Search

Background: The pathophysiology of intra-abdominal adhesions has not been studied extensively. The aim of this study was to elucidate the molecular mechanisms underlying adhesion formation in a murine model and in patients undergoing hepatectomy., Methods: Partial hepatectomy was performed using bipolar forceps in mice. Wild-type mice, antibodies to CD4 and interferon (IFN) γ, IFN-γ, natural killer T (NKT) cells and plasminogen activator inhibitor (PAI) 1 knockout (KO) mice were used. Recombinant hepatocyte growth factor (HGF) was tested for its ability to prevent adhesions. Liver specimens were obtained during surgery from patients undergoing hepatectomy. Adhesion formation was evaluated using a scoring system that ranged from 0 (no adhesions) to 5 (severe adhesions). Levels of IFN-γ and PAI-1 mRNA, and protein concentration of PAI-I were measured, and fluorescence immunostaining was performed., Results: Adhesion formation depended on IFN-γ produced by NKT cells, and NKT KO mice developed few adhesions (mean(s.d.) 1·7(0·3) versus 4·6(0·4) in wild-type mice; P = 0·037). In wild-type mice, the level of PAI-1 mRNA increased after hepatectomy, followed by a decrease in the tissue plasminogen activator (tPA) mRNA level. Adhesion formation was inhibited completely in PAI-1 KO mice (0(0) versus 4·1(0·8) in wild-type mice; P = 0·002). HGF inhibited formation of abdominal adhesions after hepatectomy by reducing IFN-γ and PAI-1 levels, and increasing tPA levels compared with those in mice treated with phosphate-buffered saline (P < 0·001, P = 0·002 and P = 0·035 respectively). In human liver specimens, NKT cells accumulated in the liver after hepatectomy, and PAI-1 expression was increased 5·25-fold (P = 0·030)., Conclusion: IFN-γ is a key molecule for abdominal adhesion formation after hepatectomy, acting via the reciprocal balance of PAI-1 and tPA. This molecular mechanism may also regulate adhesion formation in patients following hepatectomy. HGF inhibited formation of adhesions by regulating IFN-γ and PAI-1, suggesting that it may be an important target for prevention of adhesions after hepatectomy. SURGICAL RELEVANCE: Postoperative intra-abdominal adhesions can be asymptomatic or cause significant morbidity and mortality. Adhesion formation after hepatectomy has not been studied extensively. In the present study, the molecular mechanisms underlying intra-abdominal adhesions after hepatectomy were investigated in a murine model and in patients. Interferon (IFN) γ produced by natural killer T cells is a key molecule for adhesion formation after hepatectomy in mice, acting via the reciprocal balance between plasminogen activator inhibitor (PAI) 1 and tissue plasminogen activator, the pivotal factors in fibrinolytic activity. This mechanism was also involved in the regulation of adhesions in human tissue samples. Hepatocyte growth factor (HGF) strongly inhibited adhesion formation by regulating IFN-γ and PAI-1. These results indicate that IFN-γ and PAI-1 are possible therapeutic targets, and HGF could prevent postoperative adhesion formation after hepatectomy., (© 2014 BJS Society Ltd. Published by John Wiley & Sons Ltd.)

Study Question: Is the occurrence of pelvic pain in women with ovarian endometrioma associated with coexisting peritoneal lesions (PLs)?, Summary Answer: Pelvic pain in women with ovarian endometrioma is usually associated with coexisting PLs. An increased tissue inflammatory reaction with elevated prostaglandin (PG) production may be responsible for the generation of pain., What Is Known Already: Severe pelvic pain in women with ovarian endometrioma is reported to be associated with deeply infiltrating endometriosis. However, information on pelvic pain in women with ovarian endometriosis with and without coexistent peritoneal superficial lesions is limited., Study Design, Size and Duration: Retrospective clinical study with case-controlled biological research using prospectively collected tissue samples derived from women with and without endometriosis and their retrospective evaluation., Participants/materials, Setting, Methods: We performed a retrospective cohort study conducted in 2988 cases who had laparoscopic surgery for indications of ectopic pregnancy, tubal infertility and other benign gynecologic diseases. We analyzed the occurrence of pelvic pain in the cases with ovarian endometrioma according to the distribution of coexisting PLs and pattern of intrapelvic adhesions. Inflammatory reaction of eutopic and ectopic endometria was measured by immunoreaction to macrophage marker, CD68. The tissue expression of cyclooxygenase (COX) 2 was examined by immunohistochemistry and tissue concentrations of PG F2α were measured by ELISA., Main Results and the Role of Chance: Among the 2988 surgical cases, 350 (11.7%) were found to have ovarian endometrioma at laparoscopy. Coexisting PLs were present in 269 of these women and in this group 85.4% of cases experienced pelvic pain and 14.6% had no pain. In contrast, among the 81 women with ovarian endometrioma only, 38.3% cases experienced pelvic pain and 61.7% cases had no pain and the difference between the groups was statistically significant (P < 0.01). The infiltration of CD68-immunoreactive macrophages was significantly higher in the eutopic and ectopic endometria of women with peritoneal endometriosis than in ovarian endometrioma. The tissue expression of COX2 and levels of PGF2α were significantly higher in both the eutopic and ectopic endometria derived from women with peritoneal endometriosis than in similar tissues derived from women with ovarian endometrioma., Limitations, Reasons for Cautions: Lack of evaluation in the detection of general or disseminated deeply infiltrating endometriosis in the pelvic cavity could be a bias or limitation in this study. Further multicenter prospective studies are needed to strengthen our current findings., Wider Implications of the Findings: Our findings may provide some new insights to understand the physiopathology of pelvic pain in women with ovarian cystic endometriosis and may hint at proper surgical manipulation to prevent the recurrence of pelvic pain in these women., Study Funding/competing Interest(s): This work was supported by Grants-in-Aid for Scientific Research from the Ministry of Education, Sports, Culture, Science and Technology of Japan. There is no conflict of interest related to this study., Trial Registration Number: Not applicable.

Since the introduction of percutaneous epicardial access for the purpose of mapping and ablation of cardiac arrhythmias, this technique has become an important adjunct and at times the preferred approach to treat certain cardiac arrhythmias. In addition, this approach is currently also being considered for a number of other cardiovascular applications such as epicardial pacing, left atrial appendage ligature occlusion, etc. The focus of this review is to discuss relevant aspects of pericardial anatomy, and various methods of epicardial access.

Aims: Diagnosis of pericardial adhesions is challenging. Twisting of the left ventricle (LV) is essential for normal LV functioning. We experimentally characterized the impact of pericardial adhesions on epicardial and endocardial LV rotational mechanics with velocity vector imaging (VVI)., Methods and Results: In nine open-chest pigs, the heart was exposed while preserving the pericardium. Early-stage pericardial adhesions were simulated by instilling tissue glue to pericardial space. Using VVI, LV rotational mechanics was quantitatively assessed endocardially and epicardially along with haemodynamic data at baseline and following the experimental intervention. End-diastolic volume, ejection fraction, stroke volume, late diastolic filling velocity, and LV endocardial torsion decreased significantly. LV epicardial torsion showed only a trend towards decrease (P = 0.141). Endocardial twist and torsion decreased significantly (P = 0.007) from 8.6 +/- 2.2 degree and 1.497 +/- 0.397 degree/cm to 5.3 +/- 1.8 degree and 0.97 +/- 0.38 degree/cm, respectively; epicardial twist showed a trend towards a decrease in its magnitude. Gradients of endocardial/epicardial twist and torsion did not significantly change., Conclusion: The model suggests that early-stage pericardial adhesions reduce both epicardial and endocardial LV twist and torsion without a significant alteration in their transmural gradient. Selective endocardial/epicardial analysis of LV twisting mechanics may have a diagnostic role in detection of early formation of pericardial adhesions.

This study presents an animal model for the observation of adhesion formation, from a vascular viewpoint. In 60 Wistar rats, a 4 cm midline incision was made and a 0.5 cm square piece of silastic 0.2 mm thick was fixed on the right side of the peritoneum with two separate angular stitches of nylon 9/0. The rats were randomized in six groups of 10 animals and were operated on again on days 2, 4, 6, 8, 10 and 12 respectively. Biopsies for scanning electron microscopy were obtained by resecting a 2 x 2 cm square of parietal peritoneum around and covering the silastic patch. Foreign body reaction induced by the silastic patch and ischaemia caused by stitching are the stimuli for adhesion formation. The results showed a gradual progression in the type and tenacity of adhesion formation. The maximal degree of peritoneal reactive angiogenesis was noted between days 8 and 12, together with a decrease and a redistribution in the extent of adhesions. In the early stages, vascularization is part of the organization of adhesions while their extent is limited. Two parallel mechanisms take part in trauma healing: while omento-parietal adhesions are vascularized, new peritoneal tissue with its vascular network develops and covers the silastic surface and the traumatized area. This theory is supported by the presence of fibroblasts differentiating into mesothelial cells on day 8. Theoretically, a valid treatment in preventing adhesion formation should increase the peritoneal neoangiogenesis and the repair of peritoneal lesions, but at the same time prevent the vascularization of adhesions. The present model offers the possibility of testing the effect of any treatment or device for preventing post-operative adhesions in a relatively short time.

A prospective study was performed to determine whether a relationship exists between infertility as a result of pelvic adhesions, and raised follicle stimulating hormone (FSH). A total of 66 patients, who had a diagnostic laparoscopy and dye performed as part of their infertility work-up, had an early cycle serum FSH drawn one to two cycles after this procedure. Patients were divided into two groups, one with pelvic adhesions as a result of surgery, infection or endometriosis, and a control group consisting of those with a normal pelvis at laparoscopy or with minimal/mild endometriosis without adhesions. In the adhesion group, a correlation was noted between American Fertility Society (AFS) adhesion score and basal FSH concentration, although all FSH values for this group were within the normal range. This study suggests a correlation between pelvic adhesions and ovarian compromise, but a larger study involving more severe cases of adhesions is required to determine whether this finding is of clinical importance.