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Eine 50-jahrige Patientin wurde mit starksten kolikartigen, epigastrischen Schmerzen in der Notfallaufnahme nach hausarztlicher Zuweisung mit dem Verdacht einer Cholangitis vorstellig.

Gastric cancer is one of the most common cancers. Unfortunately, it is often diagnosed at the advanced stage International Union Against Cancer stage IV. This induced us to carry out an interdisciplinary analysis of this patient group with the Department of Internal Medicine 1. Our aim was to discuss cancers classified initially as unresectable in a meeting of the interdisciplinary tumor board after palliative chemotherapy, and to refer selected patients for surgery after establishing resectability. The outcome of the chemotherapy, operation method, complication rate, and long-term survival were analyzed. From 1999 to 2008, 76 patients with metastatic gastric cancer or carcinoma of the esophagogastric junction were discussed by the interdisciplinary tumor board of the University of Erlangen and classified initially as unresectable. The patients then received palliative chemotherapy according to the AIO regimen (weekly high-dose 5-fluorouracil/folinic acid [FU/FA] in a 24 h infusion), plus irinotecan. If the tumor was subsequently classified as resectable, the patient underwent either gastric resection or gastrectomy with DII–III dissection. Metastases were resected depending on their location (liver). Peritoneal carcinomatosis was treated additionally by HIPEC. Statistical analysis was with SPSSS version 20. Surgical and general complications and hospital mortality were acceptable. There were no cases of anastomotic leak, but one patient died of fulminant pneumonia. The R0 resection rate was 69 %, and four patients had long-term survival of more than 60 months. There were significant survival advantages. Metastatic gastric cancer or carcinoma of the esophagogastric junction can become resectable after downsizing the tumor with palliative chemotherapy. Long-term survival is achieved in some cases. Therefore, every patient with this type of cancer should be discussed by the interdisciplinary tumour board after palliative chemotherapy to provide him with a chance of cure after re-evaluation.

This study aims to evaluate adherence to guidelines of antiemetic prophylaxis and frequency of chemotherapy-induced nausea and vomiting (CINV) in the palliative first-line treatment of colorectal cancer (CRC) patients in Northern Bavaria.We collected detailed information on chemotherapy and supportive drugs in 103 patients within a prospective observational study. The study was conducted to determine quality of care within an interdisciplinary context (first endpoint) and direct costs of palliative treatment for patients with CRC between 2006 and 2010 (second endpoint, Emmert et al. (Eur J Health Econ, 2012) [1]). In this paper, we evaluate adherence to Multinational Association of Supportive Care in Cancer (MASCC) 2006 recommendations for prophylaxis of CINV during the first administration of chemotherapy as well as incidence and grade of CINV within 120 h thereafter.Of the patients studied, 95 patients (92%) received moderately emetogenic (oxaliplatin- and/or irinotecan-containing combined chemotherapy treatment) and eight (8%) received low emetogenic chemotherapy (either 5-fluorouracil (5-FU) or capecitabine monotherapy). Antiemetic prophylaxis could be assessed in 101 out of 103 (98%) of patients. MASCC-recommended antiemetic prophylaxis was prescribed in three patients (3%). Nonadherence was mainly caused by omission of dexamethasone. Nausea and/or vomiting occurred in 18 patients (18%) within a 120-h period. All documented episodes were grade 1 or 2 according to the Common Toxicity Criteria of the National Cancer Institute. None of these patients received the recommended prophylaxis for CINV. In only one patient, antiemetic prophylaxis was intensified during the next chemotherapy application.In the Integrated Health Care in the Palliative Treatment of Colorectal Carcinoma (IVOPAK) I Project, adherence to the MASCC clinical recommendations was very poor. Extent of CINV in this patient population seems to be underestimated. There is an urgent need to improve clinicians' awareness of this patient-relevant side effect.

Aim Perforation occurs rarely after colonoscopy, but is associated with high morbidity and mortality. In this study, we assessed the perforation rate in our hospital, its clinical diagnosis and the long-term outcome. Method During the study period, 7535 examinations were performed, of which 4830 were diagnostic and 2705 therapeutic. The latter included polypectomy, endoscopic mucosal resection (EMR), endoscopic submucosal dissection (ESD), dilatation and argon plasma coagulation (APC). Results Overall, 25 (0.33%) perforations occurred with two (0.026%) procedure-related deaths. Seven (0.14%) perforations occurred during a diagnostic procedure and 18 (0.67%) occurred during a therapeutic procedure. Dilation, submusous resection (SMR) and APC accounted for more perforations than polypectomy or diagnostic colonoscopy. Pre-existing gastrointestinal disease was present in 24 (96%) perforations. Three (12%) patients were treated conservatively and 22 (88%) underwent surgery. The site of perforation was closed by suture in four (18%) patients and resected with colonic anastomosis in five (23%) patients. Two patients underwent endoscopic clipping. A stoma was created after resection in 13 (59%) patients. Conclusion Death from perforation after colonoscopy is rare, occurring in 1/3500 examinations. The risk is increased in therapeutic colonoscopy and in the presence of previous gastrointestinal disease. Dilatation, SMR and APC appeared to confer a higher risk of perforation than polypectomy or diagnostic colonoscopy.

Introduction: The prognostic outlook for patients suffering from pancreatic cancer is generally poor. Particularly in cases of advanced and metastatic disease, long-term relapse-free survival may be achieved only in a few cases. Case Report: A 45-year-old patient presented with metastatic pancreatic cancer. Liver metastases had been intra-operatively confirmed by histology. Prior to initiating treatment, a portacath was surgically implanted. Subsequently, the patient received a weekly dose of 1,000 mg/m2 gemcitabine combined with 2,000 mg/m2 high-dose 5- fluorouracil as a 24-hour infusion for palliative treatment. As the patient was suffering from a stenosis of the ductus hepaticus communis, an endoprosthesis was primarily implanted. After 18 applications of chemotherapy during which only low toxic side effects such as nausea, vomiting and alopecia (NCI-CTC grade 1) presented, a partial remission of the primary tumor was observed. In the course of chemotherapy treatment, the carbohydrate antigen 19-9 tumor marker value normalized. Thus, the interdisciplinary tumor board of the University of Erlangen decided to perform a laparoscopy to evaluate the status of liver metastases after palliative chemotherapy treatment. Subsequently, the primary tumor could be completely resected (pT2, pN0, pM0, L0, V0, G2, R0); liver metastases were not observed. Eight years after the initial diagnosis, the patient is relapse-free, professionally fully integrated and presents with an excellent performance status. Conclusion: Patients suffering from metastatic pancreatic cancer may benefit from treatment combinations with palliative intent. In singular cases, patients may even have a curative treatment option, provided a close interdisciplinary collaboration exists.

Summary Background The aim of this retrospective study was to evaluate the efficacy and safety of weekly high-dose 5-fluorouracil (5-FU)/folinic acid (FA) as 24-h infusion (AIO regimen) plus irinotecan in patients with histologically proven metastatic gastroesophageal adenocarcinoma (UICC stage IV). Material/Methods From 08/1999 to 12/2008, 76 registered, previously untreated patients were evaluable. Treatment regimen: irinotecan (80 mg/m2) as 1-h infusion followed by 5-FU (2000 mg/m2) combined with FA (500 mg/m2) as 24-h infusion (d1, 8, 15, 22, 29, 36, qd 57). Results Median age: 59 years; male/female: 74%/26%; ECOG ≤1: 83%; response: CR: 1%, PR: 16%, SD: 61%, PD: 17%, not evaluable in terms of response: 5%; tumor control: 78%; median OS: 11.2 months; median time-to-progression: 5.3 months; 1-year survival rate: 49%; 2-year survival rate: 17%; no evidence of disease: 6.6%; higher grade toxicities (grade 3/4): anemia: 7%, leucopenia: 1%, ascites: 3%, nausea: 3%, infections: 12%, vomiting: 9%, GI bleeding of the primary tumor: 4%, diarrhea: 17%, thromboembolic events: 4%; secondary metastatic resection after downsizing: 16 patients (21%), R-classification of secondary resections: R0/R1/R2: 81%/6%/13%, median survival of the 16 patients with secondary resection: 23.7 months. Conclusions Combined 5-FU/FA as 24-h infusion plus irinotecan may be considered as an active palliative first-line treatment accompanied by tolerable toxicity; thus offering an alternative to cisplatin-based treatment regimens. Thanks to efficient interdisciplinary teamwork, secondary metastatic resections could be performed in 16 patients. In total, the patients who had undergone secondary resection had a median survival of 23.7 months, whereas the median survival of patients without secondary resection was 10.1 months (p≤0.001).

In the majority of patients with oesophageal carcinoma, curative treatment proves to be impossible when diagnosis was established; therefore, most of the patients are candidates for palliative chemotherapy. The aim of this phase II study was to evaluate the efficacy and safety of 5-fluorouracil/folinic acid (AIO regimen) plus irinotecan in patients with locally advanced or metastatic carcinoma of the oesophagus. The methods used a prospective phase II trial, start: November 2002; patients: n=25; chemotherapy: irinotecan (80 mg/m2) as a 1-h infusion and 5-fluorouracil (2000 mg/m2) with sodium folinic acid (500 mg/m2) as a 24-h infusion on days 1, 8, 15, 22, 29 and 36, repeated on day 57. Last date of evaluation: 28 February 2007; n=24; adenocarcinoma: n=13, squamous cell carcinoma (SCC): n=11; UICC III/IV: 3/21; grading G1/G2/G3/G4: 0/8/12/4; median age: 58 years (range 44-75); men/women: 19/5; Eastern Cooperative Oncology Group index 0/1/2: 3/17/4; applications: 460. Higher-grade toxicity: grade 3 diarrhoea: n=2, grade 4 diarrhoea: n=1, grade 4 vomiting: n=1, grade 4 nausea: n=1, grade 3 fatigue: n=1, grade 3 hyponatraemia: n=2, grade 4 elevation of creatinine: n=1, thrombosis of the vena subclavia: n=1, ischaemic lesion of the brain stem: n=1. Three patients died after two chemotherapeutic applications because of high tumour burden. Evaluable for response: n=19. Partial response: n=8 (33%), stable disease: n=9 (38%), progressive disease: n=2 (8%), not evaluable: n=5 (21%). Time-to-progression: 6.6 months (range 1.6-24.6). Total median survival: 13.6 months (median survival of adenocarcinoma: 20.3 months, median survival of SCC: 10.0 months). Secondary resection (R0): n=3. In oesophageal carcinomas, the AIO regimen plus irinotecan is excellently manageable as an outpatient treatment and shows efficacy in adenocarcinomas and SCCs of the oesophagus.

Background. After approval of bevacizumab in Germany in 2005 for the treatment of unresectable advanced or refractory colorectal cancer (CRC), this observational cohort study was initiated to assess the efficacy and safety of bevacizumab with various chemotherapy regimen in patients with metastatic CRC (mCRC).Material and methods. To facilitate enrolment of a typical mCRC population, eligibility criteria were minimised. Choice of chemotherapy regimen was at the physicians’ discretion, but influenced by current registration status. Predefined endpoints were treatment characteristics, response rate, progression-free survival (PFS), overall survival (OS) and adverse events assessed as potentially related to bevacizumab treatment. Patients were followed for up to four years.Results. In total 1777 eligible patients were enrolled at 261 sites from January 2005 to June 2008. Median age: 64 years (range 19–100); male 62%; ECOG performance status 0–1/≥ 2 89%/11%. Chemotherapy choice was fluoropyrimidine (FU) 12%, FU/oxaliplatin 18%, FU/irinotecan 64%, no chemotherapy concurrent to bevacizumab 2% and other 4%. Best investigator-assessed response rate was 60% (complete response 10%, partial response 51%). Median PFS was 10.2 months and median OS was 24.8 months.Conclusions. The efficacy and safety profile of bevacizumab in this population of mCRC patients with different chemotherapy regimens is consistent with that observed in other patient registries/non-randomised trials and also corresponds well with data from similar treatment arms of phase III trials.

Methylation of promoter regions and frameshift mutations in microsatellites of the coding sequence (CDS) of genes are frequently associated with loss of expression in microsatellite instable (MSI) colorectal carcinoma. In a panel of 40 MSI and 24 microsatellite stable (MSS) colorectal tumours as well as six cultured colorectal carcinoma cell lines hypermethylation of the TIMP3-promoter was found in 28% of MSI and 25% of MSS tumours, respectively. Additionally, three MSI tumours and one cell line displayed instability of a C7-repeat located in the CDS of the TIMP-3 gene. TIMP-3 fulfils all important criteria for being a target gene in the mutator pathway. Thus, TIMP-3 might be a factor of general importance for colorectal carcinogenesis.

At present, systemic treatment is not generally recommended for advanced biliary tract and gall bladder carcinomas. In particular cases, however, it may be justified to consider systemic chemotherapy treatment. In four cases we investigated the efficacy of palliative systemic treatment in metastatic biliary tract and gall bladder adenocarcinomas. Similar to the proceedings in a phase II study for metastatic pancreas adenocarcinomas, four patients with advanced biliary tract and gall bladder adenocarcinomas received a combination treatment of gemcitabine (GEM) and weekly high-dose 5-fluorouracil (5-FU) as a 24-h infusion. Altogether, the four patients received 96 chemotherapy applications. The palliative chemotherapy was tolerated well. In one patient, leukocytopenia (toxicity grade III) and thrombocytopenia (toxicity grade III) occurred. In three patients, the palliative systemic treatment led to stable disease, partly with a significant decrease of the CA 19-9 tumor marker, and in one patient to partial remission (PR). The survival times in these four patients were 6, 10, 17 and 26 months. Even in the case of PR, a curative hemihepatectomy right could be achieved after 'downsizing'. We conclude that in the four case studies, the applied palliative combination treatment based on GEM and 5-FU proved to be effective. However, future multicenter studies will be necessary to determine the significance of palliative chemotherapy in biliary tract and gall bladder carcinomas.

The most commonly used treatment in the palliative first-line therapy of metastatic pancreatic adenocarcinoma is the Gemcitabine (Gem) monotherapy, while several combination therapies are currently being tested in clinical trials. With regard to pancreatic cancer, a palliative second-line therapy has not been established, yet. The four patients presented in this paper received a palliative second-line therapy with Oxaliplatin (L-OHP), Gem and high-dose 5-Fluorouracil (5-FU) as a 24-h infusion after a first-line therapy with Gem and weekly high-dose 5-FU as a 24-h infusion. During second-line therapy, four patients received 67 chemotherapy applications, which were well tolerated. As severe symptom of toxicity, thrombocytopenia (CTC toxicity grade 4) was observed in one patient. As a result of second-line therapy, stable disease (SD) with a significant decrease of CA 19 - 9 was achieved in three patients and partial remission (PR) in one patient. After palliative first- and second-line treatment the survival time of the patients was 9, 9, 15 and 20 months. Currently, a multicentre phase I study has been started aiming at an optimisation of the three-drug combination dosage.

Background & Aims Senescence prevents cellular transformation. We investigated whether vascular endothelial growth factor (VEGF) signaling via its receptor, VEGFR2, regulates senescence and proliferation of tumor cells in mice with colitis-associated cancer (CAC). Methods CAC was induced in VEGFR2 ΔIEC mice, which do not express VEGFR2 in the intestinal epithelium, and VEGFR2 fl/fl mice (controls) by administration of azoxymethane followed by dextran sodium sulfate. Tumor development and inflammation were determined by endoscopy. Colorectal tissues were collected for immunoblot, immunohistochemical, and quantitative polymerase chain reaction analyses. Findings from mouse tissues were confirmed in human HCT116 colorectal cancer cells. We analyzed colorectal tumor samples from patients before and after treatment with bevacizumab. Results After colitis induction, VEGFR2 ΔIEC mice developed significantly fewer tumors than control mice. A greater number of intestinal tumor cells from VEGFR2 ΔIEC mice were in senescence than tumor cells from control mice. We found VEGFR2 to activate phosphatidylinositol-4,5-bisphosphate-3-kinase and AKT, resulting in inactivation of p21 in HCT116 cells. Inhibitors of VEGFR2 and AKT induced senescence in HCT116 cells. Tumor cell senescence promoted an anti-tumor immune response by CD8 + T cells in mice. Patients whose tumor samples showed an increase in the proportion of senescent cells after treatment with bevacizumab had longer progression-free survival than patients in which the proportion of senescent tumor cells did not change before and after treatment. Conclusions Inhibition of VEGFR2 signaling leads to senescence of human and mouse colorectal cancer cells. VEGFR2 interacts with phosphatidylinositol-4,5-bisphosphate-3-kinase and AKT to inactivate p21. Colorectal tumor senescence and p21 level correlate with patient survival during treatment with bevacizumab.

Nuclear factor-kappa B (NF-kappaB) is a critical transcription factor for the inducible expression of multiple genes involved in inflammation. NF-kappaB is sequestered in the cytoplasm by inhibitory IkappaB proteins. Extracellular stimuli, notably interleukin-1beta (IL-1beta) and tumor necrosis factor alpha (TNF-alpha) activate NF-kappaB nuclear translocation via IkappaB phosphorylation and degradation. Since previous reports suggest that the short chain fatty acid butyrate has antiinflammatory properties, the effects of butyrate on NF-kappaB nuclear translocation in human epithelial cells (HeLa229) were tested. In cells pretreated with butyrate, a time- and dose-dependent inhibition of IL-1beta-mediated NF-kappaB nuclear translocation was observed. However, IkappaB alpha phosphorylation and degradation occurred rapidly in both butyrate pretreated and nonpretreated cells, respectively. These data indicate that inhibition of IL-1beta-induced NF-kappaB activation by butyrate does not require an intact IkappaB alpha protein.

Short-chain fatty acids (SCFAs) derived from bacterial fermentation of complex carbohydrates are preferred luminal nutrients of the colonic mucosa. Starvation of colonocytes through lack or impaired metabolism of luminal SCFAs may be a cofactor in the pathogenesis of ulcerative colitis.A detailed histological evaluation of colonic biopsy specimens was performed in patients with active distal ulcerative colitis who were treated with rectal enemas containing a mixture of SCFAs, n-butyrate alone or saline placebo. Together with light microscopic parameters of mucosal inflammation, the pattern of crypt cell proliferation (proliferating cell nuclear antigen) and the mucosal activity of factor XIII were assessed.Butyrate reduced the density of polymorphonuclear leucocytes in the lamina propria (4 weeks: P = 0.063; 8 weeks: P = 0.091); other inflammatory parameters remained unchanged. Both butyrate and the SCFA mixture reduced significantly the number of proliferating cells in the upper 40% of crypts. Tissue factor XIII activity in active ulcerative colitis was significantly lower than in mucosa from normal colons; however, it was not affected by SCFA or butyrate irrigation.SCFAs and butyrate have a more marked effect on crypt cell proliferation than on parameters of inflammation in patients with active ulcerative colitis.

Inflammatory pseudotumors (IPT) form a group of etiologically, histologically, and biologically heterogeneous tumefactive lesions that are histologically characterized by prominent inflammatory infiltrates. IPT has been described in various organs including the lungs, bladder, liver, spleen, heart, and others. It may mimic a malignant tumor clinically and radiologically. We report a case of a 26-year-old woman with an ALK1- negative IPT (7 cm in maximal diameter) mainly located in the 12th right back muscles, surrounding a fractured rib. Histologically, the tumor consisted of an inflammatory infiltrate composed predominantly of diffusely distributed lymphoplasmacytic cells and stromal fibroblasts associated with focal obliterative phlebitis. Conservative steroid treatment resulted in complete remission and the patient remained disease-free for more than 1 year later. To our knowledge this is the first report of IPT involving the skeletal back muscle and complete resolution under corticosteroid treatment.

To estimate the costs of palliative care for colorectal cancer (CRC) from the perspective of German statutory health insurance and to measure the patients’ quality of life (QoL) for a 2-year time period. A prospective observational multicentre study was carried out to estimate the direct costs of care over a 2-year period. Case report forms, medical records, and claims data were all applied to document medical and resource usage data in real-world settings. QoL was measured by using the Short Form-12 Health Survey. In total 101 patients (mean age 67.09 ± 11.13 years, 68 % male) from 12 different settings were included. The mean costs per patient during the 1st and 2nd years were calculated to be 42,361€ and 32,023€, respectively. Highest mean costs were calculated for the second quarter, which reached an amount of 12,900€ (95 % CI: 11,127€–14,673€). Mean physical summary scores and mean mental summary scores were 41.8 and 49.7, respectively. This is the first study assessing the costs of palliative care and the quality of life of patients with CRC in real-world health-care delivery in Germany. It could be shown that CRC treatment represents an enormous economic burden to the German health-care system. Increased efforts in promoting effective and efficient treatment options, or performance-based medication reimbursement schemes, might be helpful in reducing the costs.

The aim of this study was to evaluate the efficacy and toxic side effects of combined gemcitabine plus weekly high-dose 5-Fluorouracil (5-FU) as 24h-infusion in patients with metastatic pancreatic cancer (UICC IV) as validation group of an earlier phase II study. Primary endpoints were to assess the response and tumour control rate.This study comprised 60 prospectively registered patients with metastatic pancreatic cancer (UICC IV). A locally advanced disease was defined as exclusion criteria. The treatment schedule was weekly gemcitabine (1.000 mg/m(2)) as a 0.5h-infusion combined with 5-FU (2.000 mg/m(2)) as a 24h-infusion on day 1, 8 and 15 every 28 days.Response rate (CR+PR) was achieved in 7% of the patients, tumour control rate (CR+PR+SD) was achieved in 59%. Median time-to-progression was 4 months, median overall survival was 7.3 months (95% CI 5.4-9.1). The median survival of patients with normal CEA value was 10.6 months (95% CI 7.8-13.4); with a normal CA 19-9 median survival was 10.1 months (95% CI 4.6-15.7) and with ECOG performance status 0 median survival was 10.1 months (95% CI 8.6-15.3). As higher grade toxicity (grade 3/4) leukopenia (15%), anaemia (10%) and thrombopenia (5%) were observed. Nausea and diarrhea (grade 3/4) occurred in 5% of the patients and vomiting in 2%.The administration of gemcitabine and 5-FU as a 24h-infusion is feasible and offers good tumour control rate accompanied by tolerable toxicity. The subgroup of patients with a good performance status (ECOG 0) and tumour markers within the normal range benefit from the gemcitabine combination therapy.

In 2003 Wein et al. published data after a short median follow up (23 months). Here we report on the long-term results.The patients (n=20) received a neoadjuvant treatment regimen comprising biweekly 85 mg/m2 oxaliplatin (L-OHP) (2h-infusion, d 1, 15, 29 qd 57) and 500 mg/m2 calcium folinic acid (FA) (1-2h-infusion, d 1, 8, 15, 22, 29, 36 qd 57) followed by 2600 mg/m2 5-Fluorouracil (5-FU) (24h-infusion, d 1, 8, 15, 22, 29, 36 qd 57). Two cycles of chemotherapy were administered, with a third being added when the treatment was well tolerated. Thereafter, curative resection of the liver metastases was attempted.After neoadjuvant therapy, imaging procedures revealed complete remission in 2 patients (10%) and partial remission in 18 patients (90%). Diarrhea (Common Toxicity Criteria toxicity grade 3) was observed in 6 patients (30%) as main symptom of toxicity, followed by vomiting in 3 patients (15%). Higher grade sensomotoric neuropathy did not present. The curative resectability rate (R0) was 80%. In 9 out of 18 patients (50%) undergoing surgical intervention minor postoperative complications occurred. No postoperative mortality was observed. Over a median follow up of 45,5 months the median survival of all patients is 3.0 years and the 5-year overall survival rate is 40%. The 5-year disease-free survival rate is 25%.Neoadjuvant treatment with 5-FU combined with FA and L-OHP proved to be highly effective and well tolerated. Disease-free survival rates and median overall survival rates are promising.

In 40% of all cases of Crohn's disease fistulas emerge during the course of disease. Nevertheless, acne inversa has to be taken into account as an infrequent differential diagnosis. Infliximab as an antibody against the pro-inflammatory mediator TNF-alpha is active in cases of acute Crohn's disease, concomitant fistulas and cutaneous manifestations.We report on the case of a 54-year-old patient suffering for five years from a severe suppurative fistuling cutaneous disease concomitant to Crohn's disease. At the start of treatment the histological findings of a specimen presented chronically fibrosing lymphoplasmacellular dermatitis with both a very high number of plasma cells and a burrow-like fistula system. Due to superinfection the treatment was at first based on the administration of intravenous and oral doses of antibiotic agents, followed by a treatment course of 14 months with methotrexate and seven applications of infliximab. During the Crohn's disease, which was accompanied by persisting concomitant discomforts, an extensive surgical sanitation of the fistulous tracts was performed. Acne inversa was diagnosed in the subsequent histological analysis of the operative specimen.Acne inversa is a very rare cutaneous disease. Several case reports describe the successful treatment of acne inversa concomitant to Crohn's disease using anti-TNF-alpha-antibodies. The long-term course of the case presented here shows that the non-response to infliximab might be caused by both the long duration and the distinct grade of seriousness of the acne inversa.

13528 Background: During the last years due to the application of Irinotecan, Oxaliplatin and “biologicals” for the first- and secondline treatment of CRC in palliative situation the efficacy of palliative treatment has considerably improved with an acceptable toxicity. The achievements of secondary metastatic resection after downsizing by palliative treatment have increasingly become the focus of interest in palliative patients and opened up new ways in terms of curative options (Folprecht et al. 2005; Wein et al. 2001). Here, we analyse the influence of different departments on the resection rate after palliative treatment. Methods: A prospective phase III trial in metastatic CRC with systemic treatment by 5-FU/sodium FA as a 24h-infusion (AIO) versus AIO plus Oxaliplatin followed by secondary metastatic resection. Trial start: 2000; end of trial: 2005. Randomized patients: n = 240 by 5 centers experienced in clinical trials. In order to achieve a homogeneous patient group, non-resectability of distant metastases was required according to pre-defined criteria. Stratification characteristics: In accordance to the participating departments; ECOG index 0.1 vs 2. Involvement of the hepatic tumour extension 25% vs other localisation; organ manifestation 1 vs > 1. Inclusion criteria: Definitively non-resectable metastases. Palliative first-line treatment: Histologically proven adenocarcinoma of the colon or rectum, unambiguous enlargement of metastatic masses in objective imaging procedures. At least one bidimensionally measurable tumour lesion. Age: > 18, < 75 years. Exclusion criteria: Concomitant treatment with other anti-neoplastic substances. Sensoric neuropathy. Results: Resected/randomized patients of 176 currently evaluable patients, both treatment groups combined: department (dep.) 01: 0/26 (0%), dep. 02: 10/27 (37.0%), dep. 03: 21/68 (30.9%), dep. 04: 8/43 (18.6%), dep. 05: 1/12 (8.3%), total: 40/176 (22.7%). Although in the total population, a remarkable resection rate could be achieved, the variation between the departments is high (p=.0043 for differences between departments). Conclusions: The resection rate after palliative CRC treatment essentially depends on the department. No significant financial relationships to disclose.

14109 Background: At the moment of establishing the diagnosis, in approximately 50–60% of the patients with esophageal carcinoma only palliative treatment is possible due to either a locally advanced tumour growth or due to distant metastases. While adenocarcinomas of the esophagogastric junction are increasingly treated like gastric carcinomas, no palliative standard regimen is established for advanced squamous carcinomas of the oesophagus. The question should be answered whether the AIO regimen plus Irinotecan may achieve similarly positive results in esophageal carcinomas as in gastric carcinomas. Methods: Prospective phase II trial, patients: n=20, trial start: 03/2003, chemotherapeutic regimen: Irinotecan (80 mg/m2 i.v. as 1h-infusion; d 1, 8, 15, 22, 29, 36, qd 57) as well as folinic acid (500 mg/m2 i.v.) together with 5-Fluorouracil (2000 mg/m2 i.v.; d 1, 8, 15, 22, 29, 36, qd 57) as 24h-infusion via port catheter. Results: n=16 (adenocarcinomas: n=8, squamous epithelial carcinomas: n=8); median age: 59,3 (44–72) years; men/women: 13/3; ECOG 0/1/2: 4/11/1; chemotherapeutic applications: 314. Evaluable in terms of toxicity: n=16. Higher grade toxicity: grade III diarrhea: n=2, grade III hyponatremia: n=1, thrombosis of the vena subclavia: n=1, grade III stomatitis: n=1, ischemic lesion of the brain stem: n=1. Two patients died after 2 chemotherapeutic applications with known peritoneal carcinomatosis and high tumour burden. Evaluable in terms of response: n=13. PR: n=7 (54%), SD: n=4 (31%), PD: n=2 (15%). Conclusion: The AIO regimen plus Irinotecan is excellently manageable on an outpatient basis in a multimorbid patient group and shows high efficacy in both adenocarcinomas and squamous epithelial carcinomas of the oesophagus. Final results, however, particularly in terms of median survival, still remain to be seen. No significant financial relationships to disclose.

Desmoid tumors, also known as aggressive fibromatosis, occur with an incidence of 10 to 15 percent in patients affected by familial adenomatous polyposis, an autosomal inherited disease caused by germline mutations in the APC gene. However, sporadic forms with no hereditary background exist. The aim of this study was to find out whether there are APC germline mutations in apparently sporadic desmoid tumor patients without clinical or familial signs of familial adenomatous polyposis but with a family history of colorectal carcinoma in at least one family member. Genomic DNA and mRNA were isolated from peripheral blood leukocytes of index patients of eight nonrelated families. Mutation screening was performed using reverse transcriptase polymerase chain reaction–based protein truncation test for APC exons 1–14. The large APC exon 15 was scrutinized by the protein truncation test of four overlapping genomic fragments. Additionally, genomic DNA from five desmoid tumors was analyzed for loss of heterozygosity at D5S346 close to the APC locus. No translational stop mutations typical for familial adenomatous polyposis could be found in the APC gene in any of the analyzed blood samples from the desmoid tumor patients. Additionally, no loss of heterozygosity at D5S346 was found in four of five desmoids; one tumor was not informative. These results may suggest that patients with sporadic desmoids and no clinical signs of familial adenomatous polyposis detected on careful examination, esophagogastroduodenoscopy, and complete colonoscopy do not need to be tested routinely for germline mutations of the APC gene. However, as large studies dealing with this problem are absent, it might be more time and cost effective to perform an APC mutational analysis instead.

Autoimmune hepatitis is rarely described in combination with antiphospholipid syndrome. So far, only cases have been presented where the secondary antiphospholipid syndrome occurred as an effect of autoimmune hepatitis. We report on a 56-year-old Caucasian female with a history of thrombosis, thrombocytopenia and the detection of anti-cardiolipin antibodies. Interestingly, a few years later the patient developed liver failure with highly elevated liver enzymes. The immunological antibody pattern verified the diagnosis of type I autoimmune hepatitis, and immunosuppressive therapy led to the recovery of the patient. Thus, we present the first case of autoimmune hepatitis as a consequence of primary antiphospholipid syndrome.

INTRODUCTION To date, only few reports are available on patients with esophageal carcinoma containing a tracheoesophageal fistula under chemotherapy. CASE REPORT A 56-year-old patient presented to the hospital with a stenosing squamous cell carcinoma of the esophagus containing a tracheoesophageal fistula 3 cm above the carina. After placement of a Port-a-Cath and adequate hydration he received weekly 500 mg/m (2) i. v. folinic acid (FA) as a 1 - 2-hour infusion and 2000 mg/m (2) 5-fluorouracil (5-FU) as a 24-hour infusion (24-h inf.) (AIO regimen) with prior application of bi-weekly 50 mg/m (2) i. v. cisplatin. A tracheal Y-Dumont metallic stent was inserted prior to initiating systemic treatment. The patient's alimentation was completely parenteral. After three cycles of chemotherapy (six months) the patient revealed complete remission (CR) with closure of the tracheoesophageal fistula. The tracheal Y-Dumont stent could be removed and the patient had oral alimentation restored. 29 months after initiating treatment he is without evidence of disease. CONCLUSION Patients with esophageal carcinoma containing a tracheoesophageal fistula might benefit from chemotherapy and should not be generally excluded from systemic treatment.

Eine 77-jahrige Patientin wurde mit Belastungsdyspnoe und Druckgefuhl im rechtsseitigen Abdomen aufgenommen. Sie berichtete, dass ihr Bauchumfang seit zwei Jahren zugenommen hatte. An relevanten Vorerkrankungen waren ein Parkinson-Syndrom, eine arterielle Hypertonie und ein Diabetes mellitus Typ 2 bekannt. Die korperliche Untersuchung ergab ein blasses Hautkolorit und auskultatorisch sowie perkutatorisch einen Zwerchfellhochstand rechts mit Dampfung des Atemgerausches und mittelblasigen Rasselgerauschen bei einer Atemfrequenz von 16/min. Abdominell war rechtsseitig eine Raumforderung palpabel. Die Laborwerte ergaben eine leichtgradige Anamie (Hamoglobin 11,4 g/dl, Norm 12–16) und eine Erhohung des C-reaktiven Proteins (110 mg/l, Norm < 5) und der g-GT (406 U/l, Norm < 38). In der Abdomensonographie wurde die Leber vergrosert, mit komprimierten Lebervenen dargestellt. Mehrere teils konfluierende Zysten konnten in beiden Leberlappen nachgewiesen werden. Die groste Leberzyste ging vom rechten Leberlappen aus. Zysten in anderen Organen konnten sonographisch ausgeschlossen werden. In der Abdomen-CT wurde die monstrose, rechtsseitige Zyste mit 30 x 20 cm gemessen, und es konnte die Verdrangung der rechten Niere nach medial-kaudal abgebildet werden (Abbildung 1). Im Rontgen-Thorax waren eine rechtsseitige Mittellappenteilatelektase und ein Zwerchfellhochstand rechts zu sehen. Bei erhohten Entzundungsparametern und Verdacht auf Pneumonie rechts wurde eine antibiotische The

3561 Background: The FOLFIRI followed by FOLFOX6 (or vice versa) schedule has been considered as the gold standard of sequential treatment in CRC (Tournigand C. JCO 2004). In contrast to those bi-weekly schedules, the wide-spread weekly chemotherapy administration (e.g. AIO regimen), has not been investigated as yet for second-line treatment. The AIO + IRI schedule has provided promising results in the first-line treatment of CRC (Köhne C.-H. JCO 2005). Therefore, we now investigated the efficacy and toxicity of this schedule in second-line treatment in a phase II study. Methods: From 5/02 to 6/10, 60 palliative patients (pts.) with histologically proven CRC were enrolled in an oligocentric phase II study based on the following regimen: weekly IRI (80 mg/m2 i.v.) as 1h-infusion (inf.): d1, 8, 15, 22, 29, 36, qd 57 followed by 5-FU (2000 mg/m2 i.v.) combined with sodium folinic acid (500 mg/m2, d1, 8, 15, 22, 29, 36, qd 57) as a 24h-inf. via port-a-cath. This study focused on the efficacy and toxicity of second-line treatment with AIO + IRI. Results: Last date of evaluation: November 30, 2012; evaluable for efficacy: n = 58 pts., evaluable for toxicity: n = 59 pts.; men/women: 28/72%; median age: 65y; primary tumor location: rectum/colon: 45/55%.; toxicity data: higher grade toxicity (grade 3-4): leukocytopenia: 5.1%; thrombocytopenia: 1.7%; vomiting: 3.4%; diarrhea: 13.5%; hand-foot-syndrome: 1.7%; alopecia (grade 2) 3.4%; efficacy data: PFS: 4.2 m; median OS 14.2 m, RR: 10%; AIO + IRI following AIO + L-OHP achieved a median OS of 25.0 months. Conclusions: In the field of second-linetreatment of CRC the AIO plus IRI regimen offers both a favorable toxicity profile and promising results in terms of efficacy compared with the FOLFIRI regimen.

AIM: To evaluate double balloon enteroscopy (DBE) in post-surgical patients to perform endoscopic retrograde cholangiopancreatography (ERCP) and interventions. METHODS: In 37 post-surgical patients, a stepwise approach was performed to reach normal papilla or enteral anastomoses of the biliary tract/pancreas. When conventional endoscopy failed, DBE-based ERCP was performed and standard parameters for DBE, ERCP and interventions were recorded. RESULTS: Push-enteroscopy (overall, 16 procedures) reached enteral anastomoses only in six out of 37 post-surgical patients (16.2%). DBE achieved a high rate of luminal access to the biliary tract in 23 of the remaining 31 patients (74.1%) and to the pancreatic duct (three patients). Among all DBE-based ERCPs (86 procedures), 21/23 patients (91.3%) were successfully treated. Interventions included ostium incision or papillotomy in 6/23 (26%) and 7/23 patients (30.4%), respectively. Biliary endoprosthesis insertion and regular exchange was achieved in 17/23 (73.9%) and 7/23 patients (30.4%), respectively. Furthermore, bile duct stone extraction as well as ostium and papillary dilation were performed in 5/23 (21.7%) and 3/23 patients (13.0%), respectively. Complications during DBE-based procedures were bleeding (1.1%), perforation (2.3%) and pancreatitis (2.3%), and minor complications occurred in up to 19.1%. CONCLUSION: The appropriate use of DBE yields a high rate of luminal access to papilla or enteral anastomoses in more than two-thirds of post-surgical patients, allowing important successful endoscopic therapeutic interventions.

e15585 Background: Due to the positive experience with combined AIO plus irinotecan (iri.) in a phase II trial (Möhler M et al, Br J Cancer 2005), this combination has been applied as first-line treatment in our department since 1999. Methods: 76 chemonaive patients (pts.) with histologically proven metastatic adenocarcinomas of the stomach or AEG tumours (tum.) (UICC IV), deemed to be non-resectable by the Interdisciplinary Tumour Board (ITB), were enrolled from 08/99 to 12/08. Chemotherapy (chemoth.) schedule: iri. (80 mg/m2 i.v. as 1h-infusion (inf.); d1, 8, 15, 22, 29, 36, qd 57) followed by 5-FU (2000 mg/m2 i.v.) with sodium folinic acid (500 mg/m2; d1, 8, 15, 22, 29, 36, qd 57) as 24h-inf. via port-a-cath. After downsizing the patients were again presented at the ITB. In 16 out of 76 pts. (21%) a secondary (sec.) metastatic resection (res.) with curative intent was taken into account. This collective is presented here evidencing the efficacy of this interdisciplinary procedure in palliative (pall.) treatment of gastric cancer. Results: Last date of evaluation: Dec/31/2008; median age: 58,7 years; men/women: n=12/4; res. of the primary tum. prior to pall. chemoth.: yes/no: n=2/14, ECOG 0/1: n=5/11; primary tum. localisation: AEG tum.: n=7; gastric carcinoma: n=9, elevated CEA yes/no: n=5/11, elevated CA19–9 yes/no: n=5/11. Number of metastatic localisations: 1/2/3: 69%/19%/12%, chemoth. application: total number:267; average value/patient:17 cycles altogether: 46, median cycles/pt.: 3, higher grade tox. (grade 3–4): anaemia 4%; diarrhea 2%, vomitus 2%, fever/infection 2%; response: PR 32%; SD 56 %; PD 6%; not evaluable 6 %; tum. control (PR, SD) 88 %; sec. res.: R0: 82 %; R1: 6 %, R2: 6 %; RX: 6%; gastrectomy with peritonectomy (R0): n=4 (25%), gastrectomy with lymph node dissection (D4,R0): n=6 (38%); HIPEC: n=4 (25%); 1-year survival:81%, 2-year survival: 44%, 3-year survival: 25%; deceased pts.: n=9 (56%), NED 19% (n=3). Conclusions: In our trial curative resections could be achieved in 82 % of the pts. During a follow-up of 20 months a NED status could be documented in 19% of the patients. No significant financial relationships to disclose.