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Introduction Distant recurrence of non‐muscle invasive bladder cancer is a rare condition that is poorly understood and difficult to detect in follow‐up protocols. Case presentation A 73‐year‐old female with a history of T1N0M0 bladder cancer 8 years ago suffered from a left axillary tumor, a left lung tumor, left mediastinal lymph node swelling, and bilateral adrenal gland tumors. Initially, she was diagnosed with metastatic left breast cancer of the left accessory mamma by needle biopsy of an axillary tumor. Subsequent bronchoscopic biopsy of the mediastinal lymph node revealed metastatic urothelial carcinoma, although no recurrence was detected in the urinary tract. She underwent systemic therapy, and all regions shrank without reprogression. Conclusion Non‐muscle invasive bladder cancer should be managed considering distant metastasis. If the origin of the metastatic lesions is unknown, this disease should be considered as a possible origin, even in the absence of urinary tract recurrence.

Abstract Background The Cholangiocarcinoma Screening and Care Program (CASCAP) has been launched since 2013 to detect early-stage cholangiocarcinoma and reduce the disease death. However, the clinical utility of the CASCAP remains unclear. To compare survival outcomes between two time periods: before and after 2013, when significant changes in treatment strategies were implemented, and to evaluate the efficacy of the ultrasound-based screening program, in an Asian region endemic for cholangiocarcinoma. Methods A single-center retrospective review was conducted in curative-intended resection cholangiocarcinoma from 2002 to 2021. Patents characteristics and survival outcomes were compared between 2002 and 2013 (early period) and 2014 to 2021 (later period). Results A total of 1091 patients with intrahepatic (n = 624) or perihilar (n = 467) cholangiocarcinoma was included (early period, n = 658; later period, n = 433). Of 66 (15.2%) patients in the later period were referred by the CASCAP. The incidence of early-staged disease (Stage 0 and 1) was lower in early period compared to later period 16.0% versus 29.1% (p

Abstract Background Postoperative pancreatic fistula (POPF) continues to be the most common complication after distal pancreatectomy (DP). Recent advancements in surgical techniques have established minimally invasive distal pancreatectomy (MIDP) as the standard treatment for various conditions, including pancreatic cancer. However, MIDP has not demonstrated a clear advantage over open DP in terms of POPF rates, indicating the need for additional strategies to prevent POPF in MIDP. This trial (WRAP study) aims to evaluate the efficacy of wrapping the pancreatic stump with polyglycolic acid (PGA) mesh and fibrin glue in preventing clinically relevant (CR-) POPF following MIDP. Methods This multicenter, randomized controlled trial will include patients scheduled for laparoscopic or robotic DP for tumors in the pancreatic body and/or tail. Eligible participants will be centrally randomized into either the control group (Group A) or the intervention group (Group B), where the pancreatic stump will be reinforced by PGA mesh and fibrin glue. In both groups, pancreatic transection will be performed using a bioabsorbable reinforcement-attached stapler. A total of 172 patients will be enrolled across 14 high-volume centers in Japan. The primary endpoint is the incidence of CR-POPF (International Study Group of Pancreatic Surgery grade B/C). Discussion The WRAP study will determine whether the reinforcement of the pancreatic stump with PGA mesh and fibrin glue, a technique whose utility has been previously debated, could become the best practice in the era of MIDP, thereby enhancing its safety. Trial registration This trial was registered with the Japan Registry of Clinical Trials on June 15, 2024 (jRCTs032240120).

Abstract Aim Abundant data are available on the effect of the A118G (rs1799971) single‐nucleotide polymorphism (SNP) of the μ‐opioid receptor OPRM1 gene on morphine and fentanyl requirements for pain control. However, data on the effect of this SNP on intraoperative remifentanil requirements remain limited. We investigated the effect of this SNP on intraoperative remifentanil requirements. Methods We investigated 333 Japanese women, aged 21–69 years, who underwent laparoscopic gynecological surgery for benign gynecological disease under total intravenous anesthesia at Juntendo University Hospital. Average infusion rates of propofol and remifentanil during anesthesia and the average bispectral index (BIS) during surgery were recorded. Associations among genotypes of the A118G and phenotypes were examined with the Mann–Whitney U test. Results The average propofol infusion rate was not different between patients with different genotypes. The average remifentanil infusion rate was significantly higher in patients with the AG or GG genotype than the AA genotype (p = 0.028). The average intraoperative BIS was significantly higher in patients with the GG genotype than the AA or AG genotype (p = 0.039). Conclusions The G allele of the A118G SNP was associated with higher intraoperative remifentanil requirements and higher intraoperative BIS values but was not associated with propofol requirements. Given that remifentanil and propofol act synergistically on the BIS, these results suggest that the G allele of the A118G SNP is associated with lower effects of remifentanil in achieving adequate intraoperative analgesia and in potentiating the sedative effect of propofol on the BIS.

Abstract Background Difelikefalin, a potent and highly selective agonist of kappa opioid receptors, is used to treat moderate-to-severe pruritus in hemodialysis patients. Methods This was a 52-week, open-label phase 3 trial following a 6-week randomized double-blind placebo-controlled treatment period to investigate the efficacy and safety of difelikefalin in Japanese hemodialysis patients. Having completed the 6-week double-blind period, patients received difelikefalin 0.5 μg/kg three times per week intravenously for 52 weeks. Efficacies were assessed using numerical rating scale (NRS) scores, proportion of patients whose NRS score improved by ≥ 3 points and ≥ 4 points, Shiratori severity score, proportion of patients with a nighttime Shiratori severity score of ≤ 2, the Skindex-16 score, 5-D itch scale score, and patient global impression of change (PGIC). Safety was assessed on the basis of adverse events, clinical laboratory tests, vital signs, body weight, 12-lead electrocardiography, and dependency. Results The number of patients who entered the extension treatment period from the difelikefalin (MR–MR) and placebo (P-MR) groups was 85 and 83, respectively. The weekly mean NRS scores (mean ± SD) in the MR–MR group at baseline, week 6, and week 58 were 6.57 ± 1.32, 4.04 ± 2.24, and 2.36 ± 1.86, respectively. The weekly mean scores in the P-MR group, at baseline, week 6, and week 58 were 6.42 ± 1.29, 4.85 ± 1.90, and 2.73 ± 2.14, respectively. In patients receiving difelikefalin, there was a decline in the score from treatment initiation, and this decline continued until week 58. Similarly, improvements were seen until week 58 in the proportion of responders, Shiratori severity score, proportion of responders based on the Shiratori severity score, the Skindex-16 score, 5-D itch scale score, and PGIC. A correlation was seen between the change in NRS and itch-related quality of life (QOL), including the Shiratori severity score, Skindex-16 score, 5-D itch scale score, and PGIC. Difelikefalin was well tolerated and safe even when used long term. Conclusions Difelikefalin improved itching and itch-related quality of life during long-term treatment in hemodialysis patients with moderate-to-severe pruritus whose response to conventional medications had been inadequate. It also demonstrated excellent safety and tolerability. Trial registration: ClinicalTrials.gov; NCT04711603. Registered 15 January 2021, https://www.clinicaltrials.gov/study/NCT04711603?term=NCT04711603&rank=1 .

Background: Tranexamic acid (TXA) has gained popularity in spinal surgery because of its potential to reduce blood loss. However, concerns regarding its safety and efficacy remain. This systematic review and meta-analysis aimed to evaluate the efficacy of TXA in reducing blood loss and its safety profile in spinal surgeries. Methods: A comprehensive search was conducted in electronic databases for randomized controlled trials and prospective studies evaluating the use of TXA in spinal surgery. The primary outcomes were intraoperative and total estimated blood loss (EBL), and the secondary outcomes included the incidence and types of complications associated with TXA use. Meta-analyses were performed using random-effects models. Results: Thirteen studies involving 1,213 participants were included in the meta-analysis. The use of TXA was associated with significant reductions in both intraoperative (mean difference: −46.56 mL [−73.85, −19.26], p

Manabu Akazawa,1 Takahiro Sato,2 Nozomi Ebata,2 Michael LoPresti,3 Ryosuke Nishi3 1Department of Public Health and Epidemiology, Meiji Pharmaceutical University, Kiyose, Tokyo, Japan; 2Medical Affairs, Rare Disease, Pfizer Japan Inc, Shibuya-ku, Tokyo, Japan; 3Value & Access, INTAGE Healthcare Inc., Chiyoda-ku, Tokyo, JapanCorrespondence: Takahiro Sato, Pfizer Japan Inc, 3-22-7 Yoyogi, Shibuya-ku, Tokyo, 151-8589, Japan, Tel +81 90-2935-0848, Email takahiro.sato@pfizer.comBackground: About one-third of caregivers of pediatric or adolescent growth hormone deficiency (pGHD) patients in Japan have reported poor treatment adherence. However, few studies have examined factors related to adherence for that group.Objective: The aim of this study is to consider factors related to poor adherence to daily treatment among caregivers of pGHD patients in Japan.Methods: A cross-sectional survey was conducted among caregivers of pGHD patients in Japan. Caregivers were asked about demographic and treatment characteristics, health literacy, treatment satisfaction, opinions about treatment, and treatment adherence. Health literacy was assessed using the 14-item health literacy scale (HLS-14). Adherence was assessed using the 8-item Morisky Medication Adherence Scale (MMAS-8). Statistical association with adherence was considered using Chi-square and Student’s t–testing. An exploratory factor analysis (EFA) and K-means cluster analysis was conducted to consider the influence of treatment satisfaction and opinions concerning treatment on adherence.Results: Responses were collected from 112 caregivers. The caregiver’s age being 30– 39 years old, the primary caregiver being male, the primary caregiver being employed, and low functional health literacy for the caregiver were associated with poor adherence. Patients being pre-elementary school age was also associated with poor adherence. Low satisfaction with drug treatment and/or their device and communication with healthcare professionals (HCPs), and lack of agreement with the importance of treatment management (eg, keeping injection records, getting informed about the disease/therapy, reporting non-adherence, and sticking to an administration schedule), were also associated with poor adherence.Conclusion: Strategies to improve treatment adherence among caregivers of pGHD patients in Japan should consider the age, gender, and employment status of the caregiver – as well as their functional literacy. Improvement in satisfaction with the drug or device used, better communication with HCPs, and greater awareness of the importance of treatment management, may also lead to better adherence.Keywords: growth hormone, adherence, determinants, satisfaction, communication, health literacy

Abstract Fluidized granular mixtures of various particle sizes exhibit intriguing patterns as different species segregate and condense. However, understanding the segregation dynamics is hindered by the inability to directly observe the time evolution of the internal structure. We discover self-replicating bands within a quasi-2D container subjected to horizontal agitation, resulting in steady surface waves. Through direct observation of surface flow and evolving internal structures, we reveal the crucial role of coupling among segregation, surface flow, and hysteresis in granular fluidity. We develop Bonhoeffer-van der Pol type equations grounded in experimental observations, reproducing complex band dynamics, such as replication, oscillation, and breathing. It suggests the similarity between pattern formation in granular segregation and that in reaction–diffusion systems.

Abstract Background and Aims Pancreatic cancer is one of the most lethal malignancies, partly due to resistance to conventional chemotherapy. The chemoresistance of malignant tumors is associated with epithelial‐mesenchymal transition (EMT) and the stemness of cancer cells. The aim of this study is to investigate the availability and functional mechanisms of trefoil factor family 1 (TFF1), a tumor‐suppressive protein in pancreatic carcinogenesis, to treat pancreatic cancer. Methods To investigate the role of endogenous TFF1 in human and mice, specimens of human pancreatic cancer and genetically engineered mouse model of pancreatic cancer (KPC/TFF1KO; Pdx1‐Cre/LSL‐KRASG12D/LSL‐p53R172H/TFF1−/−) were analyzed by immunohistochemistry (IHC). To explore the efficacy of extracellular administration of TFF1, recombinant and chemically synthesized TFF1 were administered to pancreatic cancer cell lines, a xenograft mouse model and a transgenic mouse model. Results The deficiency of TFF1 was associated with increased EMT of cancer cells in mouse models of pancreatic cancer, KPC. The expression of TFF1 in cancer cells was associated with better survival rate of the patients who underwent chemotherapy, and loss of TFF1 deteriorated the benefit of gemcitabine in KPC mice. Extracellular administration of TFF1 inhibited gemcitabine‐induced EMT, Wnt pathway activation and cancer stemness, eventually increased apoptosis of pancreatic cancer cells in vitro. In vivo, combined treatment of gemcitabine and subcutaneous administration of TFF1 arrested tumor growth in xenograft mouse model and resulted in the better survival of KPC mice by inhibiting EMT and cancer stemness. Conclusion These results indicate that TFF1 can contribute to establishing a novel strategy to treat pancreatic cancer patients by enhancing chemosensitivity.

Corrective spine surgery for spinal deformities, such as adolescent idiopathic scoliosis (AIS) and adult spinal deformity (ASD), aims to enhance the quality of life by addressing physical impairments. However, the extent of patient satisfaction after surgery, which includes pain management, functional recovery, and psychological contentment, exhibits considerable variation across different cultural and geographical landscapes. This review describes the influence of cultural and regional disparities on postoperative satisfaction in AIS and ASD surgery with a particular emphasis on the disparities between the US and Japan. This review underscores the intricate relationship between surgical outcomes and patient-reported satisfaction metrics. The investigation reveals significant contrasts in patient satisfaction and clinical results between these 2 countries, attributed to divergent cultural expectations, lifestyle adaptations, and perceptions of bodily image. These distinctions are crucial for healthcare professionals to recognize, as they necessitate a culturally nuanced approach to patient care. This comparative review not only enhances the understanding of patient experiences across cultures but also provides valuable guidance for physicians in customizing their strategies to align with the varied expectations of their patients, thereby improving postoperative satisfaction and overall quality of life. This review emphasizes the necessity of a tailored and culturally sensitive approach to managing spinal deformities, underscoring the need to factor in cultural and regional elements to enhance patient satisfaction and surgical outcomes.

Background/Aims Since the usefulness of neoadjuvant chemo(radiation) therapy (NAT) for pancreatic cancer has been demonstrated, recurrent biliary obstruction (RBO) in patients with pancreatic cancer with a fully covered self-expandable metal stent (FCSEMS) during NAT is expected to increase. This study investigated the impact of sarcopenia on RBO in this setting. Methods Patients were divided into normal and low skeletal muscle index (SMI) groups and retrospectively analyzed. Patient characteristics, overall survival, time to RBO (TRBO), stent-related adverse events, and postoperative complications were compared between the two groups. A Cox proportional hazard model was used to identify the risk factors for short TRBO. Results A few significant differences were observed in patient characteristics, overall survival, stent-related adverse events, and postoperative complications between 38 patients in the normal SMI group and 17 in the low SMI group. The median TRBO was not reached in the normal SMI group and was 112 days in the low SMI group (p=0.004). In multivariate analysis, low SMI was the only risk factor for short TRBO, with a hazard ratio of 5.707 (95% confidence interval, 1.148–28.381; p=0.033). Conclusions Sarcopenia was identified as an independent risk factor for RBO in patients with pancreatic cancer with FCSEMS during NAT.

Background: Patterns of analgesic use before and after total joint replacement (TJR) in patients with knee/hip osteoarthritis (OA) is not well reported. Methods: This retrospective longitudinal analysis used JMDC claims data of patients who underwent knee/hip replacement surgery from 2010 to 2019. Primary outcome was proportion of patients using analgesics pre-surgery, immediately post-surgery, and in post-surgery period. Factors affecting post-surgery analgesic withdrawal and opioid prescriptions were assessed using logistic regression. Results: Of all (N = 3168) patients, those with knee OA (91.1 %) and hip OA (82.5 %) used analgesics pre-surgery, and 96.1 % with knee OA and 84.9 % with hip OA required analgesics even 3 months post-surgery. NSAIDs were most commonly used pre- and post-surgery in both OA groups. Before surgery, 15.6 % (knee OA) and 13.7 % of patients (hip OA) used weak opioids, and 23.1 % (knee OA) and 10.5 % (hip OA) of patients continued them post-surgery. Strong opioid use was noted in 2.2 % and 1.2 % of patients pre-surgery, and 5.8 % and 3.4 % of patients post-surgery in the knee and hip OA groups, respectively. Using pre-operative oral NSAIDs (odds ratio [OR]:0.56; 95 % confidence interval [CI]:0.44–0.72) and weak opioids (OR:0.58; 95 % CI:0.38–0.87) associated with withdrawal of post-surgery analgesics in patients with hip OA, and using intra-articular hyaluronic acid pre-surgery (OR:0.45; 95 % CI:0.21–0.97) was significant in patients with knee OA. Using weak (OR:4.59; 95 % CI:3.44–6.13) and strong opioids (OR:2.48; 95 % CI:1.01–6.07) pre-surgery associated with post-operative opioid use in patients with hip OA, and weak opioid use was significant in patients with knee OA (OR:7.00; 95 % CI:4.65–10.54). Conclusion: This study reported difference in analgesic use before and after TJR, and that many patients required analgesics even 3 months after TJR surgery in Japan. Pre-operative analgesic use associated with continued use after surgery. Optimal pain management before and immediately after TJR is important to reduce post-operative analgesic use, especially opioids.