iATT liver fat quantification for steatosis grading by referring to MRI proton density fat fraction: a multicenter study.

BACKGROUND: Several preliminary reports have suggested the utility of ultrasound attenuation coefficient measurements based on B-mode ultrasound, such as iATT, for diagnosing steatotic liver disease. Nonetheless, evidence supporting such utility is lacking. This prospective study aimed to investigate whether iATT is highly concordant with magnetic resonance imaging (MRI)-based proton density fat fraction (MRI-PDFF) and could well distinguish between steatosis grades. METHODS: A cohort of 846 individuals underwent both iATT and MRI-PDFF assessments. Steatosis grade was defined as grade 0 with MRI-PDFF < 5.2%, grade 1 with 5.2% MRI-PDFF < 11.3%, grade 2 with 11.3% MRI-PDFF < 17.1%, and grade 3 with MRI-PDFF of 17.1%. The reproducibility of iATT and MRI-PDFF was evaluated using the Bland-Altman analysis and intraclass correlation coefficients, whereas the diagnostic performance of each steatosis grade was examined using receiver operating characteristic analysis. RESULTS: The Bland-Altman analysis indicated excellent reproducibility with minimal fixed bias between iATT and MRI-PDFF. The area under the curve for distinguishing steatosis grades 1, 2, and 3 were 0.887, 0.882, and 0.867, respectively. A skin-to-capsula distance of ≥ 25 mm was identified as the only significant factor causing the discrepancy. No interaction between MRI-logPDFF and MRE-LSM on iATT values was observed. CONCLUSIONS: Compared to MRI-PDFF, iATT showed excellent diagnostic accuracy in grading steatosis. iATT could be used as a diagnostic tool instead of MRI in clinical practice and trials. Trial registration This study was registered in the UMIN Clinical Trials Registry (UMIN000047411).

Surgical Treatment Outcomes of Patients with Non-Small Cell Lung Cancer and Lymph Node Metastases.

This study aimed to investigate the appropriate subgroups for surgery and adjuvant chemotherapy in patients with non-small-cell lung cancer (NSCLC) and nodal metastases. We retrospectively reviewed 210 patients with NSCLC and nodal metastases who underwent surgery and examined the risk factors for poor overall survival (OS) and recurrence-free probability (RFP) using multivariate Cox proportional hazards analysis. Pathological N1 and N2 were observed in 114 (52.4%) and 96 (47.6%) patients, respectively. A single positive node was identified in 102 patients (48.6%), and multiple nodes were identified in 108 (51.4%). Multivariate analysis revealed that vital capacity < 80% (hazard ratio [HR]: 2.678, 95% confidence interval [CI]: 1.483-4.837), radiological usual interstitial pneumonia pattern (HR: 2.321, 95% CI: 1.506-3.576), tumor size > 4.0 cm (HR: 1.534, 95% CI: 1.035-2.133), and multiple-node metastases (HR: 2.283, 95% CI: 1.517-3.955) were significant independent risk factors for poor OS. Tumor size > 4.0 cm (HR: 1.780, 95% CI: 1.237-2.562), lymphatic permeation (HR: 1.525, 95% CI: 1.053-2.207), and multiple lymph node metastases (HR: 2.858, 95% CI: 1.933-4.226) were significant independent risk factors for recurrence. In patients with squamous cell carcinoma (n = 93), there were no significant differences in OS or RFP between those who received platinum-based adjuvant chemotherapy (n = 25) and those who did not (n = 68), at p = 0.690 and p = 0.292, respectively. Multiple-node metastases were independent predictors of poor OS and recurrence. Patients with NSCLC and single-node metastases should be considered for surgery despite N2 disease. Additional treatment with platinum-based adjuvant chemotherapy may be expected, especially in patients with squamous cell carcinoma.

[Analysis of Surgical Margin Recurrence Following Segmentectomy for Early-stage Non-small Cell Lung Cancer].

BACKGROUND: Surgical margin recurrence following segmentectomy is a critical issue because it may have been avoided by lobectomy. METHODS: Between January 2000 and December 2018, we retrospectively investigated 199 patients who underwent segmentectomy for c-StageⅠ non-small cell lung cancer at our hospital. RESULTS: Recurrence occurred in 20 cases, of which 3 cases had surgical margin recurrence. In our previous study, the recurrence risk factor after segmentectomy was radiologic solid tumor size( cut-off value 1.5 cm). Of the 130 patients in the low-risk group with radiologic solid tumor size of less than 1.5 cm, five had any recurrence, three of which had surgical margin recurrence. In the high-risk group with radiologic solid tumor size of 1.5 cm or more, no surgical margin recurrence was observed. Three cases of surgical margin recurrence were accompanied by lepidic components, and the tumors were difficult to identify intraoperatively and were located close to adjacent areas. CONCLUSION: Surgical margin recurrence may be avoided by carefully considering the segments to be resected and improving the method for identifying the intersegmental plane.

Intra-individual comparison of liver stiffness measurements by magnetic resonance elastography and two-dimensional shear-wave elastography in 888 patients.

PURPOSE: Quantitative elastography methods, such as ultrasound two-dimensional shear-wave elastography (2D-SWE) and magnetic resonance elastography (MRE), are used to diagnose liver fibrosis. The present study compared liver stiffness determined by 2D-SWE and MRE within individuals and analyzed the degree of agreement between the two techniques. METHODS: In total, 888 patients who underwent 2D-SWE and MRE were analyzed. Bland-Altman analysis was performed after both types of measurements were log-transformed to a normal distribution and converted to a common set of units using linear regression analysis for differing scales. The expected limit of agreement (LoA) was defined as the square root of the sum of the squares of 2D-SWE and MRE precision. The percentage difference was expressed as (2D-SWEMRE)/ mean of the two methods×100. RESULTS: A Bland-Altman plot showed that the bias and upper and lower LoAs (ULoA and LLoA) were 0.0002 (95% confidence interval [CI], -0.0057 to 0.0061), 0.1747 (95% CI, 0.1646 to 0.1847), and -0.1743 (95% CI, -0.1843 to -0.1642), respectively. In terms of percentage difference, the mean, ULoA, and LLoA were -0.5944%, 19.8950%, and -21.0838%, respectively. The calculated expected LoA was 17.1178% (95% CI, 16.6353% to 17.6002%), and 789 of 888 patients (88.9%) had a percentage difference within the expected LoA. The intraclass correlation coefficient of the two methods indicated an almost perfect correlation (0.8231; 95% CI, 0.8006 to 0.8432; P<0.001). CONCLUSION: Bland-Altman analysis demonstrated that 2D-SWE and MRE were interchangeable within a clinically acceptable range.

Intra-individual Comparisons of the Ultrasound-Guided Attenuation Parameter and the Magnetic Resonance Imaging-Based Proton Density Fat Fraction Using Bias and Precision Statistics.

Ultrasound-based techniques using the attenuation coefficient, including the ultrasound-guided attenuation parameter (UGAP), have been developed for the quantification of hepatic steatosis. The magnetic resonance imaging-based proton density fat fraction (MRI-PDFF) is considered to be more accurate than liver biopsy for liver fat quantification. The aim of this study was to perform intra-individual comparisons of UGAP and MRI-PDFF for determining hepatic steatosis grade. The study enrolled 309 patients who underwent UGAP and MRI-PDFF measurements. Bland-Altman analysis was conducted after transforming MRI-PDFF values to a normal distribution and converted to a common set of units using linear regression analysis for differing scales. The expected limits of agreement (LOA) was defined as the square root of the sum of the squares of UGAP and MRI-PDFF precision. A Bland-Altman plot revealed that the bias and upper and lower LOAs (ULOA and LLOA) were -0.0047, 0.1160 and -0.1255, respectively. The percentage difference indicated that the mean, ULOA and LLOA were -1.1434%, 18.1723% and -20.4590%, respectively. The calculated expected LOA was 18.5449%, and 283 of 309 patients (91.6%) had a percentage difference within 18.5449%. Bland-Altman analysis revealed that UGAP and MRI-PDFF were interchangeable within a clinically acceptable range.

Maximum Standardized Uptake Value on Positron Emission Tomography is Associated With More Advanced Disease and High-risk Features in Lung Adenocarcinoma.

18F-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (FDG-PET/CT) has been widely used for preoperative staging of lung adenocarcinomas. The aim of this study was to determine whether a high maximum standardized uptake value (SUVmax) could correlate with pathological characteristics in those patients. We retrospectively reviewed patients with clinical stage 0-IA lung adenocarcinoma who underwent preoperative 18F-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography followed by curative anatomical resection. To identify more advanced disease and high-risk features, representing visceral pleural involvement, pulmonary metastasis, lymph node involvement, and lymphovascular involvement in resected surgical specimens, univariate and multivariate logistic regression analyses were performed. The optimal cutoff point for the SUVmax was determined by receiver operating characteristic analysis. In 2 groups divided according to the cutoff point, the disease-free survivals were calculated and compared using the Kaplan-Meier method and the log-rank test. More advanced disease and high-risk features were identified in 55 (18.9%) of the 291 patients. SUVmax was significantly correlated with more advanced disease and high-risk features, as did the consolidation/tumor ratio on computed tomography. Only 2 (1.2%) of the 169 patients with a SUVmax <3.20 showed more advanced disease and high-risk features, compared with 43.4% of patients with a SUVmax ≥3.20. The disease-free survival was significantly higher in patients with a SUVmax <3.20 than in those with a SUVmax ≥3.20 (P = 0.002). A high SUVmax correlates with more advanced disease and high-risk features in patients with clinical stage 0-IA lung adenocarcinoma. The SUVmax should be considered when deciding treatment strategy in early-stage lung adenocarcinoma.

Renal function in Japanese HIV-1-positive patients who switch to tenofovir alafenamide fumarate after long-term tenofovir disoproxil fumarate: a single-center observational study.

BACKGROUND: Tenofovir disoproxil fumarate (TDF) has a strong antiviral effect, but TDF is known to cause renal dysfunction. Therefore, we are investigating preventing renal dysfunction by replacing TDF with tenofovir alafenamide fumarate (TAF), which is known to be relatively safe to the kidneys. However, the changes in renal function under long-term use of TAF are not known. In this study, we evaluated renal function in Japanese HIV-1-positive patients switching to TAF after long-term treatment with TDF. METHODS: A single-center observational study was conducted in Japanese HIV-1-positive patients. TDF was switched to TAF after at least 48 weeks of the treatment so we could evaluate the long-term use of TDF. The primary endpoint was the estimated glomerular filtration rate (eGFR) at 144 weeks of TAF administration. In addition, we predicted the factors that would lead to changes in eGFR after long-term use of TAF. RESULTS: Of the 125 HIV-1-positive patients who were prescribed TAF at our hospital during the study period, 70 fulfilled the study criteria. The eGFR at the time of switching from TDF to TAF was 81.4 ± 21.1 mL/min/1.73 m2. eGFR improved significantly after 12 weeks of taking TAF but significantly decreased at 96 and 144 weeks. The factors significantly correlated with the decrease in eGFR at 144 weeks on TAF were eGFR and weight at the start of TAF. CONCLUSIONS: In this study, it was confirmed that switching to TAF was effective for Japanese HIV-1-positive patients who had been taking TDF for a long period of time and had a reduced eGFR. It was also found that the transition status depended on the eGFR and weight at the time of switch. Since HIV-1-positive patients in Japan are expected to continue taking TAF for a long time, renal function and body weight should be carefully monitored.

Surgical outcomes of ipsilateral metachronous second primary lung cancer.

OBJECTIVES: The optimal surgical approach for metachronous second primary lung cancer (MSPLC), especially ipsilateral MSPLC, remains unclear. This study aimed to review postoperative complications and examine surgical outcomes based on the extent of resection after surgery for ipsilateral MSPLC. METHODS: Clinical data from 61 consecutive patients who underwent pulmonary resection for ipsilateral MSPLC according to the Martini-Melamed criteria between January 2005 and December 2017 in 3 institutes were retrospectively reviewed. RESULTS: Postoperative complications were identified in 12 patients (19.7%). Regarding the combination of initial and second surgery, intraoperative bleeding was significantly greater in patients with anatomic-anatomic resection than in others (P < 0.001). Operation time was significantly longer in patients with anatomic-anatomic resection than in others (P < 0.001). However, postoperative complications showed no significant differences based on the combination of surgeries. Five-year overall survival rates in patients with anatomic resection and wedge resection after second surgery were 75.8% and 75.8%, respectively (P = 0.738), and 5-year recurrence-free survival rates were 54.2% and 67.6%, respectively (P = 0.368). Cox multivariate analysis identified ever-smoker status (P = 0.029), poor performance status (P = 0.011) and tumour size >20 mm (P = 0.001) as independent predictors of poor overall survival, while ever-smoker status (P = 0.040) and tumour size >20 mm (P = 0.007) were considered independent predictors of poor recurrence-free survival. CONCLUSIONS: Regarding postoperative and long-term outcomes for patients with ipsilateral MSPLC, surgical intervention is safe and offers good long-term survival. Wedge resection is an acceptable provided tumours ≤2 cm and ground-glass opacity-predominant as a second surgery for early-stage ipsilateral MSPLC.

Detection of circulatory disturbance after pulmonary vein division during a living donor lobectomy.

Indocyanine green (ICG) is widely used during thoracic surgery to enhance visualization, allowing assessment of the intersegmental plane based on intrapulmonary blood flow (Travis et al. in Ann Thorac Surg 108(2):363-369, 2019; Seshiru et al. in Gen Thorac Cardiovasc Surg 66(2):81-90, 2018). Using ICG to detect blood flow disruption after lung resection, however, has not been addressed. We therefore report a case in which the left lingular pulmonary vein was incidentally divided during left lower lobectomy in a living-lung donor. Intraoperative ICG-enhanced near-infrared fluoroscopic imaging to assess intrapulmonary blood flow detected the problem. We thus avoided potential postoperative residual lung complications in this patient.

Impact of postoperative complications on outcomes of second surgery for second primary lung cancer.

PURPOSE: The best surgical approach for second primary lung cancer remains a subject of debate. The purpose of this study was to review the postoperative complications after second surgery for second primary lung cancer and to investigate the outcomes based on these complications. METHODS: The clinical data of 105 consecutive patients who underwent pulmonary resection for multiple primary lung cancers between January, 1996 and December, 2017, were reviewed according to the Martini-Melamed criteria. RESULTS: After the second surgery, low body mass index (BMI) (< 18.5 kg/m2) (P = 0.004) and high Charlson comorbidity index (CCI) (P = 0.002) were independent predictors of postoperative complications. Survival analysis revealed the 5-year overall survival rates of 74.5% and 61.4% for patients without postoperative complications and those with postoperative complications (P = 0.044), respectively, but the 5-year cancer-specific survival rates of 82.5% and 80.0% (P = 0.926), respectively. During this period, there were significantly more respiratory-related deaths of patients with complications than of those without complications (P = 0.011). CONCLUSION: Surgical intervention is feasible and potentially effective for second primary lung cancer but may not achieve positive perioperative and long-term outcomes for patients with a low BMI or a high CCI. Treatment options should be considered carefully for these patients.

A simple scoring method to predict augmented renal clearance in haematologic malignancies.

WHAT IS KNOWN AND OBJECTIVE: Augmented renal clearance (ARC; hyperfiltration with over 130 mL/min/1.73 m2 of creatinine clearance (CLcr )) commonly occurs in critically ill patients. Recent reports indicate that ARC also occurs in haematologic malignancies. However, the risk factors for ARC in haematologic malignancies remain unknown, and there is no established method to predict ARC in haematologic malignancies. Our objective was to explore the risk factors for ARC retrospectively and develop a scoring method to predict ARC. METHODS: A single-centre, retrospective, observational cohort study was conducted at the Sendai Medical Center (Sendai, Japan); 133 patients (April 2017-March 2019) and 41 patients (April-November 2019) with haematopoietic tumours who were administered vancomycin were enrolled in the analysis and validation cohorts, respectively. To define ARC, we calculated the vancomycin serum concentration when CLcr  = 130 mL/min/1.73 m2 using a one-compartment model. Patients with ARC were defined as those whose actual concentration of vancomycin remained lower than the calculated concentration. Using the analysis cohort, we explored risk factors of ARC and developed a scoring method to predict ARC in haematologic malignancies. The reproducibility of the scoring system was demonstrated using the validation cohort. RESULTS AND DISCUSSION: Through multivariate analysis, young age (P < .001), leukaemia (P = .001) and low serum creatinine (P < .001) were identified as risk factors. According to this result, we established the ARC detection method: age ≤ 50 years = 3 points, 50 years < age ≤65 years = 1 point, leukaemia = 2 points, low SCr = 2 points; patients scoring ≥ 5 points represent the ARC high-risk group. Using this scoring system, we could detect ARC with a sensitivity and specificity of 60.0% and 89.7% in the analysis cohort and 90.0% and 90.9% in the validation cohort, respectively. WHAT IS NEW AND CONCLUSION: Our scoring method could predict ARC in haematologic malignancies and is useful as a simple screening tool for ARC.

Characteristics and risk factors of recurrence in clinical stage I non-small cell lung cancer patients undergoing anatomic segmentectomy.

OBJECTIVE: Although lobectomy is the standard surgical procedure for small-sized non-small cell lung cancer (NSCLC), segmentectomy has been performed for various reasons. The aim of this study was to investigate the characteristics of and risk factors for recurrence in early-stage NSCLC patients undergoing segmentectomy. METHODS: We retrospectively reviewed 179 patients with clinical stage I NSCLC who underwent segmentectomy. Preoperative factors were analyzed using the log-rank test for univariate analyses. Multivariate analyses were performed using a Cox proportional hazards regression model to identify independent risk factors for recurrence. For the significant factors, optimal cutoff points were determined by receiver operating characteristic (ROC) analysis. RESULTS: During the follow-up period of 51 months, 18 patients developed recurrence; 5 had locoregional (including 2 with margin recurrences only), 9 had distant, and 4 had both locoregional and distant recurrence. Multivariate and ROC analysis identified radiologic solid tumor size with a cutoff point of 1.5 cm as an independent risk factor for recurrence. Three patients in the solid size < 1.5 cm group (n = 119) developed recurrence, 2 of whom had surgical margin recurrence, compared to 15 patients in the solid size ≥ 1.5 cm group (n = 60). CONCLUSIONS: The indication for segmentectomy should be decided upon with caution, and the segments to be resected should be carefully considered to secure an appropriate surgical margin in this low-risk subgroup of patients because they may have a relatively higher risk of surgical margin recurrence, despite being at decreased risk.

Living-donor single-lobe lung transplantation for pulmonary hypertension due to alveolar capillary dysplasia with misalignment of pulmonary veins.

This is a case report of a successful single-lobe lung transplantation for pulmonary hypertension secondary to alveolar capillary dysplasia with misalignment of pulmonary veins (ACD/MPV). A 6-year-old boy underwent living-donor single-lobe transplantation with the right lower lobe from his 31-year-old mother. The pretransplantation graft size matching was acceptable: the estimated graft forced vital capacity (FVC) was 96.5% of the recipient's predicted FVC, and the graft size measured by computed tomography (CT) volumetry was 166% of the recipient's chest cavity volume. Right pneumonectomy followed by implantation was performed under cardiopulmonary bypass (CPB). The pulmonary arterial pressure was significantly decreased to 31/12 mm Hg immediately after transplantation, and the first PaO2 /FiO2 in the intensive-care unit (ICU) was 422 mm Hg. Lung perfusion scintigraphy showed 97.5% perfusion to the right implanted lung 3 months after transplantation. Chest CT showed a mass rapidly growing in the native left upper lobe 6 months after transplantation, which was diagnosed as posttransplant lymphoproliferative disorder (PTLD) by a CT-guided biopsy. After immunosuppressant reduction and six courses of chemotherapy with rituximab, he underwent native left upper lobectomy for salvage lung resection 13 months after transplantation. Seven months after lobectomy, he has returned to normal school life without any sign of tumor recurrence.

[Thoracoscopic Left Upper Division Segmentectomy for Multiple Ground-glass Nodules Using Preoperative Virtual-assisted Lung Mapping].

Associated with an increase of small-sized lung cancer or metachronous second primary lung cancer, we have more opportunities to perform sublobar resection. Difficulties of identifying tumor location and appropriate surgical margin for small-sized ground-glass opacity (GGO) dominant lesions in thoracoscopic surgery is the big issue of sublobar resection. Virtual-assisted lung mapping (VAL-MAP) that makes markings on the lung surface through some peripheral bronchi by bronchoscopically projects intrapulmonary anatomy on the lung surface and literally draw a map. We report a case of thoracoscopic left upper division segmentectomy for multiple ground-glass nodules (GGNs) using preoperative VAL-MAP. A 65-year-old women who had undergone right upper lobectomy for primary lung cancer, and had multiple GGNs in the bilateral lungs was followed up as an outpatient. Eleven years after initial pulmonary resection, 2 lesions in the left upper division became bigger, and we decided to perform surgery for 4 GGNs in the left upper division including these 2 lesions. We preoperatively made bronchoscopic dye markings through B1+2c, B3a and B4a for in the left upper lobe. The 3 markings were intraoperatively identified. We decided the resection line based on the markings and performed thoracoscopic left upper division segmentectomy. The pathological diagnosis was minimally invasive adenocarcinoma, adenocarcinoma in situ and pneumonitis. Surgical margins were negative. VAL-MAP will assume an important role as an intraoperative navigation system for sublobar resection.

The impact of emphysema on surgical outcomes of early-stage lung cancer: a retrospective study.

BACKGROUND: The presence of emphysema on computed tomography (CT) is associated with an increased frequency of lung cancer, but the postoperative outcomes of patients with pulmonary emphysema are not well known. The objective of this study was to investigate the association between the extent of emphysema and long-term outcomes, as well as mortality and postoperative complications, in early-stage lung cancer patients after pulmonary resection. METHODS: The clinical records of 566 consecutive lung cancer patients who underwent pulmonary resection in our department were retrospectively reviewed. Among these, the data sets of 364 pathological stage I patients were available. The associations between the extent of lung emphysema and long-term outcomes and postoperative complications were investigated. Emphysema was assessed on the basis of semiquantitative CT. Surgery-related complications of Grade ≥ II according to the Clavien-Dindo classification were included in this study. RESULTS: Emphysema was present in 63 patients. The overall survival and relapse-free survival of the non-emphysema and emphysema groups at 5 years were 89.0 and 61.3% (P < 0.001), respectively, and 81.0 and 51.7%, respectively (P < 0.001). On multivariate analysis, significant prognostic factors were emphysema, higher smoking index, and higher histologic grade (p < 0.05). Significant risk factors for poor recurrence-free survival were emphysema, higher smoking index, higher histologic grade, and presence of pleural invasion (P < 0.05). Regarding Grade ≥ II postoperative complications, pneumonia and supraventricular tachycardia were more frequent in the emphysema group than in the non-emphysema group (P = 0.003 and P = 0.021, respectively). CONCLUSION: The presence of emphysema affects the long-term outcomes and the development of postoperative complications in early-stage lung cancer patients.

Early and mid-term outcomes of simultaneous thoracic endovascular stent grafting and combined resection of thoracic malignancies and the aortic wall.

OBJECTIVES: To aim of this study was to clarify the safety of simultaneous thoracic aortic endografting and combined resection of the aortic wall and thoracic malignancy in a one-stage procedure over the early and mid-term periods. METHODS: From March 2013 to December 2017, 6 patients underwent aortic endografting followed by one-stage en bloc resection of the tumor and aortic wall. Thoracic surgeons and cardiovascular surgeons discussed predicted tumor invasion range and resection site, stent placement position, stent length and size, and the surgical procedure, taking into account the safe margin. RESULTS: The proximal site of aortic endografting was the: aortic arch in 2 cases (subclavian artery (SCA) occlusion in one, and SCA fenestration in one); distal arch just beneath the SCA in 2; descending aorta in 2. Pulmonary resection involved lobectomy in 2 patients, pneumonectomy in 2, and completion pneumonectomy in 1. Aortic resection was limited to the adventitia in 2 cases, extended to the media in 3, and extended to the intima in 1. An endograft-related complication, external iliac artery intimal damage requiring vessel repair, was observed in one case. No complications associated with aortic resection were observed. Two postoperative complications of atrial fibrillation and chylothorax developed. There were no surgery-related deaths. During follow-up, no late endograft-related complications such as migration or endoleaks occurred. CONCLUSIONS: Early and mid-term outcomes of stent graft-related complications are acceptable. Simultaneous thoracic aortic endografting and combined resection of the aortic wall and thoracic malignancies are feasible in one stage on the same day.