Overweight and obesity are important lifestyle-related public health problems in the world[17], and the number of overweight or obese people has already surpassed the number of underweight people for the first time according to recent studies[18]. In the literature, overweight and obesity is usually determined using the easily calculated BMI. BMI is classified as normal (BMI < 25 kg/m2 ), overweight (BMI 25–30 kg/m2 ), and obese (BMI ≥ 30 kg/m2) according to the WHO standard[19]. In this study, the Chinese standard[20, 21] was used and BMI was classified as low (BMI < 18.5 kg/m2), normal (BMI 18.5–24 kg/m2), high (BMI ≥ 24 kg/m2), as all the patients enrolled were Chinese.
Recently, increasing attention has been paid to VFA and BMI as obesity indexes. Previous studies found VFA to be superior to BMI in accurately and effectively predicting the effect of obesity on adverse postoperative outcomes[22–24] after radical colectomy as well as radical gastrectomy. However, all the studies focused on the comparison of two indications and whether VFA is a better parameter than BMI remains controversial. Similarly, our previous study also only demonstrated that VFA was superior to BMI in predicting PM based on the direct comparison of two variables, thus, we designed this prospective cohort study with the aim of investigating the role of VFA for PM after eliminating BMI differences. To the best of our knowledge, this is the first prospective cohort study focusing on this contentious question.
Despite the controversy of which is better, both VFA and BMI are obesity parameters. There was a positive correlation between BMI and VFA in general in the study although patients with a high BMI may not have a high VFA. Considering that patients were subdivided according to the BMI, the cutoff value for VFA in the previous study was inappropriate for the overall patients. We thus performed ROC curve analysis in all the three BMI groups and cutoff values of 67.28 cm2, 88.03 cm2 and 175.32 cm2, respectively, were defined for high VFA, which was quite different from our previous work[16]. However, there is still a lack of consensus on the VFA cutoff for Chinese and VFA cutoff varies from study to study[25, 26]. Using these cutoffs, 15.52%, 40.15%, 31.28% of patients in our cohort met this definition of high VFA, and these high VFA patients were more likely to develop PM than low VFA patients.
We further confirmed that high VFA was an independent risk factor for PM in the normal BMI group. This may be partly because of the state of low grade chronic inflammation of adipose tissue in obesity. By generating reactive oxygen species (ROS), which have mitogenic properties at low concentrations, tumor further progressed[27,28]. On the other hand, insulin resistance in obese patients may promotes secretion of IGF-1 and thus promote mitogenic and proangiogenic pathways and inhibit apoptosis, consequently cause a majority of the proliferative effects and promote tumor development and metastasis[29]. However, no such results were found in the low and high BMI groups. For patients with low BMI, only 15.52% of the patients were determined as high VFA. Combined with the low incidence of PM (6.02%, 7 in 116) in this group, even no factor was found to be independently associated with PM in the multivariate analysis, which may be attributed to statistical bias to some extent. For high VFA patients, the incidence of the PM in the study was the highest (31.28%, 61 in 195), which was also apparently higher than that reported in other studies[30, 31]. However, the prediction of VFA for PM may be severely weakened by the high BMI of the population.
Many studies have focused on evaluating the PM status in gastric cancers[31–33]. Despite the poor overall sensitivity[34], CT is still the most common tool for detecting PM before operation. Although a previous study[16] already demonstrated the relationship between VFA and PM, this study also found VFA was relevant only in normal BMI patients. As an abdominal CT scan is routinely performed as a common test for preoperative evaluation, the development of software technology also makes VFA measurements easier. Thus, more attentions should be paid to high VFA patients, especially for high VFA and normal BMI patients.
This study has some limitations. First, our study sample size was small, 87 patients were diagnosed with PM and only 7 PM patients were found in the low BMI group, which may seriously affect the accuracy of the analysis. Second, this was a single-center study, and most of the patients came from Southeast China, thus, the findings may not be generalizable to other settings. As body shape is inherently different between locations and races, our results need to be validated by further studies from other medical centers. Third, although ROC curves are appropriate for establishing VFA cutoff values in each group, a standardized cutoff value is urgently needed. Finally, a randomized clinical trial was urgently need to verify the results of this study that reduce VFA may decrease the risk of peritoneal metastasis in GC patients with normal BMI.
In conclusion, our previous study demonstrated VFA is a better obesity index than BMI in predicting abdominal metastasis. This study further determined the relationship between VFA and PM of GC across patients with different BMI. We found that GC patients with high VFA in and normal BMI were at higher risk of PM compared to those with low or high BMI. Thus, more attention should also be paid to GC patients with high VFA and normal BMI. Additionally, for GC patients with normal BMI, intervention measures should be taken to reduce visceral fat area, so as to reduce the risk of peritoneal metastasis.