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BACKGROUND: Standard treatment with neoadjuvant nivolumab plus chemotherapy significantly improves outcomes in patients with resectable non-small-cell lung cancer (NSCLC). Perioperative treatment (i.e., neoadjuvant therapy followed by surgery and adjuvant therapy) with nivolumab may further improve clinical outcomes. METHODS: In this phase 3, randomized, double-blind trial, we assigned adults with resectable stage IIA to IIIB NSCLC to receive neoadjuvant nivolumab plus chemotherapy or neoadjuvant chemotherapy plus placebo every 3 weeks for 4 cycles, followed by surgery and adjuvant nivolumab or placebo every 4 weeks for 1 year. The primary outcome was event-free survival according to blinded independent review. Secondary outcomes were pathological complete response and major pathological response according to blinded independent review, overall survival, and safety. RESULTS: At this prespecified interim analysis (median follow-up, 25.4 months), the percentage of patients with 18-month event-free survival was 70.2% in the nivolumab group and 50.0% in the chemotherapy group (hazard ratio for disease progression or recurrence, abandoned surgery, or death, 0.58; 97.36% confidence interval [CI], 0.42 to 0.81; P<0.001). A pathological complete response occurred in 25.3% of the patients in the nivolumab group and in 4.7% of those in the chemotherapy group (odds ratio, 6.64; 95% CI, 3.40 to 12.97); a major pathological response occurred in 35.4% and 12.1%, respectively (odds ratio, 4.01; 95% CI, 2.48 to 6.49). Grade 3 or 4 treatment-related adverse events occurred in 32.5% of the patients in the nivolumab group and in 25.2% of those in the chemotherapy group. CONCLUSIONS: Perioperative treatment with nivolumab resulted in significantly longer event-free survival than chemotherapy in patients with resectable NSCLC. No new safety signals were observed. (Funded by Bristol Myers Squibb; CheckMate 77T ClinicalTrials.gov number, NCT04025879.).
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Terapia Neoadyuvante , Nivolumab , Humanos , Nivolumab/uso terapéutico , Nivolumab/efectos adversos , Nivolumab/administración & dosificación , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/cirugía , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Femenino , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Carcinoma de Pulmón de Células no Pequeñas/cirugía , Carcinoma de Pulmón de Células no Pequeñas/patología , Anciano , Método Doble Ciego , Quimioterapia Adyuvante , Supervivencia sin Progresión , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Adulto , Antineoplásicos Inmunológicos/uso terapéutico , Antineoplásicos Inmunológicos/efectos adversos , Antineoplásicos Inmunológicos/administración & dosificación , Estadificación de Neoplasias , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Inhibidores de Puntos de Control Inmunológico/efectos adversos , NeumonectomíaRESUMEN
In the open-label, phase III CheckMate 816 study (NCT02998528), neoadjuvant nivolumab plus chemotherapy demonstrated statistically significant improvements in event-free survival (EFS) and pathological complete response (pCR) versus chemotherapy alone in patients with resectable non-small-cell lung cancer (NSCLC). Here we report efficacy and safety outcomes in the Japanese subpopulation. Patients with stage IB-IIIA, resectable NSCLC were randomized 1:1 to nivolumab plus chemotherapy or chemotherapy alone for three cycles before undergoing definitive surgery within 6 weeks of completing neoadjuvant treatment. The primary end-points (EFS and pCR) and safety were assessed in patients enrolled at 16 centers in Japan. Of the Japanese patients randomized, 93.9% (31/33) in the nivolumab plus chemotherapy arm and 82.9% (29/35) in the chemotherapy arm underwent surgery. At 21.5 months' minimum follow-up, median EFS was 30.6 months (95% confidence interval [CI], 16.8-not reached [NR]) with nivolumab plus chemotherapy versus 19.6 months (95% CI, 8.5-NR) with chemotherapy; hazard ratio, 0.60 (95% CI, 0.30-1.24). The pCR rate was 30.3% (95% CI, 15.6-48.7) versus 5.7% (95% CI, 0.7-19.2), respectively; odds ratio, 7.17 (95% CI, 1.44-35.85). Grade 3/4 treatment-related adverse events were reported in 59.4% versus 42.9% of patients, respectively, with no new safety signals identified. Neoadjuvant nivolumab plus chemotherapy resulted in longer EFS and a higher pCR rate versus chemotherapy alone in Japanese patients, consistent with findings in the global population. These data support nivolumab plus chemotherapy as a neoadjuvant treatment option in Japanese patients with resectable NSCLC.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/cirugía , Japón , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/cirugía , Terapia Neoadyuvante , Nivolumab/efectos adversosRESUMEN
We fabricated a frequency-modulated continuous-wave light detection and ranging (FMCW LiDAR) chip that integrates a slow-light grating (SLG) beam scanner and an optical interferometer for k-clock generation using silicon photonics. Beam scanning and FMCW light generation were performed simultaneously through a wavelength sweep, while the sweep nonlinearity was compensated by resampling the ranging signal using the k-clock. The interferometer incorporated a 24-cm-long Si waveguide delay line, facilitating ranging up to 7.1 m and the capture of point cloud images. The possibility of ranging longer distances by lengthening the waveguide and increasing the interpolation is discussed.
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PURPOSE: To evaluate the impact of severe acute kidney injury (AKI) on short-term mortality in patients with urosepsis. METHODS: This prospective cohort study evaluated 207 patients with urosepsis. AKI was diagnosed in accordance with the Kidney Disease Improving Global Outcomes criteria, and severe AKI was defined as stage 2 or 3 AKI. Patients were divided into two groups: patients who developed severe AKI (severe AKI group) and patients who did not (control group). The primary endpoint was all-cause mortality within 30 days. The secondary endpoints were 90-day mortality and in-hospital mortality. The exploratory outcomes were the risk factors for severe AKI development. RESULTS: The median patient age was 79 years. Of the 207 patients, 56 (27%) developed severe AKI. The 30-day mortality rate in the severe AKI group was significantly higher than that in the control group (20% vs. 2.0%, respectively; P < 0.001). In the multivariable analysis, performance status and severe AKI were significantly associated with 30-day mortality. The in-hospital mortality and 90-day mortality rates in the severe AKI group were significantly higher than those in the control group (P < 0.001 and P < 0.001, respectively). In the multivariable analysis, age, urolithiasis-related sepsis, lactate values, and disseminated intravascular coagulation were significantly associated with severe AKI development. CONCLUSIONS: Severe AKI was a common complication in patients with urosepsis and contributed to high short-term mortality rates.
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Lesión Renal Aguda , Mortalidad Hospitalaria , Sepsis , Índice de Severidad de la Enfermedad , Infecciones Urinarias , Humanos , Lesión Renal Aguda/mortalidad , Lesión Renal Aguda/etiología , Femenino , Masculino , Sepsis/complicaciones , Sepsis/mortalidad , Anciano , Estudios Prospectivos , Infecciones Urinarias/complicaciones , Infecciones Urinarias/epidemiología , Infecciones Urinarias/mortalidad , Anciano de 80 o más Años , Factores de Tiempo , Estudios de Cohortes , Persona de Mediana Edad , Causas de MuerteRESUMEN
PURPOSE: Despite the importance of abscess lesions in clinical decisions regarding anaerobic bacteremia (AB), their impact on clinical characteristics remains unclear. Herein, we aimed to elucidate the clinical factors associated with AB that were unaccompanied by detectable abscess lesions during the initial phase of infection. METHODS: This was a multicenter retrospective observational study involving patients with culture-proven AB at six tertiary hospitals in Japan between January 2012 and March 2022. Data on clinical characteristics, laboratory and radiological findings were collected, and their associations with the absence of detectable abscess lesions were analyzed. RESULTS: In total, 393 participants were included. Abscess lesions were absent in 42.7% of the entire cohort and detectable in the remaining patients. No differences were identified in the malignancy, severity, or 30-day mortality between patients with and without detectable abscess lesions. Multivariate logistic regression analysis adjusted for age and the modified Charlson comorbidity score revealed that the immunosuppressive status (febrile neutropenia or corticosteroid use), C-reactive protein (CRP) level ≤9.8 mg/dL at onset, and the presence of gram-positive anaerobic rods (GPARs) were independently associated with AB unaccompanied by detectable abscess lesions [odds ratios (ORs) 3.24, 3.00, and 2.81, respectively; p < 0.05]. CONCLUSION: This study elucidated distinctive clinical and microbiological characteristics of AB unaccompanied by detectable abscess lesions, with relatively lower CRP elevation, immunosuppressive status, and GPARs as the causative anaerobes.
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AIM: The efficacy of titratable fixed-ratio combination therapy by a combination preparation of insulin degludec and liraglutide (IDegLira) in Japanese patients with type 2 diabetes, focusing particularly on the change in Fibrosis-4 index (FIB-4), a noninvasive method for the evaluation of liver fibrosis, was investigated. METHODS: As the full analysis set, 113 patients were treated with IDegLira. The patients were categorized into two groups according to the absence (GLP-1RA-naïve group, n = 72) or presence (GLP-1RA-treated group, n = 41) of glucagon-like peptide-1 receptor agonist (GLP-1RA) use before starting IDegLira. The clinical parameters were retrospectively determined over 6 months. RESULTS: The glycated hemoglobin value was significantly reduced in both groups. The bodyweight significantly decreased from 67.4 ± 11.0 kg at baseline to 66.4 ± 11.6 kg at 6 months in the GLP-1RA-naïve group, although it slightly increased in the GLP-1RA-treated group. FIB-4 significantly decreased from 1.60 ± 0.84 at baseline to 1.49 ± 0.74 at 6 months in the GLP-1RA-naïve group. Although FIB-4 significantly increased in the GLP-1RA-treated group, it remained within the low-risk level for liver fibrosis. CONCLUSION: Fixed-ratio combination therapy using IDegLira for the treatment of type 2 diabetes is useful for glycemic control and weight management. In particular, IDegLira may be more effective for lowering FIB-4 than adding unused oral antidiabetic agents or increasing the dose of insulin in GLP-1RA-naïve patients.
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BACKGROUND: The JCOG0804/WJOG4507L single-arm confirmatory trial indicated a satisfactory 10-year prognosis for patients who underwent limited resection for radiologically less-invasive lung cancer. However, only one prospective trial has reported a 10-year prognosis. METHODS: We conducted a multicenter prospective study coordinated by the National Cancer Center Hospital East and Kanagawa Cancer Center. We analyzed the long-term prognosis of 100 patients who underwent limited resection of a radiologically less-invasive lung cancer in the peripheral lung field. We defined radiologically less-invasive lung cancer as lung adenocarcinoma with a maximum tumor diameter of ≤2 cm, tumor disappearance ratio of ≥0.5 and cN0. The primary endpoint was the 10-year local recurrence-free survival. RESULTS: Our patients, with a median age of 62 years, included 39 males. A total of 58 patients were non-smokers; 87 had undergone wide wedge resection and 9 underwent segmentectomy. A total of four cases were converted to lobectomy because of the presence of poorly differentiated components in the frozen specimen or insufficient margin with segmentectomy. The median follow-up duration was 120.9 months. The 10-year recurrence-free survival and overall survival rates of patients with lung cancer were both 96.0%. Following the 10-year long-term follow-up, two patients experienced recurrences at resection ends after wedge resection. CONCLUSIONS: Limited resection imparted a satisfactory prognosis for patients with radiologically less-invasive lung cancer, except two cases of local recurrence >5 years after surgery. These findings suggest that patients with this condition who underwent limited resection may require continued follow-up >5 years after surgery.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Masculino , Humanos , Persona de Mediana Edad , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/cirugía , Carcinoma de Pulmón de Células no Pequeñas/patología , Estudios Prospectivos , Estudios de Seguimiento , Neumonectomía , Pulmón/patología , Estudios Retrospectivos , Estadificación de NeoplasiasRESUMEN
PURPOSE: Given that left upper lobe and right upper and middle lobes share a similar anatomy, segmentectomy, such as upper division and lingulectomy, should yield identical oncological clearance to left upper lobectomy. We compared the prognosis of segmentectomy with that of lobectomy for early stage non-small-cell lung cancer (NSCLC) in the left upper lobe. METHODS: We retrospectively examined 2115 patients who underwent segmentectomy or lobectomy for c-stage I (TNM 8th edition) NSCLC in the left upper lobe in 2010. We compared the oncological outcomes of segmentectomy (n = 483) and lobectomy (n = 483) using a propensity score matching analysis. RESULTS: The 5-year recurrence-free and overall survival rates in the segmentectomy and lobectomy groups were comparable, irrespective of c-stage IA or IB. Subset analyses according to radiological tumor findings showed that segmentectomy yielded oncological outcomes comparable to those of lobectomy for non-pure solid tumors. In cases where the solid tumor exceeded 20 mm, segmentectomy showed a recurrence-free survival inferior to that of lobectomy (p = 0.028), despite an equivalent overall survival (p = 0.38). CONCLUSION: Segmentectomy may be an acceptable alternative to lobectomy with regard to the overall survival of patients with c-stage I NSCLC in the left upper lobe.
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Gastric mixed neuroendocrine-non-neuroendocrine neoplasm (MiNEN) is an extremely rare form of gastric neoplasm, and its prognosis is often poor. This is a case report wherein the primary site increased during chemotherapy against gastric adenocarcinoma and was diagnosed with gastric MiNEN after total gastrectomy. A 71-year-old man was diagnosed with gastric adenocarcinoma complicated with liver and para-aortic lymph node metastasis. Chemotherapy with S-1, oxaliplatin, and trastuzumab was initiated. Although the size of metastatic lesions was reduced after six courses of treatment, a part of the primary site of gastric tumor rapidly. Pathological rebiopsy of the primary site suggested a neuroendocrine carcinoma, and he was finally diagnosed with gastric MiNEN after total gastrectomy. Thus, second-line chemotherapy was then initiated showing good response. We herein report a case of MiNEN with a rare diagnostic process.
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Adenocarcinoma , Carcinoma Neuroendocrino , Tumores Neuroendocrinos , Neoplasias Gástricas , Masculino , Humanos , Anciano , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/cirugía , Neoplasias Gástricas/patología , Tumores Neuroendocrinos/tratamiento farmacológico , Tumores Neuroendocrinos/diagnóstico , Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/cirugía , Carcinoma Neuroendocrino/terapia , BiopsiaRESUMEN
Reverspectives and hollow masks cause a reversal of perceived depth when observed from a position beyond certain critical distances, even if viewed binocularly. Their 3D structures or images invariably contain a linear perspective, shading, or familiarity cue to depth. Using a concave screen, we demonstrate a novel type of perceived depth reversal in binocular viewing with a variety of depth cues.
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Two dots shown in quick succession at one point and a third at a distance on the same linear path creates an illusion of intervening flashes on a visual field, a phenomenon known as the reduced visual rabbit illusion or visual saltation illusion. This study presents this illusion in a novel way by altering the position of the second flash, which has been typically presented only in the same position as the first flash. A series of experiments were conducted to observe whether saltation would occur if the second flash was presented in the same position as the third flash, out of sequential order relative to the first and last flash, or out of linear alignment at the midpoint between the first and the last flash. When all three flashes were presented in quick succession, participants misperceived the second flash to occur close to the midpoint between the first and last flash. Saltation was achieved in all three novel conditions, hinting a particular neurological process may be responsible for shared outcomes.
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Osimertinib is a first-line or adjuvant therapy for non-small cell lung cancer (NSCLC) harboring an epidermal growth factor receptor (EGFR) mutation. However, owing to the adverse events associated with treatment, certain patients cannot maintain a daily regimen of 80 or 40 mg. In this study, we examined the efficacy of 40 mg of osimertinib administered every other day. In this single-center, retrospective study, we evaluated patients with NSCLC harboring an EGFR mutation in whom treatment was initiated with 40 mg osimertinib every other day at our institution between May 2016 and June 2023. The major outcome was the duration of administering 40 mg osimertinib every other day. Six patients with NSCLC were evaluated. The median duration of 40 mg osimertinib intake every other day was 12.6 months. Four of the six patients weighed below 50 kg, and four experienced weight loss. Additionally, four of the six patients had severe renal impairment upon receiving 40 mg osimertinib every other day. Thus, our findings suggest the efficacy of administering 40 mg osimertinib every other day in patients with low bodyweight, weight loss, or severe renal impairment.
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Acrilamidas , Compuestos de Anilina , Carcinoma de Pulmón de Células no Pequeñas , Indoles , Neoplasias Pulmonares , Pirimidinas , Humanos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/inducido químicamente , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/inducido químicamente , Estudios Retrospectivos , Mutación , Receptores ErbB/genética , Inhibidores de Proteínas Quinasas/efectos adversos , Pérdida de PesoRESUMEN
Oryzamutaic acids, possessing a nitrogen-containing heterocyclic skeleton, have been isolated and identified from a rice mutant. Although oryzamutaic acids are expected to be functional ingredients, their functionality is difficult to evaluate, because of their wide variety and presence in trace amounts. Furthermore, how oryzamutaic acid is synthesized in vivo is unclear. Therefore, we developed a simple enzymatic synthesis method for these compounds in vitro. We focused on L-lysine ε-dehydrogenase (LysDH) from Agrobacterium tumefaciens, which synthesizes α-aminoadipate-δ-semialdehyde-a precursor of oryzamutaic acids. LysDH was cloned and expressed in Escherichia coli. Analysis of activity revealed that LysDH catalyzed the synthesis of oryzamutaic acid H at neutral pH in vitro. We synthesized 1.6â¯mg oryzamutaic acid H from 100â¯mgâ¯L-lysine. The synthesized oryzamutaic acid H exhibited UVA absorption, stability of temperature, and stability at a wide pH range. To our knowledge, this study is the first to report the enzymatic synthesis of oryzamutaic acid H in vitro and provides a basis for understanding the mechanisms of oryzamutaic acid synthesis in vivo.
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Agrobacterium tumefaciens , Aminoácido Oxidorreductasas , Agrobacterium tumefaciens/genética , Lisina , ÁcidosRESUMEN
Partial anomalous pulmonary venous return (PAPVR) is a rare congenital malformation where the pulmonary vein partially refluxes into the venous system. Here, we present the first robotic-assisted right S3 segmentectomy in a 70-year-old male with early-stage lung cancer and PAPVR in the right upper pulmonary vein. The patient, with suspected primary lung cancer (11 mm diameter, pure solid appearance in right S3 segment), exhibited clinical stage T1bN0M0 stage IA2. Preoperative computed tomography revealed severe lung emphysema, and right V1-3 returned directly to the superior vena cava. However, no signs of right-sided heart failure were observed, and echocardiogram was normal with a pulmonary-to-systemic blood flow ratio of 1.4. Successful robot-assisted right S3 segmentectomy with hilar nodal dissection was performed, and the patient was discharged on the sixth postoperative day without complications. One year postoperatively, there has been no recurrence of lung cancer or respiratory/right-sided heart failure symptoms.
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Insuficiencia Cardíaca , Neoplasias Pulmonares , Venas Pulmonares , Síndrome de Cimitarra , Masculino , Humanos , Anciano , Venas Pulmonares/cirugía , Venas Pulmonares/anomalías , Síndrome de Cimitarra/diagnóstico por imagen , Síndrome de Cimitarra/cirugía , Vena Cava Superior/cirugía , Neoplasias Pulmonares/cirugía , Neumonectomía , Pulmón , Insuficiencia Cardíaca/cirugíaRESUMEN
BACKGROUND: Previous studies have suggested that response-style strategies (rumination, problem-solving, and distraction) can be risk or protective factors for the development of abnormal eating behaviors/attitudes (AEB) during adolescence. However, due to limited empirical data regarding the prospective effects of these strategies on AEB, further research is needed to clarify their role in developing AEB in adolescence. METHODS: This study investigated the one-year lagged effects of response-style strategies on AEB in 24,883 fourth- to eighth-grade students in Japan between 2015 and 2019 using a cross-lagged panel model. Depressive symptoms and body mass index (BMI), which are reported to relate to AEB, were also included in the analytic model. The students self-reported their levels of response-style strategies, AEB, and depressive symptoms. We also evaluated BMI based on teachers' reports. RESULTS: We found that greater rumination significantly predicted more severe AEB in the following year among students from all grades, with small to moderate effect sizes. In addition, distraction significantly predicted more severe binge eating/purging behaviors, but with very weak small effect sizes. Problem-solving did not predict any level of AEB. Furthermore, we observed significant reciprocal relationships between response-style strategies, AEB, and depressive symptoms. Positive reciprocal associations between BMI and AEB were also found except for some intervals. CONCLUSIONS: We concluded that a decrease in rumination is critical to alleviating mental health problems, such as AEB and depressive symptoms, during adolescence. This suggests that interventions to reduce the level of rumination should be conducted in the early stages of adolescence. TRIAL REGISTRATION NUMBER: Not Applicable.
This study examines the effects of three response styles when faced with distressrumination, problem-solving, and distractionon unhealthy eating behaviors. In this study, we looked at how these coping strategies are linked to unhealthy eating behaviors in 24,883 students in grades four to eight in Japan between 2015 and 2019. We checked again at year-long intervals to see if the coping strategies had any effect on the students' unhealthy eating behaviors. In addition, we considered depressive symptoms and body mass index in our analysis because these variables might also be related to unhealthy eating behaviors. We found that more rumination (i.e., a repetitive negative thinking pattern) predicted the severity of unhealthy eating behaviors and depressive symptoms in the following year across all the grades. In addition, greater depressive symptoms also contributed to an increase in unhealthy eating behaviors in the following year. Therefore, we suggest that rumination is a key factor that influences mental health during adolescence.
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BACKGROUND: The purpose of this study was to determine the optimal extent of lymph node dissection required in patients with small (≤3 cm) radiologically ground-glass opacity-dominant, peripheral, non-small cell lung cancer tumors. METHODS: The study analyzed the clinicopathologic findings and surgical outcomes of 988 patients with radiologic, ground-glass opacity-dominant non-small cell lung cancer without lymph node involvement who underwent complete resection of the primary tumor between 2010 and 2020. Patients were followed up for 54.5 months (median). Kaplan-Meier curves and the log-rank test were used in statistical analyses of the prognosis. RESULTS: Median age, whole tumor size, solid tumor size, and maximum standardized uptake values were 68 years, 1.7 cm, 0.4 cm, and 0.9, respectively. Sixty percent of the cohort was female (n = 590). Wedge resection, segmentectomy, and lobectomy were performed in 206, 372, and 410 patients, respectively. A total of 982 of 988 (99%) tumors were adenocarcinomas. One patient had hilar lymph node involvement; however, no mediastinal lymph node metastasis or hilar or mediastinal lymph node recurrence was detected. The 5-year overall survival rate was 96.5% (95% CI, 94.8%-97.7%). Excellent survival outcomes were achieved regardless of procedure (wedge resection, 94.7% [95% CI, 89.1%-97.5%]; segmentectomy, 96.9% [95% CI, 93.7%-98.5%]; and lobectomy, 97.1% [95% CI, 94.4%-98.5%]). CONCLUSIONS: Omitting lymph node dissection may be acceptable with curative intent for small tumors with radiologic ground-glass opacity dominance. Appropriate surgical procedures such as wedge resection, segmentectomy, or lobectomy can provide satisfactory outcomes in patients with indolent tumors if surgical margins are secured.
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BACKGROUND: Chordoma, a rare malignant tumor arising from notochordal tissue, usually occurs along the spinal axis. Only a few published reports of primary lung chordomas exist. Herein, we present a case of primary lung chordoma and discuss important considerations for diagnosing rare chordomas. CASE PRESENTATION: We report a case of primary lung chordoma in a 39-year-old male with a history of testicular mixed germ-cell tumor of yolk sac and teratoma. Computed tomography revealed slow-growing solid lesions in the left lower lobe. We performed wedge resection for suspected germ-cell tumor lung metastasis. Histologically, large round or oval cells with eosinophilic cytoplasm were surrounded by large cells with granular, lightly eosinophilic cytoplasm. Tumor cells were physaliphorous. Immunohistochemistry was positive for brachyury, S-100 protein, epithelial membrane antigen, vimentin, and cytokeratin AE1/AE3, suggesting pulmonary chordoma. Re-examination of the testicular mixed germ-cell tumor revealed no notochordal elements. Although some areas were positive for brachyury staining, hematoxylin and eosin (HE) staining did not show morphological features typical of chordoma. Complementary fluorescence in situ hybridization (FISH) of the lung tumor confirmed the absence of isochromosome 12p and 12p amplification. Thus, a final diagnosis of primary lung chordoma was established. CONCLUSIONS: In patients with a history of testicular mixed germ cell tumors, comparison of histomorphology using HE and Brachyury staining of lung and testicular tumors, and analyzing isochromosome 12p and 12p amplification in lung tumors using FISH is pivotal for the diagnosis of rare lung chordomas.
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Biomarcadores de Tumor , Cordoma , Neoplasias Pulmonares , Neoplasias de Células Germinales y Embrionarias , Neoplasias Testiculares , Humanos , Masculino , Cordoma/patología , Cordoma/diagnóstico , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/diagnóstico , Adulto , Biomarcadores de Tumor/análisis , Neoplasias de Células Germinales y Embrionarias/patología , Neoplasias de Células Germinales y Embrionarias/química , Neoplasias de Células Germinales y Embrionarias/diagnóstico , Neoplasias Testiculares/patología , Neoplasias Testiculares/diagnóstico , Neoplasias Testiculares/química , Inmunohistoquímica , Hibridación Fluorescente in Situ , Teratoma/patología , Teratoma/química , Teratoma/diagnósticoRESUMEN
The objective of this study was to evaluate the relationship between pathologic response and survival in patients with clinical stage II/IIIA nonsquamous non-small-cell lung cancer (NSCLC) who intended to undergo neoadjuvant chemotherapy with bevacizumab, followed by surgery. In this phase II NAVAL study evaluating the feasibility of neoadjuvant chemotherapy with cisplatin (75 mg/m2), pemetrexed (500 mg/m2), and bevacizumab (15 mg/kg), followed by surgery, progression-free survival (PFS) and overall survival (OS) were assessed as the secondary endpoints. Patients were categorized based on the proportion of residual viable primary tumor in the resected specimen after neoadjuvant chemotherapy: those with residual tumor in less than one-third were classified as pathologic responders, the rest as nonresponders. Of the 30 patients, 25 underwent surgical resection after three cycles of neoadjuvant chemotherapy with bevacizumab; 5 did not undergo surgery. Among all 30 patients, the rates of 2- and 5-year PFS were 41.5% and 34.6%, respectively, and the rates of 2- and 5-year OS were 70.0% and 60.0%, respectively. A total of 6 patients (20%) were classified as pathologic responders; the other 24 (80%), as nonresponders. The five-year PFS differed significantly between pathologic responders (100%) and nonresponders (17.5%; p = 0.002). The five-year OS also differed significantly between pathologic responders (100%) and nonresponders (43.5%; p = 0.006). Pathologic response seems to be a predictor of survival. Long-term survival after surgery is expected for pathologic responders, whereas additional therapy is needed for nonresponders.
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BACKGROUND: Lobectomy is a standard surgical procedure for peripherally located early-stage non-small cell lung cancers (NSCLCs) measuring 2 to 4 cm. However, it is unclear whether sublobar resections, such as wedge resection and segmentectomy, are effective in treating tumors with driver mutations in the epidermal growth factor receptor (EGFR). METHODS: We analyzed the clinicopathologic findings and surgical outcomes of 1395 patients with radiologically solid-dominant NSCLC measuring 2 to 4 cm, without clinical lymph node involvement, who underwent complete resection between 2010 and 2020. The patients, who underwent sublobar resections (n = 231) or lobectomy (n = 1164), were categorized by their EGFR mutation status and the surgical procedures performed. The follow-up was conducted for a median of 45.3 months. RESULTS: The 5-year overall survival (OS) rates after sublobar resections (n = 39) were comparable to those after lobectomy (n = 359) in patients with EGFR mutation-positive tumors (80.5% [95% CI, 51.3%-93.2%] vs 88.8% [95% CI, 84.1%-92.1%], respectively; P = .16). Multivariable Cox regression analysis of OS revealed that the surgical procedure was an independent prognostic predictor in the entire cohort (hazard ratio, 0.6; 95% CI, 0.4-1.0; P = .028), but it was not an independent prognostic predictor in patients with EGFR-mutated tumors (hazard ratio, 0.6; 95% CI, 0.2-1.7; P = .32). CONCLUSIONS: Sublobar resection with a secure surgical margin could be a viable option for appropriately selected patients with peripheral early-stage NSCLC tumors measuring 2 to 4 cm and harboring EGFR mutations, because it provides comparable OS to that of lobectomy.
Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Receptores ErbB , Neoplasias Pulmonares , Mutación , Neumonectomía , Humanos , Carcinoma de Pulmón de Células no Pequeñas/cirugía , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Carcinoma de Pulmón de Células no Pequeñas/patología , Neoplasias Pulmonares/cirugía , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/mortalidad , Masculino , Receptores ErbB/genética , Femenino , Neumonectomía/métodos , Persona de Mediana Edad , Anciano , Estudios Retrospectivos , Estadificación de Neoplasias , Tasa de Supervivencia/tendencias , AdultoRESUMEN
Background: In flexible bronchoscopy, endobronchial ultrasonography using a guide sheath (EBUS-GS) has varying diagnostic yield depending on the findings of radial-endobronchial ultrasonography (R-EBUS). The diagnosis rate is lower when the ultrasound probe is "adjacent to", than when it is "within" the lesion. However, these findings are inconsistent, and the imaging status may change from "adjacent to" to "within" as examination progresses. In this study, we analyzed the predictive factors for this change, which remain unexplored till date. Methods: Patients who underwent flexible bronchoscopic biopsy with EBUS-GS at Kameda Medical Centre between 1 April 2014 and 31 March 2019 were included in this retrospective cohort study. Patients without "adjacent to" lesions were excluded. The appearance of "A to W" (the change from "adjacent to" to "within" imaging status) was the primary outcome. Based on multivariate regression and receiver operating characteristic curve analysis, we evaluated the discriminative properties of the factors strongly correlated with "A to W". Results: In total, 260 patients were included in this study. In 84 cases, the R-EBUS findings were "A to W". No such findings were observed in 176 cases. The mean lesion diameter was significantly larger (P=0.021) in the group with "A to W" than in the group without. The odds ratio [1.023 (1.003-1.046)] for lesion diameter showed statistical significance in the multivariable regression model. The sensitivity and specificity were 0.346 and 0.852, respectively, at the optimal threshold (29.25 mm) set using the Youden index. Conclusions: We found that lesion diameter was a significant factor in predicting "A to W", with a cut-off value of 29.25 mm and high specificity (0.852).