[Adjuvant chemotherapy and/or radiotherapy in stomach carcinoma: what makes sense?].
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Adenocarcinoma↗
Biomedical subjects
H Friess
Publications and source records attributed to H Friess.
[Chronic pancreatitis with inflammatory enlargement of the pancreatic head].
A number of patients with chronic pancreatitis develop an inflammatory enlargement of the head of the pancreas leading to complications such as common bile duct, duodenal, pancreatic duct, and/or vascular obstruction. The duodenum preserving pancreatic head resection has been developed to treat these lesions and to avoid a Whipple procedure in chronic pancreatitis. Between 1972 and 1992 280 patients (231 male, 49 female, mean age 44, range 22-76 years) underwent a duodenum preserving pancreatic head resection for chronic pancreatitis. The indication to operate was a cholestases syndrome in 50% of the patients, a duodenal compression in 36% and an obstruction of the portal vein in 16% of the patients. 94% suffered from pain, 53% had recurrent severe pain attacks and 72% had daily pain. Hospital mortality was 1.1% (3/280). Pancreatic fistula, leakage of pancreatic anastomosis and postoperative bleeding occurred in 4.6%, 1.8% and 3.2% of the patients, respectively. A relaparotomy needed 16 patients (5.7%). With respect to glucose tolerance in the early postoperative period 88% of the patients, showed no change in comparison with the preoperative glucose tolerance analysis. In a long-term follow-up (mean follow-up time was 3.7 years (3 months to 18 years)) 219 patients were included. The late mortality within the follow-up period was 5.0% (11/219). 90% of the patients had no or rare pain in the long-term follow-up. 63% of the patients were full rehabilitated professionally. The duodenum preserving pancreatic head resection represents a new standard procedure which solves most surgical problems in chronic pancreatitis. It does not lead to diabetes mellitus.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Enhanced erbB-3 expression in human pancreatic cancer correlates with tumor progression.
The erbB-3 gene encodes a transmembrane protein that is related to the epidermal growth factor (EGF) receptor and erbB-2. We compared erbB-3 expression in the normal human pancreas, human pancreatic carcinomas, and cultured human pancreatic cancer cell lines. Northern blot analysis of total RNA revealed the anticipated 6.2-kb mRNA transcript in all 19 normal pancreatic samples. In 17 of 27 pancreatic cancers, there was a 6.7-fold increase (P < 0.001) in erbB-3 mRNA levels. Southern blot analysis did not reveal erbB-3 gene amplification. Four of six pancreatic cancer cell lines exhibited the 6.2-kb erbB-3 mRNA transcript, and all four cell lines coexpressed the epidermal growth factor receptor and erbB-2. Using a highly specific antibody, we determined that faint to moderate erbB-3 immunoreactivity was present in the ductal cells in the normal pancreas. In 47% (27/58) of the pancreatic cancers, there were many cancer cells with intense erbB-3 immunostaining. The presence of erbB-3 in the cancer cells was associated with advanced tumor stage and shorter survival postoperatively. These data indicate that a significant proportion of human pancreatic cancers overexpress erbB-3, and that erbB-3 may contribute to disease progression in this disorder.
Adenocarcinoma↗
Coexpression of the c-met proto-oncogene and hepatocyte growth factor in human pancreatic cancer.
The c-met proto-oncogene encodes a transmembrane tyrosine kinase receptor (MET) that has the capacity to modulate cell proliferation and differentiation; it is activated by the hepatocyte growth factor. Using a highly specific anti-MET antibody we found mild MET immunoreactivity in acinar, ductal, and islet cells in the normal human pancreas and intense MET immunoreactivity in many of the duct-like cancer cells in 14 of 16 human pancreatic adenocarcinomas. Intense MET immunoreactivity was also evident in the ductal cells in regions adjacent to the cancer cells. Northern blot analysis of total RNA revealed that, by comparison with the normal pancreas, pancreatic cancers exhibited a 7-fold (P < 0.01) increase in c-met mRNA levels. Hepatocyte growth factor mRNA levels were increased 10-fold (P < 0.05) in the same cancers. The concomitant over-expression of c-met and hepatocyte growth factor in human pancreatic cancers suggests that there is excessive activation of c-met-dependent signaling pathways that may contribute to pancreatic cancer cell growth in vivo.
Adolescent↗
Induction and expression of heparin-binding EGF-like growth factor in human pancreatic cancer.
Heparin-binding EGF-like growth factor (HB-EGF) is a polypeptide with an apparent molecular weight of 22 kilodalton that is related to epidermal growth factor (EGF) and that binds and activates the EGF receptor. We examined HB-EGF biological action and expression in human pancreatic cancer cell lines, and compared HB-EGF expression in normal and cancerous pancreatic tissues. HB-EGF enhanced the growth of human pancreatic cancer cells in a dose-dependent manner. Several cell lines expressed HB-EGF mRNA transcripts, and the transcript level was enhanced by HB-EGF, as well as by 12-O-tetradecanoylphorbol-13-acetate and transforming growth factor-alpha (TGF-alpha). By comparison with the normal pancreas, HB-EGF mRNA levels were increased in human pancreatic cancer tissues. These findings suggest that HB-EGF may participate in aberrant autocrine and paracrine activation of the EGF receptor, thereby contributing to pancreatic cancer cell growth.
Blotting, Northern↗
Induction and expression of amphiregulin in human pancreatic cancer.
The epidermal growth factor receptor is activated by a family of polypeptides that includes the growth factor amphiregullin (AR). Using Northern blot analysis and the polymerase chain reaction, we now report that AR mRNA is expressed in human pancreatic cancer cell lines, and that this expression is enhanced in several of these cell lines by tetradecanoyl phorbol acetate and transforming growth factor alpha. AR was also expressed in normal and malignant pancreatic tissues. However, in the normal pancreas, AR immunostaining was most evident in the nuclei of ductal cells. In contrast, in many carcinomas, AR was also present in the cytoplasm of the ductal-like cancer cells. Cytoplasmic localization of AR was associated with a more advanced clinical stage. These findings suggest that AR may contribute to aberrant activation of the epidermal growth factor receptor in human pancreatic cancer, and may enhance disease progression.
Amino Acid Sequence↗
Carcinoid of the ampulla of Vater. Clinical characteristics and morphologic features.
BACKGROUND: Carcinoid tumors of the gastrointestinal tract are most common localized in the appendix, followed by the small intestine, the rectum, and the stomach. The localization of these tumors at the ampulla of Vater is extremely seldom. METHODS: In the present study the authors describe two patients with carcinoid tumors of the ampulla Vater and review 71 previously published cases. RESULTS: Most patients presented with jaundice, but without carcinoid syndrome. Because the tumor grows submucosally, preoperative diagnosis was correct only in 15%. Most tumors were around 2 cm in size. Metastasis to lymph nodes and/or liver was present in 45%. Standard treatment is Whipple resection or local excision in small tumors. CONCLUSIONS: Carcinoid tumors of the ampulla of Vater are an extremely rare clinical entity. Generally, the prognosis is good with a 5-year survival period of 90%.
Adult↗
Cripto, a member of the epidermal growth factor family, is over-expressed in human pancreatic cancer and chronic pancreatitis.
Cripto is a 188 amino-acid protein containing a central segment that shares amino-acid sequence homology with epidermal growth factor (EGF) and transforming growth factor alpha (TGF-alpha). The EGF receptor, EGF and TGF-alpha are expressed in the normal human pancreas, and are over-expressed in human pancreatic cancer. Therefore, in the present study we sought to determine whether cripto is found in the normal human pancreas and whether its expression is altered in pancreatic cancer. Because chronic pancreatitis (CP) is associated with interstitial fibrosis similar to that observed in pancreatic cancer, we also examined cripto expression in pancreatic tissues from patients with CP. In the normal pancreas, cripto immunoreactivity was found at moderate levels in most ductal cells and was present very faintly in a rare acinar cell. In 26 of 58 pancreatic cancers, cripto immunoreactivity was present in many cancer cells. Its presence was associated with advanced tumor stage, but not with shorter post-operative survival. Cripto was also present in acinar and ductal cells adjacent to the cancer cells, and in many ductal atrophic acinar cells in the CP samples. Northern blot analysis revealed a marked increase in cripto mRNA levels in the cancer and CP samples. By densitometry, there was a 11- and 4-fold increase in cripto mRNA levels in pancreatic cancer and CP respectively. Southern blot analysis did not reveal an increase in gene copies encoding cripto either in cancer or in CP. These findings indicate that cripto expression may contribute to disease progression in pancreatic cancer, and implicate cripto in the histopathological alterations that occur in the pancreas both in cancer and in CP.
Adolescent↗
Differential expression of heat shock proteins in pancreatic carcinoma.
In the present study we sought to determine by Northern blot analysis and mRNA in situ hybridization whether gene expression of heat shock proteins (HSPs) (HSP 89 alpha, HSP 89 beta, HSP 70, and ubiquitin) is altered in pancreatic carcinoma, compared to control tissues (normal pancreas and chronic pancreatitis tissue). HSP 89 alpha was selectively overexpressed in pancreatic carcinoma, and tumor cells were shown to contain the largest amount of HSP 89 alpha mRNA. Steady state levels of HSP 70 mRNA were increased in pancreatic carcinoma (tumor and connective tissue cells) and in chronic pancreatitis (connective tissue cells and residues of exocrine acinar cells). HSP 89 beta and ubiquitin B were constitutively expressed at high levels in pancreatic tissue from all three groups; HSP 89 beta mRNA was found in cells of parenchymal and stromal origin. A strong correlation was found between the expression of HSP 70 and the expression of transforming growth factor beta 1. The finding that HSPs are differentially expressed in pancreatic cancer, compared to normal pancreas and chronic pancreatitis tissue, and the cancer specificity of HSP 89 alpha suggest that HSPs play a specific role in the pathogenesis of pancreatic cancer, e.g., by participating in regulatory processes or in tumor immunity, as proposed previously.
Blotting, Northern↗
A subgroup of patients with chronic pancreatitis overexpress the c-erb B-2 protooncogene.
OBJECTIVE: Chronic pancreatitis (CP) is a chronic condition associated with pancreatic fibrosis. A small subgroup of patients with CP develop enlargement of the head of the pancreas (EHP). This study examined some of the mechanisms that may lead to the development of EHP. SUMMARY BACKGROUND: The c-erb B-2 protooncogene encodes a 185-kDa transmembrane growth factor receptor (p185) that regulates cell growth and differentiation. METHODS: The authors analyzed c-erb B-2 expression in samples obtained from the head of the pancreas from 26 patients with CP (5 women, 21 men) using immunohistochemical and molecular technique. A diagnosis of CP with EHP was made when the vertical pancreatic head diameter was greater than 4 cm (14 patients), as determined by contrast-enhanced computed axial tomography scan. Pancreatic tissues from 15 healthy organ donors served as control subjects. RESULTS: In all patients without EHP and in the healthy control subjects, p185 immunoreactivity was present at low levels. In contrast, strong p185 immunoreactivity was observed in acinar and ductal cells in all patients with EHP. By in situ hybridization, c-erb B-2 messenger ribonucleic acid (mRNA) grains were expressed at high levels in patients with CP with EHP in both ductal and acinar cells. Northern blot analysis demonstrated a 4.5-fold increase (p < 0.001) in c-erb B-2 mRNA levels in patients with EHP compared with patients without EHP and healthy control subjects. Southern blot analysis did not reveal c-erb B-2 gene amplification or rearrangement. CONCLUSIONS: These findings indicate the c-erb B-2 is not overexpressed in most patients with CP. However, its overexpression in patients with CP with EHP suggest that c-erb B-2 may contribute to the pathophysiologic processes that lead to pancreatic head enlargement.
Adolescent↗
Alcohol does not affect the trophic pancreatic effect of CCK and its plasma level in young rats.
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Animals↗
Pseudolymphoma of the pancreas mimicking cancer.
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Aged↗
Chronic pancreatitis is associated with increased concentrations of epidermal growth factor receptor, transforming growth factor alpha, and phospholipase C gamma.
The epidermal growth factor (EGF) receptor is a transmembrane protein that binds EGF and transforming growth factor alpha (TGF alpha), and that stimulates phospholipase C gamma 1 (PLC gamma 1) activity. In this study the role of the EGF receptor in chronic pancreatitis was studied. By immunohistochemistry, the EGF receptor, TGF alpha, and PLC gamma 1 were found to be expressed at high concentrations in pancreatic ductal and acinar cells from chronic pancreatitis patients. Northern blot analysis showed that, by comparison with normal controls, 19 of 27 chronic pancreatitis tissues exhibited a 5.7-fold increase in EGF receptor mRNA concentrations, and 20 of 27 chronic pancreatitis tissues exhibited a sixfold increase in TGF alpha mRNA concentrations. In situ hybridisation confirmed that overexpression occurred in ductal and acinar cells, and showed that both mRNA moieties colocalised with their respective proteins. These findings suggest that TGF alpha may act through autocrine and paracrine mechanisms to excessively activate the overexpressed EGF receptor in the two major cell types of the exocrine pancreas, thereby contributing to the pathobiology of this disorder.
Adult↗
Role of somatostatin and its analogues in the treatment of acute and chronic pancreatitis.
Acute pancreatitis is caused by the activation of digestive enzymes in the pancreas and a possible treatment, therefore, is the inhibition of enzyme secretion. This approach is somewhat controversial, however, as it is not clear whether pancreatic secretion continues to occur during the course of acute pancreatitis. Animal studies show an appreciable reduction of secretion in the inflamed pancreas, but studies in humans are not conclusive. The use of somatostatin or its analogue, octreotide, has been investigated in several clinical studies. A meta analysis of six individual studies in which somatostatin was given for acute pancreatitis showed that somatostatin significantly reduces mortality. A trial in patients with moderate to severe acute pancreatitis showed a lower rate (although not statistically significant) of complications in patients treated with 3 x 200 and 3 x 500 micrograms/day octreotide, compared with controls and patients receiving a lower dose of octreotide. A further study showed a significant reduction in patient controlled analgesics in patients treated with octreotide compared with controls. Pain is the important clinical symptom of chronic pancreatitis, possibly resulting from an increased intraductal pressure during secretion. The effect on pain of the inhibition of pancreatic secretion by octreotide has been investigated in two studies. One showed no significant reduction in pain after treatment with octreotide for three days. In the other, in which octreotide was used for three weeks, significantly less pain and analgesic use was recorded during octreotide treatment than during placebo. The most common complication of chronic pancreatitis is the formation of pseudocysts. There is some evidence that octreotide may be useful in their treatment.
Acute Disease↗
Inhibition of pancreatic secretion under long-term octreotide treatment in humans.
The somatostatin analogue octreotide (SMS 201-995) is a potent inhibitor of human exocrine pancreatic secretion. In the present study we analyzed the effect of octreotide (3 x 100 micrograms, daily) given over a time period of 7 days on hormone-stimulated exocrine pancreatic secretion in 6 healthy volunteers using a secretin-ceruletide test. The secretin-ceruletide test was carried out before, following the first injection of octreotide (day 1) and after a 7-day treatment with 3 x 100 micrograms octreotide daily. Duodenal fluid was collected over 30 min without stimulation, over 60 min following a bolus injection of 1 U/kg body weight secretin, and over 60 min during a continuous infusion of secretin and ceruletide. Following the first injection of octreotide and following 7 days of octreotide treatment secretin/ceruletide-stimulated amylase secretion was significantly reduced. Trypsin and chymotrypsin secretion was significantly reduced after the first injection of octreotide when pancreatic secretion was stimulated by secretin and ceruletide simultaneously. However, secretin and ceruletide-induced trypsin and chymotrypsin secretion was not inhibited after 7 days of octreotide treatment. Baseline, secretin and secretin/ceruletide-stimulated bicarbonate output were not influenced by octreotide either following the first injection of octreotide or the 7 days' treatment. Octreotide is a potent inhibitor of secretin/ceruletide-stimulated pancreatic amylase, trypsin and chymotrypsin secretion. However, following a 7-day treatment with octreotide this inhibition is only persistent for pancreatic amylase secretion.
Adult↗
Potential role of somatostatin and octreotide in the management of acute pancreatitis.
The pathophysiology of acute pancreatitis remains controversial. Activation of digestive enzymes in the pancreas may play an important role in the course of this disease. Therefore, the inhibition of enzyme secretion may be a possible treatment concept. However, it is not clear whether pancreatic secretion continues during the course of acute pancreatitis. In the present paper experimental and clinical studies are reviewed to evaluate the effect of somatostatin and octreotide treatment in acute pancreatitis.
Acute Disease↗
Octreotide in the treatment of acute pancreatitis: results of a unicenter prospective trial with three different octreotide dosages.
Acute necrotizing pancreatitis is still associated with high morbidity and mortality. In this prospective clinical trial, we analyzed the effect of octreotide in patients with acute pancreatitis. Eight patients received either 3 x 100, 3 x 200 or 3 x 500 micrograms octreotide subcutaneously per day over a period of 10 days. The complication rate was lower in the group of patients who received 3 x 200 or 3 x 500 micrograms octreotide than in the control group and the group of patients who received the dosis of 3 x 100 micrograms octreotide per day. The results of this study are promising and must be validated in a controlled clinical trial with octreotide in a larger patient population.
Acute Disease↗
Role of octreotide in the treatment of pancreatic cancer.
Prognosis in patients with advanced pancreatic cancer is dismal. There has been no effective therapy for these patients so far. Somatostatin and its analogues have been proven to be potent inhibitors of experimental pancreatic cancer. Tumor inhibition is supposed to be mediated directly by somatostatin-binding sites or indirectly by suppression of growth factors. In two trials the value of the new somatostatin analogue octreotide in a low-dose (3 x 100 micrograms/day) and a high-dose (3 x 2,000 micrograms/day) protocol was evaluated in patients with advanced pancreatic cancer. Median survival of the patients with a low-dose protocol was 3 months. However, the treatment of pancreatic cancer with a high-dose protocol revealed a median survival of 6 months and stable disease in 4/10 patients. According to quality of life scoring 4 patients showed values comparable to healthy controls. Octreotide therapy with a high-dose protocol is a promising experimental therapeutic approach to advanced pancreatic cancer.
Female↗