The TICAP-Study (titanium clips for appendicular stump closure): A prospective multicentre observational study on appendicular stump closure with an innovative titanium clip.

BACKGROUND: To evaluate the effectiveness and safety of the DS Titanium Ligation Clip for appendicular stump closure in laparoscopic appendectomy. METHODS: Overall, 502 patients undergoing laparoscopic appendectomy were recruited for this observational multicentre study in nine study centres between October 2011 and July 2013. The clip was finally applied in 390 patients. Primary outcome variables were feasibility of the clip, intra-abdominal surgical site (abscesses, stump leakages) and superficial wound infections. Patients were followed 30 days after surgery. RESULTS: The clip was applicable in nearly 80 % of patients. Reasons for not applying the clip were mainly an inflamed caecum or a too large diameter of the appendix base. Superficial wound infections were found in nine (2.31 %), intra-abdominal abscesses in five (1.28 %), appendicular stump leak in one (0.26 %), and other adverse events in 22 (5.64 %) patients. In total, 12 (3.08 %) patients were re-admitted to hospital for treatment. Seven re-admissions were surgery-related; ten (2.56 %) patients had to be re-operated. One patient died during the course of the study due to persisting peritonitis (mortality 0.26 %). CONCLUSIONS: The results suggest that the DS Titanium Ligation Clip is a safe and effective option in securing the appendicular stump in laparoscopic appendectomy. The complication rates found with the use of the DS-Clip are comparable to the rates in the literature when other methods are used. TRIAL REGISTRATION: NCT01734837 .

Critical appraisal of the International Study Group of Pancreatic Surgery (ISGPS) consensus definition of postoperative hemorrhage after pancreatoduodenectomy.

PURPOSE: Postpancreatectomy hemorrhage (PPH) is one of the most serious complications after pancreatoduodenectomy (PD). This study analyzed and validated the International Study Group of Pancreatic Surgery (ISGPS) definition of PPH and aimed to identify risk factors for early (<24 h) and late PPH. METHODS: Patients who underwent PD for pancreatic head tumors between 2001 and 2008 were included and complications were prospectively recorded. Factors associated with PPH were assessed by uni- and multivariate analysis. RESULTS: Complete datasets were available for 796 patients. Classic and pylorus-preserving PD was performed in 13.8% and 86.2% of the patients, respectively. According to the ISGPS definition, PPH occurred in 29.1% of the cases (232 of 796 patients): 4.8% grade A, 15.2% grade B, and 9.2% grade C. The definition is based largely on surrogate markers (e.g., transfusion requirement) that are affected by other critical illnesses and more than 97% of patients with mild PPH had no clinical signs of bleeding. The need for postoperative intensive care as well as the incidence of pancreatic fistula, relaparotomy, and mortality rates significantly increased from grades A to C. Thirty-seven patients (4.6%) required interventional (endoscopy or angiography) and/or relaparotomy for PPH. Relaparotomy for PPH was performed in 3.1% of all patients. Independent risk factors for early PPH were preoperative anemia (hemoglobin, <11 mg/dl) and multivisceral resection while advanced age, chronic renal insufficiency, increased blood loss, and long operation time were associated with late PPH. CONCLUSIONS: The ISGPS definition of PPH is feasible and applicable but produces a high rate of false positive mild PPH cases. The different grades still significantly correlate with relevant outcome variables, thus the definition discriminates postoperative courses, but a minor modification of the definition of mild PPH is suggested. The new results further demonstrate the need to optimize preoperative anemia and chronic renal insufficiency.

Risk-benefit assessment of closed intra-abdominal drains after pancreatic surgery: a systematic review and meta-analysis assessing the current state of evidence.

BACKGROUND: This systematic review aims to analyse the risk-benefit association of (1) prophylactic drains and/or (2) the time of their removal after pancreatic resection. MATERIALS AND METHODS: A systematic literature search (Medline, Embase, Biosis, and The Cochrane Library) was performed to identify all types of controlled trials comparing the role of drainage or the time of their removal on postoperative complications following pancreatic surgery. Meta-analysis was performed using a random-effects model. RESULTS: Four studies, two randomised trials and two prospective cohort studies, were included in the systematic review and meta-analysis. Removal of drains at day 5 or later did not show an influence on mortality, morbidity, re-intervention or hospital stay compared to no insertion of drains. Early (day 3-4) compared to late (≥ day 5) drain removal significantly reduced pancreatic fistulas (odds ratio (OR) 0.13; 95% confidence interval (CI) 0.03-0.32; P = 0.0002), intra-abdominal collections (OR 0.08; 95% CI 0.01-0.67; P = 0.02) and abscesses (OR 0.26; 95% CI 0.07-1.00; P = 0.05). Moreover, hospital stay was significantly reduced after early drain removal (mean difference -2.60 days; 95% CI -4.74 to -0.46; P = 0.02) CONCLUSION: Further randomised controlled trials are warranted to clarify whether drains are of any use. In case of drain insertion, early removal seems to be superior to late removal.

Adjuvant chemotherapy with fluorouracil plus folinic acid vs gemcitabine following pancreatic cancer resection: a randomized controlled trial.

CONTEXT: Adjuvant fluorouracil has been shown to be of benefit for patients with resected pancreatic cancer. Gemcitabine is known to be the most effective agent in advanced disease as well as an effective agent in patients with resected pancreatic cancer. OBJECTIVE: To determine whether fluorouracil or gemcitabine is superior in terms of overall survival as adjuvant treatment following resection of pancreatic cancer. DESIGN, SETTING, AND PATIENTS: The European Study Group for Pancreatic Cancer (ESPAC)-3 trial, an open-label, phase 3, randomized controlled trial conducted in 159 pancreatic cancer centers in Europe, Australasia, Japan, and Canada. Included in ESPAC-3 version 2 were 1088 patients with pancreatic ductal adenocarcinoma who had undergone cancer resection; patients were randomized between July 2000 and January 2007 and underwent at least 2 years of follow-up. INTERVENTIONS: Patients received either fluorouracil plus folinic acid (folinic acid, 20 mg/m(2), intravenous bolus injection, followed by fluorouracil, 425 mg/m(2) intravenous bolus injection given 1-5 days every 28 days) (n = 551) or gemcitabine (1000 mg/m(2) intravenous infusion once a week for 3 of every 4 weeks) (n = 537) for 6 months. MAIN OUTCOME MEASURES: Primary outcome measure was overall survival; secondary measures were toxicity, progression-free survival, and quality of life. RESULTS: Final analysis was carried out on an intention-to-treat basis after a median of 34.2 (interquartile range, 27.1-43.4) months' follow-up after 753 deaths (69%). Median survival was 23.0 (95% confidence interval [CI], 21.1-25.0) months for patients treated with fluorouracil plus folinic acid and 23.6 (95% CI, 21.4-26.4) months for those treated with gemcitabine (chi(1)(2) = 0.7; P = .39; hazard ratio, 0.94 [95% CI, 0.81-1.08]). Seventy-seven patients (14%) receiving fluorouracil plus folinic acid had 97 treatment-related serious adverse events, compared with 40 patients (7.5%) receiving gemcitabine, who had 52 events (P < .001). There were no significant differences in either progression-free survival or global quality-of-life scores between the treatment groups. CONCLUSION: Compared with the use of fluorouracil plus folinic acid, gemcitabine did not result in improved overall survival in patients with completely resected pancreatic cancer. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00058201.

Survival data justifies resection for pancreatic metastases.

BACKGROUND: Pancreatic metastases are uncommon and little is known about the oncologic outcome after resection or prognostic parameters. This study was designed to evaluate perioperative and follow-up results after resection for pancreatic metastases and to define prognostic factors. METHODS: From a prospective database, all consecutive resections performed at our institution for pancreatic metastases between October 2001 and July 2008 were identified. Clinicopathological details, perioperative, and follow-up results were analyzed. Uni- and multivariate analysis were performed to identify parameters associated with overall and disease-free survival. RESULTS: Forty-four resections were performed for pancreatic metastases. Primary tumors included 31 (70%) renal cell carcinomas (RCC) and 13 other primary tumors. Morbidity was 33% and mortality 4.4%. Pancreatic metastases occurred after a median interval of 6.9 years after resection of the primary tumor. Twenty-five patients (57%) had additional extrapancreatic disease. With a median follow-up of 32.1 months, overall 3- and 5-year survivals were 70.2% and 56.8%, disease-free 3- and 5-year survivals were 37.2% and 33%, respectively. Patients with isolated pancreatic metastases had an overall 3- and 5-year survival of 85.6% and 74.9%. Additional extrapancreatic disease, a disease-free interval of less than 36 months, and non-RCC entity were associated with shorter overall survival. Previous recurrence, non-RCC primary tumors, and a disease-free interval of less than 36 months were associated with shorter disease-free survival. CONCLUSIONS: Resection for pancreatic metastases can be performed safely and with good follow-up results and can be recommended as part of an interdisciplinary treatment. Especially in patients with isolated pancreatic metastases, long-term survival can be expected.

An open label randomized multicentre phase IIIb trial comparing parenteral substitution versus best supportive nutritional care in subjects with pancreatic adenocarcinoma receiving 5-FU plus oxaliplatin as 2nd or higher line chemotherapy regarding clinical benefit - PANUSCO.

BACKGROUND: Pancreatic cancer is an extremely aggressive malignancy. Subjects are afflicted with a variety of disconcerting symptoms, including profound cachexia. Recent data indicate that the outcome of oncological patients suffering from cancer cachexia could be improved by parenteral nutrition and that parenteral nutrition results in an improvement of quality of life and in prolonged survival. Currently, there is no recommendation of routine use of parenteral nutrition. Furthermore, there is no clear recommendation for 2nd line therapy (or higher) for pancreatic adenocarcinoma but often asked for. METHODS/DESIGN: PANUSCO is an open label, controlled, prospective, randomized, multicentre phase IIIb trial with two parallel arms. All patients will be treated with 5-fluorouracil, folinic acid and oxaliplatin on an outpatient basis at the study sites. Additionally, all patients will receive best supportive nutritional care (BSNC). In the experimental group BSNC will be expanded with parenteral nutrition (PN). In contrast, patients in the control group obtain solely BSNC. Parenteral nutrition will be applied overnight and at home by experienced medical staff. A total of 120 patients are planned to be enrolled. Primary endpoint is the comparison of the treatment groups with respect to event-free survival (EFS), defined as the time from randomization till time to development of an event defined as either an impairment (change from baseline of at least ten points in EORTC QLQ-C30, functional domain total score) or withdrawal due to fulfilling the special defined stopping criteria for chemotherapy as well as for nutritional intervention (NI) or death from any cause (whichever occurs first). DISCUSSION: The aim of this clinical trial is to evaluate whether parenteral nutrition in combination with defined 2nd line or higher chemotherapy has an impact on quality of life for patients suffering from pancreatic adenocarcinoma. TRIAL REGISTRATION: Current Controlled Trials ISRCTN60516908.

Left ventricular end-diastolic area is a measure of cardiac preload in patients with early septic shock.

BACKGROUND AND OBJECTIVE: Central venous pressure, intrathoracic blood volume, and left ventricular end-diastolic area are reliable measures of cardiac preload under stable clinical conditions. The purpose of this study was to compare different preload parameters over 24 h under conditions of multiple, frequently changing treatments in early septic shock. METHODS: In 28 mechanically ventilated patients within 6 h of the onset of septic shock, left ventricular end-diastolic area was measured using transoesophageal echocardiography. Intrathoracic blood volume, stroke volume variation, and central venous pressure were analysed as preload parameters. The relation between parameter changes and changes in therapy was examined with respect to cardiac index and stroke volume index. RESULTS: Regarding preload variables, linear regression analyses revealed a significant correlation between left ventricular end-diastolic area and stroke volume index (r=0.59, P<0.001) and cardiac index (r=0.41, P<0.001), respectively. Changes in left ventricular end-diastolic index and intrathoracic blood volume index reflected changes in the stroke volume index, whereas central venous pressure did not. Myocardial responsiveness also failed to predict changes in the stroke volume index. CONCLUSION: Only the left ventricular end-diastolic area index may help predict preload in ventilated patients with early septic shock.

Pharmacologic cholinesterase inhibition improves survival in experimental sepsis.

OBJECTIVE: Lethal sepsis occurs when an excessive inflammatory response evolves that cannot be controlled by physiologic anti-inflammatory mechanisms, such as the recently described cholinergic anti-inflammatory pathway. Here we studied whether the cholinergic anti-inflammatory pathway can be activated by pharmacologic cholinesterase inhibition in vivo. DESIGN: Prospective, randomized laboratory investigation that used an established murine sepsis model. SETTING: Research laboratory in a university hospital. SUBJECTS: Female C57BL/6 mice. INTERVENTIONS: Sepsis in mice was induced by cecal ligation and puncture. Animals were treated immediately with intraperitoneal injections of nicotine (400 microg/kg), physostigmine (80 microg/kg), neostigmine (80 microg/kg), or solvent three times daily for 3 days. MEASUREMENTS AND MAIN RESULTS: Treatment with physostigmine significantly reduced lethality (p < or = .01) as efficiently as direct stimulation of the cholinergic anti-inflammatory pathway with nicotine (p < or = .05). Administration of cholinesterase inhibitors significantly down-regulated the binding activity of nuclear factor-kappaB (p < or = .05) and significantly reduced the concentration of circulating proinflammatory cytokines tumor necrosis factor-alpha, interleukin-1beta, and interleukin-6 (p < or = .001), and pulmonary neutrophil invasion (p < or = .05). Animals treated with the peripheral cholinesterase inhibitor neostigmine showed no difference compared with physostigmine-treated animals. CONCLUSIONS: Our results demonstrate that cholinesterase inhibitors can be used successfully in the treatment of sepsis in a murine model and may be of interest for clinical use.

CXCL14 expression and potential function in pancreatic cancer.

CXC chemokines influence angiogenesis, growth, and metastatic potential of pancreatic cancer. Therefore, the expression and potential function of CXCL14, a recently described CXC chemokine, was evaluated. CXCL14 is upregulated in pancreatic cancer tissues compared to chronic pancreatitis and normal pancreas. Immunolocalization revealed a distinct expression of CXCL14 in tubular complexes in chronic pancreatitis and in particular at the invasive front of pancreatic cancer tissues. Stimulation of pancreatic cancer cells with CXCL14 showed no effects on cell viability and on chemosensitivity. However, CXCL14 clearly increased invasiveness of pancreatic cancer cells without affecting MMP-2 and VEGF secretion, whereas CXCL14 influenced NFkB p65 levels. In conclusion, CXCL14 might play a pivotal role in the pathobiology of pancreatic cancer, probably by regulating cancer invasion.

Expression and potential function of the CXC chemokine CXCL16 in pancreatic ductal adenocarcinoma.

CXC chemokines have a major influence on the angiogenesis, growth and metastatic potential of pancreatic ductal adenocarcinoma. CXCL16 is a unique transmembrane CXC chemokine, which is shed by members of the disintegrins and metalloproteases (ADAMs), in particular by ADAM10 and ADAM17. In our study, we evaluated expression and potential function of CXCL16 and its receptor CXCR6. CXCL16 and the receptor CXCR6 are upregulated in pancreatic ductal adenocarcinoma (PDAC) and chronic pancreatitis tissues in contrast to normal pancreatic tissues at the mRNA and protein levels. In 85 and 100% of the investigated samples, tumor cells showed positive immuno-staining for CXCL16 and CXCR6, respectively; furthermore, tubular complexes of chronic pancreatitis and the invasive front of PDAC were immunopositive for CXCL16 and CXCR6. Stimulation of PDAC cells with proinflammatory cytokines increased CXCL16 protein levels, whereas silencing of ADAM10 with siRNA transfection led to a decrease in CXCL16 protein levels in cell culture supernatants. No effects on cell viability were notable after incubation of cancer cells with CXCL16. However, CXCL16 markedly increased invasiveness of PDAC cells. Clinically, 82.5% of PDAC patients had higher CXCL16 serum values than the highest value seen in healthy donors. SELDI-TOF-MS analysis confirmed the upregulation of CXCL16 in sera of PDAC patients. In conclusion, CXCL16 in both transmembrane and soluble forms, and its receptor CXCR6, seem to play an important role in the pathobiology of pancreatic cancer and might be potential markers for pancreatic cancer diagnosis and a target for multimodal therapy concepts in the future.

Metastasis to the pancreas: characterization by morphology and contrast enhancement features on CT and MRI.

AIMS: To investigate the characteristics of metastasis to the pancreas using computed tomography (CT) and magnetic resonance imaging (MRI). METHODS: Twenty-two patients with metastases to the pancreas were examined preoperatively by MRI (7/22) and/or multidetector CT (15/22). Pre- and post-contrast images were acquired and morphology, size, and contrast enhancement of the tumor analyzed. Subsequently, all patients underwent surgery, and the histopathologic findings were compared with the imaging results. RESULTS: In 22 patients, a total of 29 metastases were found on CT and MRI. These metastases originated from renal cell carcinomas (RCC; 22/29), colorectal carcinoma (3/29), and other malignancies (4/29). The metastases differed not in size or location, but in their contrast enhancement characteristics. RCC metastases had either intense homogeneous enhancement (in small lesions) or rim enhancement (in large lesions). Outer regions of colorectal metastases showed no difference from normal pancreatic tissue, whereas the inner area showed hypo-enhancement due to central necrosis. CONCLUSION: Imaging features of metastases from RCC point to their primary origin. While they can be distinguished from primary adenocarcinoma of the pancreas, differentiation from endocrine carcinoma might be difficult. Differentiation of colorectal carcinoma remains to be investigated on larger numbers of cases.

R2 resection in pancreatic cancer--does it make sense?

BACKGROUND: The goal of surgical treatment in patients with pancreatic cancer is the complete resection of tumor tissue; however, the intraoperative appraisal of resectability can be difficult. Extensive surgical exploration for definitive clear resectability may lead to R2 resections in single cases. PATIENTS: We analyzed 38 patients with pancreatic cancer with remaining macroscopic tumor tissue after pancreatic resection, as R0 resection was not possible. Patients were compared to 46 patients with unresectable cancer without distant metastases or peritoneal carcinomatosis, in which a bypass procedure was performed. RESULTS: Operating time and hospital stay were significantly longer after R2 resection. Intraoperative blood loss was significantly higher; and severe surgical complications and the need for relaparotomy were significantly more frequent after R2 resection. The 30-day mortality rate was higher after R2 resection; this difference was not statistically significant. Median survival was comparable in both groups. Two years after surgery, 22.6% of the patients after R2 resection were still alive compared to 10.9% after bypass surgery. CONCLUSION: Tumor debulking is not a treatment option in patients with advanced pancreatic cancer, but the patient is not at a disadvantage compared to bypass procedures if tumor tissue remains and R0 resection cannot be achieved after surgical exploration.

Morphine-induced acute lung injury.

A 38-year-old woman who had familial adenomatous polyposis was admitted to the intensive care unit with an episode of severe sepsis 5 days after undergoing a pancreas-preserving duodenectomy. Laparotomy with removal of an intra-abdominal abscess, followed by closed postoperative continuous lavage for 10 days, was performed. During two courses of planned tracheal extubation, the patient developed an acute lung injury, making a reintubation necessary. In both events, the patient received small doses of continuous morphine before the extubation. Morphine may induce the development of an acute lung injury in patients, whereas the exact pathophysiologic and pharmacologic mechanisms remain unclear.

Mid-term absorbable monofilament is safe and effective for gastrointestinal anastomosis - PROMEGAT - A single-arm prospective observational study.

INTRODUCTION: Various suture materials and suture techniques are used to perform gastrointestinal anastomosis after tumour resection, but the best combination is still a matter of debate. METHODS: This multi-centre, international, single-arm, prospective observational study aimed at demonstrating the non-inferiority of a mid-term absorbable monofilament in comparison to braided sutures in gastrointestinal anastomosis. Monosyn suture was used to create the gastrointestinal anastomosis and the frequency of anastomotic leakage until day of discharge was chosen as the primary parameter. The outcome was compared to the results published for braided sutures in the literature. Secondary parameters were the time to perform the anastomosis, length of hospital stay, costs, and postoperative complications. RESULTS: The anastomosis leakage rate was 2.91%, indicating that Monosyn suture was not inferior to braided sutures used in gastrointestinal anastomosis. Of the reported anastomotic suture techniques, the single layer continuous method was the fastest and most economical technique in the present observational study. CONCLUSION: Monosyn suture is safe and effective in gastrointestinal anastomosis and represents a good alternative to other sutures used for gastrointestinal anastomosis. With regard to safety, time and cost-efficiency, the single-layer continuous technique should be considered a preferred method. The transfer of results from clinical studies into daily practice with regard to surgical techniques for gastrointestinal anastomosis should be further evaluated in larger studies or in nationwide registries.

Pharmacodynamics and organ storage of hydroxyethyl starch in acute hemodilution in pigs: influence of molecular weight and degree of substitution.

OBJECTIVE: To determine the differential influence of molecular weight and the degree of substitution of HES solutions on pharmacodynamics and pharmacokinetics including organ storage in a model of acute hemodilution in pigs. DESIGN: Prospective controlled randomized animal trial. INTERVENTIONS: After bleeding, 20 ml/kg, animals were substituted with 6% HES preparations (200/0.62, 200/0.5, and 100/0.5). MEASUREMENTS AND RESULTS: We did not observe any significant differences in the ability to sufficiently achieve plasma volume expansion and restoration of macrocirculation, nor maintenance of indicators of microcirculation between the groups. Urine production was significantly higher in HES-treated animals and highest in animals substituted with HES 100/0.5. Plasma clearance was measured under steady-state conditions with significantly reduced clearance for the HES 200/0.62 group compared with HES 100/0.5 and HES 200/0.5 (6.6 vs. 13.2 and 13.9 ml/min; P < or = 0.001), thus being dependent on the degree of substitution. Even after only 6 h, the amount of infused HES not detectable in either blood or urine was significantly higher in HES 200/0.62-treated animals (50.7% compared with HES 200/0.5 (28.8%), P = 0.020 and HES 100/0.5 (28.4%), P = 0.018), with its proportion rising over time. Finally, we could demonstrate considerable amounts of all HES solutions being stored in liver, kidney, lung, spleen and lymph nodes. CONCLUSIONS: All preparations analyzed sufficiently restored macro- and microcirculation; however, for all solutions relevant tissue storage of HES was observed after only 6 h.

Delayed gastric emptying (DGE) after pancreatic surgery: a suggested definition by the International Study Group of Pancreatic Surgery (ISGPS).

BACKGROUND: Delayed gastric emptying (DGE) is one of the most common complications after pancreatic resection. In the literature, the reported incidence of DGE after pancreatic surgery varies considerably between different surgical centers, primarily because an internationally accepted consensus definition of DGE is not available. Several surgical centers use a different definition of DGE. Hence, a valid comparison of different study reports and operative techniques is not possible. METHODS: After a literature review on DGE after pancreatic resection, the International Study Group of Pancreatic Surgery (ISGPS) developed an objective and generally applicable definition with grades of DGE based primarily on severity and clinical impact. RESULTS: DGE represents the inability to return to a standard diet by the end of the first postoperative week and includes prolonged nasogastric intubation of the patient. Three different grades (A, B, and C) were defined based on the impact on the clinical course and on postoperative management. CONCLUSION: The proposed definition, which includes a clinical grading of DGE, should allow objective and accurate comparison of the results of future clinical trials and will facilitate the objective evaluation of novel interventions and surgical modalities in the field of pancreatic surgery.

Postpancreatectomy hemorrhage (PPH): an International Study Group of Pancreatic Surgery (ISGPS) definition.

BACKGROUND: Postoperative hemorrhage is one of the most severe complications after pancreatic surgery. Due to the lack of an internationally accepted, universal definition of postpancreatectomy hemorrhage (PPH), the incidences reported in the literature vary considerably, even in reports from randomized controlled trials. Because of these variations in the definition of what constitutes a PPH, the incidences of its occurrence are not comparable. METHODS: The International Study Group of Pancreatic Surgery (ISGPS) developed an objective, generally applicable definition of PPH based on a literature review and consensus clinical experience. RESULTS: Postpancreatectomy hemorrhage is defined by 3 parameters: onset, location, and severity. The onset is either early (< or =24 hours after the end of the index operation) or late (>24 hours). The location is either intraluminal or extraluminal. The severity of bleeding may be either mild or severe. Three different grades of PPH (grades A, B, and C) are defined according to the time of onset, site of bleeding, severity, and clinical impact. CONCLUSIONS: An objective, universally accepted definition and clinical grading of PPH is important for the appropriate management and use of interventions in PPH. Such a definition also would allow comparisons of results from future clinical trials. Such standardized definitions are necessary to compare, in a nonpartisan manner, the outcomes of studies and the evaluation of novel operative treatment modalities in pancreatic surgery.

Blockade of the chemokine receptor CXCR2 inhibits pancreatic cancer cell-induced angiogenesis.

A central feature of all solid tumor growth is the presence of neovascularization. The CXC chemokines GRO-gamma/CXCL3, ENA-78/CXCL5, and IL-8/CXCL8 have profound angiogenic potential mediated through the CXCR2 receptor. The aim of the present study was to evaluate the expression of the angiogenic chemokines in three human pancreatic cancer cell lines and to determine the role of these proteins in pancreatic cancer angiogenesis. Secreted CXC protein levels in the supernatant of the cell lines were analyzed by ELISA. A rat corneal micropocket model was used to determine the angiogenic potential of these secreted CXC chemokines in vivo. ELISA confirmed expression of all three tested CXC chemokines in the supernatant of two cell lines. In the corneal micropocket assay, neovascularization was induced using pelleted supernatant of all three-cell lines. Using an anti-CXCR2 antibody, neovascularization was significantly inhibited in the high expressing BxPC-3 cell line samples. In addition, the expression of ENA-78/CXCL5 and IL-8/CXCL8 has been evaluated in human pancreatic cancer tissue samples by using immunohistochemistry in order to further investigate the potential role of CXC chemokines in pancreatic cancer angiogenesis and tumorigenesis.

Center for clinical studies in a surgical department--an approach for more evidence-based medicine.

The concept of evidence-based medicine (EBM) has been introduced into the field of surgery in Germany since 1996, initially focussing on the application of the classical five-step-concept of EBM to the individual patient. Despite the international efforts of the Cochrane Collaboration, few systematic reviews address surgical procedures and the number of high quality randomized-controlled trials (RCTs) are low. External evidence in surgery is a major problem and requires new strategies in research and patient care. Therefore, in the Department of Surgery at the University of Heidelberg a clinical trial unit was founded to create more evidence via two approaches. First, patients admitted to hospital should be treated within RCTs. Since May 2002 1808 patients have been enrolled into a total of 38 pharmaceutical (19 trials with 470 patients enrolled) and investigator initiated (19 trials with 1338 patients enrolled) studies. Second, the clinical site develops and conducts surgical efficacy RCTs and follows new standards including publication and registration of the protocols. Within 3 years it was possible to change practice in an academic setting from the traditional concept to an evidence-based approach.

Ruptured angiosarcoma of the liver treated by emergency catheter-directed embolization.

Angiosarcoma is a rare primary malignant neoplasm of the liver with a poor prognosis. Here, we report a case of a patient with a ruptured hepatic angiosarcoma which was treated by emergency catheter-directed embolization, followed by left-sided hemihepatectomy.