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Background: Here we describe the treatments and prognosis for metachronous metastases from gastroenteropancreatic neuroendocrine tumors (GEP-NETs) after initial R0 surgical resection at a large center in China., Methods: The clinicopathological data and survival outcomes for 108 patients (median age, 54.0 years) with metachronous hepatic metastatic GEP-NETs disease who were initially treated using R0 surgical resection between August 2003 and July 2014 were analyzed using one-way comparisons, survival analysis, and a predictive nomogram., Results: Fifty-five (50.9%) patients had pancreatic NETs and 92 (85.2%) had G2 primary tumors. For treatment of the hepatic metastases, 48 (44.4%) patients received liver-directed local treatment (metastasectomy, radiofrequency ablation, transcatheter arterial chemoembolization, etc.), 15 (13.9%) received systemic treatment (interferon, somatostatin analogs, etc.), and 45 (41.7%) received both treatments. Multivariable analyses revealed that OS was associated with hepatic tumor number (P < 0.001), treatment modality (P = 0.045), and elevated Ki-67 index between the metastatic and primary lesions (P = 0.027). The predictive nomogram C-index was 0.63., Conclusions: A higher Ki-67 index in metastases compared to primary tumor was an independent factor for poor prognosis. Local treatment was associated with prolonged survival of hepatic metastatic GEP-NET patients. Optimal treatment strategies based on clinicopathological characteristics should be developed.

Moscatilin is a bibenzyl derivative extracted from the Dendrobium aurantiacum var. denneanum, which has traditionally been used as an immunomodulatory treatment in China. The present study was designed to determine whether moscatilin is a pro‑apoptotic agent in pancreatic cancer, and to elucidate the underlying mechanisms. The apoptotic and anti‑proliferative effects of moscatilin on pancreatic cancer cells were determined in vitro using biochemical assays, such as the MTT assay, colony formation assay, Hoechst staining and DNA fragmentation assay, and in vivo using Panc‑1 pancreatic cancer xenografts. Western blotting was also conducted to evaluate the expression levels of B‑cell lymphoma 2 (Bcl2), Bcl2‑associated X protein (Bax), Bcl2 homologous antagonist killer (Bak), caspase 3, cleaved‑caspase 3, poly (ADP‑ribose) polymerase, p‑c‑Jun N‑terminal kinase (JNK)/stress‑activated protein kinases (SAPK) and JNK/SAPK in response to moscatilin. We used DCFH‑DA to detect the production of reactive oxygen species (ROS) induced by moscatilin. The present study demonstrated that moscatilin markedly inhibited pancreatic cancer cell viability and induced cell apoptosis in a concentration‑dependent manner. Conversely, moscatilin did not affect the cell viability of human umbilical vein endothelial cells at the comparable dosage. Treatment with moscatilin suppressed clonogenicity of Panc‑1 cells in a concentration‑dependent manner. Furthermore, a decrease in Bcl2 expression, and an increase in the expression levels of Bak and Bax, was detected following treatment with moscatilin, resulting in an increase in the proapoptotic/anti‑apoptotic expression ratio (Bax/Bcl2) in Panc‑1 cells. Moscatilin also induced activation of the caspase‑dependent mitochondrial apoptotic pathway. In addition, moscatilin enhanced cellular ROS production and induced activation of JNKSAPK signaling pathway. Conversely, pretreatment with the ROS scavenger N‑acetylcysteine or the JNK/SAPK‑specific inhibitor SP600125 prevented moscatilin‑mediated reductions in cell viability. Furthermore, moscatilin inhibited tumor growth in nude mice bearing Panc‑1 cells, without apparent toxicity. In conclusion, these results demonstrated that moscatilin may induce pancreatic cell apoptosis, and therefore may be considered a potential therapeutic agent for the treatment of pancreatic cancer.

Purpose: We aimed to explore the potential value of the whole tumor apparent diffusion coefficient (ADC) for discriminating between benign and malignant intraductal papillary mucinous neoplasms (IPMNs) of the pancreas., Methods: Forty-two patients underwent 1.5 T magnetic resonance imaging that included diffusion-weighted imaging (DWI, b=0.500 s/mm2). The mean, minimum, and maximum ADC values were measured for the whole tumor. The differences between benign and malignant IPMNs were calculated for the mean ADC, ADC-min, and ADC-max values. Receiver operating characteristics (ROC) analysis was conducted to evaluate their potential diagnostic performance., Results: Fifteen of 25 benign IPMNs demonstrated low or iso-signal intensity on DWI with a b value of 500 s/mm2 compared with normal pancreatic parenchyma, whereas all malignant IPMNs demonstrated high signal intensity. The mean value of ADC was significantly higher in benign IPMNs compared with malignant IPMNs (3.39×10-3 mm2/s vs. 2.39×10-3 mm2/s, P < 0.001), with an area under the ROC curve (AUC) of 0.92 (95% confidence interval [CI], 0.79-0.98). The ADC-min value of malignant IPMNs was also significantly lower than that of benign IPMNs (1.24×10-3 mm2/s vs. 2.58×10-3 mm2/s, P < 0.001), with an AUC of 0.94 (95% CI, 0.82-0.99). No marked difference was found between benign and malignant IPMNs for the ADC-max value (3.89×10-3 mm2/s vs. 3.78×10-3 mm2/s, P = 0.299)., Conclusion: Lower mean and minimum ADC values of the whole tumor might be potential predictors of malignant IPMNs of the pancreas.

Objectives: To investigate the antitumor activity of nanoparticle albumin-bound paclitaxel (nab-paclitaxel) plus S-1 in patient-derived pancreatic cancer xenograft mouse models and to explore biomarkers that could predict drug efficacy., Methods: Ten patient-derived xenograft models were established. The third-generation tumor-bearing mice were randomized into 4 treatment groups: (1) control; (2) S-1; (3) nab-paclitaxel; (4) S-1 plus nab-paclitaxel. Resected tumors were tested by immunohistochemistry for the expression of thymidylate synthase, orotate phosphoribosyltransferase (OPRT), dihydropyrimidine dehydrogenase (DPD), secreted protein that is acidic and rich in cysteine, human epidermal growth factor receptor 2 (HER2), collagen-1, and CD31., Results: Tumor growth inhibition of the S-1 group, nab-paclitaxel group, and combination group was 69.52%, 86.63%, 103.56%, respectively (P < 0.05). The efficacy of S-1 is better in thymidylate synthase-negative, OPRT-positive, and DPD-negative tumors. The efficacy of nab-paclitaxel is better in HER2-positive tumors. Collagen-1 was decreased and CD31 was increased in tumors treated with nab-paclitaxel and S-1 plus nab-paclitaxel compared with control or S-1., Conclusions: This preclinical study showed that S-1 plus nab-paclitaxel exerted significantly better antitumor activity than S-1 or nab-paclitaxel alone. Thymidylate synthase, OPRT, and DPD were possibly biomarkers of S-1 and HER2 of nab-paclitaxel.

Objective: To investigate the relationship between pancreatic cancer (PC) and diabetes mellitus., Methods: All PC patients diagnosed and treated at Zhongshan hospital from January 1991 to December 2007 were retrospectively analyzed. During this period, 770 non-digestive tract, non-neoplastic and non-hormone-related patients matched for sex and age were collected as controls. The incidence of diabetes mellitus between the two groups was compared., Results: Between the PC group and the control group, sex and age of the patients were well matched. The incidence of diabetes mellitus was 34.63% in the PC group and 8.83% in the control group (P < 0.001, RR = 5.19). In the PC group there was no correlation between age, sex, site of the cancer, tumor differentiation, lymph node metastasis, TNM staging and the incidence of diabetes mellitus. In this group with diabetes, 74.56% experienced onset within two years of cancer diagnosis. Of the control patients, 57.35% had had diabetes for under 2 years (P = 0.009, RR = 2.18). In the PC group with diabetes, 5.9% had had diabetes for more than 10 years while compared with 8.8% of the controls (P = 0.42)., Conclusion: Whether diabetes mellitus is a result of or a risk factor for PC is still unclear. The incidence of diabetes mellitus is much higher in the PC patients. The onset of diabetes mellitus in adults might be an alerting factor that could lead to an early diagnosis of pancreatic cancer.

Objective: To explore the diagnosis, clinical manifestation, treatment, and prognosis of intraductal papillary mucinous neoplasms (IPMNs) of pancreas., Methods: The clinical data of 38 patients with IPMNs, 23 males and 15 females, aged 64.1 +/- 10.7 (41 - 81), were analyzed respectively., Results: The main symptoms included abdominal pain and jaundice. Pancreaticoduodenectomy was performed on 32 patients, total pancreatectomy on 1 patient, distal pancreatectomy on 3 patients; and pancreatic biopsy on 2 patients. One patient died during the peri-operational period. Pathology showed 15 cases of main-duct type, 14 cases of branch-duct type, 1 case of mixed type, and 8 cases being un-differentiated, all with dilatation of pancreatic duct at different degrees 4.6 mm in diameter on average. There were 30 cases of invasive IPMNs, with significantly higher level of carbohydrate antigen 19-9 (CA19-9), and 8 non-invasive. The median survival time was 18.5 months in general. In the invasive IPMN group the general median survival time was 16.1 months, and the 1, 2, and 5-year survival times were 54%, 31%, and 21% respectively; and in the non-invasive IPMN group the median survival time was 24.3 months, and the 1, 2, and 5-year survival times were 58% and 38% respectively; without significant differences in the survival times between these 2 groups. TMN staging showed 6 cases of stage 0, 15 cases of stage I, 9 cases of stage II, and 4 cases of stage III among the 34 patients of malignant IPMNs. The median survival times of the patients of the stages 0, I, II, and III were 31.3, 27, 9.1, and 8.9 months respectively with significant differences among them (P = 0.0124)., Conclusion: IPMN of pancreas has no specific clinical manifestation. Dilatation of pancreatic duct is a manifestation in imaging examination characteristic of IPMN. The serum CA19-9 level is significantly higher in the patients with invasive IPMN. There are significant differences in survival rate among different groups according to TMN staging.