Journal of Nippon Medical School
Online ISSN : 1347-3409
Print ISSN : 1345-4676
ISSN-L : 1345-4676
Volume 86 , Issue 1
Showing 1-11 articles out of 11 articles from the selected issue
Review
  • Go Kanzaki, Yusuke Okabayashi, Kiyotaka Nagahama, Ryuji Ohashi, Nobuo ...
    2019 Volume 86 Issue 1 Pages 2-9
    Published: January 15, 2019
    Released: March 26, 2019
    JOURNALS FREE ACCESS

    Abnormal proliferation of plasma cells and some monoclonal B cells frequently cause the secretion of monoclonal immunoglobulins or immunoglobulin fragments into the serum, causing monoclonal gammopathy, which leads to various diseases including renal diseases. Therefore, monoclonal gammopathy is frequently associated with kidney diseases, including glomerular and tubulointerstitial diseases. Glomerular disease, with the deposition of monoclonal immunoglobulins or their components, includes monoclonal immunoglobulin deposition disease (MIDD), AL or AH amyloidosis, type I cryoglobulinemia, proliferative glomerulonephritis with monoclonal IgG deposits (PGNMID), immunotactoid glomerulopathy, and fibrillary glomerulonephritis. In addition, tubulointerstitial diseases with the deposition of monoclonal immunoglobulins or their components are constituted by light chain (myeloma) cast nephropathy, light chain associated Fanconi's syndrome (light chain proximal [crystal] tubulopathy), and crystal-storing histiocytosis. In the present review article, we demonstrate the clinicopathological characteristics of MIDD, which is one of the representative diseases of plasma cell dyscrasias, and discuss various renal diseases with the deposition of monoclonal immunoglobulins or their components in glomeruli and the tubulointerstitium. We recommend that these renal diseases are arranged as one disease category, "renal diseases with deposition of monoclonal immunoglobulins or their components", in order to simplify the understanding of complicated diseases in plasma cell dysplasia.

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  • Naomi Kamimura, Alexander M. Wolf, Yoshiko Iwai
    2019 Volume 86 Issue 1 Pages 10-14
    Published: January 15, 2019
    Released: March 26, 2019
    JOURNALS FREE ACCESS

    Immune checkpoint inhibitors are causing a paradigm shift in cancer treatment. Immune checkpoint molecules such as programmed cell death protein 1 (PD-1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) dampen T cell activation to avoid autoimmunity and the destructive effects of an excessive inflammatory response. Immune checkpoint signaling can be exploited by tumors to escape host immune surveillance, and immune checkpoint inhibitors enhance antitumor immunity by releasing the brakes on the immune system. PD-1 was identified in 1992 by Honjo and colleagues at Kyoto University. Studies in animal models revealed that PD-1 blockade can inhibit tumorigenesis and tumor metastasis. In addition, PD-1 blockade showed fewer adverse effects than CTLA-4 blockade. Based on these findings, a humanized monoclonal antibody against human PD-1 called nivolumab was developed. Since PD-1 blockade targets lymphocytes rather than tumor cells, the therapeutic effects last longer, even if mutations occur during tumorigenesis. Furthermore, because it does not depend on specific tumor antigens, PD-1 blockade can be applied to various kinds of tumors.

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Originals
  • Keigo Ito, Shin-ichi Ansai, Hidehisa Saeki
    2019 Volume 86 Issue 1 Pages 15-21
    Published: January 15, 2019
    Released: March 26, 2019
    JOURNALS FREE ACCESS

    Background: Intratumoral lymphocytes are a defining feature of spiradenoma; however, there have only been a few reports on the phenotypic features of non-epithelial cells. Spiradenomas also contain numerous cells positive for S-100 protein and the nature of these cells is still controversial. Methods: We performed a clinicopathological and immunohistochemical study of ten cases of spiradenoma. Results: The study included seven men and three women. On histopathological examination, spiradenoma could be divided into two types: the vascular proliferating (VP) type (five cases) that featured granulation tissue with edema, vascular proliferation, and inflammatory cell infiltration into the stroma, and the common type (five cases), which did not include any of the aforementioned features. Immunohistochemical staining demonstrated a large number of cells positive for S-100 protein. These included cells with large pale nuclei, dendritic cells, and a few cells with small dark nuclei that were also positive for α-smooth muscle actin. Most of the cells infiltrating the parenchymata of these lesions were CD3-positive. The proportions of CD4-positive and CD8-positive cells were almost equal or CD8-positive cells were predominant. CD20+ cells were observed in five spiradenomas. In painful lesions, there were numerous nerve fibers near the tumor. Conclusions: In spiradenoma, CD3+ T cells were mainly seen in the parenchyma and CD8+ cells were predominant over CD4+ cells in most cases. CD20+ cells showed focal infiltration of the parenchyma and stroma, especially in VP-type lesions. S-100 protein-positive cells in spiradenoma contained not only Langerhans cells, but also cells with myoepithelial differentiation.

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  • Yasuyuki Kitagawa, Toshihiko Ito, Yoshihiro Mizuno, Yoshihiro Sudo, Yo ...
    2019 Volume 86 Issue 1 Pages 22-26
    Published: January 15, 2019
    Released: March 26, 2019
    JOURNALS FREE ACCESS

    Background: Diagnosing bone metastasis in patients without a history of cancer remains challenging. Diagnostic evaluation may be prolonged owing to difficulties in distinguishing between bone metastasis and common orthopedic diseases. We hypothesized that bone metastasis due to occult cancer would be more difficult to diagnose than bone metastasis in patients with a history of cancer. Few studies exist on the difficulty of diagnosing bone metastasis in patients without a history of cancer. Therefore, we reviewed the clinical course of patients with bone metastasis between January 2011 and December 2014. Methods: We reviewed patients with bone metastasis to determine the diagnostic rate at first visit, period from symptom-onset to first visit, period from first visit to diagnosis, and presence of severe skeletal-related events at diagnosis, and compared these between 27 patients without a history of cancer (Group A) and 54 patients with a history of cancer (Group B). Results: The diagnostic rate at first visit was significantly lower (11.5% vs. 52.4%, p=0.00069), the period from first visit to diagnosis was significantly longer (median, 7 weeks vs. 3 weeks, p=0.018), and the presence of severe skeletal-related events at diagnosis was significantly higher (81.4% vs. 50.0%, p=0.05) in patients without a history of cancer compared with those with a history of cancer. Conclusions: The results of this study indicate that it is difficult to diagnose bone metastasis in patients without a history of cancer. This must be considered in the early diagnosis of bone metastasis to prevent severe skeletal-related events.

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  • Hanao Yamaguchi, Yoko Funasaka, Hidehisa Saeki
    2019 Volume 86 Issue 1 Pages 27-31
    Published: January 15, 2019
    Released: March 26, 2019
    JOURNALS FREE ACCESS

    Background: For laser therapy, darker skin types should be carefully treated, however, the precise role of melanin content, subspecies, and the heat effect of the laser has not been well studied in vivo. Methods: We generated three groups of mice that have epidermal melanocytes producing only eumelanin, dominant pheomelanin, and no melanin. Using these mice, the effect of a frequency-doubled Nd:YAG laser was studied. Results: The mouse epidermis that contained eumelanin underwent heat degeneration at a lower fluence when compared with the mouse epidermis with dominant pheomelanin. The mouse skin with no melanin did not show any degeneration of the epidermis. Conclusion: The effect of the Nd:YAG laser on the cells containing different melanin subspecies was shown to be different in an in vivo irradiation system.

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  • Yozo Sato, Namiko Taniuchi, Shota Kaburaki, Naohiro Aruga, Kaoru Kubot ...
    2019 Volume 86 Issue 1 Pages 32-37
    Published: January 15, 2019
    Released: March 26, 2019
    JOURNALS FREE ACCESS

    Background: The prevalence of chronic obstructive pulmonary disease (COPD) is 8.6% in Japan and 10% worldwide. Unfortunately, many patients with COPD are not correctly identified and appropriately educated regarding the condition. In this paper, we demonstrate that some citizens of Ebina City with symptoms suspicious for COPD, such as cough, sputum production, and shortness of breath, have undiagnosed COPD. We describe our activities to raise awareness of COPD through a 10-year campaign. Methods: From 2006 to 2015, we developed activities to raise awareness of COPD, including public lectures, utilization of pulmonary function tests, and questionnaires on subjective symptoms and knowledge of COPD. Results: Among 1,206 participants aged>40 years, COPD was suspected in 5.6%, as indicated by airway obstruction (i.e. forced expiratory volume in 1 second (FEV1)/forced vital capacity ratio (FVC) <0.70). However, most of these participants were not diagnosed with COPD. Furthermore, half of these participants had not consulted a medical institution despite demonstrating symptoms. Results of the COPD awareness questionnaire, which was administered to 1,055 people, indicated that 65% of survey respondents were unaware of COPD. Conclusions: There are individuals with symptoms suspicious for COPD who are unaware of the disease at the Plaza in Ebina City. Clinicians have a responsibility to raise public awareness of COPD and to reduce the prevalence of COPD and its associated mortality.

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Case Reports
  • Shinsaku Kanazawa, Makoto Kammori
    2019 Volume 86 Issue 1 Pages 38-42
    Published: January 15, 2019
    Released: March 26, 2019
    JOURNALS FREE ACCESS

    We present a rare case of a patient with anaplastic thyroid carcinoma (ATC) who survived for 87 months after surgery. The patient was a 71-year-old man who presented with a painful enlarged mass in the right side of his neck that rapidly enlarged over 2 months. He was diagnosed with T4a, stage IVA ATC with no distant metastasis and underwent total thyroidectomy with modified neck dissection. Although only radiation and radioactive iodine therapy were administered after surgery, he remained disease-free for 84 months. Bone metastasis occurred after 84 months, and he was treated with Lenvatinib, but he died from a decline in his general condition 3 months later. We suggest that surgery is effective for stage IVA ATC, but adjuvant therapy is necessary for long-term disease-free survival in this patient population.

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  • Takeru Kashiwada, Yuji Minegishi, Yoshinobu Saito, Tomomi Kato, Kenich ...
    2019 Volume 86 Issue 1 Pages 43-47
    Published: January 15, 2019
    Released: March 26, 2019
    JOURNALS FREE ACCESS

    Acute exacerbation of pre-existing interstitial lung disease (ILD) associated with systemic anticancer therapy is recognized as a life-threatening adverse event of lung cancer treatment. Programmed cell death 1 (PD-1) checkpoint inhibitors, such as nivolumab, often induce pneumonitis in patients with cancer; however, the tolerance and safety of nivolumab for advanced lung cancer with ILD are unclear. We report a 72-year-old patient with lung cancer with pathologically proven idiopathic pulmonary fibrosis who was treated with nivolumab. She demonstrated pneumonitis with an organized pneumonia (OP) pattern, but no acute exacerbation of ILD featuring a diffuse alveolar damage (DAD) pattern. She was successfully treated with corticosteroid therapy, and maintained good disease control after the discontinuation of nivolumab. She also showed pseudoprogression of the primary tumor, implying infiltration of T-cells into the lung. These findings suggest that T-cell activation by nivolumab treatment might not be directly associated with acute ILD exacerbation, and that treatable OP might be a major pulmonary complication of nivolumab in patients with pre-existing ILD, similar to patients without underlying ILD.

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  • Pei-Ya Chen, Yu-Hsiu Juan, Shinn-Kuang Lin
    2019 Volume 86 Issue 1 Pages 48-54
    Published: January 15, 2019
    Released: March 26, 2019
    JOURNALS FREE ACCESS

    Intracranial dural arteriovenous fistula (DAVF) with perimedullary venous drainage may cause brainstem swelling and represent a diagnostic challenge. A 66-year-old man presented to the emergency room with recurrent vertigo, minimal truncal ataxia with a wide-based gait, and a slightly impaired tandem gait. Brain magnetic resonance imaging (MRI) revealed a hyperintense lesion in the left pontomedullary area on T2-weighted images (T2WIs) with partial gadolinium enhancement, but without increased signals on diffusion-weighted images. Abnormal serpentine flow void vessels surrounding the medulla and upper cervical spinal cord were initially overlooked but discovered later. An angiogram revealed DAVF with feeders from the right occipital artery and the meningeal branch of the right distal vertebral artery with drainage into the anterior medullary venous system and the perimedullary veins. The patient underwent a successful transarterial endovascular embolization and improved gradually. A brain MRI at 3-month follow-up revealed a residual hyperintense signal on the T2WIs in the left lower medulla. Six cases of patients exhibiting DAVF with isolated unilateral brainstem swelling from the literature were reviewed. Isolated unilateral brainstem swelling due to intracranial DAVF with perimedullary venous drainage is extremely rare and might mimic a tumor on MRI. Abnormal serpentine flow void vessels on the surface of the brainstem or spinal cord are crucial diagnostic clues.

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Short Communication
  • Su Hyun Song, Hong Sang Choi, Seong Kwon Ma, Soo Wan Kim, Jong-Hee Shi ...
    2019 Volume 86 Issue 1 Pages 55-57
    Published: January 15, 2019
    Released: March 26, 2019
    JOURNALS FREE ACCESS

    The number of patients receiving peritoneal dialysis has increased worldwide. Herein, we report the first case to our knowledge of continuous ambulatory peritoneal dialysis (CAPD) peritonitis caused by Micrococcus aloeverae, which was initially reported to be caused by Micrococcus luteus in the dialysate culture report but later identified by 16S ribosomal ribonucleic acid (rRNA) gene sequencing as M. aloeverae. A 59-year-old woman visited the emergency room due to abdominal pain. She was hospitalized with CAPD peritonitis. The patient initially responded to empirical antibiotic treatment comprising intraperitoneal cefazolin (15 mg/kg/day) and ceftazidime (1 g/day); however, the leukocyte count of dialysate effluent increased again. M. luteus was isolated four times from peritoneal dialysate cultures. We treated the patient with intraperitoneal administration of vancomycin (2 g loading, followed by 1 g every 7 days) but needed to switch from CAPD to temporary hemodialysis. We analyzed the 16S rRNA sequence to confirm the exact causative organism, and the results revealed that the organism was M. aloeverae. Because M. aloeverae and M. luteus have sequence similarity, 16S rRNA sequencing is a useful method to distingush them.

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Abstracts of the 2017th Encouragement Award’s Memorial Lectures of the 85st Annual Meeting of the Medical Association of Nippon Medical School
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