Impact of cardiac and noncardiac cirrhosis on coronary revascularization outcomes from the National Inpatient Sample, 2016 to 2018.

Data on coronary revascularization in patients with cirrhosis are scarce because it is often deferred in the setting of significant comorbidities and coagulopathies. It is unknown whether patients with cardiac cirrhosis have a worse prognosis. The National Inpatient Sample was surveyed to identify patients who underwent percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) for acute coronary syndrome (ACS) from 2016 to 2018. Those with and without liver cirrhosis were propensity score-matched and compared within the PCI and CABG cohorts. Primary outcome was in-hospital mortality. Patients with cirrhosis were further classified into cardiac and noncardiac cirrhosis and their in-hospital mortalities were compared. A total of 1,069,730 PCIs and 273,715 CABGs were performed for ACS, of which 0.6% and 0.7%, respectively, were performed in patients with cirrhosis. In both the PCI cohort (odds ratio = 1.56; 95% confidence interval, 1.10-2.25; P = 0.01) and the CABG cohort (odds ratio = 2.34; 95% confidence interval, 1.19-4.62; P = 0.01), cirrhosis was associated with higher in-hospital mortality. In-hospital mortality was greatest in cardiac cirrhosis (8.4% and 7.1%), followed by noncardiac cirrhosis (5.5% and 5.0%) and no cirrhosis (2.6% and 2.3%) in PCI and CABG cohorts, respectively. Higher in-hospital mortality and periprocedural morbidities should be considered when performing coronary revascularization in patients with cirrhosis.

Carcinoid Heart Disease-Induced Right-Sided Heart Failure as a Culprit for Significant Ascites.

The diagnosis of carcinoid heart disease as a cause of ascites can be hard to establish. We report a patient with well-differentiated neuroendocrine neoplasm of the liver who presented with high serum ascites albumin gradient and high protein ascites due to carcinoid heart disease (CHD). As ascites caused by CHD are rare, the etiology can easily be overlooked, especially in the setting of alcohol use disorder and portal hypertension. Through our case report, we emphasize the importance of physical examination and peritoneal fluid analysis in the diagnosis of CHD. As the management of CHD requires a multidisciplinary approach, early diagnosis is crucial so that relevant specialists can have the opportunity for early intervention in order to produce the best patient outcome.

Different Approaches to the Management of Cholecystoenteric Fistula.

A cholecystoenteric fistula is an anomalous communicating tract between the gallbladder and any segment of the gastrointestinal tract. It is a rare complication of gallstone disease and typically affects elderly patients with multiple medical comorbidities. These fistulae can present in a variety of ways, and the diagnosis is often made only after extensive workup. Despite notable advances in imaging techniques in the last half-century, a considerable number of cases are still discovered incidentally during open or laparoscopic surgery. We present a series of 3 cases, each with different etiologies and presentations, but all of whom were found to have a cholecystoenteric fistula. Each case was managed differently, highlighting the diversity of this intriguing condition.

Diurnal Fasting During Ramadan Leading to Superior Mesenteric Artery Syndrome.

Superior mesenteric artery (SMA) syndrome is a favorite of anatomists and clinicians because it results from extrinsic compression of the duodenum by the 2 vascular structures forming the aortomesenteric angle (the descending abdominal aorta and the SMA). Although it is an uncommon cause of upper gastrointestinal obstruction, SMA syndrome can cause significant morbidity. It is more common in younger people. Historically, it has been associated with weight loss and eating disorders, but there are several other risk factors that should be considered in the workup. Cases of SMA syndrome are typically managed conservatively, but surgical referral and intervention may be considered in situations that fail conservative management. We present a case of this rare syndrome in a young man with no medical or psychiatric history during diurnal voluntary fasting in the month of Ramadan.

Schistosoma japonicum Associated With Colorectal Cancer.

Colorectal cancer (CRC) is one of the most common cancers worldwide, with increasing prevalence in Asian countries with a crude incidence of 21.1 per 100,000. Schistosoma is a genus of trematodes that infect millions of humans, affecting multiple organs, notably the intestines, liver, and bladder. Those trematodes may cause chronic inflammation in the affected organ leading to long-term complications such as fibrosis and neoplasia. There is rising evidence that infection with Schistosoma japonicum is correlated with the liver and CRC in endemic Asian countries. It is reported that chronic infection with Schistosomiasis raises the risk of CRC by 3 times. Less commonly seen outside of endemic areas, we present a case of S. japonicum-associated CRC in the United States in a woman with sigmoid adenocarcinoma and Schistosoma japonicum infection.

Acute Esophageal Necrosis: A Case Series From a Safety Net Hospital.

Acute esophageal necrosis (AEN) or "black esophagus" is a rare clinical condition, endoscopically characterized by diffuse circumferential black esophageal mucosa. Etiologies include hypoperfusion, infections, and corrosive injury. Consideration of this condition as a differential diagnosis is important, as early diagnosis and treatment has implications on survival. In this article, we present four unique cases of acute esophageal necrosis who were managed conservatively.

Fluoxetine-induced Stevens-Johnson syndrome and liver injury.

WHAT IS KNOWN AND OBJECTIVE: Drug-induced liver injuries (DILI) are overall rare and often associated with use of medications. Medications are also the most common aetiology of Stevens-Johnson syndrome (SJS), but SJS is seldom seen concomitantly with liver injury. Many common drugs can cause either one of these conditions; however, there are no reported cases of concomitant DILI and SJS secondary to fluoxetine. CASE SUMMARY: A 41-year-old female presented with a skin rash and abnormal liver function tests after the recent initiation of fluoxetine. Skin and liver biopsies showed features of SJS and DILI, respectively. Fluoxetine was stopped, following which there was improvement in her liver function tests and skin rash, without progression to fulminant hepatic failure. WHAT IS NEW AND CONCLUSION: Commonly used and safe pharmaceuticals such as fluoxetine have the potential for serious adverse events affecting the skin and liver.

Early increase in blood supply (EIBS) is associated with tumor risk in the Azoxymethane model of colon cancer.

BACKGROUND: The present study aimed to investigate the role of blood supply in early tumorigenesis in colorectal cancer. We leveraged the renin angiotensin system (RAS) to alter colonic blood supply and determine the effect on tumor initiation and progression. METHODS: To test the effect of blood supply on tumorigenesis, 53 male A/J mice were randomly assigned to one of three RAS modulation groups and one of two AOM treatments. The RAS modulation groups were I) water (RAS-unmodulated) as a control group, II) angiotensin-II and III) the angiotensin receptor blocker, Losartan. The mice in each group were then randomly split into either the saline control condition or the AOM-treated condition in which tumors were induced with a standard protocol of serial azoxymethane (AOM) injections. To monitor microvascular changes in the rectal mucosa during the study, we used confocal laser endomicroscopy (CLE) with FITC-Dextran for in-vivo imaging of vessels and polarization-gated spectroscopy (PGS) to quantify rectal hemoglobin concentration ([Hb]) and blood vessel radius (BVR). RESULTS: At 12 weeks post-AOM injections and before tumor formation, CLE images revealed many traditional hallmarks of angiogenesis including vessel dilation, loss of co-planarity, irregularity, and vessel sprouting in the pericryptal capillaries of the rectal mucosa in AOM-Water tumor bearing mice. PGS measurements at the same time-point showed increased rectal [Hb] and decreased BVR. At later time points, CLE images showed pronounced angiogenic features including irregular networks throughout the colon. Notably, the AOM-Losartan mice had significantly lower tumor multiplicity and did not exhibit the same angiogenic features observed with CLE, or the increase in [Hb] or decrease in BVR measured with PGS. The AOM-AngII mice did not have any significant trends. CONCLUSION: In-vivo PGS measurements of rectal colonic blood supply as well as CLE imaging revealed angiogenic disruptions to the capillary network prior to tumor formation. Losartan demonstrated an effective way to mitigate the changes to blood supply during tumorigenesis and reduce tumor multiplicity. These effects can be used in future studies to understand the early vessel changes observed.

miR-193a-3p is a Key Tumor Suppressor in Ulcerative Colitis-Associated Colon Cancer and Promotes Carcinogenesis through Upregulation of IL17RD.

Purpose: Patients with ulcerative colitis are at increased risk for colorectal cancer, although mechanisms underlying neoplastic transformation are poorly understood. We sought to evaluate the role of microRNAs in neoplasia development in this high-risk population.Experimental Design: Tissue from 12 controls, 9 ulcerative colitis patients without neoplasia, and 11 ulcerative colitis patients with neoplasia was analyzed. miRNA array analysis was performed and select miRNAs assayed by real-time PCR on the discovery cohort and a validation cohort. DNA methylation of miR-193a was assessed. Following transfection of miR-193a-3p, proliferation, IL17RD expression, and luciferase activity of the 3'UTR of IL17RD were measured. Tumor growth in xenografts as well as EGFR signaling were assessed in HCT116 cells expressing IL17RD with either a mutant 3' untranslated region (UTR) or wild-type (WT) 3'UTR.Results: miR-31, miR-34a, miR-106b, and miR-193a-3p were significantly dysregulated in ulcerative colitis-neoplasia and adjacent tissue. Significant down-regulation of miR-193a-3p was also seen in an independent cohort of ulcerative colitis cancers. Changes in methylation of miR-193a or expression of pri-miR-193a were not observed in ulcerative colitis cancer. Transfection of miR-193a-3p resulted in decreased proliferation, and identified IL17RD as a direct target of miR-193a-3p. IL17RD expression was increased in ulcerative colitis cancers, and miR-193a-3p treatment decreased growth and EGFR signaling of HCT116 cells in xenografts expressing both IL17RD with WT 3'UTR compared with cells expressing IL17RD with mutant 3'UTR.Conclusions: miR-193a-3p is downregulated in ulcerative colitis neoplasia, and its loss promotes carcinogenesis through upregulation of IL17RD. These findings provide novel insight into inflammation-driven colorectal cancer and could suggest new therapeutic targets in this high-risk population. Clin Cancer Res; 23(17); 5281-91. ©2017 AACR.

Serum 25-hydroxyvitamin D concentration is inversely associated with mucosal inflammation in patients with ulcerative colitis.

BACKGROUND: Vitamin D exerts anti-inflammatory actions both in vitro and in murine models of colitis. In previous studies, we demonstrated that vitamin D protects against the development of colitis by maintaining the integrity of the intestinal mucosal barrier. OBJECTIVE: We sought to evaluate whether deficient serum 25 hydroxyvitamin D [25(OH)D] concentrations are associated with increased mucosal inflammation, a loss of epithelial junctional proteins, and an increase in mucosal inflammatory cytokines in patients with ulcerative colitis (UC). DESIGN: We prospectively enrolled 230 subjects with UC. Serum 25(OH)D concentrations were compared with the Mayo endoscopic score, the total Mayo score, and histologic activity. Colonic mucosal expression concentrations of vitamin D receptor (VDR), E-cadherin, zonula occluden 1 (ZO-1), occludin, claudin-2, tumor necrosis factor α (TNF-α), and interleukin 8 (IL-8) were compared between dichotomous groups with low or high serum 25(OH)D concentrations. RESULTS: The mean serum 25(OH)D concentration was 21.8 ng/mL. Subjects stratified by concentrations included 12.6% ≥30 ng/mL, 45.6% ≥20 to <30 ng/mL, 37.4% ≥10 to <20 ng/mL, and 4.4% <10 ng/mL. There was an inverse association between serum 25(OH)D concentrations and mucosal inflammation as assessed by the Mayo endoscopy score (P = 0.01), disease activity as indicated by the total Mayo score (P = 0.001), and histologic activity (P = 0.02). A serum 25(OH)D concentration <20 ng/mL was associated with decreased mucosal transcript and protein expression concentrations of VDR, E-cadherin, and occludin as well as decreased protein expression of ZO-1, whereas TNF-α and IL-8 mucosal transcript expression concentrations were increased. CONCLUSIONS: In UC patients, serum 25(OH)D concentration is inversely correlated with mucosal inflammation and disease activity. These results, coupled with the findings that serum 25(OH)D concentrations correlate with the mucosal expression of VDR as well as epithelial junction proteins and inversely with proinflammatory cytokines, suggest that vitamin D deficiency may contribute to UC inflammation by disrupting epithelial barrier function.

The renin-angiotensin system mediates EGF receptor-vitamin d receptor cross-talk in colitis-associated colon cancer.

PURPOSE: We previously showed that EGF receptor (EGFR) promotes tumorigenesis in the azoxymethane/dextran sulfate sodium (AOM/DSS) model, whereas vitamin D suppresses tumorigenesis. EGFR-vitamin D receptor (VDR) interactions, however, are incompletely understood. Vitamin D inhibits the renin-angiotensin system (RAS), whereas RAS can activate EGFR. We aimed to elucidate EGFR-VDR cross-talk in colorectal carcinogenesis. EXPERIMENTAL DESIGN: To examine VDR-RAS interactions, we treated Vdr(+/+) and Vdr(-/-) mice with AOM/DSS. Effects of VDR on RAS and EGFR were examined by Western blotting, immunostaining, and real-time PCR. We also examined the effect of vitamin D3 on colonic RAS in Vdr(+/+) mice. EGFR regulation of VDR was examined in hypomorphic Egfr(Waved2) (Wa2) and Egfr(wild-type) mice. Angiotensin II (Ang II)-induced EGFR activation was studied in cell culture. RESULTS: Vdr deletion significantly increased tumorigenesis, activated EGFR and ß-catenin signaling, and increased colonic RAS components, including renin and angiotensin II. Dietary VD3 supplementation suppressed colonic renin. Renin was increased in human colon cancers. In studies in vitro, Ang II activated EGFR and stimulated colon cancer cell proliferation by an EGFR-mediated mechanism. Ang II also activated macrophages and colonic fibroblasts. Compared with tumors from Egfr(Waved2) mice, tumors from Egfr(wild-type) mice showed upregulated Snail1, a suppressor of VDR, and downregulated VDR. CONCLUSIONS: VDR suppresses the colonic RAS cascade, limits EGFR signals, and inhibits colitis-associated tumorigenesis, whereas EGFR increases Snail1 and downregulates VDR in colonic tumors. Taken together, these results uncover a RAS-dependent mechanism mediating EGFR and VDR cross-talk in colon cancer.