Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 39
Filter
1.
JCI Insight ; 9(13)2024 May 23.
Article in English | MEDLINE | ID: mdl-38781019

ABSTRACT

Immunosuppression is a common feature of esophageal adenocarcinoma (EAC) and has been linked to poor overall survival (OS). We hypothesized that upstream factors might negatively influence CD3 levels and T cell activity, thus promoting immunosuppression and worse survival. We used clinical data and patient samples of those who progressed from Barrett's to dysplasia to EAC, investigated gene (RNA-Seq) and protein (tissue microarray) expression, and performed cell biology studies to delineate a pathway impacting CD3 protein stability that might influence EAC outcome. We showed that the loss of both CD3-ε expression and CD3+ T cell number correlated with worse OS in EAC. The gene related to anergy in lymphocytes isoform 1 (GRAIL1), which is the prominent isoform in EACs, degraded (ε, γ, δ) CD3s and inactivated T cells. In contrast, isoform 2 (GRAIL2), which is reduced in EACs, stabilized CD3s. Further, GRAIL1-mediated CD3 degradation was facilitated by interferon-stimulated gene 15 (ISG15), a ubiquitin-like protein. Consequently, the overexpression of a ligase-dead GRAIL1, ISG15 knockdown, or the overexpression of a conjugation-defective ISG15-leucine-arginine-glycine-glycine mutant could increase CD3 levels. Together, we identified an ISG15/GRAIL1/mutant p53 amplification loop negatively influencing CD3 levels and T cell activity, thus promoting immunosuppression in EAC.


Subject(s)
Adenocarcinoma , CD3 Complex , Cytokines , Esophageal Neoplasms , Ubiquitins , Humans , Esophageal Neoplasms/genetics , Esophageal Neoplasms/mortality , Esophageal Neoplasms/pathology , Esophageal Neoplasms/metabolism , Esophageal Neoplasms/immunology , Adenocarcinoma/genetics , Adenocarcinoma/mortality , Adenocarcinoma/pathology , Adenocarcinoma/metabolism , Adenocarcinoma/immunology , CD3 Complex/metabolism , CD3 Complex/genetics , Cytokines/metabolism , Ubiquitins/metabolism , Ubiquitins/genetics , Male , T-Lymphocytes/metabolism , T-Lymphocytes/immunology , Female , Gene Expression Regulation, Neoplastic , Barrett Esophagus/pathology , Barrett Esophagus/genetics , Barrett Esophagus/metabolism , Middle Aged
2.
Cell Death Dis ; 15(3): 194, 2024 Mar 08.
Article in English | MEDLINE | ID: mdl-38453895

ABSTRACT

The advancement of RNAseq and isoform-specific expression platforms has led to the understanding that isoform changes can alter molecular signaling to promote tumorigenesis. An active area in cancer research is uncovering the roles of ubiquitination on spliceosome assembly contributing to transcript diversity and expression of alternative isoforms. However, the effects of isoform changes on functionality of ubiquitination machineries (E1, E2, E3, E4, and deubiquitinating (DUB) enzymes) influencing onco- and tumor suppressor protein stabilities is currently understudied. Characterizing these changes could be instrumental in improving cancer outcomes via the identification of novel biomarkers and targetable signaling pathways. In this review, we focus on highlighting reported examples of direct, protein-coded isoform variation of ubiquitination enzymes influencing cancer development and progression in gastrointestinal (GI) malignancies. We have used a semi-automated system for identifying relevant literature and applied established systems for isoform categorization and functional classification to help structure literature findings. The results are a comprehensive snapshot of known isoform changes that are significant to GI cancers, and a framework for readers to use to address isoform variation in their own research. One of the key findings is the potential influence that isoforms of the ubiquitination machinery have on oncoprotein stability.


Subject(s)
Gastrointestinal Neoplasms , Humans , Ubiquitination , Protein Isoforms/genetics , Protein Isoforms/metabolism , Gastrointestinal Neoplasms/genetics , Carcinogenesis , Tumor Suppressor Proteins/metabolism , Ubiquitin-Protein Ligases/metabolism
3.
J Thorac Cardiovasc Surg ; 167(4): 1469-1478.e3, 2024 Apr.
Article in English | MEDLINE | ID: mdl-37625618

ABSTRACT

OBJECTIVE: Our statewide thoracic quality collaborative has implemented multiple quality improvement initiatives to improve lung cancer nodal staging. We subsequently implemented a value-based reimbursement initiative to further incentivize quality improvement. We compare the impact of these programs to steer future quality improvement initiatives. METHODS: Since 2016, our collaborative focused on improving lymph node staging for lung cancer by leveraging unblinded, hospital-level metrics and collaborative feedback. In 2021, a value-based reimbursement initiative was implemented with statewide yearly benchmark rates for (1) preoperative mediastinal staging for ≥T2N0 lung cancer, and (2) sampling ≥5 lymph node stations. Participating surgeons would receive additional reimbursement if either benchmark was met. We reviewed patients from January 2015 to March 2023 at the 21 participating hospitals to determine the differential effects on quality improvement. RESULTS: We analyzed 6228 patients. In 2015, 212 (39%) patients had ≥5 nodal stations sampled, and 99 (51%) patients had appropriate preoperative mediastinal staging. During 2016 to 2020, this increased to 2253 (62%) patients and 739 (56%) patients, respectively. After 2020, 1602 (77%) patients had ≥5 nodal stations sampled, and 403 (73%) patients had appropriate preoperative mediastinal staging. Interrupted time-series analysis demonstrated significant increases in adequate nodal sampling and mediastinal staging before value-based reimbursement. Afterward, preoperative mediastinal staging rates briefly dropped but significantly increased while nodal sampling did not change. CONCLUSIONS: Collaborative quality improvement made significant progress before value-based reimbursement, which reinforces the effectiveness of leveraging unblinded data to a collaborative group of thoracic surgeons. Value-based reimbursement may still play a role within a quality collaborative to maintain infrastructure and incentivize participation.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Humans , Lung Neoplasms/surgery , Lung Neoplasms/pathology , Carcinoma, Non-Small-Cell Lung/pathology , Quality Improvement , Lymph Nodes/surgery , Lymph Nodes/pathology , Mediastinum/pathology , Neoplasm Staging
4.
Heliyon ; 9(12): e23212, 2023 Dec.
Article in English | MEDLINE | ID: mdl-38144324

ABSTRACT

Background: Neoadjuvant chemoradiation with esophagectomy is standard management for locally advanced esophageal cancer. Studies have shown that surgical timing following chemoradiation is important for minimizing postoperative complications, however in practice timing is often variable and delayed. Although postoperative impact of surgical timing has been studied, less is known about factors associated with delays. Materials and methods: A retrospective review was performed for 96 patients with esophageal cancer who underwent chemoradiation then esophagectomy between 2018 and 2020 at a single institution. Univariable and stepwise multivariable analyses were used to assess association between social (demographics, insurance) and clinical variables (pre-operative weight, comorbidities, prior cardiothoracic surgery, smoking history, disease staging) with time to surgery (≤8 weeks "on-time" vs. >8 weeks "delayed"). Results: Fifty-one patients underwent esophagectomy within 8 weeks of chemoradiation; 45 had a delayed operation. Univariate analysis showed the following characteristics were significantly different between on-time and delayed groups: weight loss within 3 months of surgery (3.9 ± 5.1 kg vs. 1.5 ± 3.6 kg; P = 0.009), prior cardiovascular disease (29% vs. 49%; P = 0.05), prior cardiothoracic surgery (4% vs. 22%; P = 0.01), history of ever smoked (69% vs. 87%; P = 0.04), absent nodal metastasis on pathology (57% vs. 82%; P = 0.008). Multivariate analysis demonstrated that prior cardiothoracic surgery (OR 8.924, 95%CI 1.67-47.60; P = 0.01) and absent nodal metastasis (OR 4.186, 95%CI 1.50-11.72; P = 0.006) were associated with delayed surgery. Conclusions: Delayed esophagectomy following chemoradiotherapy is associated with prior cardiothoracic surgery and absent nodal metastasis. Further investigations should focus on understanding how these factors contribute to delays to guide treatment planning and mitigate sources of outcome disparities.

5.
Ann Thorac Surg ; 116(6): 1168-1175, 2023 12.
Article in English | MEDLINE | ID: mdl-37704003

ABSTRACT

BACKGROUND: Despite advances in operative techniques and postoperative care, esophagectomy remains a morbid operation. Leveraging complication epidemiology and the correlation of these complications may improve rescue and refine early recovery pathways. METHODS: This study retrospectively reviewed all esophagectomies performed at a tertiary academic center from 2014 to 2021 and quantified the timing of the most common complications. Daily incidence values for index complications were calculated, and a covariance matrix was created to examine the correlation of the complications with each other. Study investigators performed a Cox proportional hazards analysis to clarify the association between early diagnosis of postoperative atrial fibrillation and pneumonia with subsequent anastomotic leak. RESULTS: The study analyzed 621 esophagectomies, with 580 (93.4%) cervical anastomoses and 474 (76%) patients experiencing complications. A total of 159 (25.6%) patients had postoperative atrial fibrillation, and 155 (25.0%) had an anastomotic leak. The median (interquartile range [IQR]) postoperative day of these complications was day 2 (IQR, days 2-3) and day 8 (IQR, days 7-11), respectively. Our covariance matrix found significant associations in the variance of the most common postoperative complications, including pneumonia, atrial fibrillation, anastomotic leak, and readmissions. Early postoperative atrial fibrillation (hazard ratio, 8.1; 95% CI, 5.65-11.65) and postoperative pneumonia (hazard ratio, 3.8; 95% CI, 1.98-7.38) were associated with anastomotic leak. CONCLUSIONS: Maintaining a high index of suspicion for early postoperative complications is crucial for rescuing patients after esophagectomy. Early postoperative pneumonia and atrial fibrillation may be sentinel complications for an anastomotic leak, and their occurrence may be used to prompt further clinical investigation. Early recovery protocols should consider the development of early complications into postoperative feeding and imaging algorithms.


Subject(s)
Atrial Fibrillation , Esophageal Neoplasms , Pneumonia , Humans , Anastomotic Leak/epidemiology , Anastomotic Leak/etiology , Anastomotic Leak/surgery , Esophagectomy/adverse effects , Esophagectomy/methods , Retrospective Studies , Atrial Fibrillation/epidemiology , Atrial Fibrillation/etiology , Atrial Fibrillation/surgery , Esophageal Neoplasms/complications , Postoperative Complications/etiology , Pneumonia/epidemiology , Pneumonia/etiology
7.
J Thorac Dis ; 15(6): 3285-3294, 2023 Jun 30.
Article in English | MEDLINE | ID: mdl-37426143

ABSTRACT

Background: Opioid prescribing guidelines have significantly decreased overprescribing and post-discharge use after cardiac surgery; however, limited recommendations exist for general thoracic surgery patients, a similarly high-risk population. We examined opioid prescribing and patient-reported use to develop evidence-based, opioid prescribing guidelines after lung cancer resection. Methods: This prospective, statewide, quality improvement study was conducted between January 2020 to March 2021 and included patients undergoing surgical resection of a primary lung cancer across 11 institutions. Patient-reported outcomes at 1-month follow-up were linked with clinical data and Society of Thoracic Surgery (STS) database records to characterize prescribing patterns and post-discharge use. The primary outcome was quantity of opioid used after discharge; secondary outcomes included quantity of opioid prescribed at discharge and patient-reported pain scores. Opioid quantities are reported in number of 5-mg oxycodone tablets (mean ± standard deviation). Results: Of the 602 patients identified, 429 met inclusion criteria. Questionnaire response rate was 65.0%. At discharge, 83.4% of patients were provided a prescription for opioids of mean size 20.5±13.1 pills, while patients reported using 8.2±13.0 pills after discharge (P<0.001), including 43.7% who used none. Those not taking opioids on the calendar day prior to discharge (32.4%) used fewer pills (4.4±8.1 vs. 11.7±14.9, P<0.001). Refill rate was 21.5% for patients provided a prescription at discharge, while 12.5% of patients not prescribed opioids at discharge required a new prescription before follow-up. Pain scores were 2.4±2.5 for incision site and 3.0±2.8 for overall pain (scale 0-10). Conclusions: Patient-reported post-discharge opioid use, surgical approach, and in-hospital opioid use before discharge should be used to inform prescribing recommendations after lung resection.

8.
Surg Endosc ; 37(9): 6989-6997, 2023 09.
Article in English | MEDLINE | ID: mdl-37349594

ABSTRACT

BACKGROUND: Gastric ischemic preconditioning prior to esophagectomy has been studied as a method to improve gastric conduit perfusion and reduce anastomotic complications, without conclusive results. The aim of this study is to evaluate the feasibility and safety of gastric ischemic preconditioning in terms of post-operative outcomes and quantitative gastric conduit perfusion. METHODS: Patients who underwent an esophagectomy with gastric conduit reconstruction between January 2015 and October 2022 at a single high-volume academic center were reviewed. Patient characteristics, surgical approach, post-operative outcomes, and indocyanine green fluorescence angiography data (ingress index for arterial inflow and ingress time for venous outflow, and the distance from the last gastroepiploic branch to the perfusion assessment point) were analyzed. Two propensity score weighting methods were used to investigate whether gastric ischemic preconditioning reduces anastomotic leaks. Multiple linear regression analysis was used to evaluate the conduit perfusion quantitatively. RESULTS: There were 594 esophagectomies with gastric conduit performed, with 41 having a gastric ischemic preconditioning. Among 544 with cervical anastomoses, leaks were seen in 2/30 (6.7%) in the ischemic preconditioning group and 114/514 (22.2%) in the control group (p = 0.041). Gastric ischemic preconditioning significantly reduced anastomotic leaks on both weighting methods (p = 0.037 and 0.047, respectively). Ingress index and time of the gastric conduit with ischemic preconditioning were significantly better than those without preconditioning (p = 0.013 and 0.025, respectively) after removing the effect of the distance from the last gastroepiploic branch to the perfusion assessment point. CONCLUSION: Gastric ischemic preconditioning results in a statistically significant improvement in conduit perfusion and reduction in post-operative anastomotic leaks.


Subject(s)
Esophageal Neoplasms , Ischemic Preconditioning , Humans , Esophagectomy/methods , Anastomotic Leak/etiology , Anastomotic Leak/prevention & control , Anastomotic Leak/surgery , Propensity Score , Stomach/surgery , Anastomosis, Surgical/methods , Perfusion , Ischemic Preconditioning/methods , Esophageal Neoplasms/surgery , Esophageal Neoplasms/complications
9.
Am J Clin Pathol ; 160(3): 322-330, 2023 09 01.
Article in English | MEDLINE | ID: mdl-37256702

ABSTRACT

OBJECTIVES: To report histologic features of unsuspected diffuse pleural mesothelioma (DPM) in surgical specimens for pneumothorax and demonstrate how ancillary markers support a diagnosis of malignancy in this context. We explored whether pneumothorax may be a clinical manifestation of mesothelioma in situ (MIS). METHODS: A single-institution database search identified patients who underwent surgical resection for spontaneous pneumothorax (n = 229) and/or were diagnosed with DPM (n = 88) from 2000 to 2020. RESULTS: Spontaneous pneumothorax without clinical, radiologic, or intraoperative suspicion of mesothelioma was the initial presentation in 2 (2.3%) of 88 patients diagnosed with DPM. This represented 0.9% (2/229) of all patients undergoing surgical management of pneumothorax but accounted for a larger proportion of older patients (12.5% older than 70 years). Immunohistochemistry for BAP-1 and/or MTAP confirmed the diagnosis of DPM in 2 cases. Mesothelioma in situ was identified retrospectively by immunohistochemistry in 1 case of spontaneous pneumothorax from a 77-year-old man who developed invasive DPM 25 months later. No additional cases of MIS were identified in 19 surgical lung resections for spontaneous pneumothorax. CONCLUSIONS: Histologic examination of bleb resections with ancillary testing for cases with ambiguous features is essential for detection of early DPM. It is uncertain whether spontaneous pneumothorax may represent a clinical manifestation of MIS.


Subject(s)
Mesothelioma, Malignant , Mesothelioma , Pleural Neoplasms , Pneumothorax , Male , Humans , Aged , Pneumothorax/diagnosis , Pneumothorax/surgery , Retrospective Studies , Mesothelioma/complications , Mesothelioma/diagnosis , Mesothelioma/surgery , Pleural Neoplasms/complications , Pleural Neoplasms/diagnosis
10.
J Surg Res ; 289: 241-246, 2023 09.
Article in English | MEDLINE | ID: mdl-37150078

ABSTRACT

INTRODUCTION: We defined institutional opioid prescribing patterns, established prescribing guidelines, and evaluated the adherence to and effectiveness of these guidelines in association with opioid prescribing after hiatal hernia repair (HHR). METHODS: A retrospective chart review was completed for patients who underwent transthoracic (open) or laparoscopic HHR between January and December 2016. Patient-reported opioid use after surgery was used to establish prescribing recommendations. Guideline efficacy was then evaluated among patients undergoing HHR after implementation (August 2018 to June 2019). Data are reported in oral morphine equivalents (OMEs). RESULTS: The initial cohort included n = 87 patients (35 open; 52 laparoscopic) with a 68% survey response rate. For open repair, median prescription size was 338 mg OME (interquartile range [IQR] 250-420) with patient-reported use of 215 mg OME (IQR 78-308) (P = 0.002). Similarly, median prescription size was 270 mg OME (IQR 200-319) with patient-reported use of 100 mg OME (IQR 4-239) (P < 0.001) for laparoscopic repair. Opioid prescribing guidelines were defined as the 66th percentile of patient-reported opioid use. Postguideline implementation cohort included n = 108 patients (36 open; 72 laparoscopic). Median prescription amount decreased by 54% for open and 43% laparoscopic repair, with no detectable change in the overall refill rate after guideline implementation. Patient education, opioid storage, and disposal practices were also characterized. CONCLUSIONS: Evidence-based opioid prescribing guidelines can be successfully implemented for open and laparoscopic HHR with a high rate of compliance and without an associated increase in opioid refills.


Subject(s)
Analgesics, Opioid , Opioid-Related Disorders , Humans , Analgesics, Opioid/therapeutic use , Retrospective Studies , Herniorrhaphy/adverse effects , Pain, Postoperative/drug therapy , Pain, Postoperative/etiology , Practice Patterns, Physicians'
11.
Ann Thorac Surg ; 115(5): 1238-1245, 2023 05.
Article in English | MEDLINE | ID: mdl-36240869

ABSTRACT

BACKGROUND: The role of operative approach in surgical lymphadenectomies and pathologic nodal upstaging for lung cancer remains unclear. METHODS: This study retrospectively reviewed patients who underwent lobectomy for non-small cell lung cancer from January 2015 to December 2020 at 16 centers within a statewide quality improvement collaborative in Michigan. Patients were stratified by operative approach, and our primary end points were number of LN recovered, number of LN stations sampled, and rates of nodal upstaging with nodal upstaging defined as a higher final pathologic nodal stage compared with preoperative clinical nodal staging. RESULTS: A total of 3036 patients were included: 608 (20.0%) with open lobectomies, 1362 (41.3%) with video-assisted thoracoscopic surgery (VATS), and 1233 (37.4%) with robot-assisted thoracoscopic surgery (RATS) lobectomies. Using multivariable logistic regression, study investigators found that VATS was associated with lower rates of nodal upstaging (odds ratio [OR], 0.71; 95% CI, 0.54-0.94; P = .015) and harvesting ≥10 LNs (OR, 0.40; 95% CI, 0.31-0.50; P < .001) as compared with open surgery, whereas no significant difference was found between RATS and open techniques. Compared with open surgery, VATS had lower rates of sampling at ≥5 nodal stations (OR, 0.66; 95% CI, 0.53-0.84; P = .001), whereas RATS rates were higher (OR, 2.38; 95% CI, 1.85-3.06; P < .001). CONCLUSIONS: VATS lobectomies were associated with lower rates of harvesting ≥10 LNs, sampling ≥5 LN stations, and pathologic nodal upstaging compared with open and RATS lobectomies. Compared with open procedures, RATS lobectomies were associated with higher rates of sampling ≥5 LN stations, but there was no significant difference between open and RATS approaches in rates of nodal upstaging or harvesting ≥10 LNs.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Humans , Lung Neoplasms/surgery , Lung Neoplasms/pathology , Carcinoma, Non-Small-Cell Lung/surgery , Carcinoma, Non-Small-Cell Lung/pathology , Retrospective Studies , Pneumonectomy/methods , Neoplasm Staging , Thoracic Surgery, Video-Assisted/methods , Lymph Node Excision , Lymph Nodes/pathology
12.
J Gastrointest Surg ; 27(5): 845-854, 2023 05.
Article in English | MEDLINE | ID: mdl-36526829

ABSTRACT

BACKGROUND: It remains unclear what is the ideal conduit shape. The aim of this study was to evaluate association between specific gastric conduit morphology, considering width and length, with its perfusion and the incidence of anastomotic leaks after esophagectomy. METHODS: Patients who underwent an esophagectomy with cervical esophagogastric anastomosis between 2015 and 2021 were evaluated. Indocyanine green angiography was performed to evaluate gastric conduit perfusion, and ingress index (arterial inflow) and ingress time (venous outflow) were measured. The conduit width at the middle of the conduit and the short gastric length as the length from the last gastroepiploic branch to the perfusion assessment point were measured. Propensity score matching was performed to compare wide conduits with narrow conduits. Narrow and wide conduits were defined as < 4 and ≥ 5 cm, respectively. RESULTS: Three hundred fifty-eight patients were reviewed. After applying matching, the wide conduits had higher ingress index (48.2 vs 33.3%, p < 0.001) and shorter ingress time (51.2 vs 66.3 s, p = 0.004) compared to the narrow conduits. Including the short gastric length in analysis, creating a wide conduit is a significant factor for better ingress index (p = 0.001), especially when the perfusion assessment point is 5 cm or farther from the last gastroepiploic branch. Anastomotic leaks did not differ between the groups. CONCLUSIONS: Conduit width is a significant factor of gastric conduit perfusion, especially when the estimated anastomotic site was > 5 cm from the last gastroepiploic branch. Wide conduits seem to have better perfusion and creating a wider conduit might reduce anastomotic leaks.


Subject(s)
Anastomotic Leak , Esophagectomy , Humans , Anastomosis, Surgical/adverse effects , Anastomotic Leak/etiology , Anastomotic Leak/surgery , Angiography , Esophageal Neoplasms/surgery , Esophagectomy/adverse effects , Stomach/blood supply
13.
J Thorac Cardiovasc Surg ; 166(1): 241-250.e3, 2023 07.
Article in English | MEDLINE | ID: mdl-36456358

ABSTRACT

OBJECTIVES: In January 2016, our statewide quality improvement collaborative focused on 3 metrics of adequate lymph node harvest during lung cancer surgery: (1) rates of pathologic examination of 10 lymph nodes or more; (2) sampling 5 or more lymph node stations or more within the hilum or mediastinum; and (3) pathologic nodal upstaging (pathologic nodal stage higher than clinical nodal stage). Unblinded, hospital-level outcomes were presented at biannual meetings, and opportunities for education or improvement were discussed. We set out to describe this quality improvement initiative and the subsequent impact on surgical lymphadenectomies statewide. METHODS: We retrospectively reviewed patients undergoing lobectomy for stage IA to IIIA non-small-cell lung cancer from July 2015 to December 2020 at the 16 participating centers. RESULTS: The study cohort included 3753 patients. The rates of examining 10 lymph nodes or more statewide increased from 215 lobectomies (44.0%) in 2015 to 522 lobectomies (78.9%) in 2020 (P < .001). Similar trends were noted statewide for 5 lymph node stations or more, which increased from 193 lobectomies (39.6%) to 531 lobectomies (80.3%) in 2020 (P < .001). The overall rate of nodal upstaging was more variable year to year and generally declined over time (P = .004). CONCLUSIONS: Our statewide quality improvement initiative improved rates of appropriate lymph node staging for surgically treated non-small cell lung cancer compared with national rates. This work demonstrates the power that a "community of practice" philosophy can have on surgical treatment of lung cancer. Quality improvement interventions including transparent data-driven discussions and collaboration can help guide future quality improvement initiatives and should be readily transferrable to other clinical domains.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Humans , Carcinoma, Non-Small-Cell Lung/surgery , Carcinoma, Non-Small-Cell Lung/pathology , Lung Neoplasms/surgery , Lung Neoplasms/pathology , Retrospective Studies , Quality Improvement , Treatment Outcome , Neoplasm Staging , Pneumonectomy/adverse effects , Lymph Node Excision , Lymph Nodes/surgery , Lymph Nodes/pathology
14.
Mol Ther Nucleic Acids ; 29: 749-768, 2022 Sep 13.
Article in English | MEDLINE | ID: mdl-36090744

ABSTRACT

Isoform switching events with predicted functional consequences are common in many cancers, but characterization of switching events in esophageal adenocarcinoma (EAC) is lacking. Next-generation sequencing was used to detect levels of RNA transcripts and identify specific isoforms in treatment-naïve esophageal tissues ranging from premalignant Barrett's esophagus (BE), BE with low- or high-grade dysplasia (BE.LGD, BE.HGD), and EAC. Samples were stratified by histopathology and TP53 mutation status, identifying significant isoform switching events with predicted functional consequences. Comparing BE.LGD with BE.HGD, a histopathology linked to cancer progression, isoform switching events were identified in 75 genes including KRAS, RNF128, and WRAP53. Stratification based on TP53 status increased the number of significant isoform switches to 135, suggesting switching events affect cellular functions based on TP53 mutation and tissue histopathology. Analysis of isoforms agnostic, exclusive, and shared with mutant TP53 revealed unique signatures including demethylation, lipid and retinoic acid metabolism, and glucuronidation, respectively. Nearly half of isoform switching events were identified without significant gene-level expression changes. Importantly, two TP53-interacting isoforms, RNF128 and WRAP53, were significantly linked to patient survival. Thus, analysis of isoform switching events may provide new insight for the identification of prognostic markers and inform new potential therapeutic targets for EAC.

15.
Radiographics ; 42(4): 1012-1027, 2022.
Article in English | MEDLINE | ID: mdl-35522576

ABSTRACT

Tracheobronchomalacia (TBM) and excessive dynamic airway collapse (EDAC) are airway abnormalities that share a common feature of expiratory narrowing but are distinct pathophysiologic entities. Both entities are collectively referred to as expiratory central airway collapse (ECAC). The malacia or weakness of cartilage that supports the tracheobronchial tree may occur only in the trachea (ie, tracheomalacia), in both the trachea and bronchi (TBM), or only in the bronchi (bronchomalacia). On the other hand, EDAC refers to excessive anterior bowing of the posterior membrane into the airway lumen with intact cartilage. Clinical diagnosis is often confounded by comorbidities including asthma, chronic obstructive pulmonary disease, obesity, hypoventilation syndrome, and gastroesophageal reflux disease. Additional challenges include the underrecognition of ECAC at imaging; the interchangeable use of the terms TBM and EDAC in the literature, which leads to confusion; and the lack of clear guidelines for diagnosis and treatment. The use of CT is growing for evaluation of the morphology of the airway, tracheobronchial collapsibility, and extrinsic disease processes that can narrow the trachea. MRI is an alternative tool, although it is not as widely available and is not used as frequently for this indication as is CT. Together, these tools not only enable diagnosis, but also provide a road map to clinicians and surgeons for planning treatment. In addition, CT datasets can be used for 3D printing of personalized medical devices such as stents and splints. An invited commentary by Brixey is available online. Online supplemental material is available for this article. ©RSNA, 2022.


Subject(s)
Tracheobronchomalacia , Bronchi/diagnostic imaging , Humans , Stents , Trachea/diagnostic imaging , Tracheobronchomalacia/diagnostic imaging , Tracheobronchomalacia/surgery
16.
Ann Thorac Surg ; 113(5): 1591-1597, 2022 05.
Article in English | MEDLINE | ID: mdl-32599037

ABSTRACT

BACKGROUND: Robotic-assisted thoracic surgery (RATS) lung lobectomy has emerged as an alternative approach to video-assisted thoracoscopic surgery (VATS). Patient-reported outcomes comparing these approaches have been limited. METHODS: At a single, high-volume academic center, patients undergoing VATS and RATS lobectomies for stage I and II non-small cell lung cancer from 2014 to 2018 were evaluated. The European Organisation for Research and Treatment of Cancer Quality of Life of Cancer Patients Questionnaire (QLQ-C30) and Quality of Life Questionnaire in Lung Cancer (QLQ-LC13), along with the Fear of Recurrence (FoR) survey, were administered preoperatively and at 1, 6, and 12 months postoperatively. Raw scores underwent linear transformation (0-100 scale). Linear mixed-effects models were used for quality of life and FoR score comparisons. RESULTS: The study included 219 patients (139 VATS and 80 RATS). RATS patients had longer (P < .05) operative times and a higher incidence (P < .05) of postoperative myocardial infarction compared to VATS patients. VATS patients reported higher (P < .05) QLQ-C30 summary scores postoperatively and at 12 months, including higher (P < .05) Social Functioning and Cognitive scores, and less (P < .05) appetite loss. VATS patients reported decreased (P < .05) QLQ-LC13 symptom summary scores at 6 months postoperatively, including decreased (P < .05) dyspnea, neuropathy, and pain compared with RATS patients. VATS patients also reported lower (P < .05) FoR summary scores at 6 months postoperatively. CONCLUSIONS: VATS patients report improvement in select quality of life and FoR measures after lobectomy. Further study comparing these 2 approaches is required.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Robotic Surgical Procedures , Benchmarking , Carcinoma, Non-Small-Cell Lung/etiology , Carcinoma, Non-Small-Cell Lung/surgery , Humans , Lung , Lung Neoplasms/etiology , Lung Neoplasms/surgery , Pneumonectomy/adverse effects , Quality of Life , Thoracic Surgery, Video-Assisted/adverse effects
17.
Ann Thorac Surg ; 113(2): 399-405, 2022 02.
Article in English | MEDLINE | ID: mdl-33745901

ABSTRACT

BACKGROUND: Patient-reported outcomes (PROs) for minimally invasive esophagectomy (MIE) have demonstrated benefits compared with open transthoracic or 3-hole esophagectomy. PROs, including quality of life (QoL) and fear of recurrence (FoR), comparing open transhiatal esophagectomy (THE) and transhiatal robotic-assisted MIE (Th-RAMIE) have been limited. METHODS: At a single, high-volume academic center, patients undergoing THE and Th-RAMIE with gastric conduit for clinical stage I to III esophageal cancer from 2013 to 2018 were evaluated. The European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30), the EORTC Quality of Life Questionnaire in Esophageal Cancer (QLQ-OES18), and the FoR survey were administered preoperatively and at 1, 6, and 12 months postoperatively. Linear mixed-effects models were used for QoL and FoR score comparisons. Perioperative outcomes were also compared. RESULTS: A total of 309 patients (212 in the group and 97 in the Th-RAMIE group) were included. The Th-RAMIE cohort had a significantly higher number of lymph nodes harvested (14 ± 0.8 vs 11.2 ± 0.4; P = .01), a shorter length of stay (days, 10.0 ± 6.7 vs 12.1 ± 7.0; P = .03), lower rates of postoperative ileus (5% vs 15%; P = .02), and fewer opioids prescribed at discharge (71% vs 85%; P = .03). After adjustment, there were no significant differences in QLQ-C30, QLQ-OES18, and FoR scores between the groups out to 1 year postoperatively. CONCLUSIONS: There were no clear patient-reported benefits of Th-RAMIE over THE for esophageal cancer. However, Th-RAMIE conferred several perioperative benefits.


Subject(s)
Adenocarcinoma/surgery , Esophageal Neoplasms/surgery , Esophagectomy/methods , Laparotomy/methods , Quality of Life , Robotic Surgical Procedures/methods , Adenocarcinoma/diagnosis , Adolescent , Adult , Aged , Aged, 80 and over , Esophageal Neoplasms/diagnosis , Follow-Up Studies , Humans , Middle Aged , Neoplasm Staging , Propensity Score , Prospective Studies , Time Factors , Treatment Outcome , Young Adult
18.
J Robot Surg ; 16(4): 883-891, 2022 Aug.
Article in English | MEDLINE | ID: mdl-34581956

ABSTRACT

Esophagectomy is a high-risk operation, regardless of technique. Minimally invasive transthoracic esophagectomy could reduce length of stay and pulmonary complications compared to traditional open approaches, but the benefits of minimally invasive transhiatal esophagectomy are unclear. We performed a retrospective review of prospectively gathered data for open transhiatal esophagectomies (THEs) and transhiatal robot-assisted minimally invasive esophagectomies (TH-RAMIEs) performed at a high-volume academic center between 2013 and 2017. Multivariate logistic regression was used to calculate adjusted odds ratios (aORs) for outcomes. 465 patients met inclusion criteria (378 THE and 87 TH-RAMIE). THE patients more likely had an ASA score of 3 + (89.1% vs 77.0%, p = 0.012), whereas TH-RAMIE patients more likely had a pathologic staging of 3+ (43.7% vs. 31.2%, p = 0.026). TH-RAMIE patients were less likely to receive epidurals (aOR 0.06, 95% confidence interval [CI] 0.03-0.14, p < 0.001), but epidural use itself was not associated with differences in outcomes. TH-RAMIE patients experienced higher rates of pulmonary complications (adjusted odds ratio [OR] 1.82, 95% CI 1.03-3.22, p = 0.040), particularly pulmonary embolus (aOR 5.20, 95% CI 1.30-20.82, p = 0.020). There were no statistically significant differences in lymph node harvest, unexpected ICU admission, length of stay, in-hospital mortality, or 30-day readmission or mortality rates. The TH-RAMIE approach had higher rates of pulmonary complications. There were no statistically significant advantages to the TH-RAMIE approach. Further investigation is needed to understand the benefits of a minimally invasive approach to the open transhiatal esophagectomy.


Subject(s)
Esophageal Neoplasms , Robotic Surgical Procedures , Robotics , Esophageal Neoplasms/pathology , Esophageal Neoplasms/surgery , Esophagectomy/methods , Humans , Lymph Nodes/surgery , Minimally Invasive Surgical Procedures/methods , Postoperative Complications/etiology , Robotic Surgical Procedures/methods , Treatment Outcome
19.
Dis Esophagus ; 35(5)2022 May 10.
Article in English | MEDLINE | ID: mdl-34913060

ABSTRACT

Impaired gastric conduit perfusion is a risk factor for anastomotic leak after esophagectomy. The aim of this study is to evaluate the feasibility of intraoperative quantitative assessment of gastric conduit perfusion with indocyanine green fluorescence angiography as a predictor for cervical esophagogastric anastomotic leak after esophagectomy. Indocyanine green fluorescence angiography using the SPY Elite system was performed in patients undergoing a transhiatal or McKeown esophagectomy from July 2015 through December 2020. Ingress (dye uptake) and Egress (dye exit) at two anatomic landmarks (the tip of a conduit and 5 cm from the tip) were assessed. The collected data in the leak group and no leak group were compared by univariate and multivariable analyses. Of 304 patients who were evaluated, 70 patients developed anastomotic leak (23.0%). There was no significant difference in patients' demographic between the groups. Ingress Index, which represents a proportion of blood inflow, at both the tip and 5 cm of the conduit was significantly lower in the leak group (17.9 vs. 25.4% [P = 0.011] and 35.9 vs. 44.6% [P = 0.019], respectively). Ingress Time, which represents an estimated time of blood inflow, at 5 cm of the conduit was significantly higher in the leak group (69.9 vs. 57.1 seconds, P = 0.006). Multivariable analysis suggested that these three variables can be used to predict future leak. Variables of gastric conduit perfusion correlated with the incidence of cervical esophagogastric anastomotic leak. Intraoperative measurement of gastric conduit perfusion can be predictive for anastomotic leak following esophagectomy.


Subject(s)
Esophageal Neoplasms , Esophagectomy , Anastomosis, Surgical/adverse effects , Anastomotic Leak/diagnosis , Anastomotic Leak/etiology , Anastomotic Leak/surgery , Esophageal Neoplasms/complications , Esophageal Neoplasms/surgery , Esophagectomy/adverse effects , Humans , Indocyanine Green , Perfusion/adverse effects , Stomach/surgery
20.
Ann Thorac Surg ; 114(6): 2195-2201, 2022 12.
Article in English | MEDLINE | ID: mdl-34924190

ABSTRACT

BACKGROUND: Whether all patients will require an opioid prescription after cardiac surgery is unknown. We performed a multicenter analysis to identify patient predictors of not receiving an opioid prescription at the time of discharge home after cardiac surgery. METHODS: Opioid-naïve patients undergoing coronary artery bypass grafting and/or valve surgery through a sternotomy at 10 centers from January to December 2019 were identified retrospectively from a prospectively maintained data set. Opioid-naïve was defined as not taking opioids at the time of admission. The primary outcome was discharge without an opioid prescription. Mixed-effects logistic regression was performed to identify predictors of discharge without an opioid prescription, and postdischarge opioid prescribing was monitored to assess patient tolerance of discharge without an opioid prescription. RESULTS: Among 1924 eligible opioid-naïve patients, mean age was 64 ± 11 years, and 25% were women. In total, 28% of all patients were discharged without an opioid prescription. On multivariable analysis, older age, longer length of hospital stay, and undergoing surgery during the last 3 months of the study were independent predictors of discharge without an opioid prescription, whereas depression, non-Black and non-White race, and using more opioid pills on the day before discharge were independent predictors of receiving an opioid prescription. Among patients discharged without an opioid prescription, 1.8% (10 of 547) were subsequently prescribed an opioid. CONCLUSIONS: Discharging select patients without an opioid prescription after cardiac surgery appears well tolerated, with a low incidence of postdischarge opioid prescriptions. Increasing the number of patients discharged without an opioid prescription may be an area for quality improvement.


Subject(s)
Analgesics, Opioid , Cardiac Surgical Procedures , Humans , Female , Middle Aged , Aged , Male , Analgesics, Opioid/therapeutic use , Analgesics, Opioid/adverse effects , Patient Discharge , Pain, Postoperative/drug therapy , Pain, Postoperative/etiology , Retrospective Studies , Aftercare , Practice Patterns, Physicians' , Cardiac Surgical Procedures/adverse effects
SELECTION OF CITATIONS
SEARCH DETAIL
...