Hiroshima Red Cross Hospital & Atomic-bomb Survivors Hospital

Objective This study aimed to evaluate the efficacy and safety of atezolizumab plus bevacizumab (Atez+Bev) as a 2nd line therapy after the administration of durvalumab plus tremelimumab (Dur+Tre) in patients with hepatocellular carcinoma. We focused on the treatment outcomes and adverse event profiles specific to this sequential regimen. Methods A retrospective analysis was conducted on 16 patients who received 2nd line Atez+Bev after Dur+Tre therapy between April 2023 and August 2024 in our hospital and associated institutions. The objective response rate (ORR), disease control rate (DCR), treatment duration, and adverse events were assessed. Results The ORR and DCR for 2nd line Atez+Bev were 25.0% and 75.0%, respectively, thus suggesting favorable disease control. Even among patients who were non-responsive to Dur+Tre, two achieved a tumor response and eight achieved disease control. Regarding safety, pruritus was a common adverse event for both regimens. Colitis and diarrhea were more frequent in the Dur+Tre group, whereas proteinuria, hyperammonemia, and bleeding were more common in the Atez+Bev group. Conclusion This study suggests that Atez+Bev remains a viable option for patients unresponsive to Dur+Tre. Prior Dur+Tre therapy may enhance the immune response within the tumor microenvironment, thereby augmenting the efficacy of Atez+Bev. However, it is important to pay attention to the differences in adverse effect profiles between the two regimens.

Medication-related osteonecrosis of the jaw is currently classified only by clinical staging, with no imaging-based qualitative classification available. To establish foundational data for a new classification method that could help guide treatment decisions and predict prognosis, this study investigated the computed tomography findings commonly observed in patients with medication-related osteonecrosis of the jaw and their frequencies. Computed tomography scans from 784 patients across 19 medical institutions were analyzed for the presence of osteolysis, sequestrum separation, periosteal reactions, mixed-type osteosclerosis, and the bone-within-bone appearance. Clinical factors associated with each finding were also examined. Osteolysis appeared as localized in 55.1% of cases, extended in 27.7%, and advanced in 13.8%. In contrast, 3.4% of patients showed no osteolysis. This non-osteolytic pattern was more common among patients treated with denosumab. Sequestrum separation was seen in 34.7% of patients, most frequently among those with osteoporosis. Periosteal reactions were observed in 5.9% of cases as the attached type, 12.4% as the gap type, and 5.6% as the irregular type. Mixed-type osteosclerosis occurred in 31.9% of cases, most often in the mandibles of patients with malignant tumors. The bone-within-bone appearance was observed in 3.1% of cases. Patients with sequestrum separation had more favorable treatment outcomes. In contrast, those without osteolysis and those with periosteal reactions, mixed-type osteosclerosis, or bone-in-bone appearance were more likely to have poorer outcomes. This multicenter study clarified the prevalence of several key computed tomography features in medication-related osteonecrosis of the jaw, highlighting their potential relevance to clinical outcomes. These findings lay the groundwork for future research into their prognostic and therapeutic implications to support the development of a new imaging-based classification system.

ABSTRACTAims/IntroductionLittle is known about the effect of diabetologists on perioperative complication risk. Given that colorectal cancer surgery is known to carry a high complication risk among patients with diabetes, this study aimed to examine the association between the presence of diabetologists at the facility level and the risk of perioperative complications during colorectal cancer surgery.Materials and MethodsIn this retrospective cohort study, we sourced the number of board‐certified diabetologists from the Japan Diabetes Society and combined it with Diagnosis Procedure Combination (DPC) data, encompassing receipt data from acute care facilities across Japan. We used a modified Poisson model to estimate the risk of perioperative complications associated with the presence of diabetologists by adjusting for potential confounding patient and facility factors.ResultsAnalysis included 887 facilities, of which 299 (34%) had no diabetologists. A total of 24,714 patients with diabetes underwent colorectal cancer surgery between April 2018 and March 2019, with a median age of 73 years (interquartile range: 67–79 years) and 16,274 (66%) men. There were 3,165 (13%) perioperative complications. After adjustment, the risk of perioperative complications was 0.86 times (95% confidence interval: 0.77–0.96) lower in centers with at least one diabetologist than in those without a diabetologist.ConclusionsOur study suggests that the presence of a diabetologist may be important in reducing the risk of perioperative complications during colorectal cancer surgery in patients with diabetes. Future studies factoring in other facility factors and surgical types may be required to further validate our findings.

The optimal alternative donor type for patients lacking human leucocyte antigen (HLA)-matched related or unrelated donors remains unclear. In comparative studies evaluating donor types, graft-versus-host disease (GVHD)-free, relapse-free survival (GRFS) represents a well-established end-point but has limitations. The win ratio approach addresses these limitations by analysing multiple end-points with varying severities to account for the relative component priorities. We compared HLA-mismatched unrelated donors, haploidentical donors and cord blood using both the hazard ratio (HR) of GRFS and the win ratio related to GRFS. The haploidentical donor group had a similar HR of GRFS (HR: 1.01, 95% confidence interval [CI]: 0.85-1.19, p = 0.916) and win ratio (win ratio: 0.86, 95% CI: 0.72-1.02, p = 0.081) to HLA-mismatched unrelated donors. Cord blood transplantation showed similar GRFS compared to HLA-mismatched unrelated donors in the Cox proportional model (HR: 1.14, 95% CI: 0.98-1.32, p = 0.085), significantly lower win ratio (win ratio: 0.80, 95% CI: 0.68-0.93, p = 0.004) and similar outcomes to haploidentical donors. HLA-mismatched unrelated donor transplantation showed comparable to superior outcomes among alternative donor types. Our results indicate the need to present the win ratio alongside conventional methods to assess the end-point robustly.

Elevated serum IgG4 is a key diagnostic marker for type 1 autoimmune pancreatitis (AIP), but some patients lack IgG4 elevation, complicating diagnosis. This study investigated the clinicopathological features of AIP without elevated serum IgG4 levels. A total of 323 patients diagnosed with AIP at Hiroshima University Hospital and affiliated institutions were analyzed. Patients were categorized into IgG4-positive (≥ 135 mg/dL), IgG4-negative (< 135 mg/dL with “definite” or “probable” diagnosis), and possible (with “possible” diagnosis) groups. Comparative analysis was performed between the IgG4-positive (n = 281) and IgG4-negative (n = 20) groups. Segmental or focal narrowing of the main pancreatic duct (MPD) and retroperitoneal fibrosis were significantly more common in the IgG4-negative group (90.0% vs. 58.7%, P = 0.011; and 35.0% vs. 12.5%, P = 0.012, respectively). Although the number of pathological findings was comparable, the rate of surgical intervention was significantly higher in the IgG4-negative group (P < 0.001). No significant differences were observed in relapse rates or relapse sites between the two groups. These findings suggest that MPD narrowing and retroperitoneal fibrosis may be characteristic of AIP without elevated IgG4. Vigilant monitoring for relapse is warranted, regardless of serum IgG4 levels.