Desiree F. Kolomainen

Epithelial Ovarian Cancer Metastasizing to the Brain: A Late Manifestation of the Disease With an Increasing Incidence

PURPOSE We present the Royal Marsden Hospital experience of cerebral metastases from primary epithelial ovarian carcinoma (EOC) over the last 20 years and examine the evidence for an increasing incidence of EOC metastasizing to this site. PATIENTS AND METHODS A total of 3,690 women with EOC were seen at the Royal Marsden Hospital from 1980 to 2000. Eighteen of these patients developed cerebral metastases. RESULTS Median age at diagnosis of EOC was 52 years (range, 39 to 67). All patients received at least one line of platinum-based chemotherapy; 56% (10 of 18) received more than one line of treatment; 17% (three of 18), two lines; 11% (two of 18), three lines; and 28% (five of 18), four lines. The median treatment interval between each line of chemotherapy was 12, 18, and 4 months. The median interval between diagnosis and CNS relapse was 46 months (range, 12 to 113), in comparison with 5 and 7.5 months for hematogenous relapse in lung or liver, respectively (P <.001). The incidence of CNS metastases in our population from 1980 to 1984 was 0.2%; from 1985 to 1989, 0%; from 1990 to 1994, 0.3%; and from 1995 to 1999, 1.3% (P <.001). An analysis of data from the literature also suggests that the incidence of cerebral metastases from EOC has increased over time. CONCLUSION CNS metastases in EOC are a rare and late manifestation of the disease, occurring in patients with a prolonged survival caused by repeated chemosensitive relapses. An analysis of our data and the data from the literature suggests that the incidence of metastasis at this site in patients with EOC is increasing.

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.

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 of bowel obstruction in gynaecological malignancies

Purpose of reviewBowel obstruction in gynaecological malignancies continues to present clinical challenges and a multidisciplinary approach to discuss management is crucial. Surgery, usually with palliative intent, is associated with significant morbidity and mortality. There is an absence of level 1 evidence and national guidelines, and only limited quality-of-life data. Recent findingsAcute bowel obstruction in gynaecological cancer patients is rare and surgery is associated with a higher morbidity and mortality rate. Less commonly, emergency bowel obstruction cases will have had radiotherapy or recent chemotherapy, which also increases surgical morbidity and mortality. However, most often, bowel obstruction in irradiated gynaecological cancer patients is not due to cancer. Ovarian cancer is the most common malignancy. Caution is needed in those EOC patients with ascites, short treatment-free interval, acute abdomen and chemoresistance. Comorbidities are frequent. The decision for surgery should be made on an individual basis. Palliative care input is important early in patient management as for most patients the surgical goal is palliation and not cure. There is still a paucity of published data on quality-of-life assessments. SummaryThere is a need to identify those patients who may benefit from palliative surgical intervention and those who will not. Ideally, agreed national guidelines should be produced and regularly reviewed.

Venous thromboembolism at time of diagnosis of ovarian cancer: Survival differs in symptomatic and asymptomatic cases

OBJECTIVES To determine the impact on survival of symptomatic and asymptomatic venous thromboembolism (VTE) at time of diagnosis of primary ovarian malignancy. MATERIALS AND METHODS The clinical records of 397 consecutive cases of primary ovarian malignancy were studied. Clinical, pathological and survival data were obtained. RESULTS AND CONCLUSIONS Of 397 cases, 19 (4.8%) were found to have VTE at diagnosis, of which 63.2% (n=12) were asymptomatic. VTE was significantly associated with reduced overall median survival (28 vs. 45 months, p=0.004). Decreased survival was associated with symptomatic VTE compared to patients with asymptomatic VTE (21 vs. 36 months, p=0.02) whose survival was similar to that of patients without VTE. Decreased survival remained significant in symptomatic patients after controlling for stage of disease at diagnosis, cytoreductive status and adjuvant chemotherapy use. Overall these data suggest for the first time that symptomatic but not asymptomatic VTE prior to primary treatment of ovarian cancer is an independent adverse prognostic factor.

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.

Surgical training in gastrointestinal procedures within a UK gynaecological oncology subspecialty programme: Correspondence

roscopically-assisted and robotically-assisted radical hysterectomy in our unit. As highlighted in the accompanying comments in Editor’s choice, there are a number of competing factors that may or actually do undermine subspecialty training, and provide a strong argument for extending the clinical training programme to 3 years. The workforce planning assessment in GO highlights that too many trainees are in post in the UK. The training arrangements in Australia have ensured that the number of Australian trainee fellows matches the needs of the whole country, and that overseas fellows are in post when the demand for local fellows falls. Such a model may need to be adopted in the UK. Newly appointed consultants in GO require close mentoring by senior colleagues during the first 12 months of their consultancy. This mentoring process would replace the formal post-fellowship programme recommended by Naik et al., and would address some of the concerns expressed by Nevin et al. With the new consultant contract, most new appointees will have two or at most three sessions per week for surgery. This is hardly sufficient to maintain let alone develop surgical skills. Our colleagues overseas typically have more operating sessions per week. Counter to current trends, it could be argued (Nevin et al.) that fewer gynaecological oncologists should be performing more surgery, not less. This need not be achieved on an individual practice basis, and although this could be achieved with two consultants operating together on major cases this may not be the best use of resources. Conceivably, certain diseases or problems should be managed on a supra-regional basis. But who decides? How is the balance to be struck between local needs to provide service and national training needs? There are also complex funding issues involved. The surgical community is only just beginning to understand what surgical competency means and how it should be assessed: at present, no surgical examination scrutinises surgical technique, and the assessments made by the trainers are solely relied upon. It is clear that a subspecialty training programme in GO must provide a high volume of surgical cases, and provide experience in surgical management of complex primary and recurrent disease. Selfevidently not all UK programmes do this. Perhaps training programmes should be amalgamated to achieve training goals, and to maintain and improve standards. There is no formal examination in GO and no specific GO-related appraisal/revalidation is carried out in the UK, in contrast to North America, where both are compulsory. If GO is to survive as a subspecialty then the core strength will be comprehensive surgical training in approved centres. Two-year programmes do not, we believe, provide this level of training. The issues raised by Naik et al. and Nevin et al. are relevant to all GO trainers and trainees alike. Their solution rests with stakeholders such as the British Gynaecological Cancer Society (BGCS) and the Royal College of Obstetricians and Gynaecologists (RCOG), but most importantly with the GO surgical community. Maintaining the status quo of too many training centres and too many trainees will ultimately undermine the very basis of subspecialty training. j

Hormone replacement therapy following breast and gynaecological cancer

he use of hormone replacement therapy (HRT) remains an area of much debate and controversy. T HRT is prescribed both for the short-term relief of menopausal symptoms and in the longer term because of health benefits related, in the main, to cardiovascular disease and the prevention of osteoporosis. There is also the perception of an improved quality of life. Most women will experience symptoms to some degree at the menopause, whether it occurs naturally or following treatment for benign or malignant disease. These symptoms may persist for five years or more in up to 20% of women. They include hot flushes, night sweats and insomnia, lethargy, irritability, loss of concentration, depression, vaginal dryness, dyspareunia, dysuria and joint problems. The benefits and efficacy of oestrogen replacement in relieving these distressing symptoms are well recognised and no proven, effective alternatives exist. In the longer term, good evidence exists to support claims of reductions in morbidity and mortality due to cardiovascular disease’J and o s t e o p o r ~ s i s ~ ~ ~ with HRT. Concerns have arisen, however, about the possible adverse effects of HKT, particularly with respect to increased risks of breast cancer4 and thromboembolic disease. The siluation is further complicated in women who have received treatment for a gynaecological malignancy, since hormonal factors are undoubtedly o f importance in the aetiology of some gynaecological cancers. It is not unreasonable to assume that the prescription of HRT to women following treatment for gynaecological malignancy could adversely affect their prognosis and increase the chances of recurrent disease. Many women suffering from gynaecological cancers experience premature menopause induced by treatment with surgery, chemotherapy or radiotherapy. As a result of the concerns alluded to above, doctors have traditionally Jonathan Herod MB ChB MRCOG

The Use of Laparostomy in Patients With Gynecologic Cancer First Report From a UK Cancer Center

Objective To report on the use of laparostomy after major gynecologic cancer surgery. Methods Operative records and surgical databases of patients who underwent major open abdominal surgery over a 6.5-year period at a tertiary referral center were searched. Patients who had diagnostic procedures, operative laparoscopy, and surgery for vulval cancer were excluded. All patients who had laparostomy were identified; and the diagnosis, indication for laparostomy, method of temporary cover, and complications were recorded. Results A total of 1592 laparotomies, including 37 emergencies, were performed. Of these, 14 patients (0.88%) had a laparostomy. Seven patients had primary cancer and 7 had recurrent cancer. As more patients had surgery for primary disease, laparostomy was more common in patients who underwent surgery for recurrent cancer. Seven patients had ovarian/fallopian tube/primary peritoneal cancer, 4 patients had uterine cancer, 2 patients had cervical cancer, and one patient had vaginal cancer. Ten laparostomies (71.4%) were performed after an emergency procedure; thus, laparostomy was approximately 100 times more common after emergency than elective major surgery. Massive bowel distension and bowel wall edema were the major indications for laparostomy. The method of temporary closure was variable, and a sterile saline bag was the most commonly used. The laparostomy was closed in all but 2 patients, most often on postoperative day 2 or 3. Two patients (14.3%) died within 30 days of the laparostomy, and 2 others died at postoperative days 40 and 62. Three of these 4 patients had recurrent cancer, and 2 patients had emergency procedures. Conclusions The overall incidence of laparostomy associated with laparotomy for gynecological cancer surgery was less than 1:100 cases, was more common after surgery for recurrent cancer, and in particular, was approximately 100 times more common after emergency procedures. The 30-day operative mortality rate was 14.3%.

Para-aortic lymphadenectomy in endometrial cancer.

Yukiharu Todo and colleagues’ thought-provoking paper (April 3, p 1165) addresses an important and much debated area in the practice of gynaecological oncology. The retrospective study was over a long period of time during which there have been many changes both in the staging and management of endo metrial cancer. Todo and colleagues do not state whether imaging formed part of their preoperative work-up nor whether the pelvic and para-aortic nodes were known to be involved preoperatively. Currently, MRI is often used for preoperative staging and patients identifi ed as low risk on the basis of histology and imaging would not under go a staging lymphadenectomy. It would have been informative to know the incidence of pelvic and paraaortic metastasis separately in the intervention group, especially since chemotherapy has been shown to improve survival. Pelvic and para-aortic lymphadenectomy has been shown to be an independent prognostic factor for overall survival; it is, however, important that data for surgical morbidity be included as well. It should also be noted that there was a striking diff erence in the adjuvant treatment policy between the two centres. With the current trend towards minimum access surgery, would Todo and colleagues consider incorporating this into their clinical practice?