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T Foitzik

Publications and source records attributed to T Foitzik.

At least 19 recordsLinked to original sources
PubMed2006

Concurrent chemoradiation with capecitabine and weekly irinotecan as preoperative treatment for rectal cancer: results from a phase I/II study.

The aim of this study was to investigate the efficacy and safety of chemoradiation using capecitabine and irinotecan as neoadjuvant therapy for patients with rectal cancer. Conventional radiation was given at daily fractions of 1.8 Gy on 5 days a week for a total dose of 55.8 (50.4 + 5.4) Gy. Concurrently, irinotecan 40 mg m(-2) once weekly and capecitabine continuously at dose levels of 500, 650, 750 and 825 mg m(-2) twice daily were administered. Surgery was performed 4-6 weeks following completion of chemoradiation. A total of 28 patients (3 UICC II, 25 UICC III) were enrolled and all received treatment. Dose-limiting toxicity was diarrhoea grade IV and hand-foot syndrome at the 825 mg m(-2) dose level. The maximum tolerated dose of capecitabine was 750 mg m(-2). Diarrhoea was the most common toxicity: grade III in nine patients. Two patients died, one due to pneumonia and one due to sudden cardiac death. A complete response and only microfocal residual tumour disease was achieved in four and three patients (27%). In all, 25 of 28 patients undergoing surgery, 24 (96%) had R0 resection. Preoperative chemoradiation based on continuous daily capecitabine and weekly irinotecan appears to tolerated and effective in patients with rectal cancer.

Aged↗
PubMed2006

Octreotide hardens the pancreas.

BACKGROUND AND AIMS: Leakage from pancreaticojejunostomy and development of pancreatic fistulas are the major postoperative complications in patients undergoing duodenopancreatectomy. The risk of developing these complications is higher when surgery is performed on a soft pancreas. A recent report suggests that octreotide hardens the pancreas when given intraoperatively. The present study aims at verifying this observation by measuring tissue hardness of the pancreas by a commercially available durometer in pigs with and without octreotide pretreatment. METHODS: Three groups of pigs were investigated: Group 1 (n=6) received no treatment; group 2 (n=6) was treated with 3x100 microg octreotide for 1 day; group 3 (n=6) for 5 days. Thereafter, animals were killed and the pancreas was harvested for performing measurements: Tissue hardness was assessed by a commercially available durometer, and a suture holding test was performed using a Newton dynamometer. RESULTS: There was a significant increase in tissue hardness between untreated control animals [26.3+/-2.5 S.U. (shore units)] and animals with 1 day octreotide pretreatment (29.8+/-2.6 S.U.; p=0.04) as well as between the groups treated for 1 and 5 days (34.8+/-2.8 S.U.; p=0.01). Suture holding capacity was higher in animals treated for 5 days. CONCLUSION: The present study agrees with a recent report suggesting that octreotide hardens the pancreas. Octreotide pretreatment may therefore be an advantage when performing surgery on a soft pancreas, i.e., in patients scheduled for duodenopancreatectomy for ampullary carcinomas or circumscript pancreatic tumors not associated with chronic pancreatitis.

Animals↗
PubMed2006

[A surgical approach to acute intestinal bleeding].

The estimated incidence of lower gastrointestinal bleeding (LGIB) is 20/100,000 patients per year. Of these cases, 70-80% are minor or stop spontaneously and do not present as emergency hospital admissions. Colonoscopy and angiography detect 80-90% of major LGIB, and subsequent endoscopic intervention or embolisation can control approximately 70%. Emergency surgical intervention is required in haemodynamically unstable patients with persistent bleeding. The surgical treatment of choice is directed to resecting the bleeding bowel segment. Subtotal colectomy is performed in patients with colonic bleeding that can not exactly be localized. Segmental colon resection is often associated with rebleeding and not recommended in this situation. Primary anastomosis can usually be performed; elderly patients in reduced condition, however, are candidates for stoma. In case of persistent or recurrent bleeding and differentiation between intestinal and colonic bleeding fails, loop ileostomy may be performed. If the bleeding appears to originate from somewhere in the small bowel, an additional loop jejunostomy may be performed for specification. The mortality from acute LIGB is approximately 5% but increases with emergency surgery. Risk factors are age, comorbidity, and shock on admission.

Acute Disease↗
PubMed2005

Intensified concurrent chemoradiotherapy with 5-fluorouracil and irinotecan as neoadjuvant treatment in patients with locally advanced rectal cancer.

This study aimed to evaluate the feasibility and efficacy of neoadjuvant chemoradiotherapy intensified with irinotecan in patients with locally advanced rectal cancer. Eligible patients had nonmetastatic disease at a locally advanced stage that made R0 resection and sphincter preservation uncertain. They received preoperative radiation over 6 weeks to 45 Gy and boost of 5.4 Gy and concurrent continuous infusion 5-fluorouracil 250 mg m(-2) day(-1) and weekly irinotecan 40 mg m(-2). In all, 37 patients entered the study. T stage at baseline as determined by ultrasound was T2/T3/T4 in 2/19/16 patients; 31 patients had lymph node involvement. The predominant toxicity was diarrhoea (grade 3/4 in 10/2 patients). Haematologic toxicity and surgical complications were moderate. Among 36 patients undergoing surgery, 32 (89%) had R0 resection and 23 (64%) sphincter preservation. Pathologic complete response (pCR) was achieved in eight (22%) of 36 patients, and 10 patients (28%) had only microscopic residual disease. At 4 years, overall survival was 66%, disease-free survival 73%, local relapse rate 7%, and distant failure rate 24%. Extent of resection and postoperative nodal status were significant predictors of overall and disease-free survival. Intensified neoadjuvant chemoradiotherapy with irinotecan can be safely administered and results in a high pCR rate.

Adenocarcinoma↗
PubMed2002

Temporary unilateral microembolization of the lung-a new approach to regional chemotherapy for pulmonary metastases.

BACKGROUND: Except in patients with resectable disease, treatment of pulmonary metastases is still disappointing. Regional chemotherapy may be a suitable method for delivering more effective doses to regionally confined tumors while minimizing systemic toxicity. We propose an unilateral chemoembolization of the lung applicable by endovascular method. MATERIALS AND METHODS: An unilateral microembolization of the lung with degradable starch microspheres (DSM) alone (group 1) and combined with carboplatin (group 2) was performed on Sprague-Dawley rats (n = 12). Microcirculatory parameters were studied by in vivo videomicroscopy and radiological pattern on pulmonary angiogram. RESULTS: After injection of DSM, mean embolization time in subpleural capillaries was 7.1 +/- 2.3 min, followed by a mean flow retardation of 14.3 +/- 4.6 min; 21.4 +/- 4.7 min after embolization, original flow of erythrocytes was observed demonstrating reperfusion and reversibility of microembolization. After reperfusion relative fluorescence measured in subpleural alveoli was 0.13 +/- 0.049 in group 1, 0.105 +/- 0.016 in group 2, and 0.11 +/- 0.036 in control group (NS). Alveolar septal diameter was 17.3 +/- 1.13 microm in group 1, 16.8 +/- 1.25 microm in group 2, and 16.6 +/- 1.08 microm in control group (NS), demonstrating neither altered permeability nor pulmonary edema. Pulmonary angiogram confirmed patency of the central pulmonary artery. CONCLUSION: For the first time unilateral microembolization of the lung could be established in an experimental model. By injection of DSM, reversible embolization on arteriolar and capillary level could be demonstrated without occlusion of the main branches of the pulmonary arteries. Alveolar-capillary membrane disorder as symptom of early toxicity could not be detected even with additional application of carboplatin.

Animals↗
PubMed2002

Persistent multiple organ microcirculatory disorders in severe acute pancreatitis: experimental findings and clinical implications.

This study characterizes microcirculatory changes (capillary blood flow, capillary permeability, and leukocyte rolling) in the pancreas, colon, liver, and lungs at different stages of severe acute pancreatitis (AP) in a well-established rat model using intravital microscopy and computerized image analysis. The results demonstrate that microcirculatory disorders in severe AP are not confined to the pancreas but can also be found in the colon, liver, and lungs; that they extend beyond the early stage of AP and persist for 48 hr (and longer); and that they not only affect capillary blood flow but also involve prolonged changes of capillary permeability and leukocyte endothelial interaction. These findings may explain previous observations that therapeutic strategies aimed at enhancing microcirculation improve outcome in AP even if therapy is delayed and pancreatic necrosis can no longer be influenced. Since these systemic microcirculatory disturbances may contribute to AP-associated multiple organ dysfunction syndrome, further studies are warranted to evaluate whether improvement of microcirculation stabilizes organ function in AP and how long this may be effective after disease onset.

Acute Disease↗
PubMed2001

An experimental rat model for studying pulmonary microcirculation by in vivo videomicroscopy.

It is unclear what role pulmonary microcirculatory disorders play in the pathogenesis of adult respiratory distress syndrome. The aim of this study was to establish a rat model for the direct visualization of pulmonary microcirculation by in vivo fluorescence videomicroscopy. The pulmonary terminal vascular bed was visualized and the microcirculatory parameters of leukocyte sticking, erythrocyte velocity, capillary permeability, and interalveolar septal diameter were quantified. These parameters were examined simultaneously. The preparation was stable for 120 min. Under hyperthermia, there was increased permeability with a relative fluorescence of 0.39 +/- 0.19 compared to 0.16 +/- 0.13 in the control group, and interalveolar septal diameters were wider (30.7 +/- 2.9 microm) than in control animals (17.3 +/- 3 microm). Under hypothermia and hypovolemia, the erythrocyte velocity was lower (0.351 +/- 0.063 and 0.378 +/- 0.044 mm/s) than in control groups (0.527 +/- 0.07 mm/s). Under hypoventilation, we observed a higher amount of leukocyte sticking (3.1 +/- 1.1 vs 1.8 +/- 0.8 cells/alveolus) and increased permeability (relative fluorescence 1.03 +/- 0.37 vs 0.16 +/- 0.13 in the control group). The model of rat lung exposure for direct examination of microvascular structures in living animals was valuable because it remained stable for 2 h under baseline conditions and demonstrated distinct changes in microcirculatory parameters following specific pathophysiological interventions.

Animals↗
PubMed2001

Changes of colonic mucosal microcirculation and histology in two colitis models: an experimental study using intravital microscopy and a new histological scoring system.

This study investigated capillary blood flow (CBF) and pathomorphological alterations in the mucosa of different bowel segments at different times after disease onset in rats with colitis induced by either trinitrobenzensulfonic acid (TNBS) or mitomycin-C. CBF was determined by intravital microscopy using fluorescein-labeled erythrocytes. The histological degree of inflammation was assessed by a new scoring system. Severe acute histological changes were found in the distal colon 24 hr after induction of TNBS colitis (score: 8.9+/-1.0). CBF was increased (2.9+/-0.05 vs. 2.6+/-0.04 nl/min in healthy controls). The histological alterations persisted until day 3 (8.5+/-0.9) when CBF significantly decreased (1.8+/-0.05 nl/min). After 15 days, moderate acute inflammation was still detectable histologically (5.4+/-1.3), but CBF had returned to normal values. In mitomycin-C colitis, changes developed mainly in the proximal colon: After three days, there was mild inflammation (2.8+/-1.2) with normal CBF (2.5+/-0.1 nl/min). After seven days, the inflammation had increased (4.8+/-1.1), while CBF had decreased (1.5+/-0.06 nl/min). These changes persisted for six weeks (5.3+/-0.7; 1.2+/-0.05 nl/min). These data suggest that disturbed colonic microcirculation may play an important role in the pathogenesis of inflammatory bowel disease regardless of the histopathomorphological alterations.

Animals↗
PubMed2001

[Pancreatitis and nutrition. Significance of the gastrointestinal tract and nutrition for septic complications].

Septic complications are an important factor for the morbidity and mortality of acute pancreatitis. The gut has been identified as a source of infection early in the course of the disease allowing intestinal bacteria to translocate into pancreatic necrosis and other organs. Bacterial translocation is promoted by an impaired intestinal mucosal barrier which can be attributed to the reduced oxygen and substrate supply of the intestine during the early systemic response to the pancreatic injury. A rat model of severe acute pancreatitis has been used to confirm the hypothesis that an impaired mucosal barrier can be stabilized by supplying certain nutritients, vitamins and trace elements. Following a discussion of the many aspects of bacterial translocation and gut derived sepsis, the role of the gut and nutrition for the development of septic complications in acute pancreatitis is summarized as follows: Early in the course of acute pancreatitis the gut is a target organ of the primary systemic inflammatory response (SIRS) to pancreatic injury. SIRS-induced gut barrier dysfunction promoting bacterial translocation makes the gut the motor for secondary (septic) complications. As a septic focus the gut becomes a target for therapeutic measures aimed at stabilizing the impaired gut barrier. Nutritive factors demonstrated to improve impaired gut barrier function include early enteral feeding and specific factors like glutamine which are essential for enterocytes and colonocytes in stress. Experimental data are presented to underline the significance of these nutritive factors and subsequent randomized multicenter trials performed to verify the positive experimental results are introduced. The effect of other nutritive factors (e.g. omega-3-fatty acids) has not yet been systemically investigated. Thus, experimental and clinical studies need to be performed for evaluating their effect on bacterial translocation and the disease course in acute pancreatitis.

Animals↗
PubMed2001

An improved clinical model of orthotopic pancreatic cancer in immunocompetent Lewis rats.

The study of pancreatic cancer (PaCa) requires orthotopic, clinically relevant animal models. The aims of this study were to establish an orthotopic model of ductal pancreatic adenocarcinoma in immunocompetent Lewis rats and to develop a scoring system to quantify local tumor infiltration and distant metastasis. Cells (10(7)) of the rat ductal PaCa cell line DSL-6A/C1 were injected s.c. into donor rats. After 8 weeks, either three (IPL-3) or five (IPL-5) fragments (1 mm3) of the resulting s.c. tumors were microsurgically implanted into the pancreas of recipient rats. In another series of animals, 10(7) DSL-6A/C1 cells were directly injected (INJ) into the pancreas. All animals were monitored daily until death or for 16 weeks. At autopsy, volume of primary tumors and ascites, local and systemic tumor spread, and histologic phenotype were assessed. IPL-5 resulted in significantly larger tumors (12,224 +/- 1,933 mm3), more local infiltration and systemic spread (score: 18.3 +/- 2.0 points), severe clinical tumor disease, and lethality (50%) in comparison to the other induction techniques (IPL-3: 283 +/- 115 mm3/3.5 +/- 0.8 points/0; INJ: 752 +/- 207 mm3/4.3 +/- 0.8 points/8%). Histologic examination revealed moderately to well-differentiated ductal tumors, surrounded by dense stroma. Intraperitoneal tumor dissemination in the INJ group occurred simultaneous with primary tumor growth, indicating PaCa cell spread during injection. Orthotopic implantation of five DSL-6A/C1 tumor fragments into the rat pancreas provides a valid clinical model of ductal pancreatic adenocarcinoma in immunocompetent rodents for preclinical treatment studies. The dissemination score we used permitted quantification of local and systemic tumor spread.

Adenocarcinoma↗
PubMed2001

Endothelin mediates local and systemic disease sequelae in severe experimental pancreatitis.

Endothelin-1 has been shown to reduce pancreatic blood flow and cause focal acinar cell necrosis similar to those seen in acute pancreatitis (AP), whereas therapy with endothelin receptor antagonists enhanced pancreatic capillary blood flow (PCBF) and decreased mortality rates. The current study evaluated the role of endothelin in the development of severe AP. Trypsinogen activation peptides, acinar cell necrosis, and PCBF were used as local indicators of disease severity, fluid sequestration, cardiorespiratory and renal parameters, and colonic capillary blood flow as systemic disease indicators. The following groups of animals were examined: 1) rats with mild edematous AP and 2) severe necrotizing AP treated with and without endothelin, 3) transgenic rats overexpressing endothelin with severe AP, and 4) rats with severe AP prophylactically treated with endothelin receptor antagonists. The following observations were made: endothelin superimposed on mild AP caused hemoconcentration, a decrease in PCBF, and necrosis and ascites not seen in this model without endothelin exposure. Endothelin superimposed on severe AP had no significant effects. After induction of severe AP, less PCBF and more acinar cell necrosis were observed in transgenic rats than in their normal littermates. Prophylactic endothelin receptor antagonists improved local (acinar necrosis, PCBF) and systemic parameters (ascites, urine production, colonic capillary blood flow) of disease severity in animals with severe AP. These observations underscore the role of endothelin as a mediator of disease severity in AP and suggest that endothelin receptor blockade may become a promising therapeutic tool in this disease.

Acute Disease↗
PubMed2000

Experimental models of acute pancreatitis: are they suitable for evaluating therapy?

Since randomized controlled studies of severe acute human pancreatitis can be performed only with restrictions, at least some aspects of innovative therapy concepts should first be clarified in animal experiments. In vitro trials are inadequate for this purpose since they cannot simulate the complex course of severe acute pancreatitis. Animal test results can be transferred to clinical practice if the results are based on trials with established models, standardized methods, and a study design imitating the clinical situation. This contribution discusses the demands on such an animal model of acute pancreatitis and a corresponding study protocol and presents models and protocols which meet these requirements. Concrete examples are presented to show that animal experiments are of great value under these conditions, especially in acute necrotizing pancreatitis. Further standardization of models, protocols, and monitoring should further improve future animal therapy studies at least to the extent that it is possible to select particularly promising substances, which should then be tested in randomized controlled trials.

Acute Disease↗
PubMed2000

Animal models of exocrine pancreatic cancer.

Clinically and biologically relevant animal models are mandatory to further evaluate both the pathophysiology and novel strategies for diagnosis and treatment of exocrine pancreatic cancer. This review briefly summarizes the features of human pancreatic cancer in order to define requirements for animal models of the disease. The described model systems in rodents include pancreatic cancer induced by chemicals, pancreatic cancer in transgenic, and immunodeficient animals.

Animals↗
PubMed2000

Endothelin receptor blockade in severe acute pancreatitis leads to systemic enhancement of microcirculation, stabilization of capillary permeability, and improved survival rates.

BACKGROUND: We previously demonstrated that therapy with a new endothelin A receptor antagonist (ET-RA) significantly reduced mortality rates in severe acute pancreatitis (AP) in the rat without attenuating local signs of disease severity (intrapancreatic protease activation, acinar cell necrosis). This raised the question as to why ET-RA was so effective. The purpose of this study was to assess the effect of ET-RA on microcirculation (particularly capillary permeability) within and outside of the pancreas on intravascular fluid loss and extravascular fluid sequestration and on distant organ function. METHODS: Severe AP was induced in rats by standardized intraductal bile acid infusion and cerulein hyper-stimulation. Starting 6 hours (n = 24 rats) and 12 hours (n = 30 rats) after the onset of AP, animals randomly received either the ET-RA (LU-135252) or saline solution with fluid resuscitation (6 mL/kg/h Ringer's lactate). At 24 hours, animals were relaparotomized for intravital microscopic determination of capillary blood flow, leukocyte rolling, and capillary permeability in the pancreas and colon. Further monitoring included cardiorespiratory and renal parameters, hematocrit levels and quantification of ascites and pleural effusions, and acinar cell necrosis at autopsy. Groups of sham-operated healthy animals (n = 6 animals each) that had been treated according to the same protocol served as control animals. RESULTS: ET-RA treatment that was started 6 hours after AP-induction significantly decreased hematocrit levels (38% +/- 1% vs 45% +/- 2% with saline solution treatment), reduced ascites and pleural effusions (6.7 +/- 1.3 mL vs 11.9 +/- 1.3 mL), and improved urine production (4.8 +/- 0.5 mL vs 2.9 +/- 0.6 mL) and respiratory parameters. Moreover, all microcirculatory parameters were improved; in particular, capillary permeability was stabilized (158% +/- 9% vs 248% +/- 8% in the colon). These beneficial effects were also seen when therapy was delayed until 12 hours after AP induction. Pancreatic necrosis was not significantly reduced. The overall mortality rate was 12% in ET-RA-treated animals and 42% in saline solution-treated control animals (P <.05). In healthy animals ET-RA did not significantly alter the target parameters, except for a reduction of capillary permeability in the pancreas. CONCLUSIONS: Improved microcirculation and stabilized capillary permeability in ET-RA-treated animals together with reduced intravascular fluid loss and extravascular fluid sequestration and improved renal and pulmonary function (1) may explain improved survival in this model, (2) support the hypothesis that systemic disease sequelae significantly contribute to outcome in AP, and (3) suggest that ET-RA may be a promising therapeutic tool in AP because it counteracts microcirculatory disorders that contribute to pancreatitis-associated organ dysfunction even when therapy is delayed to a point at which pancreatic injury may no longer be influenced.

Acute Disease↗
PubMed2000

Effect of endothelin and endothelin receptor blockade on capillary permeability in experimental pancreatitis.

BACKGROUND: Capillary leakage with fluid loss into the third space contributes to many of the early systemic complications in severe acute pancreatitis. There has been increasing interest in endothelin as one of the factors affecting capillary permeability. AIM: To elucidate further the role of endothelin in the development of capillary leakage in acute pancreatitis by investigating the effect of exogenous endothelin administration and endothelin receptor blockade in sham operated animals and two models of acute pancreatitis. METHODS: Determination of capillary permeability in the pancreas and colonic mucosa by quantifying extravasation of fluorescein labelled dextran using a novel computer assisted video image analysis system. RESULTS: Pancreatic and colonic capillary permeability increased stepwise from mild to severe acute pancreatitis. Endothelin increased pancreatic and colonic capillary permeability in healthy animals and animals with mild acute pancreatitis but had no additional adverse effect in severe acute pancreatitis. Endothelin receptor blockade decreased pancreatic capillary permeability in sham operated rats but had no effect on the colon. In mild and severe acute pancreatitis, endothelin receptor blockade stabilised increased capillary permeability in both the pancreas and colon. CONCLUSIONS: Endothelin plays an important role in mediating capillary permeability in the pancreas. In severe pancreatitis, it increases capillary permeability even outside the pancreas, thereby contributing to capillary leakage. Endothelin receptor blockade significantly reduces capillary permeability in acute pancreatitis both in and outside the pancreas, suggesting a therapeutic approach to counteract capillary leakage in severe acute pancreatitis.

Animals↗
PubMed2000

Effect of fluid resuscitation with and without endothelin A receptor blockade on hemoconcentration and organ function in experimental pancreatitis.

BACKGROUND: Intravascular fluid loss contributes to pancreatitis-associated multiple organ dysfunction and is thus a major target for therapy in this life-threatening disease. AIM: To evaluate intravascular fluid loss and extravascular fluid sequestration together with cardiorespiratory and renal function in a well-established rat model of severe acute pancreatitis (AP) and to investigate the effect of fluid resuscitation with and without endothelin receptor A blockade on these parameters. METHOD: Induction of AP in rats by a standardized bile salt infusion into the pancreatic duct and intravenous cerulein hyperstimulation. Six hours after AP induction, animals were randomized into 4 groups to receive (1) no therapy; (2) 4 ml/kg/h Ringer's lactate (RL) i.v.; (3) 8 ml/kg/h RL i.v., or (4) 4 ml/kg/h RL plus an endothelin receptor antagonist. Target parameters measured before and after AP induction and during the 24-hour observation period included: mean arterial blood pressure, heart rate, hematocrit, arterial blood gases, urine production, ascites and pleural effusions. RESULTS: After 6 h, all animals presented with severe hemoconcentration (hematocrit >57%) and oliguria (<0.5 ml/6 h). Cardiorespiratory parameters were within the normal range. Up to 12 h after AP induction, animals without therapy had an increased hematocrit and oliguria and developed metabolic acidosis. Animals receiving fluid resuscitation had a significant drop in hematocrit and maintained compensated blood gas values. A significant increase in urine production was only observed in animals given 8 mg/kg/h RL. Between 12 and 24 h, urine production significantly increased with fluid resuscitation and respiratory parameters stabilized except for animals treated with 8 ml/kg/h RL which developed arterial hypoxia and hypercapnia. CONCLUSIONS: Intravascular fluid loss and extravascular fluid sequestration together with decreased urine production characterize the early phase of this model of severe AP. Massive fluid resuscitation necessary for increasing urine output may lead to respiratory distress. Reduction of intravascular fluid loss by endothelin receptor blockade is associated with improved renal and respiratory function.

Acute Disease↗