Prognostic value of circumferential radial margin involvement in esophagectomy for esophageal cancer: a case series.

BACKGROUND: Residual tumor at the proximal or distal margin after esophagectomy is associated with worse survival outcomes; however, the significance of the circumferential resection margin (CRM) remains controversial. In this study, we sought to evaluate the prognostic significance of the CRM in patients with esophageal cancer undergoing resection. MATERIALS AND METHODS: We identified patients who underwent esophagectomy for pathologic T3 esophageal cancer from 2000 to 2019. Patients were divided into three groups: CRM- (residual tumor >1 mm from the CRM), CRM-close (residual tumor >0 to 1 mm from the CRM), and CRM+ (residual tumor at the surgical CRM). CRM was also categorized and analyzed per the Royal College of Pathologists (RCP) and College of American Pathologists (CAP) classifications. RESULTS: Of the 519 patients included, 351 (68%) had CRM-, 132 (25%) had CRM-close, and 36 (7%) had CRM+. CRM+ was associated with shorter disease-free survival [DFS; CRM+ vs. CRM-: hazard ratio (HR), 1.53 [95% CI, 1.03-2.28]; P =0.034] and overall survival (OS; CRM+ vs. CRM-: HR, 1.97 [95% CI, 1.32-2.95]; P <0.001). Survival was not significantly different between CRM-close and CRM-. After adjustment for potential confounders, CAP+ was associated with poor oncologic outcomes (CAP+ vs. CAP-: DFS: HR, 1.47 [95% CI, 1.00-2.17]; P =0.050; OS: HR, 1.93 [95% CI, 1.30-2.86]; P =0.001); RCP+ was not (RCP+ vs. RCP-: DFS: HR, 1.21 [95% CI, 0.97-1.52]; P =0.10; OS: HR, 1.21 [95% CI, 0.96-1.54]; P =0.11). CONCLUSION: CRM status has critical prognostic significance for patients undergoing esophagectomy: CRM+ was associated with worse outcomes, and outcomes between CRM-close and CRM- were similar.

Waiting to Operate: The Risk of Salvage Esophagectomy.

OBJECTIVE: To assess postoperative morbidity, disease-free survival (DFS), and overall survival (OS) in patients treated with salvage esophagectomy (SE). BACKGROUND DATA: A shift toward a "surgery as needed" approach for esophageal cancer has emerged, potentially resulting in delayed esophagectomy. METHODS: We identified patients with clinical stage I-III esophageal adenocarcinoma or squamous cell carcinoma who underwent chemoradiation followed by esophagectomy from 2001 to 2019. SE was defined as esophagectomy performed >90 days after chemoradiation ("for time") and esophagectomy performed for recurrence after curative-intent chemoradiation ("for recurrence"). The odds of postoperative serious complications were assessed by multivariable logistic regression. The relationship between SE and OS and DFS were quantified using Cox regression models. RESULTS: Of 1137 patients identified, 173 (15%) underwent SE. Of those, 61 (35%) underwent SE for recurrence, and 112 (65%) underwent SE for time. The odds of experiencing any serious complication [odds ratio, 2.10 (95% CI, 1.37-3.20); P =0.001] or serious pulmonary complication [odds ratio, 2.11 (95% CI, 1.31-3.42); P =0.002] were 2-fold higher for SE patients; SE patients had a 1.5-fold higher hazard of death [hazard ratio, 1.56 (95% CI, 1.25-1.94); P <0.0001] and postoperative recurrence [hazard ratio, 1.43 (95% CI, 1.16-1.77); P =0.001]. Five-year OS for nonsalvage esophagectomy was 45% [(95% CI, 41.6%-48.6%) versus 26.5% (95% CI, 20.2%-34.8%) for SE (log-rank P <0.001)]. Five-year OS for SE for time was 27.1% [(95% CI, 19.5%-37.5%) versus 25.2% (95% CI, 15.3%-41.5%) for SE for recurrence ( P =0.611)]. CONCLUSIONS: SE is associated with a higher risk of serious postoperative complications and shorter DFS and OS.

Translating Telemedicine to Thoracic Surgical Oncological Care: Performance Analysis and Patient Perceptions During the COVID-19 Pandemic.

OBJECTIVE: The objective is to determine how the COVID-19 pandemic affected care for patients undergoing thoracic surgery for cancer. BACKGROUND: The COVID-19 pandemic accelerated the adoption of telemedicine. METHODS: Characteristics and outcomes of new patients seen between March 1 and June 30, 2019, and the same period in 2020 were compared. Patients who did not undergo surgery were excluded. Patients who had a telemedicine visit (new and established) in the 2020 period were asked to complete a survey. RESULTS: In total, 624 new patients were seen in 2019 versus 299 in 2020 (52% reduction); 45% of patients (n=136) in 2020 were seen via telemedicine. There was no statistically significant difference in time to surgery, pathological upstaging, or postsurgical complications between 2019 and 2020. In total, 1085 patients (new and established) had a telemedicine visit in 2020; 239 (22%) completed the survey. A majority replied that telemedicine was equivalent to in-person care (77%), did not impair care quality (84%), resulted in less stress (69%) and shorter waits (86%), was more convenient (92%), saved money and commuting time (93%), and expanded who could attend visits (91%). Some patients regretted the loss of human interaction (71%). Most would opt for telemedicine after the pandemic (60%), although some would prefer in-person format for initial visits (55%) and visits with complex discussions (49%). Only 21% were uncomfortable with the telemedicine technology. CONCLUSIONS: Telemedicine enabled cancer care to continue during the COVID-19 pandemic without delays in surgery, cancer progression, or worsened postoperative morbidity and was generally well received.

Induction FOLFOX and PET-Directed Chemoradiation for Locally Advanced Esophageal Adenocarcinoma.

OBJECTIVE: To compare the efficacy and safety of induction FOLFOX followed by PET-directed nCRT, induction CP followed by PET-directed nCRT, and nCRT with CP alone in patients with EAC. SUMMARY OF BACKGROUND DATA: nCRT with CP is a standard treatment for locally advanced EAC. The results of cancer and leukemia group B 80803 support the use of induction chemotherapy followed by PET-directed chemo-radiation therapy. METHODS: We retrospectively identified all patients with EAC who underwent the treatments above followed by esophagectomy. We assessed incidences of pathologic complete response (pCR), near-pCR (ypN0 with ≥90% response), and surgical complications between treatment groups using Fisher exact test and logistic regression; disease-free survival (DFS) and overall survival (OS) were estimated by the Kaplan-Meier method and evaluated using the log-rank test and extended Cox regression. RESULTS: In total, 451 patients were included: 309 (69%) received induction chemotherapy before nCRT (FOLFOX, n = 70; CP, n = 239); 142 (31%) received nCRT with CP. Rates of pCR (33% vs. 16%, P = 0.004), near-pCR (57% vs. 33%, P < 0.001), and 2-year DFS (68% vs. 50%, P = 0.01) were higher in the induction FOLFOX group than in the induction CP group. Similarly, the rate of near-pCR (57% vs. 42%, P = 0.04) and 2-year DFS (68% vs. 44%, P < 0.001) were significantly higher in the FOLFOX group than in the no-induction group. CONCLUSIONS: Induction FOLFOX followed by PET-directed nCRT may result in better histopathologic response rates and DFS than either induction CP plus PET-directed nCRT or nCRT with CP alone.

Patterns and influence of nodal metastases after neoadjuvant chemoradiation and R0 resection in esophageal adenocarcinoma.

OBJECTIVE: Little is known about the pattern of nodal metastases in patients with esophageal adenocarcinoma who have received neoadjuvant chemoradiation and undergone surgery. We sought to assess this pattern and evaluate its association with prognosis. METHODS: All patients with esophageal adenocarcinoma who underwent neoadjuvant chemoradiation and R0 esophagectomy between 2010 and 2018 at our institution were included (n = 537). The primary objective was to evaluate the association of sites of lymph node metastases with disease-free survival. The number of nodal stations and individual sites of nodal metastases were evaluated first in univariable then in separate multivariable Cox regression models adjusted for clinical factors. RESULTS: Of 537 patients, 193 (36%) had pathologic nodal metastases at the time of surgery; 153 (28%) had single-station disease, 32 (6.0%) had 2-station disease, and 8 (1.5%) had 3-station disease. The majority of patients with multiple positive nodal stations had positive nodes in the paraesophageal (93%) and/or left gastric stations (60%). Multivariable models controlling for clinical factors showed that an increasing number of positive nodal stations (hazard ratio, 1.59; 95% CI, 1.35-1.84; P < .01)-in particular, the subcarinal (hazard ratio, 2.78; 95% CI, 1.54-5.03; P < .01) and paraesophageal stations (hazard ratio, 2.0; 95% CI, 1.58-2.54; P < .01)-was associated with increased risk of recurrence. CONCLUSIONS: One-third of patients who have undergone R0 resection for esophageal adenocarcinoma following induction chemoradiation therapy have metastatic lymph nodes. An increasing number of nodal stations, particularly paraesophageal and subcarinal metastases, were associated with increased risk of recurrence.

Efficacy of an Esophageal Spacer for Spine Radiosurgery: First Experience.

This is the first study to investigate the use of an esophageal hydrogel spacer in spine stereotactic radiosurgery. The tolerability and the dose reduction to the esophagus are predicted to reduce the incidence of high-grade toxicities, which in turn can permit dose escalation to optimize tumor control.

Early implementation of a perioperative nutrition support pathway for patients undergoing esophagectomy for esophageal cancer.

BACKGROUND: Unintentional weight loss and malnutrition are associated with poorer prognosis in patients with cancer. Risk of cancer-associated malnutrition is highest among patients with esophageal cancer (EC) and has been repeatedly shown to be an independent risk factor for worse survival in these patients. Implementation of nutrition protocols may reduce postoperative weight loss and enhance recovery in these patients. METHODS: We retrospectively identified all patients who underwent Ivor Lewis esophagectomy for EC from January 2015 to August 2019 from a prospectively collected institutional database. Patients who underwent surgery after the implementation of this protocol (September 2017-August 2019) were compared with patients who underwent resection before protocol implementation (January 2015-July 2017). Patients undergoing surgery during the month of protocol initiation were excluded. RESULTS: Of the 404 patients included in our study, 217 were in the preprotocol group, and 187 were in the postprotocol group. Compared with the preprotocol group, there were significant reductions in length of hospital stay (p < 0.001), time to diet initiation (p < 0.001), time to feeding tube removal (p = 0.012), and postoperative weight loss (p = 0.002) in the postprotocol group. There was no significant difference in the incidence of postoperative complications, 30-day readmission, or mortality rates between groups. CONCLUSIONS: Results of the present study suggest a standardized perioperative nutrition protocol may prevent unintentional weight loss and improve postoperative outcomes in patients with EC undergoing resection.

Treatment of Anastomotic Recurrence After Esophagectomy.

BACKGROUND: Isolated local recurrence after curative esophagectomy for esophageal cancer is a rare event. Although it is potentially curable, management can be challenging. METHODS: We retrospectively reviewed all patients undergoing esophagectomy for esophageal adenocarcinoma (EAC) from 2000 to 2019. Date of recurrence was defined as the date at which the initial abnormal surveillance study result or symptomatic presentation led to further workup and subsequent pathologic diagnosis of recurrence. Overall survival after recurrence was estimated using Kaplan-Meier methods and compared between treatment groups using the log-rank test. RESULTS: Of the 1370 patients with EAC who underwent esophagectomy in our cohort, 531 (39%) developed recurrence of their disease. The 5-year cumulative incidence of recurrence was 2.7% (95% CI, 2.0%-3.6%) for local, 6.3% (95% CI, 5.2%-7.8%) for regional, and 22.0% (95% CI, 20.0%-24.4%) for distant recurrences. On univariable and multivariable competing-risk regression analysis, advanced pT stage, signet ring histology, and serious complication were independently associated with local recurrence. Patients with local recurrence treated with definitive therapy had a median survival after recurrence of 19.1 months (95% CI, 11.4-33.2 months) compared with 10.6 months (95% CI, 8.5-14.2 months) for chemotherapy or radiotherapy alone and 1.73 months (95% CI, 0.23-15.6 months) for no treatment (P < .001). CONCLUSIONS: Isolated local recurrence occurred in only 3% of patients. Advanced T stage, signet cell histology, and serious complication were risk factors for recurrence. Although complex surgical resection is required, in very select cases, more aggressive treatment may be warranted.

Discovering the anti-cancer potential of non-oncology drugs by systematic viability profiling.

Anti-cancer uses of non-oncology drugs have occasionally been found, but such discoveries have been serendipitous. We sought to create a public resource containing the growth inhibitory activity of 4,518 drugs tested across 578 human cancer cell lines. We used PRISM, a molecular barcoding method, to screen drugs against cell lines in pools. An unexpectedly large number of non-oncology drugs selectively inhibited subsets of cancer cell lines in a manner predictable from the cell lines' molecular features. Our findings include compounds that killed by inducing PDE3A-SLFN12 complex formation; vanadium-containing compounds whose killing depended on the sulfate transporter SLC26A2; the alcohol dependence drug disulfiram, which killed cells with low expression of metallothioneins; and the anti-inflammatory drug tepoxalin, which killed via the multi-drug resistance protein ABCB1. The PRISM drug repurposing resource (https://depmap.org/repurposing) is a starting point to develop new oncology therapeutics, and more rarely, for potential direct clinical translation.

Trainee Thoracic Surgery Social Media Network: Early Experience With TweetChat-Based Journal Clubs.

BACKGROUND: Virtual journal clubs on Twitter (TweetChats) provide a platform to globally discuss publications. The Thoracic Surgery Social Media Network (TSSMN) is an organization that focuses on bringing social media attention to key publications in cardiothoracic surgery. TSSMN recently formed a Trainee Group with the goal of conducting chats covering key topics in cardiothoracic surgical training. The aim of this study was to characterize the pilot experience of this group. METHODS: The TSSMN trainee group held 3 TweetChats during the study period between 2017 and 2018. Each TweetChat was a structured discussion of 2 to 4 publications. The number of tweets, participants, most popular tweets, and impressions was assessed for each of the TweetChats. RESULTS: The 3 TweetChats had a mean of 40 participants (range, 36-45), generating an average of 497 tweets (range, 451-526) with a mean of 809,746 impressions (range, 591,814-1,140,000). Fruitful discussions on the topics of simulation in surgery, assessment of resident autonomy, and development of optimal organizational cultures to maximize team performance were held. CONCLUSIONS: Twitter is a useful tool to collaborate and disseminate information. The 3 TweetChats organized by TSSMN trainee delegates generated approximately 1500 tweets with 2 million impressions. By these metrics, the feasibility of a trainee-led TSSMN TweetChat was confirmed.

Factors Associated With New Persistent Opioid Usage After Lung Resection.

BACKGROUND: Opioid dependence, misuse, and abuse in the United States continue to rise. Prior studies indicate an important risk factor for persistent opioid use includes elective surgical procedures, though the probability following thoracic procedures remains unknown. We analyzed the incidence and factors associated with new persistent opioid use after lung resection. METHODS: We evaluated data from opioid-naïve cancer patients undergoing lung resection between 2010 and 2014 using insurance claims from the Truven Health MarketScan Databases. New persistent opioid usage was defined as continued opioid prescription fills between 90 and 180 days following surgery. Variables with a p value less than 0.10 by univariate analysis were included in a multivariable logistic regression performed for risk adjustment. Multivariable results were each reported with odds ratio (OR) and confidence interval (CI). RESULTS: A total of 3,026 patients (44.8% men, 55.2% women) were identified as opioid-naïve undergoing lung resection. Mean age was 64 ± 11 years and mean postoperative length of stay was 5.2 ± 3.3 days. A total of 6.5% underwent neoadjuvant therapy, while 21.7% underwent adjuvant therapy. Among opioid-naïve patients, 14% continued to fill opioid prescriptions following lung resection. Multivariable analysis showed that age less than or equal to 64 years (OR, 1.28; 95% CI, 1.03 to 1.59; p = 0.028), male sex (OR, 1.40; 95% CI, 1.13 to 1.73; p = 0.002), postoperative length of stay (OR, 1.32; 95% CI, 1.05 to 1.65; p = 0.016), thoracotomy (OR, 1.58; 95% CI, 1.24 to 2.02; p < 0.001), and adjuvant therapy (OR, 2.19; 95% CI, 1.75 to 2.75; p < 0.001) were independent risk factors for persistent opioid usage. CONCLUSIONS: The greatest risk factors for persistent opioid use (14%) following lung resection were adjuvant therapy and thoracotomy. Future studies should focus on reducing excess prescribing, perioperative patient education, and safe opioid disposal.