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Purpose To limit the burden of long-term immunosuppression (IS) after uterus transplantation (UTx), removal of the uterine allograft is indicated after maximum two pregnancies. Hitherto this has required graft hysterectomy by laparotomy. Our objective was to demonstrate, as a proof of concept, the feasibility of less traumatic transplantectomy by total laparoscopic hysterectomy (TLH). Patient A 37-year-old woman with uterovaginal agenesis due to Mayer–Rokitansky–Küster–Hauser syndrome (MRKHS) who had undergone neovaginoplasty at age 19 years prior to living-donor (LD) UTx in 10/2019 at age 35 years gave birth to a healthy boy by primary cesarean section in 06/2021. During pregnancy, she developed impaired renal function, with bilateral hydronephrosis, necessitating early allograft removal in 09/2021 to prevent chronic kidney disease, particularly during a potential second pregnancy. Methods Transplantectomy by TLH essentially followed standard TLH procedures. We paid meticulous attention to removing as much donor tissue as possible to prevent postoperative complications from residual donor tissue after stopping IS, as well as long-term vascular damage. Results TLH was performed successfully without the need to convert to open surgery. Surgical time was 90 min with minimal blood loss. No major complications occurred intra- or postoperatively and during the subsequent 9-month follow-up period. Kidney function normalized. Conclusions To our knowledge, we report the first successful TLH-based removal of a uterine allograft in a primipara after LD UTx, thus demonstrating the feasibility of TLH in uterus recipients with MRKHS.

BackgroundThe clinical utility of molecular profiling and targeted therapies for neuro-oncology patients outside of clinical trials is not established. We aimed at investigating feasibility and clinical utility of molecular profiling and targeted therapy in adult patients with advanced tumors in the nervous system within a prospective observational study.Methodsmolecular tumor board (MTB)@ZPM (NCT03503149) is a prospective observational precision medicine study for patients with advanced tumors. After inclusion of patients, we performed comprehensive molecular profiling, formulated ranked biomarker-guided therapy recommendations based on consensus by the MTB, and collected prospective clinical outcome data.ResultsHere, we present initial data of 661 adult patients with tumors of the nervous system enrolled by December 31, 2021. Of these, 408 patients were presented at the MTB. Molecular-instructed therapy recommendations could be made in 380/408 (93.1%) cases and were prioritized by evidence levels. Therapies were initiated in 86/380 (22.6%) cases until data cutoff. We observed a progression-free survival ratio >1.3 in 31.3% of patients.ConclusionsOur study supports the clinical utility of biomarker-guided therapies for neuro-oncology patients and indicates clinical benefit in a subset of patients. Our data might inform future clinical trials, translational studies, and even clinical care.

Background ABP 980 is a biosimilar antibody to reference trastuzumab (RTZ). Aim of the following study is to confirm the similarity of ABP 980 and RTZ in terms of clinical efficacy and safety in patients with HER2-positive early breast cancer (EBC) undergoing neoadjuvant trastuzumab-containing chemotherapy in a clinical real-world situation that also includes patients receiving pertuzumab. Methods Patients with HER2-positive EBC, who were treated from 12/2010 to 03/2020 at the Department of Women’s Health at Tuebingen University Hospital, Germany, with at least four cycles of neoadjuvant chemotherapy (+/− pertuzumab) in combination with ABP 980 or RTZ were included in a retrospective analysis. For efficacy analysis patients achieving a pathologic complete remission (pCR = no invasive tumor in breast and lymph nodes) were compared. Safety was evaluated by comparing the number of patients with a decrease in left ventricular function (LVEF) of > 10%. Results 124 patients were included of whom 46 (37.1%) have received ABP 980 and 77 (62.9%) were treated with RTZ. A pCR was found in 77 patients (62.1%). For patients treated with ABP 980 as compared to RTZ, there was no significant difference regarding efficacy (pCR-rates of 60.9% versus 62.8%, p = 0.829) or cardiac safety (LVEF decline in 6.5% versus 2.6%, p = 0.274). Conclusion Similarity of ABP 980 as compared to RTZ was confirmed in a real-world situation, including a large proportion of patients that have also received pertuzumab treatment.

Preterm birth serves as one of the leading causes of neonatal mortality worldwide. The underlying mechanisms that contribute to preterm birth are not yet fully understood. However, an association between periodontitis and preterm birth has been proposed. The periodontal status and presence of periodontal pathogens in women with different birth outcomes have been previously examined. However, varying definitions of periodontitis and different microbiological methods make their interpretation challenging. The aim of this case-control study on women with and without preterm birth was to investigate their periodontal status using the current classification system for periodontal diseases. Moreover, differences in the periodontal microbiome of the study participants were investigated. Therefore, we collected data on oral and periodontal parameters in 77 puerperal women divided into two groups based on gestational age at delivery: 33 patients with preterm birth (PTB, 37 weeks). These data included pocket probing depth (PPD), clinical attachment loss (CAL), bleeding on probing (BOP), gingival-bleeding index, DMFT index, and gynecologic and dental history. In addition, their oral microbiome was explored. Median CAL and percentage PPD ≥ 4 mm were significantly higher in the PTB group than in the TB group (p = 0.0128 and p = 0.047, respectively). Birth weight was significantly higher in periodontally healthy women than in those with gingivitis (p = 0.0078) or periodontitis (p = 0.0127). The periodontal microbiome differed significantly between groups. Our results are underlining the possible association between periodontitis and preterm delivery. Women with periodontitis had babies with significantly lower birth weights. The microbiome varied between the groups.

Preterm birth serves as one of the leading causes of neonatal mortality worldwide. The underlying mechanisms that contribute to preterm birth are not yet fully understood. However, an association between periodontitis and preterm birth has been proposed. The periodontal status and presence of periodontal pathogens in women with different birth outcomes have been previously examined. However, varying definitions of periodontitis and different microbiological methods make their interpretation challenging. The aim of this case-control study on women with and without preterm birth was to investigate their periodontal status using the current classification system for periodontal diseases. Moreover, differences in the periodontal microbiome of the study participants were investigated. Therefore, we collected data on oral and periodontal parameters in 77 puerperal women divided into two groups based on gestational age at delivery: 33 patients with preterm birth (PTB,lt;37 weeks) and 44 patients with term birth (TB,gt;37 weeks). These data included pocket probing depth (PPD), clinical attachment loss (CAL), bleeding on probing (BOP), gingival-bleeding index, DMFT index, and gynecologic and dental history. In addition, their oral microbiome was explored. Median CAL and percentage PPD ≥ 4 mm were significantly higher in the PTB group than in the TB group (

Congenital Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome is a Mullerian-duct anomaly that is characterized by agenesis of the uterus and upper part of the vagina. Uterus remnants of varying sizes can often be found. Although a functional uterus is missing, the existence of endometriosis in this patient group has been described in the literature; however, a histopathological comparison of the characteristics of the endometrium within the uterus remnants versus endometriotic peritoneal lesions in the same patient is lacking. Moreover, the characteristics of endometriotic tissue in patients with MRKH syndrome have not been correlated with those of patients with endometriosis without Mullerian anomaly. Patients who underwent laparoscopic neovagina creation with the removal of uterus remnants and possible resection of endometriotic lesions between 2010 and 2022 at the Department of Women’s health of the University of Tuebingen were included in our study. Uterine remnants and endometriotic tissue were evaluated via histopathology and immunohistochemistry and were compared to endometriotic samples from patients without Mullerian anomaly. Endometriosis was detected in nine MRKH patients; in four patients, endometrial remnants could be sufficiently compared to endometriotic lesions. All samples exhibited increased expression of hormonal receptors. In two patients, Ki67 proliferation index was significantly increased in peritoneal endometriotic lesions compared with the endometrium of the remnants. In contrast, endometrium and endometriotic lesions of endometriosis patients did not exhibit any differences in the Ki67 proliferation index. Our results demonstrate distinctive immunohistochemical variability between uterine remnants and endometriotic lesions in patients with MRKH syndrome compared with patients with endometriosis, indicating a possible explanation model of the yet-unknown etiology of endometriosis. For confirmation, investigation of a broader patient collective is necessary.

[18F]FDG PET/MRI was shown to have limited sensitivity for N-staging in FIGO I/II cervical carcinoma. Therefore, this prospective study aimed to investigate the additional value of multiparametric dual-time-point PET/MRI and to assess potential influencing factors for lymph node metastasis (LNM) detection. A total of 63 patients underwent whole-body dual-time-point [18F]FDG PET/MRI 60 + 90 min p.i., and 251 LN were evaluated visually, quantified multiparametrically, and correlated with histology. Grading of the primary tumor (G2/G3) had a significant impact on visual detection (sens: 8.3%/31%). The best single parameter for LNM detection was SUVavg, however, with a significant loss of discriminatory power in G2 vs. G3 tumors (AUC: 0.673/0.901). The independent predictors SUVavg, ∆SUVpeak, LN sphericity, ADC, and histologic grade were included in the logistic-regression-based malignancy score (MS) for multiparametric analysis. Application of MS enhanced AUCs, especially in G2 tumors (AUC: G2:0.769; G3:0.877) and improved the accuracy for single LNM from 34.5% to 55.5% compared with the best univariate parameter SUVavg. Compared with visual analysis, the use of the malignancy score increased the overall sensitivity from 31.0% to 79.3% (Youden optimum) with a moderate decrease in specificity from 98.3% to 75.6%. These findings indicate that multiparametric evaluation of dual-time-point PET/MRI has the potential to improve accuracy compared with visual interpretation and enables sufficient N-staging also in G2 cervical carcinoma.

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Purpose:[18F]FDG PET/MRI comes with limited sensitivity for initial detection of lymph node metastases (LNM) in early stage cervical carcinoma. Therefore, the aim of this prospective study was to investigate the additional value of multiparametric dual-time-point PET/MRI and to asses potential influencing factors for LNM detection.Methods: 63 patients underwent whole-body dual-time-point [18F]FDG-PET/MRI ≈60+90min p.i. (Biograph mMR®, Siemens Healthineers). 251 LN were evaluated visually by nuclear medicine and radiology expert, quantified multiparametrically and were correlated with histology. Multiparametric analysis was performed using a logistic regression-based malignancy score (MS).Results:Overall prevalence of LNM was 17.1% and dependent on tumor grade (Gx 1/6, G1:0/19, G2:18/106, G3:24/120). Grading of the primary tumor (G2/G3) had a significant impact on visual detection (sens: 8.3%/31%).Best single parameter for LNM detection was SUVavg, however with a significant loss of discriminatory power in G2 vs. G3 tumors (AUC: 0.673/ 0.901). For multiparametric analysis, the independent predictors “SUVavg, ∆SUVpeak (60 to 90 min p.i.), LN sphericity, ADC and histologic grade” were included in the MS. Application of the MS enhanced AUCs especially in G2 tumors (AUC: G2:0.769; G3:0.877) and improved accuracy for single LNM from 34.5% to 55.5% compared to the best univariate parameter SUVavg.Equated to the expert consensus, use of the malignancy score increased overall sensitivity from 31.0% to 79.3% (Youden optimum) with a moderate decrease in specificity from 98.3% to 75.6%.Conclusion:Low histologic grad (G2 vs. G3) hampers visual detectability of LNM in [18F]FDG-PET/MRI. Multiparametric evaluation of dual-time-point PET/MRI has the potential to improve accuracy compared to visual interpretation and enables sufficient N-staging also in G2 tumors.Trial registration:DRKS00014346. Registered April 4, 2018 - retrospectively registered,https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00014346

Purpose Surgery and radiotherapy as part of breast cancer treatment can lead to lymphoedema of the upper extremities (breast cancer-related lymphoedema = BCRL) and reduce the quality of life (health-related quality of life = HRQoL). The aim of the present study was to investigate the influence of paddling in a dragon boat (PP), on HRQoL and BCRL in breast cancer survivors (BCS). Methods Between April and October 2017, a prospective case-control study evaluated the effects of PP compared to a control group. In the paddle group (n = 28), weekly arm circumference measurements were taken at four defined anatomic areas of the arm before and after training; in the control group (n = 70) the measurements were taken once a month. At the beginning and end of the study, questionnaires from both groups (SF 36, EORTC QLQ-C30) were evaluated to understand the differences in HRQoL. Results The paddle group started with a higher HRQoL compared to in the control group. Most interesting, whether the affected or unaffected arm, whether before or after training - the arm circumference decreased over time in the paddling group. A pre-existing lymphoedema was not negatively influenced by paddling. In the paddle group the physical health was constant over the season, while the physical health of the control group decreased significantly over time. Conclusion PP in a dragon boat does not lead to the development or worsening of pre-existing lymphoedema due to breast cancer therapy and seems to have a positive effect on the quality of life.

Preclinical data suggest that neoadjuvant chemotherapy (NAT) may promote micrometastatic spread. We aimed to compare the detection rate and prognostic relevance of disseminated tumor cells (DTCs) from the bone marrow (BM) of patients with early-stage breast cancer (EBC) after NAT with that of therapy-naive EBC patients. DTCs were identified from BM samples, collected during primary surgery. Patients who received NAT were compared to patients who received chemotherapy after surgery. In total, 809 patients were analyzed. After NAT, 45.4% of patients were DTC-positive as compared to 19.9% of patients in the adjuvant chemotherapy group (p < 0.001). When sampled in patients who had undergone NAT, the detection of DTCs in the BM was significantly increased (OR: 3.1; 95% confidence interval (CI): 2.1–4.4; p < 0.001). After NAT, DTC-positive patients with ≥2 DTCs per 1.5 × 106 mononuclear cells in their BM had an impaired disease-free survival (HR: 4.8, 95% CI: 0.9–26.6; p = 0.050) and overall survival (HR: 4.2; 95% CI: 1.4–12.7; p = 0.005). The higher rate of DTC-positive patients after NAT as compared to a treatment-naive comparable control cohort suggests that NAT supports tumor cell dissemination into the bone marrow. DTC positivity in BM predicted relapse in various distant organs, implying that tumor cell dissemination was not restricted to the bone marrow.

Preclinical data suggest that neoadjuvant chemotherapy (NAT) may promote micrometastatic spread. We aimed to compare the detection rate and prognostic relevance of disseminated tumor cells (DTCs) from the bone marrow (BM) of patients with early-stage breast cancer (EBC) after NAT with that of therapy-naive EBC patients. DTCs were identified from BM samples, collected during primary surgery. Patients who received NAT were compared to patients who received chemotherapy after surgery. In total, 809 patients were analyzed. After NAT, 45.4% of patients were DTC-positive as compared to 19.9% of patients in the adjuvant chemotherapy group (p < 0.001). When sampled in patients who had undergone NAT, the detection of DTCs in the BM was significantly increased (OR: 3.1; 95% confidence interval (CI): 2.1–4.4; p < 0.001). After NAT, DTC-positive patients with ≥2 DTCs per 1.5 × 106 mononuclear cells in their BM had an impaired disease-free survival (HR: 4.8, 95% CI: 0.9–26.6; p = 0.050) and overall survival (HR: 4.2; 95% CI: 1.4–12.7; p = 0.005). The higher rate of DTC-positive patients after NAT as compared to a treatment-naive comparable control cohort suggests that NAT supports tumor cell dissemination into the bone marrow. DTC positivity in BM predicted relapse in various distant organs, implying that tumor cell dissemination was not restricted to the bone marrow.

Lymph node metastasis (LNM) is present in a minority of patients with early stages of cervical carcinomas. As conventional imaging including PET/CT has shown limited sensitivity, systematic lymphadenectomies are often conducted for staging purposes. Therefore, the aim of this prospective study was to analyze the impact of (18)F-FDG PET/MRI in addition to sentinel lymph node (SLN) biopsy on lymph node (LN) status. Methods: Forty-two women with an initial diagnosis of Fédération Internationale de Gynécologie et d’Obstétrique (FIGO) IA–IIB cervical carcinoma were included between March 2016 and April 2019. Each patient underwent preoperative whole-body (18)F-FDG PET/MRI and SLN imaging with SPECT/CT after intracervical injection of (99m)Tc-labeled nanocolloid. Systematic lymphadenectomy and SLN biopsy served as the reference standard. Staging using PET/MRI was performed by nuclear medicine and radiology experts working in consensus. Results: One patient was excluded from surgical staging because of liver metastases newly diagnosed on PET/MRI. The overall prevalence of LNM in the remaining 41 patients was 29.3% (12/41). Five of 12 patients with LNM had solely small metastases with a maximum diameter of 5 mm. The consensus interpretation showed PET/MRI to have a specificity of 100% (29/29; 95% CI, 88.3%–100%) for LNM staging but a low sensitivity, 33.3% (4/12; 95% CI, 12.8%–60.9%). LN size was the most important factor for the detectability of metastases, since only LNMs larger than 5 mm could be identified by PET/MRI (sensitivity, 57.1% for >5 mm and 0% for ≤5 mm). Paraaortic LNM was evaluated accurately in 3 of the 4 patients with paraaortic LN metastasis. SLNs were detectable by SPECT/CT in 82.9% of the patients or 69.0% of the hemipelves. In cases with an undetectable SLN on SPECT/CT, the malignancy rate was considerably higher (31.2% vs. 19.3%). The combination of PET/MRI and SLN SPECT/CT improved the detection of pelvic LNM from 33.3% to 75%. Conclusion: (18)F-FDG PET/MRI is a highly specific N-staging method and improves LNM detection. Because of the limited sensitivity in frequently occurring small LNMs, PET/MRI should be combined with SLN mapping. The proposed combined protocol helps to decide whether extensive surgical staging is necessary in patients with FIGO I/II cervical cancer.

BACKGROUND One in eight women is diagnosed with breast cancer in the course of their life. As systematic palliative treatment has only a limited effect on survival rates, the concept of health-related quality of life (HRQoL) was developed for measurement of patient-centered outcomes. Various studies have already demonstrated the reliability of paper-based patient-reported outcome (pPRO) and electronic patient-reported outcome (ePRO) surveys and that the 2 means of assessment are equally valid. OBJECTIVE The aim of this study was to analyze the acceptance and evaluation of a tablet-based ePRO app for breast cancer patients and to examine its suitability, effort, and difficulty in the context of HRQoL and sociodemographic factors. METHODS Overall, 106 women with adjuvant or advanced breast cancer were included in a 2-center study at 2 major university hospitals in Germany. Patients were asked to answer HRQoL and PRO questionnaires both on a tablet on-site using a specific eHealth assessment website and on paper. The suitability, effort, and difficulty of the app and self-reported technical skills were also assessed. Only the results of the electronically acquired data are presented here. The results of the reliability of the pPRO data have already been published elsewhere. RESULTS Patients regarded the ePRO assessment as more suitable (80/106, 75.5%), less stressful (73/106, 68.9%), and less difficult (69/106, 65.1%) than pPRO. The majority of patients stated that ePRO assessment improves health care in hospitals (87/106, 82.1%). However, evaluation of ePROs depended on the level of education (P=.003) in the dimensions of effort and difficulty (regression analysis). The app was rated highly in all categories. HRQoL data and therapy setting did not show significant correlations with the app’s evaluation parameters. CONCLUSIONS The results indicate that ePRO surveys are feasible for measuring HRQoL in breast cancer patients and that those patients prefer ePRO assessment to pPRO assessment. It can also be seen that patients consider ePRO assessment to improve hospital health care. However, studies with larger numbers of patients are needed to develop apps that address the needs of patients with lower levels of education and technical skills.

Background The Mayer-Rokitansky-Küster-Hauser syndrome, MRKHS, is a rare (orphan) disease characterized by the aplasia or hypoplasia of the uterus and the vagina. In women's health research, little is known as to how much care provision for patients with MRKHS takes into account their socio-demographic together with their clinical characteristics. This work examines the patients’ socio-demographic characteristics, highlighting issues of inappropriate and deficient provision of care. Methods The study was carried out as part of the larger TransCareO project and included a group of N=129 MRKHS patients who underwent surgery between 2008 and 2012. Using a specially developed questionnaire, we analyzed MRKHS patients’ data found both in the clinical documentation of the Department for Women's Health, University Hospital of Tübingen and the patient surveys of the Center for Rare Genital Malformations (CRGM/ ZSGF). Patients who took part in interviews were compared with non-respondents. Results Patient respondents and non-respondents did not differ as to the parameters of interest. In most cases, primary amenorrhea was reported as an admission reason. In 24% of patients, a medical intervention (hymenal incision or hormone treatment) already occurred before admission to the Center in Tübingen and proper diagnosis of MRKHS. About one third received in advance inappropriate treatment. During the therapy, more than half of the patients were in a solid partnership. 10% of the family anamneses documented the occurrence of urogenital malformations. Conclusions Care provision for MRKHS patients is largely characterized by delayed proper diagnosis and in part, by inappropriate treatment attempts; there are also indications of regional differences. Anamnestic clues such as an asymptomatic amenorrhea or renal abnormalities of unclear origin still fail to result early enough in referral to a center on the basis of suspected MRKHS diagnosis. Urogenital malformations in the family are more common in patients than in the general population. For patients, a wide range of burdens are associated with the diagnosis. Abnormalities compared to their female peers occur, for instance, in the partnership status: MRKHS patients have more rarely a partner.

BACKGROUND Over the last decade, a growing body of studies regarding the application of eHealth and various digital interventions has been published and are widely used in the psycho-oncological care. However, the effectiveness of eHealth applications in psycho-oncological care is still questioned due to missing considerations regarding evidence-based studies on the demands and needs in cancer-affected patients. OBJECTIVE This cross-sectional study aimed to explore the cancer-affected women’s needs and wishes for psycho-oncological content topics in eHealth applications and whether women with cancer differ in their content topics and eHealth preferences regarding their experienced psychological burden. METHODS Patients were recruited via an electronic online survey through social media, special patient Internet platforms, and patient networks (both inpatients and outpatients, University Hospital Tuebingen, Germany). Participant demographics, preferences for eHealth and psycho-oncological content topics, and their experienced psychological burden of distress, quality of life, and need for psychosocial support were evaluated. RESULTS Of the 1172 patients who responded, 716 were included in the study. The highest preference for psycho-oncological content topics reached anxiety, ability to cope, quality of life, depressive feelings, and adjustment toward a new life situation. eHealth applications such as Web-based applications, websites, blogs, info email, and consultation hotline were considered to be suitable to convey these content topics. Psychological burden did not influence the preference rates according to psycho-oncological content and eHealth applications. CONCLUSIONS Psycho-oncological eHealth applications may be very beneficial for women with cancer, especially when they address psycho-oncological content topics like anxiety, ability to cope, depressive feelings, self-esteem, or adjustment to a new life situation. The findings of this study indicate that psycho-oncological eHealth applications are a promising medium to improve the psychosocial care and enhance individual disease management and engagement among women with cancer.