Diagnostic accuracy of magnifying chromoendoscopy in the assessment of tumor invasion depth in early colorectal cancer: a systematic review and meta-analysis.

PURPOSE: The aim of the study was to evaluate the ability of magnifying chromoendoscopy (MCE) to correctly differentiate early colorectal cancer (CRC) lesions with massively invasive submucosal cancer (SMm) from lesions without submucosal massive invasion (polyp, adenoma, dysplasia, intramucosal cancer, slightly invasive submucosal cancer (SMs)). METHODS: We searched PubMed, Embase, the Cochrane Library from the time of the establishment of each database to 5 April 2023. Stata 15 software was used to perform the meta-analysis for sensitivity, specificity, positive likelihood ratio (LR), and negative LR, diagnostic odds ratio, and 95% CI. A summary receiver-operating characteristic (SROC) curve was constructed, the area under the curve (AUC) was calculated, and the diagnostic value was evaluated. Furthermore, to explore the potential sources of heterogeneity, we used meta-regression to estimate the influencing factors of these studies and their impact on the diagnostic accuracy. MCE was used to evaluate the diagnostic accuracy in differentiating CRC lesions with SMm from lesions without submucosal massive invasion (polyp, adenoma, dysplasia, intramucosal cancer, SMs). Subgroup analysis was conducted as well. Deeks' funnel plots were also used to assess publication bias. RESULTS: A total of 11,387 colorectal lesions were included in 19 articles, including polyp, adenoma, dysplasia, and early cancer (intramucosal cancer, SMs, and SMm). The aggregate sensitivity, specificity, positive LR, negative LR, and diagnostic advantage scores of MCE in the diagnosis of differentiating CRC lesions with SMm from lesions without submucosal massive invasion (polyp, adenoma, dysplasia, intramucosal cancer, SMs) were 0.78 (95% CI 0.72-0.83), 0.95 (0.95% CI 0.91-0.97), 15.4 (0.95% CI 8.7-27.4), 0.23 (0.95% CI 0.18-0.30), and 66 (0.95% CI 32-136), respectively. The AUC of the SROC curve was 0.91 (0.95% CI 0.88-0.93). No significant publication bias was found with Deeks' funnel plot. The results showed significant heterogeneity due to the different objects included. CONCLUSION: MCE can differentiate CRC lesions with SMm from lesions without submucosal massive invasion (polyp, adenoma, dysplasia, intramucosal cancer, SMs) with high accuracy and it can guide assessment of invasion depth of SMm in T1 early CRCs to help us select the most appropriate treatment.

Magnifying chromoendoscopy is a reliable method in the selection of rectal neoplasms for local excision.

PURPOSE: Adequate staging of early rectal neoplasms is essential for organ-preserving treatments, but magnetic resonance imaging (MRI) frequently overestimates the stage of those lesions. We aimed to compare the ability of magnifying chromoendoscopy and MRI to select patients with early rectal neoplasms for local excision. METHODS: This retrospective study in a tertiary Western cancer center included consecutive patients evaluated by magnifying chromoendoscopy and MRI who underwent en bloc resection of nonpedunculated sessile polyps larger than 20 mm, laterally spreading tumors (LSTs) [Formula: see text] 20 mm, or depressed-type lesions of any size (Paris 0-IIc). Sensitivity, specificity, accuracy, and positive and negative predictive values of magnifying chromoendoscopy and MRI to determine which lesions were amenable to local excision (i.e., [Formula: see text] T1sm1) were calculated. RESULTS: Specificity of magnifying chromoendoscopy was 97.3% (95% CI 92.2-99.4), and accuracy was 92.7% (95% CI 86.7-96.6) for predicting invasion deeper than T1sm1 (not amenable to local excision). MRI had lower specificity (60.5%, 95% CI 43.4-76.0) and lower accuracy (58.3%, 95% CI 43.2-72.4). Magnifying chromoendoscopy incorrectly predicted invasion depth in 10.7% of the cases in which the MRI was correct, while magnifying chromoendoscopy provided a correct diagnosis in 90% of the cases in which the MRI was incorrect (p = 0.001). Overstaging occurred in 33.3% of the cases in which magnifying chromoendoscopy was incorrect and 75% of the cases in which MRI was incorrect. CONCLUSION: Magnifying chromoendoscopy is reliable for predicting invasion depth in early rectal neoplasms and selecting patients for local excision.

Thermal tissue damage caused by new endoscope model due to light absorption.

BACKGROUND AND AIM: Bright endoscopic light sources improve the visibility of the intestinal mucosa. A newly launched endoscopic system developed by Olympus Corporation (Tokyo, Japan) in 2020 required modification to prevent heat-induced tissue damage, which reportedly occurs during magnifying chromoendoscopy. We investigated the mechanism of this phenomenon by evaluating the rise in temperature of stained and unstained porcine mucosa using the new and previous endoscopic systems. METHODS: Surface temperatures of stained (India ink, 0.05% crystal violet, 0.5% methylene blue, or 0.2% indigo carmine) and unstained porcine mucosa were evaluated using infrared imaging after contact with the new endoscopic system before it was modified (system-EVIS X1; scope-GIF-EZ1500) and compared with a previous endoscopic system (system-EVIS EXERAIII; scope-GIF-H190). We performed histological analysis of the porcine mucosa stained with 0.05% crystal violet after contact with the new endoscope to evaluate the degree of tissue damage. RESULTS: Surface temperatures remained < 40°C when the new endoscope was in contact with the unstained mucosa. However, the maximum surface temperature rose to > 70°C when the new endoscope was in contact with the stained mucosa (stained other than indigo carmine). Histological analysis revealed cavity formation in porcine epithelium stained with crystal violet where the endoscope made contact for ≥ 5 s . Using the previous endoscope, the maximum surface temperature of stained mucosa remained below approximately 60°C, and the surface temperature of the unstained mucosa remained below 30°C. CONCLUSIONS: Heat transfer by light absorption could cause heat-induced tissue damage during magnifying chromoendoscopy using the new endoscope.

Depth diagnosis of early colorectal cancer: Magnifying chromoendoscopy or image enhanced endoscopy with magnification?

Depth diagnosis is extremely crucial in making a treatment choice between endoscopic resection and surgery in the early stages of cancers. Among several imaging modalities, we use magnifying endoscopy to diagnose lesions by close observation of the findings at mucosal surface layer. In combination with topical staining, magnifying endoscopy enables us to assess the definite pit structure, which referred to as magnifying chromoendoscopy (MCE). The pit pattern classification by MCE was proposed and is now widely accepted as the standard diagnostic criteria for colorectal lesions. Meanwhile, image enhanced endoscopy (IEE) represented by narrow-band imaging was developed to improve the visibility of surface and vascular findings without dyeing. Recent collaborative work performed by endoscopic experts in Japan yielded the unified diagnostic criteria, the Japan NBI Expert Team (JNET) classification, based on the findings of IEE with magnification. In this review, focusing on MCE and IEE with magnification, we aimed to give an outline of the pit pattern classification and the JNET classification, and further discuss their accuracy rate of depth diagnosis of early colorectal lesions by performing a review of the related literature. Both modalities have a high accuracy rate of nearly 90% for depth diagnosis. IEE with magnification is an ideal modality because it helps observe lesions without dye spraying; however, lesions with JNET type 2B have an inadequate diagnostic ability, which should be complemented by MCE. We conclude that accurate diagnosis is possible by examining lesions using both modalities properly to overcome the limitations of each modality.

New modality for the quantitative evaluation of tissue elasticity using a forward-viewing radial-array echoendoscope for colorectal neoplasms.

PURPOSE: Sound speed correction (SSC) is a non-invasive modality that quantifies the hardness of neoplasms. The aim of our study was to evaluate the usefulness of SSC for the diagnostic accuracy of colorectal neoplasms and to differentiate the depth of invasion. METHODS: Forty colorectal neoplasms, contributed by 40 patients, were included in the analysis. The primary outcome was the diagnostic ability of SSC for the depth of invasion of colorectal neoplasms, with the secondary endpoint being the clinical efficacy of SSC to distinguish between a neoplasm and normal mucosa. RESULTS: The median sound speeds for colorectal neoplasms and normal mucosa were 1580 m/s and 1515 m/s, respectively (p < 0.001), with a median sound speed of 1583 m/s for lesions with a depth shallower than that of the muscularis propria and 1610 m/s for depths deeper than that of the muscularis propria (p = 0.002). The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 80.0%, 100%, 100%, 83.3%, 90.0%, and 100%, respectively, for the diagnosis of neoplasms (using a cut-off sound speed of 1557 m/s) and 100%, 77.8%, 33.3%, 100%, 80.0%, respectively, for the diagnosis of the depth of invasion (using a cut-off of 1590 m/s). CONCLUSION: We identified absolute sound speeds for colorectal neoplasms and the depth of invasion of neoplasms which yielded a good diagnostic performance. SSC provides an objective evaluation of colorectal neoplasms and the depth of invasion of neoplasms and, thus, might be a useful modality in practice. TRIAL REGISTRATION: UMIN000038235 , Date of registration; October 8, 2019.

Endoscopic Ultrasound Elastography as a Novel Diagnostic Method for the Assessment of Hardness and Depth of Invasion in Colorectal Neoplasms.

INTRODUCTION: We aimed to compare the efficacy of endoscopic ultrasound elastography (EUS-EG) with that of magnifying chromoendoscopy (MCE) and endoscopic ultrasonography (EUS) for the diagnosis of the depth of invasion in colorectal neoplasms. This is an important clinical issue as the depth of invasion is associated with the risk of metastasis. METHODS: Consecutive patients with suspected superficial colorectal neoplasms, evaluated by MCE, EUS, and EUS-EG, for whom endoscopic submucosal dissection was considered, were enrolled in 2018 (derivation study) and in 2019-2020 (validation study). The primary clinical endpoint was the diagnostic yield differentiating intramucosal and shallow submucosal neoplasms from deep submucosal (dSM) and advanced colorectal cancers. In addition, inter- and intra-observer agreements of the elastic score of colorectal neoplasm (ES-CRN) were evaluated by 2 expert and 2 non-expert endoscopists. RESULTS: Thirty-one (33 lesions) and 50 (55 lesions) patients were enrolled in the derivation and validation studies, respectively. Sensitivity, specificity, positive, and negative predictive values, and accuracy of assessment of the depth of submucosal or deeper invasion in the derivation and validation groups were as follows: EUS-EG, 100/88.2/86.7/100/93.3% and 77.8/86.1/73.7/88.6/83.3%; MCE, 66.7/94.4/90.9/77.3/81.8% and 84.2/91.4/84.2/91.4/88.9%; and EUS, 93.3/77.8/77.8/93.3/84.8% and 89.5/65.7/58.6/92.0/74.1%, respectively. For the 2 expert endoscopists, interobserver agreement for the ES-CRN (first and second assessments) in the derivation group was 0.84 and 0.78, respectively; these values were 0.73 and 0.49, respectively, for the 2 non-expert endoscopists. DISCUSSION/CONCLUSION: All 3 modalities presented similar diagnostic yield. Inter- and intra-observer agreements of the ES-CRN were substantial, even for non-expert endoscopists. Therefore, EUS-EG may be a useful modality in determining the depth of invasion in colorectal neoplasms.

Anal PAP, HPV tests and magnifying chromoendoscopy with biopsies in the diagnosis of anal intraephitelial neoplasia / Papanicolau anal, testes de HPV e cromoendoscopia de ampliação com biópsias no diagnóstico de neoplasia intraepitelial anal

Abstract Introduction: Anal intraepithelial neoplasia (AIN) is the most likely precursor of squamous cells cancer which represents 90% of anal cancers. The use of biomolecular tests as a screening method has been extended by gynecology. Given the similarities that exist between the HPV disease in the lower genital tract and anorectal sectors, it is expected that HPV tests can provide information for the diagnosis, treatment and follow-up for AIN-affected patients. Objectives: Comparing the performance of anal cytology, PAP and HPV tests (Hybrid Capture and Papillocheck) against the histology of the diagnosis of low- and high-grade AIN in risk groups. Material and methods: A cross-sectional study was carried out to evaluate diagnostic methods for low- and high-grade AIN in 73 patients. Samples for anal PAP, Papillocheck and Hybrid Capture were taken from all patients who then, regardless of the results, underwent magnifying chromoendoscopy (MCE) along with biopsy. Diagnostic test performances and their 95% confidence intervals (CI: 95%) were calculated as well as the likelihood ratio for each test. Results: Of the 73 patients, 49 (67%) were women. The average age of the patients was 38 years. In 38 patients (52%), the histology was positive with 10 (14%) grade II AIN or higher. There were no statistically significant differences in sensitivity nor in specificity for low- and high-grade AINs between any of the tests. Conclusion: Anal PAP, the Hybrid Capture test (HC2, Qiagen) and PapilloCheck (Greiner Bio One) were highly sensitive but not specific for low- and high-grade AINs. Therefore, a biopsy should be conducted against a positive result of any of the tests to confirm AIN and the degree of dysplasia. The screening method selection depend on the availability but also costs of the test should be considered, since all the diagnostic tests have similar performance.

Resumo Introdução: A neoplasia intraepitelial anal é o precursor mais provável do câncer de células escamosas, que representa 90% dos tumores anais. O uso de exames biomoleculares como método de triagem foi ampliado pela ginecologia. Considerando-se as semelhanças entre as apresentações de HPV no trato genital inferior e anorretal, espera-se que os exames de HPV possam fornecer informações para o diagnóstico, tratamento e acompanhamento dos pacientes com neoplasia intraepitelial anal. Objetivo: Comparar o desempenho da citologia anal, Papanicolau, exames para HPV (teste de captura híbrida e Papillocheck) e histologia no diagnóstico de neoplasia intraepitelial anal de baixo e alto grau em grupos de risco. Material e métodos: Foi realizado um estudo transversal para avaliar métodos de diagnóstico de neoplasia intraepitelial anal de baixo e alto grau em 73 pacientes. Amostras para Papanicolau anal, Papillocheck e captura híbrida foram coletadas de todos os pacientes; independentemente dos resultados desses exames, todos foram submetidos a cromoendoscopia de ampliação (CEA) e biópsia. O desempenho dos exames e seus intervalos de confiança de 95% (95% CI) foram calculados, bem como a razão de verossimilhança para cada teste. Resultados: Dos 73 pacientes, 49 (67%) eram mulheres. A idade média dos pacientes foi de 38 anos. A histologia foi positiva em 38 pacientes (52%), dos quais dez (14%) apresentaram neoplasia intraepitelial anal grau II ou superior. Não foram observadas diferenças estatisticamente significativas na sensibilidade ou especificidade para as neoplasias intraepiteliais anal de baixo e alto grau entre qualquer um dos exames. Conclusão: O Papanicolau anal, o teste de captura híbrida (HC2, Qiagen) e o Papillocheck (Greiner Bio One) foram altamente sensíveis, mas não específicos para neoplasia intraepitelial anal de baixo e alto grau. Portanto, uma biópsia deve ser realizada após um resultado positivo em qualquer um dos testes para confirmar o diagnóstico de neoplasia intraepitelial anal e seu grau. A seleção do método de triagem depende da disponibilidade, mas os custos devem ser considerados, uma vez que todos os testes apresentam desempenho semelhante.

Usefulness of confocal laser endomicroscopy to diagnose ulcerative colitis-associated neoplasia.

Chromoendoscopy, narrow-band imaging (NBI), and confocal laser endomicroscopy (CLE) have been introduced in ulcerative colitis (UC)-associated neoplasia surveillance. We aimed to determine the ability of CLE to differentiate among UC-associated neoplasia (differentiated type or undifferentiated type), sporadic adenoma, and circumscribed regenerative lesions. Of 665 patients with UC, we carried out probe-based CLE (pCLE) on 12 patients with suspected UC-associated neoplasia in addition to magnifying chromoendoscopy with crystal violet and NBI. We compared pCLE findings with pathological diagnoses. pCLE could differentiate UC-associated differentiated cancer from other pathologies such as solitary adenoma and non-neoplastic circumscribed regenerative lesions on the basis of back-to-back orientation of crypts (P = 0.048), and UC-associated undifferentiated cancer from other pathologies on the basis of dark trabecular architecture (P = 0.015). Sensitivity, specificity, and accuracy of combination of back-to-back orientation of crypts and dark trabecular architecture for carcinoma or dysplasia were 100%, 83%, and 92%, respectively. In vivo microscopic observation with pCLE was helpful to evaluate the suspected UC-associated neoplasia.

Magnifying chromoendoscopic and endocytoscopic findings of juvenile polyps in the colon and rectum.

A precise endoscopic diagnosis is necessary for endoscopic therapy for neoplastic and non-neoplastic lesions, including juvenile polyps (JPs). Therefore, the present study aimed to clarify the characteristic endoscopic findings of JPs. A total of 154 JPs were evaluated by magnifying chromoendoscopy, 20 of which were also assessed by endocytoscopy using an ultra-high magnification endoscope. Endoscopic images were evaluated in terms of gross appearance, color, pit pattern, surface inflammatory changes and vascularity of polyps. Endocytoscopic images were evaluated with regard to the morphology of glandular cavities, nuclei of glandular cells and interstitial features. Reddish surfaces (98.1%), surface erosion (92.2%), open pits (90.3%) and low pit density (90.3%) were observed in the majority of JPs by chromoendoscopy. In addition, dilated ductal openings surrounded by normal glandular cells (100%), greater distances between gland basal layers (100%) and interstitial infiltration by inflammatory cells (100%) were observed in all JPs examined by endocytoscopy. These findings indicate that there is a tetralogy of magnifying chromoendoscopic findings characteristic of JPs: Reddish surfaces, surface erosion, open pits and low pit density. There is also a triad of endocytoscopic findings characteristic of JPs, namely dilated ductal openings surrounded by normal glandular cells, greater distances between gland basal layers, and interstitial infiltration by inflammatory cells. The aforementioned magnifying chromoendoscopic and endocytoscopic characteristics of JPs may be useful factors for diagnosing JPs.

Endoscopic submucosal dissection of multiple flat adenomas in the radiated rectum.

We report a case of multiple flat adenomas and cancer of the rectum that occurred 15 years after pelvic irradiation following surgery for uterine cancer. Adenoma borders were diagnosed accurately by magnifying chromoendoscopy, leading to their adequate excision using endoscopic submucosal dissection. This enabled minimal dissection of the irradiated pelvis that would have otherwise been difficult. Furthermore, our approach probably helped minimize loss of bowel function, thereby preserving the patient's quality of life as much as possible. Pathology of the resected specimens revealed thickened walls of the submucosal layer vessels, indicating chronic radiation proctitis. Pelvic irradiation of the bowel carries a high risk of causing flat adenomas and cancer. Close and long-term surveillance may be useful in such cases, using not only conventional colonoscopy but also chromoendoscopy with indigo carmine dye spray and magnifying endoscopy.

Magnifying chromoendoscopy combined with immunohistochemical staining for early diagnosis of gastric cancer.

AIM: To assess the diagnostic value of using magnifying chromoendoscopy combined with immunohistochemical staining of proliferating cell nuclear antigen (PCNA) and p53 in the detection of gastric precancerous lesions. METHODS: Ninety-five patients who were treated for abdominal discomfort, abdominal pain, bloating, and acid reflux at our hospital from January 2010 to December 2011 were included in the study. An ordinary gastroscopic procedure was initially performed to select the lesions. All subjects underwent magnifying chromoendoscopy to observe morphological changes of gastric pits. Biopsies were then taken from each area of interest and sent for pathological examination and detection of PCNA and p53 expression by immunohistochemistry. An immunoreactivity score for each lesion was calculated. Based on immunoreactivity scores, immunohistochemical staining was then considered. RESULTS: Compared to intestinal metaplasia, gastric pits were more diverse in size, more irregular in shape, and more disorderly in arrangement in moderate and severe dysplasia. PCNA and p53 expression was significantly higher in precancerous lesions (intestinal metaplasia and dysplasia) than in chronic gastritis. PCNA expression showed an upward trend in types A-F pits. The number of cases that showed strong PCNA positivity increased significantly with an increase in the severity of lesions. Rank sum test for independent samples showed that p53 expression was significantly higher in types E and F pits than in types A-D pits (H = 33.068, P = 0.000). Rank sum test for independent samples showed that PCNA expression was significantly higher in types E and F pits than in types A-D pits (H = 31.791, P = 0.001). CONCLUSION: The presence of types E and F pits, in which p53 and PCNA are highly expressed, is highly suggestive of the occurrence of early cancer, and patients developing these changes should be closely followed.

Diagnóstico de las lesiones neoplásicas y no-neoplásicas y predicción de la invasión submucosa del cáncer colorrectal temprano durante la colonoscopia / Diagnosis of neoplastic and non-neoplastic lesions and prediction of submucosal invasion of early cancer during colonoscopy

La cromoendoscopia de magnificación es una nueva y atractiva herramienta que permite un análisis detallado de la arquitectura morfológica de los orificios de las criptas de la mucosa. En esta revisión describimos, principalmente, la eficacia de la cromoendoscopia de magnificación y de la colonoscopia de magnificación con NBI para el diagnóstico diferencial de las lesiones colorrectales, incluyendo una distinción entre lesiones neoplásicas y no-neoplásicas y también entre cáncer temprano tratable endoscópicamente o no, basados en una revisión de la literatura. Hemos conducido un estudio prospectivo mostrando que una combinación de la colonoscopia de magnificación y la cromoendoscopia es actualmente un método más confiable que la colonoscopia convencional y la cromoendoscopia para la distinción entre lesiones neoplásicas y no-neoplásicas del colon y del recto. La colonoscopia de magnificación con NBI es tan precisa como la cromoendoscopia de magnificación. Nosotros utilizamos colonoscopia de magnificación con NBI más que la cromoendoscopia para distinguir de rutina los pólipos neoplásicos de los no-neoplásicos. Los colonoscopistas pueden predecir la profundidad de la invasión del cáncer colorrectal por medio de la cromoendoscopia de magnificación, la colonoscopia de magnificación con NBI y a través del signo de no-levantamiento. Entre estos métodos, la cromoendocopia de magnificación es el más confiable, con una exactitud, sensibilidad y especificidad de 98,8%, 85,6% y 99,4%, respectivamente. Aunque su confiabilidad depende de la habilidad del que hace la observación, la difusión de las aplicaciones de la técnica de magnificación podría influir en las indicaciones de biopsias de muestreo durante la colonoscopia y en las de mucosectomía.

Magnifying chromoendoscopy is an exciting new tool that allows detailed analysis of the morphological architecture of mucosal crypt orifices. In this review, we principally describe the efficacy of magnifying chromoendoscopy and magnifying colonoscopy with narrow band imaging (NBI) for differential diagnosis of colorectal lesions, including distinction between non-neoplastic and neoplastic lesions, and also between endoscopically treatable early invasive cancers and untreatable cancers, based on a review of the literature. We have conducted a prospective study showing that a combination of magnifying colonoscopy and chromoendoscopy is currently a more reliable method than conventional endoscopy and chromoendoscopy for separating non-neoplastic from neoplastic lesions of the colon and rectum. Magnifying colonoscopy with NBI is convenient and as accurate as chromoendoscopy with magnification. We principally use only magnifying colonoscopy with NBI, rather than chromoendoscopy, to routinely distinguish neoplastic from non-neoplastic polyps. Colonoscopists can predict the depth of invasion of early colorectal cancer by magnifying chromoendoscopy, magnifying colonoscopy with NBI and the non-lifting sign. Among these approaches, magnifying chromoendoscopy is diagnostically the most reliable, with an accuracy, sensitivity, and specificitiy of 98.8%, 85.6%, and 99.4%, respectively. Although its reliability depends on the skill of magnifying observation, widespread applications of the magnification technique could influence the indications for biopsy sampling during colonoscopy and the indications for mucosectomy.