Journal of Nippon Medical School
Online ISSN : 1347-3409
Print ISSN : 1345-4676
ISSN-L : 1345-4676
Volume 86, Issue 3
Displaying 1-8 of 8 articles from this issue
Originals
  • Akihisa Matsuda, Marina Yamada, Satoshi Matsumoto, Nobuyuki Sakurazawa ...
    2019 Volume 86 Issue 3 Pages 142-148
    Published: June 26, 2019
    Released on J-STAGE: July 10, 2019
    JOURNAL FREE ACCESS

    Background: Recent studies suggested that galectin-3 may act as a pro-inflammatory damage-associated molecular pattern. The aim of this study is to investigate the association between blood galectin-3 and postoperative complications (POC) after colorectal cancer (CRC) surgery. Methods: Blood samples were taken from 35 patients with CRC before surgery, immediately after surgery, and on postoperative days (POD) 1, 3, 5, and 7. Blood galectin-3 and interleukin-6 levels were measured by commercially available ELISA. Patients were divided into those with (POC group) and without POC (no-POC group). Results: Significantly higher galectin-3 levels were observed pre- and postoperatively in the POC group (n=10) compared with those of the no-POC group (n=25). Galectin-3 levels on POD1 showed the best predictive potential for POC (cut-off: 3.18 pg/mL, area under the curve: 0.868). Conclusions: These results indicate that increased perioperative blood galectin-3 levels may be associated with POC after CRC surgery.

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  • Kenji Takahashi, Hiroshi Nakamura, Atsushi Watanabe, Tokifumi Majima, ...
    2019 Volume 86 Issue 3 Pages 149-158
    Published: June 26, 2019
    Released on J-STAGE: July 10, 2019
    JOURNAL FREE ACCESS

    Background: Methotrexate (MTX) is still the first-choice drug for the treatment of rheumatoid arthritis (RA). In Japan, MTX doses of up to 16 mg/week were approved in 2011. In this study, we aimed to identify the gene polymorphisms that can predict therapeutic effects of MTX in Japanese patients in current clinical settings. Methods: This study involved 171 patients with RA (all Japanese nationals, age 63.5±10.0 years) who had been administered MTX. The analyzed polymorphisms included 82 single nucleotide polymorphisms (SNPs) involved in the MTX pharmacological pathway or in the pathogenesis of RA. Responders were patients who showed high sustained remission or low disease activity with MTX or conventional disease-modifying anti-rheumatic drugs (DMARDs) treatment beyond 6 months. Non-responders were patients who showed moderate or high disease activity, who were prescribed biological DMARDs. A logistic model was constructed with Responder/Non-responder as the target variable, and minor allele frequency was set as an explanatory variable. Results: None of the 82 SNPs targeted for analysis met the Bonferroni significance threshold of 6.098×10−4. However, we identified SLCO1B1 rs11045879 as an SNP that might yield significant results if the number of patients were to be increased (P=0.015). Conclusions: The rs11045879 minor allele in the SLCO1B1 gene is a potential predictor of non-responders to MTX treatment among Japanese RA patients. In future collaborative research, we will investigate whether the association with SLCO1B1 polymorphism is significant by performing statistical analysis with a larger study population.

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  • Yasuyuki Kitagawa, Toshihiko Ito, Yoshihiro Mizuno, Yoshihiro Sudo, Yo ...
    2019 Volume 86 Issue 3 Pages 159-164
    Published: June 26, 2019
    Released on J-STAGE: July 10, 2019
    JOURNAL FREE ACCESS

    Background: Early diagnosis of bone metastasis is difficult. The aim of the present study was to determine whether symptoms related to skeletal-related events (SREs) can be used for the diagnosis of bone metastasis in the absence of screening tests. Methods: We reviewed 81 patients with bone metastasis to evaluate their SREs at diagnosis. SREs were arbitrarily classified as moderate or severe. Moderate SREs included radiation to the bone before pathological fracture or paralysis, bone surgery before pathological fracture or paralysis, and hypercalcemia without dialysis. Severe SREs included pathological fracture, spinal cord compression, and hypercalcemia necessitating dialysis. Results: The complication rates of SREs at the time the bone metastasis was diagnosed were 59.3% and 24.7% for severe and moderate SREs, respectively, and only 16.0% of cases were uncomplicated. The clinical factors that showed a significant relationship with the severity of SREs were age and history of malignancy. However, there was no significant relationship between the complication rate of total SREs and the presence or absence of a malignancy history (83.3% vs. 85.2%, respectively, p=0.83). Conclusion: The results of the present study suggest that symptoms related to SREs can be used to diagnose bone metastasis in the absence of a screening test. Bone metastasis should be diagnosed as often as possible based on symptoms related to moderate SREs and should be treated as soon as possible before patients develop severe SREs.

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  • Kei Kimizuka, Kenichi Inoue, Shigenori E. Nagai, Tsuyoshi Saito, Satok ...
    2019 Volume 86 Issue 3 Pages 165-171
    Published: June 26, 2019
    Released on J-STAGE: July 10, 2019
    JOURNAL FREE ACCESS

    Background: Fulvestrant 500 mg has been an option for endocrine therapy for advanced or recurrent breast cancer after prior endocrine treatment since November 2011 in Japan. This study aimed to clarify the effectiveness and safety of fulvestrant 500 mg in clinical settings. Methods: This was a multicenter, both prospective and retrospective, observational study of 132 postmenopausal women (median age 66) with locally advanced or metastatic breast cancer, who had been treated with fulvestrant. Information from medical records was retrospectively obtained from 9 hospitals (Saitama Breast Cancer Clinical Study Group: SBCCSG) in Saitama prefecture, Japan, from October 2012 to April 2014. The primary end point was time to treatment failure (TTF). The secondary end points were overall survival (OS), objective response rate (ORR), clinical benefit rate (CBR), and adverse events (AE) (CTCAE ver. 4). The choice of subsequent therapy after fulvestrant was also evaluated. Results: The median TTF was 6.1 months. Median OS was 28.5 months (the starting date was the first day of fulvestrant). ORR was 12.9% and CBR was 45.5%. The most common AEs were injection site reactions (9.1%). The rate of grade 3 AE was only 2.3% (3/132). The number of patients who underwent subsequent therapy after fulvestrant were 54 (55.7%) receiving chemotherapy, 42 (43.3%) receiving non-fulvestrant endocrine therapy, and 1 (1%) receiving mammalian target of rapamycin inhibitor (mTORi) + endocrine therapy (ET). Conclusion: Fulvestrant 500 mg is an effective and safe treatment for patients with advanced or recurrent breast cancer after prior endocrine treatment.

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Case Reports
  • Ichiro Okada, Junichi Inoue, Hiroshi Kato, Yuichi Koido, Nobuaki Kiriu ...
    2019 Volume 86 Issue 3 Pages 172-178
    Published: June 26, 2019
    Released on J-STAGE: July 10, 2019
    JOURNAL FREE ACCESS

    Background: Renal artery stenting is performed for renal artery injuries to preserve renal function and prevent renovascular hypertension. However, its indications are controversial and its long-term prognosis remains unknown. Here, we evaluate the characteristics and long-term outcomes of renal artery stenting for blunt renal artery injuries at our institution. Methods: We retrospectively reviewed patients with blunt renal artery injuries who had been treated with stenting over a 12-year period at our institution. Five patients (three men and two women) were included. Results: Trauma resulted from falls in three patients and motor vehicle accidents in two. All patients had experienced multiple injuries (median injury severity score, 24 [range, 16-48]; median revised trauma score, 5.9672 [4.0936-7.8408]; and median probability of survival, 0.689 [0.533-0.980]). All renal artery injuries involved stenosis because of traumatic arterial dissection or intimal tear; no cases of total occlusion were observed. No complications due to the intervention itself were observed. Although two patients developed reversible acute renal failure, none required long-term hemodialysis. One patient with renovascular hypertension was treated with antihypertensive agents for a month and subsequently became normotensive without further medication. All patients underwent postoperative computed tomography, which revealed no stent occlusion or renal atrophy. Renal scintigraphy for three patients demonstrated preserved differential renal function. All five patients survived. Conclusions: Renal artery stenting for hemodynamically stable blunt renal artery injuries with stenosis is suggested to be safe and helps in avoiding long-term hemodialysis and renovascular hypertension.

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  • Shaocheng Lyu, Qiang He
    2019 Volume 86 Issue 3 Pages 179-182
    Published: June 26, 2019
    Released on J-STAGE: July 10, 2019
    JOURNAL FREE ACCESS

    Littoral cell angioma (LCA), a rare vascular neoplasm that occurs in the spleen, is difficult to definitively diagnose preoperatively because histological examination is the only accurate means of diagnosing this condition. Thus, the preoperative diagnosis is often incorrect. Splenectomy is the appropriate treatment and can be performed laparoscopically or by open surgery depending on the size of the tumor. Here we present a case of a 38-year-old man who presented with a history of slight non-specific abdominal distension for 2 months. An abdominal CT scan showed a huge spleen measuring 35×18 cm and containing multiple lesions, the largest being 11.3×9.2 cm. The patient underwent open splenectomy and recovered well. Histological examination showed LCA of the spleen. To our knowledge, this is the largest reported LCA thus far and may advance our understanding of this condition.

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  • Masaki Miyao, Tsubasa Takahashi, Mikihiro Okusa, Makoto Kusakabe, Ryot ...
    2019 Volume 86 Issue 3 Pages 183-186
    Published: June 26, 2019
    Released on J-STAGE: July 10, 2019
    JOURNAL FREE ACCESS

    The preoperative diagnosis of cecal volvulus (CV) is rare and difficult and emergent laparotomy is frequently performed. Here, we report a case of CV that was diagnosed by preoperative computed tomography in a patient with an intellectual disability. In addition, we demonstrate that elective laparoscopic cecopexy can be performed following conservative treatment, such as the use of an ileus tube per anus.

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  • Naoko Kanda, Fumitaka Okajima
    2019 Volume 86 Issue 3 Pages 187-190
    Published: June 26, 2019
    Released on J-STAGE: July 10, 2019
    JOURNAL FREE ACCESS

    Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a serine protease that targets the low-density lipoprotein (LDL) receptor for lysosomal degradation. PCSK9 impedes the receptor-mediated clearance of LDL-cholesterol, thereby increasing serum LDL-cholesterol levels. Evolocumab, a human monoclonal antibody against PCSK9, effectively reduces serum LDL-cholesterol levels. We report the first known case of a patient who developed an atopic dermatitis (AD)-like rash during evolocumab therapy. A 43-year-old Japanese man with heterozygous familial hypercholesterolemia was treated with subcutaneous injection of 140 mg evolocumab biweekly, for 16 months. The therapy was then changed to subcutaneous injection of 420 mg evolocumab monthly. A few days after the first dose, the patient experienced pruritus and rash on his extremities. The rash worsened, while the pruritus subsided, then relapsed after the second and third doses. He had erythema and excoriation on his legs, lichenification over his popliteal fossa, xerosis on his forearms, an increased serum IgE level, and a family history of AD in his siblings. We made a provisional diagnosis of AD characterized by enhanced type 2 helper T (Th2) activity and treated him with topical corticosteroids and oral anti-histamines. His rash improved and did not relapse after the fifth dose; however, his LDL-cholesterol level increased. PCSK9 or oxidized LDL activates macrophages or dendritic cells, respectively, and enhances their activity to induce Th1 cells antagonizing Th2 cells. We hypothesized that high-dose evolocumab may suppress Th1 activity to antagonize Th2, and unmask Th2 disposition based on the patient's atopic diathesis, triggering the rash mimicking AD. Clinicians should be aware of rash development during evolocumab therapy.

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