Prognostic impact of selection criteria of current adjuvant endocrine therapy trials NATALEE and monarchE in postmenopausal HRpos/HER2neg breast cancer patients treated with upfront letrozole.

BACKGROUND: The monarchE and NATALEE trials demonstrated the benefit of CDK4/6 inhibitor (CDK4/6i) therapy in adjuvant breast cancer (BC) treatment. Patient selection, based on clinical characteristics, delineated those at high (monarchE) and high/intermediate recurrence risk (NATALEE). This study employed a historical patient cohort to describe the proportion and prognosis of patients eligible for adjuvant CDK4/6i trials. METHODS: Between 2009 and 2011, 3529 patients were enrolled in the adjuvant PreFace clinical trial (NCT01908556). Eligibility criteria included postmenopausal patients with hormone receptor-positive (HRpos) BC for whom a five-year upfront therapy with letrozole was indicated. Patients were categorized into prognostic groups according to monarchE and NATALEE inclusion criteria, and their invasive disease-free survival (iDFS) and overall survival (OS) were assessed. RESULTS: Among 2891 HRpos patients, 384 (13.3 %) met the primary monarchE inclusion criteria. The majority (n = 261) qualified due to having ≥ 4 positive lymph nodes. For NATALEE, 915 out of 2886 patients (31.7 %) met the eligibility criteria, with 126 patients (13.7 %) being node-negative. Patients from monarchE with ≥ 4 positive lymph nodes and NATALEE with stage III BC exhibited the poorest prognosis (3-year iDFS rate 0.87). Patients ineligible for the trials demonstrated prognoses similar to the most favorable patient groups within the eligibility criteria. CONCLUSION: Patient populations eligible for monarchE and NATALEE trials differed. Nearly a third of the postmenopausal HRpos population, previously under upfront letrozole treatment, met the NATALEE prognostic eligibility criteria. As certain eligible groups had a prognosis similar to non-eligible patients, it might be interesting to explore additional patient groups for CDK4/6i therapy.

Acute and Long-Term Toxicity after Planned Intraoperative Boost and Whole Breast Irradiation in High-Risk Patients with Breast Cancer-Results from the Targeted Intraoperative Radiotherapy Boost Quality Registry (TARGIT BQR).

In the context of breast cancer treatment optimization, this study prospectively examines the feasibility and outcomes of utilizing intraoperative radiotherapy (IORT) as a boost in combination with standard external beam radiotherapy (EBRT) for high-risk patients. Different guidelines recommend such a tumor bed boost in addition to whole breast irradiation with EBRT for patients with risk factors for local breast cancer recurrence. The TARGIT BQR (NCT01440010) is a prospective, multicenter registry study aimed at ensuring the quality of clinical outcomes. It provides, for the first time, data from a large cohort with a detailed assessment of acute and long-term toxicity following an IORT boost using low-energy X-rays. Inclusion criteria encompassed tumors up to 3.5 cm in size and preoperative indications for a boost. The IORT boost, administered immediately after tumor resection, delivered a single dose of 20 Gy. EBRT and systemic therapy adhered to local tumor board recommendations. Follow-up for toxicity assessment (LENT SOMA criteria: fibrosis, teleangiectasia, retraction, pain, breast edema, lymphedema, hyperpigmentation, ulceration) took place before surgery, 6 weeks to 90 days after EBRT, 6 months after IORT, and then annually using standardized case report forms (CRFs). Between 2011 and 2020, 1133 patients from 10 centers were preoperatively enrolled. The planned IORT boost was conducted in 90%, and EBRT in 97% of cases. Median follow-up was 32 months (range 1-120, 20.4% dropped out), with a median age of 61 years (range 30-90). No acute grade 3 or 4 toxicities were observed. Acute side effects included erythema grade 1 or 2 in 4.4%, palpable seroma in 9.1%, punctured seroma in 0.3%, and wound healing disorders in 2.1%. Overall, chronic teleangiectasia of any grade occurred in 16.2%, fibrosis grade ≥ 2 in 14.3%, pain grade ≥ 2 in 3.4%, and hyperpigmentation in 1.1%. In conclusion, a tumor bed boost through IORT using low-energy X-rays is a swift and feasible method that demonstrates low rates in terms of acute or long-term toxicity profiles in combination with whole breast irradiation.

Correction: Long-term Follow-up and Safety of Patients after an Upfront Therapy with Letrozole for Early Breast Cancer in Routine Clinical Care - The PreFace Study.

[This corrects the article DOI: 10.1055/a-2238-3153.].

Long-term Follow-up and Safety of Patients after an Upfront Therapy with Letrozole for Early Breast Cancer in Routine Clinical Care - The PreFace Study.

Introduction: Adjuvant treatment of patients with early-stage breast cancer (BC) should include an aromatase inhibitor (AI). Especially patients with a high recurrence risk might benefit from an upfront therapy with an AI for a minimum of five years. Nevertheless, not much is known about the patient selection for this population in clinical practice. Therefore, this study analyzed the prognosis and patient characteristics of postmenopausal patients selected for a five-year upfront letrozole therapy. Patients and Methods: From 2009 to 2011, 3529 patients were enrolled into the adjuvant phase IV PreFace clinical trial (NCT01908556). Postmenopausal hormone receptor-positive BC patients, for whom an upfront five-year therapy with letrozole (2.5 mg/day) was indicated, were eligible. Disease-free survival (DFS), overall survival (OS) and safety in relation to patient and tumor characteristics were assessed. Results: 3297 patients started letrozole therapy. The majority of patients (n = 1639, 57%) completed the five-year treatment. 34.5% of patients continued with endocrine therapy after the mandated five-year endocrine treatment. Five-year DFS rates were 89% (95% CI: 88-90%) and five-year OS rates were 95% (95% CI: 94-96%). In subgroup analyses, DFS rates were 83%, 84% and 78% for patients with node-positive disease, G3 tumor grading, and pT3 tumors respectively. The main adverse events (any grade) were pain and hot flushes (66.8% and 18.3% of patients). Conclusions: The risk profile of postmenopausal BC patients selected for a five-year upfront letrozole therapy showed a moderate recurrence and death risk. However, in subgroups with unfavorable risk factors, prognosis warrants an improvement, which might be achieved with novel targeted therapies.

The effectiveness of integrated online health-coaching on physical activity and excessive gestational weight gain: a prospective randomized-controlled trial.

PURPOSE: Low levels of physical activity during pregnancy go along with increased risks for numerous health complications. We investigated whether an integrated lifestyle intervention leads to higher levels of physical activity and reduces the rate of excessive gestational weight gain (EGWG). METHODS: We conducted a randomized-controlled trial on 97 pregnant women, randomly assigned to receive an additional telehealth lifestyle intervention (experimental group, EG; n = 49) or conventional antenatal care (control group, CG; n = 48). The core lifestyle intervention comprised regular video calls, providing integrated personal support and motivation to physical activity. The primary outcome was change in physical activity measured in steps per day. An additional exploratory outcome was the proportion of participants with EGWG. RESULTS: The mean step count during the third trimester was 6483 steps/day (EG) and 5957 steps/day (CG), respectively (p = 0.078). Repeated-measures ANOVA revealed a significant interaction effect (p = 0.045) reflecting an overall increase of 497 steps per day in the EG vs. a decrease of 300 steps per day in the CG. The proportion of participants who met the IOM recommendation for total weight gain during pregnancy was significantly higher in the EG (p = 0.048) and the ratio of women that gained excessively was higher in the CG (p = 0.026). CONCLUSIONS: We assume that the personalized online intervention supports women in increasing or at least maintaining their level of physical activity during the course of pregnancy. Additionally, it reduces the rate of excessive weight gain.

Intraoperative radiotherapy (IORT) of early breast cancer with low-energy x-rays in breast-conserving surgery : Prospective identification of pre- and intraoperative factors influencing the feasibility of IORT.

PURPOSE: The aim of this study is to identify pre- and intraoperative factors indicating the feasibility of intraoperative radiotherapy (IORT) during breast-conserving surgery (BCS). MATERIALS AND METHODS: From January 2018 to December 2019, a total of 128 women undergoing BCS due to early breast cancer were included in this prospective observational study, independent of whether IORT was planned or not. Patient and tumor characteristics as well as surgical parameters that could potentially influence the feasibility of IORT were recorded for the entire collective. In addition, a preoperative senological assessment was performed and analyzed to assess the feasibility of IORT. Logistic regression was then used to identify relevant preoperative parameters and to generate a formula predicting the feasibility of IORT. RESULTS: Of the 128 included women undergoing BCS, 46 were preoperatively rated to be feasible, 20 to be questionably feasible for IORT. Ultimately, IORT was realized in 30 patients. The most frequent reasons for omission of IORT were insufficient tumor-to-skin distance and/or an excessively large tumor cavity. Small clinical tumor size and large tumor-to-skin distance according to preoperative ultrasound were significantly related to accomplishment of IORT. CONCLUSION: We observed that preoperative ultrasound-based tumor-skin distance is a significant factor in addition to already known parameters to predict feasibility of IORT. Based on our findings we developed a formula to optimize IORT planning which might serve as an additional tool to improve patient selection for IORT in early breast cancer.

Relationship of Ki-67 index in biopsies of metastatic breast cancer tissue and circulating tumor cells (CTCs) at the time of biopsy collection.

BACKGROUND: The proliferation marker Ki-67 is a major pathological feature for the description of the state of disease in breast cancer. It helps to define the molecular subtype and to stratify between therapy regimens in early breast cancer and helps to assess the therapy response. Circulating tumor cells (CTCs) are a negative prognostic biomarker for progression free (PFS) and overall survival (OS) in patients with metastatic breast cancer. Therefore, the CTC count is often described as surrogate for the tumor burden. Both, decrease of Ki-67 and CTC count are considered as evidence for therapy response. The presented work analyzed the correlation between the Ki-67 indices of metastatic tissue biopsies and CTC counts in biopsy time-adjacent peripheral blood samples. PATIENTS AND METHODS: Blood samples from 70 metastatic breast cancer patients were obtained before the start of a new line of systemic therapy. CTCs were enumerated using CellSearch® (Menarini Silicon Biosystems, Bologna, Italy) whereas intact CTCs (iCTCs) and non-intact or apoptotic CTCs (aCTCs) were distinguished using morphologic criteria. The proportion of cells expressing Ki-67 was evaluated using immunohistochemistry on biopsies of metastases obtained concurrently with CTC sampling before the start of a new line of systemic therapy. RESULTS: 65.7% of patients had a Ki-67 index of > 25%. 28.6% of patients had ≥ 5, 47.1% ≥ 1 iCTCs. 37.1% had ≥ 5, 51.4% ≥ 1 aCTCs. No correlation was shown between Ki-67 index and iCTC and aCTC count (r = 0.05 resp. r = 0.05, Spearman's correlation index). High CTC-counts did not coincide with high Ki-67 index. High Ki-67, ≥ 5 iCTCs and aCTCs are associated with poor progression free (PFS) and overall survival (OS). CONCLUSION: CTCs and Ki-67 are independent prognostic markers in metastatic breast cancer. High Ki-67 in metastatic tumor tissue is not correlated to high iCTC or aCTC counts in peripheral blood.

Major complications after intraoperative radiotherapy with low-energy x-rays in early breast cancer.

PURPOSE: To describe and analyze major local complications after intraoperative radiotherapy (IORT) with low-energy x­rays during breast-conserving surgery (BCS) in early breast cancer. METHODS: Ten women out of 408 who were treated with IORT between 2002 and 2017 and subsequently developed a severe local complication requiring surgical intervention were retrospectively identified and analyzed. Demographic, clinical, and surgical parameters as well as complication characteristics and treatment methods were evaluated. RESULTS: At initial presentation, eight patients (80%) showed redness, six (60%) seroma, six (60%) wound infection, six (60%) suture dehiscence, and four (40%) induration of the former surgical area. Hematoma and necrosis were observed in one case (10%) each. Time interval until appearance of the first symptoms ranged from directly postoperative until 15 years postoperatively (median 3.1 months). Initial treatment modalities comprised antibiotic therapy (n = 8/80%) and transcutaneous aspiration of seroma (n = 3/30%). In the majority of patients, smaller surgical interventions (excision of a necrotic area/fistula [n = 6/60%] or secondary suture [n = 5/50%]) were sufficient to overcome the complication, yet larger interventions such as complex flap surgery and mastectomy were necessary in one patient each. CONCLUSION: IORT is an efficient and safe treatment method as < 2.5% of all IORT patients experienced major local complications. However, it seems to pose the risk of causing severe local complications that may require lengthy and burdensome treatment. Thorough preoperative counseling, implementation of recommended intraoperative precautions, and high vigilance for first symptoms of complications during follow-up appointments are necessary measures.

Laparoscopic Fertility-Sparing Surgery for Early Ovarian Malignancies.

The demand for fertility-sparing surgery (FSS) has increased in the last decade due to increased maternal age, increased incidence of ovarian malignancies in younger patients, and technical advances in surgery. Data on oncological safety and fertility outcomes of patients with ovarian cancer after laparoscopic FSS are sparse, but some retrospective studies have shown that open FSS may be offered to selected patients. We assessed the role of minimally invasive FSS in comparison with radical surgery (RS) in terms of oncological safety and reproductive outcomes after FSS in this multicenter study. Eighty patients with FIGO stage I/II ovarian cancer treated with laparoscopic FSS or RS between 01/2000 and 10/2018 at the participating centers (comprehensive gynecological cancer centers with minimally invasive surgical expertise) were included in this retrospective analysis of prospectively kept data. Case-control (n = 40 each) matching according to the FIGO stage was performed. Progression-free survival [150 (3-150) and 150 (5-150) months; p = 0.61] and overall survival [36 (3-150) and 50 (1-275) months; p = 0.65] did not differ between the FSS and RS groups. Eight (25.8%) women became pregnant after FSS, resulting in seven (22.5%) deliveries; three (37.5%) patients conceived after in vitro fertilization, and five (62.5%) conceived spontaneously. Laparoscopic FSS seems to be applicable and oncologically safe for patients with early-stage ovarian cancer, with adequate fertility outcomes.

Longitudinal cosmetic outcome after planned IORT boost with low kV X-rays-monocentric results from the TARGIT BQR registry.

Background: Intraoperative radiotherapy can serve as an anticipated boost (IORT boost) in combination with a subsequent external whole breast irradiation in high-risk breast cancer patients and is part of many guidelines. Nevertheless, there are only few prospective data available regarding cosmetic outcome after IORT boost using kV X-rays. The aim of this study was to evaluate the cosmetic outcome of patients treated within the prospective phase IV TARGeted Intraoperative radioTherapy (TARGIT) Boost Quality Registry (BQR) study (NCT01440010) in one center. Methods: In the context of the TARGIT BQR study standardized photos in three positions (arms down, arms up, from the side) were available for different time points. For this analysis a layperson, a radiation oncologist and a gynecologist evaluated available photos at different time points during follow-up with up to 4 years using the Harvard scale (comparison of treated and the untreated breast; rating: excellent, good, fair, poor). Longitudinal results were compared to preoperative results (baseline). Results: Seventy-three patients were available for the analysis. Baseline cosmetic assessment was excellent/good in 98.8% (mean value for all three positions). Postoperative cosmetic outcome (median) was good for all positions and remained constant for 4 years. Around 30% of the patients showed a constant or even improved cosmetic outcome compared to baseline. Only few patients showed a poor result at 4 years. The majority of patients showed an excellent or good cosmetic outcome at all time points. Conclusions: Patients from the prospective TARGIT BQR study treated with IORT boost and additional whole breast irradiation showed good or excellent cosmetic outcomes in most cases during 4 years of follow-up. These results add important information for shared decision making in breast cancer patients.

Patient Preferences With Regard to Care Structures for Cervical or Vulvar Dysplasia in Certified Dysplasia Clinics in Germany.

BACKGROUND/AIM: The aim of this study was to evaluate patient preferences regarding cervical dysplasia clinics. Specifically, preferences in terms of diagnostic and therapeutic pathways as well as logistical and structural aspects were addressed to recognize unmet needs and improve existing structures of cervical dysplasia care. PATIENTS AND METHODS: This questionnaire-based study was conducted between June and December 2022 at an academic medical center in Southwestern Germany. A total of 226 patients who had an appointment at the certified dysplasia clinic were included. RESULTS: The vast majority of patients (74.8%) preferred counseling at the certified dysplasia clinic in the case of an abnormal finding of the cervix or labia. A prompt appointment (within a maximum of 4 weeks), a timely notification about test results (within a maximum of 2 weeks), a travel time <60 minutes and seeing the same doctor during follow-up appointments were recognized as important aspects. While about half of the patients (53.5%) were indifferent to the sex of the gynecologist, almost all of the remaining patients stated they would prefer to be seen by a female doctor (44.3% female doctor vs. 2.2% male doctor). CONCLUSION: Most women expect very timely appointments and result notifications. Moreover, they favor short travel times and continuity of care. The identified patient preferences should be considered to increase patient satisfaction and quality of care when developing and optimizing management at specialized dysplasia clinics.

Resistance to mesenchymal reprogramming sustains clonal propagation in metastatic breast cancer.

The acquisition of mesenchymal traits is considered a hallmark of breast cancer progression. However, the functional relevance of epithelial-to-mesenchymal transition (EMT) remains controversial and context dependent. Here, we isolate epithelial and mesenchymal populations from human breast cancer metastatic biopsies and assess their functional potential in vivo. Strikingly, progressively decreasing epithelial cell adhesion molecule (EPCAM) levels correlate with declining disease propagation. Mechanistically, we find that persistent EPCAM expression marks epithelial clones that resist EMT induction and propagate competitively. In contrast, loss of EPCAM defines clones arrested in a mesenchymal state, with concomitant suppression of tumorigenicity and metastatic potential. This dichotomy results from distinct clonal trajectories impacting global epigenetic programs that are determined by the interplay between human ZEB1 and its target GRHL2. Collectively, our results indicate that susceptibility to irreversible EMT restrains clonal propagation, whereas resistance to mesenchymal reprogramming sustains disease spread in multiple models of human metastatic breast cancer, including patient-derived cells in vivo.

Therapy Guidance by Vaginal Smears of Pregnant Women With Preterm Complications in Correlation With Maternal and Neonatal Outcome: A Retrospective Analysis.

BACKGROUND/AIM: This retrospective cohort study enrolled hospitalized women with 24+0 to 33+6 gestational weeks with conditions associated with preterm birth. We evaluated the ability of vaginal swab isolates to guide antibiotic management decisions in the setting of threatened preterm towards a clinical advantage, i.e., longer delay between diagnosis and birth, better neonatal outcomes. PATIENTS AND METHODS: Vaginal swabs were obtained from all patients and antibiotic resistance profiles determined in case of growth. The cohort was divided into two groups: the antibiogram-noncongruently managed Group 1 and the antibiogram-congruently managed Group 2. These groups were compared in regard to multiple maternal and neonatal endpoints. RESULTS: In total, 698 cases were analyzed - 224 in Group 1 and 474 in Group 2. Antibiotics were ordered/continued by the treating physician in 138 cases (138/698; 19.8%) upon review of vaginal swab cultures results. Forty-five among them (32.6%) received antibiotics inactive against the isolated bacteria. 335 (25.4%) patients had only normal vaginal flora, and 95.6% of them had not received antibiotics. Facultatively pathogenic microorganisms were isolated in 52% patients. Only 5% of the neonates had bacterial isolates identical to those of their mothers. There were no significant differences in outcomes between Group 1 and Group 2. CONCLUSION: No association was found between a swab-result-guided antibiotic management protocol and maternal or fetal outcome in the setting of preterm birth risk between 24 and 34 gestational weeks. These findings underline the importance of critical rethinking the frequency of vaginal smears and fine-tuning the indications for antibiotic treatment.

Prevalence of higher-grade dysplasia in persistently high-risk human papillomavirus positive, cytology negative women after introduction of the new cervical cancer screening in Germany.

PURPOSE: According to the recently implemented organized cervical cancer screening program in Germany, women older than 35 years with negative cytology but persistent high-risk human papilloma virus (hrHPV) infection > 12 months should be referred to colposcopy for further evaluation. This study aimed to present and dissect colposcopic and histopathological findings with particular focus on associated hrHPV genotypes. METHODS: This study is a retrospective analysis of clinical data from 89 hrHPV positive patients with normal cytology who underwent colposcopic examination at a certified dysplasia outpatient clinic in Germany in 2021. RESULTS: While 38 (43%) women had a normal colposcopic finding, 45 (51%) had minor and 6 (7%) major changes. Thirty-one (35%) of the women were HPV 16 and/or HPV 18 positive and 58 (65%) women were positive for other hrHPV only. Among patients who underwent colposcopy with biopsies (in case of an abnormal finding or type 3 transformation zone, n = 68), eight (12%) had cervical intraepithelial neoplasia (CIN) 3 and six (9%) had CIN 2. The proportion of women diagnosed with CIN 3 varied among different hrHPV genotypes (HPV 16: 11%, HPV 18: 33%, HPV 31: 27%, HPV 33: 33%, HPV 52: 33%). CONCLUSION: Persistently hrHPV positive women with negative cytology are at increased risk of being diagnosed with CIN 3. As CIN 3 prevalence seems to differ with regard to hrHPV strain, immediate HPV genotyping for risk stratification and subsequent early referral for colposcopy might constitute a feasible strategy.

Forensic Medical Examination After Sexual Violence: Implications Based on Victims' Perceptions.

BACKGROUND/AIM: The objective of this study was to assess the perception of the forensic medical examination (FME) by victims of sexual violence. Based on patient-related outcomes gained in terms of personnel, chronological and spatial parameters, an additional aim was to derive improved examination procedures. PATIENTS AND METHODS: A total of 49 sexually assaulted women were enrolled in this study. After standardized FME by a forensic doctor followed by a gynecologist, women were asked to complete a questionnaire addressing general perception, preferences regarding attending staff's sex, sequence and time frame of the examinations performed. The attending gynecologist also completed a questionnaire addressing demographic and medical parameters of the patient as well as assault-related information. RESULTS: The examination setting in general was evaluated positively. Nevertheless, 52% of examined victims perceived the FME as an additional psychological burden. Overall, 85% of the affected women preferred a female forensic physician and 76% a female gynecologist to perform the examination. When women said they experienced a violation of their privacy during the gynecological examination, a male was more often present (60% vs. 35%, p=0.0866). Regarding the sequence of the examination components, 65% of the victims preferred to start with their medical history followed by the forensic and then the gynecological examination. CONCLUSION: Forensic medical and gynecological examination after sexual assault is an essential procedure, yet it is a potentially further traumatizing experience for the victim. The identified patient preferences should be taken into account in order to diminish further trauma.

Microscopic, Macroscopic and Thermal Impact of Argon Plasma, Diode Laser, and Electrocoagulation on Ovarian Tissue.

BACKGROUND/AIM: To compare the microscopic, macroscopic and thermal damage inflicted to ovarian tissue by conventional monopolar and bipolar energy, argon plasma coagulation (APC) and diode laser. MATERIALS AND METHODS: Bovine ovaries were used as a substitute for human tissue and subjected to the four aforementioned techniques and the inflicted damage was measured. Sixty fresh and morphologically similar cadaveric bovine ovaries were divided into five equal groups, each group was subjected to one of the following energy applications for both 1 and 5 s: Monopolar, bipolar electrocoagulation, diode laser, preciseAPC® and forcedAPC® Ovarian temperatures were measured at 4 and 8 s after treatment. Formalin-fixed ovarian specimens were examined by pathologists regarding macroscopic, microscopic and thermal tissue damage. RESULTS: None of the ovaries reached the temperature producing severe damage (40°C) after 1 s of energy transfer. Heating of adjacent ovarian tissue was least pronounced when preciseAPC® and monopolar electrocoagulation were applied (27.2±3.3°C and 28.2±2.9°C after 5 s of application, respectively). Conversely, 41.7% of the ovaries subjected to bipolar electrocoagulation for 5 s overheated. ForcedAPC® resulted in the most pronounced lateral tissue defects (2.8±0.3 mm after 1 s and 4.7±0.6 mm after 5 s). When the modalities were applied for 5 s, the electrosurgical instruments (mono- and bipolar) and preciseAPC® induced similar lateral tissue damage (1.3±0.6 mm, 1.1±1.6 mm and 1.2±1.3 mm, respectively). preciseAPC® created the shallowest defect of all the techniques (0.05±0.1 mm after 5 s of application). CONCLUSION: Our study hints at superior safety profiles of preciseAPC® and monopolar electrocoagulation compared to bipolar electrocoagulation, diode laser and forcedAPC® for ovarian laparoscopic surgery.

Operator Sex and Experience Do Not Influence Conization Outcomes in Terms of Cone Volume, Depth or Resection Margins.

BACKGROUND/AIM: Conization in patients with cervical intraepithelial neoplasia is associated with longer time required to conceive, a higher risk of preterm delivery, and a myriad of obstetric complications. This study assessed whether operator sex and experience correlate with cone volume, depth, and resection margins in patients wishing to conceive and the general patient population. PATIENTS AND METHODS: This retrospective single center cohort study included 141 women who had undergone conization for cervical dysplasia in 2020 and 2021. Loop size selection was guided by the preoperative colposcopy report and intraoperative diluted Lugol staining. The hemiellipsoid cone volume was compared for subgroups in three categories: patients operated on by residents vs. board-certified gynecologists; patients operated on by female vs. male surgeons; patients who wished to pursue future pregnancy after conization vs. those who did not. RESULTS: Female surgeons excised insignificantly less cervical tissue compared with their male counterparts (p=0.08). In the subgroup of patients without the wish to conceive, male surgeons tended to excise significantly bigger volumes during conization (p=0.008). No significant difference (p=0.74) regarding volume of resected tissue was evidenced when comparing residents to board-certified surgeons, both in patient subgroups with (p=0.58) and without (p=0.36) a wish to conceive. Male surgeons tended to resect higher volumes (p=0.012) if board-certified compared to their board-certified female colleagues. CONCLUSION: There were insignificant differences regarding cone depth and volume or incomplete resection when stratified by operator experience and sex. However, male gynecologists removed significantly larger cone volumes in the subgroup of patients who did not pursue future pregnancy.

Cut-off Analysis of HLA-A and HLA-B/C Expression as a Potential Prognosticator of Favorable Survival in Patients With Metastatic Breast Cancer.

BACKGROUND/AIM: Loss of differentiation of breast cancer cells in association with a down-regulated class I human leukocyte antigen (HLA) expression can lead to proliferation unhampered by cytotoxic T lymphocytes, which has been proven to be of prognostic relevance. The objective of this study was to determine the levels of HLA-A and HLA-B/C expression in metastatic breast cancer (MBC) cells and their usefulness for predicting 5-year survival. MATERIALS AND METHODS: This prospective double-blinded cohort study analyzed patients starting a new line of therapy for MBC. RT-qPCR was used to determine the levels of HLA-A and B/C expression in MBC cells and the mRNA-based tumor intrinsic subtype. Two receiver operating characteristic curves (ROC) were constructed in order to determine whether HLA-A and HLA-B/C expression levels can be used for predicting 5-year survival. Youden J points, and sensitivity and specificity optimized cut-off points were determined for both ROC curves. RESULTS: We enrolled 34 patients. The ROC curve for HLA-B/C had the highest AUC compared to HLA-A (0.55 vs. 0.42). High levels of HLA-A and HLA-B/C expression (40-ΔΔCT of 33.5 and 31.9, respectively) were highly specific (reaching 87.5% for HLA-A and even 100% specificity for HLA-B/C) yet insensitive for five-year survival in our study. CONCLUSION: High expression of certain class I HLA molecule subtypes by MBCs, in particular high HLA-A or B/C expression by MBC cells seems very specific in predicting the 5-year survival. We determined cut-off values for these HLA molecule clusters with high specificity, which might help identify patients with a favorable prognosis as prognosticators of a 5-year overall survival if their sensitivity is improved in larger prospective cohorts.

The association between adverse childhood experiences and peripartal pain experience.

ABSTRACT: Adverse childhood experiences (ACEs) are associated with altered ongoing and evoked pain experiences, which have scarcely been studied for the peripartum period. We aimed to investigate how ACEs affect pain experience in pregnancy and labor. For this noninterventional trial with a short-term follow-up, pregnant women were divided into a trauma group (TG) with ACEs (n = 84) and a control group (CG) without ACEs (n = 107) according to the Childhood Trauma Questionnaire. Pain experience in pregnancy and labor was recorded by self-report and the German Pain Perception Scale. Pain sensitivity prepartum and postpartum was assessed by Quantitative Sensory Testing and a paradigm of conditioned pain modulation (CPM), using pressure pain thresholds (PPTs) and a cold pressor test. The TG showed higher affective and sensory scores for back pain and a more than doubled prevalence of preexisting back pain. Pelvic pain differences were nonsignificant. The TG also exhibited increased affective scores (1.71 ± 0.15 vs 1.33 ± 0.11), but not sensory scores for labor pain during spontaneous delivery. There were no group differences in prepartum pain sensitivity. While PPTs increased through delivery in the CG (clinical CPM), and this PPT change was positively correlated with the experimental CPM ( r = 0.55), this was not the case in the TG. The association of ACEs with increased peripartal pain affect and heightened risk for preexisting back pain suggest that such women deserve special care. The dissociation of impaired clinical CPM in women with ACEs and normal prepartum experimental CPM implies at least partly different mechanisms of these 2 manifestations of endogenous pain controls.

First experiences with a diode laser in major gynecological laparoscopic procedures show lack of benefit and impaired feasibility.

PURPOSE: The aim of this study is to evaluate feasibility and potential benefit of a diode laser in major laparoscopic procedures in gynecology. METHODS: Between 2018 and 2020, a total of 42 cases were enrolled in this study comparing standard electrosurgery with diode laser-supported therapy in laparoscopic supracervical hysterectomy (LASH), total laparoscopic hysterectomy (TLH), or laparoscopic myoma enucleation (LME). Dual wavelength 45 W diode laser light was used to cut and coagulate during laparoscopy in the prospective interventional arm consisting of 11 cases, while 31 matching patients who received conventional treatment with monopolar/bipolar current for the same interventions were retrospectively identified in our laparoscopy database. Recruitment in the prospective interventional laser diode arm was terminated after only 11 patients (instead of planned 50) due to intense hemorrhage and massive smoke development. RESULTS: A total of 42 cases were analyzed (11 LME, 19 LASH, and 12 TLH). Strong smoke development was evident in all 11 cases in the diode laser arm. It was necessary to convert to bipolar or monopolar current in all hysterectomies (n = 9) with initial diode laser implementation due to increased bleeding and smoke development. Conventional current sources had to be used in LMEs (n = 2) due to excessive bleeding and poor visibility during enucleation of the fibroid. A significant difference (p < 0.0001) was observed regarding smoke development when comparing the laser arm with the control arm. CONCLUSION: We found a 45-W diode laser to be inferior to electrosurgical techniques for major laparoscopic gynecologic surgeries regarding bleeding control and smoke development.