Aberrant DNA hypermethylation-silenced SOX21-AS1 gene expression and its clinical importance in oral cancer.

BACKGROUND: Long noncoding RNAs (lncRNAs) are more than 200 nucleotides in length and lack transcriptional ability. The biological function of lncRNAs in oral squamous cell carcinoma (OSCC) remains unclear. The aim of this study was to identify the dysfunction of lncRNA in OSCC. RESULTS: We analyzed the transcriptome profiles of human OSCC tissues and paired adjacent normal tissues from two patients through a next-generation sequencing approach. A total of 14 lncRNAs were upregulated (fold change ≥3) and 13 were downregulated (fold change ≤-3) in OSCC tissues compared with the adjacent normal tissues. SOX21-AS1 was subjected to further analysis, revealing that the expression levels of SOX21-AS1 significantly decreased in OSCC compared with the adjacent normal tissue. The promoter activity of SOX21-AS1 was obviously suppressed by in vitro methylation. The DNA methylation status of the SOX21-AS1 promoter was analyzed using combined bisulfite restriction analysis, revealing that the aberrant promoter hypermethylation of SOX21-AS1 was observed frequently in OSCC tissues. The effects of SOX21-AS1 on cell proliferation and invasion were examined through transient transfection. Our data showed that SOX21-AS1 could significantly suppress oral cancer cell growth and invasion. Furthermore, the low expression level of SOX21-AS1 was significantly correlated with an advanced stage (P = 0.047), large tumor size (P = 0.033), and poor disease-specific survival in OSCC patients (P = 0.002). CONCLUSIONS: SOX21-AS1 was identified as susceptible dysfunction correlated with promoter hypermethylation in OSCC. Low SOX21-AS1 expression may be an adverse prognostic biomarker for OSCC.

A high IL-4 production diplotype is associated with an increased risk but better prognosis of oral and pharyngeal carcinomas.

OBJECTIVE: Interleukin (IL)-4 is a key cytokine in humoral and adaptive immunity. This study aimed to evaluate the association of IL-4 genetic variants (-590C>T and VNTR in intron 3) with the risk and prognosis of oral and pharyngeal squamous cell carcinoma (OPSCC). DESIGN: A total of 1215 subjects, which included 623 healthy controls and 592 OPSCC cases (463 oral squamous cell carcinoma (OSCC) and 129 pharyngeal squamous cell carcinoma (PSCC) cases), were recruited. The genotypes were determined by TaqMan real-time assay and PCR-based assay. RESULTS: The IL-4 genotypes at locus -590C>T and intron 3 VNTR were not correlated with increased risk of OSCC, PSCC, and OPSCC, with the exception of early-stage OPSCC (at -590C>T: T/T vs. C/C+C/T, adjusted odds ratio (AOR)=1.42, 95% CI: 1.02-1.98; at intron 3 VNTR: RP1/RP1 vs. RP2/RP2+RP2/RP1, AOR=1.46, 95% CI: 1.05-2.04). Compared with other IL-4 diplotypes, the T,RP1/T,RP1 diplotype was associated with an increased risk of OPSCC (AOR=1.37, 95% CI: 1.03-1.81), particularly early-stage OSCC (AOR=1.43, 95% CI: 1.02-2.00), PSCC (AOR=2.35, 95% CI: 1.06-5.19), and OPSCC (AOR=1.52, 95% CI: 1.10-2.11). Interactions between the IL-4 diplotype and the alcohol drinking status were found to contribute to the risk of early-stage OPSCC (p=0.024). In addition, the T,RP1/T,RP1 diplotype was correlated with better disease-specific survival (T,RP1/T,RP1 vs. other diplotypes, adjusted hazard ratio=0.70, 95% CI: 0.50-0.97). CONCLUSION: The T, RP1/T, RP1 diplotype of IL-4 was associated with an increased risk but favourable prognosis of OPSCC.

Physicians' knowledge about pharmacological management of cancer pain--with special reference on their prescribing responses to simulated patients with cancer pain.

BACKGROUND: Cancer pain control is unsatisfactory in Taiwan. Insufficient knowledge about cancer pain on the part of physicians is an important factor responsible for ineffective cancer pain relief. Therefore, this study was to explore the knowledge deficits of physicians on the specific aspects of pharmacological management of cancer pain (PMCP) and their influences on the prescriptions to simulated patients in a southern medical center in Taiwan. METHODS: A set of self-designed questions was delivered to 234 licensed physicians with the responsibility to care for cancer patients and 111 (47.4%) questionnaires were completed and returned anonymously. RESULTS: Most of the physicians showed inadequate knowledge of the pharmacological management of cancer pain (3.34 +/- 0.49; range 1-5), which included the principle subscale (3.38 +/- 0.67) and the practice subscale (3.32 +/- 0.46). Crucial knowledge deficits of principle were identified in the preferential analgesic route and schedule. The severe practice knowledge deficits were on the meperidine, transdermal fentanyl, equianalgesic dose-conversion as well as analgesics for different pain types. Furthermore, physicians' knowledge deficits in the practice subscale, but not the principle subscale, correlated with their correct prescription of opioids to the simulated hepatoma cases. The correlates of physicians' PMCP knowledge deficits were: clinical specialty of medicine or surgery, less than 5 years or more than 10 years from medical school graduation, with limited volume of cancer pain patients being cared, and with personal unusual pain. CONCLUSIONS: The PMCP knowledge deficits were prevalent in physicians and thus influenced their prescription of opioids for the simulated cases. An active continuing education program on both the international guidelines and the essential practice skills should be implemented and intensified specifically upon subgroup physicians, to correct their misconceptions and consolidate their PMCP knowledge.

Bolus injection of adenosine before cardioplegic induction improves postischemic global function in coronary artery bypass grafting.

BACKGROUND: Alternative strategies to optimize preexisting cardioplegia during myocardial preservation are currently under extensive investigation. Adenosine, an endogenous purine nucleoside, has been approved for its cardioprotective potential against ischemic-reperfusion injury. Yet, little information is available with respect to the use of adenosine for cardioplegic induction in humans. The purpose of the present study was, therefore, to assess the clinical relevance of intra-aortic administration of adenosine following aortic cross-clamping with respect to the exertion of additional protection in routine coronary artery bypass surgery. METHODS: Thirty patients to receive elective coronary artery bypass grafting under cardiopulmonary bypass (CPB) were prospectively randomized into two study groups. Immediate after aortic cross-clamping and just before the application of modified St. Thomas cardioplegic (20 mL/kg), adenosine solution (250 microg/kg) was injected into the aortic root in the study group (n = 15), while the same amount of normal saline injection was administered in the control group (n = 15). Anesthesia was carried out in all patients in a similar fashion, and all the surgeries were performed by the same team. Homodynamic change, cardiac enzyme assay, and post-bypass inotropic supplementation were recorded throughout the study period to evaluate the extent of myocardial ischemic injury. RESULTS: The mean time to asystole after aortic cross-clamping was significantly shorter for the adenosine group compared with the control group (8.1 +/- 5.9 vs. 79.0 +/- 35.3 sec, respectively; P< 0.01). To compare with the baseline value, the mean cardiac index immediately post CPB and 24 hours postoperatively was increased significantly for the adenosine group (from 2.1 +/- 0.6 to 2.6 +/- 0.6 and 3.2 +/- 0.6 L/min/m2, respectively; P < 0.05), as contrasted with the control group (from 2.3 +/- 0.5 to 2.0 +/- 0.4 and 2.5 +/- 0.4 L/min/m2). Further, the requirement for inotropic support after CPB and postoperative troponin I release were significantly less in the adenosine group. There appeared no adverse effects associated with adenosine administration. CONCLUSIONS: Immediate administration of 250 microg/kg adenosine via the aortic root following aortic cross-clamping could optimize the myocardial protective effect of conventional cardioplegia, quicken cardiac standstill, and offer better postoperative myocardial performance after CPB.

Effects of a continuing education program on nurses' practices of cancer pain assessment and their acceptance of patients' pain reports.

A hospital-based quasi-experimental (pretest and post-test) study was conducted in Kaohsiung Veteran General Hospital, Taiwan. This study was to evaluate a continuing education program (CEP) on nurses' practices of cancer pain assessment and their acceptance of patients' pain reports with respect to four types of misconceptions. A questionnaire was sent to on-duty nurses or head nurses with patient care responsibilities before the implementation of CEP (n=645) and six months after the program (n=630). The response rates were 92.6% and 91.3% for pretest and post-test surveys, respectively. The CEP was implemented in 8 weeks with four-repeated sessions of 4-hour lectures. A one-day workshop focused on cancer pain assessment and treatment was held 3 months after the four-repeated sessions. Several educational strategies and teaching materials were used in the CEP. The results showed that CEP made statistically significant yet moderate improvement in nurses' practices of pain assessment using pain rating scales (pretest 3.29+/-0.76 vs. post-test 3.48+/-0.75, P<0.001) and acceptance of patient's pain reports without misconceptions on addiction (3.12+/-0.80 vs. 3.39+/-0.90, P<0.001), phantom pain (3.91+/-0.96 vs. 4.07+/-0.92, P=0.005), and placebo testing (3.63+/-0.72 vs. 3.81+/-0.73, P<0.001), except on patient gender-age-related doubts (3.60+/-0.72 vs. 3.67+/-0.77, P=0.109). In order to achieve further improvement, additional follow-up CEP combined with a hospital-wide institutionalization of pain assessment should be promoted and implemented in the future.

The effect of education and clinical practice on knowledge enlightenment to and attitudes toward the use of analgesics for cancer pain among physicians and medical students.

BACKGROUND: Insufficient education and limited clinical practice on the part of physicians may contribute to the undertreatment of cancer pain in Taiwan. To address these concerns, a survey among physicians and fifth-year medical students relevant to cancer pain management (CPM) was carried out in a medical school and its principal teaching hospital. METHODS: A questionnaire on CPM was sent to 97 physicians and 78 fifth-year medical students (equivalent to the third-year medical students in the United States). The same questionnaire was delivered again to these 78 fifth-year medical students after they had completed a modified curriculum of anesthesiology with a 4-hour course on introduction to clinical pharmacology of CPM. RESULTS: The physicians knowledgeable on pain (physicians of anesthesiology, hematology-oncology, or radiation oncology), physicians unfamiliar with pain (outside of anesthesiology, hematology-oncology, or radiation oncology), and the 5th-yr medical students took similar negative attitudes (24-92%, 33-89%, and 23-94%) toward the optimal use of analgesics for CPM. As compared, the mean score on knowledge of prescribing opioids of pain-knowledgeable physicians was 3.60, the highest of all as against 2.61 of other physicians and 2.54 of 5th-yr medical students. On attitudes toward prescribing opioids, both pain-knowledgeable physicians and other physicians scored a higher means, respectively of 3.52 and 2.91 as opposed to 2.68 of 5th-yr medical students, the lowest of all. However, seniority or length of clinical practice did not improve knowledge or affect attitudes toward CPM. In addition, this 4-hour course did enable the 5th-yr medical students to take a more positive attitude toward and become more knowledgeable on CPM than pain-knowledgeable physicians, as a comparison was made. CONCLUSIONS: The effect of accumulation of clinical experience and seniority of clinical practice on CPM was limited among general physicians, except for clinical specialty on anesthesiology, hematology-oncology, or radiation oncology. In Taiwan, the knowledge of and positive attitude toward CPM could only be conveyed to physicians through undergraduate, post graduate or on-job education.

A two-center survey of cardiac events and peri-operative managements of cardiac patients undergoing non-cardiac surgery in Taiwanese population.

BACKGROUND: The risk of cardiac patients undergoing noncardiac surgery is relatively high. Successful preoperative evaluation and perioperative anesthetic management of a patient require a good communication among the patient, the anesthesiologist and the surgeon as well as excellent cooperation between the surgeon and anesthesiologist with a tacit understanding of the peri-operative risks. Peri-operative risk factors have been readily investigated in Caucasians or Westerners. As different ethnic populations may have different risk factors for a same disease entity, understanding the uniqueness in this respect in Taiwanese is mandatory. The purpose of this study is to examine the risk factors, perioperative cardiac events and the qualities of preoperative preparation and post-operative intensive care in Taiwanese cardiac patients undergoing noncardiac surgery. METHODS: Two medical centers in Taiwan worked out a set of prospective questionnaire to evaluate the preoperative preparation, intraoperative events, and postoperative care of cardiac patients undergoing noncardiac surgery in these hospitals. RESULTS: Between March 2002 and May 2002, there were 196 cardiac patients undergoing noncardiac surgery out of a total of 10,129 anesthetized surgical patients in two medical centers. The risk factors of these patients included coronary artery disease, hypertension, diabetes mellitus, congestive heart failure, arrhythmia, and renal function impairment. In these 196 cases, only 26.5% (52) and 16.8% (33) had been preoperatively evaluated by cardiologist and anesthesiologist respectively through consultation. The number of pre-operation specific cardiac tests totaled 34, and 41 patients (20.9%) required post-operative intensive care. There were two peri-operative fatalities and fourteen peri-operative cardiac events. CONCLUSIONS: The quality of care for preoperative evaluation and quality assurance need to be improved in Taiwan.