A 10-year review of primary fallopian tube cancer at a community hospital: a high association of synchronous and metachronous cancers.

Primary fallopian tube carcinomas (PFTC) are rare gynecological tumors infrequently diagnosed prior to operative intervention. A retrospective review was performed to characterize the distribution and clinicopathologic significance of these tumors. Identification of PFTC was achieved through a review of the tumor registry and medical record ICD-9 codes at a community teaching hospital. A total of 1.5% of all gynecological cancers were PFTC. Most patients were presumed to have ovarian cancer. Ultrasound had the highest sensitivity (82%) for preoperative diagnosis. Surgical exploration was needed for definitive diagnosis in all patients. Optimal debulking was predictive of survival and of a negative second-look laparotomy (P < 0.05). Twenty-five percent of patients had a metachronous cancer diagnosed prior to their fallopian tube cancer, and 22% had a synchronous gynecological malignancy diagnosed at the time of surgical exploration. The response rate to platinum-based chemotherapy was 78%. The 5-year survival rate was 87%, and the overall survival rate was 75%. The median follow-up was 38 months. This report details the diagnostic and therapeutic experience of patients with PFTC and describes the occurrence of synchronous and metachronous gynecological cancers.

Tumor board in gynecologic oncology.

OBJECTIVE: This study evaluates the influence of a weekly tumor conference on the management of patient care in a gynecologic oncology service. METHODS: The study utilizes all patients discussed in the gyncologic oncology tumor conference at the University of Texas Medical Branch (UTMB) from January 1, 1998, to January 1, 2001. Patient's information (age, race, cancer site, stage, new cancer versus recurrent) was abstracted from the minutes and attendant log of the tumor board. We compared the pathology and diagnosis for each patient as stated both before and after presentation at the tumor board. A discrepancy is defined as a change in tumor site, stage, or treatment, resulting from findings discussed at tumor board meetings. Major discrepancy is defined as changes that affect patient care. Minor discrepancy is defined as changes that do not affect patient care. RESULTS: During the study period, a total of 459 cases were discussed (391 new cancer, 68 recurrent cancer). At each tumor conference, we discussed a mean of 3.7 cases (range 1-9, standard deviation 1.68). Thirty-two cases (6.9%) showed discrepancies with 23 major discrepancies and nine minor discrepancies. As a result of the tumor board, the two most common therapeutic changes were the addition of chemotherapy and surgery. CONCLUSIONS: In this study, a gynecologic oncology tumor board added clinical information available to pathologists, thereby alters final diagnosis and affects patient medical care.

Phase II trial of oral altretamine for consolidation of clinical complete remission in women with stage III epithelial ovarian cancer: a Southwest Oncology Group trial (SWOG-9326).

OBJECTIVE: The aim of this study was to evaluate the 2-year survival rate in a group of women in complete clinical remission (cCR) from Stage III ovarian cancer following front-line therapy who were then treated with a 6-month course of altretamine. METHODS: Patients were documented to be in cCR by physical examination, computed tomography or magnetic resonance imaging scan, and serum CA-125. Treatment consisted of altretamine (Hexalen) 260 mg/m(2)/day po divided into four doses taken after meals and at bedtime for 14 of 28 days for six cycles. Based on previous experience in the Southwest Oncology Group, the treatment would be considered promising if the 2-year survival rate was > or = 65% as measured from study registration. RESULTS: From 9/1/93 and 7/1/97, 112 patients were registered and 97 were fully evaluable. The majority of patients had optimally debulked (< or = 1 cm: 63%), high-grade (Grade 3: 82%) tumors. The 2-year survival rate in this study was 75% (95% CI: 66-84%). For those patients with optimal disease, the 2-year survival rate was 82% (95% CI: 72-92%) and for those with suboptimal disease it was 64% (95% CI: 48-79%). Four patients (4%) experienced Grade 4 and 21 patients (22%) experienced Grade 3 toxicities consisting primarily of nausea/vomiting, neutropenia, fatigue, anxiety, and paresthesias. CONCLUSIONS: The 2-year survival rate in this study warrants further evaluation of consolidation therapy for women in clinical complete remission following front-line chemotherapy for Stage III ovarian cancer. Caution is advised in the interpretation of these data, however, because of the nonrandomized nature of the trial and the unknown contribution of front-line use of paclitaxel to the durability of clinical complete response.

Surgical blood loss in abdominal hysterectomy.

OBJECTIVE: The aim of this study was to evaluate additional error in estimating red cell loss during abdominal hysterectomy. METHODS: Eighty patients admitted consecutively for abdominal hysterectomy were recruited. The surgeries were done after heparinizing the suction tubing system to prevent clotting and reducing the vacuum pressure to reduce red cell lysis. At the end of the surgery, hematocrit was measured and compared with the patient's venous blood and the blood from the suction container. The Mann-Whitney test evaluated statistical significance. RESULTS: Eight patients were excluded for having a hemolyzed blood sample, receiving a blood transfusion, and having incomplete data. The study cohort consisted of 72 patients: 54 had a simple hysterectomy and 18 had a radical hysterectomy with pelvic and periaortic lymphadenectomy. The hematocrit (mean +/- standard deviation) in the suction container (19.8 +/- 8.8%) was lower than the hematocrit from the venous blood sample (32.4 +/- 6%) (P < 0.001). The hematocrit in the suction container decreased as the duration of the surgeries increased. Although the volume of blood in the suction container was used to estimate blood loss, the concentration of red cells in the container was consistently lower than those in the venous blood sample. The magnitude of dilution increased as the length and radical nature of the surgery increased. CONCLUSIONS: These findings suggest that other fluid, probably lymph, contributes to the dilution of red cells in the container and increases the estimated blood volume loss during surgery. Estimation of red cell surgical blood loss becomes less accurate as the length and radical nature of the surgery increase.

Effect of hemodilution on tissue perfusion and blood coagulation during radical hysterectomy.

OBJECTIVE: The goal of this study was to evaluate the safety of hemodilution on global and splanchnic perfusion and blood coagulation during radical hysterectomy. METHODS: A pulmonary artery catheter and a gastric tonometry catheter were placed in 16 patients with cervical carcinoma. Global perfusion indices, splanchnic perfusion index, and coagulation tests were obtained. Blood was removed to achieve a hemoglobin measurement of 8-9 9 g/dL. Three more measurements were repeated after hemodilution, at the end of surgery, and after the retransfusion of blood. Analysis of variance was used to determine statistical significance. RESULTS: Sixteen patients with cervical carcinoma had 1.0 +/- 0.3 L (mean +/- SD) of blood removed and had a blood loss of 0.8 +/- 0.7 L. Hemodiluted preoperative hemoglobin was 8.7 +/- 1 g/dL. All of the global perfusion indices, except for arterial pH and oxygen consumption, decreased after hemodilution and recovered with the retransfusion of blood (P < or = 0.004). Splanchnic perfusion and coagulation tests were unchanged (P > or = 0.1). Major complication was pulmonary edema in one patient. CONCLUSION: Hemodilution during radical hysterectomy, in this select group of patients, does not appear to compromise tissue perfusion or coagulation.

Human papillomavirus testing for triage in a referral population.

OBJECTIVE: This study evaluated the Digene HPV Assay Hybrid Capture System(R) as a triage method. METHODS: Results of an HPV assay were compared with a final tissue diagnosis of cervical intraepithelial neoplasia 2 (CIN2) or greater. These results were stratified based on Pap smear diagnosis and evaluated in 4 triage algorithms. RESULTS: Of the 4 algorithms evaluated, the highest savings came from not performing colposcopy for patients with repeat atypical squamous cells of undetermined significance (ASCUS), but that resulted in missing nine patients with CIN2 and CIN3 histology. HPV testing failed to diagnose 67% (6 out of 9) to 48% (10 out of 21) of patients with underlying CIN2 and CIN3. CONCLUSIONS: Although HPV high-risk positive results correlate with high-grade histology, it is associated with significant false negatives. The HPV low-risk test is not clinically useful. These tests were poor methods to triage patients in our population.

Lower genital tract metastases of placental site trophoblastic tumor: case report and review of the literature.

OBJECTIVES: We present a case of metastatic placental site trophoblastic tumor (PSTT) and review the English literature on this entity. MATERIALS AND METHODS: In addition to the case presentation, literature review describes 23 additional cases with differing treatments and length of survival. RESULTS: The patient is free of disease more than 5 years after diagnosis. She received multimodality treatment including surgery, chemotherapy, and radiotherapy. Eleven other patients survived the disease from 12 to 36 months after initial diagnosis. CONCLUSION: Metastatic PSTT has a poor prognosis and requires aggressive treatment. ▪.

Phase II trial of oral etoposide in recurrent or refractory endometrial adenocarcinoma: a southwest oncology group study.

Oral etoposide has activity in a wide variety of tumors and is well tolerated. Therefore, the efficacy of oral etoposide was assessed as a treatment of metastatic endometrial cancer. To be eligible for this group-wide Southwest Oncology Group trial, patients had to have histologically proven metastatic or recurrent endometrial carcinoma; no previous cytotoxic therapy; and adequate renal, hepatic, and hematologic function, and they had to have given informed consent. Therapy consisted of oral etoposide, 50 mg daily on days 1-21 on a 28-day schedule. Therapy was continued in the absence of toxicity or disease progression. Forty-four eligible women, with a median age of 68 years (range 38-84 years) were treated. Radiotherapy had been delivered to 33 and hormomal therapy to 21. The median duration of therapy was 69 days (range 7-510 days). The treatment was well tolerated. Only one patient had grade 4 neutropenia, and a second had grade 4 anemia. Three patients had grade 3 nausea. One complete and five partial responses (14%) were observed. An additional four patients had unconfirmed responses. Tumor regressions were noted in nodes, bone, and visceral organs. While oral etoposide has only a modest level of activity when used in chemonaive patients, the minimal toxicity of this drug makes it a candidate for use in combination chemotherapy.

Oncogene expression and microvessel count in recurrent and nonrecurrent stage Ib squamous cell carcinoma of the cervix.

OBJECTIVE: To evaluate p53, epidermal growth factor receptor (EGFR) and c-erbB-2 oncogene expression and compare it with microvessel count (MVC) in determining the clinical outcome of stage Ib squamous cell carcinoma (SCC) of the cervix. STUDY DESIGN: Immunostaining with p53, EGFR, C-erbB-2 and factor VIII antibodies was performed on tumor sections from 22 patients (11 with cancer recurrence, 11 free of cancer after four years). The levels of oncogene expression were semiquantitatively graded (0-4). Microvessels were counted (per 200 x field) in areas of highest neovascularization. RESULTS: Eight of 11 patients (72.7%) with recurrence expressed EGFR as compared with 5 of 11 patients (45.5%) free of disease. This difference is not significant (P = .39). An equal number of patients with and without recurrence expressed c-erbB-2. Five of 11 patients (45.5%) with recurrence expressed p53, as compared with 6 of 11 (54.5%) free of disease (P = 1.00). Eight of 11 patients (72.7%) with recurrence had an MVC above 24 as compared with 2 of 11 patients (18.2%) free of disease; this difference was statistically significant (P = .03). CONCLUSION: The expression of EGFR, p53 and c-erbB-2 appears to have little prognostic value in stage Ib SCC of the uterine cervix. The prognostic value of MVC is in keeping with previous findings.

Randomized comparison of fluorouracil plus cisplatin versus hydroxyurea as an adjunct to radiation therapy in stage IIB-IVA carcinoma of the cervix with negative para-aortic lymph nodes: a Gynecologic Oncology Group and Southwest Oncology Group study.

PURPOSE: In 1986, a protocol comparing primary radiation therapy (RT) plus hydroxyurea (HU) to irradiation plus fluorouracil (5-FU) and cisplatin (CF) was activated by the Gynecologic Oncology Group (GOG) for the treatment of patients with locally advanced cervical carcinoma. The goals were to determine the superior chemoradiation regimen and to quantitate the relative toxicities. METHODS: All patients had biopsy-proven invasive squamous cell carcinoma, adenocarcinoma, or adenosquamous carcinoma of the uterine cervix. Patients underwent standard clinical staging studies and their tumors were found to be International Federation of Gynaecology and Obstetrics stages IIB, III, or IVA. Negative cytologic washings and para-aortic lymph nodes were required for entry. Patients were randomized to receive either standard whole pelvic RT with concurrent 5-FU infusion and bolus CF or the same RT plus oral HU. RESULTS: Of 388 randomized patients, 368 were eligible; 177 were randomized to CF and 191 to HU. Adverse effects were predominantly hematologic or gastrointestinal in both regimens. Severe or life-threatening leukopenia was more common in the HU group (24%) than in the CF group (4%). The difference in progression-free survival (PFS) was statistically significant in favor of the CF group (P = .033). The sites of progression in the two treatment groups were not substantially different. Survival was significantly better for the patients randomized to CF (P = .018). CONCLUSION: This study demonstrates that for patients with locally advanced carcinoma of the cervix, the combination of 5-FU and CF with RT offers patients better PFS and overall survival than HU, and with manageable toxicity.

Papanicolaou smears of atypical glandular cells of undetermined significance: histological correlations and suggestions for management.

OBJECTIVE: We sought to correlate cervical and endometrial neoplasias with Papanicolaou (Pap) smears of atypical glandular cells of undetermined significance (AGUS) and to suggest management. MATERIALS AND METHODS: One hundred seventy-one patients with AGUS Pap smears were followed prospectively with colposcopy, biopsies, endocervical curettage, and endometrial biopsies. RESULTS: One hundred twelve patients (65%) with AGUS Pap smears favoring reactive changes were found to harbor 13 preinvasive and invasive cervical squamous neoplasias and 1 ovarian sarcoma (total, 12.5% of patients with smears). Fifty-nine patients (35%) with AGUS Pap smears favoring neoplastic changes harbored 25 preinvasive and invasive squamous and glandular cervical and endometrial neoplasias (42.3%). CONCLUSION: In the presence of an AGUS Pap smear favoring reactive changes, colposcopy, biopsies, and endocervical curettage should be performed. Endometrial biopsy should be added when AGUS Pap smear favors neoplasia.

Dermatofibrosarcoma protuberans of the vulva: report of two new cases and review of the literature.

BACKGROUND: Dermatofibrosarcoma protuberans (DFSP), a low-grade sarcoma of dermal origin, rarely is found on the vulva. Only 16 cases of DFSP of the vulva have been described. CASES: Two patients with long histories of primary vulvar dermatofibrosarcoma protuberans are presented. Both required multiple excisions to resect the tumor completely. The patients remain without evidence of disease after long-term follow-up. One patient is among the youngest recorded. All published cases of vulvar DFSP are reviewed. CONCLUSIONS: Both our experience and that reported in previous cases indicate that wide local excision is required in the treatment of vulvar DFSP.

Circulating serum levels of cytokines and angiogenic factors in patients with cervical cancer.

Progression of cervical cancer is associated with excessive circulating levels of cytokines, which are known to be modulators of tumor angiogenesis. The concentrations of cytokines and growth factors were assayed using enzyme-linked immunosorbant assays in the serum of 61 women in various stages of cancer [stage 0 (n = 6), stage I (n = 15), stage II (n = 15), stage III (n = 15), and stage IV (n = 10)] and of 20 healthy control subjects. Our results indicated that b-FGF and TNF-beta levels were significantly elevated in stage I, and serum levels of TGF-beta and IL-7 were elevated in stages II-IV of invasive carcinoma. Our experimental subjects had significantly increased serum levels of IL-6, GM-CSF, and angiogenin in stages I-IV of cervical cancer, and TNF-alpha serum levels were elevated in all stages of invasive carcinoma. The serum levels of IL-8 and IL-10 were elevated only in stages II-III, and the levels of IL-2 were elevated in stages III-IV. The serum levels of IL-1 alpha and IL-1 beta remained unaltered in all stages of cancer progression. Progression of cervical cancer is associated with increased serum levels of angiogenin, IL-2, IL-6, IL-7, IL-8, IL-10, b-FGF TNF-alpha, TGF-beta, TNF-beta, and GM-CSF during different stages, all of which have the potential to be angiogenic amplifiers.

Conservative management of positive resection margins after loop electrosurgical excision procedure.

OBJECTIVES: We sought to determine the pres-ence of residual neoplasia in women reported previously as having positive surgical margins after loop electrosurgical excision procedure of the cervix. METHODS: Of 460 loop electrosurgical excision procedures of the cervix, 127 (27.6%) had margins positive for cervical intraepithelial neoplasia. We re-viewed the charts of 74 patients (58%). We found positive en-docervical margins in 68 of 74 (92%) and positive ectocervical margins in 4 of 74 (5%). In 2 of 74 (3%), the location of the positive margin was unknown. Patients were followed either with three consecutive Papanicolaou smears (n = 43) during the year after the procedure or with conization or hysterec-tomy (n = 31). RESULTS: The overall rate of spontaneous regression of cervical intraepithelial neoplasia was 64%. The small study sample does not permit us to conclude whether either positive ectocervical or endocervical margins were more amenable to recurrence. No invasive cancer was diagnosed in the study. CONCLUSIONS: With a reliable patient population, patients with cervical margins positive for cervical intraepithelial neoplasia after loop electrosurgical excision procedure can be followed safely with cytology.

Management of cervical intraepithelial neoplasia during pregnancy: a simplified and cost-effective approach.

OBJECTIVES: To determine the cost-effectiveness of managing an abnormal Papanicolaou (PAP) smear during pregnancy with a single colposcopic exam and biopsies, followed by Pap smears in each subsequent trimester of pregnancy and 8 weeks postpartum. MATERIALS AND METHODS: We reviewed 84 pregnant women with cervical intraepithelial neoplasia (CIN) between 1983 and 1991, testing the accuracy of an initial biopsy and subsequent Pap smears, to follow the progression (or regression) of disease as determined by postpartum biopsy or Pap smears. RESULTS: In 26 women with CIN1, 2 (8%) progressed to CIN3. In 29 women with CIN2, 5 (17%) progressed to CIN3. Of 29 patients with CIN3, 20 (69%) remained at CIN3 and 2 (6%) progressed to microinvasive carcinoma postpartum, confirmed by conization. No invasive carcinoma was missed. The cost of colposcopy with biopsies and Pap smear is $304, whereas cost of a Pap smear only is $30. CONCLUSIONS: Single colposcopy with biopsies at the beginning of pregnancy and Pap smears during subsequent trimesters and postpartum should be adequate follow-up to prevent progression to invasive cancer and represents a significant cost savings.

Three-dimensional endothelial-tumor epithelial cell interactions in human cervical cancers.

The purpose of this study is to understand the multicellular interaction between tumor epithelial (TEC) and human umbilical vein endothelial cells (HUVEC). The development of in vitro systems in which to coculture these cells as multicellular aggregates is very critical. Cell lines were established from cervical tumor cells (n = 6) and two from HUVEC (n = 2) and they were cultured as three-dimensional (3-D) multicellular-cultures using Cytodex-3 microcarrier beads in the rotating wall vessel (RWV). After a 240-h incubation, TEC and HUVEC proliferated exponentially to 4.2 x 10(7) and 2.2 x 10(7) cells/ml, respectively, without requiring a feeder layer; in contrast to the two-dimensional (2-D) cultures that average about 8 x 10(5) cells/ml. Phase contrast microscopy indicated formation of 3-D aggregates that varied in size from 0.5 to 5 mm. The size of the aggregates (1-5 mm, 6-14 microcarriers) increased over time; however, the number of aggregates (0.5-1 mm, 2-5 microcarriers) decreased over a long-term incubation (240 h) because the cells merged to form large clumps. Maximum aggregation was observed with TEC at 120 h and HUVEC at 96 h. The culture of TEC in the absence of HUVEC produced minimal differentiation in contrast to cocultures. The TEC and HUVEC as cocultures in RWV proliferated at an accelerated rate (1.3 x 10(7) cells/ml, 96 h). The TEC-HUVEC coculture presented tubular structures penetrating the tumor cell masses, forming aggregates larger in size than the monocultures and typically with greater cell mass and number. The cells were viable (trypan blue exclusion) and metabolically active (glucose utilization) until 240 h. These data suggest that RWV provides a new model that allows us to investigate the regulatory factors that govern tumor angiogenesis.

Flow cytometry in cervical adenocarcinoma. Correlating DNA content analysis with the clinical picture.

OBJECTIVE: DNA quantitation by flow cytometry was used in this study to determine prognosis in stage I adenocarcinoma of the uterine cervix with negative pelvic lymph nodes. STUDY DESIGN: DNA content and proliferation index were determined by flow cytometry on formalin-fixed, paraffin-embedded tissue from 29 patients with stage I, pelvic lymph node-negative adenocarcinoma of the cervix. Using Student's t test, the results were correlated with tumor recurrence after 57 +/- 8 months. RESULTS: Diploid DNA content predominated (79%), whereas only 21% of the tumors were aneuploid. There was recurrence of the tumor in five cases (17%); two tumors were aneuploid, and three were euploid. The recurrence rate among the aneuploid population of 33% (2 of 6) was not statistically significant as compared to 13% (3 of 23) in the diploid population (P > .2). Similarly, the mean proliferation index (percentage in S plus G2/M phases) of the tumors in patients with recurrence was 13.7 +/- 3.68%, which was not significantly different from those that did not recur (mean 15.6 +/- 3.49%). CONCLUSION: DNA content analysis and proliferative activity do not predict recurrence in stage I, pelvic lymph node-negative adenocarcinoma of the uterine cervix.

Serum levels of interleukins, growth factors and angiogenin in patients with endometrial cancer.

The purpose of this work was to study changes in serum levels of interleukins, growth factors and angiogenin during different stages of endometrial cancer progression. Serum levels were assayed by enzyme-linked immunosorbant assay in 59 women with stages I-IV of endometrial cancer (study subjects: stage I, n = 20; stage II, n = 8; stage III, n = 5; stage IV, n = 6) and compared to the serum levels in 20 women without cancer as control subjects. Patients with endometrial cancer had varied serum levels of interleukins and growth factors. There was a significant increase in serum levels of angiogenin in all stages of tumor progression. Levels of interleukin-8 (IL-8), IL-10 and transforming growth factor beta (TGF beta) were significantly elevated in patients with stages I and II carcinoma. The serum levels of tumor necrosis factor alpha (TNF alpha), granulocyte/macrophage-colony-stimulating factor, basic fibroblast growth factor (BFGF), IL-7 and IL-2 were significantly elevated in patients with stages II and III carcinoma and the serum level of tumor necrosis factor beta (TNF beta) was slightly elevated in patients with stage II carcinoma only. The serum levels of IL-1 alpha, IL-1 beta and IL-6 were not elevated in endometrial cancer patients in any of the clinical stages. The results showed that progression of endometrial cancer is associated with increased serum levels of cytokines, growth factors and angiogenin, which possibly amplify angiogenesis during different clinical stages.

Intraperitoneal cisplatin plus intravenous cyclophosphamide versus intravenous cisplatin plus intravenous cyclophosphamide for stage III ovarian cancer.

BACKGROUND: Intravenous platinum-based chemotherapy is the standard primary therapy for advanced ovarian cancer. We conducted a phase 3 trial to compare the effects of intraperitoneal and intravenous cisplatin on the survival of women with previously untreated, stage III, epithelial ovarian cancer. METHODS: The patients underwent an initial exploratory laparotomy and resection of all tumor masses larger than 2 cm. Within four weeks after surgery, six courses of intravenous cyclophosphamide (600 mg per square meter of body-surface area per course) plus either intraperitoneal cisplatin (100 mg per square meter) or intravenous cisplatin (100 mg per square meter) were administered at three-week intervals. RESULTS: Of 654 randomized patients, 546 were eligible for the study. The estimated median survival was significantly longer in the group receiving intraperitoneal cisplatin (49 months; 95 percent confidence interval, 42 to 56) than in the group receiving intravenous cisplatin (41 months; 95 percent confidence interval, 34 to 47). The risk of death was lower in the intraperitoneal group than in the intravenous group (hazard ratio, 0.76; 95 percent confidence interval, 0.61 to 0.96; P = 0.02). Moderate-to-severe tinnitus, clinical hearing loss, and neuromuscular toxic effects were significantly more frequent in the intravenous group. CONCLUSIONS: As compared with intravenous cisplatin, intraperitoneal cisplatin significantly improves survival and has significantly fewer toxic effects in patients with stage III ovarian cancer and residual tumor masses of 2 cm or less.