012) Vanags, Andrejs; Štrumfa, Ilze; Gardovskis, Andris; Aboliņs, Arnis; Simtniece, Zane; Trofimovičs, Genadijs; Gardovskis, Janis; Department of Surgery; Department of Pathology
    Background and Objective: Gastric cancer is a frequent cause of cancer mortality. The prognosis of established tumor is unfavorable due to the propensity to spread and limited treatment efficiency. Therefore, prevention has a high significance. We tested a population screening approach in order to identify families with an increased gastric cancer load for further surveillance. Material and Methods: Population screening was performed by questionnaire reaching 76.6% of the population. Hereditary gastric cancer (HGC) syndrome was diagnosed if 3 mutually first-degree relatives with gastric cancer were reported in the kindred. Additional group (HGC2) of families with 2 first-degree relatives affected by gastric cancer was identified. Results: The HGC syndrome was diagnosed in 0.11%, but HGC2 syndrome, in 0.4% probands. The gastric cancer frequency among blood relatives was 25.2% (95% CI, 20.6%-30.4%) in HGC, but 16.0% (95% CI, 13.8%-18.5%) in HGC2 families. The mean age at diagnosis of cancer was 56.9 years (95% CI, 53.4-60.3) in HGC and 62.5 years (95% CI, 60.1-64.8) in HGC2. The mean survival was 2.6 years (95% CI, 1.2-4.0). Conclusions: Population screening identifies reasonable number of families with a high frequency of gastric cancer. The frequency of gastric cancer and an unfavorable course characterized by low survival justify surveillance in families with 2 or 3 first-degree relatives affected by gastric cancer. Population screening provides the age characteristics of the respective tumors in order to adjust the surveillance schedule.
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    Morphological and immunohistochemical profile of pancreatic neuroendocrine neoplasms
    (2015-07-30) Simtniece, Zane; Vanags, Andrejs; Strumfa, Ilze; Sperga, Maris; Vasko, Ervins; Prieditis, Peteris; Trapencieris, Peteris; Gardovskis, Janis; Department of Pathology; Department of Surgery; Department of Radiology
    The study represents a comprehensive retrospective morphological and immunohistochemical profiling of pancreatic neuroendocrine neoplasms (PNENs) in order to reveal the associations between morphological and molecular parameters. The local tumour spread (T), presence of metastases in regional lymph nodes (N) and distant organs (M), tumour grade (G) and resection line status (R) by pathology findings (pTNMGR), mitotic activity, perineural, vascular and lymphatic invasion were assessed in 16 surgically resected PNENs. By immunohistochemistry, expression of Ki-67, p53, p27, p21, cyclin D1, Bcl-2, E-cadherin, CD44, vimentin, cyclooxygenase 2 (COX-2), microvascular density, and cytokeratin (CK) spectrum, along with neuroendocrine, intestinal and squamous markers were detected. Descriptive statistics, Chi-square test, Spearman’s rank correlation, Mann–Whitney and Kruskal–Wallis methods were applied; p < 0.05 was considered significant. Ki-67, CK19, p63, vimentin and COX-2 were significantly up-regulated in PNENs in comparison to benign pancreatic islets. A complex network of morphological and molecular associations was identified. Ki-67 correlated with PNEN size (p = 0.022), the World Health Organization 2004 and 2010 classification grades (p = 0.021 and p = 0.002), stage (p = 0.028) and mitotic count (p = 0.007) but among molecular markers – with CK19 (p = 0.033) and vimentin (p = 0.045). CK19 was significantly up-regulated in PNENs, having higher pT (p = 0.018), pR (p = 0.025), vascular (p = 0.020), perineural (p = 0.026) and lymphatic invasion (p = 0.043). In conclusion, proliferation activity (by Ki-67), E-cadherin, vimentin and CK19 are important molecular characteristics of PNENs due to significant associations with morphological tumour characteristics, pTNMGR and invasive growth.
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    Operēta aizkuņģa dziedzera vēža prognostiskie faktori. Promocijas darba kopsavilkums
    (Rīgas Stradiņa universitāte, 2015) Simtniece, Zane; Gardovskis, Jānis; Štrumfa, Ilze
    Pēc Veselības Ekonomikas centra datiem, saslimstība ar aizkuņģa dziedzera vēzi pieaug: 2007. gadā atklāti 360, bet 2010. gadā – 405 gadījumi. Analogu incidences pieaugumu novēro arī citviet pasaulē. Aizkuņģa dziedzera vēža 5 gadu izdzīvotība, pacientam saņemot labāko iespējamo ārstēšanu, t.sk. radikālu ķirurģisku terapiju, ir 15%, bet kopējā aizkuņģa dziedzera vēža grupā 5 gadu izdzīvotība ir tikai 5%, pie tam rezultāti nav būtiski uzlabojušies 30 gadu laikā. Līdz ar to ir būtiski pētīt aizkuņģa dziedzera audzēju bioloģisko potenciālu un to noteicošos mehānismus, lai varētu rast mērķa molekulas iespējamai terapijai un precizēt katra pacienta individuālo prognozi. Pētījuma mērķis ir noteikt potenciāli radikāli operētu aizkuņģa dziedzera duktālu adenokarcinomu (ADDA) un aizkuņģa dziedzera endokrīnu audzēju (AEA) morfoloģisko un imūnhistoķīmisko profilu un šo pacientu prognozi. Materiāli un metodes. Pētījums ir retrospektīvs, uz pierādījumiem balstīts potenciāli radikāli operētu ADDA un AEA morfoloģisks un imūnhistoķīmisks izvērtējums, nosakot 14 morfoloģiskus un 21 imūnhistoķīmiskus parametrus un iekļaujot izdzīvotības analīzi. Datu statistiskai apstrādei tika izmantota aprakstošā un analītiskā metode. Pētījums ir veikts saskaņā ar Helsinku deklarāciju un Rīgas Stradiņa universitātes ētikas komitejas atļauju. Rezultāti. Pētījumā iekļauti 78 potenciāli radikāli operētu ADDA pacientu un 16 AEA pacientu gadījumi. ADDA pacientu vidējais vecums bija 63,4 gadi, AEA pacientiem – 59,4 gadi. ADDA raksturīgas šādas pazīmes: liels audzēja izmērs (vidējais izmērs 3,6 cm), biežs pT3 – 98,7%, pN1 – 67,5%, vidēja vai zema diferenciācijas pakāpe – 46,2% un 35,9% gadījumos attiecīgi, perineirāla invāzija – 87,2% un R1 – 57,5% gadījumos. AEA raksturīgas mazāk agresīvas pazīmes: pT3 – 37,5%, pN1 – 20,0%, R1 – 27,3% gadījumu; visbiežāk tie bija labi diferencēti endokrīni audzēji ar neskaidru potenciālu (56,3%). Salīdzinot neoplastiskās šūnas ar atbilstošiem labdabīgiem audiem, konstatēta CK 20, CK 5/6 un COX-2 jauna ekspresija ADDA gadījumos, bet AEA gadījumos – CK 7, CK 19, p63, vimentīna un COX-2 ekspresija. ADDA audos pastiprinās Ki-67, p53, p21, ciklīna D1, hromogranīna A un vimentīna ekspresija (salīdzinot vidējo pozitīvo šūnu relatīvos daudzumus), bet AEA – Ki-67 un CD44. Savukārt ADDA šūnās samazinās p27, CK 7, CK 19 un CD56 ekspresija. Mediānais izdzīvotības laiks pēc potenciāli radikālas operācijas bija 11,0 mēneši ADDA pacientiem, bet starp AEA pacientiem 2/ 14 pacienti nomira 1 un 15 mēnešus pēc operācijas. Prognostiska nozīme bija audzēja invāzijai lielajos asinsvados (p = 0,013), nekrozei (p = 0,001), paaugstinātai vimentīna (p = 0,002) un CD44 (p = 0,018) ekspresijai, kā arī p27 izzudumam (p = 0,003) ADDA gadījumos. Secinājumi. Potenciāli radikāli operētu aizkuņga dziedzera duktālas adeno-carcinomas pacientu mediānais izdzīvotības laiks ir īss. Diagnostikas brīdī audzējam bieži ir liels izmērs. Šiem audzējiem raksturīga izteikta invazivitāte un izplatība ārpus aizkuņģa dziedzera audiem. Pēc imūnhistoķīmiskā izvērtējuma, prognostiska nozīme ir epiteliāli-mezenhimālai transformācijai, paaugstinātai CD44 ekspresijai un p27 zudumam. Aizkuņģa dziedzera endokrīni audzēji ir mazāk agresīvi, bet uz agresīvu audzēja progresiju un izplatību norāda samazināta E-kadherīna ekspresija, kā arī iegūta CK 19 un vimentīna ekspresija.
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    Prognostic Factors of Surgically Treated Pancreatic Cancer. Doctoral Thesis
    (Rīga Stradiņš University, 2015) Simtniece, Zane; Gardovskis, Jānis; Štrumfa, Ilze
    According to data provided by the Centre of Health Economics of Latvia, the incidence of pancreatic tumours is increasing: there were 360 diagnosed cases in 2007 but 405 cases in 2010. Similar growth of incidence has been observed worldwide. The 5-year survival of pancreatic cancer is 15% for patients receiving the best possible treatment, including radical surgical treatment, but in the total group of pancreatic cancer, the 5-year survival rate is only 5%. In addition, the treatment results have not improved significantly over last 30 years. Therefore, it is essential to study the biological potential and its underlying mechanisms of pancreatic cancer in order to define possible treatment target molecules and to specify individual prognosis of each patient. The aim of the research work is to detect the morphological and immune-histochemical profile of potentially radically operated pancreatic ductal adenocarcinoma (PDAC) and pancreatic endocrine tumours (PETs) and the clinical and prognostic importance of it in local patients. Materials and methods. This study was performed as a retrospective, evidence-based morphological and immunohistochemical investigation of potentially radically operated PDACs and PETs, including 14 morphological and 21 immunohistochemical parameters and survival analysis by applying a wide scope of descriptive and analytic statistic methods. The research was carried out in accordance with the Declaration of Helsinki and received approval from the Committee of Ethics of Riga Stradins University. Results. In the study, 78 cases of potentially radically operated PDAC and 16 cases of PET were selected. The mean age was 63.4 years for PDAC and 59.4 years for PET patients. PDAC had the following characteristics: large tumour size (mean size 3.6 cm), frequent pT3 – 98.7%, pN1 – 67.5%, moderate or poor differentiation in 46.2% and 35.9% of cases, perineural invasion – 87.2% and R1 – 57.5% of cases. PET were characterised by less aggressive characteristics: pT3 – 37.5%, pN1 – 20.0%, R1 – 27.3% of cases; well differentiated endocrine tumours with unclear behaviour predominated (56.3%). Comparing neoplastic cells with the non-neoplastic counterparts, CK 20, CK 5/6, COX-2, Ki-67, p53, p21, cyclin D1, chromogranin A and vimentin were up-regulated in PDAC, but CK 7, CK 19, p63, vimentin, COX-2, Ki-67 and CD44 in PET. In contrast, expression of p27, CK 7, CK 19 and CD56 was lost in PDAC cases. The median overall survival after potentially radical operation was 11.0 months for PDAC patients, but among PET patients 2/ 14 patients died after 1 and 15 months. Tumour invasion in large blood vessels (p = 0.013), necrosis (p = 0.001), increased expression of vimentin (p = 0.002) and CD44 (p = 0.018), decreased expression of p27 (p = 0.003) showed prognostic significance in PDAC cases. Conclusion. The overall survival after potentially radically treated PDAC is poor. At the time of diagnostics, the tumours are already large. PDAC is characterised by high invasiveness and thus able to spread. By immunohistochemical evaluation, the epithelial-mesenchymal transition, increased CD44 expression and loss of p27 had prognostic significance. PET are less aggressive, but decreased E-cadherin expression, up-regulation of CK 19 and vimentin expression can indicate tumour progression and spreading.
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    Prognostic Factors of Surgically Treated Pancreatic Cancer. Summary of the Doctoral Thesis
    (Rīga Stradiņš University, 2015) Simtniece, Zane; Gardovskis, Jānis; Štrumfa, Ilze
    According to data provided by the Centre of Health Economics of Latvia, the incidence of pancreatic tumours is increasing: there were 360 diagnosed cases in 2007 but 405 cases in 2010. Similar growth of incidence has been observed worldwide. The 5-year survival of pancreatic cancer is 15% for patients receiving the best possible treatment, including radical surgical treatment, but in the total group of pancreatic cancer, the 5-year survival rate is only 5%. In addition, the treatment results have not improved significantly over last 30 years. Therefore, it is essential to study the biological potential and its underlying mechanisms of pancreatic cancer in order to define possible treatment target molecules and to specify individual prognosis of each patient. The aim of the research work is to detect the morphological and immune-histochemical profile of potentially radically operated pancreatic ductal adenocarcinoma (PDAC) and pancreatic endocrine tumours (PETs) and the clinical and prognostic importance of it in local patients. Materials and methods. This study was performed as a retrospective, evidence-based morphological and immunohistochemical investigation of potentially radically operated PDACs and PETs, including 14 morphological and 21 immunohistochemical parameters and survival analysis by applying a wide scope of descriptive and analytic statistic methods. The research was carried out in accordance with the Declaration of Helsinki and received approval from the Committee of Ethics of Riga Stradins University. Results. In the study, 78 cases of potentially radically operated PDAC and 16 cases of PET were selected. The mean age was 63.4 years for PDAC and 59.4 years for PET patients. PDAC had the following characteristics: large tumour size (mean size 3.6 cm), frequent pT3 – 98.7%, pN1 – 67.5%, moderate or poor differentiation in 46.2% and 35.9% of cases, perineural invasion – 87.2% and R1 – 57.5% of cases. PET were characterised by less aggressive characteristics: pT3 – 37.5%, pN1 – 20.0%, R1 – 27.3% of cases; well differentiated endocrine tumours with unclear behaviour predominated (56.3%). Comparing neoplastic cells with the non-neoplastic counterparts, CK 20, CK 5/6, COX-2, Ki-67, p53, p21, cyclin D1, chromogranin A and vimentin were up-regulated in PDAC, but CK 7, CK 19, p63, vimentin, COX-2, Ki-67 and CD44 in PET. In contrast, expression of p27, CK 7, CK 19 and CD56 was lost in PDAC cases. The median overall survival after potentially radical operation was 11.0 months for PDAC patients, but among PET patients 2/ 14 patients died after 1 and 15 months. Tumour invasion in large blood vessels (p = 0.013), necrosis (p = 0.001), increased expression of vimentin (p = 0.002) and CD44 (p = 0.018), decreased expression of p27 (p = 0.003) showed prognostic significance in PDAC cases. Conclusion. The overall survival after potentially radically treated PDAC is poor. At the time of diagnostics, the tumours are already large. PDAC is characterised by high invasiveness and thus able to spread. By immunohistochemical evaluation, the epithelial-mesenchymal transition, increased CD44 expression and loss of p27 had prognostic significance. PET are less aggressive, but decreased E-cadherin expression, up-regulation of CK 19 and vimentin expression can indicate tumour progression and spreading.