RESUMO
One of the major hurdles that has hindered the success of chimeric antigen receptor (CAR) T cell therapies against solid tumors is on-target off-tumor (OTOT) toxicity due to sharing of the same epitopes on normal tissues. To elevate the safety profile of CAR-T cells, an affinity/avidity fine-tuned CAR was designed enabling CAR-T cell activation only in the presence of a highly expressed tumor associated antigen (TAA) but not when recognizing the same antigen at a physiological level on healthy cells. Using direct stochastic optical reconstruction microscopy (dSTORM) which provides single-molecule resolution, and flow cytometry, we identified high carbonic anhydrase IX (CAIX) density on clear cell renal cell carcinoma (ccRCC) patient samples and low-density expression on healthy bile duct tissues. A Tet-On doxycycline-inducible CAIX expressing cell line was established to mimic various CAIX densities, providing coverage from CAIX-high skrc-59 tumor cells to CAIX-low MMNK-1 cholangiocytes. Assessing the killing of CAR-T cells, we demonstrated that low-affinity/high-avidity fine-tuned G9 CAR-T has a wider therapeutic window compared to high-affinity/high-avidity G250 that was used in the first anti-CAIX CAR-T clinical trial but displayed serious OTOT effects. To assess the therapeutic effect of G9 on patient samples, we generated ccRCC patient derived organotypic tumor spheroid (PDOTS) ex vivo cultures and demonstrated that G9 CAR-T cells exhibited superior efficacy, migration and cytokine release in these miniature tumors. Moreover, in an RCC orthotopic mouse model, G9 CAR-T cells showed enhanced tumor control compared to G250. In summary, G9 has successfully mitigated OTOT side effects and in doing so has made CAIX a druggable immunotherapeutic target.
Assuntos
Anidrases Carbônicas , Carcinoma de Células Renais , Neoplasias Renais , Receptores de Antígenos Quiméricos , Animais , Camundongos , Humanos , Anidrase Carbônica IX/genética , Carcinoma de Células Renais/metabolismo , Neoplasias Renais/patologia , Receptores de Antígenos Quiméricos/genética , Anidrases Carbônicas/metabolismo , Anidrases Carbônicas/uso terapêutico , Antígenos de Neoplasias , Anticorpos , Linfócitos T/metabolismoRESUMO
Esophageal surgery has evolved significantly since the first esophagectomy, with advancements in diagnosis allowing medicine to keep pace with the disease's increasing incidence. Multimodal treatment improves outcomes, but surgical resection remains imperative for local control, with various techniques in existence but none demonstrating clear superiority. More recently, minimally invasive and robotic surgery have further reduced perioperative morbidity. This review discusses techniques for esophageal resection, with attention to the options available for anastomosis and reconstructive conduits.
Assuntos
Neoplasias Esofágicas , Procedimentos Cirúrgicos Robóticos , Humanos , Anastomose Cirúrgica/métodos , Neoplasias Esofágicas/cirurgia , Esofagectomia/métodos , Procedimentos Cirúrgicos Robóticos/métodos , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Resultado do TratamentoRESUMO
BACKGROUND AND OBJECTIVES: Stage IVa thymic malignancy has limited treatments. This study evaluated whether hyperthermic intraoperative chemotherapy (HIOC) after radical resection of Stage IVa thymic malignancy improves survival. METHODS: All patients who underwent resection, with or without HIOC, for Stage IVa thymic malignancy at a single center from 1990 to 2021 were reviewed. RESULTS: Thirty-four patients were identified; 22 surgery-only versus 12 surgery and HIOC (60 min cisplatin regimen 175 mg/m2 ). Demographics and comorbidities were similar between groups. Three patients in each group were carcinomas; remainder were thymomas. Thirty-two patients underwent attempted macroscopic complete resection; 22 operations succeeded, 68.8%. Significant complications were similar between groups, 18.2% surgery-only versus 25.0% HIOC, p = 0.68. Median time to recurrence trended longer for HIOC patients (42.9 vs. 32.9 months in surgery-only, p = 0.77). Overall survival, 5-year, was similar (75.8% HIOC vs. 76.2% surgery-only, p = 0.91). On stratified analysis, thymoma patients with macroscopic complete resection and HIOC experienced similar 5-year Overall (80.0% vs. 100.0% surgery-only, p = 0.157) but longer trending 5-year disease-free (85.7% vs. 40.0%, p = 0.18) and 5-year locoregional recurrence-free survival (85.7% vs. 68.6%, p = 0.75). CONCLUSIONS: This retrospective cohort study treating Stage IVa thymic malignancy with radical pleurectomy, with or without HIOC, found addition of HIOC-signaled delayed recurrence and improved disease-free survival.
Assuntos
Timoma , Neoplasias do Timo , Humanos , Intervalo Livre de Doença , Estudos Retrospectivos , Resultado do Tratamento , Timectomia , Neoplasias do Timo/cirurgia , Neoplasias do Timo/patologia , Timoma/cirurgia , Timoma/patologia , Estadiamento de NeoplasiasRESUMO
We compared clinicopathologic and molecular features of esophageal squamous cell carcinoma (SCC) with basaloid features to conventional SCC using surgical resections of treatment naïve esophageal carcinomas and cases available from the TCGA database. Twenty-two cases of SCC with basaloid features were identified in the Mass General Brigham pathology archives, including 9 cases with pure basaloid morphology and 13 cases with mixed other features such as conventional well- or poorly differentiated areas or sarcomatoid areas. Thirty-eight cases of conventional SCC matched by tumor stage were used as controls. HPV infection status was tested by p16 immunohistochemistry and HPV mRNA ISH. Digital slides for 94 cases of esophageal SCC from TCGA found in the Genomic Data Commons (GDC) Data Portal were reviewed. Five cases of SCC with basaloid features were identified. Genomic profiles of SCC with basaloid features were compared to the rest of 89 SCCs without basaloid features. In addition, eight tumor sections from six patients selected from our cohort underwent in-house molecular profiling. Compared to conventional SCC, SCC with basaloid features were more frequently associated with diffuse or multifocal squamous dysplasia (p < 0.001). P16 IHC was positive in 2/13 cases, whereas HPV mRNA ISH was negative in 17/17 cases (including both p16-positive cases). SCC with basaloid features and conventional SCC from TCGA showed similar rates of TP53 mutations, CDKN2A/B deletions, and CCDN1 amplifications. TP53 variants were identified in all in-house samples that had sufficient coverage. Survival analyses between SCC with basaloid features versus conventional SCC (matched for tumor stage) did not reveal any statistically significant differences. In conclusion, esophageal SCC with basaloid features has similar survival and genomic alterations to those of conventional SCC, are more frequently associated with diffuse or multifocal dysplasia, and are not associated with HPV (high-risk strains) infection.
Assuntos
Carcinoma de Células Escamosas , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Infecções por Papillomavirus , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/genética , Carcinoma de Células Escamosas/patologia , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago/genética , Humanos , RNA MensageiroRESUMO
BACKGROUND: We investigate the incidence and risk factors for post-operative outcomes including chyle leak following minimally invasive esophagectomy (MIE). METHODS: Patients undergoing MIE from May 2016 until August 2020 were prospectively followed. Outcomes of robotic and video-assisted thoracoscopic surgery (VATS) esophagectomy were analyzed. RESULTS: 347 esophagectomies were performed: 70 cases were done robotically by 2 surgeons and 277 by VATS by 14 surgeons. Patients had similar demographics, surgical technique, length of stay (LOS), and re-operation rates. Overall complication rates between robotic and VATS MIE were statistically similar (61% vs. 50%; p = 0.082). The majority of complications for either VATS (41.5%) or robotic-assisted minimally invasive esophagectomy (RAMIE) (51.4%) were grade II. Nineteen patients developed a chyle leak. Patients with a chyle leak were similar in age, gender, and hospital LOS (all p > 0.05), but were more likely to undergo a three-hole or robotic esophagectomy (both p < 0.05) as well as have higher rehabilitation requirements on discharge (26% vs. 10%; p = 0.05). Among the two surgeons who each performed > 20 robotic esophagectomies (n = 70), nine chyle leaks occurred. Rates varied by surgeon (7 vs. 2; p = 0.003). Lower leak rates occurred in the surgeon with more robotic esophagectomy experience (n = 47 vs. 23). Patients were similar in age, and gender (p > 0.05), but those with a chyle leak were more likely to undergo three-hole esophagectomies, prophylactic thoracic duction ligations, undergo the abdominal portion via laparotomy, and not have a prophylactic omental flap (all p < 0.05). CONCLUSION: Robotic and VATS esophagectomy have similar rates of re-operation, length of stay, discharge needs and complications. Differences in outcomes between VATS and Robotic esophagectomy appears to be related to surgeon experience with the robot but may also be associated with techniques such as anastomotic height, omental flap utilization and performance of laparoscopy.
Assuntos
Quilo , Neoplasias Esofágicas , Procedimentos Cirúrgicos Robóticos , Robótica , Neoplasias Esofágicas/complicações , Esofagectomia/efeitos adversos , Esofagectomia/métodos , Humanos , Tempo de Internação , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgia , Estudos Retrospectivos , Procedimentos Cirúrgicos Robóticos/efeitos adversos , Cirurgia Torácica Vídeoassistida/efeitos adversos , Resultado do TratamentoRESUMO
AIMS: Oesophageal verrucous carcinoma (VSCC) is a rare and morphologically distinct type of oesophageal squamous cell carcinoma (SCC). Diagnosing VSCC on biopsy material is challenging, given the lack of significant atypia and the presence of keratinising epithelium and exophytic growth. The molecular pathogenesis of VSCC remains unclear. The aim of this study was to characterise the genomic landscape of VSCC in comparison to conventional oesophageal SCC. METHODS AND RESULTS: Three cases of VSCC from the Brigham and Women's Hospital pathology archive were identified. Formalin-fixed, paraffin-embedded (FFPE) tumour tissue was used for p16 immunohistochemistry (IHC), high-risk human papillomavirus (HPV) in-situ mRNA hybridisation (ISH) and DNA isolation. Tumour DNA was sequenced using a targeted massively parallel sequencing assay enriched for cancer-associated genes. Three additional cases of VSCC were identified by image review of The Cancer Genome Atlas (TCGA) oesophageal SCC cohort. VSCC cases were negative for p16 IHC and high-risk HPV ISH. TP53 mutations (P < 0.001) and copy number variants (CNVs) for CDKN2A (P < 0.001), CDKN2B (P < 0.01) and CCND1 (P < 0.01) were absent in VSCC and significantly less frequent in comparison to conventional SCC. Five VSCC cases featured SMARCA4 missense mutations or in-frame deletions compared to only four of 88 conventional SCC cases (P < 0.001). VSCC featured driver mutations in PIK3CA, HRAS and GNAS. Recurrent CNVs were rare in VSCC. CONCLUSIONS: VSCC is not only morphologically but also genetically distinct from conventional oesophageal SCC, featuring frequent SMARCA4 mutations and infrequent TP53 mutations or CDKN2A/B CNVs. Molecular findings may aid in establishing the challenging diagnosis of VSCC.
Assuntos
Carcinoma Verrucoso/genética , Carcinoma Verrucoso/patologia , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/patologia , Idoso , Carcinoma de Células Escamosas do Esôfago/genética , Carcinoma de Células Escamosas do Esôfago/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND AND OBJECTIVES: The aim of this study was to demonstrate whether academic thoracic surgeons could achieve morbidity and mortality rates in community hospitals equivalent to those seen in National Lung Screening Trial (NLST). METHODS: This was a retrospective review of community hospital lung cancer procedures for clinical Stage I-III non-small-cell lung cancers from 2007 through 2014. Variables include age, comorbidities, computed tomography (CT) characterization, and operative techniques. RESULTS: There were 177 patients who had lung cancers removed by a minimally invasive approach (79%), including lobectomy in 127 (72%), segmentectomy in 4 (2%), and wedge-resections in 46 (26%). The median patient age was 71 years (interquartile range [IQR], 63-76). The cohort was primarily female (58%), clinical Stage I (82%), with a median tumor size of 2.3 cm (IQR, 1.5-3.3). The median length of stay was 6 days (range: 1-35). Complications were experienced by 78 (44.1%) patients, most commonly atrial fibrillation in 20 (11.3%) followed by air-leak in 19 (10.7%). There were no in-hospital deaths. Tumor location and extent of resection were associated with complications, while larger tumor size, margin contour, and resection method were associated with air-leak (all p < 0.05). Higher clinical stage and larger tumor size were associated with occult Stage III disease (both p < 0.05). CONCLUSIONS: The low morbidity and mortality rates from the NLST were achievable in a community setting for early-stage lung cancer. Characterization of cancers using CT imaging identified factors most commonly associated with postoperative complications and the presence of occult Stage III disease.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/cirurgia , Complicações Pós-Operatórias/epidemiologia , Idoso , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Feminino , Hospitais Comunitários , Humanos , Tempo de Internação , Neoplasias Pulmonares/diagnóstico , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Pneumonectomia , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do TratamentoRESUMO
BACKGROUND: The purpose of this study was to evaluate treatment strategies and factors influencing overall survival (OS) and disease-free survival (DFS) in resectable, non-small cell lung cancer (NSCLC) with mediastinal (N2) lymph node metastasis. METHODS: All patients undergoing surgery for NSCLC with N2 disease between 2006 and 2016 were included. Treatment approaches included surgery only, neoadjuvant therapy followed by surgery, surgery followed by adjuvant therapy, and neoadjuvant therapy followed by surgery and adjuvant therapy (triple therapy). Patient clinical and pathologic data were retrospectively collected. RESULTS: A total of 281 patients were included in the study. In total, 209 patients had neoadjuvant therapy, 47.4% of which went on to received additional adjuvant therapy. The pathologic complete response rate was 12.9%. The treatment strategy which included triple therapy was isolated as a significant contributor to improved OS and DFS. Nodal downstaging (N0) after induction therapy conferred an OS benefit (38.3% vs. 15.6%, p = .03). Patients with single-station N2 disease experienced higher DFS. Video-assisted thoracic surgery (VATS) lobectomy completion rates were higher at the end of the study period compared to the beginning (p < .001). CONCLUSIONS: Patients who undergo neoadjuvant therapy for N2-positive NSCLC may benefit from additional adjuvant therapy. Single-station N2 disease confers higher DFS. VATS completion rates for lobectomy increase as experience increases.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/mortalidade , Quimioterapia de Indução/mortalidade , Neoplasias Pulmonares/mortalidade , Terapia Neoadjuvante/mortalidade , Recidiva Local de Neoplasia/mortalidade , Pneumonectomia/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/terapia , Terapia Combinada , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/terapia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/terapia , Estadiamento de Neoplasias , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
INTRODUCTION: Postoperative delirium is a common complication after major surgical procedures and affects outcomes and long-term survival. We identified factors associated with postoperative delirium in patients undergoing esophagectomy. METHODS: Retrospective cohort analysis of 378 patients undergoing esophagectomy. We examined the association between postoperative delirium (DSM-V) criteria with respect to baseline variables and postoperative complications. RESULTS: Postoperative delirium was diagnosed in 64 (16.93%) patients and associated with increasing age (P < .05), chronic obstructive pulmonary disease (P = .07), pneumonia (P = .01), transfusion intraoperatively or within 72 hours of surgery (P < .001), and sepsis (P = .001). Unplanned intubation and increased length of stay (median, 14 days) were significant in patients with delirium (P = .001 and P < .001, respectively). In a secondary analysis, surgical technique and operative approach were associated with delirium. Modified McKeown (three-hole) esophagectomy was twice more likely to develop delirium compared with Ivor Lewis (odds ratio [OR], 2.09; 95% confidence interval [CI], 1.03-4.23). The strongest association was found between delirium and open techniques (thoracotomy and laparotomy) as compared with minimally invasive techniques (thoracoscopy and laparoscopy) (OR, 2.66; 95% CI, 1.22-5.76). Survival was similar between both groups. CONCLUSIONS: Postoperative delirium is common and associated with complications following esophagectomy. Identification of predisposing factors such as age and pre-existing pulmonary diseases and proper selection of surgical treatment may reduce delirium and improve surgical outcomes.
Assuntos
Delírio/etiologia , Esofagectomia/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Delírio/epidemiologia , Neoplasias Esofágicas/epidemiologia , Neoplasias Esofágicas/cirurgia , Esofagectomia/estatística & dados numéricos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Fatores de Risco , Adulto JovemRESUMO
PURPOSE: To facilitate localization and resection of small lung nodules, we developed a prospective clinical trial (ClinicalTrials.gov number NCT01847209) for a novel surgical approach which combines placement of fiducials using intra-operative C-arm computed tomography (CT) guidance with standard thoracoscopic resection technique using image-guided video-assisted thoracoscopic surgery (iVATS). METHODS: Pretrial training was performed in a porcine model using C-arm CT and needle guidance software. Methodology and workflow for iVATS was developed, and a multi-modality team was trained. A prospective phase I-II clinical trial was initiated with the goal of recruiting eligible patients with small peripheral pulmonary nodules. Intra-operative C-arm CT scan was utilized for guidance of percutaneous marking with two T-bars (Kimberly-Clark, Roswell, GA) followed by VATS resection of the tumor. RESULTS: Twenty-five patients were enrolled; 23 underwent iVATS, one withdrew, and one lesion resolved. Size of lesions were: 0.6-1.8 cm, mean = 1.3 ± 0.38 cm.. All 23 patients underwent complete resection of their lesions. CT imaging of the resected specimens confirmed the removal of the T-bars and the nodule. Average and total procedure radiation dose was in the acceptable low range (median = 1501 µGy*m(2), range 665-16,326). There were no deaths, and all patients were discharged from the hospital (median length of stay = 4 days, range 2-12). Three patients had postoperative complications: one prolonged air-leak, one pneumonia, and one ileus. CONCLUSIONS: A successful and safe step-wise process has been established for iVATS, combining intra-operative C-arm CT scanning and thoracoscopic surgery in a hybrid operating room.
Assuntos
Neoplasias Pulmonares/cirurgia , Nódulos Pulmonares Múltiplos/cirurgia , Complicações Pós-Operatórias , Nódulo Pulmonar Solitário/cirurgia , Cirurgia Assistida por Computador/métodos , Cirurgia Torácica Vídeoassistida/métodos , Tomografia Computadorizada por Raios X/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Cuidados Intraoperatórios , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Nódulos Pulmonares Múltiplos/diagnóstico por imagem , Nódulos Pulmonares Múltiplos/patologia , Estadiamento de Neoplasias , Pneumonectomia , Prognóstico , Estudos Prospectivos , Radiografia Intervencionista , Nódulo Pulmonar Solitário/diagnóstico por imagem , Nódulo Pulmonar Solitário/patologia , Adulto JovemRESUMO
McKeown esophagectomy is a transthoracic esophagectomy with a cervical anastomosis that is an established mainstay for the management of benign and malignant esophageal pathology. It has gone through multiple modifications. The most current version utilizes robotic or minimally invasive ports through both the right chest and abdominal portions. There is decreased pain and hospital length of stay compared to the open technique. However, anastomotic leak and recurrent laryngeal nerve injury continue to occur. Advancements in management of complications has decreased mortality, making this surgical approach a relevant option for esophageal pathologies.
Assuntos
Neoplasias Esofágicas , Esofagectomia , Procedimentos Cirúrgicos Minimamente Invasivos , Humanos , Esofagectomia/métodos , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Neoplasias Esofágicas/cirurgia , Procedimentos Cirúrgicos Robóticos/métodosRESUMO
Immune suppression within tumor microenvironments (TME) have been implicated in limited efficacy of immune check point inhibitors (ICIs) against solid tumors. Down-regulated VentX expression in tumor associated macrophages (TAMs) underlies phagocytotic anergic phenotype of TAMs, which govern immunological state of TME. In this study, using a tumor immune microenvironment enabling model system (TIME-EMS) of non-small cell lung cancer (NSCLC), we found that PD-1 antibody modestly activates cytotoxic T lymphocytes (CTLs) within the NSCLC-TME but not the status of TIME. We showed that the restoration of VentX expression in TAMs reignites the phagocytotic function of TAMs, which in turn, transforms TIME, activates CTLs in a tumor-specific manner and promotes efficacy of PD-1 antibody against NSCLC but not toxicity on normal lung epithelial cells. Supported by in vivo data on NSG-PDX models of primary human NSCLC, our study revealed potential venues to promote the efficacy of ICI against solid tumors through VentX-based mechanisms.
RESUMO
Background: The esophagectomy surgical Apgar score (eSAS) has been found to be a predictor of postoperative complications in esophagectomy. In our previous study, we built a graphic nomogram based on eSAS and demonstrated that it can effectively predict the risk of major morbidity after esophagectomy. In this study, we aimed to assess the benefits of using an eSAS-based nomogram model as a postoperative risk-based triage system for patients undergoing esophagectomy. Methods: We enrolled 119 patients diagnosed with esophageal carcinoma and randomly assigned them to a nomogram group (NG) or control group (CG) from January 2019 to December 2020. Patients in the NG were assigned to a low-risk group and high-risk group based on the nomogram. Patients in the high-risk group were admitted to the intensive care unit (ICU) after esophagectomy. Risk estimation in the CG patients was based on the surgeon's clinical experience. Thirty-day major complications, postoperative hospital stay, hospital costs, and quality of life (QOL) during the follow-up were compared between the two groups. Results: Baseline clinicopathological characteristics were comparable between the NG (n=58) and CG (n=61). All patients underwent esophagectomy. Postoperative complications were significantly higher in the CG (30, 49.2%) than in the NG (14, 24.1%) (P=0.008), with pneumonia being the most common (CG: 23, 37.7%; NG: 12, 20.7%; P=0.042). There was no significant difference in anastomotic leakage (NG: 1, 1.7%; CG: 6, 9.8%; P=0.12). Postoperative median hospital stay was shorter in the NG (14 days) than in the CG (16 days) (P=0.041). Hospital costs (NG: ¥60,045.1; CG: ¥63,961.5; P=0.21) and postoperative QOL did not differ significantly between groups. Conclusions: An eSAS-based nomogram as a triage system can reduce the overall occurrence of postoperative complications and shorten postoperative hospital stay without increasing hospital costs. Trial Registration: Chinese Clinical Trial Registry ChiCTR1900021636.
RESUMO
Background: Reported advantages to robotic thoracic surgery include shorter length of stay (LOS), improved lymphadenectomy, and decreased complications. It is uncertain if these benefits occur when introducing robotics into a well-established video-assisted thoracoscopy (VATS) practice. We compared the two approaches to investigate these advantages. Materials and methods: IRB approval was obtained for this project. Patients who underwent segmentectomy or lobectomy from May 2016-December 2018 were propensity-matched 2: 1 (VATS: robotic) and compared using weighted logistic regression with age, gender, Charlson Comorbidity Index, surgery type, stage, Exparel, and epidural as covariates. Complication rates, operation times, number of sampled lymph nodes, pain level, disposition, and LOS were compared using Wilcoxon rank-sum and with Rao-Scott Chi-squared tests. Results: 213 patients (142 VATS and 71 robot) were matched. Duration of robotic cases was longer than VATS (median 186 min (IQR 78) vs. 164 min (IQR 78.75); p < 0.001). Significantly more lymph nodes (median 11 (IQR 7.50) vs. 8 (IQR 7.00); p = 0.004) and stations were sampled (median 4 (IQR 2.00) vs. 3 (IQR 1.00); p < 0.001) with the robot. Interestingly, robotic resections had higher 72-hour pain scores (median 3 (IQR 3.25) vs. 2 (IQR 3.50); p = 0.04) and 48-hour opioid usage (median 37.50 morphine milligram equivalents (MME) (IQR 45.50) vs. 22.50 MME (IQR 37.50); p = 0.01). Morbidity, LOS, and disposition were similar (all p > 0.05). Conclusions: The robotic approach facilitates better lymph node sampling, even in an established VATS practice.
RESUMO
Objective: The impact of conduit dimensions and location of esophagogastric anastomosis on long-term quality of life after esophagectomy remains unexplored. We investigated the association of these parameters with surgical outcomes and patient-reported quality of life at least 18 months after esophagectomy. Methods: We identified all patients who underwent esophagectomy for cancer from 2018 to 2020 in our institution. We reviewed each patient's initial postoperative computed tomography scan measuring the gastric conduit's greatest width (centimeters), linear staple line length (centimeters), and relative location of esophagogastric anastomosis (vertebra). Quality of life was ascertained using patient-reported outcome measures. Perioperative complications, length of stay, and mortality were collected. Multivariate regressions were performed. Results: Our study revealed that a more proximal anastomosis was linked to an increased risk of pulmonary complications, a lower recurrence rate, and greater long-term insomnia. Increased maximum intrathoracic conduit width was significantly associated with trouble enjoying meals and reflux long term after esophagectomy. A longer conduit stapled line correlated with fewer issues related to insomnia, improved appetite, less dysphagia, and significantly enhanced "social," "role," and "physical'" aspects of the patient's long-term quality of life. Conclusions: The dimensions of the gastric conduit and the height of the anastomosis may be independently associated with outcomes and long-term quality of life after esophagectomy for cancer.
RESUMO
The role of Human papillomavirus (HPV) infection in esophageal squamous cell carcinoma (ESCC) is a topic of ongoing debate. This study used two screening approaches to look for evidence of HPV infection in esophageal squamous cell carcinoma. We initially checked for HPV infection in a randomly selected group of 53 ESCC cases. We did not detect any tumors positive for high-risk HPV. However, during clinical practice, we identified an HPV-positive ESCC in the distal esophagus, which tested positive for HPV16. This index case was TP53 wild-type, as determined by next-generation DNA sequencing (NGS). Since TP53 mutations are rare in other HPV-driven cancers, we improved our screening method by limiting our screen to a subset of ESCC cases without TP53 mutations. A second screen of 95 ESCCs (from 93 patients) sequenced by NGS revealed an additional 7 ESCCs with TP53 wild-type status (7.3% of the total). Of the 7 cases, 2 cases were found to be high-risk HPV positive. Both patients also tested positive for circulating cell-free HPV DNA and had a complete response to neoadjuvant chemoradiation. The index patient had microscopic residual tumor following neoadjuvant therapy. The patient underwent adjuvant immunotherapy and remained disease free after 22 months of surveillance. This study affirms the transcriptionally active status of high-risk HPV in a minority of ESCC patients in North America.
Assuntos
Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Infecções por Papillomavirus , Proteína Supressora de Tumor p53 , Humanos , Infecções por Papillomavirus/virologia , Infecções por Papillomavirus/terapia , Infecções por Papillomavirus/complicações , Neoplasias Esofágicas/virologia , Neoplasias Esofágicas/terapia , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago/virologia , Carcinoma de Células Escamosas do Esôfago/genética , Carcinoma de Células Escamosas do Esôfago/terapia , Carcinoma de Células Escamosas do Esôfago/patologia , Masculino , Feminino , Pessoa de Meia-Idade , Proteína Supressora de Tumor p53/genética , Idoso , DNA Viral/genética , América do Norte/epidemiologia , Transcrição Gênica , Papillomavirus Humano 16/genética , Papillomavirus Humano 16/isolamento & purificação , Sequenciamento de Nucleotídeos em Larga Escala , Resultado do Tratamento , Mutação , Quimiorradioterapia Adjuvante , Terapia Neoadjuvante , Biomarcadores Tumorais/genética , Testes de DNA para Papilomavírus HumanoRESUMO
INTRODUCTION: Gastroesophageal reflux has been associated with poorer lung transplantation outcomes, although no standard approach to evaluation/management has been adopted. We aimed to evaluate the effect of timely antireflux treatment as guided by routine reflux testing on postlung transplant rejection outcomes. METHODS: This was a retrospective cohort study of lung transplant recipients at a tertiary center. All patients underwent pretransplant ambulatory pH monitoring. Timely antireflux treatment was defined as proton pump inhibitor initiation or antireflux surgery within 6 months of transplantation. Patients were separated into 3 groups: normal pH monitoring (-pH), increased reflux (+pH) with timely treatment, and +pH with delayed treatment. Rejection outcomes included acute rejection, bronchiolitis obliterans syndrome, and chronic lung allograft dysfunction per International Society for Heart and Lung Transplantation criteria. Time-to-event analyses using Cox proportional hazard models were applied. Patients not meeting outcomes were censored at death or last clinic visit. RESULTS: One hundred seventy-five patients (59% men/mean 56.3 yr/follow-up: 496 person-years) were included. On multivariable analyses, +pH/delayed treatment patients had higher risks of acute rejection (adjust hazard ratio [aHR]:3.81 [95% confidence interval [CI]: 1.90-7.64], P = 0.0002), bronchiolitis obliterans syndrome (aHR: 2.22 [95% CI: 1.07-4.58], P = 0.03), and chronic lung allograft dysfunction (aHR: 2.97 [95% CI: 1.40-6.32], P = 0.005) than +pH/timely treatment patients. Similarly, rejection risks were increased among +pH/delayed treatment patients vs -pH patients (all P < 0.05). No significant differences in rejection risks were noted between +pH/timely treatment patients and -pH patients. Failure/complications of antireflux treatment were rare and similar among groups. DISCUSSION: Timely antireflux treatment, as directed by pretransplant reflux testing, was associated with reduced allograft rejection risks and demonstrated noninferiority to patients without reflux. A standardized peri-transplant test-and-treat algorithm may guide timely reflux management to improve lung transplant outcomes.
Assuntos
Refluxo Gastroesofágico , Transplante de Pulmão , Masculino , Humanos , Feminino , Estudos Retrospectivos , Refluxo Gastroesofágico/diagnóstico , Refluxo Gastroesofágico/tratamento farmacológico , Refluxo Gastroesofágico/complicações , Transplante de Pulmão/efeitos adversos , Pulmão , Monitoramento do pH EsofágicoRESUMO
OBJECTIVE: The advent of lung cancer screening and detection of smaller nodules amplifies the need to clarify the oncological quality of sublobar resections. Furthermore, studies comparing sublobar resections to lobectomies offer conflicting conclusions. We hypothesize that this is driven, in part, by inconsistency in reporting; that is, variable interpretation of what constitutes an operative segment. Without an established standard, 2 very different operations may be reported as segmental resections, leaving the data on sublobar approaches subject to interpretative variability. METHODS: A retrospective audit was performed on all segmental resections from May 2016 to December 2019 at Brigham and Women's Hospital. Pathology and operative reports were reviewed, with particular attention to the dissection of the component artery, vein, and bronchus. Resections with dissection and division of at least 1 major vascular structure (the segmental artery or vein), as well as the segmental bronchus, met operative criteria for anatomic segmentectomy. Surgical quality metrics were compared between the 2 groups. RESULTS: There were 271 segmental resections: 219 (80.8%) were anatomic segmentectomies and 52 (19.2%) were nonanatomic segmentectomies. For the entire cohort, nonanatomic segmentectomies had smaller margins (1.0 vs 1.5 cm; P = .02), fewer lymph nodes (2.0 vs 6.0; P < .001), and fewer mediastinal lymph node stations sampled (1.0 vs 2.0; P < .001). Similarly, there were smaller margins (1.5 vs 1.8 cm; P = .03), fewer lymph nodes (2.0 vs 6.0; P < .001), and fewer mediastinal lymph node stations sampled (1.0 vs 2.0; P < .001) in nonanatomic segmentectomies for non-small cell lung cancer. CONCLUSIONS: Nearly 20% of reported segmentectomies may not meet criteria for true segmental resection. Therefore, prior studies may need further scrutiny to clarify outcomes and results. Establishing a professional standard may help mitigate ambiguity in published data on this subject.