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Combined use of nuclear morphometry and DNA ploidy as prognostic indicators in nonresectable adenocarcinoma of the pancreas

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Summary

The introduction of combined modality treatment has only marginally affected the prognosis in nonresectable pancreatic carcinoma. Evaluation of easily, accessible prognostic variables could be of clinical importance when selecting patients for proper therapy. DNA ploidy and morphometric variables were chosen as prognostic markers and assessed on cytologic material obtained by fine-needle aspiration biopsy (FNAB) from 128 patients with pancreatic carcinoma. The nuclear DNA content was measured by image cytometry. Patients were categorized as short-term, (≤6 mo) and long-term survivors (>6 mo). Ninety-eight of 116 nonresectable patients were possible to evaluate. There were significant differences between short- and long-term survivors with regard to DNA ploidy (p<0.01) and the morphonuclear variable anisokaryosis (p<0.001). In patients with either DNA aneuploid tumors or anisokaryosis ≥0.6, the survival time was 6 mo or less in 85 and 93%, respectively. When both these criteria were fulfilled, only 5% survived for more than 6 mo. Thus, DNA ploidy and morphometry, separately or in combination, may provide prognostic information in nonresectable pancreatic carcinoma.

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References

  1. Gudjonsson B. Cancer of the pancreas. 50 years of surgery.Cancer 1987; 60: 2284–2303.

    Article  PubMed  CAS  Google Scholar 

  2. Kalser MH, Barkin J, MacIntyre JM. Pancreatic cancer. Assessment of prognosis by clinical presentation.Cancer 1985; 56: 397–402.

    Article  PubMed  CAS  Google Scholar 

  3. Klinkenbijl JHG, Jeekel J, Schmitz PIM, Rombout PA, Nix GA, Bruining HA, van Blankenstein M. Carcinoma of the pancreas and periampullary region: palliation versus cure.Br J Surg 1993; 80: 1575–1578.

    Article  PubMed  CAS  Google Scholar 

  4. Lundin J, Roberts PJ, Kuusela P, Haglund C. The prognostic value of preoperative serum levels of CA 19-9 and CEA in patients with pancreatic cancer.Br J Cancer 1994; 69: 515–519.

    PubMed  CAS  Google Scholar 

  5. Dunn E. The impact of technology and improved perioperative management upon survival from carcinoma of the pancreas.Surg Gynecol Obstet 1987; 164: 237–244.

    PubMed  CAS  Google Scholar 

  6. Warshaw AL, Swanson RS. Pancreatic cancer in 1988. Possibilities and probabilities.Ann Surg 1988; 208: 541–553.

    Article  PubMed  CAS  Google Scholar 

  7. Evans DB, Termuhlen PM, Byrd DR, Ames FC, Ochran TG, Rich TA. Intraoperative radiation therapy following pancreaticoduodenectomy.Ann Surg 1993; 218: 54–60.

    Article  PubMed  CAS  Google Scholar 

  8. Bruckner HW, Crown J, McKenna A, Hart R. Leucovorin and 5-Fluorouracil as a treatment for disseminated cancer of the pancreas and unknown primary tumors.Cancer Res 1988; 48: 5570–5572.

    PubMed  CAS  Google Scholar 

  9. Lygidakis NJ, Savanis G, Toloupakis E, Katsikoyannis N, Kapenanukis A, Pothoulakis J, Maganas D, Papadimitriou A, Butziotis N, Zisimopoulos A. Induced in vivo targeted transarterial and transvenous immuno-stimulation in patients with unresectable pancreatic carcinoma.Hepatogastroenterology 1993; 40: 574–581.

    PubMed  CAS  Google Scholar 

  10. Eskelinen M, Lipponen P. A review of prognostic factors in human pancreatic adenocarcinoma.Cancer Detect Prev 1992; 16: 287–295.

    PubMed  CAS  Google Scholar 

  11. Weger AR, Lindholm J, Glaser K, Mairinger T, Mikuz G. Morphometry and prognosis in cancer of the pancreatic head.Pathol Res Pract 1992; 188: 764–769.

    PubMed  CAS  Google Scholar 

  12. Ceuterick M, Gelin M, Rickaert F, van de Stadt J, Devière J, Cremer M, Lambilliotte JP. Pancreaticoduodenal resection for pancreatic or periampullary tumors—a ten-year experience.Hepatogastroenterology 1989; 36: 467–473.

    PubMed  CAS  Google Scholar 

  13. Weger A-R, Falkmer UG, Schwab G, Glaser K, Kemmler G, Bodner E, Auer GU, Mikuz G. Nuclear DNA distribution pattern of the parenchymal cells in adenocarcinomas of the pancreas and in chronic pancreatitis. A study of archival specimens using both image and flow cytometry.Gastroenterology 1990; 99: 237–242.

    PubMed  CAS  Google Scholar 

  14. Herrera MF, van Heerden JA, Katzmann JA, Weiland LH, Nagorney DM, Ilstrup D. Evaluation of DNA nuclear pattern as a prognostic determinant in resected pancreatic ductal adenocarcinoma.Ann Surg 1992; 215: 120–124.

    Article  PubMed  CAS  Google Scholar 

  15. Allison DC, Bose KK, Hruban RH, Piantadosi S, Dooley WC, Boitnott JK, Cameron JL. Pancreatic cancer cell DNA content correlates with long-term survival after pancreatoduodenectomy.Ann Surg 1991; 214: 648–656.

    Article  PubMed  CAS  Google Scholar 

  16. Richaert F, Gelin M, van Gansbeke D, Lambilliotte JP, Verhest A, Pasteels JL, Klöppel G, Kiss R, Computerized morphonuclear characteristics and DNA content of adenocarcinoma of the pancreas, chronic pancreatitis, and normal tissues: Relationship with histopathologic grading.Hum Pathol 1992; 23: 1210–1215.

    Article  Google Scholar 

  17. Lipponen PK, Eskelinen MJ, Collan Y, Marin S, Alhava E. Volume-corrected mitotic index in human pancreatic cancer. Relation to histologic grade, clinical stage, and prognosis.Scand J Gastroenterol 1990; 25: 548–554.

    Article  PubMed  CAS  Google Scholar 

  18. Mäkinen K, Eskelinen M, Lipponen P, Nuutinen P, Marin S, Alhava E. Ag-NORs related to flow cytometry, morphometry and prognosis in patients with pancreatic cancer.Anticancer Res 1993; 13: 157–160.

    PubMed  Google Scholar 

  19. Weger A-R, Lindholm J. Discrimination of pancreatic adenocarcinomas from chronic pancreatitis by morphometric analyses.Pathol Res Pract 1992; 188: 44–48.

    PubMed  CAS  Google Scholar 

  20. Killough BW, Nichols CA, Nicholson JA, Gansler TS. Diagnosis of pancreatic carcinoma by fine needle aspiration cytology and computerized cytomorphometry.Anal Quant Cytol Histol 1989; 11: 238–242.

    PubMed  CAS  Google Scholar 

  21. Linder S, Weger A-R, Lindholm J, Jui H, Blåsjö M, Sundelin P, von Rosen A. Morphometric characteristics in adenocarcinoma of the pancreas and chronic pancreatitis.Scand J Gastroenterol 1994; 29: 764–768.

    Article  PubMed  CAS  Google Scholar 

  22. Eskelinen M, Lipponen P, Marin S, Haapasalo H, Mäkinen K, Ahtola H, Puittinen J, Nuutinen P, Alhava E. Prognostic factors in human pancreatic cancer, with special reference to quantitative histology.Scand J Gastroenterol 1991; 26: 483–490.

    Article  PubMed  CAS  Google Scholar 

  23. Klöppel G, Lingenthal G, von Bülow M, Kern HF. Histological and fine structural features of pancreatic ductal adenocarcinomas in relation to growth and prognosis: studies in xenografted tumors and clinico-histopathological correlation in a series of 75 cases.Histopathology 1985; 9: 841–856.

    Article  PubMed  Google Scholar 

  24. Atkin NB, Kay R. Prognostic significance of modal DNA value and other factors in malignant tumours, based on 1465 cases.Br J Cancer 1979; 40: 210–221.

    PubMed  CAS  Google Scholar 

  25. Eskelinen M, Lipponen P, Collan Y, Marin S, Alhava S, Nordling S. Relationship between DNA ploidy and survival in patients with exocrine pancreatic cancer.Pancreas 1991; 6: 90–95.

    Article  PubMed  CAS  Google Scholar 

  26. Wiechel K-L. Perkutane transhepatische Cholangiographie, inDie Erkrankungen der Gallenwege und des Pancreas. Band I. Hess W, Rohner A, Cirenei A, Akovbiantz A, eds. Piccin, Padua 1986, pp. 831–859.

    Google Scholar 

  27. Klöppel G. Pancreatic non-endocrine tumors, inPancreatic Pathology. Klöppel G, Heintz PU, eds. Churchill Livingstone, Edinburgh 1984, pp. 79–113.

    Google Scholar 

  28. Lindholm J, van Dienst PJ, Haffner D, Mikuz G, Weger A-R. A morphometric filter improves the diagnostic value of morphometric analyses of frozen histopathological sections from mammary tumors.Anal Cell Pathol 1992; 4: 443–449.

    PubMed  CAS  Google Scholar 

  29. Auer G, Askensten UG, Ahrens O. Cytophotometry.Hum Pathol 1989; 20: 518–527.

    Article  PubMed  CAS  Google Scholar 

  30. Askensten UG, von Rosen A, Nilsson RS, Auer GU. Intratumoral variations in DNA distribution patterns in mammary adenocarcinomas.Cytometry 1989; 10: 326–333.

    Article  PubMed  CAS  Google Scholar 

  31. Falkmer UG, Hagmar T, Auer GU. Efficacy of combined image and flow cytometric DNA assessments in human breast cancer. A methodologic study based on a routine histopathologic material of 2024 excised tumor specimens.Anal Cell Pathol 1989; 2: 297–312.

    Google Scholar 

  32. Lipponen P, Eskelinen M, Collan Y. Nuclear morphometry in human pancreatic adenocarcinoma; relation to histological grade, clinical stage, and survival.Ital J Gastroenterol 1990; 22: 124–128.

    PubMed  CAS  Google Scholar 

  33. Baisch H, Klöppel G, Reinke B. DNA ploidy and cell-cycle analysis in pancreatic and ampullary carcinoma: flow cytometric study of formalin-fixed paraffin-embedded tissue.Virchows Arch A Pathol Anat Histopathol 1990; 417: 145–150.

    Article  PubMed  CAS  Google Scholar 

  34. Böttger TC, Störkel S, Wellek S, Stöckle M, Junginger T. Factors influencing survival after resection of pancreatic cancer. A DNA analysis and a histomorphologic study.Cancer 1994; 73: 63–73.

    Article  PubMed  Google Scholar 

  35. Bose KK, Allison DC, Hruban RH, Piatantadosi S, Zahurak M, Dooley WC, Lin P, Cameron JL. A comparison of flow cytometric and absorption cytometric DNA values as prognostic indicators for pancreatic carcinoma.Cancer 1993; 71: 691–700.

    Article  PubMed  CAS  Google Scholar 

  36. Suto T, Sasaki K, Sugai T, Kanno S, Saito K. Heterogeneity in the nuclear DNA content of cells in carcinomas of the biliary tract and pancreas.Cancer 1993; 72: 2920–2928.

    Article  PubMed  CAS  Google Scholar 

  37. Weger AR, Glaser KS, Schwab G, Oefner D, Bodner E, Auer GU, Mikuz G. Quantitative nuclear DNA content in fine needle aspirates of pancreatic cancer.Gut 1991; 32: 325–328.

    Article  PubMed  CAS  Google Scholar 

  38. Linder S, Falkmer U, Hagmar T, Blåsjö M, Sundelin P, von Rosen A. Prognostic significance of DNA ploidy in pancreatic carcinoma.Pancreas 1994; 9: 764–772.

    Article  PubMed  CAS  Google Scholar 

  39. Auer GU, Caspersson TO, Wallgren AS. DNA content and survival in mammary carcinoma.Anal Quant Cytol 1980; 2: 161–165.

    PubMed  CAS  Google Scholar 

  40. Alanen KA, Joensuu H, Klemi PJ, Nevalainen TJ. Clinical significance of nuclear DNA content in pancreatic carcinoma.J Pathol 1990; 160: 313–320.

    Article  PubMed  CAS  Google Scholar 

  41. Azavedo E, Tribukait B, Konaka C, Auer G. Reproducibility of the cellular DNA-distribution patterns in multiple fine needle aspirates from human malignant tumors.APMIS 1982; 90: 79–83.

    CAS  Google Scholar 

  42. Weger A-R, Mikuz G, Askensten U, Auer GU, Schwab G, Glaser KS. Methodological aspects of DNA image cytometry in formalin-fixed paraffin-embedded material from pancreatic adenocarcinoma.Pathol Res Pract 1989; 185: 752–754.

    PubMed  CAS  Google Scholar 

  43. Porschen R, Remy U, Bevers G, Schauseil S, Hengels K-J, Borchard F. Prognostic significance of DNA ploidy in adenocarcinoma of the pancreas. A flow cytometric study of paraffin-embedded specimens.Cancer 1993; 71: 3846–3850.

    Article  PubMed  CAS  Google Scholar 

  44. Nitecki SS, Sarr MG, Colby TV, van Heerden JA. Long-term survival after resection for ductal adenocarcinoma of the pancreas. Is it really improving?Ann Surg 1995; 221: 59–66.

    Article  PubMed  CAS  Google Scholar 

  45. van der Putten HWHM, Baak JPA, Koenders TJM, Kurver PHJ, Stolk HG, Stolte LMA. Prognostic value of quantitative pathologic features and DNA content in individual patients with stage I endometrial adenocarcinoma.Cancer 1989; 63: 1378–1387.

    Article  PubMed  Google Scholar 

  46. Sorbe B, Risberg B, Thornthwaite J. Nuclear morphometry and DNA flow cytometry as prognostic methods for endometrial carcinoma.Int J Gynecol Cancer 1994; 4: 94–100.

    Article  PubMed  Google Scholar 

  47. Blomjous ECM, Schipper NW, Baak JPA, Vos W, de Voogt HJ, Meijer CJLM. The value of morphometry and DNA flow cytometry in addition to classic prognosticators in superficial urinary bladder carcinoma.Am J Clin Pathol 1989; 91: 243–248.

    PubMed  CAS  Google Scholar 

  48. Uyterlinde AM, Baak JPA, Schipper NW, Peterse H, Matze E, Meijer CJL. Further evaluation of the prognostic value of morphometric and flow cytometric parameters in breast-cancer patients with long follow-up.Int J Cancer 1990; 45: 1–7.

    Article  PubMed  CAS  Google Scholar 

  49. Warshaw AL. Implications of peritoneal cytology for staging of early pancreatic cancer.Am J Surg 1991; 161: 26–30.

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Surgery, Stockholm Söder Hospital, S-118 83, Stockholm, Sweden

    Stefan Linder

  2. Department of Pathology, Stockholm Söder Hospital, S-118 83, Stockholm, Sweden

    Margareta Blåsjö & Pär Sundelin

  3. Department of Pathology, Karolinska Hospital, Stockholm

    Ursula Falkmer

  4. Department of Surgery, Karolinska Hospital, Stockholm

    Anette von Rosen

  5. Department of Pathology, Danderyd Hospital, Danderyd, Sweden

    Johan Lindholm

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  1. Stefan Linder
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  4. Margareta Blåsjö
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  5. Pär Sundelin
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  6. Anette von Rosen
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Linder, S., Lindholm, J., Falkmer, U. et al. Combined use of nuclear morphometry and DNA ploidy as prognostic indicators in nonresectable adenocarcinoma of the pancreas. International Journal of Pancreatology 18, 241–248 (1995). https://doi.org/10.1007/BF02784948

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  • DOI: https://doi.org/10.1007/BF02784948

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