Adjuvant Therapy After Neoadjuvant Therapy for Esophageal Cancer: Who Needs It?

OBJECTIVE: We hypothesized that, on average, patients do not benefit from additional adjuvant therapy after neoadjuvant therapy for locally advanced esophageal cancer, although subsets of patients might. Therefore, we sought to identify profiles of patients predicted to receive the most survival benefit or greatest detriment from adding adjuvant therapy. BACKGROUND: Although neoadjuvant therapy has become the treatment of choice for locally advanced esophageal cancer, the value of adding adjuvant therapy is unknown. METHODS: From 1970 to 2014, 22,123 patients were treated for esophageal cancer at 33 centers on 6 continents (Worldwide Esophageal Cancer Collaboration), of whom 7731 with adenocarcinoma or squamous cell carcinoma received neoadjuvant therapy; 1348 received additional adjuvant therapy. Random forests for survival and virtual-twin analyses were performed for all-cause mortality. RESULTS: Patients received a small survival benefit from adjuvant therapy (3.2±10 months over the subsequent 10 years for adenocarcinoma, 1.8±11 for squamous cell carcinoma). Consistent benefit occurred in ypT3-4 patients without nodal involvement and those with ypN2-3 disease. The small subset of patients receiving most benefit had high nodal burden, ypT4, and positive margins. Patients with ypT1-2N0 cancers had either no benefit or a detriment in survival. CONCLUSIONS: Adjuvant therapy after neoadjuvant therapy has value primarily for patients with more advanced esophageal cancer. Because the benefit is often small, patients considering adjuvant therapy should be counseled on benefits versus morbidity. In addition, given that the overall benefit was meaningful in a small number of patients, emerging modalities such as immunotherapy may hold more promise in the adjuvant setting.

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.

Exploring ventricular dysfunction and poor venous drainage during robotic mitral valve surgery.

BACKGROUND: del Nido (DN) cardioplegia is commonly used during robotic mitral valve surgery. Poor venous drainage during surgery may result in venous backpressure and washout of this one-shot cardioplegia, limiting its cardioprotective effects. METHODS: One hundred eighty-seven patients undergoing isolated robotic mitral valve surgery, from January 2015 to July 2017, were retrospectively reviewed. Intraoperative central venous pressure (CVP) tracings were reviewed and venous drainage was categorized as good or poor and the relationship of the quality of venous drainage to postoperative ventricular dysfunction (operationalized as the need for inotropic support during and after weaning from cardiopulmonary bypass [CPB]) was assessed. RESULTS: Drainage was judged to be good in 107 patients and poor in 79 patients. On univariate analysis, 23 patients (41%) with good drainage required inotropic support whereas 33 patients (59%) with poor drainage required inotropic support (P = .0025). On multivariable analysis, poor venous drainage remained significantly associated with inotropic use even after adjusting for cross-clamp and CPB time. Inotrope use was associated with significantly longer intensive care unit length of stay (P = .027). CONCLUSION: Maintenance of excellent venous drainage, as assessed by CVP monitoring, should be a high priority in isolated robotic mitral valve surgery undertaken with DN cardioplegia.

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.

Thoracoabdominal Esophagectomy: Then and Now.

BACKGROUND: Open approaches for esophagectomy are often still useful; of these, left thoracoabdominal esophagectomy (TAE) is poorly understood and often criticized. Hence, we examined TAE's worldwide utilization, survival, and present-day use and outcomes at our institution compared with contemporary national averages. METHODS: The Worldwide Esophageal Cancer Collaboration database includes 8854 patients who underwent esophagectomy for cancer between 2005 and 2014, a period when TAE was our center's most common approach. Two propensity score-matched models were constructed: worldwide TAE vs worldwide non-TAE (751 matched pairs); and our high-volume center TAE vs worldwide non-TAE (273 matched pairs). All-cause mortality was compared between matched groups. Institutional TAE data from 2017 to 2021 were assessed for present-day use and outcomes. RESULTS: Worldwide, propensity score-matched patients undergoing TAE had a median of 20 lymph nodes resected vs 17 after non-TAE (P < .0001). Five-year survival was 34% for worldwide TAE vs 42% for worldwide non-TAE groups (P = .04). Three-year matched survival was 52% for high-volume TAE compared with 54% for worldwide non-TAE groups (P = .1). From 2017 to 2021 at our institution, 90 (26%) of 346 esophagectomies were performed by TAE. Pneumonia developed in 5 patients (5.6%), with 88 patients (98%) alive at 30 days, comparable to contemporary averages of The Society of Thoracic Surgeons. CONCLUSIONS: When it is performed as the primary approach in high volumes, TAE can have comparable outcomes to non-TAE with low morbidity. At present, we find that TAE is most useful in patients with truncal obesity, prior abdominal operations, and locally advanced cardia tumors with potential for variable extent of resection.

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.

The modified frozen elephant trunk may outperform limited and extended-classic repair in acute type I dissection.

OBJECTIVES: A better surgical approach for acute DeBakey type I dissection has been sought for decades. We compare operative trends, complications, reinterventions and survival after limited versus extended-classic versus modified frozen elephant trunk (mFET) repair for this condition. METHODS: From 1 January 1978 to 1 January 2018, 879 patients underwent surgery for acute DeBakey type I dissection at Cleveland Clinic. Repairs were limited to the ascending aorta/hemiarch (701.79%) or extended through the arch [extended classic (88.10%) or mFET (90.10%)]. Weighted propensity score matched established comparable groups. RESULTS: Among weighted propensity-matched patients, mFET repair had similar circulatory arrest times and postoperative complications to limited repair, except for postoperative renal failure, which was twice as high in the limited group [25% (n = 19) vs 12% (n = 9), P = 0.006]. Lower in-hospital mortality was observed following limited compared to extended-classic repair [9.1% (n = 7) vs 19% (n = 16), P = 0.03], but not after mFET repair [12% (n = 9) vs 9.5% (n = 8), P = 0.6]. Extended-classic repair had higher risk of early death than limited repair (P = 0.0005) with no difference between limited and mFET repair groups (P = 0.9); 7-year survival following mFET repair was 89% compared to 65% after limited repair. Most reinterventions following limited or extended-classic repair underwent open reintervention. All reinterventions following mFET repair were completed endovascularly. CONCLUSIONS: Without increasing in-hospital mortality or complications, less renal failure and a trend towards improved intermediate survival, mFET may be superior to limited or extended-classic repair for acute DeBakey type I dissections. mFET repair facilitates endovascular reintervention, potentially reducing future invasive reoperations and warranting continued study.

Comparison of Outcomes and Discharge Location After Transcatheter vs. Surgical Aortic Valve Replacement With Prior Coronary Artery Bypass Grafting.

Background: Published trials have shown that transcatheter aortic valve replacement (TAVR) is a safe alternative to surgical aortic valve replacement (SAVR) after prior coronary artery bypass grafting (CABG). However, differences in morbidity and discharge location between the 2 procedures are less thoroughly characterized. Methods: From January 1, 2006 to January 7, 2020, 1059 patients with severe aortic stenosis after CABG underwent either SAVR (n = 315/30%), transfemoral TAVR (TF-TAVR) (n = 575/54%), or alternative access TAVR (n = 169/16%) at a single, tertiary care, academic institution. Propensity-weighted matching was used to compare morbidity, mortality, length of postprocedure stay, and nonhome discharge between TF-TAVR (effective n = 163) and SAVR (effective n = 163) groups. Results: Among propensity-weighted groups, the TF-TAVR group experienced fewer transfusions than the SAVR group (effective n = 16 [9.5%] vs. 132 [81%]; p < 0 .0001), less new-onset atrial fibrillation (effective n = 5.1 [3.1%] vs. 43 [27%]; p = 0.009), and less prolonged mechanical ventilation >24 â€‹hours (effective n = 0.41 [0.25%] vs. 30 [18%]; p <0.0001). Permanent pacemaker implant was 9.3% (effective n = 13) after TF-TAVR vs. 5.5% (effective n = 7.9; p = 0.2) after SAVR, stroke 0.41% (effective n = 0.67) vs. 2.1% (effective n = 3.5; p = 0.2), and operative mortality 0.5% (effective n = 0.8) vs. 1.7% (effective n = 2.8; p = 0.8). The TF-TAVR group had shorter postprocedure lengths of stay (2.0 vs. 7.6 days; p < 0.0001). Discharge home was more common after TF-TAVR than SAVR (effective n = 156 [95%] vs. 118 [73%]; p = 0.01). Conclusions: For patients developing severe aortic stenosis after CABG, TF-TAVR rather than SAVR should be strongly considered because of lower morbidity, shorter length of stay, and greater likelihood of home discharge.

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.

Similar long-term survival after isolated bioprosthetic versus mechanical aortic valve replacement: A propensity-matched analysis.

OBJECTIVES: Improved durability and preference to avoid anticoagulation have led to increasing use of bioprostheses in younger patients despite the need for eventual reoperation. Therefore, we compared in-hospital complications, reoperation, and survival after bioprosthetic and mechanical aortic valve replacement. METHODS: From January 1990 to January 2020, 6143 patients underwent isolated aortic valve replacement at Cleveland Clinic; 637 patients received a mechanical prosthesis and 5506 a bioprosthesis. Propensity matching identified 527 well-matched pairs (83% of possible matches) for comparison of perioperative outcomes. The average age of patients was 54 years in the bioprosthesis group and 55 years in the mechanical prosthesis group. Random Forest machine-learning analysis was performed to compare survival using the entire cohort of 6143 patients. RESULTS: Among matched patients, major in-hospital complications, including stroke, deep sternal wound infection, and reoperation for bleeding, were similar, as was in-hospital mortality (2 in the bioprosthesis group [0.38%] vs 3 in the mechanical prosthesis group [0.57%]; P > .9). Patients receiving a bioprosthesis had shorter hospital stays (median 6 vs 7 days, P < .0001). Fifty-one patients (32% at 14 years) in the bioprosthesis group and 17 patients in the mechanical prosthesis group (8% at 14 years) underwent reoperation (P [log-rank] < .0001); 5-year survival after reoperation was 85% versus 82% (P = .6). Risk-adjusted Random Forest prediction of 18-year survival was 60% in the bioprosthetic group and 58% in the mechanical prosthesis group. CONCLUSIONS: Aortic valve bioprostheses are associated with excellent short-term outcomes and 18-year survival similar to that of patients receiving mechanical valves. Reoperation does not adversely affect survival. These results suggest that risk for reoperation alone should not deter the use of bioprostheses in younger patients.

A comparative study of robotic and laparoscopic approaches to Heller myotomy.

OBJECTIVE: Minimally invasive Heller myotomy for achalasia is commonly performed laparoscopically, but recently done with robotic assistance. We compare outcomes of the 2 approaches. METHODS: From January 2010 to January 2020, 447 patients underwent Heller myotomy with anterior fundoplication (170 with robotic assistance and 277 laparoscopically). End points included short-term and longitudinal esophageal emptying according to timed barium esophagram, symptom relief according to Eckardt score, and time-related reintervention. Normal esophageal morphology, present in 328 patients, was defined as nonsigmoidal with width <5 cm. We performed a propensity score--matched analysis to evaluate outcomes among robotic and laparoscopic groups. RESULTS: Timed barium esophagrams showed complete emptying at 5 minutes in 58% (77/132) of the robotic group and 48% (115/241) of the laparoscopic group in the short term (within 6 months of surgery). In the propensity-matched patients with normal esophageal morphology, the robotic group had a higher longitudinal prevalence of complete emptying of barium at 5 minutes (54% vs 34% at 4 years; P = .05), better intermediate-term Eckardt scores (1.7% vs 10% > 3 at 4 years; P = .0008), and actuarially fewer reinterventions (1.2% vs 11% at 3 years; P = .04). CONCLUSIONS: Both robotically assisted and laparoscopic Heller myotomy had excellent outcomes in patients treated for achalasia. In a matched subgroup of patients with normal esophageal morphology within this heterogeneous disease, the robotic approach might be associated with greater esophageal emptying, palliation of symptoms, and freedom from reintervention in the intermediate term. Long-term analysis would be important to determine if this trend persists.

Outcomes of Open Versus Endovascular Repair of Descending Thoracic and Thoracoabdominal Aortic Aneurysms.

BACKGROUND: Open repair is the standard of care for patients with descending thoracic and thoracoabdominal aortic aneurysms. Although effective, surgery carries a high risk of morbidity and mortality. Endovascular stent grafts were introduced to treat these aneurysms in patients considered too high risk for open repair. Early results are promising, but later results are incompletely known. Therefore, we sought to compare short- and intermediate-term outcomes of open vs endovascular repair for these aneurysms. METHODS: From 2000 to 2010, 1053 patients underwent open (n = 457) or endovascular (n = 596) repair of descending thoracic and thoracoabdominal aortic aneurysms at Cleveland Clinic. To balance patient characteristics between these groups, propensity score matching was performed, yielding 278 well-matched pairs (61% of possible pairs). End points included short- and long-term outcomes. RESULTS: In matched patients, compared with endovascular stenting, open repair achieved similar in-hospital death (n = 23 [8.3%] vs n = 21 [7.6%], P = .80) and occurrence of paralysis and stroke (n = 10 [3.6%] vs n = 6 [2.2%], P = .30), despite a longer postoperative stay (median 11 vs 6 days), more dialysis-dependent acute renal failure (n = 24 [8.6%] vs n = 9 [3.3%], P = .008), and prolonged ventilation (n = 106 [46%] vs n = 17 [6.3%], P < .0001). Open repair resulted in better 10-year survival than endovascular repair (52% vs 33%, P < .0001), and aortic reintervention was less frequent (4% vs 21%, P < .0001). Despite a decrease in the first postoperative year, average aneurysm size did not recover to normal range after endovascular stenting. CONCLUSIONS: Open repair of descending thoracic and thoracoabdominal aneurysms can achieve acceptable short-term outcomes with better intermediate-term outcomes than endovascular repair.

Non-small cell lung cancer in never- and ever-smokers: Is it the same disease?

OBJECTIVES: To investigate differences in presentation, pathology, and outcomes after resection of non-small cell lung cancer (NSCLC) in never-smokers versus ever-smokers. METHODS: From January 2006 to July 2016, 172 never-smokers and 1376 ever-smokers with NSCLC underwent pulmonary resection. The 2 cohorts were matched on patient characteristics, histopathological cancer cell type, and pathological stage group using a weighted balancing score, and overall survival and cancer recurrence were compared by pathological stage. Random forests for survival was used to identify granular cancer characteristics with different survival and cancer recurrence importance between groups. RESULTS: In never-smokers, the prevalence of NSCLC was more frequent in women than in men (63% [n = 109] vs 45% [n = 63]). Compared with ever-smokers, never-smokers had less upper-lobe disease (53% [n = 91] vs 62% [n = 855]) and more adenocarcinoma (88% [n = 151] vs 62% [n = 845]). Postoperative complications were similar. Never-smokers had a lower prevalence of non-lung cancer deaths than ever-smokers (13% vs 23% at 5 years; P = .006). Among matched pairs, never-smokers had better overall survival at 5 years in pathological stage I (96% vs 78%), but worse survival in stage II (54% vs 78%). Tumor size, N category, and histopathological cell type were more important drivers of mortality and cancer recurrence in never-smokers than in ever-smokers. CONCLUSIONS: NSCLC in never-smokers affects women more than men and presents with different anatomic and histopathological distributions. Matched never-smokers have better or equivalent outcomes than ever-smokers in pathological stage I cancer, but are less likely to survive and to be cured of cancer as tumor burden increases. These findings suggest that there might be unique tumor or host behaviors differentially impacting survival of never- and ever-smoking patients with NSCLC.

Outcomes after resection of primary cardiac sarcoma.

Objective: To evaluate the outcomes of surgical resection of malignant primary cardiovascular tumors. Methods: From 1983 to 2018, 32 patients underwent surgical resection of malignant primary cardiovascular sarcoma at Cleveland Clinic. Mean age was 48 ± 15 years, and 19 (59%) were women. Outcomes are compared between those with complete resection and those without, and in relation to primary location. Results: The most common histologic subtypes were angiosarcoma (n = 8 [25%]) and high-grade undifferentiated sarcoma (n = 7 [22%]). Fourteen (44%) involved the left heart, 9 (28%) the right heart, 8 (25%) the pulmonary arteries, and 1 (3%) the aorta. There was clinical evidence of isolated extracardiac metastases in 8 (25%). Six (19%) patients were deemed unresectable at surgery, undergoing biopsy and palliative debulking followed by referral for definitive chemotherapy and/or radiation. The remaining 26 (81%) patients underwent 31 tumor resections with curative intent. Seven (22%) patients had previously undergone a resection or biopsy at another institution. There were 10 second-time resections, 2 third-time resections, 1 fourth-time resection, and no operative mortalities. Median survival was 3 years, with estimated survival at 6 months and 1, 5, and 10 years of 90%, 73%, 31%, and 17%, respectively. Of the 8 (25%) who were considered disease-free following surgery, 4 experienced recurrences during follow-up. Conclusions: Primary cardiac sarcoma continues to be a challenging disease with poor prognosis. Aggressive resection with curative intent, frequent surveillance for local and distant recurrence, and systemic and local multimodality treatment optimizes outcomes.

Effect of High-Density Lipoprotein Cholesterol Levels on Overall Survival and Major Adverse Cardiovascular and Cerebrovascular Events.

Several studies designed to augment high density lipoprotein (HDL) levels have so far been unsuccessful in reducing rates of major adverse cardiovascular and cerebrovascular events (MACCE). In this study, we report the effect of HDL-C levels on overall survival outcomes and rates of MACCE following percutaneous coronary intervention (PCI). We reviewed patients who underwent PCI at the Cleveland Clinic from 2005 to 2017 and followed them through the end of 2018. Restricted cubic splines incorporated into Cox proportional hazard regression models were used to assess the outcomes. The HDL-C level associated with the lowest mortality was used as a reference value.15,633 patients underwent PCI during the study period, of which 70% were male, 81% were white, and 73% were on statins. The mean age at the time of procedure was 65.8 ± 11.8 years. After adjusting for demographics, co-morbidities, lipid profile, statin use, and date of procedure, our model demonstrated a U-shaped association between HDL-C and overall mortality, with HDL-C levels of 30-50 mg/dl associated with the most favorable outcomes, and HDL-C levels < 30 mg/dl or > 50 mg/dl associated with worse outcomes. A sensitivity analysis in men yielded a similar U-shaped association. In conclusion, our study shows that both low and high levels of HDL-C are associated with worse overall survival, with no effect on rates of MACCE in PCI patients. Further studies are required to understand the mechanism of this association between elevated HDL-C levels with increased overall mortality in patients with atherosclerotic cardiovascular disease (ASCVD).

Temporal trend and associated risk factors for new-onset atrial fibrillation following cardiac valve surgery.

AIMS: Post cardiac surgery atrial fibrillation (POAF) is common, with adverse implications. However, relatively little is known regarding the time varying nature of risk factors associated with POAF. We describe variation in POAF along with its associated risk factors. METHODS: Medical records of adult patients undergoing cardiac valve surgery from 2003-13, without a history of pre-operative AF were analyzed retrospectively. POAF was adjudicated using inpatient and outpatient electrocardiograms (EKG). Risk of AF over time along with time-varying risk factors were estimated using multiphase non-linear logistic mixed effects model. RESULTS: 10,461 patients with 100,149 EKGs were analyzed [median follow-up 4 months (IQR 48 hours-2 years)]. AF prevalence changed with time since surgery and two distinct phases were identified. Prevalence peaked to 13% at 2 weeks (early phase) and 9% near 7 years post-operatively (late phase). Older age, greater severity of preoperative tricuspid valve (TV) regurgitation, mitral valve replacement and prior cardiac surgery were time-independent risk factors for POAF. TV repair was associated with a decreased risk of early phase POAF. Pre-operative blood urea nitrogen, peripheral vascular disease and hypertension were associated with a higher risk of late phase POAF. CONCLUSIONS: POAF risk shows two distinct phases with an early peak and a late gradual rise, each associated with a different set of risk factors.

Microplegia vs 4:1 Blood Cardioplegia: Effectiveness and Cost Savings in Complex Cardiac Operations.

BACKGROUND: Microplegia has been studied during isolated coronary artery bypass grafting and valve surgery but not in more complex operations. Objectives of this study were to demonstrate safety and effectiveness of microplegia relative to Buckberg cardioplegia during these operations. METHODS: From January 2012 to January 2017, 242 patients underwent multicomponent operations with simplified microplegia delivered via syringe pump and 10,512 with modified Buckberg cardioplegia. Operations included aortic root, arch, or ascending aorta replacement in 424 (94%) patients, aortic valve surgery in 324 (72%) patients, and concomitant coronary artery bypass grafting in 47 (10%) patients. Outcomes were compared in 226 propensity-matched pairs. RESULTS: There was no difference in median postoperative troponin T between groups after adjusting for aortic clamp time. Microplegia patients received significantly less crystalloid with their cardioplegia (mean 27 ± 8.0 mL/operation vs 735 ± 357 mL/operation; P < .001) and had lower peak intraoperative glucose (196 ± 40 mg/dL vs 248 ± 69 mg/dL; P < .001). Microplegia and Buckberg groups had similar in-hospital mortality (2.7% [n = 6] vs 2.2% [n = 5]; P = .8), stroke (2.2% [n = 5] vs 3.6% [n = 8]; P = .4), renal failure (8% [n = 18] vs 5.8% [n = 13]; P = .4), prolonged ventilation (23% [n = 51] vs 24% [n = 54]; P = .7), median postoperative length of stay (both 8.1 days; P > .9), and median red cell units administered to patients requiring transfusion (4 units vs 3 units; P = .14). The mean cost of cardioplegia per case with microplegia was 1/26th that of Buckberg cardioplegia. CONCLUSIONS: Our simplified microplegia technique offers several advantages over Buckberg cardioplegia without compromising myocardial protection or safety in complex, multicomponent operations with extended aortic clamp times.

Consequences of Delayed Chest Closure During Lung Transplantation.

BACKGROUND: Delayed chest closure is commonly used for cardiac surgery. However, insufficient data exist to guide its management in immunosuppressed lung transplantation patients, with unclear long-term consequences. METHODS: We performed 769 lung transplantations between January 2009 and January 2016. Of these, 47 (6%) required delayed chest closure because of coagulopathy, respiratory intolerance, and hemodynamic instability. On multivariable analysis, risk factors for delayed chest closure included double-lung transplantation and longer ischemic times. To account for differences between the 2 groups, we performed propensity matching, generating 46 well-matched pairs. RESULTS: Among matched patients with appropriate antimicrobial prophylaxis, we found no difference in 30-day prevalence of pneumonia, empyema, Clostridium difficile, bloodstream, and deep wound infections. There was also no difference in 6-month composite infections. However, delayed chest closure patients received more transfusions within 5 days of transplantation (median, 7 vs 3 units; P < .001), had more intubations > 5 days (80% vs 41%, P < .001), had more severe primary graft dysfunction (39% vs 17%, P = .044), had a longer hospital stay (median, 61 vs 25 days; P < .001), and had worse pulmonary function tests 6 years after transplant (P = .019). Fortunately, estimated survival at 6 months, 1 year, and 5 years between delayed and primary chest closure groups was similar (82%, 76%, and 39% vs 84%, 75%, and 50%, respectively; P = .23). CONCLUSIONS: Use of delayed chest closure does not yield more infections or worse long-term survival. However it may be associated with increased in-hospital morbidities and worse long-term pulmonary function.

Impact of timing of atrial fibrillation, CHA2DS2-VASc score and cancer therapeutics on mortality in oncology patients.

OBJECTIVES: To investigate timing and age distribution of atrial fibrillation (AF) in selected oncology patients, and the impact of AF timing, CHA2DS2-VASc score and cancer therapeutics on mortality. METHODS: This is a retrospective cohort study of oncology patients referred to the cardio-oncology service from 2011 to 2018 for echocardiographic cardiosurveillance and/or pre-existing cardiovascular risk factor/disease management. Rates of first AF diagnosis was assessed using a parametric multiphase hazard model (predictive modelling) and non-parametrically by Kaplan-Meier with transformations tested using a bootstrap methodology. RESULTS: Among 6754 patients identified, 174 patients had their first AF diagnosis before cancer while 609 patients had their first diagnosis of AF after cancer. Most first AF diagnosis occurred at/early after cancer diagnosis. Increasing AF prevalence at time of cancer diagnosis was seen across older age groups ranges. Diagnosis of cancer at an older age and exposure to cardiotoxic treatment (anthracyclines, HER2-neu inhibitors, tyrosine kinase inhibitors including ibrutinib and radiation) were associated with an increased risk of AF.Modelling of the hazard function of AF identified a high left-skewed peak within 3 years after cancer diagnosis ('early phase'), followed by a gradual late slight rise 3 years after cancer diagnosis ('late phase'). AF diagnosis was only associated with death in the early phase (p<0.001), while CHA2DS2-VASc score was only associated with death in the late phase (p<0.001). CONCLUSIONS: This study reports a nuanced/complex relationship between AF and cancer. First diagnosis of AF in patients with cancer was more common at/early after cancer diagnosis, especially in older patients and those exposed to cardiotoxic treatment. Pre-existing AF or a diagnosis of AF within 3 years after cancer diagnosis carried a negative prognosis. CHA2DS2-VASc score did not relate to mortality in those that developed AF within 3 years of cancer diagnosis.