Laparoscopic Ovarian Transposition and Ovariopexy for Fertility Preservation in Patients Treated with Pelvic Radiotherapy with or without Chemotherapy.

BACKGROUND: Preservation of fertility in cancer patients of reproductive age is a concern for both the patient and the clinician. In this study, we aimed to study the effectiveness of laparoscopic ovarian transposition or ovariopexy in preserving ovarian function in women undergoing pelvic radiotherapy with or without chemotherapy for pelvic tumours. METHODS: The records of patients who underwent laparoscopic ovarian transposition or ovariopexy prior to pelvic radiation therapy between 2002 and 2018 were reviewed retrospectively. RESULTS: Thirty-nine women or adolescent girls with a diagnosis of cervical cancer (n=15), Hodgkin's lymphoma (n=6) or other types of pelvic tumours (n=18) were included in the study. The majority of patients had bilateral (n=25) or unilateral (n=8) ovarian transposition prior to radiotherapy. Nine out of 10 (90%) patients with soft tissue tumors, Ewing sarcoma or ependymoma, five out of seven (71.4%) patients with Hodgkin's lymphoma, two patients (100%) with rectal and anal cancer, and six out of 15 (40%) with cervical cancer retained ovarian function. Patients with cervical cancer, those who received concomitant chemotherapy and those older than 30 years were more likely to experience ovarian failure. Five patients conceived spontaneously and two women had four live births. CONCLUSION: Laparoscopic repositioning of the ovaries out of the radiation field in order to protect ovarian function in patients receiving radiotherapy appears to be effective in the majority of patients. The procedure seems safe and should be considered either as a sole procedure or in association with other fertility preservation methods prior to pelvic radiotherapy.

Improved Survival from Ovarian Cancer in Patients Treated in Phase III Trial Active Cancer Centres in the UK.

AIMS: Ovarian cancer is the principal cause of gynaecological cancer death in developed countries, yet overall survival in the UK has been reported as being inferior to that in some Western countries. As there is a range of survival across the UK we hypothesised that in major regional centres, outcomes are equivalent to the best internationally. MATERIALS AND METHODS: Data from patients treated in multicentre international and UK-based trials were obtained from three regional cancer centres in the UK; Manchester, University College London and Leeds (MUL). The median progression-free survival (PFS) and overall survival were calculated for each trial and compared with the published trial data. Normalised median survival values and the respective 95% confidence intervals (ratio of pooled MUL data to trial median survival) were calculated to allow inter-trial survival comparisons. This strategy then allowed a comparison of median survival across the UK, in three regional UK centres and in international centres. RESULTS: The analysis showed that the trial-reported PFS was the same in the UK, in the MUL centres and in international centres for each of the trials included in the study. Overall survival was, however, 45% better in major regional centre-treated patients (95% confidence interval 9-73%) than the median overall survival reported in UK trials, whereas the median overall survival in MUL centres equated with that achieved in international centres. CONCLUSION: The data suggest that international survival statistics are achieved in UK regional cancer centres.

Benchmarking of surgical complications in gynaecological oncology: prospective multicentre study.

OBJECTIVE: To explore the impact of risk-adjustment on surgical complication rates (CRs) for benchmarking gynaecological oncology centres. DESIGN: Prospective cohort study. SETTING: Ten UK accredited gynaecological oncology centres. POPULATION: Women undergoing major surgery on a gynaecological oncology operating list. METHODS: Patient co-morbidity, surgical procedures and intra-operative (IntraOp) complications were recorded contemporaneously by surgeons for 2948 major surgical procedures. Postoperative (PostOp) complications were collected from hospitals and patients. Risk-prediction models for IntraOp and PostOp complications were created using penalised (lasso) logistic regression using over 30 potential patient/surgical risk factors. MAIN OUTCOME MEASURES: Observed and risk-adjusted IntraOp and PostOp CRs for individual hospitals were calculated. Benchmarking using colour-coded funnel plots and observed-to-expected ratios was undertaken. RESULTS: Overall, IntraOp CR was 4.7% (95% CI 4.0-5.6) and PostOp CR was 25.7% (95% CI 23.7-28.2). The observed CRs for all hospitals were under the upper 95% control limit for both IntraOp and PostOp funnel plots. Risk-adjustment and use of observed-to-expected ratio resulted in one hospital moving to the >95-98% CI (red) band for IntraOp CRs. Use of only hospital-reported data for PostOp CRs would have resulted in one hospital being unfairly allocated to the red band. There was little concordance between IntraOp and PostOp CRs. CONCLUSION: The funnel plots and overall IntraOp (≈5%) and PostOp (≈26%) CRs could be used for benchmarking gynaecological oncology centres. Hospital benchmarking using risk-adjusted CRs allows fairer institutional comparison. IntraOp and PostOp CRs are best assessed separately. As hospital under-reporting is common for postoperative complications, use of patient-reported outcomes is important. TWEETABLE ABSTRACT: Risk-adjusted benchmarking of surgical complications for ten UK gynaecological oncology centres allows fairer comparison.

Predictors of complications in gynaecological oncological surgery: a prospective multicentre study (UKGOSOC-UK gynaecological oncology surgical outcomes and complications).

BACKGROUND: There are limited data on surgical outcomes in gynaecological oncology. We report on predictors of complications in a multicentre prospective study. METHODS: Data on surgical procedures and resulting complications were contemporaneously recorded on consented patients in 10 participating UK gynaecological cancer centres. Patients were sent follow-up letters to capture any further complications. Post-operative (Post-op) complications were graded (I-V) in increasing severity using the Clavien-Dindo system. Grade I complications were excluded from the analysis. Univariable and multivariable regression was used to identify predictors of complications using all surgery for intra-operative (Intra-op) and only those with both hospital and patient-reported data for Post-op complications. RESULTS: Prospective data were available on 2948 major operations undertaken between April 2010 and February 2012. Median age was 62 years, with 35% obese and 20.4% ASA grade ⩾3. Consultant gynaecological oncologists performed 74.3% of operations. Intra-op complications were reported in 139 of 2948 and Grade II-V Post-op complications in 379 of 1462 surgeries. The predictors of risk were different for Intra-op and Post-op complications. For Intra-op complications, previous abdominal surgery, metabolic/endocrine disorders (excluding diabetes), surgical complexity and final diagnosis were significant in univariable and multivariable regression (P<0.05), with diabetes only in multivariable regression (P=0.006). For Post-op complications, age, comorbidity status, diabetes, surgical approach, duration of surgery, and final diagnosis were significant in both univariable and multivariable regression (P<0.05). CONCLUSIONS: This multicentre prospective audit benchmarks the considerable morbidity associated with gynaecological oncology surgery. There are significant patient and surgical factors that influence this risk.

Patient-reporting improves estimates of postoperative complication rates: a prospective cohort study in gynaecological oncology.

BACKGROUND: Most studies use hospital data to calculate postoperative complication rates (PCRs). We report on improving PCR estimates through use of patient-reporting. METHODS: A prospective cohort study of major surgery performed at 10 UK gynaecological cancer centres was undertaken. Hospitals entered the data contemporaneously into an online database. Patients were sent follow-up letters to capture postoperative complications. Grade II-V (Clavien-Dindo classification) patient-reported postoperative complications were verified from hospital records. Postoperative complication rate was defined as the proportion of surgeries with a Grade II-V postoperative complication. RESULTS: Patient replies were received for 1462 (68%) of 2152 surgeries undertaken between April 2010 and February 2012. Overall, 452 Grade II-V (402 II, 50 III-V) complications were reported in 379 of the 1462 surgeries. This included 172 surgeries with 200 hospital-reported complications and 231 with 280 patient-reported complications. All (100% concordance) 36 Grade III-V and 158 of 280 (56.4% concordance) Grade II patient-reported complications were verified on hospital case-note review. The PCR using hospital-reported data was 11.8% (172 out of 1462; 95% CI 11-14), patient-reported was 15.8% (231 out of 1462; 95% CI 14-17.8), hospital and verified patient-reported was 19.4% (283 out of 1462; 95% CI 17.4-21.4) and all data were 25.9% (379 out of 1462; 95% CI 24-28). After excluding Grade II complications, the hospital and patient verified Grade III-V PCR was 3.3% (48 out of 1462; 95% CI 2.5-4.3). CONCLUSION: This is the first prospective study of postoperative complications we are aware of in gynaecological oncology to include the patient-reported data. Patient-reporting is invaluable for obtaining complete information on postoperative complications. Primary care case-note review is likely to improve verification rates of patient-reported Grade II complications.

Risk of epithelial ovarian cancer in asymptomatic women with ultrasound-detected ovarian masses: a prospective cohort study within the UK collaborative trial of ovarian cancer screening (UKCTOCS).

OBJECTIVE: To estimate the risk of primary epithelial ovarian cancer (EOC) and slow growing borderline or Type I and aggressive Type II EOC in postmenopausal women with adnexal abnormalities on ultrasound. METHODS: This was a prospective cohort study in the ultrasound group of the UK Collaborative Trial of Ovarian Cancer Screening of postmenopausal women with ultrasound-detected abnormal adnexal (unilocular, multilocular, unilocular solid and multilocular solid, solid) morphology on their first scan. Women were followed up through the national cancer registries and by postal questionnaires. Absolute risks of EOC and borderline, Type I and Type II EOC within 3 years of initial scan were calculated. RESULTS: Of 48 053 women who underwent ultrasound examination and had complete scan data, 4367 (9.1% (95% CI, 8.8-9.3%)) had abnormal adnexal morphology. Median follow-up was 7.09 (25(th) -75(th) centiles, 6.03-7.92) years. Forty-seven (32 borderline or Type I, 15 Type II) were diagnosed with EOC. The overall absolute risk of EOC associated with abnormal adnexal morphology was 1.08% (95% CI, 0.79-1.43%); for borderline and Type I it was 0.73% (95% CI, 0.5-1.03%); and for Type II it was 0.34% (95% CI, 0.33-0.79%). In the subgroup (n = 741) with solid elements (unilocular solid, multilocular solid and solid) overall absolute risk was 4.45% (95% CI, 3.08-6.20%), for borderline and Type I it was 3.1% (95% CI, 1.9-4.6%) and for Type II it was 1.3% (95% CI, 0.6-2.4%). 11 982 women had both ovaries visualized and normal annual scans throughout the 3-year follow-up period. In this group, no borderline or Type I and eight Type II cancers were diagnosed. CONCLUSION: Asymptomatic postmenopausal women with ultrasound-detected adnexal abnormalities with solid elements have a 1 in 22 risk for EOC. Despite the higher prevalence of Type II EOC, the risk of borderline or Type I cancer in women with ultrasound abnormalities seems to be higher than does the risk of Type II cancer. This has important immediate implications for patients with incidental adnexal findings as well as for any future ultrasound-based screening.

Total laparoscopic hysterectomy in morbidly obese women with endometrial cancer anaesthetic and surgical complications.

OBJECTIVE: To assess the feasibility, associated anaesthetic and surgical morbidity in all morbidly obese women with endometrial cancer treated with total laparoscopic hysterectomy bilateral salpingo-oophorectomy (TLHBSO). STUDY DESIGN: Data was collected prospectively and analysed retrospectively on all morbidly obese women who had TLHBSO between February 2003 and January 2007. RESULTS: One case was converted to laparotomy. The mean postoperative stay was 4.04 (3-7) days. The only postoperative surgical complication was an incisional port site hernia. Comorbidities were present in 76% (26/34) of women, 29% (10/34) had a single comorbid condition, and 26% (9/34) had two. A further 21% (7/34) had more than two. There were no major anaesthetic complications. Patients with a BMI > 50 required ventilation with high airway pressure despite using ventilatory strategies to keep them to a minimum. CONCLUSION: TLHBSO in the obese population is safe in the hands of experienced surgeons and anaesthetists. The safety of a total laparoscopic approach in the surgical management of uterine cancer remains to be demonstrated in prospective randomised trials.

Enhanced repair of DNA interstrand crosslinking in ovarian cancer cells from patients following treatment with platinum-based chemotherapy.

Despite high tumour response rates to platinum-based chemotherapy in ovarian cancer survival is poor due to the emergence of drug resistance. Mechanistic studies in clinical material have been hampered by the unavailability of sensitive methods to detect the critical drug-induced effects in individual cells. A modification of the single cell gel electrophoresis (comet) assay allows the sensitive detection of DNA interstrand crosslinking in both tumour and normal cells derived directly from clinical material. Tumour cells isolated from 50 ovarian cancer patients were treated ex vivo with 100 microM cisplatin for 1 h and crosslink formation and repair (unhooking) measured. No significant difference in the peak level of crosslinking in tumour cells was observed between patients who were either newly diagnosed or previously treated with platinum-based therapy, or between tumour and mesothelial cells from an individual patient. This indicates no difference in cellular mechanisms such as drug transport or detoxification. In contrast, the percentage repair (unhooking) of DNA interstrand crosslinks was much greater in the group of treated patients. At 24 h in the 36 newly diagnosed patient tumour samples, only one gave >50% repair and 23 gave <10% repair; however, 19 out of 22 treated patient samples gave >10% repair and 14 showed >50% repair. The estimated median difference (newly diagnosed minus treated) was -52 (95% CI -67 to -28), and the P-value from a Mann-Whitney test was <0.001. In eight patients, it was possible to obtain tumour samples prior to any chemotherapy, and also on relapse or at interval debulking surgery following platinum-based chemotherapy. In these patients, the mean % repair prior to therapy was 2.85 rising to 71.23 following treatment. These data demonstrate increased repair of DNA interstrand crosslinks in ovarian tumour cells following platinum therapy which may contribute to clinical acquired resistance.

Mullerian adenosarcoma of uterine cervix: report of three cases and review of literature.

BACKGROUND: Mullerian adenosarcoma of the uterine cervix is a rare tumor seen in young women of reproductive age group. It presents as cervical polyps and is a low-grade malignancy with a tendency for local recurrence. Diagnosis can be difficult since it can easily be mistaken for benign polyps, both clinically and pathologically. CASE: We present three cases of adenosarcoma of the cervix presenting as cervical polyps and review the clinical and pathological features of these tumors. CONCLUSION: Adenosarcoma of the cervix should be ruled out especially in women presenting with recurrent cervical polyps. A careful histological examination is mandatory, important prognostic factors being myometrial invasion and sarcomatous overgrowth. Distant metastasis is very rare and therapy can be tailored to suit patient's needs but long term follow-up is essential.

The association between polycystic ovaries and endometrial cancer.

BACKGROUND: Women with polycystic ovary syndrome (PCOS) are assumed to be at increased risk of endometrial cancer (EC), albeit of a more differentiated type with better prognosis than in normal women. This study was designed to test these assumptions, as evidence for them is lacking. METHODS: The prevalence of polycystic ovaries (PCO), as a marker of PCOS, was investigated in ovarian sections from 128 women with EC and 83 with benign gynaecological conditions. The expression of the prognostic markers p53, Ki67, Bcl2 and cyclin D1 was also investigated by immunohistochemistry in endometrial tumours from 11 women with PCO and 16 with normal ovaries. RESULTS: Overall, PCO were similarly prevalent in women with EC (8.6%) and benign controls (8.4%); however, in women aged <50 years, PCO were more prevalent in women with EC (62.5 versus 27.3%, P = 0.033). Cyclin D1-expressing endometrial tumours tended to be more prevalent in women with PCO compared to normal ovaries (36.4 versus 6.25%, respectively, P = 0.071). Bcl2-, p53- and Ki67-expressing tumours were similarly prevalent. CONCLUSIONS: The association between PCOS and EC appears confined to premenopausal women. The tendency for cyclin D1-expressing endometrial tumours to be more prevalent in women with PCO challenges the assumption that EC prognosis is improved in women with PCOS.

Primary mucinous carcinoid tumour of the ovary: a case report.

Primary ovarian carcinoid tumours of the ovary are rare and represent less than 0.1% of ovarian malignancy. The evidence to guide treatment and prognosis of these tumours is limited. We report a case of primary ovarian mucinous carcinoid tumour, of the atypical category, in a 34-year-old nulliparous woman. Only three such cases have previously been reported. At four years from presentation, she has no signs of metastatic disease, despite delayed primary surgery and then initial conservative management. At present surgical excision with close follow-up appears to be the management of choice. This case adds to the body of evidence and demonstrates a possible good prognosis with non-aggressive behaviour in the atypical mucinous carcinoid group.

Total laparoscopic hysterectomy as a primary surgical treatment for endometrial cancer in morbidly obese women.

To evaluate the feasibility of total laparoscopic hysterectomy as the primary treatment for endometrial cancer in morbidly obese women, an audit was carried out during an 18-month period in a tertiary referral centre for gynaecological oncology. Four women who had laparoscopic surgery were compared with a similar cohort who had open surgery. The mean operating time was equivalent, without evidence of excess morbidity with the laparoscopic approach. However, inpatient stay was longer with open versus laparoscopic surgery (11.5 vs 4 days). Laparoscopic surgery is safe to use in morbidly obese women with endometrial cancer.

A study of blood cross-matching requirements for surgery in gynecological oncology: improved efficiency and cost saving.

The objective of this study was to design and implement a maximum surgical blood order schedule (MSBOS) within a specialist gynecological oncology department in a tertiary referral center and evaluate its impact on the cross-match to transfusion ratio (CTR). A retrospective case note audit was undertaken to identify common operations performed within the unit and their transfusion requirements. The efficiency of blood usage was assessed using the CTR, and an MSBOS was devised and implemented. A prospective audit of preoperative blood cross-matching and subsequent blood usage was then performed for consecutive elective operations in the unit, to assess the effect of the MSBOS. The retrospective study of 222 cases demonstrated a CTR of 2.25 equivalent to 44% usage of cross-matched blood. Ninety two percent of operations performed within the unit could be incorporated into an MSBOS. The prospective study of 207 cases demonstrated a significantly reduced CTR of 1.71 or 59% blood usage (chi2 = 12.4, P < 0.001). This equates to a saving of 102 units of blood over the 15 months prospective audit. Protocol adherence was 77%. No patient was adversely affected by the adoption of the MSBOS. We conclude that an MSBOS can be safely introduced into a gynecological oncology department resulting in significant financial savings.

Radical trachelectomy in early stage carcinoma of the cervix: outcome as judged by recurrence and fertility rates.

The recurrence and fertility rates in 30 women undergoing radical trachelectomy for early stage invasive cervical cancer at St Bartholomew's and Royal Marsden Hospital were reviewed. There were no recurrences, and the mean follow up was 23 months (range 1-64 months). Of 13 women trying to have a baby, eight had conceived with a total of 14 pregnancies and nine live births. Two were still trying and three were experiencing sub-fertility. There were seven premature deliveries and one late miscarriage. Six of the preterm births and the late miscarriage were associated with prelabour spontaneous rupture of membranes. This conservative yet locally radical procedure for a highly selected group of women who wished to preserve their fertility appears to offer a safe alternative to radical hysterectomy in early invasive cervical cancer.

Cervical cancer detection by hybrid capture and evaluation of local risk factors.

UNLABELLED: The city of Recife, northeastern Brazil, is reported to have the highest incidence of cervical cancer worldwide (83.2/100000 women). OBJECTIVE: To evaluate the efficacy of Hybrid Capture I (HC I) in cervical cancer detection and some risk factors in Recife. METHOD: Cervical scrapes for HC I analysis followed by colposcopy were collected from 140 women (70 with cervical cancer and 70 with normal cervix) from three screening services in Recife. RESULT: HC I sensitivity and specificity were 82.9 and 41.4%, respectively. The odds ratios for cervical cancer when Gesta > or = 5 and vaginal parity > or = 4 were, respectively, 5.30 and 4.27. CONCLUSION: HC I is a moderately sensitive method to detect cervical cancer, but it does not seem to be useful as a primary screening tool for it's low specificity. Early pregnancy, high Gesta/Para and living in rural areas were important local risk factors.

Quantitative detection of oncogenic HPV DNA using hybrid capture to triage borderline and mildly dyskaryotic Papanicolaou smears.

OBJECTIVE: To investigate the use of hybrid capture to triage borderline and mildly abnormal PAP smears to either colposcopy or continued cytological surveillance. METHOD: A prospective cross-sectional study of 207 women with either mild or borderline dyskaryosis referred to the colposcopy clinic at the Whittington Hospital, London was done. Quantitative detection of oncogenic human papillomavirus deoxyribose nucleic acid was performed using the solution hybridization technique Hybrid Capture I (Digene Diagnostics). Positive or negative hybrid capture results were compared to colposcopically directed punch biopsy or loop excision of the transformation zone. RESULTS: Hybrid capture correctly predicted 1/1 micro-invasive cancers, 23/24 CIN 3 and 20/24 CIN 2, giving a sensitivity to detect significant disease of CIN 2 or above of 90%. For CIN 1, 37/66 were HPV positive making the sensitivity to detect all grades of CIN 70%. Of women with a normal cervix, 39/92 were HPV positive and in total 58% of the women were HPV positive and would have been referred to colposcopy. CONCLUSIONS: Hybrid capture was a simple solution hybridization method which provided a sensitive method of detecting CIN 2 and above lesions in women with minor PAP smear abnormalities. However, the sensitivity for CIN 1 and the specificity were low, meaning that further improvements in the technique are needed before it can be used as a triage strategy.

Cervicography to triage women with borderline or mild dyskaryotic cervical PAP smears.

OBJECTIVE: To evaluate six years experience using cervicography to triage women with borderline or mildly dyskaryotic PAP smears to either immediate colposcopy or cytological surveillance. METHOD: Retrospective study of 1,436 women referred to the cervicography clinic of the Whittington Hospital, London. Women with suspicious cervigrams were examined colposcopically and biopsied. Women with normal appearances at cervicography were followed-up with cytology over a period of a least two years. RESULTS: Cervicography detected 281 out of 307 women with CIN 2/3 and 215 out of 264 women with CIN 1. The sensitivity of cervicography to detect CIN 1, 2 or 3 in women with minor PAP smear abnormalities was 92%. The specificity was 39% and 847 (59%) of the women were referred for colposcopy; 215 (15%) were lost to follow-up. CONCLUSIONS: Cervicography was a sensitive method to detect CIN in women with mild or borderline dyskaryosis on their PAP smears. However, the low specificity meant that a high proportion of the women were referred for colposcopy, and a significant proportion of women were lost to follow-up. Thus cervicography is not an efficient strategy for managing women with minor PAP smears abnormalities.

Pathogenesis of telangiectasia in scleroderma.

Scleroderma (progressive systemic sclerosis) is a systemic autoimmune disorder characterised by skin sclerosis, calcinosis and changes in microvasculature. The etiology of the disease is unknown but both genetic and environmental factors have been implicated. Telangiectasia (macroscopically visible dilated skin vessels) occurring primarily on the hands and face, are a prominent feature in scleroderma and are present in the majority of patients. Similarly, telangiectasia are found in patients with hereditary hemorrhagic telangiectasia (HHT), a mutational disorder of the germline genes endoglin and ALK-1, members of the TGFbeta receptor family, expressed on endothelial cells. Our study investigated the number, distribution and microscopic characteristics of telangiectasia in both limited (n = 29) and diffuse scleroderma (n = 9) and compared findings with 3 patients with HHT. In limited scleroderma, the mean number of telangiectasia (hand and face) was 36 (0-150) compared with 23 (0-135) in diffuse scieroderma. A significant correlation was observed between the number of telangiectasia on the face and on the hands (p = 0.014). The total number of telangiectasia correlated significantly with the disease duration (p = 0.009). The spatial distribution of the telangiectasia appeared to be random on both hands and foreface in contrast with the distribution of subcutaneous calcification of the hands which occurred predominantly on the distal and flexor surfaces of the first, second and fifth digits. Nailfold microscopic capillaroscopy was performed on 12 patients. No significant correlation was observed between capillary diameter or density and with total number of telangiectasia observed macroscopically. The distribution and microscopic appearance of telangiectasia in scleroderma appeared very similar to those observed in HHT. In view of these similarities we therefore conclude that telangiectactic development in scleroderma may be associated with disorders of the TGFb receptor family proteins found on the microvasculature.

The Polarprobe--emerging technology for cervical cancer screening.

The Polarprobe is a portable non invasive electronic device designed for the detection of cervical precancer and cancer. It measures both electrical and optical properties of cervical tissue to allow a real time comparison with a databank of previously determined cervical tissue types. The need for additional tests to augment or even replace the Papanicolaou smear has partly prompted its development. Indeed it has been shown to be associated with less pain and anxiety than the smear and has the capability of encouraging women to attend for screening. Some of the preliminary clinical trials on the Polarprobe are reported as well as the ongoing developments and modifications to the device.