BACKGROUND: Mitochondria, which harbor their own genome (mtDNA), have attracted attention due to the potential of mtDNA copy number (mtDNA-CN) as an indicator of mitochondrial dysfunction. Although mtDNA-CN has been proposed as a simple and accessible biomarker for metabolic disorders such as metabolic dysfunction-associated steatotic liver disease, the underlying mechanisms and the causal relationship remain insufficiently elucidated. In this investigation, we combined longitudinal epidemiological data, animal studies, and in vitro assays to elucidate the potential causal relationship between reduced mtDNA-CN and the development of steatotic liver disease (SLD). METHODS: We conducted a longitudinal study using data from a health examination cohort initiated in 1981 in Yakumo, Hokkaido, Japan. Data from examinations performed in 2015 and 2022 were analyzed, focusing on 76 subjects without SLD at baseline (2015) to assess the association between baseline mtDNA-CN and subsequent risk of SLD development. In addition, 28-day-old SD rats were fed ad libitum on a 45% high-fat diet and dissected at 2 and 8 weeks of age. Blood and liver mtDNA-CN were measured and compared at each feeding period. Additionally, in vitro experiments were performed using HepG2 cells treated with mitochondrial function inhibitors to induce mtDNA-CN depletion and to examine its impact on intracellular lipid accumulation. RESULTS: Epidemiological analysis showed that the subjects with low mtDNA-CN had a significantly higher odds ratio for developing SLD compared to high (odds ratio [95% confidence interval]: 4.93 [1.08-22.50]). Analysis of the animal model showed that 8 weeks of high-fat diet led to the development of fatty liver and a significant decrease in mtDNA-CN. A further 2 weeks of high-fat diet consumption resulted in a significant decrease in hepatic mtDNA-CN, despite the absence of fatty liver development, and a similar trend was observed for blood. Complementary in vitro experiments revealed that pharmacologically induced mitochondrial dysfunction led to a significant reduction in mtDNA-CN and was associated with increases in intracellular lipid accumulation in HepG2 cells. CONCLUSIONS Our findings suggest that reduced mtDNA-CN may contribute causally to SLD development and could serve as a convenient, noninvasive biomarker for early detection and risk assessment.
Animals ; DNA, Mitochondrial/genetics* ; Humans ; Male ; DNA Copy Number Variations ; Female ; Fatty Liver/blood* ; Rats ; Middle Aged ; Longitudinal Studies ; Rats, Sprague-Dawley ; Adult ; Japan/epidemiology* ; Aged ; Biomarkers/blood* ; Hep G2 Cells ; Diet, High-Fat/adverse effects*

BACKGROUND: Although serum carotene may contribute to dementia prevention, there is a lack of longitudinal evidence for early cognitive decline before dementia symptoms. The aim of this study was to examine whether serum carotene levels were associated with annually evaluated cognitive trajectories among the Japanese general population. METHODS: Among 581 baseline participants, 199 individuals (83 males; mean age [min, max], 62.7 [39, 90] years) who underwent cognitive assessments more than twice after baseline were analyzed. "Attention" levels were assessed using one- and three-target Digit Cancellation Tests (D-CAT1 and D-CAT3). "General cognitive ability" was assessed by the short version of Mini-Mental State Examination (SMMSE). Serum carotenes (α-carotene, β-carotene and lycopene) were measured by high-performance liquid chromatography. After the measurements, we calculated total carotene levels by summing up the levels of all measured carotene. Carotene levels were categorized into three groups for analysis (low: 0%-25%, middle: 25%-75%, and high: 75%-100%). A linear mixed model was used to estimate the slope of the D-CAT score trajectory and to compare it between three categories. RESULTS: Compared with the middle carotene group, decline of attention was faster in the D-CAT1 for low β-carotene (β = -3.48, p = 0.035), lycopene (β = -3.10, p = 0.062), and total carotene (β = -4.75, p = 0.003), but not for α-carotene (β = -2.60, p = 0.111). For the D-CAT3, decline of attention was faster in the group of low lycopene (β = -3.17, p = 0.002) and total carotene (β = -2.17, p = 0.037) compared with the middle carotene group, while no clear association for α-carotene (β = -0.67, p = 0.521) and β-carotene (β = -0.64, p = 0.639). There were no clear associations between serum carotene and the SMMSE score. CONCLUSIONS These findings suggest low levels of serum lycopene are associated with a decline of attention in the setting of the general population.
Humans ; Male ; Carotenoids/blood* ; Female ; Longitudinal Studies ; Middle Aged ; Japan ; Aged ; Adult ; Aged, 80 and over ; Attention ; Lycopene ; East Asian People

The patient was a 66-year-old man who presented to our hospital with intermittent abdominal pain. Abdominal ultrasound showed a mass presenting as a target sign in the right abdomen, suggesting intussusception. Subsequent computed tomography (CT) and lower gastrointestinal endoscopy revealed a 5 cm lipoma in the ascending colon. The intussusception had resolved spontaneously, so the patient was followed up on an outpatient basis. Although endoscopic treatment was considered for the lipoma, due to its large size, the patient was referred to our department for surgery 1 month later. A follow-up CT scan revealed a recurrence of the intussusception. Because the patient tolerated oral intake, had normal bowel movements without symptoms of bowel obstruction, and experienced only mild abdominal pain, conservative outpatient observation was continued until laparoscopic-assisted ileocecal resection was performed. The postoperative course was uneventful, and the patient was discharged on postoperative day 8 without any complications. Colonic lipoma causing intussusception is relatively rare. Since lipoma is a benign disease, it is a good candidate for laparoscopic surgery, which offers excellent cosmetic outcomes and rapid postoperative recovery. Even in cases with intussusception, when there is no bowel obstruction and the abdominal pain is mild, elective surgery within 1-3 months can be considered a viable option.

Metronidazole is an effective antibacterial agent against anaerobic bacteria, and its use in the gastrointestinal field, particularly in patients with intra-abdominal infections, has increased with the availability of injectable formulations. However, a known side effect of metronidazole is central nervous system impairment, namely, metronidazole-induced encephalopathy. Here, we present a case of a 68-year-old man who underwent laparoscopic abdominoperineal resection for rectal cancer in March of year X. Postoperatively, metronidazole was administered for pelvic dead space infection and perineal wound infection, and the patient continued the oral medication after discharge. In May of year X, the patient was referred to our institution near his home for postoperative adjuvant chemotherapy. In February of year X+1, the patient developed dysarthria, and a FLAIR (fluid-attenuated inversion recovery) image on head magnetic resonance imaging revealed bilaterally symmetric hyperintense lesions in the dentate nuclei of the cerebellum. Suspecting metronidazole-induced encephalopathy based on the medication history, metronidazole was discontinued, leading to symptom improvement within approximately 3 days. We diagnosed metronidazole-induced encephalopathy based on the imaging findings and clinical observations. When using metronidazole, we should pay attention to the dosage and duration of administration and make efforts to detect side effects early.

Objective: In Japan, perioperative prophylaxis of pulmonary embolism (PE) in gynecologic cancer patients with preoperative asymptomatic venous thromboembolism (VTE) has not been well established yet. The GOTIC-VTE trial was a prospective, multi-center, single-arm clinical trial to investigate the prevention of postoperative symptomatic PE onset by seamless anticoagulant therapy from the preoperative period to 4 weeks after surgery instead of using intermittent pneumatic compression. Methods: Anticoagulant therapy was started immediately after asymptomatic VTE diagnosis and stopped preoperatively according to the rules of each institution. Unfractionated heparin administration was resumed within 12 hours postoperatively, and this was followed by the switch to low-molecular-weight heparin and subsequently, edoxaban; this cycle was continued for 28 days. Primary outcome was the occurrence of symptomatic PE in 28 days postoperatively. Secondary outcomes were the incidence of VTE-related events in 28 days and 6 months postoperatively and protocol-related adverse events. Results: Between February 2018 and September 2020, 99 patients were enrolled; of these, 82patients were assessed as the full analysis set, including 58 for ovarian cancer, fallopian tube, or peritoneal cancer; 21 for endometrial cancer; and 3 for cervical cancer. No symptomatic PE was observed within 28 days postoperatively; two patients had bleeding events (major bleeding and clinically relevant nonmajor bleeding) and three had grade 3 adverse events (increased alanine transaminase, aspartate aminotransferase, or gamma-glutamyl transferase). Conclusion The multifaceted perioperative management for gynecologic malignancies with asymptomatic VTE effectively prevented postoperative symptomatic PE.Trial Registration: JRCT Identifier: jRCTs031180124

Objective: In Japan, perioperative prophylaxis of pulmonary embolism (PE) in gynecologic cancer patients with preoperative asymptomatic venous thromboembolism (VTE) has not been well established yet. The GOTIC-VTE trial was a prospective, multi-center, single-arm clinical trial to investigate the prevention of postoperative symptomatic PE onset by seamless anticoagulant therapy from the preoperative period to 4 weeks after surgery instead of using intermittent pneumatic compression. Methods: Anticoagulant therapy was started immediately after asymptomatic VTE diagnosis and stopped preoperatively according to the rules of each institution. Unfractionated heparin administration was resumed within 12 hours postoperatively, and this was followed by the switch to low-molecular-weight heparin and subsequently, edoxaban; this cycle was continued for 28 days. Primary outcome was the occurrence of symptomatic PE in 28 days postoperatively. Secondary outcomes were the incidence of VTE-related events in 28 days and 6 months postoperatively and protocol-related adverse events. Results: Between February 2018 and September 2020, 99 patients were enrolled; of these, 82patients were assessed as the full analysis set, including 58 for ovarian cancer, fallopian tube, or peritoneal cancer; 21 for endometrial cancer; and 3 for cervical cancer. No symptomatic PE was observed within 28 days postoperatively; two patients had bleeding events (major bleeding and clinically relevant nonmajor bleeding) and three had grade 3 adverse events (increased alanine transaminase, aspartate aminotransferase, or gamma-glutamyl transferase). Conclusion The multifaceted perioperative management for gynecologic malignancies with asymptomatic VTE effectively prevented postoperative symptomatic PE.Trial Registration: JRCT Identifier: jRCTs031180124

Objective: In Japan, perioperative prophylaxis of pulmonary embolism (PE) in gynecologic cancer patients with preoperative asymptomatic venous thromboembolism (VTE) has not been well established yet. The GOTIC-VTE trial was a prospective, multi-center, single-arm clinical trial to investigate the prevention of postoperative symptomatic PE onset by seamless anticoagulant therapy from the preoperative period to 4 weeks after surgery instead of using intermittent pneumatic compression. Methods: Anticoagulant therapy was started immediately after asymptomatic VTE diagnosis and stopped preoperatively according to the rules of each institution. Unfractionated heparin administration was resumed within 12 hours postoperatively, and this was followed by the switch to low-molecular-weight heparin and subsequently, edoxaban; this cycle was continued for 28 days. Primary outcome was the occurrence of symptomatic PE in 28 days postoperatively. Secondary outcomes were the incidence of VTE-related events in 28 days and 6 months postoperatively and protocol-related adverse events. Results: Between February 2018 and September 2020, 99 patients were enrolled; of these, 82patients were assessed as the full analysis set, including 58 for ovarian cancer, fallopian tube, or peritoneal cancer; 21 for endometrial cancer; and 3 for cervical cancer. No symptomatic PE was observed within 28 days postoperatively; two patients had bleeding events (major bleeding and clinically relevant nonmajor bleeding) and three had grade 3 adverse events (increased alanine transaminase, aspartate aminotransferase, or gamma-glutamyl transferase). Conclusion The multifaceted perioperative management for gynecologic malignancies with asymptomatic VTE effectively prevented postoperative symptomatic PE.Trial Registration: JRCT Identifier: jRCTs031180124

Background/Aims: Diagnosis of Helicobacter pylori-naïve gastric cancer (HPNGC) is becoming increasingly important. This study aimed to explore the quality indicators for HPNGC detection. Methods: We conducted a cross-sectional, nationwide, web-based survey of gastrointestinal endoscopists in Japan. In addition to questions about the number of HPNGC cases detected in a year and basic information, the questionnaire also consisted of 28 questions: (1) 18 about HPNGC awareness, (2) six about diagnostic proactiveness, and (3) four about interest in HPNGC. Results: Valid responses were obtained from 712 endoscopists. The Japan Gastroenterological Endoscopy Society-certified endoscopists had a significantly higher HPNGC detection rate than the nonspecialists (0.42% vs. 0.32%, respectively; p=0.008). The results of the multiple regression analysis showed that Japan Gastroenterological Endoscopy Society certification and high awareness and interest scores were independent predictors of the HPNGC detection rate (p=0.012, p<0.001, p=0.024, respectively). Principal component analysis showed that the endoscopists who attended conferences for collecting information on HPNGC had a higher level of awareness. Conclusions To improve the detection of HPNGC, it is necessary to increase the awareness of the disease. It is hoped that relevant societies will play an important role in endoscopists’ education.

A 70-years-old woman who had been on hemodialysis for 8 years was referred to our institution to undergo mitral surgery for mitral valve stenosis. Intraoperative investigations confirmed severe calcification of the posterior mitral leaflet and all-around mitral annulus. We excised the mitral leaflet using the Ultrasonic Surgical System and preserved the calcified annulus to prevent a fatal complication such as left ventricular rupture. We passed 2-0 polyester mattress sutures through the calcified annulus from the left ventricle to the left atrium, and mitral valve replacement was performed using a reversed 19 mm On-X mechanical heart valve for the aortic valve. The postoperative course was uneventful. Mitral annular calcification is a factor of fatal complications such as left ventricle rupture and coronary artery injury. We succeeded in preserving the calcified annulus and using a small diameter mechanical heart valve.

Background: The palliative care unit (PCU) at the National Cancer Center Hospital East changed the administrative policy to strengthen the transition to palliative home care. This study aimed to identify the factors tended to transfer to palliative home care in Japan. Methods: We reviewed the medical records of consecutive cancer patients admitted to our PCU during period from October 2010 until September 2011. Patients with performance status 4 and duplication were excluded in this study. We identified variables associated with the discharged group and the others group, using the univariate and multivariate analyses. Results: There were 223 patients (Pts) during periods, 63 Pts (28.3%) discharged to palliative home care and 160 Pts (71.7%) deceased in our PCU. Univariate and multivariate analysis identified: admission from their own home, a good PS of ≤ 2, good oxygen saturation, a good amount of oral intake, maintain of PS at day 15, no dyspnea and no abdominal distention as predictions of a transition to home from our PCU. Conclusion: Our study indicated the factors tended to transfer to palliative home care from PCU in Japan, however this study had some limitations. A prospective study is required to validate these factors.