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INTRODUCTION: A history of lung transplantation is a risk factor for poor outcomes in patients undergoing laparoscopic fundoplication. We wanted to determine whether enhanced recovery after a robotic-assisted surgery program would mitigate these risks. METHODS: We performed a single-center retrospective analysis of the Society of Thoracic Surgery database for patients who underwent elective antireflux procedures from 1/2018 to 2/2021 under the enhanced recovery after surgery program using robotic assistance. We identified the patient and surgical characteristics, morbidity, length of stay, and 30-day readmission rates. RESULTS: Among 386 patients who underwent barrier creation, 41 had previously undergone a lung transplant, either bilateral (n = 28) or single (n = 13). There were no significant differences in postoperative complications (9.8% vs. 5.2%, p = 0.27), median hospital length of stay (1 d vs. 1 d, p = 0.28), or 30-day readmission (7.3% vs. 4.9%, p = 0.46). Bivariate analysis showed that older age (p = 0.03), history of DVT/PE (p < 0.001), history of cerebrovascular events (p = 0.03), opioid dependence (p = 0.02), neurocognitive dysfunction (p < 0.001), and dependent functional status (p = 0.02) were associated with postoperative complications. However, lung transplantation was not associated with an increased risk of postoperative complications (p = 0.28). DISCUSSION: The risk of surgical complications in patients with a history of lung transplantation may be mitigated by the combination of ERAS and minimally invasive surgery such as robot-assisted surgery.
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Recuperación Mejorada Después de la Cirugía , Laparoscopía , Trasplante de Pulmón , Procedimientos Quirúrgicos Robotizados , Humanos , Fundoplicación/métodos , Procedimientos Quirúrgicos Robotizados/efectos adversos , Procedimientos Quirúrgicos Robotizados/métodos , Estudios Retrospectivos , Trasplante de Pulmón/efectos adversos , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/prevención & control , Laparoscopía/efectos adversos , Laparoscopía/métodos , Tiempo de InternaciónRESUMEN
Aberrant expression of the oncogenic retrotransposon LINE-1 is a hallmark of various cancer types, including non-small cell lung cancers (NSCLCs). Here, we present proof-of-principle evidence that LINE-1 analytes in extracellular vesicles (EVs) serve as tools for molecular diagnostics of NSCLC, with LINE-1 status in tumor cells and tissues mirroring the LINE-1 mRNA and ORF1p cargos of EVs from lung cancer cell culture conditioned media or human plasma. The levels of LINE-1 analytes in plasma EVs from ostensibly healthy individuals were higher in females than males. While the profiles of LINE-1 mRNA and ORF1p in African Americans compared to Hispanics were not significantly different, African Americans showed slightly higher ORF1p content, and 2-3 times greater ranges of LINE-1 values compared to Hispanics. Whole plasma ORF1p levels correlated with EV ORF1p levels, indicating that most of the circulating LINE-1 protein is contained within EVs. EV LINE-1 mRNA levels were elevated in patients with advanced cancer stages and in select patients with squamous cell carcinoma and metastatic tumors compared to adenocarcinomas. The observed EV LINE-1 mRNA profiles paralleled the patterns of ORF1p expression in NSCLC tissue sections suggesting that LINE-1 analytes in plasma EVs may serve to monitor the activity of LINE-1 retroelements in lung cancer.
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Carcinoma de Pulmón de Células no Pequeñas , Vesículas Extracelulares , Neoplasias Pulmonares , Femenino , Masculino , Humanos , Carcinoma de Pulmón de Células no Pequeñas/diagnóstico , Carcinoma de Pulmón de Células no Pequeñas/genética , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , Patología Molecular , Retroelementos , Vesículas Extracelulares/genética , ARN Mensajero/genéticaRESUMEN
INTRODUCTION: Preoperative coagulation screening for patients without bleeding disorders remains controversial. The combinatorial risk of INR, aPTT, and platelet count (PLT) abnormalities leading to bleeding requiring transfusion is not known in these patients. We examined the association between abnormal coagulation profile and the risk of transfusion following common elective surgery in patients without bleeding disorders. STUDY DESIGN AND METHODS: We utilized the National Surgical Quality Improvement Program (NSQIP) database from 2004 to 2018 to identify patients without a history of bleeding disorders undergoing common 23 major elective procedures across 10 specialties. Multivariable logistic regression was used to assess the association between coagulation profile and bleeding requiring packed red blood cell transfusion intra-/post-operatively. RESULTS: Of the 672,075 patients meeting inclusion criteria, 53.7% presented with normal coagulation profile preoperatively. Overall, 12.2% (n = 82,368) received transfusion. In the setting of normal aPTT/PLT, both Equivocal INR of 1.1-1.5 (aOR 1.41, 95% CI 1.38-1.44) and Abnormal INR of >1.5 (aOR 1.81, 95% CI 1.71-1.93) were significantly associated with an increased risk of transfusion. Equivocal (60-70) and Abnormal (>70) aPTT with normal INR/PLT did not demonstrate a comparable risk of transfusion. We observed a synergistic effect of combinatorial lab abnormalities on the risk of transfusion when both Abnormal INR/aPTT and Low PLT of <100,000 were present (aOR 5.18, 95% CI 3.04-8.84), compared to the effect of Abnormal INR/aPTT and normal/elevated PLT (aOR 1.90, 95% CI 1.48-2.45). DISCUSSION: The preoperative presence of abnormal findings in INR or PLT was significantly associated with the risk of bleeding requiring transfusion during intraoperative and postoperative periods.
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Trastornos de la Coagulación Sanguínea , Mejoramiento de la Calidad , Humanos , Trastornos de la Coagulación Sanguínea/terapia , Trastornos de la Coagulación Sanguínea/complicaciones , Transfusión Sanguínea , Tiempo de Tromboplastina Parcial , Hemorragia/etiología , Complicaciones Posoperatorias/etiología , Estudios RetrospectivosRESUMEN
BACKGROUND: The optimal extent of resection for a patient with a typical carcinoid tumor has been controversial. Studies suggest that wedge resection is an adequate oncologic operation for this tumor type. MATERIALS AND METHODS: We analyzed the National Cancer Database to determine an optimal surgical resection for patients with a typical carcinoid tumor. We determined the number of patients who had typical carcinoid tumors. We then performed a survival analysis of the propensity-matched group of patients having a pathologic stage I typical carcinoid tumor who had undergone anatomic pulmonary resection (lobectomy and segmentectomy) or wedge resection. RESULTS: A total of 10,265 patients met the inclusion and exclusion criteria: 8956 (87%) had a typical carcinoid tumor, while 1309 patients (13%) had an atypical carcinoid tumor. Among patients with typical carcinoid tumors, there were 7163 patients (80%) who underwent anatomic pulmonary resection (6755 patients with lobectomy, 94% and 408 patients with segmentectomy, 6%) and 1793 patients (20%) who underwent wedge resection. In this cohort, patients who had an anatomic resection had significantly improved 5-y survival compared to patients who had wedge resection (91% versus 84%, P < 0.001). In the propensity score-matched group of stage I typical carcinoid tumors (n = 1348), the patients who had an anatomic resection had significantly improved survival compared to patients who had wedge resections (89% versus 85%, P = 0.01) at 5 y. CONCLUSIONS: The anatomic resection compared to wedge resection was associated with improved survival in patients with early-stage typical carcinoid lung cancer. Surgically fit patients should be considered for anatomic resection for typical carcinoid tumors.
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Tumor Carcinoide , Carcinoma Neuroendocrino , Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Carcinoma Neuroendocrino/patología , Carcinoma de Pulmón de Células no Pequeñas/cirugía , Humanos , Estadificación de Neoplasias , Neumonectomía , Estudios RetrospectivosRESUMEN
BACKGROUND: Manometry is the gold standard diagnostic test for achalasia. However, there are incidences where manometry cannot be obtained preoperatively, or the results of manometry is inconsistent with the patient's symptomatology. We aim to determine if intraoperative use of EndoFLIP can provide a diagnosis of achalasia and provide objective information during Heller myotomy and Dor fundoplication. METHODS: To determine the intraoperative diagnostic EndoFLIP values for patients with achalasia, we determined the optimal cut-off points of the distensibility index (DI) between patients with a diagnosis of achalasia and patients with a diagnosis of hiatal hernia. To evaluate the usefulness of EndoFLIP values during Heller myotomy and Dor fundoplication, we obtained a cohort of patients with EndoFLIP values obtained after Heller myotomy and after Dor fundoplication as well as Eckardt score before and after surgery. RESULTS: Our analysis of 169 patients (133 hiatal hernia and 36 achalasia) showed that patients with DI < 0.8 have a >99% probability of having achalasia, while DI > 2.3 have a >99% probability of having hiatal hernia. Patients with a DI 0.8-1.3 have a 95% probability of having achalasia, and patients with a DI of 1.4-2.2 have a 94% probability of having a hiatal hernia. There were 40 patients in the cohort to determine objective data during Heller myotomy and Dor fundoplication. The DI increased from a median of 0.7 to 3.2 after myotomy and decreased to 2.2 after Dor fundoplication (p < 0.001). The median Eckardt score went down from a median of 4.5 to 0 (p < 0.001). CONCLUSIONS: Our study shows that intraoperative use of EndoFLIP can facilitate the diagnosis of achalasia and is used as an adjunct to diagnose achalasia when symptoms are inconsistent. The routine use of EndoFLIP during Heller myotomy and Dor fundoplication provides objective data during the operation in a group of patients with excellent short-term outcomes.
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Acalasia del Esófago , Miotomía de Heller , Hernia Hiatal , Laparoscopía , Acalasia del Esófago/diagnóstico , Acalasia del Esófago/cirugía , Fundoplicación/métodos , Hernia Hiatal/diagnóstico , Hernia Hiatal/cirugía , Humanos , Laparoscopía/métodos , Resultado del TratamientoRESUMEN
BACKGROUND: Endoluminal functional lumen imaging probe (EndoFLIP) provides an objective measure of the distensibility index (DI) during different parts of hiatal hernia repair. However, the absolute DI measure above a cut-off after creating a barrier alone has not shown a relationship to dysphagia after surgery. We wanted to determine if the change in DI with volume change is associated with dysphagia. METHODS: We included patients who had hiatal hernia repair with EndoFLIP values, including two values taken at the end of the surgical case with different volumes of fluid in the balloon (30 mL and 40 mL). We compared the absolute and change in DI during hiatal hernia repair and performed an analysis to determine if there was a correlation with short-term clinical outcomes. RESULTS: A total of 103 patients met the inclusion and exclusion criteria. Most of the patients underwent Toupet fundoplication (n = 56, 54%), followed by magnetic sphincter augmentation (LINX, n = 28, 27%) and Nissen fundoplication (n = 19, 18%). There was a significant reduction in the DI from the initial DI taken after mobilization of the hiatus (3 mm2/mmHg) and after the creation of the barrier (1.4 mm2/mmHg, p < 0.001). A minority of patients had a decrease or no change in the DI with an increase in balloon volume increased from 30 to 40 mL (n = 37, 36%). Overall, after 1 month, there was a significant decrease in the GERD-HRQL score from 23 to 4 (p < 0.001) and bloat score from 3 to 2 (p = 0.003) with a non-significant decrease in the dysphagia score from 1 to 0 (p = 0.11). Patients who had a decreased or unchanged DI with an increase in the balloon volume from 30 to 40 mL had a significant decrease in their dysphagia score by 2 points (p = 0.04). CONCLUSION: The decreased or unchanged DI with an increase in the balloon volume on EndoFLIP is associated with a significant reduction in dysphagia after surgery. The decrease in DI denotes the esophagus's ability to create higher pressure relative to the change in the cross-sectional area with a larger bolus across the gastroesophageal junction. This measure may be a new marker that can predict short-term outcomes in patients undergoing hiatal hernia repair.
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Trastornos de Deglución , Hernia Hiatal , Laparoscopía , Trastornos de Deglución/etiología , Trastornos de Deglución/cirugía , Unión Esofagogástrica/cirugía , Fundoplicación/métodos , Hernia Hiatal/complicaciones , Hernia Hiatal/cirugía , Herniorrafia , Humanos , Resultado del TratamientoRESUMEN
BACKGROUND: Endoluminal functional lumen imaging probe (EndoFLIP) technology is a tool that can be used to provide intraoperative objective real-time feedback during hiatal hernia repair. We wanted to determine the implication of initial distensibility index (DI) after mobilization of hiatus and final DI after creation of barrier in short-term clinical outcomes. METHODS: We performed a retrospective analysis of prospectively collected data on the intraoperative use of EndoFLIP during hiatal hernia repair at a single institution from 2017 to 2019. We analyzed the initial DI and final DI with the short-term clinical outcomes. RESULTS: There were 163 patients who had Nissen (n = 16), Toupet (n = 79) or magnetic sphincter augmentation (n = 68) with (n = 158) or without (n = 5) hiatal hernia repair with median initial DI was 3.2 mm2/mmHg. We used 3 mm2/mmHg as the cutoff for low (n = 84) vs. high (n = 79) initial DI group. There was no difference in DeMeester score (p = 0.76), the peristalsis on manometry (p = 0.13), type of hiatal hernia (p = 0.98), and GERD-HRQL score prior to surgery (p = 0.73) between the groups. There was significantly higher final DI in the high initial DI group compared to low initial DI group; however, there was no significant difference in the GERD-HRQL score at 1-3 months (p = 0.28). All of the patients had a final DI > 0.5 mm2/mmHg at the end of the case with median final DI of 1.6 mm2/mmHg. None of these patients required steroids (0%) and only one patient (0.6%) required EGD and dilatation as well as re-operation for dysphagia within 3 months. CONCLUSIONS: The initial DI was associated with final DI, but it did not correlate with improvement in short-term GERD-HRQL score. Final DI maintained above the cutoff value led to most of the patients not to require intervention for dysphagia. Use of the EndoFLIP can provide objective data during the operation and prevent severe dysphagia after repair.
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Reflujo Gastroesofágico , Hernia Hiatal , Laparoscopía , Fundoplicación , Reflujo Gastroesofágico/cirugía , Hernia Hiatal/cirugía , Herniorrafia , Humanos , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
BACKGROUND: We postulated that the use of robotics may improve outcomes in hiatal hernia repair. METHODS: We performed a retrospective analysis of a prospectively collected Society of Thoracic Surgery database at a single institution of patients who underwent elective hiatal hernia repair from 2012 to 2017 using either laparoscopy or the da Vinci Xi robot. We compared patient characteristics and outcomes and then performed univariate and multivariate logistic regression modeling to determine the factors associated with postoperative morbidity. RESULTS: There were 293 consecutive patients who underwent elective hiatal hernia repair using either a laparoscopic (n = 151) or a robotic (n = 142) technique. There were no significant differences in age, gender, BMI, smoking history, presence of comorbidity, or hiatal hernia type. Seventy percent of the cases were a repair of either type III or type IV hiatal hernia. There were significantly higher ASA III and IV (7.9% vs. 4.2%, P = 0.03), higher Toupet fundoplication (83.4% vs. 44.4%, P < 0.001), and lower redo-repair (7.3% vs. 20.4%, P = 0.001) in the laparoscopic group compared to the robotic group. The hospital length of stay was significantly shorter (1.3 ± 1.8 vs. 1.8 ± 1.5 days, P = 0.003) and there were significantly lower rates of complications (6.3 vs. 19.2%, P = 0.001) after robotic compared to laparoscopic hiatal hernia repair. There was no difference in readmission rate and mortality. Multiple logistic regression analysis showed that older age and laparoscopic technique were associated with higher complications after surgery. CONCLUSION: The use of the Da Vinci Xi robot in our institution was associated with improved outcomes compared to laparoscopic hiatal hernia repair despite a higher incidence of re-operative cases in the robotic group. Thus, short-term outcomes of Da Vinci Xi robot-assisted hiatal hernia repair are not inferior to laparoscopic hiatal hernia repair. Further studies are needed to determine if Da Vinci Xi robot provides superior short-term and long-term outcome in treatment of symptomatic hiatal hernia.
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Fundoplicación/métodos , Hernia Hiatal/cirugía , Herniorrafia/métodos , Laparoscopía/métodos , Procedimientos Quirúrgicos Robotizados/métodos , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Periodo Posoperatorio , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
BACKGROUND: Achalasia is an uncommon disease treated by decreasing the lower esophageal sphincter resting pressure. This study compared the safety and efficacy of esophago-gastric myotomy via laparoscopic, robotic, and per-oral endoscopic approaches. METHODS: A retrospective review of data on patients with achalasia or other esophageal dysmotility disorder undergoing laparoscopic, robotically assisted, or per-oral endoscopic myotomy (POEM) procedures between 2013 and 2017 was performed. Patient demographics, comorbidities, procedure details, length of stay, 30-day readmission rate, and combined technical complication (full-thickness injury, conversion to open, and delayed perforation) were compared. Multiple logistic regression analysis was performed to determine which factors contributed to combined technical complication. RESULTS: There were 171 patients who underwent esophago-gastric myotomy with 161 (94.2%) having achalasia. There were 40 laparoscopic Heller myotomies with partial fundoplication, 44 robotic Heller myotomies with partial fundoplication, and 87 POEM procedures performed during the study period. Baseline statistical differences were found among the groups in regard to gastroesophageal reflux symptoms, arrhythmia, hypertension, and congestive heart failure. Laparoscopic Heller myotomy had significantly higher combined technical complications (7, 17.5%) compared to robotically assisted Heller myotomy (0, 0%) and POEM (1, 1.1%). Multivariate analysis showed that laparoscopic Heller myotomy (OR 32.22; 95% CI 2.66, 389.83; p = 0.01), myocardial infarction (OR 27.94; 95% CI 1.66, 471.10; p = 0.02), and history of smoking (OR 8.87; 95% CI 1.29, 61.15; p = 0.03) were risks for developing combined technical complications. CONCLUSION: Robotically assisted Heller myotomy and POEM are safe and efficacious treatments for achalasia with lower rates of technical complications compared to laparoscopic Heller myotomy. With the advancements in endoscopic instruments and robotic surgery, POEM and robotically assisted Heller myotomy should be considered in the treatment of achalasia and esophageal dysmotility disorders.
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Acalasia del Esófago/cirugía , Miotomía de Heller/métodos , Laparoscopía/métodos , Piloromiotomia/métodos , Procedimientos Quirúrgicos Robotizados/métodos , Esfínter Esofágico Inferior/cirugía , Femenino , Fundoplicación/métodos , Miotomía de Heller/efectos adversos , Humanos , Laparoscopía/efectos adversos , Tiempo de Internación/estadística & datos numéricos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Readmisión del Paciente/estadística & datos numéricos , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Piloromiotomia/efectos adversos , Estudios Retrospectivos , Procedimientos Quirúrgicos Robotizados/efectos adversos , Resultado del TratamientoRESUMEN
BACKGROUND: Metastasis is the main cause of death for lung cancer patients. The ex vivo 4D acellular lung model has been shown to mimic this metastatic process. However, the main concern is the model's lack of cellular components of the tumor's microenvironment. In this study, we aim to determine if the intact lung microenvironment will still allow lung cancer metastasis to form. METHODS: We harvested a heart-lung block from a rat and placed it in a bioreactor after cannulating the pulmonary artery, trachea and tying the right main bronchus for 10-15 days without any tumor cells as a control group or with NSCLC (A549, H1299 or H460), SCLC (H69, H446 or SHP77) or breast cancer cell lines (MCF7 or MDAMB231) through the trachea. We performed lobectomy, H&E staining and IHC for human mitochondria to determine the primary tumor's growth and formation of metastatic lesions. In addition, we isolated circulating tumor cells (CTC) from the model seeded with GFP tagged cells. RESULTS: In the control group, no gross tumor nodules were found, H&E staining showed hyperplastic cells and IHC showed no staining for human mitochondria. All of the models seeded with cancer cell lines formed gross primary tumor nodules that had microscopic characteristics of human cancer cells on H&E staining with IHC showing staining for human mitochondria. CTC were isolated for those cells labeled with GFP and they were viable in culture. Finally, all cell lines formed metastatic lesions with cells stained for human mitochondria. CONCLUSION: The cellular ex vivo 4D model shows that human cancer cells can form a primary tumor, CTC and metastatic lesions in an intact cellular environment. This study suggests that the natural matrix scaffold is the only necessary component to drive metastatic progression and that cellular components play a role in modulating tumor progression.
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Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Células Pequeñas/patología , Neoplasias Pulmonares/patología , Animales , Línea Celular Tumoral , Modelos Animales de Enfermedad , Progresión de la Enfermedad , Humanos , Masculino , Metástasis de la Neoplasia , Células Neoplásicas Circulantes/patología , Ratas , Carga TumoralRESUMEN
BACKGROUND: Primary laparoscopic hiatal repair with fundoplication is associated with a high recurrence rate. We wanted to evaluate the potential risks posed by routine use of onlay-mesh during hiatal closure, when compared to primary repair. METHODS: Utilizing single-institutional database, we identified patients who underwent primary laparoscopic hiatal repair from January 2005 through December 2014. Retrospective chart review was performed to determine perioperative morbidity and mortality. Long-term results were assessed by sending out a questionnaire. Results were tabulated and patients were divided into 2 groups: fundoplication with hiatal closure + absorbable or non-absorbable mesh and fundoplication with hiatal closure alone. RESULTS: A total of 505 patients underwent primary laparoscopic fundoplication. Mesh reinforcement was used in 270 patients (53.5%). There was no significant difference in the 30-day perioperative outcomes between the 2 groups. No clinically apparent erosions were noted and no mesh required removal. Standard questionnaire was sent to 475 patients; 174 (36.6%) patients responded with a median follow-up of 4.29 years. Once again, no difference was noted between the 2 groups in terms of dysphagia, heartburn, long-term antacid use, or patient satisfaction. Of these, 15 patients (16.9%, 15/89) in the 'Mesh' cohort had symptomatic recurrence as compared to 19 patients (22.4%, 19/85) in the 'No Mesh' cohort (p = 0.362). A reoperation was necessary in 6 patients (6.7%) in the 'Mesh' cohort as compared to 3 patients (3.5%) in the 'No Mesh' cohort (p = 0.543). CONCLUSIONS: Onlay-mesh use in laparoscopic hiatal repair with fundoplication is safe and has similar short and long-term results as primary repair.
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Hernia Hiatal/cirugía , Mallas Quirúrgicas , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Estudios de Seguimiento , Fundoplicación , Humanos , Laparoscopía , Masculino , Persona de Mediana Edad , Satisfacción del Paciente , Recurrencia , Reoperación/estadística & datos numéricos , Estudios Retrospectivos , Encuestas y Cuestionarios , Adulto JovenRESUMEN
BACKGROUND: Breast cancer mortality is most common in cancer in women, and there are no ex vivo models that can capture the primary growth of tumor with fidelity to the in vivo tumor growth. In this study, we grew human breast cancer cell lines in an acellular lung matrix of the ex vivo four-dimensional lung model to determine if they form primary tumor and the extent to which they mimic the histology and characteristics of the human tumors. MATERIALS AND METHODS: Rat lungs were harvested, decellularized, and placed in a bioreactor. To study the primary tumor growth, we seeded the lung via the trachea with human breast cancer cells SUM159, MCF7, or MDMB231 and perfused the pulmonary artery with oxygenated media. Lobectomies were performed and processed for hematoxylin and eosin, Ki-67, caspase-3, estrogen receptor, and progesterone receptor antibodies. RESULTS: All three cell lines grew in the ex vivo four-dimensional model and formed perfusable tumor nodules with similar histology and morphology as the primary tumors. SUM159 and MDAMB231 showed higher proliferation and apoptotic indices than MCF7. In addition, MCF7 retained its estrogen receptor and progesterone receptor positivity, whereas SUM159 and MDAMB 231 did not have any staining. CONCLUSIONS: Overall, our study showed that human breast cancer cells can be grown on the ex vivo four-dimensional lung model, which then form primary tumor nodules that mimic the morphology and histology of the original tumor.
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Neoplasias de la Mama/patología , Pulmón/patología , Animales , Apoptosis , Biomarcadores de Tumor/metabolismo , Reactores Biológicos , Neoplasias de la Mama/metabolismo , Línea Celular Tumoral , Proliferación Celular , Femenino , Humanos , Técnicas In Vitro , Masculino , Invasividad Neoplásica , Ratas , Ratas Sprague-DawleyRESUMEN
BACKGROUND: Currently, there is no in vitro or ex vivo model that can isolate circulating tumor cells (CTCs). Recently, we developed a four-dimensional (4D) lung cancer model that allows for the isolation of CTCs. We postulated that these cells have different properties than parental (2D) cells. MATERIALS AND METHODS: We obtained CTCs by growing A549, H1299, 393P, and 344SQ cell lines on the 4D lung model. The CTCs were functionally characterized in vitro and gene expression of the cell adhesion molecules was compared with respective 2D cells. Integrin beta 4 (ITGB4) was further investigated by stably transfecting the A549 and H1299 cells. RESULTS: We found that all cell lines produced CTCs, and that CTCs from the 4D model were less adherent to the plastic and have a slower growth rate than respective 2D cells (P < 0.01). Most of the cell adhesion molecules were downregulated (P < 0.05) in CTCs, and ITGB4 was the common molecule, significantly more underexpressed in CTCs from all cell lines than their respective 2D cells. The modulation of ITGB4 led to a differential function of 2D cells. CONCLUSIONS: CTCs from the 4D model have different transcriptional, translational, and in vitro characteristics than the same cells grown on a petri dish, and these CTCs from the 4D model have the properties of CTCs that are responsible for metastasis.
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Integrina beta4/metabolismo , Células Neoplásicas Circulantes/metabolismo , Animales , Adhesión Celular , Moléculas de Adhesión Celular/metabolismo , Técnicas de Cultivo de Célula , Línea Celular Tumoral , Humanos , Técnicas In Vitro , RatasRESUMEN
The tumor microenvironment plays an important role in regulating cell growth and metastasis. Recently, we developed an ex vivo lung cancer model (four dimensional, 4D) that forms perfusable tumor nodules on a lung matrix that mimics human lung cancer histopathology and protease secretion pattern. We compared the gene expression profile (Human OneArray v5 chip) of A549 cells, a human lung cancer cell line, grown in a petri dish (two-dimensional, 2D), and of the same cells grown in the matrix of our ex vivo model (4D). Furthermore, we obtained gene expression data of A549 cells grown in a petri dish (2D) and matrigel (three-dimensional, 3D) from a previous study and compared the 3D expression profile with that of 4D. Expression array analysis showed 2,954 genes differentially expressed between 2D and 4D. Gene ontology (GO) analysis showed upregulation of several genes associated with extracellular matrix, polarity and cell fate and development. Moreover, expression array analysis of 2D vs. 3D showed 1,006 genes that were most differentially expressed, with only 36 genes (4%) having similar expression patterns as observed between 2D and 4D. Finally, the differential gene expression signature of 4D cells (vs. 2D) correlated significantly with poor survival in patients with lung cancer (n = 1,492), while the expression signature of 3D vs. 2D correlated with better survival in lung cancer patients with lung cancer. As patients with larger tumors have a worse rate of survival, the ex vivo 4D model may be a good mimic of natural progression of tumor growth in lung cancer patients.
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Adenocarcinoma/mortalidad , Biomarcadores de Tumor/genética , Carcinoma Basocelular/mortalidad , Técnicas de Cultivo de Célula , Modelos Animales de Enfermedad , Perfilación de la Expresión Génica , Neoplasias Pulmonares/mortalidad , Adenocarcinoma/genética , Adenocarcinoma/metabolismo , Animales , Animales Recién Nacidos , Biomarcadores de Tumor/metabolismo , Western Blotting , Carcinoma Basocelular/genética , Carcinoma Basocelular/metabolismo , Humanos , Técnicas para Inmunoenzimas , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Análisis de Secuencia por Matrices de Oligonucleótidos , Pronóstico , ARN Mensajero/genética , Ratas , Reacción en Cadena en Tiempo Real de la Polimerasa , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Tasa de Supervivencia , Células Tumorales CultivadasRESUMEN
The incidence of esophageal cancer remains on the rise worldwide and despite aggressive research in the field of gastrointestinal oncology, the survival remains poor. Much remains to be defined in esophageal cancer, including the development of an effective screening tool, identifying a good tumor marker for surveillance purposes, ways to target esophageal cancer stem cells as well as circulating tumor cells, and developing minimally invasive protocols to treat early-stage disease. The goal of this chapter is to highlight some of the recent advances and ongoing research in the field of esophageal cancer.
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DISCLAIMER: In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. PURPOSE: The objectives of this study were to identify the most performed surgical procedures associated with the highest rates of discharge opioid overprescribing and to implement an electronic health record (EHR) alert to reduce discharge opioid overprescribing. METHODS: This quality improvement, before-and-after study included patients undergoing one of the identified target procedures-laparoscopic cholecystectomy, unilateral open inguinal hernia repair, and laparoscopic appendectomy-at an academic medical center. The alert notified providers when the prescribed opioid quantity exceeded guideline recommendations. The preimplementation cohort included surgical encounters from January 2020 to December 2021. The EHR alert was implemented in May 2022 following provider education via email and in-person presentations. The postimplementation cohort included surgical encounters from May to August 2022. The primary outcome was the proportion of patients with a discharge opioid supply exceeding guideline recommendations (overprescribing). RESULTS: A total of 1,478 patients were included in the preimplementation cohort, and 141 patients were included in the postimplementation cohort. The rate of discharge opioid overprescribing decreased from 48% in the preimplementation cohort to 3% in the postimplementation cohort, with an unadjusted absolute reduction of 45% (95% confidence interval, 41% to 49%; P < 0.001) and an adjusted odds ratio of 0.03 (95% confidence interval, 0.01 to 0.08; P < 0.001). Among patients who received opioids, the mean (SD) opioid supply at discharge decreased from 92 (43) oral morphine milligram equivalents (MME) (before implementation) to 57 (20) MME (after implementation) (P < 0.001). The proportion of patients who received additional opioid prescriptions within 1 to 14 days of hospital discharge did not change (P = 0.76). CONCLUSION: Implementation of an EHR alert along with provider education can reduce discharge opioid overprescribing following general surgery.
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Gastroesophageal reflux disease (GERD) is among the most prevalent diseases in the United States. Mainstay therapy is lifestyle modification and medical therapy. If patients have GERD despite medical therapy, appropriate testing should be performed to determine if surgical or endoscopic therapy will provide improvement in their symptoms. Gold standard therapy is a minimally invasive fundoplication. Patients with body mass index <35, small or no hiatal hernia, normal motility, and pathologic GERD should consider magnetic sphincter augmentation. If a patient is not interested in either fundoplication or MSA, they should consider endoscopic treatment with either STRETTA or Transoral Incisionless fundoplication 2.0. A meta-analysis by Gong and colleagues showed that endoscopic treatments are better compared with medical therapy but are worse than surgical therapy.
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Reflujo Gastroesofágico , Hernia Hiatal , Laparoscopía , Humanos , Reflujo Gastroesofágico/diagnóstico , Fundoplicación , Hernia Hiatal/cirugía , Calidad de Vida , Resultado del TratamientoRESUMEN
Performing robotic thoracic lung resection is becoming an option for patients with complex thoracic disease. The robotic-assisted approach has similar survival with decreased postoperative pain, morbidity, and hospital length of stay compared with the open approach in pneumonectomy, bronchoplasty, and arterioplasty. Appropriate patient selection based on medical and surgical history combined with surgeon experience is imperative for an excellent outcome. This article will discuss the use of the robot in pneumonectomy, arterioplasty, and bronchoplasty to provide information about the technical approach and postoperative management.
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Neoplasias Pulmonares , Procedimientos Quirúrgicos Robotizados , Robótica , Humanos , Neoplasias Pulmonares/cirugía , Estudios Retrospectivos , Neumonectomía , Pulmón , Cirugía Torácica Asistida por Video , Resultado del TratamientoRESUMEN
BACKGROUND: Medical students and general surgery residents often do not get exposure to cardiothoracic surgery (CTS) because of a decreased emphasis on CTS rotations during their training. The Southern Thoracic Surgical Association (STSA) began offering the Brooks Scholarship to medical students in 2010 and general surgery residents in 2014 to promote CTS. This study examines the impact of the scholarship. METHODS: We examined the history of the award and how STSA administers the award. Next we examined the impact of the award by evaluating the number of medical students and residents who are tracked to complete a CTS program. Finally we performed an analysis of the academic output of the awardees who have completed or were tracked to complete a CTS program. RESULTS: The scholarship was developed to honor the memory of past STSA President Dr James W. Brooks. The award is administered through the STSA scholarship committee and provides medical students and residents funds to attend the STSA annual meeting and the opportunity to spend time with a mentor during the meeting. Eighty-eight percent of medical student recipients (21/24) and 100% of general surgery resident recipients (15/15) have completed or are on track to complete a CTS program. The 36 recipients going into CTS have published a total of 823 papers and 9240 articles have cited those papers. CONCLUSIONS: The STSA medical student and general surgery Brooks scholarship awards were associated with completing or pursuing a career in CTS. STSA should continue the Brooks scholarship to attract talented medical students and residents to CTS.
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Distinciones y Premios , Internado y Residencia , Estudiantes de Medicina , Cirugía Torácica , Procedimientos Quirúrgicos Torácicos , Humanos , BecasRESUMEN
Background: As of the most recent surveys of resident programs in 2018, only slightly more than half of programs have formal robotic training curriculums implemented. Fewer programs have further assessed their own curriculum and its benefit. Method: We conducted a PubMed/MEDLINE literature search for robotic surgery curriculums and those that had assessment of their programs. Results: A total of 11 studies were reviewed. When reviewed in chronological order, there has been a progression towards more robotic specific objective data analysis as opposed to subjective surveying. There is a wide variation in curriculums, but simulation use is pervasive. Conclusions: Our review makes evident two important concepts-there is great variety in training curriculums and there is great benefit in implementation. The importance is in establishment of what makes resident training effective and supports the adaptable and successful surgeon. This may come from an adaptable curriculum but a structured test-out assessment.