Intraplaque wiring enables drug-coated balloons to be utilized for percutaneous recanalization of chronically occluded coronary arteries.

OBJECTIVES: This study aimed to determine whether drug-coated balloon (DCB) angioplasty following intraplaque wiring and the use of modified balloons is safe and effective in the percutaneous treatment of coronary chronic total occlusions (CTOs). BACKGROUND: DCB is an alternative therapeutic option without the limitations of permanent vascular implants. However, its efficacy in CTOs has yet to be confirmed. The combination of modified balloons and DCB can be effectively applied when the intraplaque passage of the guidewire is achieved in CTOs. METHODS: Data from 124 consecutive CTO lesions (105 patients) treated at our hospital between February 2016 and December 2020 were screened for inclusion and retrospectively analyzed. Among the 118 lesions successfully recanalized, intraplaque wiring was achieved in 108, and 85 were treated by the DCB-only approach following cutting/scoring balloon dilatation. RESULTS: Follow-up data were available for 82 lesions (71 patients). The median occlusion length was 18.5 mm, and the J-CTO score was 1.7 ± 0.9. No in-hospital major adverse cardiac events occurred, including abrupt vessel closure. During the median 29-month follow-up period, target lesion revascularization was performed for 10 lesions. Follow-up coronary angiography (8.7 ± 3.9 months after the index procedure) was performed for 64 lesions, demonstrating late lumen loss of -0.15 mm (interquartile range -0.4 to 0.23 mm), binary restenosis (diameter stenosis ≥50%) in 12 lesions (18.8%), and late lumen enlargement in 37 (57.8%). CONCLUSION: The DCB-only approach following the use of modified balloons is a promising strategy for coronary CTOs when intraplaque wiring is achieved.

A multicenter propensity score-matched analysis of lymphadenectomy in N1-positve lung cancer.

OBJECTIVES: Selective mediastinal lymph node dissection based on lobe-specific metastases is widely recognized in daily practice. However, the significance of mediastinal lymph node dissection for N1-positive tumors has not been elucidated. METHODS: We retrospectively reviewed 359 patients with N1-positive lung cancer who underwent lobectomy with systematic mediastinal lymph node dissection (systematic lymph node dissection) (n = 150) and lobe-specific mediastinal lymph node dissection (lobe-specific lymph node dissection) (n = 209). The operative and postoperative results and their propensity score-matched pairs were compared. The factors affecting survival were assessed using competing risk and multivariable analyses. RESULTS: The cumulative incidence of recurrence and the cumulative incidence of cancer-specific death were not significantly different between systematic and lobe-specific lymph node dissection in entire cohort. In the propensity score-matched cohort (83 pairs), systematic lymph node dissection tended to detect N2 lymph node metastasis more frequently (55.4 vs. 41%, P = 0.087). Eleven patients (13.2%) in the systematic lymph node dissection group had a metastatic N2 lymph node 'in the systematic lymph node dissection field' that lobe-specific lymph node dissection did not dissect. The oncological outcomes between patients undergoing systematic lymph node dissection (5-year cumulative incidence of recurrence, 62.1%; 5-year cumulative incidence of cancer-specific death, 27.9%) and lobe-specific lymph node dissection (5-year cumulative incidence of recurrence, 60.1%; 5-year cumulative incidence of cancer-specific death, 23.3%) were similar. The propensity score-adjusted multivariable analysis for cumulative incidence of recurrence revealed that the prognosis associated with systematic lymph node dissection was comparable with the prognosis with lobe-specific lymph node dissection (hazard ratio, 1.17; 95% confidence interval, 0.82-1.67; P = 0.37). CONCLUSIONS: The extent of lymph node dissection can affect accurate pathological staging; however, it was not associated with survival outcome in the treatment of N1-positive lung cancer.

Clinical Impact of Sarcopenia 1 Year After Surgery for Patients with Early-Stage Non-small Cell Lung Cancer.

BACKGROUND: Sarcopenia is associated with prognostic outcomes for patients with various solid tumors, whereas the clinical significance of sarcopenia 1 year after surgery (post-sarcopenia) for non-small cell lung cancer (NSCLC) has not been investigated. This study aimed to clarify the clinical impact of post-sarcopenia and factors associated with post-sarcopenia in NSCLC patients without preoperative sarcopenia. METHODS: This study enrolled 443 patients with clinical stage 1 or 2 NSCLC (234 patients without preoperative sarcopenia [NS group] and 209 patients with preoperative sarcopenia [S group]) who underwent computed tomography (CT) at two time points (before surgery and a year afterward) or more. The study assessed CT images at the L3 level to calculate the psoas muscle area index (PAI). The PAI cutoff value for sarcopenia was defined as 6.36 cm2/m2 for the men and 3.92 cm2/m2 for the women. RESULTS: In the NS group, the diagnosis for 40.1% of the women and 52.6% of the men was post-sarcopenia (NS-S group). The overall survival (OS) for the S and NS-S cohorts was worse than for the non-sarcopenic patients before and after surgery (p < 0.001 and p = 0.017, respectively). In the multivariable analysis, sarcopenia, either before or after surgery (hazard ratio, 3.272; p = 0.002), in the NS group was independently associated with OS, whereas the factors associated with post-sarcopenia were male sex (p = 0.002), aging (p < 0.001), and low body mass index (p < 0.001). CONCLUSIONS: Sarcopenia, either before or after surgery, is prognostic in early-stage NSCLC. Male sex, aging, and low body mass index (BMI) are associated with post-sarcopenia.

Radiomics with Artificial Intelligence for the Prediction of Early Recurrence in Patients with Clinical Stage IA Lung Cancer.

BACKGROUND: We seek to explore the ability of computed tomography (CT)-based radiomics coupled with artificial intelligence (AI) to predict early recurrence (< 2 years after surgery) in patients with clinical stage 0-IA non-small cell lung cancer (c-stage 0-IA NSCLC). PATIENTS AND METHODS: Data of 642 patients were collected for early recurrence and assigned to the derivation and validation cohorts at a ratio of 2:1. Using the AI software Beta Version (Fujifilm Corporation, Japan), 39 AI imaging factors, including 17 factors from the AI ground-glass nodule analysis and 22 radiomic features from nodule characterization analysis, were extracted. RESULTS: Multivariate analysis showed that male sex (p = 0.016), solid part size (p < 0.001), CT value standard deviation (p = 0.038), solid part volume ratio (p = 0.016), and bronchus translucency (p = 0.007) were associated with recurrence-free survival (RFS). Receiver operating characteristics analysis showed that the area under the curve and optimal cutoff values relevant to recurrence were 0.707 and 1.49 cm for solid part size, and 0.710 and 22.9% for solid part volume ratio, respectively. The 5-year RFS rates for patients in the validation set with solid part size ≤ 1.49 cm and > 1.49 cm were 92.2% and 70.4% (p < 0.001), whereas those for patients with solid part volume ratios ≤ 22.9% and > 22.9% were 97.8% and 71.7% (p < 0.001), respectively. CONCLUSIONS: CT-based radiomics coupled with AI contributes to the noninvasive prediction of early recurrence in patients with c-stage 0-IA NSCLC.

Laser vaporization of atherothrombotic burden before drug-coated balloon application in ST-segment elevation myocardial infarction: Two-year outcomes of the laser-DCB trial.

OBJECTIVES: This study aimed to examine whether the combination of excimer laser coronary atherectomy (ELCA) and drug-coated balloon (DCB) angioplasty can provide feasible clinical outcome in patients with ST-segment elevation myocardial infarction (STEMI) with 8-month and 2-year scheduled follow-up angiography. BACKGROUND: Intracoronary thrombus elevates the risk of interventional treatment in patients with STEMI and hampers drug absorption into the vasculature released from DCB. METHODS: Sixty-two patients with STEMI within 24 h after the onset of symptoms were enrolled in this prospective, single-center, single-arm study. RESULTS: The laser catheter was successfully crossed distal to the culprit lesion in all cases. No ELCA-related adverse events occurred. Bail-out stenting was required in two patients (3.2%) after adjunctive ballooning; thus, the remaining 60 patients were completed with DCB angioplasty without stenting. Scheduled angiography at 8 months and 2 years was completed in 100% and 85.2%, respectively, and minimal lumen diameters were 3.4 ± 0.5, 3.4 ± 0.6, and 3.4 ± 0.5 mm after the procedure, at 8 months and at 2 years, respectively. Binary restenosis was observed in five patients (8.1%) in whom target lesion revascularization was performed. The duration of dual antiplatelet therapy was 2.3 ± 2.2 months, and neither abrupt vessel closure, reinfarction, cardiac death nor major bleeding was observed. CONCLUSION: A combination of DCB angioplasty with ELCA is a feasible therapeutic option for STEMI.

Prognostic Significance of Ground-Glass Opacity Components in 5-Year Survivors With Resected Lung Adenocarcinoma.

BACKGROUND: Reports on the prognosis for 5-year survivors with lung adenocarcinoma after resection are sparse. This study aimed to identify factors associated with overall survival (OS) and cancer-specific survival (CSS) for 5-year survivors with completely resected lung adenocarcinoma, and to determine whether preoperative imaging factors, including the presence of ground-glass opacity (GGO) components, affect late recurrence in long-term survivors. METHODS: Complete resection of lung adenocarcinoma was performed for 1681 patients between January 2000 and December 2013. Of these patients, 936 who survived 5 years or longer after surgery were identified, and factors associated with OS and CSS were determined using the Cox proportional hazard model. RESULTS: Multivariable analysis demonstrated that lymph node metastasis (p < 0.01) and absence of GGO components (p < 0.01) were independently associated with OS and CSS for the 5-year survivors. The absence of GGO components was significantly associated with OS (p < 0.01) and CSS (p < 0.01) also for the 5-year survivors with stage 1 disease (n = 782) and for the 5-year survivors without recurrence (n = 809). The incidence of recurrence anytime during the 10-year postoperative follow-up period differed significantly between the 5-year survivors with and without GGO components. CONCLUSIONS: The absence of GGO components was significantly associated with an unfavorable prognosis for the 5-year survivors with completely resected lung adenocarcinoma regardless whether they had recurrences not.

Systematic Versus Lobe-Specific Mediastinal Lymphadenectomy for Hypermetabolic Lung Cancer.

BACKGROUND: The optimal extent of lymph node dissection (LND) for hypermetabolic tumors that are associated with high rates of nodal disease, recurrence, or mortality has not been elucidated. METHODS: We reviewed 375 patients who underwent lobectomy with lymphadenectomy for clinical T2-3 N0-1 M0 hypermetabolic non-small cell lung cancer (NSCLC) [maximum standard uptake value (SUVmax) ≥ 6.60] via a multicenter database. Extent of LND was classified into systematic mediastinal LND (systematic LND) and lobe-specific mediastinal LND (lobe-specific LND). Postoperative outcomes after lobectomy with systematic LND (n = 128) and lobe-specific LND (n = 247) were analyzed for all patients and their propensity-score-matched pairs. RESULTS: Cancer-specific survival (CSS) and recurrence-free interval (RFI) of the systematic LND group were not significantly different from those of the lobe-specific LND group in the nonadjusted whole cohort. In the propensity-score-matched cohort (101 pairs), systematic LND dissected significantly more lymph nodes (20.0 versus 16.0 nodes, P = 0.0057) and detected lymph node metastasis more frequently (53.5% vs. 33.7%, P = 0.0069). Six (5.9%) patients in the systematic LND group had a metastatic N2 lymph node "in the systematic LND field" that lobe-specific LND could not dissect. The systematic LND group tended to have better prognosis than the lobe-specific LND group (5-year CSS rates, 82.6% versus 69.6%; 5-year RFI rates, 56.6% vs. 47.3%). CONCLUSIONS: Systematic LND was found to harvest more metastatic lymph nodes and provide better oncological outcome than lobe-specific LND in a cohort of hypermetabolic NSCLC patients.

Laser Vaporization of Intracoronary Thrombus and Identifying Plaque Morphology in ST-Segment Elevation Myocardial Infarction as Assessed by Optical Coherence Tomography.

OBJECTIVES: We evaluated the thrombus-vaporizing effect of excimer laser coronary angioplasty (ELCA) in patients with ST-segment elevation myocardial infarction (STEMI) by optical coherence tomography (OCT). BACKGROUND: Larger intracoronary thrombus elevates the risk of interventional treatment and mortality in patients with STEMI. METHODS: A total of 92 patients with STEMI who presented within 24 hours from the onset and underwent ELCA following manual aspiration thrombectomy (MT) were analyzed. RESULTS: The mean baseline thrombolysis in myocardial infarction flow grade was 0.4 ± 0.6, which subsequently improved to 2.3 ± 0.7 after MT (p < 0.0001) and 2.7 ± 0.5 after ELCA (p=0.0001). The median residual thrombus volume after MT was 65.7 mm3, which significantly reduced to 47.5 mm3 after ELCA (p < 0.0001). Plaque rupture was identified by OCT in only 22 cases (23.9%) after MT, but was distinguishable in 36 additional cases after ELCA (total: 58 cases; 63.0%). Ruptured lesions contained a higher proportion of red thrombus than nonruptured lesions (75.9% vs. 43.3%, p=0.001). Significantly larger thrombus burden after MT (69.6 mm3 vs. 56.3 mm3, p < 0.05) and greater thrombus reduction by ELCA (21.2 mm3 vs. 11.8 mm3, p < 0.01) were observed in ruptured lesions than nonruptured lesions. CONCLUSIONS: ELCA effectively vaporized intracoronary thrombus in patients with STEMI even after MT. Lesions with plaque rupture contained larger thrombus burden that was frequently characterized by red thrombus and more effectively reduced by ELCA.

The Correlation Between Fissureless Technique and Prolonged Air Leak for Patients Undergoing Video-Assisted Right Upper Lobectomy.

PURPOSE: We aimed to assess the clinical usefulness of the fissureless technique, which avoided dissection of the lung parenchyma over the pulmonary artery, in preventing prolonged air leak after video-assisted thoracic surgery right upper lobectomy (VATS RUL). METHODS: Perioperative outcomes, including the frequency of prolonged air leak after fissureless technique or traditional fissure dissection technique, which dissected the lung parenchyma through the fissure, were compared in patients who underwent VATS RUL (n = 213) between January 2016 and March 2020. We adopted our fissural grade to evaluate the degree of fused fissure ranging from II (light incomplete fissure) to IV (severe incomplete fissure), which covered all fissural grades in 213 patients. RESULTS: Fifty-four and 159 patients underwent fissureless and traditional techniques, respectively. Significant differences in the incidence of prolonged air leak (p = 0.037), time to air leak cessation (p = 0.047), and duration of chest tube placement (p = 0.017) were observed between fissureless and traditional technique groups. On multivariable analysis, traditional technique (p = 0.005), and greater fissural grade (III vs II, p = 0.020; IV vs II, p = 0.001) were significantly associated with prolonged air leak. CONCLUSIONS: Fissureless technique during VATS RUL can be a superior alternative to the traditional technique to prevent prolonged air leak in treating incomplete fissures.

Powered articulation by the SigniaTM stapling system for stapling position adjustments: optimizing safe surgical margins in thoracoscopic sublobar resection.

Accumulation of experience and advances in techniques and instruments have enabled surgeons to perform video-assisted thoracic surgery (VATS) safely for sublobar resection, including segmentectomy and wedge resection. A key to successful VATS sublobar resection is to have adequate resection margins and the appropriate use of articulated surgical staplers is essential for this purpose. The SigniaTM stapling system (Covidien Japan, Tokyo) has been used extensively in the fields of thoracic surgery. Its features include high maneuverability with fully powered articulation, rotation, clamping, and firing, which the surgeon can control with one hand. We introduce the "sliding technique" using the SigniaTM system, which allows for adjustment of the resection lines of the pulmonary parenchyma to optimize safe surgical margins with minimal stapler movement, and without repetitively moving the stapler in and out of the pleural cavity, during VATS sublobar resection.

Ubiquitin C-terminal hydrolase-L1 has prognostic relevance and is a therapeutic target for high-grade neuroendocrine lung cancers.

High-grade neuroendocrine lung cancer (HGNEC), which includes small cell lung cancer (SCLC) and large cell neuroendocrine carcinoma (LCNEC) of the lung is a rapidly proliferating, aggressive form of lung cancer. The initial standard chemotherapeutic regimens of platinum doublets are recommended for SCLC and have been frequently used for LCNEC. However, there are currently no molecularly targeted agents with proven clinical benefit for this disease. The deubiquitinating enzyme ubiquitin C-terminal hydrolase-L1 (UCHL1) is a neuroendocrine cell-specific product that is known as a potential oncogene in several types of cancer, but little is known about the biological function of UCHL1 and its therapeutic potential in HGNEC. In this study, we found that preclinical efficacy evoked by targeting UCHL1 was relevant to prognosis in HGNEC. UCHL1 was found to be expressed in HGNEC, particularly in cell lines and patient samples of SCLC, and the combined use of platinum doublets with selective UCHL1 inhibitors improved its therapeutic response in vitro. Immunohistochemical expression of UCHL1 was significantly associated with postoperative survival in patients with HGNEC and contributed towards distinguishing SCLC from LCNEC. Circulating extracellular vesicles (EV), including exosomes isolated from lung cancer cell lines and serum from early-stage HGNEC, were verified by electron microscopy and nanoparticle tracking analysis. Higher levels of UCHL1 mRNA in EV were found in the samples of patients with early-stage HGNEC than those with early-stage NSCLC and healthy donors' EV. Taken together, UCHL1 may be a potential prognostic marker and a promising druggable target for HGNEC.

Phosphorus-Recycling Wittig Reaction: Design and Facile Synthesis of a Fluorous Phosphine and Its Reusable Process in the Wittig Reaction.

This study shows that phosphorus sources can be recycled using the appropriate fluorous phosphine in the Wittig reaction. The designed fluorous phosphine, which has an ethylene spacer between its phosphorus atom and the perfluoroalkyl group, was synthesized from air-stable phosphine reagents. The synthesized phosphine can be used for the Wittig reaction process to obtain various alkenes in adequate yields and stereoselectivity. The concomitantly formed fluorous phosphine oxide was extracted from the reaction mixture using a fluorous biphasic system. The fluorous phosphine was regenerated by reducing the fluorous phosphine oxide with diisobutylaluminum hydride. Finally, a series of gram scale phosphorus recycling processes were performed, which included the Wittig reaction, separation, reduction, and reuse.

Randomized comparison between 2-link cell design biolimus A9-eluting stent and 3-link cell design everolimus-eluting stent in patients with de novo true coronary bifurcation lesions: the BEGIN trial.

The appropriate stent platform for treating coronary bifurcation lesions (CBLs) remains controversial. Previous bench tests have demonstrated the superiority of a 2-link cell design to 3-link cell design for creating inter-strut dilation at the side branch ostium. This randomized multicenter prospective BEGIN trial compared the biodegradable polymer-based biolimus A9-eluting stent (2-link BES) with the durable polymer-based cobalt chromium everolimus-eluting stent (3-link EES) in 226 patients with de novo CBLs. Patients with true bifurcations, defined as > 50% stenosis in the main vessel and side branch (SB) and an SB diameter > 2.25 mm, were enrolled. Guide wire re-crossing to the distal cell (near the carina) in the jailed SB and final kissing inflation were recommended. The SB angiographic endpoint was < 50% stenosis diameter. Left-main CBLs (13.5% vs. 13.0%) and 2-stent technique (30.6% vs. 22.6%) rates were similar. The primary endpoints (minimum lumen diameter at the SB ostium measured at an independent core laboratory at the 8-month follow-up) were comparable (1.64 ± 0.50 mm vs. 1.63 ± 0.51 mm, p = 0.976). There was no significant difference in composite outcomes of cardiac death, myocardial infarction, or target vascular revascularization at 12 months (7.4% vs. 8.0%, p = 0.894). Two-link BES and 3-link EES showed similar 8-month angiographic and 1-year clinical outcomes for true CBLs.

Efficacy of Cutting Balloon Angioplasty for Chronic Total Occlusion of Femoropopliteal Arteries.

BACKGROUND: Chronic total occlusion (CTO) of femoropopliteal artery (FP) continues to be a lesion subset where maintaining long-term patency after endovascular treatment is challenging. We evaluated the efficacy of cutting balloon angioplasty (CBA) for de novo FP-CTOs in patients with symptomatic lower limb ischemia. METHODS: Seventy-three limbs of 67 symptomatic patients with de novo FP-CTOs successfully recanalized using CBA alone were enrolled in this study. Primary patency was defined as the absence of recurrent symptoms and no deterioration of the ankle-brachial index (ABI) >0.10 from the immediate postinterventional value. RESULTS: The mean age was 73.5 ± 7.3 years, and 59.7% of patients had diabetes mellitus. Most lesions were classified as Trans-Atlantic Inter-Society Consensus II type C (n = 18; 24.7%) or type D (n = 44; 60.3%), with mean lesion and occluded lengths of 24.8 ± 11.4 and 17.8 ± 11.2 cm, respectively. No procedure-related adverse events occurred, except one distal embolization. The ABI significantly increased after intervention from 0.52 ± 0.12 to 0.80 ± 0.15 (P < 0.0001), with marked improvement in clinical symptoms (Rutherford stage: 2.7 ± 1.0 to 1.1 ± 1.2, P < 0.0001). The mean follow-up period was 31.2 ± 18.0 months, and the primary patency rates at 12 and 24 months were 75.3% and 60.6%, respectively. The independent predictive factors of failed patency were baseline hemoglobin A1c (P = 0.031, hazard radio [HR] 1.51 per 1%), occluded length ≥15 cm (P = 0.036, HR 2.90), and severe dissection (P = 0.033, HR 2.85). Vessel calcification and diameter did not affect primary patency. CONCLUSIONS: CBA is a feasible option for endovascular treatment of FP-CTOs. Diabetic status, occlusion length, and severe dissection after CBA are independent negative predictors of long-term patency.