Pregnancy and Progression of Differentiated Thyroid Cancer: A Propensity Score-Matched Retrospective Cohort Study.

CONTEXT AND OBJECTIVE: Differentiated thyroid cancer (DTC) is very common in women of reproductive age. However, it remains unclear whether pregnancy is associated with DTC progression before surgical treatment. METHODS: This retrospective cohort study, conducted at the Peking University Third Hospital in Beijing, China between January 2012 and December 2022, included 311 eligible women aged 20 to 45 years. To control for potential confounders, we first used propensity score matching (PSM) to match the pregnant group (n = 48) with the nonpregnant group (n = 154) on age, tumor size, tumor type, and Hashimoto's thyroiditis status at baseline, and then used Cox proportional risk models stratified by the matched pairs to estimate the association of pregnancy with DTC progression. RESULTS: After PSM, the pregnant and nonpregnant groups were well comparable at baseline (standardized difference < 10% and P > .05). Over an average observation period of 2.5 years, we observed no difference between the pregnant group and the matched nonpregnant group in DTC progression-free survival (hazard ratio [HR] = 0.96; 95% CI, 0.56 to 1.65; P = .895), tumor enlargement-free survival (HR = 0.99; 95% CI, 0.56 to 1.76; P = .969) or lymph node metastasis-free survival (LNM) (HR = 0.67; 95% CI, 0.21 to 2.13; P = .498). The postoperative pathological characteristics also showed no significant difference between the pregnant and nonpregnant groups (P > .05). CONCLUSION: Pregnancy seemed to be irrelevant to DTC progression-free survival before surgical treatment. Further prospective cohort studies are needed to translate this finding into clinical practice.

The Association of Pregnancy with Disease Progression in Patients Previously Treated for Differentiated Thyroid Cancer: A Propensity Score-Matched Retrospective Cohort Study.

Background: Differentiated thyroid cancer (DTC) is increasingly common in women of reproductive age. However, whether pregnancy increases the risk of DTC progression/recurrence after treatment remains controversial. The study aimed to assess the association of pregnancy with risk of progression in patients previously treated for DTC. Methods: This was a retrospective cohort study following 123 pregnant women and 1376 nonpregnant women at Peking University Third Hospital after initial treatment for DTC between January 2012 and December 2022. To control the effect of confounding, we carefully matched pregnancy (n = 107) and nonpregnancy groups (n = 298) in terms of baseline characteristics by using propensity score matching (PSM). Results: At baseline, the pregnancy and nonpregnancy groups were balanced in all matched variables. At follow-up, the percentage of DTC progression in the two groups was 12 (11.8%) and 47 (15.8%), respectively. Regression models showed no evidence of association of pregnancy with the risk of progression (odds ratio: 0.74 and 95% confidence interval: 0.37-1.50; p = 0.404), and remained consistent across long/short follow-up and other subgroup variables. We found that the shorter the time interval between treatment and pregnancy, the higher the risk of DTC progression (ptrend = 0.019). Conclusions: The risk of DTC progression in pregnant women was not higher than that in the well-matched, nonpregnant women. For young women previously treated for DTC, disease progression might not be a concern for their future pregnancy plan, but it seems safer to wait at least 1 year before pregnancy compared with immediate pregnancy.

The Overexpression of SLC25A13 Predicts Poor Prognosis and Is Correlated with Immune Cell Infiltration in Patients with Skin Cutaneous Melanoma.

Purpose: Skin cutaneous melanoma (SKCM) is one of the most malignant and aggressive cancers with poor prognosis due to its rapid progression towards metastasis. Thus, finding clinically relevant biomarkers for early diagnosis, prognosis, and therapy prediction is essential. This study focused on the identification of SLC25A13 as a novel biomarker for SKCM and is aimed at investigating the biological functions of solute carrier family 25 member 13 (SLC25A13) in the development of SKCM. Methods: GEPIA was used to analyze the diagnostic and prognostic values of SLC25A13 in SKCM using the TCGA dataset. PrognoScan was used to validate the prognostic value of SLC25A13 and its coexpressed genes in SKCM. TISIDB was established to reveal the relationship between the expression of SLC25A13 and immune infiltration in SKCM. The protein expression of SLC25A13 in SKCM was evaluated by the Human Protein Atlas. The signaling pathways and biological functions of SLC25A13 in SKCM were analyzed by LinkOmics. Metascape was applied to analyze the functional enrichment analysis of SLC25A13. Protein-protein interaction analysis of SLC25A13 was performed by GeneMANIA. Results: The mRNA and protein levels of SLC25A13 in the SKCM were much higher than those in the normal tissue. Furthermore, the overexpression of SLC25A13 predicts worse outcomes of SKCM patients. Moreover, the SLC25A13 expression was negatively correlated with the immune infiltration level of SKCM. The overexpression of SLC25A13 coexpressed genes, such as ACLY and AFG3L2, and SCL25A13 interacting genes also predicted the unfavorable prognosis of SKCM patients. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of SLC25A13 coexpressed genes showed that these genes are enriched in ATPase activity, cell cycle, mTOR, and VEGFA-VEGFR2 signaling pathways, which were relevant to tumor development and angiogenesis. Gene set enrichment analysis (GSEA) demonstrated that the SLC25A13 expression was related to infiltrating immune cells in SKCM. Conclusion: Our findings revealed that SLC25A13 might be a potential prognostic and therapeutic biomarker for SKCM.

Application of Magnetic Resonance Imaging in Neoadjuvant Treatment of Pancreatic Ductal Adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest malignant tumors of the human digestive system. Due to its insidious onset, many patients have already lost the opportunity for radical resection upon tumor diagnosis. In recent years, neoadjuvant treatment for patients with borderline resectable PDAC has been recommended by multiple guidelines to increase the resection rate of radical surgery and improve the postoperative survival. However, further developments are required to accurately assess the tumor response to neoadjuvant therapy and to select the population suitable for such treatment. Reductions in drug toxicity and the number of neoadjuvant cycles are also critical. At present, the clinical evaluation of neoadjuvant treatment is mainly based on several serological and imaging indicators; however, the unique characteristics of PDAC and the insufficient sensitivity and specificity of the markers render this system ineffective. The imaging evaluation system, magnetic resonance imaging (MRI), has its own unique imaging advantages compared with computed tomography (CT) and other imaging examinations. One key advantage is the ability to reflect the changes more rapidly in tumor tissue components, such as the degree of fibrosis, microvessel density, and tissue hypoxia. It can also perform multiparameter quantitative analysis of tumor tissue and changes, attributing to its increasingly important role in imaging evaluation, and potentially the evaluation of neoadjuvant treatment of pancreatic cancer, as several current articles have studied. At the same time, owing to the complexity of MRI and some of its limitations, its wider application is limited. Compared with CT imaging, few relevant studies have been conducted. In this review article, we will investigate and summarize the advantages, limitations, and future development of MRI in the evaluation of neoadjuvant treatment of PDAC. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 2.

Should Positive Cytology Revealed by Intraoperative Lavage Preclude Radical Resection in Resectable Pancreatic Cancer?: A Systemic Review and Meta-analysis.

OBJECTIVES: The aims of this review were to determine whether positive peritoneal lavage cytology (CY+) precludes radical resection in pancreatic cancer and to propose prospections for future studies. METHODS: MEDLINE, Embase, and Cochrane Central were searched for related articles. Dichotomous variables and survival outcomes were analyzed with the estimation of odds ratio and hazards ratio (HR), respectively. RESULTS: A total of 4905 patients were included, of which 7.8% were CY+. Positive peritoneal lavage cytology was correlated with poor overall survival (univariate survival analysis [HR, 2.35; P < 0.00001]; multivariate analysis [HR, 1.62; P < 0.00001]), poor recurrence-free survival (univariate survival analysis [HR, 2.50; P < 0.00001]; multivariate analysis [HR, 1.84; P < 0.00001]), and higher initial peritoneal recurrence rate (odds ratio, 5.49; P < 0.00001). CONCLUSIONS: Although CY+ predicts poor prognosis and a higher risk of peritoneal metastasis after curative resection, it is not sufficient to preclude curative resection based on the current evidence, and high-quality trials should be conducted to assess the prognostic impact of operation among resectable CY+ patients. In addition, more sensitive and accurate methods to detect peritoneal exfoliated tumor cells and more effective comprehensive treatment for resectable CY+ pancreatic cancer patients are clearly warranted.

Using a Nomogram to Preoperatively Predict Distant Metastasis of Pancreatic Neuroendocrine Tumor in Elderly Patients.

Objective To establish a nomogram for predicting the distant metastasis risk of pancreatic neuroendocrine tumors (pNETs) in elderly patients. Methods We extracted data of patients with diagnosis of pNETs at age ≥65 years old between 1973 and 2015 from the Surveillance, Epidemiology, and End Results (SEER) database. All eligible patients were divided randomly into a training cohort and validation cohort. Uni- and multivariate logistic regression analyses were performed on the training cohort to identify independent factors for distant metastasis. A nomogram was developed based on the independent risk factors using rms packages of R software, and was validated internally by the training cohort and externally by the validation cohort using C-index and calibration curves. Results A total of 411 elderly patients were identified, of which 260 were assigned to training cohort and 151 to validation cohort. Univariate and multivariate logistic regression analyses indicated the tumor site (body/tail of pancreas: odds ratio [OR]=2.282; 95% confidence interval [CI]: 1.174 - 4.436, P<0.05), histological grade (poorly differentiated/undifferentiated: OR=2.600, 95% CI: 1.266-5.339, P<0.05), T stage (T2: OR=8.913, 95% CI: 1.985-40.010, P<0.05; T3: OR=11.830, 95% CI: 2.530-55.350, P<0.05; T4: OR=68.650, 95% CI: 8.020-587.600, P<0.05), and N stage (N1: OR=3.480, 95% CI: 1.807-6.703, P<0.05) were identified as independent risk factors for distant metastasis of pNETs in elderly. The nomogram exhibited good predicting accuracy, with a C-index of 0.809 (95% CI: 0.757 - 0.861) in internal validation and 0.795 (95% CI: 0.723 - 0.867) in external validation, respectively. The predicted distant metastasis rates were in satisfactory agreement with the observed values by the calibration curves. Conclusion The nomogram we established showed high discriminative ability and accuracy in evaluation of distant metastasis risk in elderly pNETs patients, and could provide a reference for individualized tumor evaluation and treatment decision in elderly pNETs patients.

Nomogram and competing risk model to predict recurrence after curative surgical resection of PDAC.

BACKGROUND: Surgical resection remains the only potentially curative treatment for pancreatic ductal adenocarcinoma (PDAC). However, a number of patients get disease recurred in a short time post-operation. Few studies have focused on the predictors of different recurrence patterns of PDAC. OBJECTIVE: To try to establish and verify a nomogram to predict recurrence free survival (RFS) in PDAC patients, and to distinguish the risk factors of local recurrence first and distant metastasis first via competing risk model. METHODS: Patients who underwent radical pancreatectomy for PDAC in our center from 2010 to 2018 were reviewed retrospectively. Kaplan-Meier methods and multivariate Cox regression analyses were used to identify the clinicopathological predictors of recurrence post-operation. And then, a nomogram was constructed and validated. Competing risk regression model was used to compare the predictors between local recurrence group and distant metastasis group. RESULTS: A total of 200 patients were included into the final analysis, and 153 patients got disease relapsed post-operation. CA19-9 level, vascular resection, tumor differentiation, lymph node ratio (LNR) and adjuvant chemotherapy were identified as independent risk factors for recurrence free survival (RFS) and incorporated into the nomogram. The C-index of the nomogram was 0.650. Competing risk model indicated that the status of lymph-node metastasis was significantly associated the patterns of first relapse. CONCLUSIONS: Nomogram and competing risk model were constructed to quantify the risk of recurrence following surgery for PDAC. Our findings may be useful for predicting RFS and recurrence pattern in clinical work.

Establishment of a Macrophage Phenotypic Switch Related Prognostic Signature in Patients With Pancreatic Cancer.

INTRODUCTION: Macrophage phenotype switch plays a vital role in the progression of malignancies. We aimed to build a prognostic signature by exploring the expression pattern of macrophage phenotypic switch related genes (MRGs) in the Cancer Genome Atlas (TCGA)-pancreatic adenocarcinoma (PAAD), Genotype-Tissue Expression (GTEx)-Pancreas, and Gene Expression Omnibus (GEO) databases. METHODS: We identified the differentially expressed genes between the PAAD and normal tissues. We used single factor Cox proportional risk regression analysis, Least Absolute Shrinkage and Selection Operator (LASSO) analysis, and multivariate Cox proportional hazard regression analysis to establish the prognosis risk score by the MRGs. The relationships between the risk score and immune landscape, "key driver" mutations and clinicopathological factors were also analyzed. Gene-set enrichment analysis (GSEA) analysis was also performed. RESULTS: We detected 198 differentially expressed MRGs. The risk score was constructed based on 9 genes (KIF23, BIN1, LAPTM4A, ERAP2, ATP8B2, FAM118A, RGS16, ELMO1, RAPGEFL1). The median overall survival time of patients in the low-risk group was significantly longer than that of patients in the high-risk group (P < 0.001). The prognostic value of the risk score was validated in GSE62452 dataset. The prognostic performance of nomogram based on risk score was superior to that of TNM stage. And GSEA analysis also showed that the risk score was closely related with P53 signaling pathway, pancreatic cancer and T cell receptor signaling pathway. qRT-PCR assay showed that the expressions of the 9 MRGs in PDAC cell lines were higher than those in human pancreatic ductal epithelium cell line. CONCLUSIONS: The nine gene risk score could be used as an independent prognostic index for PAAD patients. Further studies validating the prognostic value of the risk score are warranted.

KLHDC7B-DT aggravates pancreatic ductal adenocarcinoma development via inducing cross-talk between cancer cells and macrophages.

Tumor microenvironment (TME) exerts key roles in pancreatic ductal adenocarcinoma (PDAC) development. However, the factors regulating the cross-talk between PDAC cells and TME are largely unknown. In the present study, we identified a long noncoding RNA (lncRNA) KLHDC7B divergent transcript (KLHDC7B-DT), which was up-regulated in PDAC and correlated with poor survival of PDAC patients. Functional assays demonstrated that KLHDC7B-DT enhanced PDAC cell proliferation, migration, and invasion. Mechanistically, KLHDC7B-DT was found to directly bind IL-6 promoter, induce open chromatin structure at IL-6 promoter region, activate IL-6 transcription, and up-regulate IL-6 expression and secretion. The expression of KLHDC7B-DT was positively correlated with IL-6 in PDAC tissues. Via inducing IL-6 secretion, KLHDC7B-DT activated STAT3 signaling in PDAC cells in an autocrine manner. Furthermore, KLHDC7B-DT also activated STAT3 signaling in macrophages in a paracrine manner, which induced macrophage M2 polarization. KLHDC7B-DT overexpressed PDAC cells-primed macrophages promoted PDAC cell proliferation, migration, and invasion. Blocking IL-6/STAT3 signaling reversed the effects of KLHDC7B-DT on macrophage M2 polarization and PDAC cell proliferation, migration, and invasion. In conclusion, KLHDC7B-DT enhanced malignant behaviors of PDAC cells via IL-6-induced macrophage M2 polarization and IL-6-activated STAT3 signaling in PDAC cells. The cross-talk between PDAC cells and macrophages induced by KLHDC7B-DT represents potential therapeutic target for PDAC.

Does Prior Cancer Have an Influence on the Survival Outcomes of Patients with Localized Pancreatic Neuroendocrine Tumors?

Objective To investigate the impact of prior non-pancreatic cancer on the survival outcomes of patients with localized pancreatic neuroendocrine tumors (PanNETs). Methods We reviewed the Surveillance, Epidemiology, and End Results database and selected patients with localized PanNETs diagnosed between 1973 and 2015. We divided the patients into two groups according to the presence or absence of prior non-pancreatic malignancy. Before and after propensity score matching, we compared the clinicopathological characteristics and studied the overall survival and cancer-specific survival. Results A total of 357 (12.9%) of 2778 patients with localized PanNETs had prior cancer. A total of 1211 cases with only a localized PanNET and 133 cases with a localized PanNET and prior cancer had complete data and met the inclusion criteria of the current study. Patients with prior cancer were associated with advanced age (>65 years, 57.9% prior cancer vs. 31.0% no prior cancer, P<0.001), later year of diagnosis (87.2% vs. 80.2%, P=0.049), a higher proportion of poorly differentiated/undifferentiated grade tumors (4.5% vs. 1.5%, P=0.025), and a higher proportion of no primary site surgery (19.5% vs. 10.4%, P=0.003). Prostate (29.32%), breast (18.05%), other genitourinary and retroperitoneal (16.54%), and gastrointestinal (12.78%) cancers were the most common prior cancer types. Most of the prior cancers (95.49%) were localized and regional, and only 4.51% of the prior cancers were distant. Patients with interval periods between the prior cancer and PanNET of ≤36 months, 36-60 months, 60-120 months, and >120 months accounted for 33.08%, 13.53%, 24.06%, and 29.32% of all cases with prior cancers, respectively. Univariate and multivariate Cox proportional hazards analyses were performed. The presence/absence of prior cancers did not impact survival outcomes of patients with localized PanNETs before and after propensity score matching (PSM). Further subgroups analysis showed that, patients with localized PanNETs and prior distant cancer had worse cancer-specific survival than patients with prior local/regional cancer or patients without prior cancer (P<0.001). No significant differences in cancer-specific survival were observed in terms of the different sites of the prior cancers and the different interval periods of prior cancers and PanNETs (P<0.05). Conclusions Patients with localized PanNETs and a history of prior cancer had survival outcomes that were comparable to those of patients with no history of prior cancer. Patients with localized PanNETs and prior cancer could be candidates for clinical trials if they satisfy all other conditions; aggressive and potentially curative therapies should be offered to these patients.

The eighth version of American Joint Committee on Cancer nodal classification for high grade pancreatic neuroendocrine tumor should be generalized for the whole population with this disease.

Several indexes evaluating the lymph node metastasis of pancreatic neuroendocrine tumor (pNET) have been raised. We aimed to compare the prognostic value of the indexes via the analysis of Surveillance, Epidemiology, and End Results (SEER) database.We identified pNETs patients from SEER database (2004-2015). The prognostic value of N classification which adopted the 8th American Joint Committee on Cancer (AJCC) N classification for well differentiated pNET, revised N classification (rN) which adopted the AJCC 8th N classification for exocrine pancreatic cancer (EPC) and high grade pNET, lymph node ratio and log odds of positive nodes were analyzed.A total of 1791 eligible patients in the SEER cohort were included in this study. The indexes N, rN, lymph node ratio, and log odds of positive nodes were all significant independent prognostic factors for the overall survival. Specifically, the rN had the lowest akaike information criterion of 4050.19, the highest likelihood ratio test (χ) of 48.87, and the highest C-index of 0.6094. The rN was significantly associated with age, tumor location, tumor differentiation, T classification and M classification (P < .05 for all).The 8th version of AJCC N classification for high grade pNET could be generalized for the pNET population.

Impact of a Prior Nonpancreatic Malignancy on Survival Outcomes of Patients With Stage IV Pancreatic Neuroendocrine Tumor: A Population-Based and Propensity Score Matching Study.

OBJECTIVE: The aim of the study was to investigate the impact of a previous nonpancreatic malignancy on the survival outcomes in patients with a stage IV pancreatic neuroendocrine tumor (PanNET). METHODS: The Surveillance, Epidemiology, and End Results database was reviewed, and patients diagnosed with a stage IV PanNET between 2004 and 2015 were selected. Patients were divided into 2 groups according to the presence or absence of a previous nonpancreatic malignancy. Clinicopathological characteristics and survival outcomes were compared. RESULTS: A total of 1582 patients with stage IV PanNET were identified, of whom 116 (7.3%) had a prior malignancy. Prostate (33.62%), breast (17.24%), and gastrointestinal (12.07%) malignancies were the most common. Most prior malignancies (84.48%) were localized and regional. Patients with intervals of 36 months or less, 36 to 60 months, 60 to 120 months, and more than 120 months account for 25.86%, 14.66%, 31.03%, and 28.45% of all cases, respectively. Before and after propensity score matching, there was no significant difference detected regarding survival outcomes. CONCLUSIONS: Stage IV PanNET patients with a history of a prior cancer had comparable survival outcomes with patients without such history. These patients could be candidates for clinical trials if otherwise appropriate, and aggressive and potentially curative therapies should be offered.

Pancreatic ductal adenocarcinoma immune microenvironment and immunotherapy prospects.

The tumor microenvironment of pancreatic ductal adenocarcinoma (PDAC) is non-immunogenic, which consists of the stellate cells, fibroblasts, immune cells, extracellular matrix, and some other immune suppressive molecules. This low tumor perfusion microenvironment with physical dense fibrotic stroma shields PDAC from traditional antitumor therapies like chemotherapy and various strategies that have been proven successful in other types of cancer. Immunotherapy has the potential to treat minimal and residual diseases and prevent recurrence with minimal toxicity, and studies in patients with metastatic and nonresectable disease have shown some efficacy. In this review, we highlighted the main components of the pancreatic tumor microenvironment, and meanwhile, summarized the advances of some promising immunotherapies for PDAC, including checkpoint inhibitors, chimeric antigen receptors T cells, and cancer vaccines. Based on our previous researches, we specifically discussed how granulocyte-macrophage colony stimulating factor based pancreatic cancer vaccine prime the pancreatic tumor microenvironment, and introduced some novel immunoadjuvants, like the stimulator of interferon genes.

Nomograms predict survival outcomes for distant metastatic pancreatic neuroendocrine tumor: A population based STROBE compliant study.

As a rare malignant tumor, pancreatic neuroendocrine tumor (pNET) has very low incidence. However, most of the pNET patients would develop the distant metastasis, which significantly reduces patients' survival rate. Therefore, it is very important to construct a prognostic model of pNET patients with distant metastasis based on a large database to guide clinical application and treatment. The aim of this study is to establish nomograms for cancer-specific survival (CSS) and overall survival (OS) of patients with distant metastatic pNET based on the Surveillance, Epidemiology, and End Results (SEER) database.SEER were reviewed and the patients with pNET diagnosed between 1973 and 2015 were selected. After screening, a total of 624 cases were included in the study. Patients were randomly divided into a training cohort (n = 416) and a validation cohort (n = 208). Cox proportional hazard analysis revealed that age at diagnosis of ≥80 years, year of diagnosis, histological grade, and primary site surgery were independent factors both for CSS and OS. The nomograms indicated good accuracy in predicting 1-, 3-, and 5-year survival, with a C-index of 0.777 (95% confidence interval [CI], 0.743-0.811) for CSS and 0.772 (95% CI 0.738-0.806) for OS in training cohort. In the validation cohort, the C-index was 0.798 (95% CI 0.755-0.841) for CSS and 0.797 (95% CI 0.753-0.841) for OS. The calibration curves showed satisfactory consistency between predicted and actual survival.The study establishes excellent prognostic nomograms for CSS and OS for pNET patients with distant metastasis. They can be used to accurately predict survival rate, and provide useful information to physicians and patients.

Secreted Rv1768 From RD14 of Mycobacterium tuberculosis Activates Macrophages and Induces a Strong IFN-γ-Releasing of CD4+ T Cells.

As the first line defensive mediators against Mycobacterium tuberculosis (M.tb) infection, macrophages can be modulated by M.tb to influence innate and adaptive immunity. Recently, we have identified several potential immunodominant T-cell antigens from the region of deletion (RD) of M.tb H37Rv, including Rv1768 from RD14. In this study, we further determined that Rv1768 was highly conserved among virulent M.tb strains and mainly distributed as a secreted protein. Exposure to recombinant purified Rv1768 (rRv1768) induced apoptosis of bone marrow derived macrophages (BMDMs) but showed no dose-dependent manner. Regarding macrophage activation, significant higher levels of iNOS and pro-inflammatory cytokines (like IL-6 and TNF-α) were detected in rRv1768-challenged BMDMs, whereas arginase 1 (Arg1) expression was markedly decreased. Meanwhile, MHC-II expression and antigen presentation activity of BMDMs were also enhanced by rRv1768 stimulation, leading to significantly increased IFN-γ expression of CD4+ T cells isolated from H37Rv-infected mice. It is worthy to note that Rv1768-induced IFN-γ production of peripheral blood mononuclear cells (PBMCs) and Rv1768-specific immunoglobulins was specifically observed in H37Rv-infected mice, but not BCG-infected or normal mice. Analysis of clinical blood samples further revealed that Rv1768 had a higher sensitivity and specificity (91.38 and 96.83%) for tuberculosis diagnosis than the results obtained from clinical CFP10 and ESAT6 peptides (CE)-based enzyme-linked immunospot (ELISPOT) assay. The area under ROC curve of Rv1768 was 0.9618 (95% CI: 0.919-1.000) when cutoff value set as 7 spots. In addition, Rv1768-specific IgG and IgM also exhibited moderate diagnostic performance for tuberculosis compared with CE specific antibodies. Our data suggest that Rv1768 is an antigen that strongly activates macrophages and has potential to serve as a novel ELISPOT-based TB diagnostic agent.

4-HNE Induces Apoptosis of Human Retinal Pigment Epithelial Cells by Modifying HSP70.

The role of heat shock protein 70 (HSP70) in apoptosis of human retinal pigment epithelial cells (ARPE-19) induced by 4-hydroxy-2-nonenal (4-HNE) was explored. Different concentrations of 4-HNE were used to stimulate ARPE-19 cells, and apoptosis was measured by flow cytometry. The expression of apoptotic-related proteins, HSP70, X-linked inhibitor-of-apoptosis (XIAP), Bcl-2, and Bax were quantified by Western blotting. HSP70 and XIAP overexpression plasmids, or their corresponding siRNAs were transfected into ARPE-19 cells using Lipofectamine™ 2000. Co-immunoprecipitation and Western blotting were used to detect the effect of 4-HNE on the expression of HSP70 and the binding level between 4-HNE and HSP70. The results showed that 4-HNE induced late apoptosis in ARPE-19 cells, accompanied by elevated levels of 4-HNE-modified HSP70, but it did not affect HSP70 protein expression. 4-HNE-modified HSP70 down-regulated the expression of the apoptosis inhibitory protein XIAP. Overexpression of HSP70 or XIAP inhibited 4-HNE-induced apoptosis of ARPE-19 cells. It was suggested that 4-HNE could promote XIAP degradation by modification of HSP70 to induce late apoptosis of human retinal pigment epithelial cells.

Pathological analysis of the superior mesenteric artery boundary in preoperative computed tomography of resectable pancreatic head adenocarcinoma.

The aim of the present study was to evaluate the biological and prognostic implications of the superior mesenteric artery (SMA) boundary on preoperative abdominal contrast-enhanced computed tomography (CE-CT) for resectable adenocarcinoma of the pancreatic head. A total of 121 patients treated over a 6-year period at Peking University Third Hospital (Beijing, China) were included in the present study. The pattern of the SMA boundary was investigated on preoperative CE-CT and detailed pathological analysis of the extrapancreatic plexus [the pancreatic head plexus II (PLX-II) located on the right edge of the SMA] was performed. The results revealed that the radiological SMA boundary was associated with the grade of parasympathetic neurogenesis (P=0.014) in PLX-II, and was predictive of postoperative disease-free survival (P=0.014) and liver metastasis (P=0.013). Therefore, it was proposed that extrapancreatic parasympathetic neurogenesis may account for the different patterns of the SMA boundary on preoperative abdominal CE-CT, and affect the prognosis, particularly for liver metastasis in resectable pancreatic head adenocarcinoma.

Clinicopathological features and prognosis factors for survival in elderly patients with pancreatic neuroendocrine tumor: A STROBE-compliant article.

To investigate the features and prognosis of the elderly patients with pancreatic neuroendocrine tumor (pNET).The patients diagnosed with pNETs between 2004 and 2014 were identified from the Surveillance Epidemiology and End Results database. The ethical approval was waived because the present study was analysis of the data from Surveillance Epidemiology and End Results database.A total of 4608 patients with "one primary only" histologically pNETs were confirmed and 653 were older than 75 years. Cancer-specific survival (CSS) and overall survival (OS) were examined. The elderly patients (≥75 years) have disadvantage in CSS and OS compared with younger cohort. Multivariate logistic regression revealed that the elderly patients have increased poorly differentiated composition, and decreased proportion of Black patients, receipt of surgery, married status, and number of removed lymph node. Multivariate Cox regression analysis demonstrated worse differentiation. Patients of T3-4 and M1 stage were associated with poor CSS, while patients of being female, tumor locating at pancreatic body/tail, receipt of surgery, and being married were associated with better CSS in the elderly patients. Meanwhile, patients with higher histological grade and M1 stage have poor OS, while patients with the characteristics of female, being married, tumor location at pancreatic body/tail and tumor surgery have better OS. Distant metastatic elderly patients underwent primary site surgery had better CSS and OS than the patients without surgery.The elderly patients have increased possibility of poorly differentiated tumor, and decreased proportion of Black patients, surgery of primary site, number of removed lymph node and married status. Worse differentiation and tumor metastasis were independent risk factors for both CSS and OS, while primary tumor located in body/tail of pancreas, female patients, surgery of tumor primary site, and being married were protective factors.

Extrapancreatic Neuropathy Correlates with Early Liver Metastasis in Pancreatic Head Adenocarcinoma.

BACKGROUND: Pancreatic ductal adenocarcinoma has a devastatingly poor prognosis, and most prognostic factors reflected the tumor stage more than the tumors' biology. The peripheral nerve plexus is densely distributed in the tumor micro-environment, and there are interactions between tumor cells and these nerves. Perineural invasion is an important risk factor for tumor recurrence and metastasis in pancreatic head adenocarcinoma, but the concrete types of extrapancreatic neuropathy and its role in predicting prognosis are still not clear. OBJECTIVE: To clarify the role of extrapancreatic neuropathy in the early postoperative liver metastasis and tumor-related mortality in pancreatic head adenocarcinoma and to study the mechanism of tumor recurrence and liver metastasis in pancreatic head adenocarcinoma. METHODS: We reported a retrospective study of 60 patients with resectable pancreatic head adenocarcinoma, all of whom accepted radical pancreaticoduodenectomy. Plexus pancreaticus capitalis II (PLX-II) was the representation of extrapancreatic plexus in our study, and all of these plexus had immunohistochemical staining. We defined the postoperative tumor recurrence and tumor-related mortality within 6 months as the early prognostic indicators and analyzed the pathological alterations in PLX-II among different prognosis groups. RESULTS: There were 18 patients suffering early postoperative liver metastasis; these two groups differed significantly in the average number of nerve trunks (P<0.001), the proportion of neuritis (P=0.003), the content of sympathetic nerve fibers (P=0.004) and parasympathetic nerve fibers (P<0.001) per unit area of PLX-II. There were 15 patients suffering early postoperative mortality, and there were significant differences between these two groups in the average number of nerve trunks (P<0.001), the proportion of neuritis (P=0.009), the content of sympathetic nerve fibers (P=0.023) and parasympathetic nerve fibers (P<0.001) per unit area of PLX-II. CONCLUSION: The patterns of extrapancreatic neuropathy could reflect the biological behavior of resectable pancreatic head adenocarcinoma, and the pathological features of PLX-II were closely related to early liver metastasis and mortality.