[Screening gastroscopy in Germany - first results of the pilot phase of the Prä-GIT study]. / Vorsorgegastroskopie in Deutschland ­ erste Ergebnisse der Pilotphase der Prä-GIT-Studie.

The primary aim of the Prä-GIT study is to collect information on the prevalence and course of precancerous and early malignant lesions in the upper GIT (uGIT) as well as risk factors associated with these lesions in asymptomatic individuals. Study participants presenting for a screening colonoscopy will undergo an additional endoscopic examination of the uGIT in the same session. 5000 participants in 30 endoscopy clinics in Bayern will be included. The pilot study presented here was performed to test the main study protocol as well as the acceptance of an additional uGIT endoscopic examination. METHODS: Three endoscopy clinics in Bayern took part in the three-month pilot study between October and December 2018. Patients presenting for a screening colonoscopy in these clinics were offered an additional endoscopic examination of the uGIT which was performed according to a standard operating procedure (SOP). Furthermore, data on dietary habits and lifestyle, as well as biological samples, were collected. RESULTS: 52 participants were included in three clinics in Altötting, Augsburg and Regensburg. The average age was 63.4 years. The average time spent per uGIT endoscopy was 11 minutes. No complications occurred. One participant showed a polyp of the recessus piriformis. Refluxesophagitis was seen in 21 participants, four participants had Barrett's esophagus with histological evidence of low-grade dysplasia in one patient, and an esophageal polyp with low-grade dysplasia was seen in one participant. Helicobacter-pylori gastritis was documented in 12 participants. Corpus-dominant atrophy was described in one participant, while a duodenal adenoma with low-grade dysplasia was seen in two participants. 100 % and 89 % of study participants gave a blood or a stool sample, respectively. All participants answered the questionnaire on dietary and lifestyle habits. CONCLUSION: The Prä-GIT study was designed to generate a database for premalignant and early cancerous lesions of the uGIT in Germany in asymptomatic individuals presenting for a regular screening colonoscopy. The current pilot study has delivered important insights into the feasibility of the main study protocol. Additionally, the pilot study has shown a high rate of acceptance of an additional uGIT examination in this study population.

Anthocyanins Prevent Colorectal Cancer Development in a Mouse Model.

BACKGROUND: Colorectal cancer is the main leading cause of cancer-related deaths worldwide. Present data suggest that plant-derived anthocyanins have anti-inflammatory and chemopreventive properties. This study was aimed at evaluating the effect of an anthocyanin-rich extract from bilberries on colorectal tumour development and growth in the administration of azoxymethan (AOM)/dextran sodium sulfate (DSS) mouse model. METHODS: Colonic carcinogenesis was induced by AOM and DSS 3 or 5%, respectively, in 50 female Balb/c mice. Mice received either normal food (controls) or a diet containing either 10 or 1% anthocyanin-rich bilberry extract. Colonoscopy took place at week 4 and 9 after initiation of carcinogenesis. After termination at week 9, colon samples were analysed macroscopically and microscopically. RESULTS: Mice receiving 10% anthocyanins showed significantly (p < 0.004) less reduced colon length (12.1 cm [8.5-14.4 cm]) as compared to controls (11.2 cm [9.8-12.3]) indicating less inflammation. Mice fed with 10% anthocyanin-rich extract revealed significantly less mean tumour numbers (n = 1.2) compared to control (n = 14) and anthocyanin 1% treated mice (n = 10.6, p < 0.001). CONCLUSION: Anthocyanins prevented the formation and growth of colorectal cancer in AOM/DSS-treated Balb/c mice. Further studies should investigate the mechanisms of how anthocyanins influence the development of colorectal cancer.

Irinotecan Plus Gemcitabine and Fluorouracil in Advanced Biliary Tract Cancer: A Retrospective Study.

BACKGROUND: Since 2010, combination therapy with gemcitabine and cisplatin is the standard treatment for patients with biliary tract cancer (BTC) based on the ABC-02 trial. However, treatment after first-line progression is less clearly defined. We therefore retrospectively analyzed the efficacy of a 3-drug chemotherapy regimen in patients with advanced BTC. METHODS: Patients with advanced BTC treated with palliative chemotherapy between April 2000 and October 2005 at Regensburg University Hospital were reviewed retrospectively. We analyzed the efficacy and safety of an institutional standard 3-drug regimen consisting of irinotecan, gemcitabine and 5-FU (IGF). One cycle, lasting 21 days, included applications on days 1 and 8 consisting of 75 mg/m2 irinotecan i.v. for 90 min, 1,000 mg/m2 gemcitabine i.v. for 30 min and 2,000 mg/m2 fluorouracil (5-FU) for 24 h. RESULTS: A total of 12 histologically confirmed cases with gallbladder cancer and intrahepatic BTC were reviewed. Fifty percent of the patients (6/12) had been pretreated with other chemotherapies. Median progression-free survival was 9.4 months (1.5-21.5) and median overall survival was 17.2 months (2.5-24.3). Only neutropenia (8%) was observed as an NCI-CTC grade 3 toxicity. Anemia and leucopenia grades 1 and 2 were the most common side effects. CONCLUSIONS: The combination of IGF shows a promising survival benefit with manageable toxicity in patients with advanced BTC. Therefore, this regimen seems to be a feasible second-line treatment option for patients with rapid progression under first-line therapy with gemcitabine and cisplatin and with a good performance status.

Gastrointestinal endoscopy in patients aged 75 years and older: risks, complications, and findings--a retrospective study.

PURPOSE: Endoscopy of the gastrointestinal tract offers simultaneously diagnostic and therapeutic options and is increasingly performed in elderly patients due to a continuously growth of this population segment. Whereas safety data of diagnostic and interventional endoscopy in patients younger than 65 years are well characterized, only scarce data exist for elderly patients older than 75 years. METHODS: We analyzed outcomes and complications of endoscopic procedures with focus on colonoscopy in patients aged 75 and older at a single tertiary referral center in Germany between 1996 and 2006. RESULTS: A total of 3770 endoscopies (2270 gastroscopies, 735 colonoscopies, 765 ERCP) were performed in 1841 patients with a mean age of 79 years (range 75 to 97 years). Seventy-four percent of all patients suffered from relevant comorbidities. Therapeutic interventions were carried out in 43 % of colonoscopies. Complications were observed in approximately 1 %. CONCLUSION: The observed complication rate in diagnostic and therapeutic endoscopic procedures is not increased in elderly patients compared to the reported complication rates in younger patients.

Chronic psychosocial stress increases the risk for inflammation-related colon carcinogenesis in male mice.

Patients with inflammatory bowel diseases (IBDs) have a higher risk of developing colorectal cancer (CRC) than the general population. Furthermore, chronic psychosocial stress increases the likelihood of developing IBD and multiple types of malignant neoplasms, including CRC. Here, for the first time, we investigate the effects of chronic psychosocial stress in male mice on an artificially induced CRC, by employing the chronic subordinate colony (CSC) housing paradigm in combination with the reliable azoxymethane (AOM)/dextran sodium sulfate (DSS) CRC model. Colonoscopy revealed that CSC mice showed accelerated macroscopic suspect lesions. In addition, more CSC mice developed low-grade dysplasia (LGD) and/or high-grade dysplasia (HGD) in the colonic tissue compared to the single-housed control mice (SHC). CSC mice showed an increased number of Ki67+ and a decreased number of terminal deoxynucleotidyl transferase dUTP nick end labeling epithelial cells in colonic tissue. Colonic liver receptor homolog-1 (LRH-1), cyclooxygenase II (COXII), tumor necrosis factor, forkhead box P3 (FoxP3) mRNA as well as colonic ß-catenin, COXII, and LRH-1 protein expression were also increased in CSC compared with SHC mice. Although the number of CD4+ Th cells was increased, a tendency toward a decreased colonic interferon-γ (IFN-γ) mRNA expression was observed. Furthermore, despite an increased percentage of CD3+ cells and CD3+/FoxP3+ double-positive cells within mesenteric lymph node cells of CSC mice, IFN-γ secretion from these cells was unaffected. Altogether, our results suggest that chronic psychosocial stress increases the risk for AOM/DSS-induced and, thus, inflammation-related CRC. Finally, assessment of additional time points may test whether the shift from tumor-protective Th1 cell to regulatory T-cell immunity represents a consequence of increased carcinogenesis or a causal factor involved in its development.

Colonic bowel wall thickening: is there a need for endoscopic evaluation?

PURPOSE: Clinical relevance of colonic bowel wall thickening seen on abdominal CT scans is unknown. Recommendations for further diagnostic procedures are lacking. The aim of this retrospective study was to evaluate detecting of bowel wall thickening on CT scan and findings that were seen in case of endoscopical evaluation. METHODS: The radiological database was retrospectively reviewed for all reports of CT scans from 2003 to 2009 at the University Hospital Regensburg, Germany. Patients with underlying diseases for suspected bowel wall thickening were excluded. RESULTS: Sixty-two patients with bowel wall thickening were detected. Twenty-one percent (13/62) had generalized bowel wall thickening. In 58%, bowel wall thickening was limited to one segment of the colon (36/62), mostly left sided (25/62). Forty-four percent of patients (27/62) were sent to endoscopy. In 15% (4/27), malignancy was suspected, and it could be histologically confirmed in two patients. Nineteen percent (5/27) had normal endoscopy, and 67% (18/62) showed benign findings. CONCLUSION: Colonic bowel wall thickening is not a common finding on CT scan in this study. Consequential endoscopic evaluation was performed in less than 50% of patients. Pathological findings were detected in 80% of these patients. We recommend endoscopical evaluation if bowel wall thickening is reported on CT scan.

Biomarker analysis of cetuximab plus oxaliplatin/leucovorin/5-fluorouracil in first-line metastatic gastric and oesophago-gastric junction cancer: results from a phase II trial of the Arbeitsgemeinschaft Internistische Onkologie (AIO).

BACKGROUND: The activity of the epidermal growth factor receptor (EGFR)-directed monoclonal antibody cetuximab combined with oxaliplatin/leucovorin/5-fluorouracil (FUFOX) was assessed in first-line metastatic gastric and oesophago-gastric junction (OGJ) cancer in a prospective phase II study showing a promising objective tumour response rate of 65% and a low mutation frequency of KRAS (3%). The aim of the correlative tumour tissue studies was to investigate the relationship between EGFR gene copy numbers, activation of the EGFR pathway, expression and mutation of E-cadherin, V600E BRAF mutation and clinical outcome of patients with gastric and OGJ cancer treated with cetuximab combined with FUFOX. METHODS: Patients included in this correlative study (n = 39) were a subset of patients from the clinical phase II study. The association between EGFR gene copy number, activation of the EGFR pathway, abundance and mutation of E-cadherin which plays an important role in these disorders, BRAF mutation and clinical outcome of patients was studied. EGFR gene copy number was assessed by FISH. Expression of the phosphorylated forms of EGFR and its downstream effectors Akt and MAPK, in addition to E-cadherin was analysed by immunohistochemistry. The frequency of mutant V600E BRAF was evaluated by allele-specific PCR and the mutation profile of the E-cadherin gene CDH1 was examined by DHPLC followed by direct sequence analysis. Correlations with overall survival (OS), time to progression (TTP) and overall response rate (ORR) were assessed. RESULTS: Our study showed a significant association between increased EGFR gene copy number (≥ 4.0) and OS in gastric and OGJ cancer, indicating the possibility that patients may be selected for treatment on a genetic basis. Furthermore, a significant correlation was shown between activated EGFR and shorter TTP and ORR, but not between activated EGFR and OS. No V600E BRAF mutations were identified. On the other hand, an interesting trend between high E-cadherin expression levels and better OS was observed and two CDH1 exon 9 missense mutations (A408V and D402H) were detected. CONCLUSION: Our finding that increased EGFR gene copy numbers, activated EGFR and the E-cadherin status are potentially interesting biomarkers needs to be confirmed in larger randomized clinical trials. TRIAL REGISTRATION: Multicentre clinical study with the European Clinical Trials Database number 2004-004024-12.

Fibrin glue in the endoscopic treatment of fistulae and anastomotic leakages of the gastrointestinal tract.

BACKGROUND: Fistulae or leakages of anastomotic junctions of the gastrointestinal tract used to be an indication for surgery. However, patients often are severely ill and endoscopic therapeutic options have been suggested to avoid surgical intervention. PURPOSE: This is a retrospective analysis of fibrin glue application in the treatment of gastrointestinal fistulae or anastomotic leakages. AIM: The aim of this study was to investigate the value of fibrin glue in the treatment of gastrointestinal fistulae and leakages. METHODS: From September 1996 to November 2002, 52 patients with gastrointestinal fistulae or insufficiencies have been treated endoscopically including the use of fibrin glue (Tissucol Duo S®, Baxter, Unterschleissheim, Germany). Clinical data comprising concomitant therapies and results were analysed by chart review. RESULTS: Twenty-six lesions were located in the oesophagus or gastroesophageal junction, 4 in the stomach, 7 in the small intestine, 13 colorectal and 2 in the pancreas. The duration of treatment ranged from 12 to 1,765 days. Two to 81 ml fibrin glue (median 8.5) was used in 1-40 sessions (median 4). All patients received antibiotics; additional endoscopic options were frequently applied. Endoscopic therapy cured 55.7% patients (n = 29); 36.5% (n = 19) were cured with fibrin glue as sole endoscopic option. In 23.1% (n = 12), surgical intervention became necessary. Patients without major infectious complications tended to have a higher cure rate without surgery (87.5% vs. 50%). Eleven patients died (21.1%). CONCLUSION: Endoscopic therapy is a valuable option in the treatment of fistulae and anastomotic insufficiencies of the gastrointestinal tract. It usually is applied repeatedly. Fibrin glue is a mainstay of this procedure. Major infectious complications seem to define a subgroup of patients with poorer outcome.

Causes of bolus impaction in the esophagus.

BACKGROUND: Bolus impaction in the esophagus is a common indication for emergency endoscopy. The aim of this study was to determine the most common causes of esophageal bolus impaction. METHODS: In this retrospective study, data of 54 patients (41 male, 13 female) with bolus impaction in the esophagus were analyzed. Type and localization of the bolus and the endoscopic extraction tool used were evaluated. In 48 of 54 patients (89%), biopsy samples were taken of the esophagus for histological examination. RESULTS: Mean age of the patients was 53 ± 20 years. Fourteen of 54 patients (26%) had experienced bolus impaction previously. Meat bolus (n = 35, 65%) was the most common cause of esophageal obstruction. In most cases, boluses were found in either the distal (n = 31) or the proximal (n = 18) esophagus. In 22 patients (41%), the bolus was pushed into the stomach by the endoscope. In most other cases the bolus, including foreign bodies, could be removed with the 5-arm polyp grasper or alligator forceps. Main causes of bolus impaction were eosinophilic esophagitis (n = 10) or reflux disease with or without peptic stenosis (n = 10), respectively. CONCLUSION: Bolus impaction is frequently correlated with eosinophilic esophagitis and reflux esophagitis; therefore, diagnostic workup should include esophageal biopsy sampling.

Gastrointestinal manifestation of systemic sclerosis--thickening of the upper gastrointestinal wall detected by endoscopic ultrasound is a valid sign.

OBJECTIVE: Gastrointestinal (GI) tract involvement has been observed in the majority of patients with SSc. This has been attributed to an accumulation of extracellular matrix within the GI walls. We visualized the walls of the oesophagus, stomach and duodenum with its layers and measured the thickness in SSc patients and control patients utilizing endoscopic ultrasound (EUS). METHODS: Twenty-five SSc patients and 25 controls were evaluated. In addition to analysis of clinical symptoms, endoscopy and EUS (20-MHz miniprobe) were performed. The thickness of the complete wall was measured, and the mucosa, submucosa and muscularis were evaluated separately. RESULTS: Clinical symptoms of SSc patients were dysphagia (14/25) and heartburn (19/25). Endoscopic findings were hiatal hernia (16/25), oesophagitis (6/25), amotility (19/25) and a dehiscent pylorus (15/25). In comparison with controls, SSc patients had significantly thicker oesophageal [SSc 1.619 (0.454) mm, control 1.392 (0.333) mm; P = 0.025], antral [SSc 1.876 (0.635) mm, control 1.599 (0.291) mm; P = 0.029] and duodenal [SSc 1.730 (0.522) mm, control 1.525 (0.222) mm; P = 0.039] walls. Predominantly, submucosa and muscularis were significantly thicker in SSc patients. The presence of dysphagia or amotility was significantly associated with the thickening of the GI walls. CONCLUSIONS: The EUS revealed a significant thickening of the walls of the upper GI tract in SSc patients. Predominantly, the submucosa and muscularis are enlarged. These results strengthen the hypothesis that increased matrix deposition is an important aspect in the pathogenesis of GI involvement in SSc.

A new grading system to evaluate the risk of endoscopic retrograde cholangiopancreatography.

BACKGROUND: The aim of our study was to develop a system to grade the risk of the procedures summarized under the term endoscopic retrograde cholangiopancreatography (ERCP). METHODS: In a controlled prospective study, we evaluated the early complications of ERCP in 526 consecutive patients at a single endoscopy center in a defined period. The relation between endoscopic procedures and related complications was analyzed for significance. A grading system based on significant risk factors and clinical implications was developed. RESULTS: Of the ERCP procedures, 29% were diagnostic and 71% therapeutic. A total of 45 complications occurred in 42 patients: pancreatitis (2%), perforation (1%), cardiorespiratory problems (0.6%), stent-related complications (0.5%), leakages (1.5%), and bleeding (3%). A native papilla was a significant risk factor for the development of complications (P = 0.046). On the basis of these findings, we defined five groups of ERCP-related complications: nonnative papillae with either diagnostic (A) or therapeutic interventions (B); native papillae with diagnostic (C) or therapeutic (D) interventions; and special therapeutic interventions (E). Complication rates differed significantly between individual groups, A versus D (P = 0.013), A versus E (P = 0.010), B versus D (P = 0.005), and B versus E (P = 0.003), as well as between A/B and C/D (P = 0.003). CONCLUSIONS: A grading system based on differentiating between native and nonnative papillae and diagnostic versus therapeutic procedures demonstrated significantly different complication rates. This grading system has the potential to predict the risk of ERCP-related complications.

Endothelial/lymphocyte activation leads to prominent CD4+ T cell infiltration in the gastric mucosa of patients with systemic sclerosis.

OBJECTIVE: Although gastrointestinal tract dysfunction is a common feature in patients with systemic sclerosis (SSc; scleroderma), few studies have addressed the pathogenetic mechanisms of gastrointestinal tract involvement in SSc. We previously showed that severe fibrosis and increased expression of profibrotic cytokines are important hallmarks in the gastric wall of patients with SSc. The aim of the present study was to investigate whether immune and/or microvascular abnormalities may account for tissue damage in gastric wall specimens obtained from patients with SSc. METHODS: Gastric biopsy samples from 27 patients with SSc and 15 healthy control subjects were analyzed by immunohistochemistry for CD45/leukocyte common antigen, CD3/T cells, CD4/T helper cells, CD8/cytotoxic T cells, CD20/B cells, CD14/monocytes, CD68/macrophages, cell adhesion molecules CD11a/lymphocyte function-associated antigen 1 (LFA-1), CD49d/very late activation antigen 4 (VLA-4), CD54/intercellular adhesion molecule 1 (ICAM-1), CD106/vascular cell adhesion molecule 1 (VCAM-1), CD31/platelet endothelial cell adhesion molecule 1, and vascular endothelial growth factor (VEGF). RESULTS: T cell infiltration was a prominent finding in gastric specimens from patients with SSc. The CD4+/CD8+ T cell ratio was significantly increased in SSc specimens compared with controls. T cells were found in both lymphocyte aggregates and diffuse infiltrates and strongly expressed the activation markers VLA-4, LFA-1, and ICAM-1. Endothelial cells showed corresponding surface activation with strong expression of VCAM-1 and ICAM-1. Mature B cells were frequently observed arranged in aggregates and rarely were seen in a diffuse pattern. Most lymphocyte aggregates lacked monocyte/macrophages. No difference in microvascular density was observed between SSc specimens and controls. Both SSc and control specimens showed weak or no expression of VEGF. CONCLUSION: Our findings provide the first evidence that endothelial/lymphocyte activation leading to prominent CD4+ T cell infiltration may play a key pathogenetic role within the gastric wall of patients with SSc and may represent an important therapeutic target.

A prospective, non-randomized phase II trial of Trastuzumab and Capecitabine in patients with HER2 expressing metastasized pancreatic cancer.

BACKGROUND: Pancreatic cancer is the fourth most common cause of cancer related death in Western countries. Advantages in surgical techniques, radiation and chemotherapy had almost no impact on the long term survival of affected patients. Therefore, the need for better treatment strategies is urgent. HER2, a receptor tyrosine kinase of the EGFR family, involved in signal transduction pathways leading to cell growth and differentiation is overexpressed in a number of cancers, including breast and pancreatic cancer. While in breast cancer HER2 has already been successfully used as a treatment target, there are only limited data evaluating the effects of inhibiting HER2 tyrosine kinases in patients with pancreatic cancer. METHODS: Here we report the design of a prospective, non-randomized multi-centered Phase II clinical study evaluating the effects of the Fluoropyrimidine-carbamate Capecitabine (Xeloda) and the monoclonal anti-HER2 antibody Trastuzumab (Herceptin) in patients with non-resectable, HER2 overexpressing pancreatic cancer. Patients eligible for the study will receive Trastuzumab infusions on day 1, 8 and 15 concomitant to the oral intake of Capecitabine from day 1 to day 14 of each three week cycle. Cycles will be repeated until tumor progression. A total of 37 patients will be enrolled with an interim analysis after 23 patients. DISCUSSION: Primary end point of the study is to determine the progression free survival after 12 weeks of bimodal treatment with the chemotherapeutic agent Capecitabine and the anti-HER2 antibody Trastuzumab. Secondary end points include patient's survival, toxicity analysis, quality of life, the correlation of HER2 overexpression and clinical response to Trastuzumab treatment and, finally, the correlation of CA19-9 plasma levels and progression free intervals.

Factors affecting cecal and ileal intubation time in colonoscopy.

BACKGROUND AND PURPOSE: The time required for a colonoscopy must be justified under economic aspects. The objective of this study was to analyze patient- and staff-related factors influencing the time for cecal and ileal intubation. PATIENTS AND METHODS: A prospective study was performed on 500 consecutive patients undergoing colonoscopy in 2005. The authors analyzed patient age, gender, height, weight, surgical history, the presence of liver cirrhosis and splenomegaly, the number of children given birth, the presence of colorectal cancer and inflammatory bowel disease, the quality of bowel preparation, sedation, and the experience of the attending colonoscopist, the nurse and the team as factors of possible relevance to cecal and ileal intubation time. RESULTS: The cecum was reached in 495/500 examinations (99%). Intubation of terminal ileum was possible in 477/500 patients (96%). Mean cecal and ileal intubation times were 10.5+/-10.2 min and 6.4+/-7.9 min, respectively. Time to cecal intubation was related to the experience of the endoscopist (p=0.009), the nurse (p=0.04) and the whole team (p=0.002), as well as to an adequate cleaning of the bowel (p=0.01). CONCLUSION: A short intubation time requires experienced staff in combination with an adequate cleaning of the bowel without reference to biological or pathologic factors except for colon-shortening surgery. The gain in examination quality by inspecting the terminal ileum comes to the cost of a prolongation of insertion time of 25-30% in experienced hands.

Intracellular localization is a cofactor for the phototoxicity of protoporphyrin IX in the gastrointestinal tract: in vitro study.

Photodynamic therapy (PDT) is a new treatment modality for solid tumors as well as for flat lesions of the gastrointestinal tract. Although the use of 5-aminolevulinic acid-induced protoporphyrin IX (PPIX) shows important advantages over other photosensitizers, the main mechanisms of phototoxicity induced are still poorly understood. Three human colon carcinoma cell lines with variable degrees of differentiation and a normal colon fibroblast cell line were used to generate a suitable in vitro model for investigation of photosensitizer concentration as well as the applied light dose. Also, the effects of intracellular photosensitizer localization on efficiency of PDT were examined, and cellular parameters after PDT (morphology, mitochondrial transmembrane potential, membrane integrity and DNA fragmentation) were analyzed to distinguish between PDT-induced apoptosis from necrosis. The fibroblast cell line was less affected by phototoxicity than the tumor cells to a variable degree. Well-differentiated tumor cells showed higher toxicity than less-differentiated cells. After irradiation, cell lines with cytosolic or mitochondrial PPIX localization indicate a loss of mitochondrial transmembrane potential resulting in growth arrest, whereas membrane-bound PPIX induces a loss of membrane integrity and consequent necrosis. Although the absolute amount of intracellular photosensitizer concentration plays the main determining role for PDT efficiency, data indicate that intracellular localization has additional effects on the mode of cell damage.

Detection of dysplastic lesions by fluorescence in a model of chronic colitis in rats after local application of 5-aminolevulinic acid and its esterified derivatives.

5-Aminolevulinic acid (ALA) and ALA ester-induced protoporphyrin IX (PPIX) fluorescence are used for photodynamic diagnosis and therapy with promising results. The aim of the present study was to investigate the detection of dysplastic lesions by fluorescence after topical application of ALA and different esterified derivatives in a model of chronic colitis in rats. In female CD rats chronic colitis was induced by oral application of 5% dextrane sulfate sodium. ALA was used at different concentrations (0.072 and 0.036 mol/L). ALA-methylester (m-ALA), ALA-hexylester (h-ALA) and ALA-benzylester (b-ALA) were used at a concentration of 0.003, 0.002 and 0.002 mol/L, respectively. Fluorescence was examined under blue light, and histological findings of fluorescent and nonfluorescent biopsy specimens were recorded. Using ALA at a concentration of 0.072 mol/L, all dysplastic lesions (8/8) showed fluorescence (sensitivity 100%). Specificity was low at 57%. Reducing the concentration to 0.036 mol/L resulted in a sensitivity of only 56% (5/9) with an increase in specificity to 76%. On using h-ALA, sensitivity was 60% (3/5) with a specificity of 51%. Using m-ALA and b-ALA, sensitivity values were 25% and 33%, and values for specificity were 62% and 63%, respectively. Despite a low number of dysplastic lesions, the results of this study indicate that ALA ester-induced PPIX fluorescence has the potential for the detection of premaligant lesions but was not superior to ALA. ALA esters were used in 18- to 36-fold lower concentrations compared with ALA.

Photodynamic diagnosis in the gastrointestinal tract.

Clinical data on photodynamic diagnosis for the detection of premalignant and malignant lesions in the gastrointestinal tract are encouraging so far. A major benefit of using autofluorescence is the lack of side effects because no sensitizer has to be applied.However, highly sophisticated detection systems are needed to enhance the weak autofluorescence-based fluorescent signal. New prototypes of autofluorescence video endoscopes are under way and will be decisive for further clinical use, especially because results of recently published studies have been disappointing.

Complicated wireless capsule enteroscopy in a patient with Crohn's disease.

An 18-year-old male experienced a first episode of Crohn's disease with inflammation of the colon, stenosis of small intestine and a fistula of the anal sphincter. After resection of the fistula and 30 cm of proximal ileum the patient remained free of symptoms under medication with azathioprine and mesalazine for 6 years. Then, blood in the stool occurred. Diagnostic work-up - gastroscopy and colonoscopy 2004 and 2006, magnetic resonance enteroclysis 2004 and 2006 and wireless capsule enteroscopy 2006 - revealed slight inflammation in the ileum but no bleeding source. The bleeding ceased, but after 2 uneventful years abdominal cramps appeared and diagnostic work-up (magnetic resonance enteroclysis, radiograph) located the capsule still in the terminal ileum proximal to an inflamed stenosis. Corticosteroids were subscribed for 4 weeks, but the capsule stayed in place. Surgery was discussed, but denied by the patient. Finally, the capsule could be taken out by double balloon enteroscopy.

[Impaction of a "sausage bread" in the esophagus--first manifestation of an eosinophilic esophagitis in a 17-year-old patient]. / Eine impaktierte "Wiener Semmel" im Osophagus--Erstmanifestation einer eosinophilen Osophagitis bei einem 17-jährigen Patienten.

A 17-year-old patient was transferred to the emergency room with an impacted food bolus by colleagues from the Department of Otorhinolaryngology. The examination of ear, nose and throat revealed significant amounts of saliva in both recessus piriformis, a radiologic examination of the esophagus showed a foreign body with a diameter of 1.6 cm in the region of the transitional zone of esophagus and stomach with a support level of the contrast medium. Clinical examination and laboratory tests showed no abnormalities. An emergency gastroscopy was performed. The foreign body, already evident in the barium swallow, was found in the distal esophagus. The foreign body was identified as a food bolus and gently advanced into the stomach with the aid of the gastroscope. In the stomach further food residues were detected and the examination was aborted because of increased risk of aspiration. On the next day, an elective gastroscopy was performed. Several biopsies were obtained from the esophagus because eosinophilic esophagitis (EE) was suspected due to clinical symptoms. Histological work-up showed a significant amount of eosinophilic granulocytes (> 15 eosinophils/HPF, 400 x) and reactive changes in the distal esophagus. Therefore, EE was diagnosed. Fluticasone therapy led to amelioration of symptoms and there was no evidence of recurring bolus impaction during follow-up.

Ischemic-like cholangiopathy with secondary sclerosing cholangitis in critically ill patients.

OBJECTIVES: Sclerosing cholangitis in critically ill patients (SC-CIP) is a newly described entity of severe biliary disease with progression to liver cirrhosis. The mechanisms leading to this form of cholangiopathy with stricture formation and complete obliteration of bile ducts are unknown. PATIENTS AND METHODS: In the last 2 yr, sclerosing cholangitis was diagnosed in 26 patients during or after their stay on the intensive care unit by ERCP and/or liver histology. Complete patient records were available for 17 patients. Histological evaluations of liver biopsies and of four explanted livers, parameters of cardiovascular and respiratory conditions, treatment modalities, and accompanying infections were analyzed to find further hints for the pathomechanisms leading to SC-CIP. RESULTS: With the beginning of cholestasis, the earliest endoscopic findings were intrahepatic biliary casts with impairment of the biliary flow and subsequent biliary infection, in most cases with Enterococcus faecium. Liver biopsy confirmed cholangitis and histology of explanted livers revealed ulcerated biliary epithelium with hemorrhagic exudates in the bile ducts. In the further course, progressive sclerosis with formation of multiple strictures of the bile ducts was observed. All patients suffered severe respiratory insufficiency with the need for mechanical ventilation (40.7+/-32.9 days). The PaO2/FiO2 ratio until beginning of cholestasis was 150.5+/-43.1. Half of the patients (9/17) were treated with high-frequency oscillatory ventilation and 12/17 patients by intermittent prone positioning. All patients required catecholamines for hemodynamic stabilization. CONCLUSIONS: SC-CIP is a severe and in most cases rapidly progressive complication of intensive care patients. Ischemic injury of the biliary tree with the formation of biliary casts and subsequent ongoing biliary infection due to multiresistant bacteria seem to be major pathogenic mechanisms in the development of this new entity of sclerosing cholangitis.