Ureteroarterial fistula.

The authors intended to perform a comprehensive review of the literature pertaining to ureteroarterial fistulae and apply the findings to a case. A comprehensive literature search was performed using the Keywords: ureter, artery and fistula. The available articles printed in or translated to English were analysed for overall trends. The results were then compared with the case of a patient (index patient). Review of the literature reveals that 57% of all ureteroarterial fistulae form in women at an average age of 58. The most common presenting complaint is haematuria. There appears to be a shift in management from primarily open surgical to primarily angiographic. The known risk factors are: vascular pathology, malignancy, prior radiation and indwelling stents. While 98% of all cases have at least one known risk factor, only 41% had two or more. We report an additional case of this rare condition, and review the present literature.

Growth hormone-releasing hormone antagonists inhibit growth of human ovarian cancer.

Epithelial ovarian carcinoma is the leading cause of cancer-related deaths among women with gynecologic malignancies. Antagonists of the growth hormone-releasing hormone (GHRH) have been shown to inhibit growth of various cancers through endocrine, autocrine, and paracrine mechanisms. In this study, we have investigated the effects of GHRH antagonists (GHRHa) in ES-2 human clear cell ovarian cancer and in UCI-107 human serous ovarian cancer in vitro and in vivo. We evaluated the expression of mRNA for GHRH receptor, the binding to GHRH receptors, in specimens of ES-2 ovarian cancer. We evaluated also the in vitro effects of GHRHa on ES-2 cells and the in vivo effect of 2 different GHRHa on ES-2 and UCI-107 tumors. Nude mice bearing xenografts on ES-2 and UCI-107 ovarian cancer were treated with JMR-132 and MZ-J-7-118, respectively. Tumor growth was compared to control. ES-2 cells expressed mRNA for the functional splice variant SV1 of the GHRH receptor. JMR-132 inhibited cell proliferation in vitro by 42% and 18% at 10 and 1 µM concentration, respectively. Specific high affinity receptors for GHRH were detected in ES-2 cancer samples. In vivo daily subcutaneous injections of GHRHa significantly reduced tumor growth compared to a control group in both animal models. Our results indicate that GHRHa such as JMR-132 and MZ-J-7-118 can inhibit the growth of human ovarian cancer. The efficacy of GHRHa in ovarian cancer should be assessed in clinical trials.

A phase II trial of pyrazoloacridine (PZA) in squamous carcinoma of the cervix--a Gynecologic Oncology Group Study.

PURPOSE: The Gynecologic Oncology Group performed a Phase II study to determine the response rate of Pyrazoloacridine (PZA) in patients with advanced, persistent or recurrent squamous carcinoma of the cervix. METHODS: PZA was administered at a dose of 750 mg/m2 intravenously over three hours every three weeks. RESULTS: Among 21 evaluable patients, there were no complete and one (4.2%) partial response. The major toxicities were hematologic. CONCLUSION: PZA at the dose and schedule employed has insignificant activity in this population.

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.

Prognostic nutritional index in relation to hospital stay in women with gynecologic cancer.

OBJECTIVE: To estimate the prevalence of malnutrition, correlate it with length of hospital stay, and evaluate laboratory tools to define it in gynecologic oncology. METHODS: Sixty-seven consecutive hospitalized gynecologic oncology patients were evaluated prospectively using the standardized Prognostic Nutritional Index method, based on serum albumin, transferrin, triceps skin fold and skin sensitivity tests, which defines criteria for malnourished and nourished patients. It was correlated with length of hospital stay. The Mann-Whitney test and Pearson's correlation coefficient were used to evaluate statistical relationships. RESULTS: Cancer distribution among study subjects was 39 cervical (58%), 16 uterine (24%), 11 ovarian (16%), and one vulvar (2%). Malnutrition was found in 36 of 67 women (54%; 95% confidence interval [CI] 41%, 66%). The median (interquartile range) hospital stays of nourished women (n = 31) and malnourished women (n = 36) were 6 (range 4-7) days and 8 (range 6-16) days, respectively (two-sided P =.004). That difference remained after controlling for age, extent of metastases, and cancer sites. Albumin correlated well with Prognostic Nutritional Index (R = -.78; 95% CI -.86, -.66; P <.001). Albumin also correlated with length of hospital stay R = -.41; 95% CI -.56, -.25; P <.001). CONCLUSION: Malnutrition is common in gynecologic oncology patients and contributes to longer hospital stays. Albumin is a good substitute for the Prognostic Nutritional Index laboratory test for assessing malnutrition.

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. ▪.

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.

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.

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.

Does glutamine supplementation increase radioresistance in squamous cell carcinoma of the cervix?

OBJECTIVE: Glutamine is proposed to protect bowel from radiation. However, glutamine may decrease cancer's radiosensitivity. We evaluate glutamine's effect on the growth rate and radiosensitivity of two cervical carcinoma cell lines in vitro. METHODS: HeLa and CaSki cells were seeded at 3000 cells/well in glutamine-free medium. An increasing amount of glutamine (0.4, 10, and 20 mM) was added to the respective plates, incubated, and irradiated with a single fraction of 0.5, 1, 3, and 6 Gy. Using a growth inhibition assay and photometric analysis, the viable cells were counted on day 8. Cell counts represent a mean +/- standard deviation from six experiments and are expressed in 10(3) cells. Analysis of variance was performed. RESULTS: In nonirradiated HeLa plates, absence of glutamine results in 5.7 +/- 1.2 cells/well. Addition of glutamine at 0.4, 10, and 20 mM to nonirradiated cells significantly (P < 0.0001) increased growth to 79.1 +/- 10.0, 122.5 +/- 9.0, and 114.3 +/- 13.9 cells/well, respectively. In culture plates irradiated with 6 Gy, HeLa cells supplemented with 0.4, 10, and 20 mM of glutamine showed lower cell counts (P < 0.008). A similar significant growth suppression at 6 Gy in comparison to 0.5, 1, and 3 Gy was observed (P < 0.01). CaSki cells showed similar patterns. CONCLUSIONS: Growth of HeLa and CaSki cells in vitro requires a minimum of 0.4 mM of glutamine in the medium. Supraphysiologic glutamine concentration does not increase tumor growth or radioresistance. Glutamine should be evaluated further as a potential bowel radioprotector.

A phase II trial of amonafide in patients with nonsquamous cell carcinoma of the cervix. A Gynecologic Oncology Group study.

Twenty-seven patients with nonsquamous cell carcinoma of the cervix were entered into a Phase II study of amonatide; 24 patients were evaluable for toxicity, while 23 were evaluable for response. Patients received amonafide, 300 mg/m2, intravenously for 5 consecutive days every 3 weeks. The median age of patients was 45 years. All but two patients were completely ambulatory. Twelve patients had received prior chemotherapy, while 22 had been treated with radiation therapy. One of 27 (4.3%) patients had a partial response (PR) to this regimen and 13 (56.5%) had stable disease. Sixteen patients experienced a median white blood cell (WBC) nadir of 350/mm3, seven developed life-threatening thrombocytopenia, and one had severe anemia requiring transfusion. Nonhematologic toxicity was mild. Amonafide had insignificant activity in these patients with nonsquamous cell carcinoma of the cervix.

Benign adrenal cyst presenting in a pregnant patient.

Cystic lesions of the adrenal gland are uncommon, most often diagnosed incidentally during diagnostic imaging or autopsy. An adrenal cyst presenting as a pelvic mass in pregnancy offers the clinician a diagnostic and therapeutic dilemma. A 28-year-old black female presented for routine obstetric care at 26 weeks' gestation and was found on examination to have a 40-cm pelvic-abdominal mass. Ultrasound confirmation revealed the mass to be cystic and arising from the right pelvis. Laboratory tests including hematocrit, white blood cell count, electrolytes, rapid plasma reagin (RPR), and CA-125 were within normal limits. The patient underwent exploratory laparotomy and a 40 x 20 cm right adrenal cyst was identified and resected. Postoperatively, the patient developed preterm labor and delivered a 955-g infant; the infant was discharged home 3 months later with bronchopulmonary dysplasia and delayed developmental milestones. The woman was discharged home without complication on postoperative Day 8. Accurate preoperative determination of the origin of a pelvic mass occurring in pregnancy is helpful in timing therapeutic intervention. Use of ultrasound and magnetic resonance imaging (MRI) modalities can provide detailed anatomical information without risk to mother or fetus. Conservative management of adrenal cyst in pregnancy may lower the morbidity and mortality of the mother and fetus.

Adenovirus-based p53 gene therapy in ovarian cancer.

Mutations of the p53 tumor suppressor gene are the most common molecular genetic abnormality to be described in ovarian cancer. To determine the feasibility of mutant p53 as a molecular target for gene therapy in ovarian cancer, we constructed an adenovirus vector containing the wild-type p53 gene. The ability of this adenovirus construct (Ad-CMV-p53) to express p53 protein was examined by Western blot analysis in the H358 lung cancer cell line, which has a homozygous deletion of the p53 gene. The ability of the adenovirus vector system to infect ovarian cancer cells was tested using an adenovirus containing the beta-galactosidase reporter gene under the control of the CMV promoter (Ad-CMV-beta gal). The ovarian cancer cell line 2774, which contains an Arg273His p53 mutation, was infected with Ad-CMV-beta gal, and the infected cells were assayed for beta-galactosidase activity after 24 hr. To test the ability of wild-type p53 to inhibit cell growth, the 2774 cell line was infected with Ad-CMV-p53 or Ad-CMV-beta gal, and the effect of these agents on the growth of 2774 cells was determined using an in vitro growth inhibition assay. Western blot analysis of lysates from H358 cells infected with Ad-CMV-p53 showed expression of wild-type p53 protein. When 2774 cells were infected with Ad-CMV-beta gal at a multiplicity of infection (m.o.i.) of 10 PFU/cell, > 90% of cells showed beta-galactosidase activity, demonstrating that these cells are capable of efficient infection by the adenovirus vector. Growth of 2774 cells infected with Ad-CMV-p53 was inhibited by > 90% compared to noninfected cells. The ability of the adenovirus vector to mediate high-level expression of infected genes and the inhibitory effect of Ad-CMV-p53 on the 2774 cell line suggests that the Ad-CMV-p53 could be further developed into a therapeutic agent for ovarian cancer.

A phase II trial of neoadjuvant chemotherapy prior to radical hysterectomy and/or radiation therapy in the management of advanced carcinoma of the uterine cervix.

OBJECTIVE: This prospective trial was designed to access the efficacy and safety of neoadjuvant chemotherapy followed by radical hysterectomy and/or radiation therapy in women with advanced carcinoma of the uterine cervix. METHODS: Thirty women, clinical stages IIb-IVa, were enrolled in this clinical trial. Initial treatment consisted of three cycles of bleomycin, cisplatin, and vincristine administered every 10 days. Depending on the extent of disease after chemotherapy, patients then either underwent radical hysterectomy with bilateral pelvic and periaortic lymphadenectomy or surgical staging. Following review of the surgical findings, tailored radiotherapy was administered. RESULTS: Only 10 women (34%) had tumor regression from neoadjuvant chemotherapy sufficient to allow radical hysterectomy prior to tailored adjuvant radiotherapy; the remainder received primary radiotherapy after surgical staging. Two-year disease-free survival was 68, 43, and 0% for women with clinical stages II, III, and IV, respectively. Four women experienced acute toxicity from chemotherapy requiring medical intervention and eight women suffered chronic toxicities requiring hospitalization and/or surgery. CONCLUSION: The neoadjuvant chemotherapy utilized in this trial was generally ineffective in converting patients from inoperable to operable, had no apparent effect on survival, and was associated with significant toxicity.

Phase I studies of continuous-infusion paclitaxel given with standard aggressive radiation therapy for locally advanced solid tumors.

Currently available therapies are unsatisfactory for locally advanced solid tumors of the lung, head and neck, and brain. Laboratory data suggest that the addition of paclitaxel (Taxol; Bristol-Myers Squibb Oncology, Princeton, NJ), a microtubule-stabilizing drug, to radiation therapy may result in significant radiation sensitization, perhaps because paclitaxel induces cell cycle arrest at G2/M. Relatively low concentrations, 1 to 10 nmol/L, appear to be optimal for direct cytotoxicity and radiosensitization in vitro. Within this dose range, more prolonged exposure seems to result in higher response rates. We are conducting phase I trials designed to test continuous infusion (24 hours per day, 7 days per week) intravenous paclitaxel combined with standard curative-intent radiation therapy. To date, 22 patients are evaluable, and the maximum tolerated dose of paclitaxel has not been reached at up to 2.5 mg/m2/d. Observed toxicities include anemia, lymphopenia, mucositis, and cutaneous erythema/desquamation.

The effect of naproxen on fever in patients with advanced gynecologic malignancies.

The antipyretic action of naproxen has been reported as sufficiently selective for neoplasm-related fever such that the use of this agent has been recommended to distinguish neoplastic from infectious fever. The antipyretic effect of naproxen was evaluated in gynecologic oncology patients with advanced pelvic malignancies and fever without obvious source of infection (suspected neoplastic fever). Naproxen (250 mg orally every 8 hr) was given to 12 patients with (i) a daily temperature greater than 38.3 degrees C, (ii) fever for at least 3 days, (iii) no evidence of infection on physical exam, (iv) negative results of blood and urine cultures, and (v) a chest roentgenogram negative for pneumonia. Ten of the 12 patients initially received a minimum of 3 days of empiric antibiotic therapy without resolution of fever. Within 24 hr of starting naproxen therapy, 10 patients' (83%) fever responded: Eight patients (80%) had a complete lysis of fever and two had partial lysis (20%). Temperature response was accompanied by subjective improvement in patient malaise and fatigue. Naproxen therapy was continued for 5-7 days in these patients, and chemotherapy was administered to those patients scheduled to receive it. Two patients did not respond to naproxen therapy in 24 hr; thus, it was stopped and the fever workup was continued. Of these two patients, one was eventually diagnosed with bacteremia after multiple negative blood cultures and initially no response to antibiotics. Naproxen is clinically useful in the palliation of fever-related symptoms in gynecologic oncology patients with suspected neoplastic fever. Naproxen may also allow the limitation of extensive fever workups and prolonged empiric antibiotic therapy in these patients, and prevent delays in systemic therapy or supportive care.

Primary vaginal melanoma: improved survival with radical pelvic surgery.

Primary vaginal melanoma is an aggressive and rare gynecological malignancy with < 150 reported cases to date. Historically, patients with this disease have a poor prognosis for all types of treatment. In several studies containing small numbers of patients conservative therapy often has been recommended. Eight patients from our institute with this disease were divided into two groups according to therapy: Group A, radical (4); and Group B, conservative (4). The groups were compared for stage, age, surface area of the lesion, and quality of life. The 2-year survival in Group A (75%) was significantly better than that of group B (0%). There was also found to be an improved survival in patients who had lesions with a surface area < 10 cm2. Age and stage of disease did not affect prognosis. Quality of life was not reduced in the radical group. A review of all reported cases since 1949 (119) was then performed. These were divided into the same Group A, radical (50); and Group B, conservative (69). Again, a statistically significant improved outcome was found with the radically treated patients (48%) when compared to the conservatively treated patients (20%). Our findings suggest that radical surgery for patients with primary vaginal melanoma is recommended in patients with lesions < 10 cm2.

Primary lung choriocarcinoma masquerading as a metastatic gestational neoplasm.

Primary lung choriocarcinoma has rarely been reported. In females, previous pregnancies and other sources of trophoblastic tissue such as a nongestational gonadal choriocarcinoma must be excluded before the diagnosis can be made. Here we present a young female patient initially diagnosed as having a metastatic gestational neoplasm who was unresponsive to standard single and multiagent chemotherapy. A total abdominal hysterectomy and bilateral salpingo-oopherectomy failed to reveal the source of production of beta HCG. At the time of her thoracotomy and lobectomy, performed for a lung nodule, she was found to have a primary lung choriocarcinoma. The patient received no further chemotherapy and has remained disease free for more than 3 years. This is the first recorded case of a lung choriocarcinoma that has been successfully treated where the patient has remained free of disease for more than 1 year.