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- Materials and methods
A variety of surgical treatments and medical therapies are recommended for dogs with extrahepatic congenital portosystemic shunts (CPSS). The objective of this review was to assess the evidence base for the management of extrahepatic CPSS in dogs. An online bibliographic search was performed in November 2010 to identify articles relating to the question “Which of the treatment options for extrahepatic CPSS in dogs offers the best short- and long-term outcomes?” Articles were assigned a level of evidence based on a modified grading system. Thirty-eight articles were included in the review. Thirty-six articles were classified as grade 4 and two as grade 5. The timings and methods of assessment of short- and long-term outcomes varied widely between studies. One prospective study (grade 4a) showed that surgically treated dogs survived significantly longer than medically treated dogs. Four retrospective studies (grade 4b) compared the outcome of two surgical techniques but there were no statistically significant differences between treatment groups in terms of complications or outcome. The review found that the evidence base for the treatment of extrahepatic CPSS is weak. There is a lack of evidence of short- and long-term outcomes to recommend one treatment over another.
Materials and methods
- Top of page
- Materials and methods
To establish the evidence base for the treatment of extrahepatic CPSS in dogs, the following question was composed:
“Which of the treatment options for extrahepatic CPSS in dogs offers the best short- and long-term outcomes?”An online bibliographic search was performed in November 2010 for articles relating to the treatment of extrahepatic CPSS in dogs. The search utilised the PubMed (http://www.pubmed.gov/), ISI Web of Science (http://wok.mimas.ac.uk/) and CAB direct (http://www.cabdirect.org/) databases. Databases were searched using the following terms: (portosystemic shunt OR portocaval shunt OR portovascular anomaly OR portosystemic communication OR extrahepatic vascular anomaly) AND (dog OR canine OR case) AND (treatment OR outcome OR mortality OR morbidity OR complications).
Analysis was restricted to the English language veterinary literature reporting information on the treatment of extrahepatic CPSS in dogs. The abstracts were reviewed for relevance to the question. Articles were excluded if they were experimental studies, described only acquired PSS or intrahepatic CPSS, were case reports or small case series (less than nine dogs) or did not provide any detail regarding outcome (e.g. articles describing diagnostic tests, and so on).
Articles that fitted these criteria were reviewed by the primary author and were assigned a level of evidence based on a modification of a grading system published by the Oxford Centre for Evidence-Based Medicine (Table 1). This grading system was simplified to remove some categories which did not readily apply to the available veterinary literature. In addition, Level 4 evidence was further sub-divided to enable greater differentiation among the evidence currently available. This allowed a distinction to be made between lower quality prospective cohort studies, retrospective cohort studies, case series specifically dealing with outcome, and other case series. As most of the articles fell into Level 4 evidence this enabled more detailed interpretation of the available evidence.
Table 1. Levels of evidence
|1a||Systematic review of randomised controlled trials (RCT)|
|1b||Individual RCT (with narrow confidence interval)|
|2a||Systematic review of cohort studies*|
|2b||Individual cohort study (including low quality RCT)|
|3a||Systematic review of case–control studies†|
|3b||Individual case–control study|
|4a||Lower quality prospective cohort/case–control study – concerns regarding definition of comparison groups and / or objective (preferably blinded) nature of assessment and /or consideration of confounding factors and / or adequacy of follow up|
|4b||Retrospective cohort/case–control study|
|4c||Case series – describing outcome for one treatment method with no control group|
|4d||Case series – describing novel aspect of management and providing some information regarding outcome|
|4e||Lower quality case series – concerns regarding study design and/or ability to interpret information|
|5||Expert opinion without explicit critical appraisal, or based on physiology, bench research or “first principles”|
The following data was recorded from each article: the type of study described (such as case series, cohort study, etc.); the size of the study population; the treatment used; the peri-operative complication and mortality rate (short-term outcome); details of long-term outcome including duration of follow-up and method of assessment. It was anticipated that the nature of the outcomes reported would vary between articles, in particular the nature and duration of long-term outcomes. Therefore, the way in which outcome was assessed, the timings and the result was recorded for each article.
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- Materials and methods
This review found that the evidence base for the treatment of extrahepatic CPSS is very weak. No grade 1, 2 or 3 studies were identified which is unfortunate as these provide the best information for clinicians to make an informed choice regarding treatment. Most of the studies included in this review were retrospective cohort studies or retrospective case series and were graded 4 or below. Thus there is a lack of good evidence to support the use of one treatment over another.
The articles included in this study cover a long time period from 1987 to 2010. The most recent studies comparing two surgical treatments were published in 2003 (Hurn and Edwards 2003, Winkler and others 2003). Only one large case series of cellophane banding and one large case series of ameroid constrictors have been published to date (Hunt and others 2004, Mehl and others 2005). There has been a shift away from reporting studies specifically investigating outcome over the last five years. This could suggest that authors believe that sufficient evidence has been gathered in the existing literature to allow distinction between treatment options. The strength of any study which compares two treatments is dependent on whether patients were randomly allocated to treatment groups, whether the assessors were blinded, whether the treatment groups were similar, whether the follow-up was sufficient and whether groups were managed equally apart from the treatment. Therefore, when attempting to choose between treatments for CPSS ideally the decision would be based on evidence from prospective randomised controlled trials, comparing two or more treatments. Unfortunately such trials do not exist; decision making relies on prospective or retrospective cohort studies or case series. This review highlights that there is actually still a need for randomised prospective cohort studies comparing treatment options. Unfortunately, randomised prospective studies are not easily achieved. Issues of time, cost, case recruitment/numbers and owner/clinician compliance are all significant but not insurmountable obstacles.
This review identified a wide variation in how outcome for CPSS treatment is assessed and this represents a significant obstacle both to the comparison of existing articles and for the planning of new studies. Possible outcome measures for CPSS include short-term information such as peri-operative complications and mortality and long-term data focusing on recurrence of clinical signs, quality of life (QOL) and survival. This review found very little consistency between articles not only in the method used to assess outcome but also in the time periods concerned. There was wide variation between the time period that articles used to describe peri or postoperative mortality, ranging from days to weeks or not being specified (Hottinger and others 1995, Winkler and others 2003, Hunt and others 2004, Kummeling and others 2004). Long-term follow-up varies considerably between articles, both in duration and also in methods of assessment, i.e. clinical assessment, biochemical testing, ultrasonography, scintigraphy. The lack of consistency between studies makes direct comparison unhelpful. In order to allow fair comparisons, ideally all studies would use the same validated outcome measure. The inconsistency in length of follow-up may be particularly significant in dogs with CPSS as treatment is typically performed very early in their life. In addition some studies have shown that recurrence of clinical signs can occur three to six years after seemingly successful surgery (Mathews and Gofton 1988, Hottinger and others 1995, Komtebedde and others 1995, Kummeling and others 2004). Thus a long and consistent follow-up period is essential to identify any differences between treatments.
Short-term complications and mortality are important and relatively easy to quantify. Long-term outcome remains much more difficult to assess. Long-term outcome is also more difficult to obtain as it requires that the clinician maintain contact with the owner and the dog over time. Objective outcome measures include ammonia tolerance testing, dynamic bile acid testing, ultrasound, scintigraphy, contrast computed tomography and magnetic resonance imaging. These methods provide specific information, particularly on the presence of persistent or recurrent shunting. However, there is little information which can be used to relate these findings to the final outcome for the individual with some dogs having apparently good clinical outcomes with persistent shunting and many papers reporting persistently increased bile acids or continued shunting on scintigraphy in dogs that have made good recoveries (Komtebedde and others 1995, Hunt and Hughes 1999, Mehl and others 2005). A validated quality of life assessment index would be a useful additional tool to enable clinicians to determine a patient focussed outcome which may be more useful than a technically focused one. Such tools have been developed for other canine conditions including cardiac disease, chronic pain, spinal cord injury and cancer pain (Freeman and others 2005, Yazbek and Fantoni 2005, Wiseman-Orr and others 2006, Levine and others 2008). Use of a consistent outcome measure for CPSS would facilitate comparison between papers and techniques.
When considering management options for dogs with extrahepatic CPSSs ideally the treatment with the best short-term (mortality rate) and long-term outcomes would be selected. The review identified five articles which directly compared two treatment options and were considered to provide reasonable evidence. The paper by Greenhalgh and others (2010) provides the strongest evidence available and reports a reasonable number of dogs. This evidence would support the use of surgical management over medical treatment although it is still weak (grade 4a). Three grade 4b papers compared the outcomes between suture ligation and ameroid constrictor placement. This evidence is weak and based on small numbers; however, this is the most robust evidence that is available for choosing between surgical treatment options. Although these articles did identify differences in several different outcome measures between dogs treated with suture attenuation and ameroid constrictors these were not statistically significant. These studies included relatively small numbers of dogs in each group. It is entirely possible that there is a difference in terms of complications between the two treatments but there were insufficient numbers to detect it (a type II error). Differences between the treatment groups may be relatively small. In such instances the sample size required to detect a statistically significant difference is relatively large, which may be challenging to achieve in clinical veterinary research. When planning a study, a power calculation should be used to assess the number of participants required to detect a specified difference between groups and thereby ensure that worthwhile studies are undertaken. Consideration of this calculation should be included in the materials and methods of a study. None of the studies reviewed in this article reported having performed such a calculation. Two studies did report that ameroid constrictor placement was statistically significantly faster than suture attenuation. However, the importance or significance of this has not been investigated further although this may suggest that ameroid constrictor placement is easier and possibly cheaper. It can be concluded that there is not sufficient evidence to recommend the use of suture ligation over ameroid constrictor placement and vice versa on the basis of outcome. One grade 4b study compared the incidence of neurological complications between dogs treated with suture attenuation and cellophane banding. This found no significant difference between the two treatments but only focused on one aspect of outcome. No studies have compared ameroid constrictor placement with cellophane banding.
The majority of articles in this review were case series with no comparison or control group and thus provide weak evidence. Whilst these studies can justify the use of a given technique they do not provide evidence for whether one treatment is superior to another. Although the mortality rate is greater for some of the suture attenuation papers compared with the ameroid or cellophane band studies, for some the mortality rates are very similar. It is unknown whether any apparent differences in outcome are a direct result of the technique, are due to other factors or are a result of chance. Surgery is highly operator dependent and there can be a steep learning curve associated with a given technique. These factors should be taken into account when interpreting evidence because a given technique may not have the same results at a different institution. These case series also span a long time period (from 1987 to 2008). Other factors such as anaesthetic and postoperative care and greater familiarity with case management may have affected the results during this time period although this remains unproven. Whilst the evidence does not support the use of one technique over another based on outcome, there may be other compelling and valid reasons to use one option in a given situation, such as financial considerations, clinician familiarity or treatment availability.
A subjective grading system was used to categorise the articles included in this review. It is important to note that this grading system is not precise and some readers may disagree with the results. However, allowing for differences in opinion regarding the precise grade of the articles included, the overall results of this review would still be the same; all of the evidence would fall within grades 4 and 5. The articles were graded according to their evidence base related to outcome. Some articles provide a higher or lower level of evidence for another aspect of CPSS management. The grading process is not a criticism of specific articles. All of the articles included in this review contain important or useful information and make a valuable contribution to the literature on CPSS.
The review did not include any articles describing the use of intravascular occlusion techniques. This was unfortunate as intravascular treatments are likely to become more common place in the future, particularly for intrahepatic shunts. Several small case series have described the use of intravascular coils in dogs with extrahepatic CPSS but these did not include sufficient cases to meet the inclusion criteria (Leveille and others 2003, Bussadori and others 2008, Hogan and others 2010).
The veterinary profession should continue to strive to adopt an evidence-based approach in order to optimise patient care. It is clear that for the treatment of extrahepatic CPSS (as in many other areas of veterinary medicine) there is a lack of convincing evidence to recommend any one treatment over another. Therefore veterinary surgeons should integrate the existing knowledge with clinical experience and the needs of the animal to recommend the best treatment. In practice this means that clinicians should continue to use the technique that they are most comfortable with. However, veterinary surgeons should endeavour to improve the quality of research and hence the evidence base available. There are still many unanswered questions regarding the management of dogs with CPSS. Large randomised prospective studies are needed to compare existing and new treatments in order to determine which are associated with the best outcome for dogs. Further investigation is also needed into developing consistent and validated outcome measures, possibly including a validated quality of life assessment tool.
The authors are very grateful to the Kennel Club Charitable Trust who generously provided a grant to support MST’s PhD studies.
Conflict of interest
None of the authors of this article has a financial or personal relationship with other people or organisations that could inappropriately influence or bias the content of the paper.