Clinical utility of psoas muscle volume in assessment of sarcopenia in patients with early-stage non-small cell lung cancer.

PURPOSE: Sarcopenia influences postoperative outcomes of patients with non-small cell lung cancer (NSCLC). Imaging tools for evaluating and diagnosing sarcopenia have developed, and a novel method of psoas volume index (PVI) obtained by measuring bilateral psoas major muscle volume has been reported. However, the relationship between sarcopenia based on PVI and clinical outcomes has not been fully investigated for patients with early-stage NSCLC. This study aimed to clarify the utility of PVI values in assessing the relationshipe between sarcopenia and clinical outcomes. METHODS: This study included 645 patients with stage I-II NSCLC who underwent curative lung resection between 2012 and 2017. Bilateral psoas major muscle volumes were calculated semi-automatically using a three-dimensional workstation. The cutoff value of PVI for defining sarcopenia was < 60.5 cm3/m3 for men and < 43.6 cm3/m3 for women. RESULTS: The avrage time to obtaine PVI was only 25 s with the 3D system, and interobserver agreements for evauating sarcopenia on PVI was 1. A total of 159 patients (24.7%) were preoperatively diagnosed with sarcopenia. On multivariate analysis, sarcopenia was an independent prognostic factor for overall survival (OS, p < 0.001), recurrence-free survival (RFS, p < 0.001), and lung cancer-specific survival (LCS, p < 0.001). The 5-year OS, RFS, and LCS were significantly worse in sarcopenic patients than non-sarcopenic patients (88.8 vs. 72.4%, p < 0.001; 80.1 vs. 65.0%, p < 0.001; 92.4 vs. 78.9%, p < 0.001, respectively). CONCLUSION: Sarcopenia diagnosed using PVI is an independent prognostic predictor of OS, RFS, and LCS in early-stage NSCLC.

Prognostic impact of artificial intelligence-based volumetric quantification of the solid part of the tumor in clinical stage 0-I adenocarcinoma.

INTRODUCTION: The size of the solid part of a tumor, as measured using thin-section computed tomography, can help predict disease prognosis in patients with early-stage lung cancer. Although three-dimensional volumetric analysis may be more useful than two-dimensional evaluation, measuring the solid part of some lesions is difficult using this methods. We developed an artificial intelligence-based analysis software that can distinguish the solid and non-solid parts (ground-grass opacity). This software calculates the solid part volume in a totally automated and reproducible manner. The predictive performance of the artificial intelligence software was evaluated in terms of survival or recurrence-free survival. METHODS: We analyzed the high-resolution computed tomography images of the primary lesion in 772 consecutive patients with clinical stage 0-I adenocarcinoma. We performed automated measurement of the solid part volume using an artificial intelligence-based algorithm in collaboration with FUJIFILM Corporation. The solid part size, the solid part volume based on traditional three-dimensional volumetric analysis, and the solid part volume based on artificial intelligence were compared. RESULTS: Higher areas under the curve related to the solid part volume were provided by the artificial intelligence-based method (0.752) than by the solid part size (0.722) and traditional three-dimensional volumetric analysis-based method (0.723). Multivariate analysis demonstrated that the solid part volume based on artificial intelligence was independently correlated with overall survival (P = 0.019) and recurrence-free survival (P < 0.001). CONCLUSION: The solid part volume measured by artificial intelligence was superior to conventional methods in predicting the prognosis of clinical stage 0-I adenocarcinoma.

Effect of photodynamic therapy (PDT) on a rat model of bleomycin-induced interstitial pneumonia.

BACKGROUND: Even if lung cancer is detected at an early stage, surgery may be difficult in patients with severe comorbidities, like interstitial pneumonia (IP). Radiation therapy cannot be performed due to the high risk of acute IP exacerbation. Therefore, an effective alternative, such as photodynamic therapy (PDT), is required. To prove that acute exacerbation is not induced after PDT in peripheral lung cancer, we investigated the effects of PDT on IP rat models. METHODS: Bleomycin (BLM) was administered intratracheally. Seven days after administration, left thoracotomy was performed. Talaporfin sodium was injected, and diode laser irradiation (664 nm, 150mW, 100J/cm2) was performed. Seven days after PDT, the whole blood and left lungs were collected. A total of 23 rats, comprising BLM + PDT (n = 4), BLM + non-PDT (n = 10), non-BLM + PDT (n = 2), non-BLM + non-PDT (n = 5), and two rats that died immediately after PDT were observed. Serum levels of Krebs von den Lungen-6, surfactant protein-D, lactate dehydrogenase, and serum C-reactive protein were measured. Fibrosis and macrophage scorings, and the ​​collagen fibers percentage were examined by staining with hematoxylin and eosin, Elastica van Gieson, anti-α smooth muscle antibody, and anti-CD68 antibodies. RESULTS: There was no remarkable difference in the values of each marker in fibrosis and macrophage scores with or without PDT. In case of death, fibrosis was mild, and PDT was not affected. CONCLUSIONS: In IP rat models, PDT did not induce lung fibrosis or acute exacerbation.

Artificial intelligence analysis of three-dimensional imaging data derives factors associated with postoperative recurrence in patients with radiologically solid-predominant small-sized lung cancers.

OBJECTIVES: Indications of limited resection, such as segmentectomy, have recently been reported for patients with solid-predominant lung cancers ≤2 cm. This study aims to identify unfavourable prognostic factors using three-dimensional imaging analysis with artificial intelligence (AI) technology. METHODS: A total of 157 patients who had clinical N0 non-small cell lung cancer with a radiological size ≤2 cm, and a consolidation tumour ratio > 0.5, who underwent anatomical lung resection between 2011 and 2017 were enrolled. To evaluate the three-dimensional structure, the ground-glass nodule/Solid Automatic Identification AI software Beta Version (AI software; Fujifilm Corporation, Japan) was used. RESULTS: Maximum standardized uptake value (SUVmax) and solid-part volume measured by AI software (AI-SV) showed significant differences between the 139 patients with adenocarcinoma and the 18 patients with non-adenocarcinoma. Among the adenocarcinoma patients, 42 patients (30.2%) were found to be pathological upstaging. Multivariable analysis demonstrated that high SUVmax, high carcinoembryonic antigen level and high AI-SV were significant prognostic factors for recurrence-free survival (RFS; P < 0.05). The 5-year RFS was compared between patients with tumours showing high SUVmax and those showing low SUVmax (67.7% vs 95.4%, respectively, P < 0.001). The 5-year RFS was 91.0% in patients with small AI-SV and 68.1% in those with high AI-SV (P = 0.001). CONCLUSIONS: High AI-SV, high SUVmax and abnormal carcinoembryonic antigen level were unfavourable prognostic factors of patients with solid-predominant lung adenocarcinoma with a radiological size ≤2 cm. Our results suggest that lobectomy should be preferred to segmentectomy for patients with these prognostic factors.

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.

Comparative analysis of the results of video-assisted thoracic surgery lobectomy simulation using the three-dimensional-printed Biotexture wet-lung model and surgeons' experience.

OBJECTIVES: We performed a comparative analysis of the performance of video-assisted thoracic surgery (VATS) lobectomy simulation using three-dimensional-printed Biotexture lung models by surgeons classified according to their level of expertise. The aim of this study was to investigate the association between surgeons' experience and time to complete the VATS lobectomy simulation. METHODS: Participants were divided into 3 groups: group A included those who had no experience of actual VATS lobectomy (n = 11), group B included those who had performed 5-10 VATS lobectomies (n = 12) and group C included those who had performed >100 VATS lobectomies (n = 6). Their performances were assessed based on total procedure time, duration to the exposure of the vessels, ligation of the arteries and stapling of the fissures. After the simulation, a questionnaire survey was performed. RESULTS: The median total procedure time was significantly shorter in the group of surgeons with more experience (A vs B, P < 0.001; B vs C, P = 0.034; A vs C, P < 0.001). Regarding 'the exposure of all the vessels to be resected' and 'ligation of the arteries', group B completed these steps in less time than group A (P = 0.024 and P = 0.012, respectively). In the questionnaire, all groups answered that this simulation was useful for novices to improve their skills. CONCLUSIONS: Although time to complete the VATS lobectomy simulation is only a part of evaluation points for real skills, this model can facilitate basic skill acquisitions for novices.

Prognostic impact of solid-part tumour volume doubling time in patients with radiological part-solid or solid lung cancer.

OBJECTIVES: The measurement of part-solid and whole tumour sizes in patients with non-small-cell lung cancer (NSCLC) using computed tomography (CT) has been widely accepted for assessing clinical outcomes. Although the volume doubling time (VDT) of a tumour is useful for distinguishing high-risk nodules from low-risk ones, it remains to be clarified whether separate calculation of whole-tumour VDT and solid-part tumour VDT (SVDT) greatly affects the survival rate of patients with radiologically node-negative part-solid or solid NSCLC. METHODS: The study included 258 patients with NSCLC who had radiologically node-negative, part-solid or solid tumours and who had at least 2 preoperative CT scans taken more than 30 days apart followed by radical lobectomy and systemic lymph node dissection between January 2012 and December 2015. Univariable and multivariable analyses of recurrence-free survival were performed using the Cox proportional hazards regression model. RESULTS: The mean whole-tumour VDT and SVDT were 375 and 458 days, respectively. Multivariable analyses demonstrated that whole-tumour VDT (P = 0.003), SVDT (P < 0.001), solid-part tumour size, whole-tumour size and comorbidities significantly affected the recurrence-free survival. Using the receiver operating characteristic curve, the cut-off value of the SVDT for recurrence was 215 days, and the 5-year recurrence-free survival rates for patients with SVDT >215 days and those with SVDT <215 days were 85.7% and 43.0%, respectively (P < 0.001). CONCLUSION: The calculation of SVDT in patients with node-negative, part-solid or solid NSCLC is highly useful for predicting postoperative survival outcomes.

Correction to: Successful adjustment for self-expanding metallic stent migration using a flexible bronchoscope with two biopsy forceps technique.

In the original publication of the article, the corresponding author email address was published wrongly.

Assessment of emphysema severity as measured on three-dimensional computed tomography images for predicting respiratory complications after lung surgery.

OBJECTIVES: Emphysema is one of the main causes of respiratory complications in patients operated on for lung cancer. We have used three-dimensional computed tomography (3D CT) for surgical simulations, as well as for depicting emphysematous areas as low attenuation areas (LAAs) and visual scores based on the Goddard classification (Goddard score), which is a visual scale of the area of vascular disruption and LAA for each lung field. This study aimed to investigate the effectiveness of the 3D CT function for assessing emphysema severity and its association with respiratory complications. METHODS: The study included 504 lung cancer patients who had preoperative 3D CT from October 2010 to March 2015. Goddard score and LAA% (LAA/total lung volume) were measured using 3D CT data. The relationship between respiratory complications and independent variables was investigated. RESULTS: Postoperative respiratory complications were observed in 69 (13.6%) patients. The receiver operating characteristic curves for respiratory complications determined using the Goddard score and LAA% dichotomized at each cut-off level (1 and 0.7%, respectively) showed that the events were observed in 32% of the patients with a Goddard score ≥1 and in 25% of the patients with an LAA% ≥0.7. On multivariable analyses, the Goddard score was significantly correlated with postoperative respiratory complications (P < 0.001). CONCLUSIONS: Preoperative measurement of the Goddard score and LAA% using 3D CT in patients with lung cancer, particularly with the coexistence of emphysema, was beneficial for predicting postoperative respiratory complications.

Successful adjustment for self-expanding metallic stent migration using a flexible bronchoscope with two biopsy forceps technique.

Although tracheobronchial stents are widely used for tracheal obstruction due to malignant or benign stenosis, stent migration has been reported as a major postoperative complication. A self-expandable metallic stent (SEMS) is more easily introduced compared with silicone stents. However, it is also difficult to remove or replace without complications. We report a new technique for successful SEMS adjustment using a flexible bronchoscope with two biopsy forceps.

Repression of Smad3 by Stat3 and c-Ski/SnoN induces gefitinib resistance in lung adenocarcinoma.

Cancer-associated inflammation develops resistance to the epidermal growth-factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in non-small cell lung cancers (NSCLCs) harboring oncogenic EGFR mutations. Stat3-mediated interleukin (IL)-6 signaling and Smad-mediated transforming growth factor-ß (TGF-ß) signaling pathways play crucial regulatory roles in cancer-associated inflammation. However, mechanisms how these pathways regulate sensitivity and resistance to EGFR-TKI in NSCLCs remain largely undetermined. Here we show that signal transducer and activator of transcription (Stat)3 represses Smad3 in synergy with the potent negative regulators of TGF-ß signaling, c-Ski and SnoN, whereby renders gefitinib-sensitive HCC827 cells resistant. We found that IL-6 signaling via phosphorylated Stat3 induced gefitinib resistance as repressing transcription of Smad3, whereas TGF-ß enhanced gefitinib sensitivity as activating transcription of Smad3 in HCC827 cells with gefitinib-sensitizing EGFR mutation. Promoter analyses showed that Stat3 synergized with c-Ski/SnoN to repress Smad2/3/4-induced transcription of the Smad3 gene. Smad3 was found to be an apoptosis inducer, which upregulated pro-apoptotic genes such as caspase-3 and downregulated anti-apoptotic genes such as Bcl-2. Our results suggest that derepression of Smad3 can be a therapeutic strategy to prevent gefitinib-resistance in NSCLCs with gefitinib-sensitizing EGFR mutation.

High-quality 3-dimensional image simulation for pulmonary lobectomy and segmentectomy: results of preoperative assessment of pulmonary vessels and short-term surgical outcomes in consecutive patients undergoing video-assisted thoracic surgery†.

OBJECTIVES: The aim of this study was to evaluate the effectiveness of 3-dimensional computed tomography (3D-CT) software in short-term surgical outcomes and the assessment of variations of pulmonary vessel branching patterns on performing video-assisted thoracic surgery (VATS). METHODS: The study included 179 consecutive patients who had undergone VATS anatomical lung resection, of which 172 were lobectomies (96%) and 7 were segmentectomies (4%), from May 2011 through January 2013. There were 124 patients (69%) in whom 3D-CT was performed and 55 patients (31%) who had not undergone 3D-CT. Observed actual pulmonary vessel branching patterns by intraoperative findings or footage were compared with the 3D image findings. Various surgical outcomes, including the occurrence of postoperative complications, in this study defined as those of Grade 2 or above under the Clavien-Dindo classification system, and total operative time, were retrieved from available clinical records. RESULTS: Among the 124 patients with preoperative 3D imaging, there were 5 (4%) conversions from VATS to thoracotomy. The incidence rate of patients with postoperative complications was 8% (n = 10), and there were no 30-day or 90-day mortalities. Pulmonary artery (PA) branches were precisely identified for 97.8% (309 of 316) of branches on 3D images, and the sizes of the seven undetected branches (five in the right upper lobe, two in the left upper lobe) ranged from 1 to 2 mm. The 3D images accurately revealed 15 cases (12%) of anomalous or unusual PA branches and 5 cases (4%) of variant pulmonary veins. Multivariate logistic regression analysis of the association with postoperative complications and operative time in 165 lung cancer patients demonstrated that male gender was the only statistically significant independent predictor of complications (risk ratio: 5.432, P = 0.013), and patients without 3D imaging tended to have operative complications (risk ratio: 2.852, P = 0.074), whereas conducting the 3D-CT (risk ratio: 2.282, P = 0.021) as well as intraoperative bleeding amount (risk ratio: 1.005, P = 0.005) had significant association with operative time. CONCLUSIONS: High-quality 3D-CT images clearly revealed the anatomies of pulmonary vessels, which could play important roles in safe and efficient VATS anatomical resection.

The thoracodorsal vascular tree-based combined fascial flaps.

In this study, combined fascial flaps pedicled on the thoracodorsal artery and vein were raised and used for thin coverage of dorsal surfaces of the fingers and the dorsum of hand and foot with favorable results. The combined fascial flaps consist of the serratus anterior fascia and the axillary fascia at the entrance of the latissimus dorsi. These flaps were used for reconstruction of the hand, fingers, or foot in nine patients. Reconstruction was performed for burn or burn scar contracture, after resection of malignant tumors, posttraumatic skin defects, and chronic regional pain syndrome. The sites of reconstruction were dorsal surfaces of fingers, dorsum of hand, wrist and palm, forearm, lower leg, and foot. The flaps were used in various configurations including two independent fascial flaps, two-lobed fascial flap with separate feeding vessels, and composite fascial and thoracodorsal artery perforator flap. The fascial and skin flaps survived in all nine patients, with favorable results both functionally and esthetically. Good coverage of soft tissue defects and good recovery of range of motion in resurfaced joints were achieved. There were no complications. The scars at the sites of harvest were not noticeable. The advantage of this method is that not only a single flap but flaps of a variety of configurations can be harvested for different purposes. The thoracodorsal vascular tree-based combined fascial flaps are useful for the reconstruction of soft tissue defects in the extremities.

Muscle sparing-2 transverse rectus abdominis musculocutaneous flap for breast reconstruction: a comparison with deep inferior epigastric perforator flap.

Breast reconstruction using free transverse rectus abdominis musculocutaneous (TRAM) flap can be divided into 4 muscle-sparing (MS) types: conventional TRAM flap containing full width muscle as MS-0, while deep inferior epigastric perforator (DIEP) flap containing absolutely no muscle as MS-3. We include only the muscle portion between the medial row and lateral row perforator vessels in TRAM flap, which is designated as MS-2. Between October 1999 and April 2006, the same surgeon performed 82 breast constructions using MS-2 free TRAM flaps in 79 patients. All the flaps survived. Postoperative complications included partial fat necrosis in 8 cases, all corresponding to zone IV or zone II. Bulging of donor site occurred in 5 patients, 4 of whom were obese and 1 had bilateral flap harvest. Compared with our own reconstructions using DIEP flap (30 cases), there were no significant differences in operative time and blood loss between the two techniques. In conclusion, MS-2 free TRAM flap is a useful technique for breast construction considering the easy surgical techniques, length of the vascular pedicle that can be harvested, and the degree of freedom of the flap.

Kimura disease: diagnostic imaging findings and surgical treatment.

We have encountered 11 cases of Kimura disease, comprising 10 males and 1 female. The ages at presentation ranged from 16 to 48 years, with a mean of 31.5 years. The sites of the subcutaneous masses were bilateral posterior auricular regions in two cases, frontal region in two cases, temporal region in two cases, head region in one case, parotid region in two cases, parotid and temporal regions in one case, and left earlobe in one case. The interval from onset to surgery ranged from 1 to 10 years, with a mean of 4.7 years. For diagnostic imaging, a combination of magnetic resonance imaging (MRI) and ultrasonography had a high diagnostic value. MRI depicted abnormalities at sites in contact with bone, such as posterior auricular regions, and sites with abundant soft tissue, such as parotid and cheek regions. Diffuse atrophy of subcutaneous fat was observed at the sites of the masses. On ultrasonography, the interior of lymph nodes was homogeneous and hyperechoic, whereas the periphery was hyperechoic, and blood vessels entering lymph nodes were clearly depicted. Surgery was performed in all cases. Postoperative adjuvant radiotherapy was conducted in one patient and radiotherapy and steroid therapy in one other patient. There were two relapses, and both were excised by repeated surgery. Surgical excision of the subcutaneous mass in Kimura disease has the advantages that the treatment period is short and precise histopathologic diagnosis can be obtained.