Digest&e Diseases and Sciences, Vol. 36, No. 12 (December 1991), pp. 1697-1701
Effect of Partial Gastrectomy on Serum Anti-Helicobacter pylori Immunoglobulins in Peptic Ulcer Patients CORNELIS B.H.W. LAMERS, PAUL N.M.A. RIEU, ROELAND A. VEENENDAAL, WlM VAN DUIJN, G. JOHAN A. OFFERHAUS, HARRY J.M. JOOSTEN, and A. SALVADOR PElqA
Since biliary enterogastric reflux is suggested to eradicate gastric infection with Heiicobacter pylori (HP), we have investigated in a prospective randomized study the effect o f partial gastrectomy with either Billroth H or Roux-en- Y anastomosis on infection with HP as assessed by the titers o f lgG and IgA antibodies against HP in serum. These antibodies were measured by ELISA in serum of 22 patients before and at 10 days and 6, 15, and 24 months after either Billroth H (N = 11) or Roux-en-Y (N = 11) gastrectomy for peptic ulcer. All patients had HP demonstrated in their preoperative endoscopic gastric biopsies, The preoperative serum IgA antibodies against HP (anti-HP IgA) were increased in 20 o f the 22 patients (range 0.21-1.69) while the IgG antibodies (anti-HP IgG) were increased in all 22 patients (range 0.38-1,31). Four o f the Billroth H patients had clearance o f liP from gastric biopsies accompanied by rapid and pronounced decrease o f anti-HP IgA. In contrast, the patients with Roux-en-Y gastrectomy and the Billroth H patients with persistent HP infection had no change in anti-HP IgA after surgery. Anti-HP IgG showed variable results in the four patients without gastric HP infection and was not affected by gastrectomy in the patients with persistent HP infection. We concluded that serum anti-HP IgA, but not anti-HP IgG, is helpful in identifying those patients in whom HP is no longer demonstrable after Billroth H gastrectomy. Gastrectomy with Roux-en-Y anastomosis had no effect on gastric HP infection. KEY WORDS: Helicobacter pylori; peptic ulcer; partial gastrectomy.
Helicobacter pylori (HP) is present on the gastric mucosa of most patients with peptic ulcer, and a causal relationship has been suggested but is still unproven (1, 2). This causal relationship is based in part on the lower relapse rate of duodenal ulcer in Manuscript received April 26, 1990; revised manuscript received March l, i991; accepted March 7, 1991. From the Departments of Gastroenteroiogy-Hepatology and Pathology, University Hospital, Leiden; and Department of Surgery, Canisius-Wilhelmina Hospital, Nijmegen, The Netherlands. Address for reprint requests: Prof. Dr. C.B.H.W. Lamers, Dept. of Gastroenterology-Hepatology, Building 1, C4-P015, University Hospital, P.O. Box 9600, 2300 RC Leiden, The Netherlands.
patients cleared from the microorganism by antiulcer therapy using colloidal bismuth compounds (3). Partial gastrectomy is highly effective in healing peptic ulcer and preventing ulcer relapses (4). Furthermore, it has been reported that biliary enterogastric reflux eradicates gastric infection with HP (5, 6). In several studies of nonoperated patients, there was a very good correlation between gastric HP infection and the presence of serum antibodies against HP (7-il). In addition, medical eradication of HP from the stomach is accompanied by a decrease in HP antibodies (12, 13).
Digestive Diseases and Sciences, Vol. 36, No. 12 (December 1991)
0163-2116/91/1200-1697506.50/09 1991PlenumPublishingCorporation
1697
LAMERS ET AL We have analyzed in a prospective, randomized study the effect of gastrectomy with either Billroth II or Roux-en-Y anastomosis on serum IgG and IgA immunoglobulins against HP in patients with peptic ulcer having HP infection demonstrated in their preoperative endoscopic gastric biopsies. MATERIALS AND METHODS Seventeen patients with duodenal and five with gastric ulcer were studied before and at regular intervals for 24 months after a two-thirds to three-fourths distal gastrectomy. In random order, a Roux-en-Y diversion was Constructed in 1i patients (two females, nine males, mean age 51 --- 3 years), while the other 11 patients (three females, eight males, mean age 51 --- 4 years) underwent a Billroth II anastomosis. At surgery great care was taken to perform a gastric resection of similar extent in both groups. None of the patients was treated with bismuth compounds or antibiotics in the three months before and the 24 months after surgery. Endoscopy with biopsies taken from standardized sites was performed within two weeks before and at six months after surgery. Preoperatively, one biopsy from the antrum and one from the lesser and one from the greater curvature of the body were stained by the Warthin-Starry technique to facilitate the demonstration of CP. Postoperatively, one biopsy from the anastomosis and one from the lesser and one from the greater curvature were stained by this technique. The biopsies were also assessed by the gastritis activity score of Whitehead et al (14) and the reflux gastritis score of Dixon et al (15). Shortly before and at 10 days, and 6, !5, and 24 months postoperatively serum IgA antibodies (anti-HP IgA) and IgG antibodies (anti-HP IgG) against HP were measured by an ELISA technique, as described previously (11). All serum samples were measured in a single assay. Anti-HP IgA and anti-HP IgG were expressed as the absorbanCe index (AI) between the optical density of the patient's serum and a reference serum after subtraction of the blank readings .(I1, 14). Under the conditionS of the ELISA, ~is described previously (li), an absorbance index for antbHP IgA higher than 0.32 and for anti-HP IgG higher than 0.35 indicates gastric HP infection with a chance of m0re than 95% (11). Bile acids were measured in four consecutiye 15-rain fasting gastric aspiration samples by the Enzabile test (Nygaard & Co Diagnostics, Oslo). Fasting bile acid reflux was expressed in micromoles per hour. Results are expressed as mean -+ SEM or medians, as indicated. Statistical analysis was done by the Wilcoxon and chi-square tests. The study was approved by the local ethical committee. RESULTS HP was demonstrable in all preoperative gastric biopsies, both from the antrum and the body of the stomach. Preoperatively, anti-HP IgA was raised in 20 of 22 patients (range 0.21-1.69) and anti-HP IgG
1698
in all 22 patients (range 0.38-1.31). There were no differences in anti-HP titers between the five patients with gastric and 17 with duodenal ulcer. Median preoperative gastric bile acids were similar" for the Billroth II and Roux-en-Y patients (0.35 and 0.30 ~mol/hr). Preoperatively, there were no differences in gastritis score by either the Whitehead or the Dixon assessment between patients who ultimately underwent Billroth II or Roux-en-Y gastrectomy. At six months postoperatively HP was demonstrated in all patients with Roux-en-Y anastomosis, but could no longer be found in four of the Billroth II patients (P = 0,09). Median gastric bile acids were increased to 16.10 txmol/hr in the Billroth II patients (P < 0.01) but were decreased in the Roux-en-Y group to 0.10 ~mol/hr (P < 0.05). In the four Billroth II patients in whom no HP infection was demonstrable in postoperative biopsies, gastric bile acid reflux was not different from the results in the seven Billroth II patients without HP clearance. The four patients with Billroth II anastomosis, in whom HP was no longer demonstrable in gastric biopsies, had a rapid and pronounced decrease of anti-HP IgA followed by stabilization during the 24-month follow-up period (Figure 1; Table 1). The fall in anti-HP IgA levels in the Billroth II group as a whole was accounted for by the substantial fall in the four patients who became HP negative (Table 1). No change of anti-HP IgA was found in the seven patients with Billroth II gastrectomy with persistent HP infection (Figure 1; Table 1). Furthermore, no Significant change of anti-HP IgA was found in the patients with Roux-en-Y gastrectomy (Figure 1; Table 1). Anti-HP IgG showed variable results in the four patients with Billroth II gastrectomy without HP in the postoperative gastric biopsies (Figure 2; Table 2). No significant change of anti-HP IgG was observed in the patients with Billroth II gastrectomy with persistent HP infection and in those with Roux-en-Y anastomosis (Figure 2; Table 2). As shown in Figures 1 and 2, anti-HP-IgA normalized in patient 4 only (AI < 0.35), while anti-HP IgG was reduced to normal values only in patient 3 (AI < 0.32). Patient 4 was the only patient with a fourfold fall in anti-HP IgA after gastric surgery (Figure 1; Table 1). In patients 1 and 2 both anti-HP IgA and anti-HP IgG persisted to be supranormal despite apparent clearance of HP. Furthermore, in none of these four patients had gastritis activity diminished after Billroth II gastrectomy despite absence of HP in the gastric biopsies. HowDigestive Diseases and Sciences, Vol. 36, No. 12 (December 1991)
H. Pylori A N T I B O D I E S
AFTER
GASTRECTOMY
anti-HP-IgA (A.l.) 2
GASTRECTOMY
1.8
1
1.6 1.4 1.2
0~
1 0.8 0.6 Pt 1
0.4
Pt 3
0.2
Pt 4
0
I
I 10
Pre Days
I 6
I 15
I
Months
Months
24 Months
Fig 1. Effect of gastrectomy on serum anti-HP IgA in four Billroth II patients without H P in postoperative gastric biopsies (individual data denoted by small black squares), in seven patients with Billroth II anastomosis with persistent gastric H P infection (medians; cross symbols), and 11 patients with Roux-en-Y anastomosis with persistent H P infection (medians; triangles). A.I.: absorbance index.
ever, the four patients who cleared the microorganism had a higher reflux gastritis score at the site of the anastomosis but not in the gastric body than the patients who failed to clear the HP infection (P < 0.02). In the patients with persistent HP infection, there was no change of gastritis activity or reflux gastritis parameters. DISCUSSION This prospective randomized study on the effect of gastrectomy with either Roux-en-Y or Billroth II
anastomosis on HP serology showed that clearance of HP from the gastric mucosa is accompanied by a decrease in anti-HP IgA, while the effect on anti-HP IgG is rather variable. This decrease in anti-HP IgA was followed by stabilization for the 24-month follow-up period. The more consistent early response of anti-HP IgA as compared with anti-HP IgG in the patients without postoperative HP infection may be related in part to the shorter half-life of IgA in serum. Normalization was achieved in only one patient for anti-HP IgA and in another patient
TABLE 1. SERUM TITERS OF IgA ANTIBODIES AGAINST Helicobacter pylori (HP) BEFORE AND AT REGULAR INTERVALS AFTER PARTIAL GASTRECTOMY WITH BILLROTH II OR ROUX-EN-Y ANASTOMOSIS (MEAN • SEM)
Postoperative Preoperative Biilroth II gastrectomy (N = 11) H P absent in biopsies pt 1 2 3 4 Others (N = 7) Roux-en-Y gastrectomy (N = 11)
0.96 • 0.73 1.60 1.14 0.92 0.88 • 0.70 •
10 days
6 months
15 months
24 months
0.12
0.70 --- 0.18a*
0.66 --- 0.11b
0.67 --- 0.09b
0.71 --- 0.13b
0.16 0.13
0.44 0.82 0.38 0.22 0.86 0.55 •
0.55 1.18 0.40 0.19 0.72 --- 0.13 0.61 • 0.12a
0.47 1.18 0.39 0.32 0.71 -+ 0.11 0.64 • 0.11
0.51 1.40 0.38 0.15 0.77 --- 0.23 0.59 • 0.08
0.21 0.11a
*a, P < 0.05; b, P < 0.01 compared to preoperative level. Digestive Diseases and Sciences, Vol. 36, No. 12 (December 1991)
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LAMERS ET AL anti-HP-IgG (A.I.)
1
GASTRECTOMY
1 0.8
Pt 1 Pt 2 0.6
pt 4
0.4
1
/
=
~ "~ P t 3
0.2
0
I
Pre
I
I
I
I
10 Days
6 Months
15 Months
24 Months
Fig 2. Effect o f gastrectomy on serum anti-HP IgG in four Billroth II patients without H P in postoperative gastric biopsies (individual data denoted by small black squares), in seven patients with Billroth II anastomosis with persistent gastric HP infection (median; cross symbols), and 11 patients with Roux-en-Y anastomosis with persistent H P infection (median; triangles), A.I.: absorbance index.
for anti-HP IgG, while in the two other patients without HP in postoperative biopsies both anti-HP IgA and anti-HP IgG levels continued to be supranormal. This finding may suggest that following the Billroth II gastrectomy the gastric HP infection was not fully eradicated and that there was persistent patchy colonization of the gastric remnant with HP in these patients. It is unlikely that the decrease in anti-HP IgA is merely the result of the reduction of
the antigenic load by the gastrectomy, because such marked decreases in anti-HP IgA were not discernible in the patients with Roux-en-Y anastomosis in whom a gastrectomy of similar size had been performed. Furthermore, anti-HP IgA did not show such pronounced changed in those patients with Billroth II gastrectomy in whom HP was still demonstrated after gastrectomy. In addition, in the patients without HP infection the microorganism
TABLE 2. SERUM TITERS OF IgG ANTIBODIES AGAINST Helicobacter pylori (HP) BEFORE AND AT REGULAR INTERVALS AFTER PARTIAL GASTRECTOMY WITH BILLROTH II OR ROUX-EN-Y ANASTOMOSIS Postoperative
Billroth II gastrectomy (N = 11) HP absent in biopsies pt 1 2 3 4 Others (N = 7) R o u x - e n - Y g a s t r e c t o m y ( N = 11)
Preoperative
10 days
6 months
0.69 -+ 0.06
0.65 _-x- 0.06
0.63 -
0.39 0.79 0.72 0.85 0.69 -+ 0.08 0.70 --- 0.08
0.29 0.79 0.34 0.87 0.65 --- 0.07 0.67 -4- 0.09
0.58 0.81 0.34 0.58 0.66 -+ 0.08 0.65 --. 0.07
0.06
15 months
24 months
0.66 --- 0.06
0.60 +-- 0.05*
0.72 0.86 0.32 0.85 0.64 --- 0.08* 0.66 -+ 0.06
0.72 0.69 0.29 0.53 0.62 --- 0.07 0.62 --- 0.06
*P < 0.05 compared to preoperative level.
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Digestive Diseases and Sciences, Vol. 36, No. 12 (December 1991)
H. Pylori ANTIBODIES A F T E R GASTRECTOMY
had in fact been demonstrated in biopsies of the gastric body mucosa preoperatively, pointing to an effect of the Billroth II gastrectomy on the gastric body. Interestingly, the four patients in whom no HP was detectable postoperatively had undergone Billroth II gastrectomy, whereas all patients with Roux-en-Y gastrectomy had the microorganism detectable in postoperative biopsies. Since the main difference between the two types of anastomosis is the presence of marked biliary enterogastric reflux after Billroth II surgery, as confirmed in the present study, it is likely that eradication of HP is secondary to this so-called biliary or alkaline reflux (1, 2). This suggestion is supported by a recent study showing that diversion of biliary reflux from the stomach by Roux-en-Y anastomosis in 24 patients with symptomatic bile reflux was followed by an increase in HP-positive biopsies from 54% to 92% (17). It is unlikely that the effect of Billroth II gastrectomy on HP colonization is due to the gastric acid-lowering effect of gastrectomy, because treatment of peptic ulcer patients with the gastric antisecretory drugs ranitidine and omeprazole does not affect serum anti-HP IgA and anti-HP IgG levels (unpublished observation). The finding that after Billroth II gastrectomy HP was apparently eradicated in only four (36%) of the patients is in line with a recent study of 108 patients with Billroth I or BiUroth II gastrectomy, in whom the microorganism was present in about half of them (18). ACKNOWLEDGMENTS
The authors are indebted to Louise Niepoth and Nelia Koek-van Beelen for secretarial assistance.
REFERENCES 1. Goodwin CS: Duodenal ulcer, Campylobacter pylori, and the "leaking roof" concept. Lancet 2:1467-1469, 1988 2. Graham DY: Campylobacterpylori and peptic ulcer disease. Gastroenterology 96:615-625, 1989 3. Marshall BJ, Goodwin CS, Warren JR, et al: Prospective double-blind trial of duodenal ulcer relapse after eradication of Campylobacter pylori. Lancet 2:1437-1441, 1988
Digestive Diseases and Sciences, Vol. 36, No. 12 (December1991)
4. Thompson JC, Wiener I: Evaluation of surgical treatment of duodenal: Short- and long-term effects. Clin Gastroenterol 13:569-600, 1984 5. O'Connor HJ, Wyatt JI, Dixon MF, Axon ATR: Campylobacter-like organisms and reflux gastritis. J Clin Pathol 39:531-534, 1986 6. O'Connor HJ, Dixon MF, Wyatt JI, et al: Effect of duodenal ulcer surgery and enterogastric reflux on Campylobacter pyloridis. Lancet 2:1178-1181, 1986 7. Faisal MA, Santogade PJ, Bakkenheuser V, Scholes JV, Holt PR, Kotler DP: Sensitivity and specificity of the serologic diagnosis of Campylobacter pylori infection. Gastroenterology 94:A121, 1988 8. Goodwin CS, Blincow E, Peterson G, et al: Enzyme-linked immunosorbentassay for Campylobacter pyloridis: Correlation with presence of C. pyloridis in the gastric mucosa. J Infect Dis 155:488-494, 1987 9. Martin DF, Montgomery E, Dobek AS, Patrissi GA, Peura DA: Noninvasive detection of histologic gastritis. Gastroenterology 94:A285, 1988 10. Perez-Perez GI, Dworkin BM, Chodos JE, Blaser MJ: Campylobacter pylori antibodies in humans. Ann Intern Med 109:11, 1988 11. Pena AS, Endtz HP: Offerhaus GJA, et al: The value of serology (ELISA and immunoblotting) for the diagnosis of Campylobacter pylori infection. Digestion 44:131-141, 1989 12. Vaira D, Holton J, Falzon M, et al: Serum antibody titres before and after therapy in patients with Campylobacter associated gastritis. Gut 29:A709, 1988 13. Oderda G, Holton J, Altare F, Vaira D, Ainley C, Ansaldi N: Amoxycillin plus tinidazole for Campylobacter pylori gastritis in children: Assessment by serum IgG antibody, pepsinogen I, and gastrin levels. Lancet 1:690-692, 1989 14. Whitehead R, Truelove SC, Gear MWL: The histological diagnosis of chronic gastritis in fibreoptic gastroscope biopsy specimens. J Clin Pathol 25:1-11, 1972 15. Dixon MF, O'Connor HJ, Axon ATR, King RFGJ, Johnston D: Reflux gastritis: Distinct histopathological entity? J Clin Pathol 39:524-530, 1986 16. Voller A, Bidwell DE, Bartlett A: The enzyme linked immunosorbent assay (ELISA): A guide with abstracts of microplate applications. Dynatech Europe, Borough House, Guernsey, 1979 17. O'Connor HJ, Newbold KN, Alexander-Williams J, Thompson H, Drnmm J, Donovan IA: Effect of Roux-en-Y biliary diversion on Campylobacter pylori. Gastroenterology 97:958-964, 1989 18. Loffeld RJLF, Loffeld BCA, Arends JW, Flendrig JA, van Spreeuwel JP: Retrospective study of Campylobacter-like organisms in patients undergoing partial gastrectomy. J Clin Pathol 41:1313-1315, 1988
1701
Effect of Partial Gastrectomy on Serum Anti-Helicobacter pylori Immunoglobulins in Peptic Ulcer Patients CORNELIS B.H.W. LAMERS, PAUL N.M.A. RIEU, ROELAND A. VEENENDAAL, WlM VAN DUIJN, G. JOHAN A. OFFERHAUS, HARRY J.M. JOOSTEN, and A. SALVADOR PElqA
Since biliary enterogastric reflux is suggested to eradicate gastric infection with Heiicobacter pylori (HP), we have investigated in a prospective randomized study the effect o f partial gastrectomy with either Billroth H or Roux-en- Y anastomosis on infection with HP as assessed by the titers o f lgG and IgA antibodies against HP in serum. These antibodies were measured by ELISA in serum of 22 patients before and at 10 days and 6, 15, and 24 months after either Billroth H (N = 11) or Roux-en-Y (N = 11) gastrectomy for peptic ulcer. All patients had HP demonstrated in their preoperative endoscopic gastric biopsies, The preoperative serum IgA antibodies against HP (anti-HP IgA) were increased in 20 o f the 22 patients (range 0.21-1.69) while the IgG antibodies (anti-HP IgG) were increased in all 22 patients (range 0.38-1,31). Four o f the Billroth H patients had clearance o f liP from gastric biopsies accompanied by rapid and pronounced decrease o f anti-HP IgA. In contrast, the patients with Roux-en-Y gastrectomy and the Billroth H patients with persistent HP infection had no change in anti-HP IgA after surgery. Anti-HP IgG showed variable results in the four patients without gastric HP infection and was not affected by gastrectomy in the patients with persistent HP infection. We concluded that serum anti-HP IgA, but not anti-HP IgG, is helpful in identifying those patients in whom HP is no longer demonstrable after Billroth H gastrectomy. Gastrectomy with Roux-en-Y anastomosis had no effect on gastric HP infection. KEY WORDS: Helicobacter pylori; peptic ulcer; partial gastrectomy.
Helicobacter pylori (HP) is present on the gastric mucosa of most patients with peptic ulcer, and a causal relationship has been suggested but is still unproven (1, 2). This causal relationship is based in part on the lower relapse rate of duodenal ulcer in Manuscript received April 26, 1990; revised manuscript received March l, i991; accepted March 7, 1991. From the Departments of Gastroenteroiogy-Hepatology and Pathology, University Hospital, Leiden; and Department of Surgery, Canisius-Wilhelmina Hospital, Nijmegen, The Netherlands. Address for reprint requests: Prof. Dr. C.B.H.W. Lamers, Dept. of Gastroenterology-Hepatology, Building 1, C4-P015, University Hospital, P.O. Box 9600, 2300 RC Leiden, The Netherlands.
patients cleared from the microorganism by antiulcer therapy using colloidal bismuth compounds (3). Partial gastrectomy is highly effective in healing peptic ulcer and preventing ulcer relapses (4). Furthermore, it has been reported that biliary enterogastric reflux eradicates gastric infection with HP (5, 6). In several studies of nonoperated patients, there was a very good correlation between gastric HP infection and the presence of serum antibodies against HP (7-il). In addition, medical eradication of HP from the stomach is accompanied by a decrease in HP antibodies (12, 13).
Digestive Diseases and Sciences, Vol. 36, No. 12 (December 1991)
0163-2116/91/1200-1697506.50/09 1991PlenumPublishingCorporation
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LAMERS ET AL We have analyzed in a prospective, randomized study the effect of gastrectomy with either Billroth II or Roux-en-Y anastomosis on serum IgG and IgA immunoglobulins against HP in patients with peptic ulcer having HP infection demonstrated in their preoperative endoscopic gastric biopsies. MATERIALS AND METHODS Seventeen patients with duodenal and five with gastric ulcer were studied before and at regular intervals for 24 months after a two-thirds to three-fourths distal gastrectomy. In random order, a Roux-en-Y diversion was Constructed in 1i patients (two females, nine males, mean age 51 --- 3 years), while the other 11 patients (three females, eight males, mean age 51 --- 4 years) underwent a Billroth II anastomosis. At surgery great care was taken to perform a gastric resection of similar extent in both groups. None of the patients was treated with bismuth compounds or antibiotics in the three months before and the 24 months after surgery. Endoscopy with biopsies taken from standardized sites was performed within two weeks before and at six months after surgery. Preoperatively, one biopsy from the antrum and one from the lesser and one from the greater curvature of the body were stained by the Warthin-Starry technique to facilitate the demonstration of CP. Postoperatively, one biopsy from the anastomosis and one from the lesser and one from the greater curvature were stained by this technique. The biopsies were also assessed by the gastritis activity score of Whitehead et al (14) and the reflux gastritis score of Dixon et al (15). Shortly before and at 10 days, and 6, !5, and 24 months postoperatively serum IgA antibodies (anti-HP IgA) and IgG antibodies (anti-HP IgG) against HP were measured by an ELISA technique, as described previously (11). All serum samples were measured in a single assay. Anti-HP IgA and anti-HP IgG were expressed as the absorbanCe index (AI) between the optical density of the patient's serum and a reference serum after subtraction of the blank readings .(I1, 14). Under the conditionS of the ELISA, ~is described previously (li), an absorbance index for antbHP IgA higher than 0.32 and for anti-HP IgG higher than 0.35 indicates gastric HP infection with a chance of m0re than 95% (11). Bile acids were measured in four consecutiye 15-rain fasting gastric aspiration samples by the Enzabile test (Nygaard & Co Diagnostics, Oslo). Fasting bile acid reflux was expressed in micromoles per hour. Results are expressed as mean -+ SEM or medians, as indicated. Statistical analysis was done by the Wilcoxon and chi-square tests. The study was approved by the local ethical committee. RESULTS HP was demonstrable in all preoperative gastric biopsies, both from the antrum and the body of the stomach. Preoperatively, anti-HP IgA was raised in 20 of 22 patients (range 0.21-1.69) and anti-HP IgG
1698
in all 22 patients (range 0.38-1.31). There were no differences in anti-HP titers between the five patients with gastric and 17 with duodenal ulcer. Median preoperative gastric bile acids were similar" for the Billroth II and Roux-en-Y patients (0.35 and 0.30 ~mol/hr). Preoperatively, there were no differences in gastritis score by either the Whitehead or the Dixon assessment between patients who ultimately underwent Billroth II or Roux-en-Y gastrectomy. At six months postoperatively HP was demonstrated in all patients with Roux-en-Y anastomosis, but could no longer be found in four of the Billroth II patients (P = 0,09). Median gastric bile acids were increased to 16.10 txmol/hr in the Billroth II patients (P < 0.01) but were decreased in the Roux-en-Y group to 0.10 ~mol/hr (P < 0.05). In the four Billroth II patients in whom no HP infection was demonstrable in postoperative biopsies, gastric bile acid reflux was not different from the results in the seven Billroth II patients without HP clearance. The four patients with Billroth II anastomosis, in whom HP was no longer demonstrable in gastric biopsies, had a rapid and pronounced decrease of anti-HP IgA followed by stabilization during the 24-month follow-up period (Figure 1; Table 1). The fall in anti-HP IgA levels in the Billroth II group as a whole was accounted for by the substantial fall in the four patients who became HP negative (Table 1). No change of anti-HP IgA was found in the seven patients with Billroth II gastrectomy with persistent HP infection (Figure 1; Table 1). Furthermore, no Significant change of anti-HP IgA was found in the patients with Roux-en-Y gastrectomy (Figure 1; Table 1). Anti-HP IgG showed variable results in the four patients with Billroth II gastrectomy without HP in the postoperative gastric biopsies (Figure 2; Table 2). No significant change of anti-HP IgG was observed in the patients with Billroth II gastrectomy with persistent HP infection and in those with Roux-en-Y anastomosis (Figure 2; Table 2). As shown in Figures 1 and 2, anti-HP-IgA normalized in patient 4 only (AI < 0.35), while anti-HP IgG was reduced to normal values only in patient 3 (AI < 0.32). Patient 4 was the only patient with a fourfold fall in anti-HP IgA after gastric surgery (Figure 1; Table 1). In patients 1 and 2 both anti-HP IgA and anti-HP IgG persisted to be supranormal despite apparent clearance of HP. Furthermore, in none of these four patients had gastritis activity diminished after Billroth II gastrectomy despite absence of HP in the gastric biopsies. HowDigestive Diseases and Sciences, Vol. 36, No. 12 (December 1991)
H. Pylori A N T I B O D I E S
AFTER
GASTRECTOMY
anti-HP-IgA (A.l.) 2
GASTRECTOMY
1.8
1
1.6 1.4 1.2
0~
1 0.8 0.6 Pt 1
0.4
Pt 3
0.2
Pt 4
0
I
I 10
Pre Days
I 6
I 15
I
Months
Months
24 Months
Fig 1. Effect of gastrectomy on serum anti-HP IgA in four Billroth II patients without H P in postoperative gastric biopsies (individual data denoted by small black squares), in seven patients with Billroth II anastomosis with persistent gastric H P infection (medians; cross symbols), and 11 patients with Roux-en-Y anastomosis with persistent H P infection (medians; triangles). A.I.: absorbance index.
ever, the four patients who cleared the microorganism had a higher reflux gastritis score at the site of the anastomosis but not in the gastric body than the patients who failed to clear the HP infection (P < 0.02). In the patients with persistent HP infection, there was no change of gastritis activity or reflux gastritis parameters. DISCUSSION This prospective randomized study on the effect of gastrectomy with either Roux-en-Y or Billroth II
anastomosis on HP serology showed that clearance of HP from the gastric mucosa is accompanied by a decrease in anti-HP IgA, while the effect on anti-HP IgG is rather variable. This decrease in anti-HP IgA was followed by stabilization for the 24-month follow-up period. The more consistent early response of anti-HP IgA as compared with anti-HP IgG in the patients without postoperative HP infection may be related in part to the shorter half-life of IgA in serum. Normalization was achieved in only one patient for anti-HP IgA and in another patient
TABLE 1. SERUM TITERS OF IgA ANTIBODIES AGAINST Helicobacter pylori (HP) BEFORE AND AT REGULAR INTERVALS AFTER PARTIAL GASTRECTOMY WITH BILLROTH II OR ROUX-EN-Y ANASTOMOSIS (MEAN • SEM)
Postoperative Preoperative Biilroth II gastrectomy (N = 11) H P absent in biopsies pt 1 2 3 4 Others (N = 7) Roux-en-Y gastrectomy (N = 11)
0.96 • 0.73 1.60 1.14 0.92 0.88 • 0.70 •
10 days
6 months
15 months
24 months
0.12
0.70 --- 0.18a*
0.66 --- 0.11b
0.67 --- 0.09b
0.71 --- 0.13b
0.16 0.13
0.44 0.82 0.38 0.22 0.86 0.55 •
0.55 1.18 0.40 0.19 0.72 --- 0.13 0.61 • 0.12a
0.47 1.18 0.39 0.32 0.71 -+ 0.11 0.64 • 0.11
0.51 1.40 0.38 0.15 0.77 --- 0.23 0.59 • 0.08
0.21 0.11a
*a, P < 0.05; b, P < 0.01 compared to preoperative level. Digestive Diseases and Sciences, Vol. 36, No. 12 (December 1991)
1699
LAMERS ET AL anti-HP-IgG (A.I.)
1
GASTRECTOMY
1 0.8
Pt 1 Pt 2 0.6
pt 4
0.4
1
/
=
~ "~ P t 3
0.2
0
I
Pre
I
I
I
I
10 Days
6 Months
15 Months
24 Months
Fig 2. Effect o f gastrectomy on serum anti-HP IgG in four Billroth II patients without H P in postoperative gastric biopsies (individual data denoted by small black squares), in seven patients with Billroth II anastomosis with persistent gastric HP infection (median; cross symbols), and 11 patients with Roux-en-Y anastomosis with persistent H P infection (median; triangles), A.I.: absorbance index.
for anti-HP IgG, while in the two other patients without HP in postoperative biopsies both anti-HP IgA and anti-HP IgG levels continued to be supranormal. This finding may suggest that following the Billroth II gastrectomy the gastric HP infection was not fully eradicated and that there was persistent patchy colonization of the gastric remnant with HP in these patients. It is unlikely that the decrease in anti-HP IgA is merely the result of the reduction of
the antigenic load by the gastrectomy, because such marked decreases in anti-HP IgA were not discernible in the patients with Roux-en-Y anastomosis in whom a gastrectomy of similar size had been performed. Furthermore, anti-HP IgA did not show such pronounced changed in those patients with Billroth II gastrectomy in whom HP was still demonstrated after gastrectomy. In addition, in the patients without HP infection the microorganism
TABLE 2. SERUM TITERS OF IgG ANTIBODIES AGAINST Helicobacter pylori (HP) BEFORE AND AT REGULAR INTERVALS AFTER PARTIAL GASTRECTOMY WITH BILLROTH II OR ROUX-EN-Y ANASTOMOSIS Postoperative
Billroth II gastrectomy (N = 11) HP absent in biopsies pt 1 2 3 4 Others (N = 7) R o u x - e n - Y g a s t r e c t o m y ( N = 11)
Preoperative
10 days
6 months
0.69 -+ 0.06
0.65 _-x- 0.06
0.63 -
0.39 0.79 0.72 0.85 0.69 -+ 0.08 0.70 --- 0.08
0.29 0.79 0.34 0.87 0.65 --- 0.07 0.67 -4- 0.09
0.58 0.81 0.34 0.58 0.66 -+ 0.08 0.65 --. 0.07
0.06
15 months
24 months
0.66 --- 0.06
0.60 +-- 0.05*
0.72 0.86 0.32 0.85 0.64 --- 0.08* 0.66 -+ 0.06
0.72 0.69 0.29 0.53 0.62 --- 0.07 0.62 --- 0.06
*P < 0.05 compared to preoperative level.
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H. Pylori ANTIBODIES A F T E R GASTRECTOMY
had in fact been demonstrated in biopsies of the gastric body mucosa preoperatively, pointing to an effect of the Billroth II gastrectomy on the gastric body. Interestingly, the four patients in whom no HP was detectable postoperatively had undergone Billroth II gastrectomy, whereas all patients with Roux-en-Y gastrectomy had the microorganism detectable in postoperative biopsies. Since the main difference between the two types of anastomosis is the presence of marked biliary enterogastric reflux after Billroth II surgery, as confirmed in the present study, it is likely that eradication of HP is secondary to this so-called biliary or alkaline reflux (1, 2). This suggestion is supported by a recent study showing that diversion of biliary reflux from the stomach by Roux-en-Y anastomosis in 24 patients with symptomatic bile reflux was followed by an increase in HP-positive biopsies from 54% to 92% (17). It is unlikely that the effect of Billroth II gastrectomy on HP colonization is due to the gastric acid-lowering effect of gastrectomy, because treatment of peptic ulcer patients with the gastric antisecretory drugs ranitidine and omeprazole does not affect serum anti-HP IgA and anti-HP IgG levels (unpublished observation). The finding that after Billroth II gastrectomy HP was apparently eradicated in only four (36%) of the patients is in line with a recent study of 108 patients with Billroth I or BiUroth II gastrectomy, in whom the microorganism was present in about half of them (18). ACKNOWLEDGMENTS
The authors are indebted to Louise Niepoth and Nelia Koek-van Beelen for secretarial assistance.
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