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PURPOSE: Immune checkpoint inhibitors (ICI) ushered in a new era for the treatment of non-small cell lung cancer (NSCLC). However, they carry the risk of immune-related adverse events (irAEs). Recently, various studies have been conducted on the predictive factors for irAEs, but there are no reports focusing only on ICI plus platinum agents. The present study aimed to identify the risk factors for irAEs due to ICI combined with platinum-based induction immunochemotherapy in NSCLC patients, focusing only on the period of combined therapy and excluding the period of ICI maintenance therapy. METHODS: This retrospective study included 315 NSCLC patients who started ICI combined with platinum-based chemotherapy treatment at 14 hospitals between December 2018 and March 2021. A logistic regression analysis was used to explore the predictive factors. RESULTS: Fifty patients (15.9%) experienced irAEs. A multivariate analysis revealed that squamous cell carcinoma (P = 0.021; odds ratio [OR]: 2.30; 95% confidence interval [Cl]: 1.14-4.65), anti-programmed death 1 antibody (anti-PD-1) plus anti-cytotoxic T-lymphocyte antigen-4 antibody (anti-CTLA-4) regimens (P < 0.01; OR: 22.10; 95% Cl: 5.60-87.20), and neutrophil-to-lymphocyte rate (NLR) < 3 (P < 0.01; OR: 2.91; 95% Cl: 1.35-6.27) were independent predictive factors for irAEs occurrence. CONCLUSION: Squamous cell carcinoma, anti-PD-1 plus anti-CTLA-4 regimens, and NLR < 3 may be predictive factors for the occurrence of irAEs due to induction immunochemotherapy in patients with NSCLC. By focusing on the potential risk of irAEs in patients with these factors, irAEs can be appropriately managed from an early stage.
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Carcinoma Pulmonar de Células não Pequenas , Carcinoma de Células Escamosas , Neoplasias Pulmonares , Humanos , Estudos Retrospectivos , Inibidores de Checkpoint Imunológico/efeitos adversos , Neoplasias Pulmonares/tratamento farmacológico , Receptor de Morte Celular Programada 1 , Fatores de Risco , Quimioterapia Combinada , Carcinoma de Células Escamosas/tratamento farmacológicoRESUMO
Both dendritic cells (DCs) and macrophages are bone marrow-derived cells that perform antigen presentation. The distribution of DCs and CD68-positive macrophages were immunohistochemically examined in 103 thoracic nodes obtained from 23 lung cancer patients (50-84 years old) without metastasis. Among three antibodies tested initially-CD209/DCsign, fascin, and CD83-DCsign was chosen as the DC marker. For comparison, 137 nodes from 12 patients with cancer metastasis were also examined histologically. In patients without metastasis, DCs were found as (1) clusters along the subcapsular sinus and in a border area between the medullary sinus and cortex (mean sectional area of multiple nodes at one site, 8.4%) and, (2) rosette-like structures in the cortex (mean number in multiple nodes at one site, 20.5). Notably, DC clusters and rosettes contained no or few macrophages and were surrounded by smooth muscle actin (SMA)-positive, endothelium-like cells. The subcapsular linear cluster corresponded to 5%-85% (mean, 34.0%) of the nodal circumferential length and was shorter in older patients (p = 0.009). DC rosettes, solitary, or communicating with a cluster, were usually connected to a paracortical lymph sinus. Few differences were found between nodes with or without metastasis, but DC cluster sometimes contained abundant macrophages in cancer metastasis patients. The subcapsular DC cluster is not known in the rodent model, in which the subcapsular sinus is filled with macrophages. This quite different, even complementary, distribution suggests no, or less, cooperation between DCs and macrophages in humans.
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Vasos Linfáticos , Macrófagos , Humanos , Idoso , Pessoa de Meia-Idade , Idoso de 80 Anos ou mais , Linfonodos , Células DendríticasRESUMO
PURPOSE: Pulmonary lymphatic fluid predominately flows along the bronchi. However, there are reports suggesting that an alternative lymphatic pathway exist, which may result in skip metastases. The aim of this study was to evaluate the subpleural lymph flow in vivo using indocyanine green (ICG) fluorescence. METHODS: One hundred cases were enrolled. ICG was injected into the macroscopically healthy subpleural space. Intraoperative fluorescence images were then observed in real time. RESULTS: ICG fluorescence was observed moving through subpleural channels in 58/100 cases. ICG flowed into adjacent lobes over interlobar lines in 18 cases and flowed from the visceral pleura directly into the mediastinum in 5 cases. The frequency of mediastinal detection without hilar lymph node detection was significantly higher in the left lung compared to the right (p < 0.05). The subpleural lymph flow detection rates were significantly lower in patients with smoking pack-years ≥ 40 than those with < 40 (p < 0.05). CONCLUSIONS: The flow of lymphatic fluid directly into the mediastinum suggests one mechanism of skip metastasis. In addition, the reduction of the subpleural lymph flows in smokers with ≥ 40 pack-years suggests that smoking might modify lymph flow patterns. These findings may assist in selecting the optimal therapy for patients with possible skip metastasis.
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Corantes Fluorescentes , Verde de Indocianina , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologia , Linfa/diagnóstico por imagem , Vasos Linfáticos/diagnóstico por imagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Brônquios , Feminino , Humanos , Pulmão , Neoplasias Pulmonares/cirurgia , Metástase Linfática , Vasos Linfáticos/patologia , Masculino , Mediastino , Pessoa de Meia-Idade , PneumonectomiaRESUMO
We report a case of iatrogenic esophageal injury treated with a covered expandable metallic stent after thoracoscopic chest drainage. A 70-year-old man who had stricture of the esophagus after endoscopic submucosal dissection underwent balloon dilation. Chest computed tomography revealed esophageal rupture. Initially, continuous intra-esophageal drainage was carried out, however, due to the development of mediastinitis with enlarged abscess around the descending aorta and the left pneumothorax, thoracoscopic chest drainage was performed. Since direct closure was thought to be in appropriate, an intra-esophageal approach was chosen and a covered expandable metallic stent was mounted under fluorography on the next day. After the treatment, the patient was able to eat, and was able to discharge 42 days later. Intra-esophageal covered expandable metallic stent can be an alternative treatment for esophageal rupture.
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Esôfago/lesões , Metais , Ruptura/terapia , Stents , Idoso , Dilatação/efeitos adversos , Drenagem , Mucosa Esofágica/cirurgia , Esôfago/diagnóstico por imagem , Humanos , Doença Iatrogênica , Masculino , Radiografia Torácica , Ruptura/diagnóstico por imagem , Ruptura/etiologia , Toracoscopia , Tomografia Computadorizada por Raios X , Resultado do TratamentoRESUMO
We reported a case of metastatic lung tumor, which was suspected as being a primary lung cancer because of its accompanying lesion mimicking atypical adenomatous hyperplasia(AAH) based on intraoperative needle biopsy findings. AAH is a preinvasive lesion or marginal lesion of primary lung cancer that is not accompanied by metastatic tumor. However, it needs to be distinguished pathologically from secondary changes of inflammation or fibrosis. In our case, the needle biopsy revealed AAH-like pathological findings, which indicates a primary lung cancer, and the standard lobectomy with lymph node dissection was performed, however, the final diagnosis turned out to be metastatic tumor. The rapidly enlarging tumor led to surrounding obstructive pneumonitis, which may have caused pathological changes mimicking AAH findings. In the case of obstructive pneumonitis, we must be careful to diagnose AAH, in addition to decisions about the surgical procedure especially when based on frozen section diagnosis.
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Diagnóstico Diferencial , Hiperplasia/diagnóstico , Neoplasias Pulmonares/patologia , Biópsia por Agulha , Feminino , Humanos , Hiperplasia/patologia , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/secundário , Neoplasias Pulmonares/cirurgia , Excisão de Linfonodo , Pessoa de Meia-Idade , Pneumonectomia , Neoplasias Retais/patologia , Tomografia Computadorizada por Raios XRESUMO
PURPOSE: Regardless of the devastating outcomes of pulmonary resection for metastases from gastric cancer, a handful of patients survive long after pulmonary metastasectomy. This study aimed to identify a good candidate for pulmonary resection for metastases from gastric cancer. METHODS: Between 2005 and 2023, 564 patients underwent pulmonary metastasectomy in our department, of which 12 patients underwent pulmonary resection for metastases from gastric cancer. Variables evaluated were the number and size of metastatic lesions, surgical procedure, disease-free interval (DFI), and the serum carcinoembryonic antigen at pulmonary metastasectomy. RESULTS: The DFI following gastrectomy ≤12.5 months group had a significantly worse overall survival (OS) than the other group (p = 0.005). A comparison between DFI following gastrectomy ≤12.5 months group and DFI following gastrectomy >12.5 months group showed a significant difference in serum carcinoembryonic antigen (CEA) value at pulmonary metastasectomy (p = 0.048). The serum CEA value at pulmonary metastasectomy >5.8 ng/ml group had a significantly worse OS than the other group (p = 0.001). CONCLUSION: Pulmonary metastasectomy can be indicated in some patients with metastasis from gastric cancer who have longer DFI from gastrectomy and lower serum CEA at pulmonary metastasectomy.
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Antígeno Carcinoembrionário , Gastrectomia , Neoplasias Pulmonares , Metastasectomia , Pneumonectomia , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/sangue , Neoplasias Pulmonares/secundário , Neoplasias Pulmonares/cirurgia , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/sangue , Metastasectomia/mortalidade , Metastasectomia/efeitos adversos , Masculino , Feminino , Pneumonectomia/mortalidade , Pneumonectomia/efeitos adversos , Pessoa de Meia-Idade , Gastrectomia/mortalidade , Gastrectomia/efeitos adversos , Antígeno Carcinoembrionário/sangue , Idoso , Fatores de Tempo , Resultado do Tratamento , Estudos Retrospectivos , Intervalo Livre de Doença , Fatores de Risco , Estimativa de Kaplan-Meier , Adulto , Biomarcadores Tumorais/sangue , Seleção de PacientesRESUMO
Pleurectomy/decortication for malignant pleural mesothelioma is a relatively recent surgical approach for which there is a dearth of information on complications, especially in the late postoperative period. A 70-year-old man was diagnosed with right epithelioid malignant pleural mesothelioma and underwent pleurectomy/decortication. Computed tomography at 6 months after surgery revealed nodules on the surface of the right lung. These nodules gradually increased in size and were diagnosed as recurrent disease. Immunotherapy was started, but treatment was discontinued a few days after the first course due to pneumonitis. Subsequent oral prednisolone therapy for about 2 months ameliorated pneumonitis, but fistulous pyothorax developed. During attempted transbronchial occlusion of the responsible bronchus, some spigots penetrated the empyema cavity. Open window thoracotomy was performed on the following day. This case suggests that if there is no change in diameter between the proximal and distal parts of the responsible bronchus, transbronchial occlusion should not be chosen.
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PURPOSE: Tegafur-uracil (UFT) is the standard postoperative adjuvant therapy for stage IB lung adenocarcinoma (LUAD) in Japan. This study aimed to determine whether UFT is effective in stage IB LUAD with and without epidermal growth factor receptor (EGFR) mutations. METHODS: This retrospective study included 169 patients with stage IB LUAD who underwent complete resection at our department between 2010 and 2021. We investigated the clinicopathological and prognostic impact of EGFR mutations as well as the postoperative use of UFT. RESULTS: EGFR mutation-positive cases tended to show a higher cumulative recurrence rate than EGFR mutation-negative cases (p = 0.081), while overall survival was comparable between the groups (p = 0.238). In the entire cohort, UFT administration was not an independent prognostic factor in the multivariate regression analysis (p = 0.112). According to a stratification analysis, UFT administration was independently associated with favorable overall survival (p = 0.031) in EGFR mutation-negative cases, while it was not associated with recurrence-free survival (p = 0.991) or overall survival (p = 0.398) in EGFR mutation-positive cases. CONCLUSION: UFT administration can improve the prognosis of EGFR mutation-negative LUAD but not EGFR mutation-positive LUAD. Thus, clinical trials of adjuvant-targeted therapy for EGFR mutation-positive stage IB LUAD should also be conducted in Japan.
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Adenocarcinoma de Pulmão , Adenocarcinoma , Neoplasias Pulmonares , Humanos , Tegafur/efeitos adversos , Estudos Retrospectivos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/cirurgia , Adenocarcinoma/patologia , Genes erbB-1 , Resultado do Tratamento , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/patologia , Prognóstico , Mutação , Receptores ErbB/genética , Estadiamento de Neoplasias , Quimioterapia AdjuvanteRESUMO
INTRODUCTION: Lung adenocarcinoma with a preoperatively elevated serum carcinoembryonic antigen (CEA) value has a relatively poor postoperative prognosis. Although surgical resection generally results in a reduction in the CEA value, the significance of the change in the CEA value on the prognostic outcome remains unclear. METHODS: Our study included 133 patients who underwent lobectomy with curative intent for lung adenocarcinoma representing a preoperative CEA value > 5.0. Statistical analysis was performed using a receiver operating characteristic analysis and a stepwise Cox proportional hazards analysis. RESULTS: Both the postoperative CEA value and postoperative-to-preoperative CEA ratio (CEA ratio) significantly affected the survival. Although the CEA ratio was not predictive of the survival in patients with postoperative CEA ≤ 6.2 ng/ml (n = 105), it was predictive in the remaining patients with postoperative CEA > 6.2 ng/ml (n = 28). Patients with postoperative CEA > 6.2 ng/ml and a CEA ratio ≥ 0.39 (n = 7) showed the worst survival outcome. According to the multivariate analysis, the CEA ratio and postoperative nodal status were significant predictors of the survival in overall patients. CONCLUSION: The CEA ratio may be a useful prognostic marker in patients who undergo lobectomy for lung adenocarcinoma and show postoperative CEA > 6.2 ng/ml. A high CEA ratio may indicate the presence of a subclinical residual tumor, which may lead to the development of subsequent recurrence.
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BACKGROUND: Post-pneumonectomy syndrome (PPS) is a rare but serious condition that can occur after pneumonectomy. It is characterized by a mediastinal shift towards the vacated hemithorax, which can potentially lead to respiratory failure. The management of PPS poses a clinical challenge, especially in the context of the limited availability of certain therapeutic devices due to regulatory restrictions in Japan. CASE PRESENTATION: A 36-year-old female with stage IB non-small cell lung cancer underwent left pneumonectomy. Approximately 2 years later, she developed dyspnea. After consulting with our hospital, subsequent imaging revealed an extreme mediastinal shift causing bronchial obstruction. Emergency thoracotomy and subsequent sulfur hexafluoride (SF6) injections were successfully used to manage her condition. Over the course of follow-up, the interval between SF6 injections was extended from 3 to 11 months, indicating an improvement in the intrathoracic condition. CONCLUSIONS: This case illustrates the efficacy of SF6 gas in treating PPS and in reducing the frequency of medical interventions. SF6 gas administration is safe and effective for the treatment of patients with PPS.
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The purpose of this study is to clarify the feasibility of left atrial (LA) volume measurement and CHA2DS2-VASc score for predicting the development of pulmonary vein (PV) stump thrombus after left upper lobectomy (LUL). The study population comprised 50 patients who underwent LUL for pulmonary lesions. All patients were evaluated for the development of PV stump thrombus at 7 days after LUL. LA volume was measured using preoperative CT and the CHA2DS2-VASc score was evaluated. LA volume and CHA2DS2-VASc score were compared between patients with and without the development of PV stump thrombus using the Mann-Whitney U test. Receiver-operating characteristic (ROC) curve analysis was performed to evaluate the accuracy of prediction of PV stump thrombus development. PV stump thrombus was detected in 17 (33.4%) of the 50 patients. LA volume was significantly greater in patients who developed PV stump thrombus than in those without thrombus (79.7 ± 19.4 vs. 66.6 ± 17.0 mL, p = 0.040). CHA2DS2-VASc score was significantly higher in patients with PV stump thrombosis than in those without thrombus (3.4 ± 1.5 vs. 2.5 ± 1.5, p = 0.039). Area under the ROC curve values for predicting PV stump thrombus were 0.679, 0.676, and 0.714 for LA volume, CHA2DS2-VASc score, and their combination, respectively. In conclusion, LA volume measured using preoperative CT and CHA2DS2-VASc score may help predict the development of PV stump thrombus after LUL.
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Fibrilação Atrial , Veias Pulmonares , Trombose , Trombose Venosa , Humanos , Fatores de Risco , Veias Pulmonares/diagnóstico por imagem , Veias Pulmonares/cirurgia , Medição de Risco , Trombose/diagnóstico por imagem , Trombose/etiologia , Trombose/epidemiologia , Tomografia Computadorizada por Raios X , Valor Preditivo dos TestesRESUMO
Although osimertinib is a key drug in the treatment of non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutation, the safety in hemodialysis patients has not been established. A 76-year-old man was diagnosed with NSCLC with EGFR deletion mutation in exon 19. After treatment failure with first- and second-generation EGFR tyrosine kinase inhibitors, a T790M mutation was revealed by liquid biopsy. Hemodialysis was started three times a week because chronic renal failure worsened during treatment. Although the subsequent administration of osimertinib (80 mg daily) resulted in a tumor shrinkage and a gradual increase in the plasma concentration of osimertinib, which resulted in grade 3 general fatigue, reducing the dosage of osimertinib decreased its plasma concentration, leading to an improvement in his adverse event. Subsequently, with by adjusting the dosage while periodically measuring the plasma concentration of osimertinib, a stable therapeutic effect was sustained over the long term with no symptoms. Periodic plasma concentration measurements may be indispensable for successful treatment with osimertinib in hemodialysis patients.
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Reports of cervical thymoma with myasthenia gravis are rare. In addition, 99mTc-MIBI (methoxyisobutylisonitrile:sestamibi) scintigraphy is a useful diagnostic examination for enlarged parathyroid tumours; however, there are a few reports of its accumulation in thymoma. Among them, there are no reports of cervical thymomas with 99mTc-MIBI accumulation complicated by myasthenia gravis. In this study, we performed surgery on a patient with preoperative myasthenic crisis accompanied by a cervical thymoma and a parathyroid tumour. Preoperatively, the cervical mass was determined to be a parathyroid tumour and was complicated by myasthenia gravis without thymic tumour. However, a pathological examination revealed that the cervical tumour with 99mTc-MIBI accumulation was a Type B2 thymoma, and a parathyroid tumour was identified in the vicinity. We report a very rare case in which symptoms improved with surgery.
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Lymph node degeneration was examined in 539 mediastinal and intrapulmonary nodes removed from 78 patients, aged 49-82 years, without cancer metastasis. Medullary sinus hyalinization observed in 36.2% of the hilar and 38.5% of the interlobar nodes. Early and smaller lesions were eosinophilic and factor VIII-positive, whereas advanced and large lesions contained a bulky mass of collagenous fiber bundles with few slender cells positive for smooth muscle actin (SMA) and factor VIII, as well as anthracotic macrophages. Subcapsular sinus hyalinization, observed in 4.3% of hilar nodes, was detected as a thick fibrous layer (over 0.2 mm) between the surface cortex and the thickened capsule. The fibrous layer contained SMA-positive slender cells, whereas the thickened capsule contained fibers positive for elastin and factor VIII. These hyalinization lesions occupied 3.6% and 0.8% of the sectional areas of hilar and lower paratracheal nodes, respectively. Areas of early and small cortical degeneration, surrounded by fibers positive for SMA and vimentin, did not contain lymphocytes and macrophages, but contained abundant small stromal cells. Silver staining suggested that advanced cortical degeneration was composed of collagen fibrils other than type I. Fatty tissues, seen in 47.8% of hilar nodes, often extended into and replaced medullary sinus tissue. Island-like remnants of medullary sinuses in areas of fatty degeneration contained various stromal cells positive for SMA, elastin, factor VIII and/or CD34. These degenerative morphologies, however, did not correlate with either age or smoking index. The present cortical degeneration usually seemed to follow hyalinization, but both were likely to occur independently.
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BACKGROUND: During sublobar resection for small, indistinct lung cancer, surgeons may be uncertain as to whether or not the target lesion has been resected and the surgical margin is sufficient. We herein report our procedure for confirming the success of sublobar resection without incising the resected specimen. METHODS: We reviewed our initial experience of 12 patients with intrapulmonary lesions (consolidation diameter ≤1 cm) who underwent thoracoscopic pulmonary wedge resection using autostapler. Six patients had primary adenocarcinoma showing part solid lesion, and remaining six patients had metastatic carcinoma showing purely solid lesion. Intraoperatively, the resected specimen was inflated with air and subjected to computed tomography (CT). The maximum tumor diameter and surgical margin length were measured intraoperatively on CT and postoperatively on formalin-fixed specimen. Surgical stump cytology was also done to verify surgical margin. RESULTS: According to the intraoperative CT, complete resection was confirmed in all patients. The intraoperative CT-based maximum tumor diameter closely correlated with the macroscopically measured one (r=0.971, P<0.0001). However, the tumor shrunk after formalin-fixation by 16.0% in patients with primary lung cancer (P<0.01), but not in patients with metastatic lung cancer. The intraoperative CT-based margin length closely correlated with the macroscopically measured one (r=0.984, P<0.0001). However, the margin shrunk after formalin-fixation in both patients with primary lung cancer and metastatic lung cancer, by 15.1% and 15.7%, respectively. Stump cytology was negative in all patients. Consequently, no recurrence was found during postoperative follow-up of 23 months (range, 14-31 months). CONCLUSIONS: Intraoperative CT is reliable for diagnosing the presence of a target lesion within the resected specimen as well as for estimating the surgical margin length in patients undergoing sublobar resection for intrapulmonary indistinct lesions.
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Mediastinal neurogenic tumours are mostly derived from sympathetic nerves and intercostal nerves, and vagus nerve-derived schwannomas are rare. We encountered a tumour originating from the origin of the recurrent laryngeal nerve that was accompanied by the azygos lobe, which made it difficult to approach; it was ultimately able to be removed via uniportal video-assisted thoracic surgery. This case involved a 63-year-old female patient. There were no particular symptoms, but an abnormal chest shadow was noted on an imaging examination. Chest imaging revealed a smooth-surfaced mass in the upper right mediastinum with the azygos lobe. A diagnosis of schwannoma was made by imaging, and the patient underwent resection via uniportal video-assisted thoracic surgery. The tumour, which originated from the origin of the right recurrent laryngeal nerve, was sharply removed without causing recurrent laryngeal nerve palsy.
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Objective: The objective of this study was to use cone-beam computed tomography (CBCT) for intraoperative imaging of a pulmonary wedge resection line that contributes to securing the required surgical margin in patients undergoing thoracoscopic surgery for indistinct intrapulmonary lesions. Methods: Data of 16 consecutive patients with potentially impalpable intrapulmonary lesions were retrospectively reviewed. Preoperatively, we simulated a rhomboidal cut line on the surface of a 3-dimensional lung model with reference to multiplanar reconstruction computed tomography images. Intraoperatively, we imaged the rhomboid on the real lung surface using trial and error adjustment with CBCT. Wedge resection was performed thoracoscopically by stapling along the outline of the rhomboid. Results: The mean consolidation diameter and mean distance between the tumor and the visceral pleura were 2 mm and 11 mm, respectively. In all cases, we only performed single CBCT scanning to localize the rhomboid on the real lung surface. The mean radiological distance between the approximate location and the correct location was 8 mm (range, 0-34 mm). Wedge resection was successful with a mean surgical margin of 11 mm (range, 7-16 mm), without conversion to anatomical resection or open conversion. This simulation was also helpful for planning port placement for the use of an autostapler. Conclusions: We established a novel procedure for imaging the cut line on the lung surface with intraoperative CBCT, which facilitated the performance of wedge resection with the required surgical margin in patients with potentially impalpable intrapulmonary small lesions. Our method might be beneficial for patients and surgeons because it can be applied without preoperative intervention.
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Rectal duplication cysts are extremely rare and account for only 4% of all gastrointestinal duplication cysts. They may become challenging for removal in the case of a large tumor in a narrow pelvis. Herein, we report a case of rectal duplication cysts excision via robotic-assisted laparoscopic surgery and its utility.
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OBJECTIVES: The present study investigated whether or not pleural anthracosis is associated with changes in the pleural lymphatic structures or function, which would interfere with nodal skip metastasis. METHODS: This study comprised 2 different case series. In the first series, we observed pleural lymphatic drainage using near-infrared fluorescent endoscopy by the subpleural injection of indocyanine green immediately after thoracotomy for lung cancer. We also performed a histological assessment of the pleura. In the second series, we reviewed the nodal metastatic pattern (skip or non-skip metastasis) in pathological N2 lung cancer involving the pleura. These findings were compared with the severity of pleural anthracosis, which was quantified by thoracoscopic vision and a software-based imaging analysis. RESULTS: In the first series (n = 42), pleural lymphatic drainage was not visualized in 19 (45%) patients who had relatively severe anthracosis, while it was visualized in the remaining 23 (55%) patients who had relatively minimal anthracosis. Histologically, severe anthracosis was associated with pleural thickening accompanied by a decreased incidence of straight-running lymphatic vessels and, in turn, an increased incidence of short lymphatic vessels, which was suggested to be the result of pleural remodelling. In the second series (n = 53), a skip metastatic pattern was found in 24 (45%) patients who predominantly had less-severe anthracosis, while a non-skip metastatic pattern was found in 29 (55%) patients who predominantly had severe anthracosis. CONCLUSIONS: Pleural anthracosis was associated with pathological changes in the pleural lymphatics and decreased pleural lymphatic drainage, thereby interfering with nodal skip metastasis.
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Antracose , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Vasos Linfáticos , Antracose/patologia , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Humanos , Verde de Indocianina , Neoplasias Pulmonares/cirurgia , Linfonodos/patologia , Metástase Linfática/patologia , Vasos Linfáticos/patologia , Estadiamento de Neoplasias , Prognóstico , Estudos RetrospectivosRESUMO
Background: Gene methylation is deeply involved in epigenetics and affects both the development and maintenance of homeostasis and carcinogenesis. ALKBH4 is a member of the AlkB homolog (ALKBH) family that controls demethylation of DNA and RNA. Methods: This study enrolled 160 patients with non-small cell lung cancer (NSCLC) who underwent complete resection. The expression of ALKBH4 in cancer tissue was evaluated by immunohistochemistry. The correlation among the expression of ALKBH4, clinicopathological factors, and prognostic outcome was evaluated. Results: In the NSCLC clinical samples, the expression of ALKBH4 was identified not only in cell membranes but also in the cytoplasm of cancer cells. In 140 of 160 cases, ALKBH4 was more highly expressed in the cancerous tissue than in the surrounding normal tissue. The proportion of cancer cells expressing ALKBH4 was higher in adenocarcinoma than in other histological types. In addition, the expression intensity of ALKBH4 in each cancer cell was also stronger in adenocarcinoma than in squamous cell carcinoma. The expression of ALKBH4 was not associated with clinicopathological factors, except for histological type. In adenocarcinoma, the recurrence-free survival (RFS) and overall survival (OS) rates were significantly lower in the ALKBH4-positive group than in the ALKBH4-negative group (P=0.008, 0.031, respectively). A multivariate logistic regression analysis indicated that the ALKBH4 expression was an independent prognostic factor for RFS (P=0.003) and OS (P=0.013). The expression of ALKBH4 was observed in all four patients with adenocarcinoma in situ. Conclusions: The ALKBH4 expression may be a useful predictor of the postoperative outcomes of lung adenocarcinoma (LUAD) patients.