Clinical outcomes and risk factors of post-polypectomy coagulation syndrome: a multicenter, retrospective, case–control study

• Introduction
• Patients and methods
• Study design
• Colonoscopic polypectomy
• Definition of PPCS
• Statistical analysis
• Results
• Discussion
• References

Background and study aims: Post-polypectomy coagulation syndrome (PPCS) is a well known complication of colonoscopic polypectomy. However, no previous studies have reported on the clinical outcomes or risk factors of PPCS. The aim of the current study was to analyze the clinical outcomes and risk factors of PPCS developing after a colonoscopic polypectomy.

Patients and methods: Data for all patients who underwent colonoscopic polypectomies and required hospitalization in nine university hospitals were analyzed retrospectively. The incidence, clinicopathological characteristics, and clinical outcomes of PPCS cases were examined. Additionally, patients who developed PPCS were compared with controls who were matched by age and sex, in order to assess for possible risk factors.

Results: The rate of PPCS that required hospitalization after colonoscopic polypectomy was 0.7/1000. All patients with PPCS were treated medically without the need for surgical interventions. The median durations of therapeutic fasting, hospitalization, and antibiotic use were 3 days, 5.5 days, and 7 days, respectively. The rates of major PPCS and mortality were 2.9 % and 0 %, respectively. On multivariate analysis, hypertension (OR = 3.023, 95 %CI 1.034 – 8.832), large lesion size (OR = 2.855, 95 %CI 1.027 – 7.937), and non-polypoid configuration (OR = 3.332, 95 %CI 1.029 – 10.791) were found to be independent risk factors related to the development of PPCS. 

Conclusions: In this study, the rates of major PPCS and mortality were only 2.9 % and 0 %, respectively. Hypertension, large lesion size, and non-polypoid configuration of the lesion were independently associated with PPCS. Therefore, patients may be reassured by the excellent prognosis of PPCS, while endoscopists should be especially careful when performing colonoscopic polypectomies in patients with hypertension or large and non-polypoid lesions.

Introduction

Colorectal cancer (CRC) develops in an adenoma – carcinoma sequence. Colonoscopic polypectomy has been shown to reduce the incidence of CRC by 70 % – 80 % [1]. Colonoscopic polypectomy is a relatively safe procedure [2] [3] [4] [5] [6], yet there is the possibility of serious complications such as perforation, bleeding, and post-polypectomy coagulation syndrome (PPCS) [7] [8] [9] [10] [11]. Previous studies on the complications of colonoscopic polypectomy have focused primarily on perforation or bleeding [7] [8] [9], and not specifically on PPCS. 

PPCS, also known as post-polypectomy syndrome or transmural burn syndrome, refers to the development of abdominal pain, fever, leukocytosis, and peritoneal inflammation in the absence of frank perforation that occurs after colonoscopic polypectomy with electrocoagulation [12] [13] [14] [15] [16]. Recognition of PPCS is important in order to avoid unnecessary exploratory laparotomy, as the syndrome has been shown to resolve with conservative treatment in the majority of patients. However, little is known about the actual clinical characteristics, clinical outcomes, and risk factors associated with PPCS. Although relatively low, the incidence of PPCS has the potential to become a significant public health problem given the large and increasing number of colonoscopic polypectomies performed every year.

The current study analyzed the clinicopathological characteristics, clinical outcomes, and risk factors of PPCS. To the best of our knowledge, this is the first study in the English literature to evaluate the clinicopathological characteristics, clinical outcomes, and risk factors of PPCS. 

Patients and methods

Study design

This study evaluated consecutive patients who developed PPCS after colonoscopic polypectomies at nine university hospitals in the Republic of Korea between June 2006 and June 2011. In order to identify cases of PPCS, all medical records were reviewed for patients who required hospitalization and abdominal computed tomography (CT) examination associated with colonoscopic polypectomies during the study period. One physician at each hospital was responsible for data collection, and the completeness of the data collection was monitored by one of the authors (J.M.C.). Patients with inflammatory bowel diseases, familial adenomatous polyposis, or non-epithelial neoplasms (such as carcinoid or lymphoma) were excluded. Patients were also excluded if they experienced complications of bleeding or perforation or if their polyps were removed only by biopsy forceps, by cold snare polypectomy or endoscopic submucosal dissection.

The following retrospective data were collected for each patient with PPCS: age, sex, alcohol consumption, smoking, co-morbid diseases, body mass index (BMI), laboratory data (including white blood cell count and C-reactive protein [CRP] level), clinical presentations, clinical outcomes, medical treatment (therapeutic fasting and intravenous antibiotics), endoscopic data (procedure time, number of polypectomies, submucosal injection, and the size, location, and shape of the lesions), and histopathology. Patients who underwent colonoscopic polypectomies without complications, which were performed within 1 month of each case with PPCS, were classified as the controls. Twice as many controls as cases were randomly selected from the remaining study cohort and matched with each case for age (± 2 years) and sex (2 : 1 matching).

The study was performed according to the principles of the Declaration of Helsinki, and was approved by the Institutional Review Board of each hospital.

Colonoscopic polypectomy

All participating endoscopists were experts who had previously performed more than 1000 polypectomies. Colonoscopic polypectomies were performed using Olympus endoscopes (CF-240I or CF-Q260AI; Olympus Optical, Tokyo, Japan) or Fujinon endoscopes (EC-590ZW/L; Fujinon Inc., Saitama, Japan) in all hospitals. An ERBE ICC 200 or VIO-300 D electrocautery device (ERBE Electromedizin, Tübingen, Germany) was used for electrosurgery. In general, the automatically controlled cutting mode (Endocut) was applied with the electrosurgical unit set at Effect 1 – 2 (output limit 50 – 60 W), and the total time of application of current ranged from about 1 to 5 seconds (depending on polyp size and features).

Bowel preparation was performed with polyethylene glycol electrolyte solution in all hospitals. Submucosal injection was selected according to the size and shape of each lesion. In general, small protruding lesions were resected without submucosal injection, whereas large protruding or broad-based lesions were removed after submucosal injection. Submucosal injection was commonly used for polyps greater than 10 mm in size and those located in the right colon. The epinephrine solution (a solution of epinephrine diluted 1/10 000 in saline) was injected until the mucosa was blanched and bulged, with a total of 2 – 10 mL of solution being injected to each lesion that required lifting.

The size of each polyp was classified based on the colonoscopic images and the colonoscopic records of the patients. The location of the polyps were categorized as either right colon (cecum, ascending colon, and transverse colon) or left colon (descending colon, sigmoid colon, and rectum). The macroscopic appearance was classified as either polypoid or non-polypoid configurations. Polypoid (0-Ip, 0-Is) lesions were defined as having a height more than half the diameter. Non-polypoid (0-II and laterally spreading tumor [LST]) lesions were defined by a height less than half the diameter [17] [18]. The number of adenomas was classified as either single or multiple (≥ 2).

Histopathological diagnosis was determined on excised specimens according to World Health Organization criteria [19]. Lesions were categorized based on their most advanced pathological features. The dysplasia of the adenoma was classified as low grade dysplasia (LGD) or high grade dysplasia (HGD). LGD included mild or moderate dysplasia, whereas HGD comprised severe dysplasia, carcinoma in situ, or intramucosal carcinoma [20] [21].

Possible complications of colonoscopic polypectomy were explained to all patients before the procedure, and written consent was obtained from each patient. If anticoagulant or antiplatelet agents (such as aspirin, ticlopidine or warfarin) had been prescribed, they were discontinued at least 7 days prior to the procedure. All patients who underwent polypectomy were advised to refrain from alcohol consumption and heavy exercise for 7 days after the procedure. Patients were informed to contact the endoscopy center or visit an emergency room if they experienced any symptoms or signs of post-procedural complications. Complications of polypectomies were confirmed in all patients at the end of the colonoscopic polypectomy and at the follow-up visit on 3 to 7 days after the procedure.

Definition of PPCS

Patients with possible PPCS were selected from patients who required hospitalization and abdominal CT examination following colonoscopic polypectomy. From these possible cases, patients with PPCS were diagnosed when they presented with abdominal pain, fever, leukocytosis, raised CRP or peritoneal irritation symptoms/signs that occurred after colonoscopic polypectomy with electrocoagulation, in the absence of visualized perforation by abdominal CT. Perforation was defined as either unequivocal observation of this complication during polypectomy or subsequent laparotomy or by the presence of free or retroperitoneal air on either plain abdominal radiography or CT.

A major PPCS was defined as a complication leading to shock, admission to the intensive care unit (ICU), additional surgery, or death. A minor PPCS was defined as a complication not resulting in one of the aforementioned conditions (i. e. PPCS managed by conservative management, without the need for ICU admission or additional surgery).

Statistical analysis

Results were expressed as mean ± SD or percentage. Continuous variables were compared between the two groups using the t test or the Mann – Whitney U test, as appropriate. Categorical variables were compared between the two groups using the chi-squared test or Fisher’s exact test. The odds ratio (OR) and 95 % confidence interval (CI) were computed using logistic regression analysis. Variables with P < 0.1 in the univariate analysis and well known risk factors associated with colonoscopic polypectomy (such as size, location, configuration, histopathology, number of polyps [7] [8] or the presence of hypertension [9]) were added to the multivariate logistic regression model to identify independent risk factors for PPCS. A two-tailed P value < 0.05 was considered to be statistically significant, and a P value < 0.1 was considered to be a statistical trend. Statistical analysis was performed using the Statistical Package for the Social Sciences (SPSS) version 13.0 for Windows (SPSS, Chicago, Illinois, USA).

Results

During the study period, a total of 47 083 consecutive patients underwent colonoscopic polypectomies at nine university hospitals in Korea. Among these patients, 34 patients with PPCS (0.07 %) were treated following hospitalization for their symptoms. The 34 patients included 15 men and 19 women, with a mean age of 61.5 ± 9.6 years (range 41 – 78 years). The time between colonoscopic polypectomy and the CT scan for diagnosis of PPCS was 0.53 ± 0.75 days (range 0 – 3 days), and therefore the possibility of non-visualization of free air after absorption of small amounts of air, which may lead to misinterpretation of a perforation case as a PPCS case, may be minimal.

[Table 1] shows the clinical characteristics and outcomes of the 34 patients with PPCS. Sensitivity for the detection of PPCS was 100 % for an abnormal CRP range and 58.8 % for leukocytosis. Abdominal pain and fever was found in 88.2 % and 64.7 %, respectively, of patients with PPCS. All patients with PPCS were treated medically without surgery. Only one patient (2.9 %) was classified as having a major PPCS due to ICU admission. The patient refused surgery and recovered after 63 days of hospitalization, which included 10 days of therapeutic fasting and 30 days of antibiotics. The median time frame of therapeutic fasting, hospitalization, and antibiotic use were 3 days, 5.5 days, and 7 days, respectively, in patients with PPCS. All of the patients recovered completely without sequelae and with a zero mortality rate.

[Table 2] shows the endoscopic and histopathological data of the 34 patients with PPCS. The mean total procedure time was 37.3 ± 15.0 minutes. The mean number of polypectomies was 3.1 ± 3.6, and submucosal saline injection was performed in 67.6 % of patients. The mean size of the largest lesion was 13.3 ± 6.8 mm, with 23 patients (67.6 %) having lesions larger than 10 mm. Lesions were predominantly (70.6 %) located in the right colon. With regard to the appearance of the lesions, 22 patients (64.7 %) had polypoid configurations and only one of them had a pedunculated configuration. The remaining 12 patients (35.3 %) had non-polypoid configurations, nine (75.0 %) of whom had LSTs. Most (70.6 %) of the lesions were adenomas with LGD or non-neoplastic histopathology. The other 29.4 % of the lesions were adenomas with HGD, which included intramucosal carcinoma (n = 3).

[Table 3] shows the case – control analysis for risk factors in patients with and without PPCS. Patients in the PPCS group had a greater frequency of larger lesions and non-polypoid configurations (P = 0.025 and P = 0.019, respectively). In addition, there was a trend toward greater frequency of hypertension in the PPCS group than in the non-PPCS group (P = 0.050). However, there were no significant differences between the groups with regard to age, sex, alcohol consumption, smoking, diabetes mellitus, BMI, total procedure time, withdrawal time, bowel preparation, submucosal injection, lesion location, and histopathology of the lesions.

To identify independent risk factors related to development of PPCS, multivariate analysis was performed after adjusting for age, hypertension, number of polypectomies, submucosal injection, and the size, location, shape, and histopathology of the lesions ([Table 4]). In this analysis, hypertension (OR = 3.023, 95 %CI 1.034 – 8.832), larger lesion size (OR = 2.855, 95 %CI 1.027 – 7.937), and non-polypoid configuration (OR = 3.332, 95 %CI 1.029 – 10.791) were found to be independent risk factors related to PPCS. 

Discussion

To our knowledge, this is the first study examining the clinical characteristics, clinical outcomes, and risk factors associated with PPCS. Few reports have examined this issue and the need for further data has been highlighted previously. Results from the current study showed that the rate of PPCS requiring hospitalization after colonoscopic polypectomy was 0.7/1000. Only cases of PPCS that required hospitalization were analyzed in the study. Therefore, patients with mild symptoms who may have responded to medical treatment at an outpatient clinic were excluded. This might explain why the rate of PPCS in this study was lower than that quoted in previous studies [12] [13] [14] [15] [16]. In clinical practice, significant cases with PPCS usually require hospitalization, and therefore knowledge about the outcomes and risk factors of hospitalized patients with PPCS is more important than those of all patients with PPCS. In one study, hospitalization was required in approximately 20 % of patients with PPCS, although an exact proportion of hospitalized patients was not known due to the small number of patients included (only two hospitalizations from a total of nine patients with PPCS) and the single-center design [12]. Earlier reports estimated the incidence of PPCS to be 0.5 % – 1.2 % of patients undergoing colonoscopic polypectomy [12] [13]. In two other series, 0.5 % of 4784 consecutive colonoscopic polypectomies developed PPCS [14], and 0.5 % of 1190 patients who underwent 1576 colonoscopic polypectomies developed PPCS [15]. In a more recent report, involving 1672 colonoscopic polypectomies, no cases of PPCS were identified [16]. It is important to take into consideration the definition of PPCS, study methodology, patient population, and endoscopist experience and specialty when evaluating the rate of PPCS between different studies. Although a valid definition of PPCS is one of the major problems in interpreting studies on this topic, the definition of PPCS was not clearly described in previous studies [12] [13] [14]. Developments in electrosurgical units and endoscopist experience and specialties may also be reflected in the lower rates of PPCS seen more recently.

Usually, PPCS is suspected in patients who develop the clinical features described above following colonoscopic polypectomy with electrocautery. In the literature, the majority of patients with PPCS complained of abdominal pain and tenderness in the region of the polypectomy site, and some patients presented with abdominal rigidity, fever, leukocytosis, and tachycardia [12] [13] [14] [15] [16]. In the current study, however, fever or leukocytosis was not always present in the patients with PPCS. Therefore, a combination of these symptoms in conjunction with a raised CRP, which showed 100 % sensitivity for the detection of PPCS, may be helpful for the diagnosis of PPCS. However, CRP alone is not a sufficient laboratory indicator of PPCS due to its non-specific nature. The patients with PPCS can be diagnosed with a combination of symptoms, signs, and laboratory findings that indicate peritonitis following a colonoscopic polypectomy.

In the current study, all patients with PPCS were treated medically without the need for surgical intervention, which was a consistent finding in a previous study by Waye et al. [12]. In terms of medical treatment, the median duration for therapeutic fasting, hospitalization, and antibiotic use were 3 days, 5.5 days, and 7 days, respectively. Furthermore, the rates of major complications and mortality were 2.9 % and 0 %, respectively. As the clinical course was excellent in most patients, patients whose symptoms do not respond or worsen despite medical management should be immediately re-evaluated for the possibility of perforation, which has symptoms and signs that closely resemble PPCS. 

There is scant information concerning risk factors for PPCS associated with colonoscopic polypectomy. On multivariate analysis of results from the current study, hypertension, large lesion size, and non-polypoid configuration were found to be independent risk factors related to PPCS. Christie et al. also described that two-thirds of 24 patients with PPCS had large sessile polyps [14]. PPCS is known to develop when electrical current applied during colonoscopic polypectomy extends past the mucosa into the muscularis propria and serosa, resulting in a transmural burn without perforation [11] [12] [13] [14] [15] [16]. Therefore, larger lesions and non-polypoid configuration are logical risk factors, as they usually require a large amount of thermal energy for a longer duration. However, the mechanism of hypertension to promote PPCS is unclear. Patients with hypertension are more likely to have endothelial dysfunction [22] and atherosclerosis [23] [24], which may be contributing factors. Theoretically, submucosal saline injection of large, non-polypoid lesions prior to colonoscopic polypectomy may reduce the risk of PPCS, the rationale being that submucosal saline injection may increase the thickness of the submucosal layer and consequently reduce the risk of PPCS. However, there are no studies supporting this assumption. Although submucosal saline injection did not demonstrate any protective effects for PPCS in the current study, results should be interpreted with caution because indications and the method of submucosal saline injection were not controlled in this retrospective study. Furthermore, the volume of injection solution used could be more relevant for the development of PPCS than the use or non-use of submucosal injection. However, data about the volume of injection solution were not collected in the study. Therefore, the protective role of the saline “cushion” for PPCS should be considered in future studies.

The current findings must be interpreted within the context of the strengths and weaknesses of the study. This study was the first large study evaluating the clinical outcomes and risk factors of PPCS. Only patients who were hospitalized for PPCS were included in order to avoid diagnostic uncertainty. There were also multiple possible confounders for potential risk factors for PPCS. Among the possible risk factors for PPCS, endoscopist experience and specialty were not evaluated in the current study due to general uniformity among the endoscopists. Retrospective design and missing data in some study variables were major limitations of the study, although important information was largely available, as only hospitalized patients were included and therefore the data were based on the university hospital records. Prospective data on PPCS associated with colonoscopic polypectomy in both inpatient and outpatient settings might provide the exact status of all PPCS, but there has been a lack of such data and such studies would require a huge number of patients. Retrospective data on PPCS including both inpatient and outpatient settings may also raise the issue of diagnostic uncertainty for the outpatients with PPCS.

In conclusion, the rate of PPCS that required hospitalization after colonoscopic polypectomy was 0.7/1000, and the rates of major complications and mortality were only 2.9 % and 0 %, respectively. Hypertension, large lesion size, and non-polypoid configuration of the lesions were independently associated with PPCS. Therefore, patients with PPCS may be reassured of an excellent prognosis, while endoscopists need to be especially careful when performing colonoscopic polypectomies in patients with hypertension or large and non-polypoid lesions.

Competing interests: None.

Acknowledgment

Produced on behalf of the Korean Association for the Study of Intestinal Disease (KASID).

• References

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Corresponding author

• References

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• 2 Parra-Blanco A, Kaminaga N, Kojima T et al. Colonoscopic polypectomy with cutting current: is it safe?. Gastrointest Endosc 2000; 51: 676-681
  CrossrefPubMedSearch in Google Scholar
• 3 Gibbs DH, Opelka FG, Beck DE et al. Postpolypectomy colonic hemorrhage. Dis Colon Rectum 1996; 39: 806-810
  CrossrefPubMedSearch in Google Scholar
• 4 Rosen L, Bub DS, Reed 3rd JF et al. Hemorrhage following colonoscopic polypectomy. Dis Colon Rectum 1993; 36: 1126-1131
  CrossrefPubMedSearch in Google Scholar
• 5 Nivatvongs S. Complications in colonoscopic polypectomy. An experience with 1,555 polypectomies. Dis Colon Rectum 1986; 29: 825-830
  CrossrefPubMedSearch in Google Scholar
• 6 Webb WA, McDaniel L, Jones L. Experience with 1000 colonoscopic polypectomies. Ann Surg 1985; 201: 626-632
  CrossrefPubMedSearch in Google Scholar
• 7 Heldwein W, Dollhopf M, Rösch T et al. The Munich Polypectomy Study (MUPS): prospective analysis of complications and risk factors in 4000 colonic snare polypectomy. Endoscopy 2005; 37: 1116-1122
  Thieme ConnectPubMedSearch in Google Scholar
• 8 Arora G, Mannalithara A, Singh G et al. Risk of perforation from a colonoscopy in adults: a large population-based study. Gastrointest Endosc 2009; 69: 654-664
  CrossrefPubMedSearch in Google Scholar
• 9 Watabe H, Yamaji Y, Okamoto M et al. Risk assessment for delayed hemorrhagic complications of colonic polypectomy: polyp-related factors and patient-related factors. Gastrointest Endosc 2006; 64: 73-78
  CrossrefPubMedSearch in Google Scholar
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  CrossrefPubMedSearch in Google Scholar
• 15 Nivatvongs S. Complications in colonoscopic polypectomy: lessons to learn from an experience with 1576 polyps. Am Surg 1988; 54: 61-63
  PubMedSearch in Google Scholar
• 16 Nelson DB, McQuaid KR, Bond JH et al. Procedural success and complications of large-scale screening colonoscopy. Gastrointest Endosc 2002; 55: 307-314
  CrossrefPubMedSearch in Google Scholar
• 17 The Paris endoscopic classification of superficial neoplastic lesions: esophagus, stomach, and colon: November 30 to December 1, 2002. Gastrointest Endosc 2003; 58: 3-43
  CrossrefPubMedSearch in Google Scholar
• 18 Schlemper RJ, Hirata I, Dixon MF. The macroscopic classification of early neoplasia of the digestive tract. Endoscopy 2002; 34: 163-168
  Thieme ConnectPubMedSearch in Google Scholar
• 19 Hamilton SR, Aaltonen LA eds. World Health Organization classification of tumours: pathology and genetics of tumors of the digestive system. 1st. edn. Lyon: IARC Press; 2000: 103-143
  Search in Google Scholar
• 20 Kurome M, Kato J, Nawa T et al. Risk factors for high-grade dysplasia or carcinoma in colorectal adenoma cases treated with endoscopic polypectomy. Eur J Gastroenterol Hepatol 2008; 20: 111-117
  CrossrefPubMedSearch in Google Scholar
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  CrossrefPubMedSearch in Google Scholar
• 22 Egashira K, Inou T, Hirooka Y et al. Imparied coronary blood flow response to acetylcholine in patients with coronary risk factors and proximal atherosclerotic lesions. J Clin Invest 1993; 91: 29-37
  CrossrefPubMedSearch in Google Scholar
• 23 Ross R. The pathogenesis of atherosclerosis – an update. N Engl J Med 1986; 314: 488-500
  CrossrefPubMedSearch in Google Scholar
• 24 MacMahon S, Peto R, Cutler J et al. Blood pressure, stroke, and coronary heart disease. Part 1, Prolonged differences in blood pressure: prospective observational studies corrected for the regression dilution bias. Lancet 1990; 335: 765-774
  CrossrefPubMedSearch in Google Scholar