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.

Long-term Symptom Control After Laparoscopic Heller Myotomy and Dor Fundoplication for Achalasia.

BACKGROUND: Achalasia is a primary esophageal motility disorder in which there is incomplete relaxation of the lower esophageal sphincter and absence of peristalsis in the lower two thirds of the esophagus. A favored treatment is laparoscopic modified Heller myotomy with Dor fundoplication (LHMDor) with more than 90% immediate beneficial effect. The short-term outcomes of LHMDor are well documented, but stability and durability of postoperative symptom control over time is less understood. METHODS: Between 2004 and 2016, 54 patients with achalasia underwent LHMDor (single center). Using validated questionnaires, patients rated their symptoms in five domains: pain, gastroesophageal reflux disease (GERD), dysphagia, regurgitation, and quality of life. Symptom ratings were done preoperatively, 4 weeks postoperatively, 6 months postoperatively, and yearly after the operation. RESULTS: As expected, patients reported marked improvement in dysphagia, odynophagia, regurgitation, GERD, and quality of life after the operation (P < .001). From then on, the symptom control remained durable with respect to absence of pain, regurgitation, and odynophagia; however, we observed a recurrence of GERD symptoms beginning 3 to 5 years postoperatively (P = .001 and P = .04, respectively), with associated increased antireflux medication use. After initial LHMDor, 5 patients required endoscopic dilatation an average of 1.5 years postoperatively, and no patient required reoperation. Patients reported preserved improved quality of life to 11 years after the operation (P = .001). CONCLUSIONS: These results demonstrate the durability of LHMDor in the definitive management of achalasia, offering consistent symptomatic relief and significant improvement in quality of life over the decade after surgery, despite some increase in GERD symptoms and antireflux medication use.

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.

Measuring surgical quality: comparison of postoperative adverse events with the american college of surgeons NSQIP and the Thoracic Morbidity and Mortality classification system.

BACKGROUND: Monitoring surgical outcomes is critical to quality improvement; however, different data-collection methodologies can provide divergent evaluations of surgical outcomes. We compared postoperative adverse event reporting on the same patients using 2 classification systems: the retrospectively recorded American College of Surgeons (ACS) NSQIP and the prospectively collected Thoracic Morbidity and Mortality (TM&M) system. STUDY DESIGN: Using the TM&M system, complications and deaths were documented daily by fellows and reviewed weekly by staff for all thoracic surgical cases conducted at our institution (April 1, 2010 to December 31, 2011). The ACS NSQIP recording was performed 30 to 120 days after index surgery by trained surgical clinical reviewers on a systemic sampling of major cases during the same time period. Univariate analyses of the data were performed. RESULTS: During the study period, 1,788 thoracic procedures were performed (1,091 were designated "major," as per ACS NSQIP inclusion criteria). The ACS NSQIP evaluated 182 of these procedures, representing 21.1% and 16.7% of patients and procedures, respectively. Mortality rates were 1.4% in TM&M vs 2.2% in ACS NSQIP (p = 0.42). Total patients and procedures with complications reported were 24.4% and 31.1% by TM&M vs 20.2% and 39.0% by ACS NSQIP (p = 0.23 and 0.03), respectively. Rates of reported cardiac complications were higher in TM&M vs ACS NSQIP (5.8% vs 1.1%; p = 0.01), and wound complications were lower (2.5% vs 6.0%; p = 0.01). CONCLUSIONS: Although overall rates were similar, significant differences in collection, definitions, and classification of postoperative adverse events were observed when comparing TM&M and ACS NSQIP. Although both systems offer complementary value, harmonization of definitions and severity classification would enhance quality-improvement programs.

Incidence, severity and perioperative risk factors for atrial fibrillation following pulmonary resection.

OBJECTIVES: Postoperative atrial fibrillation (PAF) occurs commonly following pulmonary resection. Our aims were to quantify the incidence and severity of PAF using the Thoracic Morbidity & Mortality classification system, and identify risk factors for PAF. METHODS: All consecutive patients undergoing pulmonary resection at a single centre (January 2008 - April 2010) were enrolled. PAF was defined as postoperative, electrocardiographically documented and requiring initiation of pharmacological therapy. Univariate and multivariate analyses of risk factors associated with the development of PAF were conducted. RESULTS: The incidence of PAF was 11.8% (n = 43) of 363 pulmonary resections (open: n = 173; 47.7%; video-assisted: n = 177; 48.8%; converted: n = 13; 3.6%): sublobar (n = 93; 25.6%), lobectomy (n = 237; 65.3%), bilobectomy (n = 7; 1.9%) and pneumonectomy (n = 24; 6.6%). Twenty-eight cases (65.1%) were uncomplicated/transient, and 15 cases (34.9%) were complicated/persistent PAF, defined as lasting for >7 days (40.0%), requiring cardioversion (13.3%), vasopressors (33.3%), in-hospital use of anticoagulants (46.7%) and/or anticoagulants on discharge (26.7%). Patients with PAF had increased mean lengths of hospital stay (10.5 days vs 6.9 days; P = 0.04). Peak onset of PAF occurred 2.5 (standard deviation (SD) ± 1.3) days after pulmonary resection, lasting for 1.8 ± 2.8 (mean, ±SD) days. Multivariate analysis identified (relative risk; 95% confidence interval): age ≥70 years (2.3; 1.1-5.1), history of angioplasty/stents/angina (4.0; 1.4-11.3), thoracotomy (3.6; 1.4-9.3), conversion to open thoracotomy (16.5; 2.2-124.0) and extent of surgery/stage (7.1; 1.0-49.4) as predictors of PAF. CONCLUSIONS: While the majority of PAF is uncomplicated and transient, one-third of cases lead to persistence or major intervention. Age, coronary artery disease and extent of surgery/stage increase the risk of PAF following pulmonary resection. Identifying patients with elevated risk may lead to targeted prophylaxis to reduce the incidence of PAF.

Quantifying the incidence and impact of postoperative prolonged alveolar air leak after pulmonary resection.

OBJECTIVE: Prolonged alveolar air leak (PAAL) is a frequent occurrence after lobectomy or lesser resections. The resulting complications and their impact are not well understood. Our aims are to prospectively determine the incidence and severity of PAAL after pulmonary resection using the Thoracic Morbidity & Mortality classification system and to identify risk factors. METHODS: A prospective collection of Thoracic Morbidity & Mortality data was performed for all consecutive pulmonary resections (n = 380; January 2008 to April 2010). Demographics, comorbidities, and preoperative cardiopulmonary assessment were retrospectively identified. The incidence and severity (grades I-V) of burden from PAAL were quantified using the Ottawa Thoracic Morbidity & Mortality system. Risk factors for PAAL and severe PAAL (defined as leading to major intervention, organ failure, or death) were sought with univariate and multivariate analyses. RESULTS: The incidences of PAAL and severe PAAL were 18% and 4.8%, respectively. PAAL prolonged the median hospital stay by 4 days. The majority of complications associated with PAAL were limited to pulmonary and pleural categories (90%). Significant predictors of PAAL from multivariate analysis include severe radiologic emphysema (odds ratio [OR], 2.8; confidence interval [CI], 1.2-6.2), histopathologic emphysema (OR, 1.9; CI, 1.1-3.6), percentage of predicted value for forced expiratory volume in 1 second less than 80% (OR, 1.9; CI, 1.1-3.3), and lobectomy (OR, 4.9; CI, 1.-14.1). Risk factors for severe PAAL include radiologic emphysema, percentage of predicted value for forced expiratory volume in 1 second less than 80%, forced expiratory volume in 1 second/forced vital capacity ratio less than 70%, and intraoperative difficulties (P < .05). CONCLUSIONS: PAAL leads to longer hospital stays, and approximately 4.8% of patients undergoing pulmonary resection experience PAAL that necessitates placement of additional chest drains, bronchoscopy, reoperation, or life support. Further study is required to assess the cost-effectiveness of measures to reduce PAAL.

Assessing the status of thoracic surgical research and quality improvement programs: a survey of the members of the Canadian Association of Thoracic Surgeons.

OBJECTIVES: Assessing the degree of involvement and participation in thoracic surgical research as well as surgical quality improvement conducted across Canadian institutions is difficult as no common data collection system and no prior studies exist. As a pilot investigation, we designed and conducted a membership survey of the Canadian Association of Thoracic Surgeons (CATS) to evaluate the extent of participation in research and quality improvement processes among thoracic surgeons. DESIGN, SETTING, AND PARTICIPANTS: A 45-item needs assessment survey was mailed to all national members of CATS (n = 86) in August 2009. Questions primarily focused on clinical research programs and research activity, research funding, database use and interest, and other methods of quality monitoring. RESULTS: The 49 completed surveys represented a 57.0% response rate and 28 institutions across Canada. Research in basic and clinical science is conducted by 17.0% and 80.9% of the respondents, respectively. The annual budget of research funds is most commonly between $5000 and $50,000. A total of 72.0% (n = 18) of institutions do not have a formal surgery quality assessment program and 92.3% (n = 24) do not participate in a national or international thoracic surgery database. Ten institutions (38.6%) have a local thoracic surgery database for quality monitoring. Other systems of monitoring surgical quality include formal morbidity and mortality rounds (69.2%; n = 8 institutions), formal evaluation of surgical wait times (73.1%; n = 19 institutions), and patient satisfaction surveys (71.4%; n = 10 institutions). Overall, 97.8% of surgeons would be willing to share data on morbidity and mortality with other centers, and 73.1% have a high or very high level of interest in participating in a national thoracic surgery quality database. CONCLUSIONS: A high level of interest and participation exists in thoracic surgery research. However, more robust quality improvement processes are needed for thoracic surgical oncology services. A national thoracic surgery quality improvement database offers a potential means to improve practice effectiveness, standardize surgical outcomes, and promote thoracic research across Canada.

Evaluating the reliability and reproducibility of the Ottawa Thoracic Morbidity and Mortality classification system.

BACKGROUND: Minimizing adverse events after surgery is widely recognized as an important indicator of quality; yet no consensus has been reached on how to standardize the reporting of adverse events after surgical procedures. Our objectives were to develop a standardized classification system to monitor both the presence and severity of thoracic morbidity and mortality, and to evaluate its reliability and reproducibility among a national cohort of thoracic surgeons. METHODS: To assess the Thoracic Morbidity and Mortality classification system (based on the Clavien-Dindo classification of adverse events), a 31-item questionnaire was sent to all members of the Canadian Association of Thoracic Surgeons in August 2009, consisting of a general description of the Thoracic Morbidity and Mortality severity grades, 20 case-based questions of postoperative adverse events to be classified, and questions regarding personal judgments. We derived descriptive and quantitative information using weighted Kappa statistics. RESULTS: Fifty-two (54.7%) thoracic surgeons completed the questionnaire; 41 (78.8%) of the respondents were affiliated with an academic teaching hospital. A total of 1,326 individual weighted Kappa statistics were calculated for all distinct pairs of raters, of which 1,152 (87%) were greater than 0.81, a range that is interpreted as "almost perfect agreement." A further 174 (13%) were in the range between 0.61 and 0.8, interpreted as "substantial agreement." All results were statistically significant (p < 0.0001). The classification system was regarded as straightforward (98% of the respondents), reproducible (94%), logical (92%), and useful (98%). CONCLUSIONS: The modified classification system appears to offer objective, reliable, and reproducible reporting of thoracic morbidity and mortality, and thus may assist continuous quality improvement in thoracic surgery.

Systematic classification of morbidity and mortality after thoracic surgery.

BACKGROUND: Objective reporting of postoperative complications is the foundation of surgical quality assurance. We developed a system to identify both presence and severity of thoracic morbidity and mortality, and evaluated its feasibility and utility over the first two years of its implementation. METHODS: The system was based on the Clavien-Dindo classification, in which the severity of a complication is proportional to the effort to treat it. Definitions were developed by peer review and questionnaire. All patients undergoing thoracic surgery (January 2008 to December 2009) were prospectively evaluated. RESULTS: A total of 953 patients (mean age 61 years; range, 14 to 95) underwent thoracic surgery (total # cases 1260), of which 369 patients had at least one complication (29.3% procedures). Grades I and II include minor complications requiring no therapy or pharmacologic intervention only. Grades III and IV are major complications that require surgical intervention or life support. Grade V complications result in patient death. Grades I, II, III, and IV complications comprised 4.9%, 63.9%, 21.1%, and 7.8% of all complications; overall mortality rate (grade V) was 2.2%. The most common complications were prolonged air leak (18.8%) and atrial fibrillation (18.2%) after pulmonary resection, and atrial fibrillation (11.5%) after esophagectomy-gastrectomy. Prolonged air leak led to a major complication (13%), readmission (17%), or prolonged hospital stay (29%) to a greater extent than atrial fibrillation (3%, 2%, and 7%, respectively). CONCLUSIONS: This standardized classification system for identifying presence and severity of thoracic surgical complications is feasible, facilitates objective comparison, identifies burden of illness of individual complications, and provides an effective method for continuous surgical quality assessment.

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.

Giant hiatal hernia with gastric volvulus complicating pneumonectomy.

Gastric volvulus is a potentially lethal condition. Pneumonectomy patients have decreased physiologic reserve, and thus they are more susceptible to morbidity and mortality from postoperative complications. We report successful management of a patient with hiatal hernia that resulted in acute gastric volvulus after left pneumonectomy.

The Ross procedure in adults: intermediate-term results.

BACKGROUND: The durability of the Ross procedure may be optimized by appropriate geometric matching of the aortic and pulmonary artery roots. We employed a surgical strategy to standardize the operation in order to avoid more readily a geometric mismatch. METHODS: The Ross procedure was performed as a root replacement. Without regard for patient body surface area, the aortic annulus was plicated to 23 mm and externally buttressed with felt. Geometric mismatch of the distal autograft anastomosis was avoided by liberal use of a synthetic interposition graft, and the anastomosis was also externally buttressed with felt. An over-sized pulmonary homograft (27 to 28 mm) was routinely used to reconstruct the right ventricular outflow tract. RESULTS: Forty-four consecutive patients (27 men and 17 women; mean age, 49 +/- 9 years) were operated on between January 1997 and March 2002. Mean follow-up was 38 +/- 5 months. Twenty-nine patients had aortic stenosis and 15 had aortic regurgitation. Aortic annular plication was done in 41 (93%) and an aortic interposition was used in 14 (32%). There were three hospital deaths, with no subsequent deaths. Only 1 patient required reoperation 2.5 years postoperatively from recurrent endocarditis. No patient has more that "trivial" autograft insufficiency, and the mean autograft gradient was 7 +/- 3 mm Hg. No patient has significant pulmonary homograft stenosis. CONCLUSIONS: Geometric matching of the aortic and pulmonary roots may be readily accomplished using a standardized approach to the Ross procedure. In turn, this may optimize the durability of the operation.

McKeown esophagogastrectomy for esophageal carcinoma after free jejunal graft.

Several well-described options exist for reconstruction after total esophagectomy for esophageal carcinoma. We present the case of a patient who was treated for squamous cell carcinoma of the esophagus; the patient had undergone treatment with neoadjuvant chemoradiation and free jejunal transfer for a cervical esophageal tumor 13 years earlier. Through a three-field approach, esophagectomy and reconstruction with a cervical gastrojejunal anastomosis were performed.