Delayed Gastric Emptying Post-Esophagectomy: A Single-Institution Experience.

OBJECTIVE: Delayed gastric emptying (DGE) is a common functional disorder after esophagectomy in patients with esophageal carcinoma. Management of DGE varies widely and it is unclear how comorbidities influence the postoperative course. This study sought to determine factors that influence postoperative DGE. METHODS: This retrospective study evaluates patients who underwent esophagectomy with gastric pull-up between 2007 and 2019. The cohort was stratified in various ways to determine if postoperative care and outcomes differed, including patient demographics, comorbidities, intraoperative and postoperative procedures. RESULTS: During the study period, 149 patients underwent esophagectomy and 37 had diabetes. Overall incidence of DGE, as defined in this study, was 76.5%. Surgery type was significantly different between DGE and normal emptying cohorts (P = 0.005). Comparing diabetic and nondiabetic patients, there was no significant difference noted in DGE (P = 0.25). Additionally, there was no difference in presence of DGE for patients who underwent any intraoperative pyloric procedure compared to those who did not (P = 0.36). Of significance, all 16 patients with chronic obstructive pulmonary disease had a delay in gastric emptying (P = 0.01). CONCLUSIONS: A higher proportion of patients with DGE post-esophagectomy were identified compared to the literature. There is little consensus on a true definition of DGE, but we believe this definition identifies patients suffering in the immediate postoperative period and in follow-up. There is no evidence to support a different postoperative course for patients with diabetes, but the link between chronic obstructive pulmonary disease and DGE warrants further investigation.

Metabolic perturbations in classic galactosemia beyond the Leloir pathway: Insights from an untargeted metabolomic study.

Classic galactosemia (CG) is an autosomal recessive disorder that impacts close to 1/50000 live births in the United States, with varying prevalence in other countries. Following exposure to milk, which contains high levels of galactose, affected infants may experience rapid onset and progression of potentially lethal symptoms. With the benefit of early diagnosis, generally by newborn screening, and immediate and lifelong dietary restriction of galactose, the acute sequelae of disease can be prevented or resolved. However, long-term complications are common, and despite many decades of research, the bases of these complications remain unexplained. As a step toward defining the underlying pathophysiology of long-term outcomes in CG, we applied an untargeted metabolomic approach with mass spectrometry and dual liquid chromatography, comparing thousands of small molecules in plasma samples from 183 patients and 31 controls. All patients were on galactose-restricted diets. Using both univariate and multivariate statistical methods, we identified 252 differentially abundant features from anion exchange chromatography and 167 differentially abundant features from C18 chromatography. Mapping these discriminatory features to putative metabolites and biochemical pathways revealed 14 significantly perturbed pathways; these included multiple redox, amino acid, and mitochondrial pathways, among others. Finally, we tested whether any discriminatory features also distinguished cases with mild vs more severe long-term outcomes and found multiple candidates, of which one achieved false discovery rate-adjusted q < 0.1. These results extend substantially from prior targeted studies of metabolic perturbation in CG and offer a new approach to identifying candidate modifiers and targets for intervention.

Presentation, progression, and predictors of ovarian insufficiency in classic galactosemia.

Classic galactosemia (CG) is an inherited metabolic disorder that affects about 1 in 50,000 live births in the United States and many other countries. With the benefit of early detection by newborn screening and rapid dietary restriction of galactose, generally achieved by removing dairy from the diet, most affected infants are spared the acute and potentially lethal symptoms of disease. Despite early detection and life-long dietary intervention, however, most patients grow to experience a constellation of long-term complications that include premature ovarian insufficiency in the vast majority of girls and young women. Our goal in the study reported here was to define the presentation, progression, and predictors of ovarian insufficiency in a cohort of 102 post-pubertal girls and women with CG. To our knowledge, this is the largest cohort studied to date. We found that 68% of the girls and women in our study achieved spontaneous menarche, while 32% achieved menarche only after starting hormone replacement therapy (HRT). Of those who achieved spontaneous menarche, fewer than 50% were still cycling regularly after 3 years, and fewer than 15% were still cycling regularly after 10 years. Of factors tested for possible association with spontaneous menarche, only detectable (≥ 0.04 ng/mL) plasma anti-Müllerian hormone (AMH) level was significant. These results extend substantially from prior studies and confirm that detectable plasma AMH is a useful predictor of ovarian function in girls and women with CG.

Rigor of non-dairy galactose restriction in early childhood, measured by retrospective survey, does not associate with severity of five long-term outcomes quantified in 231 children and adults with classic galactosemia.

One of many vexing decisions faced by parents of an infant with classic galactosemia (CG) is how carefully to restrict non-dairy galactose from their growing child's diet. Until recently, many experts recommended vigorous lifelong dietary restriction of milk and all high-galactose dairy products as well as some non-dairy sources of galactose such as legumes and specific fruits and vegetables. Recently, experts have begun to relax their recommendations. The new recommendations, that restrict only high galactose dairy products, were made in the face of uncertainty, however, because no sufficiently powered study had been reported testing for possible association between rigor of non-dairy galactose restriction and severity of long-term outcomes in CG. Here we describe the largest study of diet and outcomes in CG reported to date, conducted using information gathered from 231 patients with CG and 71 unaffected sibling controls. We compared rigor of dietary galactose restriction, measured using a 4-point scale by a retrospective parent-response survey, with outcomes including growth, adaptive behaviors, receipt of speech therapy, receipt of special educational services, and for girls and women, a plasma marker of ovarian function (AMH). Our results confirmed the expected differences between patients and controls, but among patients showed no significant association between rigor of non-dairy galactose restriction in early childhood and any of the outcomes quantified. Indeed, some weak associations were seen suggesting that rigorous restriction of non-dairy galactose may be deleterious rather than beneficial. Despite limitations, these findings support the ongoing trend toward diet liberalization with regard to non-dairy sources of galactose for children and adults with classic galactosemia.