Strategies to reduce pulmonary complications after transhiatal esophagectomy.

BACKGROUND: By eliminating a thoracotomy, transhiatal esophagectomy (THE) is purported to reduce postoperative pulmonary complications. However, data from many early series do not support this contention, documenting pulmonary complications in up to 50% of patients and pneumonia in 5%-20%. Since 1990, we have implemented a management strategy designed to maximize airway protection in the postoperative period. The purpose of this study was to determine the current incidence of pulmonary complications after transhiatal esophagectomy without thoracotomy. PATIENTS AND METHODS: From 1990 to 1995, 101 consecutive patients underwent THE. Surgical indications were esophageal carcinoma (90 patients) and Barrett mucosa with high-grade epithelial dysplasia (11 patients). Mean age was 60.2 ± 1.2 years; 89 patients were male. Eighty-two patients were smokers and 26 had chronic obstructive pulmonary disease (COPD). Sixty-five patients were American Society of Anesthesiologists risk score 3 or 4. Postoperatively, all patients were managed according to a standardized clinical pathway that included overnight mechanical ventilation, chest physiotherapy, video pharyngo-esophagram postoperative day 6 or 7, and graduated post-esophagectomy therapeutic diet after acceptable esophagram. RESULTS: Pulmonary complications were classified as major or minor depending upon whether or not a change in therapy was required. Ten patients (10%) had 11 major pulmonary complications. These included pneumonia (3), pleural effusion requiring drainage (4), exacerbation of COPD (2), and mucus plug requiring bronchoscopy or intubation (2). Minor pulmonary complications identified by chest film were atelectasis (97), pleural effusion (85), and pneumothorax (3). Patients with major pulmonary complications were older (69.3 ± 9.8 vs. 59.2 ± 12.1 years, p < .02) and more likely to have COPD (70% vs. 21%, p < .005) than those with only minor complications. There were 3 operative deaths; 2 caused by pneumonia and 1 by fungal sepsis in a patient who had exacerbation of COPD. Mean hospital length of stay was 13.1 ± 1.4 days. CONCLUSIONS: Minor pulmonary complications identified by chest film occur in nearly all patients undergoing THE. Strict adherence to a management protocol designed to maximize airway protection in the postoperative period results in a 10% incidence of major pulmonary complications. Older patient age and COPD are risk factors for major pulmonary complications after THE. Although pneumonia is uncommon, it remains the most frequent cause of death after THE.

Surgical repair of redundant intra-thoracic stomach after Ivor Lewis esophagectomy.

We present two patients with low esophagogastric anastomosis, redundant intrathoracic stomach, and markedly symptomatic reflux and regurgitation after Ivor Lewis esophagectomy. The diagnosis, technique of surgical revision, and outcome is discussed.

Transient esophageal obstruction in a young man: an intramural esophageal hematoma?

SUMMARY. We present a case of a 20-year-old, previously healthy, male student who presented with dysphagia secondary to mechanical esophageal obstruction that resolved spontaneously. Although our patient did not have 'classic' patient characteristics, we believe that the clinical evidence supports the conclusion that our patient was an atypical presentation of intramural esophageal hematoma.

Frequent hypermethylation of the 5' CpG island of E-cadherin in esophageal adenocarcinoma.

PURPOSE: E-cadherin, a M(r) 120,000 transmembrane glycoprotein, mediates calcium-dependent intercellular adhesion that is essential for normal tissue homeostasis. Loss of E-cadherin occurs in a variety of epithelial tumors and is correlated with invasion and metastasis. In esophageal adenocarcinoma, reduction of E-cadherin expression has been demonstrated previously, but mutations of the gene (CDH1) are rare. EXPERIMENTAL DESIGN: In this study, we used a nested PCR approach to examine the methylation status of the 5' CpG island of E-cadherin in esophageal specimens obtained from individuals with and without a history of esophageal cancer. RESULTS: In four individuals without esophageal cancer, E-cadherin was completely unmethylated in normal squamous cell-lined esophageal mucosa. In contrast, in patients with esophageal adenocarcinoma, E-cadherin was methylated in 26 of 31 (84%) tumor specimens. In the majority of cases, matched normal tissue (esophagus or stomach) from each patient was completely unmethylated. By immunostaining, methylated tumor samples demonstrated heterogeneously decreased membranous E-cadherin staining. CONCLUSIONS: These data suggest that epigenetic silencing via aberrant methylation of the E-cadherin promoter is a common cause of inactivation of this gene in esophageal adenocarcinoma.

Hospital volume is related to clinical and economic outcomes of esophageal resection in Maryland.

BACKGROUND: Previous studies have documented a relationship between hospital volume and perioperative and economic outcomes. Our objective was to determine the effect of hospital volume on outcomes of esophageal resection. METHODS: Statewide database was analyzed for patients who underwent esophageal resection in Maryland (n = 1,136 patients) from 1984 to 1999. Multivariate regression was used to determine the association of hospital volume with in-hospital mortality, length of stay, and charges after adjusting for case mix and time period. RESULTS: Unadjusted in-hospital mortality rates were lower in high volume hospitals (2.7%) than medium (12.7%) and low (16%) volume hospitals (p < 0.001). High hospital volume was associated with (1) fivefold reduction in the risk of death (odds ratio, 0.21; 95% confidence interval, 0.10 to 0.42; p < 0.001); (2) a 6-day (95% confidence interval, 5 to 7 days; p < 0.001) reduction in length of stay; and (3) $11,673 (95% confidence interval, $9,504 to $12,841; p < 0.001) decrease in hospital charges. Conclusions. Hospitals that perform high volumes of esophageal resection have superior clinical and economic outcomes. By referring these patients to high volume centers, we may improve quality and reduce costs.

Trial of a novel synthetic sealant in preventing air leaks after lung resection.

BACKGROUND: Postoperative air leaks are a major cause of morbidity after lung resections. This study was designed to evaluate the efficacy and safety of a new synthetic, bioresorbable surgical sealant in preventing air leaks after pulmonary resection. METHODS: In a multicenter trial, 172 patients undergoing thoracotomy were randomized intraoperatively in a 2:1 ratio to receive surgical sealant applied to sites at risk for air leak after standard methods of lung closure (treatment group) or to have standard lung closure only (control group). The primary outcome variable was the percentage of patients free of air leakage throughout hospitalization. Secondary outcome variables were the control of air leaks intraoperatively and the time to postoperative air leak cessation. Time to chest tube removal, time to hospital discharge, and safety outcomes were also evaluated. RESULTS: Air leaks were identified before randomization in 89 of 117 patients in the treatment group and in 39 of 55 patients in the control group. Application of the sealant resulted in control of air leaks in 92% of treated patients (p < or = 0.001). A significantly higher percentage of treated patients than control patients remained free of air leaks during hospitalization (39% versus 11%, p < or =0.001). The mean times to last observable air leak were 30.9 hours in the treatment group and 52.3 hours in the control group (p = 0.006). In the treatment group, trends were observed for reduced time to chest tube removal and earlier discharge. No significant difference was identified in postoperative morbidity and mortality between the two groups. CONCLUSIONS: Air leaks after lung resection occur in most patients. The application of this novel surgical sealant appears to be effective and safe in preventing postoperative air leaks.

Clinicopathologic and molecular analysis of high-grade dysplasia and early adenocarcinoma in short- versus long-segment Barrett esophagus.

Barrett esophagus, especially dysplastic Barrett mucosa, has been regarded as a preneoplastic lesion for esophageal adenocarcinoma. However, the etiology and pathogenesis of dysplasia and early adenocarcinoma in short- (SSBE) and long- (LSBE) segment Barrett esophagus have not been studied in detail. The aims of this study were to clarify clinicopathologic and genetic differences between high-grade dysplasia (HGD) and early adenocarcinoma in SSBE versus LSBE. We analyzed the clinicopathologic features from 47 patients (19 SSBE [<3 cm] and 28 LSBE [> or =3 cm]) with esophagectomy for HGD/T1 adenocarcinoma. Allelic losses on chromosomes 3p (FIHT), 5q (APC), 9p (p16), and 17p (p53) were compared in 12 HGD and 9 T1 tumors from 19 cases of SSBE and in 23 HGD and 15 T1 tumors from 28 cases of LSBE. Patients with SSBE were more likely to be smokers than were patients with LSBE (94.7% v 57.1%; P =.004). HGD or T1 tumors arising from SSBE were less likely to show adjoining nondysplastic Barrett mucosa than those from LSBE (73.6% v 100%; P =.02). LSBE more frequently showed a circumferential pattern of Barrett mucosa than did SSBE (96.4% v 47.3%; P =.0002). Chromosomal allelic losses on 3p, 5q, 9p, and 17p were detected in 19% (4 of 21), 43% (15 of 35), 40% (14 of 35), and 48% (16 of 33) of HGD, respectively, and 26% (5 of 19), 35% (8 of 23), 35% (8 of 23), and 57% (13 of 23) of T1 tumor, respectively. There were no significant differences in allelic loss of 3p, 5q, 9p, or 17p in HGD or T1 tumors from SSBE versus LSBE. These results suggest that both HGD and early adenocarcinoma in SSBE and LSBE may occur through similar genetic alterations, whereas there are some clinicopathologic differences between SSBE and LSBE. HUM PATHOL

Intensive care unit physician staffing is associated with decreased length of stay, hospital cost, and complications after esophageal resection.

OBJECTIVE: To determine whether having daily rounds by an intensive care unit (ICU) physician is associated with clinical and economic outcomes after esophageal resection. DESIGN: ICU information was obtained from a prospective survey and linked to retrospective patient data from the Maryland Health Services Cost Review Commission. The main outcome variables were in-hospital mortality rate, length of stay, hospital cost, and complications after esophageal resection. SETTING: Nonfederal acute care hospitals in Maryland that performed esophageal resection (n = 35 hospitals) during the study period, 1994-1998. PATIENTS: Adult patients who underwent esophageal resection in Maryland (n = 366 patients) from 1994 to 1998. INTERVENTIONS: Presence vs. absence of daily rounds by an ICU physician. MEASUREMENTS AND MAIN RESULTS: After adjusting for patient case-mix and other hospital characteristics, lack of daily rounds by an ICU physician was independently associated with a 73% increase in hospital length of stay (7 days; 95% confidence interval [CI], 1-15; p =.012) and a 61% increase in total hospital cost ($8,839; 95% CI, $ 1,674-$19,192; p =.013), but there was no association with in-hospital mortality rate. In addition, the following postoperative complications were independently associated with lack of daily rounds by an ICU physician: pulmonary insufficiency (odds ratio [OR], 4.0; CI, 1.4-11.0), renal failure (OR, 6.3; CI, 1.4-28.7), aspiration (OR, 1.7; CI, 1.0-2.8), and reintubation (OR, 2.8; CI, 1.5-5.2). CONCLUSIONS: Having daily rounds by an ICU physician is associated with shorter lengths of stay, lower hospital cost, and decreased frequency of postoperative complications after esophageal resection. Healthcare providers and policymakers should use this information to help improve quality of care and reduce costs for patients undergoing high-risk surgical procedures.

Solitary pulmonary lymphangioma.

Lymphangioma is an abnormal collection of lymphatics that are developmentally isolated from the normal lymphatic system. Lymphangioma rarely presents as a solitary pulmonary lesion. We present a case of solitary pulmonary lymphangioma and review the literature on its pathogenesis, clinical features, and radiographic findings.

Pulmonary artery aneurysm in a pregnant woman.

We present a patient with a pulmonary artery (PA) aneurysm who has none of the documented causes of PA aneurysm but who is pregnant. We believe that this patient represents a case of primary pregnancy-associated PA aneurysm.

Esophagectomy for adenocarcinoma in patients 45 years of age and younger.

Esophageal adenocarcinoma in patients 45 years of age or younger is uncommon. We reviewed our experience with the surgical management of these patients to determine their clinical characteristics, pathologic findings, and treatment results. Thirty-two patients were identified through our surgical pathology database, and their medical records were reviewed to determine clinical characteristics, treatment, treatment-associated mortality, tumor staging, presence of Barrett's mucosa, and survival. In our series, patients were white (100%) males (96.9%) with a history of reflux (56.3%), cigarette smoking (40.6%), and alcohol consumption (59.4%), who presented with progressive solid food dysphagia (78.1%). A prior diagnosis of Barrett's mucosa or use of antireflux medications was noted in five patients each (15.6%). There were no operative deaths. Actuarial survival was 81.1% (95% confidence interval [CI] 66.1 to 96.2) at 12 months, 68.5% (95% CI 49.5 to 87.5) at 24 months, and 56.9% (95% CI 34.6 to 79.1) at 60 months. Our findings show that patients with esophageal adenocarcinoma 45 years of age or younger have similar clinical findings to those reported in other large series where the median age is in the sixth or seventh decade of life, supporting a uniform theory of tumor pathogenesis. Esophagectomy may be performed with low mortality, and survival is reasonable for early-stage disease. Young patients with Barrett's esophagus are not immune from the development of adenocarcinoma and need to be screened accordingly.

Percutaneous replacement jejunostomy after esophagogastrectomy.

A surgically placed jejunostomy tube is a safe and effective means of delivering nutritional support for the postesophagogastrectomy patient. We have previously described a method that permits percutaneous replacement of surgically placed jejunostomy feeding tubes, and now present our results with the use of this technique in 350 consecutive esophagogastrectomy patients. Replacement jejunostomy as required in 17 patients (4.9%). All patients had successful percutaneous jejunostomy replacement. There were no procedural complications or deaths. The timing of feeding tube replacement following esophagogastrectomy was predictive of the indication. Before 16 weeks, the indication for feeding tube replacement was intubation and inability to eat (1 patient) or anorexia with weight loss and dehydration (7 patients). At or after 16 weeks, the indications for feeding tube replacement were all related to symptoms resulting from recurrent carcinoma. We conclude that the technique of percutaneous jejunostomy allows the surgeon tremendous flexibility in the management of the postesophagogastrectomy patient as it preserves the advantages of an adjuvant surgically placed feeding tube over the lifetime of the patient. The technique is safe, and the success rate is excellent.

Mutations in beta-catenin and APC genes are uncommon in esophageal and esophagogastric junction adenocarcinomas.

Beta-catenin plays important roles in both intercellular adhesion and signal transduction. Mutations in the beta-catenin or adenomatous polyposis coli (APC) gene can alter the degradation of beta-catenin and cause aberrant accumulation of beta-catenin result in increased transcription of target genes. The dysregulated APC/beta-catenin pathway has been recently discovered as an important mechanism of tumorigenesis in various cancers, but its role in esophageal adenocarcinomas is not clear. Therefore, we studied the beta-catenin gene mutation, allelic loss of chromosome 5q, and APC gene mutation in esophageal and esophagogastric junction adenocarcinomas. Two (2%) somatic mutations in exon 3 of the beta-catenin gene, encompassing the region for glycogen synthase kinase-3beta phosphorylation, were detected from 109 adenocarcinomas. Chromosomal allelic loss on 5q was frequent in 45.3% (44/97) of tumors. Only one missense mutation in the mutation cluster region of the APC gene was detected from 38 esophageal and esophagogastric junction adenocarcinomas with the 5q allelic loss. Our results based on partial screening mutational analyses indicate that mutations of APC/beta-catenin pathway, unlike in colorectal carcinoma, involve only a small subset of esophageal and esophagogastric junction adenocarcinoma.

As originally published in 1994: Simplified, standardized technique for cervical esophagogastric anastomosis. Updated in 2000.

Using transhiatal esophagectomy, the ease of performing the cervical esophagogastric anastomosis varies greatly depending on neck size, length of mobilized stomach, and adhesions from previous neck operations. We therefore have developed a technique, used in 45 consecutive patients undergoing transhiatal esophagectomy, that has simplified the technical performance of cervical esophagogastric anastomosis.

Prevalence of aspiration and laryngeal penetration in patients with unilateral vocal fold motion impairment.

The adverse consequences of aspiration in regard to patient health and quality of life are well documented. It is generally accepted that the probability of aspiration is increased in patients with unilateral vocal fold motion impairment, however, the incidence and proposed mechanism of aspiration vary depending on the reported series. We reviewed the cine or video pharyngoesophagographic findings in patients with documented unilateral vocal fold motion impairment, identified through the Johns Hopkins Hospital Swallowing Center database, to determine the prevalence and cause of aspiration and laryngeal penetration. Aspiration and laryngeal penetration were identified in 38% and 12% of patients, respectively. Aspiration resulted from impaired airway protection, not from esophageal obstruction with laryngeal "spill-over." The number and degree of impairments directly correlated with probability of aspiration. Obstruction potentiated the likelihood of aspiration. Video pharyngoesophagography accurately identifies patients at risk for aspiration.

The role of laparoscopy in preoperative staging of esophageal cancer.

BACKGROUND: Diagnostic laparoscopy has been used to determine resectability and to prevent unnecessary laparotomy in patients with advanced esophageal cancer. The objective of this prospective study was to evaluate the role of laparoscopy in conjunction with computed tomography (CT) scan in staging patients with esophageal cancer. METHODS: From March 1995 to October 1998, 59 patients with biopsy-proven esophageal cancer underwent diagnostic laparoscopy with concurrent vascular access device and feeding jejunostomy tube placement. RESULTS: Laparoscopy changed the treatment plan in 10 of 59 patients (17%). Of the patients with normal-appearing regional or celiac nodes, 78% were confirmed by biopsy to be tumor free, whereas 76% of patients with abnormal-appearing nodes were confirmed by biopsy to have node-positive disease. CONCLUSIONS: Diagnostic laparoscopy is useful for detecting and confirming nodal involvement and distant metastatic disease that potentially would alter treatment and prognosis in patients with esophageal cancer.

Neoadjuvant chemoradiation followed by surgery for resectable esophageal cancer.

Neoadjuvant chemoradiation (NAC) therapy protocols were developed to improve survival in patients with resectable esophageal cancer. Our experience with two consecutive NAC therapy trials is reviewed. Both studies included patients with localized squamous cell cancer and adenocarcinoma. Patients were treated with cisplatinum 26 mg/m2/day (days 1-5 and 26-30), 5-Fluorouracil (5-FU) 300 mg/m2/day (days 1-30), concurrent radiotherapy (4400 cGy) followed by esophagectomy. In the second trial, adjuvant taxol was added. The first protocol had 50 patients. Two patients died, both before surgery, one from sepsis. There was no residual viable tumor (CR) in 19 (40%) patients. The median survival time was 31 months. The 5-year survival rate of 36% compared favorably with concurrent 5-year survival of 18% for surgery alone. Forty-one patients were enrolled in the second trial. All underwent surgery. There were no treatment or operative deaths. Survival data for this group is maturing. Combined results from both protocols are: treatment mortality of 2.2%, complete response rate of 37%, and a median and 3-year disease-specific survival of 42 months and 54%, respectively. We conclude that NAC followed by surgery improves survival over surgery alone and that CR is predictive of improved survival.

Phase II evaluation of preoperative chemoradiation and postoperative adjuvant chemotherapy for squamous cell and adenocarcinoma of the esophagus.

PURPOSE: This phase II trial evaluated continuous-infusion cisplatin and fluorouracil (5-FU) with radiotherapy followed by esophagectomy. The objectives of this trial were to determine the complete pathologic response rate, survival rate, toxicity, pattern of failure, and feasibility of administering adjuvant chemotherapy in patients with resectable cancer of the esophagus treated with preoperative chemoradiation. PATIENTS AND METHODS: Patients were staged using computed tomography, endoscopic ultrasound, and laparoscopy. The preoperative treatment plan consisted of continuous intravenous infusion of cisplatin and 5-FU and a total dose of 44 Gy of radiation. Esophagogastrectomy was planned for approximately 4 weeks after the completion of chemoradiotherapy. Paclitaxel and cisplatin were administered as postoperative adjuvant therapy. RESULTS: Forty-two patients were enrolled onto the trial. Of the 39 patients who proceeded to surgery, 29 responded to preoperative treatment: 11 achieved pathologic complete response (CR) and 18 achieved a lower posttreatment stage. Five patients had no change in stage, whereas eight had progressive disease (four with distant metastases and four with increases in the T and N stages). At a median follow-up of 30.2 months, the median survival time has not been reached and the 2-year survival rate is 62%. The median survival of pathologic complete responders has not been reached, whereas the 2-year survival rate of this group is 91% compared with 51% in patients with complete tumor resection with residual tumor (P =.03). CONCLUSION: An excellent survival rate, comparable to that of our prior preoperative trial, was achieved with lower doses of preoperative cisplatin and 5-FU concurrent with radiotherapy.