The distribution of parenchyma, follicles, and lymphocyte subsets in thymus of patients with myasthenia gravis, with special reference to remission after thymectomy

ObjectiveWe sought to examine the distribution of parenchyma, follicles, and lymphocyte subsets in the thymus of patients with myasthenia gravis and to identify determinants of remission after thymectomy.MethodsSixty patients with myasthenia gravis who underwent thymectomy were examined. The thymus was divided into upper, middle, and lower parts. The upper part was defined as the superior horn, the lower part as the inferior horn, and the middle part as tissue located between the 2 horns. The percentage of parenchyma was measured morphometrically. The degree of follicular hyperplasia was classified into 5 grades. The densities of CD3+, CD4+, and CD8+ lymphocytes were classified into 5 grades. The remission of myasthenia gravis after thymectomy was examined with those variables in each part of the thymus.ResultsThe middle part had the highest percentage of parenchyma, the highest grade of follicular hyperplasia, and the highest density of CD3+, CD4+, and CD8+ lymphocytes among the 3 parts (P < .001-.05). The grades of follicular hyperplasia in the middle and lower parts were significantly higher in patients with improvement of myasthenia gravis than in those without (P < .05). The densities of CD3+, CD4+, and CD8+ lymphocytes in the cortex of the middle part were significantly higher in patients with improvement than in those without improvement (P < .01-.05).ConclusionsThe thymus has a heterogeneous distribution of parenchyma, follicles, and lymphocyte subsets. The middle part had the largest parenchyma, the highest grade of follicular hyperplasia, and the highest densities of CD3+, CD4+, and CD8+ lymphocytes among the 3 parts of the thymus. The grade of follicular hyperplasia and the density of these lymphocyte subsets are predictive of improvement in myasthenia gravis after thymectomy

Combined subsegmentectomy: postoperative pulmonary function compared to multiple segmental resection

<p>Abstract</p> <p>Background</p> <p>For small peripheral c-T1N0M0 non-small cell lung cancers involving multiple segments, we have conducted a resection of subsegments belonging to different segments, i.e. combined subsegmentectomy (CSS), to avoid resection of multiple segments or lobectomy. Tumor size, location of tumor, and forced expiratory volume in 1 second (FEV₁) of each preserved lobe were compared among the CSS, resection of single segment, and that of multiple segments.</p> <p>Methods</p> <p>FEV₁of each preserved lobe were examined in 17 patients who underwent CSS, 56 who underwent resection of single segment, and 41 who underwent resection of multiple segments, by measuring pulmonary function and lung-perfusion single-photon-emission computed tomography and computed tomography before and after surgery.</p> <p>Results</p> <p>Tumor size in the CSS was significantly smaller than that in the resection of multiple segments (1.4 ± 0.5 vs. 2.0 ± 0.8 cm, p = 0.002). Tumors in the CSS were located in the right upper lobe more frequently than those in the resection of multiple segments (53% vs. 5%, p < 0.001). Postoperative of FEV₁of each lobe after the CSS was higher than that after the resection of multiple segments (0.3 ± 0.2 vs. 0.2 ± 0.2 l, p = 0.07). Mean FEV₁of each preserved lobe per subsegment after CSS was significantly higher than that after resection of multiple segments (0.05 ± 0.03 vs. 0.03 ± 0.02 l, p = 0.02). There was no significant difference of these factors between the CSS and resection of single segment.</p> <p>Conclusions</p> <p>The CSS is effective for preserving pulmonary function of each lobe, especially for small sized lung cancer involving multiple segments in the right upper lobe, which has fewer segments than other lobes.</p

Comparison of postoperative pulmonary function and air leakage between pleural closure vs. mesh-cover for intersegmental plane in segmentectomy

<p>Abstract</p> <p>Background</p> <p>To prevent postoperative air leakage after lung segmentectomy, we used two methods for the intersegmental plane: closing it by suturing the pleural edge (pleural closure), or opening it with coverage using polyglycolic acid mesh and fibrin glue (mesh-cover). The preserved forced expiratory volume in one second (FEV₁) of each lobe and the postoperative air leakage were compared between the two groups.</p> <p>Methods</p> <p>For 61 patients who underwent pleural closure and 36 patients who underwent mesh-cover, FEV₁of the lobe before and after segmentectomy was measured using lung-perfusion single-photon-emission computed tomography and CT (SPECT/CT). The groups' results were compared, revealing differences of the preserved FEV₁of the lobe for several segmentectomy procedures and postoperative duration of chest tube drainage.</p> <p>Results</p> <p>Although left upper division segmentectomy showed higher preserved FEV₁of the lobe in the mesh-cover group than in the pleural closure one (<it>p </it>= 0.06), the other segmentectomy procedures showed no differences between the groups. The durations of postoperative chest drainage in the two groups (2.0 ± 2.5 vs. 2.3 ± 2.2 days) were not different.</p> <p>Conclusions</p> <p>Mesh-cover preserved the pulmonary function of remaining segments better than the pleural closure method in left upper division segmentectomy, although no superiority was found in the other segmentectomy procedures. However, the data include no results obtained using a stapler, which cuts the segment without recognizing even the intersegmental plane and the intersegmental vein. Mesh-cover prevented postoperative air leakage as well as the pleural closure method did.</p

Epidermal Growth Factor Receptor Mutations in Multicentric Lung Adenocarcinomas and Atypical Adenomatous Hyperplasias

BackgroundThe mechanisms of generation and progression of multicentric lung adenocarcinoma (AD), bronchioloalveolar carcinoma (BAC), and atypical adenomatous hyperplasia (AAH) in the peripheral lung is not well known. In this study, we analyzed epidermal growth factor receptor (EGFR) mutations in the cases of multicentric AD, BAC, and AAH to reveal the role of EGFR mutation in their generations and progressions.MethodNinety-seven AAH, BAC, or AD lesions less than 3 cm in size in 26 patients were surgically resected. Of these, EGFR mutations of the nodules with the highest and the second highest grade of histologic malignancy were examined in each patient by using the peptide nucleic acid-locked nucleic acid polymerase chain reaction (PNA-LNA PCR) clamp method.ResultsEGFR mutations could be examined in 48 nodules in the 26 patients. The EGFR mutations were found more frequently in lesions with higher histologic malignancy, ie, 9 of 10 ADs (90%), 16 of 28 BACs (57%), and one of 10 AAHs (10%). In 22 patients who could be examined of EGFR mutations for the two lesions in each patient, only two patients (9%) had the same mutation patterns between the two lesions, whereas 15 patients (68%) had the different statuses and the remaining five (23%) had no mutations.ConclusionOur data demonstrated that EGFR mutations seem to contribute to the acquisition of malignant potential in the AAH-AD sequence and occur independently in each lesion and in the cases of multicentric AD, BAC, and AAH

NUF2 Expression in Cancer Tissues and Lymph Nodes Suggests Post-Surgery Recurrence of Non-Small Cell Lung Cancer

In non-small cell lung cancer (NSCLC) cases, detecting potential lymph node metastases is essential to determine the indications for sublobar resection or adjuvant therapy. NUF2 is a tumor-specific antigen that is highly expressed in lung cancer tissues. However, the significance of analyzing NUF2 expression in dissected lymph nodes has not yet been studied. Thus, we investigated the association between NUF2 expression in lung cancer tissues and dissected lymph nodes and early recurrence of NSCLC to determine its usefulness as a marker of lymph node micrometastasis. This retrospective study quantified NUF2 expression in the cancer tissues of 88 patients with NSCLC who underwent complete resection using real-time polymerase chain reaction and investigated its relationship with clinicopathological features and prognosis. We also quantified NUF2 RNA expression in mediastinal lymph nodes from 255 patients with pN0 NSCLC who underwent complete resection with lymph node dissection and analyzed its association with prognosis. NUF2 expression in primary tumors was correlated with lymph node metastasis and unfavorable outcomes in terms of poor recurrence-free and cancer-specific survival. In N0 NSCLC cases, high NUF2 expression in mediastinal lymph nodes indicated poor prognosis, especially in lymph node recurrence. NUF2 emerges as a promising marker for predicting lymph node metastatic recurrence, offering potential utility in guiding post-surgical adjuvant therapy for lung cancer or assisting in intraoperative decisions for sublobar resection

Clinical Implications and Molecular Characterization of Drebrin-Positive, Tumor-Infiltrating Exhausted T Cells in Lung Cancer

T cells express an actin-binding protein, drebrin, which is recruited to the contact site between the T cells and antigen-presenting cells during the formation of immunological synapses. However, little is known about the clinical implications of drebrin-expressing, tumor-infiltrating lymphocytes (TILs). To address this issue, we evaluated 34 surgical specimens of pathological stage I&ndash;IIIA squamous cell lung cancer. The immune context of primary tumors was investigated using fluorescent multiplex immunohistochemistry. The high-speed scanning of whole-slide images was performed, and the tissue localization of TILs in the tumor cell nest and surrounding stroma was automatically profiled and quantified. Drebrin-expressing T cells were characterized using drebrin+ T cells induced in vitro and publicly available single-cell RNA sequence (scRNA-seq) database. Survival analysis using the propensity scores revealed that a high infiltration of drebrin+ TILs within the tumor cell nest was independently associated with short relapse-free survival and overall survival. Drebrin+ T cells induced in vitro co-expressed multiple exhaustion-associated molecules. The scRNA-seq analyses confirmed that the exhausted tumor-infiltrating CD8+ T cells specifically expressed drebrin. Our study suggests that drebrin-expressing T cells present an exhausted phenotype and that tumor-infiltrating drebrin+ T cells affect clinical outcomes in patients with resectable squamous cell lung cancer

Synchronous Multiple Lung Adenocarcinomas: Estrogen Concentration in Peripheral Lung

<div><p>Background</p><p>The detection rate of synchronous multiple lung adenocarcinomas (SMLA), which display multiple ground glass opacity nodules in the peripheral lung, is increasing due to advances in high resolution computed tomography. The backgrounds of multicentric development of adenocarcinoma are unknown. In this study, we quantitated estrogen concentration in the peripheral lungs of postmenopausal female patients with SMLA.</p><p>Methods</p><p>The tissue concentration of estrogens (estrone [E1] and estdadiol [E2]) in the noncancerous peripheral lung were measured with liquid chromatography/electrospray tandem mass spectrometry in postmenopausal female patients with lung adenocarcinoma. The expression levels of <i>CYP19A1</i> in the normal lung were also quantitated with real-time PCR. Thirty patients with SMLA and 79 cases of control patients with single lung adenocarcinoma were analyzed.</p><p>Results</p><p>The concentrations of E1 and E2 in the noncancerous tissue were significantly higher in SMLA cases than control cases (P = 0.004 and P = 0.02, respectively). The minor allele (A) of single nucleotide polymorphism rs3764221 were significantly associated with higher concentration of E1 and E2 (P = 0.002 and P = 0.01, respectively) and higher CYP19A1 mRNA expression (P = 0.03).</p><p>Conclusion</p><p>The tissue estrogen concentration of peripheral lung was significantly higher in SMLA than control cases. The high concentration of estrogen may be one of the causes of multicentric development of peripheral lung adenocarcinomas.</p></div