Backgrounds/AimsDiscovery of new prognostic factors for cases in which the pancreatic cancer scoring and staging system does not result in a clear definition is imperative. We examined the role of Human AlkB homolog H5 (ALKBH5) as a prognostic marker for pancreatic cancer.MethodsPatient data were extracted from the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). The prognostic value of ALKBH5 was confirmed via analysis of ALKBH5 and other clinical factors, such as age, sex, and stage, using the time-dependent area under the curve (AUC) of Uno's C-index, the AUC value of the receiver operating characteristics (ROC) at three years, the Kaplan-Meier survival curve, and multivariate analysis.ResultsALKBH5 showed excellent prognosis prediction in comparison with existing markers in the two independent cohorts (n=262). Kaplan-Meier survival analysis showed that ALKBH5 expression was positively associated with overall survival (log-rank test, ICGC, p=0.001; TCGA, p=0.01). Notably, comparison of C-index and AUC values in ROC analysis showed that ALKBH5 was associated with high C-index and AUC values compared with other clinical variables (C-index: ICGC, 0.621; TCGA, 0.614 and AUC at three years: ICGC, 0.609; TCGA, 0.558). Multivariate analysis demonstrated thatALKBH5 is an independent prognostic factor (ICGC, p=0.0123; TCGA, p<0.001).ConclusionsThese findings contribute to the study of RNA methylation in pancreatic cancer. We believe that ALKBH5 is a new prognostic marker for pancreatic cancer.
Transjugular liver biopsy (TJLB) is an alternative method of pathological diagnosis in patients with an established contraindication to percutaneous biopsy. Between November 2005 and July 2007, 111 TJLBs were attempted in 67 patients and 95 percutaneous liver biopsies (PCLBs) were attempted in 51 patients with living donor liver transplantation suspected of having rejection. Indications of TJLB included classic contraindications to PCLB and a postoperative period of less than 30 days. TJLB was performed a mean of 111.1 Ϯ 292.6 days after transplantation (range: 6-2478 days, median: 35 days), and PCLB was performed a mean of 534.7 Ϯ 591.6 days after transplantation (range: 6-2555 days, median: 299 days). Technical success was 99.1% in TJLB and 100% in PCLB, and there was no significant difference between these 2 groups (P ϭ 0.354). A clinical suspicion of rejection was confirmed by histopathology in 38 (34.2%) of 111 TJLBs and 38 (40.0%) of 95 PCLBs. The overall complication rates related to the procedure were 1.8% (2/111) in TJLB and 5.3% (5/95) in PCLB. Although there was no significant difference in complication rates between TJLB and PCLB (P ϭ 0.172), the patients who underwent TJLB showed significantly higher incidence of ascites, coagulopathy, and thrombocytopenia, given its indication. TJLB seems to be a safe and effective procedure for pathological diagnosis of rejection in patients with living donor liver transplantation when there is a high risk of complication with PCLB. Liver Transpl 14: 971-979, 2008.
AIMTo evaluate portal vein (PV) stenosis and stent patency after hepatobiliary and pancreatic surgery, using abdominal computed tomography (CT).METHODSPercutaneous portal venous stenting was attempted in 22 patients with significant PV stenosis (> 50%) - after hepatobiliary or pancreatic surgery - diagnosed by abdominal CT. Stents were placed in various stenotic lesions after percutaneous transhepatic portography. Pressure gradient across the stenotic segment was measured in 14 patients. Stents were placed when the pressure gradient across the stenotic segment was > 5 mmHg or PV stenosis was > 50%, as observed on transhepatic portography. Patients underwent follow-up abdominal CT and technical and clinical success, complications, and stent patency were evaluated.RESULTSStent placement was successful in 21 patients (technical success rate: 95.5%). Stents were positioned through the main PV and superior mesenteric vein (n = 13), main PV (n = 2), right and main PV (n = 1), left and main PV (n = 4), or main PV and splenic vein (n = 1). Patients showed no complications after stent placement. The time between procedure and final follow-up CT was 41-761 d (mean: 374.5 d). Twenty stents remained patent during the entire follow-up. Stent obstruction - caused by invasion of the PV stent by a recurrent tumor - was observed in 1 patient in a follow-up CT performed after 155 d after the procedure. The cumulative stent patency rate was 95.7%. Small in-stent low-density areas were found in 11 (55%) patients; however, during successive follow-up CT, the extent of these areas had decreased.CONCLUSIONPercutaneous transhepatic stent placement can be safe and effective in cases of PV stenosis after hepatobiliary and pancreatic surgery. Stents show excellent patency in follow-up abdominal CT, despite development of small in-stent low-density areas.
Background/Aims: To analyze the incidence and risk factors of outcomes after liver transplantation (LT) in the Korean population. Methods: This study analyzed data from the liver cohort of Korean Organ Transplantation Registry (KOTRY) who had LT between May 2014 and December 2017. Study measures included the incidence of post-LT outcomes in recipients of living donor LT (LDLT) and deceased donor LT (DDLT). Cox multivariate proportional hazards model was used to determine the potential risk factors predicting the outcomes. Results: A total of 2,563 adult recipients with LT (LDLT, n=1,956; DDLT, n=607) were included, with mean±SD age of 53.9±8.9 years, and 72.2% were male. The post-LT outcomes observed in each LDLT and DDLT recipients were death (4.0% and 14.7%), graft loss (5.0% and 16.1%), rejection (7.0% and 12.0%), renal failure (2.7% and 13.8%), new onset of diabetes (12.5% and 15.4%), and hepatocellular carcinoma (HCC) recurrence (both 6.7%). In both LDLT and DDLT recipients, the most common post-LT complications were renal dysfunction (33.6% and 51.4%), infection (26.7% and 48.4%), and surgical complication (22.5% and 23.9%). Incidence of these outcomes were generally higher among recipients of DDLT than LDLT. Multivariate analysis indicated recipient age and DDLT as significant risk factors associated with death and graft loss.DDLT and ABO incompatible transplant were prognostic factors for rejection, and HCC beyond Milan criteria at pre-transplant was a strong predictor of HCC recurrence. Conclusions: This study is a good indicator of the post-LT prognosis in the Korean population and suggests a significant burden of post-LT complications.
Inhibitors of histone deacetylases (HDACs) have been shown to induce differentiation and/or apoptosis of human tumor cells. Novel 3-(4-substituted-phenyl)-N-hydroxy-2-propenamides have been prepared as a new class of HDAC inhibitors and evaluated for their antiproliferative activity and HDAC inhibitory activity. Incorporation of a 1,4-phenylene carboxamide linker, shown by 5, and a 4-(dimethylamino)phenyl or 4-(pyrrolidin-1-yl)phenyl group as a cap substructure generated highly potent hydroxamic acid-based HDAC inhibitors 5a and 5b.
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