Preoperative imaging evaluation of the absolute indication criteria for endoscopic submucosal dissection in early gastric cancer patients.

INTRODUCTION: Gastric cancer (GC) is a common malignant tumor with a high mortality rate. AIM: To determine the accuracy of preoperative imaging information obtained from the combined use of general gastroscopy (GS), endoscopic ultrasonography (EUS), and multi-detector computed tomography (MDCT) regarding absolute indication of endoscopic submucosal dissection (ESD) in early gastric cancer (EGC). MATERIAL AND METHODS: The relationship between clinical features of 794 EGC patients and lymph node metastasis (LNM) was analyzed. Multivariate logistic regression analysis was used to investigate the risk factors for LNM. Additionally, the accuracy of diagnosis of imaging techniques for ESD indications was determined by receiver operating characteristic (ROC) analysis. RESULTS: Data showed that tumor size > 2 cm (p = 0.0071), T1b stage (p < 0.0001), undifferentiated histology (p < 0.0001), and vascular invasion (p = 0.0007) were independent risk factors for LNM in patients with EGC. Indications for ESD have a specificity of 100% for the diagnosis of patients with LNM. Additionally, the diagnostic efficacy of the use of GS, EUS, and MDCT in identifying node positive status, T1a disease, tumor size ≤ 2 cm, and ulceration was found to be moderate with area under the curve (AUC) of receiver operating characteristic curve (ROC) of 0.71, 0.64, 0.72, and 0.68, respectively. Furthermore, the use of imaging techniques for overall indication criteria for ESD had a moderate utility value with an AUC of 0.71. CONCLUSIONS: Our data suggested that, based on the combined use of GS, EUS, and MDCT, a high specificity of patient selection for ESD treatment can be achieved.

An evaluation of the feasibility of an expanded indication of endoscopic submucosal dissection for ulcer positive early gastric cancer: a case-control study from two medical centers.

BACKGROUND: Endoscopic submucosal dissection (ESD) has increasingly gained broad application in the treatment of early gastric cancer (EGC). This study aimed at evaluating the clinical significance of lymph node metastasis (LNM) in patients with ulcer positive [UL (+)] EGC and assessing the feasibility of expanded indications of ESD for such cases. METHODS: Patients with UL (+) EGC undergoing radical surgical resection between January 2012 and December 2018 were retrospectively reviewed. Associations between clinicopathological factors and the incidence of LNM were investigated by univariate and multivariate linear regression analysis. RESULTS: Retrospective statistical analysis was performed on 653 EGC patients. The multivariate linear regression analysis showed that the presence of LNM was significantly associated with depth of invasion (P<0.0001) and lymphatic invasion (P<0.001). The proportion of EGC patients met absolute and expanded indication of ESD with positive LNM who were subject to the criteria of curative resection was 0.75% (4/532) and 6.67% (8/120), respectively. LNM between patients, which were subject to the absolute and expanded ESD indication, is significantly different (P=0.000274). CONCLUSIONS: Our study revealed that 6.67% (8/120) of EGC patients who did not meet all criteria of curative resection were present with LNM. EGC patients with UL (+), differentiated adenocarcinoma, tumor invasion pathologically diagnosed as T1a, and tumor diameter ≤3 cm showed for ESD are suggested for a carefully weighed treatment.

Expanding the indication of endoscopic submucosal dissection for undifferentiated early gastric cancer is safe or not?

BACKGROUND: Endoscopic submucosal dissection (ESD) has gained more popularity in the treatment of early gastric cancer (EGC). Although there is a lack of confirmed evidence for the feasibility of ESD for undifferentiated EGC. The aim of the study was to investigate the feasibility of ESD with expanded indications for undifferentiated EGC patients. METHODS: Data from patients with undifferentiated EGC (including signet-ring cell carcinoma, mucinous adenocarcinoma, mixed adenocarcinoma, and poorly differentiated adenocarcinoma) who underwent radical surgical resection were retrospectively reviewed. The relationship between the clinical parameters and the incidence of lymph node metastasis (LNM) was investigated. RESULTS: A total of 517 patients were included in this study. The results showed that LNM was significantly associated with ulceration, tumor size, depth of invasion, lymphatic invasion, vascular invasion, and perineural invasion. Multivariate stepwise logistic regression analysis revealed that tumor size (OR = 1.61, 95% CI = 1.03-2.52, P = 0.0367), depth of tumor invasion (OR = 2.77, 95% CI = 1.66-4.63, P = 0.0001), and lymphatic invasion (OR = 14.74, 95% CI = 1.58-137.36, P = 0.0182) were independent risk factors for LNM. In the patients who would be included under the new proposed guidelines for ESD, including men with mucosal tumors ≤2 cm and without ulceration or lymphatic or venous infiltration, LNM was present in 11.9% (14/118). CONCLUSION: Caution to be exercised in expanding application of ESD should be carefully weighed in undifferentiated EGC.

Clinicopathologic characterization and abnormal autophagy of CSF1R-related leukoencephalopathy.

BACKGROUND: CSF1R-related leukoencephalopathy, also known as hereditary diffuse leukoencephalopathy with spheroids (HDLS), is a rare white-matter encephalopathy characterized by motor and neuropsychiatric symptoms due to colony-stimulating factor 1 receptor (CSF1R) gene mutation. Few of CSF1R mutations have been functionally testified and the pathogenesis remains unknown. METHODS: In order to investigate clinical and pathological characteristics of patients with CSF1R-related leukoencephalopathy and explore the potential impact of CSF1R mutations, we analyzed clinical manifestations of 15 patients from 10 unrelated families and performed brain biopsy in 2 cases. Next generation sequencing was conducted for 10 probands to confirm the diagnosis. Sanger sequencing, segregation analysis and phenotypic reevaluation were utilized to substantiate findings. Functional examination of identified mutations was further explored. RESULTS: Clinical and neuroimaging characteristics were summarized. The average age at onset was 35.9 ± 6.4 years (range 24-46 years old). Younger age of onset was observed in female than male (34.2 vs. 39.2 years). The most common initial symptoms were speech dysfunction, cognitive decline and parkinsonian symptoms. One patient also had marked peripheral neuropathy. Brain biopsy of two cases showed typical pathological changes, including myelin loss, axonal spheroids, phosphorylated neurofilament and activated macrophages. Electron microscopy disclosed increased mitochondrial vacuolation and disorganized neurofilaments in ballooned axons. A total of 7 pathogenic variants (4 novel, 3 documented) were identified with autophosphorylation deficiency, among which c.2342C > T remained partial function of autophosphorylation. Western blotting disclosed the significantly lower level of c.2026C > T (p.R676*) than wild type. The level of microtubule associated protein 1 light chain 3-II (LC3-II), a classical marker of autophagy, was significantly lower in mutants expressed cells than wild type group by western blotting and immunofluorescence staining. CONCLUSIONS: Our findings support the loss-of-function and haploinsufficiency hypothesis in pathogenesis. Autophagy abnormality may play a role in the disease. Repairing or promoting the phosphorylation level of mutant CSF1R may shed light on therapeutic targets in the future. However, whether peripheral polyneuropathy potentially belongs to CSF1R-related spectrum deserves further study with longer follow-up and more patients enrolled. TRIAL REGISTRATION: ChiCTR, ChiCTR1800015295. Registered 21 March 2018.

Selenium pretreatment attenuates formaldehyde-induced genotoxicity in A549 cell lines.

Formaldehyde is a major industrial chemical and has been extensively used in the manufacture of synthetic resins and chemicals. Numerous studies indicate that formaldehyde can induce various genotoxic effects in vitro and in vivo. A recent study indicated that formaldehyde impaired antioxidant cellular defences and enhanced lipid peroxidation. Selenium is an important antioxidant. We hypothesized that reactive oxygen species (ROS) and lipid peroxidation are involved in formaldehyde-induced genotoxicity in human lung cancer cell line, A549 cell line. To test the hypothesis, we investigated the effects of selenium on formaldehyde-induced genotoxicity in A549 cell lines. The results indicated that exposure to formaldehyde showed the induction of DNA-protein cross-links (DPCs). Formaldehyde significantly increased the malondialdehyde levels and decreased the activities of superoxide dismutase and glutathione peroxidase. In addition, the activations of necrosis factor-κB (NF-κB) and activator protein 1 (AP-1) were induced by the formaldehyde treatment. The pretreatment with selenium counteracted the formaldehyde-induced oxidative stress, ameliorated DPCs and attenuated the activation of NF-κB and AP-1 in A549 cell lines. All the results suggested that the pretreatment with selenium attenuated the formaldehyde-induced genotoxicity through its ROS scavenging and anti-DPCs effects in A549 cell lines.

Protective effect of curcumin against formaldehyde-induced genotoxicity in A549 Cell Lines.

Formaldehyde is ubiquitous in the environment. It is known to be a genotoxic substance. We hypothesized that reactive oxygen species (ROS) and lipid peroxidation are involved in formaldehyde-induced genotoxicity in human lung cancer cell lines A549. To test this hypothesis, we investigated the effects of antioxidant on formaldehyde-induced genotoxicity in A549 Cell Lines. Formaldehyde exposure caused induction of DNA-protein cross-links (DPCs). Curcumin is an important antioxidant. Formaldehyde significantly increased malondialdehyde (MDA) levels, and decreased superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activity. In addition, the activation of NF-κB and AP-1 were induced by formaldehyde treatment. Pretreatment with curcumin counteracted formaldehyde-induced oxidative stress, ameliorated DPCs and attenuated activation of NF-κB and AP-1 in A549 Cell Lines. These results, taken together, suggest that formaldehyde induced genotoxicity through its ROS and lipid peroxidase activity and caused DPCs effects in A549 cells.

Effect of manganese on heat stress protein synthesis of new-born rats.

AIM: To study the effect of manganese (Mn) on heat stress protein 70 (HSP70) synthesis in the brain and liver of new-born rats whose mother-rats were exposed to Mn. METHODS: 32 female rats were randomly divided into four groups. One group was administrated with physiological saline only as control group, the other three groups were administrated with 7.5, 15 and 30 mg x kg(-1) manganese chloride (MnCl2) by intraperitioneal injection every two days for two weeks. After delivery, the mother-rats received MnCl2 unceasingly for a week with the same method. Then the contents of Mn Zn Cu and Fe in the livers of the new-born rats were determined by atomic absorption spectroscopy; The level of HSP70 in the brains and the livers of the new-born rats as detected by Western-dot-blotting, and the SOD activities were measured simultaneously. RESULTS: The contents of Mn in the livers of new-born rats of the experimental groups(respective 1.38+/-0.18, 2.73+/-0.65,3.44+/-0.89 microg x g(-1)) were significantly increased compared with the control group(0.88+/-0.18 microg x g(-1); P<0.01); The contents of Fe in the livers of new-born rats of 15 and 30 mg x kg(-1) experimental groups (426+/-125, 572+/-175 microg x g(-1), respectively) were significantly increased compared with the control group(286+/-42 microg x g(-1); P<0.05); the levels of Zn in the livers of the new-born rats of three experimental groups(254+/-49, 263+/-47, 213+/-28 microg x g(-1), respectively) were lower than those of the control group(335+/-50 microg x g(-1); respective P<0.05, P<0.01); and the levels of Cu showed no significant difference among the four groups(three experimental groups: 75+/-21, 68+/-241 and 78+/-18 microg x g(-1); control group: 83+/-9 microg x g(-1); P<0.05). There was a significant increase in the levels of HSP70 in the brains of new-born rats of the 30 mg x kg(-1) group (19.5 x 10(3)+/- 1.3 x 10(3)A;control group:14.3 x 10(3)+/-1.4 x 10(3)A; P<0.01) and the levels of HSP70 in the livers of new-born rats of three experimental groups(respective 19.6 x 10(3)+/- 3.9 x 10(3)A,18.5 x 10(3)+/-3.8 x 10(3)A, 22.4 x 10(3)+/-1.9 x 10(3)A) also increased than control group(13.3 x 10(3)+/-1.0 x 10(3)A;P<0.01), but the SOD activities showed no significant difference among brains of the four groups (experimental groups: 5.04+/-0.43, 4.83+/-0.48, 4.60+/-0.84 ku x g(-1); control group: 4.91+/-0.37 ku x g(-1); P<0.05). The SOD activities in the livers of 15 mg x kgP< group(5.41+/-0.44 ku x gP<) was lower than the control group(5.95+/-0.36 ku x gP<; P<0.05). CONCLUSION: While mother-rats were exposed to manganese, the metabolisms of Mn Zn and Fe of new-born rats in the livers were influenced and were situated in a stress status, thus HSP70 syntheses is induced in the brains and livers of new-born rats, but the mechanism of this effect in the developmental toxicity of Mn remains to be further studied.