1.Prognosis of biopsy-confirmed metabolic dysfunction- associated steatotic liver disease: A sub-analysis of the CLIONE study
Michihiro IWAKI ; Hideki FUJII ; Hideki HAYASHI ; Hidenori TOYODA ; Satoshi OEDA ; Hideyuki HYOGO ; Miwa KAWANAKA ; Asahiro MORISHITA ; Kensuke MUNEKAGE ; Kazuhito KAWATA ; Tsubasa TSUTSUMI ; Koji SAWADA ; Tatsuji MAESHIRO ; Hiroshi TOBITA ; Yuichi YOSHIDA ; Masafumi NAITO ; Asuka ARAKI ; Shingo ARAKAKI ; Takumi KAWAGUCHI ; Hidenao NORITAKE ; Masafumi ONO ; Tsutomu MASAKI ; Satoshi YASUDA ; Eiichi TOMITA ; Masato YONEDA ; Akihiro TOKUSHIGE ; Yoshihiro KAMADA ; Hirokazu TAKAHASHI ; Shinichiro UEDA ; Shinichi AISHIMA ; Yoshio SUMIDA ; Atsushi NAKAJIMA ; Takeshi OKANOUE ;
Clinical and Molecular Hepatology 2024;30(2):225-234
Background/Aims:
Metabolic dysfunction-associated steatotic liver disease (MASLD) was recently proposed as an alternative disease concept to nonalcoholic fatty liver disease (NAFLD). We aimed to investigate the prognosis of patients with biopsy-confirmed MASLD using data from a multicenter study.
Methods:
This was a sub-analysis of the Clinical Outcome Nonalcoholic Fatty Liver Disease (CLIONE) study that included 1,398 patients with NAFLD. Liver biopsy specimens were pathologically diagnosed and histologically scored using the NASH Clinical Research Network system, the FLIP algorithm, and the SAF score. Patients who met at least one cardiometabolic criterion were diagnosed with MASLD.
Results:
Approximately 99% of cases (n=1,381) were classified as MASLD. Patients with no cardiometabolic risk (n=17) had a significantly lower BMI than patients with MASLD (20.9 kg/m2 vs. 28.0 kg/m2, P<0.001), in addition to significantly lower levels of inflammation, ballooning, NAFLD activity score, and fibrosis stage based on liver histology. These 17 patients had a median follow-up of 5.9 years, equivalent to 115 person-years, with no deaths, liver-related events, cardiovascular events, or extrahepatic cancers. The results showed that the prognosis for pure MASLD was similar to that for the original CLIONE cohort, with 47 deaths and one patient who underwent orthotopic liver transplantation. The leading cause of death was extrahepatic cancer (n=10), while the leading causes of liver-related death were liver failure (n=9), hepatocellular carcinoma (n=8), and cholangiocarcinoma (n=4).
Conclusions
Approximately 99% of NAFLD cases were considered MASLD based on the 2023 liver disease nomenclature. The NAFLD-only group, which is not encompassed by MASLD, had a relatively mild histopathologic severity and a favorable prognosis. Consequently, the prognosis of MASLD is similar to that previously reported for NAFLD.
2.Treatment options for solitary hepatocellular carcinoma ≤5 cm: surgery vs. ablation: a multicenter retrospective study
Kazuya KARIYAMA ; Kazuhiro NOUSO ; Atsushi HIRAOKA ; Hidenori TOYODA ; Toshifumi TADA ; Kunihiko TSUJI ; Toru ISHIKAWA ; Takeshi HATANAKA ; Ei ITOBAYASHI ; Koichi TAKAGUCHI ; Akemi TSUTSUI ; Atsushi NAGANUMA ; Satoshi YASUDA ; Satoru KAKIZAKI ; Akiko WAKUTA ; Shohei SHIOTA ; Masatoshi KUDO ; Takashi KUMADA
Journal of Liver Cancer 2024;24(1):71-80
Background:
/Aim: The aim of this study was to compare the therapeutic efficacy of ablation and surgery in solitary hepatocellular carcinoma (HCC) measuring ≤5 cm with a large HCC cohort database.
Methods:
The study included consecutive 2,067 patients with solitary HCC who were treated with either ablation (n=1,248) or surgery (n=819). Th e patients were divided into three groups based on the tumor size and compared the outcomes of the two therapies using propensity score matching.
Results:
No significant difference in recurrence-free survival (RFS) or overall survival (OS) was found between surgery and ablation groups for tumors measuring ≤2 cm or >2 cm but ≤3 cm. For tumors measuring >3 cm but ≤5 cm, RFS was significantly better with surgery than with ablation (3.6 and 2.0 years, respectively, P=0.0297). However, no significant difference in OS was found between surgery and ablation in this group (6.7 and 6.0 years, respectively, P=0.668).
Conclusion
The study suggests that surgery and ablation can be equally used as a treatment for solitary HCC no more than 3 cm in diameter. For HCCs measuring 3-5 cm, the OS was not different between therapies; thus, ablation and less invasive therapy can be considered a treatment option; however, special caution should be taken to prevent recurrence.
3.Impact of adaptive radiotherapy on survival in locally advanced nasopharyngeal carcinoma treated with concurrent chemoradiotherapy
Yusuke UCHINAMI ; Koichi YASUDA ; Hideki MINATOGAWA ; Yasuhiro DEKURA ; Noboru NISHIKAWA ; Rumiko KINOSHITA ; Kentaro NISHIOKA ; Norio KATOH ; Takashi MORI ; Manami OTSUKA ; Naoki MIYAMOTO ; Ryusuke SUZUKI ; Keiji KOBASHI ; Yasushi SHIMIZU ; Jun TAGUCHI ; Nayuta TSUSHIMA ; Satoshi KANO ; Akihiro HOMMA ; Hidefumi AOYAMA
Radiation Oncology Journal 2024;42(1):74-82
Purpose:
To investigate the clinical significance of adaptive radiotherapy (ART) in locally advanced nasopharyngeal carcinoma treated with intensity-modulated radiotherapy (IMRT).
Materials and Methods:
Eligible patients were treated with concurrent chemoradiotherapy using IMRT. Planning computed tomography in ART was performed during radiotherapy, and replanning was performed. Since ART was started in May 2011 (ART group), patients who were treated without ART up to April 2011 (non-ART group) were used as the historical control. The Kaplan-Meier method was used to calculate overall survival (OS), locoregional recurrence-free survival (LRFS), progression-free survival (PFS), and distant metastasis-free survival (DMFS). LRFS for the primary tumor (LRFS_P) and regional lymph node (LRFS_LN) were also studied for more detailed analysis. Statistical significance was evaluated using the log-rank test for survival.
Results:
The ART group tended to have higher radiation doses. The median follow-up period was 127 months (range, 10 to 211 months) in the non-ART group and 61.5 months (range, 5 to 129 months) in the ART group. Compared to the non-ART group, the ART group showed significantly higher 5-year PFS (53.8% vs. 81.3%, p = 0.015) and LRFS (61.2% vs. 85.3%, p = 0.024), but not OS (80.7% vs. 80.8%, p = 0.941) and DMFS (84.6% vs. 92.7%, p = 0.255). Five-year LRFS_P was higher in the ART group (61.3% vs. 90.6%, p = 0.005), but LRFS_LN did not show a significant difference (91.9% vs. 96.2%, p = 0.541).
Conclusion
Although there were differences in the patient backgrounds between the two groups, this study suggests the potential effectiveness of ART in improving locoregional control, especially in the primary tumor.
4.Association Between the Cool Temperature-dependent Suppression of Colonic Peristalsis and Transient Receptor Potential Melastatin 8 Activation in Both a Randomized Clinical Trial and an Animal Model
Satoshi SUGINO ; Ken INOUE ; Reo KOBAYASHI ; Ryohei HIROSE ; Toshifumi DOI ; Akihito HARUSATO ; Osamu DOHI ; Naohisa YOSHIDA ; Kazuhiko UCHIYAMA ; Takeshi ISHIKAWA ; Tomohisa TAKAGI ; Hiroaki YASUDA ; Hideyuki KONISHI ; Yasuko HIRAI ; Katsura MIZUSHIMA ; Yuji NAITO ; Toshifumi TSUJI ; Takashi OKUDA ; Keizo KAGAWA ; Makoto TOMINAGA ; Yoshito ITOH
Journal of Neurogastroenterology and Motility 2022;28(4):693-705
Background/Aims:
Several studies have assessed the effect of cool temperature on colonic peristalsis. Transient receptor potential melastatin 8 (TRPM8) is a temperature-sensitive ion channel activated by mild cooling expressed in the colon. We examined the antispasmodic effect of cool temperature on colonic peristalsis in a prospective, randomized, single-blind trial and based on the video imaging and intraluminal pressure of the proximal colon in rats and TRPM8-deficient mice.
Methods:
In the clinical trial, we randomly assigned a total of 94 patients scheduled to undergo colonoscopy to 2 groups: the mildly cool water (n = 47) and control (n = 47) groups. We used 20 mL of 15°C water for the mildly cool water. The primary outcome was the proportion of subjects with improved peristalsis after treatment. In the rodent proximal colon, we evaluated the intraluminal pressure and performed video imaging of the rodent proximal colon with cool water administration into the colonic lumen. Clinical trial registry website (Trial No. UMIN-CTR; UMIN000030725).
Results:
In the randomized controlled trial, after treatment, the proportion of subjects with no peristalsis with cool water was significantly higher than that in the placebo group (44.7% vs 23.4%; P < 0.05). In the rodent colon model, cool temperature water was associated with a significant decrease in colonic peristalsis through its suppression of the ratio of peak frequency (P < 0.05). Cool temperaturetreated TRPM8-deficient mice did not show a reduction in colonic peristalsis compared with wild-type mice.
Conclusion
For the first time, this study demonstrates that cool temperature-dependent suppression of colonic peristalsis may be associated with TRPM8 activation.
5.The Efficacy of Choreitogoshimotsuto for Radiation Hemorrhagic Cystitis
Satoshi TAMADA ; Minoru KATO ; Takeshi YAMASAKI ; Sayaka YASUDA ; Taro IGUCHI
Kampo Medicine 2022;73(2):187-189
We investigated the efficacy of choreitogoshimotsuto for radiation hemorrhagic cystitis. Of the 11 patients who could be followed up, hematuria disappeared in 8 cases. The median time to disappearance of gross hematuria was 74 days. There was no recurrence. Of the 3 ineffective patients, one had urinary diversion, and two had transurethral electrocoagulation and hyperbaric oxygen therapy. There were no adverse events associated with the use of choreitogoshimotsuto. Choreitogoshimotsuto might be effective for radiation hemorrhagic cystitis.
6.Behavior Modification from Shower Bathing to Bathtub Bathing Affects Sleep and Mental Health: Plain Bathing and Bathing with an Artificial Bath Additive Containing Inorganic Salts and Carbon Dioxide
Takaaki KUBO ; Tomonori YASUDA ; Satoshi WATANABE ; Taichi ISHIZAWA ; Mitsuo TSUNAKAWA ; Shingo YANO ; Jun-ichi IIYAMA
The Journal of The Japanese Society of Balneology, Climatology and Physical Medicine 2017;80(3):124-134
Frequent bathtub bathing (BB) improves sleep quality and mental health of middle-aged and older Japanese individuals. This study investigated the chronic effects of BB with and without a bath additive (bathtub bathing with KIKIYU [BBK]) in healthy young adults. The study involved healthy young adults who habitually showered, as opposed to bathing. Nineteen participants were randomly assigned to either the BB or BBK groups for 14 consecutive nights. After a 2-week washout period (shower bathing), the participants were asked to switch their bathing styles (a crossover design). The artificial bath additive for the BBK group contained inorganic salts and carbon dioxide. The participants were evaluated by using the Oguri-Shirakawa-Azumi Sleep Inventory-Middle-aged version (OSA-MA) and 1-ch sleep electroencephalography (EEG) for sleep quality, the Profile of Mood States (POMS), Self-rating Depression Scale (SDS), and Apathy Scale (AS) for mental conditions. Sleepiness on waking and refreshing scores in the OSA-MA significantly differed between the shower bathing and BBK groups. EEG results did not significantly differ among the bathing styles. Vigor T-score and total mood disturbance (TMD) scores showed significant differences in the two bathing groups (shower vs. bathing), and fatigue T-score was significantly lower in the BBK group compared with both the BB and shower groups. SDS score was significantly lower in the BBK group compared with the shower group. AS score was significantly lower in the two bathing groups (shower vs. bathing). The OSA-MA score was possibly influenced by vasodilatation and circulation by using carbon dioxide and keeping the body warm after bathing by using inorganic salts. The OSA-MA score was possible also affected by fatigue alleviation and maintenance of vitality by using a citrus lemon scent and yellow-green hue. Furthermore, frequent body heating affects the central nervous function related to mood and emotion. Based on these results, we can conclude that BB and BBK prior to shower bathing improved the mental health of the young adults in this study.
7.Behavior Change from the Shower Bathing to Bath Bathing Affects Sleep and Working Efficiency
Tomonori YASUDA ; Takaaki KUBO ; Yoshihisa MASUMITSU ; Yoshihiro IWASHITA ; Satoshi WATANABE ; Taichi ISHIZAWA ; Mitsuo TSUNAKAWA ; Shingo YANO ; Jun-ichi IIYAMA
The Journal of The Japanese Society of Balneology, Climatology and Physical Medicine 2015;78(4):341-352
Objective: The purpose of this study was to examine the effects of bathtub bathing (BB) on sleep and working efficiency of healthy young adult students. Furthermore, the effects of BB and prolonged increased body temperature from the use of insulating sheets and sleeping bags after BB (warming after BB: BBW) on sleep and working efficiency were investigated. Subjects: Eighteen (six males, 12 females) healthy young students (19.6±0.7 years old, mean±SD) who habitually took showers instead of baths participated in this study. Informed consent was obtained from all of the subjects, and the study was approved by the Ethics Committee of Kumamoto Health Science University. Methods: Subjects were randomly assigned to two groups (n=9 in each group). The subjects in the BB group were immersed in their home bathtub to the supraclavicular level and instructed to rest for 10 min with the temperature regulated at 41°C. The subjects in the BBW group followed the same bathing protocol, and they then rested in a sleeping bag and sheet for 30 min in order to keep their bodies warm. The length of each study period was 2 weeks in a crossover design. After the 2-week-long washout periods, the subject groups were switched. The subjects were evaluated with the Oguri-Shirakawa-Azumi sleep inventory, MA version (OSA-MA), which utilizes a visual analog scale (VAS) with which subjects rate their sleep when they wake up, and Purdue Pegboard Assembly test. These tests were employed before and after the BB and BBW sessions, resulting in four testing periods in the 6-week period. Results: Sleep rating on the OSA-MA was no significant difference in both the BB and BBW groups compared to ratings recorded after showering. The subjects in the BB and BBW groups had significantly increased VAS ratings for “Feeling of sound sleep,” “Refreshing,” and “Lightness of the body” compared to the ratings after showering. The mean Purdue Pegboard test scores of the subjects in both the BB and BBW groups were significantly higher than those recorded after showering. Discussion: Changing bathing style from shower to BB or BBW improved the working efficiency of students on the Purdue pegboard test. BB and BBW resulted in soothing effects owing to improvements in the subjects’ quality of sleep.
8.12-1 The chronic effects of bathtub bathing, whole body warming, and herbal extracts on the mental conditions of healthy young persons
Takaaki KUBO ; Tomonori YASUDA ; Yoshihisa MASUMITSU ; Yoshihiro IWASHITA ; Satoshi WATANABE ; Taichi ISHIZAWA ; Mitsuo TSUNAKAWA ; Shingo YANO ; Jun-ichi IIYAMA
The Journal of The Japanese Society of Balneology, Climatology and Physical Medicine 2014;77(5):511-512
Objective: The purpose of this study was to clarify the chronic effects of bathtub bathing (BB), whole body warming after bathtub bathing (BBW), and bathtub bathing with herbal extracts (BBH) on the mental condition of healthy young persons. Subjects and Methods: Experiment 1: Eighteen (6 male and 12 female; age: 19.6±0.7 years, mean ± SD) healthy young persons who were taking a shower habitually but not bathtub bathing participated in this study. From November 2012 to December 2012, subjects were randomly assigned into two groups (each 3 male, 6 female): those who had BB or 30-min BBW 14 times for 14 consecutive nights during a 2-week period. After a 2-week washout period, subjects were asked to switch their bathing conditions (a cross-over design). Experiment 2: Twenty (8 male and 12 female; age: 21.3±1.6 years, mean ± SD) healthy young persons who were taking a shower habitually but not bathtub bathing participated in this study. From October 2013 to November 2013, subejects (4male and 6 female) were randomly assigned to undergo BB or BBH. The herbal extract contained Dong dang gui (Japanese Angelica Root), Chimpi (Citrus Unshiu peel), Chamomilla recutita, and ginger extracts. After a 2-week washout period, subjects were asked switch to the other bathing condition (a cross-over design). All participants provided informed consent for participation in these studies, and these studies were approved by the Ethics Committee of the Kumamoto Health Science University. The subjects immersed their bodies up to the supraclavian for 10 min, in tap water adjusted to a temperature of 41 °C in their bathtub at home. The subjects’ mental conditions were assessed using Profile of Mood States short version questionnaire. The differences in the effect of BB and BBW, as well as those of BB and BBH on the subjects’ mental conditions and their mental conditions pre-BB and post-BB, pre-BBW and post-BBW, pre-BBH and post-BBH were analyzed using Wilcoxon’s signed-rank sum test. Results: The points for depression-dejection, fatigue, and confusion in those who had BBH significantly converged to the median average (50 points) compared to the points in those who had BB. The points for anger-hostility before BBW and BBH significantly converged to the median average (50 points) after BBW and BBH, and there were no significant differences in points before and after BB. Conclusions: The subjects’ anger-hostility was influenced by body warming in BBW and the vasodilatory components of the herbal extracts. The subjects’ depression-dejection and fatigue was influenced by the fragrance and color of herbal extracts.
9.12-3 Effect of bathtub bathing on students’ working efficiency
Tomonori YASUDA ; Yoshihisa MASUMITSU ; Takaaki KUBO ; Yoshihiro IWASHITA ; Satoshi WATANABE ; Taichi ISHIZAWA ; Mitsuo TSUNAKAWA ; Shingo YANO ; Jun-ichi IIYAMA
The Journal of The Japanese Society of Balneology, Climatology and Physical Medicine 2014;77(5):514-514
Introduction: Some students take showers instead of baths for economic reasons or because they dislike cleaning the bathtub. The purpose of this study was to examine the effect of bathing routines on students’ working efficiency. Subjects: Seventeen (six male and 11 female) healthy young students (19.6 ± 0.7 years old, mean ± SD) who habitually took showers instead of baths participated in this study. Informed consent was obtained from all the subjects and the study was approved by the Ethics Committee of Kumamoto Health Science University. Method: Subjects were randomly assigned into two groups. The subjects in the first group (bathtub bathing [BB]) were immersed to the supraclavicular level in their home bathtub and instructed to rest for 10 minutes with the temperature regulated at 41°C. The subjects of the second group (whole-body warming after BB [BBW]) followed the same bathing protocol and then rested in a sleeping bag and sheet for 30 minutes to keep their bodies warm. Each period was carried out over 2 weeks in a cross-over design. Washout periods were 2 weeks long. The evaluation items of this study included the obstructive sleep apnea (OSA) sleep inventory MA version (OSA-MA), a questionnaire containing a visual analog scale (VAS) to judge the subjective bathing effect, profile of mood states, salivary stress marker (α-amylase), and the Purdue Pegboard test. These tests were evaluated before and after the BB sessions, BBW sessions, and washout interval for a total of four times in a 6-week period. Result: Participants tended to report a better sleep feeling on the OSA-MA after the BB or BBW sessions than after showering. There were significantly better changes in both the BB and BBW in the VAS for bathing effect in terms of “Sense of deep sleep,” “Body fatigue,” “Light feeling of the body” than after a shower. The mean α-amylase value in the saliva of the BBW group participants was significantly lower than that after showering. The mean Purdue Pegboard test scores of both the BB and BBW sessions were significantly higher than that after the shower. Discussion: Sleep quality seemed to be more improved after BB or BBW than after showering, perhaps due to reduced stress. Work efficiency also increased in the BB and BBW groups.
10.Histopathological Case of Uterine Carcinoid Tumor Metastasized to the Lung.
Satoshi TOSHIMA ; Yo YASUDA ; Tadashi ARAI ; Yuji ITO ; Kazuyoshi HAYAKAWA ; Tadatake TAKAYA ; Momoe DOI ; Chiken SHIBUYA ; Toshiya ITO ; Yoshitomo KASHIKI ; Naoki YOSHIMI
Journal of the Japanese Association of Rural Medicine 1999;48(1):48-53
With the diagnosis of metastatic tumor of the lung suspected, we had a chance to experience a histopathological case of carcinoma of the uterine cervix (adenoid squamous cell carcinoma), which was thought to coexist with carcinoid tumor. In this paper, we report the results of cytological as well as histological examinations of the case.
The patient was as 43-year-old woman. She visited our hospital, complaining about abnormally prolonged uterine bleeding (metrorrhagia). Cytodiagnosis was performed with a Papanicolaou smear. A microscopic examination revealed squamous cell carcinoma occurring together with adenocarcinoma. A similar finding was obtained by cervical biopsy. Thus, the case was diagnosed as adenoid squamous cell carcinoma.
Then the patient underwent radical hysterectomy and lymphadenectomy, followed by chemotherapy. After leaving the hospital, she was put under doctor-monitored observation. About 4 years after the surgery, a chest x-ray examination found abnormal shadows. For inspection, bronchoscopy was performed. Carcinoid of the lung was diagnosed through histopathological as well as electron microscopic examination of specimens taken from bronchial polyps during bronchoscopy. At the same time a cytologic study was conducted. It also revealed neoplasms strongly suspected of caricinoid tumors. Retrospective studies of cytological and histopathological images of the uterine cervix when the patient first visited us found only adenocarcinoma and squamous cell carcinoma, but no signs of carcinoid tumors. However, the immunohistological staining of NSE and chromoganins A, both neuroendocrine markers, showed positive findings in some adenocarcinomatous parts of the tissues of the unterine cervix. Therefore, we considered that the cervical cancer is compounded of adenoid squamous cell carcinomas and tumors having properties of neuroendocrine cells.
From this, we concluded that it is necessary to take into account a differential diagnosis of neuroendocrine tumors including carcinoid of the uterine cervix when less differentiated adenocarcinoma and squamous cell carcinoma are suspected in histological and cytological examinations. Furthermore, we thought it important to make a definite diagnosis after meticulous examinations by immunohistological staining and electron microscopy.


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