Konstantinos Oikonomou

Renal manifestations and complications of inflammatory bowel disease

Renal manifestations and complications are not rare in patients with inflammatory bowel disease (IBD) and may present as nephrolithiasis, amyloidosis, tubulointerstitial nephritis, and glomerulonephritis. Symptoms of renal impairment are not always specific and since the underlying bowel disease is preponderant, renal function deterioration may be underestimated. Additionally, medical treatment of patients with IBD such as aminosalicylates, cyclosporine, and tumor necrosis factor‐&agr; inhibitors can cause renal complications, although direct correlation to bowel disease is not always clear. The well‐documented renal manifestations and complications of IBD, as well as the possible renal side effects of new drugs, emphasize the need for periodic evaluation of renal function. New markers of renal function may facilitate early diagnosis and unravel the complex mechanisms responsible for kidney damage. The purpose of this review is to summarize the renal manifestations and complications as well as the markers of renal function utilized in IBD, attempting to shed more light on the pathophysiology of renal damage in IBD. (Inflamm Bowel Dis 2011;)

Angiogenin, angiopoietin-1, angiopoietin-2, and endostatin serum levels in inflammatory bowel disease.

Background: Angiogenesis is a complex process, involving a great number of mediators. It is implicated in the pathogenesis of numerous diseases, holding a critical role in inflammatory bowel disease (IBD). The objective of this study was to assess serum levels of angiogenin, angiopoietin‐1, angiopoietin‐2, and endostatin in IBD patients. Methods: Measurement of all angiogenesis mediators was performed with a commercially available enzyme‐linked immunosorbent assay. Fifty‐two patients with ulcerative colitis (UC), 59 with Crohns disease (CD), and 55 healthy controls (HC) were included in the study. The values were analyzed with regard to disease and patients characteristics. Results: Angiogenin levels were significantly higher in IBD patients compared to HC (P < 0.001) and in UC and CD smoker patients compared to nonsmokers (P = 0.0121 and P = 0.005, respectively). Angiogenin levels were lower in UC patients receiving 5‐aminosalicylate (5‐ASA) alone, compared to those receiving combined therapy (P = 0.0478). Angiopoietin‐1 levels were significantly lower in IBD patients compared to HC (P < 0.0001) and increased in smokers compared to nonsmoker UC patients (P = 0.0085). IBD patients demonstrated increased angiopoietin‐2 levels compared to HC (P = 0.0131), while CD patients with disease restricted to the colon had significantly lower levels compared to other disease locations (P < 0.0001). Higher endostatin levels were recorded in UC patients with extensive colitis. Conclusions: Elevated serum angiogenin and angiopoietin‐2 levels and lower serum angiopoietin‐1 levels were shown in IBD patients, as well as a different pattern of angiogenic factor alterations related to location, treatment, smoking habits and gender. Inflamm Bowel Dis 2011

Prevalence and Characteristics of Extra-intestinal Manifestations in a Large Cohort of Greek Patients with Inflammatory Bowel Disease

BACKGROUND AND AIMS Extraintestinal manifestations [EIMs] are common in inflammatory bowel disease [IBD]. Data on epidemiology and risk factors of EIMs in IBD patients are limited. The aim of this study was to investigate the prevalence of EIMs in a large cohort of Greek IBD patients and identify risk factors for their development. METHODS The study population consisted of IBD patients, who were followed in eight tertiary Greek hospitals. Demographic and clinical characteristics of patients were analysed. The diagnosis of EIMs was based on standard criteria and on specialist consultation. RESULTS In total, 1860 IBD patients (1001 with Crohns disease [CD], 859 with ulcerative colitis [UC]) were registered. Among them 615 [33.1%] exhibited at least one EIM; 238 patients [38.6%] developed an EIM before IBD diagnosis. An association between active IBD and presence of an EIM was established in 61.1% of the patients. Arthritic [peripheral arthritis], mucocutaneous [erythema nodosum], and ocular [episcleritis] were the most common manifestations. EIMs were more prevalent in females, patients with CD, smokers [for all p <0.0001], patients with extensive UC [p = 0.007], and patients with a previous appendectomy [p < 0.0001] or a major IBD-related surgery [p = 0.012]. CONCLUSIONS About one-third of Greek IBD patients developed at least one EIM. Of those, more than one-third had their EIM diagnosed before IBD, and in about two-thirds it was related to disease activity. EIMs were more frequently present in females and patients with extensive UC in multivariate analysis.

Downregulation of serum epidermal growth factor in patients with inflammatory bowel disease. Is there a link with mucosal damage

Background: Epidermal growth factor (EGF) is a multipotent peptide which contributes to epithelial development, inhibition of gastric acid secretion, acceleration of wound healing, and promotion of angiogenesis. The aim of this study is to evaluate serum EGF concentrations in inflammatory bowel disease (IBD) patients, with regard to disease and patients’ characteristics. Methods: EGF determination was performed by a commercially available enzyme-linked immunosorbent assay. Fifty-two patients with ulcerative colitis (UC), 59 with Crohns disease (CD), and 55 healthy controls (HC) were included in the study. Results: Mean ( ± SEM) serum EGF levels were 217.2 ( ± 30.40) pg/mL in UC patients, 324.6 ( ± 37.29) pg/mL in CD patients, and 453.1 ( ± 39.44) pg/mL in HC. Serum EGF levels were significantly lower in UC and CD patients compared to HC (P < 0.0001 and P = 0.0199, respectively). Lower serum EGF levels were observed in UC compared to CD patients (P = 0.0277). Extent of the disease was found to affect serum EGF levels in UC, demonstrating significant reduction in patients with left-sided colitis and pancolitis in comparison with those with proctitis (P = 0.0190 and P = 0.0024, respectively). EGF concentration was not influenced by other characteristics of patients and disease. Conclusions: Significantly, lower levels of serum EGF are observed in IBD patients compared to HC, while disease extent plays a key role in regulation of serum EGF in UC. Downregulation of serum EGF may be correlated with different patterns of bowel inflammation, epithelial development, and wound healing in IBD.

Drug-Induced Nephrotoxicity in Inflammatory Bowel Disease

Conservative management of inflammatory bowel disease (IBD) is based on a combination of drugs, including aminosalicylates (ASAs), steroids, antibiotics, immunosuppressives and biologic agents. Although various side effects have been related to treatment regimens, drug-induced nephrotoxicity is rather uncommon. Furthermore, it is often underestimated since renal function deterioration may be attributed to the underlying disease. The nephrotoxicity of ASAs and cyclosporine A seems well established, but recent data have suggested a possible role of biologic agents such as infliximab and adalimubab in renal impairment. The aim of this review is to summarize the nephrotoxic effects of medical treatment as well as to express possible caveats in the administration of novel agents in IBD.

Liver cirrhosis-effect on QT interval and cardiac autonomic nervous system activity

AIM To examine the impact of liver cirrhosis on QT interval and cardiac autonomic neuropathy (CAN). METHODS A total of 51 patients with cirrhosis and 51 controls were examined. Standard 12-lead electrocardiogram recordings were obtained and QT as well as corrected QT interval (QTc) and their dispersions (dQT, dQTc) were measured and calculated using a computer-based program. The diagnosis of CAN was based upon the battery of the tests proposed by Ewing and Clarke and the consensus statements of the American Diabetes Association. CAN was diagnosed when two out of the four classical Ewing tests were abnormal. RESULTS QT, QTc and their dispersions were significantly longer (P < 0.01) in patients with cirrhosis than in controls. No significant differences in QT interval were found among the subgroups according to the etiology of cirrhosis. Multivariate regression analysis after controlling for age, gender and duration of cirrhosis demonstrated significant association between QT and presence of diabetes mellitus [standardized regression coefficient (beta) = 0.45, P = 0.02] and treatment with diuretics (beta = 0.55, P = 0.03), but not with the Child-Pugh score (P = 0.54). Prevalence of CAN was common (54.9%) among patients with cirrhosis and its severity was associated with the Child-Pugh score (r = 0.33, P = 0.02). Moreover, patients with decompensated cirrhosis had more severe CAN that those with compensated cirrhosis (P = 0.03). No significant association was found between severity of CAN and QT interval duration. CONCLUSION Patients with cirrhosis have QT prolongation. Treatment with diuretics is associated with longer QT. CAN is common in patients with cirrhosis and its severity is associated with severity of the disease.

Laparoendoscopic rendezvous may be an effective alternative to a failed preoperative endoscopic retrograde cholangiopancreatography in patients with cholecystocholedocholithiasis

Background: Endoscopic retrograde cholangiopancreatography (ERCP), followed by laparoscopic cholecystectomy (LC), remains the standard way of management for patients with cholecystocholedocholithiasis. Laparoendoscopic rendezvous (LERV), a combined procedure for removing the gallbladder laparoscopically and clearing the common bile duct (CBD) endoscopically at the same time, could be an attractive alternative. The aim of this study was to compare LERV with classic ERCP in patients with cholecystocholedocholithiasis. Methods: 886 patients with cholecystocholedocholithiasis were treated either with the LERV technique (90 patients), or with the 2-stage approach, which includes preoperative ERCP followed by LC (796 patients). The primary endpoint was any difference in the success of CBD cannulation and clearance; secondary endpoints were the detection of differences in morbidity (especially post-ERCP pancreatitis [PEP]), and the feasibility of the two approaches. Results: Successful cannulation of the CBD was more frequent with conventional ERCP compared with the LERV technique (89.8% vs. 75.5%, P=0.0001). LERV appears to be as effective as conventional ERCP for complete CBD clearance (85.5% vs. 82.8%, P<0.1). None of the patients in the LERV group had an episode of clinical PEP, whereas in the conventional ERCP group there were 23 episodes of PEP and one death. The median amylase level was higher in patients undergoing conventional ERCP group compared to patients in LERV group. Conclusion: Classic ERCP has a higher rate of successful CBD cannulation and a similar rate of CBD clearance compared to LERV.

P604 Prevalence and characteristics of dermatologic manifestations in a Greek population of inflammatory bowel disease patients followed-up in tertiary centers

psoriasis aimed to study the incidence of these diseases over 2 years). Methods: Patients aged 18 years-old with known or newly diagnosed SpA, IBD or psoriasis were recruited from rheumatology, IBD and dermatology offices from 15 hospitals. Clinical data were collected through direct interview and patient’s clinical record review. Results: The SpA cohort (mean age 48 years, men: 63%) comprised 601 patients with the following diagnoses: ankylosing spondylitis (55.1%), psoriatic arthritis (25.1%), undifferentiated SpA (16.1%), enteropathic arthritis (2.5%), others (1.3%). The prevalence of IBD (table) was 5.1% (95%CI: 3.7 7.2), and the specific diagnoses were Crohn’s disease (3.0%, 95%CI: 1.9 4.7), ulcerative colitis (1.0%, 95%CI: 0.5 2.2), and undifferentiated colitis (1.2%, 95%CI 0.6 2.4). The prevalence of IBD was 100% in those with enteropathic arthritis and upon removal of these patients, the prevalence of IBD in other SpA patients was 2.7% (95%CI: 1.7 4.4), with figures of 3.9%, 0.7% and 2.4% in patients with ankylosing spondylitis, psoriatic arthritis or undifferentiated SpA, respectively. The prevalence was similar in men and women (5.0% and 5.4%, p =NS), and in those with or without other extra-articular manifestations of SpA (4.9% and 6.7%, p =NS). It was slightly higher in those with SpA of longer duration (3.5%, 4.4% and 6.9% respectively for those with SpA of 8 years duration, P=NS), and in those without family history of SpA (6.4% versus 1.7%, p = 0.048). The multivariate analysis identified the absence of family history of SpA as the only variable associated to the presence of IBD (3.9 [95%CI: 1.1 16.7]). The psoriasis cohort comprised 528 patients, and only 7 had IBD (prevalence 1.3%, 95%CI: 0.6 2.7).

P144 Urinary NGAL: A reliable marker of minor tubular injury in inflammatory bowel disease

Blood test (FOBt) followed by a screening colonoscopy if FOBt positive. Our study aimed to quantify the incidental diagnosis of Inflammatory Bowel Disease (IBD) through this programme and characterise patient outcome in this cohort. Methods: We conducted a retrospective review of BCSP outcomes at our Centre from its launch in April 2008 until September 2011. Screening data included the number of patients invited to participate, number screened (FOBt outcome “normal” or “abnormal”) and number of colonoscopies performed. In those with newly diagnosed IBD at colonoscopy confirmed on histology, clinical data including demographics, disease characteristics, previous therapy and outcome were obtained from case note and electronic patient record review. Results: Of 136,811 patients invited, 67,485 were screened, representing an uptake of 49.33% and FOBt positivity of 2.02%. Colonoscopy was performed in 1401 patients (female 523). Polyps were detected in 630 (41.37%), cancer in 134 (8.80%) and 469 (30.79%) had a normal examination. Thirty patients had endoscopic appearance suggestive of IBD, confirmed at histology in 15 patients. Two patients were excluded from analysis as the diagnosis of colitis preceded the screening examination on case note review. Three of 13 incidental IBD cases reviewed were female, median age at diagnosis was 65 and mean follow-up was 29.8 months. Five patients had Crohn’s disease, 6 ulcerative colitis and 2 had IBD-type unclassified (IBDU). Seven patients (53.8%) were asymptomatic at diagnosis. Treatment included steroids (6), 5-ASA (11), immunomodulators (azathioprine 4; methotrexate 1) and anti-TNF (infliximab 2). No patient required surgery. Those requiring immunomodulators and/or infliximab were all male and had asymptomatic pan ulcerative colitis, symptomatic left sided ulcerative colitis, symptomatic left-sided IBDU colitis and symptomatic colonic, non-stricturing, non-penetrating Crohn’s disease at diagnosis. Conclusions: An incidental diagnosis of IBD is not an uncommon occurrence. With the advent of endoscopic bowel cancer screening this number is probably set to increase. This subset of patients may present an important model for study of early disease providing novel insights into disease pathogenesis and evolving treatment paradigms.