European Journal of Surgical Oncology 1999; 25: 132–137 (Neo)adjuvant treatment in pancreatic cancer— the need for future trials C. H. J. van Eijck*, K. H. Link†, M. E. E. van Rossen* and J. Jeekel* *Erasmus Medical Centre Rotterdam, The Netherlands and †Universita ¨tsklinikum Ulm, Germany Introduction rates (20–40%) of pancreatic tumours due to (local) retroperitoneal advancement, support the rationale for pre- operative neoadjuvant or post-operative adjuvant therapy Pancreatic cancer is one of the most fatal malignant diseases of today and ranks fifth in cancer incidence and mortality in operable pancreatic cancer patients. worldwide. 1,2 Patients with pancreatic cancer can be cured by surgery only when detected early, but most patients present with incurable disease. Resection by partial or total Neoadjuvant treatment pancreaticoduodenectomy is possible in no more than 8–25% of patients. 3,4 The success of surgical treatment is There are several arguments for pre-operative multimodality often limited due to locoregional recurrence or the therapy to improve the outcome of pancreatic cancer even development of distant metastases and peritoneal carcinosis. after intentional curative primary tumour resection. In vivo This local or systemic relapse is supposed to be caused by response evaluation of therapy could be an important cells that have already been seeded before or at the time of prognostic factor. Patients who develop liver metastasis or operation, and could not be detected with conventional peritonitis carcinomatosis within a short period of time after methods. 5–7 starting systemic therapy should not be operated initially. Several studies have been performed to diagnose pre- In cases of responding tumours, less surgical tumour cell operative seeding in the peritoneal cavity, and thus incurable dissemination is likely to occur and the possible influence disease, by lavaging the abdomen and performing a of post-surgical growth factors on these cells may be altered. cytological and immunohistochemical study of the lavage Another advantage of pre-operative systemic and/or fluids. 8–12 Warshaw et al. found malignant tumour cells in locoregional therapy in contrast to adjuvant therapy is the 30% of patients with early pancreatic cancer. 11 Positive improved ability to deliver planned treatment in randomized cytological results could be found more often in patients trials, as post-operative morbidity has no influence on the who had undergone percutaneous needle biopsy (75 vs. intake of patients. Most of these neoadjuvant studies, 19%). In a retrospective study, Makary et al. demonstrated however, require histopathological confirmation of that pancreatic cancer patients with positive cytology have pancreatic malignancy, which is not always possible. Due a dismal outcome even without macroscopic metastases. 13 to the risk of intraperitoneal tumour cell spillage after Immunocytological micrometastases were detected in 58% transperitoneal aspiration biopsies this procedure has been of 32 patients who underwent surgery for pancreatic cancer, abandoned in most centres. and were present not only in the peritoneal cavity but also The approach to treat all tumours before resection has already in the bone marrow. 14 The evaluation of radical been successfully applied in childhood tumours operations (R0 resection) showed that in 45% of the patients (hepatoblastoma, Wilms’ tumour), sarcomas, and breast tumour cells were present in the bone marrow and/or cancer, either to achieve better survival rates or allow more peritoneal cavity at the time of operation. Two-stage conservative and less mutilating surgery. The first studies polymerase chain reaction (PCR) and restriction fragment in pancreatic cancer patients were conducted with pre- length polymorphism analysis (RFLP) were used to detect operative radiotherapy, as suggested by Tepper. 16 Pilepich K-ras oncogene mutation at codon 12 in liver tissue and Miller used pre-operative radiotherapy of 45 Gy in 17 specimens, obtained from 17 pancreatic cancer patients after patients with initially unresectable locally advanced laparotomy. In 10 out of 13 patients without macroscopic pancreatic tumours. Six were considered resectable at hepatic metastasis, K-ras gene mutations in the liver were second-look laparotomy, two of them surviving 2.5 years detected. 15 after Whipple’s resection. Clear conversion from an The presence of micrometastasis, either in the peritoneal unresectable to a resectable lesion could be documented in cavity, liver or bone marrow, in addition to low resectability only one patient. 17 Ishikawa et al. 18 found, in a comparative case control study, that pre-operative irradiation Correspondence to: C. H. J. van Eijck, Dept of Surgery, Erasmus downstaged the tumour and decreased local recurrence rates University Hospital, Dr. Molewaterplein 40, 3015 GD Rotterdam, The Netherlands. and early death from local recurrence. However, resectability 0748–7983/99/020132+06 $12.00/0  1999 W.B. Saunders Company Limited