A Longitudinal Multiinstitutional Study of Vulvar Lichen Sclerosus: From Childhood to Perimenopause.

OBJECTIVE: The main outcome of this study was the evaluation of clinical characteristics, comorbidities, and therapeutic approaches in patients with vulvar lichen sclerosus (VLS) aged from childhood to perimenopause. Secondly, it was intended to compare these characteristics according to the menarchal status. METHODS: Patients less than 45 years of age with a diagnosis of VLS from January 2002 to June 2022 in 10 referral centers were included in this retrospective longitudinal study. The univariate analysis compared the dependent variables according to menarchal status. RESULTS: One hundred eighty-six patients met the inclusion criteria. At diagnosis, between 25% and 40% of premenarchal patients reported signs related to subepithelial hemorrhage. A significantly greater presence of bleeding ( p < .005), easy bruising ( p = .028), fissures ( p = .008), petechiae/splinter hemorrhages ( p < .001), and bleeding/blistering or open sores ( p = .011) was observed in premenarchal patients with respect to the postmenarchal group. The perineum ( p = .013) and the perianal region ( p < .001) were significantly more involved in the premenarchal group. Topical calcineurin inhibitors were more used in the premenarchal population ( p = .004), whereas vitamin E oil and moisturizers were more used in the postmenarchal population ( p = .047). CONCLUSIONS: Vulvar lichen sclerosus is a chronic condition that can cause vulvar changes that result in severe morbidity and affects sexual function and quality of life, even before menopause. Vulvar lichen sclerosus continues to be misdiagnosed in this population. This may lead to an average delay from symptom onset to diagnosis. Evaluating clinical manifestations of VLS in premenarchal and postmenarchal age allowed us to find different clinical characteristics between the 2 periods suggestive of the diagnosis.

Clinical validation of full HR-HPV genotyping HPV Selfy assay according to the international guidelines for HPV test requirements for cervical cancer screening on clinician-collected and self-collected samples.

BACKGROUND: According to international guidelines, Human Papillomavirus (HPV) DNA tests represent a valid alternative to Pap Test for primary cervical cancer screening, provided that they guarantee balanced clinical sensitivity and specificity for cervical intraepithelial neoplasia grade 2 or more (CIN2+) lesions. The study aimed to assess whether HPV Selfy (Ulisse BioMed - Trieste, Italy), a full-genotyping HPV DNA test that detects and differentiates 14 high-risk HPV (HR-HPV) types, meets the criteria for primary cervical cancer screening described in the international guidelines, on clinician-collected as well as on self-collected samples. METHODS: For each participant woman, consecutively referring to Azienda Sanitaria Universitaria Giuliano Isontina (Trieste, Italy) and CRO-National Cancer Institute (Aviano, Italy) for the cervical cancer screening program, the following samples were tested: (a) a clinician-collected cervical specimen, analyzed with the reference test (Hybrid Capture®2 test, HC2) and HPV Selfy; and (b) a self-collected vaginal sample, analyzed with HPV Selfy. Enrolled women were also asked to fulfill a questionnaire about self-sampling acceptability. As required by guidelines, a non-inferiority test was conducted to compare the clinical performance of the test under evaluation with its reference test. RESULTS: HPV Selfy clinical sensitivity and specificity resulted non-inferior to those of HC2. By analysis of a total of 889 cervical liquid-based cytology samples from a screening population, of which 98 were from women with CIN2+, HPV Selfy showed relative sensitivity and specificity for CIN2+ of 0.98 and 1.00 respectively (non-inferiority score test: P = 0.01747 and P = 0.00414, respectively); the test reached adequate intra- and inter-laboratory reproducibility. Moreover, we demonstrated that the performance of HPV Selfy on self-collected vaginal samples was non-inferior to the performance obtained on clinician-collected cervical specimen (0.92 relative sensitivity and 0.97 relative specificity). Finally, through HPV Selfy genotyping, we were able to describe HPV types prevalence in the study population. CONCLUSIONS: HPV Selfy fulfills all the requirements of the international Meijer's guidelines and has been clinically validated for primary cervical cancer screening purposes. Moreover, HPV Selfy has also been validated for self-sampling according to VALHUDES guidelines. Therefore, at date, HPV Selfy is the only full-genotyping test validated both for screening purposes and for self-sampling. Trial registration ASUGI Trieste n. 16008/2018; CRO Aviano n.17149/2018.

Spotlight on the role of human papillomavirus vaccines.

In high income setting, the massive implementation of screening programs has reduced the incidence of cervical cancer, dramatically. However, cervical cancer still remains a major health concern, being one of the most common cause of death for cancer among women. The adoption of primary prevention through vaccination against HPV aims to reduce the prevalence of HPV-related lesions and cervical cancer. Accumulating data highlighted the cost-effectiveness of introducing HPV vaccination for adolescent and young adults. In the present review, we critically evaluated the role of vaccination against HPV, focusing much more on the role of vaccination in specific cluster of subjects (eg, post-treatment and older adults). Additionally, we evaluated the available evidence on the role of vaccination in HIV-positive subjects and in women receiving solid organs transplantation. We observed that although vaccination might be considered effective in those cluster of subjects; further evidence is needed to assess the cost-effectiveness of vaccination in these settings.

Human epidermal growth factor receptor-2 (HER2) is a potential therapeutic target in extramammary Paget's disease of the vulva.

BACKGROUND: Invasive vulvar Paget's disease with over-expression of the human epidermal growth factor receptor 2 (HER2) protein is potentially suitable for targeted therapy, especially in a metastatic setting where no effective treatments are available. METHODS: Four consecutive patients with HER2 positive advanced vulvar Paget's disease, treated with weekly trastuzumab (loading dose 4 mg/kg, then 2 mg/kg) and paclitaxel (80 mg/m2) followed by 3-weekly trastuzumab maintenance (6 mg/kg), are reported. RESULTS: Median age and follow-up of patients were 62.5 years (45-74) and 16 months (6-54), respectively. Complete or partial responses were observed in all patients. Median time to response was 3 months (range 2-4), while median duration of response was 10 months (range 2-34). Case 1 presented with pulmonary and lymph nodes involvement. She experienced a radiological complete response after 24 treatment administrations, and a progression-free survival of 36 months. At disease progression, treatment re-challenge achieved partial response. She is currently receiving treatment with trastuzumab-emtansine. Case 2 was a 74-year-old woman who developed pulmonary metastasis after first-line cisplatin treatment. She had a partial response and a progression-free survival of 10 months. Case 3 had inguinal and para-aortic lymphadenopathy in complete response after 18 treatment administrations. She developed brain metastasis while receiving trastuzumab maintenance. Case 4 was treated for locally advanced disease and experienced a subjective benefit with relief in perineal pain and itching. No unexpected treatment-related side effects were reported. CONCLUSIONS: Advanced vulvar Paget's disease is a rare disorder and no standard treatment is available. In the sub-group of HER2 positive disease, weekly paclitaxel-trastuzumab appears to be active and safe, and may be considered a therapeutic option in these patients.

Clinical Characteristics and Long-Term Follow-up of Patients Treated for High-Grade Vaginal Intraepithelial Neoplasia: Results From a 20-Year Survey in Italy.

OBJECTIVES: The aim of this survey was to evaluate the different surgical approaches for women with high-grade vaginal intraepithelial neoplasia (HG-VaIN) used in 8 hospitals in central and northern Italy in the last 20 years. In particular, the baseline characteristics of the patients and factors potentially leading to excisional treatment rather than ablation were considered. Moreover, the clinical outcome of patients treated for HG-VaIN (disease persistence or recurrence and progression toward invasive vaginal cancer) was analyzed. MATERIALS AND METHODS: The medical records of all women initially diagnosed with HG-VaIN and subsequently treated in 8 Italian hospitals from January 1996 to December 2016 were analyzed in a multicenter retrospective case series. RESULTS: Among the 226 women included, 116 (51.3%) underwent ablative procedures and 110 underwent excisional surgery (48.7%). An ablative procedure was preferred in cases where multiple lesions were found on colposcopic examinations. Physicians decided more frequently to perform excisional procedures in women with menopausal status, high-grade referral cervical cytology, previous hysterectomy for human papillomavirus-related disease, or VaIN 3 on colposcopic-guided biopsy. CONCLUSIONS: The surgical treatment of HG-VaIN should be tailored according to the clinical characteristics of each woman and each lesion. However, in potentially high-risk cases (VaIN 3, previous hysterectomy for human papillomavirus-related disease, and menopausal women) or in those cases in which an occult invasive disease cannot be ruled out, an excisional approach should be preferred.In any case, long-term follow-up is advisable in women treated for HG-VaIN.

Factors Related to Overtreatment in the See-and-Treat Approach: A Retrospective Multicentric Observational Study.

OBJECTIVE: The aim of the study was to evaluate the association between colposcopic features, age, menopausal status, and overtreatment in women subjected to "see-and-treat" approach, to identify subgroups of patients in which this approach could be more appropriate. MATERIALS AND METHODS: Retrospective multicentric cohort study conducted on women older than 25 years, with a high-grade squamous cytological report and a visible squamocolumnar junction, in which colposcopy and the excisional procedure were performed at the same time without a previous cervical biopsy (see and treat). Overtreatment was defined as histopathological finding of cervical intraepithelial lesion grade 1 or normal tissue. RESULTS: Among the 254 included patients, the overall overtreatment rate was 12.6%, whereas in women with a grade 2 colposcopy, it was 3.2% and, in women with grade 1 colposcopy, it was 22.0%. Among the considered factors (age, menopause, and grade 1 colposcopy), only a positive association with overtreatment and grade 1 colposcopy emerged (odds ratio = 8.70, 95% CI = 2.95-25.62, p < .001). CONCLUSIONS: See and treat may be appropriate in women older than 25 years with a visible squamocolumnar junction and a high-grade squamous cervical cytology. Patients need to be informed about the higher risk of overtreatment in case of a grade 1 colposcopic impression, which however may still be considered acceptable. Patient's age and menopausal status should not influence the decision to propose a see-and-treat approach.

Number of Nodes Removed With Inguinofemoral Lymphadenectomy and Risk of Isolated Groin Recurrence in Women With FIGO Stage IB-II Squamous Cell Vulvar Cancer.

AIM: The aim of this study was to evaluate if the lymph node count from inguinofemoral lymphadenectomy impacted the risk of isolated groin recurrence in patients with node-negative squamous cell vulvar cancer. MATERIALS AND METHODS: This is a retrospective cohort study of women with squamous cell vulvar cancer (stage IB-II according to the 2009 Revised International Federation of Gynecology and Obstetrics staging system) who underwent primary radical vulvar surgery and groin lymphadenectomy between January 2005 and December 2014. Patients' sociodemographic characteristics, the disease characteristics, the number of nodes removed from each groin, and the oncologic outcome were evaluated. A cutoff value of at least 6 nodes removed from each groin was used to define the adequacy of inguinofemoral dissection. RESULTS: Seventy-six patients, fulfilling the study inclusion criteria, were considered. The mean number of nodes removed (bilaterally) was 14.5 (±5.3, SD), with a range of 2 to 29 nodes. Thirty-three women (43.4%) had less than 6 nodes removed from each groin. In the whole study cohort, 4 cases of isolated groin recurrence (5.3%) were detected, and all these recurrences developed in patients with less than 6 nodes removed. Considering the demographic, clinical, and histopathological characteristics potentially related to the risk of groin recurrence, only the number of nodes removed showed a significant correlation. CONCLUSIONS: Women treated for vulvar cancer in which less than 6 nodes are removed from each groin are at higher risk of groin recurrence.

Primary intestinal-type adenocarcinoma of the vulva. A case report and review of the literature.

Background: Primary non-squamous cell carcinomas of the vulva are rare entities including various tumor types. Among these, primary vulvar intestinal-type adenocarcinoma (vPITA) is extremely rare. Until 2021, less than twenty-five cases have been reported in the literature. Case presentation: We report a case of vPITA in a 63 years old woman with a histopathological diagnosis of signet-ring cell intestinal type adenocarcinoma at vulvar biopsy. Accurate clinical and pathological work-up excluded secondary metastatic localization, and vPITA was diagnosed. The patient was treated with radical vulvectomy and bilateral inguinofemoral dissection. Adjuvant chemo-radiotherapy was performed because of a positive lymph node. At 20 months follow-up the patient was alive and free of disease. Conclusion:  The prognosis of this very rare disease is unclear and optimal treatment is not well established. About 40% of clinical early-stage diseases reported in literature had positive inguinal nodes, more than in vulvar squamous cell carcinomas. A proper histopathologic and clinical diagnosis is mandatory to exclude secondary disease and to recommend an adequate treatment.

Extramammary Paget's Disease of the Vulva and Concomitant Premalignant/Malignant Vulvar Lesions: A Potential Challenge in Diagnosis and Treatment.

The aim of the present study was to evaluate the incidence of concomitant vulvar cancers or premalignant lesions in women surgically treated for extramammary Paget's disease of the vulva (EMPDV) through a multicenter case series. The medical records of all women diagnosed with and treated for EMPDV from January 2010 to December 2020 were retrospectively analyzed. Women with EMPDV and synchronous vulvar cancer, vulvar intraepithelial neoplasia (VIN) and/or lichen sclerosus (LS) at the histology report were included in the study. A total of 69 women eligible for the present study were considered. Concomitant vulvar lesions occurred in 22 cases (31.9%). A total of 11 cases of synchronous VIN (50%) and 14 cases (63.6%) of concomitant LS were observed. One patient (4.5%) had synchronous vulvar SCC (FIGO stage 1B). Women with EMPDV and concomitant premalignant/malignant vulvar lesions had a significantly higher rate of invasive EMPDV and wider lesions with an extravulvar involvement. The specific meaning of the association between EMPDV, VIN, SCC and LS remains unclear. The potential overlapping features between different vulvar lesions highlight the importance of dedicated gynecologists and pathologists in referral centers.

Concurrent Endometrial Cancer in Women with Atypical Endometrial Hyperplasia: What Is the Predictive Value of Patient Characteristics?

BACKGROUND: The rate of concurrent endometrial cancer (EC) in atypical endometrial hyperplasia (AEH) can be as high as 40%. Some patient characteristics showed associations with this occurrence. However, their real predictive power with related validation has yet to be discovered. The present study aimed to assess the performance of various models based on patient characteristics in predicting EC in women with AEH. METHODS: This is a retrospective multi-institutional study including women with AEH undergoing definitive surgery. The women were divided according to the final histology (EC vs. no-EC). The available cases were divided into a training and validation set. Using k-fold cross-validation, we built many predictive models, including regressions and artificial neural networks (ANN). RESULTS: A total of 193/629 women (30.7%) showed EC at hysterectomy. A total of 26/193 (13.4%) women showed high-risk EC. Regression and ANN models showed a prediction performance with a mean area under the curve of 0.65 and 0.75 on the validation set, respectively. Among the best prediction models, the most recurrent patient characteristics were age, body mass index, Lynch syndrome, diabetes, and previous breast cancer. None of these independent variables showed associations with high-risk diseases in women with EC. CONCLUSIONS: Patient characteristics did not show satisfactory performance in predicting EC in AEH. Risk stratification in AEH based mainly on patient characteristics may be clinically unsuitable.

Histopathological findings in hysterectomy for cervical stenosis in postmenopausal women: A retrospective case series.

OBJECTIVE: To analyze the histopathological findings in postmenopausal women who underwent hysterectomy for postsurgical cervical stenosis, evaluating the incidental findings of preinvasive or invasive uterine and cervical disease. METHODS: Retrospective case series of postmenopausal women who underwent hysterectomy for postsurgical cervical stenosis at Gynecological Oncology Unit of Istituto di Ricovero e Cura a Carattere Scientifico Centro di Riferimento Oncologico Aviano-National Cancer Institute from January 2014 to January 2021. RESULTS: During the study period, 36 women underwent hysterectomy for postsurgical cervical stenosis at our institution. Cervical stenosis occurred 10.2 ± 5.6 years from the onset of menopause. In particular, 26 (72.2%) patients underwent a single loop electrosurgical excision procedure or carbon dioxide (CO2)-laser conization before the onset of stenosis. The remaining 10 (27.8%) women had multiple surgical excision before the onset of stenosis. At the final histopathological analysis, 17 (47.2%) patients had a preinvasive or invasive gynecological disease. In particular, 9 cases of cervical disease (including 1 case of endocervical squamous cell carcinoma pT1a) and 6 cases of endometrial hyperplasia emerged. Also, 2 cases of tubo-ovarian diseases were found. CONCLUSIONS: Postsurgical cervical stenosis is a challenging clinical condition, especially in women treated for cervical intraepithelial neoplasia or microinvasive cervical cancer. As shown, cervical stenosis can prevent an adequate gynecological follow-up and a prompt diagnosis of malignancies. Therefore, postmenopausal women with cervical stenosis should be carefully counseled, and hysterectomy could be a reasonable option, especially in those cases in which a conservative approach is not feasible, failed, or is not accepted by the patient.

CIN2 in childbearing-age women: may colposcopy help choosing the proper management?

BACKGROUND: CIN2 is considered a biologically equivocal lesion falling between low- and high-grade cervical dysplasia, but it is often managed with cervical conization as a high-grade lesion. However, since cervical conization can lead to an increased risk of adverse obstetric events, it might be interesting to identify, by colposcopy, a subgroup of women with a low risk of "occult" CIN3 who could be managed with a "wait and see" approach. METHODS: All the women with CIN2 cervical biopsy from 1999 to 2019 were retrospectively identified. Their colposcopic patterns at the time of biopsy and the histopathological findings on the final cone specimen were compared. RESULTS: Among the 354 women with CIN2 biopsy included, the overall CIN3+ lesion rate on final cone specimen was 21.4%. The rate of CIN3 on final specimen was higher in women with G2 colposcopy compared to G1 (27.2% vs. 15.9%, P=0.01). Among women with G1 colposcopy, the rate of CIN3+ lesions was significantly higher in women with fine punctation (P=0.02) while no differences in women with thin acetowhite epithelium or fine mosaic emerged. CONCLUSIONS: In women with CIN2 biopsy, when a G2 pattern or G1 with fine punctation on colposcopy is detected, there is an increased risk of CIN3+ on final histology, therefore an excisional treatment should be preferred. Otherwise, in women with CIN2 biopsy and other G1 patterns on colposcopy, a "wait-and-see" approach could be considered.

An online survey on emotions, impact on everyday life, and educational needs of women with HPV positivity or abnormal Pap smear result.

ABSTRACT: This study aimed to evaluate the emotional path, impact on everyday life, and adequacy of patient education throughout the diagnostic and therapeutic journey of women who received a positive human papillomavirus (HPV) test or Pap smear result.An online survey was designed to determine the demographic characteristics, dominant feelings throughout the diagnostic and therapeutic procedures, major lifestyle changes, impact on social life, and perceived adequacy of patient information in Italian women with a positive HPV test or abnormal cervical cytology result. In this study, the phases of the "patient's journey" included the initial test, waiting for colposcopy or biopsy, waiting for surgery, and follow-up.Anxiety, worry, and fear were the most frequently cited emotions during the initial tests and intervals between procedures. Anxiety and fear gradually decreased during the journey until surgery, and higher levels of optimism were observed postsurgery. The most frequently reported lifestyle changes were attempts to boost the immune system, increased precautions in sexual practices, and dietary changes. Social life is affected by changes in sexual and intimate relationships with partners. Women reported receiving insufficient patient education on the diagnosis and its implications, progression, management, personal care, and resolution.Significant attention should be given to the psychosocial aspects of the entire patient journey after receiving a positive HPV test or an abnormal Pap smear result. It is essential to establish a good rapport between patients and healthcare professionals, and to educate women regarding the condition by minimizing the gap between the perceived and desired adequacy of information.

High-risk HPV positivity is a long-term risk factor for recurrence after cervical excision procedure in women living with HIV.

OBJECTIVE: To evaluate the risk factors for recurrence of high-grade disease after cervical excision in women living with HIV (WLWH), with a specific interest in the role of high-risk (HR-) HPV positivity. METHODS: Multicentric retrospective study conducted on WLWH who underwent cervical excision between January 1987 and June 2017 in six Italian institutions. The rate of high-grade recurrence was determined. Risk factors for recurrence and HR-HPV positivity were determined with the Log-rank test and Cox proportional hazards regression models. RESULTS: A total of 271 WLWH were included in the final analysis. A high-grade recurrence was found in 58 (21.4%) patients. Age 41 years or more at inclusion and HR-HPV positivity during follow up were independently associated with a higher risk of disease recurrence with relative risks of 4.15 (95% confidence interval [CI] 2.01-8.58, P < 0.001) and 5.18 (95% CI 2.12-12.67, P < 0.01), respectively. Age 41 years or more (relative risk 1.75, 95% CI 1.01-3.04, P = 0.047) resulted as a risk factor for HR-HPV positivity during follow up. CONCLUSION: HR-HPV positivity is a risk factor for recurrence after cervical excision in WLWH. Women older than 41 years may benefit from a long-term yearly follow up. Future studies regarding HPV vaccination after treatment in WLWH may be useful, considering the protective role of the higher probability of HPV negativity in vaccinated women.

Battlefield Acupuncture for Adult Pain: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Pain is a major public health problem, causing heavy social and economic burdens to patients and society while consuming tremendous medical resources at the same time. Thus, there is a critical need to find low-cost, efficacious, and therapeutic approaches to help manage pain. While acupuncture is increasingly recognized as a promising pain-relieving method, less is known about a specific form of auricular acupuncture known as Battlefield Acupuncture (BFA). The BFA technique involves the sequential placement of semi-permanent, single-use, French ASP[Formula: see text] golden needles to five specific acupoints in one or both ears, where they are left in place for 3-4 days or longer [Niemtzow, R.C., Battlefield acupuncture. Med. Acupunct. 19: 225-228, 2007]. The BFA needles (more accurately described as tiny conical darts) pierce the ear in designated locations in a particular order [Levy, C.E., N. Casler and D.B. FitzGerald. Battlefield acupuncture: an emerging method for easing pain. Am. J. Phys. Med. Rehabil. 97: e18-e19, 2018.]. (Figs. 4 and 5) It was developed by Dr. Richard C. Niemtzow in 2001, as a subgroup form of an auricular acupuncture technique based on the somatotopic arrangement of an inverted fetus pattern on the external ear [Romoli, M. Ear acupuncture: historical abstract-differences of ear cartography between the east and the west. Dtsch. Z. Akupunkt. 53: 24-33, 2010.]. Currently, BFA is widely used in the US military, but to our knowledge, there is no review which comprehensively synthesizes the current publications surrounding pain management. This review aims to investigate the effects and safety of BFA in adults with pain. Electronic databases were searched for randomized controlled trials (RCTs) published in English evaluating efficacy and safety of BFA in adults with pain, from database inception to September 6, 2019. The primary outcome was pain intensity change, and the secondary outcome was safety. Nine RCTs were included in this review, and five trials involving 344 participants were analyzed quantitatively. Compared with no intervention, usual care, sham BFA, and delayed BFA interventions, BFA had no significant improvement in the pain intensity felt by adults suffering from pain. Few adverse effects (AEs) were reported with BFA therapy, but they were mild and transitory. BFA is a safe, rapid, and easily learned acupuncture technique, mainly used in acute pain management, but no significant efficacy was found in adult individuals with pain, compared with the control groups. Given the poor methodological quality of the included studies, high-quality RCTs with rigorous evaluation methods are needed in the future.

Atypical Endometrial Hyperplasia and Unexpected Cancers at Final Histology: A Study on Endometrial Sampling Methods and Risk Factors.

BACKGROUND: Up to 40% of women with atypical endometrial hyperplasia (AEH) can reveal endometrial cancer (EC) at hysterectomy. The pre-operative endometrial sampling method (ESM) and some independent cancer predictors may affect this outcome. The present study aimed to compare the rate of EC at hysterectomy in women with AEH undergoing dilation and curettage (D&C), hysteroscopically-guided biopsy (HSC-bio), or hysteroscopic endometrial resection (HSC-res). The secondary outcome was to compare the reliability of ESMs in women showing independent variables associated with EC. METHODS: Two-hundred-and-eight consecutive women with AEH and undergoing hysterectomy between January 2000 and December 2017 were analyzed retrospectively. Based on pre- and post-test probability analysis for EC, three ESMs were compared: D&C, HSC-bio, and HSC-res. Univariate and multivariate analyses were performed to assess risk factors predicting cancer on final histology. Finally, the patient's characteristics were compared between the three ESM groups. RESULTS: D&C and HSC-bio included 75 women in each group, while HSC-res included 58 women. Forty-nine women (23.6%) revealed cancer at hysterectomy (pre-test probability). Post-test probability analysis showed that HSC-res had the lowest percentage of EC underestimation: HSC-res = 11.6%; HSC-bio = 19.5%; D&C = 35.3%. Patient characteristics showed no significant differences between the three ESMs. Multivariate analysis showed that body mass index ≥40 (Odds Ratio (OR) = 19.75; Confidence Intervals (CI) 2.193-177.829), and age (criterion > 60 years) (OR = 1.055, CI 1.002-1.111) associated significantly with EC. In women with one or both risk factors, post-test probability analysis showed that HSC-res was the only method with a lower EC rate at hysterectomy compared to a pre-test probability of 44.2%: HSC-res = 19.96%; HSC-bio = 53.81%; D&C = 63.12%. CONCLUSIONS: HSC-res provided the lowest rate of EC underestimation in AEH, also in women showing EC predictors. These data may be considered for better diagnostic and therapeutic planning of AEH.

CELLTOP Clinical Trial: First Report From a Phase 1 Trial of Autologous Adipose Tissue-Derived Mesenchymal Stem Cells in the Treatment of Paralysis Due to Traumatic Spinal Cord Injury.

Spinal cord injury (SCI) is a devastating condition with limited pharmacological treatment options to restore function. Regenerative approaches have recently attracted interest as an adjuvant to current standard of care. Adipose tissue-derived (AD) mesenchymal stem cells (MSCs) represent a readily accessible cell source with high proliferative capacity. The CELLTOP study, an ongoing multidisciplinary phase 1 clinical trial conducted at Mayo Clinic (ClinicalTrials.gov Identifier: NCT03308565), is investigating the safety and efficacy of intrathecal autologous AD-MSCs in patients with blunt, traumatic SCI. In this initial report, we describe the outcome of the first treated patient, a 53-year-old survivor of a surfing accident who sustained a high cervical American Spinal Injury Association Impairment Scale grade A SCI with subsequent neurologic improvement that plateaued within 6 months following injury. Although he improved to an American Spinal Injury Association grade C impairement classification, the individual continued to be wheelchair bound and severely debilitated. After study enrollment, an adipose tissue biopsy was performed and MSCs were isolated, expanded, and cryopreserved. Per protocol, the patient received an intrathecal injection of 100 million autologous AD-MSCs infused after a standard lumbar puncture at the L3-4 level 11 months after the injury. The patient tolerated the procedure well and did not experience any severe adverse events. Clinical signs of efficacy were observed at 3, 6, 12, and 18 months following the injection in both motor and sensory scores based on International Standards for Neurological Classification of Spinal Cord Injury. Thus, in this treated individual with SCI, intrathecal administration of AD-MSCs was feasible and safe and suggested meaningful signs of improved, rather than stabilized, neurologic status warranting further clinical evaluation.

Role of Close Endocervical Margin in Treatment Failure After Cervical Excision for Cervical Intraepithelial Neoplasia: A Retrospective Study.

CONTEXT.­: A significant negative trend in length of cone excision has been observed in recent years, leading to a higher percentage of positive endocervical excision margin and close (<1 mm) negative endocervical margin cases. OBJECTIVE.­: To evaluate the rate of disease persistence and recurrence after cervical excision for cervical intraepithelial neoplasia in relation to a close (<1 mm), negative, or positive endocervical margin. DESIGN.­: We retrospectively analyzed a cohort of patients with cervical intraepithelial neoplasia having a carbon dioxide laser cervical excision performed by the same operator. We evaluated the rate of positive follow-up in relation to the status of endocervical margin. RESULTS.­: We found a higher percentage of positivity at follow-up and recurrence rate between 13 and 24 months in patients with positive margin than for patients with negative or close endocervical margin (P = .005 and P = .006, respectively), with no difference between negative and close margin (7.0% versus 8.3%, P = .89, and 1.2% versus 0%, P = .83, respectively). CONCLUSIONS.­: Women with close and negative endocervical margin presented similar risk of positivity at long-term follow-up, disease persistence, and recurrence between 13 and 24 months, so the histopathologic report of a free endocervical margin less than 1 mm should not categorize the patient as being at increased risk of treatment failure. Therefore, the only information that the pathologist should report is the state of the margin (positive or negative), regardless of the negative endocervical margin length.

An investigation of the relationship between autonomic dysreflexia and intrathecal baclofen in patients with spinal cord injury.

OBJECTIVE: To study the relationship between autonomic dysreflexia and intrathecal baclofen in patients with spinal cord injury. DESIGN: Retrospective chart review. SETTING: Inpatient and outpatient acute rehabilitation facility. PARTICIPANTS: Thirty-four subjects. INTERVENTIONS: We reviewed patients' medical records to ascertain the presence of symptomatic autonomic dysreflexia (AD) prior to and after implantation of an intrathecal baclofen (ITB) pump for spasticity in spinal cord injury patients. We recorded risk factors for autonomic dysreflexia including kidney and bladder stones, heterotopic ossification (HO), and ischial / sacral pressure ulcers. OUTCOME MEASURES: Presence of autonomic dysreflexia pre and post-intrathecal baclofen pump placement, presence of risk factors associated with autonomic dysreflexia including (1) kidney or bladder stones, (2) heterotopic ossification, and (3) pressure ulcers. RESULTS: Of the 34 subjects, 25 (73.5%) experienced AD prior to ITB pump placement and only 2 (5.9%) after placement. Four subjects (11.8%) had kidney or bladder stones, of which, all had AD prior to placement and none had AD afterwards. Twenty-six subjects (76.5%) had pressure ulcers, of which, all experienced AD prior to placement and only one (0.02%) afterwards. Six patients (17.6%) had HO, of which 5 (83%) had AD prior to placement and none afterwards. Additionally, three patients (8.8%) had at least 2 of the above risk factors, of which, all had AD prior to ITB placement and none afterwards. CONCLUSION: This study showed a significant reduction of symptomatic episodes of autonomic dysreflexia after spinal cord injury, even in those with additional risk factors for development of autonomic dysreflexia.