Early diagnosis of partial interferon-γ receptor 1 deficiency prevents the development of Bacille de Calmette et Guérin osteomyelitis.

We encountered two patients with partial interferon γ receptor 1 (IFN-γR1) deficiency in whom early diagnosis enhanced disease management. Patient 1 was a 44-year-old woman with enlarged lymph nodes diagnosed in a pre-pregnancy checkup, and pathological examination revealed a Mycobacterium avium infection. Based on her history of unknown multiple osteomyelitis during early childhood, mendelian susceptibility to mycobacterial disease was suspected. Genetic analysis revealed a novel heterozygous variant in IFNGR1. Genetic counseling was administered to the patient and her husband before they had their baby. Patient 2 was a 4-month-old boy whose father was previously diagnosed with autosomal dominant IFN-γR1 deficiency owing to Bacille de Calmette et Guérin (BCG) osteomyelitis. Genetic analysis showed that he had the same INFGR1 variant. He avoided BCG vaccination and has been disease-free since then. Early diagnosis is considered to be useful for genetic counseling and essential for preventing BCG osteomyelitis.

Rapid decrease of circulating tumor DNA predicted the treatment effect of nivolumab in a lung cancer patient within only 5 days.

A 77-year-old Japanese man presented to our hospital with a 1-month history of low back pain and was diagnosed as having stage IV EGFR mutation-positive lung adenocarcinoma. After treatment with EGFR tyrosine kinase inhibitor and cytotoxic chemotherapy, nivolumab was started as fourth-line therapy. Remarkable regression of the primary tumor was observed, suggesting high anti-tumor activity of nivolumab. We retrospectively investigated the change in circulating tumor DNA (ctDNA) variant allele fractions in serial plasma samples before and after the nivolumab therapy. Targeted sequencing analysis showed tumor-derived TP53R249S and EGFRL858R mutations detectable in plasma, and the timing of decrease was only 5 days, much earlier than the appearance of radiological changes. Overall, these results suggest that ctDNA might reflect tumor burden and might be a surrogate marker of the therapeutic efficacy of immune checkpoint therapy.

Analysis of significantly mutated genes as a clinical tool for the diagnosis in a case of lung cancer.

Bronchoendoscopic examination is not necessarily comfortable procedure and limited by its sensitivity, depending on the location and size of the tumor lesion. Patients with a non-diagnostic bronchoendoscopic examination often undergo further invasive examinations. Non-invasive diagnostic tool of lung cancer is desired. A 72-year-old man had a 3.0 cm × 2.5 cm mass lesion in the segment B1 of right lung. Cytological examination of sputum, bronchial washing and curetted samples were all "negative". We could confirm a diagnosis of lung cancer after right upper lung lobe resection pathologically, and also obtained concordant results by genomic analysis using cytological negative samples from airways collected before operation. Genetic analysis showed mutational profiles of both resected specimens and samples from airways were identical. These data clearly indicated the next generation sequencing (NGS) may yield a diagnostic tool to conduct "precision medicine".