Definition of large bowel obstruction by primary colorectal cancer: A systematic review

Abstract Aim Controversies on therapeutic strategy for large bowel obstruction by primary colorectal cancer mainly concern acute conditions, being essentially different from subacute obstruction. Clearly defining acute obstruction is important for design and interpretation of studies as well as for guidelines and daily practice. This systematic review aimed to evaluate definitions of obstruction by colorectal cancer in prospective studies. Method A systematic search was performed in PubMed, Embase and the Cochrane Library. Eligibility criteria included randomized or prospective observational design, publication between 2000 and 2019, and the inclusion of patients with an obstruction caused by colorectal cancer. Provided definitions of obstruction were extracted with assessment of common elements. Results A total of 16 randomized controlled trials (RCTs) and 99 prospective observational studies were included. Obstruction was specified as acute in 28 studies, complete/emergency in five, (sub)acute or similar terms in four and unspecified in 78. Five of 16 RCTs (31%) and 37 of 99 cohort studies (37%) provided a definition. The definitions included any combination of clinical symptoms, physical signs, endoscopic features and radiological imaging findings in 25 studies. The definition was only based on clinical symptoms in 11 and radiological imaging in six studies. Definitions included a radiological component in 100% of evaluable RCTs (5/5) vs. 54% of prospective observational studies (20/37, P = 0.07). Conclusion In this systematic review, the majority of prospective studies did not define obstruction by colorectal cancer and its urgency, whereas provided definitions varied hugely. Radiological confirmation seems to be an essential component in defining acute obstruction.

conservative treatment including laxatives with subsequent surgery in a semi-elective setting.
Clinical presentation of large bowel obstruction by primary colorectal cancer varies hugely in daily practice. Patients may present mainly with abdominal pain for several weeks, whereas others rapidly develop abdominal distention and might experience disproportionately mild symptoms. Conflicting results have been published regarding the degree of colorectal obstruction and SEMS success rates [2], which might be explained by variation in clinical presentation. Recently, a scoring system was developed by a Japanese group (the ColoRectal Obstruction Scoring System, CROSS) in order to evaluate the degree of colorectal obstruction and consequently aid in the choice of treatment of patients with obstructive colorectal cancer [3]. In their most recent guideline, the European Society of Gastrointestinal Endoscopy (ESGE) recommends against prophylactic SEMS placement in patients with a subacute obstruction [2], but without providing a clear definition.
A clear definition of obstruction by colorectal cancer might reduce overtreatment of patients with mild conditions, and focuses the need for emergency treatment towards patients with an acute presentation. In addition, literature on patients with obstructive colorectal cancer can be compared more effectively with more appropriate translation into clinical guidelines and daily practice. Furthermore, it enables clinical benchmarking. Therefore, the aim of this systematic review was to provide a literature overview of used definitions of obstruction by colorectal cancer in prospective studies, thereby serving as a basis for the development of a consensus definition.

ME THODS
This systematic review was reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines [4]. No review protocol was registered.

Inclusion/exclusion criteria
Studies were included in the case of a randomized or prospective observational study design, a publication date between 1 January

Study selection
The literature search yielded a total of 6797 articles (  Table 1.

Clinical symptoms
The most frequently reported clinical symptoms included abdominal pain, inability to pass stool or flatus, nausea and/or vomiting. The CROSS score, which focuses on the level of oral intake along with symptoms of stricture, was used in two of 42 studies (4.8%) [12,43].
In three of the studies [11,43,44], absence of flatus determined the degree of obstruction: if the patient was still able to pass flatus, the obstruction was incomplete. The required duration of symptoms for patients to be eligible for inclusion was reported in eight studies [8,23,25,28,29,34,38,41] The new nitinol conformable self-expandable metal stents for malignant colonic obstruction: a pilot experience as bridge to surgery treatment.

Kamocki 2014
Own experiences of endoscopic self-expandable stent placement for malignant colorectal ileus.

Kim 2014
Mmp-9 expression after metallic stent placement in patients with colorectal cancer: association with in-stent restenosis.

Kim 2014
Preoperative colonoscopy through the colonic stent in patients with colorectal cancer obstruction.

Krstic 2014
Hartmann's procedure vs loop colostomy in the treatment of obstructive rectosigmoid cancer.

Lo 2014
Protocol-driven self-expanding metallic stenting for malignant large-bowel obstruction in a district hospital Occhionorelli 2014 Colonic stent placement as a bridge to surgery in patients with left-sided malignant large bowel obstruction. An observational study.

Ding 2013
A temporary self-expanding metallic stent for malignant colorectal obstruction.

Ghazal 2013
Colonic endolumenal stenting devices and elective surgery versus emergency subtotal/total colectomy in the management of malignant obstructed left colon carcinoma.

Lamazza 2013
A new technique for placement of a self-expanding metallic stent (SEMS) in patients with colon rectal obstruction: a prospective study of 43 patients.

Lee 2013
Novel method of stent insertion for malignant lower rectal obstruction with proximal releasing delivery system (with video).

Lim 2013
Preoperative colonoscopy for detection of synchronous neoplasms after insertion of self-expandable metal stents in occlusive colorectal cancer: comparison of covered and uncovered stents. Colorectal stenting as a bridge to surgery reduces morbidity and mortality in left-sided malignant obstruction: a predictive risk score-based comparative study.

Chen 2012
Laparoscopic management for acute malignant colonic obstruction.

Cheung 2012
Outcome and safety of self-expandable metallic stents for malignant colon obstruction: a Korean multicenter randomized prospective study.

Chou 2012
Dual-design expandable colorectal stent for a malignant colorectal obstruction: preliminary prospective study using new 20-mm diameter stents.

Ho 2012
Endoscopic stenting and elective surgery versus emergency surgery for left-sided malignant colonic obstruction: a prospective randomized trial.

JimenezFuertes 2012
Resection and primary anastomosis without diverting ileostomy for left colon emergencies: is it a safe procedure?
Larssen 2012 Long-term outcome of palliative treatment with self-expanding metal stents for malignant obstructions of the GI tract.

2010
Quality of life and symptom control after stent placement or surgical palliation of malignant colorectal obstruction.

Park 2010
Comparison of efficacies between stents for malignant colorectal obstruction: a randomized, prospective study.

Tanaka 2010
Endoscopic balloon dilation for obstructive colorectal cancer: a basic study on morphologic and pathologic features associated with perforation.

2009
Elective (planned) colectomy in patients with colorectal obstruction after placement of a self-expanding metallic stent as a bridge to surgery: the results of a prospective study.

2009
Endolaparoscopic approach vs conventional open surgery in the treatment of obstructing left-sided colon cancer: a randomized controlled trial. Kim

2009
Dual-design expandable colorectal stent for malignant colorectal obstruction: comparison of flared ends and bent ends.

2009
Use of modified multidetector CT colonography for the evaluation of acute and subacute colon obstruction caused by colorectal cancer: a feasibility study.

2009
Clinical utility of serum tumor markers in the diagnosis of malignant intestinal occlusion. A prospective observational study.

2009
Colorectal stenting for management of acute malignant bowel obstruction in advanced colorectal cancer in Iran.

2009
Self expanding wall stents in malignant colorectal cancer: is complete obstruction a contraindication to stent placement? Baraza 2008 Combination endo-radiological colorectal stenting: a prospective 5-year clinical evaluation.

Elsberger 2008
Self-expanding metallic stent insertion in the proximal colon Colorectal stenting as an effective therapy for preoperative and palliative treatment of large bowel obstruction: 9 years' experience.

Choi 2007
Interventional management of malignant colorectal obstruction: use of covered and uncovered stents.

Lee 2007
Comparison of uncovered stent with covered stent for treatment of malignant colorectal obstruction.

Mitchell 2007
Emergency room presentation of colorectal cancer: a consecutive cohort study. Mucci-Hennekinne

2007
Management of acute malignant large-bowel obstruction with self-expanding metal stent. Olmi

Repici 2007
Ultraflex precision colonic stent placement for palliation of malignant colonic obstruction: a prospective multicenter study.

Song 2007
A dual-design expandable colorectal stent for malignant colorectal obstruction: results of a multicenter study.

Tsurumaru 2007
Self-expandable metallic stents as palliative treatment for malignant colorectal obstruction.

McArdle 2006
The impact of blood loss, obstruction and perforation on survival in patients undergoing curative resection for colon cancer.

Physical examination
Findings during physical examination that were included in defini-

Endoscopic features
Endoscopic features were included in the definition of obstruction in six studies and were described as 'the inability of the endoscopist to visualize the proximal lumen' [43,44], 'a stenosis that could not be passed with a colonoscope' [33,46] or 'severe colonic obstruction on endoscopic imaging' [45]. One study specifically defined nearly complete obstruction using endoscopic features: 'complete colonoscopic examination was impossible because of narrowing' [26].

Radiological imaging
Descriptions S + E + R E + R R of obstruction, it seems necessary to further specify this condition.
Considering the desired relevance of the definition for therapeutic decision-making, one should name the condition that indicates the necessity for an emergency intervention, either surgical or endoscopic. 'Acute obstruction' probably best expresses this clinical scenario, while 'complete obstruction' wrongly implies that one can reliably assess the degree of obstruction by any measure. If urgency was specified, 'acute' was used in the vast majority of studies.
Clinical symptoms that were included in the definitions were abdominal pain, nausea, vomiting and several words and phrases referring to problems with passing stools or flatus. Reporting these symptoms may vary between physicians according to differences in education, specialization and experience, besides geographical and psychosocial differences in the way patients present their symptoms, and thus be subject to inter-observer variability. Some of the symptoms are relatively unspecific, such as abdominal pain and nausea. Vomiting is a more objective symptom, but only presents in the case of malignant obstruction if the small bowel dilates with insufficiency of the ileocaecal valve. Inability to pass stools or flatus might also be difficult to judge, and terms such as 'constipation', 'change in bowel habits' or 'difficulty in defaecation' do not seem to be appropriate to define acute obstruction.
Duration of symptoms was infrequently described and varied be- In the case of emergency surgery, colonoscopy is often not performed before resection or construction of a decompressing stoma. This was confirmed by the current systematic review, in which endoscopic characteristics were infrequently part of the requirements for having obstructive colorectal cancer. Furthermore, endoscopic features such as inability to pass the endoscope might be observed in the absence of any clinical or radiological signs of obstruction. For these reasons, endoscopic features should probably not be included in the definition of acute obstruction. In contrast, a CT scan showing dilated colon proximal to a malignant appearing stenosis is probably one of the most reliable elements of a definition of obstruction [47].
The only difficulty for radiologists is to distinguish obstruction from colonic dilatation or pseudo-obstruction, and a contrast enema can help to differentiate. Furthermore, the clinical diagnosis only fits into 'acute obstruction' in combination with at least one clinical criterion such as vomiting, distended abdomen or not passing stools or flatus for at least 48 h.
The required maximum interval between presentation and first intervention, reflecting urgency and severity of the obstruction, was reported even less frequently than duration of symptoms. In one RCT [29], patients had to be treated with either an SEMS or surgery within 24 h of randomization. Although such a criterion might add to the definition of acute obstruction, incorporating timing of subsequent therapeutic interventions is probably not the purest way of defining a clinical condition. Considering therapeutic consequences, it is also of relevance that the ESGE guideline of 2020 recommends against prophylactic colonic SEMS placement. According to the guideline, SEMS is only indicated in patients with both obstructive symptoms and radiological findings suspicious of malignant large bowel obstruction, because of the potential risks associated with colonic stenting [2]. An unclear distinction between acute and imminent obstruction may result in overtreatment of patients who might experience relief of mild symptoms by, for example, laxatives with subsequent semi-elective surgery. This underlines the need to talk about 'acute obstruction', as mentioned before.
Recently, a scoring system CROSS was developed by a Japanese group in order to evaluate the degree of colorectal obstruction and consequently aid in the choice of treatment of patients with obstructive colorectal cancer [3]. This scoring system focuses on the level of oral intake along with symptoms of stricture, including abdominal pain or cramps, abdominal distention, nausea, vomiting, constipation and diarrhoea. The less able a patient is to eat soft solids, the lower the CROSS score. However, this scoring system is infrequently used in the literature. This was confirmed by the current systematic review, with only two of 42 studies (4.8%) adhering to the CROSS scoring system. A disadvantage of this scoring system is the lack of any radiological criteria. Before widespread implementation, such a scoring system has to be assessed regarding its relevance to therapeutic decision-making and subsequent clinical outcome parameters. Subsequently, validation is required in different clinical settings.
The limitations of the present review are related to the selection of studies. Besides RCTs, we decided to include studies with a prospective study design. However, the term 'prospective' does not necessarily mean that a complete research protocol had been written before data collection and might only indicate that patients were prospectively identified. This might explain the low proportion of definitions provided, although the proportion was similar for RCTs. In addition, because of the rather long inclusion period, the methodological criteria of designing and reporting prospective studies as well as the diagnostic work-up of such patients have probably changed over time. Furthermore, insight into the clinical relevance of the urgency of the obstruction might have increased.
In conclusion, obstruction by colorectal cancer was not clearly defined and its urgency was not specified in the majority of the included prospective studies in the current systematic review.
Radiological imaging showing distended bowel proximal to a suspicious malignant stenosis seems an essential element of a definition of obstruction by colorectal cancer. If combined with a distended abdomen during physical examination with or without specific clinical symptoms, this can define the clinical condition of 'acute obstruction' with required relevance for therapeutic decision-making.
Consensus on one uniform definition is warranted, in order to reduce overtreatment of imminent obstruction, to improve comparability of the literature, to facilitate guideline development and to enable benchmarking within a clinical audit.

DATA AVA I L A B I L I T Y S TAT E M E N T
The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.

FU N D I N G I N FO R M ATI O N
This research did not receive any specific grant from funding agencies in the public, commercial or not-for-profit sectors.