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Biomedical subjects

J R Van Nagell

Publications and source records attributed to J R Van Nagell.

At least 19 recordsLinked to original sources

Continuing participation supports ultrasound screening for ovarian cancer.

The effect of ovarian cancer screening on survival is enabled by women who continue to actively participate in screening. In this report, factors that affect participation are examined. Participants included 13,963 Kentucky women who received 56,392 screens accounting for a 46,113 screening year experience. Background, health history and reasons for participating in transvaginal sonographic screening were collected via a self-reported questionnaire. Screening participants were characterized as > 50 years old, mostly married, well educated, medically insured, health conscious women, living in the vicinity of the screening centre or 51-150 miles away. Approximately 70% of the participants can be considered active in the study based upon a screening visit during the 1997-1998 2-year period. The probabilities of a return screen at 1, 2, 5 and 7.5 years were 77.8%, 72.0%, 58.7% and 50.6%, respectively. A total of 96% of return visits occurred within 2 years, with 33.7% having intervals of < 1 year. Perceived family history was not observed to affect continuation. However, abnormal findings were associated with a shortened participation. These high levels of continuation in ultrasound screening indicate that women take this disease seriously and demonstrate that this disease is of consequence to them.

Adult↗

A feasibility study of 252Cf neutron brachytherapy, cisplatin + 5-FU chemo-adjuvant and accelerated hyperfractionated radiotherapy for advanced cervical cancer.

PURPOSE: To evaluate the feasibility and toxicity of 252Cf neutron brachytherapy combined with hyperaccelerated chemoradiotherapy for Stage III and IV cervical cancers. METHODS AND MATERIALS: Eleven patients with advanced Stage IIIB-IVA cervical cancers were treated with 252Cf neutron brachytherapy in an up-front schedule followed by cisplatin (CDDP; 50 mg/m2) chemotherapy and hyperfractionated accelerated (1.2 Gy bid) radiotherapy given concurrently with intravenous infusion of 5-Fluorouracil (5-FU) (1000 mg/m2/day x 4 days) in weeks 1 and 4 with conventional radiation (weeks 2, 3, 5, and 6). Total dose at a paracervical point A isodose surface was 80-85 Gy-eq by external and intracavitary therapy and 60 Gy at the pelvic sidewalls. RESULTS: Patients tolerated the protocol well. There was 91% compliance with the chemotherapy and full compliance with the 252Cf brachytherapy and the external beam radiotherapy. There were no problems with acute chemo or radiation toxicity. One patient developed a rectovaginal fistula (Grade 3-4 RTOG criteria) but no other patients developed significant late cystitis, proctitis or enteritis. There was complete response (CR) observed in all cases. With mean follow-up to 26 months, local control has been achieved with 90% actuarial 3-year survival with no evidence of disease (NED). CONCLUSION: 252Cf neutrons can be combined with cisplatin and 5-FU infusion chemotherapy plus hyperaccelerated chemoradiotherapy without unusual side effects or toxicity and with a high local response and tumor control rate. Further study of 252Cf neutron-chemoradiotherapy for advanced and bulky cervical cancer are indicated. We found chemotherapy was more effective with the improved local tumor control.

Adult↗

Clinical evaluation of 252Cf neutron intracavitary therapy for primary endometrial adenocarcinoma.

BACKGROUND: A pilot feasibility study of the neutron-emitting radioisotope 252Cf was done on patients with uterine adenocarcinoma and medically inoperable disease or unfavorable G3 histologic findings. METHODS: 252Cf intracavitary therapy was combined with 40-45 Gy of fractionated whole-pelvis photon therapy. In select patients, hysterectomy was performed. RESULTS: Thirty-one patients with Stage I-III adenocarcinoma of the corpus uteri were treated with 252Cf neutron brachytherapy. The patients treated often were in poor general medical condition and had multiple chronic medical illnesses for which conventional radiation and surgery usually would not be recommended. 252Cf allowed short implant treatment time (hours), was usable in a small number of insertions (the average number of insertions was two), and was useful for treating large volume tumors. Stage and grade of the tumor were important determinants of patient survival. The 5-year actuarial survival was 83% for patients with Stage I disease but only 37% for those with Stage II disease (primarily adenosquamous cell carcinomas). The 5-year survival was 100% for patients with Grade 1 tumors, 88% for those with Grade 2 tumors, and 21% for those with Grade 3 tumors. CONCLUSION: 252Cf neutron brachytherapy was found to be an effective and well-tolerated therapy for endometrial carcinoma. The excellent therapeutic efficacy and good patient tolerance make it suitable for additional evaluation in future Phase II-III trials.

Adenocarcinoma↗

Ovarian cancer screening in asymptomatic postmenopausal women by transvaginal sonography.

From November 1987 to January 1991, 1300 postmenopausal women underwent screening with transvaginal sonography (TVS). Women eligible for screening were all asymptomatic with no known ovarian tumors. Ovarian volume was calculated using the prolate ellipsoid formula, and a value in excess of 8.0 cm3 was considered abnormal. Ovarian abnormalities were detected in 33 women (2.5%), and 27 underwent exploratory laparotomy. Ovarian tumors were noted in all 27 patients, including 2 primary carcinomas and 14 serous cystadenomas. The two women with ovarian carcinomas had normal results of pelvic examinations and normal serum CA-125 levels. Both women had Stage I disease, and are alive and well after conventional therapy. TVS was time efficient, easy to perform, and well-accepted by patients. Currently, there are more than 3000 patient years of follow-up in the screened population, and there have been no deaths due to ovarian cancer. A multi-institutional trial to determine the efficacy of TVS as a screening method for ovarian cancer is indicated.

Adenocarcinoma↗

Neurologic complications of cervical cancer. A review of 2261 cases.

The authors reviewed the records of 2261 patients with histologically proven cervical cancer. Among the 1042 patients with carcinoma in situ, four neurologic complications occurred (0.4%), including three strokes and one seizure. None of the neurologic complications were related to cervical cancer. Among the 1219 patients with International Federation of Gynecology and Obstetrics (FIGO) Stage I or greater disease, 99 neurologic complications occurred (8%). Metastatic neurologic complications were twice as common as nonmetastatic neurologic complications and included lumbosacral plexopathy (50 patients), peripheral nerve compressions (eight patients), spinal cord compressions (two patients), and brain metastases (six patients). Nonmetastatic neurologic complications were less frequent and included stroke (11 patients), encephalopathies (three patients), infectious complications (two patients), effects of therapy (six patients), and seizures (11 patients). In conclusion, neurologic complications are rare in cervical cancer and virtually nonexistent in Stage 0 disease. Metastatic neurologic complications were more common than nonmetastatic complications and lumbosacral plexopathy caused by retroperitoneal lymph node metastases was the most common neurologic complication.

Adolescent↗

Feasibility study of Californium-252 for the therapy of stage IV cervical cancer.

Twenty patients with Stage IVA and IVB cervic cancers were treated with Californium-252 (Cf) neutron brachytherapy (NT) in a feasibility trial between 1976 and 1986. Eleven patients had Stage IVA disease; nine patients had Stage IVB disease. Patient compliance with therapy was poor in four of nine patients with Stage IVB disease, and the 50% survival time was 6 months. In Stage IVA disease there were 18% 3-year survivals. For those that failed, the 50% survival time was 7.5 months. Because of the frequency of disseminated metastases, effective adjuvant therapy needs to be developed to use after the tumor debulking therapy, especially for Stage IVB disease. A single early Cf-NT implant followed by 6000 cGy of whole-pelvis fractionated radiation would accomplish this adequately for local tumor control and palliation.

Adult↗

The effects of acute administration of cytotoxic anticancer agents on the capacity for subsequent hormonal responses in the mouse uterus.

The mouse uterus has been used as a model system with which to examine the interaction of anticancer agents with steroid hormone receptors and to evaluate the effect of a single exposure to a cytotoxic anticancer agent on the subsequent elicitation of the uterotrophic response to estradiol. The uterotrophic response was interpreted in terms of the induction of progesterone receptors, uterine weight gain and increased uterine DNA content. Evaluation of 34 cytotoxic agents selected for this study provided little evidence to substantiate the interaction of these agents with estrogen or progesterone receptors. Although prior treatment with certain cytotoxic agents partially inhibited the subsequent responses to estradiol, some capacity to respond to estradiol was always retained. The majority of cytotoxic agents had little impact on the capacity to respond to estradiol. Thus, in these studies where high sublethal concentrations of cytotoxic agents were administered prior to estradiol, there was no indication that the mechanisms regulating subsequent hormonal responses were compromised.

Animals↗

Proliferation, esterase activity, and propidium iodide exclusion in urologic tumor cells after in vitro exposure to chemotherapeutic agents.

After exposing urological tumor cells to anticancer agents in vitro, cellular esterase activity and the ability to exclude propidium iodide (PI) were examined as dual indicators of functionality or "viability." High esterase activity/PI exclusion was observed in assays in which anticancer agents failed to inhibit cellular proliferation, while low esterase activity/PI exclusion was often observed when proliferation had been significantly inhibited. In a number of instances, exposure to anticancer agents did produce significant inhibition of proliferation without lowering viability. In this setting, the recovery of proliferative capacity could be demonstrated with several transitional cell carcinoma cell lines, and this recovery was always associated with high esterase activity/PI exclusion. When the proliferation of primary urological tumor preparations was inhibited by drug exposure, estimates of elevated viability were obtained in 27 per cent of the determinations. Thus, viability estimates may be an indicator of the potential for tumor-cell recovery from exposure to anticancer agents. Moreover, the potential for recovery may explain differences between the results of chemosensitivity testing and actual clinical events by reconciling clinical failures with elevated viabilities indicative of this potential.

Antineoplastic Agents↗

Clinical trial of 252Cf neutron brachytherapy vs. conventional radiotherapy for advanced cervical cancer.

252Cf, a neutron emitting radioactive transplutonium isotope, was tested for its efficacy against advanced bulky Stage III-IV cancers of the cervix in a clinical trial at the University of Kentucky Medical Center. Eighty-two patients were treated during 1976-1979 and followed for 5-year survival and tumor control. Three different treatment methods went on sequentially and concurrently, that is, (a) conventional whole pelvis photon with delayed 137Cs implants, (b) conventional photon therapy with delayed 252Cf implants, and (c) 252Cf implants ("early") preceding photon therapy. There were 12% 5-year survival for Stage IIIB cancers by conventional therapy, and 15% by delayed 252Cf implant therapy. For early 252Cf implant therapy there were 54% 5-year survivals with 4% complications and 65% 5-year local control, but distant metastases became a prominent delayed failure pattern.

Adult↗

The proliferation of human tumor cell lines in the presence of different agars, agaroses, and methyl cellulose.

Human tumor cell lines, derived from cancers of the colon, ovary, and cervix, were grown in liquid tissue culture media and media made semisolid with agar (Bacto + deoxycholate lactose agar), agarose [LE, ME, Sea Plaque and Sea Prep (15/45)], and methyl cellulose. The effects of each agent on overall cell proliferation and rate of overall cell proliferation were examined. The agents, used to make media semisolid, were observed to inhibit or, in some cases, enhance cell growth in a fashion that was characteristic of individual cell lines. These phenomena may be of consequence to the optimization of nutrient media for primary tumor cell preparations.

Agar↗

Role of bone scanning for evaluation of carcinoma of the cervix.

The value of X-ray studies and bone scan studies of cervix cancer patients was evaluated by a review of patient charts and bone scans or X-ray studies. No in situ cancer patients had positive studies. A low frequency of positive X-ray studies was observed ranging from 1% with stage I to 10% with stage IV disease. Recurrent carcinoma had 10% positive studies. Bone scans correlated well with positive X-ray studies but 10% false-positive scans were seen, mostly osteoarthritis. The bone scan was much more sensitive and appeared to detect an earlier stage lesion, usually associated with symptoms which with radiation and other treatments could follow a more indolent course than the patient with a positive X-ray study. The present study evaluates the appearance and value of these studies, the frequency and circumstances under which useful information was obtained, and what type of survival followed the establishment of the diagnosis.

Adenocarcinoma↗

Tumor regression and histologic clearance after neutron brachytherapy for bulky localized cervical carcinoma.

The response of bulky, advanced Stage 1B and early Stage II carcinoma of the cervix to neutron brachytherapy (NT and radiotherapy) was studied using combined NT radiation and extrafascial hysterectomy with histologic evaluation. Scheduling of neutron therapy relative to external beam photon therapy, tumor volume, tumor stage, tumor histology, and clinical tumor clearance were assessed in these studied. NT was easily combined with surgery in this study. Low stage tumors, small tumor volume and "early" neutron implants (scheduled within +/- one week of the start of fractionated radiation) showed more frequent histologic clearance of tumor. Long-term tumor control has been achieved and failures developed distance metastases without pelvic or local recurrence. This experience indicates that NT was effective for tumor clearance and control and represents and promising new modality for localized, advanced tumor therapy.

Adult↗

Californium-252 neutron curietherapy for advanced cervical cancer.

Low dose rate neutron radiotherapy using fast neutrons emitted by the radionuclide 252Cf was combined with fractionated X- or gamma rays for the radiotherapy of advanced cervicovaginal tumors. Two different implant schedules were tested to determine the response of the tumors to the scheduling of therapy with the 252CF either early or delayed in the fractionated radiotherapy course. A 90% frequency of complete local clearance of pelvic tumors was observed by the early application of 252Cf. Neutron curietherapy applied as a boost treatment at the end of fractionated radiotherapy, resulted in only 40% local control. Improved results were observed by early implantation therapy and is postulated to be the result of more effective hypoxic tumor therapy and reoxygenation of the hypoxic pelvic tumor. The two groups of patients were compared as to their general status and medical condition and were found similar in age, frequency of associated disease, body weight and tumor stage. The failures of local control by early 252Cf neutron therapy, occurred in 2 patients with high-stage tumor and severe vascular disease and suggests that tumor response was partly dependent upon the integrity and elasticity of the small vessel system.

Adult↗

Experience with an alternative method of anesthesia for intracavitary therapy of pelvic carcinoma.

Placement of intracavitary applicators for treatment of gynecological cancer is usually done in the operating room under general anesthesia. This requires premedication, operating and recovery room time, and is time consuming and expensive. The authors have found that the implant can be performed in a radiation medicine department using intravenous Demerol and Valium. Analgesia has many advantages in comparison to general anesthesia for intracavitary implant therapy.

Analgesia↗

Californium Cf-252 for pelvic radiotherapy.

Clinical data about therapy concerning tumors of the female gynecological cancers of the cervix, vagina and uterus are reviewed. Dosimetric, laboratory and radiobiological research data form the basis for an approach to such tumors using Cf-252 as a form of boost brachytherapy. Extreme personnel hazards are a real and important consideration and indicate that maximal containment and isolation procedures should be exercised in its use. But it is anticipated that new possibilities for successful radiotherapy of an important cagegory of tumor will be realised by its clinical evaluation and application.

Californium↗

Small cell cancer of the uterine cervix.

Forty-one patients with small cell carcinoma of the uterine cervix were evaluated and treated at the University of Kentucky Medical Center from 1962 to 1974. Eighteen patients (44%) developed widespread metastases and died of recurrent cancer within 2 years of therapy. Common sites of metastases included the lung, liver, and bone. There was a significantly lower incidence of lymphoplasmacytic infiltration in small cell cancers than the keratinizing or nonkeratinizing squanmous cell carcinomas of the cervix. In addition, there was a significant increase in the number of unstimulated regional lymph nodes in patients with small cell cancer when compared with the lymph nodes of patients with the other cell types of cervical cancer. These data suggest that small cell cancer of the cervix is a highly aggressive tumor similar to small cell carcinoma of the lung and behaves quite differently from other types of squamous cell carcinoma of the cervix. Radiation therapy was superior to radical surgery in eradicating pelvic disease, but prospective studies need to be undertaken to determine the effect of adjunctive chemotherapy in patients with this rare tumor.

Adult↗