Hepatic arterial infusion (HAI) with PEGylated liposomes containing 5-FU improves tumor control of liver metastases in a rat model.

PURPOSE: To investigate the cytostatic effect of 5-fluorouracil (5-FU) encapsulated in polyethylene glycol (PEG) liposomes with or without degradable starch microspheres (DSM) in a long-term trial using a rat liver tumor model. MATERIALS AND METHODS: The cytostatics were applied once either as a hepatic arterial infusion (HAI) or were systemically infused via the tail vein. Seven groups were compared with respect to tumor growth and survival times: 5-FU HAI (group I), 5-FU + DSM HAI (group II), PEG-5-FU HAI (group III), PEG-5-FU + DSM HAI (group IV), NaCl HAI (group V), 5-FU i.v. (group VI), and PEG-5-FU i.v. (group VII). RESULTS: Seven and 14 days after treatment in groups III and IV, only group IV had significantly inhibited tumor growth on day 21 compared to the groups treated intravenously. On day 28, none of the animals from the intravenously treated groups were still alive compared to a significantly longer survival time of 6 and 8 weeks in groups III and IV. CONCLUSION: Locoregional therapy with 5-fluorouracil encapsulated in PEGylated liposomes may further improve the treatment success with longer-lasting tumor regression and prolonged survival times.

Bowel perforation in non-small cell lung cancer after bevacizumab therapy.

BACKGROUND: Bevacizumab is increasingly used in combination with chemotherapy for treatment of unresectable non-small cell lung cancer. The aim of this report is to underline possible risks associated with this otherwise well-tolerated drug. PATIENT: A 69-year-old patient with metastatic non-small cell lung cancer was started on a palliative chemotherapy regimen containing carboplatin, paclitaxel, and bevacizumab. RESULTS: After the second cycle of chemotherapy, the patient developed abdominal pain. On emergency laparotomy, there was diffuse perforation of the colonic wall, so the patient underwent a Hartmann's procedure with subtotal colectomy. Histopathological examination confirmed the diagnosis of ischemic colitis. CONCLUSION: Gastrointestinal perforation is a known adverse event of bevacizumab therapy which so far has occurred only in patients with predisposing risk factors. Our patient illustrates that there must always remain a high index of suspicion regarding bowel perforation in patients developing acute abdominal pain under bevacizumab therapy, even if they have no apparent risk factors.

Chemoembolization with carboplatin of the lung. Feasibility and toxicity in a pig model.

OBJECTIVES: Chemoembolization of the lung was evaluated as a novel treatment for unresectable lung metastases. Based on our encouraging results in a rodent model (rat), the aim was to prove the safety and effectiveness of this novel method in a large animal model before clinical application of this therapy. MATERIALS AND METHODS: Eight pigs underwent femoral vein puncture. The tumor-supplying pulmonary arteries were selectively explored and chemoembolization with degradable starch microspheres (DSM) and carboplatin was administered. Survival, hemodynamic parameters, ventilation gas exchange, digital subtraction angiography (DSA) and pulmonary X-rays were documented during and after chemoembolization. As a follow-up, a pulmonary X-ray was assessed every week for six months after chemoembolization when the animals were sacrificed and the lungs histologically examined. RESULTS: Selective and reversible chemoembolization of the right lung was recorded by DSA. Only slight hemodynamic effects were seen during selective chemoembolization of the lung. X-ray examinations showed no early or late abnormalities. The histological examination of the lung tissue six months after chemoembolization showed that the parenchyma was normal. CONCLUSION: This is the first study of chemoembolization of the lung in a large animal model. The feasibility, mild hemodynamic acute effects and the absence of long-term toxicity were documented. These observations justify patient studies in unresectable lung metastases.

Chemoembolization of lung metastases--pharmacokinetic behaviour of carboplatin in a rat model.

AIM: To improve tumor control in lung metastases using a novel method: unilateral chemoembolization of the lung by instillation of degradable starch microspheres (DSM) and cytotoxic agents via the pulmonal artery. MATERIALS AND METHODS: A rodent model of solitary metastasis (CC531 adenocarcinoma) was studied. The animals were randomized into three groups: the control group receiving carboplatin (45 mg/kg) intravenously, an isolated lung perfusion (ILP) group recieving buffered starch solution and carboplatin (15 mg/kg) and a third group receiving chemoembolization with carboplatin (15 mg/kg) and DSM (2 ml/kg). The total platinum concentration in serum, lung and lung tumor at defined times (15, 30, 60, 120 min) was measured using an inductively coupled plasma mass spectrometer (ICP-MS). RESULTS: The area under concentration (AUC) versus time curves showed a 7.9- to 42.6-fold higher concentration in the tumor tissue comparing the ILP and chemoembolization group to the control group (p < 0.01). In the comparison of the AUCs of ILP versus chemoembolization, the tumor tissue of the lung showed a 5.4-fold higher concentration in the chemoembolization group (p < 0.01). CONCLUSION: This is the first study to measure the concentration of carboplatin during chemoembolization of the lung. Compared to intravenous therapy, chemoembolization produced higher tumor tissue concentrations. Comparing chemoembolization to ILP, there was also an increase of carboplatin in the tumor tissue, without histological damage of the surrounding lung parenchyma.

Anastomotic stability and wound healing of colorectal anastomoses sealed and sutured with a collagen fleece in a rat peritonitis model.

BACKGROUND/OBJECTIVE: Anastomotic insufficiency is associated with increased morbidity and mortality. A collagen fleece that supports anastomosis is effective for preventing anastomosis insufficiency. The objective of this study was to compare between the stability of sutured anastomoses and that of anastomoses sealed with a thrombin/fibrinogen-coated collagen fleece in a rat peritonitis model. METHODS: In 72 male Wistar rats, peritonitis was induced with a specially prepared human fecal solution. Surgery at the rectosigmoid junction was performed 24-36 hours later. The different anastomotic techniques used were circular sutured anastomoses, semicircular sutured anastomosis and closure of the anterior wall with collagen patch, and complete closure with a collagen fleece. Bursting pressure, histology of anastomosis, mRNA expression of collagen types I and III, matrix metalloproteinase-13, and vascular endothelial growth factor (VEGF) were investigated after 24 hours, 72 hours, and 120 hours. RESULTS: All animals developed peritonitis of comparable severity. There were no differences in bursting pressures between the three suture techniques after 24 hours, 72 hours, or 120 hours. Anastomoses sealed with a collagen fleece appeared to be slightly less stable only at 24 hours, whereas they appeared to be more stable than semisutured or fully sutured anastomoses at 72 hours and 120 hours. Sealing with a collagen fleece was associated with an increase in granulation tissue, higher mRNA levels for collagen types I and III, and higher VEGF compared to sutured anastomoses. CONCLUSION: The use of a thrombin/fibrinogen-coated collagen fleece showed similar efficacy to conventional sutures in colorectal anastomoses in the presence of peritonitis inflammation, and may provide additional benefits due to an increase in mature granulation tissue.

Risk factors for clinical anastomotic leakage and postoperative mortality in elective surgery for rectal cancer.

BACKGROUND AND AIMS: Clinical anastomotic leakage remains a major problem after anterior or low anterior resection for rectal cancer. The aim of this study was to assess the association between risk factors and anastomotic leakage and postoperative mortality. MATERIALS AND METHODS: Two hundred seventy-six elective anterior or low anterior resections with anastomosis were performed and documented on-line from January 1995 to December 2004. Univariate and multivariate analyses with Bonferroni adjustment were carried out to identify relevant risk factors. RESULTS: The rate of anastomotic leakage was 14.9% (41 of 276 patients) with a mortality of 12.2% (5 of 41 patients). Overall mortality was 2.5% (7 of 276 patients). Multiple regression analysis showed that smokers had an increased risk of anastomotic leakage [odds ratio (OR), 6.42; 95% confidence interval (CI), 2.68-15.36] as well as patients with coronary heart disease (OR, 7.79; 95% CI, 2.52-24.08). Smokers (OR, 13.20; 95% CI, 2.48-7.24) and patients with coronary heart disease (OR, 23.46; 95% CI, 4.33-27.04) also had an increased risk of postoperative mortality in the univariate analysis as well as patients with anastomotic leakage (OR, 16.25; 95% CI, 3.04-16.92). CONCLUSIONS: Smoking and coronary heart disease are important risk factors for anastomotic leakage and postoperative mortality after elective resection for rectal cancer.