4. Discussion
dysphagia, neurologic disorders, Weight loss, ALS, dementia, oncologic disease, decline in nutritional status, swallowing difficulties, constipation, dysbiosis, long-term dysphagia, increases infectious, malnutrition, refeeding syndrome, gastrointestinal dysfunction, intestinal dysfunction, trauma
ESOPHAGEAL CANCER, CEREBROVASCULAR DISORDERS, DYSPHAGIA, DETACHMENT, SWALLOWING DIFFICULTIES, NEUROLOGIC DISORDERS, NEURODEGENERATIVE DISEASE, AMYOTROPHIC LATERAL SCLEROSIS, MINOR, DISEASE, DISORDERS, DYSFUNCTION, ATROPHY, PERIOPERATIVE COMPLICATION, REFEEDING SYNDROME, MALNUTRITION, GASTROINTESTINAL DYSFUNCTION
Protein–energy malnutrition is a highly prevalent condition in gastroenterology clinical practice, especially when food intake is severely reduced for long periods. It is associated with poor outcomes in ambulatory and hospitalized patients, causes prolonged hospital stays, increases infectious and perioperative complications, leads to higher healthcare costs, and increases morbidity and mortality [Enteral nutrition through PEG is an effective approach to manage malnutrition when oral feeding is compromised. Several clinical conditions have become common indications for PEG feeding, mostly in cases of long-term dysphagia due to oncologic disease (mainly head and neck or esophageal cancer) and neurologic disorders like amyotrophic lateral sclerosis (ALS), cerebrovascular disorders, dementia, central nervous system trauma, and congenital or neonatal abnormalities [In the current study, the authors analyzed 30 patients referred for PEG with significantly low caloric intake and absence of previous nutritional support via tube feeding, looking for histologic and ultrastructural changes in the intestinal mucosa. A large number of patients were diagnosed with ALS, as a significant reduction in oral ingestion is commonly observed from the early stages of this neurodegenerative disease and our team is a reference center for enteral feeding in ALS patients. During the course of ALS, a decline in nutritional status is common and malnutrition is an independent, negative, prognostic indicator for survival. Weight loss may be explained by several factors, including reduced food intake associated with decreased strength for food manipulation and chewing, impaired salivary secretion, swallowing difficulties, constipation, and fear of pulmonary aspiration. ALS patients have also been associated with significant gastrointestinal dysfunction that contributes to malnutrition as the enteric nervous system may become affected, motor neuron disorders develop, and dysbiosis may occur [The histopathologic evaluation of duodenal biopsies showed a low prevalence of mucosal atrophy (10%) according to the standard analysis described by the Marsh–Oberhuber classification. However, the hypothesis of impaired gut function with the loss of absorption induced by prolonged fasting may manifest in more subtle changes like reduced enterocyte mass, intestinal inflammation, and increased bacterial translocation, not commonly easily assessed in clinical practice [The ultrastructural analysis of the duodenal mucosa also revealed changes at the cellular level. After a significant period of reduced energy intake, enterocytes displayed changes in the striated plate with disarrangement of microvilli. In these cells, increased autophagy was evident, demonstrated by the presence of cytoplasmic vacuoles. Dense bodies and vesiculation of the endoplasmic reticulum were also present. Beyond the evidence of enterocyte dysfunction, an increased length of intercellular spaces and the cell detachment of basal membranes may also contribute to compromised absorption. All of these changes were not observed in the controls and seemed to revert after 3 to 6 months of enteral nutrition with adequate intake. These findings are innovative and reflect metabolic derangement and impaired enterocyte absorptive capacity. As no previous study has evaluated the impact of prolonged fasting in intestinal mucosa using villi length measurement or electron microscopy, these findings represent a major advance in the comprehension of fasting-induced intestinal dysfunction.The present study also displays some minor limitations. First, 30 patients were initially included and assessed at baseline; however, only 14 completed the follow-up, and the duodenal biopsies could be reanalyzed after refeeding—this occurred mostly because one-third died before endoscopic control due to disease evolution, one patient recovered from dysphagia, and six were lost to follow-up. Second, the histologic and ultrastructural analysis was performed in patients in two different periods, and the findings were compared to healthy controls; however, this evaluation was not blinded. Nevertheless, the biopsies were analyzed by at least two operators using the same standardized protocols to avoid inter-observer variability. Finally, the association of the structural anomalies found in the duodenal mucosa and a potential decrease in enterocyte absorptive capacity is indirect as no “functional” analysis was performed to assess it. In fact, there is no gold standard method to study absorption in this clinical setting and functional tests are not widely available in our country. An immunohistochemistry-based analysis of the intestinal mucosa to study the expression of digestive hormones is also planned by our group to overcome this bias and reinforce the obtained results. Metabolomics may also help to assess the impact of fasting and subsequent refeeding in absorptive mechanisms. Further studies with a similar patient population are planned, aiming to define possible serum biomarkers involved in refeeding syndrome and its impact on nutritional and clinical prognosis.