World J. Surg. 2, 91-100, 1978
The Aarhus County Vagotomy Trial I I . A n I n t e r i m R e p o r t on R e d u c t i o n in A c i d S e c r e t i o n a n d U l c e r R e c u r r e n c e R a t e F o l l o w i n g P a r i e t a l Ceil V a g o t o m y a n d Selective G a s t r i c V a g o t o m y Daniel Andersen, M.D., Ph.D., Hans Hr M.D., Ph.D., and Erik Amdrup, M.D., Ph.D. Department of Surgical Gastroenterology, Amtssygehuset and Kommunehospitalet, Aarhus, and Department of Surgery, Centralsygehuset, Randers, University of Aarhus, Denmark
rence was found to be constant from month to month during the first 21/2 years, after which no new recurrent ulcers were observed. It is suggested that for DU, PCV is preferable to SGV + D because the recurrence rate is the same but the incidence of sequelae is lower. When PCV is used for PPU, a higher ulcer recurrence rate may be expected.
In a prospective clinical trial, vagotomy for duodenal ulcer (DU) and prepylorie ulcer (PPU) was performed in 748 patients, 353 of whom were randomly allocated to selective gastric vagotomy and drainage (SGV + D), 54 to SGV + antrectomy (A), 273 to parietal cell vagotomy (PCV), and 68 to PCV + D. By 3 months postoperatively, basal acid secretion (BAO) had not stabilized. During the following year patients with SGV + A showed a decrease, while those with the other operations showed a rise in BAO, significant for SGV + D. One year after operation the level of BAO was the same after the 3 operations that did not remove the antrum. Peak acid output after pentagastrin stimulation (PAOpg) continued to decrease from 3 months to 1 year after SGV + A, while the other operations were followed by an increase, statistically significant for PCV. After 1 year the postoperative reduction in PAO pg was 90% for SGV + A, 45% for PCV, and approximately 60% for SGV + D and PCV + D. Overall clinical grading showed more failures following PCV than after SGV. Since failures after PCV were mainly ulcer recurrences, the final grading (after treatment of the failures) showed an equal number of failures for the 2 operations. Calculation of the probability of ulcer recurrence suggested a 6% rate after SGV + D and an 11% rate after PCV. However, when calculations took into account the location of the primary ulcer, the recurrence rate was the same after SGV + D for DU and PPU, while PCV showed a similar rate when used for DU but an incidence of 22% when used for PPU. The risk of recur-
In p a r t I o f this i n t e r i m r e p o r t [ 1] a c o n t r o l l e d trial was described involving patients with proven duodenal ulcer who were electively treated by parietal cell v a g o t o m y (PCV) w i t h o r w i t h o u t d r a i n a g e (D), a n d s e l e c t i v e gastric v a g o t o m y ( S G V ) w i t h D o r a n t r e c t o m y (A). D e t a i l s w e r e g i v e n o f t h e r a n d o m i zation method, intraoperative and postoperative c o m p l i c a t i o n s , a n d the i n c i d e n c e o f s e q u e l a e as j u d g e d at the 2 - y e a r f o l l o w - u p e x a m i n a t i o n . T h i s communication deals with the results of studies of gastric acid secretion performed 3 months and 1 year p o s t o p e r a t i v e l y , specifically t h e b a s a l a c i d o u t p u t ( B A O ) a n d the p e a k a c i d o u t p u t f o l l o w i n g p e n t a g a s trin s t i m u l a t i o n (PAOPg). F u r t h e r m o r e , o b s e r v a t i o n s a r e r e p o r t e d o n the u l c e r r e c u r r e n c e r a t e a f t e r 2 y e a r s o f f o l l o w - u p , a n d the i n t e g r a t e d r e c u r r e n c e r a t e for t h e t o t a l p a t i e n t m a t e r i a l d u r i n g t h e o b s e r v a tion y e a r s 1972-1977.
Aided by grant no. S L F 512-5456 from the Danish Medical Research Council. Reprint requests: Erik Amdrup, M.D., Ph.D., Surgical Gastroenterological Dpt. L, Kommunehospitalet, 8000 Aarhus C., Denmark.
0364-2313/78/0002-0091 $02.00 9 1978 Societ6 Internationale de Chirurgie
91
92
World J. Surg. Vol. 2, No. 1, January, 1978
Material and Methods
The trial involved 748 patients. According to random allocation, 353 had SGV + D, 54 SGV + A, 68 PCV + D, and 273 PCV without drainage. Five patients died during the early postoperative period. All patients underwent clinical examination 3 months and every year after surgery. A pentagastrin stimulation test was performed preoperatively and was repeated postoperatively at 3 months and 1 year. The fasting contents of the stomach were aspirated during a 15-minute period. BAO was then determined by aspiration during 4 periods of 15 minutes each. Pentagastrin in a dose of 6/xg/kg body weight was given intramuscularly, and the stimulated secretion was followed for 4 periods of 15 minutes each. Postoperatively the dose of pentagastrin was 10 tzg/ kg. Volume of gastric juice was measured and acid concentration was determined by titration to p H 7 with 0.1 N N a O H by an automatic titrator (Radiometer, Copenhagen). PAO pg was calculated from the 2 highest consecutive samples multiplied by 2. The patients who developed dyspeptic s y m p t o m s were investigated by endoscopy and also often had radiologic studies. If ulcer recurrence was found, the patient had a further pentagastrin test, an insulin test, and m e a s u r e m e n t s of serum gastrin concentration. In all patients, Visick grading was performed at each interview. Grade I represented an excellent result and grade II was given to patients with slight syrup-
toms that did not affect social or professional life. Grade III was given to patients who had moderate complaints but were definitely better than before operation, and Visick grade IV was assigned to treatment failure in patients who were not better, or were even worse than before the operation, according to their own opinion or to that of the surgeon.
Results
Reduction in Unstimulated Gastric Acid Secretion All 748 patients had a pentagastrin test before operation and 367 had further tests at 3 months and 1 year postoperatively. Results for BAO are given in Table 1. It appears that at 3 months the level of unstimulated secretion had not stabilized. Further changes occurred with time; patients with SGV + D and PCV with or without D showed a rise, statistically significant for the first mentioned group, and those with SGV + A had an insignificant further reduction. As an end result of this study, the median value was the same at 1 year for SGV + D and PCV with or without D, while patients with SGV + A had a considerably lower spontaneous secretion. Reduction in acid secretion was largest following SGV + A, while the other procedures reduced BAO to the same level.
Table 1. Reduction in unstimulated gastric acid secretion (BAO). At 1 year postoperatively the level of unstimulated gastric acid secretion (BAO) was the same for SGV + D, PCV, and PCV + D, but significantly lower when the antrum was removed (SGV + A). A significant rise in acid secretion occurred from 3 months to 1 year after surgery in patients treated with SGV + D (p < 0.001, paired t-test), while the rise after PCV and PCV + D and the decrease after SGV + A were not significant.
Basal acid secretion (BAO)--mEq/h Preoperative Postoperative SGV + D (n = 175) Median Interquartile range Range PCV (n = 131) Median Interquartile range Range S G V + A ( n = 24) Median Interquartile range Range P C V + D ( n = 37) Median Interquartile range Range
3.0 1.4-5.4 0-42.8
3 months 0.6 0-1.8 0-8.1
1 year 1.2 0.2-2.8 0-13.6
3.2 1.5-5.4 0-17.6
0.8 0.1-2.3 0-7.3
1.1 0.3-2.4 0-8.7
5.8 2.6-7.3 1.3-22.1
1.9 0.1-2.8 0-15.9
0.3 0-1.4 0-9.9
3.4 2.0-7.1 0-20.7
0.8 0.2-2.3 0-9.4
1.2 0.2-2.4 0-10.0
D. Andersen et al. : Aarhus County Vagntomy Trial, Part II
Reduction in Pentagastrin-Stimulated Gastric Acid Secretion
93
Visick Grading
The values of PAO pg in the same 367 patients, preoperatively and at 3 months and 1 year following surgery, are given in Table 2. Since no difference in reduction was observed between hypersecretors and hyposecretors, the results for all patients were pooled. Again, the level of acid secretion had not stabilized at 3 months. A significant increase with time was noted following PCV, and an insignificant increase was observed after SGV + D and PCV + D. PAO eg continued to decrease from 3 months to 1 year after SGV + A, but not significantly. Reduction at 1 year was 95% after SGV + A, approximately 60% after either SGV + D or PCV + D, and 44% after PCV (Table 3).
The overall clinical assessment [2] includes sequelae, continued dyspepsia, and ulcer recurrences during the observation period. At 2 years postoperatively, the material consisted of 395 patients. Of these, 24 had a recurrent ulcer. The clinical grading is shown in Table 4, the reasons for treatment failure in Table 5, and the final clinical grading after treatment of the failures in Table 6. The final clinical grading represents the evaluation of the patients, shown in Table 4, at least 1 year after treatment of the failure. Two patients in the PCV + D group and 2 patients in the PCV group had an observation time of less than 1 year after reoperation and could not be included. At this stage, the percentage of failure was the same after SGV + D and PCV, while the percent-
Table 2. Reduction in pentagastrin-stimulated gastric acid secretion. Peak acid output following pentagastrin (PAOTM)was reduced considerably less in patients treated with PCV than following SGV + A. SGV + D and PCV + D resulted in the same reduction. The rise in PAOPgwith time was significant for PCV (p < 0.001, paired t-test), but insignificant for SGV + D and PCV + D. The further decrease observed for SGV + A after 3 months was not significant. Peak stimulated acid secretion (PAOVg)--mEq/h
SGV + D (n = 175) Median Interquartile range Range PCV (n = 131) Median Interquartile range Range S G V + A ( n = 24) Median Interquartile range Range P C V + D ( n = 37) Median Interquartile range Range
Preoperative
Postoperative
32.8 28.2-42.8 12.6--74.3
3 months 11.6 7.0-19.8 0-53.8
1 year 13.0 7.8-21.0 0-76.0
39.6 30.2-50.2 9.0-87.8
18.6 11.0-27.2 0.1-56.2
21.4 15.4-30.0 0.8-53.2
54.4 48.2-60.6 45.0-72.5
5.4 2.4-7.8 0-37.6
2.4 1.0-4.4 0-19.6
34.7 26.7-45.8 11.4- 67.6
12.0 8.5-21.6 0-47.6
15.2 7.2-21.2 0-50.2
Table 3. Percent reduction in pentagastrin-stimulated gastric acid secretion after ulcer operations. The percent reduction in peak acid output after pentagastrin (PAO e~) decreased insignificantly from 3 months to 1 year following SGV + D, was approximately unchanged after PCV + D, and was significantly less after PCV. 3 months postoperatively Operation
Number
Median
Interquartile range
SGV + D SGV + A PCV + D PCV
175 24 37 131
62.8 90.5 52.6 54.5
47.0-77.9 83.8-95.3 43.4-74.9 36.5-69.0
Range
1 year postoperatively Interquartile Median range
Range
0-100 33.8-100 0-100 0-100
59.0 95.1 56.8 44.0
0-100 67.6--100 13.9-98.7 0-96.9
44.6-76.7 91.6-97.8 45.7-77.2 30.5-59.4
94
World J. Surg. Vol. 2, No. 1, January, 1978
age of excellent results was higher among patients treated with PCV.
Probability of Ulcer Recurrence Of the 748 patients who were observed for up to 5 years, 38 developed a recurrent ulcer. Recurrence developed in 15 of 353 patients after SGV + D, none of 54 patients after SGV + A, 3 of 68 patients after PCV + D, and 20 of 273 patients after PCV. Due to the great variation in observation time these figures are of limited value. Thus, of the 748 patients, 553 had a postoperative observation period of 1 year, 395 of 2 years, 219 of 3 years, 95 of 4 years, and 4 of 5 years. N o relationship between recurrence and either sex or gastric acid secretion could be established. Evaluation of ulcer recurrence rate must include not only the n u m b e r of patients with recurrence but also the time of recurrence and the n u m b e r of patients at risk of recurrence during the observation period. A detailed analysis was limited to SGV + D and PCV, since only these groups had a sufficient n u m b e r of patients and recurrences to permit an analysis. In these 2 groups, a total of 35 recurrences took place during a total of approximately 15,000 Table 4. Visick clinical grading of 395 patients available for follow-up 2 years after operation. The number of failures was significantly higher after PCV with or without D than after either SGV + D or SGV + A. Number of patients Visick grading
SGV + D
SGV + A
PCV + D
PCV
Excellent (grade I) Good (grade II) Satisfactory (grade III) Failure (grade IV) Total patients
113 48 15 16 192
17 8 5 2 32
25 7 1 __6 39
93 17 5 17 132
patient-months of observation. Calculations were made of survival without ulcer recurrence (S[t]), recurrence risk (h[t]), and integrated recurrence risk (/3It]). A life table method modified for incomplete follow-up and for small patient material was used to calculate survival without recurrence [3]. At the time (t) for each recurrence, we calculated the probability of survival without recurrence after this time (1 - 1/ NO, where Nt represents the n u m b e r of patients under observation. These probabilities were multiplied and plotted along the time axis. The mathematical expression behind this calculation is S(t) =
ft c
where f(u) represents the probability of recurrence within a small time interval. In Figs. 1 and 2 are shown graphs (Kaplan-Meier plots) of the functions (1 - Sit] ), since it is usual in clinical publications to give the probability of having a recurrence within a certain period of observation, and not the probability of survival without a recurrence beyond this time. Calculations based on the patients treated with PCV or SGV + D show a probability of recurrence within 30 months of approximately 11% after PCV and 6% after S G V + D (Fig. 1). No recurrences were observed in the 318 patients observed for more than 30 months. When the PCV group was divided into 2 subgroups according to the location of the primary ulcer, we found an excessively high probability of ulcer recurrence (22%) in patients with pyloric ulcer (PU) and prepyloric ulcer (PPU), while the recurrence rate for duodenal bulb ulcers (DU) was similar to that after SGV + D. At the time (t) for each recurrence, we calculated the probability of having a recurrence (I/N0, and for this value we used the symbol X(t) to represent the recurrence risk. The values for X(t) were summed up and plotted along the time axis in a Nelson plot [4].
Table 5. Reason for classifying patients as Visick grade IV in 395 patients available for follow-up 2 years postoperatively. Following PCV the main reason for registration in Visick grade IV was a recurrent ulcer, while after SGV + D dyspepsia and dumping were responsible just as often as recurrence. Number of patients Reason for Visick grade IV Recurrent ulcer Reoperation for gastric retention Dyspepsia Dumping Total failures
SGV + D n = 192 8 1 4 3 16 (8%)
f(u)du,
SGV + A n = 32
PCV + D n = 39
PCV n = 132
0 1 1 0 2 (6%)
3 0 I 2 6 (15%)
13 2 2 0 17 (13%)
D. Andersen et al.: Aarhus County Vagotomy Trial, Part II
95
Table 6. Final Visick grading after treatment of the failures (usually by antrectomy for recurrent ulcer) in the 395 patients followed up for 2 years and listed in Tables 4 and 5. In patients treated with SGV + D the number of failures was reduced from 16 to 8 (1 nonoperated patient with recurrent ulcer, 4 with dyspepsia but no ulcer, and 3 with incapacitating dumping). The group treated with SGV + A was unchanged. Two patients initially treated wtih PCV + D underwent reoperations, one for recurrent ulcer and one for dumping, but the observation time is still too short for inclusion in the final clinical grading. The 3 patients remaining in the failure group included one with an unoperated recurrence and 2 with dyspepsia. Finally, 2 patients in the PCV group were excluded from the final grading; one died after antrectomy for recurrent ulcer, and in one the observation time is too short after antrectomy for recurrence. The 5 remaining failure patients included 3 who did not want reoperation for recurrence and 2 with dyspepsia but no ulcer on endoscopy and x-ray examination.
Number of patients Final Visick grading
SGV + D
SGV + A
PCV + D
Excellent Good Satisfactory Failure
117 (61%) 51 16 8 (4%)
17 (53%) 8 6 1 (3%)
26 (70%) 7 1 3 (8%)
192
32
37
Total patients
PCV 98 (75%) 22 5 5 (4%) 130 Kaplan Meier P I o t s ( 1 - ~ ( t ) ; f o r Recurrence Rate after
The mathematical expression underlying this procedure is
PCV and
t
fi(t) =
L
X(u)du,
where X(u) represents the risk of having a recurrence within a small time interval. The fi-plot offers a better illustration of the changes in recurrence risk over a time period than can be obtained by the Kaplan-Meier plot, although these plots are rather similar in situations where the recurrence risk is modest. When the plots are rectilinear, as is the case in Figs. 3 and 4, the recurrence risk X(t) is constant over the observation period and equal to the slope of the line. In this special case, the powerful and simple F-test can be used as a test of significance for differences between recurrence risks (rates). Figure 3 shows that the risk of having a recurrence after SGV + D was constant and equal to 0.21% per month from the beginning of the observation period up to 30 months postoperatively, after which time no further recurrences took place. After PCV the recurrence risk was constant and equal to 0.38% per month from the time of operation until 30 months postoperatively, after which no recurrences were seen. The difference between recurrence risks for SGV + D and PCV was significant (p < 0.05). Figure 4 shows that the recurrence risk was constant and significantly higher (0.96% per month) when PCV was used for pyloric or prepyloric ulcers than when it was used for duodenal bulb ulcers (0.26% per month) (p < 0.01). For SGV + D, recurrence risk was the same for all locations of ulcer,
c=
O.120
SGV+ D
O.100 0.080 0.060 "5 := 0.040
[
0+020 c~
lz
24
36
~
60
Months after operation
Fig. 1. The probability of ulcer recurrence as calculated by the method of Kaplan and Meier [3] in 353 patients treated with SGV + D and 273 treated with PCV, observed up to 5 years after sm gery. No recurrence developed later than 30 months postoperatively. The calculated probability for recurrence is approximately 6% after SGV + D and 11% after PCV.
and, therefore, the r-plot for SGV + D for all 3 sites of ulcer from Fig. 3 was included in Fig. 4 for comparison. The fi-plot shows that the recurrence risk for PCV when used for duodenal bulb ulcers was not significantly different from the recurrence risk for SGV + D.
Discussion
Basal secretion was reduced to approximately the same level following the 4 operations on trial. The peak of the pentagastrin-stimulated gastric acid secretion was reduced less after PCV than either after
96
World J. Surg. Vol. 2, No. 1, January, 1978
0.24 0.22 0.20
P~ua
0.22
SGV+ o
o.18
0.14
0.16
V
0.12
0.14 0.12
0,08
0.10
r .....
0.06 : 0.04.
-- 0.08-
DU FJ F
....
A = 0.0096
0,20
0.16
0.I0 o
PCV ( PU, P P U ) - PCV( DU ) --/
nd PPU
=
~
0,24 --
,~ 0,18 9"-
Nelson Plots ( # ( t )) for I ntegrated Recurrence Rateafter
Kaplan Meier Plots(1 ~ ( t ) l f o r Recurrence Rate after PCV
J ....
//"
~j
oo4OO / ooo
J
A = 0.0026
,
0.02 0.02 12
24
36
i~
Months after operation
24
Months after operation
Fig. 2. Probability of ulcer recurrence after PCV related to location of the ulcer. Of the patients treated with PCV, 214 had an ulcer located in the duodenal bulb (DU) and 59 had a pyloric or prepyloric ulcer (PU, PPU). The probability of having a recurrent ulcer when calculated as in Fig. 1 shows a great difference according to the location of the treated ulcer. Nelson Plots (# ( t )) for Integrated Recurrence Rate .Z
O. 120
~"
O.100
.~,/
PCV A = 0.0038
O.080
~
060 0.04O
S *J
/
o~
A
= 0.0021
o
0,0201
i2 Months after
24
36
operation
Fig. 3. Nelson plots for integrated recurrence risk after SGV + D (open circles) and PCV (closed circles). The recurrence risks (X), equal to the slope of the lines, were constant from the time of operation until 30 months postoperatively, but after that time they were zero, meaning that a continuation of the lines to the end of the maximal observation period of 60 months would have been horizontal. The recurrence risk was 0.38% per month after PCV and 0.21% per month after SGV + D (p < 0.05). SGV + D or PCV + D. The technical denervation of the parietal cell mass should be equally complete in PCV with and without D so that a question arises regarding differences in the completeness of aspiration during performance of the gastric secretory studies. Studies of this possibility are in progress. The clinical grading according to the Visick system showed a higher frequency of failures after PCV than after SGV + D. However, the reasons for the
Fig. 4. Nelson plots for integrated recurrence risk (see text) after PCV for duodenal ulcer (DU) (open circles) and for pyloric ulcer (PU) or prepyloric ulcer (PPU) (closed circles). The recurrence risks (X), equal to the slope of the lines, were constant from the time of operation until 30 months postoperatively, but after that time they were zero, meaning that a continuation of the lines to the end of the maximal observation period of 60 months would have been horizontal. The recurrence risk was 0.96% per month when PCV was used for PU or PPU and 0.26% per month when used for DU. This difference was significant (p < 0.01). The plot for SGV + D, taken from Fig. 3, is shown for comparison, and it differs only slightly and insignificantly from the plot for PCV used for DU. failures were different for the 2 procedures. Only one-haft of the failures after SGV + D were due to ulcer recurrence, while this cause accounted for most of the failures after PCV. After treatment of recurrent ulcer, the failure rate was reduced from 13 to 4% after PCV and from 8 to 4% after SGV + D, in keeping with previous observations showing that recurrence is easier to treat than severe sequelae. The Visick grading system is a useful method of evaluation of chronic symptoms due to sequelae and continued chronic dyspepsia. However, it is uncertain how recurrent ulcer should be placed within this grading system. Is an episode of dyspepsia and concomitant demonstration of a recurrent ulcer a reason for permanently placing these patients in the failure group, even if the ulcer heals spontaneously and does not recur? We have followed this principle in the present communication but have doubts about continuing this practice. According to the calculations of the probabilities of ulcer recurrence, it might be expected that the recurrence rate will be 6% after SGV + D and 11% after PCV. The predicted recurrence rate for SGV + D is similar to the actual recurrence rate reported by
D. Andersen et al. : Aarhus County Vagotomy Trial, Part II
other authors [5, 6], so that it is probable that the predicted recurrence rate calculated for PCV represents a realistic guess for the future. The surgeon and the patient should then balance the higher recurrence rate after PCV against the lower rate of sequelae [1]. An unexpected observation in the present study was the highly significant difference in the results of PCV for duodenal ulcer and PCV for pyloric and prepyloric ulcer. This difference may mean that PCV is not the operation of choice in patients with a pyloric or a prepyloric ulcer. In such patients SGV + D achieved the same results as in patients with duodenal ulcer. One can speculate whether the drainage or the denervation of the antrum, or the combination of the two, has the greatest influence on healing of a prepyloric ulcer. The results in our group of patients treated with PCV + D may provide the solution to this question, but the number of recurrences and the observation time are at present insufficient. Another interesting observation was the constant risk of recurrence from month to month during the first 21/2 years for both SGV + D and PCV, and for both D U and PPU. We expected the recurrences to accumulate at a certain time during the observation period and only the statistical method used to analyze the data revealed the linear course of the cumulative recurrence risk. It is also remarkable that no recurrences occurred after 30 monthg in over 318 patients under observation. However, further observation is needed, particularly in view of the incidence of late recurrences observed in the Danish PCV pilot series [7]. In conclusion, it appears that we are perhaps approaching the time when the final prognosis for PCV can be evaluated, On the basis of our experience to date, PCV is the operation of choice in patients with nonobstructing duodenal ulcer, because it has a recurrence rate about equal to other operations, but has substantially fewer severe sequelae. For unknown reasons PCV seems to have a higher recurrence rate when used for pyloric and prepyloric ulcers, and the choice of operation must weigh the higher risk of recurrence against the lower risk of sequelae.
Rrsum6
Dans une 6tude clinique prospective, 748 malades atteints d'ulc~re duodrnal (DU) ou prr-pylorique (PPU) ont subi une vagotomie, avec rrpartition par tirage au sort en: 353 vagotomies s61ectives avec drainage gastrique (SGV + D), 54 vagotomies srlectives avec antrectomie (SGV + A), 273 vagotomies super-s61ectives (PCV) et 68 vagotomies super-s61ec-
97
tives avec drainage gastrique (PCV + D). Au 3e mois post-oprratoire, la s6cr6tion acide basale (BAO) n'est pas stabilis6e. Pendant l'ann6e suivante, BAO diminue aprrs SGV + A; elle augmente dans les autres groupes, et de fagon significative apr~s SGV + D. Un an apr~s l'oprration, BAO est la m r m e pour les 3 op6rations qui ne comportent pas d' antrectomie. Le d6bit d'acide maximum apr~s pentagastrine (PAOPg) continue h d6croitre entre le 3e mois et la 16re annre post-op6ratoires aprrs SGV + A; il augmente apr~s les autres oprrations, et de fagon significative aprrs PCV. Apr~s 1 an, PAOPg est r6duit de 90% aprrs SGV + A, de 45% aprrs PCV et de + 60% aprbs SGV + D et PCV + D. Au point de vue clinique, les 6checs sont plus nombreux apr6s PCV qu'aprrs SGV. Comme la plupart des 6checs aprbs PCV sont des r6cidives ulc6reuses, l'estimation clinique finale (apr~s traitement des 6checs) r6v~le un hombre 6gal de mauvais rrsultats pour les deux op6rations. L a probabilit6 de r6cidive ulc6reuse est de 6% aprrs SGV + D et de 11% apr~s PCV. Mais ce calcul global ne tient pas compte de la localisation de l'ulc~re. En fait, la frrquence des r6cidives est la m r m e apr~s SGV + D pour D U e t PPU et apr~s PCV pour DU; par contre, il y a 22% de rrcidives apr~s PCV pour PPU. L e risque de r6cidive reste constant de mois en mois pendant les 21}z premitres ann6es: apr~s cette date, nous n'avons plus" observ6 de r6cidives. L ' r t u d e suggrre donc que, pour DU, PCV est pr6frrable ~t SGV + D: le risque de r6cidive est le m~me, mais les srquelles sont moins nombreuses. Pour PPU, PCV accroit le risque de r6cidive.
References
1. Amdrup, E., Andersen, D., H0strup, H.: The Aarhus County vagotomy trial. I. An interim report on primary results and incidence of sequelae following parietal cell vagotomy and selective gastric vagotomy in 748 patients. World J. Surg. 2:85, 1978 2. Visick, A.H.: The study of the failures after gastrectomy. Ann. R. Coll. Surg. Engl. 3:266, 1968 3. Kaplan, E.L., Meier, P.: Non-parametric estimation from incomplete observations. J. Am. Statist. Assoc. 53:457, 1958 4. Nelson, W.: Hazard plotting for incomplete failure data. J. Qual. Techn. 2:126, 1970 5. De Miguel, J.: Late results of bilateral selective vagotomy and pyloroplasty for duodenal ulcer: 5-9 years follow-up. Br. J. Surg. 61:264, 1974 6. Amdrup, E., Jensen, H.-E.: One hundred patients five years after selective gastric vagotomy and drainage for duodenal ulcer. Surgery 74:321, 1973 7. Jensen, H.-E., Amdrup, E.: One hundred patients 5-8 years after parietal cell vagotomy. World J. Surg. (in
press)
The Aarhus County Vagotomy Trial I I . A n I n t e r i m R e p o r t on R e d u c t i o n in A c i d S e c r e t i o n a n d U l c e r R e c u r r e n c e R a t e F o l l o w i n g P a r i e t a l Ceil V a g o t o m y a n d Selective G a s t r i c V a g o t o m y Daniel Andersen, M.D., Ph.D., Hans Hr M.D., Ph.D., and Erik Amdrup, M.D., Ph.D. Department of Surgical Gastroenterology, Amtssygehuset and Kommunehospitalet, Aarhus, and Department of Surgery, Centralsygehuset, Randers, University of Aarhus, Denmark
rence was found to be constant from month to month during the first 21/2 years, after which no new recurrent ulcers were observed. It is suggested that for DU, PCV is preferable to SGV + D because the recurrence rate is the same but the incidence of sequelae is lower. When PCV is used for PPU, a higher ulcer recurrence rate may be expected.
In a prospective clinical trial, vagotomy for duodenal ulcer (DU) and prepylorie ulcer (PPU) was performed in 748 patients, 353 of whom were randomly allocated to selective gastric vagotomy and drainage (SGV + D), 54 to SGV + antrectomy (A), 273 to parietal cell vagotomy (PCV), and 68 to PCV + D. By 3 months postoperatively, basal acid secretion (BAO) had not stabilized. During the following year patients with SGV + A showed a decrease, while those with the other operations showed a rise in BAO, significant for SGV + D. One year after operation the level of BAO was the same after the 3 operations that did not remove the antrum. Peak acid output after pentagastrin stimulation (PAOpg) continued to decrease from 3 months to 1 year after SGV + A, while the other operations were followed by an increase, statistically significant for PCV. After 1 year the postoperative reduction in PAO pg was 90% for SGV + A, 45% for PCV, and approximately 60% for SGV + D and PCV + D. Overall clinical grading showed more failures following PCV than after SGV. Since failures after PCV were mainly ulcer recurrences, the final grading (after treatment of the failures) showed an equal number of failures for the 2 operations. Calculation of the probability of ulcer recurrence suggested a 6% rate after SGV + D and an 11% rate after PCV. However, when calculations took into account the location of the primary ulcer, the recurrence rate was the same after SGV + D for DU and PPU, while PCV showed a similar rate when used for DU but an incidence of 22% when used for PPU. The risk of recur-
In p a r t I o f this i n t e r i m r e p o r t [ 1] a c o n t r o l l e d trial was described involving patients with proven duodenal ulcer who were electively treated by parietal cell v a g o t o m y (PCV) w i t h o r w i t h o u t d r a i n a g e (D), a n d s e l e c t i v e gastric v a g o t o m y ( S G V ) w i t h D o r a n t r e c t o m y (A). D e t a i l s w e r e g i v e n o f t h e r a n d o m i zation method, intraoperative and postoperative c o m p l i c a t i o n s , a n d the i n c i d e n c e o f s e q u e l a e as j u d g e d at the 2 - y e a r f o l l o w - u p e x a m i n a t i o n . T h i s communication deals with the results of studies of gastric acid secretion performed 3 months and 1 year p o s t o p e r a t i v e l y , specifically t h e b a s a l a c i d o u t p u t ( B A O ) a n d the p e a k a c i d o u t p u t f o l l o w i n g p e n t a g a s trin s t i m u l a t i o n (PAOPg). F u r t h e r m o r e , o b s e r v a t i o n s a r e r e p o r t e d o n the u l c e r r e c u r r e n c e r a t e a f t e r 2 y e a r s o f f o l l o w - u p , a n d the i n t e g r a t e d r e c u r r e n c e r a t e for t h e t o t a l p a t i e n t m a t e r i a l d u r i n g t h e o b s e r v a tion y e a r s 1972-1977.
Aided by grant no. S L F 512-5456 from the Danish Medical Research Council. Reprint requests: Erik Amdrup, M.D., Ph.D., Surgical Gastroenterological Dpt. L, Kommunehospitalet, 8000 Aarhus C., Denmark.
0364-2313/78/0002-0091 $02.00 9 1978 Societ6 Internationale de Chirurgie
91
92
World J. Surg. Vol. 2, No. 1, January, 1978
Material and Methods
The trial involved 748 patients. According to random allocation, 353 had SGV + D, 54 SGV + A, 68 PCV + D, and 273 PCV without drainage. Five patients died during the early postoperative period. All patients underwent clinical examination 3 months and every year after surgery. A pentagastrin stimulation test was performed preoperatively and was repeated postoperatively at 3 months and 1 year. The fasting contents of the stomach were aspirated during a 15-minute period. BAO was then determined by aspiration during 4 periods of 15 minutes each. Pentagastrin in a dose of 6/xg/kg body weight was given intramuscularly, and the stimulated secretion was followed for 4 periods of 15 minutes each. Postoperatively the dose of pentagastrin was 10 tzg/ kg. Volume of gastric juice was measured and acid concentration was determined by titration to p H 7 with 0.1 N N a O H by an automatic titrator (Radiometer, Copenhagen). PAO pg was calculated from the 2 highest consecutive samples multiplied by 2. The patients who developed dyspeptic s y m p t o m s were investigated by endoscopy and also often had radiologic studies. If ulcer recurrence was found, the patient had a further pentagastrin test, an insulin test, and m e a s u r e m e n t s of serum gastrin concentration. In all patients, Visick grading was performed at each interview. Grade I represented an excellent result and grade II was given to patients with slight syrup-
toms that did not affect social or professional life. Grade III was given to patients who had moderate complaints but were definitely better than before operation, and Visick grade IV was assigned to treatment failure in patients who were not better, or were even worse than before the operation, according to their own opinion or to that of the surgeon.
Results
Reduction in Unstimulated Gastric Acid Secretion All 748 patients had a pentagastrin test before operation and 367 had further tests at 3 months and 1 year postoperatively. Results for BAO are given in Table 1. It appears that at 3 months the level of unstimulated secretion had not stabilized. Further changes occurred with time; patients with SGV + D and PCV with or without D showed a rise, statistically significant for the first mentioned group, and those with SGV + A had an insignificant further reduction. As an end result of this study, the median value was the same at 1 year for SGV + D and PCV with or without D, while patients with SGV + A had a considerably lower spontaneous secretion. Reduction in acid secretion was largest following SGV + A, while the other procedures reduced BAO to the same level.
Table 1. Reduction in unstimulated gastric acid secretion (BAO). At 1 year postoperatively the level of unstimulated gastric acid secretion (BAO) was the same for SGV + D, PCV, and PCV + D, but significantly lower when the antrum was removed (SGV + A). A significant rise in acid secretion occurred from 3 months to 1 year after surgery in patients treated with SGV + D (p < 0.001, paired t-test), while the rise after PCV and PCV + D and the decrease after SGV + A were not significant.
Basal acid secretion (BAO)--mEq/h Preoperative Postoperative SGV + D (n = 175) Median Interquartile range Range PCV (n = 131) Median Interquartile range Range S G V + A ( n = 24) Median Interquartile range Range P C V + D ( n = 37) Median Interquartile range Range
3.0 1.4-5.4 0-42.8
3 months 0.6 0-1.8 0-8.1
1 year 1.2 0.2-2.8 0-13.6
3.2 1.5-5.4 0-17.6
0.8 0.1-2.3 0-7.3
1.1 0.3-2.4 0-8.7
5.8 2.6-7.3 1.3-22.1
1.9 0.1-2.8 0-15.9
0.3 0-1.4 0-9.9
3.4 2.0-7.1 0-20.7
0.8 0.2-2.3 0-9.4
1.2 0.2-2.4 0-10.0
D. Andersen et al. : Aarhus County Vagntomy Trial, Part II
Reduction in Pentagastrin-Stimulated Gastric Acid Secretion
93
Visick Grading
The values of PAO pg in the same 367 patients, preoperatively and at 3 months and 1 year following surgery, are given in Table 2. Since no difference in reduction was observed between hypersecretors and hyposecretors, the results for all patients were pooled. Again, the level of acid secretion had not stabilized at 3 months. A significant increase with time was noted following PCV, and an insignificant increase was observed after SGV + D and PCV + D. PAO eg continued to decrease from 3 months to 1 year after SGV + A, but not significantly. Reduction at 1 year was 95% after SGV + A, approximately 60% after either SGV + D or PCV + D, and 44% after PCV (Table 3).
The overall clinical assessment [2] includes sequelae, continued dyspepsia, and ulcer recurrences during the observation period. At 2 years postoperatively, the material consisted of 395 patients. Of these, 24 had a recurrent ulcer. The clinical grading is shown in Table 4, the reasons for treatment failure in Table 5, and the final clinical grading after treatment of the failures in Table 6. The final clinical grading represents the evaluation of the patients, shown in Table 4, at least 1 year after treatment of the failure. Two patients in the PCV + D group and 2 patients in the PCV group had an observation time of less than 1 year after reoperation and could not be included. At this stage, the percentage of failure was the same after SGV + D and PCV, while the percent-
Table 2. Reduction in pentagastrin-stimulated gastric acid secretion. Peak acid output following pentagastrin (PAOTM)was reduced considerably less in patients treated with PCV than following SGV + A. SGV + D and PCV + D resulted in the same reduction. The rise in PAOPgwith time was significant for PCV (p < 0.001, paired t-test), but insignificant for SGV + D and PCV + D. The further decrease observed for SGV + A after 3 months was not significant. Peak stimulated acid secretion (PAOVg)--mEq/h
SGV + D (n = 175) Median Interquartile range Range PCV (n = 131) Median Interquartile range Range S G V + A ( n = 24) Median Interquartile range Range P C V + D ( n = 37) Median Interquartile range Range
Preoperative
Postoperative
32.8 28.2-42.8 12.6--74.3
3 months 11.6 7.0-19.8 0-53.8
1 year 13.0 7.8-21.0 0-76.0
39.6 30.2-50.2 9.0-87.8
18.6 11.0-27.2 0.1-56.2
21.4 15.4-30.0 0.8-53.2
54.4 48.2-60.6 45.0-72.5
5.4 2.4-7.8 0-37.6
2.4 1.0-4.4 0-19.6
34.7 26.7-45.8 11.4- 67.6
12.0 8.5-21.6 0-47.6
15.2 7.2-21.2 0-50.2
Table 3. Percent reduction in pentagastrin-stimulated gastric acid secretion after ulcer operations. The percent reduction in peak acid output after pentagastrin (PAO e~) decreased insignificantly from 3 months to 1 year following SGV + D, was approximately unchanged after PCV + D, and was significantly less after PCV. 3 months postoperatively Operation
Number
Median
Interquartile range
SGV + D SGV + A PCV + D PCV
175 24 37 131
62.8 90.5 52.6 54.5
47.0-77.9 83.8-95.3 43.4-74.9 36.5-69.0
Range
1 year postoperatively Interquartile Median range
Range
0-100 33.8-100 0-100 0-100
59.0 95.1 56.8 44.0
0-100 67.6--100 13.9-98.7 0-96.9
44.6-76.7 91.6-97.8 45.7-77.2 30.5-59.4
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World J. Surg. Vol. 2, No. 1, January, 1978
age of excellent results was higher among patients treated with PCV.
Probability of Ulcer Recurrence Of the 748 patients who were observed for up to 5 years, 38 developed a recurrent ulcer. Recurrence developed in 15 of 353 patients after SGV + D, none of 54 patients after SGV + A, 3 of 68 patients after PCV + D, and 20 of 273 patients after PCV. Due to the great variation in observation time these figures are of limited value. Thus, of the 748 patients, 553 had a postoperative observation period of 1 year, 395 of 2 years, 219 of 3 years, 95 of 4 years, and 4 of 5 years. N o relationship between recurrence and either sex or gastric acid secretion could be established. Evaluation of ulcer recurrence rate must include not only the n u m b e r of patients with recurrence but also the time of recurrence and the n u m b e r of patients at risk of recurrence during the observation period. A detailed analysis was limited to SGV + D and PCV, since only these groups had a sufficient n u m b e r of patients and recurrences to permit an analysis. In these 2 groups, a total of 35 recurrences took place during a total of approximately 15,000 Table 4. Visick clinical grading of 395 patients available for follow-up 2 years after operation. The number of failures was significantly higher after PCV with or without D than after either SGV + D or SGV + A. Number of patients Visick grading
SGV + D
SGV + A
PCV + D
PCV
Excellent (grade I) Good (grade II) Satisfactory (grade III) Failure (grade IV) Total patients
113 48 15 16 192
17 8 5 2 32
25 7 1 __6 39
93 17 5 17 132
patient-months of observation. Calculations were made of survival without ulcer recurrence (S[t]), recurrence risk (h[t]), and integrated recurrence risk (/3It]). A life table method modified for incomplete follow-up and for small patient material was used to calculate survival without recurrence [3]. At the time (t) for each recurrence, we calculated the probability of survival without recurrence after this time (1 - 1/ NO, where Nt represents the n u m b e r of patients under observation. These probabilities were multiplied and plotted along the time axis. The mathematical expression behind this calculation is S(t) =
ft c
where f(u) represents the probability of recurrence within a small time interval. In Figs. 1 and 2 are shown graphs (Kaplan-Meier plots) of the functions (1 - Sit] ), since it is usual in clinical publications to give the probability of having a recurrence within a certain period of observation, and not the probability of survival without a recurrence beyond this time. Calculations based on the patients treated with PCV or SGV + D show a probability of recurrence within 30 months of approximately 11% after PCV and 6% after S G V + D (Fig. 1). No recurrences were observed in the 318 patients observed for more than 30 months. When the PCV group was divided into 2 subgroups according to the location of the primary ulcer, we found an excessively high probability of ulcer recurrence (22%) in patients with pyloric ulcer (PU) and prepyloric ulcer (PPU), while the recurrence rate for duodenal bulb ulcers (DU) was similar to that after SGV + D. At the time (t) for each recurrence, we calculated the probability of having a recurrence (I/N0, and for this value we used the symbol X(t) to represent the recurrence risk. The values for X(t) were summed up and plotted along the time axis in a Nelson plot [4].
Table 5. Reason for classifying patients as Visick grade IV in 395 patients available for follow-up 2 years postoperatively. Following PCV the main reason for registration in Visick grade IV was a recurrent ulcer, while after SGV + D dyspepsia and dumping were responsible just as often as recurrence. Number of patients Reason for Visick grade IV Recurrent ulcer Reoperation for gastric retention Dyspepsia Dumping Total failures
SGV + D n = 192 8 1 4 3 16 (8%)
f(u)du,
SGV + A n = 32
PCV + D n = 39
PCV n = 132
0 1 1 0 2 (6%)
3 0 I 2 6 (15%)
13 2 2 0 17 (13%)
D. Andersen et al.: Aarhus County Vagotomy Trial, Part II
95
Table 6. Final Visick grading after treatment of the failures (usually by antrectomy for recurrent ulcer) in the 395 patients followed up for 2 years and listed in Tables 4 and 5. In patients treated with SGV + D the number of failures was reduced from 16 to 8 (1 nonoperated patient with recurrent ulcer, 4 with dyspepsia but no ulcer, and 3 with incapacitating dumping). The group treated with SGV + A was unchanged. Two patients initially treated wtih PCV + D underwent reoperations, one for recurrent ulcer and one for dumping, but the observation time is still too short for inclusion in the final clinical grading. The 3 patients remaining in the failure group included one with an unoperated recurrence and 2 with dyspepsia. Finally, 2 patients in the PCV group were excluded from the final grading; one died after antrectomy for recurrent ulcer, and in one the observation time is too short after antrectomy for recurrence. The 5 remaining failure patients included 3 who did not want reoperation for recurrence and 2 with dyspepsia but no ulcer on endoscopy and x-ray examination.
Number of patients Final Visick grading
SGV + D
SGV + A
PCV + D
Excellent Good Satisfactory Failure
117 (61%) 51 16 8 (4%)
17 (53%) 8 6 1 (3%)
26 (70%) 7 1 3 (8%)
192
32
37
Total patients
PCV 98 (75%) 22 5 5 (4%) 130 Kaplan Meier P I o t s ( 1 - ~ ( t ) ; f o r Recurrence Rate after
The mathematical expression underlying this procedure is
PCV and
t
fi(t) =
L
X(u)du,
where X(u) represents the risk of having a recurrence within a small time interval. The fi-plot offers a better illustration of the changes in recurrence risk over a time period than can be obtained by the Kaplan-Meier plot, although these plots are rather similar in situations where the recurrence risk is modest. When the plots are rectilinear, as is the case in Figs. 3 and 4, the recurrence risk X(t) is constant over the observation period and equal to the slope of the line. In this special case, the powerful and simple F-test can be used as a test of significance for differences between recurrence risks (rates). Figure 3 shows that the risk of having a recurrence after SGV + D was constant and equal to 0.21% per month from the beginning of the observation period up to 30 months postoperatively, after which time no further recurrences took place. After PCV the recurrence risk was constant and equal to 0.38% per month from the time of operation until 30 months postoperatively, after which no recurrences were seen. The difference between recurrence risks for SGV + D and PCV was significant (p < 0.05). Figure 4 shows that the recurrence risk was constant and significantly higher (0.96% per month) when PCV was used for pyloric or prepyloric ulcers than when it was used for duodenal bulb ulcers (0.26% per month) (p < 0.01). For SGV + D, recurrence risk was the same for all locations of ulcer,
c=
O.120
SGV+ D
O.100 0.080 0.060 "5 := 0.040
[
0+020 c~
lz
24
36
~
60
Months after operation
Fig. 1. The probability of ulcer recurrence as calculated by the method of Kaplan and Meier [3] in 353 patients treated with SGV + D and 273 treated with PCV, observed up to 5 years after sm gery. No recurrence developed later than 30 months postoperatively. The calculated probability for recurrence is approximately 6% after SGV + D and 11% after PCV.
and, therefore, the r-plot for SGV + D for all 3 sites of ulcer from Fig. 3 was included in Fig. 4 for comparison. The fi-plot shows that the recurrence risk for PCV when used for duodenal bulb ulcers was not significantly different from the recurrence risk for SGV + D.
Discussion
Basal secretion was reduced to approximately the same level following the 4 operations on trial. The peak of the pentagastrin-stimulated gastric acid secretion was reduced less after PCV than either after
96
World J. Surg. Vol. 2, No. 1, January, 1978
0.24 0.22 0.20
P~ua
0.22
SGV+ o
o.18
0.14
0.16
V
0.12
0.14 0.12
0,08
0.10
r .....
0.06 : 0.04.
-- 0.08-
DU FJ F
....
A = 0.0096
0,20
0.16
0.I0 o
PCV ( PU, P P U ) - PCV( DU ) --/
nd PPU
=
~
0,24 --
,~ 0,18 9"-
Nelson Plots ( # ( t )) for I ntegrated Recurrence Rateafter
Kaplan Meier Plots(1 ~ ( t ) l f o r Recurrence Rate after PCV
J ....
//"
~j
oo4OO / ooo
J
A = 0.0026
,
0.02 0.02 12
24
36
i~
Months after operation
24
Months after operation
Fig. 2. Probability of ulcer recurrence after PCV related to location of the ulcer. Of the patients treated with PCV, 214 had an ulcer located in the duodenal bulb (DU) and 59 had a pyloric or prepyloric ulcer (PU, PPU). The probability of having a recurrent ulcer when calculated as in Fig. 1 shows a great difference according to the location of the treated ulcer. Nelson Plots (# ( t )) for Integrated Recurrence Rate .Z
O. 120
~"
O.100
.~,/
PCV A = 0.0038
O.080
~
060 0.04O
S *J
/
o~
A
= 0.0021
o
0,0201
i2 Months after
24
36
operation
Fig. 3. Nelson plots for integrated recurrence risk after SGV + D (open circles) and PCV (closed circles). The recurrence risks (X), equal to the slope of the lines, were constant from the time of operation until 30 months postoperatively, but after that time they were zero, meaning that a continuation of the lines to the end of the maximal observation period of 60 months would have been horizontal. The recurrence risk was 0.38% per month after PCV and 0.21% per month after SGV + D (p < 0.05). SGV + D or PCV + D. The technical denervation of the parietal cell mass should be equally complete in PCV with and without D so that a question arises regarding differences in the completeness of aspiration during performance of the gastric secretory studies. Studies of this possibility are in progress. The clinical grading according to the Visick system showed a higher frequency of failures after PCV than after SGV + D. However, the reasons for the
Fig. 4. Nelson plots for integrated recurrence risk (see text) after PCV for duodenal ulcer (DU) (open circles) and for pyloric ulcer (PU) or prepyloric ulcer (PPU) (closed circles). The recurrence risks (X), equal to the slope of the lines, were constant from the time of operation until 30 months postoperatively, but after that time they were zero, meaning that a continuation of the lines to the end of the maximal observation period of 60 months would have been horizontal. The recurrence risk was 0.96% per month when PCV was used for PU or PPU and 0.26% per month when used for DU. This difference was significant (p < 0.01). The plot for SGV + D, taken from Fig. 3, is shown for comparison, and it differs only slightly and insignificantly from the plot for PCV used for DU. failures were different for the 2 procedures. Only one-haft of the failures after SGV + D were due to ulcer recurrence, while this cause accounted for most of the failures after PCV. After treatment of recurrent ulcer, the failure rate was reduced from 13 to 4% after PCV and from 8 to 4% after SGV + D, in keeping with previous observations showing that recurrence is easier to treat than severe sequelae. The Visick grading system is a useful method of evaluation of chronic symptoms due to sequelae and continued chronic dyspepsia. However, it is uncertain how recurrent ulcer should be placed within this grading system. Is an episode of dyspepsia and concomitant demonstration of a recurrent ulcer a reason for permanently placing these patients in the failure group, even if the ulcer heals spontaneously and does not recur? We have followed this principle in the present communication but have doubts about continuing this practice. According to the calculations of the probabilities of ulcer recurrence, it might be expected that the recurrence rate will be 6% after SGV + D and 11% after PCV. The predicted recurrence rate for SGV + D is similar to the actual recurrence rate reported by
D. Andersen et al. : Aarhus County Vagotomy Trial, Part II
other authors [5, 6], so that it is probable that the predicted recurrence rate calculated for PCV represents a realistic guess for the future. The surgeon and the patient should then balance the higher recurrence rate after PCV against the lower rate of sequelae [1]. An unexpected observation in the present study was the highly significant difference in the results of PCV for duodenal ulcer and PCV for pyloric and prepyloric ulcer. This difference may mean that PCV is not the operation of choice in patients with a pyloric or a prepyloric ulcer. In such patients SGV + D achieved the same results as in patients with duodenal ulcer. One can speculate whether the drainage or the denervation of the antrum, or the combination of the two, has the greatest influence on healing of a prepyloric ulcer. The results in our group of patients treated with PCV + D may provide the solution to this question, but the number of recurrences and the observation time are at present insufficient. Another interesting observation was the constant risk of recurrence from month to month during the first 21/2 years for both SGV + D and PCV, and for both D U and PPU. We expected the recurrences to accumulate at a certain time during the observation period and only the statistical method used to analyze the data revealed the linear course of the cumulative recurrence risk. It is also remarkable that no recurrences occurred after 30 monthg in over 318 patients under observation. However, further observation is needed, particularly in view of the incidence of late recurrences observed in the Danish PCV pilot series [7]. In conclusion, it appears that we are perhaps approaching the time when the final prognosis for PCV can be evaluated, On the basis of our experience to date, PCV is the operation of choice in patients with nonobstructing duodenal ulcer, because it has a recurrence rate about equal to other operations, but has substantially fewer severe sequelae. For unknown reasons PCV seems to have a higher recurrence rate when used for pyloric and prepyloric ulcers, and the choice of operation must weigh the higher risk of recurrence against the lower risk of sequelae.
Rrsum6
Dans une 6tude clinique prospective, 748 malades atteints d'ulc~re duodrnal (DU) ou prr-pylorique (PPU) ont subi une vagotomie, avec rrpartition par tirage au sort en: 353 vagotomies s61ectives avec drainage gastrique (SGV + D), 54 vagotomies srlectives avec antrectomie (SGV + A), 273 vagotomies super-s61ectives (PCV) et 68 vagotomies super-s61ec-
97
tives avec drainage gastrique (PCV + D). Au 3e mois post-oprratoire, la s6cr6tion acide basale (BAO) n'est pas stabilis6e. Pendant l'ann6e suivante, BAO diminue aprrs SGV + A; elle augmente dans les autres groupes, et de fagon significative apr~s SGV + D. Un an apr~s l'oprration, BAO est la m r m e pour les 3 op6rations qui ne comportent pas d' antrectomie. Le d6bit d'acide maximum apr~s pentagastrine (PAOPg) continue h d6croitre entre le 3e mois et la 16re annre post-op6ratoires aprrs SGV + A; il augmente apr~s les autres oprrations, et de fagon significative aprrs PCV. Apr~s 1 an, PAOPg est r6duit de 90% aprrs SGV + A, de 45% aprrs PCV et de + 60% aprbs SGV + D et PCV + D. Au point de vue clinique, les 6checs sont plus nombreux apr6s PCV qu'aprrs SGV. Comme la plupart des 6checs aprbs PCV sont des r6cidives ulc6reuses, l'estimation clinique finale (apr~s traitement des 6checs) r6v~le un hombre 6gal de mauvais rrsultats pour les deux op6rations. L a probabilit6 de r6cidive ulc6reuse est de 6% aprrs SGV + D et de 11% apr~s PCV. Mais ce calcul global ne tient pas compte de la localisation de l'ulc~re. En fait, la frrquence des r6cidives est la m r m e apr~s SGV + D pour D U e t PPU et apr~s PCV pour DU; par contre, il y a 22% de rrcidives apr~s PCV pour PPU. L e risque de r6cidive reste constant de mois en mois pendant les 21}z premitres ann6es: apr~s cette date, nous n'avons plus" observ6 de r6cidives. L ' r t u d e suggrre donc que, pour DU, PCV est pr6frrable ~t SGV + D: le risque de r6cidive est le m~me, mais les srquelles sont moins nombreuses. Pour PPU, PCV accroit le risque de r6cidive.
References
1. Amdrup, E., Andersen, D., H0strup, H.: The Aarhus County vagotomy trial. I. An interim report on primary results and incidence of sequelae following parietal cell vagotomy and selective gastric vagotomy in 748 patients. World J. Surg. 2:85, 1978 2. Visick, A.H.: The study of the failures after gastrectomy. Ann. R. Coll. Surg. Engl. 3:266, 1968 3. Kaplan, E.L., Meier, P.: Non-parametric estimation from incomplete observations. J. Am. Statist. Assoc. 53:457, 1958 4. Nelson, W.: Hazard plotting for incomplete failure data. J. Qual. Techn. 2:126, 1970 5. De Miguel, J.: Late results of bilateral selective vagotomy and pyloroplasty for duodenal ulcer: 5-9 years follow-up. Br. J. Surg. 61:264, 1974 6. Amdrup, E., Jensen, H.-E.: One hundred patients five years after selective gastric vagotomy and drainage for duodenal ulcer. Surgery 74:321, 1973 7. Jensen, H.-E., Amdrup, E.: One hundred patients 5-8 years after parietal cell vagotomy. World J. Surg. (in
press)
