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Background Extended sleeve lobectomy is a useful technique for avoiding pneumonectomy; however, it requires advanced surgical skills. Case presentation Herein, we report the case of a 67-year-old male, who presented with locally advanced lung adenocarcinoma in the left lower lobe and was scheduled to undergo extended sleeve lobectomy (left lower lobectomy + lingulectomy). In order to complete this operation safely, we practiced the procedure on fresh-frozen human cadavers 2 weeks before the surgery. The cadaveric tissue was soft, and the bronchi exhibited comparable fragility to those in the living body. During the actual surgery, the bronchoplasty procedure matched our experience with the cadaver model, and the patient’s postoperative course was uneventful. Conclusions Fresh-frozen human cadavers are useful for training surgeons in technically demanding procedures.

Background Micronodular thymic carcinoma with lymphoid hyperplasia is an extremely rare thymic tumor, exhibiting a variety of cell morphologies with mild to severe dysmorphism. Since few cases have been reported, the prognosis of this disease is unclear. Case presentation A 55-year-old woman was referred to our hospital with an anterior mediastinal tumor. She was incidentally detected with a tumor in a medical examination. We diagnosed the patient with thymic carcinoma or thymoma and performed surgery via median sternotomy. Histologically, tumor cells showed weakly acidic vesicles and bright nuclei, including small nucleoli. Most of the tumor cells were cluster of differentiation (CD)5-positive, CD3-negative, and terminal deoxynucleotidyl transferase (TdT)-negative. Conclusions Based on these histological findings, the resected specimen was diagnosed as micronodular thymic carcinoma with lymphoid hyperplasia. The patient’s postoperative course was uneventful, and no signs of recurrence were observed at 5 years after the surgery.

Background: Congenital hypothyroidism is often caused by genetic mutations that impair thyroid hormone (TH) production, resulting in growth and development defects. XB130 (actin filament associated protein 1 like 2) is an adaptor/scaffold protein that plays important roles in cell proliferation, migration, intracellular signal transduction, and tumorigenesis. It is highly expressed in thyrocytes, however, its function in the thyroid remains largely unexplored. Methods: Xb130(−/−) mice and their littermates were studied. Postnatal growth and growth hormone levels were measured, and responses to low or high-iodine diet, and levothyroxine treatment were examined. TH and thyrotropin in the serum and TH in the thyroid glands were quantified. Structure and function of thyrocytes in embryos and postnatal life were studied with histology, immunohistochemistry, immunofluorescence staining, Western blotting, and quantitative reverse transcription polymerase chain reaction. Results: Xb130(−/−) mice exhibited transient growth retardation postnatally, due to congenital hypothyroidism with reduced TH synthesis and secretion, which could be rescued by exogenous thyroxine supplementation. The thyroid glands of Xb130(−/−) mice displayed diminished thyroglobulin iodination and release at both embryonic and early postnatal stages. XB130 was found mainly on the apical membrane of thyroid follicles. Thyroid glands of embryonic and postnatal Xb130(−/−) mice exhibited disorganized apical membrane structure, delayed folliculogenesis, and abnormal formation of thyroid follicle lumina. Conclusion: XB130 critically regulates folliculogenesis by maintaining apical membrane structure and function of thyrocytes, and its deficiency leads to congenital hypothyroidism.

BACKGROUND: The present study investigated whether highly vascularized bronchial arteries affect the intraoperative blood loss and the operative time of video-assisted thoracic surgery (VATS) lobectomy for patients with non-small cell lung cancer. METHODS: We retrospectively collected data on consecutive pathological stage I to IIIA non-small cell lung cancer patients who underwent VATS lobectomy with systematic lymph node dissection between January 2017 and December 2019. Patients were divided into the following two groups according to bronchial artery diameters on preoperative enhanced contrast computed tomography (CT) findings: ≤2 and >2 mm groups. RESULTS: Among the 175 patients enrolled, risk factors for intraoperative blood loss >50 mL were being male (P=0.005), a history of smoking (P=0.01), percent forced expiratory volume in 1 s (FEV1.0%) 2.0 mm (P2.0 mm (P200 min were being male (P2.0 mm (P2.0 mm (P=0.024), and experience of surgeon

Distant metastases derived from papillary carcinoma are generally detected in the lungs and bones. However, renal metastasis is rare. We herein report a case of papillary thyroid carcinoma with renal and pulmonary metastases that had been initially diagnosed as primary renal carcinoma with pulmonary metastases. The lesions showed response to immune checkpoint inhibitors and tyrosine kinase inhibitor but not to radioactive iodine therapy.

OBJECTIVES This study was conducted to verify the optimal extent of lymph node dissection or sampling during lung cancer surgery based on the sentinel node (SN) map created by computed tomography (CT) lymphography. METHODS From April 2010 to January 2015, patients with clinical stage I non-small-cell lung cancer, who were candidates for lobectomy or segmentectomy with standard hilar and mediastinal lymph node dissection, and in whom bronchus reached the tumour, were enrolled. An ultrathin bronchoscope was inserted to the target bronchus under the guidance of virtual bronchoscopic navigation images. CT images of the chest were obtained 30 s after 2.5 ml of iopamidol was injected. SNs were identified when the maximum CT attenuation value of the lymph nodes on postcontrast CT images increased by 30 Hounsfield units or more compared with the precontrast images. Patients underwent lobectomy with standard lymph node dissection. RESULTS SNs were identified in 36 (87.8%) of the 41 patients. The average number of SNs was 1.6 (range, 1–4). There was 1 false negative case; therefore, the accuracy of SN identification was 97.2% (35/36). In 5 (13.9%) of 36 patients, SNs were outside the lobe-specific lymph node station range (#11i from right S1, #7 from right S1, #4R from right S8, #12u from right S8, #7 and #12l from left S1 + 2). CONCLUSIONS CT lymphography demonstrated the diversity of lymphatic spreading patterns and there were cases in which lymph flows are found outside the lymph node dissection range.

Accurate diagnosis of the tracheobronchial invasion of advanced esophageal cancer is essential to select appropriate treatment and improve prognosis; however, it is difficult using the conventional modalities. This study aimed to clarify the diagnostic usefulness of convex probe endobronchial ultrasound (CP-EBUS) for the diagnosis of the tracheobronchial invasion of advanced esophageal cancer. We conducted a cadaveric study to clarify the changes in ultrasonic and histopathologic findings in the esophageal tumor and tracheal invasion models. Additionally, we examined CP-EBUS for patients with advanced thoracic esophageal cancer in whom tracheobronchial invasion was suspected on contrast-enhanced computed tomography (CE-CT) scan. We retrospectivity evaluated the diagnosis of CP-EBUS, comparing the pathological findings and treatment outcomes. Cadaveric esophageal tumor and tracheal invasion models showed the disappearance of the third layer observed with CP-EBUS and histologically proven interruption of the adventitia. This indicated that the third layer corresponded with the tracheal adventitia. We examined 40 patients with advanced thoracic esophageal cancer in whom tracheobronchial invasion was suspected. The precise diagnosis was pathologically confirmed in 9 of 14 patients diagnosed with cT3 who underwent radical surgery. 20 of 26 cases diagnosed with cT4b received definitive chemoradiotherapy, and 4 cases received salvage surgery and pathologically confirmed precise diagnosis. CP-EBUS is extremely useful for diagnosing the tracheobronchial invasion of advanced esophageal cancer. It could be an effective modality for determining treatment strategies in cases with a marginal surgical indication.

Background and objective CBCT-guided TBB using a UTB under VBN is a useful method for the diagnosis of peripheral small pulmonary lesions. CBCT-guided TBB using UTB under VBN has been used as an alternative to CT-guided TBB. However, the advantage of CBCT-guided TBB using UTB under VBN over CT-guided TBB is still unknown. This study aimed to compare the diagnostic yield of CT-guided TBB and CBCT-guided TBB using a propensity score-matched analysis. Methods Patients with peripheral pulmonary lesions ≤30 mm were included. Lesions whose bronchus could not be determined by CT were excluded. A UTB and biopsy forceps were advanced to the target bronchus under VBN, 2D-fluoroscopy and CT or CBCT. The CT-guided and CBCT-guided groups were matched for their propensity scores based on patient characteristics. Results We retrospectively reviewed 93 patients in the CT-guided group and 79 patients in the CBCT-guided group for this study. Furthermore, 48 distinct examination pairs were generated by propensity score matching. In the overall diagnostic yield, the CBCT-guided group showed better results (72.9%) than did the CT-guided group (47.9%) (P = 0.012). The median examination time lasted for 43 (IQR: 37-51) min in the CBCT-guided group and 50 (IQR: 43-62) min in the CT-guided group. The examination time in the CBCT-guided group was significantly shorter than that of the CT-guided group (P = 0.001). Conclusion CBCT-guided TBB had a better diagnostic yield and shorter examination time than did CT-guided TBB.

Background Sentinel node (SN) biopsy is used in the management of numerous cancers to avoid unnecessary lymphadenectomy. This was a clinical exploration/feasibility study of a novel identification technique for SN biopsy using indocyanine green (ICG) fluorescence imaging during lung cancer surgery. Methods SN biopsy using ICG was performed on 22 patients who had cT1 or T2N0M0 lung cancer. ICG was injected just around the primary tumor. The fluorescence imaging system enabled visualization of the lymphatic vessels draining from the primary tumor toward the lymph nodes. Fluorescently labeled nodes were dissected, and patients were followed‐up for prognosis and recurrence to confirm the pattern of lymph node metastasis after surgery. Results SNs were successfully identified in 16 (72.7%) of 22 patients. A total of 13 of 16 patients had pathological N0 and three had SN metastasis. The median follow‐up time was 92.7 months. Only one patient had no SN metastasis at the postoperative pathological examination and lymph node metastasis during the follow‐up period. The accuracy rate was 93.8% (15/16) and the false‐negative rate was 7.7% (1/13). Conclusions SNs were identified by ICG fluorescence imaging, and this technique during lung cancer surgery had good identification and accuracy rates throughout the follow‐up period. Key points Significant findings of the study We attempted to identify sentinel lymph nodes by indocyanine green in lung cancer surgery. The identification rate was 72.7%. The accuracy rate was 100% immediately after surgery, and 93.8% after follow‐up. What this study adds Sentinel node biopsy by indocyanine green may be useful for lymph node dissection during lung cancer surgery to avoid unnecessary lymphadenectomy., We attempted to identify sentinel lymph nodes by indocyanine green in lung cancer surgery. The identification rate was 72.7%, and the accuracy rate was 100% immediately after surgery. In addition, we followed‐up the cases for a long time to check for lymph node metastasis and verify whether the results of intraoperative sentinel biopsy were correct. After follow‐up had been completed, the false‐negative rate was 7.7% (1/13) and the accuracy rate was 93.8% (15/16) in this study.

Background Bronchioalveolar stem cells (BASCs) located at the bronchioalveolar-duct junction (BADJ) are stem cells residing in alveoli and terminal bronchioles that can self-renew and differentiate into alveolar type (AT)-1 cells, AT-2 cells, club cells, and ciliated cells. Following terminal-bronchiole injury, BASCs increase in number and promote repair. However, whether BASCs can be differentiated from mouse-induced pluripotent stem cells (iPSCs) remains unreported, and the therapeutic potential of such cells is unclear. We therefore sought to differentiate BASCs from iPSCs and examine their potential for use in the treatment of epithelial injury in terminal bronchioles. Methods BASCs were induced using a modified protocol for differentiating mouse iPSCs into AT-2 cells. Differentiated iPSCs were intratracheally transplanted into naphthalene-treated mice. The engraftment of BASCs into the BADJ and their subsequent ability to promote repair of injury to the airway epithelium were evaluated. Results Flow cytometric analysis revealed that BASCs represented ~ 7% of the cells obtained. Additionally, ultrastructural analysis of these iPSC-derived BASCs via transmission electron microscopy showed that the cells containing secretory granules harboured microvilli, as well as small and immature lamellar body-like structures. When the differentiated iPSCs were intratracheally transplanted in naphthalene-induced airway epithelium injury, transplanted BASCs were found to be engrafted in the BADJ epithelium and alveolar spaces for 14 days after transplantation and to maintain the BASC phenotype. Notably, repair of the terminal-bronchiole epithelium was markedly promoted after transplantation of the differentiated iPSCs. Conclusions Mouse iPSCs could be differentiated in vitro into cells that display a similar phenotype to BASCs. Given that the differentiated iPSCs promoted epithelial repair in the mouse model of naphthalene-induced airway epithelium injury, this method may serve as a basis for the development of treatments for terminal-bronchiole/alveolar-region disorders.

ObjectiveThe aim of our study was to assess the association between risk of cancer-therapy-related cardiac dysfunction (CTRCD) after first follow-up and the difference in echocardiographic measures from baseline to follow-up.MethodsWe retrospectively enrolled 87 consecutive patients (58±14 years, 55 women) who received anthracycline and underwent echocardiographic examinations both before (baseline) and after initial anthracycline administration (first follow-up). We measured absolute values of global longitudinal strain (GLS), apical longitudinal strain (LS), mid-LS and basal-LS at baseline and first follow-up, and per cent changes (Δ) of these parameters were calculated. Among 61 patients who underwent further echocardiographic examinations (second follow-up, third follow-up, etc), we assessed the association between regional left ventricular (LV) systolic dysfunction from baseline to follow-up and development of CTRCD, defined as LV ejection fraction (LVEF) under 53% and more absolute decrease of 10% from baseline, after first follow-up.ResultsLVEF (65%±4% vs 63±4%, p=0.004), GLS (23.2%±2.6% vs 22.2±2.4%, p=0.005) and basal-LS (21.9%±2.5% vs 19.9±2.4%, pConclusionsBasal-LS significantly decreased prior to development of CTRCD, and worse basal-LS was associated with development of CTRCD in patients receiving anthracycline chemotherapy.

pStage I includes clinicopathologically diverse groups. This study aimed to identify the prognostic factors for pStage I lung adenocarcinoma.We retrospectively reviewed 208 patients with pStage I adenocarcinomas who underwent curative resection in our institute between 2006 and 2013. The maximum standardized uptake value (SUVmax) on [F18]-fluoro-deoxy-D-glucose positron emission tomography-computed tomography (PET/CT) was evaluated. Adenocarcinomas were categorized into the following histologic groups: group 0 (minimally invasive adenocarcinoma and lepidic predominant adenocarcinoma), group 1 (papillary predominant adenocarcinoma), and group 2 (acinar predominant adenocarcinoma and all the remaining subtypes). We assessed the relationship between disease-free survival (DFS) and clinicopathological factors.Multivariate analysis of DFS demonstrated that SUVmax 3.0 (p 0.001), total tumor size 20 mm (p = 0.016), and histologic groups (p 0.05) were independent prognostic factors. The prognostic risk score (PRS) was calculated using the following equation: PRS = SUVmax (≤ 3.0: 0 point, 3.0: 2 points) + total tumor size (≤ 20 mm: 0 point, 20 mm: 1 point) + histologic group (group 0: 0 point, group 1: 1 point, group 2: 2 points). Patients were divided into the following three risk groups: low-risk (PRS 0-2 points, n = 136), intermediate-risk (PRS 3-4 points, n = 49), and high-risk groups (PRS 5 points, n = 13). The 5-year DFS rates were 93.2%, 50.6%, and 30.8% for the low-, intermediate-, and high-risk groups, respectively (p 0.001).The PRS aggregating the FDG-PET/CT SUVmax, total tumor size, and histologic group predicts the prognosis of pStage I lung adenocarcinoma.

Our previous study reported that the DNA methylation of growth hormone secretagogue receptor (GHSR) was significantly higher in thymoma or thymic carcinoma (TC) than in normal thymic tissue samples. Thymic epithelial tumors (TETs) with higher GHSR DNA methylation were associated with significantly worse prognosis than those with lower levels of DNA methylation. Diversified components of the ghrelin-GHSR axis may exert opposing effects in cancer progression, depending on the cancer type in question. However, the precise function of the axis remains unclear. In the present study, the mRNA expression of five key components of the ghrelin system [native ligand ghrelin, variant ligand In-1 ghrelin, native receptor GHSR1a, variant receptor GHSR1b and acylation enzyme ghrelin O-acyltransferase (GOAT)] were examined in 58 TET samples by reverse transcription-quantitative PCR, and protein expression of GHSR1a and GHSR1b was assessed in 20 TETs using immunohistochemistry. The results revealed that In-1 ghrelin, GHSR1b (variant forms) and GOAT were more strongly expressed in thymoma compared with thymic-adjacent tissue. By contrast, no significant differences were observed in the expression of ghrelin and GHSR1a (native forms) between thymoma and thymic tissue. The mRNA expression of In-1 ghrelin and GHSR1b (variant forms) was positively associated with GHSR methylation in thymoma tissue samples. However, a relationship was not found between ghrelin, GHSR1a or GOAT expression (native forms) and GHSR methylation in thymoma. Immunohistochemical analysis revealed that mRNA expression of GHSR1a and GHSR1b generally correlated with expression of the corresponding protein, and that the expression of GHSR1b was increased in advanced-stage TETs. These results indicate that the DNA methylation of GHSR is associated with a shift from native expression (ghrelin and GHSR1a) to variant expression (In-1 ghrelin and GHSR1b), which induces the tumorigenesis of thymoma, but not TC.

Background Visceral pleural invasion (VPI) in lung cancer is a significant prognostic factor; however, it is difficult to diagnose preoperatively or intraoperatively. In this study, we examined the possibility of intraoperative diagnosis of VPI using confocal laser endomicroscopy (CLE). Methods Among patients with primary lung cancer who underwent surgery between April 2018 and August 2019, those in whom the tumor was in contact with the pleura on chest computed tomography and whose pleural changes were intraoperatively confirmed were enrolled in this study. In the 35 patients who underwent lung resection (6 cases with visceral pleural infiltration), the area where pleural change was noted was observed and a short video was recorded using CLE. Based on the video images, three evaluators determined the defect ratio (0%, 25%, 50%, 75%, and 100%) of the autofluorescence-positive structure. The area under the receiver operating characteristic curve was used to evaluate the diagnostic performance for VPI. In 15 cases (3 cases with VPI), a validation study was performed for intraoperative VPI according to the cutoff value of the defect ratio of the autofluorescence-positive structure. Results The areas under the receiver operating characteristic curve for the defect ratio of the autofluorescence-positive structure were 0.86-0.91 for the three readers. Using defect ratio of autofluorescence-positive structure cutoff of ≥50% as predictor of VPI, the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 83.3-100.0%, 57.7-73.1%, 35.3-41.7%, 95.0-100.0%, and 75.0-78.1%, respectively, for the three readers. In the validation study, the sensitivity was 100%, the specificity was 83.3%, and the diagnostic accuracy rate was 86.7%. Conclusions The diagnosis of VPI through CLE is simple, non-invasive, and has high diagnostic accuracy rates. This method may be applicable for determining surgical procedures.

We assessed the diagnostic capacity of dynamic fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) and dual-time-point (DTP) PET/CT to explore the optimal scan timing for nodal staging in lung cancer. Thirty-four patients with lung cancer underwent dynamic and consecutive DTP PET/CT scans. Two readers visually evaluated FDG uptake within each lymph node (LN) and pulmonary artery (metastatic LN: n = 10; nonmetastatic LN: n = 121). For each dynamic and DTP scan, we compared the maximum standardized uptake value (SUVmax) and the retention index of the SUVmax (RI-SUVmax) between metastatic and nonmetastatic LNs. We compared the diagnostic capacity of the dynamic and DTP scans using receiver operating characteristic (ROC) analyses. In the visual analyses of LN metastases, a sensitivity of 20.0–60.0% and specificity of 97.5–100.0% were identified for the first to third dynamic scans. The sensitivity of the 1-h early and 2-h delayed scans was 80.0% and 90.0%, respectively, whereas the specificity was 66.9% and 47.9%, respectively. The visual analysis of the dynamic second phase had the highest accuracy. Semiquantitative analyses revealed that the SUVmax was significantly higher for metastatic LNs than for nonmetastatic LNs in the dynamic second and third phases and the 1-h early and 2-h delayed phases (p 0.05 for all). Based on the visual and semiquantitative analyses, 18F-FDG dynamic PET/CT exhibited excellent performance with extremely high specificity in the dynamic second phase.

Objective : To identify and differentiate patients with mediastinal cysts from those with cystic tumors requiring surgery. Methods : A total of 36 patients with mediastinal cystic lesions were enrolled. The patients were separated into two groups based on pathological findings : those with mediastinal cysts (n=23) and those with mediastinal tumors (n=13). The cystic components were measured using imaging parameters including mean computed tomography (CT) value, apparent diffusion coefficient (ADC), T1 signal intensity ratio (T1SI-ratio), and T2 signal intensity ratio (T2SI-ratio), acquired from magnetic resonance imaging (MRI) ; and standardized maximum uptake value (SUVmax) from 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT). Both groups were statistically compared. Results : Comparative parameters between the cysts and tumors revealed the following ratios : CT value, 40.9±21.2 versus (vs) 24.8±12.9 (p = 0.019) ; SUVmax, 1.18±0.50 vs 4.32±3.52 (p = 0.003) ; ADC, 3.46±0.96 vs 2.68±0.74 (p = 0.022) ; T1SI-ratio, 1.06±0.60 vs 1.35±0.92 (p = 0.648) ; T2SI-ratio, 5.40±1.80 vs 4.33±1.58 (p = 0.194). However, there was no correlation between FDG uptake and ADC value. Conclusions : SUVmax from 18F-FDG PET/CT and ADC derived from MRI were effective in facilitating preoperative diagnosis to differentiate mediastinal cysts from tumors. However, these examinations may be complementary to one another, not dominant.

Background To improve the pathological complete response (pCR) rate, we devised new neoadjuvant chemotherapy. Efficacy and safety of the oral fluoropyrimidine derivative S-1 (Taiho Pharmaceutical Co, Tokyo, Japan) combined with low-dose docetaxel (S-1+DOC) were evaluated. Patients and Methods Patients were treated with docetaxel (40 mg/m2 intravenously on day 1) and S-1 (40 mg/m2 orally twice per day on days 1-14) every 3 weeks for 4 cycles. In accord with the Response Evaluation Criteria In Solid Tumors version 1.1 criteria, the patients who showed a complete response (CR) underwent surgery, and those who achieved a partial response (PR) underwent 4 more cycles of S-1+DOC. Patients who achieved stable disease (SD) or progressive disease (PD) received EC (epirubicin and cyclophosphamide) or HT (trastuzumab and paclitaxel) according to their HER2 status. The primary end point was the pCR rate. Results Ninety-four patients entered the study. After 4 cycles of S-1+DOC, CR was noted in 5 patients, PR in 57, SD in 18, and PD in 3. Of the patients who achieved SD and PD, 12 received EC, and 9 received HT. Among the 83 assessable patients, the pCR rate was 34.9%, and the response rate was 80.7%. The pCR rates were 19.5% in the luminal type group, 53.8% in the luminal HER2 group, 46.1% in the HER2 group, and 50.0% in the triple-negative group. Conclusion The S-1+DOC regimen in this study could be well tolerated and a new candidate neoadjuvant chemotherapy in operable breast cancer patients. It is also expected to be effective even in patients with luminal type disease. However, further randomized control trials are needed to ascertain whether pCR can contribute to favorable outcomes.

Background: Transbronchial biopsy is a safe diagnostic approach for patients with peripheral pulmonary lesions; however, the diagnostic yield is low. Objectives: This study was conducted to evaluate the feasibility and diagnostic yield of transbronchial biopsy using the combination of an ultrathin bronchoscope, virtual bronchoscopic navigation (VBN), and cone-beam computed tomography (CBCT). Methods: Patients with peripheral pulmonary lesions, no >30 mm, with the responsible bronchus, were prospectively included. An ultrathin bronchoscope and biopsy forceps were advanced to the target bronchus under VBN, 2D-fluoroscopy, and CBCT. We categorized the CBCT findings before biopsy into 3 types according to positions of the target lesion and forceps (CBCT target-forceps sign). In type A, the forceps reached the inside of the target lesion. In type C, the forceps could not reach the lesion. When the CBCT findings could not be categorized into either type A or C, the sign was categorized as type B. Results: Although the target lesions were invisible by conventional C-arm fluoroscopy in 29 patients, CBCT visualized all 40 lesions. The overall diagnostic yield was 90.0%, and diagnostic yields for malignant and benign lesions were 92.0 and 86.7%, respectively. Diagnostic yields for CBCT target-forceps sign types A, B, and C were 100, 75.0, and 0%, respectively. Four undiagnosed patients proceeded to other diagnostic procedures based on the CBCT target-forceps sign (type B: n = 2, type C: n = 2) and were correctly diagnosed without delay. Conclusions: Transbronchial biopsy using an ultrathin bronchoscope guided by CBCT and VBN showed a very high yield in the diagnosis of pulmonary nodules.

Thymic epithelial tumors (TETs) comprise thymomas and thymic carcinoma (TC). TC has more aggressive features and a poorer prognosis than thymomas. Genetic and epigenetic alterations in thymomas and TC have been investigated in an attempt to identify novel target molecules for TC. In the present study, genome-wide screening was performed on aberrantly methylated CpG islands in thymomas and TC, and the glutamate decarboxylase 1 gene (GAD1) was identified as the 4th significantly hypermethylated CpG island in TC compared with thymomas. GAD1 catalyzes the production of γ-aminobutyric acid from L-glutamic acid. GAD1 expression is abundant in the brain but rare in other tissues, including the thymus. A total of 73 thymomas and 17 TC tissues were obtained from 90 patients who underwent surgery or biopsy at Tokushima University Hospital between 1990 and 2017. DNA methylation was examined by bisulfite pyrosequencing, and the mRNA and protein expression levels of GAD1 were analyzed using reverse transcription-quantitative PCR and immunohistochemistry, respectively. The DNA methylation levels of GAD1 were significantly higher in TC tissues than in the normal thymus and thymoma tissues, and GAD1 methylation exhibited high sensitivity and specificity for discriminating between TC and thymoma. The mRNA and protein expression levels of GAD1 were significantly higher in TC tissues than in thymomas. Patients with TET with high GAD1 DNA hypermethylation and high mRNA and protein expression levels had significantly shorter relapse-free survival rates than those with low levels. In conclusion, significantly more epigenetic alterations were observed in TC tissues compared with in thymomas, which may contribute to the clinical features and prognosis of patients.

Purpose: To investigate the relation of absolute lymphocyte count (ALC) changes during neoadjuvant chemotherapy for human epidermal growth factor receptor-2 (HER2)-positive breast cancer patients and their prognosis.Methods: From January 2010 to December 2019, patients diagnosed with HER2-positive breast cancer and treated with trastuzumab-based neoadjuvant chemotherapy (NAC) were included in this retrospective cohort study. The ALC ratio was Blood cell count estimates before and after NAC were evaluated to calculate the ALC ratio. The optimal cut-off for the ALC ratio was identified using the receiver operating characteristic (ROC) curve analysis and Youden’s index. The relationship between the ALC ratio and disease-free survival (DFS) was measured using the Kaplan–Meier method. Univariate and multivariate analyses were performed using the Cox proportional hazards model.Results: 71 HER2 breast cancer patients were analyzed. The cut-off value of the ALC ratio was decided as 1.109. The median follow-up period was 53.1 (range: 5.1-111.5) months. The high-ALC ratio group showed superior survival rates to the low-ALC ratio group (p=0.0242). The 5-year DFS rates were 89.1% and 63.3% in the high- and low-ALC ratio group, respectively. The ALC ratio was nominated as an independent prognostic factor in multivariate Cox proportional hazards analysis (p=0.0052).Conclusion: HER2-positive breast cancer patients who showed a higher ALC ratio during trastuzumab-based neoadjuvant chemotherapy were associated to better survival.

OBJECTIVE To semiquantitatively estimate fluorine-18-fluorodeoxyglucose (FDG) uptake in primary lung cancer cells using dynamic and dual-time-point (DTP) PET/computed tomography (PET/CT) to obtain a diagnostic index for lymph node metastasis. METHODS Forty-five patients with lung cancer underwent dynamic and DTP PET/CT examinations. All primary lesions and lymph node metastases were evaluated pathologically. At each time phase, we assessed the maximum standardised uptake value (SUVmax), metabolic tumour volume (MTV) and total lesion glycolysis (TLG) of the primary tumours. We investigated the relationship between semiquantitative index and the presence of lymph node metastasis for each case and for all cases satisfying indications for segmentectomy. In cases with lymph node metastasis, we assessed the SUVmax of pathologically proven metastatic lymph nodes and nonmetastatic lymph nodes in each dynamic phase for evaluating temporal change. RESULTS Among 45 patients, 15 had 17 lymph node metastasis. SUVmax, MTV and TLG of primary tumours at each time phase were significantly associated with lymph node metastasis (P

Purpose To evaluate the efficacy, toxicity, maximum tolerated dose, and recommended dose of triweekly nab-paclitaxel (nab-PTX) and S-1 combination chemotherapy for patients with metastatic breast cancer. Patients and Methods This phase 1 study was conducted with a standard 3 + 3 dose escalation design. Every 3 weeks, the patients received nab-PTX at 180-260 mg/m2 on day 1 and S-1 at 65-80 mg/m2 daily on days 1 to 14. Results Ten HER2-negative metastatic breast cancer patients were enrolled; their median number of prior chemotherapy regimens was 3. Dose-limiting toxicity was observed in the first patient assigned to level 4; grade 4 febrile neutropenia and grade 3 neurotoxicity such as needing a wheelchair occurred. Therefore, an additional patient was not assigned to level 4. The maximum tolerated dose was considered level 4 (260 mg/m2 nab-PTX with 80 mg/m2 S-1). The recommended dose determined was level 3 (220 mg/m2 nab-PTX with 80 mg/m2 S-1). The response rate was 60.0%. The disease control rate was 70.0%. Conclusion This combination chemotherapy therapy was feasible and safe for patients with HER2-negative metastatic breast cancer.

There is currently no consensus regarding the best program for postoperative follow-up and surveillance after a curative resection for non-small-cell lung cancer (NSCLC) patients. We examined the diagnostic capability of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) for detecting recurrence in postoperative NSCLC patients, and we evaluated the results of postoperative surveillance using FDG-PET/CT in asymptomatic patients. Between 2005 and 2013, 496 FDG-PET/CT examinations were performed to detect recurrences for 187 NSCLC patients who had undergone potentially curative operations at our institution. Follow-up FDG-PET/CT was performed ≥ 1 × /year in principle in 172 asymptomatic patients without clinical or radiological evidence of recurrence, and the results were retrospectively reviewed. FDG-PET/CT correctly diagnosed recurrence in 46 of 47 (97.9%) patients and 68 of 69 (98.6%) recurrent sites. The following were obtained: 97.9% sensitivity, 97.1% specificity, 92.0% positive predictive value, 99.3% negative predictive value, and 97.3% accuracy. In six patients, other diseases were detected and treated appropriately. In asymptomatic patients, the detection rate of recurrence in the stage III group was significantly higher than the detection rates in the stage I and II groups, and FDG-PET/CT performed ≤ 3 years post-resection detected significantly more FDG-positive lesions compared to that performed after 4 years. FDG-PET/CT is very useful for detecting recurrence in NSCLC patients after a potentially curative operation. It might be sufficient to perform follow-up FDG-PET/CT until 3 years post-resection for advanced-stage patients. Further randomized clinical trials are needed to determine whether the early detection of recurrences leads to better prognoses.

Thymic epithelial tumors comprise thymoma, thymic carcinoma and neuroendocrine tumors of the thymus. Recent studies have revealed that the incidence of somatic non‑synonymous mutations is significantly higher in thymic carcinoma than in thymoma. However, limited information is currently available on epigenetic alterations in these types of cancer. In this study, we thus performed genome‑wide screening of aberrantly methylated CpG islands in thymoma and thymic carcinoma using Illumina HumanMethylation450 K BeadChip. We identified 92 CpG islands significantly hypermethylated in thymic carcinoma in relation to thymoma and selected G protein subunit gamma 4 (GNG4), growth hormone secretagogue receptor (GHSR), homeobox D9 (HOXD9) and spalt like transcription factor 3 (SALL3), which are related to cancer. We examined the promoter methylation of 4 genes in 46 thymic epithelial tumors and 20 paired thymus tissues using bisulfite pyrosequencing. Promoter methylation was significantly higher in thymic carcinoma than in thymoma and revealed a high discrimination between thymic carcinoma and thymoma in all 4 genes. Promoter methylation was higher in thymic carcinoma than in the thymus. No significant differences were observed in the promoter methylation of GNG4, HOXD9, or SALL3 between thymoma and the thymus. The promoter methylation of the 4 genes was not significantly higher in advanced‑stage tumors than in early‑stage tumors in all thymic epithelial tumors. Among the 4 genes, relapse‑free survival was significantly worse in tumors with a higher DNA methylation than in those with a lower DNA methylation in all thymic epithelial tumors. Moreover, relapse‑free survival was significantly worse in thymomas with a higher DNA methylation of HOXD9 and SALL3 than in those with a lower DNA methylation. On the whole, the findings of this study indicated that the promoter methylation of cancer‑related genes was significantly higher in thymic carcinoma than in thymoma and the thymus. This is a common epigenetic alteration of high diagnostic value in thymic carcinoma and may be involved in the carcinogenesis of thymic carcinoma. However, epigenetic alterations in the 3 genes, apart from GHSR, are not involved in the tumorigenesis of thymoma.

Adjuvant chemotherapy with uracil tegafur (UFT) improved survival among patients with completely resected stage I lung adenocarcinoma. S-1, an oral dihydropyrimidine dehydrogenase (DPD)-inhibitory 5-fluorouracil, is a more potent DPD inhibitor than UFT;therefore, we hypothesized that postoperative adjuvant chemotherapy with S-1 would be effective for advanced non-small cell lung cancer (NSCLC). We conducted a feasibility study of S-1 as postoperative adjuvant chemotherapy in patients with curatively resected pathological stage bold I back 10 bold I and bold I back 10 bold I back 20 bold I A NSCLC.Adjuvant chemotherapy consisted of 9 courses (4-week administration, 2-week withdrawal) of S-1 at 80-120 mg/body per day. Twenty-four patients with completely resected NSCLC were enrolled in this study from November 2007 through December 2010. The primary endpoint was the rate of completion of the scheduled adjuvant chemotherapy. The secondary endpoints were safety, overall survival, and relapse-free survival.Five patients were censored because of disease recurrence. The planned 9 courses of S-1 were administered to completion in 8 patients. Twelve patients completed more than 70% of the planned courses. Grade 3 adverse reactions, such as elevated total bilirubin (4.2%) and pneumonitis (4.2%), were observed, but there were no Grade 4 adverse reactions. Patients who completed more than 70% of the 9 courses demonstrated better overall survival than those who completed less than 70%.Postoperative administration of S-1 may be possible with few severe adverse events as adjuvant chemotherapy for patients with curatively resected pathological stage bold I back 10 bold I -bold I back 10 bold I back 20 bold I A NSCLC. J. Med. Invest. 65:90-95, February, 2018.

Highlights • Medial basal segmentectomy is uncommon procedure. • It is difficult to perform the procedure because of anatomical variations. • This is a rare report of thoracoscopic medial basal segmentectomy., Introduction Isolated resection of the medial basal segment (S7) is uncommon because of its small volume, and S7 segmentectomy is considered to be difficult due to anatomical variation. We report a case of successful thoracoscopic S7 segmentectomy. Presentation of case A 56-year-old man was referred to our hospital with suspected pulmonary metastasis of rectal cancer. A 6-mm nodule was detected in S7. A7 and B7 branched from the basal segmental artery and bronchus, respectively, to run ventral to the inferior pulmonary vein. This made it possible to isolate A7 and B7 by an approach via the interlobar fissure. In addition, V7a and V7b were easily isolated from inferior pulmonary vein. The intersegmental plane was indicated by V7b and was transected along a demarcation line identified by using selective oxygenation via B7. Discussion B7 most commonly branches from the basal bronchus and A7 from the basal artery to run ventral to the inferior pulmonary vein. With this anatomical type, when the surgeon approaches via the interlobar fissure during surgery, A7 is identified first, B7 is seen behind A7, and the IPV is posterior to B7. Since the intersegmental plane is located ventral to the IPV, segmentectomy can be completed via the interlobar fissure approach. Conclusion In patients with this pattern of pulmonary artery and bronchial anatomy, isolated S7 segmentectomy is a feasible treatment option.

Background Daikenchuto (TJ-100), a traditional Japanese herbal medicine, is widely used in Japan. Its effects on gastrointestinal motility and microcirculation and its anti-inflammatory effect are known. The purpose of this prospective randomized controlled trial was to investigate the effect of TJ-100 after esophagectomy in esophageal cancer patients. Methods Forty patients for whom subtotal esophageal resection for esophageal cancer was planned at our institute from March 2011 to August 2013 were enrolled and divided into two groups at the point of determination of the operation schedule after informed consent was obtained: a TJ-100 (15 g/day)-treated group (n = 20) and a control group (n = 20). The primary efficacy end-points were maintenance of the nutrition condition and the recovery of gastrointestinal function. The secondary efficacy end-points were the serum C-reactive protein (CRP) level and adrenomedullin level during the postoperative course, the incidence of postoperative complications, and the length of hospital stay after surgery. Results We examined 39 patients because one patient in the TJ-100 group was judged as having unresectable cancer after surgery. The mean age of the TJ-100 group patients was significantly older than that of the control group patients.The rate of body weight decrease at postoperative day 21 was significantly suppressed in the TJ-100 group (3.6% vs. the control group: 7.0%, p = 0.014), but the serum albumin level was not significantly different between the groups. The recovery of gastrointestinal function regarding flatus, defecation, and oral intake showed no significant between-group differences, but postoperative bowel symptoms tended to be rare in the TJ-100 group. There was no significant between-group difference in the length of hospital stay after surgery. The serum CRP level at postoperative day 3 was 4.9 mg/dl in the TJ-100 group and 6.9 mg/dl in the control group, showing a tendency of a suppressed serum CRP level in the TJ-100 group (p = 0.126). The rate of increase in adrenomedullin tended to be high postoperatively, but there was no significant difference between the two groups. Conclusions TJ-100 treatment after esophageal cancer resection has the effects of prompting the recovery of gastrointestinal motility and minimizing body weight loss, and it might suppress the excess inflammatory reaction related to surgery.

Objectives This study was conducted to evaluate the accuracy of autofluorescence as a mode of diagnosis for visceral pleural invasion of non-small-cell lung cancer compared with white-light by means of clinical questions to several thoracic surgeons. Methods Eight independent thoracic surgeons evaluated visceral pleural invasion in 25 cases of non-small-cell lung cancer attached to the visceral pleura on lung windows of preoperative computed tomography images. At the first study meeting to evaluate the accuracy of visceral pleural invasion diagnosis using conventional white-light images, the surgeons diagnosed visceral pleural invasion based on information in preoperative computed tomography images, histological types and videos recorded with white-light mode using a thoracoscope. At the second study meeting to evaluate the accuracy of visceral pleural invasion diagnosis using autofluorescence, the same surgeons diagnosed visceral pleural invasion based on information in 2 videos recorded in white-light mode and in autofluorescence mode using the thoracoscope. Results The overall average sensitivity, specificity and accuracy of visceral pleural invasion diagnosis by white-light versus autofluorescence mode were 64.6% vs 83.3%, 53.9% vs 73.7% and 56.5% vs 76.0%, respectively. Conclusions The sensitivity, specificity and accuracy of visceral pleural invasion diagnosis was improved through the additional use of the autofluorescence mode compared with the white-light mode alone.

We present a case of type A thymoma with invasion of the left brachiocephalic vein and lung metastases. An 84-year-old man underwent extended thymectomy combined with left brachiocephalic vein reconstruction and resection of a lung metastasis. Histological examination showed vascular invasion by the tumor. The lung metastasis had high mitotic activity and slight nuclear enlargement, the so-called "atypical" features, but the main part of the primary tumor did not. However, the intravascular portion of the tumor had "atypical" histological features like the lung metastasis. It seems that "atypical" histological features are related to clinically malignant behavior.

Background: Indocyanine green (ICG) accumulates in hepatocellular carcinoma (HCC), and tumor fluorescence can be observed under irradiation with near infrared light (NIR). This study investigated the clinical utility of ICG fluorescence imaging during resection of pulmonary metastases of HCC. Methods: From April 2010 to June 2018, six patients with suspected pulmonary metastasis of HCC were enrolled prospectively. Prior to surgery, all patients underwent the ICG hepatic function test following intravenous administration of ICG (0.5 mg/kg body weight). During surgery, metastatic HCC was identified by observation of ICG fluorescence, allowing assessment of the surgical margin. Tumor fluorescence was also evaluated on cut sections. Results: A total of 11 metastatic HCCs were resected in six patients at nine operations. Eight lesions were removed by wedge resection and 3 lesions were managed by lobectomy. During surgery, tumor fluorescence could be confirmed through the visceral pleura in 6 out of 7 lesions treated by wedge resection, while NIR irradiation was difficult for 1 lesion. For these 6 lesions, the median distance from the tumor to the visceral pleura and the median surgical margin were 0 mm (range, 0–2 mm) and 14 mm (range, 11–17 mm), respectively. When cut sections were examined, all tumors emitted fluorescence. All lesions were histologically confirmed to be metastatic HCC. Conclusions: In patients with pulmonary metastasis of HCC, ICG fluorescence imaging is useful for identifying the tumor and securing its margin when the lesion is peripheral and wedge resection is planned.

Sentinel lymph node (SLN) navigation surgery became the routine clinical procedure in breast cancer (BC) surgery. SLN navigation has also been introduced to gastrointestinal cancer but still remains controversial for esophageal cancer, because the lymphatic network spread widely from the abdomen to the neck compared with gastric and colon cancer. We developed SLN navigation surgery using multidetector (MD) computed tomography lymphography (CTLG) with a water-soluble iodine tracer injection in BC, which predict not only the precise number and location of the SLNs but also the existence of lymph node metastasis surrounding detailed anatomy, during a screening CT for metastasis.

We assessed the diagnostic capacity of dynamic fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography (Thirty-four patients with lung cancer underwent dynamic and consecutive DTP PET/CT scans. Two readers visually evaluated FDG uptake within each lymph node (LN) and pulmonary artery (metastatic LN: n = 10; nonmetastatic LN: n = 121). For each dynamic and DTP scan, we compared the maximum standardized uptake value (SUVmax) and the retention index of the SUVmax (RI-SUVmax) between metastatic and nonmetastatic LNs. We compared the diagnostic capacity of the dynamic and DTP scans using receiver operating characteristic (ROC) analyses.In the visual analyses of LN metastases, a sensitivity of 20.0-60.0% and specificity of 97.5-100.0% were identified for the first to third dynamic scans. The sensitivity of the 1-h early and 2-h delayed scans was 80.0% and 90.0%, respectively, whereas the specificity was 66.9% and 47.9%, respectively. The visual analysis of the dynamic second phase had the highest accuracy. Semiquantitative analyses revealed that the SUVmax was significantly higher for metastatic LNs than for nonmetastatic LNs in the dynamic second and third phases and the 1-h early and 2-h delayed phases (p 0.05 for all). The RI-SUVmax was higher in metastatic LNs than in nonmetastatic LNs for the dynamic scan (p = 0.004) and the DTP scan (p = 0.002). The ROC analyses showed that SUV2 and SUV3 had higher performances with high specificity, high negative predictive value, and high accuracy than the other parameters. The area under the ROC curve of the RI-SUV-dual-time-point had the highest value (0.794) without any significant differences between the area under the ROC curves for all parameters (p 0.05 for all).Based on the visual and semiquantitative analyses