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Biomedical subjects

M B Orringer

Publications and source records attributed to M B Orringer.

At least 91 records · Page 5Linked to original sources
PubMed1992

Expression and regulation of human pulmonary fibroblast-derived monocyte chemotactic peptide-1.

Monocyte recruitment is essential for maintenance of normal pulmonary macrophage populations. In addition, acute and chronic inflammatory pulmonary diseases are associated with sequestration of mononuclear phagocytes in the lung. Although alveolar macrophages (AM phi) can secrete a number of potent inflammatory and chemoattractment mediators, these immune cells do not produce monocyte chemotactic peptide (MCP-1) in response to lipopolysaccharide (LPS), tumor necrosis factor (TNF), or interleukin-1 beta (IL-1 beta). The pulmonary fibroblast (PF) may play a pivotal role in monocyte recruitment. In these studies, we demonstrate a time- and dose-dependent production of PF-derived steady-state MCP-1 mRNA, MCP-1 antigen, and monocyte chemotactic bioactivity attributable to MCP-1. In cellular models examining cytokine networks between AM phi and PF, LSP-stimulated AM phi (conditioned media) induced PF-derived steady-state MCP-1 mRNA expression that was markedly attenuated by the presence of neutralizing TNF and IL-1 beta antibodies. Furthermore, we showed the dose- and time-dependent suppression of IL-1 beta-stimulated PF-derived MCP-1 by dexamethasone and prostaglandin E2. These findings demonstrated that PF are an important cellular source of MCP-1 and this production of MCP-1 may be influenced by immunomodulators.

Antibodies↗
PubMed1992

Tumor emboli from lung neoplasms involving the pulmonary vein.

Systemic tumor embolization during pulmonary resection for lung neoplasms is an uncommon but potentially catastrophic complication. In recent months, two patients undergoing pulmonary resection for bronchogenic carcinoma were found at operation to have tumor extending into a pulmonary vein. Both patients had systemic tumor embolization, one with a fatal outcome because of occlusion of the superior mesenteric artery. The possibility of systemic tumor embolization should be considered in patients with large, central tumors and particularly those that abut the pulmonary veins. The implications of such pulmonary vein involvement is reviewed, and an algorithm for postoperative evaluation and management of these patients is presented.

Aged↗
PubMed1990

Descending necrotizing mediastinitis: transcervical drainage is not enough.

One of the most lethal forms of mediastinitis is descending necrotizing mediastinitis, in which infection arising from the oropharynx spreads to the mediastinum. Two recently treated patients are reported, and the English-language literature on this disease is reviewed from 1960 to the present. Despite the development of computed tomographic scanning to aid in the early diagnosis of mediastinitis, the mortality for descending necrotizing mediastinitis has not changed over the past 30 years, in large part because of continued dependence on transcervical mediastinal drainage. Although transcervical drainage is usually effective in the treatment of acute mediastinitis due to a cervical esophageal perforation, this approach in the patient with descending necrotizing mediastinitis fails to provide adequate drainage and predisposes to sepsis and a poor outcome. In addition to cervical drainage, aggressive, early mediastinal exploration--debridement and drainage through a subxiphoid incision or thoracotomy--is advocated to salvage the patient with descending necrotizing mediastinitis.

Adult↗
PubMed1990

Chemotherapy and radiation therapy before transhiatal esophagectomy for esophageal carcinoma.

Recent efforts to improve survival in patients with esophageal carcinoma have combined both systemic and local therapy. From October 1985 to October 1987, 43 patients with local-regional esophageal cancer (adenocarcinoma in 21, squamous cell in 22) were treated with cisplatin, vinblastine, and 5-fluorouracil chemotherapy concurrent with 4,500 cGy radiation therapy for 21 days before transhiatal esophagectomy 3 weeks later. Two patients died of chemotherapy/radiation therapy toxicity. Forty-one completed preoperative chemotherapy/radiation therapy. At operation, 2 patients had incurable metastatic disease; 39 underwent transhiatal esophagectomy. Eleven patients had no residual tumor in the resected specimen for a 27% (11 of 41) pathological complete response rate. Preoperative chemotherapy/radiation therapy resulted in no increased perioperative morbidity as compared with our historical controls. One patient died postoperatively of an unrecognized brain metastasis (2% operative morbidity). At a median follow-up of 27 months, 20 patients (47%) are alive and clinically disease-free and 21 have died, 19 from progression of their carcinoma. The median survival time for all 43 patients is 29 months (Kaplan-Meier estimate), and cumulative survival is 72% at 12 months, 60% at 24 months, and 46% at 36 months. All 11 patients with a complete response are alive at a median follow-up of 36 months, and all are disease-free. The 2-year survival of 60% of this group as compared with 32% in our earlier patients treated with transhiatal esophagectomy alone suggests that intensive combined modality therapy improves survival in these patients. A randomized prospective trial is now in progress.

Adenocarcinoma↗
PubMed1990

Esophagectomy for esophageal disruption.

When esophageal disruption occurs in the presence of preexisting esophageal disease or is associated with sepsis or fluid and electrolyte imbalance, aggressive and definitive therapy often provides the only chance for patient salvage. Twenty-four adults (average age, 59 years) with intrathoracic esophageal perforations underwent esophagectomy: 15, transhiatal esophagectomy without thoracotomy; and 9, transthoracic esophagectomy. Restoration of alimentary continuity with an immediate cervical esophagogastric anastomosis was carried out in 13 patients. Eleven underwent a cervical or anterior thoracic esophagostomy, and 10 of them had a subsequent colonic (7) or gastric (3) interposition from 4 to 32 weeks (average time, 8.6 weeks) later. The perforations were due to esophageal instrumentation (9 patients), acute caustic ingestion (2), emesis (2), intrathoracic esophagogastric anastomotic disruption (2), and other causes (9). Preexisting esophageal disease in 20 patients included chronic strictures (10 patients), reflux esophagitis (3), esophageal cancer (3), achalasia (2), diffuse spasm (2), and monilial esophagitis (1 patient). Ten patients were operated on within 12 hours after the injury; 3, within 12 to 24 hours; and 11, within three to 45 days (average interval, 6.6 days). There were three hospital deaths (13%). Nineteen of the 21 survivors were able to swallow comfortably until the time of death or latest follow-up. Aggressive diagnosis and aggressive treatment of life-threatening esophageal perforations are advocated. Conservative procedures (repair, diversion, or drainage) for a perforation with preexisting esophageal disease often inflict more morbidity than esophageal resection, which eliminates the perforation, the source of sepsis, and the underlying esophageal disease. The decision to restore alimentary continuity in a single stage must be individualized.

Adult↗
PubMed1990

Concurrent chemotherapy and radiation therapy followed by transhiatal esophagectomy for local-regional cancer of the esophagus.

Forty-three patients with local-regional squamous-cell carcinoma of the esophagus or adenocarcinoma of the esophagus, cardia, or gastroesophageal junction were treated with concurrent cisplatin, vinblastine, fluorouracil (5-FU), and radiation therapy (RT) over 21 days. A transhiatal esophagectomy (THE) was planned on day 42. Seventy-nine percent had T2 primaries by clinical staging and 56% had enlarged regional nodes (N) on computed tomographic (CT) scan. Forty-one patients completed the preoperative treatment and went to surgery (95% operability rate), and 36 (84%) were completely resected. Ten of the 41 operative candidates had no evidence of tumor in the resected esophagus and nodal tissue (tumor0 node0; T0N0), 24% complete response (CR). Myelosuppression was the major toxicity with grade 3 or 4 leukopenia in 93% of patients and two preoperative treatment-related deaths. At a median follow-up of 26 months, the median survival time (MST) of all 43 patients registered on study has not been reached. The MST of the 36 completely resected patients and the 10 complete responders has not been reached; 70% and 100%, respectively, are alive at 24 months. The MST by histology is 21 months for the 22 squamous patients and has not been reached for the 21 adenocarcinoma patients registered on study. In a prognostic factor analysis, clinical N status, histology, and the percent of cisplatin and vinblastine tolerated were significant predictors for survival. These survival results suggest a significant improvement over the 14-month MST observed in our previous trial using preoperative chemotherapy only in a similar patient population, and a 12-month MST in a historic control group undergoing THE. A randomized trial is now in progress to convincingly determine if survival is prolonged by this therapy.

Adenocarcinoma↗
PubMed1989

Continued assessment of the combined Collis-Nissen operation.

The combined Collis-Nissen operation has been performed in 353 patients. Forty-five percent had reflux esophagitis without stricture; 20%, peptic stricture; 72%, a sliding hiatal hernia; 17%, a paraesophageal hernia; 21%, previous antireflux operation; 15%, esophageal spasm; 8%, scleroderma; and 32%, marked obesity. There were 4 postoperative deaths (mortality rate, 1.1%). Complications occurred in 28 patients (8%) and included wound infection (2.2%), esophageal or gastroplasty tube leak (1.7%), bleeding (1.1%), splenic injury, gastric atony, and crural repair dehiscence (each less than 1%). Follow-up includes personal interview, esophageal manometry, and standard acid reflux testing. The average length of follow-up for 261 patients (74%) followed at least 12 months is 43.8 months. Fifty-eight percent have been followed at least 36 months; 41%, 48 months; and 29%, 60 months or longer. Subjectively, in these 261 patients, reflux has been eliminated in 75%, is mild in 11%, is moderate in 9%, and is severe in 5%. Eight percent have postthoracotomy pain; 3%, early satiety ("bloats"); and 1%, postvagotomy diarrhea. Seventeen percent require either periodic or regular esophageal dilations for dysphagia. Objectively, intraesophageal pH studies show good reflux control in 91% and poor reflux control in 9%. Twenty-six patients (10%) have required reoperation for recurrent reflux or dysphagia. These results substantiate satisfactory reflux control using the Collis-Nissen operation in patients at risk for recurrence after standard repairs, but also emphasize that, like other antireflux procedures, the Collis-Nissen operation is not without some degree of postoperative adverse symptoms.

Adolescent↗
PubMed1989

Esophageal resection for achalasia: indications and results.

Although esophagomyotomy is highly effective as the initial surgical treatment of most patients with achalasia, those with either recurrent symptoms after a previous esophagomyotomy or a megaesophagus do not respond as well to esophagomyotomy. Total thoracic esophagectomy was performed in 26 patients (average age, 49 years) with achalasia. Eighteen had a history of a previous esophagomyotomy, and 18 had a megaesophagus (esophageal diameter of 8 cm or larger). In 24 patients, a transhiatal esophagectomy without thoracotomy was the operative approach; 2 patients required a transthoracic esophagectomy because of intrathoracic adhesions from prior operations. The stomach was used as the esophageal substitute in all patients; it was positioned in the posterior mediastinum, and a cervical anastomosis was performed. Intraoperative blood loss averaged 765 mL. Major postoperative complications included mediastinal bleeding requiring thoracotomy (2), chylothorax (2), and anastomotic leak (1). There were no postoperative deaths. The average postoperative hospital stay was ten days. Follow-up is complete and ranges from 3 to 91 months (average duration, 30 months). All but 1 patient with severe psychiatric disease eat a regular, unrestricted diet without postprandial regurgitation. Early postoperative anastomotic dilation was required in 10 patients. Dumping syndrome has occurred in 5 patients. It is concluded that esophagectomy provides the most reliable treatment of esophageal obstruction, pulmonary complications, and potential late development of carcinoma in the patient with a megaesophagus of achalasia or a failed prior esophagomyotomy and that it is a far better option in these patients than esophagomyotomy, cardioplasty procedures, or limited esophageal resection.

Adolescent↗
PubMed1988

The combined Collis-Nissen operation for esophageal reflux strictures.

This report evaluates the efficacy of the combined Collis-Nissen operation in achieving long-term reflux control in patients with reflux strictures. A Collis-Nissen procedure with dilation of a reflux stricture was performed in 64 adults. The strictures were mild (easily dilated) in 37, moderate (requiring some force to dilate) in 17, and severe (requiring very forceful dilation) in 10. Two strictures were perforated intraoperatively. There was 1 postoperative death, and 4 patients have been lost to follow-up. The remaining 59 patients have been followed from 2 to 120 months (average, 43 months) after operation. Subjectively, reflux is absent in 48 (81%), mild in 4 (7%), moderate in 5 (9%), and severe in 2 (3%). Objectively, intraesophageal pH studies show good or excellent reflux control in 94% at 1 year and 66% at 2 to 5 years. Dysphagia has been eliminated in 71%, is mild in 10%, moderate (requiring occasional dilation) in 12%, and severe (requiring regular dilations) in 7%. The combined Collis-Nissen operation provides good long-term reflux control and relief of dysphagia in most patients with reflux strictures. However, patients with reflux strictures after previous repairs are likely to have unsatisfactory results and may best be managed with resectional therapy. Resection may also ultimately prove to be a better option for patients with more severe strictures.

Anastomosis, Surgical↗
PubMed1988

Bronchogenic carcinoma metastatic to normal-sized lymph nodes: frequency and significance.

CT staging of mediastinal lymph node metastases from bronchogenic carcinoma is a subject of considerable controversy. The frequency of metastases to normal-sized lymph nodes is a critical issue related to the sensitivity of CT. The authors prospectively examined 42 patients with bronchogenic carcinoma with CT; in 39, careful surgical-pathologic correlation of mediastinal lymph node status was possible. Only 7% had metastases limited to mediastinal lymph nodes that were normal-sized at CT. This reflected a low overall frequency of metastases to normal-sized nodes and several diagnostic factors that converted potentially false-negative studies into true-positive CT studies. In this small series, metastases to enlarged nodes were more likely to have extracapsular spread of tumor, a poor prognostic factor. Overall, the authors do not consider metastases to normal-sized mediastinal lymph nodes to be a major problem in CT staging of non-small cell lung cancer.

Adenocarcinoma↗
PubMed1988

Mediastinal lymph nodes: relaxation time/pathologic correlation and implications in staging of lung cancer with MR imaging.

The authors measured the T1 and T2 relaxation times of freshly excised human mediastinal lymph nodes to determine whether the times are clinically useful in distinguishing benign from malignant nodes. All measurements were performed at 20 MHz and 40 degrees C, within 45 minutes of lymph node excision. Mean T1 and T2 relaxation times of 99 benign nodes were 566 msec (standard deviation [SD], 117 msec) and 92 msec (SD, 29 msec), respectively. For the 16 malignant nodes, these times were 640 msec (SD, 138 msec) and 105 msec (SD, 26 msec), respectively (P less than .05 for difference in T1 times, P greater than .05 for difference in T2 times). Histograms showed considerable overlap in the relaxation times of benign and malignant nodes such that absolute measurement of these times will likely be of limited clinical value.

Humans↗
PubMed1988

Radiologic evaluation of the subcarinal lymph nodes: a comparative study.

Subcarinal lymph nodes are commonly involved by metastases from cancers of both the right and left lungs. No data exist on the relative accuracy of radiologic methods for evaluating subcarinal nodes. We prospectively studied lung cancer patients who were surgical candidates with CT, MR imaging (0.35 T), esophagography, and anteroposterior tomography. Forty-six patients who subsequently underwent thoracotomy had excision or sampling of subcarinal nodes at mediastinoscopy. All 46 had CT scans, 27 had MR imaging, 23 had esophagography, and 21 had anteroposterior tomography. Receiver-operating characteristic curves were constructed for each technique, and the area under each curve was calculated. MR and CT were nearly identical in subcarinal evaluation, with areas under the receiver-operating characteristic curves of 0.90 and 0.86, respectively; both were superior to esophagography (0.55) and anteroposterior tomography (0.61). The size threshold at which subcarinal nodes were considered abnormally enlarged in this lung cancer population was 11 mm in short axis for CT, agreeing with the size threshold previously reported for a normal population. The size threshold for abnormal nodal enlargement with MR imaging was 18 mm in short axis. We conclude that CT and MR imaging are comparable in the detection of subcarinal lymphadenopathy and are superior to both tomography and esophagography. Different size thresholds for metastatic subcarinal nodes are needed for CT and MR imaging to be comparable in overall performance.

Carcinoma, Non-Small-Cell Lung↗