En Bloc Resection of a Primary Tumor and Lymph Nodes in Non-Small-Cell Lung Cancer.

PURPOSE: We established a novel surgical procedure for resectable non-small-cell lung cancer (NSCLC), which involves resection of the affected lobe and regional lymph nodes without separation, namely en bloc surgery. We introduced the technical details and early and late outcomes by comparing them with those of conventional surgery. METHODS: We retrospectively analyzed patients who underwent lobectomy with hilar and mediastinal lymph node dissection for stages I-III NSCLC. A propensity score-matched analysis was performed based on demographic variables. RESULTS: Propensity score-matching yielded 317 pairs. En bloc surgery was not associated with a longer operation time, a higher amount of intraoperative bleeding, or a higher frequency of postoperative complications. The number of resected lymph nodes (P = 0.277) and frequency of N upstaging (P = 0.587) did not differ between the groups. However, en bloc surgery was associated with higher overall survival in comparison to conventional surgery (P = 0.012). According to a stratification analysis, the survival advantage of en bloc surgery over conventional surgery was remarkable in pathological N-positive disease (P = 0.005), whereas it disappeared in pathological N-negative disease (P = 0.147). CONCLUSION: En bloc surgery is feasible and can be performed in patients with possible N-positive NSCLC.

Successful Treatment with Osimertinib Based on Therapeutic Drug Monitoring in a Hemodialysis Patient with Non-Small Cell Lung Cancer: A Case Report.

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.

Approach to Functions of BHLHE41/DEC2 in Non-Small Lung Cancer Development.

The circadian rhythm-related genes BHLHE40/DEC1 and BHLHE41/DEC2 have various functions under different cell and tissue conditions. BHLHE41/DEC2 has been reported to be both a cancer-suppressive and an oncogenic gene during cancer development. The effects of BHLHE41/DEC2 on differentiation have been examined using Bhlhe41/Dec2 knockout mice and/or in vitro differentiation models, and research has been conducted using genetic analysis of tumor cells, in vitro analysis of cancer cell lines, and immunohistochemical studies of the clinical samples. We summarize some of these studies, detail several problems, and consider possible reasons for contradictory results and the needs for further research.

Clinical Significance of Nodal DCsign Expression in Non-small-cell Lung Cancer Patients.

BACKGROUND/AIM: Dendritic cells (DCs) are difficult to evaluate in lung regional lymph nodes because of region-specific structures, such as abundant trabeculae connecting the medullary and subcapsular sinuses, the latter of which contains few anthracotic macrophages. Therefore, DC-specific intercellular adhesion molecule-3-grabbing non-integrin (DCsign)-positive DCs and CD68-positive macrophages are unlikely to show a typical distribution. The present study therefore explored quantitative factors connecting the nodal DC morphology to the patient outcome. MATERIALS AND METHODS: Lymph nodes from 34 non-small-cell lung cancer patients who underwent complete resection were used for immunohistochemical assessments of DCsign and CD68 and terminal deoxynucleotidyl transferase dUTP nick-end labeling. Preoperative patient blood samples were used for the quantitative evaluation of monocytes. RESULTS: The nodal DCs showed a complementary distribution with macrophages, thus few DCs were seen in clusters of macrophages. DCs often presented as a mesh-like rosette that was solitary or connected to a DC cluster. DCs disappeared, and some macrophages were apoptotic when surrounded by cancer cells that have metastasized to lymph nodes. The proportional area of a DC cluster was significantly associated with the histological differentiation of cancer (p=0.013), with a higher ratio tending to lead to a better overall survival (p=0.059), and significantly so in adenocarcinoma (p=0.007). The rosette number was significantly correlated with the smoking index and blood monocyte number (p=0.013 and p=0.005, respectively). CONCLUSION: The nodal DC morphology appears useful as a prognostic factor and may lead to a new phase of clinicopathological studies of solid cancers.

Localization of macrophages and dendritic cells in human thoracic lymph nodes: An immunohistochemical study using surgically obtained specimens.

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.

Left atrial CT volume and CHA2DS2-VASc score predict early pulmonary vein stump thrombus after left upper lobectomy.

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.

Human lymph node degeneration in the thoracic region: A morphometric and immunohistochemical analysis using surgically obtained specimens.

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.

A case of ectopic cervical thymoma with myasthenia gravis mimicking a parathyroid tumour.

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.

Clinical Impact of a Pharmacist-Driven Prospective Audit with Intervention and Feedback on the Treatment of Patients with Bloodstream Infection.

Evidence for the utility of pharmacist-driven antimicrobial stewardship programs remains limited. This study aimed to evaluate the usefulness of our institutional pharmacist-driven prospective audit with intervention and feedback (PAF) on the treatment of patients with bloodstream infections (BSIs). The effect of pharmacist-driven PAF was estimated using an interrupted time series analysis with a quasi-experimental design. The proportion of de-escalation during BSI treatment increased by 44% after the implementation of pharmacist-driven PAF (95% CI: 30−58, p < 0.01). The number of days of therapy decreased by 16 per 100 patient days for carbapenem (95% CI: −28 to −3.5, p = 0.012) and by 15 per 100 patient days for tazobactam/piperacillin (95% CI: −26 to −4.9, p < 0.01). Moreover, the proportion of inappropriate treatment in empirical and definitive therapy was significantly reduced after the implementation of pharmacist-driven PAF. Although 30-day mortality did not change, compliance with evidenced-based bundles in the BSI of Staphylococcus aureus significantly increased (p < 0.01). In conclusion, our pharmacist-driven PAF increased the proportion of de-escalation and decreased the use of broad-spectrum antibiotics, as well as the proportion of inappropriate treatment in patients with BSI. This indicates that pharmacist-driven PAF is useful in improving the quality of antimicrobial treatment and reducing broad-spectrum antimicrobial use in the management of patients with BSI.

A case of schwannoma at the origin of the right recurrent laryngeal nerve resected under uniportal video-assisted thoracic surgery.

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.

Clinical significance of ALKBH4 expression in non-small cell lung cancer.

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.

First reported case of Lachnoanaerobaculum gingivalis bacteremia in an acute myeloid leukemia patient with oral mucositis during high dose chemotherapy.

CASE DESCRIPTION: Lachnoanaerobaculum gingivalis is an obligate anaerobe identified in a human dental plaque in 2019. Here, we report the first case of L. gingivalis bacteremia in a patient with oral mucositis during chemotherapy. L. gingivalis was confirmed by 16S rRNA gene analysis but not by MALDI-TOF-MS. CONCLUSION: During chemotherapy in patients with oral mucositis, we should consider the possibility of L. gingivalis bacteremia.

Intraoperative cone-beam computed tomography to secure the surgical margin in pulmonary wedge resection for indistinct intrapulmonary lesions.

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.

Effects of immune checkpoint inhibitor therapy resumption in patients with malignant tumors after moderate-to-severe immune-related adverse events.

BACKGROUND AND AIMS: Immune checkpoint inhibitors (ICIs) are used to treat several cancers, but they sometimes induce immune-related adverse events (irAEs). Patients with irAEs often have improved antitumor responses, but discontinuation of ICIs after irAEs is considered necessary. Resuming the use of ICIs after irAEs is preferable, but few studies have investigated the safety of ICI resumption after irAEs. Therefore, we evaluated the factors associated with the recurrence of irAEs after ICI resumption to investigate the safety of this approach. METHODS: In this observational study, we enrolled patients treated with ICIs from September 2014 to March 2020 at our institution. Patient characteristics, ICIs, grades of irAEs, ICI discontinuation or resumption rates, and recurrence rates of irAEs after ICI therapy were analysed. RESULTS: Two-hundred eighty-seven patients were included in the present study, and 76 patients experienced grade 2 or higher irAEs. Forty-two patients underwent ICI resumption after recovering from irAEs, and 13 of them had a recurrence of irAEs. Among those 13 patients, six had a recurrence of the same irAE, and seven experienced other irAEs. Ten of the 13 patients had grade ≥2 irAEs, and none had fatal irAEs. In the grade 2 or higher irAE group, more patients had irAEs associated with multiple organs and of initial grade ≥2 than those in the grade 1 and no recurrent irAEs group. CONCLUSIONS: Patients with initial multisystemic irAEs and irAEs of grade ≥2 were more likely to experience relapse or develop new grade ≥2 irAEs after ICI resumption.

The efficacy of 18F-FDG-PET-based radiomic and deep-learning features using a machine-learning approach to predict the pathological risk subtypes of thymic epithelial tumors.

OBJECTIVE: To examine whether the machine-learning approach using 18-fludeoxyglucose positron emission tomography (18F-FDG-PET)-based radiomic and deep-learning features is useful for predicting the pathological risk subtypes of thymic epithelial tumors (TETs). METHODS: This retrospective study included 79 TET [27 low-risk thymomas (types A, AB and B1), 31 high-risk thymomas (types B2 and B3) and 21 thymic carcinomas] patients who underwent pre-therapeutic 18F-FDG-PET/CT. High-risk TETs (high-risk thymomas and thymic carcinomas) were 52 patients. The 107 PET-based radiomic features, including SUV-related parameters [maximum SUV (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG)] and 1024 deep-learning features extracted from the convolutional neural network were used to predict the pathological risk subtypes of TETs using six different machine-learning algorithms. The area under the curves (AUCs) were calculated to compare the predictive performances. RESULTS: SUV-related parameters yielded the following AUCs for predicting thymic carcinomas: SUVmax 0.713, MTV 0.442, and TLG 0.479 or high-risk TETs: SUVmax 0.673, MTV 0.533, and TLG 0.539. The best-performing algorithm was the logistic regression model for predicting thymic carcinomas (AUC 0.900, accuracy 81.0%), and the random forest (RF) model for high-risk TETs (AUC 0.744, accuracy 72.2%). The AUC was significantly higher in the logistic regression model than three SUV-related parameters for predicting thymic carcinomas, and in the RF model than MTV and TLG for predicting high-risk TETs (each; p < 0.05). CONCLUSION: 18F-FDG-PET-based radiomic analysis using a machine-learning approach may be useful for predicting the pathological risk subtypes of TETs. ADVANCES IN KNOWLEDGE: Machine-learning approach using 18F-FDG-PET-based radiomic features has the potential to predict the pathological risk subtypes of TETs.

Hemodynamic features underlying pulmonary vein stump thrombus formation after left upper lobectomy: four-dimensional flow magnetic resonance imaging study.

BACKGROUND: We previously reported that to-and-fro blood movement near the pulmonary vein stump was particularly prominent after left upper lobectomy compared with other lobectomy, which may be the cause of the high susceptibility of pulmonary vein thrombus after left upper lobectomy. The aim of the present study was to compare the hemodynamics in patients who developed pulmonary vein thrombus after left upper lobectomy with those in patients who did not develop pulmonary vein thrombus using four-dimensional flow magnetic resonance imaging (4D MRI). METHODS: This was a retrospective evaluation of a prospectively collected clinical and radiological database of 37 patients who underwent 4D MRI 7 days after left upper lobectomy for lung cancer (n=37). We obtained two parameters by 4D MRI: the grade of to-and-fro blood movement and the flow energy loss around the pulmonary vein stump. The length of the pulmonary vein stump, a known risk factor for pulmonary vein thrombus, was also measured. RESULTS: According to a scatterplot of the grade of to-and-fro blood movement versus the flow energy loss, patients with pulmonary vein thrombus (n=15) were concentrated in an area which appears to be a 'dangerous' hemodynamic condition. There were few patients without pulmonary vein thrombus in this 'dangerous' area, except for one who unfortunately developed delayed pulmonary vein thrombus and cerebral infarction. We proposed a formula using the 4D MRI-derived parameters based on a stepwise multiple regression analysis that was more closely associated with the development of pulmonary vein thrombus than the length of the pulmonary vein stump (area under the receiver operating characteristics curve: 0.918 vs. 0.705, P=0.0500). CONCLUSIONS: We proposed the existence of a 'dangerous' hemodynamic condition responsible for pulmonary vein thrombus formation. 4D MRI before the development of pulmonary vein thrombus may help identify patients requiring preventive therapy against pulmonary vein thrombus and subsequent thromboembolic complications.

Intraoperative computed tomography of a resected lung inflated with air to verify safety surgical margin.

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.

Altered lymphatic structure and function in pleural anthracosis: negative role in skip N2 metastasis.

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.