Shinko Hospital

We evaluated the prognostic significance and implications of a major pathologic response (MPR) after preoperative treatment for pancreatic ductal adenocarcinoma (PDAC). Preoperative treatment is increasingly used for PDAC to improve oncologic outcomes. The pathologic response represents a potential indicator of treatment efficacy; however, its prognostic value in PDAC remains unclear. We retrospectively analyzed 739 patients who underwent pancreatectomy for PDAC after preoperative treatment at 21 institutions in Japan. The pathologic response was graded using Evans' classification, with MPR defined as Evans grade III/IV. Survival outcomes and prognostic factors were evaluated, and factors associated with achieving MPR were analyzed to develop a predictive model. MPR was achieved in 11.5% of patients. The MPR group had a significantly longer median overall survival (71.5 vs. 40.9mo) and recurrence-free survival (55.5 vs. 15.2mo) than the non-MPR group. Multivariate analysis identified MPR as an independent prognostic factor for overall survival. In the MPR subgroup, neither overall nor recurrence-free survival differed according to adjuvant chemotherapy administration; multivariate analysis did not identify adjuvant therapy as an independent prognostic factor. Predictive factors for achieving MPR included chemoradiotherapy, preoperative duration ≥6 months, normal carbohydrate antigen 19-9 after preoperative treatment, and complete or partial radiologic response. Finally, we developed a simplified predictive model for achieving MPR. MPR was independently associated with favorable survival in PDAC. The prognostic impact of adjuvant chemotherapy was not observed among patients who achieved MPR, suggesting that MPR may inform individualized postoperative management and warrants prospective validation.

Treprostinil has been approved for pulmonary hypertension associated with interstitial lung disease (PH-ILD) in Japan. This report aimed to evaluate long-term effects of inhaled treprostinil in Japanese patients with PH-ILD based on observation over 52 weeks. Inhaled treprostinil was administered via a nebulizer from 18μg (three breaths, four times daily) to 72μg (12 breaths, four times daily) at minimum 3-day intervals. World Health Organization (WHO) functional class, clinical worsening, adverse events, pulmonary function and ILD-related biomarkers were evaluated throughout the trial. Among 20 patients, 16 and 13 completed the 52-week and 100-week observation periods, respectively. Eleven patients continued on the trial until transitioning to a commercially available product. The reasons of discontinuation in nine patients were adverse events in six patients (including four adverse drug reactions (ADRs)), withdrawal of consent in two patients, and lung transplantation in one patient. The median observation period was 107.5 weeks (interquartile range, 61.4-128.8 weeks) in 20 patients. Among 13 patients observed until week 100, WHO functional class was maintained in 69.2% (9/13), and improved from class III to class II in 30.8% (4/13). The main ADRs included cough, malaise, and blood pressure decreased. At the final measurement timepoint in each patient, 70.0% (14/20) and 83.3% (15/18) maintained had no absolute decline of forced vital capacity ≥5% and diffusing capacity for carbon monoxide ≥10%, respectively. Considering its long-term clinical benefits and tolerability, inhaled treprostinil is a promising treatment option for patients with PH-ILD. Japan Registry of Clinical Trials (jRCT), jRCT2051210016. (first registered: May 7, 2021).

Symptomatic ulnar nerve (UN) dislocation is an under-recognized cause of medial elbow pain in overhead athletes. Traditionally, surgery has been considered when symptoms persist; however, advances in dynamic ultrasound (US) and US-guided targeted interventions may enable conservative treatment. Reports on long-term return to play (RTP) after US-guided physiotherapy remain scarce.A 20-year-old right-handed collegiate sidearm pitcher developed progressive medial elbow pain for one year, with acute worsening two weeks before presentation. Clinical examination suggested ulnar collateral ligament (UCL) strain and concomitant neurogenic thoracic outlet syndrome (N-TOS). Dynamic US revealed an anterior UN dislocation over the medial epicondyle during elbow flexion, which reproduced the patient’s pain.Management was performed using a stepwise strategy. Phase 1 targeted the proximal contributors (N-TOS) using scapular and chin retraction exercises combined with neural mobilization. Phase 2 addressed the primary distal pathology with US-guided perineural soft tissue mobilization, and skin-pinch traction was applied until movement of the myofascial trilaminar retinaculum (MTR) was confirmed under US, thereby improving the perineural tissue. This was followed by pain-free UN-sliding exercises.After 12 weeks, neural tension signs subsided, and pain during dynamic UN displacement diminished. A graded throwing program was completed, enabling RTP at five months. At the two-year follow-up, the athlete remained asymptomatic without recurrence, despite persistent painless dynamic subluxation on US.In this single-case report of an athlete with UN dislocation complicated by N-TOS, a stepwise, ultrasound-guided, target-specific physiotherapy approach is presented as a hypothesis-generating example of conservative management. The intervention, which included direct mobilization of the myofascial trilaminar retinaculum, facilitated a safe return to play, and no surgical intervention was required during the treatment course. In this case, ultrasound was used provisionally to monitor clinically relevant changes, such as visible improvement in neural gliding and reduction of perineural soft tissue irritation. Rather than serving as a generalized recommendation, these observations suggest a potential rationale for incorporating ultrasound into conservative management pathways.

<bold>Background and Aim:</bold> The role of airway mucus plugging in asthma pathophysiology is well-established. However, its relationship with infectious episodes and type 2 inflammation remains unclear in refractory asthma with bronchiectasis. As part of the BEXAS study (Nomura N, et al. <italic>Respir Res</italic> 2022; 23: 365), this study aimed to clarify the association between mucus plugging, infectious episodes, and type 2 inflammation, with a specific focus on plug location. <bold>Methods:</bold> Patients with refractory asthma complicated by bronchiectasis, but not with allergic bronchopulmonary aspergillosis, were included, if they had high-resolution CT images suitable for mucus score evaluation. Mucus plugging was scored separately for bilateral upper and lower lobes, as well as for the total lung. Cluster analysis was performed using mucus scores in the upper and lower lobes and the number of lobes affected by bronchiolitis. <bold>Results:</bold> Forty-two patients were included, and three distinct clusters were identified. CL 1 (n = 14) was characterized by lower-lobe-dominant mucus plugs, the highest number of bronchiolitis-affected lobes, frequent detection of Pseudomonas, systemic corticosteroid-requiring exacerbations, and bronchopneumonia. This cluster also exhibited the lowest FeNO and %FEV1. CL 2 (n = 6) showed high mucus scores in both lower and upper lobes, along with the highest FeNO levels. CL 3 (n = 22) had the lowest mucus scores overall. The degree of bronchiectasis was comparable among the three clusters. <bold>Conclusions:</bold> Lower-lobe-dominant mucus plugs may reflect the severest phenotype, characterized by frequent bronchiolitis involvement and infectious episodes. The location of mucus plugs may be clinically important.

34 participating institutions'.

背景．肺扁平上皮癌の膀胱転移は稀である．症例．76歳 男性．右肺門部扁平上皮癌 cT3N2M1c cStage IVB（右肺上葉肺内転移，右胸膜播種，癌性リンパ管症，両側腎周囲腔転移，脾転移，多発肝転移，胃転移）と診断し，1st lineとしてカルボプラチン＋ナブパクリタキセルを1コース投与した．その後小腸転移で再発し，2nd lineとしてS-1を投与しpartial responseを維持していた．投与8ヶ月後に小腸転移増大による小腸狭窄で手術を施行した．術後より突然の血尿が出現し，急激に腎後性腎不全を発症し，両側尿管開口部への腫瘍浸潤を認めた．総合的に肺扁平上皮癌の膀胱転移と診断した．血尿出現15日前にあたる入院時CTで左尿管の軽度拡張を認めていた．結論．肺扁平上皮癌の稀少な膀胱転移を経験した．肺扁平上皮癌が膀胱転移を起こし得ること及び軽度の尿管拡張が転移性膀胱腫瘍の早期所見となり得ることを知っておく必要がある．

Cerebral angiography remains the gold standard investigation for cerebrovascular disease. Transradial access is increasingly preferred over the transfemoral approach because it facilitates early ambulation and reduces complications at the access site. We report a woman in her 70s who developed delayed peripheral circulatory failure in the digital arteries following transradial cerebral angiography. After inserting a 4-French sheath into the conventional right radial artery, the catheter was advanced toward the subclavian artery but inadvertently entered a small accessory brachial artery with significant resistance, provoking severe vasospasm. The procedure was completed without incident after redirecting the catheter into the main brachial artery. Symptoms gradually appeared 24 hours after the procedure, and after 48 hours, the patient experienced burning pain, weakness, and pallor in her right hand. Angiography via the brachial artery demonstrated diffuse spasm of the radial artery, palmar arch, and digital arteries. Intra-arterial nitroglycerin quickly restored flow and alleviated symptoms. This case illustrates that inadvertent cannulation of an accessory brachial artery during transradial access can lead to delayed digital circulatory failure and that early intra-arterial vasodilator therapy is effective. Careful observation is necessary if such a catheter deviates into a small vessel with an anatomical anomaly, and spasm occurs.

A 39-year-old woman undergoing breast cancer treatment presented with a loss of appetite and fatigue. Computed tomography (CT) revealed diffuse heterogeneity in the left hepatic lobe and thickened bile duct walls with contrast enhancement. Diffusion-weighted magnetic resonance imaging (MRI) demonstrated a high signal intensity throughout the left hepatic lobe, extending to the common bile duct. The case findings highlight the extreme rarity of diffuse hepatic metastases with common bile duct infiltration in breast cancer and underscore the critical roles of CT and MRI in identifying distinctive imaging findings that are pivotal for making a diagnosis and selecting timely management.

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.

Introduction: We report an exceedingly rare case of hepatocellular carcinoma (HCC) associated with an idiopathic congenital forearm arteriovenous fistula (AVF). Given the absence of previous reports addressing the treatment of HCC in patients with AVF, we evaluate HCC treatment strategies, including the appropriateness of using angiogenesis inhibitors. Case Presentation: A 74-year-old man was admitted for the evaluation of liver tumors. His medical history included a chronic, intractable idiopathic right forearm AVF, for which he had undergone multiple surgical interventions. Abdominal EOB-MRI revealed multiple small focal lesions across both liver lobes during the hepatobiliary phase, indicative of multiple HCC, and liver biopsy confirmed early-stage HCC. Considering the potential presence of additional vascular anomalies similar to the forearm AVF, local hepatic artery chemoembolization was performed. Since there is still insufficient discussion about the systemic administration of angiogenesis inhibitors to patients with vascular abnormalities such as AVF, we discuss the treatment options for HCC with AVF, including its strategies in the progressed HCC stage. Conclusion: As molecularly targeted therapies continue to evolve, recognizing the unique aspects of cases like ours is crucial. Establishing an appropriate treatment strategy for HCC patients with AVF is imperative, highlighting the need for tailored therapeutic approaches based on individual vascular profiles.