BACKGROUND: The anatomic descriptions and extents of radical hysterectomy often vary across the literature and operative reports worldwide. The same nomenclature is often used to describe varying procedures, and different nomenclature is often used to describe the same procedure despite the availability of guideline and classification systems. This makes it difficult to interpret retrospective surgical reports, analyze surgical databases, understand technique descriptions, and interpret the findings of surgical studies. OBJECTIVE: In collaboration with international experts in gynecologic oncology, the purpose of this study was to establish a consensus in defining and interpreting the 2017 updated Querleu-Morrow classification of radical hysterectomies. STUDY DESIGN: The anatomic templates of type A, B, and C radical hysterectomy were documented through a set of 13 images taken at the time of cadaver dissection. An online survey related to radical hysterectomy nomenclature and definitions or descriptions of the associated procedures was circulated among international experts in radical hysterectomy. A 3-step modified Delphi method was used to establish consensus. Image legends were amended according to the experts' responses and then redistributed as part of a second round of the survey. Consensus was defined by a yes response to a question concerning a specific image. Anyone who responded no to a question was welcome to comment and provide justification. A final set of images and legends were compiled to anatomically illustrate and define or describe a lateral, ventral, and dorsal excision of the tissues surrounding the cervix. RESULTS: In total, there were 13 questions to review, and 29 experts completed the whole process. Final consensus exceeded 90% for all questions except 1 (86%). Questions with relatively lower consensus rates concerned the definitions of types A and B2 radical hysterectomy, which were the main innovations of the 2017 updated version of the 2008 Querleu-Morrow classification. Questions with the highest consensus rates concerned the definitions of types B1 and C, which are the most frequently performed radical hysterectomies. CONCLUSION: The 2017 version of the Querleu-Morrow classification proved to be a robust tool for defining and describing the extent of radical hysterectomies with a high level of consensus among international experts in gynecologic oncology. Knowledge and implementation of the exact definitions of hysterectomy radicality are imperative in clinical practice and clinical research.

• MeSH
• cervix uteri MeSH
• hysterektomie metody   MeSH
• konsensus MeSH
• lidé MeSH
• nádory ženských pohlavních orgánů * MeSH
• retrospektivní studie MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: Idiopathic bleeding in the second trimester of pregnancy complicates <1% of all pregnancies. This pregnancy complication can be caused by alterations in local hemostasis in the decidua due to infection/inflammation in the choriodecidual niche. This condition is associated with intraamniotic inflammatory complications. Antibiotic therapy effectively reduces the intensity of intraamniotic inflammation in certain pregnancy pathologies. However, whether antibiotic administration can reduce the intensity of the intraamniotic inflammatory response or eradicate microorganisms in patients with idiopathic bleeding during the second trimester of pregnancy remains unclear. OBJECTIVE: This study primarily aimed to determine whether antimicrobial agents can reduce the magnitude of intraamniotic inflammation in patients with idiopathic bleeding in the second trimester of pregnancy by assessing the concentration of interleukin-6 in the amniotic fluid before and after 7 days of antibiotic treatment. The secondary aim was to determine whether treatment with a combination of antibiotics altered the microbial load of Ureaplasma species DNA in amniotic fluid. STUDY DESIGN: This retrospective cohort study included singleton-gestation patients with idiopathic bleeding between 15+0 and 27+6 weeks who underwent transabdominal amniocentesis at the time of admission. Follow-up amniocentesis was performed in a subset of patients unless abortion or delivery occurred earlier. Concentrations of interleukin-6 were measured in the amniotic fluid samples, and the presence of microbial invasion of the amniotic cavity was assessed using culture and molecular microbiological methods. Intraamniotic inflammation was defined as an interleukin-6 concentration ≥3000 pg/mL in the amniotic fluid samples. RESULTS: A total of 36 patients with idiopathic bleeding in the second trimester of pregnancy were included. All the patients underwent initial amniocentesis. Patients with intraamniotic inflammation (n=25) were treated using a combination of antibiotics consisting of intravenous ceftriaxone, intravenous metronidazole, and peroral clarithromycin. The patients without intraamniotic inflammation (n=11) were treated expectantly. In total, 25 patients delivered 7 days after admission. All patients with intraamniotic inflammation at the initial amniocentesis who delivered after 7 days underwent follow-up amniocentesis. Treatment with antibiotics decreased the interleukin-6 concentration in the amniotic fluid at follow-up amniocentesis compared with that at the initial amniocentesis in patients with intraamniotic inflammation (median [interquartile range]: 3457 pg/mL [2493-13,203] vs 19,812 pg/mL [11,973-34,518]; P=.0001). Amniotic fluid samples with Ureaplasma species DNA had a lower microbial load at the time of follow-up amniocentesis compared with the initial amniocentesis (median [interquartile range]: 1.5×105 copies DNA/mL [1.3×105-1.7×105] vs 8.0×107 copies DNA/mL [6.7×106-1.6×108]; P=.02). CONCLUSION: Antibiotic therapy was associated with reduced intraamniotic inflammation in patients with idiopathic bleeding in the second trimester complicated by intraamniotic inflammation. Moreover, antibiotic treatment has been associated with a reduction in the microbial load of Ureaplasma species DNA in the amniotic fluid.

• MeSH
• amniocentéza škodlivé účinky   MeSH
• antibakteriální látky terapeutické užití   MeSH
• chorioamnionitida * mikrobiologie   MeSH
• děložní krvácení MeSH
• DNA MeSH
• druhý trimestr těhotenství MeSH
• interleukin-6 MeSH
• lidé MeSH
• plodová voda mikrobiologie   MeSH
• předčasný odtok plodové vody * farmakoterapie   MeSH
• retrospektivní studie MeSH
• těhotenství MeSH
• Ureaplasma MeSH
• zánět komplikace   MeSH
• Check Tag
• lidé MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: Excisional treatment of cervical intraepithelial neoplasia or very early stages of cervical cancer increases the risk of preterm prelabor rupture of membranes in subsequent pregnancies. The risk increases with the length of the excised cone. The subset of cases with preterm prelabor rupture of membranes and a history of cervical excisional treatment could also be at higher risk of intraamniotic infection/inflammation. However, there is a paucity of relevant information on this subject. OBJECTIVE: This study aimed to assess the differences in the rates of intraamniotic infection/inflammation and early-onset neonatal sepsis between singleton preterm prelabor rupture of membranes pregnancies without and with a history of cervical excisional treatment, and to investigate the association between these complications of preterm prelabor rupture of membranes and the excised cone length. STUDY DESIGN: This retrospective cohort study included 770 preterm prelabor rupture of membranes pregnancies in which transabdominal amniocentesis was performed as part of standard clinical management to assess the intraamniotic environment. The maternal and perinatal medical records of all included women were reviewed to obtain information on the absence or presence of history of cervical excisional treatment and neonatal outcomes. Women whose records contained any information on history of cervical excisional treatment were contacted by phone and in writing to inform them of the study and request permission to collect relevant information from their medical records. Women were divided into 4 subgroups according to the presence of microorganisms and/or their nucleic acids (through culturing and molecular biology methods) in amniotic fluid and/or intraamniotic inflammation (through amniotic fluid interleukin-6 concentration evaluation): intraamniotic infection (presence of both), sterile intraamniotic inflammation (intraamniotic inflammation alone), microbial invasion of the amniotic cavity without inflammation (presence of microorganisms and/or their nucleic acids in amniotic fluid alone), and negative amniotic fluid for infection/inflammation (absence of both). RESULTS: A history of cervical excisional treatment was found in 10% (76/765) of the women. Of these, 82% (62/76) had a history of only 1 treatment, and information on cone length was available for 97% (60/62) of them. Women with a history of cervical excisional treatment had higher rates of intraamniotic infection (with, 25% [19/76] vs without, 12% [85/689]; adjusted odds ratio, 2.5; adjusted P=.004), microbial invasion of the amniotic cavity without inflammation (with, 25% [19/76] vs without, 11% [74/689]; adjusted odds ratio, 3.1; adjusted P<.0001), and early-onset neonatal sepsis (with, 8% [11/76] vs without, 3% [23/689]; adjusted odds ratio, 2.9; adjusted P=.02) compared with those without such history. Quartiles of cone length (range: 3-32 mm) were used to categorize the women into 4 quartile subgroups (first: 3-8 mm; second: 9-12 mm; third: 13-17 mm; and fourth: 18-32 mm). Cone length of ≥18 mm was associated with higher rates of intraamniotic infection (with, 29% [5/15] vs without, 12% [85/689]; adjusted odds ratio, 3.0; adjusted P=.05), microbial invasion of the amniotic cavity without inflammation (with, 40% [6/15] vs without, 11% [74/689]; adjusted odds ratio, 6.1; adjusted P=.003), and early-onset neonatal sepsis (with, 20% [3/15] vs without, 3% [23/689]; adjusted odds ratio, 5.7; adjusted P=.02). CONCLUSION: History of cervical excisional treatment increases risks of intraamniotic infection, microbial invasion of the amniotic cavity without inflammation, and development of early-onset neonatal sepsis in a subsequent pregnancy complicated by preterm prelabor rupture of membranes.

• MeSH
• chorioamnionitida * epidemiologie   etiologie   MeSH
• lidé MeSH
• novorozenec MeSH
• novorozenecká sepse * MeSH
• plodová voda MeSH
• předčasný odtok plodové vody * epidemiologie   MeSH
• retrospektivní studie MeSH
• těhotenství MeSH
• zánět komplikace   MeSH
• Check Tag
• lidé MeSH
• novorozenec MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: Fertility-sparing treatment in patients with cervical cancer should, in principle, follow identical algorithms to that in patients without future reproductive plans. In recent years, a trend toward nonradical procedures, such as conization or simple trachelectomy, has become apparent in medical literature, because of their associations with better pregnancy outcomes. However, the published reports included small numbers of patients and heterogenous treatment strategies to ascertain the safety of such approaches. OBJECTIVE: This study aimed to collect multi-institutional data regarding the oncological outcomes after fertility-sparing treatment in patients with cervical cancer and to identify prognostic risk factors, including the influence of the radicality of individual cervical procedures. STUDY DESIGN: Patients aged 18 to 40 years with International Federation of Gynecology and Obstetrics 2018 stage IA1 with positive lymphovascular space invasion or ≥IA2 cervical cancer who underwent any type of fertility-sparing procedure were eligible for this retrospective observational study, regardless of their histotype, tumor grade, and history of neoadjuvant chemotherapy. Associations between disease- and treatment-related characteristics with the risk of recurrence were analyzed. RESULTS: A total of 733 patients from 44 institutions across 13 countries were included in this study. Almost half of the patients had stage IB1 cervical cancer (49%), and two-thirds of patients were nulliparous (66%). After a median follow-up of 72 months, 51 patients (7%) experienced recurrence, of whom 19 (2.6%) died because of the disease. The most common sites of recurrence were the cervix (53%) and pelvic nodes (22%). The risk of recurrence was 3 times higher in patients with tumors >2 cm in size than in patients with smaller tumors, irrespective of the treatment radicality (19.4% vs 5.7%; hazard ratio, 2.982; 95% confidence interval, 1.383-6.431; P=.005). The recurrence risk in patients with tumors ≤2 cm in size did not differ between patients who underwent radical trachelectomy and patients who underwent nonradical (conization and simple trachelectomy) cervical procedures (P=.957), regardless of tumor size subcategory (<1 or 1-2 cm) or lymphovascular space invasion. CONCLUSION: Nonradical fertility-sparing cervical procedures were not associated with an increased risk of recurrence compared with radical procedures in patients with tumors ≤2 cm in size in this large, multicenter retrospective study. The risk of recurrence after any type of fertility-sparing procedure was significantly greater in patients with tumors >2 cm in size.

• MeSH
• cervix uteri chirurgie   patologie   MeSH
• lidé MeSH
• nádory děložního čípku * chirurgie   patologie   MeSH
• retrospektivní studie MeSH
• rizikové faktory MeSH
• staging nádorů MeSH
• těhotenství MeSH
• výsledek těhotenství MeSH
• zachování plodnosti * metody   MeSH
• Check Tag
• lidé MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• pozorovací studie MeSH
• práce podpořená grantem MeSH

BACKGROUND: International guidelines recommend tailoring the radicality of hysterectomy according to the known preoperative tumor characteristics in patients with early-stage cervical cancer. OBJECTIVE: This study aimed to assess whether increased radicality had an effect on 5-year disease-free survival in patients with early-stage cervical cancer undergoing radical hysterectomy. The secondary aims were 5-year overall survival and pattern of recurrence. STUDY DESIGN: This was an international, multicenter, retrospective study from the Surveillance in Cervical CANcer (SCCAN) collaborative cohort. Patients with the International Federation of Gynecology and Obstetrics 2009 stage IB1 and IIA1 who underwent open type B/C1/C2 radical hysterectomy according to Querleu-Morrow classification between January 2007 and December 2016, who did not undergo neoadjuvant chemotherapy and who had negative lymph nodes and free surgical margins at final histology, were included. Descriptive statistics and survival analyses were performed. Patients were stratified according to pathologic tumor diameter. Propensity score match analysis was performed to balance baseline characteristics in patients undergoing nerve-sparing and non-nerve-sparing radical hysterectomy. RESULTS: A total of 1257 patients were included. Of note, 883 patients (70.2%) underwent nerve-sparing radical hysterectomy, and 374 patients (29.8%) underwent non-nerve-sparing radical hysterectomy. Baseline differences between the study groups were found for tumor stage and diameter (higher use of non-nerve-sparing radical hysterectomy for tumors >2 cm or with vaginal involvement; P<.0001). The use of adjuvant therapy in patients undergoing nerve-sparing and non-nerve-sparing radical hysterectomy was 27.3% vs 28.6%, respectively (P=.63). Five-year disease-free survival in patients undergoing nerve-sparing vs non-nerve-sparing radical hysterectomy was 90.1% (95% confidence interval, 87.9-92.2) vs 93.8% (95% confidence interval, 91.1-96.5), respectively (P=.047). Non-nerve-sparing radical hysterectomy was independently associated with better disease-free survival at multivariable analysis performed on the entire cohort (hazard ratio, 0.50; 95% confidence interval, 0.31-0.81; P=.004). Furthermore, 5-year overall survival in patients undergoing nerve-sparing vs non-nerve-sparing radical hysterectomy was 95.7% (95% confidence interval, 94.1-97.2) vs non-nerve-sparing 96.5% (95% confidence interval, 94.3-98.7), respectively (P=.78). In patients with a tumor diameter ≤20 mm, 5-year disease-free survival was 94.7% in nerve-sparing radical hysterectomy vs 96.2% in non-nerve-sparing radical hysterectomy (P=.22). In patients with tumors between 21 and 40 mm, 5-year disease-free survival was 90.3% in non-nerve-sparing radical hysterectomy vs 83.1% in nerve-sparing radical hysterectomy (P=.016) (no significant difference in the rate of adjuvant treatment in this subgroup, P=.47). This was confirmed after propensity match score analysis (balancing the 2 study groups). The pattern of recurrence in the propensity-matched population did not demonstrate any difference (P=.70). CONCLUSION: For tumors ≤20 mm, no survival difference was found with more radical hysterectomy. For tumors between 21 and 40 mm, a more radical hysterectomy was associated with improved 5-year disease-free survival. No difference in the pattern of recurrence according to the extent of radicality was observed. Non-nerve-sparing radical hysterectomy was associated with better 5-year disease-free survival than nerve-sparing radical hysterectomy after propensity score match analysis.

• MeSH
• hysterektomie škodlivé účinky   MeSH
• lidé MeSH
• nádory děložního čípku * patologie   MeSH
• přežití po terapii bez příznaků nemoci MeSH
• retrospektivní studie MeSH
• spinocelulární karcinom * patologie   MeSH
• staging nádorů MeSH
• těhotenství MeSH
• Check Tag
• lidé MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH

BACKGROUND: Minimally invasive radical trachelectomy has emerged as an alternative to open radical hysterectomy for patients with early-stage cervical cancer desiring future fertility. Recent data suggest worse oncologic outcomes after minimally invasive radical hysterectomy than after open radical hysterectomy in stage I cervical cancer. OBJECTIVE: We aimed to compare 4.5-year disease-free survival after open vs minimally invasive radical trachelectomy. STUDY DESIGN: This was a collaborative, international retrospective study (International Radical Trachelectomy Assessment Study) of patients treated during 2005-2017 at 18 centers in 12 countries. Eligible patients had squamous carcinoma, adenocarcinoma, or adenosquamous carcinoma; had a preoperative tumor size of ≤2 cm; and underwent open or minimally invasive (robotic or laparoscopic) radical trachelectomy with nodal assessment (pelvic lymphadenectomy and/or sentinel lymph node biopsy). The exclusion criteria included neoadjuvant chemotherapy or preoperative pelvic radiotherapy, previous lymphadenectomy or pelvic retroperitoneal surgery, pregnancy, stage IA1 disease with lymphovascular space invasion, aborted trachelectomy (conversion to radical hysterectomy), or vaginal approach. Surgical approach, indication, and adjuvant therapy regimen were at the discretion of the treating institution. A total of 715 patients were entered into the study database. However, 69 patients were excluded, leaving 646 in the analysis. Endpoints were the 4.5-year disease-free survival rate (primary), 4.5-year overall survival rate (secondary), and recurrence rate (secondary). Kaplan-Meier methods were used to estimate disease-free survival and overall survival. A post hoc weighted analysis was performed, comparing the recurrence rates between surgical approaches, with open surgery being considered as standard and minimally invasive surgery as experimental. RESULTS: Of 646 patients, 358 underwent open surgery, and 288 underwent minimally invasive surgery. The median (range) patient age was 32 (20-42) years for open surgery vs 31 (18-45) years for minimally invasive surgery (P=.11). Median (range) pathologic tumor size was 15 (0-31) mm for open surgery and 12 (0.8-40) mm for minimally invasive surgery (P=.33). The rates of pelvic nodal involvement were 5.3% (19 of 358 patients) for open surgery and 4.9% (14 of 288 patients) for minimally invasive surgery (P=.81). Median (range) follow-up time was 5.5 (0.20-16.70) years for open surgery and 3.1 years (0.02-11.10) years for minimally invasive surgery (P<.001). At 4.5 years, 17 of 358 patients (4.7%) with open surgery and 18 of 288 patients (6.2%) with minimally invasive surgery had recurrence (P=.40). The 4.5-year disease-free survival rates were 94.3% (95% confidence interval, 91.6-97.0) for open surgery and 91.5% (95% confidence interval, 87.6-95.6) for minimally invasive surgery (log-rank P=.37). Post hoc propensity score analysis of recurrence risk showed no difference between surgical approaches (P=.42). At 4.5 years, there were 6 disease-related deaths (open surgery, 3; minimally invasive surgery, 3) (log-rank P=.49). The 4.5-year overall survival rates were 99.2% (95% confidence interval, 97.6-99.7) for open surgery and 99.0% (95% confidence interval, 79.0-99.8) for minimally invasive surgery. CONCLUSION: The 4.5-year disease-free survival rates did not differ between open radical trachelectomy and minimally invasive radical trachelectomy. However, recurrence rates in each group were low. Ongoing prospective studies of conservative management of early-stage cervical cancer may help guide future management.

• MeSH
• adenokarcinom mortalita   chirurgie   MeSH
• adenoskvamózní karcinom mortalita   chirurgie   MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• miniinvazivní chirurgické výkony MeSH
• mladiství MeSH
• mladý dospělý MeSH
• nádory děložního čípku mortalita   chirurgie   MeSH
• přežití po terapii bez příznaků nemoci MeSH
• spinocelulární karcinom mortalita   chirurgie   MeSH
• trachelektomie MeSH
• zachování plodnosti MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Research Support, N.I.H., Extramural MeSH
• Geografické názvy
• Brazílie MeSH

• MeSH
• gestační diabetes * farmakoterapie   epidemiologie   MeSH
• hypoglykemie * chemicky indukované   epidemiologie   MeSH
• hypoglykemika škodlivé účinky   MeSH
• lidé MeSH
• metformin * škodlivé účinky   MeSH
• těhotenství MeSH
• Check Tag
• lidé MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• dopisy MeSH
• komentáře MeSH
• práce podpořená grantem MeSH

BACKGROUND: Approximately 20% of women with endometrial cancer have advanced-stage disease or suffer from a recurrence. For these women, prognosis is poor, and palliative treatment options include hormonal therapy and chemotherapy. Lack of predictive biomarkers and suboptimal use of existing markers for response to hormonal therapy have resulted in overall limited efficacy. OBJECTIVE: This study aimed to improve the efficacy of hormonal therapy by relating immunohistochemical expression of estrogen and progesterone receptors and estrogen receptor pathway activity scores to response to hormonal therapy. STUDY DESIGN: Patients with advanced or recurrent endometrial cancer and available biopsies taken before the start of hormonal therapy were identified in 16 centers within the European Network for Individualized Treatment in Endometrial Cancer and the Dutch Gynecologic Oncology Group. Tumor tissue was analyzed for estrogen and progesterone receptor expressions and estrogen receptor pathway activity using a quantitative polymerase chain reaction-based messenger RNA model to measure the activity of estrogen receptor-related target genes in tumor RNA. The primary endpoint was response rate defined as complete and partial response using the Response Evaluation Criteria in Solid Tumors. The secondary endpoints were clinical benefit rate and progression-free survival. RESULTS: Pretreatment biopsies with sufficient endometrial cancer tissue and complete response evaluation were available in 81 of 105 eligible cases. Here, 22 of 81 patients (27.2%) with a response had estrogen and progesterone receptor expressions of >50%, resulting in a response rate of 32.3% (95% confidence interval, 20.9-43.7) for an estrogen receptor expression of >50% and 50.0% (95% confidence interval, 35.2-64.8) for a progesterone receptor expression of >50%. Clinical benefit rate was 56.9% for an estrogen receptor expression of >50% (95% confidence interval, 44.9-68.9) and 75.0% (95% confidence interval, 62.2-87.8) for a progesterone receptor expression of >50%. The application of the estrogen receptor pathway test to cases with a progesterone receptor expression of >50% resulted in a response rate of 57.6% (95% confidence interval, 42.1-73.1). After 2 years of follow-up, 34.3% of cases (95% confidence interval, 20-48) with a progesterone receptor expression of >50% and 35.8% of cases (95% confidence interval, 20-52) with an estrogen receptor pathway activity score of >15 had not progressed. CONCLUSION: The prediction of response to hormonal treatment in endometrial cancer improves substantially with a 50% cutoff level for progesterone receptor immunohistochemical expression and by applying a sequential test algorithm using progesterone receptor immunohistochemical expression and estrogen receptor pathway activity scores. However, results need to be validated in the prospective Prediction of Response to Hormonal Therapy in Advanced and Recurrent Endometrial Cancer (PROMOTE) study.

• MeSH
• alfa receptor estrogenů metabolismus   MeSH
• antagonisté estrogenu terapeutické užití   MeSH
• antitumorózní látky hormonální terapeutické užití   MeSH
• doba přežití bez progrese choroby MeSH
• endometroidní karcinom farmakoterapie   genetika   metabolismus   patologie   MeSH
• imunohistochemie MeSH
• inhibitory aromatasy terapeutické užití   MeSH
• kritéria léčebné odpovědi MeSH
• lidé středního věku MeSH
• lidé MeSH
• lokální recidiva nádoru farmakoterapie   genetika   metabolismus   patologie   MeSH
• messenger RNA metabolismus   MeSH
• nádorové biomarkery metabolismus   MeSH
• nádory endometria farmakoterapie   genetika   metabolismus   patologie   MeSH
• progestiny terapeutické užití   MeSH
• receptory progesteronu metabolismus   MeSH
• regulace genové exprese u nádorů genetika   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• tamoxifen terapeutické užití   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: Ovarian cancer risk in BRCA1 and BRCA2 mutation carriers has been shown to decrease with longer duration of oral contraceptive use. Although the effects of using oral contraceptives in the general population are well established (approximately 50% risk reduction in ovarian cancer), the estimated risk reduction in mutation carriers is much less precise because of potential bias and small sample sizes. In addition, only a few studies on oral contraceptive use have examined the associations of duration of use, time since last use, starting age, and calendar year of start with risk of ovarian cancer. OBJECTIVE: This study aimed to investigate in more detail the associations of various characteristics of oral contraceptive use and risk of ovarian cancer, to provide healthcare providers and carriers with better risk estimates. STUDY DESIGN: In this international retrospective study, ovarian cancer risk associations were assessed using oral contraceptives data on 3989 BRCA1 and 2445 BRCA2 mutation carriers. Age-dependent-weighted Cox regression analyses were stratified by study and birth cohort and included breast cancer diagnosis as a covariate. To minimize survival bias, analyses were left truncated at 5 years before baseline questionnaire. Separate analyses were conducted for each aspect of oral contraceptive use and in a multivariate analysis, including all these aspects. In addition, the analysis of duration of oral contraceptive use was stratified by recency of use. RESULTS: Oral contraceptives were less often used by mutation carriers who were diagnosed with ovarian cancer (ever use: 58.6% for BRCA1 and 53.5% BRCA2) than by unaffected carriers (ever use: 88.9% for BRCA1 and 80.7% for BRCA2). The median duration of use was 7 years for both BRCA1 and BRCA2 carriers who developed ovarian cancer and 9 and 8 years for unaffected BRCA1 and BRCA2 carriers with ovarian cancer, respectively. For BRCA1 mutation carriers, univariate analyses have shown that both a longer duration of oral contraceptive use and more recent oral contraceptive use were associated with a reduction in the risk of ovarian cancer. However, in multivariate analyses, including duration of use, age at first use, and time since last use, duration of oral contraceptive use proved to be the prominent protective factor (compared with <5 years: 5-9 years [hazard ratio, 0.67; 95% confidence interval, 0.40-1.12]; >10 years [hazard ratio, 0.37; 95% confidence interval, 0.19-0.73]; Ptrend=.008). The inverse association between duration of use and ovarian cancer risk persisted for more than 15 years (duration of ≥10 years; BRCA1 <15 years since last use [hazard ratio, 0.24; 95% confidence interval, 0.14-0.43]; BRCA1 >15 years since last use [hazard ratio, 0.56; 95% confidence interval, 0.18-0.59]). Univariate results for BRCA2 mutation carriers were similar but were inconclusive because of limited sample size. CONCLUSION: For BRCA1 mutation carriers, longer duration of oral contraceptive use is associated with a greater reduction in ovarian cancer risk, and the protection is long term.

• MeSH
• dospělí MeSH
• genetická predispozice k nemoci MeSH
• kohortové studie MeSH
• kontraceptiva orální aplikace a dávkování   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mutace * MeSH
• nádory vaječníků epidemiologie   genetika   prevence a kontrola   MeSH
• následné studie MeSH
• proporcionální rizikové modely MeSH
• protein BRCA1 genetika   MeSH
• protein BRCA2 genetika   MeSH
• retrospektivní studie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Evropa MeSH

BACKGROUND: Preterm prelabor rupture of the membranes (PPROM) is frequently complicated by intraamniotic inflammatory processes such as intraamniotic infection and sterile intraamniotic inflammation. Antibiotic therapy is recommended to patients with PPROM to prolong the interval between this complication and delivery (latency period), reduce the risk of clinical chorioamnionitis, and improve neonatal outcome. However, there is a lack of information regarding whether the administration of antibiotics can reduce the intensity of the intraamniotic inflammatory response or eradicate microorganisms in patients with PPROM. OBJECTIVE: The first aim of the study was to determine whether antimicrobial agents can reduce the magnitude of the intraamniotic inflammatory response in patients with PPROM by assessing the concentrations of interleukin-6 in amniotic fluid before and after antibiotic treatment. The second aim was to determine whether treatment with intravenous clarithromycin changes the microbial load of Ureaplasma spp DNA in amniotic fluid. STUDY DESIGN: A retrospective cohort study included patients who had (1) a singleton gestation, (2) PPROM between 24+0 and 33+6 weeks, (3) a transabdominal amniocentesis at the time of admission, and (4) intravenous antibiotic treatment (clarithromycin for patients with intraamniotic inflammation and benzylpenicillin/clindamycin in the cases of allergy in patients without intraamniotic inflammation) for 7 days. Follow-up amniocenteses (7th day after admission) were performed in the subset of patients with a latency period lasting longer than 7 days. Concentrations of interleukin-6 were measured in the samples of amniotic fluid with a bedside test, and the presence of microbial invasion of the amniotic cavity was assessed with culture and molecular microbiological methods. Intraamniotic inflammation was defined as a bedside interleukin-6 concentration ≥745 pg/mL in the samples of amniotic fluid. Intraamniotic infection was defined as the presence of both microbial invasion of the amniotic cavity and intraamniotic inflammation; sterile intraamniotic inflammation was defined as the presence of intraamniotic inflammation without microbial invasion of the amniotic cavity. RESULTS: A total of 270 patients with PPROM were included in this study: 207 patients delivered within 7 days and 63 patients delivered after 7 days of admission. Of the 63 patients who delivered after 7 days following the initial amniocentesis, 40 underwent a follow-up amniocentesis. Patients with intraamniotic infection (n = 7) and sterile intraamniotic inflammation (n = 7) were treated with intravenous clarithromycin. Patients without either microbial invasion of the amniotic cavity or intraamniotic inflammation (n = 26) were treated with benzylpenicillin or clindamycin. Treatment with clarithromycin decreased the interleukin-6 concentration in amniotic fluid at the follow-up amniocentesis compared to the initial amniocentesis in patients with intraamniotic infection (follow-up: median, 295 pg/mL, interquartile range [IQR], 72-673 vs initial: median, 2973 pg/mL, IQR, 1750-6296; P = .02) and in those with sterile intraamniotic inflammation (follow-up: median, 221 pg/mL, IQR 118-366 pg/mL vs initial: median, 1446 pg/mL, IQR, 1300-2941; P = .02). Samples of amniotic fluid with Ureaplasma spp DNA had a lower microbial load at the time of follow-up amniocentesis compared to the initial amniocentesis (follow-up: median, 1.8 × 104 copies DNA/mL, 2.9 × 104 to 6.7 × 108 vs initial: median, 4.7 × 107 copies DNA/mL, interquartile range, 2.9 × 103 to 3.6 × 107; P = .03). CONCLUSION: Intravenous therapy with clarithromycin was associated with a reduction in the intensity of the intraamniotic inflammatory response in patients with PPROM with either intraamniotic infection or sterile intraamniotic inflammation. Moreover, treatment with clarithromycin was related to a reduction in the load of Ureaplasma spp DNA in the amniotic fluid of patients with PPROM <34 weeks of gestation.

• MeSH
• antibakteriální látky terapeutické užití   MeSH
• bakteriální infekce etiologie   prevence a kontrola   MeSH
• chorioamnionitida etiologie   prevence a kontrola   MeSH
• DNA bakterií analýza   MeSH
• dospělí MeSH
• interleukin-6 analýza   MeSH
• klarithromycin terapeutické užití   MeSH
• klindamycin terapeutické užití   MeSH
• kohortové studie MeSH
• lidé MeSH
• penicilin G terapeutické užití   MeSH
• plodová voda chemie   MeSH
• předčasný odtok plodové vody * MeSH
• retrospektivní studie MeSH
• těhotenství MeSH
• Ureaplasma genetika   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Research Support, N.I.H., Extramural MeSH