Expression of TRF2 and its prognostic relevance in advanced stage cervical cancer patients

BACKGROUND: Telomeres are protective caps consisted of specific tandem repeats (5′-TTAGGG-3′). Shortening of telomeres at each cell division is known as "mitotic clock" of the cells, which renders telomeres as important regulators of lifespan. TRF2 is one of the critical members of shelterin complex, which is a protein complex responsible from the preservation of cap structure, and loss or mutation of TRF2 results in DNA damage, senescence or apoptosis. Since cancer is frequently associated with aberrant cell cycle progression, defective DNA repair or apoptosis pathways, TRF2 could be one likely candidate for cancer therapy. Here we investigated the prognostic role of TRF2 levels in cervical cancer patients. Fold-induction rates were evaluated with respect to median values after real-time PCR analysis. Overall survival, distant disease-free and local recurrence-free survival rates were calculated using Kaplan-Meier long rank test. RESULTS: Both five year overall- and disease-free survival rates were longer in patients with higher TRF2 expression compared to lower expression, but results were not statistically significant (69.2% vs 28.9%, respectively). Mean local recurrence-free survivals (LRF) were very close ( 58.6, CI: 44.3-72.9 vs 54.5, CI: 32.1-76.9 months) for high and low expressions, respectively. Cumulative proportion of LRF at the end of five year period was 76.9% for high and 57.1% for low TRF2 expression (P = 0.75). Statistically significant difference was found between survival ratios and Bcl-xL and p53 gene expressions, but not with TRF2. A respectable correlation between TRF2 expression and apoptosis along with distant metastasis was noted (P = 0.045 and 0.036, respectively). Additionally, high TRF2 expression levels had a positive impact in five year survival rate of stage IIIB-IVA patients (P = 0.04). CONCLUSIONS: Our results support the role of TRF2 in apoptosis and imply a positive relation with distant metastases and survival in advanced stage patients. The remarkable difference in survival periods of patients with different TRF2 expressions suggest that TRF2 may be a candidate factor to estimate survival for cervical cancer, a preliminary observation which should further be verified with a larger cohort

Long-term effects of neoadjuvant chemoradiotherapy followed by sphincter-preserving resection on anal sphincter function in relation to quality of life among locally advanced rectal cancer patients: a cross-sectional analysis

BACKGROUND: There is growing recognition for the consequences of rectal cancer treatment to maintain an adequate functional sphincter in the long-term rather than preserving the anal sphincter itself. This study aims to evaluate long-term effects of neoadjuvant chemoradiotherapy (nCRT) followed by sphincter-preserving resection on anal sphincter function in relation to quality of life (QoL) among locally advanced rectal cancer patients. METHODS: Twenty-nine patients treated with nCRT followed by low anterior resection surgery were included in this study. Data on patient demographics, tumor location and symptoms of urgency and fecal soiling were recorded and evaluated with respect to Wexner Fecal Incontinence Scoring Scale, European Organization for Research and Cancer (EORTC) cancer-specific (EORTC QLQ-C30) and colorectal cancer-specific (EORTC QLQ-CR38) questionnaires and anorectal manometrical findings. Correlation of manometrical findings with Wexner Scale, EORTC QLQ-CR38 scores and EORTC QLQ-C30 scores was also evaluated. RESULTS: Median follow-up was 45.6 months (ranged 7.5–98 months. Higher scores for incontinence for gas (p = 0.001), liquid (p = 0.048) and solid (p = 0.019) stool, need to wear pad (p = 0.001) and alteration in life style (p = 0.004) in Wexner scale, while lower scores for future perspective (p = 0.010) and higher scores for defecation problems (p = 0.001) in EORTC QLQ-CR38 were noted in patients with than without urgency. Manometrical findings of resting pressure (mmHg) was positively correlated with body image (r = 0.435, p = 0.030) and sexual functioning (r = 0.479, p = 0.011) items of functional scale, while rectal sensory threshold (RST) volume (mL) was positively correlated with defecation problems (r = 0.424, p = 0.031) items of symptom scale in EORTC QLQ-CR38 and negatively correlated with social function domain (r = −0.479, p = 0.024) in EORTC QLQ-C30. RST volume was also positively correlated with Wexner scores including incontinence for liquid stool (r = 0.459, p = 0.024), need to wear pad (r = 0.466, p = 0.022) and alteration in lifestyle (r = 0.425, p = 0.038). CONCLUSION: The high risk of developing functional anal impairment as well as the systematic registration of not only oncological but also functional and QoL related outcomes seem important in rectal cancer patients in the long-term disease follow-up

Volume CXIV, Number 4, November 7, 1996

Objective: Turner syndrome (TS) is a chromosomal disorder caused by complete or partial X chromosome monosomy that manifests various clinical features depending on the karyotype and on the genetic background of affected girls. This study aimed to systematically investigate the key clinical features of TS in relationship to karyotype in a large pediatric Turkish patient population.Methods: Our retrospective study included 842 karyotype-proven TS patients aged 0-18 years who were evaluated in 35 different centers in Turkey in the years 2013-2014.Results: The most common karyotype was 45,X (50.7%), followed by 45,X/46,XX (10.8%), 46,X,i(Xq) (10.1%) and 45,X/46,X,i(Xq) (9.5%). Mean age at diagnosis was 10.2±4.4 years. The most common presenting complaints were short stature and delayed puberty. Among patients diagnosed before age one year, the ratio of karyotype 45,X was significantly higher than that of other karyotype groups. Cardiac defects (bicuspid aortic valve, coarctation of the aorta and aortic stenosis) were the most common congenital anomalies, occurring in 25% of the TS cases. This was followed by urinary system anomalies (horseshoe kidney, double collector duct system and renal rotation) detected in 16.3%. Hashimoto's thyroiditis was found in 11.1% of patients, gastrointestinal abnormalities in 8.9%, ear nose and throat problems in 22.6%, dermatologic problems in 21.8% and osteoporosis in 15.3%. Learning difficulties and/or psychosocial problems were encountered in 39.1%. Insulin resistance and impaired fasting glucose were detected in 3.4% and 2.2%, respectively. Dyslipidemia prevalence was 11.4%.Conclusion: This comprehensive study systematically evaluated the largest group of karyotype-proven TS girls to date. The karyotype distribution, congenital anomaly and comorbidity profile closely parallel that from other countries and support the need for close medical surveillance of these complex patients throughout their lifespa

Sex difference and intra-operative tidal volume: Insights from the LAS VEGAS study

BACKGROUND: One key element of lung-protective ventilation is the use of a low tidal volume (VT). A sex difference in use of low tidal volume ventilation (LTVV) has been described in critically ill ICU patients.OBJECTIVES: The aim of this study was to determine whether a sex difference in use of LTVV also exists in operating room patients, and if present what factors drive this difference.DESIGN, PATIENTS AND SETTING: This is a posthoc analysis of LAS VEGAS, a 1-week worldwide observational study in adults requiring intra-operative ventilation during general anaesthesia for surgery in 146 hospitals in 29 countries.MAIN OUTCOME MEASURES: Women and men were compared with respect to use of LTVV, defined as VT of 8 ml kg-1 or less predicted bodyweight (PBW). A VT was deemed 'default' if the set VT was a round number. A mediation analysis assessed which factors may explain the sex difference in use of LTVV during intra-operative ventilation.RESULTS: This analysis includes 9864 patients, of whom 5425 (55%) were women. A default VT was often set, both in women and men; mode VT was 500 ml. Median [IQR] VT was higher in women than in men (8.6 [7.7 to 9.6] vs. 7.6 [6.8 to 8.4] ml kg-1 PBW, P < 0.001). Compared with men, women were twice as likely not to receive LTVV [68.8 vs. 36.0%; relative risk ratio 2.1 (95% CI 1.9 to 2.1), P < 0.001]. In the mediation analysis, patients' height and actual body weight (ABW) explained 81 and 18% of the sex difference in use of LTVV, respectively; it was not explained by the use of a default VT.CONCLUSION: In this worldwide cohort of patients receiving intra-operative ventilation during general anaesthesia for surgery, women received a higher VT than men during intra-operative ventilation. The risk for a female not to receive LTVV during surgery was double that of males. Height and ABW were the two mediators of the sex difference in use of LTVV.TRIAL REGISTRATION: The study was registered at Clinicaltrials.gov, NCT01601223