W Reindl

Patient position and hypoxemia during propofol sedation for colonoscopy: a randomized trial

AIM To evaluate the benefits of the left lateral position in avoiding hypoxemic events in patients undergoing colonoscopy. METHODS We conducted a randomized, prospective, controlled trial at two study sites in Germany. Patients undergoing colonoscopy under propofol sedation were randomized to either the supine or left lateral position. The primary outcome was oxygen desaturation (SaO2<90%). Secondary outcome measures were apneic events, hypotension, patient satisfaction, propofol dosage, cecal intubation time, and adenoma detection. RESULTS A total of 412 patients were randomized 1:1 to undergo colonoscopy in the supine or left lateral position. No severe adverse events were observed in either group. Intention-to-treat analysis revealed no significant difference in the frequency of desaturation in the left lateral arm compared with the supine arm (6.8% vs. 12.1%; P=0.064). Patients in the left lateral arm showed lower apnea rates (9.4% vs. 16.2%; P= .040), but had more episodes of hypotension (12.3% vs. 2.9%; P<0.001). The frequency of repositioning was higher in the left lateral group. No significant differences were observed in patient satisfaction and cooperation, propofol dosage, or adenoma detection rate. Patients who were repositioned to facilitate endoscope passage were excluded from per-protocol analysis. The incidence of hypoxemia was lower for the left lateral than for the supine group in per-protocol analysis (1.8% vs. 11.2%; P=0.003). CONCLUSION The positioning of patients in the left lateral position during propofol sedation for colonoscopy results in lower desaturation rates provided the position can be maintained throughout endoscopy. ClinicalTrials.gov NCT02001792.

PPARγ-activation increases intestinal M1 macrophages and mitigates formation of serrated adenomas in mutant KRAS mice

ABSTRACT To identify novel hubs for cancer immunotherapy, we generated C57BL/6J mice with concomitant deletion of the drugable transcription factor PPARγ and transgenic overexpression of the mutant KRASG12V oncogene in enterocytes. Animals developed epithelial hyperplasia, transmural inflammation and serrated adenomas in the small intestine with infiltration of CD3+ FOXP3+ T-cells and macrophages into the lamina propria of the non-malignant mucosa. Within serrated polyps, CD3+ CD8+ T-cells and phosphorylated ERK1/2 were reduced and the senescence marker P21 and macrophage counts up-regulated, indicative of an immunosuppressive tissue microenvironment. Treatment of mutant KRASG12V mice with the PPARγ-agonist rosiglitazone augmented M1 macrophage numbers, reduced IL4 expression and diminished polyp load in mice. Rosiglitazone also promoted M1 polarisation of human THP1-derived macrophages and decreased Il4 mRNA in isolated murine lymphocytes. Thus, inhibition of the oncogenic driver mutant RAS by PPARγ in epithelial and immune cell compartments may be a future target for the prevention or treatment of human malignancies associated with intestinal inflammation.

Clinical and Histopathologic Features of Colorectal Adenocarcinoma in Crohn’s Disease

Goals: The aim of this study was to assess the histopathologic characteristics of colorectal carcinomas (CRC) in patients with Crohn’s disease (CD). Background: A higher frequency of microsatellite instability (MSI) is seen in mucinous compared with nonmucinous CRC which suggests that its pathogenesis involves distinct molecular pathways. Several publications reported a higher percentage of mucinous adenocarcinoma in CD patients with CRC. So far, there has been no investigation of MSI in CD patients with mucinous CRC. Study: The medical records of patients who underwent surgery for CRC were reviewed and those with a history of CD identified. The data of histologic classification and MSI status of the tumor were investigated. Results: Fourteen patients with CD-associated CRC were identified (5 female, 9 male) resulting in 20 CRC in total. Histologic investigation revealed 7 adenocarcinomas without a mucinous or signet ring cell component. All other CRCs harbored a mucinous (n=11) and/or signet ring cell (n=6) component. All tumors assessed for MSI were found to be microsatellite stable. Conclusions: Our data indicate that CRCs with signet ring cell and mucinous components were much more common in patients with CD than in patients with sporadic CRC. This observation suggests that CRC in CD represent an own entity with distinct histopathologic and molecular features. This may implicate potential consequences for diagnosis and therapy of CRC in CD in the future as well as new factors to identify patients with an increased risk for developing CRC in CD.

Prevalence of inflammatory bowel disease in alcoholic, non-alcoholic and autoimmune pancreatitis: Inflammatory bowel disease in pancreatitis

OBJECTIVES Patients with inflammatory bowel disease (IBD) frequently reveal features of pancreatic inflammation. However, the prevalence of IBD in patients with alcoholic pancreatitis (AP) and nonalcoholic pancreatitis (NAP) has not yet been determined, and the prevalence of IBD in patients with autoimmune pancreatitis (AiP) from Germany is unknown. AIMS Thus, we aimed, first, to determine the prevalence of IBD in AP, NAP, and AiP from a tertiary center in Germany and, second, to characterize patients with AiP and IBD. METHODS We performed a retrospective cross-sectional study to determine the prevalence of IBD in patients with different forms of pancreatitis presenting to our clinic. RESULTS Compared to the general population and to a control group with viral hepatitis from our clinic, we observed the most significant increase of IBD in patients with AiP (n = 3/28; p < 0.0001 vs. general population, binomial proportion test; p = 0.0112 vs. hepatitis group, Fishers exact test), followed by a significant increase in subjects with NAP (n = 11/278; p < 0.0001 vs. general population, binomial proportion test; p = 0.0338 vs. hepatitis group, Fishers exact test). A review of previous studies on the prevalence of IBD among patients with AiP revealed a combined prevalence of 12 % (n = 43/355). Type 2 AiP is significantly more often associated with IBD than type 1 AiP (n = 28/48, 58 % vs. n = 7/129, 5 %; combined patient cohort, p < 10E - 12; Fishers exact test). CONCLUSIONS Immune-mediated mechanisms related to IBD may participate in the development of AiP, especially AiP type 2, and may also increase the risk for the development of other forms of pancreatic inflammation.

Intrinsic neural network dysfunction in quiescent Crohn’s Disease

Psychological factors and comorbidities play an important role in inflammatory bowel diseases. Such comorbidity could be associated with a specific neural phenotype. Brain regions associated with emotion regulation and self-referential processing, including areas assigned to the “default mode network” (DMN), could be promising candidates in this regard. We investigated the functional integrity of multiple intrinsic neural networks in remitted patients with Crohn’s disease (CD) and sought to establish relationships between neural network connectivity and psychiatric symptoms. Fifteen CD patients in remission and 14 controls were investigated. We employed resting-state functional magnetic resonance imaging (fMRI) at 3 Tesla followed by a spatial Independent Component Analysis for fMRI data. Abnormal connectivity in CD patients was observed in DMN subsystems only (p < 0.05, cluster-corrected). Increased connectivity was found in the anterior cingulate and left superior medial frontal gyrus (aDMN) and the middle cingulate cortex (pDMN). Middle cingulate activity showed a significant association with anxiety scores in patients (p = 0.029). This study provides first evidence of selectively disrupted intrinsic neural network connectivity in CD and suggests abnormalities of self-referential neural networks. An increased sensitivity to self-related affective and somatic states in CD patients could account for these findings and explain a higher risk for anxiety symptoms.