Outcomes following surgery and adjuvant radiation in stage II endometrial adenocarcinoma.

PURPOSE: To evaluate locoregional control, disease free survival, and overall survival in patients treated with surgery and adjuvant radiation for stage II adenocarcinoma of the endometrium. Secondary goals include identification of prognostic factors and the comparison of toxicity profiles after vaginal cuff brachytherapy (VB) alone or combined with pelvic external beam radiation therapy (EXT). MATERIALS AND METHODS: All patients receiving adjuvant radiation at the University of Wisconsin following surgery for FIGO stage II adenocarcinoma of the endometrium between January 1991 and December 2006 were retrospectively reviewed. RESULTS: Between January 1991 and December 2006, 71 patients with FIGO stage II adenocarcinoma of the endometrium (23 stage IIA, 48 stage IIB) received adjuvant radiation at the University of Wisconsin. Fifty patients were treated with EXT and VB, twenty with VB alone, and one with EXT alone. At a mean follow-up of 5.1 years (range, 0.5-16.8 years), 5-year overall and disease-free survival were both 82%. Factors associated with an increased risk for recurrence include depth of myometrial invasion (p=0.005) and lymphovascular invasion (p=0.02). Receiving EXT was significantly associated with increased depth of myometrial invasion (p=0.007), higher grade (p=0.003), and less extensive surgery (p=0.01). Of the nine recurrences, three were initially local and six were distant recurrences alone. Grade 2 or greater acute and late side effects were significantly greater with EXT therapy compared to VB alone (p<0.0001 and p=0.02, respectively), although severe toxicities (grade 3 or greater) were limited with either modality. DISCUSSION: Local recurrence rates remain low after surgery and adjuvant radiation therapy for stage II endometrial cancer using a combination of VB and EXT tailored to the surgical and pathologic features. VB alone resulted in fewer toxicities without an increased recurrence risk compared to the combination of EXT and VB, suggesting that VB without EXT is sufficient for patients with low-risk histopathologic features and comprehensive surgical staging with complete lymphadenectomy.

Screening for occult nodal metastasis in squamous cell carcinoma of the vulva.

Metastases to inguinofemoral lymph nodes in patients with carcinoma of the vulva alter the prognosis and treatment of this disease. Our goal was to determine if immunohistochemical staining could reveal occult metastatic nodal disease not detected with routine hematoxylin and eosin staining. We retrospectively examined a total of 110 lymph nodes from 10 patients who had undergone lymph node dissection and found to have all negative nodes. Paraffin embedded lymph nodes were immunostained with a monoclonal antibody directed against multiple low- and high-molecular weight cytokeratins. Micrometastases were not detected in any lymph nodes examined with immunohistochemistry. All positive and negative controls yielded satisfactory results. It is concluded that immunohistochemistry with cytokeratin antibodies does not provide greater sensitivity than routine hematoxylin and eosin staining for the detection of nodal metastases in vulvar carcinoma.

Paclitaxel, carboplatin, and hexamethyl-melamine (taxchex) as first-line therapy for ovarian cancer.

BACKGROUND: The addition of hexamethylmelamine to therapy with cisplatin, cyclophosphamide, and doxorubicin significantly enhanced outcomes of patients with advanced ovarian cancer. Hexamethylmelamine, also known as altretamine, has potent antineoplastic activity when used as a single agent in patients who have failed to respond to both platinum-based and paclitaxel therapy. We have conducted a pilot study to evaluate the efficacy and safety of adding this drug to the popular ovarian cancer regimen of paclitaxel plus carboplatin. METHODS: Patients with advanced ovarian, fallopian tube, or primary peritoneal cancer (International Federation of Gynecology and Obstetrics stages IIA, IIIC, and IV) were prospectively enrolled to receive six cycles, repeated every 4 weeks, of paclitaxel (150 mg/m2 i.v., day 1), carboplatin (AUC 5.0 i.v., day 1), and hexamethylmelamine (150 mg/m2 p.o., days 2-15). Colony stimulating factors were prohibited. Response and toxicity were monitored by use of Eastern Cooperative Oncology Group criteria. RESULTS: Twenty patients were enrolled, 18 with ovarian cancer, one with fallopian tube cancer, and one with peritoneal cancer; 17 of these patients were evaluable for response and toxicity. At a median follow-up of 6.5 months, 13 of the patients had a complete response (76%), and four had progressive disease. Three of those with a complete response had a recurrence within 1 year of completing treatment. Toxicity was acceptable, with myelosuppression the most severe adverse effect; one patient had grade 3 anemia, one patient had grade 4 thrombocytopenia, and 12 patients had grade 4 neutropenia. Quality of life showed improvement over the course of therapy, particularly in the physical well-being subscale. CONCLUSION: The addition of hexamethylmelamine to paclitaxel and carboplatin is a well-tolerated multidrug combination for women with advanced ovarian cancer that deserves further testing in a phase III study.

Familial ovarian germ cell cancer: report and review.

Ovarian germ cell cancers are rare malignancies accounting for less than 5% of all ovarian cancers. We present a family in which three closely related women were diagnosed with ovarian germ cell malignancies. This family's cancer history prompted a family history investigation of women treated for ovarian germ cell malignancies in the Gynecologic-Oncology Clinic at the University of Wisconsin. One of the eight patients whose family histories were reviewed had an uncle who had been diagnosed with testicular germ cell cancer. A review found six other previously reported families in which more than one relative had been diagnosed with a malignant ovarian germ cell tumor. Additionally, several cases of families with both males and females diagnosed with germ cell cancers have been documented. The low incidence of ovarian germ cell cancers suggests that multiple occurrences in the same family may not be due to chance. Rather, it is possible that a gene conferring susceptibility to ovarian germ cell cancers, and possibly to germ cell tumors in males as well, is present in at least some of these families.

Transforming growth factor-alpha levels in the serum and ascites of patients with advanced epithelial ovarian cancer.

A variety of cytokines have been identified to play a role in ovarian cancer. In this pilot study, we sought to determine whether transforming growth factor-alpha (TGF-alpha) was detectable in the serum and ascites of women with advanced stage epithelial ovarian cancer. TGF-alpha was measured using an enzyme-linked immunosorbent assay and was present in 18 of 25 control sera. Prior to treatment for stage III or IV epithelial ovarian cancer, 18 patients had undetectable serum levels of TGF-alpha, while 18 had values ranging from 10.6 to 531.7 pg/ml. The group with undetectable levels had a 6-month greater median survival; detectable TGF-alpha might be a negative prognostic indicator. In a separate group undergoing second-look laparotomy, differences in median TGF-alpha values versus controls and the primary study group approached significance. TGF-alpha was detected in significantly more control peritoneal fluid samples than in patient ascites. A larger study is warranted.

Trends in United States ovarian cancer mortality, 1979-1995.

OBJECTIVE: To describe the epidemiology of ovarian cancer mortality in the United States from 1979 to 1995. METHODS: The mortality data of the Centers for Disease Control and Prevention were accessed using the Wide-ranging Online Data for Epidemiologic Research (WONDER). We selected all deaths among women with International Classification of Diseases, Ninth Revision (ICD-9) code 183.0 (ovarian malignant neoplasm). Mortality data for the years 1979-1995 were age-adjusted to the United States 1990 female population, and mortality rates for each year were calculated for females of all ages by age category, by race, and by geographic location. Trends were obtained for the periods 1979-1983 to 1991-1995, and the impact on the number of ovarian cancer deaths was calculated. RESULTS: Age-adjusted ovarian cancer mortality rates have changed little in the United States from 1979 to 1995, but rates are increasing in older women (65 years and older) and decreasing in younger women. Age-adjusted mortality rates are higher among whites than in blacks. Ovarian cancer mortality rates are higher in northern compared with southern states. CONCLUSION: The trends in ovarian cancer mortality among younger and older women parallel published changes in incidence and may be due to changes in risk factors, such as the use of oral contraceptives. The reasons for the higher ovarian cancer death rates in northern states are unknown. Better understanding of how modifiable risk factors and treatment methods affect ovarian cancer mortality trends is needed.

Outpatient vaginal cuff brachytherapy for endometrial cancer.

Petereit DG, Tannehill SP, Grosen EA, Hartenbach EM, Schink JC. Outpatient vaginal cuff brachytherapy for endometrial cancer. The objective of this study was to determine the efficacy and complications of postoperative high-dose-rate (HDR) vaginal-cuff brachytherapy (VCB) in patients with endometrial carcinoma. Between August 1989 to September 1997, 191 patients were treated postoperatively after a total abdominal hysterectomy and bilateral salpingo-oophorectomy (TAH/BSO) with outpatient adjuvant HDR VCB for low-risk endometrial cancer (IB-84%, grade 1 or 2-96%). Patients were treated with 2 HDR fractions, delivered one week apart while under conscious sedation (16.2 Gy X 2 to the vaginal surface). All clinical endpoints were calculated using the Kaplan Meier method. The median time in the brachytherapy suite was 60 min in which no acute complications were observed. The 30-day morbidity and mortality rates were both 0%. With a median follow-up of 38 months (12-82 months), the 4-year survival, relapse-free survival, and vaginal-control rates were 95%, 98%, and 100%, respectively. One patient developed a colo-vaginal fistula at 5 years. Adjuvant HDR VCB in 2 outpatient insertions produced 100% vaginal control rates with minimal morbidity. The advantages of high dose-rate compared to low dose-rate vaginal brachytherapy include patient convenience, markedly shorter treatment times (1 h per insertion), and reduction in the cost and potential morbidity of hospitalization. HDR brachytherapy approach is a cost-effective alternative to either low-dose-rate brachytherapy or whole pelvic radiotherapy in carefully selected patients.

Vascular endothelial growth factor (VEGF) expression and survival in human epithelial ovarian carcinomas.

Vascular endothelial growth factor (VEGF) expression and microvessel density were studied in cases of advanced epithelial ovarian carcinoma to evaluate their usefulness as prognostic variables. Tumor samples from 18 patients with advanced stage serous epithelial ovarian cancer were evaluated for VEGF expression by reverse-transcriptase polymerase chain reaction (RT-PCR) analysis. Immunohistochemical study of corresponding archival tissues with an antibody to von Willebrand factor (vWF; FVIII-RA) was used for tumor microvessel count determinations. The correlation of VEGF expression and mean microvessel counts was determined by an unpaired t-test. Survival analysis for known prognostic factors and VEGF expression was performed. Survival distributions were calculated by the product limit of Kaplan and Meier and significant differences between distributions were analyzed with a log rank test. From the RT-PCR analysis of tumor VEGF expression, 12 samples were found to be strongly positive, whereas six samples had low/negative VEGF expression. The median survival was 60 months for the VEGF-low/negative group and 28 months for the VEGF-positive group (P = 0.058). Other prognostic variables had minimal impact on survival, i.e. age < 65 years (P = 0.873), FIGO stage (P = 0.06), grade (P = 0.236) and debulking status (P = 0.842). Fourteen of 18 tumor specimens were suitable for microvessel counting. The mean microvessel counts of the VEGF-positive group and the VEGF-negative group were 27/hpf and 35/hpf, respectively (P = 0.16). In this preliminary analysis, high VEGF expression in epithelial ovarian carcinomas was associated with poor overall survival. Further study will be necessary to elucidate the lack of association of VEGF expression and tumor microvessel counts.

The genetics of ovarian cancer: concepts in testing and counseling.

The discovery and sequencing of the BRCA1 gene is an exciting breakthrough for women and health care providers. BRCA1 is associated with inherited breast and ovarian cancer and the body of scientific information regarding its role in ovarian cancer is growing rapidly. The impact of this knowledge on counseling women with a family history of breast or ovarian cancer is profound. This review provides information about familial ovarian cancer syndromes and the emerging role of genetic testing in women with an inherited susceptibility for cancer.

The role of operative laparoscopy in gynecologic oncology.

The potential applications of operative laparoscopy have expanded with improvements in technology and instrumentation. With newly developed techniques to complete both pelvic and paraaortic lymph node dissection, the use of the laparoscope has increased in patients with pelvic malignancies. Gynecologic oncologists are currently incorporating the techniques of operative laparoscopy in the management of patients with cervical, endometrial, and ovarian cancer. Multicenter prospective clinical trials are necessary to further define the role of laparoscopy in gynecologic oncology.

Nonsurgical management strategies for the functional complications of ileocolonic continent urinary reservoirs.

Urinary diversion with creation of a continent ileocolonic reservoir was performed in 25 patients with gynecological malignancies at our institution between September 1989 and September 1994. A retrospective review was conducted and cases were analyzed for functional complications associated with reservoir formation. Functional reservoir complications were defined as (1) difficulty with catheterization, (2) reservoir fistulae, (3) reservoir stones, and (4) ureteral stenosis. Management strategies and outcomes for these complications were determined. All patients had received prior pelvic radiation therapy. There was no surgical mortality. Median follow-up was 21 months, and 16 patients (64%) are currently alive. Fourteen of the patients (56%) had one or more complications attributable to a functional aspect of the continent reservoir. Two patients had difficulty with catheterization (8%), two patients had reservoir leak (8%), and one patient had reservoir stones (4%). Nonsurgical management strategies were used in these cases including balloon dilation of the ileocecal valve, stomal dilation, ureteral stenting, percutaneous nephrostomy, and endoscopic lithotripsy. All cases of catheterization problems, reservoir fistulae, and reservoir stones were resolved with nonoperative techniques. Thirteen of 50 ureters (26%) had some degree of stenosis. Percutaneous balloon dilation was utilized in nine cases of ureteral stenosis. Relief of stenosis was complete in five, partial in two, and not achieved in two of the cases. No patients required a reoperation for a reservoir complication. In conclusion, continent ileocolonic urinary diversion can be performed in patients previously treated with radiotherapy; however, functional reservoir problems may occur. Interventional radiology strategies are useful in managing many of these problems and reexploration can be successfully avoided.

Recurrent squamous cell carcinoma in a rectus abdominis neovagina.

The development of a carcinoma in a neovagina is rare. Most neovaginal neoplasias have been carcinomas in situ in the skin graft. To date, there has not been a report of a neovaginal carcinoma in a myocutaneous flap. This report is the first of a squamous cell carcinoma arising in a neovagina constructed from a rectus abdominis myocutaneous flap.

The utility of preoperative screening colonoscopy in gynecologic oncology.

The American Cancer Society (ACS) recommends that asymptomatic women, age 50 and over, undergo sigmoidoscopy every 3 to 5 years, after two negative yearly exams. Epidemiologic evidence suggests that women with gynecologic or breast cancers have an increased risk of developing colon cancer. It is unclear whether the ACS guidelines are applicable for women with a new diagnosis of gynecologic malignancy. This retrospective study was undertaken to assess the usefulness of preoperative colonoscopy in our gynecologic oncology patient population. Patients undergoing evaluation for a major operative procedure for known or suspected gynecologic malignancies were referred for colonoscopy at the discretion of their attending surgeon. Five hundred patients' charts were reviewed to identify 212 patients in whom preoperative colonoscopy was performed (the study group). In this group, 17 cases of colonic polyps, 5 cases of synchronous colon cancer, and 2 cases of cancer metastatic to the colon were discovered, representing 11% of the study group. Whereas 23% of the patients screened were less than 50 years of age, only two cases of polyps occurred in this age group, and no cases of cancer. Patients aged 70 or greater made up 28% of the study group, but accounted for 41% of the cases of polyps and 40% of the colon cancers. Twenty-nine percent of the study group had adenocarcinoma of the endometrium, representing 7 of 17 cases of polyps, 1 of 5 colon cancers, and 1 of 2 metastatic cancers. Although this retrospective study involved colonoscopy, the locations of the observed lesions were within the theoretic reach of a flexible sigmoidoscope in 75% of cases. We conclude that in the preoperative workup of gynecologic oncology patients, no colon screening is needed in the asymptomatic patient less than 50 years of age. ACS guidelines are appropriate for patients aged 50-70, but for those 70 or greater we would consider full colonoscopy.

A novel strategy using G-CSF to support EMA/CO for high-risk gestational trophoblastic disease.

EMA/CO (etoposide-methotrexate-actinomycin D and Cytoxan-Oncovin) is an effective and well-tolerated chemotherapy regimen for the treatment of high-risk gestational trophoblastic disease. However, it is associated with significant neutropenia often requiring dose reductions and treatment delays. We describe the use of granulocyte colony-stimulating factor (G-CSF) in three patients in order to maintain the treatment schedule. A subcutaneous injection of 5 micrograms/kg/day was administered on Days 3-6 and 9-14 of each chemotherapy cycle. No patients had any adverse effects and all received full chemotherapy doses without any treatment delay. The addition of G-CSF to the EMA/CO regimen may benefit patients by achieving dose intensity in the treatment of high-risk gestational trophoblastic disease.

Gray scale and color flow Doppler characterization of uterine tumors.

The aim of this study was to investigate gray scale and color flow characteristics of a group of patients with a suspected uterine pathologic condition. One hundred and twenty-two consecutive patients at the Women's Cancer Center, University of Minnesota, undergoing transvaginal sonography and color flow Doppler imaging for suspected uterine corpus abnormality made up the study group. After gray scale morphologic assessment, color flow Doppler imaging of the tumor and uterus was performed, including the ipsilateral uterine artery. Malignant tumors were confirmed pathologically in all 35 patients who had them. In comparing patients with benign versus malignant tumors, gray scale morphologic assessment confirmed that malignant uterine tumors (31 endometrial cancers and four sarcomas) were more likely to have a thickened echoic endometrium (P = < 0.0001), be enlarged (P = 0.004), to be retroverted (P = 0.02), and to lack a subendometrial halo (P < 0.0001). Patients with four benign and 13 malignant tumors demonstrated increased flow when assessed by CFD. The calculated sensitivity of increased color flow in predicting malignancy was 39%, with a specificity of 92%, a positive predictive value of 77%, and a negative predictive value of 71%. No difference existed between the benign and malignant groups for the systolic, diastolic, and mean velocities and for the calculated pulsatility index and resistive index in both sampled uterine and intramyometrial or tumor vessels.(ABSTRACT TRUNCATED AT 250 WORDS)

Pelvic adhesion formation after pelvic lymphadenectomy: comparison between transperitoneal laparoscopy and extraperitoneal laparotomy in a porcine model.

Compared to extraperitoneal laparotomy, the transperitoneal approach is associated with increased enteric morbidity. Recently, transperitoneal laparoscopy has been employed as a method to surgically stage patients with gynecologic malignancies. The objective of this study was to investigate pelvic adhesion formation in a porcine model after pelvic lymphadenectomy performed via transperitoneal laparoscopy (LS) compared to extraperitoneal laparotomy (EP). Ten adult, female hogs underwent LS and 10 underwent EP. A complete pelvic lymphadenectomy was performed in each animal. Three weeks after the lymphadenectomy, the animals underwent exploratory laparotomy, and the adhesions were quantified. Nineteen animals were evaluable. The adhesion scores for the laparoscopy group (N = 10, mean = 0.075 +/- 0.17) were not statistically different from those of the laparotomy group (N = 9, mean = 0.28 +/- 0.52, P > 0.5). Eight of 10 (80%) and 5 of 9 (56%) animals in the LS and EP groups, respectively, had no adhesions after pelvic lymphadenectomy. Adhesion formation is one of many critical issues concerning the utility of pretreatment surgical staging, especially for cancer of the cervix. It is remarkable that only 20% of the animals undergoing laparoscopy in this study had de novo adhesions after pelvic lymph node dissection and that the mean total adhesion score was not statistically different from the extraperitoneal laparotomy. Therefore, transperitoneal laparoscopic pelvic lymphadenectomy may not induce the degree of adhesion formation associated with the transperitoneal laparotomy technique.

Local anesthesia for cryosurgery on the cervix.

Forty-five patients were evaluated in a prospective, randomized study to determine the effectiveness of a local injection of lidocaine in reducing pain during cervical cryosurgery. Study patients received a submucosal cervical injection of 1% lidocaine with a 1:100,000 dilution of epinephrine. Control patients did not receive an injection. Both groups received a single dose of naproxen sodium or ketoprofen prior to the procedure. The patient and the observing nurse recorded the pain experienced with a visual analog scale (VAS). Nurse and patient response for the control and study groups showed a high correlation (r = .573 and P < .01, r = .673 and P < .001, respectively). The mean VAS score recorded for the 26 control patients was 4.27, significantly greater than the mean score for the 19 study patients, 1.16 (P < .001). These findings indicate that a submucosal local injection of lidocaine with epinephrine is effective in reducing pain during cervical cryosurgery.