1. Optimal Bowel Preparations for Colonoscopy
F1 박선진 / Prof. 이창균

2. 대장암 사망률 53% 감소 Zauber AG, et al. NEJM 2012; 366; 687-696
내시경적 용종 절제술은 선종의 암화 과정을 blcok하여 대장직장암으로의 진행을 막을 수 있다.
2012년 NEJM에 보고된 연구에서 선종이 제거된 2천명이상의 환자를 20년 이상 f/u 하였을 때 53% 감소하는 것으로 보고하였습니다.
Zauber AG, et al. NEJM 2012; 366;
대장암 사망률 53% 감소

3. 대장정결 목표 Polyp (>5mm) detection
If not, additional bowel cleansing or reschedule with more preparation, <1yr
Johnson DA, et al. GIE 2014
Johnson DA, et al. GIE 2014

4. Agenda Effect of quality of preparation Bowel preparation agents
Preparation instructions
Dietary modification

5. Effect of quality of preparation

6. Effect of quality of preparation
Adequate preparation
Inadequate preparation
Diagnostic accuracy
Therapeutic safety
Missing neoplasm
Repeat examination (increase cost)
Rex DK et al. Gastrointest Endosc 2006
Chokshi RV et al. Gastrointest Endosc 2012
Wexner SD et al. Gastrointest Endosc 2006

7. Inadequate bowel prep
부적절한 장정결의 예를 보시겠습니다. 대량의 변을 suction하고 자세변동을 통해 LST를 발견할 수 있었습니다.

8. Inadequate bowel prep Inadequate prep 76.9% Adequate prep
Bowel preparation is inadequate for almost a quarter of patients undergoing colonoscopy. (23.1%, 21,503/93,004 cases)
Harewood et al. Gastrointest Endosc 2003;58:76-79.
Bowles et al. Gut 2004;53:

9. Effects of bowel prep on colonoscopy
3년 이내 다시 시행했을 때
Lebwohl B, et al. Gastrointest Endosc 2011; 73:

10. Effects of bowel prep on colonoscopy outcome measures
European prospective multicenter study (n = 5832)
Outcome
Low-quality prep
High-quality prep
P value
Compeletion (%)
71.7
90.4
<0.001
Mean time to cecum (min)
16.1
11.9
Mean withdrawal time (min)
11.3
9.8
Polyps of any size (%)
23.9
29.4
.007
Polyps > 10 mm detected (%)
4.3
6.4
.016
유럽다기관 연구
Froehlich et al. Gastrointest Endosc 2005;61:

11. Effects of bowel prep on colonoscopy
At screening, ≥1 adenoma -> 3mo
Missing 19.9% polyps & 17.8% adenomas
Pts with missed lesion
(OR)
Polyp
Adenoma
Advanced adenoma
Aronchick scale
Excellent 1
Good
1.44
1.45
2.00
Fair
1.32
1.27
2.12
Poor/Inadequate
3.21
3.04
5.28
Hong SN, et al. Clin Endosc 2012
Hong SN, et al. Clin Endosc 2012

12. 65 female, Constipation, Repeat colonoscopy after inadequate prep
LST-NG Submucosal invasive cancer

13. Bowel preparation agent

14. Ideal bowel preparation
Empty colon without mucosal histologic alternation
Safety, Efficacy, Tolerability & Cost

15. 대장정결제의 종류 Isosmotic Full Volume Preps Isosmotic Low Volume Preps
PEG-ELS
PEG-sulfate free
Isosmotic Low Volume Preps
PEG and bisacodyl
PEG and ascorbic acid
Hyper-Osmotic Low Volume Preps
Sodium Picosulfate and Mg citrate
Oral sodium sulfate
NaP tablets
Mg Citrate and bisacodyl
Isosmotic Full Volume Preps
•Colyte (PEG-ELS)
•GoLYTELY (PEG-ELS)
•NuLYTELY (PEG-sulfate free)
•TriLyte (PEG-sulfate free)
Isosmotic Low Volume Preps
•HalfLytely (Braintree Labs; PEG and bisacodyl)
•MoviPrep (Salix Pharm; PEG and ascorbic acid)
Hyper Osmotic Preps
•OsmoPrep (Salix; NaP tablets)
•LoSo Prep (Bracco; Mg Citrate + bisacodyl)
•Suprep (Braintree Labs; Na Sulfate)
•Prepopik (Ferring; Sodium Picosulfate + Mg oxide + citric acid)

16. The Great Beginning of Modern bowel preparation with the advent of PEG solution
Davis GR et al. Gastro 1980;78:

17. High volume PEG 작용기전 장점 단점
PEG(non-absorbable) & Electrolyte(isosmotic)
->수분과 전해질 이동을 최소화 장점
안전, 정결효과 우수, 대장 점막의 조직학적 변화 없음 단점
4L 복용, 불쾌한 맛, 짠맛, 구토, 복통
-> 5-15% 환자 복용 중단

18. Low-volume PEG
2L PEG-ELS with ascorbate

19. Low-volume PEG with Asc Full volume vs. Low volume
2L PEG + Asc (n=202) vs. 4L PEG (n=198), RCT in Europe
Satisfactory colon cleansing
Same
94.1% vs. 90.9%
P=ns
Compliance
Better
80% vs. 70%
P=.025
Willingness to repeat
87% vs. 51%
P<.001
Reduction in side effect
80.2% vs. 89.9%
P=.011
Ponchon T et al. Dig Liver Dis 2013;45:820-6.

20. Na Picosulfate + Mg citrate
84.4%
72.7%
Higher quality of BP with PEG + Asc
In overall colon
In ascending colon and cecum
Worthington J et al, Curr Med Res Opin. 2008;24:

21. Na Picosulfate + Mg citrate safety
2L PEG + Ascorbic acid
Na Picosulfate + Mg citrate
100g of PEG
Balanced electrolyte solution
Additional cathartic effect by ascorbic acid
Picosulfate
Stimulant, Peristalsis
Risk of hypovolemia, hyponatremia
Cautions in diuretics, CHF, Cirrhosis, CKD
Additional cathartic effect by Mg citrate
Relatively contraindication in patients with CKD
ASGE 가이드라인에서는 노인이나 신장질환이나 전해질 이상 유발 가능한 약제 복용 환자에서는 Na picosulfate Mg citrate 복합제제 복용하지 말것을 권고하고 있다.
Connor A et al, Gut 2012;61:

22. Na Picosulfate + Mg citrate safety
6. We recommend that sodium phosphate and magnesium citrate preparations not be used in the elderly or patients with renal disease or taking medications that alter renal blood flow or electrolyte excretion.
ASGE 2014

23. Osmotic laxative -Oral sodium sulfate
Multicenter, randomized study
Efficacy - OSS> PEG 4L
No deference of GI side effects & adverse effect
Osmotic laxative –탈수, 전해질 변화
-> CKD, diuretics 복용시 금기
PEG 4L 솔루션보다 우수하다는 보고도 있으나 삼투성 하제라서 탈수, 전해질 변화 가 있을 수 있어신장기능 이상이나 diuretics 복용시 금기입니다.
Rex DK, et al. GIE 2010

24. Preparation instructions

25. Split vs. Same day: Prep Quality 4L PEG-ELS
Kilgore TW et al. Gastrointest Endosc. 2011;73:
Enestvedt BK et a. Clin Gastroenterol Hepatol 2012;10:

26. Split vs. Non-split in different colon segments
Frequency of excellent/good bowel cleansing in different
colon segments according to the split-dosage versus non-split-dosage
intake schedule. P for all comparisons.
Volume 81, No. 4 : 2015 GASTROINTESTINAL ENDOSCOPY 781
Marmo R et al. Gastrointest Endosc 2015;81:
Marmo R et al. Gastrointest Endosc 2010;72:313-20

27. Split Dose Adequate preparation(Meta-analyses, 29)
Split- dose 85%> same-day 63%
ADR on multicenter study
Split-dose (OR 1.26, )
Bucci C, et al. GIE 2014
Jover R, et al. GIE 2013
Bucci C, et al. GIE 2014
Jover R, et al. GIE 2013

28. 4L PEG Split-Dosing: A meta-analysis
Split-dose PEG is superior to full-dose PEG with respect to…
Satisfactory colon cleansing
YES
OR 3.70; 95% CI,
OR 3.46; 95% CI,
Compliance ?
OR 0.53; 95% CI,
OR 1.41; 95% CI,
Willingness to repeat
OR 1.76; 95% CI,
OR 0.79; 95% CI
Reduction in side effect
Same
OR 0.55; 95% CI,
Kilgore TW et al. Gastrointest Endosc. 2011;73:
Enestvedt BK et a. Clin Gastroenterol Hepatol 2012;10:

29. The Golden Time: 2nd Dose
Colonoscopy should be performed within 8 hours of the last dosing.
마지막 복용이후 8시간 이전에 검사를 시행한 그룹에서 장정결도가 더 좋았다.
Marmo R et al. Gastrointest Endosc 2010;72:313-20

30. The Golden Time: 2nd Dose
The second dose of split preparation ideally should begin 4-6 hours before the time of colonoscopy with completion of the last dose at least 2 hours before the procedure time.
The delay between the last dose of bowel preparation and colonoscopy should be minimized and no longer than 4 hours.
ASGE 2014
USMSTF 2014
ESGE guideline 2013
ESGE 2013

31. “Prep-to-Colon” interval
For every additional hour, chance of good/excellent prep drops 10%.
A 3-5 hour interval appears ideal with split dosing.
Seo EH, Kim TO, et al. Gastrointest Endosc 2012;75:583-90
Eun CS, Han DS, et al. Dig Dis Sci 2011;56:
Vs. 5-7 hr, P = .004
Vs. >7 hr, P < .001

32. Morning only prep for PM colono 2L PEG with Asc
Non-inferiority
Non-inferiority
No Difference
Matro R et al. Am J Gastroenterol 2010;105:

33. Morning only prep for PM colono 2L PEG with Asc
Matro R et al. Am J Gastroenterol 2010;105:

34. Summary: Putting Patients First!
Timing is Everything
Split-dosing is clearly superior
Same-day prep is OK for afternoon CFS
Do the procedure 3-5 hours after the last ingestion
Volume is the matter
Low volume preps: similar efficacy, safety, & better tolerability than 4L PEG
2L PEG with Asc is superior to SPMC with regard to efficacy and safety
What is an ideal bowel prep?
Efficacy, Safety, and Tolerability
When compliance is an issue?

35. Efficacy, Safety, and Tolerability
Ideal Bowel Prep:
Efficacy, Safety, and Tolerability
Efficacy:
4L-PEG, 2L-PEGA, 2L-PEGB, SPMC, NaP
Safety:
4L-PEG,
2L-PEGA
Tolerability:
2L-PEGA,
2L-PEGB,
SPMC, NaP
궁극적으로 재검사의 의향을 높이는 것이 surveillance exam에 매우 중요하다
PEGA: PEG+ascorbic acid
PEGB: PEG+bisacodyl
SPMC: Na picosulfate+Mg citrate

40. Predictive or influencing factor
Predictor OR
95% CI
Procedure time
1.15
(1.05, 1.25)
Preparation instructions not followed
2.68
(1.52, 4.75)
History of cirrhosis
3.71
(1.17, 11.75)
Inpatient status
3.13
(1.15, 8.50)
Constipation
2.81
(1.10,7.20)
TCA
2.99
(1.10, 8.15)
History of polyps
0.55
(0.31, 0.98)
Male gender
1.54
(1.03, 2.30)
History of stroke or dementia
2.23
(1.00, 4.97)
Ness RM, et al. Am J Gastroenterol 2001

41. Predictive or influencing factor
Ronald v, world j gastroenterol

42. Predictive or influencing factor

43. 환자교육 대장정결 향상을 위해 장정결 방법에 관한 교육
Rosenfeld G. et al, 2010
Rosenfeld G. et al, Can J Gastroenterol. 2010

44. Prep Advice is critical for compliance
Patient handouts/instruction booklets2
Ensure adequate font, use passive voice, simple language, logical order, intuitive headings, repetition, concrete examples (eg: of “clear liquids”), FAQs
Patient centered/validated
Spiegel BM. Am J Gastroenterol 2011;106:
Liu X et al. Gut 2014;63:125-30

45. Dietary modification

46. Dietary modifications
Less strict dietary restriction improves patient tolerance for preparation.
ASGE recommends a low-residue diet be used for bowel preparation
ESGE recommends a low-fiber diet on the day preceding colonoscopy
식이에 있어서 미국과 유럽이 다르다. 유럽에서는 저섬유식을 검사 전날만 시행하도록 권고하고 있다.
최근에는 엄격한 식이 제한이 순응도를 떨어뜨릴 수 있다는 의견이 있어.

47. Clear liquid diet vs Regular diet
PEG 4L preparation
Multicenter, randomized, investigator-blind
CLD(n=405)
RD(n=396)
P value
Bowel cleansing
Adequate(exellent & good)
338 (83.5)
330 (83.3)
0.963
Excellent
128 (31.6)
94 (23.7)
0.013
Good
220 (51.9)
236 (59.6)
0.027
Fair
45 (11.1)
51 (12.9)
0.441
Poor
22 (5.4)
15 (3.8)
0.268
Good comliance (PEG≥3L)
364 (89.9)
379 (95.7)
0.001
Jung Ys, et al. Gut Liver
Jung Ys, et al. Gut Liver

48. Dietary modifications
Adquate bowel prep
저섬유식 81.4 % vs 맑은 유동식 52 % (P<0.001)

49. Dietary modifications

51. Clear/semiclear
Brown liquid/ solid

52. Conclusion To improve bowel preparation for colonoscopy
환자상태, 순응도, 부작용을 고려한 안전한 대장 정결제의 선택
적절한 복용법
환자교육
식이에 있어서 미국과 유럽이 다르다. 유럽에서는 저섬유식을 검사 전날만 시행하도록 권고하고 있다.
최근에는 엄격한 식이 제한이 순응도를 떨어뜨릴 수 있다는 의견이 있어.