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Biomedical subjects

M B Orringer

Publications and source records attributed to M B Orringer.

At least 19 recordsLinked to original sources

Concurrent preoperative chemotherapy and radiation therapy in localized esophageal adenocarcinoma.

Twenty-four patients with localized, potentially resectable adenocarcinoma of the esophagus were enrolled in this study to evaluate the use of preoperative chemotherapy and radiation therapy, followed by transhiatal esophagectomy. The patients were newly diagnosed and had received no prior treatment. Radiation therapy consisted of 4900 cGy, administered as 350-cGy fractions 5 days a week for 14 fractions. The chemotherapy consisted of 5-fluorouracil 300 mg/m2/day administered as a continuous 24-hour intravenous infusion for 96 hours each week, concomitantly with the radiation therapy. After a 3-week rest, patients underwent transhiatal esophagectomy. Twenty-two patients could be observed for their responses to the chemotherapy and radiation regimen. Radiographically, 41% showed improvement, 36% had stable disease, and 23% had progression. Nineteen patients underwent surgery; all patients had total gross removal of disease, and two patients had a complete histologic response. All 24 patients could be examined for toxicity assessment. There were three deaths during the treatment period: one patient died of a perioperative complication, one of pneumonia, and one of a myocardial infarction. Eleven patients eventually had pleural and/or pericardial effusions, and six of these were symptomatic. All 24 patients could be examined for survival analysis. The median follow-up for all patients was 12.5 months, with 32.5 months for all surviving patients. Median survival was reached at 11 months. Disease-free survival was 9.5 months. It was concluded that the radiation-fractionation schedule in this preoperative regimen was associated with marked toxicity in the form of pleural and pericardial effusions. There was no improvement in survival compared with historic controls. The role of combined preoperative treatment in this patient population has yet to be determined.

Adenocarcinoma

Adjuvant treatment using transfer factor for bronchogenic carcinoma: long-term follow-up.

Transfer factor, a dialyzable lymphocyte extract that may act as an immune stimulator by transferring antigen-specific immunity between genetically dissimilar individuals, was administered in a prospective, randomized study to patients with non-small cell bronchogenic carcinoma. Between 1976 and 1982, 63 patients who underwent pulmonary resection, mediastinal lymph node dissection, and, when indicated by the presence of mediastinal lymph node involvement, mediastinal irradiation were randomized into two groups. Group 1 (n = 28) received 1 mL of pooled transfer factor at 3-month intervals after operation; group 2 (n = 35 ) served as controls and received saline solution. There were no statistically significant differences between the two groups with respect to age, sex, tumor histology, stage of disease, or extent of resection. One patient was lost to follow-up at 96 months; follow-up was complete in all others through July 1990. In patients receiving transfer factor, the 2-, 5-, and 10-year survival rates were 82%, 64%, and 43% respectively, whereas in controls they were 63%, 43%, and 23%. Survival in patients receiving transfer factor was consistently better than in those receiving placebo. Furthermore, survival in patients receiving transfer factor was greater at all stages of disease for both adenocarcinoma and squamous cell carcinoma. Although these long-term results were not statistically significant using survival analysis with covariates (p = 0.08), they confirm our previously reported short-term findings suggesting that administration of transfer factor, either through nonspecific immune stimulation, enhancement of cell-mediated immunity, or an as yet undefined mechanism, can improve survival in patients with bronchogenic carcinoma.

Adenocarcinoma

Anterior mediastinal tracheostomy with and without cervical exenteration.

Anterior mediastinal tracheostomy (AMT) facilitates resection of stomal recurrences after laryngectomy for carcinoma and tumors involving the cervicothoracic trachea and esophagus. Erosion of the innominate artery has been reported as a frequent major complication of AMT, and routine prophylactic division of the innominate artery with AMT has even been advised. Forty-four patients underwent AMT, 10 as an isolated procedure (for stomal recurrence [5], laryngeal carcinoma [1], or benign stenosis after laryngectomy [4]) and 34 with concomitant cervical exenteration (laryngopharyngoesophagectomy) for laryngeal, thyroid, or cervicothoracic esophageal malignancies. Transposition of the remaining tracheal stump beneath and to the right of the innominate artery to eliminate tension on the vessel was carried out in 14 patients (32%). Postoperatively, anastomotic leaks complicated nine of 31 pharyngogastric anastomoses. Iatrogenic hypoparathyroidism occurred in 10 patients. All six hospital deaths (14%) occurred in patients undergoing AMT with cervical exenteration, not isolated AMT. There was only one instance of innominate artery erosion. Survival was related to the pathology for which AMT was performed. Anterior mediastinal tracheostomy is a valuable adjunct in the treatment of select patients with malignancies of the cervicothoracic trachea and esophagus, and with attention to operative detail, innominate artery erosion should rarely, if ever, complicate the operation. Prophylactic division of the innominate artery with AMT is unnecessary.

Adult

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

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

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

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

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

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

Monilial esophagitis: an increasingly frequent cause of esophageal stenosis?

Acute monilial esophagitis generally responds well to oral nystatin therapy, and long-term sequelae of this condition have not been well recognized. Nor is it generally appreciated that Candida infections of the esophagus may occur in subacute or chronic form. Four men, 34, 40, 41, and 49 years old, have been treated for esophageal stenoses resulting from different types of chronic monilial esophageal involvement. All were seen with painless dysphagia and strictures of the upper half of the thoracic esophagus. In 2 patients, an associated roentgenographic pattern of "intramural esophageal pseudodiverticulosis" was present. Two patients have been treated successfully with esophageal dilation, 1 required substernal colonic bypass of the stenotic, perforated esophagus, and 1 is being evaluated for esophageal bypass. Esophageal moniliasis must be considered in the differential diagnosis of benign esophageal strictures, particularly those involving the upper half of the thoracic esophagus.

Adult

Combined Collis-Nissen reconstruction of the esophagogastric junction.

Recent reports have indicated that combined Collis-Belsey reconstruction of the esophagogastric junction fails to control reflux in 30 to 46% of patients undergoing the procedure. The major factor thought to be responsible for this result is the limited Belsey fundoplication possible after construction of the gastroplasty tube. This report describes our technique of combining the Collis gastroplasty with a 360-degree Nissen type fundoplication. The radiographic and manometric characteristics of the distal esophageal high-pressure zone produced by the Collis-Nissen operation are discussed.

Adult