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Biomedical subjects

J Kleeff

Publications and source records attributed to J Kleeff.

At least 73 records · Page 4Linked to original sources
PubMed1999

Stable transfection of a glypican-1 antisense construct decreases tumorigenicity in PANC-1 pancreatic carcinoma cells.

Glypican-1 belongs to a family of glycosylphosphatidylinositol (GPI)-anchored heparan sulfate proteoglycans (HSPGs) that affect cell growth, invasion, and adhesion. Cell-surface HSPGs are believed to act as co-receptors for heparin-binding mitogenic growth factors. It was reported that glypican-1 is strongly expressed in human pancreatic cancer, and that it may play an essential role in regulating growth-factor responsiveness in pancreatic carcinoma cells. In this study we investigated the effects of decreased glypican-1 expression in PANC-1 pancreatic cancer cells. To this end, PANC-1 cells were stable transfected with a full-length glypican-1 antisense construct. The glypican- antisense transfected clones displayed markedly reduced glypican- protein levels and a marked attenuation of the mitogenic responses to heparin-binding growth factors that are commonly overexpressed in pancreatic cancer: fibroblast growth factor-2 (FGF2), heparin-binding epidermal growth factor (EGF)-like growth factor (HB-EGF), and hepatocyte growth factor (HGF). In addition, glypican-1 antisense-expressing PANC-1 cells exhibited a significantly reduced ability to form tumors in nude mice in comparison with parental and sham-transfected PANC-1 cells. These data suggest that glypican-1 plays an important role in the responses of pancreatic cancer cells to heparin-binding growth factors, and documents for the first time that its expression may enhance tumorigenic potential in vivo.

Animals↗
PubMed1999

Enhanced expression of the type II transforming growth factor-beta receptor is associated with decreased survival in human pancreatic cancer.

Transforming growth factor-betas (TGF-betas) bind to the type II TGF-beta receptor (TbetaRII), which then heterodimerizes with the type I TGF-beta receptor (TbetaRI), thereby initiating a signaling cascade. TGF-betas are overexpressed in pancreatic cancer, and this overexpression is associated with more aggressive disease. Although TbetaRII also is overexpressed in pancreatic ductal adenocarcinoma cells in vivo, the biologic significance of this overexpression is not completely known. Therefore in this study, we characterized TbetaRII expression by Northern blot analysis in 32 normal and 42 cancerous pancreatic tissues and correlated the survival of the cancer patients with TbetaRII messenger RNA (mRNA) levels. Northern blot analysis revealed that, by comparison with the normal controls, TbetaRII expression was increased in 19 (45%) of 42 cancer samples. Densitometric analysis of all the pancreatic tissues revealed a 3.4-fold increase (p < 0.01) in TbetaRII mRNA levels in the cancer tissues by comparison with normal controls. There was a strong correlation between the expression of TbetaRII and the levels of two invasion-promoting genes, plasminogen-activator-inhibitor-1 (PAI-1) and matrix-metalloproteinase-9 (MMP9). Log-rank analysis of the Kaplan-Meier survival curves indicated that patients whose tumors overexpressed TbetaRII had a significantly shorter survival period than did patients whose cancers expressed low levels of TbetaRII. It is suggested that TbetaRII overexpression may be a marker that correlates with disease progression in pancreatic ductal adenocarcinoma.

Adolescent↗
PubMed1999

Molecular aspects of pancreatic cancer and future perspectives.

Pancreatic cancer has one of the worst prognoses of all human malignancies and the molecular mechanisms underlying this aggressive disease have been extensively investigated in the past years. Tyrosine kinase growth factor receptors and their ligands act to influence tumor cell growth, differentiation, invasion, metastasis, and angiogenesis. In pancreatic cancer a variety of these growth factor receptors and ligands are expressed at increased levels and this overexpression influences the clinical course of the disease. For example, the concomitant presence of the EGF receptor and its ligands EGF, TGF-alpha, and/or amphiregulin is associated with enhanced tumor aggressiveness and shorter survival periods following tumor resection. Furthermore, the growth inhibitory effects of the TGF-beta superfamily of serine-threonine kinase receptors and their ligands are often blocked in pancreatic cancer cells. In addition to these alterations, mutations of the p53 tumor-suppressor gene, the K-ras proto-oncogene, and the Smad4 gene are frequently present in these tumors. Taken together, the abundance of growth-promoting factors, the disturbance of growth inhibitory pathways, and the presence of gene mutations combine to give pancreatic cancer cells a distinct growth advantage which clinically results in rapid tumor progression and poor survival.

ErbB Receptors↗
PubMed1999

Prevention and treatment of complications in pancreatic cancer surgery.

Pancreatic cancer is the fourth leading cause of death from malignant disease in Western industrialized countries. It is a devastating disease with a very poor prognosis and has a death rate roughly equal to its incidence rate. As this tumor is resistant to all medical treatment options, such as radio- and chemotherapy, radical surgical resection is the only chance of cure so far. Significant advances have been made over the past decades in pancreaticoduodenectomy, which is the standard operation in patients with pancreatic head cancer or periampullary cancer. In specialized centers the operative mortality has fallen under 5%. However, the postoperative complication rates after this demanding procedure are still between 30 and 40%. Complications are mainly due to the technical difficulty of performing a safe and proper anastomosis between the stomach or small bowel and the soft pancreas. This article reviews the treatment of the complications most frequently occurring after pancreatic cancer surgery, such as leakage of pancreatic anastomosis, pancreatic fistula, abscess and hemorrhage. Furthermore, we discuss the management of these complications and how complications following pancreatic surgery can be prevented.

Abdominal Abscess↗
PubMed1999

Characterization of cytokeratin 20 expression in pancreatic and colorectal cancer.

Cytokeratin 20 belongs to the epithelial subgroup of the intermediate filament family. Because of its restricted range of expression in humans, it has become an important tool for detecting and identifying metastatic cancer cells by immunohistochemistry and by PCR analysis. Despite its widespread diagnostic use in colorectal cancer and occasional use in pancreatic cancer, little is known about the expression of CK 20 in these tumors in vivo. Therefore, in the present study we characterized CK 20 expression in pancreatic and colorectal cancer by comparison with its expression in the normal pancreas and colon. Tissue samples from 24 patients with pancreatic cancer and from 41 patients with colorectal cancer were examined for CK 20 expression by Northern blot analysis, immunohistochemistry, and in situ hybridization. CK 20 expression was observed in the cancer cells of both cancer types. A subgroup of the pancreatic cancers exhibited a 3.2-fold increase in CK 20 mRNA by comparison with respective normal controls. In contrast, colon cancers underexpressed CK 20 mRNA by comparison with the respective controls. In the normal tissues, CK 20 immunoreactivity was relatively faint and sparse in the pancreatic ductal cells but intense and abundant in the apical portions of the colonic mucosa. CK 20 immunoreactivity was also evident in the ductal cells from the chronic pancreatitis-like lesions adjacent to the cancer cells. Furthermore, distant metastases from pancreas carcinomas exhibited strong CK 20 immunoreactivity. It is concluded that CK 20 is overexpressed in pancreatic cancer and that it can serve as an excellent marker for metastatic pancreatic cancer.

Colorectal Neoplasms↗
PubMed1998

The cell-surface heparan sulfate proteoglycan glypican-1 regulates growth factor action in pancreatic carcinoma cells and is overexpressed in human pancreatic cancer.

Heparan sulfate proteoglycans (HSPGs) play diverse roles in cell recognition, growth, and adhesion. In vitro studies suggest that cell-surface HSPGs act as coreceptors for heparin-binding mitogenic growth factors. Here we show that the glycosylphosphatidylinositol- (GPI-) anchored HSPG glypican-1 is strongly expressed in human pancreatic cancer, both by the cancer cells and the adjacent fibroblasts, whereas expression of glypican-1 is low in the normal pancreas and in chronic pancreatitis. Treatment of two pancreatic cancer cell lines, which express glypican-1, with the enzyme phosphoinositide-specific phospholipase-C (PI-PLC) abrogated their mitogenic responses to two heparin-binding growth factors that are commonly overexpressed in pancreatic cancer: fibroblast growth factor 2 (FGF2) and heparin-binding EGF-like growth factor (HB-EGF). PI-PLC did not alter the response to the non-heparin-binding growth factors EGF and IGF-1. Stable expression of a form of glypican-1 engineered to possess a transmembrane domain instead of a GPI anchor conferred resistance to the inhibitory effects of PI-PLC on growth factor responsiveness. Furthermore, transfection of a glypican-1 antisense construct attenuated glypican-1 protein levels and the mitogenic response to FGF2 and HB-EGF. We propose that glypican-1 plays an essential role in the responses of pancreatic cancer cells to certain mitogenic stimuli, that it is relatively unique in relation to other HSPGs, and that its expression by pancreatic cancer cells may be of importance in the pathobiology of this disorder.

Adolescent↗
PubMed1998

Transfection of the type I TGF-beta receptor restores TGF-beta responsiveness in pancreatic cancer.

Transforming growth factor-beta (TGF-beta) signaling is initiated following heterodimerization of the type II TGF-beta receptor (TbetaRII) with the type I TGF-beta receptor (TbetaRI). Both receptors are required for TGF-beta responsiveness. In the present study, we characterized the actions of TGF-beta1 in T3M4 human pancreatic cancer cells, which express low levels of TbetaRI and high levels of TbetaRII. Cells were transiently transfected with p3TP-Lux, a TGF-beta-responsive luciferase reporter gene construct. TGF-beta1 was without effect in parental T3M4 cells, but caused a time- and dose-dependent increase in luciferase activity in T3M4 cells co-transfected with a TbetaRI cDNA expression vector. Co-transfection of TbetaRI with a truncated Smad4 cDNA that is known to block TGF-beta-dependent signaling, abrogated the TbetaRI-induced increase in luciferase activity. Sequencing of the TbetaRI and the Smad4 genes in T3M4 cells did not reveal any mutations. These findings indicate that one mechanism for TGF-beta resistance in pancreatic cancer is due to a quantitative decrease in TbetaRI expression.

Activin Receptors, Type I↗
PubMed1998

Concomitant over-expression of activin/inhibin beta subunits and their receptors in human pancreatic cancer.

Activins and inhibins belong to the transforming growth factor-beta (TGF-beta) superfamily of multifunctional cytokines that bind to transmembrane receptors with serine/threonine kinase activity. In this study, we characterized the levels of expression of 3 activin/inhibin subunits (betaA, betaB, alpha), and 2 type I and type II activin receptors (actRI/Ib, actRII/IIb) in pancreatic cancer cell lines and in human pancreatic tissues. In addition, we assessed the growth responsiveness to activin A in these cell lines. All 6 cell lines (ASPC-1, CAPAN-1, COLO-357, MIA-PaCa-2, PANC-1 and T3M4) expressed the activin/inhibin betaA subunit, whereas expression levels of the activin/inhibin betaB and alpha subunits were undetectable. Furthermore, actRI, actRII and actRIIb were expressed in all cell lines and actRIb mRNA was evident in ASPC-1, CAPAN-1, COLO-357 and PANC-1 cells. CAPAN-I and COLO-357 cells were growth-stimulated by activin A in the presence of 10% serum, whereas the other cell lines were resistant to activin A. In contrast, in serum-free medium activin A inhibited the growth of CAPAN-1, COLO-357 and MIA-PaCa-2 cells. Pancreatic cancer samples markedly over-expressed the activin/inhibin betaA subunit, whereas the betaB subunit was only moderately increased in comparison to normal pancreatic samples. Pancreatic cancer tissues also markedly over-expressed actRI, actRIb and actRII. By in situ hybridization, activin/inhibin betaA, actRI, actRIb and actRII were strongly expressed in diffuse infiltrative and duct-like cancer cells. Both the ligand and its receptors were often co-expressed in these cells. Together, our findings suggest that activin A may participate in autocrine activation of pancreatic cancer cells in vivo.

Activin Receptors↗
PubMed1998

The helix-loop-helix protein Id2 is overexpressed in human pancreatic cancer.

Id2 belongs to the Id family of helix-loop-helix (HLH) proteins, which upon heterodimerization with basic HLH proteins prevent basic HLH proteins from DNA binding. Proteins of the Id family act as negative regulatory transcriptional factors, and their expression correlates with cell proliferation and arrested differentiation in many cell lineages. In this study, we characterized the expression of Id2 in normal and cancerous pancreatic tissues. Pancreatic cancers markedly overexpressed Id2 mRNA in comparison to the normal pancreas. Furthermore, there was abundant Id2 immunoreactivity in the cancer cells within the pancreatic tumor mass. In PANC-1 human pancreatic cancer cells, steady-state Id2 mRNA levels increased upon serum addition and decreased after induction of differentiation with either sodium butyrate or 12-O-tetradecanoylphorbol-13-acetate. Inhibition of Id2 expression with Id2 antisense oligonucleotides inhibited the growth of these cells, whereas random and sense oligonucleotides were without effect. These findings suggest that Id2 may have a role in human pancreatic cancer.

Adolescent↗
PubMed1998

Up-regulation of transforming growth factor (TGF)-beta receptors by TGF-beta1 in COLO-357 cells.

In the present study we investigated the actions of transforming growth factor (TGF)-beta1 on gene induction and cyclin-dependent kinase inhibitors in relation to TGF-beta receptor modulation in COLO-357 pancreatic cancer cells. TGF-beta1 inhibited the growth of COLO-357 cells in a time- and dose-dependent manner and caused a rapid but transient increase in plasminogen activator inhibitor-I and insulin-like growth factor binding protein-3 mRNA levels. TGF-beta1 caused a delayed but sustained increase in the protein levels of the cyclin-dependent kinase inhibitors p15(Ink4B), p21(Cip1), and p27(Kip1) and a sustained increase in type I and II TGF-beta receptors (TbetaRI and TbetaRII) mRNA and protein levels. The protein synthesis inhibitor cycloheximide (10 microg/ml) completely blocked the TGF-beta1-mediated increase in TbetaRI and TbetaRII expression. Furthermore, a nuclear runoff transcription assay revealed that the increase in receptor mRNA levels was due to newly transcribed RNA. There was a significant increase in TbetaRI and TbetaRII mRNA levels in confluent cells in comparison to subconfluent (</=80% confluent) controls, as well as in serum- starved cells when compared with cells incubated in medium containing 10% fetal bovine serum. COLO-357 cells expressed a normal SMAD4 gene as determined by Northern blot analysis and sequencing. These results indicate that TGF-beta1 modulates a variety of functions in COLO-357 cells and up-regulates TGF-beta receptor expression via a transcriptional mechanism, which has the potential to maximize TGF-beta1-dependent antiproliferative responses.

Animals↗
PubMed1998

Adaptation of the human pancreas to inhibition of luminal proteolytic activity.

BACKGROUND & AIMS: Feedback regulation of pancreatic enzyme secretion is well established in animals, and their pancreases are able to adapt to intraduodenal inhibition of pancreatic enzymes by proteinase inhibitors such as Camostate (FOY-305; Schwarz GmbH, Monheim, Germany). In this study, we addressed whether similar adaptive changes occur in the human pancreas after 4 weeks of 2 g/day Camostate application. METHODS: Before, at the end of, and 2 weeks after 4-week Camostate treatment (four times 500 mg daily), pancreatic changes were analyzed with the use of a secretin-cerulein test, a test-meal stimulation, cholecystokinin plasma measurement, and standardized ultrasonographic investigations of the pancreas. RESULTS: Duodenal trypsin output after secretion stimulation was significantly increased (+44%; P < 0.01) and duodenal bicarbonate output decreased 22% (P < 0.05) after 4 weeks of Camostate application. The size of the pancreatic head (vertical) increased 8% (P < 0.05) at week 4 and decreased to pretreatment values 2 weeks after treatment (week 6). The other three diameters measured (head oblique, body, and tail) showed a similar pattern. Stimulated cholecystokinin plasma levels 15 minutes after application of a standard test meal increased 62% (P < 0.05). CONCLUSIONS: The human pancreas adapts to oral application of the proteinase inhibitor Camostate. These findings support the theory that feedback control of the exocrine pancreas operates in humans.

Adaptation, Physiological↗
PubMed1998

The role of diagnostic laparoscopy in pancreatic and periampullary malignancies.

BACKGROUND: The role of diagnostic laparoscopy before laparotomy in patients with pancreatic or periampullary malignancies remains controversial. We analyzed the value of using diagnostic laparoscopy to avoid laparotomy in these patients. STUDY DESIGN: Between November 1993 and December 1996, 254 patients with pancreatic or periampullary malignancies were treated. In 74 patients, multiple distant metastases precluded further surgical treatment. In all, 180 patients underwent laparotomy for pancreatic cancer (119 patients) or periampullary cancer (61 patients). Preoperatively, all patients underwent computed tomography for staging and to assess resectability of the tumor. Based on the results of the imaging procedure, the patients were scheduled for either tumor resection or a palliative operation. RESULTS: Twenty-one of 180 patients (12%) with pancreatic or periampullary malignancies were scheduled preoperatively for nonresectional operations because of distant metastasis or retroperitoneal tumor infiltration. In none of these patients was the operative strategy changed. In 159 of 180 patients (88%), a pancreatic resection was planned preoperatively; 119 patients underwent pancreatic resection. In the remaining 40 patients preoperatively scheduled for tumor resection, removal of the tumor was not possible. In 24, this resulted from tumor infiltration into the retropancreatic vessels, and in 16 it resulted from liver or peritoneal metastasis detected for the first time intraoperatively. These 16 patients (10%) could have benefited from diagnostic laparoscopy. Similar results were found in the subgroup of 119 patients with pancreatic cancer, of whom 102 were planned for tumor resection and 17 for palliative operation. Of the 102 patients planned preoperatively for tumor resection, 71 patients (70%) underwent pancreatic resection. In the remaining 31 patients scheduled for tumor resection, removal of the tumor was not possible: in 17 because of tumor infiltration into the retropancreatic vessels and in 14 because of liver or peritoneal metastasis detected for the first time intraoperatively. These 14 patients (14%) also would have benefited from laparoscopy. CONCLUSIONS: Preoperative computed tomography is a reliable technique to detect tumor metastasis in patients with pancreatic or periampullary cancer. Unlike other investigators, we found that only 10% of patients with periampullary or pancreatic cancer and 14% of patients with pancreatic cancer might profit from laparoscopy. Because of this low number, laparoscopy cannot generally be recommended for patients with pancreatic or periampullary cancer before laparotomy.

Adult↗
PubMed1998

Influence of high-dose pancreatic enzyme treatment on pancreatic function in healthy volunteers.

CONCLUSIONS: Adaptive changes in exocrine and endocrine pancreatic function, as well as changes in pancreas size and morphology, were not observed after 4-wk of oral pancreatic enzyme application. These findings suggest that the normal pancreas does not significantly adapt--either morphologically or functionally--to a 4-wk oral application of high-dose pancreatic enzymes. BACKGROUND: The control of exocrine pancreatic enzyme secretion is not completely understood. Although it has been established that exocrine pancreatic secretion is mainly regulated in the short-term by the amount of pancreatic enzymes in the proximal small intestine, it is not known whether long-term application of pancreatic enzymes causes changes in exocrine pancreatic secretion in humans. METHODS: Twelve healthy male volunteers (median age 27 yr) participated in a prospective, randomized, placebo-controlled, double-blind study. Six were placed in the treatment group and six in the placebo group. Over a 4-wk period, the six subjects in the treatment group took 18 capsules of Panzytrat (20,000 units of lipase, 18,000 units of amylase, and 1000 units of protease per capsule) daily. Before (wk 0), 4 wk following pancreatic enzyme application and 2 wk afterward, a secretin-cerulein test was carried out in all subjects to study exocrine pancreatic function (trypsin, chymotrypsin, bicarbonate content, and total pancreatic fluid secretion in the duodenum). One day following the secretin-cerulein test, a standard test meal was given to all subjects to analyze endocrine pancreatic function. Additionally, before starting the treatment, once per week during treatment and 2 wk afterward, an ultrasound examination of the pancreas was carried out to see whether there was any change in pancreas size and morphology. RESULTS: Trypsin content in the duodenal aspirates following simultaneous stimulation with secretin and cerulein after 4 wk of high-dose pancreatic enzyme application was 92% in the treatment group and 82% in the placebo group compared with the wk 0 test results (100%). Two weeks after enzyme application, the secretin/cerulein-stimulated trypsin content was 88% in the treatment group and 107% in the placebo group. None of these changes was statistically significant. The same results were seen for chymotrypsin content, amylase, and bicarbonate content as well as for total pancreatic fluid secretion. Additionally, no change in the endocrine pancreatic function could be observed after 4 wk of pancreatic enzyme treatment. Pancreas ultrasonography revealed no alteration in pancreas size or parenchymal structure during the 4 wk of treatment and the following 2 wk.

Adaptation, Physiological↗
PubMed1998

The plasminogen activator/plasmin system is up-regulated after acute necrotizing pancreatitis in human beings.

BACKGROUND: Proteolysis and formation of new extracellular matrix components are important mechanisms in tissue remodeling and repair. In this study we analyzed the expression and distribution of the urokinase plasminogen activator (uPA), its membrane receptor (urokinase plasminogen activator receptor [uPAR]), and its inhibitor (plasminogen activator inhibitor-1 [PAI-1]) in acute necrotizing pancreatitis in human beings. In addition, we studied the concomitant expression of transforming growth factor-beta-1 (TGF-beta 1), which is activated by uPA from its precursor and is a potent regulator and stimulator of formation of extracellular matrix. METHODS: With immunohistochemistry and Northern blot analysis, the expression and cellular distribution of uPA, uPAR, PAI-1, and TGF-beta 1 were determined in 12 normal pancreata obtained from organ donors and 12 pancreatic tissues obtained from patients undergoing operation because of complications of acute necrotizing pancreatitis. RESULTS: Northern blot analysis showed enhanced expression of uPA, uPAR, and PAI-1 in eight of 12, seven of 12, and nine of 12 necrotizing pancreatitis samples, respectively, compared with normal control samples. In addition, increased TGF-beta 1 mRNA expression was present in eight of 12 necrotizing pancreatitis samples. In contrast, amylase mRNA expression was markedly decreased in the samples of acute necrotizing pancreatitis. Immunohistochemistry revealed elevated uPA, uPAR, and PAI-1 immunoreactivity in the remaining acinar and ductal cells adjacent to the necrotic tissue areas. In contrast, acinar and ductal cells that were located farther from pancreatic necrosis exhibited less uPA and uPAR immunoreactivity. A similar staining pattern in samples of necrotizing pancreatitis was found for TGF-beta 1. CONCLUSIONS: Up-regulation of uPA and uPAR, which activate proteolysis, might create a milieu that enhances lysis and removal of pancreatic necrosis. The increase in TGF-beta 1 might result from the enhanced catalytic conversion of its precursors by uPA, which subsequently might stimulate formation of extracellular matrix, formation of granulation tissue, and fibrosis.

Adolescent↗
PubMed1998

[Transforming growth factor-beta controls pathogenesis of Crohn disease].

The pathogenetic mechanisms which contribute to the progression of Crohn's disease are still not known. Transforming growth factor-beta (TGF-beta) and its subtypes are multifunctional polypeptides which regulate immunological processes as well as the synthesis of the extracellular matrix and fibrogenesis. In the present study, Crohn's disease tissue samples of 18 patients undergoing intestinal resection were analyzed by Northern blot analysis, in situ hybridization and immunostaining for TGF-beta 1-3 and the TGF-beta receptors type I-III (T beta R-I, T beta R-II, T beta R-III). There was a marked overexpression of TGF-beta 1, TGF-beta 3 and T beta R-II in 94% of the Crohn's disease tissue samples. TGF-beta 2 and T beta R-I ALK5 and T beta R-III were enhanced in 72%, 72% and 82% of the Crohn tissue samples, respectively. In situ hybridization and immunostaining revealed that there was frequent coexpression of TGF-beta with its signaling receptors. Our data indicate that TGF-beta and their receptors seem to be involved in the pathogenesis of Crohn's disease. Their enhanced expression might contribute to the increase in extracellular matrix resulting in fibrosis and subsequently in intestinal obstruction.

Adolescent↗
PubMed1997

Gastric emptying following pylorus-preserving Whipple and duodenum-preserving pancreatic head resection in patients with chronic pancreatitis.

BACKGROUND: After pylorus-preserving Whipple (PPW), delayed gastric emptying (DGE) is reported in up to 50% of these patients. We analyzed gastric emptying and hormonal adaptation of cholecystokinin (CCK), pancreatic polypeptide (PP), and gastrin following two surgical procedures for chronic pancreatitis (CP): the PPW and the duodenum-preserving pancreatic head resection (DPPHR). METHODS: Ten patients underwent DPPHR and 10 underwent PPW for CP. Preoperatively and 10 days and 6 months postoperatively, gastric emptying (paracetamol absorption test) and CCK, gastrin, and PP were measured using a test meal stimulation. RESULTS: The area under the serum paracetamol time curve for 0 to 120 minutes (AUC) showed no preoperative difference. Ten days postoperatively, the AUC was significantly reduced (P <0.05) after PPW but not after DPPHR. Six months postoperatively, AUC was comparable with the preoperative findings in DPPHR and PPW. The integrated 180-minute PP release was significantly reduced 10 days and 6 months postoperatively in both groups. The integrated 180-minute CCK release was decreased 10 days after PPW, but failed to be significant (P = 0.053). Gastrin levels were postoperatively unchanged. CONCLUSION: Following DPPHR we found no delay in gastric emptying. In contrast, DGE occurs early after PPW. Our data may help explain the slower recovery in PPW patients with regard to weight gain and relief from pain, which may be due to the functional alteration of gastric emptying and motility after this type of surgery.

Acetaminophen↗
PubMed1997

Molecular versus conventional markers in pancreatic cancer.

Diagnosing and monitoring pancreatic cancer is an ongoing challenge. Conventional markers such as tumor-associated antigens might be supplemented by molecular markers such as gene mutations and growth factor/growth factor receptor alterations in the future. Tumor-associated antigens can easily be measured by different EIA/ELISA systems, but the analysis of gene mutations, growth factors and their receptors requires advanced molecular techniques. CA 19-9 is the most widely used conventional marker for pancreatic cancer and is a useful tool in the diagnosis and follow-up of patients after tumor resection. Nonetheless, its role in detecting early pancreatic cancer is limited. The detection of K-ras and p53 mutations, which occur in about 90 and 50% of pancreatic cancers, respectively, in blood, stool, or bile samples, seems to be a promising approach in the diagnosis. Growth factor and growth factor receptor alterations are often associated with increased tumor aggressiveness and shorter survival following tumor resection. To date the analysis of growth factors/growth factor receptors in pancreatic cancer has not entered clinical use, but further molecular characterization of pancreatic cancer is necessary for earlier and more accurate diagnosis and it may result in new treatment options.

Biomarkers, Tumor↗