Survival outcome and prognostic factors of neoadjuvant treatment followed by resection for borderline resectable pancreatic cancer.

PURPOSE: Neoadjuvant treatment may provide improved survival outcomes for patients with borderline resectable pancreatic cancer (BRPC). The purpose of this study is to evaluate the clinical outcomes of neoadjuvant treatment and to identify prognostic factors. METHODS: Forty patients who met the National Comprehensive Cancer Network definition of BRPC and received neoadjuvant treatment followed by surgery between 2007 and 2015 were evaluated. Prospectively collected clinicopathological outcomes were analyzed retrospectively. RESULTS: The mean age was 61.7 years and the male-to-female ratio was 1.8:1. Twenty-six, 3, and 11 patients received gemcitabine-based chemotherapy, 5-fluorouracil, and FOLFIRINOX, respectively. The 2-year survival rate (2YSR) was 36.6% and the median overall survival (OS) was 20 months. Of the 40 patients, 34 patients underwent resection and the 2YSR was 41.2% while the 2YSR of patients who did not undergo resection was 16.7% (P = 0.011). The 2YSR was significantly higher in patients who had partial response compared to stable disease (60.6% vs. 24.3%, P = 0.038), in patients who did than did not show a CA 19-9 response after neoadjuvant treatment (40.5% vs. 0%, P = 0.039) and in patients who did than did not receive radiotherapy (50.8% vs. 25.3%, P = 0.036). Five patients had local recurrence and 17 patients had systemic recurrence with a median disease specific survival of 15 months. CONCLUSION: Neoadjuvant treatment followed by resection is effective for BRPC. Pancreatectomy and neoadjuvant treatment response may affect survival. Effective systemic therapy is needed to improve long-term survival since systemic metastasis accounts for a high proportion of recurrence.

COQ6 Mutations in Children With Steroid-Resistant Focal Segmental Glomerulosclerosis and Sensorineural Hearing Loss.

The phenotypic combination of steroid-resistant focal segmental glomerulosclerosis (SR-FSGS) and sensorineural hearing loss has been mainly reported in patients with mitochondrial cytopathies, including primary coenzyme Q10 (CoQ10) deficiency. In this report of 10 children with SR-FSGS and sensorineural hearing loss, we found 6 patients with biallelic COQ6 mutations. Median age at the onset of nephrotic syndrome was 29 (range, 15-47) months. All patients progressed to end-stage renal disease within a median of 13 (range, 1-27) months after the onset. Kidney biopsy revealed abnormal mitochondrial proliferation in podocytes in all 6 patients. None of the 5 patients who underwent kidney transplantation developed recurrence of FSGS. Primary CoQ10 deficiency due to COQ6 mutations should be considered in children presenting with both SR-FSGS and sensorineural hearing loss. An early diagnosis of COQ6 mutations is essential because the condition is treatable when CoQ10 supplementation is started at the early stage. We recommend early kidney biopsy because detection of abnormal mitochondrial proliferation in podocytes might provide an earlier diagnostic clue.

Gene expression profiling of human hepatoblastoma using archived formalin-fixed and paraffin-embedded tissues.

We elucidated the genetic profile of hepatoblastomas (HBLs) to identify diagnostic and prognostic markers. RNA was extracted from 32 formalin-fixed, paraffin-embedded HBLs and corresponding nonneoplastic liver (NNL) tissues, and cDNA-mediated annealing, selection, extension, and ligation (DASL) chip assays were performed. Immunohistochemistry was performed to confirm the expression of Yin Yang 1 (YY1) protein in HBL. Twenty-four genes that were associated with signal transduction, cell-cell adhesion, cell cycle regulation, and apoptosis were differentially expressed in HBL and NNL tissues. Two apoptosis-associated genes, MYCN and BIRC5, were highly upregulated in HBL. Eight genes, including YY1 and IGF1, were upregulated in HBL cases that had a poor prognosis. Thirty-eight genes, including YY1, were differentially expressed according to histologic differentiation of HBL, and the immunohistochemical expression of YY1 was correlated with poor HBL differentiation. Thus, using DASL chip assays, we report the gene expression profiles of HBL, which suggest new candidate prognostic and diagnostic genetic markers and putative therapeutic targets for HBL.