NOS2 Polymorphism in Aspect of Left and Right-Sided Colorectal Cancer.

Background: The NOS2 gene polymorphism rs2297518 is associated with an increased level of NO, which could contribute to colorectal cancer (CRC) development. We hypothesized that the potential influence of the NOS2 gene polymorphism on cancer development may vary between right-sided and left-sided colon cancers, and rectal cancers. The aim of this study was to determine the rs2297518 polymorphism influence on colorectal cancer development with regard to tumor localization. Methods: This case-control study included 199 patients with CRC and 120 controls. The qPCR endpoint genotyping was conducted using the TaqMan® genotyping assay. Results: This study revealed significant differences in tumor characteristic and in the minor alelle A frequency in the NOS2 genotype between colorectal cancers with different localizations. The mucinous adenocarcinoma was diagnosed significantly more often in right-sided cancers than in left-sided (30.6% vs. 10.9%, p = 0.009) and rectal cancers (30.6% vs. 7.1%, p = 0.0003). The minor allele A of the NOS2 genotype was observed more frequently in right-sided cancers than in left-sided cancers (44.9% vs. 23.1%, p = 0.0137) and more frequently in rectal cancers than in left-sided cancers (40.0% vs. 23.1%, p = 0.0285). Conclusions: In conclusion, the results support the hypothesis that the SNP rs2297518 of the NOS2 gene influences colorectal cancer development with regard to tumor localization.

Association between Glutathione S-Transferases Gene Variants and COVID-19 Severity in Previously Vaccinated and Unvaccinated Polish Patients with Confirmed SARS-CoV-2 Infection.

As the outcome of COVID-19 is associated with oxidative stress, it is highly probable that polymorphisms of genes related to oxidative stress were associated with susceptibility and severity of COVID-19. The aim of the study was to assess the association of glutathione S-transferases (GSTs) gene polymorphisms with COVID-19 severity in previously vaccinated and unvaccinated Polish patients with confirmed SARS-CoV-2 infection. A total of 92 not vaccinated and 84 vaccinated patients hospitalized due to COVID-19 were included. The WHO COVID-19 Clinical Progression Scale was used to assess COVID-19 severity. GSTs genetic polymorphisms were assessed by appropriate PCR methods. Univariable and multivariable analyses were performed, including logistic regression analysis. GSTP1 Ile/Val genotype was found to be associated with a higher risk of developing a severe form of the disease in the population of vaccinated patients with COVID-19 (OR: 2.75; p = 0.0398). No significant association was observed for any of the assessed GST genotypes with COVID-19 disease severity in unvaccinated patients with COVID-19. In this group of patients, BMI > 25 and serum glucose level > 99 mg% statistically significantly increased the odds towards more severe COVID-19. Our results may contribute to further understanding of risk factors of severe COVID-19 and selecting patients in need of strategies focusing on oxidative stress.

Glutathione S-Transferase P1 Genetic Variant's Influence on the HbA1c Level in Type Two Diabetic Patients.

GST (glutathione S-transferases) are capable of influencing glucose homeostasis, probably through regulation of the response to oxidant stress. The aim of our study was to investigate the relationship between GSTP1 gene polymorphism and glycated hemoglobin (HbA1c) levels in type two diabetic (T2D) patients. A total of 307 T2D patients were included. Analysis of the GSTP1 gene polymorphism (rs1695) was conducted using the TaqMan qPCR method endpoint genotyping. HbA1c was determined using a COBAS 6000 autoanalyzer. A univariable linear regression and multivariable linear regression model were used to investigate the association between mean HbA1c level and GSTP1 gene polymorphism, age at T2D diagnosis, T2D duration, therapy with insulin, gender, BMI, smoking status. GSTP1 Val/Val genotype, age at T2D diagnosis, T2D duration and therapy with insulin were statistically significant contributors to HbA1c levels (p < 0.05). Multivariable regression analysis revealed that GSTP1 (Val/Val vs. Ile/Ile) was associated with higher HbA1c even after adjustment for variables that showed a statistically significant relationship with HbA1c in univariable analyses (p = 0.024). The results suggest that GSTP polymorphism may be one of the risk factors for higher HbA1c in T2D patients. Our study is limited by the relatively small sample size, cross-sectional design, and lack of inclusion of other oxidative stress-related genetic variants.

Burden of cancer in Poland analysed using potential years of life lost.

AIM OF THE STUDY: The aim was to assess the impact of the most frequent cancer-related causes of death in Poland by estimating the years of potential life lost (YPLL) and to compare different measures of the burden of cancer deaths on the population. MATERIAL AND METHODS: Mortality rate, YPLL and mean YPLL were calculated for the 11 most frequently recorded cancer-related causes of death in Poland. YPLL were measured applying the up-to-date reference life tables proposed by the Institute for Health Metrics and Evaluation and used in the Global Burden of Disease study (GBD 2015). Absolute numbers of cancer deaths by site, gender and five-year age groups were obtained from the Polish National Cancer Registry (2015). RESULTS: In 2015 the total YPLL amounted to 1,990,457, with 23.6% from lung and bronchial cancer. Mean YPLL was 19.79 years and varied considerably according to tumour site (26.12 [brain] - 14.3 [prostate]). Three tumour sites (brain, ovarian and kidney) are positioned higher according to mean YPLL than according to YPLL percentage and mortality percentage. CONCLUSIONS: Our results draw attention to the impact of cancer on society and individual patients. Addressing research efforts to prevention and/or treatment of major YPLL causes could result in a substantial impact on general life expectancy.

Analysis of the survival of patients receiving systemic treatment for melanoma of the skin: a retrospective population study with patients treated in Poland in 2011-2015.

INTRODUCTION: In Poland, it is uniquely possible to assess real effects of the introduction of new oncological therapies on the overall survival in patients as such therapies are funded by one payer only - the National Health Fund (NHF). Data collected by the NHF make it possible to analyse the survival of all patients who were diagnosed with melanoma. AIM: The paper presents findings of a retrospective analysis of the efficacy of systemic treatment in patients with malignant melanoma of the skin in Poland with regard to the overall survival. MATERIAL AND METHODS: The analysis of the overall survival was performed with the Kaplan-Meier method in the population receiving systemic treatment. Three groups of patients were analysed. Group 1 included all patients who had started systemic treatment between 1 March 2011 and 1 March 2015: 1,258 patients. The median overall survival was 8.4 months. Group 2 included 444 patients who had started systemic treatment between 1 March 2011 and 28 February 2013. The median overall survival was 6.6 months in this group. Group 3 included 814 patients who had started systemic treatment between 1 March 2013 and 1 March 2015 and included 546 patients who were also treated in drug programmes with ipilimumab and vemurafenib (approx. 67%). The median overall survival was 9.4 months. RESULTS: A difference in the overall survival between group 3 and 2 was statistically significant (p < 0.05). CONCLUSIONS: The introduction of vemurafenib and ipilimumab into systemic treatment in Poland using public funds had a significant effect on the prolongation of the overall survival in patients with malignant melanoma of the skin.

Cost-effectiveness of somatostatin analogues in the treatment of acromegaly.

INTRODUCTION: Somatostatin analogues (SSAs) are the largest contributor to the direct medical cost of acromegaly management worldwide. The aim of this review was to identify and report available evidence on the cost-effectiveness of SSAs in the treatment of acromegaly. AREAS COVERED: A literature search on relevant papers published up to April 2018 was performed. A total of 22 eligible studies (10 full-text articles and 12 conference abstracts) conducted in 14 countries were included in the analysis. In majority of studies, modelling technique was the principal research method. EXPERT COMMENTARY: The results of cost-effectiveness analyses: 1) support published recommendations where SSAs are indicated as first-line medical treatment for patients with persistent disease after surgery or who are not eligible for surgery; 2) suggest that preoperative medical therapy with SSAs may be highly cost-effective in acromegalic patients with macroadenoma, in centres without optimal surgical results 3) indicate that in some countries pasireotide and pegvisomant appeared to be cost-effective or even dominant strategies in comparison to first-generation SSAs. The main limitation of economic evaluations was the lack of high-quality studies designed to directly compare various treatment strategies in acromegaly.

LanroNET - A Non-Interventional Prospective Study to Assess the Resource Utilisation and Cost of Lanreotide Autogel 120 mg in the Population of Polish Patients with Symptomatic Neuroendocrine Tumours.

Wstep: Celem badania LanroNET byla ocena wykorzystania zasobów medycznych oraz kosztów objawowego leczenia polskich chorych na nowotwory neuroendokrynne z zastosowaniem lanreotydu autogel 120 mg. Material i metody: LanroNET to wieloosrodkowe, nieinterwencyjne, obserwacyjne, prospektywne badanie przeprowadzone w 12 osrod-kach w Polsce. W badaniu uczestniczyli dorosli chorzy na wydzielajace nowotwory neuroendokrynne leczeni lanreotydem autogel 120 mg od przynajmniej 3 miesiecy przed wlaczeniem do badania. Podczas 24-miesiecznej obserwacji rzeczywistej praktyki klinicznej zbierano dane dotyczace wykorzystania zasobów medycznych oraz przebiegu terapii chorych z wydzielajacymi nowotworami neuroendokrynnymi. WYNIKI: W badaniu uczestniczylo 54 chorych na wydzielajace nowotwory neuroendokrynne. Przecietny czas stosowania lanreotydu wynosil 1,7 roku (zakres 0,0-2,2 lata). Badanie ukonczylo 33 pacjentów, najczestsza przyczyna przedwczesnego zakonczenia leczenia (8/16) byla progresja choroby. Calkowity sredni koszt wykorzystanych zasobów bez kosztów farmakoterapii oszacowano na 26 307 zl/EUR 6.030,35 na pacjenta/rok. W czasie badania sredni odstep miedzy wstrzyknieciami lanreotydu wynosil 31,7 dni (6,7). Pod koniec obserwacji, po 24 miesiacach od follow-up, 7 pacjentów stosowalo 42-dniowe odstepy miedzy dawkami. Sredni rzeczywisty koszt lanreotydu autogel 120 mg wyniósl 4216,30 zl/966,49 EUR na pacjenta/28 dni we wspólnej perspektywie platnika i pacjenta i byl nizszy o 554,16 zl/127,02 EUR niz koszt stosowania standardowych 28-dniowych odstepów miedzy dawkami. WNIOSKI: Badanie LanroNET jest pierwszym w Polsce obserwacyjnym dwuletnim badaniem chorych na czynne hormonalnie nowotwo-ry neuroendokrynne zoladkowo-jelitowo-trzustkowe oceniajacym koszty codziennej praktyki klinicznej i koszty leczenia lanreotydem autogel.

An ecological study of the link between the risk of most frequent types of cancer in Poland and socioeconomic variables.

OBJECTIVES: To assess the link between the risks of most frequent cancer sites in Poland and selected socioeconomic variables that potentially affect health outcomes throughout the life course. METHODS: This is a cross-sectional ecological study. Incidence of lung, breast, and colon cancer by voivodeships in 2014 was calculated based on Polish National Cancer Registry. Socioeconomic variables in individual voivodeships were assessed based on Polish Social Cohesion Survey for 2015. Spearman's rank correlation coefficient was used to test the association of incidence rates and socioeconomic variables. The significance level was set at p < 0.05 (two-tailed tests). RESULTS: Statistically significant negative correlation exists between: (1) friend-/neighbour-based social capital and colon and breast cancer, (2) association-based social capital and lung cancer, (3) high religiousness and lung and breast cancer, and (4) income poverty and breast cancer. Statistically significant positive correlation exists between: (1) social isolation, living conditions poverty, poverty resulting from the lack of budget balance, and lung cancer; (2) low/no involvement in religious activity and lung and breast cancer. CONCLUSIONS: Our findings support public health concerns over the implication of socioeconomic environment for cancer.

Dosage and costs of lanreotide Autogel 120 mg administered as part of routine acromegaly care in Poland - two years of data from Lanro-Study.

INTRODUCTION: To evaluate, over 24 months of prospective follow-up, the dosage and costs of lanreotide AUTOGEL 120 mg (ATG120) administered as part of routine acromegaly care in Poland. MATERIAL AND METHODS: A multicentre, non-interventional, observational prospective study on resource utilisation in Polish acromegalic patients treated with ATG120 at 4-week or extended (> 4 weeks) dosing interval. The study population consisted of adult acromegalic patients treated for at least 3 injections of ATG120. The endpoints were: percentage of patients treated with ATG120 at an extended dosing interval (> 4 weeks), mean time between injections, and the cost of ATG120 during a 24-month prospective observation. Costs were calculated in PLN from the public health-care payer and patient perspective for the year 2014. RESULTS: 143 patients were enrolled in, and 132 completed (70% women, 81% macroadenoma, 75% previous surgery) the analysis. During two years, changes in the treatment pattern were reported in 41 patients: 17% of them had increased injection interval and 10% switched to octreotide LAR and then returned to ATG120. Sixty-three patients (48%) received ATG120 at an extended dosing interval. ATG120 was predominantly administered in an out-patient setting (84%) by a health care professional (97%). CONCLUSIONS: The results demonstrated that extended dosing interval of ATG120 is used in a substantial proportion of patients in routine clinical practice in Poland. Such findings support the potential for ATG120 in reducing treatment burden in the real-world clinical environment.

LanroNET, a non-interventional, prospective study to assess the resource utilization and cost of lanreotide autogel 120 mg in Polish patients with neuroendocrine tumors - results of interim analysis.

AIM OF THE STUDY: To examine characteristics and treatment patterns of symptomatic neuroendocrine tumors (NETs) patients who received lanreotide Autogel 120 mg (ATG120) administered as part of routine clinical practice. MATERIAL AND METHODS: Lanro-NET is a national, multicenter, non-interventional, observational study in the population of adult patients with symptomatic NETs treated with ATG120 for at least three months before inclusion. Data on demographic and clinical characteristics of the population, dosing interval regimen and aspects of administration were collected prospectively during 12 months. Costs were calculated from the perspective of public payer for the year 2014. RESULTS: Fifty-two patients were enrolled in the study. Primary tumors were located predominantly in gastrointestinal tract (51.2%), all tumors were metastatic. The most commonly reported disease symptoms were flushing and diarrhea (55.8% of patients). 86% of patients had undergone surgery, chemotherapy and radioisotope therapy were used in 11.6% and 46.5% of patients, respectively. During the 12-months observation 12 (28%) patients received ATG120 at an extended dosing interval (> 4 weeks), the mean number of days between injections was 31.75 (SD 6.74). The cost of ATG12 was estimated at 4273.17 PLN patient/month. In all patients ATG120 was administered by nurse, 51.6% of injections in out-patient setting, 48.4% - in hospital. CONCLUSIONS: This study presents the current use of ATG120 in the population of Polish NETs patients in a realistic clinical settings. Finding that 28% of patients could be treated with extended dose intervals supports the potential for ATG120 of reducing treatment burden.

Assessment of real-world usage of lanreotide AUTOGEL 120 in Polish acromegalic patients - results from the prospective 12-month phase of Lanro-Study.

AIM OF THE STUDY: To assess resource utilization and costs of treatment with lanreotide AUTOGEL 120 mg (ATG120) administered as part of routine acromegaly care in Poland. MATERIAL AND METHODS: A multicentre, non-interventional, observational study on resource utilization in Polish acromegalic patients treated with ATG120 at 4 weeks or extended (> 4 weeks) dosing interval. The study recruited adult acromegalic patients treated medically for ≥ 1 year including at least 3 injections of ATG120. Data on dosing interval, aspects of administration, and resource utilization were collected prospectively during 12 months. Costs were calculated in PLN from the public health-care payer perspective for the year 2013. RESULTS: 139 patients were included in the analysis. Changes in dosing regimen were reported in 14 (9.4%) patients. Combined treatment was used in 11 (8%) patients. Seventy patients (50%) received ATG120 at an extended dosing interval; the mean number of days between injections was 35.56 (SD 8.4). ATG120 was predominantly administered in an out-patient setting (77%), by health-care professionals (94%). Mean time needed for preparation and administration was 4.33 and 1.58 min, respectively, mean product wastage - 0.13 mg. Patients were predominantly treated in an out-patient setting with 7.06 physician visits/patient/year. The most common control examinations were magnetic resonance imaging of brain and brain stem (1.36/patient/year), ultrasound of the neck (1.35/patient/year), GH (1.69/patient/year), glycaemia (1.12/patient/year), IGF-1 (0.84/patient/year), pituitary-thyroid axis hormone levels assessment (TSH-0.58/patient/year, T4-0.78/patient/year). There were 0.43 hospitalizations/patient/year. For direct medical costs estimated at PLN 50 692/patient/year the main item was the costs of ATG120 (PLN 4103.87/patient/month; 97%). The mean medical cost, excluding pharmacotherapy, was PLN 1445/patient/year (out-patient care - 49%, hospitalization - 23%, diagnostics/laboratory tests - 28%). CONCLUSIONS: These results represent the current use of ATG120 in the population of Polish acromegalic patients in a realistic clinical setting. Findings that 50% of patients could be treated with dose intervals of longer than 28 days support the potential of ATG120 to reduce the treatment burden.