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Background: Ovarian cancer (OC) requires complex multidisciplinary care with wide variations in outcome. We sought to determine the impact of institutional and process of care factors on overall survival (OS) and delivery of guideline care nationally., Methods: This was a retrospective cohort study of primary OC diagnosed from 1998 to 2007 using the National Cancer Data Base (NCDB) capturing 80% of all U.S. cases. Patient- (demographics, comorbidities, stage/grade), process of care (adherence to guidelines) and institutional- (facility type, case volume) factors were evaluated. Primary outcomes were OS and delivery of guideline therapy. Multivariable logistic regression and Cox proportional hazards models were used for analysis., Results: We analyzed 96,802 consecutive cases. Five-year OS was 84%, 66.3%, 32% and 15.7% for stages I, II, III and IV, respectively. The annual mean facility case volumes varied by cancer center type (range: 5.7 to 26.7), with 25% of cases spread over 65% of centers--all treating fewer than 8 cases. Overall, 56% of cases received non-guideline care. Low facility case volume and higher comorbidity index independently predicted non-guideline care; high volume centers were less likely to deliver non-guideline care (OR: 0.44, 95% CI: 0.41-0.47). Delivery of non-guideline care (OR: 1.4, 95% CI: 1.36-1.44), and higher facility case volume (OR: 0.91, 95% CI: 0.86-0.96) were both independent predictors of OS., Conclusions: Delivery of guideline care and facility case volume are important drivers of overall survival. Most cancer centers treat very few women with OC. National efforts should focus on improved access to centers with expertise in OC and ensuring delivery of guideline care., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: The relationship between racial and socioeconomic status (SES) disparities and the quality of epithelial ovarian cancer care and survival outcome are unclear., Methods: A population-based analysis of National Cancer Data Base (NCDB) records for invasive primary epithelial ovarian cancer diagnosed in the period from 1998 to 2002 was done using data from patients classified as white or black. Adherence to National Comprehensive Cancer Network (NCCN) guideline care was defined by stage-appropriate surgical procedures and recommended chemotherapy. The main outcome measures were differences in adherence to NCCN guidelines and overall survival according to race and SES and were analyzed using binomial logistic regression and multilevel survival analysis., Results: A total of 47 160 patients (white = 43 995; black = 3165) were identified. Non-NCCN-guideline-adherent care was an independent predictor of inferior overall survival (hazard ratio [HR] = 1.43, 95% confidence interval [CI] = 1.38 to 1.47). Demographic characteristics independently associated with a higher likelihood of not receiving NCCN guideline-adherent care were black race (odds ratio [OR] = 1.36, 95% CI = 1.25 to 1.48), Medicare payer status (OR = 1.20, 95% CI = 1.12 to 1.28), and not insured payer status (OR = 1.33, 95% CI = 1.19 to 1.49). After controlling for disease and treatment-related variables, independent racial and SES predictors of survival were black race (HR = 1.29, 95% CI = 1.22 to 1.36), Medicaid payer status (HR = 1.29, 95% CI = 1.20 to 1.38), not insured payer status (HR = 1.32, 95% CI = 1.20 to 1.44), and median household income less than $35 000 (HR = 1.06, 95% CI = 1.02 to 1.11)., Conclusions: These data highlight statistically and clinically significant disparities in the quality of ovarian cancer care and overall survival, independent of NCCN guidelines, along racial and SES parameters. Increased efforts are needed to more precisely define the patient, provider, health-care system, and societal factors leading to these observed disparities and guide targeted interventions.

Ureteroarterial fistulas (UAF) are a rare but potentially life-threatening complication of intra-abdominal malignancy, typically occurring after vascular or pelvic surgery. Patients with a history of radical pelvic surgery, chronic indwelling ureteral stents, and prior pelvic radiation appear to be at increased risk. The predisposing risk factors suggest that gynecological oncologists are the likely specialty to face this problem and should be familiar with the clinical presentation and etiology of UAF. We present two such cases to illustrate these salient points of clinical diagnosis and management.

Objective: To describe and evaluate the technique and the clinical outcome of a new modality for the treatment of women with persistent or recurrent pelvic malignancies utilizing surgically (laparotomy or laparoscopic) guided high dose rate (HDR) catheters to complete high dose rate interstitial irradiation therapy (LG-HDRT)., Methods: Between 6/2000 and 6/2004, 14 women with histologic evidence of postradiation persistent (3 patients) or recurrent (11 patients) pelvic disease underwent LG-HDRT. Five patients (36%) received treatment for a 2nd, 3rd or 4th recurrence. Preoperative clinical and radiologic evaluation to exclude evidence of extrapelvic disease was routine. Initial intraoperative evaluation included intraabdominal inspection and or biopsy to determine the extent of disease. A two "team" approach was used to place the 100 cm Teflon after loading HDR catheters. Each catheter had its open ends closed with bone wax prior to placement. Using a 14 gauge intravenous catheter as a guide, each HDR catheter was individually placed transvaginally. The tumor bed (treatment volume) was marked circumferentially with clips to facilitate treatment planning. Dosimetry was typically completed on the day of surgery and HDR therapy was started within the initial 24 postoperative hours. The catheters were removed transvaginally, without anesthesia following completion of therapy., Results: Mean patient age was 63.1 years and weight was 138.2 lb. Squamous cell cancer of the vagina or cervix was the most common (64%) diagnosis. The mean time from initial diagnosis to LG-HDRT was 67.9 months. The procedure was completed laparoscopically in 71% of patients, with 4 patients requiring laparotomy (3 conversions from laparoscopy). The mean duration of surgery was 94.9 min and the mean hospital stay was 4.8 days. Only 2 patients (14%) were discharged prior to the completion of therapy. The mean number of catheters placed was 6.1 and the mean dose delivered was 20 Gy over a mean of 5 fractions. There were no major intraoperative complications. Postradiation complications were limited to DVT (1), bladder bleeding (1),

Objectives: Compare important aspects of initial endometrial cancer treatment in women with or without primary management by a gynecologic oncologist (GYO)., Methods: A retrospective pattern of care study was conducted using tumor registry data from a community-based health care system. Surgically treated endometrial cancer cases were reviewed with respect to histology, training of surgeon(s), procedures, TNM staging, and prescription of adjuvant radiation., Results: Two hundred and seven consecutive cases completed between January 1998 and December 2000 were analyzed. Overall surgical stage was 78.4% stage I, 6.9% stage II, and 14.7% stage III-IV. Gynecologic oncologists (GYOs) provided care in 101 (48.8%) and gynecologists (GYNs) in 104 cases (50.2%). General surgeons (GSs) assisted gynecologists in 36.5% of cases. GYOs (94.0%) completed TNM staging two times more frequently (P < 0.05) than GYNs (45.2%). The incidence of lymph node assessment by GYOs was 83.0% (average number of nodes, 19.5) and GYNs 26.0% (average number of nodes, 7.7). Advanced disease (stage III-IV) was more frequently (P < 0.05) managed by GYOs (23.0%) than GYNs (6.7%). Radiation (RT) was prescribed to 36 (17.4%) patients. When evaluating TI and TII tumors at risk for extrauterine spread (G2-G3 or myometrial invasion), GYOs completed surgical staging more frequently than GYNs (95.7% vs. 18.8%, P < 0.05). GYO patients received radiation (six patients: 8.6%) less frequently than GYN patients (8.6% vs. 21.7%). No patient managed by GYOs with T1 N0 disease received RT. Eighteen percent of patients managed by GYNs with T1 N0 or T1 NX received RT., Conclusions: Gynecologic oncologists are more likely to evaluate and manage those with advanced endometrial cancer. Women with endometrial cancer managed by GYOs are more likely to receive comprehensive TNM surgical staging. The employment of complete TNM staging by GYOs reduced the use of RT in those with T1 N0 or Nx disease by 100%. These results suggest that primary management by gynecologic oncologists results in an efficient use of health care resources and minimized the potential morbidity associated with adjuvant radiation.

Unlabelled: The physical properties of Poly(L-lactide/glycolide) indicate that the suture retains approximately 80% of its original strength at 3 months and 60% of its original strength at 6 months. This new long-term synthetic absorbable suture offers postoperative fascial strength for an extended period when compared to other available absorbables. Importantly, many women with gynecologic cancer will undergo radiation therapy during this interval. This report is intended to evaluate the effects of ionizing radiation on this suture., Methods: One lot (op strands) of size 1 PLG suture was used. Ten (10) strands were used for baseline study of out of package tensile strength. Eighty (80) strands were placed in a buffer solution (pH approximately 9.0) and incubated in an in vitro water bath approximately 48 h at 55 degrees C to simulate 4 weeks in vitro residence time. Following this in vitro hydrolysis 20 strands were tested. Sixty strands were placed beneath a piece of fresh full thickness porcine skin and subcutaneous tissue and exposed to 3, 30, and 70 Gy. All samples were evaluated for breaking strength and elongation-at-break using an Instron tensiometer., Results: Analysis of variance performed at the different exposure level revealed no significant effect on tensile properties (p>0.1)., Conclusion: The tensile properties of PLG suture are not adversely affected by ionizing radiation. This long-term absorbable suture is an alternative for fascial closure when extended periods of support are necessary in patients destined to receive therapeutic ionizing radiation.

Objective: The goal of this study was to determine the outcomes of stage IC endometrial carcinoma patients who are managed with and without adjuvant radiation therapy after comprehensive surgical staging., Methods: Patients with FIGO stage IC adenocarcinoma of the endometrium diagnosed from 1988 to 1999 were identified from tumor registry databases at four institutions. A retrospective chart review identified 220 women who underwent comprehensive surgical staging including a total hysterectomy, bilateral salpingo-oophorectomy, pelvic/paraaortic lymphadenectomy, and peritoneal cytology., Results: Of the 220 stage IC patients, 56 (25%) patients received adjuvant brachytherapy (BT), 19 (9%) received whole-pelvis radiation (WPRT), and 24 (11%) received both WPRT and BT. One hundred twenty-one patients (55%) did not receive adjuvant radiation. There were 6 recurrences (6%) in the radiated group and 14 (12%) in the observation group (P = 0.20). Seven of fourteen recurrences in the observation group were local, and all local recurrences were salvaged with radiation therapy. Two of seven distant recurrences in this group were also salvaged with surgery and chemotherapy. The overall salvage rate for the observation group was 64%. There was a statistical difference in 5-year disease-free survival between the radiated and observation groups (93% vs 75%, P = 0.013). However, the 5-year overall survival was similar in the two groups (92% vs 90%, P = 0.717)., Conclusion: Adjuvant radiation therapy improves disease-free survival in surgical stage IC patients; however, overall survival is not improved with adjuvant radiation therapy since the majority of local recurrences in conservatively managed patients can be salvaged with radiation therapy.

Objectives: To describe the relationship between health literacy, distress, and cervical cancer risk factors in women at high risk for developing cervical cancer., Design: Cross-sectional, prospective cohort design., Setting: Two university-based gynecological oncology colposcopy clinics and 3 Planned Parenthood community dinics., Patients/participants: One hundred-thirty English-speaking African-American women > or = 18 years referred for colposcopy following abnormal Pap testing., Main Outcome Measures: Avoidance and Intrusion subscales of the Impact of Events Scale (IES), Rapid Estimate of Adult Literacy in Medicine (REALM), and demographics., Results: Forty-five percent of women had a low level of health literacy (< 9th grade). Low health literacy was related to fewer risk factors (P < .01) and higher levels of distress on the Impact of Events avoidance subscale (P < .05) after controlling for covariates. Forty-three percent of women with low literacy had excessive levels of distress as compared to 25% in women with high literacy (P < .05)., Conclusions: A low level of health literacy is associated with increased levels of distress among women at high risk for developing cervical cancer. To the extent that distress serves as a barrier to treatment, culturally informed, effective interventions are needed.

Surgical staging has become the standard of care for the treatment of women with endometrial cancer. Recent scientific publications have confirmed the relative safety of this procedure when performed by subspecialty trained surgeons and have provided compelling evidence that the routine use of postoperative teletherapy is not cost effective, nor does it offer improved survival. New questions as to the safety and effectiveness of a laparoscopic staging approach have been answered in the affirmative. Although the extent of staging has not yet been defined, growing evidence suggests that preoperative studies and intraoperative clinical opinion cannot be consistently counted on to be predictive of postoperative histologic status. Therefore, all patients should be considered at risk and should undergo an operation in a clinical situation that offers the immediate availability of retroperitoneal staging or cytoreductive surgery if necessary.

A review of available direct and indirect scientific reports strongly suggests that subspecialty training increases the likelihood that the appropriate surgical procedure will be completed in women operated on for gynecologic cancer. It is likely that specialty care lessens the costs associated with diagnosis, treatment and surveillance, and frequently improves survival.

Normal endometrium, an estrogen-responsive tissue, expresses the estrogen receptor (ER) alpha gene. Loss of ER expression, the basis for which is currently unknown, is often seen in advanced stage, poor prognosis endometrial tumors. The ER gene undergoes de novo methylation with high frequency in a wide variety of human tumors, including ER-negative breast cancers. In this study, we used several bisulfite-based detection methods to assess whether loss of ER positivity in endometrial tumors is associated with aberrant methylation of the ER gene. Although extensive methylation of a 600-bp region at the 5' end of the gene was seen in two endometrial carcinoma cell lines, none of the 55 CpGs in this region was methylated in 25 of 26 ER-deficient endometrial carcinomas.

Objective: The aim of this study was to investigate the influence of three treatment strategies for adenocarcinoma of the endometrium on the utilization of adjuvant radiation therapy and the medical charges associated with each pattern of practice., Methods: Three clinical algorithms felt to represent practice patterns for patients with endometrial cancer were considered: (1) comprehensive surgical staging of all patients, with adjuvant pelvic radiation reserved for documented cases of extrauterine disease, (2) total abdominal hysterectomy with bilateral salpingo-oophorectomy (TAH/BSO) with lymph node dissection reserved for cases of myometrial invasion, followed by adjuvant radiation based on the presence of uterine risk factors, and (3) TAH/BSO followed by intraoperative pathologic assessment of the uterus and consultation with a "surgical" oncologist for comprehensive staging. Each algorithm was applied to a cohort of 190 surgically staged patients identified through a retrospective medical records review. The use of radiation in each algorithm was quantified and the associated financial impact was estimated using hospital charges., Results: Treatment algorithm 1 yielded the lowest charges per patient at $12,778.52. Treatment algorithms 2 and 3 had associated charges per patient of $15,997.02 and $17,343.44, respectively., Conclusion: Approaches to care that lead to cost-effective utilization of health care resources should be pursued., (Copyright 1999 Academic Press.)

Background: We conducted a pilot study to evaluate issues related to chemotherapy-induced toxicities by eliciting assessments of toxicity from women with advanced stage ovarian cancer and gynecologic oncologists., Patients and Methods: Fifteen ovarian cancer patients and ten gynecologic oncologists completed the survey exercises. All patients surveyed had received at least six courses of a cisplatin-containing chemotherapy regimen., Results: For both patients and physicians, there was good face validity to the utility exercise as assessments of health states with cisplatin were (1) consistently associated with less favorable assessments than the health state with no toxicity and (2) neurotoxicity was viewed less favorably than either ototoxicity or nephrotoxicity. While the 15 patients as a group viewed health states with toxicity more favorably than physicians (P < 0.05 for each toxicity), patient assessments varied, depending on individual experiences with cisplatin. Physician assessments of toxicity were most similar to those obtained from patients who had not experienced cisplatin toxicity and were less favorable than those elicited from patients who had experienced any toxicity., Conclusions: In deciding upon therapeutic strategies, women with advanced stage ovarian cancer and treating physicians markedly differ in their assessment of the impact of specific toxicities on quality of life., (Copyright 1998 Academic Press.)

Background: Arteriovenous malformations (AVMs) are an abnormal communication between arterial and venous structures. Pelvic AVMs have been infrequently described in the literature and represent an uncommon cause of a palpable pelvic mass., Case: A case of pelvic AVM with ureteral obstruction occurred. The location and radiologic appearance of the AVM suggested a complex adnexal mass. During exploration and resection of the mass, significant bleeding was encountered. The diagnosis of AVM was made only retrospectively, with histologic examination of the specimen., Conclusion: AVMs are an uncommon and unique cause of pelvic pathology. Preoperative diagnosis will alert the surgeon as to the technically difficult resection that may be encountered and to the massive bleeding that can be associated with their removal.

Objective: Our aim was to determine whether histopathological variables predict persistent high-grade squamous intraepithelial lesions (HGSIL) after large-loop excision of the transformation zone (LLETZ)., Materials and Methods: All patients with cervical intraepithelial neoplasia (CIN) grade 2 or 3 on a LLETZ specimen with at least one follow-up Papanicolaou (Pap) test were identified. Histopathological variables were evaluated for the potential to predict HGSIL on a follow-up Pap test. Variables examined included endocervical margin status, ectocervical margin status, endocervical curettage (ECC) result, presence or absence of endocervical glandular involvement, and presence or absence of koilocytosis., Results: Two hundred and nineteen cases were identified. A follow-up Pap test showed HGSIL in 16 patients (7.3%). Of the histopathological variables studied, only a positive ECC at the time of LLETZ conization predicted HGSIL on follow-up cytology (p =.0002). Endocervical margin status, ectocervical margin status, presence or absence of glandular involvement, and presence or absence of koilocytosis were not associated significantly with HGSIL at follow-up., Conclusion: Most histopathological factors from LLETZ conization do not predict reliably the presence of HGSIL at the time of follow-up Pap test. A positive ECC at the time of LLETZ, however, may predict those patients destined to have persistence or recurrence. These findings suggest that conservative follow-up is warranted after LLETZ conization.

Objective: The aim of this study was to evaluate the response to salvage treatment in recurrent ovarian cancer treated initially with paclitaxel-based chemotherapy., Methods: A retrospective review of patients with recurrent ovarian cancer treated with surgical debulking and paclitaxel-based chemotherapy was performed. All cases received second-line treatment with a response evaluated by clinical or surgical means. Data analysis was conducted using the SAS statistical package., Results: Fifty cases of advanced stage disease were available for review. Patients received paclitaxel and cisplatin or carboplatin with a 72.0% response rate. The median time to recurrence after primary treatment was 6 months. Second-line treatment included cisplatin or carboplatin (50%), Taxol (10%), or lutetium (22%), an intraperitoneal radiolabeled monoclonal antibody targeted to TAG-72. A 52.0% clinical response to salvage treatment was detected. With a median follow-up of 7 months, 68.0% of patients had experienced recurrence or progression of their disease. The median time to second recurrence was 5 months. Cases sensitive to initial paclitaxel-containing chemotherapy responded to any of the salvage treatments more frequently than chemotherapy-resistant tumors (88.5% versus 11.5%, P < 0.05)., Conclusions: Recurrent ovarian cancer patients initially treated with paclitaxel-based chemotherapy frequently responded to salvage treatment. However, the duration of response was brief, and hospitalization for treatment-related side-effects was common. Tumor response to initial paclitaxel/platinum treatment was predictive of future response to second-line agents. Current salvage therapies appear to provide little benefit in cases of tumors resistant to primary chemotherapy.

Objectives: A case of small-cell carcinoma of the cervix and severe hypokalemia is presented. The need for surveillance of paraneoplastic syndromes in these patients is emphasized., Methods: The patient's clinical course is presented. The available literature regarding small-cell carcinoma of the cervix and Cushing's syndrome is reviewed., Results: A 32-year-old woman had diagnosed small-cell carcinoma after simple hysterectomy. After radical parametrectomy, she developed liver metastases that did not respond to chemotherapy. Subsequently, she developed severe and unremitting hypokalemia, which was determined to be the initial manifestation of Cushing's syndrome secondary to ectopic adenocorticotropic hormone production. Typical clinical features of Cushing's syndrome were noted to arise during subsequent examinations., Conclusions: Though paraneoplastic syndromes associated with small-cell carcinoma of the cervix are rare, this case report describes one of these syndromes as an etiology for metabolic derangements.

Objective: Our purpose was to examine the relationship between HER-2/neu expression and human papillomavirus infection in cervical glandular neoplasia., Study Design: Cases of cervical adenocarcinoma in situ and invasive adenocarcinoma were selected for study. Human papillomavirus typing was performed by in situ hybridization. HER-2/neu was detected by in situ hybridization and immunohistochemistry. Fisher's exact test was used to assess for statistical significance., Results: Fifteen cases of adenocarcinoma in situ and invasive adenocarcinoma were analyzed. In situ hybridization detected HER-2/neu messenger ribonucleic acid in 8 cases, whereas immunohistochemistry detected protein in 5 cases. Overall, HER-2/neu activity was present in 10 cases (66.7%). HER-2/neu messenger ribonucleic acid was detected more commonly in lesions associated with human papillomavirus type 16 versus type 18 (85.7% vs 25.0%, p = 0.04)., Conclusion: HER-2/neu is frequently expressed in human papillomavirus-infected glandular lesions of the cervix. In situ hybridization may provide a more sensitive indicator of HER-2/neu activity over immunohistochemistry. Preferential expression of HER-2/neu messenger ribonucleic acid was detected in human papillomavirus type 16 versus type 18 lesions. Further study is warranted to examine relationships between human papillomavirus infection and HER-2/neu expression.

Objective: The purpose of this study was to investigate contemporary methods of evaluating and treating abnormal Pap smears, in terms of their potential for excessive treatment and financial impact on health care delivery systems., Methods: Clinical algorithms for the evaluation and treatment of abnormal Pap smears were constructed, taking into consideration different philosophies on the need for colposcopic biopsy, the role of cryotherapy, and LLETZ. The algorithms employed (1) colposcopy of all patients with cryotherapy of mild dysplasia and LLETZ of moderate to severe dysplasia; (2) colposcopy with observation of mild dysplasia, treatment of moderate dysplasia by cryotherapy, and severe dysplasia by LLETZ; (3) colposcopy of LGSIL Paps before treatment and immediate LLETZ of HGSIL; and (4) immediate LLETZ of LGSIL and HGSIL Paps. Each algorithm was theoretically applied to a cohort of colposcopy clinic patients based upon referral Pap smear, with excessive treatment and costs calculated. The cohort's repeat Pap smear, colposcopic biopsy, and candidacy for cryotherapy were included in the analysis. The decision to use repeat Pap smear in treatment planning, submit only diagnostic LLETZ pathology, and select immediate LLETZ candidates by HGSIL/severe dysplasia Pap smear was considered. Financial impact was calculated using nationwide fiftieth-percentile reimbursement costs for procedures and related pathology., Results: Colposcopy provided little opportunity for excessive treatment. In contrast, 49.3% of cases subjected to immediate LLETZ would theoretically not have required treatment, if initially evaluated by colposcopy. The use of the subset of HGSIL cases encompassing severe dysplasia only identified patients suitable for immediate LLETZ, with an excessive treatment rate of only 2.8%. Traditional colposcopy (algorithm 2) would have been least expensive at $718 per patient. Algorithms 1 and 3 were intermediate at $785 and $754 per patient, respectively. Immediate LLETZ of all abnormal Paps (algorithm 4) would have been most costly at $838 per patient., Conclusions: The abandonment of colposcopy and reliance on immediate LLETZ for evaluation and treatment of cervical lesions would have been expensive and had significant potential for excessive treatment. Traditional colposcopic evaluation, coupled with observation of mild dysplasia, appeared to be the most cost-effective means of treating cervical dysplasia and had a low potential for excessive treatment.

Patients with extensive lower extremity ulcerations initially thought to be vascular disease were subsequently proved to have pyoderma gangrenosum and malignant lymphoma. Both patients died of sepsis; one patient exhibited hypogammaglobulinemia involving immunoglobulins IgA, IgG, and IgE; in the second patient, a polyclonal excess involving IgA and IgE was present.

The effect of diltiazem on vasoconstrictor responses was investigated in the feline mesenteric vascular bed under conditions of controlled blood flow. Diltiazem inhibited vasoconstrictor responses to sympathetic nerve stimulation, tyramine and norepinephrine suggesting that responses to both nerve-released and exogenous norepinephrine are dependent in part on an extracellular source of calcium. The calcium entry antagonist inhibited vasoconstrictor responses to alpha 1 and to alpha 2 adrenoceptor agonists over a wide range of concentration. Diltiazem also inhibited mesenteric vasoconstrictor responses to angiotensin II, vasopressin, prostaglandin F2 alpha and KCl. The inhibitor effects of diltiazem on vasoconstrictor responses to nerve stimulation and the pressor agents were reversible, and all responses returned to control value 30 to 45 min after the infusion of the calcium entry antagonist. The present data suggest that the inhibitory effects of diltiazem on responses to sympathetic nerve stimulation are postjunctional in nature, as responses to nerve-released and exogenous norepinephrine and nonadrenergic pressor agents are reduced to a similar extent. The present results suggest that vasoconstrictor responses to neuronally released and exogenous norepinephrine, as well as agents which activate membrane receptors or depolarize vascular smooth muscle in the feline mesenteric vascular bed, are dependent in part on an extracellular source of calcium. The inhibitory effects of diltiazem on vasoconstrictor responses to sympathetic nerve stimulation and pressor hormones may be relevant to the antihypertensive actions of this calcium entry antagonist.