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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.

Villin is an actin-binding cytoskeletal protein required for brush-border formation in the normal small intestinal and renal proximal tubule epithelium. Villin is a marker of cell differentiation in small intestinal and renal cell lineages, and recent studies have shown villin to be highly expressed in 100% of intestinal-type Barrett's metaplasias. This epithelium is the single greatest risk factor for developing esophageal adenocarcinoma and arises when the normal esophageal squamous epithelium is replaced by a small intestine-like columnar epithelium after damage by chronic gastroesophageal reflux. In intestinal-type Barrett's metaplasia, the villin protein exhibits a highly characteristic staining pattern in which strong apical, brush-border staining of columnar epithelial cells is observed. In this study, the ability to identify intestinal metaplastic cells by using this distinct villin staining pattern was examined in endoscopic esophageal brushings from patients with confirmed Barrett's metaplasia. Esophageal brushings from 81% (17 of 21) of patients with Barrett's metaplasia demonstrated individual columnar cells with the characteristic villin staining pattern, whereas all normal esophageal squamous cells, blood cells, and gastric columnar cells were negative for villin expression. Northern blot analysis demonstrated villin mRNA expression in Barrett's metaplasia but not in the normal squamous esophagus or gastric mucosa from the same patients. The combined use of villin immunohistochemical analysis and esophageal brush cytology may provide a simple and effective method of detecting intestinal-type Barrett's metaplasia in patients at higher risk for developing this epithelium, such as those experiencing chronic gastroesophageal reflux symptoms.

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.

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.

Achalasia is characterized by failure of relaxation of the lower esophageal sphincter and absence of progressive peristalsis in the esophageal body. Few data are available regarding the morphologic features of achalasia, in particular its histologic progression. The esophagi of 42 patients with achalasia treated with total thoracic esophagectomy were examined histologically in order to systematically identify morphologic features of clinically unresponsive achalasia and to determine what could be learned about the disease's evolution. In all cases, myenteric ganglion cells within the esophageal body were markedly diminished, with 20 specimens having none. Twenty specimens had residual ganglion cells in the proximal esophagus, and 15 specimens had a few randomly distributed ganglion cells in the mid- and distal portions of the esophagus. Inflammation within myenteric nerves, present in all cases, generally consisted of a mixture of lymphocytes and eosinophils, occasionally with plasma and mast cells. Focal replacement of myenteric nerves by collagen occurred in all cases, and there was almost complete replacement in several cases. Actual destruction of the residual ganglion cells was not seen. The resected esophagi also shared extramyenteric morphologic features. Some features probably stemmed from physiologic obstruction, such as muscular hypertrophy, mainly of the muscularis propria (all cases), with secondary degeneration and fibrosis (29 cases), and eosinophilia of the muscularis propria (22 cases). Other changes, probably resulting from chronic stasis of ingested materials in the lumen, included diffuse squamous hyperplasia (all cases), lymphocytic mucosal esophagitis (28 cases), lymphocytic inflammation of the lamina propria and submucosa with prominent germinal centers (all cases), and submucosal periductal or glandular inflammation with complete loss of submucosal glands in half of the cases. One patient had high-grade squamous dysplasia, and another had superficially invasive squamous cell carcinoma. A third group of changes was probably due to previous esophagomyotomy, including abnormal gastroesophageal reflux, as shown by pH reflux testing (13 cases) and Barrett's mucosa (four cases). In one case of Barrett's there was low-grade dysplasia. Clinically unresponsive, surgically resected achalasia has almost total loss of ganglion cells, and widespread destruction of myenteric nerves has already occurred. The only active component is myenteric inflammation. However, it cannot be determined whether this inflammation is a manifestation of ongoing nerve destruction or whether it is a secondary phenomenon.

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 most popular and widely used operations to control gastroesophageal reflux and its complications, the Nissen fundoplication, the Belsey Mark IV transthoracic hiatal hernia repair, and the Hill median arcuate ligament posterior gastropexy, share a number of common features. In each, the crura are approximated behind the esophagus, sutures are placed into either distal esophageal or periesophageal tissues, and when the repair is completed there is a 3- to 5-cm segment of distal esophagus within the abdominal cavity, where the influence of positive intraabdominal pressure contributes to the newly constructed distal esophageal high-pressure zone. Since each of these repairs requires esophageal or periesophageal sutures as well as reduction of the esophagogastric junction several centimeters below the diaphragm, any factors which jeopardize the reliability of the esophageal sutures or which produce tension on the repair can be regarded as “risk factors” which predispose the patient to disruption of the repair and recurrent gastroesophageal reflux. It has been amply documented, for example, that poor long-term reflux control is achieved when the Belsey Mark IV repair is performed in patients with esophagitis and stricture (Donnelly et al. 1973; Orringer et al. 1972).

Chylothorax is an unusual complication after transhiatal esophagectomy (THE) and in the past 10 years has occurred in 11 of 320 patients (3%) undergoing this operation for diseases of the intrathoracic esophagus. Four patients had benign esophageal disease: scleroderma reflux esophagitis (1), caustic stricture (1), and achalasia (2), and each had undergone at least one previous esophageal operation. Seven patients had intrathoracic esophageal carcinoma--two upper-third, two middle-third, and three distal-third lesions. Excessive chest tube drainage more than 72 hours after THE was the standard presentation, and the diagnosis of chylothorax was confirmed by the administration of cream through the jejunostomy feeding tube placed routinely at operation. The character of the chest tube drainage changed from serous to opalescent. Aggressive treatment of this complication was the rule, and every patient underwent a thoracotomy between 2 to 14 days (average, 6 days) after the diagnosis was established. Cream was administered through the jejunostomy tube before operation, and in each case the thoracic duct injury was readily identified and controlled with suture ligatures. There were no deaths in this group, and there was one recurrence of the fistula that required reoperation; all patients were discharged from the hospital within 3 to 29 days (average, 10 days) after thoracic duct ligation. It is concluded that early recognition of a chylothorax after transhiatal esophagectomy with prompt transthoracic ligation of the injured duct results in a shorter overall hospitalization and lower morbidity and mortality from this complication. The traditional conservative management of chylothorax with intravenous hyperalimentation and no or low-residue enteral feedings has little place in this nutritionally depleted patient population.

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.

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.

A comparison was made of the gross and microscopic wound healing and tissue reactivity between stainless steel wire, polypropylene and silk in anastomoses in the u-prepared colon of the dog. While all anastomoses healed irrespective of the suture material used, wire was associated with the least inflammatory response, silk the most and polypropylene intermediate, its low reactivity approaching that of wire. A clinical trial of Prolene for 71 varied anastomoses between pharynx, esophagus, stomach and colon in 47 patients undergoing esophageal resection and reconstruction or bypass was done. In four of the seven anastomotic disruptions which occurred, causative factors unrelated to the suture material could factorily in the remainder of these patients. Monotive suture which works well in esophageal and gastrointestinal anastomoses.

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.

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.

Substernal gastric bypass of the excluded thoracic esophagus for palliation of esophageal carcinoma was proposed as a method of providing maximum patient comfort with minimum morbidity. Our results with this operation in 37 patients are reviewed and indicate that the procedure carries unacceptable complication and mortality rates. Among our patients, there have been nine (24%) hospital deaths, seven (19%) anastomotic leaks, and six (17%) disruptions of the divided distal thoracic esophagus. Major postoperative complications have occurred in 59% of these patients. Only 15 (54%) of the 28 survivors were discharged swallowing within 3 weeks of operation, and 10 (36%) required hospitalization for 1 month or longer after operation. The average survival time in those leaving the hospital alive has been only 5.9 months. Only seven patients (25% of the survivors) have achieved good palliation with the bypass procedure. It is concluded that substernal gastric bypass of the excluded thoracic esophagus is too much of an operation for patients with unresectable tumors who have a life expectancy of only several months.

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.