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Cancer of the Pancreas

Pancreatic cancer is a disease in which the cells of the pancreas become malignant. The pancreas has two main functions; (i) it makes juices that help digest food and (ii) produces hormones (including insulin) that conrol how food is used and stored in the body. The vast majority of pancreatic cancers are associated with the part of the pancreas that makes digestive juices - these are known as "exocrine" pancreatic cancers. Only about 1/20 pancreatic cancers start in the hormone producing part of the pancreas ; these are known as "endocrine" pancreatic cancer or "islet cell cancer". There are several types of exocrine pancreatic cancers (based on how the cells appear under the microsope), most are classed as "ductal adenocarcinomas". Pancreatic cancer is rare before the age of 40 years, incidence increases sharply with increasing age.

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Pancreatic Neuroendocrine Tumours (Islet Cell Tumours)
Familial Pancreatic Cancer

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  • PubMed search for publications about Pancreatic Cancer - Limit search to: [Reviews]

    PubMed Central search for free-access publications about Pancreatic Cancer
    MeSH term: Pancreatic Neoplasms
    International US National Library of Medicine
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Latest Research Publications

This list of publications is regularly updated (Source: PubMed).

Serrano PE, Kim D, Kim PT, et al.
Effect of Pancreatic Fistula on Recurrence and Long-Term Prognosis of Periampullary Adenocarcinomas after Pancreaticoduodenectomy.
Am Surg. 2016; 82(12):1187-1195 [PubMed] Related Publications
Pancreatic fistula (PF) is common after pancreaticoduodenectomy (PD). Its effect on recurrence and survival is not known. Retrospective study of patients undergoing PD for periampullary adenocarcinomas (2000-2012). Standard statistical analyses were performed to determine the impact of PF on disease-free survival (DFS) and overall survival (OS). There were 634 PDs (pancreatic adenocarcinoma: 347, other periampullary adenocarcinomas: 287). Any-grade PF developed in 81/634 (13%). Perioperative mortality rate was 1.7 per cent (11/634), higher in patients with PF (10 vs 0.5%, P < 0.001). In multivariable analysis, PF significantly reduced DFS in pancreatic [hazard ratio (HR) = 1.6, 95% confidence-interval (CI): 1.1-2.6, P = 0.043] but not in other periampullary adenocarcinomas [HR = 1.3 (95% CI: 0.8-2.2), P = 0.45]. Positive lymph nodes, margins, and high-grade histology were associated with decreased DFS and OS. Adjuvant therapy was associated with improved OS in pancreatic [HR = 0.7 (95% CI: 0.5-0.9), P = 0.02] but not in other periampullary adenocarcinomas [HR = 1.14 (95% CI: 0.8-1.7), P = 0.49]. PF did not alter OS in either group. After PD, PF is associated with decreased DFS in pancreatic but not in other periampullary adenocarcinomas. This decrease DFS did not alter OS. Tumor grade, lymph nodes, and resection margin status are associated with DFS and OS.

Yue Q, Gao G, Zou G, et al.
Natural Products as Adjunctive Treatment for Pancreatic Cancer: Recent Trends and Advancements.
Biomed Res Int. 2017; 2017:8412508 [PubMed] Free Access to Full Article Related Publications
Pancreatic cancer is a type of common malignant tumors with high occurrence in the world. Most patients presented in clinic had pancreatic cancer at advanced stages. Furthermore, chemotherapy or radiotherapy had very limited success in treating pancreatic cancer. Complementary and alternative medicines, such as natural products/herbal medicines, represent exciting adjunctive therapies. In this review, we summarize the recent advances of using natural products/herbal medicines, such as Chinese herbal medicine, in combination with conventional chemotherapeutic agents to treat pancreatic cancer in preclinical and clinical trials.

Johnson MD, Stone B, Thibodeau BJ, et al.
The significance of Trk receptors in pancreatic cancer.
Tumour Biol. 2017; 39(2):1010428317692256 [PubMed] Related Publications
This study investigated the Trk receptor family as a therapeutic target in pancreatic ductal adenocarcinoma and assessed their prognostic significance. Global gene expression analysis was investigated in prospectively collected pancreatic ductal adenocarcinomas that had either undergone neoadjuvant chemoradiation or were treated by surgery. PANC-1 and MIA-PaCa-2 cell lines were investigated to establish whether fractionated radiation altered expression of four neuroendocrine genes and whether this resulted in subsequent changes in radiosensitivity. A specific inhibitor of TrkA, B, and C, AstraZeneca 1332, was investigated in vitro and in vivo in combination with radiation. A tissue microarray was constructed from 77 pancreatic ductal adenocarcinoma patients who had undergone neoadjuvant chemoradiation and the Trk receptor, and neurogenic differentiation 1 expression was assessed and correlated with overall survival. A total of 99 genes were identified that were differentially expressed in the chemoradiation patients with neuroendocrine genes and pathways, in particular the neurogenic differentiation 1 and Trk receptor family, being prominent. Fractionated radiation upregulated the expression of neuroendocrine genes, and AstraZeneca 1332 treatment in vitro enhanced radiosensitivity. No added effect of AstraZeneca 1332 was observed in vivo. Trk receptor expression varied between isoforms but did not correlate significantly with clinical outcome. Radiation treatment upregulated neuroendocrine gene expression but the Trk receptor family does not appear to be a promising treatment target.

Guo R, Gu J, Zhang Z, et al.
MiR-451 Promotes Cell Proliferation and Metastasis in Pancreatic Cancer through Targeting CAB39.
Biomed Res Int. 2017; 2017:2381482 [PubMed] Free Access to Full Article Related Publications
Emerging evidence shows that microRNAs (miRNAs) play important roles in the regulation of various biological and pathologic processes in human cancers and the aberrant expression of miRNAs contributes to the tumor development. In this study, our findings indicate that miR-451 is significantly overexpressed in pancreatic cancer tissues and cell lines and elevated expression of miR-451 contributes to promoted cell viability (in vitro and in vivo). Moreover, overexpression of miR-451 is closely linked to poor prognosis and lymphatic metastasis. Inhibition of miR-451 dramatically suppresses cell viability and invasion, promotes cell apoptosis, and induces cell cycle arrest. Furthermore, miR-451 directly targets CAB39 and negatively regulates its expression and inhibition of CAB39 contributes to the promoted cell viability and invasion. Our findings improve our understanding of the function of miR-451 in the identification and therapy of pancreatic cancer.

Okada KI, Hirono S, Kawai M, et al.
Phase I Study of Nab-Paclitaxel plus Gemcitabine as Neoadjuvant Therapy for Borderline Resectable Pancreatic Cancer.
Anticancer Res. 2017; 37(2):853-858 [PubMed] Related Publications
BACKGROUND/AIM: The aim of this study was to investigate the safety and feasibility of neoadjuvant nab-paclitaxel plus gemcitabine therapy for patients with borderline resectable pancreatic carcinoma (BRPC).
PATIENTS AND METHODS: The study was a prospective single-center phase I trial for patients with BRPC. The primary endpoint was the toxicity, and secondary endpoints were the resection rate, the R0 resection rate and quality of life (QOL) regarding the peripheral sensory neuropathy (PSN). This trial was registered on the UMIN Clinical Trials Registry (UMIN000018382) and on ClinicalTrials.gov (NCT02506803).
RESULTS: The overall rate of any grade and grade 3-4 events (CTCAE ver. 4.0 criteria) were 100% and 90%. The majority of these adverse events represented expected neutropenia. The resection and R0 resection rates were 80% and 70%, respectively.
CONCLUSION: We found that neoadjuvant nab-paclitaxel plus gemcitabine therapy was safe and feasible without stringent selection of patients with BRPC.

Shirai Y, Shiba H, Haruki K, et al.
Preoperative Platelet-to-Albumin Ratio Predicts Prognosis of Patients with Pancreatic Ductal Adenocarcinoma After Pancreatic Resection.
Anticancer Res. 2017; 37(2):787-793 [PubMed] Related Publications
BACKGROUND: The aim of this study was to evaluate a novel prognostic value of preoperative platelet-to-albumin ratio (PAR) in patients resected for pancreatic cancer.
PATIENTS AND METHODS: A total of 107 patients who underwent pancreatic resection for pancreatic cancer were studied. The patients were divided into two groups as PAR ≥46.4×10(3) or <46.4×10(3) Survival data were analyzed using the log-rank test for univariate analysis and Cox proportional hazards for multivariate analysis.
RESULTS: The PAR was a significant prognostic index on univariate analysis for disease-free survival (DFS) and overall survival (OS). The PAR retained its significance on multivariate analysis for OS (hazard ratio(HR)=2.344, 95% confidence interval(CI)=1.188-4.624, p=0.014) along with tumor differentiation and nodal involvement. PAR was a significant independent prognostic index for poor DFS on multivariate analysis (HR=1.971, 95% CI=1.128-3.444, p=0.017).
CONCLUSION: The preoperative PAR is a novel significant independent prognostic index for DFS and OS in patients after pancreatic resection with curative intent.

Park S, Kim SC, Hong SM, et al.
Postoperative Radiotherapy for Pancreatic Cancer with Microscopically-positive Resection Margin.
Anticancer Res. 2017; 37(2):755-764 [PubMed] Related Publications
AIM: To analyze the outcomes in pancreatic cancer (PC) cases with a microscopically-positive resection margin (R1 resection) treated with postoperative radiotherapy (PORT).
PATIENTS AND METHODS: We retrospectively analyzed the outcomes in 62 patients who received PORT for PC with R1 resection between 2001 and 2012. All patients received three-dimensional conformal radiotherapy. Concurrent chemotherapy was administered to 58 patients.
RESULTS: The median follow-up was 20.1 months. The median survival was 22.0 months and the 3-year overall survival rate was 25%. The 3-year disease-free survival and local recurrence-free survival rates were 12% and 54%, respectively. Local recurrence occurred in 23 patients (44%), distant failure in 45 (87%), and both in 16 (31%). By multivariate analysis, the postoperative cancer antigen 19-9 (CA19-9) level and adjuvant chemotherapy were independent prognostic factors for survival.
CONCLUSION: PORT is associated with a relatively favorable survival outcome in PC with R1 resection. Chemotherapy and postoperative CA19-9 level were significant prognostic factors for survival.

Klein F, Denecke T, Faber W, et al.
DNA Cytometry for Differentiation Between Low- and Medium-grade Dysplasia in Intraductal Papillary Mucinous Neoplasms.
Anticancer Res. 2017; 37(2):735-740 [PubMed] Related Publications
BACKGROUND/AIM: The indication for resection of cystic pancreatic lesions is usually performed by sectional imaging criteria, such as the Sendai criteria. The aim of this study was to analyze a possible correlation between DNA cytometry and Sendai criteria for the differentiation between low-grade intraductal papillary mucinous neoplasms (IPMN-A) and medium-grade dysplasia (IPMN-B).
MATERIALS AND METHODS: Histopathological analysis, DNA index and preoperative Sendai criteria were determined in 16 patients who underwent pancreatic resection for IPMN.
RESULTS: All patients with IPMN-B showed aneuploid histograms with DNA indices ≥1.3, whereas three out of four patients with IPMN-A had diploid DNA indices ≤1.3. All 11 patients with one or more high-risk stigmata and aneuploid histograms had IPMN-Bs, whereas both patients who were Sendai-negative and diploid in the DNA analysis had an IPMN-A.
CONCLUSION: DNA index may be an important diagnostic tool for the differentiation of different IPMN types beyond the traditional Sendai criteria.

Backman S, Norlén O, Eriksson B, et al.
Detection of Somatic Mutations in Gastroenteropancreatic Neuroendocrine Tumors Using Targeted Deep Sequencing.
Anticancer Res. 2017; 37(2):705-712 [PubMed] Related Publications
Mutations affecting the mechanistic target of rapamycin (MTOR) signalling pathway are frequent in human cancer and have been identified in up to 15% of pancreatic neuroendocrine tumours (NETs). Grade A evidence supports the efficacy of MTOR inhibition with everolimus in pancreatic NETs. Although a significant proportion of patients experience disease stabilization, only a minority will show objective tumour responses. It has been proposed that genomic mutations resulting in activation of MTOR signalling could be used to predict sensitivity to everolimus.
PATIENTS AND METHODS: Patients with NETs that underwent treatment with everolimus at our Institution were identified and those with available tumour tissue were selected for further analysis. Targeted next-generation sequencing (NGS) was used to re-sequence 22 genes that were selected on the basis of documented involvement in the MTOR signalling pathway or in the tumourigenesis of gastroenterpancreatic NETs. Radiological responses were documented using Response Evaluation Criteria in Solid Tumours.
RESULTS: Six patients were identified, one had a partial response and four had stable disease. Sequencing of tumour tissue resulted in a median sequence depth of 667.1 (range=404-1301) with 1-fold coverage of 95.9-96.5% and 10-fold coverage of 87.6-92.2%. A total of 494 genetic variants were discovered, four of which were identified as pathogenic. All pathogenic variants were validated using Sanger sequencing and were found exclusively in menin 1 (MEN1) and death domain associated protein (DAXX) genes. No mutations in the MTOR pathway-related genes were observed.
CONCLUSION: Targeted NGS is a feasible method with high diagnostic yield for genetic characterization of pancreatic NETs. A potential association between mutations in NETs and response to everolimus should be investigated by future studies.

Grace SA, Meeks MW, Chen Y, et al.
Adipose Triglyceride Lipase (ATGL) Expression Is Associated with Adiposity and Tumor Stromal Proliferation in Patients with Pancreatic Ductal Adenocarcinoma.
Anticancer Res. 2017; 37(2):699-703 [PubMed] Related Publications
BACKGROUND: Obesity is an established risk factor for the development of pancreatic ductal adenocarcinoma (PDAC). However, the pathophysiology of how increased adiposity increases the risk for PDAC has not been fully elucidated. Adipose triglyceride lipase (ATGL) is a lipase that catabolizes triglyceride hydrolysis and has been implicated in the development of breast cancer. We hypothesized that overweight patients with PDAC would demonstrate higher tumor ATGL expression compared to non-overweight patients with PDAC.
MATERIALS AND METHODS: Immunohistochemical analysis for ATGL expression was performed on PDAC tissues from 44 patients after Whipple procedure or distal pancreatectomy. Correlation of ATGL expression with clinicopathological features was evaluated.
RESULTS: A total of 23/44 (52.2%) PDACs showed low level ATGL immunoreactivity, while 21/44 (47.8%) showed a high level, with moderate to strong positive ATGL immunoreactivity in more than 50% of the tumor cells. Chi-squared testing revealed a statistically significant association between high ATGL expression and both BMI >25 kg/m(2) (χ(2)=5.74, p=0.017) and increased tumor stroma (χ(2)=19.14, p<0.001). Chi-squared testing failed to reveal a statistically significant association when comparing ATGL expression by lymph node metastasis, histological grade, tumor size, patient age, patient sex and presence of fat invasion.
CONCLUSION: Our results suggest that increased ATGL expression is associated with increased adiposity and stromal proliferation in patients with PDAC, making it a possible key protein in how obesity increases the risk of PDAC.

Murata Y, Kokuryo T, Yokoyama Y, et al.
The Anticancer Effects of Novel α-Bisabolol Derivatives Against Pancreatic Cancer.
Anticancer Res. 2017; 37(2):589-598 [PubMed] Related Publications
Pancreatic cancer is highly malignant, characterized by aggressive proliferation, invasion, and metastasis. α-Bisabolol is an oily sesquiterpene alcohol derived from a variety of plants. We previously demonstrated that α-bisabolol is a potential therapeutic agent for pancreatic cancer. The aim of this study was to develop α-bisabolol derivatives which are more potent than the parent compound and may be clinically useful against pancreatic cancer. First, 22 derivatives of α-bisabolol were designed and synthesized. α-Bisabolol derivatives 4 and 5 had more potent inhibitory effects on the proliferation of pancreatic cancer cells than did α-bisabolol. Next, 15 additional α-bisabolol derivatives were designed and synthesized based on the structure of α-bisabolol derivatives 4 and 5 Among them, α-bisabolol derivative 5 had the strongest inhibitory effect on proliferation. This novel compound reduced the proliferation of various pancreatic cancer cell lines, such as KLM1, Panc1, and KP4. In addition, the compound induced higher levels of apoptosis in pancreatic cancer cell lines than did α-bisabolol. α-Bisabolol derivative 5 inhibited xenograft tumor growth and reduced dissemination of pancreatic cancer to peritoneal nodules. The compound strongly suppressed AKT expression in the peritoneal nodules. Reduced AKT expression in peritoneal nodules is consistent with an anticancer effect. These data indicate that α-bisabolol derivative 5 effectively prevents the progression of pancreatic cancer via inhibition of AKT. Taken together, the results showed that this compound has attractive therapeutic properties as a novel anticancer drug for pancreatic cancer.

Nanjappa S, Singh V, Uttamchandani S, Pabbathi S
Thrombotic Microangiopathy in a Patient Treated With Gemcitabine.
Cancer Control. 2017; 24(1):54-56 [PubMed] Related Publications
Thrombotic microangiopathy syndromes consist of a collection of disorders with a varied etiology that share common clinical and pathological features. Although thrombotic microangiopathy is rare, it is associated with significant morbidity and mortality. Without early recognition and intervention, the prognosis of the disease is poor. This report illustrates the case of a 56-year-old man with advanced-stage metastatic pancreatic cancer who presented with hemolytic uremic syndrome associated with gemcitabine use. His condition was managed with eculizumab, a monoclonal antibody, although he was dependent on dialysis. This report reflects the importance of considering thrombotic microangiopathy syndromes in the differential diagnosis, because many malignancies and use of chemotherapeutic agents can trigger hemolytic uremic syndrome.

Montanier N, Joubert-Zakeyh J, Pétorin C, et al.
The prognostic influence of the proliferative discordance in metastatic pancreatic neuroendocrine carcinoma revealed by peptide receptor radionuclide therapy: Case report and review of literature.
Medicine (Baltimore). 2017; 96(6):e6062 [PubMed] Free Access to Full Article Related Publications
RATIONALE: Pancreatic neuroendocrine tumors (pNET) are rare slowly growing tumors with a high metastatic potential. Peptide receptor radionuclide therapy (PRRT) with radiolabeled analogues has been developed as a new tool for the management of metastatic well-differentiated (grade 1 and 2) neuroendocrine tumors expressing somatostatin receptor (SSTR2). Chemotherapy is the mainstay in the management of grade 3 (G3) unresectable pancreatic neuroendocrine carcinoma (pNEC). To date, no study has evaluated the efficacy of PRRT in such tumors.
DIAGNOSES AND INTERVENTIONS: We describe a case of a progressive G3 pNEC with huge liver metastases successfully treated with PRRT (Lu DOTATATE).
OUTCOMES: Complete remission was obtained for 3 years. Indeed, the mitotic index was low (as G2 tumors) but with a very high Ki-67 index (45%-70%). Such discordance between the proliferative markers should consider the use of PRRT before chemotherapy in unresectable metastatic G3 tumors expressing SSTR2.
LESSONS: This case supports the hypotheses highlighting the heterogeneity of G3 pNEC. The latter should be subdivided into 2 distinct categories: proliferation-discordant (well differentiated) and concordant (poorly differentiated) NEC. PRRT could be suggested for the former group before the conventional chemotherapy.

Shimizu Y, Imaizumi H, Yamauchi H, et al.
Pancreatic Fistula Extending into the Thigh Caused by the Rupture of an Intraductal Papillary Mucinous Adenoma of the Pancreas.
Intern Med. 2017; 56(3):307-313 [PubMed] Related Publications
We herein report the first case of a pancreatic fistula extending into the thigh caused by the rupture of an intraductal papillary mucinous neoplasm (IPMN) of the pancreas. An 80-year-old man was suspected to have necrotizing fasciitis because of right femoral pain. Computed tomography showed fluid retention from the pancreatic head to the right iliopsoas muscle and an IPMN at the pancreatic head. The findings of endoscopic retrograde pancreatography led to the suspicion of a minor leak and a pancreatic stent was placed. The patient died due to an uncontrollable infection. A pathological autopsy showed a pancreatic fistula extending into the thigh that had been caused by the rupture of the IPMN.

Sano I, Katanuma A, Yane K, et al.
Pancreatic Metastasis from Rectal Cancer that was Diagnosed by Endoscopic Ultrasonography-guided Fine Needle Aspiration (EUS-FNA).
Intern Med. 2017; 56(3):301-305 [PubMed] Related Publications
Pancreatic metastasis from colorectal cancer is rare, and there have been only a few reports of its preoperative diagnosis by endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) with immunohistochemical staining. We herein describe the case of a 77-year-old woman in whom a solitary mass in the pancreatic tail was detected 11 years after rectal cancer resection. The patient also had a history of pulmonary tumor resection. We performed EUS-FNA and a histopathological examination showed adenocarcinoma with CD20+, CD7-, and CDX2+ (similar to her rectal cancer). EUS-FNA enabled a histopathological examination, including immunohistochemical staining, which helped to confirm the diagnosis of pancreatic and pulmonary metastasis from rectal cancer.

Kim HW, Lee JC, Paik KH, et al.
Serum interleukin-6 is associated with pancreatic ductal adenocarcinoma progression pattern.
Medicine (Baltimore). 2017; 96(5):e5926 [PubMed] Free Access to Full Article Related Publications
Several reports showed that interleukin-6 (IL-6) or -8 (IL-8) might be useful inflammatory biomarkers for pancreatic ductal adenocarcinoma (PDAC), although these clinical impact is still open to debate. The aim of this study was to elucidate whether serum levels of IL-6 and IL-8 at diagnosis could predict the tumor progression pattern of PDAC, especially in extensive hepatic metastasis.According to the tumor burden of hepatic metastasis at the last follow-up, tumor progression pattern was defined as follows: no or limited (unilobar involvement and 5 or less in the within liver, limited group) and extensive hepatic metastasis (bilobar or more than 5, progressed group). Fifty-three PDAC patients with initially no or limited hepatic metastasis were enrolled retrospectively.Around 42 (79.2%) were included in the limited and 11 (20.8%) in the progressed group. The median serum level of IL-6 in the progressed group was elevated significantly compared with the limited group. However, the median serum level of IL-8 was not. Furthermore, multivariate analysis revealed that the elevated serum level of IL-6 was an independent risk factor for progression to extensive hepatic metastasis (odds ratio 1.928, 95% confidence interval 1.131-3.365, P = 0.019), but IL-8 was not. However, higher IL-6 did not predict shorter survival.High serum IL-6 can be an independent risk factor for progression to extensive hepatic metastasis in PDAC patients.

Han Q, Deng M, Lv Y, Dai G
Survival of patients with advanced pancreatic cancer after iodine125 seeds implantation brachytherapy: A meta-analysis.
Medicine (Baltimore). 2017; 96(5):e5719 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Brachytherapy with iodine-labeled seeds (I-seeds) implantation is increasingly being used to treat tumors because of its positional precision, minimal invasion, least damage to noncancerous tissue due to slow and continuous release of radioactivity and facilitation with modern medical imaging technologies. This study evaluates the survival and pain relief outcomes of the I-seeds implantation brachytherapy in advanced pancreatic cancer patients.
METHODS: Literature search was carried out in multiple electronic databases (Google Scholar, Embase, Medline/PubMed, and Ovid SP) and studies reporting I seeds implantation brachytherapy in pancreatic cancer patients with unresectable tumor were selected by following predetermined eligibility criteria. Random effects meta-analysis was performed to achieve inverse variance weighted effect size of the overall survival rate after the intervention. Sensitivity and subgroups analyses were also carried out.
RESULTS: Twenty-three studies (824 patients' data) were included in the meta-analysis. I-seeds implantation brachytherapy alone was associated with 8.98 [95% confidence interval (CI): 6.94, 11.03] months (P < 0.00001) overall survival with 1-year survival of 25.7 ± 9.3% (mean ± standard deviation; SD) and 2-year survival was 17.9 ± 8.6% (mean ± SD). In stage IV pancreatic cancer patients, overall survival was 7.13 [95% CI: 4.75, 9.51] months (P < 0.00001). In patients treated with I-seeds implantation along with 1 or more therapies, overall survival was 11.75 [95% CI: 9.84, 13.65] months (P < 0.00001) with 1-year survival of 47.4 ± 22.75% (mean ± SD) and 2-year survival was 16.97 ± 3.1% (mean ± SD). I-seeds brachytherapy was associated with relief of pain in 79.7 ± 9.9% (mean ± SD) of the patients.
CONCLUSIONS: Survival of pancreatic cancer patients after I-seeds implantation brachytherapy is found to be 9 months, whereas a combined treatment with I-seeds brachytherapy and other therapies was associated with approximately 12 months' survival. The majority of patients who underwent I-seeds brachytherapy had their pain relieved.

Akatsu Y, Yoshimatsu Y, Tomizawa T, et al.
Dual targeting of vascular endothelial growth factor and bone morphogenetic protein-9/10 impairs tumor growth through inhibition of angiogenesis.
Cancer Sci. 2017; 108(1):151-155 [PubMed] Free Access to Full Article Related Publications
Clinical development of anti-angiogenic agents has been a major landmark in cancer therapy for several types of cancers. Signals mediated by both vascular endothelial growth factor (VEGF) and bone morphogenetic protein (BMP)-9 and 10 have been implicated in tumor angiogenesis. However, previous studies have shown that targeting the individual signals was not sufficiently effective in retarding tumor growth in certain preclinical and clinical conditions. In the present study, we developed a novel decoy chimeric receptor that traps both VEGF and BMP-9/10. Single targeting of either VEGF or BMP-9/10 signals significantly reduced the formation of tumor vessels in a mouse xenograft model of human pancreatic cancer; however, it did not show significant therapeutic effects on tumor growth. In contrast, dual targeting of the angiogenic signals resulted in more significant inhibition of tumor angiogenesis, leading to delay of tumor growth. Our findings suggest that simultaneous blockade of VEGF and BMP-9/10 signals is a promising therapeutic strategy for the cancers that are resistant to anti-VEGF and BMP-9/10 therapies.

Pendola F, Gadde R, Ripat C, et al.
Distal pancreatectomy for benign and low grade malignant tumors: Short-term postoperative outcomes of spleen preservation-A systematic review and update meta-analysis.
J Surg Oncol. 2017; 115(2):137-143 [PubMed] Related Publications
BACKGROUND: The value of spleen preservation with distal pancreatectomy (DP) for benign and low grade malignant tumors remains unclear. The aim of this study was to evaluate the short-term postoperative clinical outcomes in patients undergoing DP with splenectomy (DPS) or spleen preservation (SPDP).
METHODS: Online database search was performed (2000 to present); key bibliographies were reviewed. Studies comparing patients undergoing DP with either DPS or SPDP, and assessing postoperative complications were included.
RESULTS: Meta-analysis of included data showed SPDP patients had significantly less operative blood loss, shorter duration of hospitalization, lower incidence of fluid collection and abscess, lower incidence of postoperative splenic and portal vein thrombosis, and lower incidence of new onset postoperative diabetes. For the whole group, there was no difference in incidence of postoperative pancreatic fistula (POPF) (RR = 0.95; 95%CI 0.65-1.40, P = 0.80), however, subgroup analysis of studies using ISGPF criteria showed that DPS patients had increased rates of Grade B/C POPF (RR = 1.35; 95%CI 1.08-1.70, P = 0.01).
CONCLUSIONS: SPDP for benign and low grade malignant tumors is associated with shorter hospital stay and decreased morbidity compared to DPS. J. Surg. Oncol. 2017;115:137-143. © 2017 Wiley Periodicals, Inc.

Nayar P, Chandak A, Gupta N, et al.
Postoperative mortality following multi-modality therapy for pancreatic cancer: Analysis of the SEER-Medicare data.
J Surg Oncol. 2017; 115(2):158-163 [PubMed] Related Publications
BACKGROUND AND OBJECTIVES: The objective of this study was to examine post-operative mortality for elderly pancreatic cancer patients treated with multi-modality therapy.
METHODS: Surveillance Epidemiology and End Results (SEER) Medicare linked data were used to examine differences in mortality between patients who underwent pancreatectomy alone and those who had early (within 12 weeks) and late (after 12 weeks) adjuvant therapy (chemotherapy and/or radiotherapy).
RESULTS: Among 4,105 patients who underwent pancreatectomy between 1991 and 2008, 1-year mortality (Odds Ratio [OR] = 0.71; P-value = 0.000; 95% Confidence Interval [CI]: 0.60-0.85) and 6-month mortality (OR = 0.44; P-value = 0.000; 95%CI: 0.35-0.53) following pancreatectomy were significantly lower in the group that underwent pancreatectomy with early adjuvant therapy. Late adjuvant therapy group also had lower 1 year (OR = 0.51; P-value = 0.000; 95%CI: 0.43-0.61) and 6 months (OR = 0.14; P-value = 0.000; 95%CI: 0.10-0.17) mortality, compared to surgery alone.
CONCLUSIONS: Post-operative outcomes were better for patients treated with surgery with adjuvant therapy, with the late adjuvant therapy group having the best outcomes (lowest odds of 6 month and 1-year mortality following surgery). J. Surg. Oncol. 2017;115:158-163. © 2017 Wiley Periodicals, Inc.

Jia Z, Zhang K, Huang R, et al.
Pancreatic carcinosarcoma with rare long-term survival: Case report and review of the literature.
Medicine (Baltimore). 2017; 96(4):e5966 [PubMed] Free Access to Full Article Related Publications
PATIENT CONCERNS: We report a rare case of pancreatic carcinosarcoma involving a 44-year-old woman. The patient complained of discomfort associated with the upper abdomen and jaundice of skin and sclera for 1 week.
DIAGNOSES: After hospitalization, relevant examinations were completed. The disease was diagnosed as carcinoma of the pancreatic head.
INTERVENTIONS: Whipple procedure was conducted in May 2013. Intraoperative exploration indicated 2 components of the tumor: a fish-shaped gray matter and a hard structure similar to cancellous bone. Histopathological examination showed adenocarcinoma and osteosarcoma. After surgery, the patient received 8 cycles of chemotherapy with gemcitabine and raltitrexed.
OUTCOMES: Previous studies indicated poor prognosis for pancreatic carcinosarcoma. However, our patient survived for 31 months with no recurrence till date.
LESSONS SUBSECTIONS: Coexistence of pancreatic adenocarcinoma and osteosarcoma is very rare. Our case was also an exception in manifesting longer survival than expected.

Kishida Y, Matsubayashi H, Sasaki K, et al.
A case of multicentric pancreatic mixed acinar-ductal carcinoma diagnosed by a yogurt-like cell clump flowing from the papilla of Vater.
BMC Gastroenterol. 2017; 17(1):20 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Histological confirmation is needed when the pancreatic lesions is uncertain for neoplastic or nonneoplastic. Current case with multicentric pancreatic carcinomas showing indefinite clinical images was successfully diagnosed by a biopsy of a novel object expelled from the papilla.
CASE PRESENTATION: A 71-year-old male was referred because of elevated serum pancreatic enzymes. Computed tomography revealed an unclear low-density area in the pancreatic body without evidence of tumor and mild dilation of the upstream main pancreatic duct (MPD). Other images, including abdominal ultrasound, endoscopic ultrasound, and magnetic resonance imaging, did not demonstrate cancerous findings. Endoscopic retrograde cholangiopancreatography showed a crab-claw-like obstruction in the MPD. Surprisingly, the component constituting the obstruction was moved by contrast injection and spilled out of the papilla orifice as a yogurt-like white object. Biopsy of this object by histology revealed a cancer cell clump. Pancreatectomy was performed, and pathology of the resected pancreas showed multiple nodular tumors replacing the acini and extending into the MPD. These neoplasms histologically resembled mixed acinar-ductal carcinoma.
CONCLUSION: Current report presented a rare tumor with multicentric pancreatic lesions, preoperatively diagnosed by a biopsy of an uncommon substance.

Zhou J, Xin C, Xia T, et al.
Laparoscopic pancreaticoduodenectomy in A-92-older Chinese patient for cancer of head of the pancreas: A Case report.
Medicine (Baltimore). 2017; 96(3):e5962 [PubMed] Free Access to Full Article Related Publications
INTRODUCTION: Laparoscopic pancreaticoduodenectomy (LPD) is one of the most complex gastrointestinal procedures performed in laparoscopic abdominal surgery. However, the concern for elderly undergoing LPD remains. To the best of our knowledge, there are no reports describing LPD for A-92-older patient. This study aimed to share the experience of a tertiary pancreatic center and confirm the safety, feasibility of LPD for the elderly.
METHOD: The patient had complained of 6-months history of abdominal discomfort and progressive jaundice. Abdominal computed tomography CT/MR imaging revealed a 3 × 3 cm solid hypovascular mass in the head of the pancreas. LPD was successfully performed after multidisciplinary team (MDT). Operation time was 450 minutes, and blood loss was 120 mL. Histological examination of the resected specimen confirmed the diagnosis of pancreatic ductal adenocarcinoma (PDAC).
OUTCOMES: The patient was discharged on POD13 following an uneventful postoperative period. She was followed up 4 months without any sign of recurrence.
CONCLUSION: LPD can be performed safely in patients of any age who are fit for surgery in specialist centers.

Li S, Tian B
Acute pancreatitis in patients with pancreatic cancer: Timing of surgery and survival duration.
Medicine (Baltimore). 2017; 96(3):e5908 [PubMed] Free Access to Full Article Related Publications
Acute pancreatitis (AP) is a rare manifestation of pancreatic cancer (PC). The relationship between AP and PC remains less distinct.From January 2009 to November 2015, 47consecutive patients with PC who presented with AP were reviewed for this study. Clinical features, clinicopathologic variables, postoperative complications, and follow-up evaluations of patients were documented in detail from our database. In order to identify cutoff threshold time for surgery, receiver operating curve (ROC) was built according to patients with or without postoperative complications. Cumulative rate of survival was calculated by using the Kaplan-Meier method. The study was conducted in accordance with the principles of the Declaration of Helsinki and the guidelines of West China Hospital.This study included 35 men (74.5%) and 12 women (25.5%) (mean age: 52 years), with a median follow-up of 40 months. AP was clinically mild in 45 (95.7%) and severe in 2 (4.3%). The diagnosis of PC was delayed by 2 to 660 days (median 101 days). Thirty-nine (83.0%) cases underwent surgery. Eight (17.0%) cases performed biopsies only. Of 39 patients, radical surgery was performed in 32 (82.1%) cases and palliative in 7 (19.9%) cases. Two (8.0%) patients were needed for vascular resection and reconstruction. Postoperative complications occurred in 12 (30.8%) patients. About 24.5 days was the best cutoff point, with an area under curve (AUC) of 0.727 (P = 0.025, 95% confidence interval: 0.555-0.8999). The survival rate of patients at 1 year was 23.4%. The median survival in patients with vascular resection and reconstruction was 18 months, compared with 10 months in patients without vascular resection (P = 0.042). For the primary stage (T), Tix was identified in 3 patients, the survival of whom were 5, 28, 50 months, respectively. And 2 of them were still alive at the follow-up period.The severity of AP was mainly mild. Surgical intervention after 24.5 days may benefit for reducing postoperative complications. Patients with vascular resection and reconstruction, thus achieving tumor-free margins, had a long-time survival.

Hennessy G, Vamadevan S, Loh H, et al.
Pancreatic Cancer Complicated by Pancreatitis Demonstrated on FDG PET/CT.
Clin Nucl Med. 2017; 42(3):239-240 [PubMed] Related Publications
A 73-year-old man was referred for F-FDG PET/CT study for staging of biopsy-proven pancreatic adenocarcinoma. The scan demonstrated focal intense FDG uptake in the pancreatic head, localizing the primary tumor. Additional moderate diffuse uptake was seen throughout the pancreas, suggestive of acute pancreatitis. Concurrent diagnostic CT showed diffuse pancreatic hypoenhancement consistent with edema. Serum lipase level was elevated, confirming a diagnosis of acute pancreatitis.

Jiang L, Nie H, Zhu L, et al.
Adenosquamous Carcinoma of the Pancreas Demonstrated on 18F-FDG PET/CT Imaging.
Clin Nucl Med. 2017; 42(3):206-208 [PubMed] Related Publications
A 69-year-old woman had gradually worsening abdominal discomfort over a year. A pancreatic mass was revealed by abdominal CT. The patient underwent FDG PET/CT for staging, which demonstrated the hypermetabolic pancreatic mass with multiple liver metastases. The lesion was pathologically confirmed as pancreatic adenosquamous carcinoma after biopsy.

Ku YH, Chen SC, Shyr BU, et al.
Pancreatic groove cancer.
Medicine (Baltimore). 2017; 96(2):e5640 [PubMed] Free Access to Full Article Related Publications
Pancreatic groove cancer is very rare and can be indistinguishable from groove pancreatitis. This study is to clarify the characteristics, clinical features, managements, and survival outcomes of this rare tumor.Brief descriptions were made for each case of pancreatic groove cancer encountered at our institute. Individualized data of pancreatic groove cancer cases described in the literature were extracted and added to our database to expand the study sample size for a more complete analysis.A total of 33 patients with pancreatic groove cancer were included for analysis, including 4 cases from our institute. The median tumor size was 2.7 cm. The most common symptom was nausea or vomiting (89%), followed by jaundice (67%). Duodenal stenosis was noted by endoscopy in 96% of patients. The histopathological examination revealed well differentiated tumor in 43%. Perineural invasion was noted in 90%, and lymphovascular invasion and lymph node involvement in 83%. Overall 1-year survival rate was 93.3%, and 3- or 5-year survival rate was 62.2%, with a median survival of 11.0 months. Survival outcome for the well-differentiated tumors was better than those of the moderate/poorly differentiated ones.Early involvement of duodenum causing vomiting is often the initial presentation, but obstructive jaundice does not always happen until the disease progresses. Tumor differentiation is a prognostic factor for survival outcome. The possibility of pancreatic groove cancer should be carefully excluded before making the diagnosis of groove pancreatitis for any questionable case.

Martinez-Useros J, Garcia-Foncillas J
The Role of BRCA2 Mutation Status as Diagnostic, Predictive, and Prognosis Biomarker for Pancreatic Cancer.
Biomed Res Int. 2016; 2016:1869304 [PubMed] Free Access to Full Article Related Publications
Pancreatic cancer is one of the deadliest cancers worldwide, and life expectancy after diagnosis is often short. Most pancreatic tumours appear sporadically and have been highly related to habits such as cigarette smoking, high alcohol intake, high carbohydrate, and sugar consumption. Other observational studies have suggested the association between pancreatic cancer and exposure to arsenic, lead, or cadmium. Aside from these factors, chronic pancreatitis and diabetes have also come to be considered as risk factors for these kinds of tumours. Studies have found that 10% of pancreatic cancer cases arise from an inherited syndrome related to some genetic alterations. One of these alterations includes mutation in BRCA2 gene. BRCA2 mutations impair DNA damage response and homologous recombination by direct regulation of RAD51. In light of these findings that link genetic factors to tumour development, DNA damage agents have been proposed as target therapies for pancreatic cancer patients carrying BRCA2 mutations. Some of these drugs include platinum-based agents and PARP inhibitors. However, the acquired resistance to PARP inhibitors has created a need for new chemotherapeutic strategies to target BRCA2. The present systematic review collects and analyses the role of BRCA2 alterations to be used in early diagnosis of an inherited syndrome associated with familiar cancer and as a prognostic and predictive biomarker for the management of pancreatic cancer patients.

Li J, Sheng S, Zhang K, Liu T
Pain Analysis in Patients with Pancreatic Carcinoma: Irreversible Electroporation versus Cryoablation.
Biomed Res Int. 2016; 2016:2543026 [PubMed] Free Access to Full Article Related Publications
The aim of this article is to evaluate and compare the postprocedure pain in patients with pancreatic carcinoma treated with irreversible electroporation (IRE) and cryoablation (CRYO). We compared 22 patients with 22 lesions in pancreas treated with IRE and 26 patients with 27 lesions treated with cryosurgery. All the patients in the two groups were under celiac plexus block (CPB) treatment to alleviate the postprocedure pain. A numerical rating scale (VAS) consisting of 11-point scales and the 24 h total hydromorphone use were recorded for the analysis of the pain level in the patients who underwent these two technologies separately. Other parameters, such as the complications and the ECOG performance status, were also noted. Statistical analysis was performed by Fisher's exact test, the Chi-square test, and Student's t-test. All the pancreatic carcinoma patients in our study were reported to have postprocedure pain in the two groups. But there was no significant difference in the mean pain score (4.95 (IRE) versus 4.85 (CRYO); P = 0.52) and 24 h total hydromorphone use (3.89 mg (IRE) versus 3.97 mg (CRYO); P = 0.30). IRE is comparable to cryotherapy in the amount of pain that patients with pancreatic carcinoma experience.

Bhagat VH, Sepe T
Pancreatic lymphoma complicating early stage chronic hepatitis C.
BMJ Case Rep. 2017; 2017 [PubMed] Related Publications
Hepatitis C virus (HCV) infection has also been associated with many extrahepatic manifestations including the development of B-cell non-Hodgkin's lymphoma (NHL). Primary pancreatic lymphoma is very rare and comprises 2.2% of NHL and 4.9% of all pancreatic malignancies. Our patient was a woman with a history of infection with HCV found to have a mass in the head of the pancreas. Biopsy of the mass revealed a high-grade B-cell lymphoma consistent with Burkitt's lymphoma. Our case reflects a need to initiate antiviral therapy for all patients infected with HCV even in early stages of fibrosis to prevent cirrhosis and other extrahepatic manifestations of infection with HCV.

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