To date, EGF 61*A/G, TGF-β1 -509*T/C and TNF-α -308*A/G gene polymorphisms have been not been analysed in pancreatic carcinoma. This study investigated the frequency of these gene polymorphisms among patients with cancer of the pancreatic head.A total of 73 pancreatic head cancer patients and 117 cancer-free healthy people were recruited at the Surgical Department of the University Hospital Mannheim. Genomic DNA was isolated from peripheral blood and gene polymorphisms were analysed by PCR-RFLP.The distribution of EGF 61*G/G homozygotes among pancreatic head cancer patients was more frequent than that in the control group (24.7% vs 11.1%, odds ratio (OR) = 2.618, 95% confidence interval (CI) = 1.195-5.738). In addition, the frequency of the G allele in the pancreatic head cancer patient group was also higher than that in the control group (45.9% vs. 33.3%, OR = 1.696, 95% CI = 1.110-2.592). No difference was found for the TGF-β1 -509 and TNF-α -308 genotypes among pancreatic head cancer patients and healthy controls.The frequencies of the EGF 61*G/G genotype and G allele are significantly increased among patients with pancreatic head cancer. TGF-β1-509*T/C and TNF-α -308*A/G gene polymorphisms are not related to this cancer entity.

To date, EGF 61*A/G, TGF-β1 -509*T/C and TNF-α -308*A/G gene polymorphisms have been not been analysed in pancreatic carcinoma. This study investigated the frequency of these gene polymorphisms among patients with cancer of the pancreatic head.A total of 73 pancreatic head cancer patients and 117 cancer-free healthy people were recruited at the Surgical Department of the University Hospital Mannheim. Genomic DNA was isolated from peripheral blood and gene polymorphisms were analysed by PCR-RFLP.The distribution of EGF 61*G/G homozygotes among pancreatic head cancer patients was more frequent than that in the control group (24.7% vs 11.1%, odds ratio (OR) = 2.618, 95% confidence interval (CI) = 1.195-5.738). In addition, the frequency of the G allele in the pancreatic head cancer patient group was also higher than that in the control group (45.9% vs. 33.3%, OR = 1.696, 95% CI = 1.110-2.592). No difference was found for the TGF-β1 -509 and TNF-α -308 genotypes among pancreatic head cancer patients and healthy controls.The frequencies of the EGF 61*G/G genotype and G allele are significantly increased among patients with pancreatic head cancer. TGF-β1-509*T/C and TNF-α -308*A/G gene polymorphisms are not related to this cancer entity.

Drug Prescribing for Patients with Chronic Kidney Disease in General Practice: a Cross-Sectional Study

OBJECTIVE To elucidate the association of TNF-alpha-308G/A gene functional polymorphism with the development and progression of colorectal cancer. METHODS PCR-RFLP was employed to detect the TNF-alpha-308 G/A genotypes in 157 colorectal cancer patients and 117 healthy controls. RESULTS The frequency of TNF-alpha-308 genotype and allele were not significantly different between colorectal cancer patients and healthy controls (genotype chi(2)=1.054, P=0.591, allele chi(2)=0.404, P=0.525). The frequency of A/A genotype and A allele in III+IV stage (62 patients in total) were higher than those in I+II stages (85 patients in total) (A allele: 22.6% vs 12.9%, A/A genotype: 8.1% vs 1.2%), and the differences were significant (genotype P=0.048, OR=7.368, 95% CI=0.839-64.743, allele chi(2)=4.720, P=0.03, OR=1.962, 95% CI=1.061-3.628). The frequency of TNF-alpha-308 genotype were not significantly different among different colorectal cancer grades (chi(2)=3.009,P=0.591). CONCLUSION TNF-alpha-308G/A gene polymorphism is not associated with the development of colorectal cancer, but TNF-alpha-308 A/A genotype and A allele are related to the progression of colorectal cancer.

Up to the present, EGF 61 A/G, TGF-β1 −509 T/C, and VEGF 936 T/C gene polymorphisms have been analyzed in other cancer entities than colorectal cancer. We have now investigated the frequency of these gene polymorphisms among colorectal cancer patients.

OBJECTIVETo investigate the association between VEGF gene 936 T/C polymorphism and colorectal cancer together with anastomotic leakage.METHODSPolymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to detect the VEGF 936 T/C genotypes in colorectal cancer patients and healthy controls.RESULTSThere was no significant difference in the frequency of VEGF 936 C/C genotype or C allele between colorectal cancer patients and healthy controls (P > 0.05). The C/C genotype or C allele in colorectal cancer patients with anastomotic leakage was less frequently found than in the group without anastomotic leakage (P < 0.05).CONCLUSIONSVEGF 936 C/C genotype or C allele is not related to the development of colorectal cancer, but they can reduce the risk of anastomotic leakage after surgery in colorectal cancer patients.

In tumor cells, high phosphorylation levels of receptor tyrosine kinases may occur in the absence of exogenous ligands due to autocrine signaling or enhanced tyrosine kinase activity. Here we show that the phosphorylation state of the endogenous epidermal growth factor receptor ( EGFR) can be quantitatively imaged in tumor cells and tissues by detecting fluorescence resonance energy transfer between fluorophores conjugated to antibodies against the receptor and phosphotyrosine, respectively. Five different human colorectal cell lines were analyzed for activity and expression of EGFR. All cell lines exhibited basal EGFR phosphorylation under serum starvation conditions. Phosphorylation levels increased after stimulation with EGF or pervanadate, dependent on the level of basal EGFR phosphorylation in the respective cell lines. This basal activity correlated inversely with receptor expression. Using the acceptor photobleaching fluorescence resonance energy transfer imaging approach, a significantly higher phosphorylation state of EGFR was also found in resected human colorectal tumor samples as compared with adjacent healthy tissue. Imaging of EGFR phosphorylation may thus serve as a valuable tool to investigate the role of receptor tyrosine kinase activity in malignant cell growth.

Optimizing medical donor management may have a considerable impact on transplantation outcome. This study investigated the effect of donor dopamine on initial graft function in renal allograft recipients, involving 254 consecutive recipients of a cadaver kidney, aged 18-74 years, transplanted between 1990 and 2003. Immunosuppression was based on cyclosporine. Patients were grouped according to donor use of dopamine during intensive care. Delayed graft function (DGF), and serial creatinine concentrations were compared between the groups. Dopamine-treated and -untreated donors were very similar regarding hemodynamics and renal function. Delayed graft function occurred in 47/158 treated and 48/96 untreated kidneys (p = 0.001). Donor dopamine was associated with a more rapid decrease of s-creatinine, which became obvious on the first postoperative day. Of patients in the treated and untreated group, respectively, 81.9% and 65.8% reached a s-creatinine level less than 2 mg/dL during the first month (p = 0.005). Donor dopamine remained predictive of a normalized s-creatinine level [HR 1.71; 95% CI 1.22-2.41] after controlling for confounding factors by multivariate Cox regression. Donor dopamine is associated with improvements of initial graft function after kidney transplantation. The beneficial effect of dopamine is achievable without side-effects for the recipients, and correlates with superior long-term graft survival.

Screening of patients at risk for hepatocellular carcinomas (HCC) and preventive virustatic therapy are the first steps in a multimodal treatment concept, because delayed detection leads to a poor prognosis with median survival of <10 months. Surgical resection of HCC is still the treatment of choice in patients with good residual liver function, however, recurrence-free 5-year survival after curative resection is low (33%). In patients with cirrhosis, only 25% of HCC are resectable, limited by low hepatic functional reserve. HCC in patients with non-cirrhotic livers are the domain of extended resections. In newer reports, transplantation in patients with cirrhosis is rated more positively when restricted to patients with solitary nodules <5 cm or up to 3 tumors <3 cm. A new option in HCC therapy are the local methods for tumor ablation, preferably radiofrequency ablation (RFA), especially in patients with limited liver function, non-resectable or multifocal tumors. A new horizon is opened combining these options and multimodal approaches with transarterial chemoembolisation (TACE). This trend to multimodal approaches promises a yet unknown improvement in the prognosis of patients with HCC. Controlled randomized studies comparing and validating the different methods and defining combined treatments according to liver function and tumor stage are eagerly awaited.

The expression of 14 individual and two groups of tumor antigens was characterized for colorectal carcinoma by RT-PCR using 26 colorectal carcinoma specimens, eight cell lines, six samples of patients with inflammatory bowl diseases, and nine specimens from different locations of an individual patient with a metastasized rectal carcinoma. The most frequently detected mRNAs were MAGE-A1 (58%), GAGE-3–7 (54%), and cTAGE-5a (31%). At medium frequencies (12–19%) we found cTAGE-1, MAGE-A2, se57-1, RAGE-4, and GAGE-1,2,8, while other tumor antigens were expressed rarely (<9%). 85% of the samples were positive for at least one of the most frequently expressed antigens. Using a secondary SEREX approach and sera of eight colorectal cancer patients we found reactive antibodies against recombinant cTAGE-1 (2 sera), se57-1 (2), truncated GAGE (1), and MAGE-A1 (1). We conclude that certain cancer-germline genes can be detected in colorectal cancer and might therefore be promising targets for immunotherapy.

OBJECTIVES:The cysteine proteases cathepsin B (CTSB) and L (CTSL) have been implicated in tumor spread and metastatic formation. In pancreatic adenocarcinoma, the role of these proteases is not very well defined. To find out which cell types produce CTSB and CTSL and to evaluate the prognostic impact of these proteases, 70 specimens from curatively resected patients with pancreatic adenocarcinoma were examined by in situ hybridization and immunohisto-chemistry.METHODS:Seventy patients with ductal adenocarcinoma of the pancreas were studied after R0 resection with a follow-up of at least 3 years. CTSB and CTSL expression was performed immunohisto-chemically using polyclonal anti-CTSB and CTSL antibodies. To detect cell types involved in producing CTSB and CTSL as well as the intracellular localization of specific mRNA sequences, nonisotopic in situ hybridization was performed. The correlations among CTSB and CTSL expression, clinicopathologic parameters, and clinical outcome were analyzed.RESULTS:The immunoreactivity was 96% for CTSB and 90% for CTSL. Positive mRNA signals were obtained in the cytoplasm tumor cells, macrophages, and fibroblasts in 77% for CTSB and 81% for CTSL, respectively. Statistical analysis showed a significant correlation between CTSB/CTSL expression and tumor grading (P < 0.05) and between CTSB and lymphatic invasion (P = 0.05). Kaplan-Meier analyses revealed statistical significance for CTSB/CTSL expression with the survival after curative resection (P < 0.05). Both proteases are strong prognostic markers in multivariate analysis (P = 0.0001) beside UICC stage, nodal status, tumor size, and grading (P < 0.05). Furthermore, CTSB expression is an independent prognostic marker for cancer recurrence within 6 months after curative surgery in multivariate analysis (P = 0.0001).CONCLUSIONS:CTSB and CTSL are strong and independent prognostic markers in resectable pancreatic adenocarcinoma rather than UICC stage, TNM classification, or tumor grading. Furthermore, CTSB is a predictor for early recurrence after curative resection. These data underline the significance of tumor-associated proteolysis for cancer invasion and metastasis and may lead to defining subgroups of patients with early recurrence and poor outcome.

The prognosis of patients who undergo resection for pancreatic ductal adenocarcinoma with curative intention is generally poor unless they have early-stage disease. Based on our 25-year experience, the results of 194 patients after a standardized Kausch-Whipple resection for adenocarcinoma of the pancreatic head were analyzed and the prognostic factors were evaluated. Between 1972 and 1998 a total of 221 patients were diagnosed for ductal adenocarcinoma of the pancreatic head, and 194 of them subsequently underwent a standardized Kausch-Whipple resection. Long-term results and prognostic factors were examined by multivariate and univariate analyses. The overall postoperative mortality was 3.09%, and the morbidity was 29.9%. By multivariate analysis only curative resection (R0) was significantly related to a favorable prognosis ( p < 0.0001). Furthermore, in case of a curative resection, the presence of lymph node metastases showed prognostic significance in the multivariate analysis ( p = 0.005). Cumulative survival analysis revealed a 5-year survival rate of 25.4%, a 7-year survival rate of 12.3%, and a 10-year survival rate of 8.2% for patients who underwent curative resection (R0) for adenocarcinoma of the pancreatic head. We demonstrated that the R0 status is the only independent prognostic factor after surgery for adenocarcinoma of the pancreatic head. In the case of a curative resection, the presence of lymph node metastases is of prognostic relevance. In view of considerable surgical morbidity and mortality, resection for cancer of the pancreatic head is the only option if the lesion is resectable. We concluded that surgical treatment is “as good as it gets,” as extended techniques have not proved to produce better results.

In the obstructed gut, nitric oxide (NO) may influence intestinal barrier function and translocation of bacteria. By using a novel experimental approach, we investigated the effect of supplementation and inhibition of NO synthesis on the time interval necessary for translocation of green fluorescent protein-transfected Escherichia coli (GFP-uv E. coli) in a rat model of small bowel obstruction. In anesthetized Wistar rats, 4 x 10(8) GFP-uv E. coli were administered into a reservoir of terminal ileum formed by ligature. Animals were randomized to receive either i.v. arginine (10 mg/kg), aminoguanidine (300 mg/kg), L-NAME (25 mg/kg), or saline (control). Translocation of GFP-uv E. coli was assessed using intravital video microscopy. Minimal transit time of translocation was measured as time from injection of GFP-uv E. coli into the gut lumen until bacteria were observed in the lamina submucosa and as time from injection of bacteria into the gut lumen until bacteria were observed in the lamina muscularis propria. Minimal transit times were expressed as mean +/- SD. Bacterial translocation into the submucosa and muscularis propria took 36 +/- 7 min and 81 +/- 9 min, respectively in control animals receiving saline. Aminoguanidine and L-NAME caused a marked delay of minimal transit time into the submucosa (63 +/- 5 min and 61 +/- 7 min, respectively; P < 0.05). Arginine significantly accelerated bacterial translocation into the muscularis propria (61 +/- 9 min, P < 0.05). GFP-uv E. coli were detected on frozen sections of small bowel, mesentery, liver, and spleen 2 h after GFP-uv E. coli administration in all animals. A marked upregulation of inducible NO synthase (NOS) in the obstructed bowel segment was demonstrated on immunohistochemistry. The assessment of a newly defined parameter, minimal bacterial transit time, may serve as an additional functional aspect of intestinal barrier function for pathophysiological and pharmacological studies. Aminoguanidine, L-NAME, and arginine were effective in influencing minimal transit time of E. coli during small bowel obstruction.

Background: Vomiting, aspiration, flatulence, and diarrhea are well-known negative side effects of enteral nutrition through percutaneous endoscopic gastrostomy (PEG). However, it is not yet clarified if pump-assisted (PA) or gravity-controlled (GC) application is the more comfortable and safe choice for long-term nutrition through PEG. Methods: This was a prospective, randomized, crossover study. Fifty long-term PEG patients were fed by PA nutrition (G1) and 50 patients were fed by GC nutrition (G2). Six weeks of observation (O1) was followed by a switch of method of nutritional application in both groups and an additional 6 weeks of observation (O2). Daily determination of comfort and safety was done with a standardized questionnaire. Evaluation of blood glucose levels on days 1, 21, and 42 during O1 and O2. Results: The patients in both groups had the same medical conditions and were of the same age and sex. Far less flatulence (p < .0006) and epigastric fullness (p < .0003) was discovered in G1 during O1. Also, significantly less regurgitation (p < .0002) and vomiting of feeding diet (p < .0001) in G1 versus G2 could be observed. The rate of diarrhea (p < .0003) in G2 was higher than in G1. The daily profile of blood glucose was significantly better (p < .0008) in G1 than in G2. After the nutritional application was changed in O2, the PA group (G2) again showed a significantly better rate of flatulence, epigastric fullness, regurgitation, vomiting, diarrhea, and daily profile of blood glucose. Ninety-six percent of the patients in G2 preferred further nutrition by PA after finishing this study. All patients in G1 continued their accustomed nutrition by PA. Conclusion: Nutrition through PA showed not only a higher comfort rate but also increased safety, which was expressed through a low rate of regurgitation and vomiting. PA presented better glucose metabolization manifested in improved blood glucose levels. As a result of this prospective study, PA is preferable to GC and preferred by patients with long-term PEG nutrition.

We report a case of sudden death after gas gangrene. A 67-year-old male patient with diabetes mellitus and chronic renal failure (on haemodialysis three times a week) presented in the surgical emergency department with a severe swelling and crepitation in the right groin. No signs of trauma were present-except for a well-healed, 1-year-old scar after femoro-popliteal bypass surgery. Two days earlier, he had presented to the internal medicine department with epigastric pain and had left against medical advice. On readmission the patient was initially conscious and in a stable cardiopulmonary condition but developed sudden cardiocirculatory failure and underwent resuscitation. Despite all resuscitation measures, including the administration of high doses of catecholamines and the treatment of hyperkalemia, the patient died. Autopsy revealed septicaemia with rod-shaped gram-positive bacteria, typical of Clostridium perfringens, evidenced by multiple areas of myonecrosis. Abscess formation was found in the myocardium. Clostridial gas gangrene is a rare clinical condition. Unless immediate diagnosis and adequate therapy measures are taken, the outcome and chances for survival are poor as demonstrated by this case.

Many animal models for metastatic colorectal cancer represent clinical manifestations just inaccurately. We introduce a novel mouse model for metastastatic colorectal cancer. In order to remain close to the clinical disease a syngenic murine colon carcinoma cell line (colon 26 cells) was transfected with enhanced green fluorescent protein (EGFP). The transfected cells maintain the highly malignant attributes of the wild-type cells. Following injection into the portal circulation of Balb/c-mice, liver metastases occur in the same time span. Using the fluorescent attributes of the transfected cells, an approximation of the tumor load in liver tissue can be achieved by fluorescence activated cell sorting (FACS) and fluoroscan analysis. Tumor cell load in liver tissue can be accurately measured by Northern blot and Western blot analysis of liver tissue containing EGFP-transfected colon cancer metastases (1250 cells/mg liver tissue and 1000 cells/mg liver tissue) respectively. Confocal microscopy and intravital microscopy confirmed the growth of tumor metastases, originating from the intravascular compartments. The presented animal model using EGFP-transfected colon 26 cells allows the detecting of tumor growth in vivo and post mortem, as well as an accurate quantification of the tumor load in the liver tissue.