Long-term prognosis after endoscopic submucosal dissection for colorectal tumors in patients aged over 80 years.

BACKGROUND: In Japan, endoscopic submucosal dissection (ESD) is standardized for large colorectal tumors. However, its validity in the elderly population is unclear. We aimed to evaluate the safety and efficacy of ESD for colorectal tumors in elderly patients aged over 80 years. METHODS: ESD was performed on 178 tumors in 165 consecutive patients aged over 80 years between December 2008 and December 2018. We retrospectively evaluated the clinicopathological characteristics and clinical outcomes of ESD. We also assessed the prognosis of 160 patients followed up for more than 12 months. RESULTS: The mean patient age was 83.7 ± 3.1 years. The number of patients with comorbidities was 100 (62.5%). Among all patients, 106 (64.2%) were categorized as class 1 or 2 according to the American Society of Anesthesiologists classification of physical status (ASA-PS), and 59 (35.8%) were classified as class 3. The mean procedure time was 97.7 ± 79.3 min. The rate of histological en bloc resection was 93.8% (167/178). Delayed bleeding in 11 cases (6.2%) and perforation in 7 cases (3.9%) were treated conservatively. The 5-year survival rate was 89.9%. No deaths from primary disease (mean follow-up time: 35.3 ± 27.5 months) were observed. Overall survival rates were significantly lower in the non-curative resection group that did not undergo additional surgery than in the curative resection group (P = 0.0152) and non-curative group that underwent additional surgery (P = 0.0259). Overall survival rates were higher for ASA-PS class 1 or 2 patients than class 3 patients (P = 0.0105). Metachronous tumors (> 5 mm) developed in 9.4% of patients. CONCLUSIONS: ESD for colorectal tumors in patients aged over 80 years is safe. Colorectal cancer-associated deaths were prevented although comorbidities pose a high risk of poor prognosis.

Effect of educational lecture on the diagnostic accuracy of Japan NBI Expert Team classification for colorectal lesions.

BACKGROUND: An educational and training program is required for generalization of Japan NBI Expert Team (JNET) classification. However, there is no detailed report on the learning curve of the diagnostic accuracy of endoscopists using JNET classification. We examined the effect of an educational lecture on beginners and less experienced endoscopists for improving their diagnostic accuracy of colorectal lesions by JNET classification. METHODS: Seven beginners with no endoscopy experience (NEE group), 7 less experienced endoscopists (LEE group), and 3 highly experienced endoscopists (HEE group) performed diagnosis using JNET classification for randomized NBI images of colorectal lesions from 180 cases (Type 1: 22 cases, Type 2A: 105 cases, Type 2B: 33 cases, and Type 3: 20 cases). Next, the NEE and LEE groups received a lecture on JNET classification, and all 3 groups repeated the diagnostic process. We compared the correct diagnosis rate and interobserver agreement before and after the lecture comprehensively and for each JNET type. RESULTS: In the HEE group, the correct diagnosis rate was more than 90% with good interobserver agreements (kappa value: 0.78-0.85). In the NEE and LEE groups, the correct diagnosis rate (NEE: 60.2 → 68.0%, P < 0.01; LEE: 66.4 → 86.7%, P < 0.01), high-confidence correct diagnosis rate (NEE: 19.6 → 37.2%, P < 0.01; LEE: 43.6 → 61.1%, P < 0.01), and interobserver agreement (kappa value, NEE: 0.32 → 0.43; LEE: 0.39 → 0.75) improved after the lecture. In the examination by each JNET type, the specificity and positive predictive value in the NEE and LEE groups generally improved after the lecture. CONCLUSION: After conducting an appropriate lecture, the diagnostic ability using JNET classification was improved in beginners or endoscopists with less experience in NBI magnifying endoscopy.

Clinical usefulness of linked color imaging for evaluation of endoscopic activity and prediction of relapse in ulcerative colitis.

PURPOSE: In the treatment of ulcerative colitis (UC), accurate evaluation of UC activity is important to achieve mucosal healing. We sought to investigate the clinical utility of linked color imaging (LCI) for the evaluation of endoscopic activity and prediction of relapse in UC patients. METHODS: We enrolled 72 consecutive UC patients in remission who underwent colonoscopy at our institution between September 2016 and October 2018. The relationship between the presence of redness in white light imaging (WLI) and LCI and histopathological inflammation (Geboes score: GS) at 238 biopsy sites was examined. We also assessed the presence or absence of planar redness in the entire rectum as ± and classified the patients into three groups according to the combination of WLI/LCI: A: WLI-/LCI-, B: WLI-/LCI+, and C: WLI+/LCI+. The relationship between WLI/LCI classification and relapse in 64 patients followed up for more than 12 months from initial colonoscopy was assessed and compared to the Mayo endoscopic subscore (MES). RESULTS: A GS of 0 or 1 accounted for 89% of WLI/LCI non-redness sites, while a GS of 2 or 3 accounted for 42% of WLI non-redness/LCI redness sites. LCI findings were significantly correlated with GS. During follow-up, 10 patients in group C and four patients in group B relapsed, but none in group A. Non-relapse rates were significantly correlated with WLI/LCI classification, but not with MES. CONCLUSION: LCI is a useful modality for accurate assessment of endoscopic activity and prediction of relapse in UC by detecting mild inflammation unrecognizable by WLI.

Long-Term Outcomes after Endoscopic Submucosal Dissection for Ulcerative Colitis-Associated Dysplasia.

INTRODUCTION: The Surveillance for Colorectal Endoscopic Neoplasia Detection and Management in Inflammatory Bowel Disease Patients: International Consensus Recommendations guidelines recommend surveillance colonoscopy instead of colectomy after the complete removal of "endoscopically resectable" dysplastic lesions in ulcerative colitis (UC). There are no studies on long-term outcomes of endoscopic submucosal dissection (ESD) for UC-associated neoplasia (UCAN). We aimed to evaluate the clinical outcomes of ESD for UC-associated dysplasia (UCAD) during long-term follow-up. METHODS: We retrospectively enrolled 17 consecutive UC patients with 22 UCADs, who underwent initial ESD or total proctocolectomy at the Hiroshima University Hospital. The clinicopathological features of the patients and neoplasias and clinical outcomes of ESD were evaluated and compared with those of total proctocolectomy. RESULTS: UCAD in the ESD and total proctocolectomy groups was mostly noted on the left side of the colon, and most lesions were superficial macroscopic lesions. In the ESD group, en bloc resection and histological complete resection rates were 83 and 67%, respectively. One patient died of malignant melanoma; however, none of the patients died of UC-associated carcinoma in both groups. Metachronous neoplasias developed in 5 of the 7 patients in the ESD group. Among the 5 patients with metachronous UCAN, 4 finally underwent total proctocolectomy and 1 underwent additional ESD. CONCLUSIONS: ESD for UCAD is a useful method for total excisional biopsy. UC patients with UCAD resected by ESD have a high risk of developing metachronous UCAN during the follow-up period.

Dual Red Imaging Maintains Clear Visibility During Colorectal Endoscopic Submucosal Dissection.

BACKGROUND: The endoscopic lens becomes clouded and its visibility reduces during colorectal endoscopic submucosal dissection (ESD), especially in cases with submucosal fatty tissue. Dual red imaging (DRI) is a novel image-enhanced endoscopic technique that improves endoscopic visibility. AIMS: This study aimed to evaluate the predictive factors of submucosal fatty tissue and the clinical usefulness of DRI in maintaining clear visibility during colorectal ESD. METHODS: The study participants included 586 consecutive patients with 645 colorectal tumors who underwent ESD between January 2014 and July 2017. First, the degree of submucosal fatty tissue was evaluated by reviewing recorded images, and the clinical characteristics of the patients and tumors related to severe submucosal fatty tissue were evaluated. Second, 34 tumors resected using DRI were propensity score-matched in a 1:1 ratio to other resected tumors using white light imaging (WLI), and the degree of endoscope lens cloudiness and clinical outcomes were evaluated. RESULTS: The proportion of tumors located in the right side of the colon, body mass index (≥ 25, BMI), and hemoglobin A1c (≥ 6.5%, HbA1c) were significantly higher in patients with severe submucosal fatty tissue. The visibility in the DRI group was significantly better than in the WLI group. Treatment outcomes in the DRI group were as good as those in the WLI group. CONCLUSIONS: Tumor location in the right side of the colon, BMI (≥ 25), and HbA1c (≥ 6.5%) are the predictive factors of severe submucosal fatty tissue. DRI is useful in maintaining clear visibility during colorectal ESD, especially with submucosal fatty tissue.

Autopsy of anaplastic carcinoma of the pancreas producing granulocyte colony-stimulating factor.

A 50-year-old man presented to a nearby hospital with high fever and anorexia. An abdominal tumor was detected, and he was referred to our hospital. A pancreatic tumor was detected by computed tomography and abdominal ultrasonography. He had high fever, leukocytosis, and high serum granulocyte colony-stimulating factor (G-CSF). We performed a tumor biopsy and histological examination revealed anaplastic carcinoma of the pancreas. Based on the diagnosis, we initiated chemotherapy using gemcitabine plus S-1. However, the tumor rapidly progressed and he deteriorated and died 123 days after admission. As immunohistochemical study showed positive staining for G-CSF in the tumor cell, we diagnosed the tumor producing G-CSF during autopsy. Anaplastic carcinoma of the pancreas producing G-CSF is very rare, with 10 cases, including ours, reported in the literature.

Multi-response gelation based on the molecular assembly of Sudan I dye derivatives for phase selective gelators and chemosensors.

Sudan I dye-based smart low molecular weight gelators with/without a perfluoroalkyl group have been successfully synthesized and characterized by rheological measurements, scanning electron microscopy (SEM), IR, and NMR spectroscopies. The gelation behaviors in response to temperature, pH changes, metal cations, and UV-vis light irradiation are investigated. Compounds 1 and 2 could selectively sense the Cu2+ cation in the presence of other metal cations. Moreover, compound 2 with a perfluoroalkyl group shows phase selective gelation ability. This work also provides a valuable reference for exploiting photosensitive materials as chemosensors.

Magnetic Field Alignment, a Perspective in the Engineering of Collagen-Silica Composite Biomaterials.

Major progress in the field of regenerative medicine is expected from the design of artificial scaffolds that mimic both the structural and functional properties of the ECM. The bionanocomposites approach is particularly well fitted to meet this challenge as it can combine ECM-based matrices and colloidal carriers of biological cues that regulate cell behavior. Here we have prepared bionanocomposites under high magnetic field from tilapia fish scale collagen and multifunctional silica nanoparticles (SiNPs). We show that scaffolding cues (collagen), multiple display of signaling peptides (SiNPs) and control over the global structuration (magnetic field) can be combined into a unique bionanocomposite for the engineering of biomaterials with improved cell performances.

Erratum: Debons et al. Magnetic Field Alignment, a Perspective in the Engineering of Collagen-Silica Composite Biomaterials. Biomolecules 2021, 11, 749.

In the original article, there was a mistake published in Figure 2 [...].

Genomic Landscape of Early-stage Colorectal Neoplasia Developing From the Ulcerative Colitis Mucosa in the Japanese Population.

BACKGROUNDS: Colorectal neoplasias (CRN)s developing from the ulcerative colitis (UC) mucosa include both colitic and sporadic neoplasias. Although several genomic analyses of advanced colitis-associated cancer are available, such studies do not distinguish between colitic and sporadic cases, and the early-stage genomic alterations involved in the onset of colitic cancer remain unclear. To address this, we performed a genomic analysis of early-stage CRN developing from the UC mucosa (CRNUC). METHODS: We extracted DNA from 36 early-stage CRNUCs (T1 cancer, 10; dysplasia, 26) from 32 UC patients and performed targeted sequencing of 43 genes commonly associated with colitis-associated cancer and compared the results with sequencing data from the Japanese invasive colitis-associated cancer. RESULTS: The most frequently mutated gene in the CRNUC cohort was APC (mutated in 47.2% of the cases), followed by TP53 (44.4%), KRAS (27.8%), and PRKDC (27.8%). None of the TP53 mutations occurred at any of the hotspot codons. Although the TP53 mutations in The Cancer Genome Atlas of Colorectal Cancer were dispersed throughout the gene, those detected here in CRNUC cases were concentrated in the amino terminal part of the DNA-binding domain. Interestingly, the mutations in KRAS and TP53 were mutually exclusive in CRNUC, and CRNUCs with KRAS mutations had histologically serrated lesions in the gland duct. Mayo endoscopic subscore was higher in TP53-mutated CRNUCs and lower in KRAS-mutated CRNUCs. CONCLUSIONS: Our findings suggest that early-stage CRNUC can be classified into 2 groups: those developing through the carcinogenic pathway via TP53 mutations and those developing through the carcinogenic pathway via KRAS mutations.

Clinical Features and Genomic Characterization of Post-Colonoscopy Colorectal Cancer.

INTRODUCTION: Some colorectal cancers (CRCs) may be missed during colonoscopies. We aimed to determine the clinicopathological, biological, and genomic characteristics of post-colonoscopy CRCs (PCCRCs). METHODS: Of the 1,619 consecutive patients with 1,765 CRCs detected between 2008 and 2016, 63 patients with 67 PCCRCs, when colonoscopies were performed 6-60 months before diagnosis, were recruited. After excluding patients with inflammatory bowel disease, familial polyposis syndrome, CRCs that developed from diminutive adenomatous polyps, and recurrent CRCs after endoscopic resection, 32 patients with 34 PCCRCs were enrolled. The lesions' clinicopathological features, mismatch repair proteins (MMRs), and genomic alterations were investigated. RESULTS: The overall PCCRC-5y rate, rate of intramucosal (Tis) lesions, and rate of T1 or more deeply invasive cancers were 3.7% (66/1,764), 3.9% (32/820), and 3.6% (34/944), respectively. Thirty-three patients' MMRs were investigated; 7 (21%) exhibited deficient MMRs (dMMRs), comprising 4 with T2 or more deeply invasive cancers and 5 whose lesions were in the proximal colon. Twenty-three tumors' genomic mutations were investigated; PIK3CA had mutated in 5 of 6 T2 or more deeply invasive cancers, of which, 4 were located in the proximal colon. Two patients with dMMRs and BRAF mutations had poor prognoses. Sixty-one percent (17/28) of the macroscopic type 0 lesions were superficial. All superficial Tis and T1 PCCRCs were detected <24 months after the negative colonoscopies. They were distributed throughout the colon and rectum. DISCUSSION: PCCRCs may be invasive cancers in the proximal colon that exhibit dMMRs and/or PIK3CA mutations or missed early CRCs especially superficial lesions.

Clinical usefulness of the S-O clip during colorectal endoscopic submucosal dissection in difficult-to-access submucosal layer.

Background and study aims In colorectal endoscopic submucosal dissection (ESD), the S-O clip improves the accessibility to the submucosal layer of the colon. However, its safety and usefulness in difficult colorectal ESDs are unclear. Thus, in this study, we aimed to assess the effectiveness of the S-O clip in colorectal ESD in the difficult-to-access submucosal layer. Patients and methods From January 2016 to December 2016, 189 consecutive cases of colorectal ESD were performed at Hiroshima University Hospital before the S-O clip was introduced. Between January 2017 and June 2018, among 271 consecutive colorectal ESD cases, 41 cases were performed colorectal ESD using the S-O clip. We compared outcomes between the two groups (41 cases with S-O clip [use group] and 189 cases without S-O clip [non-use group]) using propensity score matching. Results Prior to propensity score matching, 41 cases with the S-O clip (use group) and 189 cases without the S-O clip (non-use group) were extracted. The degree of submucosal fibrosis was more severe and the procedure time was longer in the use group than in the non-use group. In the use and non-use groups, en bloc resection (100 % vs. 94.7 %) and complete en bloc resection (100 % vs. 92.6 %) rates were satisfactory. After propensity score matching, 33 cases in each group were extracted. As a result, complete en bloc resection rate was significantly higher in the use group than in the non-use group (100 % vs. 84.9 %). Conclusion The S-O clip is effective and can be used safely in colorectal ESD in the difficult-to-access submucosal layer.

The utility of a novel colonoscope with retroflexion for colorectal endoscopic submucosal dissection.

Background and study aims The PCF-H290TI/L produced by Olympus is a novel colonoscope equipped with some advantageous features for endoscopic treatment. It is expected to improve the potential for retroflexion and overall endoscope operability, which can reduce the difficulty of performing colorectal ESD. The aim of this study was to evaluate the utility of the novel colonoscope in colorectal ESD. Methods Three hundred and forty-eight consecutive colorectal lesions resected via ESD between June 2014 and January 2017 at Hiroshima University Hospital were included in the retroflexion ability analysis. We compared the retroflexion potential of PCF-H290TI to that of a conventional endoscope. Two hundred and twenty-seven colorectal lesions located in the left-sided colon and resected with ESD between April 2009 and February 2018 were enrolled in the treatment outcome analysis. Treatment outcomes using PCF-H290TI compared to those of the conventional colonoscope, and outcomes of the PCF-H290TI with retroflexion compared to those of the conventional colonoscope without retroflexion were evaluated by propensity score matching. Results The retroflexion rate with the PCF-H290TI was 76 %, which was significantly higher than the 44 % rate with the conventional scope. Endoscope operability was better and dissection speed was faster when using the PCF-H290TI with retroflexion compared to the conventional colonoscope without retroflexion. There were no significant differences between the groups in en bloc resection rate and adverse events. Conclusion Compared to the conventional colonoscope, the PCF-H290TI/L made it easier to perform ESD via a retrograde approach regardless of tumor location, and thus may be useful for performing colorectal ESD.

Can surveillance colonoscopy be discontinued in an elderly population with diminutive polyps?

OBJECTIVES: Surveillance colonoscopy after endoscopic resection (ER) for adenomatous polyps reduces the incidence and mortality of colorectal cancer (CRC). However, its significance in the elderly population is uncertain. The study aimed to determine whether surveillance colonoscopy should be discontinued in the elderly population. METHODS: We enrolled 105 patients who underwent baseline colonoscopy between January 2004 and December 2009 and were subsequently followed-up over 5 years in our institution. All had diminutive colorectal polyps and were aged <80 years at baseline colonoscopy and ≥80 years at follow-up in May 2018. Patients who had undergone colectomy or who had inflammatory bowel disease, familial adenomatous polyposis, Lynch syndrome, and no diminutive polyps were excluded. The cumulative incidence of the target lesion was evaluated. Histopathological diagnoses included low-grade dysplasia (LGD), high-grade dysplasia (HGD), and carcinoma. RESULTS: The target lesion was detected in 15% (16/105) of the patients. There was no invasive carcinoma; however, two HGDs were detected. There were three lesions that had increased from previously detected diminutive lesions, all of which were LGDs. There were no target lesions detected after 84 years of age, and the cumulative incidence was 0.20. The cumulative incidence was significantly higher in the group with HGD than in the group with no target lesions at baseline colonoscopy. There was no HGD after age 79 years, and the cumulative incidence was 0.019. CONCLUSION: Surveillance colonoscopy for patients with diminutive polyps may be discontinued after age 79 years.

Short-term outcomes of endoscopic submucosal dissection for superficial cecal tumors: a comparison between extension and nonextension into the appendiceal orifice.

BACKGROUND: Few studies have investigated the use of endoscopic submucosal dissection (ESD) for cecal tumors extending into the appendiceal orifice. Herein, we assessed the feasibility and safety of ESD for cecal tumors extending into the appendiceal orifice. METHODS: We retrospectively examined the outcomes of ESD for 78 patients with 78 cecal tumors (male/female ratio, 40/38; mean [standard deviation, SD] age, 67 [9] years; mean [SD] tumor size, 32 [15] mm), who underwent ESD at the Hiroshima University Hospital between October 2008 and March 2016. The indication for ESD in cecal tumors extending into the appendiceal orifice was recognition of the distal edge of the lesion in the appendix. They were classified into two groups: patients with cecal tumors extending (Group A: 29 patients, 29 tumors) and not extending (Group B: 49 patients, 49 tumors) into the appendiceal orifice. We compared the outcomes of ESD between both groups. RESULTS: No significant differences in clinicopathological characteristics were observed between both groups. The rate of severe submucosal fibrosis in Group A (48%) was significantly higher than that in Group B (24%) (p < 0.05). The mean (SD) procedure speed in Group A (14 [10] mm2/min) was significantly slower than that in Group B (23 [16] mm2/min) (p < 0.01). The en bloc resection rates in Groups A and B were 90% and 96%, respectively. There were no significant differences in adverse events reported between both groups. CONCLUSIONS: ESD for cecal tumors with extension into the appendiceal orifice is effective and safe.