Miodrag Krstic

Nutritional status in patients with active inflammatory bowel disease: Prevalence of malnutrition and methods for routine nutritional assessment

BACKGROUND AND AIM Malnutrition is a common feature of inflammatory bowel disease (IBD). There are numerous methods for the assessment of nutritional status, but the gold standard has not yet been established. The aims of the study were to estimate the prevalence of undernutrition and to evaluate methods for routine nutritional assessment of active IBD patients. MATERIAL AND METHODS Twenty-three patients with active Crohn disease, 53 patients with active ulcerative colitis and 30 controls were included in the study. The nutritional status was assessed by extensive anthropometric measurements, percentage of weight loss in the past 1-6 months and biochemical markers of nutrition. RESULTS All investigated nutritional parameters were significantly different in IBD patients compared to control subjects, except MCV, tryglicerides and serum total protein level. Serum albumin level and body mass index (BMI) were the most predictive parameters of malnutrition. According to different assessment methods the prevalence of undernutrition and severe undernutrition in patients with active IBD were 25.0%-69.7% and 1.3%-31.6%, respectively, while in the control subjects no abnormalities have been detected. There was no statistically significant difference of nutritional parameters between UC and CD patients except lower mid-arm muscle circumference in UC group. CONCLUSIONS Malnutrition is common in IBD patients. BMI and serum albumin are simple and convenient methods for the assessment of the nutritional status in IBD patients. Further studies with larger group of patients are necessary to elucidate the prevalence of malnutrition and the most accurate assessment methods in IBD patients.

Complications of Peptic Ulcer Disease

There are four major complications of peptic ulcer disease (PUD): bleeding, perforation, penetration, and obstruction. Complications can occur in patients with peptic ulcer of any etiology. Despite improvements in the medical management and the lower overall incidence of PUD, there are conflicting data about the incidence of potentially life-threatening ulcer complications. There are important time trends embedded within this stable overall rate of complications: the dramatic decline in the prevalence of Helicobacter pylori (comparing the cohort born from 1900 to 1920 to cohorts born after 1940); an increased use of nonsteroidal anti-inflammatory drugs, and an increased rate of ulcer complications related to such drug use, especially in the elderly. As a result of these trends, ulcer complications are on the rise in older patients but on the decline in younger individuals. Hemorrhage is the most frequent PUD complication and its incidence is increasing in comparison to perforation and stenosis. Therapeutic endoscopy is considered the treatment of choice for bleeding ulcers, reducing the need for emergent surgical procedures to 10–20% of the cases. In recent years, besides the success of angiographic embolization, the containment of massive hemorrhage must also be taken into account. Transcatheter arterial embolization is also an effective and safe treatment in patients with duodenal ulcers re-bleeding after therapeutic endoscopy or surgery.

Extraintestinal Manifestations of Autoimmune Pancreatitis

The term autoimmune pancreatitis (AIP) was first used in Japan in 1995 to describe a newly recognized form of chronic pancreatitis, after the description of Yoshida and colleagues. But Sarles in 1961, first described a form of idiopathic chronic inflammatory sclerosis of the pancreas, suspected to be due to an autoimmune process. AIP has become a widely accepted term because clinical, serologic, histologic, and immunohistochemical findings suggest an autoimmune mechanism. Most affected patients have hypergammaglobulinemia and increased serum levels of IgG, particularly IgG4. Recently published International Consensus Diagnostic Criteria for Autoimmune Pancreatitis include Guidelines of the International Association of Pancreatology, classifying AIP into types 1 and 2, using five cardinal features of AIP, namely imaging of pancreatic parenchyma and duct, serology, other organ involvement, pancreatic histology, and an optional criterion of response to steroid therapy. Extrapancreatic presentations can include sclerosing cholangitis, retroperitoneal fibrosis, sclerosing sialadenitis (Küttner tumor), lymphadenopathy, nephritis, and interstitial pneumonia. Increased IgG4+ plasma cell infiltrate has been reported in sclerosing lesions from other organ sites, including inflammatory pseudotumors of the liver, breast, mediastinum, orbit, and aorta, and it has been observed with hypophysitis and IgG4-associated prostatitis. Abundant IgG4+ plasma cells were also confirmed in Riedel thyroiditis, sclerosing mesenteritis, and inflammatory pseudotumor of the orbit and stomach. Extrapancreatic lesions could be synchronously or metachronously diagnosed with AIP, sharing the same pathological conditions, showing also a favorable result to corticosteroid therapy and distinct differentiation between IgG4-related diseases from the inherent lesions of the corresponding organs.

Classification of Chronic Pancreatitis

Chronic pancreatitis (CP), defined as a continuing inflammatory disease of the pancreas characterized by irreversible morphological changes which typically cause abdominal pain and/or permanent impairment of pancreatic function, has proved resistant to categorization. The disease may present clinically either with an individual symptom or a combination of symptoms associated with loss of pancreatic function. The single most frequent symptom of CP is pain, either in the form of intermittent episodes or in a more chronic or persistent pattern. The natural history of CP is usually characterized by progression of tissue damage and various degrees of exocrine and endocrine pancreatic insufficiency, which will become apparent over time. The main reason for the lack of guided strategies in the therapeutic management of CP is the absence of a clinically applicable classification of CP. In the past, several classifications have certainly contributed to a better understanding of the pathogenesis and pathophysiology of CP. The meetings in Marseilles (1963 and 1984), Cambridge (1984) and in Rome (1985) added a great deal of information to our knowledge of the pathogenesis and evolution of CP. More recent work on understanding the temporal course of CP led to the Zurich international classification which has been used to define patient cohorts in recent studies of patients undergoing surgery for CP. In order to combine clinical experience in the field of CP with progress in diagnostic methods and new molecular technologies for the assessment of CP, a classification of CP based on key clinical aspects is crucial. A new classification should first be validated to determine whether it can be applied to the majority of patients with CP, and then the value of such a classification needs to be tested in our understanding of the natural course in different etiologies (progression, arrest, regression) and most importantly, to study the clinical outcome when different therapeutic strategies are applied.

CARD15 gene polymorphisms in Serbian patients with Crohn's disease : genotype-phenotype analysis

Objective Genetic heterogeneity and incomplete phenotype penetrance complicate genetic analysis of Crohns disease (CD). Studies in western Europe have shown that CARD15 polymorphisms increase susceptibility to CD, but frequencies vary within different European populations. The aim here was to evaluate the prevalence of CARD15 mutations and their phenotypic correlation in a Serbian population. Materials and methods 131 patients with CD, 65 patients with ulcerative colitis, and 88 healthy controls were genotyped for three common mutations (R702W, G908R, Leu1007insC) by PCR-restriction fragment length polymorphism. χ2 and Students t-test were used for statistical assessment. Results At least one CARD15 disease-associated allele was found in 35.11% patients with CD, 14.77% of healthy controls (P=0.001), and 7.69% patients with ulcerative colitis (P=0.0001). The L1007fs mutation showed a significant association with CD (P<0.0001). The frequency of R702W mutant allele was almost equal in the control group and CD patients Univariate analyses established that CARD15 carriers had a significantly higher risk of isolated ileal location [P=0.042; odds ratio (OR) 2.30; 95% confidence interval (CI): 1.02–5.19], fibrostenotic behavior (P<0.0001; OR 9.86; 95% CI: 4.29–22.62), surgical resection (P=0.036; OR 2.2; CI, 1.046–4.626), and earlier onset of disease (P=0.026). Conclusion This study confirms that CARD15 carriers, especially L1007fs mutants, in central Europeans have an increased risk of CD and it is associated with earlier onset, ileal, fibrostenotic disease and a higher risk of surgery. Any influence of latitude is not matched by an east–west divide on the genotype frequency and phenotype of CD within Europe.

Cystic Dystrophy in Heterotopic Pancreas of the Duodenal Wall

Background: Cystic dystrophy in heterotopic pancreas (CDHP) is a rare condition. It has been recently reported as one of the etiologic obstructive factors of chronic pancreatitis. The aim of our study was to evaluate diagnosis and management of CDHP in the duodenal wall in a surgical series. Methods: We retrospectively reviewed 13 patients with available clinical data. Results: There were 11 male and 2 female patients, median age 42 years. The average duration of symptoms was 7.5 months. 6 of them (46%) were alcoholics, and 10 (75%) had signs of chronic pancreatitis. Almost all of them (12/13; 92%) revealed disabling pain, while 4 (31%) had associated jaundice. In 4 of 7 patients (57%), weight loss was observed. Most often the patients were suspected of having pancreatic head mass with or without signs of chronic pancreatitis. All patients underwent surgical treatment. Pathological examination showed the presence of cysts surrounded by inflammation and fibrosis in the duodenal wall, as well as the presence of chronic pancreatitis in the pancreas proper. Conclusions: Cystic dystrophy of the duodenal wall represents a significant proportion of patients undergoing surgery for chronic pancreatitis. Pancreatoduodenectomy is the best therapeutic option.

Endoscopic Ultrasound for Differential Diagnosis of Duodenal Lesions

PURPOSE Duodenal tumors are rare and require a different management from that of esophagogastric neoplasia. The present study retrospectively analyses the endoscopic ultrasound (EUS) features of duodenal tumors of both epithelial and subepithelial origin. MATERIALS AND METHODS During a 12 year period, all duodenal tumors with histologic confirmation by surgery or biopsy were collected including endoscopic and endosonographic images. EUS images were analyzed for specific features (echogenicity, wall layer structure and relation, outer margins) to possibly distinguish epithelial (polyps and carcinoma versus lymphoma) and subepithelial (tumor type) tumors. RESULTS 53/80 cases had histologic confirmation (mean age 53.1 ± 11.4 years, m:f = 33:20), 31 were epithelial (13 adenomas, 12 carcinomas, 6 lymphomas) and 22 subepithelial (11 GISTs, 7 Brunneromas, 1 lipoma, 3 NETs). EUS did not recognize carcinomas in 2/13 adenomas. EUS features suggesting carcinoma were loss of wall layers and irregular margins. 5/6 lymphomas showed inhomogeneous thickening with layers partially recognizable. Tumor type of subepithelial lesions correlated with echogenicity: GIST tumors were mostly (62.5 %) hypocheoic with the 3 malignant cases being characterized by heterogeneous echopattern with irregular outer margins. Of the hyperechoic lesions, lipomas had a homogeneous whitish appearance, while NET and Brunneromas were less hyperechoic. In the latter, the endoscopic aspect was also helpful for differential diagnosis. Accuracy of combined endoscopic/EUS imaging for all duodenal lesions was 84.9 % (45/53). No procedural complications occurred among all patients that received EUS examinations. CONCLUSION EUS contributes to the differential diagnosis of epithelial lesions known to be malignant; in subepithelial tumors, tissue confirmation is still required.

Epidemiological Trends in Stomach-Related Diseases

Epidemiology is a study of disease variations by geography, population demographics and time. Temporal influences can manifest themselves as age effects, period effects, cohort effects, seasonal or monthly variations. The acquisition of Helicobacter pylori infection during early childhood and the ensuing risk for the future development of peptic ulcer or gastric cancer represents a typical example for a cohort effect in digestive diseases. The incidence and prevalence of uncomplicated peptic ulcer have decreased in recent years, largely because of the availability of treatment to eradicate H. pylori and the decreasing prevalence of H. pylori infection. Nowadays, gastric and duodenal ulcers tend to occur in older people, who were more likely to have been exposed to H. pylori in their childhood than recently born generations. The overall incidence of gastric cancers is declining; however, there has been a relative increase in the incidence of tumors of the esophagogastric junction and gastric cardia. Thus, by extrapolating the strong, stable and consistent mortality rate declines in recent decades, gastric cancer was projected to become increasingly less important as a cause of death in Europe in the next decades.

The Polymorphism rs3024505 (C/T) Downstream of the IL10 Gene Is Associated with Crohn’s Disease in Serbian Patients with Inflammatory Bowel Disease

Inflammatory bowel disease (IBD), manifesting as Crohns disease (CD) and ulcerative colitis (UC), is characterized by recurring episodes of inflammation in gastrointestinal tract, in which aberrant production of regulatory cytokine interleukin-10 (IL-10) presumably plays important role. Single nucleotide polymorphisms (SNPs) that affect IL-10 production, such as rs1800896 (G/A) at position -1082 and rs1800871 (C/T) at position -819 in the promoter region of the IL10 gene, have been associated with CD and/or UC, but the results were inconsistent. Another SNP that may alter IL-10 production, rs3024505 (C/T) located immediately downstream of the IL10 gene has been recently identified. T allele of rs3024505 was associated with both UC and CD in Western populations, but the studies from East European countries are lacking. Therefore, our aim was to assess the association of rs3024505, rs1800896 and rs1800871 with Serbian IBD patients. To this end, 107 CD and 99 UC patients and 255 healthy controls were genotyped. As a result, T allele of rs3024505 was associated with CD at allelic, genotypic (GT genotype) and haplotypic (GCCT haplotype) level, suggesting potential role of this variant in susceptibility to CD. In contrast, CD patients carrying C allele of rs3024505 had significantly increased risk of anemia and stricturing/penetrating behavior. No association was observed between rs3024505 and UC or SNPs in IL10 promoter region and any form of IBD. In conclusion, rs3024505 SNP flanking the IL10 gene is associated with susceptibility and severity of disease in Serbian CD patients, further validating its role as a potential biomarker in IBD.

Capsule endoscopy is useful diagnostic tool for diagnosing Meckel's diverticulum.

Objective Meckel’s diverticulum (MD) is the most common congenital anomaly of the gastrointestinal tract. Although a majority of patients remain asymptomatic, complications may occur in a subset of patients. MD is a rare cause of gastrointestinal bleeding (GIB) in adults. We aimed to clarify the possible role of capsule endoscopy (CE) in the identification of Meckel’s diverticulum. Patients and methods From October 2004 to December 2010, 157 CEs were performed (83 male individuals, mean age 51±20 years; range 3–83 years) for obscure GIB. Before CE, all patients underwent nonconclusive upper and lower endoscopy at least two times and barium follow-through. Results CE identified the source of bleeding in 70/157 patients (44.6%). MD was diagnosed in 13/70 (18.6%) patients (11 male individuals, mean age 35±20 years, range, 3–69 years) after CE. Nine patients presented with obscure overt and four with obscure occult bleeding. The mean duration of obscure GIB history was 13 months (range 1–72 months). The mean hemoglobin concentration at the time of the procedure was 115±12 g/l. The findings of MD on CE were double lumen sign (13/13), visible blood (7/13), and diaphragm sign (6/13). All patients were operated upon, and MD histologically verified in 11. In two patients CE was false-positive and in two patients, false-negative. Capsule endoscopy had a positive predictive value of 84.6% for the diagnosis of MD. Conclusion MD should be considered in the differential diagnosis of obscure GIB in adults. CE is an effective and promising modality for diagnosing MD in patients with obscure GIB.