Correction: Safety and utility of image-guided research biopsies in relapsed high-grade serous ovarian carcinoma-experience of the BriTROC consortium.

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Safety and utility of image-guided research biopsies in relapsed high-grade serous ovarian carcinoma-experience of the BriTROC consortium.

BACKGROUND: Investigating tumour evolution and acquired chemotherapy resistance requires analysis of sequential tumour material. We describe the feasibility of obtaining research biopsies in women with relapsed ovarian high-grade serous carcinoma (HGSC). METHODS: Women with relapsed ovarian HGSC underwent either image-guided biopsy or intra-operative biopsy during secondary debulking, and samples were fixed in methanol-based fixative. Tagged-amplicon sequencing was performed on biopsy DNA. RESULTS: We screened 519 patients in order to enrol 220. Two hundred and two patients underwent successful biopsy, 118 of which were image-guided. There were 22 study-related adverse events (AE) in the image-guided biopsies, all grades 1 and 2; pain was the commonest AE. There were pre-specified significant AE in 3/118 biopsies (2.5%). 87% biopsies were fit-for-purpose for genomic analyses. Median DNA yield was 2.87 µg, and was higher in biopsies utilising 14 G or 16 G needles compared to 18 G. TP53 mutations were identified in 94.4% patients. CONCLUSIONS: Obtaining tumour biopsies for research in relapsed HGSC is safe and feasible. Adverse events are rare. The large majority of biopsies yield sufficient DNA for genomic analyses-we recommend use of larger gauge needles and methanol fixation for such biopsies, as DNA yields are higher but with no increase in AEs.

CT scan does not predict optimal debulking in stage III-IV epithelial ovarian cancer: a multicentre validation study.

Our aim was to design and validate a model of CT findings that predict suboptimal cytoreduction in primary surgery (PS) for Stage III-IV epithelial ovarian cancer (EOC). We performed a retrospective review of preoperative CT scans of patients undergoing PS for EOC in a cancer centre in London, UK, between November 1995 and October 2003 (n = 91). Radiological features predictive of suboptimal cytoreduction were identified and the model tested in a second cohort undergoing PS in Manchester, June 2005 - March 2007 (n = 35). In the London cohort, liver surface disease and infrarenal para-aortic lymph node involvement predicted suboptimal cytoreduction with 80% accuracy. Accuracy of these predictors dropped to 63% when applied to the Manchester cohort. We concluded that CT prediction of suboptimal cytoreduction is unreliable and may not be reproducible. In the absence of favourable data from larger, prospective trials, it should not be used to guide management.

Laparoscopic staging for apparent early stage ovarian or fallopian tube cancer. First case series from a UK cancer centre and systematic literature review.

OBJECTIVE: To describe the experience of laparoscopic staging of apparent early stage adnexal cancers. METHODS: Prospectively collected data on women who had laparoscopic staging for apparent early stage adnexal cancers from May 2008 to September 2012 was reviewed. All women had had a prior surgical procedure at which the diagnosis was made, without comprehensive staging. A systematic MEDLINE search from 1980 to 2012 for publications on laparoscopic staging was performed. RESULTS: Thirty-five women had laparoscopic staging. Median age was 45 years (range 21-73). Median operative time was 210 min (range 90-210). Four intra-operative and one post-operative complication occurred; overall complication rate 5/35 (14%). One vena cava and one transverse colon injury underwent laparotomies for repair. Laparotomy conversion rate 2/35 (6%). Following laparoscopic staging, the cancer was upstaged for eight (23%) women; microscopic omental involvement (four women), pelvic lymph node involvement (two women), para-aortic lymph node involvement (one woman) and contra-lateral ovarian involvement (one woman). After follow up for a median of 18 months (range 3-59) the disease free survival was 94% and overall survival was 100%. Nine studies were identified on laparoscopic staging of adnexal cancer, of which this is the largest single institution series. CONCLUSIONS: This study adds to the evidence that laparoscopic staging is at least as safe as staging by laparotomy with appropriate and similar oncological outcomes, but with the advantages of minimal access surgery. We therefore advocate the use of laparoscopy to achieve surgical staging for women with presumed early stage adnexal cancer.

Ovarian recurrence from a Stage 1b1 cervical adenocarcinoma previously treated with radical vaginal trachelectomy: A case report.

► Post cervical cancer treatment new pelvic abnormality must be regarded as recurrence. ► Benign MRI features does not exclude recurrence from previous cervical adenocarcinoma.

Survey of surgical experience during training in obstetrics and gynaecology in the UK.

The 2002 RCOG survey of training reported that the percentage of obstetric and gynaecology trainees who class their operative training as good or very good has declined from 45% in 1995, to 39% in 2002; reduction in years of training and number of working hours may have further impact on the surgical experience. In this study, we have attempted to assess the level of surgical confidence reported by senior and recently accredited trainees in obstetrics and gynaecology in the UK via an anonymised postal questionnaire. A total of 103 replies were received from 202 questionnaires. Some 99% of the respondents said they felt competent to carry out a simple total abdominal hysterectomy; 61.2% could confidently dissect the ureter and 55.3% could repair major damage to the bladder. However, when managing major obstetric haemorrhage, only 44.6% of respondents felt confident to perform a caesarean hysterectomy; 27.1% could dissect the ureter and 41.7% could apply a B-Lynch suture to the uterus. The level of competence increased with seniority and also with additional time spent in research, subspecialty training or other specialties. There appears to be an appropriate level of confidence in carrying out gynaecological surgical procedures by senior trainees and new consultants. However, surprisingly few respondents were confident in performing any surgical procedure necessary in the management of major obstetric haemorrhage. This may have serious implications in the provision of out of hours senior cover for maternity units in the future.

Integrin beta1 is required for the invasive behaviour but not proliferation of squamous cell carcinoma cells in vivo.

Integrin beta1 is both overexpressed and in an 'active' conformation in vulval squamous cell carcinomas (VSCCs) compared to matched normal skin. To investigate the significance of integrin beta1 deregulation we stably knocked-down integrin beta1 expression in the VSCC cell line A431. In vitro analysis revealed that integrin beta1 is required for cell adhesion, cell spreading and invasion. However, integrin beta1 is not required for cell growth or activation of FAK and ERK signalling in vitro or in vivo. Strikingly, while control tumours were able to invade the dermis, integrin beta1 knockdown tumours were significantly more encapsulated and less invasive.

Preoperative predictors of suboptimal primary surgical cytoreduction in women with clinical evidence of advanced primary epithelial ovarian cancer.

INTRODUCTION: Women with epithelial ovarian cancer (EOC) are conventionally treated with primary cytoreductive surgery. For those with a low probability of optimal primary surgical debulking, an alternative management option is primary chemotherapy with delayed primary surgery. Selection criteria are required to identify women who may benefit from this approach. PATIENTS AND METHODS: Patient age, presence of ascites, preoperative serum CA-125 level, surgical procedures performed, postoperative residual disease, FIGO stage, and histology data were collected on 97 women with preoperative clinical evidence of advanced EOC. Univariate and multivariate analysis was performed to identify which preoperative factors predict disease that will be suboptimally debulked. Receiver-operator curves were constructed for CA-125 level as a predictor for residual disease. RESULTS: The best predictor of disease suboptimally cytoreduced was serum CA-125 level (OR = 22.76, 95% CI = 7.13-72.69). Other predictive factors included age over 60 years (OR = 3.16, 95% CI = 1.04-9.56) and clinical evidence of ascites (OR = 3.30, 95% CI = 1.03-10.62). The optimal cut-off for serum CA-125 as a predictor of suboptimal debulking was 586 IU (sensitivity 80.0%, specificity 88.5%, PPV 85.7%). CONCLUSION: Serum CA-125 level is a reliable component of the preoperative assessment of women with EOC.

The gynaecological management of women on tamoxifen: a national questionnaire survey.

Tamoxifen is the standard adjuvant treatment for women with breast carcinoma, decreasing the incidence of contralateral disease. However, the risk of endometrial cancer is increased. To establish current gynaecological management of women receiving tamoxifen in the United Kingdom we conducted a postal questionnaire of consultant gynaecologists, enquiring about frequency of, and methods used to investigate women on tamoxifen. Ninety-five per cent investigate women on tamoxifen only if they are symptomatic. Pelvic ultrasound and endometrial sampling are used for first-line investigation by 68.7%. Interpreting ultrasound findings, endometrial thickness is the parameter regarded as most important. An endometrial thickness of greater than 5 mm is regarded abnormal by 47.8% of respondents and of 4 mm by 23.6%. As there is no consensus of opinion regarding normal values for endometrial thickness, further data are required to ensure consistency when interpreting ultrasound reports of women on tamoxifen.

Assessment of the cervix in the third trimester of pregnancy using transvaginal ultrasound scanning.

OBJECTIVES: To evaluate the inter- and intra-observer reproducibility of a technique for examining physical characteristics of the uterine cervix in the third trimester of pregnancy using transvaginal ultrasound scanning (TVS). STUDY DESIGN: Forty-six women of over 27-week-gestation underwent TVS of the cervix using a Toshiba 140 scanner with a 6 MHz probe. Twenty were scanned once and 14 women twice by the same operator, and another 12 women by two different operators. Measurements of cervical length, including length and width and opening of the internal os were taken from hardcopy images. Of the 26 women scanned twice, sets of images were analysed by a blinded single observer. Of the 20 women scanned once, measurements from the hardcopy images were taken by two blinded observers. RESULTS: The mean difference in measurement of the distance from the tip of the cervix to foetal head was 2.3mm for two hardcopy image observers,-1.96mm for two scans by the same operator and -1.52 mm for two scanners. Corresponding differences in width of opening of the internal os were 1.8, 0.44 and 0.32 mm, respectively. Interpretation of two images taken on each occasion gave similar results to those taken from three or more images. CONCLUSIONS: This method of obtaining TVS measurements from the cervix from hardcopy images that has satisfactory intra- and inter-observer error. It remains to be established whether this method will be better than Bishop score in predicting the outcome of induced or spontaneous labour. The technique appears to be suited for use in multicentre trials of TVS of the cervix at term.