Annals of Oncology 5 (SuppL 3): S73-S74, 1994. O 1994 Kluwer Academic Publishers. Printed in the Netherlands.
Symposium article Surgery of pancreatic cancer J. Jeekel Department of Surgery, University Hospital Dijkzigt, Rotterdam, The Netherlands
The only treatment of pancreatic cancer which gives the patient a chance for cure is a surgical resection. There appears to be a wide variation in indications for treatment of pancreatic cancer. Some consider a size of the tumour of more than 2 cm a contra-indication for further treatment, others vascular abnormalities on angjogram or location of the tumour. Of course the main objective in the treatment of patients with pancreatic cancer is to prolong survival or obtain cure. One should adhere strictly to adequate prognostic parameters when defining the indication for treatment The problem is that there are not many significant prognostic parameters. This confusion, together with the high post operative mortality and morbidity, withholds many physicians from admitting the patients to the surgeon.
Indication for surgery
Tumour size is not a good prognostic sign in pancreatic cancer. Although it has been described that survival is shorter in case of a larger tumour size , there are other reports that indicate that there is a tendency for longer survival of patients with larger tumour [6, 7]. The problem is that exact tumour size is difficult to establish. The tumour visualised on CT-scan or ultrasound may be partly composed of infiltrative inflammatory cells. Furthermore it may be very difficult to establish preoperatively the exact nature of the tumour which may be a benign tumour instead of a malignant tumour or a cyste adenocarcinoma which may grow to a large size but still has a good prognosis after resection. Pancreatic tumours may grow to a large size without developing metastases. Survival in these patients is not
Key words: pancreatic cancer, surgery
significantly different from patients who undergo a so called curative resection if treatment is given with radiotherapy and 5-FU. It appears that such treatment with radiotherapy and 5-FU for locally unresectable pancreatic cancer without distant metastases may prolong median survival from 9 to 12 months [1-3] which is comparable to the median survival after curative resection. Survival of more than 5 years has been described in these patients [2, 3]. Apparently such locally invasive tumours react well to radiotherapy and 5-FU treatment. A few surgeons have performed a secondlook operation to study the effect of radiotherapy and 5-FU treatment and found in some cases such a dramatic effect that a Whipple's resection appeared to be possible after all, leading to long term survival [2, 4]. Thus treatment of large unresectable tumours may give similar results as surgical resection of resectable smaller pancreatic cancers. Therefore there is no contra-indication for treatment of pancreatic cancer as far as size is concerned. Lymph node metastases may be of prognostic value but are very difficult to establish preoperatively. Mostly only a suggestive evidence for lymph node metastases exists on CT scan. Large lymph nodes, for example in the hepato duodenal ligament, may be of benign nature. Distant metastases are a very bad prognostic sign in pancreatic cancer. Treatment is not indicated in these patients unless in a study design. Altogether there is only a clear cut contra-indication for further consideration of treatment when distant metastases are demonstrated in pancreatic cancer. Further information on the nature of the tumour, the exact size of the tumour, the resectability of the tumour and presence of lymph node metastases can only be obtained with certainty during a laparotomy. A laparotomy should only be performed if treatment
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Pancreatic cancer which has an increasing incidence in the western countries is associated with an especially poor prognosis. This is mainly due to the low proportion of early and radically resectable stages, when diagnosed. Patients with irresectable disease have a median survival time of 3-4 months and their prognosis is not essentially improved by chemo-
therapy and/or radiotherapy. Nevertheless, surgical resection should be performed if possible, although the 5-year survival rates are in the range of 5-15%, only. Apart from other locations, periampullar pancreatic cancer has a markedly better prognosis with 5-year survival rates of 25%-35% after curative resection.
74 is considered. As indicated above treatment is also considered in case of locally advanced unresectable pancreatic cancer without distant metastases. Therefore a laparotomy is indicated in all cases of pancreatic cancer where distant metastases have not been demonstrated (any T, NO-1A). If the tumour appears resectable during laparotomy, a Whipple's resection is performed unless distant metastases are demonstrated. If the patient has an unresectable tumour but is free of metastases, radiotherapy and 5-FU treatment is indicated. Surgical technique
Non-surgical treatment A Whipple's resection is in many instances not radical and may be considered as a lumpectomy like in breast cancer. Apparently tumour cells are often left behind, considering the very high incidence of local recurrence in this disease. Adjuvant treatment might therefore be of value after so-called curative resection. One randomized prospective study has been described . In this study radiotherapy and 5-FU treatment was given
References 1. Moertel CG, Frytak S, Hahn RG et al. Therapy of locally unresectable pancreatic carcinoma Cancer 1981; 48:1705-10. 2. Jeekel J, Treumiet-Donker AD. Treatment perspectives in locally advanced unresectable pancreas cancer. Br J Surg 1991; 11:1331-4. 3. Treurniet-Donker AD, van Mierlo MJM, van Putten WLJ. Localized unresectable pancreatic cancer. Int J Radiation Oncology 1990; 18: 59-62. 4. Pilepich MV, Miller HH. Preoperative irradiation in carcinoma of the pancreas. Cancer 1980; 46:1945-9. 5. Tsuchiya R, Noda T, Harada N et al. Collective review of small carcinomas of the pancreas. Ann Surg 1986; 203(1): 77-81. 6. Van Heerden JA, Mcllrath DC, Ilstrup D et al. Total pancreatectomy for ductal adenocarcinoma of the pancreas: An update. World J Surg 1988; 12: 658-62. 7. Klinkenbijl JHG, Jeekel J, Schmitz PIM ct al. Carcinoma of the pancreas and periampullary region, palliation or cure? A review of 310 patients. Accepted for publication in the Br J Surg. 8. Klinkenbijl JHG, Van der Schelling GP, Hop WCJ et al. The advantages of Pylorus-preserving pancreatodeuodenectomy in malignant disease of the pancreas and periampullary region. Ann of Surg 1992:216(2): 142-5. 9. Whipple AO, Parsons W, Mullins CR. Treatment of carcinoma of the ampulla of Vater. Ann Surg 1935; 102: 763-79. 10. Watson K. Carcinoma of the ampulla of Vater, successful radical resection. BrJ Surg 1944; 31: 368-73. 11. Kaiser MH, Ellenberg SS. Pancreatic Cancer. Adjuvant Combined and Chemotherapy following Curative Resection. Arch Surg 1985; 120: 899-903. Correspondence to: Prof. Dr. J. Jeekel, MJ). Department of Surgery University Hospital Dijkzigt 40 Dr. Molewaterplein NL-3015 GD Rotterdam The Netherlands
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Whipple et al. described in 1935 the first resection of the head of the pancreas for malignant disease. It still is a treatment of choice for pancreatic cancer in the head of the pancreas and periampullary region . In 1944 Watson described for the first time the pylorus preserving pancreatoduodenectomy . We have studied pylorus preserving pancreatoduodenectomy versus Whipple's resection and found that there was a clear advantage of the pylorus preserving procedure . Hospital stay appeared to be significantly shorter after pylorus preserving resection. Operation time was significantly shorter with less blood loss and during follow-up there appeared to be a better weight gain in the pylorus preserving group. There was no difference in ultimate survival. We have embarked a prospective randomised study to confirm these data. The Whipple's resection is a hazardous procedure. One should especially avoid leakage of the pancreatico jejunostomy. In our hands a single layer running PDS suture is used for this anastomosis without a stenL It is of great importance to diminish the chance of mortality and morbidity during a Whipple's resection. An experienced surgeon should perform the operation. Post-operative complications should be treated well. When the leakage of the pancreatico jejunostomy occurs, the anastomosis should be disconnected, the jejunum closed at this side and the pancreatic remnant should be treated by injection of the duct with for example ethibloc. One should avoid the construction of a new anastomosis.
after Whipple's resection for pancreatic cancer. A 2-year survival appeared to be significantly higher in the patients receiving adjuvant treatment compared to the untreated control group. However the accrual time took nearly 10 years and the number of patients was small. We therefore have started a randomized prospective study in 1990 to study the adjuvant treatment with radiotherapy and 5-FU. Adjuvant treatment with hormonal treatment has been studied but so far did not give conclusive data. Hormonal treatment should be given in case of neuroendocrine tumours. It is very well possible that some long term survivors had a neuro-endocrine tumour in stead of an adenocarcinoma of the pancreas. The pathologist should look for evidence of neuro endocrine tumours. Altogether there is no reason for nihilism in pancreatic cancer. A 5-year survival of between 10% and 20% can be obtained. There is an indication for treatment in all patients without distant metastases.