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.

Sertoli-Leydig Cell Tumour and DICER1 Mutation: A Case Report and Review of the Literature.

Sertoli-Leydig cell tumours of the ovary (SLCT) are rare tumours predominantly caused by mutations in the DICER1 gene. We present a patient with a unilateral SLCT who had an underlying germline DICER1 gene mutation. We discuss the underlying pathology, risks, and screening opportunities available to those with a mutation in this gene as SLCT is only one of a multitude of other tumours encompassing DICER1 syndrome. The condition is inherited in an autosomal dominant fashion. As such, genetic counselling is a key component of the management of women with SLCT.

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.

Surgical practice of UK gynaecological oncologists in the treatment of primary advanced epithelial ovarian cancer (PAEOC): a questionnaire survey.

OBJECTIVE: To assess the routine surgical practices of consultant gynaecological oncologists (CGOs) in the United Kingdom in their management of primary advanced (FIGO stages III and IV) epithelial ovarian cancer (PAEOC). METHODS: The same anonymised questionnaire was sent twice to all consultant gynaecological oncologists (CGOs) working in the UK. The questions enquired about surgical practice of the previous calendar year and the respondents were asked to describe their usual or typical management of patients with PAEOC. RESULTS: 45 of 85 CGOs responded (53%). The mean number of ovarian cancer cases operated on by an individual surgeon was 47 (range 6-100). 6% of the surgeons never perform pelvic lymphadenectomy, and 22% of the surgeons never perform para-aortic lymphadenectomy in the primary surgery (PS) group, compared to 8% and 30% in the neoadjuvant chemotherapy (NAC) group. In the PS group 17% of the respondents perform pelvic lymphadenectomy routinely (80% or more of patients) compared to 11% of the respondents in the NAC group. The rates of bowel surgery and surgery for upper abdominal disease were highly variable. The average operating time per case was less than 3h in 78% of the respondents. CONCLUSIONS: The mean operating times, caseload, and types of procedure undertaken in the management of advanced ovarian cancer provide compelling evidence that in many UK cancer centres the surgical goal has not been complete cytoreduction. These data have implications for the centralisation of surgical services, subspecialty training, and the lower survival of UK patients compared to other comparable countries.

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.

Surgical management and follow-up of patients with cervical cancer: survey of gynaecological oncologists in the UK.

We investigated current surgical management and follow-up of women with cervical cancer focusing on treatment of recurrent disease and the use of routine imaging during follow-up among gynaecological oncologists in the UK. A questionnaire including questions regarding perioperative management of primary disease in cervical cancer, follow-up post-treatment, assessment and management of recurrent cervical cancer, was sent to 84 gynaecological oncologists. Some 87% responded. Considerable variations in surgical management and follow-up were identified. With central recurrence of cervical cancer without prior radiotherapy, 90% would recommend radiotherapy instead of an exenteration. For central recurrence in irradiated women, only three (4%) would not recommend an exenteration. In women with pelvic sidewall relapse without prior radiotherapy, 65 responders (96%) would offer radiotherapy, while in pelvic sidewall relapse post-radiation 25 (37%) would recommend pelvic sidewall resection in a specialised centre. A total of 21% used routine imaging during follow-up. The wide variation in clinical practice indicates that there is a need to establish national guidelines for surgical management and follow-up of primary and recurrent cervical cancer.

The role of surgery in patients with advanced gynaecological cancers participating in phase I clinical trials.

OBJECTIVE: While gynaecological cancer patients who participate in Phase I clinical trials are not routinely considered for elective surgery because of a short life expectancy, this should not be overlooked in carefully selected responding patients. METHODS/RESULTS: We describe two cases of patients with different gynaecological cancers, who received treatment within separate phase I trials, and who then proceeded to surgical resection of their cancers, resulting in complete remission. CONCLUSION: Surgery, when feasible, should be taken into consideration as a potential management option, even when patients are receiving treatment within a phase I trial.

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.

Isolated groin recurrence in vulval squamous cell cancer (VSCC). The importance of node count.

OBJECTIVE: To determine whether there is a node count which can define an adequate inguinofemoral lymphadenectomy (IFL) in primary VSCC. METHODS: A retrospective and prospective review of patients with node negative VSCC who had a full staging IFL. Detection of isolated groin recurrences (IGR) would allow groins with higher risk of groin recurrence to be identified. RESULTS: The median node count of 228 IFLs in 139 patients was eight (0-24). There were six IGR (4.3%). Increased rate of IGR was present in patients with increased age, tumour diameter and depth of invasion, lymphovascular space invasion, unilateral IFL, and moderate/poor tumour grade. In the 138 groins with node counts of eight or greater there were no IGRs compared to six in the patients with either undissected groins or groin node counts less than eight (p = 0.030) Interval to IGR was significantly shorter than other sites of recurrence. Both disease-specific and overall survival were significantly reduced in IGR. CONCLUSIONS: An inadequate IFL is a nodal count of less than eight per groin; both these groins and undissected groins are at increased risk of IGR and should have close surveillance.

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.

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.

Early enteral feeding following major abdominal surgery for recurrent gynaecological cancer.

We studied the safety of early postoperative enteral feeding in 22 patients with recurrent gynaecological cancer who underwent major abdominal surgery including extensive adhesiolysis, bowel resection and bowel anastomosis. A total of 19 patients (86.4%) had been treated by both radical surgery and radiation therapy with curative intent. In 18 cases (81.8%), the indication for surgery was bowel obstruction. Preoperative total parenteral nutrition (TPN) was not used. Enteral feeding was given through a gastrostomy tube or a jejunal feeding tube and was commenced within 72 h of completion of surgery. The age range was 30-78 years with a median of 52.8 years. A total of 13 patients (59.1%) had a bowel resection and 17 patients (77.3%) had a bowel anastomosis, all stapled. The median maximum tolerated full strength feeding was 50 ml/h for 18-20 h in a 24 h period and maintained for a median of 9 days. In six patients the feeding was interrupted but was re-commenced in five, in four of whom there was no further interruption of feeding. There were no anastomotic leaks and no cases of aspiration. Postoperative enteral feeding was safe in patients with recurrent gynaecological cancer who had undergone major abdominal surgery and should be considered as an alternative to TPN.

The sentinel lymph node: relevance in gynaecological cancers.

AIMS: Sentinel lymph node (SLN) detection is widely practiced in the management of patients with malignant melanoma and beast cancer. Large studies on SLN detection and determination of nodal status have led to changes in the surgical management of the regional lymph nodes in these diseases. More recently attention has focused on other solid cancers, including gynaecological cancers. METHODS: An extensive literature review of published reports on the SLN in gynaecological cancers was undertaken and the reports were categorised according to the level of evidence provided. RESULTS: Vulva cancer is the most frequently investigated gynaecological cancer with regard to SLN detection because of its anatomical location and easily accessible nodal basin. Although there are no randomised controlled trials, some data suggest SLN detection in vulval cancer may alter clinical practice and reduce the number of groin lymphadenectomies. The lymphatic drainage of the other gynaecological organs is less predictable, the nodal basin less accessible or less well defined, the techniques not standardised and the evidence for the applicability of SLN detection in the management of these cancers is weak. CONCLUSION: Sentinel lymph node detection in vulval cancer may reduce the need for radical groin lymphadenectomy and thereby reduce morbidity. SLN detection for other gynaecological cancers has little potential to alter clinical practice.

Routine computerized tomography scanning, groin ultrasound with or without fine needle aspiration cytology in the surgical management of primary squamous cell carcinoma of the vulva.

We set out to study whether computerized tomography (CT) scanning of the vulva and the groin and groin ultrasound scanning (USS) alone or with fine needle aspiration cytology (FNAC) (USS/FNAC) influenced or could influence the surgical management of primary squamous cell carcinoma of the vulva (SCCaV). Forty-four patients underwent surgery for primary SCCaV following radiologic imaging by one or more modalities. Patient details included the clinical assessment of the carcinoma, radiologic findings, the operation performed, and whether the decision regarding the type and extent of surgery for the vulval carcinoma and, in particular, for the groin node dissection was or could be influenced by the radiologic findings. The age range was 38-87 years, with a median of 74 years. A total of 75 groin dissections were performed. Twenty-five of the 44 patients (56.8%) did not have groin node metastasis, 14 had unilateral metastasis (31.8%), and 5 (11.4%) had bilateral metastasis. All cases with histologically proven nodal status were analyzed to compare the preoperative imaging status with the histology. The calculated sensitivity, specificity, negative predictive value, and positive predictive value for CT were 58%, 75%, 75%, and 58%, for USS alone-87%, 69%, 94%, and 48%, and for USS-guided FNAC-80%, 100%, 93%, and 100%, respectively. There was no patient in whom surgical planning for the vulval carcinoma or the groin nodes was or could be altered by the CT findings. The data do not support the routine use of CT scanning in patients with primary SCCaV, either in assessment of the primary vulval carcinoma or in detecting groin nodal metastases. For the groin nodes, USS/FNAC is superior to CT in assessing disease status. In contrast to CT, USS/FNAC may have a useful clinical role in the management of the groin nodes in vulval carcinoma.

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.