[Complete and sustained remission of liver metastases from neuroendocrine tumor with somatostatin analogue therapy]. / Neuroendokrin daganat májmetasztázisainak teljes és tartós remissziója szomatosztatinanalóg-kezelés hatására.

Somatostatin analogues represent a major treatment modality in the therapy of neuroendocrine tumors. Their efficacy is well documented in the inhibition of hormone secretion; however, novel data seem to underline their effectiveness in tumor regression, as well. In this report authors present a case of type 1 neuroendocrine tumors of the stomach associated with liver metastases. Somatostatin analogue treatment resulted in a complete regression of the primary tumor and the metastases within two years. This case draws attention on the importance of somatostatin analogue treatment not only in the control of hormonal symptoms but also in the inhibition of tumor growth.

Effect of proton-pump inhibitor therapy on serum chromogranin a level.

BACKGROUND: The neuroendocrine marker, chromogranin A (CgA) increases during medium- or long-term proton-pump inhibitor (PPI) treatment. AIMS: To analyze the effect of ultra-short-term and diverse dose of PPI therapy on serum CgA and gastrin levels and evaluate the effect of PPI treatment cessation. PATIENTS AND METHODS: Fasting serum CgA and gastrin were determined in newly diagnosed gastroesophageal reflux disease (GERD) patients (n = 54) treated with diverse doses of PPI during a 28-day period, in patients treated with PPIs for at least 6 months (n = 42), and in subjects where PPI treatment could be stopped (n = 11). RESULTS: A significant stepwise increase of CgA levels was observed after 5 days during the 28-day period treatment with all PPI doses. Gastrin increased significantly also in the standard and high-dose PPI subgroups. The most prominent increase of CgA was observed in the high-dose PPI subgroup. Serum CgA and gastrin were markedly elevated after 6 months of PPI treatment, and decreased significantly after 5 days of PPI discontinuation. CONCLUSIONS: Serum CgA increases significantly even after ultra-short-term (5 days) PPI therapy. After long-term treatment, 5-day cessation of PPI therapy is sufficient to decrease significantly both CgA and gastrin levels.

[Carcinoid tumors]. / Carcinoid daganatok.

The authors review the most important clinical aspects of carcinoid tumors. Carcinoid tumors originating in neuroendocrine cells are rare, usually slowly-growing neoplasms, however, they may present as aggressive and rapidly progressing tumors. Epidemiologic data indicates that their prevalence is gradually increasing, which may be explained, at least in part, by the development and wider use of advanced diagnostic methods. A considerable proportion of patients with neuroendocrine tumors are symptom-free, whereas others may have carcinoid syndrome or symptoms of other endocrine syndromes. Early diagnosis may be established by the measurement of biochemical markers (serum chromogranin A, urinary 5-hydroxyindoleacetic acid) and advanced localization methods. A considerable number of patients are diagnosed at the late stages of the disease; in these cases surgical cure is not possible but surgical and/or interventional radiologic procedures which reduce tumoral mass should be still considered. The most effective drugs for symptomatic treatment of carcinoid tumors are somatostatin analogues; in addition to their beneficial effect on clinical symptoms they may stabilize tumor growth for many years and, less frequently, may produce tumor regression. The use of chemotherapeutic agents is considered in patients with aggressive, rapidly growing and advanced tumors; initial findings with temozolomide and thalidomide in clinical trials raise the possibility that these chemotherapeutic agents may prove to be new therapeutic options. Radioisotope-labeled peptide receptor therapy with 131 I-MIBG, 90 Y-DOTA-TOC or 177 Lu-DOTA-TOC may offer a highly effective option for patients with progressive and advanced stage of neuroendocrine tumors. Initial observations obtained in clinical trials with some tyrosine kinase inhibitors, antibodies against tyrosine kinases, and with inhibitors of mammalian target of rapamycin (mTOR) support the possibility that at least some of these new agents may have a role in future treatment options in patients with advanced neuroendocrine tumors.

[Novel aspects in the pathogenesis of gastroesophageal reflux disease]. / A gastrooesophagealis refluxbetegség keletkezésének újabb szempontjai.

UNLABELLED: In addition to lower esophageal sphincter (LES) relaxations and decreased LES tone, increased intra-abdominal pressure can also play role in the pathogenesis of gastroesophageal reflux disease (GERD),. AIM: To analyze the correlation between occupation-related increased intra-abdominal pressure or straining (experienced for years) and the prevalence of GERD symptoms. METHODS: Reflux symptoms were analyzed through a questionnaire among professional singers, wind players and glassblowers in comparison with controls. RESULTS: Heartburn, regurgitation and hoarseness were significantly more frequent among professional singers than in controls (P<0.001). Among wind players heartburn (P<0.05) and regurgitation (P<0.01), among glassblowers regurgitation (P<0.01) were significantly more frequent in comparison with control subjects. Reflux symptoms correlated significantly with the duration of professional activity (P<0.05). CONCLUSIONS: Results suggest that reflux symptoms are more frequent among subjects with occupation-related increased intra-abdominal pressure. GERD seems to be a work-related disease in this aspect.

Comparison of the effects of 1,25 dihydroxyvitamin D and 25 hydroxyvitamin D on bone pathology and disease activity in Crohn's disease patients.

BACKGROUND: Vitamin D is essential for osteopenia therapy in Crohn's disease (CD). The active form of vitamin-D (aVD) is the 1,25(OH)2D. There are no data available whether aVD or plain vitamin-D (pVD) has any advantage in managing osteoporosis in CD or has any effect on the activity of the disease itself. Our work is a prospective study to compare the effects of aVD and pVD on bone metabolism and the clinical course of CD. METHODS: In all, 37 inactive CD patients were involved in the study and divided into 2 age-, gender-, and t-score-matched groups. Group A was treated with aVD while group B received pVD. Osteocalcin, beta-CrossLaps, osteoprotegerin, and receptor activator nuclear factor kappa-B ligand concentrations were estimated at the start of the study and at 6 weeks and 3 and 12 months. The activity of CD was also measured clinically and by laboratory parameters. RESULTS: At week 6 the Crohn's Disease Activity Index (CDAI) scores and concentration of C-reactive protein decreased (69.44 +/- 58.6 versus 57.0 +/- 54.89 and 15.8 +/- 23.57 mmol/L versus 7.81 +/- 3.91 mmol/L, respectively, P < 0.05) parallel with markers of bone turnover (beta-CrossLaps: 0.46 +/- 0.21 ng/mL versus 0.40 +/- 0.25 ng/mL, and osteocalcin: 32.29 +/- 15.3 ng/mL versus 29.98 +/- 14.14 ng/mL, P < 0.05); however, osteoprotegerin concentration (marker of osteoblast activity) increased (3.96 +/- 2.1 pg/mL versus 4.58 +/- 2.19 pg/mL) in group A, but did not change in group B. Osteocalcin and beta-CrossLaps concentrations changed more significantly by the 3rd month; however, these changes disappeared by the 12th month. CONCLUSIONS: According to our study, aVD has a more prominent short-term beneficial effect on bone metabolism and disease activity in CD compared with pVD.

Diagnosis and recognition of early esophageal neoplasia.

Barrett's esophagus (BE) is the precursor lesion of esophageal adenocarcinoma, a malignancy with increasing incidence in Western countries. Malignant transformation of Barrett's metaplasia is a multistep process in which intestinal metaplasia progresses through low-grade and high-grade dysplasia into eventually invasive cancer. Several risk factors for the development of BE have been identified. The degree of dysplasia is currently used as the most important marker of risk progression. The exact incidence of progression from BE to esophageal adenocarcinoma is unknown. Endoscopic surveillance and follow-up are advised in order to detect adenocarcinoma and its precursor precancerous lesions at an early and curable stage, although there has been much debate on this topic. New endoscopic imaging techniques may improve the detection of relevant precancerous lesions and early neoplasia. The use of biomarkers may enable identification of patients at risk for malignant progression.

Peptic esophageal stricture: medical treatment.

Peptic esophageal stricture as a consequence of gastroesophageal reflux disease is the most frequent among benign esophageal strictures. The incidence is low and has been decreasing since the 1990s with a parallel increase in proton pump inhibitor use. Dysphagia is a common symptom: accurate diagnostic procedures (barium esophagogram, upper endoscopy with biopsies) have to be performed to exclude malignant causes first. Medical (acid-suppressive) therapy, endoscopic dilation and surgical intervention are the main therapeutic options. Based on the results of randomized and observational studies evaluating the effect of acid-suppressive therapy on peptic stricture outcome, healing the coexistent esophagitis seems to be essential. Effective acid-suppressive therapy with proton pump inhibitors may reduce the need for repeated dilations and provide symptom relief and better clinical outcome. In refractory strictures, local steroid injection is likely beneficial.

Gastroesophageal reflux disease: work-related disease?

BACKGROUND: An occupation-related susceptibility of professional singers to experience gastroesophageal reflux has been suggested. AIMS: To investigate the prevalence of gastroesophageal reflux symptoms in a series of professional opera choristers, wind players, glassblowers and water polo players in comparison with a sample of general population. SUBJECTS AND METHODS: A total of 202 professional opera choristers from well-known choirs in different Hungarian regions, 71 professional wind players, 43 glassblowers, 54 water polo players were identified and 115 control subjects were compared prospectively. Reflux symptoms together with selected individual characteristics and lifestyle habits were investigated in study groups through a reflux questionnaire. RESULTS: Professional opera choristers reported a statistically significantly higher prevalence of heartburn, regurgitation and hoarseness than control subjects (p < 0.001). Among professional wind players, heartburn and regurgitation were significantly more frequent compared with controls (p < 0.05 and p < 0.01, respectively). Glassblowers reported a significantly higher prevalence of acid regurgitation in comparison with controls (p < 0.01). The prevalence of reflux symptoms in water polo players was similar to that of controls. In opera choristers, wind players and glassblowers, reflux symptoms appeared to be significantly correlated with the cumulative lifetime duration of professional singing, playing and working activity, respectively (p < 0.05). CONCLUSIONS: Our results demonstrate that professional opera choristers, professional wind players and glassblowers have a higher prevalence of reflux symptoms compared with control subjects. Gastroesophageal reflux in these professions should be considered as a work-related disorder that may have an impact on quality of life and may negatively interfere with professional performance.

Increased p53 expression in the malignant transformation of Barrett's esophagus is accompanied by an upward shift of the proliferative compartment.

Neoplastic progression in Barrett's esophagus (BE) occurs by a multistep process associated with early molecular and morphological changes. This study evaluated cell proliferation and p53 expression and their correlation in the development and progression of esophageal adenocarcinoma. PCNA and p53 expressions were analyzed in biopsy samples by immunohistochemistry including patients with reflux esophagitis, BE, BE with concomitant esophagitis, Barrett's dysplasia, esophageal adenocarcinoma and a control group without any histological changes. Progressive increase in cell proliferation and p53 expression was found in the sequence of malignant transformation of the esophageal mucosa. While cell proliferation was significantly lower in the control group compared with all other groups, there was no increase in p53 expression of esophageal tissues that were negative for dysplasia. Dysplastic BE tissues revealed significantly higher cell proliferation and p53 expression levels compared to BE, reflux esophagitis or BE with concomitant esophagitis. Both, cell proliferation and p53 expression were significantly higher in adenocarcinoma compared to BE or Barrett's dysplasia. Interestingly, while just BE with concomitant esophagitis showed significantly higher p53 expression levels than BE, both, BE with concomitant esophagitis and reflux esophagitis revealed significantly higher cell proliferation levels compared to BE. Alterations of cell proliferation and p53 expression showed a strong correlation. Simultaneous activation of cell proliferation and p53 expression strongly suggest their association with esophageal epithelial tumor genesis and particularly, their specific role in the biology of esophageal adenocarcinoma. Quantification of these parameters in BE is thought to be useful to identify patients at higher risk for progression to adenocarcinoma.

[Bowel gases]. / A bélgázok jelentosége.

Abdominal bloating is one of the most common symptoms in patients with different gastrointestinal disorders. The majority of patients usually attribute this complaint to increased intestinal gas volume. Recent experimental studies using the gas challenge test help us to better understand the gas dynamics and tolerance in humans. Although there are some clinical conditions that are clearly related to impaired gas dynamics, the role of gases in functional gastrointestinal disorders especially in irritable bowel syndrome is much more complicated. Impaired gas handling, abnormal reflexes and visceral hypersensitivity seem to be the main factors resulting in abdominal bloating in this group of patients. Further clinical studies are needed to clarify the pathophysiologic mechanisms of intestinal gas and this may contribute to the evaluation of optimal therapy.

[Novel therapeutic approaches in the treatment of irritable bowel syndrome]. / Az irritábilis bélszindróma kezelésének új lehetoségei.

The treatment of irritable bowel syndrome due to the heterogeneous clinical symptoms and coexisting psychiatric disorders is still controversial. Although several agents with different mechanisms of action are widely used in clinical practice, there are only few drugs available with strong evidence of their efficacy, safety and tolerability at present. The etiology of irritable bowel syndrome is considered to be multifactorial: experimental and clinical research on visceral hypersensitivity, motility and brain-gut axis involving its neurotransmitters and receptors created the foundation of novel therapeutic approaches. Albeit nowadays several drugs (alosetron, tegaserod) have been registered in a few countries for the treatment of irritable bowel syndrome, further large clinical trials are required related to the new chemical entities.

Alterations of glutathione S-transferase and matrix metalloproteinase-9 expressions are early events in esophageal carcinogenesis.

AIM: To investigate the role of glutathione S-transferase (GST) and matrix metalloproteinase-9 (MMP-9) expressions in the development and progression of reflux esophagitis-Barrett's metaplasia-dysplasia-adenocarcinoma sequence in the esophagus. METHODS: GST and MMP-9 expressions were analyzed in 51 paraffin-embedded tissue samples by immunohistochemistry including patients with reflux esophagitis (n = 7), Barrett's metaplasia (n = 14), Barrett and esophagitis (n = 8), Barrett and dysplasia (n = 7), esophageal adenocarcinoma (n = 8) and a control group without any histological changes (n = 7). Immunostaining was determined semiquantitatively. Statistical analysis with one-way ANOVA, LSD test and correlation analysis were performed. P value of < 0.05 was considered significant. RESULTS: GST expression was significantly higher while MMP-9 expression was significantly lower in control group compared to Barrett's metaplasia and the other groups. No major changes were observed between Barrett, esophagitis, and Barrett and concomitant esophagitis. Barrett and concomitant dysplasia, and adenocarcinoma revealed a significant lower expression of GST and higher levels of MMP-9 compared to all other groups. Adenocarcinoma showed almost no expression of GST and significantly higher levels of MMP-9 than Barrett and concomitant dysplasia. Alterations of GST and MMP-9 were inversely correlated (r = -0.82). CONCLUSION: Decreased GST and increased expression of MMP-9 in Barrett's metaplasia-dysplasia-adenocarcinoma sequence as compared to normal tissue suggest their association with esophageal tumorigenesis. Loss of GST and gain of MMP-9 in Barrett with dysplasia compared to non-dysplastic metaplasia indicate that these alterations may be early events in carcinogenesis. Quantification of these parameters in Barrett's esophagus might be useful to identify patients at higher risk for progression to cancer.

[Is the successful eradication of Helicobacter pylori sufficient for the healing of peptic ulcer?]. / Elégséges a Helicobacter pylori eradicatiója a peptikus fekély gyógyulásához?

Helicobacter pylori has a major role in the pathogenesis of peptic ulcer disease. Cure of the infection is essential in ulcer healing, but an additional PPI therapy after completing eradication treatment is widespread in clinical practice. In the present work clinical studies evaluating peptic ulcer healing followed or not by PPI treatment after eradication therapy were analyzed. The results of these trials are concordant that only a minority of patients with duodenal ulcer would benefit from prolonged acid suppressive treatment, a successful eradication therapy (that counts for a large proportion) is sufficient. There are less data available concerning gastric ulcer: successful eradication is also essential to ulcer healing and to avoid relapse, however it seems that post-eradication PPI therapy might be beneficial.

[Gaucher's disease: pathogenesis, diagnosis and therapy]. / Gaucher-kór: patogenezis, diagnózis, kezelés.

Gaucher's disease is the most common lysosomal storage disorder. Gene defect leads to deficiency or decreased activity of glucocerebrosidase followed by the accumulation of glucosylceramide. Most frequently hepatosplenomegaly, anemia, skeletal and hematological abnormalities are present. Different types are known based on the clinical findings. Recently used enzyme replacement therapy seems to eliminate bone marrow transplantation and has favourable effects on symptoms and outcome. Development of gene therapy (reintroduction of missing DNA sequence) hints the possibility of real causal therapy of the disease.

[Osteoporosis associated with inflammatory bowel diseases]. / Gyulladásos bélbetegségeket kíséró osteoporosis.

Inflammatory bowel diseases, most frequently Crohn's disease, are frequently accompanied by decreased bone mineral content (30-70%). The osteopenia is not explained by the side effects of treatment or the secondary malabsorption. There must be a common pathological pathway in the background. The mineral content of bones is most easily measured by dual-ray absorptiometry. The measurement should be performed at the time of the diagnosis of bowel disease. It is useful to perform some routine laboratory examinations (serum calcium and phosphate, urinary calcium excretion level, etc.) and some special tests (serum osteocalcin and crosslaps) to exclude some other pathological pathways as well as to plan the anti-osteoporotic therapy. Appropriate calcium and vitamin-D supplementation is essential in prevention and therapy as well. Several drug-classes have proven useful in the therapy of severe osteoporosis associated with inflammatory bowel diseases such as bisphosphonates, hormone replacement therapy, selective estrogen receptor modulators and calcitonin. The authors provide an algorithm for the therapy of metabolic bone disease in inflammatory bowel disease.