Trends in Esophageal Cancer Mortality and Stage at Diagnosis by Race and Ethnicity in the United States.

INTRODUCTION: Esophageal cancer (EC) is an aggressive malignancy with poor prognosis. Mortality and disease stage at diagnosis are important indicators of improvements in cancer prevention and control. We examined United States trends in esophageal adenocarcinoma (EAC) and esophageal squamous cell carcinoma (ESCC) mortality and stage at diagnosis by race and ethnicity. METHODS: We used Surveillance, Epidemiology, and End Results (SEER) data to identify individuals with histologically confirmed EAC and ESCC between 1 January 1992 and 31 December 2016. For both EAC and ESCC, we calculated age-adjusted mortality and the proportion presenting at each stage by race/ethnicity, sex, and year. We then calculated the annual percent change (APC) in each indicator by race/ethnicity and examined changes over time. RESULTS: The study included 19,257 EAC cases and 15,162 ESCC cases. EAC mortality increased significantly overall and in non-Hispanic Whites from 1993 to 2012 and from 1993 to 2010, respectively. EAC mortality continued to rise among non-Hispanic Blacks (NHB) (APC = 1.60, p = 0.01). NHB experienced the fastest decline in ESCC mortality (APC = - 4.53, p < 0.001) yet maintained the highest mortality at the end of the study period. Proportions of late stage disease increased overall by 18.5 and 24.5 percentage points for EAC and ESCC respectively; trends varied by race/ethnicity. CONCLUSION: We found notable differences in trends in EAC and ESCC mortality and stage at diagnosis by race/ethnicity. Stage migration resulting from improvements in diagnosis and treatment may partially explain recent trends in disease stage at diagnosis. Future efforts should identify factors driving current esophageal cancer disparities.

Endoscopic Therapies for Gastroparesis.

PURPOSE OF REVIEW: Gastroparesis remains a difficult-to-treat disease with limited therapeutic options. Though patients often have a common syndrome of stereotypic symptoms, the underlying pathophysiology is heterogeneous, often leading to variable treatment responses. Due to limitations in medical and surgical therapies, endoscopic options have been increasingly explored. These options can be broadly categorized into pyloric-directed therapy, non-pyloric-directed therapy, and nutritional support. In this review, we will highlight current and emerging endoscopic options, such as gastric per-oral endoscopic myotomy (G-POEM). RECENT FINDINGS: Early retrospective studies on G-POEM offer encouraging results up to one year out, with an acceptable safety profile. Other pyloric-directed therapies, such as pyloric dilation and stenting, have also been explored. While emerging endoscopic therapeutic options are encouraging, efficacy will likely depend on a better characterization of underlying pathophysiology and improved patient selection. Future prospective, controlled studies are needed.

For patients with primary achalasia the clinical success of pneumatic balloon dilatation can be predicted from the residual fraction of radionuclide during esophageal transit scintigraphy.

BACKGROUND: Esophageal transit scintigraphy (ETS) and esophagography have long been used to evaluate patients with achalasia. The objectives of our study were to evaluate the efficacy of endoscopic pneumatic dilatation (EPD) as treatment for Koreans with achalasia and to determine which findings from ETS and esophagography predict successful treatment of achalasia. METHODS: Patients with achalasia who were treated by EPD between April 2002 and January 2012 were recruited. We defined the success of EPD as 6 months or more of clinical remission without symptoms or a decrease in the Eckardt scores by at least two points and a total Eckardt score not exceeding 3. We reviewed the percentage of maximum scintigraphic activity retained in the esophagus at 30 s (R 30) and the post-PD rate of reduction of R 30 ((Pre R 30 - Post R 30)/Pre R 30 × 100) by ETS. Possible predictive factors determined by ETS and esophagography were analyzed. RESULTS: Our study included 53 eligible patients. The median symptom score (Eckardt score) was 5 (4-8). R 30 and T 1/2 were, respectively, 61.8 % and 38.5 min before EPD and 20 % and 4.19 min after EPD. Successful EPD was achieved for 40 of 53 (75.47 %) patients. Age (≥40, p = 0.027) and post-PD rate of reduction of R 30 (>20 %, p = 0.003) were best prognostic indicators of clinical success. There were no perforations related to EPD. CONCLUSION: Older age and a post-PD rate of reduction of R 30 were strongly associated with better outcomes. Examination with ETS before and after EPD can be used to objectively assess a patient's short-term response to EPD.

Severity of dyspeptic symptoms correlates with delayed and early variables of gastric emptying.

BACKGROUND: A simplified report of gastric retention values at select times is now recommended for scintigraphic gastric emptying test (GET). AIMS: The purpose of this study was to assess correlation between severity of gastroparetic symptoms and all variables of GET, compared to select variables in clinical use. METHODS: This was a prospective study of patients referred for scintigraphic GET. The Gastroparesis Cardinal Symptom Index questionnaire was obtained prior to the scintigraphy. Variables determined were lag time, half emptying time (T1/2), retention at 30 min, 1, 2 and 4 h. Statistical analysis was by Spearman rank correlation and Wilcoxon rank test with a significance set at p ≤ 0.05. RESULTS: Seven hundred seventeen patients had GET from 03/09 to 03/11. Results are from 325 patients who did not take medications known to affect GET were analyzed (64.9 % females, mean age 47 ± 18.9 years, 21.8 % diabetics, 78.2 % non-diabetic, of which 7.6 % were post-surgical, primarily post-fundoplication). Combined gastric retention at 2 and 4 h detected delayed GET in 83.5 % non-diabetics and 76.6 % of diabetics. Rapid GET was present in 11 % of patients at 30 min and 4 % at 1 h. Significant positive correlation was observed between nausea, vomiting, loss of appetite and variables of GET, but not with the half-time of emptying (T1/2). Bloating negatively correlated with retention at 2 h. There was no association between duration of symptoms and GET variables. CONCLUSIONS: Gastroparetic symptoms correlate with different retention times of GET, but not with T1/2. However, symptoms poorly distinguish between categories of gastroparesis or status of gastric emptying. Delayed GE is best detected by 2 and 4 h retention times, while 30 min and 1 h retention times detect rapid GE.

Topical bethanechol for the improvement of esophageal dysmotility: a pilot study.

OBJECTIVES: We studied a case series to evaluate the effect of topical bethanechol chloride on esophageal function in individuals with ineffective esophageal motility. METHODS: Five subjects with ineffective esophageal motility underwent high resolution esophageal manometry. Ten 5 mL liquid swallows were performed to establish a baseline. Five milligrams of topical bethanechol was then administered. After 10 minutes, the subjects completed 10 additional liquid swallows. This procedure was repeated with 10 mg of bethanechol in 4 subjects. RESULTS: After administration of 5 mg of topical bethanechol, the mean (+/- SD) distal contractile integral, an index of esophageal contractility, increased from 178.3 +/- 83.1 mm Hg x s x cm to 272.3 +/- 216.9 mm Hg x s x cm (p = 0.69). The percentage of failed swallows decreased from 52.8% +/- 33.2% to 29.4% +/- 18.3% (p = 0.14). The percentage of peristaltic swallows increased from 28.0% +/- 26.8% to 67.2% +/- 15.3% (p = 0.04). The contractile front velocity was essentially unchanged. After administration of 10 mg of bethanechol,the distal contractile integral decreased from 349.3 +/- 371.0 mm Hg x s x cm to 261.8 +/- 293.5 mm Hg x s x cm (p = 0.72). The percentage of failed swallows increased from 57.5% +/- 37.7% to 66.8% +/- 24.9% (p = 0.46). The percentage of peristaltic swallows increased from 17.5% +/- 23.6% to 28.3% +/- 19.1% (p = 0.29). The contractile front velocity decreased from 11.6 +/- 5.2 cm/s to 4.9 +/- 3.0 cm/s (p = 0.32). No adverse side effects occurred. CONCLUSIONS: The results of this pilot study support the need for further investigation with larger sample sizes and dose escalation.

A Comparative Assessment of the Diagnosis of Swallowing Impairment and Gastroesophageal Reflux in Canines and Humans.

Swallowing impairment is a highly prevalent and clinically significant problem affecting people and dogs. There are myriad causes of swallowing impairment of which gastroesophageal reflux is the most common in both species. Similarities in anatomy and physiology between humans and canines results in analogous swallowing disorders including cricopharyngeus muscle achalasia, esophageal achalasia, hiatal herniation, and gastroesophageal reflux with secondary esophagitis and esophageal dysmotility. Accordingly, the diagnostic approach to human and canine patients with swallowing impairment is similar. Diagnostic procedures such as swallowing fluoroscopy, high-resolution manometry, pH/impedance monitoring, and endolumenal functional luminal imaging probe can be performed in both species; however, nasofacial conformation, increased esophageal length, and the difficulty of completing several of these procedures in awake dogs are inherent challenges that need to be considered. Human patients can convey their symptoms and respond to verbal cues, whereas veterinarians must rely on clinical histories narrated by pet owners followed by comprehensive physical examination and observation of the animal eating different food consistencies and drinking water. Dogs may also be unwilling to drink or eat in the hospital setting and may be resistant to physical restraint during diagnostic procedures. Despite the species differences and diagnostic challenges, dogs are a natural animal model for many oropharyngeal and esophageal disorders affecting people, which presents a tremendous opportunity for shared learnings. This manuscript reviews the comparative aspects of esophageal anatomy and physiology between humans and canines, summarizes the diagnostic assessment of swallowing impairment in both species, and discusses future considerations for collaborative medicine and translational research.

Importance of diarrhea in evaluating constipation in irritable bowel syndrome clinical studies.

BACKGROUND: Irritable bowel syndrome (IBS) is a chronic functional gastrointestinal disorder characterized by alterations in bowel function, abdominal discomfort, and bloating. The symptoms of IBS vary widely between constipation and diarrhea predominance. In this study, we examine "constipation minus diarrhea" score (C-D) to account for the contribution of diarrhea and to create a reliable method for predicting constipation predominance in IBS. METHODS: A nested study was conducted in participants with IBS by Rome I criteria. After consent, they completed a daily stool diary for 1 week. This included recording frequency of bowel movements and describing consistency of stool using the Bristol stool scale. After submitting their diaries, participants rated their bowel symptoms using a visual analog score (VAS) scale from 0 to 100 mm, with 100 mm representing maximum severity. VAS scores for C, D, and C-D were subsequently compared with the true stool events of the previous week by stool diary to validate the potential usefulness of the simple C-D method. RESULTS: Eighty-four participants with IBS completed stool diaries and VAS surveys for bowel symptoms, from which C-D scores were compiled. By correcting for the predominance of constipation compared with diarrhea, C-D scores predicted constipation based on the frequency of bowel movements and Bristol stool score. Furthermore, a second method was used to validate the C-D technique by comparing the mean C-D score in participants with constipation (≤3 d with bowel movement in previous week). In this case, the mean C-D score was 74.1 ± 3.8 compared with -3.0 ± 5.9 for patients with >3 days with bowel movement in that week (P<0.001). Although the constipation severity alone also distinguished these 2 groups, the difference was less impressive (P<0.01). In participants with mean Bristol stool scores of ≤2 in the preceding week, the C-D mean score was 25.4 ± 6.1 compared with participants having mean Bristol stool score of >2 where the C-D was -11.1 ± 5.9 (P<0.01). Using constipation severity by VAS alone, there was no significant difference between these same 2 Bristol stool categories (P=0.29). CONCLUSIONS: IBS patients' self-assessment of constipation and diarrhea severity using the C-D score is an effective predictor of C-IBS and constipation severity. The C-D score may be a useful tool in future IBS constipation trials, as it seems to predict constipation and it correlates well with stool diaries.

Apple sauce improves detection of esophageal motor dysfunction during high-resolution manometry evaluation of dysphagia.

BACKGROUND: Esophageal manometry utilizes water swallows to evaluate esophageal motor abnormalities in patients with dysphagia, chest pain, or reflux symptoms. Although manometry is the gold standard for evaluation of these symptoms, patients with dysphagia often have normal results in manometry studies. AIM: The objective of this work was to test the hypothesis that challenging the esophagus with viscous apple sauce boluses uncovers motor abnormalities in patients with dysphagia not seen when using water swallows. METHODS: High-resolution esophageal manometry was performed using ten water swallows followed by ten apple sauce swallows in consecutive subjects presenting with dysphagia. Subjects with grossly abnormal water swallow evaluations were excluded. Each swallow was categorized as normal, hypotensive (distal isobaric contour plots of < 30 mmHg over >5 cm), or simultaneous (distal esophageal velocity ≥ 8.0 cm/s). Ineffective esophageal motility (IEM) was defined as ≥ 30% hypotensive swallows, and pressurization was defined as ≥ 20% simultaneous pressure waves. RESULTS: Data from 41 subjects was evaluated. Overall, 96.3% of water swallows were normal, 2.9% hypotensive, and 0.7% simultaneous. Only 70.3% of viscous swallows were normal; 16.7% were hypotensive and 13.0% were simultaneous (P < 0.001 all groups). Seven (17.1%) met criteria for IEM, and pressurization with viscous swallows was observed for nine (22.0%). Fourteen subjects (34.1%) had abnormal results from viscous studies. The presence of any abnormal water swallows was predictive of abnormal viscous swallows (OR = 9.00, CI = 2.15-80.0), although the presence of hypotensive or simultaneous water swallows was not associated with IEM (OR = 0.63, CI = 0.16-2.17) or pressurization (OR = 7.00, CI = 0.90-315.4) with viscous apple sauce. CONCLUSIONS: Apple sauce challenge increased identification of classifiable motor disorders in patients with dysphagia and may be preferred to alternative bolus materials.

Antibiotic prophylaxis prevents the development of a post-infectious phenotype in a new rat model of post-infectious IBS.

BACKGROUND: A recent post-infectious rat model with Campylobacter jejuni 81-176 has replicated the events noted in humans with post-infectious irritable bowel syndrome (IBS). In this study, we test whether prophylactic treatment with the antibiotic rifaximin will prevent the development of long-term altered bowel function in this model. METHODS: Sprague-Dawley rats were divided into two groups. Both groups were gavaged with a 1 mL solution of 10(8) cfu/mL of C. jejuni. However, one group was also prophylactically gavaged with a solution of rifaximin 200 mg per day for 3 days (the day before gavage, the day of gavage, and the day after gavage with C. jejuni). Fresh stool was collected from rats daily until two consecutive stool cultures were negative for C. jejuni. The rats were then housed for 3 months. At the end of 3 months, fresh stool was collected on three consecutive days to determine stool % wet weight and stool consistency on a stool score. RESULTS: Rats that received rifaximin antibiotic prophylaxis had a greater rate of stool shedding of C. jejuni. However, the mean duration of colonization was shorter in the rifaximin-treated group (10.3 ± 7.1 days) compared to rats receiving no prophylaxis (12.6 ± 5.9 days) (P < 0.01). After 3 months, rats that did not receive rifaximin had a greater variability in stool % wet weight (P < 0.01). Furthermore, the average stool consistency over 3 days of measurement was closer to normal in the rifaximin-treated rats, with a consistency of 1.1 ± 0.3, compared to 1.5 ± 0.4 in rats receiving no prophylaxis (P < 0.00001). CONCLUSIONS: Prophylactic treatment of rats with the antibiotic rifaximin in a new animal model of post-infectious IBS with C. jejuni mitigated the development of long-term altered stool form and function.

Acute and chronic histological changes of the small bowel secondary to C. jejuni infection in a rat model for post-infectious IBS.

BACKGROUND: Campylobacter jejuni has been implicated in the pathogenesis of post-infectious irritable bowel syndrome (PI-IBS) in humans, effects which may be because of cytolethal distending toxin (CDT). In this study, we characterized both acute and chronic-phase histological changes of the small bowel in rats exposed to wild-type C. jejuni 81-176, or a strain that does not produce CDT, by using a validated rat model of PI-IBS. METHODS: Sprague-Dawley rats were given 1.0 × 10(8) CFU of either wild-type C. jejuni 81-176 (C+, PI/C+) or the CDT-negative strain (CDT-), or vehicle alone (Control). Acute-phase rats (C+, CDT-) were euthanized on days 2, 4, 8, 16, and 32. Chronic-phase rats (PI/C+, Control) were euthanized 3 months after clearing the initial infection. Segments of duodenum, jejunum, and ileum were resected and the contents plated for C. jejuni culture, and tissue sections were stained for histology. RESULTS: We observed preferential infection of the ileum and jejunum by Campylobacter jejuni. Compared with controls, epithelial cell basal membrane ballooning, villous tip disruption, and reduced villous-to-crypt ratios were observed for both C+ and CDT- rats. Villous widening, the only result significantly different in C+ vs. CDT- rats, was greatest at day 4 (134.1 ± 21.12 µm vs. 109.9 ± 10.6 µm for CDT-, P < 0.01). Little or no cellular inflammatory changes were seen during acute C. jejuni infection. Three months after clearing the initial infection, no histological changes remained. CONCLUSION: Significant histological changes, with the absence of inflammatory cells, are seen in the duodenum, jejunum, and ileum of rats during acute infection with C. jejuni. These changes occurred irrespective of the presence or absence of the CDT toxin.

New clinical method for distinguishing D-IBS from other gastrointestinal conditions causing diarrhea: the LA/IBS diagnostic strategy.

Modern methods of diagnosing diarrhea-predominant irritable bowel syndrome (D-IBS) require a "diagnosis of exclusion" approach. In this study we aim to test the diagnostic ability of using the fluctuation of frequency and consistency of bowel patterns in IBS to discriminate it from other causes of diarrhea. Eligible subjects were asked to complete a questionnaire on the changes in form and frequency of bowel habits by time. The primary endpoint was to evaluate the diagnostic effectiveness of having irregularly irregular bowel function and form as more characteristic of IBS versus non-IBS causes. Patients were prospectively recruited from a tertiary care GI clinic. Subjects had to have diarrhea as their primary complaint. In the case of IBS, D-IBS subjects were recruited. Subjects with celiac disease, Crohn's and ulcerative colitis were recruited for comparison and were categorically called "non-IBS." Non-IBS subjects could not have a recent history of blood in stool or a history of bowel surgery, fistulae or narcotic use. Sixty-two IBS and 37 non-IBS subjects were recruited. Among the 62 IBS subjects, 49 (79%) stated that their bowel habits varied in form and frequency on a daily basis compared to 35% in non-IBS subjects (OR = 8.9, CI = 3.5-22.5, P < 0.00001). When subjects were compared by the number of different stool forms they had witnessed in the prior week, IBS subjects noted 3.58 +/- 0.19 types and non-IBS reported 2.35 +/- 0.16 (P < 0.00001). Using > or = 3 stool forms per week as a method of discriminating IBS from non-IBS, 50 out of 62 subjects with IBS (81%) reported this greater number of forms compared to 15 out of 37 (41%) non-IBS subjects (sensitivity = 0.81; specificity = 0.60). The use of this simple tool that identifies an irregularly irregular bowel form and function is successful in separating D-IBS from non-IBS subjects.

A high-resolution view of achalasia.

BACKGROUND: High-resolution manometry (HRM) makes it possible to better evaluate spatial and temporal characteristics of esophageal motor function. This technology is revealing new observations regarding disordered motor function in esophageal diseases. GOAL: The aim of this study was to define the essential features of achalasia using HRM. STUDY: We performed HRM on 27 patients with achalasia, 10 patients with gastroesophageal reflux disease, and 10 controls. Ten 5 mL water swallows were recorded with a solid-state manometric assembly incorporating 36 circumferential sensors spaced at 1-cm intervals. RESULTS: The resting lower esophageal sphincter pressure was greater in achalasia than in controls or gastroesophageal reflux disease. There was an absence of peristalsis in the smooth muscle esophagus and failure of lower esophageal sphincter relaxation. The resting upper esophageal sphincter pressure was not different among the 3 groups. In addition to the typical manometric findings of achalasia, new observations are included. Esophageal shortening, pressurization of the esophagus, and rhythmic contractions of the upper esophageal sphincter and striated muscle esophagus were frequently observed. CONCLUSIONS: HRM demonstrates alterations of esophageal motor function in achalasia that are not easily observed with other manometric techniques.

Concurrent findings of achalasia and duodenal duplication in a Down syndrome patient.

The association between Down syndrome and gastrointestinal anomalies such as duodenal and esophageal atresia, tracheoesophageal fistulas, and Hirschsprung's disease is well documented. More recently, an association between Down syndrome and achalasia was reported. In this report, we describe a 48-year-old woman with a history of Down syndrome who presented with dysphagia. Work-up of the dysphagia showed not only achalasia but also a duodenal duplication. To our knowledge, there have been no reports of Down syndrome associated with duodenal duplication. Whether this finding is simply a coincidence or whether duodenal duplication is associated with Down syndrome will need to be determined with future studies.

Clinical Characteristics of Patients with Untreated Achalasia.

BACKGROUND/AIMS: Patients with untreated achalasia frequently complain of heartburn and regurgitation. The diagnosis of achalasia might be delayed because these symptoms are misinterpreted as gastroesophageal reflux. We aim to evaluate the clinical, radiologic, and manometric findings in patient with untreated achalasia. METHODS: The records of patients diagnosed with primary achalasia between July 2004 and January 2012 at Gangnam Severance Hospital, Seoul, Korea were evaluated. We reviewed their clinical history and the findings of barium esophagogram, upper gastrointestinal endoscopy, and esophageal transit scintigraphy. We also compared the clinical, radiologic, and manometric findings of patients according to heartburn symptoms and proton pump inhibitor use. RESULTS: Our study included a total of 64 patients with a median age of 44.5 (interquartile range, 31.5-54.0). The median duration of symptoms was 23.5 (interquartile range, 5.3-57.0) months. Sixty-four patients (100%) had dysphagia, 49 (76.6%) had regurgitation, 35 (54.7%) had chest pain, and 38 (59.4%) had heartburn. Typical clinical features of gastroesophageal reflux disease (GERD) such as regurgitation, heartburn, and chest pain were observed in more than 50% of achalasia patients. Proton pump inhibitors were prescribed for 16 patients (25%) on the assumption that they had GERD. Patients with heartburn were more likely to experience weight loss (P = 0.009), regurgitation (P = 0.001), or chest pain (P = 0.019). CONCLUSIONS: Heartburn, regurgitation, and chest pain were commonly observed in patients with untreated achalasia. Therefore, these findings suggest that achalasia should be suspected in patients with refractory GERD.

Generation of nitric oxide in the opossum lower esophageal sphincter during physiological experimentation.

Lipopolysaccharide (LPS), given in vivo, modulates opossum esophageal motor functions by inducing the inducible nitric oxide synthase (iNOS), which increases nitric oxide (NO) production. Superoxide, a NO scavenger, is generated during this endotoxemia. Superoxide is cleared by superoxide dismutase (SOD) and catalase (CAT) to protect the physiological function of NO. This study examined whether lower esophageal sphincter (LES) motility, NO release, and iNOS and nitrotyrosine accumulation in the LES are affected by LPS in vitro. Muscle strips from the opossum LES were placed in tissue baths containing oxygenated Krebs buffer. NO release was measured with a chemiluminescence NOx analyzer, and Western blots were performed to analyze iNOS and nitrotyrosine production. The percent change in resting LES tone after a 6-hour exposure to LPS was significantly increased compared to pretreatment values. The percent LES relaxation upon electrical stimulation was significantly decreased in the control group at 6 hours, indicating that the LPS treatment had an effect. The NO concentration in the tissue bath of LPS- treated muscle without nerve stimulation was significantly less than that of LPS treatment combined with SOD/CAT or SOD/CAT alone. iNOS and nitrotyrosine were detectable and increased over time in the LES muscle of both the control and LPS-treated groups. Antioxidant enzymes may play a role in regulating NO-mediated neuromuscular functions in the LES.

High-resolution manometric evaluation of the effects of cisapride on the esophagus during administration of solid and liquid boluses in awake healthy dogs.

OBJECTIVE To validate the use of high-resolution manometry (HRM) in awake, healthy dogs and compare the effects of bolus type (liquid vs solid) and drug treatment (saline [0.9% NaCl] solution [SS] vs cisapride) on esophageal pressure profiles. ANIMALS 8 healthy dogs. PROCEDURES In a crossover study, each dog received SS (10 mL) IV, and HRM was performed during oral administration of 10 boluses (5 mL each) of water or 10 boluses (5 g each) of canned food. Cisapride (1 mg/kg in 60 mL of SS) was subsequently administered IV to 7 dogs; HRM and bolus administration procedures were repeated. Two to 4 weeks later, HRM was repeated following administration of SS and water and food boluses in 4 dogs. Pressure profile data were obtained for all swallows, and 11 outcome variables were statistically analyzed. RESULTS After SS administration, predicted means for the esophageal contractile integral were 850.4 cm/mm Hg/s for food boluses and 660.3 cm/mm Hg/s for water boluses. Predicted means for esophageal contraction front velocity were 6.2 cm/s for water boluses and 5.6 cm/s for food boluses after SS administration. Predicted means for residual LES pressure were significantly higher following cisapride administration. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that HRM was feasible and repeatable in awake healthy dogs of various breeds and sizes. Stronger esophageal contractions and faster esophageal contraction velocity occurred during solid bolus and liquid bolus swallows, respectively. Lower esophageal sphincter pressure increased significantly following cisapride administration. Esophageal contractions and bolus transit latency should be further evaluated by HRM in clinically dysphagic dogs.

Association of Systemic Sclerosis With a Unique Colonic Microbial Consortium.

OBJECTIVE: To compare colonic microbial composition in systemic sclerosis (SSc) patients and healthy controls and to determine whether certain microbial genera are associated with gastrointestinal (GI) tract symptoms in patients with SSc. METHODS: Healthy controls were age- and sex-matched (1:1) with adult SSc patients. Cecum and sigmoid mucosal lavage samples were obtained during colonoscopy. The microbiota in these samples were determined by Illumina HiSeq 2000 16S sequencing, and operational taxonomic units were selected. Linear discriminant analysis effect size was used to identify the genera that showed differential expression in SSc patients versus controls. Differential expression analysis for sequence count data was used to identify specific genera associated with GI tract symptoms. RESULTS: Among 17 patients with SSc (88% female; median age 52.1 years), the mean ± SD total GI Tract 2.0 score was 0.7 ± 0.6. Principal coordinate analysis illustrated significant differences in microbial communities in the cecum and sigmoid regions in SSc patients versus healthy controls (both P = 0.001). Similar to the findings in inflammatory disease states, SSc patients had decreased levels of commensal bacteria, such as Faecalibacterium and Clostridium, and increased levels of pathobiont bacteria, such as Fusobacterium and γ-Proteobacteria, compared with healthy controls. Bifidobacterium and Lactobacillus, which are typically reduced under conditions of inflammation, were also increased in abundance in patients with SSc. In SSc patients with moderate/severe GI tract symptoms, the abundance of Bacteroides fragilis was decreased, and that of Fusobacterium was increased, compared with patients who had no or mild symptoms. CONCLUSION: This study demonstrates a distinct colonic microbial signature in SSc patients compared with healthy controls. This unique ecologic change may perpetuate immunologic aberrations and contribute to clinical manifestations of SSc.

Lung Transplant Outcomes in Systemic Sclerosis with Significant Esophageal Dysfunction. A Comprehensive Single-Center Experience.

RATIONALE: Consideration of lung transplantation in patients with systemic sclerosis (SSc) remains guarded, often due to the concern for esophageal dysfunction and the associated potential for allograft injury and suboptimal post-lung transplantation outcomes. OBJECTIVES: The purpose of this study was to systematically report our single-center experience regarding lung transplantation in the setting of SSc, with a particular focus on esophageal dysfunction. METHODS: We retrospectively reviewed all lung transplants at our center from January 1, 2000 through August 31, 2012 (n = 562), comparing the SSc group (n = 35) to the following lung transplant diagnostic subsets: all non-SSc (n = 527), non-SSc diffuse fibrotic lung disease (n = 264), and a non-SSc matched group (n = 109). We evaluated post-lung transplant outcomes, including survival, primary graft dysfunction, acute rejection, bronchiolitis obliterans syndrome, and microbiology of respiratory isolates. In addition, we defined severe esophageal dysfunction using esophageal manometry and esophageal morphometry criteria on the basis of chest computed tomography images. For patients with SSc referred for lung transplant but subsequently denied (n = 36), we queried the reason(s) for denial with respect to the concern for esophageal dysfunction. MEASUREMENTS AND MAIN RESULTS: The 1-, 3-, and 5-year post-lung transplant survival for SSc was 94, 77, and 70%, respectively, and similar to the other groups. The remaining post-lung transplant outcomes evaluated were also similar between SSc and the other groups. Approximately 60% of the SSc group had severe esophageal dysfunction. Pre-lung transplant chest computed tomography imaging demonstrated significantly abnormal esophageal morphometry for SSc when compared with the matched group. Importantly, esophageal dysfunction was the sole reason for lung transplant denial in a single case. CONCLUSIONS: Relative to other lung transplant indications, our SSc group experienced comparable survival, primary graft dysfunction, acute rejection, bronchiolitis obliterans syndrome, and microbiology of respiratory isolates, despite the high prevalence of severe esophageal dysfunction. Esophageal dysfunction rarely precluded active listing for lung transplantation.