Robotic hiatal hernia repair without mesh.

Background: Newer minimally invasive techniques have supplanted laparotomy and thoracotomy for management of hiatal hernias. Limited data exists on outcomes after robotic hiatal hernia repair without mesh despite the increasing popularity of this approach. We report our high-volume experience with durable robotic hiatal hernia repair with gastric fundoplication without mesh. Methods: A retrospective review was conducted on patients with type I-IV hiatal hernias who underwent an elective robotic-assisted repair from 2016 to 2019 using a novel technique of approximating the hiatus with running barbed absorbable (V-locTM) suture and securing it with interrupted silk sutures. Main outcomes included length of stay, readmission rate, and recurrence rate. Results: A total of 144 patients were reviewed. The average age of the patient was 61 years. Most of the patients were female [95 females (66%) to 49 males], and the average body mass index (BMI) was 29.96 kg/m2. The average operating time was 173 minutes (standard deviation 62 minutes). The average length of stay in the hospital was 2 days, and 89% of patients went home within the first 3 days. Ten patients (6.9%) were readmitted within 30 days, there were no mortalities in 30 days, and there were 6 (4.2%) recurrences on follow up requiring reoperation. Conclusions: Elective robotic hiatal hernia repair with fundoplication and primary closure of the hiatus with V-locTM and nonabsorbable suture without mesh is safe and effective. The robotic approach has similar operative times, lengths of stay, and complications compared to nationally published data on laparoscopic hiatal hernia repairs.

Pancoast tumor: a modern perspective on an old problem.

PURPOSE OF REVIEW: Pancoast tumors, also known as superior sulcus tumors, to this day remain a complex and challenging condition. This review will explore the evolution of the treatment of these tumors over the better part of a century. It will illustrate how with a multidisciplinary approach and the use of trimodality therapy this entity has evolved from a universally fatal disease to one that is treatable with outcomes similar to those of other stage-matched nonsmall cell lung cancers. RECENT FINDINGS: The Southwest Oncology Group 9416 Intergroup 0160 trial reported in 2007 By Rusch et al. culminated years of research showing that trimodality therapy with chemotherapy, radiation and surgery provided optimal outcomes. Since that time, there have been studies corroborating these outcomes and utilization of novel surgical approaches including Video-assisted thoracoscopic surgery; however, no change in survival has been reported. SUMMARY: The treatment of tumors of the superior sulcus has evolved over the years, so that outcomes approach those of other stage-matched nonsmall cell carcinomas. In the future, new approaches, perhaps the detailed genetic analysis of tumors and guided treatments, will have a positive impact on nonsmall cell carcinomas. The tumors of the superior sulcus will hopefully follow suit in their improved outcomes.

Impact That Day of the Week has on Length of Stay for Video-assisted Lobectomy.

We aimed to analyze the effect that the day of the week for video-assisted thoracoscopic surgery lobectomy has on length of stay . A retrospective review identified all patients who underwent video-assisted thoracoscopic surgery lobectomy at a single institution from January 2016 to July 2017. In total, 208 patients were divided into 2 groups based on timing of their operation: Operations performed on Monday, Tuesday, or Wednesday were defined as "early in the week" and those performed on Thursday or Friday were defined as "late in the week." We then propensity-matched 81 pairs of patients and analyzed perioperative data and short-term clinical outcomes. A total of 208 patients underwent video-assisted thoracic surgery lobectomy during the study period. Length of stay was significantly decreased by 2.0 days (P <0.0001) for all lobectomies performed "early in the week" compared with those performed "late in the week." Thirty-day mortality and all major morbidities did not significantly different between the 2 matched groups. Our findings suggest that major pulmonary resections should be performed early in the week, when feasible, to facilitate utilization of hospital resources and prompt discharge.

Uniportal VATS Lobectomy and Decortication: Not an Everyday Occurrence.

Management of trapped lung with an underlying lung lesion and hydropneumothorax remains controversial. Furthermore, Aspergillus empyema and aspergilloma are rare pathologies for which uniportal video-assisted thoracoscopic (VATS) surgical management remains controversial. We present a young patient referred to our service after recent hospitalization for pneumonia. The patient was found to have a chronic effusion with a right lower lobe cystic parenchymal lesion and was taken to the operating room. The patient underwent right uniportal VATS surgery with evacuation of empyema, total pulmonary decortication, and right lower lobectomy. His postoperative course was unremarkable, and he was discharged home. Postoperative workup demonstrated lymphocyte variant hypereosinophilia. He continues to follow with thoracic surgery at the time of this report and remains asymptomatic. We conclude that uniportal VATS is a most minimally invasive, safe, and efficient approach for management of complex intrathoracic pathology including total pulmonary decortication and lobectomy.

An epigenetic switch regulates the ontogeny of AXL-positive/EGFR-TKi-resistant cells by modulating miR-335 expression.

Despite current advancements in research and therapeutics, lung cancer remains the leading cause of cancer-related mortality worldwide. This is mainly due to the resistance that patients develop against chemotherapeutic agents over the course of treatment. In the context of non-small cell lung cancers (NSCLC) harboring EGFR-oncogenic mutations, augmented levels of AXL and GAS6 have been found to drive resistance to EGFR tyrosine kinase inhibitors such as Erlotinib and Osimertinib in certain tumors with mesenchymal-like features. By studying the ontogeny of AXL-positive cells, we have identified a novel non-genetic mechanism of drug resistance based on cell-state transition. We demonstrate that AXL-positive cells are already present as a subpopulation of cancer cells in Erlotinib-naïve tumors and tumor-derived cell lines and that the expression of AXL is regulated through a stochastic mechanism centered on the epigenetic regulation of miR-335. The existence of a cell-intrinsic program through which AXL-positive/Erlotinib-resistant cells emerge infers the need of treating tumors harboring EGFR-oncogenic mutations upfront with combinatorial treatments targeting both AXL-negative and AXL-positive cancer cells.

Robotic-Assisted First Rib Resection: Our Experience and Review of the Literature.

Thoracic outlet syndrome (TOS) comprises a constellation of signs and symptoms that arise from neurologic and vascular compression of the brachial plexus and subclavian vasculature, respectively. Surgical decompression of the neurovascular structures is often indicated to alleviate TOS. We report here our robotic surgical approach and experience for resection of the first rib. Between July 2014 and January 2017, 17 patients who underwent robotic-assisted first rib resection at our institution were reviewed. Nine women and 8 men with a mean age of 45 ± 11 years had a robotic-assisted first rib resection; 8 for neurogenic TOS and 9 for venous TOS. There were no complications or conversion to open surgery. The mean operative time was 113.2 ± 55.3 minutes. Length of stay was a mean of 1.8 ± 1.9 days. Length of rib resected was 5.8 ± 0.5 cm. Anticoagulation for the venous TOS cohort was Xarelto, for a mean of 5.1 ± 1.8 months. Short-term follow-up (mean 10.3 ± 4.9 days) revealed resolution of symptoms in all patients, with patent vasculature on venogram for the entire venous TOS cohort. Further follow-up at 2 months and 6 months revealed that all patients remained symptom free. Based on our institution's experience with the robotic-assisted approach to first rib resection, we feel that it is a feasible approach that could be added to the armamentarium of the thoracic surgeon.

Intermediate oncologic outcomes after uniportal video-assisted thoracoscopic thymectomy for early-stage thymoma.

BACKGROUND: Recent years have seen a trend towards utilizing a video-assisted thoracic surgery (VATS) approach for treatment of thymoma. Although increasing in practice, intermediate- and long-term oncologic outcome data is lacking for the VATS approach. There is no oncologic data for the uniportal VATS approach. We sought to evaluate the feasibility and impact on patient survival of uniportal VATS thymectomy for early-stage thymoma. METHOD: The clinical outcomes for 17 patients with Masaoka stage I to II thymomas treated between January of 2009 and July of 2014 at a single institution were collected retrospectively. Primary endpoint was overall survival (OS) and secondary endpoint was recurrence-free survival (RFS). RESULTS: Ten women and seven men underwent uniportal VATS thymectomy; eleven had stage I thymoma and six had stage II thymoma. There were no conversions to open surgery. Operative mortality was zero. Mean tumor size was 3.8±1.0 centimeters, with a range of 1.9 to 6.0 centimeters. All patients underwent a R0 resection. Five-year survival was 100%, and the estimated RFS was 100%. CONCLUSIONS: Our findings suggest that uniportal VATS thymectomy for early-stage thymoma is feasible, and the intermediate-term oncologic outcomes are comparable to historic standards for open and multi-incision VATS thymectomy. However, additional follow-up is required to evaluate for long-term oncologic outcomes.

Switching from Thoracoscopic to Robotic Platform for Lobectomy: Report of Learning Curve and Outcome.

OBJECTIVE: The optimal minimally invasive surgical management for patients with non-small-cell lung cancer (NSCLC) is unclear. For experienced video-assisted thoracoscopic surgery (VATS) surgeons, the increased costs and learning curve are strong barriers for adoption of robotics. We examined the learning curve and outcome of an experienced VATS lobectomy surgeon switching to a robotic platform. METHODS: We conducted a retrospective review to identify patients who underwent a robotic or VATS lobectomy for NSCLC from 2016 to 2018. Analysis of patient demographics, perioperative data, pathological upstaging rates, and robotic approach (RA) learning curve was performed. RESULTS: This study evaluated 167 lobectomies in total, 118 by RA and 49 by VATS. Patient and tumor characteristics were similar. RA had significantly more lymph node harvested (14 versus 10; P = 0.004), more nodal stations sampled (5 versus 4; P < 0.001), and more N1 nodes (8 versus 6; P = 0.010) and N2 nodes (6 versus 4; P = 0.017) resected. With RA, 22 patients were upstaged (18.6%) compared to 5 patients (10.2%) with VATS (P = 0.26). No differences were found in perioperative outcome. Operative time decreased significantly with a learning curve of 20 cases, along with a steady increase in lymph node yield. CONCLUSIONS: RA can be adopted safely by experienced VATS surgeons. Learning curve is 20 cases, with RA resulting in superior lymph node clearance compared to VATS. The potential improvement in upstaging and oncologic resection for NSCLC may justify the associated investments of robotics even for experienced VATS surgeons.

Vein graft arterialization causes differential activation of mitogen-activated protein kinases.

OBJECTIVE: Vascular injury results in activation of the mitogen-activated protein kinases-extracellular-signal regulated kinases, c-jun N-terminal kinase, and p38(MAPK)-which have been implicated in cell proliferation, migration, and apoptosis. The goal of this study was to characterize mitogen-activated protein kinase activation in arterialized vein grafts. METHODS: Carotid artery bypass using reversed external jugular vein was performed in 29 dogs. Vein grafts were harvested after 30 minutes and 3, 8, and 24 hours, and 4, 7, 14, and 28 days. Contralateral external jugular vein and external jugular vein interposition vein-to-vein grafts were used as controls. Vein graft extracts were analyzed for extracellular-signal regulated kinases, c-jun N-terminal kinase, and p38(MAPK) activation. Proliferating cell nuclear antigen expression was investigated as a parameter of cell proliferation. Apoptosis was assessed by terminal deoxynucleotidyl transferase-mediated 2'-deoxyuridine 5'-triphosphate nick end labeling staining and intimal hyperplasia by morphometric examination of tissue sections. RESULTS: Significant intimal hyperplasia was observed at 28 days. Over the time points studied, vein graft arterialization resulted in bimodal activation of both extracellular-signal regulated kinase and p38(MAPK) (30 minutes through 3 hours; 4 days) but did not induce activation of c-jun N-terminal kinase. Proliferating cell nuclear antigen expression increased from days 1 through 28, and apoptosis increased between 8 and 24 hours. CONCLUSION: Vein graft arterialization induces bimodal activation of extracellular-signal regulated kinase and p38(MAPK); however, in contrast with what is described in arterial injury, it does not induce c-jun N-terminal kinase activation. These results provide the first comprehensive characterization of the mitogen-activated protein kinase signaling pathways activated in vein graft arterialization and identify mitogen-activated protein kinases as potential mediators of vein graft remodeling and subsequent intimal hyperplasia.

Activation of mitogen-activated protein kinases during preparation of vein grafts and modulation by a synthetic inhibitor.

OBJECTIVE: Long-term durability of saphenous vein grafts used for coronary artery bypass grafting is limited by neointimal formation. Arterial vascular injury is known to activate intracellular mitogen-activated protein kinases, including extracellular signal-regulated kinases and c-jun N-terminal kinases, that affect cell differentiation, proliferation, migration, and apoptosis. This study tests the hypothesis that these mitogen-activated protein kinases are activated in saphenous veins during preparation for coronary artery bypass grafting. METHODS: Saphenous veins were harvested from 10 patients undergoing coronary artery bypass grafting. A specimen from each vein was placed in ice-cold lysis buffer immediately after harvesting (t = 0). The remaining tissue was incubated at room temperature in normal saline, 0.1% dimethylsulfoxide (vehicle), or 50 mmol/L PD98059 (mitogen-activated protein kinase kinase-1/2 inhibitor) until the vein was grafted (mean 50 minutes). To study kinetics of intracellular signaling pathways, canine saphenous veins were harvested, and mitogen-activated protein kinases and PI-3 kinase pathways were studied after different incubation time intervals. Extracted proteins were analyzed by Western blotting or in vitro kinase assay. RESULTS: The human saphenous veins showed elevated levels of active extracellular signal-regulated kinase after harvesting (t = 0) and prior to implant (t = 1). Incubation with PD98059 resulted in decreased activation of extracellular signal-regulated kinase. Kinetics of canine saphenous veins showed extracellular signal-regulated kinase and c-jun N-terminal kinase activation, in a time-dependent manner, along with activation of the growth factor-regulated PI3 kinase pathway. CONCLUSIONS: This study characterizes activation of extracellular signal-regulated kinases and c-jun N-terminal kinases during vein graft preparation and demonstrates the ability to inhibit extracellular signal-regulated kinase activation by simple incubation with a specific inhibitor. Further studies are needed to evaluate the significance of these findings with respect to graft durability.

Transforming growth factor-beta1 induces apoptosis in vascular endothelial cells by activation of mitogen-activated protein kinase.

BACKGROUND: Vascular endothelial cell apoptosis is central in atherosclerosis and intimal hyperplasia. Transforming growth factor (TGF)-beta1 induces endothelial cell apoptosis through unidentified mechanism(s). Although TGF-beta1 signals through the Smad proteins, in some nonendothelial cell types it also activates the mitogen-activated protein kinase (MAPK) (extracellular signal-regulated kinase, c-Jun N-terminal kinase, and p38 MAPK [p38(MAPK)]). p38(MAPK) relays apoptotic signals in several cell types. We hypothesized that TGF-beta1 activates endothelial cell MAPKs and induces apoptosis through p38(MAPK) activation. METHODS: Human umbilical vein or bovine capillary endothelial cells were incubated with TGF-beta1 for 0.5 to 12 hours. MAPK activation was characterized by Western blotting with antibodies to phosphorylated extracellular signal-regulated kinase 1/2, p38(MAPK), or c-Jun N-terminal kinases 1/2. To study apoptosis, extracts of cells incubated with TGF-beta1 for 6 hours with or without MAPK inhibitors were characterized by Western blotting analysis of poly (ADP-Ribose) polymerase degradation. RESULTS: TGF-beta1 induced p38(MAPK), extracellular signal-regulated kinase 1/2, and c-Jun N-terminal kinase 1/2 activation and increased apoptosis. Inhibition of p38(MAPK) significantly reduced TGF-beta1-induced apoptosis. In contrast, inhibition of other signaling pathways was ineffective. CONCLUSIONS: TGF-beta1 induces endothelial cell apoptosis through p38(MAPK) activation. Because TGF-beta1 is upregulated in vascular remodeling, p38(MAPK) is a potential target to prevent endothelial cell apoptosis during this process.

Metastatic meningioma extending into the left atrium through the pulmonary vein.

Left atrial extension of pulmonary tumors through the pulmonary vein is most often associated with primary malignancies and is rarely associated with metastatic disease. We present the first, to our knowledge, reported case of a patient with a history of intracranial meningioma resections presenting with metastatic meningioma to the right lower lobe with extension into the left atrium through the pulmonary vein.

Electromagnetic navigational bronchoscopy: a surgeon's perspective.

Diagnostic yield of flexible bronchoscopy is often limited by the size and location of the lesion of interest. Novel technologies have evolved that can improve the accuracy and expand the applicability of flexible bronchoscopy in rendering a tissue diagnosis for pulmonary nodules. One recent technical advance uses electromagnetic guidance to improve the ability of the bronchoscopist to navigate within the lung parenchyma as well as to localize and biopsy mediastinal pathology. We have gained a preliminary experience with navigational bronchoscopy using electromagnetic guidance to successfully biopsy peripheral lung lesions, place fiducial catheters to aid stereotactic radiotherapy, and to biopsy mediastinal lymph nodes in the staging of lung cancer. Not only will navigational bronchoscopy lead to improvements in the diagnostic yield of standard flexible bronchoscopy, but we envision potential therapeutic modalities that can be used this system.

VEGF, a prosurvival factor, acts in concert with TGF-beta1 to induce endothelial cell apoptosis.

VEGF and TGF-beta1 are potent angiogenesis inducers with opposing effects on endothelial cells. TGF-beta1 induces apoptosis; VEGF protects endothelial cells from apoptosis. We found that TGF-beta1 promotes endothelial cell expression of FGF-2, which up-regulates VEGF synthesis. Inhibition of VEGF signaling through VEGF receptor 2 (flk-1) abrogates TGF-beta1-induced apoptosis and p38(MAPK) activation. Inhibition of p38(MAPK) blocks TGF-beta1-induced apoptosis, showing that VEGF/flk-1-mediated activation of p38(MAPK) is required for TGF-beta1 induction of apoptosis. In the absence of TGF-beta1, VEGF activates p38(MAPK) and promotes endothelial cell survival. However, in context with TGF-beta1, VEGF/flk-1-mediated activation of p38(MAPK) results in apoptosis. Thus, cross-talk between TGF-beta1 and VEGF signaling converts VEGF/flk-1-activated p38(MAPK) into a proapoptotic signal. This finding illustrates an unexpected role of VEGF and indicates that VEGF can be pharmacologically converted into an apoptotic factor, a novel approach to antiangiogenesis therapy.

Bone marrow-derived cells contribute to epithelial engraftment during wound healing.

Recent findings suggest that bone marrow-derived cells (BMDC) may contribute to tissue maintenance throughout the body. However, it is not yet known whether marrow-derived epithelial cells are capable of undergoing proliferation. Our laboratory has shown that BMDC engraft as keratinocytes in the skin at low levels (