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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.

Barrett's metaplasia consists of columnar epithelium that replaces the normal esophageal mucosa in patients with chronic gastroesophageal reflux. Because intestinal-type Barrett's metaplasia is the major risk factor for adenocarcinoma development, understanding the mechanisms that predispose the esophageal mucosa to malignant degeneration is clinically important. Glutathione s-transferase (GST)-pi belongs to a class of protective enzymes whose activity has been shown to be much lower in Barrett's metaplasia than in the normal esophagus, where this form of GST is predominant. In the studies described here, using immunocytochemical analysis, we observed higher levels of cytoplasmic GST-pi protein in normal esophageal mucosa than in Barrett's metaplasia. Using northern blot analysis, we also observed lower GST-pi mRNA levels in Barrett's metaplasia than in normal esophagus or adenocarcinomas from the same patients. Using as model systems three Barrett's adenocarcinoma cell lines and short-term organ culture of freshly resected normal esophagus and Barrett's metaplasia, dose-dependent induction of GST-pi mRNA was observed by using butylated hydroxyanisole and dexamethasone. GST-pi mRNA in Barrett's metaplasia was induced up to 2.5-fold with 60 microM butylated hydroxyanisole and nearly fivefold with 320 nM dexamethasone after 24 h. These studies demonstrate the ability to induce protective GST-pi in Barrett's metaplasia and may suggest a mechanism for future chemoprevention studies in patients with this type of epithelium, which is at high risk for malignant degeneration.

The identification of markers that distinguish primary pulmonary adenocarcinomas from pulmonary adenocarcinomas secondary to the digestive tract would be clinically important. Villin, a specific marker in digestive-tract malignancies, was evaluated in 57 pulmonary adenocarcinomas, six samples of proximal bronchial tissue, and five metastatic pulmonary adenocarcinomas (three colon and two esophageal adenocarcinomas) by using immunohistochemical and molecular analyses. Villin was expressed in 31.6% (18 of 57) of the pulmonary adenocarcinomas and showed either a diffuse cytoplasmic pattern (10.5%) or a primary cytoplasmic pattern with minor brush-border staining (21.1%). However, none of those samples demonstrated the primary brush-border staining pattern that was characteristic of all five of the metastatic digestive-tract adenocarcinomas. There was a significant difference in the positive brush-border staining pattern between the primary and metastatic pulmonary adenocarcinomas (P0.002). Villin protein was expressed in bronchial epithelial cells, and villin mRNA was detected by reverse transcription-polymerase chain reaction. Northern analysis demonstrated 3.5- and 2.7-kb villin mRNAs in villin protein-positive tumors, but villin mRNA was not detected in non-tumorous lung tissue, indicating the transcriptional upregulation of villin in lung tumors. An additional smaller-sized mRNA (1.8 kb) was observed in six of 10 pulmonary adenocarcinomas and in the bronchoalveolar carcinoma cell line A549. Two small villin mRNAs were cloned from the cell line A549 and were found to represent an alternatively spliced (exon 8-exon 14) 1.85-kb mRNA and a 1.8-kb mRNA that was missing a portion of the 5' region (exon 1-exon 9) of the native villin mRNA. These studies demonstrated that the pattern of villin expression and the presence of altered villin mRNAs may be useful markers for pulmonary adenocarcinomas as well as provide support for the potential origin of villin-expressing tumors from bronchial epithelial cells.

The molecular genetic mechanisms underlying esophageal cancer are poorly understood. However, a novel gene that may be involved in esophageal carcinogenesis was recently localized by others to distal 17q by linkage analysis of kindreds with palmoplantar keratoderma and squamous cell carcinoma of the esophagus. To help determine whether a distal 17q gene may also be involved in the pathogenesis of primary Barrett's esophageal and gastric cardia adenocarcinomas, we performed loss of heterozygosity (LOH) analysis of 21 Barrett's and 18 gastric cardia adenocarcinomas at loci spanning 17q: cen-BRCA1-SSTR2-D17S2058-D17S929-D17S722-+ ++D17S937-D17S802-tel. Over 50% of the Barrett's and cardia adenocarcinomas demonstrated loss of an allele at one or more informative distal 17q markers. One common overlapping region of loss involved loci mapped to distal 17q24-proximal 17q25, which tentatively defines a potential chromosomal region distal to BRCA1 involved in the pathogenesis or progression of both types of adenocarcinomas. LOH analysis of DNA from matched microdissected sections of Barrett's metaplasia suggested that loss of D17S2058 in this region may be an early event in the malignant transformation of Barrett's metaplasia. No statistically significant correlations between 17q LOH and tumor stage or patient survival were noted. In summary, LOH mapping of 17q in Barrett's and cardia adenocarcinomas suggests the existence of at least one putative distal 17q tumor suppressor gene involved in the pathogenesis of these tumors.

Villin is a cytoskeletal protein that is involved in the formation of brush-border microvilli in normal small intestine and colon epithelium. This protein is present in Barrett's metaplasia but is reported not to be expressed in Barrett's adenocarcinoma. In this study, we analyzed villin protein expression in Barrett's metaplasia and in both Barrett's adenocarcinomas and tumors of the gastric cardia. Immunohistochemical analysis was used to evaluate the expression and cellular localization of the villin protein in 21 cases of Barrett's metaplasia, 30 cases of Barrett's adenocarcinoma, 16 cases of gastric cardia adenocarcinoma, and eight cases of adenocarcinoma of the distal esophagus. Southern, northern, and western blot analyses were used to evaluate the potential mechanisms for regulation of villin protein expression. Villin protein expression was observed in 21 of 21 cases (100%) of intestinal-type Barrett's metaplasia and in 28 of 30 cases (93%) of Barrett's adenocarcinoma and was thus highly expressed in these tumors. Northern blot analysis demonstrated villin mRNA (3.5 and 2.7 kb) in both villin-positive Barrett's metaplasia and adenocarcinomas. Western blot analysis with the antibody used for immunohistochemical analysis confirmed the presence of a single villin protein band of 95 kDa. Abundant villin expression also was present in both adenocarcinoma of the gastric cardia (13 of 16 cases; 81%) and distal esophageal adenocarcinomas of unknown origin (six of eight cases; 75%). The intestinal brushborder enzyme sucrase isomaltase was found to be present in only 22 of 46 cases (48%) of the adenocarcinomas that expressed villin. We concluded that the protein villin is highly expressed in Barrett's adenocarcinomas and is well maintained in these and other esophageal tumors.

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.

Alterations in the tumor suppressor gene p53 may represent a useful prognostic marker of premalignant or malignant disease in Barrett's dysplasia or esophageal adenocarcinoma. Immunohistochemistry was used to establish the ability to detect nuclear accumulation of altered p53 protein in esophageal brushings as well as biopsies, and to examine for p53 alterations in a group of 18 patients with Barrett's esophagus enrolled in a surveillance and endoscopy program, p53 protein accumulation was easily detected in esophageal brushings, and the results correlated well with matched biopsies (9/11). In patients enrolled in surveillance endoscopy, 1 brushing of 22 was positive for p53 protein accumulation. In this patient, who received preoperative radiation and chemotherapy, the positive p53 result correlated with positive cytology for residual adenocarcinoma. All Barrett's esophagus brushings negative for p53 protein were benign by cytologic, morphologic criteria. The immunohistochemical detection of p53 alterations in esophageal brushing and biopsy specimens may provide useful information in patients undergoing surveillance for esophageal dysplasia and adenocarcinoma.

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

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.

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.

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.

In order to answer this question, the clinical characteristics of adenocarcinoma arising in Barrett’s esophagus must be defined (Table 1). Patients with such adenocarcinoma generally have an average age of 61 years. Barrett’s esophagus is predominantly a disease of white males, and I have been unable to find a single case report of esophageal adenocarcinoma in a black patient. This is a striking contrast to the predominance of black males among patients with squamous cell carcinoma of the esophagus. The male to female ratio in patients with adenocarcinoma in Barrett’s esophagus is about 4–5 to 1.

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.

In 84 patients with suspected intrathoracic neoplasms we compared the accuracy of conventional radiography, 55 degrees posterior oblique tomography, and contrast-enhanced dynamic incremental computed tomography (CT) in evaluation of the pulmonary hilum. We found dynamic incremental CT to be better than either conventional radiography or oblique tomography in hilar evaluation. In addition, significant information was detected in extrahilar and extramediastinal locations by CT in 21% of patients. This study, unlike earlier reports, indicates a role for CT in hilar evaluation.