Icteric Variant of Stauffer Syndrome as a Paraneoplastic Manifestation of Type 1 Papillary Renal Cell Carcinoma.

Intrahepatic cholestasis as a paraneoplastic manifestation was first described by Dr. Maurice H. Stauffer in 1961. This paraneoplastic manifestation was primarily associated with renal cell carcinoma characterized by abnormal liver enzymes without hepatic metastasis. Stauffer syndrome is classified into 2 types: classical and jaundice variants. Indeed, the jaundice variant is extremely rare and only described in 13 published cases. We report a case of intrahepatic cholestasis associated with a type 1 papillary renal cell carcinoma with complete resolution after surgical treatment.

Association between genetic polymorphisms of NOD1, Interleukin-1B, and cagA strain with low-grade duodenal eosinophilia in Helicobacter pylori-related dyspepsia.

BACKGROUND: Functional dyspepsia (FD) is a multifactorial disorder. Helicobacter pylori (H. pylori)-related dyspepsia (HpD) may be considered a separate entity. Duodenal eosinophilia is a potential pathogenic mechanism in FD. However, the impact of duodenal eosinophilia and host genetic polymorphism of innate and pro-inflammatory cascade, nucleotide-binding oligomerization domain 1 (NOD-1), and interleukin-1 beta (IL-1ß) in HpD was not explored. AIM: To evaluate the association of NOD1-796G>A and IL-1B-511C>T gene variants and low-grade duodenal eosinophilia in HpD. METHODS: A multicenter cross-sectional study was conducted. A total of 253 patients who met Rome-IV criteria were selected before upper endoscopy and 98 patients were included after unremarkable upper endoscopy and positive H. pylori in gastric biopsies were assessed. Clinical parameters, H. pylori cagA and duodenal histology, were evaluated. RESULTS: Sixty-four (65%) patients had epigastric pain syndrome (EPS), 24 (25%) postprandial distress syndrome (PDS), and 10 (10%) EPS/PDS overlap. FD subtypes were not associated with NOD1-796G>A and IL-1B-511C>T gene variants. Low-grade duodenal eosinophilia was significantly increased in NOD1-796 GG versus single A-allele, but not in IL-1B-511 single T-allele or CC-allele. This association is dependent of cagA infection, since harboring cagA strain was significantly associated with low-grade duodenal eosinophilia with isolated variants NOD1-796 GG and IL-1B-511 single T-allele, but not without cagA. When we performed combined polymorphism analysis with NOD1-796 GG/IL-1B-511 single T-allele, a synergistic effect on low-grade duodenal eosinophilia was found between these two loci irrespective of cagA strain status in HpD. CONCLUSION: Our findings suggest that low-grade duodenal eosinophilia is significantly associated with NOD1-796 GG allele specially in cagA strain and with allelic combination NOD1-796 GG/IL-1B-511 single T-allele independent of cagA strain infection in HpD patients.

Clinical Implications of Low-grade Duodenal Eosinophilia in Functional Dyspepsia: A Prospective Real-life Study.

BACKGROUND: Functional dyspepsia (FD) is a multifactorial disorder with no targeted therapy. Duodenal eosinophilia and low-grade inflammation are potential pathogenic mechanisms. However, the impact of duodenal eosinophils (D-EO) histologic evaluation in real-life clinical practice was not explored. AIM: To evaluate the clinical utility of D-EO and low-grade inflammation in FD in real-life practice. MATERIALS AND METHODS: A multicenter prospective study was conducted. A total of 636 patients who meet Rome-III criteria were selected before upper endoscopy and 516 patients were included after normal endoscopy were assessed. Clinical parameters, Helicobacter pylori ( H. pylori), and duodenal histology were evaluated. RESULTS: FD subtypes were 231 (45%) patients who had epigastric pain syndrome (EPS), 168 (33%) postprandial distress syndrome (PDS), and 117 (22%) EPS/PDS overlap. Two hundred fifty-nine (50.3%) patients were H. pylori+ . Histologic duodenal grading of chronic inflammation and intraepithelial lymphocytes showed no difference between FD subtypes. Increased in D-EO densities (>10 per high power field) was significant in PDS compared with EPS and EPS/PDS overlap subtypes. The odds ratio of PDS in subjects with duodenal eosinophilia densities was 2.28 (95% CI, 1.66-3.14; P <0.0001), adjusting for age, gender, H. pylori and nonsteroidal anti-inflammatory drug the odds ratio was 3.6 (95% CI, 2.45-5.28; P <0.0001). receiver operating characteristic curve analysis further demonstrated that low-grade duodenal eosinophilia, in particular H. pylori- , was highly accurate for PDS with the area under the curve 0.731 compared with H. pylori+ area under the curve 0.598. Furthermore, low-grade duodenal eosinophilia was significantly correlated with treatment response under 4 to 6 weeks of proton pump inhibitor therapy. CONCLUSION: Our findings suggest that low-grade duodenal eosinophilia is associated with PDS subtype non- H. pylori FD patients and could be a useful marker of treatment response.

Low-grade duodenal eosinophilia is associated with cagA in Helicobacter pylori-related dyspepsia.

BACKGROUND AND AIM: Functional dyspepsia (FD) is a multifactorial disorder. Helicobacter pylori (H. pylori)-related dyspepsia (HpD) may be considered a separate entity. Duodenal eosinophilia is a potential pathogenic mechanism in FD. However, the impact of duodenal eosinophilia and H. pylori virulence genes in HpD was not explored. We aim to evaluate the association of H. pylori virulence genes and low-grade duodenal eosinophilia in HpD. METHODS: A multi-center cross-sectional study was conducted. A total of 301 patients who meet Rome-III criteria were selected before upper endoscopy, and 95 patients were included after normal endoscopy and positive H. pylori in gastric biopsies were assessed. Clinical parameters, H. pylori virulence genes (cagA, oipA, and vacA) and duodenal histology were evaluated. RESULTS: Sixty-nine (72%) patients had epigastric pain syndrome (EPS), 17 (18%) post-prandial distress syndrome (PDS) and 9 (10%) EPS/PDS overlap. FD syndromes were not associated with cagA or oipA strains. A significantly trend of vacA s1/m1 (78%) and s1/m2 (80%) positive strains in EPS was observed. Histological duodenal grading of chronic inflammation, low-grade duodenal eosinophilia and intra-epithelial lymphocytes showed no difference in oipA and vacA strains. Low-grade duodenal eosinophilia was significant in cagA positive strain, and the OR for low-grade duodenal eosinophilia with H. pylori cagA positive strain was 4.2 (95% CI, 1.78-9.93). Adjusting for age, gender, smoking, diabetes, alcohol, PPI, and NSAID, the OR was 5.44 (1.989-14.902). CONCLUSION: Our findings suggest that low-grade duodenal eosinophilia is significantly associated with cagA strain in HpD.

Bezafibrate therapy in primary biliary cholangitis refractory to ursodeoxycholic acid: a longitudinal study of paired liver biopsies at 5 years of follow up.

BACKGROUND: Ursodeoxycholic acid (UDCA) is the first-line therapy for primary biliary cholangitis (PBC). However, nearly 40% of patients have an incomplete response to UDCA. The addition of bezafibrate has shown biochemical benefit in this group of patients. AIM: To evaluate the long-term effects of UDCA in combination with bezafibrate on histological outcomes in patients with UDCA-refractory PBC. METHODS: Fifty-nine patients refractory to UDCA were included. Clinical parameters were monitored and paired liver biopsy (PLB) was performed after 5 years of follow-up. RESULTS: Of the total cohort, 49 subjects were analysed and 31 had PLB at 5 years. Values for serum ALP, AST, ALT and GGT significantly improved with UDCA-bezafibrate. This beneficial effect was observed at 12 months where 86% achieved ALP at normal levels. Analyses of PLB showed a significant decrease in liver damage as reflected by Ludwig (baseline 2.29 ± 1.2, to 1.84 ± 1 at year 5, P = 0.0242) and Ishak (baseline 6.19 ± 2.2 to 4.77 ± 2.2 at year 5, P = 0.0008) scores. Overall, regression of fibrosis was attained in 48% of patients. Furthermore, we observed a significant reduction in the proportion with cirrhosis from 19% at baseline to 3% at 5 years (P < 0.001). These beneficial effects were associated with better predictive risk scores using the GLOBE and UK-PBC prognosis models. CONCLUSIONS: Adding bezafibrate to UDCA in patients with UDCA-refractory PBC showed a significant decrease in fibrosis and inflammatory histological scores at 5 years. These beneficial effects warrant further evaluation in long-term cohort studies and controlled trials.