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).

Baghbanian M, Baghbanian A, Salmanroghani H, et al.
Efficacy of endoscopic ultrasound fine needle aspiration in diagnosing the rare (non-adenocarcinoma) tumors of pancreas.
Acta Gastroenterol Belg. 2014; 77(3):312-7 [PubMed] Related Publications
BACKGROUND: Five percent of pancreatic neoplasms are non- adenocarcinoma tumors. Clinical presentation and imaging characteristics of these tumors are similar to adenocarcinoma. This study aims at evaluating the results and efficacy of Endoscopic ultrasound guided fine needle aspiration (EUS-FNA) in diagnosing the pancreatic non-adenocarcinoma tumor in patients with solid pancreatic mass.
METHODOLOGY: The present study which is of a descriptive, prospective and case series nature, has been studying the diagnostic value of EUS-FNA in pancreatic non-adenocarcinoma tumor in 60 patients with pancreatic solid neoplasm. Cytopathologic diagnosis founded on EUS-FNA accepted as final diagnosis in unresectable ones. But the reference standard for the final diagnosis in patients with resectable tumor was surgical pathology. In patients with non diagnostic EUS-FNA specimen, final diagnosis achieved by re-FNA, Computerized Tomography (CT) guided biopsy, or surgery.
RESULTS: Ten patients (17%) found to have non-adenocarcinoma tumor. Half of them were male. EUS-FNA was diagnostic in 8 cases (80%) including the 4 neuroendocrine tumors, one gastrointestinal stromal tumor, one mucinous neoplasm, one pseudopapillary tumor, and one geant cell tumor. Surgical pathology confirmed the EUS-FNA diagnosis in five patients that had resectable tumor. However EUS-FNA recognition accepted as final diagnosis in three patients that had unresectable tumor. EUS-FNA was non-diagnostic in one patient with pancreatic lymphoma and another patient with colon cancer metastasis.
CONCLUSION: EUS FNA is a safe and effective for diagnosing the solid non-adenocarcinoma tumors as well as adenocarcinomas of pancreas.

Wong KC, Summers RM, Kebebew E, Yao J
Tumor growth prediction with hyperelastic biomechanical model, physiological data fusion, and nonlinear optimization.
Med Image Comput Comput Assist Interv. 2014; 17(Pt 2):25-32 [PubMed] Related Publications
Tumor growth prediction is usually achieved by physiological modeling and model personalization from clinical measurements. Although image-based frameworks have been proposed with promising results, different issues such as infinitesimal strain assumption, complicated optimization procedures, and lack of functional information, may limit the prediction performance. Therefore, we propose a framework which comprises a hyperelastic biomechanical model for better physiological plausibility, gradient-free nonlinear optimization for more flexible choices of models and objective functions, and physiological data fusion of structural and functional images for better subject-specificity. Experiments were performed on synthetic and clinical data to verify parameter estimation capability and prediction performance of the framework. Comparisons of using different biomechanical models and objective functions were also performed. From the experimental results on eight patient data sets, the recall, precision, and relative volume difference (RVD) between predicted and measured tumor volumes are 84.85 ± 6.15%, 87.08 ± 7.83%, and 13.81 ± 6.64% respectively.

Omonisi AE, Adisa AO, Olaofe OO, et al.
Carcinoma head of the pancreas masquerading as hepatocellular carcinoma: a case report.
Niger J Med. 2014 Oct-Dec; 23(4):355-7 [PubMed] Related Publications
BACKGROUND: Cancer of the pancreas is the primary malignant tumour of the pancreas commonly seen in the elderly. Hepatitis B virus infection is not a known marker of the disease, but patient with carcinoma head of the pancreas presenting with epigastric mass with positive hepatitis B infection in the region of the world with high endemicity for hepatitis B virus infection may cause diagnostic pitfall.
OBJECTIVE: To present a case of carcinoma head of the pancreas masqueradingas hepatocellular carcinoma
METHODS: A review of the case note, autopsy findings including gross and microscopic examinations and literature was done.
RESULTS: An elderly woman with history of weight loss and cigarette smoking.There was an epigastric mass and the liver was enlarged. The serum hepatitis B antigen was positive. Autopsy revealed an ill-defined mass in the head of the pancreas with metastasis to the liver.
CONCLUSION: Things are not always what they seem.

Related: Liver Cancer

Li G, Baek NH, Yoo K, et al.
Surgical outcomes for solid pseudopapillary neoplasm of the pancreas.
Hepatogastroenterology. 2014; 61(134):1780-4 [PubMed] Related Publications
BACKGROUND/AIMS: Solid pseudopapillary neoplasm (SPN) is a rare exocrine tumor of the pancreas with low malignant potential. This study was designed to evaluate surgical outcome of solid pseudopapillary neoplasm (SPN).
METHODOLOGY: From Between January 1994 to November 2013, 41 patients were diagnosed with SPN of the pancreas at Ajou University Medical Center and underwent surgical resection.
RESULTS: Of the 41 patients, 33(80.5%) were female and 8(19.5%) were male with a mean age of 34.5 years (range, 12-63 years). The most common location of SPN was the tail (43.9%). Mean diameters of SPN was 5.5 cm (range, 1.2- 14.5 cm). Nineteen patients (46.3%) had non-specific abdominal symptoms that had been investigated. Surgical treatment included distal pancreatectomy in 21, pancreaticoduodenectomy in 11, segmental resection of pancreas in 4, enucleation in 2, excision in 2 and surgical biopsy in 1. Thirty-nine of the 41 patients were disease-free at a median follow-up of 59 months (range, 1-125 months).
CONCLUSIONS: Patients diagnosed as SPN should receive surgical resection because of the excellent prognosis. Closed follow-up is recommended after surgery, even in patients without pathological malignant potential. For metastasis or recurrence, an aggressive surgical treatment is necessary because of the good possibility of long-term survival.

Noma Y, Kawamoto H, Kato H, et al.
The efficacy and safety of single-session endoscopic ultrasound-guided fine needle aspiration and endoscopic retrograde cholangiopancreatography for evaluation of pancreatic masses.
Hepatogastroenterology. 2014; 61(134):1775-9 [PubMed] Related Publications
BACKGROUND/AIMS: There have been limited studies evaluating single-session EUS-FNA and ERCP for evaluation of pancreatic masses. The aim of this study was to determine the safety of single-session EUS-FNA and ERCP, and to compare the diagnostic accuracies of cytodiagnosis by EUS-FNA, ERCP, and their combination.
METHODOLOGY: A total of 100 patients with pancreatic masses were prospectively enrolled. All patients underwent single-session EUS-FNA and ERCP. The main outcome measurement was frequency of post-procedural complications. Another measurement was diagnostic accuracy of cytodiagnosis by EUS-FNA, ERCP, and their combination.
RESULTS: Procedure-related pancreatitis occurred in 10 patients, but all patients were conservatively managed. Cytodiagnosis by EUS-FNA was significantly superior to ERCP in accuracy. In patients with a pancreatic head mass, 3 cases of false negative EUS-FNA were positive on ERCP. The combination procedures improved accuracy compared with EUS-FNA alone. By contrast, in the subgroup of the pancreatic body or tail mass, the combination of EUS-FNA and ERCP did not improve cytodiagnosis compared to that with EUS-FNA alone.
CONCLUSIONS: Single-session EUS-FNA and ERCP appears to be as safe as performing each procedure separately. EUS-FNA should be considered the principal procedure for cytodiagnosis. ERCP has only a complementary role in patients with pancreatic head mass.

Usuba T, Takeda Y, Murakami K, et al.
Clinical outcomes after pancreaticoduodenectomy in elderly patients at middle-volume center.
Hepatogastroenterology. 2014; 61(134):1762-6 [PubMed] Related Publications
BACKGROUND/AIMS: It has been reported that age and hospital volume are risk factors after pancreaticoduodenectomy (PD), however the mortality rate after PD at middle volume center is decreasing by surgical advances and recently PD in the elderly patients is safely performed. The aim of this study is to evaluate the safety and feasibility of PD in the patients over 80 years of age at middle-volume center.
METHODOLOGY: 60 patients who underwent PD between 2004 and 2012 were divided into two groups (≥80 and <80years). The clinical outcomes of the two groups were retrospectively analyzed.
RESULTS: There were no statistical differences in terms of preoperative parameters, co-morbidity, perioperative data, morbidity, mortality and postoperative hospital stay. We achieved zero mortality in patients over 80 years of age and 40% of them are alive without recurrence.
CONCLUSIONS: Clinical outcomes after PD in the elderly patients at middle-volume center are acceptable. Age and hospital volume are not necessarily risk factors after PD.

Suenaga M, Fujii T, Kanda M, et al.
Pattern of first recurrent lesions in pancreatic cancer: hepatic relapse is associated with dismal prognosis and portal vein invasion.
Hepatogastroenterology. 2014; 61(134):1756-61 [PubMed] Related Publications
BACKGROUND/AIMS: The aim of this study was to evaluate patterns of the initial recurrence after pancreatectomy for pancreatic cancer and risk factors in each pattern.
METHODOLOGY: This study included 209 pancreatic cancer patients who underwent pancreatectomy and of whom the detailed information on the first recurrent lesions detected by imaging during postoperative followup were available. Relapse patterns were classified into 4 groups: liver, peritoneal, local and extra-abdominal recurrences. We evaluated their associations with prognosis and various clinicopathological factors to identify relevant risk factors.
RESULTS: Cumulative numbers of patients with liver, peritoneal, local, and extra-abdominal recurrences were 81, 70, 98 and 22, respectively, for the first recurrences. Hepatic relapse was associated with significantly shorter overall survival than other sites (p<0.001) and was an independent prognostic factor in multivariate analysis (p<0.001). Pathological portal vein invasion was the only independent risk factor for hepatic relapse (p=0.045). There was no significant correlation between the depth of invasion and prevalence of hepatic relapse.
CONCLUSIONS: Hepatic relapse was associated with a dismal prognosis and with pathological portal vein invasion. Novel therapeutic strategies are therefore required to reduce the incidence of hepatic relapse, especially in patients with portal vein invasion.

El Nakeeb A, Roshdy S, Ask W, et al.
Comparative study between uncinate process carcinoma and pancreatic head carcinoma after pancreaticodudenectomy (clincopathological features and surgical outcomes).
Hepatogastroenterology. 2014; 61(134):1748-55 [PubMed] Related Publications
BACKGROUND/AIMS: Pancreatic head cancer is considered to have the worst prognosis of the periampullary carcinomas. The clinicopathological features of uncinate process pancreatic cancer are poorly published.
METHODOLOGY: We retrospectively studied patients who underwent pancreaticodudenectomy (PD) for pancreatic head adenocarcinoma. This study included three groups of patients. Group A patients with pure pancreatic head carcinoma (PPHC), group B patients with combined head and uncinate process carcinoma (CPHUC) and group C patients with pure uncinate process carcinoma (PUPC). Preoperative, intraoperative and postoperative variables were collected.
RESULTS: The study included 157 patients. Jaundice was the most common presenting symptoms in PPHC and CPHUC. Abdominal pain was the most common presenting symptoms in PUPC. The mean common bile duct (CBD) and pancreatic duct diameters were significantly smallest in PUPC group (P=0.0001). The venous invasion was significantly observed more in PUPC group and vascular resection was done in 50% of cases. The number of patients with microscopically residual tumor was significantly highest in PUPC group after PD than in other two groups (P=0.001). Recurrence rate occurred in 54.2% in PUPC group, 34.8% in CPHUC group and 22.7% in PPUC group after PD (P=0.007). The median survival was 19 months in PPHC groups, 16 months in CPHUC group, 14 months in PUPC group (P= 0.02).
CONCLUSIONS: PUPC presented with abdominal pain with more vascular infiltration. The recurrence rate was common after PD for uncinate process carcinoma especially locoregional recurrence and the overall survival rate was found to be lower for PUPC.

Maeda T, Konishi K, Tanouez K, et al.
Minimally invasive image analysis of biliary-pancreatic structure for preoperative simulation.
Hepatogastroenterology. 2014; 61(134):1744-7 [PubMed] Related Publications
For preoperative assessment of the pancreatic tumors, we developed minimally invasive method to extract the pancreatic duct from multidetector row computed tomography (MD-CT) images and to visualize the biliarypancreatic structures, tumor and adjacent organs simultaneously using an image workstation.

Seicean A, Tefas C, Ungureanu B, Săftoiu A
Endoscopic ultrasound guided radiofrequency ablation in pancreas.
Hepatogastroenterology. 2014; 61(134):1717-21 [PubMed] Related Publications
Radiofrequency ablation of the pancreas represents a more effective tumor-destruction method compared to other ablation techniques. The endoscopic ultrasound guided radiofrequency ablation is indicated for locally advanced, non-metastatic pancreatic adenocarcinoma, without the need of general anesthesia and fast recovery. The main limitations are the encasement of the mesenteric vessels or of the common bile duct in the head pancreatic tumours. The technique is feasible, effective and relatively safe in porcine models, with minimal evidence of fat necrosis in intra-pancreatic and/or extra-pancreatic adipose tissue. It has been successfully applied on insulinomas and pancreatic adenocarcinoma in humans, with few complications, such as duodenal bleeding or mild abdominal pain. Other side effects as biliary fistula, pancreatic fistula or acute pancreatitis seen in intraoperative settings of radiofrequency ablation, have not been reported in endoscopic ultrasound guided radiofrequency ablation.

Sato Y, Sawada N, Shimada M, et al.
Hybrid laparoscopic complete untinatectomy of pancreas by Shuriken shaped umbilicoplasty with sliding windows method.
Hepatogastroenterology. 2014; 61(134):1486-8 [PubMed] Related Publications
In this study, we demonstrated the complete resection of untinate process that was performed by the hybrid laparoscopic surgery using our original new technique of Shuriken shaped umbilicoplasty with sliding window`s method. A 70-year-old weman was hospitalized for surgery of intraductal papillary mucinous neoplasm located in the uncinate process of pancreas. Under general anesthesia, a Shuriken shaped umbilical skin incision was made by 7 cm in horizontal and 4cm longitudinal width with 3cm round skin incision. The intermediate skin between outside and inside skin incision was removed. Subcutaneous tissue around the umbilicus and the upper abdominal subcutaneous region was dissected, and the 8cm of upper abdominal minilaparotomy was performed. The complete resection of untinate process was performed by hybrid laparoscopic procedure with the hand-assisted or the laparo-assisted manner. The umbilicoplasty of only 3cm round skin wound was made by the reefing of subcutaneous suture with 5-0 absorbable suture. The patient suffered from pancreas leakage from pancreas stump, however it was recovered spontaneously. Our new procedure could be used for PD, DP, and Major hepatectomy with the hybrid laparoscopic procedure. It might be considered that our method is good for both cosmetic and safety benefits in HPB surgery.

El Nakeeb A, El Shobary M, El Dosoky M, et al.
Prognostic factors affecting survival after pancreaticoduodenectomy for pancreatic adenocarcinoma (single center experience).
Hepatogastroenterology. 2014 Jul-Aug; 61(133):1426-38 [PubMed] Related Publications
BACKGROUND: Pancreatic cancer is considered to have the worst prognosis of the periampullary carcinomas. This retrospective study was to determine prognostic factors for survival after pancreaticoduodenectomy in patients had pancreatic carcinoma.
METHODS: We retrospectively studied all patients who underwent PD for pancreatic adenocarcinoma originating from the head, neck or uncinate process from January 1996 to January 2011 in our center. Preoperative variables, intraoperative variables and postoperative variables were collected.
RESULTS: The study included 480 patients (282 males and 198 females with a median age of 53 years. At the time of analysis, 180 (37.5%) patients were still alive. The median survival was 19 months. This corresponded to a 1-, 3-, and 5-year actuarial survival of 44 %, 20%, and 15% respectively. Mass size less than 2 cm (P=0.0001), lymph node ratio (P=0.0001), safety margin (P=0.0001), perineural, perivascular infiltration, age above 60 years (P=0.03), gender, preoperative bilirubin, SGPT, liver status, pre and postoperative CEA, CA19- 9 (P=0.0001) were significant predictors of survival.
CONCLUSION: Mass size less than 2 cm, lymph node ratio, safety margin, perineural, perivascular infiltration, age above 60 years, gender, liver status, pre and postoperative CEA, CA19-9 are important predictors of survival in patients undergoing PD for pancreatic cancer.

Zheng YY, Tang CW, Xu YQ, et al.
Hepatic arterial infusion chemotherapy reduced hepatic metastases from pancreatic cancer after pancreatectomy.
Hepatogastroenterology. 2014 Jul-Aug; 61(133):1415-20 [PubMed] Related Publications
BACKGROUND/AIMS: This study aims to investigate the safety and efficacy of hepatic arterial infusion chemotherapy (HAIC) on liver metastases from pancreatic cancer after pancreatectomy.
METHODOLOGY: We randomly assigned 106 patients with pancreatic cancer after pancreatectomy between 2005 and 2010 to receive 2 cycles of HAIC plus 4 cycles of systemic chemotherapy (Combined Therapy) or 6 cycles of systemic chemotherapy alone (Monotherapy). Both the HAIC and systemic chemotherapy regimen consisted of a 5-hour infusion of 5-fluorouracil 1000 mg/m2 on day 1 followed by gemcitabine 800 mg/m2 as an over 30-min infusion on day 1 and day 8. The treatment was started on an average of 21.2 days after surgery and repeated every 4 weeks. The disease-free survival, overall survival and liver metastases-free survival were compared.
RESULTS: There was no significant difference in adverse effects between two groups. Significant differences were found in 3-year overall survival (Combined Therapy, 23.08 %; Monotherapy, 14.81%; P=0.0473) and liver metastases-free survival (Combined Therapy, 80.77%; Monotherapy, 55.56%; P=0.0014).
CONCLUSIONS: HAIC effectively and safely prevents liver metastases and improves the prognosis of patients with pancreatic cancer after pancreatectomy.

Related: Fluorouracil Gemcitabine

Meng Z, Zhang X, Zheng Q, et al.
Acute pancreatitis as an early indicator of pancreatic head carcinoma.
Hepatogastroenterology. 2014 Jul-Aug; 61(133):1201-6 [PubMed] Related Publications
BACKGROUND: The purpose of this study was to determine if AP is an indicator of pancreatic head carcinoma, and if it is associated with disease stage.
METHODS: A retrospective review of the medical records of 154 patients with pancreatic head cancer who were treated from January 2006 to December 2011 was conducted. Patients were divided into 2 groups: those with AP and those without. Data extracted and compared including age, gender, the presence of AP, and laboratory results.
RESULTS: This study included 103 males (67.8%) and 49 females (32.9%), with an age range of 38-83 years. The frequency of main pancreatic duct dilation (MPD) was higher in patients without pancreatitis than in patients with AP (P = 0.018). There were 18, 14, 4, and 2 patients in the AP group, and 34, 26, 31, and 23 patients in nonpancreatitis group with stage I, II, III, and IV disease, respectively, (P = 0.007). The median length of tumors in AP group was 3.41 cm, and that in the non-pancreatitis group was 4.15 cm (P = 0.028).No correlation was found between disease stage and the presence of MPD dilatation (P = 0.646). The area under the receiver operating characteristic curve (AUC) of 0.66 (P = 0.003; 95% confidence interval [CI] 0.568-0.753) indicated that AP itself was insufficient for predicting disease stage.
CONCLUSIONS: AP is an early manifestation of pancreatic head carcinoma, although the presence of AP is insufficient to predict disease stage.

Related: Cancer Screening and Early Detection

Herrigel DJ, Moss RA
Diabetes mellitus as a novel risk factor for gastrointestinal malignancies.
Postgrad Med. 2014; 126(6):106-18 [PubMed] Related Publications
Evidence of an emerging etiologic link between diabetes mellitus and several gastrointestinal malignancies is presented. Although a correlation between pancreatic cancer and diabetes mellitus has long been suspected, the potential role diabetes mellitus plays in the pathogenicity of both hepatocellular carcinoma and colon cancer is becoming increasingly well defined. Further supporting the prospect of etiologic linkage, the association of diabetes mellitus with colon cancer is consistently demonstrated to be independent of obesity. An increasing incidence of diabetes and obesity in the United States has led to a recent surge in incidence of hepatocellular cancer on the background of nonalcoholic fatty liver disease, and this disease is expected to commensurately grow in incidence. Widespread recognition of this emerging risk factor may lead to a change in screening practices. Although the mechanisms underlying the correlation are still under investigation, the role of insulin, the insulin-like growth factor-I, and related binding and signaling pathways as regulators of cell growth and cell proliferation are implicated in carcinogenesis and tumor growth. The potential role of metformin and other medications for diabetes mellitus in the chemoprevention, carcinogenesis, and treatment of gastrointestinal malignancies is also presented.

Related: Colorectal (Bowel) Cancer Liver Cancer

Wei IH, Harmon CM, Arcerito M, et al.
Tumor-associated macrophages are a useful biomarker to predict recurrence after surgical resection of nonfunctional pancreatic neuroendocrine tumors.
Ann Surg. 2014; 260(6):1088-94 [PubMed] Related Publications
OBJECTIVE: Patients with nonfunctional pancreatic neuroendocrine tumors (NF-PNETs) have poorer survival than those with functional PNETs. Our objective was to identify risk factors for recurrence after resection to better define surveillance parameters to improve long-term outcomes.
METHODS: A retrospective analysis was performed for NF-PNET patients who underwent resection at the University of Michigan from 1995 to 2012. Immunohistochemical staining of tissues from patients with and without disease recurrence was performed for Ki-67 and the macrophage marker CD68, as tumor-associated macrophages are important for PNET development and progression. Clinicopathological factors and patient outcomes were measured.
RESULTS: Ninety-seven NF-PNET patients underwent surgical resection. There was a recurrence rate of 14.4% (14/97). The median time to recurrence was 0.61 years, with 10 (71%) patients recurring within the first 2 years. Six of 7 patients (86%) monitored at 6-month surveillance intervals were diagnosed with recurrence on their first computed tomographic scan or during the intervening intervals. By Cox proportional hazards analysis, the most significant independent risk factors for recurrence were higher grade, stage, and intraoperative blood loss. High CD68 score and Ki-67 index correlated with recurrence risk, and Ki-67 index inversely correlated with time to recurrence. In patients who otherwise had few risk factors, a high CD68 score was a significant prognostic factor for recurrence.
CONCLUSIONS: In patients with NF-PNETs, risk factors associated with recurrence were high EBL, grade, stage, CD68 score, and Ki-67 index. The CD68 score was an important prognostic factor in patients who otherwise had few clinicopathological risk factors; therefore, the CD68 score should be considered when planning surveillance strategies. We recommend that NF-PNET patients at high risk of recurrence undergo initial surveillance every 3 months for 2 years after surgery.

Related: USA

Diener MK, Fitzmaurice C, Schwarzer G, et al.
Pylorus-preserving pancreaticoduodenectomy (pp Whipple) versus pancreaticoduodenectomy (classic Whipple) for surgical treatment of periampullary and pancreatic carcinoma.
Cochrane Database Syst Rev. 2014; 11:CD006053 [PubMed] Related Publications
Background Pancreatic cancer is the fourth leading cause of cancer death for men and the fifth for women. The standard treatment for resectable tumours consists of a classic Whipple (CW) operation or a pylorus-preserving pancreaticoduodenectomy (PPW). It is unclear which of these procedures is more favourable in terms of survival, mortality, complications and quality of life.Objectives The objective of this systematic review is to compare the effectiveness of CW and PPW techniques for surgical treatment of cancer of the pancreatic head and the periampullary region.Search methods We conducted searches on 28 March 2006, 11 January 2011 and 9 January 2014 to identify all randomised controlled trials (RCTs),while applying no language restrictions. We searched the following electronic databases: the Cochrane Central Register of Controlled Trials (CENTRAL), the Cochrane Database of Systematic Reviews (CDSR) and the Database of Abstracts of Reviews of Effects(DARE) from The Cochrane Library (2013, Issue 4); MEDLINE (1946 to January 2014); and EMBASE (1980 to January 2014). We also searched abstracts from Digestive Disease Week and United European Gastroenterology Week (1995 to 2010). We identified no additional studies upon updating the systematic review in 2014.Selection criteria We considered RCTs comparing CW versus PPW to be eligible if they included study participants with periampullary or pancreatic carcinoma. Data collection and analysis Two review authors independently extracted data from the included studies. We used a random-effects model for pooling data. We compared binary outcomes using odds ratios (ORs), pooled continuous outcomes using mean differences (MDs) and used hazard ratios (HRs) for meta-analysis of survival. Two review authors independently evaluated the methodological quality and risk of bias of included studies according to the standards of The Cochrane Collaboration.Main results We included six RCTs with a total of 465 participants. Our critical appraisal revealed vast heterogeneity with respect to methodological quality and outcome parameters. In-hospital mortality (OR 0.49, 95% confidence interval (CI) 0.17 to 1.40; P value 0.18), overall survival (HR 0.84, 95% CI 0.61 to 1.16; P value 0.29) and morbidity showed no significant differences. However, we noted that operating time (MD -68.26 minutes, 95% CI -105.70 to -30.83; P value 0.0004) and intraoperative blood loss (MD -0.76 mL, 95%CI -0.96 to -0.56; P value < 0.00001) were significantly reduced in the PPW group. All significant results are associated with low quality of evidence as determined on the basis of GRADE (Grades of Recommendation, Assessment, Development and Evaluation) criteria.Authors' conclusions No evidence suggests relevant differences in mortality, morbidity and survival between the two operations. Given obvious clinical and methodological heterogeneity, future research must be undertaken to perform high-quality randomised controlled trials of complex surgical interventions on the basis of well-defined outcome parameters.

Huang WK, Kuo YC, Tsang NM, et al.
Concurrent chemoradiotherapy with or without induction chemotherapy versus chemotherapy alone in patients with locally advanced pancreatic cancer.
Anticancer Res. 2014; 34(11):6755-61 [PubMed] Related Publications
BACKGROUND/AIM: The role of chemoradiotherapy (CRT) in the management of locally advanced pancreatic cancer is controversial. We aimed to explore this issue by retrospectively comparing the efficacy of concurrent CRT with or without induction (CT) versus CT alone in patients with locally advanced pancreatic cancer (LAPC).
PATIENTS AND METHODS: Between January 2006 and December 2012, 55 patients with biopsy-proven LAPC were treated either with CRT (n=31) or CT alone (n=24) at the authors' Institution. CT before or after CRT were allowed. Radiation therapy was delivered with a median dose of 50.4 Gy in a single fraction of 1.8 Gy and concurrent CT was typically given with gemcitabine at a dose of 400 mg/m2 weekly. The majority of CT was gemcitabine-based (96%). Progression-free survival and overall survival were calculated from the date of diagnosis to the date of progression and to the date of death or last follow-up, respectively.
RESULTS: Patients' characteristics were not significantly different between the CRT group and CT-alone group. Nineteen (61%) patients received scheduled radiation dose of 50.4 Gy. The median cumulative dose of maintenance CT with gemcitabine after CRT was 6,500 mg/m2. The median survival was 14.6 versus 8.1 months (p=0.001) and progression-free survival was 8.7 versus 4.9 months (p<0.001) for the CRT group and CT-alone group, respectively.
CONCLUSION: Patients with LAPC treated with CRT conferred more favorable survival than those who did not receive CRT. CRT should be considered integrating into the management of LAPC.

Related: Fluorouracil Gemcitabine

Garg B, Sood N, Kaur H, Mittal D
Solid pseudopapillary tumour of pancreas: a report of 5 cases.
J Assoc Physicians India. 2014; 62(1):61-4 [PubMed] Related Publications
A solid pseudopapillary tumour of the pancreas (SPT) is a rare neoplasm accounting for less than 2% of exocrine pancreatic neoplasms. SPT occurs in adolescent young females and is mostly benign. It is a low-grade malignant tumour that may evolve years before symptoms start and has a favourable prognosis. In this report we present five cases (four females, one male, aged 16, 45, 23, 17 and 55 years, respectively) of SPT localised in the pancreas, and discuss the clinical, imaging and histologic findings with a review of the literature. We retrospectively reviewed these five patients with SPT who underwent surgical resection in our hospital with a definitive histologic diagnosis of SPT.

Rossi RE, Naik K, Navalkissoor S, et al.
Case report of multimodality treatment for metastatic parathyroid hormone-related peptide-secreting pancreatic neuroendocrine tumour.
Tumori. 2014 Jul-Aug; 100(4):153e-6e [PubMed] Related Publications
AIMS AND BACKGROUND: Hypercalcaemia due to metastatic parathyroid hormone-related peptide-secreting pancreatic neuroendocrine tumour is challenging to manage and requires a multimodality approach.
METHODS: We present a case of a woman undergoing liver transplantation for metastatic parathyroid hormone-related peptide-secreting pancreatic neuroendocrine tumour.
RESULTS: A young woman with a history of parathyroid hormone-related peptide-secreting pancreatic neuroendocrine tumour (Ki-67 5%) removed in 1998 developed bilobar liver metastases in 2004 and underwent repeated transarterial embolisations of liver tumour and therapy with somatostatin analogue. In view of symptomatic hypercalcaemia refractory to medical therapy, she underwent liver transplantation in 2006. In 2012, follow-up imaging showed a 3-cm hypervascular lesion in the posterior wall of the stomach, which was confirmed on endoscopic ultrasound and on gallium-68-octreotate positron emission tomography scan. A gastric wall resection was performed in February 2013, and biopsies showed a neuroendocrine tumour of intermediate grade (Ki-67 15%). In June 2013, a restaging imaging showed a 2.4 cm lesion in the left breast, which was reported as a primary breast cancer on biopsies, and a 14-mm tissue lesion anterior to the gastric antrum. The patient underwent surgical excision of the breast cancer followed by hormone treatment and radiotherapy. She had surgical removal of the gastric recurrence with adjuvant chemotherapy postoperatively.
CONCLUSIONS: Hypercalcaemia related to parathyroid hormone-related peptide-secreting neuroendocrine tumour can be life-threatening, and liver transplantation may be a viable option in case of liver only diffuse neuroendocrine metastases refractory to other therapies. The risk of tumour recurrence remains a significant clinical problem after liver transplantation, and only a few patients might be considered tumour-free 5 years after liver transplantation.

Related: MKI67 Liver Cancer PTHLH Breast cancer in pregnancy

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.

Munigala S, Kanwal F, Xian H, Agarwal B
New diagnosis of chronic pancreatitis: risk of missing an underlying pancreatic cancer.
Am J Gastroenterol. 2014; 109(11):1824-30 [PubMed] Related Publications
OBJECTIVES: Patients with pancreatic cancer (PaCa) sometimes present with symptoms suggestive of chronic pancreatitis (CP). We evaluated the prevalence of undiagnosed PaCa in patients with new CP diagnosis.
METHODS: This is a retrospective study with data from Veterans Health Administration national medical care data sets from fiscal year 1998-2007. A 3-year washout period was used to identify patients with preexisting PaCa and preexisting CP diagnosis.
RESULTS: Among 471,992 veterans included, 917 (0.19%) had PaCa, 2,557 (0.54%) had a preexisting CP, and 2,175 (0.46%) had a new diagnosis of CP. PaCa was diagnosed ≤2 years following CP diagnosis in 44 patients, comprising 4.80% of patients with PaCa. Following a new diagnosis of CP, the risk of PaCa diagnosis was most marked in the first year (incidence 18.04 per 1,000 person-years (py), relative risk (RR) 63.43) and became similar to risk in patients with preexisting CP in the third year. The first-year incidence of PaCa was 7.33/1,000 py in the fifth decade and reached 36.91/1,000 py after seventh decade of life. Time to PaCa diagnosis following a CP diagnosis was ≤60 days in 14 patients, 3-12 months in 25 patients, and 13-24 months in 5 patients.
CONCLUSIONS: Approximately 5% of patients with PaCa are initially misdiagnosed as CP, and in two-thirds of these patients the cancer diagnosis is delayed by >2 months. PaCa should reliably be excluded before making a new CP diagnosis in patients who are >40 years old, especially in those without heavy smoking or alcohol history.

Related: USA

Chou WC, Chen JS, Hung YS, et al.
Plasma chromogranin A levels predict survival and tumor response in patients with advanced gastroenteropancreatic neuroendocrine tumors.
Anticancer Res. 2014; 34(10):5661-9 [PubMed] Related Publications
AIM: To correlate the baseline and change of chromogranin A (CgA) levels with patient survival and tumor response in Asian patients with advanced gastro-enteropancreatic neuroendocrine tumors (GEP-NETs).
PATIENTS AND METHODS: Sixty patients with advanced GEP-NET treated in a medical center between April 2010 and April 2013 were enrolled retrospectively. Plasma CgA level was analyzed for correlation with the patient's clinical outcome and tumor response.
RESULTS: Multivariate analysis showed that independent favorable prognostic factors for overall survival were: Eastern Cooperative Oncology Groups performance score 0-1, World Health Organization tumor grade 1-2, single organ metastasis and less than twice the upper normal range of baseline CgA levels. Percentage changes in paired CgA tests (ΔCgA) of more than 17% can predict partial response or stable disease from progressive disease with 91.2% sensitivity and 82.9% specificity.
CONCLUSION: Baseline plasma CgA levels predicted overall survival and ΔCgA predicted treatment response in Asian patients with GEP-NETs.

Related: Stomach Cancer Gastric Cancer

Wall I, Schmidt-Wolf IG
Effect of Wnt inhibitors in pancreatic cancer.
Anticancer Res. 2014; 34(10):5375-80 [PubMed] Related Publications
BACKGROUND/AIM: Activated Wnt signaling in cancer cells leads to cell proliferation. It has been shown that the Wnt pathway is activated in pancreatic adenocarcinoma cells. Therefore, we tested the effect of Wnt inhibitors in human and murine pancreatic cancer cell lines.
MATERIALS AND METHODS: The Wnt inhibitors ethacrynic acid (EA), ciclopirox olamine (CIC), piroctone olamine (PO) and griseofulvin (GF) were tested in murine and human pancreatic cancer cell lines with the 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyltetrazolium bromide (MTT) assay.
RESULTS: We showed that the Wnt inhibitors significantly reduced cell viability in murine, as well as human pancreatic cancer cell lines.
CONCLUSION: These results may lead to a new therapeutic option with Wnt inhibitors for patients with pancreatic adenocarcinoma.

Ansari D, Urey C, Hilmersson KS, et al.
Apicidin sensitizes pancreatic cancer cells to gemcitabine by epigenetically regulating MUC4 expression.
Anticancer Res. 2014; 34(10):5269-76 [PubMed] Related Publications
BACKGROUND/AIM: Mucin 4 (MUC4) has been linked to resistance to gemcitabine in pancreatic cancer cells. The aim of the present study was to assess whether epigenetic control of MUC4 expression can sensitize pancreatic cancer cells to gemcitabine treatment.
MATERIALS AND METHODS: A 76-member combined epigenetics and phosphatase small-molecule inhibitor library was screened for anti-proliferative activity against the MUC4(+) gemcitabine-resistant pancreatic cancer cell line Capan-1, followed by high-content screening of protein expression.
RESULTS: Apicidin, a histone deacetylase inhibitor, showed the greatest anti-proliferative activity with a lethal dose 50 (LD50) value of 5.17 μM. Apicidin significantly reduced the expression of MUC4 and its transcription factor hepatocyte nuclear factor 4α. Combined treatment with a sub-therapeutic concentration of apicidin and gemcitabine synergistically inhibited growth of Capan-1 cells.
CONCLUSION: Apicidin appears to be a novel anti-proliferative agent against pancreatic cancer cells that may reverse chemoresistance by epigenetically regulating MUC4 expression.

Related: MUC4 Gemcitabine

Zhang CX, Qin YM, Guo LK
Correlations between polymorphisms of extracellular superoxide dismutase, aldehyde dehydrogenase-2 genes, as well as drinking behavior and pancreatic cancer.
Chin Med Sci J. 2014; 29(3):162-6 [PubMed] Related Publications
OBJECTIVE: To investigate the correlation between drinking behavior combined with polymorphisms of extracellular superoxide dismutase (EC-SOD) and aldehyde dehydrogenase-2 (ALDH2) genes and pancreatic cancer.
METHODS: The genetic polymorphisms of EC-SOD and ALDH2 were analyzed by polymerase chain reaction restriction fragment length polymorphism in the peripheral blood leukocytes obtained from 680 pancreatic cancer cases and 680 non-cancer controls. Subsequently the frequency of genotype was compared between the pancreatic cancer patients and the healthy controls.The relationship of drinking with pancreatic cancer was analyzed.
RESULTS: The frequencies of EC-SOD (C/G) and ALDH2 variant genotypes were 37.35% and 68.82% respectively in the pancreatic cancer cases, and were significantly higher than those in the healthy controls (21.03% and 44.56%, all P<0.01). People who carried EC-SOD (C/G) (OR=2.24, 95% CI= 1.81-4.03, P<0.01) or ALDH2 variant genotypes (OR=2.75, 95% CI=1.92-4.47, P<0.01) had a high risk to develop pancreatic cancer. Those who carried EC-SOD (C/G) genotype combined with ALDH2 variant genotype had a high risk for pancreatic cancer (29.56% vs. 6.76%, OR=7.69, 95% CI=3.58-10.51, P<0.01). The drinking rate of the pancreatic cancer group (64.12%) was significantly higher than that of the control group (40.15%; OR=2.66, 95% CI=1.30-4.42, P<0.01). An interaction between drinking and EC-SOD (C/G)/ALDH2 variant genotypes increased the risk of occurrence of pancreatic cancer (OR=25.00, 95% CI= 11.87-35.64, P<0.01).
CONCLUSION: EC-SOD (C/G), ALDH2 variant genotypes and drinking might be the risk factors of pancreatic cancer.

Related: Polymorphisms

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