Double-balloon endoscopy for small intestinal disease: a single-center experience in Hungary.

BACKGROUND: We report on our experience with the Fujinon EN-450 T5 therapeutic double-balloon endoscope (DBE) and compare our findings with the results of earlier capsule endoscopy. MATERIAL/METHODS: Between August 2005 and July 2009, 150 DBE procedures were conducted in 139 consecutive patients (M/F: 67/72, age: 51.1 years, SD: 18.6 years) who presented at our tertiary referral hospital. The results of previous capsule endoscopy (CE) examinations were available in 27 patients. The indications for DBE included obscure gastrointestinal bleeding (OGIB) in 83 patients, suspected/known IBD in 25, and polyposis/suspected neoplasia in 29 patients. All of the examinations were performed at our outpatient clinic. RESULTS: In OGIB, abnormal small-bowel findings were noted in 50 patients (60.2%) including angiodysplasias, erosions, and small ulcers. Malignancy was found in 6 patients (7.2%), while an intervention was carried out in 24 patients. In suspected IBD cases, IBD was diagnosed in 5/13 cases. In known IBD patients, assessment of the extent as well as disease behavior and activity was the indication. In polyposis/suspected malignancy, polyps were removed by snare polypectomy in 8 Peutz-Jeghers patients, while primary adenocarcinoma was diagnosed in 4. The concordance of CE and DBE findings was 51.8% (14/27), while in 2 cases DBE provided significantly new information, including 1 malignancy. The average insertion length was app. 213 cm (range: 70-480 cm). CONCLUSIONS: Based on our experience, DBE is a safe and useful method for evaluating and treating small-bowel disease in selected patients with obscure bleeding, IBD or polyposis syndromes. The concordance of DBE and CE in this real-life setting was only fair.

The disease burden of colorectal cancer in Hungary.

The aim of the paper is to give an overview of the epidemiology, treatment pattern and quality, as well as policy issues and disease burden of colorectal cancer (CRC) in Hungary. Colorectal cancer is the second most common cause of cancer-related death in both males and females in Hungary. The Hungarian Cancer Registry collects data on the epidemiological characteristics of CRC. Two pilot programmes (1997/1998 and 2003/2004) were conducted for population-based screening of CRC using both immunological and guaiac faecal occult blood testing (FOBT). The National Health Insurance Fund Administration (NHIFA) spends altogether 38.9 million a year on the treatment of CRC. It is hoped that the introduction of an accepted and cost-effective screening programme for CRC can reduce the high CRC burden in Hungary.

Association of beta-defensin 1 single nucleotide polymorphisms with Crohn's disease.

OBJECTIVE: It has been suggested that deficient defensin expression is associated with the chronic inflammation of Crohn's disease. The regional localization of Crohn's disease, ileal or colonic disease can be linked to different defensin profiles. As constitutive beta-defensin 1 has a colonic expression, we considered it of interest to investigate single nucleotide polymorphisms (SNPs) of the beta-defensin 1 gene (DEFB1) in Crohn's disease. MATERIAL AND METHODS: Three SNPs of the DEFB1 gene, DEFB1 G-20A (rs11362), DEFB1 C-44G (rs1800972) and DEFB1 G-52A (rs1799946), were genotyped either by Custom TaqMan SNP genotyping assays or by restriction fragment length polymorphisms (RFLP) in 190 patients with Crohn's disease and 95 Hungarian controls. RESULTS: It was found that the G-20A and C-44G SNPs had a strong association with the colonic and ileocolonic localizations of the disease, respectively, but no association was detected for the ileal localization. A significantly higher frequency of the GA genotype of G-20A was observed among patients with colonic localization (60%) as compared with healthy controls (39%), with an odds ratio (OR) of 2.39. The GG genotype of C-44G SNP, which is regarded as a protective genotype, was much less frequent (4%) among patients than among controls (12%), OR 3.367. CONCLUSIONS: These results indicate that genetic variations in the DEFB1 gene encoding constitutive human beta-defensin 1 may be associated with the risk for Crohn's disease and may determine disease phenotype, e.g. colonic localization.

Double-balloon enteroscopy for the diagnosis and treatment of obscure bleeding, inflammatory bowel diseases and polyposis syndromes: we see more but do we know more?

BACKGROUND/AIMS: Our aim was to report our experience with the Fujinon EN-450 T5 therapeutic double-balloon endoscope (DBE) in the diagnosis of small bowel diseases. METHODOLOGY: Between August 2005 and October 2006, 52 DBE procedures were conducted on 47 consecutive patients (M/F: 22/25, age: 51.6 SD 19.5 years) presenting at our tertiary referral hospital (35 and 7 patients from oral and anal route, respectively; 5 patients from both). All procedures were performed using i.v. anesthesia, at our outpatient clinic. RESULTS: Indication suspected small-bowel bleeding in 28 patients, suspected/known inflammatory bowel syndrome (IBD) in 12 and polyposis/suspected neoplasia in 7. In obscure bleeding small-bowel abnormality was found in 18 patients (64.3%) including angiodysplasias/erosions and one polypoid lesion. In suspected IBD, IBD was diagnosed in 2 out of 8 cases. In patients with polyposis syndromes, polyps were in two Peutz-Jeghers patients, while a further patient with suspected stenosis was diagnosed with primary adenocarcinoma. The average insertion length was app. 213cm. No severe complications were observed. CONCLUSIONS: Based on our experience DBE is a safe and useful method for evaluating and treating small bowel disease in selected patients with obscure bleeding, IBD or polyposis syndromes, however the clinical importance of minute lesions still needs to be determined.

[Crohn's disease of the duodenum. Clinical signs, diagnosis, conservative and surgical treatment]. / A duodenum Crohn-betegsége, klinikai jelek, diagnosztika, gyógyszeres és sebészi kezelés.

UNLABELLED: Duodenal localization of Crohn's disease is rare, accounting for only 0.5-4% of all cases. Most common complaints are gastric outlet obstruction and weight loss. Histologic findings of endoscopic biopsy are frequently not definitive, making differentiation from other, benign structures complicated. There are also no standard guidelines regarding indications for surgical management. PATIENTS AND METHODS: We reviewed the cases of three surgically managed patients with duodenal Crohn's disease at the 1st Department of Surgery, Semmelweis University of Medicine, Budapest, during a 5-year period (2002-2007). All three patients had persistent symptoms of stomach emptying disorder despite medical therapy and had severe weight loss (13-30 kg). In two cases resection of the stenotic duodenum was performed successfully using Billroth II method. Gastro-jejunal bypass was performed in one case, where the descendent duodenum was inflamed. RESULTS: All patients have been asymptomatic since surgery (9-45 months of follow-up) and recovered their earlier bodyweight. The postoperative period was uneventful. CONCLUSIONS: There is indication of surgery in cases of stenosing duodenal Crohn's disease, when medical therapy is not successful, but long-standing malnutrition should be treated preoperatively. We found perioperative morbidity to be similar in patients with duodenal Crohn's and in those with Crohn's disease of other intestinal locations.

Common NOD2/CARD15 variants are not associated with susceptibility or the clinicopathologic characteristics of sporadic colorectal cancer in Hungarian patients.

BACKGROUND: Epidemiological observations suggest that cancer arises from chronically inflamed tissues. Inflammatory bowel disease (IBD) is a typical example as patients with longstanding IBD are at an increased risk for developing colorectal cancer (CRC) and mutations of the NOD2/CARD15 gene increase the risk for Crohn's disease (CD). Recently, NOD2/CARD15 has been associated with a risk for CRC in some studies, which stemmed from ethnically diverse populations. Our aim was to identify common NOD2/CARD15 mutations in Hungarian patients with sporadic CRC. METHODS: A total of 194 sporadic CRC patients (m/f: 108/86, age at diagnosis of CRC: 63.2 +/- 9.1 years old) and 200 healthy subjects were included. DNA was screened for SNP8, SNP12 and SNP13 NOD2/CARD15 mutations by denaturing-HPLC and confirmed by direct sequencing. RESULTS: NOD2/CARD15 mutations were found in 28 patients (14.4%) and in 23 controls (11.5%, p = NS). Allele frequencies for SNP8/R702W (1.8% vs. 1.5%) SNP12/G908R (1.8% vs. 1.8%) and SNP13/3020insC (3.6% vs. 2.5%) were also not statistically different between patients and controls. The clinicopathologic characteristics of CRC patients with or without NOD2/CARD15 mutations were not significantly different. CONCLUSION: Our results suggest that common NOD2/CARD15 mutations alone do not contribute to CRC risk in the Hungarian population.

[Double-balloon endoscopy for the diagnosis and treatment of small intestinal disease: an initial experience from 25 examinations]. / A kettos ballonos endoszkópia szerepe a vékonybél betegségeinek diagnózisában és kezelésében: kezdeti tapasztalataink az elso 25 vizsgálat során.

UNLABELLED: Until recently, only the proximal small bowel was accessible for diagnostic and therapeutic endoscopy. Endoscopic evaluation of this organ has often required open laparotomy with surgically assisted passage of the endoscope through the intestine. Recently, Yamamoto et al have developed a new method, double-balloon endoscopy (DBE) that allows high-resolution visualization and therapeutic interventions in all segments of the GI tract. Our aim was to report our early experience with the Fujinon EN-450 T5 therapeutic double-balloon endoscope. PATIENTS AND METHODS: Between August 2005 and March 2006, 25 DBE was conducted in 23 consecutive patients (M/F: 13/10, age: 51.8 +/- 16.5 years) presenting at our tertiary referral hospitals (17 and 4 patients from the oral or the anal route, respectively; 2 patients from both). All procedures were done by i.v. anesthesia, at our outpatient clinic. After the procedure, the patients were monitored in a recovery room for at least 4h before discharge. RESULTS: The main indication for DBE was suspected small-bowel GI bleeding (11), diagnosis or complications of IBD (7), polyposis syndrome (3), stenosis (1) and insertion of jejunal catheter in one case. Twelve out of 22 patients (54.5%) had a small-bowel finding, with 16 of 22 (72.7%) of the patients having a more accurate diagnostic input. The average insertion length was app. 165 cm (range 50-350 cm, SD 97). Patients' tolerance of the procedure was excellent. No severe complications were recognized. CONCLUSIONS: Based on our limited experience double-balloon enteroscopy is a safe and useful method to evaluate and treating small bowel disease in selected patients, including patients with suspected small-bowel strictures, in whom capsule endoscopy is contraindicated.

Myocardial infarction is associated with Spl binding site polymorphism of collagen type 1A1 gene.

OBJECTIVE: Human atherosclerotic lesions contain collagen type I, which plays a pivotal role in atherosclerotic plaque stability. In contrast, the normal coronary arteries do not express this type of collagen. Data have shown that the collagen type 1A1 (COL1A1) gene Sp1 binding site (-1245 G/T) polymorphism is associated with disturbed collagen protein production. METHODS: In our study, COL1A1 gene Sp1 polymorphism was investigated in 136 patients with myocardial infarction (MI) 5 months after the acute phase, and 212 age-matched control subjects in association with any cardiovascular risk factors (such as serum adiponectin levels, hyperinsulinaemic status, hyperlipaemia). RESULTS: The "SS" genotype of the COL1A1 gene was found to occur significantly more frequently in patients surviving a MI, as compared to the control group and the "Ss" and "ss" genotype frequencies (the presence of the s allele) were lower in our patients, than in control group. However, the occurrence of cardiovascular risk factors was significantly higher among the "s" allelic carriers as compared to patients carrying the "S" allele of the COL1A1 gene. CONCLUSION: Our results raise the possibility that COL1A1 gene Sp1 polymorphism might have an impact on the development of MI.

Location and age at onset of colorectal cancer in Hungarian patients between 1993 and 2004. The high number of advanced cases supports the need for a colorectal cancer screening program in Hungary.

BACKGROUND: In recent decades, the incidence of proximal colorectal cancer (CRC) in North America and Western Europe has steadily increased, while that of the distal tumors has shown a corresponding decrease. Our aim was to investigate the change in age at diagnosis, the gender, location and cancer stage of CRC cases over the last 12 years in a large number of Hungarian patients. PATIENTS AND METHODS: The clinical and histological data of 1694 CRC patients (M/F: 917/777, age at diagnosis: 65.2 +/- SD 12.5 years), diagnosed at the First Department of Medicine and the First Department of Surgery of Semmelweis University, Budapest, Hungary, between January 1, 1993 and December 31, 2004, were analyzed retrospectively. RESULTS: CRCs were rectal or left-sided in 70% and proximal (transverse, ascending or cecum) in 30% of the cases. The proportion of rectal carcinomas increased over the observed period (1993-1998: 31.6% vs. 1999-2004: 42.1%, p=0.001), while the proportion of proximal tumors remained stable. Eleven percent of CRCs were diagnosed under the age of 50 years. The age at diagnosis did not differ between males and females, but was lower in patients with rectal tumors compared to other localizations (p=0.02); 75.7% of the CRCs were T3-T4 at diagnosis and lymph node metastases could be detected in 47.7%. CONCLUSION: In contrast to Western European and North American trends, the proportion of proximal CRCs did not increase in Hungary over the observed period. Almost two-thirds of all cancers were left-sided. The high percentage of locally advanced tumors and lymph node metastases supports the need for colorectal screening programs.

[Change in location of colorectal cancer in Hungarian patients between 1993-2004]. / A colorectalis rákok lokalizációjának változása Magyarországon 1993 és 2004 között.

UNLABELLED: The incidence of proximal tumours in Western countries has steadily increased while that of distal tumours has shown a corresponding decrease. Our aim was to investigate the prevalence, location and histology of colorectal cancers in the last twelve years in Hungarian patients. PATIENTS AND METHODS: Clinical data of 1738 patients diagnosed with colorectal tumors (M/F: 940/798, mean age at diagnosis: 65.2 +/- 12.5 years) between 1st of January 1993 and 31st of December 2004 at the 1st Internal Medicine and 1st Surgery Department of Semmelweis University were enrolled. Pathology and clinical data were analysed retrospectively. The observed periods were the following 1993-1998 and 1999-2004. RESULTS: 1694 (97.5%) of the patients had adenocarcinoma (CRC), 15 anaplastic cancers, 9 carcinoid, 6 planocellular, 5 GIST, 3 leiomyoma and 2-2 melanoma, lymphoma and shigillocellular cancers were diagnosed. 75.7% (943/1246) of the CRCs were diagnosed at locally advanced stage (T3-T4), and 47.7% (521/1093) of CRC patients had lymph node metastasis at the time of diagnosis. 11.0% of the CRCs were diagnosed in <50 year-olds (<40 years: 2.5%, <30 years: 0.5%). The location of the CRC was distal in 1186 (rectum: 53.9%, sigmoid/descending: 46.1) and proximal in 508 cases. Synchronous cancers were detected in 12 patients (age: 68.8 +/- 11.6 years, gender: 11 male/1 female, location: rectum and transverse in 6, rectum and ascending/caecum in 5 patients). Age at diagnosis was not different according to gender (M/F: 64.8 +/- 12.0 years vs. 65.8 +/- 12.9 years), but it was lower in patients with rectal cancer compared to left or right sided cancers (64.1 years vs. left: 66.1 years, right: 66.0 years, p = 0.02). Rectal CRC was more common in males, while the proportion of proximal cancers was lower (rectum, M/F: 41.2% vs. 33.5%, proximal M/F: 26.8% vs. 33.8%, p = 0.003). The proportion of rectal cancers increased over the observed period (1993-1998: rectal: 31.6% vs. 1999-2004: 42.1%, p = 0.002). CONCLUSIONS: In contrast to Western countries, the proportion of proximal CRC did not become higher in Hungary. Still more than two-third of the patients were diagnosed to have distal cancers. The proportion of male patients was higher in this subset of CRC. The high percentage of locally advanced and metastatic cancers supports the need for colorectal screening program in Hungary.

[Incidence and pathologic distribution of esophageal cancers at the gastro-esophageal junction between 1993-2003]. / A nyelocso és a gastrooesophagealis junctio daganatainak gyakorisága és szövettani megoszlása 1993-2003 között.

UNLABELLED: There was a significant change in the histology of oesophageal cancers in the last few decades. The incidence of oesophageal adenocarcinoma has risen considerably, now it is equally or even more prevalent than squamous cell cancers in some North American and Western European countries. As no Hungarian data is available, the authors' aim was to investigate the prevalence and histology of oesophageal and gastrooesophageal junction cancers in the last decade. PATIENTS AND METHODS: 451 patients diagnosed with oesophageal (n = 371, 296 male/75 female, mean age at diagnosis: 57.9 SD 10.1 years) or cardia (n = 80, 58 male/22 female, mean age at diagnosis: 65.2 SD 13.4 years) cancer between 1st of January 1993 and 31st of December 2003 at the 1st Internal Medicine and 1st Surgery Department of Semmelweis University were enrolled. Pathology and clinical data were analysed retrospectively. RESULTS: 93% (n = 345) of the patients with oesophageal cancer had squamous cell carcinomas, while adenocarcinoma was only diagnosed in 15 (4%) patients. Mean age at diagnosis was lower in patients with squamous cell cancer (57.4 SD 10.0 years) compared to patients with adenocarcinoma (66.9 SD 8.8 years, p = 0.001). Male-to-female ratio was 4:1 in patients with squamous cell carcinoma (277/68) and undifferentiated carcinoma (9/2), while it was 2:1 in patients with adenocarcinoma (10/5). According to the location 1.3% of cancers of the midthoracic oesophagus and 8.6% of the lower oesophagus were adenocarcinoma. The proportion of adenocarcinoma remained stable over the observed period (1993-1997: 3.7% vs. 1998-2003: 4.3%). In contrast, 71.25% (57/80) of the gastrooesophageal junction cancers and overall 15.9% (72/451) of the cancers of the oesophagus and gastrooesophageal junction were adenocarcinoma (1993-1997: 17.2% vs. 1998-2003: 14.7%). CONCLUSIONS: Since only a few percentages of authors patients with oesophageal cancers were diagnosed to have adenocarcinoma and its proportion remained stable over the observed period, it seems that in contrast to North American and Western European countries, adenocarcinoma is still infrequent in Hungary.

Mucocele of the appendix: an unusual cause of lower abdominal pain in a patient with ulcerative colitis. A case report and review of literature.

The authors report the case of a 60-year-old male patient. In November 2001 he developed intestinal symptoms of bloody diarrhea and abdominal pain. Colononoscopy and biopsy established the diagnosis of ulcerative colitis (proctosigmoiditis). The disease activity was moderate at the beginning. No significant laboratory alterations were found (including CEA, CA19-9), and mesalazine was started orally. He was in remission until November 2003, when he was admitted to our Outpatient Clinic for upper and right lower abdominal pain and bloody diarrhea. Colonoscopy found proctosigmoiditis with a moderate activity, gastroscopy revealed chronic gastritis, laboratory data was normal. Treatment was amended with mesalazine clysma and methylprednisolone (16 mg) orally. Symptoms ameliorated; however, right lower abdominal pain persisted. US and CT examination demonstrated a pericecal cystic mass (11 cm x 3.5 cm). At first pericecal abscess was suspected, as the previous US examination (6 mo earlier) had revealed normal findings. Fine needle aspiration was performed. Cytology confirmed the diagnosis of mucocele. The patient underwent partial cecum resection and extirpation of the mucocele. He recovered well and the final histology revealed a cystadenoma of the appendix. Follow up was started. The patient is now free of symptoms. Although primary adenocarcinoma of the appendix is uncommon, the authors emphasize that preoperative diagnosis of an underlying malignancy in a mucocele is important for patient management; however, it is difficult on imaging studies.

[Significance of serum calcium levels in colorectal cancer]. / A szérumkalciumszint jelentosége colorectalis daganatos betegekben.

INTRODUCTION: Based on the available studies, a link can be established between colorectal cancer (CRC) and low intake of calcium and vitamin D. According to the most recent results, the serum calcium level is mainly determined by genetic factors. One of the key elements of this is calcium-sensing receptor. AIM: The authors of this article examined patients in which CRC had recently been discovered. Particular attention was devoted to the relationship between the calcium metabolism of the patients, and the levels of AFP, CEA, CA 19-9 (which can be considered as prognostic factors). PATIENTS AND METHODS: The authors examined a total of 70 patients. Furthermore they examined the calcium-sensing receptor (CaSR) A986S polymorphism, as well as the different CaSR genotypes and the relationship with the data stated above. RESULTS: A lower level of ionized calcium was found in the CRC patients with normal 25 (OH) vitamin D levels. Beyond this, the ionized calcium level was inversely correlated with the level of CA 19-9 tumor markers. There were no differences in the CaSR genotype, between the CRC patients and the general population, beyond this, the genotypes did not correlate with other data being examined. CONCLUSION: With these results, the authors of this article have concluded that a lower level of calcium can be a pathogenic and prognostic factor in colorectal cancer.

Relationship between serum calcium and CA 19-9 levels in colorectal cancer.

AIM: To examine the calcium metabolism of colorectal cancer (CRC) in patients with colorectal cancer and control patients. METHODS: Seventy newly diagnosed CRC patients were included. The healthy control group was age and gender matched (n=32). Particular attention was devoted to the relationship between serum calcium of patients, and levels of AFP, CEA, carbohydrate antigen 19-9 (CA 19-9) (that could be considered as prognostic factors). Furthermore, the Ca-sensing receptor (CaSR) gene A986S polymorphism was investigated in these patients, as well as the relationship between different CaSR genotypes and the data stated above. RESULTS: A lower level of ionized calcium (also corrected for albumin) was found in the serum of CRC patients with normal 25(OH) vitamin D levels. The ionized calcium concentration was inversely correlated with the serum level of CA 19-9. There was no difference in the distribution of CaSR genotypes, between CRC patients and general population. The genotypes did not correlate with other data examined. CONCLUSION: Based on these results, lower levels of serum calcium might be a pathogenic and prognostic factor in colorectal cancer.

[Familial adenomatous polyposis coli--case report]. / A familiaris adenomatosus polyposisról egy eset kapcsán.

The authors report the case of a young 35 year-old male patient, investigated due to thrombocytosis for three years. First the diagnosis of chronic myeloproliferative disease was made. The diagnosis of familial adenomatous polyposis was only evident in advanced stage of the disease. Upper abdominal US, abdominal CT, double-contrast barium enema examination and colonoscopy proved advanced synchronous colorectal cancers (sigmoid and descending colon) with liver metastases along with polyposis throughout the whole large bowel. Days after the diagnosis was made the patients condition deteriorated rapidly and he died with septic symptoms suggesting bowel perforation and pneumonia. Beside the case report the authors try to give a short overview of the current literature of relatively rare but potentially fatal hereditary colon cancer syndromes to awake the attention of the clinicians to investigate more cautiously the background of unexplained clinical-laboratory signs in young adults.