Impact of Non‐PV AF Foci on the Second Catheter Ablation for PAF
Background
Paroxysmal atrial fibrillation (AF) is primarily triggered by pulmonary veins (PVs). However, non‐PV AF foci may also ...trigger AF.
Methods
We examined 207 patients (mean age, 62 ± 11 years; 166 men) who underwent a second catheter ablation (CA) and evaluated the clinical significance of non‐PV AF foci on the outcomes.
Results
Electrical reconnections between the PVs and left atrium (LA) were observed in 162 patients (78.3%). Non‐PV AF foci were identified in 95 patients (45.9%, 60 patients with successfully ablated non‐PV AF foci and 35 with unmappable non‐PV AF foci). During a median follow‐up period of 22.7 months, 61 patients (29.5%; 18/112 16.1% without non‐PV AF foci vs. 20/60 33.3% with successfully ablated non‐PV AF foci vs. 23/35 65.7% with unmappable non‐PV AF foci, P < 0.0001) developed AF recurrence; 52 (85.2%) developed recurrence within 1 year. The presence of non‐PV AF foci was a significant clinical predictor of AF recurrence after the second CA; successfully ablated non‐PV AF foci increased the AF recurrence risk by 2.24 times (95% confidence interval CI, 1.12–4.54; P = 0.02), and unmappable AF foci increased this risk by 5.58 times (95% CI, 2.73–11.63; P < 0.0001).
Conclusion
Nearly half of the patients had non‐PV AF foci at the second CA session. AF recurred after the second CA session in approximately 30%, with most recurrences happening within 1 year. The presence of non‐PV AF foci significantly increased the AF recurrence risk after a second CA. When non‐PV AF foci were unmappable, the AF recurrence rate was extremely high.
To reveal the primary historical events that affected the geographic differentiation in freshwater organisms in the Japanese archipelago, we investigated the phylogeny and phylogeographic structure ...of the widely distributed freshwater fish Pseudogobio esocinus. We conducted comprehensive phylogeographic analyses based on partial sequences of the mitochondrial DNA cytochrome b (cyt b) gene in 1,212 P. esocinus specimens from 201 locations in 136 river systems along with sequence data from related species. We also examined the entire cyt b sequence and three nuclear gene sequences for a subset of individuals to estimate the phylogenetic relationships and divergence times. Historical processes shaping the present phylogeographic patterns were inferred by the Bayesian skyline plot, mismatch distribution and nested clade phylogeographic analyses. The mitochondrial and nuclear DNA phylogenies showed that the Japanese P. esocinus was not monophyletic and consisted of three largely differentiated groups. Divided by the Central Highlands, two groups were distributed in southwestern Japan, with a third group in northeastern Japan. The estimated divergence time indicated that the framework of the present ranges of the three groups was formed during or before the Early Pliocene. In southwestern Japan, the two groups often occurred sympatrically and included several regional subgroups bounded by major mountain systems uplifted in the early Pleistocene, while in the northeastern Japanese group, recent (since about 0.3 million years ago) range expansion from the northwestern area was inferred. The results suggest the importance of the uplifting of the Central Highlands and interconnection with the continental area in the distribution and divergence of P. esocinus, which may have also influenced regional heterogeneity in the Japanese freshwater fauna. The contrasting phylogeographic patterns between northeastern and southwestern Japan probably reflect their topographic and geohistorical differences, and imply differences in the formation process of freshwater fauna between the two regions.
Regulatory T (Treg) cells are important negative regulators of immune homeostasis, but in cancers they tone down the anti-tumor immune response. They are distinguished by high expression levels of ...the chemokine receptor CCR4, hence their targeting by the anti-CCR4 monoclonal antibody mogamulizumab holds therapeutic promise. Here we show that despite a significant reduction in peripheral effector Treg cells, clinical responses are minimal in a cohort of patients with advanced CCR4-negative solid cancer in a phase Ib study (NCT01929486). Comprehensive immune-monitoring reveals that the abundance of CCR4-expressing central memory CD8
T cells that are known to play roles in the antitumor immune response is reduced. In long survivors, characterised by lower CCR4 expression in their central memory CD8
T cells possessed and/or NK cells with an exhausted phenotype, cell numbers are eventually maintained. Our study thus shows that mogamulizumab doses that are currently administered to patients in clinical studies may not differentiate between targeting effector Treg cells and central memory CD8
T cells, and dosage refinement might be necessary to avoid depletion of effector components during immune therapy.
Purpose
As the number of cases of early lung cancer in Japan grows, an analysis of the present status of surgical treatments for clinical stage IA lung cancer using a nationwide database with ...web-based data entry is warranted.
Methods
The operative and perioperative data from 47,921 patients who underwent surgery for clinical stage IA lung cancer in 2014 and 2015 were obtained from the National Clinical Database (NCD) of Japan. Clinicopathological characteristics, surgical procedure, mortality, and morbidity were analyzed, and thoracotomy and video-assisted thoracic surgery (VATS) were compared.
Results
The patients comprised 27,208 men (56.8%) and 20,713 women (43.2%); mean age, 69.3 years. Lobectomy was performed in 64.8%, segmentectomy in 15.2%, and wedge resection in 19.8%. The surgical procedures were thoracotomy in 12,194 patients (25.4%) and a minimally invasive approach (MIA) in 35,727 patients (74.6%). MIA was divided into VATS + mini-thoracotomy (
n
= 13,422, 28.0%) and complete VATS (
n
= 22,305, 46.5%). The overall postoperative mortality rate was 0.4%, being significantly lower in the MIA group than in the thoracotomy group (0.3% vs 0.8%,
P
< 0.001).
Conclusions
Our analysis of data from the NCD indicates that MIA has become the new standard treatment for clinical stage IA lung cancer.
Objective
This study examined the clinical and radiological characteristics of adenocarcinoma having the micropapillary histological subtype.
Methods
We included 233 patients who were operated from ...2001 to 2012 for lung adenocarcinoma of 2 cm or less. The pathology was reviewed according to the 2015 WHO classification. We defined adenocarcinoma with a micropapillary component as adenocarcinoma in which the area of the micropapillary histological subtype exceeded 5% of the tumor. The difference in cumulative incidence of recurrence (CIR) in the presence of death as a competing risk between two groups was assessed using the methods of Gray.
Results
Twenty-one cases (9.0%) had a micropapillary component. The micropapillary component was associated with a higher frequency of lymphatic invasion (28.6 vs. 7.5% in adenocarcinoma without a micropapillary component;
P
= 0.008) and vascular invasion (38.1 vs. 15.1%,
P
= 0.014) and lymph node metastasis (31.3 vs. 5.2%,
P
= 0.003). The median follow-up period was 6.5 years. CIR at 5 years was 23.8% 95% confidence interval (CI), 8.3–43.7% for adenocarcinoma with a micropapillary component, and 11.4% (95% CI, 7.4–16.2%) for adenocarcinoma without a micropapillary component (
P
= 0.033). Adenocarcinoma with a micropapillary component was more frequent in solid nodules (17.8%, 16/90) on high-resolution computed tomography (HRCT) than in either ground-glass nodules (1.5%, 1/67) or part-solid nodules (5.3%, 4/76) (
P
= 0.001). The HRCT finding was the only preoperative factor that was associated with a micropapillary component in the multivariate analysis.
Conclusions
The micropapillary component in adenocarcinoma should be regarded as indicative of a high-grade malignancy and was associated with the HRCT finding.
Background: Whether comprehensive risk assessment predicts post-referral outcome in patients with pulmonary arterial hypertension (PAH) referred for lung transplantation (LT) in Japan is ...unknown.Methods and Results: We retrospectively analyzed 52 PAH patients referred for LT. Risk status at referral was assessed using 3- and 4-strata models from the 2022 European Society of Cardiology and European Respiratory Society guidelines. The 3-strata model intermediate-risk group was further divided into 2 groups based on the median proportion of low-risk variables (modified risk assessment MRA). The primary outcome was post-referral mortality. During follow-up, 9 patients died and 13 patients underwent LT. There was no survival difference among 3-strata model groups. The 4-strata model classified 33, 16, and 3 patients as low intermediate, high intermediate, and high risk, respectively. The 4-strata model identified high-risk patients with a 1-year survival rate of 33%, but did not discriminate survival between the intermediate-risk groups. The MRA classified 15, 28, 8, and 1 patients as low, low intermediate, high intermediate, and high risk, respectively. High intermediate- or high-risk patients had worse survival (P<0.001), with 1- and 3-year survival rates of 64% and 34%, respectively. MRA high intermediate- or high-risk classification was associated with mortality (hazard ratio 12.780; 95% confidence interval 2.583–63.221; P=0.002).Conclusions: Patients classified as high intermediate or high risk by the MRA after treatment should be referred for LT.
Lung transplantation (LT) is the only option for patients with pulmonary arterial hypertension (PAH) refractory to maximal medical therapy. However, some patients referred for LT could survive ...without LT, and its determinants remain unclear. This study aimed to elucidate prognostic factors of severe PAH at the referral time. We retrospectively analyzed 34 patients referred for LT evaluation. The primary outcome was a composite of death or LT. Over a median follow-up period of 2.56 years, eight patients received LT and eight died. Compared with LT-free survival group, pulmonary arterial systolic pressure (PASP) was higher (p = 0.042), and the ratio of tricuspid annular plane systolic excursion (TAPSE) to PASP (TAPSE/PASP) was lower (p = 0.01) in LT or death group. In receiver operating characteristic analysis, the area under the curve was 0.759 (95% confidence interval 0.589-0.929) for TAPSE/PASP to predict primary outcome, and the optimal cut-off value was 0.30 mm/mmHg (sensitivity 0.875 and specificity 0.667). In a multivariate analysis, TAPSE/PASP was independently associated with death or LT. Kaplan-Meier analysis showed a better LT-free survival in patients with TAPSE/PASP ≧0.30 mm/mmHg than in those with < 0.30 mm/mmHg (p = 0.001). Low-level TAPSE/PASP could be a poor prognostic factor in PAH patients referred for LT evaluation.
Abstract
OBJECTIVES: Virtual-assisted lung mapping (VAL-MAP) is a preoperative bronchoscopic multispot dye-marking technique using virtual images. The purpose of this study was to evaluate the ...safety, efficacy and reproducibility of VAL-MAP among multiple centres.
METHODS: Selection criteria included patients with pulmonary lesions anticipated to be difficult to identify at thoracoscopy and/or those undergoing sub-lobar lung resections requiring careful determination of resection margins. Data were collected prospectively and, if needed, compared between the centre that originally developed VAL-MAP and 16 other centres.
RESULTS: Five hundred patients underwent VAL-MAP with 1781 markings (3.6 ± 1.2 marks/patient). Complications associated with VAL-MAP necessitating additional management occurred in four patients (0.8%) including pneumonia, fever and temporary exacerbation of pre-existing cerebral ischaemia. Minor complications included pneumothorax (3.6%), pneumomediastinum (1.2%) and alveolar haemorrhage (1.2%), with similar incidences between the original centre and other centres. Marks were identifiable during operation in approximately 90%, whereas the successful resection rate was approximately 99% in both groups, partly due to the mutually complementary marks. The contribution of VAL-MAP to surgical success was highly rated by surgeons resecting pure ground glass nodules (P < 0.0001), tumours ≤ 5 mm (P = 0.0016), and performing complex segmentectomy and wedge resection (P = 0.0072).
CONCLUSIONS: VAL-MAP was found to be safe and reproducible among multiple centres with variable settings. Patients with pure ground glass nodules, small tumours and resections beyond conventional anatomical boundaries are considered the best candidates for VAL-MAP.
Clinical Trial Registration Number: UMIN 000008031. University Hospital Medical Information Network Clinical Trial Registry (http://www.umin.ac.jp/ctr/).
Spread through air space (STAS) is recognized as a pattern of invasion in lung adenocarcinoma and has been reported to be a predictor of recurrence and survival in patients with early-stage lung ...adenocarcinoma. However, this parameter has not been studied well in stage III (N2) lung adenocarcinoma. In this study, we evaluated the association between STAS invasion patterns and recurrence and survival in stage III (N2) lung adenocarcinoma.
We retrospectively reviewed data from 76 patients at University of Tokyo with stage III (N2) lung adenocarcinoma who underwent surgery from August 1998 to December 2013. Statistical analysis was performed to determine the impact of STAS invasion clinicopathological features and clarify the relationship between this pattern of invasion and survival.
Tumour STAS was observed in 46 of 76 patients (60.5%) and was significantly associated with the presence of lymphatic invasion (P < 0.001), papillary components (P < 0.001) and micropapillary components (P < 0.001). STAS was also significantly associated with recurrence (5-year recurrence-free probability: 19.0% vs 46.1%, P < 0.05). Univariate analyses showed that STAS was a significant risk factor for recurrence (hazard ratio 1.94, 95% confidence interval 1.07-3.51; P = 0.029).
The presence of STAS invasion pattern is a significant risk factor for recurrence in stage III (N2) lung adenocarcinoma.
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