Early cervical cancer and parametrial involvement: is it significant?

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 II 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.

Histologic and clinical significance of atypical glandular cells on pap smears.

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.

Postoperative chemotherapy in advanced ovarian granulosa cell tumors.

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.

The natural history of CIN I lesions.

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

Predictors of co-incidental CIN II/III amongst a cohort of women with CIN I detected by a screening Pap test.

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 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 (

The HPV determinants of CIN I.

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 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.

Good outcome associated with a standardized treatment protocol using selective postoperative radiation in patients with clinical stage I adenocarcinoma of the endometrium.

In 1982, a treatment protocol was instituted for the management of patients with clinical stage I adenocarcinoma of the endometrium. All pertinent historical, operative, and pathologic findings were reviewed by a multidisciplinary committee and 384 patients were prospectively assigned to either high- or low-risk categories. Patients were excluded from the study if they had clinically apparent extrauterine disease, clear cell or serous histologies, or microscopic ovarian metastasis. Patients were considered high-risk if they had one or more of the following factors: grade 3 tumor differentiation, myometrial invasion > 50% of the total wall thickness, pathologic cervical involvement, or adenosquamous histology. Two-hundred twenty-seven (59%) low-risk patients were followed without further treatment after surgery, while pelvic radiation was recommended for 157 (41%) high-risk patients. The 5-year relapse-free survival rates in the low- and high-risk groups were 95 and 81%, respectively. There were no treatment-related deaths. Severe or life threatening chronic radiotherapy complications occurred in 6 (5%) patients. Multivariate Cox analysis identified the following significant prognostic factors: grade, myometrial invasion, cervix involvement, and age. This treatment protocol represents a safe and effective method of managing patients with carcinoma of the endometrium and spares the need for radiation therapy in the low-risk patient.

A paired comparison of dot blot hybridization and PCR amplification for HPV testing of cervical scrapes interpreted as CIN 1.

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.

Novel, dose intensive, single-agent cisplatin in the first-line management of advanced stage ovarian cancer.

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.