Flow cytometric DNA analysis of early stage adenocarcinoma of the cervix.

OBJECTIVE: The aim of this study was to determine the utility of DNA flow cytometry as a prognostic indicator for risk of recurrence and overall survival in patients with early stage adenocarcinomas of the uterine cervix. METHODS: DNA flow cytometry was performed to determine ploidy, DNA index, and proliferative index in 66 women with stage IB and IIA pure mucinous adenocarcinomas of the cervix treated by primary surgical therapy with radical hysterectomy and pelvic lymphadenectomy. Fifty-seven of 66 (86.3%) tissue samples were analyzable. Three sections were obtained from paraffin-embedded tissue blocks containing primary tumor. Flow cytometric results, along with other known prognostic variables for risk for recurrent disease and survival, were analyzed using the Cox regression proportional hazards model and survival curves generated by the Kaplan-Meier method. RESULTS: Of 57 interpretable samples, DNA ploidy patterns were 18 (27%) diploid, 8 (12%) tetraploid, and 31 (47%) aneuploid. Thirteen of 66 patients (20%) experienced recurrence with a median time to recurrence of 1.6 years. No significant correlation was noted between DNA ploidy and risk of recurrence (P = 0.429). Multivariate analysis confirmed that positive metastatic lymph nodes were associated with risk of recurrence (P < 0.001). In node-negative patients, a high proliferative index (S% + G(2)M% > 20%), measured as a continuous variable, was the only significant factor for tumor recurrence (P = 0.002). CONCLUSION: DNA ploidy does not predict a patient's risk for tumor recurrence; however, a high proliferative index value warrants further investigation as a potential prognostic indicator for risk of recurrent disease in patients with adenocarcinoma of the uterine cervix.

Flow-cytometric DNA analysis of early stage adenocarcinoma of the cervix.

OBJECTIVE: The purpose of this study was to determine the utility of DNA flow cytometry as a prognostic indicator for risk of recurrence and overall survival in patients with early stage adenocarcinomas of the uterine cervix. METHODS: DNA flow cytometry was performed to determine ploidy, DNA index, and proliferative index in 66 women with stages IB and IIA pure mucinous adenocarcinomas of the cervix treated by primary surgical therapy with radical hysterectomy and pelvic lymphadenectomy. Fifty-seven of 66 (86.3%) tissue samples were analyzable. Three sections were obtained from paraffin-embedded tissue blocks containing primary tumor. Flow-cytometric results, along with other known prognostic variables for risk for recurrent disease and survival, were analyzed using Cox regression proportional hazards model, and survival curves were generated by the Kaplan-Meier method. RESULTS: Of 57 interpretable samples, DNA ploidy patterns were 18 (27%) diploid, 8 (12%) tetraploid, and 31 (47%) aneuploid. Thirteen of 66 patients (20%) experienced recurrence with a median time to recurrence of 1.6 years. No significant correlation was noted between DNA ploidy and risk of recurrence (P = 0.429). Multivariate analysis confirmed that positive metastatic lymph nodes were associated with risk of recurrence (P < 0.001). In node-negative patients, a high proliferative index (S% + G(2)M% > 20%), measured as a continuous variable, was the only significant factor for tumor recurrence (P = 0.002). CONCLUSION: DNA ploidy does not predict a patient's risk for tumor recurrence; however, a high proliferative index value warrants further investigation as a potential prognostic indicator for risk of recurrent disease in patients with adenocarcinoma of the uterine cervix.

Osteitis pubis after Marshall-Marchetti-Krantz urethropexy: a pubic osteomyelitis.

OBJECTIVE: Our purpose was to review cases of osteitis pubis encountered at our institution after Marshall-Marchetti-Krantz retropubic urethropexy. STUDY DESIGN: The charts of patients diagnosed with osteitis pubis subsequent to Marshall-Marchetti-Krantz retropubic urethropexy from 1980 to 1994 were reviewed. RESULTS: Fifteen cases of osteitis pubis were diagnosed after 2030 Marshall-Marchetti-Krantz procedures (0.74%). Onset of symptoms related to osteitis pubis began a mean of 69.8 days postoperatively (range 10 to 459 days). Although initial plain films of the symphysis pubis were normal in 7 (54%), radiographic abnormality was eventually demonstrated in all a mean of 25.7 weeks after surgery (range 4 to 78 weeks). A variety of conservative treatments resulted in symptomatic relief in 47%. Seven of the remaining patients underwent operative therapy with partial or complete relief noted in all. Subsequent bone cultures were positive in 5 (71%). At follow-up a mean of 58 months after the Marshall-Marchetti-Krantz procedure complete resolution of symptoms was noted in 33% and continued pain or ambulatory difficulty in the remainder. There was no relationship between postoperative urinary tract infections, postoperative complications, presenting sign of fever, elevated leukocyte count or sedimentation rate, and subsequent operative intervention (P > .05). CONCLUSIONS: Osteitis pubis after urogynecologic surgery is an uncommon event requiring aggressive surgical and antibiotic therapy. When bone cultures are performed, a microbial cause may be demonstrated in as many as 71% of patients.

Surgical correction of an acquired vaginal stricture in a llama, using a carbon-dioxide laser.

An acquired vaginal stricture in a llama secondary to trauma from uterine torsion during gestation was repaired, using a carbon-dioxide laser. The procedure was accomplished by use of epidural anesthesia with the llama in a standing position. Repeated dilation of the vagina was required after surgery; however, the llama subsequently mated and conceived, and a male cria was delivered by cesarean section at the end of a full-term gestation.

Pelvic exenterations: supralevator, infralevator, and with vulvectomy.

The purpose of this study was to determine whether the different types (I, II, and III) of pelvic exenterations have prognostic implications in regard to operative features, postoperative complications, and survival. The records of the 133 patients who underwent pelvic exenteration at the Mayo Clinic from 1977 to 1986 were reviewed. The records were abstracted for duration of hospitalization, febrile morbidity, duration of operation, operative blood loss, number of blood transfusions, performance of a perineal phase, development of an omental carpet, vaginal reconstruction, reoperation, additional tissue resection, complications, and survival. Statistically significant differences were noted univariately between types I, II, and III in regard to the development of an omental carpet, whether or not vaginal reconstruction was done, the performance of a perineal phase, the resection of additional tissues, and the duration of hospitalization. The operative and postoperative morbidity and survival were not influenced significantly by the type of exenteration. The subclassification of the exenteration groups into type I (supralevator), type II (infralevator), and type III (with vulvectomy) is helpful to facilitate understanding of the extent of resection of the pelvic structures and the anatomical changes associated with each operation. Subgrouping facilitates communication, not only between pelvic surgeons but also with third-party payers.

Transverse vaginal septum associated with tubal atresia.

Transverse vaginal septum is a defect of vertical fusion during embryogenesis of the vagina. The estimated incidence is 1 per 30,000 to 84,000 women. It is infrequently associated with genitourinary tract, gastrointestinal tract, musculoskeletal, and cardiac malformations. Previous reports of transverse vaginal septum have included unilateral absence of the fallopian tube and ovary and absence of the proximal portion of the fallopian tube. This report describes bilateral tubal atresia associated with a transverse vaginal septum. A 17-year-old nulligravida sought medical assessment because of primary amenorrhea and cyclic pelvic pain. Physical examination revealed a blind vaginal pouch and a tender pelvic mass. Radiologic studies showed a transverse vaginal septum 1.5 cm distal to the cervix. The septum was resected with laparoscopic guidance, and bilateral fallopian tubal atresia was noted. The pelvis was otherwise normal. Patients commonly have a pelvic or abdominal mass, pain, and amenorrhea at time of expected menarche. Surgical resection is the treatment of choice. Postoperative dilation may be necessary to prevent restenosis. Outlook for pregnancy is encouraging despite a higher than normal incidence of spontaneous abortion and endometriosis in such patients.

Cyclophosphamide, cisplatin, and leuprolide acetate in patients with debulked stage III or IV ovarian carcinoma.

A phase II study of cyclophosphamide, cisplatin, and leuprolide acetate after debulking of stage III or IV ovarian carcinoma was conducted in 33 patients through a cooperative group study involving 11 institutions. The intent was to determine whether the addition of a gonadotropin-releasing hormone analogue would alter the response rates and toxicity profile of cyclophosphamide and cisplatin in patients with advanced ovarian cancer. Twenty-nine patients completed all 6 planned cycles. Of the 19 patients who had second-look laparotomy, 12 had persistent disease and 7 were negative for disease. The use of a gonadotropin-releasing hormone with combined chemotherapy did not alter the toxicity profile or the effectiveness of chemotherapy when comparisons were made with historical controls.

Humoral hypercalcemia associated with a dysgerminoma.

A 16-year-old girl sought medical attention at the Mayo Clinic because of a 4.5-kg weight loss, hypercalcemia, and a pelvic mass. Preoperatively, the level of the beta-subunit of human chorionic gonadotropin was 147 IU/liter. After a brief period for observation and hydration, abdominal exploration revealed a stage III dysgerminoma; total abdominal hysterectomy and bilateral salpingo-oophorectomy were performed. Within the dysgerminoma, syncytial giant cells expressed human chorionic gonadotropin-positive immunostaining in the cytoplasm. Postoperatively, the value of the beta-subunit of human chorionic gonadotropin decreased rapidly. The patient received whole-abdomen irradiation 4 weeks postoperatively, after which the level of calcium returned to normal. The patient has been free of disease for more than 7 years.

Giant ovarian leiomyoma associated with ascites and polymyositis.

BACKGROUND: Primary ovarian leiomyoma is rare. Most cases are asymptomatic; this benign neoplasm is usually found incidentally on routine pelvic examination, at surgery, or at autopsy. CASE: We present what we believe to be the first case of ovarian leiomyoma associated with ascites and polymyositis, both of which resolved after oophorectomy. This case emphasizes the important fact that preoperative evaluation may be inaccurate. CONCLUSION: Excision of a pelvic mass with histologic evaluation remains the only reliable way to establish a diagnosis.

Invasive vaginal carcinoma: analysis of early-stage disease.

From 1960 through 1987, 89 patients with stage I (44 patients) or II (45 patients) vaginal carcinoma (excluding melanomas) were treated primarily at the Mayo Clinic. Treatment consisted of surgery alone in 52 patients, surgery plus radiation in 14, and radiation alone in 23. The median duration of follow-up was 4.4 years. The 5-year survival (Kaplan-Meier method) was 82% for patients with stage I disease and 53% for those with stage II disease (p = 0.009). Analysis of survival according to treatment did not show statistically significant differences. This report is consistent with previous studies showing that stage is an important prognostic factor and that treatment can be individualized, including surgical treatment for primary early-stage vaginal cancer.

Suture entrapment and secondary ureteral obstruction.

During the 6-year period ending in 1988, suture entrapment and secondary postoperative ureteral obstruction occurred in 18 (0.33%) of the 5379 patients who underwent major pelvic operations for benign conditions. Sixteen cases occurred after vaginal surgery and two after abdominal hysterectomy. Placement of the McCall suture or sutures for elevation of a bladder neck caused ureteral entrapment most frequently. Early diagnosis was facilitated by comparison of preoperative and postoperative serum creatinine levels. The mean change in serum creatinine level in patients with unilateral obstruction was an increase of 0.8 mg/dl. Treatment by either antegrade placement of ureteral stents or abdominal exploration with deligation or ureteroneocystotomy was successful in all cases. Retrograde placement of ureteral stents was unsuccessful.

Gynecologic cancer in patients with subacute cerebellar degeneration predicted by anti-Purkinje cell antibodies and limited in metastatic volume.

Between 1982 and 1989, 19 patients with gynecologic carcinoma, paraneoplastic cerebellar degeneration, and seropositivity for anti-Purkinje cell cytoplasmic antibodies were identified at our institution. Seven of the patients had no clinical, computed tomographic, or magnetic resonance imaging evidence of cancer but had undergone laparotomy solely because anti-Purkinje cell antibodies were found in their serum; all had high-grade adenocarcinoma. Cerebellar symptoms preceded or coincided with the initial cancer diagnosis in 15 patients and preceded the diagnosis of recurrent cancer in 4 patients. The cancers were 14 ovarian, 2 fallopian tube, 2 surface papillary, and 1 poorly differentiated metastatic adenocarcinoma in a periaortic lymph node. Two remarkable surgical observations in patients with high-grade ovarian and tubal cancers were the conspicuous lack of peritoneal implants and the small metastatic volume. A comparison of the 8 patients who had primary stage III cancer with 24 matched control patients without paraneoplastic cerebellar degeneration revealed no difference in primary tumor volume but a significantly smaller volume of metastatic tumor in the seropositive group (P = 0.05). Anti-Purkinje cell antibodies were not detected in 111 neurologically normal patients with advanced ovarian cancer. The small metastatic volume in the face of high-grade and advanced stage malignancy in seropositive patients with paraneoplastic cerebellar degeneration suggests that an immune response to the tumor (presumably cross-reactive with cerebellar cells) may impair the metastatic process. Earlier diagnosis and treatment of cancer, based on prompt serologic testing, may offer an improved neurologic and oncologic prognosis.

Cyclophosphamide-cisplatin versus cyclophosphamide-carboplatin in stage III-IV ovarian carcinoma: a comparison of equally myelosuppressive regimens.

Between March 1985 and January 1987, 103 women with histologically proven stage III-IV ovarian carcinoma were randomly allocated to groups receiving monthly intravenous regimens of 1 g of cyclophosphamide/m2 plus either 60 mg of cisplatin (CDDP)/m2 or 150 mg of carboplatin (CBDCA)/m2 for 1 year unless disease progressed earlier. The groups were well balanced according to the stratification factors (age, histologic differentiation, extent of residual disease, and performance score), and both treatments were well tolerated and produced similar median first-course leukopenia (2,200 and 2,000 cells/microL) and thrombocytopenia (220,000 and 202,500 cells/microL). The CBDCA regimen was less emetogenic. After an interim analysis in January 1987 revealed superior progression-free survival for the group of 53 patients receiving CDDP (P = .005), the study was closed to further accrual. Those 24 patients still receiving CBDCA were encouraged to cross over to the CDDP-based regimen and 21 of them did. Following treatment crossover, the relative risk of death associated with original allocation to CBDCA receded from 1.79 to 0.97, indicating success of the salvage treatment using the CDDP-based regimen. This aborted study demonstrated the superiority of CDDP over CBDCA when the two platinum compounds were compared at equally myelosuppressive low doses in combination with 1 g of cyclophosphamide/m2. If CDDP is to be supplanted by CBDCA, larger, more myelosuppressive doses of CBDCA will be required. The platinum drug antitumor effect is a critically important therapeutic feature of this combination.

Evaluation of treatment and survival after positive second-look laparotomy.

During the 9-year interval 1977 through 1985, of 250 patients undergoing second-look laparotomy, 116 (46%) were found to have clinically occult ovarian carcinoma. Salvage therapy consisted of external irradiation in 37, intraperitoneal 32P in 12, chemotherapy in 63, and no therapy in 3 or other therapy in 1. Eligible follow-up time ranged from 1 to 9 years. The Kaplan-Meier projected median time-to-progression and survival were 15 and 22.5 months, respectively, with 4-year progression-free and overall survival rates being 21 and 27%, respectively. Survival was independent of the original stage of disease but was significantly influenced by histologic grade and microscopic (55%) versus macroscopic (19%) residual tumor after the laparotomy. Projected 4-year salvage rates in patients with microscopic or residual disease less than or equal to 5 mm was 72, 39, and 19% for intraperitoneal 32P, external irradiation (33/37, whole abdominopelvic), and chemotherapy, respectively. However, multivariable analysis demonstrated that histologic grade and isotope therapy retained independent influence on survival, but no therapeutic advantage for external irradiation over chemotherapy was demonstrable. Furthermore, use of regimens that were identical to, partially altered from, or different from the first-trial agents did not affect chemotherapy salvage rates.

Preoperative evaluation of serum CA 125 levels in premenopausal and postmenopausal patients with pelvic masses: discrimination of benign from malignant disease.

CA 125 levels were measured in 158 patients with palpable pelvic masses who were about to undergo diagnostic laparotomy. When the 68 patients found to have cancer were compared with the 90 patients with benign disease, those with malignancies were significantly older, were more frequently postmenopausal, and had significantly higher values of serum CA 125. Patients with benign pelvic masses had CA 125 levels greater than 65 U/ml in 8% of cases, whereas those with malignancies had CA 125 levels greater than 65 U/ml in 75% of cases. If only those patients who had frankly malignant, primary, nonmucinous epithelial ovarian carcinomas were considered, CA 125 levels greater than 65 U/ml predicted malignancy with a sensitivity of 91% for all patients. Greater sensitivity and specificity were observed in the postmenopausal subgroup than in the premenopausal subgroup. In the postmenopausal group with a 63% prevalence of ovarian cancer the predictive positive value was 98% and the predictive value negative was 72%. In a premenopausal population with a 15% prevalence of ovarian cancer the predictive value for a positive test was 49%, while the predictive value for a negative test was 93%.

Recurrent disease after negative second-look laparotomy in stages III and IV ovarian carcinoma.

Between 1977 and 1984, second-look laparotomy to evaluate disease status after adjuvant chemotherapy was performed in 134 patients originally presenting with advanced epithelial ovarian carcinoma. Surgical and histologic assessment did not detect persistent disease in 50 patients (37%). Recurrent carcinoma was subsequently documented in 15 patients (30%), all failures occurring within the abdominal cavity or the retroperitoneal space. Several patient subgroups at high risk for recurrence after negative second-look laparotomy are identified that might benefit from additional adjunctive therapy. Because of different treatment-associated morbidities, the corresponding sensitivities and specificities of the high-risk groups may assist subsequent treatment selection.