Successful Preventive Treatment of Oncogenic Transforming HPV Infections in Low-Grade Cytology (ASC-US/LSIL) Patients with an Adsorptive and Antioxidant Vaginal Gel.

OBJECTIVE: This study aimed to investigate the preventive effect of a vaginal gel on p16/Ki-67-positive abnormal cytological cervical findings (ASC-US, LSIL) and hr-HPV in women. METHODS: The study included 134 women with p16/Ki-67-positive ASC-US or LSIL. Participants were selected from a randomized controlled trial that focused on women with histological diagnoses of p16-positive CIN1 lesions or CIN2. In the treatment group (TG), 57 patients applied the vaginal gel daily for three months, while 77 patients in the "watchful wait" control group (CG) received no treatment. The study's endpoints were cytological development, p16/Ki-67 and hr-HPV clearances. RESULTS: At three months, cytopathological results improved in 74% (42/57) of patients in the TG, compared with 18% (14/77) in the CG. Progression occurred in 7% (4/57) of TG patients compared with 18% (14/77) of CG patients. The p16/Ki-67 status changed statistically significantly in favor of the TG (p < 0.001), with 83% (47/57) becoming negative, compared with 18% (14/77) in the CG. The prevalence of hr-HPV decreased significantly in the TG by 51%, and by 9% in the CG (p < 0.001). CONCLUSIONS: Topical application of the gel resulted in statistically significant clearance of hr-HPV and p16/Ki-67 concomitant with amelioration of cytological findings, thus providing effective prevention and protection against oncogenic development. TRIAL REGISTRATION: ISRCTN11009040, on 10 December 2019.

A new titanium-covered transobturator tape for surgical treatment of stress urinary incontinence.

INTRODUCTION AND HYPOTHESIS: To assess the long-term satisfaction, cure rate and safety of a new titanium-covered transobturator tape compared to polypropylene tape for the treatment of stress urinary incontinence (SUI). METHODS: A prospective study was conducted with 151 patients. Seventy patients underwent transobturator sling surgery with titanium tape from 2011 to 2019, and a historical control group (CG) of 81 patients was treated with a noncoated tape and underwent incontinence surgery from 1999 to 2009. We compared patient-reported outcome measures (PROMs) with the incontinence outcome questionnaire (IOQ). RESULTS: The median follow-up was 2½ years in both groups. Based on responses to the IOQ, a statistically significantly shorter time of recovery (IOQ 15: 21.3 ± 26.4 [TG], 40.2 ± 38.5 [CG], p = 0.02), improvement of sex life (IOQ 13: 34.1 ± 29.4 [TG] vs. 65.3 ± 35.6 [CG], p = 0.01) and less voiding dysfunction (IOQ 19: 30.9 ± 28.1 [CG], 9.3 ± 18.6 [TG], p = 0.01) were observed in the TG. Objectively, no postoperative urinary retention was observed in the TG, but four cases were described in the CG. Ten patients needed a reoperation for SUI in the CG compared to three in the TG (p = 0.03). CONCLUSION: The titanium-covered transobturator sling had superior recovery time, improved sexual function and reduced reoperation rate compared to a historical polypropylene group.

Removal of a Giant Cyst of the Left Ovary from a Pregnant Woman in the First Trimester by Laparoscopic Surgery under Spinal Anesthesia during the COVID-19 Pandemic.

This paper reports a case of a 21 year old primigravida at 6 weeks gestation, suffering from important abdominal pain, who was admitted into the medical center with a giant cyst of 28 × 20 cm on her left ovary. A torsion of the ovarian cyst was suspected. Her COVID-19 status was unknown. In view of the emergency of the situation and the COVID-19 pandemic, laparoscopy in spinal anesthesia was performed. The patient remained conscious during the surgical intervention and tolerated it well apart from a slight dyspnea, which was easily eliminated by changing her body position and decreasing the pneumoperitoneum pressure. The ovarian cyst was removed by enlarging the trocar incision. The patient recovered with neither incident nor pregnancy loss. COVID-19-related complications can induce adverse pregnancy outcomes. Under general anesthesia, patients with COVID-19 are at risk of severe pneumonia and of passing their infection to the medical personnel. To avoid such complications in non-specialized centers, laparoscopy should be performed in regional anesthesia. Laparoscopy in spinal anesthesia can be performed safely on pregnant patients by placing them in the proper position, using a low pneumoperitoneum, and monitoring the hemodynamics. During early pregnancy, general anesthesia induces a higher risk of teratogenic effects and of miscarriage.

Laparoscopy in Gynecologic and Abdominal Surgery in Regional (Spinal, Peridural) Anesthesia, the Utility of the Technique during COVID-19 Pandemic.

BACKGROUND: laparoscopic surgery is mainly performed in general anesthesia. Symptomatic patients infected with COVID-19 needing surgery are however at higher risk for COVID-19 complications in general anesthesia than in regional anesthesia. Even so, Covid transfection is a hazard to medical personnel during the intubation procedure and treatment drugs may be in shortage during a pandemic. Recovery and hospital stay are also shorter after laparoscopy. Laparoscopy performed in regional anesthesia may have several advantages in limiting Covid. METHODS: international literature on the risk of COVID-19 complications development was searched. 3 topics concerning laparoscopic surgery were reviewed: (1) Achievements in laparoscopy; (2) Advantages of regional anesthesia compared to general anesthesia; (3) Feasibility to perform laparoscopy in regional anesthesia in COVID-19 pandemic. The authors reviewed abstracts and full-text articles concerning laparoscopic surgery, gynecology, anesthesia and COVID-19. Studies published in PubMed, Embase, Cochrane Library and found in Google Scholar before 1st FEB, 2021 were retrieved and analyzed. RESULTS: a total of 83 studies were found, all of them written in English. 17 studies could be found in gynecology and in general surgery about laparoscopy with regional anesthesia. In Covid time only one study compared laparoscopic surgery in general anesthesia to laparotomy and another study laparotomy in general anesthesia to regional anesthesia. Laparoscopy showed no disadvantage compared to laparotomy in Covid pandemic and in another study laparotomy in general anesthesia was associated with higher mortality and more pulmonary complications. Trendelenburg position can be a threat if used by inexperienced personnel and can induce unintended anesthesia of breathing organs. On the other hand Trendelenburg position has advantages for cardiovascular and pulmonary functions. Pneumoperitoneum of low CO2 pressure is well tolerated by patients. CONCLUSIONS: elective surgery should be postponed in symptomatic Covid patients. In inevitable emergency surgery intubation anesthesia in COVID-19 pandemic is as far as possible to be avoided. In COVID-19 pandemic, regional anesthesia is the preferred choice. The optimum may be the combination of laparoscopic surgery with regional anesthesia. Reducing the pneumoperitoneum is a good compromise for the comfort of patients and surgeons. A special case is gynecology, which needs to be performed in Trendelenburg position to free pelvic organs.

An Adsorptive and Antioxidant Vaginal Gel Clears High-Risk HPV- and p16/Ki-67-Associated Abnormal Cytological Cervical Findings: A post-hoc Subgroup Analysis of a Prospective Randomized Controlled Trial on CIN2 and p16 Positive CIN1.

Objective: To analyze the course of p16/Ki-67-positive abnormal cytological cervical findings and high risk (hr)-HPV- and p16/Ki-67-clearances in women treated with a vaginal gel. Methods: 172 women with a histological diagnosis of CIN2 or p16-positive CIN1 lesions were selected based on a positive cytological p16/Ki-67 test. For 3 months, 75 patients in the active arm (AA) daily administered 5 ml of a vaginal gel. Ninety seven patients in the control arm (CA) underwent no treatment ("watchful waiting"). Endpoints were cytological evolution, p16/Ki-67- and hr-HPV-clearances. Results: At 3 months, cytological regression was observed in 76% (57/75) of patients in the AA compared with 25% (24/97) in the CA. Progression occurred in 5% (4/75) of the AA compared with 15% (15/97) of the CA. The p16/Ki-67 status change was statistically significantly (p < 0.001) in favor of the AA: 77% (58/75) became negative compared to 21% (20/97) in the CA. hr-HPV prevalence decreased significantly (p < 0.001) in the AA from 87 to 44%, while increasing in the CA from 78 to 84%. Cytological regression and p16/Ki-67 changes persisted in the AA at 6 months. Conclusions: The vaginal gel significantly cleared hr-HPV and p16/Ki-67 and was associated with improved cytological findings, thereby potentially offering an effective option against oncogenic risk. Clinical Trial Registration: Identifier: [ISRCTN11009040].

Metformin, the Rise of a New Medical Therapy for Endometriosis? A Systematic Review of the Literature.

Medical treatments for endometriosis aim to control pain symptoms and stop progression of endometriotic lesions. However, their adverse effects and their contraceptive effect in women who desire pregnancy, limit their long terms use. Although there is only one study investigating the effects of metformin on women with endometriosis, metformin seems to have a unique therapeutic potential. It may be a helpful anti-inflammatory and antiproliferative agent in the treatment of endometriosis. As such metformin may be more beneficial thanks to the lack of serious side effects.

Efficacy and safety of an adsorbent and anti-oxidative vaginal gel on CIN1 and 2, on high-risk HPV, and on p16/Ki-67: a randomized controlled trial.

PURPOSE: The effect of SAM vaginal gel, a medical device containing adsorptive silicon dioxide and antioxidative sodium selenite and citric acid, on histologically-proven cervical intraepithelial neoplasia type 2 (CIN2) as well as p16 positive CIN1, and on the presence of the onco-marker p16 was investigated. METHODS: 216 women aged 25-60 years were randomized to either receive an intravaginal daily dose of SAM gel for three 28-day periods, or be followed-up without intervention. The primary endpoint was efficacy, defined as a combined histological and cytological regression. At baseline and after 3 months participants had: a guided biopsy including p16 immunohistochemical (IHC) staining, only if a lesion was visible at colposcopy; a cervical smear for cytology, high-risk human papillomavirus (hr-HPV) and a p16/Ki-67 test. At 6 months a further cytology and p16/Ki-67 test was performed. RESULTS: Regression of CIN lesions was observed in 78 out of 108 patients (72.2%) in the SAM gel arm and in 27 out of 108 patients (25.0%) in the control arm. Similarly, the change in the p16/Ki-67 cytological test status was significantly in favor of the treatment arm. The prevalence of hr-HPV decreased significantly (p < 0.001) in the treatment arm, from 87.0% to 39.8%, while it slightly increased in the control arm, from 78.7% to 83.3%. At 6 months the cytological regression in the treatment group and the highly significant effect on p16/Ki-67 was still present. CONCLUSION: SAM vaginal gel enhances the regression of cervical lesions and clears hr-HPV and p16/Ki-67 in smears significantly, thus offering an active non-destructive management to prevent cervical cancer. TRIAL REGISTRATION NUMBER: ISRCTN11009040, date of registration: 10/12/2019; https://doi.org/10.1186/ISRCTN11009040 ; retrospectively registered.

It Is Necessary to Purpose an Add-on to the American Classification of Endometriosis? This Disease Can Be Compared to a Malignant Proliferation While Remaining Benign in Most Cases. EndoGram® Is a New Profile Witness of Its Evolutionary Potential.

Endometriosis is a curious pathology that has been the topic of many international publications. Its etiology remains mysterious but seems to have multiple causes. It is a complex disease whose lesions are very heterogeneous in where they can occur (deep endometriosis, superficial, ovarian cyst), extent, associated symptoms, evolution or aggressiveness of the disease, and response to treatments. Furthermore, it evolves in pushes, remains autonomous, and is responsible for both superficial and deep lesions that explain its two most well know challenges: pain and infertility. It has always been classified by the size of its anatomical lesions-Acosta classification (1), revised by the American fertility society (AFS) (2), and the American society of reproductive medicine (ASRM) classification with a description of the disease at different stages: minimal (score of 1 to 5), mild (3-12), moderate (16 to 40), and severe (>40) (13). If this classification provides a complete repertoire of implants (anatomic) (10), the attribution of points is arbitrary. In fact, the size of the lesions is not synonymous with the difficulty to treat them surgically. Their location, if deep, is larger than the size of ovarian endometriomas. In addition, small anatomical but evaluative lesions will have a larger impact than big fibrous and stable lesions (Figure 1). Thus, attempts to explain their inflammatory side effects have been proposed (14, 15). The French classification nodule, ovaries, adhesions, tube, and inflammation (FOATI) (10) has had the merit of taking this phenomenon into account. In our opinion, we must go much further and propose an amendment in this classification, taking into account the evolution of the lesions and their deep molecular biology because in reality, the lesions are not at the same stage.

Endometriotic Mass After Hysterectomy in a 61 Year Old Post-menopausal Woman: A Case Report and Update.

Endometriosis is a common, hormone-dependent gynecologic disease. Undiagnosed in large proportion of women, managing therapies depend on the impact of quality of life and includes hormonal treatment and pelvic surgery. Less likely endometriosis can occur in post-menopausal women. Malignant transformation of endometriosis is a rare but well-described process, most of time occurring in the ovary, and justifies the practitioner not to underestimate this pathology. We present a case of a 61 year old woman with a symptomatic endometriotic pelvic mass, status post hysterectomy, with no history of endometriosis diagnosed beforehand.

Pseudomyxoma Peritonei: A Case Report Diagnosed in a 47-Year-Old Woman with Chronic Pelvic Abdominal Pain and Appendicular Origin: Review of the Literature and Management.

The authors report a case of pseudomyxoma peritonei with gelatinous peritoneum in a 47-year-old-woman. The main symptom for discovery was a chronic pelvic abdominal pain. This disease is particularly rare. The gelatinous substance is often associated with a malignant ovarian tumor or appendicitis perforated. Currently, on the whole, an exploratory laparoscopy allows diagnosis, biopsies, and appendectomy. The treatment is essentially surgical. The prognosis depends on grade (1/3) and response to chemotherapy. This case was presented to the tumor board.

Dissemination of intraperitoneal ovarian cancer: Discussion of mechanisms and demonstration of lymphatic spreading in ovarian cancer model.

Ovarian cancer is often accompanied by severe ascites. This complication aggravates the disease per se and the chances for its successful treatment. The etiology of ascites is not well understood nor are efficient therapies for ascites available. These empirical observations support the view that ascites might be caused by blocking of lymphatic vessels. Furthermore, it suggests that cancer cells might be the blocking agent and could use lymphatic vessels for metastatic spreading. To test this hypothesis, we used labeled cancer cells in an immuno-competent animal model of ovarian cancer and followed their dissemination. These NuTu-19 cells are ovarian cancer cells derived from normal rat ovarian epithelial cells, the origin of the most frequent ovarian cancer. Thus studying NuTu-19 cell behavior in an animal model is likely to reflect the progression of the human disease. To unambiguously document the migration of NuTu-19 cells from the peritoneum to remote organs, we generated EGFP expressing NuTu-19 cells by transduction with EGFP-lentiviral vectors. The EGFP positive NuTu-19 cells were injected intraperitoneally into immuno-competent FISHER 344 rats, and the metastatic spreading was monitored. Metastases were observed on the peritoneum, the omentum and in the parathymus. This clearly demonstrates that systemic spreading of NuTu-19 ovarian cancer cells is conducted by lymphatic ways. Animals die 7 weeks after injection, with severe ascites, which suggests that blockage of lymphatic drainage by the cancer cell growth is an important complication of the disease.

The recurrence of cervical intraepithelial neoplasia in HIV-positive women: a review of the literature.

The objective of this study was to assess the available evidence on the outcome of cervical intraepithelial neoplasia (CIN) in HIV-positive women after conization. We performed a literature search of Medline and Cochrane libraries to locate published articles reporting about the rate of recurrence of CIN after excisional treatment in patients with negative surgical margins. Out of 15 articles, five studies reported recurrence rate of CIN in margin negative patients. The recurrence rate of CIN after conization in HIV-infected women ranges from 20% to 75%. No conclusions can be drawn about the impact of CD4 cell counts on the recurrence rate. Available evidence suggests that standard excisional treatments for CIN are associated with high rates of recurrence in HIV-positive women. Despite the fact that the evidence is limited because of the few number of eligible studies, this issue should be considered in the management of HIV-positive patient with CIN.

Time-dependent hexaminolaevulinate induced protoporphyrin IX distribution after topical application in patients with cervical intraepithelial neoplasia: A fluorescence microscopy study.

BACKGROUND AND OBJECTIVES: Compared to the conventional management of cervical intraepithelial neoplasia (CIN) the potential advantage of photodynamic therapy (PDT) for the treatment of cervical human papilloma virus (HPV)-related disease encompasses a minimal invasive procedure with reduced risk of profuse bleeding as a consequence of conization, and possibly more favorable long-term results avoiding cervical stenosis. At present little is known about the precise time-dependent distribution and histological localization of hexaminolaevulinate (HAL) induced protoporphyrin IX (PPIX) fluorescence in healthy tissue and in CIN. The aim of this study was to use ex vivo fluorescence microscopy to determine whether PPIX is selectively induced by neoplastic cells of the cervical epithelium at various times after topical application. STUDY DESIGN/MATERIALS AND METHODS: Cold cream containing 0.5% HAL was applied by means of cervical cap over various periods of time. We analyzed 52 healthy cervical mucosa and 84 CINs. RESULTS: At time delay 100 (+/-10) minutes, high epithelial fluorescence and a significant selectivity between epithelium and underlying lamina propria was found. By contrast, no significant difference between healthy and neoplastic tissues, or between low and high-grade epithelial dysplasia (P > or = 0.05), was observed at any time point. CONCLUSIONS: Application of HAL 0.5% cream to the cervix induced selective fluorescence in epithelial cells. The optimal ratio with a homogeneous PPIX distribution was obtained after 100 ( +/- 10) minutes cream application, which should be evaluated further for PDT.

Intraperitoneal photodynamic therapy in the Fischer 344 rat using 5-aminolevulinic acid and violet laser light: a toxicity study.

OBJECTIVE: Our study was designed to investigate 5-aminolevulinic acid (ALA) as a candidate for intraperitoneal photodynamic therapy (IP-PDT). The toxicity of IP-PDT and the effects of IP-PDT on abdominal and pelvic organs, particularly the small intestine, were investigated after ALA administration and illumination with violet laser light. STUDY DESIGN AND RESULTS: The toxicity of IP-PDT was evaluated in Fischer 344 rats in two ways. In the first part of the study local PDT effects on the intestine were analyzed histologically. Violet laser light (lambda: 406-415 nm) was applied as a 2 cm diameter spot on the intestine 3 h after intraperitoneal (i.p.) administration of 50 mg/kg ALA. (A) Histological tissue samples were taken 0 min, 6 h and 1, 2 and 3 days after treatment (optical dose 3.2 J/cm(2)). Immediately after local PDT (3.2 J/cm(2), 50 mg/kg ALA) showed no effect on the intestine. However, 6 h post PDT there was complete destruction of the mesothelial lining and the outer (longitudinal) smooth muscle. Ganglion cells of the myenteric (Auerbach) plexus were also destroyed. The inner circular smooth muscle, the muscularis mucosa and the lamina propria were unharmed. Marked lymphectasia was present at this time. (B) To determine the threshold light dose of tissue destruction caused by PDT, different optical doses (1.6, 3.2, 6.4 J/cm(2)) were administered and histologic analysis of tissue samples were obtained 1 day post treatment. Destruction of the entire external musculature, submucosal structures and muscularis mucosa of the intestine at the illumination site could be observed above 1.6 J/cm(2) (50 mg/kg ALA). In the second part of the study whole peritoneal cavity PDT (WPC-PDT) was performed by illumination of the whole peritoneal cavity with 1.6 J/cm(2) violet light 3 h after ALA administration using different drug doses (200, 100 and 50 mg/kg). WPC-PDT showed lethal toxicity with a drug dose above 50 mg/kg ALA at 1.6 J/cm(2). The probable cause of death in the first 3 days after IP-PDT was rhabdomyolysis, whereas when death occurred at longer time intervals, megaintestine associated with significant damage could be observed; however, without perforation of the intestinal wall. CONCLUSION: In rats WPC-PDT with 50 mg/kg ALA, 1.6 J/cm2 at lambda=415 nm was the maximum tolerable light dose. This dose is likely to be above the threshold of destruction of ovarian cancer micrometastasis.