Indications for Surgical Treatment of Pancreatic Cancer J. JEEKEL Dept. of Surgery, University Hospital Dijkzigt, Rotterdam, The Netherlands
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Jeekel J. Indications for surgical treatment of pancreatic cancer. Scand J Gastroenterol 1992; Suppl 194:59-60. The best chance for cure of pancreatic cancer is surgical resection. This is also possible in case of adjacent organ involvement of, for example. duodenum, portal vein, or colon. Pancreatic tumours may develop to a large size without developing metastases. Irresectable tumours without distant metastases can successfully be treated with radiotherapy and 5-Ruorouracil and. in some cases, be resected during a second-look operation. Thus there is no contraindication for laparotomy in case of large size. Preoperatively estimated size of the tumour is not of prognostic value for resection. Altogether, laparotomy is contraindicated only in case of distant mestastases and high operative risk. Key words: Metastasis; pancreatic cancer; surgery; therapy Prof. J . Jeekel, M . D . , Dept. of Surgery, University Hospital Dijkzigt, 40 Dr. Molewarerplein, NL-3015 C D Rotterdam, The Netherlands
Many physicians, internists, and surgeons have a fatalistic approach towards pancreatic cancer disease. This nihilism is caused by the infaust prognosis of most patients with pancreatic cancer and by the operative risks of pancreaticoduodenectomy. Such an attitude, however, may wrongly exclude patients from treatment. The primary objective in pancreatic cancer is to offer the patients adequate treatment, which may be largely palliative. The primary problem is to obtain an accurate assessment of the stage of the disease without invasive surgical procedures. Ideally, it should be possible to identify patients with shortterm infaust prognosis and patients with resectable tumours and localized cancer. In this manner unnecessary treatment may be avoided without missing a chance for cure. Another major reason for withholding adequate treatment is the ignorance of certain treatment options and therefore a misunderstanding of indications for surgery. Some diagnostic findings are considered an important prognostic factor without clear clinical evidence, such as, for example, tumour size. TREATMENT OPTIONS For most solid cancers the best chance for cure is offered by surgical resection. Such resection is possible when the tumour invasion in surrounding tissue is limited and the operative risk is not too high. Owing to its anatomic position advanced pancreatic tumour may be unresectable in an early phase. In case of adjacent organs involvement, however, Whipple’s resection can often still be performed. Tumour ingrowth in duodenum, mesenteric vein, portal vein, mesentery of the transverse colon or colon does not necessarily preclude en-bloc resection of tumour and surrounding structures.
It appears that pancreatic tumours may grow to a large size without developing metastases. Such tumours seem to have a different biologic behaviour. This hypothesis is supported by the long-term survival that can be obtained in these patients. Several studies show that radiotherapy and 5-fluorouracil (5-FU) treatment of locally unresectable pancreatic cancer may prolong median survival time from 3-5 months to 9-12 months (1-3). Survival of more than 5 years has been obtained (2, 3). In a few studies the effect of combined treatment with radiotherapy and 5-FU has also been shown at second-look laparotomy (2, 4). In some cases the tumour size decreased significantly, enabling resection of the pancreas and duodenum. Thus there is place for treatment of both resectable and unresectable pancreatic tumours if there are no distant metastases. This has important implications for the indications for laparotomy when a pancreatic tumour is suspected. PROGNOSTIC FACTORS It is important to avoid surgery if there is a short-term infaust prognosis. This is the case when distant metastases are present. These patients have a median survival time of 3-4 months. Surgery should also be avoided if the operative risk is too high. Increased risk has been described in the older age group. Operative mortality is still high in many centres. Age and condition of the patient are important aspects. So far I have avoided a Whipple resection in patients older than 80 years, although the mortality rate in my series of patients older than 70 years was 0%. Many physicians take the size of the tumour as an important factor. It has indeed been observed that survival is
Scand J Gastroenterol Downloaded from informahealthcare.com by University of Toronto on 11/26/14 For personal use only.
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J . Jeekel
short in case of larger tumour size (5), but other reports do not support this point of view ( 6 1 1 ) . We and others even noted a tendency (11, 12) for longer survival rate after Whipple’s resection for larger tumours. This is in line with the above-described hypothesis that some large localized tumours may be of a different kind. Gudjonsson (13) described longer survival in patients with positive findings on ultrasound and computed tomography scan studies and physical examination. The estimated size of the tumour is often highly inaccurate. Furthermore, it is nearly impossible to differentiate with radiologic methods between pancreatic cancer and other tumours with a more benign character. A part of the tumour may in fact be infiltration of inflammatory cells, which may also simulate cancer infiltration in surrounding tissue, such as, for example, portal vein invasion. Tumours with a more benign character are cystadenocarcinoma, lymphoma, endocrine tumours, insulinoma, gastrinoma, carcinoid, sarcoidosis, and tuberculosis. Cystic tumours like papillary cystic neoplasm and mucinous cystadenomas may occur in young women. Needle-aspiration cytology may distinguish between pancreatic cancer and other tumours. Thus tumour size per se does not have a clear prognostic value. Large tumours without metastases may be of a less aggressive character. Ingrowth in surrounding tissue does not have to imply unresectability. There are no reports available on prospective studies of the prognostic value of invasion of portal vein. Recently, Ishikawa et al. (14) described a retrospective study in which portal vein invasion of more than 1.2cm appeared to be of prognostic value. Patients with bilateral narrowing of the portal vein and collateral veins did not survive for more than 1.5 years after resection. Our own experience indicates that tumour ingrowth may appear t o be of non-carcinomatous origin when the resected specimen is carefully investigated. This is in line with the 40% non-carcinomatous invasion found in colon cancer with adjacent organ involvement (15). So far there are no data available to establish any prognostic value of portal invasion or presence of collateral veins. The presence of lymph node metastases is of prognostic value according to some authors, although others do not confirm this. This is of limited value as a preoperative diagnostic tool because accurate diagnosis is only possible after surgical resection.
INDICATIONS FOR LAPAROTOMY There is an indication for laparotomy if treatment is considered. Surgical treatment for pancreatic cancer is not indicated if distant metastases are present ( N l b , M l ) . In all other cases (any T NO, l a ) a laparotomy should be performed to establish resectability. If the tumour is not resectable and distant metastases are not present, radiotherapy and 5-FUtreatment is given in the unresectable cases. The exact nature of the tumour should be established t o give adequate treatment. The overall cure rate in case of pancreatic tumours may be improved if all treatment options are known to the physician.
REFERENCES 1. Moertel CG, Frytak S , Hahn RG, et al. Therapy of locally unresectable pancreatic carcinoma. Cancer 1981;48:1705-10. 2. Jeekel J, Treurniet-Donker AD. Treatment perspectives in locally advanced unresectable pancreas cancer. Br J Surg 199 1 ;1 1:1331 4 . 3. Treurniet-Donker AD, vanMierlo MJM, vanputten WLJ.
Localized unresectable pancreatic cancer. Int J Radiat Oncol 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;203:77-81. 6. Mannell A, Weiland LH, van Heerden JA, et al. Actors influencing survival after resection for ductal adenocarcinoma of the pancreas. Ann Surg 1986;203:403-7. 7. Nagakawa T, Kanoshi I, Ueno K, et al. Surgical treatment of pancreatic cancer. Int J Pancreatol 1991;9:135-43. 8. Andren-Sandberg A. Factors influencing survival after total
pancreatectomy in patients with pancreatic cancer. Ann Surg 1991;214:605-10. 9. Sato T, Saitoh Y, Noto N, et al. Follow-up studies of radical resection for pancreaticoduodenal cancer. Ann Surg 1977; 186:581-8. 10. Williams J, Cubilla A, Maclean B, et al. Twenty-two year
experience with periampullary carcinoma at Memorial SloanKettering Cancer Center. Am J Surg 1979;138:662-5. 11. Van Heerden JA, McIlrath DC, Ilstrup D, et al. Total pancreatectomy for ductal adenocarcinoma of the pancreas: an update. World J Surg 1988;12:658-62. 12. Klinkenbijl J. Carcinoma of the pancreas and periampullary region, palliation or cure? A review of 310 patients. Br J Surg. 13. Gudjonsson B. Cancer of the pancreas. Cancer 1987;60:2284303. 14. Ishikawa 0, Ohigashi H, Imaoka S , et al. Preoperative indi-
cations for extended pancreatectomy for locally advanced pancreas involving the portal vein. Ann Surg 1992;215:231-6. 15. Kroneman H, Castelein A, Jeekel J. En bloc resection of colon adherent to other organs; an efficacious treatment? Dis Colon Rectum 1991;34:780-3.
Scand J Gastroenterol Downloaded from informahealthcare.com by University of Toronto on 11/26/14 For personal use only.
Jeekel J. Indications for surgical treatment of pancreatic cancer. Scand J Gastroenterol 1992; Suppl 194:59-60. The best chance for cure of pancreatic cancer is surgical resection. This is also possible in case of adjacent organ involvement of, for example. duodenum, portal vein, or colon. Pancreatic tumours may develop to a large size without developing metastases. Irresectable tumours without distant metastases can successfully be treated with radiotherapy and 5-Ruorouracil and. in some cases, be resected during a second-look operation. Thus there is no contraindication for laparotomy in case of large size. Preoperatively estimated size of the tumour is not of prognostic value for resection. Altogether, laparotomy is contraindicated only in case of distant mestastases and high operative risk. Key words: Metastasis; pancreatic cancer; surgery; therapy Prof. J . Jeekel, M . D . , Dept. of Surgery, University Hospital Dijkzigt, 40 Dr. Molewarerplein, NL-3015 C D Rotterdam, The Netherlands
Many physicians, internists, and surgeons have a fatalistic approach towards pancreatic cancer disease. This nihilism is caused by the infaust prognosis of most patients with pancreatic cancer and by the operative risks of pancreaticoduodenectomy. Such an attitude, however, may wrongly exclude patients from treatment. The primary objective in pancreatic cancer is to offer the patients adequate treatment, which may be largely palliative. The primary problem is to obtain an accurate assessment of the stage of the disease without invasive surgical procedures. Ideally, it should be possible to identify patients with shortterm infaust prognosis and patients with resectable tumours and localized cancer. In this manner unnecessary treatment may be avoided without missing a chance for cure. Another major reason for withholding adequate treatment is the ignorance of certain treatment options and therefore a misunderstanding of indications for surgery. Some diagnostic findings are considered an important prognostic factor without clear clinical evidence, such as, for example, tumour size. TREATMENT OPTIONS For most solid cancers the best chance for cure is offered by surgical resection. Such resection is possible when the tumour invasion in surrounding tissue is limited and the operative risk is not too high. Owing to its anatomic position advanced pancreatic tumour may be unresectable in an early phase. In case of adjacent organs involvement, however, Whipple’s resection can often still be performed. Tumour ingrowth in duodenum, mesenteric vein, portal vein, mesentery of the transverse colon or colon does not necessarily preclude en-bloc resection of tumour and surrounding structures.
It appears that pancreatic tumours may grow to a large size without developing metastases. Such tumours seem to have a different biologic behaviour. This hypothesis is supported by the long-term survival that can be obtained in these patients. Several studies show that radiotherapy and 5-fluorouracil (5-FU) treatment of locally unresectable pancreatic cancer may prolong median survival time from 3-5 months to 9-12 months (1-3). Survival of more than 5 years has been obtained (2, 3). In a few studies the effect of combined treatment with radiotherapy and 5-FU has also been shown at second-look laparotomy (2, 4). In some cases the tumour size decreased significantly, enabling resection of the pancreas and duodenum. Thus there is place for treatment of both resectable and unresectable pancreatic tumours if there are no distant metastases. This has important implications for the indications for laparotomy when a pancreatic tumour is suspected. PROGNOSTIC FACTORS It is important to avoid surgery if there is a short-term infaust prognosis. This is the case when distant metastases are present. These patients have a median survival time of 3-4 months. Surgery should also be avoided if the operative risk is too high. Increased risk has been described in the older age group. Operative mortality is still high in many centres. Age and condition of the patient are important aspects. So far I have avoided a Whipple resection in patients older than 80 years, although the mortality rate in my series of patients older than 70 years was 0%. Many physicians take the size of the tumour as an important factor. It has indeed been observed that survival is
Scand J Gastroenterol Downloaded from informahealthcare.com by University of Toronto on 11/26/14 For personal use only.
60
J . Jeekel
short in case of larger tumour size (5), but other reports do not support this point of view ( 6 1 1 ) . We and others even noted a tendency (11, 12) for longer survival rate after Whipple’s resection for larger tumours. This is in line with the above-described hypothesis that some large localized tumours may be of a different kind. Gudjonsson (13) described longer survival in patients with positive findings on ultrasound and computed tomography scan studies and physical examination. The estimated size of the tumour is often highly inaccurate. Furthermore, it is nearly impossible to differentiate with radiologic methods between pancreatic cancer and other tumours with a more benign character. A part of the tumour may in fact be infiltration of inflammatory cells, which may also simulate cancer infiltration in surrounding tissue, such as, for example, portal vein invasion. Tumours with a more benign character are cystadenocarcinoma, lymphoma, endocrine tumours, insulinoma, gastrinoma, carcinoid, sarcoidosis, and tuberculosis. Cystic tumours like papillary cystic neoplasm and mucinous cystadenomas may occur in young women. Needle-aspiration cytology may distinguish between pancreatic cancer and other tumours. Thus tumour size per se does not have a clear prognostic value. Large tumours without metastases may be of a less aggressive character. Ingrowth in surrounding tissue does not have to imply unresectability. There are no reports available on prospective studies of the prognostic value of invasion of portal vein. Recently, Ishikawa et al. (14) described a retrospective study in which portal vein invasion of more than 1.2cm appeared to be of prognostic value. Patients with bilateral narrowing of the portal vein and collateral veins did not survive for more than 1.5 years after resection. Our own experience indicates that tumour ingrowth may appear t o be of non-carcinomatous origin when the resected specimen is carefully investigated. This is in line with the 40% non-carcinomatous invasion found in colon cancer with adjacent organ involvement (15). So far there are no data available to establish any prognostic value of portal invasion or presence of collateral veins. The presence of lymph node metastases is of prognostic value according to some authors, although others do not confirm this. This is of limited value as a preoperative diagnostic tool because accurate diagnosis is only possible after surgical resection.
INDICATIONS FOR LAPAROTOMY There is an indication for laparotomy if treatment is considered. Surgical treatment for pancreatic cancer is not indicated if distant metastases are present ( N l b , M l ) . In all other cases (any T NO, l a ) a laparotomy should be performed to establish resectability. If the tumour is not resectable and distant metastases are not present, radiotherapy and 5-FUtreatment is given in the unresectable cases. The exact nature of the tumour should be established t o give adequate treatment. The overall cure rate in case of pancreatic tumours may be improved if all treatment options are known to the physician.
REFERENCES 1. Moertel CG, Frytak S , Hahn RG, et al. Therapy of locally unresectable pancreatic carcinoma. Cancer 1981;48:1705-10. 2. Jeekel J, Treurniet-Donker AD. Treatment perspectives in locally advanced unresectable pancreas cancer. Br J Surg 199 1 ;1 1:1331 4 . 3. Treurniet-Donker AD, vanMierlo MJM, vanputten WLJ.
Localized unresectable pancreatic cancer. Int J Radiat Oncol 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;203:77-81. 6. Mannell A, Weiland LH, van Heerden JA, et al. Actors influencing survival after resection for ductal adenocarcinoma of the pancreas. Ann Surg 1986;203:403-7. 7. Nagakawa T, Kanoshi I, Ueno K, et al. Surgical treatment of pancreatic cancer. Int J Pancreatol 1991;9:135-43. 8. Andren-Sandberg A. Factors influencing survival after total
pancreatectomy in patients with pancreatic cancer. Ann Surg 1991;214:605-10. 9. Sato T, Saitoh Y, Noto N, et al. Follow-up studies of radical resection for pancreaticoduodenal cancer. Ann Surg 1977; 186:581-8. 10. Williams J, Cubilla A, Maclean B, et al. Twenty-two year
experience with periampullary carcinoma at Memorial SloanKettering Cancer Center. Am J Surg 1979;138:662-5. 11. Van Heerden JA, McIlrath DC, Ilstrup D, et al. Total pancreatectomy for ductal adenocarcinoma of the pancreas: an update. World J Surg 1988;12:658-62. 12. Klinkenbijl J. Carcinoma of the pancreas and periampullary region, palliation or cure? A review of 310 patients. Br J Surg. 13. Gudjonsson B. Cancer of the pancreas. Cancer 1987;60:2284303. 14. Ishikawa 0, Ohigashi H, Imaoka S , et al. Preoperative indi-
cations for extended pancreatectomy for locally advanced pancreas involving the portal vein. Ann Surg 1992;215:231-6. 15. Kroneman H, Castelein A, Jeekel J. En bloc resection of colon adherent to other organs; an efficacious treatment? Dis Colon Rectum 1991;34:780-3.
