Tumor invasion in lung adenocarcinoma is defined as infiltration of stroma, blood vessels, or pleura. Based on observation of tumor spread through air spaces (STAS), we considered whether this could ...represent new patterns of invasion and investigated whether it correlated with locoregional versus distant recurrence according to limited resection versus lobectomy.
We reviewed resected small (less than or equal to 2 cm) stage I lung adenocarcinomas (n = 411; 1995–2006). Tumor STAS was defined as tumor cells—micropapillary structures, solid nests, or single cells—spreading within air spaces in the lung parenchyma beyond the edge of the main tumor. Competing risks methods were used to estimate risk of disease recurrence and its associations with clinicopathological risk factors.
STAS was observed in 155 cases (38%). In the limited resection group (n = 120), the risk of any recurrence was significantly higher in patients with STAS-positive tumors than that of patients with STAS-negative tumors (5-year cumulative incidence of recurrence, 42.6% versus 10.9%; P < 0.001); the presence of STAS correlated with higher risk of distant (P = 0.035) and locoregional recurrence (P = 0.001). However, in the lobectomy group (n = 291), the presence of STAS was not associated with either any (P = 0.50) or distant recurrence (P = 0.76). In a multivariate analysis, the presence of tumor STAS remained independently associated with the risk of developing recurrence (hazard ratio, 3.08; P = 0.014).
The presence of STAS is a significant risk factor of recurrence in small lung adenocarcinomas treated with limited resection. These findings support our proposal that STAS should formally be recognized as a pattern of invasion in lung adenocarcinoma.
Abstract Objective(s) Localization and resection of non-visible, non-palpable pulmonary nodules during video-assisted thoracoscopic surgery (VATS) is challenging. Our study was to determine the ...feasibility and safety of indocyanine green (ICG) fluorescence localization and resection of small nodules using a near-infrared (NIR) fluorescence thoracoscope. Methods Twenty patients with undiagnosed peripheral nodules smaller than 3cm scheduled for CT-guided microcoil placement followed by VATS wedge resection were enrolled. After microcoil deployment, 100-150 μl of diluted ICG was injected percutaneously near the nodule. The nodule was initially localized solely by using the NIR thoracoscope to visualize ICG fluorescence. Thoracoscopic instruments were used to determine the staple line. Wedge resection was performed after confirmation of the location of the microcoil using fluoroscopy. Results Twenty patients underwent NIR image-guided VATS resection. The median CT tumor size was 1.2 cm. The median depth from the pleural surface was 1.4 cm (range: 0.2-4.8). The median CT-guided intervention time was 35 min and VATS procedural time was 54 min. ICG fluorescence was clearly identified in 18 of 20 cases (90%). The surgical margins were all negative on final pathology without the need of additional resection. The final diagnoses included 18 primary lung cancer, 1 metastatic lung cancer, and 1 benign lung tumor. Conclusions CT-guided percutaneous ICG injection and intraoperative NIR localization of small nodules is safe and feasible. It offers surgeons the ease of localization through direct ICG fluorescence imaging without the use of fluoroscopy and may be a complementary technique to preoperative microcoil placement for non-visible, non-palpable intrapulmonary nodules.
To examine the significance of the proposed International Association for the Study of Lung Cancer, American Thoracic Society, and European Respiratory Society (IASLC/ATS/ERS) histologic subtypes of ...lung adenocarcinoma for patterns of recurrence and, among patients who recur following resection of stage I lung adenocarcinoma, for postrecurrence survival (PRS).
We reviewed patients with stage I lung adenocarcinoma who had undergone complete surgical resection from 1999 to 2009 (N = 1,120). Tumors were subtyped by using the IASLC/ATS/ERS classification. The effects of the dominant subtype on recurrence and, among patients who recurred, on PRS were investigated.
Of 1,120 patients identified, 188 had recurrent disease, 103 of whom died as a result of lung cancer. Among patients who recurred, 2-year PRS was 45%, and median PRS was 26.1 months. Compared with patients with nonsolid tumors, patients with solid predominant tumors had earlier (P = .007), more extrathoracic (P < .001), and more multisite (P = .011) recurrences. Multivariable analysis of primary tumor factors revealed that, among patients who recurred, solid predominant histologic pattern in the primary tumor (hazard ratio HR, 1.76; P = .016), age older than 65 years (HR, 1.63; P = .01), and sublobar resection (HR, 1.6; P = .01) were significantly associated with worse PRS. Presence of extrathoracic metastasis (HR, 1.76; P = .013) and age older than 65 years at the time of recurrence (HR, 1.7; P = .014) were also significantly associated with worse PRS.
In patients with stage I primary lung adenocarcinoma, solid predominant subtype is an independent predictor of early recurrence and, among those patients who recur, of worse PRS. Our findings provide a rationale for investigating adjuvant therapy and identify novel therapeutic targets for patients with solid predominant lung adenocarcinoma.
Sentinel lymph node biopsy for lung cancer Gregor, Alexander; Ujiie, Hideki; Yasufuku, Kazuhiro
General thoracic and cardiovascular surgery,
10/2020, Letnik:
68, Številka:
10
Journal Article
Recenzirano
Sentinel lymph node biopsy is a technique to identify the first lymph node (or nodes) draining a tumor. The underlying principle is that as the first site of cancer spread, evaluation of the sentinel ...node will be most predictive for wider nodal involvement. The introduction of sentinel node biopsy revolutionized the surgical management of cutaneous melanoma and breast cancer, becoming a key component in the management of such patients. For over 20 years, thoracic surgeons have similarly worked to apply this technique to lung cancer but have thus far not had the same impact on lung surgery. In this review, we will summarize the ongoing discussions on the role of sentinel node biopsy in lung cancer, the methods for identifying the sentinel node, and the techniques for evaluating the sentinel node specimen. We will also highlight some of the pressing questions investigators should consider when designing a trial for sentinel node mapping. This will clarify the current status of sentinel node biopsy in lung cancer and thus highlight important future directions for research.
Highlights • The high level of KIF23 expression was observed in majority of metastatic lung cancer tissue compared with normal lung control. • KIF23 is crucial for the growth and survival of lung ...cancer cells. • A high level of the KIF23 is strongly associated with poor survival in patients with lung adenocarcinoma. • KIF23 can be valuable for developing new therapeutic targets for advanced lung cancers.
Background Endobronchial ultrasonography (EBUS)-guided transbronchial needle aspiration allows for sampling of mediastinal lymph nodes. The external diameter, rigidity, and angulation of the convex ...probe EBUS renders limited accessibility. This study compares the accessibility and transbronchial needle aspiration capability of the prototype thin convex probe EBUS against the convex probe EBUS in human ex vivo lungs rejected for transplant. Methods The prototype thin convex probe EBUS (BF-Y0055; Olympus, Tokyo, Japan) with a thinner tip (5.9 mm), greater upward angle (170 degrees), and decreased forward oblique direction of view (20 degrees) was compared with the current convex probe EBUS (6.9-mm tip, 120 degrees, and 35 degrees, respectively). Accessibility and transbronchial needle aspiration capability was assessed in ex vivo human lungs declined for lung transplant. The distance of maximum reach and sustainable endoscopic limit were measured. Transbronchial needle aspiration capability was assessed using the prototype 25G aspiration needle in segmental lymph nodes. Results In all evaluated lungs (n = 5), the thin convex probe EBUS demonstrated greater reach and a higher success rate, averaging 22.1 mm greater maximum reach and 10.3 mm further endoscopic visibility range than convex probe EBUS, and could assess selectively almost all segmental bronchi (98% right, 91% left), demonstrating nearly twice the accessibility as the convex probe EBUS (48% right, 47% left). The prototype successfully enabled cytologic assessment of subsegmental lymph nodes with adequate quality using the dedicated 25G aspiration needle. Conclusions Thin convex probe EBUS has greater accessibility to peripheral airways in human lungs and is capable of sampling segmental lymph nodes using the aspiration needle. That will allow for more precise assessment of N1 nodes and, possibly, intrapulmonary lesions normally inaccessible to the conventional convex probe EBUS.
•Evaluated the target-specificity and efficacy of FP-mediated PDT with FOLR1.•FP-mediated image-guided PDT promise therapeutic efficacy with minimal side-effect.•This study can motivate further ...preclinical development and clinical translation.
Despite modest improvements, the prognosis of lung cancer patients has still remained poor and new treatment are urgently needed. Photodynamic therapy (PDT), the use of light-activated compounds (photosensitizers) is a treatment option but its use has been restricted to central airway lesions. Here, we report the use of novel porphyrin-lipid nanoparticles (porphysomes) targeted to folate receptor 1 (FOLR1) to enhance the efficacy and specificity of PDT that may translate into a minimally-invasive intervention for peripheral lung cancer and metastatic lymph nodes of advanced lung cancer.
The frequency of FOLR1 expression in primary lung cancer and metastatic lymph nodes was first analyzed by human tissue samples from surgery and endobronchial ultrasonography-guided transbronchial needle aspiration (EBUS-TBNA). Confocal fluorescence microscopy was then used to confirm the cellular uptake and fluorescence activation in lung cancer cells, and the photocytotoxicity was evaluated using a cell viability assay. In vivo fluorescence activation and quantification of uptake were investigated in mouse lung orthotopic tumor models, followed by the evaluation of in vivo PDT efficacy.
FOLR1 was highly expressed in metastatic lymph node samples from patients with advanced lung cancer and was mainly expressed in lung adenocarcinomas in primary lung cancer. Expression of FOLR1 in lung cancer cell lines corresponded with the intracellular uptake of folate-porphysomes in vitro. When irradiated with a 671nm laser at a dose of 10J/cm2, folate-porphysomes showed marked therapeutic efficacy compared with untargeted porphysomes (28% vs. 83% and 24% vs. 99% cell viability in A549 and SBC5 lung cancer cells, respectively). Systemically-administered folate-porphysomes accumulated in lung tumors with significantly enhanced disease-to-normal tissue contrast. Folate-porphysomes mediated PDT successfully inhibited tumor cell proliferation and activated tumor cell apoptosis.
Folate-porphysome based PDT shows promise in selectively ablating lung cancer based on FOLR1 expression in these preclinical models.
Introduction: Stiff-person syndrome (SPS) is a rare autoimmune neurological disorder. Paraneoplastic SPS associated with malignant tumors such as thymoma occurs in approximately 5% of all SPS cases. ...We present a rare case of thymoma accompanied by SPS successfully treated using surgery.Presentation of Case: A 26-year-old woman presented with lower limbs convulsions and gait disturbance and complained of leg pain. Cerebrospinal fluid and blood test results showed a high level of anti-glutamic acid decarboxylase (GAD) antibodies. Computed tomography showed anterior mediastinal tumor suggestive of a thymoma. She underwent extended thymectomy, and her symptoms gradually improved after surgery. No evidence of recurrent thymoma and SPS has been observed over 44 months.Conclusion: Surgical treatment would be effective for patients with SPS and thymoma.
Azygos vein aneurysm (AVA) is necessary to prevent pulmonary embolism due to the outflow of a thrombus or rupture of the aneurysm. However, there is no established modality to assess the properties ...of AVA. Time-resolved three-dimensional phase-contrast magnetic resonance imaging (4D-flow MRI) has been used to examine the hemodynamics in various fields. We report a case of AVA to evaluate the flow variability and adhesions of surrounding tissues using 4D-flow MRI. The findings of the study suggested aneurysm turbulence and the absence of thrombi. The cine image, which showed a sliding wall synchronized to the heartbeat, indicated no adhesion to the superior vena cava. Based on these results, the thoracoscopic approach was deemed possible preoperatively. Thoracoscopic AVA resection was performed, and the postoperative course was uneventful. This study documented the utility of 4D-flow MRI for a detailed evaluation of AVA.
Diagnosis and resection of indeterminate pulmonary nodules (IPNs) is a growing challenge with increased utilization of chest computed tomography. Photoacoustic (PA) -guided surgical resection with ...local injection of indocyanine green (ICG) may have utility for IPNs that are suspicious for lung cancer. This preclinical study explores the potential of PA imaging (PAI) to detect ICG-labeled tumors.
ICG uptake by H460 lung cancer cells was evaluated in vitro. A phantom study was performed to analyze PA signal intensity according to ICG concentration and tissue thickness/depth using chicken breast. PA signals were measured up to 48 hours after injection of ICG (mixed with 5% agar) into healthy subcutaneous tissue, subcutaneous H460 tumors and right healthy lung in nude mice.
Intracellular ICG fluorescence was detected in H460 cells co-incubated with ICG in vitro. The concentration dependence of the PA signal was logarithmic, and PA signal decline was exponential with increasing tissue depth. The PA signal of 2 mg/mL ICG was still detectable at a depth of 22 mm in chicken breast. The PA signal from ICG mixed with agar was detectable 48 hours post injection into subcutaneous tissue and subcutaneous H460 tumors in nude mice. Similar features of PA signals from ICG-agar in mice lung were obtained.
The results from this preclinical study suggests that PAI of injected ICG-agar may be beneficial for identifying deeply located tumors. These features may be valuable for IPNs.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK