Reduction of peritoneal trauma by using nonsurgical gauze leads to less implantation metastasis of spilled tumor cells

OBJECTIVES: To evaluate whether infliction of peritoneal trauma would promote tumor cell adherence to damaged peritoneal surfaces; to investigate whether peritoneal damage could promote tumor growth of extraperitoneal tumors; and to evaluate whether the amount of trauma correlated with the degree of tumor cell adherence and local and distant tumor growth. BACKGROUND DATA: After potentially curative resection of colorectal carcinoma, the most common site for recurrence is locoregional. We previously demonstrated that surgical trauma induces a cascade of events leading to adhesion formation. The same mechanisms may be responsible for improved tumor cell adherence and growth facilitation in early local recurrence. METHODS: A reproducible rat model was used in which peritoneal damage was inflicted by standardized rubbing of the peritoneum with surgical gauzes of different texture. In the first experiment, tumor cell adherence and growth at traumatized and nontraumatized peritoneal sites were assessed semiquantitatively 3 weeks after perioperative intra-abdominal injection of CC-531 tumor cells. In the second experiment, the effect of peritoneal trauma on ectopic tumor growth was investigated (CC-531 implanted under the renal capsule). In the final experiment, we evaluated how soon after peritoneal traumatization tumor cell adhesion and growth-promoting factors were active and whether they could be passively transferred to naive nontraumatized abdominal cavities. RESULTS: A significant correlation between the amount of peritoneal trauma and the degree of tumor take at damaged peritoneal surfaces was found (p < or = 0.018). Tumor take at remote peritoneal sites not directly traumatized was also significantly higher after severe trauma than after moderate trauma of the peritoneum (p < or = 0.005). In addition, a significant correlation between the degree of peritoneal trauma and the growth of ectopic tumors under the renal capsule was observed (p < or = 0.009). The final experiment demonstrated that within a few hours after infliction of peritoneal trauma, tumor growth-promoting effects could be passively transferred to naive recipients. CONCLUSIONS: Surgical trauma is an important factor in the promotion of local recurrence. The enhancing effect of trauma is not restricted to the inflicted site but rather has a generalized character. Avoidance of unnecessary surgical trauma by using gentle techniques and materials is therefore indicated

Scavenging of reactive oxygen species leads to diminished peritoneal tumor recurrence

Previously, we demonstrated that RBCs inhibit the recurrence of perioperatively spilled tumor cells. The aim of this study was to identify on which RBC component(s) the inhibitory effect is based. By using a cell-seeding model in rats, the effect of RBC-related antioxidant scavengers [hemoglobin, catalase, and superoxide dismutase (SOD)] on peritoneal tumor recurrence was investigated. i.p. injection of hemoglobin caused 45% more tumor load (P < 0.0001). At least 40% inhibition of tumor recurrence was achieved with the use of catalase or SOD (P < 0.05). Combining SOD and catalase did not lead to additional inhibition of tumor recurrence. Inhibition of the overwhelmin

Effects of thyroid status and thyrostatic drugs on hepatic glucuronidation of lodothyronines and other substrates in rats - Induction of phenol UDP-glucuronyltransferase by methimazole

Glucuronidation of iodothyronines in rat liver is catalyzed by at least three UDP-glucuronyltransferases (UGTs): bilirubin UGT, phenol UGT, and androsterone UGT. Bilirubin and phenol UGT activities are regulated by thyroid hormone, but the effect of thyroid status on hepatic glucuronidation of iodothyronines is unknown. We examined the effects of hypothyroidism induced by treatment of rats with propylthiouracil (PTU) or methimazole (MMI) or by thyroidectomy as well as the effects of T4-induced hyperthyroidism on the hepatic UGT activities for T4, T3, bilirubin, p-nitrophenol (PNP), and androsterone. Bilirubin UGT activity was increased in MMI- or PTU-induced hypothyroid and thyroidectomized rats, and decreased in hyperthyroid animals. T4 and, to a lesser extent, T3 UGT activities were increased in MMI- or PTU-induced hypothyroid rats, and T4 but not T3 glucuronidation also showed a significant increase in thyroidectomized rats. T4 but not T3 UGT activity was slightly decreased in hyperthyroid rats. While PNP UGT activity was decreased in thyroidectomized rats and increased in hyperthyroid animals, it was also markedly increased by MMI and slightly increased by PTU-induced hypothyroidism. In T4-substituted rats, MMI did not affect T4, T3, bilirubin and androsterone UGT activities but again strongly induced PNP UGT activity, indicating that this represented a direct induction of PNP UGT by the drug independent of its thyrostatic action. Androsterone UGT activity was hardly affected by thyroid status. Our results suggest a modest, negative control of the hepatic glucuronidation of thyroid hormone by thyroid status, which may be mediated by changes in bilirubin UGT activity. To our knowledge, this is the first report of the marked induction of a hepatic enzyme by MMI, which is not mediated by its thyroid hormone-lowering effect

Intrathymic injection of alloantigen may lead to hyperacute rejection and prolonged graft survival of heart allografts in the rat

The recent reports describing the beneficial effect of intrathymic (IT) inoculation of donor antigen on subsequent allograft survival prompted us to study this phenomenon in the high responder WAG to BN rat strain combination as well as in the low-responder BN to WAG combination. Previously in the WAG to BN model, we found that a donor-specific blood transfusion (DST) given 1 week before the heterotopic heart transplantation led to accelerated rejection in 5 days, whereas in the reverse model, a DST consistently led to marked prolongation of graft survival. These opposing phenomena led us to determine whether the effects of DST in the two rat strain combinations mentioned above would also occur after IT injection of donor type cells.[...]In conclusion we demonstrated that, similarly as following DST, the ability to induce prolonged acceptance of heart allografts by IT injection of donor-type cells is highly dependent on the donor-host combination used. The remarkable finding that IT injection can also lead to sensitization and even hyperacute rejection indicates that caution should be exercised with this ambiguous procedure

Intrathymic injection of alloantigen may lead to hyperacute rejection and prolonged graft survival of heart allografts in the rat

The recent reports describing the beneficial effect of intrathymic (IT) inoculation of donor antigen on subsequent allograft survival prompted us to study this phenomenon in the high responder WAG to BN rat strain combination as well as in the low-responder BN to WAG combination. Previously in the WAG to BN model, we found that a donor-specific blood transfusion (DST) given 1 week before the heterotopic heart transplantation led to accelerated rejection in 5 days, whereas in the reverse model, a DST consistently led to marked prolongation of graft survival. These opposing phenomena led us to determine whether the effects of DST in the two rat strain combinations mentioned above would also occur after IT injection of donor type cells.[...]In conclusion we demonstrated that, similarly as following DST, the ability to induce prolonged acceptance of heart allografts by IT injection of donor-type cells is highly dependent on the donor-host combination used. The remarkable finding that IT injection can also lead to sensitization and even hyperacute rejection indicates that caution should be exercised with this ambiguous procedure