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1.
Med Klin Intensivmed Notfmed ; 118(2): 132-140, 2023 Mar.
Article in German | MEDLINE | ID: mdl-34928407

ABSTRACT

BACKGROUND: Patients with atraumatic abdominal pain are common in the emergency department and have a relatively high hospital mortality, with a very wide spectrum of different causes. Rapid, goal-directed diagnosis is essential in this context. METHODS: In a Delphi process with representatives of different disciplines, a diagnostic treatment pathway was designed, which is called the Abdominal Pain Unit (APU). RESULTS: The treatment pathway was designed as an extended event process chain. Crucial decision points were specified using standard operating procedures. DISCUSSION: The APU treatment pathway establishes a consistent treatment structure for patients with atraumatic abdominal pain. It has the potential to improve the quality of care and reduce intrahospital mortality over the long term.


Subject(s)
Abdominal Pain , Emergency Service, Hospital , Humans , Abdominal Pain/etiology , Abdominal Pain/therapy , Hospital Mortality
2.
Langenbecks Arch Surg ; 405(5): 551-561, 2020 Aug.
Article in English | MEDLINE | ID: mdl-32602079

ABSTRACT

BACKGROUND: Within the last years, single-incision laparoscopic cholecystectomy (SLC) emerged as an alternative to multiport laparoscopic cholecystectomy (MLC). SLC has advantages in cosmetic results, and postoperative pain seems lower. Overall complications are comparable between SLC and MLC. However, long-term results of randomized trials are lacking, notably to answer questions about incisional hernia rates, long-term cosmetic impact and chronic pain. METHODS: A randomized trial of SLC versus MLC with a total of 193 patients between December 2009 and June 2011 was performed. The primary endpoint was postoperative pain on the first day after surgery. Secondary endpoints were conversion rate, operative time, intraoperative and postoperative morbidity, technical feasibility and hospital stay. A long-term follow-up after surgery was added. RESULTS: Ninety-eight patients (50.8%) underwent SLC, and 95 patients (49.2%) had MLC. Pain on the first postoperative day showed no difference between the operative procedures (SLC vs. MLC, 3.4 ± 1.8 vs. 3.7 ± 1.9, respectively; p = 0.317). No significant differences were observed in operating time or the overall rate of postoperative complications (4.1% vs. 3.2%; p = 0.731). SLC exhibited better cosmetic results in the short term. In the long term, after a mean of 70.4 months, there were no differences in incisional hernia rate, cosmetic results or pain at the incision between the two groups. CONCLUSIONS: Taking into account a follow-up rate of 68%, the early postoperative advantages of SLC in relation to cosmetic appearance and pain did not persist in the long term. In the present trial, there was no difference in incisional hernia rates between SLC and MLC, but the sample size is too small for a final conclusion regarding hernia rates. TRIAL REGISTRATION: German Registry of Clinical Trials DRKS00012447.


Subject(s)
Cholecystectomy, Laparoscopic/methods , Pain, Postoperative/epidemiology , Adult , Aged , Aged, 80 and over , Conversion to Open Surgery/statistics & numerical data , Esthetics , Female , Follow-Up Studies , Germany/epidemiology , Humans , Incisional Hernia/epidemiology , Length of Stay/statistics & numerical data , Male , Middle Aged , Operative Time , Pain Measurement , Prospective Studies
3.
Surg Endosc ; 34(1): 126-132, 2020 01.
Article in English | MEDLINE | ID: mdl-30863926

ABSTRACT

BACKGROUND: Single-incision laparoscopic surgery (SILS) is growing in popularity. The increased diameter of the umbilical incision might raise questions about the possibility of a greater risk of postoperative incisional hernia in comparison to conventional laparoscopy. This study aims to disclose the frequency of incisional hernia after SILS in long-term follow-up as well as to reveal the factors predisposing patients to this feared complication. METHODS: The patient collective consists of cholecystectomy and appendectomy patients, who were operated on using SILS technique. Follow-up was achieved through letter correspondence, telephone interview, and clinical examination. Effects of demographic variables and operative parameters including age, sex, BMI, ASA score, duration of surgery, pre-existing hernia as well as postoperative incidence of incisional hernia were investigated using univariate and multivariate analyses. RESULTS: A total of 286 cases with complete follow-up were included in the analyses. Mean follow-up duration was 58.4 months. 192 patients (67.1%) underwent cholecystectomy; 94 (32.9%) had an appendectomy. The study collective consisted of 218 women (76.2%) and 68 men (23.8%). Mean age at the date of the operation was 38.5 (median 36, range 13-74). In 5 cases (1.7%), the surgical approach was converted into conventional laparoscopy. Intraoperative complication rate was 0.3% and postoperative complication rate was 5.9%. 7 patients (2.4%) developed an incisional hernia. Obese patients had an incisional hernia incidence of 10.9%. 3 out of 19 patients (15.8%) with a pre-existing umbilical hernia developed an incisional hernia during follow-up. Obesity and pre-existing umbilical hernia proved to have a significant association with incisional hernia incidence in univariate and multivariate analyses. Sex, age, procedure (appendectomy vs cholecystectomy), presence of acute inflammation, and duration of surgery did not show a statistically significant association with incisional hernia. CONCLUSION: Detection of incisional hernia necessitates a long follow-up duration. Obesity and pre-existing umbilical hernia are associated with a higher incidence of this complication. Following a careful patient selection, SILS offers a safe approach for cholecystectomy and appendectomy procedures.


Subject(s)
Appendectomy , Cholecystectomy , Incisional Hernia , Postoperative Complications , Adult , Appendectomy/adverse effects , Appendectomy/methods , Cholecystectomy/adverse effects , Cholecystectomy/methods , Female , Follow-Up Studies , Germany/epidemiology , Humans , Incidence , Incisional Hernia/epidemiology , Incisional Hernia/etiology , Long Term Adverse Effects/epidemiology , Long Term Adverse Effects/etiology , Male , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Risk Adjustment/methods , Risk Factors
4.
Handchir Mikrochir Plast Chir ; 52(4): 289-296, 2020 Aug.
Article in German | MEDLINE | ID: mdl-31610580

ABSTRACT

The radial forearm flap has become a standard for phalloplasty in gender confirmation surgery (gcS) from female to male (FtM). However, there is a lack of experience regarding the use of a prelaminated urethra compared with the older techniques reported by Chang and Gottlieb and Levine. This paper assesses the complications of the individual surgical steps pursuant to the Clavien-Dindo classification. PATIENTS AND METHODS: All patients undergoing gender reassignment surgery in our department between 1 January 2011 and 30 June 2017 using a radial forearm phalloplasty with a prelaminated urethra for gcS were included in this study. The total number of patients was 39. The complications after colpectomy, urethral prelamination, phalloplasty, implantation of testicular implants and glans-plasty were assessed. The follow-up after phalloplasty ranged between 6 and 80 months and was 32 months on average. Complications were classified according to Clavien Dindo. RESULTS: Phalloplasty was uneventful in 5 out of 39 patients (12.8 %). In 22 patients (56.4 %) a grade I complication occurred. Four patients (10.3 %) sustained a grade II complication, 16 (41 %) had a grade IIIb complication and one patient had a grade IV complication (2.6 %). Twenty-eight out of 39 patients (71.8 %) developed urethral fistulas in the direct postoperative course. However, only 8 of these patients (20.5 % of the total population) required surgical revision due to fistulas. Five patients developed a urethral stenosis (12.8 %) requiring surgical revision; in two of them this happened several times (8 stenoses in total). Flap losses occurred in two patients (5.1 %). CONCLUSION: Radial forearm phalloplasty with a prelaminated urethra has become a well-established procedure in female-to-male gender reassignment surgery. In our study, the rate of urological complications was significantly reduced to a level lower than those reported in previous studies. The number of fistulas was significantly reduced during our learning curve and by surgical modifications such as a visor flap at the site of the urethral anastomosis. This large series provides a database of complications classified according to Clavien Dindo for comparison with future techniques and innovations.


Subject(s)
Sex Reassignment Surgery , Transsexualism/surgery , Female , Forearm , Humans , Male , Postoperative Complications/etiology , Surgical Flaps , Urethra/surgery
5.
Zentralbl Chir ; 142(1): 113-121, 2017 Feb.
Article in German | MEDLINE | ID: mdl-28303560

ABSTRACT

Background An enterothorax with herniation of bowel segments through a diaphragmatic defect is a rare postoperative complication, which can occur in the early postoperative period as well as several months or even years after the primary procedure. In virtually all cases, this diagnosis requires surgical treatment with reposition of the herniated structures and closure of the diaphragmatic defect. The aim of this study was to describe a larger case series of a rare complication and to present a review of the literature. Material and Methods The data of all patients treated for postoperative enterothorax at our centre were retrospectively analysed with a special focus on time of occurrence, type of clinical symptoms, surgical treatment and postoperative morbidity. Results From March 2007 to October 2014, twenty patients underwent surgery due to postoperative enterothorax. Six cases (30 %) were early postoperative complications (mean 10th postoperative day); in 14 patients (70 %) the enterothorax presented with delay (mean 42 months after primary surgery). The variance of the clinical symptoms was wide, but in the majority of cases, patients presented with symptoms of ileus or new-onset dyspnoea. In two patients (10 %) the diagnosis was an incidental finding without clinical symptoms. Computed tomography (CT) was performed in 70 % (n = 14), chest X-rays in 30 % (n = 6) of patients for diagnosis. Immediate laparotomy was performed in 15 % (n = 3) of cases. The diaphragmatic defect involved the left side in 75 % of cases (n = 15). Surgical treatment was performed via laparotomy in all patients. The diaphragm was closed by a direct suture in 70 % of patients (n = 14); in six patients (30 %) an augmentation (mesh or tissue patch) was added. Overall postoperative morbidity was 55 %; for elective operations it was 0 %. One patient died in the further postoperative course. Conclusion Postoperative enterothorax may occur early or years after primary surgery. Surgical treatment should be performed in a timely manner even in asymptomatic patients to avoid further complications.


Subject(s)
Hernia, Diaphragmatic/surgery , Incisional Hernia/surgery , Adult , Aged , Dyspnea/etiology , Female , Follow-Up Studies , Hernia, Diaphragmatic/diagnosis , Humans , Ileus/etiology , Incisional Hernia/diagnosis , Male , Middle Aged , Reoperation , Retrospective Studies , Surgical Mesh , Suture Techniques , Tomography, X-Ray Computed
6.
Dig Endosc ; 29(3): 377-382, 2017 May.
Article in English | MEDLINE | ID: mdl-28112447

ABSTRACT

Minimally invasive or endoscopic transluminal drainage and necrosectomy are the standard of care for infected pancreatic fluid collections and necroses after pancreatitis. In an endoscopic treatment algorithm, necroses beyond the reach of safe endoscopic access are typically treated by percutaneous drainage. We aimed to evaluate percutaneous minimally invasive necrosectomy using a purely endoscopic technique in patients with extensive necrosis. In patients with necroses beyond safe transluminal reach, the percutaneous drainage canal was used for flexible endoscopic access and dilatation of the tract to 20 mm. Percutaneous endoscopic necrosectomy was carried out through this canal. We present a case series of 14 patients in whom between one and four necrosectomy (median two) sessions were done to remove solid necroses successfully in 13 out of 14 patients. There were no major complications apart from one patient with abdominal compartment syndrome secondary to delayed erosion of the splenic artery. Percutaneous flexible necrosectomy might evolve into an alternative to surgical minimally invasive necrosectomy in anatomical sites beyond transluminal endoscopic reach.


Subject(s)
Endoscopes , Endosonography , Minimally Invasive Surgical Procedures/methods , Pancreas/diagnostic imaging , Pancreatectomy/methods , Pancreatitis, Acute Necrotizing/surgery , Surgery, Computer-Assisted/methods , Aged , Female , Humans , Male , Middle Aged , Pancreas/surgery , Pancreatitis, Acute Necrotizing/diagnostic imaging , Retroperitoneal Space , Treatment Outcome
7.
Langenbecks Arch Surg ; 396(5): 709-15, 2011 Jun.
Article in English | MEDLINE | ID: mdl-21384187

ABSTRACT

PURPOSE: In the recent past, access to the peritoneal cavity has involved primarily 'natural orifice transluminal' and 'single-port access' techniques, which are based on laparoscopy. The most frequently performed procedure using these new developments is cholecystectomy. Few studies compare more than one 'new' method with the 'golden standard' of laparoscopic cholecystectomy. Here we present the results of the first prospective observational study comparing standard laparoscopic cholecystectomy with single-port cholecystectomy as well as transvaginal-hybrid cholecystectomy. METHODS: Fifty-one patients were included in a prospective observational study (20 four-trocar laparoscopic, 15 transvaginal-hybrid, 16 single-port cholecystectomies). Endpoints of the study were operative time, length of hospital stay and postoperative level of pain (numeric analogue score, while coughing). Conversion rates and complications are reported as well. RESULTS: Median operating times did not differ among all three access methods [55 (35-135) min vs. 65 (35-95) min vs. 68 (35-98) min]. Hospital stay was significantly shorter in the transvaginal-hybrid group [3 (3-12) days] and in the single-port group [3 (1-9) days], compared to the four-trocar laparoscopic group [4 (2-17) days]. Pain score was significantly diminished in the transvaginal-hybrid group during the early postoperative course. CONCLUSIONS: Concerning the length of hospital stay, transvaginal-hybrid cholecystectomy and single-port cholecystectomy appear to be superior to 'conventional' laparoscopic cholecystectomy. Additionally, transvaginal-hybrid access is associated with significantly less pain in the early postoperative course.


Subject(s)
Cholecystectomy, Laparoscopic/methods , Cholecystectomy/methods , Cholecystitis/surgery , Cholelithiasis/surgery , Natural Orifice Endoscopic Surgery/methods , Vagina/surgery , Adult , Aged , Aged, 80 and over , Female , Humans , Length of Stay , Male , Middle Aged , Pain Measurement , Pain, Postoperative/etiology , Postoperative Complications/etiology , Prospective Studies , Time and Motion Studies
8.
Inflammation ; 34(6): 597-602, 2011 Dec.
Article in English | MEDLINE | ID: mdl-20963474

ABSTRACT

Different dietary fatty acids affect eicosanoid metabolism in different ways, thus influencing the pro- and anti-inflammatory balance of prostaglandins and leukotrienes. Therefore, we analyzed the impact of [n-3], [n-6], and [n-9] fatty acids on eicosanoid metabolism and histopathology in acute pancreatitis in rats. Seventy-five male Sprague-Dawley rats were randomized into five groups (n = 15). Group 1 underwent only laparotomy, while in groups, 2-5 pancreatitis was induced. Groups 1 and 2 were then given saline infusion, groups 3-5 received fat emulsion (group 3: rich in [n-6], group 4: rich in [n-9], group 5: rich in [n-3] fatty acids) for another 18 h. Infusion rich in [n-3] fatty acids significantly decreased histopathological severity of pancreatitis, compared to all other groups. There was no difference concerning the concentrations of prostaglandins and leukotrienes between all groups. Parenteral infusion rich in [n-3] fatty acids reduced histopathological severity of acute pancreatitis in rats without changing eicosanoid metabolism at the endpoint.


Subject(s)
Dietary Fats, Unsaturated/pharmacology , Eicosanoids/biosynthesis , Fish Oils/pharmacology , Pancreatitis/drug therapy , Animals , Dietary Fats, Unsaturated/therapeutic use , Fish Oils/administration & dosage , Fish Oils/therapeutic use , Olive Oil , Plant Oils/pharmacology , Rats , Rats, Sprague-Dawley , Glycine max
9.
Int J Colorectal Dis ; 25(2): 245-50, 2010 Feb.
Article in English | MEDLINE | ID: mdl-19902227

ABSTRACT

PURPOSE: Surgical cytoreduction of peritoneal surface malignancy of colorectal origin in combination with hyperthermic intraoperative peritoneal chemotherapy (HIPEC) has become an established treatment approach. Only a few of animal models for scientific research on various therapeutic strategies have been described yet. The feasibility of an established rat model with a peritoneal surface malignancy from colorectal origin for treatment investigation should be examined in this study. METHODS: Peritoneal surface malignancy of colonic origin was induced in 90 male BD IX rats. Animals were randomised into six groups (15 animals per one control and five treatment groups). One treatment group underwent only surgical debulking. The animals of the other four treatment groups received additional interventions: hyperthermic intraperitoneal chemotherapy with mitomycin or gemcitabine, photodynamic therapy or taurolidine lavage. Twenty-one days after treatment, the intraperitoneal status was investigated. Tumour weight, count of tumour nodules and experimental Peritoneal Carcinosis Index (ePCI) were detected. RESULTS: Extended surgical cytoreduction and additional treatments including HIPEC were feasible in this rat model. All treatment groups had a significant lower tumour weight, account of tumour nodes and ePCI if compared with the control group. Comparing the additional therapies only HIPEC with mitomycin lead to relevant tumour reduction after surgery. CONCLUSION: This rat model is suitable for research on the multimodal treatment of peritoneal malignancies. A persisting cytoreductive effect of surgical tumour debulking could be proven. Only additional HIPEC therapy with mitomycin showed a significant tumour reduction. This animal model provides the opportunity to investigate different therapeutic strategies.


Subject(s)
Antimetabolites, Antineoplastic/administration & dosage , Colonic Neoplasms/pathology , Deoxycytidine/analogs & derivatives , Hypothermia, Induced , Mitomycin/administration & dosage , Peritoneal Neoplasms/therapy , Photochemotherapy , Taurine/analogs & derivatives , Thiadiazines/administration & dosage , Animals , Cell Line, Tumor , Chemotherapy, Adjuvant , Deoxycytidine/administration & dosage , Disease Models, Animal , Infusions, Parenteral , Male , Neoplasm Transplantation , Peritoneal Neoplasms/drug therapy , Peritoneal Neoplasms/secondary , Peritoneal Neoplasms/surgery , Rats , Taurine/administration & dosage , Therapeutic Irrigation , Time Factors , Tumor Burden , Gemcitabine
10.
Pancreas ; 38(4): 436-41, 2009 May.
Article in English | MEDLINE | ID: mdl-19295455

ABSTRACT

OBJECTIVE: Previously, we observed decreased histopathological severity of acute necrotizing pancreatitis (ANP) by parenteral nutrition with n-3 fatty acids. Thus, we now sequentially analyzed the impact of n-3 fatty acids on prostaglandin and leukotriene synthesis in ANP. METHODS: One hundred ninety-eight Sprague-Dawley rats (11 groups, n = 18) underwent intraductal glycodesoxycholat instillation and 6-hour cerulein infusion. Afterward, saline was infused in groups 2, 4, 6, 8, and 10, whereas groups 3, 5, 7, 9, and 11 received infusion rich in n-3 fatty acids (Omegaven, Fresenius Kabi, Bad Homburg, Germany). Animals were killed after 6 (group 1), 10 (groups 2 and 3), 14 (groups 4 and 5), 18 (groups 6 and 7), 22 (groups 8 and 9), and 26 hours (groups 10 and 11). The pancreas was histopathologically examined, and the pancreatic eicosanoid metabolism (prostaglandin E2, prostaglandin F1alpha [PGF1alpha], and leukotrienes) and lipid peroxidation (thiobarbituric acid-reactive substance, superoxide dismutase, and glutathione peroxidase) were analyzed. RESULTS: Between the 14th and 26th hours, histopathologic scores (edema, inflammation, bleeding, and necrosis) were reduced in the n-3 fatty acid group compared with the corresponding saline group. Pancreatic prostaglandin E2 and PGF1alpha were decreased between the 10th and 18th hour by n-3 fatty acids; PGF1alpha was reduced after 26 hours compared with the corresponding saline group. Lipid peroxidation was decreased by n-3 fatty acids after 14 hours (thiobarbituric acid-reactive substance); however, there was no difference concerning lipid peroxidation protective enzymes (glutathione peroxidase and superoxide dismutase). CONCLUSIONS: Parenteral therapy with n-3 fatty acids decreased histopathologic severity in ANP by early inhibition of prostaglandin (E2 and F1alpha) synthesis and reduction of lipid peroxidation.


Subject(s)
Fatty Acids, Omega-3/pharmacology , Pancreas/drug effects , Pancreatitis, Acute Necrotizing/prevention & control , Prostaglandins/biosynthesis , Animals , Ceruletide , Dinoprostone/metabolism , Fatty Acids, Omega-3/administration & dosage , Fatty Acids, Omega-3/therapeutic use , Glutathione Peroxidase/metabolism , Leukotrienes/metabolism , Lipid Peroxidation/drug effects , Male , Pancreas/metabolism , Pancreas/pathology , Pancreatitis, Acute Necrotizing/chemically induced , Pancreatitis, Acute Necrotizing/metabolism , Prostaglandins F/metabolism , Rats , Rats, Sprague-Dawley , Superoxide Dismutase/metabolism , Thiobarbituric Acid Reactive Substances/metabolism , Time Factors
11.
Clin Exp Metastasis ; 25(4): 445-9, 2008.
Article in English | MEDLINE | ID: mdl-18301991

ABSTRACT

Surgical therapy of peritoneal surface malignancy from colorectal origin in combination with Hyperthermic Intraoperative Peritoneal Chemotherapy (HIPEC) has now become an established treatment approach in very few specialised centres. A peritonectomy procedure is possible to perform with additional HIPEC in patients. An experimental model to simulate peritonectomy procedure and HIPEC does not exist so far in rats. Nevertheless, animal models seem to be very important for evaluation of new therapeutic opportunities and toxicity of different multimodal therapies. In a first step we analysed the surgical tumour debulking of peritoneal surface malignancy in rats. A peritoneal surface malignancy from colonic origin was induced in 75 male BD IX rats. Twenty one days after induction of peritoneal surface malignancy rats were randomised and animals intend to create an operation with surgical tumour debulking. There was no tumour growth in two animals. The aim of the peritonectomy procedure was the complete tumour reduction. In this study the results of the surgical approach will be described. A complete tumour reduction (R0) was achieved in 34 animals. In 39 rats a macroscopic tumour deposit was left behind (R2). The intraoperative experimental Peritoneal Cancer Index (ePCI) was used to describe tumour weight and number of tumour inoculations. Both parameters were found to be dependent factors of complete tumour reduction. Six animals died due to therapeutical interventions. Surgical tumour debulking in rats with peritoneal surface malignancy is possible with high reliability and a low mortality rate. This animal model could be an important step for investigation of multimodal treatment options and toxicity in treatment regimens of peritoneal surface malignancy.


Subject(s)
Peritoneal Neoplasms/surgery , Peritoneum/surgery , Animals , Disease Models, Animal , Male , Rats
12.
J Gastroenterol Hepatol ; 22(11): 1872-6, 2007 Nov.
Article in English | MEDLINE | ID: mdl-17914962

ABSTRACT

BACKGROUND AND AIM: Octreotide is considered to reduce exocrine pancreatic secretion in acute hemorrhagic necrotizing pancreatitis decreasing pancreatic autodigestion. The aim of this study was to determine whether octreotide also has antioxidative effects in acute pancreatitis. Additionally time and dose of application were of interest. METHOD: Ninety male Sprague-Dawley rats were randomized into six groups (n = 15). Group 1 underwent a laparotomy, and animals in groups 2-6 received intraductal glycodeoxycholic acid followed by intravenous cerulein. Groups 3 and 4 were injected with 0.5 mg octreotide, while groups 5 and 6 received continuous intravenous infusion of 0.05 mg octreotide/h for 10 h. Treatment was initiated 6 hours after induction of pancreatitis (IP) in groups 3 and 5, and 14 h after IP in groups 4 and 6. At 24 h after IP all animals were killed and each pancreas was analyzed histopathologically. In addition, levels of pancreatic lipid peroxidation protective enzymes glutathione-peroxidase (GSH-Px) and superoxide dismutase (SOD) as well as lipid peroxidation via thiobarbituric acid reactive substances (TBARS) were determined. RESULTS: Early bolus application of octreotide reduced severity of histopathological changes in acute pancreatitis and decreased lipid peroxidation in pancreatic tissue samples; however, late bolus application and continuous intravenous infusion did not influence pancreatitis or lipid peroxidation. CONCLUSION: Octreotide seems to have a dose- and time-dependent effect on histopathology and lipid peroxidation in a model of pancreatitis in rats.


Subject(s)
Antioxidants/pharmacology , Hemorrhage/prevention & control , Octreotide/pharmacology , Pancreas/drug effects , Pancreatitis, Acute Necrotizing/prevention & control , Animals , Antioxidants/administration & dosage , Ceruletide , Disease Models, Animal , Dose-Response Relationship, Drug , Glutathione Peroxidase/metabolism , Glycodeoxycholic Acid , Hemorrhage/etiology , Hemorrhage/metabolism , Hemorrhage/pathology , Infusions, Intravenous , Injections, Intravenous , Lipid Peroxidation/drug effects , Male , Octreotide/administration & dosage , Pancreas/enzymology , Pancreas/metabolism , Pancreas/pathology , Pancreatitis, Acute Necrotizing/chemically induced , Pancreatitis, Acute Necrotizing/complications , Pancreatitis, Acute Necrotizing/metabolism , Pancreatitis, Acute Necrotizing/pathology , Rats , Rats, Sprague-Dawley , Superoxide Dismutase/metabolism , Thiobarbituric Acid Reactive Substances/metabolism , Time Factors
13.
Clin Exp Metastasis ; 22(1): 77-83, 2005.
Article in English | MEDLINE | ID: mdl-16132581

ABSTRACT

BACKGROUND: Experimental studies have shown that taurolidine suppresses intraperitoneal tumor growth following local application in rats. In opposite, a single intravenous therapy affected neither intraperitoneal nor subcutaneous growth of malignancies. Thus, an intravenous long-term therapy with taurolidine was investigated in rats after administration of a subcutaneous tumor load. VEGF and TNFalpha production and their effects on tumor growth have not been elucidated so far. METHODS: VEGF and TNFalpha levels of rat colon adenocarcinoma cells (DHD/K12/TRb) were analyzed in the supernatant undergoing treatment of increasing taurolidine doses in vitro. Besides the cell experiments rats were treated intravenously. At the beginning of the operation, 10 000 colon adenocarcinoma cells were applied subcutaneously at the back of the rats. Then the animals (n = 80, BD IX rats) were randomized into eight groups and underwent a standardized midline laparotomy for 30 min. At the end of the operation the animals were given either a bolus (1 ml Ringer's solution) or a long-term intravenous therapy (7 days, eight-hourly 1 ml 1%, 2%, or 3% taurolidine) were performed. For long-term therapy, a jugularis vein port catheter system was placed and left for 1 week. The influence on subcutaneous tumor growth, animal growth, general side effects and leukocyte/granulocyte levels were analyzed. Total tumor weights were determined 4 weeks after cell application. RESULTS: The VEGF and TNFalpha levels decreased rapidly after taurolidine therapy with low doses in vitro. The subcutaneous tumor growth showed a downtrend of tumor weight (P = 0.075) with a statistical significance in solid tumor counts (P = 0.04) at the back of the animals. A slight and temporary depression in animal growth was observed only in long-term therapy groups. Independent of the therapeutic agents and the application forms, the operation itself caused a slight leukopenia shortly after the operation compensated by a moderate leukocytosis in the following course. Fast injections of taurolidine led to a reduction of breathing rate. CONCLUSIONS: Only the intravenous long-term therapy of 3% taurolidine led to a slight downregulation in subcutaneous tumor growth. The changes of leukocyte counts were not affected by taurolidine. Fast injections have to be avoided. The findings prompted us to start new experiments to determine the influence of increasing doses of taurolidine on progressive tumor growth in rats.


Subject(s)
Adenocarcinoma/drug therapy , Adenocarcinoma/pathology , Antineoplastic Agents/administration & dosage , Colonic Neoplasms/drug therapy , Colonic Neoplasms/pathology , Taurine/analogs & derivatives , Thiadiazines/administration & dosage , Animals , Antineoplastic Agents/therapeutic use , Body Weight/drug effects , Cell Line, Tumor , Injections, Intravenous , Leukocyte Count , Neoplasm Metastasis , Neoplasm Transplantation , Rats , Taurine/administration & dosage , Taurine/therapeutic use , Thiadiazines/therapeutic use , Tumor Necrosis Factor-alpha/metabolism , Vascular Endothelial Growth Factor A/metabolism
14.
Invest New Drugs ; 23(2): 157-64, 2005 Mar.
Article in English | MEDLINE | ID: mdl-15744592

ABSTRACT

BACKGROUND: There is controversial discussion whether metastasis initiated by laparoscopy with carbon dioxide might be prevented by instillation of taurolidin or radical scavengers like the somatostatin analogue Octreotide. Therefore we evaluated the effects of laparoscopic lavage with taurolidin and Octreotide on liver metastasis after staging laparoscopy in ductal pancreatic cancer. METHODS: In 60 Syrian hamsters pancreatic adenocarcinoma was induced by weekly subcutanous injection of 10 mg N-nitrosobis-2-oxopropylamin/kg body weight for 10 weeks. In the 16th week laparoscopic staging biopsy by use of carbon dioxide was performed. Finally animals underwent abdominal irrigation with saline (gr.1, n = 20), taurolidin (0.5%) (gr.2, n = 20) or Octreotide (gr.3, n = 20). In week 25 animals were sacrificed, pancreas and liver were analysed. RESULTS: Size of pancreatic carcinomas was decreased in the taurolidin gr. compared to the other two groups. Furthermore the number of liver metastasis per animal was reduced after lavage with taurolidin (2 +/- 2) and Octreotide (2.5 +/- 2) compared to saline irrigation (4 +/- 4) (p < 0.05). Additionally the incidence of port site metastases was significantly reduced in the taurolidin group. Activity of antioxidative enzyme superoxide dismutase (SOD) was increased while concentration of products of lipidperoxidation was decreased in non-metastatic liver after taurolidin irrigation compared to saline or Octreotide irrigation. CONCLUSIONS: Taurolidin irrigation during laparoscopy might be a new concept to reduce the number of liver metastasis and port site metastases in pancreatic cancer.


Subject(s)
Adenocarcinoma/drug therapy , Antineoplastic Agents/therapeutic use , Carcinoma, Pancreatic Ductal/drug therapy , Laparoscopy/adverse effects , Lipid Peroxidation/drug effects , Liver Neoplasms/prevention & control , Octreotide/therapeutic use , Pancreatic Neoplasms/drug therapy , Taurine/analogs & derivatives , Taurine/therapeutic use , Thiadiazines/therapeutic use , Adenocarcinoma/chemically induced , Adenocarcinoma/pathology , Animals , Carcinoma, Pancreatic Ductal/chemically induced , Carcinoma, Pancreatic Ductal/pathology , Cricetinae , Liver Neoplasms/pathology , Liver Neoplasms/secondary , Male , Mesocricetus , Neoplasm Metastasis/prevention & control , Pancreatic Neoplasms/chemically induced , Pancreatic Neoplasms/pathology
15.
Clin Exp Metastasis ; 20(5): 387-94, 2003.
Article in English | MEDLINE | ID: mdl-14524527

ABSTRACT

Experimental studies in the therapy of malignant abdominal tumors have shown that different cytotoxic agents suppress the intraperitoneal tumor growth. Nevertheless, a general accepted approach to prevent tumor recurrences does not exist. Following subcutaneous and intraperitoneal injection of 10(4) colon adenocarcinoma cells (DHD/K12/TRb), the influences of both taurolidine or taurolidine/heparin on intraperitoneal and subcutaneous tumor growth was investigated in 105 rats undergoing midline laparotomy. The animals were randomized into 7 groups and operated on during 30 min. To investigate the intraperitoneal (local) influence of either taurolidine or heparin on tumor growth, the substances were applied intraperitoneally. Systemic and intraperitoneal effects were evaluated after intravenous injection of the substances. Both application forms were also combined to analyze synergistic effects. Tumor weights, as well as the incidence of abdominal wound metastases, were determined four weeks after the intervention. In order to evaluate the effects of the agents, blood was taken to determine the peripheral leukocytes counts. Intraperitoneal tumor growth in rats receiving intraperitoneal application of taurolidine (median 7.0 mg, P = 0.05) and of taurolidine/heparin (median 0 mg, P = 0.02) was significantly reduced when compared to the control group (median 185 mg). The simultaneous instillation of both agents also reduced the intraperitoneal tumor growth (median 4 mg, P = 0.04), while the intravenous injection of the substances caused no local effect. In contrast, the subcutaneous tumor growth did not differ among all groups. In all groups, abdominal wound recurrences were rare and did not differ. Independent of the agents and the application form, the operation itself caused a slight leukopenia shortly after the operation and a leukocytosis in the following course. Intraperitoneal therapy of either taurolidine or in combination with heparin inhibits local tumor growth and abdominal wound recurrences in rats undergoing midline laparotomy. Neither the intraperitoneal nor the intravenous application or the combination of the two agents influenced the subcutaneous tumor growth. The substances did not alter the changes of peripheral leukocytes.


Subject(s)
Antineoplastic Agents/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Colonic Neoplasms/drug therapy , Fibrinolytic Agents/administration & dosage , Heparin/administration & dosage , Taurine/analogs & derivatives , Taurine/administration & dosage , Thiadiazines/administration & dosage , Animals , Body Weight , Cell Division , Dose-Response Relationship, Drug , Humans , Leukocytes/metabolism , Leukocytosis , Leukopenia , Male , Neoplasm Metastasis , Neoplasm Transplantation , Neoplasms, Experimental/drug therapy , Random Allocation , Rats , Temperature , Time Factors , Tumor Cells, Cultured
16.
Pancreatology ; 2(3): 211-6, 2002.
Article in English | MEDLINE | ID: mdl-12138726

ABSTRACT

BACKGROUND: The therapeutic effects of octreotide in acute hemorrhagic necrotizing pancreatitis (ANP) have always been considered to be due to the inhibition of the exocrine pancreatic secretion in order to reduce pancreatic autodigestion. In this experimental study we analyzed whether octreotide has also antioxidative effects on acute pancreatitis. METHODS: 40 male Wistar rats were randomized into four groups (n = 10). Group 1 underwent a laparotomy. Groups 2-4 received an injection of natrium taurocholate into the pancreatic duct to induce acute pancreatitis. One hour later group 2 was injected 1 ml NaCl solution intraperitoneally, while groups 3 and 4 received 0.1 or 0.2 mg octreotide, respectively. The severity of ANP was examined histologically. The lipid peroxide level as well as the activity of glutathione peroxidase and superoxide dismutase were measured in plasma and pancreatic tissue samples. RESULTS: High-dose octreotide decreased the lipid peroxide level in plasma (2.1 +/- 0.53 vs. 4.69 +/- 1.35 nmol/l; p < 0.05) and pancreatic tissue samples 4.67 +/- 1.37 vs. 13.20 +/- 2.93 nmol/ml; p < 0.05) compared to the pancreatitis control group. Low-dose octreotide, however, did not reduce lipid peroxidation. CONCLUSION: Octreotide seems to have a dose-dependent antioxidative effect in natrium taurocholate-induced pancreatitis in rats.


Subject(s)
Antioxidants/pharmacology , Lipid Peroxidation/drug effects , Lipid Peroxides/blood , Octreotide/pharmacology , Pancreas/metabolism , Pancreatitis, Acute Necrotizing/metabolism , Animals , Antioxidants/administration & dosage , Dose-Response Relationship, Drug , Glutathione Peroxidase/blood , Glutathione Peroxidase/metabolism , Male , Octreotide/administration & dosage , Osmolar Concentration , Pancreatitis, Acute Necrotizing/chemically induced , Rats , Rats, Wistar , Superoxide Dismutase/blood , Superoxide Dismutase/metabolism , Taurocholic Acid , Thiobarbituric Acid Reactive Substances/metabolism
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