How Much Delay Matters? How Time to Treatment Impacts Overall Survival in Early Stage Lung Cancer.

OBJECTIVES: The aim of this study was to identify drivers of time from diagnosis to treatment (TTT) of surgically resected early stage non-small cell lung cancer (NSCLC) and determine the effect of TTT on post-resection survival. SUMMARY BACKGROUND DATA: Large database studies that lack relevant comorbidity data have identified longer TTT asa driver of worse overall survival. METHODS: From January 1, 2014 to April 1, 2018, 599 patients underwent lung resection for clinical stage I and II NSCLC. Random forest classification, regression, and survival were used to estimate likelihood of TTT = 0 (tissue diagnosis obtained at surgery), >0 (diagnosis obtained pre-resection), and effect of TTT on all-cause mortality. RESULTS: Patients with TTT > 0 (n = 413) had median TTT of 42 days (25-75 th percentile: 27-59 days). Patients with TTT = 0 (n = 186) had smaller tumors and higher percent predicted forced expiratory volume in 1 second (FEV 1 %). Patients with history of stroke, oncology consultation, invasive mediastinal staging, low and high extremes of FEV 1 % had longer TTT. Higher clinical stage, lack of preoperative stress test, anemia, older age, lower FEV1% and diffusion lung capacity, larger tumor size, and longer TTT were the most important predictors of all-cause mortality. One- and 5-year overall survival decreased when TTT was >50 days. CONCLUSIONS: Preoperative physiologic workup and multidisciplinary evaluation were the predominant drivers of longer TTT. Patients with TTT = 0have more favorable presentation and should be considered in TTT analyses for early stage lung cancer populations. The time needed to clinically stage and optimize patients for resection is not deleterious to overall survival until resection is performed after 50 days from diagnosis.

Quantifying the subjective: length-to-height ratio characterizes achalasia esophageal tortuosity.

BACKGROUND: Esophageal morphology in achalasia is thought to affect outcomes, with "end-stage" sigmoidal morphology faring poorly; however, evaluation of morphology's role in outcomes has been limited by lack of objective characterization. Hence, the goals of this study were twofold: characterize the variability of timed barium esophagram (TBE) interpretation and evaluate an objective classification of TBE tortuosity: length-to-height ratio (LHR). We hypothesized that the esophagus must elongate to become sigmoidal such that sigmoidal morphology would demonstrate a larger LHR. METHODS: Ninety pre-operative TBEs were selected from an institutional database. Esophageal morphology was categorized as straight, intermediate, or sigmoidal. Esophageal length was measured by a mid-lumen line from the aortic knob to the esophagogastric junction on TBE; height was measured vertically from the aortic knob to the level of the esophagogastric junction. The length divided by the height generated the LHR. Descriptive statistics and frequency of expert agreement were calculated. Median LHR was compared between consensus morphologies. A receiver operating characteristic (ROC) determined the optimal LHR for sigmoidal vs non-sigmoidal characterization. RESULTS: From a total of 90 pre-operative TBEs, expert consensus morphology was reached in 56 (62.2%) cases. Pairs of experts agreed on morphology in 62-74% of TBEs, with all three experts agreeing on 46.7-48.9% of cases. Median LHR between expert consensus morphologies was 1.03, 1.09, and 1.24 for straight, intermediate, and sigmoidal morphologies, respectively (p < 0.001). ROC demonstrated that an LHR cutoff of 1.13 was 100% sensitive and 95% specific (AUC 0.99) for ruling out sigmoidal morphology. CONCLUSION: These findings confirm our anecdotal experience that subjective morphology interpretation is variable, even between experts at a high-volume center. LHR provides an objective method for classification, allowing us to overcome the limitations of inter-observer variability, thus paving the way for future study of the role of morphology in achalasia outcomes.

Survival and recurrence patterns after neoadjuvant docetaxel, cisplatin, and 5-fluorouracil (DCF) for locally advanced esophagogastric adenocarcinoma.

INTRODUCTION: We have previously identified Docetaxel, Cisplatin, and 5FU (DCF) as a safe, tolerable, and effective regimen in the neoadjuvant setting for locally advanced adenocarcinoma (ADC) of the esophagus and esophagogastric junction (EGJ). We hypothesized that DCF combined with enhanced surgical control would result in a low rate of local or regional recurrence, and thus reviewed our outcomes with this treatment regimen. METHODS: A prospectively entered database of all esophageal and EGJ ADC patients resected at a high-volume referral center over 6 years (9/07-9/13) was reviewed for cases treated with curative intent neoadjuvant DCF followed by en bloc resection with extended lymphadenectomy (D2/D3). Recurrences was defined as locoregional (biopsy on endoscopy/regional lymph nodes (LNs)) and distant. Standard statistical techniques were used. RESULTS: Of 279 patients with ADC, 86 (85% male, mean age 63 years (interquartile range 56-70)) underwent preoperative DCF and curative intent resection for locally advanced ADC (cT3 93%; cN+ 69%) of the EGJ (54%) or distal esophagus (46%). After median follow-up of 40 months, the overall 5-year survival was 54% and 43 (52%) had recurred at a median time of 14 months. Sites of recurrence included locoregional only in 2 of 45 (4%), distant only in 40 of 45 (89%), and locoregional and distant in 3 of 45 (7%). DISCUSSION: The present study demonstrates favourable oncologic outcomes with low local/regional recurrence and an excellent overall 5-year survival after neoadjuvant DCF for esophageal and EGJ ADCs. Because the majority of recurrences were distant, our data support the notion that efforts to improve outcomes in these patients should concentrate on enhancing systemic, rather than local, therapy.

Predictors of mortality and morbidity for acute care surgery patients.

BACKGROUND: As the implementation of exclusive acute care surgery (ACS) services thrives, prognostication for mortality and morbidity will be important to complement clinical management of these diverse and complex patients. Our objective is to investigate prognostic risk factors from patient level characteristics and clinical presentation to predict outcomes including mortality, postoperative complications, intensive care unit (ICU) admission and prolonged duration of hospital stay. METHODS: Retrospective review of all emergency general surgery admissions over a 1-year period at a large teaching hospital was conducted. Factors collected included history of present illness, physical exam and laboratory parameters at presentation. Univariate analysis was performed to examine the relationship between each variable and our outcomes with chi-square for categorical variables and the Wilcoxon rank-sum statistic for continuous variables. Multivariate analysis was performed using backward stepwise logistic regression to evaluate for independent predictors. RESULTS: A total of 527 ACS admissions were identified with 8.1% requiring ICU stay and an overall crude mortality rate of 3.04%. Operative management was required in 258 patients with 22% having postoperative complications. Use of anti-coagulants, systolic blood pressure <90, hypothermia and leukopenia were independent predictors of in-hospital mortality. Leukopenia, smoking and tachycardia at presentation were also prognostic for the development of postoperative complications. For ICU admission, use of anti-coagulants, leukopenia, leukocytosis and tachypnea at presentation were all independent predictive factors. A prolonged length of stay was associated with increasing age, higher American Society of Anesthesiologists class, tachycardia and presence of complications on multivariate analysis. CONCLUSIONS: Factors present at initial presentation can be used to predict morbidity and mortality in ACS patients.

Educating medical trainees on medication reconciliation: a systematic review.

BACKGROUND: Effective medication reconciliation is critical in reducing the risk of preventable adverse drug events. Medical trainees are often responsible for medication reconciliation on admission, transfer and discharge of the most vulnerable patients; therefore, it is important that trainees are educated on this aspect of quality care. METHODS: We conducted a systematic review using MEDLINE and EMBASE databases to identify education initiatives targeted at improving trainee skill and knowledge in carrying out medication reconciliation. Studies published in English or French between July 1980 and July 2013, where the primary focus of the article was the role of medical trainees in conducting medication reconciliation, and where trainee-specific data was reported, were included. Included articles must have reported trainee-specific data. Given the anticipated heterogeneity and array of outcomes, we were unable to employ a specific tool in assessing the risk of bias across studies. RESULTS: Seven studies met pre-specified eligibility criteria, indicating the lack of published education initiatives targeted towards improving trainee knowledge and experience. Four described an education intervention targeted towards students completing internal medicine clerkship, while the remaining 3 were implemented among residents. Although no two interventions were the same, 5 out of 7 included an experiential component. CONCLUSIONS: Varying success was achieved with medication reconciliation education interventions. While some noted improved competence and/or confidence amongst trainees, namely undergraduate medical students, others noted little effect resulting from the intervention.

Predictive value of negative initial postoperative imaging after endovascular aortic aneurysm repair.

OBJECTIVE: The risk of endoleak and reintervention after endovascular abdominal aortic aneurysm repair necessitates lifelong surveillance, which has associated costs, radiation exposure, and risk of nephrotoxicity. The best imaging method and timing of surveillance remain controversial. We sought to determine if a negative result of first postoperative imaging by computed tomography (CT) scan was predictive of decreased need for reintervention. We hypothesized that initial negative postoperative imaging could identify a low-risk cohort of patients who could be observed less frequently. METHODS: Retrospective review of prospectively collected institutional outcomes data (2004-2009) included stratification according to postoperative imaging results. Baseline characteristics and aneurysm morphology were compared between the two groups. Cox regression analysis was used to identify risk factors predictive for endoleak-related reintervention. Kaplan-Meier survival curves were used to plot freedom from all-cause reintervention and endoleak-related reintervention for the two groups. RESULTS: A total of 134 patients were included in the analysis. A total of 107 patients (80%) had negative initial postoperative imaging, whereas 27 patients (20%) had evidence of an endoleak. There were no significant differences between the two groups in terms of comorbidities or anticoagulation status. Kaplan-Meier survival curves showed that there was a significant difference between those patients who had a negative initial CT scan and those who had a positive scan for endoleak in terms of both overall reintervention rates and leak-related reintervention rates. Endoleak on the first postoperative CT scan was associated with a hazard ratio of 6.37 (confidence interval, 2.02-20.10; P = .002) for leak-related reintervention and a hazard ratio of 6.01 (confidence interval, 2.24-16.17; P < .001) for all-cause reintervention. CONCLUSIONS: Patients with negative initial postoperative imaging were significantly less likely to require repeated interventions. These data suggest that these patients are candidates for less rigorous screening protocols.

Surgical Diaphragm: Anatomy and Physiology.

The diaphragm is a musculoaponeurotic structure separating the thoracic and abdominal cavities. It plays important roles in both respiration and maintaining gastrointestinal function. A careful consideration of anatomy should be taken during surgical procedures to minimize injury to this crucial organ.

The Value of Fundoplication in the Treatment of Type I Achalasia.

BACKGROUND: Type I achalasia comprises 20% of achalasia and has nearly absent esophageal motor activity. Concerns that fundoplication decreases the effectiveness of Heller myotomy in these patients has increased adoption of peroral endoscopic myotomy (POEM). Hence, we compared outcomes after Heller myotomy with Dor fundoplication vs POEM. METHODS: From 2005 to 2020, 150 patients with type I achalasia underwent primary surgical myotomy (117 Heller myotomy, 33 POEM). Patient demographics, prior treatments, timed barium esophagrams, Eckardt scores, and reinterventions were assessed between the 2 groups. Median follow-up was 5 years for Heller myotomy and 2.5 years for POEM. RESULTS: The Heller myotomy group was younger, had fewer comorbidities, and lower body mass index vs POEM. Risk-adjusted models demonstrated clinical success (Eckardt ≤3) in 83% of Heller myotomies and 87% of POEMs at 3 years; longitudinal complete timed barium esophagram emptying and reintervention were also similar. An abnormal pH test result was documented in 10% (6 of 60) after Heller myotomy and in 45% (10 of 22) after POEM (P < .001). CONCLUSIONS: Despite nearly absent esophageal contractility, Heller myotomy with Dor fundoplication and POEM result in similar long-term symptom relief, esophageal emptying, and occurrence of reintervention in patients with type I achalasia. There is decreased esophageal acid exposure with the addition of a fundoplication, without compromised esophageal drainage, allaying fears of a detrimental effect of a fundoplication. Hence, choice of procedure may be personalized based on patient characteristics and esophageal morphology and not solely on manometric subtype.

Paraconduit hernia following esophagectomy: Is it safe to watch and wait?

OBJECTIVES: We hypothesized that emergency complications related to asymptomatic paraconduit hernias may occur less often than generally believed. Therefore, we assessed the occurrence and timing of paraconduit hernia diagnosis after esophagectomy, as well as outcomes of these asymptomatic patients managed with a watch-and-wait approach. METHODS: From 2006 to 2021, 1214 patients underwent esophagectomy with reconstruction at the Cleveland Clinic. Among these patients, computed tomography scans were reviewed to identify paraconduit hernias. Medical records were reviewed for timing of hernia diagnosis, hernia characteristics, and patient symptoms, complications, and management. During this period, patients with asymptomatic paraconduit hernias were typically managed nonoperatively. RESULTS: Paraconduit hernias were identified in 37 patients. Of these, 31 (84%) had a pre-esophagectomy hiatal hernia. Twenty-one hernias (57%) contained colon, 7 hernias (19%) contained pancreas, and 9 hernias (24%) contained multiple organs. Estimated prevalence of paraconduit hernia was 3.3% at 3 years and 7.7% at 10 years. Seven patients (19%) had symptoms, 4 of whom were repaired electively, with 2 currently awaiting repairs. No patient with a paraconduit hernia experienced an acute complication that required emergency intervention. CONCLUSIONS: The risk of paraconduit hernia increases with time, suggesting that long-term symptom surveillance is reasonable. Emergency complications as a result of asymptomatic paraconduit hernias are rare. A small number of patients will experience hernia-related symptoms, sometimes years after hernia diagnosis. Our findings suggest that observation of asymptomatic paraconduit hernias (watch and wait) may be considered, with repair considered electively in patients with persistent symptoms.

Development and validation of a universal esophageal patient-reported outcome measure: The Cleveland Clinic Esophageal Questionnaire (CEQ).

OBJECTIVE: Currently, there is no validated patient-reported outcome measure (PROM) applicable to all esophageal diseases. Our objective was to create a psychometrically robust, validated universal esophageal PROM that can also objectively assess patients' quality of life (QoL). METHODS: The pilot PROM constructed based on expert opinions, literature review, and previous unpublished institutional research had 27 items covering 8 domains. It was completed by 30 patients in the outpatient clinic followed by a structured debriefing interview, which allowed for refining the PROM. The final PROM: Cleveland Clinic Esophageal Questionnaire (CEQ) included 34 items across 6 domains (Dysphagia, Eating, Pain, Reflux & Regurgitation, Dyspepsia, Dumping), each accompanied by a corresponding QoL component. Further psychometric assessment of the PROM was conducted by evaluating (1) acceptability, (2) construct validity, (3) reliability, and (4) responsiveness. RESULTS: Five hundred forty-six unique patients (median 63.7 years [54.3-71.7], 53% male [287], 86% White) completed CEQ at >90% completion within 5 minutes. Construct validity was demonstrated by differentiating scores across esophageal cancer (n = 146), achalasia (n = 170), hiatal hernia (n = 160), and other diagnoses (n = 70). Internal reliability (Cronbach alpha 0.83-0.89), and test-retest reliability (intraclass correlation coefficients 0.63-0.85) were strong. Responsiveness was demonstrated through CEQ domains improving for 53 patients who underwent surgery for achalasia or hiatal hernia (Cohen d 0.86-2.59). CONCLUSIONS: We have constructed a psychometrically robust, universal esophageal PROM that allows concise, consistent, objective quantification of symptoms and their effect on the patient. The CEQ is valuable in prognostication and tracking of longitudinal outcomes in both benign and malignant esophageal diseases.

Multi-institutional beta testing of a novel cervical esophagogastric anastomosis simulator.

Objective: A novel simulator developed to offer hands-on practice for the stapled side-to-side cervical esophagogastric anastomosis was tested previously in a single-center study that supported its value in surgical education. This multi-institutional trial was undertaken to evaluate validity evidence from 6 independent thoracic surgery residency programs. Methods: After a virtual session for simulation leaders, learners viewed a narrated video of the procedure and then alternated as surgeon or first assistant. Using an online survey, perceived value was measured across fidelity domains: physical attributes, realism of materials, realism of experience, value, and relevance. Objective assessment included time, number of sutures tearing, bubble test, and direct inspection. Comparison across programs was performed using the Kruskal-Wallis test. Results: Surveys were completed by 63 participants as surgeons (17 junior and 20 senior residents, 18 fellows, and 8 faculty). For 3 of 5 tasks, mean ratings of 4.35 to 4.44 correlated with "somewhat easy" to "very easy" to perform. The interrupted outer layer of the anastomosis rated lowest, suggesting this task was the most difficult. The simulator was rated as a highly valuable training tool. For the objective measurements of performance, "direct inspection" rated highest followed by "time." A total of 90.5% of participants rated the simulator as ready for use with only minor improvements. Conclusions: Results from this multi-institutional study suggest the cervical esophagogastric anastomosis simulator is a useful adjunct for training and assessment. Further research is needed to determine its value in assessing competence for independent operating and associations between improved measured performance and clinical outcomes.

Clinical T2 N0 M0 Esophageal Cancer: Identifying Predictive Factors of Upstaging.

BACKGROUND: Inaccuracy of clinical staging renders management of clinical T2 N0 M0 (cT2 N0 M0) esophageal cancer difficult. When an underlying advanced-stage disease is understaged to cT2 N0 M0, patients miss the opportunity to gain the potential benefits of neoadjuvant therapy. This study aimed to identify preoperative factors that predict underlying advanced-stage esophageal cancer. METHODS: From 2000 to 2020, 1579 patients with esophageal cancer underwent esophagectomy. Sixty patients who underwent upfront surgery for cT2 N0 M0 esophageal cancer were included in this study. The median age was 62.5 years, and 78% (n = 47) of these patients were male. Radiologic, clinical, and endoscopic factors were evaluated as preoperative markers. The Fisher exact and the Wilcoxon rank sum tests were used for categoric and continuous variables, respectively. Random forest classification was used to identify preoperative factors for predicting upstaging and downstaging. RESULTS: Of the 60 patients, 8 (13%) were found to have pathologic T2 N0 M0 esophageal cancer. Sixteen (27%) patients had cancer that was pathologically downstaged, and 36 (60%) had upstaged disease. Seven (19%) patients had upstaged cancer on the basis of the pathologic T stage, 14 (39%) had upstaging on the basis of the pathologic N stage, and 15 (42%) had upstaging on the basis of both T and N stages. Dysphagia (P = .003) and tumor maximum standardized uptake value (P = .048) were predictors of upstaging, with a combined predictive value of up to 75%. CONCLUSIONS: The presence of dysphagia and of high maximum standardized uptake value (≥5) of the tumor is predictive of more advanced underlying disease for patients with cT2 N0 M0 esophageal cancer, and these patients should be considered for neoadjuvant therapy.

Cost-effectiveness of minimally invasive versus open esophagectomy for esophageal cancer.

BACKGROUND: A recent randomized trial comparing minimally invasive (MIE) and open esophagectomy for esophageal cancer reported improved short-term outcomes. However, MIE has increased operative costs, and it is unclear whether the short-term benefits of MIE outweigh the increased operative costs. Therefore, the objective of this study was to determine the cost-effectiveness of MIE compared to open esophagectomy for esophageal cancer. METHODS: A decision-analysis model was developed to estimate the expected costs and outcomes after MIE and open esophagectomy from a health care system perspective with a time horizon of 1 year. Costs were represented in 2012 Canadian dollars, and effectiveness was measured in quality-adjusted life-years (QALYs). Probabilistic sensitivity analysis assessed parameter uncertainty. RESULTS: MIE was estimated to cost $1641 (95% confidence interval 1565, 1718) less than open esophagectomy, with an incremental gain of 0.022 QALYs (95% confidence interval 0.021, 0.023). MIE was therefore dominant over open esophagectomy. On deterministic sensitivity analyses, the results were most sensitive to variations in length of stay. Probabilistic sensitivity analysis demonstrated the robustness of the base case result, with 66, 77, and 82% probabilities of cost-effectiveness at willingness-to-pay thresholds of $0/QALY, $50,000/QALY, and $100,000/QALY, respectively. CONCLUSIONS: MIE is cost-effective compared to open esophagectomy in patients with resectable esophageal cancer.

Achalasia: Surgery Versus Per-Oral Endoscopic Myotomy.

Approaches to achalasia include non-operative and operative techniques with Heller Myotomy and Per-Oral Endoscopic Myotomy (POEM) at the forefront of palliative strategies. Given the diverse subtypes and the time-dependent failure pattern for achalasia, there is no standard approach. We elect for a POEM for type III achalasia, poor functional status, hostile abdomen, and salvage after the previous myotomy. A Heller myotomy is elected over a POEM for type II achalasia, presence of diverticulum, and hiatal hernia. As long-term outcomes become available, an optimal customized strategy will become clearer.

Preoperative predictors of spread through air spaces in lung cancer.

OBJECTIVE: Spread through air spaces (STAS) is a new histologic feature of invasion of non-small cell lung cancer that lacks sensitivity and specificity on frozen sections and is associated with higher recurrence and worse survival with sublobar resections. Our objective is to identify preoperative characteristics that are predictive of STAS to guide operative decisions. METHODS: From January 2018 through December 2021, 439 cT1-3N0 M0 patients with non-small cell lung cancer and a median age of 68 years, 255 (58%) women, who underwent primary surgery at our institution were included. Patients who received neoadjuvant therapy and whose STAS status was not documented were excluded. Age, sex, smoking status, tumor size, ground-glass opacities, maximum standardized uptake values, and molecular markers on preoperative biopsy were evaluated as preoperative markers. Comparisons between groups were conducted using standardized mean differences and random forest classification was used for prediction modeling. RESULTS: Of the 439 patients, 177 had at least 1 STAS-positive tumor, and 262 had no STAS-positive tumors. Overall, 179 STAS tumors and 293 non-STAS tumors were evaluated. Younger age (50 years or younger), solid tumor, size ≥2 cm, and maximum standardized uptake value ≥2.5 were independently predictive of STAS with prediction probabilities of 50%, 40%, 38%, and 40%, respectively. STAS tumors were more likely to harbor KRAS mutations and be PD-L1 negative. CONCLUSIONS: Young age (50 years or younger), larger (≥2 cm) solid tumors, high maximum standardized uptake values, and presence of KRAS mutation, are risk factors for STAS and can be considered for lobectomy. Smoking status and gender are still controversial risk factors for STAS.

Are Canadian general surgery residents ready for the 80-hour work week? A nationwide survey.

BACKGROUND: The purpose of this study was to describe Canadian general surgery residents' perceptions regarding potential implementation of work-hour restrictions. METHODS: An ethics review board-approved, Web-based survey was submitted to all Canadian general surgery residency programs between April and July 2009. Questions evaluated the perceived effects of an 80-hour work week on length of training, operative exposure, learning and lifestyle. We used the Fisher exact test to compare senior and junior residents' responses. RESULTS: Of 360 residents, 158 responded (70 seniors and 88 juniors). Among them, 79% reported working 75-100 hours per week. About 74% of seniors believed that limiting their work hours would decrease their operative exposure; 43% of juniors agreed (p < 0.001). Both seniors and juniors thought limiting their work hours would improve their lifestyle (86% v. 96%, p = 0.12). Overall, 60% of residents did not believe limiting work hours would extend the length of their training. Regarding 24-hour call, 60% of juniors thought it was hazardous to their health; 30% of seniors agreed (p = 0.001). Both senior and junior residents thought abolishing 24-hour call would decrease their operative exposure (84% v. 70%, p = 0.21). Overall, 31% of residents supported abolishing 24-hour call. About 47% of residents (41% seniors, 51%juniors, p = 0.26) agreed with the adoption of the 80-hour work week. CONCLUSION: There is a training-level based dichotomy of opinion among general surgery residents in Canada regarding the perceived effects of work hour restrictions. Both groups have voted against abolishing 24-hour call, and neither group strongly supports the implementation of the 80-hour work week.