Response evaluation by endoscopy, rebiopsy, and endoscopic ultrasound does not accurately predict histopathologic regression after neoadjuvant chemoradiation for esophageal cancer.

OBJECTIVE: To prospectively assess the sensitivity (sens), specificity (spec), positive predictive value (ppv), negative predictive value (npv), and accuracy (acc) for clinical response evaluation by endoscopy, rebiopsy, and endoscopic ultrasound (EUS) to determine histomorphologic regression UICC T-category downstaging after neoadjuvant chemoradiation for esophageal cancer. BACKGROUND: Histomorphologic regression is meanwhile established as objective parameter for response and prognosis after neoadjuvant chemoradiation for esophageal cancer. PATIENTS AND METHODS: Within a prospective observation trial, 80 patients with localized esophageal cancers (cT2-4,Nx,M0) received standardized neoadjuvant chemoradiation (cisplatin, 5-fluorouracil, 36 Gy) and were resected by transthoracic en bloc esophagectomy and two-field lymphadenectomy. Tumor regression was based on the percentage of vital residual tumor cells and classified in 4 categories as reported previously. Evaluation by endoscopy and EUS was performed based on WHO/UICC criteria before starting chemoradiation and before resection and rebiopsies were taken at the time of re-endoscopy. RESULTS: Histomorphologic response was of significant (log rank) prognostic importance (P < 0.001), whereas clinical response evaluation by endoscopy (P = 0.1), rebiopsy (P = 0.34), and EUS (P = 0.35) was not. The results of the 3 diagnostic modalities to assess histomorphologic regression by endoscopy and rebiopsy UICC ypT-category downstaging for EUS are summarized: Endoscopy: sens 60%, spec 34%, ppv 49%, npv 44%, acc 47%. Rebiopsy: sens 36%, spec 100%, ppv 100%, npv 24%, acc 47%. EUS: sens 7%, spec 79%, ppv 18%, npv 57%, acc 50%. CONCLUSIONS: Histomorphologic regression is an objective response parameter of significant prognostic importance. The diagnostic accuracy of endoscopy, rebiopsy, and EUS is inadequate for objective response evaluation after neoadjuvant chemoradiation and can be omitted for this purpose in the clinical practice.

Duodeno-gastric-esophageal reflux--what is pathologic? Comparison of patients with Barrett's esophagus and age-matched volunteers.

INTRODUCTION: The aim of the study was to analyse pH- and bile-monitoring data in patients with Barrett's esophagus and in age- and gender-matched controls. SUBJECTS AND METHODS: Twenty-four consecutive Barrett's patients (8 females, 16 males, mean age 57 years), 21 patients with esophagitis (10 females, 11 males, mean age 58 years), and 19 healthy controls (8 females, 11 males, mean age 51 years), were included. Only patients underwent endoscopy with biopsy. All groups were investigated with manometry, gastric and esophageal 24-h pH, and simultaneous bile monitoring according to a standardized protocol. A bilirubin absorption>0.25 was determined as noxious bile reflux. The receiver operator characteristic (ROC) method was applied to determine the optimal cutoff value of pathologic bilirubin levels. RESULTS: Of Barrett's patients, 79% had pathologic acidic gastric reflux (pH<4>5% of total measuring time). However, 32% of healthy controls also had acid reflux (p<0.05) without any symptoms. The median of esophageal bile reflux was 7.8% (lower quartile (LQ)-upper quartile (UQ)=1.6-17.8%) in Barrett's patients, in patients with esophagitis, 3.5% (LQ-UQ=0.1-13.5), and in contrast to 0% (LQ-UQ=0-1.0%) in controls, p=0.001. ROC analysis showed the optimal dividing value for patients at more than 1% bile reflux over 24 h (75% sensitivity, 84% specificity). CONCLUSION: An optimal threshold to differentiate between normal and pathological bile reflux into the esophagus is 1% (24-h bile monitoring with an absorbance>0.25).

Vitamin intake and risk of subtypes of esophageal cancer in Germany.

PURPOSE: The incidence of adenocarcinoma of the esophagus is increasing in most Western industrialized nations especially in white males. The impact of vitamins on the development of squamous cell carcinoma (SCC) and adenocarcinoma (AC) of the esophagus has not been elucidated. The goal of this pilot-study was to analyze the influence of daily vitamin consumption on the frequency of esophageal carcinoma in Germany. METHODS: Ninety-nine patients (males) with esophageal carcinoma (52 with SCC and 47 with AC) were compared to a control group of 50 randomly selected males from the Cologne area. Using a computer program to record the data, patients and controls were questioned in detail about their dietary habits. The interaction between known risk factors and the influence of vitamins on esophageal tumor risk were analyzed using logistic regression analysis. RESULTS: The univariate analysis showed a significant risk reduction with increased intake of beta-carotene, vitamin C, vitamin E, and folic acid for both AC and for SCC. The results of logistic regression analysis were compatible with the known risk factors for SCC (alcohol and tobacco) and for AC (obesity, tobacco, and alcohol) and showed a significant risk reduction with an intake of vitamin E greater than 13 mg/day (RR=0.13, 95% CI=0.1-0.5, P=0.0004) and vitamin C greater than 100 mg/day (RR=0.33, 95% CI=0.11-0.92, P=0.034) for patients with SCC and similar results for patients with AC. CONCLUSION: Our data showed that low intake of vitamin C and E correlates significantly with the development of squamous cell carcinoma as well as adenocarcinoma of the esophagus in males. The relevance of interaction of vitamins with other dietary factors, alcohol, and tobacco are topics of current research.

Prevalence of dysphagia in patients with gastroesophageal reflux in Germany.

Dysphagia is an alarming symptom that raises the possibility of stricture or malignancy. This study compares the prevalence and severity of dysphagia symptoms in subjects with or without gastroesophageal reflux (GERD). In a population-based study, 500 residents of Cologne between the ages of 20 and 90 years [232 (46%) males and 268 (54%) females] were randomly selected from the city register and sent questionnaires with reflux-related questions. Two hundred sixty-eight replies (54%) were accepted into the study. Of these, 45% were men with a median age of 58 years. The median female age was 54 years. Thirty-four percent of the respondents (n=92) admitted having heartburn symptoms. There was no significant gender-based difference. There was little variation in reflux frequency between individual age groups. Twenty-three (25%) of the 92 respondents with reflux reported symptoms more than twice per week. Forty-five percent of this "reflux" group took medications for their heartburn. Swallowing difficulties, predominantly mild, were reported in 11.3% of the respondents. Dysphagia was significantly increased in the reflux group (28%) versus the normal group (3%) (p<0.001). Sixteen percent of respondents with mild and 65% of those with moderate to severe reflux symptoms reported additional dysphagia symptoms (p<0.001). Swallowing problems are common in patients with GERD. Approximately two thirds of patients with long-term and severe reflux symptoms also have dysphagia symptoms. Dysphagia should always be investigated by a physician.

Bile reflux into the stomach and the esophagus for volunteers older than 40 years.

BACKGROUND: An increased incidence of Barrett's esophagus in cases with combined acidic and bile reflux is reported. The volunteers serving as controls in those studies were significantly younger than the patients. The aim of this study was to analyze bile reflux patterns of healthy volunteers aged comparably to patients with Barrett's esophagus. SUBJECTS AND METHODS: 19 older (8 f, 11 m; median age 51 years) (OV) and 20 younger (10 f, 10 m; median age 25 years) (YV) healthy volunteers without history of gastrointestinal disease or medication underwent simultaneous 24-hour pH and bile monitoring (Bilitec). All subjects consumed a special diet that did not interfere with bile measurements. Indicators for bile reflux in the stomach and esophagus: bilirubin probe absorption >0.25 in total measuring period (TM), upright position (excluding postprandial periods) (UP) and supine period (SP). RESULTS: There were no differences between older and younger volunteers in pH monitoring. Comparing the periods of bilirubin exposure of the stomach, the median (lower and upper quartile) percentage of time was OV = 5.7% (1.0-15.0%) and YV = 3.5% (0.1-7.8%) respectively for TM (n.s.), OV = 3.1% (0.7-9.4%) and YV = 0.4% (0.0-7.1%) for UP (n.s.), and OV = 2.1% (0.2-16.7%) and YV = 5.9% (0.0-12.2%) respectively for SP (n.s.). In 10/19 older volunteers and in 18/20 younger volunteers, no reflux of bile into the esophagus was measured. However, 4 older volunteers presented bile reflux from 4.6 to 51% of the total measuring period in contrast to the younger group with a maximum of 1.3% of TM. CONCLUSION: No significant differences in bile reflux into the stomach were distinguishable between younger and older healthy volunteers, but older volunteers more frequently exhibited bile reflux into the esophagus.