Making a Painless Drain: Proof of Concept.

Chest tubes account for a large proportion of postoperative pain after cardiothoracic operations. The objective of this study was to develop a novel, cost-effective, easy-to-use, lidocaine-eluting coating to reduce pain associated with postoperative chest tubes. A lidocaine-eluting hydrogel was developed by dispersing lidocaine-loaded nanoparticles in an aqueous solution containing gelatin (5%). Glutaraldehyde (1%) was added to crosslink the gelatin into a hydrogel. The hydrogel was dehydrated, resulting in a thin, stable polymer. Sterile lidocaine hydrogel-coated silicone discs and control discs were prepared and surgically implanted in the subcutaneous space of C57B6 mice. Using von Frey filaments, mice underwent preoperative baseline pain testing, followed by pain testing on post-procedure day 1 and 3. On post-procedure day 1, mice implanted with control discs demonstrated no change in pain tolerance compared to baseline, while mice implanted with 20 mg and 80 mg lidocaine-loaded discs demonstrated a 2.4-fold (P = 0.36) and 4.7-fold (P = 0.01) increase in pain tolerance, respectively. On post-procedure day 3, mice implanted with control discs demonstrated a 0.7-fold decrease in pain tolerance compared to baseline, while mice implanted with 20 mg and 80 mg lidocaine-loaded discs demonstrated a 1.8-fold (P = 0.88) and 8.4-fold (P = 0.02) increase in pain tolerance, respectively. Our results demonstrate successful development of a lidocaine-eluting chest tube with hydrogel coating, leading to improved pain tolerance in vivo. The concept of a drug-eluting drain coating has significant importance due to its potential universal application in a variety of drain types and insertion locations.

Introduction of robotic surgery does not negatively affect cardiothoracic surgery resident experience.

The objective of this study was to evaluate the educational impact following the implementation of a robotic thoracic surgery program on cardiothoracic (CT) surgery trainees. We hypothesized that the introduction of a robotic thoracic surgery program would adversely affect the CT surgery resident experience, decreasing operative involvement and subsequent competency of surgical procedures. CT surgery residents and thoracic surgery attendings from a single academic institution were administered a recurring, electronic survey from September 2019 to September 2020 following each robotic thoracic surgery case. Surveys evaluated resident involvement and operative performance. This study was exempt from review by our Institutional Review Board. Attendings and residents completed surveys for 86 and 75 cases, respectively. Residents performed > 50% of the operation independently at the surgeon console in 66.2 and 73.3% of cases according to attending and resident responses, respectively. The proportion of trainees able to perform > 75% of the operation increased with each increasing year in training (p = 0.002). Based on the Global Evaluative Assessment of Robotic Skills grading tool, third-year residents averaged higher scores compared to first-year residents (22.9 versus 17.4 out of 30 possible points, p < 0.001), indicating that more extensive prior operative experience could shorten the learning curve of robotic thoracic surgery. CT surgery residents remain actively involved in an operative role during the establishment of a robotic thoracic surgery program. The transition to a robotic thoracic surgery platform appears feasible in a large academic setting without jeopardizing the educational experience of resident trainees.

Introduction of robotic surgery leads to increased rate of segmentectomy in patients with lung cancer.

BACKGROUND: Pulmonary segmentectomy provides an anatomic lung resection while avoiding removal of excess normal lung tissue. This may be beneficial in patients with minimal pulmonary reserve who present with early-stage non-small cell lung cancer (NSCLC). However, the operative performance of a segmentectomy using a video-assisted thoracoscopic approach can be technically challenging. We hypothesized that introduction of the robotic surgical system would facilitate the performance of a segmentectomy as measured by an increase in the proportion of segmentectomies being pursued. METHODS: We completed a retrospective analysis of thoracoscopic and robotic anatomic lung resections, including lobectomies and segmentectomies, performed in patients with primary lung cancer from the time of initiation of the robotic thoracic surgery program in November 2017 to November 2019. We compared the proportion of thoracoscopic and robotic segmentectomies performed during the first year compared to the second year of the data collection period. RESULTS: A total of 138 thoracoscopic and robotic anatomic lung resections were performed for primary lung cancer. Types of lung cancer resected (adenocarcinoma, squamous cell carcinoma, or other), tumor size based on clinical T staging (T1-T4), and tumor location were not significantly different between years (P=0.44, P=0.98, and P=0.26, respectively). The proportion of segmentectomies increased from 8.6% during the first year to 25.0% during the second year (P=0.01). One out of 6 (16.7%) segmentectomies were performed using the robot during the first year versus 15 out of 17 (88.2%) during the second year (P=0.003). CONCLUSIONS: Use of the robot led to a significant increase in the number of segmentectomies performed in patients undergoing anatomic lung resection. With increasing lung cancer awareness and widely available screening, a greater number of small, early-stage tumors suitable for segmentectomy will likely be detected. We conclude that robotic-assisted surgery may facilitate the challenges of performing a minimally invasive segmentectomy.

Secretory Phospholipase A2 IIa Mediates Expression of Growth Factor Receptors in Esophageal Adenocarcinoma.

BACKGROUND: Receptor tyrosine kinases of the epidermal growth factor receptor (EGFR) family such as human epidermal receptor-2 (HER2) are involved in the development and progression of esophageal adenocarcinoma (EAC). Prior studies have demonstrated that group IIa secretory phospholipase A2 (sPLA2 IIa) can function as a ligand for the EGFR family of receptors and lead to an increase in receptor signaling. AIMS: We hypothesized that sPLA2 IIa inhibition downregulates the expression of EGFR and HER-2 in EAC and through this mechanism decreases proliferation in EAC. METHODS: Normal human esophageal epithelium, Barrett's esophagus (BE), and EAC tissue samples were assayed for baseline expression of EGFR, HER-2, and sPLA2 IIa. sPLA2 IIa was attenuated via inhibitor or lentiviral knockdown in esophageal cell lines, and cells were assayed for EGFR and HER2 expression as well as proliferation. FLO1 EAC cells were injected into the flank of nude mice. After randomization, mice received daily group IIA sPLA2 inhibitor or a control solution, and tumor volume was measured with calipers. RESULTS: sPLA2 IIa, EGFR, and HER2 expression increased across the spectrum of normal esophageal epithelium to EAC. sPLA2 IIa inhibition and knockdown decreased the expression of HER-2 and EGFR and proliferation. Mice treated with sPLA2 IIa inhibitor had smaller tumors than controls. CONCLUSIONS: sPLA2 IIa inhibition decreases EGFR and HER2 expression and lowers proliferation of human EAC. The discovery of sPLA2 IIa inhibition's ability to attenuate growth factor receptor signaling underscores the exciting potential of sPLA2 IIa inhibitors as therapeutics in the treatment of EAC.

Statins Inhibit Toll-Like Receptor 4-Mediated Growth of Human Esophageal Adenocarcinoma Cells.

BACKGROUND: Esophageal adenocarcinoma (EAC) is a lethal malignancy with poor prognosis. Pharmacologic inhibitors of inflammation, such as statins, have been shown to decrease the risk of development and progression of esophageal cancer, but the mechanism of this protection is unclear. The objective of this study was to elucidate the effect of statins on toll-like receptor 4-mediated-proliferation of human EAC cells and identify the mechanism responsible for these observed effects. METHODS: Human EAC cells (OE33 and FLO1) were treated with simvastatin or atorvastatin for increasing doses and time periods. Toll-like receptor 4 (TLR4) expression was assessed. Cells were pretreated with statin followed by lipopolysaccharide (LPS). Cell proliferation and expression of signaling proteins were evaluated. FLO1 cells were injected into the flank of nude mice. Mice received intraperitoneal injections of simvastatin, atorvastatin, or control solution and tumor volume was measured. RESULTS: OE33 and FLO1 cells demonstrated decreased TLR4 expression after treatment with simvastatin or atorvastatin for 8 h (P < 0.05). LPS increased proliferation, whereas pretreatment with statin abolished this response (P < 0.05). Statins decreased expression and activation of LPS-induced signaling proteins, including MyD88, TRAF6, Akt, and NF-κB (P < 0.05). Mice receiving daily statin injections demonstrated smaller tumors than control mice (P < 0.001 at day 33). CONCLUSIONS: Treatment of EAC cells with simvastatin or atorvastatin decreases TLR4-mediated proliferation and in vivo tumor growth. Decreased TLR4 expression and subsequent reduction in MyD88-dependent signaling could be a mechanism by which statins act to reduce tumor growth rates.

Outcomes After Converted Minimally Invasive to Open Esophagectomy in Patients With Esophageal Cancer.

BACKGROUND: The objective of this study was to evaluate the impact of unplanned conversion to open esophagectomy during minimally invasive esophagectomy (MIE) on postoperative morbidity and mortality for patients with esophageal cancer, as well as to evaluate the variables that influence the need for conversion. METHODS: This study was a retrospective analysis of patients with esophageal cancer who underwent open esophagectomy or MIE by either a laparothoracoscopic approach or a robotic approach from 2016 to 2018 by using the esophagectomy-specific American College of Surgeons (ACS) National Surgical Quality Improvement Program (NSQIP) database. Poisson regression models were used to analyze 30-day outcomes and risk factors for conversion to open esophagectomy during attempted MIE. RESULTS: A total of 2616 patients were identified. The overall conversion rate for MIE was 6.3%. Compared with completed MIE, patients requiring conversion to open esophagectomy had a significantly increased risk of 30-day mortality (risk ratio, 2.63; 95% confidence interval, 1.03 to 6.69) and experienced a variety of other postoperative complications. Patients requiring conversion to open esophagectomy during MIE also experienced worse perioperative outcomes when compared to patients who underwent planned open esophagectomy. Estimated surgical risk on the basis of the ACS NSQIP Surgical Risk Calculator was the only variable found to be independently associated with conversion from minimally invasive to open esophagectomy (risk ratio, 1.03; 95% confidence interval, 1.01 to 1.04, for each 10% increase in risk score). CONCLUSIONS: Unplanned conversion to open esophagectomy during MIE is associated with significantly greater morbidity and a 2.6-fold increased risk of death when compared with both completed MIE and planned open esophagectomy. The ACS NSQIP Surgical Risk Calculator may help identify patients preoperatively who are at higher risk for conversion to open esophagectomy during MIE.

Secretory Phospholipase A2 Inhibition Attenuates Adhesive Properties of Esophageal Barrett's Cells.

BACKGROUND: Gastroesophageal reflux and Barrett's esophagus are significant risk factors for the development of esophageal adenocarcinoma. Group IIa secretory phospholipase A2 (sPLA2) catalyzes the production of various proinflammatory metabolites and plays a critical role in promoting reflux-induced inflammatory changes within the distal esophagus. We hypothesized that inhibition of sPLA2 in human Barrett's cells would attenuate adhesion molecule expression via decreased activation of nuclear factor kappa B (NF-κB) and decrease cell proliferation, possibly mitigating the invasive potential of Barrett's esophagus. MATERIALS AND METHODS: Normal human esophageal epithelial cells (HET1A) and Barrett's cells (CPB) were assayed for baseline sPLA2 expression. CPB cells were treated with a specific inhibitor of sPLA2 followed by tumor necrosis factor-α. Protein expression was evaluated using immunoblotting. Cell proliferation was assessed using an MTS cell proliferation assay kit. Statistical analysis was performed using the Student's t-test or analysis of variance, where appropriate. RESULTS: CPB cells demonstrated higher baseline sPLA2 expression than HET1A cells (P = 0.0005). Treatment with 30 µM sPLA2 inhibitor significantly attenuated intercellular adhesion molecule-1 (P = 0.004) and vascular cell adhesion molecule-1 (P < 0.0001) expression as well as decreased NF-κB activation (P = 0.002). sPLA2 inhibition decreased cell proliferation in a dose-dependent manner (P < 0.001 for 15, 20, and 30 µM doses). CONCLUSIONS: sPLA2 inhibition in human Barrett's cells decreases cellular adhesive properties and NF-κB activation as well as decreases cell proliferation, signifying downregulation of the inflammatory response and possible attenuation of cellular malignant potential. These findings identify sPLA2 inhibition as a potential chemopreventive target for premalignant lesions of the esophagus.

A Comparison of Frailty Measures at Listing to Predict Outcomes After Lung Transplantation.

BACKGROUND: Sarcopenia may be an important predictive factor of outcomes after lung transplantation (LTx). Serum albumin and the 6-minute walk distance (6MWD) have been shown to be a marker of LTx outcomes. We measured sarcopenia, albumin, and 6MWD in a cohort of LTx patients and analyzed the utility of these as markers of outcomes for LTx patients. METHODS: We retrospectively identified LTx recipients from 2013-2018 at our institution who underwent computed tomographic imaging during their listing evaluation. From that image, we measured skeletal muscle cross-sectional surface area at the third lumbar vertebral level, and sarcopenia was diagnosed by established cutoffs. Associations between sarcopenia, albumin, 6MWD, and survival, and hospital length of stay, complications, readmissions, and discharge destination were evaluated. RESULTS: Sarcopenia was found in 72% (95 of 132) of patients, 18% (24 of 131) of patients were hypoalbuminemic, and 41% had a low 6MWD. Survival was not associated with presence of sarcopenia (hazard ratio [HR], 1.06; 95% confidence interval [CI], 0.46-2.42) or low 6MWD (HR, 0.86; 95% CI, 0.410-1.83). Hospital length of stay, complications, readmissions, and discharge destination were not influenced by sarcopenia or 6MWD. In contrast, hypoalbuminemia was independently associated with decreased survival (HR, 2.25; 95% CI, 1.04-4.85) and a higher grade of postoperative complications (P = .04). CONCLUSIONS: Sarcopenia is prevalent in LTx patients. Neither sarcopenia nor 6MWD predicted mortality or short-term outcomes after LTx. This is in contrast to albumin levels, which were inversely associated with survival and complications. Albumin shows promise as an important predictor of mortality and short-term outcomes after LTx.