Publications by authors named "Wayne L Hofstetter"

269 Publications

Robotic Surgery and Anatomic Segmentectomy: An Analysis of Trends, Patient Selection, and Outcomes.

Authors:
Nicolas Zhou Erin M Corsini Mara B Antonoff Wayne L Hofstetter Reza J Mehran Ravi Rajaram Jack A Roth Boris Sepesi Stephen G Swisher Ara A Vaporciyan Garrett L Walsh David C Rice

Ann Thorac Surg 2021 Apr 7. Epub 2021 Apr 7.

Department of Thoracic and Cardiovascular Surgery, University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, Texas, USA 77030. Electronic address:

Background: It is unclear whetherrobotic segmentectomies are advantageous. We describe our experience with the robot, comparing patient populations and outcomes with videoscopic thoracic surgery (VATS) and open resection.

Methods: Patients who received anatomic segmentectomy from 2004-2019 were reviewed. Resection methods were categorized as robotic, VATS, or open. Segmentectomies were categorized as simple or complex. Baseline characteristics and perioperative outcomes were analyzed from 2015-2019 due to implementation of ERAS protocol.

Results: Since 2004, there has been an increase in segmentectomies, including robotic and complex segmentectomies. There were 222 segmentectomies from 2015-2019, of which 77(35%) were robotic, 40(18%) VATS, and 105(47%) open. Complex segmentectomies were higher in the robotic group compared to VATS and open (45% vs. 15% vs. 22%; p<0.001), operative time for robotic resections were also longer compared to VATS and open (205 vs. 147 vs. 147 minutes; p<0.001), but had lower blood loss (50 vs. 75 vs. 100 ml; p<0.001), shorter chest tube days (2 vs. 2 vs. 3 days; p=0.004) and length of stay (3 vs. 3 vs. 4 days; p<0.001). Perioperative mortality was low in all groups. No robotic segmentectomy converted to open compared to 7.5% for VATS (p=0.038). Prolonged air leak was lower for robotic compared to open (4% vs. 13%; p=0.038).

Conclusions: Robotic segmentectomy has increased in our institution, with concurrent rise in atypical segmentectomies. Despite performing more complex procedures, there were no conversions, and low perioperative morbidity and mortality. Our results suggest that the robotic platform can facilitate performance of complex anatomic segmentectomies.
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http://dx.doi.org/10.1016/j.athoracsur.2021.03.068DOI Listing
April 2021

Impact of Psychiatric Comorbidities on Surgical Outcomes for Non-Small Cell Lung Cancer.

Authors:
Jacqueline K Olive Nicolas Zhou Kyle G Mitchell Erin M Corsini Wayne L Hofstetter Reza J Mehran David C Rice Boris Sepesi Stephen G Swisher Ara A Vaporciyan Garrett L Walsh Mara B Antonoff

Ann Thorac Surg 2021 Mar 24. Epub 2021 Mar 24.

Department of Thoracic and Cardiovascular Surgery, University of Texas MD Anderson Cancer Center, Houston, TX. Electronic address:

Background: Psychiatric comorbidities (PC) have been associated with poor surgical outcomes in several malignancies. However, the impact of PC on surgical outcomes for non-small cell lung cancer (NSCLC) remains largely unknown.

Methods: NSCLC patients who underwent pulmonary resection at a single institution between 2006-2017 were included. Presence of preoperative PC was identified by documented diagnostic codes. Demographic, histopathologic, perioperative, and survival data were analyzed. Categorical variables were compared using chi-squared or Fisher's exact test. Overall and disease-free survival were analyzed using Kaplan-Meier method. Univariable and multivariable logistic regression analyses were performed for 30-day readmission.

Results: Among 2907 patients, PC were present preoperatively in 180 (6%), including 130 (72%) anxiety, 52 (29%) depression, 28 (16%) adjustment disorder, 16 (9%) alcohol abuse, 8 (4%) sleep disorder, and 3 (2%) schizophrenia. Patients with PC were younger, with fewer cardiovascular complications. There were no differences in length of stay. However, PC led to increased 30-day readmission (12% vs 6%, p=0.004). Reasons for readmission did not differ between groups (p=0.679). Upon multivariable analysis, PC independently predicted 30-day readmission (OR: 2.00, p=0.005). Importantly, there were no differences in 30- or 90-day mortality (p=0.495 and 0.748, respectively), overall survival (p=0.439), or disease-free survival (p=0.924).

Conclusions: NSCLC patients with and without PC experienced similar perioperative and long-term outcomes, suggesting that individuals should not be denied surgical care on the basis of such comorbidities. However, further research should seek to identify reasons for increased risk of readmission for patients with PC and validate these findings in other settings.
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http://dx.doi.org/10.1016/j.athoracsur.2021.03.034DOI Listing
March 2021

Simultaneous versus staged resections for bilateral pulmonary metastases.

Authors:
Hope A Feldman Nicolas Zhou Mara B Antonoff Wayne L Hofstetter Ravi Rajaram David C Rice Boris Sepesi Ara A Vaporciyan Andres Zorrilla-Vaca Reza J Mehran

J Surg Oncol 2021 Mar 8. Epub 2021 Mar 8.

Department of Thoracic and Cardiovascular Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.

Background: For patients with bilateral pulmonary metastases, staged resections have historically been the preferred surgical intervention. During the spring of 2020, the COVID-19 pandemic made patient travel to the hospital challenging and necessitated reduction in operative volume so that resources could be conserved. We report our experience with synchronous bilateral metastasectomies for the treatment of disease in both lungs.

Methods: Patients with bilateral pulmonary metastases who underwent simultaneous bilateral resections were compared with a cohort of patients who underwent staged resections. We used nearest-neighbor propensity score (1:1) matching to adjust for confounders. Perioperative outcomes were compared between groups using paired statistical analysis techniques.

Results: Between 1998 and 2020, 36 patients underwent bilateral simultaneous metastasectomies. We matched 31 pairs of patients. The length of stay was significantly shorter in patients undergoing simultaneous resection (median 3 vs. 8 days, p < .001) and operative time was shorter (156 vs. 235.5 min, p < .001) when compared to the sum of both procedures in the staged group. The groups did not significantly differ with regard to postoperative complications.

Conclusion: In a carefully selected patient population, simultaneous bilateral metastasectomy is a safe option. A single procedure confers benefits for both the patient as well as the hospital resource system.
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http://dx.doi.org/10.1002/jso.26392DOI Listing
March 2021

Identification of distinct immune landscapes using an automated nine-color multiplex immunofluorescence staining panel and image analysis in paraffin tumor tissues.

Authors:
Edwin R Parra Jie Zhai Auriole Tamegnon Nicolas Zhou Renganayaki Krishna Pandurengan Carmelia Barreto Mei Jiang David C Rice Caitlin Creasy Ara A Vaporciyan Wayne L Hofstetter Anne S Tsao Ignacio I Wistuba Boris Sepesi Cara Haymaker

Sci Rep 2021 Feb 25;11(1):4530. Epub 2021 Feb 25.

Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Unit 9512130 Holcombe Blvd, Houston, TX, 77030, USA.

Immune profiling is becoming a vital tool for identifying predictive and prognostic markers for translational studies. The study of the tumor microenvironment (TME) in paraffin tumor tissues such as malignant pleural mesothelioma (MPM) could yield insights to actionable targets to improve patient outcome. Here, we optimized and tested a new immune-profiling method to characterize immune cell phenotypes in paraffin tissues and explore the co-localization and spatial distribution between the immune cells within the TME and the stromal or tumor compartments. Tonsil tissues and tissue microarray (TMA) were used to optimize an automated nine-color multiplex immunofluorescence (mIF) panel to study the TME using eight antibodies: PD-L1, PD-1, CD3, CD8, Foxp3, CD68, KI67, and pancytokeratin. To explore the potential role of the cells into the TME with this mIF panel we applied this panel in twelve MPM cases to assess the multiple cell phenotypes obtained from the image analysis and well as their spatial distribution in this cohort. We successful optimized and applied an automated nine-color mIF panel to explore a small set of MPM cases. Image analysis showed a high degree of cell phenotype diversity with immunosuppression patterns in the TME of the MPM cases. Mapping the geographic cell phenotype distribution in the TME, we were able to identify two distinct, complex immune landscapes characterized by specific patterns of cellular distribution as well as cell phenotype interactions with malignant cells. Successful we showed the optimization and reproducibility of our mIF panel and their incorporation for comprehensive TME immune profiling into translational studies that could refine our ability to correlate immunologic phenotypes with specific patterns of cells distribution and distance analysis. Overall, this will improve our ability to understand the behavior of cells within the TME and predict new treatment strategies to improve patient outcome.
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http://dx.doi.org/10.1038/s41598-021-83858-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7907283PMC
February 2021

Neoadjuvant nivolumab or nivolumab plus ipilimumab in operable non-small cell lung cancer: the phase 2 randomized NEOSTAR trial.

Authors:
Tina Cascone William N William Annikka Weissferdt Cheuk H Leung Heather Y Lin Apar Pataer Myrna C B Godoy Brett W Carter Lorenzo Federico Alexandre Reuben Md Abdul Wadud Khan Hitoshi Dejima Alejandro Francisco-Cruz Edwin R Parra Luisa M Solis Junya Fujimoto Hai T Tran Neda Kalhor Frank V Fossella Frank E Mott Anne S Tsao George Blumenschein Xiuning Le Jianjun Zhang Ferdinandos Skoulidis Jonathan M Kurie Mehmet Altan Charles Lu Bonnie S Glisson Lauren Averett Byers Yasir Y Elamin Reza J Mehran David C Rice Garrett L Walsh Wayne L Hofstetter Jack A Roth Mara B Antonoff Humam Kadara Cara Haymaker Chantale Bernatchez Nadim J Ajami Robert R Jenq Padmanee Sharma James P Allison Andrew Futreal Jennifer A Wargo Ignacio I Wistuba Stephen G Swisher J Jack Lee Don L Gibbons Ara A Vaporciyan John V Heymach Boris Sepesi

Nat Med 2021 03 18;27(3):504-514. Epub 2021 Feb 18.

Thoracic and Cardiovascular Surgery, University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Ipilimumab improves clinical outcomes when combined with nivolumab in metastatic non-small cell lung cancer (NSCLC), but its efficacy and impact on the immune microenvironment in operable NSCLC remain unclear. We report the results of the phase 2 randomized NEOSTAR trial (NCT03158129) of neoadjuvant nivolumab or nivolumab + ipilimumab followed by surgery in 44 patients with operable NSCLC, using major pathologic response (MPR) as the primary endpoint. The MPR rate for each treatment arm was tested against historical controls of neoadjuvant chemotherapy. The nivolumab + ipilimumab arm met the prespecified primary endpoint threshold of 6 MPRs in 21 patients, achieving a 38% MPR rate (8/21). We observed a 22% MPR rate (5/23) in the nivolumab arm. In 37 patients resected on trial, nivolumab and nivolumab + ipilimumab produced MPR rates of 24% (5/21) and 50% (8/16), respectively. Compared with nivolumab, nivolumab + ipilimumab resulted in higher pathologic complete response rates (10% versus 38%), less viable tumor (median 50% versus 9%), and greater frequencies of effector, tissue-resident memory and effector memory T cells. Increased abundance of gut Ruminococcus and Akkermansia spp. was associated with MPR to dual therapy. Our data indicate that neoadjuvant nivolumab + ipilimumab-based therapy enhances pathologic responses, tumor immune infiltrates and immunologic memory, and merits further investigation in operable NSCLC.
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http://dx.doi.org/10.1038/s41591-020-01224-2DOI Listing
March 2021

Intestinal Metaplasia in the Esophageal Remnant Is Rare After Ivor Lewis Esophagectomy.

Authors:
Erin M Corsini Kyle G Mitchell Nicolas Zhou Mara B Antonoff Reza J Mehran Ravi Rajaram David C Rice Jack A Roth Boris Sepesi Stephen G Swisher Ara A Vaporciyan Garrett L Walsh Wayne L Hofstetter

J Gastrointest Surg 2021 Feb 8. Epub 2021 Feb 8.

Department of Thoracic and Cardiovascular Surgery, University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, Texas, 77030, USA.

Background: Most patients undergoing esophagectomy will experience intermittent reflux of gastric and biliary content into the remnant esophagus postoperatively. The incidence of new or recurrent intestinal metaplasia following chemoradiation and surgery has not been well-described. Furthermore, post-resection guidelines do not exist regarding surveillance for metaplasia in the esophageal remnant.

Methods: Patients undergoing Ivor Lewis esophagectomy after concurrent chemoradiation for a diagnosis of esophageal adenocarcinoma from 2006 to 2018 were identified. Pathology records were reviewed for the presence of intestinal metaplasia on pretreatment biopsies, surgical specimen, or post-resection biopsies.

Results: In total, 619 patients met inclusion criteria, including 267 (43%) who had intestinal metaplasia noted either prior to or at the time of esophagectomy. The median duration of metaplastic disease prior to resection was 4.4 months. During a median follow-up time of 28 months (interquartile range, 12-60), intestinal metaplasia was noted in the remnant esophagus in 12 (2%) patients, 7 of whom had a prior history of metaplasia. Local recurrence of adenocarcinoma was also uncommon, and occurred in 37/577 (6%) of patients with complete resections, with similar event rates among those with and without a prior history of metaplasia (14/249 [6%] vs. 23/328 [7%], p = 0.614).

Conclusions: Our findings suggest that despite several factors predisposing to mucosal damage following esophagectomy, occurrence of new intestinal metaplasia after trimodality therapy in our patient population appears to be rare, even among patient with a previous history of this pathologic finding, which may have significant implications for surveillance and cost-savings after resection.
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http://dx.doi.org/10.1007/s11605-021-04909-2DOI Listing
February 2021

Esophageal Cancer: Tumor-Node-Metastasis Staging.

Authors:
Sonia L Betancourt-Cuellar Marcelo F K Benveniste Diana P Palacio Wayne L Hofstetter

Radiol Clin North Am 2021 Mar;59(2):219-229

Cardiothoracic Department, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 1489, Houston, TX 77030-4009, USA.

Esophageal cancer is an uncommon malignancy that ranks sixth in terms of mortality worldwide. Squamous cell carcinoma is the predominant histologic subtype worldwide whereas adenocarcinoma represents the majority of cases in North America, Australia, and Europe. Esophageal cancer is staged using the American Joint Committee on Cancer and the International Union for Cancer Control TNM system and has separate classifications for the clinical, pathologic, and postneoadjuvant pathologic stage groups. The determination of clinical TNM is based on complementary imaging modalities, including esophagogastroduodenoscopy/endoscopic ultrasound; endoscopic ultrasound-fine-needle aspiration; computed tomography of the chest, abdomen, and pelvis; and fluorodeoxyglucose PET/computed tomography.
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http://dx.doi.org/10.1016/j.rcl.2020.11.008DOI Listing
March 2021

Analysis of Esophagectomy Margin Practice and Survival Implications.

Authors:
Sahar A Saddoughi Kyle Mitchell Mara B Antonoff Kristin M Fruth Jim Taswell Taofic Mounajjed W Wayne L Hofstetter David C Rice K Robert Shen Shanda H Blackmon

Ann Thorac Surg 2021 Jan 29. Epub 2021 Jan 29.

Division of Thoracic Surgery, Department of Surgery, Mayo Clinic, Rochester, MN. Electronic address:

Background: The objective of this study was to determine how thoracic surgeons manage intraoperative esophagectomy positive margins and how these decisions may relate to overall (OS) and progression-free survival (PFS) in esophageal cancer.

Methods: A survey was sent to thoracic surgeons to understand the management of intraoperative positive esophagectomy margins. Primary data at two high volume esophageal cancer institutions from 1994-2017 were retrospectively reviewed to identify patients who had intraoperative positive frozen section margins during esophagectomy. Patient characteristics and survival were collected and analyzed. OS and PFS were assessed using a Cox model.

Results: 85% of thoracic surgeons responding to a survey reported the utilization of frozen pathologic evaluation during esophagectomy with attempts at re-resection to achieve negative margin. Our esophagectomy database identified 94 patients with intraoperative positive margins. Of those re-resected (n=67, 63%), 44 patients (46.8%) were converted to R0 resections. OS was improved for patients in the R0 (13 months) versus R+ groups (3.4 months, p=0.04). PFS was also improved between R0 (8.6 months) versus R+ groups (2.2 months, p=0.03). In a multivariable analysis for PFS, margin status was an independent predictor of survival (HR 3.13, p=0.03).

Conclusions: From a thoracic surgery survey, 85% of surgeons use intraoperative frozen section margin analysis to guide surgical decision-making during an esophagectomy. Analyzing patients with a positive margin discovered during esophagectomy suggests that esophageal cancer patients who can be re-resected to a negative margin have increased PFS. Final margin appears to be related to PFS.
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http://dx.doi.org/10.1016/j.athoracsur.2021.01.028DOI Listing
January 2021

Targeting cancer stem cells with a pan-BCL-2 inhibitor in preclinical and clinical settings in patients with gastroesophageal carcinoma.

Authors:
Shumei Song Qiongrong Chen Yuan Li Guang Lei Ailing Scott Longfei Huo Cordelia Y Li Jeannelyn Santiano Estrella Arlene Correa Melissa Pool Pizzi Lang Ma Jiankang Jin Bin Liu Ying Wang Lianchun Xiao Wayne L Hofstetter Jeffrey H Lee Brian Weston Manoop Bhutani Namita Shanbhag Randy L Johnson Boyi Gan Shaozhong Wei Jaffer A Ajani

Gut 2021 Jan 24. Epub 2021 Jan 24.

Department of GI Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA

Objective: Gastro-oesophageal cancers (GEC) are resistant to therapy and lead to poor prognosis. The cancer stem cells (CSCs) and antiapoptotic pathways often confer therapy resistance. We sought to elucidate the antitumour action of a BCL-2 inhibitor, AT101 in GEC in vitro, in vivo and in a clinical trial.

Methods: Extensive preclinical studies in vitro and in vivo were carried out to establish the mechanism action of AT101 on targeting CSCs and antiapoptotic proteins. A pilot clinical trial in patients with GEC was completed with AT-101 added to standard chemoradiation.

Results: Overexpression of BCL-2 and MCL-1 was noted in gastric cancer tissues (GC). AT-101 induced apoptosis, reduced proliferation and tumour sphere formation in MCL-1/BCL-2 high GC cells. Interestingly, AT101 dramatically downregulated genes () that control CSCs in GEC cell lines regardless of BCL-2/MCL-1 expression. Addition of docetaxel to AT-101 amplified its antiproliferation and induced apoptosis effects. In vivo studies confirmed the combination of AT101 and docetaxel demonstrated stronger antitumour activity accompanied with significant decrease of CSCs biomarkers (YAP1/SOX9). In a pilot clinical trial, 13 patients with oesophageal cancer (EC) received AT101 orally concurrently with chemoradiation. We observed dramatic clinical complete responses and encouraging overall survival in these patients. Clinical specimen analyses revealed that AT-101 dramatically reduced the expression of CSCs genes in treated EC specimens indicating antitumour activity of AT101 relies more on its anti-CSCs activity.

Conclusions: Our preclinical and clinical data suggest that AT-101 overcomes resistance by targeting CSCs pathways suggesting a novel mechanism of action of AT101 in patients with GEC.
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http://dx.doi.org/10.1136/gutjnl-2020-321175DOI Listing
January 2021

Discussion.

Authors:
Wayne L Hofstetter

J Thorac Cardiovasc Surg 2021 Mar 21;161(3):842-843. Epub 2021 Jan 21.

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http://dx.doi.org/10.1016/j.jtcvs.2020.11.107DOI Listing
March 2021

Cancer associated macrophage-like cells and prognosis of esophageal cancer after chemoradiation therapy.

Authors:
Daniel J Gironda Daniel L Adams Jianzhong He Ting Xu Hui Gao Yawei Qiao Ritsuko Komaki James M Reuben Zhongxing Liao Mariela Blum-Murphy Wayne L Hofstetter Cha-Mei Tang Steven H Lin

J Transl Med 2020 11 4;18(1):413. Epub 2020 Nov 4.

Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX, 77030, USA.

Background: Cancer Associated Macrophage-Like cells (CAMLs) are polynucleated circulating stromal cells found in the bloodstream of numerous solid-tumor malignancies. Variations within CAML size have been associated with poorer progression free survival (PFS) and overall survival (OS) in a variety of cancers; however, no study has evaluated their clinical significance in esophageal cancer (EC).

Methods: To examine this significance, we ran a 2 year prospective pilot study consisting of newly diagnosed stage I-III EC patients (n = 32) receiving chemoradiotherapy (CRT). CAML sizes were sequentially monitored prior to CRT (BL), ~ 2 weeks into treatment (T1), and at the first available sample after the completion of CRT (T2).

Results: We found CAMLs in 88% (n = 28/32) of all patient samples throughout the trial, with a sensitivity of 76% (n = 22/29) in pre-treatment screening samples. Improved 2 year PFS and OS was found in patients with CAMLs < 50 μm by the completion of CRT over patients with CAMLs ≥ 50 μm; PFS (HR = 12.0, 95% CI = 2.7-54.1, p = 0.004) and OS (HR = 9.0, 95%CI = 1.9-43.5, p = 0.019).

Conclusions: Tracking CAML sizes throughout CRT as a minimally invasive biomarker may serve as a prognostic tool in mapping EC progression, and further studies are warranted to determine if presence of these cells prior to treatment suggest diagnostic value for at-risk populations.
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http://dx.doi.org/10.1186/s12967-020-02563-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7640696PMC
November 2020

Treatment Patterns for Gastroesophageal Junction Adenocarcinoma in the United States.

Authors:
Bradford J Kim Yi-Ju Chiang Prajnan Das Bruce D Minsky Mariela A Blum Jaffer A Ajani Jeannelyn S Estrella Wayne L Hofstetter Ching-Wei D Tzeng Brian D Badgwell Paul F Mansfield Naruhiko Ikoma

J Clin Med 2020 Oct 29;9(11). Epub 2020 Oct 29.

Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, 1400 Pressler Drive, Unit 1484, Houston, TX 77030, USA.

Despite the increasing incidence of gastroesophageal junction adenocarcinoma (GEJA), the optimal treatment strategy for the disease remains unknown. The objective of this study was to describe treatment patterns for GEJA in the United States. The National Cancer Database was searched to identify all patients who underwent resection of the lower esophagus, abdominal esophagus, and/or gastric cardia for GEJA between 2006 and 2016. Patients were grouped by clinical disease stage: early localized (L; T1-2N0), locally advanced (LA; T3-4N0), regional (R; T1-2N+), or regionally advanced (RA; T3-4N+). The search identified 28,852 GEJA patients. The dominant age range was 60-69 years (39%). Most patients were men (85%), and most were white (92%). Most L patients (69%) underwent upfront surgery, whereas most LA, R, and RA patients received neoadjuvant therapy (NAT; 86%, 80%, and 90%, respectively). Among patients who received NAT, 85% received chemoradiotherapy. Adjuvant therapy was relatively uncommon across all groups (15-20%). In the LA, R, and RA groups, overall survival was greater in patients who received NAT compared to upfront surgery ( < 0.001). With the exception of patients with early localized node-negative disease, most GEJA patients receive neoadjuvant chemoradiotherapy despite the lack of prospective trials reporting survival benefit over chemotherapy alone.
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http://dx.doi.org/10.3390/jcm9113495DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7692279PMC
October 2020

Liposomal Bupivacaine Intercostal Block is Important for Reduction of Pulmonary Complications.

Authors:
Erin M Corsini Kyle G Mitchell Nicolas Zhou Mara B Antonoff Reza J Mehran Gabriel E Mena Ravi Rajaram Jack A Roth Boris Sepesi Stephen G Swisher Ara A Vaporciyan Garrett L Walsh David C Rice Wayne L Hofstetter

Ann Thorac Surg 2020 Oct 28. Epub 2020 Oct 28.

Department of Thoracic and Cardiovascular Surgery, University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, Texas, USA 77030. Electronic address:

Background: We have previously demonstrated that Enhanced Recovery After Surgery protocols are associated with a reduction in pulmonary complications. As a component of enhanced recovery pathways, intercostal nerve blocks with liposomal bupivacaine are increasingly utilized, but the extent to which this element may contribute to such outcomes has not been evaluated.

Methods: Patients undergoing lung resection for stage I-III non-small cell lung cancer at a single institution from 2006-2017 were examined for major postoperative pulmonary morbidity, defined as pneumonia, acute respiratory distress syndrome, respiratory arrest, reintubation, bronchoscopy, or need for discharge with oxygen. Pharmacy records were queried for administration of liposomal bupivacaine via posterior intercostal nerve block. Patients treated with and without liposomal bupivacaine were compared in a logistic regression to determine the impact upon pulmonary morbidity.

Results: 2865 patients were identified, including 860 (30%) who were treated with liposomal bupivacaine via posterior intercostal block. Pulmonary morbidity occurred in 455 (16%). Adoption of liposomal bupivacaine analgesia occurred over several years, beginning in 2012 to full adoption by 2017. Liposomal bupivacaine management was associated with a reduction in pulmonary complications, as compared to nonuse (odds ratio, 0.63, p=0.006). Additional factors associated with the occurrence of pulmonary morbidity were age, body mass index, smoking, spirometry values, and operative blood loss.

Conclusions: As a component of an active enhanced recovery program, liposomal bupivacaine is associated with a reduction in major pulmonary complications, and utilization should be evaluated on a hospital-by-hospital basis.
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http://dx.doi.org/10.1016/j.athoracsur.2020.09.017DOI Listing
October 2020

Consensus for Thoracoscopic Left Upper Lobectomy-Essential Components and Targets for Simulation.

Authors:
Darren S Bryan Mark K Ferguson Mara B Antonoff Leah M Backhus Thomas J Birdas Shanda H Blackmon Daniel J Boffa Andrew C Chang Gary W Chmielewski David T Cooke Jessica S Donington Henning A Gaissert Jeffrey A Hagen Wayne L Hofstetter Michael S Kent Ki Wan Kim Seth B Krantz Jules Lin Linda W Martin Shari L Meyerson John D Mitchell Daniela Molena David D Odell Mark W Onaitis Varun Puri Joe B Putnam Christopher W Seder Joseph B Shrager Harmik J Soukiasian Brendon M Stiles Betty C Tong Nirmal K Veeramachaneni

Ann Thorac Surg 2020 Oct 27. Epub 2020 Oct 27.

Department of Cardiovascular and Thoracic Surgery, University of Kansas Health System, Kansas City, Kansas.

Background: Simulation-based training is a valuable component of cardiothoracic surgical education. Effective curriculum development requires consensus on procedural components and focused attention on specific learning objectives. Through use of a Delphi process, we established consensus on the steps of video-assisted thoracoscopic surgery (VATS) left upper lobectomy and identified targets for simulation.

Methods: Experienced thoracic surgeons were randomly selected for participation. Surgeons voted and commented on the necessity of individual steps comprising VATS left upper lobectomy. Steps with greater than 80% of participants in agreement of their necessity were determined to have established "consensus." Participants voted on the physical or cognitive complexity of each, or both, and chose steps most amenable to focused simulation.

Results: Thirty thoracic surgeons responded and joined in the voting process. Twenty operative steps were identified, with surgeons reaching consensus on the necessity of 19. Components deemed most difficult and amenable to simulation included those related to dissection and division of the bronchus, artery, and vein.

Conclusions: Through a Delphi process, surgeons with a variety of practice patterns can achieve consensus on the operative steps of left upper lobectomy and agreement on those most appropriate for simulation. This information can be implemented in the development of targeted simulation for VATS lobectomy.
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http://dx.doi.org/10.1016/j.athoracsur.2020.06.152DOI Listing
October 2020

Esophageal adenocarcinoma with any component of signet ring cells portends poor prognosis and response to neoadjuvant therapy.

Authors:
Erin M Corsini Wai Chin Foo Kyle G Mitchell Nicolas Zhou Dipen M Maru Jaffer A Ajani Wayne L Hofstetter Arlene M Correa Mara B Antonoff Steven H Lin Reza J Mehran Ravi Rajaram David C Rice Jack A Roth Boris Sepesi Stephen G Swisher Ara A Vaporciyan Garrett L Walsh

J Thorac Cardiovasc Surg 2020 Sep 5. Epub 2020 Sep 5.

Department of Thoracic and Cardiovascular Surgery, University of Texas MD Anderson Cancer Center, Houston, Tex.

Background: Multiple investigations have shown inferior outcomes for esophageal cancer patients with signet ring cell (SRC) histology. Traditionally, SRC adenocarcinoma has been defined by ≥50% of the tumor composed of SRC. We hypothesized that patients with SRC even <50% would show resistance to standard multimodality therapy with poorer long-term outcomes.

Methods: Patients treated with trimodality therapy for adenocarcinoma from 2006 to 2018 were evaluated for SRC on pretreatment biopsy specimens. Available hematoxylin and eosin slides containing SRC tumors were re-reviewed by an esophageal pathologist to quantify the percent composition of SRC.

Results: SRC histology was identified on at least 1 pathologic specimen in 106 of 819 (13%) patients. Rates of pathologic complete response (pCR) among usual-type and SRC tumors were 25% (177/713) and 10% (11/106), respectively (P = .006). The pretreatment SRC components did not independently affect the rate of pCR (1%-10% SRC: 4% [2/46] pCR; 11%-49% SRC: 25% [7/28] pCR; 50%-100% SRC: 7% [2/30] pCR). Kaplan-Meier analysis demonstrated worse survival among patients with any degree of SRC present on pretreatment biopsy, as compared with usual-type esophageal adenocarcinoma (P < .0001). Cox multivariable analysis failed to identify a relationship between increasing SRC component and poorer survival.

Conclusions: We present the only known evaluation of the percentage of SRC component in esophageal carcinoma. Our data support the hypothesis that esophageal adenocarcinoma with any component of SRC are more resistant to chemoradiation with poorer survival. Pathologic reporting of esophageal adenocarcinoma should include any component of SRC. Alternative therapies in patients with any SRC component may be indicated.
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http://dx.doi.org/10.1016/j.jtcvs.2020.08.108DOI Listing
September 2020

Perioperative outcomes among chronic opioid users who receive lobectomy for non-small cell lung cancer.

Authors:
David B Nelson Jiangong Niu Kyle G Mitchell Mara B Antonoff Sharon H Giordano Wayne L Hofstetter Ara A Vaporciyan Boris Sepesi Reza J Mehran David C Rice

J Thorac Cardiovasc Surg 2020 02 27;159(2):691-702.e5. Epub 2019 Sep 27.

Department of Thoracic and Cardiovascular Surgery, The University of Texas MD Anderson Cancer Center, Houston, Tex. Electronic address:

Objective: We sought to identify whether chronic opioid users are at increased risk for complications or hospital readmission following lobectomy for non-small cell lung cancer.

Methods: The National Cancer Institute Surveillance, Epidemiology, and End Results-Medicare database was queried to identify patients older than age 65 years who received a lobectomy for non-small cell lung cancer. Chronic opioid users were identified through Medicare Part D records and were defined as those with >120 cumulative days of opioid supply for the year before surgery. A systematic 1:2 propensity matching was performed among chronic opioid users.

Results: Six thousand four hundred thirty-seven patients were identified, among whom 3627 (56%) were opioid naïve, 1866 (29%) were intermittent opioid users, and 944 (15%) were chronic opioid users. After propensity matching, 30-day mortality and 90-day mortality were nearly 2-fold higher among chronic opioid users compared with nonchronic users. In addition, length of stay and hospital charges were increased among chronic opioid users (median, 6 vs 7 days and mean increase, $12,526, respectively). Multivariable analysis revealed that intermittent opioid users and chronic opioid users were associated with an increased risk of 90-day hospital readmission compared with opioid-naïve patients (odds ratio, 1.35; 95% confidence interval, 1.07-1.71 and odds ratio, 1.72; 95% confidence interval, 1.40-2.12, respectively), predominantly burdened by infectious, renal, and pulmonary causes.

Conclusions: Patients who chronically use opioids before lobectomy represent high-risk patients. The risk of 30- and 90-day mortality, length of stay, hospital charges, and 90-day readmission after lobectomy among chronic opioid users are substantially elevated.
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http://dx.doi.org/10.1016/j.jtcvs.2019.09.059DOI Listing
February 2020

Postoperative Bleeding and Acute Kidney Injury in Esophageal Cancer Patients Receiving Ketorolac.

Authors:
Erin M Corsini Nicolas Zhou Mara B Antonoff Reza J Mehran David C Rice Jack A Roth Boris Sepesi Stephen G Swisher Ara A Vaporciyan Garrett L Walsh Wayne L Hofstetter

Ann Thorac Surg 2021 04 24;111(4):1111-1117. Epub 2020 Sep 24.

Department of Thoracic and Cardiovascular Surgery, University of Texas MD Anderson Cancer Center, Houston, Texas. Electronic address:

Background: As strategies promoting enhanced recovery protocols and opioid minimization techniques are increasingly prioritized, use of nonsteroidal antiinflammatory drugs continues to rise. Whether this prevalent use poses increased risk for bleeding or renal dysfunction in surgical populations after extensive dissection and fluid shifts is unclear.

Methods: We reviewed records of patients undergoing esophagectomy for a diagnosis of esophageal adenocarcinoma at a single institution from 2006 to 2018 for ketorolac administration during the postoperative hospital admission, as well as the occurrence of postoperative events, defined as the need for blood product transfusion and/or acute kidney injury.

Results: We identified 1019 patients, 123 of whom experienced postoperative events (12%). Ketorolac was administered to 686 (67%). Furthermore, ketorolac use steadily increased over the study period; 36 of 72 patients received this medication in 2006 (49%), and 76 of 83 in 2018 (92%). Multivariable logistic regression failed to identify a relationship between ketorolac administration (assessed as a binary covariate) and postoperative events (P = .657). Additional examination for a dose-response relationship using the cumulative total dose from the time of surgery to discharge also did not demonstrate a relationship with postoperative events (P = .829). In an effort to evaluate a more homogeneous population, we performed a subgroup analysis using only patients treated with trimodality therapy, which showed similar findings.

Conclusions: Ketorolac has become a staple of multimodal postesophagectomy analgesic regimens. Importantly, this medication does not pose risk for acute kidney injury or bleeding after surgery.
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http://dx.doi.org/10.1016/j.athoracsur.2020.07.028DOI Listing
April 2021

Management of Locally Advanced Esophageal Cancer.

Authors:
Nicolas Zhou Ravi Rajaram Wayne L Hofstetter

Surg Oncol Clin N Am 2020 Oct 21;29(4):631-646. Epub 2020 Jul 21.

Department of Thoracic and Cardiovascular Surgery, University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77005, USA. Electronic address:

Management of locally advanced esophageal cancer is evolving. Trimodality therapy with chemoradiation followed by surgical resection has become the standard of care. However, the value of planned surgery after response to therapy is in question. In this article, we discuss the current practice principles and evidence for the treatment of locally advanced esophageal cancer. Topics will include various neoadjuvant therapies, trimodality versus bimodality therapy, and outcomes for salvage esophagectomies. In addition, emerging novel therapies, such as HER2 inhibitors and immunotherapy, are available for unresectable or metastatic disease, enabling a greater armamentarium of tumor biology-specific treatments.
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http://dx.doi.org/10.1016/j.soc.2020.06.003DOI Listing
October 2020

Pathological nodal disease defines survival outcomes in patients with lung cancer with tumour major pathological response following neoadjuvant chemotherapy.

Authors:
Erin M Corsini Annikka Weissferdt Apar Pataer Nicolas Zhou Mara B Antonoff Wayne L Hofstetter Reza J Mehran Ravi Rajaram David C Rice Jack A Roth Ara A Vaporciyan Garrett L Walsh Tina Cascone John V Heymach Stephen G Swisher Boris Sepesi

Eur J Cardiothorac Surg 2021 Jan;59(1):100-108

Department of Thoracic and Cardiovascular Surgery, University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Objectives: Major pathological response (MPR) is prognostic of outcomes for patients with non-small-cell lung cancer following neoadjuvant chemotherapy and is used as the primary end point in neoadjuvant immunotherapy trials. We studied the influence of pathological nodal disease on patterns and timing of recurrence among patients with MPR.

Methods: Patients treated with neoadjuvant chemotherapy for stages I-III non-small-cell lung cancer were identified. Surgical specimens were histopathologically examined for tumour viability, categorized as ≤10% viability (MPR) or >10% (NoMPR). Overall survival and disease-free survival were evaluated with emphasis upon MPR and pathological nodal disease.

Results: Among 307 patients, 58 (19%) had MPR within primary tumour and 42 (14%) had MPRypN0. In the MPR group, the frequency of cN0 and cN+ disease was 18 (31%) and 40 (69%); similarly, the frequency of ypN0, ypN1 and ypN2 was 72% (42/58), 16% (9/58) and 12% (7/58), respectively. When evaluating only those with MPR, recurrence rates among those with MPRypN0, MPRypN1 and MPRypN2 were 33% (14/42), 44% (4/9) and 71% (5/7) (P = 0.16). The median time-to-recurrence in MPRypN0, MPRypN1 and MPRypN2 was 40, 10 and 14 months (P = 0.006). Distant recurrences were less common among those with MPRypN0 [MPRypN0, 26% (11/42); MPRypN1, 44% (4/9); MPRypN2, 71% (5/7); P = 0.047]. Though the median disease-free survival was prolonged among those with MPR vs NoMPR (120 vs 25 months, P < 0.0001), only those with MPRypN0 had prolonged disease-free survival in comparison to other groups upon pairwise comparisons, while MPRypN+ experienced no benefit.

Conclusions: MPRypN0 represents the most favourable surrogate end point following neoadjuvant chemotherapy. Patients with ypN1-2 are at the risk of early recurrence regardless of primary tumour MPR, warranting intensive surveillance and consideration for additional adjuvant therapy. We highlight that MPRypN0 is the most rigorous end point and should be considered as a surrogate end point in future neoadjuvant trials.
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http://dx.doi.org/10.1093/ejcts/ezaa290DOI Listing
January 2021

Modified En Bloc Esophagectomy Compared With Standard Resection After Neoadjuvant Chemoradiation.

Authors:
Erin M Corsini Kyle G Mitchell Nicolas Zhou Mara B Antonoff Reza J Mehran David C Rice Jack A Roth Boris Sepesi Stephen G Swisher Ara A Vaporciyan Garrett L Walsh Dipen M Maru Steven H Lin Jaffer A Ajani Wayne L Hofstetter

Ann Thorac Surg 2021 04 25;111(4):1133-1140. Epub 2020 Aug 25.

Department of Thoracic and Cardiovascular Surgery, University of Texas MD Anderson Cancer Center, Houston, Texas. Electronic address:

Background: Surgeons have shifted away from the practice of en bloc esophagectomy, particularly in the era of neoadjuvant therapies. Although some still advocate for this radical approach, contemporary data establishing its superiority are sparse. We hypothesized that a more complete, radical resection could be completed in the setting of chemoradiation without adding morbidity.

Methods: Patients undergoing esophagectomy after neoadjuvant chemoradiation for esophageal adenocarcinoma from 2006-2018 were evaluated. Outcomes after right transthoracic en bloc esophagectomy were compared with standard esophagectomy to determine the impact on outcomes. A Cox proportional hazard model was evaluated, and logistic regression was performed to determine the impact of en bloc resection on postoperative morbidity.

Results: A total of 604 patients were identified, including 133 (22%) who underwent modified en bloc esophagectomy. Positive margins were most likely to occur in standard esophagectomy (35 of 471, 7%) vs en bloc (3 of 133, 2%) (P = .026). En bloc resection yielded a greater lymph node harvest (27; interquartile range, 22-36), as compared to standard esophagectomy (22; interquartile range, 17-28), P < .001. Multivariable analysis demonstrated prolonged progression-free survival with en bloc resection (hazard ratio, 0.74; P = .041), with 3-year freedom from locoregional recurrences of 78% and 90% for standard and en bloc approaches (P = .044). There were no differences in cardiopulmonary, gastrointestinal, or wound complications, as well as leak or chylothorax.

Conclusions: Our experience demonstrates improved locoregional disease control with en bloc esophagectomy, with equivalent morbidity. Although these results may be multifactorial, including adequate clearance of both primary tumor and nodal micrometastases, this approach is safe and feasible.
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http://dx.doi.org/10.1016/j.athoracsur.2020.06.054DOI Listing
April 2021

ISDE presidential Bio; Tom R DeMeester, fourth president of the ISDE.

Authors:
Wayne L Hofstetter

Dis Esophagus 2020 Aug;33(8)

Department of Thoracic and Cardiovascular Surgery, University of Texas, MD Anderson Cancer Center, Houston, TX.

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http://dx.doi.org/10.1093/dote/doaa065DOI Listing
August 2020

Total Lesion Glycolysis Assessment Identifies a Patient Fraction With a High Cure Rate Among Esophageal Adenocarcinoma Patients Treated With Definitive Chemoradiation.

Authors:
Kazuto Harada Carol C Wu Xuemei Wang Dilsa Mizrak Kaya Fatemeh G Amlashi Masaaki Iwatsuki Mariela A Blum Murphy Dipen M Maru Brian Weston Jeffrey H Lee Jane E Rogers Irene Thomas Namita Shanbhag Manoop S Bhutani Wayne L Hofstetter Quynh-Nhu Nguyen Jaffer A Ajani

Ann Surg 2020 08;272(2):311-318

Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX.

Objective: We aimed to determine whether tumor metabolism could be prognostic of cure in L-EAC patients who receive definitive chemoradiation.

Summary Background Data: Patients with inoperable localized esophageal adenocarcinoma (L-EAC) often receive definitive chemoradiation; however, biomarkers and/or imaging variables to prognosticate cure are missing.

Methods: Two hundred sixty-six patients with L-EAC who had chemoradiation but not surgery were analyzed from the prospectively maintained EAC databases in the Department of Gastrointestinal Medical Oncology at The University of Texas MD Anderson Cancer Center (Texas, USA) between March 2002 and April 2015. Maximum standardized uptake value (SUVmax) and total lesion glycolysis (TLG) from the positron emission tomography data were evaluated.

Results: Of 266 patients, 253 (95%) were men; the median age was 67 years (range 20-91 yrs) and 153 had poorly differentiated L-EAC. The median SUVmax was 10.3 (range 0-87) and the median TLG was 85.7 (range 0-3227). Both SUVmax and TLG were higher among those with: tumors >5 cm in length, high clinical stage, and high tumor and node categories by TNM staging (all P < 0.0001). Of 234 patients evaluable for cure, 60 (25.6%) achieved cure. In the multivariable logistic regression model, low TLG (but not low SUVmax) was associated with cure (continuous TLG value: odds ratio 0.70, 95% confidence interval (CI) 0.54-0.92). TLG was quantified into 4 quartile categorical variables; first quartile (Q1; <32), second quartile (Q2; 32.0-85.6), third quartile (Q3; 85.6-228.4), and fourth quartile (Q4; >228.4); the cure rate was only 10.3% in Q4 and 5.1% in Q3 but increased to 28.8% in Q2, and 58.6% in Q1. The cross-validation resulted in an average accuracy of prediction score of 0.81 (95% CI, 0.75-0.86).

Conclusions: In this cross-validated model, 59% of patients in the 1st quartile were cured following definitive chemoradiation. Baseline TLG could be pursued as one of the tools for esophageal preservation.
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http://dx.doi.org/10.1097/SLA.0000000000003228DOI Listing
August 2020

Peripheral cytokines are not influenced by the type of surgical approach for non-small cell lung cancer by four weeks postoperatively.

Authors:
Erin M Corsini Qi Wang Hai T Tran Kyle G Mitchell Mara B Antonoff Wayne L Hofstetter Reza J Mehran David C Rice Jack A Roth Stephen G Swisher Ara A Vaporciyan Garrett L Walsh Alexandre Reuben Mayra E Vasquez Chantale Bernatchez Jing Wang Tina Cascone Jianjun Zhang John V Heymach Don L Gibbons Cara L Haymaker Boris Sepesi

Lung Cancer 2020 08 27;146:303-309. Epub 2020 Jun 27.

Department of Thoracic and Cardiovascular Surgery, University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX, United States. Electronic address:

Objectives: The influence of surgical approach on systemic inflammatory response and the subsequent oncologic impact for non-small cell lung cancer is debated. We aimed to measure the effects of thoracic surgical approach on peripheral cytokine milieu over time.

Methods: Patients undergoing primary lung resection without neoadjuvant therapy (2016-2018) were evaluated. A panel of 43 cytokines, angiogenic factors, and inflammatory molecules (CAFs) were evaluated in peripheral blood preoperatively, at 24 -hs and 4-weeks postoperatively. Differences between CAFs in patients undergoing thoracotomy versus video-assisted thoracoscopic surgery (VATS) at all timepoints were assessed using Student's t-test.

Results: 76 patients with available peripheral CAF panels met inclusion criteria. Thoracotomy was performed in 53 (70 %) patients while VATS was undertaken in 23 (30 %). Upon examination of known inflammatory CAFs, including IL-1β, IL-6, IL-8, IL-10, IFN-γ, and soluble (s) CD27, no differences were detected at 24 h or 4 weeks postoperatively between surgical groups. Examination of trends over time did not demonstrate any temporal derangements for these CAFs, with return to baseline levels by 4 weeks postoperatively for both groups. Evaluation of soluble (s) checkpoint molecules, including sPD-1, sPD-L1, sTIM-3, and sCTLA-4, did not reveal any differences in the immediate postoperative or long-term recovery period.

Conclusions: Peripheral immune profiles following pulmonary resection do not appear to differ between VATS and thoracotomy postoperatively. CAF fluctuations are transient and recover rapidly. These results, at the peripheral cytokine level, suggest that the surgical approach for lung cancer is unlikely to alter the effectiveness of novel immune-modulating systemic therapies, although more studies are needed to validate these findings.
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http://dx.doi.org/10.1016/j.lungcan.2020.06.022DOI Listing
August 2020

Treatment of Locally Advanced Esophageal Carcinoma: ASCO Guideline.

Authors:
Manish A Shah Erin B Kennedy Daniel V Catenacci Dana C Deighton Karyn A Goodman Narinder K Malhotra Christopher Willett Brendon Stiles Prateek Sharma Laura Tang Bas P L Wijnhoven Wayne L Hofstetter

J Clin Oncol 2020 08 22;38(23):2677-2694. Epub 2020 Jun 22.

The University of Texas MD Anderson Cancer Center, Houston, TX.

Purpose: To develop an evidence-based clinical practice guideline to assist in clinical decision making for patients with locally advanced esophageal cancer.

Methods: ASCO convened an Expert Panel to conduct a systematic review of the more recently published literature (1999-2019) on therapy options for patients with locally advanced esophageal cancer and provide recommended care options for this patient population.

Results: Seventeen randomized controlled trials met the inclusion criteria. Where possible, data were extracted separately for squamous cell carcinoma and adenocarcinoma.

Recommendations: Multimodality therapy for patients with locally advanced esophageal carcinoma is recommended. For the subgroup of patients with adenocarcinoma, preoperative chemoradiotherapy or perioperative chemotherapy should be offered. For the subgroup of patients with squamous cell carcinoma, preoperative chemoradiotherapy or chemoradiotherapy without surgery should be offered. Additional subgroup considerations are provided to assist with implementation of these recommendations. Additional information is available at www.asco.org/gastrointestinal-cancer-guidelines.
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http://dx.doi.org/10.1200/JCO.20.00866DOI Listing
August 2020

Importance of resection for locoregional disease control in Masaoka stage IVA thymic neoplasms.

Authors:
Erin M Corsini Kyle G Mitchell Wayne L Hofstetter Reza J Mehran Jack A Roth Boris Sepesi Stephen G Swisher Ara A Vaporciyan Garrett L Walsh Mara B Antonoff David C Rice

J Surg Oncol 2020 Sep 28;122(3):515-522. Epub 2020 May 28.

Department of Thoracic and Cardiovascular Surgery, University of Texas MD Anderson Cancer Center, Houston, Texas.

Background And Objectives: It is unclear if a specific strategy for simultaneous treatment of primary thymic neoplasms and pleural metastases confers benefit for Masaoka stage IVA disease. We reviewed our experience with thymic neoplasms with concurrent pleural metastases to identify factors influencing outcomes.

Methods: Records of patients who presented with stage IVA thymic neoplasms from 2000 to 2018 were assessed. Multivariate Cox proportional hazards analyses were completed to determine predictors of progression-free and overall survival.

Results: Forty-eight patients were identified, including 34 (71%) who underwent surgery. Median overall and progression-free survival were 123 and 21 months, respectively. The extent of resection varied, and was most commonly thymectomy plus partial pleurectomy (22, 65%). Median progression-free survival for patients who underwent surgical resection versus those who had not was 24 versus 12 months (P = .018). Following surgical resection, mediastinal recurrence was uncommon (2, 6%, vs 7, 50% nonoperatively). Five-year survival rates in these groups were suggestive of possible benefit to surgery (87% vs 68%).

Conclusions: Thymic neoplasms with pleural dissemination represents a treatment challenge. As part of a multidisciplinary approach, surgery appears to be associated with more favorable long-term results, although selection bias may account for some of the survival differences observed.
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http://dx.doi.org/10.1002/jso.25981DOI Listing
September 2020

Time trends and predictors of survival in surgically resected early-stage non-small cell lung cancer patients.

Authors:
Jitesh B Shewale Erin M Corsini Arlene M Correa Eric L Brown Luis G Leon-Novelo Alan G Nyitray Mara B Antonoff Wayne L Hofstetter Reza J Mehran David C Rice Jack Roth Garrett L Walsh Ara A Vaporciyan Stephen G Swisher Boris Sepesi

J Surg Oncol 2020 Sep 30;122(3):495-505. Epub 2020 Apr 30.

Department of Thoracic and Cardiovascular Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas.

Background: The improvement in the management of lung cancer have the potential to improve survival in patients undergoing resection for early-stage (stage I and II) non-small cell lung cancer (NSCLC), but few studies have evaluated time trends and identified predictors of overall survival (OS).

Methods: We identified surgically resected early-stage NSCLC between 1998 and 2016. The 3-year OS (1998-2014) and 5-year OS (1998-2012) rates were calculated for each year. Joinpoint regression was used to calculate annual percentage changes (APC) and to test time trends in OS. Multivariable Cox regression was used to identify predictors of OS.

Results: There was a significant upward trend in the 3-year (1998, 56%; 2014, 83%; APC = 1.8) and 5-year (1998, 47%; 2012, 76%; APC = 3.1) OS. Older age; male sex; history of diabetes, coronary artery disease, and chronic obstructive pulmonary disease; high ASA score; smoking pack-years; high-grade tumor; pneumonectomy; thoracotomy; neoadjuvant therapy; nodal disease; and positive tumor margin were predictors of poor OS.

Conclusion: The upward time trend in OS suggests that improved staging, patient selection, and management have conferred a survival benefit in early-stage NSCLC patients. The prediction model of OS could be used to refine selection criteria for resection and improve survival outcomes.
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http://dx.doi.org/10.1002/jso.25966DOI Listing
September 2020

Brain metastases in patients with upper gastrointestinal cancer is associated with proximally located adenocarcinoma and lymph node metastases.

Authors:
Kazuto Harada Hyunsoo Hwang Xuemei Wang Ahmed Abdelhakeem Masaaki Iwatsuki Mariela A Blum Murphy Dipen M Maru Brian Weston Jeffrey H Lee Jane E Rogers Allison Trail Namita Shanbhag Meina Zhao Manoop S Bhutani Quynh-Nhu Nguyen Stephen G Swisher Naruhiko Ikoma Prajnan Das Wayne L Hofstetter Brian D Badgwell Jaffer A Ajani

Gastric Cancer 2020 09 28;23(5):904-912. Epub 2020 Apr 28.

Departments of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX, 77030, USA.

Background: As cancer patients are surviving longer, more patients manifest brain metastases (BRMs). However, the rate of BRMs from upper gastrointestinal cancer is unclear. We therefore evaluated the frequency and prognostic effect of BRMs in this setting.

Methods: We analyzed records of 2348 patients who were treated between January 2002 and December 2016 for upper gastrointestinal cancer, including esophageal and gastroesophageal junction adenocarcinoma (EAC; proximal EAC, Siewert types I and II), esophageal squamous cell carcinoma (ESCC), and gastric adenocarcinoma (GAC; Siewert type III and stomach cancer) in our Gastrointestinal Medical Oncology Database. Frequency, risk factors, and survival after BRMs were evaluated.

Results: Of 2348 patients, 68 (2.9%) had BRMs upon follow-up. The BRM rates were as follows: proximal EAC, 4.8%; Siewert type I, 5.9%; Siewert type II, 2.2%; Siewert type III, 0.7%; ESCC: 1.2%; and stomach cancer, 0%. Among EAC patients, Siewert type I and lymph node metastases were independent the risk factors for BRMs in the multivariable analysis. The median overall survival (OS) in the 68 patients with BRMs was only 1.16 years (95% CI 0.78-1.61). However, OS for patients who had a solitary BRM, who had BRM but no other distant metastasis, or who underwent surgery or stereotactic radiosurgery favorable.

Conclusion: Patients with proximally located adenocarcinoma, or with lymph node metastases are at a higher risk for BRMs and patients fare better after treatment of isolated BRM.
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http://dx.doi.org/10.1007/s10120-020-01075-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7442686PMC
September 2020

Ketorolac use and anastomotic leak in patients with esophageal cancer.

Authors:
Erin M Corsini Wayne L Hofstetter

J Thorac Cardiovasc Surg 2021 02 21;161(2):448-454. Epub 2020 Mar 21.

Department of Thoracic and Cardiovascular Surgery, University of Texas MD Anderson Cancer Center, Houston, Tex; Department of Anesthesiology and Perioperative Medicine, University of Texas MD Anderson Cancer Center, Houston, Tex.

Objectives: Recent evidence has shown an association between postoperative ketorolac use and anastomotic leak in patients undergoing intestinal and colorectal operations, but this relationship has been minimally explored after esophagectomy. As the use of nonopioid pain control and enhanced recovery protocols is increasingly prioritized, determination of a possible correlation between perioperative ketorolac use and leak is essential.

Methods: Records of patients undergoing esophagectomy for adenocarcinoma at a single institution from 2006 to 2018 reviewed for occurrence of anastomotic leak. Institutional pharmacy records were queried for ketorolac administration during the surgical case through the time of discharge. Multivariable logistic regression was used to determine the relationship between ketorolac administration and anastomotic leak.

Results: A total of 1019 patients met inclusion criteria, the majority of whom were male (907, 89%) with a median age of 62 years. Patients predominantly presented with locoregionally advanced disease and were treated with initial chemoradiation. Ketorolac was administered to 686 patients (67%); use was observed to increase over the study period from 49% in 2006 to 92% in 2016. Conversely, anastomotic leak occurred in 87 patients (9%) overall and decreased over time from 15% (11/72) in 2006 to 2% (2/83) in 2018. Upon multivariable analysis, neither ketorolac administration evaluated as a categoric variable (odds ratio, 0.99; P = .958) or as a continuous variable using dose (odds ratio, 1.00; P = .843) demonstrated an association with anastomotic leak.

Conclusions: Ketorolac in the postoperative period after esophagectomy has become an integral component of enhanced recovery pathways and does not appear to be associated with anastomotic leak.
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http://dx.doi.org/10.1016/j.jtcvs.2020.02.133DOI Listing
February 2021

F-fluorodeoxyglucose positron emission tomography correlates with tumor immunometabolic phenotypes in resected lung cancer.

Authors:
Kyle G Mitchell Behrang Amini Yunfei Wang Brett W Carter Myrna C B Godoy Edwin R Parra Carmen Behrens Pamela Villalobos Alexandre Reuben J Jack Lee Annikka Weissferdt Cesar A Moran Junya Fujimoto Boris Sepesi Garrett L Walsh Ara A Vaporciyan Wayne L Hofstetter William N William Don L Gibbons Jing Wang Patrick Hwu Stephen G Swisher David Piwnica-Worms Humam Kadara Ignacio I Wistuba John V Heymach Weiyi Peng Tina Cascone

Cancer Immunol Immunother 2020 Aug 16;69(8):1519-1534. Epub 2020 Apr 16.

Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit 432, Houston, TX, 77030, USA.

Enhanced tumor glycolytic activity is a mechanism by which tumors induce an immunosuppressive environment to resist adoptive T cell therapy; therefore, methods of assessing intratumoral glycolytic activity are of considerable clinical interest. In this study, we characterized the relationships among tumor F-fluorodeoxyglucose (FDG) retention, tumor metabolic and immune phenotypes, and survival in patients with resected non-small cell lung cancer (NSCLC). We retrospectively analyzed tumor preoperative positron emission tomography (PET) F-FDG uptake in 59 resected NSCLCs and investigated correlations between PET parameters (SUV, SUV, SUV, TLG), tumor expression of glycolysis- and immune-related genes, and tumor-associated immune cell densities that were quantified by immunohistochemistry. Tumor glycolysis-associated immune gene signatures were analyzed for associations with survival outcomes. We found that each F-FDG PET parameter was positively correlated with tumor expression of glycolysis-related genes. Elevated F-FDG SUV was more discriminatory of glycolysis-associated changes in tumor immune phenotypes than other F-FDG PET parameters. Increased SUV was associated with multiple immune factors characteristic of an immunosuppressive and poorly immune infiltrated tumor microenvironment, including elevated PD-L1 expression, reduced CD57 cell density, and increased T cell exhaustion gene signature. Elevated SUV identified immune-related transcriptomic signatures that were associated with enhanced tumor glycolytic gene expression and poor clinical outcomes. Our results suggest that F-FDG SUV has potential value as a noninvasive, clinical indicator of tumor immunometabolic phenotypes in patients with resectable NSCLC and warrants investigation as a potential predictor of therapeutic response to immune-based treatment strategies.
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http://dx.doi.org/10.1007/s00262-020-02560-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7997043PMC
August 2020

Preoperative Chemoradiation Versus Chemotherapy in Gastroesophageal Junction Adenocarcinoma.

Authors:
Syed Nabeel Zafar Mariela Blum Yi-Ju Chiang Jaffer A Ajani Jeannelyn S Estrella Prajnan Das Bruce D Minsky Wayne L Hofstetter Paul Mansfield Brian D Badgwell Naruhiko Ikoma

Ann Thorac Surg 2020 08 11;110(2):398-405. Epub 2020 Apr 11.

Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas. Electronic address:

Background: The incidence of lower esophageal and gastroesophageal junction adenocarcinoma has sharply increased over the past several decades and is a serious public health problem. Preoperative therapy with either chemotherapy or chemoradiation is recommended, but the optimal regimen is unknown. We used the National Cancer Database and propensity score matching to investigate whether preoperative chemoradiation therapy offers an advantage over chemotherapy alone for patients with these tumors.

Methods: From the National Cancer Database esophageal and gastric dataset, we selected patients with either lower esophageal or gastric cardia adenocarcinomas who had undergone definitive resection after chemotherapy or chemoradiation. We used propensity score matching to balance groups based on the preoperative treatment they received. We then used conditional multivariable logistic regression and Cox proportional hazard models to examine the association between preoperative therapy regimen and pathological response, overall survival (OS), and postoperative outcomes.

Results: Our study included 13,783 patients; 12,129 (89.0%) had received preoperative chemoradiation. Propensity score matching created 1650 pairs. Patients receiving chemoradiation were 2.7 (95% confidence interval, 1.29-3.23) times more likely to achieve complete response in the primary tumor than were those receiving chemotherapy alone; however, chemoradiation was not associated with improved OS (hazard ratio, 1.01; 95% confidence interval, 0.91-1.12). Short-term outcomes (length of stay, mortality, and readmissions) were similar between the 2 groups.

Conclusions: Preoperative chemoradiation was associated with a higher complete response rate in the primary tumor but not with improved OS in lower esophageal and gastroesophageal junction adenocarcinoma.
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http://dx.doi.org/10.1016/j.athoracsur.2020.03.024DOI Listing
August 2020