Pelvic Organ Prolapse Reconstruction with the Chitosan-Based Novel Haemostatic Agent in Ovine Model-Preliminary Report.

This prospective study aimed to assess the feasibility of chitosan biomaterial and subcutaneous gel implantation in an ovine model, with implications for women with genital prolapse. Twenty-four ewes were divided into four groups (n = 6 per group): chitosan type B, chitosan type C, chitosan unmodified injections, and polypropylene mesh. Ovine models were chosen due to their morphological resemblance to human reproductive organs. Animals were sacrificed after 90 days for macroscopic, pathomorphological, and immunohistochemical analysis. In the chitosan type B group, IL-6 and IL-10 levels decreased after 28 days, while chitosan type C and injection groups exhibited higher IL-6 than IL-10 levels. The polypropylene group displayed the highest IL-6 and lowest IL-10 levels. Histological examination of the polypropylene group revealed no degenerative changes or inflammation, whereas chitosan injection induced local inflammation. Other groups exhibited no degenerative changes. Ewes implanted with chitosan displayed reduced inflammation compared to polypropylene-implanted ewes. Chitosan implantation facilitated vaginal tissue healing, in contrast to polypropylene mesh, which led to extrusion. While chitosan holds promise as an alternative to polypropylene mesh, further research is imperative for comprehensive evaluation. This study suggests the potential of a chitosan biomaterial in pelvic organ prolapse treatment, warranting additional investigation.

Transcriptome analysis of human Leydig cell tumours reveals potential mechanisms underlying its development.

Leydig cell tumours are the most common sex cord-stromal tumours. In the last years, apparent increased incidence is noted while aetiology of the tumour is still unknown. Therefore, here, we focused on the genetics of Leydig cell tumours using the next-generation sequencing. Leydig cell micronodules were revealed in patients with azoospermia who were qualified for testicular biopsy. Complete gene set of Leydig cell tumours was compared with transcriptome of healthy Leydig cells obtained from donors. Bioinformatic analysis of the obtained sequencing data revealed alterations in expression of 219 transcripts. We showed, for the first time, that a significant proportion of differentially expressed genes is directly involved in regulation of apoptotic process, which downregulation might be important to Leydig cell tumour development. Additionally, we found a significant upregulation of heat shock protein genes that might be a unique feature of Leydig cell tumours when compared to other tumour types. Our study offers fundamental transcriptomic data for future studies on human Leydig cell tumour that are crucial to determine its causes. Moreover, presented here the in-depth analysis and discussion of alterations observed in tumour transcriptome may be important for the diagnosis and therapy of this pathology.

Interstitial Leydig Cell Tumorigenesis-Leptin and Adiponectin Signaling in Relation to Aromatase Expression in the Human Testis.

Although epidemiological studies from the last years report an increase in the incidences of Leydig cell tumors (previously thought to be a rare disease), the biochemical characteristics of that tumor important for understanding its etiology, diagnosis, and therapy still remains not completely characterized. Our prior studies reported G-protein coupled estrogen receptor signaling and estrogen level disturbances in Leydig cell tumors. In addition, we found that expressions of multi-level-acting lipid balance- and steroidogenesis-controlling proteins including peroxisome proliferator-activated receptor are altered in this tumor. In order to get deeper into the other molecular mechanisms that regulate lipid homeostasis in the Leydig cell tumor, here we investigate the presence and expression of newly-described hormones responsible for lipid homeostasis balancing (leptin and adiponectin), together with expression of estrogen synthase (aromatase). Samples of Leydig cell tumors (n = 20) were obtained from patients (31-45 years old) and used for light and transmission electron microscopic, western blotting, and immunohistochemical analyses. In addition, body mass index (BMI) was calculated. In tumor mass, abundant lipid accumulation in Leydig cells and various alterations of Leydig cell shape, as well as the presence of adipocyte-like cells, were observed. Marked lipid content and various lipid droplet size, especially in obese patients, may indicate alterations in lipid homeostasis, lipid processing, and steroidogenic organelle function in response to interstitial tissue pathological changes. We revealed significantly increased expression of leptin, adiponectin and their receptors, as well as aromatase in Leydig cell tumors in comparison to control. The majority of patients (n = 13) were overweight as indicated by their BMI. Moreover, a significant increase in expression of phospholipase C (PLC), and kinases Raf, ERK which are part of adipokine transductional pathways, was demonstrated. These data expand our previous findings suggesting that in human Leydig cell tumors, estrogen level and signaling, together with lipid status, are related to each other. Increased BMI may contribute to certain biochemical characteristics and function of the Leydig cell in infertile patients with a tumor. In addition, altered adipokine-estrogen microenvironment can have an effect on proliferation, growth, and metastasis of tumor cells. We report here various targets (receptors, enzymes, hormones) controlling lipid balance and estrogen action in Leydig cell tumors indicating their possible usefulness for diagnostics and therapy.

Assessment of selected quality of life domains in patients who have undergone conservative or radical surgical treatment for penile cancer: an observational study.

Background Surgery is the standard treatment for organ-restricted penile cancer, but it is also a disfiguring procedure that can profoundly affect quality of life. Using a survey, in this study we assessed the effect of different surgical invasiveness on satisfaction in selected life domains of patients who underwent penile-sparing surgery and partial penectomy. METHODS: Forty patients who underwent penile-sparing surgery (n=13) or partial penectomy (n=27) were enrolled in the study. The response rate was 71%. Information was obtained after surgery on sexuality, self-esteem, masculinity and partner relationships using the International Index of Erectile Function, the Self-Esteem Scale and the Conformity to Masculinity Norms Inventory questionnaires. We evaluated the effect of primary surgery type on selected domains of quality of life and correlations between study variables after surgery. RESULTS: High self-esteem, satisfactory erectile function and masculinity results in both groups were comparable to those in the published literature. Men who underwent less disfiguring treatment had a significantly higher sense of masculinity than those who underwent partial penectomy (P=0.05). No significant differences were observed in erectile dysfunction and self-esteem. The level of aggressiveness of a surgical procedure was a predictor of sense of masculinity (P=0.01), but was not associated with self-esteem and sexual dysfunction (P=0.28 and P=0.55 respectively); 83% of patients were able to satisfactorily maintain partner relationships. CONCLUSIONS: Disfiguring treatments for penile cancer significantly interfere with the sense of masculinity, but sexual functioning and self-esteem do not differ according to the type of surgical procedure. Most men maintained stable partner relationships after surgery, regardless of surgery type.

Assessment of quality of life in patients surgically treated for penile cancer: Impact of aggressiveness in surgery.

PURPOSE: Health-related quality of life (HRQoL) evaluations are being increasingly used for clinical assessment of cancer treatment outcomes. For a patient, not only is life expectancy important, but also a general sense of sustained global health. Intuitively, the more disfiguring the treatment, the more pronounced could be the deterioration in the QoL. We aimed to compare various aspects of QoL in three groups of patients surgically treated for penile cancer by local excision, partial penectomy, or total penectomy. METHODS: HRQoL was assessed in 51 patients surgically treated for penile cancer. Total penectomy, partial penectomy, or wide local excision was performed in 11, 27, and 13 patients, respectively. The EORTC QLQ-C30 questionnaire was used for HRQoL assessment. Relations between the patients and their partners were also assessed. RESULTS: Statistically significant negative correlation was found between aggressiveness of the surgical procedure and both, assessment of global health status (p = 0.04) and physical functioning (p = 0.047). The more aggressive the surgery, the lower was the patients' assessment of their QoL. Among the patients who maintained their partner relations postsurgery, 58.9% declared that their relations postoperatively were not inferior compared to those preoperatively. There was no statistically significant effect of the surgery type on relations with female partners (p = 0.619). CONCLUSION: The magnitude of disfigurement caused by surgical treatment of penile cancer had a significant impact on the selected QoL domains assessed by the EORTC QLQ C-30 questionnaire. There was no correlation between the scope of surgical intervention and partner relations.

Basic issues concerning health-related quality of life.

INTRODUCTION: Chronic diseases such as cancer have a strong influence on both physical health and quality of life, which together comprise the concept of health-related quality of life (HRQoL) - in other words, the complete state of physical, social, and psychological functioning. Herein, we review the literature on the theory of HRQoL in relation to oncological diseases. MATERIAL AND METHODS: A literature search of English-language publications that included an analysis of the conceptual models of HRQoL was performed using PubMed. The data were screened and synthesized by all authors and relevant papers were selected. RESULTS: We outline the theoretical models most often used to conceptualize HRQoL, including the Centre for Health Promotion model from the University of Toronto, the conceptual model of Wilson and Cleary and the contextual model of Ashing-Giwa formulated specifically for cancer patients. CONCLUSIONS: Understanding the theoretical basis of HRQoL is indispensable for valid research in this area.

Quality of life in penile carcinoma patients - post-total penectomy.

INTRODUCTION: Total amputation, as a treatment for advanced penile cancer, significantly debilitates the patient's quality of life and sexual function. The aim of the study was to assess the quality of life in patients who had undergone total penectomy. MATERIAL AND METHODS: The questionnaires EORTC QLQ C-30, SES, CMNI, and a modified IIEF-15 questionnaire, were sent to 11 patients. RESULTS: A total of 10 patients returned the questionnaires completed. The results of the overall quality of life, the median result in individual domains, as assessed by the EORT QLQ C-30 questionnaire, were clearly lower than the reference results. There were statistically significant differences in the results of the QLQ C-30, concerning the role-functioning domain in relation to age (p = 0.008) and education (p = 0.032), in the domain of emotional functioning in relation to education (p = 0.008) and in the domains of physical functioning in relation to the partner relationship (p = 0.032). A significant number of patients were sexually inactive. Sexual activity as defined by touching the area of the pubic symphysis at the scars of the penis, touching and fondling perianal areas or the scrotum and watching things/people that cause excitement was observed in 2/10, 1/10 and 2/10 of patients respectively. In 5/6 of these patients, partnership relationships did not deteriorate, including one patient for whom the relationship actually improved. CONCLUSIONS: The results obtained indicate that total amputation of the penis significantly affects one's sex life and overall quality of life. However, this does not have negative implications in terms of partnership relations, self-assessment or the evaluation of masculinity.

Primary penile cancer organ sparing treatment.

INTRODUCTION: Surgical treatment of penile cancer is usually associated with mutilation; alterations in self-esteem and body image; affecting sexual and urinary functions; and declined health-related quality of life. Recently, organ sparing treatment has appeared and led to limiting these complications. MATERIAL AND METHODS: An extensive review of the literature concerning penile-preserving strategies was conducted. The focus was put on indications, general principles of management, surgical options and reconstructive techniques, the most common complications, as well as functional and oncological outcomes. RESULTS: Analyzed methods, e.g.: topical chemotherapy, laser ablation therapy, radiotherapy, Moh's microscopic surgery, circumcision, wide local excision, glans resurfacing and glansectomy are indicated in low-stage tumors (Tis, Ta-T2). After glansectomy, reconstruction is also possible. CONCLUSIONS: Organ sparing techniques may achieve good anatomical, functional, and psychological outcomes without compromising local cancer control, which depends on early diagnosis and treatment. Penile sparing strategies are acceptable treatment approaches in selected patients with low-stage penile cancer after establishing disease-risk and should be considered in this population.

The risk of neoplasm associated with dysgenetic testes in prepubertal and pubertal/adult patients.

INTRODUCTION: In patients with Y-chromosome in the karyotype, partial gonadal dysgenesis and disorders of male reproductive sex organs development are usually resected in childhood because of the high risk of germ cell tumours (GCT). In patients with Y-chromosome, complete gonadal dysgenesis and female genitalia gonadectomy is performed markedly later. However, due to the relatively low number of adult patients with preserved dysgenetic gonads, the true risk of neoplasm is unknown. The aim of the study was to evaluate the prevalence of neoplasia in dysgenetic gonads of children and adults with Y-chromosome in a retrospective study. MATERIAL AND METHODS: A review of medical documentation of 94 patients with disorders of sex development (DSD), Y-chromosome and gonadal dysgenesis (GD), aged 1.2-32 years (47 prepubertal, 1.2-10 years; 47 pubertal/adult, 13-32 years), was conducted. Serum levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH) and testosterone were determined. Bilateral gonadectomy was performed in 73.4% of patients, and unilateral gonadectomy with biopsy of the contralateral gonad in 26.4%. All gonadal tissues were subjected to immunohistochemical evaluation with antibodies against PLAP and OCT3/4 (markers of malignant germ cells, but also foetal multipotent germ cells), while gonads of prepubertal patients were examined by c-KIT, as well. RESULTS: Streak gonads were identified on both sides (complete GD) in 30.8%, a streak gonad on one side and an underdeveloped testis on the other (asymmetric GD) in 38.3%, and underdeveloped testicular structure on both sides (partial GD) in 30.8% of cases. Germ cell neoplasia was found in 53.2% of patients (51.1% in children, 55.3% in pubertal/adults). Invasive GCT were identified in 11.7% of cases, of which 90.9% were in pubertal/adult patients. Other neoplastic lesions included gonadoblastoma (16% prevalence) and testicular carcinoma in situ (25.5%). In younger patients FSH serum levels were increased in 81% of cases (mean 2.82 ± 2.18 IU/L), while LH in 58% (mean 1.82 ± 1.69 IU/L). Hypergonadotropic hypogonadism was diagnosed in most of the pubertal/ /adult patients (mean FSH 54.2 ± 23.3 IU/L, mean LH 21.7 ± 12.1 IU/L, mean testosterone 5.5 ± 4.5 nmol/L). CONCLUSIONS: Dysgenetic gonads in patients with Y chromosome have a high risk of germ cell neoplasia (ca. 50%). If they are preserved until puberty/early adulthood, they may develop overt, invasive GCT. The gonads also have poor hormonal activity (hypergonadotropic hypogonadism) in most of the pubertal/adult patients. Each of these cases must be considered individually and a decision to remove the gonad or not should be based on the comprehensive analysis of the phenotype by a multidisciplinary team of specialists in consultation with the patient and the parents. If dysgenetic gonads are not resected in childhood, these patients need careful ongoing follow-up examination, including biopsy and histopathological evaluation.

FISH and array CGH characterization of de novo derivative Y chromosome (Yq duplication and partial Yp deletion) in an azoospermic male.

This study presents a 28-year-old infertile male who was referred to the cytogenetic laboratory for chromosomal analysis after 4 years of regular unprotected intercourse in whom non-obstructive azoospermia was revealed. Standard cytogenetic G-banding was performed on metaphase spreads and a de-novo karyotype 46,X,der(Y)(q11.22;p11.3) was identified. This analysis was followed by flourescence in-situ hybridization(FISH) and array comparative genomic hybridization (aCGH). Finally, the patient's karyotype was identified as 46,X,der(Y)(qter→q11.221::p11.31→qter).ish der(Y) (qter+,pter-,SHOX+,SRY+,Ycen+,DYZ3+;DYZ1+,qter+).arrYq11.221q12(14,448,863-59,288,511) x2, Yp11.32p11.31(104,062-266,388) x0. It is proposed that de-novo derivative monocentric Y chromosome with duplicated region Y qter→q11.221::p11.31→qter with partial deletion of Yp PAR1 region most probably can perturb the conjugation of sex chromosomes during first meiotic division of spermatogenic arrested differentiation (development).

Pre-analytical-related variability influencing serum peptide profiles demonstrated in a mass spectrometry-based search for colorectal and prostate cancer biomarkers.

Although the degradome, which comprises proteolytic fragments of blood proteins, presents a potential source of diagnostic biomarkers, studies on cancer peptide biomarkers have provided inconsistent conclusions. In the present study, we reevaluated the usefulness of serum degradome analyses for searching peptide cancer biomarker candidates. Particular attention was paid to pre-analytical factors influencing the variability of determined peptide levels, including clotting time and control group selection. Studies were conducted on 44 and 86 serum samples collected from cancer patients and healthy individuals, respectively, using liquid chromatography electrospray ionization mass spectrometry (LC-ESI-MS)-based analyses. We identified 1373 unique peptides, nearly 40% of which originated from five blood proteins: fibrinogen alpha chain, apolipoprotein A-IV (APOA4), complement C3, apolipoprotein A-I, and alpha-1-antitrypsin. A set of 118 and 88 peptides exhibited highly significant differences (adjusted p-value ≤ 0.01 and fold change ≥ 2) in pair-wise comparisons of control vs. prostate cancer and control vs. colorectal cancer, respectively, with 37 peptides displaying a consistent direction of change for these pair-wise comparisons. The levels of 67 peptides differed significantly in serum samples collected from healthy individuals immediately prior to colonoscopy and those who underwent colonoscopic examination at least four weeks earlier. Of them, 49 peptides originated from APOA4. Whereas earlier studies, including ours, have utilized fragments of fibrinopeptide A (FPA) to distinguish cancer from healthy cases, here we show that their absolute abundance is a sensitive indicator of clotting time. These observations may have implications for future serum peptidome studies since these issues have not previously been recognized.

[Children born from frozen embryos stored for 10 years -- analysis of 5 cases]. / Dzieci urodzone z zarodków przechowywanych w stanie zamrozenia przez 10 lat. Analiza 5 przypadków.

Faced with a scientific and legal debate on human embryo cryopreservation in Poland we show 5 documented clinical cases of successful thawing and transfer of embryos cryopreserved for a long period of time (8-11 years), resulting in successful delivery by the biological or the recipient mother. Cases described include patients with different infertility diagnoses, subjected to different hormonal stimulation treatments. Different oocyte fertilization methods were performed, and the obtained embryos were frozen after 2, 3 or 4 days of in vitro culture using methods employing various cryoprotective agents and freezing curves. As a result of performed thawing and transfer procedures normal, healthy babies were born. Our results are consistent with the international reports on successful long-term storage of embryos, (including the longest known period of over 19 years) resulting in no detectable reduction of the developmental potential after thawing. In light of data shown here, we do not see any medical or biological reasons for legally-regulated limitation of the period of frozen embryo storage. Moreover, if frozen, long-term stored embryos are not threatened by destruction and if prenatal adoption is a real, clinically documented option, we fail to see any reason for legal limitations of embryo cryopreservation in human infertility treatment.

The role of oxidative stress and antioxidants in male fertility.

Oxidative stress results from the imbalance between production of the reactive oxygen species (ROS) and the protective effect of the antioxidant system responsible for their neutralization and removal. An excess of ROS causes a pathological reaction resulting in damage to cells and tissues. Spermatozoa are particularly vulnerable to the harmful effects of ROS. Oxidative stress affects their activity, damages DNA structure, and accelerates apoptosis, all of which consequently decrease their numbers, hinders motility and development of normal morphology, and impairs function. This leads to disturbances in fertility or embryo development disorder. The main cellular source of ROS in the semen are immature sperm cells and white blood cells. The increase in the number of leukocytes may be due to infection and inflammation, but can also be secondary to harmful environmental factors, long sexual abstinence, or varicocele. The protective antioxidant system in the semen is composed of enzymes, as well as nonenzymatic substances, which closely interact with each other to ensure optimal protection against ROS. Non-enzymatic antioxidants include vitamins A, E, C, and B complex, glutathione, pantothenic acid, coenzyme Q10 and carnitine, and micronutrients such as zinc, selenium, and copper. It seems that a deficiency of any of them can cause a decrease in total antioxidant status. In vitro and in vivo that studies demonstrate many antioxidants possess a beneficial effect on fertility and, therefore, their use is recommended as supportive therapy for the treatment of infertility in men.

Pooled sample-based GWAS: a cost-effective alternative for identifying colorectal and prostate cancer risk variants in the Polish population.

BACKGROUND: Prostate cancer (PCa) and colorectal cancer (CRC) are the most commonly diagnosed cancers and cancer-related causes of death in Poland. To date, numerous single nucleotide polymorphisms (SNPs) associated with susceptibility to both cancer types have been identified, but their effect on disease risk may differ among populations. METHODS: To identify new SNPs associated with PCa and CRC in the Polish population, a genome-wide association study (GWAS) was performed using DNA sample pools on Affymetrix Genome-Wide Human SNP 6.0 arrays. A total of 135 PCa patients and 270 healthy men (PCa sub-study) and 525 patients with adenoma (AD), 630 patients with CRC and 690 controls (AD/CRC sub-study) were included in the analysis. Allele frequency distributions were compared with t-tests and χ(2)-tests. Only those significantly associated SNPs with a proxy SNP (p<0.001; distance of 100 kb; r(2)>0.7) were selected. GWAS marker selection was conducted using PLINK. The study was replicated using extended cohorts of patients and controls. The association with previously reported PCa and CRC susceptibility variants was also examined. Individual patients were genotyped using TaqMan SNP Genotyping Assays. RESULTS: The GWAS selected six and 24 new candidate SNPs associated with PCa and CRC susceptibility, respectively. In the replication study, 17 of these associations were confirmed as significant in additive model of inheritance. Seven of them remained significant after correction for multiple hypothesis testing. Additionally, 17 previously reported risk variants have been identified, five of which remained significant after correction. CONCLUSION: Pooled-DNA GWAS enabled the identification of new susceptibility loci for CRC in the Polish population. Previously reported CRC and PCa predisposition variants were also identified, validating the global nature of their associations. Further independent replication studies are required to confirm significance of the newly uncovered candidate susceptibility loci.

Urinary incontinence after radical prostatectomy - experience of the last 100 cases.

Radical prostatectomy (RP) is a recognized treatment method of organ-confined prostate cancer. Among post-surgery complications, urinary incontinence is a major one. The aim of this study was to determine the incontinence rate after RP and to analyze factors that might affect it. Between March 2007 and December 2008, 132 RP's were performed at Warsaw Cancer Center. A questionnaire to assess the condition before and after RP was developed by the authors and sent to all treated patients. The questionnaire focused on health status information, function in urinary domain, rate of returning to "normal" activity level as before RP and satisfaction from the treatment. The median age of patients was 62 years. Out of 132 patients 102 subjects (77.2%) responded to the questionnaire. Of all responders, 35 patients (34.3%) reported total urinary continence after RP. After RP 35(34.3%) patients reported total urinary continence and in 55(53.9%) patients urinary incontinence of medium degree was present. In 12 (11.8%) patients significant urinary incontinence developed. The most common cause of urine dripping (82% of patients with any degree of urinary incontinence) was associated with abdominal muscle pressure. No statistically significant association between urinary incontinence and adjuvant radiotherapy after RP or the surgeon performing the RP was found (>0.79, >0.803). Radical prostatectomy carries a certain risk of complications. We observed an 88.2% rate of significant (total and moderate degree) urinary continence. The adjuvant radiotherapy and surgeons, who performed the RP, did not affect the rate of incontinence.

Molecular analysis of defects in the CFTR gene and AZF locus of the Y chromosome in male infertility.

OBJECTIVE: To investigate the frequency and potential impact of mutations and polymorphisms in the CFTR gene and deletions in AZF locus of the Y chromosome in patients with azoospermia (AZOO), cryptozoospermia (CRYPTO) or oligoasthenoteratozoospermia (OAT) who were to be included in an assisted reproductive technologies (ART) program. STUDY DESIGN: A total of 188 infertile men were enrolled in the study: 100 patients with AZOO, 38 with CRYPTO and 50 with OAT. RESULTS: The CFTR gene mutations or IVS8-5T variant in at least 1 allele was identified with similar frequencies among the AZOO (33%) and CRYPTO (21%) patients; 55% of the AZOO patients with normal spermatogenesis (NS) had mutations in 1 or 2 alleles. The novel R810G mutation in exon 13 was identified in 1 NS patient. The OAT or AZOO patients with Sertoli cell only syndrome (SCO) had mutations in the CFTR gene with similar frequencies to that in the general Polish population. The deletions in the AZF locus were detected in 20% of SCO patients, 11.5% of AZOO patients with maturation arrest and in 5% of CRYPTO patients. The other groups (NS, OAT) did not carry deletions in the region studied. CONCLUSION: Molecular diagnosis of the CFTR gene, Y chromosome deletion analysis and genetic counseling are necessary diagnostic elements for patients with male infertility, especially if the are included in an ART program.