Increased Lipogenesis Is Important for Hexavalent Chromium-Transformed Lung Cells and Xenograft Tumor Growth

Hexavalent chromium, Cr(VI), is a known carcinogen and environmental health concern. It has been established that reactive oxygen species, genomic instability, and DNA damage repair deficiency are important contributors to the Cr(VI)-induced carcinogenesis mechanism. However, some hallmarks of cancer remain under-researched regarding the mechanism behind Cr(VI)-induced carcinogenesis. Increased lipogenesis is important to carcinogenesis and tumorigenesis in multiple types of cancers, yet the role increased lipogenesis has in Cr(VI) carcinogenesis is unclear. We report here that Cr(VI)-induced transformation of three human lung cell lines (BEAS-2B, BEP2D, and WTHBF-6) resulted in increased lipogenesis (palmitic acid levels), and Cr(VI)-transformed cells had an increased expression of key lipogenesis proteins (ATP citrate lyase [ACLY], acetyl-CoA carboxylase [ACC1], and fatty acid synthase [FASN]). We also determined that the Cr(VI)-transformed cells did not exhibit an increase in fatty acid oxidation or lipid droplets compared to their passage-matched control cells. Additionally, we observed increases in ACLY, ACC1, and FASN in lung tumor tissue compared with normal-adjacent lung tissue (in chromate workers that died of chromate-induced tumors). Next, using a known FASN inhibitor (C75), we treated Cr(VI)-transformed BEAS-2B with this inhibitor and measured cell growth, FASN protein expression, and growth in soft agar. We observed that FASN inhibition results in a decreased protein expression, decreased cell growth, and the inhibition of colony growth in soft agar. Next, using shRNA to knock down the FASN protein in Cr(VI)-transformed BEAS-2B cells, we saw a decrease in FASN protein expression and a loss of the xenograft tumor development of Cr(VI)-transformed BEAS-2B cells. These results demonstrate that FASN is important for Cr(VI)-transformed cell growth and cancer properties. In conclusion, these data show that Cr(VI)-transformation in vitro caused an increase in lipogenesis, and that this increase is vital for Cr(VI)-transformed cells.

International Journal of Molecular Sciences


Early Prediction of Radiotherapeutic Effecacy in a Mouse Model of Non-Small Cell Lung Carcinoma Using 18F-FLT and 18F-FDG PET/CT

This study investigated the usefulness of [18F]-3'-deoxy-3'-fluorothymidine (18F-FLT) and [18F]-fluoro-2-deoxy-D-glucose (18F-FDG) positron emission tomography (PET)/computed tomography (CT) imaging for predicting the therapeutic efficacy of non-small cell lung cancer (NSCLC) irradiation at an early stage after radiation treatment. Mice were xenografted with the human lung adenocarcinoma line A549 or large cell lung cancer line FT821. Tumour uptake of 18F-FLT and 18F-FDG was imaged using PET/CT before and 1 week after irradiation. In A549 tumours, 18F-FLT uptake was significantly decreased, and 18F-FDG uptake was unchanged post-irradiation compared with pre-irradiation. In FT821 tumours, uptake of both 18F-FLT and 18F-FDG uptake was substantially decreased post-irradiation compared with pre-irradiation. In both xenografts, tumour volumes in the irradiated groups were significantly decreased compared with those in the control group. 18F-FLT is expected to contribute to individual NSCLC therapy because it accurately evaluates the decrease in tumour activity that cannot be captured by 18F-FDG. 18F-FDG may be useful for evaluating surviving cells without being affected by the inflammatory reaction at an extremely early stage, approximately 1 week after irradiation. Combined use of 18F-FLT and 18F-FDG PET/CT imaging may increase the accurate prediction of radiotherapy efficacy, which may lead to improved patient outcomes and minimally invasive personalised therapy. J. Med. Invest. 70 : 361-368, August, 2023.

The Journal of Medical Investigation : JMI


Psychological Adjustment and Related Factors in Patients with Recurrence/Metastatic Lung Cancer after Curative Surgery

Background: Retinoblastoma (RB) occurs at a very young age. Since the disease is diagnosed at an early age, the family is responsible for the care of the child's disease acceptance. Objective: This study aims to explore the parenting process of children with RB toward disease acceptance. Methods: Eleven parents living in Japan were interviewed, and the data were analyzed using the Modified Grounded Theory Approach of Kinoshita (M-GTA). Results: There were twenty-one concepts representing the process of parenting a child with RB while guiding him or her toward disease acceptance, and nineteen of them were classified into ten categories based on semantic similarities. The two other concepts showed similar interpretability to categories. These categories and concepts were summarized into two core categories: ``Helping the child develop a positive mindset to define the disease as a part of him/herself'' and ``Paving the way in advance for the child to live comfortably when his or her living space expands''. Conclusions: In a cyclical framework of parenting, consisting of two core categories described in Results, the parents coordinated these two approaches while maintaining balance by ``Avoiding saying anything that does not need to be said'' and established their process of parenting a child with RB while guiding him or her toward disease acceptance, according to their household situation. The results suggest the necessity of recognizing that in childhood-onset cancers, such as RB, and diseases involving genetic issues, problems tend to occur not only during the treatment period but also at the time of life events and providing support from a comprehensive perspective.


Self-evaluation of Nursing Practice for Elderly Cancer Patients with Dementia Receiving Treatment in Acute Care Hospitals and Factors Influencing It

急性期病院で治療を受ける認知症高齢がん患者に対する看護実践とその関連要因

The purpose of this study was to clarify the current status of nursing practice for elderly cancer patients with dementia receiving treatment in acute care hospitals and related factors An anonymous self-administered questionnaire survey was conducted from May to July 2021 involving 400 people with experience of providing nursing care for elderly cancer patients with dementia Factor analysis identified <considering situations where patients have difficulty in managing their own safety> and <making arrangements to help patients maintain ordinariness> as factors of self-evaluation of nursing practice for elderly cancer patients with dementia receiving treatment in acute care hospitals Such evaluation was influenced by <years of nursing experience> <years of providing nursing care for elderly cancer patients with dementia> <participation in study groups/training seminars on dementia> <knowledge of dementia> <status of nursing practice for dementia> and <ethical behavior>

急性期病院で治療を受ける認知症高齢がん患者に対する看護実践とその関連要因を明らかにすることを目的とした．2021年5月∼7月に認知症高齢がん患者の看護経験を有する400名に無記名自記式質問紙調査を行った．急性期病院で治療を受ける認知症高齢がん患者に対する看護実践を構成する因子は「患者が自分の状態の安全を管理できないところを配慮する」「患者の日常性を維持させていくための工夫をする」が生成された．重回帰分析の結果，急性期病院で治療を受ける認知症高齢がん患者に対する看護実践には，「看護師経験年数」「認知症高齢がん患者の看護経験年数」「認知症に関する勉強会・研修会参加」[認知症に関する知識状況]，[認知症看護実践]，[看護師としての倫理的行動力]が関連していた．


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.


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.


Resillience in cancer care : What should nurses do?

Cancer is a serious threat to human health worldwide. Attention to the quality of life (QoL) of cancer patients is increasingly recognized as an important component of and a fundamental task in cancer care. Recent studies illustrate that resilience is a key biological factor affecting cancer patients' health status and QoL. However, few studies have focused on resilience during medical procedures of cancer patients from the perspective of nursing. In this study, we summarize recent literature exploring the clinical significance of resilience in oncology nursing, propose strategies for cancer care to improve the QoL of patients through interventions on resilience, and focus on emerging theories in oncology nursing. In summary, this will emphasize the importance of resilience in oncology nursing and benefit the clinical practices that improve patients' QoL and reduce the social burden caused by cancer. J. Med. Invest. 70 : 1-6, February, 2023.


The purpose of study was to clarify the psychological adjustment and related factors in lung cancer patients with recurrence/metastasis after curative surgery. Forty-one with lung cancer who were informed of a recurrence/metastasis after curative surgery completed a questionnaire comprised of the Mental Adjustment to Cancer Scale (MAC), Psychological Adjustment scale for Cancer Survivors (PACS), and information pertaining to demographic variables. When healthcare providers intervene in patients with lung cancer that has recurred/metastasized after curative surgery, it is necessary to assess patients' psychological adjustment based on demographic information, such as age, sex, marital status, and employment status, and to provide effective support promptly. Factors associated with psychological adjustment with recurrent/metastatic lung cancer after curative surgery were 1) female, 2) having a job, 3) over 65 years of age, 4) having a spouse, and 5) advanced-stage cancer. There was no difference in psychological adjustment between treatment and the period from cancer incidence to recurrence/metastatic. J. Med. Invest. 70 : 200-207, February, 2023.


Epigenetic downregulation of O6-methylguanine-DNA methyltransferase contributes to chronic hexavalent chromium exposure-caused genotoxic effect and cell transformation

Hexavalent chromium [Cr(VI)] is a common environmental pollutant and chronic exposure to Cr(VI) causes lung cancer and other types of cancer in humans, although the mechanism of Cr(VI) carcinogenesis remains elusive. Cr(VI) has been considered as a genotoxic carcinogen, but accumulating evidence indicates that Cr(VI) also causes various epigenetic toxic effects that play important roles in Cr(VI) carcinogenesis. However, it is not clear how Cr(VI)-caused epigenetic dysregulations contributes to Cr(VI) carcinogenesis. This study investigates whether Cr(VI) epigenetic toxic effect has an impact on its genotoxic effect. It was found that chronic low dose of Cr(VI) exposure time-dependently down-regulates the expression of a critical DNA damage repair protein O-methylguanine-DNA methyltransferase (MGMT), leading to the increases of the levels of the highly mutagenic and carcinogenic DNA lesion O-methylguanine (O-MeG) in human bronchial epithelial BEAS-2B cells. Moreover, the levels of MGMT and O-MeG in chronic Cr(VI) exposure-caused human lung cancer tissues are also significantly lower and higher than that in the adjacent normal lung tissues, respectively. It was further determined that chronic low dose of Cr(VI) exposure-transformed BEAS-2B cells display impaired DNA damage repair capacity and a high sensitivity to the toxicity of the alkylating chemotherapeutic drug Temozolomide. In contrast, stably overexpressing MGMT in parental BEAS-2B cells reverses chronic low dose of Cr(VI) exposure-caused DNA damage repair deficiency and significantly reduces cell transformation by Cr(VI). Further mechanistical studies revealed that chronic low dose of Cr(VI) exposure down-regulates MGMT expression through epigenetic mechanisms by increasing DNA methylation and histone H3 repressive modifications. Taken together, these findings suggest that epigenetic down-regulation of a crucial DNA damage repair protein MGMT contributes significantly to the genotoxic effect and cell transformation caused by chronic low dose of Cr(VI) exposure.


Effect of Observing Surgery during Clinical Adult Nursing Practicum on Postoperative Nursing from the Perspective of Students

成人看護学実習において学生が捉えた手術見学実習体験の術後看護への影響

Aim:To clarify the effects of observing surgery during clinical adult nursing practicum on postoperative nursing from the perspective of students. Methods:Semi-structured interviews were conducted with10students in their third year at a nursing college. The obtained data were qualitatively and inductively analyzed. Results:When observing surgery for the patients they were caring for, the students were aware of[the importance of observing and assessment with the influence of surgery and anesthesia taken into account]. Subsequently, they performed[postoperative pain management based on findings from the observation of actual surgical settings], while providing various approaches, including[Approaches to the promotion of patients' awareness of the current situation in order to prevent postoperative confusion and to protect safety]. Through this process, they developed[a sense of responsibility for nursing care inspired by patients・families' coping behaviors]． Discussion:The experience of observing surgery during clinical training was suggested to help students develop practical insights for care to promote postoperative recovery and a sense of responsibility for nursing care inspired by patients・families' coping behaviors.


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.


Experience of a nurse with a dilemma of hope to recover of cancer patients who have stopped treatment

治療を中止したがん患者がもつ回復への希望に対してジレンマを抱えた看護師の体験

In this study, the authors clarified experience of nurses with the dilemma toward the wish for recovery of cancer patients who discontinued treatment. An interview survey was performed for 14 nurses who had ever care cancer patients who discontinued their treatment. Experience of nurses with the dilemma toward the wish for recovery of cancer patients who discontinued treatment consisted of the following categories ;[ I am not able to respond to the patient's wish though I want to],[There is difference how to spend the time remained between the patient and me],[I do not have a sufficient power to support the end of the patient's life],[I feel disconsolate being unable to realize the patient's wish for recover]and[I'm a nurse. I never run from my patients]. The nurses with dilemma had experience in facing nursing cares driven by the sense of responsibility as a nurse while holding pain in their heart. Ethical problems may be underlying in this experience, and the need of team work, not individual responses, has been suggested. Therefore, support to reveal experience of nurses in daily nursing care is needed.


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.


The Development of the Arm Fixation Method to Prevent Ipsilateral Shoulder Pain in Patients Undergoing Lung Resection

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. An experimental study design was used. 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. 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). 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.


Practical Approaches of Nurses Certified for Cancer Chemotherapy

がん化学療法看護のエキスパートナースが大切にしている実践

To clarify the practical approaches of nurses in cancer chemotherapy, semi-structured interviews were conducted with 10 nurses certified for cancer chemotherapy in Tokushima Prefecture. The interview data were classified into the following categories : [not neglecting any step, as failure is unacceptable], [accurately predicting the symptoms of chemotherapy, rather than simply waiting for patients to report them], [making efforts to fulfill patients' desire to live], [bearing a heavy responsibility for handling toxic drugs], and [playing a role in generalizing chemotherapy]. The results suggest that the practical approaches of nurses in cancer chemotherapy three features place importance on "achieving positive effects while minimizing risks", "not narrowing down the scope of life", and "reducing resistance to chemotherapy".


Nursing Students' Understanding of Orem's Power Components in Gerontological Nursing Clinical Practice

看護学生が理解する高齢者看護学実習におけるオレムのパワー構成要素

The purpose of this study was to analyze trends in nursing students' assessments of the 10 powers of self-care agency in Gerontological Nursing and to identify educational support for students. The subjects were the practice records of 66 third-year nursing students who completed Gerontological Nursing from September 2019 to February 2020. The results showed that they had a perspective of directing their attention to the patient's interest, will, motivation, and reasoning among 10 power items that all students were able to assess, and that they approached their care with a respectful attitude toward the patient's perceptions and intentions for self-care. In addition, it could be inferred that they understood self-care in terms of patients' behaviors and activities by appearance. Conversely, from the items that more than half of the students were unable to assess, it could be inferred that they were unable to assess how to apply self-care agency to the patient's prospect and lives in future.


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.


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.


Can Computed Tomography Differentiate Adenocarcinoma In Situ from Minimally Invasive Adenocarcinoma?

Given the subtle pathological signs of adenocarcinoma in situ (AIS) and minimally invasive adenocarcinoma (MIA), effective differentiation between the two entities is crucial. However, it is difficult to predict these conditions using preoperative computed tomography (CT) imaging. In this study, we investigated whether histological diagnosis of AIS and MIA using quantitative three-dimensional CT imaging analysis could be predicted. We retrospectively analyzed the images and histopathological findings of patients with lung cancer who were diagnosed with AIS or MIA between January 2017 and June 2018. We used Synapse Vincent (v. 4.3) (Fujifilm) software to analyze the CT attenuation values and performed a histogram analysis. There were 22 patients with AIS and 22 with MIA. The ground-glass nodule (GGN) rate was significantly higher in patients with AIS (p < 0.001), whereas the solid volume (p < 0.001) and solid rate (p = 0.001) were significantly higher in those with MIA. The mean (p = 0.002) and maximum (p = 0.025) CT values were significantly higher in patients with MIA. The 25th, 50th, 75th, and 97.5th percentiles (all p < 0.05) for the CT values were significantly higher in patients with MIA. We demonstrated that quantitative analysis of 3D-CT imaging data using software can help distinguish AIS from MIA. These analyses are useful for guiding decision-making in the surgical management of early lung cancer, as well as subsequent follow-up.


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


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


【最先端医療を支える解剖学】呼吸器外科における最先端手術手技とCAL(Clinical Anatomy Laboratory)

Recently, endoscopic surgery is the most common procedurein the field of thoracic surgery. The newestthoracic surgeryapproaches are the video-assisted thoracic surgery(VATS), the one-port video-assisted thoracic surgery, and the robotic surgery. The individual advantages and disadvantages of these procedures have been discussed. VATS covers a field of view of the surgical field from the leg to the head. The basic method in performing VATS is that the surgeon operates on the abdominal area of the patient and the assistant expands the surgical field from the patient's back. It is currently the standard surgical procedure. The advantage of one-port VATS is the one port itself and its cosmetic advantages and pain reduction. The advantage of robotic surgery is that it has a clear three-dimensional enlarged field of view and can be performed using the delicate moving robotic arm. However, a good surgical training system should be established for the familiarization of these procedures. The clinical anatomy laboratory is the most efficient surgical training in addition to dry and wet lab training. Our institution has fresh-frozen cadavers, which are rare in Japan. The participating thoracic surgeons underwent training for VATS lobectomy, subxiphoid extended thymectomy, and pleurectomy decortication. This training is beneficial for educational and clinical purposes. In the future, we must obtain consistent surgical education before and after graduation using fresh-frozen cadavers. At the same time, a good organ model for training is also necessary. The surgeon has to cooperate with anatomy doctors for the development of a good surgical organ model. For the development of future surgical medicine, surgical training programs should be implemented.


Thoracoscopic lobectomy for lung cancer with unilateral absence of pulmonary artery


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


The actual situation on how nursing students understand older patients using Orem's nursing theory in the Geriatric Nursing Training

高齢者看護学実習におけるオレム看護理論の活用による看護学生の高齢患者の理解の実態

The purpose of this study was to clarify how the students understand the older patients based on Orem's nursing theory in Geriatric Nursing Training. The participants were17nursing students in third grade. The interview was carried out using semi-structured interview with students for how they felt older patients. As a result, two categories were extracted ; [ they need limited care for deficient parts]and[they have toughness cultivated through their long life]. The students understood the older patients as having self-caring abilities and thought that limited care should be provided only for deficient parts of patients. Also, they understood older patients as having strength cultivated through their long life. It is necessary for teachers to assess the Self-care agency more severely for students to get hold of mature elements characteristic of older patients.


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.


Prognostic significance of GAD1 overexpression in patients with resected lung adenocarcinoma

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. 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. 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. 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.


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.


Evaluation of the components of mediastinal cystic lesions using imaging techniques

To identify and differentiate patients with mediastinal cysts from those with cystic tumors requiring surgery. 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 (T1SIratio), and T2 signal intensity ratio (T2SI-ratio), acquired from magnetic resonance imaging (MRI) ; and standardized maximum uptake value (SUVmax) fromF-fluorodeoxyglucose positron emission tomography/computed tomography (F-FDG PET/CT). Both groups were statistically compared. 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. SUVmax fromF-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. J. Med. Invest. 66 : 106-111, February, 2019.

The Journal of Medical Investigation : JMI


Noninvasive monitoring of cisplatin and erlotinib efficacy against lung cancer in orthotopic SCID mouse models by small animal FDGPET/CT and CT.

We established patient-like models of lung cancer metastasis by orthotopically implanting human non-small cell lung cancer cell lines into SCID mice. We evaluated the utilities of small-animal computed tomography (CT) and positron-emission tomography-computed tomography (PET/CT) in these models to non-invasively and repeatedly monitor the anticancer effects of cisplatin and erlotinib. We orthotopically implanted three non-small cell lung cancer cell lines, A549, FT821 and PC-9, into SCID mice. These mice were then divided into three groups: Control, cis-diamminedichloroplatinum (II) (CDDP) (7-mg/kg CDDP, single administration intraperitoneally), and erlotinib (25 mg/kg erlotinib/day, oral administration 5 days/week). After treatment initiation, we repeatedly performed PET/CT and CT measurements and assessed anticancer effects based on tumor volumes and FDG uptake. A549 tumors were not affected by CDDP or erlotinib. FT821 tumors were highly responsive to CDDP. PC-9 tumors, which have an epidermal growth factor receptor mutation, were highly responsive to erlotinib. Histological results and metastatic rates correlated with the anticancer effects shown by CT. In our orthotopic SCID mouse lung cancer models, 18FDG-PET/CT and CT imaging non-invasively and repeatedly monitored the efficacies of cisplatin and erlotinib against not only implanted tumors, but also mediastinal lymph node metastases.


Bone marrow-derived fibrocytes promote stem cell-like properties of lung cancer cells.

Cancer stem cells (CSCs) represent a minor population that have clonal tumor initiation and self-renewal capacity and are responsible for tumor initiation, metastasis, and therapeutic resistance. CSCs reside in niches, which are composed of diverse types of stromal cells and extracellular matrix components. These stromal cells regulate CSC-like properties by providing secreted factors or by physical contact. Fibrocytes are differentiated from bone marrow-derived CD14 monocytes and have features of both macrophages and fibroblasts. Accumulating evidence has suggested that stromal fibrocytes might promote cancer progression. However, the role of fibrocytes in the CSC niches has not been revealed. We herein report that human fibrocytes enhanced the CSC-like properties of lung cancer cells through secreted factors, including osteopontin, CC-chemokine ligand 18, and plasminogen activator inhibitor-1. The PIK3K/AKT pathway was critical for fibrocytes to mediate the CSC-like functions of lung cancer cells. In human lung cancer specimens, the number of tumor-infiltrated fibrocytes was correlated with high expression of CSC-associated protein in cancer cells. These results suggest that fibrocytes may be a novel cell population that regulates the CSC-like properties of lung cancer cells in the CSC niches.


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.


Upregulation of histone-lysine methyltransferases plays a causal role in hexavalent chromium-induced cancer stem cell-like property and cell transformation

While hexavalent chromium [Cr(VI)] is generally considered as a genotoxic environmental carcinogen, studies showed that Cr(VI) exposure also causes epigenetic changes. However, whether Cr(VI)-caused epigenetic dysregulations plays an important role in Cr(VI) carcinogenicity remain largely unknown. The aim of this study was to determine if chronic low dose Cr(VI) exposure causes epigenetic changes, the underlying mechanism and whether chronic low dose Cr(VI) exposure-caused epigenetic dysregulation contributes causally to Cr(VI)-induced cancer stem cell (CSC)-like property and cell transformation. Two immortalized human bronchial epithelial cell lines (BEAS-2B and 16HBE) were exposed to 0.25 μM of KCrO for 20 and 40 weeks to induce cell transformation, respectively. Cr(VI)-induced epigenetic changes were examined in Cr(VI)-transformed cells and Cr(VI) exposure-caused human lung cancer tissues. Pharmacological inhibitors and gene knockdown experiments were used to determine the role of epigenetic dysregulation in Cr(VI) carcinogenicity. We found that chronic Cr(VI) exposure causes epigenetic dysregulation as evidenced by the increased levels of histone H3 repressive methylation marks (H3K9me2 and H3K27me3) and the related histone-lysing methyltransferases (HMTases). Pharmacological inhibition or knockdown of HMTases reduces H3 repressive methylation marks and malignant phenotypes of Cr(VI)-transformed cells. Moreover, knockdown of HMTases in parental cells significantly reduces chronic Cr(VI) exposure-induced CSC-like property and cell transformation. Further mechanistic study revealed that knockdown of HMTases decreases Cr(VI) exposure-caused DNA damage. Our findings indicate that chronic Cr(VI) exposure increases H3 repressive methylation marks by increasing the related HMTases expression; and that increased expression of HMTases plays a causal role in Cr(VI)-induced CSC-like property and cell transformation.


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.


Ipsilateral shoulder pain in patients following lung resection in the decubitus position

Aims and objectives: To examine the frequency, influencing factors and clinical course of shoulder pain in patients following lung resection. Background: Thoracoscopes have been introduced in the surgical treatment of lung cancer and allow for less invasive surgery with a minimal incision. However, decubitus position-related shoulder pain on the operated side has not yet been investigated. Design: A longitudinal descriptive study. Methods: Patients who underwent lung resection in the decubitus position. Patients were interviewed 2 days before surgery and once daily for 5 days after surgery. Interview items included background data, the concomitant use of epidural anaesthesia, operative duration, the presence of preoperative shoulder stiffness (excluding shoulder pain), type of surgery and site of operation. The intensity of pain was approximately 5 on an 11-point numerical rating scale. Descriptive statistics on patient backgrounds were obtained using SPSS Statistics 22 for Windows. Results: Of the 74 patients who underwent lung resection in a decubitus position, 30 (40.5%) developed shoulder pain on the operated side. The highest rating occurred 1 day after surgery and decreased over time. The following two factors were found to influence shoulder pain on the operated side: operative duration (Z = 2.63; p = .01) and the presence of preoperative shoulder stiffness (excluding shoulder pain) (X2= 4.16; p = .04). Conclusions: This study demonstrated that approximately 40% of patients who underwent lung resection in the decubitus position developed shoulder pain. Relevance to clinical practice: The presence of postoperative shoulder pain was related to both the duration of the operation and to the presence of preoperative shoulder stiffness. Although the shoulder pain resolves within 4 days, it causes the patient additional discomfort and distress. Therefore, further research is needed on positioning for thoracotomy in order to investigate ways to reduce or eliminate this complication of lung surgery.


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.


Frequent silencing of the candidate tumor suppressor TRIM58 by promoter methylation in early-stage lung adenocarcinoma

In this study, we aimed to identify novel drivers that would be epigenetically altered through aberrant methylation in early-stage lung adenocarcinoma (LADC), regardless of the presence or absence of tobacco smoking-induced epigenetic field defects. Through genome-wide screening for aberrantly methylated CpG islands (CGIs) in 12 clinically uniform, stage-I LADC cases affecting six non-smokers and six smokers, we identified candidate tumor-suppressor genes (TSGs) inactivated by hypermethylation. Through systematic expression analyses of those candidates in panels of additional tumor samples and cell lines treated or not treated with 5-aza-deoxycitidine followed by validation analyses of cancer-specific silencing by CGI hypermethylation using a public database, we identified TRIM58 as the most prominent candidate for TSG. TRIM58 was robustly silenced by hypermethylation even in early-stage primary LADC, and the restoration of TRIM58 expression in LADC cell lines inhibited cell growth in vitro and in vivo in anchorage-dependent and -independent manners. Our findings suggest that aberrant inactivation of TRIM58 consequent to CGI hypermethylation might stimulate the early carcinogenesis of LADC regardless of smoking status; furthermore, TRIM58 methylation might be a possible early diagnostic and epigenetic therapeutic target in LADC.


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


A case of subcutaneous emphysema induced by a portable thoracic drainage system after pneumonectomy

A 62-year-old man was admitted to our hospital for squamous cell lung carcinoma. We performed video-assisted right pneumonectomy after the induction chemoradiation therapy. We used portable thoracic drainage systems: Thopaz® and 19-Fr blake drain®. The patient had a severe cough and showed progressive subcutaneous emphysema. Thopaz® showed little air leakage. We confirmed the absence of a fistula at the bronchial stump via bronchoscopy and the absence of air suction from outside the drainage tube. We removed the thoracic drain because we believed Thopaz® caused the subcutaneous emphysema, and the subcutaneous emphysema subsequently fully resolved.

Thopaz® regulates the mean intrathoracic pressure by supplying air to the thoracic cavity when there is an excessive negative intrathoracic pressure. The mechanism of the increased subcutaneous emphysema by Thopaz® was considered as follows: sudden elevation of the intrathoracic pressure caused by the cough moved intrathoracic air into the subcutaneous space, instead of the blake drain®. Thopaz® supplied air into the thoracic cavity to restore the excessive negative intrathoracic pressure. This cycle was repeated and the subcutaneous emphysema worsened.

症例は62歳男性．右肺扁平上皮癌にて術前放射線化学療法後に胸腔鏡補助下右肺全摘術(ND2a-2)を施行した．ポータブル型胸腔ドレナージ装置であるThopazⓇ(トパーズ)にblakeドレーンⓇをつなげて術後胸腔内ドレナージした．術後，咳嗽が多く認められ，皮下気腫が増加した．トパーズのエアリーク表示量はほぼ0 ml/分であった．気管支鏡で気管支断端瘻がないことを確認した．トパーズのドレナージトラブルと判断し，ドレーン抜去すると皮下気腫は軽快した．トパーズには胸腔内圧調節機能があり，胸腔内が過陰圧になるとバルブが開き空気を吸い込ませる機能がある．本症例では咳嗽による急激な胸腔内圧上昇時に胸腔内の空気が皮下に漏れ，その結果起こった胸腔内圧の低下を感知したトパーズ経由で胸腔内へ空気が流入するという機序を繰り返したと考えられた．

The Journal of the Japanese Association for Chest Surgery


A case of aplastic anemia after thymothymectomy

胸腺腫摘出術後発症した再生不良性貧血の1例

Thymoma often leads to complications such as autoimmune disease, and symptoms of autoimmune disease are sometimes observed in patients even after thymothymectomy. Here, we encountered a case of aplastic anemia after thymothymectomy. A 73-year-old woman was admitted to our hospital for the treatment of an anterior mediastinal tumor. We performed thymothymectomy by median sternotomy. Histopathological findings showed type B1 thymoma when classified according to the World Health Organization system, and stage I thymoma when classified according to the Masaoka system. Six months after the surgery, the patient had pneumonia, and her hemogram showed pancytopenia; however, it had been normal before surgery. Puncture of the bone marrow showed the presence of fatty marrow, a cell density of 10-20%, and a myeloid/erythroid ratio of more than five. The patient was diagnosed with a very severe grade of aplastic anemia. Cyclosporine and supportive therapy were administered. However, the patient died of multiple organ failure 4 months after the onset of aplastic anemia.

The occurrence of aplastic anemia after thymothymectomy is a very rare complication. However, this complication is likely to be fatal since the patient becomes immunocompromised. Therefore, it is important to be careful regarding not only the recurrence of thymoma in the patient, but also the occurrence of autoimmune disease during follow-up after thymothymectomy.

胸腺腫には自己免疫性疾患が合併しやすく，時に胸腺腫摘出後に症状が顕在化することがある．胸腺腫摘出後に再生不良性貧血を発症した症例を経験したので報告する．

73歳，女性．前縦隔腫瘍にて紹介され，胸骨正中切開で胸腺胸腺腫摘出術を施行した．正岡分類I期，WHO分類はB1であった．術後半年後，肺炎を発症した．術前には正常範囲内であった血液検査で，汎血球減少を認めた．骨髄穿刺にて骨髄の細胞密度は10∼20%，脂肪髄かつ骨髄球/赤芽球の比は5以上であった．Grade 5の再生不良性貧血と診断した．シクロスポリンAを中心とした加療を行ったが，発症4ヵ月後に多臓器不全にて永眠された．

胸腺腫摘出後の再生不良性貧血は非常に稀な病態であるが，易感染性となり致死的となりうる．胸腺腫摘出後の経過観察の際には再発のみならず，自己免疫疾患の合併にも注意を必要とする．


The International Association for the Study of Lung Cancer/the International Thymic Malignancies Interest Group proposal for the TNM staging systems for thymic epithelial tumors and large-scale retrospective data


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


Late-onset myasthenia gravis is predisposed to become generalized in the elderly


Tumor growth-inhibitory effect of an angiotensin-converting enzyme inhibitor (captopril) in a lung cancer xenograft model analyzed using 18F-FDG-PET/CT.

We administered an angiotensin-converting enzyme inhibitor (captopril) to mice implanted with a human lung adenocarcinoma epithelial cell line (A549 cells) and investigated the tumor growth-inhibitory effect of captopril from the viewpoint of glucose metabolism using (18)F-fluorodeoxyglucose ((18)F-FDG)-PET/CT. Subcutaneous implantation of A549 cells (1.9×10(6) cells) was carried out in the lower right flank of mice. Fifteen days after the transplantation of A549 cells, mice (six in each group) were treated with captopril (3.0 mg/mouse) or saline (1000 μl/mouse) for 5 days. We performed (18)F-FDG-PET/CT imaging of the mice before and after the treatment and evaluated the degree of (18)F-FDG accumulation in tumors. In both groups (the captopril-administrated and control groups), values for the metabolic tumor volume (MTV), maximum standardized uptake value, total lesion glycolysis, and tumor volume after treatment had a tendency to increase. However, tumor growth was suppressed in the captopril-administrated group compared with the control group. In terms of the growth rate, the MTV and tumor volume were significantly different (P<0.05). It was found that captopril exerted a potential tumor growth-inhibitory effect; this was because the captopril-administrated group showed low values of MTV, maximum standardized uptake value, total lesion glycolysis, and tumor volume in comparison with the control group.


Lung regeneration by fetal lung tissue implantation in a mouse pulmonary emphysema model

The mortality and morbidity of chronic obstructive pulmonary disease are high. However, no radical therapy has been developed to date. The purpose of this study was to evaluate whether fetal mouse lung tissue can grow and differentiate in the emphysematous lung. Fetal lung tissue from green fluorescent protein C57BL/6 mice at 16 days' gestation was used as donor material. Twelve-month-old pallid mice were used as recipients. Donor lungs were cut into small pieces and implanted into the recipient left lung by performing thoracotomy under anesthesia. The recipient mice were sacrificed at day 7, 14, and 28 after implantation and used for histological examination. Well-developed spontaneous pulmonary emphysema was seen in 12-month-old pallid mice. Smooth and continuous connection between implanted fetal lung tissue and recipient lung was recognized. Air space expansion and donor tissue differentiation were observed over time. We could clearly distinguish the border zones between injected tissue and native tissue by the green fluorescence of grafts. Fetal mouse lung fragments survived and differentiated in the emphysematous lung of pallid mice. Implantation of fetal lung tissue in pallid mice might lead to further lung regeneration research from the perspective of respiratory and exercise function. J. Med. Invest. 63: 182-186, August, 2016.

The Journal of Medical Investigation : JMI


難治性有瘻性膿胸に気管支塞栓術を併用した有茎大網充填術が有効であった1例

難治性有瘻性膿胸に気管支塞栓術を併用した有茎大網充填術が有効であった1例

The Journal of the Japan Society for Respiratory Endoscopy


急速に増大する巨大気腫性肺囊胞に対して囊胞内吸引後にEWSとフィブリン糊注入で軽快した1例


胸腔鏡下右上葉切除術の手術時間に影響する因子の検討

胸腔鏡下右上葉切除術の手術時間に影響する因子の検討

The Journal of the Japanese Association for Chest Surgery


Chest Wall Metastasis of Anaplastic Lymphoma Kinase-positive Lung Adenocarcinoma 22 Years After Lobectomy

肺葉切除22年後に胸壁転移を認めたALK融合遺伝子陽性肺癌の1例

Background. When a new tumor appears after a long period of remission following surgery for lung cancer, it is difficult to determine whether the tumor is a recurrence or a new tumor. We herein report a case of a chest wall tumor that developed 22 years after pulmonary lobectomy diagnosed by an anaplastic lymphoma kinase (ALK) gene mutation. Case. An 80-year-old man underwent left-lung upper lobectomy for lung adenocarcinoma (pT4N2M0 Stage III) 22 years prior. We treated him with adjuvant chemotherapy after the surgery and did not detect a recurrence for 10 years. However, we noticed a chest wall mass 22 years after the surgery and diagnosed it by a biopsy as adenocarcinoma. The new specimen was stained with anti-thyroid transcription factor-1 (TTF-1) and anti-ALK antibodies, and the pathological specimen from the first surgery was also stained with anti-ALK antibody. We therefore diagnosed the chest wall tumor as a recurrence of the lung adenocarcinoma. We treated him with crizotinib, and the tumor shrank. However, we stopped the treatment because of the development of drug-induced interstitial pneumonia. We switched him to a platinum combination regimen, and follow-up is ongoing. Conclusions. When a lesion is suspected to be a recurrence long after surgery, an examination of gene mutations, such as that of ALK, may be useful.

背景．肺癌術後に長期間無再発生存し，遠隔臓器に病変の出現を認めた場合，再発であるか新規病変であるのかを判断するのは困難である．今回われわれは肺葉切除の22年後に出現した胸壁腫瘍に対し，anaplastic lymphoma kinase(ALK)融合遺伝子を検索することにより肺癌の胸壁転移と診断した1例を経験したため，報告する．症例．80歳男性．58歳時に肺腺癌(pT4N2M0 Stage III)に対して左肺上葉切除術を施行した．術後補助化学療法を行い，10年間再発を認めず経過観察を終了した．術後22年目に前胸部の無痛性腫瘤が出現し，生検で腺癌の所見であった．TTF-1陽性，ALK融合遺伝子陽性から肺腺癌の転移が疑われ，初回手術の病理標本もALK融合遺伝子陽性であったことから，胸壁転移と診断した．Crizotinibにて治療し腫瘍は縮小したが，薬剤性間質性肺炎を発症し中止した．プラチナ併用レジメンに変更して加療し，現在も経過観察を継続している．結論．術後遠隔期に再発転移を疑う病変が出現した場合，病理組織診断に加えALK融合遺伝子などの遺伝子変異検索を行うことで診断に至る可能性がある．


Acute exacerbation of interstitial pneumonia after pulmonary resection for lung cancer : Analysis of two cases

発症予測が困難であった肺癌術後間質性肺炎急性増悪の2例

Acute exacerbation of interstitial pneumonia (IP) is one of the most severe and fatal postoperative complications in lung cancer patients underlying IP. We treated two patients suffered from acute exacerbation of IP after pulmonary resection for lung cancer. We analyzed their clinical findings. Thoracoscopic lobectomy with mediastinal lymph node dissection was performed in these cases. The patients were diagnosed with acute exacerbation 4 or 5 days after operation and treated with steroids. Both patients had not been diagnosed as IPs before surgery, however, IPs were diagnosed by retrospective analysis of pathological examination for the removal lungs. Chest CT before surgery showed an interstitial shadow in the lung field faintly in these cases. It should be considered that patients who show a faint interstitial shadow in chest CT could potentially cause an acute exacerbation of IP after lung cancer operation.


Nurse administrators and hospital directors' perspectives about nurses' abilities in performing specific medical practices in hospitals within Tokushima Prefecture

徳島県内の看護職員高度人材育成研修推進事業における特定行為に係る実態調査

The purpose of this survey was to determine nurse administrators and hospital directors' perspectives about nurses' abilities in performing specific medical practices in hospitals in Tokushima Prefecture. The nurse administrators and hospital directors of all hospitals (113 hospitals) in Tokushima Prefecture were invited to respond to a survey questionnaire by mail posted during the period between February and March of 2015. Responses were received from 46 nurse administrators (response rate, 41%) and 38 hospital directors (response rate, 34%). The obtained data were analyzed using descriptive statistics and the narrative descriptions summarized. Majority of responses from nurse administrators and hospital directors were accepting that nurses have responsibilities for administering medicines such as tranquilizers, anti-anxiety and anticonvulsant drugs. This result was not affected by the size of the hospital, in which fifty four percent (54%) of respondents were from hospitals with less than 100 beds. In Japan, only hospitals with 100 beds or more may have procedures involving highly invasive treatments. Because of this, many of the respondents answered ``not applicable'' to statements in the questionnaire which were related to invasive treatments. Recruitment of nurses, strategies to cope with accidents and education curriculum were important concerns of nurse administrators and hospital directors which remain to be answered in future investigations.


Utility of respiratory-gated small-animal PET/CT in the chronologic evaluation of an orthotopic lung cancer transplantation mouse model.

Our aim in this study was to clarify the effects of respiratory-gated PET in the evaluation of lung cancer according to the (18)F-FDG uptake in an orthotopic transplantation mouse model. We created such a model, and we performed PET/CT. The mice were divided into two groups according to tumor volume: a small-tumor group (<20 mm(3)) and a large-tumor group (>20 mm(3)). We reconstructed the following conditions based on list-mode data: non-gated (3D) images and gated (4D) images, divided based on the respiratory cycle (expiration phase, stable phase, and inspiration phase). We calculated the maximum standardized uptake values (SUVmax) in each phase. We used the % difference [= (4D SUVmax - 3D SUVmax)/3D PET SUVmax × 100 (%)] to evaluate the differences in the 4D SUVmax and 3D SUVmax. The 4D SUVmax values were significantly higher than the 3D SUVmax, regardless of the tumor size. The % difference for the small tumors was greater than that for the large tumors, and it was highest in the stable phase. We conclude that the SUVmax in the stable phase under respiratory-gated PET are the most reliable. The SUVmax observed under non-gated PET are considered to be more frequently underestimated in cases involving small tumors than in those involving large tumors. In the chronologic study evaluating the time course of tumor development, the size of the tumor is small in early stage, and respiratory-gated PET is effective in reducing the underestimation of such tumors caused by respiratory motion.


Thoracoscopic pericardial fenestration for effective long-term management of non-tuberculous mycobacterium pericarditis

The long-term consequences of non-tuberculous mycobacterium pericarditis with pericardial effusion after fenestration have not been described. We encountered a case of non-tuberculous mycobacterium pericarditis in a 59-year-old woman with an underlying collagenosis. Repeated drainage was required because of rapid reaccumulation of the effusion. To definitively control the effusion, pericardial fenestration was performed by video-assisted thoracoscopic surgery. Chest radiography performed 6 years postoperatively showed no accumulation of pericardial or pleural fluid. The patient required careful follow-up and, to date, the pulmonary non-tuberculous mycobacterium (NTM) infection has been successfully suppressed by continuous antibiotic therapy. Pericardial fenestration with antibiotic therapy was an appropriate treatment for recurrent effusion in this case of NTM pericarditis.

General Thoracic and Cardiovascular Surgery


人工呼吸器管理中の慢性有瘻性膿胸に対してEWSを用いた気管支充填術を施行した1例


胸腔鏡下気管支動脈結紮を施行した気管支動脈蔓状血管腫の1例

胸腔鏡下気管支動脈結紮を施行した気管支動脈蔓状血管腫の1例


肺癌の術中胸膜浸潤診断の正確性についての検討

肺癌の術中胸膜浸潤診断の正確性についての検討


Comprehensive evaluation of the response of genes to the administration of the antitumor drug S-1 using a low density array.

S-1 is a newly developed dihydropyrimidine dehydrogenase inhibitory fluoropyrimidine that exhibits high clinical efficacy against non-small cell lung cancers. To identify genes that may be associated with chemosensitivity to the antitumor drug S-1, we used a low density array representing 93 genes to analyze expression profiles in 4 orthotopically implanted lung cancers derived from human lung cancer cell lines (Lu99, Lu130, LC6 and A549). The tumor growth inhibition (TGI) rates of S-1 in orthotopically implanted tumors of the Lu99, Lu130, LC6 and A549 cell lines were 34.6, 37.5, 32.1 and 3.6%, respectively. The expression of the PRSS3, ABCC4, TXN, SHMT1 and CMPK genes was significantly promoted in the orthotopically implanted SCID mouse model of the 4 lung cancer cell lines by the administration of S-1, while the expression of the LMO7 and FOLH1 genes was significantly suppressed. The expression of the ABCC1, 2 and TST genes was negatively correlated with TGI. The expression of the TK1 and ERCC2 genes was positively correlated with TGI. The results of the present study suggest that the expression of the ABCC1, 2, TST, TK1 and ERCC2 genes is related to resistance to the antitumor drug S-1.


Holter ECG monitoring of sympathovagal fluctuation during bronchoscopy.

This study shows for the first time that Holter ECG monitoring during diagnostic bronchoscopy was associated with activation of cardiac sympathetic and withdrawal of cardiac parasympathetic regulation, which may contribute to the occurrence of cardiac events during bronchoscopic procedures. So, Holter ECG monitoring during bronchoscopic procedures may confer reduction in cardiovascular events.

Heart rate increased significantly after pre-medication compared with that before pre-medication and increased further during bronchoscopy. The coefficient of variation (CVRR ) values after pre-medication and during bronchoscopy were significantly higher than those before pre-medication (P = 0.031 and P = 0.041, respectively). The low frequency (LF) power decreased during bronchoscopy. LF powers obtained after bronchoscopy were significantly lower than those obtained before bronchoscopy (P < 0.041). The high-frequency (HF) power was found to be decreased during bronchoscopy. In particular, HF powers obtained after bronchoscopy were significantly lower than those obtained before bronchoscopy (P < 0.019). Although the LF/HF ratios increased after pre-medication, they decreased temporarily during the bronchoscope insertion.


Evaluation of Powered ECHELON FLEX for pulmonary lobectomy

肺葉切除における電動式自動縫合器の使用経験

Objective : It has been accepted to use staplers for open and video-assisted thoracic surgery, however there was a risk in stapling of the pulmonary vasculatures. A newly developed stapler, powered ECHELON FLEX (Ethicon) is an electrically-powered stapler. It may reduce tip movement during cutting and stapling, which results in reduction of the risk of trauma to surrounding tissue. The aim of this study was to evaluate powered ECHELON FLEX for pulmonary lobectomy. Methods : We reviewed 16 patients who underwent pulmonary lobectomy with powered ECHELON FLEX in our institution from December, 2013 to April, 2014. Results : There were 25 stapling for the pulmonary artery, 17 stapling for the pulmonary vein, 16 stapling for the bronchus, and 33 stapling for the pulmonary parenchyma. Though two case of oozing from the stamps of a pulmonary artery and pulmonary parenchyma, there were no serious complications related to use of the staplers. Conclusions : The powered ECHELON FLEX can be used for pulmonary lobectomy safely.


Setting of fees for robotic surgery for lung cancer not covered by insurance

肺癌ロボット手術の私費料金設定

In Japan, the only robot surgery covered by health insurance is prostatectomy. Robot surgery for pulmonary cancer has not been approved as advanced health care, and hospitals are required to set out-of-pocket fees for surgery on their own. We calculated the fee not covered by insurance to be 1.28million yen, taking into account expenses for : (1) the use of medical equipment, (2) maintenance, (3) labor costs, and (4) medical materials and drugs. Since the fees for surgery plus hospitalization are actually incurred by patients, whether or not the hospitalization fee should be included in out-of-pocket medical fees is decided by each health care institution. In any case, it is necessary to provide patients with a summary of medical fees prior to surgery. Hospitals are required to collect data on pulmonary robot surgical cases while operating the system with medical fees incurred by individual patients.


Triple assessment of sentinel lymph node metastasis in early breast cancer using preoperative CTLG, intraoperative fluorescence navigation and OSNA.

Use of CTLG and fluorescence navigation made performing SLNB with high accuracy possible in institutions that cannot use the radioisotope method. OSNA provided accurate intraoperative method, allowing for completion of axillary node dissection during surgery and avoidance of second surgical procedure in patients with positive SLNs, thereby reducing patient distress and, finally, saving hospital costs.

SLN were identified by preoperative CTLG and intraoperative SLNB with fluorescence navigation in all patients, the identification rate was 100 %. SLN metastases were detected as positive by OSNA in 9 patients (18 %), 4 were (++), 4 were (+) and 1 was (+I). SLN metastases were detected as positive by histopathology in 10 patients (20 %). The concordance rate between OSNA and permanent sections was 90 %. The negative predictive value of CTLG was 80 %.


特集:Sentinel node navigation surgery Ⅱ．各論 3．肺癌におけるsentinel node navigation surgery


Non-invasive monitoring of anticancer effects of cisplatin on lung cancer in an orthotopic SCID mouse model using [¹⁸F] FDG PET-CT.

Positron emission tomography-computed tomography (PET-CT) with [18F] fluorodeoxyglucose (FDG) has recently been applied for evaluating tumor response to anticancer therapy. The aim of the present study was to evaluate the utility of FDG PET-CT in monitoring non-invasively and repeatedly the inhibitory effect of cisplatin (CDDP) on an orthotopic lung cancer model. Validation of in vivo FDG uptake in human lung cancer Ma44-3 cell line in an orthotopic SCID mouse model was carried out. Next, we assessed the use of FDG PET-CT to monitor the response of orthotopic lung cancer to the anticancer effect of CDDP. SCID mice were divided into the CDDP group (7 mg/kg single dose intraperitoneally) and the control group. Tumor volume and maximal standardized uptake value (SUV max) were calculated for all mice. All mice were sacrificed for histopathologic analysis. Validation of FDG PET-CT showed that tumor volume and SUV max were significantly correlated with postmortem tumor length measured in specimens (P=0.023) and (P=0.012), respectively, and there was a significant correlation between SUV max and tumor volume (P=0.048). Response monitoring showed that significant growth inhibition by CDDP in the form of SUV max of the CDDP group was significantly lower than that of the control group on day 8 (P=0.02) and on day 13 (P=0.003). Tumor volume of the CDDP group was significantly lower than that of the control group on day 13 (P=0.03). The present study supports using FDG PET-CT in monitoring tumor progression and therapeutic response of lung cancer in an orthotopic model non‑invasively and repeatedly.


Methylation and expression profiles of MGMT gene in thymic epithelial tumors

A key challenge in diagnosis and treatment of thymic epithelial tumors (TET) is in improving our understanding of the genetic and epigenetic changes of these relatively rare tumors. Methylation specific PCR (MSP) and immunohistochemistry were applied to 66 TET to profile the methylation status of DNA repair gene O6-methylguanine DNA methyltransferase (MGMT) and its protein expression in TET to clarify the association between MGMT status and clinicopathological features, response to chemotherapy and overall survival. MGMT methylation was significantly more frequent in thymic carcinoma than in thymoma (17/23, 74% versus 13/44, 29%; P<0.001). Loss of expression of MGMT protein was significantly more frequent in thymic carcinoma than in thymoma (20/23, 87% versus 10/44, 23%; P<0.0001). There is a significant correlation between of MGMT methylation and loss of its protein expression (P<0.0003). MGMT methylation and loss of expression were significantly more frequent in advanced thymic epithelial tumors (III/IV) than in early tumors (I/II). MGMT methylation plays a soul role in development of TET, especially in thymic carcinoma. Therefore, translation of our results from basic molecular research to clinical practice may have important implication for considering MGMT methylation as a marker and a target of future therapies in TET.