The inhibition of tumor cell adhesion on human mesothelial cells (HOMC) by phospholipids in vitro.

BACKGROUND AND AIMS: Intraperitoneal tumor cell adhesion to extracellular matrix and to mesothelial cells mediated by integrins is an important step in developing peritoneal carcinosis. In former animal studies, we could demonstrate that intraperitoneal treatment with a new phospholipid (PL) emulsion significantly reduces the amount of peritoneal carcinosis by adhesion prevention. This in vitro study tries to elucidate the influence of phospholipids on cells of the human gastric cancer cell line (NUGC-4) and the human rectal cancer cell line (HRT-18) adhering to mesothelial cells (HOMC) in a monolayer culture in vitro. MATERIALS AND METHODS: HOMC cells were derived from omentum majus from patients undergoing elective abdominal surgery. Three passages of both cancer cell lines (NUGC-4 and HRT-18) were used. 1x10(5)/100 microl (HRT-18) or 1.2x10(5)/100 microl (NUGC-4) cells, according to forgoing dilution series, were pretreated with different concentrations of phospholipid emulsion (0.05, 0.1, 0.5, 0.75, 1% PL) stained with cell tracker chloromethyl-benzamidodialkylcarbocyanine (CM-DIL) and seeded into each well on the mesothelial monolayer. After 90 min, the number of adherent cells was counted by fluorescence microscopy at 530 and 620 nm. Additionally, flow cytometric analysis of integrin alpha3 and beta1 expression on the tumor cell surface after treatment with phospholipids was completed. RESULTS: We found a dose dependent effect of phospholipids on both tumor cell lines causing a reduction of cell-cell adhesion. Already low concentrations of phospholipids (PL 0.5) had a significant influence. The mean cell count could be reduced from 234+/-12/mm2 in controls to 124+/-41/mm2 (PL 0.5; NUG-4) and from 295+/-49/mm2 to 169+/-29/mm2 (PL 0.5; HRT-18), respectively. Additionally, the integrin alpha3 and beta1 expression on both cell lines could be reduced. CONCLUSION: Our results within the scope of published data indicate that adhesion prevention is capable to reduce peritoneal carcinosis.

Experimental evaluation of phospholipids and icodextrin in re-formation of peritoneal adhesions.

BACKGROUND: The formation of further adhesions after adhesiolysis is a major problem. Not all agents that are supposed to reduce de novo adhesions can reduce further adhesion formation. The efficacy and safety of intraperitoneally applied phospholipids has been shown previously. This study evaluated the influence of phospholipids and icodextrin on adhesion re-formation. METHODS: In an experimental study on 60 Chinchilla rabbits adhesions were induced by standardized abrasion of defined areas of the ventral abdominal wall, the caecum and the ileum. Open adhesiolysis was performed 10 days later. The animals randomly received either 1.5 per cent phospholipids, 4 per cent icodextrin or Ringer's lactate intraperitoneally. Half of the animals in each group were killed after a further 10 days and the remainder at 20 days. Adhesion formation was assessed by computer-aided planimetry and histopathological examination. RESULTS: Phospholipids (10 days: P = 0.001; 20 days: P = 0.012) and icodextrin (10 days: P = 0.006; 20 days: P = 0.055) reduced adhesion re-formation after both intervals compared with Ringer's lactate controls. CONCLUSION: Phospholipids and icodextrin were effective in preventing re-formation of adhesions.

Effects of intra-abdominal drainages on adhesion formation and prevention by phospholipids in a rat model. Drainages and adhesion formation.

BACKGROUND AND AIMS: The study was designed to asses the adhesiogenic capacity of silicone drainages and the protective effect of phospholipids (PL). MATERIALS AND METHODS: A total of 75 Wistar rats were randomly assigned to the different groups. In a preliminary trial (pt; n = 15), all rats underwent midline laparotomy. The control group (C(pt); n = 5) received no further treatment. In the other animals, either an 'easy flow' drainage (EF(pt); n = 5) or an 'Aachen' drainage (AC(pt); n = 5) was placed into the abdominal cavity. In the final study (fs; n = 60), rats underwent laparotomy and colonic anastomosis. The control groups (C(fs)) received no drainages. In the other groups either one of the two types of drainages (EF(fs), AC(fs)) were introduced. In 50% of the rats, 75 mg/kg of PL were administered intraperitoneally (C(fs)+PL, EF(fs)+PL, AC(fs)+PL). The other rats received no additional treatment (C(fs)ØPL, EF(fs)ØPL, AC(fs)ØPL). All animals were sacrificed 10 days after surgery. Areas of adhesions and anastomotic bursting pressures were measured (mean +/- SD). RESULTS: In the preliminary trial, analysis of variance (ANOVA) revealed no differences between the groups after application of drainages (values are given in mean +/- SD): C(pt) mean 23.3 +/- 29.4 mm(2), EF(pt) 829.7 +/- 679.3 mm(2), AC(pt) 609.9 +/- 219.4 mm(2). In the final study, 2-factorial ANOVA showed a significant effect (p < 0.001) for the use of drainages but not for the application of PL (C(fs)ØPL 140.6 +/- 124.2 mm(2), C(fs)+PL 67.7 +/- 60.4 mm(2), EF(fs)ØPL 1,217.0 +/- 458.3 mm(2), EF(fs)+PL 1,266.8 +/- 368.3 mm(2), AC(fs)ØPL 861.7 +/- 274.8 mm(2), AC(fs)+PL 544.2 +/- 193.8 mm(2)). Post hoc test for pairwise comparisons adjusted to Bonferroni showed significant differences (p < 0.001) between all of the three pairs (C(fs) 104.1 +/- 92.3 mm(2) vs. EF(fs) 1,241.9 mm(2) +/- 413.3 mm(2); C(fs) vs. AC(fs) 702.9 mm +/- 234.3 mm(2); EF(fs) vs. AC(fs)). DISCUSSION: The final study demonstrates the adhesiogenic capacity of silicone drainage tubes in combination with anastomoses. Any protective effect of PL alone or in combination with drainages could not be shown. CONCLUSIONS: Indication for the use of drainages in standard surgical procedures should be reconsidered within the scope of their potential to cause adhesions and subsequent complications.

[Material and structure of drainages]. / Material und Struktur von Drainagen.

The long history of surgical drainages stands in contradiction to available and reliable data. As of today, closed systems made of silicone are preferable. Taking possible complications into consideration and the good results of routine operations without drainages, indication for use should be critically evaluated. Interdisciplinary research,however, offers the chance of optimizing material and surface characteristics, biostability, biocompatibility, and flow rates. New drainages with improved performance and reduced side effects may counteract the current tendency to do without.

Influence of intraperitoneal phospholipid dosage on adhesion formation and wound healing at different intervals after surgery.

BACKGROUND: Adjuvant therapy is needed to prevent adhesion formation as a major cause of postoperative morbidity and mortality. The efficacy of phospholipids (PLs) has been proven; however, information on dosage and drug safety are still outstanding. MATERIALS AND METHODS: Forty-eight Chinchilla rabbits underwent median laparotomy, abrasion of the peritoneum, jejunal anastomosis, and an electrocautery incision of the liver. The operation was completed by intraperitoneal administration of PLs in two different concentrations (30 mg/kg and 70 mg/kg body weight). In the control group, the abdomen was closed without additional treatment. Adhesion area, anastomotic bursting pressure, tensile strength of the midline incision, and healing of the liver wound were assessed on days 3, 5, 7, and 10, respectively. RESULTS: The mean areas of adhesions in the control group were slightly larger than in the PL groups after 3 days and 5 days. On day 7 and day 10, both PL groups presented with significantly smaller adhesion areas (P<0.05). In all groups, we measured equal anastomotic bursting pressures on the 3rd, 5th, and 10th postoperative days. After 7 days, the mean value of the PL 70-mg group (17.2 kPa) was significantly lower than in the other groups (control 22.1 kPa, PL 30 mg 20.7 kPa; P<0.05). The tensile strengths of the laparotomy wound measured after intervals of 5 days and 7 days were not statistically different. On day 3, it was reduced after 30 mg PL but enhanced after 70 mg PL, whereas 10 days after surgery the strength increased with the PL dosage. The inflammatory reparative response to hepatic injury, jejunal anastomosis, and midline incision was not affected by PLs as assessed by histological analysis. CONCLUSION: These results prove the efficacy of PLs in adhesion prevention in two concentrations. The findings reveal an unimpeded healing of anastomoses, laparotomy wounds, and liver incisions at different periods after surgery.

Comparison of adhesion reformation after laparoscopic and conventional adhesiolysis in an animal model.

This study set out to compare adhesion reformation after conventional and laparoscopic adhesiolysis using two different laparoscopic dissection techniques. In a first operation, 36 rabbits underwent fixation of 6 cm2 of the cecum with the serosa removed to the lateral abdominal wall to induce standardized adhesions. After 4 weeks, adhesiolysis was performed laparoscopically (n = 12) or via laparotomy (n = 12) using sharp and blunt dissection. In a third group (n = 12), laparoscopic adhesiolysis was performed using monopolar electrocautery. Outcome was assessed by incidence, extent, and localization of adhesion reformation. After conventional adhesiolysis, all rabbits developed new adhesions relative to 79% after laparoscopic adhesiolysis. The extent of reformed adhesions (median) was greater after conventional adhesiolysis than laparoscopic adhesiolysis (2725 mm2 vs 230 mm2, P < 0.001). The latter did not differ significantly from laparoscopic adhesiolysis by electrocautery (310 mm2). There were small adhesions to 3 of 72 trocar wounds, but extensive adhesions to 33% of the abdominal incisions were found in the conventional group. In this standardized experimental setting, laparoscopic adhesiolysis is associated with a significantly reduced reformation of adhesions. Different laparoscopic dissection techniques have no significant influence on the extent of adhesion reformation.

Efficacy of adhesion prevention and impact on wound healing of intraperitoneal phospholipids.

BACKGROUND: Postoperative peritoneal adhesions are a major complication of abdominal surgery. Adjuvant therapy is needed to prevent adhesion formation and subsequent sequelae. Previously published data proved the efficacy of phospholipids (PL) for this indication; however, additional information on drug safety was still outstanding. The underlying study was designed to investigate the influence of phospholipids on three different types of healing tissue. MATERIALS AND METHODS: A total of 48 Chinchilla rabbits underwent median laparotomy, standardized abrasion of the visceral and parietal peritoneum, jejunal anastomosis, and an electrocautery incision of the liver. The operation was completed by intraperitoneal administration of 10 ml/kg of either normal saline (NaCl) or phospholipids (12%). RESULTS: After 5 (NaCl 691 mm(2) vs PL 192 mm(2)) and 10 days (NaCl 625 mm(2) vs PL 88 mm(2)) the control group presented with significantly larger adhesion areas (P < 0.05). The bursting pressure of the anastomosis on the 5th (NaCl 16.1 kPa vs PL 18.2 kPa) and 10th (NaCl 19.7 kPa vs PL 18.6 kPa) postoperative days showed no statistically significant difference. The tensile strength of the laparotomy wound measured after intervals of 5 (NaCl 8.5 N cm(-1) vs PL 6.8 N cm(-1)) and 10 days (NaCl 23.0 N cm(-1) vs PL 20.2 N cm(-1)) was not statistically different either. The collagen protein ratio of anastomoses, laparotomy wounds, and liver incisions as well as the inflammatory-reparative response of the different tissues was not affected by PL. CONCLUSIONS: These results confirm the efficacy of phospholipids in adhesion prevention. The findings of uncompromised healing of anastomoses, laparotomy wounds, and liver incisions demonstrate the safety of this agent. Further data may qualify phospholipids for a clinical trial.

New adhesion formation after laparoscopic and conventional adhesiolysis: a comparative study in the rabbit.

This study aimed to compare new adhesion formation after laparoscopic and conventional adhesiolysis. In a first operation, 24 rabbits underwent fixation of deserosated cecum (6 cm2) to the lateral abdominal wall to induce standardized adhesions. After 4 weeks, adhesiolysis was performed by laparoscopy (n = 12) or laparotomy (n = 12). Outcome was assessed by the incidence, extent, and location of adhesion reformation. After conventional adhesiolysis, new adhesions developed in all the rabbits, as compared with 75% after laparoscopic adhesiolysis. The extent of newly formed adhesions was significantly reduced (p < 0.001) after laparoscopic adhesiolysis (368+/-115 mm2) as compared with conventional adhesiolysis (2434+/-245 mm2). There were no adhesions to trocar wounds, but adhesions to the abdominal incision were found in 33% of the conventional group. In a rabbit model comparing laparoscopic and conventional adhesiolysis in a standardized experimental setting, laparoscopic adhesiolysis is associated with a significantly reduced formation of new postoperative adhesions.

[Prevention of adhesions. Wish and reality]. / Adhäsionsprophylaxe. Wunsch und Wirklichkeit.

For more than a century peritoneal adhesions are being recognized as frequent sequelae following abdominal surgery. Intraoperative lesions of the mesothelial lining by abrasion, ischemia, dissication, and foreign bodies result in complaints, intestinal obstruction, female infertility, and problems during reoperations. The global increase of life expectancy and surgical procedures are leading to rising incidences of adhesion-related complications and subsequent socio-economic implications. As of today, there is no safe and efficient prophylaxis available. Scientific efforts should be aimed at a liquid substance for single intraperitoneal application which significantly reduces postoperative adhesions at reasonable cost without adverse effects on blood coagulation and wound healing.

Postoperative necrotizing soft-tissue infections of the abdominal wall.

OBJECTIVE: The aim of the underlying study was the evaluation of an aggressive surgical regimen for treatment of postoperative necrotizing soft-tissue infection (NSTI). METHODS: Eight patients with postoperative NSTI of the abdominal wall after emergency (n=6) and elective (n=2) surgery were reviewed over a 9-year period. RESULTS: Initially, three patients presented with general peritonitis. Cultured swabs from the necrotic tissue revealed three to four different types of bacteria in each patient. The mean interval between the primary operation and clinical symptoms of NSTI was 63.0 h. Control of NSTI and intra-abdominal infection was attained by scheduled re-operations on a daily basis accounting for three to six re-interventions in each patient. Temporary closure of the abdominal wall by absorbable polyglactid-acid mesh was used in six cases. Mean hospital stay was 65.3 days (18-110 days). Two of the eight patients died from cardiac arrest and multiple organ failure, respectively. CONCLUSIONS: Rapid diagnosis and onset of treatment is accomplished by the surgeons' knowledge of this disease and a close follow-up of the patients in an intensive care unit.

Intraperitoneal transplantation of isologous mesothelial cells for prevention of adhesions.

OBJECTIVE: To study the effect of transplantation of mesothelial cells on the formation of adhesions after peritoneal abrasion. DESIGN: Animal study. SETTING: Teaching hospital, Germany. ANIMALS: 30 isologous eight-week old Lewis rats to allow for harvesting of the greater omentum from a separate group. INTERVENTIONS: The first group (n = 10) served as mesothelial cell donors. The other animals had laparotomy and induction of adhesions by standardised abrasion of the peritoneum. The trial group (n = 10) were given a suspension of 10(6) mesothelial cells/100 g body weight intraperitoneally and the control group (n = 10) an equal volume of culture medium. After 10 days the animals were killed. MAIN OUTCOME MEASURES: Measurements of the areas of adhesions by computer aided morphometry. RESULTS: The trial group developed a mean (SD) adhesion area of 122.7 (176.7) mm2, and the controls 310.5 (179.1) mm2. The corresponding medians (range) were 51.2 (0-547.1) and 274.3 (100.6-575.4). Transplantation of mesothelial cells resulted in a significant reduction in adhesion formation (Wilcoxon test, p<0.01). CONCLUSION: Intraperitoneal transplantation of mesothelial cells is an effective way of reducing the formation of adhesions.

Value of intravenous cholangiography prior to laparoscopic cholecystectomy.

We performed a retrospective study on 163 patients for evaluation of the benefit of intravenous cholangiography prior to laparoscopic cholecystectomy. Radiographic evaluation of the various areas of the biliary system was classified regarding resolution of anatomic structures: well detailed (excellent), impaired image but reliable interpretation possible (good), insufficient contrast with limited assessment (poor), no reliable judgment possible (insufficient). The common bile duct could be described as "good" in 96.3%, whereas the cystic duct could be described as "good" in only 54.6%. Concrements of the gallbladder were recognized in 72.4%, and common bile duct stones were diagnosed in only two of three patients. A distal junction of the cystic duct was found in nine cases, but there was no influence on the following operative procedure. Only one of two patients with a short cystic duct was identified. We found no improvement after routine use of intravenous cholangiography concerning the evidence of common bile duct stones or the avoidance of lesions of the common bile duct. Hence routine use of intravenous cholangiography prior to laparoscopic cholecystectomy is not justified.

[Artificial pressure increase in subcutaneous abscess with evidence of general systemic reaction]. / Artifizielle Drucksteigerung im subkutanen Abszess mit Nachweis einer systemischen Allgemeinreaktion.

Abscess is customarily thought of as a collection of a large number of microorganisms, inflammatory cells and necrotic debris separated from the surrounding tissue by a fibrous capsule. Modern work focussed attention on more physico-chemical parameters in abscess pathogenesis. Recent experiences from animal models underline the impact of abscess pressure and bio-physicochemical parameters in the "abscess compartment" for systemic spreading. Artificial raising of abscess-pressure in pigs up to 80 mmHg was followed by increase of temperature and heartbeat rate and decrease of median arterial pressure. Elevated levels of TNF alpha, IL-1 and positive blood cultures support the theory of abscess pressure as a most important variable in abscess formation. We conclude that abscess pressure may play a pivotal role in systemic spreading of the primarily localized process.

[Epidemiology of appendicitis]. / Epidemiologie der Appendicitis.

Epidemiological data reveal a decline in the incidence of appendicitis and appendectomy in the industrialized countries. A peak is found in adolescents aged 10-19 years; however, the highest rates of perforation are reported for the extremely young and old age groups. The elevated rate of appendectomies without histological evidence of acute inflammation, especially in young women, and the high perforation ratio in small children and elderly patients reflect poor diagnostic accuracy. Analysis of the epidemiological data does not allow for an unequivocal conclusion regarding the etiopathogenesis of acute appendicitis.

True carcinosarcoma of the colon. Case report.

A second case of true carcinosarcoma of the colon is reported. A 79-year-old women was diagnosed as having an obstructing tumour of the caecum and liver metastases in both lobes. Histological examination of operative specimen from a right hemicolectomy revealed malignant epithelial and mesenchymal components. Despite postoperative chemotherapy, the patient died of liver failure resulting from extensive metastatic growth.

Low-dose, single-shot perioperative antibiotic prophylaxis in colorectal surgery.

Reductions of frequency of administration and dosage of antibiotic agents used in colorectal surgery may lower costs and the occurrence of adverse side effects. In a prospective randomized trial we evaluated two single-short regimens, a low dose of 1 g cefotiam against a standard dose of 2 g cefotiam, both in combination with 500 mg metronidazole. The low-dose group had twice the number of patients with wound sepsis (4 of 30) than the group receiving the standard antibiotic regimen (2 of 30). Two hours after infusion, the antibiotic concentrations in samples of serum, subcutaneous fatty tissue, and colonic wall of those patients receiving 1 g cefotiam were < 1 mg/l. The concentrations after administration of 2 g cefotiam were higher, as expected, and without any adverse side effects. In conclusion, we prefer infection prophylaxis by the standard dose of 2 g cefotiam plus 500 mg metronidazole in colorectal surgery.

Ruptured hepatic angiolipoma in tuberous sclerosis complex.

Tuberous sclerosis complex (TSC) may be associated with hepatic angiomyolipoma. In contradistinction to renal angiomyolipoma this lesion is rare, and nontraumatic hemorrhage has not so far been described. This is the first report of a spontaneously ruptured, surgically treated and histologically verified, hepatic angiomyolipoma in TSC. Anomalies of the vessel walls and consequently the hazard of bleeding are known to increase with the diameter of the tumor in other localizations. It is concluded that in cases with rapid tumor growth and marked vessel anomalies elective surgery should be considered.

Prevention of postoperative adhesions by single intraperitoneal medication.

Postoperative adhesions account for a significant morbidity after abdominal, gynecological, or cardiac surgery. A large number of compounds have been suggested to prevent such adhesions, but none is generally accepted. We have compared eight different substances that could be beneficial for the prevention of postoperative adhesions in a new standardized rabbit model with measurement of the areas of adhesion. In 10 groups of 20 rabbits an area of abrasion of the serosa of the ileum, the appendix, and the abdominal wall measuring 10,000 mm2 was created by an emery piston during celiotomy. The controls received no medication. The treatment groups received a single intraperitoneal administration of 1 ml per 100 g body wt of normal saline (NaCl), 5 mg taurolidine (T), 0.5 U plasmin/300 U DNase (PD), 2000 IU streptokinase/500 IU streptodornase (SS), 7 mg phosphatidylcholine (PC), 4 mg hyaluronic acid (HA), 7 mg sphingolipid (SL), 7 mg galactolipid (GL), or 0.5 ml tetrachlorodecaoxide (TCDO), respectively. Ten days later the extent of adhesions was quantified by morphometry. The total area of adhesions (+/- SEM) was found to be 1998 +/- 124 mm2 in controls. The application of NaCl reduced the adhesions to 1368 +/- 58 mm2, of T to 1012 +/- 48 mm2, of PD to 673 +/- 33 mm2, of SS to 360 +/- 44 mm2, of PC to 335 +/- 84 mm2, of HA to 328 +/- 76 mm2, of SL to 278 +/- 80 mm2, of GL to 261 +/- 67 mm2, and of TCDO to 240 +/- 45 mm2. The effects of PD, SS, PC, HA, SL, GL, and TCDO were significant in comparison to controls and NaCl. Our experimental data suggest that the two new lipid substances, SL and GL, are the most likely candidates for routine clinical use in the prevention of postsurgical adhesions.

[Prevention and therapy of intra-abdominal adhesions. A survey of 1,200 clinics in Germany]. / Prophylaxe und Therapie intraabdomineller Adhäsionen. Eine Umfrage an 1200 Kliniken in Deutschland.

A survey of 1200 hospitals in Germany was undertaken to estimate the current standards of prevention and treatment of postoperative peritoneal adhesions. The 751 (62.2%) evaluated questionnaires showed a representative distribution according to postal zones and annual laparotomies. The rate of coeliotomies for adhesional bowel obstruction is 2.6%. Starch-powdered gloves are used in 54.2% and washed before operating in 69.3%. Dry swabs and towels are used in 60.7 and 22.5%, respectively. Most of the surgeons suture the peritoneum. Adhesions are divided in patients with respective symptoms but without intestinal obstruction by 32.6% and during laparotomies for non-adhesion-related diseases by 20.4%. Long intestinal tubes and plication procedures are applied by 43.9 and 33.7%, respectively. Medication is administered for routine prophylaxis of adhesion by 6%, for prevention of recurrencies by 17.2%. Although it has been revealed that adjuvant measures for prevention of adhesions are needed, as of today, no regimen has proofed its efficacy and gotten accepted for clinical usage.