Preoperative risk factors for anastomotic leak after esophagectomy with gastric reconstruction: A 6-year national surgical quality improvement (NSQIP) database analysis.

BACKGROUND: Anastomotic leak is a serious complication after esophagectomy that has been associated with worse outcomes. However, identifying patients at increased risk for anastomotic leak remains challenging. METHODS: Patients were included from the 2016 to 2021 National Surgical Quality Improvement Project database who underwent elective esophagectomy with gastric reconstruction for cancer. A multivariable logistic regression model was used to identify risk factors associated with anastomotic leak. RESULTS: A total of 4,331 patients were included in the study, of whom 647 patients experienced anastomotic leak (14.9%). Multivariable logistic regression revealed higher odds of anastomotic leak with smoking (adjusted odds ratio 1.24, confidence interval 1.02-1.51, P = .031), modified frailty index-5 score of 1 (adjusted odds ratio 1.44, confidence interval 1.19-1.75, P = .002) or 2 (adjusted odds ratio 1.52, confidence interval 1.19-1.94, P = .000), and a McKeown esophagectomy (adjusted odds ratio 1.44, confidence interval 1.16-1.80, P = .001). Each 1,000/µL increase in white blood cell count was associated with a 7% increase in odds of anastomotic leak (adjusted odds ratio 1.07, confidence interval 1.03-1.10, P = .0005). Higher platelet counts were slightly protective, and each 10,000/ µL increase in platelet count was associated with 2% reduced odds of anastomotic leak (adjusted odds ratio 0.98, confidence interval 0.97-0.99, P = .001). CONCLUSION: In this study, smoking status, frailty index, white blood cell count, McKeown esophagectomy, and platelet counts were all associated with the occurrence of anastomotic leak. These results can help to inform surgeons and patients of the true risk of developing anastomotic leak and potentially improve outcomes by providing evidence to improve preoperative characteristics, such as frailty.

COVID-19-induced Esophageal Necrosis Requiring Emergent Total Esophagectomy in a Vaccinated Patient.

Acute esophageal necrosis may be a potential complication of Coronavirus Disease 2019 (COVID-19). COVID-19 has been associated with a variety of sequelae, including acute respiratory distress syndrome, myocarditis, and thromboembolic events. Here, we present a case of a 43-year-old male who was admitted for acute necrotizing pancreatitis and found to have COVID-19 pneumonia. He subsequently developed acute esophageal necrosis requiring a total esophagectomy. Currently, there are at least five other reported cases of esophageal necrosis with concomitant COVID-19 infection. This case is the first requiring esophagectomy. Future studies may establish esophageal necrosis as a known complication of COVID-19.

Implications of liver donor age on ischemia reperfusion injury and clinical outcomes.

The aging process causes detrimental changes in a variety of organ systems. These changes include: lesser ability to cope with stress, impaired repair mechanisms and decreased cellular functional reserve capacity. Not surprisingly, aging has been associated with increased susceptibility of donor heart and kidneys grafts to ischemia reperfusion injury (IRI). In the context of liver transplantation, however, the effect of donor age seems to be less influential in predisposing the graft to IRI. In fact, a widely comprehensive understanding of IRI in the aged liver has yet to be agreed upon in the literature. Nevertheless, there have been many reported implications of increased liver donor age with poor clinical outcomes besides IRI. These other poor outcomes include: earlier HCV recurrence, increased rates of acute rejection and greater resistance to tolerance induction. While these other correlations have been identified, it is important to re-emphasize the fact that a unified consensus in regard to liver donor age and IRI has not yet been reached among researchers in this field. Many researchers have even demonstrated that the extent of IRI in aged livers can be ameliorated by careful donor selection, strict allocation or novel therapeutic modalities to decrease IRI. Thus, the goals of this review paper are twofold: 1) To delineate and summarize the conflicting data in regard to liver donor age and IRI. 2) Suggest that careful donor selection, appropriate allocation and strategic effort to minimize IRI can reduce the frequency of a variety of poor outcomes with aged liver donations.

Epigenetic reprogramming of melanoma cells by vitamin C treatment.

BACKGROUND: The loss of 5-hydroxymethylcytosine (5hmC) has been identified as a novel epigenetic hallmark for melanoma. One of the known mechanisms underlying the loss of 5hmC is the decrease in expression of ten-eleven translocation family dioxygenase (TET) genes, which encode enzymes that catalyze the generation of 5hmC. Overexpressing TET2 was shown to partially reestablish a normal 5hmC profile in melanoma and decrease invasiveness in rodents. However, the feasibility to overexpress TETs in patients remains unclear. We and others have recently demonstrated that TETs require vitamin C as a cofactor to generate 5hmC. This finding prompted us to test whether vitamin C, as an alternative to overexpressing TETs, could rebuild 5hmC content in melanoma. RESULTS: Consistent with previous reports, we found that the expression of TETs was decreased in various melanoma cell lines. In contrast, the expressions of sodium-dependent vitamin C transporters (SVCTs) were down-regulated in cell lines derived from melanoma metastases. Treatment of vitamin C at the physiological level (0.1 mM) promoted the content of 5hmC in melanoma cell lines derived from different stages toward the level of healthy melanocytes, which was comparable to the effect of overexpressing TET2. Vitamin C treatment decreased the malignancy of metastatic A2058 cells by inhibiting migration and anchorage-independent growth, while not exerting any effect on the rate of proliferation. Further, vitamin C treatment caused alterations in genome-wide transcriptions shown by RNA-seq, predominantly in ArhGAP30 and genes involved in extracellular matrix remodeling, which could underlie the decreased malignant phenotypes. CONCLUSIONS: Our data support the idea that vitamin C treatment increases 5hmC content in melanoma cells, while causing a decrease in tumor-cell invasiveness and clonogenic growth in soft agar. Thus, vitamin C could be a potential epigenetic treatment for melanoma.

Ascorbate-induced generation of 5-hydroxymethylcytosine is unaffected by varying levels of iron and 2-oxoglutarate.

Tet (ten-eleven translocation) methylcytosine dioxygenases, which belong to the iron and 2-oxoglutarate (2OG)-dependent dioxygenase superfamily, convert 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) in DNA. We recently reported that ascorbate (vitamin C) induces Tet-mediated generation of 5hmC. To initially delineate the role of ascorbate on 5hmC generation, we analyzed whether the effect of ascorbate is dependent upon the conditions of other components involved in the hydroxylation of 5mC catalyzed by Tet. We found that removing iron from the culture medium did not affect the induction of 5hmC by ascorbate (10 µM) in mouse embryonic fibroblasts (MEFs). The effect of ascorbate did not involve an increased expression of Tet1-3 or isocitrate dehydrogenases (IDH1-2), the enzymes responsible for producing 2OG. Interestingly, MEFs cultured with different concentrations of glucose, a major precursor of 2OG, exhibited nearly identical responses to ascorbate treatment. Further, blocking the uptake of the reduced form of vitamin C, ascorbic acid, through the sodium-dependent vitamin C transporters (SVCTs) inhibited the effect of ascorbate on 5hmC. However, inhibition of the facilitative glucose transporters (GLUTs), which mediate the incorporation of the oxidized form of vitamin C, dehydroascorbic acid (DHA), did not modify the ability of ascorbate to induce 5hmC generation. These results indicate that the effect of ascorbate on 5hmC is not dependent upon iron uptake, the expression of Tet and IDH, or the production of 2OG, suggesting that ascorbate may directly participate in the generation of 5hmC, most likely as a cofactor of Tet.