Evaluation of the Effectiveness of Peritoneal Adhesion Prevention Devices in a Rat Model.

BACKGROUND: Abdominal operations are followed by adhesions, a prevalent cause of abdominal pain, and the most frequent cause for bowel obstruction and secondary female infertility. This rat study addresses adhesion prevention capability of Adept(®), Interceed(®), Seprafilm(®), and a novel device, 4DryField(®) PH which is provided as powder and generates its effect as gel. METHODS: Sixty-eight male Lewis rats had cecal abrasion and creation of an equally sized abdominal wall defect, and were grouped randomly: A control group without treatment (n=10); two groups treated with 4DryField(®) PH using premixed gel (n=15) or in-situ gel technique (n=16); one group each was treated with Seprafilm(®) (n=8), Interceed(®) (n=9), or Adept(®) (n=10). Sacrifice was on day 7 to evaluate incidence, quality, and quantity of adhesions, as expressed via adhesion reduction rate (AR). Histologic specimens were evaluated. Statistical analyses used ANOVA and unpaired t-tests. RESULTS: 4DryField(®) PH significantly reduced incidence and severity of adhesions both as premixed gel (AR: 85.2%) and as in-situ made gel (AR: 100%), a comparison between these two application techniques showed no differences in efficacy. Seprafilm(®) did not reduce incidence but severity of adhesions significantly (AR: 53.5%). With Interceed(®) (AR: 3.7%) and Adept(®) (AR: 16.1%) no significant adhesion-reduction was achieved. Except for inflammatory response with Interceed(®), histopathology showed good tissue compatibility of all other devices. CONCLUSION: 4DryField(®) PH and Seprafilm(®) showed significant adhesion prevention capabilities. 4DryField(®) PH achieved the highest adhesion prevention effectiveness without restrictions concerning mode of application and compatibility and, thus, is a promising strategy to prevent abdominal adhesions.

Impairment of the Peritoneal Surface as a Decisive Factor for Intestinal Adhesions in Intraperitoneal Onlay Mesh Surgery - Introducing a New Rat Model.

BACKGROUND: Meshes implanted intraperitoneally are known to cause adhesions potentially resulting in complications such as chronic pain, enterocutaneous fistula, or mesh infection. This study introduces a model for investigation of intestine-to-mesh adhesions and evaluates as to whether missing of visceral peritoneum is causative. METHODS: In 18 rats, rectangular 1.5 x 2 cm patches of an uncoated polypropylene mesh (Ultrapro(®)) were sewn to the inner abdominal wall next to the cecum. Additionally, a meso-suture ensured contact between cecum and mesh. Rats were assigned to 2 groups: in 8 rats the peritoneum was left intact, in 10 the cecum was depleted from peritoneum with abrasion. Sacrifice was on day 7. Macroscopic evaluation used two adhesion scores. Specimens were evaluated microscopically, statistical analyses employed student's t-test. RESULTS: On day 7, rats with mesh implantation combined with locally de-peritonealization by cecal abrasion mostly showed severe cecum-to-mesh agglutination (mean Lauder score 92%, mean total Hoffmann score 90%), whereas meshes of most animals without cecal abrasion only had some coverage with intraabdominal fat (33%, 24%; p = 0.0002). Histological work-up showed adequate wall ingrowth of mesh in all rats. In animals with cecal abrasion, meshes were mostly adhesive with cecal wall. However, when the peritoneum of cecum was unimpaired, abdominal wall above the mesh as well as cecum usually revealed sub-peritoneal tissue and a mono-layer cell coverage as seen in normal peritoneum. CONCLUSION: This study introduces a model mimicking a clinical situation of e.g. hernia repair by intraperitoneally implanted meshes when mesh has contact with normal and with de-peritonealized intestine. The model might be useful for testing mesh types and coatings as well as other devices for their efficacy in adhesion prevention. The high adhesion scores of rats with local de-peritonealization compared with the low scores of animals with intact peritoneum indicate that the integrity of intestinal peritoneum is a decisive factor for adhesion formation.

Regulatory T cells in peripheral blood, lymph node, and thyroid tissue in patients with medullary thyroid carcinoma.

BACKGROUND: Immunological response of the human body is controlled by the suppressive characteristics of regulatory T cells (Tregs). In various diseases a change in the number of Tregs is evident. For example, whereas Tregs are reduced in auto-immunological processes, an increase of Tregs is found with various malignant tumors. Regarding medullary thyroid carcinoma (MTC) no such studies have been performed to date. METHODS: Expression of CD4 and CD25 in CD45+ leukocytes from blood and lymph nodes was studied by flow cytometry in patients with MTC and patients with benign goiter. We also examined the marker forkhead box P3 (FoxP3), an intracellular transcription factor, which is supposed to be the most specific marker for Tregs. Immunohistochemical staining for FoxP3 was performed on lymph node and thyroid tissue. RESULTS: The number of FoxP3+ lymphocytes in peripheral blood was significantly higher in patients with MTC than in controls (p = 0.02). This result was confirmed immunohistochemically in lymph node and thyroid tissue, as well as in carcinoma tissue. No difference in CD4+CD25+ lymphocytes was observed between the two groups. After clinical staging (International Union against Cancer-UICC-stages) of MTC patients, triplication of FoxP3+ lymphocytes could be observed from MTC < UICC II to MTC > UICC II. CONCLUSIONS: An increase of FoxP3+ lymphocytes could be shown in peripheral blood of patients with MTC but not in patients with benign goiter; this increase also correlates with findings in lymph nodes and thyroid gland. The number of FoxP3+ cells correlated with the patients' prognosis. Therefore, FoxP3+ lymphocytes are a good diagnostic criterion for malignancy in patients with medullary thyroid carcinoma, and their presence at staging may influence therapeutic decisions.