VOLUME 87 NUMBER 2 May 2025
INVITED REVIEW ARTICLES
Calcineurin in cancer signaling networks
Honoka Haba, Shoma Tsubota and Midori Shimada
pg(s) 182 - 195
Calcium/calcineurin/nuclear factor of activated T-cell signaling is a vital regulator of the development and
function of immune, nervous, cardiovascular, and musculoskeletal systems. The dysregulation of calcineurin
activity has been implicated in various pathological conditions, including certain cancers, cardiac hypertrophy,
and neurodegenerative disorders. Calcineurin is highly expressed in certain cancers and stabilizes and
activates factors that promote cancer cell proliferation. Research has shown that protein dephosphorylation
by calcineurin contributes to tumor formation and progression. Thus, elucidating molecular mechanisms of
calcineurin-mediated tumorigenesis and tumor cell growth and targeting signaling pathways downstream
of calcineurin may lead to new cancer therapies. This study reviewed the multiple roles of calcineurin in
cell cycle progression and its potential as a target for cancer treatment.
Unraveling the enigma of mental disorders: a genetics-first approach and the role of mouse models based on rare disease-susceptible genome variants
Reon Kondo, Daisuke Mori, Hiroaki Wake and Norio Ozaki
pg(s) 196 - 210
Mental disorders are a major global cause of disability that involve significant disturbances in thinking,
emotional regulation, or behavior. The pathogenesis of these illnesses is complicated by their obscure nature
and lack of biological markers. A genetics-first approach has been proposed to address this complexity. This
approach associates clinical phenotypes with disease-susceptible genomic variants, such as copy number
variations and single nucleotide variants. These rare variants significantly affect disease development and
are thus crucial for assessing the effects of specific variants on disease and in determining the underlying
biological mechanisms. In particular, mouse models that reflect these variants are instrumental in defining
the causal relationships between genetic variants and disease-relevant phenotypes. Recent studies have
highlighted the importance of sensory information processing in humans and mice. Advanced technologies
that are valuable in unraveling the neural circuit mechanisms of these phenotypes include optogenetics
and in vivo 2-photon imaging. Furthermore, mouse models can guide the integration of findings from
patients and induced pluripotent stem cells, supporting a multidimensional approach to understanding the
pathophysiology of mental disorders. In this review, we briefly discuss the utility of mouse models in a
genetics-first approach to elucidate the pathophysiology of mental disorders. We also present examples of
our mouse models based on rare disease-susceptible variants.
ORIGINAL PAPERS
Long non-coding RNA taurine upregulated 1 regulates the progression of head and neck cancer
Kohei Nioka, Norihisa Ichimura, Shohei Ikutomi and Hideharu Hibi
pg(s) 211 - 219
Taurine upregulated 1 (TUG1), whose function is associated with tumor development, is a relatively
new long non-coding RNA. TUG1 is overexpressed in multiple types of cancers. However, in head and
neck squamous cell carcinoma (HNSCC), the behavior of TUG1 has not yet been completely elucidated.
Therefore, we aimed to clarify the function of TUG1 in HNSCC and develop a novel therapeutic target.
We analyzed the expression levels of TUG1 in patients with HNSCC using The Cancer Genome Atlas
dataset and human oral keratinocytes, and five HNSCC cell lines (HSC-4, Sa3, HSQ-89, SAS, and Ca9-22)
through quantitative reverse-transcription polymerase chain reaction. The biological role of TUG1 in HNSCC
was investigated using cell growth and migration assays with antisense oligonucleotides in Ca9-22 and
SAS cell lines. TUG1 target genes were identified via microarray analysis. The TUG1 expression level
was considerably higher in tumor than in normal tissues, and the same result was observed in human
oral keratinocytes and all HNSCC cell lines. TUG1 knockdown dramatically inhibited cell proliferation
and migration. Furthermore, we identified nemo-like kinase, which may change in tandem with TUG1
expression. Our findings indicate the possibility for targeting the TUG1-nemo-like kinase axis as a novel
approach for the treatment of HNSCC.
Utility of long-term systolic blood pressure variability for predicting the development of type 2 diabetes mellitus
Zean Song, Yuanying Li, Young-Jae Hong, Chifa Chiang,
Masaaki Matsunaga, Yupeng He, Atsuhiko Ota, Koji Tamakoshi
and Hiroshi Yatsuya
pg(s) 220 - 236
Better identification of individuals at high risk for type 2 diabetes mellitus (T2DM) requires risk-prediction
models incorporating novel predictors. Accordingly, this study aimed to evaluate the merits of
including long-term systolic blood pressure variability (SBPV) in predicting T2DM incidence in a Japanese
cohort of 3017 participants (2446 men, 571 women; age, 36–65 years) in 2007, who were followed up
until March 2019. Consecutive SBP values, recorded between 2003 and 2007, were regressed annually
for each participant. The slope and root-mean-square error of the regression line were calculated for each
individual to represent SBPV. The significance of SBPV was examined by adding it to a multivariate Cox
model incorporating age, sex, smoking status, regular exercise, family history of diabetes, body mass index,
blood levels of triglycerides, high-density lipoprotein cholesterol, and fasting blood glucose. The c-index, net
reclassification improvement (NRI), and integrated discrimination improvement (IDI) were used to compare
the performance of the prediction models without (Model 1) and with (Model 2) SBPV. During the 9.8-year
follow-up period, 135 participants developed T2DM. Although a statistically significant difference in
c-index between Model 1 (0.785) and Model 2 (0.786) was not found, the NRI (8.312% [p < 0.001]) and
IDI (0.700% [p = 0.012]) demonstrated that the performance of Model 2 improved compared with Model
1. In conclusion, results suggested that long-term SBPV slightly improved predictive utility for T2DM
when added to a conventional prediction model. The study was registered at University Hospital Medical
Information Network Clinical Trial registry (UMIN000052544, https://www.umin.ac.jp/).
Reproducibility and validity of a food frequency questionnaire for nutrient intakes in the study areas of large-scale cohort studies in Japan
Chiho Goto, Nahomi Imaeda, Kenji Wakai, Tae Sasakabe,
Nobuaki Michihata, Isao Oze, Akihiro Hosono, Mako Nagayoshi,
Naoko Miyagawa, Etsuko Ozaki, Hiroaki Ikezaki, Hinako Nanri,
Rie Ibusuki, Sakurako Katsuura-Kamano, Kiyonori Kuriki,
Yuri Yaguchi, Ayako Kurihara and Keitaro Matsuo
pg(s) 237 - 253
The Japan Multi-Institutional Collaborative Cohort Study, the Yamagata Molecular Epidemiological
Cohort Study, and the Tsuruoka Metabolomics Cohort Study use a 47-item food frequency questionnaire
(FFQ) developed in central Japan in 2004. We applied regression analyses to estimate nutrient intakes in
the FFQ. The regression equations, however, may not be so robust and may vary among areas, even in
Japan. We aimed to evaluate the reproducibility and validity of the FFQ over an expanded area of Japan.
Healthy volunteers aged 34–70 years from 13 areas of Japan provided 12-day weighed dietary records
(WDRs) and completed two FFQs over 1 year. We evaluated reproducibility and validity by comparing
the intakes of 27 nutrients between the two FFQs and the first FFQ (FFQ1) and WDRs, respectively.
Spearman’s rank correlation coefficients (SRs) between estimates from the FFQs and WDRs were calculated
and corrected for intra-individual variation in the WDRs. Intakes of the selected nutrients estimated from
the two FFQs were equivalent. The median energy-adjusted SRs between FFQ1 and the second FFQ were
0.66 for both men and women. Regarding validity adjusted for within-individual variation, energy-adjusted
SRs for WDRs vs FFQ1 ranged from 0.13 (thiamin) to 0.79 (alcohol) for men, and the median was 0.35.
The energy-adjusted SRs ranged from 0.20 (protein) to 0.71 (alcohol) for women, and the median was 0.43.
The FFQ demonstrated high reproducibility and moderate validity, which suggests that it is appropriate to
clarify associations between diet and health and/or disease among adults in Japan.
Durvalumab-combined chemotherapy for biliary tract cancer in a Japanese expert center: initial 50 cases in daily practice
Yoshikuni Inokawa, Shunsuke Onoe, Shoji Kawakatsu,
Masamichi Hayashi, Nobuyuki Watanabe, Osamu Maeda,
Takashi Mizuno, Hideki Takami, Hiroki Kawashima, Yuichi Ando
and Tomoki Ebata
pg(s) 254 - 263
Combination regimen consisting of gemcitabine, cisplatin, and durvalumab (GCD) has been employed for
unresectable biliary tract cancer (BTC) since the end of 2022 in Japan. Here, we summarize our experience
with GCD to demonstrate the clinical outcomes in a practical setting. Patients who underwent GCD for
unresectable/recurrent BTC between January and December 2023 were investigated retrospectively. Data
for maximal response rate (RR), disease control rate (DCR), and adverse events (AEs) were collected.
Progression-free survival (PFS) and overall survival (OS) curves were generated using the Kaplan-Meyer
method. Fifty (initially unresectable, n = 32; recurrence after surgery, n = 18) consecutive patients were
enrolled, 19 of whom started GCD as second-line therapy or later. Overall RR was 24.0% including
complete response in 1 (2%) patient and partial response in 11 (22%) patients; DCR was 68.0%. The
median PFS and OS were 7.1 months and not reached, respectively. During a median follow-up period of
8.5 months, 8 (16%) patients underwent surgical resection. A total of 36 (72%) patients suffered Grade
3–5 AE, and 3 immune-related AE were controlled with injection of corticosteroid or observation. The
efficacy of GCD for unresectable/recurrent BTC was confirmed in the practical setting, with acceptable
toxicity, prolonged survival, and potential probability of resection.
Deep-learning reconstruction of the prostate improves image quality and acquisition time in T2-weighted imaging
Daichi Kobayashi, Hayato Tomita, Tsuyoshi Morimoto, Yuki Deguchi,
Hirofumi Fukuchi, Hikaru Ishida, Kumie Miyakawa,
Yasuyuki Kobayashi and Hidefumi Mimura
pg(s) 264 - 271
We compared the qualitative and quantitative quality of prostate conventional T2-weighted imaging and
T2-weighted imaging with deep-learning reconstruction. Patients with suspected prostate cancer undergoing
magnetic resonance imaging between April 2022 and June 2023 were included. Quantitative analysis was
performed to determine the signal-to-noise and contrast ratios of the perirectal fat tissue, internal obturator
muscle, and pubic tubercle. Eight periprostatic anatomical structures, overall image quality, and motion
artifacts were evaluated by two radiologists using 5- or 4-point scales. Qualitative analysis results were
compared to determine the agreement between the two radiologists. In total, 106 patients (mean age: 71 ±
8.3 years; 106 men) were included in this study. The acquisition time for conventional T2-weighted imaging
and T2-weighted imaging with deep-learning reconstruction was 4 min and 16 s and 2 min and 12 s,
respectively. The signal-to-noise ratio of the perirectal fat tissue and internal obturator muscle and contrast
ratio of fat/muscle and bone/muscle determined via T2-weighted imaging with deep-learning reconstruction
were significantly superior to those determined via conventional T2-weighted imaging (both p < 0.01).
Compared with conventional T2-weighted imaging, T2-weighted imaging with deep-learning reconstruction
showed significant improvement in the visualization of the periprostatic anatomy, overall image quality,
and motion artifacts (both p < 0.05). Compared with conventional methods, T2-weighted imaging with
deep-learning reconstruction facilitated the acquisition of good-quality magnetic resonance images of the
prostate within a shorter acquisition time. T2-weighted imaging with deep-learning reconstruction will aid
clinicians in diagnosing prostate cancer with shortened acquisition time while maintaining quantitative and
qualitative image properties.
Early introduction of intravenous oxycodone injection followed by quick titration to oral oxycodone in outpatient cancer pain treatment in opioid-naïve patients: “oxycodone bridge method”
Kazuhiro Hiramatsu, Masahide Fukaya, Taro Aoba, Atsuki Arimoto,
Hiromasa Yamashita and Yu Nakashima
pg(s) 272 - 284
Following opioid therapy initiation in opioid-naïve outpatients, cancer-related pain does not improve
immediately, and pain relief is maintained after many days. This prospective study aimed to evaluate
the feasibility of quick opioid introduction with injectable oxycodone for outpatient cancer-related pain
and bridge to oral persistent-release tablet. Patients with Numerical Rating Scale of ≥4 for cancer-related
pain were included. Injectable oxycodone 2 mg was evaluated for efficacy and safety after 30 min of
administration; in case of lower efficacy, injectable oxycodone was administered for another 30 min. For
patients exhibiting improvement 30 and 60 min after injectable oxycodone administration, oral persistent-release
tablet 5 and 10 mg were initiated, respectively. If side effects are acceptable, oral persistent-release
tablet twice daily was prescribed. The final evaluation for its efficacy and safety was conducted at revisit.
Overall satisfaction (1–5 points, higher points are better) was evaluated. The study included 23 patients (26
symptoms). The Numerical Rating Scale was improved from 6.7 ± 1.9 to 2.5 ± 2.5 and 1.3 ± 1.3 at 30
min after injectable oxycodone and revisit, respectively. Five patients with six symptoms receiving 60 min
of injectable oxycodone had Numerical Rating Scale of 3.7 ± 1.7 and 1.7 ± 1.2 at revisit. No patient had
Grade 3 or higher side effect during injectable oxycodone and at revisit. The overall satisfaction was 4.4
± 0.8. In conclusion, early injectable oxycodone introduction for opioid-naïve outpatients can be feasible
and useful as a quick bridge to oral persistent-release tablet.
Myonectin stimulates endothelial angiogenic activity in vitro and in vivo
Tomohiro Masutomi, Noriyuki Ouchi, Shukuro Yamaguchi, Koji Ohashi,
Naoya Otaka, Zhongyue Pu, Yuuki Shimizu, Toyoaki Murohara
and Rei Shibata
pg(s) 285 - 294
Endurance exercise is known to reduce the risk of cardiovascular disease. Myonectin, a myokine,
is increased by endurance exercise and affects remote organs such as the heart. However, the role of
myonectin in the blood vessels is unknown. In this study, we investigated the role of myonectin in
angiogenesis. Human umbilical vein endothelial cells (HUVECs) were treated with recombinant myonectin
to assess tube formation, proliferation, and migration. An in vivo Matrigel plug assay was performed by
transplanting Matrigel containing myonectin into myonectin-knockout (Myo-KO) mice, and angiogenic
response was evaluated. Mouse models of hindlimb ischemia were developed by ligating and removing the
femoral arteries of wild-type (WT), Myo-KO, and myonectin-overexpressing transgenic (Myo-TG) mice,
and blood flow was evaluated over time by laser Doppler imaging. In vitro, treatment with myonectin
increased the differentiation of HUVECs into vascular-like structures. Myonectin significantly stimulated
HUVEC migration, as assessed using a modified Boyden chamber assay. Treatment with myonectin also
increased HUVEC proliferation, as assessed by the MTS assay. In the Matrigel plug assay, plugs containing
myonectin displayed a significantly higher-degree of endothelial cell infiltration than plugs containing
vehicle. Angiogenic repair of ischemic hindlimbs was impaired in Myo-KO mice compared to that in WT
mice. However, Myo-TG mice had significantly increased limb perfusion after ischemic surgery compared
to that in WT mice. This study showed that myonectin acts directly on vascular endothelial cells and
promotes angiogenesis. Treatment aimed at increasing myonectin production may be useful in the treatment
of cardiovascular diseases with vascular dysfunction.
Comparative outcomes of in-situ fixation and fixation after reduction in geriatric patients with severe valgus-impacted femoral neck fractures: a retrospective multicenter (TRON group) study
Tatsuya Nobori, Yasuhiko Takegami, Katsuhiro Tokutake,
Hiroaki Nakashima, Kenichi Mishima, Masanori Okamoto,
Nobuyuki Okui and Shiro Imagama
pg(s) 295 - 304
The objective of this study was to evaluate and compare the clinical and radiographic outcomes
between in situ fixation and fixation after reduction of severe valgus-impacted femoral neck fractures in
patients aged 65 years or older. This was a multicenter retrospective study of 561 patients who underwent
open reduction and internal fixation for femoral neck fracture. From this population, we selected patients
aged 65 years and older with severe valgus-impacted femoral neck fractures characterized by a Garden
alignment index greater than 15 degrees compared to that on the non-injury side. After exclusion criteria
were applied, the study included 92 patients who were categorized into two groups: in situ fixation group
(n = 56) and fixation after reduction group (n = 36). Our analysis covered patient demographics, surgical
details, postoperative complications, radiographic evaluations, Numeric Rating Scale for pain, and Parker’s
Mobility Score for clinical outcomes. Bone union was achieved in all patients. The incidence of avascular
necrosis was consistent between the groups. Patients in the reduction group reported lower Numeric Rating
Scale scores (mean: 0 vs 2, p = 0.003) and higher Parker’s Mobility Score scores (mean: 7 vs 6, p =
0.009) compared with the in situ group. Radiographically, the reduction group showed significantly lower
femoral neck shortening (mean: 4.75 mm vs 5.75 mm, p = 0.049) and a reduced length of cannulated
cancellous screw backout (mean: 3.4 mm vs 5.4 mm, p = 0.007) at the final follow-up. Fixation after
reduction for severe valgus-impacted femoral neck fractures in patients aged 65 and above appears to be
a safe and effective approach.
Meflin/Islr is a marker of fibroblasts that arise in fibrotic regions after spinal cord injury
Yoshinori Morita,, Yukihiro Shiraki, Akira Kato, Yasuhiro Nagatani,
Ryota Ando, Hiroaki Nakashima, Shiro Imagama
and Atsushi Enomoto
pg(s) 305 - 319
Scar formation after spinal cord injury (SCI) hampers axonal regeneration and functional recovery. Previous
studies have shown that scar formation is attributable to both gliosis and fibrosis, the latter requiring
fibroblast proliferation and extracellular matrix deposition. In this setting, there are essentially two cell
types generating new fibroblasts: pericytes and tissue-resident fibroblasts. Here, we showed that Meflin, a
glycosylphosphatidylinositol-anchored protein (a specific marker of fibroblasts across multiple organs) is
expressed by fibroblasts in the normal mouse spinal cord. An in situ hybridization analysis showed that
Meflin+ cells arose from the meninges and perivascular region of the spinal parenchyma after spinal cord
compression injury. That finding was corroborated by single-cell transcriptomic data from normal and
injured mouse spinal cords. Interestingly, Meflin+ cells are positive for the fibroblast markers collagen type
I and platelet-derived growth factor receptor (PDGFR) α but not for pericyte markers such as PDGFRβ
and chondroitin sulfate proteoglycan 4 in the normal spinal cord. Those findings are consistent with the
recent view that tissue-resident fibroblasts play a central role in many other types of fibrotic disease. A
lineage-tracing experiment using a knock-in mouse line that expressed inducible Cre recombinase under
the control of the Meflin promoter showed that Meflin+ cells yield PDGFRβ+ myofibroblasts but not glial
cells positive for glial fibrillary acidic protein. These findings suggest that the Meflin+ population contains
the cells of origin of myofibroblasts that are involved in scar formation after SCI.
A comprehensive analysis of the acromial morphology and etiological factors for rotator cuff tears in Fosbury flop tears: bursal-sided partial-thickness tears versus full-thickness tears
Yukihiro Kajita, Yohei Harada, Ryosuke Takahashi, Ryosuke Sagami
and Yusuke Iwahori
pg(s) 320 - 328
Fosbury flop tears (FFTs) are a type of rotator cuff tear characterized by the tendon flipping upon
itself and adhering medially. These tears have been observed arthroscopically as either bursal-sided partial-thickness
tears (BSPTTs) or full-thickness tears (FTTs), though the mechanism leading to FFTs in these
tear types remains unclear. This study aimed to investigate the clinical features, acromial morphology, and
treatment outcomes of FFTs, stratifying patients into BSPTT and FTT groups. We included patients with
small-to-medium-sized supraspinatus tendon tears who underwent arthroscopic rotator cuff repair (ARCR).
Those with BSPTTs were categorized as Group P, and those with FTTs as Group F. Variables such as
age, sex, diabetes mellitus status, critical shoulder angle (CSA), lateral acromial angle (LAA), sagittal
and coronal acromion morphologies, Japanese Orthopaedic Association (JOA) score, and retear rate were
evaluated. Group P consisted of 13 patients, primarily younger males with traumatic tears, while Group F
included 40 patients, with a higher proportion of females. There were no significant differences between
the groups in CSA, LAA, JOA scores, or retear rates. Both groups had a high prevalence of double-floor
type osteophytes in coronal acromial morphology. FFTs were frequently observed in both BSPTTs and
FTTs, particularly in patients with double-floor osteophytes. BSPTTs with FFTs may be more common
in younger patients with trauma. Overall, ARCR outcomes for FFTs were similar between BSPTTs and
FTTs, suggesting similar efficacy in treatment across these tear types.
Biomechanical characteristics of high- and low-frequency trunk acceleration upon gait initiation related to balance ability in community-dwelling elderly people: a cross-sectional study
Masahiro Nishimura and Yasushi Uchiyama
pg(s) 329 - 338
Although trunk acceleration during walking is widely used as a measure of stability, few studies have
focused on sensitive postural control in community-dwelling elderly people to detect components related
to balance ability during gait initiation. This study aimed to clarify the biomechanical characteristics of
movement and sensitive postural control related to balance ability, focusing on high- and low-frequency
components of trunk acceleration during gait initiation. Healthy older participants were divided into two
groups (high-performance older people [Older(H)], n = 11; age, 76.2 ± 3.3 years, and low-performance
older people [Older(L)], n = 17; age, 75.8 ± 3.2 years) based on the Timed Up and Go Test time related
to balance ability while walking at their chosen speed. Trunk acceleration data were obtained from an
accelerometer on the L3-4 level spinous process. The gait velocity was measured at the first step using
a motion capture system. The acceleration data were separated into high- and low-frequency components,
and the root mean square was calculated. The level of significance was set at 5%. For the high-frequency
component, the root mean square of acceleration in Older(L) was significantly lower than that of Older(H)
in the mediolateral direction (p = 0.019) and correlated with gait velocity (r = 0.415; p < 0.001). For the
low-frequency component, the root mean square of acceleration in Older(L) was significantly lower than
that of Older(H) in the vertical (p = 0.034) and anteroposterior direction (p = 0.039). The results suggest
that low- and high-frequency components of trunk acceleration can reveal biomechanical characteristics in
community-dwelling elderly people.
Temporal changes in transcutaneous hemoglobin levels and their influencing factors in postpartum women: a longitudinal study
Mikiko Shimizu and Shigemi Iriyama
pg(s) 339 - 350
This study aimed to clarify the temporal changes in transcutaneous hemoglobin levels up to 1 month
postpartum and the influencing factors in postpartum women using a noninvasive transcutaneous hemoglobin
measuring device. The study participants were pregnant women recruited at an outpatient clinic. We collected
information on their dietary history using a concise self-administered questionnaire and an agreement
document when they were hospitalized for delivery. Transcutaneous hemoglobin levels of the mothers were
measured using Pronto (Masimo) at 1 day, 4 days, 2 weeks, and 1 month postpartum. We included 135
mothers (mean age, 31.7 years) who delivered at full term. The mean transcutaneous hemoglobin levels
decreased slightly from day 1 (11.9 ± 1.6 g/dL) to day 4 postpartum (11.8 ± 1.7 g/dL), followed by a
significant increase from day 4 to 2 weeks postpartum (13.8 ± 1.0 g/dL; p < 0.01), and no change from
2 weeks to 1 month postpartum (13.8 ± 0.9 g/dL). Iron intake in the third trimester of pregnancy affected
transcutaneous hemoglobin levels from day 4 postpartum to recovery by 2 weeks postpartum. The rapid
increase in hemoglobin levels from day 4 to 2 weeks postpartum was a novel finding. Evaluation of
hemoglobin levels in women at 2 weeks postpartum is important for postpartum recovery. Furthermore,
health guidance regarding iron intake in the third trimester of pregnancy has been suggested to be effective
in restoring postpartum hemoglobin levels.
CASE REPORTS
Environmental intervention for two cases of non-tuberculous mycobacterial disease
Yuka Kodama, Chiyako Oshikata, Kosuke Terada, Yuga Yamashita,
Ryo Nakadegawa, Hinako Masumitsu, Yuto Motobayashi, Reeko Osada,
Hirokazu Takayasu, Nami Masumoto, Takeshi Kaneko
and Naomi Tsurikisawa
pg(s) 351 - 359
Non-tuberculous Mycobacterium avium complex (MAC) disease is caused by inhalation of water or
soil dust containing MAC bacteria. Treatment of MAC disease should include not only drug treatment,
usually a three-drug regimen consisting of a macrolide, ethambutol, and a rifamycin, but also environmental
intervention. However, there is no standardized approach to environmental evaluation or remediation of
potentially harmful exposures from potting soils in home or workplace environments for patients with
non-tuberculous mycobacterial infection. We present two patients with MAC disease who were positive for
anti-MAC antibodies but had no culturable mycobacteria in sputum. One patient discontinued gardening,
and the other patient moved her many indoor plants outside. Both patients subsequently had decreased
sputum, and subsequent chest computed tomography showed decreased ground-glass opacities, consolidation,
and small nodules. Environmental intervention may therefore be sufficient treatment for mild MAC disease.
High-dose-rate surface mold with tumor translucency brachytherapy for a 103-year-old patient with skin cancer, dementia, tremor, and kyphosis: a case report
Masataka Nakai, Ken Yoshida, Tadayuki Kotsuma, Yuji Takaoka,
Hironori Akiyama, Kentaro Ozawa and Eiichi Tanaka
pg(s) 360 - 367
Cancer treatment for centenarians can be challenging. High-dose-rate surface mold brachytherapy is
a non-invasive, radical treatment modality for surface cancer. Further, it is used for patients who cannot
remain at rest or have poor posture. We performed this treatment on a 103-year-old female patient with
forehead skin cancer, dementia, tremors, and kyphosis since radical surgery and external beam radiotherapy
were not feasible. A custom-made surface mold with tube applicators was developed with vinyl sheet and
silicone. The vinyl sheet was utilized to enable tumor visualization through the mold and to confirm the
tumor position relative to the mold. The mold with tumor translucency was fixed to the tumor surface, and
the radioisotope (Ir-193) was sent remotely through tube applicators for irradiation. The planning-aim doses
were 48 Gy in eight fractions. The positional relationship between the mold and the tumor was confirmed
similarly during irradiation by checking them through the vinyl sheet before and after irradiation. We treated
the patient, although she was in constant motion during irradiation. The local tumor was well-controlled
without any metastatic disease evidence. The tumor disappeared before her eventual death 11 months
post-treatment. No serious adverse events were reported during the follow-up period. Our results indicate
that high-dose-rate surface mold with tumor translucency brachytherapy is an effective cancer treatment
for centenarians with dementia, tremors, and kyphosis.
Importance of anesthesiologists’ non-technical skills in the management of a case of life-threatening cardiac tamponade during robot-assisted thoracic surgery
Kochi Yamane and Toyofumi Fengshi Chen-Yoshikawa
pg(s) 368 - 373
Deficiency of non-technical skills may increase the number of adverse events in the operating room.
Sustained life-threatening hypotension due to intraoperative cardiac tamponade during robot-assisted
thoracic surgery is rare, requiring prompt assessment and swift decision-making. A 54-year-old woman was
scheduled to undergo robot-assisted thoracic surgery for an anterior mediastinal tumor. During the operation,
hemodynamic instability occurred despite the administration of a high dose of vasopressor. Anesthesiologists
and thoracic surgeons shared information regarding the situation, and decided to perform echocardiography
and call other physicians for assistance. Cardiac tamponade was diagnosed during echocardiography, and an
incision was made in the pericardium. The patient recovered from the critical situation and was extubated
in the operating room. Particularly in robot-assisted surgery, non-technical skills are indispensable to enable
the anesthesiologist to successfully manage critical hemodynamic instability owing to unexplained causes.
A case of innominate artery aneurysm in a pregnant woman treated by endovascular stent grafting
Noriko Yura, Hiromasa Kira, Yoshitsugu Chigusa, Masahide Kawatou,
Nozomi Kubo, Maya Komatsu, Masahito Takakura, Haruta Mogami,
Kenji Minatoya and Masaki Mandai
pg(s) 374 - 379
Innominate artery aneurysms are rare, accounting for only 0.26% of all aneurysms. Although usually
asymptomatic, they carry a significant risk of rupture, which can be fatal, making timely diagnosis and
treatment essential. There is limited literature on the management of innominate artery aneurysms during
pregnancy, and no established treatment guidelines exist. In this case, a 42-year-old multigravida woman
was diagnosed with an innominate artery aneurysm four years prior to pregnancy. Genetic panel testing
ruled out inherited connective tissue disorders, including Marfan syndrome. The aneurysm measured 24 × 36
mm and possessed a saccular configuration. At 23 weeks of gestation, due to the high risk of rupture, the
patient underwent successful endovascular stent grafting without complications. Later, the patient developed
preeclampsia and fetal growth restriction, necessitating an emergency cesarean section at 33 weeks. A
female infant was delivered, and both mother and neonate were discharged without further complications.
Open surgical intervention with cardiopulmonary bypass is the standard therapeutic approach for innominate
artery aneurysms. However, maternal and fetal mortality rates associated with cardiopulmonary bypass
during pregnancy are high. This case suggests that although innominate artery aneurysms during pregnancy
are exceedingly rare, endovascular repair with stent grafting may be a viable treatment option to avoid the
serious maternal and fetal risks associated with aneurysm rupture or open surgical repair.