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Biomedical subjects

G C Stuart

Publications and source records attributed to G C Stuart.

At least 19 recordsLinked to original sources
PubMed1999

Intergroup collaboration in ovarian cancer: a giant step forward.

The rather slow evolution of so-called "optimal chemotherapy" for ovarian cancer is the result of suboptimal randomised clinical trials, not having the statistical power to identify truly superior regimens, and of the lack of systematic comparisons of new agents with relevant control arms. There is little doubt that we need international collaboration to move the field forward in a timely and coherent manner. European and transatlantic collaboration represents the beginning of the process and point to the success that can await us if the drive to work together remains strong. A similar organisation as for breast cancer (Breast International Group, BIG) needs to be established for ovarian cancer.

Clinical Trials as Topic↗
PubMed1998

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 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.

Adult↗
PubMed1998

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 </= 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.

Adolescent↗
PubMed1997

Review of the screening history of Alberta women with invasive cervical cancer.

OBJECTIVE: To conduct a failure analysis of cervical cancer screening among women with invasive cervical cancer in Alberta. DESIGN: Descriptive study. Review of demographic, staging and treatment information from cancer registry records; generation of documented screening history from Alberta Health billing records and self-reported history from subjects who agreed to be interviewed; and comparison of findings in initial cytology reports with those from subsequent review by at least 2 pathologists of all cytology slides for each patient for the 5 years before diagnosis. Cases were assigned to 1 of 6 categories of identified screening failure. SETTING: Alberta. SUBJECTS: All women with diagnosis of invasive cervical cancer reported to a population-based provincial cancer registry from January 1990 to December 1991. OUTCOME MEASURES: Demographic, staging and treatment information; documented and self-reported screening histories; correlation of test results in initial cytology report with those generated from slide review; category of identified screening failure. RESULTS: Of the 246 women identified with invasive cancer of the cervix, 37 (15.0%) had stage IA disease; 195 (79.3%) had squamous-cell carcinoma, and 35 (14.2%) had adenocarcinoma. According to the categories of screening failure, 74 women (30.1%) had never been screened, 38 (15.4% had not been screened within 3 years before diagnosis, 42 (17.1%) had had a false-negative cytology result, and 20 (8.1%) had been managed outside of conventional protocols. Of the 23 women (9.3%) who had been screened appropriately and had true-negative results, 19 had smears that were considered technically limited. It was not possible to classify 49 (19.9%) of the cases. Agreement between the documented and the self-reported screening histories was exact for only 39 (36.1%) of the 108 women interviewed. CONCLUSIONS: Despite widespread use of opportunistic cervical screening, many women in Alberta are still not being screened adequately. In most cases women are being screened too infrequently or not at all. Self-reported screening histories are unreliable because many women may overestimate the number of smears. An organized approach to screening, as recommended by the National Workshop in Cervical Cancer Screening, may assist in reducing the incidence of invasive cervical cancer.

Adenocarcinoma↗
PubMed1997

Risk-specific follow-up for endometrial carcinoma patients.

OBJECTIVE: To propose a risk-specific follow-up protocol for endometrial carcinoma patients. METHODS: A retrospective cohort of endometrial carcinoma patients was used to identify risk factors for recurrence. Based on a profile of risk factors, women were classified at either low or high risk for recurrence (median follow-up 70 months). The classification system was validated on a subsequent cohort. RESULTS: Surgical stage, grade, and histology were found to be significant predictors (P < 0.001) of recurrence. In the original cohort, patients with stage Ia, grade 1 or 2, or stage Ib, grade 1 adenocarcinoma, had a recurrence rate of 4/98 (4.1%). The remaining high-risk patients had a recurrence rate of 37/158 (23.4%). When applied to the subsequent cohort, the rates were similar: low risk 3/113 (2.7%) and high risk 30/140 (21.4%). Seventy-five percent of recurrences occurred within 3 years of diagnosis and the majority were heralded by site-specific symptoms. CONCLUSIONS: Women with endometrial carcinoma can be successfully classified for low or high risk of recurrence. It is proposed that low-risk patients not be maintained on routine follow-up and that a tailored schedule of follow-up be used for high-risk patients. These changes would serve patients more appropriately and use health care resources more efficiently.

Adenocarcinoma↗
PubMed1997

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 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.

Adolescent↗
PubMed1996

Spontaneous rupture of the urinary bladder: a late complication of radiotherapy--case report and review of the literature.

The spontaneous intraperitoneal rupture of the urinary bladder is an extremely rare life-threatening event. There are often difficulties in establishing the diagnosis. A patient with spontaneous perforation of the urinary bladder, 15 years after pelvic radiotherapy for carcinoma of the cervix is reported. Aspects of etiology, clinical presentation, diagnosis, and management are described. Special emphasis is placed on surgical management as it relates to long-term outcome.

Adult↗
PubMed1995

Phase II study to evaluate the toxicity and efficacy of concurrent cisplatin and radiation therapy in the treatment of patients with locally advanced squamous cell carcinoma of the cervix.

Sixty patients presenting with poor prognosis squamous cell cancer of the cervix have been studied in a phase II clinical trial. Patients were treated with radiotherapy and concurrent cisplatin chemotherapy every 10 days. Treatment was well tolerated with all patients completing radiotherapy as prescribed. There was one case of grade 4 acute bowel toxicity. Significant late morbidity was acceptable for this group of patients being restricted to two cases (3.3%) of grade 4 toxicity to the bowel. Pelvic control rates of 78% have been observed. There have been no pelvic recurrences after 26 months, although recurrences beyond the pelvis have occurred up to 4 years later. Actuarial 4-year survival is encouraging at 60%.

Actuarial Analysis↗
PubMed1995

The human papillomavirus status of invasive cervical adenocarcinoma: a clinicopathological and outcome analysis.

Accumulating evidence highlights the human papillomavirus (HPV) as a risk factor for cervical adenocarcinoma. However, the part played by the HPV in predicting tumor outcome or the increasing frequency of cervical adenocarcinoma is incompletely studied. In a retrospective study the association between HPV status and the clinicopathological characteristics of 77 cases of cervical adenocarcinoma was investigated. The data were then analyzed for temporal differences in HPV status and to identify outcome predictors. Human papillomavirus status was determined by dot blot hybridization using probes for HPV 6, 11, 16, 18, 31, 33, and 35, followed by polymerase chain reaction amplification of the dot blot negative cases. Seven type-specific and consensus HPV primers were used. Human papillomavirus type 16, 18, or 33 was present in 53 (70%) cases. Human papillomavirus status did not correlate with disease outcome or any clinicopathological variable, except that tumors presenting in and after 1981 were more frequently HPV positive than those presenting before 1981 (P = .014). In a multivariate analysis only clinical stage at presentation was predictive of disease outcome. Because temporal differences in clinicopathological characteristics were not identified, the increasing frequency of cervical adenocarcinoma may relate to a more important oncogenic role for the HPV in tumors presenting after 1980.

Adenocarcinoma↗
PubMed1995

Uterine atypical polypoid adenomyoma and ovarian endometrioid carcinoma: metastatic disease or dual primaries?

Atypical polypoid adenomyoma (APA) is an uncommon uterine tumor that rarely metastasizes, although it closely resembles a well-differentiated endometrioid carcinoma. A 37-year-old woman with a history of pelvic endometriosis and oral contraceptive use developed an APA and later presented with bilateral ovarian endometrioid carcinomas. DNA ploidy analysis and human papilloma virus (HPV) typing of the APA and ovarian carcinomas were performed to characterize the primary or metastatic nature of the tumors. Both tumors were aneuploid. The APA had a DNA index of 1.53, compared with 1.19 for the ovarian carcinoma. The APA contained HPV 18, and the ovarian carcinoma a mixed infection of HPV 6, 11, 16, and 18, with types 6 and 11 predominating. These differences in DNA index and HPV type supported the autonomous nature of the APA and the ovarian carcinomas. The report affirms the benign outcome of APA, highlights its complication by a second malignancy, and suggests an etiological role for endometriosis, steroid hormones, and possibly the HPV in the formation of one or both tumors.

Adenomyoma↗
PubMed1994

Carcinoma of the cervix following conservative management of cervical intraepithelial neoplasia.

The purpose of this study was to identify the reasons for treatment failures in patients managed with cervical intraepithelial neoplasia who subsequently developed invasive carcinoma of the cervix. Of 672 patients seen with cervical carcinoma from 1980 to 1990 inclusive, at the Tom Baker Cancer Centre, 24 (3.6%) had previously undergone conservative treatment for CIN and represent the current study population. The initial colposcopic-guided biopsy showed metaplasia (2), CIN 2 (5), and CIN 3 (17). The conservative treatment methods included observation (5), electrocautery (1), laser ablation (3), surgical cone (5), and cryotherapy (10). The mean time interval in months from conservative treatment of CIN to diagnosis of cervical cancer was 21.8 with cryotherapy and 26.7 with laser ablation. The FIGO stage of invasive cervical cancer was Stage 1A (7), Stage 1B (15), Stage 2A (1), and Stage 3 (1). The single death was a patient aged 30 with metastatic small cell cervical carcinoma arising within 4 years of cryotherapy for CIN 3. Of the 24 patients, 13 were managed appropriately yet developed carcinoma, 3 deviated from an accepted standard colposcopy protocol, 5 had inadequate follow-up, 2 refused treatment, and 1 developed de novo disease. The principle reason for treatment failure according to the literature is blatant deviation from protocol. This study, however, suggests that established invasive disease may have gone undetected prior to an ablative therapy. Difficulties related to diagnosis are discussed. The importance of peer reviews becomes evident if practices are to be evaluated and changes to protocols are to be implemented.

Adult↗
PubMed1994

An evaluation of routine follow-up of patients treated for endometrial carcinoma.

This retrospective review evaluates the outcome benefit of a standard follow-up protocol for 435 patients treated for endometrial carcinoma between 1981 and 1986. Routine follow-ups consisting of physical examinations and vaginal cytologies were done every 3 months for the first year, 4 months for the second year, and 6 months thereafter. Chest X rays were done biannually. Demographic, histopathologic, therapeutic, and follow-up data were studied. Exclusions due to incomplete follow-up (70), persistent disease (40), or other primary malignancies (8) left 317 patients with a disease-free state assigned to follow-up. Recurrences developed in 53 patients being followed, 40 (75%) of whom were symptomatic. Family physicians primarily diagnosed recurrences in 34 patients while recurrences in only 11 of the 53 patients (21%) were detected on routine follow-up at the cancer center (5 by examination and 6 by chest X ray). Therefore, only one recurrence was detected for every 206 routine follow-up visits. Vaginal vault cytology was not diagnostic in any patient. Seventy percent of recurrences occurred within 3 years. There was no statistical difference in survival between the group detected on routine follow-up and those who were symptomatic (P = 0.55). Routine follow-up of patients treated for endometrial cancer did not improve detection of recurrences or survival.

Endometrial Neoplasms↗
PubMed1994

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.

Cervix Uteri↗
PubMed1994

Adenocarcinoma in situ of the endocervix: human papillomavirus determination by dot blot hybridization and polymerase chain reaction amplification.

The frequency of human papillomavirus (HPV) in series of endocervical adenocarcinoma in situ (AIS) ranges from 6 to 100%. Some of this variability can be attributed to small study numbers and such technical considerations as the sensitivity of the hybridization method employed. Consequently, the role of the HPV in AIS oncogenesis is unclear. The frequency and relative distribution of HPV DNA types 6, 11, 16, 18, 31, 33, and 35 in 37 cases of AIS were determined and correlated with clinical variables. All cases were first typed by dot blot hybridization (DBH), and those found to be HPV negative were subsequently typed by polymerase chain reaction amplification with DBH enhancement (PCR/DBH). The HPV DNA positivity rate was 27% by DBH alone and 52% by PCR/DBH amplification. Combining the results of both methods, the overall HPV positivity rate was 66%: HPV 18 in 15 cases (43%), HPV 16 in eight cases (23%). The HPV status did not correlate with any clinical variable. This study showed that the sensitivity of the hybridization method is principally accountable for the variable frequency of HPV in AIS. The identification of only high-risk oncogenic HPV types in two-thirds of the cases suggests a significant role for the virus in AIS oncogenesis; HPV status, however, does not delineate a clinical profile.

Adenocarcinoma↗
PubMed1993

Intraperitoneal interferon in the management of malignant ascites.

BACKGROUND: Ascites secondary to malignancy is a major cause of recurring morbidity in patients with ovarian cancer. In patients previously treated with cisplatin, other chemotherapeutic agents are not likely to be effective in relieving symptoms. METHODS: A pilot group of ten patients was treated with intraperitoneal alpha-2B-interferon (alpha-2B-IFN) in an effort to provide symptomatic relief of their ascites. All patients had advanced epithelial ovarian cancer at the time of therapy and were receiving treatment for palliation only. Symptoms included abdominal distention (100% of patients), nausea and vomiting in the absence of mechanical intestinal obstruction (60%), and dyspepsia (40%). RESULTS: At a dose of 10 M units/m2 given intraperitoneally every 2 weeks for one to four treatments, the toxicity was low, but the benefits were minimal. Five (50%) patients reported symptomatic improvement of 2-7 weeks' duration. The most common side effects included fever (temperature of more than 38.5 degrees C) and abdominal pain. CONCLUSIONS: At the dose of 10 M units/m2 of intraperitoneal alpha-2B-IFN, this regimen did not appear to produce clinically significant palliation of the ascites in most patients.

Adult↗
PubMed1993

The human papillomavirus status of 114 endocervical adenocarcinoma cases by dot blot hybridization.

The reported rate of human papillomavirus (HPV) positivity in cases of endocervical adenocarcinoma averages 38% (range, 0% to 100%) and, in contrast to cervical squamous cell carcinoma, HPV type 18 rather than type 16 is the predominant type. The HPV positivity rate and distribution of types (status) in 114 endocervical adenocarcinoma cases (37 in situ and 77 invasive) were determined by dot blot hybridization using biotinylated probes to HPV types 6, 11, 16, 18, 31, 33, and 35. Human papillomavirus DNA was present in 27% of in situ and in 44% of invasive adenocarcinomas, and in nearly all histologic subtypes of invasive adenocarcinoma. Human papillomavirus status was not predictive of tumor grade, volume, depth of invasion, lymph-vascular space involvement, age at presentation, or year of diagnosis. Type of HPV might influence the histologic subtype of invasive adenocarcinoma, as HPV type 16 predominated in the adenosquamous carcinomas while HPV type 18 was more frequently found in all other subtypes. Since only types 16, 18, and 33 were identified, an oncogenic role for HPV in endocervical carcinogenesis was supported.

Adenocarcinoma↗
PubMed1993

Estrogen and progesterone receptor, human papillomavirus, and DNA ploidy analysis in invasive carcinoma of the cervix in pregnancy.

From 1980 to 1991, 13 patients had pregnancy-associated invasive carcinoma of the cervix: four carcinomas were stage IA; eight were stage IB; and one was stage IVB. Gestational ages range from 8 weeks to 3 months postpartum. Two patients are dead of disease and a third is alive with metastases. Results of immunoenzyme studies for estrogen receptors (ER) were variably positive in all except one tumor, whereas results of studies for progesterone receptors (PR) were uniformly negative. Thus, these hormone receptor studies are unlikely to be of prognostic significance. Six tumors contained human papillomavirus (HPV) DNA by in situ or dot blot hybridization (three, HPV 16; two, HPV 18; one, HPV 31/33/35). Thus, neither ER nor PR expression appears to be related to the infecting HPV type. Using flow cytometry, three tumors were determined to be aneuploid and a fourth, tetraploid. To correlate HPV or DNA flow cytometry data with prognosis will require study of larger numbers of patients from multiple centres.

Carcinoma↗