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Biomedical subjects

H G Beger

Publications and source records attributed to H G Beger.

At least 163 records · Page 9Linked to original sources
PubMed1998

Small carcinoma of the pancreas. Factors of prognostic relevance.

UNLABELLED: Tumor size seems to be one of the primary prognostic factors that influence outcome in pancreatic cancer patients. This finding is reflected in both the Japanese and the International Union against Cancer (UICC) staging systems, in which T categories have a major influence on stage grouping. To investigate whether small tumor size is a prognostic indicator in patients with pancreatic carcinoma, we evaluated (in a prospective study) patients with a small pancreatic cancer, categorized as T1a (<2 cm) or T1b (<4 cm) tumors according to the UICC (1997). PATIENTS AND RESULTS: Of 670 treated patients with pan-creatic malignancies, 26 (3.8%) had a small pancreatic tumor (20 T1b; 6 T1a), Twenty-one patients were treated by pylorus-preserving duodenopancreatectomy, 4 patients re-ceived a left pancreatic resection, and 1 patient underwent a total pancreatectomy. All procedures included extensive soft tissue clearance. Local growth pattern was analyzed according to the Japan Pancreas Society (JPS) criteria for pancreatic cancer, i.e., lymph node involvement - N1 (limited to group 1 nodes) was found in 6/26 patients. Serosal infiltration - S1 (single area) was found in 6/26 and S2 (multiple areas) in 6/26; S3 (infiltration to adjacent organs) was found in 1/26. Retroperitoneal infiltration - Rp1 (adjacent to the pancreas) was found in 7/26 and Rp2 (not limited to adjacent tissues, but no other organs involved) was found in 3/26. Venous involvement (Pv2) was found in 1/26. The 5- and 10-year survival rate for the 26 patients was 46%. Interestingly, the T1a tumor patients had a significantly lower 5 year survival rate than the T1b patients (32% vs 58%; P < 0.05). Of prognostic relevance was lymph node metastasis, and retroperitoneal and serosal involvement and these patients had a significantly lower 5-year survival rate than those without such involvement regardless of tumor size (P < 0. 01). CONCLUSIONS: An overall 5-year survival rate of 46% is exceptionally good. Unfortunately, among pancreatic cancer patients those with a small carcinoma represent a highly selected group, representing less than 5% in our series. Interestingly tumor size is of less prognostic relevance than lymph node, retroperitoneal, and serosal involvement. Radical resection with extensive soft tissue clearance therefore seems essential to achieve such a high survival rate.

Chi-Square Distribution↗
PubMed1998

Carcinoma of the head of the pancreas arising from the uncinate process.

BACKGROUND: Carcinoma located in the uncinate process (CUP) of the pancreatic head is considered to be rare. Exact epidemiological data, however, are not available because the series published so far consist of fewer than ten patients. The purpose of this prospective study was to evaluate the clinical appearance of CUP and to compare findings with those of patients with carcinoma in the ventral aspect of the pancreatic head (VPC), which represents the most frequent localization. RESULTS: Some 39 (8 per cent) of 506 evaluated patients suffered from CUP. Mean age was 63.3 years. The most frequent complaints were upper abdominal pain (n = 32) and weight loss (n = 35). Jaundice was seen in only five patients and was never an early symptom. The level of CA19-9 was raised in 33 patients. The best diagnostic procedure to detect CUP was computed tomography (CT) (sensitivity 93 per cent), whereas endoscopic retrograde cholangiopancreatography was not useful (sensitivity 21 per cent). Vascular involvement was significantly (P < 0.01) more common in CUP (n = 19) than in VPC (48 versus 19 per cent). This finding and the fact that most patients with CUP were diagnosed at a late stage with distant metastasis or severe vascular involvement present (n = 21) are responsible for the significantly lower rate of operation (n = 25) (64 versus 92 per cent, P < 0.05) and the significantly shorter median survival time (5 versus 11 months, P < 0.05). CONCLUSION: Patients with CUP have a poor prognosis as a result of the lack of early symptoms (jaundice) and early vascular involvement due to the proximity of the uncinate process to the mesenteric root. A raised level of CA19-9, together with weight loss and/or upper abdominal pain, should prompt CT.

Abdominal Pain↗
PubMed1998

Genetic alterations in chronic pancreatitis: evidence for early occurrence of p53 but not K-ras mutations.

BACKGROUND: In patients suffering from chronic pancreatitis the risk for the development of pancreatic cancer ranges from 4 to 6 per cent. Various mutations are associated with pancreatic cancer, especially of p53 and K-ras. The incidence of these mutations in resected chronic pancreatitic tissue was investigated. METHODS: In the present study DNA from 80 samples of tissue from patients with chronic pancreatitis was isolated and subjected to single-strand conformation polymorphism (SSCP) analysis of p53 exons 5-9 and restriction fragment length polymorphism analysis of K-ras (codon 12). RESULTS: No mutations in the K-ras gene were detected. On SSCP analysis, eight of 80 cases of chronic pancreatitis showed alterations (two in exon 5, four in exon 6, two in exon 7). DNA sequence analysis revealed one deletion of 21 amino acids (exon 5), four polymorphisms in exon 6 with no change in the amino acid sequence, one point mutation in exon 5, and two point mutations located in the intron between exons 6 and 7. CONCLUSION: These data show that in some cases of chronic pancreatitis mutations in the p53 gene occur without morphological evidence of pancreatic cancer.

Chronic Disease↗
PubMed1998

Role of ultrasonographically guided fine-needle aspiration cytology in the diagnosis of infected pancreatic necrosis.

BACKGROUND: Early detection of infected pancreatic necrosis has a major impact on further management and outcome in acute pancreatitis. The aim of this study was to evaluate the clinical value of ultrasonographically guided fine-needle aspiration cytology (FNAC) in patients with necrotizing pancreatitis over an 8-year period. METHODS: From January 1988 to September 1996 193 (mean 2.0 (range 1-9) aspirations per patient) prospectively assessed FNACs guided ultrasonographically were performed in 98 patients with necrotizing pancreatitis proven by contrast-enhanced computed tomography. Aspirates were considered infected if either Gram stain and/or culture revealed micro-organisms. RESULTS: Ultrasonographically guided FNAC correctly diagnosed infection in 29 of 33 patients with infected necrosis a median of 13 days after onset of symptoms. Of 61 patients with sterile necrosis 55 were identified correctly as sterile by FNAC. There were six false-positive and four false-negative aspirates of which nine occurred during the first week of the disease. In four patients who did not undergo operation FNAC revealed Gram-negative organisms; however, in the absence of repeated aspirations, the positive results remained unconfirmed. An overall sensitivity of 88 per cent and a specificity of 90 per cent was obtained. No difference was found in biochemical and clinical parameters indicating systemic inflammatory response syndrome before each FNAC between patients with proven sterile or infected necrosis. All patients tolerated the procedure well and no major complications were observed. CONCLUSION: Ultrasonographically guided FNAC is a fast and reliable technique for the diagnosis of infected necrosis. As complication rates are very low, the procedure can be repeated at short intervals to improve the diagnostic accuracy. Ultrasonographically guided FNAC is recommended for all patients with necrotizing pancreatitis in whom systemic inflammatory response syndrome persists beyond the first week after onset of symptoms.

Adolescent↗
PubMed1998

Benign tumour of the ampulla of Vater: surgical treatment and prognosis.

OBJECTIVE: To find out whether wide local resection is adequate treatment for patients with benign tumours of the papilla of Vater. DESIGN: Retrospective study. SETTING: University hospital, Germany. SUBJECTS: 31 patients with benign tumours out of a total of 129 with lesions of the ampulla of Vater treated between May 1978 and February 1995. INTERVENTIONS: Histological examination of specimens before, during, and after the operation. MAIN OUTCOME MEASURES: Sensitivity and positive predictive value of histological examination, and outcome of treatment. RESULTS: Histological examination before and during the operation had a sensitivity of 89% and 97%, respectively. 28 patients were treated by wide excision of the ampulla and 3 by pylorus-preserving partial pancreaticoduodenectomy. At a median follow up of 43 months (range 6-156) there was no evidence of recurrent disease. CONCLUSION: Wide excision of the ampulla with reconstruction and reimplantation of the duct is adequate treatment for benign lesions. If the histological picture is uncertain, partial pancreaticoduodenectomy is justified in patients at low risk.

Adolescent↗
PubMed1998

The value of intraoperative laparoscopic examination of the contralateral inguinal ring during hernia repair in children.

Approximately 40% of children with a clinical unilateral inguinal hernia display a patent processus vaginalis on the contralateral side; half of these children subsequently develop an inguinal hernia. The management of this problem is still controversial. Different strategies to identify patients who profit from an open contralateral exploration have been applied (diagnostic pneumoperitoneum, herniography, ultrasound). The purpose of this study was to evaluate the usefulness of intraoperative laparoscopy in a no-puncture technique through the opened hernia sack. In 75 children (age 6 months to 7 years) with clinical unilateral hernia laparoscopy (5-mm Laparoscope, 30 degrees and 70 degrees ), in cases of wide-open contralateral internal inguinal ring (Type III) an open surgical exploration was performed. Twelve patients (17%) fulfilled the laparoscopic criteria of a Type III ring. The diagnose was confirmed during open contralateral exploration. Seven children (8%) showed a patent but small processus vaginalis with a shallow internal ring. These patients were treated conservatively. In the follow-up period (median 6 months) one subsequent hernia developed. There was no technical failure, and no associated complications were seen. The median time for laparoscopy was 6 minutes. Intraoperative laparoscopy during unilateral hernia repair allows the identification of patients who profit from bilateral open surgery during the same operation with little additional operating time, and so far with no resulting complications. Application of this method may avoid a second hospitalization and operation as well as unnecessary routine bilateral open exploration. As an additional source of information through excellent visualization of the abdominal cavity, this method proved helpful to examine the incarcerated bowel after repositioning.

Child↗
PubMed1998

The clinical value of human pancreas-specific protein procarboxypeptidase B as an indicator of necrosis in acute pancreatitis: comparison to CRP and LDH.

Early assessment of severity in acute pancreatitis (AP) has a major impact on further treatment. Previous studies have shown that human pancreas-specific protein (hPASP)/procarboxypeptidase B (PCPB) is a new diagnostic and prognostic marker in AP. In the present study we focused on the prognostic properties of this parameter and analyzed the clinical value of hPASP in discriminating edematous from necrotizing AP. The results were compared to those for C-reactive protein (CRP) and lactate dehydrogenase (LDH). A total of 70 patients was enrolled in this prospective study. Based on contrast-enhanced computed tomography or intraoperative results, 39 patients (27 male, 12 female; median age, 42 years; median Ranson score, 6) suffered from necrotizing pancreatitis (NP) and 31 patients (12 male, 19 female; median age, 57; median Ranson score, 1.5) from acute interstitial-edematous pancreatitis (AIP). Serum concentrations of hPASP/PCPB, CRP, and LDH were measured at 24-h intervals over 14 days after admission by a radioimmunoassay (upper normal value, 60 ng/ ml), a lasernephelometric assay (upper normal value, 4 mg/L), and an enzymekinetic method (upper normal value, 240 U/L), respectively. During the overall observation period concentrations of hPASP/PCPB, CRP, and LDH were significantly higher in patients with NP compared to those with AIP. Based on receiver operating characteristics, the best cutoff levels for predicting NP were >200 ng/ml for hPASP/PCPB, >140 mg/L for CRP, and >290 U/L for LDH. Discrimination between AIP and NP was best on day 3 for both hPASP/PCPB (sensitivity, 91%; specificity, 64%; accuracy, 79%) and CRP (sensitivity, 83%; specificity, 84%; accuracy, 83%) and on day 5 of AP for LDH (sensitivity, 88%; specificity, 100%; accuracy, 91%). The overall accuracy in differentiating AIP from NP within the first 4 days after onset of symptoms was 74% for hPASP/PCPB, 75% for CRP, and 76% for LDH. None of the parameters correlated with the extent of necrosis or the etiology of AP. hPASP/PCPB provides good discrimination between AIP and NP at an early stage of the disease, with results comparable to those for CRP and LDH. Although hPASP/PCPB is both disease specific and predictive for necrosis, the clinical use of this test in its present form is limited due to drawbacks in terms of test performance and cost factors.

Adolescent↗
PubMed1998

Increased cyclin D1 expression in chronic pancreatitis.

Cyclin D1 is an important regulator of the G1 phase of the cell cycle. In this study we examined the expression and localization of cyclin D1 in chronic pancreatitis (CP), a condition associated with fibrosis, acinar cell degeneration, and foci of duct cell proliferation. Northern blotting of total RNA from the normal pancreas and from the pancreas of patients with CP revealed the presence of a 4.4-kb cyclin D1 mRNA transcript in all samples. Densitometric analysis indicated that pancreatic cyclin D1 mRNA levels were 2.0-fold increased in CP compared to normal controls (p = 0.0046). In the normal pancreas, faint cyclin D1 immunoreactivity was present in the nuclei and cytoplasm of some ductal cells and islet cells. In contrast, in CP, moderate to strong cyclin D1 immunoreactivity was present in many ductal and islet cells, as well as in some acinar cells and fibroblasts. These findings raise the possibility that enhanced cyclin D1 expression may contribute to a hyperproliferative state in CP.

Adult↗
PubMed1998

Role of fibroblast growth factors and their receptors in pancreatic cancer and chronic pancreatitis.

The fibroblast growth factor (FGF) family is a group of homologous heparin-binding polypeptides that has been implicated in a variety of human neoplasms and presently includes 14 members. FGF signaling is mediated by a dual-receptor system, consisting of four high-affinity tyrosine kinase receptors, termed fibroblast growth factor receptors (FGFRs), and of low-affinity heparan sulfate proteoglycan receptors that enhance ligand presentation to the FGFRs. Several FGFs, including FGF-1, -2, -3, -4, -5, -6, and -7, and several FGFR variants, among them the 2 immunoglobulin-like form and the IIIc splice variant of FGFR-1 and the keratinocyte growth factor receptor, a splice variant of FGFR-2, are expressed in human pancreatic cancer cell lines and are overexpressed in human pancreatic cancers or in the pancreas of chronic pancreatitis and, therefore, may play important roles in the pathobiology of these pancreatic diseases. This review summarizes the current information on the involvement of the FGF family and their receptors in human pancreatic cancer and chronic pancreatitis.

Chronic Disease↗
PubMed1998

Secretory phospholipase A2 in patients with infected pancreatic necroses in acute pancreatitis.

Secretory synovial-type PLA2 (sPLA2-II) in peripheral blood is known to be associated with systemic complications in patients with severe diseases. Being the pacemaking enzyme in eicosanoid synthesis, sPLA2-II is a mediator of the inflammatory response and plays a role in host defense against bacterial infection. We evaluated the clinical role of systemic sPLA2-II in bacterial infection of pancreatic necroses in severe acute pancreatitis. In 58 patients with acute pancreatitis, pancreatic and sPLA2-I and sPLA2-II were measured daily for the first 14 days of hospital treatment by a time-resolved fluoroimmunoassay. All 36 patients with necrotizing pancreatitis underwent regular fine needle aspiration (FNA) to monitor bacterial infection. In 10 patients, infected necroses were found on FNA and postoperative examination. On admission and at most days throughout the observation period, systemic sPLA2-II was significantly higher in patients with infected necroses than in patients with sterile necroses or interstitial pancreatitis. This difference was not found for sPLA2-I, but values were higher in necrotizing pancreatitis than in interstitial pancreatitis at the first 2 days of hospital treatment. If sPLA2-II was >300 ng/ml on 2 successive days within the first 4 days, infected necroses could be predicted with a sensitivity of 89%, a specificity of 88%, and a negative predictive value of 95%. Systemic sPLA2-II has the potential to identify patients at risk of bacterial infection of pancreatic necroses and its routine measurement may therefore, in combination with FNA, offer a valuable tool in monitoring patients with acute necrotizing pancreatitis.

Acute Disease↗
PubMed1998

Endotoxin binding and elimination by monocytes: secretion of soluble CD14 represents an inducible mechanism counteracting reduced expression of membrane CD14 in patients with sepsis and in a patient with paroxysmal nocturnal hemoglobinuria.

Little is known about the role of peripheral blood mononuclear cells (PBMCs) in lipopolysaccharide (LPS) elimination. We studied the endotoxin elimination capacities (EEC) of PBMCs of 15 healthy volunteers, 13 patients with sepsis, and 1 patient suffering from paroxysmal nocturnal hemoglobinuria (PNH). Although expression of CD14, the best-characterized receptor for LPS to date, was reduced from 93.6% +/- 0.8% in healthy subjects to 50.5% +/- 6.5% in patients with sepsis and was 0.3% in a patient with septic PNH, EEC were found to be unchanged. There was no difference in the amount of tumor necrosis factor alpha (TNF-alpha) released by PBMCs of healthy donors and patients with sepsis. Anti-CD14 antibodies (MEM-18) completely suppressed EEC, binding of fluorescein isothiocyanate-labeled LPS to monocytes as determined by FACScan analysis, and TNF-alpha release in all three groups studied. The concentrations of soluble CD14 (sCD14) secreted by endotoxin-stimulated PBMCs from healthy donors and patients with sepsis amounted to 4.5 +/- 0.4 and 20.1 +/- 1.8 ng/ml, respectively. Based on our results, we suggest that PBMCs eliminate LPS by at least two different mechanisms; in healthy subjects, the membrane CD14 (mCD14) receptor is the most important factor for LPS elimination, while in patients with sepsis (including the septic state of PNH), increased sCD14 participates in LPS elimination. Secretion of sCD14 is strongly enhanced under conditions of low expression of mCD14 in order to counteract the reduction of mCD14 and maintain the function of monocytes. This sCD14 may substitute the role of mCD14 in LPS elimination during sepsis. The elimination of LPS by PBMCs correlates with the binding reaction and the secretion of TNF-alpha.

Adult↗
PubMed1998

Enhanced fibroblast growth factor 5 expression in stromal and exocrine elements of the pancreas in chronic pancreatitis.

BACKGROUND: Fibroblast growth factor 5 (FGF-5) belongs to a group of mitogenic and angiogenic heparin binding growth factors but its potential role in chronic inflammatory conditions is not known. AIMS: To compare FGF-5 expression in the normal pancreas and in the pancreas of patients with chronic pancreatitis (CP) and to characterise FGF-5 expression and secretion in TAKA-1 cells, an immortalised Syrian hamster pancreatic duct cell line. METHODS AND RESULTS: Northern blotting revealed the presence of a 4.0 kb FGF-5 mRNA transcript in both normal and CP tissue samples. Densitometric analysis indicated that the transcript levels were increased by a factor of 1.44 in CP tissue samples compared with normal tissue samples (p = 0.039). By immunohistochemisty and in situ hybridisation, FGF-5 was faintly expressed in ductal and islet cells in the normal pancreas. In contrast, in CP tissue samples, there was abundant expression of FGF-5 in ductal, acinar, and islet cells, as well as in periductal fibroblasts. FGF-5 was also expressed in TAKA-1 cells as determined by Northern blotting. By immunoblotting of heparinsepharose precipitates, TAKA-1 cells were shown to secrete FGF-5 into the medium. CONCLUSION: Exocrine and stromal derived FGF-5 has the potential to participate in autocrine and paracrine pathways that may contribute to the pathobiology of chronic pancreatitis.

Adult↗
PubMed1998

K-ras mutations at codon 12 are rare events in chronic pancreatitis.

BACKGROUND/AIMS: The activation of the K-ras gene at codon 12 is thought to be an early genetic event in the multistep pathogenesis of pancreatic cancer. Since the risk of pancreatic cancer is significantly elevated in subjects with chronic pancreatitis, the aim of the present study was to determine the frequency of K-ras mutations in chronic pancreatitis. METHODS: Pancreatic DNA from intraoperatively resected tissues of 60 patients with chronic pancreatitis and 11 patients with histologically confirmed pancreatic carcinoma was evaluated by PCR amplification and restriction fragment length polymorphism analysis. RESULTS: In none of the 60 samples of chronic pancreatitis could K-ras mutations be identified using two independent PCR assays. In 5 of 11 patients with pancreatic carcinoma, K-ras mutations in codon 12 were detected. CONCLUSION: These data indicate that K-ras mutations are rare events in chronic pancreatitis. Alternatively, it is possible that the time span between the occurrence of K-ras mutations and malignant transformation is rather short.

Carcinoma↗
PubMed1998

[Prognostic value of molecular biologogy and immunologic parameters in human pancreatic carcinoma].

In the present study we investigated the prognostic relevance of molecular and immunological changes in pancreatic carcinoma. 82 tissue specimens of adenocarcinoma of the pancreas were stained immunohistochemically with following factors: p53, p21WAF1, Cyklin D, EGF, EGF-R, cERB-B2, CD95, BCL-2 and Cathepsin D. We further determined the serum levels of sCD44, sCD44v6, neopterin and IL-2R. Except Cyclin D none of the immunohistochemically determined factors had prognostic significance. Interestingly all of the immunological serum parameters were of high prognostic significance. These data demonstrate the prognostic relevance of immunological parameters in human adenocarcinoma of the pancreas and could raise the possibility of an early immunological intervention in pancreatic cancer.

Adenocarcinoma↗
PubMed1998

[Nitrogen monoxide and oxygen radicals work contrarily on proliferation behavior of human fibroblasts].

Oxygen radicals and nitric oxide are involved in a variety of regulative processes especially with regard to inflammation, immunoregulation and regulation of the vascular tone. The aim of our study was to investigate the effects of both these highly reactive molecules on the proliferation of human fibroblasts. We therefore cultured WI38 cells under various culture conditions like exposure to oxygen radicals and endogenously produced as well as exogenously applied nitric oxide. Exposure of WI38 to oxygen radicals led to a reduction of cell proliferation. Similarly induction of endogenous nitric oxide production by cytokines induced an inhibition in cell proliferation. Interestingly exogenously applied nitric oxide increased proliferation rates of WI38 cells. These data could point to a functional role of oxygen radicals and nitric oxide in the regulation of fibroblast growth.

Apoptosis↗
PubMed1998

[Effect of cellular growth factors on hepatocytes in experimental infection--regulation of NF-kappa B and glutathione homeostasis].

Infections, sepsis and trauma lead to cellular damage of different degrees. The formation of nitrogen and reactive oxygen intermediates (NOI and ROI) play a central role in cellular damage. In addition, it is well established that the intracellular GSH content can control both radical species whereas GSH levels are controlled by the presence of cellular growth factors. The aim of the following study was to investigate the ROI and nitric oxide formation depending on the GSH levels and the presence or absence of hepatocellular growth factors. In addition, we investigated their effects on hepatocellular injury and the status of activation of the nuclear transcriptional factor NF-kappa B which is influenced by various radical forms and the cellular GSH contents. Our data clearly demonstrate that hepatocellular growth factors such as EGF and TGF alpha can increase the GSH contents and the NOx production. In addition, we found a reduction of cellular injury and NF-kappa B expression when hepatocytes were preincubated with growth factors. Taken together, we conclude that growth factors are able to protect against hepatocellular injury in experimental sepsis by increasing the cellular GSH contents either to reduce superoxide anion formation or to induce increased NO synthesis activity with subsequent increased NO production.

Cells, Cultured↗
PubMed1998

[Membrane injuries of pancreatic acinar cells are the first changes in early stage acute experimental pancreatitis].

We tested the hypothesis that membrane wounding of acinar cells is one of the earliest changes during the induction of acute pancreatitis. Wounding of cell membranes was detected by the penetration of the animals own albumin into cells. The pancreatitis was induced by the intraperitoneal injection of supramaximal doses of caerulein. The controls received saline. Fifteen to 180 min. after the injection the animals were perfused with buffer followed by fixative. Frozen sections of pancreas were processed identically for immunocytological localization of albumin. The intensity of staining was quantified by image analysis. Animals receiving caerulein consistently display significantly greater (p < 0.001) anti-albumin immunostaining in the cytoplasm of acinar cells than controls. The penetration of albumin into acinar cells indicates that wounding of their plasma membrane occurs during the onset of acute pancreatitis. Wounding of membranes may allow the exit of molecules such as enzymes from the acinar cells during this period.

Acute Disease↗