Our prospective cohort study of ED therapy in patients with unresectable PC suggested that the administration of an ED during systemic chemotherapy might improve the nutritional status in comparison to a historical cohort that did not receive an ED. The impact of the ED on the prognosis was unclear. Although cancer progression and the serum CA19-9 level in the ED group were worse in comparison to the historical cohort, the median survival time did not differ between the two groups. We believe that the role of ED in OS should be further investigated.
Patients with PC are known to be prone to EPI especially when the pancreatic duct is obstructed by the tumor [4]. Saito et al. showed that among patients with PC who underwent an NBT-PABA test, the results were lower than the normal threshold in 90% of the patients [8, 9]. The admission that the NBT-PABA test is not an accurate test of the pancreatic exocrine function, the results, and tendency for patients with low NBT-PABA results to show low albumin and prealbumin levels, suggested that EPI is quite prevalent in patients with PC, even in patients with PC located in the body or tail of the pancreas. The ED used in the present study (Elental®) is low in fat, is a good source of nitrogen and amino acids, and rarely requires a fully functional digestive system. Thus, we used this ED for patients with PC, without considering the cancer location. However, adherence to the ED was often low due to the odor and taste. In our study, pharmacists explained the efficacy of the ED and advised the patients how to take it individually using a leaflet. However, only thirty patients (60%) could take Elental® over 300 kcal/day. The present study was not sufficient to evaluate the effectiveness of the ED. It is essential to improve the flavor or the approach to counselling.
It has also been reported that Elental® does not seriously affect blood sugar control in diabetes patients, suggesting that its interference in perioperative blood sugar control is of minimal concern [10]. However, our study revealed that serum HbA1c levels were increased in the ED group. We hypothesize that the insulin levels of patients with PC decrease in comparison to patients with other cancers because the endocrine pancreas cells decline due to obstructive chronic pancreatitis. Moreover, 80% of Elental® consists of carbohydrate. Thus, blood sugar is a concern, and self-injected insulin must be introduced immediately for PC patients who receive ED therapy.
The nutritional status can potentially influence the clinical outcomes of chemotherapy for PC because serum albumin is a known prognostic factor for advanced PC [11]. Thus, we decided to use the serum albumin level as the primary endpoint. According to our analysis, the serum albumin levels of patients in the ED group were slightly decreased at 3 months, whereas in the historical cohort, the serum albumin levels showed a much greater decrease. While there were no significant differences, these results suggested that an ED may maintain the nutritional status during chemotherapy for PC. In addition, the analysis of the serial changes in the serum total protein level and PNI revealed a significant decrease in the historical cohort. Many studies found that the PNI is an independent prognostic indicator for various malignant tumors, including PC [12–14]. The preservation of the PNI may reflect that the ED maintained the nutritional status.
The present study was associated with some limitations. First, there was a selection bias in our study. To evaluate the impact of ED at 3 months after the introduction of chemotherapy, we excluded patients who developed early disease progression. Second, there were differences in the background characteristics. Cancer progression and the serum CA19-9 level in the ED group were substantially worse in comparison to the historical cohort. We consider that this occurred incidentally and because this was not a randomized controlled study.
Additionally, we evaluated BMI as one of the parameters of the nutritional status; however, the precise body composition was not evaluated in this study. It is possible that body weight might include the weight of ascites or edema; however, few patients in our study population had massive ascites (4 in the ED group and 1 in the historical cohort), and would have had little effect on our results.
In conclusion, this prospective study demonstrated that ED tended to improve the nutritional status during chemotherapy for unresectable PC. A prospective randomized study should be performed to evaluate the efficacy of ED therapy in patients with unresectable PC who receive systemic chemotherapy.