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).

Aoyama T, Katayama Y, Murakawa M, et al.
Clinical implication of peritoneal cytology in the pancreatic cancer patients who underwent curative resection followed by adjuvant gemcitabine or S-1 chemotherapy.
Hepatogastroenterology. 2015 Jan-Feb; 62(137):200-6 [PubMed] Related Publications
BACKGROUND/AIMS: The clinical implications of peritoneal lavage cytology (CY) status in the patients who received curative resection and adjuvant chemotherapy have not been established.
METHODOLOGY: We retrospectively analyzed clinical data from 143 consecutive patients who underwent macroscopically curative resection and received adjuvant gemcitabine or S-1 chemotherapy for pancreatic cancer from 2005 to 2014 in our institution. Correlations between CY status and survival and clinicopathological features were investigated.
RESULTS: Of the 143 patients, 21 patients were peritoneal washing cytology positive (CY+) (14.7%). Although significant difference was observed in the tumor size, no other correlation between cytology status and clinicopathological parameter existed. The recurrence free survival (RFS) rates at 3 and 5 years after surgery were 5.1% and 0% in CY+ patients, respectively, and were 21.5% and 16.1% in peritoneal washing cytology negative (CY-) patients, respectively, which were significantly different (p=0.001). The OS rates at 3 and 5 years after surgery were 17.1% and 8.6% in CY+ patients, respectively, and were 26.1% and 16.1% in CY- patients, respectively, which were trend to worse in the CY+ patients (p=0.254).
CONCLUSION: The patients with CY+ are likely to experience recurrence, even after they received curative resection and adjuvant Gemcitabine or S-1 adjuvant chemotherapy.

Related: Tegafur-uracil Gemcitabine

Ishii M, Kimura Y, Imamura M, et al.
Remnant pancreas reconstruction with duct-to-duct anastomosis after middle pancreatectomy: a report of two cases.
Hepatogastroenterology. 2015 Jan-Feb; 62(137):190-4 [PubMed] Related Publications
Reconstruction of a remnant pancreas after middle pancreatectomy has generally been performed with a pancreaticoenterostomy. We report here two cases in which physiological reconstructive procedures were performed. The reconstructive procedures included pancreatic duct-to-duct anastomosis and parenchymal sutures with absorbable monofilament interrupted stitches. A pancreatic tube was inserted for decompression at the anastomotic site in both cases. The patients comprised one with pancreatic metastasis from renal cell carcinoma and another with a non-malignant insulinoma. The tumors were located in the pancreatic body. Although an International Study Group on Pancreatic Fistula classification grade B-pancreatic fistula was observed in each patient, they both resolved with conservative therapy. The pancreatic duct at the anastomosis site was patent in both cases, and no atrophic changes developed in the remnant pancreas in either patient. These outcomes confirmed that, in selected cases, this reconstructive procedure is safe and feasible for physiological reconstruction without involvement of the digestive tract.

Related: Kidney Cancer

Hu HK, Ke NW, Li A, et al.
Clinical characteristics and prognostic factors of gastroenteropancreatic neuroendocrine tumors: a single center experience in China.
Hepatogastroenterology. 2015 Jan-Feb; 62(137):178-83 [PubMed] Related Publications
BACKGROUND/AIMS: Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are a unique subgroup of tumors in the digestive system but with great clinical heterogeneity. The information on clinical characteristics and prognostic factors of Chinese patients is rather limited.
METHODOLOGY: We retrospectively analyzed the clinical features, prognostic factors of this disease in a consecutive cohort (N=294) between January 2007 and December 2012.
RESULTS: Functioning tumors accounted for 9.2%. Rectum was the most predominant GEP-NETs locations. Abdominal pain occurred in 46.5% patients which was the most common initial symptom. G1, G2 and G3 tumors accounted for 41.5%, 34.7% and 23.8%, respectively. Endoscopy provided the highest detection rate of 95.7%. Consistence between endoscopic ultrasound guided fine needle aspiration biopsy (EUS-FNAB) and surgically obtained histological Ki-67 index was 36.4%. Serum CgA test showed a 80.0% consistence with the tissue biopsy. The median follow up duration was 2.8 years (0.02-5.90 years), the median survival was 4.8 years, overall 5-year survival rate was 69.6%. We found colonic localization, tumor size larger than 20 mm, G3 tumor and metastasis were associated with worse outcome (p<0.05).
CONCLUSION: We found both consistence and differences in GEP-NETs characteristics between our study and previous reports.

Related: MKI67 Stomach Cancer Gastric Cancer

Shinkawa H, Uenishi T, Takemura S, et al.
Adjuvant S-1 chemotherapy after surgical resection for pancreatic adenocarcinoma.
Hepatogastroenterology. 2015 Jan-Feb; 62(137):169-74 [PubMed] Related Publications
BACKGROUND/AIMS: The aim of this study was determine the effectiveness of adjuvant S-1 chemotherapy for patients with resected pancreatic cancer.
METHODOLOGY: Patients with pancreatic carcinoma who underwent pancreatic resection without adjuvant S-1 chemotherapy (n = 11) or with adjuvant S-1 chemotherapy (n = 10) were included. S-1 was administered orally at a dose of 40 mg/m2 twice daily for 28 consecutive days followed by a 14-day pause. The cycle was repeated 4 times. Overall and disease-free survival curves were generated using the Kaplan-Meier method, and statistical differences between groups were analyzed using the log-rank test.
RESULTS: The disease-free survival and overall survival were longer among recipients of adjuvant S-1 chemotherapy than among those who received surgery alone (P < 0.05; 5-year disease-free survival rate, 30% versus 0%; 5-year overall survival rate, 65% vs 0%). Although dose reduction was needed in 2 patients because of grade 2 anorexia, only 1 patient with grade 2 hypoalbuminemia discontinued adjuvant chemotherapy because of long-term hospitalization.
CONCLUSIONS: S-1 administered as a single agent showed promise as an adjuvant chemotherapy for resected pancreatic cancer.

Related: Tegafur-uracil

Xu Y, Zhu F, Xu S, Liu L
Anti-tumor effect of the extract from qingyihuaji formula on pancreatic cancer by down-regulating Notch-4 and Jagged-1.
J Tradit Chin Med. 2015; 35(1):77-83 [PubMed] Related Publications
OBJECTIVE: To investigate, in terms of Notch signaling pathway, the effect on pancreatic cancer of the extract of an anti-tumor prescription--Qingyi-huaji formula (QYHJ)--from Traditional Chinese Medicine (TCM).
METHODS: Nude mice were implanted subcutaneously with human pancreatic cancer cell line SW1990 and then randomly divided into four groups: Control, QYHJ extract, Gemcitabine, and Combination of QYHJ extract and gemcitabine. Treatments were given for 21 days and tumor growth was evaluated simultaneously. Then, expression of Notch receptors (Notch-1, Notch-2, Notch-3, and Notch-4) and their Jagged ligands (Jagged-1 and Jagged-2) in dissected tumor tissue were detected by real-time quantitative reverse transcription-polymerase chain reaction and Western blot. Finally, immunohistochemistry was performed to detect CD133, a marker of pancreatic cancer stem cells (CSCs), to evaluate the impact of QYHJ extract on pancreatic CSCs.
RESULTS: QYHJ extract treatment effectively inhibited the tumor growth in nude mice. The expression of both Notch-4 and Jagged-1 were decreased significantly in QYHJ treatment groups (P < 0.05), while gemcitabine alone had no significant effect in down-regulating Jagged-1 (P > 0.05). No significant difference was observed in the ex- pression of Notch-1, Notch-2, Notch-3, and Jagged-2 between three treatment groups and control group (P > 0.05). Moreover, immunohistochemical analysis showed that the number of CD133 positive cells was significantly reduced by QYHJ treatment (P < 0.05), and the combined treatment was more effective than gemcitabine alone (P < 0.05).
CONCLUSION: The role of the extract in pancreatic cancer treatment was associated with down-regulation of Notch-4 and Jagged-1 in Notch signaling pathway. The extract could enhance the antitumor activity of gemcitabine and was more effective than gemcitabine in regulating Notch signaling pathway to some extent.

Related: Signal Transduction

Schlarb HC, Schlarb AC, Ubert HA, Schlarb CA
Solid pseudopapillary tumor of the pancreas.
W V Med J. 2015 Mar-Apr; 111(2):22-4 [PubMed] Related Publications
Solid pseudopapillary tumor is a rare tumor accounting for 1-2% of exocrine neoplasms involving the pancreas. This typically benign tumor is predominately found in young females of non-Caucasian descent between the second and fourth decades of life. Despite the reported increasing incidence of this neoplasm, many physicians are unfamiliar with this tumor, which may lead to uncertainty of diagnosis and treatment. While further delineating the clinical and imaging features of this tumor, we present two cases with review of the literature.

Karunasiri D, Lowder F, Ostrzega N, Goldfinger D
Anti-Ge2: further evidence for lack of clinical significance.
Immunohematology. 2014; 30(4):156-7 [PubMed] Related Publications
Anti-Ge2 may be immune or naturally occurring, and it reacts with an antigen on glycophorin D. Ge2 is encoded by a gene, GYPC, which is located on the long arm of chromosome 2. Anti-Ge2 is usually an immunoblobulin G (IgG) antibody. In the available literature, we have not been able to find any reported cases of proven acute hemolytic transfusion reactions caused by Anti-Ge2. We present the case of a 67-year-old man with metastatic pancreatic carcinoma who had symptomatic anemia and a hemoglobin concentration of 6.3 g/dL. During pretransfusion testing, Anti-Ge2 was identified in his serum. Only a single unit of compatible, Ge:-2 frozen red blood cells (RBCs) could be provided by the blood supplier. A second unit of crossmatched, least-incompatible, leukocyte-reduced RBCs, presumably Ge:-2, was also transfused. The transfusion was completed without incident, and the patient's hemoglobin concentration rose appropriately. Posttransfusion values for haptoglobin, lactate dehydrogenase, and urine hemoglobin were within normal limits. A monocyte monolayer assay performed on this anti-Ge2 supports the data that antibodies of this specificity do not cause hemolysis. The clinical and laboratory data obtained in our patient clearly indicated that no hemolysis of transformed RBCs occurred during and for 24 hours after transfusion. We believe that this report adds to a limited experience with anti-Ge2 and provides further evidence for concluding that, to all likelihood, this is not a clinically important RBC antibody. The risk of transfusing apparently "incompatible" (Ge:2) RBCs seems remote and should allow for timely administration of RBCs when treating patients with serious anemia.

Yang M, Zeng L, Zhang Y, et al.
TNM staging of pancreatic neuroendocrine tumors: an observational analysis and comparison by both AJCC and ENETS systems from 1 single institution.
Medicine (Baltimore). 2015; 94(12):e660 [PubMed] Related Publications
We aimed to analyze the clinical characteristics and compare the surgical outcome of pancreatic neuroendocrine tumors (p-NETs) using the 2 tumor-node-metastasis (TNM) systems by both the American Joint Committee on Cancer (AJCC) Staging Manual (seventh edition) and the European Neuroendocrine Tumor Society (ENETS). Moreover, we sought to validate the prognostic value of the new AJCC criterion. Data of 145 consecutive patients who were all surgically treated and histologically diagnosed as p-NETs from January 2002 to June 2013 in our single institution were retrospectively collected and analyzed. The 5-year overall survival (OS) rates for AJCC classifications of stages I, II, III, and IV were 79.5%, 63.1%, 15.0%, and NA, respectively, (P < 0.005). As for the ENETS system, the OS rates at 5 years for stages I, II, III, and IV were 75.5%, 72.7%, 29.0%, and NA, respectively, (P < 0.005). Both criteria present no statistically notable difference between stage I and stage II (P > 0.05) but between stage I and stages III and IV (P < 0.05), as well as those between stage II and stages III and IV (P < 0.05). Difference between stage III and IV by ENETS was significant (P = 0.031), whereas that by the AJCC was not (P = 0.144). What's more, the AJCC Staging Manual (seventh edition) was statistically significant in both uni- and multivariate analyses by Cox regression (P < 0.005 and P = 0.025, respectively). Our study indicated that the ENETS TNM staging system might be superior to the AJCC Staging Manual (seventh edition) for the clinical practice of p-NETs. Together with tumor grade and radical resection, the new AJCC system was also validated to be an independent predictor for p-NETs.

Wu W, Hong X, Li J, et al.
Solid serous cystadenoma of the pancreas: a case report of 2 patients revealing vimentin, β-catenin, α-1 antitrypsin, and α-1 antichymotrypsin as new immunohistochemistry staining markers.
Medicine (Baltimore). 2015; 94(12):e644 [PubMed] Related Publications
Solid serous cystadenoma (SCA) of the pancreas is a rare type of pancreatic solid tumors. Postoperative pathological evaluation is of particular importance for distinguishing solid SCA of the pancreas from other pancreatic solid tumors. Here we present 2 cases of solid SCA of the pancreas, both preoperatively diagnosed with pancreatic neuroendocrine tumors. One case had positive OctreoScan test. Surgical resections were done for both cases. Postoperative immunohistochemistry assays were conducted with marker panels for SCA and 2 types of pancreatic solid tumors, which were neuroendocrine tumor (pNET) and solid pseudopapillary tumor (SPT). Two cases showed typical staining patterns for SCA markers. Notably, both cases showed positivity for 4 SPT markers (vimentin, β-catenin, α-1 antitrypsin, and α-1 antichymotrypsin). Emphasis should be paid to those 4 new markers for future pathological diagnosis of solid SCA of the pancreas.

Related: CTNNB1 gene

He Z, Tian H, Song A, et al.
Quality appraisal of clinical practice guidelines on pancreatic cancer: a PRISMA-compliant article.
Medicine (Baltimore). 2015; 94(12):e635 [PubMed] Related Publications
Clinical practice guidelines (CPGs) play an important role in health care. The guideline development process should be precise and rigorous to ensure that the results are reproducible and not vague. To determine the quality of guidelines, the Appraisal of Guidelines and Research and Evaluation (AGREE) instrument was developed and introduced. The objective of this study is to assess the methodological quality of CPGs on pancreatic cancer. Five databases (included MEDLINE and EMBASE) and guideline websites were searched till April, 2014. The methodological quality of the guidelines was assessed by 4 authors independently using the AGREE II instrument. From 2526 citations, 21 relevant guidelines were included. The overall agreement among reviewers was moderate (intraclass correlation coefficient = 0.86, 95% confidence interval 0.64-0.96). The mean scores were moderate for the domains "scope and purpose" and "clarity of presentation"; however, they were low for the domains "stakeholder involvement" (31.22), "rigor of development", "applicability", and "editorial independence". These domain scores were lower when compared with international levels. There are 5 (23.81%) guidelines that described the systematic methods for searching. Moreover, only 5 (23.81%) guidelines reported that methodological expertise were included in the guideline developing teams. The quality and transparency of the development process and the consistency in the reporting of pancreatic cancer guidelines need to be improved. Many other methodological disadvantages were identified. In the future, pancreatic cancer CPGs should base on the best available evidence rigorously developed and reported. Greater efforts are needed to provide high-quality guidelines that serve as a useful and reliable tool for clinical decision making in this field.

Parisi A, Desiderio J, Cirocchi R, et al.
Road accident due to a pancreatic insulinoma: a case report.
Medicine (Baltimore). 2015; 94(12):e537 [PubMed] Related Publications
Insulinoma is a rare pancreatic endocrine tumor, typically sporadic and solitary. Although the Whipple triad, consisting of hypoglycemia, neuroglycopenic symptoms, and symptoms relief with glucose administration, is often present, the diagnosis may be challenging when symptoms are less typical. We report a case of road accident due to an episode of loss of consciousness in a patient with pancreatic insulinoma. In the previous months, the patient had occasionally reported nonspecific symptoms. During hospitalization, endocrine examinations were compatible with an insulin-producing tumor. Abdominal computerized tomography and magnetic resonance imaging allowed us to identify and localize the tumor. The patient underwent a robotic distal pancreatectomy with partial omentectomy and splenectomy. Insulin-producing tumors may go undetected for a long period due to nonspecific clinical symptoms, and may cause episodes of loss of consciousness with potentially lethal consequences. Robot-assisted procedures can be performed with the same techniques of the traditional surgery, reducing surgical trauma, intraoperative blood loss, and hospital stays.

Al Efishat M, Wolfgang CL, Weiss MJ
Stage III pancreatic cancer and the role of irreversible electroporation.
BMJ. 2015; 350:h521 [PubMed] Related Publications
About a third of patients with pancreatic cancer present with locally advanced disease that is not amenable to resection. Because these patients have localized disease, conventional ablative therapies (thermal ablation and cryoablation) have the potential to be beneficial, but their use is inherently limited in the pancreas. These limitations could be overcome by irreversible electroporation-a novel, non-thermal ablative method that is gaining popularity for the treatment of many soft tissue tumors, including those of the pancreas. This review summarizes the status of this technique in the treatment of locally advanced pancreatic cancer. Most of the evidence on efficacy and safety is based on non-randomized prospective series, which show that irreversible electroporation may improve overall survival and pain control in locally advanced pancreatic cancer. As experience with this procedure increases, randomized controlled trials are needed to document its efficacy in locally advanced pancreatic cancer more precisely.

Chen X, Zhou T, Chen M
Meta analysis of the association of cholesterol with pancreatic carcinoma risk.
J BUON. 2015 Jan-Feb; 20(1):109-13 [PubMed] Related Publications
PURPOSE: Pancreatic carcinoma is a malignant tumor with poor prognosis. This metaanalysis was conducted to investigate if there exists any association of cholesterol with pancreatic carcinoma risk.
METHODS: A literature search was performed in Cochrane Central Library, PubMed, MEDLINE, EMBASE, CNKI (China National Knowledge Infrastructure), China Biology Medical literature database (CBM), and WangFang database for relevant available articles. Dietary cholesterol and serum levels of total cholesterol (TC) were assessed and compared. Pooled relative risks (RRs) with 95% confidence intervals (CIs) were calculated.
RESULTS: A total 19 articles coming from Europe, Asia and north America were assessed in this study. There was a significant difference between highest and lowest dietary cholesterol intake for pancreatic carcinoma risk (RR=1.31, 95% CI:1.10 to 1.56, p=0.01). Moreover, in subgroup analysis, there was a significant difference between highest and lowest dietary cholesterol intake for pancreatic carcinoma risk for case-control studies (RR=1.52, 95% CI:1.23 to 1.90, p=0.04). However, no significant difference was noticed between highest and lowest dietary cholesterol intake for pancreatic carcinoma risk for cohort studies (RR=1.02, 95% CI:0.87 to 1.20, p=0.51). The meta analysis results showed a significant difference between highest and lowest dietary cholesterol for pancreatic carcinoma in Europeans (RR=1.15, 95% CI:0.86 to 1.53, p=0.05). Moreover, compared to the low serum level of TC, the high level serum TC was associated with pancreatic carcinoma risk (RR=1.00, 95% CI:0.86-1.17, p=0.03). There was a significant difference between high and low levels of serum TC for pancreatic carcinoma risk in Europeans (RR=1.03, 95% CI: 0.72 to 1.48, p=0.04).
CONCLUSION: Dietary or serum cholesterol may be associated with risk for increased pancreatic carcinoma.

Behrens G, Jochem C, Schmid D, et al.
Physical activity and risk of pancreatic cancer: a systematic review and meta-analysis.
Eur J Epidemiol. 2015; 30(4):279-98 [PubMed] Related Publications
Physical activity may prevent pancreatic cancer by regulating body weight and decreasing insulin resistance, DNA damage, and chronic inflammation. Previous meta-analyses found inconsistent evidence for a protective effect of physical activity on pancreatic cancer but those studies did not investigate whether the association between physical activity and pancreatic cancer varies by smoking status, body mass index (BMI), or level of consistency of physical activity over time. To address these issues, we conducted an updated meta-analysis following the PRISMA guidelines among 30 distinct studies with a total of 10,501 pancreatic cancer cases. Random effects meta-analysis of cohort studies revealed a weak, statistically significant reduction in pancreatic cancer risk for high versus low levels of physical activity (relative risk (RR) 0.93, 95 % confidence interval (CI) 0.88-0.98). By comparison, case-control studies yielded a stronger, statistically significant risk reduction (RR 0.78, 95 % CI 0.66-0.94; p-difference by study design = 0.07). When focusing on cohort studies, physical activity summary risk estimates appeared to be more pronounced for consistent physical activity over time (RR 0.86, 95 % CI 0.76-0.97) than for recent past physical activity (RR 0.95, 95 % CI 0.90-1.01) or distant past physical activity (RR 0.95, 95 % CI 0.79-1.15, p-difference by timing in life of physical activity = 0.36). Physical activity summary risk estimates did not differ by smoking status or BMI. In conclusion, physical activity is not strongly associated with pancreatic cancer risk, and the relation is not modified by smoking status or BMI level. While overall findings were weak, we did find some suggestion of potential pancreatic cancer risk reduction with consistent physical activity over time.

Tanaka K, Tomita H, Osada S, et al.
Significance of histopathological evaluation of pancreatic fibrosis to predict postoperative course after pancreatic surgery.
Anticancer Res. 2015; 35(3):1749-56 [PubMed] Related Publications
BACKGROUND/AIM: Pancreatic stellate cells (PSC) play a critical role in pancreatic fibrosis and the apparent diffusion coefficient (ADC) value based on the diffusion-weighted image (DWI) from magnetic resonance imaging (MRI) may be a predictor of tissue fibrosis. This study aimed to evaluate the pancreas texture from both histopathological and radiological viewpoints and to investigate the effect of pancreas texture on occurrence of postoperative pancreatic fistula (PF).
PATIENTS AND METHODS: We divided 40 patients into soft-pancreas group and hard-pancreas group, according to the histopathological evaluation of pancreatic fibrosis. We compared ADC values and occurrences of PF between the two groups.
RESULTS: Histopathological measurement lengths of interlobular and intralobular fibrosis increased significantly with the progression of fibrosis grade and PSC stage, while PSC stage correlated significantly with fibrosis grade (r=0.868, p<0.001). PF was detected in 14 out of 40 patients, including grade A in 7 patients and grade B/C in 7 patients, but there were no operative deaths. Pancreas texture (soft/hard), determined based on the combination of fibrosis grade and PSC stage, was 16/10 (no PF) and 14/0 (grade A/B/C PF) and the difference in the incidence was significant (p=0.022). Though ADC value was significantly lower in the hard-compared to the soft-pancreas group (1.48±0.42 vs. 1.73±0.27×10(-3) mm(2)/sec; p=0.033), there was no significant difference in ADC value between no PF versus grade A/B/C PF group.
CONCLUSION: Histopathological evaluation of pancreas texture correlated negatively with ADC values and is critical to predict the occurrence of PF.

Brasoveanu V, Anghel C, Barbu I, et al.
Pancreatoduodenectomy en bloc with portal and superior mesenteric artery resection--a case report and literature review.
Anticancer Res. 2015; 35(3):1613-8 [PubMed] Related Publications
BACKGROUND: Pancreatic cancer is one of the most lethal malignancies and is associated with a very poor overall survival. However, it seems that the only curative option remains an aggressive surgical approach capable of obtaining a radical resection. Unfortunately, this desiderate is even harder to be obtained when it comes to pancreatic tumors with vascular invasion.
CASE REPORT: We present the case of a 65-year-old patient who was diagnosed with a cephalopancreatic tumor invading both the portal vein and the superior mesenteric artery.
RESULTS: Whipple procedure was performed with portal and superior mesenteric artery resection; the continuity of the portal vein was established by an end-to-end anastomosis, while the superior mesenteric artery was re-implanted in the infra-renal aorta.
CONCLUSION: Due to improvements of surgical techniques and postoperative management, the postoperative morbidity and early mortality significantly decreased and enabled the surgeon to perform ultra-radical surgery with better outcome.

Karakhanova S, Ryschich E, Mosl B, et al.
Prognostic and predictive value of immunological parameters for chemoradioimmunotherapy in patients with pancreatic adenocarcinoma.
Br J Cancer. 2015; 112(6):1027-36 [PubMed] Article available free on PMC after 17/03/2016 Related Publications
BACKGROUND: Chemoradioimmunotherapy of patients with pancreatic adenocarcinoma from the CapRI trial did not show any benefit of interferon-α in addition to a 5-fluorouracil (5FU)-based treatment. The aim of this study was to identify immunological parameters in patients from this trial to be used for predictive and/or prognostic purposes.
METHODS: The following methods were used: tumour immunohistology, FACS analyses, cytokine measurement, as well as cytotoxicity and ELIspot. Immunological parameters were correlated with patients' survival using the Kaplan-Meier method.
RESULTS: Irrespective of therapy type, high lymphocyte accumulation in tumours and frequencies of NK cells and effector (eff) CD8(+) T cells in peripheral blood of the patients were associated with patients' survival. Amount of CD3(+) and effector-memory CD8(+) blood lymphocytes, expression of CD152 and interleukin (IL)-2 serum level showed a predictive value for chemoradioimmunotherapy. Tumoural accumulation of CD3(+) and CD8(+) cells was predictive for outcome of chemotherapy alone. Besides, we identified the frequencies of CD3(+) lymphocytes, effCD8(+) T cells and NK cells in the peripheral blood of the patients, and IL-10 amount in serum, to be predictive values for 5FU-based chemotherapy.
CONCLUSIONS: Immunological parameters, identified in this trial as possible markers, may be of interest in personalized medicine towards the improvement of the treatment and prognosis of pancreatic carcinoma patients.

Related: Fluorouracil IL10 Interleukin 2 (Aldesleukin)

Kozak G, Blanco FF, Brody JR
Novel targets in pancreatic cancer research.
Semin Oncol. 2015; 42(1):177-87 [PubMed] Related Publications
The initiation and progression of pancreatic ductal adenocarcinoma (PDA) occurs as a result of molecular alterations that typically result in fluctuations of transcription, protein expression, and ultimately dysregulated signaling pathways. For example, PDA is driven by key activating, gain-of-function mutations in proto-oncogenes (eg, K-Ras) along with loss of function of tumor suppressor genes (eg, p16, SMAD4). With the advent of whole-exome sequencing of PDA genomes, several key genetic alterations have been identified as drivers of PDA. While these findings have led to groundbreaking discoveries in the etiology of PDA, they have failed to provide feasible, targetable therapeutic approaches. Additionally, recent advances in PDA research have uncovered the role of the tumor microenvironment (the non-epithelial tumor cells) in PDA progression by promoting potent, acute changes in gene expression. Herein, this chapter is aimed at discussing the key genetic and non-genetic mechanisms responsible for PDA initiation and progression. Thus based on these mechanisms, we will put forth investigated and novel therapeutic targets in PDA.

Stark A, Hines OJ
Endoscopic and operative palliation strategies for pancreatic ductal adenocarcinoma.
Semin Oncol. 2015; 42(1):163-76 [PubMed] Related Publications
Malignant biliary obstruction, duodenal, and gastric outlet obstruction, and tumor-related pain are the complications of unresectable pancreatic adenocarcinoma that most frequently require palliative intervention. Surgery involving biliary bypass with or without gastrojejunostomy was once the mainstay of treatment in these patients. However, advances in non-operative techniques-most notably the widespread availability of endoscopic biliary and duodenal stents-have shifted the paradigm of treatment away from traditional surgical management. Questions regarding the efficacy and durability of endoscopic stents for biliary and gastric outlet obstruction are reviewed and demonstrate high rates of therapeutic success, low rates of morbidity, and decreased cost. Surgery remains an effective treatment modality, and still produces the most durable relief in appropriately selected patients.

Franke AJ, Rosati LM, Pawlik TM, et al.
The role of radiation therapy in pancreatic ductal adenocarcinoma in the neoadjuvant and adjuvant settings.
Semin Oncol. 2015; 42(1):144-62 [PubMed] Related Publications
Pancreatic adenocarcinoma (PCA) is associated with high rates of cancer-related morbidity and mortality. Yet despite modern treatment advances, the only curative therapy remains surgical resection. The adjuvant therapeutic standard of care for PCA in the United States includes both chemotherapy and chemoradiation; however, an optimal regimen has not been established. For patients with resectable and borderline resectable PCA, recent investigation has focused efforts on evaluating the feasibility and efficacy of neoadjuvant therapy. Neoadjuvant therapy allows for early initiation of systemic therapy and identification of patients who harbor micrometastatic disease, thus sparing patients the potential morbidities associated with unnecessary radiation or surgery. This article critically reviews the data supporting or refuting the role of radiation therapy in the neoadjuvant and adjuvant settings of PCA management, with a particular focus on determining which patients may be more likely to benefit from radiation therapy.

Li D, O'Reilly EM
Adjuvant and neoadjuvant systemic therapy for pancreas adenocarcinoma.
Semin Oncol. 2015; 42(1):134-43 [PubMed] Related Publications
The last two decades of research in the adjuvant setting of pancreas adenocarcinoma have established the value of adjuvant systemic therapy as being able to delay recurrence and increase overall survival. International standards of care in the adjuvant setting include either 6 months of gemcitabine or 5-fluorouracil and leucovorin. The added value of additional agents in the adjuvant setting is being evaluated in several large adjuvant studies. The role of a targeted agent in the adjuvant setting remains investigational. Other major areas of exploration include the integration of adjuvant immunotherapeutic approaches, which provide promise in a setting of micrometastatic disease volumes where such approaches may have greatest value.

Stauffer JA, Asbun HJ
Minimally invasive pancreatic surgery.
Semin Oncol. 2015; 42(1):123-33 [PubMed] Related Publications
Pancreatic resection is a complex procedure that involves exposure of the retroperitoneal gland, dissection around major vascular structures, and management of an intricate organ, all of which results in a procedure associated with a high morbidity. The application of minimally invasive techniques to pancreatic resection have been studied only relatively recently. This analysis of the current concepts in minimally invasive pancreatic surgery focuses on a select look at currently published series or reviews from centers and groups that have the most experience with this procedure. We aim to present a comprehensive review gained from the experiences of those who are on the leading edge of the learning curve, with an emphasis on describing the similarities and differences between the minimally invasive and open pancreatic procedure. Minimally invasive distal pancreatectomy appears to be on the verge of widespread acceptance and shows clear benefits over its open counterpart. Minimally invasive proximal (right-sided) pancreatectomy, on the other hand, appears to be limited to select centers that have been able to demonstrate promising results despite its challenges. Additionally, minimally invasive central pancreatectomy and enucleation appear feasible as experience is gained in laparoscopic and robotic pancreatic resection.

Parikh PY, Lillemoe KD
Surgical management of pancreatic cancer--distal pancreatectomy.
Semin Oncol. 2015; 42(1):110-22 [PubMed] Related Publications
Distal pancreatectomy is the standard procedure for tumors located in the body and tail of the pancreas. In the last three decades, significant progress has been made with regard to technical aspects as well as perioperative care so that excellent mortality and morbidity rates can be achieved. Recently, there is growing evidence that distal pancreatectomy may be performed laparoscopically in selected patients, offering the advantages of minimally invasive surgery. Unfortunately, the oncologic outcomes for pancreatic adenocarcinoma remain poor, in part due to the late stage of presentation in most patients. We review the history of distal pancreatectomy, discuss current indications for performing this procedure, compare operative techniques in performing distal pancreatectomy, and review both the early complications seen in patients who have undergone a distal pancreatectomy and the long-term metabolic and oncologic outcomes of these patients.

Donahue TR, Reber HA
Surgical management of pancreatic cancer--pancreaticoduodenectomy.
Semin Oncol. 2015; 42(1):98-109 [PubMed] Related Publications
Pancreaticoduodenectomy, the Whipple resection, is a complex operation that is commonly performed for patients with pancreatic ductal adenocarcinoma and other malignant or benign lesions in the head of the pancreas. It can be done with low morbidity and mortality rates, particularly when performed at high-volume hospitals and by high-volume surgeons. While it has been conventionally reserved for patients with early-stage malignant disease, it is being used increasingly for patients with locally extensive tumors who have undergone neoadjuvant therapy and downstaging. This article summarizes the role of pancreaticoduodenectomy for the treatment of patients with pancreatic cancer. It highlights the surgical staging of disease, the technical aspects of the operation and perioperative care, and the oncologic outcome.

Winner M, Goff SL, Chabot JA
Neoadjuvant therapy for non-metastatic pancreatic ductal adenocarcinoma.
Semin Oncol. 2015; 42(1):86-97 [PubMed] Related Publications
Treatment of pancreatic cancer is increasingly multimodal, with patients receiving chemotherapy, radiation, and surgical extirpation in hope of long-term cure. There is ongoing debate over the timing, sequence, and necessity of these treatments as they pertain to the spectrum of local-regional disease. Current guidelines support a neoadjuvant strategy in patients with locally advanced and borderline resectable disease. Although there is currently no high-level evidence to recommend neoadjuvant therapy for all patients, there are data to suggest that wider application of neoadjuvant therapy may be beneficial. Random-assignment prospective trials are ongoing. In this review we examine the literature addressing a neoadjuvant approach to potentially resectable, borderline resectable, and locally advanced pancreatic cancer and highlight the outcomes of preoperative emergence of latent metastatic disease, attempted resection rates, margin negative resection rates, and pathologic response to treatment.

Dudeja V, Allen PJ
Premalignant cystic neoplasms of the pancreas.
Semin Oncol. 2015; 42(1):70-85 [PubMed] Related Publications
Due to increasing utilization of cross-sectional imaging, asymptomatic pancreatic cysts are frequently being diagnosed. Many of these cysts have premalignant potential and offer a unique opportunity for cancer prevention. Mucinous cystic neoplasm and intraductal papillary mucinous neoplasm are the major premalignant cystic neoplasms of pancreas. The prediction of the risk of malignancy (incidental and future risk of malignant transformation) and balancing the risks of watchful waiting with that of operative management with associated mortality and morbidity is the key to the management of these lesions. We review the literature that has contributed to the development of our approach to the management of these cystic neoplasms. We provide an overview of the key features used in diagnosis and in predicting malignancy. Particular attention is given to the natural history and management decision making.

Singh H, Siddiqui AA
Endosonographic workup and preoperative biliary drainage for pancreatic cancer.
Semin Oncol. 2015; 42(1):59-69 [PubMed] Related Publications
Computed tomography (CT) is the primary imaging modality for initial evaluation of pancreatic cancer (PC). Endoscopic ultrasound (EUS) has a higher sensitivity for detection of PC and is better especially for lesions<3 cm. It should be the next step if the CT scan is indeterminate, or negative in the presence of high suspicion of PC based on clinical and laboratory data. EUS-guided fine-needle aspiration (FNA) should be performed for lesions found on EUS after negative or indeterminate CT, for borderline resectable pancreatic cancer (BRPC) and unresectable cancer, or if the patient is being considered for neoadjuvant or palliative chemotherapy. EUS elastography and contrast-enhanced harmonic EUS are new and promising EUS technologies that may detect lesions missed by other modalities and may help guide EUS-FNA to target lesions.

Raman SP, Chen Y, Fishman EK
Cross-sectional imaging and the role of positron emission tomography in pancreatic cancer evaluation.
Semin Oncol. 2015; 42(1):40-58 [PubMed] Related Publications
Pancreatic cancer is an extraordinarily morbid malignancy with a poor prognosis. As a result, it is imperative that imaging examinations correctly identify tumors when they are relatively small and potentially still resectable, as well as accurately stage tumors to determine which patients should undergo definitive surgery. Multidetector computed tomography (MDCT) has been established as the most important modality for both initial diagnosis and staging, although positron emission tomography (PET) and magnetic resonance imaging (MRI) both play important ancillary roles. This review discusses how these three modalities play complementary roles in tumor diagnosis and staging.

Rishi A, Goggins M, Wood LD, Hruban RH
Pathological and molecular evaluation of pancreatic neoplasms.
Semin Oncol. 2015; 42(1):28-39 [PubMed] Article available free on PMC after 01/02/2016 Related Publications
Pancreatic neoplasms are morphologically and genetically heterogeneous and include a wide variety of tumors ranging from benign to malignant with an extremely poor clinical outcome. Our understanding of these pancreatic neoplasms has improved significantly with recent advances in cancer sequencing. Awareness of molecular pathogenesis brings new opportunities for early detection, improved prognostication, and personalized gene-specific therapies. Here we review the pathological classification of pancreatic neoplasms from the molecular and genetic perspectives.

McIntyre CA, Winter JM
Diagnostic evaluation and staging of pancreatic ductal adenocarcinoma.
Semin Oncol. 2015; 42(1):19-27 [PubMed] Related Publications
Pancreatic ductal adenocarcinoma (PDA) frequently presents at an advanced and incurable stage of the disease. Common signs and symptoms of PDA include abdominal or back pain, jaundice, weight loss, pruritus, and nausea/vomiting. Diagnostic workup includes serum chemistries and CA19-9, primarily to monitor disease status and response to treatment. Imaging studies are performed to assess resectability and stage disease, and pancreatic protocol computed tomography (CT) scan or magnetic resonance imaging (MRI) are the preferred imaging studies for this purpose. Conventional staging is based on the American Joint Cancer Committee (AJCC) Staging System, 7th Edition and informs prognosis, while surgical staging systems focus specifically on assessing the likelihood of a complete (negative margins) resection with operative management. Herein, we review the presenting signs and symptoms, the diagnostic evaluation, and staging of PDA.

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