Stable expansion of high-grade serous ovarian cancer organoids requires a low-Wnt environment.

High-grade serous ovarian cancer (HGSOC) likely originates from the fallopian tube (FT) epithelium. Here, we established 15 organoid lines from HGSOC primary tumor deposits that closely match the mutational profile and phenotype of the parental tumor. We found that Wnt pathway activation leads to growth arrest of these cancer organoids. Moreover, active BMP signaling is almost always required for the generation of HGSOC organoids, while healthy fallopian tube organoids depend on BMP suppression by Noggin. Fallopian tube organoids modified by stable shRNA knockdown of p53, PTEN, and retinoblastoma protein (RB) also require a low-Wnt environment for long-term growth, while fallopian tube organoid medium triggers growth arrest. Thus, early changes in the stem cell niche environment are needed to support outgrowth of these genetically altered cells. Indeed, comparative analysis of gene expression pattern and phenotypes of normal vs. loss-of-function organoids confirmed that depletion of tumor suppressors triggers changes in the regulation of stemness and differentiation.

Prospective Randomized Study on the Use of Robot-Assisted Postoperative Visits.

Introduction: Robot-assisted visits, as part of telemedicine, can offer doctors the opportunity to take care of patients. Due to the COVID-19 pandemic, there has been an increase in telemedicine. The use of teleconsultations, for example, has found its way into the German health care system. However, the practicability and the benefit of robot-assisted postoperative visits have not been systematically investigated in any study worldwide. Methods: Patients were enrolled in a prospective randomized study comparing the standard postoperative visit with the doctor on call and the digital visit through the Double robot between December 2019 and April 2022. All patients and doctors completed a survey after the visit. The primary outcome was patient satisfaction. Secondary outcomes included patients' pain, hospitalization time, and patients' opinions about the usefulness of the robot. Likert scales of arithmetic mean, standard deviation, and subgroup analyses with the Mann-Whitney U test and the Fisher's exact test were used to compare outcomes. Results: We enrolled a total of 106 patients: 54 (50.9%) of them underwent the robot visit and 52 (49.1%) underwent the conventional visit. Baseline demographic and clinical characteristics were similar between groups. Our primary outcome was the same in both arms. Similar results were obtained for the secondary endpoints. Conclusion: Robot-televisits were comparable with standard visits including satisfaction, usefulness, and time of hospitalization. Digitalization in medicine is an irreversible process, especially after the COVID-19 pandemic. We hope that our study will provide concrete help to encourage the allocation of funds for telemedicine in Germany's health care system.

HE4 as a serum biomarker for the diagnosis of pelvic masses: a prospective, multicenter study in 965 patients.

BACKGROUND: To evaluate the diagnostic value of adding human epididymis protein 4 (HE4), cancer antigen 125 (CA125) and risk of malignancy algorithm (ROMA) to ultrasound for detecting ovarian cancer in patients with a pelvic mass. METHODS: This was a prospective, observational, multicenter study. Patients aged > 18 years who were scheduled to undergo surgery for a suspicious pelvic mass had CA125 and HE4 levels measured prior to surgery, in addition to a routine transvaginal ultrasound scan. The diagnostic performance of CA125, HE4 and ROMA for distinguishing between benign and malignant adnexal masses was assessed using receiver operating characteristic (ROC) analysis and the corresponding area under the curve (AUC). RESULTS: Of 965 evaluable patients, 804 were diagnosed with benign tumors and 161 were diagnosed with ovarian cancer. In late-stage ovarian cancer, CA125, HE4 and ROMA all had an excellent diagnostic performance (AUC > 0.92), whereas in stage I and II, diagnostic performance of all three biomarkers was less adequate (AUC < 0.77). In the differential diagnosis of ovarian cancer and endometriosis, ROMA and HE4 performed better than CA125 with 99 and 98.1% versus 75.0% sensitivity, respectively, at 75.4% specificity. CONCLUSIONS: ROMA and HE4 could be valuable biomarkers to help with the diagnosis of ovarian cancer in premenopausal patients in order to differentiate from endometriosis, whereas CA125 may be more adequate for postmenopausal patients.

Closure of the cervical os in patients after fertility preserving treatment for early cervical cancer - results of a prospective observational study.

INTRODUCTION: Up to 50% of the infants delivered after radical vaginal trachelectomy (RVT) are born prematurely. An effective strategy to reduce this number could be the closure of the cervical os (CCO). PATIENTS AND METHODS: Fifteen pregnant patients who had a RVT due to early cervical cancer were included in this prospective case control study. All patients were scheduled for CCO early in the second trimester. CCO was performed in 12 patients. Their data were compared to data from 125 pregnancies after a RVT without CCO. RESULTS: The patients who had CCO were compared to patients without CCO. One patient had an early rupture of the amniotic membranes prior to CCO. Two patients chose not to undergo CCO. In 12 patients CCO was performed without complications. There was no early preterm delivery in the CCO group as compared to a rate of 5% in 125 pregnancies in the non-CCO group. DISCUSSION: We developed a protocol to reduce the risk of preterm deliveries after a RVT. Digital examinations should be avoided. Vaginal checks for pH can discover ascending infections - the main cause of preterm deliveries after a RVT. Infections should be treated adequately. CCO can further reduce the risk of preterm deliveries after a RVT.

Follow-up after radical vaginal trachelectomy (RVT): patients' problems and physicians' difficulties.

PURPOSE: Patients after radical vaginal trachelectomy (RVT) need specific follow-up treatment because their problems differ from those of other gyneco-oncologic patients. Anatomic changes after surgery complicate examinations. Recognition and treatment of these issues require physician's expertise. PATIENTS AND METHODS: We evaluated the follow-up data of 70 patients who underwent RVT for early cervical cancer between 03/2010 and 12/2013. The follow-up interval in the first 2 years was 3 and 6 months in the following 2 years. We used a tailored protocol to describe the special problems after RVT. RESULTS: Cervical stenosis was one of the central problems independent of time interval to RVT. Physicians' most significant problem was to locate the exact position of the neo-cervix and thus to receive valid pap smears. CONCLUSIONS: Follow-up of patients after RVT needs special expertise because the symptoms differ from those after hysterectomy and examinations ensuring oncologic safety require special attention.

European Society of Gynecological Oncology Task Force for Fertility Preservation: Clinical Recommendations for Fertility-Sparing Management in Young Endometrial Cancer Patients.

Endometrial cancer (EC) in young women of reproductive age is a relatively rare diagnosis. However, since in the modern era women delay their childbearing for a variety of social reasons, more and more women in the near future will be nulliparous and have a diagnosis of EC at the same time. Hence, a more conservative approach of EC is desirable to preserve fertility of these women, without compromising their survival. Recently, the number of studies reporting encouraging results on fertility-sparing management of EC with high dose of progestins is increasing. It seems that preserving the uterus and the ovaries in a carefully selected patient with EC confers only a very small risk combined with an enormous benefit. Selection of women suitable for such a conservative approach, as well as method of treatment, follow-up, recurrence, obstetric outcomes, and survival rates are very important parameters when consulting women with EC wishing to preserve their fertility. In this article, we try to elucidate all the previously mentioned aspects and formulate clinical recommendations, based on published data, about the most proper approach and consultation of these patients.

The efficacy of short-term psycho-oncological interventions for women with gynaecological cancer: a randomized study.

OBJECTIVES: We aimed to examine the efficacy of two psycho-oncological interventions in anxiety, depression, and self-perceived as well as physiological stress in inpatients with gynaecological cancer. METHODS: Forty-five women were included in the trial. Thirty-five were categorized as being at high risk of anxiety and depression, and were randomized to either a single psycho-oncological therapy session or a single-session relaxation intervention. RESULTS: A significant decrease in anxiety [mean (t0) = 12, mean (t1) = 7.47, p = 0.001] and depression [mean (t0) = 9.71, mean (t1) = 6.35, p < 0.001] was observed in the psycho-oncological intervention group. In the relaxation group, anxiety also significantly decreased [mean (t0) = 11.67, mean (t1) = 8.22, p = 0.003], whereas depression did not. A comparative analysis of both interventions showed a trend in favour of psycho-oncological therapy for the treatment of depression (F = 3.3, p = 0.078). However, self-reported stress (p = 0.031) and different objective stress parameters only significantly decreased in the relaxation group. CONCLUSIONS: Psycho-oncological interventions should represent an essential part of interdisciplinary care for gynaecological cancer patients. Both types of intervention may reduce anxiety. However, the single psycho-oncological therapy session might be slightly more effective in treating depression, whereas the single-session relaxation intervention seems to have a stronger effect on physiological stress parameters.

Pattern of cancer recurrence in 320 patients after radical vaginal trachelectomy.

OBJECTIVE: The oncological outcome regarding disease-free survival and overall survival after radical vaginal trachelectomy (RVT) is the same as the rates after radical hysterectomy. We aim to analyze predictive and risk factors and death in patients with cervical cancer undergoing fertility preservation by laparoscopic lymphadenectomy and RVT. METHODS: Three hundred twenty patients with cervical cancer underwent RVT between March 1995 and February 2013. In our study, we examined recurrence rates analyzed by risk factors. We classified the presence of lymphovascular space invasion, depth of tumor infiltration, tumor size, and tumor grading as risk factors. The mean follow-up time was 48 months. RESULTS: Ten of the 320 patients had cancer recurrence. Recurrence appeared at a mean time of 26.1 months (3-108 months) after RVT. Five patients died within 8.8 months (4-15 months) after recurrence was diagnosed. Two of these 5 patients had distant metastasis at the time of recurrence. Five patients were treated successfully by surgery, and 4 patients were treated successfully by chemotherapy. The mean follow-up after the recurrence of these 5 patients is 76 months (6-120 months). None of the 10 patients with recurrences in our series showed significant high-risk factors. CONCLUSION: There seems to be no pattern in the recurrence of cancer after RVT. It is strictly mandatory to follow up the patients closely every 3 months after RVT to diagnose recurrence at an early stage so therapeutic options such as chemoradiation are still available. Once distant metastasis occurs, prognosis is not good.

Laparoscopic pelvic lymphadenectomy in 32 pregnant patients with cervical cancer: rationale, description of the technique, and outcome.

OBJECTIVE: Individualized treatment of pregnant patients with cervical cancer is mandatory; hence, information on nodal status is pivotal to allow a waiting strategy in early-stage disease.We aimed to verify the oncological safety and surgical reproducibility of a standardized laparoscopic pelvic lymphadenectomy in pregnant patients with cervical cancer. METHODS: We standardized laparoscopic pelvic lymphadenectomy during the first and second term of gestation in 32 patients with cervical cancer since 1999. According to gestational week (GW) of less than 16 GWs or more than 16 GWs, 2 different techniques were used. RESULTS: The International Federation of Gynecology and Obstetrics stages were IA in 10 patients, IB1 in 17 patients, IB2 in 4 patients, and IIA in 1 patient. Mean (SD) GW was 17.5 (5.1) weeks. Mean (SD) operative time was 105.4 (29) minutes. Mean (SD) blood loss was 5.3 (10.2) mL. There were no conversion to laparotomy and no intraoperative complications. A median number of 14 pelvic lymph nodes (range, 8-57) were harvested. Median hospital stay was 6 days. Median follow-up is 42.5 months (range, 17-164). Four patients had lymph node metastases. Five patients interrupted their pregnancy. Fourteen patients were given neoadjuvant platin-based systemic therapy. All patients are alive and disease free. All children born through cesarean delivery at a mean (SD) 34 (1.9) GWs are well and show normal clinical neurological development. CONCLUSIONS: To the best of our knowledge, this is the largest series so far reported on laparoscopic pelvic lymphadenectomy during pregnancy. This procedure is safe and associated with good oncological and obstetrical outcomes.

Radical vaginal trachelectomy after laparoscopic staging and neoadjuvant chemotherapy in women with early-stage cervical cancer over 2 cm: oncologic, fertility, and neonatal outcome in a series of 20 patients.

OBJECTIVES: The aim of the study was to assess oncologic and fertility outcome of treatment in patients with cervical cancer of more than 2 cm seeking parenthood. METHODS: The regimen consisted of laparoscopic lymphadenectomy as a staging procedure to confirm no lymph node metastases before neoadjuvant chemotherapy (NACT) consisting of 2 or 3 cycles of paclitaxel/ifosfamide/cisplatin followed by radical vaginal trachelectomy (RVT). Oncologic and fertility outcome was evaluated prospectively. RESULTS: Twenty women were enrolled up to now. The mean age was 32 years (range, 26-41 years), and mean tumor size was 3 cm (range, 2.1-5.0 cm). Lymphadenectomy was performed before NACT without complications. During NACT, hematologic toxicity grade 3 was observed in 2 of 20 patients, and renal toxicity grade 3 in 1 of 20 patients. Radical vaginal trachelectomy was performed in 18 women until now with 2 intraoperative complications (ureter injury and injury of internal iliac vein). There were no severe postoperative or long-term complications. Complete pathologic remission was found in 9 of 18 patients. In 2 of 18 patients, chemoradiation was recommended because of insufficient pathologic response in the RVT specimen. After a mean follow-up of 23 months (range, 1-88 months), 1 relapse was observed. After RVT, 7 women tried to conceive until now. Seven pregnancies occurred in 5 women. Four children were born, 2 of whom were premature (31 weeks 2 days and 33 weeks 4 days of gestation); 1 pregnancy is ongoing. CONCLUSIONS: Laparoscopic lymphadenectomy followed by NACT and RVT in pN0 patients with cervical cancer of more than 2 cm seems to be an oncologically safe procedure with promising fertility outcomes.

Vaginal-assisted laparoscopic radical hysterectomy (VALRH) versus laparoscopic-assisted radical vaginal hysterectomy (LARVH) in the treatment of cervical cancer: surgical results and oncologic outcome.

PURPOSE: The aim of this study was to compare the morbidity and survival rates of patients with early-stage cervical cancer treated by vaginal-assisted laparoscopic radical hysterectomy (VALRH) with pair-matched laparoscopic-assisted vaginal radical hysterectomy (LARVH) controls. METHODS: One hundred nine patients who underwent VALRH for cervical cancer stage FIGO Ia1, L1 to IIb between 2007 and 2009 and 200 patients who underwent LARVH between 1994 and 2002 were analysed in their entirety and in a group of matched pairs. RESULTS: In both groups, there was no conversion to laparotomy due to an intraoperative complication. Prevalence of blood transfusions was significantly lower in the VALRH group (2 vs. 39 patients; P < 0.001). Bladder function resumed sooner (P < 0.001), and patients were discharged earlier after VALRH (P < 0.001). There were no intraoperative injuries in the VALRH group. In the LARVH group, the most common intraoperative injury occurred to the bladder (7.0 %). Postoperatively, the most common complication in the VALRH group was ureterovaginal fistula (2.7 %) and fever (2.7 %) and in the LARVH ureterostenosis (3.5 %), uretero/bladder fistula (1 %), and fever (7 %). For patients with tumour stage Ib1 the 5-year recurrence-free survival was 92.8 % and 5-year overall survival 95.2 % following VALRH and 88.2 and 90.5 %, respectively, following LARVH. No significant difference in the survival rate was found (log rank, P = 0.740). CONCLUSION: VALRH is a feasible and oncologically safe surgical option for patients with early-stage cervical cancer. We believe the complication rate is lowered in VALRH by the combination of the laparoscopic and vaginal approach.

Nausea and Vomiting of Pregnancy and its Management with the Dual-Release Formulation of Doxylamine and Pyridoxine.

Nausea and vomiting of pregnancy (NVP) is among the most common conditions that pregnant women encounter in the early stages of pregnancy. It can affect up to 85% of pregnant women, thus representing a significant public health concern. NVP results in substantial negative physical, emotional, and financial consequences. Despite its prevalence, the pathogenesis remains elusive. Few guidelines have been published; however, several interventions exist for the symptomatic treatment of NVP. The aim of this review is to provide an overview of modern treatment strategies of NVP with a special focus on the recently approved dual-release formulation of the doxylamine and pyridoxine combination. This combination was approved by the Food and Drug Administration (FDA) in November 2016 for the treatment of NVP when conservative management fails, and it has been introduced to the American market in April 2018. The maximum plasma concentration (T max ) of doxylamine and pyridoxal-5-phosphate is reached 3.5 h and 15 h, respectively, after administration of one tablet twice daily, or 4.5 h and 0.5 h, respectively, when one tablet is administered just once daily. In addition, the delayed-release combination allows sufficient levels of doxylamine and the active metabolite pyridoxal-5-phosphate in the systemic circulation, providing symptoms relief in the subsequent morning. Hence, the dual-release formulation can improve the quality of life of pregnant women suffering from NVP. Additionally, large epidemiological trials have shown no increased risk of adverse effects to newborns, demonstrating that its use is not teratogenic.

Value of diagnostic procedures in rectovaginal endometriosis.

OBJECTIVE: Rectovaginal endometriosis has the potential to infiltrate into the rectal wall. The recognition of infiltration prior to surgery is of utmost importance since only infiltrative disease should be treated by partial or complete rectal resection. This study compares different imaging procedures in rectovaginal endometriosis cases in an everyday clinical setting. METHODS: Seventy nine consecutive women diagnosed with rectovaginal endometriosis were included in this prospective study. Preoperatively, all women had a rectovaginal gynaecological examination and transvaginal sonography. Furthermore, MRI or rectal endosonography imaging procedures together with a rectosigmoidoscopy and estimation of a serum Ca125 were undertaken. Sensitivity and specificity of all diagnostic tools were compared with the intraoperative findings. RESULTS: The procedure with the highest accuracy was bimanual rectovaginal gynaecological examination (sensitivity: 0.92/specificity: 0.32). Rectal endosonography obtained a sensitivity of 0.44 and a specificity of 0.77. All other diagnostic procedures such as Ca125 (sensitivity: 0.42/specificity: 0.81), MRI (sensitivity: 0.41/specificity: 0.83), transvaginal sonography (sensitivity: 0.2/ specificity: 0.79) and rectosigmoidoscopy (sensitivity: 0.03/specificity: 0.92) were only of limited value. CONCLUSION: The diagnostic method with the highest sensitivity to detect bowel infiltration in an everyday clinical setting is the gynaecological examination. It is followed by rectal endosonography. However, none of the currently available preoperative diagnostic tools can predict infiltrative growth of rectovaginal endometriosis with any certainty. Hence, infiltrative growth still needs to be verified by operative assessment.

Female physician and pregnancy- effect of the amended German maternity protection act on female doctors' careers.

Objectives: In Germany, the 2018 amended Maternity Protection Act frequently leads to fundamental restrictions for female physicians, especially surgeons, and now even also for students impeding the progress of their careers. Our goal was to assess the current situation for pregnant female physicians and students, respectively, and their perspective on this amendment regarding their career path. Methods: A nationwide survey was conducted in Germany from December 2020 to February 2021. The questionnaire included 790 female physicians and students who were pregnant after the inception of the amended Act. Those women pregnant after the beginning of the corona pandemic were excluded. Results: The survey revealed that two thirds of female physicians worked a maximum of 50% in their previous professional activity as soon as they reported pregnancy. Amongst medical students this amounted up to 72%. 18% of the female physicians and 17% of the female medical students respectively could not follow the sense of these restrictions. 44% of female medical physicians and 33% of female students felt their career impeded. This led up to 43% amongst female medical doctors and 53% amongst female medical students, respectively, who were concerned to announce their pregnancy. As a consequence, pregnancies were reported at 12 weeks in female physicians compared to 19 weeks in medical students. Conclusions: Analyses of the current survey revealed that a relevant number of female physicians and medical students felt impeded in their career path through the application of the amended Maternity Act.

γδ T cell-mediated cytotoxicity against patient-derived healthy and cancer cervical organoids.

Cervical cancer is a leading cause of death among women globally, primarily driven by high-risk papillomaviruses. However, the effectiveness of chemotherapy is limited, underscoring the potential of personalized immunotherapies. Patient-derived organoids, which possess cellular heterogeneity, proper epithelial architecture and functionality, and long-term propagation capabilities offer a promising platform for developing viable strategies. In addition to αß T cells and natural killer (NK) cells, γδ T cells represent an immune cell population with significant therapeutic potential against both hematologic and solid tumours. To evaluate the efficacy of γδ T cells in cervical cancer treatment, we generated patient-derived healthy and cancer ectocervical organoids. Furthermore, we examined transformed healthy organoids, expressing HPV16 oncogenes E6 and E7. We analysed the effector function of in vitro expanded γδ T cells upon co-culture with organoids. Our findings demonstrated that healthy cervical organoids were less susceptible to γδ T cell-mediated cytotoxicity compared to HPV-transformed organoids and cancerous organoids. To identify the underlying pathways involved in this observed cytotoxicity, we performed bulk-RNA sequencing on the organoid lines, revealing differences in DNA-damage and cell cycle checkpoint pathways, as well as transcription of potential γδ T cell ligands. We validated these results using immunoblotting and flow cytometry. We also demonstrated the involvement of BTN3A1 and BTN2A1, crucial molecules for γδ T cell activation, as well as differential expression of PDL1/CD274 in cancer, E6/E7+ and healthy organoids. Interestingly, we observed a significant reduction in cytotoxicity upon blocking MSH2, a protein involved in DNA mismatch-repair. In summary, we established a co-culture system of γδ T cells with cervical cancer organoids, providing a novel in vitro model to optimize innovative patient-specific immunotherapies for cervical cancer.

Laparoscopic lymph node dissection should be performed before fertility preserving treatment of patients with cervical cancer.

OBJECTIVE: The aim of this study is to assess our results of treatment of women with stage I cervical cancer>2 cm in diameter seeking fertility preservation. Treatment consisted of Laparoscopic Pelvic and Paraaortic Lymphadenectomy (LPPLND), and when no nodal metastasis was detected, neoadjuvant chemotherapy (NACT) followed by radical vaginal trachelectomy (RVT). Patients with positive lymph nodes underwent primary chemoradiation. METHODS: A cohort of women younger than 40 years of age with stage I disease>2 cm who underwent LPPLND and either NACT and RVT or chemoradiation. Oncological outcome was evaluated prospectively. RESULTS: Eighteen women were eligible for this study. Twelve (67%) women were diagnosed with metastasis in one or more pelvic and/or paraaortic lymph nodes, and thus received primary chemoradiation. After a mean follow-up of 25.5 months, three out of these 12 women (25%) developed a recurrence. Six women (33%) underwent NACT and RVT. Three patients experienced complete response to NACT and three patients showed more than 50% tumor size reduction. After a mean follow-up of 30.6 months all six women are free of recurrence. One patient delivered a healthy infant. CONCLUSIONS: Staging LPPLND allows separating patients in high or low recurrence risk groups. NACT and RVT seem to be safe for women with completely staged stage I cervical cancer>2 cm in diameter, whereas even after primary chemoradiation, patients with positive lymph nodes experienced recurrence. Therefore, selection of patients with stage I cervical carcinoma>2 cm, eligible for fertility preservation should include histopathologic evaluation of lymph node status before any further treatment.

Neonatal outcome in infants of patients with radical vaginal trachelectomy.

OBJECTIVE: Radical vaginal trachelectomy (RVT) as a fertility-preserving surgery in patients with early-stage cervical cancer is proven to be oncologically safe. After RVT, pregnancy rates vary between 40 % and 80 %. Outcome of infants is complicated by a preterm delivery rate of 30 ­ 50 %. We investigated pregnancy and neonatal outcome after RVT. METHODS: A total of 154 patients with cervical cancer underwent RVT between March 1995 and February 2008. Desire to conceive, pregnancy data, and neonatal outcome were prospectively recorded. Infants' data were pair-matched to data of a control group according to weeks of gestation. Bayley scales of infant development scores were recorded in the group of preterm-delivered infants. RESULTS: Fifty-five women who underwent RVT gave birth to 58 children. Twenty-five (43 %) pregnancies were complicated by preterm rupture of membranes. Thirty infants (52 %) were born preterm, of with 17 (29 %) were < 32 gestational weeks (GW) and seven (12 %) were < 28 GW. There were significantly more premature rupture of membranes in pregnancies after RVT. Despite a higher occurrence of postnatal infections in newborns of mothers who underwent RVT, long-term outcomes are not affected negatively. Regarding overall morbidity, a trend to fewer postnatal complications, compared with the control group, was found. CONCLUSION: Postnatal morbidity in infants of women who underwent RVT, based on trend, is decreased compared with controls. Intense medical observation and treatment during pregnancy, birth, and neonatal period may explain this finding. Neonates in the RVT group have a non-significantly elevated risk for postnatal infections. They do not show an additional risk due to the maternal operation. Their long-term postnatal outcome is not affected negatively.

Volatile organic compounds (VOCs) in exhaled breath of patients with breast cancer in a clinical setting.

BACKGROUND: Carcinogenic products in the exhaled breath of cancer patients are of growing medical interest as they can serve as noninvasive disease markers. Breath analysis can be used as an alternative or complementary diagnostic tool in breast cancer patients who have a different pattern of chemical composition in their breath. This study aims to verify the existence of specific volatile organic compounds (VOCs) in the breath of breast cancer patients. METHODS: This prospective study included ten patients suffering from breast cancer and ten healthy pair-matched women. Breath samples of each member of the two respective groups were taken and scanned by gas chromatography/mass spectometry for the presence of volatile organic compounds such as alkanes, ketones, halogenated hydrocarbon, aldehydes, and esters. RESULTS: The spectrum of VOCs differed significantly within the two groups. Five specific VOCs could be identified as typical discriminatory markers in the breath samples. Four VOCs were elevated in the healthy controls, one specific VOC was found to be elevated in women affected by breast cancer CONCLUSIONS: This pilot study revealed a specific VOC pattern using gas chromatography in the breath of breast cancer patients. Five specific breast cancer-VOCs were identified. At relatively low cost the identification of VOCs may be used to detect breast cancer.

Modelling Chlamydia and HPV co-infection in patient-derived ectocervix organoids reveals distinct cellular reprogramming.

Coinfections with pathogenic microbes continually confront cervical mucosa, yet their implications in pathogenesis remain unclear. Lack of in-vitro models recapitulating cervical epithelium has been a bottleneck to study coinfections. Using patient-derived ectocervical organoids, we systematically modeled individual and coinfection dynamics of Human papillomavirus (HPV)16 E6E7 and Chlamydia, associated with carcinogenesis. The ectocervical stem cells were genetically manipulated to introduce E6E7 oncogenes to mimic HPV16 integration. Organoids from these stem cells develop the characteristics of precancerous lesions while retaining the self-renewal capacity and organize into mature stratified epithelium similar to healthy organoids. HPV16 E6E7 interferes with Chlamydia development and induces persistence. Unique transcriptional and post-translational responses induced by Chlamydia and HPV lead to distinct reprogramming of host cell processes. Strikingly, Chlamydia impedes HPV-induced mechanisms that maintain cellular and genome integrity, including mismatch repair in the stem cells. Together, our study employing organoids demonstrates the hazard of multiple infections and the unique cellular microenvironment they create, potentially contributing to neoplastic progression.

Prevalence of lymph nodes in the parametrium of radical vaginal trachelectomy (RVT) specimen.

OBJECTIVE: In order to evaluate radicality in fertility preserving surgery in women with early invasive cervical cancer we analyzed the parametrium of specimens of patients treated by radical vaginal trachelectomy for the presence of lymph nodes. We tried to identify morphologic factors associated with the presence of parametrial lymph nodes. METHODS: We analyzed surgical specimens of 112 patients who underwent radical trachelectomy between June 2004 and April 2009 at the Department of Gynecologic Oncology at Charité Campus Benjamin Franklin and Campus Mitte. All parametrial tissue was step sectioned and a total of 1878H&E stained histological sections were analyzed. RESULTS: In 8 patients (7.1%) a total of 13 lymph nodes were detected. Five lymph nodes in four patients had been primarily detected by routine histological examination. In one of these patients (0.9%) a 2mm lymph node metastasis was found. Serial sectioning revealed additional seven lymph nodes in four patients. The thickness of parametrium correlated significantly with the presence of lymph nodes in the parametrium. CONCLUSION: The presence of small lymph nodes in the parametrium of specimens of radical trachelectomy is low. In patients with early-stage cervical cancer, the incidence of metastasis is less than 1%. Preoperative assessment of the volume of the parametrium may indicate which patients need parametrial resection.