[Is histological verification of pancreatic carcinoma a prerequisite for pancreas resection?].
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Biomarkers, Tumor↗
Biomedical subjects
H G Beger
Publications and source records attributed to H G Beger.
[Prognostic factors in pancreatic carcinoma].
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Carcinoma↗
Changes of protein gene product 9.5 (PGP 9.5) immunoreactive nerves in inflamed appendix.
The existence of chronic appendicitis is controversial. In this prospective study, we investigated possible changes in the innervation of the appendix under different pathological conditions and correlated histological findings with clinical observation. Thirty appendectomy specimens and 14 appendices obtained from organ donors or patients who underwent right hemicolectomy were immediately fixed in Bouin's solution and processed for immunocytochemistry using an antiserum directed against the panneuronal marker protein gene product 9.5 (PGP 9.5). The density of PGP 9.5 immunostaining was evaluated by digitized morphometry. Significant differences in the density of the PGP 9.5-immunoreactive area were detected in the mucosal layer. In the nonacute appendicitis group, PGP 9.5 was increased (10.99 +/- 3.15%) as compared to acute appendicitis (3.89 +/- 1.77%) and controls (4.98 +/- 1.25%). The significant increase of PGP 9.5 in nonacute appendicitis may suggest axonal sprouting leading to hyperinnervation of the mucosa. This may be a neuronal factor in the pathophysiology of the disease and pain symptoms.
Abdominal Pain↗
Altered expression of extracellular matrix molecules and their receptors in chronic pancreatitis and pancreatic adenocarcinoma in comparison with normal pancreas.
The aim of this study was to elucidate the expression and distribution patterns of both integrins and extracellular matrix (ECM) molecules in chronic pancreatitis (CP) and pancreatic adenocarcinoma (PC) compared with normal pancreas (NP). Expression of nine alpha-subunits (alpha 2-alpha 6, alpha V, alpha L, alpha M, and alpha X), four beta-subunits (beta 1, beta 3-beta 5), and four ECM molecules (type IV collagen, laminin, fibronectin, and vitronectin) was investigated immunohistochemically. In CP, all integrins except alpha V showed nearly the same staining patterns compared with NP. Some acinar cells in CP expressed alpha V. Whereas alpha 2, alpha 3, and alpha 6 expression was stronger and diffuse, no alpha 5 expression was seen in PC. Basement membrane (BM) showed continuous staining in CP, whereas it showed discontinuous/absent staining in PC with antitype IV collagen, laminin, and vitronectin antibodies. Some carcinoma cells showed reverse correlation between alpha 2, alpha 3, and alpha 6 expression and type IV collagen and laminin expression. Fibronectin showed diffuse stromal expression in CP and PC. Some acinar cells or duct cells in CP carcinoma cells in PC showed intracellular VN expression. These results suggest that these integrins and ECM molecules are involved in inflammatory and malignant processes in pancreas.
Adenocarcinoma↗
Randomized trial of duodenum-preserving pancreatic head resection versus pylorus-preserving Whipple in chronic pancreatitis.
BACKGROUND: In about 30% of patients, chronic pancreatitis leads to an inflammatory enlargement of the pancreatic head with subsequent obstruction of the pancreatic duct, common bile duct, and duodenum. METHODS: In a prospective, randomized controlled trial, we compared duodenum-preserving pancreatic head resection (DPPHR) with pylorus-preserving Whipple (PPW) operation to define the advantages of each operation with regard to (1) postoperative complications, (2) glucose tolerance and induction of diabetes mellitus, and (3) postoperative pain and quality of life up to 6 months after operation for chronic pancreatitis. RESULTS: The two study groups of 20 patients were both well balanced with regard to sex, age, history of chronic pancreatitis, and indication for surgery. Postoperative mortality was zero. After duodenum-preserving and pylorus-preserving resection, morbidity was 15% and 20%, respectively. After 6 months, patients who underwent the duodenum-preserving resection had less pain, greater weight gain, a better glucose tolerance, and a higher insulin secretion capacity. CONCLUSION: The DPPHR compares favorably with the standard PPW operation and should be considered as an alternative procedure in the treatment of chronic pancreatitis.
Adult↗
Endotoxemia and mediator release during colonoscopy.
BACKGROUND AND STUDY AIMS: Previous clinical and experimental studies have shown evidence of a leakage of whole bacteria and bacterial products after major trauma through the gut barrier. By determining plasma endotoxin levels, products of the arachidonic pathway, interleukin-6, and the endotoxin-neutralizing capacity (ENC) of plasma during colonoscopy, we studied the gut barrier function and the pathogenetic sequelae of mediator release during a minimally invasive procedure. PATIENTS AND METHODS: Thirty-two patients were enrolled in a controlled prospective study. Endotoxin and ENC were determined by a chromogenic modification of the limulus amebocyte lysate test. Prostanoids and interleukin-6 were measured using commercially available ELISA tests. C-reactive protein levels were checked by nephelometry. RESULTS: Twenty-one of the 32 patients had elevated endotoxin plasma levels during colonoscopy. In one patient, gut-derived bacteria were detected in plasma. ENC decreased after 5 min, and thromboxane B2 levels also started to increase at that time. No acute-phase response took place after 24 h. CONCLUSION: During colonoscopy, endotoxin can be detected in blood. ENC measurement was shown to be even more sensitive. The pathogenetic sequelae leading to gut barrier failure remain unclear, because mediator release and endotoxemia, as checked by ENC, took place simultaneously.
Adult↗
Oxidative stress in acute and chronic pancreatitis.
Oxygen radicals mediate an important step in the initiation of acute pancreatitis. These reactive oxygen metabolites are generated at an early stage of the disease. The source of the enhanced production of oxygen radicals, however, still remains unclear. Experimentally, the effectiveness of antioxidant treatment varies from one model to the other, the differences depending on the experimental model and not on the form of pancreatitis that was induced. In most studies, the experimental animals were pretreated before acute pancreatitis was induced. This does not mirror clinical reality because patients are admitted to the hospital after the onset of the disease. It was shown in cerulein-induced pancreatitis, however, that scavenger treatment also mitigated the pancreatic tissue damage after induction of acute pancreatitis. Moreover, antioxidant treatment also attenuated the extrapancreatic complications, thus improving the final outcome of the disease. Initial indirect observations also suggest that in human acute, acute recurrent, and chronic pancreatitis, oxygen free radicals are generated and add to the damage. Concomitantly, these patients suffer from a severe depletion of oxidative stress. Whether or not this disbalance is instrumental in the development and course of disease remains unanswered. Supplementation with antioxidants that are deficient in patients with acute pancreatitis might be a feasible option to the present therapy to avoid extrapancreatic complications. Well-defined, controlled clinical trials involving patients suffering from acute pancreatitis are therefore needed to validate the role of oxygen radicals in this disease.
Acute Disease↗
Endotoxemia and specific antibody behavior against different endotoxins following multiple injuries.
The aim of this study was to establish the incidence of endotoxemia and the influence of endotoxin on specific antibody response after multiple injury. Blood samples were collected from 39 patients (median Injury Severity Score: 20.5) at 0-3 and 6-12 hours, and 1, 3, 5, and 10 days after admission. The endotoxin plasma levels were high at the first time point (mean = 0.421 endotoxin units/mL) and decreased in the later course. Total immunoglobulin levels of IgM, IgG, or IgA were low and increased throughout the observation period. Specific antibodies of the IgM class against two lipid A and four lipopolysaccharide preparations increased transiently but significantly on day 3 and/or day 5. No changes of specific antibody content against endotoxin or lipid A was seen in the IgG or IgA class. The specific antibody content of the different classes against alpha-hemolysin of Staphylococcus aureus did not differ during 10 days after trauma. The specific antibodies of the IgM class reacted with all lipid A and LPS lipopolysaccharide preparations demonstrating cross-reactivity. These results suggest that endotoxin may be a specific stimulator of IgM antiendotoxin antibody secretion following trauma.
Adolescent↗
Lipid peroxidation and glutathione metabolism in chronic pancreatitis.
In experimental models of pancreatitis lipid peroxidation products are increased possibly because of an enhanced generation of oxygen radicals. The purpose of this study was to determine whether lipid peroxidation products are increased in pancreatic tissue and serum of patients suffering from chronic or acute pancreatitis. In 20 patients undergoing operative treatment for chronic (n = 11) and acute pancreatitis (n = 9) the levels of malondialdehyde, conjugated dienes, and reduced and oxidized glutathione were determined in resected tissue samples. The excised tissue was examined and evaluated by light microscopy. Shortly before operation the serum concentrations of malondialdehyde, alpha-amylase, and lipase were measured. Pancreatic tissue from eight organ donors who had no abdominal trauma or pancreatic disease served as control. In chronic pancreatitis, conjugated dienes as well as malondialdehyde concentrations in the tissue were significantly elevated. Reduced glutathione was significantly decreased, suggesting glutathione depletion due to oxidative stress. In acute pancreatitis only the tissue and serum malondialdehyde levels were significantly high, whereas conjugated dienes remained within the normal range. Serum malondialdehyde levels correlated significantly with tissue concentrations (r = 0.76; p < 0.05) but not with the clinical course or the enzyme levels. In chronic pancreatitis, the increased tissue levels of lipid peroxidation products and the changes in glutathione metabolism suggest ongoing peroxidation of lipids due to an enhanced generation of oxygen radicals. In hemorrhagic necrotizing pancreatitis, however, oxygen radical-induced lipid peroxidation cannot be proven. Apparently, other pathomechanisms are involved in the development of the severe tissue damage.
Acute Disease↗
Incidence and pathophysiological relevance of postoperative endotoxemia.
Patients who underwent surgical procedures usually develop elevated body temperature, changes of plasma levels of some proteins, and leucocytosis. These alterations are summarized as the postoperative acute-phase reaction. Also endotoxin can induce the described phenomena suggesting that endotoxin may play a role concerning the induction of the acute phase reaction. In order to test that hypothesis we determined endotoxin plasma levels preoperatively and daily postoperatively in patients who were operated on because of goiter (n = 20), colonic, pancreatic and gastric diseases (n = 58). A significant increase of endotoxin plasma levels was found at the first and third day after abdominal surgery whereas after goiter surgery the increase revealed to be only very slight. However, the decrease between the first and second postoperative day in the latter group was again statistically significant suggesting postoperative endotoxemia even after minor operations. Furthermore a correlation between the amount of circulating endotoxin and pulmonary or infectious complications could be established in patients after major operations even at the first postoperative day suggesting a pathogenetic relevance of postoperative endotoxemia.
Acute-Phase Reaction↗
Diagnosis of pancreatic cancer by 2[18F]-fluoro-2-deoxy-D-glucose positron emission tomography.
The detection of pancreatic cancer or the discrimination between pancreatic cancer and chronic pancreatitis remains an important diagnostic problem. The increased glucose metabolism in malignant tumours formed the basis for this investigation, which focused on the role of positron emission tomography (PET) with 2[18F]-fluoro-2-deoxy-D-glucose (FDG) in the detection of pancreatic cancer and its differentiation from chronic pancreatitis. Eighty patients admitted for elective pancreatic surgery received preoperatively 250-350 mBq FDG intravenously and emission scans were recorded 45 minutes later. Intense focal activity in the pancreatic region was taken at the time of scanning as showing the presence of pancreatic cancer. The presence of cancer was later confirmed by histological examination of the surgical specimens and histological findings were compared with the preoperative PET results. Forty one patients with pancreatic cancer (group I: n = 42) had a focally increased FDG uptake in the pancreatic region. Two patients with a periampullary carcinoma (group II: n = 6) failed to develop FDG accumulation. In 28 patients with chronic pancreatitis (group III: n = 32) no FDG accumulation occurred. Overall sensitivity and specificity of PET for malignancy (group I + II) were 94% (45 of 48) and 88% (28 of 32), respectively. The standard uptake value of the patients with pancreatic carcinoma was significantly higher than in patients with chronic pancreatitis (3.09 (2.18) v 0.87 (0.56); p < 0.001; median (interquartile range)). These findings show that FDG-PET represents a new and non-invasive diagnostic procedure for the diagnosis of pancreatic cancer and to differentiate pancreatic cancer from chronic pancreatitis. However, the diagnostic potential of this technique requires further evaluation.
Adult↗
Effect of acadesine treatment on postischemic damage to small intestine.
Hemorrhagic mucosal lesions are produced during intestinal ischemia and after reperfusion due at least in part to the accumulation and activation of polymorphonuclear leukocytes in the tissue. It has been shown in vitro that adenosine is instrumental in attenuating this pathophysiological process. Acadesine [5-amino-4-imidazolecarboxamide (AICA) riboside], a purine nucleoside analogue, increases the availability of adenosine in the tissue. The aim of the study was therefore to assess the influence of acadesine treatment on neutrophil accumulation, purine metabolism, and mucosal damage after intestinal ischemia and reperfusion. Intestinal ischemia was induced in cats by partial occlusion of the superior mesenteric artery for 2 h. Samples of the small intestine were exercised before and at the end of the hypotensive period as well as 10 and 60 min after reperfusion. Conjugated dienes, myeloperoxidase, and reduced and oxidized glutathione, as well as the purine metabolites, were determined in the tissue samples. The tissue was also examined histologically. Six cats received saline, and six cats were treated initially before ischemia with acadesine (2.5 mg/kg body wt i.v.) over 5 min as a bolus. Thereafter, acadesine (0.5 mg.kg-1.min- i.v.) was given continuously during ischemia and 30 min after reperfusion. Acadesine treatment significantly attenuated the mucosal lesions seen during reperfusion. This improvement was due at least in part to the inhibition of neutrophil accumulation, as judged by low myeloperoxidase levels. The prevention of neutrophil activation resulted most likely from increased adenosine concentrations in the intestinal tissue in the early reperfusion period.(ABSTRACT TRUNCATED AT 250 WORDS)
Aminoimidazole Carboxamide↗
Management of sterile necrosis in instances of severe acute pancreatitis.
BACKGROUND: The clinical management of sterile pancreatic necrosis is still a matter of debate. In this study we analyzed the clinical course and outcome of patients with sterile necrotizing pancreatitis treated surgically versus nonsurgically. STUDY DESIGN: Between May 1982 and December 1993, 249 patients with necrotizing pancreatitis (NP) entered this study, of which 172 (69 percent) had intraoperatively or fine needle aspiration-proven sterile NP. One hundred seven of 172 patients underwent surgery (S group) with necrosectomy and continuous postoperative closed lavage and 65 of 172 were treated by nonsurgical means (NS group). RESULTS: Median Ranson and admission APACHE II scores were 4.7 (range, 1 to 10) and 11 (range, 1 to 29) in the S group, significantly higher than those in the NS group with 3.0 (range, 0 to 6) (p = 0.022) and 8 (range, 1 to 23) (p = 0.036). After 48 hours of intensive care treatment, APACHE II scores persisted at 10.5 (range, 1 to 29) in the S group and decreased to 6 (range, 0 to 15) (p = 0.013) in the NS patients. Median C-reactive protein (CRP) levels on admission were 179 mg/L and 68.5 mg/L (p = 0.023), respectively. Within 72 hours, 61 (94 percent) of 65 NS-managed patients responded to intensive care therapy, whereas organ complications persisted or increased and thus led to surgery in the S group. Mortality rates were 13.1 percent in the surgically treated patients and 6.2 percent in the nonsurgically treated patients (p = NS). CONCLUSIONS: Most patients with limited and sterile pancreatic necrosis respond to intensive care treatment. Indication for surgery in sterile NP should be based on persisting or advancing organ complications despite intensive care therapy. APACHE II scores and admission CRP levels represent a helpful tool in decision making for surgical or nonsurgical management of NP.
APACHE↗
[Change in the surgical strategy in acute and complicated colonic diverticulitis].
The records of 312 patients with acute colonic diverticulitis were reviewed. 129 patients required an operation. The operative management is presented and compared to the international literature. One-stage resection was performed in 79% of all patients. In 84% of patients with a localized inflammation a one-stage resection was possible. Fifty-seven percent of patients with peritonitis due to colonic perforation required a multiple stage procedure. In 70% the preferred surgical procedure of multiple stage treatment was Hartmann's operation. These therapeutical regimens are current standard. Lethality was 1.6% for all 129 patients and the postoperative morbidity was 22%.
Acute Disease↗
[Endoscopic and surgical therapy of hemorrhagic duodenal and stomach ulcer].
The aim of this prospective clinical study was to evaluate whether a combination of the endoscopic hemostasis together with fibrin sealing and consecutive conservative therapy could reduce the frequency of recurrent bleedings, thus the number of operations without adversely influencing the prognosis of the disease. 134 patients admitted to the surgical and medical hospital of the University of Ulm between 1/1990 and 1/1992 with bleeding gastroduodenal ulcers took part in this study. All patients were treated endoscopically by hypertonic saline solution plus epinephrine and fibrin sealant. If initial endoscopic hemostasis was not achieved patients were operated within 6 h after admission. Patients with successful initial endoscopic hemostasis were treated conservatively and underwent control endoscopy after 24 and 48 h. In 23 patients the initial endoscopic hemostasis was not successful, they had to be operated immediately. In 111 patients endoscopic hemostasis was achieved, 20% of these patients had acute bleeding ulcers (Forrest Ia, b), 66% showed stigmata of fresh bleedings (Forrest-IIa bleeding). Primary endoscopic hemostasis was achieved in 85.6% of all patients treated, 14.4% of patients (n = 16) developed a recurrent bleeding during the observation period verified by gastroscopy. Half of these patients had an acute bleeding at the first gastroscopy (Forrest-Ia, Forrest-Ib bleeding). Recurrent bleeding became apparent between day 1 and 6 after admission to the hospital. Two patients refused surgical intervention, the other 14 were operated immediately.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
[Diagnosis and therapy of primary pancreatic abscess].
Local septic complications in acute pancreatitis (AP) should be characterized and defined in order to assess the validity of early diagnosis and various therapeutic measures. The purpose of this study was therefore to distinguish between two local septic complications which have been termed 'abscess' and 'infected necrosis' in regard to their morphological, clinical, laboratory criteria. Moreover, the validity of various diagnostic procedures and therapeutic interventions were compared. Septic necrosis is defined as a diffuse bacterial inflammation of necrotic pancreatic and peripancreatic tissue. The morphologic substrate of pancreatic abscess is a localized collection of pus surrounded by a capsula or pseudocapsula. Infected necrosis become clinically evident in the early phase of AP. The patients suffer from a fulminant course of AP with signs of sepsis and laboratory alterations typical for AP. Concomitantly, these patients develop pulmonary and renal insufficiency, in 71.5 and 44.2% of the patients, resp. Overall mortality rate of patients with infected necrosis amounts to 20.8%. In contrast, pancreatic abscess develops not before week 5 after onset of AP. Concomitantly, the laboratory signs of AP like amylasemia and hypocalcemia as well as LDH and C-reactive protein increases are rarely observed. Correspondingly, these patients suffer significantly less form pulmonary insufficiency (22.6%) or other organ complications. Consequently, the mortality rate is with 6.5% significantly lower. Timely diagnosis is possible with acceptable sensitivity by contrast-enhanced CT scan and fine-needle aspiration. Other imaging procedures do not show similar sensitivity and specificity. Therapeutically, patients with infected necrosis as well as pancreatic abscess have to be operated.(ABSTRACT TRUNCATED AT 250 WORDS)
Abscess↗
[Oxygen radicals and postischemic organ damage--pathophysiology, clinical relevance and therapy].
Postischemic damages after ischemia and reperfusion are of growing clinical relevance. It was assumed that these damages were due to hypoxia. It has been shown that during reperfusion oxygen radicals are generated in high concentrations adding significantly to the damage. These oxygen radicals are generated by the hypoxanthine-xanthine oxidase system. They do not only damage directly but trigger the accumulation and migration of PMN-leukocytes within the inflicted tissue. PMN-leukocytes induce a non-specific postischemic inflammatory reaction which is responsible for the severe reperfusion damages. Oxygen radicals can be treated successfully by so-called radical scavengers. Thereby, it is essential to initiate the therapy during the so-called "therapeutic window", a time interval in which reperfusion aggravates the ischemic lesions. Only few clinical studies have been performed. The results concerning scavenger treatment after myocardial infarction have been disappointing. In transplantation surgery, however, antioxidative therapy has proven to be beneficial. Well-defined double blind randomized well-stratified clinical studies are now essential in order to assess the possibilities of antioxidative therapy after time-limited ischemia and reperfusion.
Antioxidants↗
A multicenter study of phospholipase A2 in patients in intensive care units.
BACKGROUND: Multiple organ failure (MOF) is becoming the most common cause of death in patients in surgical intensive care units. In this respect, a multicenter study in four different groups of patients in surgical intensive care units was done to evaluate the role of phospholipase A2 (PLA2) in comparison with C-reactive protein (CRP) and polymorphonuclear (PMN) elastase. STUDY DESIGN: A total of 223 patients entered the study: 73 patients with multiple injuries, 46 patients with diffuse peritonitis, 52 patients with sepsis, and 52 patients in a control group who were at a higher risk for postoperative sepsis after defined surgical interventions. The patients underwent a daily monitoring of PLA2, CRP, and PMN elastase for seven days. RESULTS: Phospholipase A2 activity remained within the normal range in patients with multiple injuries and patients in the control group, indicating that this parameter is not influenced by the postaggression metabolism. In contrast, in patients with peritonitis, high PLA2 values were found from the beginning. The efficiency for predicting a lethal MOF was 85 percent for PLA2 (cut-off 80 U/L) in patients if determined at the day of operation. A comparably favorable efficiency (84 percent) was demonstrated for PMN elastase in patients with multiple injuries (cut-off 205 micrograms/L) measured at day one. CONCLUSIONS: These efficiency rates of PLA2 in peritonitis and PMN elastase in multiple injuries were comparable or even better than multifactorial scoring systems used in the study. C-reactive protein did not contribute to an early estimation of the prognosis in all groups analyzed. Therefore, the measurement of PLA2 in patients with diffuse peritonitis and PMN elastase in patients with multiple injuries, as single parameters, is recommended to estimate the individual risk for the occurrence of lethal MOF.
Adolescent↗