1.Therapeutic Effect of Reibaisan (WTMCGEP) in Patients with Advanced Cancer
Kazutomo SAWAI ; Taketoshi YAMASAKI ; Takashi MINE
Kampo Medicine 2023;74(1):42-53
		                        		
		                        			
		                        			Here we report 3 cases of advanced cancer using multidisciplinary treatment including reibaisan (WTMCGEP, a dry extract of Wisteria floribunda, Trapa natans, Myristica fragrans, Coix semen, Ganoderma lucidum, Elfvingia applanata, Punica granatum). Case 1 : 87-year-old man, suffering from stage IV esophageal squamous cell carcinoma (ESCC) with aortic and bronchial invasion, was referred to our clinic for palliative care. He had radiotherapy and chemotherapy. Only one course of chemotherapy was performed due to its intolerable side effects. The treatment with reibaisan started 11 months after the diagnosis. ESCC disappeared after 17 months of reibaisan treatment, and no relapse was observed for 66 months after the diagnosis. Case 2 : 79-year-old man, suffering from stage III ESCC, was initially scheduled for surgery after preoperative chemotherapy. Only one course of preoperative chemotherapy was performed because of its intolerable side effects. Therefore, radiotherapy combined with reibaisan followed. ESCC disappeared 6 months later, and no relapse was observed for 33 months after the diagnosis. Case 3 : 73-year-old woman, suffering from stage IV pancreatic cancer with systemic metastasis (brain, lung, and peritoneum). She initially showed Trousseau syndrome and was treated with low-molecular-weight heparin for multiple cerebral infarctions. One-month palliative chemotherapy and reibaisan resulted in a rapid reduction of ascites and improvement of neurological symptoms. Her progression-free survival period was 7 months. She lived 13 months thereafter. This suggests that reibaisan, which contains crude drugs that have been shown to have antitumor effects, may be another promising treatment for advanced cancers.
		                        		
		                        		
		                        		
		                        	
2.Cardiopulmonary arrest due to bronchoscopy-induced Takotsubo syndrome in a patient with antineutrophil cytoplasmic autoantibody-associated lung disease: a case report
Yoshio OKANO ; Takashi YAMASAKI ; Ryuichiro IMAI ; Hiroyasu OKAZAKI ; Yuji HIGUCHI ; Tsutomu SHINOHARA
Journal of Rural Medicine 2022;17(3):181-183
		                        		
		                        			
		                        			Objective: Cardiac arrest (CA) has been observed in some patients with Takotsubo syndrome (TTS), most of whom had CA at the initial presentation of TTS. The objective of this report was to discuss the factors underlying the onset of this syndrome.Case presentation: A 72-year-old woman with refractory antineutrophil cytoplasmic autoantibody-associated lung disease was referred to our hospital. Twenty minutes after bronchoscopic examination, cardiopulmonary arrest suddenly occurred. Resuscitation immediately resumed her heartbeat and spontaneous breathing. Subsequent 12-lead electrocardiography, echocardiography, and left ventricular angiography revealed TTS.Conclusion: This case indicates that bronchoscopy can cause severe TTS, especially in patients with systemic inflammation.
		                        		
		                        		
		                        		
		                        	
3.Feasibility and safety of endoscopic submucosal dissection for lesions in proximity to a colonic diverticulum
Nobuaki IKEZAWA ; Takashi TOYONAGA ; Shinwa TANAKA ; Tetsuya YOSHIZAKI ; Toshitatsu TAKAO ; Hirofumi ABE ; Hiroya SAKAGUCHI ; Kazunori TSUDA ; Satoshi URAKAMI ; Tatsuya NAKAI ; Taku HARADA ; Kou MIURA ; Takahisa YAMASAKI ; Stuart KOSTALAS ; Yoshinori MORITA ; Yuzo KODAMA
Clinical Endoscopy 2022;55(3):417-425
		                        		
		                        			 Background/Aims:
		                        			Endoscopic submucosal dissection (ESD) for diverticulum-associated colorectal lesions is generally contraindicated because of the high risk of perforation. Several studies on patients with such lesions treated with ESD have been reported recently. However, the feasibility and safety of ESD for lesions in proximity to a colonic diverticulum (D-ESD) have not been fully clarified. The aim of this study was to evaluate the feasibility and safety of D-ESD. 
		                        		
		                        			Methods:
		                        			D-ESD was defined as ESD for lesions within approximately 3 mm of a diverticulum. Twenty-six consecutive patients who underwent D-ESD were included. Two strategic approaches were used depending on whether submucosal dissection of the diverticulum-related part was required (strategy B) or not (strategy A). Treatment outcomes and adverse events associated with each strategy were analyzed. 
		                        		
		                        			Results:
		                        			The en bloc resection rate was 96.2%. The rates of R0 and curative resection in strategies A and B were 80.8%, 73.1%, 84.6%, and 70.6%, respectively. Two cases of intraoperative perforation and one case of delayed perforation occurred. The delayed perforation case required emergency surgery, but the other cases were managed conservatively. 
		                        		
		                        			Conclusions
		                        			D-ESD may be a feasible treatment option. However, it should be performed in a high-volume center by expert hands because it requires highly skilled endoscopic techniques. 
		                        		
		                        		
		                        		
		                        	
4.White Opaque Substance, a New Optical Marker on Magnifying Endoscopy: Usefulness in Diagnosing Colorectal Epithelial Neoplasms
Kazutomo YAMASAKI ; Takashi HISABE ; Kenshi YAO ; Hiroshi ISHIHARA ; Kentaro IMAMURA ; Tatsuhisa YASAKA ; Hiroshi TANABE ; Akinori IWASHITA ; Toshiharu UEKI
Clinical Endoscopy 2021;54(4):570-577
		                        		
		                        			Background/Aims:
		                        			A white substance that is opaque to endoscopic light is sometimes observed in the epithelium during narrowband imaging with magnifying endoscopy of gastric or colorectal epithelial neoplasms. This prospective observational study aimed to determine whether the morphology of the white opaque substance (WOS) allows differential diagnosis between colorectal adenoma and carcinoma. 
		                        		
		                        			Methods:
		                        			A consecutive series of patients with colorectal adenomas or early carcinomas who underwent endoscopic resection or surgical excision were studied. The morphology of the WOS was determined based on endoscopic images before the histopathological diagnosis was performed. The primary outcome was the diagnostic performance of an irregular WOS as a marker of colorectal carcinoma. 
		                        		
		                        			Results:
		                        			The study analyzed 125 lesions. A total of 33 lesions showed an irregular WOS, and 92 lesions showed a regular WOS. Among the 33 lesions found to show an irregular WOS, 30 were carcinomas. Among the 92 lesions showing a regular WOS, 79 were adenomas. With irregular WOS as a marker of carcinoma, the diagnostic accuracy was 87%, sensitivity was 91%, and specificity was 86%. 
		                        		
		                        			Conclusions
		                        			This study demonstrated the potential usefulness of the morphology of the WOS as a marker for the differential diagnosis between adenoma and carcinoma in cases of colorectal epithelial neoplasms.
		                        		
		                        		
		                        		
		                        	
5.White Opaque Substance, a New Optical Marker on Magnifying Endoscopy: Usefulness in Diagnosing Colorectal Epithelial Neoplasms
Kazutomo YAMASAKI ; Takashi HISABE ; Kenshi YAO ; Hiroshi ISHIHARA ; Kentaro IMAMURA ; Tatsuhisa YASAKA ; Hiroshi TANABE ; Akinori IWASHITA ; Toshiharu UEKI
Clinical Endoscopy 2021;54(4):570-577
		                        		
		                        			Background/Aims:
		                        			A white substance that is opaque to endoscopic light is sometimes observed in the epithelium during narrowband imaging with magnifying endoscopy of gastric or colorectal epithelial neoplasms. This prospective observational study aimed to determine whether the morphology of the white opaque substance (WOS) allows differential diagnosis between colorectal adenoma and carcinoma. 
		                        		
		                        			Methods:
		                        			A consecutive series of patients with colorectal adenomas or early carcinomas who underwent endoscopic resection or surgical excision were studied. The morphology of the WOS was determined based on endoscopic images before the histopathological diagnosis was performed. The primary outcome was the diagnostic performance of an irregular WOS as a marker of colorectal carcinoma. 
		                        		
		                        			Results:
		                        			The study analyzed 125 lesions. A total of 33 lesions showed an irregular WOS, and 92 lesions showed a regular WOS. Among the 33 lesions found to show an irregular WOS, 30 were carcinomas. Among the 92 lesions showing a regular WOS, 79 were adenomas. With irregular WOS as a marker of carcinoma, the diagnostic accuracy was 87%, sensitivity was 91%, and specificity was 86%. 
		                        		
		                        			Conclusions
		                        			This study demonstrated the potential usefulness of the morphology of the WOS as a marker for the differential diagnosis between adenoma and carcinoma in cases of colorectal epithelial neoplasms.
		                        		
		                        		
		                        		
		                        	
6.A Randomized Double-blind Placebo-controlled Trial on the Effect of Magnesium Oxide in Patients With Chronic Constipation
Sumire MORI ; Toshihiko TOMITA ; Kazuki FUJIMURA ; Haruki ASANO ; Tomohiro OGAWA ; Takahisa YAMASAKI ; Takashi KONDO ; Tomoaki KONO ; Katsuyuki TOZAWA ; Tadayuki OSHIMA ; Hirokazu FUKUI ; Takeshi KIMURA ; Jiro WATARI ; Hiroto MIWA
Journal of Neurogastroenterology and Motility 2019;25(4):563-575
		                        		
		                        			
		                        			BACKGROUND/AIMS: Magnesium oxide (MgO) has been frequently used as a treatment for chronic constipation (CC) since the 1980s in Japan. The aim of this study is to evaluate its therapeutic effects of MgO in Japanese CC patients. METHODS: We conducted a randomized, double-blind placebo-controlled study. Thirty-four female patients with mild to moderate constipation were randomly assigned to either placebo (n = 17) or MgO group (n = 17) 0.5 g × 3/day for 28 days. Primary endpoint was overall improvement over the 4-week study period. Secondary endpoints were changes from baseline in spontaneous bowel movement (SBM), response rates of complete spontaneous bowel movement (CSBM), stool form, colonic transit time (CTT), abdominal symptom, and quality of life. RESULTS: One patient failed to complete the medication regimen and was omitted from analysis: data from 16 placebo and 17 MgO patients were analyzed. The primary endpoint was met by 25.0% of placebo vs 70.6% of MgO group (P = 0.015). MgO significantly improved SBM changes compared to placebo (P = 0.002). However, MgO did not significantly improved response rates of CSBM compared to placebo (P = 0.76). In addition, MgO significantly improved Bristol stool form scale changes (P < 0.001) and significantly improved CTT compared to the placebo group (P < 0.001). MgO significantly improved the Japanese version of the patient assessment of constipation quality of life (P = 0.003). CONCLUSION: Our placebo-controlled study demonstrated that MgO was effective treatment for improving defecation status and shortened CTT in Japanese CC patients with mild to moderate symptoms.
		                        		
		                        		
		                        		
		                        			Asian Continental Ancestry Group
		                        			;
		                        		
		                        			Colon
		                        			;
		                        		
		                        			Constipation
		                        			;
		                        		
		                        			Defecation
		                        			;
		                        		
		                        			Double-Blind Method
		                        			;
		                        		
		                        			Female
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Japan
		                        			;
		                        		
		                        			Magnesium Oxide
		                        			;
		                        		
		                        			Magnesium
		                        			;
		                        		
		                        			Quality of Life
		                        			;
		                        		
		                        			Therapeutic Uses
		                        			
		                        		
		                        	
7.Intravenous Corticotropin-releasing Hormone Administration Increases Esophageal Electrical Sensitivity in Healthy Individuals.
Takahisa YAMASAKI ; Toshihiko TOMITA ; Mayu TAKIMOTO ; Takashi KONDO ; Katsuyuki TOZAWA ; Yoshio OHDA ; Tadayuki OSHIMA ; Hirokazu FUKUI ; Jiro WATARI ; Hiroto MIWA
Journal of Neurogastroenterology and Motility 2017;23(4):526-532
		                        		
		                        			
		                        			BACKGROUND/AIMS: When a person is experiencing stress, corticotropin-releasing hormone (CRH) can modulate gut physiologies, such as visceral sensation or gastrointestinal motility, and its intravenous administration mimics stress-induced physiological changes. However, the influence of CRH on the esophagus is yet unknown. Accordingly, we investigated whether intravenous CRH administration increases esophageal sensitivity to electrical stimulation in healthy Japanese subjects. METHODS: Twenty healthy subjects were recruited. We quantified the initial perception threshold (IPT) every 15 minutes after CRH injection. Venous blood was collected with a cannula, and both plasma adrenocorticotropic hormone (ACTH) and cortisol were measured at pre-stimulation, 0, 30, 60, 90, and 120 minutes. The results from each time point were compared against a baseline IPT obtained before electrical stimulation was initiated. RESULTS: When compared to the baseline IPT value (16.9 ± 4.5), CRH significantly decreased electrical threshold of the esophagus at 30, 45, 60, 75 minutes (14.1 ± 4.2, 13.1 ± 5.0, 12.1 ± 5.7, 14.0 ± 5.8 minutes, P < 0.01, respectively) after CRH injection, suggesting that CRH increased esophageal sensitivity to the electrical stimulus. CRH also significantly increased plasma ACTH levels at 30 minutes (50.3 ± 17.7, P < 0.01), and cortisol levels at 30 minutes (22.0 ± 6.7 minutes, P < 0.01) and 60 minutes (20.3 ± 6.7 minutes, P < 0.01) after CRH injection, when compared to the pre-stimulation ACTH and cortisol values. CONCLUSION: Intravenous CRH administration increased esophageal electrical sensitivity in normal subjects, emphasizing the important role of stress in esophageal sensitivity.
		                        		
		                        		
		                        		
		                        			Administration, Intravenous
		                        			;
		                        		
		                        			Adrenocorticotropic Hormone
		                        			;
		                        		
		                        			Asian Continental Ancestry Group
		                        			;
		                        		
		                        			Catheters
		                        			;
		                        		
		                        			Corticotropin-Releasing Hormone*
		                        			;
		                        		
		                        			Electric Stimulation
		                        			;
		                        		
		                        			Esophagus
		                        			;
		                        		
		                        			Gastrointestinal Motility
		                        			;
		                        		
		                        			Healthy Volunteers
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Hydrocortisone
		                        			;
		                        		
		                        			Plasma
		                        			;
		                        		
		                        			Sensation
		                        			
		                        		
		                        	
8.Prevalence of Gastric Motility Disorders in Patients with Functional Dyspepsia.
Haruki ASANO ; Toshihiko TOMITA ; Kumiko NAKAMURA ; Takahisa YAMASAKI ; Takuya OKUGAWA ; Takashi KONDO ; Tomoaki KONO ; Katsuyuki TOZAWA ; Yoshio OHDA ; Tadayuki OSHIMA ; Hirokazu FUKUI ; Kazuhito FUKUSHIMA ; Shozo HIROTA ; Jiro WATARI ; Hiroto MIWA
Journal of Neurogastroenterology and Motility 2017;23(3):392-399
		                        		
		                        			
		                        			BACKGROUND/AIMS: Gastric motility abnormalities have been considered to be pathophysiological features of functional dyspepsia (FD) that are closely related to dyspepsia symptoms, especially postprandial distress syndrome (PDS). The aims of this study are to (1) investigate the prevalence of gastric motility disorders and (2) evaluate the association between gastric motility abnormalities and dyspeptic symptoms using gastric scintigraphy in the PDS type of FD. METHODS: Forty healthy subjects and 94 PDS type FD patients were enrolled in the study. The volunteers and patients ingested a radiolabeled (technetium-99m) solid test meal, and scintigraphic images were recorded. Gastric accommodation and emptying were assessed by scintigraphic imaging. The patients’ dyspeptic symptoms were also explored using self-completed symptom questionnaires with 10 variables (4 scales, 0–3 points) at the same time. RESULTS: In 94 Japanese FD patients, the prevalence of impaired gastric accommodation and delayed emptying were 14.9% (14/94) and 10.6% (10/94), respectively. Gastric motility abnormalities were seen in 25.5% (24/94) of FD patients. There was no association between gastric motility abnormalities and dyspeptic symptoms. CONCLUSIONS: Gastric motility abnormalities were seen in 25.5% of Japanese PDS type FD patients. However, there was no association between gastric motility abnormalities and dyspeptic symptoms on gastric scintigraphy.
		                        		
		                        		
		                        		
		                        			Asian Continental Ancestry Group
		                        			;
		                        		
		                        			Dyspepsia*
		                        			;
		                        		
		                        			Healthy Volunteers
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Meals
		                        			;
		                        		
		                        			Prevalence*
		                        			;
		                        		
		                        			Radionuclide Imaging
		                        			;
		                        		
		                        			Stomach
		                        			;
		                        		
		                        			Volunteers
		                        			;
		                        		
		                        			Weights and Measures
		                        			
		                        		
		                        	
9.A Case of Refractory Transient Ischemic Attack Successfully Managed with Chotosan
Kazutomo SAWAI ; Taketoshi YAMASAKI ; Takashi MINE
Kampo Medicine 2017;68(4):345-351
		                        		
		                        			
		                        			We report a case of refractory transient ischemic attack (TIA) successfully treated with chotosan. A 64-year-old woman with recurrent right hemiparesis and dysarthria was seen in our clinic. Twenty-three months before coming to our clinic, she had a history of right hemiparesis and dysarthria, which resolved soon after treatment. Magnetic resonance imaging (MRI) revealed an ischemic legion in the left corona radiata. Then 4 months before coming, she had repeated transient right hemiparesis and dysarthria, which lasted for 40 to 50 minutes and recurred 3 to 4 times a week. She was hospitalized and treated with an intensive TIA therapy including direct thrombin inhibitor, dual antiplatelet therapy, statin, calcium channel blocker and benzodiazepine. Though she continued the therapy for 4 months, it proved ineffective. She was referred to our clinic, and we started to administer chotosan 7.5 g per day for anxiety and dizziness during an attack. Chotosan attenuated TIA within a week, but aggravated after discontinuation on her own. The medication was resumed and TIA diminished within three months. Chotosan treatment has now been continued for 17 months without a single TIA for 14 months. Multiple studies have shown the protective effect of chotosan against cerebrovascular diseases including cerebral infarction and TIA. Therefore, chotosan may be an effective prescription for refractory TIA.
		                        		
		                        		
		                        		
		                        	
10.Prevalence and Self-recognition of Chronic Constipation: Results of an Internet Survey.
Akio TAMURA ; Toshihiko TOMITA ; Tadayuki OSHIMA ; Fumihiko TOYOSHIMA ; Takahisa YAMASAKI ; Takuya OKUGAWA ; Takashi KONDO ; Tomoaki KONO ; Katsuyuki TOZAWA ; Hisatomo IKEHARA ; Yoshio OHDA ; Hirokazu FUKUI ; Jiro WATARI ; Hiroto MIWA
Journal of Neurogastroenterology and Motility 2016;22(4):677-685
		                        		
		                        			
		                        			BACKGROUND/AIMS: Although chronic constipation is a common symptom, to date no international consensus has been reached regarding its definition. The aims of this study were (1) to investigate defecation habits and (2) to examine the prevalence of constipation using the Japanese Society of Internal Medicine (JSIM) and the Rome III criteria using an online survey. METHODS: An online questionnaire composed of items on the frequency, interval, form of defecation, the management, and self-recognition of constipation (reference standard of constipation) was created. A total of 5155 valid responses were received. In addition, constipation symptoms were evaluated through a survey using the JSIM and the Rome III criteria. RESULTS: In the internet survey, 28.4% of the respondents considered themselves to be constipated. Stratified by sex, significantly more females (37.5%) than males (19.1%) considered themselves to be constipated (P < 0.001). The prevalence of constipation among the respondents was 28.0% using the Rome III, but only 10.1% using the JSIM. The diagnostic accuracy was 73.2% for the Rome III and 78.1% for the JSIM, while the diagnostic specificity was 81.1% for the Rome III and 97.5% for the JSIM. However, the diagnostic sensitivities for both measures were low, at 52.2% and 29.2% for the Rome III and the JSIM, respectively. CONCLUSIONS: The online survey developed for this study was able to provide clarification regarding defecation patterns. The results also suggest a discrepancy between the self-recognized prevalence of constipation in Japan and prevalence of constipation based on the JSIM criteria.
		                        		
		                        		
		                        		
		                        			Asian Continental Ancestry Group
		                        			;
		                        		
		                        			Consensus
		                        			;
		                        		
		                        			Constipation*
		                        			;
		                        		
		                        			Defecation
		                        			;
		                        		
		                        			Female
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Internal Medicine
		                        			;
		                        		
		                        			Internet*
		                        			;
		                        		
		                        			Japan
		                        			;
		                        		
		                        			Male
		                        			;
		                        		
		                        			Prevalence*
		                        			;
		                        		
		                        			Sensitivity and Specificity
		                        			;
		                        		
		                        			Surveys and Questionnaires
		                        			
		                        		
		                        	
            

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