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Purpose. Nonsurgical therapies, including biotherapy, chemotherapy, and liver-directed therapy, provided a limit survival benefit for PNET patients with hepatic metastases. With the development of liver resection technique, there was a controversy on whether to perform a liver resection for these patients. Methods. A computerized search was made of the Medline/PubMed, EMbase, Cochrane Library, and SinoMed (CBM) before March 2018. A meta-analysis was performed to investigate the differences in the efficacy of liver resection and nonliver resection treatments based on the evaluation of morbidity, 30-day mortality, symptom relief rate, and 1-, 3-, and 5-year survival. Two investigators reviewed all included articles and extracted the data of them. The meta-analysis was performed via Review Manager 5.3 software. Results. A total of 13 cohort studies with 1524 patients were included in this meta-analysis. Compared with the nonliver resection group, liver resection group had a longer 1-, 3-, and 5-year survival time and a higher symptom relief with an acceptable mortality and morbidity. Conclusions. Liver resection is a safe treatment and could significantly prolong the long-term prognosis for highly selected patients with resectable liver metastases from PNET. Further randomized, controlled trials are needed.

Xinzhe Yu,1 Wenwen Zhu,2 Yang Di,1 Jichun Gu,1 Zhongyi Guo,1 Hengchao Li,1 Deliang Fu,1 Chen Jin1 1Department of Pancreatic Surgery, Huashan Hospital, Fudan University, Shanghai, 2Institute of Functional Nano & Soft Materials, Collaborative Innovation Center of Suzhou Nano Science and Technology, Soochow University, Suzhou, Jiangsu, China Abstract: Lymphatic metastasis is the major metastatic pattern of pancreatic cancer and considered as an independent risk factor of survival. However, there is still no effective way for the diagnosis and treatment for lymphatic metastases of pancreatic cancer. In this study, using albumin as a carrier of gemcitabine (Gem), further modified by pyropheophorbide-a, we have designed and synthesized a nanoparticle (NP) compound named “pheophorbide-a (P@)-Gem-human serum albumin (HSA)-NPs”. By utilization of its tracer ability of lymphatic metastases, which is triggered by near-infrared irradiation and its visible dying ability, the compound is used for drug delivery tracking, meanwhile as a treating drug, as well as the combined effect of photodynamic therapy and chemotherapy. By the nude mice model of lymphatic metastases of pancreatic cancer (BxPC-3-LN7), we aim to explore the feasibility, effectiveness, and biological safety of diagnosis and treatment for the lymphatic metastases of pancreatic cancer by P@-Gem-HSA-NP, thereby, providing new methods and strategies for the study of nanodrug carrier and research on lymphatic metastases of pancreatic cancer. Keywords: theranostic nanoparticles, chemotherapy, photodynamic therapy, pancreatic cancer, lymphatic metastases, near infrared irradiation

Background Previous researches in pancreatic cancer demonstrated a negative correlation between secreted protein acidic and rich in cysteine (SPARC) expression in primary tumor and survival, but not for SPARC expression in lymph node. In the present study, we aimed to evaluate the SPARC expression in various types of tissues and its impact on patients' prognosis. Methods The expression of SPARC was examined by immunohistochemistry in resected pancreatic cancer specimens. Kaplan-Meier analyses and Cox proportional hazards regression were applied to assess the mortality risk. Results A total of 222 tissue samples from 73 patients were collected to evaluate the SPARC expression, which included 73 paired primary tumor and adjacent normal tissues, 38 paired metastatic and normal lymph nodes. The proportion of positive SPARC expression in metastatic lymph node was high (32/38), whereas in normal lymph node it was negative (0/38). Positive SPARC expression in primary tumor cells was associated with a significantly decreased overall survival ( P =0.007) and disease-free survival ( P =0.003), whereas in other types of tissues it did not show a predictive role for prognosis. Univariate and multivariate analyses both confirmed this significance. Conclusion SPARC can serve a dual function role as both predictor for prognosis and potentially biomarker for lymph node metastasis in resected pancreatic cancer patients.

Steroid hormone receptors activate gene transcription by binding specific DNA sequences and recruiting coactivators to initiate transcription of their target genes. For most nuclear hormone receptors (NRs), the ligand-dependent activation function domain-2 (AF-2), residing in the C-terminal ligand binding domain (LBD), is a primary contributor to the NR transcriptional activity. In contrast to other steroid receptors such as estrogen receptor-α (ERα), the transcriptional activation function of androgen receptor (AR) is thought to be largely dependent on its ligand-independent activation function domain-1 (AF-1) located in its N-terminal domain (NTD). It remains unclear why AR utilizes a different activation function domain from other steroid receptors despite the fact that NRs share similar domain organizations and have a highly conserved DNA binding domain (DBD) and LBD. Here we present cryo-electron microscopic structures of DNA-bound full-length AR and its functional complex structure with its key coactivators, steroid receptor coactivator-3 (SRC-3) and the histone acetyltransferase p300. The structures reveal that androgen-bound full-length AR dimerization follows a unique head-to-head and tail-to-tail manner with all of the domains involved. The DBD and LBD are located at the center of the dimer interface. The NTDs wrap around the LBDs through their unique intra- and inter-molecular N- and C-terminal interactions and connect to each other. We observe that unlike ERα, AR binds a single SRC-3 molecule along with a single p300 molecule. The AR NTD appears to be the primary site for recruitment of both coactivators. The N-terminal region of SRC-3, rather than its receptor interaction domain, is important for this interaction. The structures presented here highlight the importance of the AR NTD for its transcriptional functions and provide a structural basis for understanding the assembly of the AR:coactivator complex and its domain contributions to transcriptional regulation.

Background Solid pseudopapillary tumor of the pancreas (SPTP) is considered to have a low Ki-67 proliferation index, which may explain the generally good clinical outcome. The aim of our study was to evaluate whether Ki-67 has prognostic value in SPTP. Methods A case series study of patients with SPTP treated in our institution from June 2002 to April 2014 was conducted. Prognostic factors for clinical outcomes were analyzed by the use of clinical decision and survival analysis. In addition, we performed a systematic review and pooled analysis to evaluate our results. Results The institutional data included 71 patients (13 male and 58 female) ranging in age from 12 to 64 years (median, 31 years). Three patients developed local recurrence and/or liver metastasis after initial surgery. The 5-year recurrence-free survival rate was 93.6%. One patient died of disease, with the 5-year disease-specific survival rate of 98.5%. Ki-67 index ≥4% was found significantly associated with the survival of SPTP. Twenty-six studies comprising 163 patients were included in the pooled analysis based on our inclusion criteria. A total of 15 cases showed a Ki-67 index ≥4%. Kaplan-Meier survival analysis confirmed that Ki-67 index ≥4% was significantly associated with poorer recurrence-free survival and disease-specific survival (both P Conclusion This study highlighted a potential role of Ki-67 in predicting adverse outcome of patients with SPTP and should be considered as part of routine histological reporting of SPTP.

For most cancer patients, the presence of metastatic lymph nodes usually indicates regional recurrence and poor prognosis. Therefore, lymph node mapping is a requisite for disease staging, prognosis prediction and decision making in the treatment of cancer. Deuteporfin, a second-generation photosensitizer, has a maximum excitation wavelength that can reach the near infrared (NIR) region (650-700 nm). We aimed to take advantage of these aspects of deuteporfin and use it as a fluorescent probe for metastatic lymph node mapping in vivo using NIR fluorescent imaging. In our study, we further investigated whether a photosensitizer could be used as a tracer for metastatic lymph node mapping of pancreatic cancer based on previous reports. Compared to normal tissues, tumor tissues including primary tumors and metastatic lymph nodes had a higher uptake ability of deuteporfin (P

Currently, the use of photosensitizers as tracer agents to detect lymphatic metastases is a developing area of study in the field of pancreatic cancer treatment. In the present study, deuteporfin, a novel photosensitizer, was used as a tracer agent to detect lymphatic metastases in a pancreatic cancer xenograft model. The biodistribution and pharmacokinetics of deuteporfin, following intravenous administration and injection of deuteporfin into the left rear footpad, were investigated in Sprague-Dawley rats. The increased difference in deuteporfin concentration between the cancerous and normal tissues was directly observed through the application of a Wood's lamp. In addition, the highly lymphatic BxPC-3-LN5 human metastatic pancreatic cancer cell line was generated from BxPC-3 cells using a continuous screening and seeding method in vivo. A xenograft model of the BxPC-3-LN5 human pancreatic cancer cell line transplanted into the left rear footpad of nude mice, was established. The effects of deuteporfin as a tracer agent in the detection of lymphatic metastases were then characterized in the pancreatic cancer xenograft model. Following intravenous administration, deuteporfin was rapidly enriched in the pancreas and popliteal fossa lymph nodes compared with that of the left rear footpad administration group. In addition, deuteporfin appeared to be selectively enriched in the cancerous pancreatic lymph nodes of the pancreatic cancer xenograft model. These results indicated that deuteporfin may be developed as a novel photosensitizer tracer agent for the detection of lymphatic metastases in pancreatic cancer. The advantages of deuteporfin are that it has a selective tumor-targeting effect due to high tissue uptake, and that it may be administered intravenously and is therefore suitable for surgery.

Objective The objectives of this systematic review and meta-analysis were to examine morbidity, mortality, and long-term survival after surgical resection of hepatic metastases from pancreatic ductal adenocarcinoma (PDAC) patients. Background Patients with hepatic metastases from pancreatic ductal adenocarcinoma are facing a dilemma of whether to make hepatic resection. Methods A systematic literature research was undertaken through computerized databases as well as manually research from unpublished data. A meta-analysis was performed to investigate the differences in the efficacy of liver resection and non-surgical treatments based on the evaluation of morbidity, 30-day mortality, and 1-, 3-, or 5-year survival. Results 11 cohort studies with 1147 patients were identified in the pool. Compared with the non-surgical approach, hepatic resection can be performed in a safe and feasible manner for all pancreatic cancer patients with liver metastases ( p = 0.13 for overall morbidity; p = 0.63 for mortality). For surgical group, the median 1-year, 3-year, and 5-year survival were 40.9%, 13.3%, 2.9%, respectively, with a median survival of 9.9 months. Surgical resection of hepatic metastases was associated with a significantly improved overall 1-year and 3-year survival ( p Conclusions Hepatic resection is a safe procedure; furthermore, it is worth doing such an extended surgery for PDAC patients due to additional survival benefit in the medium-term (less than 3 years). However, further randomized, controlled trials are urgently needed.

Pancreaticoduodenectomy combined with portal-superior mesenteric vein synchronous resection for cancer remains a hot debate topic. The present study used meta-analytical technique to provide update information and an evidence-based evaluation on both the perioperative benefit and long-term survival.A meta-analysis was performed to evaluate studies comparing venous resection (VR) versus without venous resection (WVR) groups. 22 retrospective studies including 2890 patients were eligible for an analysis of perioperative morbidity, mortality, and long-term survival. Furthermore, subgroup analysis was made according to histopathology and resection margin status respectively for the purpose of survival assessment.There was no difference in perioperative morbidity, mortality and 1-year, 3-year survival between two groups, but showed differences in median tumor size (P0.001), R0 resection rate (P0.001), lymph node metastasis (P = 0.03), pancreatic fistula (P = 0.01), and 5-year survival (P = 0.03). In subgroup analysis, patients in venous resection group received R0 resection had a significantly better survival comparing with who received R1 resection both at 2-year (P0.001) and 5-year (P = 0.00002). In histopathology subgroup, patients in venous resection groups who had true tumor infiltration had a significantly bad survival comparing with whom only with inflammation pathology.Pancreaticoduodenectomy combined with venous resection can achieve equal perioperative morbidity and mortality as standard resection. However, in order to obtain an optimal survival outcome, surgeons should make an R0 resection as far as possible, especially in cases need synchronous venous resection.

No ideal serum biomarker currently exists for the early diagnosis of colorectal cancer (CRC). Magnetic bead-based fractionation coupled with MALDI-TOF MS was used to screen serum samples from CRC patients, healthy controls, and other cancer patients. A diagnostic model with five proteomic features (m/z 1778.97, 1866.16, 1934.65, 2022.46, and 4588.53) was generated using Fisher algorithm with best performance. The Fisher-based model could discriminate CRC patients from the controls with 100% (46/46) sensitivity and 100% (35/35) specificity in the training set, 95.6% (43/45) sensitivity and 83.3% (35/42) specificity in the test set. We further validated the model with 94.4% (254/269) sensitivity and 75.5% (83/110) specificity in the external independent group. In other cancers group, the Fisher-based model classified 25 of 46 samples (54.3%) as positive and the other 21 as negative. With FT-ICR-MS, the proteomic features of m/z 1778.97, 1866.16, 1934.65, and 2022.46, of which intensities decreased significantly in CRC, were identified as fragments of complement C3f. Therefore, the Fisher-based model containing five proteomic features was able to effectively differentiate CRC patients from healthy controls and other cancers with a high sensitivity and specificity, and may be CRC-specific. Serum complement C3f, which was significantly decreased in CRC group, may be relevant to the incidence of CRC. J. Cell. Biochem. 114: 448–455, 2013. © 2012 Wiley Periodicals, Inc.

Over the past three decades, tremendous progress has been made in cancer prevention and treatment. Despite these advances, a substantial number of cancer cases experience early recurrence and metastases. Thus, the better management of cancer, especially developing more effective drugs for combating cancer cells, is an arduous task. Albumin-based nanoparticles are emerging as a promising approach to replace the traditional way of carrying therapeutic drugs to a tumor site. In this review, we describe the basic knowledge on albumin-based nanoparticles, recent progress of using albumin-based nanoparticles in the diagnosis and treatment of cancer, and the application of nanoparticle albumin bound (Nab) paclitaxel for the treatment of lung, breast and pancreatic cancer. Last but not least, we try to discuss future goals and perspectives in the field of drug delivery research, thereby facilitating the antitumor activity.

Splenic preservation can be achieved through splenic vessel resection by Warshaw’s technique (WT) or by preserving the splenic vessels. This meta-analysis aims to provide evidence-based comparison regarding the perioperative outcome and long-term benefits between patients with and without splenic vessel preservation (SVP) during spleen-preserving distal pancreatectomy. A meta-analysis was performed to evaluate studies comparing splenic vessel preservation versus resection groups. Ten retrospective studies including 699 patients were eligible for an analysis of general, perioperative, and long-term outcomes. A further analysis composed of five subgroups was also conducted in terms of laparoscopic approach. Warshaw’s technique related to significant shorter operation time (P

s / Pancreatology 16 (2016) S1eS63 S43 Lymph node mapping is crucial for decision making in cancer treatment. Deuteporfin, with a maximum excitation wavelength can reach nearinfrared region. Metastatic lymph node has a higher uptake ability of deuteporfin We firstly report deuteporfin can be used for metastatic lymph node mapping. We confirm this targeting property of deuteporfin by in vivo fluorescent imaging.

e15231 Background: Previous researches in pancreatic cancer demonstrated a negative correlation between SPARC expression in the primary tumor and survival benefit, but not for lymph node SPARC expr...

e15266 Background: The preoperative identification of pancreatic cystic neoplasms (PCNs) is crucial to the surgical decision-making. Besides pursuing better imaging and laboratory techniques, this ...