Biomedical subjects

E V Hannigan

Publications and source records attributed to E V Hannigan.

At least 19 recordsLinked to original sources

PubMed2001

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.

Adult↗

PubMed2001

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.

Administration, Oral↗

PubMed2001

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.

Adult↗

PubMed2001

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.

Journal Article↗

PubMed1999

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.

Adenocarcinoma↗

PubMed1999

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.

Adenocarcinoma↗

PubMed1999

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.

Adult↗

PubMed1998

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.

Adult↗

PubMed1997

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.

Adult↗

PubMed1997

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.

Adenocarcinoma↗

PubMed1997

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.

Adenocarcinoma↗

PubMed1996

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.

Adult↗

PubMed1996

Intraperitoneal mitoxantrone or floxuridine: effects on time-to-failure and survival in patients with minimal residual ovarian cancer after second-look laparotomy--a randomized phase II study by theSouthwest Oncology Group.

A randomized phase II study of intraperitoneal (ip) mitoxantrone or floxuridine (FUDR) was performed for the treatment of minimal residual epithelial ovarian cancer found at second-look laparotomy after initial platinum-based chemotherapy. Entry was to take place within 30 days of reassessment laparotomies, with documentation of peritoneal metastases either microscopic or gross with cytoreduction to less than or equal to 1 cm in largest diameter. Patients were stratified by the site of the largest disease present (microscopic to 0.5 cm maximum diameter versus greater than 0.5 to 1 cm maximum diameter), by time of registration (< 14 days versus up to 30), and by serum CA-125 (< or = 35 versus >35 units/ml) prior to randomization to either ip mitoxantrone 10 mg/m2 every 2 weeks X 9 or ip floxuridine (FUDR) 3 g (total dose)/ day X 3 days every 3 weeks X 6 cycles. Implantable ip systems and 1.5-2 liters of normal saline were used to deliver the drugs of 83 patients registered between December 1988 and January 1994; there were 6 pathology exclusions and 9 surgical exclusions, and 1 nonevaluable patient for a total of 39 evaluable on mitoxantrone and 28 on FUDR being evaluable. FUDR is the choice for further study because of a progression-free survival exceeding 15% at 1 year over mitoxantrone and a median overall survival of 38 months. It should be emphasized again that the goal of a randomized phase II selection design is to select a winner for phase III testing should there be a substantial difference between the treatments with respect to the primary endpoint. Comparative conclusions between the treatment arms should not be attempted due to the inherently much smaller sample sizes. This should reemphasize the limitations in a comparison of efficacy; however, the toxicologic differences still emerge quite clearly.

Adult↗

PubMed1996

Treatment of human papillomavirus-associated vulvar disease with the CO2-laser. Physical and histological aspects with use of a new scanning device, the SwiftLase.

The CO2-laser has a successful record in treatment of extensive, refractory vulvar condylomas and vulvar intraepithelial neoplasia. A prerequisite for optimal use of the laser is careful preoperative diagnosis and optimized surgical technique based upon the exact knowledge of the interaction process between laser radiation and tissue. Using a new CO2-laser scanning device, the Sharplan Swift-Lase, this in-vivo study analyses the effects of CO2-laser parameters [average power density (PD), beam size and exposure time] on vulvar skin to determine optimum laser settings. Our histomorphometric analyses reveal a minimal skin destruction (ablation depth 40 microns, extent of irreversible thermal damage 80 microns to 120 microns) after application of the CO2-laser energy with the SwiftLase using a PD of 1000 W/cm2 with a beam size of 1 mm diameter. Previous CO2-laser application techniques required low PD (200 W/cm2 to 750 W/cm2) and a larger beam size (1.5 mm to 2 mm) moving over the epithelial surface as fast as possible to obtain a precise skin destruction. The SwiftLase allows the laser beam to be moved slowly with a beam size of 1 mm and significantly higher PD (up to 5000 W/cm2). These advantageous application conditions guarantee precise, homogeneous vulvar skin treatments with minimal thermal damage to the surrounding normal skin. The SwiftLase enables a less experienced colposcopists to perform vulvar CO2-laser surgery.

Carcinoma in Situ↗

PubMed1996

Bone metastasis in epithelial ovarian carcinoma.

Two cases of bone metastasis in patients with epithelial ovarian carcinoma and a review of the literature are presented. Bone metastases detected antemortem are rare and herald a poor prognosis.

Aged↗

PubMed1996

Tumor angiogenesis as a predictor of recurrence in stage Ib squamous cell carcinoma of the cervix.

OBJECTIVE: To explore the possibility of using histologic microvessel count of sections from the tumor to predict recurrence of stage Ib squamous cell carcinoma of the cervix. METHODS: Tumor sections from 22 patients (11 patients free of disease after 3 years and 11 patients with recurrence) were stained histoimmunochemically for factor VIII-related antigens. Vessel counting in the most active area of angiogenesis was performed by two pathologists on a x 200 microscopic field (0.739 mm2) without knowledge of the patient's' outcome. To predict recurrence, vessel count was compared with age, tumor size, tumor grade, lymph-vascular invasion, duration of follow-up, and type of therapy. RESULTS: Only high microvessel count (mean 19.9, range 7-43, versus mean 30.1, range 17-78; P < .05) and tumor size (mean 2.84 cm, range 1-4.2, versus mean 4.11 cm, range 2.2-6; P < .05) were independent factors predicting recurrence. CONCLUSION: High microvessel count in tumors may be used to predict recurrence in stage Ib squamous cell carcinoma of the cervix.

Adult↗

PubMed1996

Avoiding conization for inadequate colposcopy. Suggestions for conservative therapy.

OBJECTIVE: To determine if conservative treatment can safely be offered to patients with cervical intraepithelial neoplasia (CIN) and inadequate colposcopic examination. STUDY DESIGN: We reviewed the charts of 733 evaluable cone biopsies of the cervix performed for CIN at the University of Texas Medical Branch at Galveston from January 1981 to September 1990. RESULTS: Of 371 conizations that indicated inadequate colposcopy, there were 62 cases that fulfilled all the following conditions: cytologic smear suggesting CIN 2 or less, negative endocervical curettage (ECC) and cervical colposcopic biopsy showing CIN 2 or less. Pathologic examination of the cone biopsy specimen in these 62 cases revealed no dysplasia in 29.0%, CIN 1 in 16.%, CIN 2 in 37.0%, 3 in 17.7%, and no microinvasive or invasive lesions. Pathologic examination of the cone specimens of 309 patients with any high-risk factor--smear suggesting CIN 3 or invasive disease, colposcopic biopsy showing CIN 3 or positive ECC--revealed no dysplasia in 11.9%, CIN 1 in 11.3%, CIN 2 in 16.8%, CIN 3 in 49.8%, microinvasive carcinoma in 5.5% and frankly invasive carcinoma in 4.5%. CONCLUSION: Conservative therapy may be offered to patients with inadequate colposcopy, CIN 1-2 on both biopsy and cytology, and negative ECC without over-looking either invasive or microinvasive carcinoma. With these criteria, 16.7% of patients with an inadequate colposcopy in our study could have avoided cone biopsy.

Cervix Uteri↗

PubMed1996

Outpatient loop electrosurgical excision procedure for cervical intraepithelial neoplasia. Can it replace cold knife conization?

OBJECTIVE: To determine if loop electrosurgical excision procedure (LEEP) can replace cold knife conization. STUDY DESIGN: In a population at high risk for invasive carcinoma, 163 cases of LEEP conization were performed with the same indications as cold knife for cervical conization. RESULTS: Seventy-five percent of LEEP surgical specimens were positive for dysplasia. Six cases showed invasive squamous cell carcinoma. No complications were seen. CONCLUSION: LEEP conization is a quick, simple and economical procedure that can safely replace most cases of cold knife conization.

Adult↗