Occult tumor cells in lymph nodes as a predictor for tumor relapse in pancreatic adenocarcinoma.
OBJECTIVE
Occurrence of tumor relapse is frequent in patients with pancreatic cancer despite the absence of residual tumor detectable at primary surgery and in histopathological examination. Therefore, it has to be assumed that current tumor staging procedures fail to identify minimal amounts of disseminated tumor cells, which might be precursors of subsequent metastatic relapse. The aim of this study was to assess the prognostic impact of minimal tumor cell spread detected in lymph nodes classified as "tumor-free" in routine histopathologic evaluation.


METHODS
A total of 154 "tumor-free" lymph nodes from 59 patients with pancreatic cancer who underwent intentionally curative tumor resection were examined by immunohistochemistry for disseminated tumor cells.


RESULTS
Fifty (32.5%) of the "tumor-free" lymph nodes obtained from 36 (61%) patients displayed disseminated tumor cells. Multivariate survival analysis revealed that the presence of disseminated tumor cells in "tumor-free" lymph nodes is an independent prognostic factor for both a significantly reduced relapse-free survival (p = 0.03) and overall survival (p = 0.02).


CONCLUSIONS
The frequent occurrence and prognostic impact of immunohistochemically identifiable disseminated tumor cells in lymph nodes of patients with operable pancreatic cancer supports the need for a refined staging system of excised lymph nodes, which should include immunohistochemical examination.
Scheunemann
Peter
P
Department of General Surgery, Heinrich-Heine University, University Hospital Düsseldorf, Düsseldorf, Germany. scheunemann@med.uni-duesseldorf.de
Stoecklein
Nikolas H
NH
Rehders
Alexander
A
Bidde
Minu
M
Metz
Sylvia
S
Peiper
Matthias
M
Eisenberger
Claus F
CF
Schulte Am Esch
Jan
J
Knoefel
Wolfram T
WT
Hosch
Stefan B
SB
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D021441:Carcinoma, Pancreatic Ductal / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008197:Lymph Node Excision; D008198:Lymph Nodes / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D010180:Pancreatectomy; D010190:Pancreatic Neoplasms / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D011379:Prognosis
Cancer. 1999 Feb 15;85(4):769-78
10091753
J Gastrointest Surg. 1999 Sep-Oct;3(5):468-76
10482702
Eur J Surg Oncol. 1991 Apr;17(2):173-81
2015922
Pancreas. 1997 Aug;15(2):154-9
9260200
Surgery. 2000 Jan;127(1):40-6
10660757
N Engl J Med. 1998 Jul 23;339(4):264-5
9673307
J Clin Oncol. 1997 Jul;15(7):2701-8
9215843
Hepatogastroenterology. 2004 May-Jun;51(57):862-8
15143935
Arch Surg. 2004 Jul;139(7):718-25; discussion 725-7
15249403
J Am Coll Surg. 1995 Dec;181(6):483-503
7582222
Proc Natl Acad Sci U S A. 2003 Jun 24;100(13):7737-42
12808139
J Clin Oncol. 1998 Aug;16(8):2632-40
9704713
Semin Cancer Biol. 2001 Oct;11(5):327-37
11562175
Br J Surg. 1995 Dec;82(12):1686-91
8548242
Cancer. 1978 Oct;42(4):2025-31
213191
Dig Surg. 1999;16(4):297-304
10449974
Br J Cancer. 1999 Nov;81(5):870-3
10555760
J Clin Oncol. 1994 Apr;12(4):725-9
7512130
Am J Surg. 1991 Feb;161(2):219-25
1990875
Br J Cancer. 2000 Jan;82(2):429-35
10646900
J Surg Oncol. 1998 Mar;67(3):194-202
9530893
Cancer. 1998 Sep 1;83(5):858-66
9731887
Am J Pathol. 1999 Jan;154(1):83-95
9916922
Ann Surg Oncol. 2001 Oct;8(9 Suppl):18S-21S
11599890
Oncology. 2000;58(1):38-44
10644939
Br J Surg. 1992 Feb;79(2):152-5
1348201
J Natl Cancer Inst. 1999 Jul 7;91(13):1113-24
10393719
Lancet. 2002 Aug 31;360(9334):683-9
12241875
J Natl Cancer Inst. 1993 Sep 1;85(17):1419-24
7688814
Nat Biotechnol. 1998 Aug;16(8):737-42
9702771
Cancer Res. 1995 Aug 1;55(15):3417-20
7542169
Proc Natl Acad Sci U S A. 1999 Apr 13;96(8):4494-9
10200290
Cancer. 1961 Nov-Dec;14:1266-71
14486400
N Engl J Med. 1998 Jul 23;339(4):223-8
9673300
J Clin Oncol. 1994 Sep;12(9):1827-32
8083707
Differentiation. 1987;36(2):145-63
2452110
Ann Surg. 2004 Dec;240(6):993-1000; discussion 1000-1
15570205
Acta Oncol. 1988;27(5):483-7
3060155
J Clin Oncol. 1999 Jan;17 (1):19-24
10458213
Cancer Res. 2000 Dec 15;60(24):6836-40
11156375
J Clin Pathol. 1990 Mar;43(3):213-9
1692040
Science. 1997 Nov 7;278(5340):1054-9
9353179
Clin Cancer Res. 1998 Sep;4(9):2141-6
9748132
N Engl J Med. 1997 Oct 23;337(17):1188-94
9337377
Cancer. 1994 Feb 1;73(3):563-9
7507795
Br J Cancer. 1987 Dec;56(6):838-9
3435709
J Urol. 2000 Aug;164(2):532-6
10893639
World J Surg. 1995 May-Jun;19(3):410-4; discussion 414-5
7638998
Lancet. 1990 Jun 30;335(8705):1565-8
1972494
Cancer Lett. 2000 May 29;153(1-2):189-97
10779649
Langenbecks Arch Surg. 2005 Apr;390(2):94-103
15578211