British Gynaecological Cancer Society (BGCS) cervical cancer guidelines: Recommendations for practice.

Cervix cancer in many countries is declining and screening programmes and immunisation will reduce the incidence in the next few decades. This guideline attempts to cover management of invasive disease reflecting diagnosis and imaging including new imaging and sentinel lymph node biopsies. Smaller volume disease is usually managed surgically whereas advanced disease is treated with (chemo)- radiation. It also includes discussion of fertility sparing procedures. Practices are changing frequently for all aspects of care usually in attempts to reduce complications and improve quality of life. The management of advanced disease is treated by chemotherapy and the use of newer agents is also discussed. Other sections discuss specialist situations such as cancer in pregnancy, rare cervical tumours, late effects and supportive measures and fertility preserving approaches.

The Impact of Sociodemographic Factors and Emergency Admissions on the Place of Death of Gynecological Cancer Patients in England: An Analysis of a National Mortality-Hospital Episode Statistics-Linked Data Set.

OBJECTIVE: The aim of this study was to develop a predictive model for risk of death in hospital for gynecological cancer patients specifically examining the impact of sociodemographic factors and emergency admissions to inform patient choice in place of death. METHODS: The model was based on data from 71,269 women with gynecological cancer as underlying cause of death in England, January 1, 2000, to July 1, 2012, in a national Hospital Episode Statistics-Office for National Statistics database. Two thousand eight hundred eight deaths were used for validation of the model. Logistic regression identified independent predictors of a hospital death: adjusting for year of death, age group, income deprivation quintile, Strategic Health Authority, gynecological cancer site, and number of elective and emergency hospital admissions and respective total durations of stay. RESULTS: Forty-three percent of deaths from gynecological cancer occurred in hospital. The variables significantly predicting death in hospital were less recent year of death (odds ratio [OR], 0.93; P < 0.001), increasing age (OR, 1.17; P < 0.001), increasing deprivation (OR, 1.06; P < 0. 001), increasing frequency and length of elective and emergency admissions (P < 0.001). The model correctly identified 73% of hospital deaths with a sensitivity of 75% and a specificity of 72%. The areas under the receiver operating curve were 0.78 for the predictive model and 0.71 for the validation data set. Each subsequent emergency admission in the last month of life increased the odds of death in hospital by 2.4 times (OR, 2.38; P < 0.001). Hospital deaths were significantly lower in all other regions compared with London. The model predicted a 16% reduction of deaths in hospital if 50% of emergency hospital admissions in the last month of life could be avoided by better community care. CONCLUSIONS: Our findings could enable identification of patients at risk of dying in hospital to ensure greater patient choice for place of death.

Medical and surgical interventions for the treatment of usual-type vulval intraepithelial neoplasia.

BACKGROUND: Usual-type vulval intraepithelial neoplasia (uVIN) is a pre-cancerous condition of the vulval skin. Also known as high-grade VIN, VIN 2/3 or high-grade vulval squamous intraepithelial lesion (HSIL), uVIN is associated with high-risk subtype human papilloma virus (HPV) infection. The condition causes distressing vulval symptoms in the majority of affected women and may progress to vulval cancer, therefore is usually actively managed. There is no consensus on the optimal management of uVIN. High morbidity and recurrence rates associated with surgical treatments make less invasive treatments highly desirable. OBJECTIVES: To determine which interventions are the most effective, safe and tolerable for treating women with uVIN. SEARCH METHODS: We searched the Cochrane Gynaecological Cancer Group Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL), Issue 8 2015, MEDLINE and EMBASE (up to 1 September 2015). We also searched registers of clinical trials, abstracts of scientific meetings, reference lists of included studies and contacted experts in the field. SELECTION CRITERIA: Randomised controlled trials (RCTs) that assessed medical and surgical interventions in women with uVIN. If no RCTs were available, we included non-randomised studies (NRSs) with concurrent comparison groups that controlled for baseline case mix in multivariate analysis. DATA COLLECTION AND ANALYSIS: We used Cochrane methodology with two review authors independently extracting data and assessing risk of bias. Where possible, we synthesised data in meta-analyses using random-effects methods. Network meta-analysis was not possible due to insufficient data. MAIN RESULTS: We included six RCTs involving 327 women and five NRSs involving 648 women. The condition was variously named by investigators as uVIN, VIN2/3 or high-grade VIN. Five RCTs evaluated medical treatments (imiquimod, cidofovir, indole-3 carbinol), and six studies (one RCT and five NRSs) evaluated surgical treatments or photodynamic therapy. We judged two RCTs and four NRSs to be at a high or unclear risk of bias; we considered the others at relatively low risk of bias. Types of outcome measures reported in NRSs varied and we were unable to pool NRS data. Medical interventions: Topical imiquimod was more effective than placebo in achieving a response (complete or partial) to treatment at five to six months post-randomisation (three RCTs, 104 women; risk ratio (RR) 11.95, 95% confidence interval (CI) 3.21 to 44.51; high-quality evidence). At five to six months, a complete response occurred in 36/62 (58%) and 0/42 (0%) women in the imiquimod and placebo groups, respectively (RR 14.40, 95% CI 2.97 to 69.80). Moderate-quality evidence suggested that the complete response was sustained at one year (one RCT, nine complete responses out of 52 women (38%)) and beyond, particularly in women with smaller VIN lesions. Histologically confirmed complete response rates with imiquimod versus cidofovir at six months were 45% (41/91) and 46% (41/89), respectively (one RCT, 180 women; RR 1.00, 95% CI 0.73 to 1.37; moderate-quality evidence). Twelve-month data from this trial are awaited; however, interim findings suggested that complete responses were sustained at 12 months. Only one trial reported vulval cancer at one year (1/24 and 2/23 in imiquimod and placebo groups, respectively). Adverse events were more common with imiquimod than placebo and dose reductions occurred more frequently in the imiquimod group than in the placebo group (two RCTs, 83 women; RR 7.77, 95% CI 1.61 to 37.36; high-quality evidence). Headache, fatigue and discontinuation were slightly more common with imiquimod than cidofovir (moderate-quality evidence). Quality of life scores reported in one trial (52 women) were not significantly different for imiquimod and placebo. The evidence of effectiveness of topical treatments in immunosuppressed women was scant. There was insufficient evidence on other medical interventions. Surgical and other interventions: Low-quality evidence from the best included NRS indicated, when data were adjusted for confounders, that there was little difference in the risk of VIN recurrence between surgical excision and laser vaporisation. Recurrence occurred in 51% (37/70) of women overall, at a median of 14 months, and was more common in multifocal than unifocal lesions (66% versus 34%). Vulval cancer occurred in 11 women (15.1%) overall at a median of 71.5 months (9 to 259 months). The risk of vulval cancer did not differ significantly between excision and laser vaporisation in any of the NRSs; however, events were too few for robust findings. Alternative surgical procedures that might be as effective include Cavitron ultrasonic surgical aspiration (CUSA) and loop electrosurgical excision (LEEP) procedures, based on low- to very low-quality evidence, respectively. Very low-quality evidence also suggested that photodynamic therapy may be a useful treatment option.We found one ongoing RCT of medical treatment (imiquimod) compared with surgical treatment. AUTHORS' CONCLUSIONS: Topical treatment (imiquimod or cidofovir) may effectively treat about half of uVIN cases after a 16-week course of treatment, but the evidence on whether this effect is sustained is limited. Factors predicting response to treatment are not clear, but small lesions may be more likely to respond. The relative risk of progression to vulval cancer is uncertain. However, imiquimod and cidofovir appear to be relatively well tolerated and may be favoured by some women over primary surgical treatment.There is currently no evidence on how medical treatment compares with surgical treatment. Women who undergo surgical treatment for uVIN have about a 50% chance of the condition recurring one year later, irrespective of whether treatment is by surgical excision or laser vaporisation. Multifocal uVIN lesions are at a higher risk of recurrence and progression, and pose greater therapeutic dilemmas than unifocal lesions. If occult cancer is suspected despite a biopsy diagnosis of uVIN, surgical excision remains the treatment of choice. If occult cancer is not a concern, treatment needs to be individualised to take into account the site and extent of disease, and a woman's preferences. Combined modalities may hold the key to optimal treatment of this complex disease.

Medical interventions for high-grade vulval intraepithelial neoplasia.

BACKGROUND: This is an updated version of a review first published in theCochrane Database of Systematic Reviews, Issue 4, in 2011. Vulval intraepithelial neoplasia (VIN) is a pre-cancerous condition of the vulval skin and its incidence is increasing in women under 50 years. High-grade VIN (also called usual-type VIN (uVIN) or VIN 2/3 or high-grade vulval intraepithelial lesion) is associated with human papilloma virus (HPV) infection and may progress to vulval cancer, therefore is usually actively managed. There is no consensus on the optimal management of high-grade VIN; and the high morbidity and relapse rates associated with surgical interventions make less invasive interventions highly desirable. OBJECTIVES: To evaluate the effectiveness and safety of medical (non-surgical) interventions for high-grade VIN. SEARCH METHODS: We searched the Cochrane Gynaecological Cancer Group Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2015, Issue 3), MEDLINE and EMBASE (up to 30 March 2015). We also searched registers of clinical trials, abstracts of scientific meetings, reference lists of included studies and contacted experts in the field. SELECTION CRITERIA: Randomised controlled trials (RCTs) that assessed non-surgical interventions in women diagnosed with high-grade VIN. DATA COLLECTION AND ANALYSIS: We used Cochrane methodology with two review authors independently abstracting data and assessing risk of bias. Where possible, we synthesised data in meta-analyses using random effects methods. MAIN RESULTS: Five trials involving 297 women with high-grade VIN (defined by trial investigators as VIN 2/3 or VIN 3 or 'high-grade' lesions) met our inclusion criteria: three trials assessed the effectiveness of topical imiquimod versus placebo; one assessed topical cidofovir versus topical imiquimod; and one assessed low- versus high-dose indole-3-carbinol in similar types of participants. Three trials were at a moderate to low risk of bias, two were at a potentially high risk of bias.Meta-analysis of the three trials comparing topical imiquimod 5% cream to placebo found that women in the active treatment group were more likely to show an overall response (complete and partial response) to treatment at five to six months compared with the placebo group (Risk Ratio (RR) 11.95, 95% confidence interval (CI) 3.21 to 44.51; participants = 104; studies = 3; I(2) = 0%; high-quality evidence). A complete response at five to six months occurred in 36/62 (58%) and 0/42 (0%) participants in the active and placebo groups, respectively (RR 14.40, 95% CI 2.97 to 69.80; participants = 104; studies = 3; I(2) = 0%). A single trial reported 12-month follow-up, which revealed a sustained effect in overall response in favour of the active treatment arm at 12 months (RR 9.10, 95% CI 2.38 to 34.77; moderate-quality evidence), with 9/24 (38%) and 0/23 (0%) complete responses recorded in the active and placebo groups respectively. Progression to vulval cancer was also documented in this trial (one versus two participants in the active and placebo groups, respectively) and we assessed this evidence as low-quality. Only one trial reported adverse events, including erythema, erosion, pain and pruritis at the site of the lesion, which were more common in the imiquimod group. Dose reductions occurred more frequently in the active treatment group compared with the placebo group (19/47 versus 1/36 participants; RR 7.77, 95% CI 1.61 to 37.36; participants = 83; studies = 2; I(2) = 0%; high-quality evidence). Only one trial reported quality of life (QoL) and there were no significant differences between the imiquimod and placebo groups.For the imiquimod versus cidofovir trial, 180 women contributed data. The overall response at six months was similar for the imiquimod and cidofovir treatment groups with 52/91 (57%) versus 55/89 (62%) participants responding, respectively (RR 0.92, 95% CI 0.73 to 1.18). A complete response occurred in 41 women in each group (45% and 46%, respectively; RR 1.00, 95% CI 0.73 to 1.37). Although not statistically different, total adverse events were slightly more common in the imiquimod group of this trial with slightly more discontinuations occurring in this group. Longer term response data from this trial are expected.The small trial comparing two doses of indole-3-carbinol contributed limited data. We identified five ongoing randomised trials of various interventions for VIN. AUTHORS' CONCLUSIONS: Topical imiquimod appears to be a safe and effective treatment for high-grade VIN (uVIN), even though local side-effects may necessitate dose reductions. However, longer term follow-up data are needed to corroborate the limited evidence that response to treatment is sustained, and to assess any effect on progression to vulval cancer. Available evidence suggests that topical cidofovir may be a good alternative to imiquimod; however, more evidence is needed, particularly regarding the relative effectiveness on longer term response and progression. We await the longer-term response data and the results of the five ongoing trials.

Surgical interventions for high-grade vulval intraepithelial neoplasia.

BACKGROUND: This is an updated version of an original Cochrane review published in The Cochrane Library, 2011, Issue 1.Vulval intraepithelial neoplasia (VIN) is a pre-malignant condition of the vulval skin. This uncommon chronic skin condition of the vulva is associated with a high risk of recurrence and the potential to progress to vulval cancer. The condition is complicated by its multicentric and multifocal nature. The incidence of this condition appears to be rising, particularly in the younger age group. There is a lack of consensus on the optimal surgical treatment method. However, the rationale for the surgical treatment of VIN has been to treat the symptoms and exclude any underlying malignancy, with the continued aim of preserving the vulval anatomy and function. Repeated treatments affect local cosmesis and cause psychosexual morbidity, thus impacting he individual's quality of life. OBJECTIVES: To evaluate the effectiveness and safety of surgical interventions in women with high-grade VIN. SEARCH METHODS: We searched the Cochrane Gynaecological Cancer Group Trials Register and the Cochrane Central Register of Controlled Trials (CENTRAL) Issue 11,2013 and MEDLINE and EMBASE up to December 2013. We also searched registers of clinical trials, abstracts of scientific meetings and reference lists of included studies, and contacted experts in the field. SELECTION CRITERIA: Randomised controlled trials (RCTs) that compared surgical interventions in adult women diagnosed with high-grade VIN. DATA COLLECTION AND ANALYSIS: Two review authors independently abstracted data and assessed risk of bias. MAIN RESULTS: We identified one RCT, including 30 women, that met our inclusion criteria; this trial reported data on carbon dioxide (CO2) laser surgery versus cavitational ultrasonic surgical aspiration (CUSA). There were no statistically significant differences in the risks of disease recurrence after one year of follow-up, pain, scarring, dysuria or burning, adhesions, infection, abnormal discharge or eschar between women who underwent CO2 laser surgery and those who received CUSA. The trial lacked statistical power due to the small number of women in each group and the low number of observed events, but was at low risk of bias. AUTHORS' CONCLUSIONS: The included trial lacked statistical power due to the small number of women in each group and the low number of observed events. The absence of reliable evidence regarding the effectiveness and safety of the two surgical techniques for the management of VIN therefore precludes any definitive guidance or recommendations for clinical practice.

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%.

A detailed immunohistochemical analysis of 2 cases of papillary cystadenoma of the broad ligament: an extremely rare neoplasm characteristic of patients with von hippel-lindau disease.

We report 2 cases of papillary cystadenoma, a rare neoplasm characteristic of patients with Von Hippel-Lindau (VHL) disease, involving the pelvic soft tissues of women and probably arising within the broad ligament. In only one of the women was there a history of VHL disease. The other woman was investigated for VHL disease after the diagnosis of papillary cystadenoma and all tests were negative. There has been debate as to whether papillary cystadenomas in women are of mesonephric (Wolffian) or of Mullerian origin and to investigate this we undertook a detailed immunohistochemical analysis. Both tumors were positive with AE1/3, Ber EP4, epithelial membrane antigen, CK7, CD10, CA125, CA19.9, calretinin, and vimentin. One exhibited focal nuclear staining with WT1 and PAX8. The tumors were negative with estrogen receptor, progesterone receptor, androgen receptor, CK20, CEA, TTF1, inhibin, RCC marker, and hepatocyte nuclear factor 1ß. Although favoring a mesonephric origin, the immunohistochemical findings are essentially inconclusive and not definitive for either a mesonephric or a Mullerian origin. We believe that patients found to have papillary cystadenoma should be investigated for VHL disease if there is no history of this. This is the second reported example of papillary cystadenoma in a woman not known to have VHL disease and the first in which investigations have excluded this disease.

Medical interventions for high grade vulval intraepithelial neoplasia.

BACKGROUND: Vulval intraepithelial neoplasia (VIN) is a pre-malignant condition of the vulval skin; its incidence is increasing in women under 50 years. VIN is graded histologically as low grade or high grade. High grade VIN is associated with infection with human papilloma virus (HPV) infection and may progress to invasive disease. There is no consensus on the optimal management of high grade VIN. The high morbidity and high relapse rate associated with surgical interventions call for a formal appraisal of the evidence available for less invasive but effective interventions for high grade VIN. OBJECTIVES: To evaluate the effectiveness and safety of medical interventions for high grade VIN. SEARCH STRATEGY: We searched the Cochrane Gynaecological Cancer Group Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2010, Issue 3), MEDLINE and EMBASE (up to September 2010). We also searched registers of clinical trials, abstracts of scientific meetings, reference lists of included studies and contacted experts in the field. SELECTION CRITERIA: Randomised controlled trials (RCTs) that assessed medical interventions, in adult women diagnosed with high grade VIN. DATA COLLECTION AND ANALYSIS: Two review authors independently abstracted data and assessed risk of bias. Where possible the data were synthesised in a meta-analysis. MAIN RESULTS: Four trials met our inclusion criteria: three assessed the effectiveness of topical imiquimod versus placebo in women with high grade VIN; one examined low versus high dose indole-3-carbinol in similar women. Meta-analysis of three trials found that the proportion of women who responded to treatment at 5 to 6 months was much higher in the group who received topical imiquimod than in the group who received placebo (relative risk (RR) = 11.95, 95% confidence interval (CI) 3.21 to 44.51). A single trial showed similar results at 12 months in (RR = 9.10, 95% CI 2.38 to 34.77). Only one  trial reported adverse events, which were more common in the imiquimod group. One trial found no significant differences in quality of life (QoL) or body image between the imiquimod and placebo groups. AUTHORS' CONCLUSIONS: Imiquimod appears to be effective, but its safety needs further examination. Its use is associated with side effects which are tolerable, but more extensive data on adverse effects are required. Long term follow-up should be mandatory in view of the known progression of high grade VIN to invasive disease. Alternative medical interventions, such as cidofovir, should be explored.

Surgical interventions for high grade vulval intraepithelial neoplasia.

BACKGROUND: Vulval intraepithelial neoplasia (VIN) is a pre-malignant condition of the vulval skin. This uncommon chronic skin condition of the vulva is associated with a high risk of recurrence and the potential to progress to vulval cancer. The condition is complicated by its' multicentric and multifocal nature. The incidence of this condition appears to be rising particularly in the younger age group.There is a lack of consensus on the optimal surgical treatment method. However, the rationale for surgical treatment of VIN has been to treat symptoms and exclude underlying malignancy with the continued aim of preservation of vulval anatomy and function. Repeated treatments affect local cosmesis and cause psychosexual morbidity thus impacting on the patients' quality of life. OBJECTIVES: To evaluate the effectiveness and safety of surgical interventions for high grade VIN. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), Issue 3, 2010, Cochrane Gynaecological Cancer Group Trials Register, MEDLINE and EMBASE up to September 2010. We also searched registers of clinical trials, abstracts of scientific meetings, reference lists of included studies and contacted experts in the field. SELECTION CRITERIA: Randomised controlled trials (RCTs) that compared surgical interventions, in adult women diagnosed with high grade vulval intraepithelial neoplasia. DATA COLLECTION AND ANALYSIS: Two review authors independently abstracted data and assessed risk of bias. MAIN RESULTS: We found only one RCT which included 30 women that met our inclusion criteria and this trial reported data on carbon dioxide laser (CO(2) laser) versus ultrasonic surgical aspiration (USA).There was no statistically significant difference in the risk of disease recurrence after one year follow-up, pain, presence of scarring, dysuria or burning, adhesions, infection, abnormal discharge and eschar between women who received CO(2) laser and those who received USA. The trial lacked statistical power due to the small number of women in each group and the low number of observed events, but was at low risk of bias. AUTHORS' CONCLUSIONS: The included trial lacked statistical power due to the small number of women in each group and the low number of observed events. Therefore in the absence of reliable evidence regarding the effectiveness and safety of the two surgical techniques for the management of vulval intraepithelial neoplasia precludes any definitive guidance or recommendations for clinical practice.