In the last years,an increasing interest has been raised on non-polypoid colorectal tumors(NPT) and in particular on large flat neoplastic lesions beyond 10 mm tending to grow laterally,called laterally spreading tumo...In the last years,an increasing interest has been raised on non-polypoid colorectal tumors(NPT) and in particular on large flat neoplastic lesions beyond 10 mm tending to grow laterally,called laterally spreading tumors(LST).LSTs and large sessile polyps have a greater frequency of high-grade dysplasia and local invasiveness as compared to pedunculated lesions of the same size and usually represent a technical challenge for the endoscopist in terms of either diagnosis and resection.According to the Paris classification,NPTs are distinguished in slightly elevated(0-Ⅱa,less than 2.5 mm),flat(0-Ⅱb) or slightly depressed(0-Ⅱc).NPTs are usually flat or slightly elevated and tend to spread laterally while in case of depressed lesions,cell proliferation growth progresses in depth in the colonic wall,thus leading to an increased risk of submucosal invasion(SMI) even for smaller neoplasms.NPTs may be frequently missed by inexperienced endoscopists,thus a careful training and precise assessment of all suspected mucosal areas should be performed.Chromoendoscopy or,if possible,narrow-band imaging technique should be considered for the estimation of SMI risk of NPTs,and the characterization of pit pattern and vascular pattern may be useful to predict the risk of SMI and,therefore,to guide the therapeutic decision.Lesions suitable to endoscopic resection are those confined to the mucosa(or superficial layer of submucosa in selected cases) whereas deeper invasion makes endoscopic therapy infeasible.Endoscopic mucosal resection(EMR,piecemeal for LSTs > 20 mm,en bloc for smaller neoplasms) remains the first-line therapy for NPTs,whereas endoscopic submucosal dissection in high-volume centers or surgery should be considered for large LSTs for which en bloc resection is mandatory and cannot be achieved by means of EMR.After piecemeal EMR,follow-up colonoscopy should be performed at 3 mo to assess resection completeness.In case of en bloc resection,surveillance colonoscopy should be scheduled at 3 years for adenomatous lesions ≥ 1 cm,or in presence of villous features or high-grade dysplasia patients(regardless of the size),while less intensive surveillance(colonoscopy at 5-10 years) is needed in case of single(or two) NPT < 1 cm presenting tubular features or low-grade dysplasia at histology.展开更多
AIM： To investigate the histopathological and geneticdifferences between polypoid growth （PG） and nonpolypoid growth （NPG） submucosal invasive colorectal carcinoma （CRC）.METHODS： A total of 96 cases of submuco...AIM： To investigate the histopathological and geneticdifferences between polypoid growth （PG） and nonpolypoid growth （NPG） submucosal invasive colorectal carcinoma （CRC）.METHODS： A total of 96 cases of submucosal CRC were divided into two groups according to their growth type;60 cases of PG and 36 cases of NPG. The size, histological degree of dysplasia, depth of submucosal invasion and lymph node metastasis were compared between the two groups. Furthermore, expression of p53 was detected by immunohistochemical staining, and K-ras gene mutation was examined by polymerase chain reaction based single-strand conformation polymorphism （SSCP）.RESULTS： The average size of the lesions in the NPG group was significantly smaller than those in the PG group （7.5 mm vs 13.8 mm, P 〈 0.001）. The histological degree of dysplasia tended to be more severe in NPG group, while the incidence of submucosal massive invasion and the lymph node metastasis were both significantly higher in the NPG type than in the PG group （64.3% vs 43.3%, P = 0.004; 43% vs 7%, P =0.008, respectively）. In addition, K-ras gene mutations were detected in 67% of lesions in the PG group, but none in the NPG group, while no difference in p53immunohistochemical expression was found between the two groups.CONCLUSION： Compared with PG submucosal CRC,NPG type demonstrates more frequent submucosal massive invasion, more lymph node metastasis and a higher degree dysplasia. Genetically, NPG type shows much less frequent K-ras mutation.展开更多
AIM To comparatively investigate the cellular and molecular characteristics of low-grade slightly elevated adenomas and polypoid adenomas.METHODS Colorectal tumors were collected from 24 patients with slightly elevate...AIM To comparatively investigate the cellular and molecular characteristics of low-grade slightly elevated adenomas and polypoid adenomas.METHODS Colorectal tumors were collected from 24 patients with slightly elevated adenomas and 23 patients with polypoid adenomas. five commonly mutated genes(APC, BRAf, KRAS, NRAS, and PIK3CA) were selected for mutational analysis. Paraffin-embedded tumor sections were used to calculate the apoptotic index(AI) and Ki-67 labeling index(KLI). Two pure colorectal epithelial cell lines were created by pooling the slightly elevated and polypoid tumors. western blots, luciferase assays for β-catenin-T-cell factor protein/β-cateninlymphoid enhancer factor(β-catenin-TCf/LEf)-driven transcriptional activity, and caspase activity assays were conducted on the two cell lines.RESULTS Slightly elevated lesions showed a significantly lower APC mutational frequency and a significantly higher KRAS mutational frequency(both P < 0.05). Slightly elevated lesions showed a significantly lower AI(P < 0.05). β-catenin and β-catenin-TCf/LEf-driven transcriptional activity was significantly upregulated in slightly elevated lesions(both P < 0.05). In slightly elevated lesions, c-Myc was significantly downregulated, while cyclin D1 was significantly upregulated(both P < 0.05). β-catenin-TCf/LEf-driven transcriptional activity was negatively correlated with c-Myc(ρ =-0.78). Slightly elevated lesions displayed significant Bcl-2 and Bcl-x L upregulation(both P < 0.05) along with significant decreases in caspase-9 and caspase-3 activity(both P < 0.05). c-Myc was negatively correlated with Bcl-2 and Bcl-x L(ρ =-0.74 and-0.78, respectively).CONCLUSION The lower apoptotic activity of low-grade slightly elevated adenomas can be partly attributed to upregulated β-catenin pathway activity and downregulated c-Myc expression.展开更多
文摘In the last years,an increasing interest has been raised on non-polypoid colorectal tumors(NPT) and in particular on large flat neoplastic lesions beyond 10 mm tending to grow laterally,called laterally spreading tumors(LST).LSTs and large sessile polyps have a greater frequency of high-grade dysplasia and local invasiveness as compared to pedunculated lesions of the same size and usually represent a technical challenge for the endoscopist in terms of either diagnosis and resection.According to the Paris classification,NPTs are distinguished in slightly elevated(0-Ⅱa,less than 2.5 mm),flat(0-Ⅱb) or slightly depressed(0-Ⅱc).NPTs are usually flat or slightly elevated and tend to spread laterally while in case of depressed lesions,cell proliferation growth progresses in depth in the colonic wall,thus leading to an increased risk of submucosal invasion(SMI) even for smaller neoplasms.NPTs may be frequently missed by inexperienced endoscopists,thus a careful training and precise assessment of all suspected mucosal areas should be performed.Chromoendoscopy or,if possible,narrow-band imaging technique should be considered for the estimation of SMI risk of NPTs,and the characterization of pit pattern and vascular pattern may be useful to predict the risk of SMI and,therefore,to guide the therapeutic decision.Lesions suitable to endoscopic resection are those confined to the mucosa(or superficial layer of submucosa in selected cases) whereas deeper invasion makes endoscopic therapy infeasible.Endoscopic mucosal resection(EMR,piecemeal for LSTs > 20 mm,en bloc for smaller neoplasms) remains the first-line therapy for NPTs,whereas endoscopic submucosal dissection in high-volume centers or surgery should be considered for large LSTs for which en bloc resection is mandatory and cannot be achieved by means of EMR.After piecemeal EMR,follow-up colonoscopy should be performed at 3 mo to assess resection completeness.In case of en bloc resection,surveillance colonoscopy should be scheduled at 3 years for adenomatous lesions ≥ 1 cm,or in presence of villous features or high-grade dysplasia patients(regardless of the size),while less intensive surveillance(colonoscopy at 5-10 years) is needed in case of single(or two) NPT < 1 cm presenting tubular features or low-grade dysplasia at histology.
文摘AIM： To investigate the histopathological and geneticdifferences between polypoid growth （PG） and nonpolypoid growth （NPG） submucosal invasive colorectal carcinoma （CRC）.METHODS： A total of 96 cases of submucosal CRC were divided into two groups according to their growth type;60 cases of PG and 36 cases of NPG. The size, histological degree of dysplasia, depth of submucosal invasion and lymph node metastasis were compared between the two groups. Furthermore, expression of p53 was detected by immunohistochemical staining, and K-ras gene mutation was examined by polymerase chain reaction based single-strand conformation polymorphism （SSCP）.RESULTS： The average size of the lesions in the NPG group was significantly smaller than those in the PG group （7.5 mm vs 13.8 mm, P 〈 0.001）. The histological degree of dysplasia tended to be more severe in NPG group, while the incidence of submucosal massive invasion and the lymph node metastasis were both significantly higher in the NPG type than in the PG group （64.3% vs 43.3%, P = 0.004; 43% vs 7%, P =0.008, respectively）. In addition, K-ras gene mutations were detected in 67% of lesions in the PG group, but none in the NPG group, while no difference in p53immunohistochemical expression was found between the two groups.CONCLUSION： Compared with PG submucosal CRC,NPG type demonstrates more frequent submucosal massive invasion, more lymph node metastasis and a higher degree dysplasia. Genetically, NPG type shows much less frequent K-ras mutation.
基金Supported by the Yongchuan Chongqing Medical University Hospital Fund,no.YJYB2012009
文摘AIM To comparatively investigate the cellular and molecular characteristics of low-grade slightly elevated adenomas and polypoid adenomas.METHODS Colorectal tumors were collected from 24 patients with slightly elevated adenomas and 23 patients with polypoid adenomas. five commonly mutated genes(APC, BRAf, KRAS, NRAS, and PIK3CA) were selected for mutational analysis. Paraffin-embedded tumor sections were used to calculate the apoptotic index(AI) and Ki-67 labeling index(KLI). Two pure colorectal epithelial cell lines were created by pooling the slightly elevated and polypoid tumors. western blots, luciferase assays for β-catenin-T-cell factor protein/β-cateninlymphoid enhancer factor(β-catenin-TCf/LEf)-driven transcriptional activity, and caspase activity assays were conducted on the two cell lines.RESULTS Slightly elevated lesions showed a significantly lower APC mutational frequency and a significantly higher KRAS mutational frequency(both P < 0.05). Slightly elevated lesions showed a significantly lower AI(P < 0.05). β-catenin and β-catenin-TCf/LEf-driven transcriptional activity was significantly upregulated in slightly elevated lesions(both P < 0.05). In slightly elevated lesions, c-Myc was significantly downregulated, while cyclin D1 was significantly upregulated(both P < 0.05). β-catenin-TCf/LEf-driven transcriptional activity was negatively correlated with c-Myc(ρ =-0.78). Slightly elevated lesions displayed significant Bcl-2 and Bcl-x L upregulation(both P < 0.05) along with significant decreases in caspase-9 and caspase-3 activity(both P < 0.05). c-Myc was negatively correlated with Bcl-2 and Bcl-x L(ρ =-0.74 and-0.78, respectively).CONCLUSION The lower apoptotic activity of low-grade slightly elevated adenomas can be partly attributed to upregulated β-catenin pathway activity and downregulated c-Myc expression.
