Table 9.
Comparison of antisecretory treatment results in patients with or without VB12 deficiency.
| Number (% Total Group) | |||
|---|---|---|---|
| VB12 Deficiency | p-Value | ||
| Yes | No | ||
| Characteristic | (n = 37) | (n = 138) | |
| I. Type antisecretory treatment | |||
| # Previous gastric acid-reducing surgery (a) | 2 (5.4%) | 9 (6.5%) | 0.99 |
| Medical treatment: | 37 (100%) | 138 (100%) | |
| At the time of the present study | |||
| H2R (n = 9) | 0 (0%) | 9 (7%) | 0.21 |
| PPI (n = 166) | 37 (100%) | 129 (93%) | |
| During 10 yrs. prior to the present study | |||
| H2R only (n = 6) | 0 (0%) | 6 (4.3%) | 0.34 |
| PPI only (n = 150) | 34 (92%) | 116 (84%) | 0.72 |
| Any PPI (n = 166) | 37 (100% | 129 (93%) | 0.21 |
| H2R 1st then PPI (n = 17) (b) | 3(8.1%) | 15 (11%) | 0.99 |
| PPI > 5 yrs. (n = 93) | 25 (68%) | 68 (49%) | 0.063 |
| II. General medical/surgical acid treatment features | |||
| Age at 1st medical treatment (yrs.) | 43.9 ± 2.0 | 43.6 ± 1.0 | 0.88 |
| Age at H2R initial treatment (yrs.) | 41.7 ± 2.6 | 43.2 ± 1.0 | 0.54 |
| Age at PPI initial treatment (yrs.) | 48.0 ± 2.0 | 47.6 ± 1.0 | 0.88 |
| III. Duration of antisecretory Tx (yrs.) (mean ± SEM) | |||
| ZES onset to any acid Tx (n = 175) (a) | 3.8 ± 0.9 | 3.7 ± 0.4 | 0.92 |
| ZES onset to PPI started (n = 167) (a) | 7.6 ± 1.2 | 7.9 ± 0.6 | 0.76 |
| Initial acid treatment to the present study (n = 175) | 10.2 ± 1.0 | 10.1 ± 0.6 | 0.76 |
| Initial H2R treatment to PPI Tx (Tx PPI/H2R) (n = 124) | 6.0 ± 1.1 | 5.9 ± 0.5 | 0.96 |
| PPI Tx (+/− with H2R) prior to present study (all PPI) (n = 169) | 6.2 ± 0.6 | 5.5 ± 0.3 | 0.22 |
| Time treated only with H2R prior to present study (n = 6) | 0 | 15.0 ± 1.6 | 0.0022 |
| Time treated only with PPI prior to the present study (n = 45) | 3.2 ± 0.6 | 3.4 ± 0.5 | 0.73 |
| IV. Gastric acid control and VB12 status | |||
| IV.A. Correlations with present study for single admission results (n = 175) | |||
| Control acid output (mEq/h) (c) | |||
| mean ± SEM | 0.14 ± 0.04 | 1.71 ± 0.17 | <0.0001 |
| (range) | (0–1.10) | (0–9.5) | |
| Control acid pH | |||
| mean ± SEM | 6.4 ± 0.0.2 | 3.7 ± 0.2 | <0.0001 |
| (range) | (4.0–7.6) | (1.2–7.5) | |
| Number with control acid with pH < 3.5 (d) | 0 (0%) | 78 (56%) | <0.0001 |
| Number with control acid with pH ≥ 7 | 18(49%) | 12 (8.5%) | <0.0001 |
| IV.B. Correlation with acid control results for all admissions over previous 5 yrs. (n = 873) | |||
| With sustained achlorhydria (>50% Adm acid = 0) (e) | 27 (73%) | 33 (24%) | <0.0001 |
| With sustained hypochlorhydria (0.1 to <1 mEq/h (>50%) (e) | 10(27%) | 37(27%) | 0.99 |
| With >50% acid controls ≥1 mEq/h (e) | 0 (0%) | 68 (49%) | 0.0005 |
Abbreviations: Adm—admission; BAO—Basal acid output; MAO—Maximal acid output; FSG—serum fasting gastrin; and Tx—treatment. For other abbreviations, see legends in Table 1, Table 2, Table 3, Table 4, Table 5, Table 6, Table 7 and Table 8. (a) See legends in Table 1 and Table 2 for an explanation of each of these characteristics. (b) In the NIH perspective trials [106,214], H2Rs were the first effective acid antisecretory medical therapy, with cimetidine first used in 1978, ranitidine in 1982, and famotidine in 1983 [198,226,227]. PPIs were first used in 1983 with omeprazole and then with lansoprazole in 1989 [106,197,220,228]; so, all patients initially enrolled in this study were first treated with H2Rs (cimetidine, ranitidine, and famotidine) and later, most of them switched to PPIs (omeprazole and lansoprazole), while new patients generally started treatment with PPIs [106,229]. (c) All antisecretory drug doses were determined as described previously based on the results of the acid control secretory rate [104,106,164,227]. This was determined by assessing the drug acid control secretory rate for the hour prior to the next antisecretory dose, and the antisecretory dose was adjusted to control the acid hypersecretion to <10 mEq/h in the majority of patients [104,106,164,227] or to below <5 mEq/h in patients with moderate/severe GERD [103,166] or previous Billroth resections depending on UGI endoscopic findings and symptom control [166,222]. These levels have been shown to result in the healing of mucosal lesions and, if maintained, prevent the development of additional peptic mucosal damage [164,177,222,226]. (d) The frequency of gastric acid > pH 3.5 was included because studies reported that pepsin activation, which cleaves food-bound VB12 during digestion and is essential for VB12 absorption, is inhibited at pH levels > 3.5 [79,243]. (e) Using the 873 gastric acid drug control analysis performed over the 5 years of this study (19967–2001), the patients were divided into one of three acid control categories: the presence of sustained achlorhydria (>50% admission acid control = 0), sustained hypochlorhydria (acid control levels from 0.1 to <1 mEq/h > 50%), and >50% acid controls ≥1 mEq/h. This categorization was determined as described in the Methods section and previous studies [54,106,244].