Fukui-ken Saiseikai Hospital

Endoscopic sphincterotomy (EST) is important in endoscopic retrograde cholangiopancreatography, but bleeding remains its common complication. This pilot study evaluated the efficacy and safety of a self-assembling peptide hydrogel (SAPH; PuraStat) in managing EST-related hemorrhage. A prospective cohort study was conducted from June 2023 to March 2024 at three hospitals in Japan, enrolling patients undergoing EST. Patients were divided into SAPH (received SAPH for EST-related bleeding) and control groups (patients without EST-related hemorrhage); primary endpoint was incidence of delayed bleeding. Of the 254 patients analyzed, 27 were in the SAPH group and 227 in the control group. Background factors related to bleeding were aligned using propensity score matching (PSM). Incidence of EST-related bleeding was 10.6% (27/254). In the SAPH group, 26 of 27 patients (96.3%) achieved successful hemostasis using SAPH alone. Although no delayed bleeding occurred in this group, it occurred in four patients in the control group (1.57%, 4/254). Other adverse events showed no significant difference between the groups. Results were similar to those after PSM and in the subgroup analysis excluding those with self-expandable metallic stent placement. SAPH is a simple, effective, and safe hemostatic option for treating EST-related hemorrhage and may be a promising first-line approach. This pilot study did not demonstrate a significant reduction in delayed bleeding, but absence of delayed bleeding in the SAPH group is noteworthy and suggests a potential preventive benefit. Thus, larger randomized controlled trials are warranted to validate these preliminary findings.

Postoperative nausea and vomiting can be a serious issue in reducing caloric intake for patients in the early stage after surgery. In Japan, ondansetron injection is now approved by insurance as a countermeasure against postoperative nausea and vomiting, but the number of reports on its effects regarding caloric intake is limited in the early stage following surgery, and opinions about the effects are divided. Thus, we examined how the effects of ondansetron administration during surgery influence caloric intake starting the day after surgery. We examined 65 patients who received a 4mg injection of ondansetron during gynecological surgery under epidural anesthesia, in comparison to 51 patients who did not receive any antiemetic. Our study was to compare the amount of caloric intake the day after surgery. The patient group who received an ondansetron injection showed higher caloric intake (1364.1 ± 55.9 vs 1188.3 ± 63.1 kcal; ANCOVA, p = 0.045). A significant increase in caloric intake was observed in patients with an Apfel Score of 3 (807 ± 62 vs 593 ± 76 kcal; p = 0.031). Our study indicated that ondansetron administration during gynecological surgery may have a positive effect on increasing postoperative caloric intake one day after surgery.

Percutaneous interventions are widely performed for bile duct injuries due to surgery, trauma, and local ablation or transarterial chemoembolization for hepatocellular carcinoma. Most bilomas can be treated with percutaneous drainage alone, but additional biliary drainage or plastic stenting in the common bile duct, dilation of the coexisting biliary stricture, or embosclerosis is also required for refractory bilomas. For bile duct occlusions or disruptions, percutaneous transhepatic biliary drainage and long-term catheter placement across the affected segment are recommended. In addition, intrahepatic biliary ablation and/or percutaneous transhepatic portal vein embolization is effective for refractory bile leaks. Percutaneous drainage is required for infected necrotized hepatocellular carcinoma due to ascending cholangitis after transarterial chemoembolization. Plastic stent placement is also recommended for main bile duct strictures caused by transarterial chemoembolization.

Oral mucositis (stomatitis) is a painful condition that affects the mouth lining. Kampo medicines (e.g., Hangeshashinto [Chinese name, Ban-Xia-Xie-Xin-Tang], Orento, and Orengedokuto) have been widely used to treat stomatitis, such as gargling with Hangeshashinto. However, the mechanisms by which Kampo medicines work are not widely understood due to their oral administration and the subsequent digestion, absorption, and metabolization of their components. Stomatitis is associated with advanced glycation end-products (AGEs) in patients with lifestyle diseases, and can be induced by both intra- and extracellular AGEs (blood and dietary AGEs). Various natural products inhibit intracellular AGE generation and suppress cytotoxicity, such as inflammation caused by extracellular AGEs. This review summarizes 19 natural products identified in the Hangeshashinto water extract and 16 natural products identified in the crude drug extract. The data show that several natural products, such as glycyrrhizin, baicalin, 6-shogaol, quercetin, epigallocatechin-3-galate, and genistein, inhibit intracellular AGEs and suppress extracellular AGE inflammation. Furthermore, several natural products in the Hangeshashito water extract can suppress cytotoxicity in stomatitis.

We herein describe an autopsy case of acute-on-chronic liver failure (ACLF) in a patient with primary biliary cholangitis (PBC) that was triggered by an exacerbation of autoimmune hepatitis (AIH)-related features. A 62-year-old woman was diagnosed as having PBC 12 years prior and had been maintained on ursodeoxycholic acid. She presented with fatigue, and was found to have acute exacerbation of liver injury. Her liver function rapidly deteriorated. Upon transfer to our hospital, she exhibited marked hyperbilirubinemia, severe coagulopathy, and ascites, which fulfilled the ACLF diagnostic criteria of the Asian Pacific association for the study of the liver (APASL). Despite intensive treatment including plasma exchange, she died on day 15 of hospitalization. Autopsy revealed advanced hepatic fibrosis with lobular distortion, chronic non-suppurative destructive cholangitis, and loss of interlobular bile ducts, which were characteristic of PBC, along with centrilobular hepatic necrosis, bridging necrosis, bile ductular proliferation, and bile plugs that were suggestive of submassive hepatic necrosis. Interface hepatitis with plasma cell infiltration was also evident. These results indicated an overlap between chronic PBC and AIH exacerbation, leading to ACLF. Our findings highlight the importance of recognizing overlap features in autoimmune liver diseases for more timely interventions and better outcomes in these complex cases.

Background and Aims: As systemic therapy for hepatocellular carcinoma (HCC) rapidly advances, eight treatment regimens are currently approved in Japan. However, the limited settings of phase III clinical trials necessitate large-scale real-world data to evaluate effective treatment sequences. To address this, we established a nationwide registry called the Hepatoma Registry of Integrating and Aggregating Electronic Health Record (HERITAGE). Approach and Results: HERITAGE, associated with a nationwide follow-up survey by the Japan Liver Cancer Association, included cases where first-line systemic therapy commenced between April 2015 and December 2022. We collected data on treatment regimens, patient demographics, effectiveness, and duration and assessed changes in regimens, trends in patient characteristics, efficacy per regimen, and cross-resistance in combinations of first- and second-line treatments. The study enrolled over 8,000 treatment lines from 5,525 cases. Chronological analysis revealed a progression in first-line treatments from sorafenib to lenvatinib and then to atezolizumab plus bevacizumab. These regimens were frequently reused in second and subsequent lines. There was an increase in older patients and those with nonviral etiologies and robust liver function. Treatments were generally initiated at earlier disease stages. Cross-resistance studies indicated that responses to second-line treatments were significantly influenced by the efficacy of first-line therapies, particularly in tyrosine kinase inhibitor sequences. Conclusions: Through establishing a comprehensive registry, this study unveiled evolving patterns in treatment regimens and shifts in patient demographics for systemic HCC therapy in Japan.

The Japanese Dermatological Association aimed to prepare a second edition of guidelines for the management of diabetic ulcer/gangrene with emphasis on the diagnosis and treatment of skin symptoms. This new edition serves as a tool to improve the quality of the diagnosis and treatment in each patient and, further, to improve the level of care for such skin conditions. All sections have been updated by collecting documents published since the publication of the first edition. In the antibacterial drug treatment for bacterial infection of ulcers, oral administration was added after consideration. In the treatment of antibacterial drugs for bacterial infection of ulcers, not only infusion but also oral administration was mentioned. In addition, clinical questions (CQs) for imaging tests for diagnosing ischemia of the limbs were newly created. The titles of some CQs were changed to conform to the actual clinical setting. (i) The content has been updated by adding and collecting documents for all sections; (ii) we have additionally included oral antibiotic treatment for bacterial infection of ulcers; (iii) we have added CQs pertaining to imaging tests for diagnosing ischemia of the limbs; and (iv) we have revised the titles of some CQs to conform to the actual clinical setting. In particular, the recommendation levels of dressing materials newly covered by Japanese national health insurance are mentioned. In addition, CQs regarding the initial treatment of electrical (CQ15) and chemical burns (CQ16), and the use of escharotomy (CQ22) have been created.

Endoscopic ultrasound-guided fine-needle aspiration/biopsy (EUS-FNA/B) is critical for determining treatment strategies for patients with pancreatic cancer. However, conventional pathological examination using hematoxylin and eosin (H&E) staining is time-consuming. Microscopy with ultraviolet surface excitation (MUSE) enables rapid pathological diagnosis without requiring slide preparation. This study explores the potential of combining MUSE imaging with a cycle-consistent generative adversarial network (CycleGAN), an image generation algorithm capable of learning translations without paired images, to enhance diagnostic workflows for pancreatic EUS-FNA/B. Thirty-five pancreatic specimens were stained with Terbium/Hoechst 33342, and deep ultraviolet (DUV) fluorescence images were captured by exciting the tissue surface. These fluorescence images, along with H&E-stained formalin-fixed, paraffin-embedded (FFPE) sections from the same specimens, were divided into 256 × 256-pixel segments for CycleGAN training. The algorithm was employed to translate pseudo-H&E images from MUSE test images. The pseudo-H&E images generated by the CycleGAN showed improved inter-pathologist agreement among three pathologists compared with the original MUSE images. We established a technique to perform MUSE imaging on small pancreatic samples obtained through EUS-FNA/B and confirmed that H&E-style translation using CycleGAN simplified interpretation for pathologists. Integrating MUSE imaging with CycleGAN has the potential to offer a rapid, cost-effective, and accurate diagnostic tool.

Clinical trials rarely focus on elder patients with castration-resistant prostate cancer (CRPC), and data on the outcomes of second-generation androgen receptor signaling inhibitors (ARSIs) remain limited. The ENABLE study for prostate cancer was an investigator-initiated, multicenter, randomized controlled trial conducted in Japan to compare enzalutamide (ENZ) and abiraterone plus prednisolone (ABI). This sub-analysis was performed to evaluate the efficacy and the safety profiles between patients aged ≥ 75 (older) and < 75 years (younger), and then between the ENZ and ABI arms in the older and the younger cohort separately. The ENZ arm included 41 younger and 51 older patients, while the ABI arm included 36 younger and 56 older patients. No significant differences in survival endpoints were observed between younger and older patients. Median time to prostate-specific antigen (PSA) progression (TTPP) was 15.2 months for younger and 21.2 months for older patients (HR 0.84, 95% CI 0.53-1.33, p = 0.4647). Median overall survival (OS) was 33.7 months for younger and 37.8 months for older patients (HR 0.80, 95% CI 0.50-1.29, p = 0.3651). Among older patients (n = 107), the ENZ arm had a TTPP of 21.2 months compared to 10.1 months for the ABI arm and an OS of 37.8 months compared to 44.7 months for the ABI arm (p = 0.1506 and p = 0.9321, respectively). Any grade and grade ≥ 3 adverse events were observed in 47 (61%) and 11 (14%) younger patients and 73 (68%) and 18 (17%) older patients, respectively. No significant differences were found in any grade or grade ≥ 3 adverse events between younger and older patients (p = 0.3487 and p = 0.6885, respectively). ARSIs demonstrated similar efficacy and safety in both younger and older patients. ENZ may be a more suitable option for older patients due to its higher PSA response rate. This trial was registered with the University Hospital Medical Information Network (UMIN) Center under identifier UMIN000015529.