Nutritional problems are among the most important problems post curative gastrectomy. This study found that preoperative ferritin level, premenopausal women and duodenal bypassing reconstruction were independent risk factors for FD among the patients with normal baseline ferritin levels.
Iron is closely related to the hematopoietic process, and iron deficiency is a major cause of anemia after gastrectomy . However, iron status after gastrectomy varies widely among patients. To evaluate iron supplementation after gastrectomy, we focused on ferritin levels. Ferritin is a blood protein that stores and releases iron; thus, it reflects the amount of iron stored . Dietary iron is absorbed through the polarized intestinal epithelial cells of the duodenum and proximal jejunum. Iron exists in an oxidized form, which has low water solubility and is not available in vivo; thus, it should be stored in a ferritin-bound form. Ferritin levels positively correlate with total body iron stores under steady-state conditions, and can be used as the most convenient laboratory test to estimate iron stores .
A ferritin level lower than the normal level indicates an iron deficiency. Bleeding, such as menstruation, may also result in lower ferritin levels . High ferritin levels could indicate high iron storage. However, inflammatory conditions, infection, postoperative state, liver disease, rheumatoid arthritis, some types of cancer, and hyperthyroidism may also elevate ferritin levels . In this study, we focused on changes in the ferritin level in association not only with gastrectomy type or reconstruction method, but also with the patients’ characteristics (e.g., PMP status, smoking history, and baseline ferritin level). PMP patients are at higher risk of iron deficiency than men and menopausal women. Smoking is also known to increase ferritin levels . We also found that the baseline ferritin level was an influencing factor of postoperative FD. Specifically, a baseline ferritin level < 55.7 µg/L was a significant risk factor for FD. Multivariate analysis also showed that PMP, food bypass through the duodenum, and low baseline ferritin levels increased the risk of FD in both the high-risk and low-risk groups.
There have been several studies on the incidence of iron deficiency after gastrectomy, but none on the risk factors for FD, which was the focus of this study. Iron depletion after gastrectomy is a long-standing subject of interest regarding the nutritional aspect after gastrectomy. Kim et al. reviewed the medical records of 558 patients who underwent curative gastrectomy . They found that the cumulative incidence of iron deficiency gradually increased with time, postoperatively. Furthermore, Billroth-I anastomosis was the best reconstruction strategy for preventing iron deficiency. Lee et al. found that Billroth-II anastomosis and female sex were associated with a higher prevalence of iron deficiency among 381 patients . The authors defined iron deficiency as a ferritin level < 30 µg/L. In contrast, we defined FD as a ferritin level < 15 µg/L, which may have attributed to a lower incidence of iron depletion. We followed the World Health Organization Guideline regarding the use of ferritin concentrations to assess iron status in individuals and populations, which may be useful for determining whether patients are critically ill.
With respect to the influence of sex on ferritin levels, some studies divided patients into male and female groups. However, in the real world, the risk of iron depletion is similar between postmenopausal female and male patients. Thus, we only included patients with ferritin levels > 15 µg/L, regardless of sex. Furthermore, possible menstruation status was included in the categorization, thereby increasing statistical power. Gastrectomy reconstruction method has been a highly researched topic in the field of gastric cancer, especially distal or proximal gastrectomy. Korean guidelines for gastric cancer treatment show that there is no significant difference in the survival or quality of life benefit, except for bile reflux, in Billroth-I, Billroth-II, and Roux-en-Y anastomosis for distal gastrectomy.
Studies on iron depletion anemia have suggested that duodenal bypassing anastomosis is inferior to duodenum passing anastomosis . This study shows that any type of duodenal food passage can prevent iron depletion. Additionally, we found that the low-risk group is a candidate for duodenal bypass anastomosis. Therefore, our risk stratification method can be used to determine the appropriate type of anastomosis needed. Among patients in which proximal gastrectomy is indicated; most have early gastric cancer in the proximal portion of the stomach. In such patients, the decision for the type of surgical procedure depends on the extent of resection needed. Total gastrectomy usually only has one anastomosis choice, duodenal bypassing. Meanwhile, other surgical options such as esophagogastrostomy, lower esophageal sphincter-preserving proximal gastrectomy, and double tract anastomosis allow food to pass through the duodenum . Proximal gastrectomy is strongly recommended for patients at risk of iron depletion.
The clinical implications of FD need to be considered. With respect to long-term nutritional factors, there was no significant difference in postoperative body weight between the FD and FnD groups, whereas postoperative hemoglobin level was significantly lower in the FD group from the postoperative 1 year period. We need to further evaluate the implications of risk factors in iron supplement strategies. Iron deficiency is one of the most important nutritional problems in post-gastrectomy patients. Although many studies have investigated iron depletion in gastrectomy patients, our study shows the natural response or change in iron depletion among long-term survivors of gastric cancer after gastrectomy. We only included patients with normal baseline ferritin levels who were followed up for 3 years, without gastric cancer recurrence.
This study had limitations. First, this was a retrospective study, and PMP was arbitrarily defined as females < 55 years. There could have been patients < 55 years who underwent hysterectomy or were post-menopausal. Prospective studies on the menopausal status of PMP patients are needed to investigate its impact on ferritin levels. However, PMP was found to be an independent risk factor for FD. Second, ferritin might be influenced by inflammatory conditions such as sepsis or postoperative complications, and these conditions were not considered in this study. Although we evaluated the incidence of FD, we did not compare the mean with the standard deviation. As a result, the data on the impact of other inflammatory conditions on FD may be limited. Third, we did not consider other iron-related parameters, such as transferrin and iron-binding capacity, serum iron, and total iron, which also give an indication of iron status or iron activation ability. Further studies using other relevant parameters are required in the future.
In conclusion, postoperative FD is highly common after gastrectomy for gastric cancer. The patient’s risk factors (e.g., PMP, food passage through the duodenum, and baseline ferritin level) can be used to predict postoperative FD, thereby allowing physicians to determine the need for iron supplementation.