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H Lippert

Publications and source records attributed to H Lippert.

At least 55 records · Page 3Linked to original sources
PubMed2001

A proteinase inhibitor decreases tumor growth in a laparoscopic rat model.

BACKGROUND: The balance between proteolysis and protease inhibition in the formation and breakdown processes of the extracellular matrix plays a major role in tumor cell invasion. An understanding of this relationship gave rise to the therapeutic concept of lowering tumor cell invasion by inhibiting protease activity. Phosphoramidon is an unspecific proteinase inhibitor. This experimental study investigated the effect of intraperitoneal phosphoramidon administration on tumor growth in a laparoscopic rat model. METHODS: In the first phase of the study, we investigated the influence of phosphoramidon on tumor cell invasion in a collagen matrix gel chamber in vitro. In a second experiment, a suspension of colon carcinoma cells (CC531) was introduced into the peritoneal cavity of male WAG rats. Prior to laparoscopy (at 6 mmHg for 20 min), the animals were randomized to two groups. At the start of laparoscopy, the test substance was applied intraperitoneally (group 1: controls, 1 ml 0.9% NaCl; group 2: 250 mg phosphoramidon in 1 ml 0.9% NaCl). Three weeks after the injection of tumor cells, the animals were autopsied and the tumor mass determined. RESULTS: In comparison with the control group (tumor weight 7.42 +/- 1.01 g), intraperitoneal tumor growth in the experimental group was significantly (p < 0.001) reduced by the application of phosphoramidon (tumor weight, 3.22 +/- 1.06 g). Phosphoramidon also significantly (p < 0.05) reduced tumor cell invasion through the matrix gel. CONCLUSION: The proteinase inhibitor phosphoramidon reduced tumor cell invasion in vitro and tumor cell growth in vivo in this laparoscopic rat model.

Animals↗
PubMed2001

[Hepatobiliary cystadenoma].

INTRODUCTION: Hepato-biliary cystadenomas are rare intrahepatic cystic tumours. The correct preoperative diagnosis of this lesion is difficult. METHODS: We report four cases of hepato-biliary cystadenoma treated in our department from January 1995 to December 1999. RESULTS: The symptoms were unspecific. Preoperative computed tomography showed signs of an echinococcal cystic lesion in two patients, but there were no antibodies against an echinoccocal species in the serum. We performed a complete resection of the cystic tumour in three patients and a subtotal resection of a hepato-biliary cystadenoma in one, because of involvement of the hepatic portal structures. We did not find a malignant transformation to a hepato-biliary cystadenocarcinoma. CONCLUSION: Complete excision of a cystadenoma with a wide margin of normal liver tissue is the treatment of choice, because several reports have described malignant transformation of this kind of tumour. Taking a rapidly frozen section during the operation is an important step in the treatment of cystic liver lesions. A cystic liver lesion with several walls and a elevated CA 19-9 can predict a mucinous cystadenoma or cystadenocarcinoma.

Adult↗
PubMed2001

[Strategy and technique in perineal impalement injuries].

Injuries of the anal sphincter and the pelvic floor are rare and have a large range of variations. This report is based upon 28 patients with perineal injuries treated in a 17-year period. Mortality depends on accompanying injuries. The degree of the injury determines the functional result. Proximal diversion and drainage represent the standard treatment for intra-abdominal rectal injuries. In extraperitoneal rectal injuries diversion, presacral drainage and distal rectal washout is recommended. Loss of continence is the most severe complication of injuries of the anal sphincter. The best results are obtained by primary repair.

Abdominal Injuries↗
PubMed2001

[Value of cytokeratin and Ca 19-9 antigen in immunohistological detection of disseminated tumor cells in lymph nodes in pancreas carcinoma].

INTRODUCTION: Based on the fact that pancreatic carcinoma is still associated with poor outcome, the aim of the study was to determine frequency of early tumor cell dissemination using immunohistology in lymph nodes classified as tumor-free by conventional histopathology. METHODS: Fifteen patients with ductal pancreatic carcinoma and 10 patients with carcinoma of the papilla of Vater underwent radical tumor resection (resection status R0, tumor staging pTxpN0M0). In total, 229 lymph nodes classified as tumor-free by histopathology were investigated for disseminated tumor cells using antibodies against cytokeratin and CA19-9. As control, 81 lymph nodes obtained from patients with chronic pancreatitis were analyzed. RESULTS: In 55 of 229 lymph nodes (26.3%), cytokeratin-positive, disseminated tumor cells were detected. Cytokeratin-positive cells were found in at least one resected lymph node of each patient with ductal carcinoma of the pancreatic head (100%), whereas in patients with carcinoma of the papilla of Vater, no disseminated tumor cells were detected using the antibody against cytokeratin. Similarly, there was no detection of tumor cells (false-positive) in patients with chronic pancreatitis. In contrast, CA19-9 antigen was detectable in resected lymph nodes of each of the 25 carcinoma patients (pancreatic carcinoma and carcinoma of the papilla of Vater). Interestingly, 52 of 81 lymph nodes (64.2%) from the control group (chronic pancreatitis) were false-positive. CONCLUSION: Detection of disseminated tumor cells in lymph nodes using an antibody against cytokeratin is specific and suitable while use of an antibody against CA19-9 is not recommendable because of the high rate of false-positive results. The results may indicate that ductal pancreatic carcinoma generates early dissemination of tumor cells into lymph nodes. This may be one explanation for the poor outcome of this carcinoma compared with that of the carcinoma of the papilla of Vater (14 versus 48 months P < 0.05).

Adenocarcinoma↗
PubMed2001

Effect of caseload on the short-term outcome of colon surgery: results of a multicenter study.

This prospective multicenter study investigated the effect of hospital caseload on early postoperative outcome of surgery for carcinoma of the colon in 75 German hospitals and included 2293 patients. The hospitals were divided into those with a caseload of 1-30 (group A), 31-60 (group B), and more than 60 (group C) operations. Increasing caseload was associated only with fewer general postoperative complications. It was also associated with significantly greater use of antibiotic prophylaxis. No significant differences between the groups were found in resection rates, intraoperative complications, specific postoperative complications, overall postoperative morbidity, hospital mortality, or 30-day mortality. The significance of hospital caseload for the short-term postoperative outcome following surgery on the colon should not be overestimated. Basing conclusions about the results to be expected simply on the case volume is impermissible. On the basis of the available data it is not possible to establish a threshold value, that is, a minimum number of required operations.

Adenocarcinoma↗
PubMed2001

Prophylaxis of peritoneal carcinomatosis in experimental investigations.

BACKGROUND AND AIMS: We compared the effectiveness and side effects of various cytostatic agents for use in perioperative intraperitoneal irrigation to prevent peritoneal carcinomatosis. METHODS: The adenocarcinoma cell line CC-531 was implanted during laparotomy at the mesenterial trunk of anesthetized male WAG rats. Direct perioperative intraperitoneal chemotherapy was performed after 5 min with either 5-fluorouracil, cisplatin, or mitomycin; controls received only tumor cells. The animals were inspected daily over 30 days for side effects. They were then killed, and the greater omentum and mesentery were resected, the tumor mass was examined for the presence of peritoneal carcinomatosis, and tumor nodules in the greater omentum and mesentery were counted. RESULTS: All the animals in the control group developed histologically confirmed peritoneal carcinomatosis. Animals receiving cisplatin or mitomycin by direct intraperitoneal perioperative chemotherapy showed no macroscopic or histological evidence of tumor growth. Two animals in the fluorouracil group had macroscopically and histologically manifest tumor growth; another animal showed only histological evidence of malignancy. Substantial side effects were noted in the cisplatin group, with all animals experiencing bleeding in the peritoneum and toxic necrotic reactions of the colon; two animals died of these side effects. CONCLUSION: Direct intraperitoneal chemotherapy with cisplatin or mitomycin prevents peritoneal carcinomatosis in experimental investigations.

Adenocarcinoma↗
PubMed2001

Can a coated Dacron vascular graft maintain a heparin-induced thrombocytopenia type II?

In the course of reconstruction of peripheral arterial occlusion processes, two gelatin-coated Dacron grafts and one collagen-coated Dacron patch were implanted in a 52-year-old male patient. Eight days following low-dose heparinization (5 days prior to surgery, 3 days postoperatively) with unfractionated heparin, with no clinical symptoms present, a dramatic isolated thrombocyte depression occurred, from 212 Gpt/l prior to surgery to 14 Gpt/l on postoperative day 3. Laboratory tests verified an HIT type II [heparin-induced platelet aggregation assay (HIPAA) and ELISA]. Despite immediate discontinuation of heparin and commencement of an anticoagulant therapy with Revasc and Refludan, an 8-week thrombocyte depression occurred which was eliminated only temporarily by administration of gammaglobulin. The specific antibody tests turned out positive for more than 5 months. Having ruled out other causes of thrombocytopenia, we assume that the case presented was either due to an interaction not elucidated to date or triggered by the grafts (gelatin/collagen/Dacron). The manufacturers of the grafts have disputed a heparinoid action.

Arterial Occlusive Diseases↗
PubMed2001

Induction and expression of cyclin D3 in human pancreatic cancer.

PURPOSE: Cyclins play a key role in the control and regulation of the cell cycle. The role of cyclins in the pathogenesis of pancreatic cancer is largely unknown. METHODS: Using Northern blot analysis, polymerase chain reaction (PCR) and immunohistochemistry, we examined the expression of cyclins D1, D2, and D3 in human pancreatic cancer and studied the induction of these cyclins by growth factors in pancreatic cancer cell lines. RESULTS: We now report that cyclin D1 and D3 mRNAs are expressed in human pancreatic cancer cell lines, and that the expression of cyclin D3 is enhanced in pancreatic cancer cells by amphiregulin, a member of the epidermal growth factor family. Cyclins D1 and D3 are also expressed in normal and malignant pancreatic tissues. However, while the normal pancreas and pancreatic cancers express cyclin D2 as determined by reverse-transcriptase PCR, we could not detect cyclin D2 mRNA by either Northern blot analysis or reverse transcriptase PCR in the two pancreatic cancer cell lines. Immunohistochemical analysis revealed the expression of cyclin D3 in pancreatic cancer cells. CONCLUSIONS: These findings suggest that D-type cyclins are differentially expressed in pancreatic cancer and that the aberrant activation of the EGF receptor in human pancreatic cancer by amphiregulin may lead to the progression of the cell cycle via induction of cyclin D3 expression, thus contributing to the growth advantage of these transformed cells.

Amphiregulin↗
PubMed2001

Combination chemotherapy with docetaxel and cisplatin for locally advanced and metastatic gastric cancer.

BACKGROUND: Poor treatment results obtained with palliative chemotherapy for advanced gastric cancer indicate the need for new effective and well-tolerated regimens. PATIENTS AND METHODS: Forty-three patients with locally advanced or metastatic gastric cancer were enrolled in a phase II study to evaluate the efficacy and safety of combination chemotherapy with doxetacel 75 mg/m2 and cisplatin 75 mg/m2 given every three weeks. RESULTS: Thirty-nine patients were evaluable for response. Four achieved a complete response and twelve a partial response, for an overall response rate of 37.2% (16 of 43 patients; 95% confidence interval (CI): 22.98-53.72). Median time to progression was 6.1 months and median overall survival 10.4 months. Forty-two percent of all patients were still alive at one year and twelve percent at two years. The major toxicity was leukopenia which reached grade 3-4 in 18.6% (n = 8) of the patients. However, no febrile neutropenia occurred. Non-haematological toxicities were usually mild to moderate. Grade 3 toxicities included diarrhea (9% of the patients), nausea and vomiting (7%), and alopecia (7%). Severe ototoxicity with or without peripheral neuropathy developed after completion of chemotherapy in two patients. CONCLUSIONS: These results suggest that the combination of docetaxel and cisplatin has moderate toxicity and is an effective regimen for the treatment of advanced gastric cancer, both with regard to response rate and survival.

Adult↗
PubMed2001

Differential oxidative injury in extrapancreatic tissues during experimental pancreatitis: modification of lung proteins by 4-hydroxynonenal.

Oxidative stress is considered to be a pathogenic factor for multisystem organ failure during acute pancreatitis. Infusion of 3% and 5% sodium taurocholate into the pancreatic duct of rats resulted in a 24-hr lethality of 8% and 82%, respectively. Kidney tissue showed a long-lasting significant elevation of malondialdehyde (lipid peroxidation). Only small amounts of this aldehyde were formed in the liver. In the lung malondialdehyde was increased during the first 6 hr after pancreatitis induction. Malondialdehyde levels were not different for pancreatitis initiated by 3% or 5% taurocholate. Protein-bound carbonyls (protein oxidation) in the tissues were not significantly changed at any time point. However, after infusion of 5% taurocholate, lung proteins were oxidatively modified by the product of lipid peroxidation, 4-hydroxynonenal. Another parameter characteristic for pancreatitis with high lethality was the high number of neutrophils in the lungs. We conclude that oxidative stress is important for the injury of extrapancreatic tissues during pancreatitis, but survival is determined by the degree of systemic inflammation.

Aldehydes↗
PubMed2001

Hospital caseload and the results achieved in patients with rectal cancer.

BACKGROUND: The aim of the study was to investigate the impact of hospital caseload on the short-term postoperative outcome of patients with rectal carcinoma. METHODS: A multicentre study involving 75 German hospitals was carried out between January and December 1999. Some 1463 patients with rectal carcinoma were studied. RESULTS: The hospitals were divided into three groups by annual caseload as follows: less than 20 (group 1), 20-40 (group 2) and more than 40 (group 3). The groups were identical in terms of age, gender, height, weight, tumour stage, risk factors and American Society of Anesthesiologists classification. Postoperative morbidity was less in hospitals with a case volume of more than 20 patients per year (41.7 per cent in group 2 versus 49.9 per cent in group 1). The proportion of patients undergoing abdominoperineal resection with a permanent stoma was less in hospitals with a case volume of more than 40 patients per year (26.4 per cent in group 3 versus 34.0 per cent in group 2). CONCLUSION: A large caseload in rectal surgery results in a significant reduction in permanent stoma formation and postoperative morbidity.

Anastomosis, Surgical↗
PubMed2001

[Quality assurance study of benign and malignant goiter. Prospective multicenter data collection regarding 7,617 patients].

A quality control study was undertaken on 7,265 patients with benign goitre and 352 patients with malignant goitre who were surgically treated between 1.1.98 and 31.12.98. 3 hospital groups were defined according to surgical workload: Group 1: < 50 operations/yr; Group 2: 50-150 operations/yr; Group 3: > 150 operations/yr. The temporary rate of recurrent laryngeal nerve (RLN) palsies for benign goitre was 3.9% and the permanent 1.1%. For malignant goitre the rates were 12.8% and 6.8% respectively. The rate of temporary (p < 0.040) and permanent (0.003) palsies after surgery for benign goitre was lower in group 3 compared to group 1 and 2. There were too few cases for statistical analysis of the malignant goitres. After benign goitre surgery a transient hypocalcaemia rate of 6.3% and a permanent of 1.1% were observed. For malignant goitre the incidence was 23.8% and 7.1%, respectively. A significantly increased rate of permanent hypocalcaemia (p < 0.003) was demonstrated in group 3 after surgery for multinodular goitre. Centres in group 3 made more extended (smaller thyroid remnants) resections (p < 0.01) with the equivalent rate of general complications. The average inpatient stay for malignant goitres was 13.1 days and for benign goitres 8.7 days. On average, patients with bilateral resections for benign goitre stayed 0.4 days longer in hospital than those with unilateral procedures. Prophylactic antibiotics were administered to 2.1% of patients and 94.6% received thrombosis prophylaxis.

Adult↗
PubMed2001

[Enzymatic and histological alterations in the isolated perfused rat pancreas in the taurocholate and cerulein model of acute pancreatitis].

METHODS: The pancreas of 24 male Wistar rats was perfused extracoporally by modified Krebs-Ringer-buffer for 80 minutes (including a 20 minutes equilibration period). To verify any organ damage we measured the activity of pancreatic enzymes like amylase, lipase and lactatdehydrogenase in the portal effluent. Furthermore histological changes were analysed after perfusion. Organ damage was induced by adding cerulein in a physiological dose (10(-10) M, n = 6) and in a supramaximal dose (10(-8) M, n = 6) and by intraductal injection of taurocholate (3.5 %, n = 6). RESULTS: Already 10 minutes after stimulation with cerulein (10(-8) M) and after intraductal injection of taurocholate increased activities (p < 0.01) of amylase and lipase were measured in the portal effluent compared to the group without any treatment. Lactatdehydrogenase levels did not changed. Apart from marked oedema in both groups considerable zones of necrosis could be noticed especially in the taurocholate group. CONCLUSION: Our data suggest that the isolated perfused rat pancreas (IPRP) is a valuable experimental tool to verify pathophysiological changes in the early phase of acute pancreatitis (AP). Various established models of AP such as by cerulein hyperstimulation or intraductal injection of taurocholate, could be applied to the IPRP. We conclude that this method enlarges the spectrum of established experimental models of acute pancreatitis.

Acute Disease↗
PubMed2001

[The isolated perfused rat pancreas - an experimental model for investigation the early events in the pathogenesis of acute pancreatitis].

METHODS: External perfusions of the pancreatic glands of Wistar-rats were done, using a modified Krebs-Ringer-Buffer (KRB). We looked for an elevation of amylase, lipase and lactate-dehydrogenase in the effusion fluid (portal outflow fluid). We investigated a normal perfusion (KRB, 60 minutes), a long term perfusion (KRB, 240 minutes) and a perfusion (60 minutes) including an additive of the detergents triton x-100 or the cholecystokinin analogue ceruletid (10(-8) M). RESULTS: An isolated external perfusion of a rat pancreas is possible without inducing any increase of parameters of damage such as amylase, lipase or lactate-dehydrogenase in the outflow medium. The perfusion time should be limited to 80 minutes including a 20 minutes equilibration period. A damage of pancreatic parenchyma is indicated by increased levels of pancreatic enzymes in the perfusion medium. Such damage can be induced by various noxious substances like detergents or cerulein, which has a significance in the pathophysiology of experimental acute pancreatitis. A significant increase (p < 0.01) of lactate-dehydrogenase, lipase and amylase was found 10, 20 and 30 minutes after an application of triton x-100. During a perfusion with the cholecystokinin analogue ceruletid (10(-8) M) we found an increase of lipase (p < 0.05) after 30 minutes and an increase of amylase (p < 0.05) after 50 minutes perfusion. CONCLUSIONS: The isolated perfused rat pancreas is a valuable experimental model to investigate the early phase of pathophysiology in acute pancreatitis.

Acute Disease↗
PubMed2001

Real-time assessment of intraperitoneal tumor growth in a rat model using CEA immunoscintigraphy.

BACKGROUND: In most preclinical models, assessment of intraperitoneal tumor location and size require killing the animal. The dynamics of postoperative intraperitoneal tumor implantation and growth remain unclear. A noninvasive method allowing reliable in vivo, real-time assessment of tumor growth is desirable. METHODS: An intraperitoneal tumor homograft using cultured CC531 colorectal cells was created by laparotomy in 24 Wistar Albino Glaxo rats. Eight additional rats were used as controls. Then, 10 MBq technetium 99m-labeled anticarcinoembryonic antigen (anti-CEA) monoclonal antibodies were administrated intravenously and radioactivity uptake was measured by using extracorporeal gamma counting at various time points. Subsequently, the animals were killed for tumor weighting. In 2 more groups of 8 animals, real-time, repeated measures were performed. RESULTS: Correlation between gamma counting and tumor weight was highly significant (P <.001). The regression equation obtained by using the least squares method was: tumor weight (g) = 2.422 + 0.267 x counts. It was possible to obtain real-time tumor growth curves when repeated measurements of radioactivity were performed. At day 25, the predicted tumor weight was 8.49 +/- 0.76 g, the measured weight was 8.16 +/- 0.99 g. CONCLUSIONS: Immunoscintigraphic measurements with technetium 99m anti-CEA antibodies are highly correlated with tumor weight in this model. As opposed to other tumor graft models based on autopsy findings, real-time monitoring is possible. This will allow dynamic studies of intraperitoneal tumor implantation and growth and will reduce the number of animals used in further studies.

Animals↗
PubMed2001

Randomized, placebo-controlled trial of lazaroid effects on severe acute pancreatitis in rats.

OBJECTIVES: To evaluate the therapeutic potential of lazaroids in severe necrotizing acute pancreatitis and to investigate the association between oxidative stress, protease activation, and local production of proinflammatory cytokines and the severity and lethality of the disease. BACKGROUND: Oxidative stress is a crucial factor in the pathophysiology of acute pancreatitis and its systemic complications. Treatment with antioxidants, however, failed to improve survival in most studies performed so far. Lazaroids are a novel class of antioxidants that potently protect pancreatic acinar cells against oxidant attack in vitro. DESIGN: Prospective, randomized, controlled experimental study. SETTING: University research laboratory. SUBJECTS: Seventy-five anesthetized male Wistar rats (300-350 g). INTERVENTIONS: Severe acute pancreatitis was induced by retrograde injection of 3.5% taurocholate-sodium into the common bile-pancreatic duct. Interventions were performed to mimic the clinical situation, including continuous intravenous fluid substitution and administration of lazaroids in a therapeutic protocol. Therapy was started 1 hr after injection of the bile salt by using three different lazaroids, lactated Ringer's solution (placebo), and methylprednisolone as a corticosteroid control (n = 15 in each group). All the substances were given by continuous intravenous infusion throughout the 20-hr trial period. MEASUREMENTS AND MAIN RESULTS: Pancreatic homogenates and ascites were analyzed for indicators of oxidative stress, antioxidants, proteases, and proinflammatory cytokines. Pancreatic edema, morphologic pancreatitis severity, and pancreatic histopathology also were assessed. All three lazaroids and methylprednisolone diminished pancreatic tumor necrosis factor-alpha concentrations. Lethality was 33% in the placebo group. Neither the lazaroids nor methylprednisolone influenced survival. The local pancreatic and peritoneal concentrations of lipid peroxidation products, antioxidants, and proteases did not differ among the five groups. Nonsurviving rats, however, had a higher total protease activity in the pancreas and higher concentrations of trypsinogen activation peptide in ascites, as compared with surviving animals. There were no differences between survivors and nonsurvivors with regard to variables of oxidative stress and cytokines. CONCLUSIONS: Lazaroid application under clinically relevant conditions (i.e., after induction of fulminant acute pancreatitis) does not influence lethality or biochemical variables relevant to this disease. Protease activation rather than oxidative stress or local pancreatic cytokine production is an important determinant of disease severity and survival in acute pancreatitis. In experimental studies evaluating novel therapeutics, the same strict criteria should be applied as in the human setting.

Animals↗
PubMed2001

Prognostic parameters determining survival in pancreatic carcinoma and, in particular, after palliative treatment.

Prognosis and outcome of patients with pancreatic carcinoma is poor. The aim of the study was to investigate (1) which factors of medical history and clinical status as well as which laboratory parameters determine survival in pancreatic carcinoma and (2) whether specific data can be used as prognostic parameters or for early diagnosis of pancreatic carcinoma. In total, 287 patients with pancreatic carcinoma were enrolled in the study. In 193 subjects, only palliative treatment was possible. Survival was assessed using univariate survival probability curves by Kaplan-Meier. Comparison of patient groups with regard to survival was achieved using the log-rank test. Multivariate analysis was carried out using the Cox regression model. Overall, 22 factors, showing a significant impact on survival in pancreatic carcinoma were found, e.g., tumor-associated factors such as (1) tumor stage according to the UICC classification including TNM-based staging, grading, tumor site, and vascular infiltration; (2) preoperative habits and signs and symptoms (physical condition, pain, loss of appetite, ethanol consumption); (3) change of laboratory parameters (CA 19-9, bilirubin, prothrombin time, urea, C-reactive protein), and (4) type of intervention (surgical approach, R0/1/2 resection). Using multivariate analysis, seven factors (UICC tumor stage and site, surgical intervention including number of resected lymph nodes, chemotherapy, occurence of a carcinoma in relatives, preoperative physical condition, night sweat) were determined. In the 193 patients with palliative treatment, only ten factors (among them UICC tumor stage including the presence of metastases; data from the medical history such as physical condition, loss of appetite, and carcinoma in relatives, and laboratory parameters including prothrombin time, protein content, and aspartate aminotransferase levels) were found to be important. Chemotherapy had the strongest impact on survival which was confirmed by multivariate analysis, followed by tumor stage (UICC) and preoperative appetite. Besides tumor-associated determinants, data from the medical history, and pathological laboratory parameters, the prognosis in pancreatic carcinoma is considerably determined by the treatment such as interventional and/or using antineoplastic agents.

Adult↗