Short- and long-term outcomes of thoracoscopic esophagectomy in the prone position for esophageal squamous cell carcinoma in patients with obstructive ventilatory disorder: a propensity score-matched study.

BACKGROUND: Many patients with esophageal squamous cell carcinoma (ESCC) have obstructive ventilatory disorder (OVD), which is considered a risk factor for postoperative pneumonia. It has been reported that thoracoscopic esophagectomy in the prone position (TEP) is less invasive and is associated with fewer postoperative respiratory complications compared with open esophagectomy. This matched-cohort study aimed to elucidate the safety and oncologic outcomes of ESCC patients with OVD who undergo TEP. METHODS: In this matched-cohort study, 237 patients with ESCC who underwent TEP between 2010 and 2018 were divided into two groups based on forced expiratory volume in 1 s/forced vital capacity. Postoperative complications (Clavien-Dindo classification grade II or higher), overall survival (OS), and disease-free survival (DFS) were compared between the two groups. RESULTS: Based on their propensity scores, 75 patients with normal respiratory function (NRF) and 75 with OVD were selected. The rates of postoperative pneumonia were not significantly different between the two groups (NRF group vs OVD group: 18.7% vs 18.7%; P = 1.000). The rates of recurrent laryngeal nerve palsy and anastomotic leakage were also not significantly different (NRF group vs OVD group: 12.0% vs 18.7%, P = 0.365; 18.7% vs 18.7%, P = 1.000). The 5-year OS and DFS rates in the NRF vs OVD groups were 66.2% vs 54.9% and 63.5% vs 52.9%, respectively, with no significant differences (P = 0.421, 0.197). CONCLUSIONS: TEP can be safely performed on ESCC patients with OVD and can result in an oncological efficiency equal to that of the NRF group.

Comparison of Long Term Outcomes After Endovascular Treatment Versus Bypass Surgery in Chronic Limb Threatening Ischaemia Patients with Long Femoropopliteal Lesions.

OBJECTIVE: There are currently two treatments available for patients with chronic limb threatening ischaemia (CLTI): open surgical bypass (OSB) and percutaneous transluminal angioplasty with/without stenting (PTA/S). The aim of this study was to compare short and long term outcomes between PTA/S and OSB in CLTI patients with long (GLASS grade III and IV) femoropopliteal disease. METHODS: This was a two centre retrospective study including all consecutive patients with CLTI undergoing first time lower extremity intervention at two distinct vascular surgical centres. Between 1 January 2012 and 1 January 2018, 1 545 CLTI consecutive limbs were treated for femoropopliteal GLASS grade III and IV lesions at two vascular surgical centres. Using covariables from baseline and angiographic characteristics, a propensity score was calculated for each limb. Thus, comparable patient cohorts (235 in PTA/S and 235 in OSB group) were identified for further analysis. The primary outcomes were freedom from re-intervention in the treated extremity and major amputation. Secondary outcomes were all hospital complications among the two patient groups. RESULTS: Total overall complication rates were significantly higher in the OSB group (20.42% vs. 5.96%, p < .001), especially wound infection/seroma rate that required prolonged hospitalisation and further treatment (7.65% vs. 0%, p < .001). After the median follow up of 61 months, re-intervention rates were significantly higher in the PTA/S group (log rank test, 44.68% vs. 29.79%, p = .002), but there was no significant difference in terms of major amputation rates between the two group of patients (log rank test, PTA/S 27.23% vs. OSB 22.13%, p = .17). CONCLUSION: Bypass surgery seems to be superior to PTA/S for GLASS grade III and IV femoropopliteal lesions in patients with CLTI in terms of long term re-intervention rates, but with considerably higher rates of post-operative complications. A larger cohort of patients in currently ongoing randomised trials, as well as prospective cohort studies are necessary to confirm these findings.

Achalasia and obesity: patient outcomes and impressions following laparoscopic Heller myotomy and Dor fundoplication.

PURPOSE: The optimal management of achalasia in obese patients is unclear. For those who have undergone Heller myotomy and fundoplication, the long-term outcomes and their impressions following surgery are largely unknown. METHODS: A retrospective review of patients who underwent laparoscopic Heller myotomy and Dor fundoplication (LHMDF) for achalasia was performed. From this cohort, Class 2 and 3 obese (BMI > 35 kg/m2) patients were identified for short- and long-term outcome analysis. RESULTS: Between 2003 and 2015, 252 patients underwent LHMDF for achalasia, and 17 (7%) patients had BMI > 35 kg/m2. Pre-operative Eckardt scores varied from 2 to 9, and at short-term (2-4 week) follow-up, scores were 0 or 1. Ten (58%) patients had available long-term (2-144 months) follow-up data. Eckardt scores at this time ranged from 0 to 6. Symptom recurrence was worse for patients with BMI > 40 kg/m2 compared to patients with BMI < 40 kg/m2. BMI was largely unchanged at long-term follow-up regardless of pre-intervention BMI. Most patients were satisfied with surgery but would have considered a combined LHMDF and weight-loss procedure had it been offered. CONCLUSION: LHMDF for achalasia in obese patients is safe and effective in the short term. At long-term follow-up, many patients had symptom recurrence and experienced minimal weight loss. Discussing weight-loss surgery at the time LHMDF may be appropriate to ensure long-term achalasia symptom relief.

High preoperative modified frailty index has a negative impact on short- and long-term outcomes of octogenarians with gastric cancer after laparoscopic gastrectomy.

BACKGROUND: The proportion of elderly patients who undergo surgery has rapidly increased. However, clinical indicators that predict outcomes are limited. Frailty is thought to estimate physiological reserves, although its use has not been evaluated in laparoscopic surgical patients. This study aimed to evaluate the significance of preoperative modified frailty index (PMFI) in octogenarians undergoing a laparoscopic gastrectomy. METHODS: We reviewed prospectively collected data from 119 patients with gastric cancer (GC) aged 80 years or older who underwent a radical laparoscopic gastrectomy (RLG) between January 2007 and December 2012. Three baseline frailty traits were measured using routine preoperative laboratory data: albumin < 3.4 g/dL, haematocrit < 35%, and creatinine > 2 mg/dL. Patients were categorized by the number of positive traits as follows: low preoperative modified frailty index (LPMFI): 0-2 traits and high preoperative modified frailty index (HPMFI): 3 traits. We compared patient characteristics, operative outcomes, pathological results, morbidity, and survival. RESULTS: A total of 43 (36.1%) patients were considered HPMFI, and 76 (63.9%) patients were considered LPMFI. HPMFI was associated with an increased risk of postoperative complications (HPMFI group: odds ratio 2.506; 95% CI, 1.113-5.643, P = 0.027). With a median follow-up of 39.0 months, the 3-year overall survival (OS), recurrence-free survival (RFS), and cancer-specific survival (CSS) rates for the entire cohort were 47.9, 34.3, and 51.7%, respectively. Significant differences were observed in OS (HPMFI group, 37.2%; LPMFI group, 53.9%; P = 0.038) and RFS (HPMFI group, 23.3%; LPMFI group, 40.5%; P = 0.012) between the groups, but no difference was found for CSS (HPMFI group, 43.5%; LPMFI group, 56.4%; P = 0.078). CONCLUSIONS: HPMFI based on an easily calculable preoperative measure may be useful for predicting postoperative complications and have a negative impact on 3-year OS and RFS after an RLG in octogenarians. Therefore, HPMFI can serve as a low-cost, simple screen for high-risk individuals who might suffer more than expected during the postoperative period after an RLG.

Outcomes according to body mass index following laparoscopic surgery in patients with colorectal cancer.

PURPOSE: Body mass index (BMI) may not be appropriate for different populations. Therefore, the World Health Organization (WHO) suggested 25 kg/m2 as a measure of obesity for Asian populations. The purpose of this report was to compare the oncologic outcomes of laparoscopic colorectal resection with BMI classified from the WHO Asia-Pacific perspective. PATIENTS AND METHODS: All patients underwent laparoscopic colorectal resection from September 2006 to March 2015 at a tertiary referral hospital. A total of 2408 patients were included and classified into four groups: underweight (n = 112, BMI <18.5 kg/m2), normal (n = 886, 18.5-22.9 kg/m2), pre-obese (n = 655, 23-24.9 kg/m2) and obese (n = 755, >25 kg/m2). Perioperative parameters and oncologic outcomes were analysed amongst groups. RESULTS: Conversion rate was the highest in the underweight group (2.7%, P < 0.001), whereas the obese group had the fewest harvested lymph nodes (21.7, P < 0.001). Comparing oncologic outcomes except Stage IV, the underweight group was lowest for overall (P = 0.007) and cancer-specific survival (P = 0.002). The underweight group had the lowest proportion of national health insurance but the highest rate of medical care (P = 0.012). CONCLUSION: The obese group had the fewest harvested lymph nodes, whereas the underweight group had the highest estimated blood loss, conversion rate to open approaches and the poorest overall and cancer-specific survivals.

Long-Term Effects of Postoperative Atrial Fibrillation following Mitral Valve Surgery.

BACKGROUND: New-onset postoperative atrial fibrillation (PoAF) is one of the most frequent yet serious complications following cardiac surgery. Long-term consequences have not been thoroughly investigated, and studies have included different cardiac operations. The objectives were to report the incidence and short- and long-term outcomes in patients with PoAF after mitral valve surgery. METHODS: This is a retrospective cohort study of 1401 patients who underwent mitral valve surgery from 2009 to 2020. Patients were grouped according to the occurrence of PoAF (n = 236) and the nonoccurrence of PoAF (n = 1165). Long-term outcomes included mortality, heart failure rehospitalization, stroke, and mitral valve reinterventions. RESULTS: The overall incidence of PoAF was 16.8%. PoAF was associated with higher rates of operative mortality (8.9% vs. 3.3%, p < 0.001), stroke (6.9% vs. 1.5%, p < 0.001), and dialysis (13.6% vs. 3.5%, p < 0.001). ICU and hospital stays were significantly longer in patients with PoAF (p < 0.001 for both). PoAF was significantly associated with an increased risk of mortality [HR: 1.613 (95% CI: 1.048-2.483); p = 0.03], heart failure rehospitalization [HR: 2.156 (95% CI: 1.276-3.642); p = 0.004], and stroke [HR: 2.722 (95% CI: 1.321-5.607); p = 0.007]. However, PoAF was not associated with increased mitral valve reinterventions [HR: 0.938 (95% CI: 0.422-2.087); p = 0.875]. CONCLUSIONS: Atrial fibrillation after mitral valve surgery is a common complication, with an increased risk of operative mortality. PoAF was associated with lower long-term survival, increased heart failure rehospitalization, and stroke risk. Future studies are needed to evaluate strategies that can be implemented to improve the outcomes of these patients.

Clinical impact of perirenal thickness on short- and long-term outcomes of gastric cancer after curative surgery.

Background: A variety of factors for short- and long-term outcomes have been reported after radical resection for gastric cancer (GC). Obesity and emaciation had been reported to be a cause of poor short- and long-term outcomes with gastrointestinal cancer. However, the indicators are still controversial. The purpose of this study was to evaluate the relationship between perirenal thickness (PT) and short- and long-term outcomes after radical surgery for GC. Methods: We analyzed the data of 364 patients with GC who underwent radical surgery. We evaluated the distance from the anterior margin of the quadratus lumborum muscle to the dorsal margin of the left renal pole using computed tomography (CT) as an indicator of PT. The association between PT and clinicopathological factors and short- and long-term outcomes was evaluated. Results: The PT data were divided into low, normal, and high groups by gender using the tertile value. We found that the PT low group was 121 patients, normal group was 121 patients, and high group was 122 patients. Multivariate analyses showed that the high PT group was an independent risk factor for a short-outcome after curative surgery in GC patients (odds ratio 2.163; 95% confidence interval [CI] 1.156-4.046; P = .016). And the low PT group was an independent risk factor for overall survival (hazard ratio 2.488; 95% CI 1.400-4.421; P = .0019) and relapse-free survival (hazard ratio 2.342; 95% CI 1.349-4.064; P = .0025) after curative surgery in GC patients. Conclusion: Perirenal thickness is a simple and useful factor for predicting short- and long-term outcomes after radical surgery for GC.

Considerations for the Utility of Real-World Evidence Beyond Trial Data in Advanced NSCLC: The Case of Frontline Tyrosine Kinase Inhibitors.

Background: To extend the discussion on the use of real-world evidence (RWE) in conveying the clinical value of treatment beyond trial data, the primary objective of this study was to assess if efficacy gains in progression-free survival (PFS) observed in randomized controlled trials (RCT) correlate with efficacy gains in the real-world setting. For this, we assessed the treatment benefit of three tyrosine kinase inhibitors (TKIs) in aNSCLC. Methods: Using matched cohorts identified in the Flatiron Health database (2011-2020), we mimicked the following cohorts of TKI versus platinum-based chemotherapy (PBC) from the following trials: (1) erlotinib, EURTAC; (2) afatinib, LUX-Lung 3; and (3) crizotinib, PROFILE 1014. Time to treatment discontinuation (TTD) hazard ratio (HR) was used as a proxy for PFS HR, the primary endpoint in the selected RCTs. HRs were calculated via Cox proportional hazard models. Results: Overall, 1,118 patients were included across the three RWE cohorts. Frontline TKI regimens had statistically significantly better real-world TTD than their matched PBC comparator group (HR 0.37, 95% confidence interval [CI] 0.30-0.44 for erlotinib; HR 0.42, 95% CI 0.32-0.55 for afatinib; HR 0.37, 95% CI 0.26-0.53 for crizotinib). The benefit in real-world OS was not different between TKIs and PBC patients, attributed to a high proportion of switching to subsequent therapy. Study findings of relative treatment benefit (HR) for real-world TTD and OS were deemed similar to those for PFS and OS from the pivotal RCTs. Conclusion: The relative treatment effect, measured as real-world TTD HR over the long term, was similar to trial-based PFS HR, implying that the clinical benefit of aNSCLC treatments conveyed in trials translated into the clinical setting. This is important, given that OS data interpretation is limited, even with longer follow-up. Additionally, our RWE analysis endorses TTD as a relevant endpoint to measure clinical benefit.

Pneumonectomy in Stage IIIA-N2 NSCLC: Should It Be Considered After Neoadjuvant Chemotherapy?

BACKGROUND: Owing to the expected poor long-term outcomes and high postoperative morbidity and mortality, patients with stage IIIA-N2 tumors candidate to pneumonectomy (PN) are usually excluded from surgery. This study aims to analyze the outcome of patients who underwent PN to prove its safety and feasibility. PATIENTS AND METHODS: We retrospectively analyzed data from 233 patients who underwent PN for N2 non-small-cell lung cancer (NSCLC) between 1998 and 2015. Eighty-five patients were occult N2 disease (group 1), whereas 148 patients underwent induction therapy (IT) for stage IIIA-N2 (group 2). RESULTS: Overall morbidity, postoperative mortality, and 90-day mortality rates were 46.8%, 2.6%, and 8.6%, respectively. The 2 groups (group 1 vs. 2) had similar postoperative and 90-day mortality rates: 2.4% versus 2.7% (P = 1.00), and 9.4% versus 8.1% (P = .81), respectively. The incidence of major morbidity was higher and statistically significant in group 2 compared with group 1: 23% versus 12.9% (P = .1). Postoperative bronchopleural fistula occurred in 4.7% (4/85) of patients with occult N2 (group 1) and in 10.1% (15/148) of patients undergoing IT (group 2) (P = .10). Median overall survival (OS) was 2.2 years, with a 3 and 5-year OS of 43.4% and 31.6%, respectively. Disease-free survival (DFS) was 1.5 years, with 3 and 5-year DFS of 41.6% and 32%, respectively; no difference in OS and DFS between the 2 groups was found. CONCLUSIONS: Considering the acceptable morbidity and mortality rate and the long-term survival, PN should not be excluded for selected patients with stage IIIA-N2 NSCLC as a matter of principle.

In-depth characterization of congenital Zika syndrome in immunocompetent mice: Antibody-dependent enhancement and an antiviral peptide therapy.

BACKGROUND: Zika virus (ZIKV) infection during pregnancy may cause major congenital defects, including microcephaly, ocular, articular and muscle abnormalities, which are collectively defined as Congenital Zika Syndrome. Here, we performed an in-depth characterization of the effects of congenital ZIKV infection (CZI) in immunocompetent mice. METHODS: Pregnant dams were inoculated with ZIKV on embryonic day 5.5 in the presence or absence of a sub-neutralizing dose of a pan-flavivirus monoclonal antibody (4G2) to evaluate the potential role of antibody-dependent enhancement phenomenon (ADE) during short and long outcomes of CZI. FINDINGS: ZIKV infection induced maternal immune activation (MIA), which was associated with occurrence of foetal abnormalities and death. Therapeutic administration of AH-D antiviral peptide during the early stages of pregnancy prevented ZIKV replication and death of offspring. In the post-natal period, CZI was associated with a decrease in whole brain volume, ophthalmologic abnormalities, changes in testicular morphology, and disruption in bone microarchitecture. Some alterations were enhanced in the presence of 4G2 antibody. INTERPRETATION: Our results reveal that early maternal ZIKV infection causes several birth defects in immunocompetent mice, which can be potentiated by ADE phenomenon and are associated with MIA. Additionally, antiviral treatment with AH-D peptide may be beneficial during early maternal ZIKV infection. FUND: This work was supported by the Brazilian National Science Council (CNPq, Brazil), Minas Gerais Foundation for Science (FAPEMIG), Funding Authority for Studies and Projects (FINEP), Coordination of Superior Level Staff Improvement (CAPES), National Research Foundation of Singapore and Centre for Precision Biology at Nanyang Technological University.