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Supplementary Figure from Variant Identification in BARD1, PRDM9, RCC1, and RECQL in Patients with Ovarian Cancer by Targeted Next-generation Sequencing of DNA Pools

Supplementary Table from Variant Identification in BARD1, PRDM9, RCC1, and RECQL in Patients with Ovarian Cancer by Targeted Next-generation Sequencing of DNA Pools

Several ovarian cancer susceptibility genes have been discovered, but more are likely to exist. In this study, we aimed to analyze knowledge-based selected genes, that is, BARD1, PRDM9, RCC1, and RECQL, in which pathogenic germline variants have been reported in patients with breast and/or ovarian cancer. As deep sequencing of DNA samples remains costly, targeted next-generation sequencing of DNA pools was utilized to screen the exons of BARD1, PRDM9, RCC1, and RECQL in approximately 400 Polish ovarian cancer cases. A total of 25 pools of 16 samples (including several duplicated samples with known variants) were sequenced on the NovaSeq6000 and analyzed with SureCall (Agilent) application. The set of variants was filtrated to exclude spurious variants, and, subsequently, the identified rare genetic variants were validated using Sanger sequencing. No pathogenic mutation was found within the analyzed cohort of patients with ovarian cancer. Validation genotyping of filtered rare silent and missense variants revealed that the majority of them were true alterations, especially those with a higher mutation quality value. The high concordance (R2 = 0.95) of population allele frequency for 44 common SNPs in the European control population (gnomAD) and our experiment confirmed the reliability of pooled sequencing. Mutations in BARD1, PRDM9, RCC1, and RECQL do not contribute substantially to the risk of ovarian cancer. Pooled DNA sequencing is a cost-effective and reliable method for the initial screening of candidate genes; however, it still requires validation of identified rare variants.Prevention Relevance:BARD1, PRDM9, RCC1, and RECQL are not high/moderate-risk ovarian cancer susceptibility genes. Pooled sequencing is a reliable and cost-effective method to detect rare variants in candidate genes.

Complicated or unusual cases appear in clinical practice. It's important to know how to react when we face clinical difficulty. The more unusual the case, the longer or more demanding the decision-making process is. In this case we present a patient with a gigantic ovarian tumor whose diagnosis was overturned, and the choice of the surgical procedure changed, which makes this case a very educative example of why we should consult our patients, whenever we may encounter doubts or difficulties in a therapeutic process.

Objectives: Sentinel lymph node detection (SLND) has not yet displaced lymphadenectomy, but it is a desired supplementary technique in cervical cancer surgery. The aim of our study was to identify the sources of SLND failure while performing the procedure by injecting blue dye (BD) into the cervix in cases of early-stage cervical cancer (ECC). Material and methods: We analyzed 27 consecutive ECC patients (FIGO IA2–IB1) who underwent hysterectomy with SLND and systematic lymphadenectomy between October 2011 and June 2014. The main inclusion criterion was at least unilateral SLND by BD. Predictors of either unilateral or bilateral staining were identified using multinomial logit models and a decision tree. Results: Overall, bilateral staining was achieved in nine patients (33%). Among the factors analyzed, BMI > 23.5 kg/m2 was the only factor negatively affecting the quality of SLND using BD (p < 0.02) in the univariable multinomial logit model. All patients with BMI < 23.5 kg/m2 and depth of invasion ≥ 15 mm had unilateral mapping. Conclusions: Both obese and overweight patients are unlikely to achieve optimal SLN staining with BD alone. Although some possible reasons are discussed, we believe that further studies are needed to clarify the specific limitations of other dyes currently in use.

Introduction and hypothesis The aims were to review the literature from the last two decades and analyze treatment efficacy and findings of the studies on colpocleisis. Methods A systematic search was conducted within the MEDLINE/PubMed and ClinicalTrials.gov databases, using the following keywords: pelvic organ prolapse (POP), colpocleisis, obliterative, and LeFort. All English full-text prospective and retrospective observational and interventional studies were included. Anatomical and subjective success, surgical techniques, concomitant procedures, complication rates, anesthesia methods, and decision regret were analyzed. Results A total of 237 papers were identified and 49 met the inclusion criteria. Mean patient age was 69.0 ± 8.0 to 84 ± 3.1. Over 90.2% of patients undergoing colpocleisis were diagnosed with POP stage ≥ 3. The follow-up ranged from 30 days to a median of 5 years. Anatomical success, defined as POP-Q stage ≤ 1 and no prolapse beyond the hymen, was achieved in 62.5 to 100% and 87.5 to 100% of all patients respectively. Subjective success ranged from 88% to 100%. Regret over the loss of coital ability ranged from 0% in many studies to 12.9%, general decision regret from 0% to 13.8%. After concomitant midurethral sling surgery, 86.8% to 94% of all patients were continent, with a 0–14% sling revision rate due to urinary retention. Urinary tract infection was the most common postoperative complication (4.3 to 9% confirmed with urine culture, 34.7% based on symptom definition). Bowel (0 to 2.7%) and urinary tract (0 to 9.1%) injuries were the consequences of concomitant procedures. The mortality rates were up to 1.3%. Conclusions Colpocleisis is a heterogeneous procedure, characterized by high subjective and objective success, low coital ability regret, and a low risk of complications.

A 58-year-old female ovarian cancer patient was admitted to a gynecological surgery unit from a gynecological chemotherapy unit because of right lower limb vein thrombosis. During hospitalization the patient reported a major breast enlargement occurring within a few days and mentioned a breast injury occurring a month earlier. Ultrasound performed by gyne-sonologist as well as mammography and magnetic resonance imaging examinations of the left breast revealed suspected lesion. Core-needle biopsy was performed. The histopathology examination confirmed ovarian cancer to breast metastasis. Patient died due to lymphangitis carcinomatosa as the cause of respiratory failure. The case illustrates the possible sequence of ovarian cancer development ending with breast metastasis that occurs in 0.03-0.6% of all breast cancer patients.

Background: Myometrial invasion (MI) is a parameter currently used in transvaginal ultrasound (TVS) in endometrial cancer (EC) to determine local staging, however, without molecular diagnostics, it is insufficient for selection of high-risk cases, i.e., those with a high risk of lymph node metastases (LNM). Methods: One hundred sixteen consecutive EC patients, who had received 2D transvaginal ultrasound examinations in their preoperative workup and final histopathology results as a reference standard, were included in this prospective study. Univariate and multivariate logistic models of analyzed TVS biomarkers (tumor [T] size, T area [AREA], T volume [SPE-VOL], MI, T-free distance to serosa [TFD], endo-myometrial irregularity, [EMIR], cervical stromal involvement, CSI) were evaluated to assess the relative accuracy of the possible LNM predictors. To avoid a potential bias in assuming linear relations between LNM and continuous predictors, spline functions were applied. Calculations were made in R with the use of libraries splines, glmulti, and pROC. Results: LNM was found in 20 out of 116 (17%) patients. In univariate analysis, only uMI, EMIR, uCSI and uTFD were significant predictors of LNM. Accuracy was 0.707 (AUC 0.684, 95% CI 0.568-0.801) for uMI (p50%, and SPE-VOL for patients with uCSI, allows for the most accurate prediction of LNM in EC, rather than uMI alone.

Hemoptysis in pregnancy is a very rare finding causing diagnostic and therapeutic difficulties. The case report of hemoptysis by a 29 years old patient in the 31st week of pregnancy is presented and discussed along with the diagnostic process and treatment provided.Upon pharyngeal cancer occurrence in a pregnant patient a multidisciplinary medical team performed appropriate treatment along with delivery of a healthy newborn at term. Patients and fetal conditions and outcomes were analyzed and compared to available literature in this newly created literature review.After MEDLINE database analysis using formula "hemoptysis" AND "pregnancy" more than 125 results were found published during the period 2002-2022. Almost 30 papers about hemoptysis were found and included for full analysis.The literature review offers a detailed description of previously reported incidents of hemoptysis in pregnancy to gain understanding of the etiology, differential diagnosis, available treatment and predicted future outcomes for both patient and fetus.

The aim of this study was to develop a Polish language version of the short form of the Pelvic Floor Impact Questionnaire 7 (PFIQ-7) and to validate it in a sample of Polish-speaking women with pelvic floor disorders (PFDs). The PFIQ-7 was initially translated in a stepwise fashion as guided by the International Urogynecological Association (IUGA) Translation Protocol. First, two bilingual physicians in Poland and the USA performed a forward translation of the PFIQ-7. Next, a community review process was undertaken consisting of one-on-one cognitive interviews with 20 patients. The translated questionnaire was then back translated into English. The final Polish version of the PFIQ-7 was subsequently administered to Polish-speaking patients presenting with PFDs at university-based urogynecology clinics in Poland and the USA along with a Polish version of the Pelvic Floor Distress Inventory (PFDI-20). Internal consistency and criterion validity were assessed. A total of 225 women with PFDs enrolled in this multicenter study. Complete data from 185 women in Poland and 40 primarily Polish-speaking women in the USA were analyzed. Participants had a mean age of 60.1 ± 11.1 years and mean body mass index (BMI) 27.9 ± 4.9. The Poland and United States cohorts did not vary significantly in age, BMI, or education level. PFIQ-7 internal consistency as measured by Cronbach’s alpha was good (0.93). Criterion validity was adequate between responses on the PFIQ-7 and PFDI-20 prolapse, colorectal, and urinary subscales (0.62-0.69, p

Surgical treatment of patients with peritoneal metastases in combination with Hyperthermic intraperitoneal Chemotherapy (HIPEC) and systemic treatments is applied with increasing frequency and, with correct patient qualification, allows for obtaining 5-year survival at a level of 32–52%. The conditions necessary for positive results of such treatment include the high experience of a given centre, its appropriate infrastructure, and appropriate patient qualification for the procedure. As a result of the debate connected with the need to evaluate treatment quality and results, at the request of the Peritoneal Cancer Section of the Polish Society of Oncological Surgery, the conditions for quality assurance were worked out and a Quality Assurance Commission was set up for the centres performing cytoreductive procedures and HIPEC procedures in the treatment of primary and secondary peritoneal tumours.

Background Lower limb lymphoedema (LLL) is the most disabling adverse effect of surgical staging of pelvic lymph nodes. However, the lack of standardisation of volumetric LLL assessment hinders direct comparison between the studies and makes LLL reporting unreliable. The aim of our study is to report outcomes from a prospective trial that have implications for LLL assessment standardisation. Methods In the prospective international multicentre trial SENTIX, a group of 150 patients with stage IA1–IB2 cervical cancer treated by uterine surgery with bilateral sentinel lymph node biopsy was prospectively evaluated by objective LLL assessment, based on limb volume change (LVC) using circumferrential limb measurements and subjective patient-reported swelling. The assessments were conducted in six-month periods over 24 months post-surgery. Results Patient LVC substantially fluctuated in both positive and negative directions, which were comparable in frequency up to ±14% change. Thirty-eight patients experienced persistent LVC increase >10% classified as LLL, with nine months median time to onset. Some 34.2% of cases experienced onset later than one year after the surgery. Thirty-three patients (22%) experienced transient oedema characterised as LVC >10%, which resolved without intervention between two consequent follow-up visits. No significant correlation between LVC >10% and a patient-reported swelling was observed. Conclusions Given that we observed comparable fluctuations of the the lower-limb volumes after surgical treatment of cervical cancer in both positive and negative direction up to ±14%, the diagnostic threshold for LLL diagnosis based on LVC should be increased to >15% LVC. The distinction of transient oedema from persistent LLL requires repeated measurements. Also, as one-third of LLL cases are diagnosed >1-year post-surgery, a sufficient follow-up duration needs to be ensured. Patient-reported swelling correlated poorly with LVC and should only be used as an adjunct to objective LLL assessment. Trial registration: ClinicalTrials.gov : NCT02494063

Apical defect is a pelvic organ prolapse disorder, with 5%-15% prevalence. The aim of the study was to investigate methods of laparoscopic repair of apical defect and compare them with other techniques (open, vaginal, and robotic).A systematic search of the literature was conducted in MEDLINE/PubMed and ClinicalTrials.gov databases using the following key words: apical prolapse and treatment procedures. The search was limited by using the humans filters. Only articles published in English between 2010 and 2018 were considered. Two independent authors reviewed the publications for inclusion on the basis of the following criteria: (a) use of laparoscopic techniques, and (b) apical support loss as indication for surgery.A total of 1002 papers were initially identified; 24 studies fulfilled the inclusion criteria. Four main laparoscopic procedures were found. The reported anatomical success rate (POP-Q II stage) was 77%-100%, with patient satisfaction for pectopexy, laparoscopic sacropexy (LS), lateral ligament suspension and laparoscopic uterosacral ligament suspension (LUSLS) of 96.4%-97.6%, 71.0%-100%, 66.7%-87.8%, and 95%-95.5%, respectively. Major complications included hemorrhage, bladder, ureter, and/or bowel injuries were rare. Prolapse recurrences after LUSLS and LS were reported in 13.2% and 10.4% of patients, respectively; with reoperation rate for LS 2.2%-12.8%.Most studies reported anatomical and subjective outcomes, with follow-up ranging from 1 month to7 years. Success rates for laparoscopic and abdominal corrections of apical defect were similar; laparoscopy was superior in terms of perioperative blood loss, length of hospital stay, and recovery.

AIMS To investigate relationships between pelvic floor muscles (PFM) and sexual function (SF) in sexually active (SA) and not-SA (NSA) women with pelvic floor disorders (PFD). METHODS In 350 women with PFD: 173 (49.4%) SA, 177 (50.6%) NSA, Pelvic Organ Prolapse (POP)-Quantification, PFM tone, and strength were evaluated. Transperineal ultrasound (TPS) measured genital hiatus (GH) diameter, bladder neck (BN) movement. Pelvic Organ Prolapse/Incontinence Sexual Questionnaire, IUGA-Revised (PISQ-IR), and Female Sexual Function Index (FSFI) were used. SA women were dichotomized according to muscle strength (weak/strong) and tone (normal/hypoactive). RESULTS FSFI scores reflected sexual dysfunction in 63.5% SA women. 32.2% partnered NSA stated PFD the reason for sexual inactivity. NSA women had higher POP stages and hypoactive PFM rates compared to SA: 72 (40.7%) vs 52 (30.1%), P = .04. TPS GH diameter did not differ between SA and NSA at rest, contraction, and did not correlate with SF. BN length was longer in SA at rest (15.0 ± 7.0 vs 13.1 ± 9.4, P = .03) and contraction (19.7 ± 7.0 vs 16.7 ± 10.2, P = .006); 30 (8.6%) subjects depressed BN during contraction. GH change at contraction correlated with Oxford Grading Scale (rps = 0.41; P

Cervical uterine cancer is the second most frequent female cancer worldwide and a substantial burden for low-income societies and the patients themselves. Understanding the molecular mechanisms of metastasis permits the development of therapies that limit tumor progression, as well as providing health and social benefits. Pathomorphology is still the basis of research and a reference standard for molecular analysis. The aim of our study was to research and critically evaluate clinical trials that use new oncological approaches for node-positive cervical cancer to gain an insight into the molecular mechanisms of tumor metastasis. Inclusion criteria: node-positive disease at baseline; at least a first phase clinical study comprising adult female patients; novel clinical approach (e.g., radiotherapy, immunotherapy, targeted therapy, vaccines, radiosurgery); histologic measurement of treatment efficacy (preferably lymph node ultrastaging); and publications in English language only. Information sources: US Clinical trials registry, EU Clinical trials register, ISRCTN registry, and Ovid, EBSCO and Cochrane Collaboration databases. Access dates: from January 2010 to April 2018. Exclusions: Abstracts that did not meet the inclusion criteria or with unreliable data. We collected complete data (e.g., the entire publication associated with included abstracts, heterogeneity examination of individual studies, and validity measurement of the statistical methods used). Results were analyzed in relation to the most recent understanding of the pathogenesis of cervical cancer metastasis. We proposed a possible direction for drug treatment of epithelial tumors based on the mechanisms of metastasis.

StreszczenieTransplantacja komórek krwiotwórczych (hematopoietic cell transplantation – HCT ) jest ugruntowaną metodą leczenia zarówno nienowotworowych, jak i rozrostowych chorób układu krwiotwórczego. U kobiet wiąże się jednak z występowaniem powikłań wczesnych i późnych dotyczących układu moczowo-płciowego. Konsekwencją gonadotoksycznego postępowania przygotowawczego (chemioterapii i radioterapii) jest przedwczesne wygaśnięcie funkcji jajników. U biorczyń allogenicznych przeszczepów (allogeneic HCT, allo-HCT) dodatkowo występują powikłania związane z występowaniem przewlekłej choroby przeczep przeciw gospodarzowi (chronic graft-versus-host disease – cGvHD) w istotny sposób upośledzające jakość życia kobiet w przypadku zajęcia strefy anogenitalnej (GvHDgyn). Dodatkowo przewlekła immunosupresja sprzyja występowaniu wtórnych nowotworów układu moczowo-płciowego. Pacjentki po HCT, szczególnie obciążone cGvHD, wymagają długoletniej interdyscyplinarnej opieki, włączając opiekę ginekologiczną. W pracy przedstawiono problemy ginekologiczne pacjentek po HCT oraz zaproponowano schemat standardu opieki ginekologicznej po transplantacji na podstawie piśmiennictwa i własnych doświadczeń.

Several ovarian cancer susceptibility genes have been discovered, but more are likely to exist. In this study, we aimed to analyze knowledge-based selected genes, that is, BARD1, PRDM9, RCC1, and RECQL, in which pathogenic germline variants have been reported in patients with breast and/or ovarian cancer. As deep sequencing of DNA samples remains costly, targeted next-generation sequencing of DNA pools was utilized to screen the exons of BARD1, PRDM9, RCC1, and RECQL in approximately 400 Polish ovarian cancer cases. A total of 25 pools of 16 samples (including several duplicated samples with known variants) were sequenced on the NovaSeq6000 and analyzed with SureCall (Agilent) application. The set of variants was filtrated to exclude spurious variants, and, subsequently, the identified rare genetic variants were validated using Sanger sequencing. No pathogenic mutation was found within the analyzed cohort of patients with ovarian cancer. Validation genotyping of filtered rare silent and missense variants revealed that the majority of them were true alterations, especially those with a higher mutation quality value. The high concordance (R2 = 0.95) of population allele frequency for 44 common SNPs in the European control population (gnomAD) and our experiment confirmed the reliability of pooled sequencing. Mutations in BARD1, PRDM9, RCC1, and RECQL do not contribute substantially to the risk of ovarian cancer. Pooled DNA sequencing is a cost-effective and reliable method for the initial screening of candidate genes; however, it still requires validation of identified rare variants. Prevention Relevance: BARD1, PRDM9, RCC1, and RECQL are not high/moderate-risk ovarian cancer susceptibility genes. Pooled sequencing is a reliable and cost-effective method to detect rare variants in candidate genes.

The study aimed to examine the learning curve and perioperative complications for laparoscopic pectopexy (LP). A total of 60 women with stage II–IV apical prolapse who underwent LP were dichotomized into groups: LSH(+) with concomitant laparoscopic supracervical hysterectomy (LSH), LSH(−) after previous supracervical/total hysterectomy. Operative time, estimated blood loss and hospitalization length were evaluated with cumulative sum (CUSUM) analysis and the Kwiatkowski–Phillips–Schmidt–Shin (KPSS) test, separately for two surgeons (A and B). Intraoperative and perioperative complications according to the Clavien–Dindo (C–D) classification were analyzed. Mean operative time, change in hemoglobin level, and postoperative hospital stay were 143.5 ± 23.1 min—1.5 ± 0.5g/dL and 2.5 ± 0.9 days, respectively. LSH during pectopexy was associated with longer operative time (p = 0.01) but not with higher intraoperative bleeding or prolonged hospital stay. Severe complications rate was low (1.7%) with one bowel injury in LSH(−) (C–D grade IIIb). No C–D grade II, IV and V complications were found. Conversion to open pectopexy, return to the operating room or blood transfusion were not required. The KPSS test showed that a steady operative time for Surgeon A was achieved after 28 procedures. A proficiency for laparoscopic pectopexy based on CUSUM analysis was observed after 38–40 procedures.

IntroductionUterine malignancies, the vast majority of which are endometrial cancers, constitute the most common type of gynecological neoplasms in developed countries. The primary treatment for endometrial cancer is hysterectomy and bilateral salpingoophorectomy. Women with endometrial cancer can be subjected to either total abdominal hysterectomy (TAH) or to an increasingly recommended total laparoscopic hysterectomy (TLH). We decided to verify whether published evidence supports TLH as an effective, less invasive than TAH albeit still equally radical treatment for endometrial malignancies.Material and methodsThe systematic review included articles indexed in MEDLINE (PubMed) and EBSCO, published between January 1974 and January 2017. The search was based on the following keywords and combinations thereof: “laparoscopy”, “laparotomy”, “endometrial cancer”, “comparative”. Twenty-six full-text articles were included in the meta-analysis.ResultsA total of 5,996 patients were eligible for the analysis, among them 2,833 (47.2%) women subjected to TLH and 3,163 (52.8%) who underwent TAH. Total laparoscopic hysterectomy is associated with shorter hospital stay, faster recovery, lesser blood loss and fewer intra- and postoperative blood transfusions, reduced pain, and a lower reoperation rate than conventional TAH.ConclusionsAll analyzed studies demonstrated that TLH is a safe and effective treatment option in endometrial cancer patients. This procedure is markedly less invasive than TAH. However, considering several contraindications for laparoscopy, such as peritoneal invasion, cardiorespiratory failure, history of previous surgery and large size of the uterus, qualification for a given procedure needs to be preceded by a detailed evaluation.

Current oncological developments are based on improved understanding of genetics, and especially the discovery of genes whose alterations affect cell functions with consequences for the whole body. Our work is focused on the one of these genes, BRCA1-associated RING domain protein 1 (BARD1), and its oncogenic role in breast cancer. Most importantly, the study points to new avenues in the treatment and prevention of the most frequent female cancer based on BARD1 research. The BARD1 and BRCA1 (BReast CAncer type 1) proteins have similar structures and functions, and they combine to form the new molecule BARD1-BRCA1 heterodimer. The BARD1-BRCA1 complex is involved in genetic stabilization at the cellular level. It allows to mark abnormal DNA fragments by attaching ubiquitin to them. In addition, it blocks (by ubiquitination of RNA polymerase II) the transcription of damaged DNA. Ubiquitination, as well as stabilizing chromatin, or regulating the number of centrosomes, confirms the protective cooperation of BARD1 and BRCA1 in the stabilization of the genome. The overexpression of the oncogenic isoforms BARD1β and BARD1δ permit cancer development. The introduction of routine tests, for instance, to identify the presence of the BARD1β isoform, would make it possible to detect patients at high risk of developing cancer. On the other hand, introducing BARD1δ isoform blocking therapy, which would reduce estrogen sensitivity, may be a new line of cancer therapy with potential to modulate responses to existing treatments. It is possible that the BARD 1 gene offers new hope for improving breast cancer therapy.

The aim of this study was to develop a Polish language version of the short form of the Pelvic Floor Impact Questionnaire 7 (PFIQ-7) and to validate it in a sample of Polish-speaking women with pelvic floor disorders (PFDs).The PFIQ-7 was initially translated in a stepwise fashion as guided by the International Urogynecological Association (IUGA) Translation Protocol. First, two bilingual physicians in Poland and the USA performed a forward translation of the PFIQ-7. Next, a community review process was undertaken consisting of one-on-one cognitive interviews with 20 patients. The translated questionnaire was then back translated into English. The final Polish version of the PFIQ-7 was subsequently administered to Polish-speaking patients presenting with PFDs at university-based urogynecology clinics in Poland and the USA along with a Polish version of the Pelvic Floor Distress Inventory (PFDI-20). Internal consistency and criterion validity were assessed.A total of 225 women with PFDs enrolled in this multicenter study. Complete data from 185 women in Poland and 40 primarily Polish-speaking women in the USA were analyzed. Participants had a mean age of 60.1 ± 11.1 years and mean body mass index (BMI) 27.9 ± 4.9. The Poland and United States cohorts did not vary significantly in age, BMI, or education level. PFIQ-7 internal consistency as measured by Cronbach's alpha was good (0.93). Criterion validity was adequate between responses on the PFIQ-7 and PFDI-20 prolapse, colorectal, and urinary subscales (0.62-0.69, p 0.05).The Polish version of the PFIQ-7 is a reliable tool for evaluating pelvic floor symptoms in Polish-speaking women with PFDs.

AIMS To assess responsiveness of sexual function questionnaires: Pelvic Organ Prolapse/Incontinence Sexual Questionnaire, IUGA-Revised (PISQ-IR) and Female Sexual Function Index (FSFI) in women with pelvic floor disorders (PFD). METHODS The study included 261 subjects who completed PISQ-IR and FSFI at baseline and after treatment (median: 8 months). Standardized response mean (SRM) and effect size (ES) were calculated for sexually active (SA) and not-SA (NSA) women. Patient Global Impression of Improvement (PGI-I) was applied to assess treatment outcomes. RESULTS A total of 184 women reported "very much better"/"much better" on the PGI-I scale posttreatment and were enrolled for further study. After treatment, 21.7% of the NSA women resumed sexual activity, 13.9% of the initially SA-abstained, and no change was reported for 152 (82.6%) subjects (87-SA and 65-NSA). Significant improvement in PISQ-IR SA domains was observed, with mild responsiveness for Arousal/Orgasm (SRM = 0.34, ES = 0.29, p = .003) and good responsiveness for Condition Specific, Global Quality and Summary Score (SRM = 0.51, ES = 0.50; SRM = 0.54, ES = 0.47; SRM = 0.75, ES = 0.63, p

The quality of pathological assessment is crucial for the safety of patients with cervical cancer if pelvic lymph node dissection is to be replaced by sentinel lymph node (SLN) biopsy. Central pathology review of SLN pathological ultrastaging was conducted in the prospective SENTIX/European Network of Gynaecological Oncological Trial (ENGOT)-CX2 study. All specimens from at least two patients per site were submitted for the central review. For cases with major or critical deviations, the sites were requested to submit all samples from all additional patients for second-round assessment. From the group of 300 patients, samples from 83 cases from 37 sites were reviewed in the first round. Minor, major, critical, and no deviations were identified in 28%, 19%, 14%, and 39% of cases, respectively. Samples from 26 patients were submitted for the second-round review, with only two major deviations found. In conclusion, a high rate of major or critical deviations was identified in the first round of the central pathology review (28% of samples). This reflects a substantial heterogeneity in current practice, despite trial protocol requirements. The importance of the central review conducted prospectively at the early phase of the trial is demonstrated by a substantial improvement of SLN ultrastaging quality in the second-round review. ispartof: CANCERS vol:12 issue:5 ispartof: location:Switzerland status: published

Objectives: To assess the significance of pathologic ultrastaging (PU) of sentinel (SLN) and non-sentinel (nSLN) lymph nodes (LNs) and the influence on cancer staging in patients with International Federation of Gynecology and Obstetrics (FIGO) stage IA2-IB1 cervical cancer. Material and methods: A retrospective study was conducted with 54 patients divided into two equal-sized groups. In test group (n1), at least one SLN/patient was detected with blue dye. All excised LNs in this group were subjected to PU (4 μm slices/150 μm intervals) with hematoxylin-eosin staining and immunohistochemistry (AE1-AE3 antibodies). In none of the control group (n2) was PU performed, but in 2 patients SLN concept was performed. Patients in both groups underwent radical hysterectomy and lymphadenectomy. The effect of PU was expressed in puTNM and compared with both standard pTNM and FIGO systems. The influence of PU on patients’ disease-free survival (DFS) and overall survival (OS) was assessed using Kaplan-Meier curves. Results: In total, 516 LNs were extracted (66 SLNs, 36% bilaterally). Micrometastases (MIC) or isolated tumor cells (ITC) were detected in 34 of the 482 LNs (7.1%), including 16 MICs and 9 ITC in non-SLNs. False negative rates were: 3.7%/side-specific, and 7.4%/both sides. The use of PU resulted in stage change in 2 cases (N and M status change), FIGO stage did not changed. No PU impact on DFS or OS was observed. Conclusions: The risk of TNM stage migration in early cervical cancer is low, is more likely in inattentively evaluated patients, and has indeterminate prognostic and predictive value. Selection of cases with cT ≤ 2 cm and cN0 is sufficient to avoid the risk of improper staging.

The aim of this study was to develop a Polish language version of the short form of the Pelvic Floor Distress Inventory (PFDI-20) and to validate it in a sample of Polish-speaking women with pelvic floor disorders (PFDs). The PFDI-20 was initially translated in a stepwise fashion as guided by the International Urogynecological Association (IUGA) Translation Protocol. After initial forward translation from English to Polish, a community review process consisting of cognitive interviews and confirmation via back translation was performed. The final Polish version of the PFDI-20 was administered to Polish-speaking patients presenting with PFDs at university-based urogynecology clinics in Poland and the United States, along with a Polish version of the King’s Health Questionnaire (KHQ). Internal consistency and criterion validity were assessed. Test–retest reliability was assessed in 100 patients after 2 weeks. A total of 254 women with PFDs enrolled in this multicenter study. Complete data from 44 Polish-speaking women in the United States and 200 women in Poland were analyzed. Participants had a mean age of 60.3 ± 11.2 years and mean body mass index (BMI) 27.6 ± 4.7. Internal consistency as measured by Cronbach’s alpha was good (0.89). Criterion validity was adequate between responses on the KHQ and PFDI-20 with Pearson correlations in particular domains (0.27–0.50, P

Introduction and hypothesis The aim of the study was to translate into Polish the Pelvic Organ Prolapse/Incontinence Sexual Questionnaire, IUGA-Revised (PISQ-IR), which evaluates sexual function in sexually active (SA) and not SA (NSA) women with pelvic floor disorders (PFD), and to validate the Polish version. Methods After translation, back-translation and cognitive interviews, the final version of PISQ-IR was established. The study group included 252 women with PFD (124 NSA and 128 SA). All women underwent clinical evaluation and completed the PISQ-IR. For test–retest reliability, the questionnaire was administered to 99 patients twice at an interval of 2 weeks. The analysis of criterion validity required the subjects to complete self-reported measures. Internal consistency and criterion validity were assessed separately for NSA and SA women for the PISQ-IR subscales. Results The mean age of the women was 60.9 ± 10.6 years and their mean BMI was 27.9 ± 4.9 kg/m2. Postmenopausal women constituted 82.5% of the study group. Urinary incontinence (UI) was diagnosed in 60 women (23.8%), pelvic organ prolapse (POP) in 90 (35.7%), and UI and POP in 102 (40.5%). Fecal incontinence was reported by 45 women (17.9%). The PISQ-IR Polish version proved to have good internal consistency in NSA women (α 0.651 to 0.857) and SA women (α 0.605 to 0.887), and strong reliability in all subscales (Pearson’s coefficient 0.759–0.899; p

The aim of this paper is to review and to analyze the results of previous studies dealing with hysteroscopic treatment of postcesarean scar defects. A systematic review of publications indexed in MEDLINE/PubMed database identified a total of 11 studies dealing with resectoscopic treatment of postcesarean scar defect. The review was conducted in line with the Meta-analysis of Observational Studies in Epidemiology (MOOSE) guidelines and the PRISMA statement. In only few studies, patients were qualified for hysteroscopic surgery based on the measurement of the defect depth and thickness of residual myometrium above the pouch. Two principal techniques were used for the hysteroscopic treatment: resection of one edge of the scar diverticulum, and resection of the inferior and superior edges of the defect. Additionally, most authors performed electrocauterization of the niche bottom. Resectoscopic treatment turned out to be highly effective in the case of women with AUB. No complications of the hysteroscopic procedure have been reported. Methodological value of the reviewed studies was relatively low due to non-unified selection/verification criteria and incomplete, non-systematic postoperative assessment. In conclusion, hysteroscopic treatment seems to be a promising option in the management of postcesarean scar defects, but still further research is needed on the problem in question.

BACKGROUND: Elevated serum cancer antigen 125 (CA-125) is observed in some cervical cancers (CCs). Is the correlation of CA-125 with the presence of nodal events useful in predicting early metastasis to the lymph nodes?METHODS: The study included 45 patients with CC FIGO (2009) stages IA1-IIA1 and known preoperative CA-125 concentration, surgery treated (05.2011-05.2014). Investigated pretreatment: age (pre-, postmenopausal), histological type, grade, confounding factors - prior cone biopsy, ovarian cyst, endometriosis, liver or colon pathology, concomitant malignancy. LN metastases (LNM) were defined as macro (MAC, >2mm) and/or micrometastases (mic, 0.2 - 2 mm), and LVLND as mic or/and ITC (single CC cells clusters) in LNs. Ultrastaging of all LNs (sentinel and non-sentinel, 4 μm thick slices/150 μm intervals) was performed with hematoxylin and eosin staining and with immunohistochemistry (IHC - AE1/AE3 cytokeratin antibodies). Non-parametrical analysis and receiver operating curve analysis were used to determine correlation between CA-125 and LNM including LVLND.RESULTS: The median age was 55 (23-71). 806 LNs were extracted. LNM was found in 12, LVLND in 6 patients. LNM but not LVLND was correlated with higher grade (G2-G3, pCONCLUSIONS: Elevated levels of CA-125 may be less likely due to LVLND than to LN positivity. Grade is an important feature in prediction of LNM but not LVLND. CA-125 level was found to be not predictive of LNM nor LVLND, as confirmed by ultrastaging.

In everyday gynecological practice, there is an unmet need to manage survivors after allogeneic hematopoietic cell transplantation (allo-HCT). The major gynecological complications include premature ovarian insufficiency (POI), chronic graft-versus-host disease (cGVHD) of the anogenital zone (cGVHDgyn), and secondary neoplasms. Aiming to assess a real-life scale of problems associated with HCT, we performed a detailed analysis of a consecutive series of females after allo-HCT who were referred for a routine gynecological evaluation. The study includes 38 females after allo-HCT in whom gynecological examination with cervical smear and USG were performed, followed by colposcopy according to NCCN guidelines. NIH scoring system was used to classify a grade of cGVHDgyn. The incidence of cGVHD was 71% whereas GVHDgyn was 29%, including 5 patients with score 3 at the time of diagnosis. The other manifestations (frequently noted) included the skin, mucosa, eyes, and liver. Menopause was diagnosed in 93% females, and in 81% of them, POI criteria were fulfilled. Ovarian function resumed in 2 cases. The rate of abnormal cytology was 26%: 4 ASCUS, 1 AGUS, 1 LSIL, 3 HSIL/ASC-H, and one cytological suspicion of cervical cancer. GVHDgyn was documented in 10 patients, and 6 of them had abnormal cervical cytology. Early topical estrogen therapy led to a significant reduction in vaginal dryness (p p p

Introduction/Background SENTIX is a prospective cohort multicenter international study on sentinel lymph node (SLN) biopsy without pelvic lymph node dissection (PLND) in patients with early-stage cervical cancer. SLN frozen section (FS) and pathological ultrastaging were mandatory. Samples from SLN were reviewed centrally for pathological assessment quality control. Only sites experienced in SLN biopsy technique were eligible. Methodology In total, 47 sites from 18 countries participated in the study. Patients with stages T1a1/LVSI+ - T1b2 ( Results Data from 372 patients were analyzed who were pre-registered at the time when the number of cases treated per protocol reached 300. Patient characteristics are shown in table 1. Bilateral detection rate reached 91%. table 2 shows factors influencing SLN detection. Frozen section detected macrometastases (MAC) in 22 cases. SLN ultrastaging found additional 7 cases with MAC, 19 with micrometastases (MIC) and 11 with isolated tumor cells (ITC). Sensitivity of FS was 75.9% for the detection of MAC and 37.3% for any type of SLN involvement. Conclusion High bilateral detection can be achieved in sites experienced in the SLN biopsy technique. We did not confirm a higher detection rate using ICG. FS failed to detect 26/48 (54%) of cases with MIC or MAC in SLN. Disclosure This work was supported by a grant from the Czech Research Council (No 16-31643A). Conflict of interest: None of the authors declare a conflict of interest.

Introduction/Background The laparoscopy has been found to be attractive and safe technique in gynaecological oncology. However, some recent retrospective and prospective reports on early-stage cervical cancer have shown unexpected contrary results in terms of overall and disease-free survival. In our opinion, published discussions to date do not fully address the subject and that it is worth considering important issues that were not given enough attention before. Methodology We conducted a systematic analysis of current knowledge about laparoscopy in early-stage cervical cancer by reviewing the relevant literature from the fields of basic and clinical research, starting with the results of the Laparoscopic Approach to Cervical Cancer (LACC) study, and including analysis of its appendix and protocol. Results The preferred surgical access in cervical cancer cases was the subject of a single prospective randomized clinical trial. Other, similarly designed studies on other pelvic tumours are sparse. The biology of cancer, cancer epidemiology, as well as surgical skills and details of laparoscopic techniques underlie the observed differences in survival rates. Conclusion There are some possibilities (such as limiting the manipulation of the uterus, closure of tubes and ligation of the parametria before using the manipulator, closure of the vaginal cuff, applying warmed and humidified CO2, and limiting intra-abdominal gas pressure) that, if considered and applied, may affect oncological results in selecting laparoscopy as the operative method for early-stage cervical cancer. Disclosure Nothing to disclose.

Introduction/Background The purpose of the study is to compare the two operative techniques in cervical cancer and to determine whether laparoscopy is a safe and effective alternative to conventional abdominal radical hysterectomy (RAH). Methodology Fifty-one cases of radical laparoscopic hysterectomy (RLH) and 41 cases of RAH performed in Medical University in Gdansk (Poland) between 2013–2019 were compared and analyzed in a retrospective observational study. Since the publication of prospective LACC trial in 2018 reporting incomparably worse outcomes of minimally invasive techniques in cervical cancer, laparotomy or modified procedure of vaginally assisted laparoscopic radical hysterectomy (VALRH) without uterine manipulator, was carried out in all patients. We included patients with early-stage cervical cancer only: IA1–IB1 according to FIGO 2014 staging. Results There were no differences in preoperative clinical FIGO stage in both groups, with the most common Ib1 in 93% and 86% of patients respectively in RAH and RLH group. Although squamous cell cancer was the most frequent, we found a high percentage of adenocarcinoma in RLH (25%) compared to RAH (7%), which can affect the long-term outcomes. We have shown a significantly less blood loss in the minimally invasive technique (p 0.05). There were no differences in recurrences in both groups (5.8% for RLH and 5% for RAH). Conclusion As in oncology of the 21st century, we are more and more interested in patients quality of life, we have to focus on the development of minimally invasive techniques. Radical laparoscopic hysterectomy still can be a safe and effective alternative to laparotomy in early-stage cervical cancer. Disclosure Nothing to disclose.

Introduction and hypothesis To assess the impact of coital incontinence (CI) on health-related quality of life (HRQoL) and quality of sexual function (QSF) in women with urodynamic stress urinary incontinence (SUI). Methods Women were recruited for this cross-sectional study from among 289 patients with lower urinary tract symptoms, underwent clinical and urodynamic evaluation. Of these 289 women, 127 sexually active women with SUI completed the King’s Health Questionnaire (KHQ) and the Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire (PISQ), of whom 97 were enrolled for the study. The study group comprised 53 women with CI occurring ‘sometimes’, ‘usually’ or ‘always’, and the control group comprised 44 women without CI. Total and individual domain scores were evaluated. Results CI was reported by 65.35 % of the women. The frequency of CI was correlated with lower educational level and higher body mass index (r = 0.22 and r = 0.23, respectively; p = 0.01). The KHQ results showed significantly lower HRQoL in women with CI in all domains (p

Constitutional loss-of-function pathogenic variants in the tumor suppressor genes BRCA1 and BRCA2 are widely associated with an elevated risk of ovarian cancer (OC). As only ~15% of OC individuals carry the BRCA1/2 pathogenic variants, the identification of other potential OC-susceptibility genes is of great clinical importance. Here, we established the prevalence and spectrum of the germline pathogenic variants in the BRCA1/2 and 23 other cancer-related genes in a large Polish population of 333 unselected OC cases. Approximately 21% of cases (71/333) carried the BRCA1/2 pathogenic or likely pathogenic variants, with c.5266dup (p.Gln1756Profs*74) and c.3700_3704del (p.Val1234Glnfs*8) being the most prevalent. Additionally, ~6% of women (20/333) were carriers of the pathogenic or likely pathogenic variants in other cancer-related genes, with NBN and CHEK2 reported as the most frequently mutated, accounting for 1.8% (6/333) and 1.2% (4/333) of cases, respectively. We also found ten pathogenic or likely pathogenic variants in other genes: 1/333 in APC, 1/333 in ATM, 2/333 in BLM, 1/333 in BRIP1, 1/333 in MRE11A, 2/333 in PALB2, 1/333 in RAD50, and 1/333 in RAD51C, accounting for 50% of all detected variants in moderate- and low-penetrant genes. Our findings confirmed the presence of the additional OC-associated genes in the Polish population that may improve the personalized risk assessment of these individuals.

Background Ficolin-3 is a pattern-recognition molecule with the ability to activate the lectin pathway of complement. It is found in lung, liver and blood, but its physiological role is unclear. We have investigated interaction of recombinant ficolin-3 with malignant cells and tissues. Material and Methods Cells of various lines of human origin as well as ovarian tissue sections have been studied with the use of flow cytometry and immunohistochemistry. Results Recombinant (but not serum-derived) ficolin-3 was found to bind strongly to the ovarian cancer cell lines, SKOV-3, OVCAR-3 and ES-2, at concentrations of 2.5 μg/ml and above. Moreover, His-tagged recombinant ficolin-3 (10 μg/ml) preferentially stained ovarian tissue sections from patients with malignant tumours compared with those from patients without. Binding to cell lines was inhibited by EDTA and specific carbohydrate ligands, indicating involvement of the fibrinogen-like domain. Binding was enhanced under mildly acidic conditions and at physiological pH after pre-incubation of cells with mildly acidic buffer. Conclusion Basing on data concerning recombinant protein, it may be suggested that ficolin-3 is involved in immune response in ovarian cancer. However, unidentified serum factor(s) seem(s) to protect cancer cells from recognition by natural or rficolin-3.

Niche, a newly described in the polish literature cesarean section complication, is defined as a triangular anechoic deficient of the uterine myometrium localized in the site of the scar after the incision of a typically performed low-transverse cesarean delivery. The aim of the paper is to provide an overview of the available literature on the diagnosis and symptoms of niche. Diagnostic evaluation of the niche comprises of visual diagnostic methods: transvaginal ultrasonography to localize the cesarean scar and contrast-enhanced sonography as the method of choice for measuring the depth of the niche, the residual myometrium thickness and the total myometrial thickness. The mechanisms of niche development have not yet been revealed, although, as suggested, it may be a coincidence of many factors as: closure technique, development of the lower uterine segment or location of the incision and wound healing. The symptoms related to the presence of a niche are: abnormal uterine bleeding, lower abdominal pain, infertility, urination problems and obstetrical complications which may be life-threatening for both the women and the fetus. The suggested relation between the niche and the occurrence of complications in future pregnancies, as uterine rupture and implantation of the gestational sack in the site of the diverticulum, are still unexplained.

Cel: Nierodztwo jest jednym z najwazniejszych czynnikow ryzyka rozwoju raka blony śluzowej trzonu macicy. Wciąz trwają rozwazania, czy wielorodztwo implikuje bardziej korzystny przebieg choroby i wyzsze wspolczynniki calkowitego przezycia chorych. Celem pracy jest ocena wplywu rodności na calkowite przezycie kobiet w Polsce z rakiem blony śluzowej trzonu macicy. Material i metody: Retrospektywna analiza wplywu rodności na wspolczynniki przezycia zostala przeprowadzona u 810 kobiet leczonych operacyjnie z powodu raka blony śluzowej trzonu macicy w ośrodku referencyjnym ginekologii onkologicznej. Wyniki: Wykazano, ze wyzsza rodnośc jest związana z istotnie nizszym wspolczynnikiem calkowitego przezycia chorych (p=0.03). Rodnośc okazala sie byc niezaleznym czynnikiem przezycia chorych (HR 1.9). Wielokrotne wielorodki byly starsze w chwili zabiegu operacyjnego, stwierdzano u nich cześciej glebokie naciekanie mieśniowki macicy i cześciej naciek podścieliska szyjki macicy oraz wyzsze stopnie zaawansowania nowotworu (wylącznie w klasyfikacji FIGO z 1988 roku). Grupa wielokrotnych wielorodek charakteryzowala sie znacząco nizszym wspolczynnikiem nawrotow choroby. Kobiety te statystycznie cześciej cechowalo posiadanie nizszego wyksztalcenia, cześciej rowniez stwierdzano u nich obecnośc chorob towarzyszących w tym rowniez wystepowanie innych nowotworow zlośliwych. W grupie tej jednakze rzadziej wystepowaly nowotwor piersi i jelita grubego niz u pozostalych kobiet. Wnioski: Wielorodztwo okazuje sie byc niekorzystnym czynnikiem prognostycznym przezycia u Polek. Niekorzystne rokowanie w raku blony śluzowej trzonu macicy w tej grupie jest mniej związane z nierodztwem a zdecydowanie bardziej związane z interakcją niekorzystnych czynnikow ryzyka i negatywnych czynnikow prognostycznych, ktore tworzą sprzyjające okoliczności i środowisko dla wzrostu nowotworu.

The aim of the study was to develop a Polish version of the Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire (PISQ) to evaluate sexual function in patients with stress urinary incontinence (SUI) and pelvic organ prolapse (POP) versus a control group. Before the validation study, a pilot study of the Polish version of the PISQ was performed in 22 women with pelvic floor dysfunctions. The respondents completed the questionnaire at recruitment and 2 weeks later. Test–retest reliability and internal consistency were determined. The validation study was performed in 249 sexually active women (123 with urodynamic SUI and POP; 126 healthy controls). The study group reported urinary incontinence (UI) at the urogynecological ambulatory clinic, where they underwent urogynecological and urodynamic examinations. All participants completed the questionnaire. PISQ results from both groups were compared and correlated with those of the King’s Health Questionnaire (KHQ) and patient age. Test–retest reliability was good according to Pearson’s correlation coefficient (r = 0.89, p

ObjectivesSentinel lymph node biopsy (SLNB) can identify patients with nodal metastases who are eligible for tailored treatment. The aim of study was to compare the SLN detection rates using cervical and subserosal administration of 2 tracers.ResultsIn group 1 (82 patients), SLNB was performed using radiocolloid injected to the cervix and blue dye administered to the fundus. In group 2, blue dye was injected to cervix and fundus (106 patients). Only SLNB was performed in 128 (68.1%) women. In the remaining 60 (31.9%) patients, pelvic/para-aortic lymphadenectomy together with SLNB was performed. Groups 1 and 2 did not differ with regard to the frequencies of SLNB and lymphadenectomy. The detection rate for both groups was 90.9%. Bilateral detection was achieved in 72.5%. Para-aortic SLNs were found in 9.6%. Detection rates in groups 1 and 2 were 95.1% and 87.7% (P= 0.065). In comparison of cervical administration of radioisotope and subserosal injection of blue dye in group 1, we found a significant difference for total SLN detection (91.5% vs 74.4%,P< 0.05) and no significant difference for bilateral detection (73.3% vs 59.1%,P= 0.776). We did not find differences in the para-aortic SLN detection rates achieved after administration of a radiotracer and injection of a blue dye (4.9% vs 9.8%,P= 0.184). Eighteen patients (9.6%) presented with nodal disease, including 15 women with SLN involvement. The false-negative rate, calculated for patients subjected to lymphadenectomy, was 12.5% (1/8); using the SLNB surgical algorithm, it was 10% (1/10).ConclusionsCervical administration of a tracer, especially radioisotope, results in high SLN detection rates. In turn, the subserosal injection can be used only as an adjuvant method for SLNB. Low para-aortic SLN detection rates observed after cervical administration of a tracer do not seem to be a serious limitation of this technique.