Background/Aims: Despite the advent of advanced therapies, cases of so-called “difficult-to-treat” (D2T) ulcerative colitis (UC) persist. This study aims to clarify the epidemiological and clinical characteristics of patients with D2T UC. Methods: We conducted a nested case-control study using the Medical Data Vision Claims Database in patients with UC who began an advanced therapy (biologics, advanced small molecules, calcineurin inhibitors) from January 2018 through April 2023. D2T UC patients were defined as having 2 or more switches of advanced therapies, or as undergoing surgery for UC, within 2 years after the first advanced therapy. Results: Four hundred and one (16.7%) and 1,996 patients (83.3%) met the definitions of patients with D2T UC and non-D2T UC, respectively. After 1:1 matching by index year, 355 patients per group were included in the analysis. Multivariate logistic regression analyses, including sensitivity analyses based on follow-up period after the first advanced therapy, showed that a prescribed corticosteroid dose of ≥ 30 mg/day during the 6-month baseline period was associated with D2T UC. In D2T UC patients, median duration of the first advanced therapy was 99 days, and median number of advanced therapies per year was 1.7. The first advanced therapy was continued for 2 years in 78% of patients with non-D2T UC. Conclusions The proportion of D2T UC patients among UC patients starting advanced therapy was 16.7%. The factor most associated with D2T UC was the need for a corticosteroid dose ≥ 30 mg/day during the 6 months before initiation of advanced therapy.

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.

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*

Objective: To evaluate and compare the perioperative and oncologic outcomes of laparoscopic and robotic-assisted surgeries in patients with low-risk endometrial cancer who underwent minimally invasive surgery (MIS) for complete surgical staging, including sentinel lymph node mapping. Methods: A retrospective study included 190 patients diagnosed with low-risk endometrial cancer who underwent MIS combined with sentinel lymph node navigation surgery (SNNS) between December 2016 and December 2021. Among these patients, 66 underwent laparoscopic surgery, while 124 underwent robotic-assisted surgery. The analysis focused on patient characteristics, perioperative outcomes, and prognostic factors, including recurrencefree survival (RFS) and overall survival (OS). Statistical analysis was performed using Kaplan–Meier survival curves and appropriate comparative tests for outcome evaluation. Results: The median operative time and estimated blood loss were significantly longer and greater in the robotic surgery group than in the laparoscopic group (209.5 vs. 157.5 min, 20 vs. 5 mL, respectively). The identification rates of sentinel nodes were 97% and 95.2% in the laparoscopic and robotic groups, respectively, with no significant difference between the 2.Recurrence was observed in two and three cases in the laparoscopic robotic surgery groups, respectively. The 3-year RFS rates were 97.6% (95% confidence interval [CI]=0.8482–0.9769) and 93.9% (95% CI=0.9277–0.9922) for the robotic and laparoscopic groups, respectively, while the 3-year OS rates were 99.2% (95% CI=0.8561–0.9902) and 96.1% (95% CI=0.9450– 0.9989), respectively, with no statistically significant differences. Conclusion MIS combined with SNNS is a highly effective approach for managing low-risk endometrial cancer, providing comparable oncologic outcomes to laparoscopy while enhancing the quality of life of patients.

Purpose: The prognosis for patients with metastatic renal cell carcinoma (RCC) has markedly improved with the advent of molecular targeted agents and immune checkpoint inhibitors. However, few studies have reported the outcomes of systemic therapy in metastatic RCC patients undergoing dialysis. This study aimed to evaluate the clinical outcomes of systemic therapy for metastatic RCC patients on dialysis. Materials and Methods: We retrospectively reviewed 253 patients with metastatic RCC (17 on dialysis and 236 not on dialysis) who received systemic therapy at Keio University Hospital in Japan. Progression-free survival (PFS), overall survival (OS), and cancer-specific survival (CSS) were assessed using the Kaplan-Meier method. Results: Clear cell RCC was diagnosed pathologically in 52.9% of dialysis patients and 82.6% of nondialysis patients (p=0.007). Among dialysis patients, 58.8% were classified as intermediate risk and 41.2% as poor risk. Regarding first-line therapy, 4 dialysis patients received cytokine therapy, 11 received tyrosine kinase inhibitors, 1 received mammalian target of rapamycin inhibitors, and 1 received immune checkpoint inhibitors. The median PFS (6.9 months, p<0.001), OS (21.2 months, p=0.001), and CSS (29.1 months, p=0.003) were all significantly shorter in dialysis patients. After propensity score matching, no significant difference was observed in PFS. However, significant differences persisted in OS and CSS between the dialysis and nondialysis groups. Conclusion Both OS and CSS were significantly shorter in dialysis patients with metastatic RCC compared to those not on dialysis.

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.