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IntroductionSecondary lower extremity lymphoedema is a chronic progressive condition that frequently develops after cancer treatment and results in persistent swelling, recurrent cellulitis and impaired quality of life. Lymphaticovenous anastomosis (LVA) is an established physiological microsurgical treatment; however, postoperative outcomes vary and evidence-based adjunctive postoperative management remains limited. A novel pneumatic lymphatic drainage (PLD) system has been developed to deliver anatomically directed, pathway-aligned mechanical stimulation that mimics manual lymphatic drainage. Its clinical efficacy following LVA has not yet been evaluated in a randomised controlled trial.Methods and analysisThis multicentre, open-label, parallel-group randomised controlled trial will enrol adults (≥18 years) with unilateral secondary lower extremity lymphoedema (International Society of Lymphology stage I–II) undergoing LVA. Participants will be randomised 1:1 to receive PLD plus standard postoperative care or standard postoperative care alone. PLD will be initiated on the day of surgery and continue for 6 months (Day 183). The primary outcome is the rate of improvement in excess limb volume (EV) at Day 183 relative to baseline, calculated from circumferential measurements taken at 4 cm intervals using the truncated cone method, with the contralateral limb serving as an internal control. Secondary outcomes include longitudinal trajectories of EV, improvement in excess limb fluid volume assessed by bioimpedance, the Lymphedema Quality of Life Questionnaire, cellulitis incidence and safety outcomes. A total of 64 participants (32 per group) will provide 80% power (two-sided α=0.05) to detect a 15-percentage-point between-group difference in the rate of improvement in EV at 6 months, assuming a common SD of 20 percentage points and allowing for attrition. Primary analyses will follow the ITT principle using mixed-effects models for repeated measures.Ethics and disseminationThe study was approved by the Chiba University Certified Review Board (approval number: CRB0119-25; approval date: 15 December 2025) and was conducted in accordance with the Declaration of Helsinki and the Japanese Clinical Trials Act. Results will be disseminated through peer-reviewed publications and presentations at national and international scientific conferences, irrespective of study outcomes.Trial registrationjRCTs032250600.

Background In Japan and Europe, a retrieval basket is generally used for endoscopic extraction of bile duct stones, while in the US, a retrieval balloon is mainly used. However, the efficacies of these two devices have not been previously compared. Therefore, the present multicenter, prospective, randomized study was performed to compare the efficacies of these two devices for endoscopic biliary stone extraction. Methods This study was designed as a non-inferiority study in comparing a basket removal with a balloon removal. Six Japanese institutions participated in this study, which included 184 patients with bile duct stones < 11 mm in diameter with no limitation in the number of stones. The stones were identified and measured during ERCP, after which the patients were randomly assigned to undergo endoscopic stone extraction using either a basket catheter or a balloon catheter. The primary end point was the rate of complete removals of stones within 10 min, and the secondary end point was the rate of procedure-related complications. Results There were 91 patients in the basket group and 93 in the balloon group. The rate of successful stone extraction within 10 min was 81.3 % (74/91) in the basket group and 83.9 % (78/93) in the balloon group ( p  = 0.7000). The complication rate was 6.6 % in the basket group and 11.8 % in the balloon group ( p  = 0.3092). Complications included bleeding, pancreatitis, and cholangitis. Conclusions Basket and balloon catheters showed similar efficacies for endoscopic biliary stone extraction when stone size is 11 mm or smaller.

Background/Objectives: Although the endoscopic extended latissimus dorsi (eeLD) flap avoids dorsal scarring, a lateral thoracic incision is still required. We developed an axillary-approach endoscopic extended latissimus dorsi (Ax-eeLD) flap enabling harvest through a single 40-mm axillary incision and two 5-mm ports. This study evaluated its safety and feasibility and compared outcomes with conventional eeLD. Methods: Patients who underwent Ax-eeLD flap (study group) were retrospectively analyzed and compared with the patients who underwent conventional eeLD flap (control group, n = 15). The flap was elevated endoscopically via a single 40-mm axillary incision and two 5-mm ports, harvesting the entire latissimus dorsi muscle with its surrounding adipose tissue. Outcomes included incision length, operative time, complications, secondary fat grafting, and BREAST-Q scores. Results: Fifteen patients (post-mastectomy, n = 13; congenital hypoplasia, n = 2) underwent Ax-eeLD flap. All procedures used only the planned incisions without intraoperative complications. The study group had significantly shorter incisions than the control group (39 ± 1 mm vs. 89 ± 9 mm, p < 0.01). Operative times were similar between the groups. Eight patients developed seromas, all of which were resolved by outpatient aspiration. The frequency of postoperative cases requiring fat grafting did not differ significantly between the study and control groups (4 vs. 8; p = 0.26). BREAST-Q scores improved postoperatively and were similar between groups. Conclusions: Ax-eeLD flap enables minimally invasive harvest of the latissimus dorsi without lateral thoracic scarring. This retrospective case series supports technical feasibility and safety; further prospective studies with objective volume assessment are required.

Skin color/pigmentation is regulated through melanogenesis process in specialized melanin-producing cells, melanocytes, involving multiple signaling pathways. It is highly influenced by intrinsic and extrinsic factors such as oxidative, ultraviolet radiations and other environmental stress conditions. Besides determining the color, it governs response and tolerance of skin to a variety of environmental stresses and pathological conditions including photodamage, hyperpigmentation, and skin cancer. Depigmenting reagents have been deemed useful not only for cosmetics but also for pigmentation-related pathologies. In the present study, we attempted modulation of 1-oleoyl-2-acetyl-glycerol- (OAG-) induced melanogenesis in human melanoma and primary melanocytes. In both cell types, OAG-induced melanogenesis was associated with increase in enhanced expression of melanin, tyrosinase, as well as stress chaperones (mortalin and HSP60) and Reactive Oxygen Species (ROS). Treatment with TXC (trans-4-(Aminomethyl) cyclohexanecarboxylic acid hexadecyl ester hydrochloride) and 5/40 natural compounds resulted in their reduction. The data proposed an important role of mortalin and oxidative stress in skin pigmentation and the use of TXC and natural extracts for modulation of pigmentation pathways in normal and pathological conditions.

Background Endoscopic papillary large balloon dilation (EPLBD) is safe and effective in management of common bile duct stones (CBDS). Endoscopic sphincterotomy (EST) prior to EPLBD has been performed as a standard procedure. However, the significance of EST prior to EPLBD has not been well studied yet. Aims To compare the clinical outcomes of EPLBD with and without EST to evaluate the significance of EST. Methods Between April 2010 and March 2015, a total of 82 patients with naïve papillae underwent EPLBD with or without EST for the management of CBDS. A retrospective analysis compared the efficacy and safety of EPLBD with and without EST. Results Basic patient characteristics were not significantly different between the groups that underwent EPLBD with EST ( n  = 27) and without EST ( n  = 55). Complete stone removal rates were similar between the groups (100 % in the EST group and 98 % in the non-EST group, p  = 1.00). There was no significant difference in the median balloon size (13 mm in both groups, p  = 0.445), rate of application of mechanical lithotripsy (26 vs. 35 % in the EST and non-EST groups, respectively, p  = 0.463), or the median procedure time (38 vs. 34 min in the EST and non-EST groups, respectively, p  = 0.682). The overall adverse event rates were not statistically different (4 vs. 7 % in the EST and non-EST groups, respectively, p  = 1.00). Pancreatitis, cholangitis, and hemorrhage rates were also similar in both groups. Conclusions EST prior to EPLBD may be unnecessary since this study did not demonstrate its benefits.

Late-onset grade 4 neutropenia occurred in 3 (5.6%) of 54 non-Hodgkin's lymphoma patients treated with rituximab between September 2001 and March 2004. Neutropenia appeared 5 to 25 weeks after administration of cytotoxic agents in combination with rituximab and recurred 4 and 17 weeks after the first onset in 2 patients. Five episodes occurred in a total of 332 cycles of rituximab therapy. Bone marrow findings at the time of late-onset neutropenia showed neutrophil maturation arrest with or without reversible myeloid dysplasia in 3 episodes and selective depletion of the myeloid series in 1 episode. Neither circulating immune complexes nor antineutrophil antibodies were detected during the 3 episodes that we evaluated. Bone marrow cells stained CD8- and CD57-. Late-onset neutropenia resolved 5 to 7 days after granulocyte colony-stimulating factor therapy was started. Further studies are needed to determine how rituximab functions and to identify appropriate countermeasures.

FOLFIRINOX (FX) and gemcitabine (GEM) plus nab-paclitaxel (GnP) have been reported as effective regimens for unresectable advanced pancreatic cancer (APC). FX may be more effective but is also associated with more adverse events (AEs). Therefore, first-line treatment with FX followed by second-line GnP may be appropriate. Aims: To assess the safety and efficacy of second-line GnP for patients with APC after first-line FX failure. Methods: This study was a multicenter prospective phase II study evaluating second-line GnP in patients with APC after failed first-line FX. The primary endpoint was response rate (RR), and the secondary endpoints were overall survival (OS), progression free survival (PFS), and the frequency and degree of adverse events (AEs). Results: Thirty patients (14 male; median age, 64 years) were enrolled. The RR was 13.3%, with a median follow-up time of 9.3 months. The median OS and PFS were 7.6 and 3.8 months, respectively. From the beginning of first-line treatment, the median OS and PFS were 14.2 and 9.3 months, respectively. Grade 3 or 4 AEs were seen in 70% of patients. Conclusion: Second-line GnP after FX failure for patients with APC could be more effective than GEM alone. Further comparison studies are warranted.

In order to identify the cellular factors involved in human melanogenesis, we carried out shRNA-mediated lossof-fimction screening in conjunction with induction of melanogenesis by 1-oleoyl-2-acetyl-glycerol (OAG) in human melanoma cells using biochemical and visual assays. Gene targets of the shRNAs (that caused loss of OAG-induced melanogenesis) and their pathways, as determined by bioinformatics, revealed involvement of proteins that regulate cell stress response, mitochondrial functions, proliferation, and apoptosis. We demonstrate, for the first time, that the mitochondrial stress chaperone mortalin is crucial for melanogenesis. Upregulation of mortalin was closely associated with melanogenesis in in vitro cell-based assays and clinical samples of keloids with hyperpigmentation. Furthermore, its knockdown resulted in compromised melanogenesis. The data proposed mortalin as an important protein that may be targeted to manipulate pigmentation for cosmetic and related disease therapeutics.

The robot has recently emerged as a factor in the daily lives of humans taking the form of a mechanical pet or similar source of entertainment. A robot system that is designed to co-exist with humans, i.e., a coexistence-type robot system, is important to be “It exists in various environments with the person, and robot system by which the interaction of a physical, informational emotion with the person etc. was valued”. When studying the impact of intimacy in the humadrobot relationship, we have to examine the problems that can arise as a result of physical intimacy (coordination on safety in the hardware side and a soft side). Furthermore, the informational aspects of intimacy (recognition technology, and information transport and sharing). This paper reports the interim results of the research of a system configuration that enhances the physical intimacy relationship in the symbiosis of the human and the robot.