Hepatocellular carcinoma (HCC) is one of the fastest‐rising causes of cancer‐related death worldwide, but its deficiency of specific biomarkers and therapeutic targets in the early stages lead to severe inadequacy in the early diagnosis and treatment of HCC. Covalently closed circular RNA (circRNA), which was once considered an aberrant splicing by‐product, is now drawing new interest in cancer research because of its remarkable functionality. Beneath the surface of the dominant functional proteins events, a hidden circRNA‐centric noncoding regulatory RNAs network active in the very early stage of HCC is here revealed by a genome‐wide analysis of mRNA, circRNA, and microRNA (miRNA) expression profiles. Circ‐CDYL (chromodomain Y like) is specifically up‐regulated in the early stages of HCC and therefore contributes to the properties of epithelial cell adhesion molecule (EPCAM)‐positive liver tumor‐initiating cells. Circ‐CDYL interacts with mRNAs encoding hepatoma‐derived growth factor (HDGF) and hypoxia‐inducible factor asparagine hydroxylase (HIF1AN) by acting as the sponge of miR‐892a and miR‐328‐3p, respectively. Subsequently, activation of the phosphoinositide 3‐kinase (PI3K)‐AKT serine/threonine kinase‐mechanistic target of rapamycin kinase complex 1/β‐catenin and NOTCH2 pathways, which promote the expression of the effect proteins, baculoviral IAP repeat containing 5 (BIRC5 or SURVIVIN) and MYC proto‐oncogene, is influenced by circ‐CDYL. A treatment incorporating circ‐CDYL interference and traditional enzyme inhibitors targeting PI3K and HIF1AN demonstrated highly effective inhibition of stem‐like characteristics and tumor growth in HCC. Finally, we demonstrated that circ‐CDYL expression or which combined with HDGF and HIF1AN are both independent markers for discrimination of early stages of HCC with the odds ratios of 1.09 (95% confidence interval [CI], 1.02‐1.17) and 124.58 (95% CI, 13.26‐1170.56), respectively. Conclusion: These findings uncover a circRNA‐centric noncoding regulatory RNAs network in the early stages of HCC and thus provide a possibility for surveillance and early treatment of HCC.

Early and late recurrences of solitary HCC after curative resection are associated with different predictive factors. The time to recurrence and further curative treatment after recurrence were the best predictors of survival post recurrence.

BackgroundPreoperative jaundice is frequent in gallbladder cancer (GBC) and indicates advanced disease. Resection is rarely recommended to treat advanced GBC. An aggressive surgical approach for advanced GBC remains lacking because of the association of this disease with serious postoperative complications and poor prognosis. This study aims to re-assess the prognostic value of jaundice for the morbidity, mortality, and survival of GBC patients who underwent surgical resection with curative intent.MethodsGBC patients who underwent surgical resection with curative intent at a single institution between January 2003 and December 2012 were identified from a prospectively maintained database.ResultsA total of 192 patients underwent surgical resection with curative intent, of whom 47 had preoperative jaundice and 145 had none. Compared with the non-jaundiced patients, the jaundiced patients had significantly longer operative time (p < 0.001) and more intra-operative bleeding (p = 0.001), frequent combined resections of adjacent organs (23.4% vs. 2.8%, p = 0.001), and postoperative complications (12.4% vs. 34%, p = 0.001). Multivariate analysis showed that preoperative jaundice was the only independent predictor of postoperative complications. The jaundiced patients had lower survival rates than the non-jaundiced patients (p < 0.001). However, lymph node metastasis and gallbladder neck tumors were the only significant risk factors of poor prognosis. Non-curative resection was the only independent predictor of poor prognosis among the jaundiced patients. The survival rates of the jaundiced patients with preoperative biliary drainage (PBD) were similar to those of the jaundiced patients without PBD (p = 0.968). No significant differences in the rate of postoperative intra-abdominal abscesses were found between the jaundiced patients with and without PBD (n = 4, 21.1% vs. n = 5, 17.9%, p = 0.787).ConclusionsPreoperative jaundice indicates poor prognosis and high postoperative morbidity but is not a surgical contraindication. Gallbladder neck tumors significantly increase the surgical difficulty and reduce the opportunities for radical resection. Gallbladder neck tumors can independently predict poor outcome. PBD correlates with neither a low rate of postoperative intra-abdominal abscesses nor a high survival rate.

The case history is described of a man in his 73rd year who was one of the oldest surviving patients with uncorrected tetralogy of Fallot (ToF) before succumbing with renal failure. Factors contributing to his longevity included small pulmonary arteries and presumed slow development of subpulmonary obstruction together with moderate concentric left ventricular hypertrophy-features previously seen in long term survivors. Less than 3% of all patients with uncorrected ToF survive beyond their 40s but late operative repair is still a valuable option. Practicalities of renal dialysis in the presence of an intracardiac shunt are considered.T etralogy of Fallot (ToF), first described in 1888, comprises an interventricular septal defect, right ventricular outflow tract obstruction, an overriding aorta, and right ventricular hypertrophy (RVH).1 It is the most common form of cyanotic congenital heart disease (10% of all cases).2 This case describes a man in his 73rd year who was one of the oldest surviving patients with an uncorrected ToF before succumbing with renal failure. We review the factors contributing to his longevity and consider whether surgery in his 66th year would have been appropriate. CASE PRESENTATIONThe patient, described as having a weak heart in childhood, never attended school or played sports. Diagnosis of ToF was not made until the age of 31 (1961) but he defaulted from further investigations. In 1996 (aged 66 years) he was reassessed while being investigated for proteinuria (urea = 5.7 mmol/l; Cr = 98 mmol/l). He was asymptomatic. He was mildly cyanosed and clubbed with pectus carinatum. Blood pressure was 140/80 mm Hg. He had an ejection systolic murmur in the pulmonary area. Echocardiography disclosed a subaortic VSD with a left to right shunt of 1.94 m/s, minimal aortic override (diameter 3.76 cm), small volume, hypertrophied well contracting LV, RVH, dilated RA, bicuspid pulmonary valve with a small pulmonary artery (1.4 cm), subpulmonary stenosis with an RVOT gradient of 112 mm Hg, and moderate PR. Electocardiography confirmed sinus rhythym, voltage criteria for RVH; RBBB with a QRS duration of 100 ms. Chest radiography showed a right aortic arch. Holter monitoring disclosed one asymptomatic 4 beat burst of SVT. Exercise testing terminated at four minutes because of fatigue (O 2 saturation fell from 91% to 80%). The decision was made for medical management rather than surgical correction in view of his advanced age, asymptomatic status, and personal wishes. At the age of 69 the patient complained of regular fast palpitations and associated dyspnoea. The echocardiogram showed severely hypertrophied and impaired RV function, huge RA (6.868.2 cm), normal LV dimensions with moderate concentric hypertrophy as before, and a dilated LA (5.82 cm). Creatinine was 118 mmol/l. He was treated with frusemide, spironolactone, amiodarone, and aspirin. His renal function deteriorated in his 72nd year (urea = 18.5 mmol/l; Cr = 174 mmol/l), and he needed thyroxine for amiodarone induced hypothyroidism. He was n...

A combination of an elevated preoperative CEA and CA19-9 was associated with a worse prognosis for patients with GBC who underwent resection.