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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.

A 67-year-old man was admitted to our hospital for massive pleural effusion. He had a history of mandibular gingival carcinoma treated with radiation therapy (RT). Based on the cytology findings of pleural effusion and a thoracoscopic pleural biopsy, we finally diagnosed him with radiation-associated angiosarcoma. Retrospective cell-block immunocytochemistry with pleural effusion also showed potential utility for the diagnosis. This case highlights the importance of considering the possibility of radiation-associated secondary cancer in patients with pleural effusion who have a history of RT.

Drug-induced interstitial pneumonia (DIP) that occurs during chemotherapy for breast cancer is a rare but a serious adverse event. Treatments of DIP requires interruption of breast cancer treatment, which may affect the patient's prognosis. However, there are few reports which discuss DIP during breast cancer treatments. Purpose of this report is to make clear how DIP occurred and influenced breast cancer treatment in our hospital.A total of 74 patients who started perioperative chemotherapy in Tokushima Municipal Hospital for breast cancer from January 2019 to December 2020 were evaluated for DIP. Patients' and tumors' characteristics, and regimens which caused DIP were investigated. The clinical courses of the DIP patients were also followed up.Twelve of the 74 patients developed DIP. All 12 patients had histories of cyclophosphamide administration;however, the causative drug could not be determined. Ten of the 12 patients were treated with steroids, and all the patients recovered ultimately from the interstitial pneumonia. While chemotherapy was administered in six patients after mild DIP, no relapse of pneumonia was observed.DIP during perioperative chemotherapy for breast cancer was resolved with appropriate treatment. Patients were able to resume breast cancer treatment with minimal interruption. J. Med. Invest. 69 : 107-111, February, 2022.

Histopathological tumor regression grade is applied not to lymph nodes but primary tumors modified by preoperative treatments. This study focused on patients whose pathological examination at the time of surgery showed no residual tumor after chemo(radio)therapy in the primary lesion (ypT0) or lymph nodes (ypN0).A total of 87 patients with clinical stage II/III thoracic esophageal cancer underwent esophagectomy following preoperative treatments to evaluate significances between pathological response and clinical outcomes; 51 patients with clinically definitive lymph node metastasis (cN+) were analyzed as a subgroup.ypT0 rates were 20.7% and 23.5%, and ypN0 rates were 47.1% and 27.5% in the whole cohort and in the cN+ subgroup, respectively. Disease-free survival, from surgery to relapse or death, was significantly influenced by ypN status (p=0.035) but not by ypT status in the 51 patients with definitive cN+ disease. Preoperative chemoradiation was an independent favorable factor for achievement of ypN0 in the 51 patients (odds ratio=0.09; p=0.007).ypN status was a predictive factor for DFS in patients treated with docetaxel plus low-dose 5-fluorouracil and cisplatin combined chemotherapy, superior to ypT status, especially in patients with definitive cN+ disease.

BACKGROUND: Visceral pleural invasion (VPI) is a clinical manifestation associated with a poor prognosis, and diagnosing it preoperatively is highly imperative for successful sublobar resection of these peripheral tumors. We evaluated the roles of computed tomography (CT) features and circulating tumor cells (CTCs) for improving VPI detection in patients with clinical T1N0M0 invasive lung adenocarcinoma. METHODS: Three hundred and ninety-one patients were reviewed retrospectively in this study, of which 234 presented with a pleural tag or pleural contact on CT images. CTCs positive for the foliate receptors were enriched and analyzed prior to surgery. Logistic regression analyses were performed to assess the association of CT features and CTCs with VPI, and the receiver operating characteristic (ROC) curve was generated to compare the predictive power of these variables. RESULTS: Patients mostly underwent either segmentectomies (18.9%) or lobectomies (79.0%). Only 49 of the 234 patients with pleural involvement on CT showed pathologically confirmed VPI. Multivariate logistic regression analysis revealed that CTC level ≥10.42 FU/3 mL was a significant VPI risk factor for invasive adenocarcinoma cases ≤30 mm [adjusted odds ratio (OR) =4.62, 95% confidence interval (CI): 2.05–10.44, P

Purpose The aim of the present study was to investigate the efficacy of a new upper limb fixation method—body pillow position for preventing postoperative ipsilateral shoulder pain (ISP) in patients undergoing lung resection. Design An experimental study design was used. Methods We conducted two comparisons (group A: the previous position using the arm fixation device; group B: the body pillow position) at random and examined an arm fixation method that is effective for ISP prophylaxis in patients undergoing surgery in the lateral decubitus position. Findings We approached 87 patients, two were excluded, and, thus, 85 were randomly assigned to group A (n = 43) or group B (n = 42). No significant differences were observed in the frequency of ISP between groups A and B (25.6% vs 26.2%). The intensity of ISP between both groups was analyzed by a repeated-measures analysis of variance and was shown to decrease over time in 22 patients (P = .010). The intensity of ISP on postoperative days 0 to 3 was slightly lower in group B than in group A (P = .158). Risk factors for ISP were the duration of surgery (odds ratio, 1.01; 95% confidence interval, 1.00 to 1.01) and pre-existing shoulder stiffness (odds ratio, 5.15; 95% confidence interval, 1.07 to 24.83). Conclusions There was no significance in the frequency of ISP between group A and group B. The intensity of ISP on postoperative days 0 to 3 was lower in group B than in group A, although there was no significant difference. It is important perspective for perioperative care providers to prevent ISP for early postoperative recovery and improvement of postoperative quality of life. These results suggested that we must consider a better position for preventing postoperative ISP in patients undergoing lung resection.

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

Fibrocytes, which are bone marrow-derived collagen-producing cells, have been reported to be involved in pathogenesis of pulmonary fibrosis. Our previous study reported that tumor-infiltrating fibrocytes play a role in tumor progression and drug resistance in lung cancer. The present study therefore examined chemotactic factors for fibrocytes in tissues of non-small cell lung cancer (NSCLC) and their prognostic significance. Surgically resected tumor tissues were examined for the expression of chemotactic factors, including C-X-C motif chemokine 12 (CXCL12), CCL2, platelet-derived growth factor (PDGF)-AA and PDGF-BB, as well as tumor-infiltrating fibrocytes by immunostaining. The chemotactic ability of fibrocytes in response to each factor was evaluated using a migration assay by counting the migrated cells microscopically, and expression of receptors for chemotactic factors were analyzed by flow cytometry. The expression of CXCL12, but not CCL2, PDGF-AA, or PDGF-BB, was associated with the number of tumor-infiltrating fibrocytes in lung adenocarcinoma (LUAD), but not lung squamous cell carcinoma (LUSQ). In addition, patients with an increased expression of CXCL12 in LUAD but not LUSQ showed a significantly poorer prognosis compared with those with a decreased expression. However, the expression of CCL2, PDGF-AA and PDGF-BB was not correlated with the prognosis of patients with NSCLC. The number of fibrocytes was associated with a poor prognosis in LUAD. Fibrocytes derived from the peripheral blood of healthy subjects as well as patients with lung cancer expressed higher levels of CXCR4 compared with CCR2, PDGF and receptor-α and receptor-β. Overall, these results suggested that targeting tumor-infiltrating fibrocytes via the CXCL12/CXCR4 axis may be a useful strategy for controlling the progression of NSCLC, particularly LUAD.

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.

Background Localization of small pulmonary nodules (SPNs) is challenging in minimally invasive pulmonary resection, and it is unknown whether computer tomography (CT) guided by indocyanine green (ICG) can provide accurate localization with minimal complications. Methods We performed a retrospective study of patients who underwent thoracoscopic resection of pulmonary nodules after CT-guided preoperative localization with ICG from May 2019 to May 2020. Demographics, procedural data, postoperative complications, and pathologic information, were collected, and an analysis of the accuracy and complications after surgery was conducted. Results In 471 patients, there was a total of 512 peripheral pulmonary nodules that were ≤2 cm in size. The average time for CT-guided percutaneous ICG injection for localization was 18 minutes, and 98.4% (504/512) of the nodules were successfully localized. The average size of the nodules was 9.1 mm, and the average depth from the pleural surface was 8.9 mm. Overall, 5.9% (28/471) of the patients had asymptomatic pneumothorax after localization, but none needed a tube thoracostomy. All the nodules were resected using video-assisted thoracoscopy technique. Conclusions Preoperative CT-guided transthoracic ICG injection is safe and feasible for localization of small lung nodules for minimally invasive pulmonary resection. This technique should be considered for preoperative CT-guided localization of small lung nodules.

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.

In this report, we describe a rare case of vagus nerve schwannoma associated with esophageal cancer. A 70-year-old man visited our hospital complaining of worsening dysphagia. His upper gastrointenstinal endoscopy revealed a mass in the esophagus. A contrast-enhanced chest computed tomography also detected a 15 mm nodule attached to the tracheal membrane. This nodule was diagnosed as a metastatic lymph node. Although the primary tumor reduced after neoadjuvant chemotherapy, the nodule remained intact ; it showed fluorodeoxyglucose accumulation on positron emission tomography. We had a clinical diagnosis of stage III after neoadjuvant chemotherapy and underwent surgery. Intraoperatively, the nodule could not be detached from the right vagus nerve ; therefore, we excised the nodule along with the adjacent vagus nerve. The nodule was pathologically diagnosed as a vagus schwannoma. The nodule was not a regional lymph node metastasis of esophageal cancer. His postoperative course was uneventful, and he is currently undergoing outpatient follow-up without recurrence. J. Med. Invest. 68 : 205-208, February, 2021.

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.

The intraoperative identification and preservation of the parathyroid glands are vital techniques, which are largely dependent on a surgeon’s experience. Therefore, a simple and reproducible technique to identify the parathyroid glands during surgery is needed. Parathyroid tissue shows near-infrared (NIR) autofluorescence, which enables the intraoperative identification of the parathyroid gland. We herein present two cases that underwent surgery on the parathyroid glands, which were observed using the NIR fluorescence imaging system LIGHTVISION(®) (Shimazu, Kyoto, Japan). In a case of papillary thyroid carcinoma, the system was adopted to preserve normal parathyroid glands during left hemithyroidectomy. The left lower parathyroid gland was identified using the imaging system under white light; however, its autofluorescence was visualized more clearly with the excitation light of NIR. In a case of primary hyperparathyroidism due to MEN1, the system was adopted to identify and remove all of the parathyroid glands during total parathyroidectomy. The autofluorescence of diseased glands was weaker than that of normal glands, even with the excitation light of NIR. When the parathyroid glands were irradiated with a red laser pointer, the intensity of autofluorescence significantly increased. However, the largest gland, which was pathologically proven to contain strongly proliferating chief cells, did not show autofluorescence. These results suggest that normal or less diseased parathyroid glands, which are generally small and difficult to identify during surgery, showed relatively strong autofluorescence. A stronger excitation light increases the autofluorescence of parathyroid glands, which enhances sensitivity for detecting parathyroid glands during surgery. In conclusion, LIGHTVISION(®) is a useful device to identify parathyroid glands and an additional excitation light of a red laser pointer increases the detection sensitivity.

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.

Introduction : Central venous catheter (CVC) use is essential for treating esophageal cancer. Peripherally inserted central catheters (PICC) are commonly used recently for improved patient comfort and safety. We compared centrally inserted central catheters (CICC) and PICC insertions and examined their safety. Methods : We retrospectively investigated complications at the catheter insertion and post-insertion for 199 patients' esophageal cancer treatment (CICC : 45, PICC : 154) from 2013 to 2018. In addition, we summarized the results of catheter tip culture. Results : No serious complications occurred at the catheter insertion in either group. The rate of complications at catheter insertion was 5.8% for PICC and 6.7% for CICC patients. Post-insertion complications were observed in 6.5% and 11.1% of patients with PICC and CICC, respectively, and this difference was not significant. The incidence of catheter-related blood stream infection (CRBSI) was significantly lower in PICC than CICC patients (0.3 vs. 1.8 / 1,000 catheter-days ; p = 0.029). Catheter-related thrombosis was observed in PICC : 0.5 and CICC : 0.6, and occlusion due to blood flow reversal was observed in PICC : 0.5 and CICC : 0.6. Conclusion : PICCs are safer and more effective than CICCs for the treatment of esophageal cancer, and reduce the incidence of CRBSI. We hope to standardize the insertion procedures, conventionalize techniques, and establish training systems. J. Med. Invest. 67 : 298-303, August, 2020.

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.

Anastomotic leakage (AL) is a serious complication after esophagectomy. The retrosternal (RS) route has been selected majorly to reduce reflux and related pneumonia and considering mediastinal recurrences. AL has been developed more in RS than posterior mediastinal (PM) route reconstruction. Therefore, we suspected the sterno-tracheal distance (STD) might be related to AL and started the selection according to the STD from 2009. A total of 221 patients who underwent a subtotal esophagectomy with gastric tube reconstruction during January 2004–April 2017 were investigated. The patients were classified into the ‘after STD selection’ (A; n = 144) group and the ‘before STD selection’ (B, n = 77) group. The incidences of and the risk factors for AL between the two groups were compared. The incidence of AL was high in the B group (18.2%), and 78.6% of the patients who developed AL were treated with RS route reconstruction. The median STDs of the patients with AL and no AL were 10.3 mm and 14.5 mm, respectively (p = 0.001). These results demonstrated that the STD was a risk factor for AL in the RS route. Based on these results, 13 mm was set as the cutoff value. After STD selection, the median STD increased from 14.0 to 17.3 mm (p = 0.001), and the incidence of AL decreased significantly from 26.2 to 11.1% in the RS route (p = 0.037). The STD was the independent risk factor for AL in the RS route. RS route reconstruction should be avoided for the patients with STD

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.

Background and Objectives In a previous genome‐wide screening, we identified hypermethylated CpG islands around glutamate decarboxylase 1 (GAD1) in lung adenocarcinoma (LADC). In this study, we aimed to investigate the methylation and expression status of GAD1 and its prognostic value in patients with LADC. Methods GAD1 methylation and mRNA expression status were analyzed using 33 tumorous and paired non‐tumorous LADC samples and publicly available datasets. The prognostic value of GAD1 overexpression was investigated using publicly available datasets of mRNA levels and 162 cases of LADC by immunohistochemistry. Results The methylation and mRNA expression levels of GAD1, each having a positive correlation, were significantly higher in LADC tumors than in paired non‐tumorous tissues. LADC patients with higher GAD1 mRNA expression showed significantly poorer prognosis for overall survival in publicly available datasets. Higher immunoreactivity of GAD1 was significantly associated with the pathological stage, pleural invasion, lymph vessel invasion, and poorer prognosis for cancer‐specific and disease‐free survival. Multivariate analysis revealed that GAD1 protein overexpression is an independent prognosticator for disease‐free survival. Conclusions GAD1 mRNA and protein expression levels were significant prognostic factors in LADC, suggesting that they might be useful biomarkers to stratify patients with worse clinical outcomes after resection.

Neoplasm of a colonic graft after esophageal reconstruction is rare. We treated a colon cancer patient who developed malignancy in a colonic graft after esophagectomy and reconstruction through a retrosternal route. A male had undergone esophagectomy in his 50s due to a benign esophago-bronchial fistula. His dysphagia became exacerbated 20 years later, and further examinations showed a circumferential tumor on the esophagocolonic anastomosis. He underwent resection of the colonic graft adenocarcinoma with median sternotomy after neoadjuvant chemotherapy. Gastric tube reconstruction was performed through a retrosternal route. This report should be informative in terms of making decisions from an initial reconstruction to follow-up and choosing a therapeutic strategy for colonic graft cancer in the future. J. Med. Invest. 66 : 190-193, February, 2019.

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: 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.

Objectives Virtual-assisted lung mapping 2.0 is a novel preoperative bronchoscopic lung mapping technique combining the multiple dye marks of conventional virtual-assisted lung mapping with intrabronchial microcoils to navigate thoracoscopic deep lung resection. This study's purpose was to evaluate the feasibility of virtual-assisted lung mapping 2.0 in resecting deeply located pulmonary nodules with adequate margins. Methods A multicenter, prospective single-arm study was performed from 2019 to 2020 in 8 institutions. The selection criteria were barely identifiable nodules requiring sublobar lung resections, nodules requiring resection lines reaching the inner 2/3 of the pulmonary lobe on computed tomography images in wedge resection, or the nodule center located in the inner 2/3 of the pulmonary lobe in wedge resection or segmentectomy. Resection margins larger than 2 cm or the nodule diameter were considered successful resection. Bronchoscopic placement of multiple dye marks and microcoil(s) was conducted 0 to 2 days before surgery. Results We analyzed 65 lesions in 64 patients. The diameter and depth of the targeted nodules and the minimum required resection depth reported as median (interquartile range) were 9 (7-13) mm, 11 (5-15) mm, and 30 (25-35) mm, respectively. Among 60 wedge resections and 5 segmentectomies, successful resection was achieved in 64 of 65 resections (98.5%; 95% confidence interval, 91.7-100). Among 75 microcoils placed, 3 showed major displacement after bronchoscopic placement. There were no severe adverse events associated with the virtual-assisted lung mapping procedure. Conclusions This study demonstrated that virtual-assisted lung mapping 2.0 can facilitate successful resections for deep pulmonary nodules, overcoming the limitations of conventional virtual-assisted lung mapping.

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.

Background: A displaced left B1+2 accompanied by an anomalous pulmonary vein is a rare condition involving complex structures. There is a risk of unexpected injuries to bronchi and blood vessels when patients with such anomalies undergo surgery for lung cancer.Case presentation: A 59-year-old male with suspected lung cancer in the left lower lobe was scheduled to undergo surgery. Chest computed tomography revealed a displaced B1+2 and hyperlobulation between S1+2 and S3, while the interlobar fissure between S1+2 and S6 was completely fused. Three-dimensional computed tomography (3D-CT) revealed an anomalous V1+2 joining the left inferior pulmonary vein and a branch of the V1+2 running between S1+2 and S6. We performed left lower lobectomy via video-assisted thoracic surgery, while taking care with the abovementioned anatomical structures. The strategy employed in this operation was to preserve V1+2 and confirm the locations of B1+2 and B6 when dividing the fissure.Conclusion: The aim of the surgical procedure performed in this case was to divide the fissure between S1+2 and the inferior lobe to reduce the risk of an unexpected bronchial injury. 3D-CT helps surgeons to understand the stereoscopic positional relationships among anatomical structures.