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J C Nesbitt

Publications and source records attributed to J C Nesbitt.

33 records · Page 2Linked to original sources
PubMed1995

Retinoid refractoriness occurs during lung carcinogenesis despite functional retinoid receptors.

Retinoids have demonstrated activity in the prevention of second primary tumors in patients with non-small cell lung cancer (NSCLC). They also contribute to the normal growth and differentiation of human bronchial epithelial (HBE) cells. Because retinoids mediate their actions through retinoid nuclear receptors (RARs and RXRs), aberrant signaling through retinoid receptors could contribute to lung carcinogenesis. Using a lung carcinogenesis model consisting of normal, premalignant, and malignant HBE cells, we examined all-trans retinoic acid (t-RA)-induced changes in cellular growth. These studies revealed that t-RA treatment inhibited the growth of normal HBE cells, but premalignant and malignant HBE cells were relatively resistant to t-RA. Coincident with the development of retinoid refractoriness, basal expression of the retinoic acid nuclear receptor beta (RAR-beta) increased. Analysis of receptor function by gel shift and transient transfection assays of normal, premalignant, and malignant HBE cells demonstrated that receptor-DNA binding and transcriptional activation properties were intact in the t-RA-refractory malignant HBE cells. To compare these findings to NSCLCs in patients, we investigated retinoid receptor expression in NSCLC biopsies. A subset of the tumors expressed RAR-beta, reflecting the RAR-beta expression observed in the malignant HBE cells in culture. These findings demonstrate that retinoid receptor function was intact in the t-RA-refractory malignant HBE cell line, suggesting that the defect in retinoid signaling in this lung carcinogenesis model is not intrinsic to the retinoid receptors.

Animals↗
PubMed1995

Malignant pleural mesothelioma after radiation therapy for breast cancer. A report of two additional patients.

BACKGROUND: Malignant pleural mesotheliomas (MPMs) are rare tumors that usually have a fatal outcome. The association of these tumors with asbestos exposure is well established. Induction of malignant mesothelioma by nonasbestos-related causes also has been reported in the literature, although the number of documented cases is extremely small. Two additional patients with malignant pleural mesothelioma many years after radiotherapy for breast cancer are reported. METHODS: The observations as reported in the literature on the involvement of radiation in the development of MPMs are reviewed and compared with the authors' clinical experience. In a retrospective random review, 1000 patients who received thoracic irradiation at M. D. Anderson Cancer Center were studied for histologic and radiographic evidence of MPM. The selection criteria included the development of a unilateral pleural effusion years after successful treatment with thoracic irradiation for a proven malignancy. Patients with a history compatible with asbestos exposure were excluded from the review. RESULTS: There have been only three previous cases of documented MPM associated with thoracic irradiation reported in the English literature. A review of the experience at our institution has demonstrated three patients with radiation-induced MPM. One patient has been reported elsewhere. Details of the other two patients are discussed in this paper. CONCLUSIONS: Nonasbestos-related causes of MPMs are rare. The additional two patients lend added support to the association between thoracic irradiation and the development of MPM. The development of a unilateral pleural effusion occurring years after successful treatment of a proven malignancy with thoracic irradiation should alert the clinician to the possibility of MPM.

Aged↗
PubMed1995

Tumor implants after thoracoscopic resection of a metastatic sarcoma.

Tumor implantation after video-assisted thoracic operations is rare. We describe the case of a 61-year-old woman who underwent an apparently uneventful thoracoscopic resection of a solitary pulmonary metastasis from a primary limb sarcoma. Within 3 months, extensive trocar and diaphragmatic implants developed that required an extensive en bloc resection of her chest wall, diaphragm, and lung. Because of the aggressive biologic behavior of sarcomas and their potential to grow in surgical tracts, concern is raised about the advisability of using video-assisted thoracic surgical techniques in the management of these tumors.

Female↗
PubMed1995

Survival in early-stage non-small cell lung cancer.

The duration of survival in early-stage lung cancer (stages I and II) varies between reports in the literature. Several reasons account for this: patient population heterogeneity, inconsistent staging, anatomic variability, dissimilar tumor morphology, and unpredictable tumor biology. This report addresses some of the issues in early-stage non-small cell lung cancer that relate to variability between estimates of survival in end stage reporting. We review several large series since the introduction of the International Staging System in 1986 and other selected, contemporary reports that address end results in patients with pathologic stage I or stage II lung cancer. Overall survival for patients with pathologic stage I disease is 64.6% (range, 55% to 72%) and 41.2% for patients with stage II disease (range, 29% to 51%). Reducing morphologic differences by placing patients in groups based on the TNM subset and refinement in categorization by matching TNM subsets based on histology and other factors can improve considerably homogeneity and enhance prognostic predictability. The development of more accurate measures for predicting prognosis may serve to clarify the roles of primary and adjuvant treatment, particularly in those patients with early-stage disease associated with poor prognostic factors in whom the potential for long-term survival is reduced.

Biomarkers, Tumor↗
PubMed1995

Resection of sternal tumors: extent, reconstruction, and survival.

BACKGROUND: Resection of sternal tumors may be tailored to the patient and the location of the malignancy. METHODS: We reviewed our results of sternectomy (typically 5-cm margins) performed in 30 patients over a 10-year period. RESULTS: Thirteen patients had primary sternal sarcoma (six chondrosarcoma, five osteosarcoma, two other); 10 patients had local recurrence from breast cancer; 4 patients had metastases; 3 patients had other (two osteoradionecrosis, one malignant fibrous histiocytoma). Morbidity occurred in 8 patients (26.7%): wound dehiscence, 2; wound infection, 1; hemorrhage, 1; pneumonia, 1; prolonged air leak, 1; empyema, 1; and bronchopleural fistula, 1. One patient, with multiple metastases, died from adult respiratory distress syndrome on day 25 (overall mortality, 3.3%; 1 of 30). The area of reconstruction ranged from 35 to 264 cm2. The technique of reconstruction included muscle flap alone in 13 patients; muscle flap and mesh, 9; muscle flap and rigid prosthesis (Marlex methylmethacrylate), 7; or other, 1 patient. Nineteen patients (63%) were extubated within 24 hours after operation. Median intensive care unit stay was 2 days; median hospitalization, 6 days. Late local recurrence after resection occurred in 6 patients; 4 from breast cancer (3 patients had concurrent distant metastases). Five-year actuarial survival after primary tumor resection was 73% and 33% after resection of recurrent breast cancer (median, 21 months). CONCLUSIONS: Partial sternectomy may be performed for primary sternal tumors with short hospitalization and good local control. Wider local excision or total sternectomy may minimize local re-recurrence of breast carcinoma to the sternum.

Actuarial Analysis↗
PubMed1995

Is follow-up of lung cancer patients after resection medically indicated and cost-effective?

BACKGROUND: There are no guidelines for the appropriate follow-up of patients after pulmonary resection for lung cancer. METHODS: Three-hundred fifty-eight consecutive patients who had undergone complete resections of non-small cell lung cancer between 1987 and 1991 were evaluated for tumor recurrence and development of second primary tumors. Recurrences were categorized by site (local or distant), mode of presentation (symptomatic or asymptomatic), treatment given (curative intent or palliative), and duration of overall survival. RESULTS: Recurrences developed in 135 patients (local only, 32; local and distant, 13; and distant only, 90). Of these, 102 were symptomatic and 33 were asymptomatic (most diagnosed by screening chest roentgenogram). Forty patients received treatment with curative intent (operation or radiation therapy > 50 Gy) and 95 were treated palliatively. The median survival duration from time of recurrence was 8.0 months for symptomatic patients and 16.6 months for asymptomatic patients (p = 0.008). Multivariate analysis shows that disease-free interval (greater than 12 months or less than or equal to 12 months) was the most important variable in predicting survival after recurrence and that mode of presentation, site of recurrence, initial stage, and histologic type did not significantly affect survival. New primary tumors developed in 35 patients. CONCLUSIONS: Although detection of asymptomatic recurrences gives a lead time bias of 8 to 10 months, mode of treatment and overall survival duration are not greatly affected by this earlier detection. Disease-free interval appears to be the most important determinant of survival. Screening for asymptomatic recurrences in patients who have had lung cancer is unlikely to be cost-effective. Frequent follow-up and extensive radiologic evaluation of patients after operation for lung cancer are probably unnecessary.

Adult↗
PubMed1994

Management of tracheal and bronchial stenoses with the Gianturco stent.

Thirty-six cancer patients with symptomatic tracheobronchial stenoses received Gianturco tracheobronchial stents over a 9-year period. Symptoms improved in 28 patients (78%). The overall median survival was 1 month 3 weeks (range, 4 days to 35 months). The median survival for patients who showed improvement after receiving stents was 3 months compared with 1 week for those who did not respond. Complications were minimal. The Gianturco stent may palliate symptoms of tracheobronchial compression in selected cancer patients.

Adult↗
PubMed1994

Resection of lung cancer is justified in high-risk patients selected by exercise oxygen consumption.

The medical criteria for inoperability have been difficult to define in patients with lung cancer. Sixty-six patients with non-small cell lung cancer and radiographically resectable lesions were evaluated prospectively in a clinical trial. The patients were considered by cardiac or pulmonary criteria to be high risk for pulmonary resection. If exercise testing revealed a peak oxygen uptake of 15 mL.kg-1.min-1 or greater, the patient was offered surgical treatment. Of the 20 procedures performed, nine were lobectomies, two were bilobectomies, and nine were wedge or segmental resections. All patients were extubated within 24 hours and discharged within 22 days after operation (median time to discharge, 8 days). There were no deaths, and complications occurred in 8 (40%) of the 20 patients. Five patients whose peak oxygen uptake was lower than 15 mL.kg-1.min-1 also underwent surgical intervention; there was one death. Thirty-four patients whose peak oxygen uptake was less than 15 mL.kg-1.min-1 and 7 who declined operation underwent radiation therapy alone (35 patients) or radiation therapy and chemotherapy (6 patients). There were no treatment-related deaths, and the morbidity rate was 12% (5/41). The median duration of survival was 48 +/- 4.3 months for the patients treated surgically and 17 +/- 2.7 months for those treated medically (p = 0.0014). We conclude that a subgroup of patients who would be considered to have inoperable disease by traditional medical criteria can be selected for operation on the basis of oxygen consumption exercise testing. There is a striking survival benefit to an aggressive surgical approach in these patients.

Adenocarcinoma↗
PubMed1994

Lung tumor resection does not affect debrisoquine metabolism.

Some authors have reported an association of extensive metabolism of debrisoquine with increased lung cancer risk, although others have found no association. Debrisoquine metabolism is controlled by a cytochrome P-450 isozyme encoded at the CYP2D6 locus, which is inducible by antipyrine and rifampicin. Because lung tumors may produce a variety of humoral substances, we wanted to determine whether the tumor induced debrisoquine metabolism. As part of a case-control study of lung cancer, debrisoquine metabolism was measured in patients with histologically confirmed non-small cell lung cancer before and after surgical resection with curative intent. One hundred four incident patients with curative intent. One hundred four incident patients with pathological stage I, II, or IIIA non-small cell lung cancer took debrisoquine (10 mg) orally at 10 p.m. and collected the subsequent 8-h urine both before and after surgery. We compared the values of the metabolic ratio, which is the percentage of the dose excreted as debrisoquine to the percentage of the dose excreted as the principal metabolite. The pre- and postoperative metabolic ratios were highly correlated (Pearson correlation coefficient = 0.96), and did not differ in value significantly (P = 0.88). Using traditional cutpoints (metabolic ratio, 1.0 and 12.6) to categorize the three metabolic phenotypes, the preoperative and postoperative phenotypes were well correlated (kappa = 0.78). These results show that the ability to metabolize debrisoquine is not induced by the presence of a primary lung tumor.

Carcinoma, Non-Small-Cell Lung↗
PubMed1987

Surgical management of esophageal perforation.

The recognition and management of esophageal perforation remain a problem. Diagnostic and treatment delays are common, and controversy continues regarding approaches to surgical intervention. Overall survival has increased with improved adjunctive modalities; however, morbidity and mortality remain high. A total of 115 consecutive cases of nonmalignant esophageal perforation were reviewed. There were 69 thoracic, 27 cervical, and 19 abdominal perforations. Etiology of the perforations was iatrogenic in 65 patients, traumatic in 28, and spontaneous perforation in 22. Symptoms included pain (71%), fever (51%), dyspnea (24%), and crepitus (22%). Contrast roentgenography was used in 78 patients and demonstrated the perforation in all but two patients. All but 20 patients had operations. In the last decade, the survival rate was 11.4 per cent for patients treated within 24 hours of perforation. Survival significantly improved in the last 10 years because of hyperalimentation, cardiopulmonary monitoring, and better antibiotic coverage. Treatment of choice is primary closure with drainage, regardless of the duration of the perforation. In selected patients who have cervical esophageal perforation, nonoperative management has a role.

Esophageal Diseases↗
PubMed1986

A new model to study acute and chronic renal failure.

Many models have been developed to study renal function following injury. Two types of studies have evolved: acute--to define the acute renal injury and chronic--to determine the pattern of recovery. Current models allow either study alone to be performed, but they lack the flexibility to combine the studies. In this study of renal ischemia, a model was designed which solved this problem. The authors constructed a model for performing a unilateral nephrectomy and episiotomy on female dogs. Catheters were placed in the renal vein, vena cava, and aorta, and a renal artery flow cuff was applied. The catheters and wires were buried in a subcutaneous pocket and were exteriorized after a recovery of several weeks. The episiotomy allowed easy intermittent Foley catheterization. With the animals awake and in a harness, parameters of renal function were measured: renal extraction, filtration fraction, fractional excretion, osmolar clearance, and free water clearance. Glomerular filtration rate and renal plasma flow were calculated by inulin and paramino hippurate clearances. The animals were studied in diuretic and antidiuretic states. In addition, renal artery flow was determined by the Doppler flow cuff. All parameters were determined every half hour in the acute setting, then every day in the chronic setting. The model was easily reproducible and functioned well in the authors' renal ischemia studies. Initial experiments with 1 hour of warm ischemia produced a greater than 50 per cent reduction in GFR acutely. Chronic studies showed a GFR with a return toward normal. All model construction purposes and plans were met.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Kidney Injury↗
PubMed1985

Colorectal carcinoma in pregnancy.

Colorectal carcinoma in pregnancy is rare. The symptoms frequently are masked by the symptoms associated with normal pregnancy, resulting in delayed diagnosis. Based on our experience with five patients and review of the literature, we developed a management regimen that takes an aggressive approach to tumor excision, yet maintains the pregnancy and fertility if possible. The prognosis is poor for most patients because the stage of the tumor is usually advanced at the time of diagnosis. The key to improved survival, as with all cancers, is early diagnosis and treatment.

Adult↗
PubMedDate not supplied

Cellular schwannoma of the bronchus.

A cellular schwannoma in a bronchus of a 64-year-old female is reported with immunocytochemical and ultrastructural observations. One previous case arising in the lung has been reported. The tumor formed a 3-cm exophytic mass in a segmental bronchus. Pneumonectomy was performed. The tumor was moderately cellular and devoid of Verocay bodies, and the spindle cells were immunoreactive for S-100 protein. Electron microscopy revealed schwannian features that were less developed than in a classic schwannoma.

Bronchial Neoplasms↗
PubMedDate not supplied

Debrisoquine metabolism and lung cancer risk.

Previous reports of the association between the debrisoquine metabolic polymorphism and lung cancer risk have been conflicting. We examined the hypothesis that the genetically determined ability to metabolize debrisoquine identifies individuals at increased risk for lung cancer in a study designed to address some of the methodological criticisms of previous studies. A case-control study of 335 incident Caucasian lung cancer patients and 373 controls matched for age, race, sex, and hospital, was conducted at the National Naval Medical Center (Bethesda, MD) and at the Laval Hospital (Sainte-Foy, Quebec, Canada). Debrisoquine metabolic phenotype was determined by debrisoquine administration and analysis of debrisoquine and 4-hydroxydebrisoquine in the subsequent 8-h urine collected. Stratified and logistic regression analyses were used to evaluate the association between extensive or intermediate debrisoquine metabolism and lung cancer risk. We found no increased risk among extensive or intermediate metabolizers (odds ratio, 0.6; 95% confidence interval, 0.3-1.2). The lack of an association was not confounded by control diagnoses, medications used within 1 month of debrisoquine administration, smoking, stage, or histology of lung cancer. No relationship was found among either heavy smokers or light and nonsmokers. Our results do not support the role of debrisoquine metabolism as a marker for lung cancer risk. While the concept that polymorphisms of metabolism may account for differential susceptibility to lung cancer is sound, debrisoquine metabolic phenotype was not associated with lung cancer risk in these data.

Aged↗