Apparent diffusion coefficient and its standard deviation from diffusion-weighted imaging in preoperative predicting liver invasion by T3-staged resectable gallbladder carcinoma.

AIM: To evaluate apparent diffusion coefficient (ADC) and its standard deviation (SDADC) in preoperative predicting liver invasion by T3-staged gallbladder carcinoma (GBC). MATERIALS AND METHODS: Forty-one consecutive patients with T3-staged resectable GBC were included and divided into two sets with (n=27) and without (n=14) liver invasion. All patients underwent DWI at b-values of 0, 20, 50, 80, 100, 200, 400, 600, 800, and 1,000 s/mm2 with a 3 T magnetic resonance imaging scanner before surgery. ADC and SDADC of tumour-adjacent and tumour-distant liver tissues were measured on DWI, and were compared by Mann-Whitney U-tests. If there was a significant difference in any derived parameter, the area under the receiver operating characteristic curve (AUC) was used to assess performance of this parameter to predict liver invasion. RESULTS: DWI could differentiate between patients with and without liver invasion when b = 0, 1,000 s/mm2 (AUCs of ADC and SDADC were 0.697 and 0.714, respectively). In patients with liver invasion, mean ADC and SDADC of tumour-adjacent liver tissue were lower than of tumour-distant liver tissue when b = 0, 800 s/mm2, and = 0, 1,000 s/mm2 (all p-values <0.05). To differentiate tumour-adjacent from tumour-distant liver tissues in patients with liver invasion, AUCs of ADC were 0.687 (b = 0, 800 s/mm2) and 0.680 (b = 0, 1,000 s/mm2), and AUCs of SDADC were 0.673 (b = 0, 800 s/mm2) and 0.731 (b = 0, 1,000 s/mm2). CONCLUSIONS: DWI could have potential value in preoperative predicting liver invasion by T3-staged GBC.

Comparison of pharmacological thrombolysis with mechanical thrombectomy in thrombosed arteriovenous fistulas and grafts: a systemic review and meta-analysis.

AIM: To compare the effectiveness and safety of pharmacological thrombolysis and mechanical thrombectomy. MATERIAL AND METHODS: This review was conducted in accordance with the PRISMA guidelines. Pooled proportions and subgroup analysis were calculated for primary and secondary patency rates, technical success, clinical success, major and minor complications rates. RESULTS: This systematic review identified a total of 6,492 studies of which 17 studies were included for analysis. A total of 1,089 patients comprising 451 (41.4 %) and 638 (58.6 %) patients who underwent thrombolysis and mechanical thrombectomy procedures, respectively, were analysed. No significant differences were observed between thrombolysis and mechanical thrombectomy procedures in terms of technical success, clinical success, major and minor complications rates, primary and secondary patency rates; however, subgroup analysis of overall arteriovenous fistulas (AVFs) and arteriovenous grafts (AVGs) demonstrated a significantly higher rate of major complications within the AVF group (p=0.0248). CONCLUSION: The present meta-analysis suggests that pharmacological thrombolysis and mechanical thrombectomy procedures are similarly effective and safe; however, AVFs are subject to higher major complications compared to AVGs.

Electrolyte imbalances as poor prognostic markers in COVID-19: a systemic review and meta-analysis.

PURPOSE: Serum electrolyte imbalances are highly prevalent in COVID-19 patients. However, their associations with COVID-19 outcomes are inconsistent, and of unknown prognostic value. We aim to systematically clarify the associations and prognostic accuracy of electrolyte imbalances (sodium, calcium, potassium, magnesium, chloride and phosphate) in predicting poor COVID-19 clinical outcome. METHODS: PubMed, Embase and Cochrane Library were searched. Odds of poor clinical outcome (a composite of mortality, intensive-care unit (ICU) admission, need for respiratory support and acute respiratory distress syndrome) were pooled using mixed-effects models. The associated prognostic sensitivity, positive and negative likelihood ratios (LR + , LR-) and predictive values (PPV, NPV; assuming 25% pre-test probability), and area under the curve (AUC) were computed. RESULTS: We included 28 observational studies from 953 records with low to moderate risk-of-bias. Hyponatremia (OR = 2.08, 95% CI = 1.48-2.94, I2 = 93%, N = 8), hypernatremia (OR = 4.32, 95% CI = 3.17-5.88, I2 = 45%, N = 7) and hypocalcemia (OR = 3.31, 95% CI = 2.24-4.88, I2 = 25%, N = 6) were associated with poor COVID-19 outcome. These associations remained significant on adjustment for covariates such as demographics and comorbidities. Hypernatremia was 97% specific in predicting poor outcome (LR + 4.0, PPV = 55%, AUC = 0.80) despite no differences in CRP and IL-6 levels between hypernatremic and normonatremic patients. Hypocalcemia was 76% sensitive in predicting poor outcome (LR- 0.44, NPV = 87%, AUC = 0.71). Overall quality of evidence ranged from very low to moderate. CONCLUSION: Hyponatremia, hypernatremia and hypocalcemia are associated with poor COVID-19 clinical outcome. Hypernatremia is 97% specific for a poor outcome, and the association is independent of inflammatory marker levels. Further studies should evaluate if correcting these imbalances help improve clinical outcome.

[Clinical and pathological characteristics of immune-mediated liver injury caused by immune checkpoint inhibitors].

Objective: Cancer immunotherapy can lead to various side effects, termed immune-related adverse events (irAE). This study summarized and analyzed the clinical and pathological characteristics of immune-mediated liver injury caused by immune checkpoint inhibitors (ILICI). Methods: This is a retrospective case series study involving 11 patients diagnosed with ILICI at the Peking Union Medical College Hospital from November 2019 to November 2021. Patient demographic information and clinical data, including gender, age, ILICI onset, clinical and radiological manifestations, pathological features, treatment, and resumption of ICI were retrospectively collected and analyzed. Results: The patients were primarily males (9/11) with a median age of 65 (range: 32-73) years. ICI mainly resulted in either partial remission (4/11) or stable disease (3/11). ILICI occurred after a median of two cycles of anti-programmed cell death-1 (PD-1) therapy, with a median time from the initial and last anti-PD-1 therapy to ILICI onset of 57 days and 17 days, respectively. ILICI was mostly severe (3/11) or very severe (6/11). While the clinical and radiological manifestations were non-specific, the pathological features were active lobular hepatitis and portal inflammation, with prominent CD8+T lymphocyte infiltration. The basic treatment was hepatoprotective drugs (10/11). Glucocorticoids were used as the primary therapy (9/11) but were ineffective in 4 of 9 cases. Of these, 3 of 9 cases received combined treatment with mycophenolate mofetil (MMF), only one of whom achieved remission. By the end of the study, 2 of 11 cases had resumed ICI and neither had experienced an ILICI relapse. Conclusion: The ILICI patients in this study had a corresponding history of ICI treatment and pathological features. The main treatment included hepatoprotective drugs and glucocorticoids. Immunosuppressive drugs were added for some cases but had poor efficacy.

The clinical landscape of cell-free DNA alterations in 1671 patients with advanced biliary tract cancer.

BACKGROUND: Targeted therapies have transformed clinical management of advanced biliary tract cancer (BTC). Cell-free DNA (cfDNA) analysis is an attractive approach for cancer genomic profiling that overcomes many limitations of traditional tissue-based analysis. We examined cfDNA as a tool to inform clinical management of patients with advanced BTC and generate novel insights into BTC tumor biology. PATIENTS AND METHODS: We analyzed next-generation sequencing data of 2068 cfDNA samples from 1671 patients with advanced BTC generated with Guardant360. We carried out clinical annotation on a multi-institutional subset (n = 225) to assess intra-patient cfDNA-tumor concordance and the association of cfDNA variant allele fraction (VAF) with clinical outcomes. RESULTS: Genetic alterations were detected in cfDNA in 84% of patients, with targetable alterations detected in 44% of patients. Fibroblast growth factor receptor 2 (FGFR2) fusions, isocitrate dehydrogenase 1 (IDH1) mutations, and BRAF V600E were clonal in the majority of cases, affirming these targetable alterations as early driver events in BTC. Concordance between cfDNA and tissue for mutation detection was high for IDH1 mutations (87%) and BRAF V600E (100%), and low for FGFR2 fusions (18%). cfDNA analysis uncovered novel putative mechanisms of resistance to targeted therapies, including mutation of the cysteine residue (FGFR2 C492F) to which covalent FGFR inhibitors bind. High pre-treatment cfDNA VAF was associated with poor prognosis and shorter response to chemotherapy and targeted therapy. Finally, we report the frequency of promising targets in advanced BTC currently under investigation in other advanced solid tumors, including KRAS G12C (1.0%), KRAS G12D (5.1%), PIK3CA mutations (6.8%), and ERBB2 amplifications (4.9%). CONCLUSIONS: These findings from the largest and most comprehensive study to date of cfDNA from patients with advanced BTC highlight the utility of cfDNA analysis in current management of this disease. Characterization of oncogenic drivers and mechanisms of therapeutic resistance in this study will inform drug development efforts to reduce mortality for patients with BTC.

Deeper may not be better: relationship between catheter dysfunction and location of the catheter tip in right-sided tunnelled haemodialysis catheters.

AIM: To examine the relationship between catheter tip location and catheter dysfunction in the context of tunnelled central venous catheters (CVCs) for haemodialysis. MATERIALS AND METHODS: This was a retrospective study of 993 haemodialysis patients who underwent insertion of tunnelled CVCs of step-tip design via the right internal jugular vein (IJV). Based on intra-procedural radiographs, the catheter tip was characterised as being in the superior vena cava (SVC), cavo-atrial junction (CAJ), or deep right atrium (DRA). Patients were tracked for 90 days post-procedure for complications resulting in catheter replacement, and these were compared between cohorts. Statistical analysis was performed with Pearson's chi-square and Fisher's exact tests for categorical variables and two-sample t-test and one-way analysis of variance (ANOVA) for continuous variables. RESULTS: Ninety-five patients (9.6%) experienced catheter dysfunction necessitating replacement within 90 days of insertion. Tip location in SVC was associated with lower occurrence of catheter dysfunction (1.9%) as compared with the CAJ (8%) and DRA (11%; p=0.049). Catheter replacement due to other complications (catheter-associated bacteraemia, cuff dislodgement, exit-site infection, external catheter damage) showed no statistically significant relation to location of the CVC tip. CONCLUSION: When utilising tunnelled CVCs with a step-tip design inserted via the right IJV, location of the catheter tip in the SVC is associated with reduced occurrence of catheter dysfunction as compared to either the CAJ or DRA.

Localized Darier disease: three cases of Type 1 segmental mosaicism.

Darier disease (DD) is an autosomal dominant acantholytic dermatosis with an estimated prevalence of 1 in 30 000-100 000. A localized form of DD was first described by Kreibich in 1906 and is thought to account for 10% of all cases. A number of clinical variants have been reported including: unilateral, linear, segmental or zosteriform DD. We present a case series of three patients with localized DD.

Functional assessment of military aircrew applicants in a hypobaric chamber.

BACKGROUND: Aircrew are exposed to environmental pressure changes. In the Republic of Singapore Air Force (RSAF), applicants assessed to be at intermediate risk of otic barotrauma undergo a hypobaric chamber assessment ["trial of chamber" (TOC)] to functionally evaluate their suitability for military aircrew vocations. AIMS: To identify factors associated with TOC failure among applicants with otorhinolaryngological conditions. METHODS: All applicants to RSAF aircrew vocations who were assessed to be at intermediate risk of otic barotrauma over a 3-yr period were identified using the RSAF Aeromedical Centre's electronic database. Their medical records, as well as the TOC assessment records of the subset of applicants who underwent TOC, were reviewed for demographic data, clinical findings, and TOC outcomes. RESULTS: Of the 483 identified applicants, 374 (77%) had abnormal otoscopic findings, 103 (21%) had rhinitis symptoms, and 6 (1%) had previous ENT surgery. 123 (25%) underwent TOC, of which 20 (16%) failed. Holding other predictor variables constant, the odds of TOC failure increased by 0.79 per unit decrease in BMI (95% CI 0.63-0.99), and the odds of TOC failure increased by 0.93 per kg decrease in body weight (95% CI 0.87-1.00). An abnormal tympanogram was not a statistically significant predictor of TOC failure (OR 1.96, 95% CI 0.59-6.42). Of the 47 applicants who passed TOC and were eventually recruited, none subsequently developed otic barotrauma (mean follow-up, 3.3 yr ± 1.5 yr). CONCLUSIONS: Applicants with lower weight and BMI are more likely to develop otic barotrauma with environmental pressure change. Tympanometry cannot be reliably used to identify applicants who would more likely pass TOC.

[Diagnostic value of different serological markers and correlation analysis with disease phenotype in inflammatory bowel disease].

Objective: To explore the diagnostic value of different serological markers and the correlation with disease phenotype in inflammatory bowel disease (IBD). Methods: The clinical data of 445 IBD patients in Peking Union Medical College Hospital from June 2010 to December 2020 were retrospectively collected, including 223 cases of ulcerative colitis (UC) [111 males, 112 females, with a median age of 46(20,79) years] and 222 cases of Crohn's disease (CD) [147 males, 75 females, with a median age of 39 (19, 72) years]. The positive rates of serum anti-neutrophil cytoplasmic antibodies (ANCA), anti-Saccharomyces cerevisiae antibodies (ASCA), goblet cell autoantibodies (GAB) and pancreatic autoantibodies (PAB) in the two groups were analyzed. The sensitivity, specificity, positive predictive value and negative predictive value of UC and CD were calculated. Logistic regression was performed to analyze the relationship between different combinations of antibodies and disease phenotype. Results: The positive rates of ASCA and PAB in CD patients were 34.7% (77/222) and 38.3% (85/222), respectively, which were higher than those in UC patients [10.3% (23/223) and 4.5% (10/223), P<0.001]. The positive rate of ANCA in UC patients was 50.2% (112/223), which was higher than that in CD patients [5.4% (12/222), P<0.001]. The positive rates of serum GAB in CD and UC patients were 21.6% (48/222) and 28.3% (63/223), respectively, with no significant difference (P=0.760). In patients with CD, the sensitivity of mono-marker ASCA (+), dual-marker ASCA (+) ANCA (-), quadruple-marker ASCA (+) ANCA (-) PAB (+) GAB (-) in diagnosing CD was 34.7%, 32.9%, 20.7%, the specificity was 89.7%, 95.5%, 100.0%, the positive predictive value was 77.0%, 90.1%, 100.0%, and the negative predictive value was 58.0%, 58.7%, 55.9%, respectively. In patients with UC, the sensitivity of mono-marker ANCA (+), dual-marker ANCA (+) ASCA (-), quadruple-marker ANCA (+) ASCA (-) PAB (-) GAB (+) in diagnosing UC was 50.2%, 40.4%, 24.2%, the specificity was 94.6%, 95.5%, 100.0%, the positive predictive value was 90.3%, 90.0%, 100.0%, and the negative predictive value was 65.4%, 61.4%, 56.8%, respectively. Mono-marker ASCA (+) (OR=3.39, 95%CI: 1.59-7.21), dual-marker ASCA (+) ANCA (-) (OR=2.87, 95%CI: 1.34-6.14), triple-marker ASCA (+) ANCA (-) GAB (-) (OR=3.09, 95%CI: 1.31-7.31) and quadruple-marker ASCA (+) ANCA (-) PAB (+) GAB (-) (OR=3.15, 95%CI: 1.56-8.03) were associated with stenosis and/or penetrating type CD. The mono-marker ANCA (+) (OR=2.69, 95%CI: 1.42-5.12) and dual-marker ANCA (+) ASCA (-) (OR=2.11, 95%CI: 1.03-4.16) were associated with extensive colonic lesions in UC. Conclusion: Based on ASCA or ANCA, the combination with PAB or GAB, is conducive to IBD diagnosis, and is associated with stenosis and/or penetrating type of CD and extensive type of UC.

[Risk factors and characteristics of gut microbiota and metabolites in inflammatory bowel diseases patients with urolithiasis].

Objective: To identify the related factors and characteristics of gut microbiota and metabolites in inflammatory bowel disease (IBD) patients with urolithiasis. Methods: A total of 68 IBD patients with urolithiasis and 136 gender-and age-matched IBD patients without urolithiasis in the Department of Gastroenterology, Peking Union Medical College Hospital from January 2014 to December 2019 were recruited. The diagnosis of urolithiasis was confirmed by plain films, ultrasonography, abdominal computed tomography or intravenous urography. The clinical data of patients were collected, and the association between the clinical characteristics and urolithiasis was further analyzed. The fecal samples were collected from 10 patients with urolithiasis and 18 patients without urolithiasis, and the gut microbiota and metabolites composition were analyzed. Results: There were 49 male and 19 female IBD patients with urolithiasis, with a mean age of (36.0±12.4) years, and 98 male and 38 female patients without urolithiasis, with a mean age of (36.1±12.5) years. Univariate analysis revealed that the rate of ileostomy and the resection of small intestine in Crohn's disease (CD) patients with urolithiasis (n=34) was significantly higher than CD patients without urolithiasis (n=68) (26.5% vs 7.4%, P=0.019). And the erythrocyte sedimentation rate was also higher [26.5 (12.0, 40.8) vs 13.0 (7.2, 32.5) mm/1 h, P=0.022] in CD patients with urolithiasis. There were no significant differences in clinical characteristics and biochemical parameters between the ulcerative colitis (UC) patients with urolithiasis (n=34) and without urolithiasis (n=68) (all P>0.05). The multivariate logistic regression analysis indicated that ileostomy and the resection of small intestine were the independent related factors for urolithiasis in CD patients (OR=4.619, 95%CI: 1.178-18.111, P=0.028). There was no significant difference in α and ß diversity between the two groups (all P>0.05). At the phylum level, there was no significant difference in the abundance of microbiota (all P>0.05). At the genus level, the abundance of Enterococcus (P=0.049), Eubacterium_eligens (P=0.036) was significantly decreased. At the species level, the abundance of Bacteroides_coprocola was increased in urolithiasis group (P=0.035), while the abundance of Blautia_caecimuris was significantly decreased (P=0.042). No significant difference was found in fecal metabolites between the two groups (all P>0.05). According to LDA effect size (Lefse) analysis, taxa including Sphingomonadales, Fenollaria, Bacteroides_coprocola contributed greatly to the difference between the two groups. Conclusions: Ileostomy and the resection of small intestine are related factors for urolithiasis in patients with CD. Gut microbiota may be involved in the occurrence of urolithiasis in patients with IBD.

Combining tumor deposits with the number of lymph node metastases to improve the prognostic accuracy in stage III colon cancer: a post hoc analysis of the CALGB/SWOG 80702 phase III study (Alliance)☆.

BACKGROUND: In colon cancer, tumor deposits (TD) are considered in assigning prognosis and staging only in the absence of lymph node metastasis (i.e. stage III pN1c tumors). We aimed to evaluate the prognostic value of the presence and the number of TD in patients with stage III, node-positive colon cancer. PATIENTS AND METHODS: All participants from the CALGB/SWOG 80702 phase III trial were included in this post hoc analysis. Pathology reports were reviewed for the presence and the number of TD, lymphovascular and perineural invasion. Associations with disease-free survival (DFS) and overall survival (OS) were evaluated by multivariable Cox models adjusting for sex, treatment arm, T-stage, N-stage, lymphovascular invasion, perineural invasion and lymph node ratio. RESULTS: Overall, 2028 patients were included with 524 (26%) TD-positive and 1504 (74%) TD-negative tumors. Of the TD-positive patients, 80 (15.4%) were node negative (i.e. pN1c), 239 (46.1%) were pN1a/b (<4 positive lymph nodes) and 200 (38.5%) were pN2 (≥4 positive lymph nodes). The presence of TD was associated with poorer DFS [adjusted hazard ratio (aHR) = 1.63, 95% CI 1.33-1.98] and OS (aHR = 1.59, 95% CI 1.24-2.04). The negative effect of TD was observed for both pN1a/b and pN2 groups. Among TD-positive patients, the number of TD had a linear negative effect on DFS and OS. Combining TD and the number of lymph node metastases, 104 of 1470 (7.1%) pN1 patients were re-staged as pN2, with worse outcomes than patients confirmed as pN1 (3-year DFS rate: 65.4% versus 80.5%, P = 0.0003; 5-year OS rate: 87.9% versus 69.1%, P = <0.0001). DFS was not different between patients re-staged as pN2 and those initially staged as pN2 (3-year DFS rate: 65.4% versus 62.3%, P = 0.4895). CONCLUSION: Combining the number of TD and the number of lymph node metastases improved the prognostication accuracy of tumor-node-metastasis (TNM) staging.

Diagnostic value of the combined detection of CEA, NSE and IL-18 for lung cancer and their relationship with apoptosis gene Bcl-2.

This study aims to investigate the value of the combined detection of carcinoembryonic antigen (CEA), Neuron-specific enolase (NSE) and the level of Interleukin-18 (IL-18) in the serum in the diagnosis of lung cancer. The correlation between these parameters and the expression levels of B-cell lymphoma-2 (Bcl-2) protein were also studied. Eighty patients with lung cancer were included in the lung cancer group. These patients underwent surgery in the Department of Oncology of Huai'an Second People's Hospital between February 2016 and February 2018. During the same period, another 80 patients with benign lung lesions were registered in the benign lesion group and 80 healthy people were enrolled in the control group. Enzyme-linked immunosorbent assay (ELISA) was used to detect the expression levels of CEA, NSE and IL-18. The diagnostic critical value of these factors was used as positive indicator. When CEA, NSE and IL-18 levels were positive at the same time, the combined detection was considered to be positive. WB was used to detect Bcl-2 expression level. We also analyzed the possible correlation between CEA, NSE, IL-18 levels and the Bcl-2 expression levels. The CEA, NSE and IL-18 expression levels in the serum of the lung cancer group were significantly higher than those in the benign lesion and the control groups (p<0.05). The area under ROC curve for CEA, NSE and IL-18 respectively was 0.770 (0.697-0.843), 0.829 (0.767-0.890), 0.721 (0.642-0.800) (p<0.001). IL-18 level was negatively correlated with the level of Bcl-2 mRNA in the tissue (r=-0.380, p<0.001). In conclusion, CEA, NSE and IL-18 have a good auxiliary diagnostic value in patients with lung cancer. The combined detection could improve the sensitivity and specificity of lung can¬cer diagnosis. There was a negative correlation between IL-18 and Bcl-2 levels which suggested a potential inhibitory role of IL-18 on the lung cancer cells apoptosis pathway.

Planning and coordination of the radiological response to the coronavirus disease 2019 (COVID-19) pandemic: the Singapore experience.

Coronavirus disease 2019 (COVID-19) has spread fast and extensively around the world, with significant mortality and morbidity. As this is a respiratory infection, chest radiography and computed tomography (CT) are important imaging techniques in the work-up of this disease. Given its highly infectious nature, cross-infection within the healthcare setting and radiology departments needs to be addressed actively and prevented. We describe the response of radiology departments in Singapore to this pandemic, in terms of diagnosis, re-configuration of the department, re-organisation and segregation of staff, infection control, managerial, and leadership issues.

Silencing of TPD52 inhibits proliferation, migration, invasion but induces apoptosis of pancreatic cancer cells by deactivating Akt pathway.

Pancreatic cancer (PC) is a complex and multifactorial human malignancy with a low survival rate. Tumor protein D52 (TPD52) was abnormally expressed in several cancers and participated in tumorigenesis. However, the oncogenic effect of TPD52 on PC remains unknown. In the present study, after transfecting AsPC-1 and PANC-1 cells with NC or sh-TPD52, the CCK-8 assay, Hoechst staining, western blot, transwell assay, flow cytometry were used to examine the cell proliferation, migration, invasion and apoptosis. qRT-PCR results confirmed that the expression of TPD52 was significantly increased in PC cells, especially AsPC-1 and PANC-1 cells. The present study revealed that silencing of TPD52 significantly suppressed the proliferation, migration and invasion, but induced apoptosis of AsPC-1 and PANC-1 cells in vitro by dephosphorylating Akt at Ser473. Conversely, SC79, an Akt activator, could partially reverse the anti-metastatic effects of sh-TPD52, accompanied by the reactivating of Akt pathway. Additional in vivo studies are warranted to elucidate that knockdown of TPD52 could inhibit tumor growth in PC mice models. These findings suggested that TPD52 might be a novel therapeutic target for PC treatment.

[Pathological characteristics and survival analysis of 355 patients with gastroenteropancreatic neuroendocrine neoplasms].

Objective: Biological behavior, pathological characteristics and prognostic factors of 355 cases with gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) were analyzed in this retrospective study. Methods: In our study, 355 patients pathologically diagnosed as GEP-NENs were identified from April 2006 to November 2017 in the Fourth Hospital of Hebei Medical University. The biological behavior, pathological characteristics and prognosis were analyzed retrospectively. Results: There were 355 patients (228 males and 127 females) with a mean age of 58.3±10.7 years. GEP-NENs were detected most frequently in the stomach (48.2%), followed by the pancreas (16.1%), colorectum (14.1%), esophagus (7.6%), duodenum/jejunum(5.6%), liver (4.2%), appendix (2.3%) and gallbladder/bile duct (2.0%). The main clinical manifestations of non-functional GEP-NENs were abdominal pain (88/350, 25.14%), ventosity (77/350, 22.00%) and dysphagia (68/350, 19.43%), which were generally lacking specificity at the first diagnosis. 295 patients were treated surgically, including 45 cases of endoscopic resection and 250 cases of laparoscopic operation. Concerning to pathological grading, there were 22.5% (80/355) patients in grade 1 (G1), 12.7% (45/355) in grade 2 (G2), and 58.9% (209/355) in grade 3 (G3). The median follow-up time was 34 months. Furthermore, the 1-, 3- and 5-year overall survival calculated by Kaplan-Meier method were 80.1%, 59.8%, and 57.5%, respectively. Univariate analysis revealed that tumor site, treatment, operation type, depth of tumor invasion, TNM staging, pathological grading, vascular embolus, lymph node metastasis, tumor size, preoperative leukomonocyte level and preoperative plasma albumin were associated with overall survival (all P<0.05). Multivariate analysis showed that treatment, operation type, depth of tumor invasion, TNM staging, pathological grading, vascular embolus, lymph node metastasis and tumor size were independent prognostic factors for GEP-NENs (all P<0.05). Conclusions: The clinicopathological characteristics of GEP-NENs should be mastered by clinicians, and the standard treatment measures were also needed to be formulated based on the prognostic factors in order to improve the prognosis of patients.

[Effect and mechanism of PRDX1 in epithelial mesenchymal transformationin of gastric cancer cells].

Objective: To explore the effect and mechanism of peroxiredoxin1 (PRDX1) in epithelial mesenchymal transformation (EMT) of gastric cancer cells. Methods: The expression of PRDX1 protein was detected by immunohistochemistry (IHC) in 70 paraffin specimens of cancer and normal mucosa adjacent to gastric cancer, and the relationship between PRDX1 protein and clinicopathological characteristics was analyzed. Then PRDX1-small interfering RNA (siRNA) was synthetized and transfected into human gastric cancer cell line AGS, and 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2H tetrazolium bromide (MTT) assay was used to test cell proliferation. Transwell chamber assay was employed to test invasion of cells. Real-time quantitative polymerase chain reaction (RT-qPCR) and western blot were utilized to test the expressions of PRDX1, E-cadherin, N-cadherin, vimentin, and claudin-1. Results: The positive rate of PRDX1 protein expression in gastric cancer was 81.4%, higher than that in normal mucosa (27.1%, P<0.05). The expression of PRDX1 protein was related to invasive depth and lymph node metastasis of gastric cancer (P<0.05). The expressions of PRDX1 mRNA and protein in AGS cells (2.216±0.445, 1.212±0.136), were higher than those in GES-1 cells (0.342±0.041, 0.328±0.038) (P<0.05). When PRDX1-siRNA was transfected into AGS cells, the proliferation of AGS cells was significantly inhibited (all P<0.05). The invasion and migration rate of AGS cells in the transfection group [(112.00±17.98), (50.87±9.79)%] were significantly lower than those of the negative control group [(192.50±22.02), (83.03±8.67)%] and blank control group [(193.83±22.40), (82.40±7.21)%] (all P<0.05). The expressions of mRNA and protein of N-cadherin, vimentin and claudin-1 decreased, while the expression of E-cadherin increased when PRDX1-siRNA was transfected into AGS cells (P<0.05). Conclusion: PRDX1 may promote the development of gastric cancer by regulating the EMT of gastric cancer cells.

[Clinical characteristics and microbiome analysis in patients with anti-programmed cell death protein 1 related colitis].

Objective: To analyze clinical characteristics and monitor microbiome changes in patients with anti-PD-1 associated colitis. Methods: Two patients with non-small cell lung cancer who developed colitis after treated with anti-PD-1 antibodies were retrospectively analyzed in Peking Union Medical College Hospital from January 2019 to January 2020. The clinical symptoms, endoscopic and pathological manifestations, as well microbiome changes were analyzed and compared during pre-treatment, post-treatment and relapse. Results: The main clinical manifestations included diarrhea, elevated inflammatory indicators, colonic mucosal diffuse hyperemic edema with erosion by endoscopy. Changes in the structure of crypts were common pathological characteristics. Glucocorticoids were effective agents, which achieved clinical remission and mucosal healing. The microbiome composition of OTUs was different. After glucocorticoid treatment, the alpha diversity Observed species, Shannon, Simpson, Chao1, ACE indexes all decreased. The Firmicutes decreased with Bacteroidetes increasing in phylum level; while the Bacteroides increased with Ruminococcaceae decreasing in genus level. Lactobacillus was the potentially beneficial genus. Conclusion: Patients developing anti-PD-1 associated colitis have characteristic clinical and pathological manifestations. Glucocorticoids are effective treatment. The fecal microbiome diversity, relative abundance of major phylum and genus have changed after treatment.

[Protective effect and mechanism of Lactobacillus rhamnosus on immune checkpoint inhibitors related colitis in mice].

Objective: Modeling the immune-related adverse events (irAE) colitis in mice, and explore the protective effect and related mechanism of Lactobacillus rhamnosus GG (LGG) on irAE colitis. Methods: C57BL/6 mice were divided into dextran sodium sulfate (DSS) group (n=3), DSS+anti-programmed death receptor 1 (PD-1) group (n=4), DSS+anti-PD-1+anti-cytotoxic T lymphocyte associated protein 4 (CTLA-4) Group (n=4), DSS+anti-PD-1+anti-CTLA-4+LGG group (n=4), all were given corresponding drugs and probiotics intervention. The severity of colitis were assessed by weight loss, disease activity index (DAI), colon length, colon histopathological score. The inflammatory cytokines and T cell immunity of CD4+, CD8+, FoxP3+regulatory T cells (Treg), were detected by real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and immunohistochemical staining respectively. Results: Compared to DSS group, the Day 9 weight [(87.40±1.79)% vs (94.57±0.53)%, P<0.05], colon length [(5.33±0.27)cm vs (6.63±0.12)cm, P<0.05] were lower, and DAI score(2.66±0.24 vs 0.89±0.48), colon histopathological score (12.50±1.04 vs 5.67±0.33), tumor necrosis factor-α (TNF-α) (6.73±1.68 vs 0.91±0.40) (P<0.05), as well CD8+T cells (156.80±8.84 vs 89.00±6.66) and FoxP3+Treg cells (103.80±2.66 vs 48.33±3.18) (P<0.05) were higher in DSS+anti-PD-1+anti-CTLA-4 group. Compared to DSS+anti-PD-1+anti-CTLA-4 group, the DAI score(1.83±0.17 vs 2.66±0.24), colonic histopathology score (8.75±0.63 vs 12.50±1.04), TNF-α level (1.32±0.18 vs 6.73±1.68) (P<0.05) were lower; and CD8+T cells(97.75±3.75 vs 156.80±8.84, P<0.01) level was lower with higher FoxP3+Treg cells (126.00±8.33 vs 103.80±2.66, P=0.046) in DSS+anti-PD-1+anti-CTLA-4+LGG group. Conclusion: DSS combined with anti-PD-1 and anti-CTLA-4 can successfully modeling the irAE colitis in mice, LGG can reduce irAE colitis severity by regulating Treg cells.

[A multicenter randomized prospective study of concurrent chemoradiation with 60 Gy versus 50 Gy for inoperable esophageal squamous cell carcinoma].

Objective: To determine whether 60 Gy is superior to standard 50 Gy for definitive concurrent chemoradiation(CCRT) in esophageal squamous cell carcinoma (ESCC) using modern radiation technology in a phase Ⅲ prospective randomized trial. Methods: From April 2013 to May 2017, 331 patients from 22 hospitals who were pathologically confirmed with stage ⅢA-ⅣA ESCC were randomized to 60 Gy or 50 Gy with random number table. Total of 305 patients were analyzed, including 152 in 60 Gy group and 153 in 50 Gy group. The median age was 63 years, 242(79.3%) males and 63(20.7%) females. The median length of primary tumor was 5.6 cm. The clinical characteristics between two groups were comparable. All patients were delivered 2 Gy per fraction, 5 fractions per week. Concurrent weekly chemotherapy with docetaxel (25 mg/m(2)) and cisplatin (25 mg/m(2)) and 2 cycles consolidation chemotherapy with docetaxel (70 mg/m(2)) and cisplatin (25 mg/m(2), d1-3) were administrated. The primary endpoint was local/regional progression-free survival (LRPFS). The data were compared with Pearson chi-square test or Fisher's exact test. Results: At a median follow-up of 27.3 months, the disease progression rate was 37.5% (57/152), 43.8% (67/153) in the high and standard-dose group, respectively (χ(2)=1.251, P=0.263). The 1, 2, 3-year LRPFS rate was 75.4%, 56.8%, 52.1% and 74.2%, 58.4%, 50.1%, respectively (HR: 0.95, 95%CI: 0.69-1.31, P=0.761). The 1, 2, 3-year overall survival rate was 84.1%, 64.8%, 54.1% and 85.4%, 62.9%, 54.0%, respectively (HR: 0.98, 95%CI: 0.71-1.38, P=0.927). The 1, 2, 3-year progression-free survival rate was 70.8%, 54.2%, 48.5% and 65.5%, 51.9%, 45.1%, respectively (HR: 0.93, 95%CI: 0.68-1.26, P=0.621). The incidence rates in toxicities between the two groups were similar except for higher rate of severe pneumonitis in high dose group (χ(2)=11.596, P=0.021). Conclusions: The efficacy in disease control is similar between 60 Gy and 50 Gy using modern radiation technology concurrent with chemotherapy for ESCC. The 50 Gy should be recommended as the regular radiation dose with CCRT for ESCC.

KLF11 promotes gastric cancer invasion and migration by increasing Twist1 expression.

Gastric cancer (GC) is a leading cause of global cancer-related death. The incidence and mortality rates of gastric cancer in China are second and third ranked in all forms of malignant tumors. Krüppel-like factor11 (KLF11) is a member of the KLF family, and previous studies have shown it significantly influences epithelial ovarian, pancreatic and liver cancer proliferation, differentiation and apoptosis. However, the expression and some biological functions of KLF11 in GC are still unclear. We therefore collected and analyzed the mRNA and protein expressions of KLF11 in 59 paired gastric cancer tissues and matched healthy gastric tissue samples. We then investigated the KLF 11 biological functions and potential mechanisms in BGC823 and HGC27 gastric cancer cell lines. Analysis of KLF11 in gastric cancer specimens confirmed up-regulation compared to adjacent healthy gastric tissues, and similar results were evident in the GC cell lines. Ectopic expression of KLF11 was significantly associated with GC cell invasion and migration. KLF11 functions were most effective in Twist1 expression and knockdown, and also in KLF11 up-regulation which was accompanied by corresponding change in Twist1 expression; but these effects were inhibited when KLF11 was silenced by the small interfering RNA (siRNA). The relative Twist1 promoter region activity increased gradually with increasing KLF11 plasma, and KLF11 therefore has a critical role in regulating gastric cancer migration and invasion by increasing Twist1 expression. Finally, the results of this study should improve understanding of the KLF11 and EMT regulating network and KLF11's use as a potential therapeutic target in gastric cancer.