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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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Recuperação Pós-Cirúrgica Melhorada , Laparoscopia , Transplante de Pulmão , Procedimentos Cirúrgicos Robóticos , Humanos , Fundoplicatura/métodos , Procedimentos Cirúrgicos Robóticos/efeitos adversos , Procedimentos Cirúrgicos Robóticos/métodos , Estudos Retrospectivos , Transplante de Pulmão/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/prevenção & controle , Laparoscopia/efeitos adversos , Laparoscopia/métodos , Tempo de InternaçãoRESUMO
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 Neuroendócrino , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Carcinoma Neuroendócrino/patologia , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Humanos , Estadiamento de Neoplasias , Pneumonectomia , Estudos RetrospectivosRESUMO
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 Esofágica , Miotomia de Heller , Hérnia Hiatal , Laparoscopia , Acalasia Esofágica/diagnóstico , Acalasia Esofágica/cirurgia , Fundoplicatura/métodos , Hérnia Hiatal/diagnóstico , Hérnia Hiatal/cirurgia , Humanos , Laparoscopia/métodos , Resultado do TratamentoRESUMO
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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Transtornos de Deglutição , Hérnia Hiatal , Laparoscopia , Transtornos de Deglutição/etiologia , Transtornos de Deglutição/cirurgia , Junção Esofagogástrica/cirurgia , Fundoplicatura/métodos , Hérnia Hiatal/complicações , Hérnia Hiatal/cirurgia , Herniorrafia , Humanos , Resultado do TratamentoRESUMO
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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Refluxo Gastroesofágico , Hérnia Hiatal , Laparoscopia , Fundoplicatura , Refluxo Gastroesofágico/cirurgia , Hérnia Hiatal/cirurgia , Herniorrafia , Humanos , Estudos Retrospectivos , Resultado do TratamentoRESUMO
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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Fundoplicatura/métodos , Hérnia Hiatal/cirurgia , Herniorrafia/métodos , Laparoscopia/métodos , Procedimentos Cirúrgicos Robóticos/métodos , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Período Pós-Operatório , Estudos Retrospectivos , Resultado do TratamentoRESUMO
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 Esofágica/cirurgia , Miotomia de Heller/métodos , Laparoscopia/métodos , Piloromiotomia/métodos , Procedimentos Cirúrgicos Robóticos/métodos , Esfíncter Esofágico Inferior/cirurgia , Feminino , Fundoplicatura/métodos , Miotomia de Heller/efeitos adversos , Humanos , Laparoscopia/efeitos adversos , Tempo de Internação/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Readmissão do Paciente/estatística & dados numéricos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Piloromiotomia/efeitos adversos , Estudos Retrospectivos , Procedimentos Cirúrgicos Robóticos/efeitos adversos , Resultado do TratamentoRESUMO
BACKGROUND: Clinical xenotransplantation is not possible because humans possess antibodies that recognize antigens on the surface of pig cells. Galα-1,3-Gal (Gal) and N-glycolylneuraminic acid (Neu5Gc) are two known xenoantigens. METHODS: We report the homozygous disruption of the α1, 3-galactosyltransferase (GGTA1) and the cytidine monophosphate-N-acetylneuraminic acid hydroxylase (CMAH) genes in liver-derived female pig cells using zinc-finger nucleases (ZFNs). Somatic cell nuclear transfer (SCNT) was used to produce healthy cloned piglets from the genetically modified liver cells. Antibody-binding and antibody-mediated complement-dependent cytotoxicity assays were used to examine the immunoreactivity of pig cells deficient in Neu5Gc and Gal. RESULTS: This approach enabled rapid production of a pig strain deficient in multiple genes without extensive breeding protocols. Immune recognition studies showed that pigs lacking both CMAH and GGTA1 gene activities reduce the humoral barrier to xenotransplantation, further than pigs lacking only GGTA1. CONCLUSIONS: This technology will accelerate the development of pigs for xenotransplantation research.
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Dissacarídeos/imunologia , Ácidos Neuramínicos/imunologia , Sus scrofa/genética , Sus scrofa/imunologia , Transplante Heterólogo/imunologia , Animais , Anticorpos Heterófilos/metabolismo , Citotoxicidade Celular Dependente de Anticorpos , Antígenos Heterófilos/imunologia , Antígenos Heterófilos/metabolismo , Sequência de Bases , Células Cultivadas , DNA/genética , Dissacarídeos/deficiência , Feminino , Galactosiltransferases/deficiência , Galactosiltransferases/genética , Técnicas de Inativação de Genes/métodos , Humanos , Leucócitos Mononucleares/imunologia , Oxigenases de Função Mista/deficiência , Oxigenases de Função Mista/genética , Ácidos Neuramínicos/metabolismo , Sus scrofa/metabolismoRESUMO
BACKGROUND: Antibody-mediated rejection continues to be an obstacle for xenotransplantation despite development of α1,3-galactosyltransferase knockout (GTKO) pigs. Fibronectin (Fn) from GTKO pigs was identified as a xenoantigen in baboons. N-glycolylneuraminic acid (Neu5Gc), similar to galactose α1,3-galactose, is an antigenic carbohydrate found in pigs. We evaluated human antibody reactivity and performed initial antigenic epitope characterization of Fn from GTKO pigs. MATERIALS AND METHODS: GTKO pig aortic endothelial cells (AEC) were isolated and assessed for antibody-mediated complement-dependent cytotoxicity (CDC). Human and GTKO pig Fn were purified and analyzed using immunoblots. GTKO pig and human AEC absorbed human sera were assessed for CDC and anti-GTKO pig Fn antibodies. GTKO pig proteins were assessed for Neu5Gc. Immunoaffinity-purified human IgG anti-GTKO pig (hIgG-GTKOp) Fn using a GTKO pig Fn column were evaluated for cross-reactivity with other proteins. RESULTS: GTKO pig AEC had greater human antibody binding, complement deposition and CDC compared with allogeneic human AEC. Human sera absorbed with GTKO pig AEC resulted in diminished anti-GTKO pig Fn antibody. Neu5Gc was identified on GTKO pig Fn and other proteins. The hIgG-GTKOp Fn cross-reacted with multiple GTKO pig proteins and was enriched with anti-Neu5Gc antibody. CONCLUSIONS: Removal of antigenic epitopes from GTKO pig AEC would improve xenograft compatibility. GTKO pig Fn has antigenic epitopes, one identified as Neu5Gc, which may be responsible for pathology and cross-reactivity of hIgG-GTKOp Fn. Genetic knockout of Neu5Gc appears necessary to address significance and identification of non-Neu5Gc GTKO pig Fn antigenic epitopes.
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Antígenos Heterófilos/imunologia , Fibronectinas/imunologia , Galactosiltransferases/deficiência , Galactosiltransferases/genética , Suínos/imunologia , Transplante Heterólogo , Animais , Animais Geneticamente Modificados , Anticorpos/imunologia , Aorta/citologia , Aorta/imunologia , Células Cultivadas , Reações Cruzadas/imunologia , Endotélio Vascular/citologia , Endotélio Vascular/imunologia , Epitopos/imunologia , Técnicas de Inativação de Genes , Humanos , Modelos Animais , Suínos/genéticaRESUMO
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.
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BACKGROUND: Stellate ganglion blockade (SGB) can control ventricular arrhythmias (VAs), but outcomes are unclear. Percutaneous stellate ganglion (SG) recording and stimulation in humans has not been reported. OBJECTIVE: The purpose of this study was to assess the outcomes of SGB and the feasibility of SG stimulation and recording in humans with VAs. METHODS: Two patient cohorts were included-group 1: patients undergoing SGB for drug-refractory VAs. SGB was performed by injection of liposomal bupivacaine. Incidence of VAs at 24 and 72 hours and clinical outcomes were collected; group 2: patients undergoing SG stimulation and recording during VA ablation; a 2-F octapolar catheter was placed at the SG at the C7 level. Recording (30 kHz sampling, 0.5-2 kHz filter) and stimulation (up to 80 mA output, 50 Hz, 2 ms pulse width for 20-30 seconds) was performed. RESULTS: Group 1 included 25 patients [age 59.2 ± 12.8 years; 19 (76%) men] who underwent SGB for VAs. Nineteen patients (76.0%) were free of VA up to 72 hours postprocedure. However, 15 (60.0%) had VAs recurrence for a mean of 5.47 ± 4.52 days. Group 2 included 11 patients (mean age 63 ± 12.7 years; 82.7% men). SG stimulation caused consistent increases in systolic blood pressure. We recorded unequivocal signals with temporal association with arrhythmias in 4 of 11 patients. CONCLUSION: SGB provides short-term VA control, but has no benefit in the absence of definitive VA therapies. SG recording and stimulation is feasible and may have value to elicit VA and understand neural mechanisms of VA in the electrophysiology laboratory.
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Bloqueio Nervoso Autônomo , Gânglio Estrelado , Masculino , Humanos , Pessoa de Meia-Idade , Idoso , Feminino , Arritmias Cardíacas , Bloqueio Nervoso Autônomo/métodos , Pressão SanguíneaRESUMO
BACKGROUND: Atrioesophageal fistula is a rare and morbid complication of ablation therapy for atrial fibrillation. Surgery provides increased survival; however, which surgical approach provides the best outcome is unclear. METHODS: We performed a retrospective analysis of cases in the literature and at our institution. We characterized patients by presenting symptoms, diagnostic method, surgical therapy with different approaches, and survival. RESULTS: In total, 219 patients were found, with 216 patients identified from 122 papers in the literature and 3 patients from our institutional database (2000-2022). The most common presenting symptoms included fever/chill (71.8%) and neurologic deficiency (62.9%). The overall survival for this cohort was 47%. Patients who had an operation had significantly improved survival compared with those who did not have an operation (71.9.3% vs 11%, P < .001). Patients who survived after surgical intervention typically underwent right thoracotomy (45.1%), patch repair of the left atrium (61.1%), and primary repair of the esophagus (68.3%) on cardiopulmonary bypass (84.8%) with a flap between the 2 organs (84.6%). Patients who had cardiopulmonary bypass had increased survival (39 of 45 [86.7%]) compared with those who did not have cardiopulmonary bypass (7 of 17 [41.2%], P < .001). CONCLUSIONS: Patients with atrioesophageal fistula should undergo surgical intervention. A patch repair of the left atrium and primary repair of the esophagus with a flap between the organs during cardiopulmonary bypass is the most common successful repair. Cardiopulmonary bypass may allow better débridement and repair of the left atrium, which may provide a survival advantage in the treatment of this rare disease.
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Fibrilação Atrial , Ablação por Cateter , Fístula Esofágica , Cardiopatias , Humanos , Fístula Esofágica/diagnóstico , Fístula Esofágica/etiologia , Fístula Esofágica/cirurgia , Estudos Retrospectivos , Cardiopatias/etiologia , Cardiopatias/cirurgia , Cardiopatias/diagnóstico , Ablação por Cateter/efeitos adversos , Fibrilação Atrial/cirurgia , Fibrilação Atrial/complicações , Átrios do Coração/cirurgiaRESUMO
BACKGROUND: Acute thrombocytopenia was revealed as a limiting factor to porcine liver xenotransplantation from in vitro and in vivo studies using porcine liver in human and baboon transplant models. The asialoglycoprotein receptor 1 (ASGR1) on liver sinusoidal endothelial cells (LSEC) and macrophage antigen complex-1 (Mac-1) on Kupffer cells (KC) mediate platelet phagocytosis and have carbohydrate-binding sites that recognize galactose and N-acetyl glucosamine in the beta conformation. Analysis of these receptor carbohydrate-binding domains and surface carbohydrates on human and porcine platelets may shed light on the mechanism of xenotransplantation-induced thrombocytopenia. METHODS: An amino acid sequence comparison of human and porcine ASGR1 lectin-binding domains was performed. Using fluorescent labeled-lectins, human platelets, domestic and α1,3 galactosyltransferase knockout/human decay accelerating factor, porcine platelets were characterized by flow cytometry and lectin blot analyses. After desialylation, human and porcine platelets were examined by flow cytometry to determine whether sialic acid capping of galactose and N-acetyl glucosamine oligosaccharides in the beta conformation was a factor. Further, desialylated human platelets were studied on primary porcine liver sinusoidal cells with regard to binding and phagocytosis. RESULTS: Human platelets have four times more exposed galactose ß1-4 N-acetyl glucosamine (Galß) and N-acetyl glucosamine ß1-4 N-acetyl glucosamine (ßGlcNAc) than fresh porcine platelets. Galß and ßGlcNAc moieties on porcine platelets were not masked by sialic acid. Removal of sialic acid from human platelets increased binding and phagocytosis by LSEC and KC. CONCLUSIONS: Differences between human and porcine ASGR1 and Mac-1, in combination with a significantly higher number of galactose and N-acetyl glucosamine-containing oligosaccharides on human platelets contribute, in part, to platelet loss seen in porcine liver xenotransplantation.
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Acetilglucosamina/metabolismo , Receptor de Asialoglicoproteína/metabolismo , Plaquetas/metabolismo , Fígado/metabolismo , Oligossacarídeos/metabolismo , Fagocitose/fisiologia , Acetilglucosamina/química , Sequência de Aminoácidos , Animais , Receptor de Asialoglicoproteína/química , Antígenos CD11/análise , Galactose/química , Galactose/metabolismo , Humanos , Técnicas In Vitro , Células de Kupffer/metabolismo , Lectinas/metabolismo , Fígado/citologia , Transplante de Fígado/fisiologia , Antígeno de Macrófago 1/química , Antígeno de Macrófago 1/metabolismo , Dados de Sequência Molecular , Ácido N-Acetilneuramínico/metabolismo , Contagem de Plaquetas , Análise de Sequência de Proteína , Especificidade da Espécie , Suínos , Trombocitopenia/etiologia , Transplante HeterólogoRESUMO
BACKGROUND: Xenotransplantation has the potential to solve the critical shortage of human organs available for allotransplantation. The major barrier to porcine liver xenotransplantation is sequestration of human platelets causing thrombocytopenia. Porcine liver sinusoidal endothelial cells (LSEC) bind and phagocytose human platelets at least in part through binding of the asialoglycoprotein receptor 1 (ASGR1). Our purpose was to generate an immortalized porcine LSEC (iLSEC) line that mimics primary LSEC in ASGR1 expression and phagocytosis of human platelets. Porcine iLSEC would enable continued study of xenotransplantation-induced thrombocytopenia in vitro with fewer animals sacrificed. METHODS: Primary domestic porcine LSEC were transduced with lentiviral vector expressing the large and small T antigen of SV40 (SV40 TAg). The phenotype and genotype of the immortalized LSEC were compared with primary LSEC. RESULTS: A total of eight clones expressing SV40 TAg were isolated, and one clone was subcultured and analyzed for growth, phenotype, and function during passages 15-40. Expression of the SV40 TAg was confirmed by confocal microscopy and western blot. MTS cell proliferation assay demonstrated that the clone rapidly grew in culture medium with 2-10% fetal bovine serum. iLSEC expressed the endothelial cell marker, CD31, as determined by confocal microscopy and flow cytometry. Activation of iLSEC by treatment with lipopolysaccharide (LPS) resulted in upregulation of the inflammatory cytokine interleukin 6 (IL 6) by qPCR and ELISA. iLSEC phagocytosed human serum albumin and latex beads as measured by flow cytometry. Human platelets were phagocytosed by immortalized porcine LSEC. CONCLUSIONS: Immortalized porcine LSEC retain a phagocytic phenotype, making them a good model for the study of xenotransplantation-induced thrombocytopenia and may provide further insight into the phagocytic role of LSEC.
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Hepatócitos/transplante , Trombocitopenia/etiologia , Transplante Heterólogo/efeitos adversos , Animais , Antígenos Transformantes de Poliomavirus/genética , Receptor de Asialoglicoproteína/metabolismo , Plaquetas/metabolismo , Bovinos , Linhagem Celular Transformada , Proliferação de Células , Células Endoteliais/fisiologia , Células Endoteliais/transplante , Hepatócitos/fisiologia , Humanos , Técnicas In Vitro , Interleucina-6/metabolismo , Fígado/citologia , Modelos Biológicos , Fagocitose , Sus scrofa , SuínosRESUMO
BACKGROUND: Human preformed antibodies continue to recognize porcine xenografts, despite the advent of α-galactosyltransferase knockout (GTKO) pigs. This study examined the potential reactivity of human preformed IgG and IgM antibodies toward antigens in the GTKO pig liver. METHODS: Human serum was analyzed for the concentration of IgG, IgM, anti-αgal antibody, anti-non-αgal antibody and cytotoxicity toward domestic and GTKO fibroblasts and liver sinusoidal endothelial cells (LSEC). We detected preformed antibodies in human serum directed toward GTKO pig liver cells and tissue samples using advanced proteomic techniques. The targets of preformed antibodies were identified by MALDI TOF TOF mass spectrometry and validated by confocal microscopy, immunoblot, and immunoprecipitation. RESULTS: Human serum used in this study contained 2.06 µg/ml IgG and 0.013 µg/ml IgM directed toward GTKO fibroblasts. Human IgG and IgM bound to GTKO LSEC in a dose-dependent manner and were cytotoxic. We detected 357 protein spots recognized by human IgG and 233 by human IgM. Two hundred and nineteen proteins were common to both human IgG and IgM. Mass spectrometry identified numerous immunoreactive proteins, of which 19 were membrane proteins on liver cells. The most significant to this study were α-enolase, CFTR, and E-cadherin, which were abundant in GTKO pig tissues and expressed on the surface of GTKO LSEC. Human IgG captured α-enolase, CFTR, and E-cadherin by immunoprecipitation validating the proteomic identification. CONCLUSION: These experiments indicate that several membrane antigens in GTKO pigs could be recognized directly by human IgG or IgM. Further studies on the contribution of these antigens to antibody-mediated xenograft rejection are necessary.
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Anticorpos Heterófilos/sangue , Galactosiltransferases/deficiência , Galactosiltransferases/genética , Sus scrofa/genética , Sus scrofa/imunologia , Animais , Animais Geneticamente Modificados , Citotoxicidade Celular Dependente de Anticorpos , Antígenos Heterófilos , Proteínas do Sistema Complemento/metabolismo , Células Endoteliais/imunologia , Galactosiltransferases/imunologia , Técnicas de Inativação de Genes , Rejeição de Enxerto/etiologia , Rejeição de Enxerto/imunologia , Hepatócitos/imunologia , Humanos , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Proteômica , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Transplante Heterólogo/efeitos adversos , Transplante Heterólogo/imunologia , Trissacarídeos/imunologiaRESUMO
Background: Surgical videos allow residents to prepare for the operating room. We sought to determine if a video-based curriculum improves resident participation during robot-assisted surgery. Methods: We created a video-based surgical curriculum by providing residents with narrated videos of similar cases before participating in the operating room. We obtained information about the average monthly viewings of cases and the total monthly time spent viewing cases. We surveyed the residents after a year of the program. In addition, we used software to track the amount of time the resident spent controlling the robot during the case. We assessed the amount of time the resident had control of the robot for their first robot-assisted hiatal hernia repair of the month with a dual console for 13 months before and after implementing the curriculum. Results: A total of 43 videos were made for the video-based curriculum. On average, 37 videos were viewed during the month, with residents spending 16 hours per month viewing the videos. Twenty residents (83%) completed the survey. 90% of the residents often or always watched the video before surgery. All residents felt videos were better than books to prepare for surgery (100%). Residents thought that the videos helped them prepare for surgery: understanding surgical anatomy (95%), the cognitive aspect of the surgery (95%), and the technical part of surgery (100%). Analysis of the resident console time of the first robot-assisted hiatal hernia repair of the month showed a significant increase in the amount of time the resident participated in the case from 11% to 48% (P<0.001). Conclusions: Video-based curriculum was a valuable tool for residents to prepare for surgical cases. Video-based curriculum significantly increases resident participation during robot-assisted thoracic surgery. Adopting this strategy will improve the resident training experience. A video-based curriculum should be adopted in surgical education.
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A 79-year-old male former smoker presented with a T4 (>7 cm) adenocarcinoma of the right upper lobe. The patient was staged at clinical T4N0M0 and underwent robot-assisted right upper lobectomy and mediastinal lymph node dissection. The patient was discharged home on postoperative day 3. Larger tumors are a relative contraindication for video-assisted thoracoscopic surgical lobectomy. The robot platform overcomes the technical limitations of video-assisted thoracoscopic surgery and allows for the successful resection of large tumors.
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Neoplasias Pulmonares , Robótica , Idoso , Humanos , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/cirurgia , Excisão de Linfonodo , Masculino , Pneumonectomia , Cirurgia Torácica VídeoassistidaRESUMO
Background: Open and video-assisted thoracoscopic surgery (VATS) pulmonary lobectomy requires a skilled assistant to complete the operation. A potential benefit of a robot is to allow a surgeon to complete the operation autonomously. We sought to determine the safety of performing robotic-assisted pulmonary lobectomy with self-assistance. Methods: We performed a retrospective analysis of self-assisting robot-assisted lobectomy. We evaluated the intraoperative and postoperative outcomes. We compared the outcome to the propensity matched group of patients who had VATS lobectomy. We also compared them to published outcomes of robot-assisted lobectomy. Results: 95 patients underwent self-assisted lobectomies. The median age was 70 years old, predominately female (57%) and white (85%) with 90% of patients undergoing surgery for cancer. The median of estimated blood loss was 25 mL during the operation with no conversions to open thoracotomies. After the operation, 17% of patients had major postoperative complications with a median length of stay of 2 days. At thirty-day follow-up, the readmission rate was 6.5%, with a mortality of 0%. Compared to the propensity matched VATS lobectomy group, there was significantly less conversion to open surgery (n=0, 0% vs. n=10, 12.2%, P=0.002), less intraoperative blood transfusions (n=0, 0% vs. n=6, 7.3%, P=0.03), less any complications (n=20, 24.4% vs. n=41, 50%, P=0.003), and less median length of stay (2 days, IQR 2, 5 days vs. 4 day, IQR 3, 6 days, P<0.001) in the self-assisting robot lobectomy group. Compared to published outcomes of robot-assisted lobectomy, our series had significantly fewer conversions to open (P=0.03), shorter length of stay (P<0.001), more discharges to home (93.7%) without a difference in procedure time (P=0.38), overall complication rates (P=0.16) and mortality (P=0.62). Conclusions: Self-assistance using the robot technology during pulmonary lobectomy had few technical complications and acceptable morbidity, length of stay, and mortality. This group had favorable outcome compared to VATS lobectomy. The ability to self-assist during pulmonary lobectomy is an additional benefit of the robot technology compared to open and VATS lobectomy.
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BACKGROUND: The Lung Cancer Study Group has shown that lobectomy provides the best survival in patients with non-small cell lung cancer. However, as patients become older, lobectomy may not provide a survival advantage compared with sublobar resection. METHODS: We analyzed the National Cancer Database for octogenarians with pathologic stage I lung cancer from 2004 to 2016. We then evaluated the patients who underwent lobectomy or sublobar (segmentectomy or wedge) resection for the treatment of cancer. We analyzed the 5-year survival rates of the groups as well as a cubic spline plot to determine age cutoffs where lobectomy does not provide improved survival. RESULTS: Among the octogenarians (227 134), there were 25 362 (26%) who had pathologic stage I lung cancer. There were 6370 (30%) patients who had sublobar resections (segmentectomy [n = 1192] and wedge resection [n = 5178]), whereas 14 594 (70%) patients had a lobectomy. There was significantly improved survival at 5 years with lobectomy compared with sublobar resection (48.5% vs 41.1%; P < .001). The cubic spline plot provided evidence that there was no age at which sublobar resection provided survival better than or equal to lobectomy (P < .001). CONCLUSIONS: In octogenarians with pathologic stage I lung cancer, lobectomy provided better 5-year survival compared with sublobar resection regardless of the age at surgical procedure. Hence, all patients with stage I cancer should be considered for a lobectomy if they are medically able to tolerate such a procedure.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Idoso de 80 Anos ou mais , Humanos , Neoplasias Pulmonares/patologia , Pneumonectomia/métodos , Estadiamento de Neoplasias , Taxa de Sobrevida , Estudos RetrospectivosRESUMO
BACKGROUND: Porcine liver xenografts represent a potential solution to the organ shortage, but thrombocytopenia occurs within minutes to hours after xenotransplantation, preventing clinical application. Recently, it was discovered that porcine liver sinusoidal endothelial cells (LSEC) bind and phagocytose human platelets. We examined the role of ASGR1 in binding and removing human platelets by the pig liver endothelium. METHODS: Primary porcine enriched LSEC (eLSEC) were characterized by flow cytometry, immunoblot, quantitative PCR, and immunohistochemistry using confocal microscopy. Phagocytosis inhibition assays using anti-ASGR1 and an ASGR1 substrate were performed. ASGR1 was targeted for siRNA knockdown, and ASGR1-reduced cells were tested for human platelet binding and phagocytosis. RESULTS: ASGR1 is expressed by eLSEC. Human platelet binding and phagocytosis by porcine eLSEC was inhibited by asialofetuin, but not fetuin, suggesting an interaction with galactose ß1-4 N-acetyl glucosamine. Anti-ASGR1 antibodies inhibited human platelet binding in a dose-dependent manner. Knockdown experiments using siRNA reduced ASGR1 expression in asynchronous primary eLSEC by 40%-80%. There was a 20% reduction in translated protein significantly correlated with a 21% decrease in human platelet binding. CONCLUSIONS: ASGR1 on porcine eLSEC mediates phagocytosis of xenogeneic platelets.