Objective:To investigate the role of Caspase-1/gasdermin D (GSDMD) -mediated cell pyroptosis in anti-tumor effect of cisplatin (DDP) in triple-negative breast cancer (TNBC) .Methods:HE staining and immunohistochemical staining were performed to detect the morphological changes and the expression of pyroptosis/apoptosis pathway related proteins in TNBC tissues before and after DDP-based neoadjuvant chemotherapy (NACT) . The TNBC cell line MDA-MB-231 was treated with DDP and the morphological changes were observed. The type of cell death induced by DDP was analyzed by Annexin V-FITC/PI double staining and flow cytometry. Lactate dehydrogenase (LDH) release assay and ELISA were performed to detect the release of LDH and inflammatory factors (IL-18 and IL-1β) in cell culture supernatant after DDP treatment. Western blot (WB) was performed to detect the expression of pyroptosis/apoptosis pathway related proteins in cells after DDP treatment. MDA-MB-231 cells treated with DDP were co-treated with caspase-1 specific inhibitor to inhibit pyroptois or co-treated with caspase-3 specific inhibitor to inhibit apoptosis. The effect of caspase-1 inhibitor or caspase-3 inhibitor on the anti-tumor effect of DDP was detected by MTT assay, clone formation assay, transwell assay and would healing test.Results:Reactive changes in the breast surgical specimen after DDP-based NACT included cell swelling and inflammatory cell aggregation around the tumor bed, which were more similar to pyroptosis. The up-regulation of key molecules of pyroptosis pathway post-NACT was significantly higher than that of key molecules of apoptosis pathway. Further experiments in vitro showed that DDP could induce MDA-MB-231 cells to show pyroptosis-like changes characterized by large bubbles blowing from the cellular membrane. Flow-cytometry analyses showed that the death type of MDA-MB-231 cells caused by DDP was mainly Annexin V +PI + cells (mainly lytic cells, such as pyroptosis) . Additionally, DDP treatment induced significant activation of caspase-1 and GSDMD, increased the release of LDH, IL-18 and IL-1β, however, the activation level of caspase-3, which dominates the apoptosis pathway, was significantly lower than that of caspase-1/GSDMD. Moreover, caspase-1 inhibitors (blocking the classical pyroptosis pathway) had a significantly greater inhibitory effect on the anti-tumor effect of DDP than caspase-3 inhibitors (blocking the apoptosis pathway) . Conclusion:Caspase-1/GSDMD mediated pyroptosis may play a leading role in the anti-tumor effect of DDP in triple-negative breast cancer.

Objective:To evaluate the efficacy and safety of the second session of endoscopic ultrasound-guided lauromacrogol ablation (EUS-LA) for pancreatic cystic neoplasms (PCNs).Methods:A total of 74 patients with suspected of PCNs who underwent EUS-LA in the First Medical Center of Chinese PLA General Hospital from April 2015 to December 2020 were enrolled in the study. Fifteen of them underwent the second ablation. The efficiency of EUS-LA was determined based on the change of lesion volume during the imaging follow-up, categorized into complete resolution (CR), partial resolution (PR) and stable disease (SD). The safety was determined by the complication incidence.Results:Among the 15 patients undergoing the second EUS-LA, there were 9 males and 6 females with age of 51.5±17.6 years. Thirteen patients completed imaging follow-up after the second EUS-LA, CR was achieved in 8 patients, PR in 2 patients and 3 in SD. The CR rate increased from 0 after the first ablation to 8/13 after the second ablation ( P=0.002). The median cyst diameter decreased from 22.0 mm before the second ablation to 15.0 mm after the second ablation ( Z=-2.666, P=0.008) and the median cyst volume reduced from 2 419.7 mm 3 to 1 099.5 mm 3 ( Z=-2.134, P=0.033). The complication incidence of the second ablation was 2/15, similar to that of the first ablation. Conclusion:The second ablation is effective and safe without increasing the complication incidence in patients without achieving CR after the first EUS-LA.

Objective:To compare the clinicopathological characteristics of main and accessory lesions in patients with synchronous multiple esophageal lesions (SMEL, i. e. early esophageal cancer and intraepithelial neoplasia) and to explore their correlation.Methods:Data of 80 patients with SMEL treated by endoscopic resection in The First Medical Center of Chinese PLA General Hospital from November 2006 to September 2019 were retrospectively analyzed, and the clinicopathological characteristics as well. The lesions were divided into main and accessory lesions, and their correlation in macroscopic type, lesion location, pathological type and invasion depth in 70 patients with double SMEL were investigated.Results:The age of 80 patients with SMEL was 61.3±8.32 years, more common in males (83.8%, 67/80). Fifty-seven patients (71.2%) had a history of smoking and drinking, respectively. There was a positive correlation between the size of main and accessory lesions in the 70 patients with double SMEL ( r=0.464, P<0.001). The macroscopic type ( P=0.115), location ( P=0.340) and depth of invasion ( P=0.555) of the main and accessory lesions were not correlated, but the pathological type had high correlation ( P<0.001). The consistency rate was 50.0% (35/70). Conclusion:Most SMEL patients are elderly males with a history of smoking and drinking. When one lesion is found, there is high possibility of multiple lesions. Physicians should be aware of the correlation between main and accessory lesions to avoid missed diagnosis.

Objective:To determine the safety and long-term efficacy of endoscopic ultrasonography-guided lauromacrogol ablation (EUS-LA) for treatment of pancreatic cystic neoplasms (PCNs) with a larger population.Methods:From April 2015 to April 2019, 255 patients suspected of PCNs were enrolled in the First Medical Center of Chinese PLA General Hospital in the study, and 57 patients underwent EUS-LA. The effectiveness of EUS-LA was determined based on imaging volume changes. The occurrence of complications was observed and recorded.Results:Among the 57 patients who underwent EUS-LA, 38 were female and 19 were male, with the mean age of 52.0±14.6 years. The cysts were located in the head/uncinate of the pancreas in 33 patients and in the body/tail of the pancreas in 24 patients. A total of 50 patients were followed up by imaging examinations. After treated by EUS-LA, the cyst median volume sharply reduced from 11 434.1 mm 3 to 639.4 mm 3 ( Z=-5.556, P<0.01), and the median diameter decreased from 32.0 mm to 12.0 mm ( Z=-6.161, P<0.01). Postoperative imaging showed a complete resolution in 24 patients (48.0%), partial resolution in 14 patients (28.0%), and persistent cyst in 12 patients (24.0%). The total number of ablation was 69, and there were 12 patients undergoing a second ablation. The adverse events rate was 4.3% (3/69). Among the 34 patients followed up for 12 months or more, complete resolution was observed in 18 patients (52.9%), partial resolution in 9 (26.5%), and persistent cyst in 7 (20.6%). Conclusion:EUS-LA is effective and safe for the treatment of PCNs. Its effectiveness is stable after more than 12 months′ follow-up.

Objective To evaluate the efficiency and safety of full-spectrum endoscopy for detection of major duodenal papilla. Methods Patients underwent painless gastroscopy in Chinese PLA General Hospital from March 2017 to December 2017 were enrolled and randomly divided into two groups according to random number method. The group A underwent conventional gastroscopy, and the group B underwent full-spectrum endoscopy. The detection rate of major duodenal papilla was calculated and compared between the two groups. Results A total of 100 patients were recruited in the study, including 51 in the group A and 49 in the group B. The whole detection rate of major duodenal papilla of the group B was higher than that of the group A [79. 59％ (39/49) VS 41. 18％ (21/51), χ2 =15. 366, P=0. 000]. There was no statistical difference on the whole plus partial detection rate of major duodenal papilla between the two groups [100. 00％ (49/49) VS 92. 16％ (47/51), χ2=2. 221, P=0. 136]. All patients completed endoscopy examination succesfully without bleeding, peforation or death. Conclusion With the broad view-field, full-spectrum endoscopy is useful to improve the efficiency and safety in detection of major duodenal papilla.

Objective To investigate the recurrence and risk factors of gastric high-grade intraepithelial neoplasia(HGIN)and early gastric cancer(EGC)after endoscopic submucosal dissection (ESD). Methods The clinical and follow-up data on 444 patients(451 lesion)with HGIN and EGC undergoing ESD in Digestive Endoscopy Center of Chinese PLA General Hospital from November 2006 to January 2016 were summarized, and the risk factors of recurrence were analyzed. Results A total of 410 patients were followed-up, and the recurrence rate was 3.2%(13 patients, 13 lesions), with mean recurrence time of 17.6±9.6 months(6-38 months). Univariate and multivariate analysis revealed that the size of the lesion>4.0 cm was the only risk factor of recurrence(P=0.012,OR=10.855,95%CI:1.673~70.442). Conclusion The rate of recurrence is increasing with the EGC extending, therefore, postoperative monitoring should be strengthened to patients with larger lesion.

Objective To evaluate the diagnostic efficiency of full-spectrum endoscopy(FUSE) versus conventional colonoscopy for colonic polyps and adenoma. Methods Patients who underwent colonoscopy were randomly allotted into two groups according to randomization and self-control criteria. Patients in group A underwent conventional endoscopy firstly and then to FUSE. Patients in group B were opposite performed the examinations. The polyps and adenomatous polyps were resected or biopsied for pathological examination. Miss rate of colonic polyps as well as adenomatous polyps was calculated. Results A total of 100 patients were recruited for the study,including 45 in group A and 55 in group B. FUSE was significantly superior compared to conventional endoscopy with lower miss rate of polyps(6.52% VS 34.04%,χ2=17.685,P=0.000)as well as adenomatous polyps(5.00% VS 34.38%, χ2=11.774, P=0.001). For the first endoscopic examination,the adenomatous polyps which were found out by FUSE were more than that of ordinary colonoscopy in the right colon(χ2=5.153,P=0.023). The size of adenoma found by ordinary colonoscopy and FUSE was no statistically different whether in the first(t=0.334,P=0.739)or second(t=1.297,P=0.219)endoscopic examinations. Conclusion FUSE is useful to improve the quality of endoscopic examination because of its broad view-field.

OBJECTIVETo compare the safety and efficiency of endoscopic submucosal tunnel dissection (ESTD) and endoscopic submucosal dissection (ESD) for large esophageal superficial neoplasms.

METHODSA total of 235 consecutive patients undergoing endoscopic resection for esophageal neoplasms between October, 2010 and June, 2013 in our endoscopy center were analyzed retrospectively. According to the inclusion and exclusion criteria, 29 patients receiving ESTD or ESD for large esophageal superficial neoplasms were enrolled for data analysis.

RESULTSOf the 29 patients, 11 underwent ESTD and 18 received ESD. The dissection speed of ESTD was significantly higher than that of ESD (22.4∓5.2 mm(2)/min vs 12.2∓4.0 mm(2)/min, P<0.05). Despite a similar en bloc rate between the two groups (100% [11/11] vs 88.9% [16/18], P>0.05), the radical curative rate of ESTD was significantly greater than that of ESD (81.8% [9/11] vs 66.7% [12/18], P<0.05). No serious bleeding or perforation occurred in the patients except for 1 in ESD group with intraoperative bleeding, which was managed with hemostatic forceps. Eight patients had postoperative esophageal strictures in relation with circumferential extension and the longitudinal length (P<0.05).

CONCLUSIONESTD is a safe and effective alternative for large esophageal superficial neoplasms with a shortened operative time, a higher dissection speed and a higher radical curative rate in comparison with ESD, but postoperative esophageal strictures should be closely monitored especially for lesions more than 3/4 of the circumferential extension or exceeding 50 mm.

Aged ; Endoscopy ; Esophageal Neoplasms ; surgery ; Esophagus ; surgery ; Female ; Humans ; Male ; Middle Aged ; Mucous Membrane ; surgery ; Retrospective Studies

Objective To compare the safety and efficiency of endoscopic submucosal tunnel dissection (ESTD) and endoscopic submucosal dissection (ESD) for large esophageal superficial neoplasms. Methods A total of 235 consecutive patients undergoing endoscopic resection for esophageal neoplasms between October, 2010 and June, 2013 in our endoscopy center were analyzed retrospectively. According to the inclusion and exclusion criteria, 29 patients receiving ESTD or ESD for large esophageal superficial neoplasms were enrolled for data analysis. Results Of the 29 patients, 11 underwent ESTD and 18 received ESD. The dissection speed of ESTD was significantly higher than that of ESD (22.4±5.2 mm2/min vs 12.2±4.0 mm2/min, P<0.05). Despite a similar en bloc rate between the two groups (100%[11/11]vs 88.9%[16/18], P>0.05), the radical curative rate of ESTD was significantly greater than that of ESD (81.8%[9/11]vs 66.7%[12/18], P<0.05). No serious bleeding or perforation occurred in the patients except for 1 in ESD group with intraoperative bleeding, which was managed with hemostatic forceps. Eight patients had postoperative esophageal strictures in relation with circumferential extension and the longitudinal length (P<0.05). Conclusions ESTD is a safe and effective alternative for large esophageal superficial neoplasms with a shortened operative time, a higher dissection speed and a higher radical curative rate in comparison with ESD, but postoperative esophageal strictures should be closely monitored especially for lesions more than 3/4 of the circumferential extension or exceeding 50 mm.

Objective To compare the safety and efficiency of endoscopic submucosal tunnel dissection (ESTD) and endoscopic submucosal dissection (ESD) for large esophageal superficial neoplasms. Methods A total of 235 consecutive patients undergoing endoscopic resection for esophageal neoplasms between October, 2010 and June, 2013 in our endoscopy center were analyzed retrospectively. According to the inclusion and exclusion criteria, 29 patients receiving ESTD or ESD for large esophageal superficial neoplasms were enrolled for data analysis. Results Of the 29 patients, 11 underwent ESTD and 18 received ESD. The dissection speed of ESTD was significantly higher than that of ESD (22.4±5.2 mm2/min vs 12.2±4.0 mm2/min, P<0.05). Despite a similar en bloc rate between the two groups (100%[11/11]vs 88.9%[16/18], P>0.05), the radical curative rate of ESTD was significantly greater than that of ESD (81.8%[9/11]vs 66.7%[12/18], P<0.05). No serious bleeding or perforation occurred in the patients except for 1 in ESD group with intraoperative bleeding, which was managed with hemostatic forceps. Eight patients had postoperative esophageal strictures in relation with circumferential extension and the longitudinal length (P<0.05). Conclusions ESTD is a safe and effective alternative for large esophageal superficial neoplasms with a shortened operative time, a higher dissection speed and a higher radical curative rate in comparison with ESD, but postoperative esophageal strictures should be closely monitored especially for lesions more than 3/4 of the circumferential extension or exceeding 50 mm.