(1) Background: Cervical intraepithelial neoplasia (CIN) of long-term persistence or associated with individual treatment indications often requires highly invasive treatments. These are associated with risks of bleeding, infertility, and pregnancy complications. For low- and middle-income countries (LMICs), standard treatment procedures are difficult to implement and manage. We characterized the application of the highly energized gas “noninvasive physical plasma” (NIPP) for tissue devitalization and the treatment of CIN. (2) Methods: We report the establishment of a promising tissue devitalization procedure by NIPP application. The procedure was characterized at the in vitro, ex vivo and in vivo levels. We performed the first prospective, single-armed phase-IIb trial in 20 CIN1/2 patients (NCT03218436). (3) Results: NIPP-treated cervical cancer cells used as dysplastic in vitro model exhibited significant cell growth retardation due to DNA damage, cell cycle arrest and apoptosis. Ex vivo and in vivo tissue assessments showed a highly noninvasive and tissue-preserving treatment procedure which induces transmucosal tissue devitalization. Twenty participants were treated with NIPP and attended a 24-week follow-up. Treatment success was achieved in 19 (95%) participants without postinterventional complications other than mild to moderate discomfort during application. (4) Conclusions: The results from this study preliminarily suggest that NIPP could be used for an effective and tissue-preserving treatment for CIN without the disadvantages of standard treatments. However, randomized controlled trials must confirm the efficacy and noninferiority of NIPP compared to standard treatments.

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.

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.

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.

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.