Role of Serum and Bile Level of Pyruvate Kinase in Diagnosis of Malignant Biliary Obstruction: Article Review

Main Article Content

Mahmoud Abdel Samad Abdel Azeim ; Walid Ahmady Abd El-Dayem ; Talaat Fathy Aly ; Mohamed Ibrahim Magdy ; Atef Gouda Hussien


Malignant Biliary Obstruction; Diagnosis ; Pyruvate Kinase


Malignant biliary obstruction (MBO) presents both a diagnostic and therapeutic challenge. It is a common problem, with as many of 70% of pancreatic cancer patients presenting with obstruction upon diagnosis. Commonly, MBO appears as painless jaundice with anorexia and weight loss as the initial sign of disease such as in the classic presentation in pancreatic ductal adenocarcinoma or may occur during progression of malignancy. The presence of malignant biliary obstruction is typically associated with a poor 5-year survival rate of approximately 5%. Relief of the obstruction may lead to improved quality of life and extended survival. The determination of life expectancy is difficult and primarily dependent on the following factors including clinical status, metastatic disease, extent of local invasion, and use of palliative chemotherapy. Evidence supports a potential role of pyruvate kinase PKM2 in tumorigenesis. As an embryonic isoform, PKM2 is reactivated in tumors and overexpressed in multiple cancer types. Therefore, the aim of the present study was to review the significant role of pyruvate kinase in the diagnosis of malignant biliary obstruction

Abstract 27 | PDF Downloads 8


1- Gourgiotis, S., Kocher, H. M., Solaini, L., Yarollahi, A., Tsiambas, E., & Salemis, N. S. (2008). Gallbladder cancer. The American Journal of Surgery, 196(2), 252-264.‏
2- Albores‐Saavedra, J., Schwartz, A. M., Batich, K., & Henson, D. E. (2009). Cancers of the ampulla of vater: demographics, morphology, and survival based on 5,625 cases from the SEER program. Journal of surgical oncology, 100(7), 598-605.‏
3- Hennedige, T. P., Neo, W. T., & Venkatesh, S. K. (2014). Imaging of malignancies of the biliary tract-an update. Cancer imaging, 14(1), 1-21.‏
4- Alsowey, A. M., Salem, A. F., & Amin, M. I. (2021). Validity of MDCT cholangiography in differentiating benign and malignant biliary obstruction. Egyptian Journal of Radiology and Nuclear Medicine, 52(1), 1-16.‏
5- Fernandez Y Viesca, M., & Arvanitakis, M. (2019). Early diagnosis and management of malignant distal biliary obstruction: a review on current recommendations and guidelines. Clinical and Experimental Gastroenterology, 415-432.‏
6- Ventrucci, M., Cipolla, A., Racchini, C., Casadei, R., Simoni, P., & Gullo, L. (2004). Tumor M2-pyruvate kinase, a new metabolic marker for pancreatic cancer. Digestive diseases and sciences, 49, 1149-1155.‏
7- Xu, M. M., & Sethi, A. (2015). Diagnosing biliary malignancy. Gastrointestinal Endoscopy Clinics, 25(4), 677-690.‏
8- Navaneethan, U., Lourdusamy, V., Poptic, E., Hammel, J. P., Sanaka, M. R., & Parsi, M. A. (2015). Comparative effectiveness of pyruvate kinase M2 in bile, serum carbohydrate antigen 19-9, and biliary brushings in diagnosing malignant biliary strictures. Digestive Diseases and Sciences, 60, 903-909.‏
9- Dorrell, R., Pawa, S., Zhou, Y., Lalwani, N., & Pawa, R. (2020). The diagnostic dilemma of malignant biliary strictures. Diagnostics, 10(5), 337.‏
10- Goonetilleke, K. S., Mason, J. M., Siriwardana, P., King, N. K., France, M. W., & Siriwardena, A. K. (2007). Diagnostic and prognostic value of plasma tumor M2 pyruvate kinase in periampullary cancer: evidence for a novel biological marker of adverse prognosis. Pancreas, 34(3), 318-324.‏
11- Huguet, J. M., Lobo, M., Labrador, J. M., Boix, C., Albert, C., Ferrer-Barceló, L., ... & Sempere, J. (2019). Diagnostic-therapeutic management of bile duct cancer. World journal of clinical cases, 7(14), 1732.‏
12- Wang, W. Q., Liu, W., Zhang, N., Wang, P. H., Cao, J. Z., Chen, J. M., ... & He, X. D. (2018). The Diagnostic Value of Pyruvate Kinase Isoenzyme Type M2 for Biliary Tract Carcinoma. A Systematic Review and Meta-Analysis. Journal of Gastrointestinal & Liver Diseases, 27(1).‏
13- Dhar, D. K., Olde Damink, S. W., Brindley, J. H., Godfrey, A., Chapman, M. H., Sandanayake, N. S., ... & Pereira, S. P. (2013). Pyruvate kinase M2 is a novel diagnostic marker and predicts tumor progression in human biliary tract cancer. Cancer, 119(3), 575-585.‏
14- Mohandas, K. M., Swaroop, V. S., Gullar, S. U., Dave, U. R., Jagannath, P., & DeSouza, L. J. (1994). Diagnosis of malignant obstructive jaundice by bile cytology: results improved by dilating the bile duct strictures. Gastrointestinal endoscopy, 40(2), 150-154.
15- Bandara, I. A., Baltatzis, M., Sanyal, S., & Siriwardena, A. K. (2018). Evaluation of tumor M2-pyruvate kinase (Tumor M2-PK) as a biomarker for pancreatic cancer. World Journal of Surgical Oncology, 16(1), 1-6.‏
16- Singh, A., Gelrud, A., & Agarwal, B. (2015). Biliary strictures: diagnostic considerations and approach. Gastroenterology report, 3(1), 22-31.‏
17- ‏ Aguilar-Olivos, N. E., Oria-Hernández, J. A., Valdovinos-Andraca, F., Elizondo-Rivera, J., & Tellez-Avila, F. I. (2016). 119 Effectiveness of Biliary Pyruvate Kinase M2 for Diagnosis of Malignant Biliary Strictures: A Prospective and Comparative Study. Gastrointestinal Endoscopy, 83(5), AB125.‏
18- Wu, J., Hu, L., Chen, M., Cao, W., Chen, H., & He, T. (2016). Pyruvate kinase M2 overexpression and poor prognosis in solid tumors of digestive system: evidence from 16 cohort studies. OncoTargets and therapy, 4277-4288.‏
19- Budzynska, A., Nowakowska-Dulawa, E., Marek, T., & Hartleb, M. (2016). Serum and Bile Insulin-Like Growth Factor I, Interleukin-6 and Tumor M2-Pyruvate Kinase in Differentiation Malignant from Benign Biliary Strictures–Preliminary Report. Med Chem, 6, 429-434.‏
20- He, X., Du, S., Lei, T., Li, X., Liu, Y., Wang, H., ... & Wang, Y. (2017). PKM2 in carcinogenesis and oncotherapy. Oncotarget, 8(66), 110656.‏
21- Wong, N., Ojo, D., Yan, J., & Tang, D. (2015). PKM2 contributes to cancer metabolism. Cancer letters, 356(2), 184-191.‏
22- Azoitei, N., Becher, A., Steinestel, K., Rouhi, A., Diepold, K., Bobrovich, S., & Seufferlein, T. (2017). PKM2 promotes tumor angiogenesis by regulating HIF-1alpha through NF-kappaB activation. Cancer Research, 77(13_Supplement), 1809-1809.‏
23- Zhang, W., Zhang, X., Huang, S., Chen, J., Ding, P., Wang, Q., ... & Hu, W. (2021). FOXM1D potentiates PKM2‐mediated tumor glycolysis and angiogenesis. Molecular Oncology, 15(5), 1466-1485.‏
24- Suzuki, H., Komuta, M., Bolog, A., Yokobori, T., Wada, S., Araki, K., ... & Kuwano, H. (2015). Relationship between 18-F-fluoro-deoxy-D-glucose uptake and expression of glucose transporter 1 and pyruvate kinase M2 in intrahepatic cholangiocarcinoma. Digestive and Liver Disease, 47(7), 590-596.
25- Kumar, Y., Gurusamy, K., Pamecha, V., & Davidson, B. R. (2007). Tumor M2-pyruvate kinase as tumor marker in exocrine pancreatic cancer a meta-analysis. Pancreas, 35(2), 114-119.‏
26- Aloysius, M. M., Zaitoun, A. M., Bates, T. E., Albasri, A., Ilyas, M., Rowlands, B. J., & Lobo, D. N. (2009). Complete absence of M2-pyruvate kinase expression in benign pancreatic ductal epithelium and pancreaticobiliary and duodenal neoplasia. BMC cancer, 9(1), 1-8.‏
27- Chen, M., Liu, H., Li, Z., Ming, A. L., & Chen, H. (2021). Mechanism of PKM2 affecting cancer immunity and metabolism in Tumor Microenvironment. Journal of Cancer, 12(12), 3566.‏
28- Liu, W. R., Tian, M. X., Yang, L. X., Lin, Y. L., Jin, L., Ding, Z. B., ... & Shi, Y. H. (2015). PKM2 promotes metastasis by recruiting myeloid-derived suppressor cells and indicates poor prognosis for hepatocellular carcinoma. Oncotarget, 6(2), 846.‏
29- Xia, Y., Wang, X., Liu, Y., Shapiro, E., Lepor, H., Tang, M. S., ... & Wu, X. R. (2022). PKM2 is essential for bladder cancer growth and maintenance. Cancer research, 82(4), 571-585.‏
30- Qian, Z., Hu, W., Lv, Z., Liu, H., Chen, D., Wang, Y., ... & Zheng, S. (2020). PKM2 upregulation promotes malignancy and indicates poor prognosis for intrahepatic cholangiocarcinoma. Clinics and research in hepatology and gastroenterology, 44(2), 162-173.‏
31- Lu, W., Zhang, Y., Zhou, L., Wang, X., Mu, J., Jiang, L., ... & Liu, Y. (2016). miR-122 inhibits cancer cell malignancy by targeting PKM2 in gallbladder carcinoma. Tumor Biology, 37(12), 15615-15625.‏
32- Zhu, H., Luo, H., Zhu, X., Hu, X., Zheng, L., & Zhu, X. (2017). Pyruvate kinase M2 (PKM2) expression correlates with prognosis in solid cancers: a meta-analysis. Oncotarget, 8(1), 1628.‏