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Purpose: The DNA methylation paradox, manifested as derepression of cancer-testis antigens, and silencing of tumor suppressors during malignant transformation, provides the rationale for the utilization of chromatin remodeling agents for cancer therapy. A phase I trial was done to examine pharmacokinetics, toxicities, and gene expression mediated by 5-aza-2′-deoxycytidine (DAC) in patients with thoracic malignancies.Experimental Design: Thirty-five patients with cancers refractory to standard therapy received continuous 72-hour DAC infusions using a phase I dose-escalation schema. Each full course of therapy consisted of two identical 35-day cycles. Plasma DAC levels were evaluated by liquid chromatography-mass spectrometry techniques. Quantitative reverse transcription-PCR, methylation-specific PCR, and immunohistochemical techniques were used to evaluate NY-ESO-1, MAGE-3, and p16 expression in tumor biopsies. Long oligonucleotide arrays were used to evaluate gene expression profiles in laser-captured tumor cells before and after DAC exposure.Results: Thirty-five patients were evaluable for toxicities; 25 were evaluable for treatment response. Myelosuppression constituted dose-limiting toxicity. The maximum tolerated dose of DAC was 60 to 75 mg/m2 depending on the number of prior cytotoxic chemotherapy regimens. No objective responses were observed. Plasma DAC concentrations approximated thresholds for gene induction in cultured cancer cells. Target gene induction was observed in 36% of patients. Posttreatment antibodies to NY-ESO-1 were detected in three patients exhibiting NY-ESO-1 induction in their tumor tissues. Complex, heterogeneous gene expression profiles were observed in pretreatment and posttreatment tissues.Conclusion: Prolonged DAC infusions can modulate gene expression in primary thoracic malignancies. These findings support further evaluation of DNA-demethylating agents alone or in combination with other regimens targeting induced gene products for the treatment of these neoplasms.

Supplementary Figure 1 from Phase I Study of Decitabine-Mediated Gene Expression in Patients with Cancers Involving the Lungs, Esophagus, or Pleura

Supplementary Table 1 from Phase I Study of Decitabine-Mediated Gene Expression in Patients with Cancers Involving the Lungs, Esophagus, or Pleura

Radium is a significant source of human radiation exposure both from natural sources (NORM, or Naturally Occurring Radioactive Material) and from technologically enhanced natural radioactive material (TENORM). Gamma analysis for 226Ra and 228Ra in water using high purity germanium (HPGe) detectors was compared with current methods from the US Environmental Protection Agency (EPA) using alpha scintillation and gas proportional counters. Extensive evaluations of a modified version of the original Georgia Tech HPGe method were performed. Known value 226Ra samples from the US Department of Energy (DOE) Mixed-Analyte Performance Evaluation Program (MAPEP) program, mixed 226Ra and 228Ra samples from the Environmental Resource Associates Quality Assurance Program (ERA), and mixed 226Ra and 228Ra samples from the Laboratory Proficiency Testing Program of the International Atomic Energy Agency (IAEA) were used for cross-check comparisons of the modified Georgia Tech method with other methodologies (EPA 903.1 and Ra-05 for 226Ra and 228Ra, respectively). Minimum counting times for our gamma instrumentation to reach a minimum detectable activity (MDA) of 0.04 Bq L-1 were also determined.

Objectives To examine how postoperative pain control after robotic thoracoscopic surgery varies with liposomal bupivacaine (LipoB) versus 0.5% bupivacaine/1:200,000 epinephrine (Bupi/Epi) intercostal nerve blocks within the context of an enhanced recovery after thoracic surgery (ERATS) protocol. Design A retrospective analysis of a prospectively maintained database of patients undergoing robotic thoracoscopic procedures between September 1, 2018 and October 31, 2019 was conducted. Setting University of Miami, single-institutional. Participants Patients. Interventions Two hundred fifty-two patients had either LipoB intercostal nerve blocks (n = 129) or Bupi/Epi intercostal nerve blocks (n = 123) when undergoing robotic thoracic surgery. Measurements and Main Results Comparative analysis of patient-reported pain levels, in-hospital and post-discharge opioid requirements, 90-day operative complications, length of hospital stay, and hospital costs was performed. Data were stratified to either anatomic lung resection or pulmonary wedge resection/mediastinal-pleural procedures. Bupi/Epi patients reported significantly more acute postoperative pain than LipoB patients, which correlated with higher in-hospital and post-discharge opioid requirements. There were no differences in postoperative complications, length of hospital stay, or hospital costs between the two groups. Conclusions As part of an ERATS protocol, infiltration of intercostal spaces and surgical wounds with LipoB for robotic thoracoscopic procedures afforded better postoperative subjective pain control and decreased opioid requirements without an increase in hospital costs as compared with use of Bupi/Epi.

BACKGROUND: Enhanced recovery after surgery protocols incorporate evidence-based practices of pre-, intra- and post-operative care to achieve the most optimal surgical outcome, safe on-time discharge, and surgical cost efficiency. Such protocols have been adapted for specialty-specific needs and are implemented by a variety of surgical disciplines including general thoracic surgery. This study aims to evaluate the impact of our enhanced recovery after thoracic surgery (ERATS) protocol on postoperative outcomes, pain, and opioid utilization following thoracotomy. METHODS: This is a retrospective analysis of patients undergoing elective resection of intrathoracic neoplasms via posterolateral thoracotomy between 1/1/2016 and 3/1/2020. Our enhanced recovery protocol, with a focus on multimodal pain management (opioid-sparing analgesics, infiltration of local anesthetics into intercostal spaces and surgical wounds, and elimination of thoracic epidural analgesia) was initiated on 2/1/2018. Demographics, clinicopathology data, subjective pain levels, peri-operative outcomes, in-hospital and post-discharge opioid utilization were obtained from the electronic medical record. RESULTS: A total of 98 patients (43 pre- and 55 post-protocol implementation) were included in this study. There was no difference in perioperative outcomes or percentage of opioid utilization between the two cohorts. The enhanced recovery group had significantly less acute pain. A significant reduction of in-hospital potent schedule II opioid use was noted following ERATS implementation [average MME: 10.5 (3.5–16.5) (ERATS) vs. 19.5 (12.6–36.0) (pre-ERATS), P

To evaluate differences in postoperative pain control and opioids requirement in thoracic surgical patients following implementation of an Enhanced Recovery after Thoracic Surgery protocol with a comprehensive postoperative pain management strategy.A retrospective analysis of a prospectively maintained database of patients undergoing pulmonary resections by robotic thoracoscopy or thoracotomy from January 1, 2017, to January 31, 2019, was conducted. Multimodal pain management strategy (opioid-sparing analgesics, infiltration of liposomal bupivacaine to intercostal spaces and surgical sites, and elimination of thoracic epidural analgesia use in thoracotomy patients) was implemented as part of Enhanced Recovery after Thoracic Surgery on February 1, 2018. Outcome metrics including patient-reported pain levels, in-hospital and postdischarge opioids use, postoperative complications, and length of stay were compared before and after protocol implementation.In total, 310 robotic thoracoscopy and 62 thoracotomy patients met the inclusion criteria. This pain management strategy was associated with significant reduction of postoperative pain in both groups with an overall reduction of postoperative opioids requirement. Median in-hospital opioids use (morphine milligram equivalent per day) was reduced from 30 to 18.36 (P = .009) for the robotic thoracoscopy group and slightly increased from 15.48 to 21.0 (P = .27) in the thoracotomy group. More importantly, median postdischarge opioids prescribed (total morphine milligram equivalent) was significantly reduced from 480.0 to 150.0 (P .001) and 887.5 to 150.0 (P .001) for the thoracoscopy and thoracotomy groups, respectively. Similar short-term perioperative outcomes were observed in both groups before and following protocol implementation.Implementation of Enhanced Recovery after Thoracic Surgery allows safe elimination of epidural use, better pain control, and less postoperative opioids use, especially a drastic reduction of postdischarge opioid need, without adversely affecting outcomes.

ImportanceOutcomes of localized malignant pleural mesothelioma (MPM) remain poor despite multimodality therapy. It is unclear what role disparities have in the overall survival (OS) of patients with operable MPM.ObjectiveTo examine survival disparities associated with social determinants of health (SDOHs) and treatment access in patients with malignant pleural mesothelioma.Design, Setting, and ParticipantsIn this observational, retrospective cohort study, patients with MPM diagnosed between January 1, 2004, and December 31, 2017, were identified from the National Cancer Database with a maximum follow-up time of 13.6 years. The analysis was conducted from February 16, 2022, to July 29, 2022. Patients were included if they were diagnosed with potentially resectable clinical stage I to IIIA MPM, had epithelioid and biphasic histologic subtypes, and received chemotherapy. Patients were excluded if they could not receive curative surgery, were 75 years or older, or had metastasis, unknown stage, or tumor extension to the chest wall, mediastinal tissues, or organs.ExposuresChemotherapy alone vs chemotherapy with curative surgery in the form of pleurectomy and decortication or extrapleural pneumonectomy.Main Outcomes and MeasuresThe primary end point was OS. Cox proportional hazards regression models were used to determine hazard ratios (HRs) for OS, including univariable and multivariable models controlling for potential confounders, including demographic, comorbidity, clinical, treatment, tumor, and hospital-related variables, as well as SDOHs.ResultsA total of 1389 patients with MPM were identified (median [IQR] age, 66 [61-70] years; 1024 [74%] male; 12 [1%] Asian, 49 [3%] Black, 74 [5%] Hispanic, 1233 [89%] White, and 21 [2%] of other race). The median OS was 1.7 years (95% CI, 1.6-1.8). Risk factors associated with worse OS included older age, male sex, Black race, low income, and low educational attainment. Factors associated with greater odds of survival included receipt of surgical therapy, recent year of treatment, increased distance to travel, and treatment at high-volume academic hospitals. The risk factors most strongly associated with poor OS included Black race (HR, 1.96; 95% CI, 1.43-2.69) and male sex (HR, 1.60; 95% CI, 1.38-1.86). Surgical treatment in addition to systemic chemotherapy (HR, 0.70; 95% CI, 0.61-0.81) was independently associated with improved OS, as were chemotherapy initiation (HR, 0.93; 95% CI, 0.87-0.99) and greater travel distance from the hospital (HR, 0.92; 95% CI, 0.86-0.98).Conclusions and RelevanceIn this retrospective cohort study of patients with operable MPM, there was significant variability in access to care by SDOHs. Addressing disparities in access to multimodality therapy can help ensure equity of care for patients with MPM.

Benign vascular tumors of the mediastinum are rare, representing only 0.5% of all mediastinal masses. Given their rare presentation, they are infrequently considered in the workup of a middle mediastinal mass. We present a unique case describing the clinical, imaging and pathologic characteristics of a middle mediastinal cavernous hemangioma which was initially misdiagnosed as a bronchogenic cyst and ultimately required surgical resection with the use of veno-venous extracorporeal membrane oxygenation.

Critical airway stenosis is challenging for surgeons and anesthesiologists to secure a reliable airway for ventilation. The use of venovenous (VV)-extracorporeal membrane oxygenation (ECMO) has been described as a strategy to provide adequate gas exchange in such instances. We present a case of a young female with a complex paratracheal mass significantly compressing the trachea; a planned intraoperative VV-ECMO was instituted to allow safe orotracheal intubation of a double-lumen endotracheal tube for lung isolation and tumor resection.

In the last decade, the implementation of enhanced recovery protocol for patients undergoing thoracic surgical procedures, either by thoracotomy or thoracoscopy, has gained significant recognition. Such protocols have been developed following the enhanced recovery after surgery (ERAS) guiding principles, yet have been tailored with attention to the unique nuances of thoracic surgical patients. Over the last 5 years, a body of literature has been published attesting to the success of the enhanced recovery after thoracic surgery (ERATS) protocol, with reported improvements of measurable outcome metrics. This mini-review focuses on postoperative pain control using the innovative strategy of opioid-sparing multimodal analgesics of the ERATS care pathway.

BACKGROUND: We sought to evaluate trends and clinical and economic outcomes between robotic-assisted lobectomy (RL), video-assisted thoracoscopic lobectomy (VL), and open pulmonary lobectomy (OL). METHODS: Patients who underwent a lobectomy for malignancy from January 1, 2008, to September 30, 2015, were identified in the Premier Healthcare Database. Propensity score matched (PSM) comparisons were performed between RL versus VL and RL versus OL. Patient characteristics were applied to generate propensity scores. In-hospital and perioperative 30-day outcomes and costs were compared within matched cohorts. RESULTS: From 2008 to 2015, there was a marked decline for OL (71% to 43%, P25 lobectomies were performed annually, the total cost of RL was comparable to VL (P=0.09) and OL (P=0.11). CONCLUSIONS: During the study period, the utilization of RL increased substantially and was associated with improved perioperative outcomes compared with VL and OL. When annual hospital volume was >25 cases, these clinical advantages persisted and there was no significant cost difference between RL, VL, or OL. RL is an effective and cost-comparable approach for lobectomy in patients with lung malignancy.

Investigations into the human 8-oxodGTPase, MutT Homolog 1 (MTH1), have risen sharply since the first-in-class MTH1 inhibitors were reported to be highly tumoricidal. However, MTH1 as a cancer therapeutic target is currently controversial because subsequently developed inhibitors did not exhibit similar cytotoxic effects. Here, we provide the first direct evidence for MTH1-independent 8-oxodGTPase function in human cancer cells and human tumors, using a novel ATP-releasing guanine-oxidized (ARGO) chemical probe. Our studies show that this functionally redundant 8-oxodGTPase activity is not decreased by five different published MTH1-targeting small molecules or by MTH1 depletion. Significantly, while only the two first-in-class inhibitors, TH588 and TH287, reduced cancer cell viability, all five inhibitors evaluated in our studies decreased 8-oxodGTPase activity to a similar extent. Thus, the reported efficacy of the first-in-class MTH1 inhibitors does not arise from their inhibition of MTH1-specific 8-oxodGTPase activity. Comparison of DNA strand breaks, genomic 8-oxoguanine incorporation, or alterations in cellular oxidative state by TH287 versus the noncytotoxic inhibitor, IACS-4759, contradict that the cytotoxicity of the former results solely from increased levels of oxidatively damaged genomic DNA. Thus, our findings indicate that mechanisms unrelated to oxidative stress or DNA damage likely underlie the reported efficacy of the first-in-class inhibitors. Our study suggests that MTH1 functional redundancy, existing to different extents in all cancer lines and human tumors evaluated in our study, is a thus far undefined factor which is likely to be critical in understanding the importance of MTH1 and its clinical targeting in cancer.

Surgical excision of substernal thyroid goiters is usually achieved through a conventional transcervical approach, and transthoracic excision is rarely necessary. Currently, there are no clear guidelines for substernal thyroid goiters that may require a transthoracic approach. This study examined what preoperative factors were significantly associated with transthoracic surgical excision for substernal thyroid goiters.A retrospective review of prospectively collected data of 109 patients with substernal thyroid goiters from a single institution was performed. The patients were stratified by transcervical and transthoracic approaches for substernal thyroid goiters. The factors possibly predictive of a transthoracic approach, including substernal extension beyond the thoracic inlet, patient-reported symptoms, tracheal deviation, and malignancy, were analyzed. Demographics including age, sex, and race, among others, were also studied.Of 1,080 patients who underwent surgical resection for multinodular goiter, there were 109 (10%) patients with substernal thyroid goiters. Of the substernal thyroid goiter group, 11 (10%) patients underwent partial sternotomy, whereas 6 (5.5%) underwent total sternotomy. On logistic regression, only substernal component of the thyroid goiter extending beyond the sternal notch into the mediastinum was statistically significant in predicting sternotomy (odds ratio 3.43, confidence interval 1.65-6.41, Plt; .001). Substernal thyroid goiters with mediastinal extension of ≥5 cm beyond the sternal notch showed a sensitivity of 94% and specificity of 86.5% to predict need of sternotomy.Patients with substernal thyroid goiters who exhibit progressive enlargement and/or compressive symptoms should undergo surgical excision. Although most are removed through the conventional transcervical approach, substernal thyroid goiters with a depth of mediastinal extension ≥5 cm have a high likelihood of requiring sternotomy.

The most common posterior mediastinal masses are neurogenic tumors such as peripheral nerve sheath tumors (PNST). Schwannomas, a subtype of PNST, are most often benign, well encapsulated tumors of neural crest cell origin, and are frequently incidentally found, ranging in size from small asymptomatic mediastinal tumors to large masses. Rarely, large schwannomas are discovered when symptoms develop due to compression or involvement of nearby structures leading to an array of possible sequela which can include, but not limited to, persistent cough, hemoptysis, and dysphagia. Management decisions are based off of tumor size, location, concern for underlying malignant pathology, and potential for complications related to tumor invasion of vital anatomical structures. A majority of the schwannomas undergo surgical resection, though a subset of small, asymptomatic, benign tumors on imaging or pathology may be managed with surveillance. This case report describes a large posterior mediastinal schwannoma adherent to the posterior aortic arch and encasing the left subclavian and vertebral arteries. Surgical resection required vascular resection of a segment of the left subclavian artery and graft reconstruction using polytetrafluoroethylene (PTFE). This report further highlights the importance of preoperative planning with consideration of a multidisciplinary approach in preparation for resection of large, complex posterior mediastinal masses.

Melanoma as a very aggressive type of cancer is still in urgent need of improved treatment. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and arginine deiminase (ADI-PEG20) are two of many suggested drugs for treating melanoma. Both have shown anti-tumor activities without harming normal cells. However, resistance to both drugs has also been noted. Studies on the mechanism of action of and resistance to these drugs provide multiple targets that can be utilized to increase the efficacy and overcome the resistance. As a result, combination strategies have been proposed for these drug candidates with various other agents, and achieved enhanced or synergistic anti-tumor effect. The combination of TRAIL and ADI-PEG20 as one example can greatly enhance the cytotoxicity to melanoma cells including those resistant to the single component of this combination. It is found that combination treatment generally can alter the expression of the components of cell signaling in melanoma cells to favor cell death. In this paper, the signaling of TRAIL and ADI-PEG20-induced arginine deprivation including the main mechanism of resistance to these drugs and exemplary combination strategies is discussed. Finally, factors hampering the clinical application of both drugs, current and future development to overcome these hurdles are briefly discussed.

Physicians throughout the world, across various specialties, are faced with diagnostic challenges of appropriately identifying the source of hemotosysis, which could range from a simple treatable infection, to the more ominous massive hemorrhage from the aorta requiring emergency, life saving surgery. Aortobronchopulmonary fistula, which is an abnormal communication between the thoracic aorta and the pulmonary tree, is an uncommon but often lethal condition if not promptly surgically intervened. Over the decades, the underlying cause has shifted, from primarily due to an aortic infection, such as tuberculosis, to now secondarily as a result of endovascular repair of the intrathoracic aorta. The best treatment modality, whether open surgical repair, endovascular management, or hybrid approach continues to be debated given the high operative morbidity and mortality of open repair and need to address the pulmonary communication, with optimal management still undetermined.

Radiostrontium isotopes (Sr, Sr, and Sr) are major fission by-products in nuclear reactors, in radiological events, and in environmental radioactive contamination. A method to analyze Sr and Sr in water has been developed using gradient elution with dilute hydrochloric acid and cation exchange resin, followed by carbonate precipitation. Counting was done on a gas proportional counter. The sample was recounted a second time after 2 to 3 wk to permit Y, a progeny of Sr, to achieve secular equilibrium and to allow Sr and Sr to be determined. This method was found to be simple, exhibiting high recovery, reduced use of hazardous chemicals, and lower cost compared to other current methods. An extensive comparison of the performance of the cation exchange method vs. a method using strong nitric acid (US Environmental Protection Agency Method 905.0) and a method using a specific strontium resin was conducted on performance test samples containing Sr (in a number of matrices) from the US Department of Energy's Mixed Analyte Performance Evaluation Program and mixed Sr- and Sr-containing water samples from the Environmental Resource Associates quality assurance program. The method described here is shown to yield comparable results to others.

Our Enhanced Recovery After Thoracic Surgery protocol was implemented on February 1, 2018, and firmly established 7 months later. We instituted protocol modifications on January 1, 2020, aiming to further reduce postoperative opioid consumption. We sought to evaluate the influence of such efforts on clinical outcomes and the use of both schedule II and schedule IV opioids following robotic thoracoscopic procedures.A retrospective study of patients undergoing elective robotic procedures between September 1, 2018, and December 31, 2020, was conducted. Essential components of pain management in the original protocol included nonopioid analgesics, intercostal nerve blocks with long-acting liposomal bupivacaine diluted with normal saline, and opioids (ie, scheduled tramadol administration and as-needed schedule II narcotics). Protocol optimization included replacing saline diluent with 0.25% bupivacaine and switching tramadol to as needed, keeping other aspects unchanged. Demographic characteristics, type of robotic procedures, postoperative outcomes, and in-hospital and postdischarge opioids prescribed (ie, milligrams of morphine equivalent [MME]) were extracted from electronic medical records.Three hundred twenty-four patients met the inclusion criteria (159 in the original and 183 in the optimized protocol). There was no difference in postoperative outcomes or acute postoperative pain; there was a significant reduction of in-hospital and postdischarge opioid requirements in the optimized cohort. For anatomic resections: mean, 60.0 MME (range, 0-60.0 MME) versus mean, 105.0 MME (range, 60.0-150.0 MME), and other procedures: mean, 0 MME (range, 0-60 MME) versus mean, 140.0 (range, 60.0-150.0 MME) (Small modifications to our protocol for pain management strategies are safe and associated with significant decrease of opioid requirements, particularly schedule II narcotics, during the postoperative period without influencing acute pain levels.

Objective The use of segmentectomy for peripheral T ≤2 cm, N0 non-small cell lung cancer (NSCLC) has increased in the last decade. We sought to compare clinical outcomes and overall survival between robotic, video-assisted thoracoscopic surgery (VATS), and open segmentectomy. Methods The National Cancer Database was queried for patients with clinical T ≤2 cm, N0 NSCLC who underwent segmentectomy via robotic, thoracoscopic (VATS), and open approaches (2010 to 2015). Univariate and Cox regression analyses were used to compare surgical approaches and to evaluate predictors of overall survival. Statistical analyses were done using SPSS Version 21.0. Results Segmentectomy was performed in 3,888 patients during the study period with 406 robotic, 1,837 VATS, and 1,645 open patients. VATS and robotic segmentectomy were performed more often at academic or comprehensive community cancer programs as compared to community programs ( P < 0.05). Conversion to open thoracotomy was similar between robotic and VATS groups when stratified by hospital volume. Lymph node yield was significantly higher for robotic (median = 6), compared to VATS (median = 5) or open (median = 4; P < 0.001). Length of stay was decreased for robotic versus open ( P < 0.01). No differences in 30-day readmissions ( P = 0.12) were observed among the 3 modalities. Overall survival was similar among groups ( P = 0.18). Conclusions Robotic segmentectomy provides similar clinical outcomes compared to other standardized approaches for clinical T ≤2 cm, N0 NSCLC. A higher lymph node yield in robotic segmentectomy was not associated with improved survival in this study population.

We present a rare case pulmonary metastasis of an early stage endometrial cancer nearly 20 years after curative surgical resection. Our patient had a remote history of hysterectomy for endometrial cancer in 1998 and later had Stage 1B right upper lobe lung cancer treated with lobectomy and adjuvant chemotherapy in 2014. She was found to have an enlarging nodule in the left upper lobe in 2018, which was thought to be another primary lung cancer. She underwent left upper lobe segmentectomy for an intraoperative diagnosis of adenocarcinoma by diagnostic wedge resection of the lung nodule. Final pathologic examination of the resected tumor demonstrated an endometrial adenocarcinoma. It is important for thoracic surgeons to remain vigilant, keeping secondary lung cancer in the differential diagnosis for patients with complex oncologic histories.

Critical airway stenosis presents a challenge for surgeons and anesthesiologists alike in securing a reliable airway for adequate ventilation. The use of veno-venous (VV) extra-corporeal membrane oxygenation (ECMO) has been described as a strategy to provide adequate gas exchange in such instances. We present a case of a young female with a complex paratracheal mass significantly compressing the trachea in whom a planned intra-operative VV ECMO was instituted to allow safe oro-tracheal intubation of a double lumen endotracheal tube for lung isolation and tumor resection.

This program director survey attempts to determine how coronavirus 2019 (COVID-19) pandemic is impacting current training in cardiothoracic surgery. A transition to virtual didactic sessions may prove beneficial with increasing attendance. On the other hand, decreasing live simulation and case volumes may jeopardize achieving competency in surgical skills.

Mediastinal paragangliomas are very uncommon neuroendocrine neoplasms. Due to their tissue of origin (sympathetic ganglia of the great vessels), they tend to arise deep within pericardial space and, more importantly, intimately attached to great vessels, which makes surgical resection, even with cardiopulmonary bypass, very challenging. This commentary accompanies the case report describing complex surgical management of a paraganglioma located in the anterior mediastinum that was initially thought to be a thymoma.

Stereotactic body radiation therapy (SBRT) is increasingly being offered for early stage non-small cell lung cancer (NSCLC). We sought to evaluate long-term survival outcomes after lobectomy and SBRT in patients aged 80 years or more with stage I NSCLC.The National Cancer Database was queried for patients with clinical stage IA and IB (size 40 mm or smaller) NSCLC who underwent SBRT or lobectomy. Only patients with no comorbidities were selected. Number of lymph nodes (LN) examined was used to stratify lobectomy patients into 0 LN, 1 to 6 LN, and 7 or more LN. Propensity score analysis was used to adjust treatment groups. Kaplan-Meier and multivariate Cox regression analysis were used for survival analysis.A total of 8964 patients with stage I NSCLC treated with lobectomy were compared with 286 patients who received SBRT. Using propensity matched pairs, lobectomy (7 LN or more) had significantly improved survival as compared with SBRT (median 74 vs 53.2 months, P.05); however, no survival differences were observed when 0 LN were sampled (median 53.8 vs 52.3 months, P = .88). In multivariate analysis, lobectomy was associated with significantly improved survival (hazard ratio 0.726; 95% confidence interval; 0.580 to 0.910; P = .005). In addition, age, sex, high grade, and tumor size were independent predictors of survival.Among healthy octogenarians with clinical stage I NSCLC who are good surgical candidates, lobectomy offers better survival than SBRT. Adequate LN dissection allows true nodal staging and opportunity for adjuvant treatment when unsuspected nodal metastases are found.

Background: EBUS-TBNA is an integral tool in the diagnosis and staging of lung cancer and other diseases involving mediastinal lymphadenopathy. Most studies attesting to the performance of EBUS-TBNA are prospective analyses performed under strict protocols. The objective of our study was to compare the accuracy of EBUS-TBNA to surgery in diagnosing hilar and mediastinal pathologies in a tertiary hospital, staffed by pulmonologists with and without formal interventional pulmonary training. Methods: We retrospectively analyzed subjects who underwent EBUS-TBNA followed by a confirmatory surgical procedure from January 2012 to December 2018. The primary outcome was to evaluate the accuracy of EBUS-TBNA in the diagnosis of all mediastinal disease. Secondary analyses determined the accuracy of EBUS-TBNA in cancer, NSCLC, and non-malignant lesions individually. Results: One hundred and forty-three subjects had an EBUS-TBNA procedure followed by surgery. EBUS-TBNA for all pathologies had an accuracy of 81.2% (CI 95% 73.8-87.4) and sensitivity of 55.1% (CI 95% 41.5-68.3). The accuracy and sensitivity of individual groups were: cancer (81.7, 48.8%), NSCLC (84, 48.3%), and non-malignancy (78.9, 60%). The NSCLC group had 15 false negatives and 5 (33.3%) of them were due to non-sampling of EBUS accessible nodes. Missed sampling led to a change in the final staging in 8.6% of NSCLC subjects. Conclusion: The accuracy of EBUS-TBNA across all groups was comparable to those reported previously. However, the sensitivity was comparatively lower. This was primarily due to the large number of EBUS-TBNA accessible lymph nodes that were not sampled. This data highlights the need for guidelines outlining the best sampling approach and lymph node selection.

Serous borderline tumors are rare, benign ovarian neoplasms that may recur and undergo malignant transformation to low-grade serous carcinomas (LGSCs). In this report, a 50-year-old female with a remote history of a serous borderline ovarian tumor experienced a recurrence of LGSC, presenting as a large solitary subcutaneous mass anterior to the sternum after a 33-year disease-free interval. The described case highlights the unpredictable nature of this disease and the importance of implementing lifelong surveillance strategies.

Increased metabolic activity of cancer cells due to uncontrolled proliferation, often leads to the accumulation of reactive oxygen species (ROS). High ROS can produce tumor-suppressive oxidative DNA damage either directly in the genome or through oxidation of deoxynucleotides that can then be incorporated into DNA. The human 8-oxoguanine glycosylase 1 (OGG1), a base excision repair (BER) enzyme, protects cells from the former by excising genomic 8-oxodG; MutT Homolog 1 (MTH1), the mammalian 8-oxodGTPase, protects cells from the latter by degrading 8-oxo-dGTP. There has been much interest in increasing oxidative DNA damage in tumors as a therapeutic option. Accordingly, inhibitors are being developed that can target both MTH1 and 8-oxodG glycosylase 1 (OGG1) with the speculation that this co-targeting will significantly increase tumor suppression efficiency. Our lab has shown that MTH1 inhibition leads to DNA strand breaks and tumor-suppressive effects in cancers characterized by high MTH1enzymatic activity. Here we assessed whether co-inhibition of OGG1 would provide benefits in tumor-suppressive effects over MTH1 inhibition alone. We first compared OGG1 and MTH1 expression in paired normal versus tumor tissue from lung adenocarcinoma patients and found that, unlike MTH1, OGG1 tends to remain within normal range in cancerous tissue. Similarly, TCGA lung adenocarcinoma patients show minimal OGG1 elevations and a positive correlation between OGG1 and MTH1 mRNA levels even when both are low. This data suggests that tumors with low OGG1 and MTH1 are robustly represented in the tumor continuum. We then co-depleted OGG1/MTH1 in the A549 lung cancer cell line and found this co-depletion led to lower DNA strand breaks and decreased cell senescence over those caused by MTH1 depletion alone. The shMTH1-transduced cells were less sensitive to SU0268, a potent OGG1 inhibitor compared to shGFP-transduced counterparts. We also treated A549 cells with SU0383, a dual OGG1/MTH1 inhibitor. The dual-inhibitor did not consistently increase cytotoxicity either with duration or dose of treatment beyond single inhibitors or combined single MTH1 and OGG1 inhibitors. In conclusion, our findings suggest that the co-inhibition of OGG1 with MTH1 does not produce enhanced therapeutic benefit in tumor cells, and could instead diminish the tumor-inhibitory effects of MTH1 inhibition that arise from induction of DNA strand breaks and p53-induced senescence. Citation Format: Laura Misiara Lincheta, Ling Zhang, Govindi Samaranayake, Nisha Sharma, Dao Nguyen, Yu-Ki Tahara, Eric Kool, Priyamvada Rai. Low OGG1 protects against the DNA damage induced by MTH1 inhibition [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2076.