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Third Lecture of Internal Medicine

Research room overview

The Third Lecture of Internal Medicine started in 1971 and has engaged in the treatment and research in respiratory tract, liver, kidneys, and lipids. However, due to the recent high demand for specialty, we now specialize in respiratory tract and contribute to medical education and research as the main therapeutic center in Wakayama prefecture.

In this lecture, we have supervisory physicians and specialists from the Respiratory Society, Society for Respiratory Endoscopy, and Society of Allergology. Not only do we provide the latest diagnoses or treatment of overall respiratory diseases including bronchial asthma, chronic obstructive lung disease (COPD), and lung cancer, but we also devote ourselves to the education and training of respiratory specialists and research. We actively engage in diagnoses and treatment of COPD and bronchial asthma, which have higher prevalence rates than other respiratory diseases. In our outpatient clinic, we have devices to measure airway hypersensitivity and fine respiratory function and a spirogram. We have staff on site ready to assess respiratory function. In addition, we apply a device to measure exhaled nitric oxide in clinical practice to reduce the burden on patients with airway inflammation, a major symptom of bronchial asthma. 　Furthermore, we provide COPD patients with not only drug therapies but also exercise tolerance assessment as well as pulmonary rehabilitation in an aggressive way to improve their activity of daily living (ADL). Regarding lung cancer, we hold conferences with Department of Thoracic Surgery and Department of Radiology on a regular basis to provide combined modality diagnoses and therapies. For patients with advanced cancer, we provide palliative treatment for various symptoms, such as pain and respiratory destress, in cooperation with the Palliative Care Unit. The total number of new patients with respiratory diseases has exceeded 6000, including 1000 cases of bronchial asthma, 700 cases of COPD, 300 cases of interstitial pneumonia, and 600 cases of lung cancer. We perform over 200 bronchoscopies each year. We also conduct epidemiological research on respiratory diseases and offer awareness programs to people and healthcare professionals in Wakayama prefecture by holding seminars and lectures.

Education overview (Junior resident training, Senior resident training, Graduate school, etc.)

For junior residents (1 to 2 years post-gradation), we provide training rotations in departments where experience is considered necessary in becoming a certified internist. 　Residents aiming to become specialists in respiratory medicine may consult us on training schedule in related departments. The major purpose of the training is to learn basic clinical techniques as attending physicians of hospitalized patients under supervisory physicians. However, upon request, residents can start training in test and treatment techniques specific to respiratory diseases, such as respiratory function test, airway hypersensitivity test, and bronchoscopy. Senior residents (3 to 4 years post-graduation) start training to become specialists in each field. As a general rule, residents receive clinical training in our department during the third year and in our department or affiliated hospitals during the fourth year. Senior residents aim not only to become certified internists but also to be certified as supervisory physicians by the Respiratory Society, Society of Allergology, and Society for Respiratory Endoscopy. Senior residents start training in treatment as attending physicians of hospitalized patients; however, our department provides treatment as a team so that residents can have extended experiences in various diseases and clinical practice. Additionally, senior residents learn the techniques for tests, including respiratory function test, bronchoscopy, airway hypersensitivity test, and all-night polysomnography, as well as image diagnosis techniques for CT and X-ray. They also aim to acquire proficiency in diagnosis and treatment of respiratory diseases, such as bronchial asthma, COPD, lung cancer, respiratory infections, and interstitial pneumonia; and to put them into practice.

The graduate school students can achieve the degree within 4 years of enrollment. During the first year, students choose a research field and initiate research while receiving clinical training in hospital wards. During the second through fourth years, students focus on the basics and clinical research to complete the degree, and each of them prepares his/her doctoral thesis. In general, the graduate school is a four-year program; however, students with an excellent research achievement may graduate in 3 years.

Research overview and achievements

We focus on COPD and bronchial asthma in clinical research. COPD was recognized as a disease with poor therapeutic outcomes; however, it is now considered to be a disease “that can be prevented and can be treated.” As for COPD, we evaluate efficacies of aggressive treatment with drug therapy in combination with pulmonary rehabilitation. We also conduct research to reveal the pathology of patients whose respiratory function is compromised in a short period of time and to develop a biomarker reflecting the airway inflammation and its pathology (such as analysis of liquid on airway surface). The major symptoms of bronchial asthma that should be treated are airway hypersensitivity and airway inflammation. However, it was difficult to assess the condition repeatedly in a noninvasive way. As for bronchial asthma, we search for a physiological marker of hypersensitivity that can replace the airway hypersensitivity test, and assess airway inflammation using noninvasive methods, such as exhaled breath condensate (exhaled air during resting ventilation that is cold condensed and collected) and exhaled nitric oxide measurement. We are the pioneer in Japan in applying our research to clinical practice.

As basic research, we measure substances related to inflammation to reveal the pathologies of COPD and asthma using various clinical samples, such as induced sputum, exhaled breath condensate, liquid on airway surface, and serum marker; assess the quantities of oxidative and nitrogen stress; and examine the intracellular signaling mechanism associated with expanded or advanced inflammations. Especially in the pathophysiology of COPD and asthma, an aggravation mechanism resulting in death or hospitalization and airway remodeling mechanism leading to refractory conditions remain to be elucidated. Accordingly, clarification of these issues are required. In our department, we conduct basic assessments using cultured cells, such as airway epithelial cell and fibroblasts, in combination with stimuli of viral infection and oxidative and nitrogen stress to examine such issues in the future.

Latest original article

  1. Tanaka A, Akamatsu H, Kawabata H, Ariyasu H, Nakamura Y, Yamamoto N: Peripheral pulmonary carcinoid tumor diagnosed by endobronchial ultrasound guided bronchoscopy. Respirol Case Rep 4(1): 10-12, 2016
  2. Imai H, Mori K, Wakuda K, Ono A, Akamatsu H, Shukuya T, Taira T, Kenmotsu H, Naito T, Kaira K, Murakami H, Endo M, Nakajima T, Yamamoto N, Takahashi T: Progression- free survival, post-progression survival, and tumor response as surrogate markers for overall survival in patients with extensive small cell lung cancer. Ann Thorac Med 10(1): 61-66, 2015
  3. Wakuda K, Kenmotsu H, Naito T, Akamatsu H, Ono A, Shukuya T, Nakamura Y, Tsuya A, Murakami H, Takahashi T, Endo M, Nakajima T, Yamamoto N: Efficacy of rechallenge chemotherapy in patients with sensitive relapsed small cell lung cancer. Am J Clin Oncol 38(1): 28-32, 2015
  4. Ko R, Kenmotsu H, Hisamatsu Y, Akamatsu H, Omori S, Nakashima K, Oyakawa T, Wakuda K, Shukuya T, Ono A, Imai H, Taira T, Naito T, Murakami H, Mori K, Endo M, Ohde Y, Takahashi K, Takahashi T: The effect of gefitinib in patients with postoperative recurrent non-small cell lung cancer harboring mutations of the epidermal growth factor receptor. Int J Clin Oncol 20(4): 668-673, 2015
  5. Kimura M, Naito T, Kenmotsu H, Taira T, Wakuda K, Oyakawa T, Hisamatsu Y, Tokito T, Imai H, Akamatsu H, Ono A, Kaira K, Murakami H, Endo M, Mori K, Takahashi T, Yamamoto N: Prognostic impact of cancer cachexia in patients with advanced non-small cell lung cancer. Support Care Cancer 23(6): 1699-1708, 2015
  6. Akamatsu H, Ono A, Shukuya T, Tsuya A, Nakamura Y, Kenmotsu H, Naito T, Murakami H, Endo M, Nakajima T, Yamamoto N, Takahashi T: Disease flare after gefitinib discontinuation. Respir Investig 53(2): 68-72, 2015
  7. Matsunaga K, Hayata A, Akamatsu K, Hirano T, Tamada T, Kamei T, Tsuda T, Nakamura H, Takahashi T, Hozawa S, Mori Y, Sakamoto Y, Kimura K, Katsumata U, Miura M, Ichinose M: Stratifying the risk of COPD exacerbation using the modified Medical Research Council scale: A multicenter cross-sectional CAP study. Respir Investig 53(2): 82-85, 2015
  8. Li YJ, Kanaji N, Wang XQ, Sato T, Nakanishi M, Kim M, Michalski J, Nelson AJ, Farid M, Basma H, Patil A, Toews ML, Liu X, Rennard SI:  Prostaglandin E2 switches from a stimulator to an inhibitor of cell migration after epithelial-to-mesenchymal transition. Prostaglandins Other Lipid Mediat 116-117: 1-9, 2015
  9. Imai H, Kaira K, Mori K, Ono A, Akamatsu H, Taira T, Yoshino R, Kenmotsu H, Saitoh J, Harada H, Naito T, Murakami H, Tomizawa Y, Matsuura M, Saito R, Nakajima T, Yamada M, Takahashi T: Comparison of platinum combination re-challenge therapy and docetaxel monotherapy in non-small cell lung cancer patients previously treated with platinum-based chemoradiotherapy. SpringerPlus 4: 152, 2015
  10. Watanabe M, Kawaguchi T, Isa S, Ando M, Tamiya A, Kubo A, Saka H, Takeo S, Adachi H, Tagawa T, Kakegawa S, Yamashita M, Kataoka K, Ichinose Y, Takeuchi Y, Sakamoto K, Matsumura A, Koh Y: Ultra-sensitive detection of the pretreatment EGFR T790M mutation in non-small-cell lung cancer patients with an EGFR-activating mutation using droplet digital PCR. Clin Cancer Res 21(15): 3552-3560, 2015
  11. Miura S, Kaira K, Kaira R, Akamatsu H, Ono A, Shukuya T, Tsuya A, Nakamura Y, Kenmotsu H, Naito T, Murakami H, Takahashi T, Endo M, Yamamoto N: The efficacy of amrubicin on central nervous system  metastases originating from small-cell lung cancer: a case series of eight patients. Invest New Drugs 33(3): 755-760, 2015
  12. Matsunaga K, Hirano T, Oka A, Tanaka A, Kanai K, Kikuchi T, Hayata A, Akamatsu H, Akamatsu K, Koh Y, Nakanishi M, Minakata Y, Yamamoto N: Progression of Irreversible Airflow Limitation in Asthma: Correlation with Severe Exacerbations. J Allergy Clin Immunol Pract 3(5): 759-764, 2015
  13. Nishio M, Horiike A, Murakami H, Yamamoto N, Kaneda H, Nakagawa K, Horinouchi H, Nagashima M, Sekiguchi M, Tamura T: Phase Ⅰ study of the HER3-targeted antibody patritumab (U3-1287) combined with erlotinib in Japanese patients with non-small cell lung cancer. Lung Cancer 88: 275-281, 2015
  14. Morimoto A, Mogami T, Watanabe M, Iijima K, Akiyama Y, Katayama K, Futami T, Yamamoto N, Sawada T, Koizumi F, Koh Y: High-Density Dielectrophoretic Microwell Array for Detection, Capture, and Single-Cell Analysis of Rare Tumor Cells in Peripheral Blood. PLoS One 10(6): e0130418, 2015
  15. Serizawa M, Yokota T, Hosokawa A, Kusafuka K, Sugiyama T, Tsubosa Y, Yasui H, Nakajima T, Koh Y: The efficacy of uracil DNA glycosylase pretreatment in amplicon-based massively parallel sequencing with DNA extracted from archived formalin-fixed paraffin-embedded esophageal cancer tissues. Cancer Genet 208(9):415-27, 2015
  16. Paoletti C, Muñiz MC, Thomas DG, Griffith KA, Kidwell KM, Tokudome N, Brown ME, Aung K, Miller MC, Blossom DL, Schott AF, Henry NL, Ras JM, Connelly MC, Chianese DA, Hayes DF: Development of circulating tumor cell-endocrine therapy index in patients with hormone receptor-positive breast cancer. Clin Cancer Res 21(11):2487-2498, 2015
  17. Abe T, Takeda K, Ohe Y, Kudoh S, Ichinose Y, Okamoto H, Yamamoto N, Yoshioka H, Minato K, Sawa T, Iwamoto Y, Saka H, Mizusawa J, Shibata T, Nakamura S, Ando M, Yokoyama A, Nakagawa K, Saijo N, Tamura T: Randomized phase III Trial Comparing Weekly Docetaxel Plus Cisplatin Versus Docetaxel Monotherapy Every 3 Weeks in Elderly Patients With Advanced Non-Small-Cell Lung Cancer: The Intergroup Trial JCOG0803/WJOG4307L. J Clin Oncol 33(6): 575-581, 2015
  18. Yang JC, Wu YL, Schuler M, Sebastian M, Popat S, Yamamoto N, Zhou C, Hu CP, O'Byrne K, Feng J, Lu S, Huang Y, Geater SL, Lee KY, Tsai CM, Gorbunova V, Hirsh V, Bennouna J, Orlov S, Mok T: Afatinib versus cisplatin-based chemotherapy for EGFR mutation-positive lung adenocarcinoma (LUX-Lung 3 and LUX-Lung 6): analysis of overall survival data from two randomised, phase 3 trials. Lancet Oncol 16(2): 141-151, 2015
  19. Tamura K, Aiba K, Saeki T, Nakanishi Y, Kamura T, Baba H, Yoshida K, Yamamoto N, Kitagawa Y, Maehara Y, Shimokawa M, Hirata K, Kitajima M, CINV Study Group of Japan: Testing the effectiveness of antiemetic guidelines: results of a prospective registry by the CINV Study Group of Japan. Int J Oncol 20(5): 855-865, 2015
  20. Shukuya T, Yamanaka T, Seto T, Daga H, Goto K, Saka H, Sugawara S, Takahashi T, Yokota S, Kaneda H, Kawaguchi T, Nagase S, Oguri T, Iwamoto Y, Nishimura T, Hattori Y, Nakagawa K, Nakanishi Y, Yamamoto N: West Japan Oncology Group: Nedaplatin plus docetaxel versus cisplatin plus docetaxel for advanced or relapsed squamous cell carcinoma of the lung (WJOG5208L): a randomised, open-label, phase 3 trial. Lancet Oncol 16(16): 1630-1638, 2015
  21. Murakami H, Ikeda M, Okusaka T, Inaba T, Iguchi H, Yagawa K, Yamamoto N: A phase I study of MEDI-575, a PDGFRα monoclonal antibody, in Japanese patients with advanced solid tumors. Cancer Chemother Pharmacol 76(3): 631-639, 2015
  22. Kato T, Yoshioka H, Okamoto I, Yokoyama A, Hida T, Seto T, Kiura K, Massey D, Seki Y, Yamamoto N: Afatinib versus cisplatin plus pemetrexed in Japanese patients with advanced non-small cell lung cancer harboring activating EGFR mutations: Subgroup analysis of LUX-Lung 3. Cancer Sci 106(9): 1202-1211, 2015
  23. Yang JC, Sequist LV, Geater SL, Tsai CM, Mok TS, Schuler M, Yamamoto N, Yu CJ, Ou SH, Zhou C, Massey D, Zazulina V, Wu YL: Clinical activity of afatinib in patients with advanced non-small-cell lung cancer harbouring uncommon EGFR mutations: a combined post-hoc analysis of LUX-Lung 2, LUX-Lung 3, and LUX-Lung 6. Lancet Oncol 16(7): 830-838, 2015
  24. Kanai K, Koarai A, Shishikura Y, Sugiura H, Ichikawa T, Kikuchi T, Akamatsu K, Hirano T, Nakanishi M, Matsunaga K, Minakata Y, Ichinose M: Cigarette smoke augments MUC5AC production via the TLR3-EGFR pathway in airway epithelial cells. Respir Investig 53(4): 137-148, 2015