Efficacy of osimertinib for lung squamous cell carcinoma with de novo EGFR T790M‐positive: Case report and literature review

Abstract Among epidermal growth factor receptor (EGFR) mutation‐positive non‐small cell lung cancers, squamous cell carcinoma is less common and shows lower responsiveness to first‐generation EGFR tyrosine kinase inhibitors (TKIs) compared to adenocarcinoma. However, the efficacy of osimertinib for squamous cell carcinoma with EGFR mutations is not well known. This study reports the case of a 57‐year‐old male diagnosed as having stage IIIC squamous cell lung cancer. Oncomine Dx Target Test identified EGFR exon19 deletion and de novo EGFR T790M mutation with variant allele frequencies (VAF) of 21.6% and 25.2%, respectively. The patient was treated with osimertinib after progression on chemoradiotherapy followed by durvalumab, and a partial response was maintained for more than 20 months. To predict EGFR‐TKI efficacy, confirmation of gene mutations and VAF using next‐generation sequencing is helpful

IgG4-related sclerosing cholangitis and autoimmune pancreatitis: histological assessment of biopsies from Vater's ampulla and the bile duct.

Autoimmune pancreatitis is commonly associated with immunoglobulin (Ig) G4-related sclerosing cholangitis (IgG4-SC). The discrimination between IgG4-SC and pancreatobiliary malignancies or primary sclerosing cholangitis (PSC) is now an important issue. The present study was carried out to examine the usefulness of endoscopic biopsies from Vater's ampulla and the bile duct to diagnose IgG4-SC

Clinical Significance of Serum Hemeoxygenase-1 as a New Biomarker for the Patients with Interstitial Pneumonia

Background. Serum hemeoxygenase-1 (HO-1) has been proposed to be a biomarker of lung disease activity and prognosis. The present study aimed at evaluating whether HO-1 could be a useful marker for evaluating disease activity and predicting prognosis in patients with interstitial pneumonia (IP). Materials and Methods. Serum HO-1 levels of newly diagnosed or untreated patients with IP were measured at hospitalization. We evaluated the relationships between serum HO-1 and other serum biomarkers, high resolution CT (HRCT) findings, and hospital mortality. Results. Twenty-eight patients with IP, including 14 having an acute exacerbation (AE) and 14 not having an AE, were evaluated. The patients having an AE had significantly higher HO-1 levels than those not having an AE (53.5 ng/mL vs. 24.1 ng/mL; p<0.001), and the best cut-off level to discriminate between having an AE or not having an AE was 41.6 ng/mL. Serum HO-1 levels were positively correlated with serum levels of surfactant protein-D (r=0.66, p<0.001) and the ground glass opacity score (calculated from HRCT; r=0.40, p=0.036). Patients who subsequently died in hospital had presented with significantly higher HO-1 levels than those who did not die in hospital (64.8 ng/mL vs. 32.0 ng/mL; p=0.009). Conclusion. Serum HO-1 may serve as a useful biomarker for detecting AE or predicting hospital mortality in patients with IP

Endoscopic retrograde cholangiography versus peroral cholangioscopy to evaluate intraepithelial tumor spread in biliary cancer

Background and study aims: Localized-type bile duct carcinoma (LBDC) is often accompanied by extensive intraepithelial tumor spread (ITS) ≥2 cm which makes radical resection more difficult. This retrospective case review compared the diagnostic accuracy of endoscopic retrograde cholangiography (ERC) and peroral cholangioscopy (POCS) to detect ITS beyond the visible LBDCs. Patients and methods: Forty-four consecutive LBDC patients diagnosed between April 2004 to October 2008 who underwent radical resection with histopathological analysis were included in this study. Extensive ITS was found histopathologically in one-third of the cases (32%). The outcome parameters were the presence or absence of extensive ITS and the extent of extensive ITS proximal and distal to the main tumor. Results: It was not possible to pass the cholangioscopic through the tumor sites in 6 cases. ERC correctly identified the presence of extensive ITS in 11/14 cases and did not yield any false-positive results. The three ERC-negative cases were all correctly identified by POCS plus biopsy since the cholangioscope could be passed in all three cases. The extent of extensive ITS was correctly diagnosed by ERC alone, ERC with POCS, and ERC with POCS plus mapping biopsy in 22%, 77%, and 100% of cases, respectively. Conclusions: The presence of extensive ITS could be correctly detected in 80% of cases by ERC alone. POCS with mapping biopsy provided perfect diagnostic accuracy of not only the presence/absence but also the extent of extensive ITS. However, POCS has the limitation that the cholangioscope cannot be passed through the tumor sites in approximately 15% of cases

Structure Determination of a New Juvenile Hormone from a Heteropteran Insect

The structure of the juvenile hormone (JH) in the suborder Heteroptera, order Hemiptera, has been known for a very long time to be different from the JH of other orders, but the structure has been a matter of controversy. The structure was first elucidated by an unprecedented approach involving the screening of a JH molecular library. The novel Heteroptera-specific JH (JHSB₃) is a new category of JH that is featured by the skipped bisepoxide structure

Longitudinal Analysis of Neutralizing Potency against SARS-CoV-2 in the Recovered Patients after Treatment with or without Favipiravir

The effect of treatment with favipiravir, an antiviral purine nucleoside analog, for coronavirus disease 2019 (COVID-19) on the production and duration of neutralizing antibodies for SARS-CoV-2 was explored. There were 17 age-, gender-, and body mass index-matched pairs of favipiravir treated versus control selected from a total of 99 patients recovered from moderate COVID-19. These subjects participated in the longitudinal (>6 months) analysis of (i) SARS-CoV-2 spike protein’s receptor-binding domain IgG, (ii) virus neutralization assay using authentic virus, and (iii) neutralization potency against original (WT) SARS-CoV-2 and cross-neutralization against B.1.351 (beta) variant carrying triple mutations of K417N, E484K, and N501Y. The results demonstrate that the use of favipiravir: (1) significantly accelerated the elimination of SARS-CoV-2 in the case vs. control groups (p = 0.027), (2) preserved the generation and persistence of neutralizing antibodies in the host, and (3) did not interfere the maturation of neutralizing potency of anti-SARS-CoV-2 and neutralizing breadth against SARS-CoV-2 variants. In conclusion, treatment of COVID-19 with favipiravir accelerates viral clearance and does not interfere the generation or maturation of neutralizing potency against both WT SARS-CoV-2 and its variants

Mutation profile and programmed death ligand 1 status of patients with non‐small cell lung cancer diagnosed with “adenocarcinoma” and “non‐small cell carcinoma favor adenocarcinoma”

Abstract Background The terminology for lung cancer diagnosis in small biopsies was adopted in the 2015 World Health Organization classification. If non‐small cell lung cancer (NSCLC) has no clear adenocarcinoma (AD) or squamous cell carcinoma morphology, the tumor is further classified based on mucin or immunohistochemical staining as NSCLC favor AD (NFAD), NSCLC favor squamous cell carcinoma, or NSCLC not otherwise specified. Since this new term was defined, the difference between AD and NFAD has not yet been fully explored. This study aimed to examine the differences in clinical background, gene alteration frequency, and programmed death ligand 1 (PD‐L1) expression. Methods We included patients diagnosed with AD or NFAD with small samples, and who underwent testing with the Oncomine Dx target test between August 2019 and April 2023 in Kanagawa Cancer Center. Results This study comprised 268 patients. A total of 96 patients underwent surgery after AD or NFAD diagnosis. The clinical stage was more advanced and pathological N0 was lower in NFAD than in AD. The pathology of the surgical specimens revealed that solid predominant AD was significantly more common in NFAD than in AD (p < 0.001). In both AD and NFAD, EGFR mutation was the most frequent gene alteration, followed by KRAS mutation. The frequency of EGFR mutations was significantly higher in AD than in NFAD. PD‐L1 expression was significantly higher in NFAD than in AD (p < 0.001). Conclusion This study shows a clear difference between AD and NFAD in terms of cancer progression, pathological features of the main tumor, genetic characteristics, and PD‐L1 expression

Comparison of SP263 and 22C3 pharmDx assays to test programmed death ligand‐1 (PD‐L1) expression in surgically resected non‐small cell lung cancer

Abstract Background Atezolizumab, one of the immune checkpoint inhibitors, has been approved as an adjuvant treatment following resection and platinum‐based chemotherapy in patients with stage II–IIIA non‐small cell lung cancer with 1% or more programmed death ligand‐1 (PD‐L1) expression. The Food and Drug Administration (FDA) has approved SP263 as a companion diagnostic assay for adjuvant treatment with atezolizumab; however, in clinical practice, the 22C3 assay is most commonly used for advanced non‐small cell lung cancer. Therefore, our study aimed to compare two PD‐L1 assays, SP263 and 22C3, to evaluate whether 22C3 could replace SP263 when deciding whether to administer adjuvant atezolizumab. Methods We retrospectively and prospectively analyzed 98 patients who underwent surgical resection at Kanagawa Cancer Center (Japan). An immunohistochemistry assay was performed for all the cases with both SP263 and 22C3. We statistically analyzed the concordance of PD‐L1 expression between SP263 and 22C3 assays. Results The concordance between the two assays using Cohen's kappa was κ = 0.670 (95% CI: 0.522–0.818) at the 1% cutoff and κ = 0.796 (95% CI: 0.639–0.954) at the 50% cutoff. The Spearman correlation coefficient of 0.874 (p < 0.01) indicated high concordance. PD‐L1 expression with 22C3 resulted slightly higher than that with SP263. Conclusions This study showed a high concordance of PD‐L1 expression with the SP263 and 22C3 assays. Further studies examining the therapeutic effects of adjuvant atezolizumab are required