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).

Chung H, Chapman WC
Liver transplantation for metastatic neuroendocrine tumors.
Adv Surg. 2014; 48:235-52 [PubMed] Related Publications
The ideal management of NET must be addressed on a case-by-case basis, with consideration given to patient factors, disease burden, and clinical tumor activity. Outcome improvement for LT in the setting of metastatic disease requires better characterization of the biological behavior of NETs and further identification of factors to be included in the selection criteria. Box 3 summarizes the many areas that have been, and are currently, undergoing investigation. LT as an attempt for cure rather than palliation is a justified treatment option for well-selected patients with metastatic neuroendocrine tumors of the pancreas and GI system. Optimization of pretransplantation staging and patient management algorithms, patient selection, and posttransplant management options are areas that need to be better defined. Further investigations for defining reproducible prognostic factors, consistent histopathologic evaluation, and uniform preoperative staging and site-specific data are needed. With the advancement of newer treatment modalities, it is necessary to define the role of LT along with the optimal perioperative management of existing and recurrent disease.

Related: Gastrointestinal System Cancers

Poruk KE, Firpo MA, Mulvihill SJ
Screening for pancreatic cancer.
Adv Surg. 2014; 48:115-36 [PubMed] Related Publications
Even with improved cancer care generally, the incidence and death rate is increasing for pancreatic cancer. Concern exists that a further increase in deaths caused by pancreatic cancer will be seen as other causes of death, such as heart disease and other cancers, decline. Critical exploration of screening high-risk patients as a tool to reduce deaths from pancreatic cancer should be considered. Technological advances and improved understanding of pancreatic cancer biology provides an opportunity to identify and test a panel of early detection biomarkers easily, accurately, and inexpensively measured in blood, urine, stool, or saliva samples. These biomarkers may have additional usefulness in staging, stratification for treatment, establishing prognosis, and assessing response to therapy in this disease. Screening may prove to be one of several strategies to improve outcomes in a disease that has otherwise been difficult to defeat.

Marchegiani G, Fernández-del Castillo C
Is it safe to follow side branch IPMNs?
Adv Surg. 2014; 48:13-25 [PubMed] Related Publications
Management of Bd-IPMN remains challenging. Critical appraisal of the published literature reveals that the actual treatment of what is presumed to be Bd-IPMN remains unsatisfactory, with a high rate of surgically overtreated patients. Until we accrue more precise knowledge of the natural history of Bd-IPMN, management of patients with this presumed diagnosis should be individually tailored and preferably carried out in centers with a high expertise. For now, the authors strongly think that the old guidelines should be followed in most patients because these have proven to correctly identify lesions that can be safely followed. Although the new guidelines allow for follow-up of lesions greater than 3 cm, and for the most part this is safe, they should be used cautiously in younger patients because very close surveillance would be required for their long remaining lifespan.

Related: USA

Limaiem F, Arfa N, Ben Hassen E, et al.
Neuroendocrine tumours of the pancreas: a clinicopathological study of nine cases including six insulinomas.
Pathologica. 2014; 106(2):51-7 [PubMed] Related Publications
BACKGROUND: Pancreatic neuroendocrine tumours (pNET) are relatively uncommon, accounting for 1-2% of all pancreatic neoplasms. They are characterised by varying clinical presentation, tumour biology and prognosis.
AIM: To provide an updated overview on clinicopathological features, treatment and outcome of pNET.
PATIENTS AND METHODS: In our retrospective study, we reviewed 9 cases of pNET that were diagnosed at the Pathology Department of Mongi Slim Hospital over an 11-year period (2003- 2013). Relevant clinical information and microscopic slides were available in all cases and were retrospectively reviewed. The latest WHO classification (2010) was adopted.
RESULTS: Our study group included 3 men and 6 women (M/F ratio 0.5) with an age between 20 and 75 years (mean = 52 years). Pancreatic neuroendocrine tumours ranged in size from 0.5 to 10 cm (mean 4 cm). The sites of pNET were the head of the pancreas (n = 4), the body of the pancreas (n = 3) and the tail of the pancreas (n = 2). Enucleation of the tumour was performed in five cases, Three patients underwent distal pancreatectomy and splenectomy, whereas only one patient had central pancreatectomy. Histopathological examination of the surgical specimen coupled with immunohistochemical study established a diagnosis of pNET grade 1 (G1) in seven cases and grade 2 (G2) in two cases.
CONCLUSION: Pancreatic neuroendocrine tumours are a heterogeneous group of neoplasms with distinct tumour genetics, biology and clinicopathological features. Accurate clinical and pathologic diagnosis is an important first step in developing an appropriate management plan.

Gilani SM, Tashjian R, Barawi M, Al-Khafaji B
Cytologic features of solid pseudopapillary neoplasms of the pancreas: a single institutional experience based on evaluation of diagnostic utility of endoscopic ultrasound-guided fine needle aspiration (EUS-FNA).
Pathologica. 2014; 106(2):45-50 [PubMed] Related Publications
BACKGROUND: Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) is an important modality for diagnosing solid and cystic pancreatic lesions. The objectives of this retrospective study are to review the cytologic criteria used to diagnose pancreatic solid pseudopapillary neoplasms (SPNs) and to evaluate the utility of EUS-FNA by correlating cytologic and histologic samples.
CASE REVIEWS: Of the 924 pancreatic FNAs performed at our institution from January 2002 through February 2013, four histologically confirmed cases of SPN were identified; three had an initial cytologic diagnosis of SPN. All four cases lacked on-site evaluation. Cytologic smears were assessed by two reviewers for the presence of a cellular aspirate, fibrovascular stalks lined by neoplastic cells with pale to finely granular cytoplasm, and monotonous, oval nuclei containing delicate chromatin, inconspicuous nucleoli, and grooves and inclusions. Three cases were diagnosed as SPN on cytologic examination and confirmed histologically. The remaining case was deemed a pancreatic endocrine neoplasm on cytology, but SPN on final histology. The most consistent cytologic feature we encountered was the presence of a cellular aspirate containing fibrovascular stalks lined by monotonous neoplastic cells with oval nuclei and nuclear grooves.
CONCLUSION: We conclude that EUS-FNA is an effective diagnostic tool in the diagnosis of pancreatic SPNs.

Roch AM, Ceppa EP, Al-Haddad MA, et al.
The natural history of main duct-involved, mixed-type intraductal papillary mucinous neoplasm: parameters predictive of progression.
Ann Surg. 2014; 260(4):680-8; discussion 688-90 [PubMed] Related Publications
OBJECTIVE: As such, the natural history of MPD-involved IPMN is poorly understood.
BACKGROUND: The high-risk of malignancy associated with main pancreatic duct (MPD)-involved intraductal papillary mucinous neoplasm (IPMN) has been established by surgical series. The International Consensus Guidelines recommend surgical resection of MPD-involved IPMN in fit patients.
METHODS: A review of a prospectively collected database (1992-2012) of patients with IPMN undergoing primary surveillance was performed. Invasive progression was defined as invasive carcinoma on pathology and/or positive cytopathology. Analyses included univariate, logistic regression, and receiver operating characteristic curve analyses.
RESULTS: A total of 503 patients with IPMN underwent primary surveillance, 70 for MPD-involved, mixed-type IPMN. Indications for intensive surveillance of these 70 high-risk patients were comorbidities, patient choice, and early/borderline MPD dilation (42%, 51%, and 7%, respectively). Mean follow-up was 4.7 years. Nine patients (13%) progressed at a mean of 3.5 (range, 1-9) years during follow-up. Univariate analyses yielded weight loss, interval (from isolated branch-duct IPMN) to MPD involvement, diffuse MPD dilation, increase of MPD diameter, absence of extra pancreatic cysts, elevated serum CA19-9 levels, and elevated serum alkaline phosphatase levels as significant. Maximum MPD and/or branch-duct diameter were not significant. In logistic regression, diffuse MPD dilation, serum CA19-9 and serum alkaline phosphatase levels, and absence of extra pancreatic cysts were predictors of invasiveness. The receiver operating characteristic curve indicated that the combination of these 4 factors achieved an accuracy of 98% in predicting progression.
CONCLUSIONS: Primary surveillance of mixed-type IPMN may be a reasonable strategy in select patients. Diffuse MPD dilation, serum CA19-9, serum alkaline phosphatase, and absence of extrapancreatic cysts predict patients likely to progress during primary surveillance.

Croome KP, Farnell MB, Que FG, et al.
Total laparoscopic pancreaticoduodenectomy for pancreatic ductal adenocarcinoma: oncologic advantages over open approaches?
Ann Surg. 2014; 260(4):633-8; discussion 638-40 [PubMed] Related Publications
OBJECTIVE: To directly compare the oncologic outcomes of TLPD and OPD in the setting of pancreatic ductal adenocarcinoma.
BACKGROUND: Total laparoscopic pancreaticoduodenectomy (TLPD) has been demonstrated to be feasible and may have several potential advantages over open pancreaticoduodenectomy (OPD), including lower blood loss and shorter hospital stay. Whether potential advantages could allow patients to recover in a timelier manner and pursue adjuvant treatment options remains to be answered.
METHODS: We reviewed data for all patients undergoing TLPD (N = 108) or OPD (N = 214) for pancreatic ductal adenocarcinoma at our institution between January 2008 and July 2013.
RESULTS: Neoadjuvant therapy, tumor size, node positivity, and margin-positive resection were not significantly different between the 2 groups. Median length of hospital stay was significantly longer in the OPD group (9 days; range, 5-73 days) than in the TLPD group (6 days; range, 4-118 days; P < 0.001). There was a significantly higher proportion of patients in the OPD group (12%) who had a delay of greater than 90 days or who did not receive adjuvant chemotherapy at all compared with that in the TLPD group (5%; P = 0.04). There was no significant difference in overall survival between the 2 groups (P = 0.22). A significantly longer progression-free survival was seen in the TLPD group than in the OPD group (P = 0.03).
CONCLUSIONS: TLPD is not only feasible in the setting of pancreatic ductal adenocarcinoma but also has advantages such as shorter hospital stay and faster recovery, allowing patients to recover in a timelier manner and pursue adjuvant treatment options. This study also demonstrated a longer progression-free survival in patients undergoing TLPD than those undergoing OPD.

Tignanelli CJ, Herrera Loeza SG, Yeh JJ
KRAS and PIK3CA mutation frequencies in patient-derived xenograft models of pancreatic and colorectal cancer are reflective of patient tumors and stable across passages.
Am Surg. 2014; 80(9):873-7 [PubMed] Related Publications
One obstacle in the translation of advances in cancer research into the clinic is a deficiency of adequate preclinical models that recapitulate human disease. Patient-derived xenograft (PDX) models are established by engrafting patient tumor tissue into mice and are advantageous because they capture tumor heterogeneity. One concern with these models is that selective pressure could lead to mutational drift and thus be an inaccurate reflection of patient tumors. Therefore, we evaluated if mutational frequency in PDX models is reflective of patient populations and if crucial mutations are stable across passages. We examined KRAS and PIK3CA gene mutations from pancreatic ductal adenocarcinoma (PDAC) (n = 30) and colorectal cancer (CRC) (n = 37) PDXs for as many as eight passages. DNA was isolated from tumors and target sequences were amplified by polymerase chain reaction. KRAS codons 12/13 and PIK3CA codons 542/545/1047 were examined using pyrosequencing. Twenty-three of 30 (77%) PDAC PDXs had KRAS mutations and one of 30 (3%) had PIK3CA mutations. Fifteen of 37 (41%) CRC PDXs had KRAS mutations and three of 37 (8%) had PIK3CA mutations. Mutations were 100 per cent preserved across passages. We found that the frequency of KRAS (77%) and PIK3CA (3%) mutations in PDAC PDX was similar to frequencies in patient tumors (71 to 100% KRAS, 0 to 11% PIK3CA). Similarly, KRAS (41%) and PIK3CA (8%) mutations in CRC PDX closely paralleled patient tumors (35 to 51% KRAS, 12 to 21% PIK3CA). The accurate mirroring and stability of genetic changes in PDX models compared with patient tumors suggest that these models are good preclinical surrogates for patient tumors.

Related: Colorectal (Bowel) Cancer KRAS gene

Ozcan HN, Oguz B, Sen HS, et al.
Imaging features of primary malignant pancreatic tumors in children.
AJR Am J Roentgenol. 2014; 203(3):662-7 [PubMed] Related Publications
OBJECTIVE: The purpose of this article is to describe the sonographic, CT, and MRI features of primary malignant pancreatic tumors of childhood.
CONCLUSION: Most children with a pancreatic tumor present with a solid pseudopapillary tumor that is usually well marginated and has solid and cystic areas surrounded by a fibrous capsule. Pancreatoblastoma is more aggressive than solid pseudopapillary tumor. The imaging features are those of a large heterogeneous tumor. Ductal adenocarcinoma is rare in children and has a poor prognosis.

Wu C, Yi Q, Wang F, et al.
Genetic instability in patients with pancreatic cancer analyzed by SCARs and electrochemical sensors.
Clin Lab. 2014; 60(7):1169-75 [PubMed] Related Publications
BACKGROUND: Pancreatic cancer is an aggressive disease and the fourth most common cause of cancer death across the globe. It is often not diagnosed until it is advanced. It is necessary to establish a new technology to detect DNA instabilities during the progression of pancreatic cancer and to screen for new molecular markers coupled to putative unknown oncogenes.
METHODS: A total of 25 pancreatic cancer tissue specimens were analyzed by sequence-characterized amplified regions (SCARs), including two pathological types (pancreatic ductal adenocarcinoma and neuroendocrine carcinoma). There were 41 random primers and eight long fragment primers used for PCR amplification, and the difference of dNTPs consumptions were detected by nano-electrochemical sensors. Once both dATP and dGTP are significantly different in oxidation current (reduce or increase simultaneously), separate the different genes by electrophoresis, then clone and sequence the genes, and carry out homology analysis.
RESULTS: Both dGTP and dATP showed good oxidation behavior on the carbon nanotube modified glassy carbon electrode. There were 32 different fragments in malignant tissues compared with normal control, among them a SNP located in 5'UTR of the leucine zipper protein 4 gene which is significantly correlated with pancreatic cancer (OR = 9.50) and it was confirmed by direct sequencing.
CONCLUSIONS: SCARs combined with the nanoelectrochemical sensor can be used for screening genetic instabilities in pancreatic cancer, and leucine zipper protein 4 was a novel pancreatic cancer-related gene.

Frank R, Li S, Ahmad NA, et al.
Mesothelin expression in pancreatic mucinous cysts.
Am J Clin Pathol. 2014; 142(3):313-9 [PubMed] Related Publications
OBJECTIVES: Mesothelin (MSLN) is a differentiation antigen found to be overexpressed in intraductal papillary mucinous neoplasms (IPMNs) and is a potential treatment target in pancreatic ductal adenocarcinoma.
METHODS: From institutional archives, 114 cases of resected pancreatic mucinous cysts were identified, including IPMN and mucinous cystic neoplasm (MCN). Immunohistochemical analysis of MSLN was performed on representative sections.
RESULTS: MSLN was seen more frequently in neoplastic epithelial cells from IPMN (39/52; P < .0005) and MCN (9/14; P < .0001) compared with unremarkable adjacent pancreatic and bile ducts (0/57) and benign foveolar and duodenal epithelium (0/21). When present, MSLN was diffusely expressed in neoplastic epithelium and only focally expressed in adjacent ducts (8/57). No significant difference was seen (P = .26) in MLSN expression between IPMN (79%) and MCN (83%) when only presence or absence was considered.
CONCLUSION: Our findings suggest that MLSN can be used as a marker of neoplastic transformation of epithelial cells in pancreatic mucinous cysts. The findings can help identify neoplastic mucinous epithelium.

Liszka L
Ductal adenocarcinoma of the pancreas usually retained SMAD4 and p53 protein status as well as expression of epithelial-to-mesenchymal transition markers and cell cycle regulators at the stage of liver metastasis.
Pol J Pathol. 2014; 65(2):100-12 [PubMed] Related Publications
There are limited data on the biology of metastatic pancreatic ductal adenocarcinoma (PDAC). The aim of the present study was to compare the expression of immunohistochemical markers that may be involved in the development of metastatic disease in primary PDAC and in synchronous liver metastatic tissues. Thirty-two stains (corresponding to proteins encoded by 31 genes: SMAD4, TP53, ACTA2, CDH1, CDKN1A, CLDN1, CLDN4, CLDN7, CTNNB1, EGFR, ERBB2, FN1, KRT19, MAPK1/MAPK3, MAPK14, MKI67, MMP2, MMP9, MUC1 (3 antibodies), MUC5AC, MUC6, MTOR, MYC, NES, PTGS2, RPS6, RPS6KB1, TGFB1, TGFBR1, VIM) were evaluated using tissue microarray of 26 pairs of primary PDACs and their liver metastases. There were no significant differences in expression levels of examined proteins between primary and secondary lesions. In particular, metastatic PDAC retained the primary tumour's SMAD4 protein status in all and p53 protein status in all but one case. This surprising homogeneity also involved expression levels of markers of epithelial-to-mesenchymal transition as well as cell cycle regulators studied. In conclusion, the biological profiles of primary PDACs and their liver metastases seemed to be similar. Molecular alterations of PDAC related to a set of immunohistochemical markers examined in the present study were already present at the stage of localized disease.

Related: MADH4 TP53

López T, Pumarega JA, Pollack AZ, et al.
Adjusting serum concentrations of organochlorine compounds by lipids and symptoms: a causal framework for the association with K-ras mutations in pancreatic cancer.
Chemosphere. 2014; 114:219-25 [PubMed] Related Publications
In clinically aggressive diseases, patients experience pathophysiological changes that often alter concentrations of lipids and environmental lipophilic factors; such changes are related to disease signs and symptoms. The aim of the study was to compare the effects of correcting for total serum lipids (TSL) and other clinical factors on the odds of mutations in the K-ras oncogene by organochlorine compounds (OCs), in logistic models, in 103 patients with exocrine pancreatic cancer (EPC) using a causal directed acyclic graph (DAG) framework. Results and likelihood of bias were discussed in the light of possible causal scenarios. The odds of K-ras mutated EPC was associated with some TSL-corrected OCs, including p,p'-DDT (p-value: 0.008) and polychlorinated biphenyl 138 (p-trend: 0.024). When OCs were not corrected by TSL, the OR of a K-ras mutation was significant for p,p'-DDT (p-trend: 0.035). Additionally adjusting for cholestatic syndrome increased the ORs of TSL-corrected OCs. When models were adjusted by the interval from first symptom to blood extraction (ISE), the ORs increased for both TSL-corrected and uncorrected OCs. Models with TSL-corrected OCs and adjusted for cholestatic syndrome or ISE yielded the highest ORs. We show that DAGs clarify the covariates necessary to minimize bias, and demonstrate scenarios under which adjustment for TSL-corrected OCs and failure to adjust for symptoms or ISE may induce bias. Models with TSL-uncorrected OCs may be biased too, and adjusting by symptoms or ISE may not control such biases. Our findings may have implications as well for studying environmental causes of other clinically aggressive diseases.

Hsu MY, Pan KT, Chen CM, et al.
Trans-organ versus trans-mesenteric computed tomography-guided percutaneous fine-needle aspiration biopsy of pancreatic masses: feasibility and safety.
Clin Radiol. 2014; 69(10):1050-5 [PubMed] Related Publications
AIM: To evaluate the safety and efficacy of computed tomography (CT)-guided percutaneous fine-needle aspiration biopsy (FNAB) of pancreatic masses that traverses the gastrointestinal tract or solid viscera.
MATERIALS AND METHODS: From January 2002 to December 2012, 144 patients underwent 165 CT-guided biopsies of pancreatic masses. Biopsies were performed using a 21 or 22 G needle. Cytology reports, medical records, and procedure details for all patients were retrospectively reviewed to evaluate the biopsy route, complications, and diagnostic accuracy.
RESULTS: Trans-organ biopsies of pancreatic masses were safely performed via a direct pathway traversing the stomach (n = 45), colon (n = 14), jejunum (n = 4), or liver (n = 5). There were five self-limiting mesenteric haematomas along the biopsy route on immediate post-procedure CT and all patients remained asymptomatic. All haematomas occurred after a trans-mesenteric approach rather than passage through abdominal organs. Three patients had acute pancreatitis. There was no significant difference in complications and diagnostic yields between the groups. The sensitivity, specificity, positive predictive value, and negative predictive value of final FNAB cytology for malignancy were 98.3%, 100%, 100% and 71.4%, respectively. The overall accuracy was 98.4%.
CONCLUSION: Percutaneous FNAB using the trans-organ approach is a safe and effective technique to diagnose pancreatic malignancy.

Demir IE, Boldis A, Pfitzinger PL, et al.
Investigation of Schwann cells at neoplastic cell sites before the onset of cancer invasion.
J Natl Cancer Inst. 2014; 106(8) [PubMed] Related Publications
BACKGROUND: In neural invasion (NI), cancer cells are classically assumed to actively invade nerves and to cause local recurrence and pain. However, the opposite possibility, that nerves may reach cancer cells even in their preinvasive stage and thereby promote cancer spread, has not yet been genuinely considered. The present study analyzes the reaction of Schwann cells of peripheral nerves to carcinogenesis in pancreatic cancer and colon cancer.
METHODS: Two novel 3D migration and Schwann cell outgrowth assays were developed to monitor the timing and the specificity of Schwann cell migration and cancer invasion toward peripheral neurons through digital-time-lapse microscopy and after blockade of nerve growth factor (NGF) signalling via siRNA or a small-molecule inhibitor of the p75(NTR) receptor. The frequency and emergence of the Schwann cell markers Sox10, S100, ALDH1L1, and glial-fibrillary-acidic-protein (GFAP) around cancer precursor lesions were studied in human and conditional murine pancreatic and colon cancer specimens using multiple immunolabeling.
RESULTS: Schwann cells migrated toward pancreatic and colon cancer cells, but not toward benign cells, before the onset of cancer migration toward peripheral neurons. This chemoattraction was inhibited after blockade of p75(NTR)-signaling on Schwann and pancreatic cancer cells. Schwann cells were specifically detected around murine and human pancreatic intraepithelial neoplasias (PanINs) (mean percent of murine PanINs surrounded by Schwann cells = 78.9%, 95% CI = 70.9 to 86.8%, and mean percent of human PanINs surrounded by Schwann cells = 52.5%, 95% CI = 14.7 to 90.4%; human: n = 44, murine: n = 14) and intestinal adenomas (mean percent of murine adenomas surrounded by Schwann cells = 64.2%, 95% CI = 28.6 to 99.8%, and mean percent of human adenomas surrounded by Schwann cells = 17.2%, 95% CI = -126.9 to 161.4; human: n = 36, murine: n = 12). The Schwann cell presence in this premalignant stage was associated with the frequency of NI in the malignant phase.
CONCLUSIONS: Schwann cells have particular and specific affinity to cancer cells. Emergence of Schwann cells in the premalignant phase of pancreatic and colon cancer implies that, in contrast with the traditional assumption, nerves-and not cancer cells-migrate first during NI.

Zhang XF, Yin GZ, Liu QG, et al.
Does Braun enteroenterostomy reduce delayed gastric emptying after pancreaticoduodenectomy?
Medicine (Baltimore). 2014; 93(7):e48 [PubMed] Related Publications
Whether an additional Braun enteroenterostomy is necessary in reducing delayed gastric emptying (DGE) after pancreaticoduodenectomy (PD) has not yet been well investigated. Herein, in this retrospective study, 395 consecutive cases of patients undergoing classic PD from 2009 to 2013 were reviewed. Patients with and without Braun enteroenterostomy were compared in preoperative baseline characteristics, surgical procedure, postoperative diagnosis, and morbidity including DGE. The DGE was defined and classified by the International Study Group of Pancreatic Surgery recommendation. The incidence of DGE was similar in patients with or without Braun enteroenterostomy following PD (37/347, 10.7% vs 8/48, 16.7%, P = 0.220). The patients in the 2 groups were not different in patient characteristics, lesions, surgical procedure, or postoperative complications, although patients without Braun enteroenterostomy more frequently presented postoperative vomiting than those with Braun enteroenterostomy (33.3% vs 15.3%, P = 0.002). Bile leakage, pancreatic fistula, and intraperitoneal abscess were risk factors for postoperative DGE (all P < 0.05). Prokinetic agents and acupuncture were effective in symptom relief of DGE in 24 out of 45 patients and 12 out of 14 patients, respectively.The additional Braun enteroenterostomy following classic PD was not associated with a decreased rate of DGE. Postoperative abdominal complications were strongly correlated with the onset of DGE. Prokinetic agents and acupuncture could be utilized in some patients with DGE.

Van Loon K, Owzar K, Jiang C, et al.
25-Hydroxyvitamin D levels and survival in advanced pancreatic cancer: findings from CALGB 80303 (Alliance).
J Natl Cancer Inst. 2014; 106(8) [PubMed] Article available free on PMC after 01/08/2015 Related Publications
BACKGROUND: Data from animal and cell-line models suggest that vitamin D metabolism plays an important role in pancreatic tumor behavior. Although vitamin D deficiency has been implicated in numerous cancers, the vitamin D status of patients with advanced pancreatic cancer and the effect of baseline vitamin D levels on survival are unknown.
METHODS: Participants in this correlative study (CALGB 151006) were enrolled in CALGB 80303, which was a randomized trial of patients with advanced pancreatic cancer that demonstrated no difference in overall survival (OS) among patients treated with gemcitabine plus placebo vs gemcitabine plus bevacizumab. We measured baseline serum 25-hydroxyvitamin D (25[OH]D) levels and examined associations between baseline 25(OH)D levels and progression-free survival and OS using the Cox rank score test. All statistical tests were two-sided.
RESULTS: Of 256 patients with available serum, the median 25(OH)D level was 21.7ng/mL (range 4 to 77). 44.5% of patients were vitamin D deficient (25[OH]D <20ng/mL), and 32.4% were insufficient (25[OH]D ≥20 and <30ng/mL). 25(OH)D levels were lower in black patients compared with white patients, and patients of other/undisclosed race (10.7 vs 22.4 vs 20.9ng/mL, P < .001). Baseline 25(OH)D levels were not associated with PFS (HR = 1.00, 95% CI = 0.99 to 1.01, P = .60) or OS (HR = 1.00, 95% CI = 0.99 to 1.01, P = .95).
CONCLUSION: Vitamin D deficiency was highly prevalent among patients with a new diagnosis of advanced pancreatic cancer. Black patients had statistically significantly lower 25(OH)D levels than white patients. In this cohort of patients with advanced pancreatic cancer receiving gemcitabine-based chemotherapy, baseline 25(OH)D levels were not associated with PFS or OS.

Related: USA Bevacizumab (Avastin) Gemcitabine

Argon A, Nart D, Oruç N, et al.
The prognostic significance of clinicopathological features and apoptosis inhibitor proteins in pancreas ductal adenocarcinoma.
Acta Gastroenterol Belg. 2014; 77(2):229-34 [PubMed] Related Publications
INTRODUCTION: Pancreas ductal adenocarcinoma (PDAC) is among tumors with unfavorable prognosis. The aim of this study was to determine potential prognostic factors in PDAC.
MATERIALS AND METHODS: We retrospectively evaluated a total of 117 cases according to clinicopathological parameters and survivin and livin expression. We investigated the relationship between these parameters and their prognostic significance.
RESULTS: In univariate analysis, lymph node metastasis, surgical margin positivity, tumor size over 4 cm and survivin expression were associated with poorer survival but livin expression was not correlated with survival-time. In multivariate analysis, only lymph node metastasis was independent factor predicting a poorer outcome.
CONCLUSIONS: In present study, the lymph node metastasis was the strongest predictor of survival. Our finding suggest that survivin could be a target for the treatment of advanced stage resectable PDAC. Our results need to be supported by studies on larger series with advanced techniques.

Related: BIRC5

Song TY, Lim J, Kim B, et al.
The role of tumor suppressor menin in IL-6 regulation in mouse islet tumor cells.
Biochem Biophys Res Commun. 2014; 451(2):308-13 [PubMed] Related Publications
Menin is a gene product of multiple endocrine neoplasia type1 (Men1), an inherited familial cancer syndrome characterized by tumors of endocrine tissues. To gain insight about how menin performs an endocrine cell-specific tumor suppressor function, we investigated the possibility that menin was integrated in a cancer-associated inflammatory pathway in a cell type-specific manner. Here, we showed that the expression of IL-6, a proinflammatory cytokine, was specifically elevated in mouse islet tumor cells upon depletion of menin and Men(-/-) MEF cells, but not in hepatocellular carcinoma cells. Histone H3 lysine (K) 9 methylation, but not H3 K27 or K4 methylation, was involved in menin-dependent IL-6 regulation. Menin occupied the IL-6 promoter and recruited SUV39H1 to induce H3 K9 methylation. Our findings provide a molecular insight that menin-dependent induction of H3 K9 methylation in the cancer-associated interleukin gene might be linked to preventing endocrine-specific tumorigenesis.

Related: MEN1

Piovanelli B, Rovetta R, Bonadei I, et al.
Nonbacterial thrombotic endocarditis in pancreatic cancer.
Monaldi Arch Chest Dis. 2013; 80(4):189-92 [PubMed] Related Publications
Nonbacterial thrombotic endocarditis (NBTE), known as marantic endocarditis, is a phenomenon due to hypercoagulability with a complex pathogenesis. Originally described by Ziegler, the lesions of NBTE were considered to be fibrin thrombi deposited on normal or superficially degenerated cardiac valves. Numerous reports have identified the relationship between NBTE and a variety of different inflammatory states, including chronic diseases like malignancy and autoimmune disease. NBTE is a serious manifestation of prothtombotic state that is characterized by the deposition of thrombi on previously undamaged heart valves in the absence of a bloodstream bacterial infection and by the increased frequency of arterial embolic events in patients with chronic debilitating diseases. Although hypercoagulability is often seen in patients with pancreatic cancer, NBTE has rarely been reported antemortem. We report a case of marantic endocarditis in patient with pancreatic cancer, in which neurological symptoms preceded the diagnosis of pancreatic cancer.

Wang Y, Bergman S, Piedimonte S, Vanounou T
Bridging the gap between open and minimally invasive pancreaticoduodenectomy: the hybrid approach.
Can J Surg. 2014; 57(4):263-70 [PubMed] Article available free on PMC after 01/08/2015 Related Publications
BACKGROUND: Minimally invasive pancreatic surgery has evolved rapidly, but total laparoscopic pancreaticoduodenectomy has not been widely adopted owing to its technical complexity. Hybrid laparoscopy-assisted pancreaticoduodenectomy (HLAPD) combines the relative ease of open surgery with the benefits of a minimally invasive approach. This study evaluates the safety and effectiveness of the hybrid approach compared with open surgery.
METHODS: We retrospectively analyzed data of consecutive patients undergoing either hybrid or open pancreaticoduodenectomy (OPD) at our institution between September 2009 and December 2013. Demographic, operative and oncologic data were collected to compare outcomes between HLAPD and OPD.
RESULTS: Our analysis included 33 patients (HLAPD: n = 13; OPD: n = 20). There were no differences in patient demographics, comorbidities or surgical indications. The HLAPD group had significantly lower intraoperative blood loss (450 mL v. 1000 mL, p = 0.023) and shorter length of hospital stay (8 v. 12 d, p = 0.025) than the OPD group. Duration of surgery did not differ significantly between the groups. There were no differences in postoperative analgesic requirements, Clavien grade I/II or grade III/IV complications or 90-day mortality. Oncologic outcomes showed no significant differences in tumour size, R1 resection rate or number of lymph nodes harvested.
CONCLUSION: In select patients, HLAPD is a safe and effective procedure with comparable outcomes to conventional open surgery. Wider adoption of the hybrid approach will allow a greater number of patients to benefit from a less invasive procedure while facilitating the transition toward purely minimally invasive pancreaticoduodenectomy.

Jayaraman S
Balancing surgical innovation with cost and efficiency.
Can J Surg. 2014; 57(4):228-9 [PubMed] Article available free on PMC after 01/08/2015 Related Publications
The standard approach to neoplasia of the pancreatic head is pancreaticoduodenectomy, otherwise known as the Whipple procedure. Traditionally, this operation is performed through an open laparotomy incision. In high-volume centres, and when performed by appropriately qualified surgeons, the Whipple procedure is safe and effective management for diseases of the pancreatic head. Still, this operation remains one of the most complex abdominal procedures. With the proliferation of minimally invasive surgery, more complex operations are being performed using laparoscopy and other minimal access techniques. A group from McGill University and the Montreal Jewish General Hospital have prospectively evaluated their experience with minimally invasive pancreaticoduodenectomy and have compared this experience to the open approach. This is the first comparative series of its kind from Canada.

Timofte D, Livadariu R, Bintintan V, et al.
Metabolic disorders in patients operated for pancreatic cancer.
Rev Med Chir Soc Med Nat Iasi. 2014 Apr-Jun; 118(2):392-8 [PubMed] Related Publications
Adenocarcinoma of the pancreas presents a major threat with a 5-years survival rate of 5%. Whipple pancreaticoduodenectomy (PD) is the standard procedure for cephalo-pancreatic neoplasm. After an extended resection and reconstruction of superior gastrointestinal tract the digestive physiology might be heavily disrupted. A literature review of metabolic alterations of patients who suffered a major pancreatic resection is performed, regarding micronutrients, lipid absorption and pancreatogenic diabetes. Long-term survivors following PD generally have a satisfactory nutritional status although with subclinical iron, vitamin D and selenium deficiency. These patients should be followed-up also regarding these micronutrients and properly dietary supplemented when necessary, also considering the increased life expectancy. Approximately 17-25% of patients will develop insulin-dependent diabetes but pancreatogenic diabetics have elevated levels of serum insulin and minimal or absent response to food intake, as opposed to a type I diabetics, where insulin serum is normal or elevated and there is an exaggerated response to ingestion of sugar.

Estrella JS, Broaddus RR, Mathews A, et al.
Progesterone receptor and PTEN expression predict survival in patients with low- and intermediate-grade pancreatic neuroendocrine tumors.
Arch Pathol Lab Med. 2014; 138(8):1027-36 [PubMed] Related Publications
CONTEXT: The PI3K-AKT-mTOR (phosphatidylinositol 3-kinase-AKT-mammalian target of rapamycin) pathway plays a crucial role in a subset of advanced pancreatic neuroendocrine tumors (PanNETs). In breast and endometrial carcinoma, activation of this pathway inhibits progesterone receptor (PR) expression.
OBJECTIVE: To determine whether combined low expression of PR and phosphatase and tensin homologue (PTEN), a negative regulator of the PI3K-AKT-mTOR pathway, is a prognostic factor.
DESIGN: A total of 160 resected PanNETs (89 low grade and 71 intermediate grade) were analyzed for PR and PTEN immunohistochemical positivity and staining was correlated with metastasis-free survival (MFS) and overall survival (OS). Progesterone receptor staining was scored as positive by using 1% or greater as cutoff. Weak/faint staining in greater than 90% of tumor cells was considered low PTEN positivity.
RESULTS: Most PanNETs (110 cases, 69%) were both PR and PTEN positive, 45 (28%) were either PR or PTEN positive, and only 5 (3%) had a PR-negative and PTEN-low profile. Combined PR-PTEN positivity was significantly associated with MFS in patients with stage I and II disease (P <.001) and OS in all patients (P < .001) and remained a significant predictor of survival after adjusting for other factors. Patients with PR-negative-PTEN-low PanNETs had the shortest median MFS and OS, compared to those with tumors that were either PR or PTEN positive and with tumors positive for both PR and PTEN (P ≤ .001).
CONCLUSION: Combined immunohistochemical assessment of PR and PTEN may help identify a small subset of PanNETs with more aggressive behavior and may aid in risk stratification.

Related: PTEN

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.

Golan T, Kanji ZS, Epelbaum R, et al.
Overall survival and clinical characteristics of pancreatic cancer in BRCA mutation carriers.
Br J Cancer. 2014; 111(6):1132-8 [PubMed] Related Publications
BACKGROUND: The BRCA1/2 proteins are involved in regulation of cellular proliferation by DNA damage repair via homologous recombination. Therefore, BRCA1/2 mutation carriers with pancreatic cancer may have distinct biologic outcomes.
METHODS: Patients with BRCA1/2-associated pancreatic ductal adenocarcinoma (PDAC) diagnosed between January 1994 and December 2012 were identified from databases at three participating institutions. Clinical data were collected. Disease-free survival and overall survival (OS) were analysed.
RESULTS: Overall, 71 patients with PDAC and BRCA1 (n=21), BRCA2 (n=49) or both (n=1) mutations were identified. Mean age at diagnosis was 60.3 years (range 33-83), 81.7% (n=58) had any family history of malignancy; 30% (n=21) underwent primary resection. Out of 71 participants, 12 received experimental therapy; one patient had missing data, these 13 cases were excluded from OS analysis. Median OS for 58 patients was 14 months (95% CI 10-23 months). Median OS for patients with stage 1/2 disease has not been reached with 52% still alive at 60 months. Median OS for stage 3/4 was 12 months (95% CI 6-15). Superior OS was observed for patients with stage 3/4 treated with platinum vs those treated with non-platinum chemotherapies (22 vs 9 months; P=0.039).
CONCLUSION: Superior OS was observed for advanced-disease BRCA-associated PDAC with platinum exposure.

Related: Cisplatin Oxaliplatin

Hart PA, Law RJ, Frank RD, et al.
Impact of diabetes mellitus on clinical outcomes in patients undergoing surgical resection for pancreatic cancer: a retrospective, cohort study.
Am J Gastroenterol. 2014; 109(9):1484-92 [PubMed] Related Publications
OBJECTIVES: Diabetes mellitus (DM) has a bidirectional association with pancreatic cancer (PaC); however, its effect on clinical outcomes has not been thoroughly evaluated. We analyzed these data in a large sample of PaC subjects who had undergone surgical resection.
METHODS: Subjects enrolled in the Mayo Clinic Pancreatic Cancer SPORE registry from 2000 to 2010 who had resection with curative intent were identified (n=488). Tumor size, cancer stage, and postoperative median survival were evaluated. Median survivals were compared with Kaplan-Meier curves and Cox proportional hazards regression modeling.
RESULTS: A total of 275 (56%) subjects had DM before surgery. DM subjects had larger tumors compared with those without DM (3.6 cm vs. 3.3, P=0.002), even after controlling for covariates including age, body mass index, and tumor grade. Cancer stage at the time of surgery was not affected by DM status (P=0.575). Preoperative DM was not associated with an increased risk of death using a multivariable survival analysis (hazard ratio 1.06, 95% confidence interval 0.81-1.38, P=0.676). The median survival following cancer resection was similar between subjects with and without DM (24 vs. 26 months, P=0.610). In addition, postoperative survival was similar on the basis of the duration of DM (new-onset vs. long-standing) and prior use of antidiabetic treatments in diabetic subjects.
CONCLUSIONS: PaC subjects with DM have larger tumors than nondiabetic subjects. Despite this observation, preoperative DM does not negatively impact the cancer stage at the time of surgery or postoperative survival. Thus, the effect of DM on tumor size is either overshadowed by early metastatic spread of the cancer or is mitigated by the tumor resection.

Freeny PC, Saunders MD
Moving beyond morphology: new insights into the characterization and management of cystic pancreatic lesions.
Radiology. 2014; 272(2):345-63 [PubMed] Related Publications
The frequency of detection of cystic pancreatic lesions with cross-sectional imaging, particularly with multidetector computed tomography, magnetic resonance (MR) imaging, and MR cholangiopancreatography, is increasing, and many of these cystic pancreatic lesions are being detected incidentally in asymptomatic patients. Because there is considerable overlap in the cross-sectional imaging findings of cystic pancreatic lesions, and because many of these lesions being detected are smaller than 3 cm in diameter and lack any specific cross-sectional imaging features, it has become difficult to make informed decisions about patient management when the precise diagnosis remains uncertain. This article presents the limitations of cross-sectional imaging in patients with cystic pancreatic lesions, details advances in knowledge of the genomic and epigenomic changes that lead to progression of carcinogenesis, outlines the current understanding of the natural history of mucinous cystic lesions, and includes the current use and future potential of novel tumor markers and molecular analysis to characterize cystic pancreatic lesions more precisely. The need to move beyond cross-sectional imaging morphology and toward the use of new techniques to diagnose these lesions accurately is emphasized. An algorithm that uses these techniques is proposed and will hopefully lead to improved patient management.

Kim MJ, Choi DW, Choi SH, et al.
Surgical treatment of solid pseudopapillary neoplasms of the pancreas and risk factors for malignancy.
Br J Surg. 2014; 101(10):1266-71 [PubMed] Related Publications
BACKGROUND: The aim of this study was to identify clinical predictors of malignancy and surgical strategies for pancreatic solid pseudopapillary neoplasm (SPN) by analysis of surgical outcomes at a single institution.
METHODS: All patients who underwent surgery for SPN between 1995 and 2010 were identified. Histopathology slides of all patients were reviewed by a specialized pathologist and the neoplasms were classified according to the criteria of the World Health Organization 2010.
RESULTS: Of the 106 patients identified, 85 (80·2 per cent) were female, and the median age was 36 (range 10-65) years. Median tumour size was 4·5 (range 1·0-15·0) cm. Some 17 patients (16·0 per cent) were classified as having a high-grade malignant SPN. Tumour size of at least 5 cm was associated with high-grade malignant potential (P = 0·022). Although lymph nodes were removed from 40 patients (37·7 per cent), there were no nodal metastases. A total of five patients underwent en bloc resection of adjacent structures, including two with portal vein involvement. After a median follow-up of 56·9 months, two patients with high-grade malignant SPN had evidence of tumour recurrence in the lymph nodes and liver.
CONCLUSION: SPN with a diameter of 5 cm or more is associated with a high-grade malignant phenotype. Complete surgical removal is associated with low recurrence rates.

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