Predictors of long-term clinical outcomes after TIPS: An ALTA group study.

BACKGROUND AND AIMS: While transjugular intrahepatic portosystemic shunt (TIPS) is traditionally considered a bridge to liver transplant (LT), some patients achieve long-term transplant-free survival (TFS) with TIPS alone. Prognosis and need for LT should not only be assessed at time of procedure, but also re-evaluated in patients with favorable early outcomes. APPROACH AND RESULTS: Adult TIPS recipients in the multicenter Advancing Liver Therapeutic Approaches retrospective cohort study were included (N=1,127 patients; 2,040 person-years follow-up). Adjusted competing risk regressions were used to assess factors associated with long-term post-TIPS clinical outcomes at time of procedure and at 6 months post-TIPS. MELD-Na at TIPS was significantly associated with post-TIPS mortality (sHR of death 1.1 [p=0.42], 1.3 [p=0.04], and 1.7 [p<0.01] for MELD-Na 15-19, 20-24, and ≥25 relative to MELD-Na <15, respectively). MELD 3.0 was also associated with post-TIPS outcomes. Among the 694 (62%) patients who achieved early (6 mo) post-TIPS TFS, rates of long-term TFS were 88% at 1-year and 57% at 3-years post-TIPS. Additionally, a within-individual increase in MELD-Na score of >3 points from TIPS to 6 months post-TIPS was significantly associated with long-term mortality, regardless of initial MELD-Na score (sHR of death 1.8, p<0.01). For patients with long-term post-TIPS TFS, rates of complications of the TIPS or portal hypertension were low. CONCLUSIONS: Among patients with early post-TIPS TFS, prognosis and need for LT should be reassessed, informed by post-procedure changes in MELD-Na and clinical status. For selected patients, "destination TIPS" without LT may offer long-term survival with freedom from portal hypertensive complications.

National survey of second opinions for hospitalized patients in need of liver transplantation.

Decisions about patient candidacy for liver transplant (LT) can mean the difference between life and death. We surveyed LT centers across the United States to assess their perceptions of and barriers to second-opinion referrals for inpatients declined for transplant. The medical and surgical directors of 100 unique US LT programs that had done >20 LTs in 2021 were surveyed with a 33-item questionnaire including both multiple-choice and free-response questions. The response rate was 60% (60 LT centers) and included 28 larger-volume ( ≥100 LTs in 2021) and 32 smaller-volume (<100 LTs in 2021) programs. The top 3 reasons for inpatient denial for LT included lack of social support (21%), physical frailty (20%), and inadequate remission duration from alcohol use (11%). Twenty-five percent of the programs reported "frequently" facilitating a second opinion for a declined inpatient, 52% of the programs reported "sometimes" doing so, and 7% of the programs reported never doing so. One hundred percent of the programs reported that they receive referrals for second opinions. Twenty-five percent of the programs reported transplanting these referrals frequently (over 20% of the time). Neither program size nor program location statistically impacted the findings. When asked if centers would be in favor of standardizing the evaluation process, 38% of centers would be in favor, 39% would be opposed, and 23% were unsure. The practices and perceptions of second opinions for hospitalized patients evaluated for LT varied widely across the United States. Opportunities exist to improve equity in LT but must consider maintaining individual program autonomy.

The role of gastrointestinal pathogen polymerase chain reaction testing in liver transplant recipients hospitalized with diarrhea.

BACKGROUND: Diarrhea is a common symptom among liver transplant (LT) recipients and can result in significant morbidity. The utility of PCR-based multiplex gastrointestinal (GI) pathogen panels in this population is unknown. METHODS: We assessed incidence, predictors, and outcomes of GI PCR positivity among inpatients who underwent stool pathogen testing with the FilmArray multiplex GI PCR panel at our institution within 1 year following LT from April 2015 to December 2019. RESULTS: A total of 112 patients were identified. Of these, 14 (12.5%) had a positive PCR for any pathogen. Escherichia coli (n = 9) and Norovirus (n = 5) were the most common pathogens detected. Recipients with a positive PCR were significantly further from LT (median 74.5 vs. 15.5 days, p < .01) and tested earlier during hospitalization (median 1.0 vs. 9.0 days, p < .01). C. difficile was positive in 20.0% of patients with a positive PCR and 11.4% with a negative PCR. CMV viremia was observed in 11.6% of patients, all in the negative PCR group. Following a positive PCR, patients were more likely to have a change in antimicrobial regimen (71.4% vs. 28.6%, p = .02), a shorter length of stay (median 7.5 vs. 17.5 days, p < .01), and a trend toward lower rates of readmission and colonoscopy within 30 days. CONCLUSIONS: In hospitalized LT recipients with diarrhea, GI PCR pathogen identification was associated with the use of targeted antimicrobial therapy and a shorter length of stay. GI PCR testing should be considered early during admission and later in the post-LT period.

Relationship Between Body Composition and Death in Patients with COVID-19 Differs Based on the Presence of Gastrointestinal Symptoms.

BACKGROUND: Patients with SARS-CoV-2 who present with gastrointestinal symptoms have a milder clinical course than those who do not. Risk factors for severe COVID-19 disease include increased adiposity and sarcopenia. AIMS: To determine whether body composition risk factors are associated with worse outcomes among patients with gastrointestinal symptoms. METHODS: This was a retrospective study of hospitalized patients with COVID-19 who underwent abdominal CT scan for clinical indications. Abdominal body composition measures including skeletal muscle index (SMI), intramuscular adipose tissue index (IMATI), visceral adipose tissue index (VATI), subcutaneous adipose tissue index (SATI), visceral-to-subcutaneous adipose tissue ratio (VAT/SAT ratio), and liver and spleen attenuation were collected. The association between body composition measurements and 30-day mortality was evaluated in patients with and without gastrointestinal symptoms at the time of positive SARS-CoV-2 test. RESULTS: Abdominal CT scans of 190 patients with COVID-19 were evaluated. Gastrointestinal symptoms including nausea, vomiting, diarrhea, or abdominal pain were present in 117 (62%). Among patients without gastrointestinal symptoms, those who died had greater IMATI (p = 0.049), less SMI (p = 0.010), and a trend toward a greater VAT/SAT ratio. Among patients with gastrointestinal symptoms, those who died had significantly greater IMATI (p = 0.025) but no differences in other measures. CONCLUSIONS: Among patients with COVID-19, those without gastrointestinal symptoms showed the expected associations between mortality and low SMI, high IMATI, and trend toward higher VAT/SAT ratio, but those with gastrointestinal symptoms did not. Future studies should explore the mechanisms for the altered disease course in patients with COVID-19 who present with gastrointestinal symptoms.

Body Mass Index and Risk for Intubation or Death in SARS-CoV-2 Infection : A Retrospective Cohort Study.

BACKGROUND: Obesity is a risk factor for pneumonia and acute respiratory distress syndrome. OBJECTIVE: To determine whether obesity is associated with intubation or death, inflammation, cardiac injury, or fibrinolysis in coronavirus disease 2019 (COVID-19). DESIGN: Retrospective cohort study. SETTING: A quaternary academic medical center and community hospital in New York City. PARTICIPANTS: 2466 adults hospitalized with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 infection over a 45-day period with at least 47 days of in-hospital observation. MEASUREMENTS: Body mass index (BMI), admission biomarkers of inflammation (C-reactive protein [CRP] level and erythrocyte sedimentation rate [ESR]), cardiac injury (troponin level), and fibrinolysis (D-dimer level). The primary end point was a composite of intubation or death in time-to-event analysis. RESULTS: Over a median hospital length of stay of 7 days (interquartile range, 3 to 14 days), 533 patients (22%) were intubated, 627 (25%) died, and 59 (2%) remained hospitalized. Compared with overweight patients, patients with obesity had higher risk for intubation or death, with the highest risk among those with class 3 obesity (hazard ratio, 1.6 [95% CI, 1.1 to 2.1]). This association was primarily observed among patients younger than 65 years and not in older patients (P for interaction by age = 0.042). Body mass index was not associated with admission levels of biomarkers of inflammation, cardiac injury, or fibrinolysis. LIMITATIONS: Body mass index was missing for 28% of patients. The primary analyses were conducted with multiple imputation for missing BMI. Upper bounding factor analysis suggested that the results are robust to possible selection bias. CONCLUSION: Obesity is associated with increased risk for intubation or death from COVID-19 in adults younger than 65 years, but not in adults aged 65 years or older. PRIMARY FUNDING SOURCE: National Institutes of Health.

The Distribution of Enteric Infections Utilizing Stool Microbial Polymerase Chain Reaction Testing in Clinical Practice.

BACKGROUND: Gastrointestinal infection is a major cause of morbidity. We sought to characterize the pathogenic etiologies of gastrointestinal infection to identify seasonal patterns and predictors of specific infections utilizing a multiplex PCR assay in clinical practice. METHODS: We performed a cross-sectional study of 9403 patients who underwent 13,231 stool tests with a FilmArray gastrointestinal pathogen PCR panel during an episode of diarrhea from March 2015 to May 2017. Our primary outcome was the presence of a positive panel. Logistic regression was used to test for associations between season and infections. RESULTS: A positive result was found in 3426 tests (25.9%) in 2988 patients (31.8%), yielding 4667 pathogens consisting of 1469 viruses (31.5%), 2925 bacteria (62.7%), and 273 parasites (5.8%). Age less than 50 years was associated with a higher prevalence of pathogens compared to age ≥ 50 (p < 0.0001). The overall prevalence of a positive result for bacteria peaked in the summer (635, 29.2%), and the prevalence of viruses peaked in the winter (446, 31.8%). Compared to the winter, testing in the summer yielded a higher prevalence of bacteria (OR 1.52, 95% CI 1.33, 1.73, p < 0.0001) and lower odds of viruses (OR 0.69, 95% CI 0.58, 0.81, p < 0.0001), primarily driven by E. coli species and norovirus. CONCLUSIONS: Season was a major determinant in detecting specific pathogens. Our substantially lower positivity rate than previous reports in the literature on multiplex PCR assays may more accurately reflect true clinical practice. Recognizing the temporal distribution of enteric pathogens may help facilitate empiric treatment decisions in certain clinical situations.

Stool PCR for Gastrointestinal Pathogens in Patients With and Without Immune-Mediated Intestinal Diseases.

BACKGROUND: Patients with celiac disease and inflammatory bowel disease, two immune-mediated luminal conditions, have higher rates of certain infections than healthy counterparts. The prevalence of many gastrointestinal infections in these patients, however, is unknown. AIMS: Using a novel clinical stool pathogen PCR test, we investigated the hypothesis that patients with celiac disease/inflammatory bowel disease had different distributions of diarrheal pathogens than other patients. METHODS: We performed a retrospective cohort study of outpatients who underwent stool pathogen testing with the FilmArray Gastrointestinal PCR Panel (BioFire Diagnostics, Salt Lake City, UT) at our institution from January 1 to December 31, 2015. Rates of pathogens were measured in patients with or without celiac disease/inflammatory bowel disease. RESULTS: Of 955 patients, 337 had positive test for any pathogen, with 465 bacterial, parasitic, or viral pathogens identified. One hundred and twenty-seven patients (13.3%) had celiac disease or inflammatory bowel disease, of which 29/127 (22.8%) had a positive test, compared to 308/828 other patients (37.2%) (p = 0.002). Patients with celiac disease/inflammatory bowel disease had significantly fewer viruses (1.6 vs. 8.1% of patients; p = 0.008) and parasites (0 vs. 3.3%; p = 0.039), with nonsignificant trend toward fewer bacteria (21.3 vs. 29.2%; p = 0.063). Escherichia coli species were most common in both populations. CONCLUSIONS: Stool PCR identified numerous pathogens in patients with or without celiac disease/inflammatory bowel disease. Patients with celiac disease/inflammatory bowel disease were significantly less likely to have any pathogen identified, and had significantly fewer viruses and parasites. In this population, knowledge of common pathogens can guide diagnostic evaluation and offer opportunities for treatment.

Risk of Clostridium difficile Infection in Patients With Celiac Disease: A Population-Based Study.

OBJECTIVES: Patients with celiac disease are at increased risk for infections such as tuberculosis, influenza, and pneumococcal pneumonia. However, little is known about the incidence of Clostridium difficile infection (CDI) in patients with celiac disease. METHODS: We identified patients with celiac disease based on intestinal biopsies submitted to all pathology departments in Sweden over a 39-year period (from July 1969 through February 2008). We compared risk of CDI (based on stratified Cox proportional hazards models) among patients with celiac disease vs. without celiac disease (controls) matched by age, sex, and calendar period. RESULTS: We identified 28,339 patients with celiac disease and 141,588 controls; neither group had a history of CDI. The incidence of CDI was 56/100,000 person-years among patients with celiac disease and 26/100,000 person-years among controls, yielding an overall hazard ratio (HR) of 2.01 (95% confidence interval (CI), 1.64-2.47; P<0.0001). The risk of CDI was highest in the first 12 months after diagnosis of celiac disease (HR, 5.20; 95% CI, 2.81-9.62; P<0.0001), but remained high, compared to that of controls, 1-5 years after diagnosis (HR, 1.85; 95% CI, 1.22-2.81; P=0.004). Among 493 patients with CDI, antibiotic data were available for 251; there were no significant differences in prior exposures to antibiotics between patients with celiac disease and controls. CONCLUSIONS: In a large population-based cohort study, patients with celiac disease had significantly higher incidence of CDI than controls. This finding is consistent with prior findings of higher rates of other infections in patients with celiac disease, and suggests the possibility of altered gut immunity and/or microbial composition in patients with celiac disease.

Racial and ethnic disparities in access to and utilization of living donor liver transplants.

Living donor liver transplantation (LDLT) is a comparable alternative to deceased donor liver transplantation and can mitigate the risk of dying while waiting for transplant. Although evidence exists of decreased utilization of living donor kidney transplants among racial minorities, little is known about access to LDLT among racial/ethnic minorities. We used Organ Procurement and Transplantation Network/United Network for Organ Sharing data from February 27, 2002 to June 4, 2014 from all adult liver transplant recipients at LDLT-capable transplant centers to evaluate differential utilization of LDLTs based on race/ethnicity. We then used data from 2 major urban transplant centers to analyze donor inquiries and donor rule-outs based on racial/ethnic determination. Nationally, of 35,401 total liver transplant recipients performed at a LDLT-performing transplant center, 2171 (6.1%) received a LDLT. In multivariate generalized estimating equation models, racial/ethnic minorities were significantly less likely to receive LDLTs when compared to white patients. For cholestatic liver disease, the odds ratios of receiving LDLT based on racial/ethnic group for African American, Hispanic, and Asian patients compared to white patients were 0.35 (95% CI, 0.20-0.60), 0.58 (95% CI, 0.34-0.99), and 0.11 (95% CI, 0.02-0.55), respectively. For noncholestatic liver disease, the odds ratios by racial/ethnic group were 0.53 (95% CI, 0.40-0.71), 0.78 (95% CI, 0.64-0.94), and 0.45 (95% CI, 0.33-0.60) respectively. Transplant center-specific data demonstrated that African American patients received fewer per-patient donation inquiries than white patients, whereas fewer African American potential donors were ruled out for obesity. In conclusion, racial/ethnic minorities receive a disproportionately low percentage of LDLTs, due in part to fewer initial inquiries by potential donors. This represents a major inequality in access to a vital health care resource and demands outreach to both patients and potential donors.

Visceral Adiposity Independently Predicts Time to Flare in Inflammatory Bowel Disease but Body Mass Index Does Not.

BACKGROUND: Obesity is associated with progression of inflammatory bowel disease (IBD). Visceral adiposity may be a more meaningful measure of obesity compared with traditional measures such as body mass index (BMI). This study compared visceral adiposity vs BMI as predictors of time to IBD flare among patients with Crohn's disease and ulcerative colitis. METHODS: This was a retrospective cohort study. IBD patients were included if they had a colonoscopy and computed tomography (CT) scan within a 30-day window of an IBD flare. They were followed for 6 months or until their next flare. The primary exposure was the ratio of visceral adipose tissue to subcutaneous adipose tissue (VAT:SAT) obtained from CT imaging. BMI was calculated at the time of index CT scan. RESULTS: A total of 100 Crohn's disease and 100 ulcerative colitis patients were included. The median age was 43 (interquartile range, 31-58) years, 39% had disease duration of 10 years or more, and 14% had severe disease activity on endoscopic examination. Overall, 23% of the cohort flared with median time to flare 90 (interquartile range, 67-117) days. Higher VAT:SAT was associated with shorter time to IBD flare (hazard ratio of 4.8 for VAT:SAT ≥1.0 vs VAT:SAT ratio <1.0), whereas higher BMI was not associated with shorter time to flare (hazard ratio of 0.73 for BMI ≥25 kg/m2 vs BMI <25 kg/m2). The relationship between increased VAT:SAT and shorter time to flare appeared stronger for Crohn's than for ulcerative colitis. CONCLUSIONS: Visceral adiposity was associated with decreased time to IBD flare, but BMI was not. Future studies could test whether interventions that decrease visceral adiposity will improve IBD disease activity.

An increased ratio of visceral to subcutaneous adipose tissue was associated with a shorter time to flare in patients with both Crohn's and ulcerative colitis. Conversely, increased body mass index was not associated with a shorter time to flare in inflammatory bowel disease patients.

COVID-19 in patients with liver disease and liver transplant: clinical implications, prevention, and management.

The coronavirus disease 2019 (COVID-19) pandemic has had enormous implications for the care of patients with chronic liver disease (CLD), cirrhosis, and liver transplant (LT). Clinical outcomes of COVID-19 vary in patients with CLD and cirrhosis compared to healthy controls, and in patients with LT compared to patients without LT. Several special considerations apply to the approach to vaccination and treatment in patients with CLD and LT. The practice of liver transplantation has also been heavily impacted by the pandemic, including persistent reductions in living donor LT and increases in LT for an indication of alcohol-related liver disease. Recent medical society guidelines strive to standardize severe acute respiratory syndrome coronavirus 2 testing in donors and recipients and the approach to transplantation after recovered from COVID-19 infection, but certain controversies remain.

Visceral adiposity in cirrhosis: Association with disease severity and impact of liver transplantation.

BACKGROUND: Changes in adipose tissue distribution in liver cirrhosis are poorly characterized and may affect clinical outcomes. METHODS: Adult liver transplant (LT) January 2008-August 2017 recipients with abdominal MRI within 6 months pre-LT were retrospectively assessed. Visceral adipose tissue, subcutaneous adipose tissue, and skeletal muscle area (cm2) were determined at L3. Visceral-to-subcutaneous adipose tissue ratio (VSR) was used to define relative adipose distribution, stratified by sex. Correlation was tested with Pearson. Body composition measures were compared by Child-Turcotte-Pugh (CTP) class, before and after LT, and evaluated as predictors of clinical outcomes. RESULTS: A total of 318 patients were studied. Mean age was 56 years, 33.64% were female, and 47.80% had CTP C cirrhosis. CTP C was associated with a 0.42-point increase in VSR compared with CTP A (95% CI = 0.13-0.71, p < 0.01), adjusting for age, sex, diabetes, and HCC. Among the 79 (24.84%) patients with repeat MRI 1-2 years after LT, VSR significantly improved from before LT (1.31 vs. 0.95, p < 0.01). In adjusted analysis, CTP C was associated with a 0.86-point decrease in post-LT VSR compared with pre-LT VSR (95% CI = -1.27 to -0.44, p < 0.01). Body mass index poorly correlated with VSR before and after LT. Elevated pre-LT VSR trended toward an association with a 7.17-point decrease in pre-LT glomerular filtration rate (95% CI = -14.35 to -0.02, p = 0.05), adjusting for CTP C, age, sex, diabetes, hypertension, pre-LT sarcopenia, and hepatocellular carcinoma. Elevated pre-LT VSR did not affect 3-year post-LT mortality (log-rank p = 0.24). CONCLUSIONS: Poorly represented by body mass index, visceral adiposity is increased in cirrhosis and is associated with CTP class. However, this adipose redistribution may be modifiable by LT.

COVID-19 and Effect on Liver Transplant.

PURPOSE OF REVIEW: The Coronavirus disease-2019 (COVID-19) pandemic has significantly impacted all aspects of liver transplantation. We reviewed the literature regarding COVID-19 clinical outcomes, treatment, and vaccination of liver transplant candidates and recipients. RECENT FINDINGS: Patients with chronic liver disease, especially with cirrhosis, have higher morbidity and mortality from COVID-19 than patients without liver disease. Increased mortality has not been consistently seen in liver transplant recipients, in whom severe disease is more strongly associated advanced age and medical comorbidities, rather than with transplant-specific factors. While several targeted COVID-19 therapies have reported hepatotoxicity, these therapies may be safe and effective in patients with liver disease and liver transplant recipients. Questions remain regarding whether SARS-CoV-2 can be transmitted via the donor liver and whether transplant is safe in patients and/or donors with recent or active COVID-19. SUMMARY: COVID-19 has significantly affected the care of liver transplant candidates and recipients. Guidelines for the safe practice of liver transplantation are rapidly evolving, and current recommendations are discussed.

STAT signaling in the intestine.

The Janus kinase (JAK), signal transducer of activation (STAT) pathway, discovered by investigating interferon gene induction, is now recognized as an evolutionary conserved signaling pathway employed by diverse cytokines, interferons, growth factors, and related molecules. Since its discovery, this pathway has become a paradigm for membrane-to-nucleus signaling and explains how a broad range of soluble factors such as cytokines and hormones, mediate their diverse functions. The understanding of JAK-STAT signaling in the intestine has not only impacted basic science research, particularly in the understanding of intercellular communication and cell-extrinsic control of gene expression, but it has also become a prototype for transition of bench to bedside research, culminating in the clinical implementation of pathway-specific therapeutics.

Lack of Effect of Gluten Challenge on Fecal Microbiome in Patients With Celiac Disease and Non-Celiac Gluten Sensitivity.

INTRODUCTION: Celiac disease (CD) may be associated with gut microbial dysbiosis. Whether discrete gluten exposure in subjects with well-controlled disease on a gluten-free diet impacts the gut microbiome is unknown and may have implications for understanding disease activity and symptoms. We conducted a prospective study to evaluate the impact of gluten exposure on the gut microbiome in patients with CD and nonceliac gluten sensitivity (NCGS). METHODS: Subjects with CD (n = 9) and NCGS (n = 8) previously on a gluten-free diet were administered a 14-day gluten challenge (5 g of gluten per day) and compared with controls (n = 8) on a usual gluten-containing diet. Stool was collected for fecal microbiome analysis using 16S rRNA gene and metagenomic sequencing before, during, and after the gluten challenge. Symptoms were assessed using 2 validated clinical scales. RESULTS: Among subjects with CD and NCGS, there were no significant fecal microbial changes in response to gluten challenge. Gut microbiome composition differed among controls, subjects with CD, and subjects with NCGS at baseline, and these differences persisted despite gluten exposure. Gastrointestinal and general health symptoms reported by subjects with CD and NCGS were worst in the middle of gluten challenge and lessened by its end, with no consistent associations with gut microbiome composition. DISCUSSION: Pre-existing fecal microbiome diversity was unaffected by gluten challenge in adult subjects with CD and NCGS. These findings suggest that current microbiome status is unrelated to current disease activity and disease severity.

Oral Microbiome Alterations and SARS-CoV-2 Saliva Viral Load in Patients with COVID-19.

Bacterial-viral interactions in saliva have been associated with morbidity and mortality for respiratory viruses such as influenza and SARS-CoV. However, such transkingdom relationships during SARS-CoV-2 infection are currently unknown. Here, we aimed to elucidate the relationship between saliva microbiota and SARS-CoV-2 in a cohort of newly hospitalized COVID-19 patients and controls. We used 16S rRNA sequencing to compare microbiome diversity and taxonomic composition between COVID-19 patients (n = 53) and controls (n = 59) and based on saliva SARS-CoV-2 viral load as measured using reverse transcription PCR (RT-PCR). The saliva microbiome did not differ markedly between COVID-19 patients and controls. However, we identified significant differential abundance of numerous taxa based on saliva SARS-CoV-2 viral load, including multiple species within Streptococcus and Prevotella. IMPORTANCE Alterations to the saliva microbiome based on SARS-CoV-2 viral load indicate potential biologically relevant bacterial-viral relationships which may affect clinical outcomes in COVID-19 disease.

Combined Endoscopic Stricturotomy and Balloon Dilation of Strictureplasty Site Stricture in Jejunal Crohn's Disease.

Patients who undergo surgical strictureplasty for jejunal Crohn's disease-associated strictures may develop severe stenosis at the inlet and outlet sites of the strictureplasty. There is currently no consensus on the optimal management of these strictureplasty-associated strictures because immunosuppressive medications will be ineffective and surgical reintervention, most commonly with bowel resection, is invasive and may introduce new complications. Endoscopic therapy may sometimes be the only valid option. We present a case of severe strictureplasty inlet and outlet strictures that were successfully treated with combined endoscopic stricturotomy and balloon dilation.

Alterations to the Esophageal Microbiome Associated with Progression from Barrett's Esophagus to Esophageal Adenocarcinoma.

BACKGROUND: The incidence of esophageal adenocarcinoma has risen dramatically over the past half century, and the underlying reasons are incompletely understood. Broad shifts to the upper gastrointestinal microbiome may be partly responsible. The goal of this study was to describe alterations in the esophageal microbiome that occur with progression from Barrett's esophagus to esophageal adenocarcinoma. METHODS: A case-control study was performed of patients with and without Barrett's esophagus who were scheduled to undergo upper endoscopy. Demographic, clinical, and dietary intake data were collected, and esophageal brushings were collected during the endoscopy. 16S rRNA gene sequencing was performed to characterize the microbiome. RESULTS: A total of 45 patients were enrolled and included in the analyses [16 controls; 14 Barrett's esophagus without dysplasia (NDBE); 6 low-grade dysplasia (LGD); 5 high-grade dysplasia (HGD); and 4 esophageal adenocarcinoma]. There was no difference in alpha diversity between non-Barrett's esophagus and Barrett's esophagus, but there was evidence of decreased diversity in patients with esophageal adenocarcinoma as assessed by Simpson index. There was an apparent shift in composition at the transition from LGD to HGD, and patients with HGD and esophageal adenocarcinoma had decreased Firmicutes and increased Proteobacteria. In addition, patients with HGD or esophageal adenocarcinoma had increased Enterobacteriaceae and Akkermansia muciniphila and reduced Veillonella. In the study population, patients taking proton pump inhibitors had increased Streptococcus and decreased Gram-negative bacteria overall. CONCLUSIONS: Shifts in the Barrett's esophagus-associated microbiome were observed in patients with HGD and esophageal adenocarcinoma, with increases in certain potentially pathogenic bacteria. IMPACT: The microbiome may play a role in esophageal carcinogenesis.