Pelvic Adhesion Formation Research Articles

Pelvic adhesion formation after intraperitoneal installation of gallstones in a rabbit model

Objective: To investigate whether intraperitoneal gallstones increase the risk of pelvic adhesions in a rabbit model. Design: Prospective, randomized, blinded, sham and human antigen controlled trial. Setting: An academic research environment. Subject(s): Twelve New Zealand white rabbits. Intervention(s): Twelve rabbits were divided into three groups of four each; a sham operation group, a gallstone and bile group (study group), and a human serum albumin and bile group (antigenic control). Three weeks after the operation individual subjects were randomized, with groups concealed to observers, and a necropsy was performed on each rabbit. Main Outcome Measurement(s): Necropsy was performed on each rabbit, and the adhesions were scored for extent, type, tenacity, inflammation, and gallstone involvement. Result(s): There was a statistically and biologically significant increase in gallstone involvement in adhesions, especially pelvic adhesions, in the study group. Conclusion(s): This study, along with an increasing number of case reports, suggests that gallstones inadvertently left in the peritoneal cavity may increase the morbidity of laparoscopic cholecystectomy. In females of reproductive age these gallstones may induce pelvic adhesions that may interfere with fertility or be associated with pelvic pain.

Barrier agents for preventing adhesions after surgery for subfertility.

Pelvic adhesions can be the result of inflamation, endometriosis or surgical trauma. Prevention of postoperative adhesions (either new or reoccurance) has been postulated by using barriers to prevent two surfaces being in contact. When pelvic surgery is being undertaken strategies to reduce pelvic adhesions occurring may be undertaken and these include barrier agents which are placed between the pelvic structures. Two synthetic barriers with differential characteristics are commercially available: oxidised regenerated cellulose (Interceed) and polytetrafluoroethylene (PTFC) (GoreTex). The objective of this review was to assess the effect of mechanical barriers (materials interposed between pelvic structures to prevent adherence of serosal surfaces) used during pelvic surgery in women of reproductive age on pregnancy rates, pelvic pain, or postoperative adhesion reformation. The Cochrane Menstrual Disorders and Subfertility Group specialised register of controlled clinical trials was undertaken. In addition, companies were contacted for unpublished trials. Randomised controlled trials or controlled clinical trials of barriers versus no treatment or other barriers in women undergoing fertility preserving pelvic surgery. Reviewers assessed eligibility and trial quality. 15 randomised controlled trials were included. Five trials randomised patients while the remainder randomised pelvic organs. Laparoscopy was the primary surgical technique in six trials while the remaining trials were laparotomy. Indications for surgery included myomectomy (five trials), ovarian surgery (four trials), pelvic adhesions (six trials), endometriosis (two trials) and mixed (one trial). Thirteen trials assessed Interceed versus no treatment, two assessed Interceed versus Gore-Tex, one trial assessed Gore-Tex versus no treatment, and one trial assessed Seprafilm versus no treatment. No study reported pregnancy or reduction in pain as an outcome. The use of Interceed in women was associated with reduced incidence of pelvic adhesion formation, both new formation and re-formation following laparoscopic surgery and after laparotomy. Gore-Tex was more effective than no barrier or Interceed in preventing adhesion formation. There was limited evidence that Seprafilm was effective in preventing adhesion formation in women following myomectomy. The absorbable adhesion barrier Interceed reduces the incidence of adhesion formation, both new formation and re-formation, at laparoscopy and laparotomy, but there are insufficient data to support its use to improve pregnancy rates. Gore-Tex may be superior to Interceed in preventing adhesion formation but its usefulness is limited by the need for suturing and later removal. There was no evidence of effectiveness of Seprafilm in preventing adhesion formation.

Pelvic Adhesions Contain Sex Steroid Receptors and Produce Angiogenesis Growth Factors

Objective: To evaluate female pelvic adhesion tissue for the presence of estrogen receptor (ER), progesterone receptor (PR), basic fibroblastic growth factor (basic-FGF), and vascular endothelial growth factor (VEGF). Design: Descriptive study. Setting: Patients at a tertiary medical center. Patients: Female reproductive age patients undergoing gynecologic surgery who were not receiving hormonal therapy. Interventions: Female reproductive tract peritoneal adhesion tissue was excised, frozen, and sent for immunohistologic evaluation. Main Outcome Measure: Presence of ER, PR, basic-FGF, and VEGF in adhesion tissue. Results: Nineteen of 19 specimens were positive for PR; 16 of 19 specimens were positive for ER, which was present in a variety of the different cell types constituting adhesion. Vascular endothelial growth factor and basic-FGF were detected in endothelial cells of blood vessels supplying this tissue as well as in mesothelial cells. Conclusion: Adhesion tissue contains ER, PR, and growth factors that may be important in the genesis of the permanent fibrovascular bands between pelvic organs. This supports the theoretical possibility of hormonal manipulation of these tissues to negatively influence postoperative pelvic adhesion formation.

Role of hypoestrogenism or sex steroid antagonism in adhesion formation after myometrial surgery in primates

To determine the contribution of estrogen in the development of pelvic adhesions during myometrial surgery. A randomized, prospective study in the nonhuman primate. A primate colony, Department of Obstetrics and Gynecology, Eastern Virginia Medical School. All primates were assigned prospectively to one of three treatment groups: [1] GnRH analogue (GnRH-a), [2] mifepristone, or [3] vehicle control. After 3 months of treatment, a standard uterine fundal hysterotomy, for full thickness endometrial biopsy, was performed at the time of exploratory laparotomy, with subsequent scoring of utero-omental adhesions to the hysterotomy site at a future staging procedure based upon adhesion area, vascularity, and tenacity. Serum was drawn on the day of surgery for E2 determination. Endometrial height, from the surface interface between the endometrium and myometrium, was used as a bioassay of estrogen activity. The hypoestrogenic (GnRH-a) group and the mifepristone group had significantly fewer utero-omental adhesions compared with the normally cycling control monkeys as measured by a lower adhesion score. Similarly, the endometrial thickness was significantly reduced in the GnRH-a and mifepristone groups (one-third) compared with the cycling controls, demonstrating the effects of either hypoestrogenism or noncompetitive estrogen antagonism. Serum E2 on the day of surgery was predictive of the postoperative adhesion score by both a regression analysis and analysis of covariance. The actions of E2 seem to have a dramatic effect on the formation of pelvic adhesions after myometrial surgery.

384 The role of local fibrinolytic activity of the rats uterine horns (UH) in pathogenesis of pelvic adhesion formation

384 The role of local fibrinolytic activity of the rats uterine horns (UH) in pathogenesis of pelvic adhesion formation

Pelvic Adhesion Formation after Pelvic Lymphadenectomy: Comparison between Transperitoneal Laparoscopy and Extraperitoneal Laparotomy in a Porcine Model

Compared to extraperitoneal laparotomy, the transperitoneal approach is associated with increased enteric morbidity. Recently, transperitoneal laparoscopy has been employed as a method to surgically stage patients with gynecologic malignancies. The objective of this study was to investigate pelvic adhesion formation in a porcine model after pelvic lymphadenectomy performed via transperitoneal laparoscopy (LS) compared to extraperitoneal laparotomy (EP). Ten adult, female hogs underwent LS and 10 underwent EP. A complete pelvic lymphadenectomy was performed in each animal. Three weeks after the lymphadenectomy, the animals underwent exploratory laparotomy, and the adhesions were quantified. Nineteen animals were evaluable. The adhesion scores for the laparoscopy group ( N = 10, mean = 0.075 ± 0.17) were not statistically different from those of the laparotomy group ( N = 9, mean = 0.28 ± 0.52, P > 0.5). Eight of 10 (80%) and 5 of 9 (56%) animals in the LS and EP groups, respectively, had no adhesions after pelvic lymphadenectomy. Adhesion formation is one of many critical issues concerning the utility of pretreatment surgical staging, especially for cancer of the cervix. It is remarkable that only 20% of the animals undergoing laparoscopy in this study had de novo adhesions after pelvic lymph node dissection and that the mean total adhesion score was not statistically different from the extraperitoneal laparotomy. Therefore, transperitoneal laparoscopic pelvic lymphadenectomy may not induce the degree of adhesion formation associated with the transperitoneal laparotomy technique.

Nonsteroidal antiinflammatory drugs and reproduction

The role of nonsteroidal antiinflammatory drugs in human reproduction and reproductive disorders is reviewed. Nonsteroidal antiinflammatory drugs inhibit the biosynthesis of prostanoids and can cross the placental barrier into the fetal circulation. Nonsteroidal antiinflammatory drugs are the treatment of choice in primary dysmenorrhea and intrauterine contraceptive device-induced dysmenorrhea and menorrhagia. Nonsteroidal antiinflammatory drugs can be used for effective control of menorrhagia, preterm labor, and polyhydramnios and for prevention of preeclampsia, but larger definitive clinical trials are needed. Prostaglandin inhibition with some nonsteroidal antiinflammatory drugs appear promising in the relief of some premenstrual symptoms and in the prevention of postoperative pelvic adhesion formation, but more studies are needed in women. Whereas implantation and tubal mobility are mediated by local prostaglandins, the potential use of nonsteroidal antiinflammatory drugs to suppress prostaglandin in these reproductive processes for enhancing or reducing fertility warrants further studies. In the last 2 decades nonsteroidal antiinflammatory drugs have been used increasingly in the treatment of some reproductive disorders and are promising for many others.

Effectiveness of Two Barriers at Inhibiting Post-radical Pelvic Surgery Adhesions

Objective: To compare the abilities of Gore-Tex Surgical Membrane (Gore-SM) and Interceed to inhibit post-radical pelvic surgery adhesion formation in a porcine model of radical hysterectomy, salpingo-oophorectomy, and resection of pelvic peritoneum. Methodology: Twenty-seven hogs were evaluated. After completion of the radical resection animals were randomized to no treatment or covering the peritoneal defect with a tailored sheet of Gore-SM or Interceed. The Gore-SM was secured in place using a continuous running 4-O Prolene suture while the Interceed was allowed to adhere without sutured attachment. Four weeks after the initial surgery, the animals were reexplored, adhesions quantified, and note was made of any segments of small bowel that were adherent into the pelvis. Results: One animal in each of the treatment groups died of respiratory compromise in the postoperational period. Adhesion scores for the Interceed covered pelvis (n = 9; mean = 0.04 ± 0.04) were significantly less than those treated with Gore-Sm (n = 9, mean = 0.18 ± 0.15, P = 0.02). Both treated groups had significantly fewer adhesions in the pelvis than did the controls (n = 7, mean 1.33 ± .51; vs Interceed P = 0.0005, vs Gore SM, P = 0.0007). Conclusions: Interceed was a more effective barrier for postoperative adhesion prophylaxis than the Gore-SM. Interceed also offered a technical advantage at time of placement.

Ketorolac Tromethamine, a Nonsteroidal Anti-inflammatory Drug: Ability to Inhibit Post-radical Pelvic Surgery Adhesions in a Porcine Model

The objective of this study was to investigate the ability of ketorolac tromethamine, a parenterally administered nonsteroidal anti-inflammatory drug (NSAID), to inhibit post-radical pelvic surgery adhesion formation (PRPSA). Twenty adult female hogs undergoing radical hysterectomy, bilateral salpingo-oophorectomy, and resection of pelvic peritoneum were used. Animals were randomized to either ketorolac (4 mg/kg loading dose 45 min prior to skin incision, followed by 2 mg/kg 1M every 8 hr for nine doses) or no adjuvant therapy. Four weeks after surgery, repeat celiotomy was performed, and adhesions were quantified. Note was made of any bowel segments adherent to the pelvis. Adhesion scores for the ketorolac-treated animals ( n = 9, mean = 0.92 ± 0.54, median = 0.90) were significantly less than those for control animals ( n = 10, mean = 6.73 ± 2.21, median = 7.03, P = 0.0001). Similarly, significantly fewer treateed animals had small bowel loops adherent in the pelvis when compared to control animals (11% vs 90%, P = 0.001). Ketorolac is an effective inhibitor of PRPSA formation and limits small bowel adherence to the pelvis.

The Gore-Tex Surgical Membrane: Effectiveness as a barrier to inhibit postradical pelvic surgery adhesions in a porcine model

Radical pelvic surgery has well-defined side effects, many of which may be related to the formation of pelvic adhesions. The effectiveness of different agents at limiting the formation of postradical pelvic surgery adhesions (PRPSA) has been variable to date. Use of a barrier could be beneficial not only by limiting adhesion formation but by acting as a “pelvic lid” to elevate the bowel out of a radiation treatment field and therefore limit subsequent radiation injury and associated fistula formation. We investigated the ability of the Gore-Tex Surgical Membrane (Gore-SM) to inhibit PRPSA in 20 adult female hogs undergoing radical hysterectomy, bilateral salpingo-oophorectomy, and resection of pelvic peritoneum. After completion of the radical resection, animals were randomized to either no attempt at covering the peritoneal defect or covering it and a 1-cm margin of intact peritoneum with a tailored sheet of Gore-SM. The membrane was secured in place using a continuous running 4-O Prolene suture around the perimeter. No intraoperative deaths occurred. No animal evidenced signs of bleeding, infection, bowel obstruction, or abscess formation. Four weeks after the initial surgery, the animals were again anesthetized, exploratory celiotomy was performed, and adhesions were quantified with specific note being made of any segments of small bowel that were adherent into the pelvis. Animals were then sacrificed. Adhesion scores for the Gore-SM-treated animals ( n = 10; mean, 0.14 ± 0.12; median, 0.21) were significantly less than those of animals with the noncovered pelvis ( n = 10; mean, 1.33 ± 0.41; median, 1.42; P < 0.001). Similarly, significantly fewer animals treated with Gore-SM had small bowel loops adherent in the pelvis when compared to control animals (10% vs 70%; P < 0.01). In this model, meticulously suturing the membrane in place with continuous permanent suture, the Gore-SM was an effective barrier for postoperative adhesion prophylaxis and successfully limited small bowel adherence into the pelvis.

Inability of polyglycolic acid mesh to inhibit immediate post-radical pelvic surgery adhesions

The ability of a polyglycolic acid (PGA)-derived mesh to limit the formation of immediate postoperative pelvic adhesions after radical resection of the pelvic viscera and peritoneum was investigated. Twenty female canines underwent total abdominal hysterectomy, bilateral salpingo-oophorectomy, and infracolonic omentectomy. The entire peritoneum of the pelvis and lower abdomen also was removed. In ten animals, a single layer of PGA mesh, tailored to cover the deperitonealized area, was sutured in place. Reperitonealization was not performed in control animals. Four weeks after initial surgery, animals were reexplored and killed. Adhesions to the anterior abdominal wall and pelvis were quantified and graded: n Anterior abdominal wall Pelvis Abscesses Mesh 10 2.93 ± 1.50 15.13 ± 15.19 4 Control 10 0.18 ± 0.26 ( P < 0.05) 2.43 ± 1.60 0 ( P < 0.05) ( P < 0.05) These data indicate that the placement of a PGA mesh induces significant pelvic adhesions and potentiates the formation of pelvic abscesses.

An appraisal of barrier agents in the reduction of adhesion formation following surgery.

Reduction of pelvic adhesion formation and reformation represents a major challenge for the reproductive pelvic surgeon. Recently developed barrier methods appear promising, offering the advantage of nonsystemic therapy. Presented is a review of the literature and appraisal of the evolution of barrier agents. The current state-of-the-art barrier agent Interceed (TC-7) is discussed.

8 Laparoscopic treatment of ectopic pregnancy

Over the last decade and a half the success and safety of endoscopic surgery for ectopic pregnancy has been established. Shapiro and Adler (1973) reported laparoscopic salpingectomy using electrocoagulation followed by excision. Soderstrom (1981) followed with the snare technique of salpingectomy. Valle and Lifchez (1983) reported tubal patency rates approaching and attaining 100% following salpingostomy in the sole oviduct during laparotomy encouraged continued laparoscopic approach. DeCherney (1981) described linear salpingostomy via a cutting current in 18 women with an intrauterine pregnancy rate of 50% 1 year afterwards. No spontaneous abortions or repeat ectopics were reported. Pouly et al (1986) described laparoscopic salpingostomy in 321 women with a resultant 64% intrauterine pregnancy and 22% repeat ectopic rate. These studies support the realization that previous surgical approaches per laparotomy for ectopic pregnancy may be achieved endoscopically, but intraoperative and postoperative complications have occurred. As noted by Kelly et al (1979) and Richards (1984) these consist mainly of persistent or delayed haemorrhage along with continued trophoblastic growth. Haemorrhage is most often a result of failed salpingostomy in larger ectopics. Continued trophoblastic development requiring repeat surgical exploration due to incomplete removal of tissue has been reported by Pouly (1986) in as many as 5% of cases. This rare but reported consequence signals the importance of following quantitative HCG concentrations into the negative range. Occasionally HCG levels remain elevated more than 30 days postoperatively with eventual resolution; Cartwright et al (1986) claim that tubal patency rates appear to be unaffected by this prolonged clearance of tissue. Despite infrequent morbidity, laparoscopic treatment of ectopic pregnancy, in comparison to laparotomy, significantly shortens hospital stays, operating time, convalescence and postoperative analgesic requirements (Brumsted et al, 1988). Endoscopic surgery also reduces postoperative formation of pelvic adhesions (Fayez and Schneider, 1987). As familiarity and technical expertise with endoscopy continues to increase, exploratory laparotomy may be considered too radical an approach to ectopic pregnancy treatment regardless of the procedure performed.

Use of Pentoxifylline as an Adjuvant to Reduce Primary Postsurgical Adhesion Formation: Preliminary Investigations in a Rodent Model

Formation of pelvic adhesions following infertility procedures remains a significant problem in reproductive surgery. Pentoxifylline, a methylxanthine derivative, is known to decrease leukocyte activation, ameliorate phagocytic injury, and enhance plasminogen activator production. To determine whether these properties of pentoxifylline might protect mesothelial surfaces from perioperative damage and hence prevent adhesion formation, we evaluated the effect of pentoxifylline on peritoneal healing in a hamster model for primary pelvic injury. Perioperative pentoxifylline therapy significantly reduced posttraumatic adhesion formation as compared to vehicle-treated controls. Dose–response studies demonstrate maximal adhesion prevention with doses ranging from 0.1 to 10 mg/kg/12 hours given subcutaneously over the course of 3 days. Intraperitoneal administration did not convey additional benefit. Delaying the onset of pentoxifylline administration by as much as 72 hours did not significantly impair adhesion reduction. These data demonstrate pentoxifylline to be a potent positive modulator of peritoneal healing following pelvic trauma. Further studies to characterize the potential application of pentoxifylline as an adjuvant in reproductive surgery are indicated. (J GYNECOL SURG 5:367, 1989)

Prevention of pelvic adhesion formation by different modalities of treatment : Fayez JA; Schneider PJ Section on Reproductive Endocrinology, Department of Obstetrics and Gynecology, Bowman Gray School of Medicine, Winston-Salem, NC 27103, USA Am. J. Obstet. Gynecol.; 157/5 (1184–1188)/1987/

Prevention of pelvic adhesion formation by different modalities of treatment : Fayez JA; Schneider PJ Section on Reproductive Endocrinology, Department of Obstetrics and Gynecology, Bowman Gray School of Medicine, Winston-Salem, NC 27103, USA Am. J. Obstet. Gynecol.; 157/5 (1184–1188)/1987/

Prevention of Pelvic adhesion formation by different modalities of treatment

This prospective study was designed to investigate the effect of glucocorticoids, promethazine (Phenergan), hyskon, heparin, and Ringer's lactated solution in the prevention of pelvic adhesion formation after pelvic surgery. The patients were divided into two groups: The first consisted of 396 patients who had laparotomy for different types of pelvic surgery, and the second group consisted of 546 patients who had operative laparoscopy for different types of pelvic disease. Patients in these two major groups were divided prospectively into different subgroups with different modalities of adjuvant therapy to prevent postoperative pelvic adhesions. A second-look laparoscopy was performed for some of the patients who failed to conceive in each of these subgroups. Pregnancy rate and adhesion formation were compared between these subgroups with no statistical difference noted. It is concluded that glucocorticoids, promethazine, heparin, and hyskon have no therapeutic advantage over Ringer's lactated solution in the prevention of postoperative pelvic adhesion formation.

Effects of dexamethasone on proliferation of autologous fibroblasts and on the immune profile in women undergoing pelvic surgery for infertility

Dexamethasone (DEX) was administered postoperatively to six patients undergoing lysis of pelvic adhesions. During therapy the proportion of T cells among the peripheral blood lymphocytes sharply declined from 60% to 20%. Response to T- and B-cell mitogens decreased to 20% to 40% of the original response prior to surgery. DEX-containing serum had an enhancing effect on the growth of autologous fibroblasts derived from pelvic adhesions (50% more than the effect of pretreatment serum). Pure cortisol and DEX induced a similar enhanced growth. The enhancing ability of the patients' sera disappeared 48 hours after discontinuation of DEX, corresponding to the recovery of the lymphoid system. If there is any benefit in steroid treatment to prevent pelvic adhesion formation, it is apparently not via an inhibitory effect on fibroblast proliferation. Such treatment, however, clearly suppresses the immune response of the patients during the early postoperative course.

CAUSES OF FAILURE OF RECONSTRUCTIVE INFERTILITY MICROSURGERY

Several factors affect the result of reconstructive fertility surgery and may be responsible for failure. A major factor in failure has been the postoperative reformation of pelvic adhesions or their occurrence de novo. In the effort to diminish postoperative adhesions many agents have been tried parenterally and intraperitoneally. Clinical observations in the human which have been confirmed by animal experimentation indicate that the most effective way to prevent adhesions is to minimize tissue trauma and prevent tissue dessication. Failure may be associated with the reocclusion of the oviducts or the formation of extensive periadnexal and pelvic adhesions that inhibit ovum pickup by the fimbriae. Reocclusion of the oviduct within the 1st few months after tubotubal anastomosis is usually because of a poor technique -- faulty anastomosis or failure to excise all the pathology. In cases of infertility associated with endometriosis failure to excise all the lesions may be the cause of failure. Attention is directed to the following factors affecting the result of reconstructive fertility surgery: preexisting epithelial pathology; intratubal adhesions; progressive inflammatory disease; shortened fallopian tube; disturbances in tuboovarian spatial relationships; and incidental postopertive pelvic inflammatory disease. Morphologic restoration of the pelvis and reestablishment of tubal patency do not always mean restoration of function. Improved understanding of tubal physiology and the factors involved in the successful fusion and segmentation of the gametes and significant improvements in reconstructive surgical techniques may work to substantially improve the results of reconstructive surgery in the future.

Role of Dextran 70 in Microtubal Surgery

Pelvic adhesion formation represents a major problem following fallopian tube surgery for infertility. Intraperitoneal dextran may prevent pelvic adhesions. Extensive personal clinical experience (W. H. U.) with intraperitoneal dextran organ-flotation on completion of tubal and ovarian surgery has appeared to limit adhesions. A specific study was designed to test the validity of this theory. Four randomized groups of rabbits were subjected to bilateral tubocornual division and microsurgical reanastomosis with total hemostasis and pelvic lavage. Routine peritoneal closure was performed on one group, but followed instillation of 30 to 50 ml of normal saline into the peritoneal cavities of the second group, and 30 to 50 ml of 6% dextran 70 into those of the third. Study of fourth group, which received 32% dextran 70 in the peritoneal cavity, was discontinued because of complications. A second laparotomy was performed 4 weeks later for precise assessment and photography of adhesion formation. Each animal was mated 4 weeks after the second operation in order to determine fertility rates. Reduced adhesion formation and increased fertility rates following the instillation of dextran are reported. A role for dextran 70 in infertility surgery is recommended.