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Volume 71 - 2008 - Fasc.2 - Original articles

EGFR-immunohistochemistry in colorectal cancer and non-small cell lung cancer : Comparison of 3 commercially available EGFR-antibodies

Background : Epidermal Growth Factor Receptor (EGFR)- targeted therapies are currently used for the treatment of metasta- sized colorectal cancer (CRC) and non small cell lung cancer (NSCLC). Patient selection for this treatment is based on immuno- histochemical (IHC) testing for EGFR. The rising amount of commercially available EGFR-antibodies makes standardisation of EGFR-IHC necessary. The goal of this study was to analyse possible discrepancies between 3 antibodies against EGFR. Patients and methods : 36 formalin-fixed samples of CRC (n = 26) and NSCLC (n = 10) were stained with 3 antibody-clones : 2- 18C9 (DakoTM); 31G7 (VentanaTM) and 111.6 (Labvision NeomarkersTM). Interpretation of stains includes assessment of % positive cells, evaluation of cut off values and staining intensity. Results : With a 1% cut-off, the 2-18C9 clone stained 86% of the cases positive, the 31G7-clone 77% and the 111.6-clone 52%. With a 10% cut-off, percentages declined to 77%, 61% and 30% respectively. The 2-18C9-clone showed the highest staining intensity. The 2-18C9 clone and the 31G7-clone showed a concor- dance rate of 90%. Conclusions : IHC staining with 3 different antibody clones directed against EGFR shows indeed differences in staining results : the percentage of positive cells and staining intensity are variable. A correct cut-off value for a positive result is important and can be different depending upon the antibody. Appropriate validation of an antibody is essential before it can be used for selection of patients. (Acta gastroenterol. belg., 2008, 71, 213-218).

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EUS-FNA and FDG-PET are complementary procedures in the diagnosis of enlarged mediastinal lymph nodes

Background and Study aims : Transoesophageal endosonography with fine needle aspiration (EUS-FNA) and 2-deoxy-2-[fluorine- 18]fluoro-D-glucose positron emission tomography (FDG-PET) are now standard diagnostic procedures of the mediastinum. Our aim was to compare their value in the assessment of enlarged mediasti- nal lymph nodes detected by computed tomography. Patients and methods : Forty consecutive patients with a suspi- cion of cancer or a history of pulmonary, digestive, urogenital or mammary neoplasia and presenting with supracentimetric lymph nodes on computed tomography underwent whole body FDG-PET and EUS-FNA. Final diagnosis of malignancy was obtained by cytology, surgery or long-term follow-up. Results : EUS-FNA showed a sensitivity, specificity and accura- cy for detection of malignancy of 79.3, 100 and 85%, respectively. The biopsy material was adequate for cytological examination in 37 patients. Sensitivity, specificity and accuracy of PET were 100, 54.5 and 87.5%, respectively. FDG-PET correctly diagnosed the primary site in 27 patients, and showed additional unknown extrathoracic metastatic sites in 15 patients. The five false positive results observed with FDG-PET consisted in a final diagnosis of sarcoidosis, tuberculosis, anthracosilicosis and reactive lymph nodes, respectively. The association of FDG-PET and EUS-FNA avoided more invasive procedures (mediastinoscopies or staging surgery) in 34 patients. Conclusions : EUS-FNA and FDG-PET are complementary diagnostic procedures combining the high sensitivity of FDG-PET and the high specificity of EUS-FNA to accurately diagnose malig- nancy in enlarged mediastinal lymph nodes identified by CTscan. The combination of the two procedures in selected cases with pul- monary cancer or extra-thoracic tumours avoided more invasive diagnostic and surgical procedures. (Acta gastroenterol. belg., 2008, 71, 219-229).

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An economic evaluation of vasoactive agents used to treat acute bleeding oesophageal varices in Belgium

Background and study aims : Increasingly, cost influences all areas of healthcare, including the management of life threatening events, such as bleeding oesophageal varices (BOV). In light of the need to control costs, an economic evaluation of vasoactive agents used to treat cirrhotic patients with BOV within the emergency set- ting in Belgium has been assessed. Patients and methods : A previously reported economic evalua- tion of vasoactive agents used to treat BOV was identified and adapted to the Belgium hospital setting. The economic evaluation was based on double-blind randomised controlled trials of vasoac- tive agents previously reported as Cochrane meta-analyses. Belgian cost data was obtained from local published sources and hospital databases. We assessed average disaggregated and aggre- gated treatment costs, average and incremental cost per quality adjusted life years (QALYs) and life-years gained (LYG). Results: Total treatment costs at 1 year were: terlipressin € 2,734 ; somatostatine € 2,972 ; octreotide € 2,801 ; and placebo € 2,874. The average costs per QALY were : terlipressin € 4,672 ; somatostatine € 5,878 ; octreotide € 5,540 ; and placebo € 5,687. In the cost per LYG analysis terlipressin achieved the lowest cost per life-year. Results from the incremental cost per QALY and LYG analysis indicated that terlipressin was the most cost-effective agent. Conclusions : One year simulations indicate somatostatine is the most expensive treatment option and terlipressin the least costly. Amongst the vasoactive products, the incremental analysis indicat- ed terlipressin was dominant when compared with octreotide and somatostatine because of improved survival and cost-saving poten- tial that is likely attributed to avoiding additional and more costly interventions. (Acta gastroenterol. belg., 2008, 71, 230-236).

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Porphyria cutanea tarda and liver disease A retrospective analysis of 17 cases from a single centre and review of the literature

Background/aims : Sporadic Porphyria Cutanea Tarda (sPCT) is associated with liver disease, e.g. HCV infection, haemochromato- sis and especially alcoholic liver disease. We conducted a retro- spective analysis on the prevalence of liver disorders in association with Porphyria Cutanea Tarda (PCT), in a university referral centre. Methods : The PCT cases were retrieved from computerized databases. Patient files lacking information on the presence of con- comitant liver disease were excluded from further analysis. Results : 29 PCT patients were retrieved from our databases, of which 17 patients with sPCT were retained for further analysis. Patients were middle aged (mean age : 43 ± 3) and there was no gender difference (10 males vs. 7 females). Almost all patients had iron overload (14/17). 5 patients had chronic HCV, with type 1b in 3 of them, 7 abused alcohol, 4 patients had hereditary haemochro- matosis (3 homozygous C282Y - 1 heterozygous H63D/C282Y). In 3 patients sPCT was associated with medication intake and one patient had chronic hepatitis B (HBV). 13 patients were treated with phlebotomies, with success in 11/13. 4 patients were treated with chloroquine, 3 of which also underwent phlebotomies. Of the 5 patients with HCV, 3 were successfully treated with combined antiviral therapy ; one of them is planned to be treated ; one patient never received therapy and was lost from follow-up. One patient developed hepatocellular carcinoma (HCC) during a medi- an follow-up of 24 years. Conclusions : We found a significant association between sPCT and liver disorders, such as chronic HCV infection, alcohol abuse, iron overload and hereditary haemochromatosis. Therefore, patients presenting with PCT should be screened for concomitant liver disease. Iron overload is present in a majority of patients, the majority of patients can be successfully treated with phlebotomies. The risk of developing HCC in our sPCT patients and in literature is low. (Acta gastroenterol. belg., 2008, 71, 237-242).

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One-step chromoendoscopy and structure enhancement using balsamic vinegar for screening of Barrett's esophagus

Background and study aims : Screening for specialized columnar epithelium (SCE) within columnar lined esophagus (CLE) with standard video endoscopes is not reliable enough. Several methods to improve accuracy of predicting presence of SCE like chromoen- doscopy with vital stains or structure enhancement with acetic acid have been introduced but data up to now remains controversial. The present prospective study was conducted to evaluate a combi- nation of chromoendoscopy and acetic acid structure enhancement using the naturally brownish coloured balsamic vinegar during routine upper endoscopy. Patients and methods : Between March and July 2006 20 patients with macroscopic suspicion for SCE during routine endoscopy were included prospectively. Saline diluted balsamic vinegar (3%) was administered with a spraying catheter at the distal esophagus. After 1 minute the distal esophagus was evaluated for the presence of SCE according to the mucosal surface pattern (pattern I-II : round pits/circular pattern predicting gastric epithelium ; pattern III-IV : ridged/villous pattern predicting Barrett's epithelium). Only HR-videoendoscopes without magnification were used. After presence or absence of SCE was defined by the endoscopist target- ed biopsies of the CLE were performed. Histological results were compared with endoscopic findings. Results : In 9 of 20 patients (13 male, 7 female ; mean age 60.0 ± 12.8 years) biopsy specimen revealed SCE within CLE on histology. Prediction of BM after balsamic vinegar staining was possible in all cases. Surface pattern I-II was found in 9 patients and pattern III- IV in 11 patients. Accuracy, sensitivity and specificity for BV stain- ing predicting SCE were 90%, 100% and 82%, respectively. Conclusion : Chromoendoscopy with balsamic vinegar combines the advantages of chromoendoscopy and structure enhancement by acetic acid for detection of SCE. The reliability in predicting the presence of SCE was high in this prospective feasibility study. (Acta gastroenterol. belg., 2008, 71, 243-245).

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Addition of somatostatin-14 to a standard Total Parenteral Nutrition-mixture in the treatment of fistulae : a clinical, double-blind, randomised, cross-over study

Background / study aims : Somatostatin and total parenteral nutrition (TPN) are routinely used in the treatment of pancreatic and enterocutaneous fistulae. The objective of this clinical ran- domised cross-over study was to investigate the serum levels of somatostatin infused alongside TPN by a separate intravenous line, and when it had been added to the TPN mixture. Patients / methods : The subjects were recruited by the treating physicians and the nutrition nurses. From the patients who started the study, no one dropped out. Ten patients were treated with a standard TPN mixture and somatostatin 6 mg/day. Patients were randomised to two possible regimens : 'somatostatin plus TPN - somatostatin separately - somatostatin plus TPN' or 'somatostatin separately - somatostatin plus TPN - somatostatin separately'. Each regimen consisted of 3 ?? 3 days of therapy, during which, serum levels of somatostatin were measured daily. Pre- and post- treatment samples were also analysed. Results : When somatostatin was infused separately, the mean serum level was 884.8 pg/ml (SD : 557.3 ; range : 54-1900). When added to TPN, the mean serum level was 807.5 pg/ml (SD: 505.8 ; range 162-2279) (p value of difference = 0,473). The mean pre- treatment level was 17.1 pg/ml (SD : 7.5 ; range : 8-33), and post- treatment was 32.8 pg/ml (SD : 26.5 ; range : 16-97). Conclusions : These results demonstrate that serum levels of somatostatin are similar in both treatment regimens and therefore may be added to a TPN mixture. Sponsorship : This study was performed with an unconditional Educational Grant from UCB-Belgium. The authors did not have any conflict of interest in UCB-Belgium. (Acta gastroenterol. belg., 2008, 71, 246-249).

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Primary aorto enteric fistula : report of 18 Belgian cases and literature review

Background and study aims : We searched for Belgian cases of primary aorto enteric fistula (PAEF). After reviewing the literature we compared our data concerning incidence, types, pathogenesis, aetiology, clinical presentation, diagnostic modalities, treatment and prognosis of PAEF. We especially focus on the clinical picture and diagnostic options. Patients and methods : We present our atypical case report. A questionnaire was send to 196 Belgian vascular surgeons in order to evaluate retrospectively the Belgian experience with PAEF. A Medline search of relevant literature from January 1980 to February 2006 was conducted. Results: In total 18 Belgian cases of PAEF were detected usually originating from infrarenal abdominal aorta (83%), ending in the third or fourth part of the duodenum (67%) and affecting men (94%) with a mean age of 70 years old. Main cause is aneurysm (89%). Gastrointestinal bleeding is the main symptom (83%). Untreated, no one survives and overall mortality is 29%. Most patients are treated with in situ grafts (83%). With our expe- rience we propose a diagnostic flow chart to obtain early diagnosis of PAEF. Conclusions : PAEF is suspected when a patient presents with (considerable) (upper) gastrointestinal blood loss and has a known aneurysm, initial herald bleed or pulsating abdominal mass. In case of hemodynamic instability, prompt surgical exploration is mandatory. Hemodynamically stable patients must undergo con- trast enhanced multislice computerized tomography rather than gastroduodenoscopy or arteriography to make early diagnosis. Surgery is the only definitive life saving treatment. Overall mortal- ity is at least 30%. Late diagnosis, positive peroperative cultures and shock are indicators of poor prognosis. (Acta gastroenterol. belg., 2008, 71, 250-258).

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