We investigated the factors associated with the success of switching to faricimab for type 1 macular neovascularization (MNV) refractory to intravitreal aflibercept (IVA). This retrospective cohort ...study included patients with type 1 MNV who were switched to faricimab because they were refractory to IVA at two centers. The primary endpoint was a more than two-week extension of the treatment interval after 6 months. In addition, factors related to the success or failure of extension and visual and anatomical outcomes were assessed. The analysis included 43 eyes from 43 patients. Extended dosing intervals of >2 weeks were identified in 14 eyes (32.6%). A short dosing interval before switching, absence of polypoidal lesions, and thin central choroidal thickness before switching were identified as factors involved in successful extension. For patients with refractory type 1 MNV, switching to faricimab is a safe and potential option to extend existing dosing intervals.
Genomic profiling of tumors is available, but whether the small fragment obtained via endoscopic ultrasound-guided fine needle biopsy (EUS-FNB) is sufficient for these examinations is unknown. Here ...we investigated whether EUS-FNB specimens are suitable for genomic profiling to identify oncogenic and drug-matched mutations.
We constructed a pancreatobiliary cancer panel for targeted panel sequencing that covered 60 significantly mutated genes and compared the results with those of whole-exome sequencing (WES). In total, 20 and 53 formalin-fixed paraffin-embedded tissues obtained via surgery and EUS-FNB were analyzed, respectively. First, we examined the DNA quality and genomic profiles of 20 paired samples from 20 malignant lesions obtained via surgery and EUS-FNB. We then tested 33 samples obtained via EUS-FNB from 24 malignant and 9 benign lesions for the discrimination of malignancy. Finally, we explored drug-matched mutations from EUS-FNB specimens.
Although the DNA quantity obtained via surgery was higher than that obtained via EUS-FNB (P = 0.017), the DNA quality and mean depth were equivalent (P = 0.441 and P = 0.251). Panel sequencing of EUS-FNB specimens identified more oncogenic mutations than WES (90 % vs. 50 %). Furthermore, the number of oncogenic mutations did not differ between EUS-FNB and surgically resected specimens. Genomic profiling of EUS-FNB specimens enabled the discrimination of malignancy with 98 % accuracy. Of 44 malignant lesions, drug-matched alterations were identified in 14 % (6/44) of malignant lesions.
EUS-FNB specimens can be widely utilized for diagnostic purposes, discrimination of malignancy, and detection of drug-matched mutations for the treatment of pancreatic cancer.
•Genomic analysis of FFPE tissue obtained via EUS-FNB revealed oncogenic mutations in almost all patients with PC.•Genomic profiles of EUS-FNB specimens could better discriminate malignancies than conventional histological diagnosis.•Actionable mutations were detected in around 90 % of patients with PC.•EUS-FNB specimens have great potential for revealing the genomic profile of primary tumors in the era of precision medicine.
To evaluate roles of tumor-associated macrophages (TAMs) for prognosis of classical Hodgkin lymphoma (CHL). Expression of markers for TAMs, CD68, HLA-DR, CD163, HLA-DR/CD68 (M1), and CD163/CD68 (M2) ...was immunohistochemically examined in 82 cases with CHL. Positively stained cells were counted and correlation of number of TAMs and patients’ survival time was analyzed. Number of CD163+ cells and M2 cells was significantly correlated with shorter overall survival (
P
< 0.05), while it was marginally significant for CD68+ cells (
P
= 0.0827). HLA-DR + cells and M1 cells showed no significant correlation with overall survival. When confined to mixed cellularity subtype, number of M1 cells was correlated with favorable prognosis (
P
< 0.05), while M2 did not (
P
= 0.7). Older age and male sex were unfavorable factors for prognosis. At multivariate analysis, number of CD163+ cells, M2+ cells, and age were independent factors for poor overall survival (
P
= 0.03, 0.02, and 0.01, respectively). CD163+ cells and M2 cells might work to be tumor promotive in CHL. M1 cells might be tumor suppressive in mixed cellularity type.
Aim
Esophageal squamous cell carcinoma (ESCC) is a refractory digestive organ cancer that requires better treatment strategies. We have recently reported that the antidiabetic drug metformin exerts ...antitumor effects on ESCC by inhibition of nuclear factor kappa B (NF‐κB) nuclear translocation. In the present study, we focused on caspase recruitment domain family member 9 (CARD9), an essential signal adapter in NF‐κB activation to examine whether it can be used as a prognostic factor in ESCC.
Methods
We investigated CARD9 expression immunohistochemically in clinical samples obtained from 93 patients with ESCC who underwent curative esophagectomy. CARD9 expression was analyzed for correlation with clinicopathological characteristics and ESCC prognosis. The molecular effects were investigated by knocking down ESCC cells. Comprehensive RNA expression changes in these ESCC cells were detected by next‐generation sequencing (NGS).
Results
High CARD9 expression is significantly correlated with advanced tumor depth (P < .001), positive lymph node metastasis (P = .005) and advanced stage (P = .001). Kaplan‐Meier method and the log‐rank test showed that overall survival (OS) and disease‐free survival (DFS) were significantly poor in the high CARD9 expression group (OS: P = .027, DFS: P = .005). Univariate and multivariate analysis showed that high CARD9 expression is a significant poor prognostic factor for DFS. Cell proliferation and migration were suppressed by CARD9 knockdown. NGS detected altered the expression of some RNAs including maternally expressed 3 (MEG3).
Conclusion
High CARD9 expression is significantly associated with poor prognosis. Therefore, CARD9 expression may be a prospective prognostic biomarker in ESCC.
In this report, we focused on the CARD9 gene, which acts as an essential signal adapter in the mechanism of activating NF‐κB. We investigated CARD9 expression immunohistochemically in 93 patients with ESCC who underwent curative esophagectomy. High expression of CARD9 was significantly associated with a poor prognosis, and CARD9 expression may be a prospective prognostic biomarker in ESCC.
In malignant mesotheliomas, cases involving the peritoneum as the primary site are rare, accounting for approximately 10% of all mesothelioma cases. We report a case of medical-type peritoneal ...mesothelioma leading to death 2 months after the onset of fever of unknown origin, along with a review of the literature. A 76-year-old man presented with a fever of unknown origin over 4 weeks. Thoracoabdominal computed tomography (CT) scan showed increased mesenteric adipose tissue density. 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) scan showed diffuse hyperaccumulation in the mesentery and hyperaccumulation in the intraperitoneal and parasternal lymph nodes. A thoracoscopic biopsy of the parasternal lymph nodes revealed metastatic peritoneal mesothelioma. The treatment plan was discussed with him and his family, and the best supportive care was provided. 2 months later, he died from multiple organ failure. Underlying malignant tumors cause 38% of mesenteric panniculitis cases. Symptoms accompanied by lymphadenopathy within the area of mesenteric panniculitis are highly suggestive of malignancy. Peritoneal mesothelioma can be classified as (1) classical, which is accompanied by abdominal pain, ascites, and abdominal masses; (2) surgical, which is accompanied by hernia incarceration and intestinal occlusion; and (3) medical, wherein systemic symptoms, such as fever and weight loss, are primarily observed. The medical-type peritoneal mesothelioma, wherein systemic symptoms are primarily observed, has a poorer prognosis than the other types. FDG-PET/CT is an effective diagnostic modality for peritoneal mesothelioma and typically shows diffuse hyperaccumulation along the peritoneal surface.
Background
Diagnosing biliary tract cancer is difficult because endoscopic retrograde cholangiopancreatography (ERCP) is performed fluoroscopically, and the sensitivity of bile cytology is low. ...Liquid biopsy of bile using targeted sequencing is expected to improve diagnosis and treatment, but few studies have been conducted. In this study, we examined whether liquid biopsy of bile improves the diagnostic sensitivity of biliary strictures.
Methods
A total of 72 patients with biliary strictures who underwent ERCP at Chiba University Hospital between April 2018 and March 2021 were examined. Of these, 43 and 29 were clinically and pathologically diagnosed as having malignant and benign biliary strictures, respectively. We performed targeted sequencing of bile obtained from these patients, and the sensitivity of this method was compared with that of bile cytology. Detection of at least one oncogenic mutation was defined as having malignancy.
Results
The sensitivity of bile cytology was 27.9%, whereas that of genomic analysis was 46.5%. Comparing bile cytology alone with the combination of cytology and genomic analysis, the latter was more sensitive (53.5%, p < .001). Among the 43 patients with malignant biliary strictures, mutations with FDA‐approved drugs were detected in 11 (26%).
Conclusions
Liquid biopsy of bile can potentially diagnose malignancy and detect therapeutic targets.
Miura and colleagues demonstrated that liquid biopsy of bile is useful for the diagnosis of malignant lesions and the detection of therapeutic targets, and that this method has the potential to diagnose malignant lesions at an early stage.
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