Liposomal Bupivacaine Versus Bupivacaine and Dexamethasone Intercostal Nerve Blocks for Robotic Thoracic Surgery: A Randomized Clinical Trial.

Introduction For peripheral nerve blocks, using either the liposomal formulation of bupivacaine or plain bupivacaine with epinephrine and dexamethasone as an adjuvant has been shown to improve postoperative pain scores. In a single-blinded, randomized controlled study of patients undergoing robotic-assisted thoracoscopic surgery, we determined if bupivacaine with epinephrine and dexamethasone was noninferior to liposomal bupivacaine mixed with plain bupivacaine when administered intraoperatively as an intercostal nerve block (INB). Methods A total of 34 patients undergoing robotic-assisted thoracoscopic surgery were randomized to receive one of two injectate mixtures during their intraoperative INB. Group LB was administered 266 mg of 13.3 mg/mL liposomal bupivacaine with 24 mL of 0.5% plain bupivacaine, while Group BD was given 42 mL of 0.5% bupivacaine with epinephrine and 8 mg of dexamethasone. The primary outcomes were mean postoperative numerical pain ratings and mean postoperative opioid analgesic requirements. Secondary outcomes included adjuvant pain medication consumption, hospital length of stay, and total opioid use in oral morphine equivalents. Results Group LB exhibited no significant difference in pain scores (p = 0.437) and opioid analgesic requirement (p = 0.095) within the 72-hour postoperative period when compared to Group BD. The median total postoperative opioid requirement was 90 mg in Group LB, compared to 45 mg in Group BD. There were no significant differences in the use of postoperative adjuvant pain medications (gabapentin, p = 0.833; acetaminophen, p = 0.190; ketorolac, p = 0.699). Hospital length of stay did not differ between the groups. Conclusions INBs with the addition of dexamethasone as an adjuvant to 0.5% bupivacaine with epinephrine provided noninferior postoperative analgesia compared to liposomal bupivacaine mixed with plain 0.5% bupivacaine.

A real-world study evaluating the safety and utility of a two-row stapler reload on pulmonary vasculature.

Background: Endoscopic staplers are common surgical devices used for the ligation and division of vasculature in thoracic procedures. When a stapler ligates and divides pulmonary vasculature, potentially catastrophic intraoperative bleeding at the staple-line may occur. The aim of this study was to confirm the safety and discuss the utility of a two-row stapler reload, by assessing the incidence of clinically necessary intraoperative hemostatic intervention when applied to pulmonary vasculature in real-world applications. Methods: This study was designed as a prospective non-comparative registry study conducted in seven centers across the United States, to confirm the safety and performance of Signia™ Small Diameter Reloads (SDR) when used for indicated thoracic surgical procedures. The primary endpoint was the incidence of hemostatic intervention related to the ligation and division of pulmonary arteries and veins. A five-point Likert scale scored hemostasis of each SDR staple-line. Secondary endpoints included the incidence of device-related only adverse events (AEs), device deficiencies, and procedure-related hospital readmission up to and including 30 days post operation. Results: SDR was fired 302 times across pulmonary vasculature in 120 subjects. Three firings required clinically necessary hemostatic intervention for an intervention rate of 0.99% (3 of 302 firings). Moreover, 97.5% (117 of 120 subjects) had intact SDR staple-lines regardless of surgical access or stapler handle preference. Only 4 (3.3%) thoracoscopic and robotic procedures converted to open, but none were due to SDR staple-lines. There was no statistically significant difference between the Likert score of transected arteries compared to veins (P=0.61). There were no device deficiencies or device-only related AEs reported. Conclusions: In this study, the two-row stapler reloads demonstrated favorable safety and efficacy profiles when fired across hilar vessels in the thoracic space with a 99% hemostatic rate, independent of surgical access and stapler handle preference.

Diagnostic Workup and Therapeutic Intervention of Hiatal Hernias Discovered as Incidental Findings on Computed Tomography.

BACKGROUND: Computed tomography imaging routinely detects incidental findings; most research focuses on malignant findings. However, benign diseases such as hiatal hernia also require identification and follow-up. Natural language algorithms can help identify these non-malignant findings. METHODS: Imaging of adult trauma patients from 2010 to 2020 who underwent CT chest/abdomen/pelvis was evaluated using an open-source natural language processor to query for hiatal hernias. Patients who underwent subsequent imaging, endoscopy, fluoroscopy, or operation were retrospectively reviewed. RESULTS: 1087(10.6%) of 10 299 patients had incidental hiatal hernias: 812 small (74.7%) and 275 moderate/large (25.3%). 224 (20.7%) had subsequent imaging or endoscopic evaluation. Compared to those with small hernias, patients with moderate/large hernias were older (66.3 ± 19.4 vs 79.6 ± 12.6 years, P < .001) and predominantly female (403[49.6%] vs 199[72.4%], P < .001). Moderate/large hernias were not more likely to grow (small vs moderate/large: 13[7.6%] vs 8[15.1%], P = .102). Patients with moderate/large hernias were more likely to have an intervention or referral (small vs moderate/large: 6[3.5%] vs 7[13.2%], P = .008). No patients underwent elective or emergent hernia repair. Three patients had surgical referral; however, only one was seen by a surgeon. One patient death was associated with a large hiatal hernia. CONCLUSIONS: We demonstrate a novel utilization of natural language processing to identify patients with incidental hiatal hernia in a large population, and found a 10.6% incidence with only 1.2%. (13/1087) of these receiving a referral for follow-up. While most incidental hiatal hernias are small, moderate/large and symptomatic hernias have high risk of loss-to-follow-up and need referral pipelines to improve patient outcomes.

Exploring cell competition for the prevention and therapy of esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma (ESCC) is characterized by the development of cancer in the esophageal squamous epithelium through a step-by-step accumulation of genetic, epigenetic, and histopathological alterations. Recent studies have demonstrated that cancer-associated gene mutations exist in histologically normal or precancerous clones of the human esophageal epithelium. However, only a small proportion of such mutant clones will develop ESCC, and most ESCC patients develop only one cancer. This suggests that most of these mutant clones are kept in a histologically normal state by neighboring cells with higher competitive fitness. When some of the mutant cells evade cell competition, they become "super-competitors" and develop into clinical cancer. It is known that human ESCC is composed of a heterogeneous population of cancer cells that interact with and influence their environment and neighbors. During cancer therapy, these cancer cells not only respond to therapeutic agents but also compete with each other. Therefore, competition between ESCC cells within the same ESCC tumor is a constantly dynamic process. However, it remains challenging to fine-tune the competitive fitness of various clones for therapeutic benefits. In this review, we will explore the role of cell competition in carcinogenesis, cancer prevention, and therapy, using NRF2, NOTCH pathway, and TP53 as examples. We believe that cell competition is a research area with promising targets for clinical translation. Manipulating cell competition may help improve the prevention and therapy of ESCC.

Utilization Large Animal Research as an Adjunct for Surgical Education Increases Perceived Resident Confidence.

Surgical education has evolved over time to incorporate supplemental modalities of training beyond the operating room. Even with the utility of simulation software and didactic education, there is still a need to provide surgical residents with experience in live tissue dissection and tissue handling while maintaining patient safety. In our program, after two clinical years, residents participate in a year of translational research which uses porcine models for complex open abdominal procedures. During the porcine surgeries, our residents are guided by the supervising attending to perform key portions of the procedure typically reserved for those more senior trainees. We found in a survey that research residents after two clinical years found this experience with large animal surgeries helped them better navigate anatomic structures and would recommend this to future trainees. We believe this dual-purpose research-training model provides a valuable resource that can be adapted to other programs.

The Early Impact of the COVID-19 Pandemic on Lung, Colorectal, and Breast Cancer Screening and Treatment at a Tertiary Cancer Center.

OBJECTIVES: During the coronavirus-19 pandemic, experts recommended delaying routine cancer screening and modifying treatment strategies. We sought to understand the sequalae of these recommendations. MATERIALS AND METHODS: We performed a retrospective single-center analysis of screening, diagnosis, and treatment of lung, colorectal, and breast cancer. Data was collected from our institutional cancer registry. Prepandemic (2016-2019) was compared with pandemic (2020) data. RESULTS: Three thousand three sixty one screening chest computed tomography scans (CTs), 35,917 colonoscopies, and 48,093 screening mammograms were performed. There was no difference in CTs [81.0 (SEM10.0) vs. 65.6 (SEM3.29), P =0.067] or mammograms [1017.0 (SEM171.8) vs. 809.4 (SEM56.41), P =0.177] in 2020 versus prepandemic. There were fewer colonoscopies in 2020 [651.4 (SEM103.5) vs. 758.91 (SEM11.79), P =0.043]. There was a decrease in cancer diagnoses per month in 2020 of lung [22.70 (SEM1.469) vs. 28.75 (SEM0.8216), P =0.003] and breast [38.56 (SEM6.133) vs. 51.82 (SEM1.257), P =0.001], but not colorectal [13.11 (SEM1.467) vs. 15.88 (SEM0.585), P =0.074] cancer. There was no change in stage at presentation for lung ( P =0.717), breast ( P =0.115), or colorectal cancer ( P =0.180). Lung had a shorter time-to-treatment in 2020 [38.92 days (SEM 2.48) vs. 66 (SEM1.46), P =0.002]. CONCLUSIONS: In 2020, there was no difference in screening studies for lung and breast cancer but there was a decrease in new diagnoses. Although there were fewer colonoscopies performed in 2020, there was no change in new colorectal cancer diagnoses. Despite changes in guidelines during the pandemic, the time-to-treatment for lung cancer was shorter and was unchanged for colorectal and breast cancer. These findings highlight the importance of continuing care for a vulnerable patient population despite a pandemic.

The State of Racial and Gender Diversity in Cardiothoracic Surgery Training.

BACKGROUND: The field of cardiothoracic surgery has been striving to increase its gender and racial diversity. We sought to examine changes in gender and racial diversity in cardiothoracic fellowships and integrated residencies in the past decade. METHODS: Accreditation Council for Graduate Medical Education data were obtained from 2011 to 2019. Linear trends were assessed for year-by-year data. Average percentages of women and underrepresented minorities were then calculated in 3-year intervals. Intervals were compared with Student's t test and χ2 tests. RESULTS: There was no statistically significant increase in percent female trainees in cardiothoracic fellowships (18.5% to 22.1%, P = .10) or integrated residencies (22.8% to 27.8%, P = .17), despite a significant increase in percent female applicants to fellowship (18.2% to 35.3%, P < .01) and integrated residency (8.9% to 33.0%, P < .01). Cardiothoracic fellowships had no increase in underrepresented minority trainees (8.3% to 9.4%, P = .48). Underrepresented minority trainees in integrated residencies increased from 2.7% to 6.9% (P = .03). Although there was no significant increase in underrepresented minority applicants to fellowships (10.2% to 11.3%, P = .66), the percent of underrepresented minority applicants to integrated residencies increased from 13.1% to 19.3% (P < .01). CONCLUSIONS: Cardiothoracic surgery training programs are attracting more female applicants, but that has not yet resulted in a higher percentage of female trainees. Although percentages of underrepresented minorities increased among integrated residency applicants and trainees, they remain low compared with other specialties. These data reflect positive changes but also highlight that much remains to be done to increase diversity in cardiothoracic surgery training.

Liposomal Bupivacaine Versus Bupivacaine for Intercostal Nerve Blocks in Thoracic Surgery: A Retrospective Analysis.

BACKGROUND: Liposomal bupivacaine (LipoB), delivered via intercostal nerve blocks (ICNBs), is increasingly being used for postoperative pain control in thoracic surgery patients, but there is limited data on its effectiveness when compared to standard bupivacaine. OBJECTIVE: We sought to compare postoperative opioid use, pain control, and length of stay (LOS) in patients undergoing thoracic surgery with LipoB ICNBs vs patients undergoing thoracic surgery with ICNBs using standard bupivacaine. STUDY DESIGN: A retrospective analysis. SETTING: Research took place in a tertiary academic medical center. METHODS: A transition in the standard of care from standard bupivacaine to LipoB for ICNBs in March of 2014 allowed us to compare 2 cohorts: patients who received bupivacaine ICNBs from January 2013 through February of 2014 and patients who received LipoB ICNBs from March 2015 through November 2017. We included patients who underwent thoracic surgery for lung cancer using robotic-assisted thoracic surgery (RATS), video-assisted thoracic surgery (VATS), or traditional open thoracotomy, and documentation of ICNB in the operative note. We collected data on pain scores (Visual Analog Scale [VAS]) and opioid consumption (converted to oral morphine equivalents [OMEs]) intraoperatively, on postoperative day (POD) 0, POD 1, POD 2, and POD 3. We also analyzed data on length of stay [LOS]. A primary analysis was performed on the effects of LipoB vs bupivacaine across all surgery types on opioid consumption, pain scores, and LOS with a secondary analysis on the same endpoints per individual surgery type. RESULTS: A total of 129 patients were included from the predefined study periods (n = 62 LipoB and n = 67 standard bupivacaine). Across all surgery types, LipoB decreased opioid utilization vs standard bupivacaine (P < .01). Post-hoc testing revealed that this difference existed intraoperatively (55 ± 5 vs 69 ± 4 mg OME, P = .03) and on POD 0 (44 ± 6 vs 68 ± 6 mg OME, P < .01). Surgical subtype analysis revealed that this difference was mostly driven by lower opioid consumption in patients undergoing RATS. When compared across all surgery types, LipoB vs bupivacaine did not affect postoperative pain scores. However, subgroup analysis showed that pain scores were lower in the LipoB vs standard bupivacaine group undergoing VATS on POD 0, 1, and 2. The LOS across all thoracic surgery types was lower in the LipoB group when compared to the standard bupivacaine group (median, 4 days [IQR 2.0-6.0] vs median, 5 days [IQR 3.0-8.0], P < .01). Subgroup analysis showed that the LOS in patients undergoing VATS with LipoB ICNBs was shorter compared to patients receiving bupivacaine ICNBs. LIMITATIONS: The retrospective nature of this study makes it prone to several types of bias. CONCLUSION: ICNBs with LipoB for thoracic surgery leads to lower opioid consumption and shorter LOS when compared to ICNBs with standard bupivacaine. The benefit of LipoB over standard bupivacaine for ICNBs appears especially relevant in VATS or RATS procedures. KEY WORDS: Intercostal nerve block, liposomal bupivacaine, RATS, regional anesthesia, robotic-assisted thoracoscopic surgery, thoracotomy, VATS, video-assisted thoracoscopic surgery.

Status of sentinel lymph node mapping in non-small cell lung cancer.

Sentinel lymph node mapping has become the standard of care in melanoma and breast cancer, contributing to marked improvements in accurate staging and targeted treatment, while decreasing morbidity of aggressive nodal bed dissections. Since 1999, several groups have proposed similar mapping in lung cancer models with mixed success. This article reviews the research up to date and discusses opportunities to improve accuracy of sentinel lymph node biopsy in non-small cell lung cancer.

Value of circulating insulin-like growth factor-associated proteins for the detection of stage I non-small cell lung cancer.

OBJECTIVE: Circulating biomarkers related to insulin-like growth factor (IGF) signaling are associated with disease progression in multiple carcinomas, but their potential diagnostic value for lung cancer screening has been inadequately examined. We evaluated 9 circulating IGF-related factors for their ability to assign clinical significance to indeterminate pulmonary nodules identified via computed tomography-based radiologic studies. METHODS: Patients (n = 224 stage I non-small cell lung cancer; n = 123 benign) were enrolled by Rush University and the Mayo Clinic and had pretreatment serum evaluated for levels of IGF-1, IGF-2, and insulin-like growth factor binding proteins (IGFBPs) 1-7. The Mann-Whitney rank-sum test and receiver-operator characteristics curves were used to assess differences in biomarker concentrations relevant to malignant versus benign pathology. These targets were used to help refine our companion blood test for assigning clinical significance to computed tomography-detected solitary nodules (discovery cohort, n = 94) and were validated against an independent cohort from the Mayo Clinic (n = 81). RESULTS: Patients with benign pulmonary nodules were found to have serum concentrations of IGFBP-3, IGFBP-5, IGF-1, and IGF-2 that were higher (P = .001, P < .001, P = .002, and P = .011, respectively) than those with non-small cell lung cancer, with distinct associations with histologic subtypes observed. Refinement of our multianalyte classification algorithm using IGF-related factors provided a new panel consisting of interleukin-6, interleukin-1 receptor antagonist, interleukin-10, stromal cell-derived factor-1(α + ß), IGFBP-4, IGFBP-5, and IGF-2 with improved assay performance-achieving a (validated) negative predictive value of 100%. CONCLUSIONS: Our findings suggest a divergent role for IGF signaling in the biology of benign and malignant pulmonary nodules. Upon further validation, these observations may help identify cases of false positives resulting from computed tomography-based screening studies.

Multimodality treatment of pleural mesothelioma.

Although the treatment of malignant pleural mesothelioma has been refined during the past two decades, overall survival from this rather uncommon disease is still extremely poor. Here we review the current multimodal diagnostic and treatment options for patients with mesothelioma and discuss promising new experimental concepts in this disease.

Development of a serum biomarker panel predicting recurrence in stage I non-small cell lung cancer patients.

OBJECTIVE: Molecular diagnostics capable of prognosticating disease recurrence in stage I non-small cell lung cancer (NSCLC) patients have implications for improving survival. The objective of the present study was to develop a multianalyte serum algorithm predictive of disease recurrence in stage I NSCLC patients. METHODS: The Luminex immunobead platform was used to evaluate 43 biomarkers against 79 patients with resectable NSCLC, with the following cohorts represented: stage I (T(1)-T(2)N(0)M(0)) NSCLC without recurrence (n = 37), stage I (T(1)-T(2)N(0)M(0)) NSCLC with recurrence (n = 15), and node-positive (T(1)-T(2)N(1)-N(2)M(0)) NSCLC (n = 27). Peripheral blood was collected before surgery, with all patients undergoing anatomic resection. Univariate statistical methods (receiver operating characteristics curves and log-rank test) were used to evaluate each biomarker with respect to recurrence and outcome. Multivariate statistical methods were used to develop a prognostic classification panel for disease recurrence. RESULTS: No relationship was found between recurrence and age, gender, smoking history, or histologic type. Analysis for all stage I patients revealed 28 biomarkers significant for recurrence. Of these, the log-rank test identified 10 biomarkers that were strongly (P < .01) prognostic for recurrence. The Random Forest algorithm created a 6-analyte panel for preoperative classification that accurately predicted recurrence in 77% of stage I patients tested, with a sensitivity of 74% and specificity of 79%. CONCLUSIONS: We report the development of a serum biomarker algorithm capable of preoperatively predicting disease recurrence in stage I NSCLC patients. Refinement of this panel might stratify patients for adjuvant therapy or aggressive recurrence monitoring to improve survival.

Targeting the insulin-like growth factor receptor pathway in lung cancer: problems and pitfalls.

The insulin-like growth factor (IGF) pathway is a complex pathway involving interactions between membrane-bound receptors, ligands, binding proteins, downstream effectors, and other receptor tyrosine kinase signaling cascades. The IGF pathway has been identified as a potential therapeutic target in non-small cell lung cancer (NSCLC) based on the following provocative factors. Preclinical observations in NSCLC have shown that this pathway is involved in tumor cell proliferation, survival, and invasiveness. In addition, IGF-1R protein expression is found in a significant number of non-small cell tumor specimens. Initial therapeutic efforts involved the development of monoclonal antibodies and tyrosine kinase inhibitors that target IGF-1R, a transmembrane receptor tyrosine kinase. Enthusiasm for targeting this pathway increased when a randomized phase II study showed that combining an anti-IGF-1R monoclonal antibody (figitumumab) with a platinum doublet resulted in a higher response rate and trends for superior progression-free survival and overall survival. Subsequently, a phase III study failed to confirm the promising results observed in the phase II trial. Currently, investigators are studying different monoclonal antibodies and tyrosine kinases targeting IGF-1R. In unselected patients, results presented thus far do not suggest efficacy of this agent. However, retrospective subgroup analyses suggest that circulating IGF-1 levels might identify patients who could benefit from treatment with an IGF-1R monoclonal antibody and may warrant further exploratory studies for predictive molecular markers. The purpose of this paper is to briefly discuss the IGF pathway and its relationship with other signaling pathways in lung cancer and to review the ongoing IGF clinical trials and efforts to identify predictive molecular markers.

Anterior mediastinal mass secondary to histoplasmosis.

Histoplasmosis in the mediastinum is an uncommon diagnosis that presents similarly to other benign and neoplastic conditions encountered in the chest. Here we describe a 36-year-old woman who presented with dyspnea secondary to a large anterior mediastinal mass that was biopsy and culture negative for neoplasm or infection. Video-assisted thoracoscopic surgery biopsy confirmed a large anterior mediastinal mass adherent to the aorta, which contained foci of histoplasmosis species. She is currently undergoing a long postoperative course of itraconozole and an empiric course of oral steroids to prevent development of fibrosing mediastinitis.

Adenocarcinoma in a 40-year-old colonic interposition treated with Ivor Lewis esophagectomy and esophagogastric anastomosis.

Colon interposition for benign stricture is associated with significant perioperative complications that carry high morbidity and mortality, but long-term sequelae such as further strictures and colonic redundancy are often well-tolerated. These benign complications are frequently described in literature, but adenocarcinoma in the colonic graft is a rare complication. We describe a 60-year-old man with a history of benign esophageal stricture who was treated with colon interposition 40 years ago and presented with dysphagia secondary to stage 1 colon graft adenocarcinoma. He was successfully treated with an Ivor Lewis esophagectomy and primary esophagogastric anastomosis.