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

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


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

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

The Journal of Medical Investigation : JMI


Therapeutic Strategy for Chylothorax After Esophagectomy: Lymphangiography with an Inguinal Intranodal Approach


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.


Identification of fibrocyte cluster in tumors reveals the role in antitumor immunity by PD-L1 blockade.

fibrocytes do not. Tumor-infiltrating fibrocytes acquire myofibroblast-like phenotypes through transforming growth factor β (TGF-β)/small mothers against decapentaplegic (SMAD) signaling. Thus, TGF-βR/SMAD inhibitor enhances the antitumor effects of dual VEGF and PD-L1 blockade by regulating fibrocyte differentiation. Fibrocytes are highlighted as regulators of the response to programmed death 1 (PD-1)/PD-L1 blockade.

fibrocytes is enhanced by anti-PD-L1 antibody. Peritumoral implantation of fibrocytes enhances the antitumor effect of PD-L1 blockade in vivo; CD86


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.


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

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


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.


Analysis of the chemotactic factors for tumor-infiltrating fibrocytes and their prognostic significances in lung cancer.

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


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.


ypN0 in Patients with Definitive cN-positive Status After Preoperative Treatment Is a Prognostic Factor in Esophageal Cancer

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


Spontaneous esophageal perforation within a hiatal hernia: A case report

International Journal of Surgery Case Reports


Drug-induced interstitial pneumonia during perioperative chemotherapy for breast cancer

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

The Journal of Medical Investigation : JMI


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


A Case of Radiation-associated Angiosarcoma Presenting as Massive Pleural Effusion.

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


Intrathymic Plasmablasts Are Affected in Patients With Myasthenia Gravis With Active Disease.

Our findings confirmed a correlation between increased frequency of intrathymic plasmablasts and disease activity before thymectomy. We postulate that activated intrathymic plasmablasts endow pathogenic capacity in MG.

Neurology® Neuroimmunology & Neuroinflammation


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.


The role of virtual-assisted lung mapping 2.0 combining microcoils and dye marks in deep lung resection

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

Journal of Thoracic and Cardiovascular Surgery


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.


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

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


食道癌手術における高度胸膜癒着症例への対処

食道癌手術における高度胸膜癒着症例への対処


Preoperative computer tomography-guided indocyanine green injection is associated with successful localization of small pulmonary nodules

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


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

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


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

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


気管支鏡の破損を分析する

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

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

The Journal of the Japan Society for Respiratory Endoscopy


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

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


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

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

General Thoracic and Cardiovascular Surgery


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

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


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

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


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

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


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


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．


A CASE OF VAGUS NERVE SCHWANNOMA DIFFICULT TO DISTINGUISH FROM LYMPH NODAL METASTASIS OF ESOPHAGEAL CANCER.

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

The Journal of Medical Investigation : JMI


Japanese Journal of Cancer and 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.


The sterno-tracheal distance is an important factor of anastomotic leakage of retrosternal gastric tube reconstruction after esophagectomy

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


A case of long-term unchanged calcifying fibrous tumor

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

General Thoracic and Cardiovascular Surgery


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


Effects of excitation light intensity on parathyroid autofluorescence with a novel near-infrared fluorescence imaging system : two surgical case reports


Safe central venous catheters for esophageal cancer treatment

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


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


内視鏡手術の教育システム

内視鏡手術の教育システム

Official Journal of the Japan Association of Endocrine Surgeons and the Japanese Society of Thyroid Surgery

日本内分泌・甲状腺外科学会雑誌


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

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


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

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


Prognostic significance of GAD1 overexpression in patients with resected lung adenocarcinoma

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


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

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


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


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


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

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


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


「がんゲノム医療」によせて

「がんゲノム医療」によせて


Acase of advanced colon cancer arising from a colonic graft foran esophago-bronchial fistula : A case report.

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


Surgical training in video-assisted neck surgery-based thyroidectomy using fresh frozen human cadavers.

Endoscopic surgery has been introduced in various surgical fields. Endoscopic surgery requires different skills from open surgery due to the restricted surgical field and difficulty in identifying anatomical structures from certain viewpoints. Therefore, surgeons need to undergo sufficient surgical training before performing such surgery in the clinical setting. We examined the utility of fresh frozen human cadavers for surgical training aimed at introducing video-assisted neck surgery (VANS) at our department. First, we performed surgical training using fresh human cadavers four times. Next, we performed hemi-thyroidectomy with VANS in 5 clinical patients. After the cadaver training and the actual surgery, the surgeons evaluated each step of the surgical procedure using a 3-point scale. In the cadaver training, the scores for steps : creation of a subcutaneous tunnel and lifting up the skin flap and pre-thyroid muscles were higher than other steps. And a tracheal injury occurred as a complication. However, we were able to recognize anatomical structures under the endoscopic view. And it was also useful for confirming the role of surgical staff and simulating the placement of surgical equipment. Surgical training using fresh frozen human cadavers was effective at introducing a new surgical method. J. Med. Invest. 66 : 293-296, August, 2019.


Mediastinal Parathyroidectomy Using a Cervical Approach Under a Pneumomediastinum

Video-assisted thoracoscopic surgery (VATS) and robotic surgery are minimally invasive surgeries for mediastinal parathyroid adenomas. However, a transthoracic approach is often difficult in the cervicothoracic transition area because of the limited visual field. We report a novel minimally invasive surgery for an ectopic parathyroid adenoma in the middle mediastinum using a cervical approach under a pneumomediastinum.

Seminars in Thoracic and Cardiovascular Surgery


Mediastinal Parathyroidectomy Using a Cervical Approach Under a Pneumomediastinum.


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.

The Journal of Medical Investigation : JMI


A case of painful Hashimoto s thyroiditis with difficulty of different from subacute thyroiditis

亜急性甲状腺炎との鑑別が困難であった橋本病急性増悪の1例

橋本病急性増悪は，橋本病に急性炎症症状を伴う稀な疾患である．今回，亜急性甲状腺炎と鑑別が困難であった橋本病急性増悪の1例を経験したので報告する．症例は14歳，女性．2年前に学校検診で橋本病と診断された．1年10カ月前に甲状腺腫大増悪，頸部右側の圧痛を認めた．血液検査所見では，甲状腺機能正常であり，抗Tg抗体277IU/mL，抗TPO抗体246IU/mLと高値であった．白血球，CRPは正常値であり，赤沈の軽度亢進を認めた．亜急性甲状腺炎もしくは橋本病急性増悪が疑われ，NSAIDsが投与された．しかし，頸部疼痛が改善せずprednisolone(PSL)投与が開始された．治療中，疼痛部位は移動した．また，血液検査所見で自己抗体値が低下したため，亜急性甲状腺炎の可能性も否定できなかった．PSL投与後，症状は軽減したが，PSL漸減で疼痛が再燃し，PSL中止が困難であった．再燃を繰り返すことから橋本病急性増悪と診断した．PSLの離脱困難なため手術の方針となり，甲状腺全摘を行った．

Official Journal of the Japan Association of Endocrine Surgeons and the Japanese Society of Thyroid Surgery

日本内分泌・甲状腺外科学会雑誌


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

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


Surgical treatment of locally advanced papillary thyroid carcinoma after response to lenvatinib

Differentiated thyroid carcinomas (DTC) have good prognoses after complete resection. Nevertheless, when DTC is associated with an aerodigestive invasion, curative surgery is difficult to perform. However, there is no established neoadjuvant therapy for advanced DTC. A 73-year-old man with thyroid papillary carcinoma was referred to our hospital. A computed tomography examination revealed a tumor in the upper right lobe of the thyroid, and multiple bilateral enlarged lymph nodes in the neck, involving the surrounding structures. The enlarged lymph node at the right upper neck was suspected to have invaded the right internal jugular vein, and the left paratracheal lymph node was suspected to have invaded the cervical esophagus and trachea. The tumor was considered resectable; however, surgery would have been highly invasive. Therefore, we initiated neoadjuvant therapy with lenvatinib. After administration of lenvatinib, the tumor decreased in size by 84.3% and the cervical lymph nodes by 56.0%. The patient underwent a total thyroidectomy, modified neck dissection, a resection of the muscular layer of the esophagus, and a tracheal sleeve resection and reconstruction. The SELECT trial demonstrated that lenvatinib had high response rate with short response time, in patients with radioiodine-refractory DTC. The results suggested that lenvatinib could be effective as neoadjuvant therapy. For an advanced DTC that requires removal through invasive surgery, preoperative lenvatinib treatment might be one of the options for a less invasive surgery.

International Journal of Surgery Case Reports


A case of metastatic follicular thyroid carcinoma complicated with Graves' disease after total thyroidectomy

Thyroid cancer and Graves' disease may present simultaneously in one patient. The incidence of the development of hyperthyroidism from metastatic differentiated thyroid carcinoma is rare. We herein report a case of metastatic follicular carcinoma complicated with Graves' disease after total thyroidectomy. A 57-year-old woman underwent right hemithyroidectomy for follicular carcinoma. Metastatic lesions appeared in the lungs and skull two years after the first surgery, and remnant thyroidectomy was performed for radioactive iodine-131 (RAI) therapy, during which the TSH receptor antibody (TRAb) was found to be negative. The patient was treated with RAI therapy four times for four years and was receiving levothyroxine suppressive therapy. Although radioiodine uptake was observed in the lesions after the fourth course of RAI therapy, metastatic lesions had progressed. Four years after the second surgery, she had heart palpitations and tremors. Laboratory data revealed hyperthyroidism and positive TRAb. She was diagnosed with Graves' disease and received a fifth course of RAI therapy. 131I scintigraphy after RAI therapy showed strong radioiodine uptake in the metastatic lesions. As a result, the sizes and numbers of metastatic lesions decreased, and thyroid function improved. Metastatic lesions produced thyroid hormone and caused hyperthyroidism. RAI therapy was effective for Graves' disease and thyroid carcinoma.


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


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

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


Pentraxin 3 deficiency enhances features of chronic rejection in a mouse orthotopic lung transplantation model

Chronic lung allograft dysfunction (CLAD) is a serious complication after lung transplantation and thought to represent chronic rejection. Increased expression of Pentraxin 3 (PTX3), an acute phase protein, was associated with worse outcome in lung transplant patients. To determine the role of recipient PTX3 in development of chronic rejection, we used a minor alloantigen-mismatched murine orthotopic single lung transplant model. Male C57BL/10 mice were used as donors. Male PTX3 knockout (KO) mice and their wild type (WT) littermates on 129/SvEv/C57BL6/J background were used as recipients. In KO recipients, 7/13 grafted lungs were consolidated without volume recovery on CT scan, while only 2/9 WT mice showed similar graft consolidation. For grafts where lung volume could be reliably analyzed by CT scan, the lung volume recovery was significantly reduced in KO mice compared to WT. Interstitial inflammation, parenchymal fibrosis and bronchiolitis obliterans scores were significantly higher in KO mice. Presence of myofibroblasts and lymphoid aggregation was significantly enhanced in the grafts of PTX3 KO recipients. Recipient PTX3 deficiency enhanced chronic rejection-like lesions by promoting a fibrotic process in the airways and lung parenchyma. The underlying mechanisms and potential protective role of exogenous PTX3 as a therapy should be further explored.


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


外科診療におけるチーム医療の現況と展望 4．周術期の口腔ケア-食道癌，肺癌手術における周術期口腔機能管理-