Human tissue-resident peritoneal macrophages reveal resistance towards oxidative cell stress induced by non-invasive physical plasma.

In the context of multimodal treatments for abdominal cancer, including procedures such as cytoreductive surgery and intraperitoneal chemotherapy, recurrence rates remain high, and long-term survival benefits are uncertain due to post-operative complications. Notably, treatment-limiting side effects often arise from an uncontrolled activation of the immune system, particularly peritoneally localized macrophages, leading to massive cytokine secretion and phenotype changes. Exploring alternatives, an increasing number of studies investigated the potential of plasma-activated liquids (PAL) for adjuvant peritoneal cancer treatment, aiming to mitigate side effects, preserve healthy tissue, and reduce cytotoxicity towards non-cancer cells. To assess the non-toxicity of PAL, we isolated primary human macrophages from the peritoneum and subjected them to PAL exposure. Employing an extensive methodological spectrum, including flow cytometry, Raman microspectroscopy, and DigiWest protein analysis, we observed a pronounced resistance of macrophages towards PAL. This resistance was characterized by an upregulation of proliferation and anti-oxidative pathways, countering PAL-derived oxidative stress-induced cell death. The observed cellular effects of PAL treatment on human tissue-resident peritoneal macrophages unveil a potential avenue for PAL-derived immunomodulatory effects within the human peritoneal cavity. Our findings contribute to understanding the intricate interplay between PAL and macrophages, shedding light on the promising prospects for PAL in the adjuvant treatment of peritoneal cancer.

Hyperspectral imaging as a new diagnostic tool for cervical intraepithelial neoplasia.

PURPOSE: Cervical cancer screening by visual inspection with acetic acid (VIA) during colposcopy can be challenging and is highly dependent on the clinical experience of the examiner. Health-care systems lack qualified physicians able to perform the examination in both industrialized and low- and middle-income countries. Previous work has shown the general potential of hyperspectral imaging (HSI) to discriminate CIN from normal tissue, but clinical translation has been limited due to the lack of medically approved HSI systems. METHODS: In this study, we evaluate the feasibility of a commercially available HSI system for CIN detection in a prospective monocentric clinical trial. RESULTS: By obtaining spectral fingerprints of 41 patients with CIN 1-3 we show that HSI-based differentiation between CIN and normal tissue is possible with high statistical significance. Major spectral differences were seen in the 555-585 wavelength area. CONCLUSION: HSI advances tissue differentiation by associating each pixel with high-dimensional spectra and thereby obtains morphological and biochemical information of the observed tissue. Currently available and medically approved HSI systems may represent a contact- and marker-free examiner-independent method for the diagnosis of CIN.

Improvement in Fertility and Pain after Endometriosis Resection and Adhesion Prevention with 4DryField® PH: Follow-up of a Randomized Controlled Clinical Trial.

BACKGROUND: Adhesions after endometriosis resection are frequent and the most common causes for chronic pain and secondary infertility. Primary results of our randomized controlled trial (RCT) on adhesion prevention after deep infiltrating endometriosis (DIE) resection using the gel barrier 4DryField® PH showed 85% adhesion reduction in second-look surgeries. Secondary endpoint data on fertility and pain development were collected during 12-month follow-ups. METHODS: This RCT comprised 50 patients. Preoperatively and after 1, 6 and 12 months, pain scores for cycle-independent pelvic pain, dysmenorrhea, dyspareunia, dyschezia, and dysuria, as well as the number of pregnancies, were recorded,. RESULTS: The pregnancy rate in the intervention group was significantly higher (p < 0.05). Pain development was also improved: after 12 months, all 5 subscores were lower in the intervention group and improvements were more pronounced, most prominently concerning cycle-independent pelvic pain and dysmenorrhea, the two subcategories with the highest preoperative scores and, therefore, the highest relevance for the patients. Cycle-independent pelvic pain even recurred in the control group, while barrier application prevented this. CONCLUSIONS: Considering the known causal link between adhesions and pain, it is apparent that the favourable outcomes in the intervention group are linked to effective adhesion prevention. The significant increase in pregnancies is remarkable.

Improved preoperative risk stratification in endometrial carcinoma patients: external validation of the ENDORISK Bayesian network model in a large population-based case series.

PURPOSE: Preoperative risk stratification of newly diagnosed endometrial carcinoma (EC) patients has been hindered by only moderate prediction performance for many years. Recently ENDORISK, a Bayesian network model, showed high predictive performance. It was the aim of this study to validate ENDORISK by applying the model to a population-based case series of EC patients. METHODS: ENDORISK was applied to a retrospective cohort of women surgically treated for EC from 2003 to 2013. Prediction accuracy for LNM as well as 5-year DSS was investigated. The model's overall performance was quantified by the Brier score, discriminative performance by area under the curve (AUC). RESULTS: A complete dataset was evaluable from 247 patients. 78.1% cases were endometrioid histotype. The majority of patients (n = 156;63.2%) had stage IA disease. Overall, positive lymph nodes were found in 20 (8.1%) patients. Using ENDORISK predicted probabilities, most (n = 156;63.2%) patients have been assigned to low or very low risk group with a false-negative rate of 0.6%. AUC for LNM prediction was 0.851 [95% confidence interval (CI) 0.761-0.941] with a Brier score of 0.06. For 5-year DSS the AUC was 0.698 (95% CI 0.595-0.800) as Brier score has been calculated 0.09. CONCLUSIONS: We were able to successfully validate ENDORISK for prediction of LNM and 5-year DSS. Next steps will now have to focus on ENDORISK performance in daily clinical practice. In addition, incorporating TCGA-derived molecular subtypes will be of key importance for future extended use. This study may support further promoting of data-based decision-making tools for personalized treatment of EC.

Hybrid argon plasma coagulation (HybridAPC) versus sharp excision for the treatment of endometriosis: a prospective randomized clinical trial.

PURPOSE: Endometriosis is a benign, but potentially serious gynaecological condition in terms of abdominal pain and impaired fertility. Laparoscopic excision techniques are considered the therapeutic standard. HybridAPC is presented as a novel technique for the non-contact thermal ablation of peritoneal endometriosis with simultaneous protection of the underlying thermosensitive structures by creating a needle-free elevated fluid cushion which enables a safer exposure and distance, as well as potentially improved peritoneal conditioning prior to APC. METHODS: In this prospective randomized clinical trial, 39 patients with 132 superficial endometriotic lesions in total were treated with HybridAPC or sharp excision in an initial laparoscopic procedure according to randomization. In a second-look laparoscopy, adhesion formation was rated macroscopically. Histologic samples were taken from previously treated areas for evaluation of eradication rate. RESULTS: The eradication rate was not significantly different between HybridAPC treatment and sharp excision (65 vs. 81%, p = .55). Adhesions formed in 5% of HybridAPC-treated lesions and in 10% after sharp excision (p = .49). HybridAPC treatment was significantly faster than sharp excision (69 vs. 106 s, p < .05). No intra- and postoperative complications were registered. CONCLUSION: This clinical trial demonstrates the feasibility of this novel surgical technique with a promising impact on adhesion prevention. Compared to sharp excision, HybridAPC is likely to be a safe, tissue-preserving, and fast method for the treatment of peritoneal endometriosis.

Cell Type-Specific Anti-Adhesion Properties of Peritoneal Cell Treatment with Plasma-Activated Media (PAM).

Postoperative abdominal adhesions are responsible for serious clinical disorders. Administration of plasma-activated media (PAM) to cell type-specific modulated proliferation and protein biosynthesis is a promising therapeutic strategy to prevent pathological cell responses in the context of wound healing disorders. We analyzed PAM as a therapeutic option based on cell type-specific anti-adhesive responses. Primary human peritoneal fibroblasts and mesothelial cells were isolated, characterized and exposed to different PAM dosages. Cell type-specific PAM effects on different cell components were identified by contact- and marker-independent Raman imaging, followed by thorough validation by specific molecular biological methods. The investigation revealed cell type-specific molecular responses after PAM treatment, including significant cell growth retardation in peritoneal fibroblasts due to transient DNA damage, cell cycle arrest and apoptosis. We identified a therapeutic dose window wherein specifically pro-adhesive peritoneal fibroblasts were targeted, whereas peritoneal mesothelial cells retained their anti-adhesive potential of epithelial wound closure. Finally, we demonstrate that PAM treatment of peritoneal fibroblasts reduced the expression and secretion of pro-adhesive cytokines and extracellular matrix proteins. Altogether, we provide insights into biochemical PAM mechanisms which lead to cell type-specific pro-therapeutic cell responses. This may open the door for the prevention of pro-adhesive clinical disorders.

Absorbable versus non-absorbable sutures for vaginal mesh attachment during sacrocolpopexy: a randomized controlled trial.

INTRODUCTION AND HYPOTHESIS: The purpose of the study was to analyze anatomical and functional outcomes after sacrocolpopexy (SCP) for vaginal vault prolapse pelvic organ prolapse quantification (POPQ) II-III by random use of absorbable (Vicryl) and non-absorbable sutures (Ethibond) for vaginal mesh fixation. METHODS: This study was designed as a two-center randomized controlled study (RCT). The primary objective was to evaluate the anatomical outcome. Success was defined when the vaginal apex (point C; POPQ) did not descend more than 50% of the total vaginal length (tvl) during Valsalva. Patients completed a pelvic examination incorporating the POPQ and questionnaires (the German pelvic floor questionnaire and the PISQ-12 questionnaire) at baseline and 6 months postsurgery. Perioperative adverse events (AE) were recorded. Sample size calculations, based on a 10% non-inferiority limit required 100 participants per group, with power = 90%. RESULTS: In 190 out of 195 women (ETH group n = 96; VIC group n = 94) anatomical success was achieved. The relative risk of anatomical success failure in the VIC group versus the ETH group was 0.69, with a 95% confidence interval 0.12-4.02. The change in the symptom scores did not differ significantly between the ETH and the VIC group. In the ETH group, three suture penetrations into the vagina were observed, and none in the VIC group 6 months postoperatively. CONCLUSIONS: Anatomical success after SCP for vaginal vault prolapse POPQ II-III is not affected by suture type for vaginal monofilament mesh attachment. Moreover, we did not see any differences in functional outcomes between the two groups. Three suture penetrations into the vagina were observed in the ETH group, and none in the VIC group 6 months postoperatively.

Adhesion prevention after endometriosis surgery - results of a randomized, controlled clinical trial with second-look laparoscopy.

PURPOSE: Adhesion formation after endometriosis surgery is a severe problem affecting up to 90% of patients. Possible complications include chronic pain, ileus, and secondary infertility. Therefore, effective adhesion prophylaxis is desirable, for which the adhesion barrier 4DryField® PH is evaluated in the present clinical study. It is a starch-based powder that forms a gel after irrigation with saline solution and thus separates surgical sites as physical barrier for adhesion prevention. METHODS: Fifty patients with extensive and deep infiltrating endometriosis were included in this prospective, randomized, controlled clinical trial with two-staged laparoscopic approach. The patients were randomized into two groups, one receiving 4DryField® PH and the other irrigation with saline solution for adhesion prevention. Adhesion formation was directly scored during second-look interventions considering incidence, extent, and severity. Adhesion prevention treatment in the second surgery was performed corresponding to the first intervention to evaluate the long-term outcome in the later course. RESULTS: Both groups were comparable with respect to relevant patient parameters. Severity and extent of adhesions were significantly reduced by 85% in the 4DryField® PH group compared to the control group (mean total adhesion score 2.2 vs. 14.2; p = 0.004). Incidence of adhesion formation based on the number of affected sites was significantly reduced by 53% in the intervention vs. control group (mean 1.1 vs. 2.3 sites; p = 0.004). Follow-up of secondary endpoints is not yet completed; results will become available at a later stage. CONCLUSION: Adhesion formation could be reduced significantly by 85% by application of the adhesion barrier 4DryField® PH. TRIAL REGISTRATION: Trial registration main ID: DRKS00014720, secondary ID: U1111-1213-4142; date of registration 09th May 2018.

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

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

Evaluation and management of obstetric genital fistulas treated at a pelvic floor centre in Germany.

BACKGROUND: Obstetric genital fistulas are an uncommon condition in developed countries. We evaluated their causes and management in women treated at a German pelvic floor centre. METHODS: Women who had undergone surgery for obstetric genital fistulas between January 2006 and June 2020 were identified, and their records were reviewed retrospectively. RESULTS: Eleven out of 40 women presented with genitourinary fistulas, and 29 suffered from rectovaginal fistulas. In our cohort, genitourinary fistulas were more common in multiparous women (9/11), and rectovaginal fistulas were more common in primiparous women (24/29). The majority of the genitourinary fistulas were at a high anterior position in the vagina, and all rectovaginal fistulas were at a low posterior position. While all genitourinary fistulas were successfully closed, rectovaginal fistula closure was achieved in 88.65% of cases. Women who suffered from rectovaginal fistulas and were at high risk of recurrence or postoperative functional discomfort and desired another child, we recommended fistula repair in the context of a subsequent delivery. For the first time, pregnancy-related changes in the vaginal wall were used to optimize the success rate of fistula closure. CONCLUSIONS: In developed countries, birth itself can lead to injury-related genital fistulas. As fistula repair lacks evidence-based guidance, management must be tailored to the underlying pathology and the surgeon's experience. Attention should be directed towards preventive obstetric practice and adequate perinatal and postpartum care. Although vesicovaginal fistulas occur rarely, in case of urinary incontinence after delivery, attention should be paid to the patient, and a vesicovaginal fistula should be ruled out. Trial registration Retrospectively registered, DRKS 00022543, 28.07.2020.

Peritoneal Adhesions and their Prevention - Current Trends.

The development of adhesions after gynecologic surgery is a severe problem with ramifications that go beyond the medical complications patients suffer (which most often include pain, obstruction and infertility), since they also impose a huge financial burden on the health care system and increase the workload of surgeons and all personnel involved in surgical follow-up care. Surgical techniques to avoid adhesion formation have not proven to be sufficient and pharmaceutical approaches for their prevention are even less effective, which means that the use of adhesion prevention devices is essential for achieving decent prophylaxis. This review explores the wide range of adhesion prevention products currently available on the market. Particular emphasis is put on prospective randomized controlled clinical trials that include second-look interventions, as these offer the most solid evidence of efficacy. We focused on adhesion scores, which are the most common way to quantify adhesion formation. This enables a direct comparison of the efficacies of different devices. While the greatest amount of data are available for oxidized regenerated cellulose, the outcomes with this adhesion barrier are mediocre and several studies have shown little efficacy. The best results have been achieved using adhesion barriers based on either modified starch, i.e., 4DryField® PH (PlantTec Medical GmbH, Lüneburg, Germany), or expanded polytetrafluoroethylene, i.e., GoreTex (W.L. Gore & Associates, Inc., Medical Products Division, Flagstaff, AZ), albeit the latter, as a non-resorbable barrier, has a huge disadvantage of having to be surgically removed again. Therefore, 4DryField® PH currently appears to be a promising approach and further studies are recommended.

Uterine Fibroids - Current Trends and Strategies.

Fibroids are the most common benign tumors in women of childbearing age and can be found in almost 80-90% of all women by age 50 years. They can cause pain, excessive menstrual bleeding or infertility. The development of fibroids increases with age. Since the age of women in industrial countries who are trying to conceive is generally increasing, there has been a growing demand for minimally invasive and uterine-sparing surgical treatment of fibroids. Whereas the main focus of previous surgical techniques for the treatment of fibroids was enucleation of the tumour with subsequent closure of the uterine incision, modern devices developed over the past decade can destroy fibroids by using ultrasound or radio-frequency without incising the uterine wall. Thus, there is no uterine scar, which would impart a risk of rupture during labour or pregnancy. This article provides an overview of the latest techniques and devices used for uterine-sparing surgical treatment of fibroids. While laparoscopic myomectomy is still the gold standard, novel laparoscopic and transcervical radiofrequency ablation techniques use low-voltage and alternating current to induce heat in the uterine tissue, which triggers necrosis in fibroids. This enables the removal of multiple fibroids without the need for large incisions in the uterine wall. In addition, we address the benefits and potential risks, as well as the impact on fertility and pregnancy, of the different surgical approaches used for the treatment of uterine fibroids.