Tumor markers: an important adjunct to clinical practice.

  "Medicine is a science of uncertainty and an art of probability."
--Sir William Osler

The authors of the article, "Elevated CA 19-9 Levels in a Patient with Mirizzi Syndrome: Case Report" (1) provide a unique scenario in which a person presents with an elevated serum carbohydrate antigen 19-9 (CA 19-9). The initial workup involved looking for typical causes such as biliary and ampullary carcinoma, but ultimately revealed a case of Mirizzi syndrome. While this is not the first report, (2,3) this case reminds us that often in medicine one needs to think outside of the box. Occasionally, we forget that diagnoses do not always have to be defined by lab tests, and this case report shows us that although they are helpful, tumor markers are not always accurate. Also, it highlights the potential benefit of newer imaging modalities.

Tumor markers such as CA 19-9 are increasingly becoming important to the practice of medicine. They help in making diagnoses, assessing prognoses, and assisting in determining responses to therapy. It is well documented that certain tumor markers such as HER-2 in advanced breast cancer, and hCG for nonseminomatous germ cell tumors, can be used as criterion for clinical decision making. However, not all tumor markers can be used in this fashion. (4)

CA 19-9 is a commonly used serum tumor marker to help solidify the diagnosis of cancer of the biliary system or pancreas, as well as other organ systems. It carries a sensitivity of 70 to 80% in pancreatic cancer and 60 to 70% in biliary cancer. (1,5,6) As the authors correctly pointed out, the CA 19-9 can also be elevated in cases of cirrhosis, cholangitis or acute liver injury. This case shows very clearly how one needs to consider benign entities in the differential of biliary obstruction with high CA 19-9. As with any tumor marker it should be used to guide a diagnosis as opposed to making the diagnosis.

Yip et al provided us with an interesting case in which they evaluated cholecystectomies; 28% of those with Mirizzi syndrome had a gallbladder cancer as opposed to 2% without Mirizzi. While this may lead us to believe that there is an association with the syndrome and cancer, there have been no large trials to back this up. Highlighting the lack of reliability in this situation.

As illustrated by this case, diagnosis before surgery is sometimes very difficult. New technologies such as conventional endoscopic ultrasound and intraductal ultrasound can represent options to be considered in similar situations. (7) These procedures may be beneficial in cases similar to the one described by the authors.

The case by Sanchez et al reminds us that medicine is indeed "a science of uncertainty" and that tumor markers such as CA 19-9, are often helpful but not diagnostic.

References

1. Sanchez M, Gomes H, Marcus EN. Elevated CA 19-9 Levels in a Patient with Mirizzi's Syndrome: Case Report. South Med J 2006;99:160-163.

2. Lee KC, Yamazaki O, Horii K, et al. Mirizzi syndrome caused by xanthogranulomatous cholecystitis: report of a case. Surg Today 1997;27:757-761.

3. Principe A, Del Gaudio M, Grazi GL, et al. Mirizzi syndrome with cholecysto-choledocal fistula with a high CA19-9 level mimicking biliary malignancies: a case report. Hepatogastroenterology 2003;50:1259-1262.

4. Duffy MJ. Evidence for the clinical use of tumour markers. Ann Clin Biochem 2004;41(Pt 5):370-377.

5. Pleskow DK, Berger HJ, Gyves J, et al. Evaluation of a serologic marker, CA 19-9, in the diagnosis of pancreatic cancer [see comment]. Ann Intern Med 1989;110:704-709.

6. Pavai S, Yap SF. The clinical significance of elevated levels of serum CA 19-9. Med J Malaysia 2003;58:667-672.

7. Moon JH, Cho YD, Cheon YK, et al. Wire-guided intraductal US in the assessment of bile duct strictures with Mirizzi syndrome-like features at ERCP. Gastrointest Endosc 2002;56:873-879.

Mankanwal S. Sachdev, MD, and Claudio R. Tombazzi, MD

From the Department of Gastroenterology, University of Tennessee, Memphis, TN.

Reprint requests to Mankanwal S. Sachdev, MD, Assistant Professor of Medicine, Department of Internal Medicine, Division of Gastroenterology, University of Tennessee, 920 Madison, Suite 240, Memphis, TN 38163. Email: [e-mail]

Accepted October 25, 2005.