Evaluation of a cervical cytology device (cell-sweep) based on comparison to colposcopic findings.

A new cytology sampling device, the CellSweep, identifies squamous intraepithelial lesions with a sensitivity of 75%. The purpose of this study was to evaluate the accuracy of cervical cytology using a new sampling device combining an endocervical brush and ectocervical spatula into one unit (CellSweep, patented by R. Mohajer, Troy, Michigan). From April 1995 to July 1995, 71 patients referred to the Allegheny University Hospitals Colposcopy Clinic had cervical cytology obtained with the CellSweep and underwent colposcopic evaluation of the cervix. The ability of the CellSweep to detect an abnormality confirmed by colposcopic evaluation was studied. Colposcopically directed ectocervical biopsies were obtained only in patients with identifiable lesions (n = 32). No random biopsies were obtained. The cytology smear was unsatisfactory for interpretation in one case. The remaining 70 Papanicolaou smears were read as normal in 17 (24%) cases and atypical squamous cells in 19 (27%). A squamous intraepithelial lesion (SIL) was detected in 34 (48%) smears. The colposcopic evaluation was normal in 50 patients who had satisfactory Papanicolaou smears, whereas SIL was detected in 20 cases. In 31 patients, SIL was not present in either colposcopy or cytology. In this preliminary study, the CellSweep identified SIL with a sensitivity of 75% and a specificity of 62%. The CellSweep, which combines an endocervical brush and an ectocervical spatula into a single unit, seems to be an acceptable device for obtaining cervical cells for cytologic screening.

The significance of thrombocytosis in patients with locally advanced cervical carcinoma: a Gynecologic Oncology Group study.

OBJECTIVE: The aim of this study was to determine the incidence of thrombocytosis and its possible impact on survival probability among women with locally advanced cervical carcinoma. METHODS: The database of 294 patients with Stages IIB-IVA cervical carcinoma without periaortic node metastasis who were treated with standardized radiation therapy and concurrent hydroxyurea or misonidazole was analyzed. Pretreatment platelet counts were available for 291 patients who are the subject of this study. RESULTS: Thrombocytosis (platelet count >400 x 10(9)/liter) was present in 86 (29.6%) of the 291 patients. A multivariate Cox proportional hazards model showed that patients without extrapelvic disease and with thrombocytosis had a 55% greater chance of dying than those without thrombocytosis (relative risk = 1.55, 95% confidence interval 1.08-2.21). Patients with thrombocytosis had larger tumors and more frequently had bilateral parametrial involvement, tumor fixation to the sidewall, and positive pelvic lymph nodes than patients without thrombocytosis. Thrombocytosis was not found to be a prognostic factor in patients with positive pelvic nodes. However, in patients with negative pelvic nodes, the presence or absence of thrombocytosis was related to survival. CONCLUSION: Thrombocytosis is a frequent finding among patients with advanced cervical carcinoma and seems to be related to tumor burden. Among patients with locally advanced cervical carcinoma who had negative pelvic nodes, those with thrombocytosis had a poorer survival.

Clinical significance of a cytologic diagnosis of atypical glandular cells of undetermined significance.

OBJECTIVE: To assess the clinical significance of a cytologic diagnosis of atypical glandular cells of undetermined significance (AGUS) and determine the most appropriate evaluation of these patients. STUDY DESIGN: Between 1993 and 1995, 44,217 Papanicolaou smears were evaluated at Allegheny University Hospitals, Medical College of Pennsylvania Campus. There were 108 (0.24%) cases of AGUS smears during that time. No clinical information was available for 14 patients, and 19 were lost to follow-up. The charts of the remaining 75 cases were retrospectively reviewed. RESULTS: Tissue specimens were available for 62 of the 75 patients. There were 26 (42%) with no significant histopathologic findings, 13 (21%) with polyps, 5 (8%) cases of endometrial hyperplasia, 2 (3%) with endometrial adenocarcinoma, 12 (19%) with cervical intraepithelial neoplasia (CIN), 1 (2%) with adenosquamous carcinoma of the cervix, 2 (3%) with cervical adenocarcinoma in situ and 1 (2%) case of metastatic breast cancer. The total number of patients with significant histopathology other than polyps was 23 (37%). The median age of the patients was 49 years. There were more cases of endometrial hyperplasia and endometrial cancer (19%) in women 49 years or older than in younger women; only one (3%) case of endometrial hyperplasia was detected in the younger age group (P = .057). Patients who underwent more-aggressive evaluation (colposcopy and biopsies plus endometrial sampling, cone biopsy or hysterectomy) had greater numbers of abnormal histopathologic findings (55%) than patients who underwent endometrial sampling only (21%) or those who underwent colposcopy and biopsy only (33%). This difference approaches statistical significance (P = .057). A significant proportion of patients with a history of CIN and a cytologic diagnosis of AGUS were found to have CIN (47%), while 8% of those with no history of CIN were found to have CIN (P = .002). Fifty percent of patients with a history of cancer (all had breast cancer) and AGUS had abnormal histopathology. Patients with a subclassification of AGUS "favor neoplasia" had a greater proportion of significant histopathology (72%) as compared to AGUS "unspecified" (26%) and AGUS "favor reactive" (20%) (P = .003). CONCLUSION: A significant proportion of women with a cytologic diagnosis of AGUS have abnormal histopathology. Heightened awareness should be raised in patients with AGUS and a history of CIN or cancer and in those with the AGUS subclassification "favor neoplasia."

Evaluating cervical neoplasia. LEEP as an alternative to cold knife conization.

OBJECTIVE: To determine how the loop electrosurgical excision procedure (LEEP) compares to cold knife conization in providing an adequate diagnostic specimen. STUDY DESIGN: Between 1991 and 1995, 95 patients underwent either diagnostic LEEP or cold knife conization at Allegheny University Hospitals. The indications for the procedure were a cytologic/histologic discrepancy, unsatisfactory colposcopic evaluation, positive endocervical curettage or exclusion of invasion. RESULTS: Severe thermal artifact rendered the LEEP specimens uninterpretable in 4.4% of cases. A median number of two passes were required for LEEP excision of the transformation zone. The number of passes correlated with the amount of thermal artifact detected (P = .034). Regarding recurrence patterns, normal follow-up cervical cytology was similar for both groups: 96.7% in the LEEP group vs. 100% in the cold knife conization group. CONCLUSION: We conclude that LEEP is an acceptable diagnostic alternative to traditional cold knife conization. Thermal artifact remains a disadvantage that can be minimized by limiting the number of passes required to obtain a complete specimen.

Intracavitary use of radioactive colloidal phosphorus 32 in the treatment of epithelial ovarian cancer.

The use of radioactive colloidal phosphorus 32 (32P) in the treatment of epithelial ovarian cancer continues to be controversial. One institution's experience with the use of 32P in 30 patients with epithelial ovarian cancer was reviewed retrospectively. One hundred percent of attempts at placement of 32P intra-abdominally were ultimately successful. The complication rate was 11%. Mean clinical (asymptomatic) disease-free survival in patients with stage III ovarian cancer was as follows: 26 months based on absence of disease at reassessment surgery; 26 months based on microscopic residuum; and 30 months based on minimal (< 5 mm) residuum. Mean disease-free survival in patients with early-stage (stages IC through IIC) ovarian cancer was 66 months.

Poorer prognosis in older patients with endometrial adenocarcinoma.

It has been suggested that there are two types of endometrial carcinoma: the first arises in younger women who have hyperestrogenism and has a favorable prognosis and the second occurs in older women, is not associated to estrogen stimulation, and has a poorer prognosis. This study examined the hypothesis that more aggressive carcinomas are found in older patients with no evidence of estrogen stimulation. A retrospective review of all patients (N = 82) with endometrial carcinoma diagnosed and treated at our institution between 1978 and 1990 was undertaken. The following data were analyzed: age at diagnosis, stage, race, histologic type, grade, depth of myometrial invasion, absence or presence of associated hyperplasia, and survival. The mean age of the patients was 64.8 years. Sixty (73%) of the 82 patients were considered estrogen-positive either because of obesity (body mass index > or = 27.3) or the use of unopposed exogenous estrogen. There were no statistically significant differences between estrogen-positive and estrogen-negative patients. Patients > or = 65 years had a 5-year survival of 60% compared with 74% for younger patients. There was a trend toward higher histologic grade among the older patients. Otherwise no statistically significant differences were found between these two groups. Estrogen-negative women > or = 65 years had the worst prognosis with a 5-year survival of 29%. As identified by other investigators, age at diagnosis is a significant indicator of prognosis in patients with endometrial carcinoma. In this series, thin, older (> or = 65 years) women who developed endometrial carcinoma had the worst prognosis.

The effectiveness of the Masterson curette in sampling the endometrial cavity.

The Masterson curette was used to sample the endometrial cavity of 25 women prior to scheduled hysterectomy for benign or malignant pathology. Adequate amount of tissue was obtained in 20 (87%) of 23 patients who did not have endometrial atrophy. The Masterson curettage detected all seven cases of endometrial hyperplasia or adenocarcinoma for a sensitivity of 100%. However, the Masterson curette does not sample the entire endometrial cavity. If abnormal uterine bleeding persists despite normal histology on curettings obtained with the Masterson or other endometrial sampling device, hysteroscopy is recommended.

Thrombocytosis in surgically treated stage IB squamous cell cervical carcinoma (A Gynecologic Oncology Group study).

Thrombocytosis has previously been shown to be an unfavorable prognostic factor in cervical cancer patients treated with irradiation. We evaluated the significance of thrombocytosis (platelet count > 400 x 10(9)/liter in 623 surgically treated patients with stage IB squamous cell carcinoma of the cervix. These patients had no gross evidence of extrauterine disease at the time of exploration, and none had metastasis to the para-aortic nodes. Fifty-nine (9.5%) of these 623 patients had thrombocytosis. The 5-year survival for patients with thrombocytosis was 82% compared to 83.5% for patients with normal platelet count (P = 0.4). Pelvic node metastasis was present in 13 (22%) of 59 patients with thrombocytosis, and 77 (13.7%) of 564 patients with normal platelet count (P = 0.1). There was a significant correlation between tumor size and platelet count. Patients with thrombocytosis had a mean tumor size of 27.9 mm, while it was 20.4 mm in patients without thrombocytosis (P = 0.002). Other factors found to be associated with thrombocytosis in this population were elevated white blood cell (WBC) count (P = 0.009) and history of chronic obstructive pulmonary disease (COPD) (P = 0.02). In a multivariate analysis for thrombocytosis adjusted for COPD, WBC count, and tumor size, tumor size continued to be statistically significant (P = 0.01). These data suggest that thrombocytosis is a marker of tumor burden and not an independent prognostic factor for progression-free interval or survival.

Mullerian adenosarcoma of the uterus with sarcomatous overgrowth.

A case of mullerian adenosarcoma of the uterus with sarcomatous overgrowth is described. The patient was also found to have bilateral polycystic ovaries. This 25 year-old white female presented with irregular vaginal bleeding and was diagnosed as having mullerian adenosarcoma with sarcomatous overgrowth by dilatation, curettage, and biopsy. Total abdominal hysterectomy, bilateral salpingo-oophorectomy with lymph node sampling were performed.

Groin dissection versus groin radiation in carcinoma of the vulva: a Gynecologic Oncology Group study.

PURPOSE: The objective of this study was to determine if groin radiation was superior to and less morbid than groin dissection. METHODS AND MATERIALS: Members of the Gynecologic Oncology Group randomized 58 patients with squamous carcinoma of the vulva and nonsuspicious (N0-1) inguinal nodes to receive either groin dissection or groin radiation, each in conjunction with radical vulvectomy. Radiation therapy consisted of a dose of 50 Gray given in daily 200 centiGray fractions to a depth of 3 cm below the anterior skin surface. RESULTS: The study was closed prematurely when interim monitoring revealed an excessive number of groin relapses on the groin radiation regimen. Metastatic involvement of the groin nodes was projected to occur in 24% of patients based on this Group's previous experience. On the groin dissection regimen, there were 5/25 (20.0%) patients with positive groin nodes. These patients received post-operative radiation. There were five groin relapses among the 27 (18.5%) patients on the groin radiation regimen and none on the groin dissection regimen. The groin dissection regimen had significantly better progression-free interval (p = 0.03) and survival (p = 0.04). CONCLUSION: Radiation of the intact groins as given in this study is significantly inferior to groin dissection in patients with squamous carcinoma of the vulva and N0-1 nodes.

Clinical-pathologic study of stage IIB, III, and IVA carcinoma of the cervix: extended diagnostic evaluation for paraaortic node metastasis--a Gynecologic Oncology Group study.

Three hundred twenty patients were entered into GOG Protocol 63, a clinical-pathologic study of stage IIB, III, and IVA cervical carcinoma. Following the completion of FIGO staging prerequisites, patients had computerized tomography (CT), a lymph-angiogram (LAG), and an ultrasound (US) of the aortic area. If any study was positive, a cytologic or histologic evaluation by fine-needle aspiration or selective paraaortic lymphadenectomy was performed. Paraaortic node dissection was mandated for patients with negative extended staging studies. Results of extended staging evaluations were compared with histologic or cytologic results. Two hundred sixty-four patients were eligible and evaluable. One hundred sixty-seven patients (63%) were stage IIB, 89 (34%) were stage III, and 8 (3%) were stage IVA. Positive paraaortic nodes occurred in 21% of stage IIB, 31% of stage III, and 13% of stage IVA. LAG sensitivity was 79% with a specificity of 73%. Sensitivity of CT and US was 34 and 19%, respectively, with specificities of 96 and 99%, respectively. The frequency of false-negative results with LAG for patients with stage IIB disease was 6%. This decrease is consistent with a stable sensitivity and specificity. These findings suggest that a negative LAG may be adequate to eliminate surgical staging in subgroups with low risk of metastasis to the aortic nodes. Until new noninvasive testing methods are developed, LAG appears to be the most reliable noninvasive examination to evaluate spread of cervical cancer to aortic nodes.

Treatment failure in endometrial carcinoma.

Endometrial carcinoma has been regarded as one of the more curable gynecologic malignancies. Clinical stage, grade, and depth of myometrial invasion are well-established prognostic variables. We examined the clinical course of 520 patients with endometrial carcinoma treated at Walter Reed Army Medical Center and the Naval Hospital, Bethesda, Maryland, between January 1, 1960 and December 31, 1982. Life table 5-year survivals for stages Ia, Ib, II, III, and IV were 89, 92, 77, 27, and 0%, respectively. Compared with patients with grade 1 endometrial adenocarcinomas, significant decreases in survival were noted for patients with grade 2 or 3 endometrial, papillary endometrioid, serous papillary, and clear-cell tumors. There were six treatment-related deaths (1.2%). Thirty-eight patients (7.3%) developed recurrent disease, with a median time to recurrence of 15 months and a median survival of 21 months. Two of 11 patients with pelvic recurrence were salvaged by radiotherapy, whereas none of 27 patients with distant failure survived. Sixteen advanced-stage patients (3.1%) with persistent disease had a median survival of 4.5 months. Patients with advanced disease or unfavorable histologic subtypes responded poorly to conventional therapy. Current salvage treatments are largely ineffective. Combined-modality therapy and systemic adjuvant therapy should be prospectively evaluated in high-risk patient subgroups.

Widespread lymph node metastases in a patient with microinvasive cervical carcinoma.

Lymph node metastasis is uncommon in patients with microinvasive squamous cell carcinoma of the cervix and is particularly unusual in tumors with early stromal invasion. We describe a patient with maximum stromal invasion of 0.8 mm who had extensive pelvic and para-aortic nodal metastases discovered at laparotomy. Despite combined modality therapy, she died with progressive disease. New clinical staging definitions for Stage IA cervical carcinoma incorporate measurement of both depth of invasion and lateral tumor spread and have resolved many of the descriptive controversies surrounding this entity. Our case illustrates that any degree of stromal invasion carries some risk of nodal metastasis. The management of patients with microinvasive carcinoma should be individualized. An abdominal approach should be considered for patients being treated by extrafascial hysterectomy to allow assessment of the regional lymph nodes. Whether more aggressive therapy will influence the outcome for the rare patient with lymph node metastasis is unknown.

Extraperitoneal versus transperitoneal selective paraaortic lymphadenectomy in the pretreatment surgical staging of advanced cervical carcinoma (a Gynecologic Oncology Group study).

Two-hundred and eighty-eight patients with predominately stage IIB or IIIB cervical carcinoma underwent pretreatment surgical staging including selective paraaortic lymphadenectomy (SPAL), followed by pelvic irradiation with or without paraaortic irradiation (RT). Four patients were excluded from analysis (two received no RT and two were insufficiently documented). Of the remaining 284 patients, 128 underwent extraperitoneal (EP) SPAL and 156 transperitoneal (TP) SPAL procedures. Age, race, and stage (clinical and surgical), cell type, paraaortic nodal status, and peritoneal cytology findings were similar in both groups. Complications presumed to arise from operative staging were infection, which was similar for both groups, and vascular injury, which was higher in the TP group, although not statistically significant. Complications subsequent to RT fell into two categories: local-pelvic necrosis, vesicovaginal and rectovaginal fistulas, proctitis, etc., and regional-enterovaginal fistula, bowel obstruction, enteritis, bowel perforation, etc. The frequency of local complications was similar for both EP and TP patients. Utilizing univariant analysis, among regional complications, both bowel obstruction and nonobstructive enteric injuries were observed significantly more often in TP patients than in EP patients (11.5% vs 3.9%, P = 0.03, for both types). Multivariant analysis confirmed these observations. This report supports the conclusions that in advanced cervical carcinoma (1) EP- and TP-SPAL are of similar sensitivity in detecting nodal spread, (2) no significant differences in the frequency of surgical complications could be detected between EP- and TP-SPAL groups, and (3) TP-SPAL is associated with a higher frequency of certain postirradiation regional enteric complications.

Endodermal sinus tumor of the infant vagina treated exclusively by chemotherapy.

A 5-month-old Hispanic female, diagnosed as having endodermal sinus tumor of the vagina, was treated with combination chemotherapy in an attempt to preserve pelvic function. An incisional biopsy was performed before starting chemotherapy. After completion of chemotherapy, no residual disease was found at exploratory laparotomy. The patient received no further therapy and is disease-free 45 months later. This case represents successful treatment of a vaginal endodermal sinus tumor without any operative excision.

Determinants of survival of patients with epithelial ovarian carcinoma following whole abdomen irradiation (WAR).

In an attempt to identify those parameters which represent predictors of clinical outcome, a retrospective review of patients with epithelial ovarian carcinoma who were primarily treated with whole abdominal irradiation (WAR) following staging laparotomy was performed. Complete records with extensive long-term follow-up were available on 102 patients treated from 1962 through 1974. Histopathologic review excluded 18 patients with lesions of low malignant potential. Of the remaining 84 cases there were 12 Stage I (14%), 23 Stage II (27%), 45 Stage III (54%), and 4 Stage IV (5%). Measure of completeness of surgical resection was expressed as the largest diameter of residual gross tumor. Following primary surgical debulking Stages II and III patients, 24 patients had no gross residual disease, 24 patients had less than 2 cm of residual disease, and 20 patients had greater than 2 cm of residual disease. For Stages II and III patients together, 5- and 10-year actuarial survivals were: No gross residual, 69% and 59%; less than 2 cm, 48% and 42%; and greater than 2 cm, 15% and 10%. The technique of administration of WAR did not appear to influence survival. The results of this review support the concept that in selecting WAR for primary treatment of ovarian carcinoma, completeness of cytoreductive surgery should be considered. These data justify a prospective randomized study in patients with minimal residual disease following staging laparotomy comparing WAR with current first-line combination chemotherapy.

Diagnosis of recurrent gynecologic malignancy with fine-needle aspiration cytology.

Between 1980-1985, 177 fine-needle aspirations were performed on 139 patients suspected of having recurrent gynecologic malignancy. Suspected sites of recurrence included a pelvic mass (122), peripheral lymph node (39), and a variety of other locations (16). There were 69 positives, 79 negatives, eight suspicious specimens, and 21 specimens inadequate for interpretation. Excluding suspicious or inadequate specimens, the results of the remaining 148 evaluable aspirations were confirmed by histopathologic correlation (35) or subsequent clinical course (113). Because there were no false positives, the specificity of the technique was 100%. The sensitivity was 68%, with an associated false-negative rate of 32%. The predictive value of a positive was 100%; that of a negative was 57%. An analysis of the false-negative results failed to show a correlation with cell type, lesion location, previous radiotherapy, or previous chemotherapy. The complication rate was less than 1%. These data support the conclusion that fine-needle aspiration cytology is a safe, highly specific method for diagnosing recurrent gynecologic malignancy. However, in patients with negative fine-needle aspiration cytology and suspected recurrent disease, it would appear that further evaluation is indicated.

Evaluation of the scalene lymph nodes in primary and recurrent cervical carcinoma.

Open biopsy of the left scalene lymph nodes has been utilized to identify distant spread of cervical carcinoma in selected groups of patients who do not have other clinical evidence of disseminated disease. Twenty-one patients with primary cervical carcinoma and histologically proven para-aortic lymph node metastases and 10 patients with centrally recurrent tumors underwent scalene lymph node biopsy at Walter Reed Army Medical Center or the Naval Hospital, Bethesda, Maryland, between July 1, 1979 and June 30, 1985. All patients undergoing scalene node biopsy had clinically negative physical examinations. There were no surgical complications. All 31 biopsies were negative for metastatic tumor. Combined with previously reported data from this institution, 3 of 28 patients (11%) with primary cervical carcinoma and involved para-aortic nodes, and 6 of 35 patients (17%) with centrally recurrent disease had subclinical scalene node metastases. Patients with clinically suspicious scalene lymphadenopathy had fine needle aspiration cytology performed to document metastatic disease. The success of this technique has eliminated the need for open biopsy in these patients. Scalene node biopsy provides valuable prognostic information in patients with cervical cancer who have positive para-aortic lymph nodes. It also obviates surgical exploration in some patients felt to have resectable recurrent disease who actually have subclinical distant spread.

Surgical pathologic spread patterns of endometrial cancer. A Gynecologic Oncology Group Study.

The surgical pathologic features of 621 patients with Stage I carcinoma of the endometrium are presented. All patients were treated with primary surgery consisting of total abdominal hysterectomy, bilateral salpingo-oophorectomy, selective pelvic and paraaortic lymphadenectomy and peritoneal cytology. An appreciable number of patients (144-22%) with Stage I cancers have disease outside of the uterus (lymph node metastasis, adnexal disease, intraperitoneal spread and/or malignant cells in peritoneal washings). Multiple prognostic factors particularly grade and depth of invasion are related to extrauterine disease. This study adds credence to the primary surgical approach with individualized postoperative therapy as indicated.

Radical hysterectomy and pelvic lymphadenectomy for stage IB carcinoma of the cervix: 21 years experience.

From September 1971 through December 1982, 153 patients with Stage IB carcinoma of the cervix underwent radical hysterectomy and pelvic lymphadenectomy at two of the teaching hospitals of the Uniformed Services University of the Health Sciences. Records were retrospectively analyzed and independent pathologic review was performed. All surgical procedures were performed by fellows or senior residents under the direct supervision of the gynecologic oncology staff of the Walter Reed Army Medical Center or the Naval Hospital, Bethesda, Maryland. In this series, IB carcinoma was defined as squamous carcinoma clinically confined to the cervix with invasion greater than 5 mm from the basement membrane or any adenocarcinoma confined to the cervix. The average age of the patients was 38.3 years. The histologic types were squamous in 72%, adenocarcinoma in 16%, and adenosquamous in 10.5%. The mean operating time was 5 hr and 40 min with an average blood loss of 1800 cc. There were two ureterovaginal and two vesicovaginal fistulae for an overall fistula rate of 2.6%. Actuarial survival for these 153 patients is 84%. This extends the previous series of R. C. Park, W. E. Patow, R. E. Rogers, and E. A. Zimmerman, Obstet. Gynecol. 41, 117-122 (1973) of 122 cases collected from 1961 to September 1971 to 275 cases. In comparing the two time periods, no significant differences were found in operative technique or complications, but there was a change in the incidence of adenocarcinoma and mixed cell types and a difference in survival. A relatively higher incidence of more aggressive tumors may indicate the need for different therapeutic approaches in the future.