The Effect of Parietal Cell Vagotomy and Selective Vagotomy with Pyloroplasty on Iron Absorption A Prospective Randomized Study B. MAGNUSSON, A. FAXEN, A. CEDERBLAD, L. ROSANDER. J. KEWENTER & L. HALLBERG Dept. of Medicine 11, Dept. of Surgery 111, and Dept. of Radiation Physics. Sahlgren’s Hospital. University of Gothenburg, Gothenburg. Sweden
Scand J Gastroenterol Downloaded from informahealthcare.com by McMaster University on 01/09/15 For personal use only.
Magnusson. B., Faxen. A.. Cederblad, A,,Rosander. L., Kewenter, J. & Hallberg, L. The effect of parietal cell vagotomy and selective vagotomy with pyloroplasty on iron absorption. A prospective randomized study. Scund. J . Gustroent. 1979, 1 4 , 177- 182. Iron absorption from a composite meal was studied in 37 male patients before and 1 year after parietal cell vagotomy (PCV) and selective vagotomy with pyloroplasty (SV + P ) in a prospective randomized series. The ability to absorb dietary non-haem iron was studied by relating in each subject the food iron absorption to the absorption from a small dose of ferrous iron. which has been shown to be unaffected by gastric surgery. After both PCV and SV + P there was a malabsorption of food iron which was statistically significant in patients with increased iron requirements caused by phlebotomy. Malabsorption of food iron was less marked after PCV and SV + P than in patients after gastric resection, and it is concluded that there may be no need for a general prophylactic iron supplementation in patients operated on with PCV and SV + P.
Key-words: Absorption: pyloroplasty; stomach: vagotomy B. Magnusson. M.D., Med. klin. II, Sahlgrenska sjukhuset, S-413 45 Gothenburg, Sweden
Iron deficiency is common after gastric resection (5, 13, 14). Anaemia has also been reported to be common after truncal vagotomy and drainage ( 1 1). Iron deficiency is usually a late sequela of gastric surgery, which means that it takes several years of negative iron balance until a state of iron deficiency can be detected (20). This fact also implies that it takes a very long time to evaluate how new methods of gastric surgery affect iron balance and to estimate the probability that iron deficiency will develop. The most probable cause of iron deficiency after gastric surgery is a malabsorption of food iron. This view is mainly reached by a process of exclusion. since it has not been possible to measure the absorption of iron from composite meals. Recently, however, such a method has been developed (3). The method is based on a uniform labeiling of the nonhaem iron in a meal by an extrinsic radioiron tracer, and a comparison of the absorption of iron from this meal with that of an inorganic reference iron dose given on another day with the subject in a fasting state as an index of the iron status or actually of the
individual ability to absorb iron. It has recently been shown that this method can be used also in patients who have had gastric surgery, since the absorption of the inorganic reference dose is unaffected by the operation (15, 16). By using a standardized meal, comparisons can thus be made between normal subjects and subjects who have had gastric surgery. The aim of this investigation was to study iron absorption in patients operated on with parietal cell vagotomy (PCV) and selective vagotomy with pyloroplasty (SV + P) in a prospective randomized series.
METHOD Iron absorption tests Food iron absorption was measured from a standardized composite meal consisting of hamburgers ( 1 10 g), haricots verts (60 g), and mashed potatoes (150 g). The composition of the meal is described elsewhere (14). Radioiron (1-2 pCi 59Fe) was added dropwise to the three foods. The amount of
Scand J Gastroenterol Downloaded from informahealthcare.com by McMaster University on 01/09/15 For personal use only.
178
B. Magnusson, A . Faxin, A. Cederblad, L . Rosander, J . Kewenter & L . Hallberg
radioiron added was related to the iron content of the foods in order to obtain a fairly homogeneous specific activity in the meal. The meal was served with 150 ml of water. Iron absorption from an inorganic iron salt (reference dose) was measured from a solution of 10 ml 0.0 1 M hydrochloric acid containing 3.0 mg of iron as ferrous sulphate and 30 mg of ascorbic acid. The iron solution contained 2 pCi 55Feand was served in 10-ml vials which were rinsed with water which was also consumed. The meal or the iron salt solution was consumed after an overnight fast on alternate days during 4 consecutive days. Two weeks later the non-haem food iron absorption ("Fe) was measured in a whole body counter (1, 17). The relative absorption of 55Feand 59Fewas calculated from the radioactivities in the food or drink consumed and in blood drawn 2 weeks later. The total absorption of 55Fewas calculated from the relative absorption of 55Feand 59Fe and the total absorption of 59Femeasured in the whole body counter. The activity of 55Feand 59Fein blood samples, in aliquots of the food served, and in the ferrous sulphate solution was determined according to a modification of the method described by Eakins & Brown (7). Pentagastrin-stimulated acid secretion was measured in all patients after an injection of 0.6 g pentagastrin/kg body weight (Peptavlon, 0.25 mg/ml ICI).
Patients Thirty-seven male patients between 23 and 58 years of age were included in the study. They took
part in a consecutive randomized trial of PCV and SV + P in the treatment of duodenal ulcer. In this trial of PCV and SV + P there were 40 men, 3 of whom, however, were not willing to participate in the iron absorption study. The randomization and the surgical technique are described elsewhere (8). None of the patients had had any bleeding Qr any iron therapy during the 2 months prior to the absorption tests. All patients were apparently healthy apart from their duodenal ulcer and had no haemotological abnormalities (Table I). Of the total 37 patients, 16 in the PCV group and 16 in the SV + P group were investigated before and I year after surgery.
Iron absorption study after a phlebotomy
Food iron absorption was also studied in three patients in each post-operative group who were reinvestigated 1 year after surgery following a phlebotomy of 450 ml blood. Five further patients in the randomized trial who had not had any preoperative absorption test were investigated after a similar phlebotomy 1 year postoperatively.
Expression of results As will be discussed later, the probability of detecting malabsorption of food iron is considered to be higher in subjects with high iron requirements. reflected by a high absorption from the reference dose (10). Therefore, absorption data for patients whose absorption from the reference dose exceeded 30% were studied separately.
Table I. Haematological data and acid secretion before and 1 year after parietal cell vagotomy (PCV) and selective vagotomy with pyloroplasty (SV + P) (mean k S.E.M.) Patients and number PCV preop. n = 16
Serum iron, pmol/l
TIBC,
d1
MCHC, g/I erythrocytes
Transferrin saturation,
pmol/l
%
Gastric acid, mmol/30 min
14.6 f 0.3
33.3 rt: 0.2
19.1 k 1.7
60.3 k 2.3
32.9 rt: 3.6
16.6 k 1.8
14.8 f 0.2
33.2 rt: 0.2
26.3 k 5.0
62.4 k 3.7
40.5 k 4.4
10.3 k 1.1
14.7rt: 0.3
33.2 rt: 0.3
17.8 k 1.7
65.1 k 3.8
28.6 & 3.1
16.9 -t 1.2
14.8+ 0.2
32.8 rt: 0.3
25.2k 1.8
6 3 . 2 k 2.0
40.7 k 3.3
8 . 2 f 1.1
HC,
pcv postop. n=21 SV + P preop. n = 16 sv + P postop n = 22
Effect of Vagotomy on Iron Absorption
SV + P group (1 1.8% and 10.8%, respectively). This was also true of the postoperative values (6.8% and 6.4%, respectively). The decrease in food iron absorption after surgery was not statistically significant in either of the groups. The above figures only include subjects studied both before and after surgery.
Food iron absorption per cent
30-
20-
/. Scand J Gastroenterol Downloaded from informahealthcare.com by McMaster University on 01/09/15 For personal use only.
179
10-
2b
40
$0
sb
160
Absorption reference dose (3mg Fe") per cent
Fig. 1. The relationship between the absorption of nonhaem iron in a compositemeal and ferrous iron before (.) and 1 year after parietal cell vagotomy (A) and selective vagotomy with pyloroplasty (0).
Statistical methods For the calculation of regression lines the method of least squares was used, and for the calculation of significance the Wilcoxon Rank Sum Test was used. RESULTS The haematological data and the results of the pentagastrin tests are shown in Table I. There were no significant differences between the two groups of patients as regards their haematological data. The pentagastrin-stimulated acid secretion was significantly lower after SV + P than after PCV (p < 0.05) (9). Tables I1 and 111and Fig. 1 show the iron absorption data from all tests performed. Before surgery there were no significant differences between the two groups.
Iron absorption from the referenceferrous iron salt There were no significant differences between the pre- and post-operative values in either group, and there was no significant difference between PCV and SV + P as regards iron absorption from the iron salt. Food iron absorption Preoperatively there was no significant difference in mean absorption between the PCV and the
Absorption ratio (food ironlreference iron dose) Preoperatively there was no significant difference between the PCV and SV + P group (0.31% and 0.30%, respectively). Postoperatively these figures were 0.30% and 0.19% in the two groups. The decrease in the PCV group (from 0.3 1% to 0.30%) was not statistically significant, whereas the decrease in the SV + P group (from 0.30% to 0.19%) was significant (p < 0.02). These comparisons only comprise subjects studied both before and after operation. Iron absorption in patients with reference dose absorption exceeding 30% Preoperatively 12 patients had an iron absorption from the iron salt L 30%. Postoperatively this limit was exceeded in 19 tests, 8 following PCV and 11 following SV + P (Tables I1 and 111). Table IV shows the absorption data for these tests. When the preoperative and the postoperative figures are compared, there was no significant decrease in food iron or iron salt absorption. The absorption ratio, however, was significantly decreased both after PCV and after SV + P (p < 0.01). There was no significant difference between the two groups. There was no correlation between iron absorption and the postoperative pentagastrin-stimulated acid secretion. DISCUSSION Anaemia due to iron deficiency has been reported by Baird et al. (2) and Deller & Witt (6) in 25% of patients after partial gastrectomy. Anaemia is less frequent in patients after truncal vagotomy with drainage and patients who have had a gastric resection 15 years earlier ( 1 1). However, anaemia develops later after vagotomy and drainage than after gastric resection (20), and the type of drainage (pyloroplasty or gastroenterostomy) influences the incidence of anaemia (19). There are no reports of
180
B . Magnusson, A . Fawkn,
A. Cederblad, L . Rosander, J. Kewenter & L . Hallberg
Table 11. Iron absorption before and 1 year after parietal cell vagotomy Preoperatively
Postoperatively
Food iron,
Iron sall
Iron salt,
%
%
Abs. ratio * Foodhalt
Food iron,
Subject
%
%
I.D.
27
65
0.40
K.S.
2
13
0.18
K.J.
5
20
0.23
S.N. S.A. G.K.
22 18 38 2 13 1 6 10 2 26 9 4 4
72 86 86 22 47 8 8 19 15 72 26 14 17
0.29 0.20 0.42 0.08 0.26 0.14 0.77 0.53 0.13 0.36 0.34 0.3 1 0.22
9 6t 7 9t 7 19t 8 10 8 3 9 2 3 4 4 9 9 9 8
14 25t 16 42t 19 66t 33 37 25 16 52 13 8 7 22 24 56 82 32 24$
0.65 0.26t 0.45 0.21t 0.39 0.29t 0.25 0.27 0.30 0.19 0. I 8 0.18 0.37 0.5 1 0.16 0.35 0.15 0.12 0.24 0.25$ 0.37$
11.8 11.2
36.9 29.2
0.3 1 0.17
30.0 19.8
0.29 0.13
Abs. ratio * Foodha1t
Scand J Gastroenterol Downloaded from informahealthcare.com by McMaster University on 01/09/15 For personal use only.
~
C.L. S.L.
H.B. E.K. N.T. R.N. S.J. F.A. A.H. N.R. K.G.J. K.A. Mean S.D.
a 6$
7.4 3.6
* Data calculated from blood samples. t Reinvestigation after a phlebotomy of 450 ml blood. $ Investigation after a phlebotomy of 450 ml blood. anaemia after selective vagotomy with or without drainage. Since anaemia is a late sequela of gastric surgery, there are still no reports of the haematological effects of the recently introduced PCV, where the antrum pylorus region is left innervated and no drainage operation is necessary ( 12). ‘Postresectional anaemia’ is mainly due to iron deficiency ( 13), and the most probable cause for this is a malabsorption of food iron ( 15), although alternative explanations have been suggested ( 18). The iron absorption of an individual is influenced by the iron status, for example, the size of the iron stores, and by temporary changes in the iron balance caused by, for example, bleeding. To decide whether the iron absorption has changed because of gastric surgery, it is therefore not enough to measure the absorption of food iron before and after surgery, since the iron status of the individual can have
changed after surgery because of, for example, bleeding or iron therapy. The food iron absorption in each individual must therefore always be related to his iron status at the time of investigation (14). Iron absorption from an inorganic iron salt in unoperated subjects is dependent mainly on the iron status, and it was recently shown that even in patients after gastric surgery the absorption from an iron salt could be used as an index of the iron status and thus serve as a basis for comparison. Thus, by measuring the iron absorption from a composite meal and from a reference dose on alternate days, food iron absorption can accurately be measured in patients who have had gastric operations ( 15), and a malabsorption of food iron can be detected and its severity estimated long before any haematological or biochemical manifestations have developed. The absorption from the iron salt (reference dose)
Effect of Vagolomy on Iron Absorption
181
Table 111. Iron absorption before and 1 year after selective vagotomy with pyloroplasty Postoperatively
Preoperative1y %
Iron salt, %
Abs. ratio * FoodJsalt
Food iron, %
Iron salt,
Subject S.E. K.E.E. H.G. E.O. J.H.
16 31 3 4 4
33 80 21 31 22
0.48 0.37 0.14 0.13 0.18
5 4
B.Q. R.K. 1.0.
2 I 10
8 14 31
0.26 0.50 0.33
A.A. S.D.
26 6
65 23
0.39 0.24
L.O. B.J.
4 2 3
17 9 20
0.24 0.18 0. I4
S.J. L.O. L.P. S.B. Y .A. R.J.
9
15
-
18
0.52
35
91
0.37
8 4t 3 I 10 6t 15 2 5t 6 6 2 15 11 1I$ 1$ 9$ 7
31 22 22 37 28 36t 12 37 33 26t 78 12 13t 34 29 10 68 53 33$ 5$ 2% 49
0.16 0. I8 0.04 0.03 0.30 0.12t 0.24 0.19 0.29 0.23t 0.19 0.2 1 0.35t 0.17 0. I9 0.18 0.24 0.2 1 0.33$ 0.22 0.3Z 0.15
Mean ? S.D.
10.8 11.0
31.5 26.1
0.30 0.16
6.3 4.2
3 1.7 18.1
0.2 1 0.13
Scand J Gastroenterol Downloaded from informahealthcare.com by McMaster University on 01/09/15 For personal use only.
Food iron,
K.S.
1 1
YO
Abs. ratio" Foodhalt
-
* Data calculated from blood samples. t Reinvestigation after a phlebotomy of 450 ml blood. $ Investigation after a phlebotomy of 450 ml blood.
in the present study did not significantly change after surgery, which meant that there were no significant changes in the iron status. None of the patients had had any bleeding during the postoperative year, and therefore no changes in the iron status were to be expected. Nor were there any significant changes of the percentage food iron absorption after surgery. However, the absorption ratio (food iron/iron salt) was significantly decreased after SV + P (p < 0.02), which means that when the food iron absorption is related to the absorption from the reference dose, a malabsorption could be detected. There was no decrease in the absorption ratio after PCV (p > 0.10). A more sensitive test to detect a malabsorption of iron is probably to study the absorption of iron in iron-deficient patients and in patients with negative
iron balance, such as after bleeding. This was the reason why iron absorption was studied in 1 1 of the operated patients 1 to 2 weeks after a phlebotomy of 450 ml blood. An iron absorption of more than 40% from the reference dose usually indicates iron deficiency or a more significant negative iron balance (4), but in previous studies 30% absorption has been used as an arbitrary indicator for iron deficiency (10). In spite of the phlebotomy all patients did not reach high absorption values (Tables I1 and 111). Factors such as too short an interval between the phlebotomy and the absorption study may explain why an increased iron absorption was not observed in all these patients. Absorption values from the reference dose exceeding 30% were found in 12 patients before operation and in 8 after PCV and 11 after SV + P. When
182
B. Magnusson, A. Faxin, A. Cederblad, L. Rosander, J. Kewenter & L. Hallberg
Table IV. Absorption data in patients with an iron absorption 30% from the iron salt. Mean Postoperatively *
Preoperatively PCV, n
n =I2
Scand J Gastroenterol Downloaded from informahealthcare.com by McMaster University on 01/09/15 For personal use only.
+- S.D. (median)
SV + P, n
=8
Food iron, %
Iron salt, %
Abs. ratio Foodhalt
Food iron, %
Iron salt, %
Abs. ratio Foodlsalt
Food iron,
22.2 & 10.3 (24.0)
63.8 k23.1 (68.5)
0.33 kO.10
10.1 k3.6 (9.0)
50.0 t17.6 (47.0)
0.2 1 k0.06 (0.23)
8.4 f4.5 (7.0)
(0.36)
* PCV = parietal cell vagotomy;
SV
+ P = selective vagotomy
%
=
11
Iron salt, %
Abs. ratio Foodlsalt
44.5
0.19 kO.08 (0.19)
k 15.8
(37.0)
with pyloroplasty.
the absorption ratios for these preoperative patients REFERENCES 1. Arvidsson, B.. Skoldborn. H. & Isaksson, B. The third were compared with those found postoperatively, a International Conference on Medical Physics, includmalabsorption of food iron was found both after ing Medical Engineering. Chalmers University of PVC and after SV + P (p < 0.01) (Table IV). Technology. Abstr. 41. p. 41. Gothenburg. Sweden. 1972 The cause of the malabsorption of food iron was 2. Baird, I. M., Blackburn. E. K. & Wilson. G. M. Quart. not investigated in this study. It should be menJ . Med. 1959. 28, 21-34 tioned, however; that there was no correlation be3. Bjorn-Rasmussen, E., Hallberg. L.. Magnusson. B., Rossander, L., Svanberg. B. & Arvidson. B. Amer. J . tween food iron absorption and postoperative gasClin. Nutr. 1976, 29. 772-778 tric acid secretion. 4. Bjorn-Rasmussen, E.. Hallberg. L.. Magnusson. B. & In a previous study in which exactly the same Rossander. L. To be published 5. Brookes, V. S., Meynell. M. J.. Bold. A. M. & Kingstechnique was used in the same laboratory in ton. R. D. Brit. J. Surg. 1974, 61. 9-15 patients operated on with a Billroth I and Billroth I1 6. Deller. D. J. & Witt. L. J. Quart. J . Med. 1962. 31. partial gastrectomy, the absorption ratios were 0.13 7 1-88 7. Eakins, J . D. & Brown, D. A. Znt. J . Appl. Radial. and 0.06, respectively ( 15). These figures are signif1966, 17, 391-397 icantly lower than those found after PCV and 8. Faxen. A. & Kewenter. J. Scand. J . Gasfroent. In SV + P (p < 0.0 1). Thus the malabsorption of food press. 1978 9. Faxin. A. & Kewenter. J. Scand. J. Gastroent. In iron after PCV and SV + P is significantly less than press. 1978 after partial gastrectomy. 10. Hallberg. L., Bjorn-Rasmussen. E.. Rossander. L. & It may thus be concluded that PCV and SV + P Suwanik. R. Amer. J. Clin. Nutr. 1977.30,539-548 both lead to a malabsorption of food iron. However, 11. Johnson, H. D., Khan, T. A.. Srivatsa. R.. Doyle, F. H. & Welbourn. R. B. Brit. J. Surg. 1969. 56. 4-9 this malabsorption is milder than that after gastric 12. Johnston, D. & Wilkinson. A. R. Brit. J . Surg. 1970. resection. Whether an iron deficiency will develop in 57. 289-296 patients after PCV and SV + P depends on several 13. Lloyd, P. & Valberg, L. S. Amer. J. Dig. Dis. 1977. 22. 598-604 factors, such as the iron stores at operation and the 14. Magnusson, B. Scand. J. Haematol. 1976, Suppl. 26, iron intake. The results of the present study indicate 7-16 that there may be no need for a general prophylactic 15. Magnusson, B.. Hallberg, L. & Arvidsson, B. Scand. J . Haematol. 1976, Suppl. 26. 69-86 iron supplementation in patients after PCV and 16. Magnusson, B.. Solvell. L. & Rehnberg. 0. Scand. J . sv + P. Haematol. 1976. Suppl. 26. 53-68 ACKNOWLEDGEMENT This study was supported by the Swedish Medical Research Council (project No. B78- 19X-0472 103A) and Goteborgs Lakaresallskap. Received 28 June 1978 Accepted 20 September 1978
17. Skoldborn, H., Arvidsson, B. & Andersson. M. Acta Radiol. 1972, Suppl. 3 13. 233-24 1 18. Toskes, P. P. Major Probl. Clin. Surg. 1976, 20, 119-128 19. Wastell, C. Ann. Roy. Coll. Surg. Engl. 1969. 45. 193-21 1 20. Wheldon. E. J., Venables. C. W. &Johnston. I. D. A. Lancet 1970. 1. 437-440
Scand J Gastroenterol Downloaded from informahealthcare.com by McMaster University on 01/09/15 For personal use only.
Magnusson. B., Faxen. A.. Cederblad, A,,Rosander. L., Kewenter, J. & Hallberg, L. The effect of parietal cell vagotomy and selective vagotomy with pyloroplasty on iron absorption. A prospective randomized study. Scund. J . Gustroent. 1979, 1 4 , 177- 182. Iron absorption from a composite meal was studied in 37 male patients before and 1 year after parietal cell vagotomy (PCV) and selective vagotomy with pyloroplasty (SV + P ) in a prospective randomized series. The ability to absorb dietary non-haem iron was studied by relating in each subject the food iron absorption to the absorption from a small dose of ferrous iron. which has been shown to be unaffected by gastric surgery. After both PCV and SV + P there was a malabsorption of food iron which was statistically significant in patients with increased iron requirements caused by phlebotomy. Malabsorption of food iron was less marked after PCV and SV + P than in patients after gastric resection, and it is concluded that there may be no need for a general prophylactic iron supplementation in patients operated on with PCV and SV + P.
Key-words: Absorption: pyloroplasty; stomach: vagotomy B. Magnusson. M.D., Med. klin. II, Sahlgrenska sjukhuset, S-413 45 Gothenburg, Sweden
Iron deficiency is common after gastric resection (5, 13, 14). Anaemia has also been reported to be common after truncal vagotomy and drainage ( 1 1). Iron deficiency is usually a late sequela of gastric surgery, which means that it takes several years of negative iron balance until a state of iron deficiency can be detected (20). This fact also implies that it takes a very long time to evaluate how new methods of gastric surgery affect iron balance and to estimate the probability that iron deficiency will develop. The most probable cause of iron deficiency after gastric surgery is a malabsorption of food iron. This view is mainly reached by a process of exclusion. since it has not been possible to measure the absorption of iron from composite meals. Recently, however, such a method has been developed (3). The method is based on a uniform labeiling of the nonhaem iron in a meal by an extrinsic radioiron tracer, and a comparison of the absorption of iron from this meal with that of an inorganic reference iron dose given on another day with the subject in a fasting state as an index of the iron status or actually of the
individual ability to absorb iron. It has recently been shown that this method can be used also in patients who have had gastric surgery, since the absorption of the inorganic reference dose is unaffected by the operation (15, 16). By using a standardized meal, comparisons can thus be made between normal subjects and subjects who have had gastric surgery. The aim of this investigation was to study iron absorption in patients operated on with parietal cell vagotomy (PCV) and selective vagotomy with pyloroplasty (SV + P) in a prospective randomized series.
METHOD Iron absorption tests Food iron absorption was measured from a standardized composite meal consisting of hamburgers ( 1 10 g), haricots verts (60 g), and mashed potatoes (150 g). The composition of the meal is described elsewhere (14). Radioiron (1-2 pCi 59Fe) was added dropwise to the three foods. The amount of
Scand J Gastroenterol Downloaded from informahealthcare.com by McMaster University on 01/09/15 For personal use only.
178
B. Magnusson, A . Faxin, A. Cederblad, L . Rosander, J . Kewenter & L . Hallberg
radioiron added was related to the iron content of the foods in order to obtain a fairly homogeneous specific activity in the meal. The meal was served with 150 ml of water. Iron absorption from an inorganic iron salt (reference dose) was measured from a solution of 10 ml 0.0 1 M hydrochloric acid containing 3.0 mg of iron as ferrous sulphate and 30 mg of ascorbic acid. The iron solution contained 2 pCi 55Feand was served in 10-ml vials which were rinsed with water which was also consumed. The meal or the iron salt solution was consumed after an overnight fast on alternate days during 4 consecutive days. Two weeks later the non-haem food iron absorption ("Fe) was measured in a whole body counter (1, 17). The relative absorption of 55Feand 59Fewas calculated from the radioactivities in the food or drink consumed and in blood drawn 2 weeks later. The total absorption of 55Fewas calculated from the relative absorption of 55Feand 59Fe and the total absorption of 59Femeasured in the whole body counter. The activity of 55Feand 59Fein blood samples, in aliquots of the food served, and in the ferrous sulphate solution was determined according to a modification of the method described by Eakins & Brown (7). Pentagastrin-stimulated acid secretion was measured in all patients after an injection of 0.6 g pentagastrin/kg body weight (Peptavlon, 0.25 mg/ml ICI).
Patients Thirty-seven male patients between 23 and 58 years of age were included in the study. They took
part in a consecutive randomized trial of PCV and SV + P in the treatment of duodenal ulcer. In this trial of PCV and SV + P there were 40 men, 3 of whom, however, were not willing to participate in the iron absorption study. The randomization and the surgical technique are described elsewhere (8). None of the patients had had any bleeding Qr any iron therapy during the 2 months prior to the absorption tests. All patients were apparently healthy apart from their duodenal ulcer and had no haemotological abnormalities (Table I). Of the total 37 patients, 16 in the PCV group and 16 in the SV + P group were investigated before and I year after surgery.
Iron absorption study after a phlebotomy
Food iron absorption was also studied in three patients in each post-operative group who were reinvestigated 1 year after surgery following a phlebotomy of 450 ml blood. Five further patients in the randomized trial who had not had any preoperative absorption test were investigated after a similar phlebotomy 1 year postoperatively.
Expression of results As will be discussed later, the probability of detecting malabsorption of food iron is considered to be higher in subjects with high iron requirements. reflected by a high absorption from the reference dose (10). Therefore, absorption data for patients whose absorption from the reference dose exceeded 30% were studied separately.
Table I. Haematological data and acid secretion before and 1 year after parietal cell vagotomy (PCV) and selective vagotomy with pyloroplasty (SV + P) (mean k S.E.M.) Patients and number PCV preop. n = 16
Serum iron, pmol/l
TIBC,
d1
MCHC, g/I erythrocytes
Transferrin saturation,
pmol/l
%
Gastric acid, mmol/30 min
14.6 f 0.3
33.3 rt: 0.2
19.1 k 1.7
60.3 k 2.3
32.9 rt: 3.6
16.6 k 1.8
14.8 f 0.2
33.2 rt: 0.2
26.3 k 5.0
62.4 k 3.7
40.5 k 4.4
10.3 k 1.1
14.7rt: 0.3
33.2 rt: 0.3
17.8 k 1.7
65.1 k 3.8
28.6 & 3.1
16.9 -t 1.2
14.8+ 0.2
32.8 rt: 0.3
25.2k 1.8
6 3 . 2 k 2.0
40.7 k 3.3
8 . 2 f 1.1
HC,
pcv postop. n=21 SV + P preop. n = 16 sv + P postop n = 22
Effect of Vagotomy on Iron Absorption
SV + P group (1 1.8% and 10.8%, respectively). This was also true of the postoperative values (6.8% and 6.4%, respectively). The decrease in food iron absorption after surgery was not statistically significant in either of the groups. The above figures only include subjects studied both before and after surgery.
Food iron absorption per cent
30-
20-
/. Scand J Gastroenterol Downloaded from informahealthcare.com by McMaster University on 01/09/15 For personal use only.
179
10-
2b
40
$0
sb
160
Absorption reference dose (3mg Fe") per cent
Fig. 1. The relationship between the absorption of nonhaem iron in a compositemeal and ferrous iron before (.) and 1 year after parietal cell vagotomy (A) and selective vagotomy with pyloroplasty (0).
Statistical methods For the calculation of regression lines the method of least squares was used, and for the calculation of significance the Wilcoxon Rank Sum Test was used. RESULTS The haematological data and the results of the pentagastrin tests are shown in Table I. There were no significant differences between the two groups of patients as regards their haematological data. The pentagastrin-stimulated acid secretion was significantly lower after SV + P than after PCV (p < 0.05) (9). Tables I1 and 111and Fig. 1 show the iron absorption data from all tests performed. Before surgery there were no significant differences between the two groups.
Iron absorption from the referenceferrous iron salt There were no significant differences between the pre- and post-operative values in either group, and there was no significant difference between PCV and SV + P as regards iron absorption from the iron salt. Food iron absorption Preoperatively there was no significant difference in mean absorption between the PCV and the
Absorption ratio (food ironlreference iron dose) Preoperatively there was no significant difference between the PCV and SV + P group (0.31% and 0.30%, respectively). Postoperatively these figures were 0.30% and 0.19% in the two groups. The decrease in the PCV group (from 0.3 1% to 0.30%) was not statistically significant, whereas the decrease in the SV + P group (from 0.30% to 0.19%) was significant (p < 0.02). These comparisons only comprise subjects studied both before and after operation. Iron absorption in patients with reference dose absorption exceeding 30% Preoperatively 12 patients had an iron absorption from the iron salt L 30%. Postoperatively this limit was exceeded in 19 tests, 8 following PCV and 11 following SV + P (Tables I1 and 111). Table IV shows the absorption data for these tests. When the preoperative and the postoperative figures are compared, there was no significant decrease in food iron or iron salt absorption. The absorption ratio, however, was significantly decreased both after PCV and after SV + P (p < 0.01). There was no significant difference between the two groups. There was no correlation between iron absorption and the postoperative pentagastrin-stimulated acid secretion. DISCUSSION Anaemia due to iron deficiency has been reported by Baird et al. (2) and Deller & Witt (6) in 25% of patients after partial gastrectomy. Anaemia is less frequent in patients after truncal vagotomy with drainage and patients who have had a gastric resection 15 years earlier ( 1 1). However, anaemia develops later after vagotomy and drainage than after gastric resection (20), and the type of drainage (pyloroplasty or gastroenterostomy) influences the incidence of anaemia (19). There are no reports of
180
B . Magnusson, A . Fawkn,
A. Cederblad, L . Rosander, J. Kewenter & L . Hallberg
Table 11. Iron absorption before and 1 year after parietal cell vagotomy Preoperatively
Postoperatively
Food iron,
Iron sall
Iron salt,
%
%
Abs. ratio * Foodhalt
Food iron,
Subject
%
%
I.D.
27
65
0.40
K.S.
2
13
0.18
K.J.
5
20
0.23
S.N. S.A. G.K.
22 18 38 2 13 1 6 10 2 26 9 4 4
72 86 86 22 47 8 8 19 15 72 26 14 17
0.29 0.20 0.42 0.08 0.26 0.14 0.77 0.53 0.13 0.36 0.34 0.3 1 0.22
9 6t 7 9t 7 19t 8 10 8 3 9 2 3 4 4 9 9 9 8
14 25t 16 42t 19 66t 33 37 25 16 52 13 8 7 22 24 56 82 32 24$
0.65 0.26t 0.45 0.21t 0.39 0.29t 0.25 0.27 0.30 0.19 0. I 8 0.18 0.37 0.5 1 0.16 0.35 0.15 0.12 0.24 0.25$ 0.37$
11.8 11.2
36.9 29.2
0.3 1 0.17
30.0 19.8
0.29 0.13
Abs. ratio * Foodha1t
Scand J Gastroenterol Downloaded from informahealthcare.com by McMaster University on 01/09/15 For personal use only.
~
C.L. S.L.
H.B. E.K. N.T. R.N. S.J. F.A. A.H. N.R. K.G.J. K.A. Mean S.D.
a 6$
7.4 3.6
* Data calculated from blood samples. t Reinvestigation after a phlebotomy of 450 ml blood. $ Investigation after a phlebotomy of 450 ml blood. anaemia after selective vagotomy with or without drainage. Since anaemia is a late sequela of gastric surgery, there are still no reports of the haematological effects of the recently introduced PCV, where the antrum pylorus region is left innervated and no drainage operation is necessary ( 12). ‘Postresectional anaemia’ is mainly due to iron deficiency ( 13), and the most probable cause for this is a malabsorption of food iron ( 15), although alternative explanations have been suggested ( 18). The iron absorption of an individual is influenced by the iron status, for example, the size of the iron stores, and by temporary changes in the iron balance caused by, for example, bleeding. To decide whether the iron absorption has changed because of gastric surgery, it is therefore not enough to measure the absorption of food iron before and after surgery, since the iron status of the individual can have
changed after surgery because of, for example, bleeding or iron therapy. The food iron absorption in each individual must therefore always be related to his iron status at the time of investigation (14). Iron absorption from an inorganic iron salt in unoperated subjects is dependent mainly on the iron status, and it was recently shown that even in patients after gastric surgery the absorption from an iron salt could be used as an index of the iron status and thus serve as a basis for comparison. Thus, by measuring the iron absorption from a composite meal and from a reference dose on alternate days, food iron absorption can accurately be measured in patients who have had gastric operations ( 15), and a malabsorption of food iron can be detected and its severity estimated long before any haematological or biochemical manifestations have developed. The absorption from the iron salt (reference dose)
Effect of Vagolomy on Iron Absorption
181
Table 111. Iron absorption before and 1 year after selective vagotomy with pyloroplasty Postoperatively
Preoperative1y %
Iron salt, %
Abs. ratio * FoodJsalt
Food iron, %
Iron salt,
Subject S.E. K.E.E. H.G. E.O. J.H.
16 31 3 4 4
33 80 21 31 22
0.48 0.37 0.14 0.13 0.18
5 4
B.Q. R.K. 1.0.
2 I 10
8 14 31
0.26 0.50 0.33
A.A. S.D.
26 6
65 23
0.39 0.24
L.O. B.J.
4 2 3
17 9 20
0.24 0.18 0. I4
S.J. L.O. L.P. S.B. Y .A. R.J.
9
15
-
18
0.52
35
91
0.37
8 4t 3 I 10 6t 15 2 5t 6 6 2 15 11 1I$ 1$ 9$ 7
31 22 22 37 28 36t 12 37 33 26t 78 12 13t 34 29 10 68 53 33$ 5$ 2% 49
0.16 0. I8 0.04 0.03 0.30 0.12t 0.24 0.19 0.29 0.23t 0.19 0.2 1 0.35t 0.17 0. I9 0.18 0.24 0.2 1 0.33$ 0.22 0.3Z 0.15
Mean ? S.D.
10.8 11.0
31.5 26.1
0.30 0.16
6.3 4.2
3 1.7 18.1
0.2 1 0.13
Scand J Gastroenterol Downloaded from informahealthcare.com by McMaster University on 01/09/15 For personal use only.
Food iron,
K.S.
1 1
YO
Abs. ratio" Foodhalt
-
* Data calculated from blood samples. t Reinvestigation after a phlebotomy of 450 ml blood. $ Investigation after a phlebotomy of 450 ml blood.
in the present study did not significantly change after surgery, which meant that there were no significant changes in the iron status. None of the patients had had any bleeding during the postoperative year, and therefore no changes in the iron status were to be expected. Nor were there any significant changes of the percentage food iron absorption after surgery. However, the absorption ratio (food iron/iron salt) was significantly decreased after SV + P (p < 0.02), which means that when the food iron absorption is related to the absorption from the reference dose, a malabsorption could be detected. There was no decrease in the absorption ratio after PCV (p > 0.10). A more sensitive test to detect a malabsorption of iron is probably to study the absorption of iron in iron-deficient patients and in patients with negative
iron balance, such as after bleeding. This was the reason why iron absorption was studied in 1 1 of the operated patients 1 to 2 weeks after a phlebotomy of 450 ml blood. An iron absorption of more than 40% from the reference dose usually indicates iron deficiency or a more significant negative iron balance (4), but in previous studies 30% absorption has been used as an arbitrary indicator for iron deficiency (10). In spite of the phlebotomy all patients did not reach high absorption values (Tables I1 and 111). Factors such as too short an interval between the phlebotomy and the absorption study may explain why an increased iron absorption was not observed in all these patients. Absorption values from the reference dose exceeding 30% were found in 12 patients before operation and in 8 after PCV and 11 after SV + P. When
182
B. Magnusson, A. Faxin, A. Cederblad, L. Rosander, J. Kewenter & L. Hallberg
Table IV. Absorption data in patients with an iron absorption 30% from the iron salt. Mean Postoperatively *
Preoperatively PCV, n
n =I2
Scand J Gastroenterol Downloaded from informahealthcare.com by McMaster University on 01/09/15 For personal use only.
+- S.D. (median)
SV + P, n
=8
Food iron, %
Iron salt, %
Abs. ratio Foodhalt
Food iron, %
Iron salt, %
Abs. ratio Foodlsalt
Food iron,
22.2 & 10.3 (24.0)
63.8 k23.1 (68.5)
0.33 kO.10
10.1 k3.6 (9.0)
50.0 t17.6 (47.0)
0.2 1 k0.06 (0.23)
8.4 f4.5 (7.0)
(0.36)
* PCV = parietal cell vagotomy;
SV
+ P = selective vagotomy
%
=
11
Iron salt, %
Abs. ratio Foodlsalt
44.5
0.19 kO.08 (0.19)
k 15.8
(37.0)
with pyloroplasty.
the absorption ratios for these preoperative patients REFERENCES 1. Arvidsson, B.. Skoldborn. H. & Isaksson, B. The third were compared with those found postoperatively, a International Conference on Medical Physics, includmalabsorption of food iron was found both after ing Medical Engineering. Chalmers University of PVC and after SV + P (p < 0.01) (Table IV). Technology. Abstr. 41. p. 41. Gothenburg. Sweden. 1972 The cause of the malabsorption of food iron was 2. Baird, I. M., Blackburn. E. K. & Wilson. G. M. Quart. not investigated in this study. It should be menJ . Med. 1959. 28, 21-34 tioned, however; that there was no correlation be3. Bjorn-Rasmussen, E., Hallberg. L.. Magnusson. B., Rossander, L., Svanberg. B. & Arvidson. B. Amer. J . tween food iron absorption and postoperative gasClin. Nutr. 1976, 29. 772-778 tric acid secretion. 4. Bjorn-Rasmussen, E.. Hallberg. L.. Magnusson. B. & In a previous study in which exactly the same Rossander. L. To be published 5. Brookes, V. S., Meynell. M. J.. Bold. A. M. & Kingstechnique was used in the same laboratory in ton. R. D. Brit. J. Surg. 1974, 61. 9-15 patients operated on with a Billroth I and Billroth I1 6. Deller. D. J. & Witt. L. J. Quart. J . Med. 1962. 31. partial gastrectomy, the absorption ratios were 0.13 7 1-88 7. Eakins, J . D. & Brown, D. A. Znt. J . Appl. Radial. and 0.06, respectively ( 15). These figures are signif1966, 17, 391-397 icantly lower than those found after PCV and 8. Faxen. A. & Kewenter. J. Scand. J . Gasfroent. In SV + P (p < 0.0 1). Thus the malabsorption of food press. 1978 9. Faxin. A. & Kewenter. J. Scand. J. Gastroent. In iron after PCV and SV + P is significantly less than press. 1978 after partial gastrectomy. 10. Hallberg. L., Bjorn-Rasmussen. E.. Rossander. L. & It may thus be concluded that PCV and SV + P Suwanik. R. Amer. J. Clin. Nutr. 1977.30,539-548 both lead to a malabsorption of food iron. However, 11. Johnson, H. D., Khan, T. A.. Srivatsa. R.. Doyle, F. H. & Welbourn. R. B. Brit. J. Surg. 1969. 56. 4-9 this malabsorption is milder than that after gastric 12. Johnston, D. & Wilkinson. A. R. Brit. J . Surg. 1970. resection. Whether an iron deficiency will develop in 57. 289-296 patients after PCV and SV + P depends on several 13. Lloyd, P. & Valberg, L. S. Amer. J. Dig. Dis. 1977. 22. 598-604 factors, such as the iron stores at operation and the 14. Magnusson, B. Scand. J. Haematol. 1976, Suppl. 26, iron intake. The results of the present study indicate 7-16 that there may be no need for a general prophylactic 15. Magnusson, B.. Hallberg, L. & Arvidsson, B. Scand. J . Haematol. 1976, Suppl. 26. 69-86 iron supplementation in patients after PCV and 16. Magnusson, B.. Solvell. L. & Rehnberg. 0. Scand. J . sv + P. Haematol. 1976. Suppl. 26. 53-68 ACKNOWLEDGEMENT This study was supported by the Swedish Medical Research Council (project No. B78- 19X-0472 103A) and Goteborgs Lakaresallskap. Received 28 June 1978 Accepted 20 September 1978
17. Skoldborn, H., Arvidsson, B. & Andersson. M. Acta Radiol. 1972, Suppl. 3 13. 233-24 1 18. Toskes, P. P. Major Probl. Clin. Surg. 1976, 20, 119-128 19. Wastell, C. Ann. Roy. Coll. Surg. Engl. 1969. 45. 193-21 1 20. Wheldon. E. J., Venables. C. W. &Johnston. I. D. A. Lancet 1970. 1. 437-440
