Clinicopathological characteristics and prognosis of 232 patients with poorly differentiated gastric neuroendocrine neoplasms

BACKGROUND Poorly differentiated gastric neuroendocrine neoplasms(PDGNENs)include gastric neuroendocrine carcinoma(NEC)and mixed adenoneuroendocrine carcinoma,which are highly malignant and rare tumors,and their incidence has increased over the past few decades.However,the clinicopathological features and outcomes of patients with PDGNENs have not been completely elucidated.AIM To investigate the clinicopathological characteristics and prognostic factors of patients with PDGNENs.METHODS The data from seven centers in China from March 2007 to November 2019 were analyzed retrospectively.RESULTS Among the 232 patients with PDGNENs,191(82.3%)were male,with an average age of 62.83±9.11 years.One hundred and thirteen(49.34%)of 229 patients had a stage III disease and 86(37.55%)had stage IV disease.Three(1.58%)of 190 patients had no clinical symptoms,while 187(98.42%)patients presented clinical symptoms.The tumors were mainly(89.17%)solitary and located in the upper third of the stomach(cardia and fundus of stomach:115/215,53.49%).Most lesions were ulcers(157/232,67.67%),with an average diameter of 4.66±2.77 cm.In terms of tumor invasion,the majority of tumors invaded the serosa(116/198,58.58%).The median survival time of the 232 patients was 13.50 mo(7,31 mo),and the overall 1-year,3-year,and 5-year survival rates were 49%,19%,and 5%,respectively.According to univariate analysis,tumor number,tumor diameter,gastric invasion status,American Joint Committee on Cancer(AJCC)stage,and distant metastasis status were prognostic factors for patients with PDGNENs.Multivariate analysis showed that tumor number,tumor diameter,AJCC stage,and distant metastasis status were independent prognostic factors for patients with PDGNENs.CONCLUSION The overall prognosis of patients with PDGNENs is poor.The outcomes of patients with a tumor diameter>5 cm,multiple tumors,and stage IV tumors are worse than those of other patients.

Clinicopathological characteristics and prognosis of 77 cases with type 3 gastric neuroendocrine tumours

BACKGROUND For the rarity of type 3 gastric neuroendocrine tumours(g-NETs),their clinicopathological characteristics and prognosis are not well illustrated.AIM To describe the clinicopathological features and outcome of type 3 g-NETs in the Chinese population.METHODS Based on the 2019 WHO pathological classification,the clinicopathological characteristics and prognosis of patients with type 3 g-NETs in China were retrospectively analysed.RESULTS A total of 77 patients(55.8%of females)with type 3 g-NETs were analysed,with a median age of 48 years(range:28-79 years).The tumours were mainly located in the gastric fundus/body(83.1%)and were mostly solitary(83.1%),with a median size of 1.5 cm(0.8-3.5 cm).Of these,there were 37 G1 tumours(48.1%),31 G2(40.3%),and 9 G3(11.7%).Ten(13.0%)and 24(31.2%)patients had lymph node and distant metastasis,respectively.In addition,type 3 g-NETs were heterogeneous.Compared with G1 NETs,G2 NETs had a higher lymph node metastasis rate,and G3 NETs had a higher distant metastasis rate.G1 and G2 NETs with stage I/II disease(33/68)received endoscopic treatment,and no tumour recurrence or tumour-related death was observed within a median follow-up time of 36 mo.Grade and distant metastasis were identified to be independent risk factors for prognosis in multivariable analysis.CONCLUSION Type 3 g-NETs are obviously heterogeneous,and the updated WHO 2019 pathological classification may be used to effectively evaluate their biological behaviors and prognosis.Also,endoscopic treatment should be considered for small(<2 cm),low grade,superficial tumours.

Hsa-miR-202-3p,up-regulated in type 1 gastric neuroendocrine neoplasms,may target DUSP1

AIM To detect abnormal micro RNA(miRNA) expression in type 1 gastric neuroendocrine neoplasms(g-NENs) and find potential target genes.METHODS Tumour tissues from patients with type 1 g-NENs were used as experimental samples, and gastric mucosal tissues from the same patients obtained during gastroscopy review after several months were used as control samples. miRNA expression was examined with Agilent human miRNA chips and validated via RTPCR. Three types of target gene prediction software(TargetScan, PITA, and microRNAorg) were used to predict potential target genes of the differentially expressed miRNAs, and a dual-luciferase reporter assay system was used for verification. RESULTS Six miRNAs were significantly upregulated or downregulated in the tumours compared to the control samples. Among them, miR-202-3 p was extraordinarily upregulated. RT-PCR of seven sample sets confirmed that miR-202-3 p was upregulated in tumour tissues. In total, 215 target genes were predicted to be associated with miR-202-3 p. Among them, dual-specificity phosphatase 1(DUSP1) was reported to be closely related to tumour occurrence and development. The dual-luciferase reporter assay showed that miR-202-3 p directly regulated DUSP1 in 293 T cells. CONCLUSION miR-202-3 p is upregulated in type 1 g-NEN lesions and might play important roles in the pathogenesis of type 1 g-NENs by targeting DUSP1.

Advances in medical treatment for pancreatic neuroendocrine neoplasms

Pancreatic neuroendocrine neoplasms(PanNENs)are rare neoplasms with strong heterogeneity that have experienced an increasing incidence rate in recent years.For patients with locally advanced or distant metastatic PanNENs,systemic treatment options vary due to the different differentiations,grades and stages.The available options for systemic therapy include somatostatin analogs,molecularly targeted agents,cytotoxic chemotherapeutic agents,immune checkpoint inhibitors,and peptide receptor radionuclide therapy.In addition,the development of novel molecularly targeted agents is currently in progress.The sequence of selection between different chemotherapy regimens has been of great interest,and resistance to chemotherapeutic agents is the major limitation in their clinical application.Novel agents and high-level clinical evidence continue to emerge in the field of antiangiogenic agents.Peptide receptor radionuclide therapy is increasingly employed for the treatment of advanced neuroendocrine tumors,and greater therapeutic efficacy may be achieved by emerging radiolabeled peptides.Since immune checkpoint inhibitor monotherapies for PanNENs appear to have limited antitumor activity,dual immune checkpoint inhibitor therapies or combinations of antiangiogenic therapies and immune checkpoint inhibitors have been applied in the clinic to improve clinical efficacy.Combining the use of a variety of agents with different mechanisms of action provides new possibilities for clinical treatments.In the future,the study of systemic therapies will continue to focus on the screening of the optimal benefit population and the selection of the best treatment sequence strategy with the aim of truly achieving individualized precise treatment of PanNENs.

Investigation into PCB Routing Loss for Coupled Inductor Based VR (Voltage Regulator) Design in Server Computing System

Coupled inductor is one appealing technology to improve transient response and reduce output decoupling significantly in interleaved multi-phase voltage regulators (VRs). One well known problem is that coupled inductor winding structure causes PCB routing path longer than discrete inductor design. This paper investigates possible PCB routing schemes for coupled inductor and conducts a fair and quantitative comparison with discrete inductor in a server VR design. Simulation and measurement are also conducted to verify the analysis.

Predicting Individual Phase Current in Couple Inductor Based Voltage Regulators (VRs)

Coupled inductor is one appealing technology to improve transient response and reduce output decoupling significantly in interleaved multi-phase voltage regulators (VRs). One known problem is that there is no mature solution yet to sense the individual phase current accurately in a lossless way for couple inductor based VRs design. This will impact VR some normal function in one phase mode. This paper proposes a new solution to this problem and simulation is conducted to verify effectiveness of the proposal.

Relationship between Crystal Structure of Inclusions and Formation of Acicular Ferrites

The formation mechanism of intragranular ferrites with acicular morphology was discussed.The ferrites were characterized by scanning electron microscopy.The results showed that the ferrites had an acicular structure with radial,symmetrical,and acicular laths,and that the inclusions were the nucleation sites of the intragranular acicular ferrites.Transmission electron microscopy（TEM）was used to characterize the inclusions.The results of TEM with energy dispersive spectroscopy and TEM-selected area electron diffraction indicated that the complex inclusions consisted of Ti-Al complex oxides and MnS.The jagged edges of the complex inclusions can be ascribed to the effects of the crystal structure.The stabilization energy U of the coordination polyhedron growth units varies with the type of connection according to the calculation results.A larger Ucorresponds to more stable growth units,which induces the preferentially oriented growth of inclusions,at which point acicular ferrites are formed.