Consensus and controversy of endoscopic diagnosis and treatment of gastroenteropancreatic neuroendocrine tumors / 中华胃肠外科杂志

Neuroendocrine neoplasms(NENs) are relatively rare tumors originating from the diffuse neuroendocrine system, and gastrointestinal tract is one of the most common location of the tumors. Currently, the European Neuroendocrine Neoplasm Society (ENETS) and the National Comprehensive Cancer Network (NCCN) have released the international guidelines for NENs management. And also, experts from Chinese Society of Clinical Oncology (CSCO) have proposed "The Consensus on Gastroenteropancreatic Neuroendocrine Neoplasm in China" in 2016, which is also one of the most important reference standard for the diagnosis and treatment of gastroenteropancreatic(GEP) NENs in China. Here we will interpret these three guidelines or consensus. There are few controversies about endoscopic management principle for GEP-NEN of different locations and sizes among these three guidelines or consensus, but for small NENs without involving intrinsic muscularis, endoscopic resection is recommended and considered. We hope that this interpretation may help clinicians for clinical decision making.

Analysis of genetic mutations and pathogenesis for two children with Omenn syndrome / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To explore the clinical characteristics and genetic mutations in two children with Omenn syndromes.</p><p><b>METHODS</b>Peripheral venous blood samples were collected from 2 children suspected with severe combined immunodeficiency (SCID) and their family members. The samples were subjected to RAG1 and RAG2 gene sequencing and TCR Vβ subclone analysis.</p><p><b>RESULTS</b>Both patients had recurrent infections, erythroderma rashes and alopecia baldness. One patient has fit with immunophenotype T-B-NK+, while another was consistent with typical Omenn syndrome combined with T+B-NK+ immunophenotype, IgE and eosinophil increase. Both children have carried compound heterozygous mutations of the RAG1 gene. The first patient carried c.1328 G>A (p.R443K) and c.2486-2490delGGAAA (p.R829fsX869) mutations, both were of de novel type. The second patient has carried c.1209C>T (p.R403W) and c.2892delT (p.ASN964LYSfs*14), with c.2892delT (p.ASN964LYSfs*14) being a de novel mutation. The parents of both patients were heterozygous carriers. The same mutations were not found in 100 healthy children. Both patients' 24 TCR Vβ subfamilies have presented monoclonal or oligoclonal peaks, with TCR Vβ polymorphism being severely disrupted.</p><p><b>CONCLUSION</b>Three novel mutations have been identified in two children with Omenn syndrome, which featured early onset and rapid progression. Early recognition of the disease and prompt treatment may reduce the mortality.</p>

Establishment of risk model for predicting the progression within 1 year of patients with gastric neuroendocrine neoplasms and its value of prediction / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To establish the risk model for predicting the progression within 1 year of patients with gastric neuroendocrine neoplasms(gNEN) and to evaluate its value of prediction.</p><p><b>METHODS</b>Clinical data of 127 gENE patients with histologically comfirmed sporadic gNEN from January 1999 to February 2015 in Nanfang Hospital of Southern Medical University(n=63) and The First Affiliated Hospital of Sun Yat-sen University(n=64) were collected retrospectively. Twenty-five patients without follow-up were excluded, so a total of 102 cases were enrolled in the analysis. Tumor size enlargement, lesion number increase, recurrence after resection of primary tumor and emergence of tumor metastasis were defined as tumor progression. Patients were divided into progression group (above definitions occurred within 1 year, n=56) and non-progression group (above definitions did not occur within 1 year, n=46). Logistic regression analysis was used to identify the influencing factors of progression within 1 year and the regression equation was acquired, then the probability of progression within 1 year of gNEN patients was obtained to predict the grading: grade I(: the probability of tumor progression within 1 year was < 25.0%; grade II(: this probability was from ≥25.0% to <50.0%; grade III(: this probability was from ≥50.0% to <75.0%; grade IIII(:this probability was ≥75.0%. Spearman correlation analysis was used to study the correlation between predictive grading and the occurrence of disease progression in patients with gNEN NET within 1 years. The ROC curve of different prediction methods was drawn, then the area under the curve(AUC), sensitivity and specificity were calculated and compared.</p><p><b>RESULTS</b>Multivariate regression analysis showed that tumor size(OR=1.048, 95%CI:1.014-1.083, P=0.005), Ki-67 index(OR=2.045, 95%CI:1.261-3.316, P=0.004), and surgical resection of the primary lesion(OR=0.074, 95%CI:0.011-0.497, P=0.070) were independent influencing factors of the progression of gNET within 1 year. The regression equation was as below: P(Y)=1/[1+ e -(-0.934+0.047a+0.715b-2.597c)]. (a: tumor size, b: Ki-67 grading, c: undergoing the surgical resection of the primary lesion). Prediction grading was based on regression equation: 28 cases (29.2%) belonged to grade I(, 9 cases (9.4%) to grade II(, 24 cases (25.0%) to grade III(, and 35 cases (36.5%) to grade IIII(. The probability of progression within 1 year of patients in grade I(, II(, III( and IIII( was 10.7% (3/28),5/9, 58.3%(14/24), and 91.4%(32/35) respectively, with significant difference (χ=41.236, P=0.000). Prediction grading was positively correlated with the occurrence of tumor progression in gNEN patients within 1 year(r=0.644, P=0.000). The AUC of prediction grading to predict the progression of gNEN within 1 year was 0.857, while the sensitivity was 85.2% and the specificity was 69.0%. DeLong method was used to compare the AUC values of prediction grading, Ki-67 grading and TNM staging. Comparison result revealed that the predictive value of prediction grading was not significantly different with that of TNM staging (P=0.303), but was better than that of Ki-67 grading (P=0.006).</p><p><b>CONCLUSIONS</b>Our grading standard can objectively and accurately reflect the probability of progression within one year in gNEN patients. The later the grading, the higher the probability of progression within 1 year is for gNEN patients.</p>

Interleukin-10 receptor mutations in children with neonatal onset inflammatory bowel disease: genetic diagnosis and pathogenesis / 中华儿科杂志

<p><b>OBJECTIVE</b>To explore use of interleukin-10 receptor (IL-10R) gene mutation in diagnosis and pathogenesis of neonatal inflammatory bowel disease (IBD) in 2 suspected cases.</p><p><b>METHOD</b>Two cases of sibling brothers who had suspected IBD from Guangzhou Women and Children's Medical Center Affiliated to Guangzhou Medical University during the year 2010-2014 were enrolled in the study. The proband, male, 26 days old, weight 3.73 kg, presented with recurrent fever, increased stool frequency since 9 days of age, and was hospitalized at the age of 6 months in 2014. The proband's brother, male, 6 months old, weight 8 kg, had repeated bloody and mucous diarrhea for more than five months, recurrent fever five days, and was hospitalized in 2010. The blood samples were collected from the children and their families for IL-10 receptor genes including IL-10 receptor α subunit (IL-10RA) and β subunit (IL-10RB) PCR amplification. Reverse transcription polymerase chain reaction (RT-PCR) was used to amplify the proband IL-10RA transcripts. Sequencing was performed on the PCR products forward and reversely. Western blot analysis was used for protein expression of the proband and normal control's IL-10RA and P-STAT3 (Tyr705) expression after IL-10 stimulation, TNF-α level was detected using Human TNF-α ELISA Kit after PBMC was cultured and stimulated.</p><p><b>RESULT</b>The proband and his brother were IBD patients. Genome sequencing showed mutation in c.537G>A, namely the exon 4 and intron 4 connections changed CA/GT for CG/GT. Sequencing of the RT-PCR products and T-A clone showed that the mutation was (c.519-537del GGTGCCGGGAAACTTCAC, p.LYS173ASNfs*7), as the splice mutation. Two gene mutations were novel mutation. The parents were the mutations carrier. Both of the children were compound heterozygous mutations in IL-10RA. The Western blot analysis showed that the patient and normal children can express IL-10RA protein, however, the function of IL-10RA had obvious defects in the patient, IL-10RA downstream signaling pathways P-STAT3 had no expression. The average level of TNF-α secreted by PBMC after LPS + IL-10 co-stimulation in patient was significantly increased as compared with control group ((2 100±356) vs. (200±50) ng/L, t=9.154, P=0.001), suggesting that interleukin-10-dependent negative feedback regulation is disrupted in the patient.</p><p><b>CONCLUSION</b>IL-10 receptor mutations can cause neonatal-IBD, for which common treatment effect is poor. Early diagnosis and allogeneic stem-cell transplantation performed may save the children's life.</p>