Determinants of Long-term Survival Decades After Esophagectomy for Esophageal Cancer.

BACKGROUND: Long-term survival in esophagectomy patients with esophageal cancer is low due to tumor-related characteristics, with few reports of modifiable variables influencing outcome. We identified determinants of overall survival, time to recurrence, and disease-free survival in this patient cohort. METHODS: Adult patients who underwent esophagectomy for primary esophageal cancer from January 5, 2000, through December 30, 2010, at our institution were identified. Univariate Cox models and multivariable logistic regression analyses were used to identify associations between modifiable and unmodifiable patient and clinical variables and outcome of survival for the total cohort and a subgroup with locally advanced disease. RESULTS: We identified 870 patients with esophageal cancer who underwent esophagectomy. The median follow-up time was 15 years, and the 15-year overall survival rate was 25.2%, survival free of recurrence was 57.96%, and disease-free survival was 24.21%. Decreased overall survival was associated with the following unmodifiable variables: older age, male sex, active smoking status, history of coronary artery disease, advanced clinical stage, and tumor location. Decreased overall survival was associated with the following modifiable variables: use of neoadjuvant therapy, advanced pathologic stage, resection margin positivity, surgical reintervention, and blood transfusion requirement. The overall survival probability 6 years after esophagectomy was 0.920 (95% CI, 0.895-0.947), and time-to-recurrence probability was 0.988 (95% CI, 0.976-1.000), with a total of 17 recurrences and 201 deaths. CONCLUSIONS: Once patients survive 5 years, recurrence is rare. Long-term survival can be achieved in high-volume centers adhering to National Comprehensive Cancer Network guidelines using multidisciplinary care teams that is double what has been previously reported in the literature from national databases.

Genipin Crosslinks the Extracellular Matrix to Rescue Developmental and Degenerative Defects, and Accelerates Regeneration of Peripheral Neurons.

The peripheral nervous system (PNS) is essential for proper body function. A high percentage of the population suffer nerve degeneration or peripheral damage. For example, over 40% of patients with diabetes or undergoing chemotherapy develop peripheral neuropathies. Despite this, there are major gaps in the knowledge of human PNS development and therefore, there are no available treatments. Familial Dysautonomia (FD) is a devastating disorder that specifically affects the PNS making it an ideal model to study PNS dysfunction. FD is caused by a homozygous point mutation in ELP1 leading to developmental and degenerative defects in the sensory and autonomic lineages. We previously employed human pluripotent stem cells (hPSCs) to show that peripheral sensory neurons (SNs) are not generated efficiently and degenerate over time in FD. Here, we conducted a chemical screen to identify compounds able to rescue this SN differentiation inefficiency. We identified that genipin, a compound prescribed in Traditional Chinese Medicine for neurodegenerative disorders, restores neural crest and SN development in FD, both in the hPSC model and in a FD mouse model. Additionally, genipin prevented FD neuronal degeneration, suggesting that it could be offered to patients suffering from PNS neurodegenerative disorders. We found that genipin crosslinks the extracellular matrix, increases the stiffness of the ECM, reorganizes the actin cytoskeleton, and promotes transcription of YAP-dependent genes. Finally, we show that genipin enhances axon regeneration in an in vitro axotomy model in healthy sensory and sympathetic neurons (part of the PNS) and in prefrontal cortical neurons (part of the central nervous system, CNS). Our results suggest genipin can be used as a promising drug candidate for treatment of neurodevelopmental and neurodegenerative diseases, and as a enhancer of neuronal regeneration.

Agreement Between Upper Digestive Disease App and Provider Evaluation of Esophagectomy Symptoms in a Mobile App Tool.

BACKGROUND: The objective of this study was to assess the criterion validity of score thresholds for the Upper Digestive Disease (UDD) App. METHODS: From December 15, 2017, to December 15, 2020, patients presenting after esophagectomy were offered the UDD App concurrent with a provider visit. This tool consists of 67 questions including 5 novel domains. Score thresholds were used to assign patients to a good, moderate, or poor category on the basis of domain scores. Providers were given performance descriptions for each domain and asked to assign patients to a category on the basis of their clinical evaluation. The weighted κ statistic was used to determine the magnitude of agreement between classifications based on the patients' UDD App scores and the providers' clinical evaluation. RESULTS: Fifty-nine patients in the study (76% male; median age, 63 years [interquartile range, 57-72 years]) reported outcomes using the UDD App. Providers reviewed between 1 and 10 patients at a median time of 296.5 days (interquartile range, 50-975 days) after esophagectomy. The magnitude of agreement between patients and providers was moderate for dysphagia (κ = 0.52; P < .001) and reflux (κ = 0.42; P < .001). Dumping-related hypoglycemia (κ = 0.03; P = .148), gastrointestinal complaints (κ = 0.02; P = .256), and pain (κ = 0.05; P < .184) showed minimal agreement, with providers underestimating the symptoms and problems reported by patients in these domains. CONCLUSIONS: Although there was agreement between UDD App assessment and provider evaluation of dysphagia and reflux after esophagectomy, there was discordance of scoring for dumping-related symptoms and pain. Future research is needed to determine whether thresholds for pain and dumping domains need to be revised or whether additional provider education on performance descriptions is needed.

Upper Digestive Disease App for Electronic Patient-Reported Outcomes: A Mixed Methods Pilot Study.

BACKGROUND: Patient-reported outcomes (PROs) can enable communication of symptoms, function, and quality of life. Mobile devices capture PROs electronically (ePRO). The purpose of this study was to determine the feasibility and acceptability of collecting ePROs in esophagectomy patients using the upper digestive disease application (UDD App). METHODS: A single-group, mixed methods design was used to address the study purposes. A convenience sample of esophagectomy patients was recruited after resumption of an oral diet from January 2020 to December 2020. Demographic characteristics (age, sex) and clinical data (surgical procedure) were obtained after informed consent. Participants used the UDD App for 1 year, followed by scripted telephone interviews. Descriptive statistics and thematic analyses of the interviews were the primary data analyses. RESULTS: Sixty-four patients were enrolled (80% male; 62.9 ± 12 years old). Of these, 50 patients initiated 108 evaluations through the UDD app, with 98% completing the questionnaire on the first attempt, indicating feasibility. A subset of 32 patients participated in the scripted telephone interview. Participants (74%) reported high computer literacy; all reported that using the UDD App was easier than or equivalent to a paper form. Interview themes revealed value of the app for identifying problems and enhanced communication with providers and caregivers, with an overall appreciation for the convenience of remote monitoring but concerns about data privacy. CONCLUSIONS: The UDD App is feasible and acceptable for collecting ePROs in esophagectomy patients. Future work will determine whether the UDD App improves symptoms, function, and quality of life.