Re: CA 19-9 in potentially resectable pancreatic cancer: perspective to adjust surgical and preoperative therapy.

I am really not a pessimist, but several concepts continue to surround the surgical management of pancreatic adenocarcinoma: (1) despite improvements in radiologic technology, a significant fraction of patients are still found to have unresectable disease in the operating room, (2) despite improvements in perioperative care and team-based patient management, a significant fraction of patients develop complications of surgical resection that may lead to immediate death, delayed death, or dramatically decreased quality of life, (3) the vast majority of patients will die from recurrent disease despite a a curativea resection, and (4) improvements in adjuvant therapy have lagged behind the treatment of other solid organ malignancies and offer only small improvements in median survival. If I were a pessimist, I would never operate on these patients, but instead I continue to hold out hope that each patient may be that uncommon 5or 10-year survivor following surgical resection of pancreatic cancer. Nearly a decade has passed since the association of carbohydrate antigen (CA) 19-9 with some aspect of the biology of pancreatic cancer was first reported. Since that time, various roles of CA 19-9 in the management of patients with pancreatic adenocarcinoma have been described including the differentiation of benign from malignant pancreatic disease, prediction of resectable disease, identification of patients for selective staging laparoscopy, the identification of patients at risk for early recurrence and death following potentially curative resection, and for use in the surveillance for disease recurrence. Yet for each of these aspects, the specific role of CA 19-9 is only part of clinical assessment and decision making in these patients. Before beginning the discussion, it is critical to understand what CA 19-9 is and how it can be used as a a tumor marker.a CA 19-9 was first identified following the screening patient sera by hybridoma-derived monoclonal antibodies. One such antibody, 1116 NS 19-9 developed by Koprowski et al., 3 was shown to react with a sialylated lacto-N-fucopentaose II, which was present in high levels in sera of patients with colon, gastric, and pancreatic cancer. Based on the screening of a variety of tumors by immunohistochemical methods as well as sera from patients with a variety of gastrointestinal and gynecologic cancers, CA 19-9 was felt to be specific for malignancy and termed a a tumor markera . In screening sera from more than 1,000 blood donors, CA 19-9 was found to be undetectable ino~8o%, and waso\37 U/ml in all but six samples, hence the threshold value of 37 U/ml for a normala . Yet 4o% of a parallel study population of patients with benign disease (such as inflammatory bowel disease, pancreatitis, or gastrointestinal polyps) had CA 19-9 levelso [37 U/ml. Thus, CA 19-9 is not a perfect tumor marker in terms of sensitivity (79o% for pancreatic adenocarcinoma, 50o% for gastric carcinoma, and 46o% for advanced colorectal carcinoma) and specificity (98.5o%). However, it is pretty good when compared with other tumor markers such as CEA, alphafetoprotein or CA 125. There are three important limitations of CA 19-9 that must be recognized as they are critical to the implementation in patients with suspected pancreatic cancer. The first is that CA 19-9 is a sialylated Lewis (a) antigen, which is normally expressed on the surface of erythrocytes. Up to 10o% of the white population will not express any detectable level of CA 19-9 because of absence of fucosyltransferase, one of the enzymes involved in the biosynthesis. Therefore, in up to 10o% of patients with pancreatic adenocarcinoma, CA 19-9 will be undetectable and therefore of no utility in any aspect of clinical decision making. The second aspect relates to the lack of perfect specificity in which patients with benign disease can have Society of Surgical Oncology 2013