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1.
Pathol Res Pract ; 262: 155557, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39191195

RESUMEN

Emerin and lamins not only influence nuclear morphology but are also involved in differentiation. We herein examined 82 resected cases of invasive lung adenocarcinoma using computer-assisted image analysis of nuclear morphology on Feulgen-stained and immunohistochemical sections of lamin A, B1, B2, and emerin (four proteins) to calculate the rank sum of the cell positivity rates for these four proteins. The rank sum of four proteins showed weak negative correlations with the nuclear area and perimeter and a weak positive correlation with the nuclear shape factor. Interestingly, the top three cases with the highest rank sum were papillary adenocarcinoma, and the bottom three cases were acinar adenocarcinomas containing cribriform patterns. We compared the rank sum for grading (differentiation: G1, G2, and G3) and predominant histological subtypes and found that the rank sum of G3 was lower than that of G1 and G2. Furthermore, the rank sum was lower for acinar adenocarcinoma with >20 % cribriform pattern (acinar+cribri) and solid adenocarcinoma than for lepidic and papillary adenocarcinoma. Individual examination of the four proteins revealed that emerin expression was lower in G3 than in G1, and lamin B2 expression was lower in G3 than in G1 and G2. Compared with lepidic adenocarcinoma, acinar+cribri showed significantly lower expression of all four proteins among histological subtypes. These data indicated that the expression of lamin A, B1, B2, and emerin was markedly decreased in poorly differentiated adenocarcinoma (i.e., G3), especially in acinar+cribri. Our data suggested that changes in these four proteins can not only affect nuclear morphology but also histological structure in lung adenocarcinoma.


Asunto(s)
Adenocarcinoma del Pulmón , Neoplasias Pulmonares , Proteínas de la Membrana , Proteínas Nucleares , Humanos , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/metabolismo , Adenocarcinoma del Pulmón/patología , Adenocarcinoma del Pulmón/metabolismo , Masculino , Proteínas de la Membrana/metabolismo , Proteínas de la Membrana/análisis , Femenino , Persona de Mediana Edad , Anciano , Proteínas Nucleares/metabolismo , Proteínas Nucleares/análisis , Adenocarcinoma/patología , Adenocarcinoma/metabolismo , Núcleo Celular/patología , Núcleo Celular/metabolismo , Biomarcadores de Tumor/análisis , Biomarcadores de Tumor/metabolismo , Laminas/metabolismo , Adulto , Anciano de 80 o más Años
2.
Thorac Cancer ; 15(11): 859-866, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38414316

RESUMEN

BACKGROUND: Regional lymph node recurrence after radical surgery for non-small cell lung cancer (NSCLC) is an oligo-recurrent disease; however, no treatment strategy has been established. In the present study we aimed to determine the clinical outcomes of postoperative regional lymph node recurrence and identify prognostic predictors in the era of molecular-targeted therapy. METHODS: We retrospectively analyzed data on clinical characteristics and outcomes of patients with regional lymph node recurrence after surgery who underwent treatment for NSCLC between 2002 and 2022. RESULTS: A total of 53 patients were included in this study. The median time between surgery and detection of recurrence was 1.21 years. Radiotherapy (RT) alone and chemoradiotherapy (CRT) were performed in 38 and six patients, respectively. Driver gene alterations were detected in eight patients (EGFR: 6, ROS1:1, and BRAF: 1) and programmed death-ligand 1 (PD-L1) expression was examined in 22 patients after 2016. Median progression-free survival (PFS) and overall survival (OS) after lymph node recurrences were 1.32 and 4.34 years, respectively. Multiple lymph node recurrence was an independent prognostic factor for PFS, whereas driver gene alteration was the only prognostic factor for OS. There was no significant difference in the OS between patients stratified according to the initial treatment modality for lymph node recurrence. CONCLUSION: Our results suggest that the number of tumor recurrences may correlate with PFS, while detection of driver gene alterations could guide decision-making for the appropriate molecular-targeted therapy to achieve longer OS.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/cirugía , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/cirugía , Estudios Retrospectivos , Proteínas Tirosina Quinasas , Recurrencia Local de Neoplasia/patología , Proteínas Proto-Oncogénicas , Pronóstico , Ganglios Linfáticos/patología
3.
Thorac Cancer ; 15(2): 131-141, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38014454

RESUMEN

BACKGROUND: Molecular abnormalities in the Wnt/ß-catenin pathway confer malignant phenotypes in lung cancer. Previously, we identified the association of leucine-rich repeat-containing G protein-coupled receptor 6 (LGR6) with oncogenic Wnt signaling, and its downregulation upon ß-catenin knockdown in non-small cell lung cancer (NSCLC) cells carrying CTNNB1 mutations. The aim of this study was to explore the mechanisms underlying this association and the accompanying phenotypes. METHODS: LGR6 expression in lung cancer cell lines and surgical specimens was analyzed using quantitative RT-PCR and immunohistochemistry. Cell growth was assessed using colony formation assay. Additionally, mRNA sequencing was performed to compare the expression profiles of cells subjected to different treatments. RESULTS: LGR6 was overexpressed in small cell lung cancer (SCLC) and NSCLC cell lines, including the CTNNB1-mutated NSCLC cell lines HCC15 and A427. In both cell lines, LGR6 knockdown inhibited cell growth. LGR6 expression was upregulated in spheroids compared to adherent cultures of A427 cells, suggesting that LGR6 participates in the acquisition of cancer stem cell properties. Immunohistochemical analysis of lung cancer specimens revealed that the LGR6 protein was predominantly overexpressed in SCLCs, large cell neuroendocrine carcinomas, and lung adenocarcinomas, wherein LGR6 overexpression was associated with vascular invasion, the wild-type EGFR genotype, and an unfavorable prognosis. Integrated mRNA sequencing analysis of HCC15 and A427 cells with or without LGR6 knockdown revealed LGR6-related pathways and genes associated with cancer development and stemness properties. CONCLUSIONS: Our findings highlight the oncogenic roles of LGR6 overexpression induced by aberrant Wnt/ß-catenin signaling in lung cancer.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/patología , Vía de Señalización Wnt/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , beta Catenina/genética , beta Catenina/metabolismo , ARN Mensajero , Línea Celular Tumoral , Proliferación Celular , Receptores Acoplados a Proteínas G/genética
4.
Intern Med ; 2023 Oct 13.
Artículo en Inglés | MEDLINE | ID: mdl-37839880

RESUMEN

A 75-year-old man underwent chemoradiotherapy for advanced esophageal cancer. After nine years, he was hospitalized for left pyothorax. Consequently, the patient underwent drainage and window opening surgery. He experienced cardiopulmonary arrest but was resuscitated. Based on cardiac catheterization data, the patient was diagnosed with constrictive pericarditis. Unfortunately, extracorporeal circulation did not improve his condition, and he ultimately died. An autopsy revealed adhesion between the pericardium and pleura, especially the pericardium in contact with the left thoracic cavity, which was markedly thickened. This suggests that constrictive pericarditis, a latent complication of chemoradiotherapy, is aggravated by pyothorax.

5.
Surg Case Rep ; 9(1): 68, 2023 May 03.
Artículo en Inglés | MEDLINE | ID: mdl-37133711

RESUMEN

BACKGROUND: Thymoma is associated with autoimmune diseases. Myasthenia gravis is frequently associated with thymoma, but cases of thymoma complicated by alopecia areata are very rare. In this report, we present a case of thymoma associated with alopecia areata, but without Myasthenia gravis. CASE PRESENTATION: A 60-year-old woman had a complaint of rapid progression of alopecia areata. A hair follicular biopsy was performed, which showed the infiltration of CD8-positive lymphocytes. She was prescribed topical steroids for 2 months prior to surgery, but her hair loss was not improved. Screening computed tomography showed a mass in the anterior mediastinum, which was suspected to be a thymoma. Myasthenia gravis was ruled out because she had no relevant symptoms or physical findings, and no anti-acetylcholine receptor antibodies were detected in serum. We performed a transsternal extended thymectomy based on a diagnosis of thymoma Masaoka stage I, without myasthenia gravis. Pathological examination showed Type AB thymoma, Masaoka stage II. The chest drainage tube was removed on postoperative day 1, and the patient was discharged on postoperative day 6. The patient has continued topical steroids and showed improvement 2 months postoperatively. CONCLUSIONS: Although alopecia areata is a rare complication in thymoma cases without myasthenia gravis, thoracic surgeons need to keep this condition in mind because alopecia reduces the patient's quality of life.

6.
J Thorac Dis ; 15(3): 1009-1017, 2023 Mar 31.
Artículo en Inglés | MEDLINE | ID: mdl-37065586

RESUMEN

Background: Late-onset pulmonary fistula (LOPF) is a well-described complication after segmentectomy, but the precise incidence and risk factors are still unclear. We aimed to determine the incidence of, and risk factors for, LOPF development after segmentectomy. Methods: A single-institution retrospective study was performed. A total of 396 patients who underwent segmentectomy were enrolled. Perioperative data were analyzed to identify the risk factors for LOPF requiring readmission according to univariate and multivariate analyses. Results: The overall morbidity rate was 19.4%. The incidence rates of prolonged air leak (PAL) in the early phase and LOPF in the late phase were 6.3% (25/396) and 4.5% (18/396), respectively. The most common surgical procedures with LOPF development were segmentectomy of the upper-division (n=6) and S6 (n=5). With a univariate analysis, presence of smoking-related diseases did not affect LOPF development (P=0.139). Conversely, segmentectomy with cranial side free space (CSFS) in the intersegmental plane and use of electrocautery to divide the intersegmental plane were associated with a high risk of LOPF development (P=0.006 and 0.009, respectively). A multivariate logistic regression analysis showed that segmentectomy with CSFS in the intersegmental plane and use of electrocautery were independent risk factors for LOPF development. Approximately 80% of patients who developed LOPF recovered by prompt drainage and pleurodesis without reoperation, whereas the remaining patients developed empyema due to delayed drainage. Conclusions: Segmentectomy with CSFS is an independent risk factor for LOPF development. Careful postoperative follow up and rapid treatment are necessary to avoid empyema.

7.
J Thorac Dis ; 15(3): 1075-1085, 2023 Mar 31.
Artículo en Inglés | MEDLINE | ID: mdl-37065588

RESUMEN

Background: Segmentectomy is a standard procedure, and there is considerable data on routine segmentectomies. However, there are only few reports on lobectomy performed in combination with segmentectomy (lobectomy + segmentectomy). Thus, we aimed to clarify the clinicopathological features and surgical outcomes of lobectomy + segmentectomy. Methods: We reviewed patients who underwent lobectomy + segmentectomy between January 2010 and July 2021 at Gunma University Hospital, Japan. We comparatively analyzed clinicopathological data of patients who underwent lobectomy + segmentectomy and those who underwent lobectomy in combination with wedge resection (lobectomy + wedge resection). Results: We collected data from 22 patients who underwent lobectomy + segmentectomy and 72 who underwent lobectomy + wedge resection. Lobectomy + segmentectomy was mainly performed to treat lung cancer, and the median number of resected segments was 4.5 and the median number of lesions was 2. Lobectomy + segmentectomy was associated with a higher rate of thoracotomy and a longer operation time. Incidence of overall complications, including pulmonary fistula and pneumonia was higher in the lobectomy + segmentectomy group. However, there were no significant differences in the length of drainage, major complications, and mortality. For lobectomy + segmentectomy, the only left-sided procedure was a left lower lobectomy + lingulectomy, whereas procedures were diverse on the right side, mostly combining a right upper or middle lobectomy with atypical segmentectomies. Conclusions: Lobectomy + segmentectomy was performed for (I) multiple lung lesions, (II) lesions invading an adjacent lobe, or (III) lesions with a metastatic lymph node invading the bronchial bifurcation. Although lobectomy + segmentectomy is a lung-preserving procedure that can benefit patients with multiple or advanced diseases involving two lobes, this procedure should still be performed following a careful patient selection process.

8.
Anticancer Drugs ; 34(4): 605-608, 2023 04 01.
Artículo en Inglés | MEDLINE | ID: mdl-36729850

RESUMEN

Lenvatinib is a multitargeted kinase inhibitor and maintaining its dose intensity has been shown to be beneficial in patients with thyroid and hepatocellular carcinomas. However, most patients require lenvatinib interruption and dose reduction due to the high incidence of adverse events (AEs). Lenvatinib was recently approved in Japan for patients with unresectable thymic carcinoma; however, real-world evidence of its clinical benefit is limited. Here, we report the case of chemotherapy-refractory thymic carcinoma in a patient who was administered a starting dose of lenvatinib using a 5-day on/2-day off (weekend-off) protocol, followed by alternate-day administration after fatigue onset derived from overt or subclinical hypothyroidism. Consequently, the patient exhibited a durable response to lenvatinib, with a 17-month progression-free survival without any severe or intolerable AEs. The present case suggests that maintaining lenvatinib dose intensity using such alternative administration regimens contributes to favorable clinical outcomes in thymic carcinoma.


Asunto(s)
Antineoplásicos , Carcinoma Hepatocelular , Neoplasias Hepáticas , Quinolinas , Timoma , Neoplasias del Timo , Humanos , Timoma/tratamiento farmacológico , Timoma/inducido químicamente , Antineoplásicos/uso terapéutico , Compuestos de Fenilurea/uso terapéutico , Carcinoma Hepatocelular/patología , Quinolinas/uso terapéutico , Neoplasias Hepáticas/patología , Neoplasias del Timo/tratamiento farmacológico , Neoplasias del Timo/inducido químicamente
9.
J Cardiothorac Surg ; 17(1): 265, 2022 Oct 10.
Artículo en Inglés | MEDLINE | ID: mdl-36217204

RESUMEN

BACKGROUND: Resection of lung cancer with chest wall involvement is an invasive procedure. CASE PRESENTATION: We report a case of pulmonary adenocarcinoma with chest wall involvement that was resected through video-assisted thoracoscopic segmentectomy and combined en bloc resection of the chest wall (2nd to 4th ribs). Surgical stress was decreased by reducing the extent of lung parenchymal resection and applying a video-assisted technique with an additional posterior paravertebral incision. CONCLUSION: A thoracoscopic surgical approach involving incisions in areas requiring resection of the proximal, lateral, and posterior sides of the involved ribs can be applied to tumors invading the chest wall.


Asunto(s)
Neoplasias Pulmonares , Pared Torácica , Humanos , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/cirugía , Neumonectomía/métodos , Costillas/cirugía , Cirugía Torácica Asistida por Video/métodos , Pared Torácica/patología , Pared Torácica/cirugía
10.
Thorac Cancer ; 13(22): 3225-3228, 2022 11.
Artículo en Inglés | MEDLINE | ID: mdl-36193787

RESUMEN

Epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors are standard therapeutic agents for non-small cell lung cancer (NSCLC) patients with major EGFR mutations such as exon 19 deletions and a L858R mutation, whereas treatment strategies for cases with uncommon EGFR mutations remain to be fully established. Here, we report a long-term (≥20 years from initial diagnosis) NSCLC survivor carrying EGFR L858R and L747V mutations. The patient received gefitinib monotherapy, systemic chemotherapy/chemoimmunotherapy, and local consolidative therapies for oligometastatic lesions, and responded to afatinib rechallenge with a progression-free survival of 12 months. The current case suggests that afatinib is effective in NSCLC patients with EGFR L858R and L747V mutations and that a therapeutic approach combining appropriately timed systemic therapies with local consolidative therapies for oligometastatic lesions improves long-term survival.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Afatinib/farmacología , Afatinib/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Receptores ErbB , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Inhibidores de Proteínas Quinasas/farmacología , Inhibidores de Proteínas Quinasas/uso terapéutico , Mutación , Sobrevivientes
11.
Mol Carcinog ; 61(10): 924-932, 2022 10.
Artículo en Inglés | MEDLINE | ID: mdl-35848137

RESUMEN

The genetic concordance and heterogeneity of the two components of pulmonary carcinosarcoma (PCS), carcinoma, and sarcoma, have not been fully elucidated because of its rare occurrence. We performed targeted sequencing of the carcinoma and sarcoma components of four PCSs to identify genetic similarities and differences. Formalin-fixed paraffin-embedded tissue samples were macroscopically or microscopically dissected. DNA was extracted from each component, and genetic alterations were analyzed separately. Moreover, we performed RNA-seq analysis on both components of one PCS to compare differences in gene expression profiles. The carcinoma part consisted of adenocarcinoma in two cases, squamous cell carcinoma in one, and adenosquamous carcinoma in the last. TP53 mutation was observed in three samples from the trunk, although it was detected only in the sarcoma part in one case. No specific driver gene mutation was observed; however, KRAS mutations were observed in one case in the trunk. RNA-seq analysis revealed that the rhabdomyosarcoma component expressed various genes related to muscle development, whereas the carcinoma component did not; and that gene expression overall was completely different between the two components. Our study revealed that the two different components of PCS shared common gene mutations in most cases. Although gene expression was different among components, if driver genes such as KRAS were detected in PCS, molecular targeted therapy could be beneficial even when the tumor contains a sarcoma component.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Carcinoma de Células Escamosas , Carcinosarcoma , Neoplasias Pulmonares , Sarcoma , Carcinoma de Células Escamosas/genética , Carcinosarcoma/genética , Carcinosarcoma/metabolismo , Carcinosarcoma/patología , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Mutación , Proteínas Proto-Oncogénicas p21(ras)/genética , Proteínas Proto-Oncogénicas p21(ras)/metabolismo
12.
Ann Surg Oncol ; 29(11): 7149-7162, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-35644860

RESUMEN

BACKGROUND: Fibroblast growth factor receptor (FGFR)-signaling in lung squamous cell carcinoma (LSCC) is associated with cancer aggressiveness and poor prognosis. Small GTPase RAB11A regulates the recycling of membrane proteins such as FGFR. This study evaluated the potential of RAB11A as a new therapeutic target for LSCC through its regulation of FGFR-signaling. METHODS: Immunohistochemical analysis of 84 LSCC samples was performed to determine the correlation between RAB11A expression, clinicopathologic features, and prognosis. Alterations in FGFR-signaling were assessed in RAB11A-suppressed and RAB11A-overexpressed LSCC cells both in vitro and in vivo. RESULTS: The study identified RAB11A as a strong predictor of poor prognosis in the LSCC cohort. Cell proliferation and invasion were promoted and inhibited respectively in RAB11A-overexpressed and RAB11A -suppressed LSCC cells. In RAB11A-overexpressed and RAB11A-suppressed LSCC cells, FGFR-signaling was respectively up- and downregulated. The viability of the cells treated with nintedanib and lenvatinib was greater in RAB11A-overexpressing cells than in control cells. The in vivo tumor growth and micro-vessel density of RAB11A-overexpressing tumors were significantly higher than in the control cells. CONCLUSION: As a potentially valuable prognostic marker, RAB11A is a promising therapeutic target for LSCC. Evaluation of RAB11A may be useful for identification of LSCC in patients whose cancer is refractory to FGFR inhibitors.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Carcinoma de Células Escamosas , Neoplasias Laríngeas , Neoplasias Pulmonares , Proteínas de Unión al GTP Monoméricas , Proteínas de Unión al GTP rab , Carcinoma de Células Escamosas/patología , Línea Celular Tumoral , Proliferación Celular , Regulación Neoplásica de la Expresión Génica , Humanos , Neoplasias Laríngeas/patología , Pulmón/metabolismo , Neoplasias Pulmonares/genética , Proteínas de Unión al GTP Monoméricas/metabolismo , Proteínas de Unión al GTP Monoméricas/uso terapéutico , Receptores de Factores de Crecimiento de Fibroblastos/metabolismo , Receptores de Factores de Crecimiento de Fibroblastos/uso terapéutico
13.
Sci Rep ; 12(1): 10589, 2022 06 22.
Artículo en Inglés | MEDLINE | ID: mdl-35732684

RESUMEN

The lateral costal artery and vein are under recognized yet potentially important vessels for physicians, especially cardiothoracic surgeons. This study sought to determine the prevalence and clinical, anatomical, and radiological features of lateral costal vessels. We retrospectively analyzed lateral costal vessels based on intraoperative images in patients who underwent thoracic surgery at our institute between January 2016 and March 2020. Clinical data and surgical videos were analyzed for patient characteristics, prevalence, length, laterality, and additional anatomical and radiological features. The overall prevalence of lateral costal vessels was 19% and was significantly higher in males than females (22% vs. 14%, p = 0.003). The lateral costal vessels extended beyond the 2nd intercostal space in 74% of the cases, with differing length between the right and left sides in bilateral cases. Lateral costal vessels could be identified intraoperatively using indocyanine green or preoperatively through three-dimensional computed tomography. The prevalence of lateral costal vessels is relatively high and should be acknowledged by physicians prior to procedures involving the vessels.


Asunto(s)
Costillas , Venas , Arterias/diagnóstico por imagen , Femenino , Humanos , Masculino , Estudios Retrospectivos , Tomografía Computarizada por Rayos X
14.
Gen Thorac Cardiovasc Surg ; 70(11): 962-970, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-35437709

RESUMEN

BACKGROUND: Lung segmentectomy is an option for the treatment of noninvasive or minimally invasive lung cancer. For tumors located in the left upper division (LUD), LUD trisegmentectomy (S1+2 + S3) is frequently performed as a sublobar resection because of its technical simplicity. However, the differences in surgical outcomes between simple and complex segmentectomies remain unclear. METHODS: We compared the surgical outcomes and frequency of postoperative complications of LUD trisegmentectomy (simple group) with those of complex segmentectomy (other than LUD trisegmentectomy; complex group) for pulmonary lesions using three-dimensional computed tomography between 2010 and 2021. RESULTS: In total, 118 patients were included: 65 in the simple group and 53 in the complex group (S1+2: 25, S3: 15, others: 13). There were no significant differences in surgical time or duration of postoperative chest drainage. However, the blood loss volume was significantly smaller in the complex group than in the simple group (12 vs. 36 mL, p = 0.023), and major complications tended to occur less frequently in the complex group than in the simple group (3.8 vs. 13.8%, p = 0.061). Among patients who underwent intentional segmentectomy for primary lung cancer (n = 61), major complications were significantly less common in the complex group (p = 0.006). CONCLUSIONS: Complex segmentectomy can be performed safely under the guidance of three-dimensional CT. Complex segmentectomy itself is not a risk factor for postoperative complications when the intersegmental planes are sufficiently recognized and accurately cut.


Asunto(s)
Neoplasias Pulmonares , Neumonectomía , Humanos , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/cirugía , Neoplasias Pulmonares/complicaciones , Mastectomía Segmentaria/efectos adversos , Neumonectomía/efectos adversos , Neumonectomía/métodos , Complicaciones Posoperatorias/etiología , Estudios Retrospectivos , Resultado del Tratamiento
15.
Immunol Res ; 70(3): 414-418, 2022 06.
Artículo en Inglés | MEDLINE | ID: mdl-35288824

RESUMEN

Thymoma-associated multiorgan autoimmunity (TAMA) is a rare autoimmune disorder associated with thymoma that causes a pathology similar to graft-versus-host disease (GVHD) targeting the skin, digestive organs, and liver. Herein, we report the case of a 38-year-old male with myasthenia gravis (MG) preceded by TAMA. The patient developed intractable diarrhea 2 years before admission. Subsequently, dysphagia, dysarthria, and left blepharoptosis were observed. The patient was admitted to the hospital because of fever and dyspnea, was positive for anti-AChR antibody, and chest-computed tomography revealed thymoma, which led to the diagnosis of thymoma-related MG. Biopsied specimens from the sigmoid colon revealed apoptotic colonopathy with lymphocyte-rich lamina propria. Immunohistochemical staining revealed that the infiltrating cells were predominantly labeled with anti-CD3-antibody. The patient did not show skin lesions or liver dysfunction. Therefore, TAMA limited to the gastrointestinal tract was diagnosed. Although TAMA typically has a poor prognosis, immediate multimodal immunotherapy for MG was successful, resulting in a good outcome for TAMA of this case. TAMA is caused by the inability of the thymoma to suppress self-reactive T lymphocytes, which subsequently leads to a disease that is clinically indistinguishable from GVHD. Based on the characteristics of this case, limited gastrointestinal tract involvement in TAMA without lesions in other organs may lead to a favorable prognosis. TAMA cases lacking skin lesions may present with nonspecific gastrointestinal or liver disease. If a patient with thymoma-associated MG has gastrointestinal symptoms such as diarrhea, TAMA should be considered, and the diagnosis should be made early by pathological evaluation of gastrointestinal tissues.


Asunto(s)
Enfermedad Injerto contra Huésped , Miastenia Gravis , Timoma , Neoplasias del Timo , Adulto , Autoinmunidad , Diarrea/complicaciones , Enfermedad Injerto contra Huésped/terapia , Humanos , Inmunoterapia , Masculino , Miastenia Gravis/complicaciones , Miastenia Gravis/terapia , Timoma/complicaciones , Timoma/terapia , Neoplasias del Timo/complicaciones , Neoplasias del Timo/terapia
16.
J Thorac Dis ; 14(1): 113-122, 2022 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-35242373

RESUMEN

BACKGROUND: Segmentectomy is now a common treatment option for both lung cancer and metastatic lung tumors with increasing data and evidence. However, data on multiple segmentectomy of different lobes are scarce. Our objective was to clarify the clinicopathological features of multiple segmentectomy. METHODS: We reviewed patients who underwent segmentectomy between January 2010 and December 2019 at Gunma University Hospital. Multiple segmentectomy was defined as segmentectomy of different lobes during the same operation, in contrast to single segmentectomy, which was defined as segmentectomy of a single lobe. Clinicopathologic, operative, and postoperative results were compared between multiple segmentectomy and single segmentectomy. RESULTS: There were 324 patients who underwent single segmentectomy and 11 patients (12 cases) who underwent multiple segmentectomy. Multiple segmentectomy was mostly performed for treatment of metastatic lesions rather than lung cancer. The median number of resected segments was 1 (range, 1-5) in the single segmentectomy group and 3 (range, 2-4) in the multiple segmentectomy group. The median number of resected lung lesions was 3.5 in the multiple segmentectomy group. Multiple segmentectomy was associated with longer operative time, more bleeding, and longer drainage period and postoperative stay than the single segmentectomy group. There were no significant differences in severe complications as well as 30- and 90-day mortality. CONCLUSIONS: Multiple segmentectomy is a lung-preserving procedure that can be considered for patients with multiple lung lesions and has feasible postoperative outcomes.

17.
Ann Thorac Surg ; 113(2): e141-e144, 2022 02.
Artículo en Inglés | MEDLINE | ID: mdl-33945813

RESUMEN

Although segmentectomy has become a routine procedure, atypical segmentectomies are less popular than their typical counterparts, probably because anatomic and surgical data are lacking. The left superior lingular S4 segment is considered relatively small, usually resected along with other segments. However S4 segment size varies among patients, and resection of this single segment can be a valuable lung-preserving procedure in carefully selected patients with tumors located at the border of the upper division and lingular segments. We present here the anatomic and surgical features required for a methodologic left S4 segmentectomy based on our experience and the literature.


Asunto(s)
Neoplasias Pulmonares/cirugía , Pulmón/cirugía , Neumonectomía/métodos , Humanos , Pulmón/diagnóstico por imagen , Neoplasias Pulmonares/diagnóstico , Persona de Mediana Edad , Tomografía Computarizada por Rayos X
18.
Thorac Cancer ; 12(20): 2666-2679, 2021 10.
Artículo en Inglés | MEDLINE | ID: mdl-34453496

RESUMEN

OBJECTIVES: Various drug-sensitivity markers have been reported to be associated with tumor progression and chemotherapy resistance. Detailed expression profiles of sensitivity markers for cytotoxic chemotherapy in pulmonary large cell neuroendocrine carcinoma (LCNEC) remain unclear. Herein, we aimed to clarify the correlation between the expression of drug-sensitivity markers and clinicopathological features, prognostic impact, and status of tumor immunity in patients with LCNEC. METHODS: We retrospectively analyzed the correlation between clinicopathological features and the expression of drug-sensitivity-related markers, including vascular endothelial growth factor 2 (VEGFR2), thymidylate synthase (TS), tubulin beta 3 class III (TUBB3), topoisomerase I (Topo-I), and Topo-II in 92 surgically resected LCNEC samples. Furthermore, we examined the prognostic significance of expression of these and their correlation with the immune cell status. RESULTS: Overall, high expression of TS, TUBB3, VEGFR2, Topo-I, and Topo-II was detected in 50 (54%), 31 (34%), 23 (25%), 65 (71%), and 36 (39%) samples, respectively. Univariate and multivariate analyses revealed that advanced pathological T and N factors, positive lymphatic permeation, and Topo-II expression were independent unfavorable prognosticators for recurrence-free survival, and advanced pathological T and N factors, Topo-II positive expression, and TS positive expression were independent unfavorable prognosticators for overall survival. In terms of correlation with immune cell status, higher expression of VEGFR2 was closely linked to negative PD-L1 expression. CONCLUSIONS: These findings suggest that elevated Topo-II and TS expression may contribute to poor outcomes through protumoral biology in patients with LCNEC, and elevated VEGFR2 expression might negatively impact tumor immune reactions in LCNEC.


Asunto(s)
Carcinoma Neuroendocrino/tratamiento farmacológico , ADN-Topoisomerasas/metabolismo , Neoplasias Pulmonares/tratamiento farmacológico , Timidilato Sintasa/metabolismo , Tubulina (Proteína)/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos/uso terapéutico , Biomarcadores de Tumor/metabolismo , Supervivencia sin Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos
19.
Lung Cancer ; 153: 108-116, 2021 03.
Artículo en Inglés | MEDLINE | ID: mdl-33482408

RESUMEN

OBJECTIVES: The prognostic impact of surgical intervention for recurrent or residual non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutation or anaplastic lymphoma kinase (ALK) rearrangement after tyrosine-kinase inhibitor (TKI) treatment remains unclear. We aimed to describe the characteristics and outcomes of patients undergoing salvage surgery in this setting. METHODS: We retrospectively collected and analyzed nationwide Japanese data on perioperative and postoperative outcomes of patients who underwent salvage surgery after EGFR or ALK-TKI during 2010-2015. The primary endpoint was a 3-year overall survival (OS) rate and secondary endpoints were the rate of adverse events, perioperative mortality rate, 3-year recurrence-free survival (RFS) rate, and median survival time after salvage lung resection. Univariate and multivariate analyses were performed to identify independent prognostic factors of OS and RFS. RESULTS: Thirty-six patients were included (EGFR-TKI: 33, ALK-TKI: 3). The 3-year OS and RFS after the surgery were 75.1 % (95 % confidence interval [CI] 55.9-86.9 %) and 22.2 % (95 % CI 8.6-39.7 %), respectively. Of clinicopathological factors, the progression of disease while on TKI and preoperative carcinoembryonic antigen (CEA) levels (≥5 ng/mL) were shown to be worse independent prognosticators of OS (hazard ratio [HR] 9.38, 95 % CI 1.57-55.88, P = .014; HR 4.84, 95 % CI 1.62-14.46, P = .005, respectively). Older age at initial treatment (≥70 years) and advanced pathological T stage (T2-T4) were the worse prognosticators for RFS (HR 12.58, 95 % CI 2.51-62.97, P = .002; HR 3.06, 95 % CI 1.04-9.03, P = .043, respectively). Grade 3 adverse events occurred in 5.6 % (2/36) patients, but no deaths were reported within 90 days after surgery. CONCLUSION: Our study showed that salvage surgery after TKI treatment was safe and feasible and may contribute to prolonged OS time by reducing the local tumor burden.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Anciano , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/cirugía , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/cirugía , Mutación , Inhibidores de Proteínas Quinasas/efectos adversos , Estudios Retrospectivos
20.
Ann Thorac Surg ; 112(3): 862-873, 2021 09.
Artículo en Inglés | MEDLINE | ID: mdl-33248992

RESUMEN

BACKGROUND: The aim of this study was to describe the characteristics and outcomes of patients with non-small cell lung cancer undergoing salvage surgery after chemoradiotherapy, conventional external beam, stereotactic body radiotherapy, and ion beam radiotherapy. METHODS: We retrospectively evaluated patients who underwent salvage surgery between 2010 and 2016. Data on perioperative morbidity and mortality and patient outcomes were analyzed. RESULTS: In total, 156 patients were included; of those, 110 were categorized into category 1, chemoradiotherapy or conventional external beam; and 46 into category 2, stereotactic body radiotherapy or ion beam radiotherapy. Three-year overall survival (OS) and recurrence-free survival (RFS) in category 1 were 67.3% and 49.8%, respectively. In category 1, pathological nodal stage was an independent prognosticator of both OS (hazard ratio [HR] = 3.53, 95% confidence interval [CI], 1.05-11.83) and RFS (HR = 4.32, 95% CI, 1.32-14.14). In category 2, 3-year OS and RFS were 57.7% and 46.4%, respectively. Age 70 years and greater at initial treatment was the only independent prognosticator of OS (HR = 5.61; 95% CI, 1.44-21.87), whereas age at initial treatment (HR = 6.13; 95% CI, 1.38-27.12) and pathological nodal metastasis (HR = 3.84; 95% CI, 1.40-10.57) were independent prognosticators for RFS. Overall 30- and 90-day mortality were 0% and 0.9% in category 1 and 0% and 4.3% in category 2, respectively. CONCLUSIONS: Patients who undergo salvage surgery can have reasonable outcomes, and salvage surgery can be considered in selected patients.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/cirugía , Neoplasias Pulmonares/cirugía , Terapia Recuperativa , Anciano , Anciano de 80 o más Años , Carcinoma de Pulmón de Células no Pequeñas/radioterapia , Femenino , Humanos , Neoplasias Pulmonares/radioterapia , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Resultado del Tratamiento
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