Search

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.

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.

Anterior mediastinal tracheostomy is not a commonly performed operation. The procedure, however, clearly facilitates resection of cervicothoracic, tracheal, and esophageal malignancies. Of 49 cervical exenterations performed, in 35 (71%) a concomitant mediastinal tracheostomy was performed, similar to the 77% rate of mediastinal tracheostomy with cervical exenteration reported by Grillo and Mathisen. There is little question that anterior mediastinal tracheostomy combined with cervical exenteration, transhiatal esophagectomy, and a primary pharyngogastric anastomosis is a formidable technical exercise. Although this operative approach provides effective palliation and occasionally cure in patients with compromise of their airway, swallowing ability, or both, careful patient selection, meticulous attention to operative detail, and intensive postoperative care are mandatory in order to achieve a successful outcome with acceptable morbidity and mortality rates.

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.

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.

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.

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

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.

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.

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.

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.

The combined Collis gastroplasty-Nissen fundoplication consists of a combination of an esophagus-lengthening Collis gastroplasty with 360 degrees complete Nissen fundoplication operation. This report reviews the clinical and radiographic features of 60 consecutive patients who underwent this operation for the control of symptomatic gastroesophageal reflux. The surgical procedure, the technique of postoperative radiographic examination, normal radiographic anatomy, and abnormalities detectable radiographically are briefly described. All patients were examined on the seventh postoperative day initially with iodinated water-soluble contrast medium followed by barium to establish integrity of the gastroplasty tube, fundoplication wrap, and dilated esophageal stricture. Later in the postoperative period, elective barium esophagrams were prompted by complaints of dysphagia (three patients) and symptoms of gastroesophageal reflux (five patients).

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.

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.

Cardiac paragangliomas are extremely rare neoplasms. Four surgically resected tumors were examined by immunohistochemistry and electron microscopy. The patients ranged in age from 18 to 36 years. All patients had hypertension and elevated urine catecholamine levels. Three tumors were located on the posterior left atrium, and one tumor was located in the interventricular groove at the aortic root. The tumors ranged in size from 5 to 7 cm, and they displayed a prominent Zellballen pattern without significant necrosis or mitosis. The tumors were mostly unencapsulated and infiltrated adjacent cardiac tissue in two cases. Immunoperoxidase staining showed that all tumors were positive for chromogranin and neuron-specific enolase. Three tumors were positive for methionine enkephalin. Positive staining for S-100 protein was seen in the sustentacular cells of all tumors but was negative in chromaffin cells. All tumors were negative for insulin, glucagon, gastrin, vasoactive intestinal polypeptide, somatostatin, adrenocorticotropic hormone, calcitonin, serotonin, pancreatic polypeptide, and rat atrial peptide. Ultrastructural studies of all four tumors showed moderate numbers of predominantly norepinephrine-type granules and a few epinephrine-type granules. These results show that cardiac paragangliomas are commonly found in close proximity to the left atrium and have immunohistochemical and ultrastructural features similar to other paragangliomas.

Blunt injuries to the ascending aorta and branches of the aortic arch are unusual but must be considered in any victim of a high speed decelerating injury. Because there are no characteristic clinical or roentgenographic findings, aortography is the only definitive method of establishing the diagnosis. Aortography should therefore, be performed upon any patient who has had a high speed decelerating injury, regardless of the clinical or the roentgenographic findings. An early operation will prevent exsanguination.

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.

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.