[Key updates and interpretation of the ninth version of AJCC staging system for neuroendocrine tumors of the stomach].

The cancer staging system of the American Joint Committee on Cancer (AJCC) is the most widely used clinical basis for tumor staging. In October 2023, AJCC released the staging system (ninth version) for the neuroendocrine tumors of stomach (NET), which has been implemented in January 2024. The ninth version of NET staging system mainly updated the histopathologic classification, diagnosis and staging methods, clinical and pathological staging, prognosis grade, tumor and non-tumor prognostic features. The update and implementation of the staging system provide a more detailed reference for the accurate diagnosis, staging and precise treatment of gastric neuroendocrine tumors. Moreover, it is convenient for clinicians to carry out clinical practice. The purpose of our article is to provide a high-level overview of the major changes in AJCC staging system (version 9) for gastric NET based on the latest evidence-based medical research.

[Robotic hilar cholangiocarcinoma radical resection compared with laparotomy in prognosis].

Objective: To compare the long term and short term outcomes between robotic and open surgery for hilar cholangiocarcinoma radical resection. Methods: This is a single-center and retrospective case-control study. Patients underwent hilar cholangiocarcinoma radical resection between January 2016 and December 2016 at Department of Hepatobiliary Surgery of the General Hospital of the Chinese People's Liberation Army were included. Safety, effectiveness and long-term prognosis of tumors were evaluated. Patients were divided into robotic hilar cholangiocarcinoma radical surgery group (robotic group, n=16) and open hepatic hilar cholangiocarcinoma radical surgery group (open group, n=31) . All cases were confirmed by pathology histological. Age, gender, histology, resection margin status, extent of surgical resection, disease-free survival (DFS) , and overall survival (OS) were retrospectively collected and analyzed.In the follow-up cohort, the primary outcome was patient death and the secondary outcome was tumor recurrence. Continuous variables were expressed as means and medians and were compared using the Student t test if normally distributed or Wilcoxon-Mann-Whitney test for nonparametric variables. Discrete variables were expressed as frequency and percentages and χ(2) or Fisher exact test, when appropriate, were used for comparisons. Kaplan-Meier curves were used to calculate the probability of survival and comparisons were performed using log-rank test. Results: In this study, compared with the open group, the robotic group had a longer operation time ( (338±71) minutes vs. (256±56) minutes, t=4.251, P=0.001) , but the intraoperative blood loss was less (100 ml vs. 200 ml, Z=121.50, P=0.040) , the gastric tube removal time was earlier (3 days vs. 4 days, Z=136.0, P=0.011) , and the postoperative hospital stay was shorter (9 days vs. 12 days, Z=144.50, P=0.040) , and the difference was statistically significant.There was no significant difference in the blood transfusion rate, R0 resection rate, and tumor size between the two groups.The recurrence rates in the robotic group and open surgery were 53.3% and 67.0%, respectively (χ(2)=1.04, P=0.307) .The median survival time of the robotic group and the open group was 22.0 months and 25.0 months. There was no significant difference in the overall survival rate between the two groups (P>0.05) . Conclusion: Compared with laparotomy, robotic HCC radical resection could have an equivalence or non-inferiority approach with acceptable long-term outcome.

[Postoperative complications and survival analysis of 1 118 cases of open splenectomy and azygoportal disconnection in the treatment of portal hypertension].

Objective: To analyze the recent postoperative and long-term postoperative complications of open-splenectomy and disconnection in patients with portal hypertension. Methods: There were 1 118 cases with portal hypertension who underwent open splenectomy and azygoportal disconnection from April 2010 to September 2015 at Department of Surgery, People's Liberation Army 302 Hospital. Retrospective case investigation and telephone follow-up were conducted in October 2016. All patients had history of upper gastrointestinal bleeding before operation. Short-term complications after surgery were recorded including secondary laparotomy of postoperative abdominal hemostasis, severe infection, intake disorders, liver insufficiency, postoperative portal vein thrombosis and perioperative mortality. Long-term data including postoperative upper gastrointestinal rebleeding, postoperative survival rate and incidence of postoperative malignancy were recorded, too. GraphPad Prism 5 software for data survival analysis and charting. Results: Postoperative short-term complications in 1 118 patients included secondary laparotomy of postoperative abdominal hemostasis(1.8%, 21/1 118), severe infection(2.9%, 32/1 118), intake disorders(1.0%, 11/1 118), liver dysfunction (1.6%, 18/1 118), postoperative portal vein thrombosis(47.1%, 526/1 118)and perioperative mortality(0.5%, 5/1 118). After phone call following-up, 942 patients' long-term data were completed including 1, 3, 5 years postoperative upper gastrointestinal rebleeding rate(4.4%, 12.1%, 17.2%), 1, 3, 5-year postoperative survival rate(97.0%, 93.5%, 90.3%); the incidence of postoperative malignant tumors in 1, 3 and 5 years were 1.7%, 4.4% and 6.2%. Conclusions: Reasonable choosing of surgical indications and timing, proper performing the surgery process, effective conducting perioperative management of portal hypertension are directly related to the patient's short-term prognosis after portal hypertension. Surgical intervention can reduce the rates of patients with upper gastrointestinal rebleeding, improve survival, and do not increase the incidence of malignant tumors.

Cardiopulmonary resuscitation-from the patient's perspective.

With increasing emphasis on patient autonomy, patients are encouraged to be more involved in end-of-life issues, including the use of extraordinary efforts to prolong their lives. Being able to make anticipatory decisions is seen to promote autonomy, empower patients and optimise patient care. To facilitate shared decision-making, patients need to have a clear and accurate understanding of cardiopulmonary resuscitation (CPR). This study aims to understand the knowledge and perspectives of the local community regarding resuscitation options and end-of-life decision-making and to explore ways to improve the quality of end-of-life discussions. An interviewer-administered survey was conducted with a prospectively recruited group of surgical patients admitted postoperatively to the day surgery ward of a single tertiary institution in Singapore from April to May 2015. The survey, modelled after two validated questionnaires, measured patients' knowledge, attitudes and preferences regarding CPR in a series of 18 questions. Fifty-one out of 67 (76.1%) patients completed the survey. Results indicated that 80.4% (n=41) of participants correctly understood the purpose of CPR, but 64.7% (n=33) did not know of any possible complications of CPR. Less than half (n=21, 41.2%) of participants had thought about life support measures they wanted for themselves. Most of the participants agreed that they should personally be involved in making end-of-life decisions (n=44, 86.3%). Many patients had a poor knowledge of CPR and other resuscitation measures and the majority overestimated the success rate of CPR. However, a majority were receptive to improving their knowledge and keen to discuss end-of-life issues with physicians.

Differential expression profiling of microRNAs in para-carcinoma, carcinoma and relapse human pancreatic cancer.

PURPOSE: To explore the altered different expression of miRNAs and the mechanisms underlying the relapse and metastasis of pancreatic cancer. MATERIALS AND METHODS: The most differentially expressed miRNAs were analyzed by gene ontology (GO) term analysis, Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis and protein interaction analysis. The potentially regulated target genes of the most differentially expressed miRNAs were also analyzed further by GO term analysis and KEGG pathway analysis, and quantitated by qRT-PCR. RESULTS: In total, we found 12 miRNAs displayed at least a 30-fold increase or decrease in expression of carcinoma and relapse vs. para-carcinoma human pancreatic cancer (C/R vs. P). In addition, our study found that pancreatic cancer was related to pathways in cancer, including Jak-STAT signaling pathway, MAPK signaling pathway and PPAR signaling pathway. CONCLUSIONS: The differential expressed miRNAs and their predicted target genes that involved in Jak-STAT signaling pathway, MAPK signaling pathway and PPAR signaling pathway indicating their potential roles in pancreatic carcinogenesis and progress.

Doublets versus single-agent therapy as first-line therapy for elderly patients with advanced non-small cell lung cancer? A systematic review of randomised controlled trials.

INTRODUCTION: Although the standard treatment for advanced non-small cell lung cancer (NSCLC) patients is platinum-based doublet chemotherapy, single-agent therapy is still preferred in elderly patients. Comparison of the efficacy of various combinations of doublets with single-agent chemotherapy is somehow contradictory. This study conducted a systematic review to evaluate the efficacy and tolerability of the third-generation agent-based doublets vs. single-agent chemotherapy in elderly NSCLC patients. METHODS: Electronic (PubMed, EMBASE and Cochrane Library database) and manual searches were conducted to collect data from published, randomised, phase 2 and 3 trials which compared doublets with a third-generation single-agent chemotherapy in elderly patients. Pooled relative risks (RRs) were calculated for the incidences of overall response rate (ORR), 1-year survival rate (1-y SR), and grade 3/4 toxicities. RESULTS: Seven eligible trials (2219 patients) were selected from 1170 studies that were initially identified. A significant difference in ORR favouring doublets over single agents was observed [RR, 1.59; 95% confidence interval (95% CI), 1.36-1.86; p < 0.0001] with a slightly, but not significantly improved 1-y SR (RR, 1.19; 95% CI, 0.98-1.45, p = 0.007). Subgroup analysis suggested that platinum (RR, 1.94; 95% CI, 1.47-2.55, p < 0.0001) or non-platinum- (RR, 1.45; 95% CI, 1.20-1.75, p < 0.0001) based doublets could improve ORR, and the grade 3/4 thrombocytopaenia (RR, 6.64; 95% CI, 1.78-24.86, p = 0.005) and anaemia (RR, 2.86; 95% CI, 1.62-5.05, p < 0.0001) were preferred to occur in platinum-based doublets. CONCLUSIONS: Doublets appear to be more effective and tolerable than single-agent therapy for treating elderly advanced NSCLC patients, and therefore could be considered as a treatment option for elderly populations with good physical status.

Cyclophilin residues that affect noncompetitive inhibition of the protein serine phosphatase activity of calcineurin by the cyclophilin.cyclosporin A complex.

Mutation of three cationic surface residues of human cyclophilin A (hCyPA), R69, K125, and R148, to both anionic and neutral residues left its intrinsic peptidyl-prolyl isomerase (PPIase) activity and cyclosporin A (CsA) binding unaffected, but altered its ability to inhibit the serine phosphatase activity of calcineurin (CN). R69E was 13-fold less effective (Ki = 3400 nM) than wild-type hCyPA (Ki = 270 nM) in presenting CsA for calcineurin phosphatase inhibition, while R148E was 17-fold more effective (Ki < or = 16 nM), and human CyPB was 13-fold better (Ki < or = 21 nM), establishing that a composite drug/protein surface is being recognized. The phosphoserine phosphatase reaction catalyzed by CN using unlabeled phosphoserine RII19 peptide was coupled to a continuous spectrophotometric assay to measure inorganic phosphate production using the enzyme purine ribonucleoside phosphorylase and the substrate N7-methyl-2-thioguanosine [Webb, M. R. (1992) Proc. Natl. Acad. Sci. U.S.A. 89, 4884-4887]. With this assay, we have determined that human cyclophilin A complexed with the immunosuppressive drug cyclosporin A is a noncompetitive inhibitor of calcineurin phosphatase activity. This mutational analysis identified hCyPA residues that interact with CN, and comparison to similar data on FKBP allowed us to begin to map out the CN recognition surface. The p-nitrophenylphosphatase activity of CN was stimulated ca. 3-fold by CyP.CsA, presumably reflecting altered active site geometry and selective access of this small substrate.

Crystal structures of cyclophilin A complexed with cyclosporin A and N-methyl-4-[(E)-2-butenyl]-4,4-dimethylthreonine cyclosporin A.

BACKGROUND: Cyclophilin (CyP) is a ubiquitious intracellular protein that binds the immunosuppressive drug cyclosporin A (CsA). CyP-CsA forms a ternary complex with calcineurin and thereby inhibits T-cell activation. CyP also has enzymatic activity, catalyzing the cis-trans isomerization of peptidyl-prolyl amide bonds. RESULTS: We have determined the structure of human cyclophilin A (CyPA) complexed with CsA to 2.1 A resolution. We also report here the structure of CyPA complexed with an analog of CsA, CsA (MeBm2t1-CsA), which binds less well to CyPA, but has increased immunosuppressive activity. Comparison of these structures with previously determined structures of unligated CyPA and CyPA complexed with a candidate substrate for the isomerase activity, the dipeptide AlaPro, reveals that subtle conformational changes occur in both CsA and CyPA on complex formation. CONCLUSIONS: MeBm2t1-CsA binds to CyPA in an essentially similar manner to CsA. The 100-fold weaker affinity of its binding may be attributable to the close contact between MeBmt1 and the active site residue Ala103 of CyPA, which causes small conformational changes in both protein and drug. One change, the slight movement of MeLeu6 in CsA relative to MeBm2t1-CsA, may be at least partially responsible for the higher affinity of the CyPA-MeBm2t1-CsA complex for calcineurin. Our comparison between CyPA-CsA and CyPA-AlaPro suggests that CsA is probably not an analog of the natural substrate, confirming that the catalytic activity of CyPA is not related to its role in immunosuppression either structurally or functionally.

Deduced amino acid sequence of Escherichia coli adenosine deaminase reveals evolutionarily conserved amino acid residues: implications for catalytic function.

The goal of the research reported here is to identify evolutionarily conserved amino acid residues associated with enzymatic deamination of adenosine. To do this, we isolated molecular clones of the Escherichia coli adenosine deaminase gene by functional complementation of adenosine deaminase deficient bacteria and deduced the amino acid sequence of the enzyme from the nucleotide sequence of the gene. Nucleotide sequence analysis revealed the presence of a 996-nucleotide open reading frame encoding a protein of 332 amino acids having a molecular weight of 36,345. The deduced amino acid sequence of the E. coli enzyme has approximately 33% identity with those of the mammalian adenosine deaminases. With conservative amino acid substitutions the overall sequence homology approaches 50%, suggesting that the structures and functions of the mammalian and bacterial enzymes are similar. Additional amino acid sequence analysis revealed specific residues that are conserved among all three adenosine deaminases and four AMP deaminases for which sequence information is currently available. In view of previously published enzymological data and the conserved amino acid residues identified in this study, we propose a model to account for the enzyme-catalyzed hydrolytic deamination of adenosine. Potential catalytic roles are assigned to the conserved His 214, Cys 262, Asp 295, and Asp 296 residues of mammalian adenosine deaminases and the corresponding conserved amino acid residues in bacterial adenosine deaminase and the eukaryotic AMP deaminases.

Insulin insensitivity in offspring of parents with type 2 diabetes mellitus.

Measurements were made of the plasma glucose and insulin responses to a 75 g oral glucose challenge in 50 Chinese born in Taiwan, divided into two groups on the basis of family history of Type 2 diabetes. Twenty-five individuals (age 29 +/- 5 (+/- SD) years) had 2 parents with normal oral glucose tolerance, whereas at least 1 parent had Type 2 diabetes in the other 25 subjects (age 30 +/- 6 years). In addition, in vivo insulin action was estimated by determining the steady-state plasma glucose concentration during a 3-h continuous infusion of glucose, insulin, and somatostatin. Steady-state plasma glucose concentration was used as a measure of insulin-induced glucose disposal. The 50 subjects were non-obese, and of comparable gender distribution and body mass index. Plasma glucose and insulin concentrations in response to oral glucose were similar in the two groups. However, the steady-state plasma glucose concentration was significantly (p less than 0.01) higher in offspring with a family history of Type 2 diabetes when compared by two-way analysis of variance (mean +/- SE was 5.87 +/- 0.27 vs 5.12 +/- 0.32 mmol l-1). This difference was found despite a significantly (p less than 0.01) higher steady-state plasma insulin concentration during the infusion studies (0.705 +/- 0.027 vs 0.643 +/- 0.025 nmol l-1) in offspring of people with diabetes. The results support the view that resistance to insulin-stimulated glucose uptake is present in offspring of diabetic parents.