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Biomedical subjects

M B Orringer

Publications and source records attributed to M B Orringer.

At least 55 records · Page 3Linked to original sources
PubMed1995

Incidence and distribution of distant metastases from newly diagnosed esophageal carcinoma.

BACKGROUND: It is important to diagnose distant metastases disease in patients with newly diagnosed esophageal carcinoma, so that unwarranted surgery and its attendant risks are avoided. The purpose of this study was to determine (1) the percentage of esophageal cancer patients with distant metastases (M1) at presentation, (2) the locations of these distant metastases, and (3) how the metastases were diagnosed. METHODS: All patients at the University of Michigan Medical Center with newly diagnosed esophageal cancer between 1982 and July, 1993, were identified. Records for these 838 patients were reviewed, and patients were classified as having M0 or M1 disease at presentation. For patients with M1 disease, the locations of distant metastases and the methods of diagnosis were recorded. RESULTS: One hundred forty-seven of 838 (18%) patients had M1 disease. In 110 of 147 (75%) patients, M1 disease was detected before surgery via imaging or physical examination, including 102 of 147 (69%) via chest or abdominal computed tomography (CT). In no case staged as M0 by abdominal and chest CT was M1 disease detected on bone scan or head CT. Distant metastases were most commonly diagnosed in abdominal lymph nodes (45%), followed by liver (35%), lung (20%), cervical/supraclavicular lymph nodes (18%), bone (9%), adrenal (5%), peritoneum (2%), brain (2%), and stomach, pancreas, pleura, skin/body wall, pericardium, and spleen (each 1%). CONCLUSION: A significant percentage of patients with esophageal cancer have M1 disease at presentation. Imaging of the chest and abdomen is an effective method of screening such patients for M1 disease before treatment.

Adenocarcinoma↗
PubMed1995

Catastrophic complications of the cervical esophagogastric anastomosis.

Recent enthusiasm for the cervical esophagogastric anastomosis has arisen because of its perceived low morbidity. Although catastrophic complications of a cervical esophagogastric anastomosis are unusual, they can and do occur, and prevention is possible if the potential for them is recognized. Among 856 patients undergoing a cervical esophagogastric anastomosis after transhiatal esophagectomy, catastrophic cervical infectious complications occurred in 11 patients (1.3%): vertebral body osteomyelitis (1), epidural abscess with neurologic impairment (2), pulmonary microabscesses from internal jugular vein abscess (1), tracheoesophagogastric anastomotic fistula (1), and major dehiscence necessitating anastomotic takedown (6). These complications became manifest from 5 to 85 days after the esophageal resection and reconstruction (mean 19 days). Leakage from a gastric suspension stitch placed in the anterior spinal ligament over the vertebral bodies resulted in a posterior gastric leak and either osteomyelitis or an epidural abscess in three patients, none of whom had evidence of extravasation on the routine barium swallow 10 days after operation. Cervical exploration for a presumed anastomotic leak led to the unexpected discovery of an abscess formed by the stomach and the adjacent wall of the internal jugular vein, which was ligated and resected. One patient without symptoms who was discharged from the hospital with a contained anastomotic leak on the postoperative barium swallow was readmitted 7 days later with a cervical tracheoesophagogastric anastomotic fistula of which he ultimately died. In 6 patients (7% of those who had anastomotic leaks) there was sufficient gastric ischemia or necrosis, or both, to necessitate takedown of the anastomosis and intrathoracic stomach, cervical esophagostomy, and insertion of a feeding tube. As a result of this experience, it is recommended that cervical gastric suspension sutures either be omitted entirely or placed in the fascia over the longus colli muscles anterior to the spine, but not directly into the prevertebral fascia overlying the vertebral bodies or cervical disks. All but minute cervical anastomotic leaks, even if apparently contained, are best drained rather than treated expectantly. Patients who remain febrile and ill after bedside drainage of a cervical esophagogastric anastomosis leak should undergo cervical reexploration in the operating room; major gastric ischemia or necrosis, or both, may warrant takedown of the anastomosis and intrathoracic stomach.

Abscess↗
PubMed1995

Intrathoracic esophageal perforation. The merit of primary repair.

Between 1976 and 1993, 22 patients with intrathoracic esophageal perforations, none associated with carcinoma, underwent primary repair regardless of the interval between perforation and the time of repair. Eighteen perforations were iatrogenic and four were spontaneous. The interval from perforation to operation was less than 12 hours in 10 patients, 12 to 24 hours in 3, and more than 24 hours in 9. Principles of repair included (1) a local esophagomyotomy proximal and distal to the tear to expose the mucosal defect and normal mucosa beyond, (2) debridement of the mucosal defect and closure over a bougie, and (3) reapproximation of the muscle. The repair was buttressed with muscle or pleura in five patients. Associated distal obstruction caused by reflux stricture was treated with dilation and fundoplication in four patients. Of the four patients with achalasia, two underwent esophagomyotomy with a fundoplication and one underwent myotomy alone. There was one death. The esophageal repair healed primarily in 17 patients (80%). Four patients, three of whom underwent repair more than 24 hours after the perforation, had leaks at the site of repair. All four fistulas eventually healed with drainage alone, two with simple tube thoracostomy and two with rib resection and empyema tube placement. In the absence of cancer or an irreversible distal obstruction, meticulous repair of an intrathoracic esophageal perforation is the preferred approach, regardless of the duration of the injury, inasmuch as primary healing is likely, and the morbidity associated with prolonged drainage or diversion may be avoided.

Adult↗
PubMed1995

Expression and activation of erbB-2 and epidermal growth factor receptor in lung adenocarcinomas.

ErbB-2 and EGFR (epidermal growth factor receptor) are expressed in lung adenocarcinomas and associated with a poor prognosis. Immunocytochemical analysis revealed erbB-2 and EGFR coexperession as a characteristic feature of most lung adenocarcinomas, and at levels of receptor expression present in bronchial epithelial cells. In primary lung tumours and cell lines, erbB-2 detected using Western blot analysis demonstrated low-level phosphotyrosine staining of the 185 kDa band, as compared with breast cancer cell lines. A549 and A427 lung adenocarcinoma cells treated with neu differentiation factor (NDF) showed increased erbB-2 phosphotyrosine staining, but to a much lesser extent than breast cancer cells. The lung cells were examined for expression of the potential autocrine growth factors NDF and transforming growth factor alpha (TGF-alpha) by Northern blot analysis. Both NDF and TFG-alpha mRNA were abundantly expressed in the A549 cells. NDF mRNA was highest during active cell proliferation and decreased in confluent cells or after treatment with the growth-inhibitory steroid dexamethasone. Primary tumours and cell lines expressed EGFR, showing higher basal level phosphotyrosine staining than erbB-2. Treatment with NDF and EGF (epidermal growth factor) stimulated cell growth, and in A549 cells the presence of both factors provided an additive increase in cell growth. The growth stimulus that ligand-activated erbB-2 and EGFR provides to lung adenocarcinoma cells may establish a background of continued cell proliferation over which other critical transforming events may occur.

Adenocarcinoma↗
PubMed1995

E-cadherin expression in primary and metastatic thoracic neoplasms and in Barrett's oesophagus.

Reduced expression of E-cadherin, a Ca(2+)-dependent cell adhesion molecule present in normal epithelium, has been associated with invasive and metastatic cancer. Immunohistochemistry was used in examining the relationship between E-cadherin expression and stage in 59 oesophageal and 52 lung cancers. Advanced-stage oesophageal cancers were associated with both reduced and disorganised E-cadherin expression (P < 0.01). Advanced-stage lung adenocarcinomas generally exhibited disorganised or reduced E-cadherin expression, but no statistical association between expression pattern and stage was found (P > 0.05). No differences in stage were seen between tumours with reduced or disorganised E-cadherin expression. Altered E-cadherin expression was detected in dysplastic, non-invasive Barrett's oesophagus. Importantly, high-level E-cadherin expression was detected in 17 of 17 lymph nodes containing metastatic cancer. E-cadherin mRNA expression was decreased in tumours with reduced protein expression, but not in tumours with disorganised expression. Expression of alpha-catenin mRNA, an E-cadherin-associated protein, was detected in tissues with altered E-cadherin protein expression. Reduced and disorganised expression of E-cadherin appear to be related to transcriptional and post-translational events respectively, and both appear to represent altered cell adhesion associated with invasion and metastasis in thoracic neoplasms.

Adenocarcinoma↗
PubMed1995

Stenosis of the central airways: evaluation by using helical CT with multiplanar reconstructions.

PURPOSE: To assess the accuracy of helical computed tomography (CT) with multiplanar reconstructions (MPRs) in the evaluation of stenoses of the central airways. MATERIALS AND METHODS: Thin-section axial CT and helical CT with MPRs were used to examine the central tracheobronchial tree for the presence of stenosis in 27 patients who underwent lung transplantation and 17 nontransplantation patients. The findings from these modalities were then compared with the findings obtained at conventional tomography and bronchoscopy, when available. RESULTS: Axial CT alone was 91% accurate in depicting stenosis, CT with MPRs was 94% accurate, and conventional tomography was 89% accurate in the evaluation of bronchial anastomosis in transplant recipients. CT and CT scans with MPRs were each 91% accurate in depicting stenosis in nontransplantation patients; the single false-negative finding showed focal tracheomalacia at bronchoscopy. CONCLUSION: CT with MPRs may be more accurate than thin-section axial CT in the demonstration of mild stenosis, the length of a stenosis, and horizontal webs.

Anastomosis, Surgical↗
PubMed1995

Helical computed tomography for the evaluation of tracheal stenosis.

BACKGROUND: Helical computed tomography with multiplanar reconstruction (CT/MPR) was used to study proximal airway stenosis. METHODS: Twenty-eight helical CT/MPR studies were obtained in 25 patients with known or suspected stenosis of the trachea or main bronchi. Computed tomographic results were compared with planar tomograms and bronchoscopic evaluation of the airway. RESULTS: CT/MPR accurately demonstrated the site and degree of tracheal and main bronchial stenoses with a sensitivity of 93%, a specificity of 100%, and an accuracy of 94%. There was one false negative study in a patient with tracheomalacia. In a second patient, a tracheal web was only apparent on nonstandard viewing windows. CONCLUSIONS: CT/MPR provides good anatomic detail and is an increasingly available technique. Potential drawbacks include the need for a longer breath-hold (15 to 45 seconds) and increased complexity of data compared with conventional tomograms. Helical CT/MPR is useful in the preoperative evaluation of these patients and, as experience accumulates, may replace the use of conventional tomograms.

Bronchial Diseases↗
PubMed1995

Esophageal carcinoma metastatic to the brain: clinical value and cost-effectiveness of routine enhanced head CT before esophagectomy.

PURPOSE: To assess the value of screening enhanced head CT before esophagectomy for carcinoma, identify increased risk factor(s) for brain metastases, and determine metastasis incidence. METHODS: Thoracic surgery files of patients undergoing esophagectomies for squamous carcinomas, adenocarcinomas, and undifferentiated carcinomas between January 1984 and March 1993 were reviewed regarding sex, size (length) of neoplasm, and brain metastases. Surgical pathology and tumor registry files also were reviewed. Records of patients with brain metastases were reviewed in detail. RESULTS: Three hundred thirty-four esophagectomies were performed for 230 adenocarcinomas (202 male, 28 female) and 104 squamous carcinomas (61 male, 43 female). In 9 males and 1 female with adenocarcinomas and 1 male and 1 female with squamous carcinomas, brain metastases developed. Surgical pathology files identified 293 additional esophageal carcinomas, including 2 males with adenocarcinomas metastatic to brain. Tumor registry files identified I additional male with brain metastasis from an undifferentiated esophageal neoplasm. No statistically significant preoperative characteristic of esophageal carcinomas with proneness to brain metastases was found, except large size of primary neoplasm. Preoperative screening head CT done on approximately 240 patients who underwent esophagectomies showed no metastases. CONCLUSIONS: Brain metastases from carcinomas of the esophagus are relatively uncommon (3.6% in the esophagectomy cohort). They tend to occur in patients with large primary neoplasm, probably especially adenocarcinomas involving the esophagogastric junction, and with findings of local invasion and lymph node metastases by CT and/or microscopically. It may be reasonable to obtain head CT as a last preoperative staging procedure in such patients. Routine preoperative head CT for staging is not cost effective.

Aged↗
PubMed1994

Inhibition of interleukin 8 attenuates angiogenesis in bronchogenic carcinoma.

We investigated the role of interleukin 8 (IL-8) in mediating angiogenesis in human bronchogenic carcinoma. Increased quantities of IL-8 were detected in tumor tissue as compared with normal lung tissue. Immunohistochemical staining of tumors revealed primary localization of IL-8 to individual tumor cells and demonstrated the capacity of tumor to elaborate IL-8. Functional studies that used tissue homogenates of tumors demonstrated the induction of both in vitro endothelial cell chemotaxis and in vivo corneal neovascularization. It is important to note that the addition of neutralizing antisera to IL-8 to these assays resulted in the marked and specific attenuation of these responses. Our observations definitively establish IL-8 as a primary mediator of angiogenesis in bronchogenic carcinoma and offer a potential target for immunotherapies against solid malignancies.

Animals↗
PubMed1994

Intestinal differentiation and p53 gene alterations in Barrett's esophagus and esophageal adenocarcinoma.

The development of esophageal adenocarcinoma is frequently associated with intestinal-type Barrett's metaplasia. Barrett's metaplasia and esophageal adenocarcinomas were examined for expression of the intestinal brush-border-associated hydrolase aminopeptidase N (APN). APN mRNA was detected by utilizing the reverse transcription polymerase chain reaction (RT-PCR) in 50% of Barrett's metaplasia specimens and in 26% of esophageal adenocarcinomas. APN protein was detected by utilizing immunohistochemistry in 84% of Barrett's metaplasia specimens and in 71% of adenocarcinomas, although a decrease or loss of APN protein was sometimes observed in dysplastic Barrett's metaplasia and adenocarcinomas. Alterations in the p53 tumor-suppressor gene have previously been found in both dysplastic Barrett's mucosa and esophageal adenocarcinomas. The same specimens analyzed for APN were examined for the nuclear accumulation of the p53 protein. Utilizing immunohistochemistry, p53 staining was detected in 42% of Barrett's metaplasia specimens, most of which were dysplastic, and in 58% of adenocarcinomas. In the samples positive for p53 protein, gene mutations in exons 5, 7 and 8 were detected by utilizing single-strand conformation polymorphism analysis (SSCP) in 1 Barrett's metaplasia specimen and 6 adenocarcinomas. In Barrett's metaplasia, there was an inverse correlation between APN protein expression and p53 protein accumulation (p < 0.05) suggesting a link between genetic alterations and loss of this marker. The analysis of markers of intestinal differentiation with markers of disease progression may prove to be a useful approach for studying carcinogenesis in Barrett's metaplasia.

Adenocarcinoma↗
PubMed1994

Selective lung or heart-lung transplantation for pulmonary hypertension associated with congenital cardiac anomalies.

Fixed pulmonary hypertension has been a contraindication to correction of congenital heart defects. Beginning in February 1991, we pursued a policy of performing single-lung transplantation with intracardiac repair for selected patients with this physiology, reserving heart-lung transplantation for those with unreconstructable heart disease. Of 7 patients treated under this protocol, 5 underwent single-lung transplantation and intracardiac repair. The cardiac anomalies included complete atrioventricular canal (1), aortopulmonary window (1), atrial septal defect (1), and ventricular septal defect (2). One patient died perioperatively. All 4 patients surviving operation remained alive through the first postoperative year, but 3 died 13, 17, and 22 months after operation. Two other patients with pulmonary hypertension (1 with tricuspid atresia, 1 after failed Mustard procedure) received a heart-lung transplant and are well 15 and 18 months after operation. This experience demonstrates that selected patients with major intracardiac defects and pulmonary hypertension may have good early results after cardiac repair and single-lung transplantation, but that long-term results are considerably less favorable.

Adolescent↗
PubMed1994

Staging of mediastinal non-small cell lung cancer with FDG PET, CT, and fusion images: preliminary prospective evaluation.

PURPOSE: To evaluate use of positron emission tomography (PET) with 2-[fluorine-18]-fluoro-2-deoxy-D-glucose (FDG) in detection of mediastinal lymph node metastases from non-small cell lung cancer. MATERIALS AND METHODS: A prospective trial to compare FDG PET and computed tomography (CT) of the thorax was performed in 23 patients with newly diagnosed or suspected non-small cell lung cancer. Blinded interpretations of CT alone, PET alone, CT and PET together, and fusion images were performed, and the results were compared with pathologic results. RESULTS: Nineteen of 23 patients had non-small cell lung cancer. Prevalence of mediastinal involvement was 41%. In staging disease in the mediastinum, CT alone was 64% sensitive, 44% specific, and 52% accurate, whereas PET alone and fusion images were 82% sensitive, 81% specific, and 81% accurate (P < .05). CONCLUSIONS: FDG PET was more accurate than CT in staging disease in the mediastinum in patients with lung cancer and appears to be the preferred imaging method in this clinical setting.

Carcinoma, Non-Small-Cell Lung↗
PubMed1994

Alterations of K-ras, p53, and erbB-2/neu in human lung adenocarcinomas.

The development of human adenocarcinoma of the lung involves multiple genetic changes including activation of oncogenes and loss of tumor suppressor genes. Patients whose lung tumors contain K-ras oncogene mutation, accumulation of the protein product of the tumor suppressor gene p53, or erbB-2/neu oncoprotein overexpression have been shown to have a worse prognosis. We examined these three genetic indicators in 29 lung adenocarcinomas to determine whether these markers are present in the same tumors or if they represent molecular changes that define different subsets of patients. P53 nuclear protein accumulation and erbB-2/neu protein overexpression were determined by immunohistochemical analysis of cryostat sections of tumor specimens and corresponding normal lung tissue. K-ras mutations were detected by radiolabeled oligonucleotide probes, specific for the various twelfth codon mutations, hybridized to exon 1 of K-ras, which was amplified by the polymerase chain reaction. Increased nuclear accumulation of p53 protein was found in 11 adenocarcinomas (38%). All of the p53 positive tumors were found to show high level staining and homogeneous expression of erbB-2/neu protein. K-ras mutations were detected in seven tumors (24%), all of which overexpressed erbB-2/neu. The presence of a K-ras mutation did not correlate with p53 accumulation. In total, 93% of the tumors were found to overexpress erbB-2/neu, the highest being in one tumor with erbB-2/neu gene amplification. The presence of K-ras twelfth codon mutation was associated with increased cigarette smoking. In conclusion, erbB-2/neu overexpression is a common event in lung adenocarcinomas. Furthermore, the presence of K-ras mutation and p53 protein accumulation define separate groups of patients. The mechanisms by which these genetic alterations interact or adversely affect prognosis is unknown.

Adenocarcinoma↗
PubMed1994

Production of interleukin-10 by human bronchogenic carcinoma.

Interleukin-10 (IL-10) is a recently characterized cytokine with suppressive activity against various aspects of the cellular immune response. Our laboratory has previously demonstrated that another anti-inflammatory cytokine, IL-1 receptor antagonist (IRAP) is produced and secreted by human bronchogenic carcinomas. We speculated that tumor production of IRAP may mitigate host responses and confer increased tumor viability. In this study, we investigated the capacity of human bronchogenic tumors to produce IL-10 as another possible mechanism to attenuate host defenses. We found increased levels of antigenic IL-10 in tissue homogenates of human bronchogenic carcinomas compared with normal lung tissue (13.69 +/- 2.87 versus 5.84 +/- 0.84 ng/mg total protein). Immunohistochemical staining of tumors illustrate primary localization of antigenic IL-10 to individual tumor cells. Analysis of supernatants of several unstimulated human bronchogenic cell lines in vitro demonstrated the ability of tumor cells to constitutively produce IL-10. Functional studies of mononuclear cells, cultured in the presence of conditioned medium from a bronchogenic cell line, demonstrated their increased tumor necrosis factor and IL-6 production with the addition of neutralizing antibodies to IL-10. These findings demonstrate that human bronchogenic carcinomas elaborate functional IL-10, which may significantly impair immune effector cell function and enable the tumor to evade host defenses.

Carcinoma, Bronchogenic↗
PubMed1994

Achalasia. A morphologic study of 42 resected specimens.

Achalasia is characterized by failure of relaxation of the lower esophageal sphincter and absence of progressive peristalsis in the esophageal body. Few data are available regarding the morphologic features of achalasia, in particular its histologic progression. The esophagi of 42 patients with achalasia treated with total thoracic esophagectomy were examined histologically in order to systematically identify morphologic features of clinically unresponsive achalasia and to determine what could be learned about the disease's evolution. In all cases, myenteric ganglion cells within the esophageal body were markedly diminished, with 20 specimens having none. Twenty specimens had residual ganglion cells in the proximal esophagus, and 15 specimens had a few randomly distributed ganglion cells in the mid- and distal portions of the esophagus. Inflammation within myenteric nerves, present in all cases, generally consisted of a mixture of lymphocytes and eosinophils, occasionally with plasma and mast cells. Focal replacement of myenteric nerves by collagen occurred in all cases, and there was almost complete replacement in several cases. Actual destruction of the residual ganglion cells was not seen. The resected esophagi also shared extramyenteric morphologic features. Some features probably stemmed from physiologic obstruction, such as muscular hypertrophy, mainly of the muscularis propria (all cases), with secondary degeneration and fibrosis (29 cases), and eosinophilia of the muscularis propria (22 cases). Other changes, probably resulting from chronic stasis of ingested materials in the lumen, included diffuse squamous hyperplasia (all cases), lymphocytic mucosal esophagitis (28 cases), lymphocytic inflammation of the lamina propria and submucosa with prominent germinal centers (all cases), and submucosal periductal or glandular inflammation with complete loss of submucosal glands in half of the cases. One patient had high-grade squamous dysplasia, and another had superficially invasive squamous cell carcinoma. A third group of changes was probably due to previous esophagomyotomy, including abnormal gastroesophageal reflux, as shown by pH reflux testing (13 cases) and Barrett's mucosa (four cases). In one case of Barrett's there was low-grade dysplasia. Clinically unresponsive, surgically resected achalasia has almost total loss of ganglion cells, and widespread destruction of myenteric nerves has already occurred. The only active component is myenteric inflammation. However, it cannot be determined whether this inflammation is a manifestation of ongoing nerve destruction or whether it is a secondary phenomenon.

Adult↗