Skip to main content
Latest news
Browse specialties
Breast cancer Genitourinary cancers Lung & thoracic cancers
In focus
Next-generation sequencing: Emerging biomarkers in thyroid and NSCLCs ctDNA and bladder cancer: Current understanding and beyond ROS1 fusion-positive NSCLC NSCLC driver mutations: Discussing the importance of RET, ALK and ROS1 alterations in NSCLC Early-stage NSCLC management: Surgery, targeted treatment and immunotherapy ALK fusion-positive NSCLC: International approaches to management RET fusion-positive NSCLC: Informing on the use of pralsetinib for patients with RET fusion-positive, advanced NSCLC COVID-19 & cancer
Conferences
SABCS 2022 ESMO 2022 2022 ASCO Annual Meeting
About us
Medicine Matters Oncology
EXTENDED SEARCH
Top

14-02-2015 | Pancreatic cancer | Article

Pancreatic cancer: diagnosis and treatments

Journal: Tumor Biology

Authors: Hong-Yu Li, Zhong-Min Cui, Jiang Chen, Xiao-Zhong Guo, Ying-Yi Li

Publisher: Springer Netherlands

Login to get access

Abstract

Pancreatic cancer is one of the deadliest cancers, with exceptionally high mortality. Despite the relatively low incidence rate (10th), it is the fourth leading cause of cancer-related deaths in most developed countries. To improve the early diagnosis of pancreatic cancer and strengthen the standardized comprehensive treatment are still the main focus of pancreatic cancer research. Here, we summarized the rapid developments in the diagnosis and treatments of pancreatic cancer. Regarding diagnosis, we reviewed advances in medical imaging technology, tumor markers, molecular biology (e.g., gene mutation), and proteomics. Moreover, great progress has also been made in the treatments of this disease, including surgical resection, chemotherapy, targeted radiotherapy, targeted minimally invasive treatment, and molecular targeted therapy. Therefore, we also recapitulated the development, advantages, and disadvantages of each of the treatment methods in this review.
Literature
1.
German RR, Fink AK, Heron M, Stewart SL, Johnson CJ, et al. The accuracy of cancer mortality statistics based on death certificates in the United States. Cancer Epidemiol. 2011;35:126–31.CrossRefPubMed
2.
Siegel R, Naishadham D, Jemal A. Cancer statistics, 2013. CA Cancer J Clin. 2013;63:11–30.CrossRefPubMed
3.
Jones S, Zhang X, Parsons DW, Lin JC, Leary RJ, et al. Core signaling pathways in human pancreatic cancers revealed by global genomic analyses. Science. 2008;321:1801–6.CrossRefPubMedPubMedCentral
4.
Ariyama J, Suyama M, Satoh K, Sai J. Imaging of small pancreatic ductal adenocarcinoma. Pancreas. 1998;16:396–401.CrossRefPubMed
5.
Wasif N, Bentrem DJ, Farrell JJ, Ko CY, Hines OJ, et al. Invasive intraductal papillary mucinous neoplasm versus sporadic pancreatic adenocarcinoma: a stage-matched comparison of outcomes. Cancer. 2010;116:3369–77.CrossRefPubMedPubMedCentral
6.
Kuvshinoff BW, Bryer MP. Treatment of resectable and locally advanced pancreatic cancer. Cancer Control. 2000;7:428–36.PubMed
7.
Fusari M, Maurea S, Imbriaco M, Mollica C, Avitabile G, et al. Comparison between multislice CT and MR imaging in the diagnostic evaluation of patients with pancreatic masses. Radiol Med. 2010;115:453–66.CrossRefPubMed
8.
Tempero MA, Arnoletti JP, Behrman S, Ben-Josef E, Benson 3rd AB, et al. Pancreatic adenocarcinoma. J Natl Compr Canc Netw. 2010;8:972–1017.PubMedPubMedCentral
9.
Wong JC, Lu DS. Staging of pancreatic adenocarcinoma by imaging studies. Clin Gastroenterol Hepatol. 2008;6:1301–8.CrossRefPubMed
10.
Philip A, Ramchandani S, Dorrance K, Dorrance C. Sildenafil-induced thrombocytopenia. Ann Intern Med. 2008;149:437–9.CrossRefPubMed
11.
Yoshida T, Matsumoto T, Sasaki A, Shibata K, Aramaki M, et al. Outcome of paraaortic node-positive pancreatic head and bile duct adenocarcinoma. Am J Surg. 2004;187:736–40.CrossRefPubMed
12.
Sahani DV, Shah ZK, Catalano OA, Boland GW, Brugge WR. Radiology of pancreatic adenocarcinoma: current status of imaging. J Gastroenterol Hepatol. 2008;23:23–33.CrossRefPubMed
13.
Lee JG, Leung J. Tissue sampling at ERCP in suspected pancreatic cancer. Gastrointest Endosc Clin N Am. 1998;8:221–35.PubMed
14.
Miyata H, Kuwahara K, Sugiyama S, Iiboshi T, Serikawa M, et al. A case of pancreatic solid-pseudopapillary tumor without cystic component in an elderly man. Nihon Shokakibyo Gakkai Zasshi. 2006;103:1288–95.PubMed
15.
Hanninen EL, Ricke J, Amthauer H, Rottgen R, Bohmig M, et al. Magnetic resonance cholangiopancreatography: image quality, ductal morphology, and value of additional T2- and T1-weighted sequences for the assessment of suspected pancreatic cancer. Acta Radiol. 2005;46:117–25.CrossRefPubMed
16.
Park HS, Lee JM, Choi HK, Hong SH, Han JK, et al. Preoperative evaluation of pancreatic cancer: comparison of gadolinium-enhanced dynamic MRI with MR cholangiopancreatography versus MDCT. J Magn Reson Imaging. 2009;30:586–95.CrossRefPubMed
17.
Ohtsuka T, Ideno N, Aso T, Nagayoshi Y, Kono H, et al. Role of endoscopic retrograde pancreatography for early detection of pancreatic ductal adenocarcinoma concomitant with intraductal papillary mucinous neoplasm of the pancreas. J Hepatobiliary Pancreat Sci. 2013;20:356–61.CrossRefPubMed
18.
Krishna NB, Mehra M, Reddy AV, Agarwal B. EUS/EUS-FNA for suspected pancreatic cancer: influence of chronic pancreatitis and clinical presentation with or without obstructive jaundice on performance characteristics. Gastrointest Endosc. 2009;70:70–9.CrossRefPubMed
19.
Hasan MK, Hawes RH. EUS-guided FNA of solid pancreas tumors. Gastrointest Endosc Clin N Am. 2012;22:155–67. vii.CrossRefPubMed
20.
Kedia P, Gaidhane M, Kahaleh M. Technical advances in endoscopic ultrasound (EUS)-guided tissue acquisition for pancreatic cancers: how can we get the best results with EUS-guided fine needle aspiration? Clin Endosc. 2013;46:552–62.CrossRefPubMedPubMedCentral
21.
Chen J, Yang R, Lu Y, Xia Y, Zhou H. Diagnostic accuracy of endoscopic ultrasound-guided fine-needle aspiration for solid pancreatic lesion: a systematic review. J Cancer Res Clin Oncol. 2012;138:1433–41.CrossRefPubMed
22.
Salehimarzijarani B, Dadvar Z, Mousavi M, Mirsattari D, Zali MR, et al. Risk factors for post-ERCP cholangitis in patients with pancreatic cancer from a single referral center in Iran. Asian Pac J Cancer Prev. 2012;13:1539–41.CrossRefPubMed
23.
Dibble EH, Karantanis D, Mercier G, Peller PJ, Kachnic LA, et al. PET/CT of cancer patients: part 1, pancreatic neoplasms. AJR Am J Roentgenol. 2012;199:952–67.CrossRefPubMed
24.
Strobel O, Buchler MW. Pancreatic cancer: FDG-PET is not useful in early pancreatic cancer diagnosis. Nat Rev Gastroenterol Hepatol. 2013;10:203–5.CrossRefPubMed
25.
Tempero MA, Arnoletti JP, Behrman SW, Ben-Josef E, Benson 3rd AB, et al. Pancreatic adenocarcinoma, version 2.2012: featured updates to the NCCN Guidelines. J Natl Compr Canc Netw. 2012;10:703–13.PubMedPubMedCentral
26.
Luo G, Xiao Z, Long J, Liu Z, Liu L, et al. CA125 is superior to CA19-9 in predicting the resectability of pancreatic cancer. J Gastrointest Surg. 2013;17:2092–8.CrossRefPubMed
27.
van den Bosch RP, van Eijck CH, Mulder PG, Jeekel J. Serum CA19-9 determination in the management of pancreatic cancer. Hepatogastroenterology. 1996;43:710–3.PubMed
28.
Gui JC, Yan WL, Liu XD. CA19-9 and CA242 as tumor markers for the diagnosis of pancreatic cancer: a meta-analysis. Clin Exp Med. 2014;14:225–33.CrossRefPubMed
29.
Rothlin MA, Joller H, Largiader F. CA 242 is a new tumor marker for pancreatic cancer. Cancer. 1993;71:701–7.CrossRefPubMed
30.
Iacobuzio-Donahue CA, Maitra A, Shen-Ong GL, van Heek T, Ashfaq R, et al. Discovery of novel tumor markers of pancreatic cancer using global gene expression technology. Am J Pathol. 2002;160:1239–49.CrossRefPubMedPubMedCentral
31.
Li JJ, Li HY, Gu F. Diagnostic significance of serum osteopontin level for pancreatic cancer: a meta-analysis. Genet Test Mol Biomarkers. 2014;18:580–6.CrossRefPubMed
32.
Bunger S, Laubert T, Roblick UJ, Habermann JK. Serum biomarkers for improved diagnostic of pancreatic cancer: a current overview. J Cancer Res Clin Oncol. 2011;137:375–89.CrossRefPubMed
33.
Hidalgo M. Pancreatic cancer. N Engl J Med. 2010;362:1605–17.CrossRefPubMed
34.
Kondo H, Sugano K, Fukayama N, Hosokawa K, Ohkura H, et al. Detection of K-ras gene mutations at codon 12 in the pancreatic juice of patients with intraductal papillary mucinous tumors of the pancreas. Cancer. 1997;79:900–5.CrossRefPubMed
35.
Wolfgang CL, Herman JM, Laheru DA, Klein AP, Erdek MA, et al. Recent progress in pancreatic cancer. CA Cancer J Clin. 2013;63:318–48.CrossRefPubMedPubMedCentral
36.
Zhang J, Wang M, He S, Liu Y, Zhang B. The growth inhibitory effects by transfection of p16 gene on human pancreatic cancer cell line. Zhonghua Wai Ke Za Zhi. 2000;38:457–9.PubMed
37.
Zhang L, Gao J, Li L, Li Z, Du Y, et al. The neuronal pentraxin II gene (NPTX2) inhibit proliferation and invasion of pancreatic cancer cells in vitro. Mol Biol Rep. 2011;38:4903–11.CrossRefPubMed
38.
Sato N, Mizumoto K, Nagai E, Tanaka M. Telomerase as a new target for pancreatic cancer treatment. J Hepatobiliary Pancreat Surg. 2002;9:322–7.CrossRefPubMed
39.
Hong SH, Misek DE, Wang H, Puravs E, Giordano TJ, et al. An autoantibody-mediated immune response to calreticulin isoforms in pancreatic cancer. Cancer Res. 2004;64:5504–10.CrossRefPubMed
40.
Guo J, Wang W, Liao P, Lou W, Ji Y, et al. Identification of serum biomarkers for pancreatic adenocarcinoma by proteomic analysis. Cancer Sci. 2009;100:2292–301.CrossRefPubMed
41.
Qian JY, Mou SH, Liu CB. SELDI-TOF MS combined with magnetic beads for detecting serum protein biomarkers and establishment of a boosting decision tree model for diagnosis of pancreatic cancer. Asian Pac J Cancer Prev. 2012;13:1911–5.CrossRefPubMed
42.
Oettle H, Neuhaus P, Hochhaus A, Hartmann JT, Gellert K, et al. Adjuvant chemotherapy with gemcitabine and long-term outcomes among patients with resected pancreatic cancer: the CONKO-001 randomized trial. JAMA. 2013;310:1473–81.CrossRefPubMed
43.
Kawarada Y, Yokoi H, Isaji S, Naganuma T, Tabata M, et al. Modified standard pancreaticoduodenectomy for the treatment of pancreatic head cancer. Digestion. 1999;60 Suppl 1:120–5.CrossRefPubMed
44.
Malleo G, Marchegiani G, Salvia R, Butturini G, Pederzoli P, et al. Pancreaticoduodenectomy for pancreatic cancer: the Verona experience. Surg Today. 2011;41:463–70.CrossRefPubMed
45.
Evans DB, Farnell MB, Lillemoe KD, Vollmer Jr C, Strasberg SM, et al. Surgical treatment of resectable and borderline resectable pancreas cancer: expert consensus statement. Ann Surg Oncol. 2009;16:1736–44.CrossRefPubMed
46.
Takahashi H, Ohigashi H, Ishikawa O. Pancreaticoduodenectomy for invasive pancreatic cancer (with video). J Hepatobiliary Pancreat Sci. 2012;19:100–8.CrossRefPubMed
47.
Srinarmwong C, Luechakiettisak P, Prasitvilai W. Standard whipple’s operation versus pylorus preserving pancreaticoduodenectomy: a randomized controlled trial study. J Med Assoc Thai. 2008;91:693–8.PubMed
48.
Takahashi Y, Kaneoka Y, Maeda A, Isogai M. Distal pancreatectomy with celiac axis resection for carcinoma of the body and tail of the pancreas. World J Surg. 2011;35:2535–42.CrossRefPubMed
49.
Strasberg SM, Linehan DC, Hawkins WG. Radical antegrade modular pancreatosplenectomy procedure for adenocarcinoma of the body and tail of the pancreas: ability to obtain negative tangential margins. J Am Coll Surg. 2007;204:244–9.CrossRefPubMed
50.
Casadei R, Monari F, Buscemi S, Laterza M, Ricci C, et al. Total pancreatectomy: indications, operative technique, and results: a single centre experience and review of literature. Updates Surg. 2010;62:41–6.CrossRefPubMed
51.
Cunningham D, Chau I, Stocken DD, Valle JW, Smith D, et al. Phase III randomized comparison of gemcitabine versus gemcitabine plus capecitabine in patients with advanced pancreatic cancer. J Clin Oncol. 2009;27:5513–8.CrossRefPubMed
52.
Von Hoff DD, Ervin T, Arena FP, Chiorean EG, Infante J, et al. Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. N Engl J Med. 2013;369:1691–703.CrossRef
53.
Burris 3rd HA, Moore MJ, Andersen J, Green MR, Rothenberg ML, et al. Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer: a randomized trial. J Clin Oncol. 1997;15:2403–13.CrossRefPubMed
54.
Tempero M, Plunkett W, Ruiz Van Haperen V, Hainsworth J, Hochster H, et al. Randomized phase II comparison of dose-intense gemcitabine: thirty-minute infusion and fixed dose rate infusion in patients with pancreatic adenocarcinoma. J Clin Oncol. 2003;21:3402–8.CrossRefPubMed
55.
Louvet C, Labianca R, Hammel P, Lledo G, Zampino MG, et al. Gemcitabine in combination with oxaliplatin compared with gemcitabine alone in locally advanced or metastatic pancreatic cancer: results of a GERCOR and GISCAD phase III trial. J Clin Oncol. 2005;23:3509–16.CrossRefPubMed
56.
Heinemann V, Quietzsch D, Gieseler F, Gonnermann M, Schonekas H, et al. Randomized phase III trial of gemcitabine plus cisplatin compared with gemcitabine alone in advanced pancreatic cancer. J Clin Oncol. 2006;24:3946–52.CrossRefPubMed
57.
Bernhard J, Dietrich D, Scheithauer W, Gerber D, Bodoky G, et al. Clinical benefit and quality of life in patients with advanced pancreatic cancer receiving gemcitabine plus capecitabine versus gemcitabine alone: a randomized multicenter phase III clinical trial—SAKK 44/00-CECOG/PAN.1.3.001. J Clin Oncol. 2008;26:3695–701.CrossRefPubMed
58.
Moore MJ, Goldstein D, Hamm J, Figer A, Hecht JR, et al. Erlotinib plus gemcitabine compared with gemcitabine alone in patients with advanced pancreatic cancer: a phase III trial of the National Cancer Institute of Canada clinical trials group. J Clin Oncol. 2007;25:1960–6.CrossRefPubMed
59.
Xiong HQ, Varadhachary GR, Blais JC, Hess KR, Abbruzzese JL, et al. Phase 2 trial of oxaliplatin plus capecitabine (XELOX) as second-line therapy for patients with advanced pancreatic cancer. Cancer. 2008;113:2046–52.CrossRefPubMed
60.
Kulke MH, Blaszkowsky LS, Ryan DP, Clark JW, Meyerhardt JA, et al. Capecitabine plus erlotinib in gemcitabine-refractory advanced pancreatic cancer. J Clin Oncol. 2007;25:4787–92.CrossRefPubMed
61.
Homma H, Doi T, Mezawa S, Takada K, Kukitsu T, et al. A novel arterial infusion chemotherapy for the treatment of patients with advanced pancreatic carcinoma after vascular supply distribution via superselective embolization. Cancer. 2000;89:303–13.CrossRefPubMed
62.
Liao WC, Chien KL, Lin YL, Wu MS, Lin JT, et al. Adjuvant treatments for resected pancreatic adenocarcinoma: a systematic review and network meta-analysis. Lancet Oncol. 2013;14:1095–103.CrossRefPubMed
63.
Snady H, Bruckner H, Cooperman A, Paradiso J, Kiefer L. Survival advantage of combined chemoradiotherapy compared with resection as the initial treatment of patients with regional pancreatic carcinoma. An outcomes trial. Cancer. 2000;89:314–27.CrossRefPubMed
64.
Assifi MM, Lu X, Eibl G, Reber HA, Li G, et al. Neoadjuvant therapy in pancreatic adenocarcinoma: a meta-analysis of phase II trials. Surgery. 2011;150:466–73.CrossRefPubMedPubMedCentral
65.
Spry N, Harvey J, Macleod C, Borg M, Ngan SY, et al. 3D radiotherapy can be safely combined with sandwich systemic gemcitabine chemotherapy in the management of pancreatic cancer: factors influencing outcome. Int J Radiat Oncol Biol Phys. 2008;70:1438–46.CrossRefPubMed
66.
Wu W, Zhu F, Chang D, Wang J, Wang Y. Dosimetric comparison of treatment plans of pancreatic carcinoma treated with body gamma knife and tomotherapy. Zhongguo Yi Liao Qi Xie Za Zhi. 2013;37:232–4.PubMed
67.
Guo XZ, Cui ZM, Liu X. Current developments, problems and solutions in the non-surgical treatment of pancreatic cancer. World J Gastrointest Oncol. 2013;5:20–8.PubMedPubMedCentral
68.
Du Y, Jin Z, Meng H, Zou D, Chen J, et al. Long-term effect of gemcitabine-combined endoscopic ultrasonography-guided brachytherapy in pancreatic cancer. J Interv Gastroenterol. 2013;3:18–24.CrossRef
69.
Wang K, Chen Z, Meng Z, Lin J, Zhou Z, et al. Analgesic effect of high intensity focused ultrasound therapy for unresectable pancreatic cancer. Int J Hyperthermia. 2011;27:101–7.CrossRefPubMed
70.
Xie Q, Jia L, Liu YH, Wei CG. Synergetic anticancer effect of combined gemcitabine and photodynamic therapy on pancreatic cancer in vivo. World J Gastroenterol. 2009;15:737–41.CrossRefPubMedPubMedCentral
71.
Nicholson RI, Gee JM, Harper ME. EGFR and cancer prognosis. Eur J Cancer. 2001;37 Suppl 4:S9–15.CrossRefPubMed
72.
Strumberg D, Schultheis B, Scheulen ME, Hilger RA, Krauss J, et al. Phase II study of nimotuzumab, a humanized monoclonal anti-epidermal growth factor receptor (EGFR) antibody, in patients with locally advanced or metastatic pancreatic cancer. Invest New Drugs. 2012;30:1138–43.CrossRefPubMed
73.
Zhang Z, Wang J, Shen B, Peng C, Zheng M. The ABCC4 gene is a promising target for pancreatic cancer therapy. Gene. 2012;491:194–9.CrossRefPubMed
74.
Engelhardt K, Riley C, Cooke L, Mahadevan D. Monoclonal antibody therapies targeting pancreatic ductal adenocarcinoma. Curr Drug Discov Technol. 2006;3:231–43.CrossRefPubMed
75.
Takeda Y, Nakahira S, Katsura Y, Kagawa Y, Okishiro M, et al. Erlotinib plus gemcitabine combination therapy in patients with unresectable advanced pancreatic cancer—a single-institution experience. Gan To Kagaku Ryoho. 2013;40:1884–6.PubMed