Investigating the usefulness of functional assessment of the elderly for lung cancer patients undergoing surgical treatment

外科治療を受ける肺がん患者に対する高齢者機能評価の有用性の検討


Lung regeneration with rat fetal lung implantation and promotion of alveolar stem cell differentiation by corticosteroids

The lung is a difficult organ to regenerate, and the development of functional lungs has still not been achieved. In this study, we investigated lung regeneration using a rat fetal lung tissue-implanted model. This study aimed to evaluate the functioning of the implanted fetal lung tissue and investigate the graft differentiation and maturation mechanism, focusing on alveolar stem cells. Fetal lung tissue fragments were obtained from Lewis rats on day 17 and implanted into adult lungs. Animals were divided into the following three groups: group 1, injection into the adult left lung parenchyma; group 2, injection with post-caval lobectomy; and group 3, injection with post-caval lobectomy and corticosteroid administration. Computed tomography was performed on weeks 1, 2, 4, and 8. The presence of alveolar pore, CD31 expression, and bipotential progenitor cell (podoplanin+/surfactant protein C+) localization were histologically evaluated. MiRNA expression was comprehensively compared among the three groups. The grafts comprised type I and type II alveolar cells connected to the recipient lungs with alveolar pores and capillary networks in the interstitial tissue. The alveolar space was the largest and the computed tomography value was the lowest in the grafts of the corticosteroid-administered group. The number of bipotential progenitor cells was the lowest in the corticosteroid administration group on day 7. Moreover, microRNA-487-3p, 374-5p, and 20b-5p expression was changed by more than 2-fold between the post-caval lobectomy and corticosteroid administration groups. Implanted fetal lung tissues established airway and capillary communication with the recipient lungs, and corticosteroids accelerated their maturation by promoting the differentiation of progenitor cells. The study findings provide new insights into lung regeneration research.


Assessment of dyspnea, ADL, and QOL in the perioperative period in lung cancer patients treated with minimally invasive surgery

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. 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. 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. Impairments in health conditions and symptoms persisted for 6 months after surgery despite its minimally invasive nature. J. Med. Invest. 70 : 388-402, August, 2023.

The Journal of Medical Investigation : JMI


Aberrant methylation of dipeptidyl peptidaselike 6 as a potential prognostic biomarker for lung adenocarcinoma

We previously performed the genome-wide screening of aberrantly methylated CpG islands (CGIs) using the paired tumorous and non-tumorous tissues of 12 lung adenocarcinomas (LADC). In comparisons with paired normal lung tissues, dipeptidyl peptidase-like 6 () has been identified as the most significantly hypermethylated CGI in LADC. is a protein that modulates A-type potassium channels in the somatodendritic compartments of neurons, which play a role in synaptic plasticity. Previous studies have showed that is downregulated in cancers, such as acute myeloid leukemia and melanoma, but upregulated in colon cancer, which is attributed to hyper- and hypomethylation, respectively. The present study investigated the methylation and expression levels of and its prognostic value in patients with LADC. The DNA methylation and mRNA expression levels of in surgically resected LADC tissues were examined by bisulfite pyrosequencing and reverse transcription-quantitative PCR, respectively. The DNA methylation and mRNA expression levels of were both significantly higher in LADC tissues compared with in normal lung tissues (n=25; P<0.0001). Overall and disease-free survival rates were significantly higher in LADC with high mRNA expression levels compared with those with low levels. In conclusion, epigenetic alterations in were significantly higher in LADC tissues compared with in normal lung tissues, which may contribute to the malignant features and worse prognosis of these patients.


Cone-beam computed tomography-guided endobronchial ultrasound using an ultrathin bronchoscope for diagnosis of peripheral pulmonary lesions: a prospective pilot study

Multimodal transbronchial biopsy (TBB) may have improved diagnostic yield for peripheral pulmonary lesions suspected as lung cancer. Radial endobronchial ultrasound (R-EBUS) provides real-time imaging and confirmation of the location of the lesions. Cone-beam computed tomography (CBCT) can confirm that the forceps tip has reached the lesion before biopsy. Patients with peripheral pulmonary lesions and a positive computed tomography (CT) bronchus sign (based on slice thickness of 1 mm) were prospectively enrolled. An ultrathin bronchoscope (UTB) and R-EBUS probe were advanced to the target bronchus. Thereafter, forceps were advanced, and CBCT was performed. R-EBUS was performed for re-navigation, if possible. The obtained EBUS and CBCT images were classified into "within" (type 1), "adjacent to" (type 2), or "far from" (type 3), based on the probe or forceps tip. For 20 lesions, the diagnostic yield was 85%. The primary EBUS images were of types 1, 2, and 3 in 12, 6, and 2 cases, respectively. The primary CBCT images were of types 1, 2, and 3 in 12, 6, and 2 cases, respectively. Primary EBUS and CBCT image types were equivalent in 14 cases. Of the 12 cases with type 1 primary EBUS image, 9 cases had a type 1 primary CBCT image, while 3 cases exhibited positional misalignment of the forceps tip. Re-navigation was required in 8 cases with types 2 and 3 primary CBCT images. CBCT-guided TBB using an UTB and EBUS may enable real-time positioning guidance and better re-navigation in the diagnosis of peripheral pulmonary lesions.


Diversity of lymphatic flow in patients with lung cancer revealed by computed tomography lymphography

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. 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. 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). 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.

Interactive Cardiovascular and Thoracic Surgery


GHSR methylation-dependent expression of a variant ligand and receptor of the ghrelin system induces thymoma tumorigenesis

Our previous study reported that the DNA methylation of growth hormone secretagogue receptor () was significantly higher in thymoma or thymic carcinoma (TC) than in normal thymic tissue samples. Thymic epithelial tumors (TETs) with higher DNA methylation were associated with significantly worse prognosis than those with lower levels of DNA methylation. Diversified components of the ghrelin- 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 methylation in thymoma tissue samples. However, a relationship was not found between ghrelin, GHSR1a or GOAT expression (native forms) and 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 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.


Hypervascularized bronchial arteries as a risk factor for intraoperative bleeding and prolonged surgery

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. 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. 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%) <70% (P=0.012), squamous cell carcinoma (P=0.049), and a bronchial artery diameter >2.0 mm (P<0.001) in the unadjusted analysis, and a bronchial artery diameter >2.0 mm (P<0.001) in the multivariable analysis. Risk factors for an operative time >200 min were being male (P<0.001), a history of smoking (P=0.007), FEV1.0% <70% (P=0.011), squamous cell carcinoma (P=0.046), a bronchial artery diameter >2.0 mm (P<0.001), and experience of surgeon <10 years (P=0.011) in the unadjusted analysis, and being male (P=0.047), a bronchial artery diameter >2.0 mm (P=0.024), and experience of surgeon <10 years (P=0.047) in the multivariable analysis. Bronchial artery diameter was the most important risk factor of intraoperative bleeding and prolonged operative time during VATS lobectomy.


Diagnosis of visceral pleural invasion using confocal laser endomicroscopy during lung cancer surgery

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). 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. 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%. 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.


GAD1 expression and its methylation as indicators of malignant behavior 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 () was identified as the 4th significantly hypermethylated CpG island in TC compared with thymomas. catalyzes the production of γ-aminobutyric acid from L-glutamic acid. 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 were analyzed using reverse transcription-quantitative PCR and immunohistochemistry, respectively. The DNA methylation levels of were significantly higher in TC tissues than in the normal thymus and thymoma tissues, and methylation exhibited high sensitivity and specificity for discriminating between TC and thymoma. The mRNA and protein expression levels of were significantly higher in TC tissues than in thymomas. Patients with TET with high 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.


Endobronchial Ultrasound Improves the Diagnosis of the Tracheobronchial Invasion of Advanced Esophageal Cancer

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.


気管支鏡の破損を分析する

Background. Bronchoscopy is used in many procedures, such as endoscopic ultrasonography, tracheal stent placement, placement of Endobronchial Watanabe Spigots, and preoperative coil marking. However, bronchoscopy is a complicated procedure, and breakage can occur due to external forces. Bronchoscope breakage is associated with both adverse economic effects and patient-related consequences, since these devices are expensive and their breakage may increase the rates of complications and cause interruptions in examinations and treatments, if repairs are necessary. Purpose. We considered the causes of bronchoscope damage at our hospital in order to design future preventive measures and precautions. Method. We examined the bronchoscope type, their breakage status, and the repair costs for the 246 bronchoscopes in our department between January 2015 and November 2017. Result. A bronchoscope was damaged in 3 of the 246 cases, resulting in a damage rate of 1.2%. Damage to the bronchoscope occurred during yttrium-aluminium-garnet laser resection (n=2) because of thermal damage to the suction forceps port, during a right upper lobe biopsy (n=1) because of the forceps contacting the curved part, and during an endobronchial ultrasound lymph node biopsy because of damage to the tube caused by the puncture needle (n=1). Conclusion. All cases of breakage occurred secondary to technical factors owing to a lack of understanding of the structure of the bronchoscope and procedural instability. Bronchoscope damage increases expenses and procedural time while potentially reducing safety. The bronchoscopy procedure must be improved. Furthermore, practitioners should increase their understanding of the bronchoscope structure in order to prevent damage. Precautionary measures can be communicated through short lecture courses and education programs in order to increase practitioners' understanding of the internal structure of the bronchoscope and measures to increase procedural stability.

背景．気管支鏡は超音波内視鏡，ステント，気管支充填術，また当科においては，術前コイルマーキングなど，様々な手技に使用されている．同時に，気管支鏡操作も複雑になり，様々な外力がかかることで破損が起こりやすくなる．気管支鏡の故障は医療経済面での不利益のみならず，合併症発生の増加や，修理期間中の検査・治療が中断されることによる患者側の不利益につながる．目的．当院で経験した気管支鏡の破損について検討し，その原因について探求し，今後の予防策や注意点に関して検討する．方法．2015年1月から2017年11月において当科で気管支鏡検査を施行した246例のうち，気管支鏡修理状況について，気管支鏡の種類や破損原因，修理費などについて検討した．結果．246例中3例(4本)の破損を認め，破損率は1.2%であった．気管内レーザー焼灼術による破損の1例(2本)は，吸引鉗子口の先端の熱損傷による破損であった．生検による破損の1例は湾曲部の鉗子操作によるものであり，超音波気管支鏡の破損の1例は，穿刺針による湾曲部の損傷によるものであった．結論．全例が手技的な要因で発生しており，機器の構造の理解不足や手技の不安定さが原因であった．気管支鏡破損は，経済面や安全面，時間的損失に影響を及ぼす．破損を起こさないためには，手技の向上や気管支鏡構造の理解が必要である．我々が取り組む方策は，気管支鏡内部構造の特性の理解，安定した手技の取得に至る講習，教育を常に意識して実行することである．

The Journal of the Japan Society for Respiratory Endoscopy


Cone-beam computed tomography versus computed tomography-guided ultrathin bronchoscopic diagnosis for peripheral pulmonary lesions: A propensity score-matched analysis

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. 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. 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). CBCT-guided TBB had a better diagnostic yield and shorter examination time than did CT-guided TBB.


Classifying the destination of right top pulmonary vein in 31 clinical cases

Disruption in the flow of blood vessels is of great concern during thoracic surgery. Preoperative 3-dimensional computed tomography facilitates visualization of the exact location and course of blood vessels. The right posterior upper lobe segmental vein, known as the right top pulmonary vein (RTPV), is an anomalous vein beginning at the right upper lobe and running through the posterior surface of the intermediate bronchus. We clinically investigated 31 patients with RTPV who underwent lobectomy or total resection of the right lung in our hospital or related institutions. We classified the final destination of RTPV into four types. The RTPV flowed into the left atrium in 35.5% of cases, superior pulmonary vein in 9.7%, inferior pulmonary vein in 41.9%, and independently into V6 in 12.9%. An RTPV with a diameter ≥ 5 mm was considered a main drainage vein in S2. We should pay attention to the RTPV during right lung lobectomy.

General Thoracic and Cardiovascular Surgery


Evaluation of extended thymectomy approaches based on residual fat tissue

This study analysed the patterns of extraction ranges, characteristics, advantages and disadvantages of median sternotomy (MS) and subxiphoid (SX) approaches for extended thymectomy. This study included patients with anterior mediastinum tumour and myasthenia gravis who underwent extended thymectomy at our institution between 2015 and 2018. There were 5 MS and 6 SX extended thymectomy surgeries with the VINCENT software. On preoperative computed tomography, the thymus area and fat tissue surrounding the thymus, which were planned for extraction, were traced using VINCENT (Ver. 4.0). We then constructed three-dimensional images and calculated the volumes. Evaluation of the extended thymectomy approach based on the residual fat tissue was required to determine the area of extended thymectomy. No significant differences in operation time (min) [SX: 197.3 ± 34.0, MS: 206.6 ± 91.4, drainage duration (days), SX: 2.2 ± 1.0, MS: 2.2 ± 0.4, hospital stay (days), SX: 11.8 ± 1.2, MS: 13.4 ± 2.1, residual rate (%), SX: 29.9 ± 17.5, MS: 58.7 ± 18.0 (P = 0.0519)] were observed between the 2 groups. Bleeding was significantly lower for SX than for MS. The residual rate was lower for SX than for MS. Considering the amount of the residual fat tissue, the SX approach allows an adequate dissection area for extended thymectomy compared with the MS approach.

Interactive Cardiovascular and Thoracic Surgery


Lobectomy for lung cancer with a displaced left B1 + 2 and an anomalous pulmonary vein: a case report

A displaced left B 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. 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 B and hyperlobulation between S and S, while the interlobar fissure between S and S was completely fused. Three-dimensional computed tomography (3D-CT) revealed an anomalous V joining the left inferior pulmonary vein and a branch of the V running between S and S. 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 V and confirm the locations of B and B when dividing the fissure. The aim of the surgical procedure performed in this case was to divide the fissure between S 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.


Biomarkers predicting the response to chemotherapy and the prognosis in patients with esophageal squamous cell carcinoma.

The prognosis of patients with esophageal squamous cell carcinoma (ESCC) has been improved by multidisciplinary therapy with chemoradiotherapy and surgery, but it remains poor. Advanced stage, malignant potential, and chemo-resistance contribute to the poor prognosis. Here, we attempted to identify predictive factors of the response to chemotherapy and the prognosis of ESCC patients. We examined 51 ESCC patients who were treated with chemotherapy followed by radical surgery, and 23 patients who were treated with chemotherapy alone. We conducted quantitative reverse transcription-polymerase chain reaction gene expression analysis using RNA extracted from 74 tumor tissue samples collected before chemotherapy and 67 tumor tissue samples collected after chemotherapy, focusing on PIK3CA, AKT-1, mTOR, 4E-BP1, p70S6K, PD-L1, and PD-L2. The proportions of patients with high expressions of AKT-1 and PD-L1 before chemotherapy were significantly higher among the non-responders than among the responders (p = 0.034, p = 0.020, respectively). Multivariate analyses revealed that high PD-L1 expression before chemotherapy was associated with poor response to chemotherapy (odds ratio 2.998; 95% CI 1.043-8.619; p = 0.042) and high p70S6K expression before chemotherapy was a poor prognostic factor (hazard ratio 2.518; 95% CI 1.058-5.988; p = 0.037). In addition, the patients with high expression of PD-L1 and PD-L2 in the tumors after chemotherapy had significantly worse survival than those with low expression of these genes (p = 0.012, p = 0.007, respectively). These results demonstrated that PD-L1 and p70S6K in the primary ESCC tissues were related to a poor response to chemotherapy and poor prognosis, respectively.


Diagnosis of recurrence and follow-up using FDG-PET/CT for postoperative non-small-cell lung cancer patients

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 F-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.


Long-term outcomes of sentinel node identification using indocyanine green in patients with lung cancer


Bronchioalveolar stem cells derived from mouse-induced pluripotent stem cells promote airway epithelium regeneration

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. 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. 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. 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.


A case of long-term unchanged calcifying fibrous tumor

A calcifying fibrous tumor (CFT) is a rare benign tumor that may occur in any part of the body. We report the case of an asymptomatic 21-year-old woman with thoracic tumors. Chest computed tomography showed multiple masses in the left costophrenic angle. As we were unable to diagnose the tumor with a CT-guided needle biopsy, we performed a thoracoscopic biopsy. We found smooth multilobulated masses on the pleura and multiple small nodules around the main tumors. Partial resection of the tumor was performed by VATS. Histological examination revealed that the tumor had hypocellular fibrosclerotic tissue and distributed psammomatous calcifications with inflammatory infiltrates. Immunohistochemistry demonstrated that the spindle cells were partially positive for CD34 and CD99, but negative for anaplastic lymphoma kinase-1, smooth muscle actin, BCL-2, STAT6, and S-100 protein. The tumor was diagnosed as CFT. The patient's postoperative recovery was uneventful, and no progression of the lesions was observed during follow-up.


Use of a prognostic risk score that aggregates the FDG-PET/CT SUVmax, tumor size, and histologic group for predicting the prognosis of pStage I lung adenocarcinoma

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.

International Journal of Clinical Oncology


Noninvasive monitoring of paclitaxel and lenvatinib efficacy against anaplastic thyroid cancer in orthotopic SCID mouse models using smallanimal FDGPET/CT


DNA methylation of GHSR, GNG4, HOXD9 and SALL3 is a common epigenetic alteration in thymic carcinoma

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.


Chromate exposure induces DNA hypermethylation of the mismatch repair gene MLH1 in lung cancer

Hexavalent chromium is recognized as a human carcinogen. Our previous studies revealed that lung cancer (LC) in chromate-exposed workers (chromate LC) had molecular features of frequent microsatellite instability (MSI), repression of MLH1 level, and aberrant DNA methylation of several tumor-suppressor genes, including MLH1. In the present study, we quantitatively investigated MLH1-promoter methylation status using bisulfite pyrosequencing of paired tumorous/nontumorous tissues from chromate and nonchromate LCs to determine the effect of chromate exposure on MLH1-promoter methylation. The methylation level of MLH1 promoter was significantly higher in chromate LC tumors (P < .001) than nonchromate LC tumors and, among chromate LC, significantly higher in tumorous tissue than nontumorous tissue (P = .004). Moreover, the methylation level of MLH1 promoter in normal lung tissue tended to be higher in chromate LC than nonchromate LC (P = .062). In addition, LC with reduced levels of MLH1 showed significantly higher methylation levels of MLH1 promoter than LC exhibiting normal MLH1 levels (P = .019). Moreover, immunohistochemical analyses determined that levels of SUV39H1, an H3K9me2-related methyltransferase, were higher in chromate LC than nonchromate LC (P = .076). Furthermore, we evaluated three DNA double-strand break-repair genes (MRE11, RAD50, and DNA-PKcs) as possible targets of MSI by fragment-length polymorphism analysis, revealing the mutation frequency of RAD50 as significantly higher in chromate LC than nonchromate LC (P = .047). These results suggest that chromate exposure might induce MLH1 hypermethylation in LC as a mechanism of chromate-induced carcinogenesis.


Transbronchial Biopsy Using an Ultrathin Bronchoscope Guided by Cone-Beam Computed Tomography and Virtual Bronchoscopic Navigation in the Diagnosis of Pulmonary Nodules

Transbronchial biopsy is a safe diagnostic approach for patients with peripheral pulmonary lesions; however, the diagnostic yield is low. 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). 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. 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. Transbronchial biopsy using an ultrathin bronchoscope guided by CBCT and VBN showed a very high yield in the diagnosis of pulmonary nodules.


Indocyanine green fluorescence imaging for resection of pulmonary metastasis of hepatocellular carcinoma

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. 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. 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. 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.


A case of thoracoscopic medial basal segmentectomy

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. 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. 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. In patients with this pattern of pulmonary artery and bronchial anatomy, isolated S7 segmentectomy is a feasible treatment option.

International Journal of Surgery Case Reports


Selective lobar blockade for lung resection : A report of two cases

選択的肺葉ブロックを用いた肺切除の2例

There are cases in which one-lung ventilation is difficult due to contralateral lung resection or low lung function. Selective lobar blockade can improve oxygenation compared with one-lung ventilation and secure a good operative field by inducing partial collapse. We report two cases of lung resection involving selective lobar blockade. (Case1) An 80-year-old female had previously undergone right upper and middle lobectomy for multiple lung tumors. Surgery was scheduled to remove a 7‐mm ground glass opacity from the upper left lobe. Oral intubation was performed (inner diameter of intubation tube:8mm). Next, the left upper lobe bronchus was blocked with a7Fr Arndt blocker under bronchoscopy, and partial resection of the left upper lobe was conducted. (Case2) A 75-year-old male had previously undergone right upper lobectomy for pulmonary tuberculosis and had developed right chronic empyema. Surgery was scheduled to remove a 22-mm nodule from the left lingular segment. Oral intubation was performed(inner diameter of intubation tube:8．5mm). Next, the left lingual bronchus was blocked with a7Fr Arndt blocker under bronchoscopy. Left lingular segmentectomy was carried out under thoracoscopic assistance. Intraoperative oxygenation was maintained in both cases, and the release of the block due to hypoxemia was not required in either case.


A feasibility study of postoperative adjuvant chemotherapy with fluoropyrimidine S-1 in patients with stage II-IIIA non-small cell lung cancer.

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.

The Journal of Medical Investigation : JMI


A case of atypical type A thymoma with vascular invasion and lung metastasis

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.

General Thoracic and Cardiovascular Surgery


Frequent silencing of RASSF1A by DNA methylation in thymic neuroendocrine tumours

Aberrant methylation of promoter CpG islands (CGIs) of tumour suppressor genes is a common epigenetic mechanism underlying cancer pathogenesis. The methylation patterns of thymic tumours have not been studied in detail since such tumours are rare. Herein, we sought to identify genes that could serve as epigenetic targets for thymic neuroendocrine tumour (NET) therapy. Genome-wide screening for aberrantly methylated CGIs was performed in three NET samples, seven thymic carcinoma (TC) samples, and eight type-B3 thymoma samples. The methylation status of thymic epithelial tumours (TETs) samples was validated by pyrosequencing in a larger cohort. The expression status was analysed by quantitative polymerase chain reaction (PCR) and immunohistochemistry. We identified a CGI on a novel gene, RASSF1A, which was strongly hypermethylated in NET, but not in thymic carcinoma or B3 thymoma. RASSF1A was identified as a candidate gene statistically and bibliographically, as it showed frequent CGI hypermethylation in NET by genome-wide screening. Pyrosequencing confirmed significant hypermethylation of a RASSF1A CGI in NET. Low-grade NET tissue was more strongly methylated than high-grade NET. Quantitative PCR and immunohistochemical staining revealed that RASSF1A mRNA and protein expression levels were negatively regulated by DNA methylation. RASSF1A is a tumour suppressor gene epigenetically dysregulated in NET. Aberrant methylation of RASSF1A has been reported in various tumours, but this is the first report of RASSF1A hypermethylation in TETs. RASSF1A may represent an epigenetic therapeutic target in thymic NET.


Malignant Pleural Mesothelioma Presenting Refractory Pneumothorax Successfully Treated by Intrapleural Administration of Diluted Fibrin Glue : Report of a Case

悪性胸膜中皮腫に合併した難治性気胸に対し胸腔内フィブリン糊注入療法が有効であった1例

The Japanese Journal of Thoracic Surgery


CXCR4 Expression is Associated with Poor Prognosis in Patients with Esophageal Squamous Cell Carcinoma

Chemokines and their receptors are known to play important roles in the tumorigenesis of many malignancies. The chemokine CXCL12 and its receptors CXCR4 and CXCR7 were suggested to be involved in cancer invasion and metastasis. The aim of this retrospective study was to evaluate the prognostic impact of the expressions of CXCL12, CXCR4 and CXCR7 in patients with esophageal squamous cell carcinoma (ESCC). We used immunohistochemistry (IHC) and reverse transcriptase-polymerase chain reaction (RT-PCR) to evaluate the expressions of CXCL12, CXCR4, and CXCR7 in ESCC patients' tumor biopsy specimens obtained during preoperative endoscopy or surgery. These results were compared with the patients' clinicopathological parameters and survival. IHC was conducted for 172 patients. High expression of CXCR4 in the cytoplasm and nuclei and that of CXCR7 were associated with poor cause-specific survival (CSS) (P= .002 and .010, respectively). The specimens from 52 of the 172 patients were examined by RT-PCR and quantitative real-time PCR. The expression levels of messenger RNA (mRNA) of CXCR4 and CXCR7 were significantly increased in the tumors compared with normal esophageal mucosae (P < .0001). The expression level of mRNA of CXCR4 was associated with poor recurrence-free survival and CSS (P = .012 and .038, respectively). CXCR4 expression is associated with poor prognosis in patients with ESCC.


Autofluorescence for the diagnosis of visceral pleural invasion in non-small-cell lung cancer

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. 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. 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. 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.

European Journal of Cardio-Thoracic Surgery


肺癌手術における周術期口腔機能管理の術後肺炎予防効果

肺癌手術における周術期口腔機能管理の術後肺炎予防効果

The Journal of the Japanese Association for Chest Surgery


Surgical resection after BEP therapy induced interstitial pneumonia during treatment for primary mediastinal malignant germ cell tumor

縦隔原発悪性胚細胞性腫瘍に対するBEP療法中に発症した間質性肺炎治療後に手術を施行した2例

The incidence of interstitial pneumonia caused by bleomycin is increasing, dependent on the total dose. Care should be taken in the treatment of a germ cell tumor requiring high-dose administration. If interstitial pneumonia occurs during treatment for a primary mediastinal malignant germ cell tumor, it may influence the subsequent surgical treatment. We report two surgical cases of interstitial pneumonia that occurred during BEP (bleomycin+etoposide+cisplatin) therapy for a primary mediastinal malignant germ cell tumor. Case 1 was a 19-year-old man and case 2 was a 24-year-old man. They both had an anterior mediastinal tumor of around 10 cm in diameter that was diagnosed as a yolk sac tumor by needle biopsy, and received BEP therapy. Interstitial pneumonia occurred at total bleomycin doses of 360 and 330 mg, respectively. They received steroid pulse treatment 103 and 109 days after starting therapy, respectively. Thereafter, they received steroid maintenance treatment by oral administration. Because they showed the improvement of interstitial pneumonia on imaging examinations, they received residual tumor resection and partial resection of the lung 17 and 26 days after starting steroid pulse treatment, respectively. Both post-operative courses were good, without the onset of respiratory failure.

ブレオマイシンによる間質性肺炎は総投与量依存性に頻度が増加する．高容量投与が必要となる縦隔胚細胞性腫瘍において，治療中に間質性肺炎を生じた場合は，その後の手術にも影響がおよぶ可能性がある．今回BEP(bleomycin+etoposide+cisplatin)療法中に生じた間質性肺炎を治療し，早期に手術を施行した2例を報告する．症例1は19歳の男性，症例2は24歳男性で，ともに前縦隔に約10 cmの腫瘍を認め，針生検で卵黄囊腫瘍と診断された．BEP療法を開始し，それぞれ，ブレオマイシン総投与量360，330 mgで間質性肺炎を発症した．化学療法開始103日目，109日目から3日間のステロイドパルスを行い，その後内服で維持療法を行った．画像上，間質性肺炎の改善を認めたため，手術はパルス療法開始後17日目と26日目に残存腫瘍切除と肺部分切除を行った．ともに術後呼吸不全の発症なく経過良好であった．


A case report of perivascular epithelioid cell tumor of the lung: A benign tumor with intense FDG uptake

FDG-PET/CT陽性を示した肺原発良性血管周囲類上皮細胞腫瘍の1例

The patient was a 36-year-old who was undergoing follow-up observation after a mediastinal mass was identified during a physical examination at a local clinic 3 years earlier. Over time, the mass showed a tendency to grow, and so the subject consulted our hospital for close examination and treatment. Chest CT revealed a mass shadow of 36 mm in the left middle mediastinum, and FDG-PET/CT revealed FDG uptake with an SUVmax of 4.93 at the same site. On suspicion of a mediastinal tumor such as a thymoma, video-assisted thoracoscopic surgery was performed; however, the lesion was a sessile intrapulmonary tumor. Rapid pathological diagnosis revealed low-grade malignancy, and left upper segmentectomy was performed. The postoperative pathology results led to the diagnosis of a benign perivascular epithelioid cell tumor (PEComa). PEComa is a rare condition, for which there are very few reports using PET/CT. We report a case of benign PEComa that showed elevated FDG uptake.

症例は36歳女性．3年前より近医の検診で縦隔腫瘤が疑われ，経過観察を行っていた．継時的に増大傾向を示し，精査加療目的に当院受診となった．胸部CTで左中縦隔に36 mmの腫瘤影を認め，FDG-PET/CTにて同部位にSUVmax 4.93の集積を認めた．胸腺腫などの縦隔腫瘍を疑い胸腔鏡下手術を施行したが，病変は広基性な肺内腫瘍であった．迅速病理にて低悪性度腫瘍の結果であり左肺上大区切除を行った．術後の病理結果より良性血管周囲類上皮細胞腫瘍(benign perivascular epithelioid cell tumor:PEComa)と診断した．PEComaはまれな疾患であり，PET/CTを使用した報告は極めて少ない．FDGの集積亢進を認めた良性PEComaの1例を報告する．


Indocyanine Green Fluorescence Intraoperative Imaging for Hepatic Hydrothorax With a Small Diaphragmatic Defect

Seminars in Thoracic and Cardiovascular Surgery


Indocyanine Green Fluorescence Navigation Thoracoscopic Metastasectomy for Pulmonary Metastasis of Hepatocellular Carcinoma

Indocyanine green can selectively accumulate in primary hepatocellular carcinoma (HCC) and extrahepatic metastases. We report a patient who underwent resection of pulmonary metastasis of HCC using a thoracoscopic near-infrared imaging system and fluorescent navigation surgery. A 66-year-old man with suspicion of pulmonary metastasis of HCC was referred to our hospital. Indocyanine green was injected intravenously at a dose of 0.5 mg/kg body weight, 20 h before thoracoscopic surgery. An endoscopic indocyanine green near-infrared fluorescence imaging system showed clear blue fluorescence, indicating pulmonary metastasis of HCC in a lingular segment. We performed wide wedge resection using the fluorescence image for navigation to confirm the surgical margins. The specimen was histologically confirmed as a pulmonary metastasis of HCC. In conclusion, thoracoscopic indocyanine green near-infrared fluorescence imaging for pulmonary metastases of HCC is useful in identifying tumor locations and ensuring resection margins.

Annals of Thoracic and Cardiovascular Surgery


Current Status and Effectiveness of Perioperative Oral Health Care Management for Lung Cancer and Esophageal Cancer Patients

肺癌・食道癌の周術期における口腔ケアの現状とその効果

The Japanese Journal of Thoracic Surgery