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Background The Bravo capsule allows monitoring of esophageal acid exposure over a two-day period. Experience has shown that 24–32% of patients will have abnormal esophageal acid exposure detected on only one of the 2 days monitored. This variation has been explained by the effect of endoscopy and sedation. The aim of this study was to assess the day-to-day discrepancy following transnasal placement of the Bravo capsule without endoscopy or sedation and to determine factors related to this variability. Methods Bravo pH monitoring was performed by transnasal placement of the capsule in 310 patients. Patients were divided into groups based on the composite pH score: both days normal, both days abnormal and only one of the 2 days abnormal. Lower esophageal sphincter (LES) characteristics were compared between groups. Results Of the 310 patients evaluated, 60 (19%) showed a discrepancy between the 2 days. A total of 127 patients had a normal pH score on both days and 123 had an abnormal pH score on both days. Of the 60 patients with a discrepancy, 27 were abnormal the first day and 33 (55%) were abnormal the second day. Patients with abnormal esophageal acid exposure on both days had higher degrees of esophageal acid exposure and were more likely to have a defective LES compared to those with an abnormal score on only one day (35 vs. 83%, p = 0.027). Conclusion Patients with a discrepancy between days of Bravo pH monitoring have lower esophageal acid exposure. Variability between the 2 days represents early deterioration of the gastroesophageal barrier and indicates less advanced reflux disease.

Introduction Obesity and gastroesophageal reflux disease (GERD) are increasingly important health problems. Previous studies of the relationship between obesity and GERD focus on indirect manifestations of GERD. Little is known about the association between obesity and objectively measured esophageal acid exposure. The aim of this study is to quantify the relationship between body mass index (BMI) and 24-h esophageal pH measurements and the status of the lower esophageal sphincter (LES) in patients with reflux symptoms. Methods Data of 1,659 patients (50% male, mean age 51 ± 14) referred for assessment of GERD symptoms between 1998 and 2008 were analyzed. These subjects underwent 24-h pH monitoring off medication and esophageal manometry. The relationship of BMI to 24-h esophageal pH measurements and LES status was studied using linear regression and multiple regression analysis. The difference of each acid exposure component was also assessed among four BMI subgroups (underweight, normal weight, overweight, and obese) using analysis of variance and covariance. Results Increasing BMI was positively correlated with increasing esophageal acid exposure (adjusted R2 = 0.13 for the composite pH score). The prevalence of a defective LES was higher in patients with higher BMI (p

OBJECTIVE: Surveillance, Epidemiology and End Results (SEER) data indicate that number of lymph nodes removed impacts survival in gastric cancer. Our aim was to study this relationship in esophageal cancer. METHODS: The study population included 2303 esophageal cancer patients (1381 adenocarcinoma, 922 squamous) from 9 international centers that had R0 esophagectomy prior to 2002 and were followed at regular intervals for 5 years or until death. Patients treated with neoadjuvant or adjuvant therapy were excluded. RESULTS: Operations consisted of esophagectomy with (1700) and without (603) thoracotomy. Median number of nodes removed was 17 (IQR10-29). There were 508 patients with stage I, 853 stage II, and 942 stage III. Five-year survival was 40%. Cox regression analysis showed that the number of lymph nodes removed was an independent predictor of survival (P < 0.0001). The optimal threshold predicted by Cox regression for this survival benefit was removal of a minimum of 23 nodes. Other independent predictors of survival were the number of involved nodes, depth of invasion, presence of nodal metastasis, and cell type. CONCLUSIONS: The number of lymph nodes removed is an independent predictor of survival after esophagectomy for cancer. To maximize this survival benefit a minimum of 23 regional lymph nodes must be removed

Duodenogastric-esophageal reflux disease is directly linked to Barrett's esophagus and to the development of esophageal adenocarcinoma. Despite this link, little is known about the mutagenic potential of refluxed material on the esophageal mucosa. We hypothesize that the reflux of gastric and duodenal content causes mutations in esophageal mucosa in vivo.Seven Sprague Dawley/Big Blue F1 lacI transgenic rats underwent esophagoduodenostomy (ED) to surgically create duodeno-gastric-esophageal reflux. Fourteen nonoperated rats served as negative (n = 7) and as positive (n = 7/methyl-N-amyl-nitrosamine [MNAN] intraperitoneally) controls. The animals were killed 16 weeks after operation or injection, the entire esophageal mucosa was harvested, and mutation frequency was determined through standard Big Blue Mutagenesis Assay.Gross esophagitis was evident in all operated animals. The frequency of lacI mutations in esophageal mucosal cells of animals with ED was significantly higher, nearly 1.5-fold, than that of nonoperated animals. Nitrosamine administration resulted in a nearly 20-fold increase of lacI mutation frequency. Thirteen mutations were successfully sequenced, 46% occurred at CpG dinucleotide sites and 61% were either C to T or G to A transitions.The data provide preliminary evidence of the mutagenic potential of bile reflux on esophageal epithelium. The specific mutations are markedly higher than would be expected by chance and are similar to that found in p53 mutations of human esophageal adenocarcinoma, providing a link to human esophageal cancer.

The purpose of this study was to evaluate the interindividual and intraindividual variability of slow motorized pull-through lower esophageal sphincter (LES) manometry compared to standard station pull-through LES manometry to measure LES overall length, abdominal length, and pressure and to report normal values for the slow motorized pull-through method. The slow motorized pull-through had significantly smaller coefficient of variation, indicating closer agreement between different examiners in analyzing a given tracing. The correlation coefficients for each parameter in normal subjects and symptomatic patients was significantly higher when using slow motorized pull-through for both patients and normal subjects for all three parameters. The 5th percentile of normal values obtained from 41 volunteers for LES overall length, abdominal length, and pressure was 2.7 cm, 1.4 cm, 5.1 mm Hg, respectively. The results indicate that the slow motorized pull-through method is more reproducible than the standard station pull-through method both between different observers and when the same examiner measures the same tracing on two different occasions.

Objective To evaluate the function of the vagal nerves and the gastric reservoir after vagal-sparing esophagectomy. Summary Background Data Esophagectomy as currently performed includes division of the vagal nerves and surgical alteration of the stomach, with attendant postoperative dumping, diarrhea, reduced meal capacity, and weight loss. Vagal-sparing esophagectomy has been introduced as a technique for removal of the esophagus while preserving the vagal nerves and gastric reservoir. The procedure is touted as having a low morbidity and is applicable to patients with end-stage benign or early malignant disease. Methods A random sample of 15 patients at a median of 20 months after a vagal-sparing esophagectomy was compared to 23 asymptomatic normal subjects; 10 randomly selected patients, 29 months after esophagogastrectomy with colon interposition; and 10 randomly selected patients, 47 months after standard esophagectomy with gastric pull-up. Gastric mucosal acidification was tested with Congo red staining. Vagal secretory function was measured by gastric acid output and pancreatic polypeptide response to sham feeding. Vagal motor function was assessed by a technetium gastric emptying scan and a questionnaire to evaluate dumping and diarrhea. Gastric reservoir function was evaluated by measuring meal capacity and postoperative changes in body mass index. Results Vagal-sparing esophagectomy preserved the function of the vagi, as evident by an increase in gastric acid output, a rise in serum pancreatic polypeptide following sham feeding, and preservation of normal postoperative gastric emptying in 70% of the patients. After vagal-sparing esophagectomy, patients were free of dumping and diarrhea and were analogous to normal subjects in meal capacity but had a slight reduction in the speed of eating. Conclusions Vagal-sparing esophagectomy preserves gastric secretory, motor, and reservoir function. Postoperatively, patients have normal alimentation, bowel regulation, and no weight loss. It is an ideal procedure for patients with end-stage benign disease, Barrett's esophagus with high-grade dysplasia, or esophageal carcinoma limited to the lamina propria.

Objective The need for esophagectomy in patients with Barrett's esophagus, with no endoscopically visible lesion, and a biopsy showing high-grade dysplasia or adenocarcinoma has been questioned. Recently, endoscopic techniques to ablate the neoplastic mucosa have been encouraged. The aim of this study was to determine the extent of disease present in patients with clinically occult esophageal adenocarcinoma to define the magnitude of therapy required to achieve cure. Methods Thirty-three patients with high-grade dysplasia (23 patients) or adenocarcinoma (10 patients) and no endoscopically visible lesion underwent repeat endoscopy and systematic biopsy followed by esophagectomy. The surgical specimens were analyzed to determine the biopsy error rate in detecting occult adenocarcinoma. In those with cancer, the depth of wall penetration and the presence of lymph node metastases on conventional histology and immunohistochemistry staining was determined. The findings were compared with those in 12 patients (1 with high-grade dysplasia, 11 with adenocarcinoma) who had visible lesions on endoscopy. Results The biopsy error rate for detecting occult adenocarcinoma was 43%. Of 25 patients with cancer and no visible lesion, the cancer was limited to the mucosa in 22 (88%) and to the submucosa in 3 (12%). After en bloc esophagectomy, one patient without a visible lesion had a single node metastasis on conventional histology. No additional node metastases were identified on immunohistochemistry. The 5-year survival rate after esophagectomy was 90%. Patients with endoscopically visible lesions were significantly more likely to have invasion beyond the mucosa (9/12 vs. 3/25, p = 0.01) and involvement of lymph nodes (5/9 vs. 1/10, p = 0.057). Conclusions Endoscopy with systematic biopsy cannot reliably exclude the presence of occult adenocarcinoma in Barrett's esophagus. The lack of an endoscopically visible lesion does not preclude cancer invasion beyond the muscularis mucosae, cautioning against the use of mucosal ablative procedures. The rarity of lymph node metastases in these patients encourages a more limited resection with greater emphasis on improved alimentary function (esophageal stripping with vagal nerve preservation) to provide a quality of life compatible with the excellent 5-year survival rate of 90%.

OBJECTIVE: To develop selection criteria based on the mechanical properties of pharyngoesophageal swallowing that indicate when patients with pharyngeal dysphagia will benefit from a myotomy. SUMMARY BACKGROUND DATA: The pathophysiology of pharyngoesophageal swallowing disorders is complex. The disorder is of interest to several medical specialists (gastroenterologists, otorhinolaryngologists, general and thoracic surgeons), which contributes to confusion about the entity. The management is compounded because it is most frequently seen in the elderly, is often associated with generalized neuromuscular disease, and occurs with a high prevalence of concomitant disease. The selection of patients for myotomy is difficult and of major importance to the quality of life of the affected patients. METHOD: One hundred seven patients without a Zenker diverticulum but with pharyngeal dysphagia underwent a detailed manometric assessment of the upper esophageal sphincter (UES). Cricopharyngeal opening was identified by the presence of a subatmospheric pressure drop before bolus arrival. Impaired pharyngoesophageal segment compliance resulting in a resistance to pharyngoesophageal flow was determined by measuring the intrabolus pressure generated by a 5-ml liquid bolus. RESULTS: Thirty-one of 107 patients underwent a myotomy (29%). Both impaired sphincter opening and increased intrabolus pressure predicted a good outcome. CONCLUSION: Myotomy is beneficial in patients with pharyngeal swallowing disorders and manometric evidence of defective sphincter opening and increased intrabolus pressure.

Background Lung cancer is the number one cancer killer of both men and women in the United States. Three quarters of lung cancer patients are diagnosed with regionally or distantly disseminated disease; their 5-year survival is only 15%. DNA hypermethylation at promoter CpG islands shows great promise as a cancer-specific marker that would complement visual lung cancer screening tools such as spiral CT, improving early detection. In lung cancer patients, such hypermethylation is detectable in a variety of samples ranging from tumor material to blood and sputum. To date the penetrance of DNA methylation at any single locus has been too low to provide great clinical sensitivity. We used the real-time PCR-based method MethyLight to examine DNA methylation quantitatively at twenty-eight loci in 51 primary human lung adenocarcinomas, 38 adjacent non-tumor lung samples, and 11 lung samples from non-lung cancer patients. Results We identified thirteen loci showing significant differential DNA methylation levels between tumor and non-tumor lung; eight of these show highly significant hypermethylation in adenocarcinoma: CDH13, CDKN2A EX2, CDX2, HOXA1, OPCML, RASSF1, SFPR1, and TWIST1 (p-value << 0.0001). Using the current tissue collection and 5-fold cross validation, the four most significant loci (CDKN2A EX2, CDX2, HOXA1 and OPCML) individually distinguish lung adenocarcinoma from non-cancer lung with a sensitivity of 67–86% and specificity of 74–82%. DNA methylation of these loci did not differ significantly based on gender, race, age or tumor stage, indicating their wide applicability as potential lung adenocarcinoma markers. We applied random forests to determine a good classifier based on a subset of our loci and determined that combined use of the same four top markers allows identification of lung cancer tissue from non-lung cancer tissue with 94% sensitivity and 90% specificity. Conclusion The identification of eight CpG island loci showing highly significant hypermethylation in lung adenocarcinoma provides strong candidates for evaluation in patient remote media such as plasma and sputum. The four most highly ranked loci, CDKN2A EX2, CDX2, HOXA1 and OPCML, which show significant DNA methylation even in stage IA tumor samples, merit further investigation as some of the most promising lung adenocarcinoma markers identified to date.

Objective: Living-donor lobar lung transplantation offers an alternative for patients with a life expectancy of less than a few months. We report on our intermediate results with respect to recipient survival, complications, pulmonary function, and hemodynamic reserve. Methods: Thirty-eight living-donor lobar lung transplants were performed in 27 adult and 10 pediatric patients for cystic fibrosis (32), pulmonary hypertension (two), pulmonary fibrosis (one), viral bronchiolitis (one), bronchopulmonary dysplasia (one), and posttransplantation obliterative bronchiolitis (one). Seventy-six donors underwent donor lobectomies. Results: There were 14 deaths among the 37 patients, with an average follow-up of 14 months. Predominant cause of death was infection, consistent with the large percentage of patients with cystic fibrosis in our population. The overall incidence of rejection was 0.07 episodes/patient-month, representing 0.8 episodes/patient. Postoperative pulmonary function testing generally showed a steady improvement that plateaued by postoperative months 9 to 12. Fourteen patients who were followed up for at least 1 year underwent right heart catheterization; pressures and pulmonary vascular resistances were within normal ranges. Bronchiolitis obliterans was definitively diagnosed in three patients. Among the 76 donors, complications in the postoperative period included postpericardiotomy syndrome (three), atrial fibrillation (one), and surgical reexploration (three). Conclusions: We believe that these data support an expanded role for living-donor lobar lung transplantation. Our intermediate data are encouraging with respect to the functional outcome and survival of these critically ill patients, who would have died without this option. (J Thorac Cardiovasc Surg 1996;112:1284-91)

Objectives: The role of fundoplication in patients with pure type II paraesophageal hiatal hernia remains controversial. Conventional thinking suggests that because the lower esophageal sphincter is located within the abdomen, it is competent, and fundoplication is unnecessary. Few studies have used objective evaluation to guide the addition of an antireflux procedure. Methods: Fifteen consecutive patients with type II paraesophageal hernia were treated between May 1991 and July 1994. All had radiographic criteria of pure type II hernias. Preoperative evaluation included upper intestinal endoscopy, esophageal manometry, and 24-hour ambulatory pH monitoring. The lower esophageal sphincter was considered incompetent if any of the following criteria were present: a resting pressure less than 7 mm Hg, an overall sphincter length less than 2 cm, or an intraabdominal length less than 1 cm. Primary symptoms responsible for surgery were related to the hernia in 73% of patients: dysphagia or postprandial abdominal pain in six patients, abdominal distension or vomiting in four patients, and bleeding in one patient. Symptoms typical of gastroesophageal reflux were present in four patients: heartburn and regurgitation in two each. Results: Objective evidence of gastroesophageal reflux was present in the majority of patients. Five patients (31%) had evidence of esophageal injury: esophagitis in three patients, stricture in one, and esophageal ulcer in one. In 11 of 15 patients (69%), pathologic esophageal acid exposure was detected by 24-hour pH monitoring. Twelve patients (75%) had a defective lower esophageal sphincter, usually the result of an inadequate intraabdominal length (8/12, 66%). Hernia reduction, crural closure, and Nissen fundoplication were performed in 14 patients (one patient awaits surgery). Symptomatic relief was excellent in all cases. No patient has had hernia recurrence at an average of 14 months' follow-up (range 2 to 39 months). Conclusion: Objective evaluation reveals that gastroesophageal reflux accompanies type II paraesophageal hernia in a high proportion of patients, usually because of an incompetent lower esophageal sphincter. Appropriate treatment includes reduction of the hernia, crural closure, and fundoplication in most, if not all, patients. (J Thorac C ardiovasc S urg 1996;111:655-61)

Objective Neoadjuvant therapy is commonly used for esophageal adenocarcinoma. We have reported reduced local recurrence rates and improved survival after an en bloc esophagectomy compared with a transhiatal resection as primary therapy for adenocarcinoma of the esophagus. The aim of this study was to determine whether the benefits of an en bloc resection would extend to patients after neoadjuvant therapy. Methods The charts of all patients with esophageal adenocarcinoma that had neoadjuvant therapy and en bloc or transhiatal esophagectomy from 1992–2005 were reviewed. Patients found to have systemic metastatic disease at the time of the operation or who had an incomplete resection were excluded. Results There were 58 patients: 40 had an en bloc resection and 18 had a transhiatal esophagectomy. A complete pathologic response occurred in 17 (29.3%) of 58 patients. Median follow-up was 34.1 months after en bloc resection and 18.3 months after transhiatal resection ( P = .18). Overall survival at 5 years and survival in patients with residual disease after neoadjuvant therapy was significantly better with an en bloc resection (overall survival: 51% for en bloc resection and 22% for transhiatal resection [ P = .04]; survival with residual disease: 48% for en bloc resection and 9% for transhiatal resection [ P = .02]). Survival in patients with complete pathologic response tended to be better after an en bloc resection (en bloc, 70%; transhiatal, 43%; P = .3). Conclusion An en bloc resection provides a survival advantage to patients after neoadjuvant therapy compared with a transhiatal resection, particularly for those with residual disease. Similar to patients treated with primary resection, an en bloc esophagectomy is the procedure of choice after neoadjuvant therapy.