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Biomedical subjects

H G Beger

Publications and source records attributed to H G Beger.

At least 91 records · Page 5Linked to original sources

Coexpression of FAS and FAS-ligand in chronic pancreatitis: correlation with apoptosis.

Activation of the Fas receptor by Fas-ligand (FasL) results in apoptosis, and dysregulation of this pathway may contribute to abnormal cell proliferation and cell death. The aim of this study was to compare the expression of Fas and FasL in the normal pancreas and chronic pancreatitis (CP). By Northern blotting, Fas messenger RNA (mRNA) levels were increased in CP in comparison to the normal pancreas. Immunostaining revealed that faint Fas and FasL immunoreactivity was present in ductal and islet cells of the normal pancreas. In CP, there was faint Fas and strong FasL immunoreactivity in the proliferating ductal cells. Additionally, many of these ductal cells in the CP samples exhibited an apoptotic signal, as determined by DNA 3'-OH end labeling. These findings suggest that activation of apoptosis through the Fas receptor may contribute to the pathobiology of CP.

Adult↗

Inflammatory mediators in human acute pancreatitis: clinical and pathophysiological implications.

BACKGROUND: The time course and relationship between circulating and local cytokine concentrations, pancreatic inflammation, and organ dysfunction in acute pancreatitis are largely unknown. PATIENTS AND METHODS: In a prospective clinical study, we measured the proinflammatory cytokines interleukin (IL)-1 beta, IL-6 and IL-8, the anti-inflammatory cytokine IL-10, interleukin 1 beta receptor antagonist (IL-1RA), and the soluble IL-2 receptor (sIL-2R), and correlated our findings with organ and systemic complications in acute pancreatitis. In 51 patients with acute pancreatitis admitted within 72 hours after the onset of symptoms, these parameters were measured daily for seven days. In addition, 33 aspirates from ascites and the lesser sac were measured. RESULTS: Sixteen patients had mild acute pancreatitis (AP) and 35 severe AP (Atlanta classification); 18 patients developed systemic complications requiring treatment. All mediators were increased in AP. sIL-2R, IL-10, and IL-6 were significantly elevated in patients with distant organ failure. An imbalance in IL-1 beta/IL-1RA was found in severe AP and pulmonary failure. Peak serum sIL-2R predicted lethal outcome and IL-1RA was an early marker of severity. IL-6 was the best prognostic parameter for pulmonary failure. CONCLUSION: Our results suggest that local mediator release, with a probable IL-1 beta-IL-1RA imbalance in severe cases, is followed by the systemic appearance of pro- and anti-inflammatory mediators. The pattern of local and systemic mediators in complicated AP suggests a role for systemic lymphocyte activation (triggered by local release of mediators) in distant organ complications in severe AP.

Acute Disease↗

Local and systemic zymogen activation in human acute pancreatitis.

BACKGROUND: Activation of trypsinogen and phospholipase A(2) is an early event in pancreatic inflammation, but little is known about zymogen activation and the severity of human pancreatitis. METHODS: Using a new fluoroimmunoassay we measured trypsinogen activation peptide (TAP) and phospholipase A(2) activation peptide (PROP) in plasma and ascites in 25 patients with acute pancreatitis. TAP, PROP, Pro-PROP and pancreatic PLA(2)-I were measured in plasma for 14 days and in pancreatic necroses, ascitic fluid and pleural effusions. RESULTS: All 16 patients with severe acute pancreatitis (SAP) had pancreatic necrosis, 10 developed systemic complications like sepsis, pulmonary or renal failure, 6 had infected necrosis, and 4 died. All 9 patients with mild pancreatitis (MAP) survived. Plasma TAP on admission was higher in patients with SAP than in those with MAP and increased in infected necroses. It did not correlate with systemic complications. Systemic PROP was not increased in complicated courses but was significantly higher in patients with MAP than in those with SAP on admission. Pro-PROP was higher in patients with SAP than in those with MAP but was not correlated with systemic complications. Plasma pancreatic PLA(2)-I was increased but not different in patients with SAP and those with MAP. In patients with pancreatic necrosis, TAP and PROP were highest, while in those with post-acute pancreatic abscess, only PROP and Pro-PROP were high. In patients with pleural effusion, TAP was low and PROP/ Pro-PROP were high. CONCLUSION: Trypsinogen and PLA(2)-I activation are early events in acute pancreatitis and the activation peptides can be detected in plasma. In the pancreas, trypsinogen activation is accompanied by PLA(2)-I activation in patients with pancreatic necrosis. However, in our study, organ complications in SAP patients was not associated with increased plasma PROP.

Acute Disease↗

Ampullary but not periampullary duodenal diverticula are an etiologic factor for chronic pancreatitis.

BACKGROUND: Duodenal diverticula are common incidental findings. Although a definite treatment is rarely required, an association with biliary and pancreatic diseases is often suggested. Our aim was to determine the frequency of complications in relation to the location of the diverticulum. METHODS: We reviewed 64 patients with extraluminal duodenal diverticula. In 24 of these patients the diverticulum was treated surgically. The incidence of symptoms and complications is analyzed and follow-up in 88% of operated patients is presented. RESULTS: Thirty-one patients presented with ampullary, 36 patients with periampullary diverticula. Three patients had both types of diverticula. The indication for surgery in 24 patients was chronic pancreatitis (n = 12), chronic pain (n = 6), diverticular perforation (n = 3), bleeding (n = 2), or jaundice (n = 1). In 7 out of 31 patients with ampullary and none out of 36 patients with periampullary diverticula, chronic pancreatitis was considered to be induced by the diverticulum. Morbidity in 24 operated patients was 17%, no patient died. At follow-up all patients were free of symptoms. CONCLUSION: Extraluminal duodenal diverticula are frequently found. They rarely cause symptoms and need no surgical treatment. While ampullary duodenal diverticula can cause chronic pancreatitis, periampullary duodenal diverticula are no etiologic factor.

Adult↗

Prospective comparison of endoscopic ultrasound and endoscopic retrograde cholangiopancreatography in the preoperative assessment of masses in the pancreatic head.

AIMS: To compare the diagnostic value of endoscopic ultrasound (EUS) and endoscopic retrograde cholangiopancreatography (ERCP) in the differentiation of malignant from benign masses in the pancreatic head. METHODS: Within 14 months 95 prospective patients with masses in the pancreatic head were assigned for preoperative EUS and ERCP. Both procedures were performed and recorded according to a standardized protocol. Based on intraoperative findings and histology, 50 patients (53%) suffered from malignant and 45 patients (47%) from benign (inflammatory) tumors. RESULTS: Success rates were 96% for EUS and 95% for ERCP. The overall results for EUS and ERCP to predict malignant masses were, respectively: sensitivity 78 and 81%, specificity 93 and 88%, positive predictive value 93 and 89%, negative predictive value 78 and 80%, and diagnostic accuracy 85 and 84%. When EUS and ERCP were taken together, the sensitivity was 92% (specificity 85%), but the diagnostic accuracy (89%) was not significantly enhanced. The results for EUS to diagnose lymph node metastases preoperatively were: sensitivity 55%, specificity 91%, positive predictive value 69%, negative predictive value 84%, and accuracy 81%. CONCLUSIONS: EUS and ERCP have similar diagnostic accuracies to separate malignant from benign masses in the pancreatic head. Combination of both procedures is not superior to the use of one modality alone. Abnormal lymph nodes visualized on EUS in patients with inflammatory masses in the pancreatic head due to chronic pancreatitis should be interpreted cautiously.

Adult↗

Biliary and gastric bypass or stenting in nonresectable periampullary cancer: analysis on the basis of controlled trials.

BACKGROUND: The median survival rate of patients with nonresectable periampullary cancer is not much longer than 6-12 mo. Nevertheless, in most incurable patients palliative treatment is necessary, which has to focus on jaundice, pain, and prevention of gastric outlet obstruction. Up to now, debate remains about how to best provide palliative treatment. METHOD: The results of controlled clinical trials and large multicenter studies comparing operative biliary bypass and biliary stent insertion in nonresectable pancreatic tumors are discussed in this review. RESULTS: The initial success rate in palliation of jaundice is similar after endoscopic stent insertion and biliary bypass operation (range: 90-95 %). Morbidity (range: 1 1-36% vs 26-40%) and 30-d mortality (range: 8-20% vs 15-31%) is higher after bypass operation, whereas stent insertion is accompanied by a higher rate of hospital readmission and reintervention because of recurrent jaundice (range: 28-43%) and a later gastric outlet obstruction (up to 17%). CONCLUSION: Endoscopic biliary stent insertion should be performed if there is evidence of hepatic, peritoneal, or pulmonary metastasis formation, in old patients with a high comorbidity, or if the patient has had several laparotomies. Combined biliary and gastric operative bypass procedures should be performed in nonresectable periampullary carcinomas with accompanying gastric outlet obstruction, in the absence of metastatic spread, if a locally advanced tumor is the only reason for incurability, if exploratory laparotomy demonstrates an unresectable tumor, or if endoscopic treatment fails.

Ampulla of Vater↗

The role of polymorphonuclear leukocytes and oxygen-derived free radicals in experimental acute pancreatitis: mediators of local destruction and activators of inflammation.

Using a retrograde infusion sodium taurocholate pancreatitis model in the rat treatment with oxygen radical scavengers or monoclonal anti-ICAM-1 antibody decreased tissue damage and polymorphonuclear leukocytes (PMN) infiltration. Scavengers or anti-ICAM-1 treatment attenuated the activating capacity of blood PMNs following zymosan stimulation. The local production of oxygen free radicals in the pancreas by systemic infusion of hypoxanthine and regional infusion of xanthine oxidase did not induce acute pancreatitis, although an increase of infiltrating PMNs was observed. Our data suggest that oxygen free radicals and infiltrating PMNs aggravate acute pancreatitis and that both are important mediators of local destruction and systemic activation of PMNs.

Acute Disease↗

Inhibition of epidermal growth factor-induced interleukin-1beta-converting enzyme expression reduces proliferation in the pancreatic carcinoma cell line AsPC-1.

It is suggested that interleukin-1beta-converting enzyme (ICE) and ICE-related proteases play an important role in programmed cell death (apoptosis). We investigated ICE expression in the human pancreatic carcinoma cell line AsPC-1 after stimulation with epidermal growth factor and found a time-dependent expression of active ICE induced by epidermal growth factor. Interestingly, ICE expression does not lead to apoptosis. Cell cycle analyses revealed that acetyl-Tyr-Val-Ala-Asp-chloromethylketone-specific and acetyl-Ala-Ala-Val-Ala-Leu-Leu-Pro-Ala-Val-Leu-Leu-Ala-Leu-Leu-Ala-Pro-T yr-Val-Ala-Asp-aldehyde-specific cell-permeable inhibitors of ICE significantly reduced the proliferation of AsPC-1 cells, which suggested a positive influence of ICE on the proliferation in human pancreatic carcinoma cells.

Apoptosis↗

Inhibition of cyclin D1 expression in human pancreatic cancer cells is associated with increased chemosensitivity and decreased expression of multiple chemoresistance genes.

Cyclin D1 belongs to a family of protein kinases that have been implicated in cell cycle regulation. Inhibition of cyclin D1 expression has been recently shown (M. Kornmann, et al., J. Clin. Invest, 101: 344-352, 1998) to suppress pancreatic cancer cell growth and increase cytotoxic actions of cisplatinum. The aim of the present study was to determine whether inhibition of cyclin D1 expression also modulates the effects of other antineoplastic drugs and whether it is associated with alterations in the level of expression of drug resistance genes. The suppression of cyclin D1 expression after the stable transfection of a cyclin D1 antisense construct in PANC-1 and COLO-357 human pancreatic cancer cells resulted in a significant increase in sensitivity to the fluoropyrimidines 5-fluorouracil and 5-fluoro-2'-deoxyuridine and to mitoxantrone. All of the antisense-expressing dones exhibited a decrease in thymidylate synthase and an increase in thymidine phosphorylase mRNA expression as determined by reverse transcription-PCR analysis and decreased levels of MDR-1 and MRP mRNA as determined by Northern blotting. These findings demonstrate that the inhibition of cyclin D1, in addition to suppressing the growth of pancreatic cancer cells, enhances their responsiveness to multiple chemotherapeutic agents and suggest that this effect may be due to the altered expression of several chemoresistance genes.

Adenocarcinoma↗

p53 in relation to therapeutic outcome of locoregional chemotherapy in pancreatic cancer.

Since celiac artery infusion (CAI) led to an increase in survival in palliative chemotherapy in pancreatic cancer, we treated 26 patients with adjuvant CAI following resection for advanced pancreatic cancer. Catheters were placed angiographically into the celiac artery and remained there for five consecutive days. One cycle of chemotherapy consisted of mitoxantrone, 5-fluorouracil (5-FU), folinic acid, and cis-platinum. This treatment was repeated five times in monthly intervals. Median survival times in patients who received CAI are 21 months for all patients, whereas in patients who did not receive adjuvant treatment median survival is 10.5 months. In all patients p53 expression of the carcinomas was determined by immunohistochemistry. In 11/26 patients a p53 overexpression was observed. Although p53 overexpression turned out to be associated with poor prognosis in the patients who underwent adjuvant regional cancer treatment, p53 is not a sufficient prognostic parameter in pancreatic carcinoma, since p53 overexpression was more frequent in undifferentiated tumors and in palliative resected tumors.

Adult↗

Levels of serum neopterin are increased in pancreatic cancer patients and correlate with the prognosis.

UNLABELLED: Neopterin has been recognized as a valid marker for cellular immune activation. Raised neopterin levels indicate the stimulation of macrophages and indirectly T-cell activation. So far no data is available on serum neopterin in pancreatic cancer patients. PATIENTS: In this prospective clinical study serum neopterin values were evaluated in 83 patients with adenocarcinoma of the pancreas (PC), 47 patients with chronic pancreatitis (CP), 8 patients with cystadenocarcinoma (CA) of the pancreas and 24 healthy controls (HC). RESULTS: Serum neopterin was significantly elevated in PC (p < 0. 05) and CA (p < 0.04) as compared to HC. There was no difference found between CP and HC. Pancreatic cancer patients with neopterin levels above 2 pmol/ml had a significantly better survival (p < 0. 05) regardless of stage. In stage III and IV (UICC) this difference was highly significant (p < 0.001). Serum levels of neopterin in resectable patients were also significantly correlated with increased survival and in multivariate analysis proved to be an independent prognostic factor. Neopterin in PC was neither correlated with sex, resectability nor with CA 19/9 and CEA. CONCLUSIONS: Patients suffering from PC who did show activated cellular immune response reflected in elevated neopterin levels above 2 pmol/ml had a significantly better prognosis regardless of tumor stage. In advanced stages elevated neopterin concentrations were significantly associated with increased survival. Cellular immune response seems to influence survival in these advanced stages to a higher degree as expected. These findings underline the possibility for supportive immunotherapy in this patient group.

Adult↗

Increased oxidative stress in the RAW 264.7 macrophage cell line is partially mediated via the S-nitrosothiol-induced inhibition of glutathione reductase.

We investigated whether endogenously or exogenously produced nitric oxide (NO) can inhibit cellular glutathione reductase (GR) via the formation of S-nitrosothiols to decrease cellular glutathione (GSH) and increase oxidative stress in RAW 264.7 cells. The specificity of this inhibition was demonstrated by addition of a NO-synthase inhibitor, and met- or oxyhemoglobin. Using isolated GR we found that only certain NO donors inhibit this enzyme via S-nitrosothiol. Furthermore, we found that cellular GSH decrease is paralleled by an increase of superoxide anion production. Our results show that the GR enzyme is a potential target of S-nitrosothiols to decrease cellular GSH levels and to induce oxidative stress in macrophages.

Animals↗

Expression and differential regulation of connective tissue growth factor in pancreatic cancer cells.

CTGF is an immediate early growth responsive gene that has been shown to be a downstream mediator of TGFbeta actions in fibroblasts and vascular endothelial cells. In the present study hCTGF was isolated as immediate early target gene of EGF/TGFalpha in human pancreatic cancer cells by suppression hybridization. CTGF transcripts were found in 13/15 pancreatic cancer cell lines incubated with 10% serum. In 3/7 pancreatic cancer cell lines EGF/TGFalpha induced a significant rise of CTGF transcript levels peaking 1-2 h after the start of treatment. TGFbeta increased CTGF transcript levels in 2/7 pancreatic cancer cell lines after 4 h of treatment and this elevation was sustained after 24 h. Only treatment with TGFbeta was accompanied by a parallel induction of collagen type I transcription. 15/19 human pancreatic cancer tissues were shown to overexpress high levels of CTGF transcripts. CTGF transcript levels in pancreatic cancer tissues and nude mouse xenograft tumors showed a good correlation to the degree of fibrosis. In situ hybridization and the nude mouse experiments revealed that in pancreatic cancer tissues, fibroblasts are the predominant site of CTGF transcription, whereas the tumor cells appear to contribute to a lesser extent. We conclude that CTGF may be of paramount importance for the development of the characteristic desmoplastic reaction in pancreatic cancer tissues.

Animals↗

Tumor of the ampulla of Vater: experience with local or radical resection in 171 consecutively treated patients.

HYPOTHESIS: This study was designed to evaluate prospectively oncological factors determining survival after resection of tumors of the papilla, comparing local and radical oncological resection. We hypothesized that, in malignant lesions of the ampulla, the T and N stages are major determinants of the patient's long-term outcome. BACKGROUND DATA: The frequency of malignant lesions in adenomas of the papilla is about 26%. Villous adenoma of the ampulla is considered a premalignant lesion. Local excision has been recommended for benign adenoma and pancreatoduodenectomy for malignant lesions. PATIENTS AND METHODS: From January 1, 1982, through June 30, 1997, 171 patients with tumors of the ampulla of Vater were surgically treated. Demographics, intraoperative factors, tumor pathological findings, and postoperative short- and long-term follow-up data were documented prospectively. Of the patients, 45 had adenoma of the papilla and 126 had malignant lesions of the ampulla. RESULTS: Local resection was performed in 40 of the 45 patients with adenoma. In 98 of the 126 patients with malignant lesions, a radical Kausch-Whipple resection or pylorus-preserving pancreatoduodenectomy was used. Of the patients with benign adenoma, 40 had local resection and 5 had pylorus-preserving pancreatic head resection, with a hospital mortality of 0%. Thirty of 35 patients had villous adenoma, 9 (30%) of the 30 with severe dysplasia. Of the 126 patients with malignant lesions, 98 had partial pancreatoduodenectomy and 10 had ampullectomy, with an overall hospital mortality of 3.1% for patients who underwent resection. Seventy-eight of the 98 patients had an R0 resection. The 5-year survival probability for all patients who underwent resection was 84% for cancer stage I, 70% for stage II, and 27% for stage III. In 8 patients with villous adenoma and carcinoma in situ and in 10 patients with cancer in the adenoma, ampullectomy with local lymph node dissection was performed. In 4 of the patients who had villous adenoma and a carcinoma in stage pT1 N0, an R0 resection was performed, resulting in cure of cancer. On the basis of a multivariate regression analysis, the prognosis after oncological resection of cancer of the ampulla is determined by the absence of lymph node metastasis (P<.05), the absence of infiltration into the pancreatic head tissue (P<.05), and the application of an R0 resection. CONCLUSIONS: In patients with villous adenoma of the ampulla, ampullectomy was an adequate surgical treatment. In patients with a low-risk cancer in stages pTis and pT1 N0 M0, G1 or G2, a local resection with ampullectomy including local lymph node dissection is justified. An oncological resection of cancer of the ampulla by means of a pylorus-preserving partial pancreatoduodenectomy or the Kausch-Whipple resection is the surgical procedure of choice; the 3- and 5-year survival rates were 72% and 52%, respectively, in patients with R0 resections.

Adenoma↗

[Surgical management of liver rupture].

The management of 178 patients with liver trauma (132 male, 46 female; mean age 34 years (range 3-88) presenting from January 1979 to August 1996 is reviewed. There were 165 cases of blunt trauma and 13 cases of penetrating injury. 110 cases were classified as simple injuries (grade I or II) and 68 cases as complex injuries (grade III to V). The overall mortality was 32% (57 patients). The mortality for true hepatic injury was 15.7%. None of the patients with penetrating injuries died. Mortality was influenced by the type of liver injury and the number of associated injuries. The postoperative complication rate was 55%. The most-frequent postoperative complications related to the hepatic injury were intrahepatic or subcapsular hematoma (12.9%) and postoperative bleeding (9.6%). Intraabdominal abscess formation was seen in 2.8%. Operative therapy for liver injuries depends on the grade of the injury. The majority of liver injuries can be managed by simple techniques, including electrocautery and application of hemostatic agents. In complex injuries hepatotomy, direct vessel ligation, and debridement of necrotic tissue is the method of choice (Pachter's procedure). In non-controlled bleeding, perihepatic picking is a standard method.

Adolescent↗

["No-puncture-laparoscopy" in hernia management in childhood--reliable complement to established therapy concepts].

BACKGROUND: Approximately 50% 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. The purpose of this study was to evaluate the usefulness of intraoperative laparoscopy in a non-puncture technique through the opened hernia sack. METHOD: In 112 children (age 6 months to 7 years) with clinical unilateral hernia laparoscopy (5 mm laparoscope, 30 degrees and 70 degrees). In cases of a wide-open contralateral internal inguinal ring (type III) open surgical exploration was performed. RESULTS: Nineteen patients (17%) fulfilled the laparoscopic criteria of a type III ring; the diagnose was confirmed during open contralateral exploration. Fourteen of these patients were younger than two years. The median time for laparoscopy was 6 min (3-11 min). No complications associated with the laparoscopy were observed. CONCLUSIONS: 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 an unnecessary routine bilateral open exploration. As an additional source of information through excellent visualization of the abdominal cavity, this method proved helpful to examine incarcerated bowel after repositioning.

Child↗

[Photodynamic ablation and argon-plasma coagulation of premalignant and early-stage malignant lesions of the oesophagus--an alternative to surgery?].

Eleven patients with high-grade mucosal dysplasia in a columnar-lined oesophagus and 2 patients with a squamous carcinoma (uT1) underwent photodynamic therapy (PDT) and argon-plasma coagulation (APC). For PDT, 5-aminolevulinic acid (5-ALA) was given orally (60 mg/kg) and treated endoscopically with a light dose of 150 J/cm2 (100 mW/cm2) at 635 nm 4-6 h later. A second PDT was performed under the same conditions 2-3 weeks later. Patients who received APC were treated 4 times on average to reach radical Barrett mucosa eradication. All patients were consistently given medication to suppress acid production. No complications occurred in either group. Follow-up endoscopies and multiple biopsies for 3-42 months showed squamous regeneration in the dysplastic columnar-lined oesophagus in all 11 patients. Two patients with squamous carcinoma were found to have a recurrence 9 and 12 months later. PDT with 5-ALA-induced endogenous prophyrins, as well as APC combined with omeprazole protection, can eradicate superficial high-grade dysplastic mucosa in Barrett's oesophagus. However, we did not succeed in destroying a manifest carcinoma.

Aged↗