VEGFR2 Signaling Prevents Colorectal Cancer Cell Senescence to Promote Tumorigenesis in Mice With Colitis.

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.

Bevacizumab plus chemotherapy as first-line treatment for patients with metastatic colorectal cancer: results from a large German community-based observational cohort study.

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.

Metastatic adenocarcinomas of the stomach or esophagogastric junction (UICC stage IV) are not always a palliative situation: a retrospective analysis.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Antiemetic prophylaxis and frequency of chemotherapy-induced nausea and vomiting in palliative first-line treatment of colorectal cancer patients: the Northern Bavarian IVOPAK I Project.

PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Palliative first-line therapy with weekly high-dose 5-fluorouracil and sodium folinic acid as a 24-hour infusion (AIO regimen) combined with weekly irinotecan in patients with metastatic adenocarcinoma of the stomach or esophagogastric junction followed by secondary metastatic resection after downsizing.

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).

Neoadjuvant treatment with weekly high-dose 5-fluorouracil as a 24h-infusion, folinic acid and biweekly oxaliplatin in patients with primary resectable liver metastases of colorectal cancer: long-term results of a phase II trial.

BACKGROUND: In 2003 Wein et al. published data after a short median follow up (23 months). Here we report on the long-term results. MATERIAL/METHODS: 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. RESULTS: 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%. CONCLUSIONS: 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.

Palliative first-line treatment with weekly high-dose 5-fluorouracil as 24h-infusion and gemcitabine in metastatic pancreatic cancer (UICC IV).

BACKGROUND: 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. MATERIAL/METHODS: 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. RESULTS: 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%. CONCLUSIONS: 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.

Weekly high-dose 5-fluorouracil as a 24-h infusion and sodium folinic acid (AIO regimen) plus irinotecan in patients with locally advanced nonresectable and metastatic adenocarcinoma or squamous cell carcinoma of the oesophagus: a phase II trial.

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.

Experiences with a long-term treatment of a massive gluteal acne inversa with infliximab in Crohn's disease.

BACKGROUND: 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. CASE REPORT: 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. CONCLUSIONS: 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.

Alterations in the tissue inhibitor of metalloproteinase-3 (TIMP-3) are found frequently in human colorectal tumours displaying either microsatellite stability (MSS) or instability (MSI).

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.

Antiphospholipid syndrome in combination with autoimmune hepatitis.

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.

Palliative treatment of colorectal cancer in Germany: cost of care and quality of life.

INTRODUCTION: 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. METHODS: 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. RESULTS: 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. DISCUSSION: 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.

Granulomatous lung disease requiring mechanical ventilation induced by a single application of oxaliplatin-based chemotherapy for colorectal cancer: a case report.

Combined chemotherapeutic regimens in conjunction with oxaliplatin are considered safe and effective treatment options in the clinical management of metastatic colorectal cancer. A 62-year-old male patient with a metastatic rectal carcinoma developed a pulmonary reaction after the first application of the combined standard chemotherapy regimen (5-fluorouracil and sodium folinic acid as a 24 h infusion and oxaliplatin). Following the first dose of chemotherapy, the patient developed acute dyspnoea and fever. A computerised scan of the chest revealed bilateral pulmonary patchy consolidation. Despite high-dose empiric antibiotic and antimycotic treatment, no clinical improvement was seen. The patient's condition deteriorated, and he required invasive mechanical ventilation. Diagnostic thoracoscopic wedge resections were performed for further diagnosis. The histological workup revealed distinct granulomatous inflammation, but no microbial pathogens were to be found. Thereupon, a drug-induced reaction to chemotherapy was suspected and high-dose steroid treatment initiated. Subsequently, the patient's respiratory condition improved and he was extubated. The present case exemplifies the rare course of a bilateral pneumonia-like, drug-induced granulomatous reaction following a single application of oxaliplatin. In addition to the known side effects of oxaliplatin-containing combination chemotherapy, unexpected serious adverse events in the form of pulmonary toxicities should also be taken into account.

Complete Long-Term Remission of an Inflammatory Pseudotumor under Corticosteroid Therapy.

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.

Double-balloon-enteroscopy-based endoscopic retrograde cholangiopancreatography in post-surgical patients.

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.

Long-Term Relapse-Free Survival by Interdisciplinary Collaboration in a Patient with Metastatic Pancreatic Cancer (UICC IV).

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/m(2) gemcitabine combined with 2,000 mg/m(2) 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.

Non-compliance in surveillance for patients with previous resection of large (> or = 1 cm) colorectal adenomas.

AIM: To assess the extent and reasons of non-compliance in surveillance for patients undergoing polypectomy of large (> or = 1 cm) colorectal adenomas. METHODS: Between 1995 and 2002, colorectal adenomas > or = 1 cm were diagnosed in 210 patients and subsequently documented at the Erlangen Registry of Colorectal Polyps. One hundred and fifty-eight patients (75.2%) could be contacted by telephone and agreed to be interviewed. Additionally, records were obtained from the treating physicians. RESULTS: Fifty-four out of 158 patients (34.2%) neglected any surveillance. Reasons for non-compliance included lack of knowledge concerning surveillance intervals (45.8%), no symptoms (29.2%), fear of examination (18.8%) or old age/severe illness (6.3%). In a multivariate analysis, the factors including female gender (P = 0.036) and age > 62 years (P = 0.016) proved to be significantly associated with non-compliance in surveillance. CONCLUSION: Efforts to increase compliance in surveillance are of utmost importance. This applies particularly to women's compliance. Effective strategies for avoiding metachronous colorectal adenoma and cancer should focus on both the improvement in awareness and knowledge of patients and information about physicians for surveillance.