Surgery and prognosis in stage III epithelial ovarian cancer.

The results of this retrospective case study indicate that a composite of tumor grade, pattern of spread and substage at the time of opening affects the outcome most in the treatment of stage III epithelial tumors of the ovary. The poorest prognosis was associated with grade 3 histology, a pattern of spread requiring extensive and often difficult surgery for removal and a high substage. The best prognosis was usually associated with grade 1, with either very easily removed, isolated spread or low substage. The extent of tumor defined the degree of primary cytoreduction possible. If the tumor was minimally extensive, primary cytoreduction results were excellent. The same conclusions were reached in the case of secondary cytoreduction at the time of second-look procedure. There was no statistically significant difference (z = 1.481, P = 0.069) in 5-year survival between patients with microscopic only disease (59%) at second-look, and patients with gross disease not cytoreduced (36%).

Invasive cervical cancer following cryotherapy for cervical intraepithelial neoplasia or human papillomavirus infection.

OBJECTIVE: To determine the following: 1) the causes for the failure of cervical cryotherapy to prevent cervical cancer, and 2) whether cervical cryotherapy is associated with the development of cervical adenocarcinoma rather than squamous carcinoma. METHODS: We reviewed the medical charts of 327 women with cervical cancer. One hundred forty-seven for whom pertinent history was missing were contacted by telephone or at clinic visits. History obtained verbally was confirmed by outside medical records. Cervical biopsies (N = 16) and endocervical curettages (ECCs) (N = 15) performed before cryotherapy and biopsies at the diagnosis of cancer (N = 21) were reviewed. RESULTS: Twenty-one women with cervical cancer had a history of cryotherapy for cervical intraepithelial neoplasia (CIN) or human papillomavirus infection (HPV). The interval between cryotherapy and cancer was more than 2 years in 19 and more than 5 years in ten. Several categories of pre-treatment errors were identified. Evaluation before cryotherapy was appropriate in only nine cases. Interpretive errors were noted in three of 16 cervical biopsies and ten of 15 ECCs. After cryotherapy, 12% of women had appropriate follow-up. Of the invasive cancers that developed, 24% in the cryotherapy group and 21% in the non-cryotherapy group were adenocarcinomas. CONCLUSIONS: Careful evaluation before cryotherapy, accurate pathology reports, and consistent long-term follow-up are necessary if cryotherapy is to be used to treat CIN or HPV. We found no evidence that cryotherapy is associated with the development of cervical adenocarcinoma.

A randomized trial of three methods of obtaining Papanicolaou smears.

The relationship between technique of obtaining Papanicolaou smears, presence of endocervical cells, and rate of cervical neoplasia was studied by comparing an endocervical and ectocervical nylon brush (Bayne brush), Ayre spatula plus endocervical brush, and spatula plus cotton-tipped swab in a randomized, prospective trial involving 11,061 patients. Eligible patients had a cervix and were not pregnant. Clinic records of patients with abnormal cytology were reviewed to determine the pathologic diagnosis. Whether pathology was defined as including condyloma, dysplasia, and cancer; dysplasia and cancer; moderate dysplasia, severe dysplasia, and cancer; or just severe dysplasia and cancer, no significant difference was found in the rates of pathology between the three techniques. Endocervical cells were identified in 89.5% of smears obtained with the Bayne brush, in 91.5% with the spatula plus endocervical brush, and in 71.1% with the spatula plus cotton-tipped swab (P less than .001). Among smears obtained with the spatula plus swab, the rate of any pathology was higher in smears that contained endocervical cells than in smears in which endocervical cells were absent (2.0 versus 0.6%; P = .009). After correction for the influence of age, there remained predictive value with the presence of endocervical cells. Once corrected for the influence of age, the rate of pathology and abnormal cytology in smears obtained with the spatula plus brush or the Bayne brush was not dependent upon the presence of endocervical cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Presentation of cervical cancer.

To determine how patients with invasive cervical cancer present and whether presentation affects disease-free survival (DFS), a review of 81 patients treated for cervical cancer by the Division of Gynecologic Oncology and Pelvic Surgery at the Southern California Permanente Medical Group between January 1, 1986, and December 31, 1986, was performed. Fifty-six percent of patients presented with abnormal vaginal bleeding, twenty-eight percent presented with abnormal Papanicolaou (Pap) smears, nine percent presented with pain, four percent presented with vaginal discharge, and four percent presented with other symptoms. Follow-up was 24 to 41 months. Patients presenting with abnormal Pap smears had DFS of 96%. Those presenting with abnormal vaginal bleeding had DFS of 51% and those presenting with pain had DFS of 29%. Presentation strongly influences DFS (chi 2 = 16.8, P less than 0.001). Of women presenting with abnormal Pap smears, 87% were Stage I and 13% were Stage II. Of women presenting with other than abnormal Pap smears, 40% were Stage I, 34% were Stage II, and 26% were Stage III or IV. Presentation with abnormal Pap smear and stage are significantly related (chi 2 = 14.8, P less than 0.001). Of women presenting with abnormal Pap smears, 89% had cancers 0 to 2 cm, 5% had cancers 2.1 to 4 cm, and 5% had cancers greater than 4 cm in diameter. Of women presenting with other than abnormal Pap smears, 21% had cancers 0 to 2 cm, 26% had cancers 2.1 to 4 cm, and 53% had cancers greater than 4 cm in diameter. Presentation with abnormal Pap smear is significantly associated with tumor size (chi 2 = 25.4, P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Combined vesicovaginal-ureterovaginal fistulas associated with a vaginal foreign body.

A case is presented of vesicovaginal-ureterovaginal fistulas associated with a neglected vaginal foreign body. The patient complained of a foul-smelling vaginal discharge and was found to have a 4-cm hard vaginal mass on examination. Urinary incontinence developed subsequently. Examination under anesthesia was performed, and an aerosol deodorant cap was operatively removed from her posterior vagina/perirectal space. Subsequent work-up demonstrated the presence of both a vesicovaginal fistula and a right ureterovaginal fistula. The patient underwent a combined vaginal repair of the vesicovaginal fistula and abdominal ureteroneocystostomy. The frequency, types, etiology, and treatment of genitourinary fistulas are reviewed with particular attention to those associated with a vaginal foreign body.

Second-look procedures in ovarian cancer patients receiving six vs. nine courses of platinum, adriamycin, cytoxan (PAC) chemotherapy: the SCPMG experience 1982-1985.

From July 1, 1982, through December 31, 1985, 100 patients with Stage I, II, or III ovarian cancer, who were clinically NED following primary chemotherapy, underwent second look laparotomy. A prospective, nonrandomized study was set up among the various institutions within the Southern California Kaiser Permanente Medical Group. Those patients being treated at the Tertiary Oncology center received six courses of PAC while patients treated at other centers received nine courses of PAC. There was no selection as to severity of disease. Patients with Stage IV disease were not subjected to second-look procedures. Twenty patients with Stage I disease received other than PAC chemotherapy. Eighty patients with Stage II and III disease received PAC chemotherapy; 39 had six courses and 41, nine courses or more of PAC. Standard second-look procedure was performed and the status of the second-look procedure was the determining factor of response. Eighteen of the 39 patients (46%) who received six courses and 26 of 41 patients (63%) who received nine courses of chemotherapy had negative second-look procedures. Sixty-five patients had Stage III ovarian cancer, 34 with six courses of therapy and 31 with nine courses of therapy. There was no statistical difference in the incidence of positive or negative second-look procedures between the groups. The therapeutic index of six courses of PAC chemotherapy was in our hands, higher than with nine courses, since there was no observed difference in the status of the second-look and there was significantly more toxicity with the nine courses of therapy.

A comparison of the Papanicolaou smear and the cervigram: sensitivity, specificity, and cost analysis.

A total of 3271 gynecology patients between the ages of 18-50 years were screened for cervical intraepithelial neoplasia and invasive cervical cancer by simultaneous Papanicolaou smears and cervigram, a noninvasive photographic method recently introduced for screening. The accuracy of each screening test, when positive or suspicious, was evaluated independently and the results compared with colposcopically directed biopsy results. The cervigram was significantly more sensitive than the Papanicolaou smear (P less than .001), whereas the Papanicolaou smear was significantly more specific than the cervigram in detecting cervical intraepithelial neoplasia (P less than .001). Cost analysis integrating sensitivity and specificity with cost per procedure indicated a greater yield of cervical intraepithelial neoplasia with the cervigram than with the Papanicolaou smear, by 3.7:1 case per dollar.

Use of tracheloscopy and directed biopsy for evaluating cervical involvement in endometrial carcinoma.

Accurate assessment of cervical involvement in endometrial carcinoma (stage II) is often difficult. The value of tracheloscopy as a possible method for improving accuracy was assessed. One hundred one patients with endometrial carcinoma were studied; 28 were suspected of having cervical involvement on endocervical curettage, and 26 were evaluable. Only five patients were documented to have cervical involvement using tracheloscopy. This finding suggests that there is general overtreatment of patients with false-positive endocervical curettage. However, a definitive statement concerning the incidence of stage II disease in the series cannot be made because many patients received traditional preoperative radiation therapy, which may have eradicated intracervical disease missed by tracheloscopy, therefore falsely confirming stage 1 disease on history from subsequent hysterectomy specimens.

Fallopian tube adenocarcinoma: common extraperitoneal recurrence.

Fallopian tube adenocarcinoma is a rare gynecologic tumor that spreads like epithelial ovarian carcinoma. From 1954 to 1982, thirty patients with tubal adenocarcinomas were treated at UCLA and by the Southern California Permanente Medical Group. The mean age was 52 years. Pain, irregular or postmenopausal bleeding, and vaginal discharge were the most common presenting symptoms. Twenty-two had undergone previous pelvic or abdominal surgery. A pelvic mass was the most common physical finding, while Pap smears, IVP, and BE were rarely helpful in making the diagnosis or planning treatment. All of the patients in this report underwent primary therapeutic surgery. Nineteen patients received radiation and fourteen, systemic chemotherapy. Surgical stage was prognostic for survival. Fourteen patients with Stage I and II disease are NED (4 at 2 years; 10 at 5 years). No patients with Stage III or IV disease survived 5 years. Recurrences were noted as late as 6 years after primary therapy and 10 of 14 recurrent sites were extraperitoneal.

Multidrug treatment of advanced and recurrent endometrial carcinoma: a Gynecologic Oncology Group study.

Patients (358) with advanced (FIGO stages III and IV) or recurrent endometrial cancer were treated with one of two regimens: 1) melphalan and 5-fluorouracil daily for four days, repeated every four weeks with megace daily for eight weeks and 2) adriamycin, 5-fluorouracil, and cyclophosphamide, intravenous bolus every 21 days with megace daily for eight weeks. All patients were randomized except for 63 with known cardiac disease who were assigned to regimen 1 (to avoid adriamycin) and studied separately. Stratification was effected for performance status, history of previous progestational therapy, presence or absence of measurable disease, and stage of disease. The objective response rate in those with measurable disease was 36.8% in both groups; 36.8% of each group had stable disease, and only 26.4% progressed on treatment. Response was unaffected by site of recurrence, time to first recurrence, presence or absence of previous treatment by progestational or radiation therapy, or age. Grade of tumor and performance status did affect response, although 44 of 57 objective responders had undifferentiated tumors. The two combinations achieved response rapidly, required careful supervision, and were especially useful in treating patients with usually poor prognostic features.

Residual tumor following radiotherapy for locally advanced carcinomas of the uterine cervix. Prognostic significance.

Over a five-year period from 1977 to 1982, 120 patients with locally advanced carcinomas of the uterine cervix were surgically staged by lymphadenectomy and laparotomy. Radiotherapy was then administered according to the pelvic extent of disease, and all patients underwent extrafascial total hysterectomy with adnexectomy at ten weeks after completing radiation therapy. The presence or absence of residual tumor in the hysterectomy specimen appeared to be an important prognostic factor in treatment success or failure. Patients with no residual tumor were found to have an excellent prognosis. Those with residual tumor clear of the resection margins were at risk for distant metastases. Only one survivor was noted in the group of patients in whom the margins of resection were involved with tumor, nearly all of these patients dying from local recurrences. Major operative morbidity in the series was minimal, and consisted of a single ureterovaginal fistula, which required urinary diversion.

Ovarian carcinoma: management of stress in patients and physicians.

A discussion of the management of ovarian cancer invariably involves the problems of death and dying faced by the patient, her family, and her physician. This paper attempts to deal with the general fears, anxieties, and problems of terminality, and also places attention on specific issues involved in living with the ongoing disease and its treatments. Focus is on the effects of the disease on the woman's self-image, on her family and relationships, on life outside the hospital, and on her relationship with her attending physician. Specific problems relating to the periods of (1) diagnosis, (2) operative management and treatment, and (3) terminality are discussed. Understanding the psychosocial realities of the patient provides the physician with added insights into methods to assist the patient in adaptation and coping with this ultimately fatal disease.

The value of "routine tests" in the staging evaluation of gynecologic malignancies: a cost effectiveness analysis.

The value of tests employed in the clinical staging of patients with carcinomas of the cervix and endometrium has been examined in a retrospective review of 739 consecutive patients seen at Tufts-New England Medical Center. The yield of positive results of the barium enema (0%) and proctosigmoidoscopy (0.8%) in carcinoma of the cervix suggests that some of these studies may be omitted in asymptomatic patients with early disease on pelvic examinations. Similarly, for carcinoma of the endometrium, the yields from barium enema (0.9%) cytoscopy (0.9%) and proctosigmoidoscopy (0.6) are low. It is concluded that optimal patient care (with respect to morbidity and costs) may be provided without routinely performing these studies in staging asymptomatic patients with cervical and endometrial carcinomas.

Use of thyroid supplements in relation to the risk of breast cancer.

We conducted a case-control study to determine whether the use of thyroid supplements increases the risk of breast cancer. We compared 659 women with breast cancer and 1,719 control subjects. The rates of use of thyroid supplements were 9.1% and 8.7%, respectively (age-standardized rate ratio, 1.0; 95% confidence interval, 0.7 to 1.3). There was no evidence of an association when women known to be at increased risk for breast cancer (eg, nulliparae) were examined, even when thyroid supplements were taken for more than 15 years. Overall, there were no grounds to suggest that the long-term use of thyroid supplements increases the risk of breast cancer.

Decreased risk of endometrial cancer among oral-contraceptive users.

PIP: A case-control study was carried out to assess the effects of OC (oral contraceptive) usage on the risk of endometrial cancer. The cases were chosen from an ongoing case-control surveillance program at the Drug Epidemiology Unit of Boston University Medical Center. 154 women with a diagnosis of endometrial cancer were compared with 525 controls as to OC usage. 1% of the cases and 2% of the controls had used sequential OCs, numbers too small for inclusion in the study. 6% of the cases and 13% of the controls had used combination OCs. The relative risk of developing endometrial cancer was found to be only .5 for women who had used combination OCs. This halved risk rate falls to .3 for use that lasted for 3 or more years. There was no evidence that the time of last use affected the reduced risk factor; i.e., the reduced risk appeared to persist for at least 5 years after discontinuation of OC use. This protection against endometrial cancer offered by combined OC use may begin to show up in incidence rates for the disease soon if the protective effect does indeed remain after usage.^ieng

Recent and past use of conjugated estrogens in relation to adenocarcinoma of the endometrium.

It has been suggested that the reported association between estrogen use and endometrial cancer may have been biased because estrogens provoke uterine bleeding in women with otherwise asymptomatic disease. To evaluate this hypothesis we compared 149 patients with endometrial cancer and 402 control subjects with other conditions with reference to the time when they had last used conjugated estrogens. In women who had last used conjugated estrogens two or more years previously and who had taken them for at least five years, the rate-ratio estimate was 3.3 (95 per cent confidence interval, 1.4 to 8.0) relative to women who had never used them. Uterine bleeding, and hence the diagnosis of otherwise asymptomatic cancer, cannot be attributed to estrogen use that ceased in the distant past. Our results suggest that such use has a residual effect on the risk of endometrial cancer; this effect is not accounted for by biased selection of cases according to estrogen use.

Prognosis and treatment of endometrial cancer.

An understanding of the patterns of spread and prognostic factors influencing survival is necessary to develop rational treatment programs for patients with endometrial cancer. The most important risk factors include the stage of tumor, status of pelvic lymph nodes, depth of myometrial penetration, tumor grade, cell type, and patient age. Because of the inherent inaccuracies of staging based on pelvic examination and the inability to assess the status of lymph nodes or myometrial penetration clinically, errors in management often result when radiation therapy is delivered prior to operation. Therefore, a rationale is offered for primary operative management of patients with Stage I disease, with consideration of adjunctive radiation therapy following operation based on extend of disease and a thorough evaluation of the high-risk factors. It is suggested that patients with more advanced stages of disease be considered for pretreatment operative evaluation. Data are presented which refute theoretical objections to this approach.