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Biomedical subjects

M B Orringer

Publications and source records attributed to M B Orringer.

At least 73 records · Page 4Linked to original sources
PubMed1994

Tube jejunostomy as an adjunct to esophagectomy.

BACKGROUND: The safety and efficacy of various methods of accessing the intestinal tract, including needle catheter jejunostomy, have been well described. This review represents an evaluation of the Witzel tube jejunostomy as an adjunct to esophagectomy. METHODS: The records of 523 patients who underwent esophagectomy for benign or malignant disease from 1976 to 1991 were reviewed. Each patient underwent placement of a tube jejunostomy at the time of esophagectomy and esophageal reconstruction. Utilization of the jejunostomy tube and the complications related to its placement were examined. RESULTS: The feeding jejunostomy was used in all patients in the initial postoperative period, for more than 3 weeks in 11%, and for more than 2 months in 6.9%. Major complications related to the jejunostomy tube occurred in 11 patients (2.1%). There were no fatal complications. CONCLUSIONS: Tube jejunostomy is a useful adjunct to esophagectomy for providing enteral nutrition during the postoperative period. The Witzel jejunostomy as described herein is comparable in terms of safety, function, and complication rate to the needle catheter jejunostomy and has certain technical advantages. Routine use of tube jejunostomy is recommended in patients undergoing esophagectomy.

Adolescent↗
PubMed1993

Macrophage inflammatory protein-1 alpha expression in interstitial lung disease.

Mononuclear phagocyte (M phi) recruitment and activation is a hallmark of a number of chronic inflammatory diseases of the lung, including sarcoidosis and idiopathic pulmonary fibrosis (IPF). We hypothesized that macrophage inflammatory protein-1 (MIP-1 alpha), a peptide with leukocyte activating and chemotactic properties, may play an important role in mediating many of the cellular changes that occur in sarcoidosis and IPF. In initial experiments, we demonstrated that human rMIP-1 alpha exerted chemotactic activities toward both polymorphonuclear leukocytes and monocytes, and these activities were inhibited by treatment with rabbit anti-human MIP-1 alpha antiserum. In support of the potential role of MIP-1 alpha in interstitial lung disease, we detected MIP-1 alpha in the bronchoalveolar lavage fluid of 22/23 patients with sarcoidosis (mean 443 +/- 76 pg/ml) and 9/9 patients with IPF (mean 427 +/- 81 pg/ml), whereas detectable MIP-1 alpha was found in only 1/7 healthy subjects (mean 64 +/- 64 pg/ml). In addition, we found a 2.5- and 1.8-fold increase in monocyte chemotactic activity in BALF obtained from patients with sarcoidosis and IPF respectively, as compared to healthy subjects, and this monocyte chemotactic activity, but not neutrophil chemotactic activity, was reduced by approximately 22% when bronchoalveolar lavage fluid from sarcoidosis and IPF patients were preincubated with rabbit antihuman MIP-1 alpha antibodies. To determine the cellular source(s) of MIP-1 alpha within the lung, we performed immunohistochemical analysis of bronchoalveolar lavage cell pellets, transbronchial biopsies, and open lung biopsies obtained from patients with IPF and sarcoidosis. Substantial expression of cell-associated MIP-1 alpha was detected in M phi, including both alveolar AM phi and interstitial M phi. In addition, interstitial fibroblasts within biopsies obtained from sarcoid and IPF patients also expressed immunoreactive MIP-1 alpha. Minimal to no detectable MIP-1 alpha was expressed in alveolar M phi from healthy subjects or interstitial cells in lung biopsy specimens obtained from patients undergoing thoracotomy for malignancy. Furthermore, pulmonary fibroblasts isolated from patients with IPF produced greater amounts of MIP-1 alpha after challenge with IL-1 beta than did similarly treated pulmonary fibroblasts recovered from patients without fibrotic lung disease. Our findings suggest that MIP-1 alpha is expressed in increased amounts within the airspace and interstitium of patients with sarcoidosis and IPF, and that this cytokine may be an important mediator of both M phi activation and recruitment that characterize these disease states.

Adult↗
PubMed1993

Amplification and over-expression of the EGFR and erbB-2 genes in human esophageal adenocarcinomas.

Esophageal cancer is one of the 10 most prevalent human cancers worldwide. The incidence of esophageal adenocarcinoma is on the rise and patients with this disease typically have very poor prognosis. Informative biomarkers would benefit the clinical management of this disease. We examined 13 cases with esophageal adenocarcinomas and 5 cases with Barrett's esophagus for amplification of the EGFR and erbB-2 genes. We detected multiple copies of the EGFR gene in 30.8% of the tumors and multiple copies of the erbB-2 gene in 15.4% of the tumors. Of the cases with amplification of the erbB-2 gene, co-amplification of the EGFR gene was found. Multiple copies of the EGFR gene were also found in one case of Barrett's esophagus. Immunohistochemical staining of the tissues revealed increased expression of the erbB-2 protein in Barrett's mucosa and adenocarcinoma, but no associations between staining intensity and degree of EGFR or erbB-2 gene amplification, histology, or tumor stage were found. Differential polymerase chain reaction was examined as a method for pre-operative detection of gene amplification in esophageal tumors and Barrett's mucosa.

Adenocarcinoma↗
PubMed1993

Systematic survey of opinion regarding the thoracic surgery residency.

To summarize this rather wide-ranging study, let us review the high points. The future practice of thoracic surgery will be increasingly affected by governmental factors and will have even greater technological dimensions. To do this work, we must continue to attract high-caliber individuals, and this is best accomplished by the early and continuing involvement in the educational process of strong role models from our field. These future surgeons must be motivated to do good work and should have high ethical standards as well as maturity and high intelligence. Experienced, involved faculty leading the residents through a broad program that offers graduated assumption of clinical and leadership responsibilities will facilitate the development of mature clinical judgment. Residents must be taught the clinical skills necessary to do all thoracic operations, leaving subspecialization to postresidency fellowships. The educational program should be humane in its demands and collegial in its application. It should incorporate experiences beyond the operating room, including the opportunity to read, think, and interact with local mentors and colleagues from around the country. The requirements of certification should not be so rigid as to preclude the development of different pathways to the same end. Likewise, although the accreditation process must protect the resident from exploitation, it must not be so restrictive that it does not allow for educational innovation and justifiable differences among programs. These are the thoughtful opinions of our colleagues. They deserve serious consideration.

Accreditation↗
PubMed1993

Sucrase-isomaltase gene expression in Barrett's esophagus and adenocarcinoma.

BACKGROUND: Specialized Barrett's esophageal mucosa, characterized by incomplete intestinal metaplasia of the esophageal mucosa, is associated with the development of adenocarcinoma. Although the intestinal disaccharidase sucrase-isomaltase (SI) has been shown in incomplete intestinal metaplasia of the stomach, it is commonly believed that Barrett's mucosa does not express SI based on the lack of enzymatic activity. This study was undertaken to determine whether the SI gene is expressed in Barrett's epithelium and its associated adenocarcinoma at the level of messenger RNA (mRNA) and protein. METHODS: Reverse transcription polymerase chain reaction was used to determine the presence of SI mRNA in Barrett's esophagus and esophageal adenocarcinomas. Cellular localization of SI protein was determined by immunohistochemistry. RESULTS: SI mRNA was identified in 76% of Barrett's epithelium and 82% of esophageal adenocarcinomas. The transcriptional initiation site for SI in these tissues was identical to that of the small intestine. Immunohistochemical localization showed that SI was directed to the apical membrane in Barrett's epithelium in contrast to a more diffuse cytoplasmic pattern in esophageal adenocarcinomas. CONCLUSIONS: Columnar cells of specialized Barrett's epithelium express SI and are, therefore, phenotypically similar to those in incomplete intestinal metaplasia of the stomach with respect to intestinal gene expression.

Adenocarcinoma↗
PubMed1993

Recurrent esophageal carcinoma: CT evaluation after esophagectomy.

PURPOSE: Computed tomographic (CT) scans were retrospectively reviewed for evidence of (a) intragastric soft-tissue mass or gastric wall thickening, (b) extragastric soft-tissue mass or mediastinal lymph node enlargement (local-regional disease), (c) abdominal lymph node enlargement, and (d) metastatic disease to distant organs. MATERIALS AND METHODS: Fifty-eight patients with a clinical suspicion of recurrent esophageal carcinoma underwent CT. The thoracic level of local-regional recurrence was compared with the level of the primary tumor. RESULTS: Proof of recurrence status was obtained in 52 of 58 patients. Of the 58 patients, 36 (62%) had CT findings of recurrence, 16 (28%) had no CT findings of recurrence, and six (10%) had CT findings questionable for recurrence. CT accuracy for determining recurrence status was 87%. There was no correlation between the level of primary tumor and that of recurrence. CONCLUSION: At CT, tumor recurrences were most commonly seen as some combination of local-regional disease, distant metastases, and abdominal lymph node enlargement. CT findings isolated to one region were seen only occasionally.

Adenocarcinoma↗
PubMed1993

Preoperative chemoradiation followed by transhiatal esophagectomy for carcinoma of the esophagus: final report.

PURPOSE: In 1990 we published the results of an intensive 3-week preoperative chemoradiation regimen for locoregional esophageal cancer that suggested improved survival compared with historical controls. We now report the long-term results at a median follow-up of 78.7 months. PATIENTS AND METHODS: Forty-three patients with locoregional squamous cell carcinoma or adenocarcinoma of the esophagus or cardia were treated with fluorouracil (5-FU), cisplatin, and bolus vinblastine concurrent with radiation administered over 21 days. Transhiatal esophagectomy was performed on day 42. RESULTS: Forty-one patients (95%) completed the preoperative treatment, and 36 (84%) had a potentially curative resection. Ten of 41 (24%) had no tumor in the resected esophagus and nodal tissues (path-negative group). The median survival duration of all 43 patients registered on study was 29 months; 34% were alive at 5 years. By histology, median survival durations were 32 months for 21 adenocarcinoma patients and 23 months for 22 squamous cell patients, with corresponding 5-year survival rates of 34% and 31%, respectively. Analysis of the 36 patients who underwent a potentially curative resection demonstrated median survival durations of 32 and 44 months and 5-year survival rates of 36% and 43%, respectively, for adenocarcinoma and squamous cell histologies. Path-negative (complete response [CR]) patients had a median survival duration of 70 months and 60% were alive at 5 years, while those patients with residual tumor in the resected esophagus had a median survival duration of 26 months and 32% were alive at 5 years (P = .114 by the log-rank test and P = .04 by the Wilcoxon test). CONCLUSION: The results of this regimen appear improved over those reported with surgery alone, with an approximate doubling of the 5-year survival rate. Thirty-two percent of patients with residual tumor in the esophageal specimen are long-term survivors, which suggests a benefit from esophagectomy. A randomized trial is in progress to compare this preoperative regimen with immediate surgery.

Adenocarcinoma↗
PubMed1993

Diagnosis of unilateral mainstem bronchial obstruction following single-lung transplantation with routine spirometry.

Single-lung transplantation has become a treatment option for many patients with advanced pulmonary disease. Recent advances in surgical technique and refined immunosuppressive regimens have led to improvement in long-term outcomes, but postoperative complications, including airway disorders, remain problematic. Serial spirometry with flow-volume loops is sensitive in detecting early small-airway disease associated with lung allograft rejection or bronchiolitis obliterans, but its role in the diagnosis of large-airway disease in the posttransplantation setting has not been delineated. In this report, we describe a novel alteration in the configuration of the flow-volume loop in a patient who developed unilateral mainstem bronchial obstruction following single-lung transplantation for severe emphysema. Surveillance spirometry performed 6 weeks after transplantation demonstrated a new initial plateau in the maximal expiratory flow-volume curve suggestive of a variable intrathoracic airway obstruction. This unique aberration in the flow-volume curve sheds new insight into the physiologic abnormalities of spirometry in patients receiving lung transplants.

Acute Disease↗
PubMed1993

Multimodality therapy for esophageal carcinoma--update.

Transhiatal esophagectomy with mobilization of the stomach to replace the esophagus has been used to provide palliation of dysphagia at the University of Michigan for more than 15 years. The subtotal esophageal resection is believed to be preferable to the transthoracic approach that has been considered the standard for this surgery. As experience with the technique has increased, complications have decreased. Most patients are discharged, able to swallow, by the 10th or 11th postoperative day. Survival in these patients is no worse than that reported after more traditional transthoracic esophagectomy, and the transhiatal route has reduced postoperative pulmonary complications and the incidence of mediastinitis from anastomotic leak, which is fatal in 50% of patients. In a phase II trial of preoperative combined radiation therapy and chemotherapy with cisplatin, vinblastine, and continuous-infusion 5-fluorouracil in 45 patients, survival after esophagectomy seemed considerably better than in our historical control subjects treated with transhiatal esophagectomy alone. The 3-year survival of the 43 patients was 46% compared with 23% of those who received only surgery. Considering only the 27% of those patients who had no cancer in their resected specimens, ie, the complete responders, the 5-year survival is 70%. A phase III trial is now accruing patients in an attempt to confirm these results.

Anastomosis, Surgical↗
PubMed1993

The production of interleukin-1 receptor antagonist by human bronchogenic carcinoma.

Bronchogenic carcinoma displays an aggressive clinical course that may reflect a capacity to evade host defenses. We postulated that tumors may elaborate interleukin-1 receptor antagonist protein (IRAP) to escape host interleukin-1-dependent responses. Homogenates of human bronchogenic lung tumors demonstrated significant increases of IRAP compared with normal lung tissue controls (n = 48). There was no significant difference in interleukin-1 beta levels between tumor and normal lung tissue. Immunohistochemical staining localized IRAP to tumor cells. Semiquantitative pathological analysis demonstrated a modest inflammatory cell infiltrate with qualitative differences between tumors of different histology. Western blot analysis of tumor homogenates demonstrated several molecular weight forms of IRAP. Finally, antigenic IRAP was detected in supernatants of the human bronchogenic carcinoma cell line (A549) maintained in vitro. These findings illustrate the capacity of bronchogenic tumors to produce and secrete IRAP that may be important in tumor evasion of host defenses.

Adenocarcinoma↗
PubMed1993

Transhiatal esophagectomy for benign and malignant disease.

Transhiatal esophagectomy has been performed in 583 patients with diseases of the intrathoracic esophagus: 166 (28%) benign and 417 (72%) malignant (6% upper, 28% middle, and 66% lower third and cardia). The benign esophageal diseases included strictures (40%); neuromotor dysfunction-achalasia (24%), esophageal spasm (8%); recurrent gastroesophageal reflux (16%); acute perforation (5%); acute caustic injury (2%); and others (3%). Among the patients with benign disease, 60% had undergone at least one prior esophageal operation. Transhiatal esophagectomy was possible in 97% of patients in whom it was attempted, 19 patients (13 with benign disease and 6 with carcinoma) requiring addition of a thoracotomy for esophageal resection. Esophageal resection and reconstruction were performed in a single operation in all but 5 patients. The esophageal substitute was positioned in the posterior mediastinum in the original esophageal bed in 96%. Stomach was used to replace the esophagus in 553 patients (95%) and colon in 28 (5%) who had undergone prior gastric resections. Overall hospital mortality was 5% in patients with benign disease and 5% in those with carcinoma. There was 1 intraoperative death caused by uncontrollable hemorrhage. Complications included intraoperative entry into a pleural cavity necessitating a chest tube (74%), anastomotic leak (9%), recurrent laryngeal nerve paralysis (3%), and chylothorax and tracheal laceration (< 1% each). Three patients required reoperation for mediastinal bleeding. Average intraoperative blood loss was 875 ml (1023 ml for benign disease and 817 ml for carcinoma). Of the surviving patients, 88% were discharged able to swallow within 3 weeks of operation and 78% within 2 weeks. The actuarial survival of the patients with carcinoma is similar to that reported after more traditional transthoracic esophagectomy. Among patients with benign disease, good or excellent functional results have been achieved in nearly 70% after a cervical esophagogastric anastomosis. Although approximately 44% have required one or more anastomotic dilations within 1 to 3 months of operation, true anastomotic strictures have developed in 10%. Clinically troublesome nocturnal reflux has occurred in 3%. Transhiatal esophagectomy is feasible in most patients requiring esophageal resection for either benign or malignant disease and is a safe, well-tolerated operation if performed with care and for the proper indications.

Adenocarcinoma↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗