A case 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

Perioperative QOL in lung cancer patients

Objective : Patients with lung cancer generally undergo minimally invasive surgery, such as video-assisted thoracoscopic surgery (VATS). This study examined the changes in health conditions and symptoms of patients with lung cancer using the European Organization for Research and Treatment of Cancer-Quality of Life Questionnaire (EORTC QLQ) C-30 questionnaires after surgery. Methods : This was a longitudinal descriptive study. One hundred and three patients with lung cancer who underwent lung resection at Tokushima University Hospital between 2012 and 2021 were eligible. They completed EORTC QLQ-C30, QLQ-LC13, the Cancer Dyspnea scale (CDS), and pulmonary-ADL (P-ADL) before and 1, 3, and 6 months after surgery. Results : Regarding functional scale scores, impairments in physical and role functions persisted for 6 months after surgery. In symptom scale scores, fatigue, pain, dyspnea, and appetite loss continued for 6 months after surgery. In CDS, sense of effort, discomfort, and total dyspnea scale scores were elevated for 6 months after surgery. In P-ADL, most ADL were impaired 1 month after surgery, but recovered by 3 months. The dyspnea index of ADL was lower for 6 months after surgery. Conclusions : Impairments in health conditions and symptoms persisted for 6 months after surgery despite its minimally invasive nature

Long-term outcomes of SN idenitification

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

ICG fluorescence for lung metastasis of HCC

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

Hypervascularized bronchial arteries affect lung cancer surgery

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 <10 years (P=0.047) in the multivariable analysis. Conclusions: Bronchial artery diameter was the most important risk factor of intraoperative bleeding and prolonged operative time during VATS lobectomy

EXPRESSION OF GHRELIN SYSTEM CONSTITUENTS IN THYMIC EPITHELIAL TUMORS

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

GAD1 EXPRESSION AND DNA METHYLATION IN THYMIC EPITHELIAL TUMORS

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

マウスiPS細胞由来の気管支肺胞幹細胞は末梢気道上皮再生を促進する

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

CLE for visceral pleural invasion

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