Magnifying Colonoscopy Findings for Differential Diagnosis of Sessile Serrated Adenoma/Polyps and Hyperplastic Polyps

Sessile serrated adenoma/polyps (SSA/Ps) are thought to be precursors of colorectal cancers. However, current endoscopic techniques for differentiating SSA/Ps from conventional hyperplastic polyps (HPs) have low diagnostic accuracy. The aim of the present study was to assess the ability of mucosal crypt patterns to distinguish SSA/Ps from HPs. We examined 140 lesions from 93 patients that had been diagnosed histologically as SSA/Ps or HPs at the Showa University Hospital between June 2010 and May 2012. Three experienced colonoscopists reviewed the endoscopic findings of magnifying colonoscopy. Type II open-shape (Type II-O) pit patterns and varicose microvascular vessels (VMVs) were identified according to previously proposed definitions. Although 140 lesions were initially identified for the study, 27 lesions were excluded from analysis because of insufficient endoscopic findings. Thus, endoscopic findings from a total of 113 lesions (68 SSA/Ps and 45 HPs) were evaluated. Of 113 serrated polyps, 51 lesions (44 SSA/Ps and 7 HPs; P<0.01) had Type II-O pit patterns. The inter- and intra-observer agreement for these patterns among three colonoscopists was κ=0.61 (range 0.57–0.65) and κ=0.68 (range 0.52–0.94), respectively. The positive predictive value (PPV), negative predictive value (NPV), sensitivity, and specificity of Type II-O pit patterns for differentiating between SSA/P and HP were 86%, 61%, 65%, and 84%, respectively. In contrast, the PPV, NPV, sensitivity, and specificity of VMVs were 68%, 43%, 37%, and 73%, respectively. The results indicate that Type II-O mucosal crypt patterns may be useful for the differential diagnosis of SSAPs and HPs

Smoking enhances the expression of angiotensin-converting enzyme 2 involved in the efficiency of severe acute respiratory syndrome coronavirus 2 infection

Smoking is one of the risk factors most closely related to the severity of coronavirus disease 2019 (COVID-19). However, the relationship between smoking history and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infectivity is unknown. In this study, we evaluated the ACE2 expression level in the lungs of current smokers, ex-smokers, and nonsmokers. The ACE2 expression level of ex-smokers who smoked cigarettes until recently (cessation period shorter than 6 months) was higher than that of nonsmokers and ex-smokers with a long history of nonsmoking (cessation period longer than 6 months). We also showed that the efficiency of SARS-CoV-2 infection was enhanced in a manner dependent on the angiotensin-converting enzyme 2 (ACE2) expression level. Using RNA-seq analysis on the lungs of smokers, we identified that the expression of inflammatory signaling genes was correlated with ACE2 expression. Notably, with increasing duration of smoking cessation among ex-smokers, not only ACE2 expression level but also the expression levels of inflammatory signaling genes decreased. These results indicated that smoking enhances the expression levels of ACE2 and inflammatory signaling genes. Our data suggest that the efficiency of SARS-CoV-2 infection is enhanced by smoking-mediated upregulation of ACE2 expression level

Clinicopathological and Molecular Features of Laterally Spreading Tumors

Colorectal flat-elevated neoplasms can be classified into small-flat adenoma and laterally spreading tumors (LSTs), which can then be sub-categorized into granular-type (LST-G) and nongranular-type (LST-NG) LSTs with possible biological differences between them. We evaluated clinicopathological features and KRAS / BRAF mutations in 24 LST-Gs and 57 LST-NGs. PCR-based pyrosequencing assays were used to determine the presence of activating mutations in codons 12 and 13 of KRAS and in codon 600 of BRAF. Significant differences between LST-Gs and LST-NGs were observed in tumor size (30mm vs. 15mm, P<0.0001) and the frequency of KRAS mutations (75%, 18/24 vs. 5%, 3/57, P< 0.0001). For LST-NGs, the histological grade was increased with an increase in the tumor size. The frequency of submucosal cancer (SM-ca) was also higher in tumors of at least 20mm than in tumors smaller than 20mm (P<0.05). In contrast, there was no indication of a size-dependent increase in the histological grade. No significant difference in the frequency of KRAS mutation in LST-Gs and LST-NGs was related to tumor size. Two subtypes of LSTs were observed to have different clinicopathological and molecular characteristics. These findings suggest that different molecular mechanisms could exist in these subtypes of colorectal flat-type neoplasms

Accuracy of the Differential Diagnosis of Colorectal Serrated Polyps Using a Conventional Endoscope: A Prospective Study

Some serrated polyps （SPs） are thought to be precursors of colorectal cancers. However, the endoscopic diagnosis of sessile serrated adenoma/polyps （SSA/Ps） has been reported to have a low accuracy. The aim of this study was to clarify the ability to distinguish between SSA/Ps and non-SSA/Ps by using mucosal crypt patterns combined with endoscopic findings. In total, 457 consecutive patients who underwent endoscopic resection for colorectal polyps at the Showa University Hospital from April 2007 to December 2010 were prospectively enrolled in this study. Before treatment, mucosal crypt patterns of the lesions were classified into three types （hyperplastic, adenomatous, and mixed pattern）. When the lesion had an adenomatous pattern with a cerebriform appearance or mixed pattern, it was diagnosed as a traditional serrated adenoma （TSA）. If the lesion had a hyperplastic pattern and was sized 6mm or more in the proximal colon or 10mm or more in the distal colon, it was diagnosed as an SSA/P by the endoscopist. We analyzed 1,151 colorectal polyps in this study. Endoscopically, 117 polyps were diagnosed as SSA/Ps or hyperplastic polyps （HPs）, 998 polyps were conventional adenomas, and 36 polyps were TSAs, with diagnostic accuracies of 94.7％, 94.1％, and 97.3％, respectively. Of the 117 polyps diagnosed as SSA/Ps or HPs, 59 lesions met our criteria for SSA/Ps, with a diagnostic accuracy of 70.9％. Our results indicate that the combination of mucosal crypt patterns and endoscopic findings may be useful for differentiating between SPs and non-SPs. However, additional specific endoscopic features of SSA/Ps are still needed

Distinct Molecular Features of Different Macroscopic Subtypes of Colorectal Neoplasms

<div><p>Background</p><p>Colorectal adenoma develops into cancer with the accumulation of genetic and epigenetic changes. We studied the underlying molecular and clinicopathological features to better understand the heterogeneity of colorectal neoplasms (CRNs).</p><p>Methods</p><p>We evaluated both genetic (mutations of <i>KRAS</i>, <i>BRAF</i>, <i>TP53</i>, and <i>PIK3CA</i>, and microsatellite instability [MSI]) and epigenetic (methylation status of nine genes or sequences, including the CpG island methylator phenotype [CIMP] markers) alterations in 158 CRNs including 56 polypoid neoplasms (PNs), 25 granular type laterally spreading tumors (LST-Gs), 48 non-granular type LSTs (LST-NGs), 19 depressed neoplasms (DNs) and 10 small flat-elevated neoplasms (S-FNs) on the basis of macroscopic appearance.</p><p>Results</p><p>S-FNs showed few molecular changes except <i>SFRP1</i> methylation. Significant differences in the frequency of <i>KRAS</i> mutations were observed among subtypes (68% for LST-Gs, 36% for PNs, 16% for DNs and 6% for LST-NGs) (P<0.001). By contrast, the frequency of <i>TP53</i> mutation was higher in DNs than PNs or LST-Gs (32% vs. 5% or 0%, respectively) (P<0.007). We also observed significant differences in the frequency of CIMP between LST-Gs and LST-NGs or PNs (32% vs. 6% or 5%, respectively) (P<0.005). Moreover, the methylation level of LINE-1 was significantly lower in DNs or LST-Gs than in PNs (58.3% or 60.5% vs. 63.2%, P<0.05). <i>PIK3CA</i> mutations were detected only in LSTs. Finally, multivariate analyses showed that macroscopic morphologies were significantly associated with an increased risk of molecular changes (PN or LST-G for <i>KRAS</i> mutation, odds ratio [OR] 9.11; LST-NG or DN for <i>TP53</i> mutation, OR 5.30; LST-G for <i>PIK3CA</i> mutation, OR 26.53; LST-G or DN for LINE-1 hypomethylation, OR 3.41).</p><p>Conclusion</p><p>We demonstrated that CRNs could be classified into five macroscopic subtypes according to clinicopathological and molecular differences, suggesting that different mechanisms are involved in the pathogenesis of colorectal tumorigenesis.</p></div

Clinicopathological features of colorectal neoplasms.

<p>*, all cases were submucosal cancers. Proximal, cecum, ascending and transverse colon; distal, descending and sigmoid colon, and rectum; LGD, low grade dysplasia; HGD, high grade dysplasia; PN, polypoid neoplasm; LST-G, granular type laterally spreading tumor; LST-NG, non-granular type LST; S-FN, small flat-elevated neoplasm; DN, depressed neoplasm; NA, not applicable.</p