タイトルToho J ournal of Medicine Vol. 7 No. 1 掲載論文の紹介
 別タイトルPUBLISHED ARTICLES IN THE TOHO J OURNAL OF MEDICINE Vol. 7No. 1
作成者（著者）東邦大学医学会編集委員会
公開者東邦大学医学会
発行日2021.03.01
ISSN00408670
掲載情報東邦医学会雑誌. 68(1). p.20-25.
資料種別その他
著者版フラグpublisher
メタデータのＵＲＬhttps://mylibrary.toho-u.ac.jp/webopac/TD47208208
Toho Journal of Medicine Vol. 7 No. 1 掲載論文の紹介
Advances in the Treatment of Rheumatoid Arthritis
Tanaka E, Muraoka S, Nanki T
Toho J Med 7 （1）: 1―10, 2021
Rheumatoid arthritis (RA) is characterized by synovitis, bone erosion, and cartilage destruction, which ultimately 
lead to joint destruction. The pyramidal plan, which aims to attenuate symptoms, was the standard treatment for RA. 
However, advances in therapeutic agents mean that the maintenance of remission is now a realistic treatment goal. 
Recent treatments, including methotrexate, biological disease-modifying anti-rheumatic drugs, and Janus kinase inhibi-
tors, achieve low disease activity and improve the prognosis of RA; however, not all patients exhibit favorable 
responses. Furthermore, the economic burden and adverse effects associated with these treatments have not yet been 
resolved. Therefore, the development of more effective and safer therapies is required. Advances in the treatment of 
RA have been discussed herein. 
KEYWORDS: biologics, Janus kinase inhibitors, methotrexate, rheumatoid arthritis
Comparison of the Effect of Proton Pump Inhibitors on Capecitabine and S-1 in Gastric Cancer Treatment with 
Trastuzumab; A Multi-Institutional Analysis
Kikuchi Y, Yamashita H, Fujisaki M, Yoshimoto Y, Otsuka K, Nagaoka S, Fujita S, Tokuyama J, Satodate H, 
Isobe Y, Urakami H, Mitsumori N, Seto Y, Futawatari N, Yajima S, Oshima Y, Murakami M, Igarashi Y, Shi-
mada H
Toho J Med 7 （1）: 11―19, 2021
Introduction: The effect of proton pump inhibitors on capecitabine- and S-1-based treatment for human epidermal 
growth factor receptor 2 (HER2)-positive gastric cancer is unknown. Therefore, we compared the effect of proton pump 
inhibitors between capecitabine- and S-1-based treatments for HER2-positive gastric cancer. 
Methods: In a multi-institutional study, we retrospectively analyzed the effect of proton pump inhibitors on 155 
HER2-positive advanced or recurrent gastric cancer patients who were treated with oral 5-fluorouracil (capecitabine or 
S-1) and trastuzumab. Capecitabine- and S-1-based treatments were compared in terms of the response rate and time 
to treatment failure, and the negative effects of proton pump inhibitors on the treatment response were evaluated. In 
this study, the primary endpoint was the response rate, and the secondary endpoint was time to treatment failure. 
Results: There was no significant difference in the response rate between the capecitabine- and S-1-based treat-
ments. However, in cases without proton pump inhibitor intake, the response rate significantly improved with 
capecitabine-based treatment rather than with S-1-based treatment (P = 0.046). Compared with the S-1-based treatment, 
the capecitabine-based treatment significantly prolonged the time to treatment failure (P = 0.044), including for patients 
with differentiated adenocarcinoma (P = 0.035). 
Conclusions: For HER2-positive and differentiated gastric cancer, capecitabine-based treatment may be better than 
S-1-based treatment. Proton pump inhibitors might decrease capecitabine’s effects and should be avoided to increase 
the response rate to capecitabine-based treatment. 
KEYWORDS: proton pump inhibitor, HER2-positive gastric cancer, capecitabine, S-1, trastuzumab
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Postoperative Acute Kidney Injury Associated with Anesthesia Induction in Extremely Hypertensive Patients 
Undergoing Elective Non-Cardiac Surgery
Morozumi K, Satomoto M, Hanai Y, Ochiai R, Kotake Y
Toho J Med 7 （1）: 20―28, 2021
Introduction:  Some patients exhibit extreme hypertension before anesthetic induction. Although it is important to 
avoid hypotension during anesthesia to prevent major postoperative complications, it remains unknown how anesthetic 
hypotension should be managed in patients with hypertension. Therefore, we investigated the incidence of postopera-
tive complications and their associations with low blood pressure during surgery in patients with a systolic blood pres-
sure ＞200 mmHg before anesthetic induction. 
Methods:  We assessed the incidence of postoperative acute kidney injury (AKI), myocardial infarction (MI), and isch-
emic stroke. For postoperative AKI, we investigated the duration, between intubation and surgery initiation, for which 
the patients’ mean arterial pressure (MAP) was below the threshold, and the duration from surgery initiation to the 
end of anesthesia. Based on these analyses, factors considered to be clinically associated with postoperative AKI were 
extracted and subjected to multivariate logistic regression analysis. 
Results:  In total, 274 patients were enrolled. Of these, 35 developed AKI and one experienced MI and ischemic 
stroke. The durations for which the MAP was ＜65, 70, and 75 mmHg between intubation and incision were signifi-
cantly longer in the AKI group than in the non-AKI group (P ＜ 0.01). Multivariate regression analysis revealed a sta-
tistically significant association between the duration of having a MAP ＜75 mmHg and postoperative AKI (adjusted 
odds ratio = 1.04, confidence interval=1.02-1.07, P ＜ 0.001). 
Conclusions:  In patients with extreme hypertension before anesthetic induction undergoing elective non-cardiac sur-
gery, a MAP ＜75 mmHg between intubation and incision may be an independent risk factor for postoperative AKI. 
KEYWORDS: preinduction hypertension, anesthesia, surgery, postoperative complications, acute
kidney injury
Comparison of First- and Second-Generation Drug-Eluting Stents for Bifurcation Stenting
Fujii T, Watanabe I, Nakanishi R, Amano H, Toda M, Ikeda T
Toho J Med 7 （1）: 29―38, 2021
Introduction: Percutaneous coronary intervention (PCI) for bifurcated lesions is challenging. We assessed the proce-
dural performance and clinical outcomes of first- and second-generation drug-eluting stents (DES) in bifurcation stent-
ing followed by the final kissing-balloon (FKB) technique. 
Methods: We retrospectively analyzed 192 patients (222 lesions) who underwent PCI for bifurcated lesions. In all 
cases, lesions underwent stenting, followed by FKB. Clinical outcomes were compared for the two generations―first-
generation (80 patients/88 lesions) vs. second-generation (112 patients/134 lesions). The primary endpoint was target-
lesion failure (TLF), defined as cardiac death, target-lesion revascularization or target-lesion-related stent thrombosis at 
2 years. 
Results: TLF incidence was higher for first-generation DES than for second-generation DES (15.0% vs. 2.7%; P＜0.01). 
The first-generation DES (hazard ratio ［HR］: 6.41, 95% confidence interval ［CI］: 1.75-23.5, P＜0.01) and SYNTAX score 
(HR: 1.07, 95% CI: 1.01-1.13, P ＝ 0.02) were predictors of TLF after bifurcation stenting followed by FKB. PCI for the 
left main trunk (HR: 6.22, 95% CI: 1.55-25.0, P = 0.01) and SYNTAX score (HR: 1.09, 95% CI: 1.02-1.17, P = 0.02) were 
found to be associated with increased TLF for patients who were treated with first-generation DES, but no prognostic 
factor of TLF was found for patients with second-generation DES. 
Conclusions: In bifurcation stenting followed by FKB, outcomes are better for second-generation DES than for first-
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generation DES. 
KEYWORDS: percutaneous coronary intervention, drug-eluting stent, bifurcation stenting, final kissing-balloon 
technique, target-lesion revascularization
Comparison of Cardiac Output and Stroke Volume Calculated by Pulse Wave Transit Time at the Fingertip Versus at 
the Toe
Hasegawa M, Ochiai R, Kotake Y
Toho J Med 7 （1）: 39―47, 2021
Introduction: The estimated continuous cardiac output (esCCO), which is a noninvasive way of measuring cardiac 
output, enables the measurement of vital parameters to evaluate the oxygen supply/demand balance of organs and tis-
sues. The esCCO is optimized for measurement using a fingertip pulse oximeter; however, in some instances, various 
conditions prevent attaching a probe to the fingertip. Thus, the cardiac index (esCI) and stroke volume index (esSVI) at 
the fingertip and toe were simultaneously measured and examined to determine whether the values measured at the 
toe could be used as an alternative to estimate those parameters and predict fluid responsiveness. 
Methods: In total, 31 otorhinolaryngology surgery cases under general anesthesia were examined. We statistically 
analyzed the compatibility and trending ability of the SVI and CI values between at the fingertip and toe. Further, we 
were able to examine fluid responsiveness during hypotension. These data were then used to create a receiver operat-
ing characteristic curve and determined cutoffs of stroke volume variation (SVV) at the toe in order to predict greater 
than 10% increase in esSVI at the fingertip. 
Results: As per out findings, esSVI and esCCI measured at the fingertip and toe exhibited significantly high compatibility 
and trending ability. Further, the cutoff value for greater than 10% increase in esSVI at the fingertip was toe SVV of 7.0%. 
Conclusions: esSVI and esCI measured at the toe have exhibited high compatibility and trending ability with the 
data obtained at the fingertip; concurrently, they enabled the evaluation of fluid responsiveness. We confirmed that 
even when physical limitations prevent the attachment of a pulse oximeter probe to the fingertip, the SVI and CI can 
be well estimated at the toe. 
KEYWORDS: estimated continuous cardiac output (esCCO), cardiac output, cardiac index, stroke volume index, 
stroke volume variation
LR11, an LDL Receptor Gene Superfamily Member, Represses the Norepinephrine-Induced Expression of 
Uncoupling Protein 1 in Primary Cultured Beige Adipocytes
Nakamura S, Jiang M, Oka R, Yamaguchi T, Hiruta N, Ebinuma H, Schneider W J, Tatsuno I, Bujo H
Toho J Med 7 （1）: 48―56, 2021
Introduction: The soluble form of LR11 (sLR11) inhibits thermogenesis via BMPs/TGFβ signaling pathways in adipo-
cytes. Mice lacking LR11 are protected from diet-induced obesity associated with increased browning of subcutaneous 
white adipose tissue (WAT) and hypermetabolism. However, the mechanism underlying the recruitment of beige adi-
pocytes has not been elucidated. In this paper, we have investigated the expression of LR11 in the differentiation and 
norepinephrine-induced activation of cultured beige adipocytes. 
Methods: LR11 mRNA levels were analyzed in cultured beige adipocytes differentiated from human immortalized 
adipose-derived stromal cells or from the subcutaneous WAT of wild-type (WT) and Lr11
－/－ mice. The concentrations 
of sLR11 were measured by an ELISA specific for murine sLR11. 
Results: In the course of browning adipogenesis of human stromal cells, LR11 mRNA levels decreased at the begin-
東邦医学会雑誌・2021 年 3 月
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ning and subsequently increased together with uncoupling protein (UCP) 1, β3-adrenergic receptor, lipoprotein lipase, 
and adiponectin. The LR11 transcript levels in the differentiated cells were transiently decreased by incubation with 
norepinephrine, and this change was in clear contrast to the increase of UCP1 mRNA levels. The mRNA levels of 
UCP1 in murine Lr11-/- beige adipocytes were significantly increased compared with those in WT beige adipocytes, 
regardless of norepinephrine stimulation. Finally, the amounts of sLR11 released from murine WT beige adipocytes 
were decreased by incubation with norepinephrine. 
Conclusions: LR11 potentially represses the norepinephrine-induced expression of UCP1 in differentiated beige adipo-
cytes. The sLR11-mediated repression of the key molecule in thermogenesis may be involved in the sympathetic acti-
vation of the recruitment of beige adipocytes in subcutaneous fat. 
KEYWORDS: LR11, adipogenesis, thermogenesis, UCP1, beige
Change of Plasma Ketone Bodies and Skin Gas Acetone in Hemodialysis Patients
Suzuki T, Sasaki Y, Komatsu F, Maeda T, Suzuki K, Urita Y
Toho J Med 7 （1）: 57―65, 2021
Introduction: Ketone body metabolism increases under various pathological conditions, including insulin resistance, 
inflammation, and heart failure, which are common in hemodialysis patients. This study investigated whether plasma 
ketone bodies and skin-gas acetone are useful biomarkers of metabolic conditions during hemodialysis. 
Methods: Twenty patients with end-stage renal disease undergoing maintenance dialysis for at least 9 months were 
enrolled. To measure plasma ketone body concentrations before and immediately after hemodialysis, blood samples 
were collected from the shunt vessel. Also, we measured acetone concentration in the vapors emanating from the skin. 
Results: Plasma ketone body concentrations increased 6-fold after hemodialysis, with a remarkable increase of 
β-hydroxybutyrate (BOHB) and plasma BOHB/acetoacetate ratio. Conversely, no significant change of skin-gas acetone 
concentration was observed. Therefore, no association was found between the concentration of plasma ketone bodies 
and skin-gas acetone. Increased ratio of glucose level and ketone bodies exhibited a positive correlation; however, other 
laboratory data did not. Increased ratio of plasma BOHB significantly correlated with water removal ratio. 
Conclusions: We found a significant increase in BOHB-dominant plasma ketone bodies, which significantly correlated 
with the water removal ratio, and dissociation between the changes in skin-gas acetone and plasma ketone body con-
centrations after hemodialysis. These results suggest an association between two independently reported cardiovascu-
lar risk factors, plasma BOHB concentration and fluid removal amount in hemodialysis patients. Although no 
association between skin-gas acetone and plasma ketone bodies was observed, the dissociation suggests an increase in 
ketone body synthesis during hemodialysis. 
KEYWORDS: acetone, plasma ketone body concentration, hemodialysis, end-stage renal disease, skin gas
Pain Intensity Measurement after Gynecological Laparoscopic Surgery Using the “Pain Vision
TM” System for 
the Quantitative Analysis of Perception and Pain Sensation
Katakura M, Nakaoka K, Taniguchi T, Maemura T, Morita M
Toho J Med 7 （1）: 66―72, 2021
Introduction: Postoperative analgesia is easier if the degree of pain and factors enhancing pain with each operation 
can be predicted more accurately. To assess postoperative pain after gynecological laparoscopic surgery, we evaluated 
the extent of pain before and after treatment using the visual analogue scale (VAS) and “Pain Vision
TM” system, which 
is a quantitative analyzer of sensory perception and pain. 
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Methods: In total, 33 cases of laparoscopic uterine myoma enucleation (LM group) and 41 cases of laparoscopic total 
hysterectomy (TLH group) were assessed using the VAS and “Pain Vision
TM” system. The changes in the pain degree, 
measured using “Pain Vision
TM”, were evaluated over time and examined. Briefly, to measure the pain degree, an elec-
trode is attached to the forearm, the stimulus is applied, and the current perceptual threshold and the current value of 
pain are registered. These values are then applied to the following equation: degree of pain = (pain response current - 
minimum sensing current)/minimum sensing current. 
Results: The standardized regression coefficients were 0.144 for VAS and 0.229 for Pain Degree. Importantly, these 
values were significantly different. This analysis suggests that LM is a factor that affects the values of VAS and Pain 
Degree rather than TLH. 
Conclusions: The postoperative pain was stronger in the LM group than in the TLH group. Based on these results, 
postoperative pain management should be considered separately for each surgical procedure. 
KEYWORDS: Pain Vision, post operative pain, laparoscopic surgery
Anesthetic Management and Postoperative Course of a Patient with Anti-N-Methyl-D-Aspartate Receptor 
Encephalitis Associated with Ovarian Teratoma
Kimura R, Koda K, Kimura H, Uzawa M, Sato K, Aiba Y, Ishida H, Kitamura T
Toho J Med 7 （1）: 73―77, 2021
A 32-year-old woman complained of fever, hallucinations, and seizures. Based on her symptoms and the presence of 
an ovarian tumor, anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis was suspected. Without waiting for spe-
cific antibody test results, she underwent emergency laparoscopic salpingo-oophorectomy. The patient received gen-
eral anesthesia, which was maintained with midazolam, propofol, opioids, and rocuronium. Her anesthesia recovery was 
uneventful, and she had tracheal extubation after surgery. Postoperatively, her symptoms deteriorated, despite first-
line immunotherapy using immunoglobulin, steroids, and plasmapheresis. She required respiratory support for central 
hypoventilation. As second-line immunotherapy, rituximab and cyclophosphamide were administered, resulting in 
gradual symptom improvement. Approximately five months after onset, she was discharged in an ambulatory condi-
tion. Early tumor resection, combined with immunotherapy, is recommended for anti-NMDAR encephalitis secondary 
to tumors. Since there are individual differences in the clinical courses of patients with this disease, careful periopera-
tive management is essential. 
KEYWORDS: anti-N-methyl-D-aspartate receptor encephalitis, laparoscopic salpingo-oophorectomy, anesthetic 
management, postoperative course
Radical Esophagectomy Combined with Resection of the Invaded Descending Aorta for T4 Barrett’s Esopha-
geal Carcinoma: A Case Report
Yajima S, Suzuki T, Okuma S, Fujii T, Nanami T, Oshima Y, Shiratori F, Funahashi K, Watanabe Y, Shimada 
Toho J Med 7 （1）: 78―83, 2021
A 58-year-old Japanese man was diagnosed with T4b (descending aorta) N2M1, stage IVB lower thoracic Barrett’s 
esophageal adenocarcinoma. He was initially treated with definitive chemotherapy with cisplatin and 5-fluorouracil (FP 
therapy). After one course of FP therapy, he developed renal dysfunction complications. Computed tomography 
showed no remarkable change in the main tumor and metastatic lesion. Therefore, radical esophagectomy with resec-
tion of the invaded descending aorta and removal of the solitary metastatic lesion was performed. Superior mediastinal 
東邦医学会雑誌・2021 年 3 月
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dissection, esophageal transection, and left adrenal gland removal were performed simultaneously. The patient under-
went curative resection but died of multiple hematogenous metastases 116 days postoperatively. As aortic infiltrates 
were infected, artificial blood vessel replacement was selected. Although he underwent radical esophagectomy, hema-
togenous metastases have occurred in the early postoperative period. 
KEYWORDS: Barrett’s esophageal adenocarcinoma, T4 aorta
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