VOLUME 83 NUMBER 4 November 2021

Current Issue

ISSN 2186-3326
(Online ISSN)
ISSN 0027-7622
(Print ISSN--v.72no.3/4)

Impact Factor(2020)
 1.131

INVITED REVIEW ARTICLE

Proposal for personalized treatment of early glottic cancer with radiation therapy

Yoshiyuki Itoh and Tamami Ono
pg(s) 663 - 668

<Abstract> - < PDF >

The preservation of both the organ and its function is important for the treatment of early stage glottic cancer, and radiation therapy is an important and useful option. However, treatment with radiation therapy alone is insufficient. Therefore, to improve the local control rate even for early stage glottic cancer, attempts have been made to individualize treatment with radiation therapy (±chemotherapy) based on T stage and morphological characteristics. This individualized treatment greatly improved the local control rate for early glottic cancer. In the future, more suitable individualization can be achieved by investigating the radiosensitivity of biomarkers using biopsy materials before radiation therapy, in addition to T stage and morphological characteristics. Currently, many biomarkers are being investigated; however, appropriate biomarkers for predicting local control remain unknown.

INVITED NOTE

Reconsideration of medical treatment and care for older adults

Toshihiko Wakabayashi
pg(s) 669 - 671

<Abstract> - < PDF >

The advance care directive is a device for deciding one’s own end-of-life care by giving directions on terminal care in advance. A family discussion in the field about these documents is essential to decide the best management measures.

SYSTEMATIC REVIEW ARTICLE

Efficacy and safety of cyclooxygenase 2 inhibitors for desmoid tumor management: a systematic review

Makoto Emori, Yoshihiro Matsumoto, Yasutaka Murahashi, Masahiro Yoshida and Yoshihiro Nishida
pg(s) 673 - 681

<Abstract> - < PDF >

The efficacy and safety of cyclooxygenase 2 (COX2) inhibitors for the treatment of desmoid-type fibromatosis (DF) are unclear. Therefore, we systematically reviewed related literature to assess the efficacy and safety of COX2 inhibitors for DF treatment. We searched pertinent literature between January 1999 and August 2017 to identify relevant studies using the keywords “Fibromatosis, aggressive” and “Cyclooxygenase inhibitors.” Thereafter, we screened and determined the quality of the studies using the Grading of Recommendations Assessment, Development, and Evaluation system and extracted the article data. The critical outcomes selected were the efficacy and adverse effects of COX2 inhibitors. Efficacy was evaluated in terms of clinical benefit when patients showed complete response, partial response, and stable disease. Thirty-one articles were identified from the database search, and one was identified through the reviewers’ manual search. Finally, we retrieved six studies, including three case reports, comprising 89 patients after the first and second screenings. Fifty-three patients were excluded because three studies were reported from the same institution; hence, in total, 36 patients were included. Clinical benefit was noted in 64% of the patients. Three adverse effects were identified from the records of the six extracted studies. The strategy of watchful waiting using COX2 inhibitors with few side effects is weakly recommended for DF, especially DF patients with pain.

ORIGINAL PAPERS

S-1 facilitates canerpaturev (C-REV)-induced antitumor efficacy in a triple-negative breast cancer model

Noriyuki Miyajima, Ibrahim Ragab Eissa, Mohamed Abdelmoneim, Yoshinori Naoe, Toru Ichinose, Shigeru Matsumura, Itzel Bustos-Villalobos, Nobuaki Mukoyama, Daishi Morimoto, Masahiro Shibata, Dai Takeuchi, Nobuyuki Tsunoda, Toyone Kikumori, Maki Tanaka, Yasuhiro Kodera and Hideki Kasuya
pg(s) 683 - 696

<Abstract> - < PDF >

Canerpaturev (C-REV) is a highly attenuated, replication-competent, mutant strain of oncolytic herpes simplex virus type 1 that may be an effective new cancer treatment option. S-1, an oral formulation containing the 5-fluorouracil (5-FU) prodrug tegafur and the two enzyme modulators gimeracil and oteracil, is used as a key chemotherapeutic agent for metastatic recurrent breast cancer. Although the antitumor effects of oncolytic viruses combined with 5-FU in vivo have been reported, the detailed mechanisms are unknown. Here, we investigated the antitumor mechanism of the combination of C-REV and S-1 in triple-negative breast cancer (TNBC) in the context of tumor immunity. The combined effect of C-REV and S-1 was evaluated in a bilateral tumor model of murine TNBC 4T1 in vivo. S-1 enhanced the TNBC growth inhibitory effects of C-REV, and decreased the number of tumor-infiltrating, myeloid-derived suppressor cells (MDSCs), which suppress both innate and adaptive immune responses. Moreover, C-REV alone and in combination with S-1 significantly increased the number of CD8+ T cells in the tumor and the production of interferon γ (IFNγ) from these cells. Our findings indicate that C-REV suppresses TNBC tumor growth by inducing the expansion of effector CD8+ T cell subsets in tumors in which S-1 can inhibit MDSC function. Our study suggests that MDSCs may be an important cellular target for breast cancer treatment. The combination of C-REV and S-1 is a new approach that might be directly translated into future clinical trials against TNBC.
Editors' Choice
Prevalence of acute coronary syndrome during the pandemic of COVID-19 in the Tokai Region of Japan

Nobutaka Kudo, Akihito Tanaka, Hideki Ishii, Yusuke Uemura, Kensuke Takagi, Makoto Iwama, Ruka Yoshida, Taiki Ohashi, Hideki Kawai, Yosuke Negishi, Norio Umemoto, Miho Tanaka, Masato Watarai, Naoki Yoshioka, Itsuro Morishima, Toshiyuki Noda, Yukihiko Yoshida, Yosuke Tatami, Takashi Muramatsu, Toshikazu Tanaka, Hiroshi Tashiro, Yasunobu Takada, Hideo Izawa, Eiichi Watanabe and Toyoaki Murohara
pg(s) 697 - 703

<Abstract> - < PDF >

The outbreak of coronavirus disease 19 (COVID-19) has had a great impact on medical care. During the COVID-19 pandemic, the rate of hospital admissions has been lower and the rate of in-hospital mortality has been higher in patients with acute coronary syndrome (ACS) in Western countries. However, in Japan, it is unknown whether the COVID-19 pandemic has affected the incidence of ACS. In the study, eleven hospitals in the Tokai region participated. Among enrolled hospital, we compared the incidence of ACS during the COVID-19 pandemic (April and May, 2020) with that in equivalent months in the preceding year as the control. During the study period; April and May 2020, 248 patients with ACS were admitted. Compared to April and May 2019, a decline of 8.1% [95% confidence interval (CI) 5.2–12.1; P = 0.33] in admissions for ACS was observed between April and May 2020. There was no significant difference in the strategy for revascularization and in-hospital deaths between 2019 and 2020. In conclusion, the rate of admission for ACS slightly decreased during the COVID-19 pandemic, compared to the same months in the preceding year. Moreover, degeneration of therapeutic procedures for ACS did not occur.
Perception of feeling cold in the bedroom and sleep quality

Odgerel Chimed-Ochir, Shintaro Ando, Shuzo Murakami, Tatsuhiko Kubo, Tomohiro Ishimaru, Yoshihisa Fujino and Toshiharu Ikaga
pg(s) 705 - 714

<Abstract> - < PDF >

Sleep disorders are drawing the attention of both medical and public health concern worldwide. In Japan, research suggests that one fifth of adults do not receive appropriate sleep and 40% of adults sleep less than 6 hours a day, and sleep rates are decreasing further year by year. Many studies show that cold indoor environments negatively affect sleep comfort and quality. Whereas these studies have focused on the effects of low bedroom temperature, few studies have focused on the effect of perception of coldness. Indoor temperature is typically much lower in Japan than in other countries. Therefore, the current study aimed to identify the effect of perception of bedroom coldness on sleep quality among Japanese adults. After controlling for covariates of age, presence of current disease and pain, smoking and consumption of alcohol (Model 1), participants who sometimes, often or always felt cold in the bedroom exhibited 0.57 (95% CI=0.32–0.83, p=<.0001), 1.08 (95% CI=0.82–1.35, p<.0001) or 2.25 (95% CI=1.83–2.67, p<.0001) higher PSQI scores compared to the group which didn’t feel cold in bedroom. Our findings suggest keeping the bedroom thermal environment above a minimum limit as recommended by the World Health Organization or other organization during colder, winter nights when feeling cold during sleep. Additional deficiencies in the housing infrastructure, air quality issues due to the use of a heater, and micro bed environment need to be holistically addressed. Sleep quality can be improved by certain level via providing thermally comfortable sleeping environment.
How has the COVID-19 pandemic affected gastrointestinal surgery for malignancies and surgical infections?

Yusuke Ishibashi, Hironori Tsujimoto, Hidekazu Sugasawa, Satsuki Mochizuki, Koichi Okamoto, Yoshiki Kajiwara, Eiji Shinto, Risa Takahata, Minako Kobayashi, Yuji Fujikura, Kazuo Hase, Yoji Kishi and Hideki Ueno
pg(s) 715 - 725

<Abstract> - < PDF >

The coronavirus disease 2019 (COVID-19) pandemic has affected infection control and prevention measures. We investigated the impact of the COVID-19 pandemic on postoperative infections and infection control measures in patients underwent gastrointestinal surgery for malignancies. We retrospectively evaluated changes in clinicopathological features, frequency of alcohol-based hand sanitizer use, frequency of postoperative complications, and microbial findings among our patients in February–May in 2019 (Control group) and 2020 (Pandemic group), respectively. Surgical resection in pathological stage III or IV patients was more frequently performed in the Pandemic group than in the Control group (P = 0.02). The total length of hospitalization and preoperative hospitalization was significantly shorter in the Pandemic group (P = 0.01 and P = 0.008, respectively). During the pandemic, hand sanitizer was used by a patients for an average of 14.9±3.0 times/day during the pandemic as opposed to 9.6±3.0 times/day in 2019 (p<0.0001). Superficial surgical site infection and infectious colitis occurred less frequently during the pandemic (P = 0.04 and P = 0.0002, respectively). In Pandemic group, Enterobacter, Haemophilus, and Candida were significantly decreased in microbiological cultures (P < 0.05, P < 0.05, P = 0.02, respectively) compared with Control group. Furthermore, a significant decrease in Streptococcus from drainage cultures was observed in the Pandemic group (P < 0.05). During the COVID-19 pandemic, a decrease in nosocomial infections was observed in the presence of an increase in alcohol-based hand sanitizer use.
Health care seeking behaviors regarding maternal care and the associated factors among married women in Naung Cho Township, Myanmar

Su Yi Toe, Michiyo Higuchi, San San Htay and Nobuyuki Hamajima
pg(s) 727 - 740

<Abstract> - < PDF >

The aim of this study was to find associated factors with maternal health care seeking behaviors in a rural area in Myanmar. Married women who had delivered during the previous 12 months in Naung Cho Township were targeted and were sampled by three-stage sampling. Face-to-face interviews were performed using a structured questionnaire. The Poisson regression was used to find adjusted risk ratios (aRR) of each of two health care seeking behaviors for each of the investigated explanatory variables. Women whose husband had secondary education or above were at less risk of not having regular antenatal care (ANC) than those whose husband had only primary school level education (aRR=0.57, 95%CI: 0.34–0.95). Compared with primigravid women, aRR of not having regular ANC for those with two to four pregnancies was 1.52 (95% CI: 1.13–2.05) and 1.62 (95% CI: 1.11–2.35) for those with five or more pregnancies. Respondents who had secondary education or above and women who had married at age 20 or older showed a significantly lower risk of giving birth without skilled birth attendant (SBA) than those less educated and those who married at a younger age; aRR=0.54 (95% CI: 0.33–0.89) and aRR=0.72 (95% CI: 0.52–0.99), respectively. Own and husband’s education, the number of previous pregnancies, and marriage age were found as associated factors of maternal health seeking behaviors. Health education programs about the advantages of regular ANC and the importance of delivery with an SBA should be provided with married women, particularly targeting multigravida women, while improving access to and quality of maternal health care services.
Hypoalbuminemia is related to endothelial dysfunction resulting from oxidative stress in parturients with preeclampsia

Takuya Saitou, Kazushi Watanabe, Hiroyuki Kinoshita, Ai Iwasaki, Yuki Owaki, Hiroshi Matsushita and Akihiko Wakatsuki
pg(s) 741 - 748

<Abstract> - < PDF >

Serum albumin levels are inversely related with oxidative stress, but positively related with endothelial function, in pregnant women. However, it is unclear whether hypoalbuminemia in pregnant women with preeclampsia (PE) increases the production of oxygen-derived free radicals and impacts endothelial function. The present study aimed to assess the relationship between serum albumin, oxidative stress, and endothelial dysfunction in pregnant women with PE. A total of 75 women with control pregnancy (Control group, n = 30), PE (PE group, n = 24), or gestational hypertension (GH) (GH group, n = 21) were enrolled. We assessed serum albumin levels, diacron-reactive oxygen metabolites (d-ROMs) as an oxygen-derived free radical marker, and flow-mediated dilation (FMD) as a readout for vascular endothelial function during the gestational period and at one month after delivery. During the gestational period, FMD was lower, but d-ROM levels were higher, in the PE and GH groups compared with the Control group. Serum albumin levels were lower in the PE group compared with the Control and GH groups. d-ROM levels were inversely correlated with serum albumin levels (r = –0.54, p < 0.05) and FMD (r = –0.56, p < 0.05) in the PE group, and negatively correlated with FMD, but not serum albumin levels, in the GH group. Serum levels of d-ROMs and albumin, as well as FMD, were similar between groups after delivery. Our findings suggest that reduced serum albumin levels enhance the production of oxygen-derived free radicals, resulting in impaired maternal vascular endothelial function in parturients with PE.
Factors associated with severe dengue in Savannakhet Province, Lao People’s Democratic Republic

Phetvilay Senavong, Eiko Yamamoto, Phouvilay Keomoungkhoune, Nouda Prasith, Virasack Somoulay, Tetsuyoshi Kariya, Yu Mon Saw, Tiengkham Pongvongsa and Nobuyuki Hamajima
pg(s) 749 - 763

<Abstract> - < PDF >

This study aimed to describe the socio-demographic and clinical characteristics of dengue inpatients at a provincial hospital, and to identify factors associated with severe dengue. This is a retrospective study involving 402 dengue patients admitted to the Savannakhet Provincial Hospital, Lao People’s Democratic Republic (Lao PDR), between January 2018 and April 2019. Socio-demographic factors, clinical signs and laboratory data on admission, final diagnosis, use of health care services before admission, admission date, and hospitalization period were collected from patient records. The number of dengue inpatients was higher in the rainy season than in the dry season. Of the 402 patients, 205 patients (51.0%) were finally diagnosed with severe dengue. Children aged <15 years had more symptoms, higher proportion of severe dengue (69.8% vs. 35.9%), and longer hospitalization (3.5 days vs. 3.0 days) than adults aged ≥15 years. In multivariable analyses, factors associated with severe dengue were nausea on admission (adjusted odds ratio=3.57, 95% CI=1.05–12.09, P=0.04) in children and persistent vomiting on admission (adjusted odds ratio=3.82, 95% CI=1.23–11.92, P=0.02) in adults. In adults, the creatinine level on admission was significantly higher in patients with a final diagnosis of severe dengue compared to the others. The proportion of severe dengue in our study was higher than that in other countries. Nausea and persistent vomiting on admission were suggested to be predictive factors for severe dengue. To reduce the incidence of severe dengue in Lao PDR, improvements in access to health care, referral system, and training of health care workers are needed.
Editors' Choice
Long-term outcomes of the partial splenectomy for hypersplenism after portoenterostomy of patients with biliary atresia

Takahisa Tainaka, Akinari Hinoki, Yujiro Tanaka, Chiyoe Shirota, Wataru Sumida, Kazuki Yokota, Satoshi Makita, Kazuo Oshima, Hizuru Amano, Aitaro Takimoto, Yoko Kano and Hiroo Uchida
pg(s) 765 - 771

<Abstract> - < PDF >

Massive splenomegaly and hypersplenism in patients with biliary atresia after Kasai portoenterostomy were treated with partial splenic embolization or total splenectomy. We performed partial splenectomy to reduce the complications of partial splenic embolization and avoid overwhelming post-splenectomy infection. This study aimed to evaluate the long-term effects of partial splenectomy for hypersplenism on postoperative liver and spleen function in patients with biliary atresia. Among jaundice-free patients with biliary atresia who underwent Kasai portoenterostomy between January 1992 and December 2012, 15 underwent partial splenectomy for massive splenomegaly and hypersplenism at our institution. Changes in the laboratory data 10 years post partial splenectomy were retrospectively investigated, and these along with the latest data were measured. A total of four patients (27%) required living-donor liver transplantation after partial splenectomy, a proportion similar to those who did not undergo partial splenectomy. Compared to the preoperative baseline, the platelet counts were significantly higher at 1 and 3 years after surgery (p < 0.05). Aspartic aminotransferase-to-platelet ratio index was significantly lower at 1, 7, and 10 years after partial splenectomy (p < 0.05). No further surgeries were required for hypersplenism after partial splenectomy over 10 years, and there were no cases of overwhelming post-splenectomy infection after partial splenectomy. Partial splenectomy is safe and effective for the treatment of hypersplenism with biliary atresia over a long time period. It could be considered as an alternative to partial splenic embolization as it can suppress hypersplenism for a long time and induces fewer postoperative complications.
Is area under the curve the best parameter for carboplatin induced emetic risk stratification?

Sachiko Ozone, Kazuya Ichikawa, Masahiro Morise, Akira Matsui, Fumie Kinoshita, Reiko Matsuzawa, Junji Koyama, Ichidai Tanaka and Naozumi Hashimoto
pg(s) 773 - 785

<Abstract> - < PDF >

Carboplatin (CBDCA)-induced emetic risk is currently classified on the basis of CBDCA-area under the curve (CBDCA-AUC). We investigated the utility of three CBDCA dosage parameters for predicting emesis by CBDCA. Patients with thoracic cancer treated with CBDCA were included. The endpoints were complete response (CR) and total control (TC). CR was defined as no vomiting and no use of rescue medication during the overall assessment period, whereas TC was defined as no vomiting, nausea, nor use of rescue medication during the overall assessment period. The parameters of CBDCA were defined as follows: (1) CBDCA-AUC; (2) CBDCA/body surface area (BSA): the administered dose of CBDCA per body surface area (mg/m2); and (3) total CBDCA/body: the total administered dose of CBDCA (mg). Eighty-five patients were evaluated. The median CBDCA/BSA but not CBDCA-AUC was higher in patients with non-CR compared to those with CR. Receiver operating characteristic curve analysis revealed that the AUC of CBDCA/BSA for predicting non-CR was higher than that of CBDCA-AUC. CBDCA/BSA shows greater potential for predicting CBDCA-induced emetic risk compared with CBDCA-AUC, which is the parameter in current antiemetic guidelines.
Split-dose low-volume polyethylene glycol is non-inferior but less preferred compared with same-day bowel preparation for afternoon colonoscopy

Masahiro Tajika, Tsutomu Tanaka, Makoto Ishihara, Yutaka Hirayama, Sachiyo Onishi, Nobumasa Mizuno, Takamichi Kuwahara, Nozomi Okuno, Shinpei Matsumoto, Kazuhiro Toriyama, Masahiro Obata, Yusuke Kurita, Shinya Kondo, Kazuo Hara, Vikram Bhatia, Masahiko Ando and Yasumasa Niwa
pg(s) 787 - 799

<Abstract> - < PDF >

Currently, the same-day polyethylene glycol-electrolyte lavage solution (PEG-ELS) regimen is particularly recommended for afternoon colonoscopy as an alternative to the split-dose regimen in western countries. However, in Japan, the split-dose regimen has never been used as a standard colonoscopy preparation regimen. The aim of this study was to compare the efficacy and tolerability of split-dose PEG containing ascorbic acid (ASC) with same-day single dose PEG-ASC in Japan. This was a single-blinded, non-inferiority, two-center, randomized, controlled study. In-hospital patients were randomized to the same-day regimen or the split regimen using a web-based registry system. The same-day group was instructed to take 5 mL of sodium picosulfate in the evening, and on the day of the colonoscopy, they took 1.5 L of PEG-ASC. The split group was instructed to take 1 L of PEG-ASC before the day of colonoscopy, followed by another 1 L of PEG-ASC on the day of colonoscopy. Bowel cleansing was evaluated by the Boston Bowel Preparation Scale. A total of 153 patients were randomized to either the same-day group (n=78, males 60.0%, mean age 62.7 years) or the split group (n=75, 61.3%, 61.9 years). The rates of successful bowel cleansing were 83.3% in the same-day group vs. 92.0% (83.4%–97.0%) in the split group, P=0.10). No serious adverse events occurred in the study population. However, more patients in the same-day group were willing to repeat the same preparation regimen (P<0.001). The split-dose regimen was not inferior to the same-day regimen with respect to the efficacy of bowel preparation, but the patients preferred the same-day regimen.
Evaluation of predictive factors related to the presence or absence of supplemental oxygen therapy and comparison of physical functions after video-assisted thoracic surgery

Kohji Iwai, Ryo Komada, Yasuhiko Ohshio and Jun Hanaoka
pg(s) 801 - 810

<Abstract> - < PDF >

We performed a retrospective study of 102 individuals to evaluate predictive factors for needing supplemental oxygen therapy following video-assisted thoracic surgery (VATS) and to compare patients’ physical functions before and after surgery. Prior to surgery, we evaluated quadriceps torque, 6-minute walk distance (6MWD), timed up and go test, and grip strength. During the 6MWD, patients’ oxygen saturation was recorded every minute. Quadriceps torque and 6MWD were evaluated again following surgery. The indication for supplemental oxygen therapy was determined based on desaturation (<85%) during the 6MWD in room air. A total of 14 patients needed oxygen therapy at discharge (group A), while 88 patients did not need oxygen therapy (group B). In group A, the postoperative 6MWD was repeated with supplemental oxygen. Compared with the same parameters in group B, in group A the percentage diffusing capacity for carbon monoxide was significantly lower (p=0.011), while a history of smoking (p=0.016), exercise-induced hypoxemia (EIH, p<0.001), chronic obstructive pulmonary disease (p<0.001), and interstitial pneumonia (p=0.008) were significantly higher. Logistic regression analysis showed that EIH was an independent risk factor for requiring supplemental oxygen therapy following surgery (odds ratio: 46.2, 95% CI: 9–237.1; p<0.001). In group A, patients’ minimum oxygen saturation was significantly improved by oxygen administration (83.4±3.4 vs. 87.7±3.3, p=0.002), but there was no difference in walking distance (359.5±64.2 vs. 353.6±41.6, p=0.482). Our data indicate that patients should be preoperatively evaluated to predict postoperative hypoxemia and that this evaluation could complement the prediction of postoperative need for oxygen therapy.
Poor local control of ulcerative T1 glottic cancer treated with 2.25-Gy per fraction radiotherapy

Yumi Oie, Yoshiyuki Itoh, Mariko Kawamura, Yuuki Takase, Takayuki Murao, Shunichi Ishihara, Yoshihito Nomoto, Naoki Hirasawa, Akiko Asano, Kouji Yamakawa, Junji Ito, Fumie Kinoshita and Shinji Naganawa
pg(s) 811 - 825

<Abstract> - < PDF >

The Tokai Study Group for Therapeutic Radiology and Oncology (TOSTRO) started managing T1 glottic cancer using 2.25 Gy/fraction radiotherapy in 2011. The aim was to evaluate the local control (LC) rate and toxicity with 2.25-Gy radiotherapy in clinical practice and identify prognostic factors.The eligibility criteria were T1 glottic squamous cell carcinoma patients with age ≥20 years, treated with 2.25 Gy/fraction without chemotherapy between 2011 and 2017. LC rates were evaluated based on age, performance status, sex, T-category, tumor type (ulcerative or non-ulcerative), presence of anterior commissure invasion, tumor size, X-ray beam energy, and overall treatment time. Acute and late adverse events were evaluated using CTCAE version 4.0. A total of 202 patients were enrolled. The median follow-up period was 34.2 months. The 2- and 4-year LC rates were 93.8% and 93.1%, respectively. There was a significant difference in the LC rate between non-ulcerative type and ulcerative type (95.2% vs. 74.1% at 2 years, 94.4% vs. 74.1% at 4 years; p = 0.01). On univariate analysis, only tumor type was significantly correlated with a poor LC rate (hazard ratio 4.3; 95% confidence interval 1.2–15.4; p = 0.03). Acute grade 3 adverse events occurred in 17 patients. However, no late adverse events of grade 3 or higher have occurred to date. T1 glottic cancer treatment outcomes using hypofractionated radiotherapy with 2.25 Gy/fraction in clinical practice were comparable to previously reported results. However, ulcerative type tumor was associated with a poor LC rate.
Phase Ib study on the humanized anti-CCR4 antibody, KW-0761, in advanced solid tumors

Takuro Saito, Koji Kurose, Takashi Kojima, Takeru Funakoshi, Eiichi Sato, Hiroyoshi Nishikawa, Jun Nakajima, Yasuyuki Seto, Kazuhiro Kakimi, Shinsuke Iida, Yuichiro Doki, Mikio Oka, Ryuzo Ueda and Hisashi Wada
pg(s) 827 - 840

<Abstract> - < PDF >

Tregs infiltrate tumors and inhibit antitumor immunity. KW-0761 (Mogamulizumab) is a humanized anti-CCR4 monoclonal antibody that could eliminate activated Tregs with high immunosuppressive activity that express CCR4. In this phase Ib trial, KW-0761 was used as a cancer immunotherapeutic reagent to deplete Tregs in patients with advanced or recurrent solid CCR4-negative tumors. Thirty-nine patients with solid cancer were treated with KW-0761 at a dose of 0.1 or 1.0 mg/kg. The safety, clinical responses, and effects of Treg depletion were analyzed. Any grade and grade 3–4 treatment-related adverse events (AEs) were observed in 36 (92%) and 14 (36%) out of 39 patients, respectively. All treatment-related AEs were manageable. One and 5 patients achieved a partial response and stable disease, respectively, during treatment and were long survivors. The efficient depletion of Treg in peripheral blood was confirmed in both cohorts. Therefore, the administration of KW-0761 was safe, resulting in the depletion of Tregs in peripheral blood and potential immune responses in patients with solid cancer. The combined use of KW-0761 to deplete Tregs and other immunotherapies is a promising approach to augment immune responses.

SHORT COMMUNICATIONS

Relationship of frequency of participation in a physical checkup and physical fitness in middle-aged and elderly people: the Yakumo study

Kazuyoshi Kobayashi, Kei Ando, Hiroaki Nakashima, Masaaki Machino, Shunsuke Kanbara, Sadayuki Ito, Taro Inoue, Hidetoshi Yamaguchi, Hiroyuki Koshimizu, Naoki Segi, Yukiharu Hasegawa and Shiro Imagama
pg(s) 841 - 850

<Abstract> - < PDF >

An annual physical checkup is provided as part of the long-term Yakumo study. The checkup is voluntary and there is variation in the frequency of participation. The aim of this study was to examine relationship of physical fitness with frequency of participation in this checkup. The subjects had all attended at least one annual physical checkup from 2006 to 2018. Data from 1,804 initial checkups were used for analysis. At the checkups, age, gender, height, weight, body mass index (BMI), and bone mineral density (BMD) were recorded, and physical activity was measured. The average number of physical checkups per participant for 13 years was 2.4 (1–13). Daily exercise habits were found to be significantly associated with higher participation in physical checkups. Furthermore, between groups with low (1–5 times; <90th percentile of participants) and high (≥6 times) participation, weight and BMI were significantly higher, and BMD, grip strength, 10-m gait time, back muscle strength, and two-step test were all significantly lower in the group with lower frequency of participation in the checkup. In conclusions, our results show that frequency of participation in a voluntary annual physical checkup is significantly associated with physical fitness in middle-aged and elderly people.
Relationship between use of sleep medication and accidental falls during hospitalization

Kazuyoshi Kobayashi, Kei Ando, Hiroaki Nakashima, Yusuke Suzuki, Yoshimasa Nagao and Shiro Imagama
pg(s) 851 - 860

<Abstract> - < PDF >

Falls are common in elderly patients, and prevention of fall is important for safety and for reduction of health care costs. Sleep medications are among many potential causes of fall. In this study, we examined relationship of sleep medication with fall from January 2017 to December 2017. 726 falls occurred in 442 patients, and the average age at the time of fall was 60.7 ± 23.8 years. Fall was most common in patients with neurological disease, followed by gastroenterological, ophthalmological, respiratory, and orthopedic conditions. Sleep medication was used in 223 falls (31%). Fall occurred at all times of day, but with a different distribution in patients with and without use of sleep medication. Thus, the rate of falls from 22:00 to 6:00 was significantly higher in patients using sleep medication (62% vs. 18%, p<0.01). There was also a significantly higher rate of multiple falls in patient using sleep medication (p<0.01). Zolpidem (25%, n=63), a non-benzodiazepine, was the most frequently used sleep medication, followed by brotizolam (16%, n=41) and etizolam (13%, n=32), which are both benzodiazepines. Multiple falls from 22:00 to 6:00 occurred significantly more frequently in patients using ≥2 types of sleep medications compared to one (53% vs. 17%, p<0.01). Taking multiple sleeping pills makes it easier to fall, and even drugs with a short half-life, which are considered to be safe, can cause falls at night in elderly patients. The results of this study show that careful selection of sleep medications is required to prevent fall in elderly patients.

CASE REPORTS

Piecemeal resection of aggressive vertebral hemangioma using real-time navigation-guided drilling technique

Yoshitaka Nagashima, Yusuke Nishimura, Shoichi Haimoto, Kaoru Eguchi, Takayuki Awaya, Ryo Ando, Sho Akahori, Masahito Hara and Atsushi Natsume
pg(s) 861 - 868

<Abstract> - < PDF >

Vertebral hemangiomas are the most common benign vertebral tumors and are usually asymptomatic. Aggressive subtypes of the tumor, called aggressive VHs (AVHs), can become symptomatic with extraosseous extensions and require surgical removal. We present a case of AVH in a 36-year-old man presenting with low back pain and right leg pain that persisted for three months. Imaging studies showed a Th12 vertebral tumor that extended into the spinal canal and was squeezing the spinal cord. Computed tomography (CT)-guided biopsy indicated vertebral hemangimoa. Following preoperative arterial embolization, piecemeal gross total resection was attained under navigation guidance. He was left with no neurological deficit and remained well at the 12-month postoperative folow-up. Since AVHs are benign tumor, piecemeal removal of the tumor can be selected. However, disadvantage of the approach include difficulty of making decision how much to remove the front part of the vertebral body close to thoracic descending aorta. Furthermore, when the tumor tissue is too hard to curett, manipulation in tight spaces near the spinal cord carries the risk of damaging it. Navigation-guided drill is highly helpful for real-time monitoring of ongoing tumor resection. It enables safely resection of the tumor especially in the anterior cortical surface of the vertebral body and easily resection even hard tumors. This method results in reducing residual tumor and maintaining safety resection.
A case of intraductal tubulopapillary neoplasm of the pancreas originating from the branch duct: cast in the mold sign

Ryota Horiguchi, Hiroshi Ogawa, Naoya Nagai, Yasuo Takehara, Shinji Naganawa, Yukihiro Yokoyama and Yoshie Shimoyama
pg(s) 869 - 875

<Abstract> - < PDF >

A 59-year-old man with jaundice and lower common bile duct stenosis was referred to our institution for diagnosis and treatment. Computed tomography and magnetic resonance imaging showed a well-circumscribed smoothly marginated solid mass lesion in the pancreatic head. He underwent pyloric preserving pancreatoduodenectomy. Histopathological specimen revealed that the mass was located in the dilated branch duct of the pancreatic head, and an intraductal tubulopapillary neoplasm originating from the branch pancreatic duct was diagnosed. On magnetic resonance cholangiopancreatography, the mass within the dilated duct branch in the pancreatic head was similar to a “cast in the mold” image, which we retrospectively deemed, might be reflecting the nature of this tumor,
Amyotrophic lateral sclerosis mimicking radiculopathy: a case series

Soyoung Kwak, Du Hwan Kim, Mathieu Boudier-Revéret and Min Cheol Chang
pg(s) 877 - 881

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The clinical findings of early stage amyotrophic lateral sclerosis (ALS) are similar to those of cervical or lumbar radiculopathy. In the current study, we describe 3 cases of ALS that were misdiagnosed as cervical or lumbar radiculopathy. Three patients (a 48-, a 52-, and an 80-year-old) visited our clinic due to motor weakness on either the upper or lower extremities. At other clinics or hospitals, they were diagnosed with radiculopathy due to herniated lumbar disc or cervical foraminal stenosis. The motor weakness in these patients was ipsilateral or bilateral but dominant on one side. Sensory deficits or bulbar symptoms were not observed. Of the 3 patients, 2 had neuropathic pain, but it was not dermatome related. We conducted an electrodiagnostic test and observed a low amplitude of compound motor action potential on the af- fected nerve and positive sharp waves on muscles of involved segments, including thoracic paraspinalis. All the patients were diagnosed with probable laboratory-supported ALS or possible ALS based on the established diagnostic criteria (El Escorial Criteria). In the present study, we showed three cases of ALS that were misdiagnosed as radiculopathy. Our study would be helpful for early and accurate diagnosis of patients with ALS.
A patient with mild respiratory COVID-19 infection who developed bilateral non-hemorrhagic adrenal infarction

Yuki Asano, Tomomichi Koshi, Asami Sano, Takashi Maruno, Makoto Kosaka, Yoshitaka Yamazaki, Ako Oiwa and Yutaka Nishii
pg(s) 883 - 891

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A 76-year-old woman was admitted to the emergency room of Nagano Municipal Hospital with the complain of severe back pain. Chest and abdominal enhanced computed tomography scans showed bilateral adrenal infarction and minute pulmonary nodules, but she had no respiratory symptoms. After admission, a family member of the patient was found to have been in close contact with a coronavirus disease 2019 (COVID-19) patient. Thus, polymerase chain reaction and antigen tests of severe acute respiratory syndrome coronavirus 2 were conducted, and both tests returned positive. D-dimer levels were normal on admission but increased 2 days thereafter. Anticoagulation therapy and steroid replacement were started, and the patient improved over about two weeks. One month after the onset of adrenal infarction, a rapid adrenocorticotropic hormone loading test was conducted, which revealed that the primary adrenal insufficiency due to adrenal infarction might have been caused by the COVID-19 infection. This case was rare and suggestive of adrenal infarction with COVID-19, which usually presents at the severe stage. In patients with COVID-19, attention should be paid to the onset of thrombosis, even with mild respiratory infection. We also suggest that patients with thrombosis should be suspected of having COVID-19 even in the absence of respiratory infectious symptoms in a situation of COVID-19 epidemic.