Immune checkpoint inhibitors (ICIs) have expanded therapeutic options for advanced malignancies, offering new hope for conditions once deemed untreatable. However, the advent of ICIs has introduced a spectrum of immune-related adverse events (irAEs), including leukocytoclastic vasculitis (LCV), a rare but significant complication. This case report describes development of LCV after treatment with nivolumab and ipilimumab in a 70-year-old man with malignant melanoma, highlighting the diagnostic and management challenges of such irAEs. Despite extensive investigation, conventional pathology failed to identify the immune complexes typically associated with LCV. The clinical presentation, alongside a detailed medical history and the exclusion of infections, medications, and autoimmune diseases, was crucial in establishing a diagnosis. Ulcer resolution following discontinuation of ICI therapy and initiation of steroids further support the conclusion that LCV was an irAE in this patient. This case underscores the need for vigilant monitoring for irAEs for the variable onset after ICI therapy and the importance of thorough history-taking to guide diagnosis and treatment. With ICIs becoming increasingly prevalent in oncology, the incidence of ICI-induced ulcers like LCV is expected to rise, necessitating heightened awareness and multidisciplinary approaches to patient care.

Background/Aims: Endoscopic ultrasound-guided tissue acquisition (EUS-TA) using Franseen needles is reportedly useful for its high diagnostic yield. This study compared the diagnostic yield and puncturing ability of EUS-TA using 22-gauge cobalt-chromium (CO-Cr) needles with those of stainless-steel Franseen needles in patients with solid pancreatic lesions. Methods: Outcomes were compared between the 22-gauge Co-Cr Franseen needle (December 2019 to November 2020; group C) and stainless-steel needle (November 2020 to May 2022; group S). Results: A total of 155 patients (group C, 75; group S, 80) were eligible. The diagnostic accuracy was 92.0% in group C and 96.3% in group S with no significant intergroup differences (p=0.32). The rate of change in the operator (from training fellows to experts) was 20.0% (15/75) in group C and 7.5% (6/80) in group S. Stainless-steel Franseen needles showed less inter-operator difference than Co-Cr needles (p=0.03). Conclusions Both Co-Cr and stainless-steel Franseen needles showed high diagnostic ability. Stainless-steel Franseen needles are soft and flexible; therefore, the range of puncture angles can be widely adjusted, making them suitable for training fellows to complete the procedure.

Background/Aims: Hybrid endoscopic submucosal dissection (ESD), in which an incision is made around a lesion and snaring is performed after submucosal dissection, has some advantages in colorectal surgery, including shorter procedure time and preventing perforation. However, its value for rescue resection in difficult colorectal ESD cases remains unclear. This study evaluated the utility of rescue hybrid ESD (RH-ESD). Methods: We divided 364 colorectal ESD procedures into the conventional ESD group (C-ESD, n=260), scheduled hybrid ESD group (SH-ESD, n=69), and RH-ESD group (n=35) and compared their clinical outcomes. Results: Resection time was significantly shorter in the following order: RH-ESD (149 [90–197] minutes) >C-ESD (90 [60–140] minutes) >SH-ESD (52 [29–80] minutes). The en bloc resection rate increased significantly in the following order: RH-ESD (48.6%), SH-ESD (78.3%), and C-ESD (97.7%). An analysis of factors related to piecemeal resection of RH-ESD revealed that the submucosal dissection rate was significantly lower in the piecemeal resection group (25% [20%–30%]) than in the en bloc resection group (40% [20%–60%]). Conclusions RH-ESD was ineffective in terms of curative resection because of the low en bloc resection rate, but was useful for avoiding surgery.

Endoscopic retrograde cholangiopancreatography (ERCP) in patients with surgically altered anatomy is technically challenging. For example, scope insertion, selective cannulation, and intended procedures, such as stone extraction or stent placement, can be difficult. Single-balloon enteroscopy (SBE)-assisted ERCP has been used to effectively and safely address these technical issues in clinical practice. However, the small working channel limits its therapeutic potential. To address this shortcoming, a short-type SBE (short SBE) with a working length of 152 cm and a channel of 3.2 mm diameter has recently been introduced. Short SBE facilitates the use of larger accessories to complete certain procedures, such as stone extraction or self-expandable metallic stent placement. Despite the development in the SBE endoscope, various steps have to be overcome to successfully perform such procedure. To improve success, the challenging factors of each procedure must be identified. At the same time, endoscopists need to be mindful of adverse events, such as perforation, which can arise due to adhesions specific to the surgically altered anatomy. This review discussed technical tips regarding SBE-assisted ERCP in patients with surgically altered anatomy to increase success and reduce the risk of adverse events associated with ERCP.

Purpose: To investigate the influence of multiple recurrences and repeated surgeries of Hunner lesions on bladder capacity under general anesthesia in patients with interstitial cystitis (IC). Methods: We retrospectively reviewed the clinical records of Hunner-type IC (HIC) patients who underwent transurethral fulguration or resection of Hunner lesions combined with hydrodistension by a single surgeon between 2011 and 2020. Recurrence was defined as reappearance of uncontrolled urinary symptoms in association with new Hunner lesions identified by cystoscopy. Recurrent Hunner lesions were then treated by transurethral surgeries. The recurrence-free rate, potential predictive factors of recurrence, and changes in bladder capacity under anesthesia were examined at each surgical procedure. Results: A total of 92 surgeries were performed in 47 HIC patients, 23 (49%) of whom required multiple procedures (range, 1–5 times). The mean recurrence-free time after the first surgery was 21.7 months. The recurrence-free rate was 53% at 24 months, and decreased to 32% at 48 months. There were no significant differences in age, sex, bladder capacity under anesthesia at the first surgery, duration from symptom onset to the first surgery, O’Leary-Sant questionnaire including symptom and problem indexes, visual analogue scale pain score, and the number of comorbidities between the cases with or without recurrence. Bladder capacity under anesthesia was gradually decreased as the number of surgeries was increased, and bladder capacity at the fourth procedure was significantly decreased to 80% of the capacity at the first surgery. Conclusions These results suggest that multiple recurrences and repeated surgeries of Hunner lesions result in a reduction of bladder capacity under anesthesia in HIC patients although no predictive factors for recurrence of Hunner lesions were detected.

BACKGROUND: Aging is a process that increases oxidative stress. Increased oxidative stress leads to the development of atherosclerosis and mitochondrial dysfunction. Mitochondria contribute to energy production that might have a beneficial influence on maintaining muscle strength. Therefore, the height-related single nucleotide polymorphism (SNP) rs17081935, which is also reported to be associated with mitochondrial metabolism, might be associated with reduced muscle strength and this association might be affected by atherosclerosis status. To clarify those associations, a cross-sectional study of 1374 elderly Japanese individuals aged 60-89 years was conducted. METHODS: Logistic regression was used to clarify the association between rs17081935 and reduced handgrip strength. Since atherosclerosis might affect handgrip strength, participants were stratified by atherosclerosis status. Reduced handgrip strength was defined as being in the lowest quintile of handgrip strength (< 25.6 kg for men and < 16.1 kg for women). RESULTS: No significant associations were found between a minor allele of rs17081935 and reduced handgrip strength among elderly participants without atherosclerosis. A significant inverse association was observed among elderly participants with atherosclerosis. After adjusting for known cardiovascular risk factors and height, the adjusted odd ratio (OR) and 95% confidence interval (CI) for reduced handgrip strength and a minor allele of rs17081935 were 1.13 (0.86, 1.43) for elderly participants without atherosclerosis and 0.55 (0.36, 0.86) for those with atherosclerosis, respectively. CONCLUSION A minor allele of the height-related SNP rs17081935 was significantly inversely associated with reduced handgrip strength among older individuals with atherosclerosis, but not among those without atherosclerosis.
Aged ; Aged, 80 and over ; Atherosclerosis/epidemiology* ; Body Height ; Cross-Sectional Studies ; Female ; Hand Strength ; Humans ; Japan/epidemiology* ; Male ; Middle Aged ; Polymorphism, Single Nucleotide ; Prevalence

BACKGROUND: Human T-cell leukemia virus type 1 (HTLV-1) activates inflammatory cascades by activating the NF-κB pathway. The minor allele of single nucleotide polymorphism (SNP) in breast cancer suppressor BRCA1-associated protein (BRAP), which has a common etiology with HTLV-1 infection, has been reported to be positively associated with carotid atherosclerosis, but inversely associated with hypertension. Therefore, HTLV-1 infection may be inversely associated with hypertension by activating endothelial maintenance, including atherosclerosis. To clarify these associations, a cross-sectional study was conducted using 2989 Japanese individuals aged 60-99 years participating in a general health check-up. METHODS: Logistic regression models were used to clarify the association between HTLV-1 and hypertension. Platelet levels stratified analyses were also performed since platelet production, which plays a crucial role in endothelium maintenance, can be stimulated by activating the NF-κB pathway. RESULTS: HTLV-1 infection was found to be significantly inversely associated with hypertension, particularly in subjects with high platelet levels (≥ second tertiles of platelet levels); the fully adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were 0.75 (0.62, 0.92) for total and 0.64 (0.50, 0.82) for high platelet levels, respectively. Further analysis of the non-hypertensive subjects demonstrated that HTLV-1 infection was significantly positively associated with atherosclerosis in subjects with the highest tertile of platelet levels (2.11 [1.15, 3.86]) but not in subjects with low platelet levels (first and second tertiles of platelet level) (0.89 [0.57, 1.39]). CONCLUSION Asymptomatic HTLV-1 infection is inversely associated with hypertension, possibly by activating endothelial maintenance, including atherosclerosis progression.
Aged ; Aged, 80 and over ; Carotid Artery Diseases/virology* ; Cross-Sectional Studies ; Female ; HTLV-I Infections/complications* ; Human T-lymphotropic virus 1/physiology* ; Humans ; Hypertension/virology* ; Japan/epidemiology* ; Male ; Middle Aged

BACKGROUND: Body mass-independent parameters might be more appropriate for assessing cardiometabolic abnormalities than weight-dependent indices in Asians who have relatively high visceral adiposity but low body fat. Dual-energy X-ray absorptiometry (DXA)-measured trunk-to-peripheral fat ratio is one such body mass-independent index. However, there are no reports on relationships between DXA-measured regional fat ratio and cardiometabolic risk factors targeting elderly Asian men. METHODS: We analyzed cross-sectional data of 597 elderly men who participated in the baseline survey of the Fujiwara-kyo Osteoporosis Risk in Men (FORMEN) study, a community-based single-center prospective cohort study conducted in Japan. Whole-body fat and regional fat were measured with a DXA scanner. Trunk-to-appendicular fat ratio (TAR) was calculated as trunk fat divided by appendicular fat (sum of arm and leg fat), and trunk-to-leg fat ratio (TLR) as trunk fat divided by leg fat. RESULTS: Both TAR and TLR in the group of men who used ≥ 1 medication for hypertension, dyslipidemia, or diabetes ("user group"; N = 347) were significantly larger than those who did not use such medication ("non-user group"; N = 250) (P < 0.05). After adjusting for potential confounding factors including whole-body fat, both TAR and TLR were significantly associated with low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglyceride, fasting serum insulin, and the insulin resistance index in the non-user group and non-overweight men in the non-user group (N = 199). CONCLUSION The trunk-to-peripheral fat ratio was associated with cardiometabolic risk factors independently of whole-body fat mass. Parameters of the fat ratio may be useful for assessing cardiometabolic risk factors, particularly in underweight to normal-weight populations.
Absorptiometry, Photon ; Adiposity/physiology* ; Aged ; Aged, 80 and over ; Biomarkers/metabolism* ; Cardiometabolic Risk Factors ; Cross-Sectional Studies ; Humans ; Intra-Abdominal Fat/diagnostic imaging* ; Japan ; Male ; Osteoporosis/etiology* ; Prospective Studies ; Risk Assessment ; Risk Factors ; Thorax/diagnostic imaging*

BACKGROUND: The Fujiwara-kyo Osteoporosis Risk in Men (FORMEN) study was launched to investigate risk factors for osteoporotic fractures, interactions of osteoporosis with other non-communicable chronic diseases, and effects of fracture on QOL and mortality. METHODS: FORMEN baseline study participants (in 2007 and 2008) included 2012 community-dwelling men (aged 65-93 years) in Nara prefecture, Japan. Clinical follow-up surveys were conducted 5 and 10 years after the baseline survey, and 1539 and 906 men completed them, respectively. Supplemental mail, telephone, and visit surveys were conducted with non-participants to obtain outcome information. Survival and fracture outcomes were determined for 2006 men, with 566 deaths identified and 1233 men remaining in the cohort at 10-year follow-up. COMMENTS The baseline survey covered a wide range of bone health-related indices including bone mineral density, trabecular microarchitecture assessment, vertebral imaging for detecting vertebral fractures, and biochemical markers of bone turnover, as well as comprehensive geriatric assessment items. Follow-up surveys were conducted to obtain outcomes including osteoporotic fracture, cardiovascular diseases, initiation of long-term care, and mortality. A complete list of publications relating to the FORMEN study can be found at https://www.med.kindai.ac.jp/pubheal/FORMEN/Publications.html .
Aged ; Bone Density ; Cardiovascular Diseases/etiology* ; Cohort Studies ; Geriatric Assessment ; Humans ; Independent Living ; Japan/epidemiology* ; Long-Term Care/statistics & numerical data* ; Male ; Middle Aged ; Osteoporosis/etiology* ; Osteoporotic Fractures/etiology* ; Risk Factors

BACKGROUND: A positive association between handgrip strength and blood pressure has been reported. Since these factors are linked to the condition of the endothelium, the activity of endothelial repair might influence the association between handgrip strength and hypertension. METHODS: A cross-sectional study was conducted with 257 Japanese men aged 60-69 years who underwent an annual health checkup. As individuals with high level of circulating CD34-positive cells might show active endothelial repair, which plays an important role in vascular homeostasis, participants were stratified by circulating CD34-positive cell levels, using the median value of this population (0.96 cells/μL) as the cutoff. RESULTS: Independent of known cardiovascular risk factors, for participants with a high CD34-positive cell, handgrip strength is significantly positively associated with hypertension (odds ratio and 95% confidence interval of hypertension for 1 standard deviation increment of handgrip strength were 1.85 (1.19, 2.88) but not for participants with a low CD34-positive cell (0.91 (0.61, 1.37)). CONCLUSION The positive association between handgrip strength and hypertension is limited to high CD34-positive cells. This result may help clarify the role of vascular homeostasis in maintaining muscle strength.