Enhanced ENA-78 and IL-8 expression in patients with malignant pancreatic diseases.

BACKGROUND/AIM: Pancreatic cancer is characterized by perineural invasion, early lymph node and liver metastases, and an extremely dismal prognosis. In the present study we aimed at investigating the expression profile of pro-inflammatory and angiogenic CXC chemokines as potential factors contributing to the aggressive biology of this gastrointestinal malignancy. METHODS: Protein expression profiles of the CXC chemokines growth-related oncogene alpha (GRO-alpha/CXCL1), epithelial cell-derived neutrophil-activating peptide-78 (ENA-78/CXCL5), granulocyte chemoattractant protein-2 (GCP-2/CXCL6), neutrophil-activating protein-2 (NAP-2/CXCL7), and interleukin-8 (IL-8/CXCL8) were assessed by enzyme-linked immunosorbent assay in pancreatic carcinoma, cancer of the papilla of Vater, pancreatic cystadenoma, and chronic pancreatitis specimens. RESULTS: IL-8 and ENA-78 protein expression was most pronounced in pancreatic carcinoma specimens, showing an 11-fold and 17-fold overexpression in comparison with non-affected neighbouring tissues, a 66-fold and 24-fold upregulation compared to pancreatic cystadenoma, and a 6-fold and 9-fold overexpression with respect to chronic pancreatitis, respectively (p < 0.05 between all groups). In addition, a close correlation between IL-8 and ENA-78 protein expression and advanced pancreatic carcinomas in relation to the T category was evident (p < 0.05). CONCLUSION: Our results demonstrate that ELR+ CXC chemokines are differentially expressed in malignant and non-malignant human pancreatic specimens, suggesting a potential contribution of these chemokines to the pathogenesis of pancreatic carcinoma.

Increased growth factor expression after hepatic and pancreatic resection.

Removal of the primary tumour is suggested to associate with an enhanced tumour growth of residual micrometastases. Recent data focus on growth factors that may be released in response to surgery-stimulating receptors of residual tumour cells. Vascular endothelial (VEGF) and hepatocyte growth factor (HGF) are potent inducers of angiogenesis. The two factors are necessary for wound healing and the promotion of tumour growth. This study was designed to determine growth factor serum levels in patients before, during and after major abdominal surgery. It was recently shown that simultaneous hepatic and pancreatic resection led to poor liver regeneration. As growth factors may be involved in these findings we compared the growth factor levels after liver resection with the levels in patients after pancreatic resection. Forty patients were accrued before hepatopancreatic surgery (hepatic resection n=20 and pancreatic resection n=20). Blood samples were taken from each patient immediately prior to surgery, during the operation and on the postoperative days (POD) 1-3, 5 and 10. To examine the wound fluid, liquid from the wound drains was collected on POD 3. Using ELISA the concentration of the angiogenic cytokines HGF and VEGF165 was determined. After the liver and pancreatic resections, circulating HGF and VEGF165 were increased. We found significantly higher levels of HGF on POD 1-3 (p<0.01), compared to preoperative results with a peak on POD 2. After measuring the postoperative VEGF165 levels we found significantly higher levels of circulating VEGF165 on POD 1-5 (p<0.01) compared to the preoperative levels. On comparing liver with pancreatic resection we did not detect significantly different levels of the two growth factors in the two groups. VEGF165 and HGF concentrations measured during the operation demonstrated no change. HGF and VEGF165 levels detected in the wound fluid on POD 3 were approximately 10 times higher than the preoperative serum levels, respectively. In summary, our data show increased VEGF165 and HGF levels after hepatopancreatic surgery. Notably, the lack of an impact of the type of organ resection on the concentration-time curve of the two growth factors suggest that high postoperative growth factor levels are part of normal wound healing and systemic inflammation. Thus, the proangiogenetic potential of growth factors may account for accelerated tumour growth when residual tumour cells are exposed to high levels of VEGF165 and HGF.

Indocyanine green disappearance rate is the most useful marker for liver resection.

BACKGROUND/AIMS: Non-invasive measurement of indocyanine green plasma disappearance rate (PDR(ICG)) is supposed to be an accurate liver function parameter. However, its value compared to conventional markers like bilirubin and prothrombin time (PT) is unclear. The authors therefore prospectively determined PDR(ICG) and bilirubin and PT and recorded the clinical course after liver resection. METHODOLOGY: Ninety-six patients underwent liver resection. Three patients died due to liver failure. Twenty patients (21%) developed signs of liver dysfunction. Receiver operating curve (ROC) analysis was performed to assess the value of each parameter to detect postoperative liver failure and dysfunction. RESULTS: PDR(ICG) and PT but not bilirubin preoperatively differentiated between patients with and without cirrhosis. In cirrhosis, PDR(ICG) patients did not recover to preoperative baseline values. ROC analysis revealed that PDR(ICG) [area under the curve (AUC): 0.867] did significantly better indicate postoperative liver dysfunction than bilirubin (AUC: 0.633) and PT (AUC: 0.570). CONCLUSIONS: PDR(ICG) should be measured preoperatively and daily after liver resection in patients at risk (underlying liver disease, resections > 30% standard liver volume).

Portal venous stasis during liver resection does not affect platelet aggregability.

INTRODUCTION: To reduce intraoperative blood loss in liver resections surgical bleeding control is often performed by a complete inflow obstruction of the liver called Pringle manoeuvre leading to a portal venous stasis. Platelet aggregability may be affected by this circulatory stasis. MATERIALS AND METHODS: A study population of 11 patients (37-67 years old, 7 females and 4 males) with hepatic tumours underwent elective liver resection. Pringle manoeuvre of up to 50 min duration was used in 4 patients. The other 7 patients were operated using selective vascular clamping. Platelets were aggregated before and after liver resection with adenosine diphosphate, collagen and ristocetin (according to Born). RESULTS: Mean maximal amplitudes of platelet aggregation were comparable before and after liver resection. Statistic analysis did not detect a significant difference between the values before and after liver resection as well as between Pringle manoeuvre and selective vascular clamping. CONCLUSION: Induced platelet aggregability is not affected by the method of surgical bleeding control used in liver resection. Platelet aggregability seems to be resistant even to portal venous stasis of up to 50 min during Pringle manoeuvre.

Central venous oxygen saturation does not correlate with the venous oxygen saturation at the surgical site during abdominal surgery.

INTRODUCTION: Measurement of central venous oxygen saturation has become a surrogate parameter for fluid administration, blood transfusions and treatment with catecholamines in (early) goal directed therapy in the treatment of acute septic patients. These strategies are not easily transferred to the postoperative management of abdominal surgery due to the different conditions in surgical patients. MATERIALS AND METHODS: A study population of 15 patients (8 females/7 males) underwent elective major abdominal surgery: 6 gastrectomies, 5 major liver resections and 4 lower anterior rectum resections. Surgery was performed for primary or secondary malignancy. The patients' age was 65.4+/-12.7 (mean+/-standard deviation, range 44-84, median 62) years. Blood samples were taken intraoperatively from indwelling central venous lines as well as from draining veins at the surgical site. Blood gas analyses to determine the oxygen saturations were performed immediately. All patients were operated in standardized general anesthesia including epidural analgesia and in a balanced volume status. RESULTS: Central venous oxygen saturations and oxygen saturations in blood from the draining veins of the surgical site showed a wide range with high intra- and interindividual differences intraoperatively. Overall, at most time points no correlation between the two oxygen saturations could be detected in three operation types. A significant correlation was only observed at one time point during liver resections. CONCLUSION: Our results show a lack of correlation between central venous oxygen saturations and oxygen saturations in the draining veins of the surgical site during major abdominal surgery. Measurement of central venous oxygen saturations does not seem to be a good surrogate for the local oxygen supply in the field of interest in major abdominal surgery even under standardized conditions.

Correlation of IL-8 with induction, progression and metastatic potential of colorectal cancer.

AIM: To investigate the expression profile of IL-8 in inflammatory and malignant colorectal diseases to evaluate its potential role in the regulation of colorectal cancer (CRC) and the development of colorectal liver metastases (CRLM). METHODS: IL-8 expression was assessed by quantitative real-time PCR (Q-RT-PCR) and the enzyme-linked immunosorbent assay (ELISA) in resected specimens from patients with ulcerative colitis (UC, n = 6) colorectal adenomas (CRA, n = 8), different stages of colorectal cancer (n = 48) as well as synchronous and metachronous CRLM along with their corresponding primary colorectal tumors (n = 16). RESULTS: IL-8 mRNA and protein expression was significantly up-regulated in all pathological colorectal entities investigated compared with the corresponding neighboring tissues. However, in the CRC specimens IL-8 revealed a significantly more pronounced overexpression in relation to the CRA and UC tissues with an average 30-fold IL-8 protein up-regulation in the CRC specimens in comparison to the CRA tissues. Moreover, IL-8 expression revealed a close correlation with tumor grading. Most interestingly, IL-8 up-regulation was most enhanced in synchronous and metachronous CRLM, if compared with the corresponding primary CRC tissues. Herein, an up to 80-fold IL-8 overexpression in individual metachronous metastases compared to normal tumor neighbor tissues was found. CONCLUSION: Our results strongly suggest an association between IL-8 expression, induction and progression of colorectal carcinoma and the development of colorectal liver metastases.

Penetration of moxifloxacin into liver tissue.

Moxifloxacin is considered for treatment of pyogenic liver abscesses as well as antibiotic prophylaxis in the case of hepatobiliary interventions. The aim of this study was to provide data on the pharmacokinetic (PK) profile of moxifloxacin in serum and liver tissue of patients undergoing liver resection due to primary or secondary tumours of the liver. Patients scheduled for liver resection (n=34) received moxifloxacin 400 mg at randomised time intervals prior to surgery. Blood and healthy liver tissue were sampled 1.5-26 h after administration of moxifloxacin. Immediately after centrifugation, plasma was separated, frozen and stored until analysis. In a subgroup of 19 patients, additional plasma specimens were obtained after 2, 4, 8, 12, 24, 36 and 48 h to assess the PK profile. PK parameters of moxifloxacin were calculated applying a two-compartment model. Median (interquartile range) PK parameters were as follows: peak concentration at the end of moxifloxacin infusion (C(max)), 6.0 mg/L (4.8-7.1 mg/L); area under the concentration-time curve extrapolated to infinity (AUC(0-∞)), 51.1 mgh/L (40.3-57.7 mgh/L); elimination half-life, 13.2h (11.0-14.1 h); volume of distribution at steady state (V(ss)), 138.7 L (102.7-168.5 L); and total body clearance (CL), 7.8 L/h (6.9-9.9L/h). Mean tissue concentrations were 9.13 mg/kg after 1.6-2.4 h, 7.62 mg/kg after 2.6-4.9h, 7.48 mg/kg after 5.6-10.0 h and 6.24 mg/kg after 22.9-26.5 h. Mean tissue:serum ratios were 2.9, 3.4, 5.0 and 12.3, respectively. The lowest tissue concentration found in the study at any time point was 2.8 mg/kg. In conclusion, moxifloxacin rapidly penetrates into the liver tissue where its concentration remains high following intravenous administration. Therefore, intravenously applied moxifloxacin might be used for the treatment of bacterial liver infections such as pyogenic liver abscess as well as in pre-operative prophylaxis.

Antibacterial [corrected] coating of abdominal closure sutures and wound infection.

BACKGROUND: Poor wound healing and the development of infection in incisional wounds continue to be among the most common complications of open abdominal surgery. Various bacteria may contaminate not only the tissue in the operative wound, but also the actual suture material. To prevent the contamination of suture material in surgical wounds, triclosan-coated polyglactin 910 suture materials with antibacterial activity (Vicryl plus) was developed. The aim of this study was to ascertain if the use of Vicryl plus reduced the number of wound infections after midline laparotomy comparing to polydioxanon suture (PDS II). METHODS: We performed 2,088 operations in our department between October 2004 and September 2006 via midline incision. In the first time period (TP1), a PDS II loop suture was used. In the second time period (TP2), we used Vicryl plus. All variables were recorded prospectively in a database. The primary outcome was the number of wound infections. Risk factors for poor wound healing were collected prospectively to compare the 2 groups. RESULTS: Using a PDS loop suture for abdominal wall closure in TP1, 10.8% of patients with wound infections were detected. The number of patients with wound infections decreased in TP2 using Vicryl plus for abdominal wall closure to 4.9% (P < .001) despite no other changes in protocols of patient care. Other risk factors for the development of site infections were comparable in the 2 groups. CONCLUSION: The use of antibiotic-coated loop suture for abdominal wall closure can decrease the number wound infections after abdominal surgery.