Search

Background and Aims: The therapeutic outcome of endoscopic submucosal dissection (ESD) for large protruding tumors has not yet been evaluated. We aimed to compare the outcomes of ESD in protruding tumors with those of laterally spreading tumors (LSTs).Methods: Endoscopic submucosal dissection was attempted in 218 patients with 220 colorectal tumors ≥30 mm in diameter (67, protruding tumors; 153, LSTs) from July 2007 to June 2014. We retrospectively reviewed patient medical records, therapeutic outcomes, and procedure-related adverse events. This study defined lesions with a height of 10 mm or more as protruding tumors and those with a height under 10 mm as LSTs.Results: The mean lesion diameter, height, and volume were 43.8, 9.5 mm, and 13.6 cm(3), respectively. The mean procedure time was 75.5 min. Deep submucosal cancer was more frequent in protruding tumors than in LSTs (11.9 vs. 2.6%, P = 0.005). Severe fibrosis was more common in protruding tumors than in LSTs (19.4 vs. 3.9%, P < 0.001). En bloc resection and complete resection rates were lower in protruding tumors than in LSTs (en bloc resection, 76.1 vs. 92.8%, P = 0.001; complete resection, 64.2 vs. 79.1%, P = 0.020). Intra- and post-procedural bleeding were more frequent in protruding tumors than in LSTs (22.4 vs. 2.6%, P < 0.001; 6.0 vs. 0.7%, P = 0.031, respectively). By multivariate analysis, protruding tumor morphology (odds ratio 1.919, P = 0.048) and tumor size ≥60 mm (odds ratio 2.490, P = 0.030) were associated with incomplete resection.Conclusions: Endoscopic submucosal dissection for protruding tumors is less effective than ESD for LSTs, with lower rate of complete resection occurring with protruding tumors. [ABSTRACT FROM AUTHOR]

Background and Aims: 15-Hydroxprostaglandin dehydrogenase (15-PGDH) mediates a colon neoplasia suppressor pathway, acting through metabolic antagonism of cyclooxygenase-mediated colon carcinogenesis. To determine whether the colon tumor prevention activity of 15-PGDH acts as a constant or variable effect among individuals, we determined whether 15-PGDH levels remain stable over subsite and time in the human colon, determined the extent of differences in 15-PGDH levels between different individuals, and determined whether 15-PGDH modulation mediates any part of the anti-colon tumor effect of aspirin. Methods: Using real-time PCR, we measured 15-PGDH mRNA to determine the correlation of 15-PGDH level in replicate colon biopsies, in biopsies from throughout the length of the colon, in repeat biopsies taken 4 months apart, and in paired biopsies of individuals taken before and after aspirin treatment, and by Western-blot for 15-PGDH protein in mice. Results: Colonic 15-PGDH levels varied 4.4-fold across the human population. Within individuals, 15-PGDH levels proved highly reproducible ( r = 0.81 in duplicate biopsies) and stable along the length of the colon, with average 15-PGDH levels deviating by only 17 % from rectum to cecum. An individual's 15-PGDH levels are also highly stable over time, with a median coefficient of variation over a 4-month interval of only 12 %. Last, colonic 15-PGDH levels proved resistant to alteration by aspirin, with only a 10 % difference in 15-PGDH levels measured before and after aspirin treatment. Conclusions: 15-PGDH levels vary across the population in a stable and reproducible manner, and are resistant to alteration by aspirin. 15-PGDH represents an independent target for modulation by candidate colon tumor chemopreventive agents. [ABSTRACT FROM AUTHOR]

Indocyanine green (ICG) has been used in clinical practice for more than 40 years and its safety and preferential accumulation in tumors has been reported for various tumor types, including colon cancer. However, reports on clinical assessments of ICG-based molecular endoscopy imaging for precancerous lesions are scarce. We determined visualization ability of ICG fluorescence endoscopy in colitis-associated colon cancer using 30 lesions from an azoxymethane/dextran sulfate sodium (AOM/DSS) mouse model and 16 colon cancer patient tissue-samples. With a total of 60 images (optical, fluorescence) obtained during endoscopy observation of mouse colon cancer, we used deep learning network to predict four classes (Normal, Dysplasia, Adenoma, and Carcinoma) of colorectal cancer development. ICG could detect 100% of carcinoma, 90% of adenoma, and 57% of dysplasia, with little background signal at 30 min after injection via real-time fluorescence endoscopy. Correlation analysis with immunohistochemistry revealed a positive correlation of ICG with inducible nitric oxide synthase (iNOS; r > 0.5). Increased expression of iNOS resulted in increased levels of cellular nitric oxide in cancer cells compared to that in normal cells, which was related to the inhibition of drug efflux via the ABCB1 transporter down-regulation resulting in delayed retention of intracellular ICG. With artificial intelligence training, the accuracy of image classification into four classes using data sets, such as fluorescence, optical, and fluorescence/optical images was assessed. Fluorescence images obtained the highest accuracy (AUC of 0.8125) than optical and fluorescence/optical images (AUC of 0.75 and 0.6667, respectively). These findings highlight the clinical feasibility of ICG as a detector of precancerous lesions in real-time fluorescence endoscopy with artificial intelligence training and suggest that the mechanism of ICG retention in cancer cells is related to intracellular nitric oxide concentration. [ABSTRACT FROM AUTHOR]

We aimed to develop a computer-aided diagnostic system (CAD) for predicting colorectal polyp histology using deep-learning technology and to validate its performance. Near-focus narrow-band imaging (NBI) pictures of colorectal polyps were retrieved from the database of our institution. Of these, 12480 image patches of 624 polyps were used as a training set to develop the CAD. The CAD performance was validated with two test datasets of 545 polyps. Polyps were classified into three histological groups: serrated polyp (SP), benign adenoma (BA)/mucosal or superficial submucosal cancer (MSMC), and deep submucosal cancer (DSMC). The overall kappa value measuring the agreement between the true polyp histology and the expected histology by the CAD was 0.614–0.642, which was higher than that of trainees (n = 6, endoscopists with experience of 100 NBI colonoscopies in <6 months; 0.368–0.401) and almost comparable with that of the experts (n = 3, endoscopists with experience of 2,500 NBI colonoscopies in ≥5 years) (0.649–0.735). The areas under the receiver operating curves for CAD were 0.93–0.95, 0.86–0.89, and 0.89–0.91 for SP, BA/MSMC, and DSMC, respectively. The overall diagnostic accuracy of the CAD was 81.3–82.4%, which was significantly higher than that of the trainees (63.8–71.8%, P < 0.01) and comparable with that of experts (82.4–87.3%). The kappa value and diagnostic accuracies of the trainees improved with CAD assistance: that is, the kappa value increased from 0.368 to 0.655, and the overall diagnostic accuracy increased from 63.8–71.8% to 82.7–84.2%. CAD using a deep-learning model can accurately assess polyp histology and may facilitate the diagnosis of colorectal polyps by endoscopists. [ABSTRACT FROM AUTHOR]

Purpose: We aimed to evaluate the recurrence rate of colorectal neoplasia showing histologic lateral margin involvement after en bloc endoscopic submucosal dissection (ESD).Methods: We reviewed 527 colorectal lesions that were removed by en bloc ESD from 2005 to 2013 and followed by endoscopy. Based on the postprocedural pathologic reports, the lesions were categorized as follows: lesions with clear deep and positive lateral margins (n = 63) and lesions with R0 resection (n = 299).Results: The tumor size was 45.7 ± 21.1 mm in the lateral margin-positive group and 30.6 ± 15.1 in the R0 group (P < 0.001). Procedure time was longer in the lateral margin-positive group than in the R0 group (94.3 ± 75.1 vs. 54.1 ± 48.9 min; P < 0.001). Lateral margin positivity was associated with ESD time ≥ 120 min in the multivariate analysis. Compared with 0-I morphology, LST-G was significantly associated with the lateral margin positivity. The volume of ESD experience in endoscopists may also be associated with the lateral margin positivity. Histologic reassessment of the specimen suggested that 32.2% of lateral margin-positive cases based on the initial pathology report were false-positive lateral margin involvement. The 5-year cumulative recurrence rate was 0.6% in the R0 group and 5% in the margin-positive group (P = 0.198).Conclusions: The local recurrence rate was not higher in lateral margin-positive cases than in R0 resection cases if the colorectal epithelial neoplasia was removed in an en bloc manner using ESD. Meticulous pathologic interpretation may reduce unnecessarily frequent surveillance after en bloc ESD. [ABSTRACT FROM AUTHOR]

Background and Aim Bleeding is the most common adverse event following colonoscopic endoscopic mucosal resection (EMR). We aimed to assess the clinical outcomes of a colon EMR according to the post-EMR ulcer status and determine the risk factors of delayed postpolypectomy bleeding (DPPB) based on the post-EMR ulcer status. Methods The medical records and endoscopic images of patients who underwent EMR of colon polyps with diameters of ≥ 5 mm were retrospectively reviewed by us. If any exposed vessels were observed on the post-EMR ulcer, the types of exposed vessels were classified into cut and uncut vessels. The coagulation injuries on the post-EMR ulcer were categorized as grades 1, 2, or 3. Results In total, 505 patients with 728 polyps were examined. Exposed vessels were present in 416 post-EMR ulcers, including cut vessels in 11 (1.5%) and uncut vessels in 405 (55.6%). With regard to coagulation injury, 113 (15.5%), 443 (60.9%), and 172 (23.6%) post-EMR ulcers had grades 1, 2, and 3 injuries, respectively. DPPB was observed in 20 lesions (2.7%). Multivariate analysis indicated that a polyp size > 10 mm (odds ratio [OR], 3.354; 95% confidence interval [CI], 1.229-9.154), cut vessels (OR, 18.913; 95% CI, 3.106-115.187), and grade 3 coagulation injury (OR, 16.796; 95% CI, 1.825-154.556) were associated with DPPB. Conclusions Cut vessels and severe coagulation injury on post-EMR ulcers, as well as larger polyp size, are risk factors for DPPB. Careful inspection of post-EMR ulcers and prophylactic hemostasis, if necessary, may improve the clinical outcomes of colonoscopic EMR. [ABSTRACT FROM AUTHOR]

Background Colorectal cancer (CRC) has been known to complicate Crohn’s disease (CD). Several reports in Western population revealed that CRC in CD were characterized by much younger onset and equal distribution of tumors along the entire colon. However, clinicopathologic features of CD-associated CRC in Korean population have not been well documented yet. Methods Among 2968 Korean CD patients, 16 patients (0.54%) were found to develop CRC during follow up. We reviewed clinicopathologic features of the 16 CRC patients. Results The mean age at the time of CRC diagnosis was 39.3 years (range 18–59 years) and 14 of the 16 CRCs (87.5%) occurred in anorectal region. Mucinous adenocarcinoma was strikingly frequent (9/16, 56.3%) and eight cases (8/9) of the mucinous adenocarcinoma cases were located at anorectal area. The other cases consisted of 4 tubular adenocarcinomas, 2 signet ring cell carcinomas and 1 neuroendocrine tumor. Thirteen patients (81.3%) had a history of perianal fistula and 8 of them had a histological association between the CRC and the perianal fistula. Conclusions CD-associated CRC was characterized by young age at diagnosis, mucinous histology and association with perianal fistula in Korean patients. [ABSTRACT FROM AUTHOR]

Background and Aim We aimed to investigate the ability of fluoro-2-deoxy- d-glucose (FDG) positron emission tomography (PET)/computed tomography (CT) to detect synchronous neoplasms, specifically obstructive colorectal cancer (CRC) and CRC in the proximal colon and to suggest a management strategy based on FDG PET/CT findings. Methods From the CRC surgery database of our institution, 518 patients with obstructive CRC whose proximal colon could not be examined by colonoscopy and who underwent preoperative FDG PET/CT were eligible for this study. Of these, final analyses were performed in 345 patients who had reference standards for the proximal colon, which were a surgical colectomy specimen and/or postsurgical colonoscopy. The per-patient and per-lesion performances of FDG PET/CT for synchronous CRC diagnosis were determined. Results Of 345 patients, 14 (4.1%) had 14 proximal synchronous CRCs. Thirty-four patients showed 39 areas of abnormal FDG uptake on PET/CT in the colon proximal to the obstructive CRC. PET/CT detected all of the 14 proximal synchronous CRCs. The per-patient PET/CT sensitivity, specificity, positive predictive value, and negative predictive value for proximal synchronous CRC were 100%, 93.9%, 41.2%, and 100%, respectively. Per-lesion values were 100%, 92.6%, 35.9%, and 100%, respectively. The per-lesion sensitivity and negative predictive value of PET/CT for advanced adenoma were 45.5% and 92.7%, respectively. Conclusions The FDG PET/CT shows a high sensitivity and negative predictive value for the detection of proximal synchronous CRC in patients with obstructive CRC, enabling negative findings in the proximal colon on PET/CT to definitively exclude proximal synchronous CRC. Preoperative PET/CT recommended to determine the proper surgical plan in patients with obstructive CRC. [ABSTRACT FROM AUTHOR]

Western-style diet (WD) and dysbiosis are known to be associated with colonic inflammation, which contributes to carcinogenesis. Metformin (Met) exerts anti-inflammatory effects to induce AMP-activated protein kinase (AMPK), resulting in suppressed protein synthesis and reduced cell proliferation. Probiotic VSL#3 (V) modifies microbial composition. We investigated the chemopreventive mechanisms of Met and V in WD-induced colitis-associated colon carcinogenesis. Male BALB/c mice were randomly divided into five groups: a control diet (CD) group, WD group, WD+ Met (250 mg/kg/day) group, WD+V (1.3 million bacteria/day) group, and WD+Met+V group. All mice were exposed to azoxymethane (10 mg/kg) followed by 2% dextran sodium sulfate (DSS) for 7 days. Using HCT-116 human colon cancer cell line, expression of AMPK, extracellular signal-regulated kinase ( ERK), cyclin D1, and Bcl-2 was investigated and cell cycle arrest was assessed. WD enhanced the severity of colitis and tumor growth compared with CD. The combination of Met and V significantly ameliorated colitis and tumor growth by inhibiting macrophage infiltration and maintaining epithelial integrity. In vitro assays showed that the combination therapy promoted late apoptosis by inhibiting cyclin D1 and Bcl-2 and activating pro-apoptotic ERK. A combination therapy with Met and V attenuates tumor growth in a mouse model of WD-induced colitic cancer, suggesting that this strategy could be useful for the chemoprevention of colon cancer. [ABSTRACT FROM AUTHOR]

Objectives. To investigate the optimal cut-off of the maximum standard uptake value (SUVmax) for the detection of colorectal neoplasms and to suggest those for whom further colonoscopy is recommended among patients with incidental colonic uptake on positron emission tomography-computed tomography (PET-CT). Materials and methods. In 306 patients who underwent colonoscopy within 3 months of receiving PET-CT between January and December 2009, measurements of the per-patient and per-lesion diagnostic performance of PET-CT for the detection of colonic neoplasms were obtained. Receiver operating characteristic (ROC) analysis was used to identify the SUVmax that provided a high probability of diagnosing malignancy and high-grade dysplasia. Results. The per-patient and per-lesion PET-CT detection sensitivities for malignancies were 93.3% (28/30; 95% confidence interval (CI) 76.5% to 98.9%) and 93.5% (29/31, 95% CI 77.2% to 98.9%), respectively; the sensitivities for high-grade dysplasia were both 90.0% (9/10; 95% CI 54.1% to 99.5%). As a criterion to specifically detect both malignancy and high-grade dysplasia on focal uptake, a SUVmax greater than 2.5 yielded a 92.3% per-lesion sensitivity and a 42.9% per-lesion positive predictive value (PPV). In the ROC curve analysis, a cut-off value of SUVmax = 5.8 was established, at which the sensitivity, PPV and positive likelihood ratio for diagnosing malignancy and high-grade dysplasia were 71.8% (28/39; 95% CI 54.9% to 84.5%), 84.8% (28/33; 95% CI 67.3% to 94.3%) and 6.9, respectively. Conclusion. The optimal cut-off value to identify a malignancy or high-grade dysplasia was SUVmax = 5.8. However, to avoid missing a malignancy or high-grade dysplasia, a colonoscopy should be performed above a SUVmax = 2.5. [ABSTRACT FROM AUTHOR]

Background: Early and accurate detection of adenomatous colonic polyps is a major concern in the prevention of colon cancer. Near-infrared fluorescence (NIRF) imaging with optical probes targeting specific peptides enables the noninvasive visualization and characterization of lesions. Matrix metalloproteinases (MMPs) are known to play an important role in tumorigenesis and tumor progression.Aim: To investigate the effectiveness of NIRF imaging, with a novel MMP-activatable probe based on a polymeric nanoparticle platform, in the colon cancer models.Methods: We used an azoxymethane (AOM)-induced mouse colon cancer model resembling human sporadic colon cancer and an MMP-positive xenograft tumor model. MMP expression was evaluated by Western blotting, real-time PCR, and immunohistochemical staining. NIRF imaging was performed with a novel MMP-activatable probe, an MMP-inactivatable probe, and saline. In addition, we observed the change of NIRF signal intensity after intratumoral administration of an MMP-inhibitor.Results: Multiple tumors with various sizes developed in AOM-treated mouse colons, progressing from adenomas to adenocarcinomas, with MMP expression progressively increasing in the normal-adenoma-adenocarcinoma sequence. In mice injected with the MMP-activatable probe, the NIRF signal also increased in this sequence and was highly correlated with MMP expression (p < 0.001). Tumor-background-ratios (TBR) of adenocarcinoma to adjacent normal mucosa by a novel probe were significantly higher than that of adenoma (p < 0.001). In both the AOM and xenograft models, NIRF signals of tumors decreased after treatment with an MMP-inhibitor.Conclusions: NIRF imaging using a polymeric nanoparticle-based probe may be useful for detecting early stage disease and for assessing treatment response. [ABSTRACT FROM AUTHOR]