Sinecatechins ointment as a potential novel treatment for usual type vulval intraepithelial neoplasia: a single-centre double-blind randomised control study.

OBJECTIVE: To compare the safety and efficacy of 10% sinecatechins (Veregen® ) ointment against placebo in the treatment of usual type vulvar intraepithelial neoplasia (uVIN). DESIGN: A Phase II double-blind randomised control trial. SETTING: A tertiary gynaecological oncology referral centre. POPULATION: All women diagnosed with primary and recurrent uVIN. METHODS: Eligible patients were randomised 1:1 to receive either sinecatechins or placebo ointment (applied three times daily for 16 weeks) and were followed up at 2, 4, 8, 16, 32 and 52 weeks. MAIN OUTCOME MEASURES: The primary outcome measure, recorded at 16 and 32 weeks, was histological response (HR). Secondary outcome measures included clinical (CR) response, toxicity, quality of life and pain scores. RESULTS: There was no observed difference in HR between the two arms. However, of the 26 patients who were randomised, all 13 patients who received sinecatechins showed either complete (n = 5) or partial (n = 8) CR, when best CR was evaluated. In placebo group, three patients had complete CR, two had partial CR, six had stable disease and two were lost to follow up. Patients in the sinecatechins group showed a statistically significant improvement in best observed CR as compared with the placebo group (P = 0.002). There was no difference in toxicity reported in either group. CONCLUSION: Although we did not observe a difference in HR between the two treatment arms, we found that 10% sinecatechins application is safe and shows promise in inducing clinical resolution of uVIN lesions and symptom improvement, thus warranting further investigation in a larger multicentre study. TWEETABLE ABSTRACT: A randomised control study indicating that sinecatechins ointment may be a novel treatment for uVIN.

Current insights into the aetiology, pathobiology, and management of local disease recurrence in squamous cell carcinoma of the vulva.

Squamous cell carcinoma of the vulva is predominantly a disease of the elderly, where the mainstay of treatment is radical surgery. Local vulval recurrence (LVR) is a significant problem for these patients, and the rates of recurrence have not improved over the last three decades. Disappointingly, we still lack an understanding of how LVRs develop, and the best approach to prevent and manage the condition. This review discusses recent insights into the key prognostic factors that influence the risk of recurrence, focusing on the role of tumour-adjacent non-neoplastic epithelial disorders, which are thought to play a causative role. TWEETABLE ABSTRACT: A review that discusses the key prognostic factors that influence local recurrence in vulval cancer.

Adjacent Lichen Sclerosis predicts local recurrence and second field tumour in women with vulvar squamous cell carcinoma.

OBJECTIVE: In this study, we investigated if the presence of histologically abnormal epithelium adjacent to the primary tumour influenced the frequency, timing, and topography of local vulvar recurrences (LVR) following treatment for squamous cell carcinoma of the vulva (VSCC). METHODS: The study population comprised a cohort of 201 consecutive cases with incident VSCC. LVR were categorised as local relapses (LR) if they occurred <2cm from the tumour margins, and as second field tumours (SFT) when ≥2cm from these margins. Univariable and multivariable competing risk modelling was performed to identify the prognostic factors associated with local disease recurrence. RESULTS: The characterization of the epithelium adjacent to the invasive component was possible for 199 (99.0%) patients. Of these, 171 (85.9%) were found to have intraepithelial abnormalities found adjacent to the surgical specimen. Multivariable analyses revealed that, following adjustment, Lichen Sclerosis (LS) was associated with an increase in the incidence of LVR, LR and SFT (SHRs: 3.4, 2.7 and 4.4, respectively). Although the incidence of LR and SFT in women with LS associated VSCC was similar, the peak incidence of SFT occurred more than two years before that of LR. CONCLUSIONS: Women with VSCC arising in a field of LS may continue to have an increased risk of developing LR and SFT for many years after resection of their primary tumour. Our study suggests that these women should be followed up more regularly so that LVR can be detected earlier; unless a more robust surveillance programme or chemopreventative treatments become available.

The role of regional anaesthesia in the surgical management of vulval malignancy.

Abstract Surgical excision is the management of choice in vulval cancer however, the patient population are typically elderly and comorbid, for whom general anaesthesia (GA) carries considerable risk. The outcome of 107 procedures were reviewed in order investigate the postoperative complication rates associated with general and regional anaesthesia for the surgical management of vulval cancer. GA was used in 78 (72.9%) cases; 27 (22.9%) had a regional anaesthetic (spinal/epidural/ileoinguinal) and two women had a GA following a failed spinal anaesthetic. Women having a regional anaesthetic were significantly older (p = 0.0198), had a higher ACE (p = 0.0001) and ASA score (p < 0.0001) than those having a GA. There was an association between GA and grade II+ complications, compared with regional techniques (odds ratio, OR 2.72) but this was not significant due to the small number of events. Regional anaesthetic techniques are safe, well-tolerated alternatives to GA for the surgical management of vulval cancer, especially in an elderly and comorbid population.

The use of sentinel node sampling in vulval cancer.

Between March 2007 and December 2009, 38 patients underwent sentinel lymph node biopsy (SLNB) sampling, along with vulvectomy, in their management of vulval cancer. A review has been conducted to establish the reliability and accuracy of the new procedure compared with the traditional total inguinofemoral lymphadenectomy. We also aimed to establish both the short- and long-term morbidities of both total inguinofemoral lymphadenectomy and SLNB and to assess the duration of hospital stay in both groups. Our data have shown a reduced short- and long-term morbidity and reduced length of hospital stay for the SLNB procedure. We conclude that it is a reliable and safe procedure, however it should only be conducted in cancer centres.

Impact of improving outcome guidance in gynaecological cancer on squamous cell carcinoma of the vulva in the West Midlands, UK.

This study aimed to assess the benefits and outcomes of squamous cell carcinoma (SCC) of the vulva managed in a cancer centre post-centralisation of cancer care in the UK. A retrospective study was performed to evaluate the demography and management outcomes of SCC of the vulva in a regional gynaecological cancer centre. The results were then compared with the Rhodes et al. (1998) population-based study. Over the years, disease demography remained largely unchanged. However, centralisation of cancer care has resulted in significant changes in the pattern of care. The number of cases managed has increased by 1.7 times and the permutation of surgeries have reduced from 15 to 4. There is also a significant increased in the number of lymphadenectomies performed (p = 0.003). These changes were accompanied by improvement in 5-year cause-specific survival (p = 0.055).

The angiome: a new concept in cancer biology.

Angiogenesis is a key process in cancer biology, and justifies focus on the endothelium. Separate studies have looked at different aspects of angiogenesis and vascular biology, primarily focusing on certain laboratory and imaging techniques that generally reflect one particular aspect of the assessment of the endothelium. These techniques include the secretion/release of molecules (such as growth factors) into the plasma, by the presence of mature and progenitor endothelial cells themselves in the circulation, but also by examination of peripheral blood flow and the local circulation of the tumour, and cells of the tumour itself. However, a limitation of this approach is that these methods, although themselves being useful, have often been viewed in isolation and thus can provide only a part of the vascular picture. The authors submit that this approach is weak, and introduce 'the angiome' as a term which fuses several different aspects of endothelial and tumour biology into a single concept. The authors suggest that the adoption of the concept of the angiome will bring improved insights into angiogenesis and thus cancer cell biology. In justifying this concept, the authors review the current understanding of endothelial biology and the methods of its assessment, and hypothesise that a more multifactorial approach to the angiome will be a crucial determinant of outcomes of and treatment strategies for diseases, in particular antiangiogenics for cancer therapy.

Long-term follow-up of cervical disease in women screened by cytology and HPV testing: results from the HART study.

BACKGROUND: Several studies have shown that testing for high-risk human papillomavirus (HPV) types results in an improved sensitivity for CIN2+, compared with cytology, although with a somewhat lower specificity. METHODS: We obtained follow-up results, with at least one smear after participation in the HART study, which compared HPV testing (HC-II) with cytology as a primary screening modality. RESULTS: With a median follow-up of 6 years, 42 additional cases of CIN2+ were identified; women who were HPV positive at baseline were more likely to develop CIN2+ than those who were HPV negative (hazard ratio (HR) 17.2; 95% confidence interval (CI) (9.3-31.6)) and the risk increased with increasing viral load. Compared with HPV-negative women (relative light unit (RLU) <1), the HR (95% CI) was 5.4 (1.6, 18.2) for 1-10 RLU and 25.5 (13.6, 47.9) for RLU > or = 10. Positive cytology (borderline or worse compared with negative) was also predictive of developing CIN2, although to a lesser extent (HR 8.7; 95% CI (4.5-17.1)). Only one case of CIN3 and three cases of CIN2 were found in women who showed a positive cytology result but were HPV negative at baseline. CONCLUSION: After 5 years of follow-up, CIN2+ occurred in 0.23% of women who were HPV negative at baseline compared with 0.48% of women who showed a negative cytology result, indicating a much longer low-risk interval for CIN2+ after HPV testing.

Anaesthetic choice in the colposcopy clinic: a retrospective analysis of routinely collected data.

OBJECTIVES: Current guidelines recommend that less than 20% of treatments in colposcopy clinics should be under general anaesthetic. The objective of this study was to increase the evidence base for guidelines by establishing the proportion of women receiving general anaesthesia for treatment, determining the predictors of and reasons recorded for general anaesthetic use. DESIGN: Retrospective analysis of routinely collected data. SETTING: NHS Trust in the West Midlands. PARTICIPANTS: Colposcopy patients; January 2003 to March 2005. METHODS: Logistic regression of factors associated with general anaesthetic choice. MAIN OUTCOME MEASURES: Proportion of women treated under general anaesthesia, factors associated with anaesthetic choice and reasons recorded for general anaesthetic use. RESULTS: About 5.4% (204/3777) of new appointments for colposcopy received treatment under general anaesthetic. Of women requiring treatment, 20% (204/1003) received general anaesthetic. General anaesthetic was more likely to be used when the woman required loop excision (OR = 3.63, 95% CI 2.11-6.24) and less likely when directed biopsy was performed (OR = 0.11, 95% CI 0.01-0.80), when the patient appointment date was after introduction of new guidelines (OR = 0.37, 95% CI 0.24-0.56) or when the assessment visit was with a nonconsultant status doctor rather than nurse or consultant (OR = 0.70, 95% CI 0.50-0.97). General anaesthetic use varied between colposcopists ranging from 0 to 16.5% of new patients seen. Woman's choice was the most commonly specified reason for the use of general anaesthetic. CONCLUSIONS: The proportion of colposcopy patients treated under general anaesthetic is 20%, within guideline limits. Substantial variation in general anaesthetic rates between colposcopists was observed, and further investigation is required to discover the reason for this.

Identifying the performance criteria for appraisal of colposcopists: benchmarking Delphi.

BACKGROUND: Colposcopy forms an essential part of National Health Service Cervical Screening Programme (NHSCSP). With an increased emphasis on accountability and improved performance, there is a need to identify the performance criteria that are essential to be satisfied by the colposcopists at the time of appraisal. OBJECTIVE: To identify the performance criteria essential for appraisal of colposcopists by two-generational Delphi survey. DESIGN: Delphi survey. SETTING: Annual British Society for Colposcopy and Cervical Pathology conference (BSCCP 2005, Edinburgh, UK). POPULATION: Four hundred and ninety-nine delegates attending the above conference. METHOD: A two-generational Delphi survey was undertaken to identify the criteria needed for appraisal. The participants were asked to rate the relevance of quality items that might be considered necessary for appraisal of performance of colposcopists. After the first round, the results were presented, and the respondents were given the chance to reflect on their response and change it if necessary. MAIN OUTCOME MEASURES: Criteria considered to be essential for appraisal of colposcopists in areas of training, diagnostic and therapeutic aspects and communication. RESULTS: In the first round, 306/499 (61%) participants returned the completed questionnaire. Sixty percent (187/306) of participants returned their questionnaire in the second round. In addition to BSCCP certification, four other criteria were identified, which were quality of recorded findings, biopsy rate when atypia noted, proportion of biopsies histologically adequate and proportion of normal initial posttreatment follow-up smears. CONCLUSION: This Delphi survey has been the first to identify criteria to be used in the annual appraisal of professionals. It has resulted in a number of criteria that could be considered for the appraisal and possible revalidation of colposcopists practising in UK.

Topical tacrolimus in the management of lichen sclerosus.

The effective management of vulval lichen sclerosus (LS) currently depends upon the use of topical steroids and emollients. There are concerns with regard to the long-term toxicity of potent steroids and therefore is a need to consider effective alternatives. Immunomodulatory macrolactams offer an alternative to steroids in the management of some other inflammatory skin disorders and it would seem reasonable therefore to assess their activity in LS. This pilot study of 16 histologically confirmed cases of LS suggests that macrolactams have a positive pharmacological effect.

Accuracy of magnetic resonance imaging of inguinofemoral lymph nodes in vulval cancer.

Inguinofemoral lymphadenectomy contributes to the high morbidity related to surgical treatment of vulval cancer. The objective of this study was to assess the accuracy of magnetic resonance imaging (MRI) in predicting inguinofemoral lymph nodes metastasis in women with vulval cancer. We reviewed the clinical, MRI, surgical, and pathologic findings of 59 women with vulval cancer who were treated at our institution from January 2000 to June 2004. Histology was available for 39 women who had undergone inguinofemoral lymphadenectomy. Clinical and MRI findings were compared with histology result to assess test accuracy. MRI had a positive likelihood ratio (LR+) of 4.8 (95% confidence interval of 2.7-8.6) and negative likelihood ratio (LR-) of 0.17 (0.06-0.49). It had a sensitivity of 85.7% (63.7-97), specificity of 82.1% (69.6-91.1), positive predictive value (PPV) of 64.3% (44.1-81.4), and negative predictive value (NPV) of 93.9% (83.1-98.7). Clinical examination had an LR+ of 6.1 (1.8-21.6) and LR- of 0.69 (0.5-0.96). It had a sensitivity of 35% (15.3-59.4), specificity of 94.3% (84.3-98.8), PPV of 70% (34.7-93.3), and NPV of 79.4% (67.3-88.5). Kappa statistics for interobserver and intraobserver agreement were 0.9091 and 0.8475, respectively. MRI assessment was accurate in predicting negative nodal status that is clinically useful in identifying women who can be spared inguinofemoral lymphadenectomy. It is noninvasive and is superior to clinical assessment. In clinical practice, this should encourage toward nodal sparing surgery, thus lowering surgical-related patient morbidity.

A systematic review of the accuracy of diagnostic tests for inguinal lymph node status in vulvar cancer.

OBJECTIVE: To determine the accuracy of minimally and non-invasive tests to assess the groin node status in squamous cell vulvar cancer. METHODS: A systematic review of published research from 1979 to 2004 that compares the results of tests to determine groin node status with histology at inguinofemoral lymphadenectomy was made. Studies included in the review were those that compared the index test to the standard surgical intervention of inguinofemoral lymphadenectomy and allowed the construction of two-by-two tables. From these tables, sensitivity, specificity, and the likelihood ratios (with 95% confidence intervals) were reported and, where feasible, meta-analysis was used to pool results for each test separately. Sentinel node biopsy using technetium-99m-labelled nanocolloid ((99m)Tc) had a pooled sensitivity and negative LR of 97% (91-100 95% CI) and 0.12 (0.053-0.28 95% CI), respectively, and was the most accurate test reviewed. CONCLUSION: Five diagnostic tests were identified in a total of 29 studies (961 groins). Although the studies were small and the design often poor, this represents the best summary of the data to date. Sentinel node identification using (99m)Tc appeared to be the most promising test for accurately excluding lymph node metastases in squamous cell vulvar cancer and potentially reducing the radicality of surgery. Its efficacy as a tool in reducing the need for radical surgery and associated patient morbidity without reducing survival needs further assessment probably in a randomised control trial.