In the late 1980s, acquisition of intramucosal lymph follicles and accumulation of immunoglobulin A producing plasma cells were found to result from H pylori
infection of the gastric mucosa.1,2,17
This acquired lymphatic tissue showed morphological characteristics of MALT and regressed after successful eradication of the bacterium.18
In 1991, Wotherspoon and colleagues3
for the first time demonstrated that patients with primary gastric MALT lymphoma are regularly infected by H pylori
. Since then, this finding has been confirmed by other investigators.4,18,19
In addition to histomorphological studies, recent epidemiological,5,6
data clearly indicate that H pylori
plays a decisive role in the development and progression of gastric MALT lymphoma. This convincing evidence inevitably involved a therapeutic effort. In 1993, Wotherspoon and colleagues20
reported complete regression of low grade lymphoma following successful H pylori
eradication in five of six cases. Prospective trials have confirmed this observation21–26
and reported rates of complete regression of lymphoma varying between 56% and 100%.
Undoubtedly, eradication of H pylori
represents a fascinating therapeutic option because of both its simplicity and efficacy. However, data on long term outcome are currently rare. To our knowledge, our series is one of the largest prospective studies on H pylori
eradication therapy in gastric MALT lymphoma, and with a median follow up of more than four years comprises one of the longest observation periods. In 1999, Isaacson described a six year follow up of the first six patients who were successfully treated by H pylori
Although transient histological or molecular relapse has been observed in some patients, prolonged disease free remission was documented in all patients with or without molecular evidence of a monoclonal B cell population. The overall complete lymphoma regression rate in our study of 62.5% does not differ considerably from studies with a shorter follow up.21–26
Assessment of the depth of lymphoma infiltration by endoscopy and EUS has thus far been shown to have predictive value.23,26,28–30
However, the findings reported in these studies vary widely. While Ruskoné-Fourmestraux et al
describe complete remission rates as high as 79% in lymphomas infiltrating the mucosa only,28
Steinbach et al
achieved complete remission in stage 1 patients of no more than 56%.26
What are the possible explanations for these discrepancies? It has to be kept in mind that the diagnostic accuracy of EUS in the local staging of gastric lymphoma is limited. We found that EUS correctly identified only 53% of patients compared with the gold standard of pathohistological stage of the resected specimen.31
This was a multicentre study, thus probably reflecting the situation in a more realistic way than results from highly specialised gastroenterology units.28,30
Finally, experience with EUS was limited at the time this study started. We strongly believe that with increasing experience of endoscopists and technical improvements such as the use of small ultrasound probes (mini-echoendoscopes) and ultrasound guided biopsy facilities, EUS as a predictive factor of lymphoma remission will become substantially more accurate. Considering the diagnostic uncertainty on the one hand and possible regression of lymphoma even in locally more advanced stages, we would not at present exclude patients with infiltration of the submucosa or muscularis propria from eradication therapy. However, they may need a more intensive follow up.
Relapse was found in four patients, one of whom had a high grade lymphoma. In view of the comparatively short time period (six months) until relapse recurred in the latter patient, it remains a matter of speculation whether this was in fact recurrence or previously undiagnosed high malignant foci of the initial lymphoma. According to our experience in 266 patients with primary gastric B cell lymphoma, approximately 18% reveal synchronous low grade and high grade components.24
The fact that high grade lymphoma was found in only three patients (fig 1) allows two conclusions to be drawn. Firstly, the risk of high malignant transformation in patients treated by exclusive H pylori
eradication appears to be low. Secondly, a subtle endoscopic-bioptic technique (gastric mapping), as performed here, minimises sampling errors.
With respect to both the rate of relapse and H pylori
reinfection, our data are very similar to those reported by Neubauer and colleagues.25
In their prospective series of 50 patients, they observed four cases of local recurrence, only one being accompanied by H pylori
reinfection. Another patient developed a high grade nasal lymphoma. This study offers another highly interesting aspect. In 22 of 31 patients (71%) with continuous complete remission, monoclonal B cells persisted. The biological significance of these cells is not clear at present.
Eighteen per cent of patients studied were characterised by normalised endoscopic and endosonographic findings but persistent lymphoma infiltrates (minimal residual disease). Despite well established criteria to refer such patients to surgery or radiotherapy, we decided on a watch and wait strategy after extensive and repeated information from the patients. Our findings that they did well during further follow up, focus on a possibly favourable natural course of minimal residuals of low grade gastric MALT type lymphoma after successful eradication of H pylori
. Molecular analyses were beyond the scope of this multicentre study. With respect to translocation t(11;18), discordant results have been published recently.32–35
There is some evidence that t(11;18) positive lymphoma are characterised by a more advanced tumour stage and failure to respond to H pylori
On the other hand, t(11;18) negative lymphoma reveal more clonal aberrations and are prone to progress more frequently to high grade lymphoma.34
In a small series, we have shown that minimal residuals of low grade gastric MALT type lymphoma patients being t(11;18) positive may have a favourable course of disease.35
Hence a watch and wait strategy may become an option in such a situation.
In summary, H pylori eradication is an effective treatment modality in gastric marginal zone B cell lymphoma of MALT. The majority of patients treated exclusively in this way have a favourable long term outcome, offering a real chance of cure.