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BackgroundFew studies have assessed the comprehensive skeletal muscle depletion associated with loss of muscle quantity (sarcopenia) and reduced muscle quality in cancer patients. This study aimed to clarify the impact of skeletal muscle depletion on outcomes after non-small cell lung cancer surgery.MethodsData for 341 patients with pathologic stages 1 to 3A non-small cell lung cancer who underwent lobectomy and mediastinal lymph node dissection from 2009 to 2013 were retrospectively reviewed. The integrative pectoralis muscle index (IPMI) was assessed by multiplying the normalized pectoralis muscle area (area/body mass index) and mean radiodensity on chest images. Postoperative outcomes were compared among sex-specific quartiles of IPMI. The trend of continuous and categorical variables was analyzed using the Jonckheere–Terpstra test and the Cochrane–Armitage test, respectively.ResultsRespiratory strength declined with decreasing quartiles of IPMI (P < 0.001). The risk of major complications escalated with the decrease of IPMI among four quartiles (7.1 %, 16.7 %, 18.4 %, and 22.4 %; P = 0.008). The hospital stay was prolonged for patients with reduced IPMI (P = 0.001). Patients in the lowest and highest quartiles had the worst and best 5-year overall survival, respectively, compared with those in the two intermediate quartiles of IPMI (67.0 %, 87.9 %, and 81.2 %, respectively; P=0.001). Multivariate analysis identified the lowest quartile of IPMI as an independent poor prognostic factor (hazard ratio, 1.88; 95 % confidence interval, 1.11–3.19; P = 0.020).ConclusionComprehensive skeletal muscle profiling, including morphometric mass and componential density on chest imaging, has the potential to refine risk stratification and prognostication in non-small cell lung cancer.

The importance of neoantigens for cancer immunity is now well‐acknowledged. However, there are diverse strategies for predicting and prioritizing candidate neoantigens, and thus reported neoantigen loads vary a great deal. To clarify this issue, we compared the numbers of neoantigen candidates predicted by four currently utilized strategies. Whole‐exome sequencing and RNA sequencing (RNA‐Seq) of four non‐small‐cell lung cancer patients was carried out. We identified 361 somatic missense mutations from which 224 candidate neoantigens were predicted using MHC class I binding affinity prediction software (strategy I). Of these, 207 exceeded the set threshold of gene expression (fragments per kilobase of transcript per million fragments mapped ≥1), resulting in 124 candidate neoantigens (strategy II). To verify mutant mRNA expression, sequencing of amplicons from tumor cDNA including each mutation was undertaken; 204 of the 207 mutations were successfully sequenced, yielding 121 mutant mRNA sequences, resulting in 75 candidate neoantigens (strategy III). Sequence information was extracted from RNA‐Seq to confirm the presence of mutated mRNA. Variant allele frequencies ≥0.04 in RNA‐Seq were found for 117 of the 207 mutations and regarded as expressed in the tumor, and finally, 72 candidate neoantigens were predicted (strategy IV). Without additional amplicon sequencing of cDNA, strategy IV was comparable to strategy III. We therefore propose strategy IV as a practical and appropriate strategy to predict candidate neoantigens fully utilizing currently available information. It is of note that different neoantigen loads were deduced from the same tumors depending on the strategies applied. There are diverse strategies for predicting and prioritizing candidate neoantigens, and thus neoantigen loads reported in the literature vary a great deal. In this study, neoantigen candidates were predicted by four currently utilized strategies. We found that numbers of neoantigen candidates differed substantially depending on which strategy was used, and that integration of both expression data and sequence data from RNA‐Seq with whole‐exome sequencing data enabled us to predict and prioritize candidate neoantigens efficiently and appropriately.

A 62-year-old man presented with back pain, lower leg swelling, and fever and was referred to our hospital. Blood cultures identified as the causative agent of bacteremia associated with pyogenic spondylitis and cellulitis. CT revealed a tumor in the upper anterior mediastinum, and blood tests showed low gamma globulin levels, raising the suspicion of Good's syndrome. Infection control was prioritized, and the patient received antibiotics for four weeks. After blood cultures returned negative, preoperative gamma globulin was administered to mitigate infection risk, and a total thymectomy was planned. A bilateral three-port thoracoscopic total thymectomy was performed, and the patient was observed as an outpatient without any postoperative infection recurrence. We present a case of Good's syndrome with a high infection risk, successfully managed with a minimally invasive bilateral three-port thoracoscopic total thymectomy and effective perioperative infection control.

Introduction With the global trend of aging populations, the number of nonagenarians diagnosed with malignancies, including lung cancer, is increasing. Despite advancements in minimally invasive surgical techniques, lung resection for nonagenarians remains rare due to concerns regarding comorbidities and surgical risks. This study evaluates the surgical outcomes of lung resection in nonagenarians and introduces a holistic assessment approach to optimize patient care. Methods A retrospective review of surgical records from January 2011 to December 2022 identified seven nonagenarians who underwent lung resection under 3-port video-assisted thoracoscopic surgery (VATS). Patient characteristics, surgical details, and postoperative outcomes were analyzed. To holistically evaluate each patient, multifaceted surgical tolerance and prognostic factors were summarized and visualized in a radar plot. Results The study cohort consisted of four males and three females aged 90 to 96 years. Wedge resection was performed in six patients, and one patient underwent lobectomy. Mediastinal lymph node dissection was not performed. The median duration of chest tube insertion was two days, and 86% of patients were discharged within one week. Postoperative complications were minimal, with one case of delirium and no occurrences of pneumonia. All patients were discharged in stable condition without deterioration of their activities of daily living. The median overall survival was 4.1 years. One patient succumbed to lung cancer progression, while the remaining patients exhibited favorable long-term survival without recurrence, including one patient whose lung tumor was a metastasis from colorectal cancer. As depicted in the radar plots, all patients had at least one risk factor other than their age. Conclusion Lung resection under a minimally invasive approach is feasible for carefully selected nonagenarians, yielding favorable short- and long-term outcomes. Because super-elderlies likely harbor multiple comorbidities, a holistic assessment of each patient is important for personalized patient care.

Objective Conventional virtual-assisted lung mapping (VAL-MAP), also termed multi-spot preoperative bronchoscopic lung marking, necessitates post-mapping computed tomography (CT) to confirm the locations of dye markings. We hypothesized that electromagnetic navigation bronchoscopy (ENB) simplifies VAL-MAP by omitting post-mapping CT. Methods Under general anesthesia, real-time navigation bronchoscopy was conducted using ENB to reach a site as close to the planned location as possible, and indigo carmine was injected. Initially, surgery was then performed (no-adjustment group; 5 lesions of 3 patients). Later, on-site adjustment was added before surgery (adjustment group; 4 lesions of 4 patients), in which the locational information of ENB was transferred to a radiology workstation to construct an adjusted three-dimensional image. The accuracy of each predicted marking location was graded based on intraoperative observation. After the analysis, 19 patients with 21 lesions underwent ENB VAL-MAP with on-site adjustment (practice set) to evaluate the surgical outcomes. Results The accuracy of the predicted marking location was significantly higher in the adjustment than no-adjustment group (4.7 ± 0.7 vs. 3.4 ± 1.2, respectively; P  = 0.01), especially among the markings for which the bronchoscope did not reach the planned location (4.5 ± 0.8 vs. 2.6 ± 0.5, respectively; P  = 0.004). In the practice set, the lung map quality was satisfactory and the resection outcome was successful with a sufficient macroscopic resection margin in 19/21 lesions (90.5%). Conclusion The ENB VAL-MAP quality was improved by adding on-site adjustment, achieving clinical outcomes similar to conventional VAL-MAP. The logistic challenge of post-mapping CT in conventional VAL-MAP can be partially overcome by ENB VAL-MAP with on-site adjustment.

Background Bronchial necrosis is a rare but fatal complication after radiation therapy. Because of the anatomical complexity and rarity of this condition, determining the most appropriate management for individual patients is extremely challenging. Lung autotransplantation is a surgical technique that has been applied to hilar neoplastic lesions to preserve pulmonary function and avoid pneumonectomy. We herein report a case of bronchial necrosis secondary to radiotherapy that was treated with lung autotransplantation. Case presentation A 46-year-old man developed broad necrosis and infection of the right bronchus secondary to previous stereotactic body-radiation therapy. This treatment was supplied close to a right hilar metastatic pulmonary tumor derived from a mediastinal malignant germ cell tumor that had been surgically resected with the left phrenic nerve. The bronchial necrosis accompanied by infection with Aspergillus fumigatus was progressive despite antibiotics and repetitive bronchoscopic debridement. Because of the patient’s critical condition and limited pulmonary function, right lung autotransplantation with preservation of the right basal segment was selected. An omental flap was placed around the bronchial anastomosis to prevent later complications. The postoperative course involved multiple complications including contralateral pneumonia and delayed wound healing at the bronchial anastomosis with resultant stenosis, the latter of which was overcome by placement of a silicone stent. The patient was discharged 5 months postoperatively. Three months after discharge, however, the patient developed hemoptysis and died of bronchopulmonary arterial fistula formation. Conclusions We experienced an extremely challenging case of bronchial necrosis secondary to radiotherapy. The condition was managed with lung autotransplantation and omental wrapping; however, the treatment success was temporary and the patient eventually died of bronchopulmonary arterial fistula formation. This technique seems to be a feasible option for locally advanced refractory bronchial necrosis, although later complications can still be fatal.

The treatment of multi-organ synchronous neoplasms requires a customized strategy for each case. Here, we present our treatment strategy for synchronous double neoplasms involving thymoma and esophageal cancer, which is a rare occurrence in clinical practice. A 68-year-old man was diagnosed with thymoma and advanced esophageal cancer in the middle thoracic esophagus. Following neoadjuvant chemotherapy for esophageal cancer, a concurrent resection of both lesions was performed using minimally invasive unilateral video-assisted thoracoscopic surgery and laparoscopic surgery with gastric conduit reconstruction via the posterior mediastinal route. The patient was discharged on the 14th postoperative day without any adverse events. Minimally invasive, video-assisted unilateral simultaneous surgery for thymoma and esophageal cancer represents a viable therapeutic approach, offering both curative potential and decreased invasiveness. Furthermore, reconstructing the gastric conduit via the posterior mediastinal route was deemed appropriate, as it may help minimize the risk of invasion of the gastric conduit and radiation exposure in the event of thymoma disease progression. Additionally, we propose a treatment strategy flow for synchronous neoplasms located in adjacent multi-organs. This strategy can be applied to various tumor types and may benefit other complex cases.

BackgroundNot all non-small cell lung cancer (NSCLC) patients possess drug-targetable driver mutations, and response rates to immune checkpoint blockade therapies also remain unsatisfactory. Therefore, more effective treatments are still needed. Here, we report the results of a phase 2 clinical trial of adoptive cell therapy using zoledronate-expanded autologous Vγ9Vδ2 T-cells for treatment-refractory NSCLC.MethodsNSCLC patients who had undergone at least two regimens of standard chemotherapy for unresectable disease or had had at least one treatment including chemotherapy or radiation for recurrent disease after surgery were enrolled in this open-label, single-arm, multicenter, phase 2 study. After preliminary testing of Vγ9Vδ2 T-cell proliferation, autologous peripheral blood mononuclear cells were cultured with zoledronate and IL-2 to expand the Vγ9Vδ2 T-cells. Cultured cells (>1×109) were intravenously administered every 2 weeks for six injections. The primary endpoint of this study was progression-free survival (PFS), and secondary endpoints included overall survival (OS), best objective response rate (ORR), disease control rate (DCR), safety and immunomonitoring. Clinical efficacy was defined as median PFS significantly >4 months.ResultsTwenty-five patients (20 adenocarcinoma, 4 squamous cell carcinoma and 1 large cell carcinoma) were enrolled. Autologous Vγ9Vδ2 T-cell therapy was administered to all 25 patients, of which 16 completed the foreseen course of 6 injections of cultured cells. Median PFS was 95.0 days (95% CI 73.0 to 132.0 days); median OS was 418.0 days (179.0–479.0 days), and best overall responses were 1 partial response, 16 stable disease (SD) and 8 progressive disease. ORR and DCR were 4.0% (0.1%–20.4%) and 68.0% (46.5%–85.1%), respectively. Severe adverse events developed in nine patients, mostly associated with disease progression. In one patient, pneumonitis and inflammatory responses resulted from Vγ9Vδ2 T-cell infusions, together with the disappearance of a massive tumor.ConclusionsAlthough autologous Vγ9Vδ2 T-cell therapy was well tolerated and may have an acceptable DCR, this trial did not meet its primary efficacy endpoint.Trial registration numberUMIN000006128

ABSTRACT Introduction: Survival information for stereotactic body radiotherapy (SBRT) and surgery for stage I non-small cell lung cancer (NSCLC) was examined. Methods: Stage I NSCLC patients who underwent surgery or SBRT between 2012 and 2016 were retrospectively enrolled in this single-institution study. Using the Kaplan--Meier method and Cox regression model, overall survival (OS) was estimated and compared. Results: Among 538 enrolled patients, compared to the surgery group (443), the SBRT group (95) had more complications (P = 0.01), worse performance status (P = 0.001), and were older (P < 0.001). Three-year OS was 70.5% post SBRT and 90.1% postsurgery. The 3-year cancer-specific survival (CSS) and disease-free survival (DFS) post SBRT and postsurgery were 92.7% vs. 92.3% and 61.1% vs 79.3%, respectively. Three-year locoregional and distant control rates post SBRT and postsurgery were 85.6% vs. 90.1% and 82.5% vs. 86.4%, respectively. Multivariate analysis using the Cox model, including age, T-stage, CCI, and C/T ratio and treatment, showed the surgery group's OS to be significantly superior to that of the SBRT group (HR of SBRT per surgery: 1.90, 95%CI: 1.12-3.21, P = 0.017). No significant differences were observed in rates of adverse events. Conclusion: Although OS was better in the surgery group, no differences in CSS existed. This analysis suggests the need for future studies that compare specific radical surgeries and SBRT in a prospective and randomized setting.