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

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


Effectiveness of surveillance by echocardiography for Cancer therapeutics-related cardiac dysfunction of patients with breast Cancer

Cancer therapeutics-related cardiac dysfunction (CTRCD) affect the prognosis of patients with breast cancer. Echocardiographic surveillance of patients treated with anti-human epidermal growth factor receptor type 2 (HER2) antibodies has been recommended, but few reports have provided evidence on patients with breast cancer only. We aimed to evaluate the effectiveness of echocardiographic surveillance for breast cancer patients. We identified 250 patients with breast cancer who were treated with anti-HER2 antibodies from July 2007 to September 2021. We divided 48 patients with echocardiographic surveillance every 3 months into the surveillance group and 202 patients without echocardiographic surveillance into the non-surveillance group. In the surveillance group, patients with a considerable reduction in global longitudinal strain of 15 % were considered for the initiation of cardioprotective drugs. The composite outcome of CTRCD and acute heart failure was the study endpoint. The mean age was 59 ± 12 years. During the follow-up period of 15 months (12-17 months), 12 patients reached the endpoint. The surveillance group had significantly lower incidence of the composite outcome (2.1 % vs. 5.5 %, adjusted odds ratio: 0.28, 95 % confidential intervals: 0.09-0.94; p = 0.039) and higher rates of prescriptions of cardioprotective drugs than the non-surveillance group. The incidence of cardiac complications was significantly lower in the surveillance group than the non-surveillance group, which supports the effectiveness of echocardiographic surveillance in patients with breast cancer.


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

Patients with lung cancer generally undergo minimally invasive surgery, such as video-assisted thoracoscopic surgery (VATS). This study examined the changes in health conditions and symptoms of patients with lung cancer using the European Organization for Research and Treatment of Cancer-Quality of Life Questionnaire (EORTC QLQ) C-30 questionnaires after surgery. This was a longitudinal descriptive study. One hundred and three patients with lung cancer who underwent lung resection at Tokushima University Hospital between 2012 and 2021 were eligible. They completed EORTC QLQ-C30, QLQ-LC13, the Cancer Dyspnea scale (CDS), and pulmonary-ADL (P-ADL) before and 1, 3, and 6 months after surgery. Regarding functional scale scores, impairments in physical and role functions persisted for 6 months after surgery. In symptom scale scores, fatigue, pain, dyspnea, and appetite loss continued for 6 months after surgery. In CDS, sense of effort, discomfort, and total dyspnea scale scores were elevated for 6 months after surgery. In P-ADL, most ADL were impaired 1 month after surgery, but recovered by 3 months. The dyspnea index of ADL was lower for 6 months after surgery. Impairments in health conditions and symptoms persisted for 6 months after surgery despite its minimally invasive nature. J. Med. Invest. 70 : 388-402, August, 2023.

The Journal of Medical Investigation : JMI


Absolute Lymphocyte Count Changes During Neoadjuvant Chemotherapy are Associated With Prognosis of Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer Patients

Some reports have shown that absolute lymphocyte count (ALC) is associated with prognosis in breast cancer; however, the impact of ALC changes remains unclear. This study aimed to investigate the relationship between ALC changes during neoadjuvant chemotherapy for human epidermal growth factor receptor-2 (HER2)-positive breast cancer patients and disease prognosis. This retrospective cohort study January 2010 to September 2020) included patients diagnosed with HER2-positive breast cancer and treated with trastuzumab-based neoadjuvant chemotherapy. The ALC ratio was defined as the ALC value after administration of the anti-HER2 drug divided by the ALC value before administration. The optimal ALC ratio cut-off value was identified using the receiver operating characteristic curve analysis and Youden's index. The relationship between the ALC ratio and disease-free survival was assessed using the Kaplan-Meier method. Univariate and multivariate analyses were performed using the Cox proportional hazards model. Data from a total of 100 HER2-positive breast cancer patients were analyzed. The cut-off value of the ALC ratio was set as 1.142. The median follow-up period was 52.0 (range: 5.1-123.7) months. The 5-year disease-free survival rates were 88.4% and 60.9% in the high-and low-ALC ratio groups, respectively, and were significantly higher in the high-ALC ratio group (p = .0031). The ALC ratio was an independent prognostic factor in multivariate Cox proportional hazards analysis (p = .0032). HER2-positive breast cancer patients with a higher ALC ratio during trastuzumab-based neoadjuvant chemotherapy may have a better prognosis than their counterparts.


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.


Abscopal effect in a patient with solitary extramedullary plasmacytoma of the thyroid: case report

The abscopal effect is a systemic antitumor response that occurs distant to the irradiation site and is induced by local irradiation. We herein describe a case of solitary extramedullary plasmacytoma (SEP) of the thyroid in which bone metastases disappeared after thyroidectomy and cervical radiotherapy (RT). A 68-year-old man with a right cervical swelling for approximately 10 years visited a hospital with left elbow pain that persisted for 5 months. He was referred to our hospital for more detailed examinations and treatment. An immobile mass of approximately 10 cm in diameter was palpable on the right side of the patient's neck. Computed tomography (CT) showed osteolytic changes in the left humerus and right scapula, and a tumor in the right lobe of the thyroid gland. The patient was diagnosed with widely invasive follicular carcinoma and multiple bone metastases and underwent total thyroidectomy. During surgery, tumor infiltration into the trachea was observed. Shaving between the tumor and trachea was performed. Based on the results of a pathological examination, the patient was diagnosed with primary extramedullary plasmacytoma of the thyroid. After surgery, external beam RT was performed on the neck, which also reduced the pain in the left elbow. Positron emission tomography (PET)-CT showed the decreased accumulation of fluorodeoxyglucose (FDG) in the left humerus and right scapula, and the amelioration of osteolytic changes on CT. SEP of the thyroid is rare, and to the best of our knowledge, this is the first case report in which the abscopal effect was observed after thyroidectomy and cervical RT.


F-FDG PET/CT Showing Rare Mediastinal Growing Teratoma Syndrome Following Chemotherapy.

Molecular Imaging and Radionuclide Therapy


A case of papillary thyroid carcinoma with renal and pulmonary metastases

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


Axillary lymphangioma that developed following COVID-19 vaccination: a case report

Extensive vaccination programs are being implemented worldwide for coronavirus disease 2019 (COVID-19). With the spread of vaccination, swelling of the lymph nodes after vaccination is frequently seen. We encountered a patient who developed left axillary lymphadenoma following vaccine administration. The patient was a Japanese woman in her 80 s who had previously undergone surgery for right breast cancer. She received two injections of the Pfizer-BioNTech COVID-19 vaccine in her left arm. Approximately 3 months later, she complained of left axillary swelling, and imaging resulted in a diagnosis of left axillary lymphangioma. In accordance with the patient's wishes, we performed axillary mass resection. The pathological diagnosis was lymphangioma. Our examination findings indicated that congestion of the axillary lymph vessels might have been caused by upper-arm injections of the COVID-19 vaccine.


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


XB130 deficiency causes congenital hypothyroidism in mice due to disorganized apical membrane structure and function of thyrocytes

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


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.


HER2陽性乳癌患者における術前化学療法開始前の総リンパ球数は予後予測の指標となり得る

Purpose : Several studies have shown that peripheral hematologic parameters, such as the absolute lymphocyte count(ALC)and neutrophil to lymphocyte ratio(NLR)can predict the prognosis for malignant tumor. We investigated the relation of these parameter and prognosis before neoadjuvant chemotherapy for human epidermal growth factor receptor-2(HER2)-positive breast cancer patients. Methods : From April 2009 to March 2019, 85 patients diagnosed with HER2‐positive breast cancer and treated with trastuzumab-based neoadjuvant chemotherapy were included in this retrospective cohort study. The optimal cut-off for the NLR and ALC was identified using the receiver operating characteristic(ROC)curve analysis and Youden's index. Results : The median age of patients at the start of treatment was 58．9(range 32‐81)years. The median follow-up time for HER2-positive breast cancer patients was 52．0(range:9．8‐114．3)months. In this period, 11 patients developed recurrence. The low-ALC group showed better disease free survival than the high-ALC group(p=0．0482). There was no significant difference in disease free survival between the low- and high-NLR groups. Conclusion : ALC before neoadjuvant chemotherapy may be a predictor of prolonged disease free survival in HER2‐positive breast cancer patients.


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

The present study investigated whether highly vascularized bronchial arteries affect the intraoperative blood loss and the operative time of video-assisted thoracic surgery (VATS) lobectomy for patients with non-small cell lung cancer. We retrospectively collected data on consecutive pathological stage I to IIIA non-small cell lung cancer patients who underwent VATS lobectomy with systematic lymph node dissection between January 2017 and December 2019. Patients were divided into the following two groups according to bronchial artery diameters on preoperative enhanced contrast computed tomography (CT) findings: ≤2 and >2 mm groups. Among the 175 patients enrolled, risk factors for intraoperative blood loss >50 mL were being male (P=0.005), a history of smoking (P=0.01), percent forced expiratory volume in 1 s (FEV1.0%) <70% (P=0.012), squamous cell carcinoma (P=0.049), and a bronchial artery diameter >2.0 mm (P<0.001) in the unadjusted analysis, and a bronchial artery diameter >2.0 mm (P<0.001) in the multivariable analysis. Risk factors for an operative time >200 min were being male (P<0.001), a history of smoking (P=0.007), FEV1.0% <70% (P=0.011), squamous cell carcinoma (P=0.046), a bronchial artery diameter >2.0 mm (P<0.001), and experience of surgeon <10 years (P=0.011) in the unadjusted analysis, and being male (P=0.047), a bronchial artery diameter >2.0 mm (P=0.024), and experience of surgeon <10 years (P=0.047) in the multivariable analysis. Bronchial artery diameter was the most important risk factor of intraoperative bleeding and prolonged operative time during VATS lobectomy.


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

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


GAD1 expression and its methylation as indicators of malignant behavior in thymic epithelial tumors

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


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

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


気管支鏡の破損を分析する

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

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

The Journal of the Japan Society for Respiratory Endoscopy


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

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


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

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

General Thoracic and Cardiovascular Surgery


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


Comprehensive Interventions for Building a Better Regional Cooperation for Cancer Patients

より良いがんの地域連携体制構築のための包括的な取り組み

Objectives : We introduce our comprehensive interventions for building a better regional cooperation for cancer patients. Methods : We have made a questionnaire survey for community physicians asking whether they can accept cancer patients and what types of medical treatments they can provide. Based on the questionnaire responses, we visualized the information, developed a new critical pathway, and improved the system in a basic hospital. Results : We first organized the information obtained from the questionnaire responses and uploaded the organized information to the basic hospital's homepage for public access. We then developed a new critical pathway for the cooperation among community physicians considering the prophylactic administration of a granulocyte-colony stimulating factor (G-CSF) formulation for treating cancer patients. This treatment was subsequently applied to four patients. Additionally, a community physician was matched with each patient by a medical social worker during the patients' hospitalization. We improved the basic hospital's simple electronic medical record system to reduce the physicians' workloads. As a result, the document creation could be completed within one minute, and so they could relate to approximately 10 times larger number of cases. Conclusions : Satisfactory cancer treatments can be provided for patients by building the better regional cooperative relationships and dividing the roles with community physicians in an earlier time.

目的:より良いがんの地域連携体制を構築するための包括的な取り組みについて紹介する．方法:かかりつけ医を対象に行った，がん患者の連携の可否と役割分担できる診療内容に関するアンケート結果をもとに，情報の可視化，新たな連携クリティカルパス(連携パス)の導入，拠点病院内の環境整備を行った．結果:まず，アンケート結果の情報を整理し，誰もがアクセスできるよう病院ホームページにアップして可視化した．さらに，予防的G-CSF(Granulocyte-Colony Stimulating Factor)投与連携パスを運用し，少数だが4例に適用した．加えて，入院中に医療ソーシャルワーカーが介入してかかりつけ医を決定し，文書作成を1分以内に完遂できる簡便な電子カルテ運用にして医師の作業負担を減らし，連携件数を約10倍増加させた．結語:より早期から緊密に情報交換し，役割分担することで，患者にとって満足度の高いがん医療を提供できる．今回の取り組みは，より良い連携体制構築に寄与すると考える．


Japanese Journal of Cancer and Chemotherapy


Relationship between regional left ventricular dysfunction and cancer-therapy-related cardiac dysfunction

The aim of our study was to assess the association between risk of cancer-therapy-related cardiac dysfunction (CTRCD) after first follow-up and the difference in echocardiographic measures from baseline to follow-up. We retrospectively enrolled 87 consecutive patients (58±14 years, 55 women) who received anthracycline and underwent echocardiographic examinations both before (baseline) and after initial anthracycline administration (first follow-up). We measured absolute values of global longitudinal strain (GLS), apical longitudinal strain (LS), mid-LS and basal-LS at baseline and first follow-up, and per cent changes (Δ) of these parameters were calculated. Among 61 patients who underwent further echocardiographic examinations (second follow-up, third follow-up, etc), we assessed the association between regional left ventricular (LV) systolic dysfunction from baseline to follow-up and development of CTRCD, defined as LV ejection fraction (LVEF) under 53% and more absolute decrease of 10% from baseline, after first follow-up. LVEF (65%±4% vs 63±4%, p=0.004), GLS (23.2%±2.6% vs 22.2±2.4%, p=0.005) and basal-LS (21.9%±2.5% vs 19.9±2.4%, p<0.001) at first follow-up significantly decreased compared with baseline. Among the 61 patients who had further follow-up echocardiographic examinations, 13% developed CTRCD. In the Cox-hazard model, worse Δbasal-LS was significantly associated with CTRCD. By Kaplan-Meier analysis, patients with Δbasal-LS decrease of more than the median value (-9.7%) had significantly worse event-free survival than those with a smaller decrease (p=0.015). Basal-LS significantly decreased prior to development of CTRCD, and worse basal-LS was associated with development of CTRCD in patients receiving anthracycline chemotherapy.


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

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


A case of juvenile fibroadenoma arising from axillary accessory mammary gland

腋窩副乳発生と考えられる若年性線維腺腫の1例

A case is20years old woman. She had previously noticed a mass in the left axilla. The mass grew, so she went to the hospital. Ultrasonography revealed a 71 × 51 mm well-defined tumor in the left axilla. We suspected a benign tumor but could not rule out axillary lymph node metastasis or accessory breast cancer. The findings of fine needle aspiration cytology suggested fibroadenoma or phyllodes tumor. Although we diagnosed fibroadenoma by needle biopsy, a definitive diagnosis was made by tumor resection because it is located in the axilla and large in size, and other diseases such as phyllodes tumors can be distinguished. The histopathological diagnosis of the excised specimen was juvenile fibroadenoma. We report a case of juvenile fibroadenoma arising from the axillary accessory mammary gland.


Phase 1 Dose-Escalation Study of Triweekly Nab-Paclitaxel Combined With S-1 for HER2-Negative Metastatic Breast Cancer

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


Thoracoscopic lobectomy for lung cancer with unilateral absence of pulmonary artery


Tolerability and efficacy of a chemotherapy regimen avoiding Anthracycline for HER2 positive elderly and poor risked breast cancer patients

HER2陽性高齢者乳癌に対するAnthracycline系薬剤回避レジメンの忍容性と有効性についての検討

Tolerability and efficacy of chemotherapy avoiding anthracycline regimen were examined histologically in ER negative and HER2positive elderly and poor risked breast cancer patients because of serious toxicity of Anthracycline regimen. Neo-adjuvant chemotherapy with 4 to 6 courses of Paclitaxel with Trastuzumab was given to 6 patients, Pertuzumab was added in 2 cases to obtain complete response. Adverse events were controllable, the primary treatment was completed without reducing the dose of drugs(RDI was 100%). Clinical CR rate was recognized in all 6 patients and pathological CR was proved in all of the operated5cases.


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


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

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


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

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


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

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


Regional cooperation for cancer patients : A questionnaire clarifying the roles of community doctor

がんの地域連携 かかりつけ医との役割分担に関するアンケート調査

It was suggested long ago that regional cooperation is necessary for cancer patients. Both doctors in base hospitals and community doctors understand the importance of such cooperation. Here we report the results of our widely distributed questionnaire designed to clarify the division of physicians' roles and to strengthen the relationships between base hospital and community doctors. The questionnaire asks whether community doctors can accept cancer patients and what types of medical treatment the doctors can provide for patients with esophageal cancer, lung cancer, breast cancer, and thyroid cancer. The doctors in 289 of 550 (53%) facilities completed and returned the questionnaire. About half of the community doctors responded that they can accept patients with any of the four cancers and can provide most types of the necessary medical examinations and treatments in their daily practices. Most of the community doctors indicated that they could not provide some anti-cancer drugs and supportive drug therapies for breast cancer patients. The development and implementation of a clinical pathway system could enable the participation of more community doctors and base hospital doctors. Although our findings are preliminary, they will contribute to a foundation for building better regional corporative relationships with community doctors who treat cancer patients.


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


Phase II Study of S-1 Combined With Low-Dose Docetaxel as Neoadjuvant Chemotherapy for Operable Breast Cancer Patients (N-1 Study)

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


A case of thoracoscopic medial basal segmentectomy

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

International Journal of Surgery Case Reports


CT lymphography for superficial esophageal cancer. Lymph Node Metastasis in Gastrointestinal Cancer" Part IV. Sentinel node navigation surgery, Chapter 17, Methodology: CT lumphography

Lymph Node Metastasis in Gastrointestinal Cancer. Ed. By Natsugoe S, Springer-Verlag, Tokyo


Case reports : A case of advanced breast cancer with spinal palsy due to cervical bone metastasis who was improved a quality of life by emergent multidisciplinary oncological salvage

乳癌頚椎転移による脊髄麻痺に対して迅速な集学的治療によりQOLの改善が得られた1例

A 60s female complained of right thigh pain caused by bone metastasis from advanced breast cancer. She was introduced to our ward for systemic therapy with palliative radiation to painful osteolytic lesion in the right femur. She suddenly complained of serious pain and motility disturbance in the right upper-extremity two days after her admission. Magnetic resonance imaging(MRI)suggested bone metastasis in the 3rd cervical vertebra which compressed spinal cord. We discussed about an optimal treatment with the orthopedic surgeon and the radiation therapeutic physician, and laminectomy was scheduled promptly. She also had a right femur fracture a day before her planed laminectomy, so she underwent osteosynthesis of the femur together with laminectomy of the cervical vertebra. She also received the irradiation to the 3rd cervical vertebra and the shaft of right femur. She became able to eat with a spoon by herself and her activity of daily living(ADL)have fully recovered by daily rehabilitation. She is receiving chemotherapy in our out-patient clinic now. We recognized that an emergent oncological treatment for the spinal decompression by the bone metastasis could improve the patients' quality of life(QOL)to avoid the permanent paralysis and also their prognoses.


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.


The effects of the herbal medicine Daikenchuto (TJ-100) after esophageal cancer resection, open-label, randomized controlled trial

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


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.


多職種連携による緩和治療が有効であった乳腺悪性葉状腫瘍の1例

多職種連携による緩和治療が有効であった乳腺悪性葉状腫瘍の1例

The case subject was a woman in her50s who consulted her local clinic for the chief complaint of pain extending from the left buttock to the lower leg. A sacral lesion and giant mass in the right breast were observed, and thus on suspicion of breast cancer the subject was referred to our department. The results of needle biopsy led to the definite diagnosis of malignant phyllodes tumor. At the start of treatment the subject presented markedly reduced activities of daily living due to the pain, and upon the introduction of opioids, and performing palliative irradiation for the sacral metastasis, the pain was successfully alleviated relatively quickly. During this period, the primary lesion became ulcerated and progression of anemia was also observed, and therefore upon applying metronidazole ointment and commencing irradiation for the right breast, therapeutic effects such as tumor regression and control of anemia progression were observed. After the initial consultation the subject expressed severe anxiety, and thus intervention was requested from a nurse specialist in cancer care, who sat with the patient when her condition was explained, and listened closely to her anxiety. Thereafter, 2 courses of epirubicin and cyclophosphamide therapy as systemic chemotherapy were administered, however the disease progressed. The subject desired to receive care at a local medical institution, and thus it was decided with the help of a social worker that she be transferred to a hospice in the short-term.


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

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

General Thoracic and Cardiovascular Surgery


Frequent silencing of RASSF1A by DNA methylation in thymic neuroendocrine tumours

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


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

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

The Japanese Journal of Thoracic Surgery


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


Gender differences in clinicopathological features and prognosis of squamous cell carcinoma of the esophagus


肺癌手術における周術期口腔機能管理の術後肺炎予防効果

肺癌手術における周術期口腔機能管理の術後肺炎予防効果

The Journal of the Japanese Association for Chest Surgery


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

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

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

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


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

FDG-PET/CT陽性を示した肺原発良性血管周囲類上皮細胞腫瘍の1例

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

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


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．


A randomized, open label study of the efficacy of prophylactic 24-h low-dose landiolol for atrial fibrillation in transthoracic esophagectomy


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


Thirty percent of ductal carcinoma in situ of the breast in Japan is extremely low-grade ER(+)/HER2(-) type without comedo necrosis

Background Overdiagnosis in mammography (MMG) is a problem. Combination of MMG and ultrasonography for breast cancer screening may increase overdiagnosis. Most cases of overdiagnosis are low-grade ductal carcinoma in situ (LGD), but no reports have focused on them. Materials and methods We immunostained 169 ductal carcinoma in situ (DCIS) cases for ER, PgR, HER2 and Ki67 and classified them into 4 subtypes: ER(+)/HER2(-), ER(+)/HER2(+), ER(-)/HER2(-) and ER(-)/HER2(+). The Ki67 index was used to evaluate the grade of malignancy and examined for correlations with each ER/HER2 subtype and the nuclear grade (NG), with/without comedo necrosis. Results The Ki67 index correlated significantly with NG, both with/without comedo necrosis, and reliably evaluated the grade of malignancy. The index for ER(+)/HER2(-) (n=117, 69.2%) was 7.45±7.10, which was significantly lower than for each of the other types. The index was 5.71±6.94 for ER(+)/HER2(-) without comedo necrosis (n=52, 30.8%), which was significantly lower than with comedo necrosis. This was considered LGD, characterized by absence of microcalcification in MMG and either presence of a solid mass or cystic lesion or absence of hypoechoic areas in ultrasound. Conclusion In Japan, ER(+)/HER2(-) without comedo necrosis accounts for about 30% of DCIS and is LGD. This may be being overdiagnosed. J. Med. Invest. 63: 192-198, August, 2016.


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

The Journal of the Japan Society for Respiratory Endoscopy


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


Assay of serum E2 concentration in postmenopausal breast cancer patients using a high-sensitivity RIA method is generally useful.

Serum E2 levels determined for postmenopausal women by RIA and LC-MS/MS generally correlated well. High-sensitivity RIA is a potentially useful clinical assay, but it overestimated serum E2 in some women. J. Med. Invest. 63: 236-240, August, 2016.


Safe and successful treatment with afatinib in three postoperative non-small cell lung cancer patients with recurrences following gefitinib/erlotinib-induced hepatotoxicity.

Afatinib could be a well-tolerated EGFR-TKI that could be chosen for its relatively low hepatotoxicity, which is attributable to its having a different metabolic mechanism compared to other EGFR-TKIs. J. Med. Invest. 63: 149-151, February, 2016.


XB130 promotes bronchioalveolar stem cell and Club cell proliferation in airway epithelial repair and regeneration

Proliferation of bronchioalveolar stem cells (BASCs) is essential for epithelial repair. XB130 is a novel adaptor protein involved in the regulation of epithelial cell survival, proliferation and migration through the PI3K/Akt pathway. To determine the role of XB130 in airway epithelial injury repair and regeneration, a naphthalene-induced airway epithelial injury model was used with XB130 knockout (KO) mice and their wild type (WT) littermates. In XB130 KO mice, at days 7 and 14, small airway epithelium repair was significantly delayed with fewer number of Club cells (previously called Clara cells). CCSP (Club cell secreted protein) mRNA expression was also significantly lower in KO mice at day 7. At day 5, there were significantly fewer proliferative epithelial cells in the KO group, and the number of BASCs significantly increased in WT mice but not in KO mice. At day 7, phosphorylation of Akt, GSK-3β, and the p85α subunit of PI3K was observed in airway epithelial cells in WT mice, but to a much lesser extent in KO mice. Microarray data also suggest that PI3K/Akt-related signals were regulated differently in KO and WT mice. An inhibitory mechanism for cell proliferation and cell cycle progression was suggested in KO mice. XB130 is involved in bronchioalveolar stem cell and Club cell proliferation, likely through the PI3K/Akt/GSK-3β pathway.


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.


これからの遺伝子診療を考える 遺伝性乳がんについて


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.


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


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.


Monitoring of exhaled carbon monoxide and carbon dioxide during lung cancer operation

Carbon monoxide (CO) is expelled mainly via the lungs, so that exhaled carbon monoxide (Ex-CO) concentration reflects endogenous production. Recent reports have shown that Ex-CO levels are increased in critically ill patients and after anaesthesia and surgery. However, there has been no investigation of the changes in Ex-CO level during a lung operation. We continuously monitored Ex-CO and exhaled carbon dioxide (Ex-CO2) concentrations during surgery for lung cancer. Eighteen lung cancer patients who underwent elective lung cancer lobectomy were enrolled in this study. All patients were endotracheally intubated and ventilated under general anaesthesia. Ex-CO and Ex-CO2 concentrations were separately monitored and recorded continuously using two sets of Carbolyzer® breath analysers (Taiyo Inc., Osaka, Japan). Ex-CO concentration increased rapidly in response to changes in body position from supine to decubitus and was significantly decreased when patients were once again lying back (supine 2). Upon restarting bilateral ventilation, Ex-CO concentration in the operated lung was significantly higher than that in the breathing lung. In the lateral decubitus position, Ex-CO2 concentration showed the same pattern of increase as seen for Ex-CO. In the operated lung, the Ex-CO2 concentrations changed significantly at clamping, declamping and supine 2. In the re-ventilated, operated lung, the Ex-CO2 concentration was significantly lower than in the breathing lung. In the breathing lung, the Ex-CO2 concentration did not exhibit any significant changes over the course of the operation. When breathing was restarted, the Ex-CO level of the target lung was significantly higher than that of the breathing lung. The Ex-CO concentration was also affected by the surgical body position and this change was marked and transient.

European Journal of Cardio-Thoracic Surgery


18F-fluorodeoxyglucose positron emission tomography/computed tomography and the relationship between fluorodeoxyglucose uptake and the expression of hypoxia-inducible factor-1, glucose transporter-1 and vascular endothelial growth factor in thymic epithelial tumours.

OBJECTIVES: The objective of this study was to evaluate the usefulness of (18)F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) and the relationships among the expressions of hypoxia-inducible factor-1 (HIF-1), glucose transporter-1 (Glut-1) and vascular endothelial growth factor (VEGF), histological type, other clinical factors and FDG uptake in thymic epithelial tumours. METHODS: Thirty-three patients who underwent FDG-PET/CT before treatment were reviewed. All types of tumours were reclassified into three subgroups: low-risk thymomas (types A, AB and B1), high-risk thymomas (types B2 and B3) and thymic carcinomas. Tumour contour, pattern of FDG uptake, tumour size and maximum standardized uptake value (SUVmax) were obtained. Expressions of HIF-1, Glut-1 and VEGF were analysed immunohistochemically, and these expressions were evaluated using grading scales. RESULTS: FDG uptake was visually recognized in all (100%) tumours. A homogeneous pattern of FDG uptake was increasingly observed in the order of low-risk thymomas to high-risk thymomas to thymic carcinomas (P = 0.016). SUVmax for thymic carcinomas was significantly higher than that for thymomas (P = 0.008). With the optimal cut-off value of SUVmax of 5.6, the sensitivity, specificity and accuracy for diagnosing thymic carcinoma were 0.75, 0.80 and 0.79, respectively. Regarding the mean scoring of HIF-1, Glut-1 and VEGF, increasing trends were observed in the order of low-risk thymomas to high-risk thymomas to thymic carcinomas. Tumour size revealed a significant correlation with SUVmax (r = 0.60, P < 0.001), and the expression of HIF-1 showed a moderate association, but the expression of Glut-1 showed no correlation with SUVmax. Regarding correlations between the expression of the three markers, there were moderate associations between HIF-1 and Glut-1, and HIF-1 and VEGF, and a significant correlation between Glut-1 and VEGF (r = 0.60, P < 0.001). In type B1 thymoma, HIF-1 and Glut-1 were partly expressed in non-neoplastic immature lymphocytes. CONCLUSIONS: FDG-PET/CT should be performed in patients with tumours in the anterior mediastinum because the pattern of FDG uptake and SUVmax are useful in the differential diagnosis of thymic epithelial tumours. Furthermore, the expressions of HIF-1, Glut-1 and VEGF might be associated with malignancy of thymic epithelial tumours. In contrast, FDG uptake might be dependent on tumour size rather than Glut-1 overexpression.