New paradigms for BRCA1/BRCA2 testing in women with ovarian cancer: results of the Genetic Testing in Epithelial Ovarian Cancer (GTEOC) study.

BACKGROUND: Over recent years genetic testing for germline mutations in BRCA1/BRCA2 has become more readily available because of technological advances and reducing costs. OBJECTIVE: To explore the feasibility and acceptability of offering genetic testing to all women recently diagnosed with epithelial ovarian cancer (EOC). METHODS: Between 1 July 2013 and 30 June 2015 women newly diagnosed with EOC were recruited through six sites in East Anglia, UK into the Genetic Testing in Epithelial Ovarian Cancer (GTEOC) study. Eligibility was irrespective of patient age and family history of cancer. The psychosocial arm of the study used self-report, psychometrically validated questionnaires (Depression Anxiety and Stress Scale (DASS-21); Impact of Event Scale (IES)) and cost analysis was performed. RESULTS: 232 women were recruited and 18 mutations were detected (12 in BRCA1, 6 in BRCA2), giving a mutation yield of 8%, which increased to 12% in unselected women aged <70 years (17/146) but was only 1% in unselected women aged ≥70 years (1/86). IES and DASS-21 scores in response to genetic testing were significantly lower than equivalent scores in response to cancer diagnosis (p<0.001). Correlation tests indicated that although older age is a protective factor against any traumatic impacts of genetic testing, no significant correlation exists between age and distress outcomes. CONCLUSIONS: The mutation yield in unselected women diagnosed with EOC from a heterogeneous population with no founder mutations was 8% in all ages and 12% in women under 70. Unselected genetic testing in women with EOC was acceptable to patients and is potentially less resource-intensive than current standard practice.

The use of laparostomy in patients with gynecologic cancer: first report from a UK cancer center.

OBJECTIVE: To report on the use of laparostomy after major gynecologic cancer surgery. METHODS: Operative records and surgical databases of patients who underwent major open abdominal surgery over a 6.5-year period at a tertiary referral center were searched. Patients who had diagnostic procedures, operative laparoscopy, and surgery for vulval cancer were excluded. All patients who had laparostomy were identified; and the diagnosis, indication for laparostomy, method of temporary cover, and complications were recorded. RESULTS: A total of 1592 laparotomies, including 37 emergencies, were performed. Of these, 14 patients (0.88%) had a laparostomy. Seven patients had primary cancer and 7 had recurrent cancer. As more patients had surgery for primary disease, laparostomy was more common in patients who underwent surgery for recurrent cancer. Seven patients had ovarian/fallopian tube/primary peritoneal cancer, 4 patients had uterine cancer, 2 patients had cervical cancer, and one patient had vaginal cancer. Ten laparostomies (71.4%) were performed after an emergency procedure; thus, laparostomy was approximately 100 times more common after emergency than elective major surgery. Massive bowel distension and bowel wall edema were the major indications for laparostomy. The method of temporary closure was variable, and a sterile saline bag was the most commonly used. The laparostomy was closed in all but 2 patients, most often on postoperative day 2 or 3. Two patients (14.3%) died within 30 days of the laparostomy, and 2 others died at postoperative days 40 and 62. Three of these 4 patients had recurrent cancer, and 2 patients had emergency procedures. CONCLUSIONS: The overall incidence of laparostomy associated with laparotomy for gynecological cancer surgery was less than 1:100 cases, was more common after surgery for recurrent cancer, and in particular, was approximately 100 times more common after emergency procedures. The 30-day operative mortality rate was 14.3%.

Diagnostic performance of urgent referrals for suspected gynaecological malignancies.

PURPOSE: The objective of this study was to investigate the outcome of the urgent referrals with suspected gynaecological malignancy. METHODS: Retrospective analysis of the data of the urgent referrals for suspected gynaecological cancers over a 12-month period at a gynaecological oncology cancer centre in the UK. RESULTS: A total of 233 patients (70.61%) were referred with suspected endometrial pathology, 59 patients (17.88%) with suspected ovarian, 25 patients (7.58%) with suspected cervical and 13 patients (3.94%) with suspected vulval malignancy. The positive predictive value of referrals for diagnosing endometrial, ovarian, cervical and vulval malignancy was 11.6, 23.7, 12.0 and 15.4%, respectively. Amongst the indications for referral for suspected endometrial cancer, presence of postmenopausal vaginal bleeding had the higher odds for cancer (odds = 0.13; 95% CI 0.08-0.21). The odds for cancer for women referred with a pelvic mass was 0.17 (95% CI, 0.07-0.42) and for women referred with abdominal bloating was 0.66 (95% CI, 0.18-2.36). All the cases of malignancy were diagnosed in women referred with suspicious appearance of the cervix on clinical examination. The odds for cancer was 0.50 if the indication for referral was vulval itching. The majority of cases of gynaecological cancers during the study period were diagnosed following routine referrals. CONCLUSION: The overall predictive value of two-week wait referrals for suspected gynaecological malignancies is low. Refinement of the current referral guidelines is required with particular emphasis in the premenopausal women where the diagnostic performance of the urgent referrals is significantly poorer.

Risk factors and sonographic endometrial thickness as predictors of tumour stage and histological subtype of endometrial cancer.

We evaluated the association between risk factors for endometrial cancer (EC) and sonographic endometrial thickness (ET) with FIGO stages at diagnosis. We also reported our experience in reliability of sonographic ET as screening tool for either histologic subtype I and II of EC. It was a case series study including 339 patients diagnosed with EC from 2010 to 2017 at the Ipswich Hospital, UK. Women with higher body mass index (BMI) presented at earlier stages when compared to women with lower BMIs (p-value = .046). By contrast, none of the variables: parity (p-value = .1630), use of HRT (p-value 0.7448), tamoxifen (p-value 0.0733) and diabetes (p-value = .1665) were statistically associated to FIGO stages. The mean of ET measurement was not statistically significant associated (p-value 0.0625) to stages. There was no statistic difference on mean ET at diagnosis between histologic subtypes I or II (p-value 0.804). According to our experience, BMI is associated to FIGO stage and endometrial sampling (ES) should be included in the working diagnosis of EC to obtain an early diagnosis in women with high BMIs even in premenopausal. Ultrasonographic measurement of the endometrium is equally reliable at determining cancer, but not at differentiating histologic subtypes I and II uterine cancers. However, ET does not correlate to FIGO stages at diagnosis.

Risk factors for HPV persistence and cytology anomalies at follow-up after treatment for cervical dysplasia.

OBJECTIVE: To evaluate predictor factors of persistent cytologic dysplasia and/or high-risk human papillomavirus (hrHPV) infection at 6-month follow-up and at 3-5 years during routine cervical smear testing. METHODS: The present retrospective study included data from women treated for cervical dysplasia by large loop excision of the transformation zone (LLETZ) at Ipswich Hospital, UK, between January 1 and December 31, 2012. Age, parity, smoking, status of resection margins, and previous LLETZ treatment were evaluated by multivariate analyses. RESULTS: There were 192 patients included in the study. There was no association between age (relative risk [RR] 1.0, 95% confidence interval [CI] 0.80-1.23; P>0.99), smoking (RR 1.12, 95% CI 0.79-1.59; P=0.516), or parity (RR 1.10, 95% CI 0.88-1.38; P=0.382) and abnormal cytology and/or persistent hrHPV infection at 6 months. There was an association between positive margins (RR 1.64, 95% CI 1.20-2.24; P=0.003), previous LLETZ (RR 3.48, 95% CI 1.69-7.15; P<0.001), and dyskaryosis and/or hrHPV infection at 6 months. Only previous LLETZ treatment remained associated with abnormal cytology and persistent hrHPV infection at 3-5 years (RR 6.37, 95% CI 3.56-11.3; P<0.001). CONCLUSION: Clinical factors, including age, smoking, treatment history, and status of surgical margins, could help to determine the risk of dysplasia recurrence and facilitate patient follow-up based on risk stratification.

Prospective study using the risk of ovarian cancer algorithm to screen for ovarian cancer.

PURPOSE: To evaluate prevalence screening in the first prospective trial of a new ovarian cancer screening (OCS) strategy (risk of ovarian cancer or ROC algorithm) on the basis of age and CA125 profile. PATIENTS AND METHODS: Postmenopausal women, > or = 50 years were randomly assigned to a control group or screen group. Screening involved serum CA125, interpreted using the ROC algorithm. Participants with normal results returned to annual screening; those with intermediate results had repeat CA125 testing; and those with elevated values underwent transvaginal ultrasound (TVS). Women with abnormal or persistently equivocal TVS were referred for a gynecologic opinion. RESULTS: Thirteen thousand five hundred eighty-two women were recruited. Of 6,682 women randomly assigned to screening, 6,532 women underwent the first screen. After the initial CA125, 5,213 women were classified as normal risk, 91 women elevated, and 1,228 women intermediate. On repeat CA125 testing of the latter, a further 53 women were classified as elevated risk. All 144 women with elevated risk had TVS. Sixteen women underwent surgery. Eleven women had benign pathology; one woman had ovarian recurrence of breast cancer; one woman had borderline; and three women had primary invasive epithelial ovarian cancer (EOC). The specificity and positive predictive value (PPV) for primary invasive EOC were 99.8% (95% CI, 99.7 to 99.9) and 19% (95% CI, 4.1 to 45.6), respectively. CONCLUSION: An OCS strategy using the ROC algorithm is feasible and can achieve high specificity and PPV in postmenopausal women. It is being used in the United Kingdom Collaborative Trial of Ovarian Cancer Screening and in the United States in both the Cancer Genetics Network and the Gynecology Oncology Group trials of high-risk women.

Malignant clear cell hidradenoma of the vulva: report of a unique case and review of the literature.

Clear cell hidradenoma (CCH) is a rare tumor derived from eccrine sweat glands with a predilection for the head, face, and upper extremities. Its biologic behavior is unpredictable, although frank malignant transformation is reportedly rare (prevalence rate, 6.7% in a review). Malignant CCH (MCCH) exists only as case reports or very small series in the literature. We present a unique case of MCCH of the vulva with completely bland cytological features. A previously healthy 39-year-old woman underwent marsupialization of a presumed left-side vulval Bartholin gland cyst. Microscopy revealed a tumor with the features of CCH; no atypia, necrosis, or mitoses were observed. Ten months later, she developed enlarging left groin nodes, one of which contained a metastatic clear cell tumor. Radiological examination did not reveal any other primary source, and the diagnosis of MCCH was confirmed through an expert review. A reexcision of the vulval primary site, which contained residual tumor, was performed. The patient is currently free of any further recurrence 10 months after the excision of the lymph node metastasis. The case highlights the difficulty in predicting the behavior of CCH on the basis of histological examination alone. It also highlights the importance of considering MCCH in the differential diagnosis of a lymph node containing a metastatic clear cell tumor or an apparent metastatic clear cell lesion in the skin. We review the current literature on MCCH and discuss the problems in the differential diagnosis and treatment of this rare tumor.