PURPOSE: Peripheral neuropathy is common among colorectal cancer (CRC) patients who undergo oxaliplatin-based (OXL) chemotherapy. A pharmacogenetic approach can be used to identify patients at high-risk of developing severe neuropathy. This type of approach can also help clinicians determine the best treatment option and prevent severe neurotoxicity. The purpose of this study is to investigate the evidence of pharmacogenetic markers for OXL-induced peripheral neuropathy (OXIPN) in patients with CRC. METHODS: A systematic literature search was conducted using the following databases up to December 2017: Pubmed, EMBASE, and CINAHL. We reviewed the genetic risk factors for OXIPN in observational studies and randomized controlled clinical trials (RCTs). All processes were performed independently by two reviewers. RESULTS: Sixteen studies published in English between 2006 and 2017 were included in this review. A genome-wide association approach was used in one study and various candidate genes were tested, based on their functions (e.g., DNA damage or repair, ion channels, anti-oxidants, and nerve growth etc.). The genes associated with incidence or severity of OXIPN were ABCG2, GSTP1, XRCC1, TAC1, and ERCC1. CONCLUSION: This study highlighted the need and the importance of conducting pharmacogenetic studies to generate evidence of personalized OXIPN symptoms management. Additional studies are warranted to accelerate the tailored interventions used for OXIPN in patients with CRC (NRF-2014R1A1A3054386).
Colorectal Neoplasms ; DNA Damage ; Drug Therapy ; Humans ; Incidence ; Ion Channels ; Peripheral Nervous System Diseases ; Pharmacogenetics ; Risk Factors

PURPOSE: Ezrin is a membrane cytoskeletal linker protein and it is known to be associated with metastasis of primary osteosarcoma. The aim of this study is to determine the relationship between an ezrin expression and several key clinical parameters and to elucidate its potential prognostic value for patients with osteosarcoma. MATERIALS AND METHODS: Seventy patients with histologically confirmed osteosarcoma and who had no distant metastasis were enrolled between 1995 and 2005 at Yonsei Cancer Center, Severance Hospital, Korea. The clinical parameters were retrospectively reviewed and immunohistochemical staining (IHC) for ezrin was performed using the surgically resected specimens. RESULTS: Of the 70 tumor specimens, 39 (55.7%) revealed an ezrin expression. More of an osteoblastic histology and an elevated initial ALP level were observed in the ezrin positive patients than in the ezrin negative patients (p=0.008 and 0.001, respectively). The proportion of patients who favorably responded to neoadjuvant chemotherapy (> or =90% necrosis) was significantly higher in the group of ezrin positive patients than that in the group of ezrin negative patient (72.2% vs 45.2%, respectively, p=0.024). The ezrin positive patients showed more frequent recurrence than did the ezrin negative patients (64.1% vs 35.5%, respectively, p=0.017). The patients with an ezrin expression also demonstrated poorer survival than did those patients without ezrin expression (5-year EFS: 31.7% vs 61.3%, respectively, p=0.023, 5-year OS: 53.4% vs 71.0%, respectively, p=0.022). When comparing EFS according to both an ezrin expression and chemoresponsiveness, there were trends that the ezrin negative/chemoresponsive group showed the best 5-year EFS (71.4%), followed by the ezrin negative/chemoresistant group (52.9%), the ezrin positive/chemoresponsive group (38.1%) and the ezrin positive/chemoresistant group (13.6%). These trends were statistically significant (p=0.036). CONCLUSION: The expression of ezrin by IHC staining was found in 55.7% of the patients with metastasis-free osteosarcoma. Immunoreactivity to ezrin is a negative prognostic factor for survival for the patients suffering with osteosarcoma. Identifying an ezrin expression might offer a valuable piece of information when treating patients with primary osteosarcoma.
Cytoskeletal Proteins ; Humans ; Korea ; Membranes ; Neoplasm Metastasis ; Osteoblasts ; Osteosarcoma ; Recurrence ; Retrospective Studies ; Stress, Psychological

Neuroendocrine carcinoma of colon is a rare disease entity that is histologically poorly differentiated and immunochemically synaptophysin positive, enabling it to be confirmed by an immunohistochemical stain. Neuroendocrine carcinomas, in almost all cases, have poor prognosis due to a tendency of early metastasis and lack of standardized treatment. The concurrent diagnosis of neuroendocrine carcinoma and adenocarcinoma is extremely rare. The relation of these two disease entities is not understood. We experienced a patient with a colonic neuroendocrine carcinoma concurrent with adenocarcinoma. A 65-year-old male presented with abdominal pain. Emergent computed tomography suggested a malignant tumor of the ascending colon. Colonoscopy showed an infiltrative lesion in the ascending colon with a luminal narrowing, a large pedunculated lesion at the splenic flexure, and multiple small polyps in the descending colon. The patient underwent a right hemicolectomy including the pedunculated lesion. The pathology confirmed advanced neuroendocrine carcinoma in the ascending colon, adenocarcinoma in proximal descending colon, and multiple metastatic lymph nodes of neuroendocrine carcinomas on abdomen. The patient underwent the postoperative chemotherapy but did not tolerate it well and expired a year after diagnosis. We report this rare case with a review of the literature.
Abdomen ; Abdominal Pain ; Adenocarcinoma ; Carcinoma, Neuroendocrine ; Colon ; Colon, Ascending ; Colon, Descending ; Colon, Transverse ; Colonic Neoplasms ; Colonoscopy ; Humans ; Lymph Nodes ; Male ; Neoplasm Metastasis ; Phenobarbital ; Polyps ; Prognosis ; Rare Diseases ; Synaptophysin