Professor Changlin Zhao: Why is a colonoscopy preferred for fine screening for coloral cancer? How can I improve the detection rate and early diagnosis accuracy of colorectal tumors on colonoscopy?

Author:Zhao Changlin

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Expert profile

Professor Zhao Changlin

• National Grade III Professor Ph.
  D.
  in Oncology

• Chief Physician of Xinhua Hospital Affiliated to Dalian University

• Head of Dalian Colon and Rectal Cancer Diagnosis and Treatment Base
  

• Vice President of Dalian Community Health Service Research Association
  

• Chairman of Dalian Community Cancer Prevention and Control Committee
  

• Standing Committee Member of Liaoning Provincial Gastric Cancer Professional Committee of China Anti-Cancer Association
  

• Standing Committee Member of Liaoning Base of Abdominal Oncology Committee of Chinese Medical Education Association
  

• Member of the Editorial Board of the 3rd Editorial Board of Chinese General Surgery Literature (Electronic Edition).
  
  

• The 2nd Editorial Board of the Chinese Electronic Journal of Coloral Diseases invited review expert

introduction

In recent years, the literature on colorectal cancer screening published at home and abroad and colorectal cancer diagnosis and treatment guidelines, colorectal cancer screening guidelines (hereinafter referred to as "guidelines"), etc.
, for the general risk population colorectal cancer screening is almost inclined to the initial screening and fine screening of layered screening, that is, through relatively easy to achieve, and simple, economical and effective colorological cancer primary screening method (quantitative FIT, etc.
), in the general risk population early detection of coloral cancer high-risk population, or suspected colorectal cancer population after the fine screening
。 This stratified screening strategy can significantly reduce the screening population, reduce the number of non-essential colonoscopy, improve the efficiency of colorectal cancer screening, further improve the detection rate and diagnostic accuracy of early colorectal cancer and precancerous lesions, effectively control false negatives, avoid missed diagnosis, and can save medical resources and screening costs, which is more cost-effective and in line with China's national conditions
.
So, what are the current methods used for coloral cancer screening? From the perspective of accuracy, efficacy and safety, how to choose the fine screening method?

Evaluation of fine screening methods in coloral cancer screening

In recent years, the refined screening methods used for colorectal cancer screening include colonoscopy, sigmoidoscopy, CT colonography (CTC), multi-target fecal DNA (mt-sDNA), and colon capsule endoscopy (CCE
).

Figure 1 Colorectal cancer screening: how to choose the fine screening method?

At present, the domestic and foreign guidelines recommend the same screening method for coloral cancer screening, but there is a consensus on the priority recommendation of colonoscopy: colonoscopy is the gold standard for colorectal cancer screening (strong recommendation, GRADE evidence rating: high, grade I recommended).

There are objections to the selection and recommendation levels of sigmoidoscopy, CTC, mt-sDNA, and CCE
.
Guidelines are constantly updated for results for sigmoidoscopy (weak recommendation, GRADE evidence rating: medium); CTC (weak recommendation, GRADE evidence rating: low, grade III recommended); mt-sDNA can be applied to colorectal cancer screening under specific conditions (weak recommendation, GRADE evidence rating: low, grade III recommended); Colon capsule endoscopic (CCE) (conditionally recommended; Very low-quality evidence).

Ultrasound colonoscopy (UCS) is recommended for early colorectal cancer_T1 (M, SM cancer) substage
.

1

Why a fine screening for coloral cancer screening is preferred

Colonoscopy is the gold standard
for colorectal cancer screening.
Endoscopic physicians can completely examine the entire colorectum under the visual lens, and the biopsy of the desirable tissue biopsy for the discovery of suspicious lesions further clarifies the pathological diagnosis, colonoscopy is a very important means of early diagnosis in colorectal cancer screening (early diagnosis), and colorectal cancer and precancerous lesions
can be confirmed by tissue biopsy.
Colonoscopy can also screen for Lynch syndrome by immunohistochemistry for mismatch repair gene (MMR) status in colorectal cancer tissues
.
For early cancer and precancerous lesions with endoscopic treatment indications, endoscopic treatment (early treatment)
can be carried out at the same time.
Therefore, colonoscopy should be preferred for colorectal cancer screening in general risk populations, or for high-risk populations with suspected colon cancer symptoms and signs
.

The results showed that the sensitivity of colorectal tumors detected ≥ 6mm by colonoscopy was 92%, the sensitivity of coloral tumors detected ≥ 10mm was 88%, and the sensitivity of colorological cancer detected was 95%-97%.

Colonoscopic screening reduced the risk of morbidity by 56% (RR 0.
44, 95% CI: 0.
22 to 0.
88) and 57% of the risk of death (RR 0.
43, 95% CI: 0.
35 to 0.
53)
compared with no screening.

In July 2018, American scholars published a paper entitled "The Impact of Colorectal Cancer Tissue Screening on Cancer Incidence and Mortality in Large Community Populations" in the journal Gastroenterology, presenting "Information on the Effectiveness of Colorectal Cancer Tissue Screening on Choice, Morbidity and Mortality in Community Populations.
"

Figure 2 Colorectal cancer screening in combination with FIT and colonoscopy reduces morbidity and mortality

The project's research methodology compares screening rates before (2000 baseline) and after the implementation of colorectal cancer tissue screening outreach in large community populations from 2007 to 2008 (primarily annual quantitative FIT screening and colonoscopy), age-adjusted annual incidence of colorectal cancer, and morbidity-based mortality
.
In eligible individuals aged 51-75 years, the annual up-to-date status of cancer screening (by quantitative FIT initial screening, colonoscopy, or sigmoidoscopy sieve), colorectal cancer incidence, cancer stage distribution, and morbidity-based mortality were
calculated.
Results: Colorectal cancer screening rate increased from 38.
9% before 2000 to 82.
7% in 2015; Early colorectal cancer detection increased and advanced coloral cancer incidence decreased by 36.
2%; Annual incidence of coloral cancer decreased by 25.
5%; The mortality rate was reduced by 52.
4%.

On March 14, 2022, the Swedish research team published a paper titled "Colorectal Cancer Screening Two Years Between One-Time Colonoscopy or Two FIT Tests: A Preliminary Report from a Randomized Controlled Trial (SCREESCO)" in the journal The Lancet Gastroenterology & Hepatology
.

Figure 3 Colorectal cancer screening: Colonoscopy is preferred for fine screening

From March 1, 2014 to December 31, 2020, the project included a total of 278,280 participants, divided into 31,140 colonoscopy groups, 60,300 quantitative FIT detection groups, and 186,840 control groups, all of whom were community residents
aged ≥ 60 years.
The primary endpoints of the study were coloral cancer incidence and mortality
.
The results of the study showed that colorectal cancer was detected in 49 cases (0.
16%) of the 31,140 cases in the colonoscopy group; Colorectal cancer
was detected in 121 (0.
20%) of the 60,300 cases in the quantitative FIT group.
Late adenoma was detected in 637 cases (2.
05%) in the colonoscopy group and 968 cases (1.
61%) in the quantitative FIT group, and the colonoscopy detection rate of precancerous lesions was 27% higher (RR 1.
27, 95% CI: 1.
15–1.
41).

The colonoscopy group found more non-advanced adenomatous disease (RR 2.
82, 95% CI: 2.
63 to 3.
02) and more right hemisoclonic lesions (i.
e.
, non-advanced adenoma, advanced adenoma, and titrulloser-like polyps)
compared with the quantitative FIT group.
Stratified analysis by sex found that colonoscopy was more likely than quantitative FIT to detect advanced adenoma in both male and female subjects (male RR 1.
27, 95% CI: 1.
12-1.
45; female RR = 1.
27, 95% CI: 1.
09-1.
49).

Coloscopy also reveals more advanced titsoridated serrated polyps located in the right hemicolon, which is more pronounced in women than in men (p=0.
009).

Preliminary results indicate that the detection rates of coloral cancer are similar and there are few
adverse events in the two screening methods.
The colonoscopy group is more likely to screen for advanced adenoma
than the quantitative FIT group.
The preliminary findings predict that the results of the study's endpoint answer the question
that colonoscopy and quantitative FIT screening can reduce colorectal cancer incidence and mortality.

Looking at the relevant research of colorectal cancer screening in China, although colonoscopy is the gold standard for colorectal cancer screening, because colonoscopy has a certain invasiveness and requires adequate intestinal preparation, it is one of the reasons for the low participation rate of
colonoscopy screening in general risk populations.
Therefore, improving residents' compliance with colonoscopy screening through cancer science education is the basic guarantee for
improving the detection rate of colorectal tumors.

2

Sigmoidoscopy

Sigmoidoscopy is also invasive and can be used for colorectal cancer screening in general risk populations, but requires less
bowel preparation.
Endoscopic physicians can descend colon, sigmoid colon and rectum through sigmoidoscopy, which has a high sensitivity and specificity for distal colororectal cancer, and European and American countries have more research on sigmoidoscopy in colorological cancer screening projects in general risk populations, and less
applied in colorological cancer screening projects in China.
The disadvantage of using sigmoidoscopy is that the whole colon, including the proximal colon (ileochal, ascending, transverse colon, etc.
), cannot be examined, so that tumors located in the proximal colon are missed
.
Therefore, there is a tendency
to be replaced by colonoscopy.

3

CTC

CT Colon imaging technique (CTC) refers to the subject's filling and expansion of the clean colon with gas after intestinal preparation, and then performing a thin CT scan of the supine and prone positions of the whole colon, three-dimensional reconstruction of the two-dimensional image, which can observe the entire colon, image the whole colon, and visualize the colon
lesions.
CTC found that the sensitivity of coloral cancer was similar to that of colonoscopy, and that the sensitivity of advanced tumors was lower than that of colonoscopy
.

A 2011 meta-analysis of general risk populations with no asymptomatic, no family history of tumors, no polyps, colorectal cancer, or inflammatory bowel disease and using CTC to screen for colorectal tumors showed that CTC detection was 80% sensitive to coloral tumors ≥ 6 mm and 88%
≥ 10 mm colorectal tumors detected.
Despite the less invasive benefits of CTC and the reduction of colorectal cancer-related mortality, there are some limitations in colorectal tumor screening in general risk populations, including the need for rigorous bowel preparation, large examination equipment, and specialized technicians
.

The results of some colorectal cancer screening programs have shown that the accuracy of colorectal adenomas or colorectal cancer detected by CTC is not high compared with colonoscopy, and tissue biopsies cannot be done for positive lesions found, and further colonoscopy and tissue biopsy are required to confirm the diagnosis
.
In terms of safety, the potential risk of radiation radiation causing tumors in CTC needs to be further explored and demonstrated
.
In addition, the cost of a CTC examination is higher, and the application in colorectal cancer screening is limited
from a cost-effective point of view.
Therefore, the Chinese Colorectal Cancer Screening and Early Diagnosis and Early Treatment Guidelines do not recommend CTC for large-scale screening of general risk populations, but only for colorectal cancer screening
under specific conditions.
The 2021 edition of the ACG guidelines states that CTC
may be used after cleansing the intestines for individuals who refuse to undergo a total colonoscopy, or where colonoscopy is contraindicated.
The CSCO Guidelines for the Diagnosis and Treatment of Colorectal Cancer (2022) states that CTC
may be an option for subjects who are unable to complete a full colonoscopy.

4

CCE

Colon capsule endoscopy (CCE) is a new non-invasive endoscopic technique
that completes colonic mucosal observation without the need for sedation, analgesia, and intestinal infusion 。 From the appearance of the ordinary capsule is similar, about 1.
5cm long, less than 1.
0cm in diameter, one end can see the black rice grain large camera, and equipped with an in vitro image recorder, the principle is that the subject through oral built-in camera and signal transmission device of the smart capsule, with the help of intestinal peristalsis to make it move in the intestine and take images, the doctor uses the image recorder and image workstation outside the body, can understand the situation of
the subject's whole colon.
The doctor only needs to play back the image taken by the CCE to make an initial diagnosis
of the colon lesion.
CCE examination is convenient, just like swallowing capsule drugs, safe and comfortable, and no pain, no trauma, no wires, no cross infection and other advantages, can eliminate the subject's fear of colonoscopy, increase the compliance of coloral cancer screening
.
Colorectal cancer screening may be used as a complementary method
for colorectal cancer screening in individuals who refuse to undergo a total colonoscopy, or who have incomplete colonoscopy, or who have contraindications to colonoscopy 。 In March 2012, the journal Endoscopy published the latest Colon capsule endoscopy: European Society of Gastrointestinal Endoscopy (ESGE) Guideline, which provides the basis
for the clinical application of CCE.
But so far, data on its studies for colorectal cancer screening have been limited
.
Current studies have shown that CCE is 58%-86% sensitive to obvious colon lesions (≥ 6 mm or 3 independent polyps >
).
It is worth noting that CCE is prone to misjudgment on the size of small polyps in the colon and has low
specificity for the diagnosis of polyps.

Since inflammatory bowel disease mostly affects the colorectal mucosa, about 70% to 80% of Crohn's disease and the vast majority of ulcerative colitis can be found in the colorectum, so CCE can be used to monitor the activity of ulcerative colitis and evaluate efficacy, but there is currently insufficient evidence to support the diagnosis of inflammatory bowel disease with CCE, and colonoscopy
is still recommended.
In addition, CCE has the following problems:

(1) CCE is unable to accurately locate
images taken along the way.
After the subject undergoes CCE examination and finds the lesion, it is difficult for the clinician to accurately locate the location of the lesion based on the images taken and the CCE working hours to accurately locate and formulate the next step of diagnosis and treatment;

(2) Intestinal preparation before CCE examination is more stringent
than colonoscopy.
Because the colonoscopy has a flushing and suction device, the residual fecal residue and fecal water
can be removed at any time during the examination.
CCE does not have this device and function, the camera is easy to be obscured by the remaining contents of the colon, and the situation that the interior of the colon is not clear or incomplete, and it is easy to miss the diagnosis;

(3) There is a risk of capsule endoscopic retention;

(4) CCE examination cannot do tissue biopsy of the positive lesions found, and tissue biopsy must be carried out by colonoscopy to confirm the diagnosis;

(5) The cost of a domestic CCE examination is significantly higher than the cost of colonoscopy, and the cost of an imported CCE examination is higher
.

Therefore, from the perspective of accessibility, safety, efficacy and cost-effectiveness, CCE is difficult to be widely used in the fine screening of colorectal cancer stratified screening
.

How can I improve the detection rate of colorectal tumors on colonoscopy?

1

How does the quality of bowel preparation affect the effectiveness of colonoscopy?

High-quality bowel preparation improves the detection and diagnosis accuracy of precancerous lesions and colorectal cancer and the safety
of endoscopic treatment.
Inadequate bowel preparation is a major obstacle to the effectiveness of colonoscopy, prolonging cecum intubation and reducing adenoma detection (ADR).

Therefore, the quality of intestinal preparation directly affects the effect
of colonoscopy.
However, most subjects are not fully aware of the importance of intestinal preparation, thinking that intestinal preparation is just drinking laxatives, and even a few subjects have a fluke mentality, even laxatives have not finished drinking to do colonoscopy, if the feces and food residues in the intestine are not clean, covering the surface of the colorectal mucosa may miss the diagnosis of colorectal lesions, or can not complete the complete colonoscopy and have to repeat the colonoscopy at a shorter interval
.

Many studies have shown that the pass rate of bowel preparation should be higher than 85%.

When the subject's bowel preparation is better, the ADR of colonoscopy is significantly higher than that of those with
insufficient bowel preparation.
The United States reported that of all colonoscopy subjects, 27%
of those who failed to prepare their intestines.

Figure 4 Effect of the quality of intestinal preparation on the effect of endoscopic diagnosis and treatment

In September 2014, the American Colorectal Cancer Multi-Society Working Group (USMSTF) published the Guidelines for Colonoscopy Bowel Preparation in the American Journal of Gastroenterology, Gastroenterology, and Digestive Endoscopic Science
.
In July 2019, the Endoscopic Physicians Branch of the Chinese Medical Doctor Association released the "Enteric Preparation Fingers Related to Gastrointestinal Endoscopic Diagnosis and Treatment in China"
.
Both U.
S.
-China guidelines recommend: use the Boston Scale or the Ottawa Scale for an assessment of the quality of bowel preparation (recommended intensity: strong; Quality of evidence: high), optimized the adequacy of colonoscopy of bowel cleansing
.

Figure 5 What a high-quality colonoscopy should require: adequate bowel preparation

2

A high-quality colonoscopy is key to ensuring the effectiveness of screening

Of all colorectal cancer cases, about 8.
2% are intercolonic carcinoma (interphase cancer) that occurs after colonoscopy, while in interphase cancer cases, about 86% are associated
with low-quality colonoscopy, insufficient visualization of the whole colon, or incomplete resection of precancerous lesions.
In addition to a good bowel readiness> rate of 85%, the currently recognized quality standards for high-quality colonoscopy have also adopted the USMSTF Colonoscopy Quality Control Recommendations (2002):

(1) In the colonoscopy report, the intestinal readiness must be described;

(2) Complete complete colonoscopy is of great significance to ensure the quality of colonoscopy, and the cecal insertion rate (CIR) is > 95%.

Studies have shown that 95% of endoscopic physicians with CIR> have a significantly lower incidence of interphase cancer in subjects than in patients examined by CIR<80% of endoscopic physicians;

(3) ADR is considered to be the main measure of the quality of mucosal examination, and it is also a recognized index for evaluating the quality of colonoscopy, which is inversely correlated
with the incidence of interphase cancer.
ADR > 25%, of which men > 25% and women > 15%.

Foreign studies have shown that for every 1% increase in ADR, the incidence of interstitial cancer will decrease by 3%;

(4) The time of withdrawal (WT) should be guaranteed at 6 min
.
Previous studies have shown significant improvements in ADR in those with WT < 6 min compared with endoscopic physicians with an average WT > of 6 min, while endoscopic physicians with a median WT of 9 min have the highest
ADR.
When colorological cancer is screened in China, WT should be guaranteed to be above
6min.

Serrated lesions account for about 30% of all colorectal cancers, and have received attention
in recent years because most of the serrated lesions are flat or unstemmed, which are usually indistinguishable from normal mucous membranes and difficult to detect 。 In May 2022, the research team at the University Medical Center Amsterdam in the Netherlands published a large-scale study entitled "The Risk of Serrated Polyp Detection and Post-Colonoscopy Interphase Cancer: A Population-Based Study" in The Lancet Gastroenterology & Hepatology, based on data from the Netherlands Colorectal Cancer Screening Project.
To assess the correlation
between proximal serrated polyp detection rate (PSPDR) as a quality indicator of colonoscopy and post-colonoscopy interphase cancer.

Figure 6 Screening for colorectal cancer: quality control and evaluation of colonoscopy

Subjects who meet the screening criteria are 55-76 years of age, and the initial screening of quantitative FIT is first passed, and those who are positive for FIT and asymptomatic are referred for colonoscopic sieve
.
More than 329,000 colonoscopies were completed from January 1, 2014 to December 31, 2020
.
During the follow-up period of 33 months with a median time after colonoscopy, 305 cases of interphase cancer
occurred.
The results showed that the three examination quality indicators related to serrated lesions, namely proximal serrated polyp detection rate (PSPDR), unstemmed serrated lesion detection rate (SSLDR), and serrated polyp detection rate (SPDR), were all negatively correlated
with interphase cancer risk 。 After analyzing the data, the research team found that the higher the PSPDR, the higher the quality of colonoscopy, and the lower the incidence of subsequent colorectal cancer, and finally selected PSPDR as the quality criterion for colonoscopy, and also found that there was a correlation between PSPDR and ADR (r=0.
59; p<0.
0001), which provided new evidence
for colonoscopy quality control.
But the value of PSPDR as a quality standard for colonoscopy needs to be further validated
for global recognition.
At present, it is generally believed that ADR is sufficient for colon cancer screening programs, and China should also use ADR as a quality standard for
colonoscopy.

How to improve the accuracy of early diagnosis of colorectal tumors?

1

Precancerous lesions and early coloral cancer are defined

Speaking of "precancerous lesions" is not unfamiliar, but it may not be clear
.
Precancerous lesions refer to certain benign lesions with cancerous potential, which are not treated for a long time and some can be turned into cancer
.
Precancerous lesions of the colorectum include advanced adenomas (villous or tubular chorioadenoma; Length diameter≥1mm; High-grade intraepithelial neoplasia), broad-based serrated lesions (serrated adenoma/polyps), polyposis (adenomatous polyposis and nonadenomatous polyposis), inflammatory bowel disease-related dysplasia, etc
.

Early colorectal cancer refers to tumors that invade the submucosal layer and are confined to or penetrate the mucosal myolayer without involvement of the innate muscle layer, including intramucosal carcinoma (M carcinoma) and submucosal carcinoma (SM carcinoma).

2

Early diagnosis of colorectal tumors

Early diagnosis of colorectal tumors refers to precancerous lesions and early-stage colorectal cancers
that are detected and confirmed by screening in asymptomatic general risk populations.
The definition of the detection rate of positive cases of colorectal tumors, that is, the detection rate of positive cases = [precancerous lesions + cancer and other rare tumors] cases / the actual number of colonoscopy × 100%; Early diagnosis rate is defined, i.
e.
early diagnosis rate = (precancerous lesions + early cancer) / (precancerous lesions + early and advanced cancers + other rare tumors) × 100%.

CSCO Guidelines (2022) Update Points: "Staging Diagnosis in Colonoscopically Confirmed Cases" revised to an L-level recommendation
.
Colonoscopy and histobiopsy pathology is not only the gold standard for early diagnosis of precancerous lesions and early colorectal cancer, but also plays an important role in the sub-stage diagnosis of stage T₁ cancer and provides a reliable basis
for endoscopic therapy indications.

Figure 7 Early colorectal cancer: mucosal cancer (M cancer stage) + submucosal cancer (SM cancer stage)

According to the literature, the indication for endoscopic therapy is M cancer; The relative indication is SM1 cancer
.
The risk of SM cancer with regional lymph node metastasis is about 15%, and endoscopic local resection does not determine the presence or absence of regional lymph node metastasis
.
To avoid incomplete early cancer resection, ultrasound colonoscopy, chest and abdominal CT
are required prior to endoscopic treatment of SM cancer.
Ultrasound colonoscopy can play an important role
in early diagnosis of cancer and TN staging diagnosis.

Figure 8 The important role of ultrasound colonoscopy in early diagnosis of early cancer and TN staging

3

Measures to improve the accuracy of early diagnosis of colorectal tumors

The public's cancer prevention and control science education and cancer screening are peers to improve the public's compliance with colorectal tumor screening
.
In the whole process of colorectal cancer screening projects, in addition to following the relevant guidelines organized by professional (association) associations, in all colonoscopy practices, continuous quality improvement measures should always be adhered to to improve the pass rate of intestinal preparation; Standardized professional training and qualification identification of colonoscopists in key positions of fine screening, normalized key assessment of CIR, ADR, WT in the quality standards of colonoscopy, and colonoscopy physicians who meet the standards are certified to work
.
Specialized training
for pathologists in the diagnosis of colorectal serrated lesions and the ability to diagnose early cancer (M, SM) stages.

epilogue

Stratified screening for colorectal cancer based on quantitative FIT primary screening and colonoscopy screening is an accessible, safe, effective, and cost-effective and feasible solution
.
Colonoscopy and tissue biopsy are the gold standard for colorectal cancer screening and early diagnosis, and there is no doubt that
colonoscopy is the first choice for colorectal cancer screening.
According to China's national conditions, in order to ensure that the "gold standard" is achieved in colorectal cancer screening, in addition to the introduction and implementation of relevant guidelines by the professional (association), it is also necessary to do a good job in the public's coloral cancer screening science education, strengthen the training, standardized assessment and colonoscopy quality assessment and control
of colonoscopy for colonoscopy doctors and pathologists.
It is indeed possible to combine quantitative FIT screening with colonoscopy sieve, and ultimately it is possible to reduce the morbidity and mortality
associated with colorectal cancer.

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Reviewer: Uni

Typography: Uni

Executive: Tourist