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*

Methods: Forty-nine adults who underwent single-level L4/5 interbody fusion for degenerative spondylolisthesis were divided into BE-ELIF (n=27) and OLIF (n=22) groups based on the surgical approach used. Clinical outcomes were assessed using the Visual Analog Scale and the Japanese Orthopedic Association Back Pain Evaluation Questionnaire (JOABPEQ). Radiographic parameters, including distance of spondylolisthesis, disc height, segmental lordosis, lumbar lordosis, pelvic tilt, and sagittal vertical axis, were evaluated preoperatively and at final follow-up. Results: OLIF provided significantly better relief of pain in lower limbs and buttocks at 1-year follow-up. No significant between-group differences were observed in JOABPEQ domains. BE-ELIF resulted in greater improvements in spondylolisthesis distance and disc height, while other parameters did not differ significantly between the two groups. Conclusions For L4/5 degenerative spondylolisthesis, BE-ELIF demonstrated superior spondylolisthesis reduction and disc height improvement than OLIF. Although BE-ELIF was associated with some inferior clinical outcomes, it provided satisfactory results, effective realignment, and a low complication risk.

Methods: Forty-nine adults who underwent single-level L4/5 interbody fusion for degenerative spondylolisthesis were divided into BE-ELIF (n=27) and OLIF (n=22) groups based on the surgical approach used. Clinical outcomes were assessed using the Visual Analog Scale and the Japanese Orthopedic Association Back Pain Evaluation Questionnaire (JOABPEQ). Radiographic parameters, including distance of spondylolisthesis, disc height, segmental lordosis, lumbar lordosis, pelvic tilt, and sagittal vertical axis, were evaluated preoperatively and at final follow-up. Results: OLIF provided significantly better relief of pain in lower limbs and buttocks at 1-year follow-up. No significant between-group differences were observed in JOABPEQ domains. BE-ELIF resulted in greater improvements in spondylolisthesis distance and disc height, while other parameters did not differ significantly between the two groups. Conclusions For L4/5 degenerative spondylolisthesis, BE-ELIF demonstrated superior spondylolisthesis reduction and disc height improvement than OLIF. Although BE-ELIF was associated with some inferior clinical outcomes, it provided satisfactory results, effective realignment, and a low complication risk.

Methods: Forty-nine adults who underwent single-level L4/5 interbody fusion for degenerative spondylolisthesis were divided into BE-ELIF (n=27) and OLIF (n=22) groups based on the surgical approach used. Clinical outcomes were assessed using the Visual Analog Scale and the Japanese Orthopedic Association Back Pain Evaluation Questionnaire (JOABPEQ). Radiographic parameters, including distance of spondylolisthesis, disc height, segmental lordosis, lumbar lordosis, pelvic tilt, and sagittal vertical axis, were evaluated preoperatively and at final follow-up. Results: OLIF provided significantly better relief of pain in lower limbs and buttocks at 1-year follow-up. No significant between-group differences were observed in JOABPEQ domains. BE-ELIF resulted in greater improvements in spondylolisthesis distance and disc height, while other parameters did not differ significantly between the two groups. Conclusions For L4/5 degenerative spondylolisthesis, BE-ELIF demonstrated superior spondylolisthesis reduction and disc height improvement than OLIF. Although BE-ELIF was associated with some inferior clinical outcomes, it provided satisfactory results, effective realignment, and a low complication risk.

Methods: This study included 4,653 adult patients with a definitive diagnosis of CFD from the DPC database. The database contains nationwide inpatient data collected from >1,000 acute care hospitals in Japan. The DPC database contains information regarding hospitalization, such as diagnosis, treatment, medical history, complications, and hospitalization outcomes. This study identified 460 pairs of patients after one-to-one propensity-score matching (PSM). Treatment outcomes were compared between patients who underwent surgery for CFD within 72 hours (early group) and later (delayed group) after admission. The main outcomes included 30-day mortality, inhospital death, and major complications. The secondary outcomes were improvement in the Barthel index, length of hospital stay, and discharged home rate. Results: After adjusting for PSM, the early group had a significantly higher 30-day mortality rates than the delayed group (3.0% vs. 0.4%, p=0.006). In the multivariate logistic regression analysis after PSM, the early group was associated with an increased risk of 30-day mortality (odds ratio, 8.05; 95% confidence interval, 2.15–5.26; p=0.007). Conclusions This study indicated that early surgery for CFD resulted in increased 30-day mortality.

Benign biliary stricture (BBS) is a complication of chronic pancreatitis (CP). Despite endoscopic biliary stenting, some patients do not respond to treatment, and they experience recurrent cholangitis. We report two cases of CP with refractory BBS treated using endoscopic ultrasound-guided choledochoduodenostomy (EUS-CDS) fistula creation. A 50-year-old woman and a 60-year-old man both presented with obstructive jaundice secondary to BBS due to alcoholic CP. They underwent repeated placement of a fully covered self-expandable metal stent for biliary strictures. However, the strictures persisted, causing repeated episodes of cholangitis. Therefore, an EUS-CDS was performed. The stents were eventually removed and the patients became stent-free. These fistulas have remained patent without cholangitis for more than 2.5 years. Fistula creation using EUS-CDS is an effective treatment option for BBS.

Background/Aims: Endoscopic ultrasound (EUS)-guided hepaticogastrostomy (EUS-HGS) performed at the intrahepatic bile duct segment 3 (B3) is widely used for biliary drainage. Although performing post-puncture procedures is easier in the intrahepatic bile duct segment 2 (B2) when using a conventional oblique-viewing (OV) EUS scope, this method may cause transesophageal puncture and severe adverse events. We evaluated the safety and efficacy of B2 puncture using a novel OV-EUS scope. Methods: In this single-center retrospective study, we prospectively enrolled and collected data from 45 patients who consecutively underwent EUS-HGS procedures with a novel OV-EUS scope between September 2021 and December 2022 at our cancer center. Results: The technical success rates of B2-EUS-HGS and EUS-HGS were 93.3% (42/45) and 97.8% (44/45), respectively. The early adverse event rate was 8.9% (4/45) with no cases of scope changes or transesophageal punctures. The median procedure time was 13 minutes (range, 5–30). Conclusions B2-EUS-HGS can be performed safely with the novel EG-740UT (Fujifilm) OV-scope without transesophageal puncture and with a high success rate. B2-EUS-HGS using this novel OV scope may be the preferred strategy for EUS-HGS.

Background/Aims: Endoscopic ultrasound (EUS)-guided hepaticogastrostomy (EUS-HGS) is useful for patients with biliary cannulation failure or inaccessible papillae. However, it can lead to serious complications such as bile peritonitis in patients with ascites; therefore, development of a safe method to perform EUS-HGS is important. Herein, we evaluated the safety of EUS-HGS with continuous ascitic fluid drainage in patients with ascites. Methods: Patients with moderate or severe ascites who underwent continuous ascites drainage, which was initiated before EUS-HGS and terminated after the procedure at our institution between April 2015 and December 2022, were included in the study. We evaluated the technical and clinical success rates, EUS-HGS-related complications, and feasibility of re-intervention. Results: Ten patients underwent continuous ascites drainage, which was initiated before EUS-HGS and terminated after completion of the procedure. Median duration of ascites drainage before and after EUS-HGS was 2 and 4 days, respectively. Technical success with EUS-HGS was achieved in all 10 patients (100%). Clinical success with EUS-HGS was achieved in 9 of the 10 patients (90 %). No endoscopic complications such as bile peritonitis were observed. Conclusions In patients with ascites, continuous ascites drainage, which is initiated before EUS-HGS and terminated after completion of the procedure, may prevent complications and allow safe performance of EUS-HGS.

Background/Aims: Endoscopic ultrasound-guided tissue acquisition (EUS-TA) is a standard diagnostic method for biliary tract cancer (BTC), and samples obtained in this manner may be used for comprehensive genomic profiling (CGP). This study evaluated the utility of EUS-TA for CGP in a clinical setting and determined the factors associated with the adequacy of CGP in patients with BTC. Methods: CGP was attempted for 105 samples from 94 patients with BTC at the Aichi Cancer Center, Japan, from October 2019 to April 2022. Results: Overall, 77.1% (81/105) of the samples were adequate for CGP. For 22-G or 19-G fine-needle biopsy (FNB), the sample adequacy was 85.7% (36/42), which was similar to that of surgical specimens (94%, p=0.45). Univariate analysis revealed that 22-G or larger FNB needle usage (86%, p=0.003), the target primary lesions (88%, p=0.015), a target size ≥30 mm (100%, p=0.0013), and number of punctures (90%, p=0.016) were significantly positively associated with CGP sample adequacy. Conclusions EUS-TA is useful for CGP tissue sampling in patients with BTC. In particular, the use of 22-G or larger FNB needles may allow for specimen adequacy comparable to that of surgical specimens.