Ultrasound-guided breast-conserving surgery compared to conventional breast-conserving surgery.

PURPOSE: The goal of breast-conserving surgery is to achieve negative tumor margins, since insufficient marginal distance is associated with more local and distant recurrences. This study investigates whether IOUS (intraoperative ultrasound) can reduce the re-resection rate compared to standard breast surgery, regardless of tumor biology and focality. MATERIALS AND METHODS: The present study is a monocentric, prospective, randomized, and non-blinded parallel group study conducted between 7/2015 and 2/2018. Patients with sonographically visible breast cancer were randomized into two study arms: 1) breast-conserving surgery with IOUS; 2) conventional arm. RESULTS: 364 patients were included in the study and underwent surgery. Tumor biology, size, and focality were equally distributed in both groups (p = 0.497). The study arms did not differ significantly in the proportion of preoperative wire markings (p= 0.084), specimen weight (p = 0.225), surgery duration (p = 0.849), and the proportion of shavings taken intraoperatively (p = 0.903). Positive margins were present in 16.6% of the cases in the IOUS arm and in 20.8% in the conventional arm (p = 0.347). Re-operation was necessary after intraoperative shavings in 14.4% of cases in the US arm and in 21.3% in the conventional arm (p = 0.100). CONCLUSION: Although the present study showed a clear difference in the rate of positive tumor margins with IOUS compared to conventional breast surgery without IOUS, this was not statistically significant in contrast to the current literature. This could be due to the high expertise of the breast surgeons, the precise wire marking, or the fact that the IOUS technique was not standardized.

Fertility preserving management of early endometrial cancer in a patient cohort at the department of women's health at the university of Tuebingen.

PURPOSE: To investigate the oncologic and reproductive outcome of a conservative treatment with progestin agents in early-stage grade 1 endometrial cancer (G1EC), grade 2 endometrial cancer (G2EC) or complex atypical hyperplasia (CAH) in young premenopausal women. METHODS: Women treated for early-stage endometrial cancer or atypical hyperplasia of the endometrium with a conservative therapy between 2006 and 2018 were enrolled in this retrospective analysis. Progestin agents were orally administered on a daily basis for 3 months for at least one cycle. Endometrial tissue was obtained by hysteroscopy and Dilatation & Curettage (D&C) being performed before and after end of treatment. Therapeutic response was assessed by pathological examination. RESULTS: A total of 14 patients were included. After treatment with progestin agents, 11 of these patients initially showed a complete or partial response. Three patients with early-stage endometrial cancer did not respond. Of the three patients with initially diagnosed atypical hyperplasia, none showed any remaining disease later. Of the eight patients with initially diagnosed endometrial cancer, who had responded to first treatment, three patients were re-diagnosed with endometrial cancer later. One patient with initial endometrial cancer became pregnant but aborted in the 10th week. CONCLUSION: Due to its good efficacy, progestin agents offer a feasible therapeutic option in the fertility-preserving treatment of early-stage endometrial cancer in young premenopausal women. However, recurrence rate remains high. Therefore, a close follow-up is mandatory, also in responders. Patients should be informed of limitations and risks of conservative treatment. Yet after completion of family planning, hysterectomy should be performed.

Sustained prognostic impact of circulating tumor cell status and kinetics upon further progression of metastatic breast cancer.

PURPOSE: Serial longitudinal enumeration of circulating tumor cells (CTCs) has shown its prognostic value on progression-free survival and overall survival (OS) in patients with stage IV breast cancer. This study prospectively evaluated the role of CTCs as a prognostic marker during further progression of metastatic breast cancer (MBC). METHODS: Among 476 MBC patients recruited between 2010 and 2015, the 103 patients with a known CTC status at baseline (CTCBL) and within 4 weeks of tumor progression (CTCPD) were included. Progressive disease (PD) was defined according to the Response Evaluation Criteria in Solid Tumors (RECIST, version 1.1). Using the CellSearch method, < 5 and ≥ 5 CTCs per 7.5 ml blood were determined as negative and positive, respectively. A shift in CTC status from baseline to progression ([Formula: see text] to [Formula: see text] and vice versa) was considered as alternating KineticsBL-PD. RESULTS: Median follow-up was 29.9 [21.2, 40.0] months. CTCPD positivity (37%, n = 38) was associated with a significantly shorter OS than CTCPD negativity (8.0 [5.1, 10.9] vs 22.6 [15.3, 39.8] months; P < 0.001). Alternating KineticsBL-PD was observed in 24% of the patients. This significantly changed the OS prediction of [Formula: see text] patients ([Formula: see text] vs [Formula: see text], 11.4 [9.7, not available (NA)] vs. 7.6 [4.4, 11.5] months; P = 0.044) and [Formula: see text] patients ([Formula: see text] vs. [Formula: see text], 8.4 [4.0, NA] vs. 22.6 [18.9, NA] months, respectively; P < 0.001). Prediction of survival was significantly improved (P = 0.002) by adding CTCPD status to clinicopathological characteristics and CTCBL status. CONCLUSIONS: CTC status upon further disease progression is a prognostic factor that could significantly improve well-established models. Thus, it represents a potential additional instrument supporting treatment decision.

Female genital tract congenital malformations and the applicability of the ESHRE/ESGE classification: a systematic retrospective analysis of 920 patients.

PURPOSE: Several classification systems for female genital tract anomalies exist but are of limited use in clinical practice. We, therefore, assessed the applicability and ease of use of the new ESHRE/ESGE classification, using only patient records. METHODS: This retrospective, single-center, proof-of-principle study systematically analyzed the surgical reports and other hospital records of 920 inpatients and outpatients treated for confirmed female genital tract congenital malformations at a major German university hospital during 2003-2013. Using only this information, a non-expert (medical student) assigned patients to an ESHRE/ESGE class, rating ease of classification based on the time and the number of additional medical records required. Results were verified by an expert gynecologist, who also classified any malformations previously left unclassified. Data analysis used descriptive statistics. RESULTS: The non-expert successfully classified 859/920 patients (93.4%), rating classification as "easy" for 836/859 (90.9%) and "moderately difficult" for 23/859 (2.5%) patients. The expert gynecologist successfully classified 60 (60/920, 6.5%) of the remaining 61 patients rated as "difficult" by the non-expert, but was unable to accurately subclassify 1 patient (1/920, 0.1%) because the operative report lacked the relevant details. 251/920 (27.3%) patients had associated non-Müllerian anomalies, most frequently renal (20.9%) and skeletal (9.1%) malformations. CONCLUSIONS: The ESHRE/ESGE classification provides a generally applicable, comprehensive, and adequately specific classification of female genital tract congenital malformations. It offers an efficient basis for communication between non-experts and experts in the field and is, therefore, useful in clinical management and treatment planning.

Decidualization is Impaired in Endometrial Stromal Cells from Uterine Rudiments in Mayer-Rokitansky-Küster-Hauser Syndrome.

BACKGROUND/AIMS: Uterine rudiments from patients with Mayer-Rokitansky-Küster-Hauser syndrome (MRKHS) contain all tissues typically found in the uterus. Endometrium from the rudiments predominantly exhibits basalis-like features, and endometrial proliferative capacity in patients' epithelium and stroma is significantly lower. METHODS: This single-center, prospective study conducted at a major German university hospital compared in-vitro decidualization in cultured ESCs from MRKHS patients and hysterectomy controls. Primary ESC cultures were established from both sources. Hormone-induced prolactin and IGFBP-1 secretion served as a measure of their ability to undergo decidualization in response to hormonal stimulation. Expression levels of 8 key marker genes of decidualization were also determined. RESULTS: At day 9, mean secretion of prolactin and IGFBP-1 was significantly reduced by 89.0% and 99.5%, respectively, in MRKHS ESCs vs. hysterectomy controls, both indicating impaired decidualization of MRKHS ESCs. Key decidual markers confirmed impaired decidualization in MRKHS patients. CONCLUSION: Our results indicate that the ESCs from MRKHS patients lack hormone responsiveness as a potential sign of dysfunctional hormone receptor function, which may also play a role in the onset of MRKHS. Further studies are needed to corroborate our findings, directly address receptor function, and elucidate the role of other potential determinants of uterine development and adult function.

Second Opinion Expert Pathology in Endometrial Cancer: Potential Clinical Implications.

OBJECTIVE: In cancer patients, the pathology report serves as an important basis for treatment. Therefore, a correct cancer diagnosis is crucial, and diagnostic discrepancies may be of clinical relevance. It was the aim of this study to perform a specialized histopathology review and to investigate potential clinical implications of expert second opinion pathology in endometrial cancer. METHODS: Patients treated for endometrial carcinoma at the Tübingen University Women's hospital between 2003 and 2013 were identified. Original pathology reports were reviewed, and contributing pathologists were asked to submit original slides and paraffin blocks. Case review was subsequently performed by 3 pathologists specialized in gynecological pathology who were blinded for clinical information. For histological typing, the World Health Organization 2014 classification was used, grading and staging were performed according to International Federation of Gynecology and Obstetrics 2009. Risk assignment was performed based on the 2013 European Society for Medical Oncology clinical practice guidelines. RESULTS: In 565 of 745 cases, which had originally been diagnosed as endometrial carcinoma, archival histological slides and blocks were available. In 55 (9.7%) of 565 cases, a major diagnostic discrepancy of potential clinical relevance was found after expert review. In 38 of these 55 cases, the diagnostic discrepancy was related to tumor type (n = 24), grade (n = 10) or myoinvasion (n = 4). In 17 cases, the diagnosis of endometrial carcinoma could not be confirmed (atypical hyperplasia, n = 10; endometrial carcinosarcoma, n = 4; neuroendocrine carcinoma, n = 1; leiomyosarcoma, n = 1; atypical polypoid adenomyoma, n = 1). Minor discrepancies not changing risk classification were also noted in 214 (37.9%) of 565, most frequently for grade within the low-grade (G1/G2) category (n = 184). CONCLUSIONS: A retrospective gynecopathological case review was shown to reveal limited but significant discrepancies in histological diagnoses as well as typing and grading of endometrial carcinomas, some directly impacting clinical management. Second opinion pathology therefore not only helps to improve the quality of translational research study cohorts but might also help to optimize patient care in difficult cases.

Impact of apoptotic circulating tumor cells (aCTC) in metastatic breast cancer.

PURPOSE: While intact circulating tumor cells (iCTC) have independent negative prognostic impact on patients with metastatic breast cancer (MBC), the prognostic relevance of apoptotic CTC (aCTC) has not been validated in larger patient cohorts. This study assessed aCTC and iCTC statuses at baseline (CTCBL) and CTC kinetics (CTCKIN) as changes from CTCBL to one completed treatment cycle for their utility in predicting response, progression-free survival (PFS), and overall survival (OS) in MBC. METHODS: Status of iCTC and aCTC was prospectively assessed in 442 patients using the CellSearch™ system. Different cutoffs were analyzed both for iCTC and aCTC (≥5, ≥10, ≥25 and ≥50 CTC/7.5 ml). CTCKIN were characterized by ≥25 % changes in CTC counts. RESULTS: Numbers of iCTC and aCTC at baseline correlated strongly (r = 0.7). For iCTCBL positive patients, additional detection of aCTCBL had a significant prognostic impact on OS (aCTCBL positive 10.3 vs. aCTCBL negative 16.4 months, p = 0.012). Worst prognosis for OS was observed in patients with ≥50 iCTC/7.5 ml and simultaneously detected aCTC. Determination of aCTCKIN showed stronger discriminating power than iCTCKIN, with higher PFS and OS for the group with decreasing CTCs (PFS 7.7 vs. 6.1; OS 22.2 vs. 16.4). CONCLUSIONS: Intact and aCTC are predictive of outcome in MBC. Apoptotic CTC counts ≥ 5/7.5 ml in conjunction with iCTC at baseline have an independent unfavorable prognostic impact on OS. Decreasing aCTCKIN at ≥ 5/7.5 ml in serial enumeration is associated with favorable outcome. Therefore, separate enumeration of iCTC and aCTC is useful in tailoring systemic treatment.

Sexual Function Is Correlated With Body Image and Partnership Quality in Female University Students.

INTRODUCTION: According to the World Health Organization definition, sexual health is more than mere physical sexual function; it also encompasses emotional, mental, and social well-being in relation to sexuality and is not merely the absence of dysfunction or disease. In line with this definition, various studies have reported that female sexual function is associated with partnership quality, body image, and body self-acceptance. AIM: To investigate whether female sexual function is influenced by (i) body self-acceptance and (ii) partnership quality, as important factors in psychosocial well-being, and (iii) whether the effects of body self-acceptance are moderated by partnership quality. METHODS: In total, 2,685 female medical students no older than 35 years from Germany, Austria, and Switzerland completed an anonymous online questionnaire comprising the Female Sexual Function Index (FSFI) and the Self-Acceptance of the Body Scale. Respondents were asked to state whether they had been in a steady partnership in the preceding 6 months. When present, the quality of the partnership status was rated (enamoredness, love, friendship, or conflicted). To determine correlations, group differences, and moderating effects among body self-acceptance, partnership quality, and sexual function, the data were analyzed using Spearman correlations, Kruskal-Wallis tests, and analyses of variance. MAIN OUTCOME MEASURES: Female sexual function (FSFI total score). RESULTS: (i) In sexually active women, higher FSFI scores were significantly associated with greater body self-acceptance and a steady partnership during the preceding 6 months. (ii) Total FSFI scores were highest in women who described their partnership as enamored (29.45) or loving (28.55). Lower scores were observed in single women (26.71) and in women who described their partnerships as friendship (25.76) or as emotionally conflicted (23.41). (iii) Total FSFI score was affected by an interaction between body self-acceptance and partnership quality. Body self- acceptance was positively associated with FSFI total scores, particularly in single women and women in emotionally conflicted partnerships. CONCLUSION: Our findings suggest that in young women, body self-acceptance and partnership quality are positively associated with better sexual function, and that high body self-acceptance might buffer the negative impact on sexual function of partnership quality. The present data suggest that psychological interventions to improve the body image of younger women can positively affect sexual function and thereby improve sexual health.

Evaluation of the HystSim™-virtual reality trainer: an essential additional tool to train hysteroscopic skills outside the operation theater.

BACKGROUND: Minimally invasive surgery is a major pillar of gynecological surgery. However, there are very few training opportunities outside the operation theater (OR) due to the cost and equipment requirements of organ simulators, virtual reality trainers (VRT) are promising tools to fill this gap. METHODS: Experienced and inexperienced participants of a minimally invasive surgery course followed the standardized HystSim™-VRT training program. RESULTS: Performance of 39 Participants (15 inexperienced and 24 experienced) was evaluated in the standardized hysteroscopic program HystSim™. Tasks included three rounds of both a polyp and a myoma resection. Primary measurements were improvement in resection time, cumulative resection path length, and distention media use. CONCLUSION: The HystSim™-VRT is an effective tool to improve the psychomotor skills needed in hysteroscopic surgery for experienced and inexperienced surgeons prior to OR exposure. Additional organ models training is advisable for hysteroscopic haptic skills.

The impact of HER2 phenotype of circulating tumor cells in metastatic breast cancer: a retrospective study in 107 patients.

BACKGROUND: In metastatic breast cancer (MBC), antigen profiles of metastatic tissue and primary tumor differ in up to 20 % of patients. Reassessment of predictive markers, including human epidermal growth factor receptor 2 (HER2) expression, might help to optimize MBC treatment. While tissue sampling is invasive and often difficult to repeat, circulating tumor cell (CTC) analysis requires only a blood sample and might provide an easy-to-repeat, real-time "liquid biopsy" approach. The present retrospective study was conducted to compare HER2 expression in primary tumors, metastatic tissue, and circulating tumor cells (CTCs) from MBC patients and to analyze the potential impact of HER2 overexpression by CTCs on progression-free (PFS) and overall survival (OS) in MBC. METHODS: CTC-positive (five or more CTCs/7.5 mL blood; CellSearch®, Janssen Diagnostics) MBC patients starting a new line of systemic treatment were eligible for the study. HER2 status of CTCs was determined by immunofluorescence (CellSearch®). HER2 status of primary (PRIM) and metastatic (MET) tumor tissue was determined by immunohistochemistry. Data were analyzed using descriptive statistics and Kaplan-Meier plots. RESULTS: One hundred seven patients (median age (range) 57 (33-81) years) were included. 100/107 (93%) patients were followed-up for a median [95% confidence interval (CI)] of 28.5 [25.1-40.1] months. Of 37/107 (35%) CTC-HER2-positive patients only 10 (27%) were PRIM-HER2-positive. 6/46 (13%) patients were MET-HER2-positive; only 2/10 (20%) CTC-HER2-positive patients were MET-HER2-positive. Overall accuracy between CTC-HER2 expression and PRIM-HER2 and MET-HER2 status was 69% and 74%, respectively. Kaplan-Meier plots of PFS and OS by CTC-HER2 status revealed significantly longer median [95% CI] PFS of CTC-HER2-positive versus CTC-HER2-negative patients (7.4 [4.7-13.7] versus 4.34 [3.5-5.9] months; p = 0.035). CTC-HER2-positive status showed no significant difference for OS (13.7 [7.7-30.0] versus 8.7 [5.9-15.3] months; p = 0.287). CONCLUSIONS: HER2 status can change during the course of breast cancer. CTC phenotyping may serve as an easy-to-perform "liquid biopsy" to reevaluate HER2 status and potentially guide treatment decisions. Further, prospective studies are needed.

Are hormonal components of oral contraceptives associated with impaired female sexual function? A questionnaire-based online survey of medical students in Germany, Austria, and Switzerland.

PURPOSE: To investigate in a large cohort of young university women whether different progestins and different ethinyl estradiol (EE) dosages in oral hormonal contraceptives (OHCs) adversely affect sexual function. METHODS: Female medical students from German, Austrian, and Swiss universities (14/1/1) completed an anonymous online questionnaire comprising the 19 Female Sexual Function Index (FSFI) questions and 17 additional questions concerning demographics, lifestyle, sexual activity, and contraceptive use. OHCs were categorized by EE dose (≤20, <20 to ≤30, and >30 µg) and partially androgenic or antiandrogenic progestins. FSFI scores were analyzed by contraceptive method using descriptive statistics and standard nonparametric tests. RESULTS: We analyzed 2612 questionnaires submitted by respondents aged ≤30 years [mean age (SD) 23.5 (2.5) years]. Of 2126 contraceptive users, 1535 (72.2 %) used OHCs. Median FSFI total scores (ranges) were 28.2 (2.0-36.0) for all respondents. Median FSFI was significantly lower in non-users (24.4) versus users (28.7) of contraception (p < 0.001). Stratified analysis showed that 279/486 (57.4 %) respondents using no contraceptives, 563/1535 (36.7 %) using OHCs, 71/227 (31.3 %) using non-oral hormonal contraceptives, and 96/351 (27.4 %) using non-hormonal contraceptives were at risk for female sexual dysfunction (FSFI total score <26.55). FSFI scores for the three EE dosage categories and progestin components did not differ significantly. CONCLUSIONS: For OHCs, the FSFI score was lower than for other contraceptives but there was no significant association with EE dose or progestins, possibly due to small sample sizes. Further research needs to clarify the role of OHCs in female sexual function.

Serial enumeration of circulating tumor cells predicts treatment response and prognosis in metastatic breast cancer: a prospective study in 393 patients.

BACKGROUND: To prospectively assess circulating tumor cell (CTC) status at baseline (CTCBL) and after one cycle of a new line of systemic therapy (CTC1C), and changes from CTCBL to CTC1C (CTC kinetics, CTCKIN) for their utility in predicting response, progression-free (PFS) and overall survival (OS) in metastatic breast cancer (MBC). METHODS: CTCBL and CTC1C status was determined as negative (-) or positive (+) for < 5 or ≥ 5 CTCs/7.5 ml blood using CellSearch™ (Veridex). CTCKIN was categorized as favorable (CTC1C-) or unfavorable (CTC1C+). Tumor response was to be assessed every 2-3 months using the Response Evaluation Criteria in Solid Tumors (RECIST) criteria. Statistical analysis focused on the relation between CTC status and CTCKIN, and response, PFS, and OS. RESULTS: 133/393 (34%) patients enrolled were CTCBL+. CTC1C status after one cycle and radiological tumor response were assessed after median (range) periods of 1.2 (0.5-3.2) and 2.9 (0.5-4.8) months, respectively. 57/201 (28%) were CTC1C+. Median [95% confidence interval] PFS and OS (months) were significantly reduced in CTCBL+ vs. CTCBL- patients (PFS 4.7 [3.7-6.1] vs. 7.8 [6.4-9.2]; OS 10.4 [7.9-15.0] vs. 27.2 [22.3-29.9]), and for CTC1C+ vs. CTC1C- patients (PFS 4.3 [3.6-6.0] vs. 8.5 [6.6-10.4]; OS 7.7 [6.4-13.9] vs. 30.6 [22.6-not available]). Unfavorable CTCKIN was significantly associated with progressive disease. Multivariate Cox regression analysis revealed prognostic factors for shorter PFS (CTCBL+, persistent CTCs after one cycle, ≥ 3rd-line therapy, and triple-negative receptor status) and shorter OS (CTCBL+, persistent CTCs after one cycle, bone-and-visceral/local metastases, ≥ 3rd-line therapy, and triple-negative receptor status). CONCLUSIONS: CTCBL, CTC1C, and CTCKIN are predictive of outcome in MBC. Serial CTC enumeration is useful in tailoring systemic treatment of MBC. TRIAL REGISTRATION: Not applicable.

Bipolar vessel sealing: instrument contamination and wear have little effect on seal quality and success in a porcine in vitro model.

PURPOSE: The aim of this study is to systematically investigate under standardized experimental conditions the effects of instrument contamination and wear on the quality of bipolar vessel sealing (BVS) achieved using a reusable instrument. METHODS: The study was designed as a prospective, randomized, and controlled in vitro study and conducted in an academic research environment. Reusable bipolar coagulation forceps (BiClamp® 200 C, ERBE Elektromedizin) were used to apply sealing pressures of 300-1,100 mN/mm(2) to 239 renal arteries from commercially slaughtered female pigs (Swabian-Hall Swine). Forceps jaws were coated with porcine blood, blood and collagen, or blood, collagen, and fat to simulate instrument contamination with biological material during surgery. Clinical wear was mimicked by sandpaper abrasion. The main outcome measures were seal success (resistance to 250 mmHg intraluminal pressure for 2 min) and seal stability (burst pressure). RESULTS: Sealing pressure had a significant impact, with 800 mN/mm(2) producing the best sealing results. Seal success increased with total energy applied to the tissue, a higher maximum temperature, and longer coagulation as indicated by desiccation time. Experimental contamination had no significant impact on seal success and only a limited effect on seal stability. Similarly, abrasive wear also had no significant effect on either seal quality or seal strength. CONCLUSIONS: The impact of bipolar forceps contamination and wear on seal success and quality was negligible in our in vitro model. To achieve high-quality seals, it is essential to use adequate sealing pressures. Our findings could have direct implications for the design and clinical handling of BVS instruments.

Patient-reported quality-of-life and sexual-function outcomes after laparoscopic supracervical hysterectomy (LSH) versus total laparoscopic hysterectomy (TLH): a prospective, questionnaire-based follow-up study in 915 patients.

PURPOSE: To compare patient-reported quality-of-life and sexual function outcomes in women after laparoscopic supracervical hysterectomy (LSH) or total laparoscopic hysterectomy (TLH) for benign uterine disease. METHODS: Out of a cohort of 1,952 patients from a previous implementation study of LSH and TLH, 1,886 patients who had not undergone intraoperative conversion to laparotomy or were ineligible for other reasons were invited by mail to participate in this prospective, questionnaire-based follow-up study. RESULTS: Of the 915/1,952 (48.5 %) survey respondents included in the analysis, 788 (86.1 %) and 127 (13.9 %) had undergone LSH or TLH, respectively. Women undergoing LSH reported significantly lower pain levels (p = 0.037) and faster partial (p = 0.015) and complete (p < 0.001) resumption of normal daily activities compared to those undergoing TLH. As regards sexual function, women undergoing LSH resumed sexual activity significantly sooner (p = 0.018), rated sexual desire as higher (p = 0.023), and reported more frequently that their sexual life had improved postoperatively (p = 0.008) than did women undergoing TLH. CONCLUSIONS: Women undergoing LSH for benign uterine disease may have better outcomes regarding certain quality-of-life and sexual function parameters than women undergoing TLH for benign uterine disease.

A Cohort of 469 Mayer-Rokitansky-Küster-Hauser Syndrome Patients-Associated Malformations, Syndromes, and Heterogeneity of the Phenotype.

The Mayer-Rokitansky-Küster-Hauser syndrome is characterized by aplasia of the uterus and upper two-thirds of the vagina. While it can appear as an isolated genital malformation, it is often associated with extragenital abnormalities, with little still known about the pathogenetic background. To provide an overview of associated malformations and syndromes as well as to examine possible ties between the rudimentary tissue and patient characteristics, we analyzed a cohort of 469 patients with MRKHS as well as 298 uterine rudiments removed during surgery. A total of 165 of our patients (35.2%) had associated malformations (MRKHS type II). Renal defects were the most common associated malformation followed by skeletal abnormalities. Several patients had atypical associated malformations or combined syndromes. Uterine rudiments were rarer in patients with associated malformations than in patients without them. Rudiment size ranged from 0.3 cm3 to 184.3 cm3 with a mean value of 7.9 cm3. Importantly, MRKHS subtype or concomitant malformations were associated with a different frequency of uterine tissue as well as a different rudiment size and incidence of endometrial tissue, thereby indicating a clear heterogeneity of the phenotype. Further research into the associated molecular pathways and potential differences between MRKHS subtypes is needed.

Laparoscopic supracervical hysterectomy (LSH) versus total laparoscopic hysterectomy (TLH): an implementation study in 1,952 patients with an analysis of risk factors for conversion to laparotomy and complications, and of procedure-specific re-operations.

PURPOSE: To compare laparoscopic supracervical hysterectomy (LSH) with total laparoscopic hysterectomy (TLH) with regard to relevant surgical parameters and risk factors of conversion to laparotomy and complications. METHODS: This prospective, open, single-center, interventional study included women with benign gynecologic disease who underwent standardized LSH or TLH. The techniques were compared for conversion rate and mean operating time, hemoglobin drop, hospital stay, and complication rates using descriptive statistics and standard non-parametric statistical tests. Risk factors of conversion and complications were identified by logistic regression analysis. RESULTS: During January 2003 to December 2010, 1,952 women [mean age (SD): 47.5 (7.2) years] underwent LSH [1,658 (84.9%)] or TLH [294 (15.1%)], mostly (>70%) for uterine fibroids. Significant differences in surgical parameters were observed for conversion rate (LSH/TLH: 2.6/6.5%), mean operating time [87 (34)/103 (36) min], hemoglobin drop [1.3 (0.8)/1.6 (1.0) g/dL], and hospital stay [4.3 (1.5)/4.9 (2.8) days]. Overall intraoperative (0.2/0.7%) and long-term (>6 weeks) post-operative (0.8/1.7%) complication rates did not differ significantly, but the short-term LSH complication rate was significantly lower (0.6 vs. 4.8%). Spotting (LSH, 0.2%) and vaginal cuff dehiscence (TLH, 0.7%) were long-term method-specific complications. Logistic regression showed that uterine weight and extensive adhesiolysis were significant factors for conversion while previous surgery, age, and BMI were not. Major risk factors of short-term complications were age, procedure (LSH/TLH), and extensive adhesions. CONCLUSIONS: Both procedures proved effective and were well tolerated. LSH performed better than TLH regarding most outcome measures. LSH is associated with very low rates of re-operation and spotting.

Tumor-Free Resection Margin Distance in the Surgical Treatment of Node-Negative Squamous Cell Cancer of the Vulva Has No Impact on Survival: Analysis of a Large Patient Cohort in a Tertiary Care Center.

BACKGROUND: The aim of this study was to evaluate the impact of pathological tumor-free margin distance on survival in SCC patients treated with surgery alone. METHODS: This retrospective study included 128 patients with node-negative disease that received no adjuvant treatment. Disease-free and overall survival were analyzed according to pathological tumor-free margin distance. RESULTS: The patients were subclassified into three resection margin category groups: "1 to 3 mm" (n = 42), ">3 to 8 mm" (n = 47) or ">8 mm" (n = 39). Thirty-nine of the 128 patients (30.5%) developed recurrent disease. Median follow-up for disease-free survival (DFS) was 6.49 years (95% CI 5.16 years; 7.62 years), and median follow-up for overall survival (OS) was 6.29 years (95% CI 5.45 years; 7.33 years). The 5-year DFS rate was 0.70 (95% CI: 0.62-0.79), and the 5-year OS rate was 0.79 (95% CI: 0.71-0.87). Regarding the survival outcome, there were no independent significant differences in either disease-free survival (DFS) (p = 0.300) or overall survival (p = 1.000) among patients within the three tumor-free resection margin categories. Multivariate analyses did not show any statistically significant association between tumor-free resection margin distance and recurrent disease or death, either when analyzed as a categorical variable or when analyzed as a continuous variable. CONCLUSION: The present study did not show a significant impact of pathological tumor-free resection margin distance following surgery in patients with node-negative SCC of the vulva (that did not receive adjuvant treatment) on disease-free and overall survival.

Molecular detection of breast cancer metastasis in sentinel lymph nodes by reverse transcriptase polymerase chain reaction (RT-PCR): identifying, evaluating and establishing multi-marker panels.

The potential advantage of using quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) methodology to detect metastasis in sentinel lymph nodes (SLNs) of breast cancer (BC) patients was evaluated in this prospective study. We measured the expression of relevant gene transcripts in SLNs using an innovative algorithm and compared the results of single-marker assays versus multi-marker assays with conventional histological detection methods. SLNs from women aged ≥ 18 years diagnosed with unilateral BC were examined by haematoxylin-eosin staining and immunohistochemistry and analysed for transcripts of several relevant genes using qRT-PCR (learning group). Four candidate panels of expressed transcript combinations with high sensitivity and specificity were selected for further investigation. The candidate panels were then validated using SLNs from a second group of BC patients (validation group). In the learning group, 74/314 SLN sections from 150 patients were positive for metastasis by histology. The transcripts analysed showed the following individual sensitivities/specificities: cytokeratin 19 (CK19) 94.6%/97.9%; mammaglobin 1 (MGB1) 82.4%/91.7%; mammaglobin 2 (MGB2) 82.4%/96.7%; carcinoembryonic antigen (CEA) 71.6%/97.5%; EPCAM (epithelial cell adhesion molecule) 91.9%/97.1%; and NY-BR-1 82.4%/93.8%. The optimal panel based on the predefined criteria comprised four markers: CK19, MGB1, EPCAM, and NY-BR-1, of which ≥ 2 had to be positive (95.9% sensitivity, 95.0% specificity, 85.5% positive predictive value (PPV), and 98.7% negative predictive value (NPV)). Overall concordance with histology was 95.2%. In the validation group, 84/315 SLN sections from 235 patients were histologically positive, and panel sensitivity, specificity and overall accuracy were 88.1, 95.2 and 93.3%, respectively, at the SLN section level. In conclusion, molecular staging using expression patterns of relevant transcripts in SLNs could serve as a useful complement to standard diagnostic work-up in BC patients. The proposed flexible multi-parametric approach does not improve the overall accuracy compared with the single-marker approach. However, it overcomes several limitations of the previously reported molecular assays for SLN diagnosis.

Long Term Findings Concerning the Mental and Physical Condition, Quality of Life and Sexuality after Laparoscopically Assisted Creation of a Neovagina (Modified Vecchietti Technique) in Young MRKHS (Mayer-Rokitansky-Küster-Hauser-Syndrome) Patients.

The Mayer-Rokitansky-Küster-Hauser-syndrome (MRKHS) is characterized by a congenital uterine and vaginal aplasia. A large body of literature reports that a diagnosis of MRKHS has a variety of psychological effects on patients and doubts about female identity. The aim of the underlying study was to detect the patient-reported physical and mental health and sexual function before and after laparoscopically assisted creation of a neovagina. 160 women with MRKHS who underwent this type of surgery between September 2009 and December 2015 were invited to complete the questionnaires. Packages consisting of six questionnaires were handed out before surgery, six and 12 months after surgery. Data from 82 patients could be included in the study. Patients had a mean age of 19.9 years at inclusion in the study. We detected an impairment of the health-related mental quality of life. There was no higher risk for psychological disorders. MRKHS patients show similar self-acceptance and normal body image compared to the general population. The sexual function is limited before surgery and normalizes after surgery. Useful factors for coping with the disease are an interdisciplinary approach in diagnostics and treatment, psychosocial adaptation as well as a supportive social environment.

Analysis of risk factors determining prognosis of cutaneous squamous-cell carcinoma: a prospective study.

BACKGROUND: Cutaneous squamous-cell carcinomas (SCC) are among the most common cancers capable of metastasis. Current Tumour Node Metastasis (TNM) staging includes horizontal tumour size, involvement of extradermal structures, and degree of differentiation. The aim of this study was to prospectively analyse the key factors predicting metastasis and local recurrence in cutaneous SCC. METHODS: We assessed prospectively investigated potential risk factors for metastasis or local recurrence of SCC, previously suggested by retrospective studies and small case series, in 615 white patients. Between Jan 1, 1990, and Dec 31, 2001, all patients underwent surgery for cutaneous SCC with complete histological examination of the three-dimensional excision margins (3D-histology) in one centre. Univariate and multivariate analysis included tumour thickness, horizontal size, body site, histological differentiation, desmoplastic growth, history of multiple SCC, and immunosuppression. Primary endpoints were time to metastasis and time to local recurrence, defined as the time from date of diagnosis of the primary tumour to the date of diagnosis of metastasis or local recurrence, respectively. FINDINGS: 653 patients were enrolled in the study. 38 patients were lost to follow-up leaving 615 assessable patients (median age 73 years [range 27-98]). During a median follow-up period of 43 months (range 1-165), 26 (4%) of 615 patients developed metastases and 20 patients developed local recurrence (3%). Tumours 2.0 mm or less in thickness did not metastasise. Metastases occurred in 12 (4%) of 318 tumours between 2.1 mm and 6.0 mm in thickness, and in 14 (16%) of 90 tumours with a thickness greater than 6.0 mm. On multivariate analysis, key prognostic factors for metastasis were increased tumour thickness (hazard ratio 4.79 [95% CI 2.22-10.36]; p<0.0001), immunosuppression (4.32 [1.62-11.52]; p=0.0035), localisation at the ear (3.61 [1.51-8.67]; p=0.0040), and increased horizontal size (2.22 [1.18-4.15]; p=0.0128). The risk of local recurrence depended on increased tumour thickness (6.03 [2.71-13.43]; p<0.0001) and desmoplasia (16.11 [6.57-39.49]; p<0.0001). INTERPRETATION: Only SCC greater than 2.0 mm in thickness are associated with a significant risk of metastasis. Tumours greater than 6.0 mm are associated with a high risk of metastasis and local recurrence. Desmoplastic growth is an independent risk factor for local recurrence. Studies should assess the role of follow-up visits and sentinel-lymph-node biopsy in high-risk patients.