Aleksandra Ciałkowska-Rysz

Increased Levels of Soluble TNF-α Receptors and Cellular Adhesion Molecules in Patients Undergoing Bioincompatible Hemodialysis

Background: The study aimed to differentiate the effects of hemodialysis (HD) and chronic renal failure (CRF) on the levels of circulating tumor necrosis factor-α (TNF-α) and TNF-α receptors p55 and p75, soluble vascular cell adhesion molecule-1 (sVCAM-1), intercellular adhesion molecule-1 (sICAM-1), soluble endothelial-leukocyte adhesion molecule-1 (sE-selectin) and sP-selectin in 18 patients on regular HD treatment with cuprophane membrane in relation to 15 non-dialyzed CRF patients and 15 healthy controls. Methods: The serum concentrations were determined with standard ELISA assays. Results: Blood serum p75 and p55 were approximately tenfold increased in CRF (36.7 ± 6.2 and 27.1 ± 5.6 ng/ml) and HD patients (45.6 ± 18.4 and 28.7 ± 5.9 ng/ml) before the HD session (HD 0), during (HD 20) the session (45.7 ± 18.4 and 28.5 ± 7.3 ng/ml) and after (HD 240) the HD session (52.1 ± 17.4 and 30.9 ± 8.2 ng/ml) in comparison to control values (5.6 ± 1.3 and 2.4 ± 0.8 ng/ml, respectively) (p < 0.01). The highest increment of p75 at the end of HD session (HD 240) was also significantly higher than at preceding time points (HD 0 and 20) (p < 0.05). However, the remaining study parameters did not change during an HD session. Also, there were no relevant changes in TNF-α levels if (HD 0) 22.7 ± 21.5 ng/ml and (HD 240) 21.1 ± 18.9 ng/ml were compared. Chronic HD status was related to the increase of sVCAM-1 and sICAM-1 levels. Prior to HD, T0 sVCAM-1 and sICAM-1 concentrations were 2,180.4 ± 761.8 and 567.3 ± 218.8 ng/ml, during HD (T20): 2,172.7 ± 759.2 and 602.3 ± 379.9 ng/ml, and after HD (T240): 2,401.6 ± 756.4 and 648.3 ± 183.5 ng/ml, respectively (p < 0.05 vs. controls and CRF patients). sVCAM-1 and sICAM-1 serum levels (1,262.2 ± 472.9 and 165.6 ± 50.4 ng/ml) were similar in CRF patients and healthy controls (854.4 ± 241.5 and 217.6 ± 74.2 ng/ml, respectively). Even though serum sE- and sP-selectin in CRF patients did not differ from the control (39.8 ± 21.3 vs. 42.1 ± 18.9 ng/ml and 187.9 ± 66.9 vs. 198.8 ± 62.2 ng/ml, respectively), their levels were increased in HD patients up to 111.9 ± 54.6 and 453.2 ± 231.1 ng/ml in patients prior to HD, 118.7 ± 66.2 and 350.8 ± 114.8 ng/ml during the HD session and then 132.3 ± 61.1 and 368.3 ± 126.6 ng/ml, respectively, after its completion (p < 0.05 in comparison with CRF patients and controls). Conclusions: The increased circulating TNF-α receptors appear more associated with the uremic milieu than HD-related systemic inflammation, whereas increased soluble cellular adhesion molecules in patients undergoing bioincompatible HD may be related to the enhanced systemic inflammation specifically due to maintenance HD.

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.

Long-term survival of endometrioid endometrial cancer patients

Introduction To establish risk factors for onset and progression of endometrioid endometrial cancer still remains the aim of scientists. The aim of the study was to determine disease-free survival (DFS) and overall survival (OS) in women with endometrioid endometrial cancer. Material and methods A retrospective review of 142 patients with endometrioid endometrial cancer after surgery treated with adjuvant radiotherapy and/or chemotherapy in the Regional Cancer Centre in Lodz between 2002 and 2004 was performed. Clinical and pathological data were correlated with clinical outcome and survival. Results In 3 patients (2.1%) clinical progression was diagnosed during the treatment. In 23 patients (16.7%) after primary remission, relapse was diagnosed 2-56 months after treatment. DFS and OS were 81.7% and 83.1% respectively. Better DFS significantly correlated with larger number of pregnancies (> 1), stage I of the disease and optimal surgery. Lower stage of disease, pelvic lymph node dissection, optimal surgery and depth of myometrial infiltration ≤ 50% were independent prognostic factors for better OS. Conclusions The results of our study provided significant evidence that early detection of endometrioid endometrial cancer enables optimal surgery. It reduces the indications for adjuvant therapy in stage I of the disease, and makes the prognosis significantly better. Other clinical and pathological factors such as numerous pregnancies, pelvic lymphadenectomy, and depth of myometrial infiltration, although important, are of less significance. Further prospective, randomized studies are necessary to prove the role of these factors.

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.

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.

Behavioral risk factors of constipation in palliative care patients

BackgroundConstipation 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.ObjectiveThe 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 subjectsA 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.MeasurementsSpearman’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.ResultsTwo 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.ConclusionsThe 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.

Personal fear of death affects the proper process of breaking bad news

Introduction Breaking bad news may be affected not only by insufficient knowledge of a physician, but also by his attitude, religious beliefs, fears, lack of experience, etc. This survey was aimed to test the relation between physicians’ fear of own death and philosophy of life and their inclination to break bad news. Material and methods One hundred seventy students of the last year of medical faculty filled in a 4-item questionnaire created by the authors. The participants were asked on their opinion on whether to inform patients on upcoming death, as well as fear of their own death and willingness to receive bad news. The last question was aimed to distinguish the respondents based on their determination in philosophy of life. Results Ninety-three percent of respondents think that patients should be informed about unfavorable prognosis but only 86% would like to be informed about their own upcoming death. There is a negative correlation between determination of philosophy of life and fear of own death (p = 0.024), but no correlation between fear of own death and the degree of religiousness (Fisher’s accurate p = 0.18). Persons determined to receive information on their own upcoming death are more prone to inform patients about their upcoming death (ρ = 0.31; p < 0.0001). Conclusions Personal fear of own death and low level of determination of philosophy of life may restrain medical professionals from breaking bad news to patients. Not only knowledge of the principles, but also personal attitude should be addressed in the curriculum of physician-patient communication education.

Primary uterine rhabdomyosarcoma in a patient with a history of breast cancer and gastrointestinal stromal tumor

We describe a unique case of a 67‐year‐old patient with primary uterine rhabdomyosarcoma with a history of breast cancer and gastrointestinal stromal tumor of the stomach. Uterine rhabdomyosarcoma was diagnosed in our patient during adjuvant treatment of breast cancer with anastrozole. To the best of our knowledge, the development of primary uterine rhabdomyosarcoma has never been described in patients treated with anastrozole. Due to the suggested causative role of tamoxifen in the development of uterine sarcomas, it is interesting to analyze whether the new drug, anastrozole, exerts any pathogenic effect on the development of uterine sarocomas.

The comparison of common cancer types and the coincidence of concomitant chronic diseases between palliative home care patients in Lodz Voivodeship and the general Polish population.

Introduction The continued growth in the number of elderly with cancer and age-related chronic diseases will cause in Poland an increase in demand for palliative care. The aim of the study was to identify chronic comorbidities and cancer types in palliative home care patients and to compare their incidence with the general Polish population. Material and methods The data was obtained from 543 patients who received palliative home care between 2005-2009. The occurrence of the most common chronic conditions such as arterial hypertension, ischemic heart disease, diabetes, chronic pulmonary diseases and central nervous system diseases were analysed together with the cancer types. Results The study group included 259 women (47.7%) and 284 men (52.3%) aged 25-91 years old. The most common primary neoplasm locations for men were lung (28.2% vs. 21.4% in general population) and colorectal cancer (18.7% vs. 11.4% in general population), and in women breast (19.7% vs. 22.8% in general population) and colorectal cancer (17.4% vs. 9.2% in general population). The incidence of ischemic heart disease, diabetes, and chronic pulmonary diseases was significantly different in comparison to the general populations (47.0% vs. 11.3%; 20.3% vs. 6.8%; 16.6% vs. 27.5%, respectively). The mean number of concomitant diseases was 1.6 for women and 1.8 for men vs. 1.7 and 1.2 in the general Polish population respectively. Conclusions The majority of the patients had concomitant disease, with cardiovascular diseases being most common. The most common primary neoplasm diagnoses in palliative home care patients were lung and colorectal cancer, which corresponds to the cancer prevalence in the general population.

Isolated metastasis to the foot as an extremely rare presenting feature of primary endometrial cancer.

Endometrial cancer is the most common invasive cancer of the female genital tract, with an increasing incidence rate. Abnormal uterine bleeding is the presenting symptom in 75-90% of cases [1, 2]. The majority of patients with endometrial cancer are diagnosed with no evidence of extra-uterine spread (70-80% stage I), which gives patients better prognosis [1, 3]. In more advanced disease the sites commonly affected outside the uterus are pelvic and para-aortic lymph nodes and the ovaries [4]. Similarly to uterine sarcomas, distant metastases in advanced or recurrent endometrial cancer most commonly involve the lungs, liver, central nervous system and skin [4–6]. Metastases to bones have been described in 2-15% of patients with metastatic disease, and the most common site of osseous metastases are vertebrae, with pelvic bones, ribs and sternum [3, 7]. Isolated metastases to bone extremities are extremely rare, and thought to result from the haematological spread of cancer cells [5]. The review of the Medline database by searching the items endometrial cancer and metastases to extremities showed twenty such cases, with only nine cases when metastatic tumour of the foot was the first manifestation of endometrial cancer (Table I) [3, 5, 7–13]. Table I Isolated metastasis to the bones of the extremities as the first manifestation of endometrial cancer – review of the literature A 74-year-old female suffered from pain and swelling of the right foot from October 2006. In the X-ray picture and bone scintigraphy, suspected lesion of the right calcaneus, talus and metatarsal bones was detected (Figure 1). Afterwards it was histologically verified in the biopsy as metastatic cancer (Figure 2). The patient had no vaginal bleeding or other gynaecological symptoms, but subsequent computed tomography scans showed an enlarged uterus. Uterine curettage confirmed the diagnosis of endometrial cancer. The patient was treated with total abdominal hysterectomy, bilateral salpingo-oophorectomy without pelvic lymph node dissection in December 2006. The histological diagnosis was a moderate differentiated (G2) endometrioid endometrial cancer invading the outer half of the myometrium (> 1/2) with invasion of cervical stroma. The fallopian tubes and the ovaries showed no signs of metastases. No evidence of macroscopic abdominopelvic metastases was found at surgery. Her disease was classified as clinical stage IVB according to FIGO 2009 staging, but in the TNM classification it was pT2 Nx M2. Figure 1 Radiograph of the right foot demonstrating metastases of the endometrial cancer Figure 2 Metastatic endometrial cancer cells in the fine needle aspiration of the tumour of the foot (H + E, 200× magnification) In January 2007 the patient was admitted to the department of palliative radiotherapy. She received irradiation by Co 60 until a total dose of 20 Gy to the tumour of the right foot, with complete resolution of symptoms. The patient was discharged from hospital in March 2007. During the observation from surgery in December 2006 until June 2010 no other metastases were detected. The patient remains alive and asymptomatic 43 months after the diagnosis of metastatic endometrial cancer to the foot. Our report presented in the previous section has three main peculiar features: 1) it demonstrates endometrial cancer that presented with osseous metastasis, which is a rare occurrence, 2) the metastatic tumour was located in the foot, which is extremely rare, 3) the bone lesion was a single bone metastasis, which is unusual in such cases. Additionally, the case in which isolated metastatic tumour of the extremity was the first manifestation of endometrial cancer is the tenth such case reported in the literature (Table I), and the second one located in the calcaneus and involving talus and metatarsal bones [8]. Despite the rarity of metastases to the upper and lower extremities, there is a need to have a high index of suspicion for metastasis in patients with a history of endometrial cancer who present with swelling or bony tenderness. The initial diagnosis can be challenging, as the symptoms of pain and swelling are often attributed to other more common benign conditions such as soft tissue inflammation, trauma, arthritis, and osteomyelitis [7]. It is important to consider bone metastasis as a possible diagnosis also in patients without history of cancer, but with osseous pain not responding to conservative treatment [5, 9–13]. Appropriate imaging may include plain X-ray picture and radionuclide bone scans [3]. Technetium diphosphonate bone scans can be positive up to 18 months before a lesion is detectable on plain X-ray [14]. Therefore, a biopsy should be performed in patients with suspected lesions, and who demonstrate evidence of bony destruction [4]. The treatment strategy in patients with confirmed isolated metastatic lesion in the bone extremity still remains a topic of controversy, because of the few descriptions available in the literature and the different bone sites involved. For these reasons, a common suitable treatment regimen cannot be established and treatment should be tailor suited to each patient. The treatment of irradiation with or without surgery, hormone therapy and chemotherapy is reported as effective in most cases and may be curative [4, 5, 7, 9, 11, 12]. The main goal of treatment should be to eliminate or palliate pain and prolong survival.