Opioid Treatment in Primary Care: Knowledge and Practical Use of Opioid Therapy.

BACKGROUND: Primary care physicians play a key role in initiating opioid therapy. However, knowledge gaps in opioid use and pain management are significant barriers to providing optimal care. This research study aims to investigate the educational needs of primary care physicians regarding opioid therapy and opioid use in pain management. METHODS: A computer-assisted web interview (CAWI) protocol was used to collect data from primary care physicians. Drug selection criteria, knowledge of opioid substitutes and dosage, and practical use of opioid therapy were evaluated. RESULTS: While 84% of participating physicians (724 respondents) reported initiating opioid treatment, only a minority demonstrated accurate opioid dosage calculations. Significant discrepancies between physicians' self-perceived knowledge and their clinical skills in opioid prescribing and pain management were observed. In total, 41% of physicians incorrectly indicated dose conversion rates for tramadol (the most frequently used drug according to 65% of responders). CONCLUSIONS: Targeted educational programs are essential to bridge the knowledge gap and increase physicians' competence in pain management. The proper self-assessment of one's own skills may be the key to improvement. Further research should focus on developing specialized educational courses and decision-support tools for primary care physicians and examining the impact of interprofessional pain management teams on patient outcomes.

Palliative medicine specialist and general practitioner interactions: national survey.

OBJECTIVES: The purpose of the study was to investigate the collaboration between primary care and palliative care physicians, which is key to providing comprehensive care, and to identify potential difficulties and needs in referring patients to palliative care. METHODS: The study was conducted as an online survey, available to primary care and palliative care physicians. The data collected during the survey were used to compare perceptions of different specialty physicians' perspectives on various aspects regarding palliative care. RESULTS: The results of the study showed significant differences in the assessment of the palliative care services availability (73% of primary care physicians rate it poorly comparing to high rating of 60% by palliative care specialists), as well as disparities between the declarations regarding the criteria used to decide on referral to palliative care (achieving the best quality of life) and the actual referral of patients (primary care physicians are third on the list of specialists referring patients to palliative care). Despite the need for adequate cooperation between family physicians and palliative care physicians, some difficulties were identified, such as primary care physicians' lack of knowledge of the patient palliative care referral criteria, and financial as well as personnel and palliative care facilities' limitations, were identified. CONCLUSIONS: The study confirms the need for better cooperation between primary care physicians and palliative care specialists in Poland. It suggests that educating primary care physicians about palliative care referral criteria can improve the patient referrals accuracy.

The Impact of Aerobic Exercise on HDL Quantity and Quality: A Narrative Review.

High-density lipoproteins comprise roughly 25-30% of the circulating proteins involved in the transport of lipids in circulation. These particles differ in size and lipid composition. Recent evidence suggests that the quality of HDL particles (which depends on shape, size and the composition of proteins and lipids determining HDL functionality) may be more important than their quantity. The functionality of HDL is mirrored by its cholesterol efflux activity, as well as its antioxidant (including the protection of LDL against oxidation), anti-inflammatory and antithrombotic properties. The results of many studies and meta-analyses imply the beneficial impact of aerobic exercise on HDL-C levels. Physical activity was found to be usually associated with an increase in HDL cholesterol and a decrease in LDL cholesterol and triglycerides. Exercise, apart from inducing quantitative alterations in serum lipids, exerts a beneficial impact on HDL particle maturation, composition and functionality. The Physical Activity Guidelines Advisory Committee Report underlined the importance of establishing a program recommending exercises that enable attainment of maximal advantage at the lowest level of risk. The aim of this manuscript is to review the impact of different types of aerobic exercise (various intensities and durations) on the level and quality of HDL.

Cardiotoxicity of Selected Vascular Endothelial Growth Factor Receptor Tyrosine Kinase Inhibitors in Patients with Renal Cell Carcinoma.

Renal cell carcinoma (RCC) is one of the most frequent malignant neoplasms of the kidney. The therapeutic options available for the treatment of advanced or metastatic RCC include vascular endothelial growth factor receptor (VEGFR)-targeted molecules, for example, tyrosine kinase inhibitors (TKI). Various VEGFR-TKIs proved to be effective in the treatment of patients with solid tumours. The combination of two drugs may prove most beneficial in the treatment of metastatic RCC; however, it also enhances the risk of toxicity compared to monotherapy. Specific VEGFR-TKIs (e.g., sunitinib, sorafenib or pazopanib) may increase the rate of cardiotoxicity in metastatic settings. VEGF inhibitors modulate multiple signalling pathways; thus, the identification of the mechanism underlying cardiotoxicity appears challenging. VEGF signalling is vital for the maintenance of cardiomyocyte homeostasis and cardiac function; therefore, its inhibition can be responsible for the reported adverse effects. Disturbed growth factor signalling pathways may be associated with endothelial dysfunction, impaired revascularization, the development of dilated cardiomyopathy, cardiac hypertrophies and altered peripheral vascular load. Patients at high cardiovascular risk at baseline could benefit from clinical follow-up in the first 2-4 weeks after the introduction of targeted molecular therapy; however, there is no consensus concerning the surveillance strategy.

Carotenoids in Palliative Care-Is There Any Benefit from Carotenoid Supplementation in the Adjuvant Treatment of Cancer-Related Symptoms?

Carotenoids are organic, liposoluble pigments found in nature, which are responsible for the characteristic colors of ripe tomatoes, carrots, peppers, and crustaceans, among others. Palliative care provided to patients with an incurable disease is aimed at improving the patient's quality of life through appropriate treatment of symptoms accompanying the disease. Palliative care patients with burdensome symptoms related to advanced-stage cancers are especially interested in the use of natural dietary supplements and herbal remedies to reduce symptoms' intensity and ameliorate the quality of life. Carotenoids seem to be a group of natural compounds with particularly promising properties in relieving symptoms, mainly due to their strong antioxidant, anti-inflammatory, and neuroprotective properties. Moreover, carotenoids have been used in folk medicine to treat various diseases and alleviate the accompanying symptoms. In this narrative review, the authors decided to determine whether there is any scientific evidence supporting the rationale for carotenoid supplementation in advanced-stage cancer patients, with particular emphasis on the adjuvant treatment of cancer-related symptoms, such as neuropathic pain and cancer-related cachexia.

Long-term analgesic pharmacotherapy in addiction to intranasal fentanyl.

OBJECTIVE: The risk of inappropriate use of opioid drugs increases, especially the short-acting ones. The risk of addiction in patients with cancer with a relatively good prognosis is a challenge. The aim of the study is to evaluate the decision to continue therapy with a short-acting fentanyl. METHODS: The study concerns a 49-year-old male patient with an advanced neuroendocrine tumour in the pre-sacral region. The research method includes the medical history and physical examination, an analysis of the patient's medical record and a self-designed questionnaire to assess the degree of dependence on opioid drugs. RESULTS: The analysis of the results of the survey confirmed the patient's dependence on opioid drugs. He gave positive answers to 16 out of 19 questions in the survey. CONCLUSION: Despite an addiction, the improvement of life quality is of the utmost importance. Therefore, decision to continue the intranasal fentanyl therapy is justified because of toleration and a high satisfactory effect.

Diabetes and Cardiovascular Risk in Renal Transplant Patients.

End-stage kidney disease (ESKD) is a main public health problem, the prevalence of which is continuously increasing worldwide. Due to adverse effects of renal replacement therapies, kidney transplantation seems to be the optimal form of therapy with significantly improved survival, quality of life and diminished overall costs compared with dialysis. However, post-transplant patients frequently suffer from post-transplant diabetes mellitus (PTDM) which an important risk factor for cardiovascular and cardiovascular-related deaths after transplantation. The management of post-transplant diabetes resembles that of diabetes in the general population as it is based on strict glycemic control as well as screening and treatment of common complications. Lifestyle interventions accompanied by the tailoring of immunosuppressive regimen may be of key importance to mitigate PTDM-associated complications in kidney transplant patients. More transplant-specific approach can include the exchange of tacrolimus with an alternative immunosuppressant (cyclosporine or mammalian target of rapamycin (mTOR) inhibitor), the decrease or cessation of corticosteroid therapy and caution in the prescribing of diuretics since they are independently connected with post-transplant diabetes. Early identification of high-risk patients for cardiovascular diseases enables timely introduction of appropriate therapeutic strategy and results in higher survival rates for patients with a transplanted kidney.

High-Dose Vitamin C in Advanced-Stage Cancer Patients.

High-dose intravenously administered vitamin C (IVC) is widely used in cancer patients by complementary and alternative medicine practitioners. The most frequent indications for IVC therapy result from the belief in its effectiveness as a potent anti-cancer agent which additionally enhances chemosensitivity of cancer cells and reduces chemotherapy-related toxicities and fatigue intensity. In this narrative review, we decided to deal with this issue, trying to answer the question whether there is any scientific evidence supporting the rationale for application of high-dose IVC therapy in advanced-stage cancer patients. Although results obtained from preclinical studies demonstrated that millimolar ascorbate plasma concentrations achievable only after IVC administration were cytotoxic to fast-growing malignant cells and inhibited tumor growth as well as prolonged the survival of laboratory animals, such positive effects were not found in human studies with advanced-stage cancer patients. We also have not found the rationale for the use of IVC to increase the effectiveness of chemotherapy and to reduce the chemotherapy-induced toxicity in the above mentioned group. Nevertheless, in palliative care, high-dose IVC might be considered as a therapy improving the quality of life and reducing cancer-related symptoms, such as fatigue and bone pain. However, because of the absence of placebo-controlled randomized trials on IVC efficacy in advanced-stage cancer patients, the placebo effect cannot be excluded.

Topical morphine for treatment of cancer-related painful mucosal and cutaneous lesions: a double-blind, placebo-controlled cross-over clinical trial.

INTRODUCTION: Painful mucosal and cutaneous lesions are often less responsive or even refractory to systemic opioid analgesics. There is evidence suggesting that the effectiveness of topical morphine be restricted to inflammatory pain. The studied groups were small and the observation period relatively short. The aim of this study was to assess the effectiveness and safety of topical morphine for pain related to mucosal lesions and skin ulcers. MATERIAL AND METHODS: The study was a 14-day randomized placebo-controlled cross-over trial (RCT) with a 28-day follow-up open phase (OP). The trial was conducted in adult patients with localized cancer-related pain and treated with systemic opioids in an oncology center or home hospice. The patients administered 0.2% gel on the mucosal lesion or 0.2% ointment on the skin lesion by themselves, without restrictions regarding the number of doses per day. The primary measurements were mean pain intensity (MPI) and mean pain relief (MPR) on the numeric rating scale (NRS 0-10), and ITT analysis was performed. RESULTS: Thirty-five patients were randomized to the RCT, and all of them completed 14-day observation. The MPI before the treatment was NRS 5.9 and decreased to 2.5 after morphine (p < 0.0001 vs. placebo). The MPR was 57% after morphine, and 77% of the patients using topical morphine obtained clinically significant (at least 50% of the starting value) pain relief, statistically different from placebo. The analgesic effect was sustained over the 28-day OP period (p = 0.00001). There were only 2 cases of moderate pruritus, and no other side effects were reported. CONCLUSIONS: Topical morphine was found to be a fast acting, highly effective, and safe medication for mucosal and skin lesions in palliative patients, with a sustainable pain relief effect over the 28-day observation period.

The occurrence and risk factors of constipation in inpatient palliative care unit patients vs. nursing home residents.

INTRODUCTION: Constipation is one of the most frequent clinical and nursing problems both in palliative care patients and in nursing home residents. AIM: To assess the occurrence of constipation and its risk factors in adult inpatient palliative care units versus nursing homes. MATERIAL AND METHODS: An epidemiological study was performed in an inpatient hospice and a nursing home. RESULTS: Fifty-one hospice patients and 49 nursing home residents were included in the study. Cancer was the main clinical condition in 90% of the palliative care patients (PCPs), and dementia or other psychotic disorders were predominant in the nursing home residents (NHRs). More PCPs had constipation than did NHRs (80% vs. 59%; p = 0.02), although none of the single constipation symptoms differed statistically between these two groups. The insufficient food intake was twice as severe in the hospice patients (p = 0.0001). 68.6% of PCPs took strong opioids, while none of the NHRs did. Three times more NHRs spent at least 50% of daytime in bed than did PCPs (73.5% vs. 23.5%; p < 0.0001). CONCLUSIONS: Constipation is very frequent in both palliative care patients and nursing home residents, but PCPs are more prone to it. The NHR and PCR groups should not be treated uniformly as the end-of-life population, referring to prevention and treatment of constipation, therapy needs, and the means enrolled for optimal symptom control.

Impact of Vitamin D on the Cardiovascular System in Advanced Chronic Kidney Disease (CKD) and Dialysis Patients.

In patients suffering from chronic kidney disease (CKD), the prevalence of cardiovascular disease is much more common than in the general population. The role of vitamin D deficiency had been underestimated until a significant association was found between vitamin D therapy and survival benefit in haemodialysis patients. Vitamin D deficiency is present even in the early stages of chronic kidney disease. The results of experimental studies have revealed the relationship between vitamin D deficiency and impairment of cardiac contractile function, higher cardiac mass and increased myocardial collagen content. Experimental models propose that intermediate end points for the relationship between vitamin D deficiency and higher risk of cardiovascular disease comprise diminished left ventricular hypertrophy (LVH), enhanced left ventricular diastolic function, and decreased frequency of heart failure. Multiple observational studies have demonstrated an association between the use of active vitamin D therapy in patients on dialysis and with CKD and improved survival. However, there are also many studies indicating important adverse effects of such treatment. Therefore, large randomized trials are required to analyze whether supplementation of vitamin D may affect outcomes and whether it is safe to be used in CKD patients.

The role and function of HDL in patients with diabetes mellitus and the related cardiovascular risk.

BACKGROUND: Diabetes mellitus (DM) is a major public health problem which prevalence is constantly raising, particularly in low- and middle-income countries. Both diabetes mellitus types (DMT1 and DMT2) are associated with high risk of developing chronic complications, such as retinopathy, nephropathy, neuropathy, endothelial dysfunction, and atherosclerosis. METHODS: This is a review of available articles concerning HDL subfractions profile in diabetes mellitus and the related cardiovascular risk. In this review, HDL dysfunction in diabetes, the impact of HDL alterations on the risk diabetes development as well as the association between disturbed HDL particle in DM and cardiovascular risk is discussed. RESULTS: Changes in the amount of circulation lipids, including triglycerides and LDL cholesterol as well as the HDL are frequent also in the course of DMT1 and DMT2. In normal state HDL exerts various antiatherogenic properties, including reverse cholesterol transport, antioxidative and anti-inflammatory capacities. However, it has been suggested that in pathological state HDL becomes "dysfunctional" which means that relative composition of lipids and proteins in HDL, as well as enzymatic activities associated to HDL, such as paraoxonase 1 (PON1) and lipoprotein-associated phospholipase 11 (Lp-PLA2) are altered. HDL properties are compromised in patients with diabetes mellitus (DM), due to oxidative modification and glycation of the HDL protein as well as the transformation of the HDL proteome into a proinflammatory protein. Numerous studies confirm that the ability of HDL to suppress inflammatory signals is significantly reduced in this group of patients. However, the exact underlying mechanisms remains to be unravelled in vivo. CONCLUSIONS: The understanding of pathological mechanisms underlying HDL dysfunction may enable the development of therapies targeted at specific subpopulations and focusing at the diminishing of cardiovascular risk.

Novel Biomarkers in the Diagnosis of Chronic Kidney Disease and the Prediction of Its Outcome.

In its early stages, symptoms of chronic kidney disease (CKD) are usually not apparent. Significant reduction of the kidney function is the first obvious sign of disease. If diagnosed early (stages 1 to 3), the progression of CKD can be altered and complications reduced. In stages 4 and 5 extensive kidney damage is observed, which usually results in end-stage renal failure. Currently, the diagnosis of CKD is made usually on the levels of blood urea and serum creatinine (sCr), however, sCr has been shown to be lacking high predictive value. Due to the development of genomics, epigenetics, transcriptomics, proteomics, and metabolomics, the introduction of novel techniques will allow for the identification of novel biomarkers in renal diseases. This review presents some new possible biomarkers in the diagnosis of CKD and in the prediction of outcome, including asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA), uromodulin, kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), miRNA, ncRNA, and lincRNA biomarkers and proteomic and metabolomic biomarkers. Complicated pathomechanisms of CKD development and progression require not a single marker but their combination in order to mirror all types of alterations occurring in the course of this disease. It seems that in the not so distant future, conventional markers may be exchanged for new ones, however, confirmation of their efficacy, sensitivity and specificity as well as the reduction of analysis costs are required.

The Effect of Diet on the Survival of Patients with Chronic Kidney Disease.

The prevalence of chronic kidney disease (CKD) is high and it is gradually increasing. Individuals with CKD should introduce appropriate measures to hamper the progression of kidney function deterioration as well as prevent the development or progression of CKD-related diseases. A kidney-friendly diet may help to protect kidneys from further damage. Patients with kidney damage should limit the intake of certain foods to reduce the accumulation of unexcreted metabolic products and also to protect against hypertension, proteinuria and other heart and bone health problems. Despite the fact that the influence of certain types of nutrients has been widely studied in relation to kidney function and overall health in CKD patients, there are few studies on the impact of a specific diet on their survival. Animal studies demonstrated prolonged survival of rats with CKD fed with protein-restricted diets. In humans, the results of studies are conflicting. Some of them indicate slowing down of the progression of kidney disease and reduction in proteinuria, but other underline significant worsening of patients' nutritional state, which can be dangerous. A recent systemic study revealed that a healthy diet comprising many fruits and vegetables, fish, legumes, whole grains, and fibers and also the cutting down on red meat, sodium, and refined sugar intake was associated with lower mortality in people with kidney disease. The aim of this paper is to review the results of studies concerning the impact of diet on the survival of CKD patients.

Accessibility of opioid analgesics and barriers to optimal chronic pain treatment in Poland in 2000-2015.

PURPOSE: Based on the international reports, consumption of opioid analgesics in Poland is relatively low. There is limited information on possible impediments to optimal opioid use. This study was aimed to identify possible barriers to access to opioid analgesics and causes of failure to comply with current clinical guidelines. METHODS: Consumption data per capita in 2000-2015 were analyzed in terms of oral morphine equivalents in total, per prescription type, per reimbursement status, to identify the impact of regulations specific for Poland. RESULTS: The consumption of opioid analgesics has been consistently growing from 36.0 in 2000 to 103.4 mg oral morphine equivalents (OME) per capita in 2015, mainly thanks to strong opioid consumption growth. Tramadol is the most commonly used opioid in Poland. Fentanyl and buprenorphine transdermal formulations are the most frequently used strong opioid analgesics in terms of OME. The vast majority (92.8 %) of opioids were distributed upon for outpatient use in 2015, with a almost fourfold growth of consumption of strong opioids and almost threefold of weak opioids between 2000 and 2015. Strong opioids were 41 % of OME used upon prescription in 2015. Acceleration of consumption growth has been observed since 2013. CONCLUSIONS: The prescription pattern does not abide by the current clinical guidelines for pain treatment, and the most often used opioids in Poland are tramadol, buprenorphine, and fentanyl. The use of opioids in Poland grows fast, with acceleration since 2013. The most important legal impediments of optimal opioid analgesics use have been lack of reimbursement, special prescription forms, and complicated prescribing rules.

How much does care in palliative care wards cost in Poland?

INTRODUCTION: The main task of palliative care units is to provide a dignified life for people with advanced progressive chronic disease through appropriate symptom management, communication between medical specialists and the patient and his family, as well as the coordination of care. Many palliative care units struggle with low incomes from the National Health Fund (NHF), which causes serious economic problems. The aim of the study was to estimate of direct and administrative costs of care and the actual cost per patient per day in selected palliative care units and comparison of the results to the valuation of the NHF. MATERIAL AND METHODS: The study of the costs of hospitalization of 175 patients was conducted prospectively in five palliative care units (PCUs). The costs directly associated with care were recorded on the specially prepared forms in each unit and also personnel and administrative costs provided by the accounting departments. RESULTS: The total costs of analyzed units amounted to 209 002 EUR (898 712 PLN), while the payment for palliative care services from the NHF amounted to 126 010 EUR (541 844 PLN), which accounted for only 60% of the costs incurred by the units. The average cost per person per day of hospitalization, calculated according to the actual duration of hospitalization in the unit, was 83 EUR (357 PLN), and the average payment from the NHF was 52.8 EUR (227 PLN). Underpayment per person per day was approximately 29.2 EUR (125 PLN). CONCLUSIONS: The study showed a significant difference between the actual cost of palliative care units and the level of refund from the NHF. Based on the analysis of costs, the application has been submitted to the NHF to change the reimbursement amount of palliative care services in 2013.

The Problem of Atrial Fibrillation in Patients with Chronic Kidney Disease.

Chronic kidney disease (CKD) is associated with the risk of multiple life-threatening complications such as: progression to chronic renal failure and cardiovascular disease including coronary heart disease, heart failure and peripheral arterial disease. Also, atrial fibrillation (AF) is common in this group of patients. Factors contributing to the occurrence of AF in patients undergoing dialysis include: age, presence of coronary heart disease, echocardiographic abnormalities (low ejection fraction, atrial enlargement, valvular calcification, left ventricular hypertrophy), heart failure, chronic obstructive pulmonary disease, hypertension, stroke, malnutrition (low levels of albumin, total cholesterol and high-density lipoprotein (HDL), secondary hyperparathyroidism, low predialysis systolic blood pressure, duration of renal replacement therapy as well as the method of renal replacement therapy (more frequent in haemodialysis patients). The optimal management of thromboprophylaxis in patients with CKD and AF is complex due to the fact that in patients with CKD many physiologic mechanisms are altered which lead to substantial changes in haemostasis and thus this group of patients is characterized by an increased risk of thrombotic and haemorrhagic complications. Recommendations concerning the treatment of patients with AF do not include guidelines on how to manage patients with advanced CKD, due to the lack of large randomized trials assessing the efficacy and benefits of drugs in these patients. Patients with CKD and permanent, persistent, and paroxysmal AF ought to be treated as a group with high risk of bleeding and ischaemic stroke. In case of patients with no or only one moderate risk factors, it seems that anticoagulation with antiplatelet drugs can be considered as efficient therapy, while in patients with ≥2 risk factors an oral anticoagulation therapy may be used. During long-term treatment, the international normalized ratio (INR) must be controlled at least every 14 days and adjusted within a target range of 2.0-2.5. Moreover, renal function should be evaluated before initiation of direct thrombin or factor Xa inhibitors and re-evaluated when clinically indicated and at least annually.

Behavioral risk factors of constipation in palliative care patients.

BACKGROUND: Constipation is frequently encountered in palliative care patients and remains a significant therapeutic problem. The etiology of constipation is multifactorial. Nutritional and behavioral factors are considered common causes of constipation; however, their impact has not yet been assessed precisely. OBJECTIVE: The aim of this study was to assess the correlation between the frequency of bowel movements (FoBM) and risk factors of constipation in palliative care patients. DESIGN AND SUBJECTS: A cohort retrospective study was performed in three palliative care centers, including outpatient, home, and inpatient care cancer patients using questionnaires on bowel dysfunction symptoms, behavioral risk factors, and opioid use. The inclusion criterion was adult patients examined on the day of admission. The exclusion criterion was Karnofsky performance status score ≤20. MEASUREMENTS: Spearman's rank correlation coefficient was used to measure the statistical dependence between two variables and frequency analysis was performed using the chi-squared test and Fisher's exact test. RESULTS: Two hundred thirty-seven valid questionnaires were collected. We found the correlation between FoBM and insufficient food and fluid intake (p < 0.0001), as well as for inadequate conditions of privacy (p = 0.0008), dependency on a caregiver (p = 0.0059), and the patient's overall performance status (p = 0.013). We did not manage to prove bed rest as the independent risk factor of constipation. CONCLUSIONS: The main risk factors of constipation in palliative care patients appeared to be insufficient fluid and food intake, inadequate conditions of privacy, dependency on a caregiver, as well as poor general performance status.

The AgNORs count in predicting long-term survival in serous ovarian cancer.

INTRODUCTION: The value of argyrophilic nucleolar organizer regions (AgNORs) to predict survival in patients with ovarian cancer has not been clearly explained yet. The aim of study was to assess the value of analysis of the mean number of AgNORs per nucleus (mAgNOR) and mean percentage of nuclei with five or more AgNORs per nucleus (pAgNOR) in the prediction of disease-free survival (DFS) and overall survival (OS) in patients with serous ovarian cancer. MATERIAL AND METHODS: The study examined 52 patients treated for serous ovarian cancer with a follow-up period of 2-143 months. After silver staining paraffin specimens from primary surgery, mAgNOR and pAgNOR in cancer cells were counted and analyzed. Age, grading, radicality of surgery and FIGO staging were analyzed as covariates. RESULTS: Mean mAgNOR equaled 4.4 ±0.9 and pAgNOR equaled 42.2 ±20.8%. Both mAgNOR and pAgNOR were the lowest in G1 tumors. The mAgNOR and pAgNOR were lower in stage I than stage IV cancers. The DFS and OS rates were respectively 15.4% and 21.2%. In univariate analysis FIGO staging, grading, and pAgNOR were associated with worse prognosis, while radicality of surgery remained a significant protective factor in terms of DFS. Higher FIGO staging and older age worsened OS. In multivariate analysis FIGO staging remained significantly associated with both DFS (HR 1.98; 95% CI 1.05-3.71) and OS (HR 1.76; 95% CI 1.00-3.10), while age affected OS rates (HR 1.78; 95% CI 1.04-2.95). CONCLUSIONS: mAgNOR and pAgNOR are useful markers of cellular kinetics. Prospective studies in larger populations are needed to confirm these results in terms of AgNORs' effects on survival.

Assessment of the argyrophilic nucleolar organizer region area/nucleus ratio in ovarian serous epithelial adenomas, borderline tumors and cancers.

INTRODUCTION: There is a need to assess the value of the novel potentially useful biomarkers in ovarian tumors. The aim of study was to assess the value of sAgNOR analysis in ovarian serous epithelial tumors. MATERIAL AND METHODS: The analysis was performed in ovaries from 113 patients treated operatively due to serous ovarian tumors (30 adenomas, 14 borderline tumors and 69 cancers). After silver staining of paraffin specimens from surgery, sAgNOR in tumor cells was analyzed. Additionally, the value of the argyrophilic nucleolar organizer region area/nucleus ratio (sAgNOR) in the prediction of disease-free survival (DFS) and overall survival (OS) in 52 patients with serous ovarian cancer with complete follow-ups in November 2009 was evaluated. Age, grading, radicality of surgery and FIGO staging were analyzed as additional factors. RESULTS: SAGNOR IN ADENOMAS, BORDERLINE TUMORS AND CANCERS WAS IN THE FOLLOWING RANGES: (0.73 ±0.23) × 10(6), (0.81 ±0.18) × 10(6) and (0.96 ±0.33) × 10(6) [AgNOR/cm(2)] respectively. In cancers from G1 to G3 sAgNOR was (1.02 ±0.32) × 10(6) (G1), (0.98 ±0.37) × 10(6) (G2) and (0.82 ±0.24) × 10(6) (G3) [AgNOR/cm(2)] respectively. In univariate analysis, but not in multivariate analysis, staging negatively correlated with better DFS and OS. sAgNOR, age of patients, grading and radicality of surgery were not associated with DFS or OS in either univariate or multivariate analysis. CONCLUSIONS: sAgNOR analysis is not sufficient to precisely characterize cellular kinetics in serous ovarian tumors, and the analysis of sAgNOR, mAgNOR and pAgNOR should be performed commonly. The prognostic significance of sAgNOR in patients with serous ovarian cancer was not proven.