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Background and Aims: An appropriate surveillance system must be established to efficiently identify cases of intraductal papillary mucinous neoplasm (IPMN)-related malignant transformation. We analyzed the initial clinical background that affects long-term prognosis and narrowed the population for whom continued evaluation is inevitable. Methods: We included 1645 patients with IPMN treated at our hospital since 2010. We examined the types and timing of malignant transformation in terms of the worrisome features (WFs). The chi-squared test, log-rank test, and Cox proportional hazards model were used for the analysis (statistical significance at α = 0.05). Results: In total, 123 (7.5%) and 41 patients (2.5%) had IPMN-derived carcinoma (IPMN-DC) and concomitant pancreatic ductal adenocarcinoma (c-PDAC), respectively. Compared with IPMN-DC, a significantly higher proportion of c-PDAC patients were diagnosed with an advanced disease stage that developed earlier. The factors with significantly shorter time for IPMN-DC development were maximum cyst diameter (MCD) ≥ 30 mm, nonbranched type, main pancreatic duct (MPD) diameter ≥ 5 mm, and septal nodal structure (SNS) for IPMN-DC, and MCD ≥ 30 mm, main duct type, MPD ≥ 5 mm, SNS, cyst enlargement (≥2.5 mm/year), and abnormal CA19-9 levels for c-PDAC. Both groups could be significantly stratified by the number of WFs. A relative risk analysis revealed that SNS, MCD ≥ 30 mm, and MPD ≥ 5 mm were significant factors for IPMN-DC, whereas abnormal CA19-9 and SNS were significant for c-PDAC. Conversely, significantly more patients exhibiting these factors initially later developed IPMN-DC or c-PDAC. Conclusions: Ten percent of IPMN cases will develop IPMN-DC or c-PDAC, thereby requiring careful follow-up, especially in cases with SNS, abnormal CA19-9, and MCD ≥ 30 mm.

Background Methotrexate-associated lymphoproliferative disorder (MTX-LPD) is a rare but critical complication that develops in patients treated with MTX. Although MTX-LPD has been recently reported, the incidence of follicular lymphoma in the intestine is very low. Case presentation A 73-year-old woman who had been receiving MTX for over 10 years visited our hospital complaining of postprandial abdominal pain and nausea. Upper and lower digestive tract endoscopies did not show any abnormal findings. A patency capsule was stagnated at the proximal part of the ileum with a mild dilation on the oral side. An oral balloon endoscopy revealed shallow ulcerative lesions in the jejunum. She was diagnosed with MTX-LPD based on histopathological findings. The symptoms did not improve with the discontinuation of MTX, and the patient required partial resection of the small intestine. The test result for Epstein-Barr virus-encoded small RNA was negative. She was diagnosed with follicular lymphoma based on the histology findings of a surgical specimen. Postoperative positron emission tomography-computed tomography and bone marrow aspiration did not show any findings of lymphoma. On follow-up, no recurrence was noted four years after the surgery. Conclusions Herein, we report the first case of follicular lymphoma that occurred in the small intestine, negative for Epstein-Barr virus-encoded small RNA. If intestinal symptoms occur during MTX administration, it is important to directly observe by endoscopy and perform histological examination.

The prevalence of kidney stones is increasing and its recurrence rate within the first 5 years is over 50%. No treatments that prevent the occurrence/recurrence of stones have reached the clinic. Here, we show that AIM (also called CD5L) suppresses stone development and improves stone-associated physical damages. The N-terminal domain of AIM associates with calcium oxalate crystals via charge-based interaction to impede the development of stones, whereas the 2nd and C-terminal domains capture the inflammatory DAMPs to promote their phagocytic removal. Accordingly, when stones were induced by glyoxylate in mice, recombinant AIM (rAIM) injection dramatically reduced stone development. Expression of injury molecules and inflammatory cytokines in the kidney and overall renal dysfunction were abrogated by rAIM. Among various negatively charged substances, rAIM was most effective in stone prevention due to its high binding affinity to crystals. Furthermore, only AIM was effective in improving the physical complaints including bodyweight-loss through its DAMPs removal effect. We also found that tubular KIM-1 may remove developed stones. Our results could be the basis for the development of a comprehensive therapy against kidney stone disease. The circulating protein apoptosis inhibitor of macrophage (AIM) reduces kidney stone development and prevents build up, providing the basis for kidney stone disease therapy.

Background/Aims: Numerous patients with ulcerative colitis (UC) become mentally unstable after experiencing a long-standing, physically painful life, and their long-term prognosis is poorer than that of those who are mentally stable. The current study aimed to evaluate serum biomarkers for predicting mental instability, which is challenging to objectively quantify. Methods: In total, 29 refractory UC patients newly treated with filgotinib underwent measurements of blood parameters associated with depression and a quantitative assessment of quality of life using the Inflammatory Bowel Disease Questionnaire (IBDQ) before and after treatment initiation with a 12-week interval. The data collected were examined in relation to each other. Results: The induction of remission treatment with filgotinib resulted in a clinical response rate of 89.7% and a clinical remission rate of 86.2%, with all eight extraintestinal manifestations resolved. No adverse events were observed. The serum zinc, high-density lipoprotein cholesterol, mature brain-derived neurotrophic factor (BDNF) concentrations, and the IBDQ psychiatric subscores increased significantly after treatment (p < 0.05). Among these parameters, the mature-BDNF concentration and the IBDQ psychiatric subscore had the strongest positive correlation (R = 0.29, p = 0.08). Based on the logistic regression analysis, the mature-BDNF concentration (cutoff value: 20.5 ng/mL) had a sensitivity of 68.2%, specificity of 64.7%, and area under the curve of 0.67 for predicting psychiatric remission (subscore > 42.5) (p = 0.04). Conclusions: While it is not easy to objectively predict the degree of psychiatric instability in patients with refractory UC, serum mature-BDNF levels can be a useful biomarker.

Background: Esophago-tracheobronchial fistula is a severe and often fatal complication in patients with advanced esophageal cancer, requiring prompt attention. The standard treatment involves the placement of a covered stent, which is relatively simple to perform and effectively seals the fistula. However, stent migration remains a common issue, highlighting the need for improved methods to prevent it. Case Presentation: We developed an innovative double stenting method approach utilizing two types of metal stents for cases where conventional stenting led to early stent dislodgement. This technique combines the benefits of uncovered and fully covered stents while minimizing their limitations. Furthermore, it is straightforward and adaptable. In two cases treated at our facility, this method successfully maintained complete fistula coverage until the patients’ deaths, allowing them to consume food orally. Conclusions: Here, we describe the procedure in detail and discuss its significance, as our findings demonstrate the effectiveness of the double stenting technique.

We developed a surgical support system that visualises important microanatomies using artificial intelligence (AI). This study evaluated its accuracy in recognising the thoracic nerves during lung cancer surgery. Recognition models were created with deep learning using images precisely annotated for nerves. Computational evaluation was performed using the Dice index and the Jaccard index. Four general thoracic surgeons evaluated the accuracy of nerve recognition. Further, the differences in time lag, image quality and smoothness of movement between the AI system and surgical monitor were assessed. Ratings were made using a five-point scale. The computational evaluation was relatively favourable, with a Dice index of 0.56 and a Jaccard index of 0.39. The AI system was used for 10 thoracoscopic surgeries for lung cancer. The accuracy of thoracic nerve recognition was satisfactory, with a recall score of 4.5 ± 0.4 and a precision score of 4.0 ± 0.9. Though smoothness of motion (3.2 ± 0.4) differed slightly, nearly no difference in time lag (4.9 ± 0.3) and image quality (4.6 ± 0.5) between the AI system and the surgical monitor were observed. In conclusion, the AI surgical support system has a satisfactory accuracy in recognising the thoracic nerves.

Background The combination of immune checkpoint inhibitors (ICI) and platinum-based chemotherapy has rapidly become the standard first-line treatment for advanced or metastatic non-small cell lung cancer (NSCLC). However, identifying reliable predictive factors of treatment response remains a significant clinical challenge. This study comprehensively analyzed pretreatment predictive factors in patients with advanced lung cancer who received first-line ICI–chemotherapy combination therapy. Methods We retrospectively analyzed clinical data from 100 patients with advanced NSCLC who received first-line ICI–chemotherapy. Univariate and multivariate Cox proportional hazards regression analyses were used to identify prognostic factors for progression-free survival (PFS) and overall survival (OS). Univariate logistic regression analysis was used to identify factors affecting the incidence of immune-related adverse events (irAEs). Results Multivariate analysis for PFS identified Eastern Cooperative Oncology Group performance status (ECOG-PS), number of metastases, lactate dehydrogenase level, cytokeratin 19 fragment antigen level, and programmed death-ligand 1 expression as independent predictors of PFS. Multivariate analysis for OS identified ECOG-PS, number of metastases, and neutrophil-to-lymphocyte ratio as significant independent predictors of OS. Patients with liver metastases showed a significantly lower incidence of irAEs than patients without liver metastases (8.3% vs. 29.7%, P  = 0.013). The occurrence of irAEs was associated with longer PFS and OS. Conclusion This study identified pretreatment clinical and hematological factors that could predict the efficacy of ICI–chemotherapy. Furthermore, the absence of liver metastases was associated with a higher incidence of irAEs. These results underscore the critical need for individualized treatments and potential adjustment of strategies for high-risk groups to achieve a long-term durable response and better survival.

Background Occasionally, severe coronavirus disease 2019 (COVID-19) can lead to rapidly progressive interstitial lung disease (RP-ILD) by triggering or unmasking various myositis-specific autoantibodies (MSAs). Although dual positivity for anti-aminoacyl-tRNA synthetase (ARS) and anti-melanoma differentiation-associated gene 5 (MDA5) antibodies is extremely rare, its management is exceptionally complex when complicated by secondary infections. Identifying a specific anti-ARS subtype is often difficult, but clinical features such as amyopathic phenotypes and refractory lung involvement often confirm a non-Jo-1 antibody subtype, which carries a poor prognosis. Case presentation A 77-year-old female patient was admitted with COVID-19. Despite standard treatment, her respiratory condition progressively deteriorated. Initial laboratory findings revealed bicytopenia, suggesting underlying immune dysregulation. Further evaluation demonstrated dual positivity for anti-ARS and anti-MDA5 antibodies, leading to a diagnosis of RP-ILD, for which tacrolimus was initiated. During the clinical course, she developed probable COVID-19-associated pulmonary aspergillosis (CAPA). Despite multimodal therapy, including careful management of drug–drug interactions between antifungal and immunosuppressive agents, the patient experienced recurrent pneumothorax and died on day 29. Conclusions This case illustrates an extreme therapeutic challenge of managing the quadruple burden of advanced age, dual MSA positivity, severe COVID-19, and opportunistic fungal infection. Clinicians should recognize that initial bicytopenia and refractory RP-ILD in patients with severe COVID-19 may be early clinical indicators of an underlying, subclinical autoimmune state. The early identification of these features is essential for balancing intensive immunosuppression and infection control in complex cases.

BackgroundCancer-associated fibroblasts (CAFs) are essential constituents of cancer-supportive microenvironments. The high incidence of hepatocellular carcinoma (HCC) in advanced fibrosis patients implies that fibroblasts have a promoting effect on HCC development. We aimed to explore the regulators of phenotypes and function of CAFs in the liver.MethodsWe established primary cancer-associated fibroblasts (CAFs) and non-cancerous liver fibroblasts (NFs) from 15 patients who underwent HCC resection. We compared phenotypes, capacity of cytokine/chemokine production and gene expression profiles between pairs of CAFs and NFs from the same donors. We examined resected tissue from additional 50 patients with HCC for immunohistochemical analyses.ResultsThe CAFs expressed more ACTA2 and COL1A1 than the NFs, suggesting that CAFs are more activated phenotype. The CAFs produced larger amounts of IL-6, IL-8 and CCL2 than the NFs, which led to invasiveness of HuH7 in vitro. We found that Bone Morphogenetic Protein-4 (BMP4) is up-regulated in CAFs compared to NFs. The CAF phenotype and function were gained by BMP4 over-expression or recombinant BMP4 given to fibroblasts, all of which decreased with BMP4 knockdown. In tissues obtained from the patients, BMP4-positive cells are mainly observed in encapsulated fibrous lesions and HCC. Positive expression of BMP4 in HCC in resected tissues, not in fibroblasts, was associated with poorer postoperative overall survival in patients with HCC.ConclusionEndogenous and exogenous BMP4 activate liver fibroblasts to gain capacity of secreting cytokines and enhancing invasiveness of cancer cells in the liver. BMP4 is one of the regulatory factors of CAFs functioning in the microenvironment of HCC.

Idiopathic pleuroparenchymal fibroelastosis (iPPFE) is a rare interstitial lung disease characterized by upper lobe‐predominant pleural fibrosis and restrictive ventilatory impairment. However, methods for functional assessment of respiratory motion remain limited. We reported a 74‐year‐old woman who had severe restrictive impairment secondary to iPPFE, for which dynamic chest radiography (DCR) was used to evaluate respiratory mechanics. Quantitative DCR indices were compared with those of controls without pulmonary disease. DCR demonstrated markedly reduced diaphragmatic excursion, substantial decrease in respiratory lung area changes, and pronounced increase in low‐motion areas, indicating extensive regional motion restriction. These findings were consistent with impaired transmission of diaphragmatic motion due to pleural and subpleural fibrosis. This case illustrated that DCR can visualize and quantify characteristic respiratory motion abnormalities in iPPFE and may serve as a useful complementary modality to high‐resolution computed tomography and pulmonary function testing for functional assessment of iPPFE. Dynamic chest radiography (DCR) was used to evaluate respiratory mechanics in a patient with idiopathic pleuroparenchymal fibroelastosis (iPPFE) and revealed markedly reduced diaphragmatic excursion, decreased respiratory lung area change, and extensive low‐motion areas compared with controls. These findings visualized disease‐specific regional motion restriction caused by pleural and subpleural fibrosis. DCR may serve as a useful complementary modality to HRCT and pulmonary function testing for functional assessment of iPPFE.