Development and validation of a prediction model for histologic progression in patients with nondysplastic Barrett's esophagus.

OBJECTIVES: Patients with Barrett's esophagus (BE) are at risk of progression to esophageal adenocarcinoma (EAC). We developed a model to predict histologic progression in patients with nondysplastic BE (NDBE). METHODS: A longitudinal study in three referral centers was performed between January 2010 and December 2019. As progression to low-grade dysplasia (LGD) can be considered an indication for ablative therapy, the study end-point was histopathologic progression to LGD, high-grade dysplasia, or EAC at 3 years after diagnosis. We used logistic regression to create the model. Seventy percent of the cohort were used to stem the model and the remaining 30% for internal validation. RESULTS: A total of 542 patients were included, 69.4% of whom were male, mean age 62.2 years. Long-segment BE at index endoscopy was diagnosed in 20.8% of the patients. After a mean follow-up of 6.7 years, 133 patients (24.5%) had histologic progression. Our model identified a neutrophil-to-lymphocyte ratio (odds ratio [OR] 2.08, 95% confidence interval [CI] 1.77-2.32, P < 0.001), BE length (OR 1.22, 95% CI 1.09-1.36, P < 0.001), age (OR 1.03, 95% CI 1.02-1.05, P = 0.02), smoking (OR 1.66, 95% CI 1.09-2.75, P = 0.04), and renal failure (OR 1.51, 95% CI 0.93-2.43, P = 0.07) as predictors of histologic progression at 3 years. The areas under the receiver operating characteristic curves of this model were 0.88 and 0.76 in the training and validation cohorts, respectively. CONCLUSION: This novel, internally validated model may predict histologic progression, even in patients with NDBE who generally have low rates of progression over time, and may contribute to enhanced patient selection for more intense surveillance programs.

Neutrophil to lymphocyte ratio and risk of neoplastic progression in patients with Barrett's esophagus.

BACKGROUND: Patient's with Barrett's esophagus (BE) are at risk of progression to esophageal adenocarcinoma (EAC). Neutrophil to lymphocyte ratio (NLR) was found to be a predictor of poor prognosis in patients with EAC; however, its performance in premalignant esophageal lesions is vague. We aimed to evaluate the utility of NLR as a predictor of histologic progression in patients with BE. METHODS : A prospective cohort of patients with proven BE in a tertiary referral center was retrospectively analyzed. All biopsies were reviewed by an expert gastrointestinal pathologist. The discriminatory capacity of NLR was evaluated by area under the receiver operating characteristic (AUC) curve analysis and Cox regression analysis. RESULTS: 324 patients (mean age 62.3 years, 241 [74.4 %] males) were included in the final analysis. Overall, 13 patients demonstrated histologic progression to neoplasia over a mean follow-up of 3.7 years (progression risk 1.0 % per year). The AUC of NLR for progression to high grade dysplasia (HGD) or EAC was 0.88 (95 % confidence interval [CI] 0.83 - 0.96), and baseline NLR was associated with a 3-fold increase of progression to HGD and EAC during follow-up (hazard ratio [HR] 3.2, 95 %CI 1.5 - 5.8; P < 0.001). Notably, in a subgroup analysis of patients with nondysplastic BE (NDBE) at presentation, NLR was also a risk factor for histologic progression (HR 2.4, 95 %CI 1.7 - 3.4; P < 0.001). CONCLUSION: NLR predicted histologic progression in patients with BE. Patients with NDBE and NLR above 2.4 can be considered for specific surveillance programs with shorter intervals between sessions.

[THE INFLUENCE OF GLUTEN ON THE SHARPNESS OF VISION].

INTRODUCTION: An eighty five old male was diagnosed with celiac disease. Six months before the diagnosis he complained of difficulties in his sight. In an optimetrical examination a decline in sharpness of sight was found: Right (R) - 6/19, Left (L) - 6/12. Following a few months of a gluten-free diet his situation improved and the signs of celiac disease disappeared. The sharpness of sight was re-examined and good improvement was found: L - 6/9, R - 6/12. This means that gluten might influence the sharpness of sight.

Increasing Serum Albumin Level Shortly After Gastrostomy Tube Insertion Predicts Longer Survival in Elderly Patients With Dementia.

GOAL: To identify factors influencing survival after percutaneous endoscopic gastrostomy (PEG) tube insertion in elderly patients with severe dementia. BACKGROUND: Use of PEG in patients with dementia raises medical and ethical questions. STUDY: The cohort included 189 patients aged ≥64 years with severe dementia who underwent PEG tube insertion in 2002 to 2011 at a tertiary hospital and were followed through 2014. Data were collected on background diseases, laboratory tests conducted 14 (±10) days before and 90 (±10) days after PEG, and date of death. Multivariate Cox regression analysis was performed and cumulative survival curves plotted. RESULTS: Mean baseline serum albumin level was significantly lower in patients who died ≤30 days after PEG (n=32, 16.9%) than patients who survived longer (2.9±0.5 vs. 3.3±0.5 g/dL, P<0.001), and significantly higher in patients who survived 1 year after PEG (n=96, 50.8%) than patients who died earlier (3.4±0.5 vs. 3.1±0.5 g/dL, P=0.002). No significant differences were found for the other laboratory parameters. After adjustment for background diseases, serum albumin level above the median (3.3 g/dL) was the only predictor of survival (hazard ratio 0.51; 95% confidence interval, 0.37-0.72; P<0.001). Patients with stable/increased serum albumin levels at 90 days after PEG (n=80, 42.3%) survived longer than patients with decreased levels. The only predictor of survival after adjustment for age and background diseases was a stable/increased albumin level at 90 days (hazard ratio 0.59; 95% confidence interval, 0.42-0.85; P=0.004). CONCLUSIONS: Survival after PEG tube insertion is associated with a higher serum albumin level at baseline and a stable/increased serum albumin level during follow-up.

Circulating Bone Marrow-Derived CD45-/CD34+/CD133+/VEGF+ Endothelial Progenitor Cells in Adults with Crohn's Disease.

BACKGROUND: Circulating endothelial progenitor cells (EPCs) are bone marrow-derived stem cells able to migrate to sites of damaged endothelium and differentiate into endothelial cells. Altered EPC level and function have been described in various inflammatory diseases and have been shown to augment vasculogenesis in murine models. Previous studies of EPC in the context of Crohn's disease (CD) have yielded conflicting results. AIM: To determine whether the circulating levels of EPCs are changed in the context of CD. METHODS: CD patients and healthy controls were recruited. Disease activity was assessed by CDAI. Peripheral blood mononuclear cells were isolated and EPC numbers evaluated by FACS analysis using anti-CD34, anti-VEGF receptor-2, anti-CD133, and anti-CD45 markers. RESULTS: Eighty-three subjects, including 32 CD patients and 51 controls were recruited, including 19 (59.4 %) and 23 (45 %) males (p = 0.26), aged 34.8 ± 14.9 and 43.3 ± 18.5 years (p = 0.64), in cases and controls, respectively. Mean CDAI was 147 ± 97, disease duration was 12.7 ± 11.1 years, and 28 (87.5 %) were receiving biologics for a mean duration of 21.7 ± 16.8 months. The mean level of peripheral EPCs in CD patients was 0.050 ± 0.086 percent and 0.007 ± 0.013 % in controls (p < 0.01). There was no significant correlation between EPC levels and age (r = -0.13, p = 0.47), CDAI (r = -0.26, p = 0.15), disease duration (r = -0.04, p = 0.84), or duration of treatment with biologics (r = 0.004, p = 0.99). CONCLUSION: EPCs are elevated in patients with CD. Further studies are needed to examine the function of EPCs and their possible role as a marker of disease severity or therapeutic response.

Seattle Protocol Is More Effective in Detection of Dysplasia Compared to Technology-Assisted Targeted Biopsies in Patients with Barrett's Esophagus.

BACKGROUND AND AIMS: With the development of narrow-band imaging (NBI) in the endoscopic evaluation of patients with Barrett's esophagus (BE), the role of random biopsies according to the Seattle protocol (SP) has been questioned. We aim to compare the utility of advanced imaging to SP in patients with BE. METHODS: A prospective cohort of patients with proven BE was retrospectively analyzed. All biopsies were reviewed by an expert GI pathologist. Advanced imaging was tandemly used with SP in each endoscopic procedure. RESULTS: A total of 155 out of 340 patients (45.5%) with BE were diagnosed with dysplasia during a median follow-up of 4.7 years (IQR 3.4-6.1 years) and were part of the statistical analysis. A total of 82 patients had a diagnosis of dysplasia at presentation, whereas 84 patients developed dysplasia during follow up. A total of 67 out of 82 patients with dysplasia at presentation (81.7%), and 65 out of 84 patients that were diagnosed with dysplasia during follow-up (77.4%) were diagnosed using SP. In addition, whereas all the events of EAC were diagnosed using targeted biopsies, 57.1% of the events of HGD and 86.3% of LGD were diagnosed using SP. CONCLUSION: Our findings demonstrate the significance of SP in the detection of low- and high-grade dysplasia in patients with BE. SP should remain the mainstay of endoscopic surveillance in this population.

Multi-focal dysplasia is associated with high recurrence rates after successful ablation of dysplastic Barrett's esophagus.

BACKGROUND & AIMS: Barrett's esophagus (BE) might recur after complete eradication of intestinal metaplasia (CEIM). We investigated  factors associated with recurrence of BE after successful Radiofrequency ablation (RFA). METHODS: A longitudinal study of BE patients with dysplasia treated with RFA from 2014 to 2021 in two large referral centers. Recurrence was identified in histologic specimens. Factors associated with post-RFA recurrence were analyzed using Cox regression analysis. RESULTS: A total of 728 patients with BE were identified, 118 had underwent RFA, and 113 had sufficient follow up time. Mean age was 63.7 (±11.7) years, 73.5% were males, 59.3% had long segment of BE, and 30.1% had multifocal dysplasia. During 340.8 patient-years of follow-up, 15 patients (13.3%) had recurrence of BE, which represent an incidence rate of 4.41% per patient-year. Incidence rate of recurrence with dysplasia was 1.17% per patient-year. Multifocal dysplasia, number of RFA sessions, and endoscopic resection before RFA were associated with risk of recurrence in univariate analysis. However, in cox regression analysis only multifocal dysplasia (HR 10.99; 95% CI 2.83-22.62, p = 0.001) was associated with post-RFA recurrence. CONCLUSION: Total recurrence rates after CEIM are low, and multifocal dysplasia before the ablative therapy is significantly associated with BE recurrence after CEIM. Patients with multifocal dysplasia should be monitored rigorously after successful ablation.

Predictors of poor outcome following liver biopsy for the investigation of new hepatic space occupying lesion/s.

BACKGROUND: Ultrasound-guided percutaneous liver biopsy (UPLB) is currently performed mainly to determine if new hepatic space occupying lesions (SOL) represent benign, primary malignant, or metastatic disease. This study sought to investigate the outcome of UPLB in this setting. METHODS: In a retrospective study, patients with a new hepatic SOL who underwent UPLB during 1/2006-12/2016 were included and followed to 12/2018. Clinical data and pathology reports were reviewed. Mortality within 60 days and no change in patients' management following UPLB were defined as medically futile. RESULTS: Included 140 patients, 50% male, mean age 68.8 ± 11.5 years; 112 patients died, all of malignant disease. 32 patients (23%) died within 60 days of UPLB. Median post-UPLB survival was 151 days. Survival was significantly shorter in patients with >1 hepatic lesion (n = 108) or an extrahepatic malignant lesion (n = 77) (p = 0.0082, p = 0.0301, respectively). On Cox Proportional Hazards analysis, significant predictors of mortality within 60 days of UPLB were: age as a continuous variable, (HR 1.070, 95% CI 1.011-1.131, p = 0.018), serum albumin <2.9 g/dL, (HR 4.822 95% CI 1.335-17.425, p = 0.016) and serum LDH >1500 U/L (HR 9.443, 95% CI 3.404-26.197, p < 0.0001). CONCLUSIONS: In patients with these features or with disseminated disease, liver biopsy should be carefully reconsidered.

[¹¹C] choline as a potential PET/CT biomarker of liver cirrhosis: A prospective pilot study.

AIM OF THE STUDY: To compare [¹¹C] choline PET/CT findings between patients with cirrhosis and normal liver controls. METHODS: Included 11 patients with cirrhosis and 14 controls. All underwent a dynamic [11C] choline PET/CT. The maximal standard uptake values (SUVmax), the area under the curve (AUC) and kinetic parameters (K1 and K2), clinical and laboratory data, were compared between groups. RESULTS: Patients mean age was 68.4 ±â€¯10.7 and controls, 69.7 ±â€¯7.3 years. Mean SUVmax was higher in patients than controls (right lobe, 10.06 ±â€¯12 vs. 6.3 ±â€¯1.6, P = 0.011; left lobe, 8.6 ±â€¯11.6 vs. 5.4 ±â€¯0.9, P = 0.024; spleen 17.99 ±â€¯27.8 vs. 13.4 ±â€¯2.6, P = 0.027; kidney, 35.9 ±â€¯59.5 vs. 19.3 ±â€¯4.8, P = 0.025) and also AUC values (right lobe, 13,538 ±â€¯20,020 vs. 8427.3 ±â€¯1557.9, P = 0.026; left lobe 12,304 ±â€¯18,871 vs. 6878.9 ±â€¯1294.3, P = 0.024; spleen, 12,875 ±â€¯17,930 vs. 8263.9 ±â€¯1279.2, P = 0.023; kidney, 24,623 ±â€¯36,025 vs. 13,667 ±â€¯3873.9, P = 0.032). No difference in kinetic parameters was found. No correlations between severity of clinical signs and imaging-derived parametric data were found among patients with cirrhosis. CONCLUSIONS: [11C] choline PET/CT may serve as a noninvasive biomarker for patients with cirrhosis.

Primary and secondary nonvariceal upper gastrointestinal bleeding.

BACKGROUND: Upper gastrointestinal (UGI) bleeding is associated with a mortality rate of up to 14% in emergency hospital admissions (primary bleeding), and up to 28% in hospitalized patients (secondary bleeding). AIM: To characterize and compare the clinical pictures and outcome of primary and secondary nonvariceal UGI bleeding. STUDY: A retrospective, case-control design was used. The files of all consecutive patients admitted to our tertiary academic center between January 1, 2001 and December 31, 2002 for UGI bleeding were reviewed for demographic and clinical data, treatment details, number of blood transfusions, endoscopic procedures, surgical procedures, and mortality. RESULTS: Compared to primary UGI bleeding, secondary bleeding was associated with female sex, older age, more chronic diseases, intake of more drugs, hospitalization in internal medicine departments, longer hospital stay, fewer endoscopic procedures, and less Helicobacter pylori-related peptic ulcer disease. Total mortality rate in the secondary bleeders was 30.3% versus 4.6% in the primary bleeders (P<0.0001). There was no significant difference between primary and secondary bleeders in treatment with nonsteroidal anti-inflammatory agents or aspirin, severity of bleeding, or death related to gastrointestinal bleeding. CONCLUSIONS: Despite the significant differences in the clinical picture of primary and secondary bleeders, the severity of bleeding appear to be similar in both groups. Although there was a trend towards a higher gastrointestinal-related mortality in secondary bleeders, it was not statistically significant.

Follicular lymphoma with extensive gastrointestinal tract involvement: follow-up by capsule endoscopy.

Follicular lymphoma with gastrointestinal tract involvement is rare. We describe the case of a young woman with follicular lymphoma with multiple nodular lesions involving segments of the proximal jejunum and terminal ileum. The presenting symptom was chronic diarrhea. The diagnosis was made by endoscopy with histologic examination of the mucosal lesions of the proximal and distal small intestine, immunohistochemical staining, and molecular analysis. The initial spread and pattern of the small bowel involvement, as well as treatment response, were evaluated by videocapsule endoscopy. The application of molecular analysis along with immunophenotypic evaluation has made it possible to precisely diagnose follicular lymphoma. In the present case, the use of capsule endoscopy improved the evaluation of the extent of small bowel involvement prior to and following treatment.

Assessment of orthostatic hypotension in the emergency room.

The study sought to determine the duration of standing needed to detect most cases of orthostatic hypotension (OH) in the emergency room (ER) and to correlate OH with symptoms, hospitalization and survival. Patients attending a tertiary-center ER within a 2-month period underwent orthostatic tests after 1, 3 and 5 min of standing. OH was defined as a drop of > or = 20 mmHg in systolic pressure or > or = 10 mmHg in diastolic pressure on assuming an upright posture. Of the 814 patients tested (402 men, mean age 56.6 +/- 19.9 years), 206 (25.3%) had OH, detected in most cases (83.5%) after 3 min of standing. OH was associated with significantly higher supine systolic (p = 0.013) and diastolic (p = 0.004) blood pressure, symptoms of syncope (r = 0.11, p < 0.001) or dizziness (r = 0.14, p < 0.0001) and risk of hospitalization (50.9% vs 22.9%, p < 0.0001). Crude mortality was similar between patients with and without OH (13.8% vs 8.7%, p = 0.06). However, on age-adjusted analysis, patients older than 75 years with OH had significantly increased mortality (p = 0.04). In conclusion, 3 min of standing is apparently sufficient for the diagnosis of most cases of OH. Considering the high rate of OH and its predictive value for hospitalization, it should be routinely assessed in all ER patients.

Endoscopy in asymptomatic minidose aspirin consumers.

Aspirin is widely used for its antiplatelet activity, but it harbors a risk of severe adverse gastrointestinal effects, such as bleeding and perforation, especially in elderly people. Our aim to assess the prevalence of upper gastrointestinal lesions and the effect of aspirin on the gastrointestinal mucosa in asymptomatic subjects taking minidose aspirin (100 to 325 mg per day) for more than 3 months. A prospective, open design was used. Patients attending the ophthalmology and cardiology outpatient clinics who had a medical history of more than 3 months of regular aspirin consumption were referred for esophagogastroduodenoscopy (EGD). Of the 90 patients referred for EGD, 44 were symptomatic (epigastric pain or dyspepsia) and were excluded from the study. The 46 asymptomatic patients included 22 men and 24 women of mean age 70 +/- 10 years (range, 36 to 87 years); 32% were current or former smokers. Mean daily aspirin dose was 129.34 +/- 76.61 mg. Only 24% were taking a gastroprotective agent. EGD revealed ulcer or erosions in 47.83% of the patients: erosive gastroduodenitis in 13 patients, gastric ulcer in 14, duodenal ulcer in 2, and gastric and duodenal ulcers in 2. Urease test for Helicobacter pylori infection was positive in 26%. Univariate and multivariate analysis revealed no factor other than aspirin predictive of a positive endoscopy. Minidose aspirin treatment is associated with a high prevalence of ulcerations of the stomach and duodenum.

Minidose aspirin and gastrointestinal bleeding--a retrospective, case-control study in hospitalized patients.

Low or minimal doses of aspirin are widely used for prevention of cardiovascular diseases. Aspirin is known to produce severe adverse gastrointestinal effects, such as bleeding and perforation. Less is known about the risk associated with minidose aspirin. Our aim was to assess the possible association of upper gastrointestinal tract bleeding with minidose aspirin therapy. A retrospective controlled design was used. Patients hospitalized for melena or hematemesis between January 1, 2000, and December 31, 2001, were identified by ICD-9 codes, and their clinical findings were compared to these of patients without upper gastrointestinal bleeding hospitalized during the same period and matched for age and sex. Bleeding was attributed to therapy if patients used a nonsteroidal anti-inflammatory drug or aspirin therapy within 30 days before hospitalization. The study group included 318 patients (59% male), and the control group 141 (65% male). Mean ages were 67 +/- 19 and 64 +/- 19 years, respectively. Study patients had more accompanying diseases, used more medications, and required more blood transfusions than controls (37%, vs. 2% of controls; P < 0.001). Minidose aspirin was used by 28% of the study group and 18% of the controls (P = 0.03). The average dose was 40 +/- 86 and 21 +/- 55 mg/day, respectively (P = 0.012). Only 26% of the study patients received a gastric protective agent. On multivariate analysis, aspirin consumption was the only independent risk factor for upper gastrointestinal tract bleeding. There appears to be an association between minidose aspirin treatment and hospitalization for upper gastrointestinal tract bleeding. Despite the advanced age of the patients, only one-quarter were treated with gastric protective agent.