Magnifying Chromoendoscopy and Endoscopic Ultrasonography Measure Invasion Depth of Early Stage Colorectal Cancer With Equal Accuracy on the Basis of a Prospective Trial

doi:10.1016/j.cgh.2013.06.022

Clinical Gastroenterology and Hepatology

Volume 12, Issue 4, April 2014, Pages 662-668.e2

https://doi.org/10.1016/j.cgh.2013.06.022 Get rights and content

Background & Aims

Magnifying chromoendoscopy (MC) and endoscopic ultrasonography (EUS) are used to estimate the depth of colorectal cancer (CRC) invasion, but it is not clear which procedure is more accurate. We performed a prospective study to compare MC and EUS.

Methods

A total of 70 patients with an early stage flat CRC lesion were enrolled at 6 institutions in Japan and randomly assigned to groups assessed by MC followed by EUS or EUS followed by MC. Results from MC and EUS measurements of 66 lesions were included in the final analysis. The invasion depth of each lesion was measured by each procedure and categorized as mucosal to slight submucosal (depth <1000 μm) or deep submucosal (depth ≥1000 μm); measurements were compared with the final diagnosis on the basis of the pathology analysis. All participating examiners achieved a mean κ value ≥0.6 for both MC and EUS before this trial.

Results

MC and EUS each measured the depth of lesion invasion with 71.2% accuracy (correctly for 47 of 66 lesions). MC identified lesions with deep submucosal invasion with 74.2% sensitivity and 68.6% specificity, whereas EUS identified them with 67.7% sensitivity and 74.3% specificity. The differences between MC and EUS measurements did not differ significantly. However, MC required significantly shorter observation time than EUS (361.7 ± 164.5 seconds vs 451.2 ± 209.4 seconds, P = .002).

Conclusions

MC and EUS are equally accurate in estimating the invasion depth of early stage CRC lesions. However, neither procedure has sufficient diagnostic accuracy to be used as the standard.

University Hospital Medical Network Clinical Trials Registry, Number: UMIN 000005085.

Section snippets

Patients

All patients who met all of the following inclusion criteria were prospectively enrolled in this study: (1) histologically confirmed adenocarcinoma by biopsy, including Category 4 or 5 of the Vienna classification¹⁸; (2) CRC diagnosed as early stage (within submucosal invasion) by conventional endoscopic observation; (3) flat lesions defined according to the Paris Workshop guidelines (type 0–IIa [slightly elevated], IIb [flat], IIc [slightly depressed])¹⁹; (4) tumor size ≤4 cm; (5) age 20–90

Patients

In total, 70 patients with 70 lesions were enrolled from February 2011 to December 2012 at 6 Japanese institutions, and 70 patients were randomly assigned, 36 patients to A group and 34 patients to B group. Each one lesion in both A and B groups that did not fulfill the study criteria and one lesion in B group for which observation was impossible were excluded. Moreover, one lesion in B group was excluded because histologic diagnosis of invasion depth was impossible because of the severe

Discussion

Recent technical developments such as ESD and laparoscopic surgery enable noninvasive treatment and provide many therapeutic options for CRC. Of the options, it is necessary to select an optimal therapeutic method depending on the status of each disease, and thus more accurate stage diagnosis is necessary before treatment. With respect to early CRC, because treatment differs completely depending on the presence or absence of deep submucosal invasion, it is important to distinguish M-SM_S from SM_D

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Diagnostic Value of Adding Magnifying Chromoendoscopy to Magnifying Narrow-Band Imaging Endoscopy for Colorectal Polyps
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This study examined the additional value of magnifying chromoendoscopy (MCE) on magnifying narrow-band imaging endoscopy (M-NBI) in the optical diagnosis of colorectal polyps.
A multicenter prospective study was conducted at 9 facilities in Japan and Germany. Patients with colorectal polyps scheduled for resection were included. Optical diagnosis was performed by M-NBI first, followed by MCE. Both diagnoses were made in real time. MCE was performed on all type 2B lesions classified according to the Japan NBI Expert Team classification and other lesions at the discretion of endoscopists. The diagnostic accuracy and confidence of M-NBI and MCE for colorectal cancer (CRC) with deep invasion (≥T1b) were compared on the basis of histologic findings after resection.
In total, 1173 lesions were included between February 2018 and December 2020, with 654 (5 hyperplastic polyp/sessile serrated lesion, 162 low-grade dysplasia, 403 high-grade dysplasia, 97 T1 CRCs, and 32 ≥T2 CRCs) examined using MCE after M-NBI. In the diagnostic accuracy for predicting CRC with deep invasion, sensitivity, specificity, positive predictive value, negative predictive value, and accuracy for M-NBI were 63.1%, 94.2%, 61.6%, 94.5%, and 90.2%, respectively, and for MCE they were 77.4%, 93.2%, 62.5%, 96.5%, and 91.1%, respectively. The sensitivity was significantly higher in MCE (P < .001). However, these additional values were limited to lesions with low confidence in M-NBI or the ones diagnosed as ≥T1b CRC by M-NBI.
In this multicenter prospective study, we demonstrated the additional value of MCE on M-NBI. We suggest that additional MCE be recommended for lesions with low confidence or the ones diagnosed as ≥T1b CRC. Trials registry number: UMIN000031129.
A Liquid Biopsy Assay for Noninvasive Identification of Lymph Node Metastases in T1 Colorectal Cancer
2021, Gastroenterology
We recently reported use of tissue-based transcriptomic biomarkers (microRNA [miRNA] or messenger RNA [mRNA]) for identification of lymph node metastasis (LNM) in patients with invasive submucosal colorectal cancers (T1 CRC). In this study, we translated our tissue-based biomarkers into a blood-based liquid biopsy assay for noninvasive detection of LNM in patients with high-risk T1 CRC.
We analyzed 330 specimens from patients with high-risk T1 CRC, which included 188 serum samples from 2 clinical cohorts—a training cohort (N = 46) and a validation cohort (N = 142)—and matched formalin-fixed paraffin-embedded samples (N = 142). We performed quantitative reverse-transcription polymerase chain reaction, followed by logistic regression analysis, to develop an integrated transcriptomic panel and establish a risk-stratification model combined with clinical risk factors.
We used comprehensive expression profiling of a training cohort of LNM-positive and LMN-negative serum specimens to identify an optimized transcriptomic panel of 4 miRNAs (miR-181b, miR-193b, miR-195, and miR-411) and 5 mRNAs (AMT, forkhead box A1 [FOXA1], polymeric immunoglobulin receptor [PIGR], matrix metalloproteinase 1 [MMP1], and matrix metalloproteinase 9 [MMP9]), which robustly identified patients with LNM (area under the curve [AUC], 0.86; 95% confidence interval [CI], 0.72–0.94). We validated panel performance in an independent validation cohort (AUC, 0.82; 95% CI, 0.74–0.88). Our risk-stratification model was more accurate than the panel and an independent predictor for identification of LNM (AUC, 0.90; univariate: odds ratio [OR], 37.17; 95% CI, 4.48–308.35; P < .001; multivariate: OR, 17.28; 95% CI, 1.82–164.07; P = .013). The model limited potential overtreatment to only 18% of all patients, which is dramatically superior to pathologic features that are currently used (92%).
A novel risk-stratification model for noninvasive identification of T1 CRC has the potential to avoid unnecessary operations for patients classified as high-risk by conventional risk-classification criteria.
Computer-aided diagnosis system using only white-light endoscopy for the prediction of invasion depth in colorectal cancer
2021, Gastrointestinal Endoscopy
Citation Excerpt :
Currently, NBI, M-NBI, and MCE have exhibited high accuracy in diagnosing the invasion depth of CRC and should be considered as the standard criteria. The reported accuracy for diagnosing the invasion depth of CRC was 76.4% to 98.8%.8-12,15-18 EUS has also been used to diagnose the invasion depth of CRC, and its accuracy is reported to be 89.0%.19
Endoscopic treatment is recommended for low-grade dysplasia (LGD), high-grade dysplasia (HGD), and colorectal cancer (CRC) with submucosal (SM) invasion <1000 μm. However, diagnosis of invasion depth requires experience and is often difficult. This study developed and evaluated a novel computer-aided diagnosis (CAD) system to determine whether endoscopic treatment is appropriate for colorectal lesions using only white-light endoscopy (WLE).
We extracted 3442 images from 1035 consecutive colorectal lesions (105 LGDs, 377 HGDs, 107 CRCs with SM <1000 μm, 146 CRCs with SM ≥1000 μm, and 300 advanced CRCs). All images were WLE, nonmagnified, and nonstained. We developed a novel CAD system using 2751 images; the remaining 691 images were evaluated by the CAD system as a test set. The capability of the CAD system to distinguish endoscopically treatable lesions and untreatable lesions was assessed and compared with the results from 2 trainees and 2 experts.
The CAD system distinguished endoscopically treatable from untreatable lesions with 96.7% sensitivity, 75.0% specificity, and 90.3% accuracy. These values were significantly higher than those from trainees (92.1%, 67.6%, and 84.9%; P < .01, <.01, and <.01, respectively) and were comparable with those from experts (96.5%, 72.5%, and 89.4%, respectively). Trainees assisted by the CAD system demonstrated a diagnostic capability comparable with that of experts.
The CAD system had good diagnostic capability for making treatment decisions for colorectal lesions. This system may enable a more convenient and accurate diagnosis using only WLE.
Artificial intelligence for magnifying endoscopy, endocytoscopy, and confocal laser endomicroscopy of the colorectum
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Citation Excerpt :
The authors constructed a CAD model based on a classical hand-crafted algorithm and evaluated its performance using 121 images from 121 lesions. Its achieved 84% sensitivity and 83% specificity in discriminating SM-m, which were considered excellent values given even expert endoscopists reportedly achieve only 74% sensitivity and 69% specificity in identifying such lesions [21]. Recently, 2 research teams conducted retrospective studies on newly developed CAD systems based on a deep-learning (convolutional neural network) algorithm.
Because magnifying endoscopy is considered to be more accurate at predicting the histology of colorectal polyps than nonmagnifying endoscopy, it has been attracting a lot of attention, especially in Japan. However, use of magnifying endoscopy is not yet widespread because of its limited availability and the difficulty in interpreting the acquired images. Application of artificial intelligence (AI) is now changing this situation because it helps less-skilled endoscopists to accurately interpret magnified images. Research in this field initially focused on magnifying endoscopy with narrow-band imaging as the target of AI. Most previously published retrospective studies have reported over 90% sensitivity in differentiation of neoplastic lesions; however, automatically indicating the region of interest (ROI) of the polyps that AI should analyze has been found to be challenging. To address this practical problem, some researchers have started to adopt contact endomicroscopy as a target for AI. Contact endomicroscopy includes endocytoscopy (520-fold magnification, Olympus, Tokyo, Japan) and confocal laser endomicroscopy (1000-fold magnification, Mauna Kea, Paris, France). These forms of contact endomicroscopy provide ultramagnified images that make it unnecessary to manually select the ROI because the entire image acquired by contact endomicroscopy is the ROI of the targeted polyps. This strength of contact endomicroscopy has contributed to early implementation of this technology into clinical practice, which may change the utility of magnifying endoscopy in clinical settings and help increase its use globally in the near future.
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: Conflicts of interest The authors disclose no conflicts.

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Original articleAlimentary tractMagnifying Chromoendoscopy and Endoscopic Ultrasonography Measure Invasion Depth of Early Stage Colorectal Cancer With Equal Accuracy on the Basis of a Prospective Trial

Background & Aims

Methods

Results

Conclusions

Section snippets

Patients

Patients

Discussion

Gastrointest Endosc

Clin Gastroenterol Hepatol

Gastrointest Endosc

Gastrointest Endosc

Gastrointest Endosc

Gastrointest Endosc

Gastrointest Endosc

Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008

Int J Cancer

Correlations between lymph node metastasis and depth of submucosal invasion in submucosal invasive colorectal carcinoma: a Japanese collaborative study

J Gastroenterol

Japanese Society for Cancer of the Colon and Rectum (JSCCR) guidelines 2010 for the treatment of colorectal cancer

Int J Clin Oncol

Evaluation of endoscopic ultrasonography in colorectal villous lesions

Int J Colorectal Dis

Role of endoscopy in staging colorectal cancer

Semin Surg Oncol

Usefulness of the high-frequency ultrasound probe in pretherapeutic staging of superficial-type colorectal tumors

Int J Oncol

Pit pattern in colorectal neoplasia: endoscopic magnifying view

Endoscopy

Assessment of colorectal lesions using magnifying colonoscopy and mucosal dye spraying: can significant lesions be distinguished?

Endoscopy

Original article
Alimentary tract
Magnifying Chromoendoscopy and Endoscopic Ultrasonography Measure Invasion Depth of Early Stage Colorectal Cancer With Equal Accuracy on the Basis of a Prospective Trial