The Predictive Value of Preoperative Health-Related Quality-of-Life Scores on Postoperative Patient-Reported Outcome Scores in Lumbar Spine Surgery.

STUDY DESIGN: A single-center, retrospective cohort study. OBJECTIVE: To predict patient-reported outcomes (PROs) using preoperative health-related quality-of-life (HRQoL) scores by quantifying the correlation between them, so as to aid selection of surgical candidates and preoperative counselling. METHODS: All patients who underwent single-level elective lumbar spine surgery over a 2-year period were divided into 3 diagnosis groups: spondylolisthesis, spinal stenosis, and disc herniation. Patient characteristics and health scores (Oswestry Low Back Pain and Disability Index [ODI], EQ-5D, and Short Form-36 version 2 [SF-36v2]) were collected at 6 and 24 months and compared between the 3 diagnosis groups. Multivariate modelling was performed to investigate the predictive value of each parameter, particularly preoperative ODI and EQ-5D, on postoperative ODI and EQ-5D scores for all the patients. RESULTS: ODI and EQ-5D at 6 and 24 months improved significantly for all patients, especially in the disc herniation group, compared to the baseline. The magnitude of improvement in ODI and EQ-5D was predictable using preoperative ODI, EQ-5D, and SF-36v2 Mental Component Score. At 6 months, 1-point baseline ODI predicts for 0.7-point increase in changed ODI, and a 0.01-point increase in baseline EQ-5D predicts for 0.01-point decrease in changed EQ-5D score. At 24 months, 1-point baseline ODI predicts for 1-point increase in changed ODI, and a 0.01-point increase in baseline EQ-5D predicts for 0.009-point decrease in changed EQ-5D. A younger age is shown to be a positive predictor of ODI at 24 months. CONCLUSIONS: Poorer baseline health scores predict greater improvement in postoperative PROs at 6 and 24 months after the surgery. HRQoL scores can be used to decide on surgery and in preoperative counselling.

Primary mucinous adenocarcinoma of the epididymis: report of a rare case with molecular genetic characterization including mutation analysis of the TP53 gene.

We report a case of primary epididymal mucinous adenocarcinoma in a 60-year-old man who presented with a scrotal mass and subsequently developed pulmonary metastases. On immunohistochemistry the tumor was positive for villin and CK20 and negative for CK7, CDX2, and thyroid transcription factor-1. Molecular genetic analysis revealed an uncommon mutation; 249: AGG →ATG in the TP53 gene, which has not been previously described in association with a primary epididymal adenocarcinoma. Mutational analysis showed KRAS, BRAF, and VHL to be wild-type. No microsatellite instability was found.

Whole-genome reconstruction and mutational signatures in gastric cancer.

BACKGROUND: Gastric cancer is the second highest cause of global cancer mortality. To explore the complete repertoire of somatic alterations in gastric cancer, we combined massively parallel short read and DNA paired-end tag sequencing to present the first whole-genome analysis of two gastric adenocarcinomas, one with chromosomal instability and the other with microsatellite instability. RESULTS: Integrative analysis and de novo assemblies revealed the architecture of a wild-type KRAS amplification, a common driver event in gastric cancer. We discovered three distinct mutational signatures in gastric cancer--against a genome-wide backdrop of oxidative and microsatellite instability-related mutational signatures, we identified the first exome-specific mutational signature. Further characterization of the impact of these signatures by combining sequencing data from 40 complete gastric cancer exomes and targeted screening of an additional 94 independent gastric tumors uncovered ACVR2A, RPL22 and LMAN1 as recurrently mutated genes in microsatellite instability-positive gastric cancer and PAPPA as a recurrently mutated gene in TP53 wild-type gastric cancer. CONCLUSIONS: These results highlight how whole-genome cancer sequencing can uncover information relevant to tissue-specific carcinogenesis that would otherwise be missed from exome-sequencing data.

Exome sequencing of gastric adenocarcinoma identifies recurrent somatic mutations in cell adhesion and chromatin remodeling genes.

Gastric cancer is a major cause of global cancer mortality. We surveyed the spectrum of somatic alterations in gastric cancer by sequencing the exomes of 15 gastric adenocarcinomas and their matched normal DNAs. Frequently mutated genes in the adenocarcinomas included TP53 (11/15 tumors), PIK3CA (3/15) and ARID1A (3/15). Cell adhesion was the most enriched biological pathway among the frequently mutated genes. A prevalence screening confirmed mutations in FAT4, a cadherin family gene, in 5% of gastric cancers (6/110) and FAT4 genomic deletions in 4% (3/83) of gastric tumors. Frequent mutations in chromatin remodeling genes (ARID1A, MLL3 and MLL) also occurred in 47% of the gastric cancers. We detected ARID1A mutations in 8% of tumors (9/110), which were associated with concurrent PIK3CA mutations and microsatellite instability. In functional assays, we observed both FAT4 and ARID1A to exert tumor-suppressor activity. Somatic inactivation of FAT4 and ARID1A may thus be key tumorigenic events in a subset of gastric cancers.