Discrepancy in the assessment of tumor response in patients with pancreatic cancer: WHO versus RECIST criteria.

PURPOSE: The Response Evaluation Criteria in Solid Tumors (RECIST) have largely replaced the World Health Organization (WHO) criteria as a preferred method for assessing tumor response in clinical trials. We hypothesized that due to frequent asymmetric growth pattern, as well as somewhat diffuse margins of pancreatic cancer, the use of WHO vs. RECIST criteria may result in significantly different tumor response assessments. The purpose of this retrospective study was to compare the WHO (bidimensional) to RECIST (unidimensional) in assessing treatment response in pancreatic cancer patients enrolled in clinical trials. MATERIALS AND METHODS: We have evaluated the contrast- enhanced computed tomography (CT) images from 12 pancreatic cancer patients with measurable disease enrolled in two phase I/II clinical trials at the Arizona Cancer Center, between July 2000 and July 2003. The tumor measurements were re-calculated by RECIST and WHO criteria and were compared. RESULTS: In 3 out of the 12 patients (25%) there was discordant response categorization when WHO criteria were used instead of RECIST. Clinical presentations in all 3 patients were more consistent with WHO categorization. CONCLUSION: Our retrospective data analysis suggests that use of different tumor response criteria (RECIST vs. WHO) may result in different assessments of treatment efficacy in patients with pancreatic cancer on clinical trials. This finding warrants further confirmation in a larger prospectively designed trial.

Correlation of gastroesophageal reflux disease symptoms characteristics with long-segment Barrett's esophagus.

Thus far, there has been a paucity of studies that have assessed the value of the different gastroesophageal reflux disease (GERD) symptom characteristics in identifying patients with long-segment Barrett's esophagus versus those with short-segment Barrett's esophagus. To determine if any of the symptom characteristics of GERD correlates with long-segment Barrett's esophagus versus short-segment Barrett's esophagus. Patients seen in our Barrett's clinic were prospectively approached and recruited into the study. All patients underwent an endoscopy, validated GERD symptoms questionnaire and a personal interview. Of the 88 Barrett's esophagus patients enrolled into the study, 47 had short-segment Barrett's esophagus and 41 long-segment Barrett's esophagus. Patients with short-segment Barrett's esophagus reported significantly more daily heartburn symptoms (84.1%) than patients with long-segment Barrett's esophagus (63.2%, P = 0.02). There was a significant difference in reports of severe to very severe dysphagia in patients with long-segment Barrett's esophagus versus those with short-segment Barrett's esophagus (76.9%vs. 38.1%, P = 0.02). Longer duration in years of chest pain was the only symptom characteristic of gastroesophageal reflux disease associated with longer lengths of Barrett's mucosa. Reports of severe or very severe dysphagia were more common in long-segment Barrett's esophagus patients. Only longer duration of chest pain was correlated with longer lengths of Barrett's esophagus.

Non-erosive reflux disease (NERD)--acid reflux and symptom patterns.

BACKGROUND: Recent reports suggest that patients with non-erosive reflux disease (NERD) treated with anti-reflux medications show lower symptom improvement rates than patients with erosive oesophagitis treated with the same medications. AIM: To determine the acid reflux and symptom patterns of patients with NERD in comparison with those with erosive oesophagitis and Barrett's oesophagus, and to identify different NERD subgroups. METHODS: One hundred and forty-nine consecutive patients seen for classic heartburn symptoms were evaluated for the study. Oesophageal mucosal injury was assessed by upper endoscopy and classified by Hetzel-Dent criteria. Patients with Hetzel-Dent grades 0-1 were considered to have NERD. The extent of oesophageal acid exposure was determined by ambulatory 24-h oesophageal pH monitoring. RESULTS: Seventy-one patients were found to have NERD, 36 erosive oesophagitis and 42 Barrett's oesophagus. Compared with patients with erosive oesophagitis (75%) and Barrett's oesophagus (93%), those with NERD (45%) were significantly less likely to have an abnormal pH test (P = 0.0001). Patients with Barrett's oesophagus had the highest mean number of acid reflux events (210 +/- 17.7), compared with those with erosive oesophagitis (139.7 +/- 15.2) and NERD (95.3 +/- 9.4) (P = 0.0001); however, the rate of perceived acid reflux events was similar and very low in all groups (NERD, 3.6%; erosive oesophagitis, 2.9%; Barrett's oesophagus, 2.17%). NERD-positive patients (abnormal pH test) had a similar extent of oesophageal acid exposure to those with erosive oesophagitis. NERD-positive patients were more likely to demonstrate a symptom index greater than 75% than NERD-negative patients (normal pH test) (61.9% vs. 10.5%; P = 0.0001). In the NERD-negative group, those with a negative symptom index reported having heartburn at pH < 4 only 12.7% of the time, compared with 70.7% of the time in those with a positive symptom index, despite a similar mean number of heartburn episodes. CONCLUSIONS: Patients with NERD commonly demonstrate a negative pH test. Acid reflux characteristics and symptom patterns suggest a heterogeneous group of patients.

Short segment Barrett's esophagus: relationship of age with extent of intestinal metaplasia.

OBJECTIVE: Short segment Barrett's esophagus (SSBE) is defined by the presence of intestinal metaplasia in biopsies obtained from mucosa with an appearance suggestive of Barrett's that extends <3 cm into the esophagus. It has been suggested that this lesion may represent a stage in an ongoing process of Barrett's esophagus progression. If so, then the prevalence of SSBE would be expected to decrease with advancing age, and patients followed over time should exhibit an increase in the extent of columnar-lined esophagus. The aim of this study was to determine whether SSBE length progresses or regresses over time by following a prospective cohort and by assessing the relationship between age and the length, as well as prevalence of SSBE. METHODS: The study included consecutive patients who were evaluated prospectively by an upper endoscopy and were found to have SSBE between October, 1983, and December, 1999, at the Southern Arizona VA Health Care System. All patients underwent a systematic biopsy protocol, and a designated pathologist who reviewed all specimens confirmed the diagnosis of Barrett's esophagus. Patients were subsequently interviewed for demographic information. In those patients who were enrolled into our surveillance program, SSBE length was remeasured and intestinal metaplasia reconfirmed on follow-up endoscopies. RESULTS: Of 343 patients with endoscopically proven Barrett's esophagus, 116 (33.8%) were found to have SSBE. Almost all were male (97.4%) and white (85.3%), with a mean age of 60.1+/-1.0 yr. The prevalence of SSBE increased with age and reached a plateau during the seventh decade of life. One-way analysis of variance showed that there was no significant difference in the mean length of SSBE among the various age groups (p = 0.84). This trend was maintained when only the white group was assessed. Follow-up endoscopies were performed in 57 patients, revealing a mean interval of 64 months to the latest endoscopy, with no significant difference in SSBE length between the first and last endoscopy (p = 0.16). CONCLUSIONS: The prevalence of SSBE increases with age until the seventh decade of life. Finding that SSBE length does not change across the various age groups and during a 64-month mean follow-up, suggests that SSBE does not progress over time.

Preferential repair by squamous epithelium of thermal induced injury to the proximal stomach in patients undergoing ablation of Barrett's esophagus.

BACKGROUND: The presence of extensions of squamous epithelium into the proximal stomach in patients undergoing routine upper endoscopy has recently been described. The factors that may favor development of squamous epithelium within the proximal stomach remain unknown. METHODS: Patients with Barrett's esophagus who agreed to undergo ablation of Barrett's epithelium by using multipolar electrocoagulation were included. Patients were treated with a high dose of a proton pump inhibitor. The columnar-appearing mucosa was systematically treated. Occasionally, thermal injury was inadvertently induced in the proximal stomach. On endoscopy performed 4 to 6 weeks after treatment, the presence of squamous epithelium extending into the proximal stomach was documented. The use of Lugol's stain assisted in confirming the squamous nature of the abnormal tissue, which was confirmed histologically by cytokeratin immunohistochemistry. RESULTS: The 12 patients included in the study had a mean length of Barrett's epithelium of 3.8 +/- 0.7 cm. Patients were treated with omeprazole, mean dose 66 +/- 6.0 mg, and had a mean percent total time that the pH was less than 4 of 1.9 +/- 0.8. The mean length and width of gastric squamous extensions were 1.7 +/- 0.2 cm and 0.8 +/- 0.1 cm, respectively. None of the squamous extensions into the stomach were documented before mucosal ablation. The extensions stained positively for cytokeratin 13 and negatively for cytokeratin 8, thereby confirming their squamous nature. CONCLUSIONS: Thermal injury to the proximal stomach in patients undergoing ablation of Barrett's epithelium and profound acid suppression results in repair by squamous epithelium. Recognition of this lesion is essential because it may lead to confusion as to the location of the esophagogastric junction in subsequent endoscopic evaluations.

Inability to noninvasively diagnose gastric intestinal metaplasia in Hispanics or reverse the lesion with Helicobacter pylori eradication.

BACKGROUND: Helicobacter pylori infection has been linked with the development of gastric adenocarcinoma and its precursor lesion, intestinal metaplasia (IM). The presence of gastric IM is not associated with symptoms, which makes identification of individuals with this lesion difficult. It is not clear whether eradication of H. pylori infection leads to reversal of gastric IM or the potential decrease in the risk of cancer in these patients. GOALS: The purpose of this pilot study was to define the prevalence of gastric IM in a population at high risk for gastric cancer (Southwestern Hispanics), examine the ability of noninvasive testing to identify individuals with the lesion, and determine whether eradication of H. pylori infection reverses gastric IM in this population. STUDY: Subjects from the Tucson metropolitan area were recruited, and baseline data, including the presence of upper gastrointestinal (UGI) symptoms, urinary sodium, and serum pepsinogen levels, were obtained. Upper endoscopy was performed and six gastric biopsies from specific anatomic sites were obtained, followed by methylene blue staining with targeted biopsies from blue-stained mucosa. Biopsies were evaluated for the presence of H. pylori infection and gastric IM. A subset of patients with gastric IM were treated to eradicate H. pylori infection. Follow-up exams with methylene blue staining, including biopsies for histology and rapid urease testing, were performed for up to 48 months. RESULTS: There were 84 subjects with a mean age of 53.0 years; 24 (29%) had gastric IM and 65 (77%) had H. pylori. There was no significant association between gastric IM and age, gender, UGI symptoms, H. pylori, or urine sodium. There was an association identified between gastric IM and a decreased pepsinogen I:II ratio (p = 0.03). Of the 11 individuals with gastric IM treated for H. pylori infection, 9 had successful therapy and underwent at least 2 follow-up examinations. The mean length of follow-up was 3.3 years. Eight of the nine (89%) had gastric IM identified histologically at the final endoscopic exam. CONCLUSIONS: H. pylori infection and gastric IM are frequent findings in Southwestern Hispanics, a high-risk population for gastric cancer. Noninvasive testing is not clinically useful in distinguishing individuals within this group who harbor gastric IM. Although eradication of H. pylori infection may lead to a decrease in the amount of gastric IM in some individuals, the lesion may be detected in the majority of individuals after more than 3 years of follow-up. These data suggest that therapy for H. pylori may not eliminate the risk of gastric cancer once IM has developed.

Correlation of oesophageal acid exposure with Barrett's oesophagus length.

BACKGROUND: Gastro-oesophageal reflux disease (GORD) plays a major role in the development of Barrett's oesophagus. However, it has yet to be elucidated what factors determine the length of Barrett's mucosa in each individual patient. AIMS: To determine if there is a correlation between oesophageal acid exposure and the length of Barrett's mucosa. We also compared the extent of oesophageal acid exposure between patients with short segment (SSBE) and long segment (LSBE) Barrett's oesophagus. METHODS: Twenty seven patients with Barrett's oesophagus were recruited prospectively into the study from the outpatient gastroenterology clinic at the Southern Arizona VA Health Care System. Diagnosis of Barrett's oesophagus and its anatomical characteristics were determined during upper endoscopy. Ambulatory 24 hour oesophageal pH monitoring assessed the extent of oesophageal acid exposure. RESULTS: There was a significant correlation between per cent total time pH less than 4 and length of Barrett's mucosa (r=0.6234, p=0.0005). In addition, there was a significant correlation between per cent upright and supine time pH less than 4 and length of Barrett's mucosa (r=0.5847, p=0.0014 and r=0.6265 p=0.0006, respectively). Patients with SSBE had significantly less oesophageal acid exposure than patients with LSBE, in terms of both per cent total time and per cent supine time pH less than 4 (p<0.05). CONCLUSIONS: The length of Barrett's mucosa correlated with the duration of oesophageal acid exposure. Patients with LSBE experienced significantly more oesophageal acid exposure than patients with SSBE. Duration of oesophageal acid exposure appears to be an important contributing factor in determining the length of Barrett's mucosa.

Recent developments in Barrett's esophagus.

Barrett's esophagus is a precancerous condition in which the squamous esophageal epithelium is replaced by a columnar epithelium. Although different types of columnar epithelium have been described, the most frequently encountered is specialized columnar epithelium or intestinal metaplasia. Most investigators believe that increased cancer risk is only associated with this type. Esophageal adenocarcinoma is increasing in frequency in the United States and in Western Europe. Recent studies highlight the importance of gastroesophageal reflux disease in esophageal adenocarcinoma. Bile-acid reflux may also play a role. Increasing interest has been expressed in short-segment (2-3 cm) Barrett's esophagus. The contribution of short-segment Barrett's esophagus to cancer at the gastroesophageal junction is currently being studied. Although regular surveillance is often recommended, the commonness of Barrett's esophagus makes such a practice impractical for every patient. Biomarker development is needed to identify patients at greatest risk, with p53 a promising candidate based on recent studies. Initial data suggest that redox mechanisms may be involved in Barrett's esophagus. Several methods have recently been described for reversing Barrett's esophagus to squamous epithelium, but the significance of this practice in terms of reducing cancer risk remains to be demonstrated.

Failure of oesophageal acid control in candidates for Barrett's oesophagus reversal on a very high dose of proton pump inhibitor.

BACKGROUND: Normalization of oesophageal acid exposure using high dose proton pump inhibitors in patients who are candidates for ablation therapy has been suggested to be essential for successful Barrett's reversal. However, the success rate for achieving pH normalization has not been determined. METHODS: Patients with Barrett's oesophagus (2-6 cm in length) who were found to be eligible for ablation therapy using multipolar electrocoagulation were included in this prospective study. Patients underwent an upper endoscopy to determine Barrett's length and other anatomic characteristics. Biopsies were obtained to rule out dysplasia. Subsequently, patients were treated with omeprazole 40 mg b.d. Twenty-four hour oesophageal pH monitoring was performed after a mean period of 8.4 +/- 0.6 days of therapy. RESULTS: Twenty-five patients were enrolled into the study. The pH test was abnormal in four (16%) of the study subjects. An additional two (8%) patients had abnormal supine percentage time with pH less than 4. There was no significant difference in oesophageal acid control between patients with long vs. short segment Barrett's oesophagus. Elderly (> 60 years) patients tended to have less acid control than younger (

Symptom severity and oesophageal chemosensitivity to acid in older and young patients with gastro-oesophageal reflux.

INTRODUCTION: elderly patients appear to have a more aggressive form of gastro-oesophageal reflux disease than younger patients. Reduced pain perception with age is a possible underlying mechanism. AIMS: to compare the extent of oesophageal mucosal injury, acid exposure, symptom severity and perception thresholds for acid infusion in older (aged 60 or older) and younger patients with gastro-oesophageal reflux. METHODS: twenty-five younger and 23 older patients completed the study. We determined acid exposure and oesophageal mucosal injury by ambulatory 24-h oesophageal pH monitoring and upper endoscopy, respectively. We determined chemosensitivity by infusing 0.1 N hydrochloric acid into the mid-oesophagus for 10 min at 10 ml/min after a 2-min infusion of normal saline at a similar rate. We quantified acid perception thresholds by the lag time to initial typical symptom perception, intensity rating at the end of acid infusion and an acid perfusion sensitivity score, calculated from the fractional duration of symptom perception and intensity rating. RESULTS: mean percentage of total time with pH <4 was higher in the older (15.8+/-2.4) than in the younger patients (11.9+/-1.8; P = 0.18). Of the older group, 74% had erosive oesophagitis versus 64% in the younger group. Frequency of symptoms (heartburn, acid regurgitation and dysphagia) was lower in the elderly group. Older patients perceived heartburn and acid regurgitation as much less severe than younger patients (P < 0.05).Younger patients had a significantly shorter lag time to initial symptom perception (P < 0.05) and a higher sensory intensity rating (P < 0.08). The acid perfusion sensitivity score was significantly lower in the older group (P < 0.05). CONCLUSIONS: older patients with gastro-oesophageal reflux disease have reduced symptom severity for heartburn despite a tendency towards increased severity of oesophageal mucosal injury and acid exposure. Age-related reduction in chemosensitivity to acid is a possible underlying mechanism.

A collaborative end-of-life care curriculum.

Death and dying in America has received limited attention in medical education. The Southern Arizona VA Health Care System and the University of Arizona have collaborated with three nonprofit community hospice programs to develop an end-of-life care curriculum. This formal and comprehensive program is offered as a one-month elective to senior medical students, residents and fellows. The goal of the program is to improve clinical skills in caring for the dying patient and foster research in palliative and supportive care.

Beta-carotene produces sustained remissions in patients with oral leukoplakia: results of a multicenter prospective trial.

BACKGROUND: Beta-Carotene has been reported to produce regressions in patients with oral leukoplakia, a premalignant lesion. However, previous studies have all been of short duration, with clinical response as the end point. OBJECTIVE: To evaluate the duration of response and the need for maintenance therapy in subjects who respond to beta-carotene. METHODS: In this multicenter, double-blind, placebo-controlled trial, subjects were given beta-carotene, 60 mg/d, for 6 months. At 6 months, responders were randomized to continue beta-carotene or placebo therapy for 12 additional months. RESULTS: Fifty-four subjects were enrolled in the trial, with 50 being evaluable. At 6 months, 26 subjects (52%) had a clinical response. Twenty-three of the 26 responders completed the second, randomized phase. Only 2 (18%) of 11 in the beta-carotene arm and 2 (17%) of 12 in the placebo arm relapsed. Baseline biopsies were performed in all patients, with dysplasia being present in 19 (38%) of the 50 evaluable patients. A second biopsy was obtained at 6 months in 23 subjects who consented to this procedure. There was improvement of at least 1 grade of dysplasia in 9 (39%), with no change in 14 (61%). Nutritional intake was assessed using food frequency questionnaires. There was no change in carotenoid intake during the trial. Responders had a lower intake of dietary fiber, fruits, folate, and vitamin E supplements than did nonresponders. Beta-carotene levels were measured in plasma and oral cavity cells. Marked increases occurred during the 6-month induction. However, baseline levels were not restored in subjects taking placebo for 6 to 9 months after discontinuation of beta-carotene therapy. CONCLUSIONS: The activity of beta-carotene in patients with oral leukoplakia was confirmed. The responses produced were durable for 1 year.

Alpha-tocopherol supplementation for men with existing coronary artery disease: a feasibility study.

BACKGROUND: Recent studies have suggested that alpha-tocopherol supplementation can help reduce the incidence of coronary disease. Our objectives were to determine the feasibility of providing alpha-tocopherol supplements to male veterans with existing coronary artery disease and determine its effects on alpha-tocopherol levels and the susceptibility of low-density lipoprotein (LDL) to oxidation. METHODS: Fifty-seven percent of 138 coronary disease patients were willing to participate in a placebo-controlled trial -25% were already taking antioxidants. Thirty-nine men were randomly assigned to either 400 mg/day of alpha-tocopherol (n = 27) or placebo (n = 12). alpha-Tocopherol levels and LDL oxidation (measured by formation of thiobarbituric acid-reactive substance) were measured at baseline and at 6 months. RESULTS: Thirty-three subjects (22 alpha-tocopherol, 11 placebo) completed the study; 3 subjects withdrew after suffering coronary disease events. Supplement compliance exceeded 90% and alpha-tocopherol was well tolerated. The alpha-tocopherol group had a significantly greater mean increase in lipid-adjusted alpha-tocopherol levels (73% vs. -4.6%, P < 0.0001), but oxidized LDL did not change significantly. CONCLUSIONS: A secondary prevention trial among veterans would be feasible because the rates of enrollment, completion, compliance, and clinical events were high. alpha-Tocopherol supplements did not decrease the susceptibility of LDL to oxidation, suggesting that higher dosages or longer duration of supplementation may be required for secondary prevention.

Durability of new squamous epithelium after endoscopic reversal of Barrett's esophagus.

BACKGROUND: Endoscopic reversal of Barrett's esophagus with multipolar electrocoagulation and high-dose omeprazole has been previously described but long-term results are not available. The aim of this study was to follow patients after endoscopic reversal and to perform a detailed analysis of the "new" squamous mucosa. METHODS: After reversal, patients with Barrett's esophagus were maintained on high-dose omeprazole and underwent interval endoscopy, and large biopsies were obtained of the former Barrett's epithelium. RESULTS: Nine of 11 patients were men; the mean age was 62 years. The mean length of Barrett's mucosa was 4.4 cm; the mean dose of omeprazole used was 49 mg/day. All patients had an initial complete response to treatment-no evidence of Barrett's endoscopically and histologically. Three patients had intestinal metaplasia underlying the new squamous mucosa in the latest follow-up biopsies. In these 3 patients, only 0.4%, 2%, and 8% of the total biopsy area had intestinal metaplasia. All but 4 patients had underlying intestinal metaplasia at variable times during the study period. Patients have been followed for a mean of 36 months (range 19 to 53 months). CONCLUSIONS: New squamous mucosa is durable and resembles normal squamous tissue. Underlying glands of intestinal metaplasia are intermittently found. Because the significance of this residual intestinal metaplasia is unclear, surveillance endoscopy with biopsies of the treated segment is recommended even after reversal therapy.

Effect of vitamin E on exhaled ethane in cigarette smokers.

STUDY OBJECTIVES: We hypothesized that micronutrient antioxidant intake may be one factor determining the development of significant COPD. Vitamin E was administered to smokers to determine if exhaled ethane was reduced and if ethane correlated with measures of lung function. STUDY DESIGN: Longitudinal placebo lead-in trial with posttreatment observation period. SETTING: Tucson Veterans Affairs Medical Center. PARTICIPANTS: Twenty-nine current stable smokers having no interest in smoking cessation. INTERVENTIONS: Spirometry, exhaled breath ethane measurements, and vitamin E and [-carotene plasma levels followed by 3 weeks of placebo with repeat plasma vitamin levels and ethane measurements; next, 3 weeks of vitamin E (dl-a-tocopherol), 400 IU po bid followed by plasma vitamin levels and breath ethane measurements; finally, 3 weeks without vitamins followed by breath ethane and plasma vitamin levels. RESULTS: Vitamin E treatment did not reduce ethane significantly. Exhaled ethane levels (mean + SD: pm/min/kg) were as follows: baseline, 7.39 + 5.39; after run-in period, 6.86 + 4.09; after vitamin E, 6.36+/-3.02; and final, 7.23+/-4.63. After vitamin E therapy, a significant negative correlation existed between exhaled ethane and FEV1/FVC. Pack-years of smoking at baseline and after vitamin E were significantly associated with ethane exhaled. Initial lung function was not significantly negatively associated with vitamin E-induced changes in exhaled ethane but a negative trend was found. CONCLUSIONS: Vitamin E alone, unlike the combination of vitamins C, E, and beta-carotene, failed to reduced exhaled ethane in cigarette smokers. Exhaled ethane was correlated with pack-years of smoking. Smokers whose ethane values were found to fall the most tended to have better preserved lung function.

Squamous islands in Barrett's esophagus: what lies underneath?

OBJECTIVE: Squamous islands are frequently visualized at the time of upper endoscopy in patients with Barrett's esophagus, especially those on proton pump inhibitor therapy (PPI). The significance of these islands is not clearly understood. The aim of this study was to systematically biopsy macroscopic squamous islands and to examine their histologic characteristics. METHODS: Patients with Barrett's esophagus undergoing surveillance had squamous islands documented and biopsied at the time of endoscopy. Barrett's esophagus was defined as the presence of a columnar lined esophagus on endoscopy with intestinal metaplasia on biopsy. All biopsies were obtained by a single senior endoscopist and were stained with alcian blue at pH 2.5. Biopsy samples with inadequate tissue quantity were not included in the study. RESULTS: A total of 39 biopsies were obtained from 22 patients. Twenty of the 22 patients were male, with a mean age of 65.4 yr (range 47-80 yr). The mean length of Barrett's mucosa was 5.6 cm (range 1-11 cm). Eleven of 22 patients were on omeprazole (mean dose 29.1 mg/day), whereas seven patients were on lansoprazole (60 mg/day). The mean duration of PPI therapy was 2.3 yr (range 9-71 months) at the time of biopsy of the squamous islands. Three patients were on H2-blocker therapy whereas the remaining patient had not been started on acid suppression therapy. On histology, 24 biopsy specimens (61.5%) revealed only squamous epithelium, whereas 15 (38.5%) showed the presence of intestinal metaplasia underlying the squamous epithelium. There was no significant difference between the patients with and without underlying intestinal metaplasia in regard to age, Barrett's length, dose, and duration of PPI therapy. CONCLUSION: In more than one-third of biopsies of macroscopic squamous islands within Barrett's esophagus, microscopic intestinal metaplasia is detected. The presence of squamous islands should not be equated with regression of Barrett's esophagus or with decreased cancer risk.

Dysplasia in short-segment Barrett's esophagus: a prospective 3-year follow-up.

OBJECTIVE: Short segments of intestinal metaplasia in the distal esophagus are being recognized with increasing frequency. Both long and short segments of Barrett's esophagus can progress to dysplasia and cancer. However, the risk of short-segment Barrett's esophagus (SSBE) for the development of dysplasia and adenocarcinoma of the esophagus is not yet known. Our purpose, therefore, was to determine the frequency with which dysplasia occurs in patients with SSBE. METHODS: Patients with SSBE were followed prospectively for the development of dysplasia. SSBE was defined as <3 cm of Barrett's-appearing epithelium above the gastroesophageal junction at endoscopy, with intestinal metaplasia on biopsy as documented by alcian blue stain at pH 2.5 on at least two endoscopic biopsies 6 months apart. Patients had interval upper endoscopy with systematic biopsy of the Barrett's segment. RESULTS: Fifty-nine SSBE patients were identified. The mean length of Barrett's mucosa was 1.5 +/- 0.1 cm; the mean age of the patients was 63.1 +/- 1.3 yr. Five patients had low-grade dysplasia (LGD) at initial endoscopy, for a prevalence of 8.5%; none had high grade dysplasia (HGD). Thirty-two patients had follow-up endoscopy over a mean period of 36.9 +/- 5.4 months. Five of these patients developed dysplasia on follow-up, three with LGD and two with HGD, the incidence of any dysplasia being 5.7% per year. One patient with HGD that developed during surveillance progressed to adenocarcinoma of the esophagus over a 2-yr period. The other patient with HGD had LGD on follow-up endoscopy. Six patients with initial LGD had no evidence of dysplasia on follow-up. CONCLUSIONS: The prevalence of dysplasia was 8.5% with an incidence of 5.7% per year in this group of SSBE patients, followed prospectively. Although dysplastic changes may not be identified on follow-up examination, some patients progress to adenocarcinoma. Therefore, we recommend surveillance endoscopy and biopsy in patients with SSBE just as in those with long-segment Barrett's esophagus.

Increased esophageal chemoreceptor sensitivity to acid in patients after successful reversal of Barrett's esophagus.

When compared to patients with erosive esophagitis, patients with Barrett's esophagus have demonstrated reduced chemo- and mechanoreceptor sensitivity to acid infusion and balloon distension, respectively. However, anecdotal clinical experience suggested an increase in symptom perception in patients after successful elimination of Barrett's epithelium, using multipolar electrocoagulation (MPEC) and high-dose proton pump inhibitor (PPI). To determine perception thresholds to acid infusion, we evaluated eight consecutive patients after a series of MPEC treatments resulted in complete elimination of Barrett's mucosa and compared them to 10 age-matched patients with nonreversed Barrett's esophagus and 10 patients with symptomatic, endoscopy-documented erosive esophagitis (Hetzel-Dent grade 2 or greater). Chemosensitivity was determined by a modified acid perfusion test, where acid perception thresholds were quantified by the lag time to initial typical symptom perception, sensory intensity rating, and an acid perfusion sensory score (APSS). While patients after successful elimination of Barrett's esophagus had similar sensory intensity ratings and APSS as patients with erosive esophagitis, the lag times differed significantly between the groups, and both groups had significantly higher sensory intensity ratings and APSS than patients with nonreversed Barrett's esophagus. In conclusion, patients after complete reversal of Barrett's mucosa are unexpectedly as sensitive to acid as symptomatic patients with erosive esophagitis.

Lack of spontaneous regression of tubular adenomas in two years of follow-up.

OBJECTIVE: Change in colon polyp size over time has not been well characterized. It has been inferred that some polyps will increase in size, leading to an increased risk of progressing to cancer, whereas other polyps may spontaneously regress. To develop a better understanding of the natural history of colon polyps, we prospectively investigated change in polyp size over a 2-yr period. METHODS: Patients were enrolled if they had an endoscopically detected proximal rectal or sigmoid polyp measuring 3-9 mm. The index polyp site was then permanently marked with an adjacent India ink tattoo to allow definitive future localization of the polyp. Patients underwent flexible sigmoidoscopy at 6-month intervals, and at each examination, the polyp size was carefully measured with open biopsy forceps. After a maximum of 2 yr, each polyp was removed and the histology determined. RESULTS: Thirty polyps were followed in 26 patients who completed the study. Twelve polyps were tubular adenomas (TA), one was tubulovillous, 14 were hyperplastic polyps (HP), two had no pathological diagnosis, and one was a leiomyoma. HP were more likely to decrease in size than were TA. Three polyps demonstrated fast growth rates (2-4 mm/yr), and all were TA. Two polyps were removed early because their size had reached 1 cm or more. Both of those polyps were TA. No polyps regressed completely during the 2 yr of the study; neither did we find consistent linear growth rates. CONCLUSIONS: In contrast to prior reports, in this study, after polyps had been definitively localized with India ink, we observed no complete polyp regressions.