Vaginal Biopsies Research Articles

Soft Tissue Sarcomas at Atypical Locations in Gynecologic Oncology: A Series of 3 Cases

PurposeThe most frequent primary site of sarcomas in gynecologic oncology is uterus (83%) followed by ovary (8%), vulva and vagina (5%). We present three cases of sarcomas at atypical locations.MethodRecords of cases were retrieved from electronic medical records, and telephonic follow-up was done to know their current status.ResultCase 1: A 26-year-old parous lady presented with complaint of recurrent vulvar mass. Biopsy at our institute revealed myxoid liposarcoma. Metastatic workup was negative. She underwent radical local excision with VY-plasty and bilateral ovarian transposition (BOT) followed by concurrent chemo-radiotherapy. She is disease free at 12 months. Case 2: A 29-year-old lady presented with large bleeding mass arising from right wall of vagina. Histopathology report of vaginal biopsy was high-grade leiomyosarcoma. MRI pelvis with thorax and abdomen scan, examination under anesthesia and cystoscopy revealed non-metastatic operable disease. She underwent radical hysterectomy with vaginectomy with BOT followed by pelvic radiotherapy. At 4-month follow-up, she presented with scalp lesion. Further workup revealed disseminated metastatic disease. She is on palliative chemotherapy at the time of submission or article. Case 3: A 54-year-old lady underwent evaluation for pain abdomen with contrast-enhanced computed tomography which revealed a large omental mass. She had past history of carcinoma cervix 6 years back treated outside with surgery and chemo-radiotherapy. Image-guided biopsy was reported as leiomyosarcoma. Metastatic workup showed no disease elsewhere. She underwent omental mass excision followed by chemotherapy. She is disease free at 13 months.ConclusionSurgery remains the mainstay of treatment in non-metastatic sarcomas. Long-term follow-up of patients is needed in view of their atypical presentation.

Case Report: Radical Vulvectomy V-Y Flap Surgical Procedure in a Woman with Vulva Cancer

Introduction: Vulva cancer is one of the relatively rare malignancies, accounting for only 4% of all malignancies in gynecologic organs. Vulva cancer is often asymptomatic. Surgery is the basic management in patients with earliest-stage vulvar cancer and frequently requires a combined radical vulvectomy followed by inguinal LN dissection through a separate incision. Therefore, the author hopes this case can add insight into the knowledge related to early detection and comprehensive management of vulva cancer. Case Presentation: A woman, 67 years old, referred from Gambiran General Hospital Kediri with a vaginal biopsy result of vulva cancer, came to the Saiful Anwar General Hospital oncology clinic. The patient complained of pain in the pubic area accompanied by tissue growth around the pubic area since August 2023. History of weight loss (+) 10 kg in the past year. History of menopause since 18 years ago. The examination results obtained vital signs: BP 132/79 mmHg, pulse 128x/min, RR 20x/min, temperature 36.5C, height 155 cm, weight 40kg, and BMI 16.64 kg / m2 (underweight). Physical examination of external genitalia revealed a 12x8 cm mass on the right vulva, odour (+). The results of the vulvar biopsy examination on 25/08/2023 were found to be squamous cell carcinoma, well differentiated. The patient is planned for elective-wide excision. The management performed was radical vulvectomy with V-Y flap reconstruction surgery. Conclusion: In this case, it can be concluded vulva cancer is a relatively rare malignancy. The subtype often found is SCC (90-95%). This patient planned for radical vulvectomy using the V-Y flap reconstruction technique with SAB.

Fractional and Microablative CO2 LASER and Radiofrequency in the Treatment of Genitourinary Syndrome of Menopause: A Descriptive Study.

Objectives: This study aimed to evaluate the vagina clinically, cytologically, and histologically before and after treating genitourinary syndrome of menopause (GSM) with fractional microablative carbon dioxide LASER (CO2L), radiofrequency (RF), and estrogen vaginal cream (CT). Methods: Women with moderate-to-severe symptoms of GSM, denoted by a GSM Visual analog scale (VAS) score of >4, were eligible for this study. The patients were randomized into treatment groups. In the energy groups, three vulvovaginal applications were administered monthly. The CT group used 0.5 mg vaginal estriol cream for 14 consecutive days, followed by twice a week for 4 months. The follow-up visits occurred 120 days after the beginning of the treatments. The same parameters obtained at the first visit were re-evaluated: GSM VAS score, Incontinence Quality of Life Questionnaire (I-QOL), gynecological examination determining Vaginal Health Index (VHI), vaginal smear for Vaginal Maturation Value (VMV), and vaginal biopsy. Results: Seventy-one women were included, 48 completed the study and provided adequate samples for analysis (CO2L [21 patients], RF [15 patients], and CT [12 patients]). GSM symptoms, I-QOL, and VHI significantly improved after all proposed treatments, with no significant differences between them. VMV did not change after any treatment; however, only 22.9% of the patients presented with cytological atrophy before treatment. Histological vaginal atrophy was identified in 6 (12.5%) pretreated vaginal samples. After the intervention, all histological parameters were normalized, no tissue damage was observed, and no major clinical complications were observed. Conclusion: CO2L and RF seem to be good alternatives to CT for GSM treatment, with no tissue damage.

Increased Interferon Signaling in Vaginal Tissue of Patients With Primary Sjögren Syndrome.

Vaginal dryness is an important factor influencing sexual function in women with primary Sjögren syndrome (pSS). Previous studies showed a higher degree of inflammation in vaginal biopsies from patients with pSS compared to non-pSS controls. However, the molecular pathways that drive this inflammation remain unclear. Therefore, the aim of this study was to investigate inflammatory pathway activity in the vaginal tissue of patients with pSS. Vaginal biopsies of 8 premenopausal patients with pSS experiencing vaginal dryness and 7 age-matched non-pSS controls were included. Expression of genes involved in inflammation and tissue homeostasis was measured using NanoString technology and validated using TaqMan Real-Time PCR. Vaginal tissue sections were stained by immunohistochemistry for myxovirus resistance protein 1 (MxA) and CD123 (plasmacytoid dendritic cells [pDCs]). The most enriched pathway in vaginal biopsies from patients with pSS compared to non-pSS controls was the interferon (IFN) signaling pathway (P < 0.01). Pathway scores for Janus kinase and signal transducer and activator of transcription (JAK-STAT) and Notch signaling were also higher (P < 0.01 for both pathways). Conversely, transforming growth factor-β signaling and angiogenesis pathway scores were lower in pSS (P = 0.02 and P = 0.04, respectively). Differences in IFN signaling between patients with pSS and non-pSS controls were confirmed by PCR and MxA tissue staining. No CD123+ pDCs were detected in vaginal biopsies. IFN-stimulated gene expression levels correlated positively with CD45+ cell numbers in vaginal biopsies and serum anti-SSA/Ro positivity. Upregulation of IFN signaling in vaginal tissue of women with pSS, along with its association with tissue pathology, suggests that IFNs contribute to inflammation of the vaginal wall and potentially also to clinical symptomatology (ie, vaginal dryness).

Pharmacokinetics of single dose doxycycline in the rectum, vagina, and urethra: implications for prevention of bacterial sexually transmitted infections

Clinical trials showed a single oral dose of doxycycline taken after sex protects against STIs among men who have sex with men (MSM) but not women. Pharmacokinetic data at vaginal, rectal and penile sites of STI exposure are lacking. We examined vaginal, rectal and urethral doxycycline concentrations in men and women to better inform STI prevention. Doxycycline pharmacokinetics in male and female participants 18-59 years of age were evaluated in blood and urine and on rectal and vaginal swabs collected at 1, 2, 4, 8, 24, 48, 72, 96 and 168h after receiving a 200mg oral doxycycline dose in a non-randomised single dose open label single centre study in Atlanta, Georgia. Rectal, vaginal, and cervical biopsies and male urethral swabs were collected 24h after dosing (Trial registration: NCT04860505). Doxycycline was measured by liquid chromatography-mass spectrometry. Eleven male and nine female participants participated in the study. Doxycycline concentrations on rectal and vaginal swabs collected up to 96h after dosing were approximately twice those of plasma and remained above minimum inhibitory concentrations (MICs) for at least four, three, and two days for Chlamydia trachomatis, Treponema pallidum, and tetracycline-sensitive Neisseria gonorrhoeae, respectively. Geometric mean doxycycline concentrations in male urethral secretions (1.166μg/mL; 95% CI 0.568-2.394μg/mL), male rectal (0.596μg/g; 0.442-0.803μg/g), vaginal (0.261μg/g; 0.098-0.696μg/g) and cervical tissue (0.410μg/g; 0.193-0.870μg/g) in biopsies collected 24h after dosing exceeded MICs. Plasma and urine doxycycline levels defined adherence markers up to four and seven days postdosing, respectively. No adverse events were reported in this study. Doxycycline efficiently distributes to the rectum, vagina and urethra. Findings can help explain efficacy of STI prevention by doxycycline. Funded by CDC intramural funds, CDC contract HCVJCG-2020-45044 (to CFK).

Pathological Changes and Pregnancy Outcomes in Cervical Intraepithelial Neoplasia Patients After Cold Knife Conization.

Analyze women treated with underwent cold knife conization (CKC) to remove advanced squamous intraepithelial lesions (CIN) of the cervix. The histopathological upgrading of the lesions previously detected on vaginal biopsy and postoperative pregnancy outcomes of were investigated, to identify high-risk subgroups in women. A retrospective study was conducted at the First Central Hospital of Baoding City from June 2019 to December 2022 to analyze confirmed cases of Cervical Intraepithelial Neoplasia CIN-II and CIN-III. Investigation of pathological changes in postoperative pathological tissues, and to perform binary logistic analysis to identify risk factors for histopathological escalation in postoperative lesions. We analyze the effects of CKC surgery on pregnancy outcomes in patients by comparing against a control group of healthy pregnant women. Out of the 176 patients diagnosed with CIN-II who underwent cervical biopsy, 39 (22.16%) were found to have a final specimen diagnosis of CIN-III, while 7 (3.98%) were downgraded to CIN-I. Among the 108 patients diagnosed with CIN-III who underwent cervical biopsy, 7 cases (6.48%) were ultimately confirmed to have CIN-III. Ki67-positive, p16-positive (OR = 1.13, 95% CI 1.01-1.15), and colposcopy biopsy for CIN-II (OR = 1.59, 95% CI 1.33-3.6) were independent risk factors for pathological upgrade after CKC. Compared with healthy pregnant women, CIN patients had higher rates of premature birth (14.4%), premature rupture of the fetal membrane (13.6%), and cesarean section (37.5%) (P < 0.05). The mode of conception, abortion rate, ectopic pregnancy rate, and postpartum hemorrhage were not different between healthy pregnant women and CIN patients (P > 0.05). Following cervical multi-point biopsy or CKC, along with pathological examination, the accurate diagnosis of cervical lesions is crucial as it allows for more precise identification of such lesions. Additionally, CKC increases the risk of premature birth, premature rupture of membranes, and the need for cesarean section.

The Multidisciplinary Approach to Vaginal Leiomyosarcoma, an Extremely Rare Diagnosis - Case Report

Primary vaginal sarcoma is an extremely rare malignant condition within the field of gynecological pathologies. We present the case of a 53-year old patient with no history of gynecological issues or associated comorbidities who presented to our clinic with recurrent vaginal bleeding during menopause. We want to emphasize the importance of diagnostic management, going through all the necessary steps from local gynecological examination to vaginal biopsy, optimizing results with advanced imaging techniques. Once the histopathological diagnosis of vaginal leiomyosarcoma was established, the therapeutic approach was discussed within a multidisciplinary committee consisting of a gynecologist, surgeon, and oncologist. As a result, the patient underwent tailored surgical intervention relatively quickly after presentation, followed by referral to the oncology department, where she is currently undergoing her third course of adjuvant chemotherapy. Our current objective is the long-term follow-up of the patient and the acquisition of data regarding her survival and quality of life. These facts may contribute in the future to the implementation of standardized therapeutic guidelines for such a rare condition

Abnormal Vaginal Cytology after Total Laparoscopic Hysterectomy in Patients with Cervical Intraepithelial Neoplasia.

To explore the incidence of abnormal vaginal cytology after total laparoscopic hysterectomy for the treatment of cervical intraepithelial neoplasia 3, we retrospectively analyzed the medical records of patients treated at NHO Shikoku Cancer Center (Japan) in 2014-2019. The cases of 99 patients who underwent a laparoscopic (n=36) or open (n=63) hysterectomy and postoperative follow-up were examined. Abnormal vaginal cytology was detected in 13.9% (5/36) of the laparoscopic-surgery (LS) group and 14.3% (9/63) of the open-surgery (OS) group. A vaginal biopsy was performed at the physicians' discretion; one LS patient and six OS patients were diagnosed with vaginal intraepithelial neoplasia. The cumulative incidence of abnormal vaginal cytology at 3 years post-hysterectomy was 21.4% (LS group) and 20.5% (OS group), a nonsignificant difference. A multivariate analysis showed that age > 50 years was the only independent risk factor for abnormal vaginal cytology among the covariates examined including age; body mass index; histories of vaginal delivery, abdominal surgery, and smoking; and surgical approach (hazard ratio 8.11; 95% confidence interval 1.73-37.98; p=0.01). These results suggest that the occurrence of abnormal vaginal cytology after a hysterectomy may not be influenced by the laparoscopic procedure but is associated with older age.

Prevalence and Risk Assessment of Human Papillomavirus Infection in a Bengali Cohort

Cervical cancer is a notable cause of mortality and morbidity among women of reproductive age. Human papillomavirus (HPV) is the leading cause of cervical cancer among women. Among 170 types of HPV; HPV-16 and -18 are responsible for cervical cancer. The overexpression of oncoproteins E6 and E7 are predominantly responsible for causing neoplasia. The presence of koilocytosis/koilocytotic atypia is the diagnostic point of HPV infection in pap smears. To identify the circulating types of HPV and determine the various risk factors associated with HPV infection, 100 vaginal biopsies or swabs were taken from patients suspected with cervical cancer, and qualitative and semi-quantitative real-time PCR were performed. PCR primers (GP5+/GP6+) based on a conserved region of the HPV-L1open reading frame(ORF) gene were used for the detection of HPV strains, while another set of primers was used for detecting the E6 gene (HPV-16) and E7 gene (HPV-18). The results showed an HPV infection rate of 23%. Furthermore, the prevalent genotype was found to be HPV-16 (73.91%), followed by HPV-18 (26.1%), while mixed infections of both HPV-16 and -18 accounted for 21.74%. In addition, an age of above 45 years, multiple pregnancies, low socioeconomic status, postmenopausal state, anemia, and early coitarche were significantly associated with HPV infection. These results provide the basis for the formulation of an appropriate strategy for disease monitoring to determine the frequency and distribution pattern of HPV infection.

Correlation Between Colposcopic Patterns and Histological Grade of Vaginal Intraepithelial Neoplasia: A Retrospective Cohort Study.

Vaginal intraepithelial neoplasia (VaIN) is a rare human papillomavirus (HPV)- related premalignant condition. VaIN lesions are diagnosed histologically through colposcopy-guided biopsies of suspicious areas, conduced by gynecologists with expertise in lower genital tract diseases. The present study aimed to evaluate the accuracy of colposcopy in the diagnosis of VaIN of any grade. We conducted a retrospective analysis on a cohort of 149 women diagnosed with low grade (LG)-VaIN (VaIN1) and high grade (HG)-VaIN (VaIN2-3) between 2010 and 2022 at the "Regional Referral Center for Prevention, Diagnosis and Treatment of HPV-related Genital Disorders", Ospedale Maggiore Policlinico, Milan, Italy. All women had been referred to our center for an abnormal Pap smear or as part of routine follow-up of other HPV-related diseases and had undergone a vaginal biopsy under colposcopic guidance. The distribution of the histological grades of VaIN lesions was the following: 62 women (41.6%) were diagnosed with VaIN1, 51 (34.2%) with VaIN2, and 36 (24.2%) with VaIN3. Grade II (major) abnormal colposcopic patterns were recorded in 71 cases (47.7%) and were more commonly observed in women with VaIN3 (80.6%). However, we found a poor and not statistically significant association between colposcopic and histological grade of VaIN. The sensitivity, specificity, positive predictive value, and negative predictive value of colposcopy for histologically confirmed VaIN were 56.3%, 64.5%, 69% and 51.2%, respectively. The overall diagnostic accuracy of colposcopy was 59.7%. Colposcopy-guided biopsy plays an important role in the diagnosis of VaIN and in the distinction between low and high-grade lesions. Our data show that major colposcopic abnormalities moderately correlate with HG-VaIN and that grade I colposcopic findings do not exclude HG-VaIN, especially VaIN2. Targeted biopsies of suspicious vaginal areas must be performed in all women with an abnormal Pap smear.

Cytology and HPV Co-Testing for Detection of Vaginal Intraepithelial Neoplasia: A Retrospective Study.

(1) Background: Vaginal intraepithelial neoplasia (VaIN) is a rare premalignant disease caused by persistent human papillomavirus (HPV) infection. Diagnosing VaIN is challenging; abnormal cytology and positive HPV tests are usually the first signs, but published data on their accuracy for detecting it are rare and contradictory. The aim of this study is to compare the results of hrHPV and cytology co-testing with the histological findings of the vagina. (2) Methods: In the certified Dysplasia Unit at Erlangen University Hospital, cytology and HPV samples from the uterine cervix or vaginal wall after hysterectomy were obtained between 2015 and 2023 and correlated with histological findings in biopsies from the vaginal wall. Women without vaginal biopsy findings or concomitant cervical disease were excluded. (3) Results: In all, 279 colposcopies in 209 women were included. The histological results were: benign (n = 86), VaIN I/vLSIL (n = 116), VaIN II/vHSIL (n = 41), VaIN III/vHSIL (n = 33), and carcinoma (n = 3). Accuracy for detecting VaIN was higher in women with previous hysterectomies. Positive HPV testing during colposcopy increased the likelihood for VaIN II/III/vHSIL threefold. The detection rate for VaIN III/vHSIL was 50% after hysterectomy and 36.4% without hysterectomy. (4) Conclusions: Women with risk factors for VaIN, including HPV-16 infection or prior HPV-related disease, need careful work-up of the entire vaginal wall. Hysterectomy for HPV-related disease and a history of cervical intraepithelial neoplasia (CIN) also increased the risk for VaIN II/III/vHSIL.

Efficacy of Fractional Laser on Steroid Receptors in GSM Patients.

To compare the efficacy of CO2 fractional laser with that of topical estriol for treating genitourinary syndrome of menopause and to investigate the relationship between epithelial thickness and vaginal atrophy. Twenty-five menopausal women were randomized to receive either laser or estrogen treatment. Vaginal biopsies before and after treatment were compared to assess the amount and distribution of estrogen and progesterone receptors. Estrogen receptor levels were statistically similar between groups before and after treatment. Although there was no change over time in the estrogen group, an increase in receptor levels was confirmed in the laser group. Changes in estrogen receptor levels showed no association with treatment. Progesterone receptor levels were statistically similar between groups throughout treatment. There was no change over time in both groups. These changes displayed no association with the type of treatment. There was no significant correlation between epithelium thickness and estrogen or progesterone receptor levels. Estrogen and progesterone receptor levels increased and were maintained, respectively, in the vaginal epithelium in both groups. There was no significant relationship between epithelium thickness and receptor density. Laser therapy had similar outcomes to the gold standard without involving the disadvantages of hormone therapy.

Clinical and laboratory results in vaginal wall restoration using a fractional-pixel-CO2 laser: histological findings and changes in the Ki67 protein and telomere length.

Thermal deposition of laser energy in the vaginal epithelium in genitourinary syndrome of menopause (GSM) results in clinical and biological effects, but many cellular and molecular changes indicating cell proliferation or senescence inhibition are unknown. The aim of this study is to evaluate the clinical efficacy of the fractional-pixel-CO2 laser in the possible improvement of GMS signs and symptoms that can be correlated with histological changes or with cellular or molecular indicators of restoration. A detailed prospective study was designed to assess 17 women diagnosed with GSM who were treated intravaginally with two laser sessions. Seven non-treated women diagnosed with GSM were used as controls. Three validated outcome questionnaires for assessment of quality of sexual life and urinary incontinence were performed. Vaginal biopsies were collected before the first laser treatment and 4months following the second session. Histological status, elastin, collagen, and hyaluronic acid content of the biopsies were also evaluated. Cell proliferation was assessed by Ki67 staining. Telomere length (TL) was measured by qPCR. The results show an improvement of the clinical symptoms of GSM (p < 0.05), vaginal epithelium recovery and enhancement of collagen (p < 0.05), elastic fibers (p < 0.005), and hyaluronic acid (p < 0.0005) content in the lamina propria after fractional-pixel-CO2 laser treatment. The laser treatment induced a significant rise on the TL of vaginal epithelial cells (VECs), and a positive correlation was found between the improvements of the collagen and hyaluronic acid content and TL changes (r = 0.82, p < 0.05; r = 0.38, p < 0.05). The percentage of proliferative Ki67-positive VECs was increased in patients whose vaginal TL lengthened after laser treatment (p < 0.05). In conclusion, the results indicate that laser treatment may induce restoration of the vaginal epithelium which is associated to increased TL and proliferation in the VECs. Performing a TL assay could be a suitable tool to evaluate the efficacy of vaginal laser treatment.

Injection Treatments for Vulvovaginal Atrophy of Menopause: A Systematic Review.

Injection treatments have been proposed as novel treatment options for Vulvovaginal Atrophy of Menopause (VVA) also known as Genitourinary Syndrome of Menopause (GSM). However, to date data about these treatments are poor. To assess all available injection treatments for VVA. A systematic review was performed by searching five electronic databases for peer-reviewed studies that assessed injection treatments for VVA. Eight studies (7 observational and 1 randomized) with 236 women were included. Assessed injection materials were: autologous platelet-rich plasma (PRP) + hyaluronic acid (HA), not cross-linked HA plus calcium hydroxyapatite (NCLHA + CaHA), micro-fragmented adipose tissue (MFAT), hyaluronan hybrid cooperative complexes (HCC), crosslinked HA, microfat and nanofat grafting + PRP, and PRP alone. Improvement in GSM symptoms after treatment was assessed through Visual Analogic Scale (VAS) for GSM symptoms or patient satisfaction, several validated questionnaires (FSFI, VHI, FSD, SF12, ICIQ UI SF, PGI-I, FSDS-R, VSQ), symptoms severity, changes in vaginal mucosa thickness, flora, pH, and expression on vaginal mucosal biopsies of Procollagen I and III and ki67 immunofluorescence or COL1A1 and COL3A1 mRNA. Injection treatments showing significant improvement in GSM-related symptoms were: (i) HCC in terms of VAS for GSM symptoms and FSFI score; (ii) Crosslinked HA in terms of VAS for GSM symptoms, FSFI and VHI score, COL1A1 and COL3A1 mRNA expression on vaginal mucosal biopsies; (iii) NCLHA + CaHA in terms of FSFI score; (iv) PRP + HA in terms of VHI, FSD and SF12 score; (v) microfat and nanofat grafting + PRP in terms of VHI score and FSDS-R score; (vi) PRP alone in terms of VHI and VSQ scores. All assessed injection treatments except for MFAT seem to lead to significant improvement in VVA symptoms on validated questionnaires. Further studies are necessary in the field. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Next generation 3D-printed intravaginal ring for prevention of HIV and unintended pregnancy

Globally, there are 20 million adolescent girls and young women living with HIV who have limited access to long-acting, effective, women-controlled preventative methods. Additionally, although there are many contraceptive methods available, globally, half of all pregnancies remain unintended. Here we report the first 3D-printed multipurpose prevention technology (MPT) intravaginal ring (IVR) for HIV prevention and contraception. We utilized continuous liquid interface production (CLIP™) to fabricate MPT IVRs in a biocompatible silicone-based resin. Etonogestrel (ENG), ethinyl estradiol (EE), and islatravir (ISL) were loaded into the silicone poly(urethane) IVR in a controlled single step drug loading process driven by absorption. ENG/EE/ISL IVR promoted sustained release of drugs for 150 days in vitro and 14 days in sheep. There were no adverse MPT IVR-related findings of cervicovaginal toxicity or changes in vaginal biopsies or microbiome community profiles evaluated in sheep. Furthermore, ISL IVR in macaques promoted sustained release for 28 days with ISL-triphosphate levels above the established pharmacokinetic benchmark of 50–100 fmol/106 PBMCs. The ISL IVR was found to be safe and well tolerated in the macaques with no observed mucosal cytokine changes or alterations in peripheral CD4 T-cell populations. Collectively, the proposed MPT IVR has potential to expand preventative choices for young women and girls.

Efficacy of vaginal natural orifice transluminal endoscopic sentinel lymph node biopsy for endometrial cancer: a prospective multicenter cohort study.

Natural orifice transluminal endoscopic surgery (NOTES) is performed increasingly often despite the lack of high-quality evidence confirming its safety, especially for malignant diseases. The aim of this prospective study is to verify that vaginal NOTES (vNOTES) can be performed safely and effectively in early endometrial cancer staging surgery. This prospective study was conducted in two tertiary hospitals in southern China from January 2021 to May 2022. A total of 120 patients with stage I endometrial cancer were included. vNOTES or multiport laparoscopic staging surgery was selected according to each patient's wishes. The primary outcome was the sentinel lymph node detection rate, analyzed by a noninferiority test. The secondary outcomes were perioperative outcomes. Among the 120 patients enrolled, 57 underwent vNOTES, and 63 underwent multiport laparoscopy. The patient-specific detection rates of sentinel lymph nodes were 94.73 and 96.82% in the vNOTES and laparoscopy groups, respectively. Additionally, the bilateral detection rates were 82.46 and 84.13%, and the side-specific detection rates were 88.60 and 90.48% in these two groups, respectively. All three detection rates in the vNOTES group were noninferior to those of laparoscopy group at a noninferiority cutoff of -15%. The median operation times of the vNOTES and laparoscopy groups were 132.35 and 138.73min ( P =0.362), and the median estimated blood loss were 75 and 50ml ( P =0.096), respectively. No intraoperative complications occurred in either group. The pain scores on the Numerical Rating Scale at both 12h and 24h after operation were significantly lower in the vNOTES group ( P <0.001) and the median postoperative hospital stay was significantly shorter in the vNOTES group ( P =0.001). This study illustrates the potential applicability of vNOTES in gynecological malignancy surgery by demonstrating its safety and effectiveness in endometrial cancer staging. However, its long-term survival outcomes require further exploration.

Isolation of Vaginal Epithelial Cells: In Preparation of Autologous Vaginal Tissue Lining for Congenital Absence of Vagina Patients.

Infertility is a condition affecting women who are born with an underdeveloped or absent vagina, a birth defect known as congenital absence of the vagina. It is a rare disorder where the development of the Mullerian duct is obstructed by unidentified causes. The case is seldom reported due to the low prevalence and sparse epidemiology studies worldwide. A potential solution for the disorder is neovaginal creation with in vitro cultured vaginal mucosa. Limited studies have reported its application, but none are reproducible or specific regarding the established processes for acquiring vaginal epithelial cells from vaginal biopsies. These research gaps were adequately answered with an epidemiology study of inpatient details in Hospital Canselor Tuanku Muhriz, Malaysia, established methods and outcomes of vaginal tissue processing and isolation, and characterization of vaginal epithelial cells using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) and immunofluorescence assays. The reported evidence and speculation that the disorder arises because of a cellular transition event between epithelial and mesenchymal cells during the development of the Mullerian duct could be key in the creation of neovaginas using established culture procedures to improve surgical results and restore fertility.

Vaginal epithelial histology before and after fractional CO2 laser in postmenopausal women: a double-blind, sham-controlled randomized trial

Postmenopausal vaginal symptoms affect over 60% of women and may substantially impact a woman's quality of life. Since 2012, fractional CO2 laser has been suggested as a treatment for this indication. Structural assessment of vaginal epithelium using microscopic biopsy examination has been used as a primary outcome measure and surrogate determinant of success of vaginal laser in previous clinical studies. This study aimed to report the effects of laser compared with sham treatment on human vaginal epithelium from postmenopausal women using microscopic examination of tissue biopsies. This single-center double-blind, sham-controlled randomized controlled trial was performed in a tertiary hospital in Sydney, Australia. A total of 49 postmenopausal women who were symptomatic of at least 1 vaginal symptom (vaginal dryness, burning, itching; dyspareunia; or dryness) were randomized to either laser or sham treatment. For this nested histologic study, participants had a pre- and post-treatment vaginal wall biopsy collected. Biopsy samples were analyzed by 3 independent specialist gynecologic pathologists and categorized as Type 1 (well-estrogenized), 2 (poorly estrogenized), or 3 (combination) mucosae. Other outcomes assessed included symptom severity (visual analog scale for symptoms including most bothersome symptom, and Vulvovaginal Symptom Questionnaire) and Vaginal Health Index. Prespecified secondary analyses of data were performed. Categorical data were analyzed using the Pearson chi-square test (or Fisher exact test if <5 in any category) or related-samples McNemar test for paired nonparametric data. Nonparametric, continuous variables were assessed using Wilcoxon signed-rank test or Mann-Whitney U test, and parametric variables with t test or 1-way analysis of variance as appropriate. All analyses were performed using SPSS software version 26.0 (IBM Corp, Armonk, NY). There was no significant difference in microscopic features of vaginal epithelium following laser or sham treatment (P=.20). Further subgroup analyses of age, menopause type, duration of reproductive life, time since menopause and BMI, still demonstrated no significant difference between laser and sham groups in histological category of vaginal epithelium. Microscopic features at pre-treatment vaginal biopsy were Type 1 in 27% (13/49). There was no significant difference in VAS score for overall vaginal symptom between those classified as Type 1 vs. Type 2/3 (VAS score overall: Type 1 vs. Type 2/3, (48.1 [95% CI 27.0, 69.2] vs. 61.5 [95% CI 49.8, 73.3]; P=.166). Data from this double-blind, sham-controlled randomized controlled trial demonstrate that fractional CO2 laser and sham treatment have a comparable histologic effect on vaginal tissue that is not significantly different. Fractional CO2 laser is not significantly different from sham treatment and should not be recommended for clinical use for postmenopausal vaginal symptoms.

Vulvovaginal erosive lichen planus refractory to topical therapies: What's next? A case report

A 60-year-old woman was referred for progressive and severe vulvovaginal pain characterized by erosions and Wickham's stria for the past 7months. Her condition had not responded to oral fluconazole, topical estrogen cream, and topical clobetasol cream. Vulvar and vaginal biopsies were obtained under general anesthesia to verify the diagnosis of erosive lichen planus given the failed response to ultrapotent topical steroids. Tacrolimus cream was added but not tolerated. Oral and cutaneous lesions of lichen planus also developed. In the absence of evidence-based guidelines, three different systemic treatments were administered sequentially (hydroxychloroquine, mycophenolate, and finally cyclosporin) before a satisfactory, well-tolerated, and sustained clinical response was obtained. Topical betamethasone ointment in a taper was continued to assist in sustaining a vulvovaginal response after cyclosporin was discontinued.

Inflammatory invasion on human vaginal mucosa correlated with combined drug treatment and recurrence in recurrent vulvovaginal candidiasis.

Recurrent vulvovaginal candidiasis (RVVC) is a chronic, difficult to treat vaginal infection, caused by Candida species, which affects women of all ages and ethnic and social background. Most RVVC studies use animal models, and there is still a lack of observation on human tissue samples and effective therapy to reduce recurrence. We observed CD163+ macrophages and NLRP3 expression by immunohistochemistry, also investigated bacteria and fungi co-invasion by fluorescence in situ hybridization from 144 human vaginal biopsy tissues (48 RVVC, 48 VVC, 48 healthy volunteers), and we also explored the effect of combining metronidazole in the treatment of RVVC. A large number of neutrophils, lymphocytes and plasma cells infiltrated the mucosa, basement membrane and submucosa, accompanied by significantly overexpressed NLRP3 inflammasome. While CD163+ macrophages often infiltrated under the basement membrane in patients with RVVC, 29.2% of cases were found Gardnerella and fungi jointly invaded the vaginal mucosas. RVVC vaginal mucosal histopathology revealed mucosal inflammatory responses dominated by neutrophils, which may involve activation of NLRP3 and immune tolerance of M2 macrophages (CD163+ ). Fluconazole combined with metronidazole can achieve higher efficiency (95.8% vs. 70.8%) and reduce the recurrence rate more (8.3% vs. 37.5%) at 6-month follow-up. Inflammatory invasion on human vaginal mucosa correlated with combined drug treatment and recurrence in RVVC. The combined medication will need to further evaluate in future.