Transvaginal Hybrid NOTES Cholecystectomy: A Single-Centre Long-Term Experience on Sexual Function.

INTRODUCTION: Transvaginal hybrid NOTES cholecystectomy is an alternative approach to the traditional laparoscopic technique. Despite increasing data regarding clinical outcomes following transvaginal hybrid NOTES cholecystectomy, there is still a lack of long-term results, particularly with regard to sexual function. Therefore, the aim of this study was to evaluate long-term outcome of a series of transvaginal hybrid cholecystectomy. PATIENTS AND METHODS: Female patients with symptomatic cholecystolithiasis who underwent transvaginal hybrid NOTES cholecystectomy were retrospectively analysed regarding clinical and surgical outcome parameters. Furthermore, all patients received a 17-question survey postoperative with questions about sexual intercourse, the domains satisfaction and pain of the German Female Sexual Function Index. RESULTS: Overall, 47 of 80 patients were included in the study with a completed survey responses (return rate 58.6%), with a mean age of 48 years, mean body mass index of 29 and mean operative time of 47 min. The median follow-up was 40 months. There were no intra- or postoperative complications and no conversion to a laparoscopic or open approach. No significant differences were found for postoperative sexual function (painful intercourse, inability to achieve orgasm), although sexual intercourse was less frequent postoperatively (p = 0.022). Forty-four patients (93.7%) were satisfied with the aesthetic and the overall postoperative result, and 40 patients (85.1%) would recommend the applied surgical technique to friends and family. CONCLUSION: The findings show that transvaginal hybrid NOTES cholecystectomy is a safe procedure for female patients, particularly with regard to sexual function.

Therapy of complicated Crohn's disease during pregnancy--an interdisciplinary challenge.

BACKGROUND: Severe courses of Crohn's disease (CD) during pregnancy are rare. However, if occurring, the risk of miscarriage and low birth weight is increased. At present, only limited data is available on the treatment of CD during pregnancy. In particular, there are no standard guidelines for surgical therapy. Nevertheless, surgery is often unavoidable if complications during the course of the disease arise. PURPOSE: This study provides a critical overview of conventional and interventional treatment options for CD complications during pregnancy and analyses the surgical experience gained thus far. For illustrative purposes, clinical cases of three young women with a severe clinical course during pregnancy are presented. METHODS: After treatment-refractory for conservative and interventional measures, surgery remained as the only treatment option. In all cases, a split stoma was created after resection to avoid anastomotic leaks that would endanger the lives of mother and child. The postoperative course of all three patients was uneventful, and pregnancy remained intact until delivery. No further CD specific medication was required before birth. CONCLUSIONS: The management of CD patients during pregnancy requires close interdisciplinary co-operation between gastroenterologists, obstetricians, anaesthetists and visceral surgeons. For the protection of mother and child treatment should thus be delivered in a specialised centre. This article demonstrates the advantages of surgical therapy by focusing on alleviating CD complaints and preventing postoperative complications.

The application of TachoSil® for sealing colorectal anastomosis: a feasibility study.

AIM: Anastomotic leakage is a frequent postoperative complication of colorectal resection. This nonrandomized study assessed the feasibility and safety of applying a haemostatic tissue sealant (TachoSil®) to colorectal anastomoses following resection. METHOD: TachoSil was applied as reinforcement of the anastomotic line after laparoscopic or open colorectal resection. The primary endpoint was the proportion of patients for whom TachoSil application was considered feasible by both the investigator and an independent external assessor. Application was considered feasible if TachoSil fully adhered, covered ≥1cm beyond the margin of the anastomotic line and patches overlapped by ≥1cm. Individual investigator assessment of feasibility and adverse events 30 days after surgery were also recorded. RESULTS: Twenty-five patients underwent anterior resection (seven open lower, nine open middle-upper, four laparoscopic lower and five laparoscopic middle-upper). In six cases a video-recording was not available because of technical problems. The primary endpoint was met in 12 of the remaining 19 patients (63%; 95% CI 38-84%), while in the other seven the application was recorded as not feasible because the assessor was unable to see the entire anastomosis. No application was assessed as unfeasible on the basis of visual evidence. When assessed by the investigator alone, TachoSil was considered feasible in all but one instance (96%; 95% CI 80-100%). There were 45 adverse events, of which 10 were serious. None was considered related to TachoSil. No deaths were reported. CONCLUSION: Application of TachoSil to reinforce the anastomotic line in colorectal resections appears to be feasible and well tolerated.

[Simulation training in surgical education - application of virtual reality laparoscopic simulators in a surgical skills course]. / Simulationstraining in der Weiterbildung - Einsatz von virtuellen laparoskopischen Operationssimulatoren in einem chirurgischen Trainingskurs.

BACKGROUND: Training and simulation are gaining importance in surgical education. Today, virtual reality surgery simulators provide sophisticated laparoscopic training scenarios and offer detailed assessment methods. This also makes simulators interesting for the application in surgical skills courses. The aim of the current study was to assess the suitability of a virtual surgery simulator for training and assessment in an established surgical training course. MATERIALS AND METHODS: The study was conducted during the annual "Practical Course for Visceral Surgery" (Warnemuende, Germany). 36 of 108 course participants were assigned at random for the study. Training was conducted in 15 sessions over 5 days with 4 identical virtual surgery simulators (LapSim) and 2 standardised training tasks. The simulator measured 16 individual parameters and calculated 2 scores. Questionnaires were used to assess the test persons' laparoscopic experience, their training situation and the acceptance of the simulator training. Data were analysed with non-parametric tests. A subgroup analysis for laparoscopic experience was conducted in order to assess the simulator's construct validity and assessment capabilities. RESULTS: Median age was 32 (27 - 41) years; median professional experience was 3 (1 - 11) years. Typical laparoscopic learning curves with initial significant improvements and a subsequent plateau phase were measured over 5 days. The individual training sessions exhibited a rhythmic variability in the training results. A shorter night's sleep led to a marked drop in performance. The participants' different experience levels could clearly be discriminated ( ≤ 20 vs. > 20 laparoscopic operations; p ≤ 0.001). The questionnaire showed that the majority of the participants had limited training opportunities in their hospitals. The simulator training was very well accepted. However, the participants severely misjudged the real costs of the simulators that were used. CONCLUSIONS: The learning curve on the simulator was successfully mastered during the course. Construct validity could be demonstrated within the course setting. The simulator's assessment system can be of value for the assessment of laparoscopic training performance within surgical skills courses. Acceptance of the simulator training is high. However, simulators are currently too expensive to be used within a large training course.

Phase II study of regional chemotherapy using the hypoxic abdominal perfusion technique in advanced abdominal carcinoma. 5-FU pharmacokinetics, complications and outcome.

UNLABELLED: The aim of this study was to verify the rationale of a hypoxic abdominal perfusion (HAP) technique for the perfusion of 5-FU, mitomycin C and cisplatin in patients with inoperable, recurrent abdominal cancer. PATIENTS AND METHODS: In a phase II study, 59 patients with various non-resectable abdominal tumours were treated with 102 perfusions by the HAP-technique. The HAP-technique was performed by using double-balloon arterial-venous catheters that selectively isolated the abdominal vascular section and perfusion was provided by an extracorporal pump for 20 min. Thirty-four patients with unresectable colorectal cancer, 11 with unresectable gastric cancer, eight with unresectable pancreatic cancer and six with cancer of the gall bladder were included. They were treated with a combination of 5-fluorouracil (5-FU 1 g/m(2)), mitomycin C (MMC, 10 mg/m(2)) plus cisplatin (50 mg/m(2)) infused into the isolated abdominal compartment. The cytostatic concentration of 5-FU was determined intrainterventionally within the systemic and regional compartment. Toxicity- and procedure-related complications were documented. Tumour responses were assessed by computer tomography. RESULTS: 5-FU concentration was 16.3-fold higher within the regional compared to the systemic compartment at its maximum, and the area under the curve (AUC) was 7.9 times larger. During the procedure two major complications were experienced (1x perforation of the A. iliaca, lx deep vein thrombosis), no deaths occurred during surgery or in the postoperative period. Minimal systemic and local toxicities were observed (WHO grade III-IV 1%, grade I-II 33%). No complete response but 22 partial responses were observed. Median survival was 15.5 months for colorectal cancer, 12. 5 months for gastric cancer, 12.7 months for pancreatic cancer and 7.8 months for gall bladder cancer. CONCLUSION: The hypoxic abdominal perfusion is a safe and effective palliative treatment for patients with unresectable advanced colorectal, gastric and pancreatic carcinoma. The HAP has not shown promising results for advanced gall bladder cancer. These encouraging clinical results require further evaluation.

Hepatic arterial infusion (HAI). Comparison of 5-fluorouracil, folinic acid, interferon alpha-2b and degradable starch microspheres versus 5-fluorouracil and folinic acid in patients with non-resectable colorectal liver metastases.

BACKGROUND: The prognosis of patients with advanced colorectal tumor is poor. Therefore, other therapy regimes for non-resectable hepatic metastases are necessary. In this prospective study, two regional chemotherapy protocols were compared. PATIENTS AND METHODS: An arterial port system was implanted in 64 patients. Sixty patients were assigned to the two therapy protocols for hepatic arterial infusion (HAI): protocol A (n=24): 5-FU/FA (300 mg/m2 folinic acid and 600 mg/m2 5-fluorouracil daily for 5 days with a 14-day interval); protocol B (n=36): 5-FU/FA/IFN/DSM (450 mg starch microspheres (DSM) with 5 million IU recombinant interferon (IFN), alpha 2b 500 mg/m2 FA and 600 mg/m2 5-FU). RESULTS: The response rate was 50% in protocol A patients and 69.4% in protocol B. The median times for disease progression were 11 months for protocol A and 20 months for protocol B (p = 0.038), while median survival times of 14 months and 26 months, respectively, were obtained (p = 0.015). There were no significant differences in terms of toxic side-effects. Major toxicity problems were observed in 12% of the protocol A-treated patients and in 11% of the protocol B-treated patients. CONCLUSION: Combination therapy with HAI-5-FU/FA/IFN/DSM was superior to HAI-5FU/FA, with a high response rate (69% vs. 55%) and few toxic side-effects. These findings suggest that these combinations should be evaluated in larger studies as first- or second-line therapy in patients with hepatic metastases of colorectal cancer.

Evaluation of efficient chemoembolization mixtures by magnetic resonance imaging therapy monitoring: an experimental study on the VX2 tumor in the rabbit liver.

To find effective chemoembolization mixtures, we tested combinations of carboplatin with the embolizates Spherex and Gelfoam in comparison to a therapy with NaCl-solution, a treatment with the cytostatic drug only, and a therapy with each of the embolizates alone. The experiments were carried out using as a model the VX2 tumor in the liver of male chinchilla rabbits (five for each group). Carboplatin was revealed by the 3-(4,5-dimethylthiazole-2)-yl-2,5-diphenyltetrazolium bromide test to be a potent cytostatic drug for VX2 rabbit tumor cells. We used magnetic resonance imaging to examine the tumor volume and signal intensity enhancement up to 15 min after Gd-DTPA administration within the tumor and liver before and after the different therapies. These parameters allowed us to evaluate tumor growth and vitality as well as liver injury for the different therapy types. The results found by magnetic resonance imaging corresponded very well to those obtained by histological analysis of the tumors. The chemoembolization therapies were significantly more efficient than the other therapies, as indicated by the reduction of signal intensity enhancement after contrast agent administration within the tumor and by the histologically determined necrotic fraction after therapy. In addition, we found a significant decrease of the tumor volume and no significant live injury for a therapy with Carboplat and Gelfoam.

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.

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.

Stealth liposomal 5-fluorouracil with or without degradable starch microspheres for hepatic arterial infusion in the treatment of liver metastases. An animal study in VX-2 liver tumor-bearing rabbits.

PURPOSE: Regional application of cytostatics in liver metastases leads to increased concentrations in tumor tissue. Flow retardation by temporary occlusion and drug targeting via liposome encapsulation (PEG liposomes) will further increase tumor concentrations. MATERIALS AND METHODS: Liver tumor-bearing rabbits were submitted to i.v. or i.a. therapy with or without liposome-encapsulated 5-fluorouracil (5-FU). I.a. groups were additionally treated with or without degradable starch microspheres. Tumor concentrations were calculated by HPLC as area under the curve (AUC). RESULTS: A comparison with i.v.-applied 5-FU yielded the following increasing concentrations: 5-FU-PEG liposomes i.v. 6-fold, 5-FU i.a. 20-fold, 5-FU i.a. + DSM 226-fold, 5-FU-PEG liposomes i.a. 319-fold, 5-FU-PEG liposomes i.a. + DSM 2203-fold. CONCLUSION: The intratumoral concentration of 5-FU was increased up to 2203 times the intravenous dose by combination of regional application via the hepatic artery with temporary embolization by degradable starch microspheres and drug targeting by liposome encapsulated 5-FU.

Multicenter pilot study of 5-fluorouracil, folinic acid, interferon alpha-2b and degradable starch microspheres via hepatic arterial infusion in patients with nonresectable colorectal liver metastases.

BACKGROUND: It is necessary to establish therapeutic regimens for patients with nonresectable hepatic metastases of colorectal carcinoma. A new regional chemotherapy regimen was tested in a prospective study in three centers. PATIENTS AND METHODS: An arterial port system was implanted in 95 patients. From January 1994 to March 1999, intra-arterial treatment was applied via the hepatic artery using 450 mg starch microspheres with 5 million IU recombinant interferon-alpha 2B, 500 mg/m2 folinic acid and 600 mg/m2 5-FU body surface for 5 days with a 14-day interval. RESULTS: The tumor response rate was 70%. Median disease progression was 17 months, median survival 24 months. The subgroup analysis shows a significant advantage (p<0.00001) for patients with a liver tumor involvement of <25% and a median survival of 39 months compared to a tumor involvement of 25-50% (24 months) and >50% (14 months). Major toxicity problems were observed in 11%. However, there was no termination of therapy on account of these problems. CONCLUSION: Intra-arterial chemotherapy with our new regimen was useful in patients with colorectal liver metastases who had only an intrahepatic tumor burden of <50%.

[Diagnostics and surgical therapy of enteric intussusception in adults illustrated by three cases]. / Dünndarminvagination beim Erwachsenen. Diagnostik und chirurgische Therapie anhand von 3 Fallbeispielen.

The diagnosis of enteric intussusception is rare in adults but not in children. The clinical picture often takes an insidious course. Acute abdomen may also be caused by enteric intussusception. We report on three patients with enteric intussusception and acute abdomen. In two cases, a CT led to the diagnosis of invagination of the small intestine. In one patient, invagination of the terminal ileum was detected during coloscopy. All patients were submitted to limited segment resection and end-to-end anastomosis. In all three cases, the invagination was caused by benign pathological changes. Enteric intussusception in adults always requires surgery. In more than 95% of the cases, pathological findings are obtained intraoperatively, which are benign in the small intestine in 85-95% of the cases.

[Stump closure in laparoscopic appendectomy. Influence of endoloop or linear stapler on patient outcome]. / Stumpfverschluss bei der laparoskopischen Appendektomie. Einfluss der endoskopischen Schlinge oder des Linearstaplers auf das Patientenoutcome.

BACKGROUND: Even though laparoscopic appendectomy is one of the most frequent procedures in abdominal surgery, the technique of appendiceal stump closure is still not standardized. The aim of this retrospective study was to analyze the effect of the use of endoloops or linear staplers for appendiceal stump closure concerning surgical site infections (SSI) and intra-abdominal abscesses (IAA). PATIENTS AND METHODS: All laparoscopic appendectomies between January 1st 2007 and May 31st 2010 were split into an endoloop group (ELG) and a linear stapler group (LSG). The groups were compared with respect to the outcome parameters SSI and IAA. RESULTS: A total of 430 appendectomies were performed in the study period of which 105 operations were conducted laparoscopically. In this study 47.6 % (n = 50) were alloted to the LSG and 52.4 % (n = 55) to ELG. In LSG 3.1 % (n = 1) developed an SSI versus 10.0 % (n = 4, p = 0.254) in ELG. No IAAs occurred in LSG compared to 2 (5.1 %, p = 0.499) in ELG. CONCLUSION: The use of EL for appendiceal stump closure is safe and cost effective for low-grade appendicitis but high-grade appendicitis should be treated with LS.

Hepatic arterial infusion in the treatment of liver metastases with PEG liposomes in combination with degradable starch microspheres (DSM) increases tumor 5-FU concentration. an animal study in CC-531 liver tumor-bearing rats.

UNLABELLED: The regional application of cytostatics in liver metastases leads to increased concentrations in the tumor tissue. The effect of flow retardation by temporary occlusion and drug targeting with liposome encapsulation (PEG liposomes) on tumor 5-fluorouracil (5-FU) concentrations was investigated. MATERIALS AND METHODS: Tumor-bearing rats were submitted to i.v. or intraarterial (i.a.) therapy with liposome-encapsulated or non-encapsulated 5-FU. The i.a. groups were additionally treated with or without Spherex® degradable starch microspheres (DSM). The tumor 5-FU concentrations were determined by high-performance liquid chromatography (HPLC) as area under the curve (AUC). RESULTS: A comparison with i.v. in administered 5-FU yielded the following increases tumor concentrations: 5-FU-PEG liposomes i.v. 27-fold, 5-FU i.a. 19-fold, 5-FU i.a. + DSM 1760-fold, 5-FU-PEG liposomes i.a. 110-fold, 5-FU-PEG liposomes i.a. + DSM 7665-fold. CONCLUSION: Liver intratumoral 5-FU concentration increases to >7,500 times that following i.v. administration by a combination of regional administration via the hepatic artery with temporary embolization by DSM and drug targeting by liposome-encapsulated 5-FU.

Improvement of biodistribution with PEGylated liposomes containing docetaxel with degradable starch microspheres for hepatic arterial infusion in the treatment of liver metastases: a study in CC-531 liver tumor-bearing WAG RIJ rats.

AIM: To improve the drug concentration in liver metastases, docetaxel was encapsulated in polyethyleneglycol-liposomes and administered regionally with degradable starch microspheres (DSM). MATERIALS AND METHODS: A rodent model of solitary metastasis (CC-531 adenocarcinoma) was studied. The animals were randomized into six groups and treated with 15 ng/kg docetaxel: I: intravenous (i.v.). II: PEG-liposomes i.v.; III: intraartial (i.a.) via the hepatica artery; IV: i.a.) + DSM; V: PEG-liposomes i.a.; and VI: PEG-liposomes i.a. + DSM. The docetaxel concentration in the serum, liver and liver tumor at defined times (5, 15, 30, 60,120 240 min and 24 h) was measured using HPLC. RESULTS: The area under the concentration (AUC) versus time curves showed an 11-fold higher concentration in the tumor tissue when comparing the docetaxel-PEG-liposomes i.a. + DSM group to the i.v. group (p<0.01). CONCLUSION: Compared to intravenous therapy, i.a. therapy with docetaxel-PEG-liposomes + DSM results in higher tumor tissue concentrations.

[Results of multivisceral resection of primary colorectal cancer]. / Ergebnisse der multiviszeralen Resektion des primären kolorektalen Karzinoms.

BACKGROUND: In about 10 % of all patients with colorectal cancer, the primary invention already discloses adhesions or infiltration of adjacent organs. En bloc resection of the tumor-bearing bowel segment with adjacent organs is done to give patients a chance for curation, since intraoperative differentiation is not possible. The aim of this study is characterization of the patient population as well as evaluation of the morbidity and mortality associated with this type of extensive intervention. METHOD: Between 1/95 and 6/04, we analyzed all patients with progressive primary colorectal cancer, who underwent multivisceral surgery with en bloc resection of at least one other organ. The target parameters were tumor characteristics as well as postoperative morbidity and mortality. RESULTS: A total of 1 001 patients with colorectal cancer underwent surgery. 101 patients (10 %) required multivisceral resection. In 17 % the indication was exigent. About 70 % of the interventions involved the colon. Tumor perforation was seen in 17 % of patients with colon cancer and 16 % with rectal cancer. Resection of the inner genitals was most frequent in both colon and rectal cancer (26 and 84 %) followed by small bowel resection (21 %) and partial bladder resection (19 %). Other organs play a secondary role in rectal cancer while partial bladder resection (20 %) and abdominal wall resection (14 %) is observed more frequently in colon cancer. Resection of parenchymatous organs (kidney, suprarenal gland, spleen, pancreas, liver) and others like the stomach is quite rare in colon cancer. Actual tumor infiltration (T4 situation) was observed in 51 % of patients with colon cancer and in 64 % of those with rectal cancer. Local R0 resection (97 vs. 96 %) was successfully performed in nearly all colon and rectal cancer patients. The surgical major complication rate was 9 % in colon cancer and 19 % in rectal cancer. The mortality rate was 4 %. CONCLUSION: Multivisceral en-bloc resection enables local R0 resection in the majority of cases with primary colorectal cancer. Despite sometimes extensive surgery, this type of procedure is associated with an acceptable morbidity and mortality. Since long-term survival is comparable to that in the T category (T3 or T4), multivisceral en-bloc resection is not only justified but also absolutely required in interventions with curative intention.

[Infected urachal cyst in an adult - a case report and review of literature]. / Die infizierte Urachuszyste des Erwachsenen - Eine Fallvorstellung und Literaturübersicht -

Infected urachal cysts are a rare clinical manifestation in adults. We present the case of a female patient with an infected urachal cyst, discuss the embryology, clinical presentation, diagnostics and the therapeutic procedure and make a comparison with the literature.

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.

Simultaneous determination of 5-fluorouracil and its active metabolites in serum and tissue by high-performance liquid chromatography.

In order to observe the biodistribution of 5-fluorouracil (5-FU) and its main metabolites in different kinds of tissue (tumor, liver, kidney, spleen, mucosa, lungs, heart, peritoneum, pancreas) and serum according to various novel application forms, a simple and rapid method for the simultaneous determination of 5-FU and its active metabolites 5-fluorouridine (5-FUrd) and 5-fluoro-2'-deoxyuridine (5-FdUrd) has been established. Proteins in serum and tissue samples were precipitated by perchloric acid after addition of the internal standard 5-bromouracil. The compounds were separated using an ODS Hypersil (5 microm) column and detected by UV absorbance (254 nm). Specificity, linearity, reproducibility, intermediate precision and accuracy of the method were established. The lower limit of quantitation (LOQ) for the compounds in serum and various tissue samples was determined. Data on the recovery of the compounds and the internal standard are provided.

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, NaHCO(3) 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. An experimental study on liver tumor-bearing rabbits.

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.