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H Friess

Publications and source records attributed to H Friess.

At least 37 records · Page 2Linked to original sources
PubMed2005

Osteopontin influences the invasiveness of pancreatic cancer cells and is increased in neoplastic and inflammatory conditions.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive malignancies, with an overall 5-year survival rate of less than 5%. Invasive tumor growth and early metastasis are two important reasons for this dismal prognosis. Osteopontin (OPN) is a secretory protein with a variety of functions, for example in cell adhesion and migration, inflammatory reaction and apoptosis. In this study the functional role of OPN in human pancreatic cancer and its potential use as a disease marker were analyzed. By real time quantitative PCR, there was a 2.2-fold and 1.6-fold increase of OPN mRNA in pancreatic cancers (n = 23) and chronic pancreatitis samples (n = 22), respectively, compared to normal pancreatic tissues (n = 20). Immunohistochemical analysis demonstrated OPN staining in 60% of the primary pancreatic tumors and in 72% of the lymph node and liver metastases. ELISA analysis of serum samples obtained from pancreatic cancer patients (n = 70), chronic pancreatitis patients (n = 12), and healthy donors (n = 20) showed a 1.6-fold increase in OPN serum levels in patients with tumors and a 1.9-fold increase in patients with chronic pancreatitis. Recombinant human OPN significantly increased the invasiveness of pancreatic cancer cells, without having any impact on cell proliferation. In addition, down regulation of OPN by specific siRNA molecules decreased pancreatic cancer cell invasion. In conclusion, OPN serum levels in pancreatic cancer and chronic pancreatitis patients are not significantly different, thereby restricting its role as a prognostic or follow-up marker. Our results do suggest, however, that blockade of OPN might be useful as a therapeutic approach to inhibit invasion and metastasis of pancreatic cancer cells.

Adenocarcinoma↗
PubMed2005

Randomized clinical trial of pylorus-preserving duodenopancreatectomy versus classical Whipple resection-long term results.

BACKGROUND: It is not known whether pylorus-preserving duodenopancreatectomy is as effective as the classical Whipple procedure in the resection of pancreatic and periampullary tumours. A prospective randomized trial was undertaken to compare the results of the two procedures. METHODS: Clinical data, histological findings, short-term results, survival and quality of life of all patients having surgery for suspected pancreatic or periampullary cancer between June 1996 and September 2001 were analysed. RESULTS: Two hundred and fourteen patients were randomized to undergo either a standard or a pylorus-preserving Whipple resection. After exclusion of 84 patients on the basis of intraoperative findings, 130 patients (66 standard Whipple operation and 64 pylorus-preserving resection) were entered into the trial. Of these, 110 patients with proven adenocarcinoma (57 standard Whipple and 53 pylorus-preserving resection) were analysed for long-term survival and quality of life. There was no difference in perioperative morbidity. Long-term survival, quality of life and weight gain were identical after a median follow-up of 63.1 (range 4-93) months. At 6 months, capacity to work was better after the pylorus-preserving procedure (77 versus 56 per cent; P = 0.019). CONCLUSION: Both procedures were equally effective for the treatment of pancreatic and periampullary cancer. Pylorus-preserving Whipple resection offers some minor advantages in the early postoperative period, but not in the long term.

Adult↗
PubMed2005

[Technique of pancreas-preserving duodenectomy].

Even in pancreatic surgery, as in other organs, there is a tendency towards subtle organ-preserving techniques. Benign duodenal tumors which cannot be resected transduodenally or multiple dysplastic duodenal adenomas in patients with familial adenomatous polyposis (FAP) usually require partial pancreaticoduodenectomy. However, pancreas-preserving duodenectomy may represent a viable alternative. This technique allows for the resection of the entire duodenum without resection of the pancreatic head. Large duodenal adenomas, multiple adenomas with dysplasia in patients with FAP, and based on the literature extended duodenal injury after trauma may represent indications for this surgical technique. Compared with duodenopancreatectomy, this intervention can be performed with a comparably low morbidity and leads to good functional results. Beside the preservation of pancreatic parenchyma and the reduction of the number of anastomoses, this technique offers the advantage of uncomplicated endoscopic follow-up. In this article we describe the surgical technique of pancreas-preserving duodenectomy and our experience with this intervention.

Adenoma↗
PubMed2005

[Diagnostics for diseases of the gallbladder and biliary tract from the viewpoint of the internist and surgeon. Demands made on radiological diagnostics].

Jaundice and colic pain of the right upper quadrant are the main symptoms of biliary diseases. Gallstone-related diseases often lead to hospital admission. The evaluation of a patient with biliary symptoms requires a combination of history taking, physical examination, laboratory analysis, and imaging modalities. A high-quality magnetic resonance imaging (MRI) or computed tomography (CT) scan is usually sufficient to evaluate a patient with painless jaundice. Ultrasonography is helpful as an initial screening test to guide the diagnostic work-up. Invasive methods (e.g., ERCP) are mainly used for palliation of patients with incurable disease.

Aged↗
PubMed2005

[Abdominal trauma].

Blunt abdominal trauma is much more frequent than penetrating abdominal trauma in Europe. As a consequence of improved quality of computed tomography, even complex liver injuries are increasingly being treated conservatively. However, missed hollow viscus injuries still remain a problem, as they considerably increase mortality in multiply injured patients. Laparoscopy decreases the rate of unnecessary laparotomies in perforating abdominal trauma and helps to diagnose injuries of solid organs and the diaphragm. However, the sensitivity in detecting hollow viscus injuries is low and the role of laparoscopy in blunt abdominal injury has not been defined. If intra-abdominal bleeding is difficult to control in hemodynamically unstable patients, damage control surgery with packing of the liver, total splenectomy, and provisional closure of hollow viscus injuries is of importance. Definitive surgical treatment follows hemodynamic stabilization and restoration of hemostasis. Injuries of the duodenum and pancreas after blunt abdominal trauma are often associated with other intra-abdominal injuries and the treatment depends on their location and severity.

Abdominal Injuries↗
PubMed2005

Guidelines for prevention and management of complications following kidney transplantation in rats.

Kidney transplantation in rats is a useful model for microsurgery, transplantation, and immunology studies. Our aim was to analyze various techniques of kidney transplantation in rats with emphasis on guidelines for the prevention and management of complications. Complications were categorized into general, vascular, and urological types and respectively attributed to long transplantation time, core body temperature drop, nonreplaced intraoperative blood loss, anastomosis failure, and ureteral anastomoses with stents or cannulas, which increase the risk of calculus formation. In conclusion, to decrease the complication rates the animal should be placed on a heating pad. For hemodynamic stability NaCl should be administered subcutaneously. To reduce the risk of thrombosis, ice-cold saline containing heparin should be administered. Vascular complications, which mainly depend on the microsurgeon's expertise, can be prevented by meticulous surgical technique (preferably an end-in-end anastomosis). The main urinary complications can be minimized by avoiding stents and cannulas and focusing on using techniques like the bladder-patch technique.

Animal Husbandry↗
PubMed2005

Gender-specific expression of liver organic anion transporters in rat.

BACKGROUND: Sex differences in drug pharmacokinetics have been well recognized and gender has been considered a risk factor for adverse events to medications. The aim of this study was to investigate the effect of gender on the expression of hepatocellular transport proteins involved in uptake and secretion of organic anions in rat. MATERIALS AND METHODS: Expression of the rat liver organic anion transporting polypeptides (Oatps) and multidrug resistance proteins (Mrps) was analysed by reverse transcription polymerase chain reaction (RT-PCR), immunoblot analysis and immunofluorescence microscopy in male and female rats. Regulation of these transport proteins in response to the steroid dehydroepiandrosterone (DHEA) was investigated. RESULTS: In untreated rats, protein expression significantly differed between genders being higher (Mrp2, Mrp3), comparable [Oatp1a1 (Oatp1); Oatp1b2 (Oatp4)] or lower [Oatp1a4 (Oatp2)] in female than in male rat. DHEA treatment over 3 days (100 mg d(-1)) led to a further increase in Mrp3 expression only in female rats. Mrp2 expression was not influenced by DHEA treatment. Oatp1a1 and Oatp1b2 were significantly down-regulated after DHEA treatment in both male and female rats. In contrast, Oatp1a4 was down-regulated in male rats only. CONCLUSIONS: In rat, liver transport proteins of the Oatp and Mrp family are expressed and regulated in a gender-specific manner according to sexual differences in the hepatic metabolism of steroids and drugs. These findings may partly explain the well-known sex differences in hepatic handling of organic anions.

ATP Binding Cassette Transporter, Subfamily B↗
PubMed2005

Polymorphisms of UDP-glucuronosyltransferase 1A7 are not involved in pancreatic diseases.

BACKGROUND: Xenobiotic mediated cellular injury is thought to play a major role in the pathogenesis of pancreatic diseases. Genetic variations that reduce the expression or activity of detoxifying phase II biotransformation enzymes such as the UDP-glucuronosyltransferases might be important in this respect. Recently, a UGT1A7 low detoxification activity allele, UGT1A7*3, has been linked to pancreatic cancer and alcoholic chronic pancreatitis. OBJECTIVE: To investigate whether UGT1A7 polymorphisms contribute to the risk of pancreatitis and pancreatic cancer. METHODS: Genetic polymorphisms in the UGT1A7 gene were assessed in a large cohort of patients with different types of pancreatitis and pancreatic cancer originating from the Czech Republic (n = 93), Germany (n = 638), Netherlands (n = 136), and Switzerland (n = 106), and in healthy (n = 1409) and alcoholic (n = 123) controls from the same populations. Polymorphisms were determined by melting curve analysis using fluorescence resonance energy transfer probes. In addition, 229 Dutch subjects were analysed by restriction fragment length polymorphism. RESULTS: The frequencies of UGT1A7 genotypes did not differ between patients with acute or chronic pancreatitis or pancreatic adenocarcinoma and alcoholic and healthy controls. CONCLUSIONS: The data suggest that, in contrast to earlier studies, UGT1A7 polymorphisms do not predispose patients to the development of pancreatic cancer and pancreatitis.

Adenocarcinoma↗
PubMed2005

Clinical impact of cachexia on survival and outcome of cancer patients.

Approximately one half of all cancer patients experience a complex metabolic status involving progressive exhaustion of adipose and skeletal muscle tissue. This condition, known as cachexia, is responsible for more than 20% of the overall deaths in cancer patients. Although its main mechanisms remain unknown, several hypotheses have been proposed. One of the pathogenic mechanisms involves leptin and hypothalamic neuropeptide-containing pathways. Orexigenic and anorexigenic neuropeptides are down-regulated respectively upregulated as a result of cancer. Other pathogenic theories consider tumour derived factors, such as LMF (Lipid Mobilising Factor) and PIF (Proteolysis-inducing Factor), to be responsible for the weight losing pattern of cancer patients via activation of various catabolic pathways (e.g. ubiquitin-proteasome proteolytic-pathway, etc.). Despite the controversial discussion of cachexia-inducing mechanisms it is clear that proinflammatory cytokines, such as TNFalpha, IFNgamma, IL-1, IL-6 and IL-8, are linked to all pathways that induce cachexia. Although only limited treatment exists for patients with cancer cachexia, recent studies with eicosapaentanoic acid showed promising effects in reversing weight losing pattern of cachectic patients. Cytokine targeted monoclonal antibodies, cytokine traps and genetic therapies are also evaluated for future therapeutic strategies.

Cachexia↗
PubMed2004

Phosphatidylinositol 3-kinase regulates Ca2+ signaling in pancreatic acinar cells through inhibition of sarco(endo)plasmic reticulum Ca2+-ATPase.

Calcium is a key mediator of hormone-induced enzyme secretion in pancreatic acinar cells. At the same time, abnormal Ca(2+) responses are associated with pancreatitis. We have recently shown that inhibition of phosphatidylinositol 3-kinase (PI3-kinase) by LY-294002 and wortmannin, as well as genetic deletion of PI3-kinase-gamma, regulates Ca(2+) responses and the Ca(2+)-sensitive trypsinogen activation in pancreatic acinar cells. The present study sought to determine the mechanisms of PI3-kinase involvement in Ca(2+) responses induced in these cells by CCK and carbachol. The PI3-kinase inhibitors inhibited both Ca(2+) influx and mobilization from intracellular stores induced by stimulation of acini with physiological and pathological concentrations of CCK, as well as with carbachol. PI3-kinase inhibition facilitated the decay of cytosolic free Ca(2+) concentration ([Ca(2+)](i)) oscillations observed in individual acinar cells. The PI3-kinase inhibitors decreased neither CCK-induced inositol 1,4,5-trisphosphate [Ins(1,4,5)P(3)] production nor Ins(1,4,5)P(3)-induced Ca(2+) mobilization, suggesting that the effect of PI3-kinase inhibition is not through Ins(1,4,5)P(3) or Ins(1,4,5)P(3) receptors. PI3-kinase inhibition did not affect Ca(2+) mobilization induced by thapsigargin, a specific inhibitor of sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA). Moreover, SERCA blockade with thapsigargin abolished the effects of pharmacological and genetic PI3-kinase inhibition on [Ca(2+)](i) signals, suggesting SERCA as a downstream target of PI3-kinase. Both pharmacological PI3-kinase inhibition and genetic deletion of PI3-kinase-gamma increased the amount of Ca(2+) in intracellular stores during CCK stimulation. Finally, addition of the PI3-kinase product phosphatidylinositol 3,4,5-trisphosphate to permeabilized acini significantly attenuated Ca(2+) reloading into the endoplasmic reticulum. The results indicate that PI3-kinase regulates Ca(2+) signaling in pancreatic acinar cells through its inhibitory effect on SERCA.

Animals↗
PubMed2004

Endothelin receptor antagonists are not beneficial in the therapy of acute experimental pancreatitis.

BACKGROUND AND AIM: Due to increased capillary permeability and the early appearance of vasoactive and toxic agents, patients suffering from necrotizing pancreatitis frequently develop a systemic inflammatory response syndrome (SIRS). Endothelin, a potent vasoconstrictor, is thought to play a major role in these changes via the regulation of microcirculation. An improved outcome of acute experimental necrotizing pancreatitis by blocking the endothelin receptors ETA and ETB, either selectively (only ETA) or unselectively (ETA and ETB), has been suggested. The aim of this study was to investigate further the beneficial effects of new, highly potent endothelin-receptor (ET-R) antagonists in acute experimental pancreatitis. METHODS: The influence of the selective ET-RA antagonist BSF208075 (1 mg/kg) on mortality was studied in three severity groups of acute necrotizing pancreatitis (retrograde injection of 4%, 5% and 6% of sodium taurocholate into the main pancreatic duct). The effects of the selective ET-RA antagonists LU135252 (LU13) and BSF208075 (BSF20) and of the unselective endothelin receptor (ET-R(A/B)) antagonist BSF420627 (BSF42) were additionally analyzed in 4% taurocholate-induced necrotizing pancreatitis. Furthermore, the significance of variable doses of the endothelin receptor antagonist LU13 (1 mg/kg, 3 mg/kg and 100 mg/kg) was determined in a 4% sodium taurocholate model and in a cerulein pancreatitis model. RESULTS: Prophylactic ET-R antagonism increased the mortality rate in the 4% sodium taurocholate-induced pancreatitis. No reduction in pancreatic damage after induction of taurocholate pancreatitis was found by ET-R blockage. Application of ET-R antagonists had no beneficial influence in ascites development. However, administration of LU13 (100 mg/kg) resulted in a non-significant increase in pancreatic oedema, whereas peritoneal necrosis was not affected. CONCLUSION: The selective and unselective ET-R antagonists BSF20, BSF42 and LU13 failed to improve survival and pancreatic damage during acute experimental pancreatitis. Therefore, previously reported beneficial effects of ET-R antagonists in experimental acute pancreatitis have to be critically evaluated before conclusions for further clinical development are made.

Animals↗
PubMed2004

Curative resection is the single most important factor determining outcome in patients with pancreatic adenocarcinoma.

BACKGROUND: Mortality rates associated with pancreatic resection for cancer have steadily decreased with time, but improvements in long-term survival are less clear. This prospective study evaluated risk factors for survival after resection for pancreatic adenocarcinoma. METHODS: Data from 366 consecutive patients recorded prospectively between November 1993 and September 2001 were analysed using univariate and multivariate models. RESULTS: Fifty-eight patients (15.8 per cent) underwent surgical exploration only, 97 patients (26.5 per cent) underwent palliative bypass surgery and 211 patients (57.7 per cent) resection for pancreatic adenocarcinoma. Stage I disease was present in 9.0 per cent, stage II in 18.0 per cent, stage III in 68.7 per cent and stage IV in 4.3 per cent of patients who underwent resection. Resection was curative (R0) in 75.8 per cent of patients. Procedures included pylorus-preserving Whipple resection (41.2 per cent), classical Whipple resection (37.0 per cent), left pancreatic resection (13.7 per cent) and total pancreatectomy (8.1 per cent). The in-hospital mortality and cumulative morbidity rates were 2.8 and 44.1 per cent respectively. The overall actuarial 5-year survival rate was 19.8 per cent after resection. Survival was better after curative resection (R0) (24.2 per cent) and in lymph-node negative patients (31.6 per cent). A Cox proportional hazards survival analysis indicated that curative resection was the most powerful independent predictor of long-term survival. CONCLUSION: Resection for pancreatic adenocarcinoma can be performed safely. The overall survival rate is determined by the radicality of resection. Patients deemed fit for surgery who have no radiological signs of distant metastasis should undergo surgical exploration. Resection should follow if there is a reasonable likelihood that an R0 resection can be obtained.

Adenocarcinoma↗
PubMed2004

[Duodenum-preserving pancreas head resection-an operative technique for retaining the organ in the treatment of chronic pancreatitis].

Chronic pancreatitis is an inflammatory disease characterized by the progressive conversion of pancreatic parenchyma to fibrous tissue. The most frequent causes are alcohol overconsumption and anatomic variants such as pancreas divisum, cholelithiasis, and individual genetic predisposition. The process of fibrosis with consecutive loss of pancreatic parenchyma leads to exocrine insufficiency and maldigestion and, in advanced stages of the disease, to diabetes mellitus. Beside exocrine and endocrine malfunction, mechanical complications occur such as the formation of pancreatic pseudocysts and duodenal and common bile duct obstruction. About 50% of patients with chronic pancreatitis need surgical intervention due to untreatable chronic pain. As recent investigations suggest that the head of the pancreas triggers the chronic inflammatory process, resection of this inflammatory mass must be regarded as pivotal in any surgical intervention. Radical techniques such as the Whipple procedure are undoubtedly successful regarding pain reduction but, even in its pylorus-preserving variant, associated with high postoperative morbidity due to a large loss of pancreatic parenchyma and the absence of duodenal passage. Thirty years ago, H.G. Beger described for the first time the technique of duodenum-preserving pancreatectomy, which better combines resection of the pancreatic head with low morbidity. Over the years, different variations of the original Beger technique (Frey, Izbicky, Berne modification) have been developed, and the excellent results obtained with these methods underline that organ-sparing techniques should be preferred in the surgical treatment of chronic pancreatitis.

Chronic Disease↗
PubMed2004

[Kausch-Whipple pancreaticoduodenectomy. Technique and results].

The Kausch-Whipple operation is the standard procedure for resection of pancreatic head cancer, distal bile duct cancer, and periampullary cancers. It is also used for some cases of chronic pancreatitis. Traditionally, this operation is associated with high perioperative morbidity and mortality. The aim of our study was to present our current technique for Kausch-Whipple pancreaticoduodenectomy and to demonstrate that acceptable perioperative and long-term outcomes can be achieved by a standardised technique in a high-volume centre.

Follow-Up Studies↗
PubMed2004

Desmoplastic reaction in pancreatic cancer: role of pancreatic stellate cells.

OBJECTIVES: Pancreatic cancer has a very poor prognosis, largely due to its propensity for early local and distant spread. Histopathologically, most pancreatic cancers are characterized by a prominent stromal/fibrous reaction in and around tumor tissue. The aims of this study were to determine whether (1) the cells responsible for the formation of the stromal reaction in human pancreatic cancers are activated pancreatic stellate cells (PSCs) and (2) an interaction exists between pancreatic cancer cells and PSCs that may facilitate local and distant invasion of tumor. METHODS: Serial sections of human pancreatic cancer tissue were stained for desmin and glial fibrillary acidic protein (stellate cell selective markers) and alpha-smooth muscle actin (alphaSMA), a marker of activated PSC activation, by immunohistochemistry, and for collagen using Sirius Red. Correlation between the extent of positive staining for collagen and alphaSMA was assessed by morphometry. The cellular source of collagen in stromal areas was identified using dual staining methodology, ie, immunostaining for alphaSMA and in situ hybridization for procollagen alpha1I mRNA. The possible interaction between pancreatic cancer cells and PSCs was assessed in vitro by exposing cultured rat PSCs to control medium or conditioned medium from 2 pancreatic cancer cell lines (PANC-1 and MiaPaCa-2) for 24 hours. PSC activation was assessed by cell proliferation and alphaSMA expression. RESULTS: Stromal areas of human pancreatic cancer stained strongly positive for the stellate cell selective markers desmin and GFAP (indicating the presence of PSCs), for alphaSMA (suggesting that the PSCs were in their activated state) and for collagen. Morphometric analysis demonstrated a close correlation (r = 0.77; P < 0.04; 8 paired sections) between the extent of PSC activation and collagen deposition. Procollagen mRNA expression was localized to alphaSMA-positive cells in stromal areas indicating that activated PSCs were the predominant source of collagen in stromal areas. Exposure of PSCs to pancreatic cancer cell secretions in vitro resulted in PSC activation as indicated by significantly increased cell proliferation and alphaSMA expression. CONCLUSIONS: Activated PSCs are present in the stromal reaction in pancreatic cancers and are responsible for the production of stromal collagen. PSC function is influenced by pancreatic cancer cells. Interactions between tumor cells and stromal cells (PSCs) may play an important role in the pathobiology of pancreatic cancer.

Actins↗
PubMed2004

Loss of heterozygosity in the HLA class I region in human pancreatic cancer.

An altered human leukocyte antigen (HLA) class I expression constitutes an important tumor-escape mechanism counteracting T-cell mediated immune responses. We utilized the technique of microsatellite analysis to characterize the loss of heterozygosity (LOH) in the HLA class I region in 24 samples of patients with human ductal pancreatic carcinoma. The expression of HLA class I and the infiltration by T cells were studied in parallel by standard immunohistochemistry. The present study demonstrates LOH in the HLA class I region in five patients with pancreatic carcinoma. Immunohistochemical analysis showed that pancreatic carcinomas were frequently characterized by a total or partial loss of expression in HLA class I antigen. The positive or negative LOH status corresponded with the expression analysis in eight cases. Reduction of HLA class I expression without LOH was found in 14 cases. Lymphocyte infiltration with CD3+, CD4+, and CD8+ T cells did not show significant differences between LOH-positive and LOH-negative tumors. In conclusion, LOH does not seem to be the only factor for the reduced expression of HLA class I antigen as well as for the T-cell infiltration in this type of tumor.

CD3 Complex↗
PubMed2004

RUNX3 expression in primary and metastatic pancreatic cancer.

AIM: Runx transcription factors are important regulators of lineage specific gene expression, cell proliferation, and differentiation. Runx3 expression is lost in a high proportion of gastric cancers, suggesting a tumour suppressive role in this malignancy. This study investigates the expression and localisation of Runx3 in pancreatic tissues. METHODS: Quantitative polymerase chain reaction was used to measure Runx3 mRNA. Immunohistochemistry was carried out to localise Runx3 in normal pancreatic tissues, and in primary and metastatic pancreatic ductal adenocarcinoma (PDAC). Basal and transforming growth factor beta1 (TGFbeta1) induced Runx3 expression was analysed in cultured pancreatic cancer cell lines. RESULTS: Runx3 expression was low to absent in normal pancreatic tissues, but increased in a third of cancer tissues. Runx3 was present only in islets in normal pancreas, whereas in pancreatic cancers, Runx3 was detected in the cancer cells of seven of 24 samples analysed. In addition, it was expressed by lymphocytes in six of the 16 cases with lymphocyte infiltration. In pancreatic cancer cell lines, Runx3 mRNA was present in Colo-357 and T3M4 cells, but was low to absent in the other cell lines tested. TGFbeta1 repressed Runx3 mRNA expressed in Colo-357 cells, and had no effect on Runx3 expression in the other pancreatic cancer cell lines. CONCLUSION: Runx3 expression is restricted to islets in the normal pancreas. In contrast, a considerable proportion of pancreatic tumours express Runx3, and its expression is localised in the tumour cells and in the infiltrating lymphocytes. Thus, Runx3 might play a role in the pathogenesis of PDAC.

Adenocarcinoma↗