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H Friess

Publications and source records attributed to H Friess.

At least 253 records · Page 14Linked to original sources
PubMed1996

A pancreatic cancer-specific expression profile.

We present an approach making use of technology established in the context of the genome project to describe a pancreatic cancer-specific expression profile and to identify new potential disease genes or disease-associated-genes. By use of gridded arrays of pancreatic cancer cDNA libraries and differential hybridizations we show that 4% the gridded cDNA library clones contain sequences preferentially expressed in pancreatic cancer. EST-sequencing of 369 distinct (408 total), differentially expressed sequences identified novel genes (32.5%) or homologs to EST-sequences with unknown function (26.3%). Homologies to known genes allow to determine a pancreatic cancer-specific expression profile, which provides for the first time evidence for complex primary and secondary alterations of gene expression responsible for the development of the phenotype of pancreatic cancer cells. In addition this has led to the identification of novel differentially expressed genes, which represent potential oncogenes or disease-associated markers and may be helpful for the development of therapeutic or diagnostic modalities.

Animals↗
PubMed1996

Attenuated ALK5 receptor expression in human pancreatic cancer: correlation with resistance to growth inhibition.

Transforming growth factor-beta (TGF-beta) receptors constitute a family of transmembrane proteins that bind TGF-beta ligands. In this study we assessed the growth responsiveness to TGF-beta 1 in pancreatic cancer cell lines and characterized the levels of expression of TGF-beta receptors in these cell lines and in human pancreatic cancer tissues. COLO 357 cells were most sensitive to the growth inhibitory actions of TGF-beta 1, PANC-1 cells exhibited moderate sensitivity, Hs766T cells exhibited slight sensitivity and MIA PaCa-2 and T3M4 cells were resistant to TGF-beta 1. Only COLO 357 cells expressed high levels of ALK5, the major type I TGF-beta receptor (T beta RI). Hs766T and PANC-1 cells expressed high levels of SKR1, another T beta RI subtype. Only MIA PaCa-2 cells did not exhibit the type II TGF-beta receptor (T beta-RII) transcript, whereas type III TGF-beta receptor (T beta-RIII) mRNA levels were elevated in this cell line and in HS766T cells. All the cell lines expressed TGF-beta 1, but TGF-beta 2 and TGF-beta 3 mRNA levels were variable. ALK5 and SKR1 mRNA levels were 6.8- and 9-fold greater in the pancreatic tumors in comparison with the corresponding levels in the normal pancreas. However, in the cancer cells, ALK5 immunoreactivity was faint, whereas T beta RII immunoreactivity was focal and intense. Conversely, in ductal cells adjacent to cancer cells ALK5 immunoreactivity was strong, whereas T beta RII immunoreactivity was weak. Since ALK5 heterodimerization with T beta RII is crucial for TGF-beta-mediated signaling, our findings suggest that low levels of ALK5 in pancreatic cancer cells within a tumor may protect against growth inhibition.

Adolescent↗
PubMed1996

Co-expression of heparin-binding EGF-like growth factor and related peptides in human gastric carcinoma.

Heparin-binding epidermal growth factor (EGF)-like growth factor (HB-EGF) is a member of the EGF family of polypeptide growth factors, which includes EGF, transforming growth factor alpha(TGF-alpha), amphiregulin (AR) and betacellulin (BTC). To assess the potential role of HB-EGF in human gastric carcinomas, the expression of HB-EGF and EGF receptor (EGF-R) was examined in normal and cancerous gastric tissues and cultured gastric cancer cell lines. By Northern blot analysis, there was a 4.7-fold increase in HB-EGF mRNA levels in human gastric cancers compared with normal gastric tissues. There was a concomitant 3.9-fold increase in EGF-R mRNA levels in these cancers. Immunostaining revealed co-localization in 72% of the cancer cells of HB-EGF and EGF-R. AR and BTC moieties were not evident by Northern blot analysis. However, using PCR, both AR and BTC mRNA species were demonstrated in normal and cancerous gastric tissues. By Northern blot analysis, HB-EGF, TGF-alpha, AR, BTC and EGF-R mRNA moieties were co-expressed in KATO III and NCI-N87 gastric cancer cell lines. Furthermore, HB-EGF, EGF and TGF-alpha enhanced the growth of both cell lines in a dose-dependent manner. Our findings suggest that HB-EGF is relatively abundant in human gastric cancers and that co-expression of the EGF ligand family may lead to excessive activation of EGF-R in this disorder.

Adenocarcinoma↗
PubMed1996

Gastric microcirculatory changes during gastric tube formation: assessment with laser Doppler flowmetry.

Poor perfusion of the gastric substitute in esophageal replacement frequently causes anastomotic break down. In this in vivo study we assessed gastric microperfusion before, during, and after gastric tube formation by means of laser Doppler flowmetry in 11 patients undergoing esophagectomy for esophageal cancer. Baseline blood flux along the greater curvature was 323 +/- 57, 167 +/- 28, and 190 +/- 44 perfusion units (PU) and along the lesser curvature 222 +/- 44 and 227 +/- 46 PU. Blood flux was significantly higher in close proximity to tumor-infiltrated areas (819 +/- 172 and 879 +/- 119 PU, P < 0.03 and P < 0.008 compared to normal stomach). Dissection of the gastrocolic ligament and the left gastric artery reduced gastric blood flux along the greater curvature to 69 +/- 21, 79 +/- 19, and 155 +/- 61 PU. Elongation and transformation of the stomach to a gastric tube further reduced blood flux in the stomach especially at the fundus. In this study laser Doppler flowmetry was a valuable tool to assess microcirculatory changes during gastric tube formation as well as pathological blood flow in tumor bearing areas of the stomach in vivo. Quantification of the perfusion of gastric tubes in esophageal replacement might help prevent ischemia-induced anastomotic breakdown.

Adenocarcinoma↗
PubMed1996

Pancreatic cancer: the potential clinical relevance of alterations in growth factors and their receptors.

Molecular alterations play a key role in the pathogenesis of gastrointestinal cancers. In the present paper we describe relevant molecular alterations in human pancreatic adenocarcinomas. Overexpression of growth factor receptors (EGF receptor, c-erbB2, c-erbB3, TGF beta receptor I-III), growth factors (EGF, TGF alpha, TGF beta-1-3, aFGF, bFGF), adhesion molecules (ICAM-1, ELAM-1) and gene mutations (p53, K-ras, DCC, APC) are present in a significant number of these tumors. These changes stimulate tumor growth and enhance the metastatic behavior of pancreatic cancer cells and thereby may contribute to shorter postoperative survival following tumor resection.

E-Selectin↗
PubMed1996

Importance of the duodenal passage and pouch volume after total gastrectomy and reconstruction with the Ulm pouch: prospective randomized clinical study.

The objective of this randomized study was to examine which reconstruction method and which pouch volume offer the best preconditions for a good quality of life and extensive physiologic regulation of gastrointestinal hormones after total gastrectomy. Up to now there is no general agreement with regard to the ideal reconstruction after total gastrectomy. The importance of the duodenal passage, the need for a pouch reconstruction, and the ideal pouch volume are matters of controversy. A total of 60 patients underwent the following reconstructions: Ulm pouch (pouch reconstruction with preservation of the duodenal passage), Hunt-Lawrence-Rodino pouch, or Roux-en-Y reconstruction without pouch. The clinical course, quality of life, and regulation of gastrointestinal hormones in correlation to reconstruction type and pouch volume were documented. Quality of life was assessed by means of a standardized specific questionnaire. Blood glucose, insulin, cholecystokinin, motilin, secretin, and pancreatic polypeptide were measured after stimulation by a standardized test meal. Six months after total gastrectomy those patients with an Ulm pouch were found to have a significantly better life quality (p < 0.01), higher body weight, and better physiologic regulation of gastrointestinal hormones; moreover, they developed (in contrast to all other reconstruction types) no pathologic glucose tolerance. Our conclusion is that all patients with a postoperative life expectancy of at least 6 months (i.e., tumor stages UICC I and II) should undergo pouch reconstruction with preservation of the duodenal passage.

Aged↗
PubMed1996

Carcinoid of the pancreas: clinical characteristics and morphological features.

The classical carcinoid tumour (WHO) of the pancreas is extremely rare and its diagnosis may puzzle physicians and pathologists. Here, 29 previously published cases of pancreatic carcinoid tumours, including one new case, are reviewed. Literature research was done using MedLine from 1966 to 1995. Pancreatic carcinoids produce an atypical carcinoid syndrome. Skin flushing was reported in only 34%. The main symptom was pain, followed by diarrhoea and weight loss. Elevated urinary 5-HIAA levels were found in 85% (17/20). The immunocytochemical sensitivity for serotonin was 100% (11/11). The diagnosis of pancreatic carcinoid tumour is based on the typical endocrine histological features together with increased serotonin metabolism. Generally, the slow growth rate and late invasion of adjacent organs render local resection possible, but the high incidence of distant metastases (69%) prevents long-term survival in the majority of patients. The possible role of the Octreoscan, a new radionuclide imaging technique, is discussed with regard to this tumour entity.

Carcinoid Tumor↗
PubMed1996

Altered expression of transforming growth factor-beta S in chronic renal rejection.

We examined the altered expression of transforming growth factor-beta s in chronic renal rejection in humans, including transforming growth factor beta-1 (TGF-beta 1), TGF-beta 2, TGF-beta 3 and their receptors, transforming growth factor beta receptor type I (T beta R-I) and T beta R-II. Using Northern blot analysis and immunohistochemistry, 10 specimens of chronically rejected and 8 normal kidney samples were analyzed. By Northern blot analysis the expression of mRNA encoding TGF-beta 1, TGF-beta 2, TGF-beta 3 (P < 0.02), T beta R-I and T beta R-II (P < 0.02) was decreased in chronically rejected renal cortex samples, compared to normal controls. Immunohistochemical analysis of the normal renal cortex showed strong immunostaining for TGF-beta 1 and TGF-beta 3, and mild immunostaining for TGF-beta 2 in the proximal and distal tubulointerstitium, but no signal for any of the TGF-beta isoforms in the glomeruli or in the cortical vessels. In sharp contrast, the glomeruli and the cortical vessels of the rejected kidney specimens exhibited strong immunostaining for TGF-beta 1 and TGF-beta 3, whereas the tubules revealed a decrease in immunoreactivity. T beta RI and T beta RII immunostaining showed similar changes as observed with TGF-beta 1 and TGF-beta 3 antibodies. There was a concomitant increase in B-cell accumulation in the glomeruli, while T-cells and macrophages were diffusely abundant in the rejected samples. Since TGF-beta S are potent inducers of extracellular matrix proteins and have been shown to be involved in fibrotic disease, the increase in TGF-beta 1 and TGF-beta 3 immunoreactivity in the glomeruli suggests that there is a redistribution in TGF-beta expression in chronic renal allograft rejection. Together with changes affected by B-cell mediated immunity, the above alterations might contribute to the histopathological changes that occur in this disorder, such as intimal fibrosis, arteriosclerosis and glomerular and tubular sclerosis.

Chronic Disease↗
PubMed1996

Single-strand conformation polymorphism analysis of the epidermal growth factor receptor at codon 497.

A variant human epidermal growth factor (EGF) receptor (HER) with a transition (G to A) at codon 497, resulting in a substitution of a lysine for an arginine, was recently demonstrated in several human pancreatic cancer cell lines. In the present study, we compared the frequency of expression of wild-type (HER497R) and variant (HER497K) EGF receptors in normal and malignant pancreatic tissue samples using single-strand conformation polymorphism analysis. Both receptors were expressed in normal (42%) and malignant (46%) tissues. Three samples (two normal and one cancer) expressed only HER497K. The cancer sample that was homozygous for HER497K exhibited strong EGF receptor immunoreactivity. The high frequency of HER497K expression suggests that it is due to a relatively common polymorphism in the HER coding region. Its presence in some of the cancer samples suggests that, like the wild-type receptor, HER497K also has a role in pancreatic cancer.

Base Sequence↗
PubMed1996

Age-dependent influence of octreotide on stimulated pancreatic growth in the postnatal period of rats.

OBJECTIVE: To investigate the effect of long-acting octreotide (SMS 201-995) on the plasma growth hormone level in preweaning rats and to study the growth and composition of the exocrine pancreas in these rats after stimulation by caerulein- and camostate-induced endogenous cholecystokinin (CCK). METHODS: Wistar rats of both sexes were treated as littermate pairs in two periods of postnatal age, from days 1 to 11 and from days 11 to 21. To stimulate pancreatic growth, caerulein (3 micrograms/kg subcutaneously three times daily) was given from days 1 to 11, and oral camostate (200 mg/kg given once daily) or CCK-8 (10 micrograms/kg subcutaneously three times daily) was administered from days 11 to 21. Octreotide (6 or 15 micrograms/kg subcutaneously twice daily) was administered alone or in combination with caerulein or camostate. The rats were exsanguinated on days 11 or 21, and each pancreas was removed, weighed and analysed. RESULTS: Caerulein stimulated pancreatic growth and raised the trypsin concentration; camostate induced pancreatic hypertrophy and hyperplasia. By day 11, octreotide had decreased the plasma growth hormone level and the basal pancreatic trypsin concentration and content. Given in combination with caerulein, octreotide reduced the growth hormone level and the stimulated trypsin and DNA contents. By day 21, rats treated with octreotide in the camostate group showed a reduced basal pancreatic trypsin concentration and a decreased basal trypsin content (although the changes were not significant). Plasma growth hormone levels were not significantly reduced. CONCLUSION: The antitrophic pancreatic action of octreotide and its plasma growth hormone-lowering effect were shown in rats during the first 10 days after birth. These effects were less notable from days 11 to 21, a period when CCK receptors increase in number and components of the stimulus-secretion mechanism are mature.

Analysis of Variance↗
PubMed1996

Hyperlipaemia intensifies the course of acute oedematous and acute necrotising pancreatitis in the rat.

BACKGROUND: Serum triglyceride concentrations higher than 10 to 20 mmol/l are probably a risk factor for developing acute pancreatitis in humans. AIMS: To therefore analyse the influence of hyperlipaemia on the course of acute oedematous and acute necrotising pancreatitis in rats. SUBJECTS: Male Wistar rats were used in all experiments. METHODS: Six different groups of animals were used: two groups without pancreatitis (controls), two with acute oedematous pancreatitis, and two with acute necrotising pancreatitis. One group from each pair was treated with Triton WR 1339, which induces endogenous hyperlipaemia. Blood samples were taken from all subjects to measure triglyceride, cholesterol, amylase, and lipase. Pancreatic tissue samples were taken and the degree of pancreatic damage was judged microscopically. RESULTS: In the control groups no significant changes occurred, either in serum enzyme activities or in histology. The hyperlipaemic subgroup of animals with acute oedematous pancreatitis developed significantly higher (p < 0.001) serum amylase activities and a greater degree of histological damage (p < 0.01) than the animals of the non-hyperlipaemic acute oedematous pancreatitis group. In the animals with necrotising pancreatitis, serum lipase activity and the histological degree of pancreatic damage were significantly higher in the hyperlipaemic animals than in the non-hyperlipaemic animals. CONCLUSION: This study shows that hyperlipaemia intensifies the course of acute oedematous and acute necrotising pancreatitis in rats.

Acute Disease↗
PubMed1996

Efficacy of somatostatin and its analogues in pancreatic surgery and pancreatic disorders.

Major pancreatic resection is still accompanied by considerable morbidity (35%) and mortality (10%). Typical complications, such as pancreatic fistula and abscess, are chiefly associated with exocrine pancreatic secretion. The hormone somatostatin and its analogue octreotide are well known as potent inhibitors of exocrine pancreatic secretion. In two randomised, double-blind, placebo-controlled, multicentre trials we assessed the prophylactic effect of the perioperative inhibition of exocrine pancreatic secretion by octreotide to prevent postoperative complications. Each patient received 3 X 100 micrograms/day octreotide or placebo subcutaneously. A significant reduction in fistula, abscess, fluid collection, sepsis and postoperative pancreatitis occurred with patients undergoing pancreatic resection for cancer. Results were similar in a second study, using the same protocol but recruiting only patients with chronic pancreatitis. A new randomised, controlled multicentre trial is also described, in which 300 patients with severe acute pancreatitis are being treated with or without octreotide in double-blind fashion. The results will clarify the influence of inhibition of exocrine pancreatic secretion by octreotide on the course of acute pancreatitis, and hence its potential, through inhibition of digestive enzyme secretion, as a treatment for acute pancreatitis.

Adult↗
PubMed1996

Maldigestion after total gastrectomy is associated with pancreatic insufficiency.

OBJECTIVES: Subsequent to total gastrectomy, many patients develop maldigestion and weight loss. The mechanisms that underlie these changes are not known. Therefore, in a prospective study, we have analyzed endocrine and exocrine pancreatic function in patients before and 3 months after total gastrectomy. METHODS: In 15 patients (12 male, three female, median age 62.4 yr) undergoing total gastrectomy due to gastric cancer, a direct exocrine pancreatic function test (secretin-cerulein test) was performed. In addition, a standard test meal was given to all patients to study endocrine pancreatic function and the pattern of hormones that influence exocrine pancreatic secretion. In nine patients, both function tests were repeated 3 months after total gastrectomy. Before and at 11 points after the application of the test meal, blood samples were taken for the measurement of glucose, insulin, glucagon, gastrin, pancreatic polypeptide, and cholecystokinin. In addition, a secretin-cerulein test was performed to analyze trypsin, chymotrypsin, amylase, bicarbonate, and the juice volume in the duodenal aspirates. RESULTS: Three months after total gastrectomy, all patients exhibited severe primary exocrine pancreatic insufficiency. Secretin-cerulein tests revealed that pancreatic juice secretion, trypsin, chymotrypsin, and amylase were significantly reduced by 76%, 89%, 91%, and 72%, respectively, 3 months after total gastrectomy and secretin and cerulein stimulation. Post-operatively, the patients had a pathological glucose tolerance with increased postprandial insulin and glucagon secretion. The baseline and postprandial gastrin and pancreatic polypeptide secretion were significantly decreased after total gastrectomy. In contrast, early postprandial cholecystokinin secretion was significantly increased postoperatively. CONCLUSIONS: After total gastrectomy, patients develop severe primary exocrine pancreatic insufficiency with decreased gastrin, decreased late postprandial pancreatic polypeptide, and increased cholecystokinin levels. These findings may explain why many patients with total gastrectomy have maldigestion and weight loss postoperatively. Therefore, gastrectomized patients should be given pancreatic enzymes to avoid these symptoms.

Ceruletide↗
PubMed1996

[Surgical therapy in chronic pancreatitis].

In patients with chronic pancreatitis, surgical treatment is required when conservative approaches are unsuccessful in treating symptoms and complications of the disease. The indications for surgery are 1) recurrent abdominal pain which does not respond to analgesics and 2) duodenal, common bile duct and/or main pancreatic duct obstruction or stenosis. In addition, obstruction of the retropancreatic vessels with subsequent portal hypertension is an indication to operate. Over the last decades the surgical standards in the treatment of chronic pancreatitis have changed. Due to disappointing long-term results, pancreatic left resection and drainage procedures of the main pancreatic duct are limited only to a small number of patients. In a number of patients with chronic pancreatitis, inflammatory enlargement of the pancreatic head causes complications which require surgical treatment. In the past, the classical Whipple resection has served as the standard operation in these patients. However, the classical Whipple resection was initially inaugurated for pancreatic head malignancies, and in addition to resection of the pancreatic head it includes resection of the complete duodenum, the extra hepatic bile system and 2/3 of the stomach. The Whipple procedure's disappointing long-term results and especially its disappointing quality of life have led to the development of newer organ-preserving procedures designed to treat complications caused by chronic pancreatitis. The pylorus-preserving Whipple resection is a modification of the classical Whipple resection which avoids the resection of the stomach. Since its initial publication by Watson in 1945 and Traverso and Longmire in 1978, pylorus preserving Whipple resection has been performed by many surgeons for the treatment of chronic pancreatitis. However, the high incidence of postoperative diabetes mellitus following this operation is a major drawback that has limited its use. The duodenum-preserving pancreatic head resection was developed to selectively remove the pancreatic head subtotally by preserving the body and tail of the pancreas as well as the pylorus, the duodenum, and the extrahepatic biliary tract. With this organ-preserving operation all the pancreatic head-related complications of chronic pancreatitis can be abolished without inducing diabetes mellitus. Excellent short- and long-term follow-up results prove the superiority of the duodenum-preserving pancreatic head resection over the classical and the pylorus-preserving Whipple resections in patients with chronic pancreatitis. Therefore, the duodenum-preserving pancreatic head resection should be adopted as a new standard operation in patients with chronic pancreatitis and pancreatic head-related complications.

Chronic Disease↗
PubMed1996

[Prognosis in pancreatic carcinoma].

Pancreatic cancer is one of the most frequent carcinomas of the human gastrointestinal tract. despite considerable progress in diagnosis, its prognosis has remained unchanged during the last years. Up to now, there is no possibility to screen patients for pancreatic carcinomas, and the symptoms of the disease are uncharacteristic and often misleading. Surgical treatment, with resection of the tumor is the only chance for cure, but for experienced pancreatic surgeons, an advanced tumor stage at the time of operation is a common finding. Large studies reveal the poor prognosis of the disease. Only 20-30% of all patients suffering from pancreatic cancer can be operated with curative intention. In 80-85% of all cases, the tumor has spread into peripancreatic lymph nodes. Thus, mean 5-years survival rates of 3 to 5% are commonly reported, and the median survival time after establishment of diagnosis is 4-6 months. Improvements in surgical technique and postoperative patient's care have led to an impressive decrease in the formerly considerable morbidity and mortality after pancreatic resection. If the tumor can be resected at an early stage and the regional lymph nodes are not involved, median 5-years survival rates of 20-40% are commonly reported. Further approaches include more radical surgical procedures with dissection of the entire peripancreatic region and resection of the upper abdominal blood vessels. Whether this new technique or a combination of operation, radiation and chemotherapy will improve the prognosis of the disease remains unclear. Large clinical trials are necessary to prove these assumptions.

Epidermal Growth Factor↗