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Cancer genome profiling (CGP) occasionally identifies pathogenic germline variants (PGV) in cancer susceptibility genes (CSG) as secondary findings. Here, we analyzed the prevalence and clinical characteristics of PGVs based on nationwide real-world data from CGP tests in Japan. We analyzed the genomic information and clinical characteristics of 23,928 patients with solid cancers who underwent either tumor-only (n = 20,189) or paired tumor-normal (n = 3,739) sequencing CGP tests between June 2019 and December 2021 using the comprehensive national database. We assigned clinical significance for all variants and highlighted the prevalence and characteristics of PGVs. Our primary analysis of the tumor-normal sequencing cohort revealed that 152 patients (4.1%) harbored PGVs in 15 CSGs. Among 783 germline variants, 113 were annotated as PGVs, 70 as benign variants, and 600 as variants of uncertain significance. The number of PGVs identified was highest in BRCA1/2, with 56, followed by TP53, with 18. PGVs were the most prevalent in ovarian and peritoneal cancers, including among cancer types common in Asia. In the tumor-only sequencing cohort, of the 5,184 pathogenic somatic variants across 26 CSGs, 784 (15.1%) were extracted according to the European Society for Medical Oncology recommendations for germline-focused tumor analysis. The prevalence of PGVs was similar to that previously reported in Europe and the United States. This is the largest analysis based on real-world tumor-normal sequencing tests in Asia. The more widespread use of the tumor-normal sequencing CGP test could be reasonable for evaluating PGVs., Significance: We analyzed real-world data from over 23,000 patients in Japan, revealing 4.1% harbored PGVs, particularly in BRCA1/2 and TP53, in CSGs. It highlights the prevalence of PGVs in Asian populations and supports the broader adoption of tumor-normal sequencing CGP tests for PGV evaluation., (© 2023 The Authors; Published by the American Association for Cancer Research.)

Purpose: The present review is aimed to introduce an new occupational lung disease, Indium Lung., Methods: We searched case reports and epidemiological studies concerning indium-related lung diseases and reviewed., Results: Up to March, 2010, 7 cases of interstitial pneumonia in Japanese indium-exposed workers, two cases of pulmonary alveolar proteinosis (PAP) in US indium-exposed workers, one case of PAP in a Chinese indium-exposed worker, and 4 cross-sectional surveys in Japan had been published. All cases and epidemiological studies in Japan indicate that exposure to hardly soluble indium compounds causes interstitial as well as emphysematous lung damages, which we call "Indium Lung". Based on the epidemiological studies, the Japan Society for Occupational Health proposed 3 μg/l of indium in serum as an occupational exposure limit based on biological monitoring to prevent significant increase of KL-6., Comments: Long-term follow-up of currently and formerly indium-exposed workers is essential not only to clarify the natural history of indium lung but also to trace the incidence of lung cancer. It is also necessary to elucidate the mechanism of indium lung and difference in clinical manifestations between Japanese and US cases.

We examined graft and patient survival rates of 47,146 patients in the United Network for Organ Sharing registry following transplants between donors and recipients who were cytomegalovirus (CMV) antibody negative and positive. CMV positivity increased with age to about 80% in patients over 60. Seropositivity was seen in 80% of Asians, 71% of African Americans, and 56% of Caucasians. In all age groups, females had a slightly higher incidence of positivity than males. Transplants involving CMV-positive donors resulted in lower graft survival rates than those with CMV-negative donors. This occurred regardless of whether the recipient was CMV negative or positive. The greatest effect was on patient survival rate, which, in turn, adversely affected graft survival rate. The CMV-positive-donor effect was primarily noted in (1) Caucasian recipients, (2) patients with HLA-A,B,DR mismatches, and (3) patients older than 15 years of age. In contrast, CMV-positive donors were not a risk factor for African American and Hispanic patients, CMV-positive Asian patients, patients younger than 16 years of age, and patients with no HLA-A,B,DR antigen mismatches. In conclusion, a kidney from a CMV-positive donor is a risk factor for certain patients and currently yields about a 4% overall lower graft survival rate at 3 years than a kidney from a CMV-negative donor.

1. Approximately half of the pediatric patients received grafts from their parents and half from cadaver donors. Pediatric recipients accounted for only 5% of cadaver-donor transplants. 2. Pediatric patients differed from adults in the incidence of primary disease, principally in the occurrence of diabetes (almost no juvenile diabetics had progressed to renal failure compared with 30% among adults). Obstructive uropathy and dysplasia were the primary diseases for about 37% of pediatric patients compared with 3% in adults. 3. Pediatric patients under the age of one had a markedly lower graft survival with cadaver donors. Such patients had much higher survival rates with parental donor kidneys. 4. Pediatric retransplants from parents had a graft survival comparable to adult grafts. Regraft survival in children given cadaveric kidneys were significantly lower than adult grafts. 5. Patients under the age of 18 with no diuresis on the first day or who required dialysis in the first week had a markedly lower graft survival rate compared with that of adults with comparable early dysfunction. 6. Kidneys from donors under 2 years old yielded a 67% one-year graft survival rate in infants, but an 87% survival in patients 16-18 years of age at 6 selected individual centers. These centers, that had performed more than 20 infant-donor renal transplants, achieved results comparable to those of transplants using grafts from older donors in recipients aged over 11 years. 7. Pediatric patients who received grafts mismatched for 5- and 6-HLA antigens had a significantly lower graft survival rate than those with better matches. 8. Black patients ages 11-18 years old had a lower graft survival rate than White patients in the same age group.

1. In 1984, second graft survival rates were 10% lower than first grafts, but in 1992, the survival difference was reduced to 1%. Multiple grafts in 1984 were 23% lower than first grafts, but showed only a 7% difference in 1992. In 1992, 12% of kidney grafts were performed into second graft recipients and 3% into multiple graft recipients. 2. If first grafts survived one to 12 months posttransplant, the second graft survival was less than if they had survived longer than 12 months, as seen in many previous analyses. Here we showed that patients with a first graft duration of one to 12 months had a higher incidence of sensitization than patients with a first graft duration of more than 12 months. This may indicate that immunization was the cause of failure more frequently among those patients who rejected earlier than later. 3. Since 1989, the interval between first graft rejection and second graft transplantation was not a factor in second graft survival. A strong correlation was noted between high PRA and interval to regrafting. This probably reflects the increasing difficulty in finding negative-crossmatch donors as PRA increases. 4. Repeat mismatches for HLA-DR were deleterious to second grafts, although repeat mismatches for HLA-A,B were not, confirming earlier studies (1,5). HLA-A,B,DR mismatches correlated well with second and multiple transplant outcomes. 5. Patients receiving second cadaver-donor transplants had the same graft survival regardless of whether the first graft was another cadaver donor or a living-related one. On the other hand, second living-related donor transplants had a higher graft survival rate if the first graft had also been from a living-related rather than a cadaver donor (p < 0.05). This suggests that it would be advantageous if the first graft came from a living-related donor with a cadaver donor as the second graft, rather than the reverse situation. 6. Urine production on the first postoperative day was a very strong indicator of subsequent graft survival, particularly for second and multigraft patients. Failure to diurese on the first day resulted in a second graft survival of 60% at one year compared with 80% for those that diuresed on the first day. 7. Similarly, dialysis requirements were a major factor in predicting subsequent graft survival. For second graft patients who required dialysis, one-year graft survival was 63%, compared with 84% if no dialysis was needed. 8. The fraction of patients who had insulin dependent diabetes for first grafts was 27%, 15% for second grafts, and 9% for multiple grafts.(ABSTRACT TRUNCATED AT 400 WORDS)