Steven Fox
December 7, 2011 — A majority of intrauterine devices (IUDs) that cause uterine perforations may be safely removed with laparoscopy, rather than resorting to more invasive surgery, according to researchers who reviewed nearly 40 years of research on the topic.
On the basis of their review, Richdeep Gill, MD, from the Department of Surgery, University of Alberta, Edmonton, Canada, and colleagues suggest that the laparoscopic approach be first-line therapy in patients who present with symptoms, and that it be considered a reasonable option in patients without symptoms.
Their article appears in the January 2012 issue of Contraception .
"Uterine perforation by [IUDs] is a rare but well recognized complication," they write. However, "[o]ur review demonstrates that a majority of IUD perforations may be amenable to laparoscopic retrieval." Furthermore, they say, the location of the perforated IUD within the abdomen does not appear to be a major factor in outcomes.
According to some estimates, anywhere from 0 to 1.3 per 1000 women implanted with the devices will experience uterine perforation.
In the past, patients who presented with adhesions and perforated viscera often required laparotomy to remove their IUDs, but in recent years improvements in laparoscopic technique and technology have allowed surgeons to use the less-invasive approach to achieve the same results, the authors say.
To find out more about how advances in laparoscopic surgery have affected the management of patients with perforated IUDs, the authors conducted a systematic search of the literature from 1970 through 2009, using MEDLINE/PubMed, Embase, Cochrane Library, and OCLC PapersFirst.
The authors identified 179 cases in which surgeons attempted to use laparoscopy to remove perforated IUDs. Mean age of the patients was 26 years, with an age range from 17 to 49 years. More than three-quarters of the women had previously given birth at least twice.
The patients presented with various symptoms, the most common being pain and unexpected pregnancy, the authors say. All participants initially underwent diagnostic laparoscopy.
The authors report that this initial laparoscopy was successful in all 179 cases. Surgeons subsequently used laparoscopy to successfully remove the perforated IUDs in 64.2% (115/179) of cases.
Laparotomy was done in 34.6% (62/179) of cases, either after diagnostic laparoscopy or after laparoscopic removal had been attempted.
The presence of adhesions appeared to be a factor in unsuccessful outcomes with laparoscopy. Among women who required laparotomy to remove their IUDs, 75% (15/20) reported the presence of adhesions.
In contrast, women whose IUDs were successfully removed by laparoscopy reported a 37.7% (20/53) incidence of adhesions.
Perforated IUDs were found in a variety of locations, including the omentum (26.7%), pouch of Douglas (21.5%), colonic lumen secondary to perforation (10.4%), myometrium (7.4%), broad ligament (6.7%), free within the abdomen (5.2%), small bowel serosa (4.4%), colonic serosa (3.7%), and mesentery (3%). The remaining 11% were found in rare locations, including the bladder, appendix, abdominal wall, fallopian tube, ovary, retroperitoneum, and small bowel. The location appeared to have little effect on the outcomes, the reviewers say.
They conclude: "[T]his systematic review highlights how advances in laparoscopic technique and skill have allowed surgeons to safely retrieve IUDs without laparotomy. We recommend an attempt at laparoscopic removal as first-line treatment in symptomatic patients and as a reasonable treatment option in asymptomatic patients."
The authors have disclosed no relevant financial relationships.
Contraception. 2012;85:15-18. Abstract
Thursday, December 08, 2011
Sunday, December 04, 2011
Testimony on the Resorbable Adhesion Barrier REPEL-CV
September 19, 2007
Testimony of Peter Lurie, M.D., M.P.H., and Eunice Yu
Public Citizen’s Health Research Group
Public Citizen’s Health Research Group opposes the approval of REPEL-CV, a resorbable polymer adhesion barrier, for the proposed indication of reduction in surgical adhesions. Minimum criteria for the approval of an adhesion barrier should be the demonstration of a clinically significant improvement and a reasonable assurance of safety. Neither is present in this case.
Background
Opening the sternum (sternotomy) during cardiac surgery can result in the formation of dense scar tissue called adhesions between the outside of the heart (epicardium) and the inner portion of the chest wall. REPEL-CV is implanted between the epicardium and the chest wall and, in theory, resorbed within 28 days. During this period, it is supposed to reduce the incidence and severity of adhesions, making subsequent surgery less difficult. It is noteworthy that the sole proposed indication (“reducing the incidence, severity and extent of post-operative adhesion formation in patients undergoing cardiac surgery via sternotomy”[1]) makes no claim of any clinical benefit to the patient.
In its pre-market application (PMA) for REPEL-CV, SyntheMed Inc. submitted a single randomized, evaluator-blinded pivotal trial of 142 pediatric patients (73 treatment, 69 control) who were expected to require at least two sternotomy procedures for repair of congenital heart malformations. The device was implanted in the first surgery and adhesions were measured in the second. In the treatment group, REPEL-CV was sutured to the margins of the open pericardium (a sac surrounding the heart) below the sternum in the first operation, while in the control group the pericardium was left open. Following various patient withdrawals and discontinuations, the trial yielded an intent-to-treat population of 56 patients in the treatment arm and 54 in the control arm, all of whom underwent the second procedure. Most study endpoints were based upon the following four-point scale developed in the feasibility trials.
Grade 0 = No adhesions
Grade 1 = Mild adhesions (filmy, non-cohesive adhesions requiring blunt dissection to separate the space between the epicardium and sternum)
Grade 2 = Moderate adhesions (filmy, non-cohesive adhesions requiring a combination of blunt and selective sharp dissection to separate the space between the epicardium and the sternum)
Grade 3 = Severe adhesions (dense, cohesive adhesions requiring extensive sharp dissection to separate the space between the epicardium and the sternum)[2]
The primary endpoint was the percentage of the surgical site with Grade 3 adhesions detected during the second surgery. Three of the four secondary endpoints also drew from this scale by measuring the prevalence of Grade 0-2 adhesions, or by characterizing the patients by their most severe adhesion grade. The final secondary endpoint measured the time required to dissect adhesions at the second sternotomy.
Efficacy
REPEL-CV Does Not Reduce the Incidence of Adhesions
The trial showed a significant reduction in the prevalence at second sternotomy of Grade 3 adhesions in patients with the REPEL-CV implant (21.3%) compared with those whose pericardiums were left open (47.3%; p=0.0008).[3] However, the product failed to actually prevent adhesions overall, whether measured by the percentage of the operative surface area with Grade 0 adhesions (mean 2.9% vs. 0.9%; p=0.32)[4] or by the percentage of patients who were completely adhesion-free (1.8% vs. 0%).[5] The product did seem to reduce the severity of adhesions. For the primary efficacy variable, there was an overall redistribution from Grade 3 adhesions into Grade 2 and Grade 1 adhesions.[6] The percentage of patients characterized by their worst adhesion showed a similar trend: REPEL-CV resulted in a “one-grade shift downwards,”[7] from Grade 3 into Grade 2. This is very different from “reducing the incidence” of adhesions, part of the indication sought by the company.
Lack of Clinical Endpoints
The above adhesion scale has never been validated with clinical outcomes such as mortality, infection, or complications of adhesions. Indeed, we are aware of no circumstance in which it has been used except for in the development of REPEL-CV. One observer suggests that pericardial adhesions “may be beneficial” for patients because adhesions prevent “excessive movement of the heart devoid of its normal pericardial support.”[8] Lack of clarity over the significance of adhesions makes the demonstration of an actual clinical benefit all the more important.
Given that the apparent purpose of adhesion prevention is the facilitation of follow-up surgeries, the only (secondary) endpoint with a resemblance to clinical significance is adhesion dissection time. Yet this endpoint was not influenced by REPEL-CV (25.9 minutes for the treatment group vs. 25.0 minutes for the control group; p=0.84).[9] The lack of a positive result for the only clinical endpoint calls into question the usefulness of the device.
The major limitations of using adhesions as the primary outcome are underscored by the history of FDA’s guidance on clinical trials for resorbable adhesion barrier devices. In its original 1999 Draft Guidance for such devices in abdominal and/or pelvic surgery, the agency made clear the importance of clinical endpoints: “Optimally, endpoints should directly address clinical outcome measures … The most direct method of providing valid scientific evidence of effectiveness is to select an appropriate clinical endpoint(s) and design a study that may demonstrate a statistically significant and clinically meaningful effect on recognized adhesion-related morbidity.”[10] After discussing particular endpoints for abdominal and pelvic surgery and acknowledging possible impediments to the use of clinical endpoints, the section concludes, “sponsors are encouraged to directly assess clinical endpoints whenever possible.”
This did not sit well with the Adhesion Barrier Task Force, which represented the manufacturers of adhesion barriers including SyntheMed’s predecessor company, Life Medical Sciences. In comments on the Draft Guidance submitted to the FDA, the Task Force declared that, “Until there is more information and standards established for conducting these studies with highly specific clinical endpoints, it would be overly burdensome to suggest that measuring specific clinical outcomes might be the means of assessing product effectiveness as this has never been accomplished to date.”[11]
The objections evidently had the desired effect. In the final Guidance, after stating that clinical outcomes are “the most direct method of providing valid scientific evidence of effectiveness,” the FDA concludes, “The clinical outcomes associated with adhesions may be reasonably assessed by parameters which are more immediately measurable and potentially less confounded.”[12] At least three of five examples of appropriate outcomes given in the final Guidance mention only adhesions; the other two are unclear.
Inadequate Blinding
While the study design rightly emphasized blinding of the evaluating surgeon at second sternotomy, this design was undermined. Although REPEL-CV should be resorbed within 28 days, “implanted test material or a fibrous capsule, or other abnormal tissue”[13] was observed in 30.4% of patients in the REPEL-CV group and 1.9% of patients in the control group at second sternotomy (p<0.0001). Finding this material during the second sternotomy would likely unblind the evaluator, potentially leading to downgrading of adhesion severity in the REPEL-CV group.
Safety
In addition to these efficacy concerns, there were troubling signs of possible dangers associated with the device. There were trends toward higher risk of death (16.4% vs. 13.0%), mediastinial infection (5.5% vs. 1.4%, or 4 vs. 1 patient), and adverse events possibly, probably or definitely related to the study (8.2% vs. 1.4%).[14] These trends were not statistically significant, but with a total population of 142 patients who underwent the first sternotomy, the study was only, by the sponsor’s own admission, “adequate to rule out a 18% disadvantage (15% [mortality rate in the control group] vs. 33% [mortality rate in the treatment group], 2.8 odds ratio) with 80% power and one-sided 5% Type I error.”[15] Thus, REPEL-CV-treated patients would have had to have died at almost three times the control rate for this study to have reached statistical significance. The consistent direction of the adverse effects observed, even if non-significant, is concerning.
Parallels with Intergel
The data on REPEL-CV bring to mind the case of Intergel, a product made from sodium hyaluronate and intended to reduce pelvic adhesions. In that case, adhesions were also shown to be reduced by the product. However, despite the use of an adhesion scale with arguably more validation than that used in the REPEL-CV study, FDA was concerned that, “There is little experience in the clinical literature correlating the [Modified American Fertility Society] score with clinical outcomes.”[16] The pivotal Intergel trial demonstrated, as here, a consistent but non-statistically significant increase in infection rates. Initially, the FDA rejected the sponsor’s application, but the company appealed to an external Dispute Resolution Panel, which recommended approval. The FDA then reversed itself and approved the device. On April 16, 2003, less than two years after the device was approved, the company removed the device from the market due to dozens of reports of post-operative pain requiring repeat surgery, foreign body reactions and tissue adherence, including three deaths.[17] This history should give one pause before approving an adhesion barrier with only surrogate endpoints and a questionable safety record.
Conclusion
SyntheMed has simply failed to demonstrate that its product will have any important impact upon the public health. To do so, the following conditions would have to be met:
1.The patients receiving the device would have to undergo resternotomy; in fact, only a minority of patients will undergo resternotomy and all implanted patients face the potential dangers of the device.
2.The product would have to reduce adhesions; in fact, the product reduces the severity but not the incidence of adhesions.
3.The adhesions would have to have clear clinical significance; in fact, their significance remains unclear and the product had no impact upon the only clinical outcome.
4.The product would have to have an appropriate safety profile; in fact, there are trends in the direction of increased infection and even increased mortality.
For these reasons, Public Citizen’s Health Research Group opposes the approval of this device.
--------------------------------------------------------------------------------
[1] SyntheMed. Proposed Package Insert for REPEL-CV. September 17th, 2007, p. 3.
[2] SyntheMed. REPEL-CV P07005: Summary of Safety and Effectiveness. September 17th, 2007, p. 34.
[3] SyntheMed. REPEL-CV P07005: Summary of Safety and Effectiveness. September 17th, 2007, Table 17.
[4] ibid.
[5] ibid., Table 18.
[6] ibid., Table 17.
[7] ibid., p. 53.
[8] Nkere UU. Postoperative adhesion formation and the use of adhesion preventing techniques in cardiac and general surgery. ASAIO Journal 2000;46:654-6.
[9] SyntheMed. REPEL-CV P07005: Summary of Safety and Effectiveness. September 17th, 2007, p. 40.
[10] Center for Devices and Radiological Health. Guidance for Resorbable Adhesion Barrier Devices for Use in Abdominal and/or Pelvic Surgery; Draft Guidance. Food and Drug Administration, December 16, 1999.
[11] Burns JW. Letter to Dockets Management Branch (Docket 99D-5199). Adhesion Barrier Task Force, March 13, 2000.
[12] Center for Devices and Radiological Health. Guidance for Resorbable Adhesion Barrier Devices for Use in Abdominal and/or Pelvic Surgery; Guidance for Industry. Food and Drug Administration, June 18, 2002.
[13] SyntheMed. REPEL-CV P07005: Summary of Safety and Effectiveness. September 17th, 2007, p. 51.
[14] ibid., Table 21.
[15] ibid., p. 47.
[16] Richter KC. Letter to Lifecore Biomedical, Inc. Office of Device Evaluation, Center for Devices and Radiological Health, November 15, 2000.
[17] Sullivan MG. Intergel sales halted pending investigation of deaths, pain. Ob/Gyn News, May 15, 2003.
http://www.citizen.org/Page.aspx?pid=731
Testimony of Peter Lurie, M.D., M.P.H., and Eunice Yu
Public Citizen’s Health Research Group
Public Citizen’s Health Research Group opposes the approval of REPEL-CV, a resorbable polymer adhesion barrier, for the proposed indication of reduction in surgical adhesions. Minimum criteria for the approval of an adhesion barrier should be the demonstration of a clinically significant improvement and a reasonable assurance of safety. Neither is present in this case.
Background
Opening the sternum (sternotomy) during cardiac surgery can result in the formation of dense scar tissue called adhesions between the outside of the heart (epicardium) and the inner portion of the chest wall. REPEL-CV is implanted between the epicardium and the chest wall and, in theory, resorbed within 28 days. During this period, it is supposed to reduce the incidence and severity of adhesions, making subsequent surgery less difficult. It is noteworthy that the sole proposed indication (“reducing the incidence, severity and extent of post-operative adhesion formation in patients undergoing cardiac surgery via sternotomy”[1]) makes no claim of any clinical benefit to the patient.
In its pre-market application (PMA) for REPEL-CV, SyntheMed Inc. submitted a single randomized, evaluator-blinded pivotal trial of 142 pediatric patients (73 treatment, 69 control) who were expected to require at least two sternotomy procedures for repair of congenital heart malformations. The device was implanted in the first surgery and adhesions were measured in the second. In the treatment group, REPEL-CV was sutured to the margins of the open pericardium (a sac surrounding the heart) below the sternum in the first operation, while in the control group the pericardium was left open. Following various patient withdrawals and discontinuations, the trial yielded an intent-to-treat population of 56 patients in the treatment arm and 54 in the control arm, all of whom underwent the second procedure. Most study endpoints were based upon the following four-point scale developed in the feasibility trials.
Grade 0 = No adhesions
Grade 1 = Mild adhesions (filmy, non-cohesive adhesions requiring blunt dissection to separate the space between the epicardium and sternum)
Grade 2 = Moderate adhesions (filmy, non-cohesive adhesions requiring a combination of blunt and selective sharp dissection to separate the space between the epicardium and the sternum)
Grade 3 = Severe adhesions (dense, cohesive adhesions requiring extensive sharp dissection to separate the space between the epicardium and the sternum)[2]
The primary endpoint was the percentage of the surgical site with Grade 3 adhesions detected during the second surgery. Three of the four secondary endpoints also drew from this scale by measuring the prevalence of Grade 0-2 adhesions, or by characterizing the patients by their most severe adhesion grade. The final secondary endpoint measured the time required to dissect adhesions at the second sternotomy.
Efficacy
REPEL-CV Does Not Reduce the Incidence of Adhesions
The trial showed a significant reduction in the prevalence at second sternotomy of Grade 3 adhesions in patients with the REPEL-CV implant (21.3%) compared with those whose pericardiums were left open (47.3%; p=0.0008).[3] However, the product failed to actually prevent adhesions overall, whether measured by the percentage of the operative surface area with Grade 0 adhesions (mean 2.9% vs. 0.9%; p=0.32)[4] or by the percentage of patients who were completely adhesion-free (1.8% vs. 0%).[5] The product did seem to reduce the severity of adhesions. For the primary efficacy variable, there was an overall redistribution from Grade 3 adhesions into Grade 2 and Grade 1 adhesions.[6] The percentage of patients characterized by their worst adhesion showed a similar trend: REPEL-CV resulted in a “one-grade shift downwards,”[7] from Grade 3 into Grade 2. This is very different from “reducing the incidence” of adhesions, part of the indication sought by the company.
Lack of Clinical Endpoints
The above adhesion scale has never been validated with clinical outcomes such as mortality, infection, or complications of adhesions. Indeed, we are aware of no circumstance in which it has been used except for in the development of REPEL-CV. One observer suggests that pericardial adhesions “may be beneficial” for patients because adhesions prevent “excessive movement of the heart devoid of its normal pericardial support.”[8] Lack of clarity over the significance of adhesions makes the demonstration of an actual clinical benefit all the more important.
Given that the apparent purpose of adhesion prevention is the facilitation of follow-up surgeries, the only (secondary) endpoint with a resemblance to clinical significance is adhesion dissection time. Yet this endpoint was not influenced by REPEL-CV (25.9 minutes for the treatment group vs. 25.0 minutes for the control group; p=0.84).[9] The lack of a positive result for the only clinical endpoint calls into question the usefulness of the device.
The major limitations of using adhesions as the primary outcome are underscored by the history of FDA’s guidance on clinical trials for resorbable adhesion barrier devices. In its original 1999 Draft Guidance for such devices in abdominal and/or pelvic surgery, the agency made clear the importance of clinical endpoints: “Optimally, endpoints should directly address clinical outcome measures … The most direct method of providing valid scientific evidence of effectiveness is to select an appropriate clinical endpoint(s) and design a study that may demonstrate a statistically significant and clinically meaningful effect on recognized adhesion-related morbidity.”[10] After discussing particular endpoints for abdominal and pelvic surgery and acknowledging possible impediments to the use of clinical endpoints, the section concludes, “sponsors are encouraged to directly assess clinical endpoints whenever possible.”
This did not sit well with the Adhesion Barrier Task Force, which represented the manufacturers of adhesion barriers including SyntheMed’s predecessor company, Life Medical Sciences. In comments on the Draft Guidance submitted to the FDA, the Task Force declared that, “Until there is more information and standards established for conducting these studies with highly specific clinical endpoints, it would be overly burdensome to suggest that measuring specific clinical outcomes might be the means of assessing product effectiveness as this has never been accomplished to date.”[11]
The objections evidently had the desired effect. In the final Guidance, after stating that clinical outcomes are “the most direct method of providing valid scientific evidence of effectiveness,” the FDA concludes, “The clinical outcomes associated with adhesions may be reasonably assessed by parameters which are more immediately measurable and potentially less confounded.”[12] At least three of five examples of appropriate outcomes given in the final Guidance mention only adhesions; the other two are unclear.
Inadequate Blinding
While the study design rightly emphasized blinding of the evaluating surgeon at second sternotomy, this design was undermined. Although REPEL-CV should be resorbed within 28 days, “implanted test material or a fibrous capsule, or other abnormal tissue”[13] was observed in 30.4% of patients in the REPEL-CV group and 1.9% of patients in the control group at second sternotomy (p<0.0001). Finding this material during the second sternotomy would likely unblind the evaluator, potentially leading to downgrading of adhesion severity in the REPEL-CV group.
Safety
In addition to these efficacy concerns, there were troubling signs of possible dangers associated with the device. There were trends toward higher risk of death (16.4% vs. 13.0%), mediastinial infection (5.5% vs. 1.4%, or 4 vs. 1 patient), and adverse events possibly, probably or definitely related to the study (8.2% vs. 1.4%).[14] These trends were not statistically significant, but with a total population of 142 patients who underwent the first sternotomy, the study was only, by the sponsor’s own admission, “adequate to rule out a 18% disadvantage (15% [mortality rate in the control group] vs. 33% [mortality rate in the treatment group], 2.8 odds ratio) with 80% power and one-sided 5% Type I error.”[15] Thus, REPEL-CV-treated patients would have had to have died at almost three times the control rate for this study to have reached statistical significance. The consistent direction of the adverse effects observed, even if non-significant, is concerning.
Parallels with Intergel
The data on REPEL-CV bring to mind the case of Intergel, a product made from sodium hyaluronate and intended to reduce pelvic adhesions. In that case, adhesions were also shown to be reduced by the product. However, despite the use of an adhesion scale with arguably more validation than that used in the REPEL-CV study, FDA was concerned that, “There is little experience in the clinical literature correlating the [Modified American Fertility Society] score with clinical outcomes.”[16] The pivotal Intergel trial demonstrated, as here, a consistent but non-statistically significant increase in infection rates. Initially, the FDA rejected the sponsor’s application, but the company appealed to an external Dispute Resolution Panel, which recommended approval. The FDA then reversed itself and approved the device. On April 16, 2003, less than two years after the device was approved, the company removed the device from the market due to dozens of reports of post-operative pain requiring repeat surgery, foreign body reactions and tissue adherence, including three deaths.[17] This history should give one pause before approving an adhesion barrier with only surrogate endpoints and a questionable safety record.
Conclusion
SyntheMed has simply failed to demonstrate that its product will have any important impact upon the public health. To do so, the following conditions would have to be met:
1.The patients receiving the device would have to undergo resternotomy; in fact, only a minority of patients will undergo resternotomy and all implanted patients face the potential dangers of the device.
2.The product would have to reduce adhesions; in fact, the product reduces the severity but not the incidence of adhesions.
3.The adhesions would have to have clear clinical significance; in fact, their significance remains unclear and the product had no impact upon the only clinical outcome.
4.The product would have to have an appropriate safety profile; in fact, there are trends in the direction of increased infection and even increased mortality.
For these reasons, Public Citizen’s Health Research Group opposes the approval of this device.
--------------------------------------------------------------------------------
[1] SyntheMed. Proposed Package Insert for REPEL-CV. September 17th, 2007, p. 3.
[2] SyntheMed. REPEL-CV P07005: Summary of Safety and Effectiveness. September 17th, 2007, p. 34.
[3] SyntheMed. REPEL-CV P07005: Summary of Safety and Effectiveness. September 17th, 2007, Table 17.
[4] ibid.
[5] ibid., Table 18.
[6] ibid., Table 17.
[7] ibid., p. 53.
[8] Nkere UU. Postoperative adhesion formation and the use of adhesion preventing techniques in cardiac and general surgery. ASAIO Journal 2000;46:654-6.
[9] SyntheMed. REPEL-CV P07005: Summary of Safety and Effectiveness. September 17th, 2007, p. 40.
[10] Center for Devices and Radiological Health. Guidance for Resorbable Adhesion Barrier Devices for Use in Abdominal and/or Pelvic Surgery; Draft Guidance. Food and Drug Administration, December 16, 1999.
[11] Burns JW. Letter to Dockets Management Branch (Docket 99D-5199). Adhesion Barrier Task Force, March 13, 2000.
[12] Center for Devices and Radiological Health. Guidance for Resorbable Adhesion Barrier Devices for Use in Abdominal and/or Pelvic Surgery; Guidance for Industry. Food and Drug Administration, June 18, 2002.
[13] SyntheMed. REPEL-CV P07005: Summary of Safety and Effectiveness. September 17th, 2007, p. 51.
[14] ibid., Table 21.
[15] ibid., p. 47.
[16] Richter KC. Letter to Lifecore Biomedical, Inc. Office of Device Evaluation, Center for Devices and Radiological Health, November 15, 2000.
[17] Sullivan MG. Intergel sales halted pending investigation of deaths, pain. Ob/Gyn News, May 15, 2003.
http://www.citizen.org/Page.aspx?pid=731
Saturday, December 03, 2011
Adhesion prevention in gynaecological surgery.
J Obstet Gynaecol Can. 2010 Jun;32(6):598-608.
Adhesion prevention in gynaecological surgery.
[Article in English, French]
Robertson D, Lefebvre G, Leyland N, Wolfman W, Allaire C, Awadalla A, Best C, Contestabile E, Dunn S, Heywood M, Leroux N, Potestio F, Rittenberg D, Senikas V, Soucy R, Singh S; Society of Obstetricians and Gynaecologists of Canada.
SourceToronto ON.
Abstract
OBJECTIVES: To review the etiology and incidence of and associative factors in the formation of adhesions following gynaecological surgery. To review evidence for the use of available means of adhesion prevention following gynaecological surgery.
OPTIONS: Women undergoing pelvic surgery are at risk of developing abdominal and/or pelvic adhesive disease postoperatively. Surgical technique and commercial adhesion prevention systems may decrease the risk of postoperative adhesion formation.
OUTCOMES: The outcomes measured are the incidence of postoperative adhesions, complications related to the formation of adhesions, and further intervention relative to adhesive disease.
EVIDENCE: Medline, EMBASE, and The Cochrane Library were searched for articles published in English from 1990 to March 2009, using appropriate controlled vocabulary and key words. Results were restricted to systematic reviews, randomized control trials/controlled clinical trials, cohort studies, and meta-analyses specifically addressing postoperative adhesions, adhesion prevention, and adhesive barriers. Searches were updated on a regular basis and incorporated in the guideline to March 2009. Grey (unpublished) literature was identified through searching the websites of health technology assessment and health technology assessment-related agencies, clinical practice guideline collections, clinical trial registries, and national and international medical specialty societies.
VALUES: The quality of evidence was rated using the criteria described in the Report of the Canadian Task Force on Preventive Health Care SUMMARY STATEMENTS: 1. Meticulous surgical technique is a means of preventing adhesions. This includes minimizing tissue trauma, achieving optimal hemostasis, minimizing the risk of infection, and avoiding contaminants (e.g., fecal matter) and the use of foreign materials (e.g., talcum powder) when possible. (II-2). 2. The risk of adhesions increases with the total number of abdominal and pelvic surgeries performed on one patient; every surgery needs to be carefully considered in this context. (II-2). 3. Polytetrafluoroethylene (Gore-Tex) barrier is more effective than no barrier or oxidized regenerated cellulose in preventing adhesion formation. (I). 4. Oxidized regenerated cellulose (Interceed) adhesion barrier is associated with a reduced incidence of pelvic adhesion formation at both laparoscopy and laparotomy when complete hemostasis is achieved. Oxidized regenerated cellulose may increase the risk of adhesions if optimal hemostasis is not achieved. (II-2). 5. Chemically modified sodium hyaluronate/carboxymethylcellulose (Seprafilm) is effective in preventing adhesion formation, especially following myomectomies. There is insufficient evidence on the effect of sodium hyaluronate/carboxymethylcellulose on long-term clinical outcomes such as fertility, chronic pelvic pain or small bowel obstruction. (II-2). 6. No adverse effects have been reported with the use of oxidized regenerated cellulose, polytetrafluoroethylene, or sodium hyaluronate/carboxymethylcellulose. (II-1). 7. Various pharmacological agents have been marketed as a means of preventing adhesions. None of these agents are presently available in Canada. There is insufficient evidence for the use of pharmacological agents in preventing adhesions. (III-C).
RECOMMENDATIONS: 1. Surgeons should attempt to perform surgical procedures using the least invasive method possible in order to decrease the risk of adhesion formation. (II-1B ). When feasible, for example, a laparoscopic surgical approach is preferable to an abdominal approach, and a vaginal or laparoscopic hysterectomy is preferable to an abdominal hysterectomy. 2. Precautions should be taken at surgery to minimize tissue trauma in order to decrease the risk of postoperative adhesions. These precautions include limiting packing, crushing, and manipulating of tissues to what is strictly required for safe completion of the procedure. (III-B). 3. Surgeons could consider using an adhesion barrier for patients who are at high risk of forming clinically significant adhesions (i.e., patients who have endometriosis or pelvic inflammatory disease or who are undergoing a myomectomy). If there is a risk of ongoing bleeding from the surgical site, oxidized regenerated cellulose (Interceed) should not be used as it may increase the risk of adhesions in this situation. (II-2B).
PMID:20569542[PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov/pubmed/20569542
Adhesion prevention in gynaecological surgery.
[Article in English, French]
Robertson D, Lefebvre G, Leyland N, Wolfman W, Allaire C, Awadalla A, Best C, Contestabile E, Dunn S, Heywood M, Leroux N, Potestio F, Rittenberg D, Senikas V, Soucy R, Singh S; Society of Obstetricians and Gynaecologists of Canada.
SourceToronto ON.
Abstract
OBJECTIVES: To review the etiology and incidence of and associative factors in the formation of adhesions following gynaecological surgery. To review evidence for the use of available means of adhesion prevention following gynaecological surgery.
OPTIONS: Women undergoing pelvic surgery are at risk of developing abdominal and/or pelvic adhesive disease postoperatively. Surgical technique and commercial adhesion prevention systems may decrease the risk of postoperative adhesion formation.
OUTCOMES: The outcomes measured are the incidence of postoperative adhesions, complications related to the formation of adhesions, and further intervention relative to adhesive disease.
EVIDENCE: Medline, EMBASE, and The Cochrane Library were searched for articles published in English from 1990 to March 2009, using appropriate controlled vocabulary and key words. Results were restricted to systematic reviews, randomized control trials/controlled clinical trials, cohort studies, and meta-analyses specifically addressing postoperative adhesions, adhesion prevention, and adhesive barriers. Searches were updated on a regular basis and incorporated in the guideline to March 2009. Grey (unpublished) literature was identified through searching the websites of health technology assessment and health technology assessment-related agencies, clinical practice guideline collections, clinical trial registries, and national and international medical specialty societies.
VALUES: The quality of evidence was rated using the criteria described in the Report of the Canadian Task Force on Preventive Health Care SUMMARY STATEMENTS: 1. Meticulous surgical technique is a means of preventing adhesions. This includes minimizing tissue trauma, achieving optimal hemostasis, minimizing the risk of infection, and avoiding contaminants (e.g., fecal matter) and the use of foreign materials (e.g., talcum powder) when possible. (II-2). 2. The risk of adhesions increases with the total number of abdominal and pelvic surgeries performed on one patient; every surgery needs to be carefully considered in this context. (II-2). 3. Polytetrafluoroethylene (Gore-Tex) barrier is more effective than no barrier or oxidized regenerated cellulose in preventing adhesion formation. (I). 4. Oxidized regenerated cellulose (Interceed) adhesion barrier is associated with a reduced incidence of pelvic adhesion formation at both laparoscopy and laparotomy when complete hemostasis is achieved. Oxidized regenerated cellulose may increase the risk of adhesions if optimal hemostasis is not achieved. (II-2). 5. Chemically modified sodium hyaluronate/carboxymethylcellulose (Seprafilm) is effective in preventing adhesion formation, especially following myomectomies. There is insufficient evidence on the effect of sodium hyaluronate/carboxymethylcellulose on long-term clinical outcomes such as fertility, chronic pelvic pain or small bowel obstruction. (II-2). 6. No adverse effects have been reported with the use of oxidized regenerated cellulose, polytetrafluoroethylene, or sodium hyaluronate/carboxymethylcellulose. (II-1). 7. Various pharmacological agents have been marketed as a means of preventing adhesions. None of these agents are presently available in Canada. There is insufficient evidence for the use of pharmacological agents in preventing adhesions. (III-C).
RECOMMENDATIONS: 1. Surgeons should attempt to perform surgical procedures using the least invasive method possible in order to decrease the risk of adhesion formation. (II-1B ). When feasible, for example, a laparoscopic surgical approach is preferable to an abdominal approach, and a vaginal or laparoscopic hysterectomy is preferable to an abdominal hysterectomy. 2. Precautions should be taken at surgery to minimize tissue trauma in order to decrease the risk of postoperative adhesions. These precautions include limiting packing, crushing, and manipulating of tissues to what is strictly required for safe completion of the procedure. (III-B). 3. Surgeons could consider using an adhesion barrier for patients who are at high risk of forming clinically significant adhesions (i.e., patients who have endometriosis or pelvic inflammatory disease or who are undergoing a myomectomy). If there is a risk of ongoing bleeding from the surgical site, oxidized regenerated cellulose (Interceed) should not be used as it may increase the risk of adhesions in this situation. (II-2B).
PMID:20569542[PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov/pubmed/20569542
Risk of adhesions and medicolegal issues UK ~ So how much should we tell patients?
Excerpt taken from http://onlinelibrary.wiley.com/doi/10.1576/toag.6.2.1.26993/pdf.
The Obstetrician & Gynaecologist
2004;6(2)
SUPPLEMENT
11
There are a number of quality and risk management
issues surrounding adhesions in surgery.The
surgical speciality has given rise to the highest
number and second highest value of negligence
claims reported to the UK National Health
Service Litigations Authority (NHSLA). The
highest numbers of reported Clinical Negligence
Scheme for Trusts (CNST) claims by speciality
are:
• surgery: 3365
• obstetrics and gynaecology 2237
• medicine 1278
• accident and emergency 803.23
Increasingly, complications resulting from
postoperative intra-abdominal adhesions have
been the subject of medical negligence cases.
These have included failure to diagnose adhesion related
problems, delay in diagnosis, bowel damage
at adhesiolysis, adhesive intestinal obstruction,
infertility or risk of infertility and failure to take
precautions to prevent adhesions. 24 Between
1994–1999, for example, the UK Medical
Defence Union received 77 adhesion-related
claims that resulted in 14 out of court settlements
in 11 years ranging from £7,960 to £124,261
(average £50,765 per case).24 The Medical
Defence Union is one of several insurers for the
private sector; figures are not available for claims
made by the National Health Service.
Anecdotal evidence suggests that the number of
claims and out of court settlements has increased
largely since then.
Duty of care
There is a duty of care to provide careful advice
and sufficient information upon which women
can reach a rational, informed decision on whether
to accept or refuse treatment. In negligence cases
people usually claim that insufficient information
was provided and that, if it had been provided,
consent would not have been granted.
So how is negligence established?
In order for this to be successful it is necessary to:
1) establish a duty of care
2) show a breach of this duty
3) demonstrate that this breach caused the injury.
All three aspects need to be present for negligence
to be established. Recently, in addition to this, the
UK Health Act has also established a duty of
quality.
The Bolam test of negligence (1957) had for
many years set the precedent in determining
negligence. This ruling stated that practitioners
are not negligent if they act in accordance with
practice accepted by a responsible body of
medical opinion. However, recent judgements
suggest that judges are moving away from
accepting what reasonable doctors might do,
towards supporting what reasonable patients
might expect. Recent case law suggests that the
Bolam test is being modified to enable a court to
reject medical opinion if it is not ‘reasonable or
responsible’.25 Physicians are required to understand
their obligations and have a duty to warn a
patient of any material risk inherent in a
proposed procedure, however small.
So how much should we tell patients? It is not
necessary to canvass every risk. However, it is
important to take account of the personality of
the patient, the likelihood of misfortune and what
in the way of warning is needed for the particular
patient’s welfare. Are gynaecologists and surgeons
informing patients about the risk of adhesions?
According to the International Adhesions Society
Patient Survey, the answer is no. Results from this
survey showed that adhesions were mentioned as
part of the consent process in only 10.4% of
cases.26 In 14.4% of cases, adhesions were discussed
but not as part of the consent process. For patients
undergoing adhesiolysis procedures, 54% were
given some information before surgery and 46%
were given specific information about antiadhesion
agents. In nonadhesiolysis procedures
only 10% of patients were advised about adhesions
and only 6% were given information on antiadhesion
agents.
Negligence cases relating to adhesions are
becoming more common. It is important to be
aware that the law governing negligence has
changed. Doctors are obliged to understand their
obligations and this will mean warning of the
risk of adhesions prior to abdominal or pelvic
surgery.
The Obstetrician & Gynaecologist
2004;6(2)
SUPPLEMENT
11
There are a number of quality and risk management
issues surrounding adhesions in surgery.The
surgical speciality has given rise to the highest
number and second highest value of negligence
claims reported to the UK National Health
Service Litigations Authority (NHSLA). The
highest numbers of reported Clinical Negligence
Scheme for Trusts (CNST) claims by speciality
are:
• surgery: 3365
• obstetrics and gynaecology 2237
• medicine 1278
• accident and emergency 803.23
Increasingly, complications resulting from
postoperative intra-abdominal adhesions have
been the subject of medical negligence cases.
These have included failure to diagnose adhesion related
problems, delay in diagnosis, bowel damage
at adhesiolysis, adhesive intestinal obstruction,
infertility or risk of infertility and failure to take
precautions to prevent adhesions. 24 Between
1994–1999, for example, the UK Medical
Defence Union received 77 adhesion-related
claims that resulted in 14 out of court settlements
in 11 years ranging from £7,960 to £124,261
(average £50,765 per case).24 The Medical
Defence Union is one of several insurers for the
private sector; figures are not available for claims
made by the National Health Service.
Anecdotal evidence suggests that the number of
claims and out of court settlements has increased
largely since then.
Duty of care
There is a duty of care to provide careful advice
and sufficient information upon which women
can reach a rational, informed decision on whether
to accept or refuse treatment. In negligence cases
people usually claim that insufficient information
was provided and that, if it had been provided,
consent would not have been granted.
So how is negligence established?
In order for this to be successful it is necessary to:
1) establish a duty of care
2) show a breach of this duty
3) demonstrate that this breach caused the injury.
All three aspects need to be present for negligence
to be established. Recently, in addition to this, the
UK Health Act has also established a duty of
quality.
The Bolam test of negligence (1957) had for
many years set the precedent in determining
negligence. This ruling stated that practitioners
are not negligent if they act in accordance with
practice accepted by a responsible body of
medical opinion. However, recent judgements
suggest that judges are moving away from
accepting what reasonable doctors might do,
towards supporting what reasonable patients
might expect. Recent case law suggests that the
Bolam test is being modified to enable a court to
reject medical opinion if it is not ‘reasonable or
responsible’.25 Physicians are required to understand
their obligations and have a duty to warn a
patient of any material risk inherent in a
proposed procedure, however small.
So how much should we tell patients? It is not
necessary to canvass every risk. However, it is
important to take account of the personality of
the patient, the likelihood of misfortune and what
in the way of warning is needed for the particular
patient’s welfare. Are gynaecologists and surgeons
informing patients about the risk of adhesions?
According to the International Adhesions Society
Patient Survey, the answer is no. Results from this
survey showed that adhesions were mentioned as
part of the consent process in only 10.4% of
cases.26 In 14.4% of cases, adhesions were discussed
but not as part of the consent process. For patients
undergoing adhesiolysis procedures, 54% were
given some information before surgery and 46%
were given specific information about antiadhesion
agents. In nonadhesiolysis procedures
only 10% of patients were advised about adhesions
and only 6% were given information on antiadhesion
agents.
Negligence cases relating to adhesions are
becoming more common. It is important to be
aware that the law governing negligence has
changed. Doctors are obliged to understand their
obligations and this will mean warning of the
risk of adhesions prior to abdominal or pelvic
surgery.
[Postoperative abdominal adhesions and their prevention in gynaecological surgery: I. What should you know?
Gynecol Obstet Fertil. 2011 Nov 28. [Epub ahead of print]
[Postoperative abdominal adhesions and their prevention in gynaecological surgery: I. What should you know?]
[Article in French]
Audebert A, Darai E, Bénifla JL, Yazbeck C, Déchaud H, Wattiez A, Crowe A, Pouly JL.
SourceService d'endoscopie gynécologique, polyclinique de Bordeaux, 145, rue du Tondu, 33000 Bordeaux, France.
Abstract
Adhesions are the most frequent complications of abdominopelvic surgery, causing important short- and long-term problems, including infertility, chronic pelvic pain and a lifetime risk of small bowel obstruction. They also complicate future surgery with increased morbidity and mortality risk. They pose serious quality of life issues for many patients with associated social and healthcare costs. Despite advances in surgical techniques, including laparoscopy, the healthcare burden of adhesion-related complications has not changed in recent years. Adhesiolysis remains the main treatment although adhesions reform in many patients. The extent of the problem of adhesions has been underestimated by surgeons and the health authorities. There is rising evidence however that surgeons can take important steps to reduce the impact of adhesions. As well as improvements in surgical technique, developments in adhesion-reduction strategies and new agents offer a realistic possibility of reducing adhesion formation and improving outcomes for patients. This paper is the first of a two-part publication providing a comprehensive overview of the evidence on adhesions to allow gynaecological surgeons to be best informed on adhesions, their development, impact on patients, health systems and surgical outcomes. In the second paper we review the various strategies to reduce the impact of adhesions and improve surgical outcomes to assist fellow surgeons in France to consider the adoption of adhesion reduction strategies in their own practice.
http://www.ncbi.nlm.nih.gov/pubmed/22129851
[Postoperative abdominal adhesions and their prevention in gynaecological surgery: I. What should you know?]
[Article in French]
Audebert A, Darai E, Bénifla JL, Yazbeck C, Déchaud H, Wattiez A, Crowe A, Pouly JL.
SourceService d'endoscopie gynécologique, polyclinique de Bordeaux, 145, rue du Tondu, 33000 Bordeaux, France.
Abstract
Adhesions are the most frequent complications of abdominopelvic surgery, causing important short- and long-term problems, including infertility, chronic pelvic pain and a lifetime risk of small bowel obstruction. They also complicate future surgery with increased morbidity and mortality risk. They pose serious quality of life issues for many patients with associated social and healthcare costs. Despite advances in surgical techniques, including laparoscopy, the healthcare burden of adhesion-related complications has not changed in recent years. Adhesiolysis remains the main treatment although adhesions reform in many patients. The extent of the problem of adhesions has been underestimated by surgeons and the health authorities. There is rising evidence however that surgeons can take important steps to reduce the impact of adhesions. As well as improvements in surgical technique, developments in adhesion-reduction strategies and new agents offer a realistic possibility of reducing adhesion formation and improving outcomes for patients. This paper is the first of a two-part publication providing a comprehensive overview of the evidence on adhesions to allow gynaecological surgeons to be best informed on adhesions, their development, impact on patients, health systems and surgical outcomes. In the second paper we review the various strategies to reduce the impact of adhesions and improve surgical outcomes to assist fellow surgeons in France to consider the adoption of adhesion reduction strategies in their own practice.
http://www.ncbi.nlm.nih.gov/pubmed/22129851
Adhesiolysis ~ 3-D Imaging of adhesiolysis and what you can expect from this procedure
3-D Imaging of adhesiolysis and what you can expect from this procedure.
http://www.youtube.com/watch?v=0EtueSRTRyY
http://www.youtube.com/watch?v=0EtueSRTRyY
Friday, December 02, 2011
Severe inflammatory reaction induced by peritoneal trauma is the key driving mechanism of postoperative adhesion formation
Many factors have been put forward as a driving mechanism of surgery-triggered adhesion formation (AF). In this study, we underline the key role of specific surgical trauma related with open surgery (OS) and laparoscopic (LS) conditions in postoperative AF and we aimed to study peritoneal tissue inflammatory reaction (TIR), remodelling specific complications of open surgery (OS) versus LS and subsequently evaluating AF induced by these conditions.
Methods: A prospective randomized study was done in 80 anaesthetised female Wistar rats divided equally into 2 groups.
Specific traumatic OS conditions were induced by midline incision line (MLI) extension and tissue drying and specific LS conditions were remodelled by CO2 insufflation. TIR was evaluated at the 24th, 72nd, 120th and 168th hour by scoring scale.
http://7thspace.com/headlines/399719/severe_inflammatory_reaction_induced_by_peritoneal_
trauma_is_the_key_driving_mechanism_of_postoperative_adhesion_formation_.html
Statistical analysis was performed by the non parametric t test and two-way ANOVA using Bonferroni post-tests.
Results: More pronounced residual TIR was registered after OS than after LS. There were no significant TIR interactions though highly significant differences were observed between the OS and LS groups (p<0.0001) with regard to surgical and time factors. The TIR change differences between the OS and LS groups were pronounced with postoperative time p<0.05 at the 24th and 72nd; p<0.01 - 120th and p<0.001 - 168th hrs. Adhesion free wounds were observed in 20.0 and 31.0% of cases after creation of OS and LS conditions respectively; with no significant differences between these values (p>0.05).
However larger adhesion size (41.6733.63) was observed after OS in comparison with LS (20.3116.38). The upper-lower 95% confidential limits ranged from 60.29 to 23.04 and from 29.04 to 11.59 respectively after OS and LS groups with significant differences (p=0.03).
Analogous changes were observed in adhesion severity values. Subsequently, severe TIR parameters were followed by larger sizes of severe postoperative adhesions in the OS group than those observed in the LS group.
Conclusions: MIL extension and tissue drying seem to be the key factors in the pathogenesis of adhesion formation, triggering severe inflammatory reactions of the peritoneal tissue surrounding the MIL resulting in local and systemic consequences.
CO2 insufflation however, led to moderate inflammation and less adhesion formation.
Author: Sergei PismenskyZhomart KalzhanovMarina EliseevaIoannis KosmasOspan Mynbaev
Credits/Source: BMC Surgery 2011, 11:30
Methods: A prospective randomized study was done in 80 anaesthetised female Wistar rats divided equally into 2 groups.
Specific traumatic OS conditions were induced by midline incision line (MLI) extension and tissue drying and specific LS conditions were remodelled by CO2 insufflation. TIR was evaluated at the 24th, 72nd, 120th and 168th hour by scoring scale.
http://7thspace.com/headlines/399719/severe_inflammatory_reaction_induced_by_peritoneal_
trauma_is_the_key_driving_mechanism_of_postoperative_adhesion_formation_.html
Statistical analysis was performed by the non parametric t test and two-way ANOVA using Bonferroni post-tests.
Results: More pronounced residual TIR was registered after OS than after LS. There were no significant TIR interactions though highly significant differences were observed between the OS and LS groups (p<0.0001) with regard to surgical and time factors. The TIR change differences between the OS and LS groups were pronounced with postoperative time p<0.05 at the 24th and 72nd; p<0.01 - 120th and p<0.001 - 168th hrs. Adhesion free wounds were observed in 20.0 and 31.0% of cases after creation of OS and LS conditions respectively; with no significant differences between these values (p>0.05).
However larger adhesion size (41.6733.63) was observed after OS in comparison with LS (20.3116.38). The upper-lower 95% confidential limits ranged from 60.29 to 23.04 and from 29.04 to 11.59 respectively after OS and LS groups with significant differences (p=0.03).
Analogous changes were observed in adhesion severity values. Subsequently, severe TIR parameters were followed by larger sizes of severe postoperative adhesions in the OS group than those observed in the LS group.
Conclusions: MIL extension and tissue drying seem to be the key factors in the pathogenesis of adhesion formation, triggering severe inflammatory reactions of the peritoneal tissue surrounding the MIL resulting in local and systemic consequences.
CO2 insufflation however, led to moderate inflammation and less adhesion formation.
Author: Sergei PismenskyZhomart KalzhanovMarina EliseevaIoannis KosmasOspan Mynbaev
Credits/Source: BMC Surgery 2011, 11:30
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