Uwe Pohlen

Diagnostics and surgical treatment strategy for rectal cavernous hemangiomas based on three case examples

Abstract A 20-year-old man with a congenital vascular malformation extending from the anal canal into the distal sigmoid had had recurrent perianal blood loss as a neonate. A hemangioma was diagnosed for the first time in 1978. The patient received regular and frequent gastroenterological treatment until admission. Decisive for the indication for surgery was the patient’s need for blood infusions and shorter bleeding intervals in June 1998. Surgical therapy consisted of deep anterior rectosigmoid resection with coloanal pouch anastomosis. In a second case of a 27-year-old woman a sigmoid hemangioma was diagnosed in conjunction with emergency sigmoid resectioning. Because of recurrent hemorrhages a coloanal pouch was also established here in a second step. The third case involved a 19-year-old woman with a 12-year history of repeated perianal hemorrhages. After sigmoid discontinuity resection we carried out proctectomy with descendostoma creation due to renewed severe intractable perianal bleeding. The histological examination revealed a rectal hemangioma that had caused the repeated perianal hemorrhages. Surgical reconstruction was then achieved by coloanal pouch anastomosis. In view of the good functional and perioperative results, current surgical therapy should aim at preserving continuity and continence by coloanal pouch anastomosis.

Improvement in 5-Fluorouracil (5-FU) and 5-Fluoro-2'- Deoxyuridine (FdUrd) Concentration by 5-Fluorouracil- Polyethylene-Glycol-Liposomes in Abdominal Stop-Flow: Treatment of VX2 Liver-Tumor-Bearing Rabbits

Abstract The application of liposome-encapsulated cytostatics results in higher concentrations in tumor tissue. This effect can be further increased by blood flow retardation with longer retention time in the tumor and by arterial administration. In abdominal stop-flow therapy, a separate partial circulation with a defined flow is realized via a roller pump under hypoxic conditions. Forty chinchilla rabbits with VX-2 liver tumors were treated either intra-aortally (stop-flow therapy) or systemically with 50 mg 5-FU or 5-FU-PEG liposomes. During therapy, pH and pO2 were measured at regular intervals. After 20 minutes, concentrations of 5-FU and its metabolite FdUrd were determined by HPLC in different organs and the liver tumor. Compared to the i.v. application of monosubstances, the combination of i.a. 5-FU-PEG liposomes and flow retardation increased the concentration in tumor tissue by a factor of 44 and even 100-fold in the para-aortal lymph nodes (LN). The concentration of 5-FU and FdUrd was increased by flow reduction, intraaortal application and liposomal encapsulation of 5-FU.

Intra-aortal therapy with 5-fluorouracil-polyethylene glycol stealth liposomes: Does the metabolism of 5-fluorouracil into 5-fluoro-2'-deoxyuridine depend on pH value? An animal study in VX-2 liver tumor-bearing rabbits

Background: The application of liposome-encapsulated cytostatics results in higher concentrations in tumor tissue. This effect can be further increased by blood flow retardation with longer retention time in the tumor and by arterial administration realized in abdominal stop-flow therapy, a separate partial circulation with a defined flow under hypoxic conditions. The pH changes under stop-flow therapy may affect the further metabolism of 5-fluorouracil (5-FU), used here. Methods: The in vitro 5-fluoro-2′-deoxyuridine (5-FUrd) concentrations at increasing pH values were measured using liposomal encapsulated and free 5-FU. Subsequently, 20 chinchilla rabbits were treated intra-aortally with 5-FU or 5-FU-polyethylene glycol (PEG) liposomes. The pH value was maintained in the physiological range by continuous NaHCO3 application. After 20 min, concentrations of 5-FU and its metabolite 5-FUrd were determined in different organs, the perfusate, serum and the VX-2 tumor by HPLC. Results: The in vitro 5-FUrd concentrations, which occur only in the physiological pH range, were doubled by the use of 5-FU-PEG liposomes. In the animal trial, NaHCO3 titration doubled the 5-FUrd concentrations found in our preliminary studies. Compared to free 5-FU, 5-FU-PEG liposomes significantly increased the concentrations in the VX-2 liver tumor by 6.6-fold and in the para-aortal lymph nodes by 8.76-fold. Conclusion: The metabolism of 5-FU into its active metabolite 5-FUrd depends on the pH value and can be modulated. 5-FUrd concentrations can be approximately doubled with the intra-aortal application of 5-FU-PEG liposomes compared to free 5-FU.

Improved Tumor Targeting by Regional Carboplatin Application Combined with Gelfoam

Regional chemotherapy of liver metastases is a promising alternative to systemic chemotherapy. Despite a number of theoretical advantages, extended life expectancy has only been confirmed in two studies. Since tumors have a concentration-dependent response to cytostatics, the primary goal is to increase the cytostatic concentration applied in tumor tissue. The aim of this study on liver tumor-bearing chinchilla rabbits was to show that the regional application of carboplatin leads to an increased concentration in tumor tissue. A further increase in carboplatin concentration by additional regional application of gelatine powder (Gelfoam®) was demonstrated in a subsequent test; regional compared to intravenous application increased the carboplatin concentration in the tumor tissue by a factor of 12.1 and coapplication with Gelfoam increased the cytostatic concentration by a factor of 44.3.

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.

Morbidity and mortality of elderly patients after surgery of liver metastases

Introduction and oblective: Colorectal carcinomas are the second most common cause of death irt western industrialized natiorks Liver metastases develop in 50% of the patients. About 5% of the population is >75 years Thus, the question increasingly arises as to whether an elderly patient should undergo liver resection. The aim of this study was to compare the nmrNdity, mortality and survival of patmnts >75 years to that of patients 75 years and 137 (67%) 75 years with a mortal W of 5% and a major morbidity of 10% There was no sigmflcant difference between the morbidity, mortality and survival of patients 75 years

Dünndarminvagination beim Erwachsenen

Die Diagnose Dunndarminvagination beim Erwachsenen ist im Gegensatz zur kindlichen, eine seltene Diagnose. Haufig geht das Krankheitsbild mit einem langsam schleichenden Verlauf einher, es kann sich auch als akutes Abdomen darstellen. Wir berichten uber 3 Patienten mit Dunndarminvagination und akutem Abdomen. In 2 Fallen fuhrte die Computertomographie zur Diagnose einer Invagination des Dunndarms. In 1 Fall wurde die Patientin koloskopiert und hierbei die Invagination des terminalen Ileums gesehen. Bei allen Patienten erfolgte ein sofortiger operativer Eingriff mit sparsamer Segmentresektion und End-zu-End-Anastomose. In allen 3 Fallen war die Invagination durch eine pathologische, benigne Veranderung hervorgerufen. Die Dunndarminvagination des Erwachsenen muss immer chirurgisch angegangen werden. In uber 95% der Falle findet sich intraoperativ ein pathologischer Befund, der im Dunndarm wiederum zu 85–95% benigne ist.

Intravitalmikroskopische und pharmakokinetische Untersuchung zur Anreicherung von 5-FU-PEG-Liposomen sowie dynamisches MRT-Monitoring des Langzeitverlaufs an CC-531 lebertumortragenden WAG-Ratten

Controversy still exists for therapy of inoperable colorectal liver metastases. Regional therapy has been considered a promising approach because several clinical studies demonstrated prolonged survival. The aim of this study was to investigate tumor targeting of the most frequently used cytostatic 5-fluouracil by modifying systemic and regional therapy by liposome encapsulation. Our results demonstrate that encapsulation of 5-FU in SUV-PEG liposomes increased tumor concentration by the factor 25 fold with systemic and factor 85 with regional therapy. Reduction of blood flow by starch microspheres (SMS) during regional chemotherapy with liposome-encapsuled 5-FU resulted in an additional 4000 fold increase in 5-FU tumor concentration.