Diagnostic evaluation of the endometrium in postmenopausal bleeding: an evidence-based approach.

Postmenopausal bleeding (PMB) is a common complaint in general gynecological practice. Women with PMB have around a 10% chance of having endometrial carcinoma and therefore PMB always needs further evaluation. This article summarizes the reviews on the subject and provides an overview of the use of diagnostic tools in patients with PMB. Four types of diagnostic test are described: sonographic measurement of endometrial thickness, endometrial sampling, hysteroscopy and saline infusion sonography. All four have been independently shown to be accurate in excluding endometrial cancer. However, neither in systematic reviews nor in international guidelines is consensus found regarding the sequence in which these methods should be employed in women with PMB. For measurement of endometrial thickness in symptomatic women, a cut-off value of 3mm is recommended, but the cost-effectiveness of this strategy has yet to be shown. Research should now focus on the incorporation of individual patient characteristics and pre-test probabilities for cancer in algorithms for the investigation of PMB, and the most cost-effective sequenced combination of the four types of test.

Long-term cervical cancer survivors suffer from pelvic floor symptoms: a cross-sectional matched cohort study.

OBJECTIVE: The aim of this study was to determine prevalence of and experienced distress from pelvic floor symptoms in cervical cancer survivors (CCS). METHODS: For this cross-sectional matched cohort study, we matched CCS, treated in the Academic Medical Center, Amsterdam between 1997 and 2007, to a random female population sample aged 20 to 70 years (reference group). We assessed prevalence of and distress from bladder and bowel symptoms with validated pelvic-floor-related questionnaires. Severe distress was defined as values above the 90th percentile of reference group's symptom domain scores. RESULTS: One-hundred and forty-six CCS underwent radical hysterectomy and pelvic lymph node dissection (RH and LND), 49 underwent surgery and adjuvant radiotherapy (SART), and 47 underwent primary radiotherapy (PRT). Urinary incontinence and obstructive voiding were reported by each treatment group more frequently than by the reference group and caused more distress. Patients treated with RH and LND reported more distress from most uro-genital symptoms, except from overactive bladder symptoms. Patients treated with PRT reported more distress from each uro-genital symptom than matched controls. The RH and LND group reported more distress from constipation and obstructive defecation than the reference group. Patients who underwent primary or adjuvant radiotherapy reported more distress from anal incontinence than their matched controls. CONCLUSIONS: Treatment of cervical cancer impairs pelvic floor function. Patients treated with PRT report the most adverse effects on pelvic floor function. The results of our study enable physicians to counsel accurately about specific symptoms. Furthermore, to facilitate referral to pelvic floor specialists when bothersome symptoms occur, we recommend evaluating pelvic floor symptoms as a standard during follow-up.

Reasons for not seeking medical help for severe pelvic floor symptoms: a qualitative study in survivors of gynaecological cancer.

OBJECTIVE: (1) To explore the reasons for not seeking help for severe pelvic floor symptoms after gynaecological cancer treatment. (2) To determine the willingness to undergo treatment for these symptoms. (3) To invite suggestions to improve outpatient care. DESIGN: Qualitative study using semistructured interviews. SETTING: Vulvar, endometrial or cervical cancer survivors treated in the Academic Medical Centre, Amsterdam, the Netherlands between 1997 and 2007. POPULATION: Purposively selected sample from 138 eligible respondents to pelvic floor-related questionnaires, who were severely bothered by their symptoms (>75th percentile of domain sum score of questionnaires) and had not sought medical help. METHODS: After each semistructured interview, a checklist with reasons for not seeking help was complemented with newly mentioned reasons. The interviews were stopped when data saturation was accomplished, i.e. three consecutive interviewees had not revealed new reasons. The interviews were analysed by two researchers independently. MAIN OUTCOME MEASURE: Help-seeking behaviour for bothersome pelvic floor symptoms. RESULTS: Fifteen interviews were conducted. Most reported reasons for not seeking help were that women found their symptoms bearable in the light of their cancer diagnosis and lacked knowledge about possible treatments. Seven women were willing to undergo treatment. Eleven women stated that care should be improved, specifically by timely referral to pelvic floor specialists and additional care by oncology nurses. CONCLUSIONS: There is a need for standardised attention to adverse effects on pelvic floor function after cancer treatment. This could be realised by quantifying symptoms using questionnaires, standardised attention for such symptoms by gynaecological oncologists or oncology nurses, and timely referral to pelvic floor specialists of women with bothersome pelvic floor symptoms.

Adjuvant radiotherapy in patients with vulvar cancer and one intra capsular lymph node metastasis is not beneficial.

AIM OF THE STUDY: The aim of the study was to analyze the benefit from adjuvant radiotherapy in patients with vulvar cancer and a single positive node without extra capsular spread. MATERIALS AND METHODS: The study population comprised data of 75 patients with vulvar cancer and one lymph node metastasis. The patients were treated in three different university centers in Amsterdam, Groningen and Rotterdam between 1984 and 2005. RESULTS: Out of 75 patients, 31 (41%) were treated with adjuvant radiotherapy. Both disease-free survival (DFS) and disease-specific survival (DSS) were comparable between the groups who did and who did not receive adjuvant radiotherapy (HR 0.98, 95% CI 0.45-2.14, p=0.97 and HR=1.02, 95% CI 0.42-2.47, p=0.96). CONCLUSION: We could not demonstrate any beneficial effect of adjuvant radiotherapy in the group of patients with one intra capsular metastasis.

A tool to balance benefit and harm when deciding about adjuvant therapy.

Adjuvant therapy aims to prevent outgrowth of residual disease but can induce serious side effects. Weighing conflicting treatment effects and communicating this information with patients is not elementary. This study presents a scheme balancing benefit and harm of adjuvant therapy vs no adjuvant therapy. It is illustrated by the available evidence on adjuvant pelvic external beam radiotherapy (RT) for intermediate-risk stage I endometrial carcinoma patients. The scheme comprises five outcome possibilities of adjuvant therapy: patients who benefit from adjuvant therapy (some at the cost of complications) vs those who neither benefit nor contract complications, those who do not benefit but contract severe complications, or those who die. Using absolute risk differences, a fictive cohort of 1000 patients receiving adjuvant RT is categorised. Three large randomised clinical trials were included. Recurrences will be prevented by adjuvant RT in 60 patients, a majority of 908 patients will neither benefit nor suffer severe radiation-induced harm but 28 patients will suffer severe complications due to adjuvant RT and an expected four patients will die. This scheme readily summarises the different possible treatment outcomes and can be of practical value for clinicians and patients in decision making about adjuvant therapies.

Partial urethral resection in the surgical treatment of vulvar cancer does not have a significant impact on urinary continence. A confirmation of an authority-based opinion.

Partial resection of the urethra is sometimes necessary in the surgical treatment of locally advanced vulvar cancer. In this study, the frequency of urinary incontinence after partial urethral resection was compared with that of patients who were treated without partial resection of the urethra. Eighteen patients with vulvar cancer encroaching or infiltrating the urethra, treated by a radical vulvectomy and partial urethrectomy, were compared with 17 patients treated by vulvectomy without partial removal of the urethra. Data on urinary incontinence pre- and postoperatively from both groups were retrospectively collected from the patient files. A questionnaire on urinary incontinence was sent to a subset of patients from both groups in order to get information on the current micturation pattern. In four out of 18 patients (22%) with a partial urethrectomy, incontinence was reported, versus two out of 17 patients (12%) in the control group (P= 0.860). Eight patients in the study group and 12 in the control group are currently alive, and all responded to the questionnaire. Two (25%) in the study group and three (25%) in the control group reported to have current symptoms of urinary incontinence. This retrospective study shows that partial resection of 1-1.5 cm of the distal urethra in addition to a radical local excision for vulvar cancer does not result in a significant increase in the frequency of urinary incontinence, compared with vulvar cancer patients without partial urethrectomy.

In the absence of (early) invasive carcinoma, vulvar intraepithelial neoplasia associated with lichen sclerosus is mainly of undifferentiated type: new insights in histology and aetiology.

BACKGROUND: Differentiated vulvar intraepithelial neoplasia (VIN) is presumed to be the precursor of invasive squamous cell carcinoma (SCC) of the vulva. It is commonly assumed that differentiated VIN is related to lichen sclerosus (LS). However, evidence for this is limited to a small number of studies describing epithelial alterations adjacent to vulvar SCC. AIM: To study the histology and human papillomavirus (HPV) status in patients with a history of both LS and VIN without coexistent SCC. METHODS: Original biopsy specimens and surgical specimens of patients retrieved from the pathology files were revised for the presence of LS, VIN and (early) invasive SCC, specifically focused on the two different types of VIN: differentiated and undifferentiated. Thereafter, VIN lesions were tested for the presence of HPV DNA. RESULTS: Twenty-seven patients fulfilled the criteria for LS and VIN without SCC. In all 27 patients, LS was found to be related to undifferentiated VIN. Grading yielded the following results: VIN 1 (n=10), VIN 2 (n=11) and VIN 3 (n=6). Additionally, VIN lesions from 26 patients could be tested for the presence of HPV DNA. HPV DNA, predominantly type 16, was present in 8 (31%) of them. Seven of these eight patients had VIN 2 or 3. During follow-up, three patients progressed to (early) invasive carcinoma. In two of these patients, differentiated VIN was observed overlying early invasive SCC. CONCLUSIONS: VIN related to LS without coexisting SCC is likely to be undifferentiated, in contrast to what was previously thought. HPV DNA was demonstrated in 31% of the lesions, and was strongly related to high-grade VIN.

Squamous cell cancer of the vulva with occult lymph node metastases in the groin: the impact of surgical technique on recurrence pattern and survival.

OBJECTIVE: The triple incision technique is an established surgical method of management for early vulvar cancer. There is only limited data available on the efficacy of this form of treatment for patients with occult inguinofemoral lymph node metastases. It was the objective of this study to obtain more insight into the efficacy of this treatment compared with the en bloc resection, when utilized in surgical pathological advanced disease. METHODS: A retrospective review was performed in patients with vulvar cancer in the presence of occult inguinofemoral lymph node metastases. Tumor diameter, extracapsular nodal spread, FIGO stage, number of positive lymph nodes, and type of treatment were analyzed in relation to recurrence pattern and survival in both univariate and multivariate analyses. RESULTS: There was no significant impact of surgical technique on disease-specific and overall survival. When corrected for other prognostic variables in a multivariate analysis, the type of surgical treatment was an independent predictor for vulvar recurrence (HR 0.10, 95% CI 0.02-0.44, P = 0.002) but not for inguinal/pelvic recurrence. CONCLUSION: The type of surgical technique did not influence disease-specific and overall survival in patients with occult inguinofemoral lymph node metastases. The triple incision technique is an independent poor prognostic variable for vulvar recurrence.

IgG antibodies against human papillomavirus type 16 E7 proteins in cervicovaginal washing fluid from patients with cervical neoplasia.

Little information is available about the cervicovaginal mucosal antibodies against human papillomavirus (HPV) proteins. In this study specific IgG antibodies against HPV 16 E7 protein were determined in paired samples of cervicovaginal washing fluid and serum from patients with cervical cancer (n = 22), cervical intraepithelial neoplasia (CIN) (n = 38), healthy individuals (n = 22), and serum from children (n = 41) by a radioactive immunoprecipitation assay (RIPA). HPV 16 E7 specific IgG antibodies were found in cervicovaginal washings (n = 8) and in sera (n = 8) of the patients with cervical cancer. About 60% of the patients with HPV 16 positive cervical cancer had HPV 16 E7 specific IgG antibodies. Titration studies showed that the IgG antibody reactivity in cervicovaginal washings was higher than in the paired serum samples of six patients with cervical cancer (P < 0.001). In the CIN group we found no IgG reactivity in the serum, but in five patients we found a low IgG reactivity in the cervicovaginal washings. No IgG reactivity was found in cervicovaginal washings and sera from healthy individuals and sera from children. HPV 16 E7 specific IgG antibodies seem to be locally produced in a number of patients with HPV 16 positive (pre)malignant cervical lesions. For more definitive evidence for the local production of these antibodies immunostaining should be performed to demonstrate the presence of specific anti-HPV 16 E7 IgG producing plasma cells in the cervical epithelium.

Squamous cell carcinoma of the vagina: a report of 32 cases.

Between 1982 and 1992, 32 patients with squamous cell vaginal cancer were treated. Fourteen patients had stage I, 11 stage II, two stage III and five stage IV disease. The mean age of stage I and II patients was 64, of stage III and IV patients 73. Six patients were pessary-bearing, two had a total procidentia, eight had been treated for cervical intraepithelial neoplasia (CIN), one for cervical cancer and one for vulvar cancer 5-21 years before diagnosis. One patient had had external irradiation for endometrial cancer 15 years before. Nine patients had no follow-up examinations after treatment for CIN, for vulvar cancer or after insertion of a pessary. In 14 patients doctors' or patients' delays were considerable. Most patients presented with vaginal discharge or bleeding, and urinary symptoms. Various treatment modalities were used. The selected patients who could be treated by surgery did best. Only patients with a stage I tumor or a stage II tumor with a diameter of at most 30 mm survived. Tumor stage and tumor diameter were the important prognostic factors. No patient died of disease after 33 months. Failure in obtaining local control was the usual cause of death. Recommendations for prevention or early diagnosis are formulated.

The reliability of the histologic diagnosis in colposcopically directed biopsies. A plea for LETZ.

A total of 121 patients with cervical intraepithelial neoplasia (CIN) in their punch biopsies were treated by LETZ. In all cases, the transformation zone was fully visible and there were no signs of abnormal cylindrical epithelium. The final diagnosis was classified in accordance with the histologic report showing the most severe lesion. The biopsy diagnosis underestimated the final diagnosis in 27 out of the 121 cases. Invasion was present in five out of these 27 cases. The discrepancies between the biopsy diagnosis and the final diagnosis were not related to the number of colposcopically directed biopsies. It is concluded that an important advantage of LETZ, as compared with tissue-destructive techniques, is the detection of previously unrecognized invasive disease.