Australian Safety and Efficacy Register of New Interventional Procedures-Surgical. Systematic Review. August 2006

Transcription

1 ASERNIP S Australian Safety and Efficacy Register of New Interventional Procedures-Surgical Systematic Review Self-expanding Metallic Stents (SEMS) for Relieving Malignant Colorectal Obstruction: A Systematic Review ASERNIP-S REPORT NO. 49 August 2006 Australian Safety & Efficacy Register of New Interventional Procedures Surgical The Royal Australasian College of Surgeons

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3 Self-expanding Metallic Stents (SEMS) for Relieving Malignant Colorectal Obstruction: A Systematic Review ISBN Published August 2006 This report should be cited in the following manner: Watt A, et al. Self-expanding metallic stents (SEMS) for relieving malignant colorectal obstruction: a systematic review. ASERNIP-S Report No. 49. Adelaide, South Australia: ASERNIP-S, August Copies of these reports can be obtained from: ASERNIP-S PO Box 553, Stepney, SA 5069 AUSTRALIA Ph: Fax: college.asernip@surgeons.org i

4 - ASERNIP-S REVIEW OF SELF-EXPANDING METALLIC STENTS AUGUST The Safety and Efficacy Classification for the Systematic Review of Self-expanding Metallic Stents for Relieving Malignant Colorectal Obstructions was ratified by: The ASERNIP-S Management Committee on July 31, 2006 and The Council of the Royal Australasian College of Surgeons on August 26, 2006 ii

5 - ASERNIP-S REVIEW OF SELF-EXPANDING METALLIC STENTS AUGUST Table of Contents Executive Summary...viii The ASERNIP-S Classification System...xi The ASERNIP-S Review Group...xiii 1. Introduction... 1 Objective...1 Background...1 Malignant colorectal obstruction...1 Conventional therapies for relieving malignant colorectal obstruction...1 Self-expanding metallic stents (SEMS) for relieving colorectal obstruction...3 Summary Methods... 7 Literature Search Protocol...7 Inclusion Criteria...7 Exclusion Criteria...7 Types of Studies...7 Language Restriction...7 Literature Search Strategies...7 Databases Searched and Search Terms Used...7 Methods of the Review...7 Literature Database...7 Ongoing and Unpublished Trials...7 Data Extraction...7 Data Analysis Studies Included in the Review... 7 Designation of Levels of Evidence and Critical Appraisal...7 Description of Studies Results... 7 Efficacy of SEMS placement...7 Technical and clinical success...7 Duration of patency palliative stent placement...7 Progression to surgery bridge-to-surgery stent placement...7 iii

6 - ASERNIP-S REVIEW OF SELF-EXPANDING METALLIC STENTS AUGUST Re-intervention...7 Safety of SEMS placement...7 Stent migration...7 Perforation...7 Re-obstruction...7 Other complications...7 Efficacy of SEMS versus surgery...7 Technical and clinical success...7 Length of hospital stay...7 Safety of SEMS versus surgery...7 Complications...7 Post-operative mortality...7 Survival...7 Efficacy of elective surgery with SEMS versus emergency surgery...7 Technical and clinical success of SEMS placement...7 Progression to elective surgery after SEMS placement...7 Rate of primary anastomosis and colostomy...7 Length of hospital stay...7 Safety of elective surgery with SEMS versus emergency surgery...7 Complications...7 Post-operative mortality...7 Efficacy of covered SEMS versus uncovered SEMS...7 Technical and clinical success...7 Safety of covered SEMS versus uncovered SEMS...7 Stent migration...7 Perforation...7 Re-obstruction...7 Cost considerations Discussion... 7 Study Limitations...7 SEMS placement...7 Efficacy...7 Safety...7 SEMS versus surgery...7 iv

7 - ASERNIP-S REVIEW OF SELF-EXPANDING METALLIC STENTS AUGUST Elective surgery with SEMS versus emergency surgery...7 Covered SEMS versus uncovered SEMS...7 Cost considerations...7 Future research Conclusions and Recommendations... 7 Classification and Recommendations...7 Efficacy...7 Clinical and Research Recommendations...7 Acknowledgments...7 References... 7 Appendix A Hierarchy Of Evidence...7 Appendix B Excluded Studies...7 Appendix C Safety and Efficacy Outcomes: Complete Data Tables...7 Appendix D Methodological Assessment and Data Extraction Tables...7 v

8 - ASERNIP-S REVIEW OF SELF-EXPANDING METALLIC STENTS AUGUST List of Tables Table 1. TGA-approved stenting devices and systems for treating colorectal obstruction...4 Table 2. Databases searched...7 Table 3. Summary of included comparative studies...7 Table 4. Summary of included case series...7 Table 5. Summary of included case reports...7 Table 6. Technical and clinical success summary...7 Table 7. Mean duration of SEMS patency in patients with stents placed for palliation...7 Table 8. Proportion of patients with patent stents at time of death or end of follow up...7 Table 9. Time to surgery in patients with SEMS placed as a bridge-to-surgery...7 Table 10. Re-intervention details...7 Table 11. Migration details...7 Table 12. Perforation details...7 Table 13. Re-obstruction details...7 Table 14. Complications as a result of SEMS placement...7 Table 15. Summary of SEMS versus surgery comparative studies...7 Table 16. Technical & clinical success rates of SEMS placement and surgery...7 Table 17. Length of hospital stay (LOS) in SEMS & surgery patients...7 Table 18. Complications arising after SEMS placement & emergency surgery...7 Table 19. Complications arising after SEMS placement & unspecified surgery...7 Table 20. Survival after SEMS comparerd to surgery...7 Table 21. Summary of elective versus emergency surgery comparative studies...7 Table 22. Technical & clinical success rates of SEMS placement...7 Table 23. Rates of primary anastomosis and colostomy in elective and emergency surgery...7 Table 24. Length of hospital stay for elective & emergency surgery patients...7 Table 25. Complications after elective and emergency surgery...7 vi

9 - ASERNIP-S REVIEW OF SELF-EXPANDING METALLIC STENTS AUGUST Table 26. Efficacy of covered versus uncovered stents... 7 Table 27. Migration details covered versus uncovered stents... 7 Table 28. Perforation details covered stents... 7 Table 29. Perforation details uncovered stents... 7 Table 30. Re-obstruction details... 7 Table 31. Overall costs of SEMS placement with elective surgery compared to emergency surgery... 7 Table 32. Overall costs of SEMS placement compared to surgery... 7 Table 33. Excluded studies... 7 Table 34. Technical and clinical success of SEMS placement - all included studies... 7 Table 35. Technical and clinical success of palliative SEMS placement... 7 Table 36. Technical and clinical success of bridge-to-surgery SEMS placement... 7 Table 37. Technical and clinical success of SEMS placement stratified by underlying disease... 7 Table 38. Technical and clinical success of SEMS placement in patients with primary and recurrent colorectal cancer... 7 Table 39. Migration details - all studies... 7 Table 40. Perforation details all studies... 7 Table 41. Re-obstruction details - all studies... 7 vii

10 - ASERNIP-S REVIEW OF SELF-EXPANDING METALLIC STENTS AUGUST Executive Summary Objective To assess the safety and efficacy of self-expanding metallic stents (SEMS) for relieving malignant colorectal obstruction compared with surgical techniques, on the basis of a systematic assessment of the literature. Methods Search strategy Studies were identified by searching MEDLINE, EMBASE, CINAHL, Current Contents, Science Citation Index, PubMed and the NHS Centre for Reviews and Dissemination Database in April Clinical Trials Database (US), National Research Register (UK), Current Controlled Trials, the Cochrane Library, Australian Clinical Trials Registry and ACP Journal Club were also searched in April 2005 and updated in February Additional articles were identified through the reference sections of the articles retrieved. Study selection Randomised controlled trials, historical and/or non-randomised comparative studies, case series and case reports reporting complications were included for review. Included comparative studies concerned the comparative interventions, defined as surgical intervention or any internal comparison of different types of stent. Efficacy outcomes included technical and clinical success, duration of patency, progression to surgery and rates of re-intervention, anastomosis and colostomy. Safety outcomes included complications such as perforation, migration and stent obstruction. Data collection and analysis Data from the included studies were extracted by the ASERNIP-S researcher using standardised data extraction tables developed a priori and checked by a second researcher. Statistical pooling was judged to be inappropriate for this data set, but narrative pooling was utilised where appropriate. Data have been stratified where possible by intent of stent placement (palliative or bridge-to-surgery) and patient population. Results A total of 15 comparative studies and 73 case series were identified for inclusion in this review. There were nine studies comparing SEMS to surgery (of which two were randomised controlled trials), three studies comparing elective surgery after decompression with SEMS to emergency surgery and two studies comparing covered and uncovered stents. The review was limited by the quality and quantity of the available evidence. Many of the included studies suffered from a lack of methodological rigour, which made viii

11 - ASERNIP-S REVIEW OF SELF-EXPANDING METALLIC STENTS AUGUST assessing the validity of the data difficult. Not all studies reported all outcomes for different patient populations, further reducing the size of the evidence base. However, despite a poor quality evidence base, the available data suggested that SEMS placement was safe and effective in overcoming left-sided malignant colorectal obstructions, regardless of the indication for stent placement or underlying disease. Additionally, SEMS placement had positive outcomes when compared to surgery, including overall shorter hospital stays and a lower rate of serious adverse events. Post-operative mortality appeared comparable between the two interventions. Combining SEMS placement with elective surgery also appeared safer and more effective than emergency surgery, with higher rates of primary anastomosis, lower rates of colostomy, shorter hospital stays and lower overall complication rates. However, the small sample sizes of the included studies limited the validity of these findings. Classification and Recommendations On the basis of the evidence presented in this systematic review, the ASERNIP-S Review Group agreed on the following classifications and recommendations concerning the safety and efficacy of self-expanding metallic stents: Classifications Evidence rating The evidence base in this review is rated as poor. Safety The safety of SEMS placement compared to surgery cannot be determined from this evidence base. However, considered in isolation, the evidence included in this review (primarily from case series and case reports) suggests that SEMS placement is a safe procedure for relieving left-sided colorectal obstructions. Efficacy The efficacy of SEMS placement compared to surgery cannot be determined from this evidence base. However, considered in isolation, the evidence included in this review (primarily from case series and case reports) suggests that SEMS placement is an effective procedure for relieving left-sided colorectal obstructions, with high levels of technical and clinical success. Recommendations Current trials in progress may assist in further defining the clinical role of SEMS placement for the treatment of malignant colorectal obstructions, particularly those ix

12 - ASERNIP-S REVIEW OF SELF-EXPANDING METALLIC STENTS AUGUST that evaluate patient-related outcomes. Additional comparative studies would increase the certainty of the conclusions that can be drawn. Important note The information contained in this report is a distillation of the best available evidence located at the time the searches were completed as stated in the protocol. Please consult with your medical practitioner if you have further questions relating to the information provided, as the clinical context may vary from patient to patient. x

13 - ASERNIP-S REVIEW OF SELF-EXPANDING METALLIC STENTS AUGUST The ASERNIP-S Classification System Evidence Rating The evidence for ASERNIP-S systematic reviews is classified as Good, Average or Poor, based on the quality and availability of this evidence. High quality evidence is defined here as having a low risk of bias and no other significant flaws. While high quality randomised controlled trials are regarded as the best kind of evidence for comparing interventions, it may not be practical or ethical to undertake them for some surgical procedures, or the relevant randomised controlled trials may not yet have been carried out. This means that it may not be possible for the evidence on some procedures to be classified as good. Good Most of the evidence is from a high quality systematic review of all relevant randomised trials or from at least one high quality randomised controlled trial of sufficient power. The component studies should show consistent results, the differences between the interventions being compared should be large enough to be important, and the results should be precise with minimal uncertainty. Average Most of the evidence is from high quality quasi-randomised controlled trials, or from non-randomised comparative studies without significant flaws, such as large losses to follow-up and obvious baseline differences between the comparison groups. There is a greater risk of bias, confounding and chance relationships compared to high-quality randomised controlled trials, but there is still a moderate probability that the relationships are causal. An inconclusive systematic review based on small randomised controlled trials that lack the power to detect a difference between interventions and randomized controlled trials of moderate or uncertain quality may attract a rating of average. Poor Most of the evidence is from case series, or studies of the above designs with significant flaws or a high risk of bias. A poor rating may also be given if there is insufficient evidence. xi

14 - ASERNIP-S REVIEW OF SELF-EXPANDING METALLIC STENTS AUGUST Safety and Efficacy Classification Safety At least as safe compared to comparator * procedure(s) This grading is based on the systematic review showing that the new intervention is at least as safe as the comparator. Safety cannot be determined This grading is given if the evidence is insufficient to determine the safety of the new intervention. Less safe compared to comparator * procedure(s) This grading is based on the systematic review showing that the new intervention is not as safe as the comparator. Efficacy At least as efficacious compared to comparator * procedure(s) This grading is based on the systematic review showing that the new intervention is at least as efficacious as the comparator. Efficacy cannot be determined This grading is given if the evidence is insufficient to determine the efficacy of the new intervention. Less efficacious compared to comparator * procedure(s) This grading is based on the systematic review showing that the new intervention is not as efficacious as the comparator. Research Recommendations It may be recommended that an audit or a controlled (ideally randomised) clinical trial be undertaken in order to strengthen the evidence base. Clinical Recommendations Additional recommendations for use of the new intervention in clinical practice may be provided to ensure appropriate use of the procedure by sufficiently qualified/ experienced centres and on specific patient types (where appropriate). * A comparator may be the current gold standard procedure, and alternative procedure, a non-surgical procedure or no treatment (natural history) xii

15 - ASERNIP-S REVIEW OF SELF-EXPANDING METALLIC STENTS AUGUST The ASERNIP-S Review Group ASERNIP-S Director Professor Guy Maddern ASERNIP-S Royal Australasian College of Surgeons Stepney SA 5069 Advisory Surgeons Associate Professor Nicholas Rieger University of Adelaide Adelaide SA 5000 The Queen Elizabeth Hospital Woodville Road Woodville SA 5011 Mr Ian Faragher Department of Surgery Western Hospital Footscray VIC 3011 ASERNIP-S Researchers Ms Amber Watt Dr Tabatha Griffin Ms Elen Shute ASERNIP-S Royal Australasian College of Surgeons Stepney SA 5069 Conflict of interest statement None of the authors declared a conflict of interest. xiii

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17 - ASERNIP-S REVIEW OF SELF-EXPANDING METALLIC STENTS AUGUST Introduction Objective To assess the safety and efficacy of self-expanding metallic stents (SEMS) for relieving malignant colorectal obstruction compared with surgical techniques, based on a systematic assessment of the literature. Background Malignant colorectal obstruction Cancer of the colon and rectum, also known as colorectal or bowel cancer, is diagnosed in over 6,000 males and 5,000 females each year in Australia at current rates, one in seventeen males and one in twenty-six females will be affected by colorectal cancer before the age of seventy-five (de Looper and Bhatai 2001). Colorectal and ovarian primary tumours are the most common cause of malignant obstruction (Davis and Nouneh 2001), but other cancers may also be implicated. Acute or sub-acute bowel obstruction can lead to symptoms such as abdominal pain, nausea, vomiting, dehydration, diarrhoea, constipation and bleeding. Symptoms rarely resolve spontaneously and without treatment, most patients will deteriorate, with the condition characterised by increased pain, distress, possible faeculent vomiting, bowel rupture and eventual death. Patients with less advanced cancer and who are in good general condition are likely to be candidates for surgical resection of the obstructing tumour. Resection, as described below, is unlikely to be appropriate for patients with advanced metastatic disease, or those with severe comorbidities. A number of treatment options are available to relieve obstruction in these nonresectable cases, and these are outlined below. Conventional therapies for relieving malignant colorectal obstruction Surgical treatment Resection Around half of patients presenting with malignant colorectal obstruction are candidates for potentially curative resection surgery (Xinopoulos 2004). Resection may be carried out as a one-stage, two-stage or even three-stage procedure. For rightsided malignancies, a hemicolectomy with anastomosis is generally performed as a one-stage procedure: the diseased section of bowel is excised and removed, and the free ends of the bowel are rejoined during the same procedure to restore bowel function. Left-sided malignancies are also commonly treated in this way, but a twostage procedure may also be undertaken. A two-stage procedure involves resection of SECTION 1 INTRODUCTION 1

18 - ASERNIP-S REVIEW OF SELF-EXPANDING METALLIC STENTS AUGUST the bowel and the formation of a stoma, followed by a second operation to restore bowel continuity (Hartmann s procedure). Alternatively, the stoma may be closed during a third procedure (De Salvo et al. 2004). However, a significant proportion of patients receiving a staged procedure never undergo reversal of the colostomy (Mauro et al. 2000). It is currently unclear whether a single or staged resection is safer and more effective (De Salvo et al. 2004), but emergency surgery carries a higher risk than elective surgery (McArdle and Hole 2004). Palliative colostomy Permanent stoma creation is the standard treatment for bowel obstruction caused by non-resectable tumours. As with the staged resection procedure described above, stoma surgery relieves the symptoms of obstruction by diverting the bowel contents away from the occluded segment and out of the body through a stoma created in the abdominal wall. Faeces are collected in a disposable colostomy bag, which must be changed regularly. Unlike a staged resection, however, patients receiving a colostomy as a palliative measure do not have it reversed at a later date, and will live with a stoma until their death. Although it is a standard treatment modality, stoma surgery is associated with high morbidity and mortality rates, probably due to the advanced age and poor general health status of the patient population. Furthermore, stoma creation is recognised as having a high negative impact on patients psychosocial wellbeing (Karadağ et al. 2003), and can be a burden to carers as well as the patient during the final months of their life. Endoscopic ablation Endoscopic treatments to palliate rectal obstruction have been developed in recent years, and are not yet a standard treatment option. Treatments include cryotherapy, electrocoagulation, argon plasma coagulation and photodynamic therapy, but Nd:YAG (neodymium yttrium argon garnet) laser therapy is the most commonly used endoscopic ablation technique (Kimmey 2004). Laser therapy is generally used as an adjunct to other treatments such as radiotherapy or stenting. It can restore patency when used on its own, but re-obstruction usually occurs quite rapidly (Kimmey 2004). Its use is restricted to non-resectable tumours because of the risk of perforation and tumour seeding (Mauro 2000). Medical management Medical management is most commonly utilised in hospices and palliative care settings to assist in maintaining an acceptable quality of life in patients with terminal disease (Feuer and Broadley 1999). This form of management is most likely to be effective if the obstruction is higher up the intestinal tract, and if the obstruction is partial rather than complete (Davis and Nouneh 2001). Opioids and anticholinergics may be used to treat pain, and anti-emetics can control nausea and vomiting. However, these techniques may also be used in hospitals to improve patient 2 SECTION 1 INTRODUCTION

19 - ASERNIP-S REVIEW OF SELF-EXPANDING METALLIC STENTS AUGUST condition by increasing hydration and restoring electrolyte balance, allowing surgical intervention to be undertaken more safely. Increasingly, corticosteroids are being used palliatively to treat bowel obstruction and its concomitants, nausea, pain and vomiting. These drugs are anti-emetics and coanalgesics, and their anti-inflammatory properties may reduce peri-tumour oedema and so relieve obstruction. Despite their widespread use, however, the safety and efficacy of corticosteroids in colorectal obstruction is unclear (Hardy et al. 1997). Further studies in this area need to be carried out in the future (Feuer and Broadley 1999). Self-expanding metallic stents (SEMS) for relieving colorectal obstruction Self-expanding metallic stents (SEMS) are expandable metallic tubes that are used to treat obstructions in a wide variety of conditions and anatomical locations, and they are available in many different designs and sizes depending upon their intended application. They are advanced to the obstruction in a collapsed state, and once deployed, they slowly open to their maximum diameter under their own force. This achieves patency of the obstructed anatomy. The value of stent placement is as a minimally invasive alternative to open surgical techniques. Following successful application of stenting in blood vessels and the upper gastrointestinal tract, stenting has in recent years been adopted for the relief of malignant colorectal obstruction. For this indication, stenting is an alternative to invasive emergency abdominal surgery, such as resection or stoma creation. SEMS may be employed as a definitive palliative measure, or they can be used as a bridge-to-surgery to allow stabilisation of the patient s condition before surgery is carried out as an elective procedure at a later date (see clinical decision pathway, summarised in Figure 1). Although this review only considers stents used to relieve malignant colorectal obstruction, it should be noted that the technique is also used to treat benign obstructions caused by conditions such as Crohn s disease. Devices Initially, colorectal stenting was undertaken with metallic stents designed for use in other anatomical locations such as the oesophagus and the trachea/bronchi, and in some instances plastic stents were also used (e.g. Dohmoto 1997). Plastic stents appear to have been abandoned early on because of their large calibre and inflexible structure. Increasing use of colorectal stenting has now led to the development of SEMS specifically for use in the lower gastrointestinal tract. These include devices such as the Wallstent Enteral colonic and duodenal endoprosthesis, the Ultraflex Precision Colonic Stent System and the Cook Colonic Z-Stent, which are all approved for use in Australia (see Table 1). Other devices such as the Mostech Rectal/Colonic Stent (Mostech, 2005) are not approved for use in Australia, but are SECTION 1 INTRODUCTION 3

20 - ASERNIP-S REVIEW OF SELF-EXPANDING METALLIC STENTS AUGUST used internationally. Colorectal stents are available in a variety of lengths and diameters, and the appropriate stent can be chosen based on factors such as the length of the obstructed section of bowel and anatomical location of the obstruction. Covered and uncovered SEMS have been used in the treatment of colorectal obstruction. Both types comprise a metallic mesh tube, but covered stents also have a smooth coating of a substance such as polyethylene or silicone. The purpose of the coating is to prevent tumour ingrowth through the wire mesh of the stent body. However, uncovered stents have the advantage of greater flexibility, which makes them easier to advance through tortuous anatomy. Some covered stents are covered for their entire length, but others have exposed ends to allow the device to anchor more securely to the bowel wall and so reduce the chances of displacement. To further reduce the chances of stent migration, colorectal stents are generally flared at one or both ends. Table 1. TGA-approved stenting devices and systems for treating colorectal obstruction Name of device Manufacturer ARTG No.* Product No. Ultraflex Precision Colonic Stent System Boston Scientific Pty Ltd Wallstent Enteral (Colonic/Duodenal) Boston Scientific Pty Ltd Colonic Z Stent with Introduction System *ARTG = Australian Register of Therapeutic Goods William A. Cook Australia Pty Ltd Stent delivery Colorectal stenting involves loading the device into a delivery system which constrains it radially, advancing the collapsed stent to the narrowed section of bowel, then releasing it inside the obstruction and withdrawing the delivery system. Early on in colorectal stenting experience, the obstructed section of bowel was often predilated using a balloon catheter to allow easier stent insertion. This practice has now largely been discontinued due to the risk of bowel rupture. After placement, the device expands radially under its own force, thereby restoring luminal patency. Almost all colorectal stenting procedures are carried out transanally, but Gomez et al. (2001) demonstrated the possibility of percutaneous colorectal stent delivery in a patient in whom endoscopic delivery had failed, and Miyayama et al. (2000) successfully delivered a stent via a previously-created colostomy. Unlike open surgery, which requires a general anaesthetic, it is usual for colorectal stenting to be carried out either under conscious sedation or without any anaesthesia, and it is generally well tolerated by patients. This reduces the risks associated with general anaesthetic use for open abdominal surgery. Fluoroscopic and/or endoscopic guidance is used to correctly position the stent within the stricture. Abdominal 4 SECTION 1 INTRODUCTION

21 - ASERNIP-S REVIEW OF SELF-EXPANDING METALLIC STENTS AUGUST radiography may be used at intervals in the first few days after stent placement to ascertain that the stent has remained correctly placed and that the obstructing lesion is patent. Possible complications of stenting There are some known potential complications associated with colorectal stenting. These include: device failure such as fracture; stent migration; re-obstruction; bowel perforation; tenesmus; bleeding and anal/abdominal pain. Summary Malignant colorectal obstruction is increasingly being treated by the endoluminal placement of self-expanding metallic stents. This minimally invasive procedure shows promise as a definitive palliative treatment, and has the potential to replace stoma creation in these cases. As a bridge-to-surgery, SEMS placement could reduce the high morbidity and mortality rates associated with emergency surgery. Before SEMS placement can be adopted with confidence, there is a need for rigorous assessment of the procedure s safety and efficacy: this is the primary objective of this review. Stenting will be compared with conventional treatments, and where possible, internal comparisons will be made between different devices, placement locations, and indications. SECTION 1 INTRODUCTION 5

22 - ASERNIP-S REVIEW OF SELF-EXPANDING METALLIC STENTS AUGUST Figure 1. Clinical decision pathway Large bowel obstruction due to primary colorectal cancer Resectable (curative) Non-resectable / metastases present Emergency or elective Emergency or elective Single-stage procedure Two-stage procedure Three-stage procedure Medication Stoma formation SEMS (palliative) SEMS (bridge-tosurgery) Resection & anastomosis Resection & stoma formation Stoma formation Resection Restoration of continuity Resection Stoma closure 6 SECTION 1 INTRODUCTION

23 - ASERNIP-S REVIEW OF SELF-EXPANDING METALLIC STENTS AUGUST Methods Literature Search Protocol Inclusion Criteria Papers were selected for inclusion in this systematic review on the basis of the following criteria: Participants Only human studies, specifically of patients aged 18 years or over, diagnosed with malignant colorectal obstruction, were included for review. Studies including patients with benign colorectal obstructions were excluded unless their results could be separated from the aggregate data. New Intervention Studies were included if they concerned the new intervention, defined as the use of self-expanding metallic stents for the treatment of malignant colorectal obstruction. Studies used any of the commercially available self-expanding metallic stents and delivery systems, and stents could be placed anywhere in the colon or rectum. Comparative Intervention Comparative studies were included if they compared SEMS with surgical, medical or endoscopic management of malignant colorectal obstruction. Studies comparing different types of stents (e.g. covered versus uncovered) were also included. Outcomes The papers included contained information on at least one of the following outcomes of the new or comparative interventions: Perioperative and postoperative morbidity of patients which could include, but not be limited to: Stroke or other thromboembolism Myocardial infarction Bleeding Bowel perforation Peritonitis or other infection Pain Perioperative and early postoperative factors for patients which could include, but not be limited to: Operation time Early re-intervention Readmission SECTION 2 METHODS 7

24 - ASERNIP-S REVIEW OF SELF-EXPANDING METALLIC STENTS AUGUST Need to place a second stent Restenosis Successful stent deployment Device failure or migration Relief of symptoms such as nausea or vomiting Bowel motility Convalescence of patients which could include, but not be limited to: Postoperative care requirements Length of hospital stay Quality of life measures Return to normal eating/bowel habits Progression to elective surgery (bridge-to-surgery patients) Durability of treatment which could include, but not be limited to: Need for further intervention (planned and unplanned) Duration of patency Stent migration Durability of symptom relief Survival Cost/resource use Exclusion Criteria Studies that reported only on the following were excluded: Animal studies Stenting of benign colorectal obstructions Stenting higher up the gastrointestinal tract than the colon (e.g. duodenum) Case reports not reporting complications Data on stents that are not commercially available Types of Studies Randomised controlled trials (RCTs), historical and/or non-randomised comparative studies, case series and case reports (reporting complications) were included for review. Where appropriate, additional relevant published material in the form of letters, conference material, commentary, editorials and abstracts was included as background information. In the case of duplicate publications, the latest and most complete study was included and any potential for duplicate reporting published under multiple authors was noted. 8 SECTION 2 METHODS

25 - ASERNIP-S REVIEW OF SELF-EXPANDING METALLIC STENTS AUGUST Language Restriction Searches were conducted without language restriction. Foreign language papers were subsequently included on a case-by-case basis when they were considered to be likely to add information to the existing evidence base. The English abstracts of foreign language articles were also included where they were judged to meet the study inclusion criteria and contain safety and efficacy data. SECTION 2 METHODS 9

26 - ASERNIP-S REVIEW OF SELF-EXPANDING METALLIC STENTS AUGUST Literature Search Strategies Databases Searched and Search Terms Used Searches are shown in Table 2. Table 2. Databases searched Database Platform Search terms Search date MEDLINE Ovid 1. exp *Intestinal Obstruction April exp *STENTS/ 3. 1 AND 2 EMBASE Ovid 1. exp *STENT/ April exp *Intestine Obstruction CINAHL (Cumulative Index to Nursing and Allied Health Care) Current Contents Science Citation Index Ovid ISI Web of Knowledge Web of Science 3. 1 AND 2 1. exp *STENTS/ 2. exp *Intestinal Obstruction 3. 1 AND 2 1. ts=colorectal 2. ts=stent* 3. sc=1 AND 2 1. ts=colorectal 2. ts=stent* 3. #1 AND #2 PubMed NLM ( Intestinal Obstruction/radiography [MeSH] OR Intestinal Obstruction/surgery [MeSH] OR Intestinal Obstruction/therapy [MeSH]) AND Stents [MeSH] NHS Centre for Reviews and Dissemination Database April 2005 April 2005 April 2005 April 2005 Web Stent AND Colorectal April 2005 Clinicaltrials.gov Web Colorectal stent February 2006 Current Controlled Trials Web Colorectal stent February 2006 Cochrane Library Web Stent AND Colorectal February 2006 ACP Journal Club Web Stents February 2006 National Research Register (UK) Australian Clinical Trials Registry Web 1. exp *Intestinal Obstruction 2. exp *STENTS/ 3. 1 AND 2 February 2006 Web Colorectal March 2006 NOTE: * is a truncation character that retrieves all possible suffix variations of the root word e.g. surg* retrieves surgery, surgical, surgeon, etc. In Cochrane the truncation character is *; in Current Contents, Embase and Medline (Ovid) it is $. # is a wildcard symbol that substitutes for one required character in Current Contents, Embase and Medline (Ovid). Methods of the Review Literature Database Articles were retrieved when they were judged to possibly meet the selection criteria. Two reviewers then independently applied the selection criteria to these retrieved papers (or abstracts). Any differences were resolved by discussion with another reviewer. In some cases, when the full text of the article was retrieved, closer examination revealed that it did not meet the inclusion criteria specified by the 10 SECTION 2 METHODS

27 - ASERNIP-S REVIEW OF SELF-EXPANDING METALLIC STENTS AUGUST review protocol. Consequently these papers were not used to formulate the evidence base for the systematic review (see Appendix B). However, relevant information contained in these excluded papers was used to inform and expand the review discussion. The bibliographies of all publications retrieved were manually searched for relevant references that may have been missed in the database search (pearling). Ongoing and Unpublished Trials From searches of the Clinical Trials Database, NHS CRD, NHS HTA and the National Research Register, three potentially significant trials were identified. One multicentre trial is recruiting at least 140 patients in centres across Europe to evaluate the clinical outcome and potential cost-benefit of preoperative endoluminal stenting of obstructing left sided colorectal lesions compared to urgent surgical decompression. The study appears to still be open for recruitment, and complete details can be viewed at: A large United States-based trial (ClinicalTrials.gov Identifier: NCT ) is also currently recruiting 180 participants to evaluate patients with malignant large bowel obstruction who undergo palliative treatment with minimally invasive surgical diversion or endoscopic colorectal stent placement in terms of quality of life, symptom relief and treatment-related complications. Additionally, an Australian study (ACTR Number: ACTRN ) has been registered, with an expected start date of 30 May 2006 listed. The investigators aim to enrol 142 patients in a randomised controlled trial to compare the outcomes of colorectal surgery versus stent insertion in the treatment of non-curable colorectal cancer. The primary outcome will be a comparison of quality of life in the first 12 months following the procedure. Secondary outcomes will include an examination of the permanent stoma rate, length of procedure, intensive care and hospital stay, complication rate, 30-day mortality rate and cost utility. Data Extraction One reviewer extracted data onto data extraction sheets designed for this review and a second reviewer checked the data extraction. Data were only reported if stated in the text, tables, graphs or figures of the article, or could be accurately extrapolated from the data presented. If no data were reported for a particular outcome, in particular adverse outcomes, then no value was tabulated. This was done to avoid the bias caused by incorrectly assigning a value of zero to an outcome measurement on the basis of an unverified assumption by the reviewer. For example, if no mortality rate was reported the result was not assumed to be zero. All results are tabulated in Appendices D.1 to D.5. SECTION 2 METHODS 11

28 - ASERNIP-S REVIEW OF SELF-EXPANDING METALLIC STENTS AUGUST Data Analysis Statistical pooling of studies was judged not to be appropriate. A number of comparisons were planned, but could not be investigated further due to lack of reported data. Data has been stratified where possible by intent of stent placement (palliative or bridge-to-surgery), patient population (e.g. primary colorectal cancer patients, those with recurrent colorectal cancer or non-colorectal cancer) and anatomical location of stent. 12 SECTION 2 METHODS

29 - ASERNIP-S REVIEW OF SELF-EXPANDING METALLIC STENTS AUGUST Studies Included in the Review Designation of Levels of Evidence and Critical Appraisal The evidence presented in the included studies was classified according to the National Health and Medical Research Council (NHMRC) Hierarchy of Evidence (see Appendix A). Study quality was assessed according to the methods given in Chapter 6 of the Cochrane Reviewers Handbook (Higgins & Green 2005) and the CONSORT statement (Moher et al. 2001) on a number of parameters, such as the quality of the reporting of the study methodology, methods of randomisation and allocation concealment (for RCT s), attempts made to minimise bias, sample sizes and applicability of results outside the study sample, as well as examining the statistical methods used to describe and evaluate the study data. The included studies are shown in Table 3, Table 4 and Table 5. Several authors have published numerous reports on their experiences with self-expanding metal stents (SEMS). As a result, there are some studies published where there are very likely to be common pools of patients. All efforts have been made to avoid including duplicated data in this review and when the studies have reported the same outcome, the most recent study, or the study with the largest sample size, has been used. Description of Studies Self-expanding metal stents compared with surgery Nine studies compared SEMS with surgery; two randomised controlled trials, two comparative studies with concurrent controls and five comparative studies with historical controls. It was judged that meta-analysis or statistical pooling of these studies was not appropriate. The reporting of methodology in the randomised controlled trials was inadequate. Fiori et al. (2004) randomised patients into treatment groups using random number tables, but there were no details on allocation concealment or blinding. There was no explanation of the determination of sample size or participant flow through the trial, and statistical methodology was not adequately outlined and did not define if the analysis was by intention-to-treat. Losses to follow up were not stated and the duration of follow up was limited to 10 days. Xinopoulos et al. (2004) reported a double-blind trial in which participants were allocated to a treatment group on a 1:1 ratio, but provided no details of allocation concealment, methodology of blinding or randomisation implementation. There was no explanation of how the sample size was determined and it was not stated if analysis was by intention-to-treat. SECTION 3 INCLUDED STUDIES 13

30 - ASERNIP-S REVIEW OF SELF-EXPANDING METALLIC STENTS AUGUST The two comparative studies with concurrent controls also reported some methodological details insufficiently. Law et al. (2003) clearly stated the eligibility criteria for each treatment group, had treatment and comparator groups with similar baseline characteristics and explained the statistical methods used to compare the groups. The results were also well described in both narrative and tabular form, with the underlying cancer type explicitly stated. However, the primary outcomes were not well defined and participant flow through the study was not addressed, nor was the duration of follow-up or any losses to follow up. The study by Tomiki et al. (2004) reported the eligibility criteria for each group, explained the statistical analysis, defined the primary outcomes and presented a clear summary of the results. Follow up was also thoroughly reported with no losses. However, the comparator groups differed in baseline characteristics in regards to the location of the obstruction, which lowered the validity of the comparison. The methodological quality of two of the five comparative studies with historical controls could not be evaluated as one (Ramesh et al. 1999) was an abstract only and the other (Baqué et al. 2004) was published in French. Carne et al. (2004) reported a very thorough study with good methodological detail, although did not report outcomes stratified by cancer type. The other two studies (Johnson et al and Osman et al. 1999) both reported methodology in insufficient detail, particularly in regard to patient flow through the study. Also, the baseline characteristics of the comparator groups in Johnson et al. (2004) may not have been similar enough to warrant a valid comparison. Self expanding metal stents and elective surgery compared to emergency surgery Only one Level III-2 study addressed the comparison of self expanding metal stents followed by elective surgery and emergency surgery without prior stenting (Martinez- Santos et al. 2002). This study reported an intention-to-treat analysis, but did not clearly define details of patient allocation or inclusion and exclusion criteria. There were two retrospective comparative studies (Saida et al and Repici et al. 2004) that also reported on this comparision. The methodological quality of Repici et al. (2004) could not be adequately determined as it was published as an abstract only. Saida et al. (2003) did not describe their methodology adequately to determine the quality of the study a description of the patient allocation, primary objectives and participant flow were lacking. Covered self expanding metal stents compared to uncovered self expanding metal stents Two studies (Kang et al. 2002; Lee et al. 2003) directly addressed comparison between covered and uncovered stents. Kang et al. (2002) reported that the patients were randomly selected to receive one of three different stent types, but did not provide 14 SECTION 3 INCLUDED STUDIES

31 - ASERNIP-S REVIEW OF SELF-EXPANDING METALLIC STENTS AUGUST details of the randomisation process. The baseline characteristics of the groups were generally comparable, although the sizes of the comparator groups varied significantly. However, the outcomes were well reported and interpreted, taking into account the limitations of the study. The methodological quality of Lee et al. (2003) could not be assessed as it was published only in abstract form. Table 3. Summary of included comparative studies Study Device Level Study dates Indication n= SEMS versus elective surgery Fiori Precision stent 2004 system SEMS versus emergency surgery Law Wallstent 2003 (enteral or oesophageal) Tomiki 2004 Baqué 2004 (French) Osman 1999 Boorman 1999 Soonawalla 1998 II Jan 2001 May 2003 Palliation SEMS: 11 Open surgery: 11 III-2 Nov 1997 Jun 2002 Palliation SEMS: 30 Surgery: 31 Ultraflex III-2/3 Jan 1996 Dec 2002 Palliation SEMS: 18 Surgery: 17 Could not be III Jun 2001 Palliation determined Jan or bridge- SEMS: 16 Emergency surgery: 17 SEMS: 16 Surgery: 10 SEMS versus unspecified surgery Xinopoulos* 2004/2004 Wallstent II Mar 1998 Apr 2002 Palliation SEMS: 15 Colostomy: 15 Carne Wallstent III-3 Dec 1997 Sept 2002 Palliation SEMS: (enteral) Jan 1997 Aug 2002 Surgery: 19 Johnson Memotherm or III-3 Palliation SEMS: Wallstent Surgery: 18 Ramesh Wallstent or III-3 Palliation SEMS: Enteral stent Surgery: not stated (abstract only) to-surgery Wallstent III-3 Apr 1997 Apr 1998 Palliation or bridgeto-surgery SEMS + elective surgery versus emergency surgery Martinez- Wallstent or Santos Memotherm 2002 Repici 2004 (abstract only) Saida 1996/ /2004 III-2 Feb 1994 Nov 1999 Palliation or bridgeto-surgery Stainless steel Z-stent (Cook Co.) Covered SEMS versus uncovered SEMS Kang Covered vs 2002 uncovered Lee 2003 (abstract only) Niti-S stents (covered vs uncovered) SEMS versus SEMS + drug infusion Mao Wallstent or 2001 Memotherm III III-3 Mar 1999 Dec 2000 Bridge-tosurgery Bridge-tosurgery II/III-2 May 1999 July 2000 Palliation or bridgeto-surgery III-2/3 Palliation or bridgeto-surgery SEMS & surgery: 43 Emergency surgery: 29 SEMS: 28 Emergency surgery: 25 Elective surgery: 24 SEMS & surgery: 50 Emergency surgery: 40 Covered: 13 Uncovered: 8 Plus 6 covered not randomly allocated Covered: 37 Uncovered: 27 III-2 Oct 1996 May 2000 Palliation SEMS: 9 SEMS & drugs:19 (30 stents) *First 11 patients of SEMS group reported by Xinopoulos et al. 2002; Patients in SEMS group are part of a larger series reported in Law et al. 2004; Probable patient overlap with Lee et al & Kim et al Duration of follow-up SEMS: 4 days Surgery: 10 days Up to 26 months Up to 6 months 2 months At least 4 months 6 months 36 months Up to 85 months 2.1 months At least 7 days 8 months SECTION 3 INCLUDED STUDIES 15

32 - ASERNIP-S REVIEW OF SELF-EXPANDING METALLIC STENTS AUGUST Case series A detailed analysis of the methodological quality of the 73 included case series was not undertaken. The length of follow up in twenty of these reports was not stated or could not be determined and losses to follow up were rarely addressed. Seventeen of the case series reported outcomes separately for different types of cancer and fiftytwo reported at least some outcomes separately for patients treated with stents for palliation or as a bridge-to-surgery. Table 4. Summary of included case series Study Device Level Study dates n= Duration of patients stents follow up SEMS for palliation Araki Ultraflex IV Apr 1995 Mar months 2002 (uncovered) Arnell Wallstent IV Ben Soussan Choostent or IV Dec 1997 Jun months 2001 (French) Wallstent or Memotherm Buchanan Wallstent IV Jun 1995 Feb months 2000 Chevallier 2002 (French) Clark 2003 Coco 2000 Davies 2005 Dohmoto 1997 Fernández Lobato 1999 Gukovsky- Reicher 2003 Hünerbein 2005 Law 2004 Law 2000 Maetani 2004 Mishima 1999 Miyayama 2000 Wallstent or Choostent IV Jan 1999 Oct Up to 14.5 months Memotherm IV Feb 1999 Sept months Endocoil IV 3 3 Up to 12 months Bard Memotherm IV May 2000 Apr Up to 30 months Ultraflex or IV Up to 7 months Endocoil Wallstent IV Jul 1994 Mar Up to 40 months Wallstent (enteral) or Memotherm or Ultraflex (covered oesophageal) Ultraflex (uncovered) or Choostent or other Wallstent (uncovered oesophageal or enteral) or Ultraflex or Choostent Ultraflex or Wallstent Gianturco Z-stents or Nitinol stent Ultraflex (oesophageal) IV Up to 7 months IV months IV Nov 1997 Aug IV Jun 1997 Mar months IV 4 7 Up to 13 months IV Oct 1997 Feb over page 16 SECTION 3 INCLUDED STUDIES

33 - ASERNIP-S REVIEW OF SELF-EXPANDING METALLIC STENTS AUGUST Table 4. Summary of included case series continued Study Device Level Dates of study SEMS for palliation continued Osaka 2000 (Japanese) Paul Diaz Pothuri 2004 Repici 2000 Rey 1995 Ultraflex IV Could not be determined Wallstent (oesophageal) n= patients stents Duration of follow up 7 7 Could not be determined IV Apr 1994 Feb Up to 38 months Wallstent (enteral) or Gianturco Z-stent IV Aug 2001 Jan Ultraflex IV Jun 1997 Jan months (oesophageal) Wallstent or IV Nov 1992 Jul Up to 18 months Boston Scientific metallic prostheses Wallstent or IV Up to 16 months Streker stent IV Up to 4 months Rupp 1995 Sarela 2001 Scurtu Memotherm or IV Nov 2000 Nov months 2003 Wallstent (French) Shim Niti-S stent IV 7 7 At least 6 weeks 2004 Spinelli Cook Stainless IV Nov 1990 Feb months 2001 Steel Syn Wallstents IV Mar 2000 Aug (enteral (abstract only) uncovered) Tack Nitinol IV At least (uncoated) months Takahashi Wallstent IV (abstract only) Tsurumaru Could not be IV Could not be 8 8 Could not be 2004 determined determined determined (Japanese) Vanstiphout Wallstent IV 6 6 Up to (enteral) months (abstract only) SEMS as a bridge-to-surgery Balague Wallstent IV Mar 2002 Mar Up to 14 days 2004 De Gregorio Wallstent IV Up to 9 months 1996 (Spanish) Knopfle 2001 Knopfle 1998 (German) Lamah 1998 Mainar** 1996 Morino 2002 Wallstent or Sinusstent Wallstent (oesophageal) Wallstent or Cook Z-stent Wallstent (enteral) IV Jan 1996 May Could not be determined IV 6 6 IV At least 13 months IV Mar 2001 Apr Up to 8 months over page SECTION 3 INCLUDED STUDIES 17