Malignant eccrine spiradenoma of the vulva: a case report and review of the literature.

Malignant eccrine spiradenoma is a rare skin tumor of sweat gland origin. We present the first reported case of this tumor in the female genitalia. Due to the rarity of this tumor, there has yet to be an established standard of care. The present case is that of a 41-year-old woman with malignant eccrine spiradenoma of the periclitoral region. She had an 18-month history of a recurrent, painful mass adjacent to the clitoris. Her diagnosis was made after excision of the cystic tumor. The patient then underwent a partial radical vulvectomy with bilateral sentinel lymph node sampling. As malignant eccrine spiradenoma is a rare tumor, no standard care exists for treatment and postoperative management. Based on our review of the literature, wide local excision appears to be the preferred initial treatment. Furthermore, adjuvant chemotherapy and/or radiation does not seem to improve survival in patients with advanced or recurrent cancer. Although lymph node sampling and/or lymphadenectomy is frequently reported in the treatment of this tumor, hematogenous metastasis can also occur. Therefore, these patients require close postoperative follow-up for recurrent disease.

Surgical management of epithelial ovarian cancer: a review of the literature.

Epithelial ovarian cancer affects over 190,000 women worldwide. Over the past 40 years the median survival rate for women affected with this disease has increased from 12 months to 38 months. While advances in chemotherapy have enhanced our armamentarium, optimal cytoreductive surgery by well trained specialists offers the best opportunity for a long disease free interval.

HPV infection and number of lifetime sexual partners are strong predictors for 'natural' regression of CIN 2 and 3.

The aim of this paper was to evaluate the factors that predict regression of untreated CIN 2 and 3. A total of 93 patients with colposcopic persistent CIN 2 and 3 lesions after biopsy were followed for 6 months. Human papillomavirus (HPV) types were determined by polymerase chain reaction at enrolment. We analysed the biologic and demographic predictors of natural regression using univariate and multivariate methods. The overall regression rate was 52% (48 out of 93), including 58% (22 out of 38) of CIN 2 and 47% (26 out of 55) of CIN 3 lesions (P=0.31 for difference). Human papillomavirus was detected in 84% (78 out of 93) of patients. In univariate analysis, 80% (12 out of 15) of lesions without HPV regressed compared to 46% (36 out of 78) of lesions with HPV infection (P=0.016). Women without HPV and those who had a resolution of HPV had a four-fold higher chance of regression than those with persistent HPV (relative odds=3.5, 95% CI=1.4-8.6). Women with five or fewer lifetime sexual partners had higher rates of regression than women with more than five partners (P=0.003). In multivariate analysis, HPV status and number of sexual partners remained as significant independent predictors of regression. In conclusion, HPV status and number of lifetime sexual partners were strongly predictive of regression of untreated CIN 2 and 3.

A randomized, double blind, Phase III trial using oral beta-carotene supplementation for women with high-grade cervical intraepithelial neoplasia.

To evaluate the effect of daily beta-carotene (30 mg) versus placebo over a 2-year period on cervical intraepithelial neoplasia (CIN) 2 and 3 lesions. Human papillomavirus (HPV) typing was done to determine whether lesion regression was related to HPV. Micronutrient levels were measured to determine whether levels were predictive of regression. Variables that influence the risk of HPV infection and CIN, such as cigarette smoking and sexual behavior, were evaluated. Women were randomized to beta-carotene or placebo, with cytology and colposcopy every 3 months. Cervical biopsies were performed before treatment and after 6 and 24 months to evaluate response. Persistence of or progression to CIN 3 resulted in removal from the study, whereas treatment continued for 2 years on all others. The presence and type of HPV was determined by PCR. Response was defined as an improvement in CIN by 2 grades. Mantel-Haenszel chi(2) test was used to analyze response to treatment. Fisher's exact test was used to determine the effect of HPV and CIN grade on response Wilcoxon's rank-sum tests were used to compare micronutrient levels between groups. Twenty-one of 124 enrolled women were not randomized because they either moved, became pregnant, voluntarily withdrew, or the pathological review of their initial cervical biopsies did not confirm CIN 2 or 3. Of the remaining 103 women, 33 experienced lesion regression, 45 had persistent or progressive disease, and 25 women did not complete the study and were considered nonresponders in the final analysis. The overall regression rate (32%) was similar between treatment arms and when stratified for CIN grade. Data on 99 women with HPV typing showed that 77% were HPV-positive and 23% HPV-negative at enrollment. HPV-positive lesions were subdivided into indeterminate-, low-, and high-risk categories; the response rate was highest for women with no HPV detected (61%), lower for indeterminate/low-risk (30%), and lowest for high-risk (18%; P =.001). CIN regression was negatively correlated with retinol levels. In conclusion, beta-carotene does not enhance the regression of high-grade CIN, especially in HPV-positive subjects.

Vaginal hysterectomy as primary treatment of endometrial cancer in medically compromised women.

OBJECTIVE: To study the survival, rates and patterns of recurrence, and perioperative morbidity in medically compromised women with endometrial cancer treated by primary vaginal hysterectomy. METHODS: Fifty-one patients with endometrial cancer treated initially by vaginal hysterectomy between 1977 and 1999 were identified at the University of California, Irvine Medical Center and affiliated hospitals. Data were retrieved from hospital and office records. Statistical analysis, including Kaplan-Meier methods, was performed and the disease-specific survival rates were estimated. This study has 80% power to demonstrate a greater than 20% improvement in 5-year survival over historical controls. RESULTS: Fifty-one women with uterine carcinoma clinically confined to the uterus underwent primary vaginal hysterectomy with (n = 26) or without (n = 25) salpingo-oophorectomy. Eighty-four percent were obese with a body mass index greater than 27. Additional risk factors for surgical complications included hypertension (57%), diabetes mellitus (27%), and cardiovascular disease (18%). One-third of patients had three or more risk factors. Surgical morbidity included one episode of acute hemorrhage necessitating transfusion and abdominal exploration. Blood transfusions were given to four additional patients. There were no perioperative deaths. Five women recurred and expired at a median of 13 months (range 3--53 months) after surgery. The 3- and 5-year disease-specific survival rates were 91.4% and 88.0%, respectively. CONCLUSION: Vaginal hysterectomy for the initial treatment of early-stage endometrial cancer is associated with a high rate of cure and minimal morbidity. Thus, it may be considered a reasonable alternative to the abdominal approach in medically compromised women.

Primary invasive carcinoma of the vagina: treatment with interstitial brachytherapy.

BACKGROUND: Because primary carcinoma of the vagina comprises less than 2% of all gynecologic malignancies, the reported experience in the treatment of large numbers of patients is available only from a few major centers and most often encompasses a variety of differences in treatment selection and technique. The objective of this study was to assess the long term results of an interstitial iridium-192 afterloading implant technique using the Syed-Neblett dedicated vaginal plastic template. METHODS: Patients who were treated from 1976 to 1997 were examined retrospectively. RESULTS: Seventy-one patients underwent interstitial implantation with (n = 61 patients) or without external beam radiotherapy. The median age was 59 years (range, 16-86 years). Patients were staged according to the International Federation of Gynecology and Obstetrics system and included Stage I (n = 10 patients), Perez modification Stage IIA (n = 14 patients), Perez modification Stage IIB (n = 25 patients), Stage III (n = 15 patients), and Stage IV (n = 7 patients). Each implant delivered an approximately 20-gray (Gy) minimum tumor dose, with the total tumor dose reaching 80 Gy with integrated external beam radiotherapy. Local control was achieved in 53 patients (75%). The median follow-up was 66 months (range, 15-163 months), and the 2-year, 5-year, and 10-year actuarial disease free survival rates are 73%, 58%, and 58%, respectively. By stage, 5-year disease free survival rates included Stage I, 100% of patients; Stage IIA, 60% of patients; Stage IIB, 61% of patients; Stage III, 30% of patients; and Stage IV, 0% of patients. The factors disease stage and primary lesion size independently influenced the survival rates. Significant complications occurred in 9 patients (13%) and included necrosis (n = 4 patients), fistulae (n = 4 patients), and small bowel obstruction (n = 1 patient). CONCLUSIONS: Interstitial irradiation can effect local control in the majority of patients with primary carcinoma of the vagina with acceptable morbidity. Long term cure is demonstrable in patients with Stage I-III disease.

Intent-to-treat analysis of stage Ib and IIa cervical cancer in the United States: radiotherapy or surgery 1988-1995.

OBJECTIVE: To estimate the patterns of care and outcome of women with early cervical cancer in the United States based on surgical or radiation intent-to-treat principles. METHODS: The Surveillance, Epidemiology, and End Results 1995 public-use file was the data source. Subjects between the ages of 15 and 80 years at diagnosis who were treated for stage Ib or IIa cervical cancer were identified. The 1039 women who comprised the study group were stratified according to age at diagnosis (40 years or less, older than 40 years), primary treatment intent (surgery, radiotherapy), tumor size (4 cm or less, over 4 cm), registry site, and ethnicity. Survival analyses included 784 women who had at least 2 years of follow-up. RESULTS: There were 276 cancers (26.5%) over 4 cm, and 586 (56%) women were older than 40 years at diagnosis. There were 741 (71%) subjects in the surgical intent-to-treat group, and the remainder (298) were in the radiation intent-to-treat group. Kaplan-Meier analysis indicated a 5-year survival advantage for women with tumors 4 cm or less who were in the surgical intent-to-treat group compared with the radiation intent-to-treat group (86% and 71%, P <.001). Treatment group was not prognostic for cervical cancers over 4 cm (surgical intent-to-treat compared with radiation intent-to-treat; 72% and 68% survival, respectively). Multivariable analysis confirmed a survival advantage for women with surgical intent-to-treat and tumors of 4 cm or less. CONCLUSION: In the United States there is a survival advantage for surgical intent-to-treat compared with radiation intent-to-treat for women with tumors 4 cm or less, independent of ethnicity, adjuvant therapy, or age.

Tubal sterilization and risk of cancer of the endometrium.

OBJECTIVE: Surgical sterilization is a common method of contraception among U.S. women. Most surgical sterilizations are tubal ligations, but few studies have investigated their potential impact on endometrial cancer risk. METHODS: A case-control study included 405 women diagnosed with endometrial cancer at 5 U.S. medical centers between 1987 and 1990 and 297 age-, race-, and location-matched controls who were identified by random-digit-dialing. Questionnaires ascertained information on tubal sterilization, and logistic regression models generated odds ratios (ORs) to estimate relative risk. RESULTS: The OR and 95% confidence interval for tubal sterilization, which was reported by 47 cases and 40 controls, was 0.9 (0.6-1.4) before adjustment and 1. 4 (0.8-2.4) after adjustment for age, parity, and oral contraceptive use. Age at surgery, years since surgery, or calendar years of surgery were not associated with endometrial cancer, and associations did not vary according to parity or stage of disease at diagnosis. CONCLUSIONS: Tubal sterilization is not substantially associated with endometrial cancer.

Malignant germ cell tumors of the ovary.

OBJECTIVE: To evaluate the efficacy of adjuvant therapy for ovarian germ cell tumors. METHODS: We reviewed records of women who had malignant germ cell tumors of the ovary from 1977-1997. RESULTS: Seventy-two women had surgical resections of malignant ovarian germ cell tumors and most received adjuvant therapy. Fifty-six women (78%) presented with stage I disease, and 16 (22%) had more advanced disease. Tumor subtypes included dysgerminoma (n = 20), yolk sac tumor (n = 8), immature teratoma (n = 29) and mixed germ cell tumor (n = 15). Surgical management of the 56 with stage I disease consisted of total abdominal hysterectomy, bilateral salpingo-oophorectomy, and extensive surgical staging in ten women, whereas a conservative surgical approach, consisting of unilateral adnexectomy with or without comprehensive surgical staging, was adopted in later years (n = 46). Fifty-six women were treated with postoperative chemotherapy, predominantly platinum-based regimens. The 5-year actuarial survival rate was 93%. None of the 36 women who presented after 1984 have died of disease. CONCLUSION: These data confirmed that platinum-based adjuvant treatments allow most women with ovarian germ cell malignancies to have conservative surgery without compromising survival.

Interstitial brachytherapy for vaginal recurrences of endometrial carcinoma.

OBJECTIVE: The aim of this study was to evaluate the efficacy of interstitial brachytherapy in the management of vaginal recurrences of endometrial carcinoma. METHODS: Thirty patients received interstitial irradiation, with or without external beam radiotherapy. They were followed for a minimum of 5 years or until death. RESULTS: The median age was 66 years at initial diagnosis of endometrial cancer. FIGO stages included Stage I (n = 18), Stage II (n = 7), and Stage III (n = 5). All patients were treated originally by total abdominal hysterectomy and bilateral salpingo-oophorectomy, with or without lymphadenectomy, and 13 (43%) also received postoperative adjuvant whole pelvis radiotherapy as part of their primary treatment. Vaginal recurrences were diagnosed at a mean interval of 29 months after hysterectomy (range, 3-119 months). No patient had clinical evidence of pelvic sidewall extension or of distant metastatic disease. All patients were treated with interstitial brachytherapy; each implant delivered a mean maximal tumor dose of 25.5 Gy. Eighteen patients (60%) also received external beam radiotherapy (mean dose, 48 Gy) as part of their treatment for vaginal recurrence. Twenty-eight patients (93%) experienced a complete clinical response. Ten patients relapsed in the vagina (n = 5) or at distant sites (n = 5). Eleven patients are dead of disease. From the time of vaginal recurrence, the median overall survival was 60 months and the cause of death adjusted 5-year survival rate was 65%. Major morbidity included radiation proctitis (n = 2), fistula (n = 2), and radiation stricture (n = 1). CONCLUSION: Interstitial irradiation resulted in favorable local control as well as a 5-year survival rate and morbidity comparable to that reported previously for conventional brachytherapy.

Interstitial brachytherapy in the treatment of advanced and recurrent vulvar cancer.

OBJECTIVE: Our purpose was to evaluate the role of interstitial brachytherapy in vulvar cancer management. STUDY DESIGN: From 1985-1992 we performed a retrospective study of patients treated at the University of California, Irvine Medical Center, and Long Beach Memorial Medical Center. RESULTS: Eleven patients received interstitial brachytherapy, with (n = 5) or without (n = 6) external beam radiotherapy, for locally advanced (n = 5) or recurrent (n = 6) vulvar cancer. Local control was achieved in all patients. Ten patients have died of disease at a mean interval of 33 months from the time of treatment, with 9 patients having maintenance of local control at death. One patient is alive without disease after 77 months of follow-up. There were 2 cases of local necrosis (18%) and 1 case of rectovaginal fistula (9%). CONCLUSION: Local control of advanced vulvar cancer can be achieved with interstitial brachytherapy, with or without external beam radiotherapy. With improved systemic therapy this treatment modality may be used to salvage women with bulky, symptomatic tumors.

Management of ovarian cancer in patients older than 80 years of Age.

OBJECTIVE: The objective of this study was to examine the treatment, associated morbidity, and survival in very elderly patients with epithelial ovarian cancer. METHODS: A retrospective analysis of patients 80 years of age and older treated for epithelial ovarian cancer by the Gynecologic Oncology faculty at the University of California Irvine was performed. RESULTS: Eighteen patients were older than 80 years of age at the time of diagnosis of ovarian cancer. Median age was 83 years (range 80-86 years). There were 2 stage I, 10 stage IIIC, 4 stage VI, and 2 unstaged patients. One patient had a tumor of low malignant potential, 4 patients had grade II tumors, and 10 patients had tumors that were grade III. Eighty-three percent of patients had one or more preexisting medical illnesses. Cardiac disease, stroke, and hypertension were most common. Sixteen of 18 patients (88%) underwent primary debulking surgery. American Society of Anesthesiologists physical status classification was as follows: 7/16 (44%) class II, 6/16 (38%) class III, and 2/16 (13%) class IV. The procedures performed included 16 bilateral salpingo-oophorectomies, 11 total abdominal hysterectomies, 16 omentectomies, 3 lymph node dissections, and 7 bowel resections. Four (25%) patients were optimally cytoreduced to <1 cm of residual disease. Seventy-five percent of surgical patients received blood transfusions of 2 or more units PRBC. Mean EBL was 600 cc (range 200-4200 cc). Thirty-eight percent of patients experienced major postoperative morbidity. There were 7 patients with postoperative congestive heart failure, 3 with sepsis, 1 with aspiration pneumonia, and 2 postoperative deaths. Seventy-five percent of patients spent time in the intensive care unit. Median number of days was 3 (range 1-22 days). Mean postoperative stay was 8 days (range 6-57 days). Sixty-five percent of patients were discharged to home. The other patients were discharged to intermediate care facilities or nursing homes. Eighty-three percent of patients received chemotherapy. Of the 10 patients (63%) receiving adjuvant chemotherapy, the mean interval from surgery to initiation of therapy was 3 weeks (range 1-4 weeks). Overall median survival was 6 months (range 1-45 months). Median survival in patients with optimal debulking was 32.5 months (range 7-45 months) compared to 3.5 months (range 1-41 months) in patients suboptimally debulked. CONCLUSIONS: In patients older than 80 years of age who undergo debulking surgery for ovarian cancer, serious medical comorbidity and advanced ASA status are common. Despite aggressive surgical effort and frequent blood transfusions, optimal debulking to less than 1 cm is achieved in only 25% of patients. Impressive morbidity and mortality occurs in this group of patients, but most patients are discharged to home and are able to receive postoperative chemotherapy.

Pregnancy in a Jehovah's witness with cervical cancer and anemia.

A 34-year-old Jehovah's Witness presented with vaginal bleeding and anemia at 23 weeks gestation. She was diagnosed with a FIGO Stage IB2 squamous cell carcinoma of the cervix. The patient refused transfusion of blood products and strongly desired to continue the pregnancy. She was hospitalized and at 33 weeks gestation underwent a Cesarean-radical hysterectomy with measures that minimized blood loss.

Radical hysterectomy with the endoscopic stapler.

OBJECTIVE: Morbidity associated with radical hysterectomy is significant. Utilizing the endoscopic stapler for transection of the cardinal ligaments and uterosacral ligaments is a possible method to decrease operative time and blood loss. METHODS: Two groups of patients, one group with the stapler used (n = 21) and the other with the traditional method utilized (n = 18), were compared in regard to operative and postoperative morbidity, operative time, and surgical margins. The groups were similar in regard to medical condition, age, and weight. RESULTS: Median (243 min versus 284 min) and mean (246 min versus 287 min) operative times were significantly less in the stapler group than in the control group (P < 0.002). Median blood loss was reduced by 20% in the stapler group (400 ml versus 500 ml, P < 0.03). There was no significant difference in febrile morbidity, surgical complications, or length of hospital stay. CONCLUSION: Our data suggest significant reduction in blood loss and operative time with the use of the endoscopic stapler.

Neuroendocrine small cell uterine cervix cancer in pregnancy: long-term survival following combined therapy.

A 22-year-old woman carrying twin gestations at 30 weeks presented with preterm labor and a prolapsing cervical mass. Following Cesarean section birth, she was treated with multiagent chemotherapy followed by pelvic radiotherapy for a Stage IIA small cell cancer of the uterine cervix. She is without evidence of disease 5.5 years after diagnosis and is the first reported long-term survivor of a small cell cervical carcinoma diagnosed during pregnancy.

Cervical cancer with paraaortic metastases: significance of residual paraaortic disease after surgical staging.

Cervical carcinoma frequently metastasizes to the paraaortic region, necessitating extended field radiotherapy to effect a cure. As imaging modalities are unreliable in identifying all cases of paraaortic nodal metastases (PAN), surgical staging is often utilized prior to radiotherapy. This study was aimed at identifying factors predictive of survival in women with cervical carcinoma and paraaortic metastases. In particular, survival based on extent of paraaortic disease was examined. The study group consisted of 43 women (stages IB-IVB) identified between 1982 and 1993 who were treated with extended field radiation for cervical carcinoma with histologically confirmed paraaortic metastases. The estimated 5-year survival for the study population was 24% with a median survival of 18 months. Pelvic tumor size had a significant impact on survival with the median survival being 34 months if the primary lesion was < 6 cm compared to 14 months if > or = 6 cm (P = 0.01). Eight of the 26 (31%) women without residual PAN disease after surgical staging remain alive and disease free (mean follow-up, 74 months). In contrast, only 1 of the 17 (6%) women with gross residual PAN is alive 71 months after treatment (P = 0.05). However, a comparison of Kaplan-Meier survival curves did not show a statistically significant advantage to the surgical excision of grossly involved PAN (P = 0.98). Although long-term survival among women with grossly involved, unresected paraaortic metastases is uncommon, further study is necessary to elucidate the role of surgical excision of bulky aortic disease in women with cervical cancer.

Evidence for a common etiology for endometrial carcinomas and malignant mixed mullerian tumors.

OBJECTIVE: To elucidate factors linked to the development of malignant mixed mullerian tumors (MMMT) and determine whether the risk factor profile for these tumors corresponds with that for the more common endometrial carcinomas. METHODS: A multicenter case-control study of 424 women diagnosed with endometrial carcinoma, 29 women diagnosed with MMMT, and 320 community controls was conducted. Review of pathological reports and slides was performed to classify cases by histological type. All participants were asked to respond to a questionnaire which ascertained information on exposure to factors postulated to be linked to the development of uterine tumors. RESULTS: Women with endometrial carcinomas and MMMTs were similar with respect to age and educational attainment. Women diagnosed with MMMTs were more likely than those diagnosed with carcinomas to be of African-American descent (28% vs 4%; P = 0.001). Weight, exogenous estrogen use, and nulliparity were related to risk of both tumor types. Marked obesity was associated with a 4.8-fold (95% CI = 3.0,7.6) increase in risk of carcinoma and a 3.2-fold (95% CI = 1.1,9.1) increase in risk of MMMT development. Use of exogenous estrogens increased the odds of developing carcinomas by 2-fold (95% CI = 1.3,3.2) and that of developing MMMTs by 1.8-fold (95% CI = 0.57,5.5). Nulliparity was associated with a 2.9-fold (95% CI = 1.9,4.8) increase in risk of carcinomas and a 1.7-fold (95% CI = 0.53,5.6) increase in risk of MMMTs. Oral contraceptive use protected against the development of both carcinomas (OR = 0.39; 95% CI = 0.26,0.58) and MMMTs (OR = 0.76; 95% CI = 0.25,2.3). Current smokers were at a reduced risk of developing endometrial carcinomas (OR = 0.34; 95% CI = 0.21,0.55) and MMMTs (OR = 0.57; 95% CI = 0.15,2.3), while former smokers were at an increased risk of MMMT (OR = 2.7; 95% CI = 1.1,6.8) but not carcinoma development (OR = 0.81; 95% CI = 0.56,1.2). CONCLUSION: Results from this study suggest that MMMTs and carcinomas have a similar risk factor profile. This observation is compatible with the hypothesis that the pathogenesis of these two histological types of uterine tumors is similar.

Analysis of histopathological features of endometrioid uterine carcinomas and epidemiologic risk factors.

A large case-control study was performed to determine whether risk factors for endometrioid carcinoma, the most common type of endometrial cancer, vary according to the histological features of the tumor. Study subjects consisted of 328 women with newly diagnosed endometrioid adenocarcinoma and 320 population-based control subjects. Variables studied included age at menarche, menopausal estrogen use, weight, parity, cigarette smoking, and oral contraceptive use. The risk factor profile for endometrioid carcinomas with and without squamous differentiation was very similar. No striking differences in risk factors were observed between endometrioid cancers with and without adjacent endometrial hyperplasia. Finally, none of the risk factors varied substantially between early-stage and late-stage tumors or low-grade and high-grade tumors. In summary, this study indicates that risk factors for endometrioid carcinomas are not related to the morphological features of the tumor.

Risk factors and hormone levels in patients with serous and endometrioid uterine carcinomas.

We performed a multi-institutional, incident case-control study of 328 endometrioid and 26 serous carcinomas to assess whether risk factors and circulating hormone levels in women with serous carcinoma differ from the expected profile for endometrial carcinoma We also evaluated exposures potentially related to endometrial cancer risk, anthropometric measurements, and circulating levels of sex hormones and related carrier proteins. Histopathologic specimens were reviewed without knowledge of the other data. As expected, a statistically significant association was observed for high body mass index (BMI) (relative risk, 3.5) and use of menopausal estrogens (relative risk, 2.4) in the endometrioid carcinoma cases, whereas serous carcinomas were not strongly associated with these factors. Smoking and oral contraceptive use decreased risk for both tumor types. For five of six sex hormones tested, age-adjusted mean serum levels in patients with serous carcinoma were significantly lower than those in women with endometrioid carcinoma. After adjustment for BMI, these differences were narrowed, but levels of albumin-bound estradiol and estrone remained significantly lower in the serous cases. Age and BMI-adjusted levels of sex hormone-binding globulin were significantly higher in patients with serous carcinoma than in women with endometrioid carcinomas. In conclusion, risk factors and sex hormone levels in patients with uterine serous carcinoma seem to differ from those in women with endometrioid carcinoma, suggesting that there may be at least two different pathways of endometrial carcinogenesis.

Colposcopic regression patterns in high-grade cervical intraepithelial neoplasia.

OBJECTIVE: To evaluate the serial changes in colposcopic and cervicographic findings of women with cervical intraepithelial neoplasia (CIN) II and III enrolled in a phase III randomized comparison of oral beta carotene and placebo. METHODS: All subjects treated with beta carotene or placebo for at least 6 months were included if they met the criteria of persistent or progressive disease (no change or worsening of CIN grade) or disease regression (improvement of two grades or more). These two groups were compared for changes in colposcopic and cervicographic patterns. Colposcopically directed biopsies and cervicography were done at enrollment and after 6 months. Quarterly Papanicolaou smears and colposcopic assessments also were performed. Findings of mosaic pattern, punctation, and white epithelium were graded and diagrammed at colposcopic examinations. Cervicographic measurements of the centripetal movement of metaplastic epithelium were recorded. Data were analyzed by chi 2 analysis and Fisher exact tests. RESULTS: Data were available for 23 subjects with regression and 16 with persistent lesions. Small lesions were significantly more likely to regress than large ones. Lesions without coarse punctation were significantly more likely to regress than lesions with coarse punctation, and lesions with mild acetowhite changes were more likely to regress than those with dense white epithelium. A pattern of centripetal movement of the metaplastic epithelium toward the cervical os was noted in lesions that regressed, but not in those that persisted or progressed. CONCLUSION: This study describes the centripetal growth of metaplastic squamous epithelium associated with the regression of CIN II and III. This observation contributes to our understanding of the process of disease regression in CIN and may be useful in identifying individuals for conservative management. Failure to identify this pattern correlates with persistent or progressive disease.