Search

Hintergrund: Verschiedene Faktoren der Lebensführung spielen eine zentrale Rolle in der Primär- und Tertiärprävention des kolorektalen Karzinoms (CRC). Das Ziel dieser Übersichtsarbeit ist es, die Datenlage zu den Auswirkungen der Lifestyle-Faktoren körperliche Aktivität (KA) und Ernährung in der Primär- und insbesondere der Tertiärprävention des CRC zusammenzufassen. Methoden: Mit Blick auf den Einfluss der Lifestyle-Faktoren auf die Prognose und die Lebensqualität (LQ) der Patienten wurde eine umfassende Literaturrecherche in Publikationen zu klinischen Studien vor allem aus den Jahren 2000 bis 2015 durchgeführt und der aktuelle Wissensstand auf der Grundlage dieser klinischen Studien zusammengefasst. Ergebnisse: Neben der Vermeidung von Risikofaktoren (wie Rauchen und übermäßiger Alkoholgenuss) können ein gesundes Körpergewicht, regelmäßige und moderate KA sowie eine mediterrane Ernährung mit viel Obst, Gemüse, Geflügel und Fisch das Erkrankungsrisiko signifikant verringern. Patienten mit bereits diagnostiziertem CRC können auch aktiv ihre CRC-Prognose und ihre LQ verbessern, indem sie ihre Lebensgewohnheiten umstellen. Patienten, die ein moderates Trainingsprogramm aufnehmen und ihre Essgewohnheiten im Sinne der mediterranen Ernährung ändern, können die krebsspezifische und die Gesamtmortalität um bis zu 40% senken und schon während der Chemotherapie ihre LQ signifikant erhöhen. Daher sollten Ärzte, die CRC-Patienten behandeln, diesen Patienten moderate KA, Kalorienrestriktion und ein mediterranes Ernährungsmuster empfehlen. Die systematische Literaturrecherche des World Cancer Research Fund/American Institute for Cancer Research (AICR/WCRF) von 2007 zeigt zudem, dass nach der Diagnosestellung dieselben Empfehlungen zur Lebensführung gelten wie für die Prävention der Krankheit. Schlussfolgerung: Faktoren der Lebensführung wie moderate KA und mediterrane Ernährung verbessern die LQ und die Prognose von Patienten mit CRC. Die Erkenntnisse zur Wirkung der Umstellung von Lebensgewohnheiten beruhen jedoch hauptsächlich auf Beobachtungsstudien; es gibt nur wenige prospektive Studien und keine randomisierten. Daher rechtfertigen die Beobachtungsstudien kontrollierte randomisierte Studien, die die Wirkung einer solchen Umstellung auf LQ und Krebsrezidivierung nachweisen. Übersetzung aus Visc Med 2016;32:199-204 (DOI:10.1159/000446492)

Background: Lifestyle factors play a pivotal role in the primary and tertiary prevention of colorectal cancer. The purpose of this review article is to summarize data concerning the effect of the lifestyle factors physical activity (PA) and nutrition in primary and, more importantly, tertiary prevention of colorectal cancer (CRC). Methods: Focusing on the influence of lifestyle factors on prognosis und quality of life (QOL), a comprehensive literature search of clinical studies published mainly in the years 2000 until 2015 was performed and the current knowledge based on these clinical studies reviewed. Results: Besides avoiding risk factors (such as smoking and overindulgence in alcohol), healthy weight, regular and moderate PA as well as a diet which contains fruit, vegetables, poultry, and fish (so-called ‘Mediterranean' diet) may reduce the risk of the disease significantly. Patients already diagnosed with CRC can also actively improve the prognosis of CRC and QOL by changing their lifestyle. Patients commencing moderate exercise and modifying their eating habits in terms of a ‘Mediterranean' diet can reduce cancer-specific and overall mortality by up to 40% and significantly increase their quality of life already during chemotherapy. Therefore, moderate physical exercise, calorie restriction, and a Mediterranean dietary pattern for patients with CRC should be recommended by physicians treating these patients. In fact, the World Cancer Research Fund/American Institute for Cancer Research (AICR/WCRF) systematic literature review from 2007 shows that the lifestyle changes recommended after diagnosis are the same for primary prevention of this disease. Conclusion: Lifestyle changes such as moderate PA and a Mediterranean diet significantly improve the QOL as well as the prognosis of patients suffering from colorectal disease. However, the effect of lifestyle changes is mostly based on observational studies, while only few studies are prospective and none are randomized. Therefore, these observational studies warrant controlled randomized trials to prove the effectiveness of lifestyle interventions on QOL and cancer recurrence.

Summary Background There is substantial uncertainty regarding the optimal surgical treatment for chronic pancreatitis. Short-term outcomes have been found to be better after duodenum-preserving pancreatic head resection (DPPHR) than after partial pancreatoduodenectomy. Therefore, we designed the multicentre ChroPac trial to investigate the long-term outcomes of patients with chronic pancreatitis within 24 months after surgery. Methods This randomised, controlled, double-blind, parallel-group, superiority trial was done in 18 hospitals across Europe. Patients with chronic pancreatitis who were planned for elective surgical treatment were randomly assigned to DPPHR or partial pancreatoduodenectomy with a central web-based randomisation tool. The primary endpoint was mean quality of life within 24 months after surgery, measured with the physical functioning scale of the European Organisation for Research and Treatment of Cancer QLQ-C30 questionnaire. Primary analysis included all patients who underwent one of the assigned procedures; safety analysis included all patients who underwent surgical intervention (categorised into groups as treated). Patients and outcome assessors were masked to group assignment. The trial was registered, ISRCTN38973832. Recruitment was completed on Sept 3, 2013. Findings Between Sept 10, 2009, and Sept 3, 2013, 250 patients were randomly assigned to DPPHR (n=125) or partial pancreatoduodenectomy (n=125), of whom 226 patients (115 in the DPPHR group and 111 in the partial pancreatoduodenectomy group) were analysed. No difference in quality of life was seen between the groups within 24 months after surgery (75·3 [SD 16·4] for partial pancreatoduodenectomy vs 73·0 [16·4] for DPPHR; mean difference −2·3, 95% CI −6·6 to 2·0; p=0·284). The incidence and severity of serious adverse events did not differ between the groups. 70 (64%) of 109 patients in the DPPHR group and 61 (52%) of 117 patients in the partial pancreatoduodenectomy group had at least one serious adverse event, with the most common being reoperations (for reasons other than chronic pancreatitis), gastrointestinal problems, and other surgical morbidity. Interpretation No differences in quality of life after surgery for chronic pancreatitis were seen between the interventions. Results from single-centre trials showing superiority for DPPHR were not confirmed in the multicentre setting. Funding German Research Foundation (DFG).

To find out whether wide local resection is adequate treatment for patients with benign tumours of the papilla of Vater.Retrospective study.University hospital, Germany.31 patients with benign tumours out of a total of 129 with lesions of the ampulla of Vater treated between May 1978 and February 1995.Histological examination of specimens before, during, and after the operation.Sensitivity and positive predictive value of histological examination, and outcome of treatment.Histological examination before and during the operation had a sensitivity of 89% and 97%, respectively. 28 patients were treated by wide excision of the ampulla and 3 by pylorus-preserving partial pancreaticoduodenectomy. At a median follow up of 43 months (range 6-156) there was no evidence of recurrent disease.Wide excision of the ampulla with reconstruction and reimplantation of the duct is adequate treatment for benign lesions. If the histological picture is uncertain, partial pancreaticoduodenectomy is justified in patients at low risk.

Oxidative stress is an important factor in the pathogenesis of acute pancreatitis, as shown in vivo by the beneficial effects of scavenger treatment and in vitro by the potential of free radicals to induce acinar cell damage. However, it is still unclear whether oxygen free radicals (OFR) act only as mediators of tissue damage or represent the initiating event in acute pancreatitis in vivo as well. In the present study the authors aimed to address this issue in an experimental set-up.Two hundred male Wistar rats were randomly assigned to one of the following experimental groups. In two groups, acute necrotizing pancreatitis was induced by retrograde intraductal infusion of 3% sodium taurocholate. Through the abdominal aorta, a catheter was advanced to the origin of the celiac artery for continuous regional arterial (CRA) pretreatment with isotonic saline (NP-S group) or superoxide dismutase/catalase (NP-SOD/CAT group). In another group, oxidative stress was generated by CRA administration of xanthine oxidase and intravenous administration of hypoxanthine (HX/XOD group). Sham-operated rats received isotonic saline both arterially and intraductally. After observation periods of 5 and 30 minutes and 3 and 6 hours, the pancreas was removed for light microscopy and determination of reduced glutathione (GSH), oxidized glutathione (GSSG), conjugated dienes (CD), and malondialdehyde as a marker for OFR-induced lipid peroxidation as well as myeloperoxidase as a parameter for polymorphonuclear leukocyte accumulation.A significant decrease of GSH was paralleled by an increased ratio of GSSG per total glutathione and elevated CD levels after 5 minutes in the NP-S group versus the sham-operated group. Thereafter, the percentage of GSSG and GSH returned to normal levels until the 6-hour time point. After a temporary decrease after 30 minutes, CD levels increased again at 3 hours and were significantly higher at 6 hours in contrast to sham-operated rats. Myeloperoxidase levels were significantly elevated at 3 and 6 hours after pancreatitis induction. In contrast to NP-S rats, treatment with SOD/CAT significantly attenuated the changes in glutathione metabolism within the first 30 minutes and the increase of CDs after 6 hours. HX/XOD administration lead to changes in levels of GSH, GSSG, and CDs at 5 minutes as well as to increased myeloperoxidase levels at 3 hours; these changes were similar to those observed in NP-S rats. Acinar cell damage including necrosis was present after 5 minutes in both NP groups, but did not develop in HX/XOD rats. In addition, serum amylase and lipase levels did not increase in the latter group. SOD/CAT treatment significantly attenuated acinar cell damage and inflammatory infiltrate compared with NP-S animals during the later time intervals.OFRs are important mediators of tissue damage. However, extracellular OFR generation alone does not induce the typical enzymatic and morphologic changes of acute pancreatitis. Factors other than OFRs must be involved for triggering acute pancreatitis in vivo.

Using a retrograde infusion sodium taurocholate pancreatitis model in the rat treatment with oxygen radical scavengers or monoclonal anti-ICAM-1 antibody decreased tissue damage and polymorphonuclear leukocytes (PMN) infiltration. Scavengers or anti-ICAM-1 treatment attenuated the activating capacity of blood PMNs following zymosan stimulation. The local production of oxygen free radicals in the pancreas by systemic infusion of hypoxanthine and regional infusion of xanthine oxidase did not induce acute pancreatitis, although an increase of infiltrating PMNs was observed. Our data suggest that oxygen free radicals and infiltrating PMNs aggravate acute pancreatitis and that both are important mediators of local destruction and systemic activation of PMNs.

We investigated the effects of endogenously produced and exogenously applied nitric oxide (NO) on cell proliferation rates and cell cycle regulation in senescent human fibroblasts (WI38). Induction of inducible nitric oxide synthase by tumor necrosis factor-alpha, interferon-gamma and interleukin-1beta inhibited cell proliferation and led to a G1 arrest. These effects were partially reversible by N(G)-monomethyl-arginine (NMA). Addition of the NO donors sodium nitroprusside (SNP) or S-nitroso-N-acetylpenicillamine (SNAP) increased cell proliferation rates as well as the S/G2 fraction. This points to a functional role of NO in cell cycle regulation and cell proliferation in human fibroblasts which depends on the mode of NO generation as well as the culture conditions used.

Background/Aim : In spite of the interest in free radicals as mediators of ischemic damage, most information on these species in biological systems is derived from indirect measurements. Our aim was to obtain more direct information concerning sources of free radical production during ischemia and reperfusion. Methods : We have performed simultaneous measurement of radical generation, purine metabolites, reduced glutathione, neutrophil infiltration and morphological appearance in the cat small intestine in vivo during 60 minutes of ischemia followed by 60 minutes of reperfusion. Results : Radical formation increased abruptly on reperfusion and remained elevated in untreated animals. Inhibition by a monoclonal antibody (IB4) against the neutrophil and by allopurinol treatment was paralleled by improvement of biochemical and morphological parameters. The radicals detected during reperfusion could be divided into one component arising directly from the neutrophils, one due to the xanthine oxidase reaction, and one unknown source. Conclusions : Neutrophils are a major source of radical production during reperfusion after ischemia. Radicals formed in the xanthine oxidase reaction seem to function as a primer for the neutrophils. The nonsignificant linear correlation between radical formation and morphological appearance suggests that factors other than free radicals are important for the development of intestinal damage after a period of ischemia.

SUMMARY Background: After pancreatic surgery, some patients have complica tions that require treatment. Method: Review article based on a selective literature search and the German S3 guideline on pancreatic carcinoma. Results: Detailed knowledge of the surgical procedure and its potential early and late complications is a prerequisite for the recognition and treatment of problems occurring after pancreatic surgery. These may be due either to the operation itself or to the progression of the underlying pancreatic disease. Both diabetes mellitus and exocrine insufficiency are common long-term sequelae. If persistent pain should arise, its cause must be identified and treated. To prevent malnutrition and vitamin deficiency after pancreatic resection, patients should be given a diet with an increased fat content and with supplemental enzymes.

SUMMARY Summary Background: Colorectal carcinoma is the most common type of tumor in Western countries. The risk of developing colorectal carcinoma depends both on genetic factors (familial predisposition) and on lifestyle-related factors such as body-mass index, level of physical activity, and nutritional behavior. Regular physical activity is important in primary prevention, and there is also evidence that the prognosis after treatment of a colorectal carcinoma can be improved by exercise. Methods: The PubMed database was searched for relevant articles that appeared in the last 10 years, and selected articles were evaluated. Results: Cross-sectional studies have shown that regular physical activity (ca. 7 hours of brisk walking per week) lowers the risk of colon carcinoma by 40%. Physical activity also improves the outcome of patients already diagnosed with colorectal carcinoma: for example, patients with advanced disease (UICC stage II or III) have been found to survive significantly longer if they perform 4 hours of brisk walking per week, or the equivalent degree of physical exercise. Conclusions: Cross-sectional studies show that physically active persons are less likely to develop colorectal carcinoma than physically inactive persons, and that they have better outcomes in the event that they do develop the disease. The positive findings with respect to secondary prevention still need to be confirmed in interventional trials, but in primary prevention, at least, physical activity should be actively promoted, along with other beneficial lifestyle habits and screening measures.

The purpose of this study was to assess the involvement of oxygen radicals in acute edematous and hemorrhagic panreatitis. Acute pancreatitis was induced in rats by the CCK-analogue cerulein (5 μg/kg/h) and by retrograde injection of 5% sodium taurocholate for 30 min, 3.5 h, and 12 h. At the end of the infusion and observation time, serum enzymes, conjugated dienes, and malondialdehyde in the tissue were measured. Moreover, the tissue samples underwent light microscopical examination. In cerulein pancreatitis, an interstitial edema and intravascular margination of granulocytes in the pancreatic gland were observed after 3.5 h. After 12 h, the histological evaluation revealed a pronounced zymogen degranulation, extensive tissue necrosis and migration of granulocytes into the tissue. Parallelly, amylase and lipase increased by 15 and 35 times, respectively. In contrast, conjugated dienes and malondialdehyde increased in cerulein pancreatitis and reached their highest level after 3.5 h and decreased to normal levels after 12 h. The development of the histological damages and serum enzyme levels with sodium taurocholate pancreatitis was similar as compared to the cerulein pancreatitis, however, the development was faster and more traumatic. Already after 3.5 h an extensive zymogen degranulation and cell necrosis was observed. Concomitantly, the amylase and lipase levels increased by 90 and 30 times, respectively. Treatment with superoxide dismutase (100000 U/kg/h) and catalase (400 000 U/kg/h) prevented lipid peroxidation and reduced zymogen degranulation and tissue necrosis. Tissue edema and inflammatory response were not affected in both models of acute pancreatitis. Moreover, scavenger treatment improved the survival rate in sodium taurocholate pancreatitis. It is therefore concluded that oxygen free radicals seem to be instrumental for the development of the disease. Scavenger treatment can mitigate the pancreatic tissue damages and the extrapancreatic complications.

Background & Aims Pancreatic cancers contain exclusively tumorigenic cancer stem cells (CSCs), which are highly resistant to chemotherapy, resulting in a relative increase in CSC numbers during gemcitabine treatment. Signaling through sonic hedgehog and mammalian target of rapamycin (mTOR), respectively, may be essential for CSC self-renewal and could represent putative targets for novel treatment modalities. Methods We used in vitro and in vivo models of pancreatic cancer to examine the effects of sonic hedgehog inhibition (cyclopamine/CUR199691) and mTOR blockade (rapamycin) on the tumorigenic CSC population. Results Surprisingly, neither cyclopamine nor rapamycin alone or as supplements to chemotherapy were capable of effectively diminishing the CSC pool. Only the combined inhibition of both pathways together with chemotherapy reduced the number of CSCs to virtually undetectable levels in vitro and in vivo. Most importantly, in vivo administration of this triple combination in mice with established patient-derived pancreatic tumors was reasonably tolerated and translated into significantly prolonged long-term survival. Conclusions The combined blockade of sonic hedgehog and mTOR signaling together with standard chemotherapy is capable of eliminating pancreatic CSCs. Further preclinical investigation of this promising approach may lead to the development of a novel therapeutic strategy to improve the devastating prognosis of patients with pancreatic cancer.

Objective: The authors performed a prospective evaluation of staging laparoscopy with laparoscopic ultrasonography in predicting surgical resectability in patients with carcinomas of the pancreatic head and periampullary region.Summary Background Data: Pancreatic resection with curative intent is possible in a select minority of patients who have carcinomas of the pancreatic head and periampullary region. Patient selection is important to plan appropriate therapy and avoid unnecessary laparotomy in patients with unresectable disease. Laparoscopic ultrasonography is a novel technique that combines the proven benefits of staging laparoscopy with high resolution intraoperative ultrasound of the liver and pancreas, but which has yet to be evaluated critically in the staging of pancreatic malignancy.Methods: A cohort of 40 consecutive patients referred to a tertiary referral center and with a diagnosis of potentially resectable pancreatic or periampullary cancer underwent staging laparoscopy with laparoscopic ultrasonography. The diagnostic accuracy of staging laparoscopy alone and in conjunction with laparoscopic ultrasonography was evaluated in predicting tumor resectability (absence of peritoneal or liver metastases; absence of malignant regional lymphadenopathy; tumor confined to pancreatic head or periampullary region).Results: “Occult” metastatic lesions were demonstrated by staging laparoscopy in 14 patients (35%). Laparoscopic ultrasonography demonstrated factors confirming unresectable tumor in 23 patients (59%), provided staging information in addition to that of laparoscopy alone in 20 patients (53%), and changed the decision regarding tumor resectability in 10 patients (25%). Staging laparoscopy with laparoscopic ultrasonography was more specific and accurate in predicting tumor resectability than laparoscopy alone (88% and 89% versus 50% and 65%, respectively).Conclusions: Staging laparoscopy is indispensable in the detection of “occult” intraabdominal metastases. Laparoscopic ultrasonography improves the accuracy of laparoscopic staging in patients with potentially resectable pancreatic and periampullary carcinomas.

Background Carcinoma located in the uncinate process (CUP) of the pancreatic head is considered to be rare. Exact epidemiological data, however, are not available because the series published so far consist of fewer than ten patients. The purpose of this prospective study was to evaluate the clinical appearance of CUP and to compare findings with those of patients with carcinoma in the ventral aspect of the pancreatic head (VPC), which represents the most frequent localization. Results Some 39 (8 per cent) of 506 evaluated patients suffered from CUP. Mean age was 63·3 years. The most frequent complaints were upper abdominal pain (n = 32) and weight loss (n = 35). Jaundice was seen in only five patients and was never an early symptom. The level of CA19-9 was raised in 33 patients. The best diagnostic procedure to detect CUP was computed tomography (CT) (sensitivity 93 per cent), whereas endoscopic retrograde cholangiopancreatography was not useful (sensitivity 21 per cent). Vascular involvement was significantly (P < 0·01) more common in CUP (n = 19) than in VPC (48 versus 19 per cent). This finding and the fact that most patients with CUP were diagnosed at a late stage with distant metastasis or severe vascular involvement present (n = 21) are responsible for the significantly lower rate of operation (n = 25) (64 versus 92 per cent, P < 0·05) and the significantly shorter median survival time (5 versus 11 months, P < 0·05). Conclusion Patients with CUP have a poor prognosis as a result of the lack of early symptoms (jaundice) and early vascular involvement due to the proximity of the uncinate process to the mesenteric root. A raised level of CA19-9, together with weight loss and/or upper abdominal pain, should prompt CT.

Haemorrhagic mucosal lesions are produced during intestinal ischaemia and after reperfusion probably mediated by oxygen radicals. Oxygen radicals react with cell membrane lipids and induce cell damage by peroxidation and induce accumulation of polymorphonuclear leucocytes in the tissue. The aim of the study was to elucidate the involvement of polymorphonuclear leucocytes in post-ischaemic intestinal damage. Intestinal ischaemia was induced in cats by partial occlusion of the superior mesenteric artery. Samples from the small intestine were excised before and at the end of the two hour hypotensive period as well as 10 minutes and 60 minutes after reperfusion. Conjugated dienes, myeloperoxidase, and the purine metabolites were determined in the samples. The tissue was also examined histologically. Seven cats were treated before reperfusion with a monoclonal antibody (IB4) which inhibits leucocyte adherence to endothelial cells and its subsequent activation. After reperfusion myeloperoxidase activity increased and the ischaemic mucosal lesions worsened significantly. IB4 treatment prevented an increase in post-hypotensive myeloperoxidase activity and attenuated the normally observed severe mucosal lesions. We conclude that the severe post-ischaemic lesions are induced by polymorphonuclear leucocytes. Such mucosal injury may be appreciably reduced by blocking leucocyte adherence with IB4.

This study aimed to assess the role of oxygen free radicals in acute pancreatitis. Acute pancreatitis was induced in rats by infusion of the CCK-analogue cerulein (5 micrograms/kg per hour) for 30 minutes, 3.5 hours, and 12 hours. After the infusion, serum enzymes and conjugated tissue dienes and malondialdehyde were measured and tissue samples were subjected to electron and light microscopy. Electron microscopy after 30 minutes showed moderate intracellular alterations. After 3.5 hours of cerulein infusion interstitial oedema and intravascular margination of granulocytes in the pancreatic gland were seen. After 12 hours histological evaluation showed pronounced zymogen degranulation, extensive tissue necrosis, and migration of granulocytes into the tissue. Amylase and lipase activities increased 15 and 35-fold respectively during this time. After 30 minutes of cerulein infusion conjugated dienes and malondialdehyde increased, they reached their peak after 3.5 hours and decreased to normal values after 12 hours. Treatment with superoxide dismutase (100,000 U/kg/hour) and catalase (400,000 U/kg/hour) either before or after the start of the cerulein infusion prevented lipid peroxidation and reduced zymogen degranulation and tissue necrosis. Tissue oedema and inflammatory response, however, were not affected in any of the treated rats. Oxygen free radicals are instrumental in the development of acute pancreatitis. Even after its onset, scavenger treatment reduced the tissue damage normally observed.

The role of reactive oxygen species (ROS) generated by hypoxanthine/xanthine oxidase (HX/XO) in the induction of apoptosis was studied in the human fibroblast cell line WI38. Apoptosis but not necrosis was observed in proliferating fibroblasts after 48 h incubation with 1 mM HX and 0.05 U/ml XO. Induction of apoptosis was hindered by catalase. Cell-cycle analysis revealed a reduction of cells in the S/G2 phase 24 and 48 h after stimulation, suggesting that ROS induce a G1 arrest in proliferating fibroblasts. This was supported by an accumulation of p53 and the cdk inhibitor p21WAF1/CIP1. Since apoptosis was not inducible in senescent fibroblasts our data indicate that ROS mainly induces apoptosis in proliferating cells. © 1997 Federation of European Biochemical Societies.

Darmschaden nach Hypoxie scheinen durch freie Sauerstoffradikale verursacht zu sein. Der Darm von 20 Katzen wurde einer 2stundigen Ischamie unterworfen und dann reperfundiert. 7 Katzen bekamen vor Reperfusion Superoxiddismutase (SOD). Die schwersten Darmschaden wurden erst nach Reperfusion beobachtet. SOD scheint diese Schaden zu verhindern, da histologisch der Darm der behandelten Tiere nahezu intakt ist.