Human Adipose Derived Stem Cells Enhance Healing in a Rat Model of Esophageal Injury with Stent.

BACKGROUND: Mesenchymal stem cells have been proven to promote cellular recruitment and remodeling during healing. Considering challenges encountered in the healing process of esophageal injury, we sought to evaluate the effect of human adipose derived stem cells (hASC) on esophageal injury with stent and to assess the feasibility of submucosal hASC injection as a mechanism of delivery. METHODS: An intrabdominal esophagotomy was created in rodents with placement of an expandable fully covered metal esophageal stent. A submucosal injection of 2 × 106 hASC was delivered in experimental animals. Animals were sacrificed on postoperative day 3 (POD3) or 7 (POD7). Macroscopic, immunohistochemical and immunofluorescence analyses were conducted to assess for markers of healing and viability of transplanted cells. RESULTS: hASC were identified within submucosal and muscular layers with proliferation demonstrated in respective areas on anti-Ki67 stained sections. Lower adhesion and abscess scores were observed in hASC specimens without significant statistical difference. Prevalence of submucosal collagen was increased in samples treated with hASC compared to control, with abundant collagen deposition demonstrated within the POD7 group. Granulation tissue at the site of esophageal injury was more prominent in tissue sections treated with hASC compared to control, with significantly higher density at POD3 (control 1.94 versus hASC 2.83, P < 0.01). CONCLUSIONS: Presence of hASC at the site of an esophageal injury may enhance wound healing predominantly through increased granulation and decreased inflammation in conjunction with esophageal stent placement. Targeted submucosal injection at the time of esophageal stent placement is an effective delivery method of hASC therapy.

An Atypical Presentation of Gonococcal Endocarditis.

A 53-year-old male presented following cardiac arrest, followed by cardiopulmonary resuscitation. He was found to have myocardial infarction, bihemispheric cerebral embolization and mitral valve endocarditis. Mitral valve replacement was performed and Neisseria gonorrhoeae was detected on PCR. This case represents a valuable addition to the limited reports on gonococcal endocarditis.

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.

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.

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.

Minimally invasive combined approach robotic thymectomy and transcervical total thyroidectomy.

Myasthenia gravis (MG) is the most common autoimmune disorder affecting the neuromuscular junction in the USA. It is not uncommon for these patients to have concomitant autoimmune diseases including autoimmune thyroid disease. We describe here our method of performing a reproducible robotically assisted one-stage thymectomy and thyroidectomy. An African-American woman presented to our institution with a medical history of hypertension, morbid obesity, type 2 diabetes mellitus, symptomatic MG and symptomatic non-toxic substernal multinodular goitre. A one-stage minimally invasive right-sided robotic radical thymectomy and a transcervical total thyroidectomy with excision of the substernal goitre was successfully performed. The treatment of thyroid and thymus pathologies varies drastically from medical observation to surgery. This combined approach surgery clearly benefits the patient by offering similar operative time, fewer operative and postoperative recovery experiences, decreased anaesthesia risks associated with MG patients through fewer intubations, and a faster return to baseline function.

COVID-19's impact on lung tissue: A case report.

INTRODUCTION: The novel coronavirus has spread globally, however, there continues to be little information regarding management, treatment, and complications encountered by infected patients. Prior to COVID-19, guidelines had been well established for managing empyema, however, evidence is lacking for such patients possessing a COVID-19 infection. In the spirit of collaborative knowledge, we endeavor to present a COVID-19 case from our tertiary care institution. CASE PRESENTATION: A 59-year-old Caucasian male with a past medical history of chronic obstructive pulmonary disease and hypertension was transferred to our hospital for escalation of care of COVID pneumonia. Pharmaceutical treatment included an IL-6 inhibitor (tocilizumab). The patient's hospital course was complicated by superimposed bacterial pneumonia with development of a loculated pleural empyema. On day 57, a left anterolateral muscle-sparing thoracotomy and complete pulmonary decortication was performed. The patient made a successful recovery. CLINICAL DISCUSSION: This patient's vascular dysfunction associated with shunting secondary to pulmonary microthrombi, provides rationale for the liberal use of therapeutic anticoagulation in COVID patients. The superimposed bacterial pneumonia raises concerns over the use of tocilizumab in COVID-19 patients. It is necessary to understand whether current guidelines will need to be amended for the treatment of coagulopathies to avoid pulmonary vascular dysfunction. CONCLUSION: Thoracic surgery can be carried out safely, both for patients and practitioners, during the pandemic. Microvascular occlusions within the pulmonary vasculature contribute to the severe hypoxia and need for anticoagulation in severe COVID-19 cases. Clinical pathways for common clinical presentations, such as empyema, may need to be re-evaluated during this global crisis.

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.

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.

Malignant pleural neoplasm with both differentiation of epithelioid mesothelioma and squamous-cell carcinoma, a rare phenomena.

Malignant mesothelioma, a neoplasm arising within the serosal surfaces, has been linked closely to asbestos exposure. We present a case of 72-year-old male with a 27 year work-related history of asbestos exposure who presented with dyspnea. Chest computed tomography scan showed a large, right pleural effusion with compressive right lung atelectasis. Biopsies, subsequent pleurectomy and lung wedge resections revealed epithelioid malignant mesothelioma with associated focal non-keratinizing squamous-cell carcinoma, supported by extensive immunohistochemical stains and molecular studies. The patient was treated with 6 cycles of carboplatin/pemetrexed, showing no new metastases. Seven months post-treatment, the patient presented with progressive dyspnea and large pleural effusions. Bilateral pleural fluid was collected and showed malignant epithelioid cells, morphologically similar to the patient's pleural neoplastic cells. However, the tumor was positive for squamous cells markers and showed BAP1 loss, while negative for mesothelial markers. The findings support the diagnosis of squamous-cell carcinoma and were consistent with the patient's previously diagnosed pleural neoplastic origin. A malignant mesothelioma associated with squamous-cell carcinoma is a rare phenonmenon. To our knowledge, only two case reports are available in current literature. This unique case shows a single pleura tumor differentiating as both malignant mesothelioma and squamous-cell carcinoma. Squamous-cell carcinoma is the predominating malignancy seen within the bilateral pleural effusions, a potential pitfall for cytology specimen diagnosis.

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.

Trisegmentectomy for traumatic left superior pulmonary vein pseudoaneurysm.

Traumatic pulmonary vein pseudoaneurysms are an extremely rare and dangerous phenomenon. These pseudoaneurysms are caused by both penetrating and blunt thoracic trauma, with late sequelae of pseudoaneurysm rupture and high output cardiac failure secondary to arteriovenous fistula. We present a unique case of pulmonary vein pseudoaneurysm due to penetrating chest trauma managed by segmentectomy using thoracic principles of lung preservation.

Valvular Cytomegalovirus Endocarditis.

Endocarditis is a rare presentation for cytomegalovirus (CMV) infection. We present the case of a 49-year-old man who underwent mitral and tricuspid valve replacement for valvular CMV endocarditis. The patient's past medical history was significant for human immunodeficiency virus, intravenous drug abuse, and chronic hepatitis B. During his clinical course, he was found to have tricuspid and mitral valve vegetations. After progressive valvular destruction despite antibiotic therapy, he underwent successful mitral and tricuspid valve replacement. Pathologic analysis of the culture-negative valve specimens were found to contain inclusion bodies consistent with CMV, and quantitative serum polymerase chain reaction returned a highly elevated CMV DNA count.

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.