Send letter to journal:
Re: Reply to Harlozinska-Szmirka et al

Dear Editor

In response to the letter addressed by Dr Harlozinska-Szmyrka we agree with the remarks made in relation to the difficulties in discrimination between chronic pancreatitis and adenocarcinoma using currently employed diagnostic imaging and tumour marker analysis. Our study aimed at determining risk of cancer development in patients with proven chronic pancreatitis,[1] examining age and sex standardised incidence ratios calculated from the number of observed cases of pancreatic cancer in our cohort of 373 patients with predominantly alcohol-related chronic pancreatitis to the number of cases expected in the National Cancer Registry. Our study design did not take into consideration diagnostic dilemmas and focused purely on cancer risk in our cohort or patients using the defined stringent criteria. Indeed, we previously underlined the interest of biological markers in this situation e.g. CA19-9 and circulating K-ras;[2,3] however these markers have problems with both sensitivity and specificity. We acknowledge that given the difficulties in diagnosing cancer in this situation, the establishment of new tumor markers such as tissue polypeptide specific antigen (TPS) [4] with proven good sensitivity and specificity should provide for progress in the future. Is has to be stressed however, that TPS, a marker of proliferation activity, is not specific to pancreatic cancer and other digestive and non -digestive cancers as well as benign chronic disorders may have high levels of this marker.[5-7] Thus, validated data concerning tumour markers, either alone or in combination, in distinguishing pancreatic cancer from chronic pancreatitis should prove important in diagnostic situations.

References

(1) Malka D, Hammel P, Maire F, et al. Risk of pancreatic adenocarcinoma in chronic pancreatitis. Gut 2002;51:849-52.

(2) Nouts A, Levy P, Voitot H, et al. Diagnostic value of serum Ca 19-9 antigen in chronic pancreatitis and pancreatic adenocarcinoma. Gastroenterol Clin Biol 1998;22:152-9.

(3) Maire F, Micard S, Hammel P, et al. Differential diagnosis between chronic pancreatitis and pancreatic cancer: value of the detection of KRAS2 mutations in circulating DNA. Br J Cancer 2002 27;87:551-4.

(4) Slesak B, Harlozinska-Szmyrka A, Knast W et al. Tissue polypeptide specific antigen (TPS), a marker for differentiation between pancreatic carcinoma and chronic pancreatitis. A comparative study with CA 19-9. Cancer 2000;89:83-8.

(5) Malamitsi-Puchner A, Vazeou-Gerasimidi A, Sarandakou A et al. Tissue polypeptide-specific antigen serum concentrations in children, adolescents, and young adults with type 1 diabetes. Diabetes Care 2002;25:240-1.

(6) Hrycek A, Kokocinska D, Kosmider J, et al. Tissue-polypeptide-specific antigen in SLE patients treated with low doses of quinagolide. Lupus 2003;12:149-52.

(7) Valik D, Nekulova M. Serum tissue polypeptide-specific antigen (TPS): what is its diagnostic value? Br J Cancer 2000;82:1756-8.

Send letter to journal:
Re: The diagnostic dilemmas in discrimination between pancreatic carcinoma and chronic pancreatitis

Dear Editor

Early diagnosis to distinguish between malignant pancreatic tumor and chronic pancreatitis is still difficult despite significant progress in imaging techniques. Moreover the patients with chronic pancreatitis are in a higher risk of pancreatic cancer development.

The recently published study performed by Malka et al.[1] clearly confirms these difficulties independently of rigorous selection criteria of patients with chronic pancreatitis. To exclude the possibility that chronic pancreatitis may be caused by early potentially premalignant lesions, the authors eliminated from their investigations even the patients with chronic pancreatitis in whom pancreatic cancer was recognized during the first 2 years of follow-up.

Several studies indicate the value of circulating tumor markers evaluation as a simple, sensitive and reliable tests facilitating the differential diagnosis between chronic pancreatitis and cancer.[2-8] To improve the effectiveness of serological diagnosis of patients with pancreatic carcinoma different tumor markers have been assessed including CEA, CA 242, CA 50, CA 72-4.[2-5,8] However, the sensitivity and specificity of these markers appeared to be insufficient for the differentiation of pancreatic carcinoma and chronic pancreatitis. In 1996 CAM 17-1 [6] was described as a new useful diagnostic marker in pancreatic carcinoma. It showed a sensitivity similar to that of CA 19-9 but higher specificity, giving only 10% false positive results in patients with chronic pancreatitis.

Tissue polypeptide specific antigen (TPS) is a different type of antigen that does not correlate with tumor mass but reflects the tumor proliferative activity.[9] Our study [7] revealed that the elevated levels of TPS detected preoperatively 100% of patients with pancreatic carcinoma. The introduction of 200 U/L as a decision criterion for TPS level allowed to increase the specificity of this marker to 98% and eliminated all but 2% of the false positive results in patients with chronic pancreatitis. Moreover, the TPS is useful for detection of early stages of clinical advancement of pancreatic carcinoma.

It seems to be that measurement of TPS, using 200 U/L as its cut off value should facilitate the more precise discrimination between early stages of pancreatic carcinoma and chronic pancreatitis.

References

(1) Malka D, Hammel P, Maire F, et al. Risk of pancreatic adenocarcinoma in chronic pancreatitis. Gut 2002;51:849-52.

(2) Banfi G, Zerbi A, Pastori S, et al. Behavior of tumor markers CA 19-9, CA 195, CAM 43, CA 242 and TPS in diagnosis and follow-up of pancreatic cancer. Clin Chem 1993;39:420-3.

(3) Ventrucci M, Ubalducci GM, Cipolla A, et al. Serum CA 242: the search for a valid marker of pancreatic cancer. Clin Chem Lab Med 1998;36:179-84.

(4) Kawa S, Tokoo M, Hasebe O, et al. Comparative study of CA 242 and CA 19 -9 for the diagnosis of pancreatic cancer. Br J Cancer 1994;70:481-6.

(5) Sperti C, Pasquali C, Guolo P, et al. Serum tumor markers and cyst fluid analysis are useful for the diagnosis of pancreatic cystic tumors. Cancer 1996;78:237-43.

(6) Gansauge F, Gansauge S, Parker N, et al. CAM 17-1 – A new diagnostic marker in pancreatic cancer. Br J Cancer 1996;74:1997-2002.

(7) Slesak B, Harlozinska-Szmyrka A, Knast W, et al. Tissue polypeptide specific antigen (TPS), a marker for differentiation between pancreatic carcinoma and chronic pancreatitis. Cancer 2000;89:83-8.

(8) Pasanen PA, Eskelinen M, Partanen K, et al. Diagnostic value of tissue polypeptide specific antigen in patients with pancreatic carcinoma. Tumor Biol 1994;15:52-60.

(9) Rydlander L, Ziegler E, Bergman T, et al. Molecular characterization of tissue-polypeptide-specific-antigen epitope and its relationship to human cytokeratin 18. Eur J Biochem 1996;241:309-14.