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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. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5

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. Images Figure 1 Figure 2

Genomic DNA amplification in tumors is frequently associated with an increased gene copy number of oncogenes or other cancer-related genes. We have used a two-dimensional whole-genome scanning technique to identify gene amplification events in esophageal adenocarcinomas. A multicopy genomic fragment from a tumor two-dimensional gel was cloned, and genomic amplification encompassing this fragment was confirmed by Southern blot analysis. The corresponding DNA sequence was matched by BLAST to a BAC contig, which allowed the use of electronic-PCR to localize this amplicon to 19q12. Sequence tagged site-amplification mapping, an approach recently implemented in our laboratory (Lin, L. et al., Cancer Res., 60: 1341-1347,2000), was used to characterize the amplicon. Genomic DNA from 65 esophageal and 11 gastric cardia adenocarcinomas were investigated for 19q12 amplification using quantitative PCR at 11 sequence tagged site markers neighboring the cloned fragment. The amplicon was narrowed from8 cM to a minimal critical region spanning0.8 cM, between D19S919 and D19S882. This region includes the cyclin E gene. Fourteen expressed sequence tags (ESTs) covering the minimal region were then assayed for potential gene overexpression using quantitative reverse transcription-PCR. Seven of the selected ESTs were found to be both amplified and overexpressed. Among these seven ESTs, cyclin E showed the highest frequency of gene amplification and overexpression in the tumors examined, which allowed us to finalize the core-amplified region to300 kb. These results indicate that cyclin E is the likely target gene selected by the amplification event at 19q12. The fact that cyclin E overexpression was found only in the amplified tumors examined indicates that gene amplification underlies the cyclin E gene overexpression. Our study represents the first extensive analysis of the 19q12 amplicon, and is the first to physically map the core-amplified domain to a region of300 kb that includes cyclin E. Amplification of 19q12 was found neither in the 28 esophageal squamous cancers nor in the 39 lung adenocarcinomas examined but was observed in 13.8% of esophageal and 9.1% of gastric cardia adenocarcinomas.

The incidence of esophageal adenocarcinomas has increased greatly over the past 20 years. The genetic alterations associated with this disease, however, remain largely unknown. We identified recently a novel amplicon at 8p22-23 in esophageal adenocarcinomas using the restriction landmark genomic scanning two-dimensional gel technique. Four known genes within or near this amplicon were initially characterized. The cathepsin B (CTSB) gene was found to be amplified in 13% of esophageal tumors. CTSB was shown previously to be overexpressed without amplification in many other human cancers. An approach termed sequence tagged site-amplification mapping has been implemented in the present study, allowing the 8p22-23 amplicon to be narrowed from 12 cM to a2-cM minimal amplified area located between markers D8S552 and D8S1759. The CTSB gene maps within this region. To identify other cancer-related candidate genes in this region, a positional candidate gene approach was subsequently applied to characterize this minimal critical region. An expressed sequence tag (EST), which was included in the minimal critical region, demonstrated both amplification and overexpression. This EST and the extended sequence from the EST were determined to be a novel sequence in the 3' untranslated region of the human GATA-4 gene. GATA-4, a member of a zinc finger transcription factor family, was confirmed to be amplified and overexpressed in esophageal adenocarcinomas and was localized within0.5 kb from CTSB. Furthermore, amplification of 8p22-23 was detected in one of eight gastric cardia adenocarcinomas but was not observed in either human lung adenocarcinomas (n = 39) or in esophageal squamous cell carcinomas (n = 24). The relatively high frequency of the 8p22-23 amplification in esophageal (13.6%) and gastric cardia (12.5%) adenocarcinomas may indicate a specificity of this amplicon for tumors of gastroesophageal origin.

We used TaqMan PCR to detect quantitative anomalies of tumor markers in both tumor and serum DNA from esophageal cancer patients. We demonstrated the potential of this methodology by detecting erbB-2 amplifications in a plurality of esophageal tumor samples. These amplifications were corroborated by Southern blots. We then showed the potential of this methodology to detect quantitative anomalies of erbB-2 in serum DNA from individuals with a corresponding amplification in the tumor. The capability of TaqMan PCR to detect abnormalities in serum of esophageal cancer patients creates an opportunity to diagnose esophageal cancer and to monitor the outcome of treatment with a blood test.

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, laryngeal carcinoma, or benign stenosis after laryngectomy) 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.

This study describes Fas (CD95) expression in Barrett's esophagus, adenocarcinomas of the esophagus, and three esophageal adenocarcinoma cell lines. Immunohistochemical analysis of Barrett's esophagus demonstrated cell surface expression of Fas protein. In contrast, 30.5% of esophageal adenocarcinomas examined by immunohistochemical analysis demonstrated faint cytoplasmic staining, and 69.5% were negative for Fas. Similar levels of Fas mRNA were identified in tumors compared to mRNA levels in esophageal squamous mucosa or Barrett's esophagus. An approximately Mr 48,000 Fas protein was identified by Western blot analysis in tumors that were negative for Fas expression by immunohistochemical analysis. The esophageal adenocarcinoma cell line Seg-1 was negative for Fas expression by immunohistochemical analysis, but Western blot analysis demonstrated abundant, appropriately sized Fas protein. In agreement with the immunohistochemical analysis, flow cytometry of Seg-1 showed minimal amounts of Fas on the cell surface, which correlated with resistance to Fas-mediated apoptosis. No mutations in the Seg-1 Fas coding sequence or exon 1 were identified by sequence analysis. This was confirmed by transient transfection of COS cells with expression vectors generated from the Seg-1 Fas cDNA, which resulted in cell surface expression of the Fas protein. Stable transfection of Seg-1 with a Fas expression vector did not result in efficient Fas expression on the cell surface. Seg-1 cells, transiently transfected with a Fas-FLAG expression vector and examined for protein expression using confocal microscopy and an anti-FLAG antibody, showed that the Fas-FLAG protein was not present on the cell surface but was present in the cytoplasm. Taken together, these results indicate that expression of Fas on the cell surface by esophageal adenocarcinoma is reduced. In an esophageal adenocarcinoma cell line, wild-type Fas protein is retained in the cytoplasm, and this correlates with resistance to Fas-mediated apoptosis. The retention of wild-type Fas protein within the cytoplasm may represent a mechanism by which malignant cells evade Fas-mediated apoptosis.

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.

Helical computed tomography with multiplanar reconstruction (CT/MPR) was used to study proximal airway stenosis.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.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.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.

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.

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.

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.

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.

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.

Transhiatal herniation of colon is uncommon after transhiatal esophagectomy. Two patients with this complication are presented. Presenting symptoms vary depending on the size and contents of the hernia. Patients may be asymptomatic. The diagnosis is suggested by plain chest radiography, and treatment, in symptomatic patients, is surgical reduction of the hernia via a laparotomy.

Between 1965 and 1984, 72 patients underwent operation for adenocarcinoma of the distal esophagus or gastric cardia. A standard transthoracic esophagogastrectomy and esophagogastrostomy was performed in 43 and a transhiatal esophagectomy without thoracotomy and partial proximal gastrectomy was performed in 29. There was no significant difference between the two groups in age, sex, or TNM tumor staging. The perioperative complication rate was 86% in the esophagogastrectomy patients and 48% in the transhiatal esophagectomy patients (p less than 0.05). Mortality was higher in the esophagogastrectomy group (14%) than in the transhiatal esophagectomy group (7%). Average operative blood loss was greater in the esophagogastrectomy patients (2,510 versus 1,187 ml). Average postoperative hospitalization was longer for the esophagogastrectomy patients (22.2 days versus 12.3 days). Both differences are statistically significant (p less than 0.05). Late results, as evaluated by life-table analysis, showed no significant difference in survival between the two groups of patients. Because the morbidity and mortality rates of transhiatal esophagectomy are as low as or lower than those for esophagogastrectomy, late survival is as good, and palliation is superior (less suture-line tumor recurrence and reflux esophagitis), we believe that transhiatal esophagectomy is the preferred operative approach in patients with adenocarcinoma of the distal esophagus or gastric cardia.

Eighty-seven adults have undergone reoperation for recurrent gastroesophageal reflux or complications of prior antireflux procedures. Operations performed included the transthoracic Collis-Nissen procedure (59), Collis-Belsey repair (14), Nissen fundoplication (one), repair of acute postoperative paraesophageal hernia (one), division of obstructing crural suture (one), and esophageal resection (23). Among the 73 patients undergoing an additional hiatal hernia repair, there were two postoperative deaths. Follow-up averages 28 months. Subjectively, results have been excellent or good (no or mild reflux symptoms or dysphagia) in 47 (67%); fair in eight (12%), who have moderate dysphagia or reflux symptoms controlled medically; and poor in 15 (21%), 12 of whom have required additional operations. Early postoperative esophageal dilations were required in 25 patients (36%) and regular dilations in seven (10%). Among the 23 patients undergoing esophageal resection, four had a distal esophagectomy and short-segment colon interposition and 19 had a transhiatal esophagectomy without thoracotomy; stomach was used for esophageal replacement in 14 and colon in five. There were no operative deaths. Follow-up averages 17 months. Thirteen patients have had esophageal dilations (nine early and four regularly), and one has clinically significant reflux. Overall, subjective results are good or excellent in 64 (76%). The results of "redo hiatal hernia operation" are far from ideal. Optimal surgical treatment after the failed antireflux operation requires careful analysis of the existing anatomy and experience to decide when esophageal resection is a safer and more reliable approach than another hiatal hernia repair.

The development at our institution of the radiopharmaceutical 131-I-metaiodobenzylguanidine has permitted for the first time scintigraphic localization of pheochromocytomas. By the use of this scan in combination with contrast-enhanced computed tomography, intrapericardial pheochromocytomas have been demonstrated in eight patients at our hospital during the past 2 years. Four of these patients have been operated upon by us, and each was found to have a pheochromocytoma arising from the heart (left atrium in three and interventricular groove at the aortic root in one). While in one patient it was possible to "shell" the tumor away from the left atrial wall without cardiopulmonary bypass, in the remaining patients, bypass and cardioplegia were required to resect the pheochromocytomas without inducing life-threatening intraoperative hypertension and cardiac arrhythmias. One patient required coronary artery reconstruction and two, excision of the posterior left atrial wall with pericardial replacement. One of these latter two patients died intraoperatively of uncontrollable hemorrhage. The three remaining patients are well and normotensive after more than 1 year of follow-up. Cardiac pheochromocytomas should not be approached as typical posterior mediastinal tumors, or as they are in the abdomen, with the expectation that they will "shell away" from contiguous structures. Cardiopulmonary bypass should be available, and resection of involved myocardium may be necessary for complete removal.

Twenty-four patients underwent combined Collis-Belsey reconstruction of the esophagogastric junction. The primary indication for operation in 19 patients was gastroesophageal reflux. Three patients had achalasia, one diffuse spasm, and one an incarcerated combined sliding and paraesophageal hernia. Postoperatively, symptoms were relieved in all 19 patiients undergoing repair for gastroesophgeal reflux with or without peptic strictures of the esophagus, and barium swallows showed no gastroesophageal reflux. Preoperative average mean and peak pressures in the distal esophageal high pressure zone (HPZ) were 1.38 and 2.72 mm. Hg, respectively; two thirds had no measurable HPZ. Postoperative mean and peak pressures were 6 and 12.36 mm. Hg, respectively; average HPZ length was 2.81 cm. Of 19 patients with massive reflux preoperatively, postoperative acid reflux testing demonstrated no reflux in 14 and minimal to moderate reflux in five. Collis-Belsey reconstruction ot the esophagogastric junction effectively relieves symptoms and controls the complications of gastroesophageal reflux.

Seventy adult patients with thoracic empyema were treated at the University of Michigan Medical Center between 1978 and 1982. Twenty-two (31%) of the empyemas were associated with pneumonia, 23 (33%) occurred as postoperative complications, and seven (10%) were iatrogenic. When used as the initial mode of drainage, repeat thoracentesis was successful in only four of 11 cases (36%). Similarly, closed tube thoracostomy, as initial treatment, was successful in only 14 of 40 cases (35%). Rib resection, however, provided cure or control in 10 of 11 patients (91%) when employed as the first treatment method. Eight of 12 patients (67%) with parapneumonic empyemas were treated successfully with closed tube thoracostomy, in contrast to only two of 17 patients (12%) with postoperative empyemas so treated. Eventual control or cure of empyema was achieved in 57 patients (81%), whereas 13 (19%) died (five from their empyema and eight with empyema as an active problem at the time of death). All of the five empyema-caused deaths occurred in patients who underwent chest tube drainage as the most invasive treatment modality. The mortality rate for immunosuppressed patients was 40% (four of 10 patients). This analysis of a large recent series of adult empyemas suggests that chest tube drainage is often inadequate and more aggressive management is likely to result in fewer treatment failures and fewer total procedures. Early rib resection, especially for postoperative empyemas and those in immunocompromised patients, is recommended.

Eighty-three patients with risk factors predisposing to recurrent reflux after standard hiatal hernia repairs have undergone the Collis-Belsey operation. There were two postoperative deaths. Complications related to multiple operations on the lower esophagus included injury to the spleen (three patients); gastrocutaneous fistula (two patients), and localized ischemic necrosis of esophagus two patients). There were two esophageal perforations. In four of 15 patients, the combination of esophagomyotomy and the Collis-Belsey operation produced functional esophageal obstruction. Three patients have experienced late major lower esophageal bleeding from ulceration of mucosa adjacent to the gastroplasty tube; two the these patients have no demonstrable gastroesophageal reflux. In addition to postoperative interviews and barium swallows, 77 patients have been evaluated with esophageal manometry and acid reflux testing. After an average follow-up of 12 montsh, 19 percent have symptomatic reflux, but 30 percent have moderate-to-severe reflux with pH reflux testing. The recent enthusiasm for the combined Collis-Belsey operation should be tempered by continued, cautious, objective assessment of its long-term results.

Curative resection is impossible in most patients with carcinoma of the esophagus or malignant tracheoesophageal fistulas, because of local tumor invasion or distant metastases. Optimal palliative therapy in these patients should relieve dysphagia and aspiration and restore the ability to swallow comfortably. This report describes a technique for palliation of carcinoma of the esophagus with a substernal gastric bypass after exclusion of the thoracic exophagus with the GIA surgical stapler. The results of this procedure in 10 patients with advanced malignant disease are discussed. Although postoperative morbidity and mortality rates were high, the quality of life achieved with this method of palliation was gratifying. Substernal gastric bypass of the excluded thoracic esophagus is an effective alternative to feeding tubes, prolonged radiation therapy, esophagogastrectomy, or colon bypass in patients with incurable, malignant esophageal disease.

Forty-nine cases of surgically resected adenocarcinomas of the gastric cardia and 23 cases of resected adenocarcinomas arising in Barrett's columnar lined lower esophagus were compared histologically and clinically. Morphologically, the two groups were almost identical in terms of pattern of growth (expansile or infiltrative), degree of differentiation, and extent of spread at the time of operation. These similarities are not surprising, as the two carcinomas arise close to each other from almost identical mucosas. The major histologic difference was the finding of much more frequent dysplasia in the adjacent Barrett's mucosa than in the surrounding cardiac mucosa, probably a reflection of the larger surface area covered by Barrett's than by cardiac mucosa. The groups differed in certain epidemiologic parameters that possibly reflected independent carcinogenetic mechanisms. Thus, although the age ranges and median ages were the same, there was a higher male predisposition among the patients with cardiac carcinoma. In addition, patients with cardiac carcinoma had a significantly higher history of heavy smoking and history of alcohol intake, whereas those with Barrett's carcinoma were much more likely to have hiatal hernias.

Blunt esophagectomy without thoracotomy has been performed in 26 patients: four with benign disease and 22 with carcinomas involving various levels of the esophagus (10 cervicothoracic, one upper third, five middle third, and six distal third). Continuity of the alimentary tract was restored by anastomosing the pharynx or cervical esophagus either to stomach (19 patients) or to a colonic graft (seven patients). Esophageal resection and reconstruction were performed in a single stage in 25 patients, and the esophageal substitute was positioned in the posterior mediastinum in the original esophageal bed in 24 patients. There were no deaths directly related to the technique of blunt esophagectomy. Average intraoperative blood loss was 1,350 ml. for the entire group, 1,650 ml. for those requiring concomitant laryngectomy and 1,050 ml. for those undergoing esophagectomy without laryngectomy. Complications in these patients included pneumothorax (eight), transient hoarseness (five), pleural effusion (five), anastomotic leak (four), subphrenic abscess (one), and cerebrovascular accident (one). The five deaths were due to pheumonia (two), innominate artery rupture (two), and pulmonary embolus (one). Blunt esophagectomy without thoracotomy is safe and is far better tolerated physiologically than the combined transthoracic and abdominal operations more traditionally used for exophageal resection and reconstruction.

Forty adult patients have undergone a 7 to 10 cm cervical esophagomyotomy (from the superior cornu of the thyroid cartilage to behind the clavicle) for cricopharyngeal dysfunction. A Zenker's diverticulum was present in 12 patients (30%) and in five was recurrent. Preoperative symptoms included cervical dysphagia (85%), expectoration of saliva (40%), and intermittent hoarseness (30%). Four patients were being fed through tubes because of total inability to swallow. "Heartburn" was experienced by one half of the patients, but only 12 had acid or food regurgitation. The duration of symptoms ranged from 1 month to 11 years (average 3.9 years). Weight loss had occurred in 15 patients (38%) and ranged from 5.5 to 40.9 kg (average 16 kg). Barium swallows showed no abnormalities in 10 patients. Abnormal findings included a Zenker's diverticulum (12), prominent cricopharyngeal sphincter (11), nasopharyngeal reflux or incoordinated initiation of deglutition, or both (seven), a sliding hiatal hernia (11), and abnormal esophageal motility (seven). Esophageal manometry revealed abnormalities of upper esophageal sphincter (UES) function in only 16 patients. Of 36 patients undergoing standard acid reflux testing, one third had moderate-to-severe gastroesophageal reflux. Seven patients underwent staple resection of a Zenker's diverticulum at the time of cervical esophagomyotomy. Postoperative complications included transient vocal cord paresis (four), vocal cord paralysis (one), and salivary fistula (one). There were no postoperative deaths. After 2 to 48 months (average 16 months) of follow-up, 34 patients (85%) have had a good to excellent result, and six (15%) have not been benefited by operation.

The Blalock-Hanlon procedure has been carried out in 48 neonates with 10 early deaths (21%). This compares favorably with the reported early mortality for balloon atrial septostomy. Most striking have been the length of palliation, freedom from complications, and low incidence of late death among these patients. In contrast, reported series of balloon septostomies have shown a high incidence of strokes, repeat hospitalization, inadequate palliation, and late deaths. Since palliation is reliable following a Blalock-Hanlon procedure, we do not favor early correction with hypothermic arrest but recommend it at 12 to 18 months of age, when conventional perfusion can be easily utilized.

Based upon experience with cervicothoracic esophageal carcinomas in which resection of the manubrium, adjacent clavicles, and ribs has facilitated exposure of the tumor, it has been found that a partial upper sternal split (without resection) provides access to the upper thoracic esophagus to the level of the carina. With a knowledge of the anatomic relationships of the esophagus in this area, this direct anterior approach has been used for both benign and selected malignant diseases involving the upper thoracic esophagus. A partial median sternotomy has been used in 11 patients with the following esophageal pathology: upper- and/or middle-third malignancy (six), benign upper-third stricture (three), perforation of upper-third esophagogastric anastomotic stricture (one), and cricopharyngeal achalasia in association with a chronic cervical compression fracture that prevented extension of the neck (one). The following operations were performed: blunt esophagectomy with cervical esophagogastric anastomosis (six), segmental esophageal resection with primary anastomosis (three), drainage of perforation (one), and extended cervical esophagomyotomy (one). A chylothorax developed in one patient with carcinoma, the only major postoperative complication in this group. Transient hoarseness occurred in two patients. Careful evaluation of the patient with upper thoracic esophageal pathology, focusing on the type, extent, and location of the abnormality relative to the level of the carina, as well as the habitus of the patient, often indicates that a partial sternotomy can be utilized to facilitate the operation.

Ninety-one adult patients (average age 49 years) with various benign esophageal disorders treated by total thoracic esophagectomy and a cervical esophagogastric anastomosis have been followed up with personal interviews and examinations from 6 to 104 months (average 34 months). Outpatient esophageal dilation has been used liberally for any degree of postoperative cervical dysphagia. At their latest follow-up, 39 patients (43%) eat without dysphagia; four patients (4%) have mild dysphagia necessitating no treatment; 34 patients (37%) have undergone one to three dilations during the first 6 to 12 postoperative months for intermittent dysphagia; and 14 patients (16%) have more severe dysphagia necessitating regular anastomotic dilations (two thirds of these perform home self-dilations). Mild regurgitation of gastric contents has been experienced by 27 (30%), particularly when recumbent after eating, but only four patients sleep with the head of the bed elevated to prevent nocturnal regurgitation. No patient has had pulmonary complications resulting from aspiration. Twenty patients (22%) have had varying degrees of "dumping syndrome," generally transient and well controlled with medication. Two patients have required an additional gastric drainage operation 16 months and 82 months, respectively, after the esophagectomy. At their latest evaluation, 33% of the patients weigh 3 to 83 (average 19) pounds more than they weighed preoperatively, 38% weigh 5 to 40 (average 12) pounds less, and 29% have had no change in their weight. The stomach functions well as a visceral esophageal substitute and, like the esophagus, is more thick-walled and resilient than colon. Significant gastroesophageal reflux is uncommon after a properly performed cervical esophagogastric anastomosis. Postoperative dysphagia can be minimized by attention to technique in constructing the anastomosis. These data support our belief that the stomach is the preferred organ for esophageal replacement, not only for carcinoma, but also for benign diseases as well.

Transhiatal esophagectomy without thoracotomy has been performed in 65 adult patients with dysphagia from benign esophageal disease: strictures (30), neuromotor dysfunction (24), acute iatrogenic perforation (five), acute caustic injury (four), and recurrent gastroesophageal reflux (two). Nearly 70% (45) had undergone at least one prior esophageal operation, and 26% (17) had a history of between two and four esophageal operations. The esophagus was replaced with stomach in 53 patients (82%), colon being used only when there was a history of either prior gastric resection or caustic injury to the stomach (10 patients). Intraoperative blood loss averaged 1,050 ml. Intraoperative complications included pneumothorax in 38 patients (58%) and a tracheal laceration in one patient. Postoperative complications included transient recurrent laryngeal nerve paresis (11 patients, 17%), chylothorax (four patients, 6%), anastomotic leak (four patients, 6%), and small bowel obstruction (two patients). There were five hospital deaths (8% mortality), none related to the technique of esophagectomy. Follow-up ranges from 1 to 84 months (average 28 months). Of 46 patients with a cervical esophagogastric anastomosis in the original esophageal bed, 42 have had an excellent functional result although 17 have required at least one postoperative esophageal dilation. Two have developed true anastomotic strictures. Clinically significant gastroesophageal reflux has not occurred. Transhiatal esophagectomy for benign disease is feasible and safe, even after multiple previous esophageal operations. The stomach appears to be a better visceral esophageal substitute than colon, because it allows an initially easier technical operation and superior long-term functional results.