Publications by authors named "Takuro Miyazaki"

126 Publications

Certified thoracic surgeons in Japan: a national database survey on risk-adjusted mortality associated with lung resection.

Surg Today 2021 Jan 30. Epub 2021 Jan 30.

Department of Surgical Oncology, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan.

Purpose: We investigated the association between the number of certified general thoracic surgeons (GTSs) and the mortality after lung cancer surgery, based on the data from the National Clinical Database (NCD).

Methods: We analyzed the characteristics and operative and postoperative data of 120,946 patients who underwent lung cancer surgery in one of the 905 hospitals in Japan. The number of GTSs in each hospital was categorized as 0, 1-2, or 3 or more. Multivariable analysis was applied to adjust the patients' preoperative risk factors, as identified in a previous study. We calculated 95% confidence intervals (CI) for the mortality rate based on the odds ratios (ORs).

Results: The patients' characteristics were distributed almost uniformly regardless of the number of GTSs. Crude mortality according to the number of GTSs of 0, 1-2, or 3 or more was 0.9%, 0.8%, and 0.7%, respectively (p = 0.03). However, after adjustment, the ORs for 1-2 and 3 or more GTSs (reference: 0) were 0.86 (p = 0.23, 95% CI: 0.67-1.10) and 0.84 (p = 0.18, 95% CI: 0.64-1.09), respectively. The number of GTSs did not have a significant association with mortality. Similar results were observed for patients in the lobectomy cohort.

Conclusion: Low surgical mortality was consistent, regardless of the number of GTSs in each hospital.
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http://dx.doi.org/10.1007/s00595-021-02227-3DOI Listing
January 2021

Hybrid video-assisted thoracoscopic surgery sleeve lobectomy for non-small cell lung cancer: a case report.

J Thorac Dis 2020 Nov;12(11):6836-6846

Department of Thoracic Surgery, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute, Shenyang, China.

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http://dx.doi.org/10.21037/jtd-20-2679DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7711411PMC
November 2020

Hic-5 is required for activation of pancreatic stellate cells and development of pancreatic fibrosis in chronic pancreatitis.

Sci Rep 2020 11 5;10(1):19105. Epub 2020 Nov 5.

Department of Biochemistry, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo, 142-8555, Japan.

Accumulated evidence suggests that activated pancreatic stellate cells (PSCs) serve as the main source of the extracellular matrix proteins accumulated under the pathological conditions leading to pancreatic fibrosis in chronic pancreatitis (CP). However, little is known about the mechanisms of PSC activation. PSCs have morphologic and functional similarities to hepatic stellate cells, which are activated by hydrogen peroxide-inducible clone-5 (Hic-5), a TGF-β1-induced protein. In this study, we investigated whether Hic-5 activates PSCs, which promote pancreatic fibrosis development in CP. Hic-5-knockout and wild type mice were subjected to caerulein injection to induce CP. Hic-5 expression was strongly upregulated in activated PSCs from human CP tissue and from mouse pancreatic fibrosis in caerulein-induced CP. Hic-5 deficiency significantly attenuated mouse pancreatic fibrosis and PSC activation in the experimental murine CP model. Mechanistically, Hic-5 knock down significantly inhibited the TGF-β/Smad2 signaling pathway, resulting in reduced collagen production and α-smooth muscle actin expression in the activated PSCs. Taken together, we propose Hic-5 as a potential marker of activated PSCs and a novel therapeutic target in CP treatment.
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http://dx.doi.org/10.1038/s41598-020-76095-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7645689PMC
November 2020

Preoperative tracheal resection and reconstruction simulations with patient-specific three-dimensional models.

Gen Thorac Cardiovasc Surg 2021 Mar 29;69(3):593-596. Epub 2020 Oct 29.

Department of Surgical Oncology, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan.

Three-dimensional (3D) printers are increasingly being used for a variety of applications. In the surgical field, patient-specific organ models are increasingly being used as preoperative simulators for complicated surgeries. In this study, we describe the use of patient-specific 3D models for tracheal resection. We performed preoperative simulations for two patients diagnosed with tracheal ganglioneuroma and adenoid cystic carcinoma; the mimic operations suggested the necessity of a short cuff intubation tube across the surgical field, indicating the recommended amount of dissection around the trachea and bilateral hilum prior to tracheal reconstruction. The postoperative courses were free from any anastomotic or pulmonary complications. We described the availability of preoperative simulations for complicated tracheal resection and reconstruction using patient-specific 3D printed models. Mimic operations using the 3D printed models allowed accurate preparation and confidence in selection of the optimal surgical strategy.
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http://dx.doi.org/10.1007/s11748-020-01531-yDOI Listing
March 2021

Short-Physical Performance Battery (SPPB) score is associated with postoperative pulmonary complications in elderly patients undergoing lung resection surgery: A prospective multicenter cohort study.

Chron Respir Dis 2020 Jan-Dec;17:1479973120961846

Department of Rehabilitation Medicine, 88380Nagasaki University Hospital, Nagasaki, Japan.

Elderly patients awaiting lung resection surgery often have poor physical function, which puts them at a high risk of postoperative pulmonary complications. The aim of this study was to investigate the impact of preoperative physical performance on postoperative pulmonary complications in patients awaiting lung resection surgery. In this prospective multicenter cohort study, the characteristics of patients and postoperative pulmonary complications were compared between subjects with low (<10) and high (≥10) Short Physical Performance Battery (SPPB) scores. Postoperative pulmonary complications were defined as over grade II in Clavien-Dindo classification system. We estimated the effects of physical performance on postoperative pulmonary complications using multivariable hierarchical logistic regression. The postoperative pulmonary complications were compared between 331 patients in the high and 33 patients in the low SPPB group. Patients in the low SPPB score group had a significantly higher rate of postoperative pulmonary complications (p < 0.001). Low SPPB score was associated with a higher risk of postoperative pulmonary complications (odds ratio, 8.80; p < 0.001). The SPPB is a clinically useful evaluation tool to assess surgical patients' physical performance. The low physical performance indicated by the SPPB may be predictive of postoperative pulmonary complications after lung resection surgery. Clinical Trials. University hospital Medical Information Network Center (UMIN-CTR) UMIN000021875.
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http://dx.doi.org/10.1177/1479973120961846DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7545757PMC
September 2020

Presence of heat shock protein 47-positive fibroblasts in cancer stroma is associated with increased risk of postoperative recurrence in patients with lung cancer.

Respir Res 2020 Sep 14;21(1):234. Epub 2020 Sep 14.

Department of Respiratory Medicine, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan.

Background: Heat shock protein 47 (HSP47), a collagen-binding protein, has a specific role in the intracellular processing of procollagen production. HSP47 expression is associated with cancer growth and metastasis in several types of cancers. However, none of the studies have assessed whether HSP47 expression is associated with the risk of postoperative recurrence of lung cancer until now. Therefore, we aimed to assess this association.

Methods: The study population consisted of a cohort of consecutive patients who underwent surgery for lung cancer at Nagasaki University Hospital, Nagasaki, Japan, from January 2009 to December 2010. Patient characteristics, survival and disease-free survival (DFS), and laboratory findings were compared between patients who tested positive and negative for HSP47 expression in lung cancer cells and between those who showed high and low numbers of HSP47-positive fibroblasts in cancer stroma.

Results: A total of 133 patients underwent surgery for lung cancer. Sixty-seven patients (50.4%) had HSP47-positive cancer cells, and 91 patients (68.4%) had a higher number of HSP47-positive fibroblasts. The patients with a high number of HSP47-positive fibroblasts had a shorter DFS than those with a low number of HSP47-positive fibroblasts. Multivariate analysis identified only the presence of a high number of HSP47-positive fibroblasts as an independent risk factor for recurrence of lung cancer after surgery (odds ratio, 4.371; 95% confidence interval, 1.054-29.83; P = 0.042).

Conclusion: The present study demonstrated that the presence of a high number of HSP47-positive fibroblasts in the cancer stroma was a risk factor for recurrence of lung cancer after surgery.
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http://dx.doi.org/10.1186/s12931-020-01490-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7488681PMC
September 2020

How to reduce bleeding complications during thoracoscopic anatomic pulmonary resection.

J Thorac Dis 2020 May;12(5):1758-1761

Department of Surgical Oncology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.

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http://dx.doi.org/10.21037/jtd-20-1624DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7330412PMC
May 2020

Enhanced airway stenting using a preoperative, three-dimensionally printed airway model simulation.

Gen Thorac Cardiovasc Surg 2020 Dec 11;68(12):1591-1593. Epub 2020 Jun 11.

Department of Surgical Oncology, Nagasaki University Graduate School of Biomedical Science, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan.

Three-dimensionally printed organ models that facilitate preoperative simulations have the potential to improve outcomes of surgical procedures. Here, we report a case involving a 54-year-old man diagnosed with lung cancer of the right upper bronchus that was invading the right main bronchus. A right upper lobectomy with carinoplasty was performed. Although complete excision of the tumor was achieved, exertional dyspnea redeveloped 4 months post-surgery. Chest computed tomography revealed that airway stenosis caused by granulation had deformed the airway. Ablation of the granulation and airway stenting was required to improve the patient's symptoms. Prior to performing airway stenting, a three-dimensionally printed airway model was constructed, and the Y-shaped silicone stent used was modified in accordance with the model. After stenting, both the right and left bronchi were preserved, and the patient's symptoms improved. The three-dimensional printed airway model enhanced the accuracy and safety of the airway stenting procedure performed.
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http://dx.doi.org/10.1007/s11748-020-01404-4DOI Listing
December 2020

Factors Influencing Functional Exercise Capacity After Lung Resection for Non-Small Cell Lung Cancer.

Integr Cancer Ther 2020 Jan-Dec;19:1534735420923389

Department of Cardiopulmonary Rehabilitation Science, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.

We investigated, in patients who underwent lung resection for non-small cell lung cancer (NSCLC), the magnitude of early limitation in functional exercise capacity and the associations with pre- and postoperative factors. Consecutive patients with preoperative clinical stage I to IIIA NSCLC who underwent lung resection were prospectively enrolled. We measured functional exercise capacity (6-minute walk distance [6MWD]) and skeletal muscle strength (handgrip [HF] and quadriceps force [QF]) within 2 days prior to surgery and on day 7 postoperatively. Two hundred eighteen participants were recruited (median age 69 years) of whom 49 developed postoperative complications (POCs). 6MWD was markedly decreased (514 m vs 469 m, < .001); HF and QF were slightly decreased following surgery. Multiple linear regression showed that preoperative vital capacity ( < .01), QF ( < .05), the duration of chest tube drainage ( < .001), and presence of POCs ( < .05) were significant predictors. However, intraoperative factors were not significantly associated with the decline in 6MWD. These results suggest that patients with preoperative impairments in pulmonary function and muscle strength, and those who require prolonged chest tube drainage or develop POCs are likely to have impaired exercise capacity. Therefore, individual assessment and follow-up of patients with such factors is indicated.
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http://dx.doi.org/10.1177/1534735420923389DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7273541PMC
June 2020

Surgery or stereotactic body radiotherapy for metachronous primary lung cancer? A propensity score matching analysis.

Gen Thorac Cardiovasc Surg 2020 Nov 23;68(11):1305-1311. Epub 2020 May 23.

Department of Surgical Oncology, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan.

Objective: We compared outcomes after surgery or stereotactic body radiotherapy (SBRT) among patients with metachronous primary lung cancer (MPLC).

Methods: Patients with MPLC were treated with either surgery (2008-2018) or SBRT (2010-2018). We used propensity score matching (PSM) to reduce bias from various clinicopathological factors. MPLC was defined by the Martini and Melamed criteria.

Results: Of 77 patients, 51 underwent surgery and 26 received SBRT. Most median clinicopathological characteristics did not significantly differ between the surgery and SBRT groups (male sex: 67% vs 65%; age: 73 vs 77 years; time after first surgery: 6.2 vs 4.7 years; lobectomy as first procedure: 82% vs 85%; second tumor size: 11 vs 12 mm; clinical stage I: 96% vs 100%; CEA: 2.9 vs 3.0 ng/ml). However, the surgery group had significantly more ipsilateral second tumors (n = 71, 58%, P = 0.003), better performance status (P = 0.03), and preserved lung function (P = 0.02). Surgery, thus, tended to be selected for patients with good physical function and for the MPLC in the contralateral side. Five-year overall survival did not significantly differ between the surgery and SBRT groups, either before PSM (86.5% vs 65.8%, P = 0.24, log-rank) or after PSM (100% vs 84.4%, P = 0.73).

Conclusions: Surgery and SBRT for MPLC patients are safe and feasible treatments with similar outcomes. However, this finding should be verified by a random controlled trial with a larger study cohort.
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http://dx.doi.org/10.1007/s11748-020-01394-3DOI Listing
November 2020

Calpain proteolytic systems counteract endothelial cell adaptation to inflammatory environments.

Inflamm Regen 2020 2;40. Epub 2020 Apr 2.

Department of Biochemistry, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo, 142-8555 Japan.

Vascular endothelial cells (ECs) make up the innermost surface of arteries, veins, and capillaries, separating the remaining layers of the vessel wall from circulating blood. Under non-inflammatory conditions, ECs are quiescent and form a robust barrier structure; however, exposure to inflammatory stimuli induces changes in the expression of EC proteins that control transcellular permeability and facilitate angiogenic tube formation. Increasing evidence suggests that dysfunction in intracellular proteolytic systems disturbs EC adaptation to the inflammatory environment, leading to vascular disorders such as atherosclerosis and pathological angiogenesis. Recent work has highlighted the contribution of the calpain-calpastatin stress-responsive intracellular proteolytic system to adaptation failure in ECs. In this review, we summarize our current knowledge of calpain-calpastatin-mediated physiologic and pathogenic regulation in ECs and discuss the molecular basis by which disruption of this system perturbs EC adaptation to the inflammatory environment.
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http://dx.doi.org/10.1186/s41232-020-00114-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7114782PMC
April 2020

Effects of lipid metabolism on mouse incisor dentinogenesis.

Sci Rep 2020 03 20;10(1):5102. Epub 2020 Mar 20.

Department of Pharmacology, School of Dentistry, Showa University, 1-5-8 Hatanodai, Shinagawa, Tokyo, 142-8555, Japan.

Tooth formation can be affected by various factors, such as oral disease, drug administration, and systemic illness, as well as internal conditions including dentin formation. Dyslipidemia is an important lifestyle disease, though the relationship of aberrant lipid metabolism with tooth formation has not been clarified. This study was performed to examine the effects of dyslipidemia on tooth formation and tooth development. Dyslipidemia was induced in mice by giving a high-fat diet (HFD) for 12 weeks. Additionally, LDL receptor-deficient (Ldlr) strain mice were used to analyze the effects of dyslipidemia and lipid metabolism in greater detail. In the HFD-fed mice, incisor elongation was decreased and pulp was significantly narrowed, while histological findings revealed disappearance of predentin. In Ldlr mice fed regular chow, incisor elongation showed a decreasing trend and pulp a narrowing trend, while predentin changes were unclear. Serum lipid levels were increased in the HFD-fed wild-type (WT) mice, while Ldlr mice given the HFD showed the greatest increase. These results show important effects of lipid metabolism, especially via the LDL receptor, on tooth homeostasis maintenance. In addition, they suggest a different mechanism for WT and Ldlr mice, though the LDL receptor pathway may not be the only factor involved.
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http://dx.doi.org/10.1038/s41598-020-61978-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7083963PMC
March 2020

International expert consensus on the management of bleeding during VATS lung surgery.

Ann Transl Med 2019 Dec;7(23):712

Division of Thoracic Surgery, Sun Yat-Sen Cancer Center, Taipei, Taiwan, China.

Intraoperative bleeding is the most crucial safety concern of video-assisted thoracic surgery (VATS) for a major pulmonary resection. Despite the advances in surgical techniques and devices, intraoperative bleeding is still not rare and remains the most common and potentially fatal cause of conversion from VATS to open thoracotomy. Therefore, to guide the clinical practice of VATS lung surgery, we proposed the International Interest Group on Bleeding during VATS Lung Surgery with 65 experts from 10 countries in the field to develop this consensus document. The consensus was developed based on the literature reports and expert experience from different countries. The causes and incidence of intraoperative bleeding were summarised first. Seven situations of intraoperative bleeding were collected based on clinical practice, including the bleeding from massive vessel injuries, bronchial arteries, vessel stumps, and bronchial stumps, lung parenchyma, lymph nodes, incisions, and the chest wall. The technical consensus for the management of intraoperative bleeding was achieved on these seven surgical situations by six rounds of repeated revision. Following expert consensus statements were achieved: (I) Bleeding from major vascular injuries: direct compression with suction, retracted lung, or rolled gauze is useful for bleeding control. The size and location of the vascular laceration are evaluated to decide whether the bleeding can be stopped by direct compression or by ligation. If suturing is needed, the suction-compressing angiorrhaphy technique (SCAT) is recommended. Timely conversion to thoracotomy with direct compression is required if the operator lacks experience in thoracoscopic angiorrhaphy. (II) Bronchial artery bleeding: pre-emptive clipping of bronchial artery before bronchial dissection or lymph node dissection can reduce the incidence of bleeding. Bronchial artery bleeding can be stopped by compression with the suction tip, followed by the handling of the vascular stump with energy devices or clips. (III) Bleeding from large vessel stumps and bronchial stumps: bronchial stump bleeding mostly comes from accompanying bronchial artery, which can be clipped for hemostasis. Compression for hemostasis is usually effective for bleeding at the vascular stump. Otherwise, additional use of hemostatic materials, re-staple or a suture may be necessary. (IV) Bleeding from the lung parenchyma: coagulation hemostasis is the first choice. For wounds with visible air leakage or an insufficient hemostatic effect of coagulation, suturing may be necessary. (V) Bleeding during lymph node dissection: non-grasping en-bloc lymph node dissection is recommended for the nourishing vessels of the lymph node are addressed first with this technique. If bleeding occurs at the site of lymph node dissection, energy devices can be used for hemostasis, sometimes in combination with hemostatic materials. (VI) Bleeding from chest wall incisions: the chest wall incision(s) should always be made along the upper edge of the rib(s), with good hemostasis layer by layer. Recheck the incision for hemostasis before closing the chest is recommended. (VII) Internal chest wall bleeding: it can usually be managed with electrocoagulation. For diffuse capillary bleeding with the undefined bleeding site, compression of the wound with gauze may be helpful.
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http://dx.doi.org/10.21037/atm.2019.11.142DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6989967PMC
December 2019

Alleviation of murine osteoarthritis by deletion of the focal adhesion mechanosensitive adapter, Hic-5.

Sci Rep 2019 10 31;9(1):15770. Epub 2019 Oct 31.

Department of Biochemistry, Showa University School of Medicine, Tokyo, Japan.

Excessive mechanical stress is a major cause of knee osteoarthritis. However, the mechanism by which the mechanical stress begets osteoarthritis development remains elusive. Hydrogen peroxide-inducible clone-5 (Hic-5; TGFβ1i1), a TGF-β inducible focal adhesion adaptor, has previously been reported as a mediator of mechanotransduction. In this study, we analyzed the in vivo function of Hic-5 in development of osteoarthritis, and found that mice lacking Hic-5 showed a significant reduction in development of osteoarthritis in the knee. Furthermore, we found reduced expression of catabolic genes, such as metalloproteinase-13 and a disintegrin and metalloproteinase with thrombospondin type 1 motif 5 in osteoarthritic lesions in mice lacking Hic-5. During osteoarthritis development, Hic-5 is detected in chondrocytes of articular cartilage. To investigate the role of Hic-5 in chondrocytes, we isolated chondrocytes from articular cartilage of wild type and Hic-5-deficient mice. In these primary cultured chondrocytes, Hic-5 deficiency resulted in suppression of catabolic gene expression induced by osteoarthritis-related cytokines such as tumor necrosis factor α and interleukin 1β. Furthermore, Hic-5 deficiency in chondrocytes suppressed catabolic gene expression induced by mechanical stress. Revealing the regulation of chondrocyte catabolism by Hic-5 contributes to understanding the pathophysiology of osteoarthritis induced by mechanical stress.
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http://dx.doi.org/10.1038/s41598-019-52301-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6823501PMC
October 2019

A case of emergent operation for a life-threatening infectious mediastinal cyst.

Int J Surg Case Rep 2019 18;64:150-153. Epub 2019 Oct 18.

Department of Surgical Oncology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan; Medical-Engineering Hybrid Professional Development Program, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.

Purpose: Congenital mediastinal cysts are an uncommon but important diagnostic group. Most of these cysts are benign and asymptomatic in adults. However, some of them are clinically problematic due to the compression of neighboring organs, infection, or perforation.

Case Presentation: A 20-year-old man presented with severe dyspnea. Imaging revealed a mediastinal cyst in the subcarinal space compressing his right pulmonary artery and airway, which was later diagnosed as a bronchogenic cyst. Due to quick symptom exacerbation, emergent cyst wall fenestration was performed through video-assisted thoracic surgery with "stand-by" extracorporeal membrane oxygenation. Complete cyst resection was difficult owing to adhesion of the cyst to the surrounding organs. The symptoms immediately resolved after surgery and the postoperative course was uneventful.

Conclusion: Mediastinal bronchogenic cysts with life-threatening complications are rarely reported in adults. However, this case was life-threatening due to airway and vascular compression; emergent surgical care should be considered in such cases.
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http://dx.doi.org/10.1016/j.ijscr.2019.10.022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6831818PMC
October 2019

No drain policy for "ultimate" enhanced recovery after surgery.

J Thorac Dis 2019 Sep;11(Suppl 15):S1900-S1902

Department of Surgical Oncology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.

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http://dx.doi.org/10.21037/jtd.2019.08.46DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6783769PMC
September 2019

Light-at-night exposure affects brain development through pineal allopregnanolone-dependent mechanisms.

Elife 2019 09 30;8. Epub 2019 Sep 30.

Laboratory of Integrative Brain Sciences, Department of Biology, Waseda University, Tokyo, Japan.

The molecular mechanisms by which environmental light conditions affect cerebellar development are incompletely understood. We showed that circadian disruption by light-at-night induced Purkinje cell death through pineal allopregnanolone (ALLO) activity during early life in chicks. Light-at-night caused the loss of diurnal variation of pineal ALLO synthesis during early life and led to cerebellar Purkinje cell death, which was suppressed by a daily injection of ALLO. The loss of diurnal variation of pineal ALLO synthesis induced not only reduction in pituitary adenylate cyclase-activating polypeptide (PACAP), a neuroprotective hormone, but also transcriptional repression of the cerebellar gene that produces PACAP, with subsequent Purkinje cell death. Taken together, pineal ALLO mediated the effect of light on early cerebellar development in chicks.
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http://dx.doi.org/10.7554/eLife.45306DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6850767PMC
September 2019

Evaluation of Protein-Protein Interactions using an On-Membrane Digestion Technique.

J Vis Exp 2019 07 19(149). Epub 2019 Jul 19.

Division of Biological Chemistry, Department of Molecular Biology, Showa University School of Pharmacy;

Numerous intracellular proteins physically interact in accordance with their intracellular and extracellular circumstances. Indeed, cellular functions largely depend on intracellular protein-protein interactions. Therefore, research regarding these interactions is indispensable to facilitating the understanding of physiologic processes. Co-precipitation of associated proteins, followed by mass spectrometry (MS) analysis, enables the identification of novel protein interactions. In this study, we have provided details of the novel technique of immunoprecipitation-liquid chromatography (LC)-MS/MS analysis combined with on-membrane digestion for the analysis of protein-protein interactions. This technique is suitable for crude immunoprecipitants and can improve the throughput of proteomic analyses. Tagged recombinant proteins were precipitated using specific antibodies; next, immunoprecipitants blotted onto polyvinylidene difluoride membrane pieces were subjected to reductive alkylation. Following trypsinization, the digested protein residues were analyzed using LC-MS/MS. Using this technique, we were able to identify several candidate associated proteins. Thus, this method is convenient and useful for the characterization of novel protein-protein interactions.
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http://dx.doi.org/10.3791/59733DOI Listing
July 2019

Successful treatment based on molecular biological assessment of invasive anaplastic lymphoma kinase-positive inflammatory myofibroblastic tumor of the lung.

Surg Case Rep 2019 Jul 24;5(1):118. Epub 2019 Jul 24.

Division of Surgical Oncology, Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan.

Background: Inflammatory myofibroblastic tumor (IMT) of the lung is rare. This disease often shows neoplastic features with anaplastic lymphoma kinase positiveness as well as inflammatory features, such as steroid-responsive immunoglobulin G4 (IgG4)-related sclerosing disease. Since many cases have been reported as advanced, various treatment strategies should be considered based on clinical and biological features of each case.

Case Presentation: We report a 49-year-old male with IMT, which seemed invading the left atrium from preoperative imaging modalities. Serological and pathological examinations from the biopsy specimen revealed high expression of anaplastic lymphoma kinase expression in the tumor. On the other hand, IgG4/IgG ration in the tumor was small, where a therapeutic effect of steroid was not expected, leading to surgical treatment rather than a steroid administration. The tumor was completely resected en bloc with the right lower lobe of the lung and a part of the left atrium. The postoperative course of the patient was uneventful. The patient has remained recurrence free over 5 years from the surgery.

Conclusion: In this case, preoperative biological assessment prior to the treatment led to a good clinical course. We believe that molecular biological examination is important in the determination of treatment strategy for this rare disease as well as imaging modalities.
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http://dx.doi.org/10.1186/s40792-019-0674-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6656828PMC
July 2019

Utilization of Natural Detergent Potassium Laurate for Decellularization in Lung Bioengineering.

Tissue Eng Part C Methods 2019 08;25(8):459-471

1Department of Surgical Oncology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.

Impact Statement: Recent advances in tissue engineering using decellularized organ scaffolds have expanded the possibilities for organ replacement therapy. However, detergent-based decellularization itself damages the extracellular matrix (ECM), which results in failure associated with the transplanted bioengineered organ. This study determined that potassium laurate (PL), a natural detergent, significantly reduces lung ECM damage during the decellularization process compared with protocols using sodium dodecyl sulfate. PL-decellularized lungs showed better microarchitecture preservation and low biological reactions after subcutaneous implantation. PL-decellularized scaffolds supported rat lung endothelial cell attachment/proliferation and the bioengineered lungs significantly reduced lung congestion after transplantation.
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http://dx.doi.org/10.1089/ten.TEC.2019.0016DOI Listing
August 2019

Postoperative acute exacerbation of interstitial pneumonia in pulmonary and non-pulmonary surgery: a retrospective study.

Respir Res 2019 Jul 15;20(1):154. Epub 2019 Jul 15.

Department of Respiratory Medicine, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan.

Background: Acute exacerbation of interstitial pneumonia (AE-IP) is a serious complication of pulmonary surgery in patients with IP. However, little is known about AE-IP after non-pulmonary surgery. The aim of this study was to determine the frequency of AE-IP after non-pulmonary surgery and identify its risk factors.

Methods: One hundred and fifty-one patients with IP who underwent pulmonary surgery and 291 who underwent non-pulmonary surgery were retrospectively investigated.

Results: AE-IP developed in 5 (3.3%) of the 151 patients in the pulmonary surgery group and 4 (1.4%) of the 291 in the non-pulmonary surgery group; the difference was not statistically significant. A logistic regression model showed that serum C-reactive protein (CRP) was a predictor of AE-IP in the non-pulmonary surgery group (odds ratio 1.187, 95% confidence interval 1.073-1.344, P = 0.002).

Conclusions: This is the first study to compare the frequency of AE-IP after pulmonary surgery with that after non-pulmonary surgery performed under the same conditions. The results suggest that the frequency of AE-IP after non-pulmonary surgery is similar to that after pulmonary surgery. A high preoperative C-reactive protein level is a potential risk factor for AE-IP after non-pulmonary surgery.
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http://dx.doi.org/10.1186/s12931-019-1128-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6631983PMC
July 2019

Editorial on "Albumin-to-fibrinogen ratio as a prognostic biomarker to predict clinical outcome of non-small cell lung cancer individuals".

J Thorac Dis 2019 May;11(Suppl 9):S1241-S1244

Department of Surgical Oncology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.

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http://dx.doi.org/10.21037/jtd.2019.03.02DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6560581PMC
May 2019

Thrombolytic Therapy for Acute Ischemic Stroke: Past and Future.

Curr Pharm Des 2019 ;25(3):242-250

Division of Pharmacology, Department of Pharmacology, Toxicology and Therapeutics, Showa University School of Pharmacy, Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan.

Background: Thromboembolic ischemic stroke, which is mainly caused by hypertension, as well as plasma dyslipidemia, arterial fibrillation and diabetes, is a leading cause of death in the US and other countries. Numerous clinical trials for thrombolytic drugs, which aimed to pharmacologically dissolve thrombi, were conducted in the 1950s, when the first thrombolytic therapy was performed.

Methods: In this study, we summarize the pathophysiologic features of ischemic stroke, and the history of thrombolytic therapy, and discuss the recent progress that has been made in the ongoing development of thrombolytic drugs.

Conclusion: Thrombolytic therapy is sometimes accompanied by harmful hemorrhagic insults; accordingly, a window of time wherein therapy can safely be performed has been established for this approach. Several basic and clinical studies are ongoing to develop next-generation thrombolytic drugs to expand the time window.
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http://dx.doi.org/10.2174/1381612825666190319115018DOI Listing
February 2020

Concurrent chemoradiotherapy using cisplatin and S-1, followed by surgery for stage II/IIIA non-small cell lung cancer.

Gen Thorac Cardiovasc Surg 2019 Jun 23;67(6):537-543. Epub 2019 Jan 23.

Department of Surgical Oncology, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan.

Objectives: Because chemoradiotherapy using cisplatin and S-1, an oral fluoropyrimidine, is effective for unresectable non-small cell lung cancer (NSCLC), an induction setting was used in a multicenter phase II study (Clinical trial number: UMIN000008205). The correlations of relapse and clinicopathological factors were analyzed.

Methods: We defined locally advanced NSCLC as pathologically proven chest wall invasion or hilar and/or mediastinal lymph node metastases by endobronchial ultrasound-guided transbronchial needle aspiration. The patients received two courses of S-1 administration for 14 days and intravenous cisplatin injection on day 8. A total dose of 40 Gy radiotherapy was concurrently received. Surgical resection was performed after completion of the treatment.

Results: Of the 23 eligible patients, 18 had stage IIIA and 5 had stage IIB NSCLC. Twenty of the eligible patients (87.0%) completed the regimen. Six (26.1%) complete responses were identified and 12 cases (52.2%) were histopathologically downstaged by induction chemoradiotherapy (ICRT). The 3-year overall survival rate was 58.1% and relapse-free survival (RFS) rate was 52.0%, respectively. Among several clinicopathological parameters, univariate RFS analysis identified that only downstaging was significantly associated with longer RFS times (p = 0.003). The radiological response did not reflect pathological response. When the variables of preoperative pathologically proven N2 metastasis, pathological ICRT effectiveness, and downstaging were included in the Cox proportional hazard modes, only the parameter of downstaging displayed significant hazard ratio (hazard ratio 0.13, p = 0.010).

Conclusion: This protocol is considered an option among preoperative therapies and has obvious benefits for pathologically downstaged cases.

Clinical Trial Number: UMIN000008205.

Trial Registration Date: June 19, 2012.
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http://dx.doi.org/10.1007/s11748-018-01058-3DOI Listing
June 2019

Replacement of Rat Tracheas by Layered, Trachea-Like, Scaffold-Free Structures of Human Cells Using a Bio-3D Printing System.

Adv Healthc Mater 2019 04 11;8(7):e1800983. Epub 2019 Jan 11.

Department of Surgical Oncology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, 852-8501, Japan.

Current scaffold-based tissue engineering approaches are subject to several limitations, such as design inflexibility, poor cytocompatibility, toxicity, and post-transplant degradation. Thus, scaffold-free tissue-engineered structures can be a promising solution to overcome the issues associated with classical scaffold-based materials in clinical transplantation. The present study seeks to optimize the culture conditions and cell combinations used to generate scaffold-free structures using a Bio-3D printing system. Human cartilage cells, human fibroblasts, human umbilical vein endothelial cells, and human mesenchymal stem cells from bone marrow are aggregated into spheroids and placed into a Bio-3D printing system with dedicated needles positioned according to 3D configuration data, to develop scaffold-free trachea-like tubes. Culturing the Bio-3D-printed structures with proper flow of specific medium in a bioreactor facilitates the rearrangement and self-organization of cells, improving physical strength and tissue function. The Bio-3D-printed tissue forms small-diameter trachea-like tubes that are implanted into rats with the support of catheters. It is confirmed that the tubes are viable in vivo and that the tracheal epithelium and capillaries proliferate. This tissue-engineered, scaffold-free, tubular structure can represent a significant step toward clinical application of bioengineered organs.
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http://dx.doi.org/10.1002/adhm.201800983DOI Listing
April 2019

An aggregate score to stratify the technical complexity of video-assisted thoracoscopic lobectomy.

Interact Cardiovasc Thorac Surg 2019 05;28(5):728-734

Department of Thoracic Surgery, The Leeds Teaching Hospitals NHS Trust, Leeds, UK.

Objectives: The purpose of this study was to develop a score to predict the complexity of video-assisted thoracoscopic surgery (VATS) lobectomies preoperatively.

Methods: One hundred and thirty-nine consecutive patients undergoing VATS lobectomy operated on by a single surgeon as the first operator were included. Complex operations were defined as: operation time >180 min (corresponding to the 75th percentile) or a conversion to thoracotomy. Several patient-related baseline and radiological variables were tested for a possible association with surgical complexity by logistic regression analysis. An aggregate score was created by weighing the regression estimates of the significant predictors. Patients were then grouped in classes of risk according to their scores. Finally, the score was validated in an external population of 154 VATS lobectomy patients.

Results: Twenty-nine VATS lobectomies (21%) were classified as complex. The following variables were found to be significantly associated with a complex operation and were used to calculate the risk score in each patient (1 point each): male (P = 0.006), presence of thick pleura (P = 0.003), presence of emphysema (P = 0.001), enlarged hilar nodes (P = 0.003). Patients were grouped in 4 classes showing an incremental incidence of complex operations (P < 0.0001): score 0, 7.4%; score 1, 18%; score 2, 27%; score >2, 67%. In the external validation set, the score confirmed its association with the incidence of complex operations (P < 0.001): score 0, 7.3%; score 1, 10%; score 2, 16%; score >2 50%.

Conclusions: The complexity score appeared to be reproducible in an external setting and can be used to preoperatively identify appropriate candidates for VATS lobectomies to improve the efficiency and safety of the training phase.
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http://dx.doi.org/10.1093/icvts/ivy319DOI Listing
May 2019

Minute ventilation-to-carbon dioxide slope is associated with postoperative survival after anatomical lung resection.

Lung Cancer 2018 11 4;125:218-222. Epub 2018 Oct 4.

Department of Thoracic Surgery, St. James's University Hospital, Leeds, UK.

Objectives: The aim of the study was to identify whether ventilation-to-carbon dioxide output (V/V ) slope obtained from cardiopulmonary exercise test (CPET) as part of the preoperative functional workup was an independent prognostic factor for short and long-term survival after major lung resection.

Patients And Methods: 974 consecutive patients undergoing lobectomy (n = 887) or segmentectomy (n = 87) between April 2014 to March 2018 were included. 209 (22%) underwent CPET, and pulmonary function tests and several clinical factors including age, sex, performance status and comorbidities were retrospectively investigated to identify the prognostic factors with a multivariable Cox regression analysis.

Results: Among the patients with measured V/V , the incidence of cardiopulmonary complications in patients with high V/V slope (>40) was 37% (19 of 51) vs. 27% (33 of 121) in those with lower slope values (p = 0.19). The 90-day mortality in patients with high V/V slope (n = 8) was 16% vs. 5% (n = 6) in those with lower slope values (p = 0.03). No overall difference in 2-year mortality was identified between the two groups (VE/VCO2 > 40: 70% (54-80) vs. VE/VCO2 ≤ 40: 72% (63-80), log-rank test, p = 0.39). In a Cox regression analysis V/V values were associated with poorer 2-year survival (HR 1.05, 95% CI 1.01-1.10, p = 0.030).

Conclusions: We found that V/V slope was an independent prognostic factor for the 90-day mortality and 2-year survival after anatomic pulmonary resection. This finding may assist during the multidisciplinary treatment decision-making process in high-risk patients with lung cancer.
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http://dx.doi.org/10.1016/j.lungcan.2018.10.003DOI Listing
November 2018

L-Leucine increases the daily body temperature and affords thermotolerance in broiler chicks.

Asian-Australas J Anim Sci 2019 Jun 29;32(6):842-848. Epub 2018 Oct 29.

Graduate School of Bioresource and Bioenvironmental Sciences, Kyushu University, Fukuoka 819-0395, Japan.

Objective: Heat stress poses an increasing threat for poultry production. Some amino acids have been found to play critical roles in affording thermotolerance. Recently, it was found that in ovo administration of L-leucine (L-Leu) altered amino acid metabolism and afforded thermotolerance in heat-exposed broiler chicks.

Methods: In this study, two doses (35 and 70 μmol/egg) of L-Leu were administered in ovo on embryonic day 7 to determine their effect on rectal temperature (RT), body weight (BW) and thyroid hormones at hatching. Changes in RT, BW, and thermotolerance in post-hatched chicks were also analyzed.

Results: It was found that in ovo administration of L-Leu dose-dependently reduced RT and plasma thyroxine (T4) level just after hatching. In post-hatched neonatal broiler chicks, however, the higher dose of L-Leu administered in ovo significantly increased RT without affecting BW gain. In chicks that had been exposed to heat stress, the RT was significantly lowered by in ovo administration of L-Leu (high dose) in comparison with the control chicks under the same high ambient temperature (HT: 35°C±1°C, 120 min).

Conclusion: In ovo administration of L-Leu in a high dose contributed to an increased daily body temperature and afforded thermotolerance under HT in neonatal broiler chicks.
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http://dx.doi.org/10.5713/ajas.18.0677DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6498076PMC
June 2019

Endothelial calpain systems orchestrate myofibroblast differentiation during wound healing.

FASEB J 2019 02 10;33(2):2037-2046. Epub 2018 Sep 10.

Department of Biochemistry, Showa University School of Medicine, Shinagawa-ku, Tokyo, Japan.

The transformation of fibroblasts to myofibroblasts plays a major role in fibrogenic responses during dermal wound healing. We show a contribution of calpain systems (intracellular regulatory protease systems) in vascular endothelial cells (ECs) to myofibroblast differentiation in wound sites. Dermal wound healing experiments in mice found that calpastatin (an endogenous inhibitor of calpains) is enriched in preexisting vessels but not in newly formed capillaries. Transgenic overexpression of calpastatin in ECs delayed wound healing in mice as well as reducing the keratinocyte layer, extracellular matrix deposition, and myofibroblast accumulation in wound sites. EC and leukocyte markers, however, remain unchanged. Calpastatin overexpression reduced the expression of genes encoding platelet-derived growth factor-B and PDGF receptor-β (PDGFR-β). Topical application of platelet-derived growth factor-BB-containing ointment to wounds accelerated healing in control mice, but calpastatin overexpression prevented this acceleration. In cultured human dermal fibroblasts, α-smooth muscle actin and PDGFR-β were up-regulated by coculturing with ECs, but this action was inhibited by suppression of EC calpain activity. EC-driven transformation of mouse dermal fibroblasts was also suppressed by calpastatin overexpression in ECs. These results suggest that endothelial calpain systems influence PDGFR-β signaling in fibroblasts, EC-driven myofibroblast differentiation, and subsequent fibrogenic responses in wounds.-Miyazaki, T., Haraguchi, S., Kim-Kaneyama, J.-R., Miyazaki, A. Endothelial calpain systems orchestrate myofibroblast differentiation during wound healing.
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http://dx.doi.org/10.1096/fj.201800588RRDOI Listing
February 2019

Balloon-Based Organ Retractor With Increased Safety and Reduced Invasiveness During Video-Assisted Thoracoscopic Surgery.

Surg Innov 2018 Oct 2;25(5):435-443. Epub 2018 Jul 2.

1 Department of Surgical Oncology, Nagasaki University Graduate School of Biomedical Sciences, Japan.

Objectives: In recent years, video-assisted thoracoscopic surgery (VATS) has increasingly become the preferred technique for thoracic surgery. However, the inherent characteristics of the lungs as large, soft, slippery, and delicate creates difficulties for pulmonary surgery. In this article, we outline the development and assessment of a balloon-based organ retractor for VATS via collaboration between medical and engineering personnel.

Methods: A dry lab trial and accompanying questionnaire assessment were performed by a group of thoracic surgeons. Objective pressure measurements were obtained, and animal experiment on pigs was performed.

Results: In the dry lab trial, use of the developed organ retractor required significantly less time and resulted in fewer difficulties than using a Cherry Dissector. The measured pressure per mm of the developed retractor was clearly lower than that for the Cherry Dissector. The questionnaire completed by the surgeons following the dry lab and animal experiments showed that most of the surgeons (7 surgeons out of 9) were satisfied with the quality of the balloon-based retractor based on a score of 3.13 ± 0.28 (mean ± standard deviation) out of 4.0. During the animal experiment, the balloon-based retractor provided stable and clear viewing with minimal need for adjustment.

Conclusion: This balloon-based retractor could contribute to increased safety and less-invasive VATS.
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http://dx.doi.org/10.1177/1553350618784473DOI Listing
October 2018