Histologic Evidence Of Esophagitis Research Articles

Histologic Study of the Esophagogastric Junction of Organ Donors Reveals Novel Glandular Structures in Normal Esophageal and Gastric Mucosae.

INTRODUCTION:Whether cardiac mucosa at the esophagogastric junction is normal or metaplastic is controversial. Studies attempting to resolve this issue have been limited by the use of superficial pinch biopsies, abnormal esophagi resected typically because of cancer, or autopsy specimens in which tissue autolysis in the stomach obscures histologic findings.METHODS:We performed histologic and immunohistochemical studies of the freshly fixed esophagus and stomach resected from 7 heart-beating, deceased organ donors with no history of esophageal or gastric disease and with minimal or no histologic evidence of esophagitis and gastritis.RESULTS:All subjects had cardiac mucosa, consisting of a mixture of mucous and oxyntic glands with surface foveolar epithelium, at the esophagogastric junction. All also had unique structures we termed compact mucous glands (CMG), which were histologically and immunohistochemically identical to the mucous glands of cardiac mucosa, under esophageal squamous epithelium and, hitherto undescribed, in uninflamed oxyntic mucosa throughout the gastric fundus.DISCUSSION:These findings support cardiac mucosa as a normal anatomic structure and do not support the hypothesis that cardiac mucosa is always metaplastic. However, they do support our novel hypothesis that in the setting of reflux esophagitis, reflux-induced damage to squamous epithelium exposes underlying CMG (which are likely more resistant to acid-peptic damage than squamous epithelium), and proliferation of these CMG as part of a wound-healing process to repair the acid-peptic damage could result in their expansion to the mucosal surface to be recognized as cardiac mucosa of a columnar-lined esophagus.

1710 Symptomatic Concomitant Sarcina Associated Erosive Esophagitis and Refractory Helicobacter pylori Gastritis

INTRODUCTION: Sarcina is a gram-positive, non-motile, anaerobic cocci that was first identified in the gastric contents of humans by John Goodsir in 1842. Since then, its precise pathogenetic role in humans still remains unclear, as clinical observations have ranged from asymptomatic to life-threatening complications such as gastric perforation and emphysematous gastritis. Our review of literature yielded a total of 7 case reports which reported 8 patients with Sarcina on esophageal biopsies. Two of these had concomitant H. pylori gastritis. We report the third case of Sarcina of the esophagus associated with H. pylori gastritis. CASE DESCRIPTION/METHODS: A 70-year-old woman presented to the Gastroenterology clinic with an increase in abdominal discomfort, nausea, and vomiting over the past several months. She had previously been taking Omeprazole for reflux symptoms without relief and Naproxen for joint pain. She underwent an EGD, which showed erythematous mucosa in the distal esophagus, gastropathy, and a hiatal hernia. Targeted esophageal and gastric mucosal biopsies showed erosive esophagitis with many colonies of Sarcina species and chronic gastritis with H. pylori infection, respectively. Patient was prescribed tetracycline, metronidazole, and bismuth subsalicylate for two weeks and her omeprazole increased to twice daily for treatment of both infections. After completing the treatment regimen, the patient reported having little improvement in symptoms. Repeat EGD showed normal appearing mucosa of the esophagus, stomach, and duodenum. Esophageal biopsies showed normal squamous mucosa. Gastric biopsies showed persistent H. pylori gastritis. She was started on a salvage treatment regimen of levofloxacin, amoxicillin, and omeprazole for two weeks. Repeat testing was noted for persistent H. pylori infection. DISCUSSION: In our case, we treated our patient with antibiotics and a proton pump inhibitor, which covered for both Sarcina and H. pylori infections. However, minimal improvement in our patient's symptoms despite successful Sarcina eradication and persistent H. pylori infection suggests that although there was endoscopic and histologic evidence of esophagitis, the majority of patient symptoms were likely due to H. pylori or non-infective etiology. This finding supports those who favor Sarcina to being a benign pathogen in the GI tract. It is unclear if H. pylori gastritis in any way can be associated with Sarcina esophagitis, but this case definitely raises a question.

Tu1588 Usefulness of Japan Esophageal Society Classification of Magnified Endoscopy for the Diagnosis of Superficial Esophageal Squamous Cell Carcinoma

Grades of dysplasia can help predict risk of EA. Pathologists cannot distinguish regenerative changes from true dysplasia in up to 20% of patients (Indeterminate for dysplasia -IND). The rate of progression and clinical significance of IND are uncertain. Endoscopic surveillance and treatment patterns are also not standardized. Objectives: To understand the practice patterns and clinical outcomes for patients with BE IND. Methods: We conducted a retrospective study of patients with BE with IND from 2000-2010 at one university referral center. Statistical analysis was performed with SPSS (17.0). Results: 322 patients with BE were identified. 48 patients with IND on index EGD were identified. 24 patients were excluded since they had other degrees of dysplasia prior to or at the time of index EGD. All patients were non-Hispanic white (75% males, median age 53). 14 patients had a documented diagnosis of GERD (58%). 17 patients were on a PPI (71%). 14 patients (58%) had a recommendation for follow up after the first EGD (median 46 weeks, 6-104 weeks). The median actual follow up EGD was 40 weeks (range 12-108). Findings on repeat EGD included IND (23%), no dysplasia (46%), and low grade dysplasia (LGD) (31%). Of the patients who continued to have surveillance EGD, almost 50% had no dysplasia on subsequent biopsies. Endoscopic surveillance intervals ranged from every 2 months to every 16 months. Only 1 patient had high grade dysplasia (HGD) with an incidence of 14.3 patients per 1000 person-year. 11 patients had histologic evidence of esophagitis on the index EGD (46%). Patients without dysplasia on the 2nd EGD were more likely to have had histologic evidence of esophagitis on the 1st EGD. None of the patients with LGD on the 2nd EGD had histologic evidence of esophagitis on the 1st EGD. All patients with persistent IND or documented progression of dysplasia had a hiatal hernia. Patients who progressed to LGD or continued to have IND were more likely to be on a PPI. Immunohistochemical staining for biomarkers was performed on the initial biopsy of 12 out of 14 patients who had a second EGD. p53, -methylacylcoenzyme A racemase (AMACR), and beta-catenin were positive in 9 (75%), 7 (58%), and 6 (50%) patients. All 3 markers were positive in the patient who progressed to HGD. Re-examination of H&E slides by 2 pathologists confirmed indefinite of dysplasia in 12 out of 13 patients. Conclusions: Patients with IND may be at low risk of progression to HGD. Significant variation in endoscopic surveillance patterns for IND was found. Biomarkers may help predict progression of dysplasia. More research is needed to better understand this population and guide resource utilization in patients with BE.

Pediatric Patients With Dyspepsia Have Chronic Symptoms, Anxiety, and Lower Quality of Life as Adolescents and Adults

Little is known about long-term health outcomes of children with dyspeptic symptoms. We studied the natural history of pediatric patients with dyspeptic symptoms, with and without histologic reflux, compared with healthy controls. We performed a prospective study of consecutive new patients, ages 8-16 years, who underwent evaluation for dyspepsia, including upper endoscopy. Patients were assigned to groups with histologic evidence of reflux esophagitis (n = 50), or normal histology results (n = 53). Healthy children were followed up as controls (n = 143). Patients and controls were evaluated 5-15 years later. They provided self-reports on severity of dyspeptic symptoms, use of acid suppression, quality of life, anxiety, and depression. When the study began, the groups with histologic evidence of esophagitis and normal histologies did not differ in severity of dyspeptic symptoms, functional disability, or depression. After a mean 7.6-year follow-up period, each group had significantly lower quality-of-life scores and more severe dyspeptic symptoms and functional disability than controls, but did not differ significantly from each other; both groups were significantly more likely than controls to meet criteria for an anxiety disorder. At time of follow-up evaluation, use of acid-suppression medication was significantly greater in the group with histologic evidence for esophagitis, compared with patients who had normal histology findings when the study began. Among pediatric patients with dyspepsia evaluated by endoscopy and biopsy, those with histologic evidence for esophagitis or normal histology findings are at increased risk for chronic dyspeptic symptoms, anxiety disorder, and reduced quality of life in adolescence and young adulthood.

Use of Narrow Band Imaging (NBI) To Detect Esophagitis in Non Erosive Reflux Disease (NERD)

Purpose: Most patients with reflux symptoms do not have signs of mucosal injury on routine endoscopy. In patients with non erosive reflux disease (NERD) chromoendoscopy with Lugol's iodine and confocal laser endomicroscopy have been reported to identify lesions with histologic evidence of esophagitis. However, both procedures are time consuming and require the use of contrast agents. Narrow band imaging (NBI) is known to display macroscopic lesions such as ulcers with high contrast and clarity. We report our findings in an initial group of patients with persistent reflux symptoms and a normal esophagus on white light (WL) endoscopy to see if erosive lesions could be detected with high contrast NBI endoscopy. Methods: The Olympus GIF-H180 gastroscope was used in five patients; 3 male, 2 female, with a mean age of 49 (range 22–63) who underwent upper endoscopy for persistent reflux symptoms (heartburn at least 3 times per week for more than 3 months). On finding no evidence of esophagitis on WL endoscopy in all 5 patients, the NBI mode was switched on and the esophagus re-examined. Any discrete lesions were photographed and biopsies taken with cold forceps for histology. If no lesions were seen, biopsies were taken from the distal esophagus. Results: In asymptomatic individuals, NBI displays the normal esophagus with an even blue color. On switching to narrow band imaging (NBI) mucosal breaks or erosions were seen in 4 out of 5 patients (80%). These consisted of: 1) discrete, depressed erosions of up to 1 mm in diameter, surrounded by an even, bluish appearing normal squamous mucosa; 2) larger, flat, depressed, magenta colored patches of up to 10 mm in diameter, with visible raised margins. Targeted biopsies from these lesions showed microscopic evidence of reflux esophagitis in all 4 patients (100%). Biopsies from the distal esophagus of the patient without mucosal lesions were normal. Conclusion: These early findings suggest that high contrast imaging methods such as NBI may be useful in unmasking subtle erosive changes in the esophagus of patients with reflux symptoms that are not readily visible on routine white light endoscopy. High contrast imaging with NBI is a rapid and easy technique that does not require complex instrumentation or dyes. If these initial findings are verified by future studies, this may become a useful technique for identifying erosive lesions and targeting biopsies in patients with presumed NERD.

Pulmonary Aspiration Shown by Scintigraphy in Gastroesophageal Reflux-Related Respiratory Disease

Gastroesophageal reflux (GER) may underlie respiratory manifestations via vagally mediated airway hyperresponsiveness or microaspiration, and intraesophageal pH monitoring is generally used to identify GER in patients with such manifestations. We aimed to establish the frequency of retrograde pulmonary aspiration in patients with unexplained respiratory manifestations. Fifty-one patients with refractory respiratory symptoms (cough, n = 18; pneumonia, n = 14; apnea, n = 8; asthma, n = 7; and laryngitis, n = 4) were prospectively evaluated. They underwent 24-h intraesophageal pH monitoring and gastroesophageal 99Tc scintigraphy with lung scan 18 to 20 h after the test meal. Thirteen of 51 patients (25.5%) had abnormal intraesophageal pH study results (mean reflux index, 11.3%; range, 6.5 to 50%); and in 25 of 51 patients (49%), overnight scintigraphy showed pulmonary aspiration. Nineteen of these 25 patients had entirely normal pH study results, whereas 6 of 13 patients with abnormal pH study results had aspiration. Pulmonary aspiration was demonstrated in all patients with apnea and 61.5% of patients with recurrent pneumonia. Nine of 25 patients (36%) with aspiration had histologic evidence of esophagitis, whereas histologic esophagitis was present in 5 of 13 patients (38.4%) with pathologic GER as shown by intraesophageal pH monitoring. Pulmonary aspiration as demonstrated by overnight scintigraphy is common in children with unexplained and refractory respiratory manifestations, suggesting that GER could be the underlying cause of these manifestations. Since only a few children with chronic or recurrent respiratory symptoms have a pathologic gastroesophageal acid reflux, a normal intraesophageal pH study result does not rule out GER in these children.

Esophageal food impaction in children.

To determine the clinical presentation, radiographic, endoscopic and manometric findings, and clinical outcome of esophageal food impaction (EFI) in pediatric patients. We retrospectively reviewed the clinical course of 12 pediatric patients with EFI over a 10-year period. All 12 patients described initially presented to our emergency department for care. Four patients (25%) required previous endoscopic intervention for disimpaction of EFI. Eleven required endoscopic removal of their EFI, and 1 patient's food impaction resolved spontaneously. The mean duration of food impaction was 20 hours prior to endoscopic intervention. Endoscopy demonstrated an esophageal stricture in 1 patient with a history of trisomy 21 and tracheoesophageal fistula repair. While there was no visual evidence of esophagitis in any patient, 5 of 7 had histologic evidence of esophagitis. Upper gastrointestinal series demonstrated the esophagus to be anatomically normal in 10 of 12 patients (83%); 1 patient had an esophageal stricture and another an esophageal web. Four of 8 patients studied had nonspecific esophageal motility abnormalities. EFI in children is not generally associated with underlying esophageal anatomic abnormalities. Esophagitis and nonspecific esophageal motility disorder abnormalities may be etiologic factors. Endoscopic removal of the EFI was safe and effective and is recommended as there is little likelihood of spontaneous resolution of EFI in children.

Esophagitis impairs esophageal smooth muscle reactivity in the rat model: an in vitro study.

The present study investigated how reflux-induced esophagitis affects the smooth muscle reactivity of the esophageal body. Two different esophagitis models were used: acid gastric and mixed duodenogastric reflux. All test animals apart from the controls developed gross and histologic evidence of esophagitis. Contractile (carbachol and KCI) and relaxant (isoproterenol) esophageal smooth muscle responses were significantly decreased in the presence of acid- and mixed reflux-induced esophagitis. Similar relaxant responses to serotonin and papaverine were found in the three groups. Our study demonstrated impaired esophageal smooth muscle reactivity when esophagitis was induced by acid or mixed reflux. These changes may correspond to the functional motor abnormalities of the esophagus seen in patients with reflux esophagitis.

Abnormalities in gastrointestinal motility are associated with diseases of oxidative phosphorylation in children.

Disorders of the mitochondrial electron transport chain enzymes of oxidative phosphorylation (OXPHOS) have neurologic, musculoskeletal, ophthalmologic, cardiac, and GI manifestations. Many adult and pediatric patients with disorders of OXPHOS have abnormalities in intestinal motility. The purpose of this study was to describe pediatric patients who initially presented with signs of GI dysmotility and were later evaluated and found to have a disorder of OXPHOS. Data were collected on six patients, including initial GI and neurologic symptoms, histology of skeletal muscle biopsies, mitochondrial DNA mutational analysis, OXPHOS enzyme assay, upper GI barium imaging, technetium-99M liquid gastric emptying scan, upper GI endoscopy, esophageal manometry, and antroduodenal manometry. All six children presented with symptoms of GI dysmotility within 2 wk of life. Patients later developed symptoms of neurologic disorders. All patients had abnormalities in OXPHOS enzyme analysis. Muscle histology showed nonspecific changes with no ragged red fibers. Sequencing of the mitochondrial DNA showed no recognized mutations. No patient had any evidence of intestinal obstruction or malrotation by upper GI barium imaging. Four patients had delayed gastric emptying. Three patients had endoscopic and histologic evidence of esophagitis. All six had demonstrable neuropathic abnormalities by antroduodenal manometry, including the following: nonpropagated antral bursts, absent migrating motor complexes, postprandial antral hypomotility, retrograde migrating motor complexes, and tonic contractions with the migrating motor complex. Abnormalities in GI motility may be an early presenting sign of disorders of OXPHOS in children.

Abnormalities in gastrointestinal motility are associated with diseases of oxidative phosphorylation in children

Objective Disorders of the mitochondrial electron transport chain enzymes of oxidative phosphorylation (OXPHOS) have neurologic, musculoskeletal, ophthalmologic, cardiac, and GI manifestations. Many adult and pediatric patients with disorders of OXPHOS have abnormalities in intestinal motility. The purpose of this study was to describe pediatric patients who initially presented with signs of GI dysmotility and were later evaluated and found to have a disorder of OXPHOS. Methods Data were collected on six patients, including initial GI and neurologic symptoms, histology of skeletal muscle biopsies, mitochondrial DNA mutational analysis, OXPHOS enzyme assay, upper GI barium imaging, technetium-99M liquid gastric emptying scan, upper GI endoscopy, esophageal manometry, and antroduodenal manometry. Results All six children presented with symptoms of GI dysmotility within 2 wk of life. Patients later developed symptoms of neurologic disorders. All patients had abnormalities in OXPHOS enzyme analysis. Muscle histology showed nonspecific changes with no ragged red fibers. Sequencing of the mitochondrial DNA showed no recognized mutations. No patient had any evidence of intestinal obstruction or malrotation by upper GI barium imaging. Four patients had delayed gastric emptying. Three patients had endoscopic and histologic evidence of esophagitis. All six had demonstrable neuropathic abnormalities by antroduodenal manometry, including the following: nonpropagated antral bursts, absent migrating motor complexes, postprandial antral hypomotility, retrograde migrating motor complexes, and tonic contractions with the migrating motor complex. Conclusion Abnormalities in GI motility may be an early presenting sign of disorders of OXPHOS in children.

Role of food protein intolerance in infants with persistent distress attributed to reflux esophagitis

Distressed behavior is common in infants and is often attributed to gastroesophageal reflux (GER) or food protein intolerance. To examine the effect of a hypoallergenic amino acid-based infant formula (AAF) on distressed behavior and GER symptoms in infants who failed to respond to extensively hydrolyzed formula and antireflux medications. Nineteen distressed infants (9 boys and 10 girls; median age, 5.0 months) with presumed GER underwent gastroscopy (n = 17) and esophageal 24-hour pH monitoring (n = 14). Double-blind placebo-controlled (DBPC) formula challenges of AAF versus previously besttolerated formula were conducted. Nine infants had histologic evidence of esophagitis, and 9 had inflammatory changes in the stomach and/or duodenum. Symptoms remitted in all infants within 2 weeks of the start of feeding with AAF. On DBPC challenge after a median period of 3 months of receiving AAF, 12 infants were intolerant to active formula (distress score, 287 vs 580 min/wk,P =. 01; symptom score, 23.1 vs 36.1, P =.03). Seven infants did not relapse and were considered tolerant (distress score, 470 vs 581, P =.77; symptom score, 29.5 vs 20.2; P =.89). Treatment with AAF may reduce distressed behavior and symptoms of GER in infants with food protein intolerance.

Efficacy and safety of omeprazole for severe gastroesophageal reflux in children

Omeprazole, a potent inhibitor of acid secretion, is effective in adults with severe gastroesophageal reflux, but no such data are available on children. We studied 15 children in whom treatment with histamine (type 2) blockers and prokinetic agents had failed; 4 had also had one or more fundoplications. Their ages were 0.8 to 17 years (mean, 8.1 years) and weights were 7.5 to 30.7 kg (mean, 18.6 kg). Of the 15 children, 8 were neurologically handicapped. All patients had endoscopic and histologic evidence of esophagitis; most had esophagitis grade 3 to 4. Patients were initially given omeprazole at 10 to 20 mg; the dose was titrated upward until results of a subsequent 24-hour intraesophageal pH study was normal. Symptoms and signs abated and evidence of esophagitis diminished in all patients. Omeprazole was given for periods of 5.5 to 26 months (mean, 12.2 months). The effective total dose was 20 to 40 mg (0.7 to 3.3 mg/kg) in 11 patients, 10 mg (0.7 mg/kg) in 1 patient, and 60 mg (1.9 to 2.4 mg/kg) in 3 patients. The dosage range was 0.7 to 3.3 to mg/kg per day (mean, 1.9 mg/kg). Mildly elevated transaminase values in 7 patients and elevated fasting gastrin levels in 11 patients were present; in 6 of the 11, gastrin levels were 3 to 5.5 times the upper limit of normal. We found omeprazole to be highly effective in this group of patients with severe esophagitis refractory to other measures. We recommend a starting dose of 0.7 mg/kg as a single morning dose; the adequacy of reflux control is then determined by follow-up 24-hour intraesophageal pH studies. Omeprazole appears to be safe for short-term use, but further studies are needed to assess long-term safety because the significance of chronically elevated gastrin levels in children is unknown.

Esophagitis and esophageal motor abnormalities in patients with chronic spinal cord injuries

To investigate the frequency and severity of esophagitis and esophageal dysmotility in patients with chronic spinal cord injury (SCI), 46 males with chronic SCI completed a questionnaire regarding gastrointestinal symptomatology. Eleven of these patients subsequently underwent upper gastrointestinal (GI) endoscopy with esophageal biopsies and 10 of the 11 also had esophageal motility studies. A significantly higher percentage of SCI patients experienced heartburn (SCI 61%; controls (C) 40%), esophageal chest pain (SCI 33%; C 6.4%), and intermittent dysphagia (SCI 30%; C 8.5%). Forty-five percent of SCI patients had endoscopic evidence of mild esophagitis, and 91% of them had histologic evidence of esophagitis. SCI patients had low amplitude, slowly propagating abnormal (double-peaked) peristatic esophageal contractions. We conclude that SCI patients experience significantly more esophageal symptoms than controls. They have a higher incidence of esophagitis and esophageal motor abnormalities. The clinical relevance of these abnormalities remains to be evaluated.

Gastroesophageal physiology after stapled gastroesophagostomy in dogs

A stapled vertical gastroesophagostomy (VGE) has been proposed for benign esophageal stricture. The VGE involves performing an anastomosis using a linear cutting stapler inserted via a gastrotomy (one limb in the esophagus, the other in the proximal fundus). In phase I of the study, a 50-mm VGE was performed in 13 dogs; 7 received an additional fundoplication. Endoscopy with pinch biopsies, esophageal manometry, and 4-hour ambulatory pH recordings were performed in each dog prior to and 1 month after VGE. The only difference between groups postoperatively was a higher lower esophageal sphincter pressure in the group with the added fundoplication. The incidence of histologic esophagitis was low in both groups. In phase II of the study, a VGE was performed in six dogs using a 75-mm linear cutting stapler, accompanied by fundoplication in each dog. These dogs were then followed for 6 months to more completely assess the long-term risk of developing reflux esophagitis. At necropsy, no gross or histologic evidence of esophagitis was found. The performance of a VGE through the lower esophageal sphincter in normal dogs does not result in significant reflux esophagitis. VGE may be an alternative to resection for esophageal stricture.

Esophageal Chest Pain in Children with Asthma

Sixteen patients with asthma and chest pain of greater than 2 months duration underwent gastroenterological evaluation utilizing fiber-optic esophagogastroduodenoscopy (EGD), esophageal manometry, and Bernstein testing. Eleven of 16 patients (75%) had endoscopic and histologic evidence of esophagitis. One patient with esophagitis exhibited high-amplitude peristaltic contractions during motility testing. Four of these 11 patients (36%) had a positive Bernstein test. Extended intraesophageal pH monitoring of seven patients with esophagitis revealed significant gastroesophageal reflux (GER) in all of these patients. Chest pain was associated with an episode of GER in three patients (43%). Nine of 11 patients (82%) with esophagitis responded to medical therapy, resulting in resolution of esophageal inflammation and chest pain. One patient required Nissen fundoplication surgery after failure of medical therapy, and one patient who refused surgery progressively developed more severe esophagitis during 9 months of medical therapy. Children with asthma may have chest pain due to gastroesophageal reflux-associated esophagitis that usually responds to medical therapy.

Esophageal Chest Pain in Children with Asthma

SummarySixteen patients with asthma and chest pain of >2 months duration underwent gastroenterological evaluation utilizing fiber‐optic esophagogastroduodenoscopy (EGD), esophageal manometry, and Bernstein testing. Eleven of 16 patients (75%) had endoscopic and histologic evidence of esophagitis. One patient with esophagitis exhibited high‐amplitude peristaltic contractions during motility testing. Four of these 11 patients (36%) had a positive Bernstein test. Extended intraesophageal pH monitoring of seven patients with esophagitis revealed significant gastroesophageal reflux (GER) in all of these patients. Chest pain was associated with an episode of GER in three patients (43%). Nine of 11 patients (82%) with esophagitis responded to medical therapy, resulting in resolution of esophageal inflammation and chest pain. One patient required Nissen fundoplication surgery after failure of medical therapy, and one patient who refused surgery progressively developed more severe esophagitis during 9 months of medical therapy. Children with asthma may have chest pain due to gastroesophageal reflux‐associated esophagitis that usually responds to medical therapy.

Natural history and significance of esophageal squamous cell dysplasia

Balloon-mesh cytologic screening for esophageal cancer done in 255 asymptomatic high-risk United States veterans (age greater than 40 years, ethanol abuse for greater than 20 years, and cigarette smoking greater than 20 pack years) identified 37 patients with squamous cell dysplasia. Of the 37 patients with dysplasia, 28 were re-evaluated prospectively at 6-month intervals for up to 36 months by balloon-mesh cytology, esophagoscopy with vital staining and biopsies, chest radiographs, oropharyngeal examination, and indirect laryngoscopy. During prospective follow-up evaluation, cytology specimens were repetitively normal in 16 patients (57%), showed inflammatory changes in eight patients (29%), persisted as dysplasia in two patients (7%) (both had endoscopic and histologic evidence of esophagitis), and progressed to carcinoma in two patients (7%) (one esophageal, one laryngeal). Although histologic findings concurred with the resolution of dysplasia, biopsy specimens were characterized by a similar difficulty in distinguishing dysplasia from inflammation. Erroneous histologic diagnoses of carcinoma in situ were made in two patients with reflux esophagitis evident endoscopically and confirmed during the course of a 24-36 month follow-up period. The authors conclude that squamous cell dysplasia detected by balloon-mesh cytology is seldom a precursor of esophageal cancer in the high-risk U.S. population but, rather, is often related to esophagitis. Thus, balloon-mesh cytology has limited use as a screening method for the early detection of esophageal cancer in the United States.

Gastroesophageal reflux disease. Scintigraphic, endoscopic, and histologic considerations.

Radionucleotide scintigraphy and esophagoscopy with biopsy were carried out in 101 patients with symptoms strongly suggestive of gastroesophageal reflux (GER) disease. GER was visualized by scintigraphy in 86.1% of the patients. Endoscopic and histologic esophagitis were found in 68.1% and 58.4% patients, respectively, whereas both examinations taken together showed evidence of esophagitis in 82%. Histologic evidence of esophagitis was found in nearly all patients with severe endoscopic changes and in 43.7% patients with no endoscopic abnormality. Scintigraphic reflux was demonstrated more frequently (p less than 0.05) in the patients with severe endoscopic esophagitis (97.5%) than in those with no or only mild endoscopic changes (78.6%). Scintigraphic reflux was found in 91.5% and 78.5% of the patients with and without histologic evidence of esophagitis (p = 0.07). Fifteen of the 18 patients (83.3%) without endoscopic and histologic abnormalities in the esophagus had scintigraphic evidence of reflux. The present study strongly supports the clinical significance of scintigraphy in GER disease and confirms that esophageal biopsy specimens increase the sensitivity of endoscopic evaluation.

Properly conducted fundoplication reverses histologic evidence of esophagitis.

Little is known about the fate of histologic changes of esophagitis following an antireflux procedure. In a widely quoted paper (Gastroenterology 1979; 76:1393), initial healing of esophagitis was reported, but it was noted that normal biopsies reversed to abnormal in a small number of patients who were followed for up to 69 months. The authors studied esophageal histology in 21 patients undergoing a Nissen fundoplication by a standardized technique. All patients underwent biopsy after operation from 5 to 96 months (mean, 39 months). Nineteen of 21 patients had esophagitis typified by leukocytic infiltration shown on preoperative biopsy. Only two patients had these changes after operation, and one subsequently returned to normal. No patient had evidence of worsening of his esophageal mucosa over time, but several persisted with epithelial changes that included basal cell hyperplasia and papillary elevation. The authors conclude that the Nissen fundoplication, when performed by a standardized technique, leads to reversal of histologic evidence of esophagitis, even for follow-up periods of 96 months, and that the symptomatic status of a patient correlates well with the histologic level of esophagitis.