Br. J. Surg. 1991, Vol. 78, November, 1332-1 334
J. Jeekel and A. D. Treurniet-Donker Department of Surgery, University Hospital Dukzigt, Dr. Molewaterplein 40, 3015 GD Rotterdam, The Netherlands Correspondence to: Professor J. Jeekel
Treatment perspectives in locally advanced unresectable pancreatic cancer Locally advanced unresectable pancreatic cancer is sometimes encountered without manifest distant metastases. Twenty patients with histologically proven unresectable pancreatic cancer without distant metastases were treated with radiotherapy and 5-Juorouracil (5-FU). Radiotherapy consisted of 50 Gy external upper abdomen radiation in two courses, concomitant with intravenous 5-FU 375 mg/m2 given as a bolus injection 4-6 h before radiation on the first 4 days of each treatment course. The treatment protocol was completed in 18 patients without complications. The median survival time was 10 months which compares favourably with a 3-5 months median survival time when treatment is withheld. Nine patients (45 per cent) were alive at I year, two patients at 2 , 3 and 4 years. A second-look operation was performed in four patients 6,11,12 and 22 months after completion of radiotherapy. In two patients the tumour could be resected. It appears that treatment with radiotherapy and 5-FU may benefit patients with locally advanced unresectable pancreatic cancer.
Between May 1982 and January 1990, 206 patients were operated on for pancreatic and periampullary cancer at the University Hospital Dijkzigt, Rotterdam. Pancreatic resection was performed in 108 patients. Twenty of the remaining 98 patients had locally advanced unresectable pancreatic cancer without metastases and were treated with combined radiotherapy and 5-FU. In 19 patients irresectability was established at operation. An endoprosthesis was left in situ for drainage of bile in eight patients. A choledochojejunostomy was performed in only five patients and a gastrojejunostomy in six patients. The diagnosis was confirmed by pathological examination in all 20 patients. Radiotherapy and 5-FU treatment were performed in the Dr Daniel den Hoed Cancer Center, Rotterdam. Radiotherapy was given
according to a protocol consisting of a total of 50 Gy external radiation in two couses with intravenous 5-FU 375 mg/m2 given as a bolus injection 4-6 h before radiation on the first 4 days of each treatment course. The daily fraction of radiation was 2 Gy. The interval between the two courses was 3 weeks. Radiation technique involved multiple-field treatment planning using computed tomography. Megavolt energy of 25 MV was preferred, although occasionally 4, 6 or 8 MV was used. The main concern was protection of the kidneys and spinal column. Technical details of the radiotherapy protocol are described by Treurniet-Donker et 01.'. This protocol was developed on the basis of the results of GITSG'-'. The choice of radiation dose of 50 Gy was a compromise between the 40 and 60 Gy doses used in the GITSG study. In order to limit treatment duration in this group of patients with such a limited survival we decided not to give the maintenance 5-FU as used in the GITSG study. In using the dose of 50 Gy in fractions of 2 Gy, actual treatment time was limited to 5 weeks. Half way through this treatment a pause of 3 weeks was considered valuable to allow acute reactions to therapy to subside. Irresectability of the tumour was established during laparotomy when tumour invasion was considered to be present in the hepatoduodenal ligament, in adjacent peritoneum, in the transverse mesocolon, or in a large part of the superior mesenteric vein and/or portal vein. Histopathological confirmation of adenocarcinoma in the pancreas was obtained in all cases. Differentiation between pancreatic duct cancer or periampullary cancer was not possible in these cases. For such a diagnosis, resection specimens are necessary, with information about the exact position of the tumour. The tumour node metastasis (TNM) cancer classification was used with a modification for the N stage. The N,, stage was denoted as a situation in which local peripancreatic lymph nodes contained tumour, whereas regional and distant lymph nodes were free of tumour. N,, indicated the presence of distant lymph node metastases. The TNM staging procedure is depicted in Table 1. In total, 20 patients with histologically proven adenocarcinoma in the pancreas (T,N,-,M,) were treated with radiotherapy and 5-FU. The treatment protocol could be completed in 18 patients. In one patient, radiotherapy treatment was discontinued after 34 Gy because of a deterioration in general condition. In one patient, 5-FU treatment was discontinued during the second course due to leucopenia. In four patients, a second-look operation was performed 6, 11, 12 and 22 months, respectively, after treatment with radiotherapy and 5-FU. Resection of the pancreas was possible in two of these patients. Survival n)as calculated from the date of surgery until May 1991, on an actuarial basis using the Kaplan-Meier method. Death from disease was taken as the endpoint in the study.
1332
0007-1323/91/111332-03
Pancreatic cancer has a dismal prognosis, with a 5-year survival rate of between zero a n d 15 per cent after resection. I n spite of the development of advanced diagnostic procedures, most patients will have locally advanced disease or distant metastases a t the time of diagnosis. In some series distant metastases a n d locally advanced disease are found a t laparotomy in 6cT70 per cent of cases considered potentially resectable. In cases of locally advanced cancer, distant metastases may be absent. It should be stressed that it may be extremely difficult t o assess accurately before, a n d even during, laparotomy whether the tumour arises in the pancreas or periampullary region, and whether invasion of surrounding organs is caused by an inflammatory reaction or tu m o u r infiltration. Treatment is usually withheld from those patients in whom surgical resection is not possible. In other locally invasive digestive tract cancers, such as colonic a n d gastric cancer, distant metastases are not necessarily present and cure can be obtained by adequate local treatment i-4. Since 1982 we have offered treatment with local radiotherapy combined with 5-fluorouracil (5-FU) t o patients with proven unresectable localized pancreatic cancer without signs of distant metastases. Th e value of this combined treatment was suggested by results of the Gastrointestinal T u m o r Study G r o u p (GITSG), which showed better results if 5-FU was combined with radiation the rap^^.^. T h e results of this treatment appear t o be promising, offering the patient the opportunity for long-term survival.
Patients and methods
1991 Butterworth-Heinemann Ltd
Treatment of unresectable pancreatic cancer: J. Jeekel and A.
Table 1 T N M classifcation ,for pancreatic carcinoma Stage ~
Description ~~~
T (primary tumour) Primary tumour cannot be assessed T, No evidence of primary tumour To Tumour limited to the pancreas TI TI,, tumour 2 cm or less in greatest dimension T,,, tumour more than 2 cm in greatest dimension Turnour extends directly to the duodenum, bile duct or T* peripancreatic tissues, still enabling resection Tumour extends directly to the stomach, spleen, colon or T, adjacent large vessels, not enabling resection N (regional lymph nodes) Regional lymph nodes cannot be assessed N x No regional lymph node metastasis N0 Nl Lymph node metastasis N,,, locally in resection specimen N,,, lymph node metastasis regionally outside the resection area
M (distant metastasis) Presence of distant metastasis cannot be assessed M,, N o distant metastasis M, Distant metastasis
M,
Time (months)
Figure 1 Survival,from time of diagnosis at laparotomy of20 patients with locally unresectable pancreatic cancer treated with radiotherapy and 5-Jluorouracil. One patient survived f o r more than 5 years. All patients were followed f o r at least 16 months
Results There were no deaths related to surgery or to treatment with radiotherapy and 5-FU. The treatment protocol was completed in a total of 18 patients without complications. Jaundice occurred in four patients with an endoprosthesis. This was successfully treated by replacement of the endoprosthesis. Reoperation for bile duct obstruction or duodenal obstruction was not necessary in any case. At 1 year, nine (45 per cent) patients were alive. Two patients survived for 2 years and were still alive at 4 years. One patient is alive more than 5 years after diagnosis, but has signs of metastases in the lung (Figure I). A second-look operation was carried out in four patients at 6, 11, 12 and 22 months after completion of radiotherapy in order to resect the tumour remnant. These patients did not have signs of progressive disease and were in good condition. Resection was possible in two of these patients who originally had an irresectable pancreatic cancer. In the other two patients the tumour was still unresectable. Pathological investigation after resection in one of these patients showed a small pancreatic ductal adenocarcinoma measuring 0.5 cm in the head of the pancreas without evidence
Br. J. Surg., Vol. 78, No. 11, November 1991
D.Treurniet-Donker
of lymph node metastases. In the other patient the tumour invaded the duodenum, and local peripancreatic lymph node metastases were found. There were no postoperative complications. The two patients who underwent resection are still alive, although one is the 5-year survivor who now has distant metastases.
Discussion Cure in patients with pancreatic cancer is obtained in only a small percentage of cases, even when a so-called curative resection can be carried out. This has led to a pessimistic approach towards the operative treatment of this condition. At laparotomy the cancer often appears to be inoperable due to metastases or locally advanced disease. At this stage the tumour is generally regarded as incurable and treatment is withheld. This approach can be challenged in patients with locally advanced disease who have no signs of distant metastases. Comparable situations with other carcinomas such as gastric and colonic cancer indicate that tumour growth into surrounding tissue can indeed occur without the occurrence of distant metastases. En bloc resection of such locally advanced cancers can lead to long-term survival'-". In locally advanced pancreatic cancer, en bloc resection is not possible because of the anatomical position of the pancreas. We have treated these irresectable tumours with radiotherapy and 5-FU. Treatment was generally well tolerated and was completed in 18 of 20 patients. The survival rate was 45 per cent at 1 year, and 13 per cent at 2, 3 and 4 years. Median survival time was 10 months. Presently, one patient is alive at more than 5 years after treatment. Other investigators have found a median survival of 9-125 months after combined radiotherapy and chemotherapy in locally unresectable pancreatic cancer5-'", which compares favourably with a median survival of 3-5 months when treatment is withheld. There are reports7.* of 5-year survival after combined treatment with radiotherapy and 5-FU. Survival in our study after treatment with radiotherapy and 5-FU was similar to that of patients with resectable cancer. The median survival time after 'curative' pancreatic resection for pancreatic cancer is, in our experience, 13.3 months in 50 patients; 1-year and 4-year survival rates are 56 and 11 per cent, respectively. This surprising finding may be explained by the assumption that the tumour stage of patients with resectable tumours is similar to this selected group of patients with advanced unresectable cancer but no distant metastases. It is known in colonic cancer that about 40 per cent of adjacent organ involvement appears to be inflammatory. These data are not available for locally invasive pancreatic cancer because resection specimens are not available. In this study, invasion of the tumour into surrounding tissues was usually diagnosed by macroscopic examination during laparotomy. Thus, it may be that some of our patients did not have tumour infiltration, but only inflammatory infiltration around the tumour as a result of pancreatitis, which might explain the favourable survival rate. This is a further reason not to withhold treatment when the tumour appears to be unresectable. It also emphasizes the point that pathological confirmation of carcinoma must be established in order to exclude pancreatitis of the head of the pancreas mimicking a carcinoma. It was our policy to avoid bypass operations during the exploratory laparotomy unless there was obstruction of the bile duct or gastric outlet, because preventive bypass surgery may lead to unnecessary complications and mortality. A reoperation for obstructive symptoms was not necessary in any of the 20 patients. The value of a second-look operation in these patients is shown by the possibility of resection in two of our four patients who had this procedure. The tumour was still present but had reduced to a resectable size. Second-look operations have also been described by Pilepich and Miller'5. They were able to
1333
Treatment of unresectable pancreatic cancer: J. Jeekel and A. D. Treurniet-Donker
perform resection in six patients after preoperative radiation; two of these six patients were still alive after 5 years. We conclude that treatment with radiotherapy and 5-FU in patients with locally advanced irresectable cancer of the pancreas can be achieved with little morbidity and may offer longer survival.
7. 8. 9.
References 1.
2.
3. 4. 5.
6.
Papachristou DN, Shiu MH. Management by en bloc multiple organ resection of carcinoma of the stomach invading adjacent organs. Surg Gynecol Obstet 1988; 152: 483-7. Viste A, Lillestsl J, Ssreide 0.Cancer of the stomach: are curative resections of any importance with respect to postoperative survival in patients with locoregional disease? Int Surg 1984; 69: 133-5. Kroneman H, Castelein A, Jeekel J. En bloc resection of colon carcinoma adherent to other organs: an efficacious treatment? Dis Colon Rectum (in press). Bonfanti G, Bozzetti F, Doci R et a/. Results of extended surgery for cancer ofthe rectum and sigmoid. Br J Surg 1982;69: 305-7. The Gastrointestinal Tumor Study Group. Therapy of locally unresectable pancreatic carcinoma: a randomized comparison of high dose (6000 rads) radiation alone, moderate dose radiation (4000 rads + 5-fluorouracil), and high dose radiation +5fluorouracil. Cancer 1981; 48: 1705-10. The Gastrointestinal Tumor Study Group. A multi-institutional comparative trial of radiation therapy alone and in combination
1334
10. 11.
12. 13. 14.
15.
with 5-fluorouracil for locally unresectable pancreatic carcinoma. Ann Surg 1979; 189: 205-8. Treurniet-Donker AD, van Mierlo MJM, van Putten WLJ. Localized unresectable pancreatic cancer. Int J Radiat Oncol Bid P h v ~1990; 18: 59-62. Dobelbower RR, Borgelt BB, Suntharalingam N, Strubler KA. Pancreatic carcinoma treated with high-dose small-volume irradiation. Cancer 1978; 41: 1087-97. Falk RE, Moffat FL, Lawler M, Heine J, Makowka L, Falk JA. Combination therapy for resectable and unresectable adenocarcinoma of the pancreas. Cancer 1986; 57: 685-8. Selch MT, Parker RG. Results in the management of locally unresected pancreatic carcinoma. Am J CIin Oncol 1986; 9: 13945. Mohiuddin M, Cantor RJ, Bierman W, Weiss SM, Barbot D, Rosato FE. Combined modality treatment of localized unresectable adenocarcinoma of the pancreas. Znr J Radiar Oncol Biol Phys 1988; 14: 79-84. Whittington R, Solin L, Mohiuddin M et al. Multimodality therapy of localized unresectable pancreatic adenocarcinoma. Cancer 1984; 54: 1991-8. Battle Haslam J, Cavanough PJ, Stroup SL. Radiation therapy in the treatment of irresectable adenocarcinoma of the pancreas. Cancer 1973; 32: 1341-5. McCracken JD, Ray P, Heilbrun L el a/. 5-Fluorouracil, methyl-CCNU, and radiotherapy with or without testolactone for localized adenocarcinoma of the exocrine pancreas. A Southwest Oncology Group Study. Cancer 1980; 46: 1518-22. Pilepich MV, Miller HH. Preoperative irradiation in carcinoma of the pancreas. Cancer 1989; 46: 1945-9.
Paper accepted 24 July 1991
Br. J. Surg., Vol. 78, No. 11, November 1991
J. Jeekel and A. D. Treurniet-Donker Department of Surgery, University Hospital Dukzigt, Dr. Molewaterplein 40, 3015 GD Rotterdam, The Netherlands Correspondence to: Professor J. Jeekel
Treatment perspectives in locally advanced unresectable pancreatic cancer Locally advanced unresectable pancreatic cancer is sometimes encountered without manifest distant metastases. Twenty patients with histologically proven unresectable pancreatic cancer without distant metastases were treated with radiotherapy and 5-Juorouracil (5-FU). Radiotherapy consisted of 50 Gy external upper abdomen radiation in two courses, concomitant with intravenous 5-FU 375 mg/m2 given as a bolus injection 4-6 h before radiation on the first 4 days of each treatment course. The treatment protocol was completed in 18 patients without complications. The median survival time was 10 months which compares favourably with a 3-5 months median survival time when treatment is withheld. Nine patients (45 per cent) were alive at I year, two patients at 2 , 3 and 4 years. A second-look operation was performed in four patients 6,11,12 and 22 months after completion of radiotherapy. In two patients the tumour could be resected. It appears that treatment with radiotherapy and 5-FU may benefit patients with locally advanced unresectable pancreatic cancer.
Between May 1982 and January 1990, 206 patients were operated on for pancreatic and periampullary cancer at the University Hospital Dijkzigt, Rotterdam. Pancreatic resection was performed in 108 patients. Twenty of the remaining 98 patients had locally advanced unresectable pancreatic cancer without metastases and were treated with combined radiotherapy and 5-FU. In 19 patients irresectability was established at operation. An endoprosthesis was left in situ for drainage of bile in eight patients. A choledochojejunostomy was performed in only five patients and a gastrojejunostomy in six patients. The diagnosis was confirmed by pathological examination in all 20 patients. Radiotherapy and 5-FU treatment were performed in the Dr Daniel den Hoed Cancer Center, Rotterdam. Radiotherapy was given
according to a protocol consisting of a total of 50 Gy external radiation in two couses with intravenous 5-FU 375 mg/m2 given as a bolus injection 4-6 h before radiation on the first 4 days of each treatment course. The daily fraction of radiation was 2 Gy. The interval between the two courses was 3 weeks. Radiation technique involved multiple-field treatment planning using computed tomography. Megavolt energy of 25 MV was preferred, although occasionally 4, 6 or 8 MV was used. The main concern was protection of the kidneys and spinal column. Technical details of the radiotherapy protocol are described by Treurniet-Donker et 01.'. This protocol was developed on the basis of the results of GITSG'-'. The choice of radiation dose of 50 Gy was a compromise between the 40 and 60 Gy doses used in the GITSG study. In order to limit treatment duration in this group of patients with such a limited survival we decided not to give the maintenance 5-FU as used in the GITSG study. In using the dose of 50 Gy in fractions of 2 Gy, actual treatment time was limited to 5 weeks. Half way through this treatment a pause of 3 weeks was considered valuable to allow acute reactions to therapy to subside. Irresectability of the tumour was established during laparotomy when tumour invasion was considered to be present in the hepatoduodenal ligament, in adjacent peritoneum, in the transverse mesocolon, or in a large part of the superior mesenteric vein and/or portal vein. Histopathological confirmation of adenocarcinoma in the pancreas was obtained in all cases. Differentiation between pancreatic duct cancer or periampullary cancer was not possible in these cases. For such a diagnosis, resection specimens are necessary, with information about the exact position of the tumour. The tumour node metastasis (TNM) cancer classification was used with a modification for the N stage. The N,, stage was denoted as a situation in which local peripancreatic lymph nodes contained tumour, whereas regional and distant lymph nodes were free of tumour. N,, indicated the presence of distant lymph node metastases. The TNM staging procedure is depicted in Table 1. In total, 20 patients with histologically proven adenocarcinoma in the pancreas (T,N,-,M,) were treated with radiotherapy and 5-FU. The treatment protocol could be completed in 18 patients. In one patient, radiotherapy treatment was discontinued after 34 Gy because of a deterioration in general condition. In one patient, 5-FU treatment was discontinued during the second course due to leucopenia. In four patients, a second-look operation was performed 6, 11, 12 and 22 months, respectively, after treatment with radiotherapy and 5-FU. Resection of the pancreas was possible in two of these patients. Survival n)as calculated from the date of surgery until May 1991, on an actuarial basis using the Kaplan-Meier method. Death from disease was taken as the endpoint in the study.
1332
0007-1323/91/111332-03
Pancreatic cancer has a dismal prognosis, with a 5-year survival rate of between zero a n d 15 per cent after resection. I n spite of the development of advanced diagnostic procedures, most patients will have locally advanced disease or distant metastases a t the time of diagnosis. In some series distant metastases a n d locally advanced disease are found a t laparotomy in 6cT70 per cent of cases considered potentially resectable. In cases of locally advanced cancer, distant metastases may be absent. It should be stressed that it may be extremely difficult t o assess accurately before, a n d even during, laparotomy whether the tumour arises in the pancreas or periampullary region, and whether invasion of surrounding organs is caused by an inflammatory reaction or tu m o u r infiltration. Treatment is usually withheld from those patients in whom surgical resection is not possible. In other locally invasive digestive tract cancers, such as colonic a n d gastric cancer, distant metastases are not necessarily present and cure can be obtained by adequate local treatment i-4. Since 1982 we have offered treatment with local radiotherapy combined with 5-fluorouracil (5-FU) t o patients with proven unresectable localized pancreatic cancer without signs of distant metastases. Th e value of this combined treatment was suggested by results of the Gastrointestinal T u m o r Study G r o u p (GITSG), which showed better results if 5-FU was combined with radiation the rap^^.^. T h e results of this treatment appear t o be promising, offering the patient the opportunity for long-term survival.
Patients and methods
1991 Butterworth-Heinemann Ltd
Treatment of unresectable pancreatic cancer: J. Jeekel and A.
Table 1 T N M classifcation ,for pancreatic carcinoma Stage ~
Description ~~~
T (primary tumour) Primary tumour cannot be assessed T, No evidence of primary tumour To Tumour limited to the pancreas TI TI,, tumour 2 cm or less in greatest dimension T,,, tumour more than 2 cm in greatest dimension Turnour extends directly to the duodenum, bile duct or T* peripancreatic tissues, still enabling resection Tumour extends directly to the stomach, spleen, colon or T, adjacent large vessels, not enabling resection N (regional lymph nodes) Regional lymph nodes cannot be assessed N x No regional lymph node metastasis N0 Nl Lymph node metastasis N,,, locally in resection specimen N,,, lymph node metastasis regionally outside the resection area
M (distant metastasis) Presence of distant metastasis cannot be assessed M,, N o distant metastasis M, Distant metastasis
M,
Time (months)
Figure 1 Survival,from time of diagnosis at laparotomy of20 patients with locally unresectable pancreatic cancer treated with radiotherapy and 5-Jluorouracil. One patient survived f o r more than 5 years. All patients were followed f o r at least 16 months
Results There were no deaths related to surgery or to treatment with radiotherapy and 5-FU. The treatment protocol was completed in a total of 18 patients without complications. Jaundice occurred in four patients with an endoprosthesis. This was successfully treated by replacement of the endoprosthesis. Reoperation for bile duct obstruction or duodenal obstruction was not necessary in any case. At 1 year, nine (45 per cent) patients were alive. Two patients survived for 2 years and were still alive at 4 years. One patient is alive more than 5 years after diagnosis, but has signs of metastases in the lung (Figure I). A second-look operation was carried out in four patients at 6, 11, 12 and 22 months after completion of radiotherapy in order to resect the tumour remnant. These patients did not have signs of progressive disease and were in good condition. Resection was possible in two of these patients who originally had an irresectable pancreatic cancer. In the other two patients the tumour was still unresectable. Pathological investigation after resection in one of these patients showed a small pancreatic ductal adenocarcinoma measuring 0.5 cm in the head of the pancreas without evidence
Br. J. Surg., Vol. 78, No. 11, November 1991
D.Treurniet-Donker
of lymph node metastases. In the other patient the tumour invaded the duodenum, and local peripancreatic lymph node metastases were found. There were no postoperative complications. The two patients who underwent resection are still alive, although one is the 5-year survivor who now has distant metastases.
Discussion Cure in patients with pancreatic cancer is obtained in only a small percentage of cases, even when a so-called curative resection can be carried out. This has led to a pessimistic approach towards the operative treatment of this condition. At laparotomy the cancer often appears to be inoperable due to metastases or locally advanced disease. At this stage the tumour is generally regarded as incurable and treatment is withheld. This approach can be challenged in patients with locally advanced disease who have no signs of distant metastases. Comparable situations with other carcinomas such as gastric and colonic cancer indicate that tumour growth into surrounding tissue can indeed occur without the occurrence of distant metastases. En bloc resection of such locally advanced cancers can lead to long-term survival'-". In locally advanced pancreatic cancer, en bloc resection is not possible because of the anatomical position of the pancreas. We have treated these irresectable tumours with radiotherapy and 5-FU. Treatment was generally well tolerated and was completed in 18 of 20 patients. The survival rate was 45 per cent at 1 year, and 13 per cent at 2, 3 and 4 years. Median survival time was 10 months. Presently, one patient is alive at more than 5 years after treatment. Other investigators have found a median survival of 9-125 months after combined radiotherapy and chemotherapy in locally unresectable pancreatic cancer5-'", which compares favourably with a median survival of 3-5 months when treatment is withheld. There are reports7.* of 5-year survival after combined treatment with radiotherapy and 5-FU. Survival in our study after treatment with radiotherapy and 5-FU was similar to that of patients with resectable cancer. The median survival time after 'curative' pancreatic resection for pancreatic cancer is, in our experience, 13.3 months in 50 patients; 1-year and 4-year survival rates are 56 and 11 per cent, respectively. This surprising finding may be explained by the assumption that the tumour stage of patients with resectable tumours is similar to this selected group of patients with advanced unresectable cancer but no distant metastases. It is known in colonic cancer that about 40 per cent of adjacent organ involvement appears to be inflammatory. These data are not available for locally invasive pancreatic cancer because resection specimens are not available. In this study, invasion of the tumour into surrounding tissues was usually diagnosed by macroscopic examination during laparotomy. Thus, it may be that some of our patients did not have tumour infiltration, but only inflammatory infiltration around the tumour as a result of pancreatitis, which might explain the favourable survival rate. This is a further reason not to withhold treatment when the tumour appears to be unresectable. It also emphasizes the point that pathological confirmation of carcinoma must be established in order to exclude pancreatitis of the head of the pancreas mimicking a carcinoma. It was our policy to avoid bypass operations during the exploratory laparotomy unless there was obstruction of the bile duct or gastric outlet, because preventive bypass surgery may lead to unnecessary complications and mortality. A reoperation for obstructive symptoms was not necessary in any of the 20 patients. The value of a second-look operation in these patients is shown by the possibility of resection in two of our four patients who had this procedure. The tumour was still present but had reduced to a resectable size. Second-look operations have also been described by Pilepich and Miller'5. They were able to
1333
Treatment of unresectable pancreatic cancer: J. Jeekel and A. D. Treurniet-Donker
perform resection in six patients after preoperative radiation; two of these six patients were still alive after 5 years. We conclude that treatment with radiotherapy and 5-FU in patients with locally advanced irresectable cancer of the pancreas can be achieved with little morbidity and may offer longer survival.
7. 8. 9.
References 1.
2.
3. 4. 5.
6.
Papachristou DN, Shiu MH. Management by en bloc multiple organ resection of carcinoma of the stomach invading adjacent organs. Surg Gynecol Obstet 1988; 152: 483-7. Viste A, Lillestsl J, Ssreide 0.Cancer of the stomach: are curative resections of any importance with respect to postoperative survival in patients with locoregional disease? Int Surg 1984; 69: 133-5. Kroneman H, Castelein A, Jeekel J. En bloc resection of colon carcinoma adherent to other organs: an efficacious treatment? Dis Colon Rectum (in press). Bonfanti G, Bozzetti F, Doci R et a/. Results of extended surgery for cancer ofthe rectum and sigmoid. Br J Surg 1982;69: 305-7. The Gastrointestinal Tumor Study Group. Therapy of locally unresectable pancreatic carcinoma: a randomized comparison of high dose (6000 rads) radiation alone, moderate dose radiation (4000 rads + 5-fluorouracil), and high dose radiation +5fluorouracil. Cancer 1981; 48: 1705-10. The Gastrointestinal Tumor Study Group. A multi-institutional comparative trial of radiation therapy alone and in combination
1334
10. 11.
12. 13. 14.
15.
with 5-fluorouracil for locally unresectable pancreatic carcinoma. Ann Surg 1979; 189: 205-8. Treurniet-Donker AD, van Mierlo MJM, van Putten WLJ. Localized unresectable pancreatic cancer. Int J Radiat Oncol Bid P h v ~1990; 18: 59-62. Dobelbower RR, Borgelt BB, Suntharalingam N, Strubler KA. Pancreatic carcinoma treated with high-dose small-volume irradiation. Cancer 1978; 41: 1087-97. Falk RE, Moffat FL, Lawler M, Heine J, Makowka L, Falk JA. Combination therapy for resectable and unresectable adenocarcinoma of the pancreas. Cancer 1986; 57: 685-8. Selch MT, Parker RG. Results in the management of locally unresected pancreatic carcinoma. Am J CIin Oncol 1986; 9: 13945. Mohiuddin M, Cantor RJ, Bierman W, Weiss SM, Barbot D, Rosato FE. Combined modality treatment of localized unresectable adenocarcinoma of the pancreas. Znr J Radiar Oncol Biol Phys 1988; 14: 79-84. Whittington R, Solin L, Mohiuddin M et al. Multimodality therapy of localized unresectable pancreatic adenocarcinoma. Cancer 1984; 54: 1991-8. Battle Haslam J, Cavanough PJ, Stroup SL. Radiation therapy in the treatment of irresectable adenocarcinoma of the pancreas. Cancer 1973; 32: 1341-5. McCracken JD, Ray P, Heilbrun L el a/. 5-Fluorouracil, methyl-CCNU, and radiotherapy with or without testolactone for localized adenocarcinoma of the exocrine pancreas. A Southwest Oncology Group Study. Cancer 1980; 46: 1518-22. Pilepich MV, Miller HH. Preoperative irradiation in carcinoma of the pancreas. Cancer 1989; 46: 1945-9.
Paper accepted 24 July 1991
Br. J. Surg., Vol. 78, No. 11, November 1991
