Impact of obesity in the identification of the sentinel lymph node in endometrial cancer: a retrospective, monocentric study and literature review.

PURPOSE: To evaluate the sentinel lymph node (SLN) protocol for staging endometrial carcinomas, assessing its impact on surgical management, and determining indications for adjuvant therapies. The study also examines factors that may influence SNL mapping, particularly focusing on the failure of the technique due to obesity. METHODS: A retrospective analysis was conducted on the medical records of patients with a histological diagnosis of endometrial carcinoma, who underwent surgical staging with SLN biopsy. The lymph node status was compared between non-obese (group 1) and obese (group 2) patients. RESULTS: 71 women were included in the study, of which 33 were non-obese (46.5%) and 38 were obese (53.5%). The failure detection rate was higher in obese patients (14, 36.8%) compared to non-obese patients (5, 15.2%) (p = 0.039). The risk of mapping failure increased by 1.6 times for every 5-unit increase in body mass index (BMI) (OR 1.672, 95% CI 1.024-2.730, p = 0.040). BMI was confirmed as an independent risk factor for mapping failure in both univariate (OR 3.267, 95% CI 1.027-10.395, p = 0.045) and multivariate analyses (OR 5.779, 95% CI 1.320-25.297, p = 0.020). CONCLUSION: SLN detection in obese patients requires great care, as obesity may alter the sensitivity of the technique.

Distension media delivery systems in hysteroscopy: past, present and future.

To examine the uterine cavity and/or to perform hysteroscopic surgery, one has to access the uterine cavity through the cervix, distend the cavity with a fluid (liquid or gas) to visualize it with a telescope and/or a camera system and use energy (mechanical or thermal) to affect and/or remove tissue. Distension of the uterine cavity then is an important component of hysteroscopy, and during the last century, numerous attempts have been made to achieve an undistorted and unobstructed panoramic view of the uterine cavity. In order to achieve this goal, the uterine cavity has been distended with fluids using a variety of techniques, including gravity-assisted systems, pressure cuffed systems, and electronic pumps. Excessive fluid intravasation during hysteroscopy can lead to significant complications, and hence, automated fluid delivery systems have been developed recently to provide a safe and more efficient method of fluid delivery. This review aims to describe the evolution of distension media delivery systems chronologically from the 1900s to the present day.

A prospective study on the diagnostic pathway of patients with stage IIIC-IV ovarian cancer: Exploratory laparoscopy (EXL) + CT scan VS. CT scan.

OBJECTIVE: To compare the diagnostic power of CT scan to a combination of exploratory laparoscopy (EXL) and CT scan in patients with stage IIIC-IV Ovarian Cancer (OC) by anatomic areas. To investigate if adding EXL to CT can reduce unnecessary laparotomy. METHODS: In the period 2009-2017, 350 consecutive patients with FIGO Stage IIIC-IV OC underwent CT and EXL prior to Visceral-Peritoneal debulking (VPD) and were included in the study. Radiologist and surgeons filled an ad-hoc form to report CT scan and EXL of eleven key anatomic areas. The decision to proceed to EXL was based on the CT scan and the decision to proceed to laparotomy (LPT) on CT and EXL. Setting LPT findings as the gold standard, positive and negative predictive value (PPV/NPV), sensitivity, specificity, and accuracy of CT, EXL and CT + EXL were calculated. We broke down the diagnostic outcomes by anatomic areas and determined the rate of unnecessary laparotomy avoided with the findings of EXL. RESULTS: Median time for the EXL was 14 min (SD +/- 3). No complication related to EXL occurred. At EXL, 325 out of 350 patients (93%) proceeded to LPT and 25 patients (7.1%) did not because of exclusion criteria. In 307 patients out of 325 (94.4%) EXL was followed by VPD. Eighteen patients had exclusion criteria found at LPT and had no VPD. EXL reduced the rate of unnecessary/futile laparotomy from 12.2% to 5.1%. CT + EXL showed a significantly higher sensitivity for all anatomic areas except for the lymph nodes. Specificity was not significantly improved. PPV was significantly improved for small bowel, porta hepatis and stomach. NPV displayed a statistical improvement in all anatomic areas except lymph nodes, stomach, and liver. CONCLUSION: The combination CT + EXL has a higher diagnostic power than CT alone, particularly on diaphragm, small bowel serosa and mesentery. The rate of unnecessary laparotomy decreased by almost 60%.

High-risk HPV-positive and -negative high-grade cervical dysplasia: Analysis of 5-year outcomes.

OBJECTIVE: To evaluate the outcomes of high-risk (HR) HPV-positive and -negative women affected by high-grade cervical dysplasia. METHODS: This is a retrospective multi-institutional study. Medical records of consecutive patients with high-grade cervical dysplasia undergoing conization between 2010 and 2014 were retrieved. All patients included had at least 5 years of follow-up. A propensity-score matching was adopted in order to reduce the presence of confounding factors between groups. Kaplan-Meir and Cox hazard models were used to estimate 5-year outcomes. RESULTS: Overall, data of 2966 women, affected by high-grade cervical dysplasia were reviewed. The study population included 1478 (85%) and 260 (15%) women affected by HR-HPV-positive and HR-HPV-negative high-grade cervical dysplasia. The prevalence of CIN2 and CIN3 among the HR-HPV-positive and -negative cohort was similar (p = 0.315). Patients with HR-HPV-positive high-grade cervical dysplasia were at higher risk of 5-year recurrence (after primary conization) that HR-HPV-negative patients (p < 0.001, log-rank test). Via multivariate analysis, HR-HPV-negative women were at low risk of recurrence (HR: 1.69 (95%CI: 1.05, 4.80); p = 0.018, Cox Hazard model). A propensity-score matched comparison was carried out in order to reduce biases that are related to the retrospective study design. In comparison to HR-HPV-negative patients, thosewith HR-HPV-positive CIN3 was associate with a 8-fold increase in the risk of recurrence (p < 0.001, log-rank test). CONCLUSIONS: HR-HPV-negative high-grade cervical dysplasia is not uncommon, accounting for 15% of our study population. Those patients experience more favorable outcomes than patients with documented HR-HPV infection(s). Further prospective studies are needed to corroborate our data.

Clear cell degeneration associated with endometriosis of abdominal wall after cesarean section: A case report and systematic review of literature.

AIM: The scar of cesarean section (CS) is the most common site of abdominal wall endometriosis (AWE), whose tumor degeneration has been reported in an increasing number of cases; the most frequent histological type is clear cell carcinoma (CCC). METHODS: We conducted a systematic research of the literature, collecting data regarding the evidence on tumor degeneration from AWE after CS. Moreover, we reported a case of clear cell borderline tumor (CCBT) originating from AWE. RESULTS: We included data of 37 patients with diagnosis of CCC. The average time between the last CS and the diagnosis of CCC was around 15 years. Overall, 26.0% and 73.9% patients received exclusive local abdominal resection of the lesion and additional surgery, respectively. Lymph nodes involvement was detected in 26.0 % patients and adjuvant chemotherapy was administered in 52.0 % cases. During follow-up period, 15.2% patients died of disease, 32.6% had no evidence of disease, and 17.4% recurred. We diagnosed a CCBT arose in a patients with AWE and a personal history of several surgical procedures for endometriosis, a CS and a subsequent transverse laparotomy. We performed an open bilateral ovariectomy and a large excision of the endometriotic abdominal lesion. CONCLUSION: Tumor degeneration from AWE seems to be a real occurrence with an increasing number of events. Considering the lack of risk factors and diagnostic instruments for tumor degeneration, the removal of AWE localization could be advisable, even though there was long average time between the trigger surgery and the tumor finding.

Current Treatment Options for Cervical Leiomyomas: A Systematic Review of Literature.

Background and objectives: Cervical leiomyomas are a rare benign disease. Although they are mainly treated surgically, currently, there is not a standardized treatment for cervical leiomyomas. This study aims to summarize current literature evidence about treatment options for cervical leiomyomas. Materials and methods: A systematic research of the literature was conducted in Scopus, PubMed/MEDLINE, ScienceDirect, and the Cochrane Library, including observational prospective and retrospective studies, case series and case reports. We collected data regarding studies related to treatment options for cervical leiomyomas, evaluating the following aspects: study design, population, treatment type, rate of surgical complications, and fertility outcome. Results: According to literature research, 38 articles were included. Among 214 patients, the weighted average age was 39.4 years-old; 23 patients were pregnant. Most of the leiomyomas (78%) were extracervical; in 22% of cases (29 patients) were intracervical; 188 patients (88%) received surgical treatment, 6 (3%) received exclusive conservative management and 21 (10%) underwent interventional radiology treatment. One hundred twenty-seven patients (67.5%) underwent myomectomy, while 54 (28.7%) and 7 (3.7%) hysterectomy and trachelectomy, respectively. Cervical myomectomy was performed by open surgery in 21 out of 127 cases (16.5%), while in 92 (72.4%) and 6 (4.7%) patients the surgical approach was performed by traditional and robot-assisted laparoscopy, respectively. The total rate of surgical complications was 5.6%. Conclusion: Surgery is the primary therapeutic option for cervical leiomyomas with a low rate of surgical complications. Interventional radiology techniques have reported promising but still limited results.

Recurrence rate after loop electrosurgical excision procedure (LEEP) and laser Conization: A 5-year follow-up study.

OBJECTIVE: Conization aims to remove pre-neoplastic lesions of the uterine cervix. Several techniques for conization have been compared, but evidence regarding the most effective therapeutic option is scant. Here, we aimed to compare the recurrence rate following laser conization and loop electrosurgical excision procedure (LEEP) in patients with high-grade cervical dysplasia (HSIL/CIN2+). METHODS: This is a retrospective multi-institutional study. Medical records of consecutive patients with HSIL/CIN2+ undergoing conization between 2010 and 2014 were retrieved. A propensity-score matching (PSM) was applied in order to reduce allocation bias. The risk of developing recurrence was estimated using Kaplan-Meir and Cox hazard models. RESULTS: Overall, 2966 patients had conization over the study period, including 567 (20%) and 2399 (80%) patients having laser conization and LEEP, respectively. Looking at predictors of recurrence, diagnosis of CIN3 (HR:3.80 (95%CI:2.01,7.21); p < 0.001) and HPV persistence (HR:1.81 (95%CI:1.11,2.96); p < 0.001) correlated with an increased risk of recurrence. After applying a PSM we selected 500 patients undergoing laser conization and 1000 undergoing LEEP. Patients undergoing LEEP were at higher risk of having positive surgical margins in comparison to patients undergoing laser conization (11.2% vs. 4.2%). The risk of having persistence of HPV was similar between the two groups (15.0% vs. 11.6%;p = 0.256). Five-year recurrence rate was 8.1% and 4% after LEEP and laser conization, respectively (p = 0.023). HPV persistence was the only factor associated with [5-]year recurrence after both laser conization (p = 0.003) and LEEP (p = 0.001). CONCLUSIONS: HPV persistence is the only factor associated with an increased risk of recurrence after either laser conization or LEEP. Owing to the lack of data regarding obstetrical outcomes, we are not able to assess the best therapeutic option for women with cervical dysplasia.

Diagnostic flow-chart to identify bowel involvement in patients with stage IIIC-IV ovarian cancer: Can laparoscopy improve the accuracy of CT scan?

OBJECTIVE: This study investigates the diagnostic power of CT scan combined with exploratory laparoscopy (EXL) at identifying large bowel involvement in patients with stage IIIC-IV primary Epithelial Ovarian Cancer (EOC) by comparing with the macroscopic surgical findings at laparotomy. METHODS: All patients with FIGO Stage IIIC-IV EOC who had Visceral Peritoneal Debulking (VPD) were included in the study. Results of CT scan, EXL and laparotomy (LPT) with regards to the bowel involvement were prospectively recorded in an ad hoc study form. Setting LPT findings as the gold standard, positive and negative predictive value (PPV/NPV), sensitivity, specificity and accuracy of CT and EXL were calculated. In addition, the diagnostic power of the combination CT scan + EXL was investigated. RESULTS: Ninety-four out of 177 patients (53.2%) had a bowel resection during VPD. CT-scan alone had sensitivity, specificity, PPV, NPV and accuracy of 56.7%, 72.4%, 70.8%, 58.5% and 63.8% respectively. EXL alone 84.4%, 93.8%, 93.8%, 84.3%, 88.8%. CT combined with EXL detected bowel involvement with a sensitivity, specificity, PPV, NPV and accuracy of 87.5%, 70.4%, 77.8%, 82.6% and 79.6% and respectively. The combined tests showed a statistically significant improvement vs. CT scan alone (p < 0001) in sensitivity, NPV and accuracy, with non-significant difference in specificity and PPV. CONCLUSIONS: CT-scan alone shows a limited diagnostic power at detecting large bowel involvement in patients with stage IIIC-IV EOC. The combination of CT scan with EXL increases the diagnostic power and enables to appropriately plan the bowel resection and consent the patients.

Use of pre-operative imaging for symptomatic uterine myomas during pregnancy: a case report and a systematic literature review.

PURPOSE: Uterine fibroids (UFs) occur in 10% of pregnancies and may lead to severe maternal-fetal complications, mainly depending on UFs characteristics and the distance to the uterine cavity (UC). When symptomatic, UFs are managed medically. Nevertheless, in about 2% of cases, surgery becomes necessary. Entry into the UC should be avoided during myomectomy. Consequentially, pre-operative assessment of this risk could be beneficial. Ultrasonography (US) represents the gold standard for UFs assessment; however, scarce evidence has been produced to assess the role of magnetic resonance imaging (MRI). The aim of the present study was to summarize current evidence about the pre-operative use of imaging techniques for UFs during pregnancy. METHODS: A systematic research of the literature was conducted in Scopus, PubMed/MEDLINE, ScienceDirect and the Cochrane Library, including case reports and case series. A case report was also discussed. We collected data regarding patients, imaging assessment, UFs characteristics, surgical information, timing and modality of delivery. RESULTS: According to our search strategy, 66 articles were selected and 210 patients were included. US assessment was reported in 36 (17%) cases. MRI was reported in 10 (4.7%) cases. Only in one case, MRI was used to measure the distance between UFs and UC. CONCLUSION: US allows an adequate pre-operative evaluation of anterior, submucosal or pedunculated symptomatic UFs in pregnancy. However, compared to US, MRI may provide a more accurate evaluation of multiple, large, intramural or posterior UFs and could measure the distance between UFs and UC more accurately.

Management of endometrial, ovarian and cervical cancer in the elderly: current approach to a challenging condition.

PURPOSE: Gynaecological cancer management in older people represents a current challenge. Therefore, in the present paper, we aimed to gather all the evidence reported in the literature concerning gynecological cancers in the elderly, illustrating the state of art and the future perspectives. METHODS: We searched MEDLINE (PubMed), EMBASE, Cochrane Central Register of Controlled Trials, IBECS, BIOSIS, Web of Science, SCOPUS and Grey literature (Google Scholar; British Library) from January 1952 to May 2017, using the terms "ovarian cancer", "endometrial cancer", "cervical cancer", "gynecological cancers" combined with 'elderly', 'cancer', 'clinical trial' and 'geriatric assessment'. RESULTS: The search identified 81 citations, of which 65 were potentially relevant after initial evaluation and met the criteria for inclusion and were analyzed. We divided all included studies into three different issue: "Endometrial cancer", "Ovarian cancer" and "Cervical cancer". CONCLUSIONS: The present literature review shows that, in spite of the higher burden of comorbidities, elderly patients can also benefit from standard treatment to manage their gynecological cancers. It is important to overcome the common habit of undertreating the elderly patients because they are more fragile and with a lower life expectancy than their younger counterpart. Further trials with elderly women are warranted.

Benign multicystic mesothelioma and peritoneal inclusion cysts: are they the same clinical and histopathological entities? A systematic review to find an evidence-based management.

PURPOSE: Peritoneal mesothelial cysts (PMC) are a clinical dilemma because of their true pathogenic nature. Many definitions have been associated with PMC, including "benign multicystic mesothelioma", "cystic mesothelioma", "multilocular peritoneal inclusion cysts", ''inflammatory cysts of the peritoneum" or "postoperative peritoneal cyst". METHODS: We herein performed a systematic review of the literature focusing on clinical and histopathological aspects of PMC, diagnosis, and therapies. Moreover, we described our experience with a case of PMC in a young female. RESULTS: Since there is often a history of prior surgery or inflammatory disease, most authors consider PMC of reactive origin. However, in some cases they occur without any documentable signs of disease or injury. A variety of clinical findings can complicate the preoperative assessment and a multitude of histological pictures may potentially lead to a misdiagnosis. The absence of a uniform treatment strategy and lack of long-term follow-up often hinder the accurate definition leading to unnecessary or unnecessarily aggressive therapy. CONCLUSIONS: PMC are more common than had previously been thought. Most authors consider them non-neoplastic; thus the designation of "peritoneal inclusion cyst" is preferable. The term "mesothelioma" should be used only in cases of histological evidences of atypia. The high rates of recurrence suggest that the goal of treatment should not be necessarily complete eradication, but symptomatic relief through individualized treatment. This is a topic of particular importance, especially in young female where recurrence rates could be lower than those reported in adults and where an improperly aggressive treatment could have repercussions on fertility.

Etiology, pathophysiology and biomarkers of interstitial cystitis/painful bladder syndrome.

PURPOSE: Interstitial cystitis/painful bladder syndrome (IC/PBS) is a chronic pain syndrome and a chronic inflammatory condition prevalent in women that leads to urgency, sleep disruption, nocturia and pain in the pelvic area, to the detriment of the sufferer's quality of life. The aim of this review is to highlight the newest diagnostic strategies and potential therapeutic techniques. METHODS: A comprehensive literature review was performed on MEDLINE, PubMed, and Cochrane databases gathering all literature about "Interstitial cystitis" and "Painful Bladder Syndrome". Visual analogue scales, epidemiological strategies, pain questionnaires and similar techniques were not included in this literature survey. RESULTS: The etiology, exact diagnosis and epidemiology of IC/PBS are still not clearly understood. To date, its prevalence is estimated to be in the range of 45 per 100,000 women and 8 per 100,000 men, whereas joint prevalence in both sexes is 10.6 cases per 100,000. There are no "gold standards" in the diagnosis or detection of IC/PBS, therefore, several etiological theories were investigated, such as permeability, glycosaminoglycans, mast cell, infection and neuroendocrine theory to find new diagnostic strategies and potential biomarkers. CONCLUSION: Due to the fact that this disease is of an intricate nature, and that many of its symptoms overlap with other concomitant diseases, it could be suggested to classify the patients with emphasis on the phenotype, as well as their symptom clusters, to tailor the diagnostic and management choices according to the observed biomarkers.

Target Therapies for Uterine Carcinosarcomas: Current Evidence and Future Perspectives.

Carcinosarcomas (CS) in gynecology are very infrequent and represent only 2-5% of uterine cancers. Despite surgical cytoreduction and subsequent chemotherapy being the primary treatment for uterine CS, the overall five-year survival rate is 30 ± 9% and recurrence is extremely common (50-80%). Due to the poor prognosis of CS, new strategies have been developed in the last few decades, targeting known dysfunctional molecular pathways for immunotherapy. In this paper, we aimed to gather the available evidence on the latest therapies for the treatment of CS. We performed a systematic review using the terms "uterine carcinosarcoma", "uterine Malignant Mixed Müllerian Tumors", "target therapies", "angiogenesis therapy", "cancer stem cell therapy", "prognostic biomarker", and "novel antibody-drug". Based on our results, the differential expression and accessibility of epithelial cell adhesion molecule-1 on metastatic/chemotherapy-resistant CS cells in comparison to normal tissues and Human Epidermal Growth Factor Receptor 2 (HER2) open up new possibilities in the field of target therapy. Nevertheless, future investigations are needed to clarify the impact of these new therapies on survival rate and medium-/long-term outcomes.

Biocompatible porcine dermis graft to treat severe cystocele: impact on quality of life and sexuality.

PURPOSE: To study the quality of life (QoL) and sexual function changes of women affected by severe cystocele treated using biocompatible porcine dermis graft. METHODS: 20 women (ranging in age from 47 to 71 years, mean age 58.7) with third- and fourth-degree cystocele (according to Baden and Walker classification) were enrolled. The Short Form-36 questionnaire to assess QoL was administrated at baseline and 12 months after surgical treatment. The Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire (PISQ-12) to measure the changes of sexual behavior was used at baseline and 12 months after surgical treatment. Each woman underwent translabial color Doppler ultrasonography to measure the clitoral blood flow before and 12 months after surgical treatment. RESULTS: Women reported QoL improvement (P < 0.001). By PISQ-12, improvement of the behavioral emotive factor score, the physical factor score, the partner-related factor score and of the total score during the 12-month follow-up with respect to baseline experience was observed (P < 0.001). Color Doppler measurement showed that the mean pulsatility index, peak systolic velocity, resistance index and end-diastolic velocity of clitoral arteries did not significantly change (P = NS). CONCLUSIONS: Biocompatible porcine dermis graft to treat severe cystocele considerably improves QoL and sexual function, and does not influence clitoral blood flow. Our data could add new information about sexual behavior after prolapse treatment using this kind of graft, particularly about the impact on clitoral blood flow changes.

Cervical Intraepithelial Neoplasia Grade 3 (CIN3) in Women Younger than 30 Years Was Significantly Associated with HPV16/18 Genotypes.

BACKGROUND: The objective of the present study is to investigate the age-specific distribution of HPV genotypes in CIN3 lesions in screened unvaccinated women. These data are essential to optimize current and future screening programs. METHODS: A multicenter retrospective study was conducted. A total of 408 unvaccinated women with positive histology and a high-risk HPV genotype were enrolled. Each woman at baseline had HPV DNA testing and HPV genotyping, and all women underwent targeted biopsy and/or treatment with a loop electrosurgical excision procedure (LEEP) before entering the study. We divided the genotypes into HPV16/18 and HPV non-16/18 (HPV31/33/45/35/39/51/52/58/59/66/68). Women were divided into increasing age categories: <30, 30-44, and ≥45. RESULTS: The percentage of CIN3 associated with HPV16/18 is maximum in women under 30 years of age (85.1%), drops to 75.6% in women aged between 30 and 44 years, and up to 47.2% in women over 45 years. CIN3 in women younger than 30 years was significantly associated with HPV16/18 genotypes (p = 0). DISCUSSION: The data from the present study suggest that the risk of CIN3 is related to the woman's age and hr HPV genotype. The data highlight two different types of CIN3: a more frequent type, related to HPV16/18, which develops rapidly and in young women, and another, relating to non-16/18 HPV, which develops later at an advanced age and slowly, through low-grade lesions.

Vaginal Intraepithelial Neoplasia (VaIN) after Hysterectomy Is Strongly Associated with Persistent HR-HPV Infection.

The data from the literature show that women undergoing a LEEP due to CIN3 have a greater risk of having subsequent high-grade anogenital intraepithelial neoplasia or cancer, and the risk is greater for vaginal cancer than for anal and vulvar cancers. It is hypothesized that the laparoscopic hysterectomy procedure may cause a higher incidence of VaIN in hysterectomized women. There are few studies addressing this issue, and they show mixed results. This study aimed to investigate the incidence of high-grade or severe VaIN in the population of women undergoing hysterectomy for CIN3 or benign uterine disease and illustrate the treatment options and follow-up. METHODS: This retrospective study was conducted on 170 women who underwent a laparoscopic hysterectomy due to high-grade cervical intraepithelial neoplasia (CIN3) or benign gynecological disease. The follow-up strategy included performing a cotest and colposcopy with biopsy if necessary. The median time between primary treatment and a diagnosis of high-grade VaIN was 18 months. RESULTS: High-grade or severe VaIN was found in eight patients after hysterectomy (4.7%). All cases of high-grade VaIN occurred in women with persistent HPV infection. The most frequent genotype was 16. Women hysterectomized due to CIN3 showed an eight-fold greater risk than women hysterectomized due to benign disease of developing high-grade VaIN. The risk of VaIN is low in women hysterectomized due to benign disease. The risk of developing VaIN is greater in women with viral persistence. CONCLUSION: All these elements suggest that it is a history of HPV-related disease of the lower genital tract and viral persistence, rather than hysterectomy itself, that should be considered risk factors for the development of high-grade VaIN. After hysterectomy, patients with a history of CIN should undergo annual screening with vaginal dome cytology and HPV testing.

Stage II endometrial cancer: The diagnostic power of hysteroscopic excisional biopsy and MRI in the pre-operative cervical stroma assessment.

INTRODUCTION/BACKGROUND: Stage II Endometrial cancer (EC) accounts only for 12% of cases. Recent evidences redraw the weight of radicality in this stage as it would seem to have no impact on survival outcomes claiming for radicality when free surgical margins are not ensured to be achieved by simple hysterectomy. Thus, an accurate pre-operative evaluation might be crucial. This study aims to estimate the diagnostic power of Hysteroscopic excisional biopsy (HEB) of cervical stroma alone and combined with Magnetic resonance imaging (MRI) to predict the stage and concealed parametrial invasion in patients with preoperative stage II EC. METHODOLOGY: From January 2019 to November 2023, all patients evaluated at the Department of Gynaecology Oncology of Humanitas, Istituto Clinico Catanese, Catania, Italy, with a diagnosis of EC and evidence of cervical stromal diffusion on preoperative MRI and/or office hysteroscopy evaluation, considered suitable for laparoscopic modified type B hysterectomy, were consecutively included in the study. These underwent endometrial and cervical hysteroscopy excisional biopsy (HEB) for histological evaluation before definitive surgery. The data obtained were compared with the definitive histological examination (reference standard). RESULTS: Sixteen patients met the including/excluding criteria and were considered into the study. Stage II endometrial cancer were confirmed in 3 cases (18.7%). We reported 2 (12,5%) parametrial involvement (IIIB), 4 (25%) cases of lymph nodes metastasis (IIIc), 7 (43,7%) cases of I stage. MRI had a sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy (95% CIs) of 71%, 44%, 50%, 66% and 56.2 % respectively. HEB showed sensitivity, specificity, PPV, NPV and accuracy (95 % CI) of 85 %, 89 %, 85 %, 88 % and 87 % respectively. Comparing HEB + MRI to HEB alone, no statistical differences were noted in all fields. Considering parametrial invasion, MRI had better sensitivity but there were no statistical differences to HEB in other fields, showing both a worthy NPV. CONCLUSION: HEB was accurate in all fields for cervical stroma assessment and had a fine NPV to exclude massive cervical involvement up to parametrial. Considering the new FIGO staging a preoperative molecular and histological evaluation of the cervical stroma may be useful. Operative hysteroscopy seems to be a feasible and accurate method for this purpose.

Extended Genotyping to Stratify the Risk of CIN2+ in Women with Persistent HPV Infection, Negative Cytology and Type 3 Transformation Zone.

Persistent human papillomavirus (HPV) infection is recognized as a major risk factor for cervical cancer. Women with persistent HPV and negative cytology are at greater risk of CIN2+ than women with negative infection. The diagnosis becomes more complicated when the woman has a type 3 transformation zone at colposcopy. The aim of this study was to determine the prevalence of CIN2+ in women with persistent HPV, negative cytology and TZ3; how to stratify the risk of CIN2+; and what the best diagnostic strategy is, given TZ3. METHODS: In a multicenter retrospective cohort study, we enrolled women with negative cytology and TZ3 among the 213 women referred for colposcopy for persistent HPV. The average age of the women was 53 years; in particular, 83% were postmenopausal women. In the presence of a TZ3, the entire transformation zone cannot be explored, making colposcopy and targeted biopsy useless and inadequate, with great risks of underdiagnosis or missed diagnosis. Women with TZ3 underwent diagnostic LEEP to ensure correct diagnoses. RESULTS: The study highlighted 19% (16/84) of CIN2+ lesions, a higher frequency of non-HPV 16/18 genotypes (76.2%), and 50% of CIN2+ lesions being due to non-HPV 16/18 genotypes. Furthermore, more than half of the women (80.9%) had normal histopathological results in the LEEP sample. CONCLUSION: Women with viral persistence, negative cytology, and TZ3 have a 19% risk of CIN2+; genotyping helps stratify risk, but extensive genotyping is necessary instead of partial genotyping (16/18), referring to a population of women over 50 years old in which the prevalence of genotypes 16,18 decreases and the prevalence of other genotypes increases; diagnostic LEEP is excessive (only 16 cases of CIN2+ out of 48 cases treated), even though 83% of women had viral clearance after LEEP; p16/Ki67 double staining could be a potential risk marker, which would only highlight women at risk of CIN2+ to undergo LEEP. To individualize the diagnostic workup and treatment and minimize the risk of under diagnosis and overtreatment, future studies should explore the use of extended genotyping and new biomarkers for individual risk stratification.

Correlation of the HPV 16 Genotype Persistence in Women Undergoing LEEP for CIN3 with the Risk of CIN2+ Relapses in the First 18 Months of Follow-Up: A Multicenter Retrospective Study.

OBJECTIVE: Specific hr-HPV genotypes have different natural histories and different oncogenic capacity. This study aimed to investigate the risk of CIN2+ recurrence of the individual genotypes and evaluate how the duration of HPV persistence influences the risk of developing recurrent 16 cervical dysplasia of high grade (CIN2+). METHODS: Data from patients with persistent HPV infection after primary conization were retrospectively extracted. Kaplan-Meier proportional hazards models were used to evaluate associations between the duration of HPV persistence and the risk of developing recurrent CIN2+. Kruskal-Wallis testing with Dunn's multiple comparison test was used to test whether there was a statistically significant difference in the time to development of tumor recurrences between different genotypes. RESULTS: Overall, 333 patients met the inclusion criteria. In 285 cases the HPV infection was persistent, in 48 cases (18%) it was transient, i.e., different genotypes after LEEP. Overall were diagnosed 39 relapses (13.7%), 79.5% (31/39 cases) were due to genotype 16, 20.5% (8/39) were linked to the other genotypes. Persistence of genotype 16 showed a 7-fold increased risk of developing a CIN2+ relapse, OR = 7.08 (95%CI: 3.12-16.08). Furthermore, the majority of relapses (38/39) occurred within 24 months of persistence with a cut-off represented by 18 months (p = 0.001) in which the relapse rate is maximum and the most frequently found genotype was the 16th with 31 (79.5%) cases of recurrence. Kruskal-Wallis test with Dunn's multiple comparisons has shown statistically significant difference in the time of development of CIN2 relapses among HPV16 and other genotypes. (p < 0.05). Kaplan-meier analysis has shown statistically significant difference between the time to CIN2+ relapse onset in patients with HPV 16 infection and patients with other hrHPV genotypes. (p < 0.05) Conclusions: the study results suggest that persistent HPV infection after LEEP with the same HR genotype present before surgery represents one of the most important predictive factors of the risk of CIN2+ recurrence. The persistence of HPV16 for the first 18 months strongly correlates with the risk of developing a CIN2+ recurrence.

The Coexistence of Cervical Intraepithelial Neoplasia (CIN3) and Adenocarcinoma In Situ (AIS) in LEEP Excisions Performed for CIN3.

The purpose of this study was to evaluate the incidence of AIS and AC in the histological cone of women treated for CIN3. Furthermore, through the study of the specific HR HPV genotypes, we obtained more information on the possible different nature between the single CIN3 lesion and the CIN3 coexisting with the glandular lesion. METHODS: A sample of 414 women underwent LEEP for CIN3. The study sample consisted of 370 women with a CIN3 lesion alone and 44 women with a CIN3 lesion coexisting with AIS or adenocarcinoma. We studied the individual HR HPV genotypes and their frequency in the two groups under study. Furthermore, the therapeutic results and follow-ups for the population were studied on the entire study sample. RESULTS: In patients with a single CIN3 lesion, 11 high-risk genotypes were detected; in patients with CIN3 associated with AIS or AC, only 4 different genotypes were detected (16, 18, 45, 33). Overall, the frequency of HPV 18 was significantly higher in CIN3 coexisting with AIS compared to solitary CIN3 lesions, χ2 = 27.73 (p < 0.001), while the frequency of other high-risk genotypes was significantly higher in patients with a single CIN3 than in patients with CIN3 coexisting with AIS. In our study population, mixed lesions (CIN3 coexisting with AIS), unlike their squamous counterparts (single CIN3 lesions), were characterized by skip lesions, which demonstrate more aggressive behavior and a higher rate of viral persistence and recurrence. CONCLUSION: A relatively high rate (10.7%) of AIS-AC was found in women treated for CIN3. Our study confirms the multifocal biological nature of the CIN3 lesion coexisting with AIS compared to the single CIN3 lesion. All this justifies the different treatments to which CIN3 lesions coexisting with AIS are addressed; in fact, the latter are treated with hysterectomy, while CIN3 is treated with conization alone.