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J R Benfield

Publications and source records attributed to J R Benfield.

At least 73 records · Page 4Linked to original sources
PubMed1986

Endobronchial carcinogenesis in dogs.

A canine model of squamous cell lung cancer has been developed through studies with 110 dogs exposed by 11 focal endobronchial regimens to chemical carcinogens: benzo(a)pyrene, nitrosomethylurea, methylcholanthrene, and dimethylbenzanthracene. A combination of nitrosomethylurea and benzo(a)pyrene caused the first invasive cancer after 5.5 years. Toxic side-effects resulted from either nitrosomethylurea or high-dose dimethylbenzanthracene given by bronchial submucosal injection and from adjuvant immunosuppression with azathioprine and corticosteroids. Four regimens in 58 dogs caused 31 cancers, including five T1-2 N0 M0 cancers, 17 metastasizing carcinomas, and nine carcinomas of lesser stages. The following regimens caused cancers: sequential benzo(a)pyrene, nitrosomethylurea, and yttrium 91; benzo(a)pyrene and topical nitrosomethylurea; low-dose dimethylbenzanthracene; high-dose methylcholanthrene. The most suitable regimen to date has been 30 mg of methylcholanthrene given by submucosal injection every 2 to 3 weeks; this produced cancers at preselected sites within 2 years of first exposure in eight of 10 dogs. The neoplastic continuum has followed a predictable, reproducible sequence that regularly began with epithelial hyperplasia. Squamous metaplasia occurred in 6 to 18 weeks; it was followed by progressive squamous atypia. The interval until invasive cancer developed varied with the regimen employed; it was about 20 months with methylcholanthrene. Serial cytologic specimens, studied by image analysis, revealed progressive increase in mean total cellular deoxyribonucleic acid content from diploid in normal cells to greater than tetraploid in cancer cells (p less than 0.01). We have recently been successful with serial passage of four canine lung cancers from four to twelve transplant generations in nude mice. There is now a predictable large animal model of squamous cell lung carcinoma at preselected site(s) that closely resembles human lung cancer. The preneoplastic period is short enough to be fiscally defensible, but long enough to permit study of the biologic changes during endobronchial carcinogenesis.

Adenocarcinoma↗
PubMed1985

Cell-cycle-dependent expression of human melanoma membrane antigen analyzed by flow cytometry.

Knowledge of tumor antigenic expression is crucial to the design of therapeutic strategy. A murine monoclonal antibody (BE4) against a human melanoma membrane antigen, was used to study the in vitro expression of this antigen. By membrane immunofluorescence, BE4 reacted against 5 of 8 melanoma lines as compared to zero of 13 other cell populations. Using flow cytometry, the antigenic M14 CEM melanoma cells consisted of 40% to 60% of the total cell population. Dual-parameter measurements of DNA content and membrane antigen demonstrated that the nonantigenic cells were predominantly in G0/G1 phase, whereas the antigenic cells were distributed throughout the cell cycle. Within one passage, the sorted and recultured nonantigenic population demonstrated a similar proportion of antigenic cells as the unsorted original population. It was concluded that the expression of human melanoma antigen was cell-cycle-dependent. Understanding factors that turn off the expression of antigen in G0/G1 phase may lead to better immunotherapeutic strategies.

Antibodies, Monoclonal↗
PubMed1985

Bronchopulmonary Kulchitzky cell carcinomas. A new classification scheme for typical and atypical carcinoids.

Typical and atypical carcinoids constitute less than 5% of lung tumors. They and small cell undifferentiated lung cancers (SCLC) belong to the same family of apudomas arising from bronchopulmonary Kulchitzky cells. To reflect the overlap among these cancers, the authors suggest calling them Kulchitzky cell carcinomas (KCC); to indicate their spectrum of aggressiveness, the authors suggest calling typical carcinoids KCC-I, atypical carcinoids KCC-II, and small cell cancers KCC-III. One hundred fifty-six KCCs were reviewed: 115 were KCC-I and 41 were KCC-II. The ratio of women to men equals 2:1. At time of initial diagnosis, all patients with KCC-I, except one patient, were in Stage I. Among patients with KCC-II, 16 (39%) were in Stages II or III at time of presentation. The incidence of carcinoid syndrome was 1.9%. Treatment was lobectomy in 112 (72%) of patients, the remainder having lesser resections or pneumonectomy in approximately equal distribution. Our data cannot support the use of radical resection in the treatment of KCC because none of the patients died of local recurrence. The mean diameters of KCC-I and -II tumors were 1.5 and 2.8 cm, respectively. Increased mitotic activity and tumor necrosis were reliable criteria for diagnosing KCC-II. Electron microscopic examination did not help in differentiating KCC-I and KCC-II. Thorough sampling of the entire tumor was found to be mandatory for precise diagnosis and for differentiation from KCC-III (SCLC). Measurement of nuclear DNA was done using integrated optical density (IOD) by image analysis. The IODs of KCC-I, -II and -III were 1.36, 1.55 and 1.94, respectively. These significant differences (P less than 0.001) correlated with the aggressiveness of the cancers. Of patients with KCC-I, 1.7% succumbed to KCC; this included one patient reported to have died of KCC-III (SCLC). Of 41 patients with KCC-II, 11 (27%) died of KCC; this includes at least 3 deaths from KCC-III.

Adolescent↗
PubMed1984

Carcinogenesis in canine bistomal heterotopic tracheal grafts.

Successful canine lung cancer models have required repeated focal bronchial carcinogen exposure under general anesthesia. To simplify serial studies of the respiratory mucosa during carcinogenesis, bistomal autologous heterotopic tracheal pedicle grafts have been made. These grafts can readily be returned to the original orthotopic site, and this has been shown to be a method with which to study reversibility of mucosal changes. Polycyclic aromatic hydrocarbons were applied topically to the mucosa three times a week for 21 to 22 months in 21 grafts. Implants of Silastic polymer from which carcinogen was released in sustained-release fashion were then left in the grafts for 4 to 6 weeks. Serial cytological and histological examinations showed development of atypical squamous metaplasia in the graft mucosa. Mucosal papillomatosis was noted in 4 of 7 grafts surgically excised 17 to 18 months after completion of carcinogen exposure. The heterotopic bistomal tracheal graft provides a useful method for studying respiratory epithelial carcinogenesis without repeated general anesthesia.

Animals↗
PubMed1984

A family of epidermoid lung cancer models.

A method of sustained release implantation has been developed whereby Silastic cylinders, impregnated with benzo[alpha]pyrene (BP) or methylcholanthrene (MCA) each at 2% (low dose) and 10% (high dose) concentrations, were inserted into the bronchus intermedius of hamsters. High-dose BP and MCA, and low-dose MCA had first-order exponential release rates: the half-time of release was 40 days for high-dose BP, 30 days for high-dose MCA, and 165 days for low-dose MCA. Release rate of low-dose BP was a second-order function: half-time of release was 40 days. Atypical squamous metaplasia was noted by 4 weeks in more than 65% of hamsters after insertion of each high-dose carcinogen but in less than 30% with the low-dose carcinogens. Carcinoma in situ was noted approximately 8 weeks after high-dose BP and 19 weeks after low-dose BP. At about 15 to 17 weeks after a high-dose carcinogen, 64% of animals had invasive epidermoid cancer, whereas after a low-dose carcinogen, only 21% did. After 25 weeks of exposure to a high-dose carcinogen, more than 85% of hamsters had invasive epidermoid cancer; up to 52 weeks were required for invasive epidermoid cancer to develop in 30% after a low-dose carcinogen. Measured by image analysis, nuclear deoxyribonucleic acid content of cells with severe atypical squamous metaplasia was greater than tetraploid (mean +/- standard deviation [SD], 3.77 +/- 1.4), whereas cells with invasive epidermoid cancer were suprahexaploid (mean +/- SD, 6.48 +/- 3.6). These differences are significant (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1983

Quantitative DNA. Comparative studies of a cellular marker for bronchogenic carcinoma.

During the course of induction of bronchogenic carcinoma in a colony of standard-bred beagles, serial cytologic and biopsy material was obtained under direct bronchoscopy. Cytological changes followed the sequence from metaplasia to carcinoma, closely simulating those features observed in humans, but with subtle differences characterized as species variations. Quantitative DNA done by image analysis correlated directly with the severity of cytologic atypia and also corresponded well with data obtained from humans. Equivalent studies in human bronchogenic carcinoma have shown similar results and strongly suggest that graded hyperploidy accurately reflects atypia in the lung and qualifies as an interspecies tumor marker.

Animals↗
PubMed1983

A prospective analysis of nosocomial wound infection after mastectomy.

We evaluated the postoperative course of all patients who had mastectomies from 1978 through 1982 at City of Hope National Medical Center (Duarte, Calif). The overall clean mastectomy wound infection rate was 24/294 (8.2%). The incidence of mastectomy wound infection varied with the method of biopsy and was 3.2% after needle aspiration and 9.5% after open biopsy. Mastectomy immediately after open biopsy ("one step") had an infection rate of 5.3%, whereas mastectomy at a subsequent procedure ("two step") had a rate of 12.4%. The maximal infection rate (23.0%) occurred following the two-step procedure when the interval was four to seven days. The infection rates for patients hospitalized three or more days before mastectomy were elevated, but no significant correlation was observed between the infection rate and other demographic factors. We recommend that needle aspiration biopsy be used prior to open biopsy to minimize the need for a two-step approach to mastectomy.

Adult↗
PubMed1983

Quantitative DNA determination by image analysis. II. Application to human and canine pulmonary cytology.

Comparative DNA measurements in human and canine preneoplastic and neoplastic tracheobronchial cells were made with the application of computerized image analysis. Canine studies demonstrated that the sequence of cellular events that precede epidermoid lung cancer simulates precisely the progression observed in humans. DNA studies concomitantly confirmed that there is a stepwise increase in DNA content with advancing nuclear atypia in metaplastic respiratory cells in both species. All carcinomas, regardless of histologic type, were significantly hyperploid to aneuploid (4c to 6c). Small-cell carcinoma exhibited a narrow modal distribution in the 4c region. The uniformity of the cytologic and quantitative DNA changes among these disparate species tends to confirm that humans and canines share biologic characteristics in bronchogenic carcinogenesis. The quantitative DNA measurements provide an objective cellular marker and may be used clinically for diagnostic purposes.

Adenocarcinoma↗
PubMed1983

Typical and atypical carcinoids within the pulmonary APUD tumor spectrum.

The behavior of pulmonary APUD tumors is not constant; management is controversial, and morphology has reached its limit as a tool for prognostic assessment and therapeutic planning. We have studied 24 patients with carcinoids; 17 patients with typical carcinoids presented with Stage I disease, but one patient later died most probably of small cell undifferentiated lung cancer (SCLC). Seven patients with atypical carcinoids included three with Stage III cancers, one patient with simultaneous bilateral carcinoids, and one patient with simultaneous adenocarcinoma. Of 17 patients with typical carcinoids, 16 or 92% are disease free or died of unrelated causes. Of seven patients with atypical carcinoids, five or 71% are disease free. Tumor doubling time of atypical carcinoids, was 79.6 months (45 to 120) or six times shorter than that of typical carcinoids (p less than 0.05). Two of the three deaths from cancer were probably from SCLC and one from a synchronous adenocarcinoma. Review of diagnostic material from 12 patients with SCLC who survived a mean of 41 months (24 to 134) showed that diagnosis had rested on cytology alone in four patients and that, in seven patients, the quality or extent of the original diagnostic material was adequate to make the diagnosis of a malignant tumor but inadequate to permit reclassification. Tumor cells from 11 patients with carcinoids (seven typical and four atypical) and 28 patients with SCLC had DNA measurement by image analysis. The mean DNA content of typical and atypical carcinoids and SCLC is 1.17, 1.25, and 1.94 respectively (p less than 0.001). These findings strongly suggest a relationship between DNA content and atypia or malignancy in APUD lung tumors. We conclude that there are at least two levels of virulence among carcinoids represented by typical and atypical carcinoids. The prognosis for treated Stage I typical and atypical carcinoids is excellent. When deaths occur, they are from systemic cancer. Current evidence indicates that DNA measurements by image analysis may help to discriminate levels of malignancy among APUD pulmonary cancers and thereby help to clarify therapeutic controversies.

Adenocarcinoma↗
PubMed1983

Intraoperative cytodiagnosis of lung tumors by needle aspiration.

Rapid-stain cytologic evaluation of needle aspirates are a recent adjunct to diagnosis and staging of lung neoplasms. The benefits of this approach include ease of sampling from deep and remote lesions and the fact that the results are generally available within 10 minutes. In the past 2 years, we did 187 needle aspirations for cytopathological evaluation in 70 patients at 51 thoracotomies and 21 mediastinoscopies. The cytologic findings from aspirates of lymph nodes, mediastinal masses, and intrapulmonary lesions were compared with diagnosis obtained by histopathological techniques. Quick-stain cytopathological evaluation discriminated cancer among all 55 lung masses from which aspirates were taken; specific diagnosis as to the type of neoplasm, lymphoproliferative disorder, or infection was achieved in 60 of 70 patients (85%). We conclude that intraoperative needle aspirations for cytologic evaluation facilitates the practice of modern general thoracic surgery.

Adult↗
PubMed1982

When and how to invade for the diagnosis and staging of primary lung cancer.

In search of perspectives pertaining to the selection of invasive procedures for evaluating patients with lung cancer, data from other centers were considered, and our recent consecutive experience with 40 lung cancer patients was reviewed. Cost estimates for the least and the most complete use of invasive procedures were done. An average of three procedures per patient was used. Information judged beneficial was obtained from 94 for 120 procedures (78 percent). By retrospective analysis, 15 procedures (0.38 per patient) provided no useful information. An approach to the use of invasive procedures in the management of patients with suspected lung cancer is proposed.

Adult↗
PubMed1982

Modern management of anastomotic leak after esophagogastrectomy.

From 1970 to 1981, 167 patients, aged 35 to 84 years (mean 61), underwent resection of 94 adenocarcinomas and 73 squamous cell cancers. The operative mortality was 8.9 percent. Anastomotic leaks occurred in 19 patients (11.3 percent), including 18 of 72 (25 percent) after operations for palliation and 1 of 95 (1 percent) after procedures with curative potential (p less than 0.01). The leakage rate after esophagogastrostomy was 8.5 percent, compared with 43 percent after interposition operations. No leak is attributed to cancer in anastomotic margins. In contrast to previous reports of greater than 50 percent mortality from leaks, only 21 percent of our patients died in the past decade. Four of 19 contained leaks (sinus tract or upper gastrointestinal) were treated nonoperatively; esophagostomy was used only once. Factors responsible for improving results include early diagnosis with routine contrast studies on the fifth to seventh postoperative days, mandatory use of total parenteral nutrition, nonoperative management of contained leaks, accurate, aggressive use of adjuvant chest tubes, and selective esophagostomy for anastomotic disruption.

Adenocarcinoma↗
PubMed1982

Lung cancer in young persons.

Lung cancer in patients under 40 years old is rare. Among 718 patients with lung cancer, 5% or 35 patients were younger than 40. All but one were heavy smokers. Twelve young patients who had operations survived 41.7 (SD 46.3) months: they included six who had resections of Stage 3 disease and who survived 19.2 (SD 16.0) months. The other six young patients treated operatively were free of nodal metastasis N0); all survived more than 3 years and three of them are apparently cured. The 23 young patients who were not treated operatively survived for 5.6 (SD 3.1) months. The 5 year survival rate of these young operated patients was not different from that of 201 operated patients over 40 years of age. Young nonoperated patients survived for a significantly shorter time (p less than 0.0001) than did the older patients who also received only chemotherapy and/or radiation as a treatment. In young patients adenocarcinomas predominated (48.6%), and the incidence of small cell undifferentiated cancers was high (28.6%). These significant differences as compared to the control group did not explain the short survival time of the young patients treated nonsurgically. We conclude that lung cancer in young persons is virulent and that diagnosis is frequently delayed. Therapy, in selected patients, should include aggressive resection, sometimes despite advanced local disease. This group of patients justifies innovative, intensive efforts at more prompt diagnosis and experimental multimodal therapy.

Adenocarcinoma↗
PubMed1982

Splenectomy for the treatment of hairy-cell leukemia.

In conclusion, patients with hairy-cell leukemia may need no therapy for prolonged periods. If they are symptomatic from hypersplenism, they may be expected to benefit from splenectomy. Some patients will have a relapse after splenectomy. At this time, there is no method to predict which patients will have a long term benefit from splenectomy, and we believe that operation should not be recommended as the primary therapy for hairy-cell leukemia.

Adult↗