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.

Tetraspanin CD151 is a novel prognostic marker in poor outcome endometrial cancer.

BACKGROUND: Type II cancers account for 10% of endometrial cancers but 50% of recurrence. Response rates to chemotherapy at recurrence are poor and better prognostic markers are needed to guide therapy. CD151 is a small transmembrane protein that regulates cell migration and facilitates cancer metastasis. High CD151 expression confers poor prognosis in breast, pancreatic and colorectal cancer. The prognostic significance of tetraspanin CD151 expression in poor outcome endometrial cancers was evaluated, along with oestrogen receptor (ER), progesterone receptor (PR), p53, human epidermal growth factor receptor -2 (HER-2), and CD 151 staining compared with α6ß1, α3ß1 integrins, and E-cadherin. METHODS: Tissue microarray constructed from 156 poor outcome endometrial cancers, tested with immunohistochemistry and staining correlated with clinicopathological data were used. A total of 131 data sets were complete for analysis. RESULTS: Expression of CD151 was significantly higher in uterine papillary serous and clear cell carcinoma than in grade 3 endometrioid carcinoma, sarcoma or carcinosarcoma (P<0.001). In univariate analysis, age, stage, histology type and CD151 were significant for both recurrence free (RFS) and disease specific survival (DSS). In multivariate analyses, CD151 was significant for RFS and DSS (P=0.036 and 0.033, respectively) in triple negative (ER, PR and HER-2 negative) tumours (88/131). The HER-2, p53, ER and PR were not prognostic for survival. There was strong concordance of CD151 with E-cadherin (98%), but not with α6ß1 (35%), α3ß1 staining (60%). CONCLUSION: The CD151 is a novel marker in type 2 cancers that can guide therapeutic decisions. CD151 may have an important role in tumourigenesis in some histology types.

Chloroplast DNA phylogeography of the arctic-montane species Saxifraga hirculus (Saxifragaceae).

The genetic structure of populations of an arctic-montane herb, Saxifraga hirculus (Saxifragaceae), was analysed by means of chloroplast restriction fragment-length polymorphism. Sampled populations were distributed across Europe and North America (Alaska and Colorado). There was no evidence for geographically structured genetically divergent lineages, and although no haplotypes were shared between North America and Europe, the haplotypes from different continents were intermixed on a minimum spanning tree. European populations were much more highly differentiated and had much lower levels of haplotype diversity than their Alaskan counterparts. Centres of haplotype diversity were concentrated in those Alaskan populations located outside the limits of the last (Wisconsin) glaciation, suggesting that they may have acted as refugia during the Pleistocene. It was not possible to identify putative migration routes or corresponding refugia in the European genepool. One British population, from the Pentland Hills, was genetically very distant from all the others, for reasons that are as yet unknown.

Population differentiation of Potamogeton pectinatus in the Baltic Sea with reference to waterfowl dispersal.

Forty populations of Potamogeton pectinatus L. were sampled from around the Baltic Sea basin. Analysis of 62 ISSR 'loci' showed that the number of clones per population is very variable but shows a tendency to decrease with latitude. Analysis of molecular variance revealed that, overall, just over half the variability is stored within populations and just under half between them (phi(ST) 0.496). In pairwise comparisons, most populations are significantly differentiated. Genetic distance between populations, as measured by phi(ST), increases with geographical distance. Levels of population differentiation, however, are lower on the southeastern Swedish coast than elsewhere, a reduction correlated with the importance of this area as a staging post for the massive migrations of waterfowl from arctic Russia and western Siberia. Cumulative plots of phi(ST) against geographical distance along this coast suggest that, although it does not prevent significant population differentiation, bird traffic reduces it over distances of 150-200 km.

Investigation of women with endometrial carcinoma using serum vascular endothelial growth factor (VEGF) measurement.

This study assessed whether serum VEGF measurement in women presenting with endometrial cancer could predict advanced stage disease. Preoperative sera from 37 women undergoing laparotomy for suspected endometrial cancer were assayed for VEGF, CA125 and platelet count. Significant positive correlation was shown between VEGF and platelet levels (P = 0.003, r = 0.477). However, no correlation was demonstrated between VEGF and stage overall, and no significant difference was shown between those with early (stage 1A/1B, n = 20) compared to those with advanced (stage >1B, n = 13) or disseminated (stage >2, n = 7) disease. Serum VEGF measurement was not beneficial in the preoperative assessment of stage in patients with endometrial carcinoma. Strong correlation with platelet levels suggests that this is one of the sources of VEGF measured.

Is conservative treatment for adenocarcinoma in situ of the cervix safe?

OBJECTIVE: To determine the long term results of treatment of adenocarcinoma in situ by conisation of the cervix using survival analysis. DESIGN: A retrospective study in six teaching hospitals in North West Thames. POPULATION: Eighty-five women with a histological diagnosis of adenocarcinoma in situ of the cervix in punch or cone biopsy were identified from pathology and clinical databases. RESULTS: In one patient a small focus of adenocarcinoma in situ was found in a cervical polyp. Subsequent cytology was normal and no further treatment was undertaken. The 84 remaining women underwent diathermy loop, cold knife cone biopsy, laser cone biopsy, or needle excision of the transformation zone. A hysterectomy or second conisation was performed in 31/84 women (36.9%) as part of the initial treatment. In all, nine (10.6%) had early invasive lesions of which four were squamous. Fifty-nine patients were treated conservatively following one or two conisations (median follow up 78 weeks, range 0-543 weeks). One had a subsequent hysterectomy for menorrhagia. Five women have undergone treatment for suspected recurrence, a 21.5% cumulative rate of further treatment by four years. The cumulative rate of histologically proven recurrence after conservative management was 4.3% at one year and 15% at four years. CONCLUSIONS: In those cases with clear margins in the cone biopsy, there is a place for conservative management of a selected group of patients who wish to preserve fertility. However, 16.7% of these will require further treatment after four years because of recurrent cytological abnormalities. Women who opt for conservative management should undergo regular, long term surveillance in a colposcopy clinic. Among those women with involved margins in the initial cone biopsy, there is a high incidence of residual disease. A second cone biopsy may be appropriate 'definitive treatment' for young women who wish to preserve their fertility if the margins of the second biopsy are clear and there is no evidence of invasion. Even among those for whom a hysterectomy is the proposed 'definitive treatment', a second cone biopsy may be required before hysterectomy to avoid inappropriate treatment of an occult invasive lesion.

Six year survey of screening for Down's syndrome by maternal age and mid-trimester ultrasound scans.

OBJECTIVE: To assess the effectiveness of antenatal screening for Down's syndrome by maternal age and routine mid-pregnancy ultrasound scanning. DESIGN: Retrospective six year survey. SETTING: Maternity units of a district general hospital. SUBJECTS: Pregnant women booked for delivery in hospital between 1 January 1993 and 31 December 1998. MAIN OUTCOME MEASURES: All cases of Down's syndrome occurring in district identified from regional congenital anomaly register and cytogenetic laboratory records. Women's case notes were examined to identify indication for karyotyping, gestation at diagnosis, and outcome of pregnancy. RESULTS: 31 259 deliveries occurred during study period, and 57 cases of Down's syndrome were identified, four in failed pregnancies and 53 in ongoing pregnancies or in neonates. The analysis was confined to ongoing pregnancies or liveborn children. Invasive antenatal tests were performed in 6.6% (2053/31 259), and 68% (95% confidence interval 56% to 80%) of cases of Down's syndrome were detected antenatally, giving a positive predictive value of 1.8%. There were 17 undetected cases, and in seven of these the women had declined an offer of invasive testing. In women aged less than 35 years the detection rate was 53% (30% to 76%). Most of the cases detected in younger women followed identification of ultrasound anomalies. CONCLUSIONS: The overall detection rate was considerably higher than assumed in demonstration projects for serum screening. As a result, the benefits of serum screening are much less than supposed. Before any new methods to identify Down's syndrome are introduced, such as nuchal translucency or first trimester serum screening, the techniques should be tested in properly controlled trials.

Glandular abnormalities on cervical smear: a study to compare the accuracy of cytological diagnosis with underlying pathology.

The interpretation of glandular abnormalities detected by cervical smear provides a diagnostic dilemma. This study aims to compare the accuracy of cytological diagnosis with underlying pathology so that guidelines for the investigation and management of abnormal glandular smears may be formulated. A retrospective review of 150 women with glandular abnormalities reported on cervical smear collected over 12 months from 1996 in a University hospital was performed. Smears were graded by the initial report into 3 groups, dependent on the severity of abnormality. Investigation, treatment and subsequent 3-year follow-up were recorded. The accuracy of prediction for a significant neoplastic or preneoplastic glandular pathology only was 0% with mild, 9% (3/35) with moderate, and 24% (9/38) with severe abnormalities. When squamous lesions were included, the chance of finding any dysplastic squamous or glandular abnormality was 16% (12/77), 51% (18/35) and 82% (31/38), respectively, following a smear showing a suspected glandular abnormality only. Our results highlight the poor specificity of predicting glandular neoplasia or preneoplasia from cervical smears, with a final diagnosis of high grade CIN in 35% (17/49) of patients with dyskaryotic glandular cytological changes only and 83% (20/24) where concomitant squamous dyskaryosis was reported. The reporting of reactive or minor changes in endocervical cells was of no diagnostic value. Management protocols for moderate and severe glandular abnormalities should include visualisation and biopsy of the uterine cavity to exclude endometrial neoplasia.

Interval cervical cancer following treatment for cervical intraepithelial neoplasia.

The objective of this study was to determine whether those women who developed cervical cancer following treatment for preinvasive disease had common features in their history which could identify those at increased risk of progression and therefore be used to modify management protocols. A retrospective case note review from clinical and histopathologic records was undertaken at a teaching hospital in Wessex, Southern England. The review included 33 women diagnosed with cervical carcinoma between 1985 and 1996 who had previously undergone treatment for cervical intraepithelial neoplasia (CIN) or cervical glandular intraepithelial neoplasia (CGIN). The diagnosis prior to treatment was CIN 3 in 19 cases, CGIN 3 in 2 cases, CIN 2 in 9 cases (97% high grade CIN/CGIN) and CIN 1 in 1 case. At primary treatment, among those treated by knife cone biopsy or Large Loop Excision of the Transformation Zone (LLETZ), and for whom the margins of the treatment specimen were reported, 14 out of 15 had incomplete margins. Local ablation (in which completeness of excision could not be histologically assessed) was performed in 12 cases. In 58% (19/33) of cases, the patient was 40 years or older at the time of initial treatment. Fifteen women had one or more negative smears after treatment, of which only 6 had transformation zone sampling. The interval between treatment of CIN/CGIN and diagnosis of invasion ranged from 8 to 216 months. (mean 40.4 months), with 67% of cases of invasive cancer occurring within 5 years of treatment for CIN/CGIN and 94% within 10 years. Screen detection was achieved in 91% (30/33) of cases with 53% diagnosed while stage 1A. In conclusion, most treatment screen detection of invasive disease at an early (and often microinvasive) stage was achieved for most patients, although a third of patients were diagnosed more than 5 years after initial treatment. The data suggest the need to follow up longer than 5 years when there are risk factors such as incomplete excision of high grade CIN/CGIN and in women over 40 years of age at the time of initial diagnosis.

Can flexible sigmoidoscopy predict need for colorectal surgery in ovarian carcinoma?

INTRODUCTION: It is difficult to predict which patients with ovarian cancer will require bowel surgery. We propose that sigmoidoscopy performed by an experienced colorectal surgeon could predict the need for bowel resection as part of optimum cytoreduction by assessment of rigidity and encasement of the rectosigmoid colon or mucosal involvement. Laparotomy may then be performed electively in collaboration with a colorectal surgeon after administration of bowel preparation. METHODS: In a prospective study 30 patients undergoing surgery for a high suspicion of ovarian malignancy and with at least two of either a complex pelvic mass on ultrasound, elevated CA125 or ascites were studied. Flexible sigmoidoscopy performed at time of admission was reported as "clear bowel", "external compression only" or "mucosal involvement" with the recommendation to "avoid resection" or "may need resection". RESULTS: Sigmoidoscopy was completed in all patients and was well tolerated. Satisfactory preparation and evaluation was possible in 70% and did not delay definitive surgery. 67% (20/30) of cases proved to have ovarian carcinoma. Overall prediction to avoid resection was correct in 21/25 and to resect in 5/9 with accurate prediction in those with ovarian cancer of 17/20 cases. This included 3/4 sigmoid colectomies for ovarian malignancy as part of an optimum debulking procedure. Sigmoidoscopy was more accurate than relying on a history of change in bowel habit alone in predicting the need for bowel resection. CONCLUSIONS: Sigmoidoscopy was shown to be a practical procedure, causing no significant morbidity in patients with ovarian carcinoma. In evaluating a pelvic mass it can exclude primary colorectal pathology and impending obstruction. Flexible sigmoidoscopy correctly identified the majority of cases which required colorectal surgery and allowed an optimal resection to take place as a planned procedure.

Topical antiseptic agent after large loop excision of the transformation zone: results of a randomised controlled trial.

One hundred patients undergoing large loop excision of the transformation zone (LLETZ) were randomised to receive postoperative local treatment with sultrin (sulphathiazole 3.42%, sulphacetamide 2.86%, sulphabenzamide 3.7%) pessaries: one pessary twice daily for 5 days, or no treatment. Outcome measures included duration and severity of vaginal bleeding, discharge, pelvic pain, need for oral antibiotic therapy and unplanned hospital admission. There was no significant difference in the severity of symptoms in the treatment and control groups for bleeding, discharge or pain, averaged over the study period. Postoperative morbidity following LLETZ was frequent but mild. Use of prophylactic antiseptic agents is not recommended.

A randomised placebo controlled trial of loop diuretics in moderate/severe pre-eclampsia, following delivery.

Nineteen patients with pre-eclampsia were randomised to receive 40 mg of frusemide or placebo by mouth daily for 7 days in the first post-partum week. Outcome measures included mean and maximum blood pressure, the need for additional antihypertensive treatment during that period and mean length of hospital stay. There were no statistically significant differences in outcome between the treatment and placebo groups although there was a trend to more rapid lowering of blood pressure following delivery in those receiving frusemide.