Internal Medicine
Online ISSN : 1349-7235
Print ISSN : 0918-2918
ISSN-L : 0918-2918
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ORIGINAL ARTICLES
  • Kazuma Kobayashi, Shun Yamaguchi, Shinichiro Ito, Yasuhiro Torashima, ...
    2020 Volume 59 Issue 10 Pages 1239-1245
    Published: May 15, 2020
    Released: May 15, 2020
    [Advance publication] Released: February 19, 2020
    JOURNALS OPEN ACCESS

    Objective In the treatment of advanced and recurrent colorectal cancer (ARCC), FOLFOXIRI regimens have been proven to be significantly superior to FOLFIRI in terms of the progression-free survival (PFS), response rate (RR), and overall survival (OS). Furthermore, the Tribe trial showed that the RR and PFS rates in patients who received bevacizumab (Bmab) +FOLFOXIRI were superior to those in patients treated with Bmab+FOLFIRI. A phase III trial of panitumumab (Pmab) +FOLFOXIRI is currently ongoing. A modified FOLFOXIRI regimen is also widely used to reduce adverse events. In our department, we introduced modified FOLFOXIRI+α (mFOLFOXIRI+α) in 2015. The present study reviewed the efficacy and safety of mFOLFOXIRI+α.

    Methods Eligible patients were retrospectively reviewed, and their results were compared to those of patients treated with other regimens (OTHERS) (n=134) to demonstrate the efficacy of this treatment.

    Patients: Between February 2015 and November 2018, 12 patients with ARCC (male/female=6/6; average age, 60.7 years old) received mFOLFOXIRI+α (Bmab: 10, Pmab: 1, alone: 1).

    Results The median PFS in the mFOLFOXIRI+α and OTHERS groups was 565 and 322 days, respectively (p=0.0544). The RR in the mFOLFOXIRI+α and OTHERS groups was 66.7% and 31.3%, respectively (p=0.0135). The conversion rate (Conv R) in the mFOLFOXIRI+α and OTHERS groups was 50.0% and 12.7%, respectively (p=0.0007). While 58% of patients treated with FOLFOXIRI+α developed grade ≥3 leukopenia, the incidence of febrile neutropenia (FN) was only 17%. In all patients with symptoms due to the tumor burden, the symptoms subsided with mFOLFOXIRI+α treatment.

    Conclusion Based on the RR, Conv R, and symptom palliation ability, mFOLFOXIRI+α was suggested to be a viable candidate for first-line treatment for patients with ARCC, especially those with a high tumor burden.

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  • Kenichiro Mikami, Tetsu Endo, Naoya Sawada, Go Igarashi, Masayo Kimura ...
    2020 Volume 59 Issue 10 Pages 1247-1256
    Published: May 15, 2020
    Released: May 15, 2020
    [Advance publication] Released: February 26, 2020
    JOURNALS OPEN ACCESS

    Objective With the aging of society, both osteoporosis and fatty liver disease (FLD) are becoming important issues. However, the relationship between osteoporosis and FLD remains controversial. We investigated the association between bone metabolism and FLD in a Japanese community in a cross-sectional study.

    Methods A total of 1,020 participants were enrolled in a health survey. FLD was diagnosed by ultrasonography. Bone metabolism was evaluated based on bone mineral density (BMD), which was assessed using dual-energy X-ray absorptiometry, and with the bone formation index (total type I procollagen N-terminal propeptide/bone-alkaline phosphatase ratio; P1NP/BAP ratio) and the bone resorption index (crosslinked N-telopeptide of type I collagen/tartrate-resistant acid phosphatase-5b ratio; NTx/TRACP-5b ratio) calculated from serum bone turnover markers.

    Results The BMD (percentage of the young adult mean) was the same level in both male and female participants with and without FLD. Both men and women showed an age-dependent decrease in their bone formation index and bone resorption index values. Men of ≥70 years of age and women of 60-69 years of age with FLD had significantly lower bone formation index values and higher bone resorption index values. However, similar findings were not seen in women of ≥70 years of age.

    Conclusion Although the BMD levels were the same, regardless of the presence or absence of FLD, elderly participants with FLD showed decreased bone formation and increased bone resorption, with sex differences. Because our results suggest that FLD in elderly individuals is detrimental for bone metabolism, and that it leads to bone loss and osteoporosis, further studies using a cohort population are warranted.

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  • Kaori Amari, Norio Fukumori, Keizo Anzai, Shu-ichi Yamashita
    2020 Volume 59 Issue 10 Pages 1257-1265
    Published: May 15, 2020
    Released: May 15, 2020
    JOURNALS OPEN ACCESS

    Objective Acute abdominal pain (AAP) of diverse etiology is a common chief complaint of patients who present to the emergency department (ED). AAP may pose a diagnostic challenge to physicians in training. We aimed to evaluate whether or not resident trainee doctors examine patients presenting with AAP in a Japanese acute-care hospital following Kendall's diagnostic algorithm.

    Methods We conducted a retrospective medical chart review from January 2015 to December 2016.

    Patients Patients ≥50 years old who presented to the ED within 7 days of the onset of AAP who were evaluated by residents at the ED of an acute care hospital were enrolled in this study. Patients transported by ambulance and referred from other hospitals and classified as level 1 or 2 according to the Japanese version of the Canadian Triage and Acuity Scale were excluded. Data, including the clinical history, location and character of pain, and age and gender of patients as well as the level of experience of residents, were abstracted from charts. We evaluated the concordance rate between the actual diagnostic process followed by residents and Kendall's diagnostic algorithm for AAP.

    Results We analyzed 466 patients (mean age 67.6 years) in the study who were evaluated and diagnosed by 123 residents. The concordance rate between the diagnostic procedures performed by residents and those suggested by Kendall's diagnostic algorithm was 61.2%. A low concordance rate was observed among patients with peritoneal signs, shock or toxic appearance (25.0%), suggested acute coronary syndromes (ACS) (55.1%), epigastric or right upper-quadrant pain (52.8%), and left upper-quadrant pain (55.6%). Abdominal ultrasonography is one of the recommended examinations for patients with signs of peritoneal irritation, shock or toxic appearance, right lower-quadrant pain, and left upper- or lower-quadrant pain, but the rates were relatively low at 25.0%, 34.4%, 31.8%, and 26.7%, respectively.

    Conclusion Abdominal ultrasonography required by Kendall's diagnostic algorithm was not performed appropriately in patients with symptoms and signs of peritonitis, shock or toxic appearance, right lower-quadrant pain, and left upper- or lower-quadrant pain or in female patients by resident trainees. Our findings underscore the importance of providing resident doctors with focused training concerning ultrasonography by attending physicians.

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CASE REPORTS
  • Yuma Hotta, Tatsuya Kawasaki, Tomoya Kotani, Hiroshi Okada, Kanami Ike ...
    2020 Volume 59 Issue 10 Pages 1267-1270
    Published: May 15, 2020
    Released: May 15, 2020
    [Advance publication] Released: February 12, 2020
    JOURNALS OPEN ACCESS

    Familial Mediterranean fever (FMF) is an autosomal recessive hereditary disease commonly observed around the Mediterranean basin presenting as recurrent febrile episodes. We herein describe a Japanese case of genetically-confirmed FMF, in which fever was lacking during attacks. An otherwise healthy 34-year-old man presented with frequent episodes of abdominal pain, which resolved spontaneously. During the attacks, the patient was afebrile, but the inflammatory marker levels in his blood were increased. Abdominal CT demonstrated enhancement of the jejunal membrane. After the initiation of colchicine therapy, the patient experienced no attacks for more than one year. The diagnosis of FMF was confirmed by a genetic analysis.

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  • Maho Iwamoto, Takuji Gotoda, Yasuhiro Noda, Mitsuru Esaki, Mitsuhiko M ...
    2020 Volume 59 Issue 10 Pages 1271-1276
    Published: May 15, 2020
    Released: May 15, 2020
    [Advance publication] Released: February 19, 2020
    JOURNALS OPEN ACCESS

    As gastric neuroendocrine carcinoma (NEC) is a rapidly growing cancer, most cases are diagnosed at advanced stages. We herein report a 74-year-old woman with an early-stage gastric NEC whose history included endoscopic submucosal dissection treatment for three early-stage gastric cancer lesions five years prior to the current presentation. We also describe the changes observed over time. An endoscopic examination during follow-up revealed an NEC (measuring 6 mm) in the gastric vestibule, for which distal gastrectomy was performed. Four months before surgery, the carcinoma exhibited specific morphological changes and lymphovascular invasion (despite the tumor being stage 1), suggesting a high-grade NEC.

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  • Yasuyuki Chiba, Arata Fukushima, Motoki Nakao, Yuta Kobayashi, Takahir ...
    2020 Volume 59 Issue 10 Pages 1277-1281
    Published: May 15, 2020
    Released: May 15, 2020
    [Advance publication] Released: February 19, 2020
    JOURNALS OPEN ACCESS

    A 23-year-old man had progressive muscle weakness and Emery-Dreifuss muscular dystrophy (EDMD) due to a LMNA (lamin A/C) mutation. Congestive heart failure diagnosed at 19 years of age. Maximal drug treatment/cardiac resynchronization failed to improve the cardiac function. He was therefore hospitalized due to heart failure. Despite extracorporeal membrane oxygenation, he developed severe right heart dysfunction and died (multiple organ failure). A cardiac lesion's presence determines the prognosis of EDMD. While there are many arrhythmia reports, few reports on heart failure (particularly severe heart failure requiring cardiac transplantation) have been published. Right heart function monitoring and early ventricular-assist device use plus right heart support considering heart transplantation are important.

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  • Kazuya Kikutani, Junji Itai, Kohei Ota, Keigo Chosa, Yoshitaka Yamane, ...
    2020 Volume 59 Issue 10 Pages 1283-1286
    Published: May 15, 2020
    Released: May 15, 2020
    [Advance publication] Released: February 19, 2020
    JOURNALS OPEN ACCESS

    Bronchial artery aneurysms (BAA) are a rare but potentially life-threatening complications because of the massive hemothorax or hemoptysis that occurs with ruptures. A 79-year-old woman was transferred to our hospital because of the sudden onset of back pain, syncope, and subsequent hypotension. Computed tomography showed a left BAA with bilateral hemothorax and hemomediastinum. Transcatheter bronchial artery embolization failed because of the anatomical location, and she went into cardiopulmonary arrest. Cardiopulmonary resuscitation was performed with successful revival. Urgent thoracic endovascular aortic repair to cover the root of the left bronchial artery was successful, and she survived without any neurological deficits.

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  • Shota Kakehashi, Tsukasa Kamakura, Takeshi Aiba, Kengo Kusano
    2020 Volume 59 Issue 10 Pages 1287-1290
    Published: May 15, 2020
    Released: May 15, 2020
    [Advance publication] Released: February 19, 2020
    JOURNALS OPEN ACCESS

    We herein report a 47-year-old man with relapsing polychondritis who developed monomorphic ventricular tachycardia (VT). His electrocardiogram in sinus rhythm showed a coved-type pattern, and there was no evidence of structural cardiac disease; therefore, he was diagnosed with Brugada syndrome. An electrophysiological study revealed a prolonged His-ventricular interval at the baseline. Two forms of VT were induced, which were shown to be bundle branch reentrant VT. A diagnosis of Brugada syndrome should not be ruled out in patients with monomorphic VTs, especially those with conduction abnormalities.

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  • Taiki Hakozaki, Miyako Kitazono, Mikio Takamori, Takahiro Kiriu
    2020 Volume 59 Issue 10 Pages 1291-1294
    Published: May 15, 2020
    Released: May 15, 2020
    [Advance publication] Released: February 26, 2020
    JOURNALS OPEN ACCESS

    Histologic transformation has been described as an acquired mechanism of resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). We herein report the case of a woman with stage IV lung adenocarcinoma harboring EGFR exon 19 deletions who was initially treated with EGFR-TKIs; several cytotoxic chemotherapeutic regimens were used when resistance developed. A lymph node re-biopsy revealed histologic transformation of the tumor to combined small-cell lung cancer and squamous cell carcinoma with retained EGFR exon 19 deletions. Following sequential chemotherapy appropriate for transformed histology, a clinical response was achieved.

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  • Hayato Moribuchi, Rumi Sato, Shuntaro Matsushima, Masaki Tominaga, Jun ...
    2020 Volume 59 Issue 10 Pages 1295-1298
    Published: May 15, 2020
    Released: May 15, 2020
    JOURNALS OPEN ACCESS

    A 56-year-old healthy man who was a current smoker died from fulminant tracheobronchial aspergillosis despite a month of treatment with a combination of intravenous anti-fungal agents that had been started immediately after the diagnosis. This case report is important for understanding and managing fulminant Aspergillus infections in healthy subjects, although the pathogenesis and underlying pathways are still unknown.

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  • Hiroaki Aizawa, Takahiro Karasaki, Kazuhiro Nagayama, Aya Shinozaki-Us ...
    2020 Volume 59 Issue 10 Pages 1299-1302
    Published: May 15, 2020
    Released: May 15, 2020
    [Advance publication] Released: February 12, 2020
    JOURNALS OPEN ACCESS

    An 80-year-old man with a history of cutaneous squamous cell carcinoma (SCC) was referred to our department for a solitary lung nodule. The nodule was surgically resected and diagnosed as SCC. Because the lung lesion and a previous skin lesion showed similar histological findings, the origin of the lung tumor was uncertain. Next-generation sequencing using a targeted driver oncogene panel was applied for the further examination. The lung lesion was diagnosed as primary lung SCC, as the two tumors possessed distinct somatic mutations in TP53. Recent advances in clinical sequencing have enabled us to obtain an accurate diagnosis in pathologically challenging cases.

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  • Satoshi Ichikawa, Kei Saito, Noriko Fukuhara, Yuya Tanaka, Yoonha Lee, ...
    2020 Volume 59 Issue 10 Pages 1303-1308
    Published: May 15, 2020
    Released: May 15, 2020
    [Advance publication] Released: February 05, 2020
    JOURNALS OPEN ACCESS

    Acquired factor X deficiency (AFXD) is a very rare coagulation disorder. A 40-year-old man with no comorbidities suffering from a fever, malaise, and severe hemorrhagic symptoms, including massive hematuria, was emergently admitted. His platelet count was normal, but his prothrombin time and activated partial thromboplastin time were markedly prolonged, which was thought to be due to autoantibody against a coagulation factor in the common pathway. Despite severe massive hematuria resulting in transient renal failure, he was successfully treated with urgent immunosuppressive therapy. Computed tomography revealed bronchopneumonia, which improved with antibiotic administration. AFXD without evidence of amyloidosis was subsequently diagnosed.

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  • Kentaro Ohta, Tetsuo Ozawa, Hidehiko Fujinaka, Kiyoe Goto, Takashi Nak ...
    2020 Volume 59 Issue 10 Pages 1309-1313
    Published: May 15, 2020
    Released: May 15, 2020
    [Advance publication] Released: February 26, 2020
    JOURNALS OPEN ACCESS

    Homozygous or compound heterozygous mutations in the high-temperature requirement A serine protease 1 gene (HTRA1) cause cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy, a very rare hereditary cerebral small-vessel disease (SVD). Recently, the relationship between some heterozygous HTRA1 mutations, most of which are missense, and the occurrence of cerebral SVD has been reported. We herein report a patient with cerebral SVD carrying a heterozygous nonsense p.R302X mutation in HTRA1. This patient had a family history of cerebral infarction. This report suggests that a heterozygous p.R302X mutation in HTRA1 causes an autosomal dominant cerebral SVD.

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  • Makiko Yashiro Furuya, Hiroshi Watanabe, Shuzo Sato, Yuya Fujita, Jump ...
    2020 Volume 59 Issue 10 Pages 1315-1321
    Published: May 15, 2020
    Released: May 15, 2020
    JOURNALS OPEN ACCESS

    We herein report a patient with mixed connective tissue disease (MCTD) who had been stable for years but suddenly developed thrombotic thrombocytopenic purpura (TTP). The patient showed a clinical pentad of signs of TTP, low activity of ADAMTS13, and positivity of anti-ADAMTS13 antibodies. She did not respond to plasma exchange or steroid therapy and died five days after admission. An autopsy revealed microthrombi in the brain, heart, kidney, adrenal glands, esophageal submucosa, and bone marrow as well as diffuse alveolar hemorrhaging. Physicians should bear in mind that TTP can occur in MCTD patients regardless of disease activity.

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  • Kayo Ishii, Takahiro Mizuuchi, Yusuke Yamamoto, Hiroaki Mori, Mayu Tag ...
    2020 Volume 59 Issue 10 Pages 1323-1330
    Published: May 15, 2020
    Released: May 15, 2020
    [Advance publication] Released: February 26, 2020
    JOURNALS OPEN ACCESS

    We describe a case of eosinophilic temporal arteritis in a 61-year-old woman with hypereosinophilic syndrome, who developed subcutaneous nodules in the temporal areas and digital cyanosis with small nodules on the sides of her fingers. Ultrasound revealed occlusion and corkscrew-like changes of the temporal and digital arteries, respectively. Temporal artery biopsy revealed eosinophilic vasculitis without giant cell formation. Angiography showed occlusion of the ulnar and digital arteries. Administration of low-dose corticosteroid improved the temporal artery swelling and digital cyanosis. More reports of similar cases are required to characterize this type of non-giant cell eosinophilic vasculitis that affects the peripheral arteries.

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