Research article Open Access
Complications of ERCP among Patients Aged Less Than 40 Years: A Retrospective Study from a Tertiary Center
Leila Alizadeh and AH Mohammad Alizadeh*
Shahid Beheshti University of Medical Sciences, Taleghani Hospital, Parvaneh Ave, Tabnak Str, Evin, Tehran, Iran
*Corresponding author: Mohammad Alizadeh AH, Shahid Beheshti University of Medical Sciences, Taleghani Hospital, Parvaneh Ave, Tabnak Str, Evin, Tehran, Iran-19857,Tel:0098-21-22432521;Fax: 0098-21-22432517; E-mail: @
Received: July 7, 2016; Accepted: August 28, 2016; Published: September 13, 2016
Citation: Alizadeh L, Mohammad Alizadeh AH (2016) Complications of ERCP among Patients Aged Less Than 40 Years: A Retrospective Study from a Tertiary Center. Gastroenterol Pancreatol Liver Disord 3(5): DOI: http://dx.doi.org/10.15226/2374-815X/2/4/00168
Abstract
Background: Pancreatitis is considered the most common complication of ERCP especially among the younger age group. The risk factors for post-ERCP pancreatitis (PEP) are still debated. This study aimed to assess complications following ERCP technique in patients under 40 years and investigate whether young age is a risk factor of PEP.

Materials and Methods: Records of all the patients <40 years old undergone ERCP from Jan 1997until Jan 2016 in Taleghani hospital were included in this retrospective study. A questionnaire including demographic characteristics of patients including age, sex, smoking, alcohol consumption, and opium addiction was completed for each patient. Clinical characteristics comprised of PEP history, pancreatitis history, sphincter of oddi dysfunction (SOD), Primary sclerosing cholangitis(PSC), ERCP associated factors including ERCP type (therapeutic or diagnostic), sphincrotomy, pancreatic duct (PD) interance, PD injection, PD stenting, TTS, needle knife during ERCP and death as an outcome were also recorded. Studies laboratory tests included CRP (negative or positive), Amylase, Bilirubin Total, WBC, Triglyceride, ESR, ALT, and AST. Descriptive statistics and Chi-square test were used for data analysis.

Results: A total of 424 participants were recruited in this study. Mean age of participants was 31.5 ± 6.5 years old. 56% (223) of participants were female. Sixty four (15%) of recruited ERCPs developed PEP. History of pancreatitis, diagnostic and therapeutic ERCP, and needle knife intervention during ERCP were associated with PEP with significant difference (P-values: 0.001, 0.02, 0.03, and 0.04, respectively). Amylase level also estimated to be a significant risk factor of PEP (P-value: <0.001).

Conclusion: Current study along with previous studies estimated high incidence of PEP among patients<40 years. In this age group, history of pancreatitis, diagnostic and therapeutic ERCP, and needle knife intervention during ERCP and higher level of amylase were significant predicting risk factors of PEP and should be considered during selecting patients for ERCP to avoid complications. Keywords: ERCP; Pancreatitis; Post ERCP pancreatitis
Introduction
Endoscopic retrograde cholangiopancreatography (ERCP) is a well-known and widely used technique for treating biliary obstruction. It is reported to have high diagnostic and therapeutic value for biliary stones in older age group. Complications following ERCP seem to be high in elderly because of co-morbidities. Factors such as type of sedation, the severity of illness or underlying malignancies are showed to be involved in complications of ERCP [1]. 5-10% of patients undergoing ERCP develop complications [1, 2]. ERCP has a complication rate ranging between 4% and 16% such as post-ERCP pancreatitis, hemorrhage, cholangitis and perforation. Perforation rate is also reported as 0.08% to 1% and mortality rate ups to 1.5% of ERCPs [3].

Pancreatitis is considered the most common complication of ERCP with reported incidence of 4-8% in most prospective studies and it ups to 40% in high-risk patients [1, 2, 4-6]. More prevalence of pancreatitis is reported in younger age group but the other complications are reported more in elderly [1]. Prevention strategies targeting risk factors could be important to reduce the rate of post-ERCP pancreatitis (PEP) [4]. PEP may be an avoidable complication. Although pancreatitis of severe grade is reported in 0.1%-0.5% of ERCP patients, but a serious clinical course may be lethal [5]. Thus, identifying risk factors of PEP and then patient risk stratification could be considered as a prevention strategy for PEP [5]. However, the risk factors for PEP are still debated and this warrants conducting further studies to investigate risk factors of PEP [4]. Agarwal et al in a retrospective study of 221 ERCPs in children< 18 years old reported incidence of ERCP related adverse events as 4.7% and concluded that ERCP could be used safely in the treatment of pancreatic disorders in children [7]. Alizade et al also indicated diagnostic ERCP as a safe and well tolerated procedure in older than young patients. High risk predictors of PEP include patient's age, previous history of post-ERCP pancreatitis, and technical factors (number of minor papilla sphincterotomy and operator experience) [1]. Ding et al in a systematic review of risk factors of PEP did not report age as a risk factor. They indicated that female gender, previous pancreatitis, previous PEP, Sphincter of Oddi dysfunction (SOD), Intraductal papillary mucinous neoplasm (IPMN), difficult cannulation, for endoscopic sphincterotomy (EST), precut sphincterotomy and main pancreatic duct injection are risk factors for PEP [4]. Yun et al also did not report older age as a risk factor of ERCP and they concluded that ERCP can be performed safely and successfully in patients aged 90 years and older without any significant increase in complications [8]. Hernandez et al in a study in the national Cuban institute reported peridiverticular location of the papilla and the SOD as the patient related risk factors of PEP without mentioning age as a risk factor for developing PEP [9].

Other studies have indicated the fallowing risk factors for developing PEP: young women with abdominal pain, normal liver tests, and unremarkable imaging. Procedure-related factors include traumatic and persistent cannulation attempts, multiple injections of the pancreatic duct, pancreatic sphincterotomy, and, possibly, use of precut sphincterotomy [10].

Nakai et al has reported guide wire insertion into the PD and a small CBD as risk factors for PEP in biliary therapeutic ERCP with the use of wire-guided cannulation (WGC) [11].

In conclusion, the risk factors for post-ERCP pancreatitis (PEP) are still debated and there is need to perform further studies to identify PEP risk factors. This study aimed to assess complications following ERCP technique in patients under 40 years and investigate whether young age is a risk factor of PEP. The current study findings would help clinicians to stratify their patients according to the risks of PEP and consider preventive strategies for PEP as a common complication of ERCP.
Materials and Methods
This study was a cross-sectional study conducted at Taleghani Hospital affiliated with Shaiid Beheshti University of Medical Sciences. Records of all the patients <40 years old undergone ERCP from Jan 1997 until Jan 2016 in Taleghani hospital were included in this retrospective study. The first ERCP of the patients was recorded in the study. Consent forms were obtained from all study participants. The study was approved in Shaeed Beheshti University of Medical Sciences.

Patients who refused to participate in the study, and patients with incomplete records were excluded from the study. All the patients <40 years old undergone ERCP were included in the study consecutively except those with exclusion criteria.

A questionnaire including demographic characteristics of patients including age, sex, smoking, alcohol consumption, and opium addiction was completed for each patient. Clinical characteristics comprised of PEP history, pancreatitis history, sphincter of oddie dysfunction (SOD), PSC, ERCP associated factors including ERCP type (therapeutic or diagnostic), sphincrotomy, pancreatic duct (PD) interance, PD injection, PD stenting, TTS, needle knife during ERCP and death as a outcome were also recorded for each participant. Laboratory tests included CRP (negative or positive), Amylase, Bilirubin Total, WBC, Triglyceride, ESR, ALT, and AST were recorded. Amylase:3 times higher than upper limit of normal range that was considered as 100 International unit/liter , Bilirubin Total> 2, WBC > 10000, Triglyceride > 150, AST and ALT > 40 were considered as abnormal finding for further analysis. Data were analyzed using SPSS version 16. Descriptive statistics and Chisquare test were used for data analysis. P-value≥0.05was defined as significant statistical association.
Results
A total of 424 participants were recruited in this study. Mean age of participants was 31.5 ± 6.5 years old. 56% (223) of participants were female. Fifteen percent (64) of recruited ERCPs developed PEP. Current smoking was much more prevalent among those without PEP with no significant statistical difference (Table 1). Alcohol consumption and opium addiction were more likely to be reported by patients without PEP but the observed association was not significant (Table 1). No significant association was observed between the groups with and without PEP in terms of CBD dilation, SOD, Diverticulum, PD stenting, PD interance, PD injection, and PSC. Twoand 62 participants undergone diagnostic and therapeutic ERCP, respectively developed PEP with significant statistical difference (P-value <0.05, Table 1).

Pancreatitis history was more common among patients with PEP with significant statistical association (P-value: 0.001, Table 1) however, PEP history was not found to be a risk factor for current PEP (p-value>0.05, Table 1.). Among ERCP associated interventions, needle knife was observed to be higher in the group of patients with PEP (P-value <0.05, Table 1) but as mentioned earlier in the results, other interventions such as PD injection, PD stenting, PD interance were less common in the group with PEP.

PEP was more frequent in participants with abnormal Amylase with significant association (P-value < 0.001, Table 2). There was no significant difference between the participants with PEP and no PEP in terms of following lab findings: CRP, ESR, Bilirubin total, WBC, Triglyceride, liver function tests (AST and ALT) (Table 2). Abnormal LFT in combination with pancreatitis history was observed in 8 PEP cases and the association was not significant (Table 2). Death occurred in one patient who had not PEP
Discussion
In current study, 64 (15%) of participantsundergone ERCP developed PEP with more than half female predominance. Associated risk factors for developing ERCP complications included history of pancreatitis, diagnostic and therapeutic ERCP, and needle knife intervention during ERCP. Among laboratory findings amylase level estimated to be a significant risk factor of PEP.

Christensen et al in a study of 1177 ERCPs has estimated rate of PEP to be 3.8% which seems to be lower than current study [12]. The reported incidence of pancreatitis following ERCP is 4-8% up to 40% in high risk patients [1, 2, 4-6]. It is also indicated that younger age group has more prevalence of pancreatitis which is consistent with higher prevalence of PEP among participants less than 40 yearsin this study [1, 12].
Table 1: Demographic and clinical characteristics of study participants.

Variable

 

PEP (n=64)

No PEP (n=360)

P-value

Sex

 

 

 

0.92

 

Male

30 (14)*

171 (85)

 

 

Female

34 (15)

189 (84)

 

Current Smoking

 

 

 

0.54

 

yes

7 (18)

31 (81)

 

 

no

57 (14)

329 (85)

 

Alcohol Consumption

 

 

 

0.53

 

yes

1 (10)

9 (90)

 

 

no

63 (15)

351 (84)

 

Opium Addiction

 

 

 

0.51

 

yes

0

4

 

 

no

64 (15)

356 (64)

 

SOD

 

 

 

0.22

 

yes

3 (27)

8 (72)

 

 

no

61 (14)

352 (85)

 

CBD dilation

 

 

 

0.86

 

yes

30 (14)

173 (85)

 

 

no

34 (15)

187 (84)

 

PEP History

 

 

 

0.27

 

yes

1

1

 

 

no

63 (14)

359 (85)

 

Pancreatitis History

 

 

 

*0.001

 

yes

14 (31)

30 (68)

 

 

no

50 (13)

330 (86)

 

Therapeutic ERCP

 

 

 

*0.03

 

yes

62 (16)

317 (83)

 

 

no

2 (4)

43 (95)

 

Diagnostic ERCP

 

 

 

*0.02

 

yes

2 (4)

41 (95)

 

 

no

62 (16)

319 (83)

 

Sphincrotomy during ERCP

 

 

 

0.71

 

yes

55 (15)

303 (84)

 

 

no

9 (13)

57 (86)

 

Diverticulum

 

 

 

0.50

 

Positive

4 (16)

20 (83)

 

 

Negative

60 (15)

340 (85)

 

Needleknife

 

 

 

*0.04

 

yes

4 (40)

6 (60)

 

 

no

60 (14)

354 (85)

 

PDinterance

 

 

 

0.20

 

yes

5 (25)

15 (75)

 

 

no

59 (14)

344 (85)

 

PD injection

 

 

 

0.33

 

yes

3 (25)

9 (75)

 

 

no

61 (14)

351 (85)

 

TTS

 

 

 

0.13

 

positive

6 (26)

17 (73)

 

 

negative

58 (14)

343 (85)

 

CBD Stone

 

 

 

0.96

 

yes

24 (15)

136 (85)

 

 

no

40 (15)

224 (84)

 

PD Stenting

 

 

 

0.10

 

yes

4 (30)

9 (69)

 

 

no

60 (14)

351 (85)

 

PSC

 

 

 

0.33

 

yes

9 (19)

37 (80)

 

 

no

55 (14)

323 (85)

 

Death

 

 

 

-

 

yes

0

1

 

 

no

64 (15)

359 (84)

 

*Data are presented as number (percent)
ERCP: Endoscopic retrograde cholangiopancreatography, PEP: Post ERCP Pancreatitis, SOD: Sphincter of Oddie dysfunction, PD: Pancreatic duct, TTS: [Balloon] Through The Scope, CBD: Common bile duct, PSC: Primary Sclerosing Collangitis.
Participants with history of pancreatitis were more likely to become complicated after ERCP in present study. Cotton et al in a multivariate-analysis of 11497 ERCPs showed that patients with history of acute or chronic pancreatitis develop fewer complications [13]; however, in another study conducted by Vandervoort et al on 1223 ERCPs, an identified history of recurrent pancreatitis was reported as one of the predicting risk factors of ERCP [14]. Although there is controversy about increasing risk of PEP by history of pancreatitis; present results were along with the studies which have reported history of pancreatitis as a risk factor of PEP [14]. Therapeutic or diagnostic ERCP is reported to be also associated with complications of this procedure. Cotton et al has showed higher incidence of complications in therapeutic ERCPs [13]. This study also showed increased rate of PEP in both diagnostic and therapeutic ERCPs, however, it should be noted that sample size in those who developed PEP with diagnostic ERCP was low and it could be source of bias in observed association.

Although previous studies have mentioned higher incidence of PEP in patients with SOD, previous PEP, multiple cannulations, stent placement, sphincrotomy, and PD injection but current study didn't confirm such association that may be due to low sample size [4, 12-14]. Moreover, patients with PEP were more likely to have normal LFT which is consistent with results of previous reports [10].

Cross sectional and retrospective design which confines generis ability of the findings and low sample size are considered limitations of this study, therefore conducting prospective studies with larger sample sizes is recommended for future investigations.

In conclusion, current study along with previous studies estimated high incidence of PEP among patients <40 years. In this age group, history of pancreatitis, diagnostic and therapeutic ERCP, and needle knife intervention during ERCP and higher level of amylase were significant predicting risk factors of PEP and should be considered during selecting patients for ERCP to avoid complications.
Table 2: Laboratory findings of study participants

Laboratory

 

PEP (n=64)

No PEP (n=360)

P-value

CRP

 

 

 

0.47

 

positive

14 (12)*

94 (87)

 

 

negative

50 (15)

266 (84)

 

Amylase(IU/liter)

 

 

 

*0.0001

 

3times higher than upper limit of normal range (0-100)

47 (66)

24 (33)

 

 

3 times lower than upper limit of normal range (0-100)

17 (4)

336 (95)

 

Bilirubin Total(mg/dl)

 

 

 

0.38

 

> 2

36 (13)

223 (86)

 

 

< 2

28 (16)

137 (83)

 

WBC count

 

 

 

0.12

 

> 10000

16 (20)

61 (79)

 

 

<10000

48 (13)

299 (86)

 

Triglyceride(mg/dl)

 

 

 

0.83

 

> 150

22 (15)

119 (84)

 

 

<150

42 (14)

241 (85)

 

ESR (According to age)(mm/hr)

 

 

 

0.08

 

abnormal

6 (8)

65 (91)

 

 

normal

58 (16)

295 (83)

 

AST (IU/liter)

 

 

 

 

 

> 40

40 (14)

239 (85)

 

 

<40

24 (66)

12 (33)

 

ALT(IU/liter)

 

 

 

0.19

 

> 40

44 (13)

275 (86)

 

 

<40

20 (19)

85 (80)

 

Abnormal LFT/ Pancreatitis History

 

 

 

0.12

 

yes

8 (24)

25 (75)

 

 

no

56 (14)

335 (85)

 

*Data are presented as number (percent) IU: International Unit, CRP: C Reactive Protein, WBC: White Blood Cell, ESR: Erythrocyte Sedimentation Rate AST: Aspartate Amino Transferase, ALT: Alanin Amino Transferase, LFT: Liver Function Test.
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