We read with great interest the article by Whiting et al (Gut 2002;50:378–81). The Birmingham experience shows how the prevalence of gastric cancers detected at an early stage is significantly higher in the endoscopically surveyed population than in non-surveyed patients. As a result, this study demonstrates that, in the secondary prevention of gastric malignancy, the “once in a lifetime” strategy (suggested for colorectal cancer) is not cost effective while repeated endoscopies (in selected patients) seem most appropriate. This conclusion however raises two cardinal questions. Firstly, are there “special” requirements (that is, a protocol of gastric biopsy sampling) to be satisfied when carrying out the upper endoscopy procedure? Secondly, are there evidence based criteria for selecting patients to be included in surveillance programmes?
The authors do not provide detailed information on the number of biopsy samples obtained per endoscopy. We belive that a standardised protocol of biopsy sampling is a leading part of any upper endoscopy procedure, and mucosal “abnormalities” should be considered the targets of additional sampling.1 Taking into account that 46% of the cancers referred to in Whiting’s study were discovered within 13 months from the second last procedure, we agree with the authors who considered these cancers endoscopically missed.
The second point of concern is the rationale for a surveillance protocol. Any cost effective strategy of secondary cancer prevention requires the risk of cancer to be higher within subjects undergoing surveillance than in the general population. In the Birmingham study, such a prerequisite does not seem to have been assumed in the study design. Endoscopy surveillance definitively included the whole spectrum of abnormalities described in gastric carcinogenesis,2,3 from regenerative changes (with a nearly null cancer risk) to non-invasive neoplasia (which carries, by definition, predisposition for progression to invasion and metastasis). As a consequence of (i) cancers missed at endoscopy and (ii) shortness of the follow up period, the results shown in their table 3 may be misleading. The association of intestinal metaplasia (regardless of its histochemical phenotype) with the highest risk of cancer evolution is not only biologically questionable but, and this is even worse, it may result in inappropriate patient management. While intestinal metaplasia represents the most common background of stomach cancer,4,5 “gastric intestinalisation” per se does not carry the phenotypic and genotypic alterations pre-currying invasive neoplasm. Most importantly, the high prevalence of metaplastic lesions within subjects who will never develop adenocarcinoma exclude (non-extensive) intestinal metaplasia as the proper target of surveillance programmes.
In the natural history of epithelial tumours, the term dysplasia identifies a lesion that carries biological alterations comparable with those of full fledged cancer but lacking stromal invasion.2 Recently, the term “dysplasia” has been replaced by “non-invasive neoplasia”, which more clearly identifies such a lesion as the most advanced alteration antecedent to invasive adenocarcinoma.6 Since 1985, we have prospectively followed up a series of patients with low and high grade gastric non-invasive neoplasia.4 The follow up schedule was differentiated a priori, depending on the cancer risk presumably associated with each grade of lesion.7 The number of patients enrolled in each diagnostic category, follow up time, and number of cancers detected are shown in table 1▶. It is worth emphasising the high prevalence of early gastric cancers (77%) among the 30 cases of cancer detected in our prospective follow up study. The 19 cases of cancer detected in the long term follow up support the premalignant significance of non-invasive neoplasia while the 11 cases detected within one year from the original endoscopy fully demonstrated that non-invasive neoplasia frequently coexists with advanced cancer. Both of these observations could represent valid foundations in drawing a surveillance programme aimed at secondary gastric cancer prevention.
Table 1 .
Invasive cancer detected during follow up of non-invasive gastric neoplasia
| Gastric cancer detected after follow up longer than 12 months |
Gastric cancer detected within 12 months from initial diagnosis |
|||||||
|---|---|---|---|---|---|---|---|---|
| Histology at enrollment | Follow up (months)* | EGC | AGC | GC-nos | Follow up (months)* |
EGC | AGC | GC-nos |
| Low grade non-invasive neoplasia (99 cases) | 48 (38–80) | 5 | 1 | 2 | 1.5 (1–2) | 1 | 1 | 0 |
| High grade non-invasive neoplasia (25 cases) | 30 (13–72) | 7 | 1 | 3 | 2 (1–4) | 6 | 3 | 0 |
| Total | 35 (13–80) | 19 | 1.7 (1–4) | 11 | ||||
EGC, early gastric cancer (that is, UICC pathological stage I); AGC, advanced gastric cancer (that is, UICC pathological stages II-II-III); GC-nos, gastric cancer of unknown pathological stage.
*Mean (range).
Acknowledgments
The prospective study on gastric non-invasive neoplasia has been supported by the Veneto Region (project number 909/06-99) and granted by the Italian Office for Instruction and University Research (MTUR: Chiron project-July 2000).
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