February 2022

This prospective, randomized, multicenter non-inferiority trial (FAME 3) found that for patients with three-vessel coronary artery disease, percutaneous coronary intervention (PCI) guided by fractional flow reserve (FFR) measurement failed non-inferiority when compared to coronary artery bypass grafting (CABG) in a one-year composite outcome of death from any cause, myocardial infarction, stroke, or repeat revascularization, offering strong evidence that surgical intervention for coronary disease still remains the preferred, gold standard of care in select patients.

Summary:
The superiority of percutaneous coronary intervention (PCI) versus coronary artery bypass grafting (CABG) for coronary artery disease (CAD) has long been a hotly debated topic, particularly for patients with complex, multivessel disease. While studies in the past have shown improved outcomes in patients who underwent CABG, these older studies have rarely included second-generation drug-eluting stents in the PCI group, nor have they routinely measured fractional flow reserve (FFR) to guide PCI. FFR is an index of stenosis severity, and provides a more accurate assessment of the hemodynamic significance of a coronary stenosis than an angiogram alone. These considerations are important given that newer stents have improved outcomes including lower rates of in-stent thrombosis, restenosis, and myocardial infarction; furthermore, FFR encourages more judicious stenting, specifically the avoidance of stenting non-flow limiting lesions that respond well to medical therapy alone. This study sought to assess whether outcomes for patients with three-vessel CAD who underwent PCI were non-inferior to those who underwent CABG.

1500 patients were enrolled from 48 international sites and were randomly assigned 1:1 to either PCI or CABG. Patients included had angiographically-identified 3 vessel coronary artery disease not including the left main coronary artery, as defined by at least a 50% stenosis by visual estimation. The stenosis needed to be determined to be amenable to either PCI or CABG as determined by a heart team at the trial site. Exclusion criteria included recent STEMI, cardiogenic shock, or LVEF < 30%. The study was designed as an intention-to-treat, with the non-inferiority margin set to an upper boundary of less than 1.65 for the 95% confidence interval of the hazard ratio. The primary endpoint as a composite of 1-yea major adverse cardiac or cerebrovascular events as defined by death from any cause, MI, stroke, or repeat revascularization.

For the PCI group, the mean number of lesions was 4.3 with a mean number of stents of 3.7; FFR was measured in 82% of patients. For the CABG group, the mean number of lesions was 4.2 with a mean of 3.4 distal anastomoses; 97% received a left internal mammary artery (LIMA) gaft, and 25% received multiple arterial grafts. FFR-guided PCI did not meet non-inferiority in the primary end point, with 10.6% meeting the primary endpoint in the PCI group compared to 6.9% in the CABG group, yielding a hazard ratio of 1.5 (95% CI 1.1-2.2). However, CABG patients had longer hospital stays, episodes of major bleeding, arrhythmias, rates of AKI, and rehospitalizations at 30 days.

There are 3 obvious limitations to this study. The first is the short follow-up time of 1 year; prior trials have shown a greater diverging benefit of CABG over PCI in the longer term, particularly with respect to MI and repeat revascularization, which may not be captured here. Secondarily, the “heart team” determines which patients to include with regards to which lesions are amenable to both PCI and CABG, and that may vary greatly between centers. Finally, only 25% of CABG patients had multiple arterial grafts used, even though certain trials have demonstrated the benefit of multiple arterial grafts, such as radial grafts, over venous grafts.

As more and more traditionally operative procedures are moving toward minimally invasive or percutaneous techniques, it is crucial that we as surgeons carefully examine these alternative options and question whether the outcomes are truly better for our patients. While many patients may believe that minimally invasive approaches sound appealing, it is our job to keep abreast of the current literature that allows us to fully inform our patients and assist them in making the decision that will provide them the greatest long-term benefit; this study shows that CABG remains superior as the approach to three-vessel coronary artery disease.

Resident autonomy in routine cases has decreased by two-thirds over the past 15 years. There was no increase in patient morbidity or mortality when residents performed cases independently, and operative time actually decreased when the attending was not scrubbed. These commonly cited rationales for limiting resident autonomy are not borne out in the data, and efforts to increase resident operative autonomy (and therefore readiness for independent practice) are needed.

Summary:
Resident operative autonomy has been steadily declining, in part due to concerns over patient safety and OR efficiency. At the same time, faculty have expressed concerns that graduates are less prepared for independent practice. This study investigated the relationship between resident autonomy, patient outcomes, and operative duration.

This retrospective study utilized the VA Surgical Quality Improvement Program (VASQIP) database to look at 698,391 general/vascular surgery cases from 2004 to 2019. “Core cases” were identified using CPT code and sorted into 3 categories: AP - attending primary surgeon, AR - attending and resident, or RP - resident primary with attending supervising but not scrubbed. Of the 698,391 total cases, 392,284 “core cases” were selected, of which 38,483 (6%) were RP cases. Most of these were hernia repair (55%), cholecystectomy (18%), amputation (17%), appendectomy (7%), or open colectomy (3%). The number of RP cases significantly decreased from 15% in 2004 to 5% in 2019 (p<0.001).

RP cases were generally sicker (higher ASA class) and more likely to be emergent cases. Operative times were also increased with resident involvement, but RP cases were faster than AR cases on average. After adjusting for baseline demographics, case type, and year of procedure, mortality was no different between groups. Complications were higher in the AR group but not in the RP group.

This Phase 3 Clinical Trial in in patients with advanced, unresectable hepatocellular carcinoma found that atezolizumab+bevacizumab improved overall survival, progression free survival and quality of life in previously untreated patients with advanced HCC as compared to sorafenib. Relevant to surgeons, combination therapy increased tumor response rates, highlighting a potential role as a neoadjuvant approach to convert unresectable tumors to resectable.

Summary:
Hepatocellular carcinoma (HCC) is an aggressive tumor often diagnosed advanced in its course with 5-year survival at 18%. Curative therapy is limited to surgical resection or transplant, though most patients are ineligible. A variety of other treatment modalities exist, including liver directed (ablation, chemo/radioembolization) and medical therapies. Options often depend on extent of disease (notably the presence of major vascular invasion) and the degree of liver dysfunction. Medical therapeutic options in HCC have been lacking. In 2008 the SHARP trial reported a modest survival benefit to sorafenib, a multi-kinase inhibitor. Sorafenib has been the standard systemic treatment for years, and multiple groups have compared its efficacy with liver directed therapies. Recently other directed therapies have been explored, including immune-checkpoint blockade.

This phase 3 trial, published in 2020, compared atezolizumab (anti-PD-L1) plus bevacizumab (anti-VEGF) with sorafenib in patients with advanced, unresectable HCC. The concept behind atezolizumab+bevacizumab was that VEGF signaling mediates immunosuppression in the local tumor environment. They enrolled 501 patients (336 atezo/bev) with advanced HCC with a median follow up of 8.6 months. Interestingly, this trial included patients with tumors that were more extensive than other phase 3 trials, including those with significant macrovascular invasion or >50% liver involvement. The combination therapy of atezolizumab+bevacizumab resulted in increased overall survival, progression-free survival and objective response rates compared to sorafenib (67% vs 55% at 12 months, 6.8 vs 4.3 months, and 27.3% vs 11.9% respectively). They additionally found significantly prolonged time to deterioration of patient reported quality of life with atezolizumab/bevacizumab. In terms of adverse events, approximately 15% in the atezolizumab/bevacizumab group discontinued therapy early as opposed to 10% in the sorafenib group. The limitations of this study are that patients and providers were not blinded to the treatments, and the trial did not include anyone with Child-Pugh B or C cirrhosis. They used independent and blinded reviewers to assess response rates.

The authors demonstrated that atezolizumab+bevacizumab improves overall survival, progression free survival and quality of life in previously untreated patients with advanced HCC as compared to sorafenib. Though this is a study in advanced, non-surgical patients, it has ramifications for surgeons. For example, the combination therapy demonstrated 5.5% complete response and 21.8% partial response, as opposed to 0% and 12% respectively with sorafenib. Further studies are warranted to establish if the combination of atezolizumab and bevacizumab can be used in selected patients as a neoadjuvant approach to convert unresectable tumors to resectable. Additional research will also be needed to optimize how systemic therapies can integrate with liver-directed interventional approaches. 

Challenges to recovery and quality of life after traumatic injury extend far beyond discharge from the index hospital admission. This work sought to determine if these long-term outcomes can be effectively quantified and monitored via self-administration of a validated survey when included as part of routine trauma follow up.

Summary:
As the number of patients who survive traumatic injury continues to increase, so too does the need to develop ways to better support recovery outside the hospital. Namely, trauma patients face significant physical and mental challenges in the weeks to months post discharge that are difficult to quantify, much less adequately address. The trauma group at Penn has been attempting to better understand long term outcomes after traumatic injury by evaluating the functional, psychological, emotional, and social impact of injury among survivors over time. Such detriments in health-related quality of life can be captured through tools that assess outcomes from the patient perspective, such as the Patient-Reported Outcomes Measurement Information System 29 (PROMIS-29) instrument. This NIH validated survey focuses on 7 domains including physical function, anxiety, depression, fatigue, sleep disturbance, pain interference, and ability to participate in social activities and translates the findings to t-scores that can be compared to a general reference population or across groups. The Penn group previously used PROMIS instruments to find that patients who were admitted with a firearm injury experienced detriments in patient reported outcomes for years after injury, highlighting that this tool can be used to identify areas for intervention and longitudinal care in trauma.

Like many other medical fields, much of the work in trauma focused on administering the PROMIS instrument over the phone, but in this work from Hatchimonji et al, the authors sought to determine if this tool could be self-administered in clinic as part of the routine follow up after traumatic injury. To achieve this, the PROMIS-29 survey was administered in the waiting room via tablet after instruction from a trained medical assistant. Of 267 patients, 103 patients completed the survey at least one time, with another 10 patients completing the survey a second time at their follow up visit approximately 2 weeks later. Scores for these patients were worse than the control reference population in all healthcare related quality of life domains assessed by the instrument, in particular pain interference and physical function.

This work not only demonstrates the burden of diminished quality of life after trauma, but that self-administered surveys are a practical and effective method to monitor long-term outcomes. Future work will identify ways to improve survey completion rate, trial applicability across institutions, and translate the findings to target effective interventions to improve quality of life.