The changing faces of eosinophilic esophagitis: the impact of consensus guidelines at the University of South Florida.

BACKGROUND AND AIMS: Prior to the consensus guideline conference in 2007, eosinophilic esophagitis (EoE) was uncommon dominated by the fibrostenotic phenotype, but over the past decade has become a common cause of dysphagia with more inflammatory phenotypes diagnosed. We assessed the impact of guideline definitions on the characteristics of EoE phenotypes over the past 26 years at our institution. METHODS: We reviewed the electronic health record of 75 consecutive patients meeting guideline definition EoE from 1/1988 to 5/2014. We separated groups based on 5-year intervals of diagnosis and phenotype. For continuous data, results were summarized as mean difference and standard deviation with 95 % confidence intervals. RESULTS: Five groups based on 5-year intervals of diagnosis were identified: group 1-1988-1993 (n = 7), group 2-1994-1999 (n = 7), group 3-2000-2005 (n = 4), group 4-2006-2011 (n = 35), and group 5-2012-2014 (n = 22). Prior to 2000, all patients were diagnosed with fibrostenotic EoE. After the initial 2007 guideline conference, inflammatory EoE has predominated with only one-third diagnosed with fibrostenotic EoE. Prior to 2011, only two were diagnosed with PPI-REE. In the last 3 years, 8 out of 22 patients (32 %) had PPI-REE. Overall, 8 out of 10 (80 %) PPI-REE were the inflammatory phenotype. When comparing pre- (n = 18) and post (n = 57)-consensus definitions, there was a significant difference between age of diagnosis (30.710.2 vs. 41.3 ± 14.3; p = 0.001), age of symptom onset (18.4 +/15.2 vs. 32.4 ± 15.5), and initial esophageal diameter (10.5 ± 2.7 vs. 14.3 ± 4.2; p < 0.0001), respectively. CONCLUSIONS: Fibrostenotic EoE has steadily decreased, and inflammatory EoE is now the most recognized form. Across our 26-year experience, there was a decrease in delay in diagnosis and severity of esophageal stricture. The pivotal change occurred around 2007 corresponding to the first EoE guideline emphasizing the impact and importance of early detection of disease.

The natural history of steroid-naïve eosinophilic esophagitis in adults treated with endoscopic dilation and proton pump inhibitor therapy over a mean duration of nearly 14 years.

BACKGROUND: Despite the vast focus of research in eosinophilic esophagitis (EoE), the natural history of untreated EoE remains undefined. Current expert consensus panels are calling for natural history studies to define long-term risks, adverse events, and progression of the disease. OBJECTIVE: To address the natural course and long-term adverse events of EoE. DESIGN: Retrospective, single-center study. SETTING: Tertiary-care center. A cohort of patients from the year 1988 initially diagnosed as having congenital esophageal stenosis who were later reclassified as having EoE. PATIENTS: Ninety-five patients, with 13 meeting entrance criteria for idiopathic EoE with follow-up >5 years. INTERVENTIONS: Anti-acids and esophageal dilation. MAIN OUTCOME MEASUREMENTS: Clinical response, adverse events, long-term clinical outcomes, and progression of disease. RESULTS: Thirteen patients (mean age at diagnosis 30.3 years, 10 male) were evaluated over a 13.6-year mean follow-up (range 5-24 years). All patients experienced daily dysphagia, with 12 presenting with food impactions. Patients were treated with esophageal dilation (64% Maloney, 34% Savary, 2.5% through-the-scope balloon) and daily anti-acids. Patients were initially treated with an average of 3.2 dilations over the first year (range 1-6) to achieve a luminal size of 15.8 mm (range 14-18 mm). They were maintained successfully with dilations every 2 years, on average, based on symptoms. Two patients not adhering to recommended dilation schedules experienced repeat impactions. One adverse event from a mucosal tear required hospitalization (1 of 157, 0.6%). Seven of 13 had Barrett's esophagus, average length 2.4 cm (range 1-4 cm), 3 on initial EGD and 4 identified over a mean duration of 9.4 years. No patient developed dysplasia or malignancy. LIMITATIONS: Retrospective, small sample. CONCLUSION: The course of EoE over a 13.6-year mean duration, although persistent, appears benign and not associated with cancer risk. A program of regular esophageal dilations based on symptom recurrence appears to be a safe, long-term treatment.

Eosinophilic esophagitis: a paradigm shift for pathology.

BACKGROUND: Eosinophilic esophagitis (EoE) is an increasingly recognized disease only reported in the adult literature since 1993. Our facility has the opportunity to evaluate steroid-naive EoE patients since 1988, allowing us to describe the evolution of the histologic diagnosis of EoE. METHODS: This retrospective study analyzed 95 patient charts with initial diagnosis of congenital esophageal stenosis/EoE from 1988 to 2012. Patients had dysphagia and met endoscopic criteria consistent with current EoE histologic criteria while on chronic proton-pump inhibitor therapy. Histologic slides were obtained for only 10 patients because of limited slide availability; and the slides were reviewed by a single pathologist. EoE is defined as ≥1 biopsy specimens demonstrating >15 eosinophils/HPF. RESULTS: Following review of histologic analysis reports, pathologists in our 2 academic hospitals began recognizing EoE as separate disease entity starting in 2007, coincidental with first EoE guidelines. After 2007, there was a clear surge in histologic diagnosis of EoE. Slides from 10 patients from 1988 to 2012 were reviewed. Of 35 biopsy sets, 19 were previously interpreted as reflux esophagitis (RE) or acute/chronic inflammation, 3 as RE with eosinophils, 2 as normal, and 11 as EoE. Reevaluation revealed EoE in 79% specimens with RE/inflammation and 100% with RE and eosinophils; remaining specimens had confirmed original diagnosis. All 10 patients had at least one set of slides meeting current EoE histologic criteria. CONCLUSIONS: EoE as a disease has been present for at least 2 to 3 decades. This is the first report of a clearly demarcated time point reflecting a paradigm shift in the histologic diagnosis of EoE as a distinct entity resulting from a seminal consensus report.

Endoscopic lumen restoration for obstructive aphagia: outcomes of a 25-year experience.

BACKGROUND: After chemoradiation therapy for head/neck cancer, some patients develop strictures that progress to complete pharyngoesophageal occlusion. Total lumen occlusion is less often due to other conditions. Enteral access (enterostomy tube) and good nutritional status tend to minimize the significance of dysphagia and therefore may mask recognition of impending complete lumen occlusion. OBJECTIVE: Review outcomes of a 25-year experience with endoscopic lumen restoration (ELR) in 30 patients. DESIGN: Retrospective, case review study. SETTING: Two tertiary-care referral centers. PATIENTS: This study involved 30 consecutive patients referred for obstructive aphagia due to complete lumen occlusion, primarily after chemoradiation therapy for head/neck cancer. INTERVENTION: Antegrade and retrograde endoscopy with tri-plane fluoroscopy for penetrating the occluded segment, serial retrograde and antegrade dilations, plus swallowing rehabilitation therapy. MAIN OUTCOME MEASUREMENTS: Restoration of lumen patency, swallowing function, and removal of enteral feeding tube. RESULTS: ELR was successful in 30 patients in 31 of 33 attempts (93%). Return to soft to regular diet was achieved in 15 of 30 patients (50%), and fluids to pureed food with partial percutaneous endoscopic gastrostomy nutrition was achieved in 5 of 30 patients (17%). Ten of 30 patients (33%) were considered unsafe for oral feeding because of oropharyngeal neuromotor deficits. Complications occurred in 5 of 30 patients (17%), with no prolonged sequelae, deaths, or surgery, but two stents were placed for anastomotic fistulas. The median duration of follow-up was 22.75 months. LIMITATIONS: Retrospective, case review study. CONCLUSION: ELR by using tri-plane fluoroscopic guidance with antegrade and retrograde endoscopy and serial dilations allows lumen restoration and swallowing to some degree in a majority of patients. Engagement of a core team of specialists can provide optimal restoration of swallowing function.

The normal anatomy around the oesophagogastric junction: an endoscopic view.

Where the oesophagus ends and the stomach begins has been a bone of contention for decades between the histologist, physiologist, gastroenterologist, radiologist and surgeon. The oesophagogastric junction (OGJ) is an important anatomical region because of its essential functions in relation to swallowing and as a site of structural defects, inflammation, metaplasia and neoplasia. The location of the diaphragmatic hiatus in relation to the distal oesophagus, the level of the squamocolumnar mucosal junction (SCJ), the location of the distal margin of the mucosal palisade veins and the proximal margin of the gastric mucosal folds are features that permit an accurate endoscopic diagnosis of hiatal hernia and reflux sequelae, including even a minimal extent for Barrett's oesophagus. The physiological OGJ region can be considered to be between the rosette of the lower oesophageal sphincter (LOS) and the angle of His. The most reliable benchmarks for the precise mural OGJ that can be identified during endoscopy are the levels of the cephalad margins of the linear gastric mucosal folds, viewed with the lumen deflated as much as possible, that are juxtaposed to the level of the caudad extent of the oesophageal mucosal palisade veins.

Esophagography predicts favorable outcomes after laparoscopic Nissen fundoplication for patients with esophageal dysmotility.

BACKGROUND: We undertook this study to determine if clearance of a food bolus at preoperative esophagography predicts acceptable outcomes after laparoscopic Nissen fundoplication for patients with manometrically abnormal esophageal motility. STUDY DESIGN: Patients with gastroesophageal reflux disease (GERD) or symptomatic hiatal hernia with evidence of esophageal dysmotility by stationary manometry underwent videoesophagography to document the ability of their esophagus to clear food boluses of varying consistencies. Sixty-six patients were identified who had manometric dysmotility yet were able to clear a food bolus at esophagography, and subsequently underwent laparoscopic Nissen fundoplication. These patients were compared with 100 randomly selected patients with normal motility who underwent laparoscopic Nissen fundoplication. Symptom reduction and satisfaction were assessed through followup. Patients with normal motility were compared with those with manometrically moderate and severe dysmotility. RESULTS: Preoperative patient demographic data, symptoms, and symptom scores were similar among patients with normal motility and moderate or severe dysmotility. After fundoplication, symptom reduction was notable for all patients regardless of preoperative motility (p < 0.01, paired Student's t-test). There was no notable difference in postoperative symptom scores (p = NS, Kruskal-Wallis ANOVA) or in patient satisfaction (p = NS, chi-square analysis) among patients stratified by esophageal motility. CONCLUSIONS: Patients with esophageal dysmotility documented by manometry who are able to clear a food bolus at contrast esophagography, have functional results after laparoscopic Nissen fundoplication similar to patients with normal motility. Preoperative esophagography predicts successful outcomes after laparoscopic Nissen fundoplication for patients with manometric esophageal dysmotility.

Sialorrhea: a review of a vexing, often unrecognized sign of oropharyngeal and esophageal disease.

Saliva is produced by the major salivary glands (parotid, submandibular, and sublingual), as well as several smaller glands. Salivary flow can be altered by multiple entities. There is much written regarding xerostomia ("dry mouth"), the condition related to inhibited or decreased salivary flow. This condition is widely recognized in certain systemic diseases, particularly Sjögren syndrome, diabetes mellitus, after anticholinergic, antihistamine, and decongestant medications, as well as states of enhanced sympathetic drive, such as anxiety or emotional disturbances and various other psychosocial conditions. On the other hand, sialorrhea or ptyalism, the condition of increased salivary flow, is rarely discussed in the clinical literature. Sialorrhea can occur with various neurologic disorders, infections, the secretory phase of the menstrual cycle, heavy metal poisoning, Wilson disease, Angelman syndrome, as well as a relatively unknown condition called idiopathic paroxysmal sialorrhea. Normal salivation may be altered by drugs (such as clozapine, risperidone, nitrazepam, lithium, and bethanecol) that have a cholinergic effect that induces sialorrhea. This report focuses on sialorrhea as it relates to disorders of the oropharynx and esophagus. The patient typically recognizes a problem with excessive "foamy mucus" but does not understand its origin. Infections and obstruction are the most common oropharyngeal causes. Increased salivary flow occurs as a typically subtle manifestation of gastroesophageal reflux disease. This occurrence is referred to as water brash. Idiopathic achalasia and megaesophagus due to the parasite Trypanosoma cruzi are regularly associated with sialorrhea. Esophageal obstruction (foreign body, cancer, or stricture formation), infection, and nasogastric intubation are the more common conditions associated with the symptomatic sequelae of sialorrhea. Sialorrhea-related respiratory and pulmonary complications are greatest in those with a diminished sensation of salivary flow and hypopharyngeal retention. Extremes of age, the chronically debilitated, or those in chronic care facilities, especially associated with cerebrovascular accidents and esophageal cancer, typically comprise this population. For the patient with an intact awareness of saliva, sialorrhea can present with significant social stigmas. Occult drooling or regular oral evacuation into a tissue or "spit cup" is socially incapacitating. This report provides a review of the physiology, pathogenesis, clinical manifestations, and therapeutic options for sialorrhea. Physicians and other healthcare professionals should recognize the importance of sialorrhea as a possible indicator or complication of a variety of disease states of the oropharynx and esophagus as well as its impact on the patient's physical and social quality of life.

Early results of laparoscopic Heller myotomy do not necessarily predict long-term outcome.

BACKGROUND: We sought to evaluate how patients' symptoms evolve after laparoscopic Heller myotomy. METHODS: Before and after laparoscopic Heller myotomy, 88 patients graded dysphagia and heartburn on a Likert scale (0 = none; 5 = severe). Patients graded outcomes as excellent, good, fair, or poor. Outcomes were compared in the same patients at 1 and 3 years of follow-up. RESULTS: At early follow-up (10.6 +/- 7.8 months) significant reductions were noted in dysphagia (11% versus 100%), dysphagia scores (0.6 +/- 1.1 versus 4.7 +/- 0.7), heartburn (31% versus 72%), and heartburn scores (1.2 +/- 1.6 versus 2.7 +/- 1.9). By late follow-up (37.6 months +/- 18.0) these values increased (47%, 1.9 +/- 1.7, 48%, 1.8 +/- 1.5, respectively) but remained significantly reduced compared with before operation. Excellent/good outcomes at early and late follow-up were 89% and 85%, respectively (P = not significant). CONCLUSIONS: Laparoscopic Heller myotomy is highly effective at palliating the symptoms of achalasia. With time, symptoms may recur owing to esophageal dysmotility, mandating continued surveillance.

Barrett esophagus: endoscopic findings and what to biopsy.

Barrett esophagus (BE) is considered the precursor for nearly all cases of esophageal adenocarcinoma. The potential sequence from intestinal metaplasia to dysplasia to cancer can best be monitored by careful endoscopic observation and surveillance biopsies. The ability to diagnose BE, biopsy accurately, and appropriately monitor are requisites for all who care for patients with this disorder. The normal endoscopic anatomy of the esophagogastric junction region and the changes that are associated with BE are discussed. The relationship of the squamocolumnar mucosal junction to the proximal margin of the gastric folds and the distal extent of the linear esophageal vessels is the principal landmark for diagnosis. Chromoendoscopy with methylene blue and Lugol iodine will enhance endoscopic observation, thereby allowing directed biopsies. Biopsy forceps and technique are reviewed along with the when and where for surveillance biopsies. Since most dysplasia and intramucosal cancer is focal and invisible to the endoscopist, it is easy to understand why the sampling error exceeds 95% using a standard four-quadrant biopsy protocol. Currently, this sampling error can be reduced by four-quadrant biopsies at closer intervals and biopsies of even the most minor focal abnormalities of mucosa in the BE segment. Screening may be enhanced in the future depending upon successful development of new cytologic, spectrographic, and tomographic methods capable of identifying foci of dysplasia or cancer that can be confirmed by targeted biopsies.

Preoperative intervention does not affect esophageal muscle histology or patient outcomes in patients undergoing laparoscopic Heller myotomy.

Botox injection and pneumatic dilation are common therapies for achalasia. We sought to determine the impact of these preoperative therapies on esophageal muscle histology and outcomes after laparoscopic Heller myotomy. A total of 73 consecutive patients had esophageal muscle biopsies taken from the gastroesophageal junction at the time of myotomy between November 1998 and November 2001. Muscle fibrosis was graded by a senior pathologist who was blinded to preoperative treatments and postoperative outcomes. Patients graded their dysphagia and heartburn symptoms before and after myotomy and graded their outcomes at follow-up. Patients were grouped according to the preoperative endoscopic treatment (dilation, Botox, both, or neither) and the groups were compared. Preoperative therapy did not correlate with esophageal fibrosis or postoperative outcomes, and the degree of esophageal muscle fibrosis was not predictive of outcome. Symptom scores improved significantly for dysphagia (4.5 +/- 0.9 vs. 1.6 +/- 1.6) and heartburn (2.3 +/- 1.8 vs. 1.5 +/- 1.4) irrespective of preoperative therapy or fibrosis. Overall, excellent or good outcomes were obtained in 92% of patients at follow-up of 15.7 months +/- 14.4. Successful outcomes are highly probable after laparoscopic Heller myotomy regardless of preoperative interventions. The amount of fibrosis in the esophageal muscle is not related to preoperative intervention and is not predictive of outcomes.

Visceral sensitivity in gastroesophageal reflux.

Symptomatic gastroesophageal reflux disease (GERD) is characterized by a wide spectrum of symptoms. The variance of GERD symptoms may be due to a decreased threshold for symptom elicitation/perception described as "visceral sensitivity." In this study GERD symptoms were scored for presence/frequency. The symptom score was weighted for the presence/frequency of typical reflux symptoms: heartburn, retrosternal pain, and regurgitation. The weighted GERD symptom score was used to assess symptom expansion and the hypothesis of GERD visceral sensitivity. One hundred five subjects with heartburn/retrosternal pain underwent esophageal pH studies. Subjects with abnormal esophageal pH studies reported more GERD-related symptoms, occurring more frequently, compared to subjects with normal esophageal pH studies. Symptom scores correlated with the number of reflux episodes but not with the length of time of mucosal exposure to acid. Therefore, aggregation of symptoms in gastroesophageal reflux is associated with frequent alternation between low and normal pH values in the distal esophagus.

The "learning curve" in videoscopic Heller myotomy.

OBJECTIVES: In the early 1990s, minimally invasive videoscopy was applied to numerous operations. After undertaking more than 50 "open" Heller myotomies, our experience with videoscopic Heller myotomy began in 1992. We sought to determine whether the outcome following videoscopic Heller myotomy is influenced by surgeon experience. METHODS: Seventy-eight patients with severe dysphagia secondary to achalasia underwent videoscopic Heller myotomy between 1992 and 1998. Intraoperative endoscopy was utilized to ensure adequate myotomy in all patients. Patients were stratified into 3 groups: the first 25 patients (group I), the second 25 patients (group II), and the last 28 patients (group III). Clinical outcome was based on length of stay, incidence of intraoperative complications, conversion to an 'open' procedure, and postoperative symptoms. RESULTS: Perioperative complications occurred in 20% of patients in group I compared with 8% and 12% in groups II and III, respectively (P = NS). Only 3 patients required conversion to an 'open' procedure, all in group I (P <0 .05). Symptomatic improvement was achieved in 80% of patients in group I, 100% in group II, and 96% in group III (P < 0.05). Significant reductions in conversions to open, length of stay, and postoperative symptoms were seen after 20 myotomies were undertaken. CONCLUSION: Outcome following videoscopic Heller myotomy, like other videoscopic operations, improves as surgeons progress along the videoscopic "learning curve." After approximately 20 videoscopic Heller myotomies, surgeons can expect fewer conversions to open procedures, shorter hospital stays, and better symptomatic relief.