efeng Xu

The association between BMP4 gene polymorphism and its serum level with the incidence of LVH in hypertensive patients.

BackgroundBone morphogenic proteins 4 (BMP4) is associated with cardiac remodeling under different conditions. However, the role of BMP4 and its gene polymorphism in the incidence of left ventricular hypertrophy (LVH) in hypertensive patients remains unknown.MethodsA total of 1265 patients diagnosed with essential hypertension (EH) were recruited. Patients were assigned to LVH+ (n = 420) and LVH- (n = 845) groups. serum BMP4 level was measured and two single nucleotide polymorphism (SNPs) polymorphisms, 6007C > T and -5826G > A of BMP4 gene were genotyped. We also inhibited the BMP4 by small interfering RNA (siRNA). The effect of BMP4 on the hypertrophic response in Human Cardiomyocytes AC16 cells was studied.ResultsWe found that the 6007C > T polymorphism of the BMP4 gene and the serum BMP4 level were significantly associated with the risk to develop LVH. With TT as reference, multivariate logistic regression analysis showed the 6007CC genotype carriers had a higher susceptibility to LVH incidence (adjusted OR = 2.65, 95% CI: 1.63-4.31, adjusted P < 0.001). Our in vitro study shows that the BMP4 inhibition in cardiomyocyte by si-RNA technique significantly decreased the Ang II induced cardiomyocyte size and protein content per cell, indicating the importance of BMP4 in the cardiomyocyte hypertrophy.ConclusionCollectively, our data suggest that both the 6007C > T of the BMP4 gene and the serum BMP4 level may be used as potential marker for LVH incidence among the EH patients.

Survival prediction in pancreatic cancer patients with no distant metastasis: a large-scale population-based estimate

AIM To identify the risk factors for overall survival (OS) of pancreatic ductal adenocarcinoma patients with no distant metastasis, and formulate a novel nomogram for prognostic prediction. PATIENTS & METHODS Data were obtained from Surveillance, Epidemiology, and End Results database of pancreatic ductal adenocarcinoma patients with no distant metastasis as the primary cohort, and 127 patients at our institution were enrolled as the validation cohort. The prognostic nomogram integrating all independent risk factors for predicting OS was established to achieve superior discriminatory ability. RESULTS The constructed nomogram showed excellent performance and superior predictive accuracy for OS according to the concordance index and calibration curve. CONCLUSION One more advanced and accurate predictive model will be obtained to assist in risk stratification via the constructed nomogram.

Prognostic value of histological subtype in intraductal papillary mucinous neoplasm of the pancreas: A retrospective analysis of outcome from one single center

Abstract We sought to retrospectively analyze the outcomes of patients with intraductal papillary mucinous neoplasm (IPMN) at our pancreatic surgery center, and to evaluate the prognostic value of histological subtype. The clinical data of 121 IPMNs treated in our center between 2005 and 2014 were retrospectively analyzed. Pathological slides were thoroughly reviewed by 2 specialized pathologists. Of the 121 patients, 48, 57, and 16 had main-duct, branch-duct, and mixed type IPMNs, respectively. Forty-one patients had invasive IPMNs. Histological subtypes consisted of 35 intestinal (28.9%), 56 gastric (46.3%), 29 pancreatobiliary (24.0%), and 1 oncocytic type (0.8%). Histological subtype was associated with radiological type, T stage, and degree of dysplasia (P < .05). No significant difference in overall survival was observed among the 4 histological subtypes, regardless of whether we considered all IPMNs (P = .106), or invasive IPMNs only (P = .828). However, the overall survival was associated with radiological type, T stage, degree of dysplasia, lymph-node status, and nerve invasion. For invasive IPMNs, the overall survival was associated with nerve invasion and lymph-node status; however, the association between nerve invasion and overall survival lost statistical significance after multivariate analysis. Histological subtype had limited prognostic value in patients with IPMNs, and the main prognostic factor for patients with invasive IPMNs was the lymph-node status.

Alkaline Phosphatase-To-Albumin Ratio as a Prognostic Indicator in Pancreatic Ductal Adenocarcinoma after Curative Resection

Background: The prognosis of pancreatic ductal adenocarcinoma (PDAC) remains poor and the models for survival prediction in PDAC patients after curative resection are still limited. Preoperative alkaline phosphatase-to-albumin ratio (APAR), an original inflammation-based score, has been established to analyze the prognostic significance in PDAC. Therefore, in this study, we aim to formulate a valuable prognostic nomogram for PDAC following curative resection. Methods: A total of 354 patients with PDAC undergoing curative resection were retrospectively enrolled in this study. The prognostic value of APAR was analyzed in primary cohort containing 220 randomly selected PDAC patients with curative resection and prognostic nomogram incorporating APAR into the American Joint Commission on Cancer (AJCC) 8th edition was established to obtain superior discriminatory abilities. The predictive performance of APAR was further validated in another independent cohort of 134 PDAC patients. Results: Patients with higher serum APAR level were probable to sustain poorer overall survival (OS). Significant positive correlations were found between APAR and tumor site, and several serum biochemical indexes, such as aspartate aminotransferase (AST), alanine aminotransferase (ALT), etc. The results of multivariate analysis showed, APAR was also identified as an independent prognostic indicator for OS in both primary and validation cohorts (P=0.004, P=0.038, respectively). Compared with the AJCC 8th edition, the nomogram consisting of APAR, pathological differentiation and the TNM staging system of AJCC 8th edition showed superior predictive accuracy for OS. All these results were further verified in the validation cohort. Conclusions: APAR can be considered as a novel independent prognostic biomarker for PDAC following curative resection. One more accurate and advanced predictive model will be achieved via the incorporation of APAR into nomogram.

An analysis of clinico-pathologic features of intraductal papillary mucinous neoplasm of the pancreas.

The natural history and clinical manifestation of resected intraductal papillary mucinous neoplasm (IPMN) of the pancreas were elucidated, and based on this, a retrospective pancreatic database was reviewed to identify patients with IPMN who were surgically managed in our department from 1999 to June 2006. Pathologic rereview of each case was performed, and the clinico-pathologic features were examined. Student’s T test and χ2 analysis were used to identify factors associated with malignancy. Fifty-one patients were identified. There were 33 males and 18 females. One patient’s pancreas was unresectable, two patients underwent a total pancreatectomy, 42 patients had a pancreatecoduodenectomy and five patients had distal pancreatectomy. Main-duct type carcinoma was identified in 24 patients; branch-duct type in 15 patients, and mixed type in 12 patients. Invasive carcinoma was present in 35 patients. Weight loss and jaundice occurred more commonly in the invasive group. The average serum CA19-9 level was significantly higher in the invasive group (1542μ vs 94.5μ). The average diameter of the pancreatic duct was also wider in the invasive group (8.7 mm vs 4.3 mm). Significant predictors of malignant IPMNs included weight loss, jaundice, a high level of serum CA19-9, a large pancreatic duct and main-duct type carcinoma.

The latest exploration of staging and prognostic classification for pancreatic neuroendocrine tumors: a large population-based study

Background: A modified European Neuroendocrine Tumor Society (mENETS) staging system has been confirmed to be more suitable for pancreatic neuroendocrine tumors (pNETs) when compared to the American Joint Committee on Cancer (AJCC) or the European Neuroendocrine Tumor Society (ENETS) systems in the last few years. However, the importance of N stage has been recently published with several significant updates. Methods: SEER registry (n = 2,209) was used to evaluate the application of the AJCC 7th staging system, ENETS staging system, mENETS staging system and reformed ENETS (rENETS) staging system in this study. Results: For the ENETS staging system, patients with stage I disease had a similar prognosis to patients with stage II disease (P=0.154), and patients with stage IIIA and stage IIIB diseases showed adverse prognostic potential. The proportion of patients with stage III diseases using AJCC 7th staging system was extremely lower than those with mENETS staging system or rENETS staging system (3.6%, 23.0% and 23.7%, respectively). Furthermore, the hazard ratio of death for patients with stage II or III disease using rENETS staging system was slightly higher than that of mENETS staging system. Besides, survival curves were better separated by rENETS staging system. A prognostic nomogram for overall survival (OS) was formulated to obtain superior discriminatory abilities. Conclusions: The rENETS staging system has superior distribution in proportion than the AJCC 7th, ENETS or mENETS staging system, and one more accurate and advanced predictive model will be achieved via the incorporation to be adopted in clinical practice.

Clinicopathological Characteristics of the primary and metastatic Hepatic Neuroendocrine Tumors and the relevant Prognosis-Related Factors: A Retrospective Study of 81 Cases in a Single Chinese Center

Aims: We aim to describe the clinicopathological characteristics of hepatic neuroendocrine tumors (HNETs) and evaluate the relevant prognosis-related factors. Methods: The clinical data of 81 consecutive patients with primary or metastatic HNETs from March 2000 to July 2014 were retrospectively analyzed. Results: The mean (SD) age was 59.68 (11.64) years, 69.15% were men. The percentages of Grade G1, G2 and G3 tumors were 4.94%, 25.93% and 69.13%, respectively. Thirty-five cases were primary HNETs. Primary HNETs were more common in patients with larger tumors, lymph nodes invasions, tumor necrosis and portal vein tumor thrombus. The 1-, 3-, and 5-year overall survival rate were 88.89%, 32.10%, and 8.64%, separately. The relapse rate was 81.48% (66/81) and the mean (SD) relapse time was 18.79 (10.99) months. Reduced survival rate was associated with lymph node metastases (P=0.034), tumor necrosis (P=0.048), hard texture of tumor character (P=0.001), multifocality of tumor numbers (P=0.043), and the immunohistochemical expression of NSE (P=0.000) and Syn (P=0.037). Patients with metastatic HNETs were demonstrated with a more decreased period of Progression-free Survival (PFS) and Overall survival (OS) than their primary HNETs counterparts (P<0.05). Conclusion: Primary HNETs cohort patients were more common with aggressive clinical presentation. The hard texture of tumor character, multifocality of tumor numbers, and the immunohistochemical expression of NSE and Syn were independent predictive factors. Patients who were pathologically diagnosed as the primary HNETs seemed to achieve a long-term survival.

Chk1 inhibitor SCH 900776 enhances the antitumor activity of MLN4924 on pancreatic cancer

ABSTRACT MLN4924 inhibits the cullin-RING ligases mediated ubiquitin-proteasome system, and has showed antitumor activities in preclinical studies, but its effects and mechanisms on pancreatic cancer (PC) remains elusive. We found that MLN4924 inhibited the proliferation and clonogenicity of PC cells, caused DNA damage, particularly double-strand breaks, and leaded to Chk1 activation and cell-cycle arrest. Chk1 inhibitor SCH 900776 alone exhibited minimal cytotoxicity, and caused no DNA damage on PC cells. But in the combination therapy, SCH 900776 enhanced the cytotoxicity and DNA damage caused by MLN4924, likely by abrogating G2/M arrest and promoting DNA re-replication. In vivo study on a xenograft PC mouse model also showed that SCH 900776 increased the efficacy of MLN4924. We also evaluated the level of NEDD8-activating enzyme (NAE), the direct target of MLN4924, and found that NAE level was elevated in PC tissues compared with normal pancreas, but was irrelevant with prognosis. Our findings provide the preclinical evidence and the rationale of the combination therapy of MLN4924 with SCH 900776 or other Chk1 inhibitors to treat PC.

Long-term survival following total pancreatectomy and superior mesenteric-portal vein resection for pancreatic ductal adenocarcinoma: A case report.

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer with few therapeutic options. At present, surgical resection remains the only potential curative treatment for PDAC. However, only 15–20% of patients with PDAC are eligible for lesion resection. Total pancreatectomy (TP) and superior mesenteric-portal vein resection (SMPVR) may increase the rate of resection of PDCA, but the effect of this approach on improving long-term patient outcomes remains controversial. The present study investigated a case of PDAC in the pancreatic neck of a male patient. The patient underwent a TP, combined with SMPVR, for a margin-negative resection. Following an uneventful post-operative recovery, the patient received adjuvant chemoradiotherapy. The patient is currently alive at six years post-surgery, with a high quality of life. Given the clinical outcome of this patient, TP combined with SMPVR may provide PDAC patients with an opportunity for long-term survival. Therefore, patients with PDAC that is believed to be unresectable based on pre-operative assessment, may benefit from TP and SMPVR.