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Jeffrey A Hagen

Publications and source records attributed to Jeffrey A Hagen.

At least 19 recordsLinked to original sources
PubMed2006

Clinical biology and surgical therapy of intramucosal adenocarcinoma of the esophagus.

BACKGROUND: Mucosal ablation and endoscopic mucosal resection have been proposed as alternatives to surgical resection as therapy for intramucosal adenocarcinoma (IMC) of the esophagus. Acceptance of these alternative therapies requires an understanding of the clinical biology of IMC and the results of surgical resection modified for treatment of early disease. STUDY DESIGN: Retrospective review of 78 patients (65 men, 13 women; median age 66 years) with IMC who were treated with progressively less-extensive surgical resections (ie, en bloc, transhiatal, and vagal-sparing esophagectomy) from 1987 to 2005. RESULTS: The tumor was located in a visible segment of Barrett's esophagus in 65 (83%) and in cardia intestinal metaplasia in 13 (17%). A visible lesion was present in 53 (68%) and in all but 4 the lesion was cancer. In those patients with visible Barrett's, the tumor was within 3 cm of the gastroesophageal junction in 66% and within 1 cm in 37%. Esophagectomy was en bloc in 23, transhiatal in 31, vagal-sparing in 20, and transthoracic in 4. Operative mortality was 2.6%. Vagal-sparing esophagectomy had less morbidity, a shorter hospital stay, and no mortality. Of the patients who had en bloc resection, a median of 41 nodes were removed. One patient had one lymph node metastasis on hematoxylin and eosin staining and two others, normal on hematoxylin and eosin staining, had micrometastases on immunohistochemistry. Actuarial survival at 5 years was 88% and was similar for all types of resections. Two patients died from systemic metastases and seven from noncancer causes. CONCLUSIONS: IMC occurred in cardia intestinal metaplasia and in Barrett's esophagus. Two-thirds of patients with IMC had a visible lesion. Most tumors occurred near the gastroesophageal junction. Node metastases were uncommon, questioning the need for lymphadenectomy. A vagal-sparing technique had less morbidity than other forms of resection and no mortality. Survival after all types of resection was similar. Outcomes of endoscopic techniques should be compared with this benchmark.

Adenocarcinoma↗
PubMed2006

Molecular determinants in targeted therapy for esophageal adenocarcinoma.

HYPOTHESIS: Cyclooxygenase 2 (COX-2), vascular endothelial growth factor (VEGF), and epidermal growth factor receptor (EGFR) are useful biological determinants in targeted therapy for esophageal adenocarcinoma. DESIGN: Prospective analysis. SETTING: University tertiary referral center. PATIENTS: Sixteen patients with squamous mucosa and normal results of a pH study without mucosal injury (control group), 15 with Barrett esophagus (metaplasia group), and 44 with adenocarcinoma (carcinoma group). INTERVENTIONS: Biopsy specimens were obtained 3 cm above the gastroesophageal junction. Dysplastic tissue was additionally isolated from 9 of the patients in the carcinoma group. After laser-capture microdissection, quantitative real-time polymerase chain reaction was used to measure gene expression across the spectrum of the metaplasia-dysplasia-carcinoma sequence. MAIN OUTCOME MEASURES: Expression of COX-2, VEGF, and EGFR in each patient group. RESULTS: Expression of both COX-2 and VEGF was significantly up-regulated in patients with metaplasia, dysplasia, and cancer compared with controls (P<.01). Expression levels of both were significantly higher in cancer than in the metaplasia group (P<.05) and increased sequentially from metaplasia to dysplasia to cancer. Expression of VEGF was significantly higher in the dysplastic tissue than in nondysplastic Barrett epithelium (P<.05). No change in expression levels of EGFR was seen in the histologic progression to esophageal adenocarcinoma. CONCLUSION: Gene expression data suggest that pharmacologic inhibition of COX-2 and VEGF may be useful adjuncts in targeted therapy for esophageal adenocarcinoma.

Adenocarcinoma↗
PubMed2006

Response of the lower esophageal sphincter to gastric distention by carbonated beverages.

Gastroesophageal reflux disease often occurs in patients with normal resting pressure and length of the lower esophageal sphincter. Such patients often have postprandial reflux. The mechanism of postprandial reflux remains controversial. To further clarify this, we studied the effect of carbonated beverages on the resting parameters of the lower esophageal sphincter. Nine asymptomatic healthy volunteers underwent lower esophageal sphincter manometry using a slow motorized pull through technique after ingestion of tap water and carbonated beverages. Resting pressure, overall length, and abdominal length of the lower esophageal sphincter were measured. All carbonated beverages produced sustained (20 minutes) reduction of 30-50% in all three parameters of the lower esophageal sphincter. In 62%, the reduction was of sufficient magnitude to cause the lower esophageal sphincter to reach a level normally diagnostic of incompetence. Tap water caused no reduction in sphincter parameters. Carbonated beverages, but not tap water, reduce the strength of the lower esophageal sphincter. This may be relevant to the pathogenesis of gastroesophageal reflux disease, especially in Western society.

Adult↗
PubMed2006

The impact of reflux composition on mucosal injury and esophageal function.

The components of refluxed gastric juice are known to cause mucosal injury, but their effect on esophageal function is less appreciated. Our aim was to determine the effect of acid and/or bile on mucosal injury and esophageal function. From 1993-2004, 402 patients with reflux symptoms had 24-hour pH and Bilitec monitoring, manometry, and endoscopy with biopsies. Mucosal injury (esophagitis or Barrett's esophagus) and esophageal function (lower esophageal sphincter [LES] characteristics and body contractility) in patients with acid reflux, bile reflux, or both were compared with patients without reflux. Reflux was present in 273/402 patients; of these, 37 (13.5%) had increased exposure to bile, 82 (30.0%) had increased exposure to acid, and 154 (56.4%) had increased exposure to both. Mucosal injury was most common with increased mixed acid and bile exposure, followed by acid alone, and was uncommon with bile alone (P < 0.0001). Functional deterioration paralleled mucosal injury (P < 0.0001). Mixed acid and bile exposure was present in more than half of patients with reflux and was associated with the most severe mucosal injury and the greatest deterioration of esophageal function. This suggests that composition of gastric juice is the primary determinant of inflammatory mucosal injury and subsequent loss of esophageal function.

Adult↗
PubMed2006

Modern 5-year survival of resectable esophageal adenocarcinoma: single institution experience with 263 patients.

BACKGROUND: Surgery, as the mainstay of treatment for localized esophageal cancer, is currently being challenged by the assumed high risk of esophagectomy and the poor longterm survival after resection. Epidemiologic and clinical changes over the past decade indicate that these assumptions should be reevaluated. The aim of this study was to assess the modern outcomes of esophagectomy for adenocarcinoma. STUDY DESIGN: We studied 263 consecutive patients (215 men, 48 women), who had esophagectomy for adenocarcinoma from 1992 to 2002. Ninety-seven (37%) were stage I, 63 (24%) were stage II, 93 (35%) were stage III, and 10 (4%) were stage IV. Forty-five percent (119 of 263) had curative en bloc resection, 52% (138 of 263) had node involvement, and 18% (48) received neoadjuvant therapy. RESULTS: Seventeen percent (44 of 263) of the patients were identified in a Barrett's surveillance program. The frequency of T1N0 adenocarcinoma increased over the study period (p=0.024). The overall 5-year survival was 46.5%, and for the last 5 years of the study was 50.4%. The overall 5-year survival for stage I was 81%; for stage II, 51%; for stage III, 14%; and for stage IV, 0%. Complications occurred in 61% and there were 12 perioperative deaths (4.5%). Cox proportional hazard analysis identified tumor stage and type of resection as independent predictors of survival. CONCLUSIONS: Nearly half of patients undergoing esophagectomy for adenocarcinoma survive >or=5 years. Improvements in survival are associated with increased detection of early stage disease, and a liberal use of en bloc resection. Nonsurgical treatments should be compared with these contemporary outcomes measures.

Adenocarcinoma↗
PubMed2006

Antireflux surgery normalizes cyclooxygenase-2 expression in squamous epithelium of the distal esophagus.

BACKGROUND: In some patients GERD presents with heartburn and regurgitation symptoms but a relative paucity of endoscopic and clinical findings, while in others symptoms may be minor or absent yet there is significant mucosal damage on endoscopy including the presence of Barrett's esophagus. The initial injury of gastroesophageal reflux is to the squamous esophageal mucosa, but while substantial research has been devoted to determining which genes are involved in the progression of Barrett's to dysplasia and cancer, little is known about the gene expression alterations in the squamous mucosa of patients with reflux. We hypothesized that the expression of cyclooxygenase-2 (Cox-2) might be increased in the squamous esophageal mucosal of patients with reflux, and might be a molecular indicator of reflux injury. Further, we hypothesized that Cox-2 expression in the squamous mucosa would be reduced following the elimination of reflux with an antireflux operation. METHODS: Biopsies of the distal esophageal squamous mucosa were taken 3 cm above the squamocolumnar junction (SCJ) in 28 GERD patients before and after Nissen fundoplication. Following microdissection and RNA isolation, quantitative real-time PCR was used to measure Cox-2 gene expression in paraffin-embedded (N = 16) and fresh frozen (N = 12) tissue. Biopsies from patients (paraffin N = 15, frozen N = 14) with normal acid exposure and no evidence of mucosal injury were analyzed as controls. RESULTS: Median Cox-2 expression in the squamous epithelium from paraffin embedded biopsies in patients with reflux disease was significantly increased compared to controls (p = 0.04). The presence of esophagitis or Barrett's esophagus did not significantly alter the expression of Cox-2 compared to patients with nonerosive reflux disease (NERD). After antireflux surgery median Cox-2 expression values were significantly reduced (p = 0.0003) and were normalized to levels similar to controls without reflux (p = 0.74). Similar results were observed in the prospectively obtained fresh frozen tissue. CONCLUSIONS: Cox-2 gene expression is increased in the distal esophageal squamous mucosa of most patients with GERD, and the elevation was similar whether there was mucosal injury in the form of esophagitis or Barrett's or no visible mucosal injury. This suggests that increased Cox-2 expression may serve as a molecular marker of reflux disease. The increased Cox-2 expression in patients with reflux was usually normalized following antireflux surgery. These findings demonstrate for the first time that gene expression can be altered by surgical correction of reflux. Thus, in addition to symptom control and improvement in the quality of life, perhaps future studies assessing the efficacy of antireflux therapy should also focus on the impact of the therapy on gene expression in the esophageal squamous mucosa.

Adult↗
PubMed2005

Comparison of the clinical and histological characteristics and survival of distal esophageal-gastroesophageal junction adenocarcinoma in patients with and without barrett mucosa.

BACKGROUND: The incidence of adenocarcinoma in the distal esophagus and at the gastroesophageal junction (GEJ) has been increasing in the last decades. It has been suggested that patients in whom Barrett mucosa can be identified in the surgical specimen have a better prognosis compared with those without. This has led to the belief that patients with and without Barrett mucosa may represent 2 distinct cancer types. HYPOTHESIS: Distal esophageal-GEJ adenocarcinoma with and without Barrett mucosa share the same origin, but differ only in clinical presentation and outcome. DESIGN AND SETTING: Retrospective cohort study in a university tertiary referral center. PATIENTS AND METHODS: Between 1992 and 2002, 215 patients (173 men and 42 women; median age, 66 years; age range, 26-91 years) had esophagogastrectomy for adenocarcinoma of the distal esophagus-GEJ. Patients receiving neoadjuvant chemotherapy or radiation therapy were excluded. MAIN OUTCOME MEASURES: Clinical presentation, tumor characteristics, and survival were compared in patients with Barrett mucosa (n = 140) and those without (n = 75). RESULTS: Patients with Barrett mucosa in the specimen had tumors that were diagnosed earlier; were smaller in size; earlier in stage, with fewer node metastases; and had a better 5-year survival. CONCLUSIONS: Observed differences in survival between patients with distal esophageal-GEJ adenocarcinoma with and without Barrett mucosa can be explained by earlier diagnosis. Patients without Barrett mucosa have their tumors detected later, when the disease is more advanced. This suggests the possibility that tumors without Barrett mucosa are not of a different origin, but rather are larger tumors that may have overgrown areas of Barrett mucosa.

Adenocarcinoma↗
PubMed2005

Distinct DNA methylation profiles in malignant mesothelioma, lung adenocarcinoma, and non-tumor lung.

DNA methylation markers provide a powerful tool to make diagnoses based on genetic material obtained directly from tumors or from "remote" locations such as sputum, pleural fluid, or serum. In particular when limited cell numbers are available, amplifyable DNA markers can provide a very sensitive tool for cancer detection and classification. Malignant mesothelioma (MM), an aggressive cancer strongly associated with asbestos exposure, can be difficult to distinguish from adenocarcinoma of the lung when limited material is available. In an attempt to identify molecular markers for MM and adenocarcinoma, we examined the DNA methylation status of 14 loci. Analysis of methylation levels in 10 MM and 8 adenocarcinoma cell lines showed that methylation of APC was significantly elevated in adenocarcinoma compared to MM cell lines (P=0.0003), while methylation of CDH1 was higher in MM (P<0.02). Subsequent examination of the methylation status of the 14 loci in 6 MM and 7 adenocarcinoma primary tumors, which yielded similar methylation profiles, supported these observations. Comparison of methylation in MM cell lines and tumors versus non-tumor lung tissue indicated that APC exhibits less methylation in MM (P=0.003) while RASSF1, PGR1, ESR1, and CDH1 show more methylation in MM, the latter two showing the most significant difference between the two tissue types (P< or = 0.0001). Comparison of methylation in adenocarcinoma cell lines and tumors versus non-tumor lung tissue showed methylation of ESR1, PGR1 and RASSF1 to be significantly elevated in adenocarcinoma, with RASSF1 being most significant (P=0.0002). Thus, with the examination of 14 loci, we have identified 5 candidates that show potential for distinguishing between MM, adenocarcinoma and/or non-cancer lung. Our observations support the strong potential of methylation markers as tools for accurate diagnosis of neoplasms in and around the lung.

Adenocarcinoma↗
PubMed2005

Survivin, a potential biomarker in the development of Barrett's adenocarcinoma.

BACKGROUND: Survivin, a member of the inhibitor-of-apoptosis family, is reported to be overexpressed in esophageal cancer but no data are available about its status in the metaplastic/dysplastic sequence. The aim of this study was to measure survivin gene expression in normal squamous/columnar epithelium and in the various stages of development of Barrett's adenocarcinoma. METHODS: Endoscopic biopsy or operative specimen samples from 5 tissue types were analyzed: (1) squamous epithelium from 3 cm above the gastroesophageal junction in patients with a negative pH study and no histologic injury (n = 17, pH- control); (2) antral tissue from patients with no evidence of Barrett's, dysplasia, or cancer (n = 29, antral control); (3) specialized intestinal metaplasia from patients with Barrett's esophagus (n = 16; Barrett's group); (4) low- or high-grade dysplasia (n = 12, dysplasia group), and (5) adenocarcinoma (n = 45 cancer group). After laser-capture microdissection cellular RNA was extracted from each tissue and reverse transcribed to complementary DNA. Expression levels of survivin were measured by reverse-transcription polymerase chain reaction. RESULTS: Survivin gene expression was greater in columnar (antral) compared with squamous (pH-) control tissues (P = .03). Expression in quiescent Barrett's epithelium was similar to both control tissues. Expression levels in dysplastic epithelium were greater than in squamous control (P = .01) and Barrett's tissues (P = .04), but not higher than columnar control tissues, whereas expression in adenocarcinoma was greater than all tissues except dysplasia (P < .001). CONCLUSIONS: Survivin expression may be a biomarker in the development of Barrett's adenocarcinoma that is able to distinguish between quiescent Barrett's, dysplastic Barrett's, and Barrett's adenocarcinoma.

Adenocarcinoma↗
PubMed2005

The mutagenic potential of duodenoesophageal reflux.

SUMMARY BACKGROUND DATA: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Adenocarcinoma↗
PubMed2005

Barrett's esophagus in females: a comparative analysis of risk factors in females and males.

OBJECTIVES: Gastroesophageal reflux symptoms occur with similar frequency in males and females, yet Barrett's esophagus is less common in females. The reason for this disparity is unknown. The aim of this study was to determine the factors related to Barrett's in females. METHODS: The records of 796 patients (462 male, 334 female) evaluated from 1990 to 2000 for symptoms of reflux were retrospectively reviewed. Physiologic abnormalities based on results of endoscopic, motility, pH, and Bilitec testing were identified, and factors related to the presence of Barrett's were determined using univariate and multivariate analysis. RESULTS: Females with reflux symptoms were significantly less likely to have a positive 24-h pH test, a defective lower esophageal sphincter, or a hiatal hernia than males with reflux symptoms. Further, females with reflux on the basis of an abnormal 24-h pH test had significantly less esophageal acid exposure than males with reflux. In contrast, esophageal exposure to refluxed acid and bilirubin was similar in females (n = 50) and males (n = 136) with Barrett's. On multivariable analysis increased esophageal bilirubin exposure was the only significant factor associated with the presence of Barrett's in male and female patients with reflux disease. CONCLUSIONS: Females with reflux symptoms have less esophageal acid exposure on average than males. However, females and males with Barrett's have a similar severity of reflux, and the female gender does not protect against the development of Barrett's in the setting of advanced reflux disease. Esophageal bilirubin exposure is the major risk factor for the presence of Barrett's in patients with reflux disease.

Adult↗
PubMed2004

En bloc vs transhiatal esophagectomy for stage T3 N1 adenocarcinoma of the distal esophagus.

HYPOTHESIS: En bloc esophagectomy (EBE) provides improved survival over transhiatal esophagectomy (THE) in patients with similarly sized transmural tumors (T3) and lymph node metastases (N1). DESIGN: A retrospective case-control study of 2 methods of esophageal resection for cancer. SETTING: University hospital (tertiary referral center for esophageal disease). PATIENTS: There were 49 patients (27 who underwent EBE and 22 who underwent THE) with similar T3 N1 disease and the following matched criteria: tumors of similar size and location, more than 20 lymph nodes in the surgical specimen, R0 resection, no previous chemotherapy or radiation therapy, and follow-up until death or for a minimum of 5 years. Main Outcome Measure Survival adjusted for differences in demographic and patient characteristics. RESULTS: The number of nodes harvested was greatest after EBE vs THE (median, 52 vs 29 [range, 21-85 vs 20-60]; P<.001). The median number of involved nodes was similar after EBE vs THE (median, 5 vs 7 [range, 1-19 vs 1-16]). The only 2 independent factors that affected survival in a Cox analysis were the number of involved lymph nodes (P =.01) and the type of resection (P =.03). Patients who underwent EBE had a survival benefit over those who underwent THE (P =.01). The survival benefit of EBE was seen only in patients with fewer than 9 involved lymph nodes (P<.001). CONCLUSION: En bloc esophagectomy confers a better survival than THE in patients with T3 N1 disease and fewer than 9 lymph node metastases.

Adenocarcinoma↗
PubMed2004

Increased acid exposure in patients with gastroesophageal reflux disease influences cyclooxygenase-2 gene expression in the squamous epithelium of the lower esophagus.

HYPOTHESIS: Although genetic changes associated with the progression to Barrett esophagus and adenocarcinoma have been identified, changes in gene expression associated with gastroesophageal reflux disease have not been reported. We examined expression levels of several genes important in carcinogenesis and compared expression levels with alterations in esophageal acid exposure. PATIENTS, DESIGN, AND SETTING: Prospective analysis of 61 patients initially seen with reflux symptoms at a private academic hospital. INTERVENTIONS: Paired esophageal biopsy specimens of squamous epithelium 3 cm above the squamocolumnar junction. All patients had 24-hour pH monitoring performed. MAIN OUTCOME MEASURES: Cyclooxygenase (COX) 1, COX-2, thymidylate synthase, human telomerase reverse transcriptase (hTERT), Bcl-2 protein, survivin protein, secreted protein acidic and rich in cysteine (SPARC), tetraspan (TSPAN), and caudal-type homeobox transcription factor 2 (CDX2) messenger RNA expression analysis was performed on snap-frozen, microdissected tissue using a quantitative reverse transcriptase-polymerase chain reaction method. Linear regression and the Pearson product moment correlation were used to relate gene expression to parameters of the 24-hour pH record. RESULTS: Expression levels of COX-2 correlated positively with the 24-hour pH score (r = 0.25, P =.05). There was no correlation between the expression of other tested genes and esophageal acid exposure. There was also no significant increase in COX-2 expression in patients with esophagitis or in those who used nonsteroidal anti-inflammatory drugs. CONCLUSIONS: To our knowledge, these data provide among the first reported correlation of genetic changes and increased esophageal acid exposure in patients with gastroesophageal reflux symptoms. The changes in gene expression occur before any metaplastic changes in the tissue are apparent, and may in the future be useful in predicting which patients will progress through a metaplasia-dysplasia carcinoma sequence.

Adult↗
PubMed2004

The prognostic importance of immunohistochemically detected node metastases in resected esophageal adenocarcinoma.

BACKGROUND: The number or ratio of lymph node metastases detected by hematoxylin & eosin (H&E) staining is the most important predictor of survival in esophageal cancer. The survival effect of lymph node metastases detected on immunohistochemistry (IHC) is controversial. My colleagues and I hypothesized that the extent of nodal disease determined by both H&E and IHC examination would more accurately predict survival than either technique alone. METHODS: The study population consisted of 37 patients who underwent en bloc esophagectomy as primary therapy for esophageal adenocarcinoma 5 or more years ago. All had mediastinal and upper abdominal lymphadenectomy. No patient received neoadjuvant or adjuvant therapy. Tissue blocks were sectioned for H&E staining to confirm the initial histology, and a second slide was stained with monoclonal antibodies AE1 and CAM 5.2, which are directed at a number of cytokeratin antigens. The slides were reviewed by an investigator blinded to clinical outcome. The effect of IHC staining on prognosis was assessed by comparing 5-year survival based on H&E and IHC findings. RESULTS: A total of 1,970 nodes were examined in the 37 patients. Routine H&E staining detected metastases in 29 patients (78%); the remaining 8 with N0 disease all survived at least 5 years after operation (median not reached). In the 29 patients with N1 disease, survival was 41% at 5 years. In 20 of the 29 N1 patients, metastases were detected by H&E in less than 10% of the nodes removed; 55% of the patients survived 5 years, and 39% survived 8 years. Nine of the 29 patients had metastases detected in more than 10% of the nodes removed, and all died at a median of 17 months. IHC staining was performed on the nodes from the 8 N0 patients and the 20 patients with less than 10% nodal involvement (a total of 28 patients). Additional nodal metastases, not identified on H&E examination, were found in 51 nodes from 17 patients (60.7%). Of the 8 patients who were node negative on H&E examination, 3 had metastases detected by IHC, and all survived 5 years or more free of disease. Of the 20 patients with less than 10% nodal metastases on H&E, 14 (70%) had additional metastases detected by IHC (median, 2 nodes per patient). When combined with the results of H&E staining, the node ratio remained less than 10% in 13 patients and exceeded 10% in 7. Survival in patients whose ratio remained less than 10% was significantly better than in those whose ratio exceeded 10% (actual 5-year survival, 77% vs 14%; chi2 = 4.662; p = 0.03). CONCLUSIONS: IHC staining techniques can identify nodal metastases missed by routine H&E examination in a large number of patients. The combination of H&E and IHC examination is useful in patients with less than 10% nodal involvement by H&E examination in that IHC detection of micrometastases allows classification into low-risk (> 75% survival) and high-risk (< 15% survival) groups. IHC-detected micrometastases are not of prognostic importance in N0 patients or those with greater than 10% nodal metastases on H&E.

Adenocarcinoma↗
PubMed2004

Omeprazole does not reduce gastroesophageal reflux: new insights using multichannel intraluminal impedance technology.

Proton pump inhibitors are the mainstay of medical management in gastroesophageal reflux disease. Although they provide relief from most symptoms, reflux may persist. We hypothesize that omeprazole does not reduce the total amount of gastroesophageal reflux but simply alters its pH characteristics. Six asymptomatic volunteers had combined 24-hour impedance pH monitoring before and after 7 days of omeprazole (20 mg BID). Multichannel intraluminal impedance was used to identify reflux episodes, which were classified as acid (pH < 4), weak acid (pH > 4 but decrease > 1 pH unit) and nonacid (pH > 4 and decrease < 1 pH unit) by pH measurements 5 cm above the lower esophageal sphincter (LES). A gastric pH sensor located 10 cm below the LES was used to verify the action of omeprazole. Impedance detected a total of 116 reflux episodes before and 96 episodes after omeprazole treatment. The median number of reflux episodes (18 versus 16, P = 0.4), median duration of reflux episodes (4.7 versus 3.6 minutes, P = 0.5), and total duration of reflux episodes (27.2 versus 42.4 minutes, P = 0.5) per subject were similar before and after omeprazole. Acid reflux episodes were reduced from 63% before to 2.1% after omeprazole (P < 0.0001), whereas nonacid reflux episodes increased (15% to 76%, P < 0.0001). Weak acid reflux episodes did not change (22.4% to 21.8%, P = 1.0). The proportion of reflux episodes greater than pH 4 increased from 37% to 98% (P < 0.0001). In normal subjects, omeprazole treatment does not affect the number of reflux episodes or their duration; rather it converts acid reflux to less acid reflux, thus exposing esophagus to altered gastric juice. These observations may explain the persistence of symptoms and emergence of mucosal injury white on proton pump inhibitor therapy.

Adult↗
PubMed2004

Prevalence and risk factors for ischemia, leak, and stricture of esophageal anastomosis: gastric pull-up versus colon interposition.

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.

Anastomosis, Surgical↗