Concordance between cryobiopsy and forceps biopsy specimens in assessment of immunohistochemistry staining for non-small cell lung carcinoma.

Background: Cryobiopsy is recently being promoted for biopsy of tumors in the lung periphery in precision medicine for lung cancer; the obtained tissue samples have been reported to be more useful compared to those obtained using forceps, because of the larger volume and higher quality. However, the influence of freezing and thawing of tissues when performing cryobiopsy on the results of immunohistochemistry (IHC) has not been completely understood. Methods: In this study, consecutive patients who underwent diagnostic bronchoscopy with cryobiopsy for peripheral pulmonary lesions (PPLs) at our institution between June 2017 and November 2021 were reviewed retrospectively. Specimens of diagnosed cases of unresectable or recurrent non-small cell lung carcinoma (NSCLC) were selected. We compared the results of IHC assessment for programmed death-ligand 1 (PD-L1), human epidermal growth factor receptor 2 (HER2), and human epidermal growth factor receptor 3 (HER3) in cryobiopsy specimens versus conventional forceps biopsy specimens from the same site in the same procedure. Results: Twenty-four of 40 patients were male (60%). The most frequent histologic type of cancer was adenocarcinoma (n=31, 77.5%), followed by NSCLC (n=4, 10%), squamous cell carcinoma (n=3, 7.5%), and others (n=2, 5%). The concordance rates of the tumor proportion scores (TPSs) for PD-L1, IHC score for HER2 and, IHC scores for HER3 were 85%, 72.5%, and 75%, respectively; the weighted kappa were 0.835, 0.637, and 0.697, respectively. Conclusions: Freezing and thawing associated with cryobiopsy had virtually no effect on the results of IHC. We suggest that cryobiopsy specimens would therefore be ideal for precision medicine and translational research.

Feasibility study of cryobiopsy for practical pathological diagnosis of primary lung cancer including immunohistochemical assessment.

BACKGROUND: Precision medicine in non-small cell lung cancer requires attainment of a sufficient amount of high-quality tumor tissue. Transbronchial cryobiopsy has emerged as a new diagnostic method for non-neoplastic lung disease with a better potential to assess morphology compared with conventional methods. However, the influence of cryobiopsy on specimen quality, particularly detection of protein expression, is unknown. We performed a comparative immunohistochemical study in specimens obtained by cryobiopsy versus conventional sampling to evaluate the feasibility of cryobiopsy for lung cancer diagnosis. METHODS: Pairs of artificial biopsy specimens, collected using a cryoprobe or conventional scalpel, were obtained from 43 surgically resected primary lung tumors. Formalin-fixed, paraffin-embedded blocks were prepared in an ISO15189-certified laboratory. Immunohistochemical staining of thyroid transcription factor-1, p40, Ki67 and programmed death-ligand 1 (22C3) was performed. The H-scores for thyroid transcription factor-1 and p40, labeling index for Ki67 and tumor proportion score for programmed death-ligand 1 were assessed. Pearson's correlation coefficients between two sampling types were calculated. RESULTS: The thyroid transcription factor-1 and p40 H-scores showed perfect correlations between the cryobiopsy and conventional scalpel-obtained specimens (R2 = 0.977 and 0.996, respectively). Ki67 labeling index and PD-L1 tumor proportion score also showed strong correlations between the two sample types (R2 = 0.896 and 0.851, respectively). Five cases (11.6%) exhibited differences in tumor proportion score category between sample types, potentially because of intratumoral heterogeneity. CONCLUSIONS: Immunohistochemical expression of certain tumor markers showed a high concordance between cryobiopsy and conventional scalpel sampling. Cryobiopsy is feasible for pathological diagnostics including PD-L1 evaluation.

Assessment of factors associated with mizoribine responsiveness in children with steroid-dependent nephrotic syndrome.

BACKGROUND: Several immunosuppressants have been used to treat children with steroid-dependent nephrotic syndrome (SDNS). Mizoribine (MZR) is an immunosuppressant used to maintain remission in children with SDNS, although its effectiveness for treating SDNS remains controversial. Therefore, in this study, we assessed the clinical factors associated with children having SDNS who were successfully treated with MZR. METHODS: A total of 47 children with SDNS who underwent MZR treatment were retrospectively evaluated. Clinical features including pharmacokinetics after MZR administration were compared between MZR responders and non-responders. RESULTS: The comparison of the two groups revealed no significant differences in age, body weight (BW), daily dose of MZR per BW, serum concentration 2 h after administration (C2), peak serum concentration (Cmax), and area under the concentration curve 0-4 h after administration (AUC0-4). C2/(single dose/BW), Cmax/(single dose/BW), and AUC0-4/(single dose/BW) were significantly higher in the MZR responders than in the non-responders (all p < 0.01). Receiver operating characteristic analysis revealed that the cutoff values of C2 (single dose/kg), Cmax/(single dose/BW), and AUC0-4/(single dose/BW) were 0.55, 0.58, and 1.37, respectively. CONCLUSIONS: MZR is a useful immunosuppressant for treating frequent-relapse NS in children who are susceptible to the drug. The efficacy of MZR may be associated with not only serum concentrations defined by the dosage or absorption efficiency through MZR transporters, but also the susceptibility defined by the expression level and performance of MZR transporters on the target cells.

Primary pulmonary meningioma: A rare case report of aspiration cytological features and immunohistochemical assessment.

Ectopic meningioma is a generally rare type of benign tumor that very rarely occurs in the lung. Here, we report the cytological findings of a primary pulmonary meningioma with a particular focus on immunohistochemical (IHC) assessment. A healthy 60-year-old woman visited our hospital with an asymptomatic nodule in the right lower lung lobe. She had no particular past-history and no other tumors in the central nervous system or elsewhere according to an imaging examination. Transbronchial fine-needle aspiration cytology revealed clusters of spindle cells in a whorled formation and psammoma bodies. The tumor cells exhibited spindle-shaped cytoplasm, small fusiform or round nuclei and numerous intranuclear cytoplasmic inclusions. IHC staining of the cytological specimen revealed that the tumor cells were positive for epithelial membrane antigen, negative for thyroid transcription factor-1 and p40, and equivocal for claudin-1. Progesterone receptor immunoreactivity of cytology specimen resulted negative at first by manual method but retrieved positive by an autostainer. Following segmentectomy, the pathological diagnosis was a meningothelial meningioma. The patient has remained well without recurrence for 36 months postoperatively. Because the cytological preparation exhibited characteristic findings of meningioma, a correct diagnosis based on pre-operative cytological findings with appropriate IHC would be possible. Here, we report the cytological and IHC features of this case and highlight the importance of IHC-quality assurance.

NMR Assignment for Diaryl Ether Structures (4-O-5 Structures) in Pine Wood Lignin.

A 4-O-5-tetramer lignin model compound carrying ß-O-4 linkages on each of the side-chain moieties was synthesized, as well as 4-O-5-coupled dehydrodiconiferyl alcohol. By comparison with their NMR data, two cross-signals in the HSQC spectrum of pine milled wood lignin recorded in DMSO-d6 were assigned to H2/C2 and H6/C6 correlations on the aromatic rings of 4-O-5-linked units. Although the H2/C2 correlation peak appeared in the same region as syringyl units, nitrobenzene oxidation of the pine lignin did not yield any syringyl-type product, but did release a 4-O-5-type product.

Assessment of coronary artery disease using magnetic resonance coronary angiography: a national multicenter trial.

OBJECTIVES: This national multicenter study determined the diagnostic performance of 1.5-T whole-heart coronary magnetic resonance angiography (MRA) in patients with suspected coronary artery disease (CAD). BACKGROUND: Whole-heart coronary MRA using steady-state free precession allows noninvasive detection of CAD without the administration of contrast medium. However, the accuracy of this approach has not been determined in a multicenter trial. METHODS: Using a 1.5-T magnetic resonance imaging unit, free-breathing steady-state free precession whole-heart coronary MRA images were acquired for 138 patients with suspected CAD at 7 hospitals. The accuracy of MRA for detecting a ≥ 50% reduction in diameter was determined using X-ray coronary angiography as the reference method. RESULTS: Acquisition of whole-heart coronary MRA images was performed in 127 (92%) of 138 patients with an average imaging time of 9.5 ± 3.5 min. The areas under the receiver-operator characteristic curve from MRA images according to vessel- and patient-based analyses were 0.91 (95% confidence interval [CI]: 0.87 to 0.95) and 0.87 (95% CI: 0.81 to 0.93), respectively. The sensitivity, specificity, positive and negative predictive values, and accuracy of MRA according to a patient-based analysis were 88% (49 of 56, 95% CI: 75% to 94%), 72% (51 of 71, 95% CI: 60% to 82%), 71% (49 of 69, 95% CI: 59% to 81%), 88% (51 of 58, 95% CI: 76% to 95%), and 79% (100 of 127, 95% CI: 72% to 86%), respectively. CONCLUSIONS: Non-contrast-enhanced whole-heart coronary MRA at 1.5-T can noninvasively detect significant CAD with high sensitivity and moderate specificity. A negative predictive value of 88% indicates that whole-heart coronary MRA can rule out CAD.

Use of morphological analysis in protein name recognition.

Protein name recognition aims to detect each and every protein names appearing in a PubMed abstract. The task is not simple, as the graphic word boundary (space separator) assumed in conventional preprocessing does not necessarily coincide with the protein name boundary. Such boundary disagreement caused by tokenization ambiguity has usually been ignored in conventional preprocessing of general English. In this paper, we argue that boundary disagreement poses serious limitations in biomedical English text processing, not to mention protein name recognition. Our key idea for dealing with the boundary disagreement is to apply techniques used in Japanese morphological analysis where there are no word boundaries. Having evaluated the proposed method with GENIA corpus 3.02, we obtain F-measure of 69.01 on a strict criterion and 79.32 on a relaxed criterion. The result is comparable to other published work in protein name recognition, without resorting to manually prepared ad hoc feature engineering. Further, compared to the conventional preprocessing, the use of morphological analysis as preprocessing improves the performance of protein name recognition and reduces the execution time.