Latest News on Pancreatic Cancer : Jan 2022

Pancreatic cancer

Pancreatic cancer is a highly lethal disease, for which mortality closely parallels incidence. Most patients with pancreatic cancer remain asymptomatic until the disease reaches an advanced stage. There is no standard programme for screening patients at high risk of pancreatic cancer (eg, those with a family history of pancreatic cancer and chronic pancreatitis). Most pancreatic cancers arise from microscopic non-invasive epithelial proliferations within the pancreatic ducts, referred to as pancreatic intraepithelial neoplasias. There are four major driver genes for pancreatic cancer: KRAS, CDKN2A, TP53, and SMAD4. KRAS mutation and alterations in CDKN2A are early events in pancreatic tumorigenesis. Endoscopic ultrasonography and endoscopic ultrasonography-guided fine-needle aspiration offer high diagnostic ability for pancreatic cancer. Surgical resection is regarded as the only potentially curative treatment, and adjuvant chemotherapy with gemcitabine or S-1, an oral fluoropyrimidine derivative, is given after surgery. FOLFIRINOX (fluorouracil, folinic acid [leucovorin], irinotecan, and oxaliplatin) and gemcitabine plus nanoparticle albumin-bound paclitaxel (nab-paclitaxel) are the treatments of choice for patients who are not surgical candidates but have good performance status.[1]

Epidemiology of pancreatic cancer

Worldwide, over 200000 people die annually of pancreatic cancer. The highest incidence and mortality rates of pancreatic cancer are found in developed countries. In the United States, pancreatic cancer is the 4(th) leading cause of cancer death, and in Europe it is the 6th. Because of high fatality rates, pancreatic cancer incidence rates are almost equal to mortality rates. Pancreatic cancer is diagnosed late in the natural history of the disease, given the few early indicators of illness, and the lack of screening tests for this disease. Treatment has not improved substantially over the past few decades and has little effect on prolonging survival time. Therefore, prevention could play an important role in reducing pancreatic cancer mortality. International variations in rates and time trends suggest that environmental factors are likely to play a role in the etiology of pancreatic cancer. Variations in rates are substantial and occur even within industrialized nations. While rates have been stabilizing over the past 2 decades in many countries where they are already high, they continue to increase in countries where rates were relatively low 4 decades ago, such as Japan. In the US, the highest rates of pancreatic cancer incidence and mortality are observed among blacks, who have some of the highest rates in the world. A known cause of pancreatic cancer is tobacco smoking. This risk factor is likely to explain some of the international variations and gender differences. A number of studies observed a reduction in pancreatic cancer risk within a decade after smoking cessation, when compared to current smokers. With tobacco smoking as an exception, risk factors for pancreatic cancer are not well-established. Over the past 2 decades, epidemiological studies on pancreatic cancer have been plagued with methodological issues associated with studying a highly fatal disease, and inconsistent findings have hindered our understanding of the etiology of pancreatic cancer. Although familial pancreatic cancer is well-documented, the genes responsible for this condition have not been identified and are unlikely to explain more than 5-10% of all pancreatic cancer cases. Chronic pancreatitis and diabetes mellitus are medical conditions that have been consistently related to pancreatic cancer. Data from numerous studies suggest that these conditions are likely to be causally related to pancreatic cancer, rather than being consequences of the cancer. Recent cohort studies, which are less prone to biases than case-control studies, suggest that obesity increases the risk of pancreatic cancer. Other studies support the hypothesis that glucose intolerance and hyperinsulinemia are important in the development of pancreatic cancer. Other potential risk factors include physical inactivity, aspirin use, occupational exposure to certain pesticides, and dietary factors such as carbohydrate or sugar intake.[2]

Epidemiology of pancreatic cancer

Cancer of the pancreas remains one of the deadliest cancer types. Based on the GLOBOCAN 2012 estimates, pancreatic cancer causes more than 331000 deaths per year, ranking as the seventh leading cause of cancer death in both sexes together. Globally, about 338000 people had pancreatic cancer in 2012, making it the 11th most common cancer. The highest incidence and mortality rates of pancreatic cancer are found in developed countries. Trends for pancreatic cancer incidence and mortality varied considerably in the world. A known cause of pancreatic cancer is tobacco smoking. This risk factor is likely to explain some of the international variations and gender differences. The overall five-year survival rate is about 6% (ranges from 2% to 9%), but this vary very small between developed and developing countries. To date, the causes of pancreatic cancer are still insufficiently known, although certain risk factors have been identified, such as smoking, obesity, genetics, diabetes, diet, inactivity. There are no current screening recommendations for pancreatic cancer, so primary prevention is of utmost importance. A better understanding of the etiology and identifying the risk factors is essential for the primary prevention of this disease.[3]

Identification of Candidate Biomarkers and Cancer Genes AHNAK2 and EPPK1 in Pancreatic Cancer

Aims: The lack of specific symptoms at early tumor stages, together with a high biological aggressiveness of the tumor contribute to the high mortality rate for pancreatic cancer (PC). Improved screening for earlier diagnosis, through the detection of diagnostic and prognostic biomarkers provides the best hope of increasing the rate of curatively resectable carcinomas. The aim of this study is to provide new targets for use as biomarkers in PC.

Study Design: In a previous study, we identified novel candidate cancer genes and biomarkers that were significantly upregulated in PC, through a meta-analysis of large number of microarray datasets, using bioinformatics methods.  In this study, we analyzed the expression of these genes in a panel of pancreatic cancer cell lines by quantitative Reverse Transcription-PCR (qRT-PCR).

Place and Duration of Study: Department of Chemistry and Biochemistry and Department of Biology, University of Northern Iowa, USA, between June 2014 and Dec 2015.

Methodology: We analyzed the expression of three genes, AHNAK2, EPPK1 and IGHG3 in a panel of seven standard PC cell lines, AsPC-1, BxPC-3, Capan-2, CFPAC-1, HPAF-II, PANC-1, and SW 1990 by Relative Quantification. qRT-PCR experiments were conducted in triplicate, and each experiment was replicated twice using different passages.

Results: AHNAK2 was significantly upregulated in all PC cell lines tested, with P values < 0.005 except for PANC-1 (P < 0.05). EPPK1 too was significantly upregulated (P < 0.05) in six of seven PC cell lines tested. While IGHG3 was nominally upregulated in all PC cell lines, upregulation was significant (P < 0.05) in only four PC cell lines.

Conclusion: Our results confirm that AHNAK2 and EPPK1 are novel candidates for use as biomarkers in pancreatic cancer. IGHG3 does not appear to be a suitable candidate, due to its low levels of expression in both PC and control cell lines.[4]

A Rare Case Report of a Metastatic Tumor of the Spermatic Cord Arising from Pancreatic Cancer

A 60-year-old patient complaining of pain and elevation of the right scrotal contents, who had been treated for pancreatic cancer, was suspected of having spermatic cord tumor. He underwent high orchiectomy for pain management and pathological diagnosis. The tumor was a metastatic adenocarcinoma from pancreatic cancer. Pancreatic cancer accompanied by spermatic cord metastasis is extremely rare. In patients with a mass in the spermatic cord and a history of neoplasm, the possibility of metastasis from the primary cancer should be considered.[5]

Reference

[1] Kamisawa, T., Wood, L.D., Itoi, T. and Takaori, K., 2016. Pancreatic cancer. The Lancet, 388(10039), pp.73-85.

[2] Michaud, D., 2004. Epidemiology of pancreatic cancer. Minerva chirurgica, 59(2), pp.99-111.

[3] Ilic, M. and Ilic, I., 2016. Epidemiology of pancreatic cancer. World journal of gastroenterology, 22(44), p.9694.

[4] Smith, A., Poole, L., Dhanwada, K. and Goonesekere, N.C., 2016. Identification of candidate biomarkers and cancer genes AHNAK2 and EPPK1 in pancreatic cancer. Journal of Advances in Medicine and Medical Research, pp.1-8.

[5] Sato, R., Watanabe, D., Imagawa, M., Okamoto, M., Fukuzawa, K. and Yonemasu, H., 2017. A Rare Case Report of a Metastatic Tumor of the Spermatic Cord Arising from Pancreatic Cancer. Journal of Cancer and Tumor International, pp.1-4.

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