Cancer of the Pancreas
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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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Information for Patients and the Public
Information for Health Professionals / Researchers
Latest Research Publications
Pancreatic Neuroendocrine Tumours (Islet Cell Tumours)
Familial Pancreatic Cancer

Information Patients and the Public (15 links)

Information for Health Professionals / Researchers (8 links)

Latest Research Publications

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

Mosteiro L, Corominas-Cishek A, Muñiz G, et al.
Ultrasound-guided endoscopic fine needle aspiration cytology in pancreatic lesions: a series of 43 cases with histologic correlation from a single institution.
Anal Quant Cytol Histol. 2014; 36(1):9-14 [PubMed] Related Publications
OBJECTIVE: To describe the usefulness of endoscopic ultrasound-guided fine needle aspiration cytology (EUS-FNAC) in pancreatic lesions.
STUDY DESIGN: During a 5-year period (2007-2011) a total of 391 patients with pancreatic lesions have been studied using EUS-FNAC, with 43 of them having cytohistological correlation with core biopsy or surgical specimens. The diagnostic performance of this technique with and without the pathologist in the endoscopy room has been compared.
RESULTS: On the cytological smears, adenocarcinoma was diagnosed in 13 (30.2%) cases and neuroendocrine neoplasm in 2 (4.6%). Six (13.9%) cases were considered suspicious for malignancy, 2 (4.6%) were solid pseudopapillary tumors, and 20 (46.5%) were negative. There were no mucin-producing cystic neoplasms in the cytological diagnostic approach. After the cytohistological correlation, 23 (53.5%) cases were true positive, 11 (25.5%) were true negative, and 9 (21%) were false negative. There were no false positive cases in the series. Diagnostic precision was 79%, sensitivity 71.18%, specificity 100%, positive predictive value 100%, and negative predictive value 55%. The diagnostic performance of this technique is significantly higher (p < 0.015) when the pathologist is present in the endoscopy room.
CONCLUSION: Our data support the usefulness and reliability of EUS-FNAC in the diagnosis of pancreatic lesions. In our experience, significantly better results are obtained when the pathologist takes an active part in the procedure.

Kawada N, Tanaka S, Uehara H, et al.
Alteration of strain ratio evaluated by transabdominal ultrasound elastography may predict the efficacy of preoperative chemoradiation performed for pancreatic ductal carcinoma: preliminary results.
Hepatogastroenterology. 2014 Mar-Apr; 61(130):480-3 [PubMed] Related Publications
BACKGROUND/AIM: We evaluated the usefulness of ultrasound-elastography (US-elastography) for prediction of therapy effect by measuring strain ratio (SR).
METHODOLOGY: Consecutive patients with resectable pancreatic ductal carcinoma who underwent US-elastography before and after neoadjuvant chemoradiation were included. Patients were classified into either response group or non-response group according to the histological evaluation of resected specimens. Serum carbohydrate antigen 19-9 (CA19-9), SR, and maximum standard uptake value (SUVmax) obtained from 18F-fuluoro-deoxy-D-glucose positron emission tomography and computerized tomography were measured before and after chemoradiation. Alteration rate of each parameter was compared between response group and non-response group.
RESULTS: Seven patients met the inclusion criteria. One patient was excluded from pancreatectomy because liver metastasis was found by laparotomy. Serum CA19-9 was not elevated for 2 patients throughout the chemoradiation. Three patients were classified into response group and the remaining three into non-response group. Alteration rate of CA19-9 and SR was shown to be grater in response group (26.83 +/- 19.69 vs. 4.87 +/- 4.25, and 3.61 +/- 2.40 vs. 1.39 +/- 0.20, respectively), whereas that of SUVmax was not (1.56 +/- 0.43 vs. 2.11 +/- 0.10).
CONCLUSIONS: Increase rate of SR may predict the therapy effect of neoadjuvant chemoradiation for patients with pancreatic ductal carcinoma, especially for patients without elevation of tumor markers.

Cao W, Zhou G, Qiu J, et al.
Research on the epigenetic modification of pancreatic cancer vaccine.
Hepatogastroenterology. 2014 Mar-Apr; 61(130):272-7 [PubMed] Related Publications
Pancreatic cancer is characterized as a type of gastrointestinal tumor with a poor prognosis and high degree of malignancy. CIITA gene was found highly methylated in pancreatic carcinoma cell line PANC-1 and responsible for the low expression of MHC-II that may lead to immune evasion. Here, we tried to prepare pancreatic cancer vaccine with PANC-1 cells via epigenetic modification to enhance the MHC-II expression. Then the vaccine was injected into C57BL/6J mice and the effect was examined. Our study found that the vaccine could promote the proliferation of antigen-specific T cells, enhance the killing activity of cytotoxic lymphocytes (CTL), promote Th1-type cells mediated secretion of cytokines IFN-gamma and IL-2 while inhibiting Th2-type cells mediated secretion of IL-4, and inhibit the secretion of TGF-beta. Generally, the epigenetically modified vaccine could enhance the body's anti-tumor immune response, providing feasibility research on cancer vaccine for therapy of pancreatic cancer.

Related: Cytokines

Kuroki T, Kitasato A, Adachi T, et al.
Single-incision laparoscopic distal pancreatectomy: our initial experience.
Hepatogastroenterology. 2014 Jan-Feb; 61(129):212-4 [PubMed] Related Publications
BACKGROUND/AIMS: Single-incision laparoscopic surgery (SILS) is gaining popularity as a minimally invasive surgery. However, SILS distal pancreatectomy (SILS-DP) remains a challenging surgical procedure. In this study, we describe our initial experience with five cases of SILS-DP.
METHODOLOGY: We present an initial series of SILS-DP, performed between August 2010 and January 2013.
RESULTS: Five patients successfully underwent SILS-DP. The median operative time was 264 min (range, 232-345 min). The median intraoperative blood loss was 71 cc (range, 5-200 cc). All the patients left the hospital in good condition after SILS-DP.
CONCLUSIONS: Although SILS-DP is a safe, feasible, and esthetic procedure, a randomized controlled study is required to determine the advantages of SILS-DP in comparison with the standard laparoscopic method.

Ueda J, Kayashima T, Mori Y, et al.
Hepaticocholecystojejunostomy as effective palliative biliary bypass for unresectable pancreatic cancer.
Hepatogastroenterology. 2014 Jan-Feb; 61(129):197-202 [PubMed] Related Publications
BACKGROUND/AIMS: The majority of patients with pancreatic cancer present with far advanced disease and jaundice. With the advancement of endoscopic interventional techniques, the role of surgical bypass has declined. However, surgical bypass is still considered to be appropriate in patients who are able to tolerate surgery. We performed hepaticocholecystojejunostomy consecutively as a palliative surgical biliary bypass for the purpose of long-term palliation. The aim of this study was to analyze the results of our palliative surgical biliary bypass, hepaticocholecystojejunostomy.
METHODOLOGY: Between January 2001 through December 2009, 69 patients received palliative surgical biliary bypass (bypass group) and 33 patients received endoscopic biliary stenting (stent group) for unresectable pancreatic cancers. Mortality, morbidity and survival between the two groups were compared.
RESULTS: There was no in-hospital death in the bypass group, but 2 patients (6%) in the stent group died in the hospital (p = 0.04). The surgical morbidity rate was 15% in the bypass group, while 20 patients (61%) in the stent group developed complications, mainly due to stent blockage. There was no significant difference in overall survival between the two groups. Among patients who underwent systemic chemotherapy but did not present with jaundice at the time of diagnosis, those who underwent prophylactic surgical biliary bypass before chemotherapy showed better survival than those who underwent systemic chemotherapy preceding biliary bypass or biliary stenting after occurrence of jaundice (p = 0.01).
CONCLUSIONS: Hepaticocholecystojejunostomy resulted in negligible mortality, low morbidity and effective long-term palliation. Prophylactic surgical biliary bypass with gastrointestinal bypass might be a good treatment option for non-jaundiced patients undergoing chemotherapy for unresectable pancreatic cancer.

Bockhorn M, Uzunoglu FG, Adham M, et al.
Borderline resectable pancreatic cancer: a consensus statement by the International Study Group of Pancreatic Surgery (ISGPS).
Surgery. 2014; 155(6):977-88 [PubMed] Related Publications
BACKGROUND: This position statement was developed to expedite a consensus on definition and treatment for borderline resectable pancreatic ductal adenocarcinoma (BRPC) that would have worldwide acceptability.
METHODS: An international panel of pancreatic surgeons from well-established, high-volume centers collaborated on a literature review and development of consensus on issues related to borderline resectable pancreatic cancer.
RESULTS: The International Study Group of Pancreatic Surgery (ISGPS) supports the National Comprehensive Cancer Network criteria for the definition of BRPC. Current evidence supports operative exploration and resection in the case of involvement of the mesentericoportal venous axis; in addition, a new classification of extrahepatic mesentericoportal venous resections is proposed by the ISGPS. Suspicion of arterial involvement should lead to exploration to confirm the imaging-based findings. Formal arterial resections are not recommended; however, in exceptional circumstances, individual therapeutic approaches may be evaluated under experimental protocols. The ISGPS endorses the recommendations for specimen examination and the definition of an R1 resection (tumor within 1 mm from the margin) used by the British Royal College of Pathologists. Standard preoperative diagnostics for BRPC may include: (1) serum levels of CA19-9, because CA19-9 levels predict survival in large retrospective series; and also (2) the modified Glasgow Prognostic Score and the neutrophil/lymphocyte ratio because of the prognostic relevance of the systemic inflammatory response. Various regimens of neoadjuvant therapy are recommended only in the setting of prospective trials at high-volume centers.
CONCLUSION: Current evidence justifies portomesenteric venous resection in patients with BRPC. Basic definitions were identified, that are currently lacking but that are needed to obtain further evidence and improvement for this important patient subgroup. A consensus for each topic is given.

Dimov RS, Kantchev RI, Boev BG, et al.
Laparoscopic resection of the pancreatic tail with preservation of the spleen in a patient with a large pseudopapillary tumor of the pancreas.
Folia Med (Plovdiv). 2014 Jan-Mar; 56(1):56-9 [PubMed] Related Publications
Laparoscopic resections of the pancreas have gained in popularity in the last few years. Those preserving the integrity of the spleen are performed very rarely and are a challenge for every surgeon. We hereby report a case of laparoscopic resection of the pancreatic tail with preservation of the spleen and the integrity and the blood supply to the spleen in a 26 year-old patient with a large pseudopapillary tumor of the pancreas. Postoperative recovery was quick and without complications. The functional and aesthetic result was satisfactory. Laparoscopic resection of the pancreas is a safe and effective therapeutic procedure in selected patients.

Okusaka T, Ikeda M, Fukutomi A, et al.
Safety, tolerability, pharmacokinetics and antitumor activity of ganitumab, an investigational fully human monoclonal antibody to insulin-like growth factor type 1 receptor, combined with gemcitabine as first-line therapy in patients with metastatic pancreatic cancer: a phase 1b study.
Jpn J Clin Oncol. 2014; 44(5):442-7 [PubMed] Related Publications
OBJECTIVE: Previous Phase 1 studies have shown the acceptable safety profile of ganitumab-a fully human monoclonal antibody to insulin-like growth factor Type 1 receptor-in patients with advanced solid tumors. However, ganitumab 20 mg/kg in combination with gemcitabine had not been administered to patients with metastatic pancreatic cancer. To evaluate the safety, tolerability, pharmacokinetics and antitumor activity of ganitumab 20 mg/kg combined with gemcitabine 1000 mg/m(2) as first-line therapy in patients with metastatic pancreatic cancer, we conducted a Phase 1b study.
METHODS: Eligible patients were adults with previously untreated metastatic adenocarcinoma of the pancreas. Patients received gemcitabine 1000 mg/m(2) on Days 1, 8 and 15 plus ganitumab 20 mg/kg on Days 1 and 15 of each 28-day cycle. Gemcitabine was administered intravenously over 30-60 min. Ganitumab was administered intravenously over 60 min after completing gemcitabine infusion.
RESULTS: Six patients were enrolled and received the study treatment. All patients had thrombocytopenia and leukopenia. Other most common adverse events were neutropenia and nausea. One patient had a dose-limiting toxicity defined as Grade 3 neutropenia with fever. Exposure to ganitumab 20 mg/kg was not affected by the administration of gemcitabine. No apparent pharmacokinetic drug-drug interaction was observed. No anti-ganitumab antibodies were detected. Five patients had a measurable tumor region at baseline. Of these, four patients had a best response of stable disease.
CONCLUSIONS: Ganitumab 20 mg/kg combined with gemcitabine 1000 mg/m(2) was tolerable and showed an acceptable safety profile in patients with untreated metastatic pancreatic cancer.

Related: Monoclonal Antibodies IGF1R Gemcitabine

Williamson JM, Finch-Jones M, Pope I
Endoscopic ultrasonography allowing expectant management of pancreatic haemangioma.
Ann R Coll Surg Engl. 2014; 96(3):e1-2 [PubMed] Related Publications
Pancreatic haemangiomas are rare benign tumours that can affect both adults and children. They have an unknown incidence and only 15 adult cases have been reported, all from histological examination. Patients present with vague symptoms relating to tumour mass or they are detected incidentally. Cross-sectional imaging is the mainstay of investigation and may reveal arterially enhancing cystic lesions but in the case presented here, it was non-diagnostic. The use of endoscopic ultrasonography confirmed the nature of the benign lesion, allowing a conservative approach as opposed to operative resection.

He S, Chen CH, Chernichenko N, et al.
GFRα1 released by nerves enhances cancer cell perineural invasion through GDNF-RET signaling.
Proc Natl Acad Sci U S A. 2014; 111(19):E2008-17 [PubMed] Article available free on PMC after 13/11/2014 Related Publications
The ability of cancer cells to invade along nerves is associated with aggressive disease and diminished patient survival rates. Perineural invasion (PNI) may be mediated by nerve secretion of glial cell line-derived neurotrophic factor (GDNF) attracting cancer cell migration through activation of cell surface Ret proto-oncogene (RET) receptors. GDNF family receptor (GFR)α1 acts as coreceptor with RET, with both required for response to GDNF. We demonstrate that GFRα1 released by nerves enhances PNI, even in the absence of cancer cell GFRα1 expression. Cancer cell migration toward GDNF, RET phosphorylation, and MAPK pathway activity are increased with exposure to soluble GFRα1 in a dose-dependent fashion. Dorsal root ganglia (DRG) release soluble GFRα1, which potentiates RET activation and cancer cell migration. In vitro DRG coculture assays of PNI show diminished PNI with DRG from GFRα1(+/-) mice compared with GFRα1(+/+) mice. An in vivo murine model of PNI demonstrates that cancer cells lacking GFRα1 maintain an ability to invade nerves and impair nerve function, whereas those lacking RET lose this ability. A tissue microarray of human pancreatic ductal adenocarcinomas demonstrates wide variance of cancer cell GFRα1 expression, suggesting an alternate source of GFRα1 in PNI. These findings collectively demonstrate that GFRα1 released by nerves enhances PNI through GDNF-RET signaling and that GFRα1 expression by cancer cells enhances but is not required for PNI. These results advance a mechanistic understanding of PNI and implicate the nerve itself as a key facilitator of this adverse cancer cell behavior.

Related: RET

Gundling F, Nerlich A, Heitland W, Schepp W
Neuroendocrine pancreatic carcinoma after initial diagnosis of acute postpartal coeliac disease in a 37-year old woman - fatal coincidence or result of a neglected disease?
Anticancer Res. 2014; 34(5):2449-54 [PubMed] Related Publications
An acute presentation after pregnancy of coeliac disease (CD) in the puerperium is a rare condition which has been described mostly in primigravidae in patients highly suspicious of latent CD. We report the case of a 37-year-old woman who was referred to our Hospital because of refractory watery diarrhea and malnutrition syndrome. Endoscopy of the upper gastrointestinal tract revealed the classic visual features of CD and in addition, some duodenal ulcers negative for Helicobacter pylori, which seems to be another clinical feature in patients with CD. The diagnosis of acute onset of fulminant postpartal CD (Marsh score stage 3c) was confirmed histologically. Remarkably, simultaneous well-differentiated neuroendocrine non-functioning pancreatic neuroendocrine carcinoma (PNET) was diagnosed on radiological abdominal imaging which was performed since serum gastrin was remarkably high, treated by distal pancreatectomy and splenectomy. This report is, to our knowledge, the first description of the two entities, CD and PNET occurring together. Since results of antral histological studies showed diffuse hyperplasia of G-cells, probably in response to hypergastrinaemia, enterochromaffin cell carcinogenesis might have served as a possible link between both diseases.

Iida T, Nakabayashi Y, Okui N, et al.
Successful management of metachronous liver metastasis after pancreaticoduodectomy for pancreatic ductal carcinoma using hepatectomy and chemotherapy: a case report.
Anticancer Res. 2014; 34(5):2417-20 [PubMed] Related Publications
A 63-year-old woman was admitted to our Hospital for treatment of pancreatic head ductal carcinoma, and underwent pancreaticoduodedectomy (PD) in October 2007. At one month after surgery, she received systemic adjuvant chemotherapy using S-1 for three months. Because the serum carbohydrate antigen 19-9 (CA19-9) value was elevated at 23 months after surgery, the patient underwent systemic chemotherapy using gemcitabine. The serum CA19-9 decreased, but abdominal Computed Tomography (CT) revealed a hepatic metastasis in the ventrolateral segment of left hepatic lobe at 28 months after surgery. The chemotherapy was changed to oral S-1. At 35 months after surgery, abdominal CT revealed reduction of liver metastasis and that the serum CA19-9 was normalized, but chemotherapy had to be withdrawn because of severe myelosuppression. Because of her good general condition, the patient underwent partial hepatectomy for the liver metastasis. Histopathological examination demonstrated a complete response. Thirty six months after hepatectomy and 6 years after PD, the patient remains well without recurrence. We herein report a case of successful treatment for metachronous liver metastasis from pancreatic ductal carcinoma after PD by chemotherapy and hepatectomy and review the current literature.

Related: Tegafur-uracil Gemcitabine

Yamamoto Y, Ikoma H, Morimura R, et al.
The clinical impact of the lymph node ratio as a prognostic factor after resection of pancreatic cancer.
Anticancer Res. 2014; 34(5):2389-94 [PubMed] Related Publications
BACKGROUND: The prognostic value of lymph node (LN) status in patients who underwent resection for pancreatic cancer (PC) was examined in the present study.
PATIENTS AND METHODS: Fifty-six patients who underwent macroscopic curative resection for PC were analyzed. Twelve factors, including the number of LN metastases, LN ratio, and N category according to the Japanese Pancreatic Society classification, were analyzed using univariate and multivariate analysis.
RESULTS: The optimal cut-off value was 0.2 for the LN ratio. Positive surgical margins (p=0.022) and LN ratio ≥0.2 (p=0.017) were identified as independent prognostic factors. Among the 33 patients with regional LN metastasis, patients with LN ratio ≥0.2 had significantly worse prognosis than those with LN ratio <0.2 (median survival time 14 vs. 26 months, p=0.048), however, the differences in survival between those with N1 and those with N2 by Japanese Pancreatic Society classification were not statistically significant (p=0.85).
CONCLUSION: The LN ratio might be more useful than other parameters as a predictor for survival after resection of PC.

Sahora K, Schindl M, Kuehrer I, et al.
A phase II trial of two durations of Bevacizumab added to neoadjuvant gemcitabine for borderline and locally advanced pancreatic cancer.
Anticancer Res. 2014; 34(5):2377-84 [PubMed] Related Publications
BACKGROUND: We report the results of a phase II trial of adding the anti-ascular endothelial growth factor (VEGF) bevacizumab to gemcitabine neoadjuvant chemotherapy for patients with borderline and unresectable non-metastatic pancreatic cancer.
PATIENTS AND METHODS: Patients were assigned to one of the two treatment arms. Both groups received 1,000 mg/m(2) gemcitabine on days 1, 8, and 15 of a 4-week cycle for a total of four cycles. Group 1 received 5 mg/kg bevacizumab for six weeks (three doses), every second week, starting at week 6 of gemcitabine therapy. Group 2 received 5 mg/kg bevacizumab for 12 weeks (six doses), every second week, starting at week 1 of gemcitabine therapy. The objective of the present study was to assess the rate of complete radical resection and overall survival.
RESULTS: A total of 30 patients were enrolled: 19 patients had unresectable and 11 patients had borderline-resectable pancreatic cancer. Eleven patients (37%) underwent resection. The median overall survival of patients who underwent tumor resection was 13 months (95% confidence interval=11-15 months).
CONCLUSION: In general, adding bevacizumab to neoadjuvant gemcitabine does not improve outcomes for patients with locally advanced pancreatic cancer. However, in individual cases, surgery is consequently possible and prolonged survival may be observed.

Related: Bevacizumab (Avastin) Gemcitabine

Thorns C, Schurmann C, Gebauer N, et al.
Global microRNA profiling of pancreatic neuroendocrine neoplasias.
Anticancer Res. 2014; 34(5):2249-54 [PubMed] Related Publications
BACKGROUND: Pancreatic neuroendocrine neoplasms (pNEN) are rare tumors with a poor prognosis. Although increasing data have accumulated on the molecular pathology of pNEN, very scarce data exist on microRNAs in pNEN and no data are published on microRNAs as potential biomarkers of pNEN in serum. This study aimed to identify microRNA signatures of pNEN in tissue and serum.
MATERIALS AND METHODS: We included tissue samples from 37 patients with pNEN, 9 patients with non-neoplastic pancreatic pathology, seven samples of micro-dissected pancreatic islets and serum samples of 27 patients with pNEN, as well as of 15 healthy volunteers. MicroRNA expression profiles were established using real-time quantitative Polymerase Chain reaction (PCR) for 754 microRNAs.
RESULTS: MicroRNA signatures differed between pNEN, pancreatic islets and total pancreas, with virtually no overlap between the groups of de-regulated microRNAs. Expression of miR-642 correlated with Ki67 (MiB1) score and miR-210 correlated with metastatic disease. When comparing microRNA levels in serum from patients with pNEN and healthy volunteers, 13 microRNAs were more abundant in the serum of patients. MiR-193b was also up-regulated in pNEN tissue when compared to pancreatic islets and remained significantly increased in serum even when corrected for multiple testing.
CONCLUSION: Evaluation of microRNAs appears to be promising in the assessment of pNEN. In particular, miR-193b, which is also increased in serum, may be a potential new biomarker of pNEN.

Rijkers AP, Valkema R, Duivenvoorden HJ, van Eijck CH
Usefulness of F-18-fluorodeoxyglucose positron emission tomography to confirm suspected pancreatic cancer: a meta-analysis.
Eur J Surg Oncol. 2014; 40(7):794-804 [PubMed] Related Publications
INTRODUCTION: Pancreatic cancer is among the five most lethal malignancies in the world. Unfortunately, many malignant tumors go undetected by the current primary diagnostic tools. (18)FDG-PET and (18)FDG-PET/CT might be useful to confirm suspected pancreatic cancer.
METHODS: A meta-analysis was performed using all major search engines. Methodological quality of included studies was assessed as well as quality of the PET-protocol. The following pooled estimates served as primary outcome measures: sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy.
RESULTS: Thirty-five studies were included. Pooled estimates for (18)FDG-PET were: sensitivity 90%, specificity 76%, PPV 90%, NPV 76% and accuracy 86%. Pooled estimates for (18)FDG-PET/CT were: sensitivity 90%, specificity 76%, PPV 89%, NPV 78% and accuracy 86%. The pooled sensitivity and specificity for (18)FDG-PET to differentiate between pancreatic cancer and chronic pancreatitis were 90% and 84%, respectively.
CONCLUSION: Both (18)FDG-PET and (18)FDG-PET/CT offer no benefit over the current primary diagnostic tools in diagnosing pancreatic cancer. However, the (18)FDG-PET/CT systems are still improving. We should investigate the sensitivity and specificity of these new systems while reevaluating the tradeoff between false positive and false negative results. Yet, (18)FDG-PET/CT may have a role in the staging of pancreatic cancer, in survival prediction, and may add to other diagnostic information, like histology.

Westerhoff M, Tretiakova M, Hart J, et al.
The expression of FOXL2 in pancreatic, hepatobiliary, and renal tumors with ovarian-type stroma.
Hum Pathol. 2014; 45(5):1010-4 [PubMed] Related Publications
FOXL2, a gene encoding a member of the fork-head-winged-helix family of transcription factors, is one of the earliest expressed genes during female gonadal development. It is expressed in normal ovarian stroma and ovarian neoplasms with granulosa cell lineage. Nonovarian tumors such as pancreatic mucinous cystic neoplasms (PMCs), hepatobiliary cystadenomas (HBCs), and mixed epithelial and stromal tumor of the kidney (MEST) have ovarian-type stroma. Immunohistochemical staining with FOXL2, estrogen receptor, and progesterone receptor was performed on 21 PMCs, 13 HBCs, and 10 MESTs and assessed for nuclear immunohistochemical positivity in the tumor stroma. All cases of PMC and HBC demonstrated nuclear reactivity for FOXL2 in the subepithelial stromal cells. Ninety percent of MEST demonstrated nuclear FOXL2 positivity. Estrogen receptor nuclear positivity was demonstrated in 57% of PMC, 77% of HBC, and 80% of MEST. Progesterone receptor nuclear positivity was present in 67% of PMC, 100% of HBC, and 90% of MEST. Clinical information was available for 37 patients. Seventy-eight percent of the patients had a history of obesity, heavy alcohol use, or hormone-related therapy. The 2 male patients had histories significant for morbid obesity and chronic alcoholism. FOXL2 is expressed from the early stages of ovarian development and has been shown to be mandatory for normal ovarian function. We have shown that it is also expressed in the aberrant ovarian-type stroma characteristic of PMC, HBC, and MEST. Most of such patients, including the rare male patients, have risk factors for hormonal abnormalities such as obesity and hormonal replacement therapy.

Related: Extra-Hepatic Bile duct cancer (cholangiocarcinoma) Kidney Cancer Liver Cancer

Goudard Y, Gaujoux S, Dokmak S, et al.
Reappraisal of central pancreatectomy a 12-year single-center experience.
JAMA Surg. 2014; 149(4):356-63 [PubMed] Related Publications
IMPORTANCE: Central pancreatectomy, as an alternative to standard resection for benign and low-grade pancreatic neoplasms, has been described in mainly small retrospective series.
OBJECTIVE: To describe a large single-center experience with central pancreatectomy.
DESIGN, SETTING, AND PARTICIPANTS: A retrospective case series in a tertiary referral center included 100 consecutive patients undergoing central pancreatectomy with pancreaticogastrostomy from January 1, 2000, to March 1, 2012.
MAIN OUTCOMES AND MEASURES: Surgical indications, postoperative morbidity, mortality, and long-term outcomes regarding pancreatic function and recurrence.
RESULTS: Central pancreatectomies were performed mainly for neuroendocrine tumors (35%), intraductal papillary mucinous neoplasms (33%), solid pseudopapillary neoplasms(12%), and mucinous cystadenomas (6%). The postoperative mortality rate was 3% (due to pulmonary embolisms in 2 patients and hemorrhage after pancreatic fistula in 1 patient). Clavien-Dindo III or IV complications occurred in 15%of patients and were due mainly to pancreatic fistula, requiring 10 radiologic drainage procedures, 7 endoscopic procedures, and 6 reoperations overall. After a median follow-up of 36 months, the rates of new-onset exocrine and endocrine insufficiency were 6%and 2%, respectively. Overall, 7 lesions could be considered undertreated, including 3 node-negative R0 microinvasive intraductal papillary mucinous neoplasms (without recurrence at 27, 29, and 34 months) and 4 node-positive neuroendocrine tumors (with 1 hepatic recurrence at 66 months). Among the 25 patients with a doubtful preoperative diagnosis, 9 could be considered over treated (ie, operated on for benign non evolutive asymptomatic lesions).
CONCLUSIONS AND RELEVANCE: Central pancreatectomy is associated with an excellent pancreatic function at the expense of a significant morbidity and a non-nil mortality rate,underestimated by the published literature. The procedure is best indicated for benign or low-grade lesions in young and fit patients who can sustain a significant postoperative morbidity and could benefit from the excellent long-term results.

Related: France

Steponkiene S, Valanciunaite J, Skripka A, Rotomskis R
Cellular uptake and photosensitizing properties of quantum dot-chlorin e6 complex: in vitro study.
J Biomed Nanotechnol. 2014; 10(4):679-86 [PubMed] Related Publications
Recently it has been suggested that quantum dots could be used in the photodynamic therapy of cancer as resonant energy donors for conventional porphyrin type photosensitizers. Here we summarize our results obtained by studying a non-covalent complex formed between quantum dots and a second generation photosensitizer, chlorin e6, in aqueous medium and in live pancreatic MiaPaCa2 cancer cells. Spectral changes in the absorption and photoluminescence of quantum dots and chlorin e6, as well as changes in the photoluminescence lifetime of quantum dots, revealed the formation of quantum dot-chlorin e6 complex. Fluorescence confocal microscopy with spectral imaging unit showed uptake of quantum dot-chlorin e6 complex in live cancer cells: the complex localized in plasma membrane and endocytic vesicles. Fluorescence lifetime imaging revealed Forster resonance energy transfer from quantum dots to chlorin e6 within live cells. Finally, a light-induced damage to cancer cells by the quantum dot-chlorin e6 complex was achieved.

Related: Apoptosis

De Angelis C, Manfrè SF, Pellicano R
Endoscopic ultrasonography for diagnosis and staging of pancreatic adenocarcinoma: key messages for clinicians.
Minerva Med. 2014; 105(2):121-8 [PubMed] Related Publications
Endoscopic ultrasound (EUS) is a technique that combines the potential of endoscopy, which enables the visual examination of the mucosal surface of any gastrointestinal (GI) tract, with ultrasonography. Despite diagnostic and therapeutic advance, pancreatic cancer (PC), in particular ductal adenocarcinoma, remains the most deadly of all GI malignancies, with a 5-years survival rate less than 1.8%. Moreover its incidence appears to be increasing and most patients present with advanced cancer either locally or with metastatic spread. Thus, all efforts must be oriented towards the need of an early diagnosis and to reliably identify patients who really can benefit from major surgical interventions. To date the most accurate imaging techniques for PC diagnosis and staging remain contrast-enhanced computed tomography and EUS. While the former should be the first choice in patients with suspected PC, EUS has the highest accuracy in detecting small lesions, in assessing tumor size and lymph nodes involvement. The possibility to obtain samples from suspicious lesions or lymph nodes, by means of EUS-guided fine-needle aspiration, makes this procedure an ideal staging modality for PC. Since an accurate preoperative evaluation is essential to choose the correct management strategy, EUS role is crucial.

Van Heek NT, Busch OR, Van Gulik TM, Gouma DJ
Preoperative biliary drainage for pancreatic cancer.
Minerva Med. 2014; 105(2):99-107 [PubMed] Related Publications
This review is to summarize the current knowledge about preoperative biliary drainage (PBD) in patients with biliary obstruction caused by pancreatic cancer. Most patients with pancreatic carcinoma (85%) will present with obstructive jaundice. The presence of toxic substances as bilirubin and bile salts, impaired liver function and altered nutritional status due to obstructive jaundice have been characterized as factors for development of complications after surgery. Whereas PBD was to yield beneficial effects in the experimental setting, conflicting results have been observed in clinical studies. The meta-analysis from relative older studies as well as more importantly a recent clinical trial showed that PBD should not be performed routinely. PBD for patients with a distal biliary obstruction is leading to more serious complications compared with early surgery. Arguments for PBD have shifted from a potential therapeutic benefit towards a logistic problem such as patients suffering from cholangitis and severe jaundice at admission or patients who need extra diagnostic tests, or delay in surgery due to a referral pattern or waiting list for surgery as well as candidates for neoadjuvant chemo(radio)therapy. If drainage is indicated in these patients it should be performed with a metal stent to reduce complications after the drainage procedure such as stent occlusion and cholangitis. Considering a change towards more neoadjuvant therapy regimes improvement of the quality of the biliary drainage concept is still important.

Gill RM, Michael A, Westley L, et al.
SULF1/SULF2 splice variants differentially regulate pancreatic tumour growth progression.
Exp Cell Res. 2014; 324(2):157-71 [PubMed] Related Publications
This study highlights the highly dynamic nature of SULF1/SULF2 splice variants in different human pancreatic cancers that regulate the activities of multiple cell signalling pathways in development and disease. Most pancreatic tumours expressed variable levels of both SULF1 and SULF2 variants including some expression during inflammation and pancreatitis. Many ductal and centro-acinar cell-derived pancreatic tumours are known to evolve into lethal pancreatic ductal adenocarcinomas but the present study also detected different stages of such tumour progression in the same tissue biopsies of not only acinar cell origin but also islet cell-derived cancers. The examination of caerulein-induced pancreatic injury and tumorigenesis in a Kras-driven mouse model confirmed the activation and gradual increase of SULF1/SULF2 variants during pancreatitis and tumorigenesis but with reduced levels in Stat3 conditional knockout mice with reduced inflammation. The significance of differential spatial and temporal patterns of specific SULF1/SULF2 splice variant expression during cancer growth became further apparent from their differential stimulatory or inhibitory effects on growth factor activities, tumour growth and angiogenesis not only during in vitro but also in vivo growth thus providing possible novel therapeutic targets.

Zhu Y, Karakhanova S, Huang X, et al.
Influence of interferon-α on the expression of the cancer stem cell markers in pancreatic carcinoma cells.
Exp Cell Res. 2014; 324(2):146-56 [PubMed] Related Publications
The cytokine interferon-α (IFNα) belongs to the group of type I interferons already used in cancer therapy. This drug possesses radio- and chemo-sensitizing, and shows anti-angiogenic properties. Cancer stem cells (CSC) are a unique population of tumor cells that initiate secondary tumors, and are responsible for metastasis formation. Patients with pancreatic ductal adenocarcinoma (PDAC) have an especially poor prognosis, with 5-year survival rates of only ~1% and median survival of 4-6 months. PDAC is characterized by the presence of CSC. In this work we demonstrate for the first time that IFNα up-regulates the expression of the CSC markers CD24, CD44 and CD133 in in vitro and in vivo models of PDAC. We showed the IFNα effects on the migration and invasion of PDAC cells, which is associated with the level of the CSC marker expression. In vivo, this drug inhibits tumor growth but promotes metastasis formation in the early stage of tumor growth. We propose that IFNα may enhance the enrichment of CSC in PDAC tumors. Additionally we also suggest that in combination therapy of solid tumors with IFNα, this drug should be given to patients prior to chemotherapy to achieve the CSC activation.

Berger NA
Obesity and cancer pathogenesis.
Ann N Y Acad Sci. 2014; 1311:57-76 [PubMed] Related Publications
Overweight and obesity have reached pandemic levels on a worldwide basis and are associated with increased risk and worse prognosis for many but not all malignancies. Pathophysiologic processes that affect this association are reviewed, with a focus on the relationship between type 2 diabetes mellitus and cancer, lessons learned from the use of murine models to study the association, the impact of obesity on pancreatic cancer, the effects of dietary fats and cholesterol on cancer promotion, and the mechanisms by which the intestinal microbiome affects obesity and cancer.

de Herder WW
GEP-NETS update: functional localisation and scintigraphy in neuroendocrine tumours of the gastrointestinal tract and pancreas (GEP-NETs).
Eur J Endocrinol. 2014; 170(5):R173-83 [PubMed] Related Publications
For patients with neuroendocrine tumours (NETs) of the gastrointestinal tract and pancreas (GEP) (GEP-NETs), excellent care should ideally be provided by a multidisciplinary team of skilled health care professionals. In these patients, a combination of nuclear medicine imaging and conventional radiological imaging techniques is usually mandatory for primary tumour visualisation, tumour staging and evaluation of treatment. In specific cases, as in patients with occult insulinomas, sampling procedures can provide a clue as to where to localise the insulin-hypersecreting pancreatic NETs. Recent developments in these fields have led to an increase in the detection rate of primary GEP-NETs and their metastatic deposits. Radiopharmaceuticals targeted at specific tumour cell properties and processes can be used to provide sensitive and specific whole-body imaging. Functional imaging also allows for patient selection for receptor-based therapies and prediction of the efficacy of such therapies. Positron emission tomography/computed tomography (CT) and single-photon emission CT/CT are used to map functional images with anatomical localisations. As a result, tumour imaging and tumour follow-up strategies can be optimised for every individual GEP-NET patient. In some cases, functional imaging might give indications with regard to future tumour behaviour and prognosis.

Related: Gastrointestinal System Cancers

Cecka F, Jon B, Subrt Z, Ferko A
Solid pseudopapillary tumour of the pancreas: diagnosis, treatment, and prognosis.
Acta Chir Belg. 2014 Jan-Feb; 114(1):58-62 [PubMed] Related Publications
BACKGROUND: Solid pseudopapillary tumour (SPT) of the pancreas is a relatively rare entity which most commonly occurs in young women. In this paper we report our clinical experience together with the current knowledge on the diagnostics, treatment and prognosis of this rare tumour.
METHODS: We reviewed hospital records of patients diagnosed with a solid pseudopapillary tumour of the pancreas between January 2002 and December 2011 at the Department of Surgery, University Hospital Hradec Králové, Czech Republic. Clinical, operative, pathological data were obtained on all the patients.
RESULTS: Over the 10-year period of the study we performed 181 planned pancreatic resections in our department. Overall, the 30-day postoperative mortality rate in this series of patients was 2.2%. SPT was diagnosed in 4 cases. All the patients were women and the average age was 34 years. Preoperative endosonography with biopsy sample was performed in all the patients and the diagnosis of SPT was known in all the patients before the surgical procedure.
CONCLUSIONS: The current knowledge of SPT is based only on case reports and small series. It typically occurs in young women and therefore the presence of a large pancreatic mass in a young woman may suggest a diagnosis of SPT. SPT has a low malignant potential and the prognosis is excellent following complete surgical resection in the majority of the cases.

Guo Q, Wu Y
Surgical treatment of pancreatic islet cell tumor: report of 44 cases.
Hepatogastroenterology. 2013 Nov-Dec; 60(128):2099-102 [PubMed] Related Publications
BACKGROUND/AIMS: Open approach was the conventional ways for surgical treatment of pancreatic islet cell tumor. The study was to report the outcome of open approach with pancreatic islet cell tumor in a single institution in China.
METHODOLOGY: Forty-four consecutive pancreatic islet cell tumor patients who underwent surgical treatment were retrospectively analyzed.
RESULTS: There were 16 pancreatic nonfunctioning islet cell tumor (PNIT) patients and 28 functioning islet cell tumor patients which were insulinoma. Seventeen PNIT were found and larger than media size of thirty-nine insulinoma (4.53 +/- 2.67 vs. 1.87 +/- 0.86, p < 0.05) in diameter. The size of malignant and benign PNIT has a significant difference (6.33 +/- 2.06 vs. 3.45 +/- 2.51, p < 0.05 ), but not in insulinoma. Among PNIT, distal pancreatectomy plus splenectomy were required in 8 patients, while segmental pancreatectomy was performed in 3 cases. In addition, 1 and 4 patients received pancreatoduodenectomy and tumor enucleation respectively. Seventeen insulinomas patients (60.7%) underwent enucleation, and 2 patients (7.1%) underwent distal pancreatectomy with splenectomy. Segmental pancreatectomy, pancreatoduodenectomy and distal pancreatectomy preserving spleen was performed in 2, 4 and 3 cases respectively. The percentage was zero in-hospital death. The morbidity was 6.2% (1/16) for PNIT and 28.6% (8/28) for insulinomas.
CONCLUSIONS: Open surgery remains a nice way in the management of pancreatic islet cell tumor at least in our institution.

Shimoda M, Mori S, Kita J, et al.
Results of pancreaticoduodenectomy with portal or superior mesenteric vein resection for locally advanced pancreatic head cancer.
Hepatogastroenterology. 2013 Nov-Dec; 60(128):2094-8 [PubMed] Related Publications
BACKGROUND/AIMS: It is known that portal vein (PV) or superior mesenteric vein (SMV) is easily invaded by locally advanced pancreatic head cancer due to anatomical characteristics. Few studies have investigated the results of PD with PV or SMV resection (PVR) for pancreatic head cancer.
METHODOLOGY: We retrospectively reviewed a database of 83 patients who had undergone PD for pancreatic head cancer (PC). We divided them into two groups, a group with PD and PVR (PD +PVR G) and a group with PD and no PVR (PD -PVR G). The clinicopathological findings and mortality were analyzed.
RESULTS: Twenty-nine of the 83 patients (34.9%) needed PD with PVR. Median survival and disease free survival were 20.4 months and 10.6 months, respectively. The 5-year overall survival rate was 8.1% in PD +PVR G and 7.4% in PD -PVR G, respectively. There was no difference between the two groups (p = 0.091, HR: 1.576; 95% CI: 0.9299-2.670). The 5-year disease free survival rate was 9.6% in PD +PVR G and 10.2% in PD -PVR G, respectively. Also, there was no difference between the two groups (p = 0.206, HR: 1.414; 95% CI: 0.8264-2.420).
CONCLUSIONS: Since PVR by itself is not a risk factor of postoperative morbidity and mortality and contributes to improving 5-year overall survival and disease free survival, PVR should be done for selected cases with locally advanced pancreas head cancer.

Unek T, Unek IT, Agalar AA, et al.
CD40 expression in pancreatic cancer.
Hepatogastroenterology. 2013 Nov-Dec; 60(128):2085-93 [PubMed] Related Publications
BACKGROUND: CD40, a tumor necrosis factor receptor family member, is expressed in a variety of cell types. This widespread expression suggests that CD40 may play an important role in normal physiology and disease pathogenesis. The objective of the current study was to investigate the expression of CD40, and its association with clinicopathological features and survival in patients with pancreatic ductal adenocarcinoma.
METHODOLOGY: CD40 expression was assessed in 53 pancreatic ductal adenocarcinoma surgical specimens by immunohistochemistry, and expression was correlated with patient clinicopathological parameters and outcome.
RESULTS: Among 53 pancreatic cancer specimens, CD40 expression was detected in 13 specimens (24.5%), and peritumoral lymphocytes were present in 45 specimens (84.9%). Patients with CD40-positive tumors exhibited prolonged median disease-free survival (DFS) compared with patients with CD40-negative tumors (15.60 +/- 3.87 versus 10.03 +/- 1.92); however, this was not significant (p = 0.845). Patients with peritumoral lymphocytic reaction exhibited prolonged median DFS compared with patients without peritumoral lymphocytes (10.96 +/- 1.40 vs. 7.60 +/- 0.47); however, this was not significant (p = 0.624). Patients with peritumoral lymphocytic reaction exhibited higher median overall survival compared with patients without peritumoral lymphocytes (15.20 +/- 1.78 vs. 10.13 +/- 1.39); however, again this was not significant (p = 0.100).
CONCLUSIONS: These results suggest that CD40 expression on pancreatic cancer cells and peritumoral lymphocytic reaction may serve as prognostic markers.

Related: CD40 molecule, TNF receptor superfamily member 5

Jiang Y, Liu M, Li Z, Jiang Y
Discovery of novel candidate oncogenes in pancreatic carcinoma using high-throughput microarrays.
Hepatogastroenterology. 2013 Nov-Dec; 60(128):1825-32 [PubMed] Related Publications
BACKGROUND/AIMS: Pancreatic cancer is one of the most aggressive tumors in mankind. Its aggressiveness is only due to the biological progressive characteristics but also the difficulty for clinical early detection which urges us to find diagnostic tools for early diagnosis. Biomarkers are a developing tool used to measure molecules such as proteins, DNA, or RNAs in blood samples or suspected tumor tissues. The molecular dysregulation is believed to play major roles in tumorigenesis or a result after the tumor formation and can be used as a biomarker for tumor detection.
METHODOLOGY: In this paper, we studied the gene expression profiles using tissues from pancreatic cancer patients.
RESULTS: We observed dysregulation of gene expression profiles using high-throughput sequencing technique and verified three-gene upregulation, REG4, CDH3 and S100P both in pancreatic cell lines and carcinoma tissues by RT-PCR and Northern Blot. A detailed description of the genes involved is listed within this article.
CONCLUSIONS: We believe that by unraveling the gene dysregulation profiles in pancreatic tumor tissues can we achieve an early and precise diagnosis of pancreatic cancer. Moreover, these newly found genes, due to their functions involved in cell migration and mitosis, may play major roles in tumorigensis.

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