Annals of Surgical Oncology

, Volume 14, Issue 12, pp 3443–3452 | Cite as

Incidence of Postoperative Pancreatic Fistula and Hyperamylasemia after Cytoreductive surgery and Hyperthermic Intraperitoneal Chemotherapy

  • Shigeki Kusamura
  • Dario Baratti
  • Adelmo Antonucci
  • Rami Younan
  • Barbara Laterza
  • Grazia Daniela Oliva
  • Cecilia Gavazzi
  • Marcello Deraco
Gastrointestinal Oncology Original Papers



The purpose of this study was to analyze the postoperative pancreatic morbidity of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in the treatment of peritoneal surface malignancies (PSM).

Patients and methods

Two hundred and sixty five patients (87M/178F) with PSM underwent 270 consecutive procedures. The mean age was 52 years (range: 22–79 years). CRS was performed using peritonectomy procedures. HIPEC through the closed abdomen technique was conducted using cisplatin (CDDP 25mg/m2/L of perfusate)+mitomycin C (MMC 3.3 mg/m2/L of perfusate) or CDDP (43mg/L of perfusate)+doxorubicin (Dx 15.25 mg/L of perfusate), at 42.5°C. Diagnosis and classification of postoperative pancreatic fistula (POPF) were performed according to the international study group on pancreatic fistula criteria. Serum amylase alterations were graded according to the National Cancer Institute (NCI) common terminology criteria for adverse events (CTCAE) v3.


POPF was observed in 13 (4.8%) cases. Three cases were classified as major (grade C). Two cases presented postoperative pancreatitis. G3-4 alteration of amylase was observed in 12.3% of the cases. Performing splenectomy and CDDP dosage for HIPEC >240mg were proven to be independent risk factors for both G3-4 hyperamylasemia and POPF.


CRS+HIPEC presented an acceptable rate of pancreatic morbidity which did not contribute to the mortality related to the procedure. Most of the POPF were mild and/or easily controlled by conservative measures. Although not specific a normal amylasemia could be a useful marker of pancreatic integrity after CRS+HIPEC.


Peritonectomy hyperthermic intraperitoneal chemotherapy Toxicity 



Supported in part by grants from the Associazione Italiana Ricerca sul Cancro (AIRC).


  1. 1.
    Deraco M, Baratti D, Inglese MG, Allaria B, Andreola S, Gavazzi C, Kusamura S. Peritonectomy and intraperitoneal hyperthermic perfusion (IPHP): a strategy that has confirmed its efficacy in patients with pseudomyxoma peritonei. Ann Surg Oncol 2004; 11(4):393–8PubMedCrossRefGoogle Scholar
  2. 2.
    Deraco M, Casali P, Inglese MG, Baratti D, Pennacchioli E, Bertulli R, Kusamura S. Peritoneal mesothelioma treated by induction chemotherapy, cytoreductive surgery, and intraperitoneal hyperthermic perfusion. J Surg Oncol 2003; 83:147–53PubMedCrossRefGoogle Scholar
  3. 3.
    Ryu KS, Kim JH, Ko HS, Kim JW, Ahn WS, Park YG, Kim SJ, Lee JM. Effects of intraperitoneal hyperthermic chemotherapy in ovarian cancer. Gynecol Oncol 2004; 94:325–32PubMedCrossRefGoogle Scholar
  4. 4.
    Glehen O, Kwiatkowski F, Sugarbaker PH, Elias D, Levine EA, De Simone M, Barone R, Yonemura Y, Cavaliere F, Quenet F, Gutman M, Tentes AA, Lorimier G, Bernard JL, Bereder JM, Porcheron J, Gomez-Portilla A, Shen P, Deraco M, Rat P. Cytoreductive surgery combined with perioperative intraperitoneal chemotherapy for the management of peritoneal carcinomatosis from colorectal cancer: a multi-institutional study. J Clin Oncol 2004; 22:3284–92PubMedCrossRefGoogle Scholar
  5. 5.
    Verwaal VJ, van Ruth S, de Bree E, van Sloothen GW, van Tinteren H, Boot H, Zoetmulder FA. Randomized trial of cytoreduction and hyperthermic intraperitoneal chemotherapy versus systemic chemotherapy and palliative surgery in patients with peritoneal carcinomatosis of colorectal cancer. J Clin Oncol 2003; 21:3737–43PubMedCrossRefGoogle Scholar
  6. 6.
    Jacquet P, Stephens AD, Averbach AM, Chang D, Ettinghausen SE, Dalton RR, Steves MA, Sugarbaker PH. Analysis of morbidity and mortality in 60 patients with peritoneal. carcinomatosis treated by cytoreductive surgery and heated intraoperative intraperitoneal chemotherapy. Cancer 1996; 77:2622–9PubMedCrossRefGoogle Scholar
  7. 7.
    Stephens AD, Alderman R, Chang D, Edwards GD, Esquivel J, Sebbag G, Steves MA, Sugarbaker PH. Morbidity and mortality analysis of 200 treatments with cytoreductive surgery and hyperthermic intraoperative intraperitoneal chemotherapy using the coliseum technique. Ann Surg Oncol 1999; 6:790–6PubMedCrossRefGoogle Scholar
  8. 8.
    Glehen O, Osinsky D, Cotte E, Kwiatkowski F, Freyer G, Isaac S, Trillet-Lenoir V, Sayag-Beaujard AC, Francois Y, Vignal J, Gilly FN. Intraperitoneal chemohyperthermia using a closed abdominal procedure and cytoreductive surgery for the treatment of peritoneal carcinomatosis: morbidity and mortality analysis of 216 consecutive procedures. Ann Surg Oncol 2003; 10:863–9PubMedCrossRefGoogle Scholar
  9. 9.
    Verwaal VJ, van Tinteren H, Ruth SV, Zoetmulder FA. Toxicity of cytoreductive surgery and hyperthermic intra-peritoneal chemotherapy. J Surg Oncol 2004; 85:61–7PubMedCrossRefGoogle Scholar
  10. 10.
    Shen P, Hawksworth J, Lovato J, Loggie BW, Geisinger KR, Fleming RA, Levine EA. Cytoreductive surgery and intraperitoneal hyperthermic chemotherapy with mitomycin C for peritoneal carcinomatosis from nonappendiceal colorectal carcinoma. Ann Surg Oncol 2004; 11:178–86PubMedCrossRefGoogle Scholar
  11. 11.
    Kusamura S, Younan R, Baratti D, Costanzo P, Favaro M, Gavazzi C, Deraco M. Cytoreductive surgery followed by intraperitoneal hyperthermic perfusion: analysis of morbidity and mortality in 209 peritoneal surface malignancies treated with closed abdomen technique. Cancer 2006; 106(5):1144–53PubMedCrossRefGoogle Scholar
  12. 12.
    Tansung T, Sugarbaker PH. Management of pancreatitis due to pancreatic injury in cytoreductive surgery. Reg Cancer Treat 1995; 8:180–4Google Scholar
  13. 13.
    Sugarbaker PH. Peritonectomy procedures. Ann Surg 1995; 221:29–42PubMedCrossRefGoogle Scholar
  14. 14.
    Sugarbaker PH. Laser-mode electrosurgery. Cancer Treat Res 1996; 82:375–85PubMedGoogle Scholar
  15. 15.
    Younan R, Kusamura S, Baratti D, Oliva GD, Costanzo P, Favaro M, Gavazzi C, Deraco M. Bowel complications in 203 cases of peritoneal surface malignancies treated with peritonectomy and closed-technique intraperitoneal hyperthermic perfusion. Ann Surg Oncol 2005; 12(11):910–8PubMedCrossRefGoogle Scholar
  16. 16.
    Jacquet P, Sugarbaker PH. Current methodologies for clinical assessment of patients with peritoneal carcinomatosis. J Exp Clin Cancer Res 1996; 15:49–58Google Scholar
  17. 17.
    Fujimoto S, Takahashi M, Kobayashi K, Kure M, Masaoka H, Ohkubo H, Isaka S, Shimazaki J. Combined treatment of pelvic exenterative surgery and intra-operative pelvic hyperthermochemotherapy for locally advanced rectosigmoid cancer: report of a case. Surg Today 1993; 23:1094–8PubMedCrossRefGoogle Scholar
  18. 18.
    Rossi CR, Foletto M, Mocellin S, Pilati P, De SM, Deraco M, Cavaliere F, Palatini P, Guasti F, Scalerta R, Lise M. Hyperthermic intraoperative intraperitoneal chemotherapy with cisplatin and doxorubicin in patients who undergo cytoreductive surgery for peritoneal carcinomatosis and sarcomatosis: phase I study. Cancer 2002; 94:492–9PubMedCrossRefGoogle Scholar
  19. 19.
    Bassi C, Dervenis C, Butturini G, Fingerhut A, Yeo C, Izbicki J, Neoptolemos J, Sarr M, Traverso W, Buchler M. International Study Group on Pancreatic Fistula Definition. Postoperative pancreatic fistula: an international study group (ISGPF) definition. Surgery 2005; 138(1):8–13PubMedCrossRefGoogle Scholar
  20. 20.
    Swaroop VS, Chari ST, Clain JE. Severe acute pancreatitis. JAMA 2004; 291(23):2865–8PubMedCrossRefGoogle Scholar
  21. 21.
    Dawson-Saunders B, Trapp RG. Basic and Clinical Biostatistics, Second Edition. Norwalk, Connecticut. Appleton & LangeGoogle Scholar
  22. 22.
  23. 23.
    Chand B, Walsh RM, Ponsky J, Brody F. Pancreatic complications following laparoscopic splenectomy. Surg Endosc 2001; 15(11):1273–6PubMedCrossRefGoogle Scholar
  24. 24.
    Delaitre B, Champault G, Barrat C, Gossot D, Bresler L, Meyer C, Collet D, Samama G. Laparoscopic splenectomy for hematologic diseases. Study of 275 cases. French Society of Laparoscopic Surgery. Ann Chir 2000; 125(6):522–9. FrenchPubMedCrossRefGoogle Scholar
  25. 25.
    Hendricks T, Martens MF, Huyben CM, Wobbes T. Inhibition of basal and TGF beta-induced fibroblast collagen synthesis by antineoplastic agents. Implications for wound healing. Br J Cancer 1993; 67(3):545–50PubMedGoogle Scholar
  26. 26.
    Rattner DW, Gu ZY, Vlahakes GJ, Warshaw AL. Hyperamylasemia after cardiac surgery. Incidence, significance, and management. Ann Surg 1989; 209(3):279–83PubMedCrossRefGoogle Scholar
  27. 27.
    Hashimoto N, Haji S, Nomura H, Ohyanagi H. Hyperamylasemia after hepatic resection. Hepatogastroenterology 2003; 50(53):1472–3PubMedGoogle Scholar
  28. 28.
    Baniel J, Leibovitch I, Foster RS, Rowland RG, Bihrle R, Donohue JP. Hyperamylasemia after post-chemotherapy retroperitoneal lymph node dissection for testis cancer. J Urol 1995; 154(4):1373–5PubMedCrossRefGoogle Scholar
  29. 29.
    Korenaga D, Watanabe A, Baba H, Saito A, Maehara Y, Sugimachi K. Hyperamylasemia associated with lymphadenectomy in patients surgically treated for gastric cancer. Eur J Surg Oncol 1992; 18(2):135–41PubMedGoogle Scholar
  30. 30.
    Leclerc P, Forest JC. Variations in amylase isoenzymes and lipase during acute pancreatitis, and in other disorders causing hyperamylasemia. Clin Chem 1983; 29(6):1020–3PubMedGoogle Scholar
  31. 31.
    Baronofsky ID, Wwalton W, Noble JF. Occult injury to the pancreas following splenectomy. Surgery 1951; 29(6):852–7PubMedGoogle Scholar
  32. 32.
    Paajanen H, Nuutinen P, Harmoinen A, Poyhonen M, Pitkanen O, Nordback I, Gronroos J, Nevalainen TJ. Hyperamylasemia after cardiopulmonary bypass: pancreatic cellular injury or impaired renal excretion of amylase? Surgery 1998; 123(5):504–10PubMedCrossRefGoogle Scholar
  33. 33.
    Li-Ling J, Irving M. Somatostatin and octreotide in the prevention of postoperative pancreatic complications and the treatment of enterocutaneous pancreatic fistulas: a systematic review of randomized controlled trials. Br J Surg 2001; 88(2):190–9PubMedCrossRefGoogle Scholar
  34. 34.
    Balcom JH 4th, Keck T, Warshaw AL, Graeme-Cook F, Fernandez-del Castillo C. Prevention of pancreatic fistula with a new synthetic, absorbable sealant: evaluation in a dog model. J Am Coll Surg 2002; 195(4):490–6PubMedCrossRefGoogle Scholar

Copyright information

© Society of Surgical Oncology 2007

Authors and Affiliations

  • Shigeki Kusamura
    • 1
  • Dario Baratti
    • 1
  • Adelmo Antonucci
    • 1
  • Rami Younan
    • 3
  • Barbara Laterza
    • 1
  • Grazia Daniela Oliva
    • 1
  • Cecilia Gavazzi
    • 2
  • Marcello Deraco
    • 1
    • 4
  1. 1.Dept of SurgeryNational Cancer Institute of MilanMilanItaly
  2. 2.Nutritional Care UnitNational Cancer Institute of MilanMilanItaly
  3. 3.Dept of Surgery – Surgical Oncology UnitCHUM, University of Montreal Health CentreMontrealCanada
  4. 4.Istituto Nazionale Tumori MilanoMilanoItalia

Personalised recommendations