Clinical epidemiology and outcomes of patients with gastric intestinal metaplasia in the Los Angeles County System

Gastric cancer is the fifth most common cancer and the third leadingcause of cancer-related deaths worldwide [1]. It occurs more frequently in men and people of African-American, Hispanic, and Asian backgrounds [2]. In the United States (US), the incidence of gastric cancer is approximately 26,000 cases per year, representing the 15th most common cancer type [1]. Gastric intestinal metaplasia (GIM) is a known precursor lesion to gastric adenocarcinoma (GAC). Esophagoduodenoscopy (EGD) provides the ability to detect this precursor lesion and obtain targeted biopsies. However, given the dearth of epidemiological and other clinical data, there is no consensus on neither the utility of GAC screening nor optimal surveillance intervals in the US for patients with biopsy-proven GIM [3, 4].

The American Society for Gastrointestinal Endoscopy (ASGE) has recommended surveillance EGD in patients with biopsy-proven GIM who have increased risk for GAC due to ethnic background or family history but does not specify optimal surveillance intervals [3]. Other international societies have recommended individualized screening and surveillance strategies for people with extensive GIM, incomplete GIM subtype, family history of GAC, or persistent Helicobacter pylori (H. pylori)gastritis, in addition to ethnic minorities and first-generation immigrants from countries with a high incidence of GAC [5, 6]. In light of the limited available data, the American Gastroenterological Association published guidelines recommending the eradication of H. pyloriin patients with GIM but no definitive recommendations for endoscopic surveillance [4]. Though GAC is overall rare in the US compared to other cancers, minority populations which are most affected by it are relatively understudied [7‐9]. Considering modern endoscopic capabilities, the presence of a sizeable minority population receiving healthcare in the US, and the high mortality rates associated with GAC, it is important to gain a better understanding of the clinical features and outcomes of GIM in order to inform optimal endoscopic surveillance strategies. This is particularly important in populations at increased risk for GIM and/or GAC, such as the Hispanic-predominant Los Angeles Department of Health Services (LADHS) patient population [10].

We performed a multicenter, retrospective cohort study of patients seen at the three medical centers comprising the LADHS system with biopsy-proven GIM. Our aim was to examine the demographics, clinical features, and outcomes of these patients, as this may ultimately inform the utility of endoscopic surveillance practices in minority ethnic populations.

In this multicenter retrospective cohort study of patients with biopsy-proven GIM, the majority of our cohort was comprised of Hispanic and Asian patients, two ethnic minorities known to have an increased risk of GAC [2]. In addition, a greater than average incidence of prior H. pyloriinfection was seen in our cohort, which is known to occur more frequently in ethnic minorities and is a recognized driver of GIM [11]. Our cohort also had a high incidence (5%) of GAC at the time of index EGD with biopsy-proven GIM, which corroborates the need to explore the utility of GIM surveillance particularly in ethnic minorities [12]. The recommended interval for repeat EGD for GIM surveillance varied greatly in our study population, with no recommendation for further GIM surveillance in a majority of patients, followed by 2–3 years as the most common time interval if surveillance was recommended. This variability in surveillance recommendations is likely driven by the lack of consensus in the US on the need for GIM surveillance and the optimal time intervals for surveillance when pursued.

Of the patients who underwent a repeat EGD with biopsy during the study period, none developed low- or high-grade dysplasia nor GAC. A small proportion (14%) had multifocal GIM detected at repeat EGD, though it is possible a portion of these patients already had multifocal GIM at index EGD that was not appreciated (e.g. due to limited biopsies). Our data suggest that the progression of GIM to low- or high-grade dysplasia and GAC may not occur within a 1–2 year period, and the same likely applies to progression to multifocal GIM. However, we are limited in our ability to propose an optimal surveillance interval for GIM given that only a minority of patients diagnosed with GIM underwent surveillance EGD as well as the relatively limited median follow-up time of patients in our study.

In our subgroup analysis of patients with multifocal GIM found at repeat EGD, in comparison to patients without multifocal GIM at repeat EGD, there was a greater percentage of females with multifocal GIM, which is not an established risk factor for GIM or GAC. Similar to prior literature, there was a greater percentage of patients with a history of H. pyloriamongst those who were diagnosed with multifocal GIM at repeat EGD [1, 3]. Smoking history and a family history of GAC, identified as risk factors for GAC and GIM progression in prior studies, were not reproduced as significantly more prevalent in patients with multifocal GIM at repeat EGD [13, 14].

It should be emphasized that most patients in our study had gastric biopsies taken in one location at index EGD. Of the patients who didhave multifocal GIM at repeat EGD, the majority did not have biopsies taken in more than one location at index EGD. Moreover, there were patients without visualized abnormalities endoscopically who had multifocal GIM diagnosed on biopsy. This highlights the variability in the number of biopsies routinely obtained during diagnostic EGD when a diagnosis of GIM is not known [15, 16]. It also suggests that the true incidence of multifocal GIM may be higher than what is diagnosed based on current biopsy practices.

Our study had several limitations. Although we abstracted data from a five-year time period and achieved a cumulative follow-up of 119 patient-years, the median duration of follow-up from the time of index EGD to repeat EGD and last clinic encounter was less than two years. Additionally, the limited number of follow-up EGDs and few patients with documented progression to multifocal GIM precluded the use of multiple logistic regression to model risk factors for progression and time to progression of GIM that could better inform surveillance intervals in our population of interest. Furthermore, univariate analyses to compare characteristics between progressors and non-progressors were not meaningful given that the repeated use of hypothesis testing increases the chance of a Type I error and is not a suitable alternative when the number of outcomes is insufficient for multivariate analysis (Supplementary Table 1). These limitations highlight the challenges in abstracting robust data in safety-net settings where low follow-up rates are common and the importance of developing strategies to mitigate this [17]. Furthermore, cost was not measured or modeled in our study; however, we believe that appropriately spacing out surveillance EGDs based on the natural history of GIM would not only provide healthcare cost benefits, but also decrease burden on patients.

In summary, we describe a multicenter, retrospective study of patients with biopsy-proven GIM in a large, underserved county health system with predominantly minority patients, with a historically higher incidence of GAC. Our cohort demonstrated a 5% incidence of GAC at the time of index EGD with biopsy-proven GIM, emphasizing a need for more informed surveillance guidelines applicable to this patient population. During our study period and a cumulative follow-up of 119 patient-years, there was no apparent progression to low or high-grade dysplasia nor GAC and low incidence of multifocal GIM. Our data suggest that progression to dysplasia or GAC is unlikely to occur within a 1–2 year period. However, limitations in our dataset preclude identification of optimal surveillance intervals. Our study highlights variability in surveillance recommendations and biopsy sampling at index EGD. The limited median follow-up periods in our study also emphasizes the challenges in collecting longitudinal data in safety-net settings that has likely contributed to the paucity of data in ethno-racial and other minority populations that could otherwise inform evidence-based surveillance practices. Randomized controlled trials incorporating a diverse patient population may be needed in order to better elucidate the need for, approach to, and frequency of surveillance endoscopy for biopsy-proven GIM.