Objective. To determine the incidence of parametrial involvement in clinical stage IA and IB1 cervical cancer and whether pelvic lymph node status is a predictor of parametrial status.Methods. Retrospective review of 120 patients with FIGO stage IA/IB1 cervical carcinoma treated by class 11 radical abdominal hysterectomy between January 1997 and December 2001 was performed. The parametria were examined for microscopic involvement of parametrial lymph nodes and/or tissue. Continuous variables were compared using Wilcoxon rank sum test, and Fisher's exact test was used to categorical variables. Kaplan-Meier curves were constructed for overall survival (OS) and recurrence-free survival (RFS). Cox proportional hazards model was used to investigate prognostic factors.Results. One hundred ten patients were eligible. Five patients (5%) had positive parametria and 13 patients (12%) had positive pelvic lymph nodes. Four (80%) patients with positive parametria had positive pelvic lymph nodes. The groups did not differ significantly in terms of age (P = 0.92), histology (P = 0.15), or LVSI (P = 0.20). Positive parametria was associated with larger tumor size (3.0 vs. 2.0 cm, P < 0.05), greater depth of invasion (16 mm vs. 5 mm, P = 0.03), and pelvic lymph node metastases (80% vs. 10%, P = 0.001). The only variable that was significant in the proportional hazards model was lymph node status (P = 0.02). After median follow-up of 48 months, there was a significant difference in recurrence (40% vs. 4%, P = 0.03) and RFS (0.0003).Conclusions. Acknowledging small sample size and retrospective study, positive parametrial involvement in stage IA and IB1 cervical cancer is infrequent. There is a significant association with lymph node status. Thus, there may be a role for less radical surgery combined with pelvic lymphadenectomy in this patient population. (c) 2006 Elsevier Inc. All rights reserved.

OBJECTIVE:To determine the association between atypical glandular cells (AGC) on Pap smear and clinically significant histology, in a large health region.METHODS:A cytologic database of over one million Pap smears was reviewed for a result of AGUS/AGC. Cytologic and histologic follow up was obtained to establish the presence of significant histology.RESULTS:456 patients available for follow up had AGUS/AGC cytology results (0.043% of all Pap smear results). 197(45.2%) patients had a clinically significant diagnosis including 40 with adenocarcinoma in situ (AIS) of the cervix and 48 with endometrial cancer.CONCLUSION:AGC on a Pap smear is frequently associated with a clinically significant diagnosis.

OBJECTIVE:The purpose of this study was to compare early oral intake and the traditional timing of feeding after major gynecologic surgery and the effects on the length of hospital stay.STUDY DESIGN:Gynecologic oncology and urogynecology patients who underwent major abdominal gynecologic surgery were prospectively randomized to 1 of 2 groups. The traditional feeding group (group A, 49 patients) received nothing by mouth until documentation of bowel function. They were then advanced slowly to solid diet. The patients allocated to the early feeding regimen (group B, 47 patients) began clear fluids on the first postoperative day. Once 500 mL of clear fluid was tolerated, they received a regular diet. The groups were compared with regard to length of hospital stay, postoperative day that solids were tolerated, and the incidence of adverse effects. Statistical analyses were performed with the chi(2) test, the Fisher exact test, the Student t test, and analysis of variance.RESULTS:The demographic characteristics of the 2 groups were similar. There was a statistically significant reduction in the length of hospital stay for those patients on the early feeding regimen. The median length of stay for group A was 6.0 days and for group B was 4.0 days (P =.0001). There was no difference in the incidence of emesis, ileus, or other postoperative complications between the 2 groups.CONCLUSION:Early postoperative dietary advancement after major abdominal gynecologic surgery results in a decreased length of hospital stay and appears to be safe, with no increased adverse effects.

The objective of this research is to assess the use of first-line postoperative chemotherapy in patients with advanced ovarian granulosa cell tumor (GCT). A retrospective population-based case series identified 60 women with stage IC or greater ovarian GCT over a 25-year period. Five patients were excluded because of incomplete information. None of the patients had received chemotherapy or radiotherapy prior to the diagnosis of advanced GCT. All patients had, at a minimum, a total abdominal hysterectomy and bilateral salpingo-oophorectomy. Pathology was centrally reviewed and the diagnosis confirmed. Of the 55 eligible patients, the 21 women with stage III and IV disease were the main focus of the study. Clinical outcomes and survival were compared between 13 women who received combination chemotherapy and eight who did not. Univariate analysis was conducted to assess the impact of age at diagnosis, size of residual disease, and adjuvant use of radiation therapy on prognosis. For the 55 patients, median age at diagnosis was 54 years (range 22-79). Median length of follow-up was 4.4 years (range 0.3-23.3). Median time to progression was 2.3 years (range 0.3-5.3). Sixty percent of those with no macroscopic disease after primary surgery recurred within 4.5 years of diagnosis. All patients with gross residual disease (>2 cm) were dead within 4 years of diagnosis. Overall 5 years survival rate was 61.6% (95% CI (49.3-76.9)). Among stage III and IV patients, there were no differences with respect to age at diagnosis and use of radiation therapy between those who did and did not receive chemotherapy. The only statistically significant difference was the presence of macroscopic residual disease (82% vs. 22%). Although there was no statistical significant difference in overall survival, there was a trend toward a poorer outcome in the group that received chemotherapy. Survival of patients with macroscopic residual disease was not influenced by use of chemotherapy (P = 0.976). We conclude that the presence of macroscopic residual disease after primary surgery was the most important prognostic factor. Although these patients were more likely to receive postoperative chemotherapy, there was no evidence to document a beneficial effect of systemic therapy in this group of women.

Approximately 20-40% of lesions interpreted by a screening Pap test as CIN I and subsequently examined by colposcopy include a co-incidental CIN II/III. Since the HPV profiles of CIN I and CIN II/III differ, HPV typing may predict these co-incidental higher grade lesions. Based on both the colposcopic impression and repeat Pap test, 537 women referred for examination of CIN I as classified by a screening Pap test were triaged into group A (= CIN I) or group B (>/= CIN II). Clinical, demographic, reproductive, and risk factor data was collected by questionnaire and HPV typing of cervical scrapes was done by PCR. Group A included 342 (63.7%) women and group B 195 (36.3%). Group B women more frequently were current cigarette smokers (p<0.001) and had a high school or lesser level of education (p=0.04). HPV positivity amongst younger group B women (= 21 years) and a history of current/occasional cigarette smoking in those 22 years and older were significant predictors of triaged, co-incidental CIN II/III (p<0.001). This age restriction will limit the adoption of HPV testing as an universal, adjunctive test for the identification of CIN II/III amongst CIN I lesions detected by a screening Pap test. A greater health advantage may be gained by increasing women's awareness of the risks, including that of cervical cancer associated with cigarette smoking.

The published literature indicates 11% of CIN I lesions on average progress to a higher grade dysplasia and the remainder either regress or persist. Reliable markers of disease outcome are yet to be identified. A longitudinal study of 342 women referred for colposcopic examination of a CIN I detected by a screening Pap test, and classified by the colposcopic impression and Pap test at that exam as </= CIN 1 was designed to identify predictors of disease outcome. The cohort was comprised of 220 women who satisfactorily completed the study and whose disease was neither biopsied or treated at the initial examination. All had HPV DNA testing by PCR, and were followed with interval colposcopic examinations and repeat Pap tests for a limited time period. The initial HPV DNA status and a number of measured clinico-pathological and risk factor variables were analyzed to identify outcome predictors. All underwent a biopsy either at the conclusion of the study or because their disease was considered to have progressed during the follow up period. Biopsy confirmed progression to CIN II/III occurred in 41 (18.6%), persistence of CIN I/Condyloma in 41 (18.6%), and regression to <CIN I/Condyloma in 138 (62.7%). HPV DNA positivity and current, oral contraceptive use were the only independent predictors of progression when age at diagnosis, the number of follow up visits, and time to progression were controlled. Predictors of persistent and regressed disease were not identified. The study highlights a clinical role for HPV testing in the colposcopic management of CIN I lesions. Oral contraceptives may promote progression by regulating the oncogenic sequences of the HPV.

Correlates of HPV amongst a cohort of women with a CIN I detected by a screening Pap test were investigated. Co-incident CIN II/III lesions were identified and their influence on the HPV status and HPV determinants of screening detected CIN I was assessed. Based on both the colposcopic impression and repeat Pap test, 537 women referred for examination of a Pap test classified as CIN I were triaged into two groups. Group A lesions were assessed as = CIN I; n = 342 (63.7%) and group B as >/= CIN II; n = 195 (36.3%). Clinical, demographic, reproductive, and risk factor for cervical cancer correlates were collected. HPV typing of cervical scrapes collected at the colposcopic examination was done by PCR amplification using seven sets of type specific and one set of consensus primers. HPV positivity was identified in 47% of all scrapes; types 16/18 (28%), 31/33/35 (10%), 6/11 (2%), and unknown (7%). The HPV status of the cohort and group A were very similar. Group B had a slightly higher rate of HPV positivity (52%) due to an increase in types 16/18. Statistically significant correlates of HPV prevalence or type were not identified either for the entire group or both triage groups, however in each group, HPV positive women tended to be younger and to have more sexual partners. Co-incident CIN II/III spuriously increased the HPV prevalence rate of CIN I detected by a screening Pap test. The HPV appears to be sexually transmitted both in low and high grade lesions and explains why the HPV determinants of the entire cohort were unaffected by the co-incident CIN II/III.

The rate of Human Papillomavirus (HPV) detection in CIN 1 lesions is quite variable for several reasons. Amongst these, the sensitivity level of the HPV detection system probably ranks supreme. The prevalence of HPV DNA in cervical scrape samples from 234 patients referred for colposcopic investigation of a CIN 1 lesion was compared using dot blot hybridization (DBH) and polymerase chain reaction (PCR) amplification. Both methods were performed on the same patient sample so that determinants of HPV positivity other than the detection system could be controlled. Probes and primers to HPV 6, 11, 16, 18, 31, 33, and 35, and consensus HPV primers were used. The overall HPV positivity rate was 24% using DBH and 70% using PCR. Identified types by DBH and PCR respectively were; HPV 6/11: 1% and 2%, HPV 16/18: 16% and 41%, and HPV 31/33/35: 7% and 14%. PCR detected unidentified types in 13%. Since PCR resulted in a 2.9 times higher HPV DNA detection rate, the choice of detection system has a major impact on the HPV status of cervical smears interpreted as CIN 1.

Thomas and Dembo argue that there are a few patients treated by radical hysterectomy for stage IB and 2A cervix cancer who would have an increased probability of cure if treated postoperatively by radiotherapy. We agree with the line in reasoning in this article, but believe the argument can be carried further. In our Institution, the major indication for primary surgical management of stage IB and 2A cervix cancer is to avoid the side-effects of radiation treatment, particularly in younger patients. The cure rates for patients with stage IB and 2A cervix cancer would appear to be the same, whether the patients are treated by radical radiotherapy or radical surgery, although pelvic control rates may be higher in patients treated by primary radiotherapy as discussed in the article. Radical surgery has the advantage of identifying a group of patients at high risk of having occult systemic disease. Regrettably, treatment for systemic metastases in this disease is rarely if ever curative at the present time. The morbidity rates in patients treated by radical surgery combined with radiotherapy are significantly higher than when either modality is used alone, and thus, combined surgery and radiation treatment should be avoided unless clearly indicated. It is our belief that the majority of patients who might be cured by the addition of radiotherapy to radical surgery can be identified by careful assessment before treatment is started. The size of the tumor and the extent of myocervix invasion can usually be gauged adequately by careful examination under anaesthetic by an experienced Gynecological Oncologist and Radiation Oncologist together. MRI scanning is probably the most useful imaging technique for determining the extent of cervical cancer prior to treatment 0). Very frequently, vascularlike space invasion can be detected by careful pathological review of adequate pretreatment biopsies, as can tumor grade. We recognize that sometimes patients will be referred for radiotherapy with the radical surgery already performed. In these circumstances, the suggested guidelines by Thomas & Dembo that are currently being studied by the G.O.G. in Protocol #92 would seem to be very appropriate. It is our belief, however, that these patients can usually be identified preoperatively and are better treated by radical radiotherapy, thus avoiding the increased morbidity of combined modality treatment. Further, we are concerned that the mere performing of a study such as G.O.G. Protocol ~92 may be perceived as adding legitimacy to operating on patients who would be better treated by radiotherapy alone, and risks a disservice to our patients.

Cisplatin-based combination chemotherapy is the current standard chemotherapy for the management of advanced stage, epithelial ovarian cancer. However, correlation has been demonstrated previously between dose intensity and response for cisplatin, but not for the other cytotoxic drugs commonly used. We treated 46 consecutive, newly diagnosed patients following standard debulking laparotomy with cisplatin 60 mg m-2 every 2 weeks for a total of 8 cycles. Survival and toxicity were compared with those of a similar cohort of 24 consecutive, newly diagnosed patients treated with cisplatin 75 mg m-2 plus cyclophosphamide 600 mg m-2 every 4 weeks for 6 cycles, at the same institution immediately prior to the current cohort. The single-agent cisplatin cohort received a mean relative cisplatin-equivalent dose intensity of 1.43 compared with a received mean relative cisplatin-equivalent dose intensity of 0.88 in the combination chemotherapy cohort, a 62.5% increase in the cisplatin dose intensity. At 2 years, 69% of the patients receiving single-agent cisplatin were alive, compared with 38% of the group receiving the combination chemotherapy (P = 0.014). Alopecia (P < 0.00001) and myelosuppression (P < 0.0000001) were markedly less in the patient group receiving single-agent cisplatin. There was no significant difference in the incidence of neurotoxicity (P = 0.28) or nephrotoxicity (P = 0.38) between the two patient groups. In summary, relatively dose intensive, single-agent cisplatin given in a biweekly schedule for the first-line management of advanced stage, ovarian cancer produced a survival advantage compared with the previous combination cyclophosphamide/platinum combination chemotherapy. This novel therapy takes one-third less time to complete and causes fewer side effects than the current standard of combination cyclophosphamide and cisplatin.