Consequences of anastomotic leaks after minimally invasive esophagectomy: A single-center experience.

Background: Anastomotic leak (AL) after minimally invasive esophagectomy (MIE) is a well-described source of morbidity for patients undergoing surgical treatment of esophageal neoplasm. With improved early recognition and endoscopic management techniques, the long-term impact remains unclear. Methods: A retrospective review was conducted of patients who underwent MIE for esophageal neoplasm between January 2015 and June 2021 at a single institution. Cohorts were stratified by development of AL and subsequent management. Baseline demographics, perioperative data, and post-operative outcomes were examined. Results: During this period, 172 MIEs were performed, with 35 of 172 (20.3%) complicated by an AL. Perioperative factors independently associated with AL were post-operative blood transfusion (leak rate 52.9% versus 16.8%; p = 0.0017), incompleteness of anastomotic rings (75.0% vs 19.1%; p = 0.027), and receiving neoadjuvant therapy (18.5% vs 30.8%; p < 0.0001). Inferior short-term outcomes associated with AL included number of esophageal dilations in the first post-operative year (1.40 vs 0.46, p = 0.0397), discharge disposition to a location other than home (22.9% vs 8.8%, p = 0.012), length of hospital stay (17.7 days vs 9.6 days; p = 0.002), and time until jejunostomy tube removal (134 days vs 79 days; p = 0.0023). There was no significant difference in overall survival between patients with or without an AL at 1 year (79% vs 83%) or 5 years (50% vs 47%) (overall log rank p = 0.758). Conclusions: In this large single-center series of MIEs, AL was associated with inferior short-term outcomes including hospital length of stay, discharge disposition other than to home, and need for additional endoscopic procedures, without an accompanying impact on 1-year or 5-year survival. Key message: In this large, single-center series of minimally invasive esophagectomies, anastomotic leak was associated with worse short-term outcomes including hospital length of stay, discharge disposition other than to home, and need for additional endoscopic procedures, but was not associated with worse long-term survival. The significant association between neoadjuvant therapy and decreased leak rates is difficult to interpret, given the potential for confounding factors, thus careful attention to modifiable pre- and peri-operative patient factors associated with anastomotic leak is warranted.

Microfluidics in vascular biology research: a critical review for engineers, biologists, and clinicians.

Neovascularization, the formation of new blood vessels, has received much research attention due to its implications for physiological processes and diseases. Most studies using traditional in vitro and in vivo platforms find challenges in recapitulating key cellular and mechanical cues of the neovascularization processes. Microfluidic in vitro models have been presented as an alternative to these limitations due to their capacity to leverage microscale physics to control cell organization and integrate biochemical and mechanical cues, such as shear stress, cell-cell interactions, or nutrient gradients, making them an ideal option for recapitulating organ physiology. Much has been written about the use of microfluidics in vascular biology models from an engineering perspective. However, a review introducing the different models, components and progress for new potential adopters of these technologies was absent in the literature. Therefore, this paper aims to approach the use of microfluidic technologies in vascular biology from a perspective of biological hallmarks to be studied and written for a wide audience ranging from clinicians to engineers. Here we review applications of microfluidics in vascular biology research, starting with design considerations and fabrication techniques. After that, we review the state of the art in recapitulating angiogenesis and vasculogenesis, according to the hallmarks recapitulated and complexity of the models. Finally, we discuss emerging research areas in neovascularization, such as drug discovery, and potential future directions.

In search of constrained FTY720 and phytosphingosine analogs as dual acting anticancer agents targeting metabolic and epigenetic pathways.

A series of compounds containing pyrrolidine and pyrrolizidine cores with appended hydrophobic substituents were prepared as constrained analogs of FTY720 and phytosphingosine. The effect of these compounds on the viability of cancer cells, on downregulation of the nutrient transport systems, and on their ability to cause vacuolation was studied. An attempt to inhibit HDACs with some phosphate esters of our analogs was thwarted by our failure to reproduce the reported inhibitory action of FTY720-phosphate.

Effects of stereochemistry, saturation, and hydrocarbon chain length on the ability of synthetic constrained azacyclic sphingolipids to trigger nutrient transporter down-regulation, vacuolation, and cell death.

Constrained analogs containing a 2-hydroxymethylpyrrolidine core of the natural sphingolipids sphingosine, sphinganine, N,N-dimethylsphingosine and N-acetyl variants of sphingosine and sphinganine (C2-ceramide and dihydro-C2-ceramide) were synthesized and evaluated for their ability to down-regulate nutrient transporter proteins and trigger cytoplasmic vacuolation in mammalian cells. In cancer cells, the disruptions in intracellular trafficking produced by these sphingolipids lead to cancer cell death by starvation. Structure activity studies were conducted by varying the length of the hydrocarbon chain, the degree of unsaturation and the presence or absence of an aryl moiety on the appended chains, and stereochemistry at two stereogenic centers. In general, cytotoxicity was positively correlated with nutrient transporter down-regulation and vacuolation. This study was intended to identify structural and functional features in lead compounds that best contribute to potency, and to develop chemical biology tools that could be used to isolate the different protein targets responsible for nutrient transporter loss and cytoplasmic vacuolation. A molecule that produces maximal vacuolation and transporter loss is expected to have the maximal anti-cancer activity and would be a lead compound.