Scandinavian Journal of Gastroenterology
ISSN: 0036-5521 (Print) 1502-7708 (Online) Journal homepage: http://www.tandfonline.com/loi/igas20
Perioperative Blood Transfusion and Recurrence and Death after Resection for Cancer of the Colon and Rectum E. B. Jakobsen, J. H. Eickhoff, J. Andersen, L. Lundvall & J. K. Stenderup To cite this article: E. B. Jakobsen, J. H. Eickhoff, J. Andersen, L. Lundvall & J. K. Stenderup (1990) Perioperative Blood Transfusion and Recurrence and Death after Resection for Cancer of the Colon and Rectum, Scandinavian Journal of Gastroenterology, 25:5, 435-442, DOI: 10.3109/00365529009095512 To link to this article: http://dx.doi.org/10.3109/00365529009095512
Published online: 08 Jul 2009.
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Date: 08 April 2016, At: 20:38
Perioperative Blood Transfusion and Recurrence and Death after Resection for Cancer of the Colon and Rectum
Downloaded by [RMIT University Library] at 20:38 08 April 2016
E.B. JAKOBSEN, J.H. EICKHOFF. J. ANDERSEN, L. LUNDVALL & J.K. STENDERUP Dept. of Surgery K, Frederiksberg Hospital, Frederiksberg, and Dept. of Surgical Gastroenterology D. Gentofte Hospital, Copenhagen, Denmark Jakobsen EB, Eickhoff JH, Andersen J, Lundvall L, Stenderup JK. Perioperative blood transfusion and recurrence and death after resection for cancer of the colon and rectum. Scand J Gastroenterol 1990, 25, 435-442 Several reports have claimed that perioperative blood transfusion promotes recurrence and death after cancer surgery. We studied the effect of transfusion in 315 patients who had radical resection for carcinoma of the colon and rectum. The disease recurred in 113 (42%) of 268 transfused patients, versus in 15 (32%) in 47 nontransfused patients ( P = 0.2). Of the transfused patients 102 (38%) died of colon cancer, versus 13 patients (28%) in the non-transfused group ( P = 0.2). The 5-year recurrence-free survival rate was 0.59 in the transfused patients and 0.72 in the nontransfused group ( P = 0.10). When differences in confounding background variables were accounted for by Cox multiple regression analysis. the significance of transfusion was even less. The study does not support the hypothesis that perioperative blood transfusion promotes recurrence after operation for colorectal cancer.
Key words: Blood transfusion; colon cancer; death; malignant neoplasm; operation; prognosis; rectum cancer; recurrence; surgery; survival Jew H . Eickhoff, M . D . , 16 Ved Ermelunden, DK-2820 Gentofte, Denmark
In recent years several papers have demonstrated a detrimental effect of perioperative blood transfusion on survival after cancer surgery. This effect has been extensively studied in patients with colorectal cancer (1-16). The results are contradictory, but the alarming fact remains that in some studies the relative risks of transfusion on recurrence of and death from this tumor have been reported to be as high as a factor four (3). The aim of this paper is to test the hypothesis that perioperative blood transfusion increases the recurrence rate after curative resection for colon and rectal cancer by reporting complete longterm follow-up data. MATERIALS AND METHODS Patients The study is a retrospective analysis of the
patients who during the years 1978, 1979, 1980, and 1981 had curative resection of the colon or rectum performed in the Dept. of Surgery K, Frederiksberg Hospital, or in the Dept. of Surgical Gastroenterology D, Gentofte Hospital, Copenhagen. Both hospitals are public hospitals, serving about 80,000 and 180,000 inhabitants, respectively, in the central and suburban Copenhagen area. The data bases of the two hospitals contained data on approximately 600 patients operated on for colon cancer. About 120 had previously been operated on for colon cancer, and about 60 had had exploratory or decompression procedures only. In 10 patients histologic proof was lacking. In the other 443 patients, 130 operations were considered palliative only, because of liver metastasis (63 cases), peritoneal carcinosis (25 cases), distant metastasis (20 cases), or unresectable invasion into neighbouring organs or into
436
E. B. Jakobsen et al.
Downloaded by [RMIT University Library] at 20:38 08 April 2016
the abdominal wall (22 cases). In one patient a solitary liver metastasis was later removed, and in another patient a solitary pulmonary metastasis was resected. Thus 315 patients, in whom the operation was considered radical, were eligible for analysis.
Methods The records of the patients were reviewed for the relevant clinical and surgical data. The recorded variables are shown in Tables I and 11. The number and type of transfusions given perioperatively (that is, 1-30 days from the day of operation) were taken from the transfusion records. Transfusions were given at the discretion of the surgeon or the anesthesiologist. The blood bank services at the two hospitals were supervised by the same blood-type serologist, and the banks
delivered the same range of products. The pathology data were taken from the original pathology reports. A simplified Dukes classification consisting of three groups only (A, B, and C) was applied. Adjuvant therapy was given but rarely and for symptomatic recurrences only. Fivefluorouracil was given to young patients with liver metastasis, and radiotherapy was given for painful recurrences in the pelvis in all age groups. Both departments ran regular follow-up schemes including endoscopic and radiologic studies. As a result, most recurrences were diagnosed by the departments. Thus, for most patients accurate and detailed follow-up data were available. In all remaining patients follow-up data were obtained from the records of other hospitals or private physicians or from the patients themselves. Follow-up study was conducted from
Table I. Clinical details in 315 patients radically resected for carcinoma of the colon or rectum, by department Frederiksberg Hospital ( n = 125) Age (years) Sex Men Women Localization Cecum Ascending colon Transverse colon Descending colon Sigmoid colon Rectum Dukes classification A B C Spread of tumor Invasion abdominal wall Invasion other organ Carcinosis Liver metastasis Other metastasis Preoperative hemoglobin (mmol/l) Transfused patients Duration of operation (min) Adjuvant therapy Radiotherapy Chemotherapy
* Mann-Whitney test. t Chi-square test. $ Number too small formeaningful analysis.
Gentofte Hospital (n = 190)
P
70 (41-89)
67 (35-93)
0.05*
62 63
95 95
0.9t
8 14 13 6 45 39
19 17 13 17 60 64
0.4t
26 67 32
14 99 77
0.0004t
2 2
0 0 0 7.9 (3.3-11.1) 110 172 (95-360) 7 2
3 5 0 1 1 8.3 (4.1-14.4) 158 133 (45-360) 11 14
-e 0.02* 0.23t 0.01* 0.77 0.07t
Transfusion and Cancer of Colon and Rectum
431
Table 11. Type and number of transfusions given in 268 patients
No. of units
Downloaded by [RMIT University Library] at 20:38 08 April 2016
Whole blood Packed blood Washed erythrocytes Plasma Plasma concentrate Any type
1
2
3
4
5
610
10
O . 2 ) . Most patients had received blood transfusion, the percentages being 88% and 83%, respectively. The distribution of the various blood products given was almost identical in the two hospitals. Thirty per cent had received one or two transfusions only, and 33% had received six or more units (Table 11). No patient was lost to follow-up study. At follow-up after a median observation time of 9 years two-thirds of the patients had died, half of them of colon cancer (Table 111). Kaplan-Meier plots and log-rank tests showed that all three survival indicators were affected by Dukes stage, localization of tumor, and transfusion. Survival
was not affected by department, age, sex, preoperative hemoglobin, or duration of operation. The clinical details, by transfusion state, are shown in Table IV. The median preoperative hemoglobin value was 0.5mmol/l lower in the transfused group, and the operation time was longer than in the non-transfused patients. The transfused patients more often had rectal extirpation or excision, more seldom had resection of the sigmoid colon, and had more Dukes C tumors than the non-transfused patients. At follow-up study 38% in the transfused group had died of colon cancer versus 28% in the nontransfused group (P = 0.2). The mortality from other cancers was also higher in the transfused group, 9% versus 0% among the non-transfused (P = 0.07). For all unadjusted survival rates studied the transfused patients tended to have a worse prognosis (overall survival rate, Fig. 1; colon
Table IV. Clinical details for 315 patients radically resected for colorectal cancer, by transfusion state Transfused (n = 268) Age (years) Sex Men Women Localization Cecum Ascending colon Transverse colon Descending colon Sigmoid colon Rectum Dukes classification A B C Spread of tumor Invasion abdominal wall Invasion other organ Carcinosis Liver metastasis Other metastasis Prcoperative hemoglobin (mmol/l) Duration of operation (min) Adjuvant therapy Radiotherapy Chemotherapy
* Mann-Whitney test.
t Chi-square test.
$ Number too small for meaningful analysis.
69 (35-93)
Non-transfused (n = 47)
P
66 (41-90)
0.07*
132 136
25 22
0.6t
26 28 22 21 74 97
1 3 4 2 31 6
0.0001~
33 138 97
7 28 12
0.36t
5 7 0 1 1 8.1 (3.3-14.4) 153 (65-385) 16 13
0 0 0 0 0 8.6 (4.1-10.6) 120 (45-360) 0
2
-$
0.01 0.01
-
439
Transfusion and Cancer of Colon and Rectum
oo ,
A
Recurrence-free survival
Downloaded by [RMIT University Library] at 20:38 08 April 2016
i\ \
5
00
10 years
Fig. 1. Unadjusted overall survival rates in 268 transfused and in 47 non-transfused patients.
cancer-specific survival rate, Fig. 2; and recurrence-free survival rate, Fig. 3). However, none of the differences were statistically significant ( P = 0.07, P = 0.10, and P = 0.10, respectively). When recurrence-free survival was calculated in accordance with the number of transfusions given, a confusing pattern was found. Patients receiving 1 4 units had an unadjusted survival rate similar to that of non-transfused patients.
Non -transfused
o0
P = 0.10
10 years w
5
Fig. 3. Unadjusted recurrence-free survival rates in 268 transfused and in 47 non-transfused patients.
Patients receiving 5-10 units had a poorer prognosis, but patients receiving more than 10units had a prognosis comparable to that of the nontransfused (Fig. 4). Cox multiple regression analysis of the colon cancer-specific survival showed that statistically significant variables were Dukes classification and tumor localization, whereas the other factors,
Recurrence-free survival
A
o/o
1o
IZL
Colon cancer specific survival
o h
]
n\-
transfused
0
>. l o
1 -5
Tra n sf used
50
-
P = 0.10
-I 0
0
0
5
5
10 years
Fig. 2. Unadjusted colon cancer-specific survival rates in 268 transfused and in 47 non-transfused patients.
L
B
5
-
1
0
10 years
Fig. 4. Unadjusted recurrence-free survival rates in 47 non-transfused patients and in 268 transfused, by number of transfusions. 172 patients received 1-5 units, 72 patients received 6 1 0 units. and 19 patients received more than 10 units.
440
E . B . Jakobsen et al.
Table V. Result of Cox multiple regression analysis of colon cancer-specificsurvival Regression coefficient
SD
0.0077 0.208 0.0034 -0.0076
0.225 0.203 0.009 0.083
0.034 1.02 0.38 0.092
-1.919 -1.029
0.445 0.207
4.31 4.97
0.372 0.292 0.272 0.002 0.342
1.06 0.35 2.01 1.00 0.96
Downloaded by [RMIT University Library] at 20:38 08 April 2016
Center Sex Age Hemoglobin level Dukes A versus C B versus C Localization Cecum versus ATD* Sigmoid versus ATD* Rectum versus ATD* Duration of operation Transfusion
0.393 0.102 0.546 0.002 0.327
2
P 0.97 0.31 0.70 0.93 0.00002
ISSN: 0036-5521 (Print) 1502-7708 (Online) Journal homepage: http://www.tandfonline.com/loi/igas20
Perioperative Blood Transfusion and Recurrence and Death after Resection for Cancer of the Colon and Rectum E. B. Jakobsen, J. H. Eickhoff, J. Andersen, L. Lundvall & J. K. Stenderup To cite this article: E. B. Jakobsen, J. H. Eickhoff, J. Andersen, L. Lundvall & J. K. Stenderup (1990) Perioperative Blood Transfusion and Recurrence and Death after Resection for Cancer of the Colon and Rectum, Scandinavian Journal of Gastroenterology, 25:5, 435-442, DOI: 10.3109/00365529009095512 To link to this article: http://dx.doi.org/10.3109/00365529009095512
Published online: 08 Jul 2009.
Submit your article to this journal
Article views: 5
View related articles
Citing articles: 1 View citing articles
Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=igas20 Download by: [RMIT University Library]
Date: 08 April 2016, At: 20:38
Perioperative Blood Transfusion and Recurrence and Death after Resection for Cancer of the Colon and Rectum
Downloaded by [RMIT University Library] at 20:38 08 April 2016
E.B. JAKOBSEN, J.H. EICKHOFF. J. ANDERSEN, L. LUNDVALL & J.K. STENDERUP Dept. of Surgery K, Frederiksberg Hospital, Frederiksberg, and Dept. of Surgical Gastroenterology D. Gentofte Hospital, Copenhagen, Denmark Jakobsen EB, Eickhoff JH, Andersen J, Lundvall L, Stenderup JK. Perioperative blood transfusion and recurrence and death after resection for cancer of the colon and rectum. Scand J Gastroenterol 1990, 25, 435-442 Several reports have claimed that perioperative blood transfusion promotes recurrence and death after cancer surgery. We studied the effect of transfusion in 315 patients who had radical resection for carcinoma of the colon and rectum. The disease recurred in 113 (42%) of 268 transfused patients, versus in 15 (32%) in 47 nontransfused patients ( P = 0.2). Of the transfused patients 102 (38%) died of colon cancer, versus 13 patients (28%) in the non-transfused group ( P = 0.2). The 5-year recurrence-free survival rate was 0.59 in the transfused patients and 0.72 in the nontransfused group ( P = 0.10). When differences in confounding background variables were accounted for by Cox multiple regression analysis. the significance of transfusion was even less. The study does not support the hypothesis that perioperative blood transfusion promotes recurrence after operation for colorectal cancer.
Key words: Blood transfusion; colon cancer; death; malignant neoplasm; operation; prognosis; rectum cancer; recurrence; surgery; survival Jew H . Eickhoff, M . D . , 16 Ved Ermelunden, DK-2820 Gentofte, Denmark
In recent years several papers have demonstrated a detrimental effect of perioperative blood transfusion on survival after cancer surgery. This effect has been extensively studied in patients with colorectal cancer (1-16). The results are contradictory, but the alarming fact remains that in some studies the relative risks of transfusion on recurrence of and death from this tumor have been reported to be as high as a factor four (3). The aim of this paper is to test the hypothesis that perioperative blood transfusion increases the recurrence rate after curative resection for colon and rectal cancer by reporting complete longterm follow-up data. MATERIALS AND METHODS Patients The study is a retrospective analysis of the
patients who during the years 1978, 1979, 1980, and 1981 had curative resection of the colon or rectum performed in the Dept. of Surgery K, Frederiksberg Hospital, or in the Dept. of Surgical Gastroenterology D, Gentofte Hospital, Copenhagen. Both hospitals are public hospitals, serving about 80,000 and 180,000 inhabitants, respectively, in the central and suburban Copenhagen area. The data bases of the two hospitals contained data on approximately 600 patients operated on for colon cancer. About 120 had previously been operated on for colon cancer, and about 60 had had exploratory or decompression procedures only. In 10 patients histologic proof was lacking. In the other 443 patients, 130 operations were considered palliative only, because of liver metastasis (63 cases), peritoneal carcinosis (25 cases), distant metastasis (20 cases), or unresectable invasion into neighbouring organs or into
436
E. B. Jakobsen et al.
Downloaded by [RMIT University Library] at 20:38 08 April 2016
the abdominal wall (22 cases). In one patient a solitary liver metastasis was later removed, and in another patient a solitary pulmonary metastasis was resected. Thus 315 patients, in whom the operation was considered radical, were eligible for analysis.
Methods The records of the patients were reviewed for the relevant clinical and surgical data. The recorded variables are shown in Tables I and 11. The number and type of transfusions given perioperatively (that is, 1-30 days from the day of operation) were taken from the transfusion records. Transfusions were given at the discretion of the surgeon or the anesthesiologist. The blood bank services at the two hospitals were supervised by the same blood-type serologist, and the banks
delivered the same range of products. The pathology data were taken from the original pathology reports. A simplified Dukes classification consisting of three groups only (A, B, and C) was applied. Adjuvant therapy was given but rarely and for symptomatic recurrences only. Fivefluorouracil was given to young patients with liver metastasis, and radiotherapy was given for painful recurrences in the pelvis in all age groups. Both departments ran regular follow-up schemes including endoscopic and radiologic studies. As a result, most recurrences were diagnosed by the departments. Thus, for most patients accurate and detailed follow-up data were available. In all remaining patients follow-up data were obtained from the records of other hospitals or private physicians or from the patients themselves. Follow-up study was conducted from
Table I. Clinical details in 315 patients radically resected for carcinoma of the colon or rectum, by department Frederiksberg Hospital ( n = 125) Age (years) Sex Men Women Localization Cecum Ascending colon Transverse colon Descending colon Sigmoid colon Rectum Dukes classification A B C Spread of tumor Invasion abdominal wall Invasion other organ Carcinosis Liver metastasis Other metastasis Preoperative hemoglobin (mmol/l) Transfused patients Duration of operation (min) Adjuvant therapy Radiotherapy Chemotherapy
* Mann-Whitney test. t Chi-square test. $ Number too small formeaningful analysis.
Gentofte Hospital (n = 190)
P
70 (41-89)
67 (35-93)
0.05*
62 63
95 95
0.9t
8 14 13 6 45 39
19 17 13 17 60 64
0.4t
26 67 32
14 99 77
0.0004t
2 2
0 0 0 7.9 (3.3-11.1) 110 172 (95-360) 7 2
3 5 0 1 1 8.3 (4.1-14.4) 158 133 (45-360) 11 14
-e 0.02* 0.23t 0.01* 0.77 0.07t
Transfusion and Cancer of Colon and Rectum
431
Table 11. Type and number of transfusions given in 268 patients
No. of units
Downloaded by [RMIT University Library] at 20:38 08 April 2016
Whole blood Packed blood Washed erythrocytes Plasma Plasma concentrate Any type
1
2
3
4
5
610
10
O . 2 ) . Most patients had received blood transfusion, the percentages being 88% and 83%, respectively. The distribution of the various blood products given was almost identical in the two hospitals. Thirty per cent had received one or two transfusions only, and 33% had received six or more units (Table 11). No patient was lost to follow-up study. At follow-up after a median observation time of 9 years two-thirds of the patients had died, half of them of colon cancer (Table 111). Kaplan-Meier plots and log-rank tests showed that all three survival indicators were affected by Dukes stage, localization of tumor, and transfusion. Survival
was not affected by department, age, sex, preoperative hemoglobin, or duration of operation. The clinical details, by transfusion state, are shown in Table IV. The median preoperative hemoglobin value was 0.5mmol/l lower in the transfused group, and the operation time was longer than in the non-transfused patients. The transfused patients more often had rectal extirpation or excision, more seldom had resection of the sigmoid colon, and had more Dukes C tumors than the non-transfused patients. At follow-up study 38% in the transfused group had died of colon cancer versus 28% in the nontransfused group (P = 0.2). The mortality from other cancers was also higher in the transfused group, 9% versus 0% among the non-transfused (P = 0.07). For all unadjusted survival rates studied the transfused patients tended to have a worse prognosis (overall survival rate, Fig. 1; colon
Table IV. Clinical details for 315 patients radically resected for colorectal cancer, by transfusion state Transfused (n = 268) Age (years) Sex Men Women Localization Cecum Ascending colon Transverse colon Descending colon Sigmoid colon Rectum Dukes classification A B C Spread of tumor Invasion abdominal wall Invasion other organ Carcinosis Liver metastasis Other metastasis Prcoperative hemoglobin (mmol/l) Duration of operation (min) Adjuvant therapy Radiotherapy Chemotherapy
* Mann-Whitney test.
t Chi-square test.
$ Number too small for meaningful analysis.
69 (35-93)
Non-transfused (n = 47)
P
66 (41-90)
0.07*
132 136
25 22
0.6t
26 28 22 21 74 97
1 3 4 2 31 6
0.0001~
33 138 97
7 28 12
0.36t
5 7 0 1 1 8.1 (3.3-14.4) 153 (65-385) 16 13
0 0 0 0 0 8.6 (4.1-10.6) 120 (45-360) 0
2
-$
0.01 0.01
-
439
Transfusion and Cancer of Colon and Rectum
oo ,
A
Recurrence-free survival
Downloaded by [RMIT University Library] at 20:38 08 April 2016
i\ \
5
00
10 years
Fig. 1. Unadjusted overall survival rates in 268 transfused and in 47 non-transfused patients.
cancer-specific survival rate, Fig. 2; and recurrence-free survival rate, Fig. 3). However, none of the differences were statistically significant ( P = 0.07, P = 0.10, and P = 0.10, respectively). When recurrence-free survival was calculated in accordance with the number of transfusions given, a confusing pattern was found. Patients receiving 1 4 units had an unadjusted survival rate similar to that of non-transfused patients.
Non -transfused
o0
P = 0.10
10 years w
5
Fig. 3. Unadjusted recurrence-free survival rates in 268 transfused and in 47 non-transfused patients.
Patients receiving 5-10 units had a poorer prognosis, but patients receiving more than 10units had a prognosis comparable to that of the nontransfused (Fig. 4). Cox multiple regression analysis of the colon cancer-specific survival showed that statistically significant variables were Dukes classification and tumor localization, whereas the other factors,
Recurrence-free survival
A
o/o
1o
IZL
Colon cancer specific survival
o h
]
n\-
transfused
0
>. l o
1 -5
Tra n sf used
50
-
P = 0.10
-I 0
0
0
5
5
10 years
Fig. 2. Unadjusted colon cancer-specific survival rates in 268 transfused and in 47 non-transfused patients.
L
B
5
-
1
0
10 years
Fig. 4. Unadjusted recurrence-free survival rates in 47 non-transfused patients and in 268 transfused, by number of transfusions. 172 patients received 1-5 units, 72 patients received 6 1 0 units. and 19 patients received more than 10 units.
440
E . B . Jakobsen et al.
Table V. Result of Cox multiple regression analysis of colon cancer-specificsurvival Regression coefficient
SD
0.0077 0.208 0.0034 -0.0076
0.225 0.203 0.009 0.083
0.034 1.02 0.38 0.092
-1.919 -1.029
0.445 0.207
4.31 4.97
0.372 0.292 0.272 0.002 0.342
1.06 0.35 2.01 1.00 0.96
Downloaded by [RMIT University Library] at 20:38 08 April 2016
Center Sex Age Hemoglobin level Dukes A versus C B versus C Localization Cecum versus ATD* Sigmoid versus ATD* Rectum versus ATD* Duration of operation Transfusion
0.393 0.102 0.546 0.002 0.327
2
P 0.97 0.31 0.70 0.93 0.00002
