Retrograde transvenous obliteration for the prevention of variceal rebleeding in patients with hepatocellular carcinoma: a multicentre retrospective study.

AIM: To evaluate the effectiveness and safety of retrograde transvenous obliteration (RTO) for the prevention of variceal rebleeding variceal rebleeding in patients with hepatocellular carcinoma (HCC). MATERIALS AND METHODS: This multicentre retrospective study enrolled 79 patients with HCC who underwent RTO for the prevention of variceal rebleeding. Successful occlusion of the gastrorenal shunt and obliteration of the gastric varices were achieved in 74 patients, with a technical success rate of 93.7%. Of the remaining 74 patients (mean age, 64.9±10.3 years; 56 men), 66 (90.4%) had gastroesophageal varices and seven (9.6%) had isolated gastric varices. Thirty-two patients (43.8%) underwent balloon-occluded RTO, 40 patients (54.8%) underwent plug-assisted RTO, and one patient (1.4%) underwent coil-assisted RTO. No patients had major procedural complications. RESULTS: Rebleeding occurred in seven patients (9.6%) during the follow-up period. The 6-week and 1-year actuarial probabilities of patients remaining free of rebleeding were 90.8±3.6% and 88.6±4.1%, respectively. The median survival was 12.6 (95% confidence interval [CI] 8-17.3) months. The 6-week, 1-year, and 3-year actuarial probabilities of survival were 83.2±4.4%, 51.1±6.6%, and 32.7±7%, respectively. New or worsening ascites and oesophageal varices occurred in 12 (16.4%) and 13 patients (17.8%), respectively, during the follow-up period. Overt hepatic encephalopathy occurred in one patient (1.4%) during the follow-up period. The Child-Pugh score remained comparable to that at baseline at 1 and 3 months. CONCLUSION: RTO was effective and safe in preventing variceal rebleeding in patients with HCC.

The alternative complement pathway in ANCA-associated vasculitis: further evidence and a meta-analysis.

We compared the common pathway components C3a, C5a and membrane attack complex (MAC), also known as C5b-9, and the alternative pathway components factor B and properdin in patients with ANCA-associated vasculitis (AAV) and healthy controls, and conducted a meta-analysis of the available clinical evidence for the role of complement activation in the pathogenesis of AAV. Complement components were evaluated in 59 patients with newly diagnosed or relapsing granulomatosis with polyangiitis or microscopic polyangiitis and 36 healthy volunteers. In 28 patients, testing was repeated in remission. Next, we performed a meta-analysis by searching databases to identify studies comparing complement levels in AAV patients and controls. A random-effects model was used for statistical analyses. The median concentrations of MAC, C5a, C3a and factor B were higher in active AAV patients (P < 0·001). Achievement of remission was associated with reductions in C3a (P = 0·005), C5a (P = 0·035) and factor B levels (P = 0·045), whereas MAC and properdin levels did not change. In active AAV, there were no effects of ANCA specificity, disease phenotype, previous immunosuppression or disease severity on complement levels. A total of 1122 articles were screened, and five studies, including this report, were entered into the meta-analysis. Plasma MAC, C5a and factor B in patients with active AAV were increased compared to patients in remission (excluding factor B) and controls. Changes in C3a were of borderline significance. Our findings and the results of the meta-analysis support activation of the complement system predominantly via the alternative pathway in AAV patients.

The effect of cricoid and paralaryngeal force on upper oesophageal occlusion during induction of anaesthesia: a randomised, crossover study.

The aim of this study was to evaluate the effectiveness of cricoid and paralaryngeal force for oesophageal entrance occlusion during induction of anaesthesia. Seventy-four patients were included in this randomised, crossover study. The relative position of the glottis and outer anteroposterior diameter of the upper oesophageal entrance were assessed at baseline, after the application of 30 N cricoid and paralaryngeal force, and after induction of anaesthesia. The occlusion rate of the oesophageal entrance with cricoid and paralaryngeal force was assessed during direct laryngoscopy. The relative position of the upper oesophageal entrance to the glottis changed in 45 out of 74 patients after induction of anaesthesia and during direct laryngoscopy compared with the awake state. The application of cricoid and paralaryngeal force decreased the mean (SD) diameter of the upper oesophageal entrance to a similar degree in awake (8.5 (2.1) mm to 6.4 (1.7) mm and 6.5 (1.6) mm, respectively; p < 0.001) and anaesthetised (8.7 (2.2) mm to 6.5 (1.7) mm and (6.7 (1.9) mm, respectively; p < 0.001) states. During direct laryngoscopy, the occlusion rate of the oesophageal entrance was greater with cricoid compared with paralaryngeal force (46/74 vs. 26/74, respectively; p = 0.002). The relative position of the upper oesophageal entrance to the glottis may change after induction of anaesthesia and during direct laryngoscopy. Cricoid and paralaryngeal force both decrease the diameter of the upper oesophageal entrance in awake and anaesthetised states. Occlusion of the oesophageal entrance is achieved more frequently with cricoid force compared with paralaryngeal force during direct laryngoscopy.

Overall survival and updated progression-free survival outcomes in a randomized phase II study of combination cediranib and olaparib versus olaparib in relapsed platinum-sensitive ovarian cancer.

BACKGROUND: Olaparib is a poly(ADP-ribose) polymerase inhibitor and cediranib is an oral anti-angiogenic. In the primary analysis of this phase II study, combination cediranib/olaparib improved progression-free survival (PFS) compared with olaparib alone in relapsed platinum-sensitive ovarian cancer. This updated analysis was conducted to characterize overall survival (OS) and update PFS outcomes. PATIENTS AND METHODS: Ninety patients were enrolled to this randomized, open-label, phase II study between October 2011 and June 2013 across nine United States-based academic centers. Data cut-off was 21 December 2016, with a median follow-up of 46 months. Participants had relapsed platinum-sensitive ovarian cancer of high-grade serous or endometrioid histology or had a deleterious germline BRCA1/2 mutation (gBRCAm). Participants were randomized to receive olaparib capsules 400 mg twice daily or cediranib 30 mg daily and olaparib capsules 200 mg twice daily until disease progression. RESULTS: In this updated analysis, median PFS remained significantly longer with cediranib/olaparib compared with olaparib alone (16.5 versus 8.2 months, hazard ratio 0.50; P = 0.007). Subset analyses within stratum defined by BRCA status demonstrated statistically significant improvement in PFS (23.7 versus 5.7 months, P = 0.002) and OS (37.8 versus 23.0 months, P = 0.047) in gBRCA wild-type/unknown patients, although OS was not statistically different in the overall study population (44.2 versus 33.3 months, hazard ratio 0.64; P = 0.11). PFS and OS appeared similar between the two arms in gBRCAm patients. The most common CTCAE grade 3/4 adverse events with cediranib/olaparib remained fatigue, diarrhea, and hypertension. CONCLUSIONS: Combination cediranib/olaparib significantly extends PFS compared with olaparib alone in relapsed platinum-sensitive ovarian cancer. Subset analyses suggest this margin of benefit is driven by PFS prolongation in patients without gBRCAm. OS was also significantly increased by the cediranib/olaparib combination in this subset of patients. Additional studies of this combination are ongoing and should incorporate analyses based upon BRCA status. TRIAL REGISTRATION: Clinicaltrials.gov Identifier NCT0111648.

A simulation impact evaluation of a cigarette excise tax increase on licit and illicit cigarette consumption and tax revenue in 36 European countries.

OBJECTIVES: To assess the impact of a simulated 10% tax-induced cigarette price increase on licit and illicit consumption and tax revenues in 36 European countries. METHODS: Employing panel data for licit and illicit cigarette consumption, fixed effects regression models were applied for different income clusters. RESULTS: Total cigarette consumption dropped by about 3.1% as a result of the simulated tax-induced price increase. Annual illicit cigarette consumption increased by 1.52%, (95% confidence interval: 0.21, 2.83), while annual licit cigarette consumption decreased by 4.61% (95% confidence interval: -6.51, -2.72) in the observed 36 European countries. With total consumption decreasing by about 8%, the Czech Republic, Latvia, Lithuania, Poland and Slovakia were affected the most by the price hike. More specifically, licit consumption in these countries decreased by 18.43% (95% confidence interval: -19.91, -16.95) while illicit use increased by 10.99% (95% confidence interval: 6.01, 15.96). Moreover, the overall annual tobacco tax revenue increased by US$14.69 billion in the simulation. CONCLUSION: Results of the study suggest that European policy makers continue to implement tobacco taxation policies to control smoking prevalence and national health care expenditures. At the same time, efforts to kerb contraband activities along EU Eastern borders should be intensified.

Comparison of overall survival between antiviral-induced viral suppression and inactive phase chronic hepatitis B patients.

Nucleot(s)ide analogues (NAs) reduce the risk of hepatocellular carcinoma (HCC) in chronic hepatitis B (CHB) patients. However, the risk of HCC is reportedly higher for NA-treated patients than for patients in the inactive CHB phase. This study aimed to compare the long-term outcomes of CHB patients with NA-induced viral suppression and those of patients with inactive CHB. This retrospective study involved 1118 consecutive CHB patients whose HBV DNA level was continuously <2000 IU/mL during follow-up with/without antiviral agents. The patients were classified into inactive CHB (n = 373) or NA groups (n = 745). The primary endpoint was overall survival. Secondary endpoints included development of HCC and other liver-related events. The median duration of follow-up was 41.0 (interquartile range = 26.5-55.0) months. The difference in overall survival between the NA group vs. the inactive CHB group was not significant (hazard ratio [HR] = 0.78; 95% confidence interval [CI] = 0.33-1.85; P = .57). The NA group showed a significantly higher risk of HCC (HR = 3.44; 95% CI = 1.82-6.52; P < .01), but comparable risk for non-HCC liver-related events (HR = 1.02; 95% CI = 0.66-1.59; P = .93), compared with the inactive CHB group. Among patients with cirrhosis, the NA group showed a significantly lower risk of death (HR = 0.31; 95% CI = 0.097-0.998; P = .05) and non-HCC liver-related events (HR = 0.51; 95% CI = 0.31-0.83; P < .01), but a slightly higher risk of HCC (HR = 2.39; 95% CI = 0.85-6.75; P = .09), compared to the inactive CHB group. The overall survival of untreated patients with inactive CHB and of CHB patients achieving viral suppression with NA was comparable. However, NA treatment of cirrhotic patients was significantly associated with longer overall survival and lower risk of liver-related events.

Electroencephalographic markers of brain development during sevoflurane anaesthesia in children up to 3 years old.

BACKGROUND: General anaesthetics generate spatially defined brain oscillations in the EEG that relate fundamentally to neural-circuit architecture. Few studies detailing the neural-circuit activity of general anaesthesia in children have been described. The study aim was to identify age-related changes in EEG characteristics that mirror different stages of early human brain development during sevoflurane anaesthesia. METHODS: Multichannel EEG recordings were performed in 91 children aged 0-3 yr undergoing elective surgery. We mapped spatial power and coherence over the frontal, parietal, temporal, and occipital cortices during maintenance anaesthesia. RESULTS: During sevoflurane exposure: (i) slow-delta (0.1-4 Hz) oscillations were present in all ages, (ii) theta (4-8 Hz) and alpha (8-12 Hz) oscillations emerge by ∼4 months, (iii) alpha oscillations increased in power from 4 to 10 months, (iv) frontal alpha-oscillation predominance emerged at ∼6 months, (v) frontal slow oscillations were coherent from birth until 6 months, and (vi) frontal alpha oscillations became coherent ∼10 months and persisted in older ages. CONCLUSIONS: Key developmental milestones in the maturation of the thalamo-cortical circuitry likely generate changes in EEG patterns in infants undergoing sevoflurane general anaesthesia. Characterisation of anaesthesia-induced EEG oscillations in children demonstrates the importance of developing age-dependent strategies to monitor properly the brain states of children receiving general anaesthesia. These data have the potential to guide future studies investigating neurodevelopmental pathologies involving altered excitatory-inhibitory balance, such as epilepsy or Rett syndrome.

Intensity of surveillance for hepatocellular carcinoma determines survival in patients at risk in a hepatitis B-endemic area.

BACKGROUND: Data are insufficient regarding the survival benefit of surveillance for hepatocellular carcinoma (HCC). AIM: To investigate the effectiveness of HCC surveillance in a hepatitis B-endemic population. METHODS: This retrospective cohort study included 1402 consecutive patients who were newly diagnosed with HCC between 2005 and 2012 at a single tertiary hospital in Korea. The primary endpoint was overall survival. Lead-time and length-time biases were adjusted (sojourn time = 140 days) and sensitivity analyses were performed. RESULTS: The most common aetiology was hepatitis B (80.4%). Cirrhosis was present in 78.2%. HCC was diagnosed during regular surveillance (defined as mean interval of ultrasonography <8 months, n = 834), irregular surveillance (n = 104) or nonsurveillance (n = 464). Patients in the regular surveillance group were diagnosed at earlier stages ([very] early stage, 64.4%) than the irregular surveillance (40.4%) or nonsurveillance (26.9%) groups and had more chance for curative treatments (52.4%) than the irregular surveillance (39.4%) or nonsurveillance (23.3%) groups (all P < 0.001). Mortality risk was significantly lower in the regular surveillance group (adjusted hazard ratio [aHR], 0.69; 95% [CI], 0.57-0.83) but not in the irregular surveillance group (aHR, 0.94; 95% CI, 0.69-1.28) compared with the nonsurveillance group after adjusting for confounding factors and lead-time. When the subjects were restricted to cirrhotic patients or Child-Pugh class A/B patients, similar results were obtained for mortality risk reduction between groups. CONCLUSIONS: HCC surveillance was associated with longer survival owing to earlier diagnosis and curative treatment. Survival advantage was significant with regular surveillance but not with irregular surveillance.

Clinical Implication of Tests for Prostate-specific Antigen in Brain-dead Organ Donors.

BACKGROUND: Although cancer screening tests are not mentioned under brain-dead organ donor care guidelines in Korea, we assessed the level of prostate-specific antigen (PSA), an important prostate cancer marker, and performed prostate biopsies when needed in brain-dead organ donors. We believe that insisting on a screening test for cancer diagnosis in donors' organs is important. MATERIALS AND METHODS: Data were collected between January 2010 and July 2015 from Ajou University Hospital. We retrospectively analyzed the PSA levels and prostate biopsy results in 111 male brain-dead organ donors (mean age, 48.4 years). RESULTS: The mean PSA level was 7.395 ng/mL (range, 0.062 to 61.780; reference, 0 to 4 ng/mL). Ultrasonography or computed tomographic examination did not reveal prostate cancer, and a rectal examination was not performed. After checking the PSA levels, prostate biopsies were performed in 16 patients based on the recommendations of a urologist, and 4 patients (3.6% of 111) were diagnosed with prostate cancer. All cancers involved adenocarcinomas (acinar type) histopathologically. In 2 patients, the Gleason score was 6 (3 + 3), whereas the other 2 showed a score of 7 (3 + 4). Among the patients diagnosed with prostate cancer, 1 donated his liver and corneas, and the remaining 3 could not donate. CONCLUSION: Well-defined cancer screening tests are needed in Korea. Additionally, when the probability of organ transplantation-induced cancer metastasis is low or a recipient is at a high risk owing to not receiving organs, the law should allow organ donation even if prostate cancer is diagnosed in the donor.

Entecavir and tenofovir reduce hepatitis B virus-related hepatocellular carcinoma recurrence more effectively than other antivirals.

Nucleos(t)ide analogues (NAs) have been shown to decrease the risk of hepatocellular carcinoma (HCC) recurrence. This study evaluated whether high-potency NAs (entecavir and tenofovir disoproxil fumarate [TDF]) reduce the risk of tumour recurrence more potently than low-potency NAs after curative treatment of hepatitis B virus (HBV)-related HCC. This study included 607 consecutive HBV-related HCC patients treated with surgical resection or radiofrequency ablation. The patients were categorized into three groups according to antiviral treatment: group A (no antiviral; n = 261), group B (low-potency NA; n = 90) and group C (high-potency NA; n = 256). The primary end-point was recurrence-free survival (RFS). During the duration of follow-up, the median RFS was 29.4, 25.1, and 88.2 months in groups A, B and C, respectively (P < .001, log-rank test). The multivariate Cox analysis indicated that group C had a significantly longer RFS than both group A (adjusted hazard ratio [HR] = 0.39, P < .001) and group B (adjusted HR = 0.47, P < .001). When baseline characteristics were balanced using inverse probability weighting, group C still had a significantly longer RFS than group A (adjusted HR = 0.46, P < .001) and group B (adjusted HR = 0.59, P = .007). Group C had significantly lower risk of viral breakthrough than group B (HR = 0.19, P < .001). Viral breakthrough was an independent risk factor for shorter RFS among groups B and C (adjusted HR = 2.03, P = .007, time-dependent Cox analysis). Antiviral agents with high genetic barrier to resistance (entecavir and TDF) reduced the risk of HCC recurrence compared with other antivirals and no antiviral treatment, especially in patients with high baseline viral load.

Activity measurement of 222Rn gas for a key comparison.

The Korea Research Institute of Standards and Science (KRISS) participated, in 2015, in an international Key Comparison (KC) of gaseous radon-222 activity named CCRI (II) -K2.Rn-222 to confirm international equivalence of KRISS-established gaseous radon-222 measurement standards. LNHB acted as KC pilot laboratory. This paper describes the KC measurement procedure followed at KRISS using the defined solid angle counting method together with auxiliary relative measurement methods and presents the results.

Association of high-dose postoperative opioids with recurrence risk in esophageal squamous cell carcinoma: reinterpreting ERAS protocols for long-term oncologic surgery outcomes.

Esophageal squamous cell carcinoma (ESCC) is associated with a poor prognosis and high postoperative recurrence rate. Although postoperative opioid use has been associated with cancer recurrence, its relevance in ESCC has not been determined. Therefore, this study investigated whether high-dose postoperative opioid use was associated with recurrence risk in patients with ESCC. For this retrospective analysis, the medical records of patients who were diagnosed with ESCC and who underwent surgery between January 2006 and December 2010 in the National Cancer Center, Korea were evaluated. Total opioid administration over a 10-day period, from during surgery to postoperative day 9, was calculated. A cutoff value was determined using receiver operating characteristic curve analysis, and patients were classified into the high-use and low-use groups. The primary and secondary outcomes of the study were freedom from recurrence and overall survival, respectively. After propensity score matching, the effect of opioid use on freedom from recurrence and overall survival was evaluated using the Kaplan-Meier method. The final analysis set included 258 patients. The cumulative opioid dose cutoff point was 1783.5 mg of oral morphine. High-dose postoperative opioid use was a significant factor affecting recurrence (Hazard ratio [HR], 2.162; 95% confidence interval [CI], 1.583-2.954; P < 0.0001). In contrast, postoperative opioid use was not associated with death (HR, 1.274; 95% CI, 0.922-1.761; P = 0.1422). In patients with ESCC, compared with low-dose opioid use, high-dose intraoperative and postoperative opioid use was significantly associated with an increased risk of recurrence. However, opioid dosage did not affect overall survival.

Benefits of active middle ear implants over hearing aids in patients with sloping high tone hearing loss: comparison with hearing aids.

In this retrospective chart review we compared the subjective and objective benefits of active middle ear implants (AMEIs) with conventional hearing aids (HAs) in patients with sloping high tone hearing loss. Thirty-four patients with sensorineural hearing loss were treated with AMEIs. Of these, six had sloping high tone hearing loss and had worn an HA for more than 6 months. Objective assessments, a pure-tone audiogram, as well as a word recognition test, and the Korean version of the Hearing in Noise Test (K-HINT), and a subjective assessment, the Abbreviated Profile of Hearing Aid Benefit (APHAB) questionnaire, were performed. Tests were conducted under three circumstances: 1) the unaided state before surgery; 2) the HA-aided state before surgery; and 3) the AMEI-aided state 3 months after surgery. The average high-frequency hearing gain (≥ 2 kHz) was significantly better with AMEIs than with HAs. Although the result had no statistical significance, AMEIs showed a superior word recognition score (WRS) compared to HAs. However, the most comfortable hearing level at which the WRS was tested was significantly decreased with an AMEI compared to an HA. In the K-HINT, patients with an AMEI showed greater recognition than those fitted with an HA under both quiet and noisy conditions. The APAHB scores revealed that patients were more satisfied with an AMEI rather than an HA on all subscales. The use of vibroplasty in patients with sloping high tone loss resulted in positive hearing outcomes when compared to conventional HAs. Based on the data from this study, AMEIs provided better objective and subjective results and could, therefore, be a better alternative for the treatment of sloping hearing loss.

Mulberry leaf extract fermented with Lactobacillus acidophilus A4 ameliorates 5-fluorouracil-induced intestinal mucositis in rats.

The objective of the present study was to evaluate the effect of mulberry leaf extract (ME) fermented with Lactobacillus acidophilus A4 (A4) on intestinal mucositis induced by 5-fluorouracil (5-FU) in a rat model. Male Wistar rats were gavaged with A4, ME, fermented mulberry leaf extract FME) or lafutidine (LAF) for 10 days and injected intraperitoneally with 5-FU (150 mg kg-1 ) or saline (normal control) on day 7 to induce mucositis. After euthanizing the animals, their small and large intestines were removed for evaluation of histopathologic parameters, myeloperoxidase (MPO) activity, mucin content, and mRNA expression of the mucin gene and pro-inflammatory cytokine interleukin (IL)-1ß. 5-FU induced significant weight loss, shortened villi height, and increased histological severity, IL-1ß expression, and MPO activity compared to the normal control group. These pathological changes were markedly ameliorated by treatment with A4, ME and FME. These treatments also stimulated MUC2 and MUC5AC gene expression and mucin production, and reduced IL-1ß expression and MPO level. Interestingly, FME had the greatest protective effect on 5-FU-induced mucositis in rats. SIGNIFICANCE AND IMPACT OF THE STUDY: Our results suggest that fermented mulberry leaf extract (ME) may provide synergistic therapeutic benefits of both probiotics and natural plant extracts in prevention of 5-fluorouracil-induced mucositis. These impacts are particularly significant given the induction of MUC2 and MUC5AC gene expressions for production of mucins and the reduction of pro-inflammatory cytokine interleukin-1ß in gut environments. Therefore, we proposed that enhanced functionality of ME by fermentation of Lactobacillus acidophilus A4 can be applied as food-grade adjuncts for mucositis therapy and prevention in food industry.

Cytosolic PKM2 stabilizes mutant EGFR protein expression through regulating HSP90-EGFR association.

This corrects the article DOI: 10.1038/onc.2015.397.

Adenovirus-mediated Foxp3 expression in lung epithelial cells ameliorates acute radiation-induced pneumonitis in mice.

Forkhead transcription factor 3 (Foxp3) has a critical role in regulatory T cells (Treg). There are an increasing number of researches concerning the functions of Foxp3 in other cells, including lung epithelial cells besides Treg. However, the roles of Foxp3 in lung epithelial cells remain poorly understood. To examine the potential therapeutic benefits of Foxp3 for lung inflammation, this study investigates the effect of adenovirus-mediated Foxp3 overexpression in a radiation-induced lung damage model. Foxp3-EGFP expressing adenovirus was administered by intratracheal injection three times over 14 days after focal X-ray irradiation. To evaluate effects of Foxp3 overexpression in radiation-induced lung inflammation, immune cell profiles of bronchoalveolar lavage (BAL) fluid were analyzed. Foxp3 gene-delivered mice showed significant inhibition of immune cell infiltration, such as eosinophils, lymphocytes, macrophages and neutrophils in BAL fluid. Histopathological analysis also showed that Foxp3 overexpression inhibits inflammatory cell recruitment and collagen deposition in lung tissues. In addition, expression of inflammatory and fibrosis-related genes was decreased in the Foxp3 expression adenovirus-infected group. These results suggest that Foxp3 expression in lungs holds considerable therapeutic potential for attenuating inflammation and fibrosis in radiation-induced lung injury.

Prognostic significance of venous invasion and maximum standardized uptake value of 18F-FDG PET/CT in surgically resected T1N0 esophageal squamous cell carcinoma.

BACKGROUND: The purpose of this study was to analyze the risk factors of recurrence in patients with early stage esophageal squamous cell carcinoma (ESCC). METHODS: We retrospectively analyzed the medical records of 190 patients with confirmed T1N0M0 ESCC after curative esophagectomy. The following potential prognostic factors for recurrence were investigated: age, sex, pathologic T category, tumor location, differentiation grade, tumor size, venous invasion, angiolymphatic invasion, perineural invasion and the maximum standardized uptake value (SUVmax) of the primary tumor. RESULTS: There were 174 male and 16 female patients with a median age of 66.0 years (range, 42.0-79.0 years). The pathologic status of the surgically resected ESCCs was T1a in 93 patients (48.9%) and T1b in 97 patients (51.1%). The median number of dissected lymph nodes was 35 (range, 10 to 86), and all lymph nodes were negative for tumors. The multivariate analysis showed presence of venous invasion [HR (hazard ratio), 11.433; P < 0.001) and SUVmax ≥ 3.2 (HR, 2.830; P = 0.011) as independent risk factors for recurrence. The 5-year recurrence-free survival (RFS) was 25.0% for patients with venous invasion and 78.9% for those without (P < 0.001). The 5-year RFS was 67.1% for patients with an SUVmax ≥3.2 and 81.5% for those with an SUVmax <3.2 (P = 0.003). CONCLUSIONS: Venous invasion and high SUVmax could be important prognostic factors coupled with the TNM staging system, in patients with early stage ESCC.

TFAP2C promotes lung tumorigenesis and aggressiveness through miR-183- and miR-33a-mediated cell cycle regulation.

Non-small cell lung cancer (NSCLC) remains one of the leading causes of death worldwide, and thus new molecular targets need to be identified to improve treatment efficacy. Although epidermal growth factor receptor (EGFR)/KRAS mutation-driven lung tumorigenesis is well understood, the mechanism of EGFR/KRAS-independent signal activation remains elusive. Enhanced TFAP2C (transcription factor activating enhancer-binding protein 2C) expression is associated with poor prognosis in some types of cancer patients, but little is known of its relation with the pathogenesis of lung cancer. In the present study, we found that TFAP2C overexpression was associated with cell cycle activation and NSCLC cell tumorigenesis. Interestingly, TFAP2C blocked AKAP12-mediated cyclin D1 inhibition by inducing the overexpression of oncogenic microRNA (miRNA)-183 and simultaneously activated cyclin-dependent kinase 6-mediated cell cycle progression by downregulating tumor-suppressive miRNA-33a. In a mouse xenograft model, TFAP2C promoted lung tumorigenesis and disease aggressiveness via the miR-183 and miR-33a pathways. The study provides a mechanism of mitogenic and oncogenic signaling via two functionally opposed miRNAs and suggests that TFAP2C-induced cell cycle hyperactivation contributes to lung tumorigenesis.