Rituximab and improved nodular regenerative hyperplasia-associated non-cirrhotic liver disease in common variable immunodeficiency: a case report and literature study

Common variable immunodeficiency (CVID) associated liver disease is an underrecognized and poorly studied non-infectious complication that lacks an established treatment. We describe a CVID patient with severe multiorgan complications, including non-cirrhotic portal hypertension secondary to nodular regenerative hyperplasia leading to diuretic-refractory ascites. Remarkably, treatment with rituximab, administered for concomitant immune thrombocytopenia, resulted in the complete and sustained resolution of portal hypertension and ascites. Our case, complemented with a literature review, suggests a beneficial effect of rituximab that warrants further research

Tacrolimus Drug Exposure Level and Smoking Are Modifiable Risk Factors for Early De Novo Malignancy After Liver Transplantation for Alcohol-Related Liver Disease

De novo malignancy (DNM) is the primary cause of mortality after liver transplantation (LT) for alcohol-related liver disease (ALD). However, data on risk factors for DNM development after LT are limited, specifically in patients with ALD. Therefore, we retrospectively analyzed all patients transplanted for ALD at our center before October 2016. Patients with a post-LT follow-up of <12 months, DNM within 12 months after LT, patients not on tacrolimus in the 1st year post-LT, and unknown smoking habits were excluded. Tacrolimus drug exposure level (TDEL) was calculated by area under the curve of trough levels in the 1st year post-LT. 174 patients received tacrolimus of which 19 (10.9%) patients developed a DNM between 12 and 60 months post-LT. Multivariate cox regression analysis identified TDEL [HR: 1.710 (1.211–2.414); p = 0.002], age [1.158 (1.076–1.246); p < 0.001], number of pack years pre-LT [HR: 1.021 (1.004–1.038); p = 0.014] and active smoking at LT [HR: 3.056 (1.072–8.715); p = 0.037] as independent risk factors for DNM. Tacrolimus dose minimization in the 1st year after LT and smoking cessation before LT might lower DNM risk in patients transplanted for ALD

Secondary sclerosing cholangitis: an emerging complication in critically ill COVID-19 patients

peer reviewe

Pancreatic Insufficiency and an Absent Gallbladder: Connecting the Dots Gallbladder Agenesis and Pancreatic Hypoplasia Owing to a GATA-6 Mutation

status: publishe

EUS-guided intrahepatic biliary drainage: a large retrospective series and subgroup comparison between percutaneous drainage in hilar stenoses or postsurgical anatomy

Background and study aims  Endoscopic ultrasound-guided intrahepatic biliary drainage (EUS-IBD) struggles to find a place in management algorithms, especially compared to percutaneous drainage (PTBD). In the setting of hilar stenoses or postsurgical anatomy data are even more limited. Patients and methods  All consecutive EUS-IBDs performed in our tertiary referral center between 2012 - 2019 were retrospectively evaluated. Rendez-vous (RVs), antegrade stenting (AS) and hepatico-gastrostomies (HGs) were compared. The predefined subgroup of EUS-IBD patients with proximal stenosis/surgically-altered anatomy was matched 1:1 with PTBD performed for the same indications. Efficacy, safety and events during follow-up were compared. Results  One hundred four EUS-IBDs were included (malignancies = 87.7 %). These consisted of 16 RVs, 43 ASs and 45 HGs. Technical and clinical success rates were 89.4 % and 96.2 %, respectively. Any-degree, severe and fatal adverse events (AEs) occurred in 23.3 %, 2.9 %, and 0.9 % respectively. Benign indications were more common among RVs while proximal stenoses, surgically-altered anatomy, and disconnected left ductal system among HGs. Procedures were shorter with HGs performed with specifically designed stents (25 vs . 48 minutes, P  = 0.004) and there was also a trend toward less dysfunction with those stents (6.7 % vs . 30 %, P  = 0.09) compared with previous approaches. Among patients with proximal stenosis/surgically-altered anatomy, EUS-IBD vs. PTBD showed higher rates of clinical success (97.4 % vs. 79.5 %, P  = 0.01), reduced post-procedural pain (17.8 % vs. 44.4 %, p = 0.004), shorter median hospital stay (7.5 vs 11.5 days, P  = 0.01), lower rates of stent dysfunction (15.8 % vs. 42.9 %, P  = 0.01), and the mean number of reinterventions was lower (0.4 vs. 2.8, P  < 0.0001). Conclusions  EUS-IBD has high technical and clinical success with an acceptable safety profile. HGs show comparable outcomes, which are likely to further improve with dedicated tools. For proximal strictures and surgically-altered anatomy, EUS-IBD seems superior to PTBD.status: publishe

EUS-guided gastroenterostomy: Less is more! The wireless EUS-guided gastroenterostomy simplified technique.

status: Published onlin

Hypoxia driven gene expression is an independent prognostic factor in stage II and III colon cancer patients

Purpose - Hypoxia is considered a major microenvironmental factor influencing cancer behavior. Our aim was to develop a hypoxia-based gene score that could identify high and low risk within stage II and III colon cancer patients. Experimental design - Differential gene expression of CaCo-2 colon cancer cells cultured in chronic hypoxia versus normoxia was tested for correlation with prognostic variables in published microarray data sets. These data sets were further used to downsize and optimize a gene score, which was subsequently determined in paraffin embedded material of 126 patients with colon cancer treated in our center. Results - In the CaCo-2 cells, 923 genes with a 2-fold change and Limma corrected p≤0.0001 were found differentially expressed in hypoxia versus normoxia. We identified 21 genes with prognostic value and overlapping in three different training sets and (n=224). With a fourth published data set (n=177), the six gene Colon Cancer Hypoxia Score (CCHS) was developed. Patients with low CCHS showed a significant better disease free survival at three years (77.3%) compared to high CCHS patients (46.4%) (Log rank, p=0.006). This was independently confirmed in an external patient cohort of 90 stage II patients (86.9% vs 52.2%, p=0.001). Conclusions - Hypoxia driven gene expression is associated with high recurrence rates in stage II and III colon cancer. A 6-gene score was found to be of independent prognostic value in these patients. Our findings require further validation and incorporation in the current knowledgee on molecular classification of colon cancer.status: publishe