Transformation and outcome of nodular lymphocyte predominant Hodgkin lymphoma : a Finnish Nationwide population-based study

Nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) is a rare B-cell malignancy associated with excellent survival. However, some patients experience histological transformation into aggressive large B-cell lymphoma. Population-based data on transformation in patients with NLPHL is limited. We conducted a nationwide population-based study to estimate the risk of transformation and relative survival in patients diagnosed with NLPHL in Finland between 1995 and 2018. We identified a total of 453 patients (median age, 48 years; 76% males) with the incident NLPHL from the Finnish Cancer Registry. The cumulative incidence of transformation was 6.3% (95% CI, 4.2-9.6) at 10 years. After adjusting for sex, age and year of diagnosis, transformation was associated with a substantially increased risk of death (HR 8.55, 95% CI 4.49-16.3). Ten-year relative survival was 94% (95% CI, 89%-100%). The patients diagnosed at a later calendar year had lower excess risk of death (HR, 0.38 per 10-year increase; 95% CI, 0.15-0.98). We conclude that while the 10-year relative survival for the patients with NLPHL was excellent in this large population-based cohort for the entire study period, transformation resulted in a substantially increased mortality compared with the patients without transformation. Our results also suggest a reduction in excess mortality over time.Peer reviewe

Cancer Incidence and Mortality in the Oldest Old: a Nationwide Study in Finland

The world's population is aging rapidly. This study reports the burden of cancer in the oldest old (≥85 years) in Finland in 1953-2017 and estimates age-specific cancer rates in the old population (65-99 years) in 1988-2017. The Finnish Cancer Registry provided data on all cancer diagnoses, cancer deaths and other deaths in cancer patients in Finland in 1953-2017. Between 1953-1957 and 2013-2017, the proportion of incident cancers in those aged ≥85 years increased from 1.5% to 9.6% (597 to 15,360 new cases), and in 2013-2017, more new cancers were diagnosed at age ≥85 years than age <50 years. Cancer incidence and excess mortality attributable to cancer peaked at age 85-94 years and declined subsequently, whereas cancer-specific mortality continued to increase or plateaued. Due to demographic changes, the number of new cancers in the oldest old has increased substantially in Finland, and currently, nearly one in 10 cancers are diagnosed in this age group. The increasing cancer burden in the oldest old poses a major challenge for healthcare and needs to be addressed in designing clinical research and reporting of cancer registries. In old populations with competing risks of death, we propose excess cancer mortality as a measure of cancer-related mortality.Peer reviewe

Transformation and outcome of nodular lymphocyte predominant Hodgkin lymphoma: a Finnish Nationwide population-based study

Nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) is a rare B-cell malignancy associated with excellent survival. However, some patients experience histological transformation into aggressive large B-cell lymphoma. Population-based data on transformation in patients with NLPHL is limited. We conducted a nationwide population-based study to estimate the risk of transformation and relative survival in patients diagnosed with NLPHL in Finland between 1995 and 2018. We identified a total of 453 patients (median age, 48 years; 76% males) with the incident NLPHL from the Finnish Cancer Registry. The cumulative incidence of transformation was 6.3% (95% CI, 4.2-9.6) at 10 years. After adjusting for sex, age and year of diagnosis, transformation was associated with a substantially increased risk of death (HR 8.55, 95% CI 4.49-16.3). Ten-year relative survival was 94% (95% CI, 89%-100%). The patients diagnosed at a later calendar year had lower excess risk of death (HR, 0.38 per 10-year increase; 95% CI, 0.15-0.98). We conclude that while the 10-year relative survival for the patients with NLPHL was excellent in this large population-based cohort for the entire study period, transformation resulted in a substantially increased mortality compared with the patients without transformation. Our results also suggest a reduction in excess mortality over time

Familial cancer risk in family members and spouses of patients with early-onset head and neck cancer

Background Reported patterns of familial aggregation of head and neck cancer (HNC) vary greatly, with many studies hampered by the limited number of subjects. Methods Altogether 923 early-onset ( Results Of all early-onset HNC families, only 21 (2.3%) had familial HNC cancers at any age and less than five familial early onset HNC cancers among first-degree relatives. The cumulative risk of HNC for siblings by age 60 (0.52%) was at population level (0.33%). No increased familial risk of early-onset HNC could be discerned in family members (SIR 2.68, 95% CI 0.32-9.68 for first-degree relatives). Conclusions Our study indicates that the cumulative and relative familial risk of early-onset HNC is modest in the Finnish population and, at most, only a minor proportion of early-onset HNCs are due solely to inherited genetic mutations.Peer reviewe

Multiple clinical characteristics separate MED12-mutation-positive and -negative uterine leiomyomas

Up to 86% of uterine leiomyomas harbour somatic mutations in mediator complex subunit 12 (MED12). These mutations have been associated with conventional histology, smaller tumour size, and larger number of tumours within the uterus. Prior studies, with limited sample sizes, have failed to detect associations between other clinical features and MED12 mutations. Here, we prospectively collected 763 uterine leiomyomas and the corresponding normal myometrial tissue from 244 hysterectomy patients, recorded tumour characteristics, collected clinical data from medical records, and screened the tissue samples for MED12 mutations to assess potential associations between clinical variables and mutation status. Out of 763 leiomyomas, 599 (79%) harboured a MED12 mutation. In the analysis of tumour characteristics, positive MED12-mutation status was significantly associated with smaller tumour size, conventional histology, and subserous location, relative to intramural. In the analysis of clinical variables, the number of MED12-mutation-positive tumours showed an inverse association with parity, and the number of mutation-negative tumours showed a positive association with a history of pelvic inflammatory disease. This study confirmed the previously reported differences and discovered novel differentiating features for MED12-mutation-positive and -negative leiomyomas. These findings emphasise the relevance of specific driver mutations in genesis and presentation of uterine leiomyomas.Peer reviewe

Genetic predisposition to uterine leiomyoma is determined by loci for genitourinary development and genome stability

Uterine leiomyomas (ULs) are benign tumors that are a major burden to women's health. A genome-wide association study on 15,453 UL cases and 392,628 controls was performed, followed by replication of the genomic risk in six cohorts. Effects of the risk alleles were evaluated in view of molecular and clinical characteristics. 22 loci displayed a genome-wide significant association. The likely predisposition genes could be grouped to two biological processes. Genes involved in genome stability were represented by TERT, TERC, OBFC1 - highlighting the role of telomere maintenance - TP53 and ATM. Genes involved in genitourinary development, WNT4, WT1, SALL1, MED12, ESR1, GREB1, FOXO1, DMRT1 and uterine stem cell marker antigen CD44, formed another strong subgroup. The combined risk contributed by the 22 loci was associated with MED12 mutation-positive tumors. The findings link genes for uterine development and genetic stability to leiomyomagenesis, and in part explain the more frequent occurrence of UL in women of African origin.Peer reviewe

ANALISIS PENERAPAN TOTAL PRODUCTIVE MAINTENANCE (TPM) DI PT CHANDRA ASRI PETROCHEMICAL TBK

PT Chandra Asri Petrochemical Tbk merupakan perusahaan terbesar dan terintegrasi di Indonesia yang menghasilkan produk biji plastik. Dalam dunia industri petrokimia, kondisi dan kinerja alat dan mesin menjadi salah satu penentu pencapaian target produksi yang ditetapkan. Kondisi mesin dan peralatan harus dijaga agar selalu dalam kondisi prima dan siap digunakan seoptimum mungkin dengan cara pemeliharaan dan perbaikan (maintenance). Dari hasil laporan data tahunan yang dimiliki perusahaan diketahui adanya permasalahan yang sering terjadi di mesin Product Discharge System pada train 2 sehingga sering terjadi breakdown. Salah satu metode yang dapat mengetahui pengaruh breakdown terhadap jumlah produksi yaitu dengan menggunakan metode Overall Equipment Effectiveness (OEE), di mana breakdown menjadi salah satu indikator yang digunakan dalam perhitungan OEE yaitu Availability. Dengan perhitungan yang ada, maka akan didapatkan hasil nilai Overall Equipment Effectiveness dan dilanjutkan dengan proses analisis six big losses untuk menentukan kerugian mana saja yang paling berpengaruh. Hasil dari penelitian yaitu didapatnya hasil rata-rata Overall Equipment Effectiveness yaitu sebesar 85,4% dengan losses terbesar ditemukan pada Equipment Failure Losses dengan persentase paling besar yaitu 47,65% dari keenam losses lainnya. Dari hasil Equipment Failure Losses ini dapat diketahui bahwa yang mempengaruhi besarnya nilai dari hasil tersebut dikarenakan angka kerusakan pada valve Product Discharge System yang cukup tinggi serta waktu untuk setup dan adjustment yang lama. Berdasarkan hasil tersebut serta konsultasi dengan pihak perusahaan, maka didapatkan beberapa solusi yang dapat diimplementasikan perusahaan untuk perbaikan ke depannya yang lebih baik

Exome and immune cell score analyses reveal great variation within synchronous primary colorectal cancers

BACKGROUND: Approximately 4% of colorectal cancer (CRC) patients have at least two simultaneous cancers in the colon. Due to the shared environment, these synchronous CRCs (SCRCs) provide a unique setting to study colorectal carcinogenesis. Understanding whether these tumours are genetically similar or distinct is essential when designing therapeutic approaches. METHODS: We performed exome sequencing of 47 primary cancers and corresponding normal samples from 23 patients. Additionally, we carried out a comprehensive mutational signature analysis to assess whether tumours had undergone similar mutational processes and the first immune cell score analysis (IS) of SCRC to analyse the interplay between immune cell invasion and mutation profile in both lesions of an individual. RESULTS: The tumour pairs shared only few mutations, favouring different mutations in known CRC genes and signalling pathways and displayed variation in their signature content. Two tumour pairs had discordant mismatch repair statuses. In majority of the pairs, IS varied between primaries. Differences were not explained by any clinicopathological variable or mutation burden. CONCLUSIONS: The study shows major diversity within SCRCs. Rather than rely on data from one tumour, our study highlights the need to evaluate both tumours of a synchronous pair for optimised targeted therapy.Peer reviewe