Adjuvant melatonin for the prevention of recurrence and mortality following lung cancer resection (AMPLCaRe): A randomized placebo controlled clinical trial.

BACKGROUND: Despite curative intent resection in patients with non-small cell lung cancer (NSCLC), recurrence leading to mortality remains too common. Melatonin has shown promise for the treatment of patients with lung cancer; however, its effect following cancer resection has not been studied. We evaluated if melatonin taken after complete resection reduces lung cancer recurrence and mortality, or impacts quality of life (QOL), symptomatology or immune function. METHODS: Participants received melatonin (20 mg) or placebo nightly for one year following surgical resection of primary NSCLC. The primary outcome was two-year disease-free survival (DFS). Secondary outcomes included five-year DFS, adverse events, QOL, fatigue, sleep, depression, anxiety, pain, and biomarkers assessing for immune function/inflammation. This study is registered at https://clinicaltrials.gov NCT00668707. FINDINGS: 709 patients across eight centres were randomized to melatonin (n = 356) versus placebo (n = 353). At two years, melatonin showed a relative risk of 1·01 (95% CI 0·83-1·22), p = 0·94 for DFS. At five years, melatonin showed a hazard ratio of 0·97 (95% CI 0·86-1·09), p = 0·84 for DFS. When stratified by cancer stage (I/II and III/IV), a hazard reduction of 25% (HR 0·75, 95% CI 0·61-0·92, p = 0·005) in five-year DFS was seen for participants in the treatment arm with advanced cancer (stage III/IV). No meaningful differences were seen in any other outcomes. INTERPRETATION: Adjuvant melatonin following resection of NSCLC does not affect DFS for patients with resected early stage NSCLC, yet may increase DFS in patients with late stage disease. Further study is needed to confirm this positive result. No beneficial effects were seen in QOL, symptoms, or immune function. FUNDING: This study was funded by the Lotte and John Hecht Memorial Foundation and the Gateway for Cancer Research Foundation.

Comparison of autofluorescence and white-light bronchoscopies performed with the Evis Lucera Spectrum for the detection of bronchial cancers: a meta-analysis.

BACKGROUND: Many recent studies have reported that autofluorescence bronchoscopy (AFB) has a superior sensitivity and decreased specificity in the diagnosis of bronchial cancers when compared with white-light bronchoscopy (WLB). We specifically analyzed the diagnostic performances of autofluorescence imaging video bronchoscopy (AFI) performed with the Evis Lucera Spectrum from Olympus, which is a relatively novel approach in detecting and delineating bronchial cancers, and compared it to the older WLB method. METHODS: We searched the PubMed, Embase, Web of Science, and CNKI databases from inception to July 12th, 2018 for trials in which patients were diagnosed with lung cancer via concurrent or combined use of AFI and WLB. The included studies were required to have a histologic diagnosis as the gold standard comparison, and a sufficient amount of data was extracted to assess the diagnostic capacity. A 2×2 table was constructed, and the area under the receiver-operating characteristic curve (AUC) of AFI and WLB was estimated by using a stochastic model for diagnostic meta-analysis using STATA software. RESULTS: A total of 10 articles were eligible for the meta analysis, comprising 1,830 patients with complete data included in the analysis. AFI showed a superior sensitivity of 0.92 (95% CI, 0.88-0.95) over WLB's 0.70 (95% CI, 0.58-0.80) with P<0.01, and a comparable specificity of 0.67 (95% CI, 0.51-0.80) compared with WLB's 0.78 (95% CI, 0.68-0.86) with P=0.056. Egger's test P value (0.225) demonstrated that there was no publication bias. CONCLUSIONS: Our research showed that in the evaluation of bronchial cancers, AFI was superior to conventional WLB. With its higher sensitivity, AFI could be valuable for avoiding misdiagnosis.

Impact of surgical approach on perioperative and long-term outcomes following esophagectomy for esophageal cancer.

BACKGROUND: Surgical resection remains a critical component of esophageal cancer treatment with curative-intent. The aim of this study was to compare open (OE) to minimally invasive Ivor Lewis esophagectomy (MIE) with respect to perioperative and oncologic outcomes. METHODS: Retrospective single-institution review of MIE and OE patients operated between 2001 and 2015 was conducted. Univariable and multivariable models were created using Cox regression. The Kaplan-Meier method was used to compare oncologic outcomes. Propensity score matching was used to compare oncological outcomes in MIE and OE patients. RESULTS: Of 210 esophageal resection patients, 47% had OE (137/291) and 25% had MIE (73/291). The MIE and OE groups were comparable with respect to patient factors and operative details. Fewer OE patients received neoadjuvant chemoradiation. MIE was associated with improved lymph node yield, (MIE = 30 [IQR:22-39]; OE = 14 [IQR:7-19], p < 0.001), less intraoperative blood loss (MIE = 312 mL [100-400]; OE = 657 mL [350-700], p < 0.001), and shorter median length of stay (MIE = 10 days [IQR = 8-14]; OE = 14 days [IQR = 11-22] p < 0.01). The OE group had significantly more adverse events resulting in reoperation or intensive care unit admission (MIE = 21%; OE = 34%; p < 0.01). On multivariable analysis, age and positive resection margins were associated with decreased odds of survival. The number of lymph nodes retrieved, positive resection margins, and pathologic stage were significant predictors of disease-free survival. Analysis of 69 matched pairs showed equivalent median overall survival (MIE = 49 months [18-67]; OE = 29 months [17-69]; p = 0.26) and disease-free survival (MIE = 9 [6-22]; OE = 13 [6-22]; p = 0.45) between the two groups. CONCLUSIONS: Although long-term oncologic outcomes appear to be similar, MIE is associated with significantly less intraoperative blood loss, improved lymph node yield, less risk of severe postoperative adverse events, and shorter length of stay.

Randomized trial of digital versus analog pleural drainage in patients with or without a pulmonary air leak after lung resection.

OBJECTIVE: An unclear aspect of digital pleural drainage technology is whether it can benefit all lung resection patients or only those who have a postoperative air leak. The aim of this study was to evaluate the impact of digital pleural drainage on time to chest tube removal and length of hospitalization, taking into consideration postoperative air leak status. METHODS: A single-center, randomized, controlled, open-label, parallel-group trial was conducted. On postoperative day 1, stratification according to air leak status was performed by 2 independent, blinded observers. Patients were randomized to a water-sealed, pleural drainage device (analog) or to a digital device (digital). RESULTS: In both air leak groups (no air leak = 87; air leak = 85), patient factors and operative details were comparable. In the no air leak group, the difference in median chest tube drainage between analog and digital randomization arms was not statistically significant (3 days vs 2.9 days; P = .05). Median length of stay was also comparable in that group (analog = 4.3 days; digital = 4 days; P = .09). In patients with an air leak, similar findings were observed for chest tube duration (analog = 5.6 days; digital = 4.9 days; P = .11) and length of stay (analog = 6.2 days; digital = 6.2 days; P = .36). Chest tube clamping trials were significantly reduced in the digital arm of the air leak absent (0% vs 16%; P = .01) and air leak present groups (23% vs 50%; P = .01). CONCLUSIONS: Although digital devices decreased tube clamping trials, the impact on duration of chest tube drainage and hospital stay was not statistically significant, even after stratifying by postoperative air leak status.

Using Surgeon-Specific Outcome Reports and Positive Deviance for Continuous Quality Improvement.

BACKGROUND: Using the thoracic morbidity and mortality classification to document all postoperative adverse events between October 2012 and February 2014, we created surgeon-specific outcome reports (SSORs) to promote self-assessment and to implement a divisional continuous quality improvement (CQI) program, on the construct of positive deviance, to improve individual surgeon's clinical performance. METHODS: Mixed-methods study within a division of six thoracic surgeons, involving (1) development of real-time, Web-based, risk-adjusted SSORs; (2) implementation of CQI seminars (n = 6; September 2013 to June 2014) for evaluation of results, collegial discussion on quality improvement based on identification of positive outliers, and selection of quality indicators for future discussion; and (3) in-person interviews to identify facilitators and barriers to using SSORs and CQI. Interview transcripts were analyzed using thematic analysis. RESULTS: Interviews revealed enthusiastic support for SSORs as a means to improve patient care through awareness of personal outcomes with blinded divisional comparison for similar operations and diseases, and apply the learning objectives to continuous professional development and maintenance of certification. Perceived limitations of SSORs included difficulty measuring surgeon expertise, limited understanding of risk adjustment, resistance to change, and belief that knowledge of sensitive data could lead to punitive actions. All surgeons believed CQI seminars led to collegial discussions, whereas perceived limitations included quorum participation and failing to circle back on actionable items. CONCLUSIONS: Real-time performance feedback using SSORs can motivate surgeons to improve their practice, and CQI seminars offer the opportunity to review and interpret results and address issues in a supportive environment. Whether SSORs and CQI can lead to improvements in rates of postoperative adverse events is a matter of ongoing research.

Prognostic significance of a positive radial margin after esophageal cancer resection.

OBJECTIVE: The prognostic significance of an incomplete esophageal cancer resection due to a positive microscopic radial margin remains unclear. The aim of this study is to examine the relationship between radial margin status and oncologic outcomes. METHODS: We performed a retrospective review of esophageal cancer resections between 2004 and 2012. Radial margin status was defined according to the College of American Pathologists. Exclusion criteria were complete pathologic response (n = 12), positive proximal or distal margin (n = 11), R2 resection (n = 5), and carcinoma in situ (n = 2). RESULTS: Of 154 patients, 30 (19%) had a positive radial margin (RM+) and 124 (81%) had a complete resection (R0). The 2 groups were similar with respect to age, gender, proportion of squamous tumors, middle thoracic tumor location, rate of neoadjuvant chemoradiation and adjuvant radiation, transhiatal approach, number of examined lymph nodes, and length of proximal and distal margins. In patients with stage III, the locoregional recurrence-free interval was similar between groups; however, RM+ was associated with a 17-month decrease in the median time to distant recurrence (RM+ = 7 months [95% confidence interval, 4-14]; R0 = 24 months [median not reached]; P < .01). The median survival was also significantly decreased by 12 months in the RM+ group (RM+ = 13 months [95% confidence interval, 7-26]; R0 = 25 months [95% confidence interval, 20-30]; P = .04). CONCLUSIONS: An isolated, positive microscopic radial margin was associated with a greater risk for distant recurrence. There was no impact on locoregional disease control. The role of adjuvant, systemic therapy in patients with an isolated, microscopically RM+ merits further evaluation.

Surgical management of colorectal lung metastasis.

Colon cancer is a systemic disease in 19% of patients and metastasizes most frequently to the liver and the lung. Survival is enhanced with complete surgical resection of pulmonary metastases. Comprehensive restaging and verification of preoperative fitness must precede resection. The operative approach is dictated by the anatomic location of the metastases, whereas the extent of resection remains a balance between complete removal of metastatic deposits while preserving as much lung parenchyma as possible. The presence of metastatic involvement of hilar and mediastinal lymph nodes is ominous. Multidisciplinary care is highly recommended. An evidence-based algorithm for the identification assessment and treatment of patients with pulmonary metastases is proposed.

Complications of pulmonary resection: postpneumonectomy pulmonary edema and postpneumonectomy syndrome.

Bassed on the authors' review of the unusual variants of PPS and the body of published experience, a revision of the current classification scheme for PPS into a more comprehensive form is justified as follows: (1) by the nature of obstruction; and (2) by the time of onset. This classification encompasses early and late symptom onset, as well as considering both airway and vascular compression. This scheme argues in favor of an expanded cardiac work-up in addition to the measures outlined previously for airway assessment. Althought PPS remains a rare clinical entity, the refinement in the understanding of this condition and the evolution of treatment options have vastly improved patient outcomes. A careful evaluation of the patient must be done before embarking on treatment owing to the numerous etiologies for progressive dyspnea in the pneumonectomy patient.