Vulvar intraepithelial neoplasia--the need for auditable measures of management.

OBJECTIVES: Surgical excision is currently the standard treatment for vulvar intraepithelial neoplasia (VIN). To date it has proved difficult to evaluate the management of VIN in reported series due to heterogeneity in datasets. The objective of this study was to justify standardised data presentation to permit comparison between series and facilitate determination of an optimal strategy for management of VIN. We propose auditable indicators of performance to benchmark management and outcomes. This may also enable definition of a surgical control arm for future novel therapy studies. STUDY DESIGN: Data from the Northern Gynaecological Oncology Centre (NGOC), UK on women with proven VIN diagnosed between 1989 and 2004 who attended the vulvar review clinic are presented and analysed alongside three large retrospective series by Jones et al. [Jones RW, Rowan DM, Stewart AW. Vulvar intraepithelial neoplasia: aspects of the natural history and outcome in 405 women. Obstet Gynecol 2005;106(6):1319-26], Herod et al. [Herod JJ, Shafi MI, Rollason TP, Jordan JA, Luesley DM. Vulvar intraepithelial neoplasia: long term follow up of treated and untreated women. Br J Obstet Gynaecol 1996;103(5):446-52], McNally et al. [McNally OM, Mulvany NJ, Pagano R, Quinn MA, Rome RM. VIN 3: a clinicopathologic review. Int J Gynecol Cancer 2002;12(5):490-5] against proposed performance indicators to illustrate the deficiencies in current data presentation. RESULTS: Demographics and indicators such as degree of pathological expertise, definition of early stromal invasion and use of International Society for the study of Vulvovaginal Disease (ISSVD) classification were usually well documented. The description of lesions including size and focality were not always documented, nor the proportion examined by co-specialists. Numbers of primary treatments were well described but the indications for treatment, completeness of excision and VIN subclassification were not. Subsequent surgical treatments were inconsistently reported including the pathological details and intervals between treatments. Symptomatology was not well reported. Information on follow-up intervals and duration of follow-up with an indication of patient compliance was inadequate. Outcome data on recurrence of VIN and progression to carcinoma (early stromal invasion or frankly invasive carcinoma) were included in all series. CONCLUSIONS: Consensus on the ideal management of VIN or evaluation of new strategies will prove impossible without standardised data presentation. We propose a number of performance indicators that will facilitate evaluation of future studies or series against the current benchmark of surgical treatment for VIN.

The effect of epithelial and stromal tumor components on FIGO stages III and IV ovarian carcinosarcomas treated with primary surgery and chemotherapy.

The aim of this study is to assess the effect of epithelial and stromal tumor components on survival outcomes in FIGO stage III or IV ovarian carcinosarcomas (OCS) treated with primary surgery and adjuvant chemotherapy at the Northern Gynaecological Oncology Centre (NGOC), Gateshead. Women were identified from the histopathology/NGOC databases. Age, FIGO stage, details of histology, treatment, and overall survival were recorded. Of 34 cases (1994-2006, all FIGO stages), 17 were treated with primary surgery followed by adjuvant chemotherapy for FIGO stage III or IV. The median age was 66 years (52-85 years). Cytoreduction was optimal (n= 9) or complete (n= 1) in 10/17 (59%) cases. Epithelial predominant (EP) or stromal predominant (SP) tumor (defined as >50% of either component in the primary tumor) was noted in 12 and 5 cases, respectively. Epithelial types included serous (n= 9), endometrioid (n= 5), and mixed types (n= 3). Twelve women have died of disease. The median overall survival was 11.0 months (3-74 months). On univariate analysis, survival was not affected by optimal/suboptimal debulking, platinum/doxorubicin-containing chemotherapy, or homologous/heterologous stromal components. Stromal components (>25%) adversely affected survival (P= 0.02), and there was a trend to worse survival with serous compared with nonserous epithelial components (P= 0.07). Cox regression (multivariate analysis) showed that SP tumors (P= 0.04), suboptimal debulking (P= 0.01), age (P= 0.01), and tumors with serous epithelial component (P= 0.05) were adverse independent prognostic factors. Type of chemotherapy and homologous/heterologous components (P= 0.24) did not affect overall survival. In conclusion, our study suggests that SP-OCS have a worse survival outcome than EP tumors. Tumors with serous epithelial components adversely affected the survival compared with nonserous components. Larger studies are required to confirm these effects and to identify the optimum chemotherapy regimen for OCS.

Recurrent smear abnormalities where repeat loop treatment is not possible: is hysterectomy the answer?

OBJECTIVE: The objective of this study was to determine the outcome of women who underwent hysterectomy for recurrent cytological abnormalities where repeat loop treatment was considered not to be technically possible because of insufficient remaining cervical tissue. METHODS: Women undergoing a hysterectomy for the above indication at the Northern Gynaecological Cancer Centre over a period of 10 years (1992-2001) were identified from a prospectively collected database. Case notes were then reviewed and women undergoing hysterectomy for other indications were excluded. Relevant demographic and clinical data were then extracted. RESULTS: 33 patients meeting the above criteria were identified. The overall hysterectomy rate for this indication was 0.73%. 20 out of the 33 women had significant pathology on the hysterectomy specimen. 95% of these had high-grade disease with one having a Stage 1A1 squamous carcinoma. None of the patients required more radical treatment than a simple hysterectomy. There were no major complications following the hysterectomy. Positive endocervical margins on the previous loop specimen (P = 0.05) was an important correlating factor predicting the presence of CIN on the hysterectomy specimen. One out of the thirty hysterectomies (3.3%) performed using the vaginal route had incomplete excision compared to one of three (33%) using the abdominal route. Hysterectomy was successful in treating 85.2% of the women; only 4 women subsequently developed vaginal intraepithelial neoplasia. CONCLUSION: Simple hysterectomy appears to be a suitable diagnostic and treatment option for women with recurrent high-grade cytological abnormalities where further loop treatment is technically not possible. Incomplete excision at the endocervical margin on the previous loop specimen was the main factor associated with the presence of cervical intraepithelial neoplasia at hysterectomy.

Uterine inversion by a mixed müllerian tumor of the corpus.

Mixed müllerian tumors (MMT) of the uterus have been reported following the use of tamoxifen. Rarely, these tumors lead to an uterine inversion. The surgical approach of a uterine inversion forms a therapeutic challenge. In this article, a case of uterine inversion due to a MMT is reported, together with a literature review regarding the developing mechanisms and management.

Port-site recurrence following laparoscopic surgery in cervical cancer.

Port-site metastasis (PSM) after laparoscopic lymphadenectomy in cervical cancer is a new phenomenon. This situation creates potential therapeutic difficulties, especially in node-negative and early stages of disease. We report a case of port-site metastases following laparoscopic removal of para-aortic lymph nodes in a 74-year-old women with stage IIIb squamous cancer of the cervix, together with an update of all the previous published cases in the literature. None of the removed lymph nodes showed evidence of metastatic carcinoma. The patient received radiation therapy and a complete response was accomplished. Fifteen months after the operation, the patient presented with a suspicious lesion around the umbilical port-site. The lesion was excised and histology confirmed metastatic disease. The patient was further treated with cisplatin. However, she died of her disease after 24 months. The development of a port-site recurrence after laparoscopic surgery in cervical cancer could jeopardize use of this approach. Therefore, all patients undergoing laparoscopic surgery for malignancies should have careful follow-up with special attention to the port sites.

The feasibility of a one-stop colposcopy clinic in the management of women with low grade smear abnormalities: a prospective study.

OBJECTIVES: To assess the feasibility of a one-stop colposcopy clinic for the management of women with low-grade smear abnormalities. Secondly, to determine whether the approach of immediate information of biopsy results combined with treatment if indicated helps to reduce patient anxiety and improve overall patient satisfaction with the colposcopy process. DESIGN: Prospective study following the introduction of a "one-stop" process for the management of women with low grade smear abnormalities. SUBJECTS: First 118 women managed in a "one-stop" clinic during an 8-month period. METHODS: Assessment of patient anxiety via self-completed questionnaires and comparison of anxiety scores with a control group managed via a standard clinic. RESULTS: The median waiting time for results in the one-stop clinic was 120 min (range: 100-165). All women in both groups felt anxious at the time of the clinic visit. However, after 1 week the majority of patients managed via the one-stop process felt slight anxiety only (P=0.0001) as opposed to those patients in the control group who remained anxious (P=NS). In addition, all women said they would prefer the one-stop approach for further smear abnormalities if a further colposcopic examination was warranted. CONCLUSION: A one-stop colposcopy clinic is feasible for the management of women with low-grade smear abnormalities. In addition, it delivers a quality service, optimises patient management, reduces anxiety and is the patient's choice.

Inguinal lymph node metastasis: an unusual presentation of fallopian tube carcinoma.

OBJECTIVES: Inguinal metastasis is a hitherto unreported presenting feature of fallopian tube adenocarcinoma. CASE: We describe a case of a 69-year-old patient whose first manifestation of fallopian tube adenocarcinoma was an enlarged inguinal lymph node. This was excised and confirmed to be metastatic adenocarcinoma. She was investigated by diagnostic laparoscopy and subsequently underwent laparotomy with total abdominal hysterectomy, omentectomy, and pelvic and para-aortic lymph node dissection. All but two of the lymph nodes extirpated were negative. CONCLUSIONS: Fallopian tube adenocarcinoma may rarely present with metastatic inguinal lymphadenopathy.

The role of surgery in invasive squamous carcinoma of the vagina.

OBJECTIVE: The aim of this study was to define the role of surgery in managing patients with a primary squamous vaginal cancer. METHODS: A retrospective review was conducted of patients with primary invasive vaginal cancer managed at one institution over a 25-year period. The results were compared with those of all major publications of the past 20 years. RESULTS: A total of 84 patients were reviewed. Forty-five (66%) were of squamous origin. The median follow-up was 45 months (range: 0.6-268). The patients were primarily treated by surgery in 67% and by radiotherapy alone in 33% of cases. The 5- and 10-year overall survival was, respectively, 74 and 58%. For stage I the figures were 91 and 70%. These survival rates compared favorably with those of published series of cases managed by radiotherapy alone. Univariate analysis showed that age (P = 0.004), size (P = 0.009), site (P = 0.016), lymph node status (P = 0.022), FIGO stage (P = 0.027), and treatment (P = 0.003) were relevant prognostic factors. Multiple regression analysis, however, revealed that only age (P = 0.009) and size (P = 0.037) were independent prognostic variables. CONCLUSIONS: Stage I and II squamous vaginal cancer patients have good outcomes in terms of survival and local tumor control if they are managed by initial surgery followed by selective radiotherapy.

Do elderly cancer patients care about cure? Attitudes to radical gynecologic oncology surgery in the elderly.

OBJECTIVE: The aim of this study was to address the hypothesis of no difference between elderly and younger patients' desire for optimal surgery and disease cure. METHODS: The new ARGOSE questionnaire with established instruments was administered to 189 gynecologic cancer patients (95 aged <65, 57 aged 65-74, and 37 aged 75+ years). RESULTS: Disease diagnosis differed between the <65 years and 65+ years cohorts (P < 0.001), but treatment modalities were similar (P = 0.28). Influences of family and friends and past experiences of cancer had little influence on treatment decisions. There was no difference between cohorts in desire for surgery offering a chance of disease cure (P = 0.75), except that the elderly desire cure more if treatment is associated with disfigurement than do the young. (P = 0.029). The elderly believe more strongly than the young that the elderly value cure (P < 0.001). Issues of sexuality and femininity associated with gynecologic cancer and treatment are more important to younger patients (P < 0.001). The elderly support equality of care with relation to age more strongly than the young. However, in a situation of resource limitation, inequality favoring the young is opposed less strongly by the elderly than by the young. Social desirability bias may have influenced this finding. All cohorts reported symptom palliation to be of secondary importance to treatments offering a possibility of cure (P = 0.26). The elderly believe more strongly that doctors should make management decisions (P < 0.001). CONCLUSION: The elderly desire radical surgery and disease cure as strongly as the young. They are less likely to question their doctors' decisions and are therefore vulnerable to physicians' age bias. There is no justification for rationing care on the basis of chronological age.

Primary vaginal melanoma and long-term survivors.

Vaginal melanoma is a rare and highly malignant disease. This report describes the characteristics and clinical course of all patients treated at one institute (Northern Gynaecological Oncology Centre, UK) over the last 25 years. Of a total of nine patients identified with a primary malignant vaginal melanoma, only one patient survived for more than five years. A literature review revealed only 21 reported cases with a survival greater than five years. The most important factor for survival appears to be the tumour size. Treatment modality varied equally within the group of long-term survivors (27% radical surgery, 27% wide local excision, 27% radiotherapy, 14% wide local excision and radiotherapy, and 5% unknown therapy). The prognosis of patients with primary malignant melanoma is poor, regardless of primary therapy (conservative or radical). Conservative treatment and accurate investigation of every discoloured lesion is recommended.

Prevalence and management of (non-fistulous) urinary incontinence in women following radical hysterectomy for early stage cervical cancer.

OBJECTIVES: 1) to determine the prevalence of urinary incontinence before and after radical surgical treatment for early cervical cancer, 2) to retrospectively analyse the outcome results following the investigation/treatment of incontinence in these women. PATIENTS AND METHODS: 27 women were studied prospectively by questionnaire prior to surgery and six weeks and three months after surgery (group 1). Seventy-seven women who were more than 12 months post-radical surgery were questioned directly at the follow-up clinic (group 2). Three hundred and two satisfactory responses were obtained to questionnaires sent to general practitioners of patients previously treated by radical surgery for early cervical cancer (group 3). RESULTS: 14.8% of women reported regular incontinence prior to surgery, and 48.1% and 29.6% of women, respectively, reported regular incontinence six weeks and three months after surgery; 31.2% of women also reported regular incontinence more than 12 months after post-radical surgery. Of the women in the 12-month post-radical surgery group, 16.6% had considered their symptoms of regular incontinence severe enough to attend their local practice for treatment and 14.6% (44 women) were referred for further management. In six of these 44 patients (13.6%), spontaneous resolution of incontinence occurred at varying intervals within the first 12 months following radical surgery. Twenty-four of the 44 women who were referred underwent urodynamic investigation. Of these 24 women, in 17 cases the diagnosis was genuine stress incontinence (GSI), of which, in seven cases (41%) GSI was the sole urodynamic abnormality. In six of these seven cases (85.7%), the women were cured or very greatly improved following treatment with either physiotherapy or surgery. However, only six of the remaining ten cases (60%) with coexistent abnormalities achieved this result. Patients with coexistent impaired bladder compliance showed the poorest result, as only two of the six cases (33%) achieved satisfactory improvement following treatment. CONCLUSION: Non-fistulous urinary incontinence following radical pelvic surgery for carcinoma of the cervix despite being a common problem shows a significant spontaneous improvement rate within the first 12 months following surgery. Urodynamics should be a mandatory investigation in patients who complain of persisting problems thereafter. Subjective improvement rates for women with genuine stress incontinence alone are in excess of 85%, being comparable to those of women without any prior history of radical pelvic surgery.

Does long-term follow-up have a role for node negative squamous carcinoma of the vulva? The Gateshead experience.

A retrospective review was performed of 138 cases of squamous vulval cancer referred to Gateshead between 1986 and 1997, with a median follow-up of 48 months. Eighteen recurrences were detected, 11 within one year of surgery. All nine patients with groin/distant recurrence (including 4 presenting initially with local recurrence only) died of vulval cancer. Vulval pain, bleeding or other symptoms heralded all recurrences. Routine review was ineffective in detecting recurrence. Eight cases were detected by general practitioners, three by specialists, and one was self-diagnosed. Six of these had had clinical review less than two months previously. Follow-up does not appear to offer early detection or survival advantages. Patient education, with symptom-triggered rapid clinic access, may be more effective. Prospective research is indicated to assess both the effectiveness and psychological implications of routine follow-up and alternative strategies.

Risk factors in stage III epithelial ovarian cancer: previous sterilisation is an adverse independent prognostic indicator.

OBJECTIVES: To determine whether past history of pelvic surgery is of prognostic significance in stage III epithelial ovarian cancer. METHODS: A retrospective review of 140 women with stage III epithelial ovarian cancer. RESULTS: Sixteen women had previously undergone pelvic surgery including eight sterilisations (6%), seven hysterectomies (5%) and one ovarian cystectomy (0.7%). Women with a past history of sterilisation were significantly younger (median age, 46 years) than women without a past history of sterilisation (median age, 63 years), and also significantly younger than women with a past history of hysterectomy (median age, 58 years). In addition, the sterilisation procedure was performed at a significantly younger age than the hysterectomy procedure (p=0.008). On multivariate analysis comparing previous pelvic surgery, previous malignancy, place of surgery, interval/secondary debulking, presence of concomitant tumour, performance of bowel surgery, histological grade, histological type, size of residual disease and age, all of the following were seen to be independent variables associated with outcome survival; previous sterilisation (p=0.0012), age (p=0.0074), histological type (p=0.025), histological grade (p=0.0017) and size of residual disease (p=0.0043). CONCLUSION: Past history of sterilisation appears to be an adverse independent prognostic indicator in women presenting with stage III epithelial ovarian cancer. To have developed ovarian cancer despite the protective effects of a sterilisation procedure against environmental factors might possibly suggest a predisposition to ovarian cancer in these women. Further studies are indicated to confirm the present results.

Complete cytoreduction: is epithelial ovarian cancer confined to the pelvis biologically different from bulky abdominal disease?

OBJECTIVES: The aim of this study was to determine whether site and size of tumor masses prior to complete surgical cytoreduction affect outcome survival. METHODS: A retrospective review was performed of 53 women with stage II and III epithelial ovarian cancer following complete surgical cytoreduction. RESULTS: Fifteen cases (28%) were classified as stage II and the remaining 38 cases (72%) as stage III. The overall median survival was 58 months with overall 2- and 5-year survivals of 76 and 42%, respectively. On univariate analysis, women with well differentiated tumors did significantly better than those with moderately or poorly differentiated tumours (P = 0.0009). FIGO stage did not reach statistical significance (P = 0.066). On multivariate analysis, comparing patient's age, previous history of pelvic surgery, previous history of malignancy, performance of lymphadenectomy for visibly/palpably enlarged nodes, performance of bowel resection, presence of concomitant tumors, positive pelvic and/or para-aortic lymph nodes, histological type, histological grade, and FIGO stage, only histological grade remained an independent variable affecting outcome survival (P = 0.0004; FIGO stage, P = 0.22) (hazard ratio = 6.5: well versus poor differentiation, 95% confidence interval, 1.7-25.5). CONCLUSION: When surgical cytoreduction to no visible disease has been achieved in women with stage II and III epithelial ovarian cancer, FIGO stage, i.e., site and size of tumor masses prior to surgical cytoreduction, does not appear to influence outcome survival. The aggressiveness of the remaining microscopic disease would seem to be determined largely by histological grade. Bearing in mind the retrospective nature of this study and the relatively small cohort of patients, the results would appear to suggest that it is unlikely that there are any other significant parameters (hidden factors) affecting tumor biology which are independent of tumor grade in these patients. A possible implication of this result is that complete surgical cytoreduction confers a survival benefit by producing a biologically more homogeneous tumor.

Optimal cytoreductive surgery is an independent prognostic indicator in stage IV epithelial ovarian cancer with hepatic metastases.

OBJECTIVES: The aim of this study was to determine the value of optimal cytoreduction in stage IV epithelial ovarian cancer. METHODS: A retrospective review was performed of 37 women with stage IV epithelial ovarian cancer treated by radical surgery. RESULTS: Optimal surgery to less than 2 cm tumor deposits was performed in 16 of the 37 cases (43%) and tumor debulking to less than 1 cm tumor deposits in 6 cases (16.2%). Twenty-three cases (62%) were designated stage IV because of the presence of liver metastases alone. Although no patients died within 2 weeks of surgery, 7 of the 37 cases (22%) failed to survive more than 50 days after primary surgery. The overall median survival was 11 months with overall 2- and 5-year survivals of 23 and 9%, respectively. On multivariate analysis comparing age, histological type, tumor grade, place of surgery, secondary surgical procedure, performance of bowel surgery, presence of liver metastases, and optimal cytoreduction, only optimal surgery and residual tumor deposits of less than 2 cm, or less than 1 cm, remained highly significant (P = 0.0029 and 0.0086, respectively). Even when assessing only the 27 cases who were designated as having stage IV disease because of the presence of liver metastases, by multivariate analysis, only optimal surgery and residual tumor deposits of less than 2 cm, or less than 1 cm, remained significant (P = 0.023 and 0.036, respectively). Site of metastases designating stage IV status was not associated with a reduced likelihood of achieving optimal debulking (P = 0.18). CONCLUSION: Optimal cytoreduction in women with stage IV epithelial ovarian cancer with or without hepatic metastases is associated with a more favorable outcome survival.

Attitudes to radical gynecological oncology surgery in the elderly: a pilot study.

Does age-related inequality of cancer care reflect patient preference or physician prejudice? We hypothesize no difference between elderly and younger patients' desire for optimal surgery and disease cure, and psychological adaptation to cancer. A newly developed questionnaire to assess attitudes to radical gynecological surgery in the elderly (ARGOSE) and a battery of established instruments were administered to 54 gynecological cancer patients (32 aged 65 + years; and 22 aged < 65 years) by structured interview. Disease diagnosis differed between cohorts (P = 0.007), but treatment modalities were similar (P = 0.46). There was no difference between cohorts in desire for optimal surgery and disease cure. Trends suggest the young consider a patient's age is less important than do the elderly, but the elderly may oppose age-related economic rationing of treatment more than the young. Furthermore, elderly individuals tend to perceive their seniors too elderly for treatment, but not themselves. The elderly believe more strongly that doctors should make management decisions. Perceptions of change in body image after cancer treatment did not differ between cohorts. The influence of age in determining attitudes is complex. A larger study with increased power is indicated to examine trends revealed in this pilot study.

Identification of sentinel lymph nodes in vulvar carcinoma patients with the aid of a patent blue V injection: a multicenter study.

BACKGROUND: The aim of this multicenter study was to investigate the feasibility and negative predictive value of sentinel lymph node detection with blue dye in vulvar carcinoma patients. METHODS: In patients with squamous cell carcinoma of the vulva without suspicious groin lymph nodes, patent blue V was injected intradermally shortly before surgery. Routine groin lymph node dissection and radical vulvectomy were performed. During the surgery, blue lymph vessels and lymph nodes were identified, and the blue lymph nodes were sent separately for histologic examination. The negative predictive value of the blue lymph nodes for the absence of metastases was assessed by histologic examination of the groin lymph node specimens. RESULTS: Fifty-one patients in whom 93 groin lymph node dissections were performed were entered. One or more blue lymph nodes were detected in only 52 groins (56%). Nine (17%) of these were tumor positive, and 6 blue lymph nodes were the only tumor positive lymph nodes in the specimen in which they were found. There were two false-negative blue lymph nodes. The negative predictive value was 0.953. CONCLUSIONS: It was shown in this multicenter study that sentinel lymph node detection in vulvar carcinoma patients with blue dye only is not feasible because its negative predictive value is too low. Further studies involving the use of a combination of radioactive labeled technetium and blue dye are warranted.