Biodegradable Nanoprodrugs: "Delivering" ROS to Cancer Cells for Molecular Dynamic Therapy.

Biodegradable nanoprodrugs, inheriting the antitumor effects of chemotherapy drugs and overcoming the inevitable drawback of side effects on normal tissues, hold promise as next-generation cancer therapy candidates. Biodegradable nanoprodrugs of transferrin-modified MgO2 nanosheets are developed to selectively deliver reactive oxygen species to cancer cells for molecular dynamic therapy strategy. The nanosheets favor the acidic and low catalase activity tumor microenvironment to react with proton and release nontoxic Mg2+ . This reaction simultaneously produces abundant H2 O2 to induce cell death and damage the structure of transferrin to release Fe3+ , which will react with H2 O2 to produce highly toxic ·OH to kill tumor cells.

Moscatilin induces apoptosis of pancreatic cancer cells via reactive oxygen species and the JNK/SAPK pathway.

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 pro­apoptotic agent in pancreatic cancer, and to elucidate the underlying mechanisms. The apoptotic and anti­proliferative 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 Panc­1 pancreatic cancer xenografts. Western blotting was also conducted to evaluate the expression levels of B­cell lymphoma 2 (Bcl2), Bcl2­associated X protein (Bax), Bcl2 homologous antagonist killer (Bak), caspase 3, cleaved­caspase 3, poly (ADP­ribose) polymerase, p­c­Jun N­terminal kinase (JNK)/stress­activated protein kinases (SAPK) and JNK/SAPK in response to moscatilin. We used DCFH­DA 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 concentration­dependent 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 Panc­1 cells in a concentration­dependent 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/anti­apoptotic expression ratio (Bax/Bcl2) in Panc­1 cells. Moscatilin also induced activation of the caspase­dependent mitochondrial apoptotic pathway. In addition, moscatilin enhanced cellular ROS production and induced activation of JNKSAPK signaling pathway. Conversely, pretreatment with the ROS scavenger N­acetylcysteine or the JNK/SAPK­specific inhibitor SP600125 prevented moscatilin­mediated reductions in cell viability. Furthermore, moscatilin inhibited tumor growth in nude mice bearing Panc­1 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.

SN38 increases IL-8 expression through the MAPK pathways in HCT8 cells.

The overexpression of interleukin-8 (IL-8) is closely associated with poor tumor differentiation, metastasis and tumor progression. This study aimed to examine the effects and mechanisms of action of SN38 (a metabolite of the camptothecin derivative, CPT-11) on IL-8 expression in HCT8 cells, using ELISA, CCK-8 and western blot analysis. Among jatrorrhizine, evodiamine, 5-fluorouracil and SN38, SN38 was found to inhibit the proliferation of HCT8 cells in a dose-dependent manner, but to increase IL-8 secretion from HCT8 cells. Of the other agents, evodiamine was found to inhibit both IL-8 secretion and cell proliferation, and jatrorrhizine was found to increase IL-8 secretion without any obvious inhibitory effect on cell proliferation. Further experiments revealed that the increased activation of p38 mitogen-activated protein kinase (MAPK), extracellular signal-regulated kinase (ERK)1/2 and c-Jun N-terminal kinase (JNK) by SN38 contributed to the decreased cell proliferation and to the overexpression of IL-8 induced by SN38. Our results suggested that the MAPK pathways are activated by SN38, resulting in the upregulation of IL-8 expression and in the inhibition of cell proliferation in an IL-8-independent manner. Thus, the potential benefit of the use of a combination of camptothecin-11 with other chemical drugs with inhibitory effects on IL-8 expression, should be paid more attention in treating colon cancer.

ITRAQ-based quantitative proteomics reveals apolipoprotein A-I and transferrin as potential serum markers in CA19-9 negative pancreatic ductal adenocarcinoma.

Currently the diagnosis of pancreatic ductal adenocarcinoma (PDAC) relies on CA19-9 and radiological means, whereas some patients do not have elevated levels of CA19-9 secondary to pancreatic cancer. The purpose of this study was to identify potential serum biomarkers for CA19-9 negative PDAC.A total of 114 serum samples were collected from 3 groups: CA19-9 negative PDAC patients (n = 34), CA19-9 positive PDAC patients (n = 44), and healthy volunteers (n = 36), whereas the first 12 samples from each group were used for isobaric tags for relative and absolute quantitation (iTRAQ) analysis. Thereafter, candidate biomarkers were selected for validation by enzyme-linked immunosorbent assay (ELISA) with the rest specimens.Using the iTRAQ approach, a total of 5 proteins were identified as significantly different between CA19-9 negative PDAC patients and healthy subjects according to our defined criteria. Apolipoprotein A-I (APOA-I) and transferrin (TF) were selected to validate the proteomic results by ELISA in a further 78 serum specimens. It revealed that TF significantly correlated with the degree of histological differentiation (P = 0.042), and univariate and multivariate analyses indicated that TF is an independent prognostic factor for survival (hazard ratio, 0.302; 95% confidence interval, 0.118-0.774; P = 0.013) of patients with PDAC after curative surgery.ITRAQ-based quantitative proteomics revealed that APOA-I and TF may be potential CA19-9 negative PDAC serum markers.

Increased expression of αTubulin is associated with poor prognosis in patients with pancreatic cancer after surgical resection.

BACKGROUND: αTubulin, the essential orchestrator of cytoskeletal protein polymers, critical for cell growth and division, motility, signaling development and maintenance of cell shape, plays vital roles in the oncogenesis and progression of various types of cancer, but its role in prognosis of pancreatic cancer patients remains unknown. The aim of this study was to investigate its prognostic value in patients with pancreatic cancer after surgical resection. RESULTS: αTubulin expression in pancreatic cancer was significantly associated with N classification (p = 0.013) and TNM stage (p = 0.025). Increased expression of αTubulin in tumoral tissue was associated with decreased overall survival rate (p = 0.002). Multivariate Cox regression analysis suggested that αTubulin expression was an independent prognostic indicator for pancreatic cancer except for T and N classification (p = 0.002). Using multivariate analysis, αTubulin expression, CA19-9, and N classification were selected to generate the nomogram to predict the 1-year and 3-year overall survival. The c-index of this model was 0.692. The calibration curve for probability of survival showed good agreement between prediction by nomogram and actual observation. METHODS: αTubulin expression was evaluated by tissue microarrays from 124 pancreatic cancer patients and statistically assessed for correlations with the clinical profiles and the prognosis of the patients with pancreatic cancer. The prognostic nomogram was designed to predict 1-year and 3-year overall survival probability. CONCLUSIONS: αTubulin expression might be an independent prognostic factor for pancreatic cancer after surgical resection and could potentially be a high-priority therapeutic target. Incorporating αTubulin expression into CA19-9 and N classification can provide a good prognostic model.

Value of apparent diffusion coefficient for predicting malignancy of intraductal papillary mucinous neoplasms of the pancreas.

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.

Nab-Paclitaxel Plus S-1 Shows Increased Antitumor Activity in Patient-Derived Pancreatic Cancer Xenograft Mouse Models.

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.

Resection is an effective treatment for recurrent follicular dendritic cell sarcoma from retroperitoneum: unusual presentation of a rare tumor.

Retroperitoneum follicular dendritic cell sarcoma (FDCS) is an extremely rare neoplasm. The treatment of this disease is not clear. A 49-year-old Chinese female who had been found a 4.4×4 cm retroperitoneum mass by routine physical examination was received radical resection. Pathology revealed an inflammatory pseudotumor-like follicular dendritic cell tumor. After five years follow-up, a new nodule was noted on the tail of pancreas by routine CT evaluation. Re-resection was performed and pathological examination found a spindle-cell tumor with a great quantity of froth histiocytes. Immunohistochemical stains were positive for CD35 and CD21 which suggested it was a recurrent FDCS. Retroperitoneum FDCS is a very rare tumor. Surgical resection may be the first choice for this disease, even for recurrent tumor, if feasible. A relatively good prognosis often is achieved when compared with other malignancy.

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.

iTRAQ-based quantitative proteomics reveals myoferlin as a novel prognostic predictor in pancreatic adenocarcinoma.

Histological differentiation is a major pathological parameter associated with poor prognosis in patients with pancreatic adenocarcinoma (PAC) and the molecular signature underlying PAC differentiation may involve key proteins potentially affecting the malignant characters of PAC. We aimed to identify the proteins which could be implicated in PAC prognosis. We used isobaric tags for relative and absolute quantitation (iTRAQ) coupled with two-dimensional liquid chromatography-tandem mass spectrometry to compare protein expression in PAC tissues with different degrees of histological differentiation. A total of 1623 proteins were repeatedly identified by performing the iTRAQ-based experiments twice. Of these, 15 proteins were differentially expressed according to our defined criteria. Myoferlin (MYOF) was selected to validate the proteomic results by western blotting. Immunohistochemistry in a further 154 PAC cases revealed that myoferlin significantly correlated with the degree of histological differentiation (P=0.004), and univariate and multivariate analyses indicated that MYOF is an independent prognostic factor for survival (hazard ratio, 1.540; 95% confidence interval, 1.061-2.234; P=0.023) of patients with PAC after curative surgery. RNA interference-mediated knockdown of MYOF alleviated malignant phenotypes of both primary and metastatic PAC cell lines in vitro and in vivo. Thus, ITRAQ-based quantitative proteomics revealed the prognostic value of MYOF in PAC. BIOLOGICAL SIGNIFICANCE: Our results provide the possibility of novel strategies for pancreatic adenocarcinoma management.

Clinical strategies for differentiating autoimmune pancreatitis from pancreatic malignancy to avoid unnecessary surgical resection.

OBJECTIVE: The study aimed to determine a practical strategy for differentiating between autoimmune pancreatitis (AIP) and pancreatic malignancy in order to avoid unnecessary surgical resection. METHODS: Altogether, 19 patients with AIP or other pancreatic diseases underwent routine examinations including liver function test and carbohydrate antigen 19-9, computed tomography and/or magnetic resonance imaging. Serum immunoglobulin G (IgG) and/or IgG4 was determined in patients with clinically suspected or pathologically proven AIP. Patients with suspected AIP either received diagnostic steroid therapy or laparotomy (if malignant tumors could not be excluded). Surgery was not performed in patients with a definite diagnosis of AIP by fast intraoperative frozen biopsy. Those with confirmed AIP received steroid treatment. RESULTS: In total, 15 cases were finally confirmed as AIP with eight diagnosed preoperatively, five confirmed by surgical pathology (preoperatively misdiagnosed) and two by intraoperative biopsy. Of these 15 patients with AIP and one without AIP, 14 had elevated serum γ-globulin levels. It was proven by subsequent antibody tests that serum IgG or IgG4 were simultaneously increased. CONCLUSIONS: Elevated serum γ-globulin level can be used as a preoperative sentinel indicator for differentiating between IgG4-related AIP and pancreatic malignancy. Serum IgG or IgG4 tests should be further performed in those with elevated serum γ-globulin level, which helps to identify AIP in order to avoid unnecessary operation.

Identification of proteins implicated in the development of pancreatic cancer-associated diabetes mellitus by iTRAQ-based quantitative proteomics.

Studies have revealed that pancreatic cancer (PC) may lead to diabetes mellitus (DM). We aimed to identify the proteins implicated in the development of PC-associated DM in PC tissues with DM. We used isobaric tags for relative and absolute quantitation (iTRAQ) coupled with two-dimensional liquid chromatography-tandem mass spectrometry to compare protein expression in PC tissues with DM with that in PC tissues without DM and in adjacent nontumor tissues with or without DM. A total of 80 surgically resected fresh tissues from 40 PC patients were included to identify differential protein expression. Western blotting and immunohistochemistry were then applied to evaluate the differential expression of selected proteins. A total of 1611 proteins were repeatedly identified and quantified by performing the iTRAQ-based experiments twice. Of these, 23 proteins were differentially expressed according to our defined criteria (12 upregulated and 11 downregulated). The S100 calcium binding protein A9 and aldehyde dehydrogenase 2 family were selected to validate the proteomic results by western blotting and immunohistochemistry. The identification of key proteins implicated in the development of PC-associated DM could serve as a foundation to better understand and further explore the etiology and pathogenesis of PC-associated DM. BIOLOGICAL SIGNIFICANCE: The identification of key proteins implicated in the development of PC-associated DM could serve as a foundation to better understand and further explore the etiology and pathogenesis of PC-associated DM.

Lipocalin-2 is associated with a good prognosis and reversing epithelial-to-mesenchymal transition in pancreatic cancer.

BACKGROUND: Lipocalin-2 is a multifaceted modulator in cancer progression. Its clinical significance is not clear in pancreatic cancer. The purpose of this study was to investigate whether lipocalin-2 is associated with good prognosis by reversing epithelial-to-mesenchymal transition (EMT) in pancreatic cancer. METHODS: Lipocalin-2, E-cadherin, or vimentin expression was detected in 60 pancreatic adenocarcinoma specimens. Correlations between lipocalin-2 expression and EMT, the clinicopathologic characteristics, and prognosis were investigated. Whether pancreatic cancer cells' migration and invasion (some characteristics of EMT) were affected by lipocalin-2 was also explored. RESULTS: High lipocalin-2 expression was significantly associated with a good prognosis in pancreatic cancer (p < 0.05). Overexpression of lipocalin-2 correlated with a lower extent of EMT (p < 0.05), increased E-cadherin expression (p < 0.05), decreased vimentin expression (p < 0.05), and reduced cancer cell migration and invasion in pancreatic cancer. CONCLUSIONS: Lipocalin-2 may be considered an epithelial inducer, which may reverse EMT and predict a good prognosis in pancreatic cancer.

Decision making for pancreatic resection in patients with intraductal papillary mucinous neoplasms.

AIM: To identify a practical approach for preoperative decision-making in patients with intraductal papillary mucinous neoplasms (IPMNs) of the pancreas. METHODS: Between March 1999 and November 2006, the clinical characteristics, pathological data and computed tomography/magnetic resonance imaging (CT/MRI) of 54 IPMNs cases were retrieved and analyzed. The relationships between the above data and decision-making for pancreatic resection were analyzed using SPSS 13.0 software. Univariate analysis of risk factors for malignant or invasive IPMNs was performed with regard to the following variables: carcinoembryonic antigen, carbohydrate antigen 19-9 (CA19-9) and the characteristics from CT/MRI images. Receiver operating characteristic (ROC) curve analysis for pancreatic resection was performed using significant factors from the univariate analysis. RESULTS: CT/MRI images, including main and mixed duct IPMNs, tumor size > 30 mm or a solid component appearance in the lesion, and preoperative serum CA19-9 > 37 U/mL had good predictive value for determining pancreatic resection (P < 0.05), but with limitations. Combining the above factors (CT/MRI images and CA19-9) improved the accuracy and sensitivity for determining pancreatic resection in IPMNs. Using ROC analysis, the area under the curve reached 0.893 (P < 0.01, 95%CI: 0.763-1.023), with a sensitivity, specificity, positive predictive value and negative predictive value of 95.2%, 83.3%, 95.2% and 83.3%, respectively. CONCLUSION: Combining preoperative CT/MRI images and CA19-9 level may provide useful information for surgical decision-making in IPMNs.

Combined serum CA19-9 and miR-27a-3p in peripheral blood mononuclear cells to diagnose pancreatic cancer.

MicroRNAs are potentially very useful biomarkers in the diagnosis of cancer. We sought to identify specific microRNAs in peripheral blood mononuclear cells (PBMCs) whose levels might facilitate diagnosis of pancreatic cancer. We investigated PBMC microRNA expression in three independent cohorts [healthy, benign pancreatic/peripancreatic diseases (BPD), and pancreatic cancer], comprising a total of 352 participants. First, we used sequencing technology to identify differentially expressed microRNAs in PBMC of pancreatic cancer, BPD, and healthy controls (n = 20 in each group). Then the selected microRNAs were analyzed using the quantitative reverse transcriptase PCR assays in the remaining 292 samples. The predictive value of the microRNAs was evaluated by logistic regression models and the receiver operating characteristic curve (AUC). We found that miR-27a-3p level in PBMCs could discriminate pancreatic cancer from BPD with a sensitivity of 82.2% and specificity of 76.7% (AUC = 0.840; 95% CI, 0.787-0.885%). Combination of PBMC miR-27a-3p and serum CA19-9 levels provided a higher diagnostic accuracy with a sensitivity of 85.3% and specificity of 81.6% (AUC = 0.886; 95% CI, 0.837-0.923%). The satisfactory diagnostic performance of the panel persisted regardless of disease status (AUCs for tumor-node-metastasis stages I-III were 0.881, 0.884, and 0.893, respectively). PBMC miR-27a-3p level represents a potential marker for pancreatic cancer screening. A panel combining serum CA19-9 and PBMC miR-27a-3p level could have considerable clinical value in diagnosing pancreatic cancer.

Treatment of pancreatic cancer using an oncolytic virus harboring the lipocalin-2 gene.

BACKGROUND: The 5-year survival rate for patients with pancreatic cancer is <5%, and it is always resistant to the current chemoradiotherapy. Therefore, new, effective agents for the treatment of pancreatic cancer are urgently needed. The promising strategy of cancer-targeting gene virotherapy (CTGVT) has demonstrated great anticancer potential. The objective of the current study was to determine whether 1 CTGVT approach, oncolytic virus (OV)-harboring lipocalin-2, is capable of treating pancreatic cancer. METHODS: Tissue microarrays were constructed to detect the expression of lipocalin-2 in 60 specimens of pancreatic adenocarcinoma. The clinical significance of lipocalin-2 was investigated in an analysis of correlations between lipocalin-2 expression and matched clinical characteristics. A lipocalin-2-expressing OV, ZD55-lipocalin-2, was constructed by deleting the adenoviral protein E1B55kD. The antitumor efficacy and mechanisms of the OV were investigated in pancreatic cancer cells with v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations in vitro and in vivo. RESULTS: Lipocalin-2 expression was correlated with a good prognosis in patients with pancreatic adenocarcinoma. ZD55-lipocalin-2 dramatically inhibited the growth of pancreatic cancer in vitro and in vivo by inducing cytolysis and caspase-dependent apoptosis. CONCLUSIONS: Higher lipocalin-2 expression predicted a better prognosis in patients with pancreatic cancer. The results indicated that ZD55-lipocalin-2, which specifically expressed higher levels of lipocalin-2 in tumor cells, may serve as a potent anticancer drug for pancreatic cancer therapy, especially for patients who have pancreatic adenocarcinoma with KRAS mutations.

Small solid tumors (< or = 2 cm) of the pancreas: relative accuracy and differentiation of CT and MR imaging.

BACKGROUND/AIMS: To determine the relative accuracy of CT and MRI in characterization of solid pancreatic masses (< or = 2cm) and useful imaging appearance for differentiating small pancreatic duct adenocarcinoma (PDAC) from other small solid pancreatic neoplasms. METHODOLOGY: CT and MRI scans of 46 patients with evidence of small pancreatic solid tumor were retrospectively evaluated, who underwent CT (n=30), MRI (n=4), or both (n=12). Two gastrointestinal radiologists independently recorded specific morphological features of tumors and the most likely diagnosis. RESULTS: With respect to specific histopathological characterization, CT and MRI were equally accurate. The mean number of correct diagnoses made by the two reviewers was 37.5 (88.4%) of 42 cases for CT compared to 12 (75%) of 16 cases for MRI (p=0.388). Location in the pancreatic head (p=0.000), presence of dilatation of MPD (p=0.000), presence of dilatation of CBD (p=0.001) and enhancement pattern (p=0.000) were statistically significant for differentiating PDAC from the other small solid pancreatic tumors, while pancreatic atrophy (p=0.069) was statistically inadequate for differentiation, although it gave a 96.4% specificity for the diagnosis of PDAC. CONCLUSIONS: CT and MRI are similarly accurate in the characterization of small solid pancreatic tumors. Small PDAC has characteristic CT and MRI findings that differentiate it from other small solid tumors.

Predictive value of serum carbohydrate antigen 19-9 in malignant intraductal papillary mucinous neoplasms.

BACKGROUND: The goal of the present study was to evaluate the predictive value of serum carbohydrate antigen 19-9 (CA 19-9) in the diagnosis of malignant intraductal papillary mucinous neoplasms of pancreas (IPMNs). METHODS: Eighty-six patients with pathological diagnosis of IPMNs in Zhongshan Hospital between March 1999 and November 2008 were retrospectively reviewed. Data reflecting clinical characteristics, tumor marker level, and prognosis were collected. The potential predictive value of CA 19-9 was analyzed by receiver operating characteristic (ROC) curve. RESULTS: Eighty-six consecutive patients with IPMNs all underwent surgical intervention. A high level of CA 19-9 or carcinoembryonic antigen (CEA) was associated with more advanced stage of malignant IPMNs. Carbohydrate antigen 19-9 was significant for judging malignant IPMNs in the binary logistic regression model (p=0.047). The hazard ratio was 1.014, whose 95.0% confidence interval was 0.91-1.028. Receiver operating characteristic analysis showed that the serum CA 19-9 level had good predictive value for malignant or invasive IPMNs, postoperative survival, and disease-specific recurrence. The area under the curve (AUC) was 0.856, 0.893, 0.815, and 0.857 (p<0.05), respectively. According to the follow-up, mean survival time for groups with CA 19-9>63.60 U/ml was dramatically shorter than that for groups with CA 19-9≤63.60 U/ml (57.38±2.85 versus 29.24±5.82 [months]; p<0.01). CONCLUSIONS: Serum CA 19-9 level has good predictive value for malignant or invasive IPMNs. Patients with CA 19-9 > 63.60 U/ml had poor postoperative prognosis in IPMNs. Preoperative abnormal serum CA 19-9 might be predictive for an aggressive surgical intervention in IPMNs.

[Clinical implication of BRSK2 expression in pancreatic ductal adenocarcinoma].

OBJECTIVE: To investigate the expression of BRSK2 (brain selective kinase 2) in pancreatic ductal adenocarcinoma and to understand its clinical implication. METHODS: Resected tumor specimens of 79 pancreatic ductal adenocarcinoma were collected and paraffin-embedded for prepare. 0.5 microm sections. Immunohistochemical staining was employed to examine the expression pattern of BRSK2 translated protein. Semi-quantitative analysis was used to evaluate the intensity and content of protein expression in tumor tissues. The expression outcome was compared in peri-tumorous tissues and normal pancreatic tissues. Meanwhile, tumor samples were grouped according to their differentiation, TNM stage, with or without vascular or neural invasion. Then the possible relationship was explored between clinical, pathological and survival data and the expression profile of BRSK2 in tumor tissues. RESULTS: BRSK2's expression was weak in normal pancreatic tissues, including islets and minor ducts such as intercalated ducts, intralobular ducts and interlobular ducts. BRSK2's expression was also weak in peri-tumorous tissues. BRSK2's expression was strong in pancreatic ductal adenocarcinomas. It had a close relationship with lymphatic metastasis, distant metastasis, TNM staging as well as peri-pancreatic neural invasion. Tumors with lymphatic metastasis, distant metastasis and peri-pancreatic neural invasion or at later stages showed a higher expression of BRSK2 than those without or those at early stages. However the expression had no correlation with tumor size, differentiation and vascular invasion. The expression of BRSK2 in pancreatic ductal adenocarcinomas was correlated with the prognosis of patients. Those with a higher expression pattern showed a shorter survival period. CONCLUSION: BRSK2 is up-regulated in pancreatic ductal adenocarcinoma. And its expression is correlated with tumor biological behaviors and patient prognosis.

Survival analysis of pancreatic and periampullary collision cancers.

OBJECTIVE: Collision cancers are malignancies in the same organ or anatomical site that comprises at least two different tumor components, with no mixed or transitional area between two components. Collision cancers are very rare in the pancreas and periampullary region. The aim of this study was to analyze the clinical and pathological features and prognosis of collision cancer in the pancreas and periampullary region. METHODS: Patients with collision cancers of the pancreas and periampullary region (n= 10) who had undergone radical surgery were retrospectively studied. Their clinical and pathological features were summarized and the prognostic data were compared with patients with pancreatic adenocarcinomas who underwent radical surgery (n= 87) and with patients with pancreatic or periampullary malignancies who underwent palliative surgery (n= 89). RESULTS: Compared with other cancers at these sites, collision cancer presents no specific clinical features. However, the median survival period of patients with such malignancies was only 10.0 months, which was much less than those with pancreatic adenocarcinomas who underwent radical surgery (27.0 months) and those who received a palliative operation (20.9 months) only. CONCLUSION: Collision cancers of the pancreas and periampullary region are difficult to diagnose preoperatively. Their prognosis is poor even after radical resection and adjuvant chemotherapy were given.