Tumor location matters, next generation sequencing mutation profiling of left-sided, rectal, and right-sided colorectal tumors in 552 patients.

Despite the introduction of new molecular classifications, advanced colorectal cancer (CRC) is treated with chemotherapy supplemented with anti-EGFR and anti-VEGF targeted therapy. In this study, 552 CRC cases with different primary tumor locations (250 left side, 190 rectum, and 112 right side) were retrospectively analyzed by next generation sequencing for mutations in 50 genes. The most frequently mutated genes were TP53 in left-sided tumors compared to right-sided tumors and BRAF in right-sided tumors compared to left-sided tumors. Mutations in KRAS, NRAS, and BRAF were not detected in 45% of patients with left-sided tumors and in 28.6% of patients with right-sided tumors. Liver metastases were more common in patients with left-sided tumors. Tumors on the right side were larger at diagnosis and had a higher grade (G3) than tumors on the left. Rectal tumors exhibit distinctive biological characteristics when compared to left-sided tumors, including a higher absence rate of KRAS, NRAS, and BRAF mutations (47.4% in rectal versus 42.8% in left-sided tumors). These rectal tumors are also unique in their primary metastasis site, which is predominantly the lungs, and they have varying mutation rates, particularly in genes such as BRAF, FBXW7, and TP53, that distinguish them from tumors found in other locations. Primary tumor location has implications for the potential treatment of CRC with anti-EGFR therapy.

Changes in survival of colorectal cancer patients in Swietokrzyskie Province (Southern Poland) from the second half of the 1990s to the early 21st century - a population-based study.

INTRODUCTION AND OBJECTIVES: For years, the increase in cancer incidence and deaths has constituted a significant health and social problem. Variation in the burden in cancers in different regions of the world requires constant monitoring of the epidemiological situation in this regard. Assessing survival in cancer patients is a valuable source of information for patients and physicians alike, as well as for politicians who have a direct impact on the shaping of health policy and health systems. The aim of the present study was to assess the changes in the 5-year relative survival of colorectal cancer patients during 1995-2014. MATERIAL AND METHODS: The data of 8,970 patients with colorectal cancer in the years 1995-2014, 5,033 males and 3,937 females aged 67.5 ± 11.7 from Swietokrzyskie Cancer Registry were used. Cases were classified according to the topographical codes ICD-O-3: C18.0-C18.9, C19.9, C20.9, C21.0-C21.2, C21.8. The end of follow-up was fixed at 31 December 2014. Four five-year calendar periods were defined. In each calendar period, relative survival rates using the Ederer II method were estimated separately for males and females. RESULTS: In 2010-2014 (against 1995-1999), the absolute increase in the 5-year relative survival in males and females with colon cancer was the highest and reached 9.8 percentage point (p.p.) and 9.6 p.p., respectively. Patterns of survival for both colon and rectal cancer patients according to gender and age were very similar. CONCLUSIONS: In 1995-2014, an increase in the value of relative survival rates of males and females with colorectal cancer was observed. Systematic increase in funding in health care was a chance for reducing the burden of colorectal cancer by more widespread and equal access of effective early detection and cancer treatment.

Age-Dependent Disparities in the Prevalence of Single and Clustering Cardiovascular Risk Factors: A Cross-Sectional Cohort Study in Middle-Aged and Older Adults.

BACKGROUND: Cardiovascular diseases (CVDs) are the leading cause of mortality worldwide; with age acknowledged as an independent cardiovascular risk factor (CRF) in adults. Appreciating the association between age and classic CRFs is believed to boost all potential benefits of prevention. PURPOSE: Assessment of the prevalence of single and clustered CRFs and their association with age. PATIENTS AND METHODS: The survey involved 4735 people (33.6% men) who were PONS project attendees aged 45-64. The study protocol comprised the Health Status Questionnaire, general medical examination, anthropometric measurements, and blood and urine sampling. The prevalence of single and clustered CRFs (hypertension, dyslipidemia, diabetes mellitus, and obesity) in the incrementally split age groups was calculated. The incidence rate of CRFs, against their absence, was determined by Poisson regression models with robust standard errors. RESULTS: The prevalence of CRFs was established in 90% of the respondents. Except dyslipidemia and ≥1 CRFs, prevalence of risk factors increased with age, although this trend was the weakest in men. In the total group, and in women, prevalence of dyslipidemia and ≥1 CRFs was unrelated to age, whereas in men, it was on the rise in the younger age groups. The incidence rate of CRFs was strongly related to age, and, with the exception of dyslipidemia, was higher in the older age groups. CONCLUSION: Cardiovascular risk factors are common in the adult population, while their prevalence and clustering are more prevalent in seniors. Apart from dyslipidemia, the risk of CRFs is appreciably age-related, and higher in seniors.

WHO recommendations on physical activity versus compliance rate within a specific urban population as assessed through IPAQ survey: a cross-sectional cohort study.

OBJECTIVE: The study was designed to address the following three key areas, that is, (1) evaluate overall level of physical activity in the residents of a mid-sized, Central-European city, (2) compliance level with WHO's recommendations on physical activity in leisure time and (3) actual impact of select socioeconomic factors on the physical activity level within the study population. METHODS: Assessment of the source data collected for 4619 participants (1532 men and 3087 women, aged 45-65 years; mean age 56.41±5.31 years) was completed. Three levels of physical activity, and compliance level with pertinent WHO recommendations was evaluated, based on International Physical Activity Questionnaire (long form). Multilevel logistic regression models of socioeconomic factors associated with moderate-level, high-level physical activity, and WHO recommendations were developed. RESULTS: Data analyses revealed that 6.19% of the study participants (n=286) engaged in low-level physical activity, 48.86%-in moderate-level activity, while high-level activity was reported in 44.94% of them. Compliance with pertinent WHO recommendations was higher in men aged 44-55 years, boasting upper-level education, living without a partner and in the persons with a net income over €1140 per household. CONCLUSIONS: Overall level of physical activity in the residents of a mid-sized, Central-European city was established as moderate. Pertinent WHO recommendations on physical activity were met by 4.2% of the subjects only.

Vitamin D as a follicular marker of human oocyte quality and a serum marker of in vitro fertilization outcome.

PURPOSE: This study investigated the relationship between the vitamin D [25(OH)D] level in individual follicles and oocyte developmental competence. METHODS: A prospective cohort study in a private infertility center. Infertile women (N = 198) scheduled for intracytoplasmic sperm injection (ICSI) and a single embryo transfer (SET) provided serum samples and 322 follicular fluid (FF) specimens, each from a single follicle on the day of oocyte retrieval. RESULTS: FFs corresponding to successfully fertilized oocytes (following ICSI) contained significantly lower 25(OH)D level compared with those that were not fertilized (28.4 vs. 34.0 ng/ml, P = 0.001). Top quality embryos on the third day after fertilization, when compared to other available embryos, developed from oocytes collected from follicles containing significantly lower 25(OH)D levels (24.56 vs. 29.59 ng/ml, P = 0.007). Positive hCG, clinical pregnancy, and live birth rates were achieved from embryos derived from oocytes that grew in FF with significantly lower 25(OH)D levels than in follicles not associated with subsequent pregnancy. The concentration of 25(OH)D in FF in women with negative hCG was 32.23 ± 20.21 ng/ml, positive hCG 23.62 ± 6.09 ng/ml, clinical pregnancy 23.13 ± 6.09 ng/ml, and live birth 23.45 ± 6.11 ng/ml (P < 0.001). Women with serum 25(OH)D < 20 ng/ml had not only a higher fertilization rate (71 vs. 61.6%, P = 0.026) and a higher clinical pregnancy rate (48.2 vs. 25%, P = 0.001), but also higher miscarriage rate (14.5 vs. 3.8%, P = 0.013) compared with those with levels ≥ 20 ng/ml. CONCLUSION: This study reveals that the level of 25(OH)D in FF correlates negatively with the oocytes' ability to undergo fertilization and subsequent preimplantation embryo development. Oocytes matured in FF with low 25(OH)D concentration are more likely to produce top quality embryos and are associated with higher pregnancy and delivery rates. On the other hand, low serum vitamin D concentration is associated with higher miscarriage rates.

Reproductive outcomes of intracytoplasmic sperm injection (ICSI) in good-prognosis patients who electively decided to limit the number of oocytes used for microinjection: a two-center comparative study.

OBJECTIVES: The aim of the study was to compare the outcomes of intracytoplasmic sperm injection/embryo transfer (ICSI/ET) between two IVF centers with similar pregnancy rates and embryo transfer policy but with two different approaches to good-prognosis patients who intentionally chose to limit the number of oocytes used for ICSI. MATERIAL AND METHODS: It was a retrospective two-center comparative study A total of 218 patients after successful retrieval of >10 mature oocytes following ovarian hyperstimulation were included in the study The number of fertilized oocytes used during ICSI/ET was limited to 6 and 10 in 108 and 110 patients of the Centre for Reproductive Medicine KRIOBANK and VitroLive Fertility Clinic, respectively RESULTS: No significant differences in the implantation rate (29.93% vs. 29.54%; p=0.94) and ongoing pregnancy rate (39.81% vs. 45.45%, p=0.40) were observed between patients who electively fertilized 6 as compared to 10 oocytes, respectively However in patients who deliberately limited the number of fertilized oocytes to 6 the following were observed: i) significantly fewer embryos available for ET (2.89 ± 1.23 vs. 3.77 ± 1.48, p<0.0 1); ii) considerably lower number of frozen embryos per cycle (1.05 ± 1.30 vs. 2.00 ± 1.67, p<0.01), and iii) lower rates of cycles with embryo cryopreservation (4 7.22% vs. 72.72%, p<0.01) as compared to patients with 10 fertilized oocytes. CONCLUSIONS: Elective fertilization of 6 vs. 10 oocytes does not adversely affect fresh ICSI/ET outcome in normal-responding patients. Restricted number of oocytes used for ICSI/ET may be a favorable alternative for couples who do not wish to cryopreserve surplus human embryos.

Arachidonic and linoleic acid derivatives impact oocyte ICSI fertilization--a prospective analysis of follicular fluid and a matched oocyte in a 'one follicle--one retrieved oocyte--one resulting embryo' investigational setting.

OBJECTIVE: To evaluate human oocyte ability to undergo fertilization and subsequent preimplantation embryonic development in relation to a wide panel of follicular fluid (FF) arachidonic acid derivatives (AAD) and linoleic acid derivatives (LAD) of prospectively selected patients undergoing intracytoplasmic sperm injection (ICSI). METHODOLOGY: Study was designed as a two center (a university clinic and a private clinic) prospective study. 54 women of 181 consecutive couples undergoing ICSI were prospectively found to be eligible for analysis. 'One follicle - one retrieved oocyte - one resulting embryo' approach was used. Each individual follicle was aspirated independently and matched to an oocyte growing in this particular follicular milieu. FF samples were assessed for AAD and LAD by high-performance liquid chromatography; additionally, activity of secretory phospholipase A (sPLA2) was determined by enzyme-linked immunosorbent assay. PRINCIPAL FINDINGS: Increased activity of sPLA2 and significantly higher AAD and LAD levels were found in FF of oocytes that did not show two pronuclei or underwent degeneration after ICSI in comparison to oocytes with the appearance of two pronuclei. Receiver operating characteristics curve analysis identified acids with the highest sensitivity and specificity: 5oxo-hydroxyeicosatetraenoic, 16-hydroxyeicosatetraenoic, 9-hydroxyoctadecadieneoic and 12-hydroxyeicosatetraenoic. No significant differences between AAD and LAD related to embryo quality were found. CONCLUSIONS/SIGNIFICANCE: Our study demonstrates for the first time that elevated concentrations of AAD and LAD in FF at the time of oocyte retrieval significantly decrease the ability of oocytes to form pronuclei after ICSI. This may serve as a new tool for non-invasive assessment of oocyte developmental capacity. However, levels of AAD and LAD are not associated with subsequent embryo quality or pregnancy rate, and therefore more studies are needed to determine their usefulness in human IVF procedure.

Radiotherapy versus radiochemotherapy with cisplatin in treatment of cervical cancer.

AIM: To compare effects of concomitant radiochemotherapy (RCTh) and radiotherapy (RTh) alone in patients with cervical carcinoma and with 36-months follow-up analysis. MATERIAL AND METHODS: 106 stage IIA-IVA cervical carcinoma women were divided in two groups. RCTh group was treated with teleradiotherapy (50.4 Gy/T), intracavitary brachytherapy (46 Gy), and iv cisplatin (40 mg/m(2)). RTh group was treated with pelvic teletherapy (52-54 Gy/T) and intracavitary brachytherapy (50-55 Gy). RESULTS: In RCTh group absorbed radiation dose was significantly lower (50.4 vs. 52.7 Gy) and the duration of treatment was significantly shorter (45.1 days vs. 47.8 days). There were no statistical differences in both groups in survival (59% in RCTh group vs. 56% in RTh group), response to treatment (86% vs. 90%), local recurrence (42% vs. 49%) metastasis occurrence (21% vs. 17%), anemia (40% vs. 26%), early postradiation reactions in intestines (77% vs. 65%) and bladder (71% vs. 61%) as well as in incidence of rectovaginal (10% vs. 4%) and vesicovaginal formation of fistulas (6% vs. 4%), respectively. There were significant differences between two groups in: nausea (77% vs. 6%), vomiting (65% vs. 3.7%), leucopenia (69% vs. 26%) and thrombocytopenia (35% vs. 9%), and late postradiation bladder effects (94% vs. 74%). RCTh patients with anemia had lower 36-months survival rates (42% vs. 71%), more frequent local recurrences (77% vs. 31%) and metastasis-free survival rates (61% vs. 90%) than RCTh patients without anemia. CONCLUSIONS: RCTh gives better treatment results in patients without than in patients with anemia and higher overall survival rates than RTh in patients without anemia. The only clinical prognostic factor for advance cervical carcinoma is the clinical stage of the disease.

Comparison of embryological and clinical outcome in GnRH antagonist vs. GnRH agonist protocols for in vitro fertilization in PCOS non-obese patients. A prospective randomized study.

PURPOSE: Embryological and clinical efficacy of gonadotropin-releasing hormone (GnRH) antagonist and agonist stimulation protocols in non-obese women with polycystic ovarian syndrome (PCOS) were compared. METHODS: A prospective randomized study. SETTING: Medical University Hospital. PATIENTS: 70 infertile PCOS patients; 33 in GnRH antagonist and 37 in GnRH agonist group. RESULTS: Similar mature metaphase II oocyte rate (76% vs. 76%) was observed in both protocols. Optimal pronuclear morphology zygotes dominated in both groups (64% vs. 66%). Transferred embryo quality did not differ in both protocols. No significant differences between both protocols were found in delivery rate (p = 0.481), pregnancy rate (p = 0.810), multiple pregnancy rate (p = 0.501), miscarriage rate (p = 0.154), fertilization rate (p = 0.388) and implantation rate (p = 1.000). Duration of stimulation and total follicle-stimulating hormone (FSH) dose were significantly lower in GnRH antagonist protocol (p = 0.0005). CONCLUSIONS: GnRH antagonist and agonist protocols in non-obese PCOS patients yield similar embryological and clinical outcomes. Shorter duration of treatment and lower FSH requirement in GnRH antagonist group may be financially beneficial and therefore attractive for patients.

Isolated severe hydrothorax with respiratory distress as a main manifestation of ovarian hyperstimulation syndrome preceded by respiratory tract infection caused by Haemophilus influenzae.

INTRODUCTION: An isolated unilateral pleural effusion as the only presentation of ovarian hyperstimulation syndrome (OHSS) is very rare. This case is an unusual presentation of OHSS after a confirmed respiratory tract infection, with no other coexisting risk factors identified for this syndrome. We also imply that the presence of Haemophilus influenzae in bronchial fluid can increase local reaction to vasoactive cytokines. CASE REPORT: A 32-year-old woman presented at the Department of Reproductive Medicine and Gynaecology of the Pomeranian Medical University after 10 years of infertility with diagnosed hyperprolactinemia followed by bromocriptine treatment. The patient had three IUIs but no pregnancy was achieved. Therefore, ICSI was proposed. After an ovarian hyperstimulation, oocyte aspiration gave 8 oocytes. Although ICSI was performed in all of the oocytes there were 3 fertilizations. The ET of 3 embryos was carried out following 3 days of culture. Three weeks before the gonadotropin administration and a week before GnRH administration the patient had a respiratory tract infection with the most typical syndromes. The infection was treated successfully with over-the-counter medications and antibiotic. Three days after ET the patient was admitted to the ICU with signs of severe dyspnoea. The chest X-ray showed a large pleural effusion over the right lung. Upon admission, thoracocentesis was preformed and 1600 ml of clear fluid was aspirated. The bronchial aspirate showed evidence of Haemophilus influenzae and leukocytes. After three days of standard treatment the chest X-ray revealed no pathology. The patient was discharged asymptomatic on the 4th day of treatment. Serum beta-hCG level was negative on day 12 after ET. CONCLUSIONS: This case suggest that respiratory tract infection prior to stimulation may constitute a new independent risk factor for OHSS. However, the true relation between the respiratory tract infection and susceptibility to OHSS still awaits explanation. Recent or existing respiratory tract infection may be a relative contraindication for starting COH.

Biotechnological and clinical outcome of in vitro fertilization in non-obese patients with polycystic ovarian syndrome.

INTRODUCTION: Polycystic ovarian syndrome (PCOS) is a hormonal and metabolic disorder which poses problems with controlled ovarian stimulation (COH). It has been also postulated that PCOS patients have oocytes and embryos with poorer quality which affects IVF results. AIM: To verify IVF outcome in non-obese patients with PCOS. MATERIALS AND METHODS: IVF results of 71 non-obese PCOS patients with 243 non-obese non-POCS patients, regardless of stimulation protocol, from years 2004-2006 were compared. RESULTS: Biotechnological results of PCOS patients in opposition to non-PCOS patients were respectively as follows: higher average number (10.19 vs. 7.61; p=0.001) and percentage (82.34% vs. 76.25%; p=0.025) of retrieved mature M2 oocytes; similar (77.01% vs. 76.75%; p=0.835) fertilization rate with higher average number of embryos (7.633 vs. 5.650 p=0.003); higher average number (4.830 vs. 3.304; p=0.001) and percentage (65.66% vs. 60.57%; p=0.006) of embryos with optimal Z1 and Z2 pronuclei pattern according to Scott; higher average number of class Aembryos (3.57 vs. 2.34; p=0.001). Similar number of embryos were transferred in both groups (2.408 vs. 2.485, p=0.552). Clinical results in PCOS and non-PCOS patients were as follows: similar stimulation duration (10.53 days vs. 10.31 days; p=0.639) with significant less gonadotropin total usage (1866.54 IU vs. 2276.18 IU; p=0.001). Also clinical pregnancy per transfer (57.75% vs. 41.98%; p=0.021) and delivery per transfer (45.07% vs. 32.51%; p=0.066) were more often in PCOS patients with comparable miscarriages (12,68% vs. 6,58%; p=0.131) and ectopic pregnancy (0.00% vs. 2.06%; p=0.591) rates, respectively. CONCLUSION: PCOS in non-obese patients is linked with good biotechnological and clinical IVF outcome.