povidone-iodine and Adenocarcinoma

Port site metastases can occur when free viable tumor cells implant at trocar wounds. Irrigation of port sites with cytotoxic agents has been suggested to prevent port site metastases. The objective of this study is to assess whether tumor growth at port sites can be reduced by irrigation of these port sites.. WAG rats were insufflated with CO(2) for 20 minutes and 5 x 10(5) CC531 tumor cells were injected intraperitoneally. Port sites were irrigated after completion of the pneumoperitoneum with povidone-iodine, a mixture of taurolidine and heparin, or sodium chloride. Controls did not undergo any irrigation of port sites. In experiment 1, all 16 rats had all 4 irrigation modalities. In experiment 2, four groups of 20 rats had one type of irrigation on two trocar wounds. Tumor growth was evaluated 4 weeks after the procedure.. No difference in tumor growth at trocar wounds was found between any type of irrigation and controls in both experiments.. In this experimental model, no beneficial or adverse effects of irrigation of port sites could be shown.

Topics: Adenocarcinoma; Animals; Heparin; Laparoscopy; Male; Neoplasm Seeding; Neoplasm Transplantation; Pneumoperitoneum, Artificial; Povidone-Iodine; Punctures; Rats; Rats, Inbred Strains; Sodium Chloride; Taurine; Therapeutic Irrigation; Thiadiazines

Exfoliated or soiled free malignant cells have serious consequences in patients undergoing gastrointestinal cancer surgery. The present study evaluates the toxicity and efficacy of cytotoxic agents in the prevention of cell seeding and tumor growth in the peritoneal cavity in an experimental model.. Mtln3 adenocarcinoma cell viability was tested in vitro using the trypan blue exclusion test after incubation with povidone-iodine or chlorhexidine. In vivo, Fischer rats were inoculated with 10(5) or 10(6) cells followed by peritoneal lavage with physiological saline, chlorhexidine 0.02 percent, povidone-iodine low molecular weight 1 percent or povidone-iodine high molecular weight 1 and 2 percent in different quantities and incubation times.. Chlorhexidine 0.02 percent and povidone-iodine low molecular weight 1 percent or high molecular weight 2 percent, killed over 98 percent of 10(5) or 10(6) tumor cells in vitro. Povidone-iodine low molecular weight 1 percent and high molecular weight 2 percent were toxic and lethal when 5 ml were applied in the peritoneal cavity three times for five minutes. Chlorhexidine 0.02 percent applied after inoculation of 10(5) or 10(6) cells, reduced the tumor development only to 70 and 80 percent. Application of 5 ml povidone-iodine 1 percent low molecular weight or high molecular weight, three times for one and five minutes, after inoculation of 10(6) cells did not change the tumor take. However, inhibition of Mtln3 cells to form metastases was observed. When povidone-iodine low molecular weight 1 percent was used three times for one minute after 10(5) tumor cells were "soiled", no toxicity was observed and the tumor take was reduced to 30 percent (P < 0.05).. Povidone-iodine toxicity proved to be a major issue in vivo. However, povidone-iodine low molecular weight 1 percent was safe when used for short periods and very effective when a limited number of tumor cells was inoculated. The use of cytotoxic agents to prevent recurrent disease caused by tumor cell seeding in patients seems to make sense only when the "inoculum size" of exfoliated or soiled cancer cells is limited.

Topics: Adenocarcinoma; Animals; Chlorhexidine; Disease Models, Animal; Female; Male; Neoplasm Recurrence, Local; Neoplasm Seeding; Neoplasms, Experimental; Peritoneal Lavage; Povidone-Iodine; Rats; Rats, Inbred F344; Rectal Neoplasms; Sensitivity and Specificity; Treatment Outcome

The development of port-wound tumor recurrences has raised questions regarding the safety of laparoscopic methods for the resection of malignancies. The cause and the incidence of abdominal-wall tumor recurrences remain unknown. It is also not clear how to avoid or lower the incidence of port-tumor recurrences. The purpose of the current study was to determine the impact of abdominal irrigation with povidone-iodine on the port-wound tumor incidence in a murine model.. A splenic tumor model was used for this study. To establish splenic tumors, female BALB/c mice (N = 48) were given subcapsular splenic injections of a 0.1 ml suspension containing 10(5) C-26 colon adenocarcinoma cells via a left-flank incision at the initial procedure. Seven days later, the animals with isolated splenic tumors (100 percent) were randomly assigned to one of three groups: 1) control, 2) saline irrigation (saline), or 3) povidone-iodine irrigation. All animals underwent laparoscopic mobilization of the spleen using a three-port technique, intra-abdominal crushing of the tumor, followed by an extracorporeal splenectomy via a subcostal incision. No irrigation was performed for control group animals. In the saline irrigation group, the subcostal incision was closed and pneumoperitoneum was re-established. The abdominal cavity was irrigated with 5 ml of normal saline for 60 seconds before instrument removal. In the povidone-iodine irrigation group, similar abdominal irrigation was performed, using 0.25 percent povidone-iodine. Attempts were made to recover completely the irrigation for both irrigation groups. Seven days after the splenectomy, animals were killed and inspected for abdominal-wall tumor implants.. There were significantly more animals with at least one port-tumor recurrence in the control group than in the povidone-iodine group (P = 0.007). Although not statistically significant, the number of animals with port-wound tumors was higher in the saline group than in the povidone-iodine group (P < 0.08). There was no significant difference between the saline group and the control group. When each port site was considered independently, the incidence of port-wound tumors (number of ports with tumors per total number of ports) was significantly lower in the povidone-iodine group than in both the control (P = 0.00001) and saline groups (P = 0.03). The incidence of port-wound tumors was also significantly lower in the saline group compared with the control group incidence (P = 0.03).. Abdominal irrigation with dilute povidone-iodine solution significantly reduced the number of animals with port-tumor recurrences. Abdominal irrigation with saline was also effective in reducing the incidence of port-wound tumor formation when each port was considered separately. However, povidone-iodine irrigation was much more effective than saline irrigation in preventing port-wound tumor formation.

Topics: Adenocarcinoma; Animals; Anti-Infective Agents, Local; Evaluation Studies as Topic; Female; Laparoscopy; Mice; Mice, Inbred BALB C; Neoplasm Seeding; Pilot Projects; Povidone-Iodine; Random Allocation; Splenectomy; Splenic Neoplasms; Therapeutic Irrigation; Tumor Cells, Cultured

A generally accepted approach to prevent tumor implantation with laparoscopic surgery does not exist. Alternative gases in combination with intraperitoneal instillation of different antiadherent or cytotoxic agents have not been evaluated.. The effect of taurolidine, heparin, and povidone-iodine on the growth of colon adenocarcinoma DHD/K12/TRb was measured in rats undergoing laparoscopy with carbon dioxide (n = 40), helium (n = 40), or xenon (n = 40). In the procedure, 10(4) tumor cells were administered intraperitoneally, and pneumoperitoneum was established over 30 min at 8 mmHg with the different gases. The rats additionally received intraperitoneal instillation with one of the following: 1 ml of Ringer's solution, 1 ml of 0.5% taurolidine, 1 ml 0.5% taurolidine with heparin (10 U/ml), or 1 ml 0.25% of povidone-iodine. Tumor growth was measured after 4 weeks.. Median intraperitoneal tumor weight was lower in rats receiving taurolidine (CO(2): 10 mg; helium: 50 mg; xenon: 39.5 mg) or taurolidine with heparin (CO(2): 4 mg; helium: 4.5 mg; xenon: 46.5 mg) in all gas groups than in the control groups (CO(2): 427 mg; helium: 268 mg; xenon: 345 mg) (p < 0.001). Whereas povidone-iodine caused significantly lower tumor growth in the CO(2) group (56.5 mg) (p < 0.01), the combination of helium (145 mg) and xenon (457 mg) with povidone-iodine produced no reduction of tumor growth as compared with the control groups (helium: 268 mg; xenon: 345 mg).. Taurolidine and taurolidine with heparin significantly inhibit intraperitoneal tumor growth, with different gases used for pneumoperitoneum. Only povidone-iodine caused significant decrease of tumor growth in combination with CO(2). The combination of xenon and povidone-iodine should not be used in patients with cancer because of increased tumor growth.

Topics: Adenocarcinoma; Animals; Anti-Infective Agents; Anticoagulants; Carbon Dioxide; Colonic Neoplasms; Heparin; Instillation, Drug; Laparoscopy; Male; Neoplasm Seeding; Pneumoperitoneum, Artificial; Povidone-Iodine; Rats; Taurine; Thiadiazines; Tumor Cells, Cultured

Therapeutic strategies to prevent port site recurrences in laparoscopy surgery of malignancies have not been investigated until now.. The effects of taurolidine, heparin, and povidone iodine on the growth of rat and human colon adenocarcinoma as well as gallbladder carcinoma were investigated in vitro. Furthermore, cytokine release of growth-stimulating IL-1beta by peritoneal macrophages was measured after incubation with carbon dioxide and additional incubation with the different agents. In the third experiment, prevention of intra- and extraperitoneal metastases by intraperitoneal instillation of the different agents during laparoscopy was investigated in a colon carcinoma model in the rat. Tumor cells were administered intraperitoneally in 100 rats, and pneumoperitoneum (8 mm Hg) was established over 30 min with carbon dioxide. Rats received either tumor cells, cells + heparin, cells + povidone iodine, cells + taurolidine, or cells + taurolidine + heparin.. In vitro, tumor cell growth decreased after incubation with taurolidine, taurolidine/heparin, and povidone iodine. Cytokine release was stimulated by incubation with carbon dioxide and could only be suppressed by incubation with taurolidine in vitro. In vivo, intraperitoneal tumor weight was lower in rats receiving heparin (251 +/- 153 mg) and povidone iodine (134 +/- 117 mg) compared to the control group (541 +/- 291 mg), but even less when taurolidine (79 +/- 82 mg) or taurolidine/heparin (18.3 +/- 30 mg) were instilled.. Heparin slightly inhibits intraperitoneal tumor growth in vivo, while povidone iodine and taurolidine cause a significant decrease in tumor cell growth in vitro as well as intraperitoneal tumor growth in vivo. Cytokine release of peritoneal macrophages is only suppressed by taurolidine. Total tumor take and trocar metastases are only suppressed by taurolidine and taurolidine/heparin.

Topics: Adenocarcinoma; Animals; Anti-Infective Agents, Local; Carbon Dioxide; Colonic Neoplasms; Gallbladder Neoplasms; Heparin; Humans; Interleukin-1; Laparoscopy; Macrophages, Peritoneal; Male; Neoplasm Metastasis; Neoplasm Seeding; Peritoneal Cavity; Povidone-Iodine; Rats; Rats, Inbred Strains; Taurine; Thiadiazines; Tumor Cells, Cultured