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).

Macin G, Hekimoglu K, Uner H, Tarhan C
Pancreatic cystic lymphangioma: diagnostic approach with MDCT and MR imaging.
JBR-BTR. 2014 Mar-Apr; 97(2):97-9 [PubMed] Related Publications
Lymphangiomas are rare congenital benign tumors arising from the lymphatic system mostly encountered in the neck and axillary regions of pediatric patients. Pancreatic cystic lymphangiomas very rarely occur in adults. Radiologically, the lesion may mimic pancreatic carcinoma and should be considered in the differential diagnosis of any patient found to have an abdominal cystic mass. In this article, we present a 50-year-old man who presented with pain in the upper abdomen, nausea, and abdominal swelling. On computed tomography (CT) and magnetic resonance (MR) imaging, a gross septated cystic lesion was detected in the upper abdomen which extended from the pancreatic corpus to the left liver lobe. The patient underwent complete resection of tumor. Pathology revealed a cystic lymphangioma.


Collin M, Honoré P, De Roover A, Meurisse M
Solid pseudopapillary tumor of the pancreas: a report of six cases.
Acta Chir Belg. 2014 Mar-Apr; 114(2):110-4 [PubMed] Related Publications
BACKGROUND: Solid pseudopapillary tumor of the pancreas (SPTP) is a rare pancreatic neoplasm. The aim of this study was to discuss the clinical presentation, management, and outcome of patients with this kind of tumor.
MATERIALS AND METHODS: A retrospective review was performed in 6 patients with SPTP surgically treated between January 2004 and September 2011 in our hospital.
RESULTS: All the 6 patients were female. The mean age of the patients was 39 years (range, 18 to 67 years). The main clinical presentation was abdominal pain or discomfort, however a third of the patients were asymptomatic. The mean size of the tumor was 9.7 cm (range, 2.5 to 18 cm). Three tumors had a well defined capsule, 3 tumors extended in the pancreas. Four of the 6 tumors had a cystic component, and calcifications were observed in one tumor. No lymph node involvement, no lymphatic invasion and no nerve invasion were observed. One tumor showed an infiltration of the splenic vein, and another patient had a liver metastasis with complete resection. Distal pancreatectomy (n = 3), local resection (n = 1), cephalic duodenopancreatectomy (n = 1), and distal pancreatectomy associated with a right hepatectomy (n = 1) were performed. The main postoperative complication in the short-term was bleeding (n = 1), and long-term the development of an insulin-requiring diabetes (n = 2). No patient received adjuvant therapy. Overall mortality rate was 0%. All patients were still alive without recurrent disease with a median follow up of 36.2 months.
CONCLUSION: Patients with SPTP have an excellent prognosis after its complete removal, even if it is a minimized resection.


Caplin ME, Pavel M, Ćwikła JB, et al.
Lanreotide in metastatic enteropancreatic neuroendocrine tumors.
N Engl J Med. 2014; 371(3):224-33 [PubMed] Related Publications
BACKGROUND: Somatostatin analogues are commonly used to treat symptoms associated with hormone hypersecretion in neuroendocrine tumors; however, data on their antitumor effects are limited.
METHODS: We conducted a randomized, double-blind, placebo-controlled, multinational study of the somatostatin analogue lanreotide in patients with advanced, well-differentiated or moderately differentiated, nonfunctioning, somatostatin receptor-positive neuroendocrine tumors of grade 1 or 2 (a tumor proliferation index [on staining for the Ki-67 antigen] of <10%) and documented disease-progression status. The tumors originated in the pancreas, midgut, or hindgut or were of unknown origin. Patients were randomly assigned to receive an extended-release aqueous-gel formulation of lanreotide (Autogel [known in the United States as Depot], Ipsen) at a dose of 120 mg (101 patients) or placebo (103 patients) once every 28 days for 96 weeks. The primary end point was progression-free survival, defined as the time to disease progression (according to the Response Evaluation Criteria in Solid Tumors, version 1.0) or death. Secondary end points included overall survival, quality of life (assessed with the European Organization for Research and Treatment of Cancer questionnaires QLQ-C30 and QLQ-GI.NET21), and safety.
RESULTS: Most patients (96%) had no tumor progression in the 3 to 6 months before randomization, and 33% had hepatic tumor volumes greater than 25%. Lanreotide, as compared with placebo, was associated with significantly prolonged progression-free survival (median not reached vs. median of 18.0 months, P<0.001 by the stratified log-rank test; hazard ratio for progression or death, 0.47; 95% confidence interval [CI], 0.30 to 0.73). The estimated rates of progression-free survival at 24 months were 65.1% (95% CI, 54.0 to 74.1) in the lanreotide group and 33.0% (95% CI, 23.0 to 43.3) in the placebo group. The therapeutic effect in predefined subgroups was generally consistent with that in the overall population, with the exception of small subgroups in which confidence intervals were wide. There were no significant between-group differences in quality of life or overall survival. The most common treatment-related adverse event was diarrhea (in 26% of the patients in the lanreotide group and 9% of those in the placebo group).
CONCLUSIONS: Lanreotide was associated with significantly prolonged progression-free survival among patients with metastatic enteropancreatic neuroendocrine tumors of grade 1 or 2 (Ki-67 <10%). (Funded by Ipsen; CLARINET ClinicalTrials.gov number, NCT00353496; EudraCT 2005-004904-35.).

Related: Gastrointestinal System Cancers


Karamitopoulou E, Shoni M, Theoharides TC
Increased number of non-degranulated mast cells in pancreatic ductal adenocarcinoma but not in acute pancreatitis.
Int J Immunopathol Pharmacol. 2014 Apr-Jun; 27(2):213-20 [PubMed] Related Publications
Increasing evidence indicates that tumor microenvironment (TME) is crucial in tumor survival and metastases. Inflammatory cells accumulate around tumors and strangely appear to be permissive to their growth. One key stroma cell is the mast cell (MC), which can secrete numerous pro- and antitumor molecules. We investigated the presence and degranulation state of MC in pancreatic ductal adenocarcinoma (PDAC) as compared to acute ancreatitis (AP). Three different detection methods: (a) toluidine blue staining, as well as immunohistochemistry for (b) tryptase and (c) c-kit, were utilized to assess the number and extent of degranulation of MC in PDAC tissue (n=7), uninvolved pancreatic tissue derived from tumor-free margins (n=7) and tissue form AP (n=4). The number of MC detected with all three methods was significantly increased in PDAC, as compared to normal pancreatic tissue derived from tumor-free margins (p<0.05). The highest number of MC was identified by c-kit, 22.2∓7.5 per high power field (HPF) in PDAC vs 9.7∓5.1 per HPF in normal tissue. Contrary to MC in AP, where most of the detected MC were found degranulated, MC in PDAC appeared intact. In conclusion, MC are increased in number, but not degranulated in PDAC, suggesting that they may contribute to cancer growth by permitting selective release of pro-tumorogenic molecules.


Tanţău A, Negrean V, Alexescu T, et al.
Two different types of diabetes mellitus in pancreatic cancer population. Comparative study between new onset and long standing diabetes mellitus on 76 patients with pancreatic cancer.
Rom J Intern Med. 2014 Jan-Mar; 52(1):18-23 [PubMed] Related Publications
BACKGROUND: There are some studies which have reported a higher diagnosis probability for PC if the DM occurred within the past 2-3 years. Information on the clinical profile of pancreatic cancer (PC) associated with diabetes mellitus (DM) is limited. The aim of the study was to compare clinic-morphological features in patients with new onset DM and PC and long lasting DM and PC, in order to detect new factors or markers which can help in early diagnosis of PC.
METHODS: This study included 76 patients with pancreatic cancer admitted between 2000-2009 in the 4th Medical Clinic Cluj-Napoca; in group A 56 patients with PC and new onset of DM (< 24 months duration) were included and in group B 20 patients with PC and long standing diabetes (> 60 months duration) were included. We compared the demographic, clinical, biochemical and morphological characteristics of new onset or long lasting DM and pancreatic cancer.
RESULTS: New onset DM was more prevalent (74% vs. 26%, p < .05) than long lasting DM among patients with PC. The patients with long lasting DM had a greater frequency of urban environment (100% vs. 55.6% p = .02), a higher body mass index (BMI)(32.1 SD 8.4 vs. 29.9 SD 6.7 kg/m2, p = .05), higher fasting blood glucose levels (182 mg/dL vs. 134 mg/dL, p = .008) and urinary ketone bodies (60% vs. 10.7%, p = .002) compared with those with new-onset DM and PC. There was no statistical difference regarding gender, median age, blood group, location and staging of tumours, long and hard alcohol and cigarettes consumption, between group A and B.
CONCLUSIONS: New onset DM was more significantly frequent than long lasting DM in patients with PC. New onset diabetes DM associated with PC is frequent, mild and non-decompensated. In patients with PC and long lasting DM, the metabolic status and diabetes are imbalanced.


Rades D, Huttenlocher S, Schild SE, Bartscht T
Metastatic spinal cord compression from pancreatic cancer.
Anticancer Res. 2014; 34(7):3727-30 [PubMed] Related Publications
BACKGROUND/AIM: Pancreatic cancer is an extremely rare entity in patients with metastatic epidural spinal cord compression (MESCC). This study aimed to identify prognostic factors for functional outcome and survival following irradiation.
PATIENTS AND METHODS: Ten variables were investigated in 15 patients: age, gender, performance score, time from diagnosis of pancreatic cancer to MESCC, number of involved vertebrae, ambulatory status, bone metastases, organ metastases, time developing motor deficits, and the radiation schedule (1×8 Gy vs. fractionated radiotherapy schedules).
RESULTS: Better post-treatment motor function was significantly associated with absence of organ metastases (p=0.025). Better survival was also significantly associated with absence of organ metastases: 6-month survival rates were 100% and 9%, respectively (p=0.006). The radiation schedule had no significant impact on treatment outcomes.
CONCLUSION: Patients with organ metastases have a very limited life expectancy and are good candidates for irradiation with 1×8 Gy instead of fractionated schedules.


Yang MH, Kim HT, Lee KT, et al.
KML001 inhibits cell proliferation and invasion in pancreatic cancer cells through suppression of NF-κB and VEGF-C.
Anticancer Res. 2014; 34(7):3469-74 [PubMed] Related Publications
Pancreatic cancer is an aggressive malignancy with poor prognosis and the efficacy of chemotherapy is limited. KML001 (sodium meta-arsenite) has been demonstrated to have anticancer activity against some solid cancer cells. The aim of the present study was to determine the effect of KML001 on cell proliferation, migration, and invasion of pancreatic cancer cells. The Dojindo Cell Counting Kit-8 assay was used to determine the inhibition of pancreatic cancer cell proliferation by drugs. Cell migration and invasion were examined using 24-well inserts and Matrigel™-coated invasion chambers. The activity of nuclear factor-kappa B (NF-κB) p65, vascular endothelial growth factor-C (VEGF-C), and matrix metalloproteinase-9 (MMP-9) were measured by enzyme-linked immunosorbent assay (ELISA). KML001 inhibited the proliferation of pancreatic cancer cells in a dose- and time-dependent manner. KML001 also inhibited the migration and invasion of pancreatic cancer cells in a dose-dependent manner. KML001 significantly decreased NF-κB p65 and VEGF-C activities in the pancreatic cancer cells. KML001 inhibited cell proliferation, migration, and invasion in pancreatic cancer cells. Suppression of NF-κB and VEGF-C activation may partly be associated with the anticancer activity of KML001. These results suggest that KML001 could be a novel potential therapeutic agent for treatment of pancreatic cancer.

Related: VEGFC


Sugimoto K, Shimada M, Utsunomiya T, et al.
Valproic acid enhances the anti-tumor effect of pegylated interferon-α towards pancreatic cancer cell lines.
Anticancer Res. 2014; 34(7):3403-9 [PubMed] Related Publications
BACKGROUND: Valproic acid (VPA) acts as a specific inhibitor of class I HDACs and it use has been proven to be safe since a long time.
MATERIALS AND METHODS: In the present study, we investigated the effect of VPA in the combination with pegylated interferon-α (PEG-IFNα) in inhibition of cell proliferation of human pancreatic cancer cell lines.
RESULTS: VPA enhanced the effect of PEG-IFNα, and the effect was decreased by the caspase inhibitor. VPA alone and VPA in combination with PEG-IFNα increased the expression of interferon-α receptor and interferon regulatory factor 8.
CONCLUSION: The combination of VPA and PEG-IFNα can be useful for the treatment of pancreatic cancer.


Ma C, Nong K, Wu B, et al.
miR-212 promotes pancreatic cancer cell growth and invasion by targeting the hedgehog signaling pathway receptor patched-1.
J Exp Clin Cancer Res. 2014; 33:54 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: microRNAs (miRNAs) are a class of small non-coding RNAs that play important roles in carcinogenesis. In the present study, we investigated the effect of miR-212 on pancreatic ductal adenocarcinoma (PDAC) and its target protein.
METHODS: Quantitative real-time PCR(qRT-PCR) was performed to detect the expression of miR-212 in PDAC tissues and pancreatic cancer cell lines. miR-212 mimic, miR-212 inhibitor and negative control were transfected into pancreatic cancer cells and the effect of miR-212 up-regulation and down-regulation on the proliferation, migration and invasion of cells were investigated. Furthermore, the mRNA and protein levels of Patched-1(PTCH1) were measured. Meanwhile, luciferase assays were performed to validate PTCH1 as miR-212 target in PDAC.
RESULTS: miR-212 was up-regulated in PDAC tissues and cells.Using both gain-of function and loss-of function experiments, a pro-oncogenic function of miR-212 was demonstrated in PDAC. Moreover, up-regulated of PTCH1 could attenuate the effect induced by miR-212.
CONCLUSION: These data suggest that miR-212 could facilitate PDAC progression and metastasis through targeting PTCH1, implicating a novel mechanism for the progression of PDAC.


Lică I, Jinescu G, Pavelescu C, Beuran M
Thoracoscopic left splanchnicectomy - role in pain control in unresectable pancreatic cancer. Initial experience.
Chirurgia (Bucur). 2014 May-Jun; 109(3):313-7 [PubMed] Related Publications
BACKGROUND: The management of opiate-dependent intractable abdominal pain caused by unresectable pancreatic cancer remains challenging. The aim of this study was to evaluate the safety and efficacy of thoracoscopic unilateral left splanchnicectomy for pain control in a first series of 15 patients with unresectable pancreatic cancer.
PATIENTS AND METHODS: Fifteen patients suffering from intractable pain due to unresectable pancreatic cancer (stage III and IV)underwent thoracoscopic unilateral left splanchnicectomy. To assess pain severity and the impact of this palliative procedure for pain relief, all patients completed Wong-Baker Faces Pain Rating Scale with a preoperative pain degree between 7 and 9.
RESULTS: Surgical intervention duration varied from 30 minutes to 1 hour. Pleural drainage tube was removed 24 hours postoperatively.There were no complications nor deaths.Immediate pain relief (pain degree 0-2) was achieved in all patients after thoracoscopic unilateral splanchnicectomy, same level being registered at first check-up after one month.
CONCLUSIONS: Thoracoscopic unilateral left splanchnicectomy decreases the pain substantially and significantly improves the quality of life in patients with unresectable pancreatic cancer.


Datta J, Vollmer CM
Investigational biomarkers for pancreatic adenocarcinoma: where do we stand?
South Med J. 2014; 107(4):256-63 [PubMed] Related Publications
Although the outcomes for pancreatic ductal adenocarcinoma (PDAC) remain disappointing, there has been considerable improvement in the 5-year survival rate of patients with resectable disease. As such, an R0 surgical resection (microscopic tumor clearance) offers patients with PDAC the greatest survival benefit. Carbohydrate antigen 19-9, the only US Food and Drug Administration-approved biomarker for PDAC, is a poor screening tool and is most informative after PDAC resection. Consequently, there has been a tremendous initiative to discover novel biomarkers that may aid in detecting the disease earlier, improving prognosis, and predicting response to available chemotherapy. The number of implicated biomarkers in PDAC is indeed staggering, with >2500 proposed candidates presented in the recent literature. A vast majority of these biomarkers, however, remain in the investigational phase. This review categorizes the most promising biomarkers--those closest to potential clinical application--into diagnostic and prognostic/predictive groups. The greatest challenge likely lies in the search for an effective diagnostic biomarker that can accurately discriminate between malignant and benign disease, and thereby facilitate earlier identification of those patients with PDAC who may benefit most from surgical resection.

Related: MADH4


Bronsert P, Kohler I, Timme S, et al.
Prognostic significance of Zinc finger E-box binding homeobox 1 (ZEB1) expression in cancer cells and cancer-associated fibroblasts in pancreatic head cancer.
Surgery. 2014; 156(1):97-108 [PubMed] Related Publications
BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is characterized by an aggressive biology and poor prognosis. Experimental evidence has suggested a role for the transcriptional repressor Zinc finger E-box binding homeobox 1 (ZEB1) in epithelial-mesenchymal transition, invasion, and metastasis in PDAC. ZEB1 expression has been observed in cancer cells as well as stromal fibroblasts. Our study aimed to evaluate the prognostic value of ZEB1 expression in PDAC tissue.
METHODS: Patient baseline and follow-up data were extracted from a prospectively maintained database. After clinicopathologic re-review, serial sliced tissue slides were immunostained for ZEB1, E-cadherin, vimentin, and pan-cytokeratin. ZEB1 expression in cancer cells and adjacent stromal fibroblasts was graded separately and correlated to routine histopathologic parameters and survival after resection.
RESULTS: A total of 117 cases of PDAC were included in the study. High ZEB1 expression in cancer cells and in stromal cancer-associated fibroblasts was associated with poor prognosis. There was also a trend for poor prognosis with a lymph node ratio of greater than 0.10. In line with its role as an inducer of epithelial-mesenchymal transition, ZEB1 expression in cancer cells was positively correlated with Vimentin expression and negatively with E-Cadherin expression. In multivariate analysis, stromal ZEB1 expression grade was the only independent factor of survival after resection.
CONCLUSION: Our data suggest that ZEB1 expression in cancer cells as well as in stromal fibroblasts are strong prognostic factors in PDAC. Stromal ZEB1 expression is identified for the first time as an independent predictor of survival after resection of PDAC. This observation suggests that therapies targeting ZEB1 and its downstream pathways could hit both cancer cells and supporting cancer-associated fibroblasts.


Lemke J, Schäfer D, Sander S, et al.
Survival and prognostic factors in pancreatic and ampullary cancer.
Anticancer Res. 2014; 34(6):3011-20 [PubMed] Related Publications
AIM: We analyzed survival of patients diagnosed with ampullary cancer (AC) and pancreatic ductal adenocarcinomas (PDAC).
PATIENTS AND METHODS: Between 1996 and 2009, 505 and 69 patients diagnosed with PDAC and AC, respectively, were identified. Overall survival was analyzed according to tumor entity, therapeutic approach and pathological tumor stage.
RESULTS: The 5-year overall survival rate of patients with AC (37%; 95% confidence interval 25-49%) was remarkably higher compared to PDAC patients (7%; 95% confidence interval 5-10%). In both cohorts, surgical resection improved survival. Analysis of pathological factors revealed a survival benefit for patients staged with small primary tumors (pT1/2) and exclusion of distant metastases (M0) for both PDAC and AC. Interestingly, absence of lymph node metastasis substantially improved survival in AC, but not in PDAC.
CONCLUSION: Overall survival of patients with AC is superior compared to that of patients with PDAC. Therapeutically, adequate regional lymph node dissection seems particularly important for the surgical management of AC.


Bosco G, Casarotto A, Nasole E, et al.
Preconditioning with hyperbaric oxygen in pancreaticoduodenectomy: a randomized double-blind pilot study.
Anticancer Res. 2014; 34(6):2899-906 [PubMed] Related Publications
UNLABELLED: In a prospective randomized double-blind study, we evaluated the post-operative biological and clinical effects of a single preoperative hyperbaric-treatment the day before surgery for pancreatic ductal adenocarcinoma.
PATIENTS AND METHODS: Twenty one patients were randomized and divided into two groups: group-A (10 patients, 48%) were exposed to a HyperBaric Oxygen (HBO) session the day before intervention [Pre-Intervention Day (PID)], group-B (11 patients, 52%) breathed air for 40 min in a hyperbaric chamber pressurized to 1.15 ATA (placebo group). For all patients blood samples were obtained before HBO treatment or the placebo procedure (T0); at the end of HBO session or placebo procedure (T1); on the first post-operative day (POD)(T2) and on seventh POD(T3) day, measuring interleukin (IL)-1, IL-6, IL-8, IL-10, IL-12 and TNF-α, recording postoperative pancreatic fistula (POPF), biliary-fistula, fever, intra-abdominal abscess, bleeding, pulmonary complications, delayed gastric emptying and requirement for post-operative antibiotics. The results of the present pilot study suggest that a single preoperative hyperbaric oxygen treatment on the day before surgery may reduce the complication rate in pancreatic resection.

Related: Cytokines


Infante JR, Somer BG, Park JO, et al.
A randomised, double-blind, placebo-controlled trial of trametinib, an oral MEK inhibitor, in combination with gemcitabine for patients with untreated metastatic adenocarcinoma of the pancreas.
Eur J Cancer. 2014; 50(12):2072-81 [PubMed] Related Publications
BACKGROUND: Trametinib, an oral mitogen/extracellular signal-related kinase (MEK)1/2 inhibitor, holds promise for malignancies with rat sarcoma (RAS) mutations, like pancreas cancer. This phase II study was designed to determine overall survival (OS) in patients with pancreas cancer treated with trametinib and gemcitabine. Secondary end-points included progression-free survival (PFS), overall response rate (ORR) and duration of response (DOR); safety end-points were also assessed.
METHODS: Adults with untreated metastatic adenocarcinoma of the pancreas were randomised (1:1) to receive intravenous gemcitabine 1000 mg/m(2) (weekly × 7 for 8 weeks, then days 1, 8 and 15 of 28-day cycles) plus trametinib or placebo 2mg daily. RAS mutations were determined in circulating free DNA (cfDNA) and archival tumour tissue. OS was evaluated in kirsten rat sarcoma viral oncogene homolog (KRAS) mutant and wild-type subgroups.
RESULTS: Baseline characteristics for 160 patients were similar in both treatment arms. There was no significant difference in OS (hazard ratio (HR) 0.98; 95% confidence interval (CI), 0.67-1.44; P=.453); median OS was 8.4 months with gemcitabine plus trametinib and 6.7 months with gemcitabine plus placebo. Median PFS (16 versus 15 weeks), ORR (22% versus 18%) and median DOR (23.9 versus 16.1 weeks) were also similar for trametinib and placebo arms, respectively. KRAS mutation-positive patients (n=103) showed no difference in OS between arms. Thrombocytopenia, diarrhoea, rash and stomatitis were more frequent with trametinib, as was grade 3 anaemia.
CONCLUSIONS: The addition of trametinib to gemcitabine did not improve OS, PFS, ORR or DOR in patients with previously untreated metastatic pancreas cancer. Outcomes were independent of KRAS mutations determined by cfDNA.

Related: Gemcitabine


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 Cytopathol Histpathol. 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.


OʼReilly EM, Perelshteyn A, Jarnagin WR, et al.
A single-arm, nonrandomized phase II trial of neoadjuvant gemcitabine and oxaliplatin in patients with resectable pancreas adenocarcinoma.
Ann Surg. 2014; 260(1):142-8 [PubMed] Related Publications
BACKGROUND: The role for neoadjuvant systemic therapy in resectable pancreas adenocarcinoma remains undefined.
OBJECTIVE: We evaluated the efficacy of gemcitabine and oxaliplatin administered as preoperative therapy in patients with resectable pancreas adenocarcinoma.
METHODS: Eligible patients were screened using computed tomography-pancreas angiography, laparoscopy, endoscopic ultrasonography, and fine-needle aspiration cytology to identify 38 patients who received 4 cycles of neoadjuvant gemcitabine 1000 mg/m intravenously over 100 minutes and oxaliplatin 80 mg/m intravenously over 2 hours, every 2 weeks. Patients whose tumors remained resectable at restaging proceeded to operation and subsequently received 5 cycles of adjuvant gemcitabine (1000 mg/m intravenously over 30 minutes days 1, 8, and 15 every 4 weeks). The primary endpoint was 18-month overall survival and secondary endpoints included radiological, tumor marker and pathological response to neoadjuvant therapy, time to recurrence, patterns of failure, and feasibility of obtaining preoperative core biopsies.
RESULTS: Thirty-five of 38 patients (92%) completed neoadjuvant therapy. Twenty-seven patients underwent tumor resection (resectability rate 71%), of which 26 initiated adjuvant therapy for a total of 23 patients (60.5%) who completed all planned therapy. The 18-month survival was 63% (24 patients alive). The median overall survival for all 38 patients was 27.2 months (95% confidence interval: 17-NA) and the median disease-specific survival was 30.6 months (95% confidence interval: 19-NA).
CONCLUSIONS: This study met its endpoint and provided a signal suggesting that exploration of neoadjuvant systemic therapy is worthy of further investigation in resectable pancreas adenocarcinoma. Improved patient selection and more active systemic regimens are key. Clinical trials identification: NCT00536874.

Related: Oxaliplatin Gemcitabine


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.


Swan RZ, Niemeyer DJ, Seshadri RM, et al.
The impact of regionalization of pancreaticoduodenectomy for pancreatic Cancer in North Carolina since 2004.
Am Surg. 2014; 80(6):561-6 [PubMed] Related Publications
Pancreaticoduodenectomy (PD) carries a significant risk. High-volume centers (HVCs) provide improved outcomes and regionalization is advocated. Rapid regionalization could, however, have detrimental effects. North Carolina has multiple HVCs, including an additional HVC added in late 2006. We investigated regionalization of PD and its effects before, and after, the establishment of this fourth HVC. The North Carolina Hospital Discharge Database was queried for all PDs performed during 2004 to 2006 and 2007 to 2009. Hospitals were categorized by PD volume as: low (one to nine/year), medium (10 to 19/year), and high (20/year or more). Mortality and major morbidity was assessed by comparing volume groups across time periods. Number of PDs for cancer increased 91 per cent (129 to 246 cases) at HVCs, whereas decreasing at low-volume (62 to 58 cases) and medium-volume (80 to 46 cases) centers. Percentage of PD for cancer performed at HVCs increased significantly (47.6 to 70.3%) while decreasing for low- and medium-volume centers (P < 0.001). Mortality was significantly less at HVCs (2.8%) compared with low-volume centers (10.3%) for 2007 to 2009. Odds ratio for mortality was significantly lower at HVCs during 2004 to 2006 (0.31) and 2007 to 2009 (0.34). Mortality for PD performed for cancer decreased from 6.6 to 4.6 per cent (P = 0.31). Major morbidity was not significantly different between groups within either time period; however, there was a significant increase in major morbidity at low-volume centers (P = 0.018). Regionalization of PD for cancer is occurring in North Carolina. Mortality was significantly lower at HVCs, and rapid regionalization has not detracted from the superior outcomes at HVCs.


Mathur A, Ross SB, Luberice K, et al.
Margin status impacts survival after pancreaticoduodenectomy but negative margins should not be pursued.
Am Surg. 2014; 80(4):353-60 [PubMed] Related Publications
Negative margins are the goal with pancreaticoduodenectomy for pancreatic adenocarcinoma. Thereby, margins are assessed intraoperatively with frozen section analysis and negative margins are pursued. This study was undertaken to determine the impact of margin status with pancreaticoduodenectomy for pancreatic adenocarcinoma and the value of extending resections to achieve negative margins. The intraoperative frozen section analysis and final margins for 448 patients undergoing pancreaticoduodenectomy for pancreatic adenocarcinoma were assessed and their impact on survival was determined. Median data are presented. Two hundred ninety-eight (67%) patients had negative margins (R0), an additional 110 (25%) patients had microscopically positive and macroscopically negative margins (R1), and an additional 40 (9%) patients had initially positive microscopic margins, which became negative with further resection (R1 → R0). R0 resections were more likely to have smaller tumors, earlier T grade, earlier N grade, lower American Joint Committee on Cancer stage, and less frequent extrapancreatic extension (P ≤ 0.03 for each). Survival was better with R0 resections than R1 resections (20 vs 12 months, P < 0.001); extending resections to achieve negative margins (i.e., R1 → R0) did not improve survival beyond R1 resections (14 vs 12 months, P = 0.19). Survival after pancreaticoduodenectomy is disappointing. Patients with initial negative margins do best. Positive microscopic margins reflect more aggressive tumor-specific factors and lead to abbreviated survival even with extended resections to achieve negative margins (i.e., R1 → R0). With an initial positive margin, pursuing negative margins does not improve survival and, thereby, negative margins should not be "chased."


Koh YX, Chok AY, Zheng HL, et al.
A systematic review and meta-analysis of the clinicopathologic characteristics of cystic versus solid pancreatic neuroendocrine neoplasms.
Surgery. 2014; 156(1):83-96.e2 [PubMed] Related Publications
INTRODUCTION: Cystic pancreatic neuroendocrine neoplasms (PNENs) are rare neoplasms, and presently, it is uncertain whether their behavior is similar or distinct from their solid counterparts. This study aimed to review systematically the present literature to compare the clinicopathologic characteristics of cystic PNENs versus their solid counterparts to determine whether cystic PNENs are likely to be a distinct entity from solid PNENs.
METHODS: Comparative studies of solid versus cystic PNENs studies were reviewed. Cystic and solid PNENs were compared on the basis of several clinicopathologic characteristics.
RESULTS: Seven nonrandomized case control studies compared 152 cystic versus 915 solid PNENs. Pooled analysis demonstrated that the likelihood of PNENs to be located in the head/uncinate of the pancreas was lower for cystic than solid neoplasms (27.7% vs 45.5%, odds ratio [OR] 0.452, 95% confidence interval [95% CI] 0.304-0.673, P < .001). Cystic PNENs were less likely to be functional (14% vs 24.4%, OR 0.405, 95% CI 0.221-0.742, P = .003) and were more likely to be benign/uncertain rather than malignant compared with solid PNENs (90.3% vs 65.9%, OR 3.151, 95% CI 1.297-7.652, P = .011). Cystic PNENs were more likely to have a mitotic count <2 per 10 hpf and a Ki67 index <2% (93.3% vs 72.7%, OR 4.897, 95% CI 2.139-11.209, P < .001 and 82.4% vs 54.1%, OR 4.079, 95% CI 2.177-7.641, P < .001), respectively. Cystic neoplasms were also less likely to have regional lymph node metastases than solid neoplasms (11.2% vs 28.9%, OR 0.387, 95% CI 0.219-0.685, P = .001).In this meta-analysis, there was no difference in the 5-year overall survival and 5-year disease-free survival between cystic vs solid PNENs (92.0% vs 86.8%, P .214) and (98.1% vs 83.9%, P = .185).
CONCLUSION: These findings suggest that cystic PNENs tend to be biologically less aggressive compared with their solid counterparts; more data, however, with respect to molecular analysis are required to establish whether cystic and solid PNENs were distinct pathologic entities.


Hurdle V, Ouellet JF, Dixon E, et al.
Does regional variation impact decision-making in the management and palliation of pancreatic head adenocarcinoma? Results from an international survey.
Can J Surg. 2014; 57(3):E69-74 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Management and palliation of pancreatic head adenocarcinoma is challenging. End-of-life decision-making is a variable process involving multiple factors.
METHODS: We conducted a qualitative, physician-based, 40-question international survey characterizing the impact of medical, religious, social, training and system factors on care.
RESULTS: A total of 258 international clinicians completed the survey. Respondents were typically fellowship-trained (78%), with a mean of 16 years' experience in a university-affiliated (93%) hepato-pancreato-biliary group (96%) practice. Most (91%) believed resection is potentially curative. Most patients were discussed preoperatively by multidisciplinary teams (94%) and medical assessment clinics (68%), but rarely critical care (21%). Intraoperative surgical palliation included double bypass or no intervention for locally advanced nonresectable tumours (41% and 49% v. 14% and 85%, respectively, for patients with hepatic metastases). Postoperative admission to the intensive care unit was frequent (58%). Severe postoperative complications were often treated with aggressive cardiopulmonary resuscitation, intubation and critical care (96%), with no defined time points for futility (74%). Admitting surgeons guided most end-of-life decisions (97%). Formal medical futility laws were rarely available (26%). Insurance status did not alter treatment (97%) or palliation (95%) in non-universal care regions. Clinician experience, regional culture and training background impacted treatment (all p < 0.05).
CONCLUSION: Despite remarkable overall agreement, geographic and training differences are evident in the treatment and palliation of pancreatic head adenocarcinoma.

Related: Canada USA


Hong TS, Ryan DP, Borger DR, et al.
A phase 1/2 and biomarker study of preoperative short course chemoradiation with proton beam therapy and capecitabine followed by early surgery for resectable pancreatic ductal adenocarcinoma.
Int J Radiat Oncol Biol Phys. 2014; 89(4):830-8 [PubMed] Related Publications
PURPOSE: To evaluate the safety, efficacy and biomarkers of short-course proton beam radiation and capecitabine, followed by pancreaticoduodenectomy in a phase 1/2 study in pancreatic ductal adenocarcinoma (PDAC) patients.
METHODS AND MATERIALS: Patients with radiographically resectable, biopsy-proven PDAC were treated with neoadjuvant short-course (2-week) proton-based radiation with capecitabine, followed by surgery and adjuvant gemcitabine. The primary objective was to demonstrate a rate of toxicity grade ≥ 3 of <20%. Exploratory biomarker studies were performed using surgical specimen tissues and peripheral blood.
RESULTS: The phase 2 dose was established at 5 daily doses of 5 GyE. Fifty patients were enrolled, of whom 35 patients were treated in the phase 2 portion. There were no grade 4 or 5 toxicities, and only 2 of 35 patients (4.1%) experienced a grade 3 toxicity event (chest wall pain grade 1, colitis grade 1). Of 48 patients eligible for analysis, 37 underwent pancreaticoduodenectomy. Thirty of 37 (81%) had positive nodes. Locoregional failure occurred in 6 of 37 resected patients (16.2%), and distant recurrence occurred in 35 of 48 patients (72.9%). With median follow-up of 38 months, the median progression-free survival for the entire group was 10 months, and overall survival was 17 months. Biomarker studies showed significant associations between worse survival outcomes and the KRAS point mutation change from glycine to aspartic acid at position 12, stromal CXCR7 expression, and circulating biomarkers CEA, CA19-9, and HGF (all, P<.05).
CONCLUSIONS: This study met the primary endpoint by showing a rate of 4.1% grade 3 toxicity for neoadjuvant short-course proton-based chemoradiation. Treatment was associated with favorable local control. In exploratory analyses, KRAS(G12D) status and high CXCR7 expression and circulating CEA, CA19-9, and HGF levels were associated with poor survival.

Related: Fluorouracil KRAS gene Capecitabine


Roch AM, DeWitt JM, Al-Haddad MA, et al.
Nonoperative management of main pancreatic duct-involved intraductal papillary mucinous neoplasm might be indicated in select patients.
J Am Coll Surg. 2014; 219(1):122-9 [PubMed] Related Publications
BACKGROUND: Although the natural history of intraductal papillary mucinous neoplasm (IPMN) remains unclear, large surgical series have reported malignancy in 40% to 90% of main pancreatic duct (MPD)-involved IPMN. Accordingly, the 2012 International Consensus Guidelines recommend surgical resection in patients with suspected MPD involvement. We hypothesized that nonoperative management of select patients with suspected MPD-involved IPMN might be indicated.
STUDY DESIGN: From 1992 to 2012, 362 patients underwent surgical resection for pathologically confirmed IPMN at a single academic center. A retrospective review of prospectively collected data was performed. Main pancreatic duct involvement was suspected with an MPD diameter ≥5 mm on preoperative imaging. A multivariate analysis was conducted to assess predictors of malignancy.
RESULTS: Of 362 patients, 334 had complete data for analysis. Main pancreatic duct involvement was suspected preoperatively in 171 patients. Final pathology revealed 20% high-grade dysplastic and 27% invasive IPMN (47% malignant). Preoperative cytopathology and serum carbohydrate antigen 19-9 independently predicted malignancy (p = 0.003 and p = 0.002, respectively) and invasiveness (p < 0.0001 and p = 0.001, respectively). Patients with both negative preoperative cytopathology and normal serum carbohydrate antigen 19-9 (ie, double negatives) had a lower rate of malignancy and invasiveness (28% and 8% vs 58% and 38%; p < 0.0001). The MPD diameter did not predict malignancy or invasiveness (p = 0.36 and p = 0.46, respectively).
CONCLUSIONS: Patients with suspected MPD-involved IPMN have a highly variable rate of malignancy. Despite recent International Consensus Guidelines recommendations, these data suggest that MPD diameter is not an optimal gauge of malignant risk. Nonoperative management of suspected MPD-involved IPMN in select patients, particularly double negatives, might be indicated. Depending on age and comorbidity, operative risk might outweigh the risk of malignant progression in these patients.


Bose B, Majumder S, Khan AU
Solid pseudopapillary tumour of pancreas.
Mymensingh Med J. 2014; 23(2):392-4 [PubMed] Related Publications
Solid pseudopapillary tumour of pancreas (SPT) is an extremely rare pancreatic tumour, which has a low malignant potential and occurs mainly in young women. Pathologic and imaging findings include a well defined encapsulated pancreatic mass with cystic and solid components with evidence of haemorrhage. This is a case of a 16 years old girl who presented with upper abdominal pain of long duration and epigastric mass on palpation. Computed Tomography (CT) scan demonstrated a large well defined heterogenous attenuation mass of solid enhancing and cystic non enhancing areas, arising from the head of the pancreas. Radiologically it was diagnosed as a case of pancreatic neoplasm. Fine needle aspiration cytology (FNAC) and histopathology of the biopsy material diagnosed as solid pseudopapillary tumour of pancreas.


Kuo JH, Lee JA, Chabot JA
Nonfunctional pancreatic neuroendocrine tumors.
Surg Clin North Am. 2014; 94(3):689-708 [PubMed] Related Publications
Pancreatic neuroendocrine tumors are a group of rare, heterogeneous neoplasms that have been increasing in incidence the past few decades largely because of the diagnosis of pancreatic incidentalomas on cross-sectional imaging. Although these tumors are classically associated with clinical syndromes that result from excess secretion of particular hormones, most pancreatic neuroendocrine tumors are nonfunctional tumors presenting with symptoms secondary to mass effect, metastatic disease, or as incidental findings. This article reviews the diagnostic algorithm, surgical management, and available systemic therapies for nonfunctional pancreatic neuroendocrine tumors.


Cooper AB, Holmes HM, des Bordes JK, et al.
Role of neoadjuvant therapy in the multimodality treatment of older patients with pancreatic cancer.
J Am Coll Surg. 2014; 219(1):111-20 [PubMed] Related Publications
BACKGROUND: A well-defined treatment strategy for elderly patients with resectable pancreatic cancer is lacking. Multiple reports have described highly selected older cancer patients who have successfully undergone pancreatectomy. However, multimodality therapy is essential for long-term survival, and elderly patients are at high risk for not receiving adjuvant therapy postoperatively. We sought to describe the treatment patterns and outcomes of a series of elderly patients with pancreatic cancer who were treated with a multimodality strategy that liberally used neoadjuvant therapy.
STUDY DESIGN: We retrospectively reviewed treatment plans, short-term outcomes, and overall survival of all patients 70 years old and older, presenting to our institution over a 9-year period, who were treated for potentially resectable or borderline resectable pancreatic cancer.
RESULTS: There were 179 (76%) of 236 patients treated with curative intent. Of these patients, 153 (85%) initiated neoadjuvant therapy: 74 (48%) subsequently underwent pancreatectomy and 79 did not due to disease progression (n = 46), insufficient performance status (n = 23), or other reasons (n = 10). Eleven (42%) of 26 patients who underwent surgery first received postoperative therapy. Among patients treated with curative intent, the median overall survival of all patients initiating neoadjuvant therapy (16.6 months [range 2.1 to 142.7 months]) was similar to that of patients undergoing resection primarily (15.1 months [range 5.4 to 100.8 months]), p = 0.53. After pancreatectomy, patients had a 2% in-hospital mortality rate and 91% were discharged home.
CONCLUSIONS: Eighty-five percent of all patients 70 years old and older, who underwent pancreatectomy for potentially resectable or borderline resectable pancreatic cancer, received multimodality therapy. More than 90% were discharged home. These data demonstrate a potential role for neoadjuvant therapy in selecting elderly patients for surgery, and support further studies to refine individualized treatment protocols for this high-risk population.

Related: Fluorouracil Capecitabine Gemcitabine


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