Anti-microRNA-1976 as a Novel Approach to Enhance Chemosensitivity in XAF1+ Pancreatic and Liver Cancer.

The current cancer treatments using chemoagents are not satisfactory in terms of outcomes and prognosis. Chemoagent treatments result in cell death or arrest, but the accompanying cellular responses are not well-studied. Exosomes, which are extracellular vesicles secreted by living cells, might mediate cellular responses through microRNAs. We found that miR-1976 was highly enriched in exosomes secreted after chemoagent treatment. We developed a novel approach for in situ mRNA target screening and discovered several miR-1976-specific mRNA targets, including the proapoptotic gene XAF1, which was targeted by miR-1976 and which suppressed chemoagent-induced cell apoptosis. Increased RPS6KA1 gene transcription was associated with the increase in its intronic pre-miR-1976 expression. Blockade of miR-1976 could enhance chemosensitivities of hepatoma and pancreatic cancer cells in an XAF1-dependent manner, as evidenced by increased levels of cell apoptosis, reduced IC50 in cell toxicity assays, and suppressed tumor growth in animal xenograft experiments in vivo. We propose that intracellular levels of miR-1976 determine chemosensitivity, and its blockade could be a novel strategy and potential therapeutic application in cancer treatment.

Outcomes of laparoscopic cholecystectomy in patients with and without COPD.

Objective: The aim of this study was to investigate the outcomes of patients with COPD after laparoscopic cholecystectomy (LC). Patients and methods: All COPD patients who underwent LC from 2000 to 2010 were identified from the Taiwanese National Health Insurance Research Database. The outcomes of hospital stay, intensive care unit (ICU) stay, and use of mechanical ventilation and life support measures in COPD and non-COPD populations were compared. Results: A total of 3,954 COPD patients who underwent LC were enrolled in our study. There were significant differences in the hospitalization period, ICU stay, and use of mechanical ventilation and life support measures between the COPD and non-COPD populations. The mean hospital stay, ICU stay and number of mechanical ventilation days in the COPD and non-COPD groups were 7.81 vs 6.01 days, 5.5 vs 4.5 days and 6.40 vs 4.74 days, respectively. The use of life support measures, including vasopressors and hemodialysis, and the rates of hospital mortality, acute respiratory failure and pneumonia were also increased in COPD patients compared with those in non-COPD patients. Conclusion: COPD increased the risk of mortality, lengths of hospital and ICU stays, ventilator days and poor outcomes after LC in this study.

The impact of young age on the prognosis for colorectal cancer: a population-based study in Taiwan.

BACKGROUND: The impact of age as a prognostic factor for patients with colorectal cancer (CRC) remains controversial, possibly due to heterogeneity between studies in terms of patient numbers, percentage of patients undergoing curative resection, percentage of patients receiving neoadjuvant therapy, or failure to adjust for potential confounding factors. This study used colorectal cancer survival data from the Taiwan Cancer Registry database in order to comprehensively analyze age as a prognostic factor. METHODS: Survival data were analyzed for 62 060 CRC patients diagnosed with adenocarcinoma, mucinous adenocarcinoma, or signet-ring cell carcinoma of the colon and rectum between 1998 and 2005. The rates of all-cause mortality and CRC-related mortality were determined using Kaplan-Meier analysis, and the log-rank test was used to compare differences in survival between different age groups. The crude and adjusted hazard ratios for all-cause and CRC-related mortalities were calculated according to the estimates from the univariable and multivariable Cox proportional hazard models. RESULTS: Patients in the ≤40 and the 41-50 age groups had a higher proportion of mucinous adenocarcinoma (P < 0.001) and signet-ring cell carcinoma (P < 0.001) compared to the older age groups. After adjusting for gender, histology, and tumor site, patients in the ≤40 age group had a poorer overall survival (OS) and cancer-specific survival compared to patients in the 41-50 and 51-60, and 61-70 age groups (P < 0.001), but a better OS and cancer-specific survival compared to patients in the 71-80 and >80 age groups (P < 0.001). CONCLUSIONS: Our study indicated that age is an important consideration while determining the clinical management of CRC patients.

The Association Between Ventriculo-Peritoneal Shunt and Acute Appendicitis in Patients with Traumatic Brain Injury: A 14-Year, Population-Based Study.

OBJECTIVE: The association between preexisting ventriculoperitoneal (VP) shunt and the risk of new-onset acute appendicitis in patients with traumatic brain injury (TBI) is not well established. The aim of the present study was to determine the relationships between VP shunt and acute appendicitis in patients with TBI. METHODS: A longitudinal cohort study matched by a propensity score in patients with TBI with (4781 patients) or without (9562 patients) VP shunt was conducted using the National Health Insurance Research Database in Taiwan between January 1993 and December 2013. RESULTS: The main outcome studied was diagnosis of acute appendicitis. The cumulative probability of acute appendicitis was not different between these 2 groups (P = 0.6244). A Cox model showed central nervous system (CNS) infection to be an independent predictor of acute appendicitis with an adjusted hazard ratio of 2.98. Patients with TBI with both a VP shunt and a CNS infection had a greater risk of developing new-onset acute appendicitis (hazard ratio 4.25; 95% confidence interval 1.84-9.81) compared patients with TBI without a VP shunt or CNS infection. CONCLUSIONS: We concluded that VP shunt is not a risk factor in the development of appendicitis in patients with TBI. Patients with TBI with a shunt and a CNS infection may have a greater risk of developing acute appendicitis. Therefore, care in avoiding CNS infection is a key for the prevention acute appendicitis in this patient population.

Factors Associated With Small Bowel Obstruction Following Appendectomy: A Population-Based Study.

Postoperative small bowel obstruction (SBO) is a common complication of appendectomy. This study aimed to assess risk factors for SBO following appendectomy.This retrospective cohort study used the 2006 to 2008 Taiwan National Health Insurance Research Database. We evaluated adult patients with acute appendicitis who underwent open (OA) or laparoscopic appendectomy (LA) between January 1, 2006 and December 31, 2008. Excluded were patients with a history of abdominal surgery and SBO before the index operation, or abdominal surgery between the appendectomy and initial diagnosis of bowel obstruction as an identifiable cause of SBO. Factors thought to influence postoperative SBO were highlighted. The OA and LA cohorts were matched by propensity score, and the hazard ratios (HRs) and 95% confidence interval (CIs) of SBO were calculated.We enrolled 11,289 patients who underwent OA, and 11,289 matched controls who underwent LA. OA patients had significant risk of adhesive SBO compared with the LA group (adjusted HR: 1.7, 95% CI: 1.11-2.63). Further analysis revealed that that female sex (adjusted HR: 1.79, 95% CI: 1.17-2.72), CCI score of 1 or ≥2 (adjusted HR: 3.16, 95% CI: 1.76-5.67; adjusted HR: 4.03, 95% CI: 1.57-10.34), complicated appendicitis (adjusted HR: 1.68, 95% CI: 1.05-2.69), treatment in district hospitals increased risk of adhesive SBO.Female sex, complicated appendicitis, more comorbidities, and treatment in district hospitals are factors associated with a risk of SBO after appendectomy. Our findings confirmed that a laparoscopic approach is better than an open approach.

Mortality in Emergency Department Sepsis score as a prognostic indicator in patients with pyogenic liver abscess.

OBJECTIVES: The purpose of this study was to explore the predictor index of mortality in patients with pyogenic liver abscess (PLA). METHODS: We performed a retrospective review that enrolled 431 patients 18 years and older hospitalized due to PLA between January 2005 and December 2010. Clinical characteristics, laboratory results, treatments, and outcomes retrieved from medical records were analyzed. Multiple logistic regression and receiver operating characteristic curve analyses were performed. RESULTS: The mean age of the 431 patients identified with PLA was 56.9 ± 15.0 years. The mean Mortality in Emergency Department Sepsis (MEDS) score on admission was 4.8 ± 4.1 (range, 0-17). During hospitalization, 94 patients (22%) required intensive care. Of the 431 patients, 63 died, yielding a 15% case fatality rate. Multivariate analysis revealed that higher MEDS scores on admission (P < .0001) and the presence of underlying malignancy (P = .006), multiple abscesses (P = .001), anaerobic infections (P < .0001), hyperbilirubinemia (P < .0001), and higher serum creatinine levels (P < .0001) were significantly associated with PLA mortality. The estimated area under the receiver operating characteristic curve for MEDS in predicting PLA mortality was 0.829 (95% confidence interval, 0.791-0.864; P < .0001). The optimal cutoff MEDS value of 7 or higher had a sensitivity of 76% sensitivity and a specificity of 81%, with a 10.7-fold PLA mortality risk (P < .0001) and a 26.2-fold intensive care unit admission risk (P < .0001). CONCLUSIONS: The MEDS scores on admission represent a significant prognostic indicator for patients with PLA.