Gynaecological cylindroma in association with CYLD gene mutation.

Cylindroma is a benign adnexal tumour that occurs as a solitary pink-red coloured nodule and is usually found on the scalp or neck. There have been few cases reported of these lesions being found on the genitalia. They can be found in single or in multiple form, with the latter usually inherited in an autosomal dominant pattern. CYLD lysine 63 deubiquitinase (CYLD) cutaneous syndrome, also known as Brooke-Spiegler syndrome, is a genetic condition characterized by the growth of multiple benign adnexal skin tumours. The most common tumours are cylindromas, spiradenomas and trichoepitheliomas. The cause of this syndrome can be attributed to mutations in the CYLD tumour suppressor gene. If both copies of this gene are mutated, the cell undergoes uncontrolled cell proliferation and division resulting in the formation of a tumour. Here, we present an unusual case of a female patient presenting with a large cylindroma over the mons pubis.

Stage one endometrioid endometrial adenocarcinoma: is there a role of traditional hospital follow-up in the detection of cancer recurrence in women after treatment?

OBJECTIVE: To investigate the rate of asymptomatic recurrence of stage 1 endometrioid endometrial cancer and assess the role of routine hospital follow-up after treatment. METHODS: We performed a retrospective case-note review study of women who were diagnosed with stage 1 endometrioid endometrial adenocarcinoma at Queen's Hospital, Romford, between January 2008 and December 2016. RESULTS: We included 299 patients with a median follow-up period of 44.4 months. All the patients underwent total hysterectomy and bilateral salpingo-oophorectomy. Adjuvant radiotherapy was offered to the patients subsequent to discussions in the multidisciplinary team meeting in accordance with the risk stratification criteria. There was no significant correlation between the risk factors and disease recurrence. In total, 11 patients presented with recurrent disease with original staging: 1a, n=6/199; and 1b, n=5/100. Four patients presented with vaginal bleeding due to vault recurrence and one patient with abdominal pain due to pelvic mass. Locoregional recurrence was an incidental finding in two other patients. Four patients presented with symptomatic distant metastases to the lung (n=2), liver (n=1), and bone (n=1). No asymptomatic recurrences were identified on routine follow-ups, despite several hospital appointments and clinical examinations. The recurrence rate for patients with stage 1a and 1b, grade 1, and grade 2 disease was 3.53%, and that for patients with stage 1a, grade 1, and grade 2 disease was 2.7%. CONCLUSION: Routine clinical examinations have a low yield in finding recurrence in asymptomatic women and should be questioned for their value, considering the limited resources of the National Health Service (NHS). Larger studies are required to support a stratified follow-up, which will include telephone and patient-initiated follow-up.

Cervical glandular neoplasia referrals and the diagnosis of adenocarcinoma in situ: Correlating cytology, colposcopy findings, and clinical outcomes.

OBJECTIVES: To determine the clinical outcomes of women with possible glandular neoplasia of endocervical type on cervical cytology, and review all diagnoses of cervical adenocarcinoma in situ (AIS) over a 5 year period at our institution. STUDY DESIGN: A retrospective case-note review was conducted of all women referred to colposcopy with possible glandular neoplasia of endocervical type on cervical cytology or diagnosed with cervical AIS after biopsy or excision, from January 2014 until December 2018 in a London district hospital. RESULTS: Of 55 women referred with possible glandular neoplasia of endocervical type, 47 (85.4%) had a significant pathology on histopathological analysis: AIS (n = 22); invasive cancer (n = 7); high-grade cervical intraepithelial neoplasia (n = 18). Women with a history of borderline abnormality on cervical cytology within the last 5 years were significantly more likely to be diagnosed with AIS or invasive cancer (P < .05). For the same period 49 women had histologically proven AIS. Among these 22 (44.8%) were referred as possible cervical glandular intraepithelial neoplasia. Other reasons for referral were the following indications: borderline dyskaryosis (n = 13); high-grade dyskaryosis (n = 8); low-grade dyskaryosis (n = 4); postcoital bleeding (n = 2). CONCLUSION: Due to the raised risk of significant gynaecological pathology in women with possible glandular neoplasia of endocervical type on cervical cytology, excisional biopsy is essential. Colposcopic impression varies significantly and complete excision of the abnormal lesions should be achieved. AIS is a histological diagnosis and should always be considered during colposcopical and cytopathological assessment.

Multizonal anogenital neoplasia in women: a cohort analysis.

BACKGROUND: There is currently a lack of information on full anogenital evaluation of women with a previous history of anogenital neoplasia. METHODS: Retrospective analysis of the Homerton Anogenital Neoplasia Service records from January 2012 to March 2017, to identify all new referrals of women with previous anogenital neoplasia, who had had at least one complete examination of all anogenital sites. Multizonal anogenital disease (MZD) was defined as the presence of high-grade squamous intraepithelial lesions (HSIL)/carcinoma concurrently at two or more of the following sites/zones: perianus, anal canal, vulva, vagina or cervix. RESULTS: 253 women were included, mean age was 47 (SD=15) years and median duration of follow-up was 12 (IQR=21) months. Fifty-six women (22%) were diagnosed with MZD at first assessment and/or during follow-up. Current smokers (RR=1.84, 95% CI 1.21-2.79, p=0.004) and women on immunodulators/immunosuppressive drugs (RR=2.57, 95% CI 1.72-3.86, p<0.001) had an increased risk for MZD. The risk was lower for women without a previous history of anogenital high-grade lesions/cancer compared to those with this history (RR=0.06, 95% CI 0.01-0.45, p=0.006). CONCLUSIONS: Multizonal assessment was important to diagnose occult areas of disease and should be especially considered in current smokers, pharmacologically immunocompromised and those with a previous history of anogenital HSIL/cancer.

Presentation of an open entry technique for laparoscopy through a congenital defect in the umbilical fascia.

OBJECTIVE: We present and describe a modification of the Hasson open entry technique to gain access to the abdominal cavity for laparoscopy in which a congenital defect in the umbilical fascia is identified for entry into the peritoneum and insertion of the primary port. METHODS: A single centre, prospective, observational, pilot study has been conducted with no change in clinical practice. Data regarding the success of the technique, time to laparoscope insertion, complications and patient risk factors were collected and presented. RESULTS: The team enrolled 114 patients that had the St Helier technique attempted for entry in the abdominal cavity. Entry was achieved for all patients. The technique had 82.5 % success rate while this reduced to 65 % in patients with previous laparoscopies. The mean time to insertion of the laparoscope was 220 s, and there was no significant difference in success with variation in BMI. We recorded no minor or significant intra-operative complications. The superficial wound infection rate was 2.6 % with no other postoperative complications identified at 6-week follow-up. CONCLUSIONS: The presented technique is a safe and successful method of laparoscopic entry with a presumed shorter time until laparoscope insertion than other techniques used. The absence of complications could be attributed to the avoidance of sharp dissection of the umbilical fascia. The less invasive nature could reduce risks of hematoma, infection or hernia that are associated with the standard entry techniques used. Formal studies of long-term outcomes are required, as well as evaluating use in emergency and contaminated cases.

Medically unfit women with early-stage endometrial cancer treated with the levonorgestrel intrauterine system.

OBJECTIVE: To assess the clinical efficacy of the levonorgestrel intrauterine system (LNG-IUS) in the treatment of early-stage endometrial cancer in elderly morbidly obese women, whose multiple co-morbidities made the standard surgical treatment too risky to undertake. METHODS: A retrospective review was conducted and case series reports were prepared of all women diagnosed with endometrial cancer, from April 2011 to December 2016 at the Queen's Hospital, London, to identify women unfit for surgery and treated with the LNG-IUS. RESULTS: Out of 438 women with endometrial cancer, Eight women with early-stage endometrial cancer were deemed unfit for surgery and underwent treatment with the LNG-IUS. All had grade 1 endometrioid endometrial adenocarcinoma, radiologically staged as 1a. Four women died of their co-morbidities, not related to endometrial cancer. One of them had 68 months of progression-free survival before death due to co-morbidities. One patient required a hysterectomy after 32 months of treatment with LNG-IUS and oral progestogens due to heavy vaginal bleeding. Three women have continued the LNG-IUS treatment with no evidence of progressive disease symptoms till date at a mean follow-up of 35.7 months. CONCLUSION: For women with multiple co-morbidities, the LNG-IUS offers an effective and safe treatment for early-stage, low-grade endometrial cancer, with no cases of symptomatic progression reported in our case series. In the frail and elderly, where the quality of life is of paramount importance, surgical treatment may not offer additional long-term survival benefits.

Rural Zulu women's knowledge of and attitudes towards Pap smears and adherence to cervical screening.

BACKGROUND: Cervical cancer is the most common form of cancer in black women in South Africa and has almost a 60% mortality rate. However, adherence to cervical screening programmes of black women living in rural South Africa is not universal. AIM: The aim of this study was to gain a better understanding of rural Zulu women's knowledge of and attitudes towards Pap smear tests, and their reasons for participation or non-compliance with cervical screening. SETTING: This study was conducted at the gynaecology and antenatal clinics in a secondary referral hospital in rural KwaZulu-Natal. METHODS: A hospital-based cross-sectional study was undertaken in the form of a semi-structured patient questionnaire survey with open and closed questions. The responses to the open-ended questions were manually analysed by the authors using a thematic approach. Outcome measures included whether the woman had a previous Pap smear, her understanding of the cervical screening programme and causes of cervical cancer. RESULTS: This study included a total analysis of 234 responses. The mean age was 29 years (s.d. = 8.3 years). Overall, 32.5% of women had previously had a Pap smear. Among the responders, 33.3% were human immunodeficiency virus (HIV)-positive and 53.0% were HIV-negative. Only 19.2% of women understood that a Pap smear was related to screening for cervical cancer. CONCLUSIONS: This study illustrated a poor understanding of cervical screening, which may result in the low level of uptake of Pap smear reported; this is particularly concerning in HIV-positive women, who are at higher risk of developing cervical cancer. Urgent and extensive public health campaigning is required within rural South Africa to improve cervical screening uptake and decrease cervical cancer mortality.

Post-coital bleeding: What is the incidence of significant gynaecological pathology in women referred for colposcopy?

OBJECTIVE: To evaluate the incidence of underlying serious gynaecological pathology in women referred to colposcopy with post-coital bleeding. MAIN OUTCOME MEASURES: Incidence of precancer and cancer. METHODS: A retrospective cohort study of women referred to colposcopy at a London hospital from January 2008-March 2015. Inclusion criteria are women with post-coital bleeding and the following cervical cytology history: negative; inadequate; never had. Multinomial logistic regression was used to assess for significant risk factors for cervical dysplasia and cancer. RESULTS: Overall, 635 women with either negative cytology (n = 436/68.7%), no previous cytology (n = 175/27.6%), or inadequate cytology (n = 24/3.8%) were referred to colposcopy for post-coital bleeding. The median age is 35 years (S.D. = 9.7 years). In 256 (40.3%) women, no cause was detected, and 322 (50.7%) women had a benign cause. Overall, 42 (6.6%) women had low-grade dysplasia, and eleven women had high-grade dysplasia (1.7%). Four women (0.6%) had cervical cancer; clinically evident cancer on speculum examination (n = 3); micro-invasive cancer (n = 1). Current smokers were significantly more likely to have HPV atypia (p = 0.015) or cervical intraepithelial neoplasm grade 1 (CIN1) p = 0.003. Advancing age was a significant risk factor for cervical cancer (p = 0.037). CONCLUSION: All women with post-coital bleeding need an urgent speculum examination to rule out frank cervical cancer. Although most women had a benign cause for post-coital bleeding, around 2% had a colposcopy-aided diagnosis of either cervical precancer or cancer; therefore, referral of symptomatic women deserves consideration. HPV testing may reduce referrals to colposcopy for post-coital bleeding due to non-significant pathology in the future.

Conservative management of cervical intraepithelial neoplasia grade 2 (CIN2) in women under 30 years of age: A cohort study.

OBJECTIVE: To assess the safety of conservative management of cervical intraepithelial neoplasia grade 2 (CIN2) in women aged under 30 years. STUDY DESIGN: A retrospective cohort study at Queen's Hospital, London, UK. We reviewed patient records and 'Open Exeter' cytology results of 178 women aged less than 30 years with histologically proven CIN2 between 1st April 2014 and 31st March 2016. Analysis included rates of spontaneous regression of CIN2, the persistence of abnormality, the progression to CIN3 and cancer, duration of conservative management, and the number of patients that defaulted follow-up. RESULTS: Of 178 women, 69 women underwent primary treatment of CIN2 with large loop excision of the transformation zone (LLETZ). Nine women defaulted follow-up after their first appointment. One hundred women were managed conservatively with colposcopy, cytology and cervical biopsy. Overall 57% had successful conservative management with regression of high-grade lesion on colposcopy and negative cytology; 32% had failed conservative management and LLETZ, and 11% of women defaulted follow-up with abnormal cytology. Only 13% of women managed conservatively progressed to CIN3, with no woman developing cancer at a median follow-up of 22 months. In women with successful conservative management features of high-grade dysplasia on colposcopy resolved in a significantly shorter time-period compared to normalisation of their cytology (p = 0.021). CONCLUSION: Conservative management of CIN2 appears reasonable and safe in women under the age of 30 years, with 57% showing regression to negative cytology. There is a significant time lag before cytology becomes negative, so early recourse to treatment based on cytology alone is not advised where colposcopy is satisfactory and reassuring.

A comparison of non-integrating reprogramming methods.

Human induced pluripotent stem cells (hiPSCs) are useful in disease modeling and drug discovery, and they promise to provide a new generation of cell-based therapeutics. To date there has been no systematic evaluation of the most widely used techniques for generating integration-free hiPSCs. Here we compare Sendai-viral (SeV), episomal (Epi) and mRNA transfection mRNA methods using a number of criteria. All methods generated high-quality hiPSCs, but significant differences existed in aneuploidy rates, reprogramming efficiency, reliability and workload. We discuss the advantages and shortcomings of each approach, and present and review the results of a survey of a large number of human reprogramming laboratories on their independent experiences and preferences. Our analysis provides a valuable resource to inform the use of specific reprogramming methods for different laboratories and different applications, including clinical translation.

Emergency department boarding times for patients admitted to intensive care unit: Patient and organizational influences.

INTRODUCTION: Critically ill patients can be subject to prolonged stays in the emergency department following receipt of an order to admit to an intensive care unit. The purpose of this study was to explore patient and organizational influences on the duration of boarding times for intensive care bound patients. METHODS: This exploratory descriptive study was situated in a Canadian hospital in northern Ontario. Through a six-month retrospective review of three data sources, information was collected pertaining to 16 patient and organizational variables detailing the emergency department boarding time of adults awaiting transfer to the intensive care unit. Data analysis involved descriptive and non-parametric methods. RESULTS: The majority of the 122 critically ill patients boarded in the ED were male, 55 years of age or older, arriving by ground ambulance on a weekday, and had an admitting diagnosis of trauma. The median boarding time was 34 min, with a range of 0-1549 min. Patients designated as most acute, intubated, and undergoing multiple diagnostic procedures had statistically significantly shorter boarding times. DISCUSSION: The study results provide a profile that may assist clinicians in understanding the complex and site-specific interplay of variables contributing to boarding of critically ill patients.

Arterial blood gas results rarely influence emergency physician management of patients with suspected diabetic ketoacidosis.

OBJECTIVES: To test the hypothesis that arterial blood gas (ABG) results for patients with suspected diabetic ketoacidosis (DKA) do not influence emergency physicians' management decisions and to assess correlation and precision between venous pH and arterial pH. METHODS: Prospective, observational study of emergency physicians' decision making for consecutive ED patients with suspected DKA. Inclusion criteria were capillary blood glucose equal to or greater than 200 mg/dL, ketonuria, and clinical signs and symptoms of DKA. Venous pH, chemistry panel, and ABGs were drawn before treatment. Attending emergency physicians indicated planned management and disposition on a standardized form before and after reviewing ABG and venous pH results. This study was powered to detect a 10% difference in management decisions (n = 195). Pearson's correlation and Bland-Altman bias plot were used to compare venous pH and arterial pH. RESULTS: ABG analysis changed the emergency physicians' diagnosis in 2/200 cases (1.0%; 95% confidence interval [95% CI] = 0.3% to 3.6%), altered treatment in 7/200 cases (3.5%; 95% CI = 1.7% to 7.1%), and changed disposition in 2/200 cases (1.0%; 95% CI = 0.3% to 3.6%). The pH value of the ABGs changed the treatment or disposition in 5/200 patients (2.5%; 95% CI = 1.1% to 5.7%). The Po(2) and Pco(2) results of the ABGs altered treatment and disposition in 2/200 patients (1.0%; 95% CI = 0.3% to 3.6%). Venous pH correlated well with arterial pH (r = 0.951), and bias plotting yielded a bias value of -0.015 (+/- 0.006 pH units). CONCLUSIONS: ABG results rarely influenced emergency physicians' decisions on diagnosis, treatment, or disposition in suspected DKA patients. Venous pH correlated well and was precise enough with arterial pH to serve as a substitute.