Onomichi General 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.

Recent studies have demonstrated that breast pathological complete response (pCR) can be accurately diagnosed preoperatively using image-guided needle biopsy after neoadjuvant chemotherapy (NAC), underscoring the value of incorporating ypT stage into prediction models for axillary response (ypN0). Based on this evidence, we developed and externally validated a nomogram to predict ypN0 in patients with clinically node-positive (cN+) breast cancer treated with NAC. This retrospective, multicenter study included 609 patients with cN + breast cancer who underwent NAC followed by surgery. A nomogram was developed using a training cohort (n = 330) and validated in an independent cohort (n = 279). Diagnostic performance was evaluated using the area under the receiver operating characteristic curve (AUC), calibration plots, decision curve analysis (DCA), and positive predictive value (PPV). The nomogram incorporated five predictors: ypT stage, cN stage, hormone receptor status, HER2 status, and post-NAC cN stage. It showed strong discriminative ability, with bias-corrected AUCs of 0.858 in the training cohort and 0.855 in the validation cohort. Calibration and DCA confirmed good model performance. PPV exceeded 0.90 when the nomogram-predicted probability was ≥ 0.7 in both cohorts. This nomogram demonstrated high diagnostic accuracy for predicting ypN0 and may support the selection of candidates for axillary surgery de-escalation based on post-NAC biopsy findings. Prospective validation using biopsy-confirmed pCR is warranted.

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.

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.

Objective: The prevalence of acute hepatic porphyria (AHP) in Japan is unknown. To diagnose AHP, identifying populations with a high prevalence of AHP is essential. We focused on non-specific abdominal pain (NSAP); however, the criteria for NSAP vary across studies. Therefore, this study aimed to investigate the diagnostic process of undiagnosed abdominal pain in general medicine clinical practice before proposing a definition of NSAP. In addition, we aimed to examine the potential AHP-related symptoms and implementation of AHP testing in these patients. AHP is a rare but fatal and treatable disease; hence, its early diagnosis is essential.Design: This retrospective observational study was conducted in the general medicine departments of six medical institutions in Japan over a 3-year period beginning on April 1, 2019.Participants: Patients with abdominal pain who underwent abdominal imaging examinations were included.Main outcome measures: The primary outcome was to characterize patients with undiagnosed abdominal pain. In addition, this study aimed to identify situations where physicians attempt to diagnose AHP in patients with abdominal pain.Results: Of the 1915 eligible participants, 317 (16.6%) had undiagnosed abdominal pain, and none of them were diagnosed with AHP in diagnosed abdominal pain. The median patient age was 55 years, and 134 patients were male. Multivariate logistic analysis revealed that hospitalization, dull pain, and the absence of depressive symptoms were associated with abdominal pain. All patients with undiagnosed abdominal pain demonstrated two to four indicative symptoms of AHP. However, none underwent urinalysis for a definitive diagnosis of AHP.Conclusions: Depressive symptoms and the absence of dull pain were associated with undiagnosed abdominal pain. Hospitalization for examination contributed to improving the diagnosis of abdominal pain. Despite the presence of indicative symptoms, urinary markers for AHP diagnosis were not measured. Establishing a diagnostic strategy for undiagnosed abdominal pain would provide better opportunities for patients with NSAP and could help shorten the diagnostic journey for those with rare diseases such as AHP.

Background:EGFR L858R mutation is associated with poorer efficacy of EGFR-tyrosine kinase inhibitors (TKIs) than EGFR Ex19del in patients with non-small cell lung cancer (NSCLC). However, ramucirumab (RAM) + erlotinib (ERL) therapy exhibited comparable efficacy between patients with L858R mutation and Ex19del mutation (median progression-free survival (PFS): 19.6 vs 19.4 months) in the RELAY study, with favorable PFS for both gene mutations at 19.4 months in the Japanese subset. Meanwhile, the FLAURA study revealed shorter PFS with osimertinib (OSI) for L858R mutation than Ex19del mutation, with poorer PFS in the Japanese subset than in the overall population. The treatment discontinuation rates of RAM + ERL and OSI in Japanese patients were 18% and 29%, respectively. Consequently, RAM + ERL may exhibit superior efficacy and safety in Japanese patients with the L858R mutation.Objectives:To evaluate the therapeutic efficacy and safety of RAM + ERL as a first-line treatment for advanced or recurrent NSCLC harboring the L858R mutation in Japanese patients.Design:A multicenter, noninterventional, retrospective cohort study.Methods and analysis:This study will involve patients with advanced or recurrent NSCLC (ECOG PS score 0–2) with L858R mutation who received RAM + ERL between November 1, 2020 and August 31, 2023, with the planned sample size of 200 patients. The primary endpoint is time to treatment failure, and the secondary endpoints are overall survival, PFS, PFS2, time to discontinuation of any EGFR-TKI, time to failure of strategy, objective response rate, disease control rate, and safety. Exploratory endpoints are effects of ERL and RAM on PD-L1 expression and neutrophil-to-lymphocyte ratio.Discussion:To the best of our knowledge, this is the first retrospective study focusing on L858R mutations associated with the RELAY regimen, providing the corresponding real-world data.Trial registration:UMIN Clinical Trials Registry identifier: UMIN000052047.

We aimed to determine the compliance, safety, and acceptance of colon capsule endoscopy (CCE) and small bowel capsule endoscopy (SBCE) in an out-of-clinic setting remotely supported by medical staff. We enrolled 30 examinees (24 with CCE and six with SBCE) who had not undergone CE at six gastroenterological centers. All examinees were provided with instructions on equipment and bowel preparations. CCE was performed at home (n = 16) or at the workplace (n = 8). Compliance with data-recorder alerts was 100% for bowel preparation and 79% for equipment operation. Total capsule colonoscopy was achieved in 83.3%. The overall adequate endoscopic cleansing rate was 83.3%, and abnormalities, including colorectal polyps, were detected in 37.5%. CCE malfunction, such as the inability to automatically detect the small bowel mucosa occurred in one (4.2%). One experienced mild abdominal pain that required no treatment. Inquiries were present from half of the examinees. The proportions of examinees who desired and refused CCE at the next examination were 67% and 4%, respectively. SBCE was performed at home (n = 4) or at the workplace (n = 2). Compliance with the procedures was 100%. Whole small bowel images were recorded for all examinees. The overall adequate endoscopic clearness rate was 100%. One abnormality was detected. Inquiries were present from half of the examinees. There were no adverse events or malfunctions. The proportion of examinees who reported "quite easy" and "fairly easy" was 66%. CCE and SBCE with all procedures in the out-of-clinic setting supported by remote consultations were feasible. A multicenter prospective study of the safety and acceptance of capsule endoscopy examinations at home (HomeCam-J study) (jRCTs042220163).

Introduction: Although several studies in Western countries have shown that Endocuff Vision-assisted colonoscopy (EC) can improve the colorectal adenoma detection rate (ADR), such evidence in Asia is still scarce. This study aimed to evaluate the performance of EC in detecting colorectal adenomas in Vietnamese patients. Methods: This was a randomized controlled trial conducted at a tertiary hospital in Vietnam. Subjects aged ≥18 years referred for colonoscopy for symptomatic investigation or screening were randomly assigned to the EC group or standard colonoscopy (SC) group. The primary outcome was the ADR. The secondary outcomes included the mean number of adenomas per procedure (MAP), cecal intubation time, and withdrawal time. Results: There were 476 participants (241 in the EC group, 235 in the SC group) with a median age of 52 (interquartile range [IR]: 46, 58) years. There were no significant differences between the two groups regarding age, sex, smoking status, family history of colorectal cancer, or indications for colonoscopy. Compared with the SC group, the EC group had significantly higher ADRs (35.7% vs. 22.6%, p = 0.002) and MAPs (0.68 vs. 0.39, p = 0.004). The intubation durations were comparable between the two groups. The withdrawal time in the EC group was shorter than that in the SC group (median [seconds]: 266 [IR: 224, 314] vs. 360 [IR: 310, 390], p < 0.001). Conclusions: Compared with SC, EC significantly increased both the ADR and MAP in a shorter inspection time and could be a better choice for colonoscopy screening.

PurposeTo determine prognostic parameters, we extensively examined whether physical, biochemical, and histological factors were associated with clinical outcomes in metastatic hormone sensitive prostate cancer (mHSPC) patients.MethodsA total 822 mHSPC patients were retrospectively investigated and examined the associations between prognosis and clinicopathological parameters including BMI, initial PSA level, TNM classification, Hb, Alb, CRP, AST, ALT, LDH, ALP, Gleason grade group, and EOD score.ResultsAccording to the CHAARTED criteria, 338 (41.1%) and 484 (58.9%) patients were classified into low- and high-volume disease, respectively. In univariate and multivariate analyses, Gleason grade group, Alb, CRP, LDH, and ALP were determined as significant predictors for both PFS and OS. When mHSPC patients were classified into three group including favorable (none of risk factors), intermediate (one or two risk factors) and poor (more than three risk factors) according to these four parameters, the survival curves were significantly stratified according to the risk classification. When the risk classification was applied on the patients with low- or high-volume disease in CHAARTED criteria, worse prognosis was found in poor risk group patients with low-volume disease and favorable prognosis was found in favorable risk group patients with high-volume disease.ConclusionThese results suggested that Gleason grade, CRP, LDH, and ALP were the independent predictors for mHSPC patients regardless of metastatic burden.Supplementary InformationThe online version contains supplementary material available at 10.1007/s00345-025-05862-4.