Jeffrey A. Hagen

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.

BACKGROUND: Recent studies based on symptomatic outcomes analyses have shown that laparoscopic repair of large type III hiatal hernias is safe, successful, and equivalent to open repair. These outcomes analyses were based on a relatively short followup period and lack objective confirmation that the hernia has not recurred. The aim of this study was to compare the outcomes of laparoscopic and open repair of large type III hiatal hernia using both symptomatic evaluation and barium study to assess the integrity of the repair. STUDY DESIGN: Fifty-four patients underwent repair of a large type III hiatal hernia between 1985 and 1998. The surgical approach was laparotomy in 13, thoracotomy in 14, and laparoscopy in 27. An antireflux procedure was included in all patients. Symptomatic outcomes were assessed using a structured questionnaire at a median of 24 months and was complete in 51 of 54 patients (94%). A single radiologist, without knowledge of the operative procedure, assessed the integrity of the repair using video esophagram. Videos were performed at a median of 27 months (35 months open and 17 laparoscopic) and were completed in 41 of 54 patients (75%). RESULTS: Symptomatic outcomes were similar in both groups with excellent or good outcomes in 76% of the patients after laparoscopic repair and 88% after an open repair. Reherniation was present in 12 patients and was asymptomatic in 7. A recurrent hernia was present in 12 of the 41 patients (29%) who returned for a followup video esophagram. Forty-two percent (9 of 21) of the laparoscopic group had a recurrent hernia compared with 15% (3 of 20) of the open group (p < 0.001 log-rank value on recurrence-free followup). CONCLUSIONS: Laparoscopic repair of type III hiatal hernias is associated with a disturbingly high (42%) prevalence of recurrent hernia. More than half such recurrences have few, if any, symptoms.

Lung cancer is the leading cause of cancer death worldwide, and adenocarcinoma is its most common histological subtype. Clinical and molecular evidence indicates that lung adenocarcinoma is a heterogeneous disease, which has important implications for treatment. Here we performed genome-scale DNA methylation profiling using the Illumina Infinium HumanMethylation27 platform on 59 matched lung adenocarcinoma/non-tumor lung pairs, with genome-scale verification on an independent set of tissues. We identified 766 genes showing altered DNA methylation between tumors and non-tumor lung. By integrating DNA methylation and mRNA expression data, we identified 164 hypermethylated genes showing concurrent down-regulation, and 57 hypomethylated genes showing increased expression. Integrated pathways analysis indicates that these genes are involved in cell differentiation, epithelial to mesenchymal transition, RAS and WNT signaling pathways, and cell cycle regulation, among others. Comparison of DNA methylation profiles between lung adenocarcinomas of current and never-smokers showed modest differences, identifying only LGALS4 as significantly hypermethylated and down-regulated in smokers. LGALS4, encoding a galactoside-binding protein involved in cell-cell and cell-matrix interactions, was recently shown to be a tumor suppressor in colorectal cancer. Unsupervised analysis of the DNA methylation data identified two tumor subgroups, one of which showed increased DNA methylation and was significantly associated with KRAS mutation and to a lesser extent, with smoking. Our analysis lays the groundwork for further molecular studies of lung adenocarcinoma by identifying novel epigenetically deregulated genes potentially involved in lung adenocarcinoma development/progression, and by describing an epigenetic subgroup of lung adenocarcinoma associated with characteristic molecular alterations.

BACKGROUND: Reports of esophageal anastomotic complications often involve more gastric than colonic reconstructions and are incomplete because of fragmented followup by physicians unfamiliar with the surgical procedure. STUDY DESIGN: Three hundred ninety-three consecutive esophagectomy patients had prevalence and risk factors determined for graft ischemia and anastomotic leak; 363 of these patients followed for more than 1 month (median 15 months) had prevalence and risk factors determined for anastomotic stricture. RESULTS: Conduit ischemia occurred in 36 (9.2%) and anastomotic leak in 43 patients (10.9%). Risk factor for ischemia was comorbid conditions requiring therapy (Odds ratio [OR]: 2.2 [95% CI 1.1-4.3]), and for leak were ischemia (OR: 5.5 [95% CI 2.5-12.1]), neoadjuvant therapy (OR: 2.2 [95% CI 1.1-4.5]), and comorbid conditions (OR: 2.1 [95% CI 1.1-3.9]). A stricture developed in 80 patients (22.0%). Risk factors were ischemia (OR: 4.4 [95% CI 2.0-9.6]), anastomotic leak (OR: 3.8 [95% CI 1.9-7.6]), and increasing preoperative weight (p = 0.022). The prevalence of ischemia was similar after gastric (10.4%) versus colonic (7.4%) reconstruction; leak and stricture were more common (14.3% versus 6.1%, p = 0.013, 31.3% versus 8.7%, p < 0.0001, respectively) and strictures were more severe (11.2% versus 2%, p = 0.001) after gastric pull-up. Patients free of ischemia and leak who developed stricture were more likely to have had a gastric pull-up (25% versus 7%, p < 0.0001). Dilatation was effective treatment in 93% of patients. CONCLUSIONS: After esophagectomy 10% of patients will develop conduit ischemia or an anastomotic leak and 22% will develop anastomotic stricture. Anastomotic leak and strictures are more common and the strictures are more severe after gastric pull-up compared with colon interposition. Dilatation is a safe and effective treatment.

OBJECTIVE: The author's goal was to determine the role of duodenal components in the development of complications of gastroesophageal reflux disease. SUMMARY AND BACKGROUND DATA: There is a disturbing increase in the prevalence of complications, specifically the development of Barrett's esophagus among patients with gastroesophageal reflux disease. Earlier studies using pH monitoring and aspiration techniques have shown that increased esophageal exposure to fluid with a pH above 7, that is, of potential duodenal origin, may be an important factor in this phenomenon. METHODS: The presence of duodenal content in the esophagus was studied in 53 patients with gastroesophageal reflux disease confirmed by 24-hour pH monitoring. A portable spectrophotometer (Bilitec 2000, Synectics, Inc.) with a fiberoptic probe was used to measure intraluminal bilirubin as a marker for duodenal juice in the esophagus. Normal values for bilirubin monitoring were established for 25 healthy subjects. In a subgroup of 22 patients, a custom-made program was used to correlate simultaneous pH and bilirubin absorbance readings. RESULTS: Fifty-eight percent of patients were found to have increased esophageal exposure to gastric and duodenal juices. The degree of mucosal damage increased when duodenal juice was refluxed into the esophagus, in that patients with Barrett's metaplasia (n = 27) had a significantly higher prevalence of abnormal esophageal bilirubin exposure than did those with erosive esophagitis (n = 10) or with no injury (n = 16). They also had a greater esophageal bilirubin exposure compared with patients without Barrett's changes, with or without esophagitis. The correlation of pH and bilirubin monitoring showed that the majority (87%) of esophageal bilirubin exposure occurred when the pH of the esophagus was between 4 and 7. CONCLUSIONS: Reflux of duodenal juice in gastroesophageal reflux disease is more common than pH studies alone would suggest. The combined reflux of gastric and duodenal juices causes severe esophageal mucosal damage. The vast majority of duodenal reflux occurs at a pH range of 4 to 7, at which bile acids, the major component of duodenal juice, are capable of damaging the esophageal mucosa.