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Biomedical subjects

T V Colby

Publications and source records attributed to T V Colby.

At least 91 records · Page 5Linked to original sources

Cigarette smoking: a risk factor for idiopathic pulmonary fibrosis.

We conducted a multicenter case-control study of clinically and histologically diagnosed idiopathic pulmonary fibrosis (IPF), a chronic diffuse interstitial lung disease of unknown cause. The study included 248 cases, and 491 control subjects identified through random-digit dialing, matched to cases in sex, age, and geographic region. Telephone interviews were conducted with both cases and controls to collect information on potential risk factors for IPF, including smoking and household, occupational, and environmental exposures. Pulmonary function tests, X-rays, computed tomographic (CT) scans of the chest, and lung biopsy reports were submitted by referring centers to support the diagnoses. An a priori hypothesis that smoking is associated with IPF was examined with conditional logistic regression analyses. More cases (72%) than control subjects (63%) had a history of ever smoking. The odds ratio (OR) for ever smoking was 1.6 (95% CI: 1.1 to 2.4). Risk was significantly elevated for former smokers (OR = 1.9; 95% CI: 1.3 to 2.9) and for smokers with 21 to 40 pack-yr (OR = 2.3; 95% CI: 1.3 to 3.8). A history of smoking is associated with an increased risk for the development of IPF. Although there was no clear exposure-response pattern with cumulative consumption of cigarettes, there was a trend for time since cessation of smoking, with the highest risk for those who had most recently quit.

Adult↗

Acute eosinophilic pneumonia: histopathologic findings in nine patients.

Acute eosinophilic pneumonia is characterized by acute respiratory insufficiency, hypoxemia, fever, diffuse radiographic infiltrates, and eosinophilia in bronchoalveolar lavage fluid (BALF) or lung biopsies in the absence of infection, atopy, or asthma. A rapid response to corticosteroids is characteristic. We reviewed our experience with nine cases of acute lung disease with histologic features of acute and organizing diffuse alveolar damage and prominent interstitial and alveolar eosinophils in order to determine whether this pathology was characteristic of acute eosinophilic pneumonia. The mean age of the patients (four men and five women) was 53 yr (range: 33 to 71 yr). They presented with 2 to 21 d of dyspnea, cough, myalgias, and fever. All were hypoxic and had bilateral infiltrates on chest radiographs. Peripheral blood eosinophilia was present in four of eight patients (peripheral blood count unavailable for one patient). All patients were treated with high-dose corticosteroids with a mean time to symptomatic and radiographic improvement of 4 d. Seven of the nine patients enrolled in the study are alive without relapse; one patient has a mild deficit in diffusing capacity, and one patient died of a myocardial infarct while improving on therapy. The presence of eosinophils in cases of acute respiratory insufficiency due to diffuse alveolar damage (DAD) should suggest the diagnostic possibility of acute eosinophilic pneumonia. Acute eosinophilic pneumonia should be distinguished from other causes of DAD because of important differences in natural history.

Acute Disease↗

Carcinoma of the stomach with hepatocyte differentiation (hepatoid adenocarcinoma).

A case of hepatoid adenocarcinoma of the stomach is reported, and the literature is reviewed. The stomach is one of the most common sites in which hepatoid adenocarcinomas have been detected. Of the 59 cases reviewed from the literature (including the current case), a 2:1 male predominance was noted, and the serum alpha-fetoprotein level was almost always increased. All patients were adults, and most had evidence of metastases at the time of resection. Prognosis seems less favorable than that associated with the more common intestinal type of adenocarcinoma of the stomach. Hepatoid adenocarcinomas typically show periodic acid-Schiff-positive, diastase-resistant intracytoplasmic globules, which are demonstrated to be positive with antibodies to alpha-fetoprotein. The tumor cells resemble liver cells, and rare cases, including our own, have evidence of bile production. In our case, messenger RNA for albumin, unique to liver cells, was demonstrated by in situ hybridization of the tumor cells.

Adenocarcinoma↗

Idiopathic bronchiolitis obliterans organizing pneumonia/cryptogenic organizing pneumonia with unfavorable outcome: pathologic predictors.

Idiopathic bronchiolitis obliterans organizing pneumonia (BOOP) and cryptogenic organizing pneumonia (COP) are synonyms for an inflammatory interstitial process characterized by young fibromyxoid connective tissue within airways and air spaces. This clinicopathologic condition is associated with an excellent response to steroidal therapy in more than 80% of patients. In this study, we examined matched groups of 10 patients with steroid-responsive idiopathic BOOP/COP and 9 patients with idiopathic BOOP/COP who fared poorly despite therapy. No significant differences in demographics, symptoms, or radiographic appearances were noted between the two cohorts. Histologic examination revealed that the cases with progressive, idiopathic BOOP/COP were accompanied by scarring and remodeling of the background lung parenchyma in 89% of cases, in contrast to 10% of those with a good prognosis. This finding provided a potential morphologic marker of outcome for therapy in idiopathic BOOP/COP. Steroid-nonresponsive cases of BOOP/COP may have a propensity to cause irreversible injury to the lung, a feature not seen in cases with a good outcome. Another explanation may be that such cases represent a BOOP/COP-like reaction pattern in patients with an associated fibrosing interstitial pneumonia, especially usual interstitial pneumonia. The differential diagnosis of BOOP/COP with organizing diffuse alveolar damage, eosinophilic pneumonia, and other chronic interstitial pneumonias is discussed.

Adrenal Cortex Hormones↗

DNA ploidy and protein content in bronchioloalveolar carcinoma multi-variable flow cytometry.

Multi-variable flow cytometry studies were done on paraffin-embedded surgical specimens from 97 patients with bronchiolalveolar carcinoma (BAC) and on 10 normal lung tissue specimens to assess the value of nuclear protein content besides DNA ploidy. Tumor tissues were stained for DNA content with propidium iodide and for protein content with fluorescein isothiocyanate. DNA ploidy measurements were successful in 87 of the 97 specimens. Twenty-four (28%) specimens were DNA diploid, and 63 (72%) were DNA nondiploid (DNA tetraploid or DNA aneuploid). There was no significant difference in survival between patients with DNA diploid and with DNA nondiploid tumors (P = 0.69). The protein histogram pattern was bimodal in 26/87 (30%) of patients; these had significantly shorter survival than patients with either normal or right-shift protein histogram patterns (61/87) (P = 0.0033). The nuclear protein measurement was an independent prognostic indicator when corrected for tumor grade and tumor size in a Cox model analysis (P = 0.04). The nuclear protein measurement correlated with nuclear size as determined by nuclear volume measurements. The combination of DNA ploidy, protein, and cell size measurements by flow cytometry provide a useful biologic basis for the variable prognosis seen with BAC tumors.

Adenocarcinoma, Bronchiolo-Alveolar↗

Post-irradiation malignant mesothelioma.

BACKGROUND: Approximately 30 patients with malignant mesothelioma following radiotherapy have been described. Population-based studies of this occurrence have not been reported. METHODS: Patients with malignant mesothelioma of the pleura were collected. All of the patients had a prior cancer and had received radiotherapy to the region in which the malignant mesothelioma developed. Data from the National Cancer Institute's Surveillance, Epidemiology and End Results Program and the Connecticut Tumor Registry were evaluated for cases of malignant mesothelioma of the pleura occurring in patients with a previous cancer. The literature on post-irradiation malignant mesotheliomas was reviewed. RESULTS: Eight patients (4 men, 4 women) with malignant mesothelioma occurring in sites of radiotherapy for a prior tumor were identified. The mean age at diagnosis of mesothelioma was 45 years (range: 22-78 years), and the average interval between radiotherapy and the mesothelioma was 21 years (range: 11-29 years). Three of the patients had also received chemotherapy. Histologically, the mesotheliomas were epithelial in five cases, biphasic in one, and sarcomatous in one. One hundred forty-two patients were identified in the epidemiologic survey. The majority were men (89%), with a mean age for all patients of 68.5 years (range: 35-86 years) and a median latency between first cancer and mesothelioma of 4.3 years (range: 2 months-29.9 years). CONCLUSIONS: Mesotheliomas rarely develop as second malignant neoplasms. Within a large, population-based survey of patients with cancer, temporal patterns and demographic features of most second primary mesotheliomas were similar to asbestos-related tumors, although the late effects of cancer treatment might have contributed to the occurrence of cancer in some patients.

Adult↗

Lung tumors with a rhabdoid phenotype.

Six malignant tumors of the lung with a rhabdoid phenotype are described. All presented as lung masses in middle-aged to elderly adults (mean age 51 years), with no sex predilection. The tumors ranged from 1.3 cm to 8.0 cm in size and were generally associated with locally advanced disease. The distinctive (and defining) histologic feature was the presence of macronucleolated tumor cells with a large eosinophilic globular cytoplasmic inclusion. These "rhabdoid" elements comprised at least 10% of the neoplastic population. Immunohistochemistry revealed diffuse vimentin positivity in all cases. Epithelial and neuroendocrine markers were at least focally positive in five and in all six cases, respectively. Electron microscopy was performed in one case and it showed paranuclear aggregates of intermediate filaments, dense core granules, and intercellular attachments. Malignant tumors of the lung with a rhabdoid phenotype are very rare. The majority are poorly differentiated carcinomas, and they frequently show features suggesting a neuroendocrine differentiation.

Adult↗

Biphasic synovial sarcomas arising in the pleural cavity. A clinicopathologic study of five cases.

Five cases of primary synovial sarcoma of the pleura are presented with a discussion of differentiation from other biphasic malignant neoplasms, most notably malignant mesothelioma. The cases have clinical, histologic, and immunohistochemical features consistent with synovial sarcoma of soft tissue. The average age at initial presentation of the reported patients was 25 years with an approximate range of 9 to 50 years. A large pleural-based intrathoracic mass was identified in each case. Histologic analysis showed a biphasic (mixed) pattern composed of epithelial and spindle cells. The epithelial cells showed cleft-like to tubulopapillary growth with focal intraluminal periodic acid Schiff's (PAS)-positive, diastase-resistant secretions identified in four of the five cases. The spindle cell component was composed predominantly of densely packed, elongated, fusiform cells. Immunohistochemical staining showed positivity with antibodies against cytokeratin, BER.EP4, epithelial membrane antigen, and vimentin in all cases. The patients seem to have an aggressive course, with four deaths reported within 3 years from initial surgery. These cases represent the first reported cases of primary synovial sarcoma of the pleura and lend further credence to the theory that synovial sarcomas are derived from immature mesenchymal elements, not from synovium.

Adolescent↗

Hodgkin's disease and lymphoproliferations resembling Hodgkin's disease in patients receiving long-term low-dose methotrexate therapy.

Recently, it has been shown that patients with rheumatologic diseases who are treated with methotrexate can develop immunosuppression-associated lymphoproliferative disorders. Although a variety of lymphoproliferations have been described in the setting of methotrexate therapy, only rare cases of Hodgkin's disease (HD) have been reported. In this study, we provide a more complete characterization of the spectrum of lymphoproliferations that resemble HD or show features diagnostic of HD that occur in patients receiving long-term low-dose methotrexate therapy. Eight patients were receiving methotrexate for various disorders. Four cases were considered to represent lymphoproliferations resembling HD; the other four cases were diagnosed as HD because they showed diagnostic morphologic and immunophenotypic features. All three patients with lymphoproliferations resembling HD on whom follow-up was available experienced tumor regression with methotrexate withdrawal or with methotrexate withdrawal and steroids; none of these three patients required further therapy. All three patients with HD on whom follow-up was available are alive and free of disease following chemotherapy or radiation therapy. In two of these patients, the tumor persisted or progressed despite discontinuation of methotrexate with observation; the third patient received chemotherapy at the same time methotrexate was stopped. Our findings indicate that a spectrum of lymphoproliferations resembling HD or diagnostic of HD can occur in patients receiving long-term low-dose methotrexate therapy. Recognition of these lymphoproliferative disorders is clinically important because a subset of these neoplasms will completely resolve with discontinuation of methotrexate, thereby obviating the need for chemotherapy or radiation therapy.

Aged↗

Lung nodule enhancement at CT: prospective findings.

PURPOSE: To determine if lung nodule enhancement measured with computed tomography (CT) is directly related to the likelihood of malignancy and to nodule vascularity. MATERIALS AND METHODS: Radiologically indeterminate 7-30-mm pulmonary nodules were studied in 107 patients with malignant neoplasms (n = 52), granulomas (n = 51), and benign neoplasms (n = 4). Attenuation was recorded from serial thin-section CT scans before and after injection of contrast material. Twenty-four histologic specimens were graded after immunoperoxidase vascular staining with antibody to factor VIII-associated antigen. RESULTS: Malignant neoplasms were enhanced (median, 46.5 HU; range, 11-110 HU) statistically significantly more than granulomas and benign neoplasms (median, 8 HU; range, -10 to 94 HU) (P < .001). With 20 HU as the threshold for a positive test result, the sensitivity was 98%, specificity was 73%, and accuracy was 85% (prevalence of malignancy, 49% ¿52 of 107 nodules]). The degree of enhancement was statistically significantly related to the amount of central vascular staining (P < .001). CONCLUSION: Enhancement appears to be an indicator of malignancy and vascularity. These prospective findings corroborate previously reported results.

Adult↗

Tissue localization of transforming growth factor-beta1 in pulmonary eosinophilic granuloma.

Pulmonary eosinophilic granuloma is characterized by infiltration of the lungs with fibronodular lesions containing specialized Langerhans' cells. In some patients, progressive pulmonary fibrosis leads to significant respiratory impairment. Transforming growth factor-beta1 (TGF-beta1) promotes fibrosis by enhancing the synthesis of extracellular matrix components. The role of TGF-beta1 in promoting fibrosis in the setting of pulmonary eosinophilic granuloma is currently unknown. We used immunohistochemistry to evaluate the extent and distribution of TGF-beta1 and the extracellular matrix components type I collagen and decorin, a TGF-beta1-binding proteoglycan. Lung biopsies from 11 patients with pulmonary eosinophilic granuloma were evaluated. In biopsies with active inflammatory lesions containing Langerhans' cells, hyperplastic type 2 pneumocytes and alveolar macrophages within and surrounding the fibronodular lesions contained abundant TGF-beta1. Langerhans' cells were consistently devoid of immunoreactive TGF-beta1. Active inflammatory lesions also exhibited staining for decorin, in a loosely organized distribution. Advanced fibrotic lesions of eosinophilic granuloma, containing minimal inflammatory cells and few or no Langerhans' cells, exhibited weak or absent staining for TGF-beta1 within either hyperplastic type 2 pneumocytes or alveolar macrophages. The fibroconnective tissues of these advanced fibrotic lesions consistently revealed dense staining for decorin. Through their actions on extracellular matrix protein accumulation, TGF-beta1 and the TGF-beta1-binding proteoglycan decorin may modulate fibrotic repair accompanying pulmonary eosinophilic granuloma.

Collagen↗

p53 mutations and occupational exposures in a surgical series of lung cancers.

p53 mutations are frequent in malignant lung tumors. Of 88 surgically treated lung cancers from cigarette smokers previously evaluated for p53 mutations, 45 tumors (51.1%) had mutations in exons 5-8 (D. G. Guinee, Jr. et al., Carcinogenesis (Lond.), 16: 993-1002, 1995). We report here the examination of 13 occupational exposures and 13 high-risk occupations in relation to these p53 mutations. Two molecular abnormalities were associated with occupational exposures: (a) G:C-->T:A transversions on the coding (nontranscribed) strand (n = 13) were associated with chromate exposure and employment in the metal industry (P < 0.05) and marginally associated with nickel exposure (P = 0.056); and (b) G:C-->A:T transitions at non-CpG sites (n = 9) were associated with work in the petrochemical industry (P = 0.05). No association was found between p53 mutations and gender, cigarette pack-years, tumor histology, age at diagnosis, or family history of lung cancer. Because all three chromate-exposed subjects had large cell carcinomas exhibiting G: C-->T:A coding-strand transversions, follow-up of a cohort with this exposure should clarify the association with the p53 gene.

Adult↗

Anti-p53 antibodies in sera from patients with chronic obstructive pulmonary disease can predate a diagnosis of cancer.

Serum anti-p53 antibodies (p53-Abs) may be surrogate markers for both p53 alterations and preclinical cancer. Ancillary to a prospective trial to abate progressive development of clinical stages of chronic obstructive pulmonary disease, we conducted a retrospective, nested case-control study. Twenty-three cases were diagnosed with cancer during the trial. Enzyme immunoassay, immunoblotting, and immunoprecipitation were used to detect p53-Abs in serum, immunohistochemistry (IHC) to detect p53 accumulation, and single-strand conformation polymorphism and DNA sequencing to detect p53 mutations in tumor samples. p53-Abs were detected by three types of assays in five (23%) of the cancer patients, 80% of whom had detectable p53-Abs before diagnosis: 2 lung cancers (7 and 6 months before), 1 prostate cancer (11 months), and 1 breast cancer (5 months). Four Ab-positive patients had IHC-positive tumors. Two of 4 Ab-positive patients and 2 of 14 Ab-negative had p53 missense mutations or base pair deletion and IHC-positive tumors. The 44 noncancer COPD controls, matched with the cancer cases for age, gender, and smoking habits, were negative for p53-Abs. These results indicate that p53-Abs may facilitate the early diagnosis of cancer in a subset of smokers with chronic obstructive pulmonary disease who are at an increased cancer risk.

Aged↗

Middle lobe syndrome: a clinicopathological study of 21 patients.

Middle lobe syndrome (MLS) is an uncommon lung disorder involving the right middle lobe and/or lingula and is characterized by a spectrum of clinical and pathological lesions ranging from recurrent atelectasis or pneumonias to bronchiectasis. Despite several series reporting the clinical features of MLS, histopathological descriptions are rare. We reviewed the clinical characteristics and pathological findings in 21 patients with MLS who underwent surgical resections. Six male and 15 female patients between the ages of 5 and 80 years (mean, 47 years) were studied. All patients were symptomatic and complained of chronic cough (8), hemoptysis (6), chest pain (4), dyspnea (3), or fever (2). The right middle lobe was involved in 11 patients, the lingula in four patients, and both right middle lobe and lingula in six patients. Chest radiographs, bronchograms, and/or computed tomography scans were available for review in 19 patients and showed consolidation (8), bronchiectasis (9), patchy infiltrates (5), and atelectasis (4) in various combinations. Pathological findings included bronchiectasis in 10 patients, chronic bronchitis/bronchiolitis with lymphoid hyperplasia in seven, patchy organizing pneumonia in six, atelectasis in five, granulomatous inflammation in five, and abscess formation in four. Three patients with granulomatous inflammation had associated atypical mycobacterial infection. Broncholithiasis was confirmed by pathological examination in one patient. No pathological cause for bronchial obstruction was identified in the remaining 20 patients, although one was thought to have had broncholithiasis on the basis of preoperative bronchoscopy. The presence of bronchiectasis, bronchitis or bronchiolitis, organizing pneumonia, or atelectasis in specimens from the right middle lobe or of lingula in the absence of an identifiable cause of bronchial obstruction should suggest a diagnosis of MLS.

Adolescent↗

Pathologic comparison of video-assisted thoracic surgical lung biopsy with traditional open lung biopsy.

Video-assisted thoracic surgical lung biopsy is an alternative to traditional open lung biopsy for diagnosis in patients with pleuropulmonary diseases. Between January 7, 1991, and August 3, 1993, 71 consecutive patients had video-assisted thoracic surgical lung biopsy and 42 patients had traditional open lung biopsy. A specific histologic diagnosis that correlated with the clinical findings was sought in each case and the yield was compared between the two groups. Procedure-related artifactual changes were also evaluated; the extent of traumatic hemorrhage and neutrophil margination as a result of tissue manipulation was significantly greater for patients in the video-assisted thoracic surgical lung biopsy group than for those in the open lung biopsy group, but the changes were generally minor and did not affect diagnostic yield. Complications developed in 11 (15%) of 71 patients in the video-assisted thoracic surgical lung biopsy group including 5 patients with prolonged air leakage (more than 10 days); 2 with pneumonia; and 1 each with bleeding, late pneumothorax necessitating readmission, mucus plug necessitating bronchoscopy, and a hypoxic episode necessitating mechanical ventilation. On the other hand, 7 (17%) of 42 patients in the open lung biopsy group had complications including 4 patients with prolonged air leakage (more than 10 days) and 3 with pneumonia. There were 6 (8%) operative deaths in patients who had video-assisted thoracic surgical lung biopsy and 7 (17%) in the open lung biopsy group; all had preoperative respiratory failure. We conclude that video-assisted thoracic surgical lung biopsy is an acceptable alternative to open lung biopsy for diagnosis of pulmonary infiltrates or indeterminate nodules.

Adult↗

Critical commentary.

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Carcinoma, Squamous Cell↗