Accuracy of endobronchial ultrasound-guided transbronchial needle aspiration for staging of non-small cell lung cancer.

BACKGROUND: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is routinely performed to confirm a lung cancer diagnosis and/or to clinically stage disease. EBUS-TBNA findings may be used to determine whether patients can be offered potentially curative surgery. In this study, we evaluated the reporting in our service of EBUS-TBNA cytology for early-stage (operable) non-small cell lung cancer (NSCLC), focusing on diagnostic accuracy and analyzing cases with discordant cytologic and post-surgical histopathologic conclusions. METHODS: Cytology slides and cytopathology reports of 120 NSCLC patients who had undergone EBUS-TBNA and lobectomy in our hospital system between 2015 and 2021 were retrospectively reviewed. RESULTS: Of 290 lymph nodes (110 cases) able to be reviewed, interpretation of 48 lymph nodes was discordant with the original cytopathology report. This included 31 lymph nodes originally reported as adequate, which were found to be non-diagnostic on review. The diagnostic accuracy (benign/malignant) of lymph nodes that were sampled at EBUS-TBNA and excised at surgery was 89%. Specific examination of cases where EBUS-TBNA cytology did not reflect post-surgical findings illustrated important features and limitations of the procedure. These included potential misclassification of lymph node stations, the presence of multiple, variably involved nodes at lymph node stations, and the failure to detect small volume disease. CONCLUSIONS: Continuous evaluation of EBUS-TBNA performance identifies technical limitations and areas of improvement for cytopathology reporting. This is increasingly important in an era where lung cancer screening is expected to increase diagnosis of early-stage disease and with the advent of novel treatments, including non-surgical management options.

Liver Transplant for Adult Recurrent Hepatic Mesenchymal Hamartoma and a Feasible Treatment Modality: A Case Report and Literature Review.

BACKGROUND: Adult hepatic mesenchymal hamartoma (HMH) is an extremely rare hepatic tumor. Recurrence following complete resection is uncommon. Liver transplantation (LT) is described as a possible treatment option in nonresectable HMH. We conducted a systematic review investigating LT in adult HMH followed by a case report describing evidence of extensive recurrence following complete resection of large right-sided HMH requiring LT. CASE REPORT: A 46-year-old woman with symptomatic large right-hepatic HMH underwent right hemi-hepatectomy with histologic evidence of complete resection. Two and a half years postresection, she presented with abdominal pain and distension; imaging revealed large multi-septated hepatic cystic lesions within the liver suggestive of extensive recurrence of disease with concerns of malignant sarcomatous transformation. After a multidisciplinary team discussion, the lesion was deemed unresectable and the patient was referred for LT. Findings on transplantation included giant multiple hepatic cystic lesions occupying the entire abdomen and histopathological analysis confirmed recurrent HMH with no malignancy. The 6-month follow-up was unremarkable with no signs of postoperative complications or rejection. CONCLUSION: We identified only 3 reported adult unresectable HMH cases in the English literature requiring LT, with good clinical outcome and no rejection on a 1-year follow-up. To our knowledge, we report the first recurrent HMH that required LT in the English literature. Current evidence suggests possible malignant sarcomatous transformation of those lesions. No guidelines exist on postresection surveillance for HMH; however, given their malignant potential, we suggest a benefit of imaging-based surveillance following HMH resection. Offering LT for nonresectable or recurrent HMH is a feasible treatment modality with a reported good outcome.

PhOxi-Seq: Single-Nucleotide Resolution Sequencing of N2-Methylation at Guanosine in RNA by Photoredox Catalysis.

Chemical modifications regulate the fate and function of cellular RNAs. Newly developed sequencing methods have allowed a deeper understanding of the biological role of RNA modifications; however, the vast majority of post-transcriptional modifications lack a well-defined sequencing method. Here, we report a photo-oxidative sequencing (PhOxi-seq) approach for guanosine N2-methylation, a common methylation mark seen in N2-methylguanosine (m2G) and N2,N2-dimethylguanosine (m22G). Using visible light-mediated organic photoredox catalysis, m2G and m22G are chemoselectively oxidized in the presence of canonical RNA nucleosides, which results in a strong mutation signature observed during sequencing. PhOxi-seq was demonstrated on various tRNAs and rRNA to reveal N2-methylation with excellent response and markedly improved read-through at m22G sites.

Single-nucleotide resolution of N 6-adenine methylation sites in DNA and RNA by nitrite sequencing.

A single-nucleotide resolution sequencing method of N 6-adenine methylation sites in DNA and RNA is described. Using sodium nitrite under acidic conditions, chemoselective deamination of unmethylated adenines readily occurs, without competing deamination of N 6-adenine sites. The deamination of adenines results in the formation of hypoxanthine bases, which are read by polymerases and reverse transcriptases as guanine; the methylated adenine sites resist deamination and are read as adenine. The approach, when coupled with high-throughput DNA sequencing and mutational analysis, enables the identification of N 6-adenine sites in RNA and DNA within various sequence contexts.