Influencing surgical management in patients with carcinoma of the cervix using a T2- and ZOOM-diffusion-weighted endovaginal MRI technique.

BACKGROUND: Endovaginal MRI (evMRI) at 3.0-T with T2-weighted (T2-W) and ZOnal Oblique Multislice (ZOOM)-diffusion-weighted imaging (DWI) potentially improves the detection of stage Ia/Ib1 cervical cancer. We aimed to determine its sensitivity/specificity, document tumour-to-stromal contrast and establish the effect of imaging on surgical management. METHODS: Following ethical approval and written informed consent, 57 consecutive patients with suspected stage Ia/Ib1 cervical cancer underwent evMRI at 3.0-T using T2-W and ZOOM-DWI. Sensitivity/specificity were calculated against histopathology for two independent observers. Tumour-to-stromal contrast was determined on T2-W, and diffusion-weighted (b=800 s mm(-2)) images and apparent diffusion coefficients (ADCs) were recorded. In patients due for radical vaginal trachelectomy (RVT), change of surgical management based on imaging findings was documented. RESULTS: Sensitivity/specificity for detecting tumour was the following: reporting read 88.0/81.8%, anonymised read 92.0/81.8% (observer 1); 84.0/72.7% (observer2; median tumour volume=1.7 cm(3)). Intraobserver agreement was excellent (kappa=0.89) and the interobserver agreement was good (kappa=0.65). Tumour-to-stromal contrast was greater on ZOOM-DWI compared with T2-W images (3.35±2.36 vs 1.39±0.95; P<0.0004). Tumour and stromal ADCs were significantly different (P<0.00001). In 31 patients due for RVT, evMRI altered surgical management in 12 (38.7%) cases (10 cone-biopsy, 2 chemoradiotherapy). CONCLUSION: T2-W+ZOOM-DWI evMRI has high sensitivity/specificity for detecting stage Ia/Ib1 cervical tumours; in patients due for RVT, the surgical management was altered in ∼39%.

Outcomes of surgical management of bowel obstruction in relapsed epithelial ovarian cancer (EOC).

OBJECTIVE: To describe the outcomes of surgical management of bowel obstruction in relapsed epithelial ovarian cancer (EOC) so as to define the criteria for patient selection for palliative surgery. METHODS: 90 women with relapsed EOC underwent palliative surgery for bowel obstruction between 1992 and 2008. RESULTS: Median age at time of surgery for bowel obstruction was 57 years (range, 26 to 85 years). All patients had received at least one line of platinum-based chemotherapy. Median time from diagnosis of primary disease to documented bowel obstruction requiring surgery was 19.5 months (range, 29 days-14 years). Median interval from date of completed course of chemotherapy preceding surgery for bowel obstruction was 3.8 months (range, 5 days-14 years). Ascites was present in 38/90(42%). 49/90(54%) underwent emergency surgery for bowel obstruction. The operative mortality and morbidity rates were 18% and 27%, respectively. Successful palliation, defined as adequate oral intake at least 60 days postoperative, was achieved in 59/90(66%). Only the absence of ascites was identified as a predictor for successful palliation (p=0.049). The median overall survival (OS) was 90.5 days (range, <1 day-6 years). Optimal debulking, treatment-free interval (TFI) and elective versus emergency surgery did not predict survival or successful palliation from surgery for bowel obstruction (p>0.05). CONCLUSION: Surgery for bowel obstruction in relapsed EOC is associated with a high morbidity and mortality rate especially in emergency cases when compared to other gynaecological oncological procedures. Palliation can be achieved in almost two thirds of cases, is equally likely in elective and emergency cases but is less likely in those with ascites.

Recommendations for a standardised educational program in robot assisted gynaecological surgery: Consensus from the Society of European Robotic Gynaecological Surgery (SERGS).

BACKGROUND: The Society of European Robotic Gynaecological Surgery (SERGS) aims at developing a European consensus on core components of a curriculum for training and assessment in robot assisted gynaecological surgery. METHODS: A Delphi process was initiated among a panel of 12 experts in robot assisted surgery invited through the SERGS. An online questionnaire survey was based on a literature search for standards in education in gynaecological robot assisted surgery. The survey was performed in three consecutive rounds to reach optimal consensus. The results of this survey were discussed by the panel and led to consensus recommendations on 39 issues, adhering to general principles of medical education. RESULTS: On review there appeared to be no accredited training programs in Europe, and few in the USA. Recommendations for requirements of training centres, educational tools and assessment of proficiency varied widely. Stepwise and structured training together with validated assessment based on competencies rather than on volume emerged as prerequisites for adequate and safe learning. An appropriate educational environment and tools for training were defined. Although certification should be competence based, the panel recommended additional volume based criteria for both accreditation of training centres and certification of individual surgeons. CONCLUSIONS: Consensus was reached on minimum criteria for training in robot assisted gynaecological surgery. To transfer results into clinical practice, experts recommended a curriculum and guidelines that have now been endorsed by SERGS to be used to establish training programmes for robot assisted surgery.

Development of Peritoneal Carcinoma in women diagnosed with Serous Tubal Intraepithelial Carcinoma (STIC) following Risk-Reducing Salpingo-Oophorectomy (RRSO).

INTRODUCTION: The management of Serous Tubal Intraepithelial Carcinoma (STIC) found at the time of Risk-Reducing Salpingo-Oophorectomy (RRSO) remains unclear. We set out to analyse the incidence of peritoneal carcinomas developed after prophylactic surgery and to formulate further guidance for these patients. METHODS: This is a retrospective study of 300 consecutive RRSO performed at the Royal Marsden Hospital between January 2008 and January 2017. RESULTS: The median age at RRSO was 47.8 years (range 34 to 60 years) and median BMI was 26.2 kg/m2 (range 16 to 51 kg/m2). A total of 273 patients (91%) were tested for BRCA mutations. Of these, 124 (45.4%) had a BRCA 1 mutation, 118 (43.2%) had a BRCA 2 mutation, 2 (0.7%) had both a BRCA 1 and a BRCA 2 mutation and 29 (10.6%) had no BRCA mutation detected. Isolated STIC lesions were identified in 7 cases (2.3%) and p53 signatures in 75 cases (25%). There were five (1.6%) incidental tubal carcinomas and one (0.3%) ovarian carcinoma at the time of surgery. Two (28.6%) of the 7 patients with STIC identified following RRSO had high grade serous peritoneal carcinoma diagnosed at 53 and 75 months. One (0.3%) patient from the other 287 patients from our series with no STIC diagnosis or incidental carcinomas at RRSO developed high grade serous carcinoma of peritoneal origin after 92 months. CONCLUSION: This study demonstrates that when a STIC lesion is identified following RRSO there is a significantly higher risk of a subsequent peritoneal cancer. Although there is no published consensus in literature, we recommend that consideration should be given for long term follow-up if a STIC lesion is identified at RRSO.

Glove perforations during open surgery for gynaecological malignancies.

OBJECTIVE: To audit glove perforations at laparotomies for gynaecological cancers. SETTING: Gynaecological oncology unit, cancer centre, London. DESIGN: Prospective audit. SAMPLE: Twenty-nine laparotomies for gynaecological cancers over 3 months. METHODS: Gloves used during laparotomies for gynaecological cancer were tested for perforations by the air inflation and water immersion technique. Parameters recorded were: type of procedure, localisation of perforation, type of gloves, seniority of surgeon, operation time and awareness of perforations. MAIN OUTCOME MEASURE: Glove perforation rate. RESULTS: Perforations were found in gloves from 27/29 (93%) laparotomies. The perforation rate was 61/462 (13%) per glove. The perforation rate was three times higher when the duration of surgery was more than 5 hours. The perforation rate was 63% for primary surgeons, 54.5% for first assistant, 4.7% for second assistant and 40.5% for scrub nurses. Clinical fellows were at highest risk of injury (94%). Two-thirds of perforations were on the index finger or thumb. The glove on the nondominant hand had perforations in 54% of cases. In 50% of cases, the participants were not aware of the perforations. There were less inner glove perforations in double gloves compared with single gloves (5/139 versus 26/154; P = 0.0004, OR = 5.4, 95% CI 1.9-16.7). The indicator glove system failed to identify holes in 44% of cases. CONCLUSIONS: Glove perforations were found in most (93%) laparotomies for gynaecological malignancies. They are most common among clinical fellows, are often unnoticed and often not detected by the indicator glove system.

The use of inferior vena caval filters prior to major surgery in women with gynaecological cancer.

OBJECTIVE: To evaluate the use of inferior vena caval filters (IVCF) prior to surgery in women with gynaecological cancer and venous thromboembolism (VTE). DESIGN: Retrospective review of medical notes and electronic records. SETTING: Gynaecological oncology cancer centre. POPULATION: Women with gynaecological cancer and VTE requiring major surgery. METHODS: A retrospective analysis was performed on women treated for gynaecological malignancies who had had VTE, and an IVCF placed before major abdominal surgery were reviewed during the period 1996-2006. MAIN OUTCOME MEASURES: Safety of IVCF placement and retrieval, peri-operative morbidity and incidence of further VTE. RESULTS: The median age was 66 years (range 30-84 years). Of the 39 women, 35 (90%) women had a primary cancer diagnosis and 4 (10%) had recurrent disease. Twenty-two women had ovarian cancer, 2 had borderline ovarian tumours, 9 had uterine cancer, 5 had cervical cancer and 1 woman had concurrent ovarian and endometrial cancers. The recurrent cancers were two cervical, one ovarian and one uterine. The IVCF used were either of the permanent or retrievable type, the latter being more commonly used in younger women. All filters were placed without morbidity, and none of these women who then underwent major abdominal surgery had VTE complications. In 43.6% of women (n = 17), surgery was performed within 6 weeks of the diagnosis of VTE. All women received perioperative anticoagulation in the form of subcutaneous low-molecular-weight heparin. Three retrievable filters were uneventfully removed postoperatively. No filter-related problems occurred. CONCLUSIONS: Surgery in women with gynaecological cancer and life-threatening VTE is feasible with preoperative IVCF placement. The use of IVCF was safe with no worsening of the VTE, and without surgical or filter-related problems. A short interval between the diagnosis of VTE and surgery was not associated with increased perioperative morbidity.

Assessment of an in vitro model for laparoscopic pelvic lymphadenectomy.

An in vitro model was developed for laparoscopic pelvic lymphadenectomy. A construct validity study was performed comparing experienced laparoscopic surgeons with inexperienced trainees. Outcome measures included global and task-orientated scoring and data from electromagnetic motion analysis of hands. Marking was performed by three independent surgeons using video playback. A significant difference was found in the time taken, number of movements made and total distance travelled between the groups. Both scoring systems discriminated between the expert and inexperienced group, demonstrating the model's construct validity.

Mucinous epithelial ovarian cancer: a separate entity requiring specific treatment.

PURPOSE: Invasive mucinous carcinoma of the ovary (mucinous epithelial ovarian cancer [mEOC]) is a histologic subgroup of epithelial ovarian cancer (EOC). Chemotherapy for mEOC is chosen according to guidelines established for EOC. The purpose of this study is to determine whether this is appropriate. PATIENTS AND METHODS: Women with advanced mEOC (International Federation of Gynecology and Obstetrics stage III or IV) who underwent first-line platinum-based chemotherapy were compared with women with other histologic subtypes of EOC in a case-controlled study. RESULTS: Eighty-one patients (27 cases, 54 controls) treated with platinum-based regimens were analyzed. The response rates for cases and controls were 26.3% (95% CI, 9.2% to 51.2%) and 64.9% (95% CI, 47.5% to 79.8%), respectively (P=.01). The odds ratio for complete or partial response to chemotherapy for mEOC was 0.19 (95% CI, 0.06 to 0.66; P=.009) compared with other histologic subtypes of EOC. Median progression-free survival was 5.7 months (95% CI, 1.9 to 9.6 months) versus 14.1 months (95% CI, 12.0 to 16.2 months; P<.001) and overall survival was 12.0 months (95% CI, 8.0 to 15.6 months) versus 36.7 months (95% CI, 25.2 to 48.2 months; P<.001) for cases and controls, respectively. The hazard ratio for progression and death was 2.94 (95% CI, 1.71 to 5.07; P<.001) and 3.08 (95% CI, 1.69 to 5.6; P<.001), respectively, for mEOC patients as compared with controls. CONCLUSION: Patients with advanced mEOC have a poorer response to platinum-based first-line chemotherapy compared with patients with other histologic subtypes of EOC, and their survival is worse. Specific alternative therapeutic approaches should be sought for this group of patients, perhaps involving fluorouracil-based chemotherapy.

Serum placental-type alkaline-phosphatase levels in patients with epithelial ovarian-carcinoma.

Serum placental alkaline phosphatase (PLAP)-type immunoreactivity was measured in 190 women with epithelial ovarian malignancy, 27 women with borderline ovarian cancer and 334 control subjects with non-neoplastic or benign gynaecological disease. Smoking, ABO blood group and menopausal status affect serum concentrations of PLAP and results were corrected for these. Circulating levels were elevated in patients with cancer and increased with stage. Levels were unaltered in borderline ovarian disease. Two-year stage corrected survival analysis demonstrated a significant worsening of prognosis in patients with serum PLAP-type levels greater than the 100th centile for controls.

Serum placental-type alkaline phosphatase activity in women with squamous and glandular malignancies of the reproductive tract.

AIM: To investigate serum placental-type alkaline phosphatase (PLAP-type) activities in women with squamous and glandular malignancies of the reproductive tract using an immunoradiometric assay. METHODS: PLAP-type immunoreactivity was measured in 180 women with non-ovarian malignancies of the reproductive tract and the values were compared with those from 334 controls. The cases comprised 18 vulval, nine vaginal, 103 cervical, 46 endometrial, and five fallopian tube cancers. RESULTS: Serum PLAP-type activities were no different from controls in patients with squamous cell tumours. Women with adenocarcinoma of the cervix, endometrium, and fallopian tube had increased values: women with endometrial cancer had a median value nearly four times greater than that of controls. There was no direct correlation between PLAP-type activities and stage of disease in patients with endometrial cancer, but values reverted to normal after treatment. CONCLUSIONS: Serum PLAP-type measurements are of no value in the management of patients with squamous cell tumours of the female reproductive tract. Raised activities can, however, be found in glandular tumours, in particular endometrial cancer where serum PLAP-type measurements may be of value in predicting remission.

Low levels of amniotic fluid pregnancy specific beta-1-glycoprotein in Down's syndrome.

Amniotic fluid levels of beta-1-glycoprotein (SP1) were measured in 46 cases of Down's syndrome and compared with levels in 106 pregnancies of normal karyotype from 10 to 23 weeks of gestation. In normal pregnancies, levels rose from 87.5 iu/l at 10 weeks to a peak of 610.0 iu/l at 19 weeks of gestation. In cases of Down's syndrome, levels were reduced prior to 19 weeks of gestation (median multiple of the median, MoM = 0.75, P = 0.02). This effect was most marked prior to 16 weeks of gestation when the median multiple of the median (MoM) was 0.51 (P = 0.006). These data demonstrate that amniotic fluid levels of SP1 are low in Down's syndrome before 19 weeks of gestation.

Second trimester amniotic fluid placental alkaline phosphatase levels are low in Down's syndrome but not in other fetal abnormalities.

Second trimester amniotic fluid placental alkaline phosphatase (PLAP) immunoreactivity was measured in 756 normal pregnancies, 63 Down's syndrome pregnancies and 42 pregnancies associated with other chromosomal abnormalities. PLAP levels were significantly reduced in cases of Down's syndrome (MoM = 0.72, U = 17,565, P = 0.0002, 95% Cl = 0.63-0.88). However, there was no significant difference between other aneuploid conditions and the normals (MoM = 0.88, U = 13,289, P = 0.35, 95% CI = 0.77-1.08). PLAP is the carrier protein for immunoglobulin G. Neonates with Downs syndrome but not other chromosomal abnormalities are associated with a deficiency of IgG. These data therefore support the theory that the low IgG levels in Downs syndrome are a result of a defect in PLAP transport.

Amniotic fluid erythropoietin levels in normal and Down's syndrome pregnancies.

The aim of this study was to measure the levels of erythropoietin in amniotic fluid from normal and trisomy 21 pregnancies at 10 to 20 weeks gestation. Samples of amniotic fluid were collected from 142 women with singleton pregnancies after genetic amniocentesis; 110 had a normal fetal karyotype and 32 had trisomy 21. Erythropoietin was measured using a double antibody radioimmunoassay. Amniotic fluid erythropoietin levels in normal pregnancies increased from 10 weeks (mean 3.2 mU/ml; range < 2.0-6.3 mU/ml) to 20 weeks gestation (mean 7.9 mU/ml; range 2.0-11.5 mU/ml). There was a significant linear correlation between gestational age and erythropoietin levels (r = 0.543; P < 0.0001). For the 32 patients with trisomy 21 pregnancies the median multiple of the median (MoM) was 1.11 (range 0.42-2.1). There was no difference between erythropoietin levels in amniotic fluid from normal and Down's syndrome pregnancies (U = 2352, P = 0.75, 95% CI = -0.11, 0.18); (Mann-Whitney U-test).

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.

Comparing the learning curve for robotically assisted and straight stick laparoscopic procedures in surgical novices.

INTRODUCTION: Robotically assisted laparoscopic surgery has a different learning curve to straight stick laparoscopic surgery. The learning curve for novices is likely to be different to that for experienced surgeons. We assessed the early learning curve for trainees with 18 months or less of surgical experience. METHODS: Six surgical novices performed 120 exercises using laparoscopic instruments and a DaVinci S robot. The exercise comprised cutting out a computer-generated paper circle. Time to completion, number of instrument changes and accuracy were compared (Kruskal-Wallis test). RESULTS: Trainees required significantly less time using the robot (326 vs. 433 s; p < 0.0001); recorded fewer mistakes (1 vs. 4.5; p < 0.0001) and fewer instrument changes (1 vs. 3; p < 0.0001). Significant improvement was demonstrated in time, number of mistakes and instrument changes for robotically-assisted laparoscopic surgery. CONCLUSION: For surgical novices tested on an in vitro dexterity exercise, a robotically assisted laparoscopic system offers a shorter learning curve and improved accuracy compared to straight stick surgery.